1. health and fitness
2. disease

9
Hilar Cholangiocarcinoma
PIERRE F. SALDINGER, MD
WILLIAM R. JARNAGIN, MD
LESLIE H. BLUMGART, MD, FACS, FRCS (ENG, EDIN, GLAS)
Malignant tumors of the bile ducts remain a major
management challenge. They occur most commonly
in the proximal bile duct, at the hepatic duct confluence (hilar cholangiocarcinoma), or in the distal common bile duct near the papilla (distal cholangiocarcinoma) (Fig. 9–1). Resection offers the best chance of
long-term survival, but many patients present with
advanced disease that is not amenable to extirpation.
The assessment and treatment of distal bile duct cancers is similar to that of cancers of the head of the
pancreas. This chapter focuses on management
issues specific to hilar cholangiocarcinoma.
there are several conditions that are associated with
an increased risk.
Primary Sclerosing Cholangitis
Perhaps the most common associated condition in
Western countries is primary sclerosing cholangitis
(PSC), an autoimmune disease characterized by
EPIDEMIOLOGY
Cholangiocarcinoma is an uncommon disease. The
annual incidence in the United States is 1 to 2 per
100,000, and it accounts for approximately 2 percent
of all cancers.1 Men and women are affected in
nearly equal proportions. Although occasionally
seen in young patients, cholangiocarcinoma is primarily a disease of the elderly. The majority of
patients are over 65 years of age, and the peak incidence occurs in the eighth decade of life.1 Untreated,
hilar cholangiocarcinoma generally results in death
within 12 months, from liver failure or from complications arising from biliary tract obstruction.
ETIOLOGY
Cholangiocarcinoma usually occurs sporadically,
and most patients have no obvious risk factors. While
the etiology of cholangiocarcinoma is unknown,
Figure 9–1. Diagram illustrating the anatomy of the extrahepatic
biliary tree. (CD = cystic duct; GB = gallbladder; LHD = left hepatic
duct; RHD = right hepatic duct.)
193
194
HEPATOBILIARY CANCER
inflammation of the periductal tissues, ultimately
resulting in multifocal strictures of the intrahepatic
and extrahepatic bile ducts.2,3 The natural history of
PSC is quite variable, and the true incidence of
cholangiocarcinoma is unknown. The reported incidence in PSC ranges from 8 to 40 percent.2,3 Unlike
most patients with sporadic cholangiocarcinoma of
the extrahepatic biliary tree, patients with PSC are at
risk for multifocal disease that is often not amenable
to resection.
Congenital Biliary Cystic Disease
The increased risk of cholangiocarcinoma in patients
with congenital biliary cystic disease (choledochal
cysts, Caroli’s disease) is well described.4 Malignant
degeneration is uncommon in choledochal cysts that
have been completely excised early. However, the
incidence of cancer increases substantially (approximately 15 to 20%) in patients who are not treated until
after the age of 20 years or in those previously treated
by cyst drainage.5,6 The reason for the high incidence
of cancer in patients with cystic diseases appears to be
related to an abnormal choledochopancreatic duct
junction that predisposes to reflux of pancreatic
secretions into the biliary tree, bacterial contamination, and chronic inflammation.5–7 An increased incidence of cholangiocarcinoma has also been reported
in patients subjected to transduodenal sphincteroplasty,8 and a similar mechanism may be responsible.
Hepatolithiasis and Biliary Parasites
Hepatolithiasis, also known as recurrent pyogenic
cholangiohepatitis or Oriental cholangiohepatitis, is
prevalent in Japan and parts of Southeast Asia.
Obstruction of intrahepatic ducts leads to chronic
recurrent episodes of cholangitis and stricture forma-
Institution
UCLA (1981)†
Mayo Clinic (1993)12
Johns Hopkins (1996)13
MSKCC (1998)14
tion.9–11 Approximately 10 percent of patients will
develop cholangiocarcinoma.10 Biliary parasites
(Clonorchis sinensis and Opisthorchis viverrini) are
also prevalent in parts of Asia and are similarly associated with an increased risk of cholangiocarcinoma.3
LOCATION
Although cholangiocarcinoma can arise anywhere
within the biliary tree, hilar cholangiocarcinoma or
tumors involving the biliary confluence are the most
common (see Fig. 9–1). In most large series, the proportion of patients with tumors involving the hilus
ranges from 40 to 60 percent (Table 9–1).12–14 Tumors
of the distal bile duct are somewhat less common,
accounting for 20 to 30 percent of all cholangiocarcinomas and 5 to 10 percent of all periampullary
tumors.13,15,16 Approximately 10 percent of cholangiocarcinomas arise within the intrahepatic biliary
tree.17–19 These tumors usually present as an intrahepatic mass, and although uncommon, jaundice may
result from intrabiliary tumor extension (Fig. 9–2).
HISTOPATHOLOGY
The overwhelming majority of cholangiocarcinomas
are adenocarcinomas, often well differentiated and
mucin producing.1,20
There are three well-described macroscopic subtypes of cholangiocarcinoma: sclerosing, nodular,
and papillary.20 Sclerosing tumors account for the
majority of cases. Sclerosing tumors are very firm
and cause an annular thickening of the bile duct,
often with diffuse infiltration and fibrosis of the
periductal tissues (Fig. 9–3). Nodular tumors are
characterized by a firm irregular nodule of tumor
that projects into the lumen of the duct. Features of
both types are often seen, hence the frequently used
Table 9–1. INCIDENCE OF HILAR CHOLANGIOCARCINOMA IN SELECTED SERIES
Years*
Patients with Cholangiocarcinoma
Patients with Hilar Cholangiocarcinoma
24
9
23
6
96
171
294
225
47
79
197
90
(49%)
(46%)
(67%)
(40%)
MSKCC = Memorial Sloan-Kettering Cancer Center; UCLA = University of California, Los Angeles.
*Time interval over which patients were accumulated.
†
Reported in Tompkins RK, Thomas D, Wile A, Longmire WP Jr. Prognostic factors in bile duct carcinoma: analysis of 96 cases. Ann Surg 1981;194:447–57.
