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Chapter 26 / Choledochal Cyst 331
Babbitt DP. Congenital choledochal cysts: new etiological concept based on anoma-
lous relationships of the common bile duct and pancreatic bulb. Ann Radiol
1969;12:231–240.
Dhupar R, Gulack B, Geller DA, et al. e changing presentation of choledochal cyst
disease: an incidental diagnosis. HPB Surg 2009;2009:103739.
Edil BH, Cameron JL, Reddy S, et al. Choledochal cyst disease in children and adults:
a 30-year single-institution experience. J Am Coll Surg 2008;206(5):1000–1005;
discussion 1005–1008.
Edil BH, Olino K, Cameron JL. e current management of choledochal cysts. Adv
Surg 2009;43:221–232.
Lipsett PA, Pitt HA. Surgical treatment of choledochal cysts. J Hepatobiliary Pancreat
Surg 2003;10(5):352–359.
Metcalfe MS, Wemyss-Holden SA, Maddern GJ. Management dilemmas with chole-
dochal cysts. Arch Surg 2003, 138(3): 333–339.
Singham J, Yoshida EM, Scudamore CH. Choledochal cysts: part 1 of 3: classication
and pathogenesis. Can J Surg 2009;52(5):434–440.
Singham J, Yoshida EM, Scudamore CH. Choledochal cysts: part 2 of 3: Diagnosis. Can
J Surg 2009;52(6):506–511.
Singham J, Yoshida EM, Scudamore CH. Choledochal cysts. Part 3 of 3: management.
Can J Surg 2010;53(1):51–56.
Todani T, Watanabe Y, Narusue M, et al. Congenital bile duct cysts: classication,
operative procedures, and review of thirty-seven cases including cancer arising
from choledochal cyst. Am J Surg 1977;134:263–269.
Ziegler KM, Pitt HA, Zyromski NJ et al. Choledochoceles: are they choledochal cyst?
Ann Surg 2010, 252(4): 683–690.
332
Cancers arising from the gallbladder and biliary tree are uncommon and
often present with advanced, incurable stages. e lack of eective systemic
and targeted therapies against these cancers has also added to the medical
nihilism associated with biliary malignancy in general. Most histopatho-
logic subtypes of adenocarcinoma along the biliary tract (e.g., gallbladder,
extrahepatic [distal, perihilar], intrahepatic) carry inltrative biologic
behavior and long-term survival, even for individuals who undergo com-
plete, potentially curative operative resection is exceptionally uncommon.
In the United States, approximately 10,000 new cases of biliary tract
cancer are diagnosed each year, with the highest incidence among Native
American and Hispanic women. Adenocarcinoma of the gallbladder stands
as the most common malignancy of the biliary tree with an overall inci-
dence of 1.5 per 100,000. Similar to all biliary tract cancers, gallbladder
cancer incidence varies dramatically according to racial and geographic
groups. Worldwide, high incidences of gallbladder cancer are reported in
women living in India, Pakistan, Ecuador, and Chile.
Over the past three decades, the incidence of intrahepatic cholangio-
carcinoma has increased worldwide while the incidence of extrahepatic
bile duct cancers, excluding gallbladder cancer, has shown a downward
trend. Several explanations for these observations have been hypothesized
and include more accurate classication systems, improvements in diag-
nostic imaging, changes in etiologic factors, and greater health care access
for low socioeconomic groups.
ETIOLOGY
Although most patients with gallstones do not develop cancer, the most
common factor associated with gallbladder cancer is gallstones leading
to chronic cholecystitis. Past studies have reported that large gallstones
(i.e., 3 cm or larger) may carry a 10-fold relative risk of gallbladder cancer.
Calcication of the gallbladder wall (i.e., porcelain gallbladder) reecting
chronic inammation is also associated with malignancy. Historically, this
risk was reported to be as high as 50%, but more accurately is estimated at
less than 10%. Other chronic inammatory diseases of the biliary tract, for
example, anomalous pancreatobiliary junction, cholecystoenteric stula,
and typhoid bacillus, are associated with gallbladder cancer and biliary
malignancy in general. While chronic inammation is one predisposing
factor for biliary malignancy, exposure to carcinogens (e.g., thorium, radon,
dioxin, nitrosamines, vinyl chloride, isoniazid, and asbestos) and bile com-
position rich in free radicals may further potentiate malignant transforma-
tion of the biliary epithelium.
