Tumor location may be important in determining the extent of resection. If the tumor arises in the

gallbladder infundibulum, the CBD is often involved with tumor, either by direct extension or external

invasion of the hepatoduodenal ligament. In this case, an extended liver resection and removal of a

portion of the CBD should be performed. Reconstruction is then performed by Roux-en-Y

hepaticojejunostomy. Tumor arising in the fundus of the gallbladder, however, can be treated with

limited hepatic resection without excision of the CBD. Complete regional lymphadenectomy should be

performed, skeletonizing the CBD, hepatic artery, and portal vein. Short-term postoperative outcomes

following resection of gallbladder cancer have remained relatively stable over time, with postoperative

morbidity occurring in 30% to 40% of patients, and mortality occurring in <5% (Table 63-4).

Incidentally or Laparoscopically Discovered Gallbladder Cancer

Gallbladder cancer is often discovered during pathologic examination after cholecystectomy for

presumed benign disease. Because of the popularization of laparoscopic cholecystectomy in the past

decade, an increasing number of patients with gallbladder cancer are found incidentally. Patients with

T1b or greater tumors and no signs of distant disease should be offered exploration and further

resection to eradicate all diseases. In a series of 135 patients who underwent reexploration following

laparoscopic cholecystectomy, 61% of all and 36% of those with T1b primary tumors were found to

have residual disease.54 In this study, survival following reresection of residual locoregional disease was

extremely poor and was not different from that of patients with metastatic disease. Improved survival

has been demonstrated following reresection to achieve negative margins, however, especially in

patients with T2 or T3 disease.51,55,56 While laparoscopic port-site recurrence has been reported, it is

associated with peritoneal-based disease. Port-site excision at the time of reexploration is no longer

recommended as recent data have shown that it is not associated with decreased recurrence or improved

survival.57,58

Reresection after recent cholecystectomy is often technically challenging. Postoperative inflammation

in the right upper quadrant often hinders distinction of tumor from normal tissue. Bile spillage at the

time of the initial operation may result in carcinomatosis.59 Determination of ductal or nodal

involvement by tumor is always difficult at the time of reoperation. In addition, postoperative fibrosis

often encases the right hepatic artery, which crosses behind the bile duct in most patients. Because of

this, during a second operation for incidentally discovered gallbladder cancer, an extended right

hepatectomy along with excision of the extrahepatic biliary tree and portal lymphadenectomy is often

necessary. This resection allows adequate exposure for lymphadenectomy and greater confidence of a

negative margin on the bile duct, and also permits biliary reconstruction to only one side of the liver.

The disadvantage is that a large portion of normal liver parenchyma is sacrificed, and consequently,

transient postoperative liver dysfunction is common. Although it may be more difficult to curatively

resect disease in patients with incidentally discovered gallbladder cancer after laparoscopic

cholecystectomy, there is no difference in overall survival between patients with incidentally discovered

gallbladder cancer who are submitted to curative resection and those patients who undergo initial

curative resection.50

When a patient presents with T1a gallbladder cancer discovered after simple cholecystectomy, the

pathology should be reviewed to determine if the entire gallbladder has been removed and if the cystic

duct margin is clear of tumor. If the cystic duct margin is positive, the patient requires bile duct

excision. If all margins are negative, no further therapy is warranted. If the tumor is proved to be T1b

or greater, complete staging should be performed. In the absence of metastatic disease, patients should

be counseled regarding reexcision to attempt complete resection, chemotherapy with or without

radiation, or observation. Patients with a known or suspected early gallbladder carcinoma should be

referred to an experienced center where curative-intent resection can be performed at the initial

operation.

Adjuvant Therapy

Adjuvant therapy for gallbladder cancer remains a controversial and unproved consideration and is

rarely utilized.45 Very few randomized trials have been completed, and the conclusions that can be

drawn from them are limited given the small sample sizes. Given the relative rarity of these

malignancies in the United States, large-scale, randomized trials are feasible only in the context of a

multi-institutional or cooperative group setting.