Hilar Cholangiocarcinoma
descriptor “nodular-sclerosing.” The papillary variant accounts for approximately 10 percent of all
cholangiocarcinomas and is more common in the
distal bile duct.21 A polypoid mass that expands
rather than contracts the duct is a characteristic feature (Fig. 9–4). Although papillary tumors may grow
to significant size and appear surgically unapproachable (based on radiographic studies), they often arise
from a well-defined stalk and histologically may be
confined to the superficial layers of the duct wall
(Fig. 9–5). Recognition of papillary cholangiocarcinomas is important since they are more often
resectable and have a more favorable prognosis than
the other types.3
Longitudinal spread along the duct wall and
periductal tissues is an important pathologic feature
A
195
of cholangiocarcinomas.20 There may be substantial
extension of tumor beneath an intact epithelial lining—as much as 2 cm proximally and 1 cm distally.22 The full tumor extent may thus be underestimated by radiographic studies and may not be fully
appreciated by palpation at the time of resection.
This feature underscores the importance of checking
all resection margins with frozen-section histology
at operation.
STAGING
According to the American Joint Commission on
Cancer (AJCC), the staging of extrahepatic cholangiocarcinomas is based on the extent of the primary
tumor (T stage), the extent of regional lymph node
B
Figure 9–2. Images from a patient with an intrahepatic cholangiocarcinoma and jaundice. A, Cross-sectional computed tomography
image showing dilated left biliary tree (arrow) but no clearly defined
mass. B, Cross-sectional magnetic resonance cholangiopancreatography (MRCP) image showing a heterogeneous mass in segment IV
(arrow). Dilated bile ducts appear as white areas. C, Coronal MRCP
reconstruction showing the tumor growing down the left hepatic duct
and extending across the right hepatic duct and into the common
hepatic duct (arrow). The dilated bile ducts again appear as white
areas. (Reproduced with permission from Jarnagin WR, Saldinger PF,
Blumgart LH. Cancer of the bile ducts: the hepatic ducts and common
bile duct. In: Blumgart LH, Fong Y, editors. Surgery of the liver and biliary tract. 3rd ed. Edinburgh [UK]: Churchill Livingstone; 2000.)
C
196
HEPATOBILIARY CANCER
involvement (N stage), and the presence of distant
metastases (M stage) (Table 9–2). An alternative
staging system proposed by Bismuth and Corlette
classifies cholangiocarcinomas on the basis of their
location with respect to the hilus and on the extent of
ductal involvement.23 The AJCC staging is based
largely on pathologic criteria and has little clinical
applicability. The majority of patients in our practice
have T3 (stage 4A) tumors based on invasion into
the liver, but this alone says very little about their
resectability. Moreover, this finding does not correlate with survival, provided that complete resection
A
A
B
Figure 9–3. A, Endoscopic cholangiogram showing the typical irregular biliary stricture characteristic of sclerosing adenocarcinomas
(arrow). These tumors cause a circumferential thickening of the duct
wall and periductal fibrosis, which ultimately obliterates the lumen.
(Reproduced with permission from Jarnagin WR, Saldinger PF, Blumgart LH. Cancer of the bile ducts: the hepatic ducts and common bile
duct. In: Blumgart LH, Fong Y, editors. Surgery of the liver and biliary
tract. 3rd ed. Edinburgh [UK]: Churchill Livingstone; 2000.) B, Coronal
magnetic resonance cholangiopancreatography reconstruction showing an infiltrating tumor involving the hepatic duct confluence (arrow).
The right and left intrahepatic ducts, which appear white, are dilated.
B
Figure 9–4. A, Transhepatic cholangiogram showing a markedly
dilated bile duct from the confluence of the right and left hepatic
ducts to the ampulla of Vater. Filling defects are apparent throughout
the length of the duct (black arrows). A percutaneous biliary stent is
in place (white arrow). B, Cross-sectional computed tomography
image of the same patient. The stent (white arrowhead) is seen
within the duct, adjacent to a large tumor mass (white arrow). The
underlying portal vein (black arrow) is free, and there is no evidence
of lobar atrophy.
Hilar Cholangiocarcinoma
197
A
B
C
Figure 9–5. A, Excised bile duct from the
patient discussed in Fig. 9–4. The duct has been
opened longitudinally to reveal two separate polypoid masses (arrows). B, View looking down the
incised bile duct, with one of the tumors seen arising from the mucosal surface. Most of the tumor
mass extends into the bile duct lumen. C, Photomicrograph showing the malignant cells largely
confined to the mucosa of the duct wall (arrow)
(hematoxylin-eosin stain, low power view).
198
HEPATOBILIARY CANCER
Table 9–2. CURRENT AMERICAN JOINT COMMISSION
ON CANCER STAGING SYSTEM FOR CANCER OF
EXTRAHEPATIC BILE DUCTS
Stage
Tumor
Node
Metastasis
0
1
2
3
4A
4B
Tis
T1
T2
T1 or 2
T3
Any T
N0
N0
N0
N1 or 2
Any N
Any N
M0
M0
M0
M0
M0
M1
Tis = carcinoma in situ; T1 = tumor invades subepithelial connective tissue or
fibromuscular layer; T2 = tumor invades perifibromuscular connective tissue;
T3 = tumor invades adjacent organs (liver, pancreas, duodenum, gallbladder,
colon, stomach).
N0 = no regional lymph node metastases; N1 = metastasis to lymph nodes
within the hepatoduodenal ligament (cystic duct, pericholedochal, and/or
hilar lymph nodes); N2 = metastasis to peripancreatic, periduodenal,
periportal, celiac, superior mesenteric, and/or posterior pancreaticoduodenal
lymph nodes.
M0 = no distant metastasis; M1 = distant metastasis.
can be achieved.14 In the AJCC system, patients with
involvement of N1- and N2-lymph nodes are staged
similarly. This is inappropriate since patients with
metastatic disease to N2-level lymph nodes (celiac,
periduodenal, or retroperitoneal) are not candidates
for resection and should be considered to have M1
disease. The Bismuth-Corlette system is more clinically relevant but is too simplified and, like the
AJCC system, correlates poorly with resectability
and survival.14 None of the current staging systems
takes into account local factors such as vascular
invasion or hepatic lobar atrophy, which are important determinants of resectability, which (in turn) is
a major determinant of outcome. A more reliable
and systematic method of selecting candidates for
resection is clearly needed (see below).
DIAGNOSIS
Symptoms and Physical Examination
The early symptoms of hilar cholangiocarcinoma
are nonspecific. Abdominal pain or discomfort,
anorexia, weight loss, and pruritus are the most
common symptoms and are seen only in one-third of
patients.3,11,13,24 Most of these tumors come to attention because of jaundice or abnormal liver function
tests. Jaundice is not present initially in cases of
incomplete biliary obstruction (ie, right or left
hepatic duct) or segmental ductal obstruction.