Similar to other gastrointestinal cancers, gallbladder cancer seem-
ingly follows an adenoma to carcinoma sequence that reects specic
genetic mutation events. However, polypoid-type gallbladder cancers are
Biliary Malignancies
Michael G. House
27
Chapter 27 / Biliary Malignancies 333
extremely rare, and most patients with true multifocal polyps are not at
increased risk for cancer development. Cholecystectomy is recommended
for patients with true adenomatous polyps as the cancer incidence of mal-
ingancy among cholecystectomy specimens harboring polyps greater than
1 cm has been reported to be as high as 10%.
e most common risk factor associated with bile duct cancer in the
United States is primary sclerosing cholangitis (PSC). e natural history of
PSC varies, and the true incidence of cholangiocarcinoma within this popu-
lation is dicult to calculate. An estimated 8% of PSC patients, diagnosed
for at least 5 years, eventually develop cholangiocarcinoma ; however, nearly
40% of liver explants at the time of transplantation contain occult bile duct
cancer. e risk of developing cholangiocarcinoma in patients with ulcer-
ative colitis-associated PSC is estimated at 30% at 20 years.
Congenital choledochal cysts are associated with an increased risk of
cholangiocarcinoma especially in individuals with an anomalous pancrea-
tobiliary junction as the risk of bile duct cancer may approach 15% in this
population and appears to be time dependent. Chronic inammation of
the bile ducts as a result of pancreatic juice reux is felt to be the etiologic
factor, and similar risk has been observed in patients who undergo biliary
sphincteroplasty or sphincterotomy. Outside of Caroli disease, biliary cyst-
adenocarcinoma arising from a chronic, untreated cystadenoma is rare.
e risk of developing bile duct cancer, especially intrahepatic, is
also increased in patients with underlying cirrhosis secondary to chronic
hepatitis B or C infection. is nding might possibly explain the increased
incidence of intrahepatic cholangiocarcinoma in Western populations over
the past two decades. Recurrent pyogenic cholangiohepatitis and hepatoli-
thiasis resulting from chronic portal phlebitis have been established as eti-
ologies for cholangiocarcinoma, predominantly intrahepatic, in Southeast
Asia. Biliary parasites, namely Clonorchis sinensis and Opisthorchis viverrini,
which are endemic in various regions of Asia, increase the risk for both
extra- and intrahepatic cholangiocarcinoma.
DIAGNOSIS
ree clinical situations for the diagnosis of gallbladder cancer exist: nal
pathology of a routine cholecystectomy specimen reveals an incidental
cancer, cancer is discovered incidentally at the time of cholecystectomy, or
gallbladder cancer is detected preoperatively. is latter situation is often
associated with an advanced stage of disease and should be suspected in
patients with right upper quadrant pain, weight loss, anorexia, and jaun-
dice. Except for advanced stages of gallbladder cancer, laboratory testing
of serum is not helpful for diagnosis. Serum CA 19-9 levels are sensitive but
not specic for gallbladder cancer. Since gallbladder cancer is often asymp-
tomatic in early stages, the majority of resected cases are diagnosed inci-
dentally with routine cholecystectomy.
In the modern era of readily available imaging techniques, for exam-
ple, ultrasound and computed tomography (CT), most patients diagnosed
with gallbladder cancer have preoperative imaging available. Early stages
of gallbladder cancer can be detected with dedicated ultrasound that may
help to delineate echogenic mucosa associated with carcinoma compared
to benign disease and the presence of modest hepatic parenchymal inva-
sion. Cross-sectional imaging, with either CT or MRI, is crucial during
the diagnostic and staging evaluation of suspected gallbladder cancer
preoperatively or for complete staging when the diagnosis is established
intra- or postoperatively. Both modalities provide excellent resolution for
determining the local extent of disease (hepatic, vascular, and adjacent
Section III / Biliary334
organ involvement) and the presence of local or regional lymphadenopathy.
