1. science
2. medicine
3. surgery

Treatment of Gallstone patients
In the Danish health care system, more than DKK 100 million per year are
spent on treating patients with benign biliary tract diseases.
This report is the first attempt at performing a health technology
assessment of treatment of gallstone patients. By including the technology,
the patient, the organisation as well as the economy, a health technology
assessment is an analytical tool that serves as basis for ensuring an optimal
treatment of patients within the given economical framework.
The report is based on a systematic review of the literature and a
thorough analysis of data from The National Hospital Register where all
hospital admissions in Denmark are recorded. By reviewing the literature
using explicit criteria, the fundament for performing an objective assessment
of the various treatment modalities has been established. At the same time,
analyses of data from The National Hospital Register form a clear picture of
the development of treatment of gallstone patients throughout Denmark.
By combining the technology with the economical analyses, the limited
knowledge of patients’ preferences for the various treatment modalities
as well as the organisational aspects, the report questions a number of
well-established treatment modalities and the organisation of these.
It is the hope, that this report will form part of a knowledge-based
fundament for the development of a national strategy for prevention,
diagnosis and treatment of patients with biliary tract disease.
Torben Jørgensen
Treatment of
Gallstone
patients
A health technology assessment
Counselling and advising in connection with HTA projects is given by:
Danish Institute for Health Technology Assessment
National Board of Health
13, Amaliegade
PO. Box 2020
DK-1012 Copenhagen
Denmark
Phone: + 45 33 91 16 01
Fax: + 45 33 91 70 61
E-mail: [email protected]
Homepage: http://www.dihta.dk
Further copies of this publication can be bought at:
Sundhedsstyrelsens Publikationer
c/o Schultz Information
12, Herstedvang
DK-2620 Albertslund
Denmark
Phone: + 45 70 26 26 36
Fax: + 45 43 63 62 45
NIPH & Danish Institute for Health Technology Assessment 2000
National Institute of Public Health
25, Svanemøllevej
DK-2100 Copenhagen , Denmark
Phone: +45 39 20 77 77
Fax: +45 39 20 80 10
E-mail: [email protected]
Homepage : www.dike.dk
Danish Institute for
Health Technology Assessment
D I T H A
Torben Jørgensen
2000
Treatment of
Gallstone
patients
A health technology assessment
Danish Institute for
Health Technology Assessment
D I H T A
TREATMENT OF GALLSTONE PATIENTS
A health technology assessment
ISBN (printed version): 87-90951-44-1
ISBN (electronic version): 87-7676-381-1
© Torben Jørgensen
Copenhagen 2000
Published by:
National Institute of Public Health
25, Svanemøllevej
DK-2100 Copenhagen, Denmark
Phone: + 45 39 20 77 77
Fax: + 45 39 20 80 10
E-mail: [email protected]
Homepage: www.dike.dk
and
Danish Institute for Health Technology Assessment
National Board of Health
13, Amaliegade
PO. Box 2020
DK-1012 Copenhagen
Denmark
Phone: + 45 33 91 16 01
Fax: + 45 33 91 70 61
E-mail: [email protected]
Homepage: http://www.dihta.dk
Layout: Peter Dyrvig Grafisk Design
Print: P.J. Schmidt A/S, Vojens
Production: Danish Committee for Health Education
Printed witout solvents, using only natural vegetable colours,
on environmentally approved paper.
Further copies of this publication can be bought at:
Sundhedsstyrelsens Publikationer
c/o Schultz Information
12, Herstedvang
DK-2620 Albertslund
Denmark
Phone: + 45 70 26 26 36
Fax: + 45 43 63 62 45
Cover photo: Professor Carl Langenbuch, who in Berlin in 1882 carried out the first cholecystectomy.
2
Institutional foreword
This report started as a joint clinical epidemiological project involving the
National Institute of Public Health (NIPH) and consultant surgeon Torben Jørgensen during his tenure in the Surgical Department at Bispebjerg
Hospital. The NIPH has traditionally been adept at analysing data from
the National Hospital Discharge Register for health service research projects and health technology assessments. Torben Jørgensen has a longstanding interest in gallstone epidemiology and has conducted critical research into surgical treatment of gallstones. Torben Jørgensen worked at
the NIPH during part of the project and it was finished after his appointment as head of the Copenhagen County Centre of Preventative Medicine,
Glostrup University Hospital.
The project was financed by the NIPH’s basic grant and the Health Insurance Fund
It was decided that the appropriate form for the project was a health
technology assessment (HTA), i.e. an assessment in which clinicians, epidemiologists, statisticians and health service economists co-operate to
study a particular clinical field.
Due to the current heavy interest in HTA projects, it was agreed with
the Danish Institute for Health Technology Assessment (HTA Institute)
that we would finance the expansion of the project to encompass health
economics and organisational elements, etc. As a result of this decision,
co-operation was also established with the health service economists at
the Centre for Health and Social Policy, University of Southern Denmark.
In other words, the project has grown from a somewhat narrow clinical epidemiological project to a project that aspires to the breadth of an
HTA. The emphasis in the report is, however, still on the clinical and epidemiological areas.
NIPH and the HTA Institute found it appropriate to co-operate on the
publication of the overall HTA report. The report will be supplemented
by scientific articles in magazines in Danish and English.
For further details, please refer to the author’s foreword.
Finn Kamper-Jørgensen, Director
National Institute of Public Health
Finn Børlum Kristensen, Head of Institute
Danish Institute for Health Technology Assessment
3
Author’s foreword
The idea for this report emerged during my tenure as consultant in the
Surgical Gastroenterology Ward K at Bispebjerg Hospital in Copenhagen.
It started out as a clinical epidemiological project and as a natural progression of my research into biliary tract disorders. During the preliminary research, it became evident that the whole area was crying out for indepth study, hence the decision to expand the project into a health technology assessment in order to lay the foundations for the rational, patientfriendly and economical treatment of patients with biliary tract disorders.
The concept was presented at a meeting of Dansk Kirurgisk Selskab
(Danish Society of Surgeons) in spring 1997 and the Society expressed the
wish that the report would form the basis for national clinical guidelines.
In order to include a maximum number of aspects of the treatment of
biliary tract disorders, the report has become very comprehensive. As a result, those with no knowledge of the field will find the report heavy reading. Chapters 1-4 ought to be read, while chapters 5-8 can be read separately or used for reference purposes, as they concern particular aspects of
biliary tract disorder. Chapters 9, 10 and 11 cover the other aspects of an
HTA: the patient, the organisation and the finances. As so much documentation has been included, some of it has been included in appendices,
which can be read as required. The summary (chapter 12) and the synthesis and recommendations (chapter 13) can be read on their own.
A number of people have contributed to this report. Firstly, I would
like to thank chief surgeon Johan Kjærgaard for his willingness to grant
me leave for seven months, for all our in-depth discussions and for his
willingness to read and comment critically on the report. I would also like
to thank my ex-colleague in department K, development consultant Ingrid
Willaing for our fruitful discussions as well as her stringent and always
positive critical study of my draft manuscript.
The work was done at the National Institute for Public Health, which
possesses the necessary expertise in the processing and analysis of data
from the National Hospital Discharge Register. Director Mette Madsen,
MA, NIPH provided invaluable help interpreting and analysing data from
the National Hospital Discharge Register and discussing and revising the
report critically. IT consultant Lene Bjørk Nielsen, NIPH was responsible
4
for the huge task of transforming the data from the National Hospital Discharge Register into a form that can be analysed and Søren Rasmussen,
MSc, NIPH, performed the statistical analyses in exemplary fashion and
wrote appendix 4 of this report. Health economist Jørgen Clausen from
CHS at the University of Southern Denmark did a marvellous job being
responsible for the financial analyses. Jørgen Clausen’s detailed financial
analyses form the basis for chapter 11 and enclosure 5 in the report. I
would like to avail myself of this opportunity to thank them all for their
positive and constructive co-operation.
I would also like to thank the many surgical and medical departments
all over the country who worked long and hard in attempt to validate the
National Hospital Discharge Register and to assess the time and staff demands of the different surgical and endoscopic operations. Thanks are
due to secretary Margit Christiansen, NIPH, for all her work sending out
and sorting questionnaires and medical commentaries. I would also like to
express my gratitude to Anne Eliasen, medical student Sine Wanda Jørgensen, and medical student Jette Nielsen for all their help with the medical commentaries. Thanks are also due to Sine Wanda Jørgensen for her
patience and stamina photocopying the many thousands of articles upon
which the report is based. Secretary Ulla Jørgensen deserves a special
thank you for her assiduous proof-reading and ward doctor Dina Hauge
for her translations of Italian articles.
Finally, I would like to express my sincere gratitude to Director Finn
Kamper-Jørgensen and the staff of NIPH for providing a positive, hospitable and inspiring working environment.
The work was financed in part by the Health Insurance Fund (11/24995) and the Danish Institute for Health Technology Assessment (J.no.
3126-2-1997).
NIPH, 4 December 1998
Torben Jørgensen
Note: This report was translated from Danish by “The Translation Centre,
University of Copenhagen”.
5
Content
1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .9
1.1
1.2
1.3
Gallstones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .9
1.1.1 Occurrence of gallstones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .9
1.1.2 Who has gallstones? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .9
1.1.3 The disease spectrum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .11
Developments in the treatment of gallstone patients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .11
1.2.1 Cholecystectomy (removal of the gallbladder) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .12
1.2.2 Cholecystolithotomy (removal of gallbladder stone) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .13
1.2.3 Bile salts and ESWL (medical dissolution of gallstones) . . . . . . . . . . . . . . . . . . . . . . . . . . . . .14
1.2.4 Choledocholithotomy (removal of stones in the bile duct) . . . . . . . . . . . . . . . . . . . . . . . . . . .14
Health technology assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .16
2. Material and methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .19
2.1
2.2
2.3
2.4
2.5
2.6
The National Hospital Discharge Register . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .19
2.1.1 Courses of treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .19
2.1.2 The validity of the National Hospital Discharge Register . . . . . . . . . . . . . . . . . . . . . . . . . . . .22
Literature . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .24
Danish population studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .25
Staff and staff time in the treatment of gallstone patients in Denmark . . . . . . . . . . . . . . . . . .25
The National Register for Laparoscopic Cholecystectomy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .25
Analyses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .26
3. Occurrence, natural history and prevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .28
3.1
3.2
3.3
Gallstone disorders in the Danish population . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .28
The natural history of people with untreated gallstones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .29
Prevention of gallstones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .30
3.3.1 Primary prevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .30
3.3.2 Secondary prevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .31
4. Treatment of patients with benign biliary tract disorders in Denmark 1978-95 . . . . .33
5. Treatment of patients with non-complicated gallbladder stones . . . . . . . . . . . . . . . . .47
5.1
5.2
5.3
5.4
6
Developments in Denmark, 1978-95 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .47
5.1.1 The frequency of simple cholecystectomy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .47
5.1.2 Regional variations in Denmark . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .51
Which symptoms are due to stones in the gallbladder? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .60
Indication for treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .63
Methods of treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .66
5.4.1 Cholecystectomy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .66
5.4.2 Cholecystolithotomy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .86
5.4.3 ESWL/bile salts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .87
5.4.4 Comparison between cholecystectomy, cholecystolithotomy and ESWL/bile salts . . . . . .89
5.4.5 Cholecystectomy for acalculous pains . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .90
6. Treatment of patients with acute cholecystitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .92
6.1
6.2
6.3
Developments in Denmark 1978-95 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .92
Indication for treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .95
Methods of treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .95
6.3.1 Cholecystectomy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .95
6.3.2 Cholecystolithotomy and partial cholecystectomy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .98
6.3.3 Ultrasonic drainage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .98
6.3.4 Acalculous cholecystitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .99
7. Treatment of patients with choledochal stones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .100
7.1
7.2
7.3
Developments in Denmark, 1978-95 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .100
Indication for examination and treatment of stones in the bile ducts . . . . . . . . . . . . . . . . . . .104
Methods of treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .106
7.3.1 Surgical methods of treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .107
7.3.2 Endoscopic methods of treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .107
7.3.3 Comparison between surgical and endoscopic treatment . . . . . . . . . . . . . . . . . . . . . . . . . .108
7.3.4 Thirty-day mortality rates in Denmark, 1978-95 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .109
8. Treatment of patients with gallstone pancreatitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . .111
8.1
8.2
8.3
Development in Denmark, 1978-95 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .111
Indication for treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .111
Methods of treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .111
8.3.1 Cholecystectomy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .112
8.3.2 Endoscopic treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .113
8.3.3 Treatment strategies for gallstone pancreatitis – summary . . . . . . . . . . . . . . . . . . . . . . . .113
9. The patient . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .115
9.1
9.2
9.3
9.4
The patient’s choice of treatment procedure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .115
Patient expectations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .116
Patient information . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .116
The patient’s assessment of the given treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .117
10. Organisation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .119
10.1 Administrative rules for the treatment of patients with gallstones in Denmark . . . . . . . . . .119
10.2 Gallstone treatments in Denmark . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .119
10.2.1 Developments in Denmark, 1978-95 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .119
10.2.2 Morbidity and mortality in relation to the number of operations . . . . . . . . . . . . . . . . . . .120
10.3 Training for gallstone surgeons . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .120
11. Economy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .123
11.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .123
11.2 Developments in treatment costs in Denmark, 1978-1995 . . . . . . . . . . . . . . . . . . . . . . . . . . . .124
11.2.1 All treatments for benign biliary tract disorderse . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .124
11.2.2 Simple cholecystectomy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .126
11.2.3 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .127
11.3 Economical models for gallstone treatments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .128
11.3.1 Treatment of patients with stones in the gallbladder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .129
11.3.2 Treatment of patients with acute cholecystitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .140
11.3.3 Treatment of patients with stones in the bile ducts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .141
7
12. Summary of the elements in the Health Technology Assessment . . . . . . . . . . . . . . . .142
12.1 Developments in the incidence and treatment of gallstones . . . . . . . . . . . . . . . . . . . . . . . . . . .142
12.2 Material and methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .144
12.3 Occurrence, natural history and prevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .145
12.4 Overall treatment of biliary tract disorders in Denmark . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .146
12.5 Treatment of patients with uncomplicated gallbladder stones . . . . . . . . . . . . . . . . . . . . . . . .147
12.6 Treatment of patients with acute cholecystitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .151
12.7 Treatment of patients with stones in the bile ducts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .152
12.8 Treatment of patients with gallstone pancreatitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .154
12.9 The patient . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .154
12.10 The organisation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .155
12.11 Economy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .156
13. Synthesis and recommendations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .158
Appendices
1
2
3
4
5
8
Literature list . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .164
The National Hospital Discharge Register . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .201
Extract from the National Hospital Discharge Register . . . . . . . . . . . . . . . . . . . . . . . . . . . . .201
Validation of the National Hospital Discharge Register . . . . . . . . . . . . . . . . . . . . . . . . . . . .209
Developments in the use of different technologies for treatment of patients
with bile duct disorders, 1978-95 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .210
Literature . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .214
Search of literature . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .214
Critical evaluation of the literature . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .215
Selected literature . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .217
Statistical analyses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .236
Analysis of developments in surgical rate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .236
Regional variations in operation rates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .241
Analyses of 30-day mortality rates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .244
Analyses of complicated courses of treatment in cases of simple cholecystectomy . . . . .245
The distribution of municipalities between admissions areas . . . . . . . . . . . . . . . . . . . . . .246
Economical analyses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .250
Costs of gallstone treatment in Denmark . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .250
Sensitivity analyses of the economical models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .254
1. Introduction
1.1
G ALLSTONES
1.1.1 Occurrence of gallstones
Gallstones are probably as old as mankind. Gallstones were found in an
Egyptian mummy (21st dynasty, approx. 1000 BC) and the description of
Alexander the Great’s final days (323 BC) suggests that he may have died
of acute infection of the gallbladder73. Gallstones were probably described
for the first time ever by a 6th century Greek doctor. Since anatomical dissection was introduced in 1281 in Italy, gallstones have been identified
with increasing regularity73. Danish autopsies around the turn of the
19th/20th century revealed gallstones in 24-33% of 60-70-year-old
women and 16-25% of 60-70-year-old men306, 346, 683 which corresponded
to rates in the rest of Europe110. In the first decade after the Second World
War, occurrence of gallstones increased in Denmark, followed by a fall up
till the mid-80s770, 771.
Today, gallstones are a common occurrence in large parts of the world184,
373
. The prevalence is greatest on the American continent with Chileans the
most prominent group158, followed by Europe, where Norway276 and the
ex-GDR83 have the highest rates. In Russia639 and North India395 the rates
correspond to Europe, while they are very low in south-east Asia and
Africa408, 465, 859, 861. Figures 1-4 show incidences of gallstones in a number
of populations in the 1980s.
1.1.2 Who has gallstones?
Gallstones are formed from chemical substances in the bile. The most common type is the cholesterol stone, which consists of cholesterol and bile
salts. Pigment stones, which consist of calcium and bile pigment (bilirubin)
are less common362. A number of epidemiological surveys have identified
the most important risk factors related to gallstones184, 373, 676. Women
suffer from gallstones twice as often as men, mainly because of pregnancies366, 375. Overweight individuals are more susceptible to gallstones than
people of standard weight369, while exercise and moderate alcohol
consumption reduce the chances of gallstones development369, 374, 775. There
seem to be a familial aggregation of gallstones61, 367, 572 and the most recent
research suggests that people with insulin resistance (a metabolic condition
9
FIGURE 1
Prevalences of gallstones in
European populations. Women
100
FIGURE 2
Prevalences of gallstones in
European populations. Men
Prevalence %
100
90
90
80
80
70
Prevalence %
70
4
60
60
6
50
2
1
40
40
7
30
3
20
10
FIGURE 3
Prevalences of gallstones in
non-European populations. Women
FIGURE 4
Prevalences of gallstones in
non-European populations. Men
Prevalence %
100
90
80
80
Prevalence %
70
1
60
60
50
50
2
40
40
30
30
20
20
4
3
6
5
0
10
0
0 10 20 30 40 50 60 70 80 Age
1. Chile158, 2. USA (Mex-Am)304, 3. USA (Puerto Rico)492,
4. India (Kashmir)395, 5. Japan566, 6. Taiwan859
10
0 10 20 30 40 50 60 70 80 Age
1. Norway276, 2. Sweden352,511,539, 3. Denmark365,375,
4. GDR83, 5. U.K.315, 6. Italy53
90
10
3
5
0
0 10 20 30 40 50 60 70 80 Age
1. Norway276, 2. Sweden352,511,539, 3. Denmark365,375,
4. GDR83, 5. U.K.315, 6. Czechoslovakia86, 7. Italy53
70
6
2
10
0
100
4
1
30
5
20
50
1
2
3
5
6
4
0 10 20 30 40 50 60 70 80 Age
1. Chile158, 2. USA (Mex-Am)304, 3. USA (Puerto Rico)492,
4. India (Kashmir)395, 5. Japan566, 6. Taiwan859
that increases the risk of arteriosclerosis, cardiovascular disease, obesity
and non-insulin-dependent diabetes) have a far higher occurrence of gallstones than non-insulin-resistant372. This corresponds to the very high
incidence of gallstones among Native Americans, the majority of whom
are insulin resistant677. Gallstones are rarely encountered in children and
young people, but the prevalence increases with age585, 832.
1.1.3 The disease spectrum
Gallstone disease is a chronic condition, which starts - and usually ends
- as an asymptomatic condition, i.e. a condition that the person never discovers. The development is probably as follows:
❖
Stones are formed in the gallbladder, where they remain asymptomatic for a long
time, perhaps permanently. Small gallstones can disappear again spontaneously.
❖
Stones can cause pain, which is unpleasant, but not dangerous.
❖
After an certain number of years, the stones can cause complications, which as a
rule can be easily treated and are rarely life-threatening:
- Acute cholecystitis
- Choledochal stone
Icterus/cholangitis
Acute pancreatitis
- Fistulation, if a chronic infection involves the neighbouring organs.
1.2
D EVELOPMENTS IN THE TREATMENT OF GALLSTONE PATIENTS
Doctors did not attribute any significance to gallstones in relation to
symptoms such as abdominal pains, jaundice and infection until the 16th
century73. In principle, there are two methods of treating stones in the
gallbladder:
❖
Removal of the gallbladder including the stone (cholecystectomy)
❖
Removal of the stone from the gallbladder
- invasive technique (cholecystolithotomy or contact dissolution)
- non-invasive technique (ESWL/bile salts). .
In principle stones in the bile duct should be removed (choledocholithotomy). Below is a short description of historical developments in the different forms of treatment.
11
1.2.1 Cholecystectomy (removal of the gallbladder)
Three different technologies are used: traditional open cholecystectomy,
cholecystectomy by minilaparotomy and laparoscopic cholecystectomy.
The first cholecystectomy was performed by Langenbuch in Berlin in
1882429, while the first cholecystectomy in Denmark was performed in
1887 by Iversen at Copenhagen District General Hospital25. Removal of
gallbladder and stones remains the standard treatment to this day. The
gallbladder was removed through a 10-20 cm long subcostal or vertical
midline incision (traditional open cholecystectomy). The argument in
favour of the large incision was that it afforded the surgeon a better view
and that the whole of the abdominal cavity could be properly examined.
In the early 70s, a technique was developed in which the surgeon uses
long instruments to remove the gallbladder through a 3-6 cm long incision
and does not insert his hands into the abdomen (cholecystectomy by minilaparotomy)197, 282. The argument in favour of minilaparotomy is that it reduces surgical trauma and, consequently, the time spent in hospital and
the convalescence period (the period from the operation to resumption of
work/normal activities). It is difficult to define exactly which incisions
qualify as traditional laparotomy and which constitute minilaparotomy.
Besides the length of the incision, it has been discussed whether the procedure also should spare the muscles (i.e. not separate the muscles in the
abdominal wall) before it can be defined as minilaparotomy. The majority defines an operation as minilaparotomy if the incision is under 6 cm,
while others accept 8 cm483, 656 or even 10 cm435, 504. Some point out the importance of the location of the incision, which ought to be on the right of
the epigastrium, just above the point where ductus cysticus joins ductus
choledochus. This is where the difficult dissection occurs793. If a minilaparotomy runs into technical or other problems, the incision is lengthened
and the operation is converted into a traditional open cholecystectomy. It
is uncertain, when the first cholecystectomy during a minilaparotomy was
performed in Denmark733.
Mühe introduced laparoscopic cholecystectomy in Germany in 1985545,
546
. The method was refined by Mouret in France in 1987198, 601. The operation is performed with special instruments and video equipment inserted through three or four trochars (“doors”) in the abdominal wall,
each 1⁄2-1 cm in diameter. Thus, the total incision is 3-4 cm. The arguments
in favour of laparoscopic cholecystectomy correspond to those in favour
of cholecystectomy by minilaparotomy: it reduces surgical trauma, the
time spent in hospital and the convalescence period. If technical or other
12
difficulties occur, the operation is converted into open surgery – usually
traditional open cholecystectomy. This requires new instruments, a new
incision and the removal of old instruments. Outside Denmark, the laparoscopic technique soon gave cause for concern because of a suspected
rise in the number of bile duct lesions166 and at the same time, the number
of gallstone operations increased149. Laparoscopic cholecystectomy was
introduced to Denmark in January 1991. During the first year, only a
small proportion of the total number of cholecystectomies were performed laparoscopically, but in the ensuing year the number increased to
constitute the majority.
1.2.2 Cholecystolithotomy (removal of gallbladder stone)
Surgical removal
In 1667, an abscess in the abdominal wall containing a gallstone was emptied322. It is probably the first recorded case of cholecystolithotomy as a
treatment for acute infection of the gallbladder. The first planned operation to remove a stone from a gallbladder was performed by Bobbs in
1867 in the USA169. When Langenbuch later carried out the first cholecystectomy, most surgeons converted to removal of the gallbladder along
with the stones due to the large number of patients who experienced a recurrence of their gallstones after cholecystolithotomy603. Langenbuch is
quoted as saying: “The gallbladder has to be removed – not because it
contains stones, but because it generates stones.” Cholecystolithotomy
still had its advocates, however, and as late as World War Two many surgeons in Denmark insisted on removing only the gallstones25, 603. Already
in 1955 it was described that the procedure could be performed by minilaparotomy670 and even under local anaesthesia645 for patients unable to
tolerate general anaestesia. Later, a laparoscopic method was developed in
which a scope is inserted through a 2-3 cm incision, attaches itself to the
gallbladder using suction, opens the gallbladder and empties it of stones434,
481
. This operation can also be performed under local anaesthesia. The development of ultrasound techniques made it possible to puncture the gallbladder. In the beginning, this method was used on patients with acute
cholecystitis to combat infection in advance of subsequent operations623.
The latter method was further refined by dilating the puncture canal and
inserting instruments to remove the stones or laser/ultrasound probes to
pulverise the stones16, 341, 386, 392, 833. The method has been used in Denmark734.
13
Contact dissolution
Since the 19th century, it has been a well-known fact that ether dissolves
gallstones814. Methyl tertbutyl ether (MTBE) has been particularly well researched because it stays in liquid form at body temperature (boiling point
55). MTBE is injected via a catheter guided into the gallbladder by ultrasound equipment22. It can take from a few hours to a couple of days to dissolve the stones and flush them out207, 318. The method is described in depth
by Thistle777. Attempts have been made to combine the method with
ESWL (see next section)562, 597 and other solvents351, 553 – but to no great effect. Often, the procedure is followed up with bile salts193. Instead of percutaneous (and therefore invasive) incision, reports have been published
of inserting a naso-biliary catheter into the gallbladder by ERCP and dissolving gallbladder stones with MTBE234. MTBE has a number of side effects in the form of lethargy and nausea. Recently, positive tests have been
performed using ethyl propionate without the side effects of MTBE. However, the tests only comprised five patients330. It is not known to what extent the method has been tried in Denmark.
1.2.3 Bile salts and ESWL (medical dissolution of gallstones)
Bile salts reduce cholesterol concentration in the bile331. The first attempt
to dissolve gallstone with bile-salt treatment was performed in 1970171 using chenodeoxycholic acid, but the initial results were not promising691,
partly because of side-effects such as diarrhoea, liver damage and increased levels of cholesterol in the blood254. In 1975, a new chemical was
launched on the market (ursodeoxycholic acid), which was more efficient
and had fewer side effects430, 672. Treatment with bile salts takes several
months to years485.
In 1985, bile salt treatment was combined with ESWL (Extracorporeal
ShockWave Lithotripsy)680, which uses sound waves to pulverise gallstones. ESWL produces a blast wave that works in fluids. A targeting system makes sure that the blast wave hits the gallstones and does not cause
lesions to the surrounding tissue. This combination of bile salts and ESWL
has been used in Denmark31, 47.
1.2.4 Choledocholithotomy (removal of stones in the bile duct)
Stones in the bile duct almost always stem from the gallbladder. Surgical
removal of stones in the bile duct was done for the first time by Courvoisier in Basle in 189073. From then on, open surgery to remove the gallbladder and the stones in the bile duct (traditional open bile duct surgery)
14
became the standard treatment. Often, patients do not have bile duct
stones diagnosed until they are X-rayed during the operation (intraoperative cholangiography). Sometimes the number of number or size of bile
duct stones is so great, or the alterations of the bile duct so severe, that it
has to be dissected and sewn onto the intestines (biliodigestive anastomosis). A 1978-85 Danish survey revealed that 20% of patients who underwent cholecystectomy also had stones removed from ductus choledochus
and a further 5% underwent biliodigestive anastomosis106. Open bile duct
surgery has traditionally been performed through a 10-20 cm long subcostal or vertical midline incision. In 1982, the first report was published
concerning the removal of stones in the bile duct through a small incision
of 4-5 cm (removal of bile duct stone through minilaparotomy)197, 532. In
1991, the first report340 was published concerning removal of stones from
the bile duct with the help of laparoscopic surgery (laparoscopic removal
of stones from the bile duct). The latter method has not been adopted in
Denmark37.
The first ERCP (Endoscopic Retrograde Cholangiopancreatography)
was presented in 1970575. Later, instruments were developed to perform
sphincterotomy and remove stones from the bile duct143, 383. ERCP was introduced to Denmark in 1973412, 413, 491, but initial progress was slow. In
the late 80s, the pace at which ERCP technology spread began to pick up
and then accelerate after the introduction of laparoscopic cholecystectomy in 1991. As ERCP technology was developed, so was a number of
other treatments for stones in the bile duct, e.g.: contact dissolution156, direct dissolution by introduction of various medicaments into the bile
duct544 and ESWL738. The latter method is used in Denmark24. In cases,
where it proved impossible to remove the gallstones, methods were developed to insert a drain and allow the bile to pass125. Instead of a sphincterotomy, proposals have been mooted to dilate the sphincter with a balloon and then remove the stones474.
Recently, MR scanning (magnetic resonance), which unlike ERCP is a
non-invasive technique, has been used to produce a three-dimensional image of the biliary tracts (MRC) and the results have been promising727.
1.3
H EALTH TECHNOLOGY ASSESSMENT
Health technology assessment is defined by the Danish National Board of
Health as an all-round, systematic evaluation of the preconditions for, and
the consequences of, using health technology. Health technology includes
all forms of diagnostics, prevention, treatment and care of patients, which
15
means that it is not necessarily associated with technical equipment. In recent years, health technology assessment has gained a foothold in a number of health services all over the world. This development has coincided
with rapid technological progress within the health service, demands from
patients and health-service personnel for evidence-based treatment, plus
limited financial resources within the health sector. Patients have benefited
from many new technologies, but new technology cannot always be
equated with improved treatment.
In most fields, the supply of health technology exceeds the health service’s financial resources. In principle, this means that all new technology
ought to be subjected to health technology assessment. Health technology
assessment is, therefore, a tool that analyses all the available data and
reaches decisions about which forms of health technology are expedient
within the health service. Thus, a health technology assessment is not a
ready-made checklist of the extent to which a particular type of technology should be used and how, but a basis upon which health-service staff,
administrators and politicians can make decisions.
Ideally, the HTA process includes the five steps, illustrated in figure 5.
FIGURE 5
The five steps involved in health technology assessment
Problem identification
Planning
Technology
Analysis of the elements
Patient
Organisation
Economy
Summary
Presentation and communication
The content of the four traditional main elements in a health technology
assessment: the technology, the patient, the organisation and the finances, are described in figures 6-934.
Justification for a health technology assessment of the gallstone field
The many new methods of treatment developed in the 70s and 80s were introduced both abroad and in Denmark after trial runs in clinical series. Randomised studies of the relevance of the technologies in comparison to one another or to traditional methods of treatment were rarely conducted. The num-
16
FIGURE 6
FIGURE 7
The Technology
The Patient
Area of application
◆ What are the indications?
◆ Is there consensus on the indication?
◆ How many patients are involved?
◆ What are the relevant alternatives?
◆ Is the technology a substitute or
supplement to existing technologies?
Effectiveness
◆ Is there a documented effect?
◆ Is it more effective than the alternatives?
◆ Can the documented effect be attained in
daily practice?
Risk assessment
◆ Are there any undesired effects?
◆ Does the risk bear a reasonable
proportional relationship to the gain?
Psychological aspects
◆ Does the patient receive an optimal level
of information?
◆ Is insecurity created/experienced?
◆ Is discomfort or anxiety created/
experienced?
Effect aspects
◆ How are the effects and side-effects
perceived?
Social aspects
◆ Will it affect daily life?
◆ Will it affect employment capacity?
Ethical aspects
◆ Is the technology acceptable to the
individual patient?
◆ Is it acceptable to society?
◆ Are there special ethical issues?
FIGURE 8
FIGURE 9
The Organisation
The Economy
Structure
◆ Should the technology be centralised to a
single or a few centres?
◆ Is decentralisation possible?
◆ Will it affect the division of work between
hospital and primary healthcare?
◆ Will new specialised functions emerge?
◆ Will it change visitation criteria?
Staff
◆ Will it affect work routines?
◆ Will it affect the division of work among
professional groups?
◆ Is supplemental/developmental staff
training needed?
◆ Are there any consequences for the staff in
terms of employment?
Environment
◆ Is there an environmental risk within the
workplace?
◆ Is there a risk to the external environment?
Social and health economic appraisal
◆ What are the costs and benefits for
society?
◆ In comparison to the alternatives,
does the gain justify the effort?
◆ Is there a demonstrable health gain?
Operational economic appraisal
◆ What are the investment and operational
costs?
◆ Are there any possible cost-savings or
income generation?
◆ Who is the immediate purchaser?
◆ What accounts are affected?
◆ Are there any economic consequences for
the patient?
17
ber of new treatments has been particularly high for gallstone complications
(acute cholecystitis and bile duct stones).
Several reports have cast doubt on the benefit of introducing laparoscopic
cholecystectomy, which is expensive, may have lowered the threshold for operation and may have increased the number of serious complications during
biliary tract surgery194, 489. In addition, a number of randomised surveys have
raised doubts about the value of ERCP in relation to open surgery as treatment of stones in the bile duct394, 557, 737, 748.
Under these circumstances, the author, in collaboration with National Institute of Public Health (NIPH) and the Danish Institute for Health Technology Assessment, found it relevant to perform a health technology assessment
of the whole gallstone field. On the basis of this HTA report, national guidelines (reference programmes) can be developed for diagnostics, prevention
and treatment of gallstones.
18
2. Material and methods
2.1
T HE N ATIONAL H OSPITAL D ISCHARGE R EGISTER
Each person living in Denmark has a unique 10-digit person number,
which follows him throughout life. The person number is used for all registrations in Danish registers, which makes linkage across time and registers highly accurate.
2.1.1. Courses of treatment
Data from the National Hospital Discharge Register was used to acquire
an overall impression of developments in the treatment of patients with
gallstones in Denmark in the period 1978-95. A total of 99,803 hospital
admissions were identified, including 87,007 patients of relevance to this
report (see enclosure 2). As a rule, a patient’s treatment for gallstones is
completed during a single stay in hospital, but sometimes a patient is admitted several times during the same course of his or her treatment, partly
for diagnostic examinations (ERCP), partly because the treatment is complicated and complications arise during it. In order to identify these
courses of treatment, all hospital admissions for biliary tract treatment
listed under the same patients person number with less than a year between discharge date and subsequent admission date have been considered as a single course of treatment. A single patient may have undergone
several courses of treatment. For the 87,007 patients, 90,582 courses of
treatment were identified - 96.3% of the patients underwent only a single
course of treatment, 3.2% underwent two, while 0.4% underwent three
or more. The treatments have been divided into a number of clinically relevant groups according to the index admission that refers to the primary
treatment (the index treatment). This included the following index admissions (table 1).
Simple cholecystectomy
These patients, who make up the vast majority of cases, had their gallbladders removed because of pains or infection. The majority of these patients were admitted once only.
19
Cholecystectomy plus endoscopic bile duct treatment during the same
stay in hospital
These patients had the gallbladder as well as stone from the bile ducts
removed during the first course of treatment or experienced complications
during the primary cholecystectomy that were treated endoscopically during the same stay in hospital.
Cholecystectomy plus open bile duct surgery during the same stay in
hospital
Most of the patients in this group had their gallbladder and stones in the
bile duct removed. The group also includes patients whose choledochus
was examined in greater detail during the operation (explorative choledochotomy), or who suffered a lesion of the choledochus that was diagnosed and treated during the same stay in hospital.
Cholecystectomy with biliodigestive anastomosis
This group consists mainly of patients with stones in both the gallbladder
and the bile duct and whose bile duct was altered to such an extent that
the surgeon deemed it necessary to perform an anastomosis of the bile
duct and intestines. The group may also contain patients who suffer lesions to the bile ducts during simple cholecystectomy.
Endoscopic bile duct treatment without simultaneous cholecystectomy
This group consists mainly of patients who only have stones removed
from the bile ducts. Occasionally, a simple cholecystectomy is performed
during a later admission.
Open bile duct surgery without simultaneous cholecystectomy
This group consists mainly of patients who only have stones removed
from the bile ducts and who have previously had their gallbladder removed.
Biliodigestive anastomosis without simultaneous cholecystectomy
This group consists of patients whose bile ducts are altered to such an extent that the surgeon deemed it necessary to perform an anastomosis of
the bile duct and intestines. The majority of these patients have a biliary
tract diagnosis.
20
Other treatment
These courses of treatment represent rare procedures or wrong codes, as
a result of which the patient cannot be categorised in any of the groups
listed above.
Diagnostic ERCP
These courses of treatment represent patients whose bile duct is examined
but not treated immediately or subsequently. These are exploratory procedures in cases where disease of the liver, pancreas or biliary tracts is suspected. However, as no therapeutic operation is performed, they seldom
represent patients with gallstones. The group is included to show how
widespread the use of this technology is, even though it is not without risk.
(Please refer to 7.3.2).
Each course of treatment can be divided according to whether the index
admission is:
❖
the only admission to hospital during the course of treatment,
❖
preceded or followed by an admission for a diagnostic procedure (ERCP)
❖
followed by an admission for a cholecystectomy (only for some courses of treatment)
❖
followed by one or more admissions for endoscopic or open surgery on the bile
duct within a year.
The latter category is assumed to include patients whose course of treatment is complicated, either because of complications to the biliary tract
disease (e.g. stones in the bile ducts) or because of procedure-related complications during the index treatment.
All courses of treatment are mutually exclusive and exhaustive – in
other words, each course of treatment can be placed in one and only one
category.
To assess the total number of hospital admissions accounted for by
gallstone diseases, all admissions for a period of three months before and
one year after the index admission (regardless of the nature of the treatment) were identified in the National Hospital Discharge Register.
Of the 90,582 courses of treatment, 12,262 only involved diagnostic
ERCP without treatment of the biliary tracts. Table 1 breaks down the remaining 78,320 courses of treatment.
In-depth details of how the data from the National Hospital Discharge
Register was processed can be found in enclosure 2.
21
TABLE 1
Breakdown of 78,320 courses of treatment from 1978-95
The treatment during
the index admission
Admissions for biliary tract treatment after the index admission
None
Diagnostic ERCPa
Cholecystectomy
n
n
n
52,132
1,535
469
with endoscopic treatment
430
43
49
0.7
(522)
with open bile duct surgery
8,810
329
280
12.0
(9,419)
with biliodigestive anastomosis
1,414
104
25
2.0
(1,543)
Bile duct
treatment
n
Cholecystectomy
Only procedure
Total
%
(N)
83.8
Bile duct treatment
without cholecystectomy
69.1 (54,136)
12.7
Endoscopic
5,509
941
394
9.7
open surgery
969
71
46
1.4
(1,086)
1,140
160
18
1.7
(1,318)
with biliodigestive anastomosis
764
Other procedures
(7,608)
3.4
Exploration of gallbladder
1,244
21
22
1.6
other
1,155
95
67
84
1.8
Total
72,803
3,278
852
1,387
(1,287)
(1,401)
(78,320)
a: ERCP either before or after the index admission.
2.1.2 The validity of the National Hospital Discharge Register
As far as biliary tract treatments are concerned, the National Hospital
Discharge Register has provided national data throughout the relevant period except 1978 and 1979 when St. Joseph’s Hospital in Copenhagen
was not included. Thus, there is a minor level of underreporting (<2%) in
the first two years.
To validate the data in the National Hospital Discharge Register (enclosure 2), a random sample was extracted including the years 1979, 1985
and 1993 of approx. 10% of the courses of treatment and approx. 2% of
all patients with a biliary tract diagnosis who were admitted to surgical
departments, but who were not treated according to the register. All
courses of treatment involving more than one admission to hospital for
biliary tract procedures were also extracted. In total, 3,570 commentaries
were requisitioned from hospitals around the country. As we go to press,
71% of the commentaries have been received and reviewed to make a provisional assessment. The most significant results are:
❖
22
96% of the courses of treatment were classified correctly. In the remaining 4% of
cases, patients had a different form of biliary tract treatment than the one regi-
stered in the National Hospital Discharge Register. No cases were identified in
which the patient’s biliary tracts were not treated.
❖
99% of admissions recorded in the National Hospital Discharge Register with simple cholecystectomy as index treatment (n=682) were classified correctly. The final
1% consists of patients who had other operations performed on the bile ducts as
well as cholecystectomy. No cases were identified of patients who did not have a
cholecystectomy.
❖
All the entries in the National Hospital Discharge Register recorded as cholecystectomy combined with one or another form of bile duct treatment (n=122) were
found to be classified correctly.
❖
95% of the courses of treatment involving endoscopic bile duct treatment but not
cholecystectomy (n=102) were classified correctly. In the remaining 5% of cases,
diagnostic ERCP was performed but not endoscopic bile duct treatment (1%), or
tubulation of the bile duct without sphincterotomy (4%).
❖
84% of the courses of treatment classified in the National Hospital Discharge Register as exclusively diagnostic ERCP were classified correctly, with a clear trend
towards poorer validity over the years. In 1979, 96% of the classifications were correct, but only 80% in 1993. Among those wrongly classified, 36% of the commentaries contain no information about diagnostics or treatment of the biliary tracts,
while the rest had endoscopic treatment (sphincterotomy or tubulation of the bile
ducts). None of them had a cholecystectomy or an open operation on the bile
ducts.
❖
91% of hospital admissions with a gallstone diagnosis but no treatment code
were classified correctly. The level of accuracy diminishes over the years, since 94%
were correct for the first two years, but only 82% correct in 1993. Among those
wrongly classified, 25% had diagnostic ERCP, while the rest had endoscopic treatment (sphincterotomy or tubulation) of the biliary tracts. None had the gallbladder removed or open surgery of the biliary tracts.
It can be concluded that the data in the National Hospital Discharge Register forms a particularly suitable basis for the assessment of how often
cholecystectomy and open bile duct surgery are performed.
As regard therapeutic ERCP the underreporting is big. The scale of underreporting can be calculated on the basis of the proportion of wrongly
classified therapeutic ERCP in the groups where they were observed (endoscopic procedure without cholecystectomy, diagnostic ERCP and stays
in hospital without any treatment of the biliary tract) and comparing this
23
proportion with the response rate and total number of admissions registered in the National Hospital Discharge Register in the relevant categories. This suggests an underreporting of therapeutic ERCP levels
amounting to 75% in 1979, 42% in 1985 and 23% in 1993. The estimates for 1979 and 1985 were based on very small numbers (since few
sphincterotomies were performed) and, as such, are subject to a certain
degree of uncertainty. The relatively lower level of underreporting in 1993
than in 1985 and 1979 has to be compared with the much higher number
of sphincterotomies in 1993 (n=1091) than in 1985 (n=233) and 1979
(n=63). As a result of this, the level of underreporting has a greater impact
in 1993 than in the other two years in question.
The validation survey is badly suited to assessing the extent to which diagnostic ERCP is underreported or overreported, since the majority of diagnostic ERCP is exploratory and only remains diagnostic if the patient has
nothing wrong with his or her biliary tract. A survey of this correlation
would require an extract of admissions classified as neither biliary tract
treatment nor a biliary tract diagnosis. In other words, to find admissions
for ERCP not registered in the National Discharge Register would require
an extract of several thousands additional commentaries. However, it can
be surmised that the pattern of reporting will be the same as for therapeutic ERCP since both procedures are registered by the same staff.
Once the remaining commentaries have been received, a total analysis
of the validation will be sent to the Weekly Journal of the Danish Medical
Association for potential publication.
2.2
L ITERATURE
To identify what evidence exists for the best treatment of the different
types of gallstone disorders, an in-depth study was conducted of the scientific literature in the field. So much literature now exists that it was necessary to lay down principles for the method in which they were studied
in order to avoid misinterpretations. Thus, it is important that all articles
regarding a given subject are identified and assessed according to fixed criteria. This work compares with a scientific survey. Criteria for selection
and assessment of articles and research results are listed in appendix 3.
The following themes have been studied systematically:
24
❖
Natural history of gallstone disorders
❖
Symptoms of stones in the gallbladder
❖
Cholecystectomy rates since 1978
❖
Comparisons of different technologies for elective treatment of stones in the gallbladder
❖
Randomised surveys comparing different technologies for the treatment of stones
in the bile ducts.
2.3
D ANISH POPULATION STUDIES
At the Copenhagen County Centre of Preventative Medicine, Glostrup
University Hospital, the occurrence of gallstones in the Danish population
has been studied since 1982. These epidemiological data include random
samples from the population in the western area of Copenhagen County.
A total of 5,936 people have undergone ultrasound scanning for gallstones. Many of them have been examined three times over a ten-year period. The cohorts have been linked to the National Hospital Discharge
Register and the Civil Registration System and constitute a major source
of data for a more in-depth study of the natural history of gallstones and
their importance in terms of general morbidity and mortality. A certain
amount of unpublished data from these studies has been used in this report and marked with a specific reference371.
2.4
S TAFF AND STAFF TIME IN THE TREATMENT OF GALLSTONE PATIENTS IN
D ENMARK
In 1997, a questionnaire was sent out to all the surgical departments in the
country and to specially selected medical gastroenterological departments
regarding the number of staff and the amount of staff time spent on biliary tract operations and on diagnostic and therapeutic ERCP. Recipients
were not sent reminder letters. The response rates were 67% for the surgical departments and 100% for the medical gastroenterological departments. The results of this survey are included in enclosure 5.
2.5
T HE N ATIONAL R EGISTER FOR L APAROSCOPIC C HOLECYSTECTOMY
The National Register for Laparoscopic Cholecystectomy is a clinical
database kept by Dansk Kirurgisk Selskab (Danish Society of Surgeons).
It registers all the laparoscopic cholecystectomies performed in Denmark
since 1991. The database contains information about patients who have
had a laparoscopic cholecystectomy. At an early stage of the work on this
report, we contacted the National Register for Laparoscopic Cholecystectomy to find out whether we could work closely together. The National
25
Register covers a selected section of the patient population and does not
contain data from before 1991. Publications from the Register are referred to in a number of situations in this report.
2.6
A NALYSES
The analyses of data from the National Hospital Discharge Register cover
the period 1978-95. In several tables and figures, this 18-year period has
been divided up into four sub-sections: i.e. 1978-83, 1984-87, 1988-91
and 1992-95. This was done in order to provide sufficient material for the
analyses and to take into account technological progress. Period one represents a stable period during which gallstone treatment did not change
significantly, while the two middle periods cover the spread of ultrasonic
drainage in the treatment of acute cholecystitis and ERCP. The final period represents the period when laparoscopic cholecystectomy was introduced in the majority of departments in Denmark.
Calculation of rates in relation to period, gender and age
The population of Denmark rose from 4,937,579 (1 January 1978) to
5,251,027 (1 January 1996). The proportion of elderly citizens also rose
during this period. In order to compare developments in the various treatments, the number of patients has been calculated per 100,000 and standardised in terms of age in relation to the 1995 population. Gender and
age-specific operation rates have been calculated for each of the four periods. Changes in operation rates for age groups and periods have been
analysed more closely with the help of a statistical model described in enclosure 4. The model takes into account that the development in operation rates according to age is different for men and women and can also
vary between the four time periods.
Regional variations
Sub-division into the four periods of time was used when estimating regional variations. Population-based operation rates were calculated for
geographic areas roughly corresponding to a given hospital for each period. These hospital admission area was defined by studying which hospital carried out the majority of the operations in question in any given
municipality. Grouping municipalities mainly served by the same hospital
constitutes a single hospital admission area. If a hospital closed during any
of the periods, it was grouped together with the hospital that took over
the majority of patients. The municipalities of Copenhagen and Frederiks-
26
berg were considered a single admission area. A statistical model (Poisson)
was used to estimate the age-standardised rates. Since the admission areas
vary in size and the statistical uncertainty varies accordingly, a so-called
‘random effect model’ was used to align operation rates based on small
numbers with the national average. The relative differences in the frequencies of operations described in the report are thus cautious estimates
of the regional variation. This has proven to be an acceptable method of
approximation109. The statistical method is described in more depth in
enclosure 4.
Mortality and morbidity
Logistic regression analysis was used to calculate mortality and morbidity. Tests were run to identify significant interactions. The results are given
as odds ratio (OR) with 95% confidence limits. OR stipulates the relative
difference in morbidity and mortality between the groups being compared.
27
3. Occurrence, natural history
and prevention
3.1
G ALLSTONE DISORDERS IN THE D ANISH POPULATION
Gallstones are common in the Danish population. By comparing two
screening surveys in Denmark (1982-84365, 375 and 1991371, respectively) a
fall of 11% was detected in gallstone disorders (both people with gallstones and people who had a cholecystectomy) (table 2). The fall is insignificant but corresponds to the fall observed in Denmark since World
War II770, 771. The proportion of people with gallstone disorders who undergo a cholecystectomy also fell insignificantly during the period (table 2),
corresponding to the falling cholecystectomy rate in the country until
1991 (see section 5.1).
TABLE 2
Age-standardised occurrence of gallstone disorders (both people with gallstones and those
who had a cholecystectomy) and the proportion who have been cholecystectomised in a
random cross-section of the Danish population (N=5,936) resident in the Western part of
Copenhagen County.
Prevalence of gallstone disorders a
1982-84
%
Men
1991
%
OR (95% c.l.)c
1991 >< 1982-4
The proportion who have a cholecystectomy b
1982-84
%
1991
%
OR (95% c.l.)c
1991 >< 1982-4
7.2
6.5
0.91 (0.66-1.25)
23.3
22.2
1.07 (0.53-2.17)
Women
13.7
12.0
0.88 (0.69-1.13)
38.7
31.9
0.66 (0.41-1.06)
Total
10.4
9.2
0.89 (0.73-1.08)
33.2
28.4
0.77 (0.52-1.14)
a: The presence of gallstones was detected by ultrasound scan 365, 371, 375.
b: Among those with gallstone disorders.
c: Standardised for age (and gender).
On the basis of the above-mentioned cohort studies from Copenhagen
County Centre of Preventative Medicine, Glostrup University Hospital371, 373
(see section 3.2) and information from Statistics Denmark regarding the age
and gender composition of the Danish population, it was estimated that approx. 450,000 people suffered from gallstone disorders in 1991, and that of
those approx. one third had a cholecystectomy. The rest (approx. 300,000)
had stones in the gallbladder. Since gallstones are usually asymptomatic,
practically none of these people will be aware of their gallstones368.
28
3.2
T HE NATURAL HISTORY OF PEOPLE WITH UNTREATED GALLSTONES
As stated, some people with gallstones progress through all the phases
from an asymptomatic condition, to symptoms, to complications. Not
many publications exist about the natural history of gallstones, since most
people have their stones diagnosed and treated. Thus, the available literature consists mainly of selected patient cohorts (table 3). Even though
there may be an identifiable group with asymptomatic stones within these
cohorts, there has probably been a reason why the patients had their gallbladders examined, so it is open to question how asymptomatic they really were. Only three works represent definitive asymptomatic cases, identified by screening54, 220, 289 and they reveal complication rates of 0.2-0.8%
per annum. The other studies that describe patients as asymptomatic
show complications rates of 0.3-1.2% per annum. Patients with symptomatic stones have complications rates of 0.7-2.0% per annum. The participants in a Danish cohort survey in 1982-84 with a five-year follow-up
period354, 371 were divided into those who knew they had gallstones (symptomatic and previous complications), those who did not know they had
gallstones (asymptomatic) and those who generated stones during the
five-year period. The annual complications rates were 4%, 0.4% and 0%,
respectively.
The cohorts identified from the literature include a total of some 3,000
gallstone patients. A combination of the relatively small number and the insufficient information about the patients from base-line, makes it difficult to
identify those particularly susceptible to complications. However, women
tend to develop complications more often than men. Gallbladder cancer was
revealed in a total of 10 patients in these cohorts – corresponding to a 0.3%
risk over a period of up to 30 years, which is negligible.
Thus, the literature shows that the natural history of stones in the gallbladder is relatively uneventful. A decision analysis630 also confirms that
there is no great benefit – as far as survival is concerned – of operating on
a patient with gallstones after the first pains.
29
TABLE 3
Follow-up of patient cohorts with stones in the gallbladder.
Author
Country
Year a
N
Follow-up b
Complications
Asymptomatic gallstones
Comfort152
USA
1925-34
112
15 years
4.5%
(0.3%/year)
Gracie c, 289
USA
1956-69
123
11 years
2.4%
(0.2%/year)
McSherry508
USA
-
135
5 years
3.0 %
(0.6%/year)
Wolpers854
Germany
1950-80
145
13.5 years
16.7%
(1.2%/year)
Friedmand d, 251
USA
1967-73
123
20 years
Cucchiaro164
USA
1982-83
125
5 years
1.6%
(0.3%/year)
delFaveroe, 220
Italy
1984-85
47
5 years
4.2%
(0.8%/year)
Attilic, 54
Italy
1980
118
10 years
3.0%
(0.3%/year)
1936-50
296
13 years
about 25% (1.9%/year)
-
305
2 years
1.3%
(0.7%/year)
USA
1930-45
116
221⁄2 years
Sweden
1951-52
781
11 years
18%
(1.6%/year)
10%
(1.7%/year)
6.5%
(0.7%/year)
(1%/year)
Both asymptomatic and symptomatic gallstones
Lund469
Denmark
Thistle776
USA
Symptomatic gallstones
Ralston629
Wenckert
831
McSherry508
USA
-
556
6 years
Friedmand d, 251
USA
1967-73
298
25 years
Attilic, 54
Italy
1980
33
10 years
(2%/year)
(1%/year)
A further seven surveys were identified but the information was either insufficient 93, 564, 608, 791, 853 or written in a language not covered by
this report 285, 639.
a: The period of time during which the cohort was formed.
b: Attempts have been made to estimate a median follow-up time.
c: Healthy people screened for gallstones.
d: This study is the only one that used a correct method of analysis (life-table analyses), in which account is taken of the fact that not all
patients are observed for the same length of time. The consequence of not using the correct method is that the frequency of complications is underestimated.
e: Diabetes patients screened for gallstones.
3.3
P REVENTION OF GALLSTONES
3.3.1 Primary prevention
Primary prevention removes or modifies the risk factors associated with
gallstone formation in such a way that stones do not form. The modifiable risk factors are obesity42, 62, 369, smoking369, 375, lack of exercise371 plus
a low-fibre diet, rich in saturated fats611, 784. These are the same lifestyle
factors involved in the prevention of cardiovascular diseases, a topical priority in Denmark. No studies have attempted to document the extent to
which changes in these lifestyle factors lead to a reduction in the incidence
of gallstones.
Primary prevention has been applied to overweight people who planned a comprehensive weight loss. They run a particularly high risk of de-
30
veloping gallstones, since some of the excess cholesterol from the weight
loss is secreted through the bile331. In theory, adjuvant bile salt therapy
ought to reduce the risk of gallstone formation. Two randomised surveys
of this subject were found. In one of them,709 the patients participated
(N=1,004) in a low calorie weight reduction programme, while the patients (N=233) in the other study760 underwent operations on the stomach
(gastric bypass) to reduce the intake of food. Both studies show that a
daily dosage of 600 mg ursodeoxycholic acid during the weight reduction
period reduced gallstone lithiasis to 2% compared with 28-32% in the
placebo group. However, there are no follow-up studies to cast light upon
the clinical significance of this difference in gallstone formation. Spontaneous dissolution of gallstones after weight loss was identified in other
studies451. By ensuring a moderate weight loss (<1.5 kg/per week), the risk
of gallstone formation should be reduced827. However, this has not been
tested in a randomised design.
Patients subjected to long periods of parenteral alimentation run a high
risk of forming gallstones because of lack of gallbladder contraction487. A
single randomised study revealed that a daily dosage of cholecystokinin (a
hormone that causes contraction of the gallbladder) prevents the preliminary stages of gallstone formation during parenteral alimentation715.
3.3.2 Secondary prevention
Secondary prevention identifies and removes the gallstones before symptoms or complications develop. In the 60s, several authorities279, 469 advocated prophylactic cholecystectomy - in other words cholecystectomy for
people with gallstones but without characteristic symptoms. The argument was that performing a cholecystectomy while the patient is young
and healthy and has not yet developed complications to the gallstone disorders, will cause lower morbidity and mortality than performing an operation when the person is older, has developed other illnesses and has a
more complicated biliary tract disease. Since a lot of stones remain asymptomatic, this approach would lead to a high proportion of superfluous
cholecystectomies. A single study revealed that greater reluctance to perform cholecystectomy lead to an increased complication rate of 22%, increased morbidity, but unchanged mortality187. The question is whether a
lot of people should undergo surgical procedures to lower the postoperative morbidity in the few. Decision analyses based on the literature reveal
for both traditional open cholecystectomy and laparoscopic cholecystectomy222, 252, 631 that prophylactic cholecystectomy leads to a slight increase
31
in mortality. Because of these results, prophylactic cholecystectomy is not
recommended in the international recommendations44, 45, 46.
No articles were found that describe systematic attempts at secondary
prevention using medical dissolution of gallstones, even though medical
treatment probably has the highest success rate at the point in time when
the stones have just formed and have not yet calcified. A secondary prophylaxis would require screening of sections of the population for gallstones, which would be very expensive331. Selective screening of high-risk
groups may be justifiable; e.g. screening of pregnant women. Pregnancy
seems to be the largest single risk factor in gallstone formation, and in
some studies the gender difference in the incidence of gallstones is explained exclusively by pregnancy366, 375, which means that up to half of
gallstones in women can be ascribed to pregnancy. One single large
study792 found that 2% formed stones during pregnancy, but that some of
these stones may disappear again after the birth802. No studies have assessed the possibility of screening and subsequent ESWL treatment right
after the birth and bile salts once breast feeding has stopped. The method
might prove cost-efficient if it halves the number of women operated on
at a later date.
32
4. Treatment of patients with
benign biliary tract disorders
in Denmark 1978-95
This chapter looks at all 78,320 courses of treatment for biliary tract disorders in Denmark in the period 1978-95 (figure 10) and gives an overall
picture of the volume of treatment. Diagnostic ERCP (N=12,262) is discussed separately. The subsequent chapters (5-8) describe the various
main areas within biliary tract treatment.
Treatment of biliary tract disorders
The 78,320 courses of treatment correspond to 4,351 annual treatments in
Denmark, and approx. 85% of these included a cholecystectomy. The number did not remain constant throughout the period. From a relatively high
rate for women (figure 10) in 1978 there was a fall of 30% (2.3% per annum) until 1991, after which the rate rose by 25% (6.3% per annum). The
corresponding figure for men (figure 10) showed a fall of 21% (1.6% per
annum) from 1978 to 1991 followed by a rise of 22% (5.5% per annum).
FIGURE 10
All operations with biliary tract diagnosis
Rate per 100,000
150
125
100
75
50
25
0
Year 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95
Women
Men
33
Treatment for biliary tract disorders is rare in females under age 10-15
years. The number of treatments rises until 30, interrupted by a minor fall
until 40, only to rise again after 40 (figure 11). The age distribution
changed during the period studied. In the first three sub-periods (until
1991), more or less the same number of young women were treated,
whereas the number of women over 40 undergoing treatment declined
over the years. During the final sub-period (1992-95), there was a significant rise among all age groups except 70+, in which the number of treatments remained the same as the previous periods. In men, gallstone treatment starts a bit later than in women (age 20-25 years) but there is no
break in the age curve (figure 12), only an exponential rise with age. As
far as the tendency in the different sub-periods is concerned, the pattern is
the same as for women. While the number of gallstone treatment shows a
tendency to recede in older women, it continues to rise in men.
FIGURE 11
All operations with biliary tract diagnosis - women
Rate per 100,000
320
280
240
200
160
120
80
40
0
Age 0
10
1978-1983
34
20
30
1984-1987
40
50
1988-1991
60
70
1992-1995
80
FIGURE 12
All operations with biliary tract diagnosis - men
Rate per 100,000
320
280
240
200
160
120
80
40
0
Age 0
10
1978-1983
20
30
1984-1987
40
50
1988-1991
60
70
80
1992-1995
Figures 13-20 reveal the regional differences for all courses of treatment.
The dark red areas denote high operation rates, while dark green areas
denote low operation rates. A total of 10% of the areas are significantly
above, and 12% significantly below, the average for women, while the
corresponding figures for men are 6% and 6%. The greatest differences
appear to be during the first and last sub-periods. The relative difference
between the area with the highest and the lowest operation rate in the
four sub-periods was 1.9, 1.5, 1.7 and 2.2 for women, which means that
twice as many women were treated in one area as in another after account
has been taken of random variation and differences in age distribution
between the areas. The corresponding figures for men were 2.0, 1.8, 2.0
and 2.2.
35
FIGURE 13
All operations on biliary tracts – women, 1978-1983
SMR
< 0.7
1 - 1.1
0.7 - 0.8
1.1 - 1.2
min = 0.72 max = 1.35
36
0.8 - 0.9
1.2 - 1.3
0.9 - 1.0
> 1.3
FIGURE 14
All operations on biliary tracts – women, 1984-1987
SMR
< 0.7
1 - 1.1
0.7 - 0.8
1.1 - 1.2
0.8 - 0.9
1.2 - 1.3
0.9 - 1.0
> 1.3
min = 0.83 max = 1.22
37
FIGURE 15
All operations on biliary tracts – women, 1988-1991
SMR
< 0.7
1 - 1.1
0.7 - 0.8
1.1 - 1.2
min = 0.79 max = 1.33
38
0.8 - 0.9
1.2 - 1.3
0.9 - 1.0
> 1.3
FIGURE 16
All operations on biliary tracts – women, 1992-1995
SMR
< 0.7
1 - 1.1
0.7 - 0.8
1.1 - 1.2
0.8 - 0.9
1.2 - 1.3
0.9 - 1.0
> 1.3
min = 0.65 max = 1.42
39
FIGURE 17
All operation on biliary tracts – men, 1978-1983
SMR
< 0.7
1 - 1.1
0.7 - 0.8
1.1 - 1.2
min = 0.70 max = 1.38
40
0.8 - 0.9
1.2 - 1.3
0.9 - 1.0
> 1.3
FIGURE 18
All operation on biliary tracts – men, 1984-1987
SMR
< 0.7
1 - 1.1
0.7 - 0.8
1.1 - 1.2
0.8 - 0.9
1.2 - 1.3
0.9 - 1.0
> 1.3
min = 0.73 max = 1.29
41
FIGURE 19
All operation on biliary tracts – men, 1988-1991
SMR
< 0.7
1 - 1.1
0.7 - 0.8
1.1 - 1.2
min = 0.72 max = 1.42
42
0.8 - 0.9
1.2 - 1.3
0.9 - 1.0
> 1.3
FIGURE 20
All operation on biliary tracts – men, 1992-1995
SMR
< 0.7
1 - 1.1
0.7 - 0.8
1.1 - 1.2
0.8 - 0.9
1.2 - 1.3
0.9 - 1.0
> 1.3
min = 0.65 max = 1.43
43
Mortality
The 30-day mortality rates exhibit a minor fall in the period 1978-95 if all
operations are considered (figure 21). However, the curves do reveal some
variation.
The rates are standardised for age and gender. To assess the changes in
mortality in greater depth and take into account differences in other forms
of ill-health (co-morbidity), the four sub-periods were compared by means
of logistic regression analysis (table 4). These analyses showed a tendency
for mortality to rise among acute admissions over the years, while in a
single period (1988-91) there was a significant fall in mortality among the
elective admissions. No international literature was found which analyses
mortality rates associated with all biliary tract procedures.
TABLE 4
The 30-day mortality a after operation on biliary tracts in relation to diagnosis and period of
time in Denmark, 1978-95. Only courses involving biliary tract diagnoses have been included
and the analyses (multiple logistic regression analyses) take into account age, gender and
co-morbidity.
All operations on biliary tracts
Elective admission
Acute admission
Total
OR (95% c.l.)
OR (95% c.l.)
OR (95% c.l.)
1978-1983
1.00
1.00
1.00
1984-1987
0.92 (0.69-1.22)
1.22 (1.03-1.44)
1.11 (0.96-1.28)
1988-1991
0.68 (0.47-0.97)
1.25 (1.05-1.49)
1.08 (0.93-1.26)
1992-1995
0.75 (0.52-1.07)
1.18 (0.98-1.42)
1.04 (0.88-1.22)
Period
a: Mortality is measured from the date of admission, as the actual date of operation is not stipulated in the National Hospital Discharge
Register
Diagnostic ERCP
The 12,262 admissions correspond to 681 patients per annum undergoing
diagnostic ERCP not followed by treatment of the biliary tracts. There is
a significant change during the period of 300% for women and 250% for
men (figure 22). The rise is particularly pronounced after the introduction
of laparoscopic cholecystectomy.
The findings correspond to international literature232, 698. Since diagnostic
ERCP does not usually lead to a gallstone diagnosis, the rise must be due
to the fact that this technology is being used increasingly often to examine patients suspected of having biliary tract disorders.
