Gastroenterol Clin N Am
32 (2003) 1145–1168
Diagnosis and management of
cholecystitis and cholangitis
Ian F. Yusoﬀ, MBBSa, Jeﬀrey S. Barkun, MD, MScb,
Alan N. Barkun, MD, MScc,*
a
McGill University Health Centre, 1650 Cedar Avenue, Montreal, Quebec H3G 1A4, Canada
b
Department of Surgery, Royal Victoria Hospital, McGill University Health Centre,
Montreal, Quebec, Canada H4Y 1S1
c
Division of Gastroenterology, McGill University Health Centre, Montreal General Hospital,
Room D7.148, 1650 Cedar Avenue, Montreal, Quebec H3G 1A4, Canada
The main biliary tract emergencies are acute cholecystitis, ascending
cholangitis, and acute pancreatitis. These conditions usually arise as
a consequence of calculi obstructing the biliary tree or gallbladder. Less
frequently they may result from benign or malignant strictures of the biliary
tree, biliary tree manipulation, or biliary sludge [1]. Despite therapeutic
advances these conditions still cause signiﬁcant morbidity and mortality,
particularly in the elderly [2]. This article reviews acute cholecystitis and
cholangitis with a focus on the clinical presentation, diagnosis, and state-ofthe-art management. Acute pancreatitis is dealt with elsewhere in this issue.
Acute calculous cholecystitis (ACC)
Acute cholecystitis is an acute inﬂammation of the gallbladder. Gallstones are present in over 90% of cases, and cause persistent obstruction of
the gallbladder outlet because of impaction in the neck of the gallbladder,
Hartmann’s pouch, or cystic duct [2,3]. In the remaining 5% to 10% of
cases, gallstones are not identiﬁed, so-called ‘‘acalculous cholecystitis’’ [4].
Dr. Yusoﬀ is an Amy and Athelstan Saw Fellow of the Faculty of Medicine and
Dentistry, The University of Western Australia.
Dr. Alan Barkun is a (Chercheur Clinicien Boursier) Senior Research Scholar of the
Fonds de la Recherche en Sante´ du Que´bec.
* Corresponding author.
E-mail address: [email protected] (A.N. Barkun).
0889-8553/03/$ - see front matter Ó 2003 Elsevier Inc. All rights reserved.
doi:10.1016/S0889-8553(03)00090-6
1146
I.F. Yusoﬀ et al / Gastroenterol Clin N Am 32 (2003) 1145–1168
Natural history and prevalence of cholelithiasis and cholecystitis
Gallstones are ubiquitous; however, because most patients are asymptomatic, their precise incidence is uncertain. It is estimated that 10% to 15%
of the United States adult population have gallstones [5], and studies from
other westernized societies describe a prevalence of 5% to 20% [6–8]. Only
a minority of patients with gallstones become symptomatic or develops
cholecystitis [9]. The GREPCO investigators estimated the cumulative
probability of developing a complication in patients with asymptomatic
cholelithiasis after 10 years of follow-up was 3% [10] and other studies have
conﬁrmed a low rate of 0.5% to 3% per year of developing complications
[9,11–13]. Once the patient is symptomatic, the rate of biliary complications
rises [9,10,12,13]. The natural history may be less benign in selected
subgroups, such as diabetics and organ transplant recipients [14]. Because
the epidemiology and natural history of gallstones is diﬀerent in Asian
populations, this discussion is largely limited to Westernized societies [6].
Pathophysiology
The initial event in ACC is believed to be obstruction to gallbladder
drainage [3]. This causes an increase in intraluminal pressure, gallbladder
distention, and wall edema that may progress to venous and lymphatic
obstruction, ischemia, and necrosis. A number of potential mediators have
been identiﬁed including cholesterol-supersaturated bile, lysolecithin,
phospholipase A, and prostaglandins [2,3,6]. Enhanced production of
prostaglandins is believed to play a key role in mediating inﬂammation, and
agents that reduce prostaglandin production have been shown to block the
inﬂammatory response and reduce the pain of cholecystitis [15,16]. Bile is
sterile in the early stages of acute cholecystitis and infection is believed to be
a secondary event [17,18]. Indeed, although ACC is often considered an
infection, bile cultures are positive only in 20% to 75% of patients [17–19].
The organisms most commonly cultured are enteric bacteria including
Escherichia coli, Klebsiella, and Enterococcus [17–19].
Clinical presentation
Patients with ACC usually present with abdominal pain associated with
fever, nausea, and vomiting. Pain and tenderness are usually localized to the
right upper quadrant and the pain may radiate to the back, right scapula, or
right clavicular area [2,20]. Three quarters of patients with ACC report
a previous attack of biliary colic [21]. The pain is distinguished from biliary
colic by its prolonged duration and the presence of Murphy’s sign (where
mid inspiration is inhibited by pain on palpation of the right upper
quadrant). Singer et al [22] found that a positive Murphy’s sign was highly
sensitive (97%) and predictive (positive predictive value 93%) of ACC.
I.F. Yusoﬀ et al / Gastroenterol Clin N Am 32 (2003) 1145–1168
1147
Presentation in elderly patients may be atypical. Haﬁf et al [23] reported that
among 131 patients over 70 years with ACC, right upper quadrant pain was
absent in 27% and fever was absent in 45% [23].
Diagnosis
The combination of prolonged, constant right upper quadrant pain and
tenderness with fever are highly suggestive of ACC. A leukocytosis with
increased neutrophils and band forms is usually present. There may be mild
elevation of the transaminases or bilirubin. A signiﬁcantly elevated bilirubin
should raise the possibility of choledocholithiasis or Mirrizzi syndrome
(obstruction of the common hepatic duct by a calculus impacted in
Hartmann’s pouch) (Fig. 1) [3,24]. The diagnosis can usually be made by
either ultrasound scanning or biliary scintigraphy. Ultrasonography is
highly sensitive and speciﬁc for the presence of gallstones greater than 2 mm,
but does not always conﬁrm the diagnosis of ACC [6,25]. The sonographic
features of ACC include gallbladder wall thickening, pericholecystic ﬂuid,
Fig. 1. Mirrizzi syndrome. Cholangiography showing stone in the gallbladder infundibulum
(solid arrow) compressing externally the proximal common bile duct (open arrow) with resulting
proximal intrahepatic bile duct dilatation.
1148
I.F. Yusoﬀ et al / Gastroenterol Clin N Am 32 (2003) 1145–1168
gallbladder distention, and a sonographic Murphy’s sign (Fig. 2) [25–27].
The reported test performance of ultrasound varies with sensitivities of 48%
to 100% and speciﬁcities of 64% to 100%; the presence of multiple criteria
increases its diagnostic accuracy [26–32]. Biliary scintigraphy is highly
accurate and is the gold standard for the diagnosis of cystic duct
obstruction. Multiple studies have conﬁrmed that scintigraphy has
a sensitivity and speciﬁcity for the diagnosis of ACC of over 94% [31–36].
Scintigraphy, however, displays reduced speciﬁcity in the presence of hepatic
impairment, parenteral nutrition, or when the patient is in the fasting state
[2]. A positive scan may also be seen in chronic cholecystitis [6]. Scintigraphy
gives little information about nonobstructing cholelithiasis and cannot
detect other pathologic states. In a rigorous meta-analysis, Shea et al [37]
reported that scintigraphy was more sensitive and speciﬁc than ultrasonography in ACC, and recommended it be the preferred test in patients with
otherwise equivocal signs of ACC. Nonetheless, the choice of initial imaging
modality remains controversial and varies with institution. The authors’
practice is to use ultrasonography as the screening test for ACC given its
Fig. 2. Cholecystitis. Ultrasonographic study of the gallbladder showing a thickened
gallbladder wall (solid arrows) and pericholecystic ﬂuid (open arrow). Gallstones are seen in
the gallbladder (S ) with the characteristic acoustic shadowing (right brace).