Distant sites of metastasis are best detected with CT imaging, which may
be enhanced with positron emission tomography (PET) using uorodeoxy-
glucose (FDG).
e diagnosis of intrahepatic cholangiocarcinoma is typically estab-
lished when a hypovascular tumor is detected on CT or MRI. Histologic con-
rmation is not necessary unless resection is not an option for treatment
or the tumor carries atypical radiographic features. Hepatic metastasis
from a primary source from the gastrointestinal tract, breast, lung, kidney,
etc. can be excluded with upper and lower endoscopy and/or whole-body
PET-CT functional imaging. Complete staging to evaluate for intra- and
extrahepatic sites of metastasis (e.g., regional lymph nodes, peritoneum)
and major vascular invasion can be accomplished with contrast-enhanced
cross-
sectional imaging (CT or MRI).
e diagnosis of hilar and distal cholangiocarcinoma usually follows
targeted studies for the evaluation of obstructive jaundice or elevated liver
enzymes. Most patients are referred after having had some initial studies
done elsewhere, usually CT and some form of direct cholangiography, for
example, endoscopic retrograde cholangiopancreatography (ERCP). Just as
for gallbladder cancer, histologic conrmation of malignancy is not manda-
tory before planning operative treatment. In the absence of previous biliary
tract surgery, the nding of a focal stenotic lesion along the extrahepatic
biliary ducts combined with the appropriate clinical presentation (i.e.,
jaundice) is adequate for a presumptive diagnosis of hilar or distal cholan-
giocarcinoma depending on the level of stricture formation.
Distal bile duct tumors frequently are mistaken for adenocarcinoma
of the pancreatic head, the most common periampullary malignancy. ERCP
and (magnetic resonance cholangiopancreatography) MRCP are typically
used to evaluate periampullary tumors when the diagnosis is suspected. As is
true for hilar lesions, MRCP can provide images of the distal bile duct previ-
ously obtainable only with ERCP or percutaneous cholangiography. A dilated
extrahepatic bile duct terminating abruptly at its distal aspect without a con-
comitantly dilated pancreatic duct suggests a distal bile duct cancer.
Although most patients with hilar strictures and jaundice have
cholangiocarcinoma, alternative diagnoses are possible in up to 15% of
patients. e most common of these are gallbladder carcinoma, Mirizzi
syndrome, and benign focal strictures (e.g., lymphoplasmacytic sclerosing
pancreatitis/cholangitis, granulomatous disease, and PSC). e nding of a
smooth, tapered stricture on cholangiography suggests a benign stricture.
Diagnostic assessments based on the cholangiographic appearance of the
stricture are unreliable, and hilar cholangiocarcinoma must remain the
leading diagnosis until disproved denitively. Relying on the results of per-
cutaneous or endoscopic ultrasound needle biopsy or biliary brush cytol-
ogy is not recommended because these results can be misleading. Many
tumors express carcinoembryonic antigen (CEA) and carbohydrate antigen
19-9 (CA 19-9); however, serum levels of these markers, although elevated in
some patients, often have little diagnostic value. Similarly, elevations of CA
19-9 or CEA levels in intraductal bile are not reliable or accurate.
e diagnosis of malignancy in patients with bile duct strictures
can be challenging and depends on accurate interpretation of ERCP as
well as cross-sectional imaging ndings. ERCP, in particular, is a useful
tool for assessing biliary tract strictures as it permits visualization of the
biliary tree with the opportunity for therapeutic interventions (i.e., bili-
ary drainage) and collection of specimens for cyto- and histopathologic
evaluation. Biliary brushing cytology, although highly specic, has suf-
fered from low to moderate sensitivity (15% to 68%). As a result, adjunctive
Chapter 27 / Biliary Malignancies 335
diagnostic techniques including mutation analysis, DNA ploidy analysis,
and
uorescence in situ hybridization (FISH) have been studied clinically
and experimentally to improve tumor detection sensitivity. Two types of
chromosomal abnormalities are frequently identied with a clinical FISH
probe set, namely polysomy and trisomy 7. Polysomy has been dened as a
gain of two or more of the four probes in ≥5 cells. FISH is now considered
more sensitive than cytology for detecting biliary tract cancer.