44
FIGURE 21
Mortality rates standardised for gender and age
Number per 1,000
50
45
40
35
30
25
20
15
10
5
0
Year 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95
Acute
Total
Elective
FIGURE 22
ERCP
Rate per 100,000
30
25
20
15
10
5
0
Year 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95
Women
Men
45
Conclusion
It can be concluded that the total number of treatments for biliary tract
disorders in Denmark fell during the 80s but rose again after the introduction of laparoscopic cholecystectomy. Due to the underreporting of endoscopic bile duct surgery, it can only be presumed that the rise after 1991
has been even more pronounced than the curves suggest. The regional
variations, which reflect differences in ill-health and patient behaviour as
well as lack of consensus about examination and treatment indication,
show a moderate variation pattern. The overall mortality showed no significant difference during the time periods with a tendency towards decreasing mortality among patients admitted electively and increasing mortality in patients admitted acutely. The use of diagnostic ERCP rose
steadily during the whole period, more rapidly after the introduction of laparoscopic cholecystectomy.
46
5. Treatment of patients with
non-complicated gallbladder
stones
5.1
D EVELOPMENTS IN D ENMARK , 1978-95
5.1.1 The frequency of simple cholecystectomy
The treatment rate for simple cholecystectomy (including patients with
acute cholecystitis) has changed noticeably during the period 1978-95
(figure 23). A relatively constant operation rate for women in the early
years was followed by a fall of 21% (3% per annum) from 1984 to 1991
and a rise of 27% (9% per annum) to 1994. For men, a corresponding fall
of 26% (3.7% per annum) was recorded from 1984 to 1991, followed by
a rise of 18% (4.5% per annum) until 1995.
FIGURE 23
Simple cholecystectomy - with biliary tract diagnosis
Rate per 100,000
110
100
90
80
70
60
50
40
30
20
10
0
Year 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95
Women
Men
The treatment rates for simple elective cholecystectomy (figure 24) reveal
more pronounced variations than the rates for all simple cholecystec-
47
tomies (figure 23). The fall for women from 1984 to 1991 was 24%
(3.4% per annum) and the subsequent rise until 1994 was 44% (14.7%
per annum). For men, a corresponding fall of 35% (5% per annum) from
1984 to 1991 was followed by a rise of 21% (5.3% per annum) until
1995.
FIGURE 24
Simple cholecystectomy - without acute cholecystitis - with biliary tract diagnosis
Rate per 100,000
90
80
70
60
50
40
30
20
10
0
Year 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95
Women
Men
The cholecystectomy rate for women (including operation for acute cholecystitis) in different age groups (figure 25) fell during the first three subperiods for the over-40s and rose during the final sub-period for the 4070s. The most prominent feature in the younger groups was a steep rise
after the introduction of laparoscopic cholecystectomy – a rise of almost
50%. All the curves break, with the cholecystectomy rate rising until 30,
falling slightly until 40 and then rising again. This break is particularly
pronounced in the final sub-period. The break in the curve is equally pronounced all over the country. There is no break in the age curve for men
(figure 26). It continues to rise with age. The variation over the four subperiods was the same as for women.
48
FIGURE 25
Simple cholecystectomy - women, with biliary tract diagnosis
Rate per 100,000
220
200
180
160
140
120
100
80
60
40
20
0
Age 0
10
1978-1983
20
30
40
1984-1987
50
60
70
80
1992-1995
1988-1991
FIGURE 26
Simple cholecystectomy - men, with biliary tract diagnosis
Rate per 100,000
220
200
180
160
140
120
100
80
60
40
20
0
Age 0
10
1978-1983
20
30
1984-1987
40
50
1988-1991
60
70
80
1992-1995
Discussion
The fall in the cholecystectomy rate from 1983-91 corresponds with most
of the observations from Europe and USA128, 186, 187, 417, 426, 510, 540, 605, 648 apart
49
from one single study745 that revealed no change. The fall in the cholecystectomy rate until the introduction of laparoscopic cholecystectomy was
probably due to the increasing use of new technologies instead of traditional open cholecystectomy, e.g. ESWL and bile salts, ultrasound
drainage of the gallbladder in the event of acute cholecystitis and percutaneous dissolution of gallstones. There was probably a minor fall in the
incidence of gallstones as well (see section 3.1).
The rise in the cholecystectomy rate after the introduction of laparoscopic cholecystectomy followed the international pattern. A systematic
literature search identified six studies of cholecystectomy rates covering
well-defined regions (even whole countries) that uses standardisation in
relation to the size of the population, age and gender (table 5). Results
from individual hospitals667, 682, 746 were not included since the size of the
patient base can change. To ensure comparability with the other studies,
the genders have been mixed and all cholecystectomies (regardless of simultaneous bile duct surgery) included in the Danish figures in the table.
The data reveals that the rise in the Danish cholecystectomy rate is greater
than in Scotland and than in one of the American studies, but also far
smaller than in two other areas in the USA. Other studies149, 426 show in accordance with this study that the rise in the cholecystectomy rate was particularly pronounced among young women.
TABLE 5
Changes in the cholecystectomy rate (per 1,000 people) after the introduction of laparoscopic
cholecystectomy.
Author
1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 Rise
Legoretta438
Cobb146
3.87
Steiner745
1.65
213
Escarce
Cohen
1.65
3.4
1.68
3.5
1.37
1.35
1.59a 2.01
1.68
1.69
1.84a 2.16
3.5
149
3.3
a
3.6
a
Country
2.15
59.3% USA
7.22
86.5% USAb, c
2.17
28.4% USA
4.1
4.4
4.2
33.3% USA; >64 år c
18.8% USA
2.75
2.82
3.01
3.25
3.04
Lam426
0.90
0.91
0.89
0.88
0.86
0.85a 0.80
0.93
1.03
This study d
0.60
0.58
0.59
0.57
0.54
0.53
0.53a 0.58
0.66
19.8% The whole of Scotland
0.67
26.4% The whole of Denmark
All studies covered an average of more than 900 cholecystectomies per annum. The major difference in the cholecystectomy rates
between USA on the one hand and Scotland and Denmark on the other is due to a higher prevalence of gallstones in the USA (section 1.1).
a: States the year in which laparoscopic cholecystectomy was introduced.
b: The exact periods of time are 01.07.84-30.06.85 and 01.07.91-30.06.92. Laparoscopic cholecystectomy was introduced between the
two periods
c: Only patients insured by Medi Care. Thus, the base population is variable and theoretically there could have been a larger increase in
patient numbers after the introduction of laparoscopic cholecystectomy, which would lead to over-estimating.
d: Includes all cholecystectomies – including patients who also received treatment of the bile duc.
50
A series of American and Australian reports showed the rise in the number of cholecystectomies without taking into account any changes in the
age and gender composition of the total population3, 206, 232, 554, 577, 658, 660.
These rises vary from 28% to 39.6%, but since the population in the areas in question must be expected to have grown older, the estimates will
be slightly too high. In addition to the present study, and the Scottish
study426, two other national studies have been conducted into changes in
cholecystectomy rates. The cholecystectomy rates have, however, not been
standardised, so the statistical rises of 24% in Australia489 and 17% in
Canada489 are presumably slightly too high.
The cause of the rise in the cholecystectomy rate after the introduction
of laparoscopic cholecystectomy is not known, but is presumed to be due
to a lower threshold for treatment. One article reported that an informal
survey of 19 gastroenterologists revealed that 17 had modified the indications for cholecystectomy578.
The lower of the high points in the cholecystectomy rate around 30 years
for women has not been described in the literature before. It may be due to
gallstones formed during pregnancy. Ultrasound scanning is frequent during
pregnancies, and as a result, asymptomatic gallstones may be discovered
more frequently in pregnant women because it is difficult to avoid the gallbladder when conducting an ultrasound examination of the abdomen.
Conclusion
The cholecystectomy rate in Denmark and abroad fell throughout the 80s.
After the introduction of laparoscopic cholecystectomy, the cholecystectomy rate rose noticeably. The rise in Denmark was greater than in Scotland, Canada and Australia, but less than in certain areas of USA.
5.1.2 Regional variations in Denmark
Regional variations for simple cholecystectomy (including acute cholecystitis)
in Denmark (figure 27-34) were moderate. Among women 10% of the areas
were significantly below and 15% significant above the average. The corresponding figures for men were 3% and 6%. There was a distinct tendency
for regional variations to be greatest in the first and last sub-periods. The
differences between the areas with the lowest and highest cholecystectomy
rates for women during the periods 1978-83, 1984-87, 1988-91 and 199295 were 2.2; 1.6; 1.8 and 2.5, respectively, while the corresponding numbers
for men were 2.1; 1.4; 1.7 and 2.1. Thus, taking into account random variation and age differences, more than twice as many people had a cholecystectomy in one area of Denmark during the final sub-period as in another.
51
FIGURE 27
Simple cholecystectomy – women 1978-1983
SMR
< 0.7
1 - 1.1
0.7 - 0.8
1.1 - 1.2
min = 0.66 max = 1.47
52
0.8 - 0.9
1.2 - 1.3
0.9 - 1.0
> 1.3
FIGURE 28
Simple cholecystectomy – women 1984-1987
SMR
< 0.7
1 - 1.1
0.7 - 0.8
1.1 - 1.2
0.8 - 0.9
1.2 - 1.3
0.9 - 1.0
> 1.3
min = 0.80 max = 1.25
53
FIGURE 29
Simple cholecystectomy – women 1988-1991
SMR
< 0.7
1 - 1.1
0.7 - 0.8
1.1 - 1.2
min = 0.80 max = 1.47
54
0.8 - 0.9
1.2 - 1.3
0.9 - 1.0
> 1.3
FIGURE 30
Simple cholecystectomy – women 1992-1995
SMR
< 0.7
1 - 1.1
0.7 - 0.8
1.1 - 1.2
0.8 - 0.9
1.2 - 1.3
0.9 - 1.0
> 1.3
min = 0.63 max = 1.59
55
FIGURE 31
Simple cholecystectomy – men 1978-1983
SMR
< 0.7
1 - 1.1
0.7 - 0.8
1.1 - 1.2
min = 0.71 max = 1.47
56
0.8 - 0.9
1.2 - 1.3
0.9 - 1.0
> 1.3
FIGURE 32
Simple cholecystectomy – men 1984-1987
SMR
< 0.7
1 - 1.1
0.7 - 0.8
1.1 - 1.2
0.8 - 0.9
1.2 - 1.3
0.9 - 1.0
> 1.3
min = 0.83 max = 1.16
57
FIGURE 33
Simple cholecystectomy – men 1988-1991
SMR
< 0.7
1 - 1.1
0.7 - 0.8
1.1 - 1.2
min = 0.80 max = 1.34
58
0.8 - 0.9
1.2 - 1.3
0.9 - 1.0
> 1.3
FIGURE 34
Simple cholecystectomy – men 1992-1995
SMR
< 0.7
1 - 1.1
0.7 - 0.8
1.1 - 1.2
0.8 - 0.9
1.2 - 1.3
0.9 - 1.0
> 1.3
min = 0.68 max = 1.43
59
Diskussion
Regional variations have been described in many countries. Most works
stem from the 60s and 70s239, 449, 507, 834, but a few later publications show
either the same variation393 or slightly greater variations610 than in Denmark. One Nordic report478 revealed regional variations in cholecystectomy rates in the other Nordic countries corresponding to those in Denmark. The variation may simply reflect variations in gallstone incidence in
different regions, which is probably not the case in Denmark367. In Denmark, the differences are probably due to differences in patient behaviour
or in definitions of indications for diagnostics and treatment.
5.2
W HICH SYMPTOMS ARE DUE TO STONES IN THE GALLBLADDER ?
There is international consensus (see section 3.3.2) that patients should
not be treated for stones in the gallbladder until they develop symptoms.
Since 30-40% of the population suffer gastrointestinal symptoms382 and
up to 20-30% have stones in the gallbladder370, coincidence will often
occur. The challenge for clinicians is to find out which symptoms are
caused by gallstones and which are not45. This area has been the object of
major disagreement over the years, ranging from the extreme view that all
gallstones cause symptoms “as long as you interrogate the patient
thoroughly “496 to the other extreme view that stones do not cause symptoms until complications set in2.
In an attempt to discover which symptoms are due to stones in the gallbladder and, therefore, which symptoms should be included in the indication for cholecystectomy, a thorough study was conducted of articles
concerning:
❖
The description of gallstone symptoms in uncontrolled clinical series
❖
Comparison of symptoms in people with and without gallstones:
- in populations screened for gallstones
- among patients examined for suspected gallstones
❖
Incidence of - and predictors for - continued symptoms after removal of gallstones
Excepting articles describing gallstone symptoms in uncontrolled series,
the study tried to trace all articles (see however appendix 3) that fulfil the
following requirements: a) screening surveys of at least 100 people from
random samples of the population; b) consecutive series of at least 100 patients examined for gallstones during well-defined periods and, finally c)
60
articles about persistent pain after cholecystectomy had to cover consecutive series of at least 50 patients in well-defined time periods.
Description of gallstone symptoms in uncontrolled clinical series
No attempt was made to conduct a systematic literature search of this category, since these studies are unsuitable to identify which pains are specific
to stones in the gallbladder. However, some of the older works contain
very detailed descriptions of symptoms in patients with gallstones, symptoms which it might be beneficial to compare with findings from newer,
controlled series. The traditional gallstone pains are described as very severe - comparable with birth pains249, 295. The pains either start suddenly
or reach a climax during a period of 10-60 minutes, after which they remain present and constant for several hours before fading away slowly.
The pain is in the top of the stomach or the top right-hand side of the abdomen, often radiates towards the back and/or right shoulder/shoulder
blade. Attacks are usually weeks or even years apart. Gallstone patients
experience more constant pains than patients with kidney stones 249. Compared with patients who suffer abdominal pains for other reasons, gallstone patients usually suffer pains at night with a tendency for the majority of the attacks to occur at the same time of day643.
Comparison of symptoms in people with and without gallstones
Seven out of 16 screening studies revealed a significant relationship between gallstone-like pains or pains in the upper abdomen and the incidence of stones in the gallbladder. Twelve of the studies also assessed the
relationship between dyspepsia and gallstones, which was significant in
two of the studies. The studies are summarised in appendix 3 (table 1).
Seven studies were identified in which patients referred to a clinical
department or to an X-ray department were asked about their symptoms
before the actual examination for gallstone was conducted. Most of the
series revealed that patients with gallstones suffer upper abdominal pains
more often than those who do not have gallstones, whereas only one study
out of six identified a relationship between dyspepsia and gallstones. The
studies are summarised in appendix 3 (table 2).
Occurrence of persistent symptoms in patients after cholecystectomy
If a symptom persists after cholecystectomy, the gallstones or the gallbladder may not have been the cause of the symptoms. Conversely, the
fact that symptoms disappear after a cholecystectomy does not necessar-
61
ily mean that the symptoms were caused by the gallstones/gallbladder. A
certain level of placebo effect cannot be discounted. Furthermore, abdominal symptoms are not constant in individual patients, but show great
variation over time382. In 19 clinical series identified, the incidence of persistent symptoms varied from 6% to 41% (average 22%); though only
from 3% to 17% (average 9%), if symptoms had to have the same
strength and regularity as before the operation. The only predictors for
persistent pains are dyspepsia along with pains70, 468, atypical pains along
with typical pains 409, longstanding history of pains70, 742 plus psychic vulnerability or mental illness376, 468. The studies are summarised in appendix
3 (table 3).
Discussion
Some of the works mentioned above have been collated in a meta-analysis 414,
which concluded that there was some sort of interrelationship between
gallstones and severe upper abdominal pains. However, none of the surveys were ideal because they did not properly identify symptoms specific
to stones in the gallbladder, so it is difficult to reach an unambiguous conclusion. The screening studies constitute snapshots of the general population, so a high incidence of disease was not expected. These surveys do
not, therefore, reflect the clinical working day. Studies of groups of patients referred to a clinical department or to an X-ray department may
also be an inadequate way of studying gallstone symptoms, as the patients
have been pre-selected on the basis of symptoms that suggest bile disease.
To a certain extent, clinical series studying persistent pains may identify
which symptoms are not associated with gallstones by focusing on patterns of symptoms that most commonly cause persistent pain. However,
abdominal symptoms vary greatly382, so the findings are ambiguous. A
more definitive answer would be found, if a group of patients with gallstones and upper abdominal pains was randomised for either cholecystectomy or no treatment. Such a survey has been conducted721, but it had
major in-built problems in the form of large-scale exclusions (63%) and a
high drop-out rate after the randomisation (12-24%). The results of the
survey have not yet been published.
Whenever scientific studies fail to provide unambiguous answers, there
is a tradition of delineating the area at consensus conferences. These conferences have defined gallstone pains as “a relatively strong pain that occurs in attacs, is located in the epigastrium or in the upper right quadrant,
lasts 1-5 hours and often wakes the patient during the night”45. Even
62
though the literature search have demonstrated a significant relationship
between this pattern of symptoms and the incidence of gallstones, the results can only be used in the clinical working day with the proviso that
these pains are also experienced by people without gallstones. In the Danish cohort surveys, 2.7% of the population suffered from attacks of severe
pains that lasted for hours in the epigastrium or upper right quadrant, regardless of whether or not they had gallstones368, 371. An Italian study 53
revealed that 5% of Italian men and 8% of women have “gallstone pains”
without gallstones. Gallstone pains in the Italian studies were defined as
“pains in the epigastrium or upper right quadrant within the last five
years. The pains must last more than half an hour and must not be eased
by bowel movements/wind”.
Conclusions
❖
Hour-long bouts of severe pains in the upper abdomen (the top of the stomach or
upper right quadrant) may be associated with gallstones. The pain starts relatively abruptly and occasionally radiates towards the back. This corresponds more
or less to the symptoms described in the early literature. These symptoms are relatively rare. The symptoms do, however, also occur in people without gallstones, so
it is impossible to define exactly when these symptoms are due to gallstones and
when they are not.
❖
Other abdominal pains are probably not due to gallstones.
❖
Dyspepsia is not caused by gallstones (see section 5.4.1; page 85).
5.3
I NDICATION FOR TREATMENT
Pains are the main indication for treating stones in the gallbladder. The
problems listed above that are associated with identifying symptoms specific to stones in the gallbladder explains why the indication for the treatment of patients with gallstones has always been open to debate. The father of modern cholecystectomy, Langenbuch, is supposed to have said:
“In my opinion, cholecystectomy should be used in cases where both patient and doctor have exhausted their patience.”
The regional variations in cholecystectomy rates documented in this
report reflect the fact that relationships between gallstones and symptoms
are open to interpretation, as the individual doctor and patient have different opinions about when a symptom is due to gallstones – it is also possible that they have different levels of patience. The differences in indication should also be considered in a historical and international light:
63
❖
Historically, treatment has changed. A Danish autopsy study showed that the proportion operated for gallstone disorders rose from 2-3% in 1920 to 40% in 1985 772.
❖
A systematic study of the literature covering screening surveys of random samples
of the population, in which the cholecystectomy rate for people with gallstone disorders (both people with gallstones and those who had a cholecystectomy ) was
estimated, revealed that the rates vary among men from 5-36% and among women from 5-55%. In other words, in some countries (Norway) only 5% of those
who have gallstones are operated on, while in other countries (USA, Italy, Sweden)
more than 50% have an operation. In addition, women are treated for gallstones
far more often than men. It is unlikely that these pronounced variations can be explained solely by different symptoms. They have to be ascribed to different attitudes – among both patients and doctors – to when a patient should be examined
and treated for gallstones. A summary of these studies is included in appendix 3
(table 4).
Consensus
A number of attempts have been made to reach a consensus about the indication for cholecystectomy. A model with two consensus panels – one
consisting of nine surgeons and one consisting of various specialists (surgeons, medical gastroenterologists, internal physicians, general practitioners and radiologists) was developed in the USA720 and later tested in
Israel242, 243, 244 and Great Britain699. On the basis of the available literature,
a number of patient histories were drawn up regarding gallstone disorders.
Each member of the panels had first to assess each patient history themselves, after which the panel attempted to reach an agreement about a treatment indication. In general, the surgical panel was more disposed
to find indications for cholecystectomy than the mixed panel. In almost
half of the patient histories, agreement could not be reached within the
panels699. There was, however, general agreement that people with asymptomatic gallstones or vague symptoms should not undergo a cholecystectomy, whereas people with stones in the gallbladder and one or more attack
of gallstone pains should be offered a cholecystectomy. The indication
for cholecystectomy fell with increased incidence of co-morbidity in the
patient377. These recommendations correspond to international recommendations44, 45, 46. This represents a significant tightening up in relation to
the recommendations of earlier consensus panels who tended to agree that
operations should be offered to patients with gallstones and dyspepsia
(without pains)805.
64
Audit
Only one single study700 looked at the extent to which indications for
cholecystectomy provided by the above-mentioned consensus are observed in daily life. Information was extracted from journals on 252 patients, who had had a cholecystectomy and the information was compared
with the above-mentioned panel consensus 699. The panel consisting of
different specialists would have agreed on operation for 41% of cases and
no operation for 30%. The corresponding figures for the surgical panel
would have been 52% and 2%. In the remaining cases (29% and 46%,
respectively) it would not have been possible to reach a consensus. It
proved impossible to find publications dealing with audits of gallstone
treatment in Denmark.
Even though a consensus has been reached about indications for cholecystectomy, it can be difficult to comply with in daily life. One study revealed that if a computer program with recommendations for cholecystectomy was used simultaneous with indication for operation, the recommendations were followed far more often than before the computer programme was used102.
Discussion
In contrast to medicinal treatment, in which the effect of a chemical substance can be tested and subsequently stopped if it does not work, a cholecystectomy is non-reversible. Thus, there is good reason to warn against the
so-called “diagnostic cholecystectomy” in which the gallbladder is removed
to see whether or not it caused the symptoms 730. If a patient suffers symptoms, then the patient and doctor must decide when they are so troublesome
that treatment ought to be offered. Even if a symptom is thought to be associated with gallstones, it is not necessarily an indication for treatment.
This depends on a number of things, such as the patient’s wishes, fear of new
attacks, etc. The patient’s overall health also plays a role. Observation of a
patient after the first pains seems justifiable, since the spontaneous course of
stones in the gallbladder is relatively peaceful (see section 3,2).
Conclusion
❖
Despite attempts to reach international consensus, a great deal of disagreement
still surrounds cholecystectomy indications.
❖
A discrepancy exists between the indications for cholecystectomy defined by consensus panels or international recommendations and the indications used under
everyday clinical conditions.
65
❖
Cholecystectomy ought to be limited to patients with the type of pains that the
consensus has defined as being due to stones in the gallbladder.
❖
The large proportion of patients with persistent pains, audit surveys and studies
showing rises in cholecystectomy rates suggest that too many people undergo
cholecystectomy.
5.4
M ETHODS OF TREATMENT
The technologies used to treat patients with symptomatic gallstones are
cholecystectomy, cholecystolithotomy or stone dissolution (ESWL/bile
salts). The primary purpose of the treatment is to remove symptoms, while
the secondary purpose is to remove gallstones. Ideally, the treatment
should not lead to complications or mortality, there should be few postoperative pains, the duration of the stay in hospital and of the convalescence should be short and the cosmetic result satisfactory. The next section compares the individual treatments with these objectives.
5.4.1 Cholecystectomy
The gallbladder can be removed either by traditional open cholecystectomy, cholecystectomy by minilaparotomy or laparoscopic cholecystectomy.
Cure from symptoms
Among the randomised surveys of the different access to cholecystectomy
(appendix 3) only one study dealt with persistent pains505. It revealed no
difference between cholecystectomy by minilaparotomy and laparoscopic
cholecystectomy after 6-12 months as far as the incidence of persistent
pains, the regularity and type of pains or visits to the doctor because of
pains were concerned.
The clinical series (appendix 3, table 3) revealed persistent pains after
cholecystectomy in 7-41% (average 22%) after traditional open cholecystectomy and in 6-37% (average 21%) after laparoscopic cholecystectomy. If the data are restricted to patients who suffer persistent pains of
the same or greater magnitude, the proportion falls to 4-17% (average
8%) after traditional open cholecystectomy and to 3-11% (average 7%)
after laparoscopic cholecystectomy. None of the clinical series concerning
cholecystectomy by minilaparotomy stipulated the proportion suffering
from persistent pains.
These numbers suggest that the degree of persistent pains is probably
not dependent on the size of the incision. This is corroborated by the fact
66
that persistent pains after contusion (ESWL) and after medicinal dissolution of gallstones are the same (6-31%; average 19%) as after cholecystectomy8, 436, 754, 825.
Thus, it can be concluded that the two new access to remove the gallbladder (minilaparotomy and laparoscopy) have not affected the primary
purpose of the treatment.
There has been a longstanding debate among surgeons about the extent
to which a long cysticus stump can cause persistent pains after a cholecystectomy. A randomised survey with an 8-year follow-up359 revealed that
40% of patients had persistent pains after traditional cholecystectomy
compared with 11% in a group that had the whole ductus cysticus removed. The survey was blinded. It is, however, rare for a long cysticus
stump to be the sole explanation for persistent pains646 and no special pattern of pain has been associated with the length of a remaining cysticus
stump864.
Removal of gallstones
Cholecystectomy by traditional open laparotomy and by minilaparotomy
are equally good as far as removal of gallstones (with gallbladder) is concerned. The same can more or less be said about laparoscopic cholecystectomy, but since defects are often made in the gallbladder during dissection357, stones are sometimes lost and left behind in the abdominal cavity357, 399, 765. A number of casuistic studies describe the many ways these
stones manifest themselves in the form of intra-abdominal abscesses616,
ileus594, fistula to the urinary bladder139, fistula to the pulmonary cavity842
and coughing up of stones108. Clinical series show that left stones rarely
cause complications357, 399 but that the individual complications can be serious765.
Time spent in hospital and postoperative pains
No scientific evidence exists to define exactly how long patients ought to
remain in hospital after a cholecystectomy. The median time for elective
simple cholecystectomy fell in Denmark from 11 days in 1978, to 6 days
in 1991, to 3 days in 1995. There was no significant gender difference
(figure 35). The shorter hospital stay was accompanied by a minor rise in
the frequency of readmissions to hospital, as the proportion of patients
readmitted within a month after discharge rose from 9.5 % in 1978-83;
to 11.3% in 1984-87, to 12.1% in 1988-91 and 13.6% in 1992-95. The
reduction in the time spent in hospital in the period before the introduc-
67
tion of laparoscopic cholecystectomy corresponds to the findings in international literature540, 817. The fall does not specifically apply to cholecystectomy, as the time spent in hospital was reduced for ordinary surgical
procedures in general from 9.9 days in 1970, to 5.3 days in 1993540. The
fall may be due to better information, changing attitudes and traditions307,
improved surgical and anaesthesiology techniques and streamlining requirements. It was probably due to a combination of the factors mentioned above.
FIGURE 35
Length of hospital stay for simple elective cholecystectomy
Days
30
28
26
24
22
20
18
16
14
12
10
8
6
4
2
0
Year 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95
Women
Men
One aspect that affects the amount of time spent in hospital is the degree
of post-operative pain, which again depends on surgical trauma. The
trauma is caused by incision into the abdominal wall and by the removal
of the gallbladder. Since the latter is compulsory in all three methods, the
only difference is the incision into the abdominal wall. While there are
clear distinctions between laparoscopic surgery and the open forms, the
transition from minilaparotomy to traditional laparotomy (page 12) is
fluid. However, there is no major difference between the total length of the
incision in laparoscopic surgery (3-4 cm) and in straightforward cholecystectomy through minilaparotomy (3-6 cm). It is open to debate how
much such a small difference can mean to levels of surgical trauma. In one
clinical study of laparoscopic cholecystectomy, patients who had one of
68
the incisions lengthened to remove a large gallbladder (because of inflammation or stones)100, did not take more painkilling medicine than those
who did not have the incision lengthened.
The literature shows that it is not only surgical trauma that affects the
amount of analgesics and the length of hospital stay. The information that
the patient receives about the procedure from the surgeon and the rest of
the medical staff, and which reflects their attitudes to the procedure, is
probably a critical factor241, 536. One study suggested that positive hospital
surroundings reduce the need for painkilling medicine and the length of the
stay in hospital795. A systematic study of the literature showed that by prioritising efforts – including early postoperative feeding and in-depth information – for patients after traditional open cholecystectomy lead to very
low consumption of analgesics and patients being discharged 1-4 days after the operation447, 533, 534, 550, 584, 635. In a clinical series starting in 1980, consecutive patients were offered discharge the day after traditional open
cholecystectomy with a success rate of 92%533. The effect was originally ascribed to early feeding after the operation, but a randomised trial rejected
this241. Since the first reports, several of which exist only as abstracts, five
clinical works have been found in which consecutive patients were discharged quickly after a traditional open cholecystectomy with great success
and low readmission frequency (table 6). A further two examinations
showed that it was possible to treat these patients as outpatients. These examinations are not included in table 6, since it is not known to what extent
they represent consecutive patient material785, 813. What all these works
have in common is that a great deal of effort was invested in informing the
patients about the procedure.
TABLE 6
Clinical series of consecutive patients, in which early discharge is planned after traditional
open cholecystectomy.
Post-operative discharge (cumulated percentages)
Author
Period
N
Same day
Re-admissions
Notes
Hall299
1980-84
100 -
-
51%
-
3.2 dag
0
a)
Saltzstein674
1988-90
500 -
23%
56%
-
2.8 dag
2 (0.4%)
b) d)
Chaudhary132
1986-89
340 -
-
-
86%
Saltzstein675
1990
64
-
-
-
Moss535
1983-87
160 -
100%
-
-
69%
1st day 2nd day 3rd day Average
-
0
a)
< 1 dag
1 (1.6%)
c) d)
1 dag
3 (1.9%)
a)
a) Elective, simple cholecystectomies
b) All patients including acute cholecystitis and choledochal surgery. If the material is restricted to elective simple cholecystectomies in
people under age 35, 44% were discharged after the first day and 83% after the second day
c) Simple cholecystectomies covering both elective and acute patients. Limited to people under 56 years of age
d ) The two groups of patients published by Saltzstein were not the same
69
In the first clinical series studying cholecystectomy by minilaparotomy, the short hospital stay from 1-3 days was emphasised282, 514.532 – and
later, same-day surgery was described in a series of 200 selected patients
discharged 3-10 hours after the operation435.
Clinical series studying laparoscopic cholecystectomy also highlight
the short hospital stay of 1-2 days 43. A number of studies have aimed at
same-day surgery among selected patients427, 619, 696, 747 with a success rate
of 50-100%, and among consecutive patients for simple elective cholecystectomy230, 524, 767, 810, 811 with a corresponding rate of 61-94%.
In other words, it is possible for all three access to cholecystectomy to
send patients home either on the same day or 1-2 days after the operation.
Comparison between forms of access
A reliable comparison of the three access to cholecystectomy, as far as
analgesics and the amount of time spent in hospital are concerned, can
only be conducted in randomised surveys in which patient and staff are
not informed of the method applied582. Of the randomised examinations
comparing laparoscopic cholecystectomy with cholecystectomy by minilaparotomy, only one fulfils this criteria for blinding483 and it showed no
difference in the length of hospital stay. No information was included
about analgesics. Among randomised studies comparing laparoscopic
cholecystectomy with traditional open cholecystectomy, only one lived up
to the criteria for blinding579 and it did not reveal any difference in the
length of hospital stay either, although it did identify more post-operative
pain in the group subjected to open cholecystectomy. The material was,
however, very small (2 x 10 patients).
Among the non-blinded studies, significantly more time was spent in hospital after traditional open laparotomy than after laparoscopy79, 337, 789,
while the results for laparoscopy vs. minilaparotomy500, 504 and minilaparotomy vs. traditional laparotomy574, 703 were ambiguous. The use of analgesics was significantly greater after traditional open laparotomy79, 337, 789
and after minilaparotomy503 than after laparoscopy. No significant difference in the use of analgesics was registered after traditional laparotomy
compared with minilaparotomy574, 690. Table 5 in appendix 3 illustrates
these small differences and since the studies were not blinded and the results, therefore, susceptible to staff and patient attitudes to the different
operations, the results have to be interpreted carefully.
A number of randomised trials revealed a whole string of other circumstances that affect the use of analgesics and the amount of time spent
70
in hospital. They included the location of the incision, transcutaneous
electrical nerve stimulation, epidural anaesthesia, epidural morphine plus
local anaesthesia in the wound, intrapleurally (in the pulmonary cavity),
intraperitoneally (in the abdominal cavity) and intercostally (between the
ribs). Time constraints prohibit this report from studying these interrelationships systematically, but the randomised surveys are listed in appendix 3.
Conclusion
The amount of time spent in hospital after cholecystectomy has fallen
steadily since 1978. The literature suggests that the length of the stay in
hospital depends on factors other than just surgical trauma. Even if the
amount of time spent in hospital fell after the introduction of laparoscopic
cholecystectomy, no documentary evidence exists to prove that the fall
was caused by the laparoscopic procedure. As far as the use of postoperative analgesics is concerned, laparoscopic cholecystectomy seems to be a
minor improvement over open surgery. However, analgesics are taken for
such a short time that it ought not to affect the choice of procedure.
Complications to Cholecystectomy
The vast majority of cholecystectomy complications are banal. Among the
more serious complications, such as lesions of the bile ducts, major arteries and the gastrointestinal tract, the former is by far the most common333
and this section will concentrate on them.
International literature states that the introduction of laparoscopic
cholecystectomy led to a rise in the number of bile duct lesions and that
there may even be a reason to fear underreporting471, 756, 848. Many researchers have attributed the rise in complications to insufficient training
of surgeons who felt pressurised to start using the new method too soon137,
165
and consequently, there was an initial call for caution. One Danish consensus report37 states that the number of bile duct lesions during laparoscopic surgery in Denmark is no higher than the number of lesions suffered during traditional open cholecystectomy on Funen in 1953-57477.
The data has not been compared with more recent material.
The next two chapters study the available literature in greater depth
and assess the extent to which lesions of the bile ducts have increased in
Denmark after the introduction of laparoscopic cholecystectomy. Wherever possible, a differentiation is made between:
71
❖
peripheral lesions (cysticus leak, leak from aberrant/accessory bile duct, unidentifiable leak), which either leads to re-operation, ERCP with the insertion of a stent
or percutaneous drainage. These lesions are not serious enough to cause lasting
damage to the bile ducts per se.
❖
central lesions, which involve the deep bile ducts (ductus choledochus, ductus hepaticus communis and ductus hepaticus dxt. and sin.). Lesions of these organs can
cause lasting damage to the bile ducts in the form of contraction and impaired
liver function.
Analysis of bile duct lesions – literature review
The literature was studied systematically on the basis of the principles discussed in appendix 3. The summary of the various complications considered:
❖
all randomised trials
❖
all surveys of all cholecystectomies in well-defined geographical areas during the
period when laparoscopy was being introduced
❖
all consecutive series of over 200 patients in which the operations were performed
after 1978 (see, however, page 75).
Randomised surveys
The randomised surveys were too small to evaluate differences in complication rates accurately. A total of 500 patients were covered by randomised surveys comparing laparoscopic cholecystectomy with cholecystectomy by minilaparotomy483, 504. There were two central bile duct lesions
in each treatment group and three peripheral lesions in the laparoscopic
group against one in the minilaparotomy group. The total of three bile
duct lesions in the minilaparotomy group (1.2%) and five in the laparoscopy group (2.0%) was not significant. The very high complication
rate was due to one of the studies, which accounted for seven of the eight
lesions504. There is a temptation to suspect that the surgeons involved in
that study were not trained in minilaparotomy; at any rate it is not obvious from the article. This in contrast to the study with the low complication rate483, which specifically mentioned that the surgeons were trained in both procedures before the survey started. Among 151 patients
randomised for laparoscopic cholecystectomy or traditional open cholecystectomy79, 337, 579, 789 there was one peripheral bile duct lesion in the
open group, but none in the laparoscopic group. Of 341 patients rando-
72
mised for cholecystectomy by traditional laparotomy or minilaparotomy574, 690, 703, there were no reports of bile duct lesions.
All cholecystectomies in well-defined geographic areas
By calculating the complication rate after all cholecystectomies in well-defined geographic areas during the period when laparoscopic cholecystectomy was introduced, the importance of the introduction of the new technology can be calculated.
TABLE 7
The complication rate per year for all cholecystectomies.
Bile duct lesions
1989
1990
1991
1992
1993
N/yeara
Country
b, 149
0.30
0.40
0.80
1.15
0.93
23964
Canada
Russellc, 658
0.04
0.07
0.24
0.27
0.11
6042
Author
Cohen
USA
a: Number of cholecystectomies per year
b: The state of Ontario in Canada. 1989=1989-90 etc. Laparoscopy was introduced 1990-91
c: : The state of Connecticut, USA. Laparoscopy was introduced in 1990. Breakdown from a laparoscopic register (ending September 93,
so underreporting in the final year is possible). In general, underreporting is possible, since “major bile duct injuries” are defined on
the basis of particular treatment codes and subsequent questionnaires sent to the departments.
Only two articles were identified (table 7). Both reveal a noticeable rise in
the number of bile duct lesions after the introduction of laparoscopic
cholecystectomy. The number of bile duct lesions is highest at the start of
the laparoscopic period, after which there was a fall but not to the level
that existed before the introduction of laparoscopic cholecystectomy. The
two works are supported by a central registration of all bile duct lesions
in New York82, which shows a rise from one registered major bile duct lesion in 1988 (the last year before laparoscopic cholecystectomy) to 21 per
annum in 1990-92. In Australia, the proportion of accidents (medical and
surgical accidents, postoperative complications, side effects of treatment
and unintentional poisoning) associated with cholecystectomy rose by
37.5% in the period 1987/88 to 1993/943.
Clinical series
This section looks at clinical series comparing complication rates between the different methods of access to cholecystectomy. There are two
fundamental problems associated with this comparison:
❖
Clinical series on open traditional cholecystectomy normally includes all cholecystectomies in a given period, whereas clinical series on the laparoscopic and
minilaparotomy access to cholecystectomy only includes selected groups of
73
patients, leaving a group of patients, who are cholecystectomised by traditional
laparotomy. This latter group of patients both have a more advanced stage of
their gallstone disease 378 and more co-morbidity 225,378 compared to the group operated on by the laparoscopic method. This means that, when clinical series of cholecystectomy by minilaparotomy or laparoscopy are compared with clinical series
where a traditional laparotomy is used, a group of more healthy patient are compared with a group of more ill patients,
❖
Before introduction of the laparoscopic technique cholecystectomy was performed by younger surgeons in contrast to the laparoscopic operations, which
mostly is performed by more senior surgeons 682,692. Also in the comparisons between cholecystectomy by laparoscopy and minilaparotomy the distribution of
senior surgeons is in favour of laparoscopy 190,500.
Due to these two problems, it must be expected – à priori – that patients
should experience less complications in the clinical series of cholecystectomy by minilaparotomy and laparoscopy compared to the clinical series
of cholecystectomy by traditional laparotomy.
Before the era of laparoscopic cholecystectomy very few articles dealt
with complications in relation to cholecystectomy, whereas after the introduction several articles and reviews on complications to cholecystectomy emerged. In the following review only clinical series on traditional
cholecystectomy in the period 1978-1990 were included. This restriction
is done in order to include only clinical series as close to the laparoscopic
era as possible, as elder series represent another time with another organisation, which hardly can be compared with the 90’ies. The lower limit of
1978 was chosen, as it from this year is possible to compare with Danish
data from the National Hospital Discharge Registry and as the relative
long period (13 years) will make it possible to have sufficient material.
Open cholecystectomies after 1990 are not included, as many countries at
that time had started laparoscopic surgery, making cholecystectomies performed by traditional laparotomy a selected group. This was evident from
the two-fold rise in postoperative mortality after open traditional cholecystectomy after 1990745. The review of open traditional cholecystectomy
is divided into series only including simple cholecystectomies (or where it
was possible to extract these operations from larger series also including
cholecystectomy with bile duct surgery) and series, where it was not possible to distinguish between simple cholecystectomy and cholecystectomy
with bile duct surgery. The former series are more comparable with series
on laparoscopy and minilaparotomy than the latter.
74
As very few series have been published on cholecystectomy by minilaparotomy, all series are included independent on number of operations
and when the surgery was done. Separate analyses are, however, performed of series representing more than 50, more than 100 and more than
200 patients. Two studies being part of randomised trials in comparison
with laparoscopic cholecystectomy are not included in this review, but
dealt with elsewhere in this report.
Literature on clinical series including laparoscopic cholecystectomies is
huge. To minimise the work only articles published in an early period
(1990-1992) and a late period (1995-97) are included. Besides clinical series, results from questionnaire reviews, registers and audit are included.
A summarised review concerning bile duct lesions is shown in table 8,
whereas results for each study is shown in appendix 3 (table 6-13). Central bile duct lesions are far more common in the laparoscopic series compared to traditional laparotomy and minilaparotomy, whereas the difference in periferal bile duct lesions are not than big.
TABLE 8
Total summary of central and peripheral biliary tract lesions in materials consisting of 200(+)
consecutive patients operated since 1978 a.
Access to cholecystectomy
Number of
studies
Number of
patients b
Lesions of the bile ducts
Central %
Peripheral
(95% c.l.)
% (95% c.l.)
Open (simple cholecystectomy)
10
4,804
0.04 (0.01-0.18)
0.26 (0.15-0.47)
Open (all cholecystectomies) c
18
15,208
0.13 (0.08-0.20)
0.10 (0.06-0.16)
Minilaparotomy >=50 ptt./serie
16
3,553
0.03 (0.00-0.20)
0.17 (0.08-0.38)
Minilaparotomy >=100 ptt./serie
7
2,921
0.03 (0.00-0.24)
0.21 (0.09-0.46)
Minilaparotomy >=200 ptt./serie
3
2,307
0.04 (0.01-0.31)
0.04 (0.01-0.31)
Laparoscopic (1990-92)
47
19,234
0.32 (0.25-0.41)
0.46 (0.39-0.59)
Laparoscopic (1995-97)
26
24,342
0.26 (0.20-0.33)
0.39 (0.32-0.48)
Laparoscopic (questionnaires)
15
130,320
0.37 (0.34-0.40)
0.30 (0.27-0.33)
Laparoscopic (register)
16
110,939
0.47 (0.43-0.51)
0.28 (0.25-0.31)
6
22,671
0.52 (0.43-0.62)
0.57 (0.48-0.68)
Laparoscopic (audit)
a: : The material for cholecystectomy by minilaparotomy consists of 50, 100, and 200+ patients
b: States the number of patients about whom information is available concerning central bile duct lesions. When calculating confidence
limits for peripheral bile duct lesions, only the number of patients is used about whom information concerning this type of lesion is
available (table 6-13, appendix 3)
c: Including choledochal surgery
Assessment of bile duct lesions in Denmark 1978-95
By using the material used to validate the National Hospital Discharge Register (see section 2.1.2), an assessment was made of developments in bile
75
duct lesions in Denmark from 1978-95. Courses of treatment, during which
the patient – after an initial admission for cholecystectomy with or without
bile duct surgery – was readmitted or transferred to another department for
endoscopic or open biliary tract surgery, must be presumed to include the
majority of patients who have suffered a lesion of the bile ducts. These
courses of treatment rose fourfold after the introduction of laparoscopic
cholecystectomy (figure 36, page 77). All commentaries on these courses of
treatment together with a random cross-section of all other commentaries
in 1979, 1985 and 1993 were requisitioned from the surgical departments.
The detailed breakdown is covered on page 22 and in appendix 2.
In approximately 1/3 of the cases, the treatments in figure 36 represented
lesions of the bile ducts during simple cholecystectomy. This proportion remained constant throughout the whole period. More or less all the other
cases involved patients who subsequently had a stone removed from the bile
ducts or were treated for biliary tract dyskinesia (page 83). By counting the
number of bile duct lesions found in the commentaries received and predicting the same regularity of bile duct lesions in commentaries not received, the
annual frequency of bile duct lesions was calculated for patients who had a
simple cholecystectomy. In order to achieve reasonable quantities of data, the
period was divided into three sub-periods, of which the final period includes
all the years during which laparoscopic cholecystectomy has been performed
in Denmark, while the first period is divided into two equally large halves.
The bile duct lesions are divided into central and peripheral according to the
same principle described under the literature survey (page 72).
Because of size of the random sample, the data has to be interpreted
carefully, but the calculations suggest that there has been a two- to threefold increase in the number of central lesions, while the number of peripheral lesions has multiplied since the introduction of laparoscopic technology (table 9).
TABLE 9
The estimated incidence of bile duct lesions during simple cholecystectomy in Danish
hospitals, 1978-95.
Localisation of bile duct lesion
Peripheral
Central
Uncertain*
Total
Period
% (95% c.l.)
% (95% c.l.)
% (95% c.l.)
% (95% c.l.)
1978-83
0.02 (0.01-0.06)
0.16 (0.11-0.23)
0.00 (0.00-0.02)
0.18 (0.13-0.25)
1984-90
0.04 (0.02-0.08)
0.11 (0.07-0.16)
0.01 (0.00-0.04)
0.15 (0.11-0.22)
1991-95
0.39 (0.31-0.51)
0.33 (0.25-0.44)
0.10 (0.06-0.17)
0.83 (0.70-0.99)
* The medical commentaries did not specify peripheral or central.
76
FIGURE 36
Complicated courses after simple cholecystectomy
Percent
4
3
2
1
0
Year 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95
The data in table 9 is underestimated. During the study of the commentaries from the random extract from 1979, 1985 and 1993 a further four
complications were identified: one in 1979, one in 1985 and two in 1993.
This may explain some of the discrepancy between the results in this report for 1991-95 and the breakdown of central bile duct lesions from the
laparoscopic register in Denmark, in which the percentage is 0.74%10.
Another possible explanation is that the results from the laparoscopic register only include patients who had a laparoscopic cholecystectomy. The
results show that this screening method using patients causes covering
multiple admissions will identify many of bile duct injuries, but that there
is a certain amount of underreporting.
Discussion
The data on complications after traditional open cholecystectomy is confirmed by a number of studies of major series (3,403 to approx. 90,000 patients), which show a bile duct lesions frequency of 0.05-0.07%29, 163, 268.
However, the articles do not contain enough details to be included in the
total result for all clinical series. In one review502, the proportion of bile
duct lesions after traditional open cholecystectomy was estimated at
0.2%. The work lacks a number of articles, includes older series, includes
series after the introduction of laparoscopic cholecystectomy and includes
77
a major register study that overestimates the complication rate, since it
does not differentiate between bile duct lesions and other peroperative lesions to the gastrointestinal system. Review articles about bile duct lesions
after laparoscopic cholecystectomy using criteria other than those used in
this study, or in which the criteria are not mentioned at all, show numbers
corresponding to the result of this survey, with bile duct lesions ranging
from 0.30-0.63%333, 391, 502. In a 1991 national questionnaire survey in the
Netherlands with an response rate of 88%287, bile duct lesions were found
in 0.51% of open and 1.09% of laparoscopic surgery. Both rates are significantly higher than the results in table 8, which is partly explained in
the case of the open operations by the fact that 15% also had bile duct
surgery and that those who had a traditional open cholecystectomy during the laparoscopic era were at more advanced stages of illness378.
There was no significant difference in complication rates between traditional open cholecystectomy and cholecystectomy by minilaparotomy.
The data for minilaparotomy is, however, small and one major French series197 in particular is very poorly described. It is, however, conspicuous
that none of the clinical series reveal the high incidences of lesions seen in
the laparoscopic series.
Clinical series, questionnaire surveys and register studies have all been
criticised for underreporting bile duct lesions471, 756, 848 compared with an
audit, in which an unbiased panel studies all the available patient journals.
This report (table 8) partially supports this criticism, as the incidence of
both central and peripheral bile duct lesions is somewhat higher in the audit series than in the other series concerning laparoscopic cholecystectomy. No audit studies were found of cholecystectomy by traditional open
surgery or minilaparotomy.
The rise in bile duct lesions has to be compared with the fact that the
surgeons performing biliary tract procedures in the laparoscopic period
are more experienced than in the period before the introduction of laparoscopy682, 692.
None of the applied methods are ideal for calculating the frequency of
bile duct lesions. This would require a clinical database of all biliary tract
treatments (not just laparoscopic cholecystectomy) listed systematically
according to criteria fixed in advance. Thus, it must be expected that all
the figures shown underestimate the real incidence of bile duct lesions.
However, the calculations have been made the same way, so the registered
rise can be assumed to reflect reality.
78
It has been stated that the frequency of bile duct lesions after laparoscopic cholecystectomy falls over time, a fact partly confirmed by the clinical series in table 8 and the summary in table 7. However, the frequency
of bile duct lesions does not fall to the level experienced before the introduction of laparoscopic cholecystectomy149, 658. Data from the Danish laparoscopic register shows that there has not been any reduction in the
number of bile duct lesions in Denmark in the period 1991-94 among patients who had a laparoscopic cholecystectomy10.
A survey by an intensive care unit showed that complications after laparoscopic cholecystectomy are more severe than after cholecystectomy
by minilaparotomy or traditional laparotomy515.
Conclusion
❖
The expected fall in the number of complications (due to the pre-selection of patients and more experienced surgeons) after the introduction of laparoscopic cholecystectomy did not occur - on the contrary, there was a noticeable rise which corresponds to the international literature.
❖
In several studies, the complication rate fell again after a couple of years but never
to the same low level as before the introduction of laparoscopic cholecystectomy.
No fall was registered in Denmark.
❖
Data from the National Hospital Discharge Register together with findings from
the literature survey provide ample evidence that there was also an increase in
complication rates in Denmark after the introduction of laparoscopic surgery.
❖
The extent to which cholecystectomy by minilaparotomy leads to a lower frequency of bile duct lesions than laparoscopic cholecystectomy cannot be calculated
definitively. The available clinical series suggest that this is the case, but the quality of the series is poor. The randomised studies also show a tendency towards
fewer bile duct lesions during minilaparotomy, but the series are small. However,
there is no evidence to suggest that the minilaparotomy leads to a greater number of bile duct lesions than laparoscopic cholecystectomy.
Convalescence
There is no scientific definition for how long a patient should stay off
work after an operation. A survey of patients who had a cholecystectomy
at Copenhagen University Hospital from 1980-81480 showed median sick
leave of 25-65 days, dependent on the physical nature of the work. A randomised survey of patients operated for inguinal hernia showed that it
was possible to encourage a group of patients to return to work signifi-
79
cantly faster by simply asking them to – without any adverse effects on the
results of the operation103. Corresponding surveys for cholecystectomy patients were not traced.
When laparoscopic cholecystectomy was introduced, short convalescence was stressed as one of the major advantages166, and one Danish survey11 puts the median time for resumption of normal activities at 8 days
(range 1-165). These conditions are, however, not unique for laparoscopic
cholecystectomy. After ambulatory traditional open cholecystectomy, the
patients were able to return to work after 7-12 days675, 813 and in series covering cholecystectomy by minilaparotomy, patients were able to return to
work after 4-5 days if they had a non-physical job and after 21 days if they
had a highly physical job435.
A reliable comparison of the length of convalescence after the different
methods of cholecystectomy can only be conducted by means of randomised surveys in which both patients and staff are blinded as far as the
method is concerned. However, it would be difficult to blind an operation
totally until the end of a period of convalescence since this would involve
the patient not removing the dressing for several days. Two randomised surveys comparing minilaparotomy with laparoscopy483, 504 showed no significant difference in the length of convalescence (table 5, appendix 3), whereas
randomised studies comparing traditional open and laparoscopic cholecystectomy79, 789 revealed significantly longer convalescence in the open group.
Conclusion
The clinical series divulge that informed and motivated patients can return
to work quickly, even after traditional open cholecystectomy. The randomised examinations disclosed no differences between laparoscopic
cholecystectomy or cholecystectomy by minilaparotomy but longer convalescence after traditional open cholecystectomy. These studies were,
however, not blinded, so it is impossible to decide the extent to which it is
the laparoscopic procedure or the attitudes of the staff and patients that
has made the convalescence shorter.
Mortality
The 30-day mortality rate after a simple cholecystectomy is increased
compared with the general population106. Only rarely is this excess mortality directly related to biliary tract disease. It is ascribed to a combination of co-morbidity and surgical trauma. Since laparoscopic surgery has
been regarded as less traumatic than traditional open cholecystectomy, a
80
fall in mortality might have been expected when the technology was introduced.
Mortality rates, 1978-1995
Data from the National Hospital Discharge Register discloses no major
fluctuations in the 30-day mortality rate after simple cholecystectomy for
either elective simple cholecystectomy or all simple cholecystectomies (figures 37). In analyses that make allowances for the presence of other medical conditions (measured as the number of diagnoses registered at the index admission), the mortality rate is significantly higher in the last three
sub-periods compared with 1978-83 as far as all simple cholecystectomies
are concerned (table 10). The increased mortality rate refers primarily to
patients with acute cholecystitis. No reduction in mortality can be detected after the introduction of laparoscopic cholecystectomy.
TABLE 10
The 30-day mortality rate a after simple cholecystectomy in relation to diagnosis and period of
time in Denmark in 1978-95. Only patients with biliary tract diagnoses were included and in
the logistic regression analysis account was taken of age, gender and co-morbidity (number of
diagnoses)
Simple cholecystectomy as index operation
Elective operation
Acute cholecystitis
Total
Period
OR (95% c.l.)
OR (95% c.l.)
OR (95% c.l.)
1978-1983
1.00
1.00
1.00
1984-1987
1.44 (1.09-1.89)
1.44 (1.07-1.94)
1.41 (1.17-1.70)
1988-1991
1.10 (0.79-1.53)
1.48 (1.08-2.03)
1.42 (1.16-1.74)
1992-1995b
1.03 (0.71-1.51)
1.85 (1.34-2.57)
1.62 (1.31-2.00)
a: Mortality is measured from the date of admission, as the actual date of operation is not stipulated in the National Hospital Discharge
Register
b: Some elective patients may have been given the wrong codes and been registered as having acute cholecystitis in 1994-95 (page 93).
Discussion
It is difficult to compare the Danish mortality figures with the literature
for the following reasons:
❖
As a rule, mortality is listed during the stay in hospital, and since the time spent in hospital has fallen throughout the last 20 years, the mortality rate will be lower per se.
❖
It is rare to find works that standardise mortality according to age, gender, general medical condition and how advanced the gallstone disease actually is. After
the introduction of laparoscopic surgery, the proportion of young women has
risen, which will lower the mortality rate per se.
81
FIGURE 37
The 30-day mortality rate after simple cholecystectomy standardised for gender and age
Number per 1,000
40
35
30
25
20
15
10
5
0
Year 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95
Total
Acute
Elective
Thus, none of the available studies are directly comparable with the mortality data in this study for the period 1978 to 1990. Roos648 detects a
slight rise in the age and gender-standardised 90-day mortality rate from
1977-8 to 1982-3, while an older Swedish study128 detects a fall in standardised mortality until 1981 but does not stipulate a post-operative time
frame. In the period around the introduction of laparoscopic cholecystectomy, the mortality rate fell in some studies213, 577, 745, while it rose slightly
in one of the others554. All these works either omit relevant parameters in
the standardisation of the mortality rates or list only mortality during
stays in hospital. Only one work, which calculated the 30-day mortality
and performed a standardisation, was comparable with the Danish
data149. Like the Danish data, this work revealed no significant changes in
mortality rates from 1989 to 1993 (table 11).
The reason why the introduction of laparoscopic surgery did not lead
to a fall in the 30-day mortality may be that the increased complications
rate after the introduction of laparoscopic cholecystectomy counters the
expected fall in the mortality rate, or that the difference in the levels of surgical trauma between laparoscopic surgery and traditional open cholecystectomy is not significant enough to effect the mortality rate.
82
TABLE 11
The 30-day mortality rate after simple cholecystectomy in Canada and Denmark. The estimates
are standardised for age, gender and co-morbidity
Canada149
Denmark
OR (95% c.l.)
OR (95% c.l.)
1989
1.00
1.00
1990
0.84 (0.57-1.24)a
1.38 (0.84-2.27)
1991
0.89 (0.59-1.32)
1.02 (0.59-1.74)a
1992
1.03 (0.68-1.56)
1.18 (0.70-2.01)
1993
1.10 (0.72-1.69)
1.21 (0.71-2.07)
1994
-
1.65 (0.99-2.74)
1995
-
1.29 (0.75-2.22)
Period
a: The year laparoscopic cholecystectomy was introduced
Conclusion
There was an inexplicable and significant rise in the 30-day mortality rate
after simple cholecystectomy at the start of the period, after which the rate
has remained more or less constant. There was no fall in mortality rates
in Denmark after the introduction of laparoscopic cholecystectomy,
which corresponds with international literature on the topic.
Sequela after cholecystectomy
The normal physiological mechanism by which the release of the hormone
cholecystokinin is stimulated by food in the duodenum and makes the
gallbladder contract, the sphincter Oddi relax and the pylorus close –
mechanisms that allow bile to pass from the gallbladder down to the food
in the intestines – do not function after a cholecystectomy. The question is
whether this drastic change of normal physiological conditions causes side
effects.
Post-cholecystectomy syndrome (pains after cholecystectomy)
Persistent pains are suffered by a large number of patients after cholecystectomy (see section 5.2). In a smaller group, the pain is so severe that further examination and treatment is necessary. It is generally agreed that
ERCP can play a central role in diagnosing these pains127, 188, 488, 713, mainly
to examine whether choledochal stones have been left behind in the patient and are causing the pains. It has been suggested that patients with no
sign of stones in the bile ducts but with continued pains may be suffering
from disfunction of sphincter Oddi. The extent to which the pains that led
to the cholecystectomy, were originally due to sphincter disfunction and
83
not gallstones has never been studied in-depth, but it is known that a proportion of gallstone patients experience abnormal sphincter pressure before a cholecystectomy439. Due to the altered physiological conditions after a cholecystectomy, it could also be argued that the disfunction may
arise as a result of the cholecystectomy.
The condition is classified in three groups: Groups 1 and 2 exhibit
quantifiable changes in liver function and bile duct to a greater or lesser
degree, while group 3 only suffer pains332. The dysfunction can be diagnosed either by invasive methods (measuring pressure during ERCP) or noninvasive methods (scintigraphy)439. Few surveys have compared the methods
and found that they agree in the classification of the patients599, 726. The area
requires further research in order to standardise the diagnostic methods.
There are no fixed guidelines for the treatment of these patients. Since
the condition is unpleasant, but not dangerous, it is suggested that medicinal treatment be tried first439. Individual studies have shown effect
of calcium channel blockers294, 396, 678, nitrate60 and lipid-lowering substances (statins)661. Two of the works were randomised trials396, 678. When
medical treatment has no effect, ERCP with sphincterotomy may be tried.
A number of clinical series studying the effect of sphincterotomy show
that pains persists in 12-92%101, 104, 259, 555, 644, 647, 826, 829 of patients. One
work differentiates between the different groups suffering from the dysfunction and finds that the effect on group 3 (those who only have pains)
is very low (92% persistent pains), while it is better for group 2 (40% persistent pains). In a randomised trials269 in which only some patients were
given a sphincterotomy, sphincterotomy was seen to have a positive effect
on pains. A corresponding study has allegedly been conducted but not yet
published260.
There is a potential risk of sphincterotomy spreading in an unsystematic fashion in the event of post-cholecystectomy pains, as more departments master ERCP technology than master the technology for properly
examining bile duct dysfunction. Often the clinical situation is that ERCP
is performed on a patient with post-cholecystectomy pains to search for
residual choledochal stones. If no stones are found, it may perhaps be
tempting to conduct a sphincterotomy now – while the scope is in place –
to avoid subjecting the patient to yet another unpleasant examination.
However, sphincterotomy in this patient category is associated with a significant number of complications (see section 7.3.2) and the effect on the
pains is dependent on the patient being thoroughly examined and treated
in accordance with the diagnosis reached.
84
Within the time scale of this report, it would be impossible to conduct
an in-depth study of this aspect. It must simply be ascertained that there
are no fixed guidelines for this area and that the literature is now so extensive that the subject would make a relevant theme for a health technology assessment of its own, so that guidelines could be established for
how this technology should be used in Danish hospitals in the future
Changes in bile reflux (flowback of bile in the stomach and oesophagus)
With exception of a single study460, population studies that have screened
for gallstones have detected a significantly higher incidence of dyspepsia
among people who have undergone a cholecystectomy than among those
who have gallstones or a normal gallbladder62, 352, 371, 611, 840. This correlation may be due to the fact that some people underwent a cholecystectomy
because of dyspeptic symptoms (with no effect on the symptoms) but it
may also be due to the fact that the cholecystectomy has caused dyspepsia. Nearly all the studies agree that people with dyspepsia suffer bile reflux significantly more often than people without dyspepsia338, 356, 467, 571, 600,
844
, while a single study depicts this as merely a tendency820. Seventeen
studies were identified that measured the incidence of bile reflux before
and after cholecystectomy48, 124, 134, 218, 219, 338, 353, 388, 461, 462, 463, 464, 466, 475, 549, 653, 820.
Fifteen studies disclosed significant increases in bile reflux after cholecystectomy, one study revealed an insignificant tendency820 and another
found no change338. In the latter work, measurements were taken as early
as nine days after the operation, which may be too soon for reflux to establish itself. The remaining studies took measurements from two to several months after the operation. Some of the works also studied whether
the incidence of gastritis (irritation of the stomach) increased. All of them
confirmed an increase219, 353, 463, 464, 549. No difference was detected in the incidence of bile reflux after traditional open cholecystectomy and laparoscopic cholecystectomy, so the effect has to be ascribed to the lack of a
gallbladder356. Individual studies revealed increased reflux in people with
gallstones48, 124, 466 and a connection between gallstones and dyspepsia460.
This may be due to the fact that the incidence of gallstones sometimes
causes the gallbladder functions to cease, which can, in physiological
terms, correspond to the conditions for a cholecystectomy.
Conclusion
The findings quoted above suggest that cholecystectomy does have some
side effects, which can be particularly troublesome for a small group of
85
patients. This should be taken into consideration before cholecystectomy
is performed.
5.4.2 Cholecystolithotomy
A number of technologies can be used for cholecystolithotomy: traditional
open surgery, minilaparotomy, laparoscopy and percutaneous insertion of
probes with subsequent direct pulverisation with lasers or ultrasound or
immediate dissolution with medical substances. Some of the procedures
can be performed under local anaesthesia.
The National Hospital Discharge Register contains treatment numbers
for these technologies. They account for a total of about 1.6% of all treatments (table 1) with a downward tendency from 1978-95.
Cure from symptoms
No randomised surveys are available to illustrate which of the methods
mentioned above is best as far as the primary purpose of the treatment
–removal of pain – is concerned. Clinical series studying surgical removal
(table 14, appendix 3) on 25 patients or more showed persistent pains after 8-48 months in 5-21%, while series studying 25 patients or more
treated by MTBE show persistent pains after 6-35 months in 7-33% of
cases (table 15, appendix 3).
Removal of gallstones
Surgical procedures remove gallstones with a success rate of 71-100%
(table 14, appendix 3) but stones recur in 5-44% (follow-up 8-236
months). Dissolution by ether has a success rate of 29-96% (table 15, appendix 3) but stones recur in 19-70% (follow-up 6-42 months).
Complications
The complications usually consist of bile leaking from the gallbladder. The
frequency varies from 0-16% in the different series studied (table 14 and
15, appendix 3).
Time spent in hospital, convalescence and mortality rates
These aspects cannot be assessed, partly because of the poor quality of the
available information, partly because the clinical series were very selective
and most of them included extremely sick patients.
86
Discussion
In general, the surveys published cover smaller, selected groups of patients,
especially including patients unable to tolerate general anaesthetics. No
randomised studies have been published in which the technologies used
for cholecystolithotomy are compared with cholecystectomy. The effect
on the primary objective of treatment – absence of pain – is similar to
cholecystectomy. On the other hand, as far as the secondary objective of
the treatment is concerned, i.e. removal of the gallstones, the success rate
is not as high as for cholecystectomy and there is also a great risk of stone
recurrence. The fact that cholecystolithotomy is not so widespread can
thus be associated with the low success rate as far as the removal of gallstones is concerned. However, there is a great deal of evidence to suggest
that stones do not recur in half of the patients and, in the light of the longterm side effects of cholecystectomy, further study is recommended into
whether some patients would find it more beneficial to only have their
gallstones removed. Too few epidemiological surveys exist, however, to
work out which patients are least likely to reproduce stones. A randomised trial should be conducted of this group of patients to compare
cholecystolithotomy with cholecystectomy.
In addition, the method should be refined for the small group of patients who are too sick to tolerate an anaesthetic and who would benefit
from the fact that this method can be used under local anaesthesia.
5.4.3 ESWL/bile salts
Not all gallstone patients can be treated with bile salts. The gallstones
have to be X-Ray negative (i.e. mainly cholesterol stones), must not be
over 15(20) mm485, 672 and the gallbladder has to function. A total of only
10-15% of gallstone patients fulfil these requirements. After the introduction of the use of ESWL (Extracorporeal Shock Wave Lithotripsy) –
originally devised to pulverised kidney stones133 – for stones in the gallbladder in 1985680, it was possible to expand the indication to include
stones of up to 30 mm as long as they did not fill more than 30% of the
biliary-bladder lumen334. After that, it was assessed that approx. 20% of
gallstone patients were suitable for ESWL and bile acid treatment663.