I.F. Yusoﬀ et al / Gastroenterol Clin N Am 32 (2003) 1145–1168
1149
relatively high accuracy, availability, portability, low cost, quickness, and
ability to detect other pathology. Scintigraphy is usually reserved for cases
where the ultrasound is normal and the clinical suspicion remains high.
Magnetic resonance imaging (MRI) (Fig. 3) and computed tomography
(CT) as an adjunct to ultrasound have been reported as being useful in the
diagnosis of ACC but scanning an acutely ill patient may be diﬃcult and the
added time and expense are infrequently justiﬁed [30,38].
Management
The immediate management of ACC includes having the patient fast;
ﬂuid and electrolyte resuscitation; and parental (narcotic) analgesia. If the
patient is vomiting, or if there is evidence of an ileus or gastric distention,
nasogastric tube placement is appropriate [1]. Indomethacin has been
reported to reverse the inﬂammatory changes in ACC and improve
gallbladder contractility when given early, and diclofenac has been reported
to reduce the rate of progression to ACC in patients with symptomatic
Fig. 3. Cholecystitis. MRI study (heavily T2-weighted) showing a thickened gallbladder wall
(A, solid arrows), sloughed mucosa in the gallbladder lumen (A, open arrow), as well as
pericholecystic ﬂuid (B, open arrow).
1150
I.F. Yusoﬀ et al / Gastroenterol Clin N Am 32 (2003) 1145–1168
gallstones; however, neither of these agents is used widely for this purpose
[15,16,39]. Intravenous antibiotics are usually commenced empirically when
there are systemic signs (eg, high fever, tachycardia, and hypotension) or if
there has been no improvement over 12 hours with conservative
management [3]. The favorable results of antibiotic treatment that reduces
septic complications seems to depend more on adequate serum rather than
tissue concentrations [30]. The choice of antibiotic varies with local
experience and patterns of bacterial resistance. Single-agent therapy with
an extended spectrum cephalosporin provides safe, appropriate coverage in
most cases; however, in severe or high-risk cases, anaerobe cover is required
(ie, by adding a nitroimidazole) [41,42]. In patients undergoing early
uncomplicated cholecystectomy, prolonging the antibiotic course for more
than 1 day postoperatively has not shown to be of beneﬁt [43]. It must be
emphasized that the optimal therapy in ACC is surgery, not antibiotic
therapy.
Cholecystectomy
Surgical cholecystectomy has been the treatment of choice for ACC since
Langenbuch ﬁrst described it in 1882. Key issues regard the timing and the
type of surgery and the treatment of those unﬁt for surgery. Approximately
20% of patients with ACC require emergency surgery because of clinical
deterioration or other features of complicated disease, such as peritonitis or
perforation [2,3]. If the nature of the symptoms is uncertain, exploratory
surgery may be indicated [6]. For the remaining patients, early surgery has
been shown to be superior to delayed surgery. Six randomized controlled
trials before and after the advent of laparoscopic cholecystectomy (LC) have
compared early surgery (within days of admission) with delayed surgery
(performed 6 to 8 weeks after the event) [4–49]. These studies have found
that mortality and complication rates of early cholecystectomy are no
diﬀerent than for delayed surgery, and that early surgery is preferable
because of reduced total hospitalization costs and morbidity because
approximately 10% to 25% of patients are admitted with recurrent
complications of gallstone disease.
Laparoscopic cholecystectomy has changed the approach to biliary
disease in the last two decades and it has been become the procedure of
choice for elective cholecystectomy. Three randomized controlled trials
[48–50] and multiple nonrandomized trials [51–56] studied the use of LC in
ACC. These trials conﬁrm that early LC is a safe and feasible option
in ACC. Furthermore, these trials suggest LC within 48 to 72 hours of
presentation (early surgery) is preferable to surgery after 3 to 5 days of
conservative therapy (interval surgery) and surgery delayed 6 to 12 weeks
after the attack (delayed surgery). The main reason for this conclusion is
reduced conversion rates in the early surgery group when compared with
the interval surgery group and reduced hospital stay in the early surgery
I.F. Yusoﬀ et al / Gastroenterol Clin N Am 32 (2003) 1145–1168
1151
group. Indeed, early in the course of ACC inﬂammation and ﬁbrosis are
limited and tissues planes are easier to ﬁnd, facilitating laparoscopic
dissection. There may, however, be an increased risk of gallstone spillage
with LC and this may increase the potential risk of subsequent abscess
formation [57].
Percutaneous cholecystostomy
In high-risk patients, where the risks of surgery may outweigh the
beneﬁts, percutaneous cholecystostomy has been reported as an acceptable
option with technical success in most series of over 90% [58–64]. This
procedure can be performed at the bedside under ultrasound control and
gives clinical improvement in 75% to 90% of patients with reported
mortality rates of 5% to 20% (usually related to underlying condition)
[58,59,63,64]. An incomplete or poor response after 48 hours should prompt
a search for alternate sources of sepsis, complications, or tube dislodgment
[3]. Once the patient has recovered, elective cholecystectomy should be
performed [65]. An attempt at elective LC is reasonable in this setting
[64,66,67]. Alternatively, if the patient remains unﬁt for surgery, percutaneous extraction of the calculi subsequently can be performed under
radiologic or cholecystoscopic guidance [62,68,69]. In selected cases
gallstone dissolution (with methyl tert-butyl ether) and disruption (with
extracorporeal lithotripsy) have been reported [70,71].
Outcomes and complications of ACC
The reported mortality rate of ACC treated with LC is less than 0.5%
with reported morbidity rates of 5% to 20% [48,49,52–55,72–75]. A number
of complications of ACC may occur including gallbladder perforation,
gallbladder gangrene, emphysematous cholecystitis, and empyema. The
presence of any of these calls for urgent surgery. Risk factors for
complications include advanced age; male gender; and associated diseases,
such as diabetes, high temperature, and signiﬁcant leukocytosis [76].
Gangrenous cholecystitis occurs in 2% to 30% of cases of ACC [3,76].
Perforation of the gallbladder is present in 3% to 10% of patients with ACC
[2]; the most common form of perforation is subacute, with walling oﬀ of the
process as a pericholecystic abscess [77]. Free perforation is less common;
occurring usually in institutionalized patients, it presents with general
peritonitis, and has a high mortality rate [77]. Emphysematous cholecystitis
is an uncommon condition occurring when there is secondary infection of
the gallbladder wall with gas-forming organisms. It is most common in
elderly, diabetic men and it is treated with immediate administration of
antibiotics (directed at anaerobes, coliforms, and clostridia species) and
urgent surgery because of the high incidence of free perforation [6]. A
clinical algorithm for the management of ACC is presented in Fig. 4.
1152
I.F. Yusoﬀ et al / Gastroenterol Clin N Am 32 (2003) 1145–1168
Fig. 4. Clinical algorithm for the management of ACC.
Acute acalculous cholecystitis
Acute acalculous cholecystitis (AAC) is an acute inﬂammation of the
gallbladder in the absence of demonstrable cholelithiasis [78]. It has been
suggested that a more appropriate name is ‘‘necrotizing cholecystitis’’ to
distinguish it as a distinct entity [79]. AAC accounts for 2% to 12% of
all cases of cholecystitis, and in the United States 5% to 10% of
cholecystectomies are performed for AAC [4,78,80]. AAC most frequently
occurs in those who are critically ill from trauma, sepsis, or burns [4,78,80].
Compared with ACC, AAC tends to have a more complicated course and
a higher morbidity and mortality [80]. Reported mortality rates range from
10% to 50%, in part because of the severity of the underlying disease
[78,80]. Other reported risk factors include vascular disease, male gender,
systemic vasculitides, HIV infection, diabetes mellitus, acute renal failure,
immunosuppression, prolonged fasting, and total parenteral nutrition
[78,80–82]. It has also been reported in patients without identiﬁable risk
factors [83,84].