In patients with a stricture of the extrahepatic bile duct and a clini-
cal presentation consistent with cholangiocarcinoma or gallbladder car-
cinoma, histologic conrmation of malignancy is generally unnecessary,
unless nonoperative therapy is planned. Endoscopic brushings of the bile
duct have an unacceptably low sensitivity, making a negative result virtually
useless. Excessive reliance on the results of endoscopic ultrasound-guided
ne needle aspiration or endoscopic brush biopsies serves only to delay
therapy.
e diagnosis of cancer in the setting of PSC can be dicult as a result
of chronic liver disease, diuse biliary strictures, and inammatory changes
of the biliary epithelium. New-onset jaundice, elevations of serum CA 19-9
level, clinical weight loss, dominant biliary stricture formation with or with-
out cytologic or aneuploidic changes of dysplasia, or a detectable mass on
cross-sectional imaging may signify carcinoma.
MANAGEMENT
Preoperative Staging
Radiographic studies are pivotal in selecting patients for resection of
bile duct cancers. In addition to providing accurate preoperative staging
information and anatomic delineation of local disease extent, cross-
sectional imaging allows for careful operative planning. CT is an impor-
tant study for evaluating patients with biliary obstruction. A high-quality
CT scan can provide valuable information regarding the level of obstruc-
tion, vascular involvement, and liver atrophy. Advances in CT technology
permits the acquisition of three distinct circulatory phases, consisting of
the arterial, early, and late venous phases, in the hilar and pancreatobili-
ary regions.
Patients with hilar cholangiocarcinoma are dicult to stage preop-
eratively. e modied Bismuth-Corlette classication straties patients
based on the extent of biliary duct involvement by tumor alone (Fig. 27.1).
Although useful for operative planning, it does not predict resectability or
survival. e American Joint Commission for Cancer (AJCC) TNM stage
system (Table 27.1) is based largely on pathologic criteria and has little
relevance for preoperative staging. A preoperative staging system should
predict operative resectability and survival accurately. Preoperative
assessments should include (1) the extent of tumor within the biliary tree,
(2) vascular involvement, and (3) lobar atrophy (Table 27.2). is clinical
staging scheme underscores the importance of considering portal vein
involvement and liver atrophy in relation to the extent of ductal cancer
spread. Ipsilateral involvement of vessels and bile ducts is usually ame-
nable to resection, whereas contralateral involvement is not. Unilateral
involvement of the hepatic artery is compatible with resection. Bilateral
involvement of the hepatic artery usually is associated with nonresect-
ability when the tumor is located mainly on the right. Hepatic arte-
rial reconstruction in order to accomplish a complete resection should
be reserved for highly select patients with potentially curable disease.
Similarly, main portal vein invasion, while not an absolute contraindica-
tion for resection of hilar cholangiocarcinoma, will preclude a complete
Section III / Biliary336
resection with long-term benet for the majority of patients. Unresectable
hilar cholangiocarcinoma has been considered for orthotopic liver trans-
plantation in highly selected patients with protocolized conditions and
treatments.
e role of uorodeoxyglucose positron emission tomography (FDG-
PET) in the preoperative staging of patients with carcinoma of the gallblad-
der or biliary tract is unclear. e putative benets of FDG-PET to identify
occult metastatic disease or advanced regional lymphadenopathy have been
dicult to realize in clinical practice that utilizes timely, high- resolution
cross-sectional imaging routinely.
Preoperative Planning
High-resolution MRI cholangiopancreatography and direct cholangi-
ography (e.g., ERCP or percutaneous cholangiography) provide impor-
tant anatomic information, including the location of the tumor and the
biliary extent of disease, both of which are crucial in operative planning.