The literature includes several hundred studies of which several are
randomised trials. A systematic study of this literature would per se constitute a comprehensive work. This report uses data from a meta-analysis
of randomised surveys of treatment with bile salts before September
1992493 as well as reviews published since 1991. Thus, an in-depth study
87
of the literature in this area has not been performed except for clinical series describing the incidence of persistent pains after stones have been dissolved.
Cure from symptoms
Persistent pains after ESWL and medical dissolution of gallstones are of
the same extent (6-31%) as after cholecystectomy8, 436, 754, 825. During the
actual treatment – before the stones are dissolved – there is an inexplicable improvement in the symptoms672.
Removal of gallstones
A meta-analysis493 of 23 randomised surveys covering 1,949 patients concluded that the optimal treatment is either ursodoxycholic-acid or a combination of urso- and chenodeoxycholic acid. Combination treatment dissolved 63% of gallstones. If the treatment is combined with ESWL, a
higher success rate is achieved. ESWL alone has a poorer success rate than
ESWL followed by treatment with bile salts47. In one randomised Danish
study, in which there was a low success rate as far as stone dissolution was
concerned, it was concluded that the method was not very suitable47.
After treatment, stones will recur in some patients. The relapse rates
are 31-61% after 5-11 years573, 657, 664, 806. One index article concludes431
that approximately half of the patients suffer a recurrence, the majority of
them during the first five years. Continued treatment with low-dosage ursodeoxycholic acid and anti-inflammatory drugs is suggested to reduce
the risk of stones reforming672. Very few relapses cause symptoms during
the first years431. It proved impossible to find a straightforward epidemiological work that – with correct analyses – attempted to identify in which
patients stones recur with the purpose to improve the selection of patient
for treatment.
Complications that required intervention were limited to gallstone
pancreatitis or cholestasis. These complications occur in 1-2.5% of the
patients and are dealt with by endoscopic procedure665, 693.
Discussion
The literature is comprehensive and nobody has really tried to summarise
it systematically. If we presume that 20% of all gallstone patients are suitable for this treatment, that the treatment is a success in 50% of cases and
that stones recur in 50% of patients within 10 years, then 5% of those
who could be offered operation will experience a lasting effect. A further
88
5% would experience a long-term effect in the form of absence of pain.
The technology is used abroad. However – apart from one Japanese
study794 which suggests that just under 30% of the gallstone patients in
Japan are treated with ESWL and bile salts – no surveys have been identified about how frequently the technology is used. However, the volume of
articles suggests it is widespread in the USA and in certain parts of Europe.
Because of the lack of specific treatment codes in the National Hospital
Discharge Register, the extent of the use of this technology in Denmark
cannot be assessed, but it is probably not widespread31, 47.
Conclusion
The technology is widespread abroad, but has not gained a foothold in
Denmark. In relation to the long-term side effects after cholecystectomy
and the opportunities for early tracing and screening (see section 3.3.2),
this technology and its application in practice ought to be studied in greater
depth.
5.4.4 Comparison between cholecystectomy, cholecystolithotomy and ESWL/bile
salts
No randomised trials were found in which cholecystectomy is compared
with cholecystolithotomy or direct dissolution of stones. Seven publications were identified, in which cholecystectomy was compared with
ESWL/bile salts64, 172, 281, 565, 613, 614, 615. The articles represent three randomised trials64, 565, 613, 614, 615 and two non-randomised172, 281. The randomised trials cover 260 patients, of whom 163 were in one study565. Two
of the studies dealt with traditional open cholecystectomy and had a follow-up of one year, while one64 dealt with laparoscopic cholecystectomy
which had a follow-up of three months. The primary objective of the treatment –removal of pain – was identical in the two treatment groups after
three months in two of the studies64, 565 but significantly lower in the ESWL
group in the third study614. After a year, there was no difference in the incidence of persistent gallstone pains in the two treatment groups565, 614. As
far as other gastrointestinal symptoms were concerned, there were no significant differences between the two groups either64, 565, 614. Severe treatment-related complications occurred with equal regularity in the two treatment groups. The two non-randomised studies172, 281 were not analysed in
greater depth.
Theoretical models (decision analyses) built on available information
about natural history, morbidity and mortality showed that there either is
89
no significant difference in expected mortality when choosing either
cholecystectomy or ESWL722 or a tendency to increased mortality with operations. By using the quality of life of patients as a parameter69, ESWL
can be seen as having a better effect than traditional open cholecystectomy
in people with only one gallstone, but not in young people with multiple
stones69.
Conclusion
As far as the primary purpose of the treatment is concerned –removal of
pain – there does not seem to be any difference between cholecystectomy
and ESWL/bile salts after one year. Longer observation would, however,
be desirable as the people who receive ESWL/bile salts treatment are still
at risk of new/more stones and complications to their stones. Greater indepth study is called for to compare the technologies used to surgically remove or dissolve gallbladder stones with cholecystectomy.
5.4.5 Cholecystectomy for acalculous pains
Even though this report is a health technology assessment of the treatment
of patients with gallstones, it is natural to include the above-mentioned
technology, as it contains several of the aspects that have been reviewed
under indications for gallstone treatment (page 63). This group includes
patients with severe “gallstone-like pains” but without gallstones.
As previously described, a small proportion of the population has
“gallstone-like pains” without having gallstones53, 368, 371. People who suffer this type of pains sufficiently often, will consult their doctor and some
will be offered a cholecystectomy. One randomised survey and more than
20 clinical series were identified, in which patients without gallstones but
with gallstone-like pains had their gallbladder removed (table 16, appendix 3). Summarising the clinical results reveals two things: firstly, the primary purpose of the treatment – removal of pain – is achieved in roughly
the same number of patients as with cholecystectomy for gallstones, with
a variation of persistent pains of 5-33%. Secondly, the surveys suggest –
even though they refer to small, selected groups – that those with a pathological physiological test (reduced emptying of the gallbladder, pains by
contraction) are more likely to benefit from the treatment, than those with
a normally functioning gallbladder. One randomised survey856 covered 21
patients with pains and reduced emptying of the gallbladder, in which half
had a cholecystectomy and the other half serves as a control group. The
90
patients were followed for just under three years with significant improvement in symptoms in those who had a cholecystectomy.
The technology is gaining a foothold and there is a potential risk of
over-treatment if the indication is not precisely defined. From the patient’s
point of view, the rationale seems sensible, since it is abdominal pains –
and not gallstones – that cause discomfort. The extent to which this treatment is used in Denmark is not known. The number of treatments that include simple cholecystectomy but no gallstone diagnosis remained constant from 1978-95 at around 2%.
Conclusion
The technology seems to be relevant for specially selected patients. However, it needs to be tested in further randomised surveys to limit its use in
the treatment of patients without gallstones and with gallstone-like pains.
The use of the technology has to be monitored carefully to avoid overtreatment, which could have serious consequences.
91
6. Treatment of patients with
acute cholecystitis
In the vast majority of cases, acute cholecystitis is caused by stones in the
gallbladder. Acute cholecystitis reflects complications to gallbladder stones.
The disease can be divided into complicated acute cholecystitis (for
example perforation, abscess formation) and uncomplicated acute cholecystitis.
6.1
D EVELOPMENTS IN D ENMARK , 1978-95
The survey of cholecystectomy rates for acute cholecystitis, 1978-95,
(figure 38) was based on patients who had a simple cholecystectomy as
their index operation combined with the diagnosis acute cholecystitis
(appendix 2). In women, there was a rise of 10% (1.1% per annum) from
1978 to 1987, then a fall of 27% (4.5% per annum) to 1993 followed by
a new rise of 42% (21% per annum) until 1995. A corresponding pattern
was revealed in men, albeit less pronounced.
FIGURE 38
Simple cholecystectomy in patients with acute cholecystitis
Rate per 100,000
20
18
16
14
12
10
8
6
4
2
0
Year 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95
Women
92
Men
These curves are different than the curves for simple cholecystectomy for
elective conditions (figure 24). On the basis of the two sets of curves, it can
be calculated that the ratio between acute and elective cholecystectomy
for women has varied from 1:5 in 1978 to 1:4 in 1987, 1:7 in 1993 and
1:4 in 1995. The ratio for men remained more or less constant at 1:2.5.
The curves for age-related cholecystectomy rates (figures 39 & 40) reveal that the rise in cholecystectomy rates for acute cholecystitis among
women until 1987 was mainly due to the increased number of operations
on elderly patients. In the two last sub-periods, the tendency was that
more younger and fewer older patients were operated. The tendency for
the number of operations to peak to a top at 30 was not as pronounced
as it was for elective cholecystectomies (figure 25). No major fluctuations
were revealed for men, apart from fewer cholecystectomies in the elderly
age groups in the final sub-period.
Discussion
The figures do not include all treatments for acute cholecystitis. Some patients also underwent surgery to the bile ducts as well as a cholecystectomy
and a new technology emerged during the period, i.e. ultrasound drainage
of the gallbladder. This operation does not have an independent treatment
code, which is why the treatment does not feature in the National Patient
Discharge Register. Some of these patients were later operated in an elective phase, but for some the drainage was the only treatment, especially in
the case of elderly patients. This may explain the fall in the number of
cholecystectomies for acute cholecystitis in the last two sub-periods among
the elderly. The rise in acute cholecystitis in the last two years is probably
not real, but reflects uncertainty about the use of the new diagnosis codes
(ICD10), which were introduced in 1994. This is supported by the fact
that there was no rise in the proportion of patients admitted acutely (data
not shown).
Developments in Denmark correspond to the international literature, in
which the share of cholecystectomies caused by acute cholecystitis rose before the introduction of laparoscopic cholecystectomy417, 540, 605, and subsequently fell149, 213, 658. The changes may be due to a more conservative attitude towards surgical gallstone treatment in the 80s (figure 24), when the
share of elective operations fell, only to rise again after the introduction of
laparoscopic cholecystectomy.
93
FIGURE 39
Simple cholecystectomy in women with acute cholecystitis
Rate per 100,000
60
50
40
30
20
10
0
Age 0
10
1978-1983
20
30
40
50
60
1988-1991
1984-1987
70
80
1992-1995
FIGURE 40
Simple cholecystectomy in men with acute cholecystitis
Rate per 100,000
60
50
40
30
20
10
0
Age 0
10
1978-1983
94
20
30
1984-1987
40
50
1988-1991
60
70
1992-1995
80
6.2
I NDICATION FOR TREATMENT
In contrast to courses of treatment for gallbladder stones without complications, where the indication is relative, there are always indications for
one or other of the forms of treatment for acute cholecystitis, ranging
from antibiotics to drainage and surgery.
6.3
M ETHODS OF TREATMENT
The primary purpose of treatment is to stop the acute infection. The secondary purpose is to prevent acute cholecystitis from recurring. In this section, there has been a systematic literature search for randomised trials.
The technologies described are:
❖
cholecystectomy
❖
cholecystolithotomy or partial cholecystectomy
❖
drainage with or without dissolution/pulverisation of the stones.
6.3.1 Cholecystectomy
When should patients with acute cholecystitis be operated?
Patients with complications to acute cholecystitis (e.g. perforated cholecystitis) have to be dealt with acutely, whereas different strategies have
been applied to patients with uncomplicated acute cholecystitis.
Sub-acute or elective
For many years, patients with uncomplicated acute cholecystitis have been
treated conservatively (e.g. with antibiotics) until the infection subsided.
Subsequently, patients were offered operations 3-6 months later 120, 205.
However, there were also advocates of operation during the acute phase627.
In the 70s and 80s, a number of randomised surveys were conducted in
which patients with acute cholecystitis either had sub-acute operations (a
few days after the symptoms started) or elective operation later on (3-6
months after the initial symptoms). A total of five works were identified 364,
423, 455, 497, 568
, which all showed that sub-acute operation entails the same
complication and mortality rates as late operation. The early-operation
strategy did, however, lead to a reduced number of days spent in hospital,
shorter convalescence and lower morbidity. A large proportion (15-24%)
of the patients who were operated later found that their cholecystitis
recurred during the waiting period and they had to be re-admitted. An
observational study of all patients with acute cholecystitis in the period
before and after the introduction of the new early-surgery strategy in one
95
department showed that the sub-acute operation strategy was also superior to the late operation strategy in the everyday clinical situation454.
“Timing” of sub-acute cholecystectomy
Thus, it is agreed that patients with uncomplicated acute cholecystitis
ought to be operated sub-acutely during the same admission. However,
the infection must not have been present for too long, since that makes it
technically more difficult to perform the operation89. The literature reveals
disagreement as to when a sub-acute cholecystectomy ought to be performed in order to achieve the lowest complication frequency, since opinions vary from no more than 4 days497 to 7 days90, 568 to 10 days89, 655 after
the initial symptoms. Since a steep increase in the number of complications occurs if the operation is performed later than 10 days after the initial symptoms89, 655, operation is recommended to be performed not later
than 7-10 days after symptoms started. If this is not possible, the patient
should be discharged and operated electively approximately 3 months
after the initial symptoms552.
Access for cholecystectomy for acute cholecystitis
Cholecystectomy for acute cholecystitis can be performed by traditional
open laparotomy, minilaparotomy and laparoscopy. When laparoscopic
cholecystectomy was introduced, acute cholecystitis was a relative contraindication, but the indication area was gradually expanded to include
this condition too89, 233. Both the conversion rate to open cholecystectomy
and the number of complications are higher for operations for acute
cholecystitis than for elective cholecystectomy418. The rate for conversion
to open surgery depends on the degree of cholecystitis and duration of the
symptoms160, 210, 265, 347.
No studies exist that compare laparoscopic cholecystectomy for acute
cholecystitis with cholecystectomy by minilaparotomy or traditional open
laparotomy. A single study compares cholecystectomy by traditional open
laparotomy with minilaparotomy. There were 30 patients in each group51.
The duration of the operation, the technical difficulties and complications
were identical in the two groups. Minilaparotomy lead to lower consumption of analgesics, less time spent in hospital (3.1 day vs. 4.7 days)
and quicker resumption of normal activities compared to traditional open
laparotomy (73% vs. 40% after 2 weeks). The survey was not blinded.
96
Preoperative treatment
It has been discussed, to what extent the gallbladder should be drained as
a matter of routine in patients with acute cholecystitis. A single randomised survey673 showed that patients drained by ultrasound were free
of fever and pain, could eat and were discharged from hospital significantly faster than those who only received systemic antibiotics. However,
no randomised surveys have been conducted to study the extent to which
drainage with subsequent cholecystectomy is a better solution than a subacute cholecystectomy without drainage. Thus, the extent to which
drainage is necessary if a decision to operate has been taken anyway is
open to question. In certain – more complicated – cases it could be an advantage to bring the patient in optimal health before an operation, but the
literature does not provide proper evidence in favour of this. Since preoperative drainage is used in many hospitals, a more in-depth study of this
technology is needed.
In one randomised double-blind study, preoperative treatment of patients with acute cholecystitis with non-steroid anti-inflammatory drugs
led to a significant reduction of temperature and pains compared with the
placebo group. In those who were not operated, it also reduced the length
of the stay in hospital781. This corresponds to two other randomised trials,
in which patients who were admitted acutely with gallstone pains, were
randomised for non-steroid anti-inflammatory drugs or placebo18, 283.
In both cases, progression to acute cholecystitis was significantly lower in
the group that was treated. Non-steroid anti-inflammatory drugs reduce
the pressure in the gallbladder during acute cholecystitis780, a further sign
that the drugs impede or delay the development of acute cholecystitis.
Time spent in hospital, sick leave and complications
There are too few larger consecutive series (>200 patients) of newer date
to give an impression of the time spent in hospital, duration of sick leave
and the complication rates for the different methods of cholecystectomy90,
638, 655, 796, 809
. Furthermore, the materials differ a lot due to the broad clinical spectrum of acute cholecystitis. The single randomised comparison
of traditional open laparotomy and minilaparotomy51 suggested that
patients with uncomplicated acute cholecystitis spend more or less the
same amount of time in hospital and convalescing as patients with an elective cholecystectomy.
Lesion of the bile ducts is 2-3 times more common after operations on
patients with acute cholecystitis than after elective simple cholecystec-
97
tomy. There are no signs that this over-frequency of bile duct lesions has
diminished since the introduction of laparoscopic cholecystectomy658.
Mortality
The 30-day mortality rate for simple cholecystectomy after acute cholecystitis shows a number of fluctuations throughout the period studied
(figure 37). If the patients’ general health is included, the mortality rate is
significantly higher in the last three sub-periods compared with the first
one (table 10). The 30-day mortality rate has also tended to rise over the
years. Introduction of laparoscopic cholecystectomy has not reduced mortality after acute cholecystitis. By comparing the higher mortality rate after cholecystectomy for acute cholecystitis with elective cholecystectomy,
a rise can be detected over the years (1978-83: OR=1.25 (95% c.l. 0.931.67); 1984-87: OR=1.44 (95% c.l. 1.07-1.94); 1988-91: OR=1.85 (95%
c.l. 1.29-2.65); 1992-95: OR=2.62 (95% c.l. 1,72-3,98)). One has to
make certain reservations in regard to the data for the final sub-period because patients with acute cholecystitis were not always classified correctly
in 1994-95 (page 93). It is impossible to make comparisons with the available literature, since no valid recent studies exist of 30-days mortality
rates after cholecystectomy for acute cholecystitis.
6.3.2 Cholecystolithotomy and partial cholecystectomy
Cholecystolithotomy and partial cholecystectomy are well-known technologies, if the anatomical circumstances are such that the gallbladder
cannot be removed without grave risk of lesion to the bile duct 704. Cholecystolithotomy is also used for particularly sick patients, as it can be performed under a local anasthesia118. A number of series have been published which show that this technology is used to a certain extent297, 381, 850,
but no comparable studies have been made.
6.3.3 Ultrasonic drainage
Drainage of acute cholecystitis was not a readily available option until the
introduction of ultrasound. The first description is of ultrasonic drainage
of an empyema (an abscess in the gallbladder)623. A number of series have
been published112, 339, 499, 804, 808 showing that the technology can be used,
and that it is used in Denmark735. The greatest problem is the risk of the
drain sliding out of position and causing a leak of bile into the abdominal
cavity. As with elective conditions (page 85), ultrasonic drainage can be
followed by dilation of the canal, pulverisation (laser/ultrasound) of the
98
gallstones and subsequent flushing out of the remains of stones345. Because
of the low mortality rate (0.4%)773 after percutaneous cholecystotomy,
this treatment is recommended6 for patients who are too sick to undergo
an operation. Literature about larger clinical series and especially about
following-up on these patients is scarce.
Discussion
A number of technologies exist to relieve acute infection of the gallbladder. However, the literature is incredibly weak, since nobody has conducted comparable studies to find out which treatment is best under
which circumstances. Acute infection of the gall bladder stretches from
a reasonably straightforward condition – which can be dealt with by a
cholecystectomy without causing greater problems than elective cholecystectomy – to acute life-threatening conditions. Furthermore, the patients’
conditions vary from no co-morbidity to a high degree of co-morbidity.
The literature provides no evidence of when cholecystectomy ought to be
performed, when drainage ought to be used and followed up with a cholecystectomy, or when drainage alone is sufficient. In the absence of clearcut recommendations, many departments have devised their own methods
of solving the problem.
6.3.4 Acalculous cholecystitis
Patients with acalculous cholecystitis make up a special sub-group who do
not have stones in the gallbladder and who are often very sick for other
reasons. The majority of cases arise after major traumas and major operations. The acute treatment consists of drainage of the gallbladder. The
question is: to what extent this treatment ought to be followed up with
a cholecystectomy during a calm phase? In a single series covering 19
patients who were followed for a median 26 months, 17 remained free of
symptoms and had properly functioning gallbladders78. There are no comparable studies.
99
7. Treatment of patients with
choledochal stones
The vast majority of stones in the bile ducts stem from the gallbladder and
can be seen as a complication to gallbladder stones (see section 1.1.3).
Stones generated primarily in the bile ducts are usually formed during infections.
7.1
D EVELOPMENTS IN D ENMARK , 1978-95
Courses of treatment that include bile duct treatment as part of the index
treatment make up 27% of the total number (table 1). Slightly over half
of the patients also had a cholecystectomy. The vast majority of the patients (94.4%) had stones in the bile ducts, while the rest had benign tumours and biliary tract dyskinesia. Among the latter there was a rise from
4.5% in 1978-83 to 7.4% in 1992-95.
The survey of bile duct treatment from 1978-95 was based on patients
who had open or endoscopic treatment for bile duct disorders independent of simultaneous cholecystectomy (figure 41).
FIGURE 41
All operations on bile duct - with biliary tract diagnosis
Rate per 100,000
40
35
30
25
20
15
10
5
0
Year 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95
Women
100
Men
The rate for women fell by 30% from 1978 to 1991 (2.3% per annum)
and rose by 22% until 1995 (5.6% per annum). The rate for men fell 13%
from 1978 to 1991 (1.0% per annum) and rose by 31% until 1995 (7.7%
per annum).
The curves indicate a number of characteristic changes in the pattern
of treatment. The most prominent is a fall in the rate of traditional open
bile duct surgery (figure 42) and a rise in the rate of endoscopic bile duct
treatment (figure 43).
FIGURE 42
Open bile duct surgery - with biliary tract diagnosis
Rate per 100,000
35
30
25
20
15
10
5
0
Year 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95
Women
Men
The declining rate of open bile duct surgery was due in particular to a
noticeable reduction in the proportion of patients who had an open cholecystectomy simultaneous with bile duct surgery, while the increase in endoscopic bile duct treatment was predominantly due to the use of endoscopic sphincterotomy as the only treatment. A total picture of developments in the different types of bile duct treatment is included in appendix 3.
101
FIGURE 43
Endoscopic bile duct surgery - with biliary tract diagnosis
Rate per 100,000
35
30
25
20
15
10
5
0
Year 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95
Kvinder
Mænd
The age-related rates (figure 44 & 45) show that bile duct treatment is
most prevalent among the elderly. The treatment rate reaches a minor
peak for 30-year-old women.
FIGURE 44
All operations on bile ducts - women, with biliary tract diagnosis
Rate per 100,000
180
160
140
120
100
80
60
40
20
0
Age 0
10
1978-1983
102
20
30
1984-1987
40
50
1988-1991
60
70
1992-1995
80
FIGURE 45
All operations on bile ducts - men, with biliary tract diagnosis
Rate per 100,000
180
160
140
120
100
80
60
40
20
0
Age 0
10
1978-1983
20
30
1984-1987
40
50
1988-1991
60
70
80
1992-1995
Discussion
The switch from open to endoscopic treatment corresponds to international developments232. The fall in the number of operations on the bile
ducts in the 80s also corresponds to the literature605. No international
studies were found that describe possible changing operation rates on the
bile duct since the introduction of laparoscopic cholecystectomy.
The decrease in the number of operations on the bile ducts in the 80s
may be due to the decrease in incidence of gallstones. Another explanation may be that attitudes to examining patients with stones in the gallbladder changed from routine examination for stones in the bile ducts in
all patients who had a cholecystectomy, to examining only selected patients who displayed signs of stones in the bile ducts21, 311. The reason for
this change in attitudes was that the routine examination gave occasion to
unnecessary operations on the bile ducts, partly because of a number of
false positive findings and partly because of findings of small gallstones, a
large number of which would have passed spontaneously311, 543. After the
introduction of laparoscopic cholecystectomy, reintroduction of routine
intraoperative cholangiography or preoperative ERCP was advocated by
some77, 113, 662. This may have increase the rates of unnecessary ERCP and
intraoperative cholangiography and associated treatments. Since endo-
103
scopic and open treatment of bile ducts are associated with few, but serious complications, it is important to draw up appropriate guidelines for
diagnostics of stones in the bile ducts.
Conclusion
While the number of open operations on bile ducts (with or without cholecystectomy) fell throughout the whole period – coinciding with the spread
of ERCP – the rate of endoscopic bile duct surgery rose. The pattern in
these changes was expected. While the total number of patients who had
bile duct treatment fell in the 80s, the number rose after the introduction
of laparoscopic cholecystectomy.
7.2
I NDICATION FOR EXAMINATION AND TREATMENT OF STONES IN THE BILE DUCTS
Stones in the bile ducts are diagnosed either because of symptoms (jaundice, infection of the bile ducts, pains and pancreatitis) or by a routine survey of the bile ducts during cholecystectomy. In the case of symptoms,
there is always an indication for treatment, while routine examination and
treatment of randomly discovered stones can be discussed. Many of the
stones in the bile ducts probably pass spontaneously448. The question is:
what is the best strategy for examining a patient for stones in the bile ducts
in connection with a cholecystectomy?
Examination of the bile ducts in connection with cholecystectomy can
be intraoperative cholangiography, ERCP or MRC. Only ERCP has a
treatment code in the National Hospital Discharge Register, while the
other two are not registered (there would, however, not be many with
MRC before 1995). The proportion of simple cholecystectomy patients
who undergo diagnostic ERCP is illustrated in figure 46. The curve shows
a clearly rising tendency - especially after the introduction of laparoscopic
cholecystectomy. To what extent the rise is exclusively due to ERCP replacing intraoperative cholangiography or reflects changes of the indications cannot be assessed.
104
FIGURE 46
ERCP during hospitalisation for simple cholecystectomy
Percent
10
9
8
7
6
5
4
3
2
1
0
Year 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95
A lot of articles mention the lack of agreement about which patients
should be examined for bile duct stones in connection with an impending
cholecystectomy. A systematic study of the literature - involving both observational studies and randomised surveys – does provide a clear picture,
however:
❖
Patients shown by ultrasound not to have a broad bile duct (>6-10 mm), patients
who do not have jaundice or liveraffection, do not have a broad ductus cysticus,
do not have a pancreatitis and do not have palpable stones in ductus choledochus intraoperatively, very rarely have bile duct stones 1, 178, 310, 761, 857. These findings
suggest that not all cholecystectomy patients need to be examined for stones in
the bile ducts.
❖
The consequence of conducting intraoperative cholangiography on all patients
are a number of false positive findings and consequent unnecessary choledochal
exploration 857.
❖
Follow-up of groups of patients, whose bile ducts were not examined in connection with cholecystectomy, revealed no 292 patients or only one single patient with
choledochal stones 293.
❖
Patients with no signs of bile duct stones were randomised for intraoperative cholangiography or not 311, 543, 723. In the control group, no patients had residual stones in
ductus choledochus - not even after 6-8 years follow-up 309. In one of the studies 543,
105
12% of those who had intraoperative cholangiography had choledochus stones.
Thus a number of unnecessary operations was the consequence of routine examination for choledochal stones.
❖
Comparison of routine intraoperative cholangiography with selective intraoperative cholangiography showed - in randomised trials - that the latter strategy was
justifiable 21, 706.
Thus, simple techniques make it possible to identify approx. 80%769 of the
patients who do not need a closer examination of the bile ducts in connection with a cholecystectomy. However, surgeons do not always adhere
to these simple rules. A questionnaire survey in the USA showed that approximately half of the surgeons recommended routine intraoperative
cholangiography111.
Comparison of diagnostic methods
The comparison between MRC and ERCP attracts special interest, as the
former method is non-invasive and, therefore, not associated with the
complications caused by ERCP. The method is promising727 but would be
expensive, if new equipment had to be purchased exclusively to examine
biliary tracts. In recent years, it has been proven that intraoperative ultrasound scanning is excellent for routine identification of stones in the bile
ducts66, 652 but the examination ought not to be performed unless indications are clear.
Conclusion
Without reducing the safety and quality of the treatment, the proportion
of operations on the bile ducts could be reduced significantly by introducing fixed guidelines for examinations for stones in the bile ducts in patients due to undergo a cholecystectomy. The new MRC technology needs
to be assessed in relation to ERCP but should not entail changes to the actual indication for examination of the bile ducts.
7.3
M ETHODS OF TREATMENT
The primary purpose of the treatment is to provide a drain for the bile,
while the secondary purpose is to remove gallstones. For this section, a
systematic literature search has been conducted in order to identify all randomised trials . The technologies described are:
❖
106
surgical removal (traditional open bile duct surgery, bile duct surgery by minilaparotomy and laparoscopic bile duct surgery)
❖
endoscopic removal (via ERCP or percutaneous methods).
7.3.1 Surgical methods of treatment
Only a few recent (post-1978) clinical series covering more than 200 patients have dealt with traditional open choledochal surgery 237, 561, 580. They
all reveal good results for removal of the stones in 96-98% of the cases.
Correspondingly, only two studies of more than 200 patients were identified in which laparoscopic choledochal surgery was consistently used on
bile duct stones76, 523 with a success rate of 96-97%. Laparoscopic choledochal surgery has not been as widespread as laparoscopic cholecystectomy and has not yet been introduced in Denmark37. Choledochal surgery
by minilaparotomy is mentioned only casuistically197, 532.
Complications – mainly in the form of sepsis, biliary leak, pneumonia
and haemorrhaging – were calculated either very differently or not at all,
so it has not been possible on the basis of such sparse material to compare
the three methods. No randomised surveys have been conducted that
compare the three methods. Several sources stress that the laparoscopic
approach is still at the experimental stage37.
7.3.2 Endoscopic methods of treatment
A number of clinical series have been published that deal with endoscopic
treatment of stones in the bile ducts. A study of series of 200+ consecutive
patients treated after 1978 reveals that the technology has the same success rate as open surgery as far as removal of stones is concerned - varying from 82% to 97%52, 85, 851. The complications are different than in the
case of open surgery and mainly consist of haemorrhaging, pancreatitis,
infection of the bile ducts and perforation of the duodenum - varying from
5% to 14%. The most serious complication, perforation of the duodenum, was seen in 0.1%-3%74, 85, 97, 131, 136, 154, 238, 248, 442, 459, 707, 708, 800, 843, 851.
The extent to which endoscopic operation for stones in normally calibrated bile ducts causes more complications than operations in dilated
bile ducts has been discussed and conflicting results emerge from the literature136, 843. On the other hand, it is generally agreed that endoscopic
treatment of a slender bile duct without stones (e.g. for sphincter Oddi
dyskinesia - page 83) is associated with a two-fivefold increased risk of
complications compared with a stone-filled bile duct248, 708. There is considerable disagreement about the extent to which prophylactic antibiotic
treatment should be administered to patients suspected of having stones
107
in the bile ducts in order to avoid subsequent infection. One randomised
survey shows a positive effect122 while two others failed to concur 229, 314.
The 30-day mortality rate was calculated at 1.2%-4.7% 248, 459, 708, 800.
Alternative or supplementary technologies along with endoscopic treatment
In order to avoid complications associated with sphincterotomy, a method
has been developed whereby the bile duct sphincter is dilated with a balloon before the bile duct stones are removed474. In addition, a number of
technologies have been developed to deal with the more complicated
choledochus stones that cannot be removed by general sphincterotomy or
balloon dilatation:
❖
Application of stent (plastic tube so bile can pass the stones) 125, 397, 741.
❖
Contact pulverisation (laser) through a so-called mother-child scope (thin scope is
passed through the normal-size scope up into the bile duct) 156, 563, through a drainage tract (after an operation) 617 or transheptically 342, 753.
❖
Mechanical pulverisation 142, 710 by ERCP or drainage tract.
❖
Dissolution of the stones by injecting ether or other solvents 544, 559, 751, 786 into the bile
duct;
❖
ESWL (extracorporeal contusion) 7, 517, 738.
These technologies have rarely been compared in clinical series. One randomised survey showed that balloon angioplasty was just as good as
sphincterotomy 81, while another randomised survey showed that
lithotripsy (contusion of the stones via ERCP) was better than ESWL because fewer courses of treatment and examinations were necessary348.
Subsequent cholecystectomy
Should patients subsequently have their gallbladders removed after successful endoscopic treatment of bile duct stones? A number of clinical series show a cholecystectomy rate of 6-20% in a follow-up of 3-4 years 191,
302, 305, 326, 344, 415, 558, 763
. The vast majority of the cholecystectomies were performed within 1-2 years302, 326. The majority of the indications for subsequent cholecystectomy consisted of acute cholecystitis that was treated
without any problems.
It can be concluded that subsequent cholecystectomy is not justified
unless the patient develops symptoms that can be ascribed to stones in the
gallbladder.
108
7.3.3 Comparison between surgical and endoscopic treatment
Surgical treatment has been compared with endoscopic treatment in a
number of randomised trials:
❖
In four of these trials (230 patients), the patients were randomised to preoperative
endoscopic removal of stones in the bile duct followed by traditional open cholecystectomy or cholecystectomy and removal of bile duct stone by traditional open
laparotomy 394, 557, 737, 748. An overall evaluation of the complication rates, mortality
rates and direct costs, revealed that using the endoscopic method as opposed to
open surgery did not offer any advantages.
❖
Three studies representing 263 patients 303, 424, 764 compared endoscopic treatment
(with no immediate plan for a subsequent cholecystectomy) with open surgery.
One of the studies, which covered patients with acute infection of the bile ducts 424,
showed significantly lower mortality rates for acute endoscopy compared with
acute open surgery, while the other two 303, 764 both suggest surgery as the initial treatment.
❖
One single randomised trial 167 representing 207 patients found that preoperative
endoscopic treatment and subsequent laparoscopic cholecystectomy are no better than a laparoscopic operation that removes both gallbladder and bile duct
stones, as the total time spent in hospital by the endoscopic group was 9.5 days
compared to 6.5 days for the laparoscopic group.
Conclusion
Endoscopic treatment of stones in the bile ducts is probably best suited to
acute infection of the bile ducts but otherwise does not appear to be any
better than either open surgery or laparoscopic surgery. The source material is, however, small and varied in nature, so it is difficult to draw definitive conclusions. A major randomised survey of endoscopic vs. open
treatment is needed. It might be worth considering whether the open treatment should follow the principles as minilaparotomy.
7.3.4 Thirty-day mortality rates in Denmark, 1978-95
As endoscopic bile duct treatment is presumed to cause less surgical
trauma than corresponding open surgery, a fall was expected in the 30day mortality rate after treatment for stones in the bile ducts during the
period studied because the proportion of endoscopic bile duct treatments
increased. The mortality rate decreased throughout the period for patients
admitted electively but there is no clear tendency for acute admissions (figure 47). The 30-day mortality rate (table 12) also decreased in the analy-
109
sis that took account of age, gender and co-morbidity. The decrease was
most pronounced among elective patients.
TABLE 12
The 30-day mortality a in all patients who had operations on biliary ducts in relation to the
method of admission and period. Only cases with biliary tract diagnoses were included and in
the multiple logistic regression analysis account was taken of age, gender and co-morbidity.
All operations on the bile ducts
Period
Elective admission
Acute admission
Total
OR (95% c.l.)
OR (95% c.l.)
OR (95% c.l.)
1978-1983
1.00
1.00
1.00
1984-1987
0.59 (0.36-0.97)
0.95 (0.73-1.23)
0.84 (0.67-1.05)
1988-1991
0.54 (0.31-0.95)
1.11 (0.86-1.44)
0.95 (0.76-1.19)
1992-1995
0.59 (0.33-1.04)
0.85 (0.64-1.11)
0.76 (0.60-0.97)
a: The mortality is measured from the date of admission as the actual date of operation is not stipulated in the National Hospital
Discharge Register
FIGURE 47
All operations on bile ducts - mortality rates standardised for gender and age
Number per 1,000
70
60
50
40
30
20
10
0
Year 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95
Total
Acute
Elective
The literature contains insufficient information about the 30-day mortality rate after operation on bile duct
110
8. Treatment of patients with
gallstone pancreatitis
Gallstone pancreatitis is probably caused by an acute obstruction at the
confluence of the choledochal and pancreatic duct either because of a
stone blocking the passage or because of the oedema that occurs when a
stone is passed4, 576.
Cases of gallstone pancreatitis are classified as mild or severe in accordance with recognised guidelines – the Glasgow criteria95 or the Ranson
criteria632. In mild cases, pancreatitis passes quickly, while severe cases
may cause necrosis of the pancreas and abscesses and develop into a lifethreatening condition.
8.1
D EVELOPMENT IN D ENMARK , 1978-95
No separate curves have been drawn up for treatment of patients with
gallstone pancreatitis, since the patient category cannot be identified with
100% accuracy in the National Hospital Discharge Register. Treatment
form part of the curves for simple cholecystectomy and for treatment of
stones in the bile ducts.
8.2
I NDICATION FOR TREATMENT
As a general principle, there is always an indication for treatment when a
patient is diagnosed as having gallstone pancreatitis as the risk of recurrence is 25-50%211, 495, 586.
8.3
M ETHODS OF TREATMENT
The primary purpose of the treatment is to make sure that the pancreatitis does not develop into a serious condition. The secondary purpose is to
remove the cause of the pancreatitis, so the patient does not suffer a relapse.
The technologies used are:
❖
Cholecystectomy (in the form of traditional open laparotomy, minilaparotomy or
laparoscopy) perhaps combined with open or endoscopic bile duct treatment.
❖
Endoscopic operation (ERCP with sphincterotomy) perhaps followed by simple
cholecystectomy.
111
8.3.1 Cholecystectomy
Until the late 70s, the standard treatment was traditional open cholecystectomy combined with choledochal surgery if stones were found intraoperatively.
Timing of cholecystectomy in relation to pancreatitis
Because of the high risk of relapse, it was suggested as early as 1964 that
cholecystectomy should be performed during the same stay in hospital
when the pancreatitis had subsided instead of waiting for a subsequent admission277. A randomised trial755 supported this treatment policy, as it
showed that patients operated during the same stay in hospital were ill for
a shorter period of time than those operated six weeks later. There was no
difference in the complication rates for the two groups. However, the
study is not up-to-date, since open sphincterotomy was consistently performed on all – an operation only extremely rarely carried out these days.
A corresponding randomised survey is mentioned in the literature but
does not appear to have been published473. The principle of treatment during the same stay in hospital has evidently worked well according to a
whole string of clinical series – summed up in a review article593.
One suggestion in favour of sub-acute operation within 48 hours5 was
contradicted by others389, 632. A randomised trial390, in which 165 patients
were allocated to either early (<2 days) or late (4-10 days after admission)
cholecystectomy, showed that there was no significant difference between
the two treatment strategies in the group with mild pancreatitis. The
group with severe pancreatitis did, however, suffer a significantly greater
number of complications and deaths using the early strategy than it did
using the later strategy.
Cholecystectomy by traditional open laparotomy, minilaparotomy or
laparoscopy
After the laparoscopic method was introduced, it gradually became common for cholecystectomy after acute pancreatitis177. A survey of all cholecystectomies in the state of Connecticut in the USA658 from 1989 to 1993
showed that the occurrence of bile duct lesions in cholecystectomy for
acute pancreatitis was significantly higher than for elective cholecystectomies and that the complications seem to be greater for laparoscopic
technology than for traditional open technology. No series analysed the
30-day mortality rate. No randomised surveys exist that compare the
three methods of cholecystectomy.
112
8.3.2 Endoscopic treatment
Endoscopic sphincterotomy for acute gallstone pancreatitis was not described until the late 70s and early 80s144, 668, 731. The philosophy behind
this technology is to provide a drain for the bile duct early to make the
pancreatitis subside. A whole string of clinical series show that this technology can be used – summed up in a review845.
Acute endoscopy versus ‘wait-and-see’ attitude
Four randomised trials have been identified216, 235, 556, 560, 570 covering 742
patients. In each of these surveys, the patients were randomised either to
sub-acute endoscopy with sphincterotomy (if the examination revealed
stones in the bile duct) or expectant treatment supplemented with later endoscopy if the clinical situation necessitated it. The effect was measured in
terms of the length of admission, complications and mortality rates. It was
generally agreed that patients with mild gallstone pancreatitis do not benefit from early endoscopy and sphincterotomy – there may even be an increased risk of complications in the group who undergo endoscopy
early216. As far as patients with a severe pancreatitis are concerned, the results diverge from a distinct positive effect of early endoscopy556, 570 to a
distinct tendency216 towards a negative effect because of too many severe
complications235. All the works can be criticised on one or more points, including the way they delineate the patient population.
It should be noted that the earlier patients with gallstone pancreatitis
have their bile duct examined, the greater the probability of finding the
stone(s) before it/they pass spontaneously. In patients examined within
two days of initial symptoms, stones were found in the bile ducts in 4470% of cases, while in patients examined 3-7 days after the initial symptoms, stones were found in the bile ducts in 20% of cases865, 866.
8.3.3 Treatment strategies for gallstone pancreatitis – summary
Treatment within 48 hours
In the acute phase, no indication was found for specific treatment of mild
gallstone pancreatitis. A single randomised survey showed that acute
cholecystectomy ought not to be performed for severe gallstone pancreatitis390, while four randomised examinations failed to give a straightforward picture of the extent to which a sphincterotomy should be performed216, 235, 556, 560, 570.
113
Treatment before discharge
Both cholecystectomy and endoscopic sphincterotomy seem to prevent recurrence of pancreatitis, so it is recommended that all patients with gallstone pancreatitis have performed one of these treatments before discharge. However, there is a shortage of randomised surveys to prove
which treatment is best. It is suggested494 that at least those patients who
have difficulty coping with an operation should have a sphincterotomy after the pancreatitis has been dealt with successfully (regardless of whether
there are stones in the bile duct or not).
Treatment after discharge
Should patients who have had a sphincterotomy subsequently undergo a
cholecystectomy? A single work was identified covering 51 patients830 in
which the patients were followed after sphincterotomy without a subsequent cholecystectomy. A total of two developed new cases of pancreatitis in a follow-up period of 27 months. Both cases occurred in a group of
three patients for whom the initial sphincterotomy was stipulated as being insufficient. No information was provided about other complications
associated with the fact that the gallbladder was not removed.
Conclusion
As a main rule, patients with gallstone pancreatitis should undergo final
treatment (cholecystectomy or sphincterotomy) before discharge. It is not
known which method is best. General agreement has not been reached
about the initial treatment of severe gallstone pancreatitis. Further research is needed in the area. Patients who undergo sphincterotomy do not
need a subsequent routine cholecystectomy.
114
9. The patient
A number of the factors normally covered in the chapter about the patient
have been included in the technology section of this assessment. This approach was chosen because it seemed the most natural. The topics concerned were postoperative pains, length of hospitalisation, convalescence
and persistent pains.
9.1
T HE PATIENT ’ S CHOICE OF TREATMENT PROCEDURE
Literature is particularly sparse in this area. Even though many articles
about laparoscopic cholecystectomy start off by stating that laparoscopic
cholecystectomy has now become a patient demand, the evidence for this
is very scarce. A single work has been identified in which the patient’s view
of different gallstone treatments has been investigated by means of an interview survey68. Forty patients were selected with various medical illnesses but not with gallstones. Patients without gallstones were chosen because they are assumed not to be prejudiced. A panel consisting of clinical
experts in gallstone treatment (two surgeons, a gastroenterologist, a radiologist and a nurse), three health service researchers and a lay person,
drew up descriptions of traditional open cholecystectomy, laparoscopic
cholecystectomy and ESWL as well as of possible temporary consequences
(acute cholecystitis, gallstone pancreatitis, postoperative sepsis , post-operative bile duct stones and post-operative bile duct stricture) as well as of
chronic results (post-cholecystectomy pains, biliary colic, persistent
asymptomatic gallstones and surgical scars). The preference for each
treatment and result was to be stated on a scale from 0 (death) to 100 (perfect health). ESWL was deemed slightly better than laparoscopic cholecystectomy and both of these technologies were deemed preferable to traditional open cholecystectomy. The preferences were far from definitive
and depended on the possible temporary and chronic consequences. For
both post-cholecystectomy pains and biliary colic, the preferences depended on the regularity of the symptoms – the more often, the lower the
preference. The preferences were not dependent on gender, age and race.
The article does not divulge the nature of the detailed descriptions of the
individual procedures. Thus, it does not reveal what information was provided about the difference between, for example, serious complications.
115
Cholecystectomy by minilaparotomy and “watchful waiting” were not included in the assessment. It was impossible to identify works that analyse
gallstone patients’ preferences for the different methods after they have
been provided with detailed information.
Knowledge of patient preferences ought to be expanded. Bass’ method
68 could be adapted to include a greater number of aspects and used with
a group of patients due for gallstone treatment. This would require a department that masters all the different potential forms of treatment.
9.2
P ATIENT EXPECTATIONS
A single work dealt with patient expectations of gallstone treatments649.
All the patients expected to be cured of their pains as well as of any complications to their gallstone disorders and 86% of the patients with dyspeptic symptoms expected to be cured of these too – either because the patients thought that the symptoms were connected with their gallstone disorders or because their doctor had said they were
9.3
P ATIENT INFORMATION
According to the Danish National Board of Health38, the patient has the
right to be informed about his health and about treatment options, including the risk of complications and side effects. Health service employees are also obliged to inform patients of serious and common complications at all times and to inform them of serious and rare complications in
most cases. Information about complications has to be weighed in relation
to the seriousness of the disease and the expected effect of a given treatment. Thus, staff can weigh the information about the possible treatments
including advantages and disadvantages. No studies exist about the extent
to which patients are informed about the risk of complications and what
influence this has on the patients’ choice of procedure.
Few studies abroad have looked at the patients’ assessment of the information provided. A total of 77% considered the information provided
before a cholecystectomy to be sufficient92. In another study, the patients
found that they received adequate information about the necessity of their
operation378, although the percentage was slightly higher for laparoscopic
cholecystectomy (96%) than for traditional open cholecystectomy (94%).
This high degree of satisfaction with general questions is well-known from
other patient satisfaction surveys. When posing more specific questions, a
different assessment is often seen. In a detailed postoperative study of laparoscopic cholecystectomy (the patients were interviewed on days 1, 2,
116
3, 4 and 7 after the operation), the majority of patients stated that they
were suffering from greater pain, more nausea, vomiting and fatigue than
they had been led to expect by the information provided in advance of the
operation130.
9.4
T HE PATIENT ’ S ASSESSMENT OF THE GIVEN TREATMENT
Assessment of persistent pains has been thoroughly discussed earlier (section 5.2 & table 3 in appendix 3). This section will, therefore, focus on
other ways of measuring levels of satisfaction.
Complete or partial success/satisfaction was claimed after 86-94% of
laparoscopic and 82-95% of traditional open cholecystectomies378, 846. In
a multi-centre study involving eight European countries, 91% said that
the result of their laparoscopic cholecystectomy was as expected and 79%
said that they recovered as quickly as they had expected92. No special age
difference was experienced as far as general satisfaction with the given
treatment was concerned (84% in patients over 60 year and 79% among
the rest)531. A series of quality targets concerning pre-operative expectations, choice of the same operation again, satisfaction with the stay in hospital plus time spent with the doctor(s) and nurse(s) varied from 88-97%
– all with a tendency to slightly poorer results in those who had traditional
open cholecystectomy than in those who had laparoscopic cholecystectomy. This could be interpreted as greater interest in the latter patient category378. A large proportion (26% and 23% after traditional and laparoscopic cholecystectomy, respectively) thought that they were sent home
from the hospital too soon (4 days and 1 day after the operation, respectively).
Comparison between cholecystectomy by minilaparotomy and by laparoscopy in a blinded study showed that an equally large share of patients in the two groups considered the result excellent or good after 1 and
12 weeks504. There was a tendency for the laparoscopy group to be more
satisfied than the minilaparotomy group, but after a year505 there was no
difference in the success rates (table 13). A significantly larger number of
the laparoscopy group were satisfied with their scar after 12 weeks (84%)
compared with the minilaparotomy group (74%). While 97% of patients
in the laparoscopy group said they would have chosen the same operation
again, the corresponding figure for the minilaparotomy group was
94%504. In other words, the all-round level of satisfaction was very high
indeed.
117
TABLE 13
Patients’ general satisfaction with the result of cholecystectomy by laparoscopic method or
minilaparotomy.
Method of access
Satisfaction at different times after the operation
Laparoscopic
Minilaparotomy
One week after the operation
Excellent
60%
41%
Good
26%
45%
Satisfactory or poor a
14%
14%
12 weeks after the operation
Excellent
69%
54%
Good
23%
39%
8%
7%
Excellent
59%
58%
Good
25%
21%
Satisfactory
11%
14%
5%
7%
Satisfactory or poor a
1 year after the operation
Poor
a: The author does not differentiate between “satisfactory” and “poor” in the surveys after 1 and 12 weeks. McMahon 504, 505
Two of the randomised surveys comparing cholecystectomy with ESWL
showed equally satisfactory quality of life measured by two different questionnaires64 and by the Nottingham Health Profile565, while the third revealed significantly higher quality of life after traditional open cholecystectomy than after ESW 615.
Discussion
In general, patients are highly satisfied with the biliary tract treatment
they have received. Just after the treatment, there is a tendency towards
greater satisfaction among those who undergo laparoscopic cholecystectomy and ESWL compared to the open forms of operation where patients
can be affected by staff attitudes to the new forms of treatment. After a
year, there was no difference in assessments of the treatments. Many felt
they were discharged from hospital too quickly.
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10. Organisation
10.1 A DMINISTRATIVE RULES FOR THE TREATMENT OF PATIENTS WITH GALLSTONES IN
D ENMARK
According to the National Board of Health’s ‘Special planning and national and regional functions in the hospital service’36, cholecystectomy
with associated uncomplicated open bile duct surgery is a basic treatment.
Thus, in principle, it has to be available in every surgical department that
provides a basic service. The guidelines stipulate that ERCP should be
concentrated at one central location in each county, since at least 100 examinations must be conducted per annum. The treatment of severe choledochus stones, bile duct stricture and bile duct lesions is, however, a national/regional function and should be concentrated in four specific departments around the country. Examinations for, and treatment of, biliary
tract dyskinesia should be available in two specific departments in the
country.
Due partly to regional variations in the services on offer, the Danish
National Board of Health set up a working party to recommend ways of
drawing up definitive indications for specific treatments. In 1995, the
working party recommended33 that efforts in the area be intensified – e.g.
by drafting reference programmes and holding consensus conferences. As
far as gallstone treatment is concerned, these recommendations were not
followed up, although this HTA report could be considered part of the
process.
10.2 G ALLSTONE TREATMENTS IN D ENMARK
10.2.1 Developments in Denmark, 1978-95
In 1978-83, 75 surgical departments performed biliary tract surgery in
Denmark, falling to 58 in. If all biliary tract operations were taken together, an average of 81 operations were performed per department per
annum in 1992-95, varying from 10 to over 100 per annum. A total of 5
departments performed less than 25 operations per annum, while 14 departments performed more than 100. As far as simple cholecystectomy
was concerned, an average of 55 operations were performed per department per annum in 1992-95, varying from under 10 to over 100 operations per annum. A total of 9 departments performed less than 25 chole-
119
cystectomies per annum, while 6 conducted more than 100 per annum.
No figures are available for the number of doctors performing gallstone
operations in Denmark during the period in question. If the average number of surgeons performing biliary tract surgery per department was four,
the average number of simple cholecystectomies per surgeon would have
been approximately one per month.
10.2.2 Morbidity and mortality in relation to the number of operations
The surgical departments were divided into four equally large groups
(quartiles) based on the number of cholecystectomies performed per annum (appendix 4). The proportion of simple cholecystectomies after
which the patient was readmitted for new biliary tract procedures was significantly higher in the hospitals that performed the fewest operations.
The material does not reveal the extent to which the re-admissions were
due to residual choledochal stones or bile duct lesions (table 14). On the
other hand, there was a tendency for the 30-day mortality rate to be highest in those hospitals, in which the greatest number of gallstone patients
were treated per annum (table 14). This report is unable to explain the differences found.
TABLE 14
Morbidity and 30-day mortality after simple cholecystectomy in relation to the number of
surgical procedures per annum.
Morbidity
Mortality
Quartiles
OR (95% c.l.)
OR (95% c.l.)
1st quartile a
1,45 (1,02-2,07)
0,94 (0,67-1,34)
2nd quartile
1,11 (0,86-1,43)
0,78 (0,62-0,99)
3rd quartile
0,93 (0,74-1,17)
0,85 (0,71-1,03)
4th quartile
1,00
1,00
a: The departments were divided up into four equal parts based on the number of simple cholecystectomies performed per annum.
The first quartile represents the quarter of the departments that perform the fewest operations.
10.3 T RAINING FOR GALLSTONE SURGEONS
Cholecystectomy
According to the Danish National Board of Health, simple cholecystectomy is one of the operations that surgeons have to learn to perform at
“high level” during their training35. Approx. 50 surgeons graduate per annum. No official data exists for how many cholecystectomies a surgeon
has to conduct before s/he is deemed able to perform the operation at a
“high level”. The introduction of laparoscopic cholecystectomy has really
120
brought training into focus because it is a brand new operating technique.
The steep learning curve is used to explain the high incidence of complications526. In one study covering 8,839 cholecystectomies, it was calculated 526 that the risk of bile duct lesion was 1.7% in the first operation
performed by a surgeon, and 0.17% by operation number 50. Another
study577 showed that the curve for technical complications did not fall until after the first 30 operations. If all newly graduated surgeons in Denmark had to learn laparoscopic cholecystectomy, then the figures quoted
above would mean that approx. 1,500-2,500 (corresponding to 50-80%)
of all cholecystectomies per annum would be part of their training.
No randomised studies have been conducted into the importance of
training. A comparison between two training strategies in Japan showed
significantly fewer complications in operations carried out by the group of
surgeons who were supervised during their first ten laparoscopic cholecystectomies compared with the group who were only supervised during
the first two855. Another survey showed no difference in the complication
rates for surgeons trained “according to normal surgical training” as opposed to the same training with an extra course in laparoscopic technology and practical exercises in operations on pigs253. However, the comparison was only based on 2 x 48 operations.
Nobody is suggesting that surgeons should not be trained in the technique202. The debate is about the extent to which training should be on patients and according to the apprenticeship principle705, on patients and under mutual supervision227, on animal models457 or in specially built simulators729. A simulator is a sealed box with a full set of laparoscopic equipment. An animal liver and gallbladder are placed in the box and can be removed under circumstances that simulate an operation on a patient. This
is an inexpensive training model. It uses old instruments and the animal
livers are also cheap. In principle, the procedure can be repeated ‘infinitely’, until the surgeon has learned the technique properly. The largest
single cost involved is the surgeon’s time. This method is used in Denmark63.
A questionnaire survey in the USA50 of 285 specially selected surgeons
(response rate 52%) showed that 74% were of the opinion that training
on animal models was necessary and 66% that new surgeons should be
subjected to a supervisory period (average 12 patients) before final certification. A questionnaire survey of 1,031 surgeons in Great Britain (response rate 76%) showed that 9% had trained on animal models, 32%
had attended courses that included practical exercises, 52% had visited
121
and observed other surgeons and 67% had invited experienced surgeons
to attend their hospital 470.
Discussion
It is been discussed whether the number of surgeons who perform cholecystectomies ought to be restricted312. However, within oncological
surgery, it has been impossible to identify any relationship in traditional
open laparotomy between the number of operations per surgeon and the
success rates for the various operations 321, 363, 739. The literature suggests
that the situation may be different as far as the laparoscopic technique is
concerned526. Training in biliary tract surgery used to be part of general
surgical training, but the introduction of the laparoscopic method brought
into question the feasibility of this situation in Denmark. On the face of
it, there seems to be a disparity between the number of surgeons who have
to be trained and the number operations available to them. A debate is
needed about the structure of this complicated medical field if the health
service is to continue to concentrate on the laparoscopic method.
ERCP
ERCP also requires training and regular updates. The literature suggests
that it takes 100-120 ERCP procedures before an endoscope operator can
be considered fully trained689, 818. One survey also showed that doctors
who perform more than one sphincterotomy per week encounter fewer
complications than those who perform fewer248. This suggests a need for
centralisation, which is also foreseen in the Danish National Board of
Health guidelines36.
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11. Economy
11.1 I NTRODUCTION
The financial assessment covers the total cost of gallstone treatment in
Denmark. In order to identify the most cost-effective methods, the costs
of alternative treatments were also compared with the benefits in health
terms.
The basic elements in a financial assessment are the costs and the effects. The relevant costs were divided up into three categories:
❖
Direct costs such as wages, equipment, materials, etc. for all those involved in the
treatment.
❖
Indirect costs as a result of the loss of productivity due to illness, including lost working hours and reduced spare time for patients and next-of-kin.
❖
Intangible human costs such as nervousness about the result of the treatment,
pains, dissatisfaction, etc. which cannot be calculated in monetary value.
The costs represent the total (social) cost of a given treatment. The analyses did not include sickness benefit, pensions, etc. since these represent a
redistribution of social resources.
The consequences of the treatment (effects) is the second element in a
financial assessment. The effects can be measured in terms of: increased
longevity, improved quality of life, absence of symptoms, risk of future
complications, successful treatment, etc. A number of financial analyses
have been developed for this purpose. This report used a cost-effectiveness
analysis, which compared alternative interventions with different effects.
The decision criteria were: to choose the alternative that minimises costs
for a given effect, or conversely, maximises effects within a given budget
(efficiency).
This section calculates the direct costs of biliary tract treatment in Denmark and a number of financial analyses are made of simple cholecystectomy, which accounts for 69% of the total number of treatments in this
field.
123
11.2 D EVELOPMENTS IN TREATMENT COSTS IN D ENMARK , 1978-1995
11.2.1 All treatments for benign biliary tract disorderse
These calculations only include hospital admissions with a diagnosis related to the biliary tracts (figure 48). The costs cover bed-days, the costs
of different types of diagnostic and therapeutic operation (ERCP and
surgery) and expenses for apparatus and instruments. The calculations
were based on a questionnaire survey sent to all surgical departments and
to selected medical departments in Denmark, information about average
wages as well as prices for the purchase, maintenance and consumption of
apparatus and instruments all collated in 1997. A detailed breakdown is
presented in appendix 5. All the costs are expressed in 1997 prices in Danish kroner (DKK).
FIGURE 48
Total costs of biliary tract treatments in Denmark, 1978-1995
Costs (Mill. DKK – 1997 prices)
250
200
150
100
50
0
Year 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95
Diagnostic ERCP
Simple cholecystectomy
Cholecystectomy with bile duct treatment
Other bile duct treatment
Totalt
The total cost of treatment for biliary tract disorders fell by 46% from
1978 to 1991 (3.5% per annum) and rose by 8% until 1995 (2% per annum). The total fall from 1978 to 1995 was 41%. The only category of
treatment in which costs rose before the introduction of laparoscopic
cholecystectomy was diagnostic ERCP. The total costs in 1995 were due
124
mainly to simple cholecystectomies (55%) and endoscopic bile duct
surgery without cholecystectomy (20%).
By dividing the costs between bed-days and the actual treatment (figure 49), it becomes clear that the cost per bed-day fell by 49% from 1978
to 1991 (3.8% per annum) followed by a minor fall of 5% until 1995
(1.2% per annum). The fall during the whole period was 52%. The costs
associated with operations including equipment – remained more or less
constant until 1990, after which they rose by 146% over the whole period.
FIGURE 49
Total costs divided between bed-days and operations, 1978-1995
Costs (Mill. DKK – 1997 prices)
200
180
160
140
120
100
80
60
40
20
0
Year 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95
Costs due to bed-days
Costs due to treatment
If the costs are calculated per admission, then they decrease over the whole
period (figure 50). The fall was 3.3% per annum until 1991, after which
it accelerated to 5.6% per annum. The decrease was particularly noticeable just after the introduction of laparoscopic cholecystectomy.
125
FIGURE 50
Cost per admission, 1978-1995
Costs in Mill. DKK (1997-prices)
45,000
40,000
35,000
30,000
25,000
20,000
15,000
10,000
5,000
0
Year 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95
11.2.2 Simple cholecystectomy
The total costs for courses of treatment with simple cholecystectomy as index treatment fell by 37% (2.9% per annum) until 1991, after which the
curve flattened out and they fell slightly by 2.3% (0.6% per annum) (figure 51). If admissions three months before and one month after the index
admission are included, then the pattern does not change. Costs per patient remained the same during the first 6 years followed by a fall of 24%
(3.4% per annum) until 1991. After that they fell by 26% (6.4%/year)
(figure 52). The fall was particularly noticeable just after the introduction
of laparoscopic cholecystectomy.
126
FIGURE 51
Total costs of simple cholecystectomy, 1978-1995
Mill. DKK (1997-prices)
120
100
80
60
40
20
0
Year 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95
FIGURE 52
Cost per patient with simple cholecystectomy, 1978-1995
Costs in DKK (1997-prices)
60,000
50,000
40,000
30,000
20,000
10,000
0
Year 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95
11.2.3 Discussion
The calculations shown above are relatively rough, as they mainly focus
on the length of stay and the costs associated with the actual operation. In
127
other words, these analyses only account for a proportion of the total
costs. These components do, however, account for a significant share of
the cost of treating biliary tract disorders. If both an average bed-day price
and the direct cost of the actual operation are included, a certain amount
of double registering may occur, since the operation affects the price per
day of a hospital bed to a certain degree. However, the average bed-day
price includes all admissions to Danish hospitals separate figures are not
available for biliary tract surgery. The calculations do not include indirect
costs in the form of sick leave after the operation since no definitive data
is available about sick leave in Denmark in the period in question. As discussed later in this chapter, sick leave costs only make up a small proportion of the total costs, so they would have little effect on the conclusions.
The changes in costs for all admissions and for courses of treatment involving simple cholecystectomy can be attributed to three components:
the time spent in hospital, the number of periods spent in hospital and apparatus (ERCP and laparoscopic cholecystectomy). A significant cause of
the fall in costs until 1991 was the reduced number of days spent in hospital, which may have been due to a change in attitudes or a desire for
streamlining. Data about the number of bed-days in the National Hospital Discharge Register has proven particularly valid32.
The large number of admissions for diagnostic ERCP that do not lead
to a biliary tract diagnosis are avoided, by only including admissions registered under a biliary tract diagnosis. These admissions would weigh
heavily, since they often involve patients who are ill for a variety of other
reasons and for whom diagnostic ERCP is only one of many examinations.
The developments in Denmark correspond to those in other countries,
where unit costs have fallen but total costs have risen from 6-11% after
the introduction of laparoscopic cholecystectomy71, 438, 578.
11.3 E CONOMICAL MODELS FOR GALLSTONE TREATMENTS
In the following section, a number of alternative treatments for biliary
tract disorders are assessed by means of financial models. Financial assessments of different treatment options often start with a decision tree describing alternative strategies. Figure 53 includes an example of a decision
tree for patients with symptomatic uncomplicated gallstones. The decision
tree is used to identify the costs and to define probabilities during the
course of treatment. There are five steps in the decision analysis:
128
❖
Identification of the specific decisions and time limits.
❖
Estimation of the different results in the decision model in the light of original
studies, the literature or expert opinion.
❖
Fixing of the costs associated with the alternative treatment options and the
consequences of the alternative treatments.
❖
Setting the value of the possible outcome of the treatment.
❖
Comparing the cost efficiency of the alternatives.
FIGURE 53
Decision tree for the treatment of patients with symptomatic but uncomplicated gallstones
Patients with symptomatic
uncomplicated gallstones
Laparoscopic cholecystectomy
Minilaparotomy
Open cholecystectomy
Success
Success
Success
Complication, reoperation
Complication, reoperation
Complication, reoperation
Peripheral bile duct lesions
Peripheral bile duct lesions
Peripheral bile duct lesions
Central bile duct lesions
Central bile duct lesions
Central bile duct lesions
Conversion
Conversion
The financial models are based on data extracted from the literature, data
from the National Hospital Discharge Register and questionnaires to surgical and medical departments in Denmark (appendix 5).
11.3.1 Treatment of patients with stones in the gallbladder
Elective simple cholecystectomy accounted for 69% of all the courses of
treatment from 1978-95, making it by far the most important group in a
financial context.
129
Cholecystectomy by laparoscopy, minilaparotomy and traditional open
laparotomy
The total costs of laparoscopic cholecystectomy and cholecystectomy by
minilaparotomy were calculated on the basis of two randomised studies483,
504
. The costs were based on information in the articles about the duration
of operations; length of stay in hospital, bile duct lesions discovered after
the operation that required either re-operation or therapeutic ERCP, other
complications that required re-operation and, finally, the length of the
convalescence. The specific expenses for the individual components were
taken from Danish calculations (appendix 5). Cholecystectomy by laparoscopy was DKK 1,163 cheaper per patient than minilaparotomy in
one of the studies504, but DKK 1,210 more expensive in the other483. The
latter must in this context be considered the most valid because it was
blinded. Both the randomised surveys have been criticised for including
excessively long stays in hospital and long periods of convalescence; one
of them has been criticised for having a very high complication rate and
not being blinded504, and they constitute a very flimsy basis (approx. 500
patients), so the results should be interpreted with caution. Randomised
surveys in which cholecystectomy by traditional open laparotomy is compared with minilaparotomy and laparoscopy respectively are even more
scarce, which is why no financial analysis has been attempted on the basis of those figures.