Pathophysiology
The pathogenesis of AAC is likely multifactorial with gallbladder stasis,
paresis, and ischemia possibly playing a role [1,78]. Most patients with this
condition have fasted for prolonged periods, are immobile, and often have
I.F. Yusoﬀ et al / Gastroenterol Clin N Am 32 (2003) 1145–1168
1153
experienced hemodynamic instability, and over 70% may have associated
atherosclerotic disease [82]. It is postulated that concentrated, stagnant bile
and reduced gallbladder perfusion lead to a chemical and ischemic injury to
the gallbladder epithelium [78]. Cholecystectomy specimens from patients
with AAC (but not ACC) demonstrate impaired gallbladder microcirculation suggesting that splanchnic vasoconstriction or intravascular coagulation may be important events [85,86]. As in ACC, infection is thought to be
a secondary event [17].
Clinical presentation and diagnosis
The clinical features of AAC may be the same as ACC; however, some or
all of these features may be absent [87]. Indeed, pyrexia may be the only
symptom, and up to 75% of cases may initially not have symptoms
referable to the right upper quadrant [78]. Diagnostic tests used are those
outlined for ACC. Ultrasound is usually the ﬁrst line of investigation
because it is widely available, can be performed at the bedside, and can
detect concomitant lesions [3,87]. The sonographic features are similar to
those of ACC, but without calculi [87,88]. Reports of ultrasound sensitivity
have varied from 29% to 92% with speciﬁcity being over 90% [80,88,89].
CT is often performed because it is superior to sonography in detecting
other intra-abdominal pathology [90]. The role of hepatobiliary scintigraphy in AAC is debated [78]. It is highly sensitive in diagnosing AAC;
however, it may lack speciﬁcity because fasting for prolonged periods may
result in thick, viscous bile and a false-positive scan [4,91]. Morphineaugmented scintigraphy may overcome this shortcoming, and it may
complement sonography in cases where the diagnosis is uncertain [80,89]. In
practice multiple studies may be necessary before the diagnosis becomes
apparent [80,89].
Treatment
Initial supportive management is similar to ACC. Thereafter the
management depends on the patient’s condition. In patients ﬁt for surgery,
open cholecystectomy (OC) has been the traditional approach [2,3,80]. LC
has also been reported as an acceptable alternative in the early stages of
AAC [2,92]. In critically ill patients, cholecystostomy is often preferred.
Percutaneous cholecystostomy has been reported in a number of uncontrolled trials with favorable success rates [93,94]. The catheter may be
left in place for 6 to 8 weeks and if no gallbladder stones are present at
postdrainage cholangiography, the catheter is removed and cholecystectomy
is usually unnecessary. Endoscopic transpapillary gallbladder drainage has
been described for AAC but this technique has few advantages and several
potential disadvantages (including cost and need for sedation) compared
with percutaneous cholecystostomy [95].
1154
I.F. Yusoﬀ et al / Gastroenterol Clin N Am 32 (2003) 1145–1168
Acute cholangitis
Acute cholangitis occurs as a result of bacterial infection superimposed
on obstruction of the biliary tree. Of the common complications of
gallstones, cholangitis is the most rapidly lethal entity, making accurate
diagnosis and early treatment imperative [6]. Patients who fail conservative
therapy and do not have appropriate drainage have mortality rates
approaching 100% [96–98].
Pathophysiology and etiology
Bile is normally sterile [99]. The sphincter of Oddi, bile ﬂow, and
bacteriostatic properties of bile help maintain this sterility [100]. It is
believed that biliary obstruction reduces antibacterial defenses, causes a state
of immune dysfunction, and increases small bowel bacterial colonization
[98]. Bacteria are able to gain access to the biliary tree; however, the precise
route of infection is uncertain. Ascent from the duodenum or seeding
through the portal vein are the most likely sources, but other possibilities
include spread through the lymphatics or hepatic secretion [98,101]. Once
obstructed bile is colonized, stasis allows for enhanced bacterial multiplication, whereas increased ductal pressure facilitates spread into the
lymphatics and bloodstream [98].
Biliary obstruction is necessary but not suﬃcient to cause cholangitis [6].
Partial obstruction is associated with a higher rate of infection than complete
obstruction, and obstruction from calculi is associated with a much higher
rate of cholangitis than neoplastic obstruction (which is associated with
cholangitis in about 10% of cases) (Fig. 5) [98,101]. Biliary obstruction after
biliary intervention carries a very high risk of cholangitis [2]. The organisms
most commonly cultured in cholangitis are E coli, Enterococcus, Klebsiella,
Fig. 5. Impacted bile duct stone. Endoscopic image of a patient with acute cholangitis showing
an impacted stone in the ampulla of Vater before (A) and following endoscopic sphincterotomy
(B). (See also Color Plate 17.)
I.F. Yusoﬀ et al / Gastroenterol Clin N Am 32 (2003) 1145–1168
1155
and Enterobacter [98,102]. Pseudomonas, skin, and oral ﬂora may be found
after biliary interventions and anaerobes are found in up to 15%, most
commonly in elderly patients after biliary surgery [6,100,102]. The most
common cause of cholangitis in the United States is choledocholithiasis
secondary to cholelithiasis with common bile duct stones being found in up to
10% of patients who present with symptomatic gallstones [1,98]. Primary bile
duct stones are unusual in North America but are common in Hong Kong and
Southeast Asia where Oriental cholangiohepatitis is endemic [6]. Less
common causes of cholangitis include obstructing primary tumors of the
ampulla, bile ducts, or pancreas; metastatic tumors to the porta hepatis or
peripancreatic lymph nodes; benign strictures; and primary sclerosing
cholangitis. With increased biliary interventions, postprocedural cholangitis
is becoming more common [2]. Rare causes of cholangitis include obstruction
from hemobilia, parasites, and hereditary abnormalities of the biliary tree
[1,100].
Clinical presentation and diagnosis
Presentation of cholangitis is variable with the classic Charcot’s triad of
fever, right upper quadrant pain, and jaundice present in 50% to 70% of
patients [6,98,103,104]. Fever is usually present in 90% of cases, with jaundice
and abdominal pain present in approximately 60% and 70%, respectively
[98]. A small proportion of patients present with altered mental status (10%
to 20%) and hypotension (approximately 30%) (the so-called ‘‘Reynold’s
pentad’’ when present with Charcot’s triad) [6,98,103,104]. Right upper
quadrant tenderness is present in two thirds of patients but signs of peritoneal
irritation are less common [1]. Severe cholangitis may be associated with
hepatic microabscesses that usually carry a poor prognosis (Fig. 6).
Fig. 6. Hepatic abscesses. Patient with acute cholangitis and a cholangiogram that
demonstrates a multitude of small hepatic abscesses in continuity with the biliary tree.
1156
I.F. Yusoﬀ et al / Gastroenterol Clin N Am 32 (2003) 1145–1168
The diagnosis of acute cholangitis is often made clinically but laboratory
and imaging conﬁrmation is important to enable distinction from other
conditions, such as acute cholecystitis, hepatic abscesses, and pancreatitis.
Typically, laboratory investigations reveal leukocytosis, hyperbilirubinemia,
elevated alkaline phosphatase, and mild elevation of transaminases
[6,98,103]. Serum amylase may be elevated in up to 30% of patients [1].
Ultrasonography or CT scan are the most commonly used ﬁrst-line imaging
modalities. Ultrasound is highly sensitive for cholelithiasis [37] but less
sensitive (approximately 50%) for choledocholithiasis [105]. Choledocholithiasis may, however, be inferred if there is associated biliary dilation in
the presence of cholelithiasis. A normal ultrasound does not rule out
cholangitis [6]. Most studies suggest that CT is superior to ultrasonography
for determining the level of biliary obstruction [106–108]. MRI and MR
cholangiopancreatography are accurate for detecting choledocholithiasis
and determining biliary anatomy and speciﬁc features of cholangitis have
been described [109], but this test is probably of limited value in acute
cholangitis. Endoscopic retrograde cholangiopancreatography (ERCP) is
highly accurate for determining the cause of biliary obstruction and allows
appropriate intervention where required. Given its potential for complications and availability of accurate noninvasive imaging ERCP should not be
used solely as a diagnostic modality. Rather, it should be used when the
likelihood of intervention is high, as is often the case in patients with
clinically suspected cholangitis. Indeed, if cholangitis is suspected in
a patient with cholelithiasis and the likelihood of common bile duct stone
is high [100,110,111], the authors believe investigations should be limited (to
blood tests and transabdominal ultrasound) and early referral made for
ERCP.