Patients with papillary tumors of the hilus may have
a history of fluctuating jaundice, which may be the
result of loose tumor fragments intermittently
obstructing the bile duct. In patients with cholangiocarcinoma and no previous biliary intervention,
cholangitis is uncommon at initial presentation
despite a 30 percent incidence of bacterial contamination (bacterbilia).11,25
The physical findings are often nonspecific.
Jaundice will usually be obvious. The gallbladder is
usually decompressed and nonpalpable with hilar
obstruction; thus, a palpable gallbladder suggests a
more distal obstruction or an alternative diagnosis.
Patients with long-standing biliary obstruction
and/or portal vein involvement may have findings
consistent with portal hypertension.
Alternative Diagnoses
The vast majority of patients with proximal biliary
obstruction and jaundice have cholangiocarcinoma.
However, alternative diagnoses are possible and can
be expected in 10 to 15 percent of patients.26 Gallbladder carcinoma, Mirizzi syndrome, and idiopathic
benign focal stenosis (“malignant masquerade”) are
the most common conditions that may be mistaken
for cholangiocarcinoma. Over a 28-month period at
Memorial Sloan-Kettering Cancer Center, we evaluated 109 patients with obstruction involving the biliary
confluence consistent with hilar cholangiocarcinoma.
In 90 patients, this diagnosis was confirmed while
19 patients were found to have other conditions (9
with gallbladder cancer, 6 with malignant masquerade,
3 with neuroendocrine tumor of the bile duct, and 1
with Mirizzi syndrome).
Distinguishing gallbladder carcinoma from hilar
cholangiocarcinoma can be difficult. A thickened
and irregular gallbladder with infiltration into segment IV, selective involvement of the right portal
pedicle, and obstruction of the common hepatic duct
with occlusion of the cystic duct on endoscopic
cholangiography are all suggestive of gallbladder
carcinoma. Mirizzi syndrome is a benign condition
resulting from a large gallstone impacted in the neck
of the gallbladder (Fig. 9–6).21,27 Benign focal strictures (malignant masquerade) can occur at the
Hilar Cholangiocarcinoma
199
Figure 9–6. Endoscopic retrograde cholangiography (ERCP) and cross-sectional computed tomography (CT) scan images of a patient with
Mirizzi syndrome. Left, The ERCP shows a characteristic large gallstone (arrow) impacted in the neck of the gallbladder, causing obstruction
of the hepatic duct just below the biliary confluence. Right, The CT scan confirms the presence of a large gallstone (arrow). In most cases,
the diagnosis of Mirizzi syndrome is not as clear-cut since the stone is usually not visualized. (Reproduced with permission from Jarnagin WR,
Saldinger PF, Blumgart LH. Cancer of the bile ducts: the hepatic ducts and common bile duct. In: Blumgart LH, Fong Y, editors. Surgery of the
liver and biliary tract. 3rd ed. Edinburgh [UK]: Churchill Livingstone; 2000.)
hepatic duct confluence but are uncommon (Fig.
9–7).26,28,29 Relying on the results of percutaneous
needle biopsy or biliary brush cytology is dangerous
since they are often misleading and because one may
miss the opportunity to resect an early cancer.30,31 It
is often impossible to establish the diagnosis
unequivocally before operation, and this is indeed
unnecessary in nearly all cases since lesions at the
biliary confluence (including benign strictures) are
best assessed and treated at operation. We firmly
A
believe that in the absence of clear contraindications
(see below), exploration is indicated in all patients
with suspicious hilar lesions.
TREATMENT
Preoperative Evaluation
Evaluation of patients with hilar cholangiocarcinoma is principally an assessment of resectability,
B
Figure 9–7. A, Endoscopic cholangiogram in a patient with a benign focal stricture of the common hepatic duct (white arrowhead). The
smooth, tapered appearance of the stricture suggests a benign process but is by no means conclusive. The cystic duct is shown partially filled
(black arrowhead). B, Photomicrograph of the common hepatic duct in the same patient. The duct lumen is severely narrowed by the surrounding scar tissue (arrowhead) (hematoxylin-eosin stain, low power view).
200
HEPATOBILIARY CANCER
since resection is the only effective therapy. First and
foremost, the patient’s general health and fitness for
major surgery (possibly including partial hepatectomy) must be examined. The presence of significant comorbid conditions, chronic liver disease,
and/or portal hypertension generally precludes
resection. Patients with potentially resectable tumors
may develop biliary tract sepsis, often after intubation of the biliary tree. These patients require resuscitation and treatment of the infection before surgery
is undertaken.
The preoperative evaluation must address four
critical determinants of resectability: (1) tumor
extent within the biliary tree, (2) vascular invasion,
(3) hepatic lobar atrophy, and (4) metastatic disease.14 Tumors that extend into the second-order biliary radicles bilaterally are not amenable to resection with clear margins, but this is often difficult to
determine before operation. Likewise, the presence
of metastatic disease (to distant sites or N2-level
lymph nodes) is a contraindication to resection.
Lobar atrophy is an often overlooked but important
factor in assessing the resectability of these tumors32
(see below). Long-standing biliary obstruction may
cause moderate atrophy whereas concomitant portal
venous compromise induces rapid and severe atrophy of the involved segments. On cross-sectional
imaging, atrophy is characterized by a small and
often hypoperfused lobe, with crowding of the
dilated intrahepatic ducts14 (Fig. 9–8).
Radiographic Studies
High-quality radiographic studies are critical in
selecting patients for resection. In the past, computed
tomography (CT), percutaneous transhepatic cholangiography (PTC), and angiography were considered
the standard investigations. Currently, we rely almost
exclusively on magnetic resonance cholangiopancreatography (MRCP), and duplex ultrasonography
(US). These noninvasive studies provide the same
information regarding the extent of disease as the
aforementioned studies but with less risk.
Magnetic resonance cholangiopancreatography
has emerged as a powerful investigative tool, and
we prefer it to the more invasive endoscopic retrograde cholangiography (ERCP) or PTC. Several
studies have demonstrated the utility of MRCP in
evaluating patients with biliary obstruction.33–35 It
may identify the tumor and level of obstruction and
may also reveal obstructed and isolated ducts not
seen by PTC. It also provides information regarding the patency of hilar vascular structures, the
presence of nodal or distant metastases, and lobar
Figure 9–8. Left, Cross-sectional computed tomography image of a patient with cholangiocarcinoma involving the left hepatic duct. The left
lobe, clearly demarcated from the right, is shrunken and hypoperfused (arrows). The bile ducts, which appear black, are dilated and crowded.