Instead a financial model was used in which the three methods of
cholecystectomy are compared. The model was based on a number of suppositions listed in table 15.
130
TABLE 15
The baseline estimates in the model for cholecystectomy of patients with symptomatic
uncomplicated gallstones divided up according to the three methods of access.
LAPAROSCOPY
Results
Success
Probability
a
Bed-days
Costs c in DKK
Sick leave
0.8835
2
9,251
8
0.0039
7
23,513
14
Central bile duct lesion
0.0026
14
39,308
42
Conversion
0.1000
6
18,656
28
Re-operation (other cause)
0.0100
Peripheral bile duct lesion
10
29,870
28
2.53
10,532
10.31
Bed-days
Costs c in DKK
Sick leave
Average b
MIINILAPAROTOMY
Results
Probability
Success a
0.8880
2
6,169
8
Peripheral bile duct lesion
0.0017
7
20,412
14
Central bile duct lesion
0.0003
14
36,333
42
Conversion
0.1000
6
15,591
28
Re-operation (other cause)
0.0100
10
26,790
28
2.49
7,351
10.22
Bed-day
Costs c in DKK
Sick leave
Average b
TRADITIONAL LAPAROTOMY
Results
Probability
Success a
0.9870
6
15,189
28
Peripheral bile duct lesion
0.0026
7
20,423
28
Central bile duct lesion
0.0004
14
36,250
42
Conversion
0.0000
-
-
-
Re-operation (other cause)
0.0100
10
26,790
28
6.05
15,327
28.01
Average b
a: Operations which go according to plan without conversion and/or subsequent re-operation
b: The average is weighted against the probability of different results
c: Direct costs
Background for the suppositions:
❖
The prices of the operations were taken from a national survey (appendix 5).
❖
The prices for bed-days and sick leave were taken from national data (appendix 5).
❖
The incidence of peripheral and central bile lesions was derived from a systematic
literature search (table 8). Costs of treatment for peripheral lesions were estimated
to be the costs of therapeutic ERCP (since that is the most common way of treating
them), while those for central lesions were estimated to be the costs of an open
operation. If bile duct lesions are ignored, then there is no evidence to suggest that
there is any difference in the rate of re-operation among the three methods.
131
❖
Systematic study of the available literature does not suggest any particular difference in the time spent in hospital and convalescence after cholecystectomy by laparoscopy or by minilaparotomy.
❖
The length of time spent in hospital after traditional open cholecystectomy is estimated to be the median time spent in hospital according to the National Hospital
Discharge Register around the time that laparoscopic cholecystectomy was introduced (figure 35).
❖
Conversion to open surgery seems to be equally frequent for both the minimal invasive techniques 483, 504. In the event of conversion, the length of stay in hospital
and the length of the convalescence are presumed to be just as long as after traditional open laparotomy.
The model does not include operation-related mortality rates. Other costs
are, of course, associated with gallstone treatment, e.g. prehospital examinations. However, they can be assumed to be identical for all three methods and, as such, have no bearing on the results of the financial analysis.
Based on the prerequisites mentioned above, the direct costs of an unproblematic operation were DKK 9,251 for a laparoscopic cholecystectomy, DKK 6,169 for a cholecystectomy by minilaparotomy and DKK
15,189 for a traditional open cholecystectomy. The differences are due to
differences in the amount of time spent in hospital and the differences in
the cost of equipment. In the event of problems or complications, the financial consequences are adapted, paying due heed to the alternatives i.e.
conversion, re-operation or endoscopic treatment. This gives an expected
average direct cost for the three forms of access of DKK 10,532, DKK
7,351 and DKK 15,327, respectively (table 15). When calculating the indirect costs, the convalescence period was used and the costs per day of
sick leave were calculated at just under DKK 300. This figure was based
on an aggregate consisting of the average hourly wage, proportion of the
population in the workforce, proportion of the workforce in work and average number of working hours per day (appendix 5). Based on this calculation, the expected average total costs for the three methods of access
work out at DKK 13,603, DKK 10,394 and DKK 23,668, respectively
(table 16).
The effect(Ei) is the probability of a successful intervention, in this case
defined as a cholecystectomy performed without complications or other
problems for the patient. The expected costs (Ci) are calculated as the sum
of the costs for the possible results weighted against the probability of
these results. Average cost-effectiveness expresses the cost (in DKK) per
132
successful treatment (Ci/Ei) and, as such, only assesses the individual
method and does not involve the alternatives. The marginal cost efficiency
expresses the cost of increasing the probability for successful operation by
one unit. In other words, the ratio for the difference in costs and the effects between the two alternatives (Clap. – Cmini/Elap – Emini).
TABLE 16
Result of the financial model for cholecystectomy
Cost effectiveness
Expected effect (E)
Expected costs (C)
Average (C/E)
11,920
Marginala
Direct costs only for cholecystectomy by
Laparoscopy
0.8835
10,532
Minilaparotomy
0.8880
7,351
8,278
Traditional laparotomy
0.9870
15,327
15,529
46,334
Both direct and indirect b costs for cholecystectomy by
Laparoscopy
0.8835
13,603
15,396
Minilaparotomy
0.8880
10,394
11,705
Traditional laparotomy
0.9870
23,668
23,979
97,246
a: The costs of increasing the probability of a successful operation by one unit (for example: Clap.-Cmini/Elap.-Emini).
The data was compared with laparoscopic cholecystectomy
b: The indirect costs were calculated by multiplying the average sick leave by DKK 297.81 (appendix 5)
The estimates in tables 15 and 16 show that cholecystectomy by minilaparotomy is both better (in the sense of a higher success rate) and cheaper
than laparoscopic cholecystectomy, while cholecystectomy by open laparotomy is better (fewer bile duct lesions) than by laparoscopy but also
more expensive. In the latter comparison, there is a so-called dominant solution, in which it is relevant to calculate the cost by increasing the probability that an operation will be a success (the marginal cost effectiveness).
According to table 16, the price is just under DKK 100,000.
If it is assumed that 75% of all simple cholecystectomies are laparoscopic and the calculation is based on the expected average total costs in
table 16, it can be calculated that the total saving by switching from laparoscopic cholecystectomy to cholecystectomy by minilaparotomy in
Denmark would be just under DKK 8 million per annum.
Sensitivity analysis
The assumptions used in the model can always be discussed. In order to
comply with well-founded objections and test the durability and conclusions of the model, a number of sensitivity analyses were conducted in
which the central prerequisites were varied. The preconditions can be var-
133
ied infinitely and some examples will be given in the next section. In appendix 5 (table 5 and 6) a number of estimates have been calculated by
changing the direct and indirect costs as well as the prices for days spent
in bed and convalescing.
Changes in prices
Even relatively major changes in the prices do not change the conclusion.
Minilaparotomy still comes out better (fewer bile duct lesions) and
cheaper than laparoscopy, and traditional open laparotomy is still better
(fewer bile duct lesions) but more expensive than laparoscopy. By reducing the price per day of a hospital bed to DKK 1,000, traditional open laparotomy does, however, become almost as cost-effective as laparoscopy.
The unit price for the laparoscopic columns is calculated at approximately
DKK 2,000. Even if this price were lowered which would correspond to
performing more operations per column laparoscopic cholecystectomy
would never turn out cheaper than cholecystectomy by minilaparotomy
(figure 54). Conversely, the figure shows that in departments that perform
very few cholecystectomies per annum (approximately 20) the cost of laparoscopic cholecystectomy approaches that of traditional open cholecystectomy.
FIGURE 54
Adjustment of the unit cost for laparoscopic columns
Costs per success
18,000
16,000
14,000
12,000
10,000
8,000
6,000
4,000
2,000
0
Unit price
500
CE-lap
134
1000
1500
CE-minilap
2000
2500
CE-open
3500
Changes in the number of days spent in bed and convalescing
A difference in the time spent in hospital between minilaparotomy and laparoscopy might offer up different conclusions, as a difference of over two
days would make laparoscopic access cheaper than minilaparotomy. If the
true time spent in hospital for laparoscopic cholecystectomy is three days,
then the number of bed-days would have to rise to five days for cholecystectomy by minilaparotomy, before laparoscopy would be the least expensive solution. If, on the other hand, the stay in hospital was three days
for minilaparotomy, then the time spent in hospital for a laparoscopic operation would have to be reduced to one day before it would be the least
expensive solution.
The time spent convalescing is not as significant. For example, sick
leave after cholecystectomy by minilaparotomy would have to rise to 21
days instead of 8, before laparoscopic cholecystectomy would be cheaper.
Changes in the number of complications
The final option is to change the estimates of the number of complications. Even if the success rate for laparoscopic cholecystectomy was raised
to 1 in other words all laparoscopic cholecystectomies would have to be a
success without any complications, conversions or re-operations then
cholecystectomy by minilaparotomy would still have the lowest expected
cost (DKK 10,394 versus DKK 11,633).
Conclusion
Laparoscopic cholecystectomy is only cheaper than cholecystectomy by
minilaparotomy if the difference in number of days spent in hospital is
more than two. Even in a hypothetical situation without conversion or
complications to laparoscopic cholecystectomy, minilaparotomy would
still be a better financial alternative.
Discussion
A number of articles have dealt with economical analyses that calculated
the costs of alternative procedures. The majority of them compared traditional open cholecystectomy with the laparoscopic procedure. The majority only analysed actual hospital costs. Bearing in mind the differences
in the way the studies were designed American surveys, in particular, are
based on the hospitals’ prices, which do not necessarily reflect the real
costs – as well as the operation itself and the time perspective, an ambiguous picture emerges. Laparoscopic cholecystectomy varies from ap-
135
prox. 60% cheaper to 30% more expensive compared with open surgery718, 752, 803. However, hospital costs tend to be lower for the laparoscopic procedure because of the shorter stay in hospital26, 153, 258, 307, 387, 452,
501, 606, 686, 835
.
As far as the scope of financial assessments that explicitly compare the
costs with effects are concerned, the literature is more limited. A cost-minimisation analysis comparing laparoscopic and traditional open cholecystectomy concluded80 that traditional open cholecystectomy is cheaper
than laparoscopy in regard to hospital costs. If direct and indirect costs are
included, the laparoscopic procedure proves to be the best alternative in
financial terms – subject, however, to a minimum of 68 patients per annum because of the investment costs for laparoscopic equipment. This
conclusion was supported by another study67, which, however, found the
conclusion to be sensitive to changes in the estimates.
One argument against the financial models presented here is the way
in which the model is constructed, i.e. with some estimates of probability
taken from the literature and others calculated specifically for the purposes of this report. This method of constructing models involves a number of elements of uncertainty. The sensitivity analyses do, however, take
this into account by adapting the values applied. As mentioned above, the
information used about the frequency of complications after cholecystectomy was based on retrospective results and have to be interpreted with
caution. However, the sensitivity analyses showed that even without conversions or complications to laparoscopic surgery, cholecystectomy by
minilaparotomy would still be the best alternative in financial terms.
As stated, it has not been possible to take into account the intangible
costs. However, there was no difference in, for example, general satisfaction and persistent pains some months after the operation505. Patients did
tend to be more satisfied with their scars 12 weeks after laparoscopic
surgery than after minilaparotomy (10 cm)504.
Disposable versus reusable instruments for laparoscopic cholecystectomy
The instruments used for laparoscopic removal of the gallbladder are
available in disposable and reusable forms. A simple cost breakdown concluded that disposable instruments are 7-12 times more expensive to use
than reusable instruments even when maintenance costs for the reusable
instruments are factored in327. Disposable instruments cost between DKK
3,911 and DKK 5,560. (including special agreements and volume discounts). The purchase price for a set of reusable instruments is around
136
DKK 32,000 (1996 prices), which gives a unit cost per operation of between DKK 479-834 including cleaning and maintenance costs327. However, a randomised survey has shown that the use of disposable instruments causes significantly fewer surgical/technical problems and an insignificant tendency towards faster operations and fewer conversions to
open surgery than reusable instruments588. Despite these differences,
reusable equipment was on average some DM 1,000 cheaper to use. Another survey found similar differences437. Common for both surveys was
that they did not link the higher cost of surgical equipment directly with
the potential benefits of using them. The next section consists of a cost-effectiveness analysis of the use of disposable versus reusable equipment.
An economic model
In this model, technical problems with instruments are included under the
term ‘successful treatment’, since they have no adverse effect on the patient’s health. Technical problems cause longer operations, which have
been incorporated into the model. The costs of a successful operation consist of the actual surgical equipment, surgical staff costs and days spent in
bed. The financial consequences of the alternative results would consist
mainly of longer operations and extra days in bed. The increased number
of bed-days as a result of the different clinical situations and their respective probabilities are included in table 17.
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TABLE 17
The baseline estimates in the model for the use of disposable or reusable equipment for
laparoscopic cholecystectomy.
DISPOSABLE EQUIPMENT d
Operation result
Probability
a
Success
Bed-days
Costs c
Sick leave
0.7686
2
11,591
8
Surgical/ technical problem
0.1533
2
12,035
8
Post-operative complication
0.0122
5
18,356
10
Central bile duct lesion
0.0026
14
42,314
42
Conversion
0.0635
6
20,833
28
2.32
12,407
9.38
Bed-days
Costs c
Sick leave
Average b
REUSABLE EQUIPMENT d
Operation result
Probability
Success a
0.5494
2
7,131
8
Surgical/ technical problem
0.3119
2
7,575
8
Post-operative complication
0.0494
5
13,896
10
Central bile duct lesion
0.0026
14
37,853
42
Conversion
0.0869
6
16,373
28
2.53
8,485
9.93
Average b
a:
b:
c:
d:
Operations that go according to plan without conversion and/or subsequent re-operation
The average is weighted against the probability of different results
Direct costs
The unit price for disposable equipment is DKK 5,560 and for reusable equipment: DKK 834.
The cost per day of sick leave was calculated at just under DKK 300 (appendix 5). The economical model (table 18) shows that disposable equipment is better but also more expensive. The marginal cost efficiency of
some DKK 64,000 shows the monetary value (the alternative cost) of using the next best alternative (reusable instruments). The total financial
analysis shows that as far as the expected costs are concerned, the use of
disposable instruments costs some DKK 9 million more per annum in
Denmark than the use of reusable instruments would cost. This calculation is based on the number of simple cholecystectomies in 1995 and under the proviso that 75% of all cholecystectomies were laparoscopic.
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TABLE 18
Results from the financial model for comparison of disposable and reusable equipment.
Cost effectiveness
Expected effect (E)C
Expected costs (C)
Average (C/E)
Marginala
64.719
Direct costs only for laparoscopic cholecystectomy using
Disposable equipment
0,9218
12.407
13.460
Reusable equipment
0,8612
8.485
9.853
Both direct and indirect b costs for laparoscopic cholecystectomy using
Disposable equipment
0,9218
15.200
16.489
Reusable equipment
0,8612
11.442
13.286
62.013
a: The costs of increasing the probability for successful operation by one unit (for example: Cdisp-Creus/Edisp-Ereus).
The data is compared with reusable equipment
b: The indirect costs are calculated by multiplying the average sick leave by DKK 297.81 (appendix 5).
c: The expected effect includes successful operation as well as technical problems with the instruments (see text).
Sensitivity analyses
To assess the durability of the model and, therefore, the conclusions, a sensitivity analysis was conducted during which the model estimates were
varied. It would be possible to use an infinite number of alternatives and
combinations of both probabilities and cost targets. Variations are made
in the probabilities of clinical events, the price per day of a hospital bed,
the price of the equipment, the staff costs plus the time spent in hospital,
while other parameters remain constant. Some of the estimates are listed
in table 7, appendix 5.
As far as the price per day of a hospital bed and the staff costs are concerned, reusable equipment will still be the best financial alternative unless prices are multiplied, which is unrealistic.
The price for a complete set of disposable equipment would have to be
lower than DKK 1,639 before the disposable equipment would become
the least expensive alternative or, conversely, the costs associated with
reusable equipment would have to exceed DKK 4,756 per operation.
If the success rate for disposable instruments is set at 1 (i.e. every treatment a success with no conversions), then the total direct costs would be
exactly DKK 11,591, which is still higher than for the reusable instruments.
Conclusion
Reusable equipment is the least expensive solution, even if it does cause
more conversions and subsequent longer stays in hospital and longer convalescence. The price of disposable instruments would have to fall below
DKK 1,700 per operation for this alternative to be cheaper and better than
139
reusable instruments. It would not be feasible to try and put a value on the
extra level of job satisfaction the staff would experience using disposable
equipment.
Cholecystectomy versus ESWL
Two studies compared ESWL with laparoscopic and traditional open
cholecystectomy153, 281. In a cost-utility analysis153, the laparoscopic procedure was found to be the best alternative, since it cost less and the effects
were better. On the other hand, the results were sensitive to the inclusion
of, for example, indirect costs. In a sort of cost-effectiveness analysis281 it
was concluded that the laparoscopic procedure is the most cost-effective
procedure for the majority of patients with symptomatic gallstones, while
ESWL seems to be more or just as cost-efficient as traditional open cholecystectomy; especially for elderly patients828 and patients with small gallstones221, 565. In 1990, the Swedish Institute for Medical Technology Assessment (SBU) assessed gallstone treatments based on the use of ESWL30.
One of their conclusions was that the costs associated with shock wave
treatments were reasonable in relation to the other alternatives and this
method ought, therefore, to be tested in-depth.
Conclusion
While ESWL seems to be more cost-efficient than traditional open cholecystectomy, laparoscopic cholecystectomy is superior to ESWL. No financial comparisons were traced that compare ESWL with cholecystectomy
by minilaparotomy.
11.3.2 Treatment of patients with acute cholecystitis
The early strategy versus the later strategy for cholecystectomy in the event
of acute cholecystitis does not need to be subjected to a comprehensive financial analysis, since all the randomised studies unanimously showed that
the early strategy entailed less time spent in hospital and shorter convalescence periods with no difference in the complication rates (page 95).
This patient category constitutes a large proportion a total of 21% of
all treatments from 1978-95. It would have been interesting to assess the
financial consequences of different strategies in the form of immediate operation, drainage in conjunction with subsequent operation and drainage
alone followed by operation if necessary at a later phase. However, the literature in the area is so sparse that a responsible model could not be constructed.
140
Similarly, the literature does not contain sufficient information to assess the financial consequences of different methods of cholecystectomy in
the event of acute cholecystitis.
11.3.3 Treatment of patients with stones in the bile ducts
The proportion of courses of treatment primarily involving bile duct disorders was 27%.
Screening for choledochal stones during cholecystectomy
The following three strategies were compared for the examination of patients for stones in the bile ducts during cholecystectomy: preoperative
ERCP for all patients, intraoperative cholangiography for all patients and
intraoperative cholangiography for selected patients where there is particular reason to suspect choledochal stones. Selective intraoperative cholangiography proved the most cost-effective strategy702. Choledochoscopy as
a means of searching for residual choledochal stones was not cost-effective548.
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12. Summary of the elements
in the Health Technology
Assessment
This chapter summarises the four elements of a health technology assessment – the technology, the patient, the organisation and the finances. The
chapter can be read independently along with the synthesis in chapter 13.
References do, however, only figure in the main report and appendices.
12.1 D EVELOPMENTS IN THE INCIDENCE AND TREATMENT OF GALLSTONES
Gallstones
Gallstones are common in America, Europe, Australia and large parts of
Asia, while they are rare in the Far East and Africa. Twice as many women
have gallstones as men. The greatest risk factor among women is pregnancy, which probably accounts for most of the gender difference. The
other risk factors are closely related to Western lifestyle, e.g. low-fibre and
fatty foods, lack of exercise, obesity, smoking and type-2 diabetes.
As a rule, stones in the gallbladder do not provoke symptoms. The clinical spectrum stretches from this asymptomatic condition, which often
lasts for the rest of the patient’s a life; to symptomatic gallstones, which
are unpleasant but benign; to gallstone complications in the form of infection of the gallbladder, stones in the bile ducts and pancreatitis. As a
rule, the complications can be dealt with easily enough, but on rare occasions they can be life-threatening or disabling.
Developments in treatment
In the early 70s, work started on the development of a whole series of
technologies that changed the traditional methods of treating gallstone
patients. The most important technologies are summed up in figures 55
and 56. The year denotes the year of publication in the international literature.
As a rule, the technologies were introduced after clinical testing but
were not tested right away in randomised studies to compare their roles in
treatment strategies for gallstone patients. A lot of technologies were introduced because they were considered to entail less hardship for the pa-
142
tient. Later, randomised studies have, however, questioned whether this is
in fact the case. There was also an inexplicable rise in the number of operations and a suspected increase in the number of complications in the
form of lesions of the bile ducts after the introduction of laparoscopic
cholecystectomy.
FIGURE 55
The introduction of different technologies for the treatment of stones in the gallbladder
Year of publication
Technology
1867
Surgical removal of stones in the gallbladder (cholecystolithotomy)
1882
Surgical removal of the gallbladder (cholecystectomy)
1955
Surgical removal of stones in the gallbladder by minilaparotomy
1972
Bile salts to dissolve stones in the gallbladder
1980
Ultrasonic puncturing of the gallbladder
1982
Surgical removal of the gallbladder by minilaparotomy
1985
Percutaneous removal of stones in the gallbladder through a probe inserted ultrasonically
1985
Dissolution of gallbladder stones with ether and flushing out through probe
1985
Pulverisation of gallbladder stones with sound waves (ESWL)
1986
Laparoscopic removal of the gallbladder
1991
Laparoscopic removal of stones in the gallbladder
FIGURE 56
The introduction of different technologies for the treatment of stones in the bile ducts
Year of publication
Technology
1890
Surgical removal of stones in the bile ducts (cholecystolithotomy)
1970
Diagnostic ERCP
1974
Removal of stones in the bile ducts after sphincterotomy by ERCP
1982
Surgical removal of stones in the bile ducts by minilaparotomy
1988
Dissolution of stones in the bile ducts by ether
1990
Contact pulverisation of stones in the bile ducts
1991
Laparoscopic removal of stones in the bile ducts
1992
Pulverisation of stones in the bile ducts by sound waves (ESWL)
1994
Removal of stones in the bile ducts after balloon angioplasty of the bile duct sphincter
With these developments in mind, the author, the National Institute of
Public Health (NIPH) and the Danish Institute for Health Technology
Assessment decided it would be relevant to conduct a health technology
assessment of gallstone treatments. An HTA is a comprehensive, systematic evaluation of the preconditions for, and consequences of, using
health technologies.
143
12.2 M ATERIAL AND METHODS
The National Hospital Discharge Register
All admissions registered in the National Hospital Discharge Register between 1978-95 with a treatment code related to biliary tracts were extracted. After excluding cancer of the liver, pancreas and biliary tracts,
99,803 admissions were left, spread between 87,007 patients. A more indepth study of the admissions identified the number of courses of treatment – a total of 90,582 because some patients could have more than one
course. Among the 90,582 courses of treatment, 12,262 consisted exclusively of diagnostic ERCP. The remaining 78,320 courses of treatment
were classified in the following categories:
❖
Simple cholecystectomy. This category makes up the vast majority (69%) and represents patients who only had their gallbladders removed.
❖
Cholecystectomy with simultaneous bile duct treatment. The bile duct treatment
was either endoscopic, by open surgery or by biliodigestive anastomosis. The category represents patients who were treated for stones both in the gallbladder
and the bile duct but also includes patients who suffered complications to a simple cholecystectomy.
❖
Bile duct treatment without simultaneous cholecystectomy. Bile duct treatment
can be by endoscopic surgery, open surgery or biliodigestive anastomosis. The category includes patients who either only suffer from stones in the bile ducts (they
may have had a cholecystectomy earlier) or who do not need to have the stones in
their gallbladder treated at the same time.
❖
Other treatments.
The vast majority of patients were only admitted to hospital once but
some were readmitted later for one or more new biliary tract procedures.
Patients who were readmitted usually suffered either a complication to
their biliary tract disease or a complication to the primary treatment.
The validity of the information from the National Hospital Discharge
Register was tested by extracting 3,570 commentaries from the respective
hospitals. The response rate at the time we were going to press was 71%.
As far as the surgical operations such as cholecystectomy and open bile
duct surgery are concerned, there level of validity was particularly high
(above 95%), while therapeutic ERCP was underreported throughout the
period. The importance of the underreporting has increased over the
years, which means that the increase in bile duct treatment in the 90s was
greater than stated in the report.
144
Literature
An in-depth study of the available literature was conducted in order to assess the evidence of the different technologies for the treatment of biliary
tract disorders. The scientific literature dealing with the treatment of gallstone patients is very comprehensive. In order to avoid bias in the selection of the literature and consequently in the conclusions, the report followed fixed criteria. A total of more than 23,000 abstracts were studied
and more than 3,000 articles reviewed.
Danish population studies
Since 1982, several screening have been done for gallstones in Danish
populations. A total of 5,936 randomly selected people were scanned by
ultrasound for gallstones. The results of these examinations make it possible to assess the occurrence of gallstones in the Danish population.
Staff costs and time spent treating gallstone patients
For use in the financial analyses, a questionnaire was sent to all surgical
departments in 1997 (response rate 67%) and selected medical departments (response rate 100%). A number of questions were posed to help
estimate staff costs and time spent on different biliary tract operations.
12.3 O CCURRENCE , NATURAL HISTORY AND PREVENTION
In Denmark, approximately 10% of the population have gallstone disorders (both people who have undergone a cholecystectomy and those who
have stones in the gallbladder). The vast majority of people with gallstones have no symptoms, so it is estimated that approximately 300,000
people in Denmark have stones in the gallbladder but are not aware of
them. The proportion of the population with gallstone disorders has declined in the 80s but not significantly.
People with asymptomatic gallstones and symptomatic gallstones develop complications with a frequency of 0.2-1.2% and 0.7-2.0% per annum, respectively. These low levels of risk show that gallstones are a relatively harmless condition. Thus, there is no great risk associated with
waiting to see what happens in respect to gallstone patients.
No documentary knowledge exists of the extent to which modifying
the lifestyle factors that increase the risk of gallstone formation effects the
incidence of gallstones (primary prevention). Prevention of cardiovascular
disease focuses on lifestyle factors that also affect gallstone formation.
Changes in lifestyle in recent years may have caused the reduction in the
145
incidence of gallstones. Severe weight loss can cause gallstones to form. It
has been proven that formation of gallstones can be reduced significantly,
if bile salts are administered to overweight patients during rapid weight
loss.
Secondary prevention identifies and removes gallstones before symptoms or complications develop. It is generally agreed that cholecystectomy
is not well-suited as secondary prophylaxis because it has been calculated
that operating has a tendency to increase the mortality rate compared with
not operating. The extent to which medical dissolution of asymptomatic
gallstones as secondary prophylaxis is cost-effective has not been studied.
The method requires samples of the population to be screened for gallstones, which requires identification of high-risk groups. Pregnant women
would be one relevant target group, as pregnancies are the largest single
risk factor for lithiasis in women. No studies have been conducted of the
potential for secondary prophylaxis among pregnant women.
12.4 O VERALL TREATMENT OF BILIARY TRACT DISORDERS IN D ENMARK
From 1978 to 1991, when laparoscopic cholecystectomy was introduced
in Denmark, the rate of treatment for biliary tract disorders (number
treated per 100,000 of the population) fell steadily. The rate fell 30% for
women and 21% for men. After 1991, the rate rose 25% for women and
22% for men. There is no evidence to suggest a corresponding rise in the
incidence of biliary tract disorders. The rise may be due to the change in
indications when laparoscopic cholecystectomy was introduced. The increase in the frequency of treatment included both simple cholecystectomy
and treatment for bile duct diseases. Also the frequency of diagnostic
ERCP rose, especially after the introduction of laparoscopic cholecystectomy. The rise may reflect a changed strategy for the diagnosis and treatment of gallstones, if ERCP to a certain extent replaced intraoperative
cholangiography as a method of examination for stones in the bile ducts.
The rise in ERCP may also reflect changed indications for the examination of patients.
12.5 T REATMENT OF PATIENTS WITH UNCOMPLICATED GALLBLADDER STONES
Developments in Denmark, 1978-95
After a stable period from 1978-84, the cholecystectomy rate fell steadily
until 1991. The fall was 21% for women and 26% for men. After 1991
the rate rose 27% for women and 18% for men. The rise was particularly
pronounced for women under 40, i.e. almost 50%. The cholecystectomy
146
rate increases with age but the curve for women also peaks at around 30,
which may be due to gallstones formed during pregnancy. The top of the
curve was more pronounced in the last sub-period studied, which may
have been due to a higher degree of diagnosing. The fall in the cholecystectomy rate until the introduction of laparoscopic cholecystectomy, as
well as the subsequent rise, correspond to findings abroad. The rise in certain areas of the USA was greater than in Denmark, but compared with
three national surveys in Canada, Scotland and Australia, the rise was
greatest in Denmark.
In some areas of Denmark more than twice as many operations are
performed as in other areas – after taking account of random variation
and age differences in the population. The variations were greatest at the
start of the period and after the introduction of laparoscopic cholecystectomy. The variation – which has also been experienced abroad – reflects
differences in overall ill-health, patient behaviour and disagreement
among doctors about the indications for diagnostics and treatment.
Which symptoms are due to stones in the gallbladder
There is a great deal of disagreement about which symptoms can be ascribed to gallstones. This is due partly to the fact that 30-40% of the population have symptoms in the abdomen and that up to 20-30% have
stones in the gallbladder, giving rise to random coincidence. A systematic
review was conducted of the literature on symptoms in persons with and
without gallstones as well as persons with persistent pains after cholecystectomy. The following conclusions were reached:
❖
Hours lasting attacks of severe pains in the upper right-hand side of the abdomen
or the epigastrium may be associated with gallstones. The pain starts relatively
abruptly and may radiate out to the back or right shoulder. These symptoms are
relatively rare. However, the symptoms also occur in people without gallstones.
Thus, it is not possible to specify a watertight definition of when these symptoms
are due to gallstones and when they are not.
❖
Other abdominal pains are probably not due to gallstones.
❖
Dyspeptic pains are not caused by gallstones
Indications for treatment
Regional, historical and international variations in cholecystectomy rates
can be interpreted as disagreement among both patients and doctors
about when there is an indication for examination and treatment of gall-
147
stones. This is confirmed by studies of the disagreement among expert
panels about when there is an indication for the treatment of patients with
gallstones. The only audit carried out on patients showed that two expert
panels only agreed with the surgeon’s indication in approximately half of
the cases. These circumstances, combined with the fact that many patients
suffer persistent pains after cholecystectomy, suggest that too many cholecystectomies are performed. Instead of regular audits, it has been proposed that the guidelines be programmed into computer software which
could store data about all patients with gallstones. This would register the
department’s practice in relation to the recommended guidelines.
Methods of treatment
The technologies used to treat stones in the gallbladder are: cholecystectomy, cholecystolithotomy and dissolution/pulverisation. The primary
purpose of the treatment is absence of pain, the secondary purpose is to
remove the gallstones. The importance of the different technologies for
post-operative pains, length of time spent in hospital, complications,
length of convalescence and mortality are described below.
Cholecystectomy
Cholecystectomy is the most common treatment for patients with symptomatic gallstones. The method can either be traditional open laparotomy,
minilaparotomy or laparoscopy. The length of the incisions are respectively >10 cm, 3-6 (10) cm and 3-4 cm. The proportion of patients who
suffer persistent pains after 1-2 years is typically 20-25%, regardless of the
method. Thus, the length of the incision has no significance as far as the
primary purpose of the treatment is concerned. All three methods remove
the gallstones, but in some cases gallstones are lost in the abdominal cavity during laparoscopic cholecystectomy. These stray gallstones rarely
cause problems but any problems they do cause can be serious.
The length of the stay in hospital has fallen steadily since 1978 in Denmark and was 6-7 days before the introduction of laparoscopic cholecystectomy. When laparoscopic cholecystectomy was introduced, there was
a further reduction in the number of days spent in hospital. A number of
articles have been published about clinical series covering all three methods in which patients were sent home the same day or the day after their
operation. Double-blinded randomised studies (i.e. both patient and staff
blinded with the aid of a dressing covering the whole abdomen) revealed
no difference in the length of hospital stay for the three different methods.
148
In non-blinded randomised studies, no difference was detected between
minilaparotomy and laparoscopy, but patients did spend longer time in
hospital after traditional open cholecystectomy.
Bile duct lesions are among the most serious complications associated
with cholecystectomy. The lesions are divided up into central bile duct lesions, which are the most serious since they can cause contraction of the
bile duct and affect the liver, and peripheral bile duct lesions, which require treatment, but which rarely cause contraction of the bile duct. The
randomised trials were too small to assess differences in complication
rates between the three methods of access. Systematic reviews of clinical
series published in the international literature revealed that central bile
duct lesions occur in 0.26-0.52% of laparoscopic cholecystectomies, and
in 0.03-0.13% of open cholecystectomies (traditional open laparotomy
and minilaparotomy). The corresponding numbers for peripheral lesions
are 0.28-0.57% and 0.10-0.26%. A number of international studies also
revealed a distinct rise (4-6 times) in the number of bile duct lesions after
the introduction of laparoscopic cholecystectomy. The proportion of lesions fell a couple of years after the introduction of the laparoscopy, but
not to the same level as before the introduction. During the validation of
the information in the National Hospital Discharge Register, it was found
that there was also a rise in both central and peripheral bile duct lesions
in Denmark after the introduction of laparoscopic cholecystectomy. Studies from the national register for laparoscopic cholecystectomy suggest
that no subsequent fall in the number of bile duct lesions has occurred in
Denmark.
One argument in favour of the introduction of laparoscopic cholecystectomy was that patients could return to work sooner. A systematic review of the international literature shows that informed and motivated
patients can return to work quickly, even after traditional open surgery.
Randomised trials show no difference in the length of convalescence after
cholecystectomy by laparoscopy or minilaparotomy, while the convalescence is longer after traditional open laparotomy. When laparoscopic
cholecystectomy was introduced, attention was focused on short convalescence but there is no documentary evidence to show whether it was the
laparoscopic procedure or the attitudes of staff and patients that made the
convalescence shorter.
The mortality rate did not change after the introduction of laparoscopic cholecystectomy – either in Denmark or abroad.
149
Some chronic sequelae after cholecystectomy have been described,
which may be a consequence of the procedure. A small group of patients
experience persistent pains that call for a diagnosis and treatment not covered by fixed procedural guidelines. The absence of the gallbladder causes
increased reflux of bile to the stomach and oesophagus, which may be the
cause of the very high incidence of dyspeptic discomfort in people who
have had a cholecystectomy. Neither of the sequelae depend on the access
for cholecystectomy.
Cholecystolithotomy
Cholecystolithotomy can be performed either by traditional open surgery,
by minilaparotomy, by laparoscopy and by percutaneous insertions of
probes followed by pulverisation with laser or ultrasound or direct dissolution with medicinal substances. Some of the operations can be performed under local anaesthesia. The method is used only to a limited extent (<2% of the operations in Denmark) and is reserved mainly for patients who are too sick to tolerate anaesthesia and for patients who wish
to preserve their gallbladder.
The primary purpose of the treatment, absence of pain, is achieved as
often as it is achieved by cholecystectomy. The secondary purpose of the
treatment, removal of stones, is achieved in the vast majority of cases but
stones recur in approximately half of the patients. Complications consist
mainly of leakage of bile from the gallbladder. There is no description of
bile duct lesions in association with the procedure. The clinical series were
too small and the groups of patients too selective to assess the length of
stay in hospital, the length of convalescence and the mortality rate. No
randomised trials exist which compare the different methods of cholecystolithotomy.
ESWL/bile salts
Pulverisation of gallstones with ESWL ought to be followed by treatment
with bile salts lasting 1/2-2 years. The treatment is only suitable for 20%
of gallstone patients, as a number of preconditions have to be fulfilled.
The method is widespread abroad but has not been used particularly often in Denmark.
The primary objective of the treatment, absence of pain, is achieved to
the same degree as it is achieved by cholecystectomy. Absence of pain has
– for inexplicable reasons – nothing to do with whether the stones are pulverised or not. Stones are pulverised in over 60% of the patients, but in
150
approximately half of them stones reoccur. However, many patients remain asymptomatic for a long time after the stones reform. Routine use of
ESWL and bile salts would have a lasting effect on 5% of all gallstone patients, while a further 5% would experience a long-term effect in the form
of absence of pain. Of the potential complications, stones stuck in the bile
duct with ensuing pancreatitis is the most serious and occurs in 1-2% of
cases. The extent of sick leave and hospitalisation correspond to out-patient treatment and potential complications.
Comparisons between cholecystectomy, cholecystolithotomy and ESWL/
bile salts
No randomised trials exist which compare cholecystectomy with cholecystolithotomy. There are three randomised trials which compare cholecystectomy with treatment by ESWL/bile salts. As far as absence of pain
is concerned, they reveal no differences. The observation period was,
however, too short.
Cholecystectomy in patients with pains but without gallstones
A small group of patients has gallstone-like pains without having gallstones. Some of these patients suffer from abnormal emptying of the gallbladder. The literature reveals that cholecystectomy achieves the primary
purpose of the treatment in these patients, i.e. absence of pain, just as often as cholecystectomy in patients with gallstones. In order to avoid
overtreatment, the indication for treatment should be subjected to very
strict guidelines. Further studies are required.
12.6 T REATMENT OF PATIENTS WITH ACUTE CHOLECYSTITIS
The operation rate for acute cholecystitis in men remained the same, while
it rose for women until 1987, followed by a fall in the subsequent period.
The development reflects the generally conservative attitude towards
cholecystectomy in 80s. As a result, a higher proportion of those operated
had acute cholecystitis. A new technology emerged during the period studied, i.e. ultrasonic drainage of the gallbladder. Since this treatment does
not have an independent code in the National Hospital Discharge Register, the proportion with acute cholecystitis has been underreported. Elderly patients in particular are only treated by drainage, which may explain the fall observed in operation rates in this group of patients in the
second half of the period studied.
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There is always indication for treatment in patients with acute cholecystitis either in the form of antibiotics, drainage or surgery.
The technologies used to treat acute cholecystitis are cholecystectomy,
cholecystolithotomy, partial cholecystectomy or drainage with or without
dissolution or pulverisation of the stones. The primary purpose of the
treatment is to stop the acute infection. The secondary purpose is to stop
acute cholecystitis recurring.
Patients with complications to an acute cholecystitis (for example perforated cholecystitis) have to be operated acutely. Randomised trials have
shown that it is preferable to operate on patients with uncomplicated
acute cholecystitis during the same stay in hospital instead of letting the
infection recede and operate some months later. The sub-acute operation
ought, however, to take place not more than 7-10 days after the initial
symptoms, otherwise the changes are so pronounced that the risk of complications increases. Randomised studies have shown that treatment with
non-steroid anti-inflammatory drugs delays or stops acute cholecystitis
becoming more serious.
Cholecystectomy can be performed by traditional open laparotomy,
minilaparotomy or laparoscopy. Apart from one single open randomised
survey, which showed that minilaparotomy is better than traditional laparotomy, there is no evidence to prove which method of incision is best.
Complications in the form of lesions of the bile ducts are seen more often
in acute than in elective cholecystectomy. The mortality rate after simple
cholecystectomy for acute cholecystitis did not fall in Denmark after the
introduction of laparoscopic cholecystectomy.
Cholecystolithotomy or partial cholecystectomy can be performed, if
the anatomical conditions are complicated or if the patient is very sick and
cannot tolerate a general anaesthetic.
Ultrasonic drainage can make cholecystitis recede faster. However, it is
not known whether there is anything to be gained by draining an acute
cholecystitis, if a cholecystectomy is to be performed within a couple of
days of the drainage. Further research is required.
12.7 T REATMENT OF PATIENTS WITH STONES IN THE BILE DUCTS
Treatment rates for stones in the bile ducts fell by 30% for women and by
13% for men from 1978-91, then rose by 22% for women and 31% for
men until 1995. The curves conceal a fall in the proportion of patients
who underwent surgery and a rise in the proportion of patients who were
treated endoscopically. The fall in the number of patients who received
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bile duct treatment in the 80s and the subsequent rise in the 90s may be
due to changed attitudes to routine examinations for stones in the bile
ducts in connection with cholecystectomy (see below).
The need for examination and treatment of stones in the bile ducts is
indicated when the patient suffers symptoms of stones in the bile ducts.
There is, however, no need for routine examination of the bile ducts in
connection with cholecystectomy. Only if certain requirements are fulfilled (dilated choledochus, liver symptoms , acute pancreatitis), should a
bile duct examination be performed in connection with a cholecystectomy. Thus, examinations of the bile duct can be avoided in 80% of patients who have a cholecystectomy. The risk involved in routine examination is that it can lead to unnecessary operations on the bile ducts because
of unfounded suspicions of stones or discovery of small stones, which
would have passed by themselves.
Besides intraoperative cholangiography and ERCP a new technology
MRC (magnetic resonance) has been developed for examining bile ducts.
In contrast to ERCP, it is non-invasive and does not, therefore, cause the
complications that ERCP does. Provisional surveys suggest that the diagnostic safety of MRC is on par with ERCP, but financial surveys are required, since the equipment is expensive.
The treatment technologies in use are a) surgical removal (traditional
open bile duct surgery, minilaparotomy bile-duct surgery and laparoscopic bile duct surgery) and b) endoscopic removal (via ERCP or percutaneous methods). The primary purpose of treatment is to provide an outlet for the bile, while the secondary purpose is to remove the gallstones.
No studies have compared the three surgical methods. Minilaparotomy has only been tested casuistically and the laparoscopic method
seems to be difficult and has not become as widespread as laparoscopic
cholecystectomy.
The endoscopic method of treatment has become widespread but a
whole series of supplementary technologies for the endoscopic treatment
of complicated bile duct stones (stones that cannot be removed by a simple sphincterotomy) have made it difficult to keep tabs on all the literature
in this field. There is no documentary evidence in favour of cholecystectomy after successful endoscopic treatment.
A number of randomised trials in which open surgery was compared
with endoscopic treatment showed that endoscopic treatment is not better than open surgery per se. Further research is needed in the area.
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The 30-day mortality rate after bile duct treatment in Denmark fell for
patients treated electively during the period studied.
12.8 T REATMENT OF PATIENTS WITH GALLSTONE PANCREATITIS
This group of patients cannot be identified with certainty in the National
Hospital Discharge Register, which is why no treatment rates are stated.
Due to the high risk of recurrence of pancreatitis (25-50%) treatment is
always indicated for this group of patients. The treatment technologies,
used are a) cholecystectomy (in the form of traditional open laparotomy,
minilaparotomy or laparoscopy) perhaps combined with open or endoscopic bile duct treatment, b) endoscopic operation perhaps followed by
simple cholecystectomy. The primary purpose of the treatment is to make
sure that the pancreatitis does not develop into a more serious condition.
The secondary purpose of the treatment is to remove the cause of the pancreatitis so the patient does not suffer a relapse.
The treatment depends on the severity of the pancreatitis. In mild
cases, the patient ought to be observed in hospital until the pancreatitis
subsides, after which a cholecystectomy or sphincterotomy should be performed. General agreement has not been reached about the initial treatment of severe pancreatitis, as three randomised studies showed that subacute sphincterotomy is best, while a fourth study showed the opposite.
All the materials were open to criticism, so new examinations are required. If a sphincterotomy is not performed sub-acutely on a patient with
severe pancreatitis, the patient ought to be observed and treated like a patient with mild pancreatitis.
If a sphincterotomy is performed on the patient there is no reason for
a routine cholecystectomy to be performed later.
12.9 T HE PATIENT
Post-operative pains, length of hospital stay, length of convalescence and
persistent pains are discussed under the individual technologies.
Gallstone patients’ choices of methods of treatment for stones in the
gallbladder and stones in the bile duct were not revealed by the literature.
One study of a group of patients without gallstones showed that more
would prefer ESWL instead of laparoscopic cholecystectomy, while both
these methods were deemed preferable to traditional open cholecystectomy. A single survey showed that patients expect a cholecystectomy to
cure 100% of their pains.
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According to Danish legislation, patients are entitled to information
about any serious complications associated with treatment. The literature
does not reveal the extent to which patients are informed about the risk of
complications.
International literature shows that patients are generally very satisfied
with cholecystectomy – regardless of the type of incision. More detailed
questions posed to patients after laparoscopic cholecystectomy showed
that the patients thought they were suffering more pains afterwards than
they had been led to expect.
Randomised studies of cholecystectomy by laparoscopy versus minilaparotomy show the same degree of patient satisfaction after a few months.
Significantly more patients were satisfied with their scar after 12 weeks in
the laparoscopy group (84%) than in the minilaparotomy group (74%).
A large proportion of patients thought that they were sent home too soon,
after laparoscopic as well as after traditional open cholecystectomy.
There is a clear need to study patient preferences after they have been
provided with in-depth information about the advantages and disadvantages of different methods of treatment.
12.10 T HE ORGANISATION
According to the Danish National Board of Health, cholecystectomy and
non-complicated bile duct surgery should be performed in all surgical departments, ERCP should be centred on one location per county, while
treatment of difficult bile duct stones and examination for and treatment
of biliary tract dyskinesia should be limited to specially selected departments throughout the country.
The number of surgical departments performing biliary tract surgery
fell from 75 in 1978-83 to 58 in 1992-95. During the latter period, an average of 81 operations was performed per department per year, varying
from 10 to over 100. The average number for simple cholecystectomy was
55 with a variation from under 10 to over 100 operations per annum. No
significant systematic relationship was identified between mortality and
the number of annual operations, but a tendency towards a higher 30-day
mortality rate was identified in the quarter of the hospitals in which the
highest number of operations were performed. On the other hand, the
quarter of departments that performed the fewest operations undertook
significantly more complicated courses of treatment than the quarter that
performed most operations. This assessment is unable to identify the
causes of these differences. As far open surgery is concerned, there is no
155
evidence to link the number of operations per surgeon with the number of
complications. On the other hand, the literature does suggest that complications after laparoscopic cholecystectomy fall according to the number of operations performed by the surgeon. The international literature
suggests that each surgeon has to perform 30-50 laparoscopic operations
before the complication level is brought down to a reasonably low level.
If these findings are transferred to Danish conditions, then only a few surgeons should perform the operations in order to maintain a low complication rate. Thus, it is necessary to centralise cholecystectomy operations
if the laparoscopic method is to be continued.
Performing ERCP also requires training and updates to a degree that
requires centralisation, something which is also recommended by the
Danish National Board of Health.
12.11 E CONOMY
The costs of biliary tract treatments can be divided into direct costs (the
stay in hospital, staff costs for the surgery plus the technological equipment), indirect expenses (sickness benefit) and intangible costs (fear, anxiety, etc). The latter category is not included in this assessment. The costs
of time spent in hospital, staff, technological equipment and sick leave are
calculated partly on the basis of a questionnaire survey sent to all surgical
and selected medical departments in Denmark and partly on the basis of
publicly available national data.
The direct costs for all biliary tract treatments in Denmark fell steadily
from 1978 to 1991, after which they rose slightly. Calculated as costs per
admission to hospital, they fell throughout the period, slightly more pronounced around the time of the introduction of laparoscopic cholecystectomy. For simple cholecystectomy, the fall in direct costs in the 80s was replaced by stagnation. The fall in the 80s was due to shorter stays in hospital, while the rise or stagnation in the 90s was due to a combination of
a continued reduction in the time spent in hospital combined with an increase in the number of patients treated and the use of more expensive
technology. This corresponds to the international literature.
The direct costs for a simple cholecystectomy without complications
were calculated at DKK 9,251 for a laparoscopic cholecystectomy, DKK
6,169 for a cholecystectomy by minilaparotomy and DKK 15,189 for a
traditional open cholecystectomy.
The costs and effects of the three methods of access for cholecystectomy were compared with the help of financial models (cost-effectiveness
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analyses). The analyses showed that cholecystectomy by minilaparotomy
is both cheaper and better than laparoscopic cholecystectomy. This fact is
consistent in sensitivity analyses in which conditions are varied. Only if
the difference in the length of the stay in hospital exceeds 2 days, does laparoscopic cholecystectomy become cheaper than cholecystectomy by
minilaparotomy. The annual costs for the current number of simple cholecystectomies would be reduced by just under DKK 8 million if laparoscopic cholecystectomy was replaced by cholecystectomy by minilaparotomy. Cholecystectomy by traditional open laparotomy is better (because
of fewer bile duct lesions), but also more expensive than laparoscopic
cholecystectomy. This fact was also consistent in the sensitivity analyses,
as only a significant reduction in the number of operations per annum
(less than 20) would make this method cheaper than laparoscopic cholecystectomy.
A financial model was drawn up regarding use of disposable versus
reusable equipment for laparoscopic cholecystectomy. The model showed
that reusable equipment was poorer as it resulted in a greater number of
conversions to open surgery but was also cheaper than disposable equipment. Again, this stood up well in sensitivity analyses. After account had
been taken of the higher number of conversions and longer operations,
longer stays in hospital and longer convalescence occasioned by the use of
reusable equipment, the annual costs would be approximately DKK 9 million less if reusable equipment was consistently used compared with consistent use of disposable equipment at current operation rates.
The literature also included financial comparisons between ESWL/bile
salts and cholecystectomy, which showed that laparoscopic cholecystectomy was more cost-efficient than ESWL/bile salts, which on the other
hand was slightly more cost-effectiveness than traditional open cholecystectomy. ESWL/bile salts were not compared with minilaparotomy.
As far as treatment of acute cholecystitis is concerned, sub-acute cholecystectomy is cheaper than performing an operation some months later.
As far as indications for bile duct stone examination during cholecystectomy are concerned, a cost-effectiveness analysis suggested that selective intraoperative cholangiography would be a better strategy than routine cholangiography.
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13. Synthesis and
recommendations
This chapter presents a synthesis based on the four standard elements in a
health technology assessment: the technology, the patient, the organisation and the finances; and considers what recommendations could be
based on the HTA analysis. The synthesis is marked by the fact that indepth analysis and extensive information about the technology and financial aspects of simple cholecystectomy are available, while information is scarce about the patient and organisation. The synthesis culminates
in a proposal for a new structure which ensures the future use of evidencebased practices in the treatment of patients with biliary tract disorders.
The report should be used by scientific societies and health authorities
in their attempts to define guidelines for diagnostics, prevention, treatment and care of patients with biliary tract disorders.
Prevention
Since the direct costs of biliary tract treatment in Denmark are approx.
DKK 120 million per annum, preventative options ought to be examined.
At the moment, there is a lot of focus on lifestyle in Denmark, e.g. fatty
food, lack of exercise, smoking and obesity as causes of cardiovascular
disease and cancer. Since gallstones are associated with these lifestyle factors, the attention paid to these areas may help reduce the incidence of
gallstones.
It is possible to reduce the risk of forming gallstones significantly by
taking bile salts during heavy weight loss. The clinical significance and financial consequences have, however, not been studied in sufficient depth.
Further research is necessary.
Secondary prevention in the form of prophylactic cholecystectomy
(cholecystectomy in people with gallstones without characteristic symptoms) cannot be recommended.
Pregnancy is the greatest single risk factor for gallstones in women. A
survey is recommended of the extent to which screening of pregnant
women and subsequent extracorporeal pulverisation and/or medicinal
dissolution of any newly-formed gallstones after the birth would be costefficient and acceptable to the patients.
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Uncomplicated gallbladder stones
The international literature and developments in cholecystectomy rates in
Denmark both point clearly to the fact that too many cholecystectomies
are performed. It is recommended that national guidelines be drawn up
for diagnostics and indications for treatment. It is recommended that the
departments which treat patients with gallstones draw up a system to ensure that the guidelines are adhered to. This could either take the form of
local audits at regular intervals or a computer programme containing data
from all gallstone patients. This would register the department’s practices
in relation to the guidelines. Since the natural history of gallstones is relatively peaceful, a conservative treatment strategy is justified.
The recommended standard treatment is cholecystectomy and the
choice is between three methods: laparoscopy, minilaparotomy or traditional open laparotomy:
❖
As far as the primary purpose of the treatment is concerned (absence of pain),
there are no differences between the three methods
❖
As far as the length of time spent in hospital and the length of the convalescence
are concerned, there is no difference between laparoscopy and minilaparotomy,
while traditional open laparotomy probably lengthens the time spent in hospital
and the convalescence period.
❖
The transition from traditional open laparotomy to the laparoscopic method caused an increase in bile ducts lesions. There is no evidence to suggest that cholecystectomy by minilaparotomy should lead to more bile duct lesions than laparoscopy - the literature points to the opposite, but the documentation is not solid. For
the time being, these two methods of access for cholecystectomy must be considered equal as far as bile duct lesions are concerned.
❖
The laparoscopic method is more expensive than minilaparotomy and the laparoscopic method requires longer training.
❖
No surveys have been conducted into patient preferences between the two
methods.
On the face of it, cholecystectomy by minilaparotomy seems to be a safe
and financially advantageous alternative to laparoscopic cholecystectomy.
If it is decided to continue using laparoscopic surgery, this HTA recommends that the operations are centralised in few locations. A debate
should be encouraged to assess the training requirements and population
base necessary to make sure that surgeons and their staff receive the nec-
159
essary training and routine in laparoscopic cholecystectomy. However, laparoscopic cholecystectomy and cholecystectomy by minilaparotomy are
not mutually self-exclusive. It is recommended that randomised trials be
conducted comparing the two methods and examining patient preferences.
A small group of patients experiences dysfunction of the bile duct
sphincter after cholecystectomy. It is recommended that national guidelines be drawn up for the examination and treatment of this condition.
Alternatives to cholecystectomy include the removal or dissolution of
gallbladder stones. These methods are used on patients who are too sick
to tolerate a general anaesthetic. The procedures can be performed under
local anaesthesia and, in certain cases, as medicinal treatment. It is recommended that guidelines be drawn up for which of the many methods
ought to be used as a matter of routine. Cholecystectomy is frequently accompanied by dyspepsia and pains, and in approximately half of the patients gallstones do not recur after dissolution or surgical removal. As a
result, a reassessment of the use of cholecystolithotomy or ESWL/bile salts
is recommended.
Some patients experience violent pains reminiscent of gallstone attacks
without having gallstones. No correct method of examination and treatment has been defined for this group of patients. It is recommended that
the group be examined in-depth in order to optimise treatment strategies.
Acute cholecystitis
It has been documented that the treatment of uncomplicated acute cholecystitis in the form of cholecystectomy not more than 7-10 days after initial symptoms is better than cholecystectomy after some months. If the
time limit of 7-10 days is exceeded, the operation ought, however, to wait
until the patient enters a calmer phase.
Ultrasonic drainage of the gallbladder may be sufficient treatment for
particularly ill people who cannot tolerate sub-acute operation. Any subsequent treatment for gallbladder stones ought to follow the same guidelines as treatment for uncomplicated gallbladder stones.
The extent to which ultrasonic drainage is necessary in patients due to
undergo a cholecystectomy has not been documented. Further research in
this field is recommended.
Stones in the bile ducts
Examination for stones in the bile ducts can be done by ERCP or MRC.
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The extent to which MRC provides sufficiently accurate diagnoses is unclear. It is recommended that this question be studied in greater depth
since MRC is non-invasive and, thus, does not entail the complications
caused by ERCP. Since the number of patients whose bile ducts are examined by means of ERCP has risen sharply, this HTA recommends that
guidelines be drawn up for when indications exist for examination of the
bile duct. Regular audits ought to be conducted to make sure that the
guidelines are adhered to.
It is well documented that there is no indication in favour of routine
examination of the bile duct for stones in connection with cholecystectomy; on the contrary, this gives rise to unnecessary treatment. The available literature and the data from the National Hospital Discharge Register suggest that a number of patients have their bile ducts examined unnecessarily. With simple methods, it is possible before an operation is performed to identify the patients who need to be examined. It is recommended that guidelines be drawn up for when the bile duct should be examined in connection with cholecystectomy and that regular audits be
conducted to make sure that the guidelines are adhered to.
The recommended treatment of symptomatic stones in the bile duct is
sub-acute ERCP with sphincterotomy and extraction of the stones. The
literature suggests that this is the correct treatment if the patient also suffers from cholangitis (infection of the bile ducts). For the time being, this
ought to be the treatment for patients with bile duct stones without
cholangitis as well, but the results of a number of randomised trials suggest that the use of open surgery ought to be reassessed. It is recommended
that this reassessment take the form of randomised trials.
Very few patients who have stones removed from their bile duct by endoscopy experience later symptoms from stones in the gallbladder. As a
result, routine cholecystectomy for patients after successful removal of
stones is not recommended.
The introduction of laparoscopy in Denmark for removal of stones
from the bile ducts cannot be recommended on the basis of the current literature.
A whole series of technologies have been developed for the removal of
complicated bile duct stones. It is recommended that the relevant technologies be studied in order to decide which ones should be used in Denmark and to devise the correct organisational structure for their use. The
necessary patient base and degree of centralisation ought to be discussed.
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Gallstone pancreatitis
It has been documented that patients admitted with gallstone pancreatitis
run a great risk of recurrence and, therefore, should receive treatment designed to prevent any relapse before they are discharged from hospital.
Initially, conservative treatment is recommended for patients with less
severe cases of gallstone pancreatitis, but their condition should be monitored in case it deteriorates. Before discharge – but not until after the pancreatitis has subsided – the patient ought to be offered a cholecystectomy.
If the patient is unable to tolerate surgery, endoscopic sphincterotomy
should be offered instead.
If a patient with gallstone pancreatitis also exhibits signs of obstruction
of the bile duct or cholangitis, a sub-acute sphincterotomy ought to be
performed.
The international literature about patients with severe gallstone pancreatitis reveals diverging opinions about the initial treatment, which can
either be conservative or take the form of a sub-acute sphincterotomy. It is
recommended that a randomised trial look into this difference of opinion.
If a sphincterotomy is performed on a patient with gallstone pancreatitis, the only reason for subsequent cholecystectomy is if the patient gets
symptoms of, or complications to, gallbladder stones.
Proposals for the quality control of treatment of patients with biliary
tract disorders in Denmark
Technology for the treatment of patients with gallstones will probably
continue to develop. To make sure that future treatment of biliary tract
disorders in Denmark is evidence-based – involving all four elements of a
health technology assessment – it would be appropriate to structure the
work and introduce continuous quality control. A plan of action for quality control could, for example, include the following:
162
❖
Establishment of a national database of all diagnoses and treatments of biliary
tract disorders. It should be managed and operated by professional groups with
insight into the four elements in a health technology assessment. Funds should be
procured for the continuous operation and use of the database.
❖
Establishment of a mechanism to ensure that new literature is read and assessed
according to explicit criteria. This work should be co-ordinated with the hepatobiliary group in the Cochrane Collaboration.
❖
Initiation and co-ordination of randomised trials into different diagnostic, preventative, therapeutic and care options. .
❖ Establishment of local quality control systems.
Until an acceptable quality control system has been established, it is recommended that developments in the treatment of biliary tract disorders be
followed in the National Hospital Discharge Register and according to the
methods applied in this report.
The relevant scientific societies ought to collaborate with the Danish
National Board of Health to reassess the need for training in biliary tract
treatments – especially the number of specialists who need to be trained in
the different functions. In this context, the establishment of one or more
centres for biliary tract treatment might be considered.
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Appendix 1.
Literature list
The Literature is in alphabetic order, except the last seven references.
164
1.
Abboud PA, Malet PF, Berlin JA, et al. Predictors of common bile duct stones prior to cholecystectomy: a meta-analysis.
Gastrointest Endosc 1996; 44:450-5.
2.
Achord JL. Are all gallstones “silent” until acute cholecystitis occurs? Gastroenterology 1989; 97:1591-2.
3.
Ackland MJ, Jolley DJ, Ansari MZ. Postoperative complications of cholecystectomy in Victorian public hospitals. Aust N Z J
Public Health 1996; 20:583-8.
4.
Acosta JM, Ledesma CL. Gallstone migration as a cause of acute pancreatitis. N Engl J Med 1974;290:484-7.
5.
Acosta JM, Rossi R, Galli OMR, Pellegrini CA, Skinner DB. Early surgery for acute gallstone pancreatitis: Evaluation of a
systematic approach. Surgery 1978;83:367-70.
6.
Adam A, Roddie ME. Acute cholecystitis: radiological management. Baillieres Clin Gastroenterol 1991; 5:787-816.
7.
Adamek HE, Maier M, Jakobs R, Wessbecher FR, Neuhauser T, Riemann JF. Management of retained bile duct stones:
a prospective open trial comparing extracorporeal and intracorporeal lithotripsy. Gastrointest Endosc 1996; 44:40-7.
8.
Adamek HE, Sorg S, Bachor OA, Riemann JF. Symptoms of post-extracorporeal shock wave lithotripsy: long-term analysis of
gallstone patients before and after successful shock wave lithotripsy. Am J Gastroenterol 1995; 90:1125-9.
9.
Adams WJ, Avramovic J, Barraclough BH. Wound infiltration with 0.25% bupivacaine not effective for postoperative
analgesia after cholecystectomy. Aust N Z J Surg 1991; 61:626-30.
10.
Adamsen S, Hansen OH, Funch Jensen P, Schulze S, Stage JG, Wara P. Bile duct injury during laparoscopic cholecystectomy:
a prospective nationwide series. J Am Coll Surg 1997; 184:571-8.
11.
Adamsen S, Hansen OH, Funch Jensen P, Schulze S, Stage JG, Wara P, Jensen LP. Laparoskopisk kolecystektomi i Danmark.
En prospektiv registrering. Ugeskr Læg 1995;157:4449-54.
12.
Agnifili A, Ibi I, Guadagni S, et al.Perioperative pain and stress: a comparison between video laparoscopic cholecystectomy
and “open” cholecystectomy. G Chir 1993; 14:344-8.
13.
Aguilar JL, Montes A, Montero A, Vidal F, F Llamazares J, Pastor C. Continuous pleural infusion of bupivacaine offers better
postoperative pain relief than does bolus administration. Reg Anesth 1992; 17:12-4.
14.
Airan M, Appel M, Berci G et al. Retrospective and prospective multi-institutional laparoscopic cholecystectomy study
organized by the Society of American Gastrointestinal Endoscopic Surgeons. Surg Endosc 1992;6:169-76.
15.
Airan MC, Ko ST. Assessment of quality of care in laparoscopic cholecystectomy. Am Coll Med Qual 1992;7:85-7.
16.
Akiyama H, Nagusa Y, Fujita T. A new method for non-surgical cholecystolithotomy. Surg Gyn Obst 1985;161:77-4
17.
Akiyama H, Okazaki T, Takashima I, et al. Percutaneous treatments for biliary diseases. Radiology 1990; 176:25-30.
18.
Akriviadis EA, Hatzigavriel M, Kapnias D, Kirimlidis J, Markantas A, Garyfallos A. Treatment of biliary colic with diclofenac:
a randomized, double-blind, placebo-controlled study. Gastroenterology 1997; 113:225-31.
19.
Alexander DJ, Ngoi SS, Lee L, et al. Randomized trial of periportal peritoneal bupivacaine for pain relief after laparoscopic
cholecystectomy. Br J Surg 1996; 83:1223-5.
20.
Ali J, Khan TA. The comparative effects of muscle transection and median upper abdominal incisions on postoperative
pulmonary function. Surg Gyn Obst 1979;148:863-6.
21.
Alinder G, Nilsson U, Lunderquist A, Herlin P, Holmin T. Pre-operative infusion cholangiography compared to routine
operative cholangiography at elective cholecystectomy. Br J Surg 1986;73:383-7.
22.
Allen MJ, Borody TJ, Bugliosi TF, May GR, LaRusso NF, Thistle JL. Rapid dissolution of gallstones by methyl tert-butyl ether.
N Eng J Med 1985;312:217-20.
23.
Amaral JF. Laparoscopic cholecystectomy in 200 consecutive patients using an ultrasonically activated scalpel. Surg
Laparosc Endosc 1995; 5:255-62.
24.
Amstrup JH, Eldrup J, Wille-Jørgensen PA. Ekstrakorporal shockbølgelitotripsi ved behandling af sten i ductus choledochus.
Ugeskr Læg 1995;157:2143-6.
25.
Andersen OP, Hansen GL. Galdestenskirurgiens historie. Med Forum 1985;38:161-4.
26.
Anderson RE, Hunter JG. Laparoscopic cholecystectomy is less expensive than open cholecystecto-my. Surg Laparosc
Endosc 1991; 1:82-4.
27.
Andersson A, Bergdahl L. Disease of the gallbladder in patients with normal cholecystograms. Am J Surg 1976;132:322-4.
28.
Andersson A, Bergdahl L, Boquist L. Acalculous cholecystitis. Am J Surg 1971;122:3-7
29.
Andrén-Sandberg Å, Alinder G, Bengmark S. Accidential lesions of the common bile duct at cholecystectomy. Ann Surg
1985;201:328-32.