Treatment
Initial management consists of correction of ﬂuid and electrolyte deﬁcits;
correction of coagulopathy (caused by vitamin K deﬁciency from prolonged
jaundice or low platelets from sepsis); and analgesia. In all cases of
suspected cholangitis, blood cultures should be obtained and empirical
antibiotics commenced. Although particular agents (eg, ﬂuoroquinolones)
have better biliary penetration, this has not been shown to be of primary
importance in aﬀecting outcome [98]. An aminoglycoside and ampicillin are
no longer the ideal regimen because of emerging gram-negative resistance
and concerns regarding nephrotoxicity [98,112]. Multiple newer regimens
have been shown to be eﬀective, including combination therapy with an
extended-spectrum cephalosporin, metronidazole, and ampicillin; singleagent or combination ﬂuoroquinolones; and ureidopenicillins alone or with
metronidazole [98,113–118]. The choice of agent needs to be guided by local
sensitivities, costs, and the need for anaerobic coverage (eg, in the elderly
and those with biliary manipulation). The authors’ practice is to use a single
I.F. Yusoﬀ et al / Gastroenterol Clin N Am 32 (2003) 1145–1168
1157
broad-spectrum agent, such as a ureidopenicillin (eg, ticarcillin and
clavulanic acid) where possible. All patients with ascending cholangitis
require biliary drainage. In patients who respond to medical therapy this
may be performed semi-electively during the same admission (and ideally
within 72 hours). Approximately 10% to 15% of patients fail to respond
(within 12 to 24 hours) or deteriorate after initial medical therapy and these
patients need urgent biliary decompression [98,119,120]. Delay in this
situation increases the chance of an adverse outcome [121].
Endoscopic biliary drainage
An ERCP with bile duct drainage or clearance is the treatment of choice
for decompressing the biliary system in acute cholangitis (Fig. 7). It has
a success rate of 90% to 98% and is superior to surgical or percutaneous
drainage in multiple studies [122–127]. Lai et al [124] randomized 83 patients
with acute cholangitis to undergo endoscopic or surgical decompression and
found that mortality (10% versus 32%) was signiﬁcantly lower in the
endoscopic arm [124]. Other studies have conﬁrmed this [123,126,128].
Fig. 7. Bile duct stones. Patient with acute cholangitis and a cholangiogram that demonstrates
multiple common bile duct stones, and a basket that has been inserted for endoscopic stone
removal (solid arrow).
1158
I.F. Yusoﬀ et al / Gastroenterol Clin N Am 32 (2003) 1145–1168
ERCP has also been shown to have lower morbidity rates, shorter length of
hospitalization, and a higher deﬁnitive success rate than percutaneous
drainage [125,127].
Endoscopic options are biliary drainage with a plastic stent or nasobiliary
catheter or endoscopic sphincterotomy (ES) and bile duct clearance. In the
critically ill or in patients with a coagulopathy, there are concerns that ES
may increase the risk of complications and procedure time [98]. Although
this has never been shown to be the case in clinical trials the concern is
legitimate, especially because biliary drainage without sphincterotomy is
safe and eﬀective in such patients [121,125,127]. In the only randomized trial
directly to compare use of nasobiliary catheter with biliary stent for acute
cholangitis, Lee et al [129] found both to be equally eﬀective but the stent
was associated with less postprocedural discomfort and avoided the
potential inadvertent removal [129]. In patients who are not critically ill,
ES and bile duct clearance should be attempted, and this is the deﬁnitive
procedure in patients who have had a cholecystectomy. Complications of
ERCP and ES include pancreatitis, bleeding, stone impaction, and
perforation and occur in 5% to 10%, with bleeding being a particular
problem in those with cholangitis [130]. Antibiotics should be continued
after successful bile duct clearance because patients remain at risk of
developing cholecystitis and empyema [131]. Total duration of antibiotic
therapy depends on response and the authors’ practice is to continue
therapy for 7 days. A Dutch study suggests, however, that in patients with
an uncomplicated course, and good response to biliary drainage, 3 days of
antibiotic therapy may be suﬃcient [132].
Percutaneous transhepatic biliary drainage
Percutaneous transhepatic biliary drainage can be performed successfully
in up to 90% of patients with biliary tract obstruction [133]. It has higher
rates of morbidity (30% to 80%) and mortality (5% to 15%) than
endoscopic drainage [1,125,133,134]. Nonetheless, percutaneous transhepatic biliary drainage may be preferred over ERCP in speciﬁc situations,
such as hepatolithiasis; intrasegmental cholangitis [135]; when the papilla is
inaccessible endoscopically (eg, after Roux-en-Y formation); or when ERCP
has failed. As with ERCP, caution must be taken to correct coagulopathies
preprocedurally.
Surgical biliary drainage
Open surgery has been used to treat cholangitis for almost 100 years. It
is associated with mortality rates of up to 40%, however, and is rarely used
as the ﬁrst-line method of biliary drainage [103,119,136]. When it is
performed, emergency surgery may be limited to choledochotomy, decompression, and T-tube insertion [98,103,119]. A proportion of patients
I.F. Yusoﬀ et al / Gastroenterol Clin N Am 32 (2003) 1145–1168
1159
treated endoscopically or percutaneously requires deﬁnitive surgical
intervention, and the mortality is low in patients who are able to undergo
this electively [1]. A clinical algorithm for the management of cholangitis is
presented in Fig. 8.
Management of the gallbladder after bile duct clearance
Whether subsequent cholecystectomy is indicated for patients with
cholelithiasis who have had an episode of cholangitis successfully treated
with ES and bile duct clearance is a matter of debate. The rationale for
proceeding to cholecystectomy is to prevent further biliary complications.
Management strategies need to be individualized and guided by risk factors
for surgery and further biliary complication. In retrospective and nonrandomized prospective studies, the risk of patients with common bile duct
stones developing subsequent biliary complications during follow-up has
ranged from 4% to 12% [137–141]. Four randomized controlled trials have
been reported that speciﬁcally address this issue [142–145]. Boerma et al
[142] studied 120 patients aged 18 to 80 years with proved symptomatic
common bile duct and concomitant gallbladder stones who underwent ES
and bile duct clearance. Patients were randomized to LC within 6 weeks of
endoscopic stone clearance or to a ‘‘wait and see’’ approach. During a mean
follow-up period of 30 months, 47% of patients in the wait and see group
had recurrent biliary symptoms compared with 2% in the LC group.
Furthermore, 37% of the wait and see group needed cholecystectomy.
Targarona et al [143] randomized 98 elderly and other high-risk patients
with symptoms likely caused by bile duct stones either to ES alone or open
surgery and found that after a mean follow-up of 17 months, biliary
symptoms recurred in 20% of the ES group and 6% of the surgery group.