In 2002, a randomized phase III trial of adjuvant chemotherapy with 5-fluorouracil and mitomycin C

versus surgery alone for patients with pancreaticobiliary malignancies having resection found that in the

1638

subset of patients with gallbladder cancer (n = 112), the 5-year survival rate was significantly better in

the adjuvant group (26%) versus the control group (14%).60 Similarly, the 5-year disease-free survival

rate was 20.3% versus 11.6%, clearly favoring the adjuvant therapy group. A recent review of the SEER

database also reported an association between adjuvant chemoradiation therapy and improved survival

in patients with locoregionally advanced disease.61 This finding prompted a multi center phase II trial of

adjuvant capecitabine and gemcitabine followed by concurrent capecitabine and radiation therapy for

patients with resected gallbladder cancer or extra hepatic cholagiocarcinoma. The results of this study

were published in 2015 and showed promising findings of 65% two-year survival.62 These studies

suggest that patients with gallbladder cancer with high risk for recurrence (T2 or greater, node-positive,

or margin-positive) should be considered for adjuvant treatment with systemic chemotherapy or

chemoradiation.

Table 63-4 Complications Postoperative Morbidity Following Resection of

Gallbladder Cancer Over Time in the United States56

Prognosis

The 5-year survival rate for all patients with gallbladder cancer is less than 5% in most series, with a

median survival of 6 months. This is primarily because most patients present with unresectable disease.

Of those patients undergoing resection, survival is dependent on depth of penetration and nodal status.

Nearly 100% survival is reported after simple cholecystectomy for T1a disease, whereas patients with

T2 and T3 tumors without nodal disease have a 5-year survival greater than 50%.14,15,40,52 Node

positivity is an ominous finding, with few series reporting 5-year survivors.

Follow-up after Resection for Gallbladder Cancer

The most common sites of recurrence after resection of gallbladder cancer include carcinomatosis,

intrahepatic metastases, or nodal recurrence in the retroperitoneum. For most tumors, local recurrence

is found synchronously with diffuse intra-abdominal spread. Therefore, surgical treatment of recurrence

has little potential for cure. The main goal of surgery after recurrence of resected gallbladder cancer is

to provide palliation of symptoms such as pruritus or cholangitis associated with jaundice, or bowel

obstruction associated with carcinomatosis. When jaundice or cholangitis is the presenting symptom of

possible recurrence, a nonsurgical palliative approach using percutaneous transhepatic cholangiogram

(PTC) and stenting is usually favored unless a benign postsurgical stricture is suspected. Because of the

rapid growth of tumor in patients with recurrence, the hospitalization and recovery time from a surgical

bypass is usually not justified for recurrences resulting in biliary obstruction.

The routine follow-up of a patient after resection of gallbladder cancer includes office visits every 3

months with physical examination and measurement of liver function tests, and cross-sectional imaging

every 3 to 6 months for the first 2 years. In patients who remain free of disease at 2 years, follow-up

should be continued on an individualized basis. Although CA19-9 may be elevated in patients with

gallbladder cancer, the sensitivity and specificity are poor and, thus, should not be used for screening

patients for recurrence.63 If recurrence is identified, systemic therapy with gemcitabine and cisplatin

should be considered as it has been shown to prolong survival in the setting of metastatic disease.64 For

patients who cannot tolerate this regimen, alternatives include single-agent gemcitabine or gemcitabine

plus capecitabine.65

Issues for the Future

Clearly, improving our ability to recognize early gallbladder cancer in high-risk geographic areas would

have an important impact on outcome in these patients. This will likely require implementation of

screening programs in high-risk areas, which could result in prophylactic cholecystectomy.66

1639

Additionally, standardization of minimum pathologic assessment of gallbladder specimens in high-risk

areas is important to allow for accurate diagnosis, staging, and treatment of patients.

Further studies on characterization of molecular aberrations in gallbladder cancer by next generation

sequencing and other technologies may lead to the discovery of targetable mutations and lead to the

development of novel therapies. Additionally, there is a theoretical role for neoadjuvant therapy for

patients with locoregionally advanced gallbladder cancer given their poor prognosis following surgery.

Clinical trials in this area are needed.

BILE DUCT CARCINOMA

Bile duct carcinomas may arise within the liver (intrahepatic cholangiocarcinoma [ICC] or peripheral

cholangiocarcinoma), at the liver hilum (hilar cholangiocarcinoma or Klatskin tumor), or in the

extrahepatic bile duct (extrahepatic cholangiocarcioma [ECC]). While all arise from the biliary

epithelium, the location of these tumors affects prognosis as well as the potential for curative resection.