30.
Anonym. Stötvågsbehandling af njursten och gallsten. Statens Beredning för Utvärdering av medicisnk teknologi. SBU 1990.
31.
Anonym. Ekstrakorporal galdestensknusning. En præliminær rapport. Hvidovre Hospitals galdestens-gruppe. Ugeskr Læg
1991;153:332-5.
32.
Anonym. Sundhedsstyrelsen. Evaluering af Landspatientregisteret 1990. Sygehusstatistik 1993;II:57.
33.
Anonym. Indikationer og henvisningspraksis. Sundhedsstyrelsen 1995.
34.
Anonym. National strategi for medicinsk teknologivurdering. Sundhedsstyrelsen 1996.
35.
Anonym. Målbeskrivelse for speciallægeuddannelsen i kirurgi. Sundhedsstyrelsen, marts 1996.
36.
Anonym. Specialeplanlægning og lands- og landsdelsfunktioner i sygehusvæsenet. Vejledning. Sundhedsstyrelsen 1996.
37.
Anonym. Kikkertkirurgi i bughulen. Rapport fra en konsensus-konference 3.-5- marts 1997, København. DSI 1997.
ISBN 87-7488-332-1.
38.
Anonym. Vejledning om information og samtykke og om videregivelse af helbredsoplysninger mv. Bekendtgørelse om information og samtykke og om videregivelse af helbredsoplysninger mv. Lov om patientrs retsstilling. Sundhedsstyrelsen
1998.
39.
Anonymous. (GREPCO) Prevalence of gallstone disease in an Italian adult female population. Am J Epidemiol 1984;119:
796-805.
40.
Anonymous. Epidemiology of gallstone disease in Italy: comparison between a rural and urban female population. DISCO &
GREPCO. Ital J Gastroenterology 1987;19:129-33.
41.
Anonymous. (GREPCO) The epidemiology of gallstone disease in Rome, Italy. Part I. Prevalence data in men. Hepatology
1988;8:904-6.
42.
Anonymous. (GREPCO) The epidemiology of gallstone disease in Rome, Italy. Part II. Factors associated with the disease.
Hepatology 1988;8:907-13.
43.
Anonymous. A prospective analysis of 1518 laparoscopic cholecystectomies. The Southern Surgeons Club published
erratum appears in N Engl J Med 1991 Nov 21;325(21):1517-8 see comments. N Engl J Med 1991; 324:1073-8.
44.
Anonymous. Guidelines for the treatment of gallstones. American College of Physicians. Ann Int med 1993;119:620-2.
45.
Anonymous. NIH consensus conference. Gallstones and laparoscopic cholecystectomy. JAMA 1993;269:1018-24.
165
166
46.
Anonymous. The E.A.E.S. consensus development conference on laparoscopic cholecystectomy, appendectomy, and hernia
repair. Surg Endosc 1995;9:550-63.
47.
Anonymous. Bile acid therapy versus placebo before and after extracorporeal shock wave lithotripsy of gallbladder stones.
The East-Danish Gallstone Study Group. Aliment Pharmacol Ther 1996; 10:651-7.
48.
Anselmi M, Milos C, Schultz H, Munoz MA, Alvarez R, Maturana J. Effect of cholelithiasis and cholecystectomy on
duodenogastric biliary reflux. Rev Med Chil 1993; 121:1118-22.
49.
Armstrong PJ, Burgess RW. Choice of incision and pain following gallbladder surgery. Br J Surg 1990;77:746-8.
50.
Asbun HJ, Reddick EJ. Credentialing in laparoscopic surgery: a survey of physicians. J Laparoendosc Surg 1992; 2:27-32.
51.
Assalia A, Schein M, Kopelman D, Hashmonai M. Minicholecystectomy vs conventional cholecystecto-my: a prospective
randomized trial – implications in the laparoscopic era. World J Surg 1993; 17:755-9.
52.
Assouline Y, Liguory C, Ink O, et al. Current results of endoscopic sphincterotomy for lithiasis of the common bile duct.
Gastroenterol Clin Biol 1993; 17:251-8.
53.
Attili AF, Carulli N, Roda E, et al. Epidemiology of gallstone disease in Italy: prevalence data of the Multicenter Italian Study on
Cholelithiasis (M.I.COL.). Am J Epidemiol 1995; 141:158-65.
54.
Attili AF, De Santis A, Capri R, Repice AM, Maselli S. The natural history of gallstones: the GREPCO experience. The GREPCO
Group. Hepatology 1995; 21:655-60.
55.
Azurin DJ, Go LS, Maslack M, Kirkland ML. Bile leak following laparoscopic cholecystectomy. J Laparoendosc Surg
1995;5:233-6.
56.
Bailey RW, Zucker KA, Flowers JL, Scovill WA, Graham SM, Imbembo AL. Laparoscopic cholecystectomy. Experience with
375 consecutive patients. Ann Surg 1991; 214:531-40.
57.
Bainton D, Davies GT, Evans KT, Gravelle IH. Gallbladder disease. Prevalence in a South Wales industrial town. N Engl J Med
1976;294:1147-9.
58.
Baird DR, Wilson JP, Mason EM, et al. An early review of 800 laparoscopic cholecystectomies at a university-affiliated
community teaching hospital. Am Surg 1992; 58:206-10.
59.
Bar-Meir S, Halpern Z, Bardan E, Gilat T. Frequency of papillary dysfunction among cholecystectomi-zed patients.
Hepatology 1984;4:328-30.
60.
Bar-Meir S, Halpern Z, Bardan E. Nitrate therapy in a patient with papillary dysfunction. Am J Gastroenterol 1983;78:94-5.
61.
Barbara L, Festi D Morselli Labate AM, Roda E, Rusticali AG, Sama C, Sapio C, Taroni F. The Sirmione study: Familial frequency
of gallstone disease. Hepatology 1984;4:1086.
62.
Barbara L, Sama C, Labate AMM, Taroni F, Rusticali AG, Festi D, Sapio C, Roda E, Banterle C, Puci A, Formentini F, Colasanti S,
Nardin F. A population study on the prevalence of gallstone disease: The Sirmione study. Hepatology 1987;7:913-7.
63.
Bardram L, Jacobsen B, Jensen PMF, Edvardsen L. Lokalt kursus i konventionel og laparoskopisk kirurgisk teknik. Ugeskr Læg
1995;157:5845.
64.
Barkun AN, Barkun JS, Sampalis JS, and the McGill gallstone treatment trial group. Gallbladder stone shock wave litotripsy
vs. laparoscopic cholecystectomy. A randomized clinical trial. Clin Invest Med 1992;15(suppl):A44 (Abstract).
65.
Barkun JS, Barkun AN, Sampalis JS, et al. Randomised controlled trial of laparoscopic versus mini cholecystectomy.
The McGill Gallstone Treatment Group see comments. Lancet 1992; 340:1116-9.
66.
Barteau JA, Castro D, Arregui ME, Tetik C. A comparison of intraoperative ultrasound versus cholangiography in the
evaluation of the common bile duct during laparoscopic cholecystectomy. Surg Endosc 1995; 9:490-6.
67.
Bass EB, Pitt HA, Lillemoe KD. Cost-effectiveness of laparoscopic cholecystectomy versus open cholecystectomy. Am J Surg
1993; 165:466-71.
68.
Bass EB, Steinberg EP, Pitt HA, et al. Comparison of the rating scale and the standard gamble in measuring patient
preferences for outcomes of gallstone disease [see comments]. Med Decis Making 1994; 14:307-14.
69.
Bass EB, Steinberg EP, Pitt HA, et al. Cost-effectiveness of extracorporeal shock-wave lithotripsy versus cholecystectomy for
symptomatic gallstones. Gastroenterology 1991; 101:189-99.
70.
Bates T, Ebbs SR, Harrison M, A’Hern RP. Influence of cholecystectomy on symptoms. Br J Surg 1991; 78:964-7.
71.
Bateson M. Second opinions in laparoscopic cholecystectomy [see comments]. Lancet 1994; 344:76
72.
Battersby C, Askew A. Experience with biliary audit [see comments]. Aust N Z J Surg 1991; 61:570-5.
73.
Beal JM. Historical perspectives of gallstone disease. Surg Gyn Obst 1984;158:181-9.
74.
Bell RC, Van Stiegmann G, Goff J, Reveille M, Norton L, Pearlman NW. Decision for surgical management of perforation
following endoscopic sphincterotomy. Am Surg 1991; 57:237-40.
75.
Bellon JM, Manzano L, Bernardos L, et al. Cytokine levels after open and laparoscopic cholecystecto-my. Eur Surg Res 1997;
29:27-34.
76.
Berci G, Morgenstern L. Laparoscopic management of common bile duct stones. A multi-institutional SAGES study. Society
of American Gastrointestinal Endoscopic Surgeons see comments. Surg Endosc 1994; 8:1168-74.
77.
Berci G, Sackier JM, Paz Partlow M. Routine or selected intraoperative cholangiography during laparoscopic
cholecystectomy? Am J Surg 1991; 161:355-60.
78.
Berger H, Leibl A, Kohz P, Briegel T, Pratschke E. [The results of a long-term follow-up of patients with a percutaneous
cholecystostomy]. Rofo Fortschr Geb Rontgenstr Neuen Bildgeb Verfahr 1993; 159:518-21.
79.
Berggren U, Gordh T, Grama D, Haglund U, Rastad J, Arvidsson D. Laparoscopic versus open cholecystectomy:
hospitalization, sick leave, analgesia and trauma responses see comments. Br J Surg 1994; 81:1362-5.
80.
Berggren U, Zethraeus N, Arvidsson D, Haglund U, Jonsson B. A cost-minimization analysis of laparoscopic cholecystectomy
versus open cholecystectomy. Am J Surg 1996; 172:305-10.
81.
Bergman JJ, Rauws EA, Fockens P, et al. Randomised trial of endoscopic balloon dilation versus endoscopic sphincterotomy
for removal of bileduct stones see comments. Lancet 1997; 349:1124-9.
82.
Bernard HR, Hartman TW. Complications after laparoscopic cholecystectomy. Am J Surg 1993; 165:533-5.
83.
Berndt H, Nurnberg D, Pannwitz H. Prevalence of cholelithiasis. Results of an epidemiologic study using sonography in East
Germany. Z Gastroenterol 1989; 27:662-6.
84.
Bero L, Rennie D. The Cochrane Collaboration. Preparing, maintaining, and disseminating systematic reviews of the effects of
health care. JAMA 1995;274:1935-8.
85.
Bickerstaff KI, Berry AR, Chapman RW, Britton J. Endoscopic sphincterotomy for bile duct stones: an institutional review of
272 patients. Ann R Coll Surg Engl 1989; 71:384-6.
86.
Bielik J. Asymptomatic cholecystolithiasis in an ultrasonographic investigation in Trencín. Vnitrní Lékarství 1992;38:378-83
87.
Bing Z et al. Percutaneous cholecystolithocenosis: Report og 421 cases. Chinese J Surg 1991;29:350-6.
88.
Birdi I, Hunt TM, Veitch PS, Armon M, Jervis P, Barr C. Laparoscopic cholecystectomy in Leicester: an audit of 555 patients.
Ann R Coll Surg Engl 1994; 76:390-5.
89.
Bittner R, Leibl B, Kraft K, Butters M, Nick G, Ulrich M. Laparoscopic cholecystectomy in therapy of acute cholecystitis:
immediate versus interval operation. Chirurg 1997; 68:237-43.
90.
Bjerkeset T, Edna TH, Drogset JO, Svinsas M. Early elective cholecystectomy in acute stone-related cholecystitis. Tidsskr Nor
Laegeforen 1997; 117:2941-3.
91.
Bjerkeset T, Drogset JO, Svinsas M. Kan dødeligheten ved gallsteinssykdom reduseres? Tidsskr Nor Laegeforen 1997;
117:2944-6.
92.
Black NA, Thompson E, Sanderson CF. Symptoms and health status before and six weeks after open cholecystectomy:
a European cohort study.ECHSS Group. European Collaborative Health Services Study Group. Gut 1994; 35:1301-5.
167
93.
Blackford SD, Bird RM, Casscells SW. Non-operative results in ninety patients with abnormal cholecystograms. Ann Int Med
1942;16:1118-22.
94.
Blake DW, Donnan G, Novella J. Interpleural administration of bupivacaine after cholecystectomy: a comparison with
intercostal nerve block. Anaesth Intensive Care 1989; 17:269-74.
95.
Blamey SL, Imrie CW, O’Neill J, Gilmour WH, Carter DC. Prognostic factors in acute pancreatitis. Gut 1984;25:1340-6.
96.
Bodvall B, Övergaard B. Computer analysis of postcholecystectomy biliary tract symptoms. Surg Gyn Obstet 1967;124:
723-32.
97.
Boender J, Nix GA, de Ridder MA, et al. Endoscopic papillotomy for common bile duct stones: factors influencing the
complication rate. Endoscopy 1994; 26:209-16.
98.
Bond G, De Costa A. Laparoscopic cholecystectomy: the experience of community hospital. Aust N Z J Surg 1996; 66:14-7.
99.
Bongard FS, Pianim NA, Leighton TA, Dubecz S, Davis IP, Lippmann M, Klein S, Liu S-Y. Helium insufflation for laparoscopic
operation. Surg Gyn Obst 1993;177:140-6.
100. Bordelon BM, Hobday KA, Hunter JG. Incision extension is the optimal method of difficult gallbladder extraction at
laparoscopic cholecystectomy. Surg Endosc 1992; 6:225-7.
101. Botoman VA, Kozarek RA, Novell LA, et al. Long-term outcome after endoscopic sphincterotomy in patients with biliary
colic and suspected sphincter of Oddi dysfunction. Gastrointest Endosc 1994; 40:165-70.
102.
Bouhaddou O, Frucci L, Cofrin K, et al. Implementation of practice guidelines in a clinical setting using a computerized
knowledge base (Iliad). Proc Annu Symp Comput Appl Med Care 1993; 258-62.
103. Bourke JB, Lear PA, Taylor M. Effect of early return after elective repair of inguinal hernia: Clinical and financial consequences
at one year and three years. Lancet 1981;II:623-5
104. Bozkurt T, Orth KH, Butsch B, Lux G. Long-term clinical outcome of post-cholecystectomy patients with biliary-type pain:
results of manometry, non-invasive techniques and endoscopic sphincterotomy. Eur J Gastroenterol Hepatol 1996; 8:245-9.
105. Bradbury AW, Stonebridge PA, Wallace IW, Macleod DA, Rainey JB. Open biliary surgery and the use of routine inpatient
audit. J R Coll Surg Edinb 1993; 38:86-8.
106. Bredesen J, Jorgensen T, Andersen TF, et al. Early postoperative mortality following cholecystectomy in the entire female
population of Denmark, 1977-1981. World J Surg 1992; 16:530-5.
107. Bremner DN, McCormick JSC, Thomson JWW, McNair TJ. A study of cholecystectomy. Surg Gyn Obst 1974;138:752-4.
108. Breslin AB, Wadhwa V. Cholelithoptysis: a rare complication of laparoscopic cholecystectomy. Med J Aust 1996; 165:373-4.
109. Breslow N, Claiton D. Approximate inference in generalized linear mixed models. J Am Statist Ass 1993;88:9-25.
110. Brett M, Barker JP. The world distribution of gallstones. Int J Epidemiol 1976;5:335-41.
111. Brodish RJ, Fink AS. ERCP, cholangiography, and laparoscopic cholecystectomy. The Society of American Gastrointestinal
Endoscopic Surgeons (SAGES) opinion survey. Surg Endosc 1993; 7:3-8.
112. Browning PD, McGahan JP, Gerscovich EO. Percutaneous cholecystostomy for suspected acute cholecystitis in the
hospitalized patient. J Vasc Interv Radiol 1993; 4:531-7.
113. Bruhn EW, Miller FJ, Hunter JG. Routine fluoroscopic cholangiography during laparoscopic cholecystectomy: an argument.
Surg Endosc 1991; 5:111-5.
114. Brune IB, Schonleben K, Omran S. Complications after laparoscopic and conventional cholecystectomy: a comparative study.
HPB Surg 1994; 8:19-25.
115. Buanes T, Mjaland O. Complications in laparoscopic and open cholecystectomy: a prospective comparative trial. Surg
Laparosc Endosc 1996;6:266-72.
116. Buanes T, Mjaland O, Waage A, Solheim K, Faerden AE. A national registry for cholecystectomy. Quality assurance with
practical consequences? Landsregister for kolecystektomi. Kvalitetssikringstil-tak med praktiske konsekvenser. Tidsskr Nor
Laegeforen 1995; 115:2236-9.
168
117. Buhler L, Mentha G, Borst F, Roche B, Morel P, Rohner A. [Safety of cholecystectomy by laparotomy in elective situation and
in emergency]. J Chir Paris 1992; 129:466-70.
118. Burhenne HJ, Stoller JL. Minicholecystectomy and radiologic stone extraction in high-risk cholelithiasis patients. Am J Surg
1985;149:632-5.
119. Burnett W, Shield R. Symptoms after cholecystektomy. Lancet 1958;i:923-5.
120. Burnett W. The management of acute cholecystitis. Aust NZ J Surg 1971;41:25.
121. Burnstein MJ, Vassal KP, Strasberg SM. Results of Combined drainage and cholecystokinin cholecystography in 81 patients
with normal oral cholecystogram. Ann Surg 1982;196:627-32.
122. Byl B, Deviere J, Struelens MJ, et al. Antibiotic prophylaxis for infectious complications after therapeutic endoscopic retrograde cholangiopancreatography: a randomized, double-blind, placebo-controlled study. Clin Infect Dis 1995; 20:1236-40.
123. Cabrera JC, Matute E, Escolano F, Castillo J, Santiveri X, Castano J. [Efficacy of ondansetron in the prevention of nausea and
vomiting after laparoscopic cholecystectomy]. Rev Esp Anestesiol Reanim 1997; 44:36-8.
124. Cabrol J, Navarro X, Simo Deu J, Segura R. Evaluation of duodenogastric reflux in gallstone disease before and after simple
cholecystectomy. Am J Surg 1990; 160:283-6.
125. Cairns SR, Dias L, Cotton PB, Salmon PR, Russell RC. Additional endoscopic procedures instead of urgent surgery for retained
common bile duct stones. Gut 1989; 30:535-40.
126. Caputo L, Aitken DR, Mackett MC, Robles AE. Iatrogenic bile duct injuries. The real incidence and contributing factors
implications for laparoscopic cholecystectomy. Am Surg 1992; 58:766-71.
127. Carlson GL, Rhodes M, Stock S, Lendrum R, Lavelle MI, Venables CW. Role of endoscopic retrograde
cholangiopancreatography in the investigation of pain after cholecystectomy. Br J Surg 1992; 79:1342-5.
128. Carlsson P. Minskar gallstenssjukdomarna i samhället? Nord Med 1984;99:170-3.
129. Carroll BJ, Friedman RL, Liberman MA, Phillips EH. Routine cholangiography reduces sequelae of common bile duct
injuries. Surg Endosc 1996; 10:1194-7.
130. Cason CL, Seidel SL, Bushmiaer M. Recovery from laparoscopic cholecystectomy procedures. AORN J 1996; 63:
1099-103,1106-8,1111-2.
131. Catalano O, Lapiccirella G, Rotondo A. Papillary injuries and duodenal perforation during endoscopic retrograde
sphincterotomy (ERS): radiological findings. Clin Radiol 1997; 52:688-91.
132. Chaudhary A, Khanna R, Salunkhe S, Kapoor R, Sachdev A, Aranya RC. Tubeless, drainless, short-stay cholecystectomy.
Indian J Gastroenterol 1992; 11:9-10.
133. Chaussy CG, Brendel W, Schmiedt E. Extracorporeally induced destruction of kidney stones by shockwaves. Lancet
1980;2:1265-8.
134. Chen MF, Wang CS. A prospective study of the effect of cholecystectomy on duodenogastric reflux in humans using 24 hour
gastric hydrogen monitoring. Surg Gynecol Obstet 1992; 175:52-6.
135.
Chen XR, Lou D, Li SH, et al. Avoiding serious complications in laparoscopic cholecystectomy – lessons learned from an
experience of 2428 cases. Ann Acad Med Singapore 1996; 25:635-9.
136. Chen YK, Foliente RL, Santoro MJ, Walter MH, Collen MJ. Endoscopic sphincterotomy-induced pancreatitis: increased risk
associated with nondilated bile ducts and sphincter of Oddi dysfunction [see comments]. Am J Gastroenterol 1994; 89:32733.
137. Cheslyn-Curtis S, Emberton M, Ahmed H, Williamson RCN, Habib NA. Bile duct injury following laparoscopic
cholecystectomy. Br J Surg 1992;79:231-2.
138. Cheslyn Curtis S, Gillams AR, Russell RC, et al. Selection, management, and early outcome of 113 patients with
symptomatic gall stones treated by percutaneous cholecystolithotomy. Gut 1992; 33:1253-9.
139. Chia JK, Ross M. Gallstones exiting the urinary bladder: a complication of laparoscopic cholecystectomy letter. Arch Surg
1995; 130:677
169
140. Chiverton SG, Inglis JA, Hudd C, Kellett MJ, Russell RC, Wickham JE. Percutaneous cholecystolithotomy: the first 60 patients
see comments. BMJ 1990; 300:1310-2.
141. Chundrigar T, Hedges AR, Morris R, Stamatakis JD. Intraperitoneal bupivacaine for effective pain relief after laparoscopic
cholecystectomy. Ann R Coll Surg Engl 1993; 75:437-9.
142. Chung SC, Leung JW, Leong HT, Li AK. Mechanical lithotripsy of large common bile duct stones using a basket. Br J Surg
1991; 78:1448-50.
143. Classen M, Demling L. Endoscopische sphinkterotomie der papilla vateri. Dsch Med Wochenschr 1974;99:496-7.
144.
Classen M, Ossenberg W, Wurbs D, Dammerman R, Hagenmuller. Pancreatitis: An indication for endoscopic papillotomy?
Endoscopy 1978;10:223.
145. Clavien PA, Sanabria JR, Mentha G, et al. Recent results of elective open cholecystectomy in a North American and a
European center. Comparison of complications and risk factors see comments. Ann Surg 1992; 216:618-26.
146.
Cobb AB, Sanchez N, Miller D. Gallbladder surgery for Medicare patients in Mississippi. J Miss State Med Assoc 1994;
35:293-7.
147. Cocks J, Johnson W, Cade R, et al. Bile duct injury during laparoscopic cholecystectomy: a report of the Standards Subcommittee of the Victorian State Committee of the Royal Australasian College of Surgeons see comments. Aust N Z J Surg
1993; 63:682-3.
148. Coelho JC, de Araujo RP, Marchesini JB, Coelho IC, de Araujo LR. Pulmonary function after cholecystectomy performed
through Kocher’s incision, a mini-incision, and laparoscopy. World J Surg 1993; 17:544-6.
149. Cohen MM, Young W, Theriault ME, Hernandez R. Has laparoscopic cholecystectomy changed patterns of practice and
patient outcome in Ontario? Can Med Assoc J 1996; 154:491-500.
150. Collet D. Laparoscopic cholecystectomy in 1994. Results of a prospective survey conducted by. Surg Endosc 1997; 11:56-63.
151. Collet D. Celioscopic cholecystectomy. A survey of the French Society of Endoscopic Surgery and Operative Radiology.
Apropos of 937 cases. Gastroenterol Clin Biol 1992; 16:302-8.
152.
Comfort MW, Gray HK, Wilson JM. The silent gallstone: A ten to twenty year follow-up study of 112 cases. Ann Surg
1948;128:931-7.
153. Cook J, Richardson J, Street A. A cost utility analysis of treatment options for gallstone disease: methodological issues and
results. Health Econ 1994; 3:157-68.
154. Coppola R, Riccioni ME, Ciletti S, et al. Analysis of complications of endoscopic sphincterotomy for biliary stones in a
consecutive series of 546 patients. Surg Endosc 1997; 11:129-32.
155. Corbitt JD, Jr. Laparoscopic cholecystectomy: laser versus electrosurgery [see comments]. Surg Laparosc Endosc 1991;
1:85-8.
156. Cotton PB, Kozarek RA, Schapiro RH, et al. Endoscopic laser lithotripsy of large bile duct stones. Gastroenterology 1990;
99:1128-33.
157.
Courtois CS, Picus DD, Hicks ME, et al. Percutaneous gallstone removal: long-term follow-up. J Vasc Interv Radiol 1996;
7:229-34.
158. Covarrubias C, Valdivieso V, Nervi F. Epidemiology of gallstone disease in Chile. I: Cappocaccia L, Ricci G, Angelico F et al, eds.
Epidemiology and prevention of gallstone disease. Lancaster: MTP Press Limited, 1984:26-30.
159. Cox MR, Gunn IF, Eastman MC, Hunt RF, Heinz AW. Open cholecystectomy: a control group for comparison with laparoscopic
cholecystectomy. Aust N Z J Surg 1992; 62:795-801.
160. Cox MR, Wilson TG, Luck AJ, Jeans PL, Padbury RT, Toouli J. Laparoscopic cholecystectomy for acute inflammation of the
gallbladder see comments. Ann Surg 1993; 218:630-4.
161. Cozzolino HJ, Goldstein F, Greening RR, Wirtz CW. The cystic duct syndrome JAMA 1974;185:920-4.
162. Croce E, Azzola M, Golia M, Russo R, Pompa C. Laparocholecystectomy. 6,865 cases from Italian institutions. Surg Endosc
1994; 8:1088-91.
170
163.
Csendes A, Diaz JC, Burdiles P, Maluenda F. Late results of immediate primary end to end repair in accidental section of the
common bile duct. Surg Gynecol Obstet 1989; 168:125-30.
164. Cucchiaro G, Rossitch JC, Bowie J, et al. Clinical significance of ultrasonographically detected coincidental gallstones. Dig Dis
Sci 1990; 35:417-21.
165.
Cuschieri A. The laparoscopic revolution – walk carefully before we run [editorial] [see comment]. J R Coll Surg Edinb 1989;
34:295
166. Cuschieri A, Berci G, McSherry CK. Laparoscopic cholecystectomy editorial. Am J Surg 1990; 159:273
167. Cuschieri A, Croce E, Faggioni A, et al. EAES ductal stone study. Preliminary findings of multi-center prospective randomized
trial comparing two-stage vs single-stage management see comments. Surg Endosc 1996; 10:1130-5.
168. Cuschieri A, Dubois F, Mouiel J, et al. The European experience with laparoscopic cholecystectomy. Am J Surg 1991;
161:385-7.
169. Cutter IS. John Stough Bobbs and lithotomy of the gallbladder. Int Abst Surg 1928;47:409-11.
170. Dallemagne B, Weerts JM, Jehaes C, Markiewicz S, Lombard R. [Cholecystectomy using celioscopy: analysis of 368
operations]. Acta Gastroenterol Belg 1992; 55:4-10.
171. Danzinger RG, Hofmann AF, Schoenfield LJ, Thistle JL. Dissolution of cholesterol gallstones by chenodeoxycholic acid. N Engl
J Med 1972;286:1-8.
172. Darzi A, Sheehan SS, Geraghty JG, Tanner AN, Williams NN, Keane FB. The pros and cons of laparoscopic cholecystectomy
and extracorporeal shock wave lithotripsy in the management of gallstone disease. Ann R Coll Surg Engl 1994;76:42-6.
173. Dashow L, Friedman I, Kempner R, Rudick J, McSherry C. Initial experience with laparoscopic cholecystectomy at the Beth
Israel Medical Center. Surg Gynecol Obstet 1992; 175:25-30.
174. Dauleh MI, Rahman S, Townell NH. Open versus laparoscopic cholecystectomy: a comparison of postoperative temperature.
J R Coll Surg Edinb 1995; 40:116-8.
175. Davies MG, O’Broin E, Mannion C, et al. Audit of open cholecystectomy in a district general hospital. Br J Surg 1992; 79:
314-6.
176. Davis CJ, Arregui ME, Nagan RF, Shaar C. Laparoscopic cholecystectomy: the St. Vincent experience. Surg Laparosc Endosc
1992; 2:64-8.
177. DeIorio AV, Jr., Vitale GC, Reynolds M, Larson GM. Acute biliary pancreatitis. The roles of laparoscopic cholecystectomy and
endoscopic retrograde cholangiopancreatography. Surg Endosc 1995; 9:392-6.
178. del Santo P, Kazarian KK, Rogers JF, Bevins PA, Hall JR. Prediction of operative cholangiography in patients undergoing
elective cholecystectomy with routine liver function chemistries. Surgery 1985;98:7-11.
179. Delaitre B, Testas P, Dubois F, et al. [Complications of cholecystectomy by laparoscopic approach. Apropos of 6512 cases].
Chirurgie 1992; 118:92-9.
180. Denning DA, Lipshy KA. Missed pathology following laparoscopic cholecystectomy: a cause for concern? Am Surg 1995;
61:117-20.
181. Deveney KE. The early experience with laparoscopic cholecystectomy in Oregon. Arch Surg 1993; 128:627-32.
182. Dexter SP, Martin IG, Marton J, McMahon MJ. Long operation and the risk of complications from laparoscopic
cholecystectomy. Br J Surg 1997; 84:464-6.
183. Deziel DJ, Millikan KW, Economou SG, Doolas A, Ko ST, Airan MC. Complications of laparoscopic cholecystectomy: a national
survey of 4,292 hospitals and an analysis of 77,604 cases. Am J Surg 1993; 165:9-14.
184. Diehl AK. Epidemiology and natural history of gallstone disease. Gastroenterol Clin North Am 1991; 20:1-19.
185. Diehl AK, Sugarek NJ, Todd KH. Clinical evaluation for gallstone disease: usefulness of symptoms and signs in diagnosis. Am J
Med 1990; 89:29-33.
186. Diehl AK. Trends in cholecystectomy rates in the United States. Lancet 1987;II:683.
171
187. Diettrich NA, Cacioppo JC, Davis RP. The vanishing elective cholecystectomy. Trends and their consequences. Arch Surg
1988;123:810-4.
188. Dilawari JB, Chawla YK, Singhal AK, Kataria S. Postcholecystectomy syndrome in northern India – study on the diagnostic
and therapeutic role of ERCP. Gastroenterol Jpn 1990; 25:394-9.
189. Dion YM, Morin J. Laparoscopic cholecystectomy: a review of 258 patients. Can J Surg 1992; 35:317-20.
190. Dionigi R, Dominioni L, Benevento A, et al. Effects of surgical trauma of laparoscopic vs. open cholecystectomy. Hepatogastroenterology 1994; 41:471-6.
191. Dobronte Z. [Late results of endoscopic sphincterotomy in patients with intact gallbladder]. Z Gastroenterol 1993; 31
Suppl 2.
192. Dobson AJ, Kuulasmaa K, Eberle E, Scherer J. Confidence interval for weighted sums of poisson parameters. Stat Med
1991;10:457-62.
193. Donald JJ, Cheslyn Curtis S, Gillams AR, Russell RC, Lees WR. Percutaneous cholecystolithotomy: is gall stone recurrence
inevitable? Gut 1994; 35:692-5.
194. Downs SH, Black NA, Devlin HB, Royston CMS, Russell RCG. A systematic review of the effectiveness and safety of
laparoscopic cholecystectomy. Ann R Coll Surg Eng 1996;78 no 3 (part II):241-323.
195. Dorazio RA. Selective operative cholangiography in laparoscopic cholecystectomy. Am Surg 1995; 61:911-3.
196. Dubois B, Nagy AG, Anderson D, Simpson WT, Appleby JP. Comparison of initial laparoscopic cholecystectomy at a
community hospital versus a teaching hospital. Can J Surg 1995; 38:439-44.
197. Dubois F, Berthelot B. Cholécystectomie par mini-laparotomie. Nouv Presse Med 1982;11:1139-41.
198. Dubois F, Berthelot G, Levard H. [Cholecystectomy by coelioscopy (see comments]). Presse Med 1989;18:980-2.
199. Dubois F, Berthelot G, Levard H. Cholécystectomie sous caelioscopie. 330 cas. Chirurgie 1990;116:248-50.
200. Dubois F, Berthelot G, Levard H. Laparoscopic cholecystectomy: Historic perspective and personal experience. Surg Laparosc
Endosc 1991;1:52-7.
201. Dubois F, Berthelot G, Levard H. Cholécystectomie sous caelioscopie. Technique et complications. A propos de 2665 cas. Bull
Acad Natle Méd 1995;179:1059-68.
202. Dunham R, Sackier JM. Is there a dilemma in adequately training surgeons in both open and laparoscopic biliary surgery?
Surg Clin North Am 1994; 74:913-21.
203. Dunn D, Nair R, Fowler S, McCloy R. Laparoscopic cholecystectomy in England and Wales: results of an audit by the Royal
College of Surgeons of England see comments. Ann R Coll Surg Engl 1994; 76:269-75.
204. Dunn FH, Christensen EC, Reynolds J, Jones V, Fordtran JS. Cholecystokinin cholecystography. JAMA 1974;228:997-1003.
205. duPlessis DJ, Jersky J. The management of acute cholecystitis. Surg Clin North Am 1973;53:1071.
206. Eggleston JM, London SD, Glasheen WP, et al. A retrospective analysis of 6,387 cholecystectomies. Med Prog Technol 1995;
21:85-90.
207. Eidsvoll BE, Aadland E, Stiris M, Lunde OC. Dissolution of cholesterol gallbladder stones with methyl tert-butyl ether in
patients with increased surgical risk. Scand J Gastroenterol 1993; 28:744-8.
208. Eidsvoll BE, Aadland E, Stiris M, Lunde OC. [Dissolution of gallstones with methyl-tert-butyl ether. An alternative to surgery
in high risk patients]. Tidsskr Nor Laegeforen 1994; 114:567-9.
209. Einarsson K, Angelin B, Kelter U, Nyberg B, Sonnenfeld T. Biliary colic without evidience of gallstones: Diagnosis, biliary lipid
metabolism and treatment. Acta Chir Scand 1986;530(suppl):31-4.
210. Eldar S, Sabo E, Nash E, Abrahamson J, Matter I. Laparoscopic cholecystectomy for acute cholecystitis: prospective trial.
World J Surg 1997; 21:540-5.
211. Elfström J. The timing of cholecystektomy in patients with gallstone pancreatitis. A retrospective analysis of 89 patients. Acta
Chir Scand 1978;144:487-90.
172
212. Elfving G, Lehtonen T, Her H. Clinical significance of primary hyperplasia of gallbladder mucosa. Ann Surg 1967;165:61-68
213. Escarce JJ, Chen W, Schwartz JS. Falling cholecystectomy thresholds since the introduction of laparoscopic cholecystectomy
[see comments]. JAMA 1995; 273:1581-5.
214. Ewing HP, Cade RJ, Cocks JR, Collopy BT, Thompson GA. Developing clinical indicators for cholecystectomy. Aust N Z J Surg
1993; 63:181-5.
215. Fabre JM, Fagot H, Domergue J, et al. [Celioscopic cholecystectomy in simple and complicated cholelithiasis. Apropos of 392
cases]. Ann Chir 1992; 46:330-4.
216. Fan ST, Lai EC, Mok FP, Lo CM, Zheng SS, Wong J. Early treatment of acute biliary pancreatitis by endoscopic papillotomy,
see comments. N Engl J Med 1993; 328:228-32.
217. Farrell T, Mahon T, Daly L, Masterson J. Identification of inappropriate radiological referrals with suspected gallstones:
a prospective audit. Br J Radiol 1994; 67:32-5.
218. Farsakh NAA, Roweily E, Steitieh M, Butchoun R, Khalil B. Prevalence of Helicobacter pylori in patients with gall stones
before and after cholecystectomy: a longitudinal study. Gut 1995; 36:675-8.
219. Farsakh NAA, Stietieh M, Farsakh FAA. The postcholecystectomy syndrome. A role for duodenogastric reflux. J Clin
Gastroenterol 1996;22:197-201.
220. delFavero G, Caroli A, Meggiato T, Volpi A, Scalon P, Puglisi A, di Mario F. Natural history of gallstones in non-insulindependent diabetes mellitus. A prospective 5-year follow-up. Dig Dis Sci 1994;39:1704-7.
221. Fendrick AM, de Pouvourville G, Bitker C, Pelletier G. Treatment of symptomatic cholelithiasis in France. A decision analysis
comparing cholecystectomy and biliary lithotripsy. Int J Technol Assess Health Care 1992; 8:166-84.
222. Fendrick AM, Gleeson SP, Cabana MD, Schwartz JS. Asymptomatic gallstones revisited. Is there a role for laparoscopic
cholecystectomy? Arch Fam Med 1993; 2:959-68.
223. Fenster LF, Lonborg R, Thirlby RC, Traverso LW. What symptoms does cholecystectomy cure? Insights from an outcomes
measurement project and review of the literature. Am J Surg 1995; 169:533-8.
224. Ferraris VA. The empty gallbladder syndrome – results of operation for noncalculous biliary disorders. West J Med
1986;144:437-40.
225. Ferzli G, Massaad A, Piperno B, Fiorillo M, Kiel T. Changing experiences with 1848 cholecystectomies at a single institution.
J Laparoendosc Surg 1996; 6:1-11.
226. Feussner H, Ungeheuer A, Lehr L, Siewert JR. [Laparoscopic cholecystectomy – personal results of the first 500 operations.]
Bildgebung 1992; 59 Suppl 1:54-6.
227. Fiallo VM, O’Connor FX, Reed WP. Preceptored introduction of laparoscopic techniques for cholecystectomy into a large
university-affiliated medical center. Surg Endosc 1994; 8:1063-6.
228. Fielding GA. Laparoscopic cholecystectomy. Aust N Z J Surg 1992; 62:181-7.
229. Finkelstein R, Yassin K, Suissa A, Lavy A, Eidelman S. Failure of cefonicid prophylaxis for infectious complications related to
endoscopic retrograde cholangiopancreatography [see comments]. Clin Infect Dis 1996; 23:378-9.
230. Fiorillo MA, Davidson PG, Fiorillo M, D’Anna JA, Jr., Sithian N, Silich RJ. 149 ambulatory laparoscopic cholecystectomies. Surg
Endosc 1996; 10:52-6.
231. Fitzgibbons RJ, Jr., Schmid S, Santoscoy R, et al. Open laparoscopy for laparoscopic cholecystectomy. Surg Laparosc Endosc
1991; 1:216-22.
232. Fletcher DR. Changes in the practice of biliary surgery and ERCP during the introduction of laparoscopic cholecystectomy to
Australia: their possible significance. Aust N Z J Surg 1994; 64:75-80.
233. Flowers JL, Bailey RW, Scovill WA, Zucker KA. The Baltimore experience with laparoscopic management of acute
cholecystitis. Am J Surg 1991; 161:388-92.
234. Foerster EC, Matek W, Domschke W. Endoscopic retrograde cannulation of the gallbladder: direct dissolution of gallstones.
Gastrointest Endosc 1990; 36:444-50.
173
235. Folsch UR, Nitsche R, Ludtke R, Hilgers RA, Creutzfeldt W. Early ERCP and papillotomy compared with conservative
treatment for acute biliary pancreatitis. The German Study Group on Acute Biliary Pancreatitis [see comments]. N Engl J Med
1997; 336:237-42.
236. Forse A, El Beheiry H, Butler PO, Pace RF. Indomethacin and ketorolac given preoperatively are equally effective in reducing
early postoperative pain after laparoscopic cholecystectomy. Can J Surg 1996; 39:26-30.
237. Forster R, Lindlar R, Vorbeck B, Rothmund M. Is simultaneous cholecystectomy and choledochal exploration obsolete?. Dtsch
Med Wochenschr 1990; 115:563-9.
238. Foutch PG. A prospective assessment of results for needle-knife papillotomy and standard endoscopic sphincterotomy.
Gastrointest Endosc 1995; 41:25-32.
239. Fowkes FGR. Cholecystectomy and surgical ressources in Scotland. Health Bull 1980;38:126-32.
240. Frank ED, McKay W, Rocco A, Gallo JP. Interpleural bupivacaine for postoperative analgesia following cholecystectomy:
a randomized prospective study. Reg Anesth 1990; 15:26-30.
241. Frankel AM, Horowitz GD. Nasoduodenal tubes in short-stay cholecystectomy. Surg Gynecol Obstet 1989; 168:433-6.
242. Fraser GM, Pilpel D, Kosecoff J, Brook RH. Effect of panel composition on appropriateness ratings. Int J Qual Health Care 1994;
6:251-5.
243. Fraser GM, Pilpel D, Hollis S, Kosecoff J, Brook RH. Indications for cholecystectomy: the results of a consensus panel approach.
Qual Assur Health Care 1993; 5:75-80.
244. Fraser GM, Pilpel D, Hollis S, Kosecoff J, Brook RH. The agreed indications and contra-indications for cholecystectomy.
Qual Assur Health Care 1993; 5:81-5.
245. Frazee RC, Roberts JW, Symmonds R, et al. What are the contraindications for laparoscopic cholecystectomy? Am J Surg
1992; 164:491-4.
246. Frazee RC, Roberts JW, Okeson GC, et al. Open versus laparoscopic cholecystectomy. A comparison of postoperative
pulmonary function. Ann Surg 1991; 213:651-3.
247.
Freeman JB, Cohen WN. Cholecystokinin cholangiography and analysis of duodenal bile in the investigation of pain in the
right upper quadrant of the abdomen without gallstones. Surg Gyn Obst 1975;140:371-6.
248. Freeman ML, Nelson DB, Sherman S, et al. Complications of endoscopic biliary sphincterotomy [see comments]. N Engl J
Med 1996; 335:909-18.
249. French EB, Robb WAT. Biliary and renal colic. BMJ 1963;2:135-8.
250. Frenette L, Boudreault D, Guay J. Interpleural analgesia improves pulmonary function after cholecystectomy. Can J Anaesth
1991; 38:71-4.
251. Friedman GD, Raviola CA, Fireman B. Prognosis of gallstones with mild or no symptoms: 25 years of follow-up in a health
maintenance organization. J Clin Epidemiol 1989; 42:127-36.
252.
Friedman LS, Roberts MS, Brett AS, Marton KI. Management of asymptomatic gallstones in the diabetes patient.
A decision analysis. Ann Int Med 1988;109:913-9.
253. Friedman RL, Pace BW, Tallon RW. Resident education in laparoscopic cholecystectomy Laparoscopic cholecystectomy:
a technologic assessment. Surg Endosc 1996; 27:52-4.
254. Fromm H, Malavolti M. Bile acid dissolution therapy of gallbladder stones. Baillieres Clin Gastroenterol 1992; 6:689-95.
255. Frykberg ER, Duong TC, LaRosa JJ, Etienne HB. Chronic acalculous gallbladder disease: A clinical variant. South Med J
1988;81:13537.
256. Fujii Y, Tanaka H, Toyooka H. Granisetron reduces the incidence and severity of nausea and vomiting after laparoscopic
cholecystectomy. Can J Anaesth 1997; 44:396-400.
257. Fullarton GM, Bell G. Prospective audit of the introduction of laparoscopic cholecystectomy in the west of Scotland. West of
Scotland Laparoscopic Cholecystectomy Audit Group. Gut 1994; 35:1121-6.
174
258. Fullarton GM, Darling K, Williams J, MacMillan R, Bell G. Evaluation of the cost of laparoscopic and open cholecystectomy
[see comments]. Br J Surg 1994; 81:124-6.
259. Fullarton GM, Murray WR. Evaluation of endoscopic sphincterotomy in sphincter of Oddi dysfunction. Endoscopy 1992;
24:199-202.
260. Funch Jensen P, Ebbehoj N. Sphincter of Oddi motility. Scand J Gastroenterol Suppl 1996; 216:
261. Gaetini A, Camandona M, De Simone M, Giaccone M. Cholecystectomy by minilaparotomy. Minerva Chir 1997; 52:13-6.
262. Gai H, Thiele H. Ultrasound selection criteria for laparoscopic cholecystectomy. Chirurg 1992; 63:426-31.
263. Galatola G, Jazrawi RP, Kupfer RM, Maudgal DP, Lanzini A, Joseph AEA, Northfield TC. Value of different symptom complexes
for clinical diagnosis of gallstones in outpatients presenting with abdominal pain. Eur J Gastroenterol Hepatol 1991;3:
623-5.
264.
Ganey JB, Johnson PA, Prillaman PE, McSwain GR. Cholecystectomy: Clinical experience with a large series. Am J Surg
1986;151:352-6.
265. Garber SM, Korman J, Cosgrove JM, Cohen JR. Early laparoscopic cholecystectomy for acute cholecystitis. Surg Endosc 1997;
11:347-50.
266. Garcia Caballero M, Vara Thorbeck C. The evolution of postoperative ileus after laparoscopic cholecystectomy. A comparative
study with conventional cholecystectomy and sympathetic blockade treatment. Surg Endosc 1993; 7:416-9.
267. Garcia-Valdecasas JC, Almenara R, Cabrer C, deLacy AM, Sust M, Taurá P, Fuster J, Grande L, Pera M, Sentis J, Visa J.
Subcostal incision versus midline laparotomy in gallstone surgery: A prospective and randomized trial. Br J Surg
1988;75:473-5.
268. Gebhardt C, Meinl P. Lesions of the bile ducts in open cholecystectomy. Chirurg 1994; 65:741-7.
269. Geenen JE, Hogan WJ, Dodds WJ, Toouli J, Venu RP. The efficacy of endoscopic sphincterotomy after cholecystectomy in
patients with sphincter-of-oddi dysfunction. N Eng J Med 1989;320:82-7.
270. Gibney RG, Chow K, So CB, Rowley VA, Cooperberg PL, Burhenne HJ. Gallstone recurrence after cholecystolithotomy. AJR Am
J Roentgenol 1989; 153:287-9.
271. Gilks WR, Richardson S, Spigelhalter DJ. Markov Chain Monte Carlo in practice 1996:359-79, Chapman&Hall.
272. Gillams A, Curtis SC, Donald J, Russell C, Lees W. Technical considerations in 113 percutaneous cholecystolithotomies.
Radiology 1992; 183:163-6.
273.
Gilliland TM, Traverso LW. Modern standards for comparison of cholecystectomy with alternative treatments for
symptomatic cholelithiasis with emphasis on long-term relief of symptoms. Surg Gynecol Obstet 1990; 170:39-44.
274. Gilliland TM, Traverso LW. Cholecystectomy provides long-term symptom relief in patients with acalculous gallbladders [see
comments]. Am J Surg 1990; 159:489-92.
275. Glambek I, Arnesjo B, Soreide O. Correlation between gallstones and abdominal symptoms in a random population. Results
from a screening study. Scand J Gastroenterol 1989; 24:277-81.
276. Glambek I, Kvaale G, Arnesjö B, Søreide O. Prevalence of gall stones in a Norwegian population. Scand J Gastroenterol
1987;22:1089-94.
277. Glenn F, Frey C. Re-evaluation of the treatment of pancreatitis associated with biliary tract disease. Ann Surg 1964;160:
723-36.
278. Glenn F, Mannix H. The acalculous gallbladder. Ann Surg 1956;144:670-8.
279. Glenn F, McSherry K. Etiological factors in fatal complications following operations upon the biliary tract. Ann Surg
1963;157:695-706.
280. Go PM, Schol F, Gouma DJ. Laparoscopic cholecystectomy in The Netherlands. Br J Surg 1993; 80:1180-3.
281. Go PM, Stolk MF, Obertop H, et al. Symptomatic gallbladder stones. Cost-effectiveness of treatment with extracorporeal
shock-wave lithotripsy, conventional and laparoscopic cholecystectomy. Surg Endosc 1995; 9:37-41.
175
282. Goco IR, Chambers LG. “Mini-cholecystectomy” and operative cholangiography. A means of Cost Containment. Am Surg
1983;49:143-5.
283.
Goldman G, Kahn PJ, Alon R, Wiznitzer T. Biliary colic treatment and acute cholecystitis prevention by prostaglandin
inhibitor [see comments]. Dig Dis Sci 1989; 34:809-11.
284. Goldstein F, Grunt R, Margulies M. Cholecystokinin cholecystography in the differentiel diagnosis of acalculous gallbladder
disease. Am J Dig Dis 1974;19:835-49.
285. Gomand L, Vandenbroucke J, DeGroote J. De natuurlijke evolutie van colelithiase. Tijdschr Gastrenterol 1966;9:594-608.
286. Gough MH. “The cholecystogram is normal” ... but ... BMJ 1977;1:960-2
287. Gouma DJ, Go PM. Bile duct injury during laparoscopic and conventional cholecystectomy. J Am Coll Surg 1994; 178:
229-33.
288. Graber JN, Schultz LS, Pietrafitta JJ, Hickok DF. Complications of laparoscopic cholecystectomy. Las Surg Med 1992;12:92-7.
289. Gracie WA, Ransohoff DF. The natural history of silent gallstones. The innocent gallstone is not a myth. N Engl J Med
1982;307:798-800.
290. Graves HA, Jr., Ballinger JF, Anderson WJ. Appraisal of laparoscopic cholecystectomy. Ann Surg 1991; 213:655-62.
291. Greenhalgh T. Papers that summarise other papers (systematic reviews and meta-analyses). BMJ 1997;315:672-5.
292. Gregg RO. The case for selective cholangiography. Am J Surg 1988;155:540-5.
293. Grogono JL, Woods WGA. Selective use of operative cholangiography. World J Surg 1986;10:1009-13.
294. Guelrud M, Mendoza S, Rossiter G, Ramirez L, Barkin J. Effect of nifedipine on sphincter of Oddi motor activity: Studies in
healthy volunteers and patients with biliary dyskinesia. Gastroenterology 1988;95:1050-8.
295.
Gunn A, Keddie N. Some clinical observations on patients with gallstones. Lancet 1972;ii:239-41.
296. Gunn A, Keddie NC, Box H. Acalculous gall-bladder disease. Br J Surg 1973;60:213-5.
297. Hafif A, Gutman M, Kaplan O, Winkler E, Rozin RR, Skornick Y. The management of acute cholecystitis in elderly patients.
Am Surg 1991; 57:648-52.
298. Hakanson E, Bengtsson M, Rutberg H, Ulrick AM. Epidural morphine by the thoracic or lumbar routes in cholecystectomy.
Effect on postoperative pain and respiratory variables. Anaesth Intensive Care 1989; 17:166-9.
299. Hall RC. Short Hospital stay: Two hospital days for cholecystectomy. Am J Surg 1987;154:510-5.
300. Halverson JD, Garner BA, Siegel BA, et al. The use of hepatobiliary scintigraphy in patients with acalculous biliary colic. Arch
Intern Med 1992; 152:1305-7.
301. Hamilton S, Leahy AL, Darzi A, Keane FB. Biliary intervention via minicholecystostomy published erratum appears in Clin
Radiol 1991 Apr;43(4):289. Clin Radiol 1990; 42:418-22.
302. Hammarström L-E, Holmin T, Stridbeck H. Endoscopic treatment of bile duct calculi in patients with gallbladder in situ:
Long-term outcome and factors predictive of recurrent symptoms. Scan J Gastroenterol 1996;31:294-301.
303. Hammarström L-E, Holmin T, Stridbeck H, Ihse I. Long-term follow-up of a prospective randomized study of endoscopic
versus surgical treatment of bile duct calculi in patients with gallbladder in situ. Br J Surg 1995;82:1516-21.
304. Hanis CL, Hewett Emmett D, Kubrusly LF, et al. An ultrasound survey of gallbladder disease among Mexican Americans in
Starr County, Texas: frequencies and risk factors. Ethn Dis 1993; 3:32-43.
305. Hansell DT, Millar MA, Murray WR, Gray GR, Gillespie G. Endoscopic sphincterotomy for bile duct stones in patients with
intact gallbladders [see comments]. Br J Surg 1989; 76:856-8.
306. Hansen S. Undersøgelser over cholelithiasis. Ugeskr Læg 1922;84:405-21.
307. Hardy KJ, Miller H, McNeil J, Shulkes A. Measurement of surgical costs: a clinical analysis. Aust N Z J Surg 1994; 64:607-11.
308. Hardy KJ, Miller H, Fletcher DR, Jones RM, Shulkes A, McNeil JJ. An evaluation of laparoscopic versus open cholecystectomy.
Med J Aust 1994; 160:58-62.
176
309. Hauer Jensen M, Karesen R, Nygaard K, et al. Prospective randomized study of routine intraoperative cholangiography
during open cholecystectomy: long-term follow-up and multivariate analysis of predictors of choledocholithiasis. Surgery
1993; 113:318-23.
310. Hauer-Jensen M, Kåresen R, Nygaard K, Solheim K, Amlie E, Havig Ø, Viddal KO. Predictive ability of choledocholithiasis
indicators. A prospective evaluation. An Surg 1985;202:64-8.
311. Hauer-Jensen M, Kåresen R, Nygaard K, Solheim K, Amlie E, Havig Ø, Viddal KO. Consequences of routine peroperative
cholangiography during cholecystectomy for gallstone disease: A prospective, randomized study. World J Surg 1986;10:9961002.
312. Harvey MH, Ross AHMcL, Sauven PD. Introduction of laparoscopic cholecystectomy in a large teaching hospital:
Independent audit of the first three year. Br J Surg 1996;83:132-8.
313. Hawasli A. To drain or not to drain in laparoscopic cholecystectomy: rationale and technique. Surg Laparosc Endosc 1992;
2:128-30.
314. Hazel SJ van der, Speelman P, Dankert J, Huibregtse K, Tytgat GNJ, Leeuwen DJ van. Piperacillin to prevent cholangitis after
endoscopic retrograde cholangiopancreatography. A randomized, controlled trial. Ann Intern Med 1996;125:442-7.
315. Heaton KW, Braddon FEM, Mountford RA, Hughes AO, Emmett PM. Symptomatic and silent gall stones in the community.
Gut 1991;32:316-20.
316. Heberer G, Paumgartner G, Sauerbruch T, Sackmann M, Rrämling H-J, Delius M, Brendel W. A retrospective analysis of 3
year’s experience of an interdisciplinary approach to gallstone disease including shock-waves. Ann Surg 1988;208:274-8.
317. Hederström E, Forsberg L, Herlin P, Holmin T. Fatty meal provocation monitored by ultrasonography. Acta Radiologica
1988;29:207-10.
318. Hellstern A, Leuschner M, Frenk H, Dillinger HW, Caspary W, Leuschner U. Gall stone dissolution with methyl tert-butyl
ether: how to avoid complications. Gut 1990; 31:922-5.
319. Hellstern A, Leuschner U, Gatzen M. Percutaneous transhepatic litholysis--indications, results, risks. Langenbecks Arch Chir
Suppl II Verh Dtsch Ges Chir 1990; 1217-8.
320. Hellstern A, Rubesam D, Leuschner M, Wendt T, Fuchs H, Leuschner U. Percutaneous transhepatic gallstone dissolution with
methyl tert-butyl ether in complicated stone diagnosis and gallbladder anomalies. Endoscopy 1990; 22:254-8.
321. Hermanek P, Hohenberger W. The importance of volume in colorectal cancer surgery. Eur J Surg Onc 1996;22:213-5.
322. Hermann RE. Surgery for acute and chronic cholecystitis. Surgical Clinics of North America 1990;70:1263-75.
323. Hershman MJ, Rosin RD. Laparoscopic laser cholecystectomy: our first 200 patients. Ann R Coll Surg Engl 1992; 74:242-7.
324. Herzog U, Kocher T, Looser C, Schuppisser JP, Ackermann C, Tondelli P. Laparoscopic cholecystectomy. Initial experiences
and results in 278 patients. Dtsch Med Wochenschr 1992; 117:775-81.
325. Herzog U, Messmer P, Sutter M, Tondelli P. Surgical treatment for cholelithiasis. Surg Gynecol Obstet 1992; 175:238-42.
326. Hill J, Martin DF, Tweedle DE. Risks of leaving the gallbladder in situ after endoscopic sphincterotomy for bile duct stones.
Br J Surg 1991; 78:554-7.
327. Hilsberg P. Det betaler sig at bruge flergangsudstyr. Sygeplejersken 1997;97:32-7
328. Hinkel CL, Moller GA. Correlation of symptoms, age, sex, and habitus with cholecystografic findings in 1000 consecutive
examinations. Gastroenterology 1957;32:807-15
329. Hjelmqvist B, Gustavson K. Svenska laparoskopiregistret. Hygiea 1995;104:215.
330. Hofmann AF, Amelsberg A, Esch O, et al. Successful topical dissolution of cholesterol gallbladder stones using ethyl
propionate. Dig Dis Sci 1997; 42:1274-82.
331. Hofmann AF. Primary and secondary prevention of gallstone disease: implications for patient management and research
priorities. Am J Surg 1993; 165:541-8.
332. Hogan WJ, Greenen JE. Biliary dyskinesia. Endoscopy 1988;20:179-83.
177
333. Holbling N, Pilz E, Feil W, Schiessel R. Laparoscopic cholecystectomy – a meta-analysis of 23,700 cases and status of a
personal patient sample Laparoskopische Cholezystektomie – eine Metaanalyse von 23,700 Fallen und der Stellenwert im
eigenen Patientenkollektiv. Wien Klin Wochenschr 1995; 107:158-62.
334. Holmes SA, Whitfield HN. The current status of lithotripsy. Br J Urol 1991; 68:337-44.
335. Huang CS, Tai FC, Shi MY, Chen DF, Wang NY. Complications of laparoscopic cholecystectomy: an analysis of 200 cases. J
Formos Med Assoc 1992; 91:785-92.
336. Huang FY, Fan SZ, Wang MS, Chen TL, Sun WZ, Lin SY. Comparison of continuous epidural infusion of fentanyl and
fentanyl-bupivacaine for post cholecystectomy pain control. Ma Tsui Hsueh Tsa Chi 1990; 28:9-13.
337. Huang SM, Wu CW, Lui WY, P’eng FK. A prospective randomised study of laparoscopic v. open cholecystectomy in aged
patients with cholecystolithiasis. S Afr J Surg 1996; 34:177-9.
338. Hubens A, Van de Kelft E, Roland J. The influence of cholecystectomy on the duodenogastric reflux of bile.
Hepatogastroenterology 1989; 36:384-6.
339. Hultman CS, Herbst CA, McCall JM, Mauro MA. The efficacy of percutaneous cholecystostomy in critically ill patients.
Am Surg 1996; 62:263-9.
340. Hunter JG. Laparoscopic transcystic common bile duct exploration. Am J Surg 1992;163:53-8.
341. Hwang M-H, Mo L-R, Chen G-D, Yang J-C, Lin C, Yueh S-K. Percutaneous transhepatic cholecystic ultrasonic lithotripsy.
Gastrointest Endoscopy 1987;33:301-3.
342. Hwang MH, Tsai CC, Mo LR, et al. Percutaneous choledochoscopic biliary tract stone removal: experience in 645 consecutive
patients. Eur J Radiol 1993; 17:184-90.
343. Ihasz M, Hung CM, Regoly Merei J, et al. Complications of laparoscopic cholecystectomy in Hungary: a multicentre study of
13,833 patients. Eur J Surg 1997; 163:267-74.
344. Ingoldby CJ, el Saadi J, Hall RI, Denyer ME. Late results of endoscopic sphincterotomy for bile duct stones in elderly patients
with gall bladders in situ. Gut 1989; 30:1129-31.
345. Inui K, Nakazawa S, Yoshino J, et al. Percutaneous cholecystoscopy. Endoscopy 1989; 21 Suppl 1:
346.
Iversen A. VII Cholecystectomia. Gynaekologiske og obstetriciske meddelelser 1889;7:106-40.
347. Jacobs M, Verdeja JC, Goldstein HS. Laparoscopic cholecystectomy in acute cholecystitis. J Laparoendosc Surg 1991; 1:
175-7.
348. Jakobs R, Adamek HE, Maier M, et al. Fluoroscopically guided laser lithotripsy versus extracorporeal shock wave lithotripsy for
retained bile duct stones: a prospective randomised study. Gut 1997; 40:678-82.
349. Jan YY, Chen HM, Wang CS, Chen MF. Biliary complications during and after laparoscopic cholecystectomy.
Hepatogastroenterology 1997; 44:370-5.
350. Jan YY, Chen MF. Laparoscopic versus open cholecystectomy: a prospective randomized study. J Formos Med Assoc 1993;
92 Suppl 4:243-9
351. Janowitz P, Schumacher KA, Swobodnik W, Kratzer W, Tudyka J, Wechsler JG. Transhepatic topical dissolution of gallbladder
stones with MTBE and EDTA. Results, side effects, and correlation with CT imaging. Dig Dis Sci 1993; 38:2121-9.
352. Janzon L, Aspelin P, Eriksson S, Hildell J, Trell E, Östberg H. Ultrasonographic screening for gallstone disease in middle-aged
women. Detection rate, symptoms, and biochemical features. Scand J Gastroenterol 1985;20:706-10.
353. Jazrawi S, Walsh TN, Byrne PJ, et al. Cholecystectomy and oesophageal reflux: a prospective evaluation. Br J Surg 1993;
80:50-3.
354. Jensen KH, Jørgensen T. Incidence of gallstones in a Danish population. Gastroenterology 1991;100:790-4.
355. Johansson B, Glise H, Hallerback B, Dalman P, Kristoffersson A. Preoperative local infiltration with ropivacaine for
postoperative pain relief after cholecystectomy [see comments]. Anesth Analg 1994; 78:210-4.
356. Johnson AG. Cholecystectomy and gallstone dyspepsia. Ann R Coll Surg Engl 1975;56:69-80.
178
357. Jones DB, Dunnegan DL, Soper NJ. The influence of intraoperative gallbladder perforation on long-term outcome after
laparoscopic cholecystectomy. Surg Endosc 1995;9:977-80.
358.
Jones DB, Soper NJ, Brewer JD, et al. Chronic acalculous cholecystitis: laparoscopic treatment. Surg Laparosc Endosc 1996;
6:114-22.
359. Jonson G, Nilsson DM, Nilsson T. Cystic duct remnants and biliary symptoms after cholecystectomy. A randomised
comparison of two operative techniques. Eur J Surg 1991; 157:583-6.
360. Jorgensen JO, Gillies RB, Hunt DR, Caplehorn JR, Lumley T. A simple and effective way to reduce postoperative pain after
laparoscopic cholecystectomy. Aust N Z J Surg 1995; 65:466-9.
361.
Joris J, Thiry E, Paris P, Weerts J, Lamy M. Pain after laparoscopic cholecystectomy: characteristics and effect of
intraperitoneal bupivacaine. Anesth Analg 1995; 81:379-84.
362.
Juvonen T. Pathogenesis of gallstones. Scand J Gastroenterol 1994;29:577-82.
363.
Järhult J. The importance of volume for outcome in cancer surgery – an overview. Eur J Surg Onc 1996;22:205-10
364.
Järvinen HJ, Hästbacka J. Early cholecystectomy for acute cholecystitis. A prospective randomized study. Ann Surg
1980;191:501-5.
365.
Jørgensen T. Prevalence of gallstones in a Danish population. Am J Epidemiol 1987;126:912-21.
366.
Jørgensen T. Gall stones in a Danish population: Fertility period, pregnancies, and exogenous female sex hormones. Gut
1988;29:433-9.
367. Jørgensen T. Gallstones in a Danish population: Familial occurrence and social factors. J Biosoc Sci 1988;20:111-20.
368. Jørgensen T. Abdominal symptoms and gallstone disease: an epidemiological investigation. Hepatology 1989; 9:856-60.
369. Jørgensen T. Gall stones in a Danish population. Relation to weight, physical activity, smoking, coffee consumption, and
diabetes mellitus. Gut 1989; 30:528-34.
370. Jørgensen T. Gallstones. An epidemiological investigation. Dan Med Bull 1990; 37:336-46.
371.
Jørgensen T. Center for Sygdomsforebyggelse. 1997.
372. Jørgensen T, Borch-Johnsen K. Gallstones and glucose metabolism. An epidemiological investigation. Gut
1995;37(suppl2):A194.
373. Jørgensen T, Jensen KH. Hvem har galdesten? Nyere epidemiologiske undersøgelser. Ugeskr Læg 1991;153:2612-7.
374. Jørgensen T, Jørgensen LM. Gallstones and diet in a Danish population. Scand J Gastroenterol 1989; 24:821-6.
375. Jørgensen T, Kay L, Schultz Larsen K. The epidemiology of gallstones in a 70-year-old Danish population. Scand J
Gastroenterol 1990; 25:335-40.
376. Jørgensen T, Stubbe-Teglbjærg J, Wille-Jørgensen PA, Bille T, Thorvaldsen P. Persistent pain after cholecystectomy.
A prospective investigation. Scand J Gastroenterol 1991;26:124-8.
377. Kahn KL, Park RE, Brook RH, Chassin MR, Kosecoff J, Fink A, Keesey JW, Solomon DH. The effect of comorbidity on
appropriateness ratings for two gastrointestinal procedures. J Clin Epidemiol 1988;41:115-122.