Hammarstrom et al [144] randomized 83 patients with bile duct stones to ES
and stone removal or open surgery (cholecystectomy and bile duct
exploration) and found that after more than 5 years, 20% of the ES group
underwent cholecystectomy because of recurrent biliary symptoms, whereas
2% of patients in the surgery group had recurrent symptoms from bile duct
stones. During the follow-up period, nonbiliary mortality was signiﬁcantly
more common in the ES group. Panis et al [145] randomized 206 patients
with common bile duct stones to endoscopic therapy alone or surgery and
found early surgery was required in 19% in the endoscopic group, whereas
only 2% of the surgical group needed reoperation. Taken together these
studies strongly support the recommendation that patients with cholangitis
should undergo elective LC after bile duct clearance if they are ﬁt for
surgery (unless an open approach is known to be required). This may not
apply to Asian patients where bile duct stones may originate from
intrahepatic stones and hence cholecystectomy may not prevent further
biliary complications. Two nonrandomized prospective studies from Hong
Kong have not shown a beneﬁt of cholecystectomy over ES alone in
1160
I.F. Yusoﬀ et al / Gastroenterol Clin N Am 32 (2003) 1145–1168
Fig. 8. Clinical algorithm for the management of ascending cholangitis. *In selected clinical
scenarios PTBD may be preferred to ERCP (see text). ERCP, endoscopic retrograde
cholangiopancreatography; ES, endoscopic sphincterotomy; ESWL, extracorporeal shock
wave lithotripsy; LC, laparoscopic cholecystectomy; PTBD, percutaneous transhepatic biliary
drainage.
I.F. Yusoﬀ et al / Gastroenterol Clin N Am 32 (2003) 1145–1168
1161
preventing recurrent cholangitis or biliary complications in patients with
bile duct stones [139,146]. In contrast a retrospective study from Hong Kong
suggested that patients with bile duct stones treated with ES alone had an
increased risk of recurrent biliary symptoms when compared with those who
also underwent LC and the results of further prospective trials are awaited
[147]. Similarly, a recent randomized trial from Hong Kong showed that,
in patients with cholangitis and gallbladder stones but in the absence of
common bile duct stones, ES resulted in decreased durations of cholangitis
and hospital stay, but no reduced incidence of recurrent acute cholangitis
[148].
Summary
Cholelithiasis is a prevalent condition in Western populations. Most
cases are asymptomatic but complications can occur. Acute cholangitis,
cholecystitis, and gallstone pancreatitis are the most common biliary tract
emergencies and are usually caused by biliary calculi. Whenever possible,
acute cholecystitis should be treated with early LC. AAC is an uncommon
condition usually aﬀecting patients with signiﬁcant comorbidities. Treatment is usually with percutaneous cholecystostomy, which often is also the
only required therapy. Endoscopic drainage is the preferred form of biliary
decompression in acute cholangitis and these patients should subsequently
undergo elective LC unless unﬁt for surgery. Eﬀective and optimal management of biliary tract emergencies relies on close cooperation between
gastroenterologist, surgeon, and radiologist.
Acknowledgement
The authors thank Dr. Caroline Reinhold and Dr. Ida Khalili for the
MRI images.
References
[1] Kadakia SC. Biliary tract emergencies: acute cholecystitis, acute cholangitis, and acute
pancreatitis. Med Clin North Am 1993;77:1015–36.
[2] Lillemoe KD. Surgical treatment of biliary tract infections. Am Surg 2000;66:138–44.
[3] Indar A, Beckingham I. Acute cholecystitis. BMJ 2002;325:639–43.
[4] Shapiro MJ, Luchtefeld WB, Kurzweil S, Kaminski DL, Durham RM, Mazuski JE.
Acute acalculous cholecystitis in the critically ill. Am Surg 1994;60:335–9.
[5] Gallstones and laparoscopic cholecystectomy. NIH Consensus Statement 1992;10:1–28.
[6] Horton J, Bilhartz L. Gallstone disease and its complications. In: Feldman M, Friedman
L, Sleisenger M, editors. Sleisenger and Fordtran’s gastrointestinal and liver disease:
pathophysiology, diagnosis, management. Philadelphia: WB Saunders; 2002. p. 1065–90.
[7] Bates T, Harrison M, Lowe D, Lawson C, Padley N. Longitudinal study of gall stone
prevalence at necropsy. Gut 1992;33:103–7.
[8] Ingelﬁnger F. Digestive disease as a national problem, V. Gastroenterology 1968;55:102–4.
1162
I.F. Yusoﬀ et al / Gastroenterol Clin N Am 32 (2003) 1145–1168
[9] Friedman GD. Natural history of asymptomatic and symptomatic gallstones. Am J Surg
1993;165:399–404.
[10] Attili A, De Santis A, Capri R. The natural history of gallstones: the GREPCO
experience. Hepatology 1995;21:656–9.
[11] Thistle J, Cleary P, Lachin J, Tyor M, Hersh T. The natural history of cholelithiasis: the
National Cooperative Gallstone Study. Ann Intern Med 1984;101:171–5.
[12] Gracie W, Ransohoﬀ D. The natural history of silent gallstones: the innocent gallstone is
not a myth. N Engl J Med 1982;307:798–800.
[13] McSherry C, Ferstenberg H, Calhoun W, Lahman E, Virshup M. The natural history of
diagnosed gallstone disease in symptomatic and asymptomatic patients. Ann Surg
1985;202:59–63.
[14] Schwesinger WH, Diehl AK. Changing indications for laparoscopic cholecystectomy:
stones without symptoms and symptoms without stones. Surg Clin North Am 1996;
76:493–504.
[15] Myers SI, Bartula L. Human cholecystitis is associated with increased gallbladder
prostaglandin I2 and prostaglandin E2 synthesis. Hepatology 1992;16:1176–9.
[16] Goldman G, Kahn PJ, Alon R, Wiznitzer T. Biliary colic treatment and acute cholecystitis
prevention by prostaglandin inhibitor. Dig Dis Sci 1989;34:809–11.
[17] Claesson BE, Holmlund DE, Matzsch TW. Microﬂora of the gallbladder related to
duration of acute cholecystitis. Surg Gynecol Obstet 1986;162:531–5.
[18] Claesson BE. Microﬂora of the biliary tree and liver: clinical correlates. Dig Dis
1986;4:93–118.
[19] Kuo CH, Changchien CS, Chen JJ, Tai DI, Chiou SS, Lee CM. Septic acute cholecystitis.
Scand J Gastroenterol 1995;30:272–5.
[20] Kalloo AN, Kantsevoy SV. Gallstones and biliary disease. Prim Care 2001;28:591–606.
[21] Raine PA, Gunn AA. Acute cholecystitis. Br J Surg 1975;62:697–700.
[22] Singer AJ, McCracken G, Henry MC, Thode HC Jr, Cabahug CJ. Correlation among
clinical, laboratory, and hepatobiliary scanning ﬁndings in patients with suspected acute
cholecystitis. Ann Emerg Med 1996;28:267–72.
[23] 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.
[24] Hammarstrom L, Ranstam J. Factors predictive of bile duct stones in patients with acute
calculous cholecystitis. Dig Surg 1998;15:323–7.
[25] Carroll BA. Preferred imaging techniques for the diagnosis of cholecystitis and
cholelithiasis. Ann Surg 1989;210:1–12.
[26] Soiva M, Haveri M, Taavitsainen M, Suramo I. The value of routine sonography in
clinically suspected acute cholecystitis. Scand J Gastroenterol 1986;21:70–4.
[27] Ralls PW, Colletti PM, Lapin SA, et al. Real-time sonography in suspected acute
cholecystitis: prospective evaluation of primary and secondary signs. Radiology
1985;155:767–71.
[28] Schoﬁeld PF, Hulton NR, Baildam AD. Is it acute cholecystitis? Ann R Coll Surg Engl
1986;68:14–6.
[29] Martinez A, Bona X, Velasco M, Martin J. Diagnostic accuracy of ultrasound in acute
cholecystitis. Gastrointest Radiol 1986;11:334–8.
[30] Herlin P, Alinder G, Karp W, Holmin T. Contrast tomography of the gallbladder
wall and ultrasonography in the diagnosis of acute cholecystitis. Br J Surg 1984;71:
850–3.
[31] Samuels BI, Freitas JE, Bree RL, Schwab RE, Heller ST. A comparison of radionuclide
hepatobiliary imaging and real-time ultrasound for the detection of acute cholecystitis.
Radiology 1983;147:207–10.
[32] Kalimi R, Gecelter GR, Caplin D, et al. Diagnosis of acute cholecystitis: sensitivity of
sonography, cholescintigraphy, and combined sonography-cholescintigraphy. J Am Coll
Surg 2001;193:609–13.