High-quality cholangiograms are essential for accurately diagnosing the
extent and level of bile duct involvement. High-performance MRCP has
almost replaced endoscopic and percutaneous cholangiography as the
initial preoperative assessment of hilar cholangiocarcinoma. MRCP not
only identies the tumor and the level of biliary obstruction but also may
reveal obstructed and isolated ducts not appreciated at endoscopic or
Type I
Type II
Type III
AB
FIGURE 27.1 Bismuth-Corlette classication scheme of malignant biliary strictures.
Chapter 27 / Biliary Malignancies 337
percutaneous study (Fig. 27.2). MRCP also provides information regarding
the patency of hilar vascular structures, the presence of nodal or distant
metastases, and the presence of lobar atrophy. Ultrasound, albeit opera-
tor dependent, is another useful noninvasive study during the preoperative
planning process. When utilized by experienced centers, it often delineates
tumor extent accurately. Ultrasound not only shows the level of biliary duc-
tal obstruction but also can provide information regarding tumor exten-
sion within the bile duct and in the periductal tissues. Duplex ultrasound
Primary Tumor (pT)
pTX: Cannot be assessed
pT0: No evidence of primary tumor
pTis: Carcinoma in situ
pT1: Tumor conned to the bile duct, with
extension up to the muscle layer or brous
tissue
pT2a: Tumor invades beyond the wall of the bile
duct to surrounding adipose tissue
pT2b: Tumor invades adjacent hepatic parenchyma
pT3: Tumor invades unilateral branches of the
portal vein or hepatic artery
pT4: Tumor invades main portal vein or its
branches bilaterally; or the common
hepatic artery; or the second-order biliary
radicals bilaterally; or unilateral second-
order biliary radicals with contralateral
portal vein or hepatic artery involvement
Regional Lymph Nodes (pN)
pNX Cannot be assessed
pN0 No regional lymph node metastasis
pN1 Regional lymph node metastasis (including
nodes along the cystic duct, common bile
duct, hepatic artery, and portal vein)
pN2 Metastasis to periaortic, pericaval, superior
mesentery artery, and/or celiac artery
lymph nodes
Distant Metastasis (pM)
pMx Cannot be assessed
pM1 Distant metastases present
Stage Groupings
Stage 0 Tis N0 M0
Stage I T1 N0 M0
Stage II T2a or T2b N0 M0
Stage IIIA T3 N0 M0
Stage IIIB T1, T2, or T3 N1 M0
Stage IVA T4 N0 or N1 M0
Stage IVB Any T N2 M0 or M1
Any T Any N M1
From Cholangiocarcinoma. In: Edge SB, Byrd DR, Compton CC (eds.). AJCC Cancer Staging Manual,
7th ed. New York, NY: Springer, 2010, with permission.
TABLE
27.1
AJCC Staging System, Seventh Edition, for Hilar Bile Duct
Cancer
Section III / Biliary338
is rmly established as a highly accurate predictor of vascular involvement
and technical resectability.
ERCP, when performed skillfully, provides useful ductal detail and
can eectively drain functional liver segments prior to operative plan-
ning. Percutaneous cholangiography, while invasive, outlines the extent
of intrahepatic bile duct involvement and has been the preferred study in
the past for patients with hilar cholangiocarcinoma. Compared to endo-
biliary drainage, PTC may provide more reliable biliary drainage of the
functional liver remnant when major hepatectomy is planned along with
biliary resection. e benets of preoperative biliary drainage have been
dicult to prove, but most centers currently advocate for such interven-
tion prior to resection of the extrahepatic bile ducts along with major
hepatectomy.
e absolute indications for preoperative biliary drainage for jaun-
diced patients prior to pancreatoduodenectomy are not clear. Randomized
controlled trials fail to demonstrate an improvement in postoperative
outcomes for patients with periampullary cancers; however, most experts
continue to advocate for preoperative endobiliary drainage for patients
with deep jaundice, that is, serum total bilirubin greater than 15 mg/dL.
Preoperative ERC with endobiliary drainage is the preferred approach in
this situation.