378. Kane RL, Lurie N, Borbas C, et al. The outcomes of elective laparoscopic and open cholecystectomies [see comments]. J Am
Coll Surg 1995; 180:136-45.
379. Karayiannakis AJ, Makri GG, Mantzioka A, Karousos D, Karatzas G. Postoperative pulmonary function after laparoscopic and
open cholecystectomy. Br J Anaesth 1996; 77:448-52.
380. Kastrissios H, Mogg GA, Triggs EJ, Higbie JW. Interpleural bupivacaine infusion compared with intravenous pethidine
infusion after cholecystectomy. Anaesth Intensive Care 1991; 19:539-45.
381. Kaufman M, Weissberg D, Schwartz I, Moses Y. Cholecystostomy as a definitive operation. Surg Gynecol Obstet 1990;
170:533-7.
179
382. Kay L, Jørgensen T, Jensen KH. Epidemiology of abdominal symptoms in a random population: Prevalence, incidence, and
natural history. Eur J Epidemiol 1994;10:559-66.
383. Kawai K, Akasaka Y, Murakami M. Endoscopic sphincterotomy of the ampulla of vater. Gastrointestinal Endosc 1974;20:
148-51.
384. Keddie NC, Gough AL, Galland RB. Acalculous gallbladder disease: a prospective study. Br J Surg 1976;63:797-8.
385. Kellett MJ, Russell RC, Wickham JE. Percutaneous cholecystolithotomy. Endoscopy 1989; 21 Suppl 1:
386. Kellett MJ, Wickham JEA, Russell RCG. Percutaneous cholecystolithotomy. Br med J 1988;296:453-5.
387. Kelley JE, Burrus RG, Burns RP, Graham LD, Chandler KE. Safety, efficacy, cost, and morbidity of laparoscopic versus open
cholecystectomy: a prospective analysis of 228 consecutive patients. Am Surg 1993; 59:23-7.
388. Kellosalo J, Alavaikko M, Laitinen. Effect of biliary tract procedures on duodenogastric reflux and the gastric mucosa. Scand J
Gastroenterol 1991;26:1272-8.
389. Kelly TR. Gallstone pancreatitis: The timing of surgery. Surgery 1980;88:345-50.
390. Kelly TR, Wagner DS. Gallstone pancreatitis: A prospective randomized trial of the timing of surgery. Surgery 1988;
104:600-5.
391. Kerin MJ, Gorey TF. Biliary injuries in the laparoscopic era. Eur J Surg 1994; 160:195-201.
392. Kerlan RK Jr, LaBerge JM, Ring EJ. Percutaneous cholecystolithotomy: Preliminary experience. Radiology 1985;157:653-6.
393. Keskimäki I, Aro S, Teperi J. Regional variation in surgical procedure rates in Finland. Scand J Soc Med1994;22:132-8.
394. Khuroo MS, Mahajan R, Zargar SA, Javid G, Banday M. Endoscopic vs surgical drainage of biliary tract in acute pyogenic
cholangitis: a controlled study letter [see comments]. Indian J Gastroenterol 1989; 8:119
395. Khuroo MS, Mahajan R, Zargar SA, Javid G, Sapru S. Prevalence of biliary tract disease in India: a sonographic study in adult
population in Kashmir. Gut 1989; 30:201-5.
396. Khuroo MS, Zargar SA, Yattoo GN. Efficacy of nifedipine therapy in patients with sphincter of Oddi dysfunction:
a prospective, double-blind, randomized, placebo-controlled, cross over trial. Br J Clin Pharmacol 1992; 33:477-85.
397. Kiil J, Kruse A, Rokkjaer M. Large bile duct stones treated by endoscopic biliary drainage. Surgery 1989; 105:51-6.
398. Kimura K, Ido K, Taniguchi Y, et al. Prospective study of laparoscopic cholecystectomy in two hundred and fifty patients
[see comments]. Endoscopy 1992; 24:740-4.
399. Kimura T, Goto H, Takeuchi Y, et al. Intraabdominal contamination after gallbladder perforation during laparoscopic
cholecystectomy and its complications. Surg Endosc 1996; 10:888-91.
400. Kimura T, Kimura K, Suzuki K, et al. Laparoscopic cholecystectomy: the Japanese experience. Surg Laparosc Endosc 1993;
3:194-8.
401. Kitano S, Iso Y, Tomikawa M, Moriyama M, Sugimachi K. A prospective randomized trial comparing pneumoperitoneum and
U-shaped retractor elevation for laparoscopic cholecystectomy. Surg Endosc 1993; 7:311-4.
402. Kiviluoto T, Luukkonen P, Haapiainen R, Kruuna O, Kivilaakso E. Laparoscopic cholecystectomy for symptomatic gallstone
disease. Experience of the first 200 cases [see comments]. Ann Chir Gynaecol 1992; 81:343-8.
403. Ko ST, Airan MC. Review of 300 consecutive laparoscopic cholecystectomies: development, evolution, and results. Surg
Endosc 1991; 5:103-8.
404. Koch JP, Donaldson RM. A survey of food intolerances in hospitalized patients. N Engl J Med 1964;271:657-60
405. Kocher M, Herzog U, Schuppisser JP, Ackermann Ch, Tondelli P. Was leistet die chirurgie der cholelithiasis heute? Helv chir
Acta 1991;58:969-76.
406. Koivusalo AM, Kellokumpu I, Scheinin M, Tikkanen I, Halme L, Lindgren L. Randomized comparison of the neuroendocrine
response to laparoscopic cholecystectomy using either conventional or abdominal wall lift techniques. Br J Surg 1996;
83:1532-6.
180
407. Koivusalo AM, Kellokumpu I, Lindgren L. Gasless laparoscopic cholecystectomy: comparison of postoperative recovery with
conventional technique. Br J Anaesth 1996; 77:576-80.
408. Kono S, Kochi S, Ohyama S, Wakisaka A. Gallstones, serum lipids, and glucose tolerance among male officials of self-defense
forces in Japan. Dig Dis Sci 1988;33:839-44.
409. Konsten J, Gouma DJ, von Meyenfeldt MF, Menheere P. Long-term follow-up after open cholecystec-tomy. Br J Surg 1993;
80:100-2.
410. Koprulu G, Esen F, Pembeci K, Denkel T. Pulmonary mechanics during laparoscopic surgery. Adv Exp Med Biol 1996; 388:
411. Kozarek R, Gannan R, Baerg R, Wagonfeld J, Ball T. Bile leak after laparoscopic cholecystectomy. Diagnostic and therapeutic
application of endoscopic retrograde cholangiopancreatogrphy. Arch Intern Med 1992;152:1040-3.
412. Kruse A. Endoskopisk papillotomi og stenekstraktion som behandling af choledocholithiasis. Ugeskr Læg 1978;140:395-9.
413. Kruse A, Mathiasen MS. Endoskopisk retrograd kolangio-pancreatografi (ERCP). Hundrede undersøgelser. Ugeskr Læg
1976;138:971-7
414. Kraagg N, Thijs C, Knipschild P. Dyspepsia--how noisy are gallstones? A meta-analysis of epidemiologic studies of biliary
pain, dyspeptic symptoms, and food intolerance. Scand J Gastroenterol 1995; 30:411-21.
415. Kullman E, Borch K, Dahlin LG, Liedberg G. Long-term follow-up of patients with gallbladder in situ after endoscopic
sphincterotomy for choledocholithiasis. Eur J Surg 1991; 157:131-5.
416. Kullman E, Borch K, Lindström E, Svanvik J, Anderberg B. Value of routine intraoperative cholangiography in detecting
aberrant bile ducts and bile duct injuries during laparoscopic cholecystectomy. Br J Surg 1996;83:171-5.
417. Kullman E, Dahlin LG, Hallhagen S, Segersvardh R, Borch K. Trends in incidence, clinical findings and outcome of acute and
elective cholecystectomy, 1970-1986. Eur J Surg 1994; 160:605-11.
418. Kum CK, Eypasch E, Lefering R, Paul A, Neugebauer E, Troidl H. Laparoscopic cholecystectomy for acute cholecystitis: is it
really safe? World J Surg 1996; 20:43-8.
419. Kum CK, Eypasch E, Aljaziri A, Troidl H. Randomized comparison of pulmonary function after the ’French’ and ’American’
techniques of laparoscopic cholecystectomy. Br J Surg 1996; 83:938-41.
420. Kum CK, Goh PM. Laparoscopic cholecystectomy: the Singapore experience. Surg Laparosc Endosc 1994; 4:22-4.
421.
Kunz R, Orth K, Vogel J, et al. Laparoscopic cholecystectomy versus mini-lap-cholecystectomy. Results of a prospective,
randomized study ([see comments]). Chirurg 1992; 63:291-5.
422. Ladocsi LT, Benitez LD, Filippone DR, Nance FC. Intraoperative cholangiography in laparoscopic cholecystectomy: a review of
734 consecutive cases. Am Surg 1997; 63:150-6.
423.
Lahtinen J, Alhava EM, Aukee S. Acute cholecystitis treated by early and delayed surgery. A controlled clinical trial. Scand J
Gastreoenterol 1978;13:673-8.
424. Lai EC, Mok FP, Tan ES, et al. Endoscopic biliary drainage for severe acute cholangitis [see comments]. N Engl J Med 1992;
326:1582-6.
425.
Laitinen J, Nuutinen L. Failure of transcutaneous electrical nerve stimulation and indomethacin to reduce opiate requirement
following cholecystectomy. Acta Anaesthesiol Scand 1991; 35:700-5.
426. Lam CM, Murray FE, Cuschieri A. Increased cholecystectomy rate after the introduction of laparoscopic cholecystectomy in
Scotland. Gut 1996; 38:282-4.
427. Lam D, Miranda R, Hom SJ. Laparoscopic cholecystectomy as an outpatient procedure. J Am Coll Surg 1997; 185:152-5.
428. Lane GE, Lathrop JC, Boysen DA, Lane RC. Effect of intramuscular intraoperative pain medication on narcotic usage after
laparoscopic cholecystectomy. Am Surg 1996; 62:907-10.
429. Langenbuch C. Ein Fall von Exstirpation der Gallenblase wegen chronischer Cholelithiasis: Heilung. Berliner Klin
Wochenschr 1882;19:725-7.
430. Lanzini A, Northfield TC. Pharmacological treatment of gallstones. Practical guidelines. Drugs 1994; 47:458-70.
181
431. Lanzini A, Northfield TC. Management of recurrent gallstones. Baillieres Clin Gastroenterol 1992; 6:767-83.
432. Larson GM, Vitale GC, Casey J, et al. Multipractice analysis of laparoscopic cholecystectomy in 1,983 patients. Am J Surg
1992; 163:221-6.
433. Leahy AL, Bouchier Hayes DB, Hyland JM, Delaney PV, O’Sullivan G, Keane FB. Early experiences of laparoscopic
cholecystectomy in five Irish hospitals. Irish Laparoscopic Group. Ir J Med Sci 1992; 161:410-3.
434. Leahy AL, Darzi AW, Murchan PM, et al. A safe new procedure for high-risk patients with symptomatic gallstones. Br J Surg
1991; 78:1319-20.
435. Ledet WP, Jr. Ambulatory cholecystectomy without disability. Arch Surg 1990; 125:1434-5.
436. Lee SH, Burhenne HJ. Persistence of symptoms after gall bladder clearance with cholecystolithotripsy [see comments].
Gut 1991; 32:536-8.
437. Lefering R, Troidl H, Ure BM. Do costs decide? Disposable or reusable instruments in laparoscopic cholecystectomy?
Chirurg 1994; 65:317-25.
438. Legorreta AP, Silber JH, Costantino GN, Kobylinski RW, Zatz SL. Increased cholecystectomy rate after the introduction of
laparoscopic cholecystectomy [see comments]. JAMA 1993; 270:1429-32.
439. Lehman GA, Sherman S. Sphincter of Oddi dysfunction. Int J Pancreatol 1996; 20:11-25.
440. Lennard TWJ, Farndon JR, Taylor RMR. Acalculous biliary pain: Diagnosis and selection for cholecystectomy using the
cholecystokinin test for pain reproduction. Br J Surg 1984;71:368-70.
441. Lennard TWJ, Farndon JR, Taylor RMR. Right upper quadrant pain and no gallstones: A clinical problem. Surv Dig Dis
1984;2:226-32.
442. Lenriot JP, Le Neel JC, Hay JM, Jaeck D, Millat B, Fagniez PL. Retrograde cholangiopancreatography and
endoscopic sphincterotomy for biliary lithiasis. Prospective evaluation in surgical circle. Gastroenterol Clin Biol 1993;
17:244-50.
443. Leung KL, Kwong KH, Lau WY, Chung SC, Li AK. Absorbable clips for cystic duct ligation in laparoscopic cholecystectomy.
Surg Endosc 1996; 10:49-51.
444. Leuschner U, Hellstern A, Ansell A, Gatzen M, Guldutuna S, Leuschner M. Manual and automatic gallstone dissolution with
methyl tert-butyl ether. Dig Dis Sci 1994; 39:1302-8.
445.
Leuschner U, Hellstern A, Guldutuna S, Gatzen M, Leuschner M. Direct contact dissolution of gallbladder stones with
methyl tert-butyl ether: experience in 209 patients. Z Gastroenterol Verh 1991; 26:
446. Leuschner U, Hellstern A, Schmidt K, et al. Gallstone dissolution with methyl tert-butyl ether in 120 patients – efficacy and
safety. Dig Dis Sci 1991; 36:193-9.
447.
Levesque RM. Immediate enteral feeding following cholecystectomy. J Am Coll Nutr 1982;1:388.
448. Levine SB, Lerner HJ, Leifer ED, Lindheim SR. Intraoperative cholangiography. A review of indications and analysis of age-sex
groups. Ann Surg 1983;198:692-7.
449. Lewis CE. Variation in the incidence of surgery. N Engl J Med 1969;281:880-4.
450. Lewis RT, Goodall RG, Marien B, Park M, Lloyd-Smith W, Wiegand FM. Simple elective cholecystecto-my: To drain or not.
Am J Surg 1990;159:241-5.
451. Liddle RA, Goldstein RB, Saxton J. Gallstone formation during weight-reduction dieting. Arch Intern Med 1989;149:1750-3.
452.
Lill H, Sitter H, Klotter HJ, Nies C, Guntert Gomann K, Rothmund M. What is the cost of laparoscopic cholecystectomy?
Chirurg 1992; 63:1041-4.
453. Lillemoe KD, Yeo CJ, Talamini MA, Wang BH, Pitt HA, Gadacz TR. Selective cholangiography. Current role in laparoscopic
cholecystectomy. Ann Surg 1992; 215:669-74.
454. Linden W van der, Edlund G. Early versus delayed cholecystectomy: The effect of a change in management. Br J Surg
1981;68:753-7.
182
455. Linden W van der, Sunzel H. Early versus delayed operation for acute cholecystitis. A controlled clinical trial. Am J Surg
1970;120:7-13.
456. Lindgren L, Koivusalo A-M, Kellokumpu I. Conventional pneumoperitoneum compared with abdominal wall lift for
laparoscopic cholecystectomy. Br J Anaesthesia 1995;75:567-72.
457. Lindlar R, Forster R, Krug D, Ballast A, Rothmund M. Laparoscopic cholecystectomy and continuing surgical education. Dtsch
Med Wochenschr 1991; 116:1777-82.
458. Litwin DE, Girotti MJ, Poulin EC, Mamazza J, Nagy AG. Laparoscopic cholecystectomy: trans-Canada experience with 2201
cases. Can J Surg 1992; 35:291-6.
459. Lo CY, Lai EC, Lo CM, et al. Endoscopic sphincterotomy: 7-year experience. World J Surg 1997; 21:67-71.
460. Loria P, Dilengite MA, Bozzoli M, et al. Prevalence rates of gallstone disease in Italy. The Chianciano population study. Eur J
Epidemiol 1994; 10:143-50.
461. Lorusso D, Misciagna G, Mangini V, et al. Duodenogastric reflux of bile acids, gastrin and parietal cells, and gastric acid
secretion before and 6 months after cholecystectomy. Am J Surg 1990; 159:575-8.
462. Lorusso D, Pezzolla F, Linsalata M, et al. Duodenogastric reflux and gastric mucosal cell proliferation after cholecystectomy or
Billroth II gastric resection. Gastroenterol Clin Biol 1994; 18:927-31.
463. Lorusso D, Pezzolla F, Messa C, et al. Cholecystectomy and duodenogastric reflux. Minerva Chir 1992; 47:1771-5.
464. Lorusso D, Pezzolla F, Cavallini A, et al. A prospective study on duodenogastric reflux and on histological changes in gastric
mucosa after cholecystectomy. Gastroenterol Clin Biol 1992; 16:328-33.
465. Lu SN, Chang WY, Wang LY, et al. Risk factors for gallstones among Chinese in Taiwan. A community sonographic survey. J
Clin Gastroenterol 1990; 12:542-6.
466. Lujan Mompean JA, Robles Campos R, Parrilla Paricio P, Liron Ruiz R, Torralba Martinez JA, Cifuentes Tebar J. Duodenogastric
reflux in patients with biliary lithiasis before and after cholecystecto-my. Surg Gynecol Obstet 1993; 176:116-8.
467. Lujan Mompean JA, Torralba Martinez JA, Parrilla Paricio P, Robles Campos R, Liron Ruiz R, Ramirez Romero P. Quantification
of duodenogastric reflux in patients with choledochoduodenostomy. J Am Coll Surg 1994; 179:193-6.
468. Luman W, Adams WH, Nixon SN, et al. Incidence of persistent symptoms after laparoscopic cholecystectomy: a prospective
study. Gut 1996; 39:863-6.
469. Lund J. Surgical indications in cholelithiasis: Prophylactic cholecystectomy elucidated on the basis of long-term follow up on
526 nonoperated cases. Ann Surg 1960;151:153-62.
470.
Macintyre IM, Wilson RG. Impact of laparoscopic cholecystectomy in the UK: a survey of consultants. Br J Surg 1993; 80:346
471. Macintyre IMC, Wilson RG. Laparoscopic cholecystectomy. Br J Surg 1993; 80:552-9.
472.
Mackey WA. Cholecystitis without stones. Br J Surg 1934;22:274-95.
473. Mackie CR, Wood RAB, Preece PE, Cuschieri A. Surgical pathology at early elective operation for suspected acute gallstone
pancreatitis: preliminary report of a prospective clinical trial. Br J Surg 1985;72:179-81.
474. MacMathuna P, White P, Clarke E, Lennon J, Crowe. Endoscopic sphincteroplasty: A novel and safe alternative to papillotomy
in the management of bile duct stones. Gut 1994;35:127-9.
475. Maddern GJ, Baxter PS. The effect of laparoscopic cholecystectomy on gastroduodenal reflux. Aust N Z J Surg 1997;
67:703-5.
476. Madhavan KK, Macintyre IM, Wilson RG, Saunders JH, Nixon SJ, Hamer Hodges DW. Role of intraoperative cholangiography
in laparoscopic cholecystectomy. Br J Surg 1995; 82:249-52.
477. Madsen CM, Sørensen HR, Truelsen F. The frequency of operative bile duct injuries, illustrated by a Danish county survey.
Acta Chir Scand 1960;119:110-1.
478. Madsen M, Andersen TF, Roepstorff C, Jørgensen S, Keskimäki I, Johnsson M, Paulson E, Nielsen HB. Rates of surgery in the
Nordic countries. Variation between and within nations. Nordic Medico-Statistical Committee NOMESCO 43:1994. DIKE.
183
479. Madsen PER, Ander JF, Jensen KB, Andersen D. Kolecystokinin-kolecystografi og kolecystokinin smerteprovokationstest.
Ugeskr Læg 1981;143:2968-70.
480. Madsen PV, Christensen T. Arbejdsfravær efter abdominalkirurgi. Ugeskr læg 1985;147:706-7.
481. Majeed AW, Reed MW, Watkin DF, Smart JG, Johnson AG. Sheffield cholecystoscope: new instrument for minimally invasive
gallbladder surgery. Br J Surg 1991; 78:557-8.
482. Majeed AW, Reed MW, Ross B, Peacock J, Johnson AG. Gallstone removal with a modified cholecystoscope: an alternative to
cholecystectomy in the high-risk patient. J Am Coll Surg 1997; 184:273-80.
483. Majeed AW, Troy G, Nicholl JP, Smythe A, Reed MWR, Stoddard CJ, Peacock J, Johnson AG. Randomised, prospective,
single-blind comparison of laparoscopic versus small-incision cholecystec-tomy. Lancet 1996;347:989-94.
484. Makino I, Shinozaki K, Yoshino K, Nakagawa S. Dissolution of cholesterol gallstones by ursodeoxycho-lic acid. Jap J Gastroenterol 1975;72:690-702.
485. Malet PF. Medical dissolution of gallstones with bile salts. Semin Roentgenol 1991; 26:239-44.
486. Manger T, Wolff H. Experiences and results in 200 laparoscopic cholecystectomies. Zentralbl Chir 1991; 116:1173-9.
487. Manji N, Bistrian BR, Mascioli EA, Benotti PA, Blackburn GL. Gallstone disease in patients with severe short bowel syndrome
dependent on parenteral nutrition. JPEN J Parenter Enteral Nutr 1989; 13:461-4.
488. Marotta F, Hada R, Morello P, et al. ERCP in the assessment of patients with post-cholecystectomy syndrome: benefits and
limitations. Neth J Med 1989; 35:232-40.
489. Marshall D, Hailey D, Hirsch N, Clark E, Menon D. The introduction of laparoscopic cholecystectomy in Canada and Australia.
Canadian Coordinating Office for Health Technology Assessment 1994. ISBN 1 895561 21 3.
490. Maruszynski M, Pojda Z. Interleukin 6 (IL-6) levels in the monitoring of surgical trauma. A comparison of serum IL-6
concentrations in patients treated by cholecystectomy via laparotomy or laparoscopy. Surg Endosc 1995;9:882-5.
491. Matzen P, Haubek A. Endoskopisk retrograd kolangio-pankreatografi (ERCP). Beskrivelse af en diagnostisk metodes
indkøringsfase. Ugeskr Læg 1978;140:404-7.
492. Maurer KR, Everhart JE, Ezzati TM, et al. Prevalence of gallstone disease in Hispanic populations in the United States
published erratum appears in Gastroenterology 1989 Jun;96(6):1630. Gastroen-terology 1989; 96:487-92.
493. May GR, Sutherland LR, Shaffer EA. Efficacy of bile acid therapy for gallstone dissolution: a meta-analysis of randomized
trials. Aliment Pharmacol Ther 1993; 7:139-48.
494. May GR, Shaffer EH. Should elective endoscopic sphincterotomy replace cholecystectomy for the treatment of high-risk
patients with gallstone pancreatitis? editorial [see comments]. J Clin Gastroenterol 1991; 13:125-8.
495. Mayer AD, McMahon MJ, Benson EA, Axon ATR. Operations upon the biliary tract in patients with acute pancreatitis: aims,
indications and timing. Ann Royal Coll Surg Eng 1984;66:179-83.
496. Mayo WJ. “Innocent” gallstones a myth. JAMA 1911;61:1021-4.
497. McArthur P, Cusschieri A, Sells RA, Shields R. Controlled clinical trial comparing early with interval cholecystectomy for acute
cholecystitis. Br J Surg 1975;62:850-2.
498. McDermott VG, Arger P, Cope C. Gallstone recurrence and gallbladder function following percutaneous cholecystolithotomy.
J Vasc Interv Radiol 1994; 5:473-8.
499. McGahan JP, Lindfors KK. Percutaneous cholecystostomy: an alternative to surgical cholecystostomy for acute cholecystitis?
Radiology 1989; 173:481-5.
500. McGinn FP, Miles AJG, Uglow M, Ozmen M, Terzi C, Humby M. Randomized trial of laparoscopic cholecystectomy and
minicholecystectomy. Br J Surg 1995;82:1374-7.
501. McIntyre RC, Jr., Zoeter MA, Weil KC, Cohen MM. A comparison of outcome and cost of open vs. laparoscopic
cholecystectomy. J Laparoendosc Surg 1992; 2:143-8.
184
502. McMahon AJ, Fullarton G, Baxter JN, O’Dwyer PJ. Bile duct injury and bile leakage in laparoscopic cholecystectomy. Br J Surg
1995; 82:307-13.
503. McMahon AJ, Russell IT, Ramsay G, et al. Laparoscopic and minilaparotomy cholecystectomy: a randomized trial comparing
postoperative pain and pulmonary function. Surgery 1994; 115:533-9.
504.
McMahon AJ, Russell IT, Baxter JN, et al. Laparoscopic versus minilaparotomy cholecystectomy: a randomised trial
[see comments]. Lancet 1994; 343:135-8.
505. McMahon AJ, Ross S, Baxter JN, Russell IT, Anderson JR, Morran CG, Sunderland GT, Galloway DJ, O’Dwyer PJ. Symptomatic
outcome 1 year after laparoscopic and minilaparotomy cholecystectomy: A randomized trial. Br J Surg 1995;82:1378-82.
506. McNulty J, Chua A, Keating J, Ah Kion S, Weir DG, Keeling PW. Dissolution of cholesterol gall stones using methyltertbutyl
ether: a safe effective treatment. Gut 1991; 32:1550-3.
507. McPherson K, Strong PM, Jones L. Britton BJ. Do cholecystectomy rates correlate with geographic variations in the
prevalence of gallstones? J Epidemiol Commun Health 1985;39:179-82.
508. McSherry CK, Ferstenberg H, Calhoun F, Lahman E, Virshup M. The natural history of diagnosed gallstone disease in
symptomatic and asymptomatic patients. Ann Surg 1985;202:59-63.
509. Meijer DW, Rademaker BP, Schlooz S, et al. Laparoscopic cholecystectomy using abdominal wall retraction. Hemodynamics
and gas exchange, a comparison with conventional pneumoperitoneum. Surg Endosc 1997; 11:645-9.
510. Meijer WS. Gallbladder extirpation in The Netherlands; frequency, surgical mortality and postoperative complications
(1987-1989). Ned Tijdschr Geneeskd 1991; 135:1688-91.
511. Mellström D, Asztély M, Svanvik J. Gallstones and previous cholecystectomy in 77- to 78-year-old women in an urban
population in Sweden. Scand J Gastroenterol 1988;23:1241-4.
512. Mentha G, Vettorel D, Meyer P, Klopfenstein CE, Rohner A. Results of biliary surgery in a teaching center. Schweiz Med
Wochenschr 1990; 120:226-30.
513.
Merrie AE, Booth MW, Shah A, Pettigrew RA, McCall JL. Bile duct imaging and injury: a regional audit of laparoscopic
cholecystectomy. Aust N Z J Surg 1997; 67:706-11.
514. Merrill JR. Minimal trauma cholecystectomy (A “No-Touch” procedure in a “Well”). Am Surg 1988;54:256-61.
515. Messahel FM. Post cholecystectomy admission to the intensive care unit. Comparison between open, mini-lap and
laparoscopic techniques. Anaesthesia 1995;50:901-4.
516. Metzger J, Muller C. 1-year follow-up of laparoscopic cholecystectomy in an unselected patient sample. Objective findings
and subjective status. Helv Chir Acta 1994; 60:767-72.
517. Meyenberger C, Meierhofer U, Michel Harder C, et al. Long-term follow-up after treatment of common bile duct stones by
extracorporeal shock-wave lithotripsy. Endoscopy 1996; 28:411-7.
518. Meyer C, De Manzini N, Rohr S, Thiry CL, Perim Kalil FC, Bachellier Billot C. 1000 cases of cholecystectomy: 500 by laparotomy versus 500 by laparoscopy. J Chir Paris 1993; 130:501-6.
519. Michaloliakou C, Chung F, Sharma S. Preoperative multimodal analgesia facilitates recovery after ambulatory laparoscopic
cholecystectomy. Anesth Analg 1996; 82:44-51.
520. Middleton GW, Williams JH. Is gall bladder ejection fraction a reliable predictor of acalculous gall bladder disease?
[see comments]. Nucl Med Commun 1992; 13:894-6.
521.
Miles RH, Carballo RE, Prinz RA, et al. Laparoscopy: the preferred method of cholecystectomy in the morbidly obese.
Surgery 1992; 112:818-22.
522. Milheiro A, Sousa FC, Manso EC, Leitao F. Metabolic responses to cholecystectomy: open vs. laparoscopic approach
[see comments]. J Laparoendosc Surg 1994; 4:311-7.
523. Millat B, Atger J, Deleuze A, et al. Laparoscopic treatment for choledocholithiasis: a prospective evaluation in 247
consecutive unselected patients. Hepatogastroenterology 1997; 44:28-34.
524. Mjaland O, Raeder J, Aasboe V, Trondsen E, Buanes T. Outpatient laparoscopic cholecystectomy. Br J Surg 1997; 84:958-61.
185
525. Monson JRT, Guillou PJ, Keane FBV, Tanner WA, Brennan TG. Cholecystectomy is safer without drainage: The results of a
prospective, randomized clinical trial. Surgery 1991;109:740-6.
526. Moore MJ, Bennett CL. The learning curve for laparoscopic cholecystectomy. The Southern Surgeons Club. Am J Surg 1995;
170:55-9.
527. Morgan R, Lauffer G, Northfield T, Grundy A. Radiological aspects of solvent dissolution of gall-stones. Clin Radiol 1993;
48:172-5.
528. Morgenstern L, McGrath MF, Carroll BJ, Paz-Partlow M, Berci G. Continuing hazards of the learning curve in laparoscopic
cholecystectomy. Am Surg 1995;61:914-8.
529. Morgenstern L, Wong L, Berci G. Twelve hundred open cholecystectomies before the laparoscopic era. A standard for
comparison. Arch Surg 1992; 127:400-3.
530. Morino M, Festa V, Garrone C. Survey on Torino courses. The impact of a two-day practical course on apprenticeship and
diffusion of laparoscopic cholecystectomy in Italy. Surg Endosc 1995; 9:46-8.
531. Mort EA, Guadagnoli E, Schroeder SA, et al. The influence of age on clinical and patient-reported outcomes after
cholecystectomy. J Gen Intern Med 1994; 9:61-5.
532. Morton CE. Cost containment with the use of “mini-cholecystectomy” and intraoperative cholangio-graphy. Am Surg
1985;51:168-9.
533. Moss G. Discharge within 24 hours of elective cholecystectomy. Arch Surg 1986;121:1159-61. (a)
534. Moss G. Mini-trauma cholecystectomy. J Abdominal Surg 1983;25:66-74.
535. Moss G. Raising the outcome standards for conventional open cholecystectomy. Am J Surg 1996; 172:383-5.
536. Moss G, Regal ME, Lichtig L. Reducing postoperative pain, narcotics, and length of hospitalization. Surgery 1986;99:206-10.
(b)
537. Mraovic B, Jurisic T, Kogler Majeric V, Sustic A. Intraperitoneal bupivacaine for analgesia after laparoscopic cholecystectomy.
Acta Anaesthesiol Scand 1997; 41:193-6.
538. Mucio M, Felemovicius J, De la Concha F, Cabello R, Zamora A. The Mexican experience with laparoscopic cholecystectomy
and common bile duct exploration. A multicentric trial. Surg Endosc 1994; 8:306-9.
539. Muhrbeck O, Ahlberg J. Prevalence of gallstone disease in a Swedish populatio. Scand J Gastroenterol 1995;30:1125-8.
540. Muhrbeck O, Sahlin S, Ahlberg J. Rise and fall in the number of cholecystectomies: Stockholm 1932-1993. Eur J Surg 1996;
162:199-204.
541. Muller GP. The noncalculous gall-bladder. JAMA 1927;89:786-9.
542. Munster AM, Brown JR. Acalculous cholecystitis. Am J Surg 1967;113:730-4.
543. Murison MS, Gartell PC, McGinn FP. Does selective peroperative cholangiography result in missed common bile duct
stones? J R Coll Surg Edinb 1993; 38:220-4.
544. Murray WR, Laferla G, Fullarton GM. Choledocholithiasis – in vivo stone dissolution using methyl tertiary butyl ether (MTBE).
Gut 1988;29:143-5.
545. Mühe E. Die erste Cholecystektomie durch das laparoskop. Langenbecks Archiv für Chirurgie 1986;369:804.
546. Mühe E. Laparoscopic cholecystectomy – late results. Langenbecks Arch Chir Suppl Kongressbd 1991;
547. Mühe E. Long-term follow-up after laparoscopic cholecystectomy. Endoscopy 1992; 24:754-8.
548. Nagorney DM, Lohmuller JL. Choledochoscopy. A cost-minimization analysis. Ann Surg 1990; 211:354-9.
549. Nano M, Palmas F, Giaccone M, et al. Biliary reflux after cholecystectomy: a prospective study. Hepatogastroenterology 1990;
37:233-4.
550. Nassif AC. Peri-operative accelerated recovery technique (art) with Moss feeding-decompression regimen. J Am Coll Nutr
1984;3:281.
186
551. Nechis M, King CM, Murphy RA. Cholecystokinin cholecystography in the diagnosis of acalculous extrahepatic biliary tract
disorders. Am J Gastroenterol 1978;70:593-9.
552. Nel CJ, Grobler SP. Management of acute calculous cholecystitis. Surg Annu 1991; 23 Pt 1:
553. Nelson PE, Moyer TP, Thistle JL. Dissolution of calcium bilirubinate and calcium carbonate debris remaining after methyl tertbutyl ether dissolution of cholesterol gallstones. Gastroenterology 1990; 98:1345-50.
554. Nenner RP, Imperato PJ, Rosenberg C, Ronberg E. Increased cholecystectomy rates among Medicare patients after the
introduction of laparoscopic cholecystectomy. J Community Health 1994; 19:409-15.
555. Neoptolemos JP, Bailey IS, Carr-Locke DL. Sphincter of Oddi dysfunction: results of treatment by endoscopic
sphincterotomy. Br J Surg 1988a;75:454-9.
556. Neoptolemos JP, Carr-Locke DL, London NJ, Bailey IA, James D, Fossard DP. Controlled trial of urgent endoscopic retrograde
cholengiopancreatography and endoscopic sphincterotomy versus conservative treatment for acute pancreatitis due to
gallstones. Lancet 1988b;II:979-83.
557. Neoptolemos JP, Carr-Locke DL, Fossard DP. Prospective randomised study of preoperative endoscopic sphincterotomy
versus surgery alone for common bile duct stones. Br Med J 1987;294:470-4.
558. Neoptolemos JP, Carr-Locke DL, Fraser I, Fossard DP. The management of common bile duct calculi by endoscopic
sphincterotomy in patients with gallbladders in situ. Br J Surg 1984;71:69-71.
559. Neoptolemos JP, Hall C, O’Connor HJ, Murray WR, Carr Locke DL. Methyl-tert-butyl-ether for treating bile duct stones:
the British experience. Br J Surg 1990; 77:32-5.
560. Neoptolemos JP, London N, Slater ND, Carr-Locke DL, Fossard DP, Moosa AR. A prospective study of ERCP and endoscopic
sphincterotomy in the diagnosis and treatment of gallstone acute pancreatitis. A rational and safe approach to
management. Arch Surg 1986;121:697-702.
561. Neoptolemos JP, Shaw DE, Carr Locke DL. A multivariate analysis of preoperative risk factors in patients with common bile
duct stones. Implications for treatment. Ann Surg 1989; 209:157-61.
562. Neubrand M, Holl J, Sackmann M, et al. Combination of extracorporeal shock-wave lithotripsy and dissolution of
gallbladder stones with methyl tert-butyl ether: a randomized study. Hepatology 1994; 19:133-7.
563. Neuhaus H, Hoffmann W, Classen M. Laser lithotripsy of pancreatic and biliary stones via 3.4 mm and 3.7 mm miniscopes:
first clinical results. Endoscopy 1992; 24:208-14.
564. Newman HF, Northup JD, Rosenblum M, Abrams H. Complications of cholelithiasis 1968;50:476-96.
565. Nicholl JP, Brazier JE, Milner PC, et al. Randomised controlled trial of cost-effectiveness of lithotripsy and open
cholecystectomy as treatments for gallbladder stones. Lancet 1992; 340:801-7.
566. Nomura H, Kashiwagi S, Hayashi J, Kajiyama W, Ikematsu H, Noguchi A, Tani S, Goto M. Prevalence of gallstone disease in a
general population of Okinawa, Japan. Am J Epidemiol 1988;128:598-605.
567. Nora PF, Davis RP, Fernandez MJ. Chronic acalculous gallbladder disease: A clinical enigma. World J Surg 1984;8:106-12.
568. Norrby S, Herlin P, Holmin T, Sjödahl R, Tagesson C. Early or delayed cholecystectomy in acute cholecystitis? A clinical trial.
Br J Surg 1983;70:163-.
569. Nottle PD. Percutaneous laparoscopic cholecystectomy: indications, contraindications and complications. Aust N Z J Surg
1992; 62:188-92.
570. Nowak A, Nowakowska-Duzawa E, Rybicka J. Urgent endoscopic sphincterotomy vs. conservative treatment in acute biliary
pancreatitis – prospective controlled trial. Hepatogastroentology 1990;37(suppl II):A5.
571. Nudo R, Pasta V, Monti M, Vergine M, Picardi N. Correlation between “post-cholecystectomy sindrome” and biliary reflux
gastritis. Endoscopic study. Ann Ital Chir 1989;60:291-302.
572. Nurnberg D, Berndt H, Pannwitz H. Familial incidence of gallstones. Dtsch Med Wochenschr 1989; 114:1059-63.
573. O’Donnall LDJ, Heaton KW. Recurrence and re-recurrence of gall stones after medical dissolution: A longterm follow up.
Gut 1988;29:655-8.
187
574. O’Dwyer PJ, McGregor JR, McDermott EW, Murphy JJ, O’Higgins NJ. Patient recovery following cholecystectomy through a
6 cm or 15 cm transverse subcostal incision: a prospective randomized clinical trial. Postgrad Med J 1992; 68:817-9.
575. Oi I. Fiberduodenoscopy and endoscopic pancreato-cholangiography. Gastrointest Endosc 1970;17:59-62.
576. Opie EL. The etiology of acute hemorrhagic pancreatitis. Bull John Hopkins Hosp 1901;12:182.
577. Orlando R, 3d, Russell JC, Lynch J, Mattie A. Laparoscopic cholecystectomy. A statewide experience. The Connecticut
Laparoscopic Cholecystectomy Registry. Arch Surg 1993; 128:494-8.
578. Orlando R, Russell JC. Managing gallbladder disease in a cost-effective manner. Surg Clin North Am 1996; 76:117-28.
579. Ortega AE, Peters JH, Incarbone R, et al. A prospective randomized comparison of the metabolic and stress hormonal
responses of laparoscopic and open cholecystectomy. J Am Coll Surg 1996; 183:249-56.
580. O’Sullivan ST, Hehir DJ, O’Sullivan GC, Kirwan WO. Open common bile duct exploration – end of an epoch? I J M S
1996;165:32-4.
581. Ovaska J, Airo I, Haglund C, et al. Laparoscopic cholecystectomy: the Finnish experience. Ann Chir Gynaecol 1996; 85:208-11.
582. Oxman A. Preparing and maintaining systematic reviews. In: The Cochrane Collaboration Handbook 1994;VI:35.
583. Oxorn DC, Whatley GS. Post-cholecystectomy pulmonary function following interpleural bupivacaine and intramuscular
pethidine [see comments]. Anaesth Intensive Care 1989; 17:440-3.
584.
Page DW. Immediate enteral feeding and early discharge after cholecystectomy. J Am Coll Nutr 1983;2:310-1.
585. Palasciano G, Portincasa P, Vinciguerra V, et al. Gallstone prevalence and gallbladder volume in children and adolescents:
an epidemiological ultrasonographic survey and relationship to body mass index. Am J Gastroenterol 1989; 84:1378-82.
586. Paloyan D, Simonowitz D, Skinner DB. The timing of biliary tract operations in patients with pancreatitis associated with
gallstones. Surg Gyn Obst 1975;141:737-9.
587. Panton ON, Nagy AG, Scudamore CH, Panton RJ. Laparoscopic cholecystectomy: a continuing plea for routine
cholangiography. Surg Laparosc Endosc 1995; 5:43-9.
588. Paolucci V, Schaeff B, Gutt CN, Encke A. Disposable versus reusable instruments in laparoscopic cholecystectomy.
A prospective, randomised study. Endosc Surg Allied Technol 1995; 3:147-50.
589. Pasquale MD, Nauta RJ. Selective vs routine use of intraoperative cholangiography. An argument. Arch Surg 1989;
124:1041-2.
590. Pasqualucci A, Contardo R, Da Broi U, et al. The effects of intraperitoneal local anesthetic on analgesic requirements and
endocrine response after laparoscopic cholecystectomy: a randomized double-blind controlled study. J Laparoendosc Surg
1994; 4:405-12.
591. Pasqualucci A, de Angelis V, Contardo R, et al. Preemptive analgesia: intraperitoneal local anesthetic in laparoscopic
cholecystectomy. A randomized, double-blind, placebo-controlled study. Anesthesiology 1996; 85:11-20.
592. Patel JM, Lanzafame RJ, Williams JS, Mullen BV, Hinshaw JR. The effect of incisional infiltration of bupivacaine hydrochloride
upon pulmonary functions, atelectasis and narcotic need following elective cholecystectomy. Surg Gyn Obst 1983;
157:338-40.
593. Patti MG, Pellegrini CA. Gallstone pancreatitis. Surg Clin North Am 1990; 70:1277-95.
594. Paul A, Eypasch EP, Holthausen U, Troidl H. Bowel obstruction caused by a free intraperitoneal gallstone – a late
complication after laparoscopic cholecystectomy. Surgery 1995; 117:595-6.
595. Paul A, Troidl H, Gay K, Viell B, Bode C. Dyspepsia and food intolerance in symptomatic gallstone disease. Does cholecystectomy help? Chirurg 1991; 62:462-6.
596. Pauletzki J, Holl J, Sackmann M, et al. Gallstone recurrence after direct contact dissolution with methyl tert-butyl ether.
Dig Dis Sci 1995; 40:1775-81.
597. Peine CJ, Petersen BT, Williams HJ, et al. Extracorporeal shock-wave lithotripsy and methyl tert-butyl ether for partially
calcified gallstones. Gastroenterology 1989; 97:1229-35.
188
598. Pelissier EP, Blum D, Meyer JM, Girard JF. Cholecystectomy by minilaparotomy without muscle section: a short-stay
procedure. Hepatogastroenterology 1992; 39:294-5.
599. Peng NJ, Lai KH, Tsay DG, Liu RS, Su KL, Yeh SH. Efficacy of quantitative cholescintigraphy in the diagnosis of sphincter of
Oddi dysfunc tion. Nucl Med Commun 1994; 15:899-904.
600. Perdikis G, Wilson P, Hinder R, et al. Altered antroduodenal motility after cholecystectomy. Am J Surg 1994; 168:609-14.
601. Perissat J, Collet DR, Belliard R. Gallstones: Laparoscopic treatment, intracorporeal lithotripsy followed by cholecystostomy or
cholecystectomy – a personal technique. Endoscopy 1989;21:373-4.
602. Perissat J, Collet D, Edye M, Magne E, Belliard R, Desplantez J. Laparoscopic cholecystectomy: an analysis of 777 cases.
Baillieres Clin Gastroenterol 1992; 6:727-42.
603. Pers M, Baden H. On the frequency of recurrence of calculi in the gall bladder after cholecystolithoto-my. Acta Chir Scand
1951;102:260-6.
604. Persson G, Sloth M, Skold S, Thulin A. Evaluation of anamnestic data in patients referred for oral cholecystography. Scand J
Gastroenterol 1989; 24:550-6.
605. Persson GE, Thelin AG, Thulin AJ. Changes in the surgical treatment of gallstones during a 10 year period. Eur J Surg 1993;
159:409-13.
606. Peters JH, Ellison EC, Innes JT, et al. Safety and efficacy of laparoscopic cholecystectomy. A prospective analysis of 100 initial
patients [see comments]. Ann Surg 1991; 213:3-12.
607. Peters JH, Gibbons GD, Innes JT, et al. Complications of laparoscopic cholecystectomy. Surgery 1991; 110:769-77.
608. Peterson R. Gall-stones during the course of 1,066 abdominal sections for pelvic disease. Surg Gyn Obst 1915;20:284-91.
609. Picus D, Hicks ME, Darcy MD, et al. Percutaneous cholecystolithotomy: analysis of results and complications in 58 consecutive
patients. Radiology 1992; 183:779-84.
610. Pilpel D, Fraser GM, Kosecoff J, Weitzman S, Brook RH. Regional differences in appropriateness of cholecystectomy in a
prepaid health insurance system. Public Health Rev 1992; 20:61-74.
611. Pixley F, Mann J. Dietary factors in the aetiology of gallstones: a case control study. Gut 1988;29:1511-5.
612. Pixley F, Wilson D, McPherson K, Mann J. Effect of vegetarianism on development of gall stones in women. BMJ
1985;291:11-12.
613. Plaisier PW, Berger MY, van der Hul RL, et al. Unexpected difficulties in randomizing patients in a surgical trial: a prospective
study comparing extracorporeal shock wave lithotripsy with open cholecystectomy. World J Surg 1994; 18:769-72.
614. Plaisier PW, van der Hul RL, Nijs HG, den Toom R, Terpstra OT, Bruining HA. The course of biliary and gastrointestinal
symptoms after treatment of uncomplicated symptomatic gallstones: results of a randomized study comparing
extracorporeal shock wave lithotripsy with conventional cholecystecto-my. Am J Gastroenterol 1994; 89:739-44.
615. Plaisier PW, van der Hul RL, Nijs HG, den Toom R, Terpstra OT, Bruining HA. Quality of life after treatment of gallstones:
results of a randomised study of lithotripsy and open cholecystectomy. Eur J Surg 1994; 160:613-7.
616. Ponce J, Cutshall KE, Hodge MJ, Browder W. The lost laparoscopic stone. Potential for long-term complications. Arch Surg
1995; 130:666-8.
617. Ponchon T, Gagnon P, Valette PJ, Henry L, Chavaillon A, Thieulin F. Pulsed dye laser lithotripsy of bile duct stones.
Gastroenterology 1991; 100:1730-6.
618. Pongchairerks P. The impact of laparoscopic cholecystectomy on the practice and training of gallbladder surgery in
Thailand. Ann Acad Med Singapore 1996; 25:629-34.
619. Prasad A, Foley RJ. Day case laparoscopic cholecystectomy: a safe and cost effective procedure. Eur J Surg 1996; 162:43-6.
620. Price WH. Gall-bladder dyspepsia. BMJ 1963;2:138-41.
621. Putensen Himmer G, Putensen C, Lammer H, Lingnau W, Aigner F, Benzer H. Comparison of postoperative respiratory
function after laparoscopy or open laparotomy for cholecystectomy. Anesthesiology 1992; 77:675-80.
189
622. Qureshi MA, Burke PE, Brindley NM, et al. Post-cholecystectomy symptoms after laparoscopic cholecystectomy
[see comments]. Ann R Coll Surg Engl 1993; 75:349-53.
623. Radder RW. Ultrasonically guided percutaneous catheter drainage for gallbladder empyema. Diagn Imaging (Basel)
1980;49:330-3.
624. Rademaker BM, Kalkman CJ, Odoom JA, de Wit L, Ringers J. Intraperitoneal local anaesthetics after laparoscopic
cholecystectomy: effects on postoperative pain, metabolic responses and lung function. Br J Anaesth 1994; 72:263-6.
625. Rademaker BM, Sih IL, Kalkman CJ, et al. Effects of interpleurally administered bupivacaine 0.5% on opioid analgesic
requirements and endocrine response during and after cholecystectomy: a randomized double-blind controlled study.
Acta Anaesthesiol Scand 1991; 35:108-12.
626. Raetzell M, Maier C, Schröder D, Wulf H. Intraperitoneal application of bupivacaine during laparoscopic cholecystectomy –
risk or benefit? Anesth Analg 1995;81:967-72.
627. Raine PAM, Gunn AA. Acute cholecystitis. Br J Surg 1975;62:697-99.
628. Rajagopalan AE, Pickleman J. Biliary colic and functional gallbladder disease. Arch Surg 1982;117:1005-8.
629. Ralston DE, Smith LA. The natural history of cholelithiasis. Minn Med 1965;48:327-32.
630. Ransohoff DF, Gracie WA. Management of patients with symptomatic gallstones: a quantitative analysis. Am J Med 1990;
88:154-60.
631. Ransohoff DF, Gracie WA, Wolfenson LB, Neuhauser D. Prophylactic cholecystectomy or expectant management for persons
with silent gallstones: A decision analysis to assess survival. Ann Int Med 1983;99:199-204.
632. Ranson JHC. The timing of biliary surgery in acute pancreatitis. Ann Surg 1979;189:654-63.
633. Ratliff DS, Denning DA, Canterbury TD, Walker JT. Laparoscopic cholecystectomy: a community experience. South Med J
1992; 85:942-5.
634. Redmond HP, Watson RW, Houghton T, Condron C, Watson RG, Bouchier Hayes D. Immune function in patients undergoing
open vs laparoscopic cholecystectomy. Arch Surg 1994; 129:1240-6.
635. Regal ME, Lichtig LK. Immediate & sustained nutrition leads to safe early discharge after cholecystec-tomy. J Am Coll Nutr
1983;2:319.
636. Regoly Merei J, Ihasz M. Bile duct injuries in laparoscopic cholecystectomy. A computerized analysis of 148 lesions in 24,440
operations in 89 Hungarian institutes (publication by the Hungarian Society of Surgery). Langenbecks Arch Chir Suppl Kongressbd 1996; 113:
637. Reid DRK, Rogers IM, Calder JF. The cholecystokinin test;: An assessment Br J Surg 1975;62:317-9.
638. Reiss R, Nudelman I, Gutman C, Deutsch AA. Changing trends in surgery for acute cholecystitis [see comments]. World J
Surg 1990; 14:567-70.
639. Reshetnikov EA, Denisova AL. Clinical course of asymptomatic cholecystolithiasis. Khirurgiia Mosk 1993; 3-7.
640. Rhind JA, Watson L. Gall stone dyspepsia. BMJ 1968;1:32.
641.
Rhodes M, Lennard TWJ, Farndon JR, Taylor RMR. Cholecystokinin (CCK) provocation test: long-term follow-up after
cholecystectomy. Br J Surg 1988;75:951-3.
642. Richardson MC, Bell G, Fullarton GM. Incidence and nature of bile duct injuries following laparoscopic cholecystectomy:
an audit of 5913 cases. West of Scotland Laparoscopic Cholecystectomy Audit Group. Br J Surg 1996; 83:1356-60.
643. Rigas B, Torosis J, McDougall CJ, Vener KJ, Spiro HM. The circadian rhythm of biliary colic [see comments]. J Clin
Gastroenterol 1990; 12:409-14.
644. Roberts-Thomson IC, Toouli J. Is endoscopic sphincterotomy for disabling biliary-type pain after cholecystectomy
effective? Gastrointestinal endoscopy 1985;31:370-3.
645. Roesel RW. Experience with mini-invasive endoscopic removal of gallstones. Surg Endosc 1989; 3:124-5.
190
646. Rogy MA, Fugger R, Herbst F, Schulz F. Reoperation after cholecystectomy. The role of the cystic duct stump. HPB Surg 1991;
4:129-34.
647. Rolny P, Geenen JE, Hogan WJ. Post-cholecystectomy patients with “objective signs” of partial bile outflow obstruction:
clinical characteristics, sphincter of Oddi manometry findings, and results of therapy. Gastrointest Endosc 1993; 39:778-81.
648. Roos LL, Roos NP, Sharp SM. Monitoring adverse outcomes of surgery using administrative data. Health Care Finan Rew.
Annual supplementum 1987:5-16.
649. Ros E, Zambon D. Postcholecystectomy symptoms. A prospective study of gallstone patients before and two years after
surgery. Gut 1987;28:1500-4.
650. Ross WB, Tweedie JH, Leong YP, Wyman A, Smithers BM. Intercostal blockade and pulmonary function after
cholecystectomy. Surgery 1989; 105:166-9.
651. Rothenbuhler JM, Chevalley JP, Famos M. Postcholecystectomy syndrome after simple cholecystec-tomy. Helv Chir Acta
1989; 56:175-8.
652. Rothlin MA, Schlumpf R, Largiader F. Laparoscopic sonography. An alternative to routine intraoperative cholangiography?
Arch Surg 1994; 129:694-700.
653. Rothwell JF, Lawlor P, Byrne PJ, Walsh TN, Hennessy TP. Cholecystectomy-induced gastroesopha-geal reflux: is it reduced by
the laparoscopic approach? Am J Gastroenterol 1997; 92:1351-4.
654. Rovina N, Bouros D, Tzanakis N, et al. Effects of laparoscopic cholecystectomy on global respiratory muscle strength. Am J
Respir Crit Care Med 1996; 153:458-61.
655. Rozsos I, Rozsos T. The applicability of micro- and minilaparotomy in the management of obstructive cholecystitis. Acta Chir
Hung 1994; 34:95-101.
656. Rozsos I, Rozsos T. Micro- and modern minilaparotomy cholecystectomy. Acta Chir Hung 1994; 34:11-6.
657. Ruppin DC, Dowling RH. Is recurrence inevitable after gallstone dissolution by bile-acid treatment? Lancet 1982;i:181-5.
658. Russell JC, Walsh SJ, Mattie AS, Lynch JT. Bile duct injuries, 1989-1993. A statewide experience. Connecticut Laparoscopic
Cholecystectomy Registry. Arch Surg 1996; 131:382-8.
659. Russell WC, Ramsay AH, Fletcher DR. The effect of incisional infiltration of bupivacaine upon pain and respiratory function
following open cholecystectomy [see comments]. Aust N Z J Surg 1993; 63:756-9.
660.
Rutledge R. Can medical school-affiliated hospitals compete with private hospitals in the age of managed care? An 11-state,
population-based analysis of 351,201 patients undergoing cholecystecto-my [see comments]. J Am Coll Surg 1997;
185:207-17.
661. Saadah HA. Post-cholecystectomy biliary pain and dyspepsia (response to 3-hydroxy-3-methylglutaryl coenzyme A
reductase inhibitors). J Okla State Med Assoc 1994; 87:315-8.
662. Sackier JM, Berci G, Phillips E, Carroll B, Shapiro S, Paz Partlow M. The role of cholangiography in laparoscopic
cholecystectomy. Arch Surg 1991; 126:1021-5.
663. Sackmann M. Gallbladder stones: shockwave therapy. Baillieres Clin Gastroenterol 1992; 6:697-714.
664. Sackmann M, Niller H, Klueppelberg U, et al. Gallstone recurrence after shock-wave therapy [see comments].
Gastroenterology 1994; 106:225-30.
665. Sackmann M, Pauletzki J, Sauerbruch T, Holl J, Schelling G, Paumgartner G. The Munich Gallbladder Lithotripsy Study.
Results of the first 5 years with 711 patients. Ann Intern Med 1991; 114:290-6.
666. Safatle NF, da Costa Filho J, Ciasca DV, Ribeiro AV. Cholecystectomy using median minilaparotomy. A new method.
Arq Gastroenterol 1991; 28:119-23.
667. Safran DB, Sullivan BS, Leveque JE, Williams MD. Cholecystectomy following the introduction of laparoscopy: more, but for
the same indication. Am Surg 1997; 63:506-11.
668. Safrany L, Neuhaus B, Krause S, Portocarrero G, Schott B. Endoskopische Papillotomie bei akuter, biliär bedingter
Pankreatitis. Dtsch Med Wochenschr 1980;105:115-9.
191
669. Salamon V, Simunic S, Radanovic B. Percutaneous transhepatic dissolution of gallbladder stones. Z Gastroenterol 1992;
30:459-62.
670. Salembier MY. Présentation ’une technique de cholécystostomie par une incision minime. Lille-Chir 1955;10:16-22.
671. Salembier Y. Cholécystectomie par une courte incision transversale. Press Med 1986;15:210-1.
672. Salen G, Tint GS, Shefer S. Treatment of cholesterol gallstones with litholytic bile acids. Gastroenterol Clin North Am 1991;
20:171-82.
673. Salim AS. Percutaneous aspiration, lavage and antibiotic instillation. New approach in the management of acute calculous
cholecystitis. HPB Surg 1991; 3:167-75.
674. Saltzstein EC, Mercer LC, Peacock JB, Dougherty SH. Twenty-four hour hospitalization after cholecystectomy. Surg Gyn Obst
1991;173:367-70.
675.
Saltzstein EC, Mercer LC, Peacock JB, Dougherty SH. Outpatient open cholecystectomy. Surg Gynecol Obstet 1992; 174:
173-5.
676. Sama C, Labate AM, Taroni F, Barbara L. Epidemiology and natural history of gallstone disease. Semin Liver Dis 1990;
10:149-58.
677. Sampliner RE, Bennett PH, Comess LJ, Rose FA, Burch TA. Gallbladder disease in Pima indians. Demonstration of high
prevalence and early onset by cholecystography. N Engl J Med 1970;283:1358-64.
678. Sand J, Nordback I, Koskinen M, Matikainen M, Lindholm TS. Nifedipine for suspected type II sphincter of Oddi dyskinesia
[see comments]. Am J Gastroenterol 1993; 88:530-5.
679. Sarac AM, Aktan AO, Baykan N, Yegen C, Yalin R. The effect and timing of local anesthesia in laparoscopic cholecystectomy.
Surg Laparosc Endosc 1996; 6:362-6.
680. Sauerbruch T, Delius M, Holl J et al. Fragmentation of gallstones in humans by extracorporal shock wave treatment.
Hepatology 1985;5:977.
681.
Schauer PR, Luna J, Ghiatas AA, Glen ME, Warren JM, Sirinek KR. Pulmonary function after laparoscopic cholecystectomy.
Surgery 1993; 114:389-97.
682. Schauer PR, Page CP, Stewart RM, Schwesinger WH, Sirinek KR. The effect of laparoscopic cholecystectomy on resident
training. Am J Surg 1994; 168:566-9.
683. Scheel V. Undersøgelser over cholelithiasis. Ugeskr Læg 1911;73:1757-74.
684. Scheinin B, Kellokumpu I, Lindgren L, Haglund C, Rosenberg PH. Effect of intraperitoneal bupivacaine on pain after
laparoscopic cholecystectomy. Acta Anaesthesiol Scand 1995; 39:195-8.
685. Scher KS, Scott-Conner CEH. Complication of biliary surgery. Am Surg 1987;53:16-21.
686. Schirmer BD, Dix J. Cost effectiveness of laparoscopic cholecystectomy. J Laparoendosc Surg 1992; 2:145-50.
687. Schlumpf R, Klotz HP, Wehrli H, Herzog U. A nation’s experience in laparoscopic cholecystectomy. Prospective multicenter
analysis of 3722 cases. Surg Endosc 1994; 8:35-41.
688. Schlumpf R, Klotz HP, Wehrli H, Herzog U. Laparoscopic cholecystectomy in Switzerland. Critical retrospective evaluation of
the first 3,722 cases. Swiss Professional Society of Laparoscopic and Thoracoscopic Surgery. Chirurg 1993; 64:307-13.
689. Schlup MM, Williams SM, Barbezat GO. ERCP: a review of technical competency and workload in a small unit. Gastrointest
Endosc 1997; 46:48-52.
690. Schmitz R, Rohde V, Treckmann J, Shah S. Randomized clinical trial of conventional cholecystectomy versus
minicholecystectomy. Br J Surg 1997;84:1683-6.
691. Schoenfield LJ, Lachin JM. Chenodiol (chenodeoxycholic acid) for dissolution of gallstones: the National Cooperative
Gallstone Study. Ann Int Med 1981;95:257-82.
692. Schol FP, Go PM, Gouma DJ, Kootstra G. Laparoscopic cholecystectomy in a surgical training programme. Eur J Surg 1996;
162:193-7.
192
693. Schreiber F, Steindorfer P, Pristautz H, Gurakuqi GC, Schnedl W, Trauner M. Complications and surgical interventions during
4 years of biliary extracorporeal shockwave lithotripsy. Hepatogastroen-terology 1996; 43:1124-8.
694. Schrenk P, Woisetschlager R, Wayand WU. Laparoscopic cholecystectomy. Cause of conversions in 1,300 patients and
analysis of risk factors. Surg Endosc 1995; 9:25-8.
695. Schroeder D, Baker P. Interpleural catheter for analgesia after cholecystectomy: the surgical perspective. Aust N Z J Surg
1990; 60:689-94.
696. Schweins M, Edelmann M. Ambulatory laparoscopic cholecystectomy. Chirurg 1997; 68:613-7.
697. Scott AD, Greville AC, McMillan L, Wellwood JM. Laparoscopic laser cholecystectomy: results of the technique in 210
patients. Ann R Coll Surg Engl 1992; 74:237-41.
698. Scott BB. Gastroenterology in the Trent Region in 1992 and a review of changes since 1975. Gut 1995; 36:468-72.
699. Scott EA, Black N. Appropriateness of cholecystectomy in the United Kingdom--a consensus panel approach. Gut 1991;
32:1066-70.
700. Scott EA, Black N. Appropriateness of cholecystectomy: the public and private sectors compared. Ann R Coll Surg Engl 1992;
74:97-101.
701. Scott NB, Mogensen T, Bigler D, Kehlet H. Comparison of the effects of continuous intrapleural vs epidural administration of
0.5% bupivacaine on pain, metabolic response and pulmonary function following cholecystectomy. Acta Anaesthesiol
Scand 1989; 33:535-9.
702. Scott TE, Jacoby I. Clinical decision analysis as a means of technology assessment. The effectiveness of intraoperative
cholangiography. Int J Technol Assess Health Care 1992; 8:185-97.
703. Seenu V, Misra MC. Mini-lap cholecystectomy – an attractive alternative to conventional cholecystectomy. Trop
Gastroenterol 1994; 15:29-31.
704. Sen M, Williamson RC. Acute cholecystitis: surgical management. Baillieres Clin Gastroenterol 1991; 5:817-40.
705. Sequeira R, Weinbaum F, Satterfield J, Chassin J, Mock L. Credentialing physicians for new technology: the physician’s
learning curve must not harm the patient. Am Surg 1994; 60:821-3.
706. Sharma AK, Cherry R, Fielding JW. A randomised trial of selective or routine on-table cholangio-graphy. Ann R Coll Surg Engl
1993; 75:245-8.
707. Sherman S, Lehman GA. ERCP- and endoscopic sphincterotomy-induced pancreatitis published erratum appears in
Pancreas 1992;7(3):402. Pancreas 1991; 6:350-67.
708. Sherman S, Ruffolo TA, Hawes RH, Lehman GA. Complications of endoscopic sphincterotomy. A prospective series with
emphasis on the increased risk associated with sphincter of Oddi dysfunction and nondilated bile ducts. Gastroenterology
1991; 101:1068-75.
709. Shiffman ML, Kaplan GD, Brinkman Kaplan V, Vickers FF. Prophylaxis against gallstone formation with ursodeoxycholic acid
in patients participating in a very-low-calorie diet program. Ann Intern Med 1995; 122:899-905.
710. Siegel JH, Ben Zvi JS, Pullano WE. Mechanical lithotripsy of common duct stones. Gastrointest Endosc 1990; 36:351-6.
711. Sigman HH, Fried GM, Hinchey EJ, et al. Role of the teaching hospital in the development of a laparoscopic
cholecystectomy program [see comments]. Can J Surg 1992; 35:49-54.
712. Sim RR, Nowicky DJ, McAlhany JC, Jr., Blouin GS, Blackhurst DW. Laparoscopic cholecystectomy in a community hospital
setting. Surg Gynecol Obstet 1992; 175:161-6.
713. Singh V, Kumar P, Rai HS, Singh K. Postcholecystectomy problems and the role of endoscopic retrograde
cholangiopancreatography. Br J Clin Pract 1996; 50:183-6.
714. Singson DC, Balan A. Laparoscopic cholecystectomy: the Medical Center of Delaware experience. Del Med J 1992; 64:
497-504.
715. Sitzmann JV, Pitt HA, Steinborn PA, Pasha ZR, Sanders RC. Cholecystokinin prevents parenteral nutrition induced biliary
sludge in humans. Surg Gynecol Obstet 1990; 170:25-31.
193
716. Slim K, Pezet D, Stencl J, Jr., et al. Laparoscopic cholecystectomy: an original three-trocar technique. World J Surg 1995;
19:394-7.
717. Smith EB. Complications of laparoscopic cholecystectomy. J Natl Med Assoc 1992; 84:880-2.
718. Smith JF, Boysen D, Tschirhart J, Williams T. Risks and benefits of laparoscopic cholecystectomy in the community hospital
setting. J Laparoendosc Surg 1991; 1:325-32.
719. Soehendra N, Schulz H, Nam VC, et al. ESWL and gallstone dissolution with MTBE via a naso-vesicular catheter. Endoscopy
1990; 22:176-9.