I.F. Yusoﬀ et al / Gastroenterol Clin N Am 32 (2003) 1145–1168
1163
[33] Mauro MA, McCartney WH, Melmed JR. Hepatobiliary scanning with 99mTc-PIPIDA
in acute cholecystitis. Radiology 1982;142:193–7.
[34] Szlabick RE, Catto JA, Fink-Bennett D, Ventura V. Hepatobiliary scanning in the
diagnosis of acute cholecystitis. Arch Surg 1980;115:540–4.
[35] Carr TG, Kazarian KK, Smego DR, Barone JE. Radionuclide cholescintigraphy in
patients with suspected biliary tract obstruction. Am Surg 1991;57:673–5.
[36] Cabellon S Jr, Brown JM, Cavanaugh DG. Accuracy of the hepatobiliary scan in acute
cholecystitis. Am J Surg 1984;148:607–8.
[37] Shea JA, Berlin JA, Escarce JJ, et al. Revised estimates of diagnostic test sensitivity and
speciﬁcity in suspected biliary tract disease. Arch Intern Med 1994;154:2573–81.
[38] Park MS, Yu JS, Kim YH, et al. Acute cholecystitis: comparison of MR cholangiography
and US. Radiology 1998;209:781–5.
[39] Akriviadis EA, Hatzigavriel M, Kapnias D, Kirimlidis J, Markantas A, Garyfallos A.
Treatment of biliary colic with diclofenac: a randomized, double-blind, placebocontrolled study. Gastroenterology 1997;113:225–31.
[40] Jarvinen H, Renkonen OV, Palmu A. Antibiotics in acute cholecystitis. Ann Clin Res
1978;10:247–51.
[41] Bjorvatn B. Cholecystitis–etiology and treatment–microbiological aspects. Scand J
Gastroenterol Suppl 1984;90:65–70.
[42] Yellin AE, Berne TV, Appleman MD, et al. A randomized study of cefepime versus the
combination of gentamicin and mezlocillin as an adjunct to surgical treatment in patients
with acute cholecystitis. Surg Gynecol Obstet 1993;177:23–9; discussion 35–40.
[43] Lau WY, Yuen WK, Chu KW, Chong KK, Li AK. Systemic antibiotic regimens for acute
cholecystitis treated by early cholecystectomy. Aust N Z J Surg 1990;60:539–43.
[44] Linden W, Sunzel H. Early versus delayed operation for acute cholecystitis: a controlled
trial. Am J Surg 1970;120:7–13.
[45] McArthur P, Cuschieri A, Sells R, Shields R. Controlled clinical trial comparing early
with interval cholecystectomy for acute cholecystitis. Br J Surg 1975;68:850–2.
[46] Lahtinen J, Alhava EM, Aukee S. Acute cholecystitis treated by early and delayed
surgery: a controlled clinical trial. Scand J Gastroenterol 1978;13:673–8.
[47] Jarvinen H, Hastbacka J. Early cholecystectomy for acute cholecystitis: a prospective
randomized trial. Ann Surg 1980;191:501–5.
[48] Lai PB, Kwong KH, Leung KL, et al. Randomized trial of early versus delayed
laparoscopic cholecystectomy for acute cholecystitis. Br J Surg 1998;85:764–7.
[49] Lo CM, Liu CL, Fan ST, Lai EC, Wong J. Prospective randomized study of early versus
delayed laparoscopic cholecystectomy for acute cholecystitis. Ann Surg 1998;227:461–7.
[50] Chandler CF, Lane JS, Ferguson P, Thompson JE, Ashley SW. Prospective evaluation of
early versus delayed laparoscopic cholecystectomy for treatment of acute cholecystitis.
Am Surg 2000;66:896–900.
[51] Brodsky A, Matter I, Sabo E, Cohen A, Abrahamson J, Eldar S. Laparoscopic
cholecystectomy for acute cholecystitis: can the need for conversion and the probability of
complications be predicted? A prospective study. Surg Endosc 2000;14:755–60.
[52] Willsher PC, Sanabria JR, Gallinger S, Rossi L, Strasberg S, Litwin DE. Early
laparoscopic cholecystectomy for acute cholecystitis: a safe procedure. J Gastrointest Surg
1999;3:50–3.
[53] Koo KP, Thirlby RC. Laparoscopic cholecystectomy in acute cholecystitis. What is the
optimal timing for operation? Arch Surg 1996;131:540–4; discussion 544–5.
[54] Pessaux P, Tuech JJ, Rouge C, Duplessis R, Cervi C, Arnaud JP. Laparoscopic
cholecystectomy in acute cholecystitis: a prospective comparative study in patients with
acute vs. chronic cholecystitis. Surg Endosc 2000;14:358–61.
[55] Pessaux P, Regenet N, Tuech JJ, Rouge C, Bergamaschi R, Arnaud JP. Laparoscopic
versus open cholecystectomy: a prospective comparative study in the elderly with acute
cholecystitis. Surg Laparosc Endosc Percutan Tech 2001;11:252–5.
1164
I.F. Yusoﬀ et al / Gastroenterol Clin N Am 32 (2003) 1145–1168
[56] Rattner D, Ferguson C, Warshaw A. Factors associated with successful laparoscopic
cholecystectomy for acute cholecystitis. Ann Surg 1993;217:233–6.
[57] Strasberg SM. Laparoscopic biliary surgery. Gastroenterol Clin North Am 1999;28:117–32.
[58] Boland G, Lee M, Leung J, Mueller P. Percutaneous cholecystostomy in critically ill
patients: early response and ﬁnal outcomes in 82 patients. AJR Am J Roentgenol
1994;163:339–42.
[59] Borzellino G, de Manzoni G, Ricci F, Castaldini G, Guglielmi A, Cordiano C. Emergency
cholecystostomy and subsequent cholecystectomy for acute gallstone cholecystitis in the
elderly. Br J Surg 1999;86:1521–5.
[60] Hamy A, Visset J, Likholatnikov D, et al. Percutaneous cholecystostomy for acute
cholecystitis in critically ill patients. Surgery 1997;121:398–401.
[61] Hultman CS, Herbst CA, McCall JM, Mauro MA. The eﬃcacy of percutaneous
cholecystostomy in critically ill patients. Am Surg 1996;62:263–9.
[62] Lee KT, Wong SR, Cheng JS, Ker CG, Sheen PC, Liu YE. Ultrasound-guided
percutaneous cholecystostomy as an initial treatment for acute cholecystitis in elderly
patients. Dig Surg 1998;15:328–32.
[63] Patel M, Miedema BW, James MA, Marshall JB. Percutaneous cholecystostomy is an
eﬀective treatment for high-risk patients with acute cholecystitis. Am Surg 2000;66:33–7.
[64] Berber E, Engle KL, String A, et al. Selective use of tube cholecystostomy with interval
laparoscopic cholecystectomy in acute cholecystitis. Arch Surg 2000;135:341–6.
[65] Schwesinger WH, Sirinek KR, Strodel WE III. Laparoscopic cholecystectomy for biliary
tract emergencies: state of the art. World J Surg 1999;23:334–42.
[66] Patterson EJ, McLoughlin RF, Mathieson JR, Cooperberg PL, MacFarlane JK. An
alternative approach to acute cholecystitis: percutaneous cholecystostomy and interval
laparoscopic cholecystectomy. Surg Endosc 1996;10:1185–8.
[67] Spira RM, Nissan A, Zamir O, Cohen T, Fields SI, Freund HR. Percutaneous
transhepatic cholecystostomy and delayed laparoscopic cholecystectomy in critically ill
patients with acute calculus cholecystitis. Am J Surg 2002;183:62–6.
[68] Kim HJ, Lee SK, Kim MH, et al. Safety and usefulness of percutaneous transhepatic
cholecystoscopy examination in high-risk surgical patients with acute cholecystitis.
Gastrointest Endosc 2000;52:645–9.