Right, T1-weighted gadolinium-enhanced cross-sectional magnetic resonance image of a different patient with hilar cholangiocarcinoma involving the left hepatic duct. The left lobe is small, and the bile ducts (which appear black) are dilated and crowded. There is evidence of hypoperfusion of the left lobe, which appears darker. There is also evidence of hypoperfusion of the right posterior sector, which also appears darker
and is clearly demarcated from the well-perfused right anterior sector (arrowheads) but does not as yet show evidence of atrophy. These radiographic features suggest that the tumor involves the left hepatic duct and the left portal vein and is beginning to involve the right portal pedicle. (Reproduced with permission from Jarnagin WR, Saldinger PF, Blumgart LH. Cancer of the bile ducts: the hepatic ducts and common bile
duct. In: Blumgart LH, Fong Y, editors. Surgery of the liver and biliary tract. 3rd ed. Edinburgh [UK]: Churchill Livingstone; 2000.)
Hilar Cholangiocarcinoma
A
201
B
Figure 9–9. A, T1-weighted gadolinium-enhanced magnetic resonance image of a patient with hilar cholangiocarcinoma. In this image, the
bile ducts appear black. A hilar tumor (T) is seen, apparently adherent to or encasing the right portal vein branch (PV) (white arrowhead). The
tumor has occluded the right anterior sectoral branch of the portal vein, and the anterior sector appears atrophic (indicated by the black lines),
with crowded dilated ducts. Intrahepatic metastases are also noted (arrow). B, Cross-sectional magnetic resonance cholangiopancreatography image through the same area of the liver. Similar findings are shown in this image, in which the bile ducts appear white. The vascular findings seen on magnetic resonance imaging were confirmed on duplex ultrasonography. Biopsies of the main tumor and the intrahepatic metastases confirmed adenocarcinoma. (Reproduced with permission from Jarnagin WR, Saldinger PF, Blumgart LH. Cancer of the bile ducts: the
hepatic ducts and common bile duct. In: Blumgart LH, Fong Y, editors. Surgery of the liver and biliary tract. 3rd ed. Edinburgh [UK]: Churchill
Livingstone; 2000.)
atrophy (Figs. 9–9 and 9–10). Furthermore, unlike
direct cholangiography, MRCP does not require
biliary intubation. Potential infectious complications, which may increase operative morbidity, are
thus avoided.
Duplex US is a valuable study in patients with
hilar obstruction; in experienced hands, US rivals all
other modalities for assessing extent of disease and
vascular involvement36–38 (Fig. 9–11). In our practice, MRCP and duplex US have become the preferred investigations.
Despite improvements in radiologic techniques,
only 20 to 50 percent of patients submitted to exploration have tumors that can be resected.13,14,39 We
have therefore proposed a preoperative staging system aimed at improving patient selection.14 Based
on the radiographic interpretation of local tumor
Patient Selection
Distinguishing resectable from irresectable tumors
demands careful consideration of all available data.
Bilateral tumor extension to second-order intrahepatic biliary radicles and encasement or occlusion of
the main portal vein clearly preclude resection. On
the other hand, involvement of the right or left
branch of the portal vein does not necessarily preclude resection. In this situation, complete resection
will require ipsilateral partial hepatectomy, but this
would not be possible if the contralateral lobe is
atrophic or if the tumor extends to the contralateral
second-order biliary radicles. The detailed criteria of
irresectability are outlined in Table 9–3.
Figure 9–10. Cross-sectional magnetic resonance cholangiopancreatography image from a patient with hilar cholangiocarcinoma
extending into the left hepatic duct and with left lobe atrophy. The bile
ducts appear white. The left lobe is small, with dilated and crowded
ducts (short arrow). The principal caudate lobe duct, seen joining the
left hepatic duct, is also dilated (long arrow). (Reproduced with permission from Jarnagin WR, Saldinger PF, Blumgart LH. Cancer of
the bile ducts: the hepatic ducts and common bile duct. In: Blumgart
LH, Fong Y, editors. Surgery of the liver and biliary tract. 3rd ed. Edinburgh [UK]: Churchill Livingstone; 2000.)
202
HEPATOBILIARY CANCER
extent (T stage), this system analyzes resectability
and considers the following factors: extent of biliary
ductal involvement, portal venous involvement, and
lobar atrophy (Table 9–4). Analyzing our patient
data by using the proposed system, we found that
Figure 9–11. A, Duplex ultrasonography in
a patient with a hilar cholangiocarcinoma. The
tumor is clearly seen at the biliary confluence
just above the portal vein (arrow). The mass is
clearly in contact with the portal vein, but
there is no clear invasion or venous narrowing. A transtumoral stent is also visible.
(Reproduced with permission from Jarnagin
WR, Saldinger PF, Blumgart LH. Cancer of
the bile ducts: the hepatic ducts and common
bile duct. In: Blumgart LH, Fong Y, editors.
Surgery of the liver and biliary tract. 3rd ed.
Edinburgh [UK]: Churchill Livingstone; 2000.)
B, Traverse color Doppler sonogram of the biliary confluence shows a papillary cholangiocarcinoma (m) extending into both the right
anterior (a) and posterior (p) sectoral ducts
and the origin of the left duct (l). The adjacent
portal vein (v) is not involved and has normal
flow. (Reproduced with permission from Hann
LE, Fong Y, Shriver CD, et al. Malignant
hepatic hilar tumors: can ultrasonography be
used as an alternative to angiography with
CT arterial portagraphy for determination
of resectability? J Ultrasound Med 1996;15:
37–45.)
A
B
resectability and the need for partial hepatectomy
both increased progressively with increasing T stage
while 5-year survival was inversely related (Table
9–5). By contrast, there was no correlation between
these variables and AJCC stage. The proposed stag-
Hilar Cholangiocarcinoma
Table 9–3. CRITERIA OF IRRESECTABILITY IN PATIENTS
WITH HILAR CHOLANGIOCARCINOMA
Patient Factors
Medically unfit for operation
Cirrhosis/portal hypertension
Local Factors
Hepatic duct involvement up to secondary radicles bilaterally
Encasement or occlusion of the main portal vein proximal to
its bifurcation
Atrophy of one lobe, with encasement of contralateral portal
vein branch
Atrophy of one lobe, with contralateral involvement of
secondary biliary radicles
Distant Disease
Histologically proven metastases to N2 lymph nodes
Liver, lung, or peritoneal metastases
Reprinted from Burke E, et al. Hilar cholangiocarcinoma. Patterns of spread,
the importance of hepatic resection for curative operation, and a presurgical
clinical staging system. Ann Surg 1998;228:386 by permission of the publisher Lippincott Williams and Wilkins.
ing system does not consider the status of the perihepatic lymph nodes. Enlarged reactive lymph nodes
are common in these patients, particularly those who
have been subjected to biliary instrumentation
before referral. Moreover, resection is not unreason-
203
able even in the setting of metastatic disease to N1level nodes since these are routinely cleared with the
tumor. By contrast, metastasis to N2-level nodes
would preclude resection, and biopsies should be
performed on suspicious nodes in these areas to confirm the diagnosis.