Resection of biliary neoplasms, particularly hilar cholangiocarcinoma, often requires radical

resections and complex biliary reconstructions that should be performed only at high-volume,

experienced centers. There is also a role for surgery in palliation for these cancers by providing biliary

bypass for jaundiced patients with unresectable tumors. Because disease is often diagnosed late in the

course and because complex operative techniques are required for potentially curative resection, these

tumors represent one of the greatest challenges for definitive treatment. Adding to this is that there are

no proven effective options for adjuvant therapy.

INCIDENCE

The incidence of ICC in the United States is approximately 0.7/100,000 with a similar mortality. During

the last 30 years, it appears that both the incidence and mortality in the United States are increasing.64

The overall incidence of hilar cholangiocarcinoma, the most common type, is 1.0/100,000 per year in

the United States, although rates are higher in other geographic regions such as Israel and Japan.68

Recent population studies have noted a trend toward a relative increased incidence of ICC compared to

ECC.4,69,70 Using the Surveillance, Epidemiology and End Results-Medicare databases, Welzel et al.70

noted HCV infection, chronic nonalcoholic liver disease and obesity, and smoking being associated only

with ICC and not ECC, possibly explaining the divergent trends in incidence. Cholangiocarcinomas arise

slightly more often in males, with a male-to-female ratio of 1.3:1 and an average age of 50 to 70 years.

Known risk factors for cholangiocarcinoma include primary sclerosing cholangitis, ulcerative colitis,

choledochal cysts, and biliary tract infection, either with Clonorchis or in chronic typhoid carriers.71

Some industrial chemicals (e.g., nitrosamines, dioxin, asbestos, and polychlorinated biphenyls) have also

been implicated in the pathogenesis of cholangiocarcinoma. Although there has been some suggestion of

an increased risk of cholangiocarcinoma arising after transduodenal sphincteroplasty,72 it is difficult to

determine if this is caused by the surgical intervention or the underlying disease leading to

sphincteroplasty.

Pathology and Staging

More than 90% of these bile duct cancers are adenocarcinomas. They are morphologically described as

nodular, which is the most common, scirrhous, diffusely infiltrating, or papillary. Histologic subtypes

include acinar, ductular, trabecular, alveolar, and papillary. Papillary tumors have an improved

outcome. Much less common types of bile duct tumors include cystadenocarcinomas,

hemangioendotheliomas, and mucoepidermoid carcinomas.

STAGING

Table 63-5 American Joint Committee on Cancer, 7th Edition, Staging System for

Perihilar Bile Duct Carcinoma

1640

In patients with ICC, negative prognostic signs include vascular invasion, multiple tumors, and lymph

node metastases, but not tumor size.73 These tumors can be sclerotic, masslike, or cystic lesions.

Historically, ECCs have been classified according to their location in the upper (60%), middle (15% to

20%), or lower third (15% to 20%) of the bile duct. Middle-third lesions arise between the cystic duct

and the superior border of the duodenum. Lower-third lesions are found below the superior border of

the duodenum but above the ampulla. The problem with this classification is that the anatomic

landmarks are somewhat arbitrary and not clinically useful. Most mid–bile duct malignant obstructions

are caused by gallbladder cancer. A more useful classification is to divide these lesions into upper-half

or lower-half tumors, based on the location of the cystic duct as it enters the common duct (in the case

of normal anatomy). The usefulness of this classification scheme is that it allows the surgeon to

delineate whether a hepatic or pancreatic resection will be required for clearance of tumor. The AJCC

TNM staging system (seventh edition) for bile duct cancers is described in Tables 63-5 and 63-6.

Other staging systems have been created that attempt to incorporate clinically important indicators of

resectability for hilar cholangiocarcinoma that are defined preoperatively, including hepatic lobe

atrophy or portal vein involvement.74 With the increasing acceptance of major hepatic resection for

these tumors, this preoperative staging system attempts to define whether there is ipsilateral

involvement alone, because tumors with bilateral extension past the primary biliary radicles are not

resectable.