For patients with hilar and intrahepatic cholangiocarcinoma who
will require major hepatectomy, three-dimensional CT oers the capacity
to generate volumetric models of the total liver, planned hepatic resection,
and functional remnant liver volume. Since patients subjected to resec-
tion of more than 70% of functional liver parenchyma have substantially
a higher risk of postoperative liver failure regardless of existing cholestatic
liver disease, routine preoperative volumetry may help to identify patients
who may be at considerable risk for postoperative hepatic failure and select
candidates for preoperative portal vein embolization. e purpose of portal
vein embolization is to increase the functional liver mass by inducing com-
pensatory hypertrophy in the future liver remnant with the ultimate goal
to minimize postoperative liver dysfunction that contributes to mortality
substantially.
Stage Criteria
T1 Tumor involving biliary conuence±unilateral extension to
2 biliary radicles
T2 Tumor involving biliary conuence±unilateral extension to
2 biliary radicles
and ipsilateral portal vein involvement±ipsilateral hepatic
lobar atrophy
T3 Tumor involving biliary conuence+bilateral extension to
2 biliary radicles
Or unilateral extension to 2 biliary radicles with contralateral
portal vein involvement
Or unilateral extension to 2 biliary radicles with contralateral
hepatic lobar atrophy
Or main or bilateral portal venous involvement
From Jarnagin WR, Fong Y, DeMatteo RP, et al. Staging, resectability, and outcome in 225 patients
with hilar cholangiocarcinoma. Ann Surg 2001;234:507–519, with permission.
TABLE
27.2
Preoperative Staging System for Hilar Cholangiocarcinoma
Chapter 27 / Biliary Malignancies 339
In right portal vein embolization, the volume of the left lobe increases
by 130 cm
3
on average within 2 weeks after embolization, and the esti-
mated resection volume decreases by an average of approximately 10%.
In the absence of randomized controlled trials, the indications for portal
vein embolization remain somewhat arbitrary, but many centers utilize
this technique preoperatively for patients undergoing extended right
FIGURE 27.2 Coronal (A) and axial (B) MRCP images of a patient with hilar cholangio-
carcinoma. The tumor involves the right and left hepatic ducts. The bile ducts in this study
appear white. Extreme atrophy of the left hemiliver is apparent.
Section III / Biliary340
hepatectomy in the presence of underlying liver disease. In recent years,
some centers have experimented with associating liver partition and portal
vein ligation for staged hepatectomy (ALPPS) as a perioperative technique
to induce rapid hypertrophy of the future liver remnant and avoid postop-
erative liver dysfunction.
OPERATIVE INDICATIONS AND THERAPY
Staging laparoscopy for biliary tract malignancy should be considered for
all patients with suspicious clinicopathologic ndings for metastatic dis-
ease (e.g., remarkable elevations of serum CA 19-9 level, extreme weight
loss, rapidly declining performance status, indeterminant nodules involving
the liver or peritoneum). With an overall yield of 30%, staging laparoscopy
should be utilized for all patients with gallbladder cancer and intrahepatic
cholangiocarcinoma involving the liver capsule. Since the detection rate for
occult metastases is stage dependent, most surgeons apply staging laparos-
copy selectively for patients with extrahepatic bile duct cancer.
For gallbladder cancer in general, operative resection is indicated for
patients with localized disease, that is, tumors limited to the gallbladder,
liver bed, and regional lymph nodes. Peritoneal dissemination, extensive
liver or bile duct (especially left hepatic duct) involvement, nodal metas-
tases beyond the hepatoduodenal ligament (i.e., N2 disease, Fig. 27.3), left
hepatic arter y or portal vein encasement, or pancreatoduodenal inltration
FIGURE 27.3 Regional lymph nodes associated with gallbladder cancer. The subhilar N1
level lymph nodes within the hepatoduodenal ligament are encircled. Lymph nodes out-
side of the circle (e.g., celiac, aortocaval, and mesenteric nodes) are considered N2 level.
(Figure borrowed from Lillemoe K, Jarnagin WR (eds.). Hepatobiliary and pancreatic surgery.
Philadelphia, PA: Lippincott Williams & Wilkins, 2013.)