Preoperative Biliary Decompression and Infection
In patients considered candidates for resection and
without evidence of cholangitis, preoperative biliary
decompression is unnecessary and may be harmful.
There is substantial evidence that preoperative biliary intubation does not improve outcome, and the
observed increase in perioperative complications
outweighs any potential benefit.25,40–44
Operation
The treatment goals in patients with hilar cholangiocarcinoma are resection with negative histologic
margins and the restoration of enterobiliary continu-
Table 9–4. PROPOSED PREOPERATIVE TUMOR STAGING OF HILAR CHOLANGIOCARCINOMA
Tumor
Stage
T1
T2
T3
T4
Ipsilateral Lobar
Atrophy
Biliary Involvement
Hilus and/or right or left hepatic duct
Hilus and/or right or left hepatic duct
Hilus and/or right or left hepatic duct
Secondary biliary radicles bilaterally
No
Yes
Yes/No
Yes/No
Ipsilateral Portal
Vein Involvement
Main Portal
Vein Involvement
No
No
Yes
Yes/No
No
No
No
Yes
T1 tumors are confined to the hilus with or without involvement of the right or left hepatic duct and are not associated with atrophy or portal vein involvement. T2
tumors are associated with ipsilateral lobar atrophy but not portal vein branch involvement. T3 tumors are characterized by ipsilateral portal venous branch
involvement and may or may not be associated with lobar atrophy. T4 tumors are defined as irresectable, based on tumor extension to secondary biliary radicles
bilaterally or encasement/occlusion of the main portal vein.
Adapted from Burke E, et al. Hilar cholangiocarcinoma. Patterns of spread, the importance of hepatic resection for curative operation, and a presurgical clinical
staging system. Ann Surg 1998;228:387 by permission of the publisher Lippincott Williams and Wilkins.
Table 9–5. RESECTABILITY, INCIDENCE OF PARTIAL HEPATECTOMY, AND 5-YEAR SURVIVAL, BY PROPOSED TUMOR STAGE
T Stage
1
2
3
4
Total
No. of Patients
40
7
32
8
87
No. Resected
19
3
8
0
30
(48%)
(43%)
(25%)
(35%)
No. Requiring Partial Hepatectomy*
11
3
8
0
22
(58%)
(100%)
(100%)
(73%)
5-Year Survival (%)†
20
29
16
0
17 (57)‡
T = tumor.
*The percentage requiring partial hepatectomy is the percentage of those resected within a particular stage grouping.
†
5-year survival is recorded as a percentage of all patients seen, irrespective of therapy.
‡
The 5-year survival of all resected patients.
Adapted from Burke E, et al. Hilar cholangiocarcinoma. Patterns of spread, the importance of hepatic resection for curative operation, and a presurgical clinical
staging system. Ann Surg 1998;228:390 by permission of the publisher Lippincott Williams and Wilkins.
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HEPATOBILIARY CANCER
ity. Hepatic transplantation is associated with a prohibitively high incidence of recurrence, which has
led many centers to abandon its routine use in this
disease.45 All patients should be evaluated for possible resection before any intervention. Ill-advised
attempts to place biliary stents, especially when not
indicated, may result in complications that delay
operation, and stent-associated infection and
inflammation may hinder further radiographic and
operative assessment.40,45,46If resection is clearly not
feasible, then transtumoral drainage or intrahepatic
enterobiliary bypass offers satisfactory palliation
(see below).
At operation, the objective should be the complete resection of the tumor, with negative histologic
margins. Partial hepatectomy is usually required to
achieve this goal. Several recent series show a strong
correlation between negative histologic margins and
the percentage of patients subjected to partial hepatectomy (Table 9–6).14,39,47–49 Additionally, tumors
that extend into the left hepatic duct usually involve
the principal caudate lobe ducts and require en bloc
caudate lobectomy (see Fig. 9–10).39,47–50
III and IV should be divided to expose the left
hepatic duct at the base of the umbilical fissure.
Lowering the hilar plate will expose the biliary
confluence. Palpation of the duct in this area will
give the surgeon a sense of the tumor extent. The
distal bile duct is transected and elevated upwards,
allowing inspection of the anterior wall of the portal vein for evidence of tumor invasion; a portion
of the distal duct should be sent for frozen-section
histology. Once it has been determined that resection is feasible and will leave behind a tumor-free
liver remnant with intact blood supply and biliary
drainage, the surgeon should then control and
divide the inflow blood supply to the lobe that is to
be removed. The contralateral hepatic duct above
the tumor should be divided likewise, and a portion should be sent for frozen-section histology.
The hepatic vein draining that portion of the liver
to be excised should be exposed and divided extrahepatically. The parenchymal transection should
now be pursued. Finally, enterobiliary reconstruction is completed, using a 70-cm Roux-en-Y loop
of jejunum.
Operative Technique
Results
The operation begins with a thorough exploration of
the abdomen. Contrary to popular belief, metastatic
disease is common in patients with hilar cholangiocarcinoma.14,47,51 Performing staging laparoscopy
before proceeding to open exploration may help
identify some patients with unresectable disease.
The details of resection are illustrated in Figures 9–12 to 9–16. The duodenum and liver are
mobilized, and the gallbladder is taken down. The
bridge of liver tissue that often connects segments
It must be stressed that with the approach outlined
above, long-term survival can be achieved with
an acceptable operative mortality.12–14,39,48,49,52–54
Patients resected with negative histologic margins
survive significantly longer than those with microscopically positive margins (Table 9–7).14,39,52 Over
the past 20 years, there has been a steady increase
in the use of hepatic resection in patients with hilar
cholangiocarcinoma, resulting in an increase in the
proportion of R0 resections (ie, resections with neg-
Table 9–6. CORRELATION BETWEEN PARTIAL HEPATECTOMY AND HISTOLOGIC MARGINS IN
PATIENTS WITH HILAR CHOLANGIOCARCINOMA: SUMMARY OF RECENT SERIES
Author
Cameron (1990)47
Hadjis (1990)39
Nimura (1990)49
Klempnauer (1997)48
Burke (1998)14
Period of Study (yr)
Resected (N)
Partial Hepatectomy (%)
Negative Margins (%)
15
8
10
25
6
39
27
55
147
30
20
60
98
79
73
15
56
83
79
83
Adapted from Burke E, et al. Hilar cholangiocarcinoma. Patterns of spread, the importance of hepatic resection for curative operation, and a presurgical clinical
staging system. Ann Surg 1998;228:390 by permission of the publisher Lippincott Williams and Wilkins.