STAGING

Table 63-6 American Joint Committee on Cancer, 7th Edition, Staging System for

Distal Bile Duct Carcinoma

1641

Clinical Findings and Diagnosis

The presentation of patients with cholangiocarcinoma is variable. Patients with hilar or extrahepatic

tumors most commonly present with painless jaundice. Symptoms of mild right upper quadrant pain,

pruritus, anorexia, malaise, and weight loss may also be reported. Cholangitis is the presenting

symptom in 10% to 30% of patients. Some patients, particularly those with ICC may be asymptomatic

and have their tumors discovered incidentally or on evaluation for elevations of alkaline phosphatase

and gamma-glutamyl transferase. Many of these patients will present to the surgeon with a biopsy

showing adenocarcinoma without a known primary tumor. The standard evaluation in these patients

should include tumor markers to rule out an elevated carcinoembryonic antigen (CEA) or α-fetoprotein

(AFP); upper and lower endoscopy to evaluate for a gastrointestinal source; CT scan to assess for a

primary tumor in the gastrointestinal tract or pancreas; and, in women, a mammogram. If no site of

primary disease is found, in most patients, the diagnosis is ICC.

Various imaging tests are available to assess patients with cholangiocarcinoma. Abdominal ultrasound

is noninvasive, easily available, and inexpensive, and thus is commonly used as a first imaging

modality. It can establish the level of biliary obstruction and rule out other etiologies, such as

choledocholithiasis. On CT, cholangiocarcinomas most often appear as hypodense masses with irregular

margins on precontrast phase images, with peripheral rim enhancement on arterial phase, followed by

progressive hyperattenuation on venous and delayed phases.75 Intrahepatic lesions often exhibit

associated capsular retraction and segmental/lobar atrophy and ductal dilatation. Hilar and proximal

extrahepatic lesions demonstrate dilated intrahepatic biliary ducts with a normal, collapsed gallbladder,

and, depending on the level of the tumor, a nondilated or partially dilated extrahepatic biliary tree (Fig.

63-5). While conventional CT is useful for assessment for extrahepatic, metastatic disease and perihilar

adenopathy, high-resolution CT and/or MRI are required for accurate assessment of the tumor and for

determination of respectability (Figs. 63-6 and 63-7).75 Portal vein patency can be determined with

ultrasound, CT, or MRI. Particularly for hilar tumors, signs of hepatic lobar atrophy should be carefully

sought, because this indicates ipsilateral portal vein involvement by tumor. MRCP offers the potential

of evaluating parenchymal, vascular, biliary, and nodal involvement with a single noninvasive

examination.25,27,76

16

 

mesenteric artery nodes. Nodal disease in the porta hepatis often causes common bile duct (CBD)

obstruction and resultant jaundice, which is the first clinical symptom in 30% of patients. Jaundice may

also be caused by tumors arising in the infundibulum, which may spread directly to the cystic duct and

common hepatic duct. Although peritoneal metastases are frequent, distant extraperitoneal metastases

are not.

Limited information exists regarding the genetic changes in gallbladder cancer. Recently reported

gene abnormalities associated with gallbladder cancer include p53, K-ras, CDKN2 (9p21), FGFR, and PI3

kinase pathway aberrations.16–20 The finding that patients with an anomalous pancreaticobiliary

junction have a greater frequency of K-ras mutations has led investigators to believe that reflux of

pancreatic enzymes into the biliary tree may contribute to the development of cancer.16 Because of our

limited knowledge of the sequence of molecular changes, there are no known detectors of early disease

or of risk assessment. Clearly, this is an area that needs improvement, particularly in endemic areas.

The American Joint Committee on Cancer’s (AJCC) seventh edition of its tumor, node, metastasis

(TNM) staging system (Table 63-1) reflects prognostic characteristics of tumor depth, regional nodal

disease, and distant spread. The gallbladder differs histologically from the rest of the gastrointestinal

tract in that it lacks a muscularis mucosa and submucosa. The gallbladder wall is composed of (a) a

single layer of columnar cells, the mucosa, and lamina propria; (b) a fibromuscular layer; (c) a

perimuscular, subserosal layer containing lymphatics and neurovascular structures; and (d) a serosal

surface, except where the gallbladder is embedded in the liver. Because lymphatics are present in the

subserosal layer only, tumors invading less than the full thickness of the muscular layer have minimal

risk of nodal spread. Thus, disease invading into, but not through, the muscular layer of the gallbladder

is T1b disease (stage I), whereas invasion into the perimuscular connective tissue is T2 (stage II). Stage

III disease includes tumors that have perforated the serosa or have directly invaded the liver or other

surrounding structures (T3), which are clearly more advanced but still potentially resectable. Tumors

that invade the main portal vein, hepatic artery, or two or more extrahepatic organs/structures are

classified as T4 (stage IVA) and are typically unresectable. Lymph node metastasis to regional,

periportal nodes are N1 whereas those to more distant nodes outside of what would be included in a

standard resection (celiac, periaortic, and superior mesenteric nodes) are N2. N1 nodal metastasis is

classified as stage IIIB and N2 as stage IVB. In line with other pancreaticobiliary malignancies, the stage

III grouping refers to locally advanced disease and stage IV indicates metastatic disease.