720. Solomon DH, Brook RH, Fink A. Indications for selected medical and surgical procedures – a litterature review and ratings of
appropriateness: Cholecystectomy. R-3204/3- CWF/HF/PMT/RWJ. Santa Monica: The Rand Corporation, 1986.
721. Sondenaa K, Nesvik I, Solhaug JH, Soreide O. Randomization to surgery or observation in patients with symptomatic
gallbladder stone disease. The problem of evidence-based medicine in clinical practice. Scand J Gastroenterol 1997;
32:611-6.
722. Sonnenberg A, Derfus GA, Soergel KH. Lithotripsy versus cholecystectomy for management of gallstones. A decision
analysis by Markov process. Dig Dis Sci 1991; 36:949-56.
723. Soper NJ, Dunnegan DL. Routine versus selective intra-operative cholangiography during laparoscopic cholecystectomy
[see comments]. World J Surg 1992; 16:1133-40.
724. Soper NJ, Stockmann PT, Dunnegan DL, Ashley SW. Laparoscopic cholecystectomy. The new ’gold standard’? Arch Surg
1992; 127:917-21.
725. Sorenson MK, Fancher S, Lang NP, Eidt JF, Broadwater JR. Abnormal gallbladder nuclear ejection fraction predicts success of
cholecystectomy in patients with biliary dyskinesia. Am J Surg 1993; 166:672-4.
726. Sostre S, Kalloo AN, Spiegler EJ, Camargo EE, Wagner HN, Jr. A noninvasive test of sphincter of Oddi dysfunction in
postcholecystectomy patients: the scintigraphic score [see comments]. J Nucl Med 1992; 33:1216-22.
727. Soto JA, Barish MA, Ferrucci JT. Magnetic resonance imaging of the bile ducts. Semin Roentgenol 1997; 32:188-201.
728. Spaw AT, Reddick EJ, Olsen DO. Laparoscopic laser cholecystectomy: analysis of 500 procedures. Surg Laparosc Endosc 1991;
1:2-7.
729. Spencer JA. Laparoscopic cholecystectomy letter. Can J Surg 1992; 35:346-7.
730. Spiro HM. Diagnostic laparoscopic cholecystectomy. Lancet 1992; 339:167-8.
731. Spuy S van der. Endoscopic sphincterotomy in the management of gallstone pancreatitis. Endoscopy 1981;13:25-6.
732. Stabenow Lohbauer U, Bozkurt T, Langer M, Lux G. Lysis of gallstones with methyl tert-butyl ether: percutaneous
transhepatic or transpapillary?. Dtsch Med Wochenschr 1991; 116:1537-42.
733. Stage JG, Hjortso NC, Dahl JB, Damgaard B, Hansen B, Kehlet H. Minicholecystectomy. Ugeskr Laeger 1991; 153:3228-31.
734. Stage JG, Rasmussen SG, Damgaard B, Kehlet H. Percutaneous cholecystolithotripsy. Ugeskr Laeger 1991; 153:3231-3.
735. Stage JG, Rasmussen SG, Hojgaard L, Kehlet H. Percutaneous cholecystectomy in acute cholecystitis. Ugeskr Laeger 1993;
155:3477-80.
736. Stahlschmidt M, Lotz GW, Moergel K, Maurer T. Results of conventional and laparoscopic cholecystectomy. Z Gastroenterol
1992; 30:713-6.
737. Stain SC, Cohen H, Tsuishoysha M, Donovan AJ. Choledocholithiasis. Endoscopic sphincterotomy or common bile duct
exploration [see comments]. Ann Surg 1991; 213:627-33.
738. Staritz M, Grosse A, Alkier R, Krzoska B, Meyer zum Buschenfelde KH. Therapy of choledocholithia-sis using extracorporeal
shock wave lithotripsy and adjuvant surgical endoscopy. Z Gastroenterol 1992; 30:156-61.
739. Steel RJC. The influence of surgeon case volume on outcome in site-specific cancer surgery. Eur J Surg Onc 1996;22:211-3.
740. Steele RJ, Marshall K, Lang M, Doran J. Introduction of laparoscopic cholecystectomy in a large teaching hospital: independent audit of the first 3 years. Br J Surg 1995; 82:968-71.
194
741. Steenbergen W van, Pelemans W, Fevery J. Endoscopic biliary endoprosthesis in elderly patients with large bile duct stones:
Long-term follow-up. JAGS 1992;40:57-60.
742.
Stefanini P, Carboni M, Patrassi N, Loriga P, De Bernardinis G, Negro P. Factors influencing the long term results of
cholecystectomy. Surg Gyn Obst 1974;139:734-8.
743. Steger AC, Moore KM, Hira N. Contact laser or conventional cholecystectomy: A controlled trial. Br J Surg 1988;75:223-5.
744. Steinbrook RA, Freiberger D, Gosnell JL, Brooks DC. Prophylactic antiemetics for laparoscopic cholecystectomy: ondansetron
versus droperidol plus metoclopramide. Anesth Analg 1996; 83:1081-3.
745. Steiner CA, Bass EB, Talamini MA, Pitt HA, Steinberg EP. Surgical rates and operative mortality for open and laparoscopic
cholecystectomy in Maryland [see comments]. N Engl J Med 1994; 330:403-8.
746. Steinle EW, VanderMolen RL, Silbergleit A, Cohen MM. Impact of laparoscopic cholecystectomy on indications for surgical
treatment of gallstones. Surg Endosc 1997; 11:933-5.
747. Stephenson BM, Callander C, Sage M, Vellacott KD. Feasibility of ’day case’ laparoscopic cholecystectomy. Ann R Coll Surg
Engl 1993; 75:249-51.
748. Stiegmann GV, Goff JS, Mansour A, Pearlman N, Reveille RM, Norton L. Precholecystectomy endoscopic cholangiography
and stone removal is not superior to cholecystectomy, cholangiography, and common duct exploration. Am J Surg 1992;
163:227-30.
749. Stiff G, Rhodes M, Kelly A, Telford K, Armstrong CP, Rees BI. Long-term pain: Less common after laparoscopic than open
cholecystectomy. Br J Surg 1994;81:1368-70.
750. Stirnemann H, Aebersold P, Bader M, Biaggi J, Büchler U, Nussberger P, Wyler A. Was bestimmt die prognose nach
Cholezystektomie: Anamnese, Operationsbefunde, postoperative Komplikationen? Schweiz med Wschr 1983;113:448-53.
751. Stock SE, Carlson GL, Lavelle MI, Lendrum R, Venables CW. Treatment of common bile duct stones using mono-octanoin.
Br J Surg 1992; 79:653-4.
752. Stoker ME, Vose J, O’Mara P, Maini BS. Laparoscopic cholecystectomy. A clinical and financial analysis of 280 operations.
Arch Surg 1992;127: 589-95.
753. Stokes KR, Clouse ME. Biliary duct stones: percutaneous transhepatic removal. Cardiovasc Intervent Radiol 1990; 13:240-4.
754. Stolzel U, Koszka C, Wolfer B, Kleine U, Pommerien W, Riecken EO. Relief of heterogeneous symptoms after successful gall
bladder stone lithotripsy and complete stone disappearance. Gut 1994; 35:819-21.
755. Stone HH, Fabian TC, Dunlop WE. Gallstone pancreatitis. Biliary tract pathology in relation to time of operation. Ann Surg
1981;194:305-12.
756. Strasberg SM, Hertl M, Soper NJ. An analysis of the problem of biliary injury during laparoscopic cholecystectomy
[see comments]. J Am Coll Surg 1995; 180:101-25.
757. Stromskag KE, Minor BG, Lindeberg A. Comparison of 40 milliliters of 0.25% intrapleural bupivacaine with epinephrine with
20 milliliters of 0.5% intrapleural bupivacaine with epinephrine after cholecystec-tomy. Anesth Analg 1991; 73:
397-400.
758. Suarez CA, Blandford JM, Suarez EM, Ocariz Monzon HB, Suarez DL. Limited incision cholecystecto-my. J Fla Med Assoc
1992; 79:459-63.
759. Suc B, Fontes Dislaire I, Fourtanier G, Escat J. 3606 cholecystectomies under celioscopy. The Register of the French Society of
Digestive Surgery. Ann Chir 1992; 46:219-26.
760. Sugerman HJ, Brewer WH, Shiffman ML, et al. A multicenter, placebo-controlled, randomized, double-blind, prospective
trial of prophylactic ursodiol for the prevention of gallstone formation following gastric-bypass-induced rapid weight loss.
Am J Surg 1995; 169:91-6.
761. Suits GS, Wills JT, Long III JM. More evidence for selective use of intraoperative cholangiography. J South Car Med Ass
1987;83:477-80.
195
762. Szem JW, Hydo L, Barie PS. A double-blinded evaluation of intraperitoneal bupivacaine vs saline for the reduction of
postoperative pain and nausea after laparoscopic cholecystectomy. Surg Endosc 1996; 10:44-8.
763. Tanaka M, Ikeda S, Yoshimoto H, Matsumoto S. The long-term fate of gallbladder after endoscopic sphincterotomy.
Complete follow-up study of 122 patients. Am J Surg 1987;154:505-9.
764. Targarona EM, Ayuso RM, Bordas JM, et al. Randomised trial of endoscopic sphincterotomy with gallbladder left in situ
versus open surgery for common bileduct calculi in high-risk patients [see comments]. Lancet 1996; 347:926-9.
765. Targarona EM, Balagué C, Cifuentes A, Martínez J, Trías M. The spilled stone. A potential danger after laparoscopic
cholecystectomy. Surg Endosc 1995;9:768-73.
766. Tate JJ, Lau WY, Leung KL, Li AK. Laparoscopic versus mini-incision cholecystectomy letter; comment. Lancet 1993;
341:1214-5.
767. Taylor E, Gaw F, Kennedy C. Outpatient laparoscopic cholecystectomy feasibility. J Laparoendosc Surg 1996; 6:73-7.
768. Taylor OM, Sedman PC, Jones BM, Royston CM, Arulampalam T, Wellwood J. Laparoscopic cholecystectomy without operative cholangiogram: 2038 cases over a 5-year period in two district general hospitals. Ann R Coll Surg Engl 1997; 79:376-80.
769. Taylor TV, Armstrong CP, Rimmer S, Lucas SB, Jeacock J, Gunn AA. Prediction of choledocholithiasis using a pocket
microcomputer. Br J Surg 1988;75:138-40.
770. Teilum D. Prevalence of gallstones at autopsy at the Institutes of Forensic Medicine in Aarhus and Copenhagen, Denmark,
in 1944-1985. Scand J Gastroenterol 1990; 25:401-4.
771. Teilum D, Olsen B. The prevalence of gallstones in autopsies from a Danish urban area. Frederiks-berg, 1959-85. Scand J
Gastroenterol 1988;23:813-6.
772. Teilum D, Olsen B. Cholecystectomy rate in autopsies from a Danish urban area. Frederiksberg 1914-1987. Acta Chir Scand
1989; 155:273-5.
773. Teplick SK, Brandon JC, Wolferth CC, Amron G, Gambescia R, Zitomer N. Percutaneous interventional gallbladder procedures:
personal experience and literature review. Gastrointest Radiol 1990; 15:133-6.
774. Thanh LN, Houry S, Huguier M. Cholécystectomie par laparoscopie. Complications vasculaires et biliaires. Ann Chir
1997;51:237-42.
775. Thijs C, Knipschild P, Leffers P. Does alcohol protect against the formation of gallstones? A demonstration of protopathic bias.
J Clin Epidemiol 1991; 44:941-6.
776. Thistle JL, Cleary PA, Lachin JM, Tyor MP, Hersh T. The natural history of cholelithiasis: The natioanl cooperative gallstone
study. Ann Int Med 1984;101:171-5
777. Thistle JL. Direct contact dissolution of gallstones. Sem Liv Dis 1987;7:311-6.
778. Thistle JL, May GR, Bender CE, et al. Dissolution of cholesterol gallbladder stones by methyl tert-butyl ether administered by
percutaneous transhepatic catheter. N Engl J Med 1989; 320:633-9.
779. Thorn SE, Wattwil M, Naslund I. Postoperative epidural morphine, but not epidural bupivacaine, delays gastric emptying on
the first day after cholecystectomy. Reg Anesth 1992; 17:91-4.
780. Thornell E, Jahnsson R, Svanvik J. Indomethacin reduces raised intraluminal gallbladder pressure in acute cholecystitis.
Acta Chir Scand 1985;151:261-5.
781. Thornell E, Nilsson B, Jansson R, Svanvik J. Effect of short-term indomethacin treatment on the clinical course of acute
obstructive cholecystitis. Eur J Surg 1991; 157:127-30.
782. Thune A, Appelgren L, Haglind E. Prevention of postoperative nausea and vomiting after laparoscopic cholecystectomy.
A prospective randomized study of metoclopramide and transdermal hyoscine. Eur J Surg 1995; 161:265-8.
783. Toth C. Percutaneous cholecysto-lithotripsy. Acta Chir Hung 1991; 32:69-75.
784. Trautwein EA. Dietetic influences on the formation and prevention of cholesterol gallstones. Z Ernahrungswiss 1994;
33:2-15.
196
785. Treen DC, Jr., Downes TW, 3d, Hayes DH, McKinnon WM. Outpatient cholecystectomy simulated in an inpatient population.
Am Surg 1991; 57:39-45.
786. Tritapepe R, Piro D. Mono-octanoin and methyl tert-butyl ether mixture for bile duct stones. Panminerva Med 1993;
35:22-7.
787. Troidl H, Spangenberger W, Langen R, et al. Laparoscopic cholecystectomy: technical performance, safety and patient’s
benefit. Endoscopy 1992; 24:252-61.
788. Troidl H, Spangenberger W, Dietrich A, Neugebauer E. Laparoscopic cholecystectomy. Initial experiences and results in 300
operations: a prospective follow-up study. Chirurg 1991; 62:257-65.
789. Trondsen E, Reiertsen O, Andersen OK, Kjaersgaard P. Laparoscopic and open cholecystectomy. A prospective, randomized
study. Eur J Surg 1993; 159:217-21.
790.
Trondsen E, Ruud TE, Nilsen BH, et al. Complications during the introduction of laparoscopic cholecystectomy in Norway.
A prospective multicentre study in seven hospitals. Eur J Surg 1994; 160:145-51.
791. Truensdell ED. The frequency and future of gallstones believed to be quiescent or symptomless. Ann Surg 1944;119:232-45.
792. Tsimoyiannis EC, Antoniou NC, Tsaboulas C, Papanikolaou N. Cholelithiasis during pregnancy and lactation. Prospective
study. Eur J Surg 1994; 160:627-31.
793. Tyagi NS, Meredith MC, Lumb JC, et al. A new minimally invasive technique for cholecystectomy. Subxiphoid “minimal
stress triangle”: microceliotomy [see comments]. Ann Surg 1994; 220:617-25.
794. Uchiyama K, Tanimura H, Ishimoto K, Murakami K, Nakai T, Yamazaki S. Extracorporeal shock wave lithotripsy (ESWL) for
biliary stones: a nationwide survey in Japan. Nippon Geka Hokan 1994; 63:199-207.
795. Ulrich RS. View through a window may influence recovery from surgery. Science 1984;224:420-1.
796. Unger SW, Nguyen N, Edelman DS, Unger HM. Laparoscopic approach to acute cholecystitis: a four year retrospective
review. Int Surg 1994; 79:209-12.
797. Ure BM, Troidl H, Spangenberger W, et al. Long-term results after laparoscopic cholecystectomy. Br J Surg 1995; 82:267-70.
798. Ure BM, Troidl H, Spangenberger W, et al. Preincisional local anesthesia with bupivacaine and pain after laparoscopic cholecystectomy. A double-blind randomized clinical trial. Surg Endosc 1993; 7:482-8.
799. VadeBoncouer TR, Riegler FX, Gautt RS, Weinberg GL. A randomized, double-blind comparison of the effects of interpleural
bupivacaine and saline on morphine requirements and pulmonary function after cholecystectomy. Anesthesiology 1989;
71:339-43.
800. Vaira D, D’Anna L, Ainley C, et al. Endoscopic sphincterotomy in 1000 consecutive patients [see comments]. Lancet 1989;
2:431-4.
801. Valberg LS, Jabbari M, Kerr JW, Curtis AC, Ramchaud S, Prentice RSA. Biliary pain in young women in the absence of
gallstones. Gastroenterology 1970;60:1020-6.
802. Valdivieso V, Covarrubias C, Siegel F, Cruz F. Pregnancy and cholelithiasis: pathogenesis and natural course of gallstones
diagnosed in early puerperium [see comments]. Hepatology 1993; 17:1-4.
803. Vanek VW, Bourguet CC. The cost of laparoscopic versus open cholecystectomy in a community hospital. Surg Endosc 1995;
9:314-23.
804. vanSonnenberg E, D’Agostino HB, Goodacre BW, Sanchez RB, Casola G. Percutaneous gallbladder puncture and cholecystostomy: results, complications, and caveats for safety. Radiology 1992; 183:167-70.
805. Vayda E, Mindell WR, Mueller CB. Use of hypothetical cases to investigate indications for surgery. Can J Surg 1981;24:19-21.
806. Villanova N, Bazzoli F, Taroni F, et al. Gallstone recurrence after successful oral bile acid treatment. A 12-year follow-up study
and evaluation of long-term postdissolution treatment [see comments]. Gastroenterology 1989; 97:726-31.
807. Vincent Hamelin E, Pallares AC, Felipe JA, et al. National survey on laparoscopic cholecystectomy in Spain. Results of a multiinstitutional study conducted by the Committee for Endoscopic Surgery (Associacion Espanola de Cirujanos). Surg Endosc
1994; 8:770-6.
197
808. Visset J, Hamy A, Likholatnikov D, Lerat F, Jurczak F, Paineau J. Echo-guided percutaneous cholecystostomy in the treatment
of acute cholecystitis. Apropos of 41 cases. Chirurgie 1994; 120:61-5.
809. Vogal J, Orth K, Buchler M, Beger HG. Surgical therapy of acute cholecystitis--advantages of early operation.
Z Gastroenterol 1992; 30:463-8.
810. Voitk AJ. Establishing outpatient cholecystectomy as a hospital routine [see comments]. Can J Surg 1997; 40:284-8.
811. Voitk AJ. Routine outpatient laparoscopic cholecystectomy [see comments]. Can J Surg 1995; 38:262-5.
812. Voyles CR, Petro AB, Meena AL, Haick AJ, Koury AM. A practical approach to laparoscopic cholecystectomy. Am J Surg 1991;
161:365-70.
813. Waldmeier V, Shope B. Open cholecystectomy: a same-day surgical experience. Todays OR Nurse 1992; 14:23-8.
814. Walker JW. The removal of gallstones by ether solution. Lancet 1891;1:874-5.
815. Warren BL, Marais AW. Elective cholecystectomy via a 5 cm subcostal incision. S Afr Med J 1992; 82:349-50.
816. Warwick DJ, Thompson MH. Six hundred patients with gallstones. Ann R Coll Surg Engl 1992; 74:218-21.
817. Wastell C. Laparoscopic cholecystectomy. Better for patients and health service. BMJ 1991;302:303-4.
818. Watkins JL, Etzkorn KP, Wiley TE, DeGuzman L, Harig JM. Assessment of technical competence during ERCP training.
Gastrointest Endosc 1996; 44:411-5.
819. Watson A, Better N, Kalff V, Nottle P, Scelwyn M, Kelly MJ. Cholecystokinin (CCK)-HIDA scintigraphy in patients with
suspected gall-bladder dysfunction [see comments]. Australas Radiol 1994; 38:30-3.
820. Watson RGP, Love AHG. Intragastric bile acid concentrations are unrelated to symptoms of flatulent dyspepsia in patients
with and without gallbladder disease and postcholecystectomy. Gut 1987;28:131-6.
821. Wayand W, Rieger R, Woisetschlager W. Laparoscopic surgery--the revolution in gallstone treatment. Acta Med Austriaca
1992; 19:41-4.
822. Wayand WU, Gitter T, Woisetschlager R. Laparoscopic cholecystectomy: the Austrian experience. J R Coll Surg Edinb 1993;
38:152-3.
823. Weber A, Muñoz J, Garteiz D, Cueto J. Use of subdiaphragmatic bupivacaine installation to control postoperative pain after
laparoscopic surgery. Surg Lap Endosc 1997;7:6-8.
824. Wegge C, Kjærgaard J. Evaluation of symptoms and signs of gallstone disease in patients admitted with upper abdominal
pain. Scand J Gastroenterol 1985;20:933-6.
825. Wehrmann T, Marek S, Hanisch E, Lembcke B, Caspary WF. Causes and management of recurrent biliary pain after successful
nonoperative gallstone treatment. Am J Gastroenterol 1997; 92:132-8.
826. Wehrmann T, Wiemer K, Lembcke B, Caspary WF, Jung M. Do patients with sphincter of Oddi dysfunction benefit from
endoscopic sphincterotomy? A 5-year prospective trial. Eur J Gastroenterol Hepatol 1996; 8:251-6.
827. Weinsier RL, Wilson LJ, Lee J. Medically safe rate of weight loss for the treatment of obesity: a guideline based on risk of
gallstone formation. Am J Med 1995; 98:115-7.
828. Weinstein MC, Coley CM, Richter JM. Medical management of gallstones: a cost-effectiveness analysis. J Gen Intern Med
1990; 5:277-84.
829. Weitemeyer R. The treatment of ampullary stenosis by endoscopic sphincterotomy (EST). Am J Surg 1994; 167:493-6.
830. Welbourn CR, Beckly DE, Eyre Brook IA. Endoscopic sphincterotomy without cholecystectomy for gall stone pancreatitis.
Gut 1995; 37:119-20.
831. Wenckert A, Robertson B. The natural course of gallstone disease. Eleven-year review of 781 nonoperated cases.
Gastroenterology 1966;50:376-81.
832. Wendtland Born A, Wiewrodt B, Bender SW, Weitzel D. Prevalence of gallstones in the neonatal period. Ultraschall Med
1997; 18:80-3.
198
833. Wenk H, Thomas S, Schmeller N, Lange V, Schildberg FW. Percutaneous transhepatic cholecysto-lithotripsy (PTCL).
Endoscopy 1989; 21:221-2.
834. Wennberg J, Gittelsohn A. Small area variations in health care delivery. Science 1973;182:1102-8.
835. Wenner J, Graffner H, Lindell G. Laparoscopic cholecystectomy. Cost-effective gallstone surgery Laparoskopisk
kolecystektomi. Kostnadseffektiv gallstenskirurgi. Lakartidningen 1995; 92:763-5.
836. Westlake PJ, Hershfield NB, Kelly JK, et al. Chronic right upper quadrant pain without gallstones: does HIDA scan predict
outcome after cholecystectomy? Am J Gastroenterol 1990; 85:986-90.
837. Wherry DC, Marohn MR, Malanoski MP, Hetz SP, Rich NM. An external audit of laparoscopic cholecystectomy in the steady
state performed in medical treatment facilities of the Department of Defense. Ann Surg 1996; 224:145-54.
838. Wherry DC, Rob CG, Marohn MR, Rich NM. An external audit of laparoscopic cholecystectomy performed in medical
treatment facilities of the department of Defense. Ann Surg 1994; 220:626-34.
839. Wieden TE, Gerberding J, Weiser HF. Laparoscopic cholecystectomy--benefit or risk?. Leber Magen Darm 1992; 22:22-6.
840. Wilbur RS, Bolt RJ. Incidence of gall bladder disease in “normal” men. Gastroenterology 1959;36:251-5.
841. Williams HJ, Bender CE, leRoy AJ. Dissolution of cholesterol gallstones using Methyl Tert-Butyl Ether. Cardiovasc Intervent
Radiol 1990;13:272-7.
842. Willekes CL, Widmann WD. Empyema from lost gallstones: a thoracic complication of laparoscopic cholecystectomy.
J Laparoendosc Surg 1996; 6:123-6.
843. Wilson MS, Tweedle DE, Martin DF. Common bile duct diameter and complications of endoscopic sphincterotomy. Br J Surg
1992; 79:1346-7.
844. Wilson P, Jamieson JR, Hinder RA, et al. Pathologic duodenogastric reflux associated with persistence of symptoms after
cholecystecto my. Surgery 1995; 117:421-8.
845. Wilson PG, Ogunbiyi O, Neoptolemos JP. The timing of endoscopic sphincterotomy in gallstone acute pancreatitis. Eur J
Gastroenterol Hepatol 1997; 9:137-44.
846. Wilson RG, Macintyre IM. Symptomatic outcome after laparoscopic cholecystectomy [see comments]. Br J Surg 1993;
80:439-41.
847. Wilson YG, Rhodes M, Ahmed R, Daugherty M, Cawthorn SJ, Armstrong CP. Intramuscular diclofenac sodium for
postoperative analgesia after laparoscopic cholecystectomy: a randomised, controlled trial. Surg Laparosc Endosc 1994;
4:340-4.
848. Windsor JA, Vokes DE. Early laparoscopic biliary injury: experience in New Zealand. Br J Surg 1994; 81:1208-11.
849. Windsor JA, Vokes DE. Early experience with minimally invasive surgery: a New Zealand audit. Aust N Z J Surg 1994; 64:81-7.
850. Winkler E, Kaplan O, Gutman M, Skornick Y, Rozin RR. Role of cholecystostomy in the management of critically ill patients
suffering from acute cholecystitis [see comments]. Br J Surg 1989; 76:693-5.
851. Wojtun S, Gil J, Gietka W, Gil M. Endoscopic sphincterotomy for choledocholithiasis: a prospective single-center study on the
short-term and long-term treatment results in 483 patients. Endoscopy 1997; 29:258-65.
852. Wolfe BM, Gardiner BN, Leary BF, Frey CF. Endoscopic cholecystectomy. An analysis of complications. Arch Surg 1991;
126:1192-6.
853. Wollesen JM. Efterundersøgelse af 193 medicinsk behandlede galdestenspatienter. Ugeskr Læg 1945;107:149-53.
854. Wolpers C. Veränderungen an “stillen” gallenblasensteinen. DMW 1986;111:1186-91.
855. Yamashita Y, Kurohiji T, Kakegawa T. Evaluation of two training programs for laparoscopic cholecystectomy: incidence of
major complications. World J Surg 1994; 18:279-85.
856. Yap L, Wycherley AG, Morphett AD, Toouli J. Acalculous biliary pain: cholecystectomy alleviates symptoms in patients with
abnormal cholescintigraphy [see comments]. Gastroenterology 1991; 101:786-93.
857. Yip A, Lam KH. An evaluation of routine operative cholangiography. Aust N Z J Surg 1988;58:391-5
199
858.
Yoshida T, Kobayashi E, Suminaga Y, et al. Hormone-cytokine response. Pneumoperitoneum vs abdominal wall-lifting in
laparoscopic cholecystectomy. Surg Endosc 1997; 11:907-10.
859. Yuan C-Y, Yuan C-C, Yuan T-K, Wei T-C, Obata H, Hanyu F, Takasaki K, Kobayashi S. Epidemiologi-cal survey of biliary
disease in southern Taiwan – an ultrasonic study of 3004 asymptomatic subject from a general population. J Tokyo Wom
Med Coll 1987;57:807-12.
860. Zech ER, Simmons LB, Kendrick RR, Soballe PW, Olcese JAM, Goff II WB, Lawrence DP, deWeese RA. Cholecystokinin
enhanced hepatobiliary scanning with ejection fraction calculation as an indicator of disease of the gallbladder. Surg Gyn
Obst 1991;172:21-4.
861. Zhao Y, Zhang R, Hu Y, Li R, Liang L, Gang Y. An epidemiological survey of gallstones with gray-scale ultrasound. Hua Hsi I
Ko Ta Hsueh Hsueh Pao 1990; 21:217-20.
862. Zisman A, Gold Deutch R, Zisman E, et al. Is male gender a risk factor for conversion of laparoscopic into open
cholecystectomy? Surg Endosc 1996; 10:892-4.
863. Zoubek V. Incidence of cholecystolithiasis in a population 20-59 years of age. Cas Lek Cesk 1992; 131:268-70.
864. Äärimaa M, Mäkelä P. The cystic duct stump and the postcholecystectomy syndrome. Ann Chir Gynaecol 1981;70:297-303.
865. Schwesinger WH, Page CP, Sirinek KR, Levine BA, Aust B. Biliary pancreatits. Operative outcome with a selective approach.
Arch Surg 1991;126:836-40.
866. de Waele B, Peterson T, Smekens L, Willems G. Common bile duct stones in acute biliary pancreatits: An endoscopic study.
Surg Lap Endoscop 1997;7:248-50.
867. Sohi HS, Heipel J, Inman KJ, Chinnick B, Cunningham DG, Holliday RL, Girotti MJ. Preoperative transdermal scopolamine
does not reduce the level of nausea and frequency of vomiting after laparoscopic cholecystectomy. CJS 1994;37:307-18.
868. Orth K, Haas S, Oettinger W, Beger HG. Da risiko der elektiven Cholezystectomie. Z Gastroenterol 1990;28:616-20.
869. Reddick EJ, Olsen DO. Laparoscopic laser cholecystectomy. Surg Endosc 1989;3:131-133.
870. O’Dwyer PJ, Murphy JJ, O’Higgins NJ. Cholecystectomy through a 5 cm subcostal incision. Br J Surg 1990;77:1189-90.
871. Kumar N, Annudath KB, Shukla HS, Singh A, Kumar K. Postoperative intravenous drip infusion is not required after
minilaparotomy cholecystectomy. HPB Surgery 1997;10:279-81.
200
Appendix 2.
The National Hospital
Discharge Register
E XTRACT FROM THE N ATIONAL H OSPITAL D ISCHARGE R EGISTER
Data from the National Hospital Discharge Register was used to acquire a
general view of developments in the treatment of biliary tract disorders in
Denmark. All the hospital admissions in the period 1978-95 that included
one or more codes for treatment of the biliary tracts were studied and the
following information extracted: admission date, discharge date, discharge
diagnoses, treatments, method of admission (acute, elective), name of hospital, name of department, age, gender and municipality of residence. The
treatments were classified according to the National Health Board's classification of operations and treatments (1st version in the period 1978-80;
2nd version in the period 1981-88; and 3rd version in the period 1989-95.
Note: the codes are national and will hardly be comparable with other national codes), and the diagnoses were classified according to the international classification of diseases (ICD-8 in the period 1978-93 and ICD-10
in the period 1994-95). ICD-9 was never introduced in Denmark.
Basic material (figure 1) was collated. It includes all hospital admissions containing treatment codes or codes for diagnostic invasive examinations that can be related to biliary tracts. Excluded were diagnosis codes for malign liver, pancreas and biliary tract conditions.
FIGURE 1
The basic material
Treatment codes or codes for diagnostic invasive procedures related to biliary tracts:
1978-80:
4732-4814; 4829; 9105
1981-88:
4732-4829;9105
1989-95:
47320-48291;91050,91059
Excluding diagnosis codes for malign liver, pancreas or biliary tract conditions:
1978-93:
155.00 – 157.99; 197.79; 197.89; 230.50 – 230.69
1994-95:
C22.0 – C25.9; C78.7; D01.5; D37.6
A total of 111,769 admissions were identified, 11,397 of them with one of
the malign diagnosis codes mentioned in figure 1. These diagnosis groups
201
were excluded because the main object of the treatment received by the
vast majority of these patients was the aforementioned malign conditions, not gallstones.
A further 475 cases were excluded because the patients were from the
Faeroe Islands, Greenland or abroad, and 94 were excluded because of
obvious mistakes in the register. These consist mainly of patients admitted
to medical or anaesthesiology departments after a stay in a surgical department and who were accorded the same treatment code on both occasions,
or of re-admissions to surgical departments for repeat cholecystectomies.
This left a total of 99,803 hospital admissions covering 87,007 patients.
Classification of hospital admissions
Based on the treatment codes, it was possible to place each admission in
one of the categories listed below. When defining categories, the treatment
codes are stated for each of the three sub-periods. In many cases, they are
almost identical, but as a rule the number of treatment codes has increased over the years. Overall, they can be divided into diagnostic ERCP and
invasive procedures (figure 2), with diagnostic ERCP including treatment
codes 9105 and 91050-91059 with a total of 17,548 admissions, and the
invasive procedures covering the remaining 82,255 admissions.
FIGURE 2
All invasive procedures
1978-80:
4732-4814; 4829
1981-88:
4732-4829
1989-95:
47320-48291
The invasive procedures can be divided into a number of typical treatments (figures 3-14).
FIGURE 3
Simple cholecystectomy
Hospital stays during which the patient had a gallbladder removed without simultaneous choledochal exploration or biliodigestive
anastomosis.
Treatment codes:
1978-80:
4736, 4742
1981-88:
4736, 4742
1989-95:
47360, 47365, 47420
Without simultaneous occurrence of the following treatment codes:
202
1978-80:
4756; 4758; 4760; 4764-4798; 4808-4809; 4829
1981-88:
4756; 4758; 4760; 4764-4798; 4806-4809; (4827 & 9105); 4829
1989-95:
47560; 47580; 47600; 47640-47980; 48051-48090; (48270 & 91050-9); 48271-48275; 48290-48291
FIGURE 4
Cholecystectomy with endoscopic choledochal exploration
Hospital stays during which the patient had the gallbladder removed and during which an endoscopic procedure was performed on
the bile duct. Open sphincterotomy or biliodigestive anastomosis were not performed.
Treatment codes:
1978-80:
4736
1981-88:
4736
1989-95:
47360 og 47365
as well as at least one of following treatment codes
1978-80:
(4786 & 9105); 4787
1981-88:
(4786 & 9105); 4787; 4809; (4827 & 9105)
1989-95:
47702; 47711; (47860 & 91050); 47870; 47961; (48270 & 91050-9); 48051; 48052; 48090; 48095; 48271; 48291
Without simultaneous occurrence of the following treatment codes:
1978-80:
4776, 4794, 4796, 4798
1981-88:
4776, 4785, 4791, 4794, 4796, 4798
1989-95:
47760, 47801, 47850, 47910, 47940, 47960, 47980
FIGURE 5
Cholecystectomy with open choledochal exploration
Hospital stay during which the patient had the gallbladder removed and had an open operation performed on the bile duct during
the same stay. Open sphincterotomy or biliodigestive anastomosis were not performed.
Treatment codes:
1978-80:
4736
1981-88:
4736
1989-95:
47360 og 47365
as well as at least one of the following treatment codes:
1978-80:
4764, 4766, 4768, 4769, 4774, 4778, 4780, 4790, 4792, 4808
1981-88:
4764, 4766, 4768, 4769, 4774, 4778, 4780, 4790, 4792, 4808
1989-95:
47640, 47660, 47680, 47690, 47740, 47780, 47800, 47809, 47900, 47920, 48080
Without simultaneous occurrence of the following treatment codes:
1978-80:
4776, (4786 & 9105), 4794, 4796, 4798
1981-88:
4776, 4785, (4786 & 9105), 4791, 4794, 4796, 4798
1989-95:
47760, 47801, 47850, (47860 & 91050-9), 47910, 47940, 47960, 47980
203
FIGURE 6.
Cholecystectomy with open biliodigestive anastomosis
Hospital stay during which the patient had the gallbladder removed and open biliodigestive anastomosis was performed during the
same stay.
Treatment codes:
1978-80:
4736
1981-88:
4736
1989-95:
47360 og 47365
as well as at least one of the following treatment codes:
1978-80:
4776, 4794, 4796, 4798
1981-88:
4776, 4785, 4791, 4794, 4796, 4798
1989-95:
47760, 47801, 47850, 47910, 47940, 47960, 47980
No treatment codes were excluded
FIGURE 7.
Endoscopic choledochal exploration without simultaneous cholecystectomy
Hospital stay during which the patient had an endoscopic operation performed on the biliary tracts. During the same stay in hospital,
neither cholecystectomy, nor open sphincterotomy nor biliodigestive anastomosis were performed.
Treatment codes:
1978-80:
(4786 & 9105), 4787
1981-88:
(4786 & 9105), 4787, 4809, (4827 & 9105)
1989-95:
47702, 47711, (47860 & 91050-9), 47870, 47961, (48270 & 91050-9), 48051, 48052, 48090, 48095, 48271,
48291
Without simultaneous occurrence of the following treatment codes:
1978-80:
4736, 4756, 4758, 4760, 4776, 4794, 4796, 4798/
1981-88:
4736, 4756, 4758, 4760, 4776, 4785, 4791, 4794, 4796, 4798/
1989-95:
47360, 47365, 47560, 47580, 47600, 47760, 47801, 47850, 47910, 47940, 47960, 47980
FIGURE 8
Open choledochal exploration without simultaneous cholecystectomy
Hospital stay during which the patient had an open operation performed on the biliary duct. During the same stay in hospital, neither
cholecystectomy, open sphincterotomy nor bilio-digestive anastomosis were performed.
Treatment codes:
1978-80:
4764, 4766, 4768, 4774, 4778, 4780, 4790, 4792, 4808
1981-88:
4764, 4766, 4768, 4769, 4774, 4778, 4780, 4790, 4792, 4808
1989-95:
47640, 47660, 47680, 47690, 47740, 47780, 47800, 47809, 47900, 47920, 48080
Without simultaneous occurrence of the following treatment codes:
204
1978-80:
4736, 4756, 4758, 4760, 4776, (4786 & 9105), 4794, 4796, 4798
1981-88:
4736, 4756, 4758, 4760, 4776, 4785, (4786 & 9105), 4791, 4794, 4796, 4798
1989-95:
47360, 47365, 47560, 47580, 47600, 47760, 47801, 47850, (47860 & 91050-9), 47910, 47940, 47960, 47980
FIGUR 9
Open biliodigestive anastomosis without simultaneous cholecystectomy
Hospital stay during which the patient had open biliodigestive anastomosis performed without having a cholecystectomy performed
during the same stay.
Treatment codes:
1978-80:
4756, 4758, 4760, 4776, 4794, 4796, 4798
1981-88:
4756, 4758, 4760, 4776, 4785, 4791, 4794, 4796, 4798
1989-95:
47560, 47580, 47600, 47760, 47801, 47850, 47910, 47940, 47960, 47980
Without simultaneous occurrence of the following treatment codes:
1978-80:
4736
1981-88:
4736
1989-95:
47360 og 47365
FIGURE 10
Endoscopic biliodigestive anastomosis
Hospital stay during which the patient had a biliodigestive anastomosis performed endoscopically (cholecysto-gastrostomy or cholecystoduodenotomy) without simultaneous exploration of the choledochus duct or open bilidigestive anastomosis.
Treatment codes:
1989-95:
47561, 47581
Without simultaneous occurrence of the following treatment codes:
1989-95:
47360, 47365, 47420, 47560, 47580, 47600-48090; 48270-48275; 48290-48291
FIGURE 11
Endoscopic tubulation of the choledochus duct (without invasive procedures)
Hospital stay during which the patient had an endoscopic tubulation of the biliary tracts performed without other forms of invasive
operation.
Treatment codes:
1978-80:
4804
1981-88:
4804
1989-95:
48039, 48040
Without simultaneous occurrence of the following treatment codes:
1978-80:
4732 – 4803; 4806 – 4829
1981-88:
4732 – 4803; 4806 – 4829
1989-95:
47320 – 48030; 48051 – 48291
205
FIGURE 12
Exploration of the gallbladder
Hospital stay during which the patient had the gallbladder opened without stones being found. The gallbladder was not removed
and neither exploration of the choledochus nor biliodigestive anastomosis were performed.
Treatment codes:
1978-80:
4732, 4734
1981-88:
4732, 4734
1989-95:
47320, 47340
Without simultaneous occurrence of the following treatment codes:
1978-80:
4736 – 4798; 4808; 4829
1981-88:
4736 – 4798; 4806 – 4809; (4827 & 9105); 4829
1989-95:
47360-47980; 48051 – 48090; (48270 & 91050-9); 48271- 48275; 48290 – 48291
FIGURE 13
Cholecystolithotomy
Hospital stay during which the patient had stones removed from the gallbladder. The gallbladder was not removed and neither exploration of the choledochus nor biliodigestive anastomosis were performed.
Treatment codes:
1978-80:
4738
1981-88:
4738
1989-95:
47380
Without simultaneous occurrence of the following treatment codes:
1978-80:
4736; 4742 – 4798; 4808; 4829
1981-88:
4736; 4742 – 4798; 4806 – 4809; (4827 & 9105); 4829
1989-95:
47360; 47365; 47420 – 47980; 48051 – 48090; (48270 & 91050-9); 48271- 48275; 48290 – 48291
FIGURE 14
Percutaneous cholangiography (as only procedure)
Hospital stay during which the patient had percutaneous cholangiography performed without any other form of invasive treatment.
Treatment codes:
1978-80:
4803, 4810
1981-88:
4803, 4810
1989-95:
48030, 48100
Without simultaneous occurrence of the following treatment codes:
206
1978-80:
4732 – 4798; 4808; 4814 – 4829
1981-88:
4732 – 4798; 4808; 4809; 4814 – 4829
1989-95:
47320 – 47980; 48051 – 48090; 48140 – 48291
Table 1 shows the overall distribution of all admissions.
TABLE 1
99,803 admissions in the period 1978-95
%a
(N=99,803)
%a
(N=82,255)
66,9
81,2
55,021
55.1
66.9
565
0.6
0.7
9,248
9.3
11.2
335
0.3
0.4
1,597
1.6
1.9
13,0
15,7
10,160
10.1
12.4
1,130
1.1
1.4
124
0.1
0.2
1,518
1.5
1.8
17,548
17.6
1,303
1.3
1.6
Percutaneous tubulation
432
0.4
0.5
Unclassifiable or rare operations
822
0.8
1.0
Procedure
Antal
Cholecystectomy
as only procedure
with endoscopic bile duct treatment
with open bile duct treatment
with open and endoscopic bile duct treatment
with biliodigestive anastomosis
Bile duct treatment without simultaneous cholecystectomy
Endoscopic bile duct treatment or tubulation
Open bile duct treatment
Both endoscopic and open bile duct treatment
Biliodigestive anastomosis
Miscellaneous
Diagnostic ERCP
Exploration of the gallbladder and cholecystolithotomy
Total
99,803
a: In the first column, the percentage is calculated on the basis of all hospital admissions, while in the other column it is only calculated
on the basis of those stays in hospital during which invasive operations (i.e. excluding ERCP) were performed.
Multiple admissions of the same patient are counted as one course of treatment, provided less than a year elapsed between the separate admissions. During this process, the following index admissions were combined:
❖
“Cholecystectomy with both open and endoscopic choledochus treatment” has
been combined with “cholecystectomy with open bile duct treatment”
❖
“Both endoscopic and open choledochus treatment” have been placed under
“open bile duct treatment”
❖
“Cholecystolithotomy” has been combined with “exploration of the gallbladder”
❖
“Percutaneous tubulation of biliary tracts” has been combined with “miscellaneous”
C LASSIFICATION ACCORDING TO DIAGNOSIS
The basic material and the different treatment groups can be divided according to diagnosis and whether or not ERCP was performed. The diagnosis codes help identify those patients who were treated because of an
207
illness related to the biliary tracts, and whether or not stones were present in the gallbladder, in the bile ducts or there was a cholecystitis.
The diagnosis codes were changed during the survey period. ICD8
was used in 1978-1993, while ICD10 was used in 1994-1995. ICD9 was
never introduced in Denmark.
FIGURE 15
Biliary tract diagnoses
1978-93:
574.00 – 574.99; 575.00 – 575.99; 576.00 – 576.99
1994-95:
K80.0 – K83.9; K87.0
Stones in the gallbladder
1978-93:
574.00, 574.01, 574.02, 574.07, 574.08, 574.09
1994-95:
K80.0 – K80.2, K80.8
Acute cholecystitis
1978-93:
574.01, 574.02, 575.00, 575.02, 575.03, 575.08, 575.09
1994-95:
K80.0, K80.4, K81.0, K81.8, K81.9
Note: K81.8 & K81.9 can represent chronic cholecystitis but have been included here in order not to overlook some cases. They constitute
only 1% of the total
Stones in the bile ducts
1978-93:
574.03, 574.04, 574.05, 574.06
1994-95:
K80.3, K80.4, K80.5
Acute cholangitis
1978-93:
574.04, 574.05, 575.04, 575.08, 575.09
1994-95:
K80.3, K80.4, K83.0
Benign tumours in liver/bile-tract/pancreas
1978-93:
211.50 – 211.69
1994-95:
D13.4; D13.5; D13.6; D13.7
Acute pancreatitis
1978-93:
577.00 – 577.09
1994-95:
K85.9
Dyskinesia/post-cholecystectomy syndrome
1978-93:
576.00
1994-95:
K83.4, K91.5
Abdominal pains
1978-93:
785.51, 785.52, 785.59
1994-95:
R10.0 – R10.8
The change from ICD8 to ICD10 meant that in 1994 and 1995 it was not
possible to differentiate with 100% certainty between stones in the gallbladder and stones in the bile ducts. In addition, problems may have ari-
208
sen with the diagnosis acute cholecystitis, as there was an appreciable rise
in the registration of acute cholecystitis in 1994 and 95 without any corresponding rise in the proportion of patients admitted as acute cases. As
a result, this report is somewhat reserved in its interpretation of results
that are dependent on diagnoses from the National Hospital Discharge
Register in the years 1994 and 1995.
V ALIDATION OF THE N ATIONAL H OSPITAL D ISCHARGE R EGISTER
In order to validate the information from the National Hospital Discharge
Register the following extracts were taken from the 90,582 treatment
courses (see section 2.1.1):
1. A random extract of approx. 10% of treatments in each of the years of discharge
1979, 1985 and 1993. A total of 1,327 courses of treatment
2. A random extract of approx. 10% of all courses of treatment only consisting of diagnostic ERCP in each of the years of discharge 1979, 1985 and 1993. A total of 229
courses of treatment.
3. All courses of treatment in the years 1978-1995 where the index treatment was
cholecystectomy with or without operation on the bile ducts, and where the original stay in hospital was followed by one or more re-admissions for other treatment of the biliary tract. The diagnosis according to the index treatment had to be
gallbladder stones (because of problems with the new diagnosis classification system all gallstone diagnoses have, however, been included for the years 1994 and
1995). A total of 539 courses of treatment.
4. A random extract of approx. 2% of all admissions for each of the years 1979, 1985
and 1993 to surgical departments in cases where a gall-stone diagnosis was made
but where no treatment code was stipulated. A total of 202 admissions.
A total of 3,570 medical comments were recalled from the respective hospitals for all admissions in the (1,327+229+539) 2,095 courses of treatment (3,368 hospital admissions) covered in points 1-3 plus the 202 covered in point 4.
The validation procedure has not yet been completed, but at the time
of writing, 71% of the medical comments have been returned and reviewed. Thus, the breakdown of the figures represents a provisional result. In this report, points 1, 2 and 4 have been used to validate the treatment codes in the National Hospital Discharge Register, while point 3
supplemented by point 1 has been used to assess the extent to which
courses of treatment involving multiple admissions are due to complica-
209
tions related to the disease or to the procedure. If the latter is the case,
classification of courses of treatment could be used as a screening instrument for monitoring complications related to procedures related to simple cholecystectomy. The results are covered in this report, section 2.1.2.
D EVELOPMENTS IN THE USE OF DIFFERENT TECHNOLOGIES FOR TREATMENT OF PATIENTS
WITH BILE DUCT DISORDERS , 1978-95
In this section, the curves show developments in a number of index treatments for bile duct diseases that are only referred to summarily in the
report.
FIGURE 16.
Cholecystectomy with open bile duct surgery – with biliary tract diagnoses
Rate per 100.000
30
25
20
15
10
5
0
Year 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95
Women
210
Men
FIGURE 17.
Cholecystectomy with endoscopic bile duct surgery – with biliary tract diagnoses
Rate per 100.000
5
4
3
2
1
0
Year 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95
Women
Men
FIGURE 18.
Cholecystectomy with biliodigestive anastomosis – with biliary tract diagnoses
Rate per 100.000
5
4
3
2
1
0
Year 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95
Women
Men
211
FIGURE 19.
Cholecystectomy with operation on the bile ducts – with biliary tract diagnoses
Rate per 100,000
30
25
20
15
10
5
0
Year 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95
Women
Men
FIGURE 20.
Open operation on the bile ducts without cholecystectomy – with biliary tract diagnoses
Rate per 100,000
6
5
4
3
2
1
0
Year 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95
Women
212
Men
FIGURE 21.
Endoscopic operation on bile ducts without cholecystectomy – with biliary tract diagnoses
Rate per 100,000
35
30
25
20
15
10
5
0
Year 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95
Women
Men
FIGURE 22.
Biliodigestive anastomosis without cholecystectomy – with biliary tract diagnoses
Rate per 100,000
5
4
3
2
1
0
Year 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95
Women
Men
213
Appendix 3
Literature
S EARCH OF LITERATURE
Index Medicus
On a previous occasion, a search was conducted of Index Medicus for the
period 1978-1990 for all keywords concerning bile, biliary tracts, gallstones and treatment thereof.
MEDLINE
A search was performed for the period January 1989 – November 1997.
Search criteria:
❖
❖
❖
explode "BILIARY-TRACT-SURGERY"/ without-subheadings, adverse-effects, classification, contraindications, economics, history, instrumentation, mortality, methods, nursing, psychology, rehabilitation, statistics-and-numerical-data, standards, trends, utiliszation - in MJME (Major Mesh).
however, without "PORTOENTEROSTOMY,-HEPATIC"/ all subheadings
explode "BILIARY-TRACT-DISEASES"/ without-subheadings, blood, blood-supply, cerebrospinal-fluid, chemistry, chemically-induced, classification, congenital,
complications, diet-therapy, diagnosis, drug-therapy, economics, ethnology, embryology, enzymology, epidemiology, etiology, genetics, history, immunology,
metabolism, microbiology, mortality, nursing, pathology, prevention-and-control, physiopathology, parasitology, psychology, radiography, rehabilitation,
radio-nuclide-imaging, radiotherapy, secondary, secretion, surgery, therapy,
ultrastructure, urine, ultrasonography, virology - in MJME (Major Mesh).
Approx. 23,000 abstracts were reviewed and a total of 7,039 were
deemed relevant to this report and transferred into a RefMan database.
EMBASE
A search was conducted for randomised surveys involving laparoscopic
cholecystectomy for the period up to and including November 1997
(Search criteria: ?olecystectomy, randomi?ed og laparoscop?).
214
Cochrane Library
A search was conducted for randomised surveys involving diagnostics,
prevention and treatment of biliary tract diseases.
Bibliographies
The bibliographies in the articles read were studied to identify additional
references.
C RITICAL EVALUATION OF THE LITERATURE
In order to avoid biased interpretations, it was necessary to define in advance the principles to be used for the literature study. There is now so
much literature about gallstone treatments that by accentuating the importance of different articles, support can be found for widely divergent
points of view regarding the treatment of the same categories of illness.
For this report, it has not been possible to conduct an in-depth study of
the literature relating to all areas since the effort involved would correspond to several years of work. This work is being done at the moment
under the auspices of the Cochrane Collaboration. The purpose of the
Cochrane Collaboration84 is to collate all randomised surveys of diagnostics, prevention, treatment and care of diseases and to review them systematically – in other words, to review articles according to fixed criteria.
One reason for the international scope of the collaboration is to make sure
that all language areas are covered. There are a number of methodological problems involved in collating the literature291.
Principles for evaluating individual articles
Randomised surveys
1. Inclusion and exclusion criteria must be well defined
2. The randomisation has to be consistent
- Specification of the duration of the study; the proportion of relevant patients
randomised; exclusion after randomisation plus drop-out rate during treatment.
- Patients must be allocated to the different interventions on the basis of the
chance principle and be blinded (computerised, closed envelopes, etc.). Quasi
randomisation (e.g. on surgeon or department) is unacceptable.
- The analyses have to be made according to the principle of ‘intention to treat’,
i.e. once a patient has been allocated to a treatment, he is included in this treatment group regardless of how his course of treatment develops.
215
- The number of patients who are excluded or who drop out after randomisation
has to be less than 10% and the drop-out rate must not be spread unequally between the groups.
3. The extent to which the treatment is blind must be stated, and this is particularly
important in surveys about pain, bed days and convalescence582.
4. The method of treatment has to be well described and the extent to which the doctors treating the patients have been trained in the procedure must also be clearly
stipulated.
The above criteria were used in the assessment of the randomised surveys
and lead to either exclusion (if points 1 and 2 were not fulfilled) or to explanation of differences in the results achieved by the different surveys
(points 3 and 4).
Clinical series
Ideally, the following criteria ought to be fulfilled:
❖
Inclusion and exclusion criteria must be well defined
❖
The series must be consecutive and the time interval stipulated
❖
The series must be of a certain size
❖
The method of treatment must be well described and the extent to which the
doctors treating the patients have been trained in the procedure must also be stipulated.
Deviations from the above mentioned criteria must be mentioned in the
text or in the relevant tables.
In which areas has the available literature been systematically studied?
❖
Follow up studies of patients with stones in the gallbladder
❖
Descriptions of gallstone symptoms
❖
Comparisons between different technologies for simple cholecystectomy
❖
Randomised surveys of different technologies for treatment of stones in the biliary
tracts
This report covered the following language areas: Danish, Norwegian,
Swedish, English, German and French. Articles pertaining to randomised
surveys in other languages have been translated into English or Danish.
216
S ELECTED LITERATURE
Randomised trials of different forms of access to cholecystectomy
Cholecystectomy by laparoscopy versus minilaparotomy
Seven randomised trials that compared laparoscopic cholecystectomy to
cholecystectomy by minilaparotomy were identified. The surveys covered
a total of 1,011 patients65, 148, 421, 483, 500, 504, 766. Four of the surveys, i.e. representing 199 (20%) of the patients, did not fulfil the randomisation requirements65, 148, 421, 766. One500 of the three remaining works only performed an analysis according to the “intention to treat” principle for data
concerning length of stay in hospital. Only one study483 was blinded and
only one work stated that the surgeons were trained in both procedures483.
Cholecystectomy by laparoscopic versus traditional open cholecystectomy
Nineteen randomised trials were identified that compare laparoscopic
cholecystectomy with traditional open cholecystectomy. They cover 959
patients12, 75, 79, 174, 190, 246, 266, 337, 350, 379, 410, 490, 522, 579, 621, 634, 654, 681, 789. The vast
majority of works in this category are quite small and are about anaesthesiology and physiological trials in which no attempt was made to explain the randomisation procedure. Sufficient randomisation procedures
were only stipulated in four works79, 337, 579, 789 covering 151 patients. Only
one study579 was blinded.
Cholecystectomy by minilaparotomy versus traditional open cholecystectomy
Four randomised trials were identified that compare cholecystectomy by
minilaparotomy with traditional open cholecystectomy. They covered 391
patients51, 574, 690, 703. One of the works covering 50 patients51 did not describe the randomisation procedure sufficiently. None of the studies were
blinded.
Randomised trials regarding pain relief and nausea/discomfort after simple cholecystectomy
Various initiatives designed to reduce postoperative pain, nausea and
other forms of discomfort have been analysed in several randomised trials. Within the time framework of this report, it has not been possible to
study them all systematically. The references are stated here for use in any
follow-up work on reference programmes about gallstone treatment.
217
The location of the incision
Ali20, Garcia-Valdecasas267, Armstrong49
Laser vs. traditional surgery
Steger743
Local anaesthesia in the wound
Patel592, Adams9, Russell659, Ure798, Johansson355, Alexander19, Sarac679
Intrapleural local anaesthesia
Aguilar13, Blake94, Frank240, Frenette250, Kastrissios380, Oxorn583, Rademaker625, Schroeder695, Scott701, Strömskag757,VadeBoncouer799
Local anaesthesia above the lobe of the liver
Chundrigar141, Joris361, Mraovic537, Pasqualuci590, Pasqualucci591, Rademaker624, Raetzell626, Scheinin684, Szem762, Weber823
Intercostal local anaesthesia
Blake94, Ross650
Epidural anaesthesia/morphine
Hakanson298, Huang336, Scott701, Thörn779
Transcutaneous electric nerve stimulation
Laitinen425
Preoperative and intraoperative analgetics
Forse236, Lane428, Michaloliakon519, Wilson847
Suprahepatic drain
Jorgensen360
Reduction of nausea/discomfort postoperative
Cabrera123, Fujii256, Sohi867, Steinbook744, Thune782
Special circumstances associated with laparoscopic surgery
CO2 vs. abdominal-lift
Kitano401, Koivusalo406, Koivusalo407, Lindgren456, Meijer509, Yoshida858
218
CO2 vs. helium
Bongard99
French vs. American method
Kum419
Clinical series covering symptoms and indication for treatment
This chapter contains a detailed breakdown of clinical series covering
symptoms and indications for gallstone treatment. The tables are summarily treated in the main report.
TABLE 1
Association between symptoms and gall stones in population studies. The studies represent
well-defined population groups that have been screened for gallstones by X-ray or ultrasound.
Only series covering more than 100 persons have been included.
The occurrence of gall stones is associated with
Author
Country
840
N
Biliary pain a
c
Pains in upper abdomen
Dyspepsiab
Wilbur
USA
1,233
Nej
Yes
Yes
Price620
UK
204
-
No
No
Sampliner677
USA
395
-
Yes
No
-
c
No
No
Noc
-
No
No
57
Bainton
UK
956
GREPCO39
Italy
1,081
Janzon352
Sweden
424
-
No
Barbara62
Italy
1,911
Yes
-
No
Pixleyd 611
UK
242
-
No
No
GREPCO42
Italy
1,239
No
-
No
Mellström511
Sweden
109
Yes
-
-
Glambek275
Norway
1,329
-
No
No
Jørgensen368
Denmark
3,416
No
No
No
Heatone 315
UK
1,896
Yes (women)
No (men)
Noc (women)
No (men)
-
Loria460
Italy
1,807
Yes
-
Yes
Attili53
Italy
29,739
Yes
-
-
a: Biliary pain is defined differently in different studies, and in certain studies are not defined at all. The Italian studies agree on the following definition: Pains in the epigastrium or upper right quadrant within the last five years. The pains must last more than half an
hour and must not by eased by bowel movements/flatus.
b: Dyspepsia involves a whole series of symptoms like nausea, heartburn, eructation of acid fluid, bloatedness, rumbling, pressure in the
epigastrium, flatulence and food intolerance.
c: A distinct tendency towards a link between symptoms and gallstones but the link is not significant.
e: Heaton’s work was considered as two studies (men and women).
219
TABLE 2
Relationships between symptoms and gallstones in consecutive patient cohorts referred to an
X-ray department or a clinical department. Only series involving more than 100 patients were
included.
The occurrence of gall stones is associated with
Author
Country
328
Hinkel
N
Biliary pain a
Pains in upper abdomen
Dyspepsiab
No
1,000
Yes
Yes
Koch404
USA
655
-
-
No
Wegge824
Denmark
192
-
Yes
Yes
Persson604
Sweden
817
-
Noc
Nod
No
185
Diehl
USA
300
Yes
Yes
Galatola263
UK
282
Yes
-
-
Farrell217
Ireland
300
-
Yes
Nejd
a: Biliary pain is defined differently in different studies, and in certain studies are not defined at all.
b: Dyspepsia covers a whole string of symptoms such as nausea, heartburn, eructation of acid fluid, bloatedness, rumbling, pressure in
the epigastrium, flatulence and food intolerance
c: The occurrence of abdominal pains was not different in people with and without gallstones, but maximal pain in the upper right quadrant was seen significantly more often in patients with gallstones than in patients without gallstones
d: A significant negative association between gall stones and certain dyspeptic symptoms
220
TABLE 3
Clinical series studying the frequency of persistent symptoms after cholecystectomy. The series
are consecutive with a follow-up of at least 3 months and a response rate of at least 70% a.
Follow-up has to have been conducted on at least 50 patients.
Persistent symptoms
Author
Burnett
Country
119
N/nb
Follow-up months
Painsc
Dyspepsiac
UK
200/141(o)
12-60
14%
11%
Rhind640
UK
72/66 (o)
12-
38% (17%)
40% (9%)
Gunn295
UK
107/105 (o)
12-24
23%
(7%)
-
Bremner107
UK
207/207 (o)
8-35
8%
(5%)
-
356
Johnson
UK
108/108 (o)
3-39
-
Ros649
Spain
130/92 (o)
24
22%
24%
Gilliland273
USA
650/525 (o)
15-79
12%
25%
Jørgensen376
Denmark
122/115 (o)
6-12
21%
Batesd, 70
UK
292/278/274 (o)
12 & 24
34%/27%
Paul595
Germany
60/51 (o)
4
18%
18%
Mühe547
Germany
94/93 (l)
136/130 (o)
49-67
27%
25%
-
Konsten409
HongKong
351/325 (o)
120
19%
-
Qureshi622
Ireland
100/100 (l)
12
13%
20%
Wilson846
UK
115/100 (l)
200/167 (o)
14
28
6%
7%
-
Mort531
USA
372/312 (o)
3
20-36%
-
Stiff
UK
250/205 (l)
200/155 (o)
15
32
37% (3%)
41%(10%)
-
Fenster223
USA
225/164 (l)
3
18%
54%
Kane378
USA
2.490/72% (l)
958/72% (o)
6
6
23% (11%)
24% (11%)
-
Ure797
Germany
508/468 (l)
15-23
26%
-
749
54% (30%)
(7%)
(6%)
> 50%
(o): Traditional open cholecystectomy; (l): Laparoscopic cholecystectomy
a: A number of works have been omitted because of lack of information about the follow-up, follow-up rates below 70% 59, 96, 651, 742, 750,
insufficient follow-up periods (5-7 weeks)92 or selected follow-up468, 516 omitting patients converted to open cholecystectomy
b: N/n: Number of patients at the start of the study/number of patients followed up
c: The proportion with persisting symptoms (the proportion with unchanged or aggravated conditions).
d: Follow-up after 1 and 2 years respectively.
221
Epidemiological surveys of possible differences in treatment indication
TABLE 4
The proportion of people with cholecystectomy among people with gallstone diseases
(gallstones or previous cholecystectomy) in different countries. All population studies covering
at least 50 people with gallstones were included.
Cholecystectomy rate a
Country
Gender
Age
Period
%
(N)
Norway276
Both
20-69
1983
5%
(300)
USA492
Men
20-74
1982-84
17%
(-)
Czechoslovakia863
Both
20-59
1989-90
19%
(262)
Denmark365, 375
Men
30-70
1982-84
23%
(142)
UK (Bristol)315
Men
40-69
1987-89
24%
(58)
UK (Oxford)612
Women
40-69
1982-84
28%
(156)
Ex-GDR 83
Men
15-
1986-87
31%
(181)
Czechoslovakia86
Women
15-92
?
31%
(-)
Italy (MICOL)53
Men
30-69
1984-87
32%
(1,511)
Italy (Sirmione)62
Men
18-65
?
32%
(59)
Ex-GDR
Women
15 -
1986-87
35%
(452)
Italy (Rome)39
Women
20-64
1980
35%
(102)
Italy (Rome)41, 42
Men
20-69
1982-84
36%
(102)
Itay (Sirmione)62
Women
18-65
?
39%
(151)
Denmark365, 375
Women
30-70
1982-84
39%
(256)
Italy (Sezze)40
Women
20-69
1984
41%
(68)
UK (Bristol)315
Women
25-69
1987-89
44%
(85)
USA492
Women
20-74
1982-84
44%
(- )
Italy (MICOL)53
Women
30-69
1984-87
44%
(2,603)
USA (Texas)304
Women
15-74
1985-86
45%
(155)
Sweden (Gothenburg) 511
Women
77-78
1984
47%
(55)
USA492
Women
20-74
1982-84
47%
(-)
Sweden (Malmoe) 352
Women
48, 53
1979
49%
(84)
Italy (Chianciano)460
Women
15-65
1985-86
50%
(70)
Sweden (Stockholm)539
Women
40, 60
1992
54%
(54)
USA492
Women
20-74
1982-84
55%
(-)
83
a: People with cholecystectomy/(people with cholecystectomy + people with gallstones)
222
Postoperative pain, hospital stay and convalescence
TABLE 5
Postoperative pain, length of hospital stay and convalescence in randomised trials of different
forms of access to cholecystectomy
Study
N
Blinding
Pain
Analgesia
Hospital stay
(days)
Absence due to
illness (days)
Laparoscopy vs. traditional open laparotomy
Ortega579
20
Yes
5 vs. 12 a
Trondsen789
72
No
Sign.a
Berggren79
30
No
Huang
337
29
No
-
-
1,2 vs. 1,1
4 vs. 6b
125mg vs. 200mg c
0,5 vs. 2
b
-
2 vs. 4
11 vs. 34
1,8 vs. 2,8
12 vs. 24
3,9 vs. 7,9
-
Laparoscopy vs. minilaparotomy
Majeed483
200
Yes
McMahon504
302
No
McGinnee 500
310
No
-
30
No
-
Seenu703
181
No
-
Schmitz690
130
No
40 vs. 59 a
22mg vs. 40mg d
-
3 vs. 3
35 vs. 28
2 vs. 4
38 vs. 38
4 vs. 3
-
3 vs. 5
-
2,6 vs. 4
-
Minilaparotomy vs. open laparotomy
O’Dwyer574
Not sign.