Hilar Cholangiocarcinoma
Figure 9–12. Initial operative approach. The round ligament has
been divided and is held upwards, exposing the undersurface of the
liver. The hilar plate at the base of segment IV has been lowered,
exposing the tumor at the biliary confluence. The bridge of liver tissue
attaching segments III and IV has been divided; this provides greater
exposure of the left hepatic duct. The gallbladder has been taken
down, and the distal bile duct has been divided. (Reproduced with permission from Blumgart LH, Fong Y, editors. Surgery of the liver and biliary tract. Edinburgh [UK]: Churchill Livingstone; 1997 [CD-ROM].)
Figure 9–13. Upward traction on the divided bile duct and periductal lymphatic tissues exposes the underlying portal vein. Developing
the plane between the tumor and the portal vein is the only way to
assess vascular invasion. Provided that the vein is not involved, a
plane between the tumor and the portal vein can easily be developed. Once it has been determined that resection is feasible, the
right hepatic artery is divided and retracted upwards with the tumor.
The left hepatic artery is retracted laterally, away from the tumor.
(Reproduced with permission from Blumgart LH, Fong Y, editors.
Surgery of the liver and biliary tract. Edinburgh [UK]: Churchill Livingstone; 1997 [CD-ROM].)
205
Figure 9–14. The left hepatic duct is divided well beyond the
tumor, and a portion is sent for frozen-section analysis. Further dissection exposes the portal vein confluence, and the right branch is
divided. (Reproduced with permission from Blumgart LH, Fong Y,
editors. Surgery of the liver and biliary tract. Edinburgh [UK]:
Churchill Livingstone; 1997 [CD-ROM].)
Figure 9–15. The hepatic parenchyma is divided after extrahepatic control of the right hepatic vein has been achieved. We crush the
parenchyma with a Kelley clamp and control intrahepatic vessels
and ducts with clips and ties. The central venous pressure is closely
monitored and kept under 5 mm Hg until the liver has been divided.
(Reproduced with permission from Blumgart LH, Fong Y, editors.
Surgery of the liver and biliary tract. Edinburgh [UK]: Churchill Livingstone; 1997 [CD-ROM].)
206
HEPATOBILIARY CANCER
Palliation
The majority of patients with cholangiocarcinoma
have irresectable disease at presentation or at laparotomy. Palliative biliary decompression may be
accomplished surgically or by percutaneous transtumoral biliary stenting. Adequate drainage of hilar
tumors is more difficult to achieve endoscopically,
and this approach is associated with a higher failure
rate and greater complications.55 Most patients
found to have irresectable tumors at presentation are
submitted for percutaneous drainage whereas those
found to have irresectable disease at laparotomy may
be suitable for intrahepatic enterobiliary bypass.56
External biliary drainage catheters can often provide
relief of jaundice or itching. When left in place for
long periods of time, however, these catheters can be
a source of cholangitis and may require frequent
changing. In addition, tumor growth along the tube
tract can occur, which can sometimes result in a
painful mass in the subcutaneous tissues (Fig. 9–17).
Self-expandable biliary endoprostheses, such as
Wallstents, are permanent internal devices that avoid
many of the problems and complications associated
with external drainage catheters. These stents, while
an improvement, are prone to occlusion secondary
Figure 9–16. Biliary reconstruction is performed, using interrupted
absorbable sutures to a Roux-en-Y loop of jejunum. The enteroenterostomy is created at least 70 cm distal to the enterobiliary anastomosis. (Reproduced with permission from Blumgart LH, Fong Y,
editors. Surgery of the liver and biliary tract. Edinburgh [UK]:
Churchill Livingstone; 1997 [CD-ROM].)
ative histologic margins). This is illustrated by the
senior author’s personal series of 269 patients accumulated over a 20-year interval (Table 9–8).14,39,53
Table 9–7. INFLUENCE OF HISTOLOGIC MARGINS ON SURVIVAL AFTER RESECTION OF HILAR CHOLANGIOCARCINOMA
Study
R0
Resections
R1
Resections
12
91
25
15
27
5
Hadjis 199039
Pichlmayr 1996*
Burke 199814
R0
Median Survival (mo)
R1
Median Survival (mo)
Operative
Mortality (%)
p
25
13
22
7
10
7
.04
.01
.01
43
26
> 60
R0 = resection with negative histologic margin; R1 = resection with positive histologic margin; p = probability.
*Pichlmayr R, Lamesch P, Weimann A, et al. Surgical treatment of cholangiocellular carcinoma. World J Surg 1995;19:83–8.
Adapted from Burke E, et al. Hilar cholangiocarcinoma. Patterns of spread, the importance of hepatic resection for curative operation, and a presurgical clinical
staging system. Ann Surg 1998;228:391 by permission of the publisher Lippincott Williams and Wilkins.
Table 9–8. EXPERIENCE WITH 269 HILAR CHOLANGIOCARCINOMA PATIENTS OVER 20 YEARS
Results
Patients evaluated
Patients resected
Negative margin
Hepatectomies performed
Operative mortality (%)
Median survival (mo)
5-yr survival (%)
NR = not reported.
1977–1985 (Hadjis NS39)
1986–1990 (Baer HU53)
1991–1997 (Burke EC14)
131
27
15 (56%)
16 (60%)
7.4
25
22
48
21
14 (67%)
9 (43%)
5
36
NR
90
30
25 (83%)
22 (73%)
6
40
56
Hilar Cholangiocarcinoma
207
measure for tumors of the esophagus, colon, stomach, bronchus, bladder, and brain. Although promising as a means of providing biliary decompression
without stents or perhaps as a way of treating those
with microscopically involved bile duct margins,
photodynamic therapy clearly needs further scrutiny
before it is widely adopted.
Chemotherapy
Chemotherapy has not been shown to improve survival in patients with unresectable disease, and its
use in this setting is difficult to justify outside the
context of a clinical trial.