[69] Hatzidakis AA, Prassopoulos P, Petinarakis I, et al. Acute cholecystitis in high-risk
patients: percutaneous cholecystostomy vs conservative treatment. Eur Radiol 2002;
12:1778–84.
[70] 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.
[71] Howard DE, Fromm H. Nonsurgical management of gallstone disease. Gastroenterol
Clin North Am 1999;28:133–44.
[72] Cox MR, Wilson TG, Luck AJ, Jeans PL, Padbury RT, Toouli J. Laparoscopic
cholecystectomy for acute inﬂammation of the gallbladder. Ann Surg 1993;218:630–4.
[73] Unger SW, Rosenbaum G, Unger HM, Edelman DS. A comparison of laparoscopic and
open treatment of acute cholecystitis. Surg Endosc 1993;7:408–11.
[74] Estes NC, McElhinney C, Estes MA, Opie H, Johnson M. Acute cholecystitis treated
urgently by nonselective laparoscopic cholecystectomy. Am Surg 1996;62:598–601;
discussion 601–2.
[75] Steiner CA, Bass EB, Talamini MA, Pitt HA, Steinberg EP. Surgical rates and operative
mortality for open and laparoscopic cholecystectomy in Maryland. N Engl J Med
1994;330:403–8.
[76] Bedirli A, Sakrak O, Sozuer EM, Kerek M, Guler I. Factors eﬀecting the complications in
the natural history of acute cholecystitis. Hepatogastroenterology 2001;48:1275–8.
[77] Tsai CJ, Wu CS. Risk factors for perforation of gallbladder: a combined hospital study in
a Chinese population. Scand J Gastroenterol 1991;26:1027–34.
I.F. Yusoﬀ et al / Gastroenterol Clin N Am 32 (2003) 1145–1168
1165
[78] Bilhartz L. Acalculous cholecystitis, cholesterolosis, adenomyomatosis and polyps of the
gallbladder. In: Feldman M, Friedman L, Sleisenger M, editors. Sleisenger and Fordtran’s
gastrointestinal and liver diseases: pathophysiology, diagnosis, management. Philadelphia: WB Saunders; 2002. p. 1106–30.
[79] Barrett D, Chadwick S, Fleming J. Acalculous cholelithiasis: a misnomer. J R Soc Med
1988;81:664.
[80] Kalliafas S, Ziegler DW, Flancbaum L, Choban PS. Acute acalculous cholecystitis:
incidence, risk factors, diagnosis, and outcome. Am Surg 1998;64:471–5.
[81] Fisher RL. Hepatobiliary abnormalities associated with total parenteral nutrition.
Gastroenterol Clin North Am 1989;18:645–66.
[82] Savoca PE, Longo WE, Pasternak B, Gusberg RJ. Does visceral ischemia play a role in
the pathogenesis of acute acalculous cholecystitis? J Clin Gastroenterol 1990;12:33–6.
[83] Parithivel VS, Gerst PH, Banerjee S, Parikh V, Albu E. Acute acalculous cholecystitis in
young patients without predisposing factors. Am Surg 1999;65:366–8.
[84] Savoca PE, Longo WE, Zucker KA, McMillen MM, Modlin IM. The increasing
prevalence of acalculous cholecystitis in outpatients: results of a 7-year study. Ann Surg
1990;211:433–7.
[85] Warren BL. Small vessel occlusion in acute acalculous cholecystitis. Surgery
1992;111:163–8.
[86] Hakala T, Nuutinen P, Ruokonen E, Alhava E. Microangiopathy in acute acalculous
cholecystitis. Br J Surg 1997;84:1249–52.
[87] Cornwell E, Rodriguez A, Mirvis S, Shorr R. Acute acalculous cholecystitis in critically
injured patients: preoperative diagnostic imaging. Ann Surg 1989;210:52–5.
[88] Molenat F, Boussuges A, Valantin V, Sainty JM. Gallbladder abnormalities in medical
ICU patients: an ultrasonographic study. Intensive Care Med 1996;22:356–8.
[89] Mariat G, Mahul P, Prev TN, et al. Contribution of ultrasonography and cholescintigraphy to the diagnosis of acute acalculous cholecystitis in intensive care unit patients.
Intensive Care Med 2000;26:1658–63.
[90] Blankenberg F, Wirth R, Jeﬀrey RB Jr, Mindelzun R, Francis I. Computed tomography
as an adjunct to ultrasound in the diagnosis of acute acalculous cholecystitis. Gastrointest
Radiol 1991;16:149–53.
[91] Fink-Bennet D, Balan H, Robbins T, Tsai D. Morphine-augmented cholescintigraphy: its
eﬃcacy in detecting acute cholecystitis. J Nucl Med 1991;32:1231–5.
[92] Arnot RS. Laparoscopy and acalculous cholecystitis. Aust N Z J Surg 1994;64:405–6.
[93] Shirai Y, Tsukada K, Kawaguchi H, Ohtani T, Muto T, Hatakeyama K. Percutaneous
transhepatic cholecystostomy for acute acalculous cholecystitis. Br J Surg 1993;80:1440–2.
[94] Kim KH, Sung CK, Park BK, Kim WK, Oh CW, Kim KS. Percutaneous gallbladder
drainage for delayed laparoscopic cholecystectomy in patients with acute cholecystitis.
Am J Surg 2000;179:111–3.
[95] Johlin FC Jr, Neil GA. Drainage of the gallbladder in patients with acute acalculous
cholecystitis by transpapillary endoscopic cholecystotomy. Gastrointest Endosc 1993;39:
645–51.
[96] Andrew DJ, Johnson SE. Acute suppurative cholangitis, a medical and surgical
emergency: a review of ten years experience emphasizing early recognition. Am J
Gastroenterol 1970;54:141–54.
[97] Dow RW, Lindenauer SM. Acute obstructive suppurative cholangitis. Ann Surg
1969;169:272–6.
[98] Hanau LH, Steigbigel NH. Acute (ascending) cholangitis. Infect Dis Clin North Am
2000;14:521–46.
[99] Csendes A, Fernandez M, Uribe P. Bacteriology of the gallbladder bile in normal subjects.
Am J Surg 1975;129:629–31.
[100] Carpenter HA. Bacterial and parasitic cholangitis. Mayo Clin Proc 1998;73:473–8.
[101] Cetta F. The route of infection in patients with bactibilia. World J Surg 1983;7:562.
1166
I.F. Yusoﬀ et al / Gastroenterol Clin N Am 32 (2003) 1145–1168
[102] Shimada K, Noro T, Inamatsu T, Urayama K, Adachi K. Bacteriology of acute
obstructive suppurative cholangitis of the aged. J Clin Microbiol 1981;14:522–6.
[103] Boey JH, Way LW. Acute cholangitis. Ann Surg 1980;191:264–70.
[104] O’Connor MJ, Schwartz ML, McQuarrie DG, Sumer HW. Acute bacterial cholangitis:
an analysis of clinical manifestation. Arch Surg 1982;117:437–41.
[105] Einstein DM, Lapin SA, Ralls PW, Halls JM. The insensitivity of sonography in the
detection of choledocholithiasis. AJR Am J Roentgenol 1984;142:725–8.
[106] Baron RL, Stanley RJ, Lee JK, et al. A prospective comparison of the evaluation of
biliary obstruction using computed tomography and ultrasonography. Radiology 1982;
145:91–8.
[107] Gibson RN, Yeung E, Thompson JN, et al. Bile duct obstruction: radiologic evaluation
of level, cause, and tumor resectability. Radiology 1986;160:43–7.
[108] Pasanen PA, Partanen K, Pikkarainen P, Alhava E, Pirinen A, Janatuinen E. Diagnostic
accuracy of ultrasound, computed tomography, and endoscopic retrograde cholangiopancreatography in the detection of obstructive jaundice. Scand J Gastroenterol
1991;26:1157–64.
[109] Bader TR, Braga L, Beavers KL, Semelka RC. MR imaging ﬁndings of infectious
cholangitis. Magn Reson Imaging 2001;19:781–8.