2,5 vs. 4,5 b
Not sign.
Significant differences are written in italics
a: Visual analogue scale – significantly greater pain after open laparotomy
b: Median number of painkilling injections
c: mg of pethidin 13-24 hours after operation. Not sign. from 0-12 hours after operation
d: Median volume morphine
e: McGinn only treats the length of hospital stay according to the "intention to treat" principle
Number of biliary tract lesions in connection with cholecystectomy
In general, the following requirements were stipulated for all surveys:
❖
Consecutive groups of 200+ patients.
❖
Evenly distributed patient material (e.g. not only elderly patients or only young
patients).
❖
The material has to be well described.
❖
Biliary tract lesions have to be well described.
Any deviations will be stipulated in the text accompanying the individual
tables.
The following types of works are differentiated:
❖
Clinical series, in which one or more hospital departments or surgeons record their
own results. Randomised trials are included, if the randomisation does not cover different surgical technologies, and if it is clearly stated that all patients were included.
223
❖
Questionnaire surveys involving departments or surgeons.
❖
Regional or national results in the form of continuous reports to a register or a questionnaire survey that covers a well-defined geographic area.
❖
Audits, during which the case histories were studied by an external expert group.
TABLE 6
Clinical series covering traditional open cholecystectomy without choledochal exploration.
Author
Period
N
Bile duct complications
Pasquale589
1985
247
0
2 (0,81)
Monson525
1984-88
479
0
0
Chaudary132
Acute
Age in yearsb Comments
Central (%) Peripheral (%) cholecystitis (%)
12,5
1986-89
340
0
0
0
Stahlschmidt736 1984-87
861
0
-
17
55
Warwick816
1981-88
384
0
0
24,4
52
450
1979-84
494
0
0
0
50
214
Ewing
1988-89
400
0
4 (1,00)
31
-
Konsten409
1978-80
351
0
-
12,8
56 (17-87)
Meyer518
1983-90
500
0
-
23
54 (16-98)
Brune114
1983-90
748
2 (0,27)
-
-
4,804
2 (0,04)
6 (0,26)b
Lewis
Sum
15,6%
a: Median or mean (range)
b: N=2344
c: Included even though these are randomised trials since they include consecutive series
224
51 (-)
RCT of drain treatmentc
34 (12-76)
-
RCT of drain treatmentc
TABLE 7
Clinical series covering traditional open cholecystectomy in which it is not possible to
differentiate between simple cholecystectomy and cholecystectomy with choledochal surgery
Author
Period
N
Bile duct complications
Acute
Age in yearsb Comments
Central (%) Peripheral (%) cholecystitis (%)
Ganey264
1978-83
1,035
0
0
16
Scher685
1979-82
432
0
1 (0.23)
-
-
Gregg292
1979-80
765
1 (0.13)
-
-
-
Heberer316
1985-87
544
-
0
-
Orth868
1982-89
773
1 (0.13)
2 (0.26)
0
56
1986-90
346
2 (0.58)
-
-
-
Kocher
1984-87
1,631
Saltzstein674
1988-90
500
Caputo126
1980-87
1,617
7 (0.43)
1 (0.06)
25.2
-
Clavienb, 145
1984-89
1,252
0
2 (0.16)
0
52 (16-88)
Cox159
1985-89
457
1 (0.22)
-
36.4
53 (12-87)
Davies175
1985-90
722
0
0
24.9
49
Herzog325
1984-90
1,631
1 (0.06)
-
15
-
Morgenstern529 1982-88
1,200
Battersby72
405
0
(15-92)
1 (0.06)
2 (0.12)
15.5
58 (15-91)
0
0
29.8
40 (10-96)
2 (0.17)
-
-
56 (3-96)
1989-90
304
0
-
38.3
53
Wieden
1985-89
921
3 (0.33)
1 (0.11)
-
-
Bradbury105
1989-90
246
0
0
-
48k/57m
Bjerkeset91
1980-89
832
1 (0.12)
-
49
66 (18-100)
20 (0.13)
9 (0.10)c
19.4%
Stoker752
839
Sum
15,208
The damage occurs during cholangiography
a: Median or mean (range)
b: Two publications 117, 512 make up a subset of Clavien 145 and have, therefore, been omitted.
c: N=9129
225
TABLE 8
Cholecystectomy by minilaparotomy. Clinical series and randomised trialsa.
Author
Period
N
Bile duct complications
Acute
Age in yearsb
Comments
Central (%) Peripheral (%) cholecystitis (%)
Dubois197
1973-80
Goco282
15 month
Morton532
2 years
Salembier671
-
Merrill514
3 years
91
0
0
28,8
57 (16-84)
Reddick469
1988-89
25
0
0
-
40
1986-90
200
0
0
55
0
0
Ledet
435
1.500
0
0
-
-
56
0
0
-
-
96
0
0
-
-
125
0
0
-
-
-
(21-82)
Part of RCT
(16-82)
O’Dwyer870
-
Safatle666
1990-91
21
0
0
-
-
Stage733
-
24
0
0
-
56 (22-72)
Barkun65
1990-91
25
0
1 (4.00)
-
-
Part of RCT
Kunz421
1990- ?
37
1 (2.70)
0
-
-
Part of RCT
O’Dwyer574
-
16
0
0
31,3
46 (27-74)
Part of RCT
Pélissier598
1983-90
191
0
0
-
46 (9-82)
Suarez758
1984- ?
50
0
0
48
47 (-)
Warren
815
-
48 (13-81)
Not “int. to treat”
1990-91
20
0
0
-
55 (30-81)
Assalia51
18 months
24
0
0
-
60 (-)
Part of RCT
Coelho148
1992
15
0
0
-
43 (25-66)
Part of RCT
Rozsos656
1990-93
607
1 (0.16)
1 (0.16)
-
-
Seenu703
1990-92
97
0
0
-
-
Tyagi793
-
143
0
4 (2.80)
-
McGinn500
1991-95
155
0
1 (0.65)
0
57 (26-84)
Gaetini261
1992-94
62
0
0
-
-
Kumar871
1995-96
60
0
0
0
39 (24-70)
Part of RCT
Schmitz690
1991-94
65
0
0
-
53 (24-66)
Part of RCT
Sum
3,760
2 (0.05)
7 (0.19)
14.8%
Sum >= 50
3,553
1 (0.03)
6 (0.17)
14.0%
Sum >=100
2,921
1 (0.03)
6 (0.21)
0.0%
Sum >=200
2,307
1 (0.04)
1 (0.04)
-
-
(15-87)
Part of RCT
(20-83)
Part of RCT
In this material, series covering less than 200 patients were also accepted because relatively little has been written about the subject. The
complication rates were, however, calculated on materials of more than 50, 100 and 200.
a: Two randomised trials were not included483, 504, since they are part of a separate assessment. The rest of the randomised trials do not
live up to the requirements of sufficient randomisation. They are included as clinical series.
b: Median or mean (range).
226
TABLE 9
Laparoscopic cholecystectomy. Early clinical series, published 1990-92.
Author
Period
N
Bile duct complications
Acute
Age in yearsb
Comments
Central (%) Peripheral (%) cholecystitis (%)
Duboisb, 200
1988-90
690
3 (0.43)
2 (0.29)
-
-
Bailey56
1989-91
375
1 (0.27)
5 (1.33)
6.4
47 (16-94)
Corbitt155
-
300
0
0
16
(15-90)
Cuschieri168
-
1,236
4 (0.32)
2 (0.16)
2.3
47 (13-86)
Fitzgibbon231
-
350
0
0
14.7
-
Graves290
1989-90
304
1 (0.33)
0
3.3
50 (14-83)
Ko403
1989-91
300
1 (0.33)
0
5.3
(12-85)
Manger486
1990-91
200
0
1 (0.50)
3.0
47 (13-78)
Peters607
1990
283
1 (0.35)
3 (1.06)
4.9
46 (-)
Sackier 662
1989-90
516
1 (0.19)
1 (0.19)
-
-
Spaw728
-
500
0
1 (0.20)
5.8
46 (17-86)
Voyles812
-
453
0
1 (0.22)
23.4
52 (15-98)
Wolfe852
1990-91
381
0
4 (1.05)
7.6
45
Baird58
1989-91
800
0
3 (0.38)
13.0
-
Dallemagne170
1990-91
368
1 (0.27)
1 (0.27)
1.6
56 (-)
Dashow173
1990-91
250
0
2 (0.80)
-
49 (15-97)
Davis176
1989-
622
1 (0.16)
1 (0.16)
10.0
48 (17-97)
Dion189
1990-91
258
0
1 (0.39)
1.2
44 (14-82)
Fabre215
1989-91
392
4 (1.02)
0
16.6
54 (17-85)
Feussner226
-
500
0
4 (0.80)
-
-
Fielding228
1990-91
220
0
1 (0.45)
6.8
-
Frazee
245
1990-92
706
2 (0.28)
-
14.2
51 (-)
1990-91
340
0
1 (0.29)
6.8
49 (16-87)
Graber288
-
300
4 (1.33)
-
-
-
Hawasli313
1989-91
480
0
2 (0.42)
-
-
Hershman323
-
200
1 (0.50)
2 (1.00)
24.5
49 (19-86)
Herzog325
1990-91
278
1 (0.36)
1 (0.36)
0.0
53 (18-86)
Huang335
1990-91
200
1 (0.50)
1 (0.50)
15.5
51 (27-83)
Kimura398
1990-91
250
0
0
0.0
49 (24-78)
Kiviluoto402
1991-92
200
1 (0.50)
0
16.0
48 (16-83)
Kozarekc. 411
1990
597
11 (1.84)
6 (1.01)
-
-
Leahy433
1990
308
1 (0.32)
4 (1.30)
13.6
48
Lillemoe453
1989-91
400
2 (0.50)
5 (1.25)
2.5
48 (15-96)
Miles521
-
201
1 (0.50)
1 (0.50)
-
-
Nottle569
1990-91
280
0
3 (1.07)
-
-
Pérrisatd, 602
1988-91
696
3 (0.43)
4 (0.57)
-
Ratliff633
1990-91
230
0
2 (0.87)
20.0
56 (10-86)
Scott697
1990-91
210
0
1 (0.48)
11.4
46 (17-85)
Sigman711
1990-?
500
2 (0.40)
-
9.1
48 (7-93)
1990
271
1 (0.37)
-
-
-
Sim
Personal series
(12-75)
Gai262
712
7 depts. in 3 countries
in Europe
Personal series
(13-83)
227
(Tabel 9 continued)
Bile duct complications
Acute
Age in yearsb
Author
Period
N
Singson714
1990-91
329
0
4 (1.22)
9.1
47 (15-83)
Soper724
1989-91
618
2 (0.32)
1 (0.16)
6.0
47 (15-82)
Stahlschmidte, 736 1990-92
812
3 (0.37)
6 (0.74)
-
-
Stoker752
1990-91
280
0
1 (0.36)
27.5
51 (-)
Troidlf, 787
1989-91
400
3 (0.75)
0
2
52 (18-87)
Wayand821
1990-91
250
1 (0.40)
2 (0.80)
19.2
52 m/46 k
Wieden839
1990-91
600
4 (0.67)
1 (0.17)
6.1
-
62 (0.32)
81 (0.46)g
Comments
Central (%) Peripheral (%) cholecystitis (%)
Sum
19,234
8.9%
a: Median or mean (range)
b: An earlier publication199 contains a subset of this material
c: 13 of the 17 lesions occurred during surgeons' first 20 operations
d: Includes a large proportion of the patients from another series151, which has, therefore, been excluded
e: 3 bile duct lesions is a minimum number, since the 6 other lesions probably includes at least one bile duct lesion
f: Includes an earlier publication by the same author787.
g: N=17.457
A study covering 1,009 patients717 includes 6 injuries (0.59%), but it cannot be determined whether they are central or peripheral
228
TABLE 10
Laparoscopic cholecystectomy. Clinical series published 1995-97 a
Author
Period
N
Bile duct complications
Acute
Age in yearsb
Comments
Personal series
Central (%) Peripheral (%) cholecystitis (%)
Amaral23
1991-92
200
0
1 (0.50)
24.0
46 (-)
Azurin55
1990-95
1,400
0
2 (0.14)
27.0
-
Denning180
1990-92
894
3 (0.34)
4 (0.45)
-
-
Dorazio195
1990-94
1,344
1 (0.07)
-
-
(9-90)
Dubois201
1988-94
2,665
6 (0.23)
13 (0.49)
12.5
51 (6-90)
Dubois196
1990-93
500
2 (0.40)
8 (1.60)
13.2
45
333
-
Hölbling
1992-94
455
2 (0.44)
1 (0.22)
11.0
-
Madhavan476
1990-91
400
0
-
30.0
53 (9-90)
Panton587
1991-93
228
0
4 (1.75)
18
50 (15-84)
Schrenkc, 694
1990-93
1,300
3 (0.23)
-
-
-
Slim716
1989- ?
710
4 (0.56)
0
7.9
57 (17-93)
Bond98
1990-93
529
4 (0.76)
3 (0.57)
4
44 (13-85)
Buanes115
1991-94
277
0
4 (1.44)
6.9
46 (18-83)
Carrolld, 129
1989-95
3,242 12 (0.37)
-
-
Chen135
1991-95
2,428
0
Ferzli
225
5 (0.21)
-
1
(15-77)
1990-4
1,442
2 (0.14)
2 (0.14)
-
44 (13-94)
Kullman416
1991-94
630
4 (0.63)
3 (0.48)
-
53 (11-86)
Leung443
1990- ?
297
1 (0.34)
1 (0.34)
22.6
53 (-)
Zisman862
-
329
0
-
-
-
Dexter182
1990-94
411
0
4 (0.97)
-
53 (-)
Jan349
1991-95
1,115
5 (0.45)
3 (0.27)
Ladocsi422
1991-93
734
1 (0.14)
-
Lam427
1994-96
213
0
-
-
-
Mjåland524
1994-95
200
2 (1.00)
1 (0.50)
-
49 (17-82)
Taylor768
1990-95
2,038
2 (0.10)
-
-
-
774
1991-95
361
4 (1.11)
4 (1.11)
31
50 (16-85)
24,342 63 (0.26)
58 (0.39)e
Thanh
Sum
a:
b:
c:
d:
e:
-
47 (28-70)
12.1
49 (-)
12.7%
The search for relevant literature ended in November 1997
Median or mean (range).
Counts only injuries that lead to conversion (does not look at injuries not discovered until after the operation).
): The series includes an earlier publication528, which has, therefore, been excluded
N=14.742
229
TABLE 11
Laparoscopic cholecystectomy. Results from questionnaire surveys.
Author
Period
Airan14
-91
N
Bile duct complications
Acute
Central (%) Peripheral (%)
cholecystitis (%)
Age in yearsa
Comments
2,671
5 (0.19)
25 (0.94)
-
52 m/45wb
Response rate not
stated
Delaitre179
-
6,512
29 (0.45)
18 (0.28)
-
51 (13-95)
questionnaire and
seriesc
Larson432
-
1,983
5 (0.25)
7 (0.35)
-
-
d
1990-92
5,927
12 (0.20)
-
-
74% response rate
-92
9,597
27 (0.28)
69 (0.72)
-
-
e
77,604 317 (0.41)
Cocks
147
Devency181
Deziel
183
142 (0.18)
-
-
41% response rate
Kimura400
1990
1990- ?
1,989
9 (0.45)
1 (0.05)
0
-
f
Croce162
1990-92
6,865
18 (0.26)
-
-
g
203
Dunn
1990-91
3,319
11 (0.33)
35 (1.05)
-
Response rate not
stated
Mucio538
1990-91
2,399
6 (0.25)
10 (0.42)
22
-
72% response rate
Trondsen790
-
527
3 (0.57)
5 (0.95)
5.3
-
7 departments
VincentHamelin807
1989-92
2,432
11 (0.45)
5 (0.21)
7.7
50 (9-91)
Response rate not
stated
Morino530
-
2,127
8 (0.38)
-
Pongchairerks618 -
1,744
14 (0.80)
11 (0.63)
Collet150
4,624
7 (0.15)
130,320 482 (0.37)
Sum
1994
-
-
-
-
25.9
56m/53wb
i
16.2%
328 (0.30)
h
One questionnaire survey covering 36,232 patients15 has not been included in the table, since it was impossible to differentiate between
central and peripheral bile duct lesions (a total of 0.50%).
a: Median or mean (range).
b: m=men, w=women
c: Two questionnaire surveys linked to three clinical series.
d: No information about how the surgeons were chosen and how many declined to participate.
e: Questionnaire for surgeons and surgical managers in Oregon. Response rate 69% and 53%, respectively.
f: Eight institutions. How they were chosen and what response rate was achieved are not described in detail.
g: 19 groups. How they were chosen and what response rate was achieved are not described in detail.
h: 150 surgeons. It is not stated how many were asked.
i: N=110,777
230
TABLE 12
Laparoscopic cholecystectomy. Regional or national registers/questionnaire surveys
Author
Period
N
Bile duct complications
South. Club43
-
1,518
8 (0.53)
-
Litwin458
1990-91
2,201
4 (0.18)
759
1989-92
3,606
Go280
1990-92
Orlando577
Age in yearsa Comments
Acute
Central (%) Peripheral (%) cholecystitis (%)
9.6
47 ( 8-98)
Degree of coverage?
USA
10 (0.45)
-
-
Canada
25 (0.69)
-
-
-
Degree of coverage?
France
6,076
52 (0.86)
-
-
-
100% coverage
The Netherlands
1990-91
4,640
15 (0.32)
-
15.1
-
97% coverage.
USA
Schlumpf688
1989-92
3,722
20 (0.54)
11 (0.30)
10
50 (13-97)
100% coverage.
Switzerland b
Wayand822
1991
7,351
34 (0.46)
-
-
-
100% coverage. Austria
Kum420
1990-92
1,066
10 (0.94)
-
6.5
-
95% coverage.
Singapore
-92
4,000
13 (0.33)
28 (0.70)
-
-
> 70% coverage
New Zealand c
Buanes116
1993-94
1,699
9 (0.53)
15 (0.88)
-
-
National Registerd,
Norway
Hjelmquist329
-
11,164
57 (0.51)
-
-
-
Sweden
Moore526
-
8,839
15 (0.17)
-
-
-
Degree of coverage?
USA
Ovaska581
1992-94
5,742
56 (0.98)
18 (0.31)
4.2
51 (12-90)
National Register,
Finland
Regöly-Mérei636 1991-94
26,440
109 (0.41)
39 (0.15)
-
-
Hungary e
Russell658
1990-93
15,221
38 (0.25)
-
19.2
-
Connecticut, USA
1991-94
7,654
57 (0.74)
-
-
-
National Registerf,
Denmark
110,939 522 (0.47)
121 (0.28)g
Suc
Windsor848
10
Adamsen
Sum
14.2%
a: Median or mean (range).
b: Parallel publication 687
c: Surgeons and endoscope operators from the whole of New Zealand were surveyed. See also [849], in which only the surgeons were
questioned.
d: Also stipulates injury during simultaneous open surgery.
e: National questionnaire survey with 95% response rate. The survey partially overlaps with the period of an earlier survey (1990-93),
which also consisted of a questionnaire sent to all departments in Hungary 343. On that occasion, the complication rate for central
biliary tract injuries was 0.59%.
f: No decline in the number of complications has been identified over time.
g: N=43,804
231
TABLE 13
Laparoscopic cholecystectomy. Audit
Author
Period
N
Birdi88
1990-92
555
1 (0.18)
Wherry838
1990-92
5,642
32 (0.57)
Steele740
1991-94
502
6 (1.20)
Richardson642
1990-95
5,913
37 (0.63)
Wherry837
1993-94
9,130
35 (0.38)
Merrie513
1991-95
929
8 (0.86)
22,671 119 (0.52)
c
Sum
Age in yearsa Comments
Bile duct complications
Acute
Central (%) Peripheral (%)
cholecystitis (%)
5 (0.90)
-
51 (16-85)
one town
-
-
-
US-army
3 (0.60)
-
-
one department
-
-
-
West of Scotlandb
50 (0.55)
-
-
US-army
5 (0.54)
-
-
New Zealand
63 (0.57)
a: Median or mean (range).
b: The results of the first 1,683 cases from the period 1990-92 were published 257 and the proportion suffering central complications was
0.48%.
c: N=11,116
232
Results for cholecystolithotomy
TABLE 14
Clinical series of cholecystolithotomy (elective surgery). Only series involving more than
25 patients were included
Author
Period
N/na
Studyb
Successc Follow-up
Persistent
pains
Comments
Recurrence
Months
(median)
Pers603
1915-37 667/504 o
-
-
21%
236
Gibney270
1983-87 63/48
o
-
11%
27%
18
After acute cholecystitis
Hamilton301
-
25/
m
96%
12%
8%
8 (4-18)
Local anaesthetic
-
26/
l
96%
-
-
-
Local anaesthetic
8% biliary fistula
-
81/62
l
81%
5%
10%
18 (5-36)
Intercostal/
epidural anaesthesia
Kellett385
-
46/
ll
91%
-
-
-
4% biliary leak
Akiyama17
1981-89 28/
ll
71%
-
5%
36
7% biliary leak/
7% cholecystectomy
Chiverton140
1986-89 60/
ll
93%
2%
0%
3
3% biliary leak
Stage734
1990-91 32
ll
90%
-
-
-
3% biliary fistula
Tóth783
1989-90 40
ll
98%
-
-
-
CheslynCurtis138+
Gillams272
1988-90 113/
ll
88%
Picus609
1987-91 58
ll
97%
-
-
Donald193
1988-90 100
-
-
-
McDermott498
1988-91 37/31
ll
86%
1987-92 /65
-
-
?
Leahy
434
Majeed482
Courtois
87
Bing
157
421/
21% (7%)
10%
14
Bile accumulation (4%),
perforated gall bladder
(2%)
-
Local anaesthesia
7% biliary leak
44%
48
Follow-up from
Cheslyn-Cutis92
13%
16%
4-46
Bile salts afterwards
-
12%
40%
33/14
See 609
97%
-
-
-
Chinese – only abstract
a: N and n represent the number of patients included and the number of patients at follow-up, respectively.
b: ): o =open surgery, m=minilaparotomy, l=laparoscopy, ll=laparoscopy plus laser, ultrasound or other form of pulverization.
c: Proportion who have stones removed.
233
TABLE 15
Clinical series involving contact dissolution (elective treatment). Only series involving more
than 25 patients were included.
Author
Period
N/na
Studyb
Successc Follow-up
Comments
Persistent
pains
Recurrence
Months
(median)
Thistle778
-
75/
po
50%
(96%)
7%
19%
6-16
No serious side effects
Hellsternd,
-
170/
po
2/3
-
-
-
4% biliary leak
-
36/
nbe
60%
-
-
-
3% perforation of cysticus
William
-89 75/
po
(92%)
10%
-
6-35
0% biliary leak/average
length of treatment
12.4 hours
Leuschnerd,
-90
po
61%
(97%)
-
-
-
5% biliary leak
318, 319, 320
Soehendra719
841
209/
444, 445, 446
McNulty506
1989-90 25/
po
72%
-
22%
6-18
4-30 h
StabenowLohbauer732
1989-90 30/
po
nb
53%
54%
-
-
-
median
duration of treatment
7 hours
Salamon669
1989-91 69/
po
86%
-
-
-
somnolens
median duration 12 hours
Eidsvoll
1989-92 25/
po
79%
33%
53%
16
Janowitz351
-
42
pof
29%
-
-
-
Morgan527
-
25/
po
60%
-
-
-
16% biliary leak
Pauletzki596
-
/60
po
70%
42
Actuarial method
a:
b:
c:
d:
e:
f:
234
d, 207, 208
Refers to the number of patients included and the number of patients at follow-up, respectively
po= percutaneous dissolution , nb=dissolution by naso-biliary probe.
The gall bladder is emptied of stones (or is almost emptied (>95%) of stones).
One or more parallel publications. Leuschner and Hellstern also present internally overlapping material
Combined with ESWL
Uses either MTBE or MTBE+EDTA at respectively low and high Haunsfield units of the gallstones
Study of cholecystectomy in patients with acalculous biliary pain
TABLE 16
Clinical series covering cholecystectomy for gallstone-like pains in patients without gallstones
(acalculous biliary pains). Only series with a follow-up rate of at least 70% were included a.
Author
Country
N/nb
Follow-up
monthsc
Nechis551
USA
18/18
1-60
(5%)
CCK-test
Madsen479
Denmark
9/9
32 (13-36)
33% (22%)
CCK-testf
Canada
41/37
18
32%
(3%)
CCK - bileg
6%
(0%)
CCK in some
-
(0%)
CCK (not emptied)
20%
(7%)
CCK - bile
121
Burnstein
628
Persistent
painsd
-
Rajagopalan
USA
21/16
22
Nora567
USA
30/30
-
Einarsson209
Sweden
15/15
9-27
Ferraris224
USA
42/38
6-?
29%
(-)
Rhodesh, 641
UK
90/81
35 (12-66)
33%
(9%)
Gilliland274
USA
60/43
47 (16-79)
23%
(- )
31%
Westlake
836
(12-39)
Canada
26/26
25
Zech860
USA
60
12
Halverson300
USA
12/11
12-69
Middleton520
UK
34/34
20
(3-36)
Sorenson725
USA
11/11
10
(2-17)
Watson819
Australia
14/14
Jones358
USA
36/35
14
(5-48)
5%
clinic
CCK - pain
CCK
HIDA-EF
(2%)
18%
(2-40)
Preoperative
physiological
measuremente
CCK-EF
CCK-EF < 35%
6%
EF < 35%
- ( 0%)
EF <35%
7%
(0%)
Dependent on EFi
-
(9%)
Dependent on EFi
(a): Two studies were not included since the requirements set were not fulfilled255, 317
N and n represent the number of patients included and the number patients at follow-up, respectively
Median or mean (range)
Persistent pains (pains of same strength as before the treatment or worse)
The physiological measurement mainly consists of CCK (cholecystokinin) stimulation, in which the measurement of the effect is either
the level of pains or the degree of emptying of the gall bladder. In recent years, there has been a consensus that an EF (ejection
fraction) under 35% is pathological.
f: T he two who had unchanged pains both had positive provocative tests
g: Had examined both contraction and crystals. The one with unchanged pains was negative as far as the above mentioned tests are
concerned.
h: Two studies by Lennard440, 441 are omitted since they are a part of Rhodes641
i: The proportion of patients with persistent pains was smallest with pathological EF.
Before 1978, 16 surveys27, 28, 161, 204, 212, 247, 278, 284, 286, 296, 384, 472, 541, 542, 637, 801 are reported in which physiological measurements were rarely taken to
verify whether the gall bladder was diseased. Freeman247 did, however, conduct cholecystokinin cholangiography to see whether the pain
could be reproduced at the same time as he measured the gall bladder contraction. Persistent pains in these series vary from 0-40%.
a:
b:
c:
d:
e:
235
Appendix 4
Statistical analyses
A NALYSIS OF DEVELOPMENTS IN SURGICAL RATES
The analyses of data from the National Hospital Discharge Register cover the period 1978-95. The period has been divided into four sub-periods: 1978-83, 1984-87, 1988-91 and 1992-95. This subdivision is justified in the methodology section of Chapter 2. Developments in the frequency of operations were identified by calculating age-standardised operation rates for the individual types of operations throughout the period
and by comparing age-related operation rates for each of the four subperiods. The analyses were based on the number of operations in 10-year
age-span groups for each calendar year compared with the overall size of
the population in the year in question. In all the analyses, men and women were analysed separately.
Age-standardised operation rates
The age-standardised operation rates were calculated using the 1995 population as the standard, i.e. on the basis of the age-related operation rates in the individual year, the expected frequency was calculated as if the
age composition had been the same as the age distribution of the whole
population (men and women) in 1995 (direct age-standardisation). By
using Dobson’s method192 95% safety margins were also calculated for
each year.
Age-related operation rates
If developments in the frequency of operations differ in the different age
groups, the age-standardised curves will conceal important information
about the developments. Therefore, age-related operation rates have also
been calculated for each of the four sub-periods. The number of operations in the individual age groups was relatively modest, which can cause
significant random fluctuations from age group to age group. Consequently, the curves need to be ‘smoothed out’ using a statistical model. The
statistical model also makes it possible to test the differences in the frequency of operations between the four sub-periods.
236
Statistical model
The number of operations in age group a and period p is assumed to be
Poisson distributed by the mean value m. The correlation between frequency of operation, age and period is then described by the following basis model for men:
log µ = k + α1 a + α2 a2 + α3 a3 + β p + λ1 a p + λ2 a2p + log (nap), where
where k is the constant, , α1 – α3 are parameters indicating age, β the period and λ1 and λ2 are parameters indicating an eventual interaction between age and period. If both λ1 and λ2 are 0, the development during the
four time-periods is the same in different age-groups. nap indicates the
number of persons in the various age-groups in the four time-periods and
is used as a so called offset. The model is a third degree polynomium, as
age is included to the third power. Age is in years and used as a continuous variable, whereas period is included as a categorical variable with
four classes.
In women the age dependent surgical rates are more complex, at prevalence of surgery is not constant increasing with age, but shows a
plateau between age 25 and 40. The model for women, therefore, includes two age parameters, one below and one above 40 years.
log µ = k + α1 a1 + α2 a12 + α3 a13 + κ1 a2 + κ2 a22 + κ3 a23 + β p + λ1 a1 +
λ2 a12 p + γ1 a2 p + γ2 a22 p + log(nap),
where a1 is age in years in women below or equal to 40, otherwise 0,
whereas a2 is age in years in women above 40, otherwise 0.
Besides this the model is completely parallel to the model for men, but
has two sets of age parameters and two sets of interaction parameters.
Backward elimination and likelihood ratio tests reduce the start model to a final model that only includes parameters with a significant effect on the frequency of operations. A 5% level of significance was used
in the tests.
An example of the analyses is shown below. The example refers to the
analysis of simple cholecystectomy for women. Figure 1 shows the agerelated frequency of cholecystectomy for women in the four sub-periods.
237
FIGURE 1
Observed rate for simple cholecystectomy – women
Rate per 100,000
260
240
220
200
180
160
140
120
100
80
60
40
20
0
Age 0
10
1978-1983
20
30
1984-1987
40
50
1988-1991
60
70
80
1992-1995
Table 1 shows the final model for cholecystectomy for women, i.e. the
model that only includes significant parameters. The final model reveals
a complicated association with age, a significant difference in the frequency of operations between the periods and a significant interaction between age and period (for both age parameters). Thus, developments in
operation rates were significantly different for the different age groups.
TABLE 1
Simple cholecystectomy – women, final model.
df
Chi-Square
P-value
Age1
1
840,1624
0.0001
Period
3
129,4166
0.0001
Age1*Period
3
81,7824
0.0001
Age12
1
441,1829
0.0001
Age13
1
284,0963
0.0001
Age2
1
729,2097
0.0001
Age22
1
509,4697
0.0001
Age2*Period
3
170,1024
0.0001
Age1: Age ≤ 40 and Age2: Age > 40
238
Table 2 tests how well the model describes the observed rates (model fit).
As the deviance/df is close to 1, the model prerequisites have almost been
met.
TABLE 2
Simple cholecystectomy – women. Test for model fit.
df
Chi-Square
Chi-Square/DF
Deviance
309
370.2908
1.1984
Pearson Chi—Square
309
1194.5825
3.8660
The fitted curve for the 1992-95 cholecystectomy rate has been inserted
in figure 2 along with the observed rates. The figure shows that the model is capable of describing the decrease in operation rates for women around 40. Table 3 shows the corresponding parameter estimates and table
4 tests whether the operation rates were identical in the four sub-periods.
FIGURE 2
Simple cholecystectomy – women. Model fit.
Rate per 100,000
200
180
160
140
120
100
80
60
40
20
0
Age 0
10
20
30
40
50
60
70
80
239
TABLE 3
Simple cholecystectomy - women. Estimated parameters.
Parameter
df
Estimate
Std. Err
Chi--Square
P-value
Intercept
1
-22.9421
0.6283
1333.4683
0.0001
Age 1
1
1.4442
0.0679
451.9523
0.0001
Period 1
1
-1.1327
0.1040
118.7091
0.0001
Period 2
1
-0.9029
0.1161
60.5060
0.0001
Period 3
1
-0.5472
0.1122
23.7926
0.0001
Period 4
0
0.0000
0.0000
-
-
Age1*Period1
1
0.0258
0.0030
73.8022
0.0001
Age1*Period2
1
0.0158
0.0033
22.3024
0.0001
Age1*Period3
1
0.0065
0.0033
3.9276
0.0475
Age1*Period4
0
0.0000
0.0000
-
-
Age12
1
-0.0425
0.0024
316.6298
0.0001
Age13
1
0.0004
0.0000
228.6763
0.0001
Age2
1
0.0407
0.0021
375.6272
0.0001
Age2
2
1
-0.0011
0.0000
493.7108
0.0001
Age2*Period1
1
0.0140
0.0013
111.9328
0.0001
Age2*Period2
1
0.0176
0.0015
146.3164
0.0001
Age2*Period3
1
0.0108
0.0015
52.1207
0.0001
Age2*Period4
0
0.0000
0.0000
.
.
Age1: Age <= 40 and Age2: Age > 40
TABLE 4
Simple cholecystectomy – women. Test for similarities between sub-periods
df
Chi-Square
P-value
Per1=Per2
3
55.0417
0.0001
Per2=Per3
3
91.7580
0.0001
Per3=Per4
3
231.6486
0.0001
Per1=Per2=Per3
6
268.0509
0.0001
Per2=Per3=Per4
6
467.2084
0.0001
Per1=Per2=Per3=Per4
8
710.4773
0.0001
Per1= period 1 etc.
Finally, figure 3 shows the estimated curves for all four sub-periods. The
model showed an interaction between age and period, which was revealed
in the figure as a very different age distribution in the four sub-periods.
240
FIGURE 3
Simple cholecystectomy – women
Rate per 100,000
210
180
150
120
90
60
30
0
Age 0
10
1978-1983
20
30
1984-1987
40
50
1988-1991
60
70
80
1992-1995
The model described was used for all types of operations. The smaller the
number of operations, the simpler the model, because only a few parameters were significant.
R EGIONAL VARIATIONS IN OPERATION RATES
Hospital areas
Sub-division into the four periods of time was used to help estimate the
regional variations. For each period, population-based operation rates
were calculated for geographic areas that correspond approximately to
the area covered by a given hospital. The areas were defined on the basis
of which hospital carried out the majority of the operations in question
in the municipality. Municipalities mainly served by the same hospital
constitute one area. The municipalities of Copenhagen and Frederiksberg
were considered as a single area covering several hospitals. The areas
were defined on the basis of all biliary tract procedures, but each of the
four sub-periods was calculated separately. If a hospital closed during
one of the periods, it was calculated along with the hospital that took
over the majority of its patients. The number of areas fell from 75 in
1978-83 to 53 in 1992-95 (table 5). The areas are listed in the appendix
(tables 9-12). As not all the patients in a given area were operated on in
241
the local hospital, the operation rate in the area cannot be ascribed solely to the activity in this hospital.
TABLE 5
Number of hospital areas for gallstone treatment during different periods.
Periods
Number of areas
1978-1983
1984-1987
1988-1991
1992-1995
75
75
65
53
Calculation of index for operation rates
Since the areas vary greatly in size and the statistical uncertainty, therefore, varies greatly, a so-called ‘random effect model’ was used which realigns estimated operation rates based on small numbers with the national
average. The relative differences in the frequency of operations are, therefore, cautious estimates of the regional variation.
Calculation of simple index without random effect
A simple age standardised operation index is calculated. If Oi is assumed
to be Poisson distributed, the standardised operation rate can be calculated as θi = Oi/Ei with a standard deviance of std (θi) = 1/ √ Oi , where Oi
is the observed number of operations in an area i and Ei is the expected
number, if operations rates were similar to the average in the whole country.
Calculation of index with random effect
In the model with random effect it is supposed that Oi is normal distributed with mean θi Ei.
If µi = θi Ei then the link function is log (µi) = log (Ei) + vi , where vi = log
(θi) is normal distributed N (0,σ2)271.
exp(vi) shows the estimates for the operation index for area i adjusted
for random variation. If Ei is big then exp(vi) becomes close to the simple
index θi, but if Ei is small then exp(vi) will approach to 1.
The variance component σ2 is an overall estimate of the regional variation. In tabel 6a-d the development of this component is seen during
the four time-periods, both for simple cholecystectomy and for all bile
tract operations. As seen from the tables, there is a trend towards less variation in the middle of the period followed by an increase in the latest
periods.
242
TABLE 6.a
Simple cholecystectomy women 20-79. Variance components (σ2) in random effect model in
the four sub-periods.
Period
Variance component σ2
1978-1983
1984-1987
1988-1991
1992-1995
0.027
0.020
0.026
0.045
TABLE 6.b
Simple cholecystectomy men 20-79. Variance components (σ2) in random effect model in the
four sub-periods.
Period
Variance component σ2
1978-1983
1984-1987
1988-1991
1992-1995
0.044
0.017
0.029
0.035
TABLE 6.c
All biliary tract procedures, women 20-79. Variance components (σ2) in random effect model
in the four sub-periods.
Period
Variance component σ2
1978-1983
1984-1987
1988-1991
1992-1995
0.020
0.014
0.021
0.027
TABLE 6.d
All biliary tract procedures, men 20-79. Variance components (σ2) in random effect model in
the four sub-periods.
Period
Variance component σ2
1978-1983
1984-1987
1988-1991
1992-1995
0.034
0.019
0.039
0.031
Table 7 shows an example of the effect of using a random effect model
instead of simple standardisation. The table shows the calculated index
values for simple cholecystectomy for men from 1978-83 in selected
areas.
243
TABLE 7
Estimated operation index for simple cholecystectomy for men, 1978-83. Estimates with and
without random effect.
Area code
With random effect
Without random effect
No. of op.
Population
Index
95%
conf. Lim.
Index
95%
conf. Lim
5503
0.71
(0.53-0.97)
0.42
(0.23-0.76)
11
55211
3002
0.71
(0.58-0.89)
0.63
(0.48-0.82)
53
180315
8007
1.00
(0.73-1.38)
1.00
(0,60-1.66)
15
29978
8001
1.00
(0.88-1.14)
1.00
(0.88-1.15)
209
450917
1309
1.16
(1.07-1.25)
1.17
(1.08-1.26)
597
1047560
3505
1.18
(0.93-1.51)
1.29
(0.97-1.72)
46
66970
The table illustrates the difference between the two estimates. Using the
‘random’ effect model, the same estimates are obtained for areas 5503 and
3002, while there is a big difference in the ‘raw’ SMR value. Area 5503 is
‘smoothed in’ towards the middle because the population base in area
3002 is more than 3 times greater than in area 5503. If you compare areas 8007 and 8001 they both have a ‘raw’ SMR value of 1, which they retain in the ‘random’ effect model. The change lies in the confidence intervals. Area 8001’s interval is retained because of the area’s large population, while area 8007 is narrowed when the ‘random’ effect model is used.
Area 1309 (the municipality of Copenhagen) has the largest population,
so there is (almost) no change between the two models’ estimates. Area
3505 shows that for ‘raw’ SMR-values, the ‘smoothing out’ moves towards 1 and that, compared with area 1309, it is dependent on the size of
the population.
The maps in this report (section 4 and 5.1.2) only use the “conservative” estimates from the random effect model.
A NALYSES OF 30- DAY MORTALITY RATES
Developments in 30-day mortality rates were analysed using two different
models.
First, developments in 30-day mortality for different operation groups
were analysed by a logistic regression. The analysis used the following independent variables: gender, age on admission, the index operation’s
method of admission (elective versus acute), acute or no cholecystitis at
the time of index operation, number of diagnoses during the index operation and period. The dependent variable is death within 30 days of
admission for the index operation.
244
The model was chosen by defining a base model that included the variables listed above. The possible interaction points between the base models’ variables were then found by means of a likelihood ratio test. Wherever an interaction occurs, the results are presented by means of a stratification.
Thirty-day mortality was then analysed by means of a Poisson regression to illustrate developments during the individual year controlled for
age, method of admission, cholecystitis and gender. The number of operations leading to mortality within 30-days is the dependent variable and the
number of operations in the defined strata is offset so that the analysis
refers to the proportion of cases with fatal consequences. The number of
diagnoses is not included in this analysis, since the available data material
is smaller when single years are introduced as a parameter.
Analysis of the importance of the hospital for 30-day mortality rates
Over the four sub-periods, the hospitals that performed the index operation were divided into four quartiles (for each period). On the basis of this
classification, the following cut points were defined regarding the number
of operations, so that for first period, hospitals that conducted <=84 operations were placed in the first quartile. Hospitals that performed more
than 84, but less than 155, were placed in second quartile etc.
TABLE 8
The number of operations which define quartiles for each period.
Periods
Number of hospitals
Cutpoints for number of operations
1978-1983
88
84-155-294
1984-1987
84
55-106-192
1988-1991
78
55-121-164
1992-1995
65
110-164-256
The analysis that included hospitals as independent variable was only
performed for simple cholecystectomy in a logistic regression that also included the other variables described.
ANALYSES OF COMPLICATED COURSES OF TREATMENT IN CASES OF SIMPLE CHOLECYSTECTOMY
The proportion of hospitalisations after which the patient is readmitted to
hospital for new treatment on biliary tracts within one year of an operation was analysed by logistic regression using the same independent variables used in the analysis of 30-day mortality. The analysis was only performed for simple cholecystectomy.
245
T HE DISTRIBUTION OF MUNICIPALITIES BETWEEN ADMISSIONS AREAS
TABLE 9
The distribution of municipalities between hospital areas in the period 1978-1983
Hospital area
1309
1401
1501
1502
1503
1516
2001
2003
2005
2006
2501
2502
3001
3002
3003
3004
3006
3501
3502
3503
3504
3505
3506
4001
4201
4202
4203
4204
4206
4207
4208
4209
4210
5001
5002
5003
5004
5501
5502
5503
5504
5505
6002
6003
6004
6006
6007
6008
6501
6502
6503
6504
6505
7002
7004
7005
7006
7008
7009
7011
7012
7601
7602
7603
7604
7605
8001
8003
8004
8005
8006
8007
8008
8009
8014
246
Municipality Municipality Municipality Municipality Municipality Municipality Municipality Municipality Municipality Municipality
1
2
3
4
5
6
7
8
9
10
101
147
157
173
181
153
161
165
167
169
183
187
155
185
151
159
163
171
175
189
201
205
207
208
213
215
219
221
231
233
223
227
209
211
225
229
235
237
217
251
253
255
257
261
263
265
259
267
269
271
305
315
321
337
339
341
345
303
307
311
319
325
331
333
301
309
317
323
313
329
335
327
343
353
357
373
377
393
397
369
371
375
387
391
395
351
385
389
355
363
383
359
367
379
381
361
365
401
403
405
407
409
411
427
435
477
479
439
441
447
461
471
483
485
491
497
449
489
495
425
431
437
473
429
445
451
499
475
481
487
443
493
423
421
433
501
507
513
523
533
535
537
509
511
515
525
527
543
505
517
521
531
539
541
503
519
529
545
557
561
563
571
553
555
573
551
565
567
577
559
569
601
625
627
607
611
653
609
615
619
575
621
623
629
603
605
613
617
631
651
661
671
675
677
679
683
657
663
681
685
655
669
659
667
665
673
705
711
743
749
703
713
733
751
709
717
723
729
731
747
715
737
745
727
741
707
721
725
739
735
701
775
789
791
793
763
777
779
781
783
765
785
787
773
761
767
769
771
803
817
831
835
837
843
845
849
851
819
821
829
839
847
719
801
815
823
833
809
827
861
805
807
813
825
811
841
TABLE 10
The distribution of municipalities between hospital areas in the period 1984-1987
Hospital area
1309
1401
1501
1502
1503
1516
2001
2003
2005
2006
2501
2502
3001
3002
3003
3004
3006
3501
3502
3503
3504
3505
3506
4001
4201
4202
4203
4204
4206
4207
4208
4209
4210
5001
5002
5003
5004
5501
5502
5503
5504
5505
6002
6003
6004
6006
6007
6008
6501
6502
6503
6504
6505
7002
7003
7005
7006
7008
7009
7012
7601
7602
7603
7604
7605
8001
8003
8004
8005
8006
8007
8008
8009
8013
8014
Municipality Municipality Municipality Municipality Municipality Municipality Municipality Municipality Municipality
1
2
3
4
5
6
7
8
9
101
167
147
157
173
181
153
161
165
169
183
187
155
185
151
159
163
171
175
189
201
207
211
213
215
219
221
231
233
205
208
223
227
209
225
229
235
237
217
251
253
255
257
261
263
265
267
269
259
271
305
315
321
339
341
345
303
307
311
319
325
331
333
337
301
309
317
323
313
329
335
327
343
353
357
373
377
393
397
369
371
375
387
391
395
351
385
389
355
363
383
359
367
379
381
361
365
401
403
405
407
409
427
435
477
479
447
461
471
483
485
491
497
439
441
449
489
495
425
431
433
437
473
429
445
451
499
475
481
487
443
493
423
421
501
507
513
523
533
535
537
509
511
515
525
527
543
505
517
521
531
539
541
503
519
529
545
557
561
563
571
553
555
567
573
551
565
577
559
569
575
601
627
607
611
609
615
621
623
629
603
605
613
617
619
625
631
651
661
671
675
677
679
683
653
657
663
681
685
655
669
659
667
665
673
705
711
737
743
749
703
713
733
751
709
717
723
729
731
735
747
715
745
727
741
707
721
725
739
701
775
789
791
793
763
777
779
781
783
765
785
787
773
761
767
769
771
817
831
835
837
845
849
851
819
821
829
839
847
719
801
815
823
833
809
827
861
805
807
813
825
803
811
843
841
247
TABLE 11
The distribution of municipalities between hospital areas in the period 1988-1991
Hospital area
1309
1401
1501
1502
1503
1516
2001
2003
2005
2006
2501
2502
3001
3002
3003
3004
3006
3501
3502
3503
3505
3506
4001
4201
4202
4203
4204
4206
4208
5001
5002
5003
5004
5501
5503
5504
6002
6003
6004
6006
6007
6008
6501
6502
6503
6504
6505
7002
7003
7005
7008
7009
7601
7602
7603
7604
7605
8001
8003
8004
8005
8006
8007
8008
8009
248
Municipality Municipality Municipality Municipality Municipality Municipality Municipality Municipality
1
2
3
4
5
6
7
8
101
167
147
157
173
181
153
161
165
169
183
187
155
185
151
159
163
171
175
189
201
207
208
213
215
219
231
205
223
227
209
211
221
225
229
233
235
237
217
251
255
257
261
263
265
253
259
267
269
271
305
315
321
337
339
345
303
307
311
319
325
331
333
301
309
317
323
341
313
329
335
327
343
353
357
361
373
377
393
397
369
371
375
387
391
395
351
385
389
355
359
363
367
379
381
383
365
401
403
405
407
409
427
435
473
475
477
479
481
487
447
461
471
485
491
497
439
441
449
489
495
425
431
433
437
421
423
429
445
451
483
499
443
493
501
503
507
513
523
533
535
537
509
511
515
527
543
505
517
521
531
539
541
519
525
529
545
553
555
557
559
561
563
569
571
573
551
565
567
575
577
601
625
627
607
611
609
615
619
621
623
629
603
605
613
617
631
651
661
671
679
683
653
657
663
677
681
685
655
669
659
667
665
673
675
705
711
737
743
749
703
713
733
751
709
717
723
729
731
735
747
715
727
741
745
701
707
721
725
739
769
775
789
791
793
763
777
779
781
783
765
785
787
773
761
767
771
803
831
835
837
843
845
849
851
819
821
829
839
719
801
815
823
833
809
827
861
805
807
817
813
825
841
847
811
TABEL 12
The distribution of municipalities between hospital areas in the period 1992-1995
Hospital area
1330
1401
1501
1502
1503
1516
2001
2005
2012
2501
2502
3001
3002
3003
3004
3501
3502
3503
4001
4201
4202
4203
4204
4206
5001
5002
5003
5004
5501
5504
6003
6006
6007
6008
6501
6502
6505
7002
7003
7005
7008
7009
7601
7602
7603
7604
7605
8001
8003
8004
8005
8007
8008
Municip. Municip. Municip. Municip. Municip. Municip. Municip. Municip. Municip. Municip. Municip. Municip. Municip.
1
2
3
4
5
6
7
8
9
10
11
12
13
101
167
147
157
173
181
153
161
165
169
183
187
155
185
151
159
163
171
175
189
201
207
208
213
215
219
231
209
211
221
225
229
233
235
237
205
217
223
227
251
253
255
257
261
263
265
259
267
269
271
305
315
321
327
339
343
345
303
307
325
331
301
309
311
317
319
323
333
341
313
329
335
337
351
353
357
361
365
373
377
385
393
397
355
359
363
367
369
371
375
379
381
383
387
391
395
389
401
403
405
407
409
427
435
443
475
479
481
487
447
461
471
485
497
439
441
449
477
489
495
421
425
431
433
437
473
493
423
429
445
451
483
491
499
501
507
513
523
533
535
537
509
511
515
525
527
543
505
517
521
531
541
503
519
529
539
545
553
555
557
561
563
567
569
571
573
551
559
565
577
603
607
601
609
615
619
625
575
605
621
623
629
611
613
617
627
631
651
661
671
675
679
683
653
655
657
659
663
667
669
677
681
685
665
673
705
711
737
743
749
703
713
715
721
725
739
741
751
709
717
719
723
729
731
733
735
747
727
745
701
707
761
769
775
789
791
793
763
777
779
781
783
765
785
787
773
767
771
803
811
817
831
837
843
845
849
851
805
819
821
829
835
839
801
815
823
833
809
827
861
807
813
825
841
847
249
Appendix 5.
Economical analyses
C OSTS OF GALLSTONE TREATMENT IN D ENMARK
The calculated cost of treating patients with gallstones includes the majority of expenses as amounts spent on technological equipment, theatre
staff and days spent in hospital are included. Estimates of the indirect
costs associated with convalescence are also included.
Costs of technological equipment
Laparoscopic equipment
The substantial difference in the direct cost of different biliary tract interventions is due to the equipment. Laparoscopic equipment consists of insufflation equipment for inserting CO2, video equipment (camera, recorder
and monitor) as well as the laparoscopic instruments (trochars, forceps,
etc.) which are available in one-off and reusable form. In the models, the
investment cost per laparoscopic column was set at DKK 440,000. (Bispebjerg Hospital). With a life span of five years and an interest rate of 5%,
this gave a depreciation of DKK 101,629 p.a. If 47 operations are performed per annum (an average number of laparoscopic cholecystectomies
for the country’s surgical departments), that gives a unit cost of DKK
2,162. On top of that there is also the surgical equipment, which for disposable instruments was set at DKK 5,561, and for reusable equipment at
DKK 834 per operation327. In this breakdown, the starting point was
the aforementioned price for reusable equipment, but in the sensitivity
analysis in the economical models a number of different prices were used
because a different number of operations and various discount schemes for
disposable equipment give different unit costs. The calculations were based
on the assumption that laparoscopic cholecystectomies made up 25% of all
simple cholecystectomies in 1991 and 75% in the subsequent years.
ERCP
The purchase price of ERCP equipment was set at DKK 520,000. With a
life span of five years and an interest rate of 5%, this gave an annual depreciation of DKK 120,107. Divided up between 300 interventions (diag-
250
nostic and therapeutic) per annum, this gave a unit cost of DKK 400. Since
the equipment is relatively sensitive, it often requires repair. Repair costs
were set at DKK 423 per use (based on average calculations over the period 1992-97, Bispebjerg Hospital). In the case of diagnostic ERCP, the
cost of utensils was set at DKK 100. In case of a therapeutic ERCP the cost
was set at DKK 1,500. Thus, the unit cost for equipment for diagnostic
ERCP was DKK 923, while the corresponding price for therapeutic ERCP
was DKK 2,323.
Theatre staff costs
Some operations take longer than others and the composition of the operating team depends on the nature of the operation. Thus, the staff costs
for the different gallstone interventions consist of an average hourly wage
(table 1) and the time spent on the operation by the different staff categories.
TABLE 1
Hourly wages per staff category
Staff category
a
Annual income
Hourly waged
a
Chief surgeon
543,231
319.08
Theatre nurse
Consultantb
450,516
264.62
Assistant nurse
Anaesthetistc
450,516
264.62
Senior registrar b
316,171
Registrarb
274,393
a:
b:
c:
d:
Annual income Hourly waged
Staff category
246,544
144.81
246,544
144.81
Anaesthetics nursea
246,544
144.81
185.71
Radiographera
214,925
126.24
161.17
Portera
206,169
121.10
a
The Government Wages and Conditions Statistics Office. Collective bargaining statistics, 1995
Collective bargaining agreements for doctors, pay scale 6 + supplement. The Danish Medical Association.
Considered equal to consultants.
Average hourly wage (in DKK) calculated of annual income (227 working days per annum á 7.5 hours).
The time spent on different gallstone related interventions (surgery and
ERCP) was calculated by sending a questionnaire survey to all surgical departments and selected medical gastroenterological departments. The response rates were 67% and 100%, respectively. The surgical departments
that did not reply were evenly distributed in terms of geography and type
of hospital. The responses formed the basis for the calculation of staff
costs for the different interventions (table 2 & 3). The departments were
not asked to do detailed time and motion studies, but only to provide an
assessment of time and staff resources.
251
TABLE 2
Staff involved in gallstone-related interventions. Average number of minutes
Laparoscopic cholecystectomy
Open cholecystectomyb
Other biliary tract surgery
80.59
74.33
124.38
Assistant a
77.06
72.41
125.00
Theatre nurse
30.68
33.06
53.53
Assistant nurse
133.13
124.14
176.87
Staff category
Surgeon
a
Anaesthesia nurse
140.45
130.19
176.38
Anaesthetist
131.68
121.85
172.96
Radiographer
11.90
18.00
17.50
Porter
18.74
18.91
20.00
a: Later calculations of unit prices were based on characteristics of the surgeon and the assistant, respectively. i.e. account was taken of
whether it was a department's consultants, senior registrar or registrar. Thus, the cost consists of a weighted average for the relevant
staff categories.
b: Including cholecystectomy by minilaparotomy
TABLE 3
Staff involved in gallstone-related interventions. Average number of minutes
Staff category
ERCP – Diagnostic
ERCP – Therapeutic
Endoscope operator
35.67
55.26
1st assistant
60.75
79.91
2nd assistant
43.46
57.74
3rd assistant
3.75
5.22
17.53
17.67
Porter
The endoscope operator corresponds to a chief surgeon/consultant; 1st and 2nd assistant to a nurse and 3rd assistant to a radiographer.
The average number of minutes decline for the 2nd and 3rd assistant as different departments use different numbers of assistants.
One question posed in the questionnaire was in how many of the operations the surgeon and assistant were consultants, senior registrars or
registrars. The departments were also asked to state how frequently intraoperative cholangiography was used. An expected price was then calculated on the basis of the hourly rates for the groups of doctors and the
probability that the surgeon can be ascribed to the different categories.
The estimated costs of different operations were calculated on the basis of
the hourly wages for the different staff groups.
When calculating staff costs for different operations (table 4), the average time spent by the different staff categories and the respective hourly
wages were used. Staff costs were also calculated for the departments with
the lowest and highest staff costs. Average costs were used in the financial
calculations, while minimum and maximum values were used in the sensitivity analyses.
252
TABLE 4
Staff costs at various interventions (in DKK).
Cholecystectomy
ERCP
Opena
Laparoscopy
Otherb
Average
1659.08
1744.76
2580.77
484.45
672.74
Maximum
3404.49
3021.37
4347.49
1597.41
2109.69
Minimum
586.39
773.17
1063.43
172.36
252.13
Diagnostic
Therapeutic
a: Including cholecystectomy by minilaparotomy
b: Other biliary tract surgery
Costs associated with hospitalisation
Ideally, when calculating the costs, bed price per day should reflect costs
associated with nursing, food, administration, etc. The economical models used the general rate for patients with a free choice of hospital, which
were fixed at DKK 2,255/day (1997 figures).
Average hospital day costs can conceal major variations in the individual treatment costs for the same indication and for bed days. Thus, a reduction in the time a patient is confined to bed will often mean a reduction in the number of least expensive bed days. It is also open to question
whether the general price for bed-days also reflect the cost of the actual
operation, which would mean some costs were registered twice. And
finally, a given bed-day price will not only reflect and relate to, for example, gallstone operations. It will also reflect the costs associated with the
days spent in bed after other operations in the same ward. In the economical models, hospital bed-day rates were varied by means of sensitivity analyses in order to identify these uncertainty factors.
Costs related to absence due to illness
The indirect costs include the loss production due to sick leave. These
include the patient (and his/her immediate family) devoting working
hours and spare time to convalescence. It is difficult to measure indirect
costs exactly, partly because of the difficulties involved in placing a value
on ‘productive activity’ in the home.
Few gallstone studies have calculated indirect costs. In a Swedish survey
[80], the indirect costs were estimated on the basis of the average hourly
wage in different businesses (industry, mining and quarrying) (SKr 139.13),
the gender-standardised average number of working hours per day (4.1
hour/day), the proportion of the population in the workforce (0.779) and
253
finally, the proportion of the workforce in work (0.915). The result was a
production loss per day of SKr 406.6 (139.19 x 4.1 x 0.779 x 0.915).
If these calculations were transferred to Denmark (based on 1994 figures), the indirect costs per sick day could be estimated based on the proportion of the population in the workforce at 0.5597, the proportion of
the workforce in employment at 0.89, the average hourly wage at DKK
125.60 and the average number of man hours per day at 4.76. In total,
this would give an average production loss of DKK 297.81 per day due to
illness. If the proportion of the population in workforce was put at 0.789
instead, the cost per day due to illness would be DKK 419.82. If no corrections were made for the size of the workforce and level of unemployment, then the cost per day due to illness would be DKK 597.86.
In principle, the so-called intangible costs such as pain, anxiety, etc.
should also be included in a socio-economic analysis. Estimates for these
elements have not been included in this report.
Comments
The costs included in these financial models were based on a number of
estimates which, in the nature of things, were subject to a number of uncertainty factors. Consequently, sensitivity analyses have been conducted
in the estimations of the specific models, which amongst other things varies
the cost estimates.
It seemed justifiable to omit expenses incurred during the preoperative
phase, since they were estimated at only 10% and 14% of total costs307 for
traditional open cholecystectomy and laparoscopic cholecystectomy,
respectively.
S ENSITIVITY ANALYSES OF THE ECONOMICAL MODELS
This section shows in schematic form, how the results of the financial
models were altered by adjustments in the individual parameter values.
The main conclusions are summed up in chapter 11 of the report.
254
TABLE 5
Cholecystectomy by laparoscopy, minilaparotomy and traditional open laparotomy.
Sensitivity analyses of the three alternatives. Variations in unit costs.
Parameter
New value
Average expected direct costs – DKK
Laparoscopy
Baseline values
Minilaparotomy
10,532
7,351
Trad. open lap
Marginal cost
effectiveness lap. vs. open
15,327
46,334
Bed-day price (2,255)
1,000
4,000
7,356
14,948
4,223
11,699
8,325
25,877
3,711
105,598
Staff costs
(laparoscopic cholecystectomy)
773
3,021
9,560
11,808
7,351
7,351
15,327
15,327
55,721
34,000
Staff costs (cholecystectomy by
minilaparotomy)
586
3,404
10,532
10,532
6,278
9,096
15,327
15,327
-
Staff costs (cholecystectomy
by trad. open lap.)
586
3,404
10,532
10,532
7,351
7,351
14,254
17,073
35,970
63,198
Unit price for the laparoscopic
equipment (the number of
operations per column)
0
500
1,000
3,000
8,369
8,869
9,369
11,369
7,351
7,351
7,351
7,351
15,327
15,327
15,327
15,327
67,226
62,395
57,564
38,241
Equipment for minilaparotomy
500
10,532
7,851
15,327
-
Indirect costs
100
500
11,563
15,687
8,373
12,461
18,128
29,330
63,430
131,811
TABLE 6
Cholecystectomy by laparoscopy, minilaparotomy and traditional open laparotomy.
Sensitivity analyses of the three alternatives. Variations in time spent in hospital.
Parameters
New value
Average expected direct costs (in DKK)
Laparoscopy
Baseline values
Minilaparotomy
Trad. Open lap.
10,532
7,351
15,327
Successful treatment
1 day
3 days
5 days
7 days
8,539
12,524
16,509
20,493
5,348
9,353
13,357
17,363
4,199
8,650
13,101
17,553
Complication (re-operation)
8 days
10 daysa
12 days
10,486
10,532
10,577
7,306
7,351
7,396
15,282
15,327
15,372
Peripheral bile duct lesion
5 days
7 daysa
9 days
10,514
10,532
10,549
7,343
7,351
7,358
15,315
15,327
15,339
Central bile duct lesion
10 days
14 daysa
18 days
10,508
10,532
10,555
7,348
7,351
7,353
15,324
15,327
15,331
Conversion
4 days
6 daysa
8 days
10,081
10,532
10,983
6,900
7,351
7,802
15,327
15,327
Indirect costs
DKK 100
DKK 500
11,563
15,687
8,373
12,461
18,128
29,330
a: Baseline estimat
255
TABLE 7
Disposable vs. reusable instruments for laparoscopic cholecystectomy.
Sensitivity analyses of the alternatives. Variations in unit costs and time spent in hospital.
Parameters
New value
Instruments (in DKK)
Disposable
Baseline values
256
Reusable
Marg. cost
efficiency
12,407
8,485
Bed-day price
DKK 1,000
DKK 4,000
9,494
16,458
5,315
12,894
68,968
58,810
Disposable equipment
DKK 1,000
DKK 6,000
7,846
12,846
8,485
8,485
- 10,545
71,963
Reusable equipment
DKK 500
DKK 1,000
12,407
12,407
8,151
8,651
70,230
61,979
Hospitalisation if success
1 dag
3 days
10,674
14,141
7,247
9,724
56,562
72,875
Hospitalisation for post-operative
complications
3 days
7 days
12,353
12,462
8,263
8,708
67,487
61,950
Hospitalisation for conversion
4 days
8 days
12,121
12,694
8,094
8,877
66,460
62,977
Hospitalisation for central
bile duct lesion
10 days
18 days
12,384
12,431
8,462
8,509
64,719
64,719
Treatment of Gallstone patients
In the Danish health care system, more than DKK 100 million per year are
spent on treating patients with benign biliary tract diseases.
This report is the first attempt at performing a health technology
assessment of treatment of gallstone patients. By including the technology,
the patient, the organisation as well as the economy, a health technology
assessment is an analytical tool that serves as basis for ensuring an optimal
treatment of patients within the given economical framework.
The report is based on a systematic review of the literature and a
thorough analysis of data from The National Hospital Register where all
hospital admissions in Denmark are recorded. By reviewing the literature
using explicit criteria, the fundament for performing an objective assessment
of the various treatment modalities has been established. At the same time,
analyses of data from The National Hospital Register form a clear picture of
the development of treatment of gallstone patients throughout Denmark.
By combining the technology with the economical analyses, the limited
knowledge of patients’ preferences for the various treatment modalities
as well as the organisational aspects, the report questions a number of
well-established treatment modalities and the organisation of these.
It is the hope, that this report will form part of a knowledge-based
fundament for the development of a national strategy for prevention,
diagnosis and treatment of patients with biliary tract disease.
Torben Jørgensen
Treatment of
Gallstone
patients
A health technology assessment
Counselling and advising in connection with HTA projects is given by:
Danish Institute for Health Technology Assessment
National Board of Health
13, Amaliegade
PO. Box 2020
DK-1012 Copenhagen
Denmark
Phone: + 45 33 91 16 01
Fax: + 45 33 91 70 61
E-mail: [email protected]
Homepage: http://www.dihta.dk
Further copies of this publication can be bought at:
Sundhedsstyrelsens Publikationer
c/o Schultz Information
12, Herstedvang
DK-2620 Albertslund
Denmark
Phone: + 45 70 26 26 36
Fax: + 45 43 63 62 45
NIPH & Danish Institute for Health Technology Assessment 2000
National Institute of Public Health
25, Svanemøllevej
DK-2100 Copenhagen , Denmark
Phone: +45 39 20 77 77
Fax: +45 39 20 80 10
E-mail: [email protected]
Homepage : www.dike.dk
Danish Institute for
Health Technology Assessment
D I T H A