Figure 9–17. Computed tomography scan showing tumor growth
along a percutaneous tube tract (arrowhead), with a large subcutaneous tumor mass.
to growth of tumor into the interstices (Fig. 9–18).
Once this occurs, patients usually require permanent
external biliary catheters passed through the previously placed metallic stent.
It cannot be overemphasized that patients with
unresectable hilar cholangiocarcinoma have a limited life expectancy, and palliative procedures associated with significant morbidity and/or frequent readmissions to the hospital have a tremendous
negative impact on quality of life.
A
Palliative Radiation Therapy
Patients with irresectable locally advanced tumors
may be candidates for palliative radiation therapy. A
combination of external beam radiation and intraluminal iridium-192 delivered percutaneously is typically used. Several authors have demonstrated the
feasibility of this approach although improved survival compared with that achieved with biliary
decompression alone has not been documented in a
controlled study.47,57–59
B
Photodynamic Therapy
Ortner and colleagues reported their limited experience with photodynamic therapy in patients with
irresectable hilar cholangiocarcinoma.60 This
approach has been used successfully as a palliative
Figure 9–18. A, Photograph of a Wallstent removed at operation in
a patient with hilar cholangiocarcinoma. Notice the ingrowth of tissue
into the stent wall. B, Computed tomography scan of a patient with
recurrent cancer after resection. A Wallstent had been previously
placed to relieve a biliary obstruction (black arrowhead); it subsequently became occluded and caused biliary obstruction proximal to
the stent. The left hepatic duct (white arrowhead) is markedly dilated
as a result of the occluded stent within its lumen.
208
HEPATOBILIARY CANCER
REFERENCES
1. Carriaga MT, Henson DE. Liver, gallbladder, extrahepatic bile ducts, and pancreas. Cancer 1995;75:
171–90.
2. Broome U, Olsson R, Loof L, et al. Natural history and
prognostic factors in 305 Swedish patients with primary sclerosing cholangitis. Gut 1996;38:610–5.
3. Pitt HA, Dooley WC, Yeo CJ, Cameron JL. Malignancies of the biliary tree. Curr Probl Surg 1995;32:
1–90.
4. Hewitt PM, Krige JE, Bornman PC, Terblanche J.
Choledochal cysts in adults. Br J Surg 1995;82:
382–5.
5. Lipsett PA, Pitt HA, Colombani PM, et al. Choledochal
cyst disease. A changing pattern of presentation.
Ann Surg 1994;220:644–52.
6. O’Neill JA. Choledochal cyst. Curr Probl Surg 1992;
29:371–409.
7. Tanaka K, Ikoma A, Hamada N, et al. Biliary tract cancer accompanied by anomalous junction of pancreaticobiliary ductal system in adults. Am J Surg
1998;175:218–20.
8. Hakamada K, Sasaki M, Endoh M, et al. Late development of bile duct cancer after sphincteroplasty: a
ten- to twenty-two-year follow-up study. Surgery
1997;121:488–92.
9. Chu KM, Lo CM, Liu CL, Fan ST. Malignancy associated with hepatolithiasis. Hepatogastroenterology
1997;44:352–7.
10. Kubo S, Kinoshita H, Hirohashi K, Hamba H. Hepatolithiasis associated with cholangiocarcinoma.
World J Surg 1995;19:637–41.
11. Way LW. Biliary tract. In: Way LW, editor. Current surgical diagnosis and treatment. 10th ed. Norwalk:
Appleton and Lange; 1994. p. 537–66.
12. Nagorney DM, Donohue JH, Farnell MB, et al. Outcomes after curative resections of cholangiocarcinoma. Arch Surg 1993;128:871–9.
13. Nakeeb A, Pitt HA, Sohn TA, et al. Cholangiocarcinoma. A spectrum of intrahepatic, perihilar, and distal tumors. Ann Surg 1996;224:463–75.
14. Burke EC, Jarnagin WR, Hochwald SN, et al. Hilar
cholangiocarcinoma: patterns of spread, the importance of hepatic resection for curative operation,
and a presurgical clinical staging system. Ann Surg
1998;228:385–94.
15. Fong Y, Blumgart LH, Lin E, et al. Outcome of treatment for distal bile duct cancer. Br J Surg 1996;83:
1712–5.
16. Yeo CJ, Cameron JL, Sohn TA, et al. Six hundred fifty
consecutive pancreaticoduodenectomies in the
1990s: pathology, complications, and outcomes.
Ann Surg 1997;226:248–57.
17. Berdah SV, Delpero JR, Garcia S, et al. A western surgical experience of peripheral cholangiocarcinoma.
Br J Surg 1996;83:1517–21.
18. Chu KM, Lai EC, Al-Hadeedi S, et al. Intrahepatic
cholangiocarcinoma. World J Surg 1997;21:301–6.
19. Harrison LE, Fong Y, Klimstra DS, Zee SY, Blumgart
LH. Surgical treatment of 32 patients with peripheral intrahepatic cholangiocarcinoma. Br J Surg
1998;85:1068–1070.
20. Weinbren K, Mutum SS. Pathological aspects of
cholangiocarcinoma. J Pathol 1983;139:217–38.
21. Baer HU, Matthews JB, Schweizer WP, et al. Management of the Mirizzi syndrome and the surgical
implications of cholecystocholedochal fistula. Br J
Surg 1990;77:743–5.
22. Shimada H, Niimoto S, Matsuba A, et al. The infiltration of bile duct carcinoma along the bile duct wall.
Int Surg 1988;73:87–90.
23. Bismuth H, Corlette MB. Intrahepatic cholangioenteric
anastomosis in carcinoma of the hilus of the liver.
Surg Gynecol Obstet 1975;140:170–8.
24. Farley DR, Weaver AL, Nagorney DM. “Natural history” of unresected cholangiocarcinoma: patient
outcome after noncurative intervention. Mayo Clin
Proc 1995;70:425–9.
25. Hochwald SN, Burke EC, Jarnagin WR, et al. Preoperative biliary stenting is associated with increased
post-operative infectious complications in proximal
cholangiocarcinoma. Arch Surg 1999;134:261–6.
26. Wetter LA, Ring EJ, Pellegrini CA, Way LW. Differential diagnosis of sclerosing cholangiocarcinomas of
the common hepatic duct (Klatskin tumors). Am J
Surg 1991;161:57–63.
27. Cabooter M, Sas S, Laukens P. [Mirizzi syndrome].
Ned Tijdschr Geneesk 1990;134:708–11.