[110] Menezes N, Marson LP, debeaux AC, Muir IM, Auld CD. Prospective analysis of
a scoring system to predict choledocholithiasis. Br J Surg 2000;87:1176–81.
[111] Barkun AN, Barkun JS, Fried GM, et al. Useful predictors of bile duct stones in patients
undergoing laparoscopic cholecystectomy. McGill Gallstone Treatment Group. Ann Surg
1994;220:32–9.
[112] Desai T, Tsang T. Aminoglycoside nephrotoxicity in obstructive jaundice. Am J Surg
1988;85:47–50.
[113] Leung JW, Ling TK, Chan RC, et al. Antibiotics, biliary sepsis, and bile duct stones.
Gastrointest Endosc 1994;40:716–21.
[114] Thompson JE Jr, Pitt HA, Doty JE, Coleman J, Irving C. Broad spectrum
penicillin as an adequate therapy for acute cholangitis. Surg Gynecol Obstet 1990;171:
275–82.
[115] Chacon JP, Criscuolo PD, Kobata CM, Ferraro JR, Saad SS, Reis C. Prospective
randomized comparison of peﬂoxacin and ampicillin plus gentamicin in the treatment
of bacteriologically proven biliary tract infections. J Antimicrob Chemother 1990;26
(suppl B):167–72.
[116] Karachalios GN, Nasiopoulou DD, Bourlinou PK, Reppa A. Treatment of acute biliary
tract infections with oﬂoxacin: a randomized, controlled clinical trial. Int J Clin
Pharmacol Ther 1996;34:555–7.
[117] Karachalios GN, Zografos G, Patrikakos V, Nassopoulou D, Kehagioglou K. Biliary
tract infections treated with ciproﬂoxacin. Infection 1993;21:262–4.
[118] Sung JJ, Lyon DJ, Suen R, et al. Intravenous ciproﬂoxacin as treatment for patients with
acute suppurative cholangitis: a randomized, controlled clinical trial. J Antimicrob
Chemother 1995;35:855–64.
[119] Lai EC, Tam PC, Paterson IA, et al. Emergency surgery for severe acute cholangitis: the
high-risk patients. Ann Surg 1990;211:55–9.
[120] Thompson JE Jr, Tompkins RK, Longmire WP Jr. Factors in management of acute
cholangitis. Ann Surg 1982;195:137–45.
[121] Boender J, Nix GA, de Ridder MA, et al. Endoscopic sphincterotomy and biliary
drainage in patients with cholangitis due to common bile duct stones. Am J Gastroenterol
1995;90:233–8.
[122] Leung JW, Chung SC, Sung JJ, Banez VP, Li AK. Urgent endoscopic drainage for acute
suppurative cholangitis. Lancet 1989;1:1307–9.
[123] Leese T, Neoptolemos JP, Baker AR, Carr-Locke DL. Management of acute cholangitis
and the impact of endoscopic sphincterotomy. Br J Surg 1986;73:988–92.
I.F. Yusoﬀ et al / Gastroenterol Clin N Am 32 (2003) 1145–1168
1167
[124] Lai EC, Mok FP, Tan ES, et al. Endoscopic biliary drainage for severe acute cholangitis.
N Engl J Med 1992;326:1582–6.
[125] Sugiyama M, Atomi Y. Treatment of acute cholangitis due to choledocholithiasis in
elderly and younger patients. Arch Surg 1997;132:1129–33.
[126] Chijiiwa K, Kozaki N, Naito T, Kameoka N, Tanaka M. Treatment of choice for
choledocholithiasis in patients with acute obstructive suppurative cholangitis and liver
cirrhosis. Am J Surg 1995;170:356–60.
[127] Sugiyama M, Atomi Y. The beneﬁts of endoscopic nasobiliary drainage without
sphincterotomy for acute cholangitis. Am J Gastroenterol 1998;93:2065–8.
[128] Ditzel H, Schaﬀalitzky de Muckadell OB. Endoscopic sphincterotomy in acute cholangitis
due to choledocholithiasis. Hepatogastroenterology 1990;37:204–7.
[129] Lee DW, Chan AC, Lam YH, et al. Biliary decompression by nasobiliary catheter or
biliary stent in acute suppurative cholangitis: a prospective randomized trial. Gastrointest
Endosc 2002;56:361–5.
[130] Freeman ML, Nelson DB, Sherman S, et al. Complications of endoscopic biliary
sphincterotomy. N Engl J Med 1996;335:909–18.
[131] Davidson BR, Neoptolemos JP, Carr-Locke DL. Endoscopic sphincterotomy for
common bile duct calculi in patients with gall bladder in situ considered unﬁt for
surgery. Gut 1988;29:114–20.
[132] van Lent AU, Bartelsman JF, Tytgat GN, Speelman P, Prins JM. Duration of antibiotic
therapy for cholangitis after successful endoscopic drainage of the biliary tract.
Gastrointest Endosc 2002;55:518–22.
[133] Joseph PK, Bizer LS, Sprayregen SS, Gliedman ML. Percutaneous transhepatic biliary
drainage: results and complications in 81 patients. JAMA 1986;255:2763–7.
[134] Pessa ME, Hawkins IF, Vogel SB. The treatment of acute cholangitis: percutaneous
transhepatic biliary drainage before deﬁnitive therapy. Ann Surg 1987;205:389–92.
[135] Yeh YH, Huang MH, Yang JC, Mo LR, Lin J, Yueh SK. Percutaneous trans-hepatic
cholangioscopy and lithotripsy in the treatment of intrahepatic stones: a study with 5 year
follow-up. Gastrointest Endosc 1995;42:13–8.
[136] Raraty MG, Finch M, Neoptolemos JP. Acute cholangitis and pancreatitis secondary to
common duct stones: management update. World J Surg 1998;22:1155–61.
[137] 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.
[138] Escourrou J, Cordova JA, Lazorthes F, Frexinos J, Ribet A. Early and late complications
after endoscopic sphincterotomy for biliary lithiasis with and without the gall bladder in
situ. Gut 1984;25:598–602.
[139] Lai KH, Lin LF, Lo GH, et al. Does cholecystectomy after endoscopic sphincterotomy prevent the recurrence of biliary complications? Gastrointest Endosc 1999;49:
483–7.
[140] Welbourn CR, Beckly DE, Eyre-Brook IA. Endoscopic sphincterotomy without
cholecystectomy for gall stone pancreatitis. Gut 1995;37:119–20.
[141] 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.
[142] Boerma D, Rauws EA, Keulemans YC, et al. Wait-and-see policy or laparoscopic
cholecystectomy after endoscopic sphincterotomy for bile-duct stones: a randomised trial.
Lancet 2002;360:761–5.
[143] Targarona EM, Ayuso RM, Bordas JM, et al. Randomised trial of endoscopic
sphincterotomy with gallbladder left in situ versus open surgery for common bile duct
calculi in high-risk patients. Lancet 1996;347:926–9.
[144] Hammarstrom LE, 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.
1168
I.F. Yusoﬀ et al / Gastroenterol Clin N Am 32 (2003) 1145–1168
[145] Panis Y, Suc B, Escat J. Surgery versus endoscopic sphincterotomy for choledocholithiasis: results of a prospective randomized study. Gastroenterology 1995;108:A431.
[146] Hui CK, Lai KC, Yuen MF, Ng MM, Lam SK, Lai CL. Role of cholecystectomy in
preventing recurrent cholangitis. Gastrointest Endosc 2002;56:55–60.
[147] Poon RT, Liu CL, Lo CM, et al. Management of gallstone cholangitis in the era of
laparoscopic cholecystectomy. Arch Surg 2001;136:11–6.
[148] Hui CK, Lai KC, Wong WM, Yuen MF, Lam SK, Lai CL. A randomized controlled trial
of endoscopic sphincterotomy in acute cholangitis without common bile duct stones. Gut
2002;51:245–7.