28. Hadjis NS, Collier NA, Blumgart LH. Malignant masquerade at the hilum of the liver. Br J Surg
1985;72:659–61.
29. Verbeek PC, van Leeuwen DJ, de Wit LT, et al. Benign
fibrosing disease at the hepatic confluence mimicking Klatskin tumors. Surgery 1992;112:866–71.
30. Rabinovitz M, Zajko AB, Hassanein T, et al. Diagnostic value of brush cytology in the diagnosis of bile
duct carcinoma: a study in 65 patients with bile duct
strictures. Hepatology 1990;12:747–52.
31. Ryan ME. Cytologic brushings of ductal lesions during
ERCP. Gastrointest Endosc 1991;37:139–42.
32. Hadjis NS, Blumgart LH. Role of liver atrophy, hepatic
resection and hepatocyte hyperplasia in the development of portal hypertension in biliary disease.
Gut 1987;28:1022–8.
33. Guthrie JA, Ward J, Robinson PJ. Hilar cholangiocarcinomas: T2-weighted spin-echo and gadoliniumenhanced FLASH MR imaging. Radiology 1996;
201:347–51.
Hilar Cholangiocarcinoma
34. Lee MG, Lee HJ, Kim MH, et al. Extrahepatic biliary
diseases: 3D MR cholangiopancreatography compared with endoscopic retrograde cholangiopancreatography. Radiology 1997;202:663–9.
35. Schwartz LH, Coakley FV, Sun Y, et al. Neoplastic
pancreaticobiliary duct obstruction: evaluation with
breath-hold MR cholangiopancreatography. AJR
Am J Roentgenol 1998;170:1491–5.
36. Hann LE, Greatrex KV, Bach AM, et al. Cholangiocarcinoma at the hepatic hilus: sonographic findings.
AJR Am J Roentgenol 1997;168:985–9.
37. Hann LE, Fong Y, Shriver CD, et al. Malignant hepatic
hilar tumors: can ultrasonography be used as an
alternative to angiography with CT arterial portography for determination of resectability? J Ultrasound Med 1996;15:37–45.
38. Bach AM, Hann LE, Brown KT, et al. Portal vein evaluation with US: comparison to angiography combined with CT arterial portography. Radiology
1996;201:149–54.
39. Hadjis NS, Blenkharn JI, Alexander N, et al. Outcome
of radical surgery in hilar cholangiocarcinoma.
Surgery 1990;107:597–604.
40. Karsten TM, Allema JH, Reinders M, et al. Preoperative biliary drainage, colonisation of bile and postoperative complications in patients with tumours of
the pancreatic head: a retrospective analysis of 241
consecutive patients. Eur J Surg 1996;162:881–8.
41. Heslin MJ, Brooks AD, Hochwald SN, et al. A preoperative biliary stent is associated with increased
complications after pancreatoduodenectomy. Arch
Surg 1998;133:149–54.
42. McPherson GA, Benjamin IS, Hodgson HJ, et al. Preoperative percutaneous transhepatic biliary drainage:
the results of a controlled trial. Br J Surg 1984;71:
371–5.
43. Pitt HA, Gomes AS, Lois JF, et al. Does preoperative percutaneous biliary drainage reduce operative risk or
increase hospital cost? Ann Surg 1985;201:545–53.
44. Sirinek KR, Levine BA. Percutaneous transhepatic
cholangiography and biliary decompression. Arch
Surg 1989;124:885–8.
45. Jeyarajah DR, Klintmalm GB. Is liver transplantation
indicated for cholangiocarcinoma? J Hepatobiliary
Pancreat Surg 1998;5:48–51.
46. Karsten TM, Davids PHP, van Gulik TM, et al. Effects
of biliary endoprostheses on the extrahepatic bile
ducts in relation to subsequent operation of the biliary tract. J Am Coll Surg 1994;178:343–52.
209
47. Cameron JL, Pitt HA, Zinner MJ, et al. Management of
proximal cholangiocarcinomas by surgical resection
and radiotherapy. Am J Surg 1990;159:91–8.
48. Klempnauer J, Ridder GJ, von Wasielewski R, et al.
Resectional surgery of hilar cholangiocarcinoma: a
multivariate analysis of prognostic factors. J Clin
Oncol 1997;15:947–54.
49. Nimura Y, Hayakawa N, Kamiya J, et al. Hepatic segmentectomy with caudate lobe resection for bile
duct carcinoma of the hepatic hilus. World J Surg
1990;14:535–44.
50. Mizumoto R, Suzuki H. Surgical anatomy of the
hepatic hilum with special reference to the caudate
lobe. World J Surg 1988;12:2–10.
51. Lai EC, Tompkins RK, Mann LL, Roslyn JJ. Proximal
bile duct cancer. Quality of survival. Ann Surg
1987;205:111–8.
52. Pichlmayr R, Weimann A, Klempnauer J, et al. Surgical treatment in proximal bile duct cancer. A singlecenter experience. Ann Surg 1996;224:628–38.
53. Baer HU, Stain SC, Dennison AR, et al. Improvements
in survival by aggressive resections of hilar cholangiocarcinoma. Ann Surg 1993;217:20–7.
54. Parc Y, Frileux P, Balladur P, et al. Surgical strategy for
the management of hilar bile duct cancer. Br J Surg
1997;84:1675–9.
55. Cheung KL, Lai EC. Endoscopic stenting for malignant biliary obstruction. Arch Surg 1995;130:
204–7.
56. Jarnagin WR, Burke EC, Powers C, et al. Intrahepatic
biliary enteric bypass provides effective palliation
in selected patients with malignant obstruction at
the hepatic duct confluence. Am J Surg 1998;
175:453–60.
57. Bowling TE, Galbraith SM, Hatfield AR, et al. A retrospective comparison of endoscopic stenting alone
with stenting and radiotherapy in non-resectable
cholangiocarcinoma. Gut 1996;39:852–5.
58. Kuvshinoff BW, Armstrong JG, Fong Y, et al. Palliation
of irresectable hilar cholangiocarcinoma with biliary drainage and radiotherapy. Br J Surg 1995;
82:1522–5.
59. Vallis KA, Benjamin IS, Munro AJ, et al. External
beam and intraluminal radiotherapy for locally
advanced bile duct cancer: role and tolerability.
Radiother Oncol 1996;41:61–6.
60. Ortner MA, Liebetruth J, Schreiber S, et al. Photodynamic therapy of nonresectable cholangiocarcinoma. Gastroenterology 1998;114:536–42.