Clinical Findings and Diagnosis

Most patients are found to have gallbladder cancer during workup or treatment of cholelithiasis or

choledocholithiasis. In patients with symptoms, abdominal pain consistent with biliary colic or acute

cholecystitis is most common. Patients also present with jaundice, weight loss, anorexia, or an increase

in abdominal girth secondary to ascites. Physical findings may include right upper quadrant tenderness

or a palpable mass, hepatomegaly, and ascites. Laboratory investigation, if abnormal, is most often

consistent with biliary obstruction. Because of its nonspecific presentation and the lack of reliable

screening tests, gallbladder cancer is not diagnosed preoperatively in more than half the cases.

Imaging evaluation often reveals a thickened gallbladder wall or a mass within or replacing the

gallbladder on ultrasound examination. Because polyps, asymmetric wall thickening from cholecystitis

(especially xanthogranulomatous type), and carcinoma can have an echogenicity similar to the

gallbladder wall, these lesions are often difficult to distinguish. This is even more difficult when

inflammation is present from gallstones. At times, ultrasound can visualize invasion of the liver,

adjacent adenopathy, and a dilated biliary tree. The ability of ultrasound to differentiate benign from

neoplastic disease is enhanced using endoscopic ultrasound, and may be more specific than computed

tomography (CT) or magnetic resonance imaging (MRI).21–23

A dynamic contrast-enhanced CT scan may identify a gallbladder mass or invasion into the liver

parenchyma or adjacent organs. The classic finding in a patient with gallbladder cancer is asymmetric

thickening of the gallbladder wall. Staging of gallbladder carcinoma using CT, however, is limited by

poor sensitivity in identifying nodal spread.24

In patients who are jaundiced, direct cholangiography may be useful to delineate the extent of biliary

involvement as well as to palliate symptoms of biliary obstruction. A mid–bile duct obstruction not

caused by gallstones is gallbladder cancer until proved otherwise (Fig. 63-2). More recently, with

improvements in MRI technology, diffusion-weighted imaging and magnetic resonance

cholangiopancreatography (MRCP) have evolved into a single, noninvasive imaging modality that

allows complete assessment of biliary, vascular, hepatic parenchymal, and nodal involvement, as well as

1633

involvement of adjacent organs (Fig. 63-3).25–27

STAGING

Table 63-1 American Joint Committee on Cancer, 7th Edition, Staging System for

Gallbladder Carcinoma

In patients who present with incidentally discovered gallbladder cancer following cholecystectomy,

staging should be performed with high-quality CT or MRI of the chest, abdomen, and pelvis. There is no

clear role for PET/CT in this setting.28

Surgery

5 It is clear that the only curative option in patients with gallbladder cancer is complete surgical

resection. It is essential for optimal patient care that patients with gallbladder cancer be recognized

before laparoscopic cholecystectomy is performed, because of the risk of bile spillage, with its potential

for subsequent carcinomatosis.29

Role of Staging Laparoscopy

Because a large percentage of patients with gallbladder cancer are found to have occult, unresectable

disease at the time of surgical exploration, several authors have investigated the use of initial staging

laparoscopy for this disease.30–33 Because gallbladder cancer has such a propensity to spread intraabdominally, this tumor is ideal for detection of intra-abdominal metastases with laparoscopy. This is

demonstrated by the fact that up to 50% of patients are found to have unresectable disease at the time

1634

of laparoscopy.34,35 Patients who are found to have unresectable disease at laparoscopy can begin other

forms of systemic therapy earlier and may undergo the procedure as an outpatient. Particularly because

patients with unresectable disease have a median survival of only 6 months, the impact on quality of

life, including decreased length of stay in the hospital, cannot be overemphasized.

Figure 63-2. Endoscopic retrograde cholangiopancreatogram obtained from a patient with gallbladder cancer. Mid–bile duct

obstruction (arrow) is caused by direct extension of tumor to the cystic and common hepatic duct.

Cholecystectomy With or Without Partial Hepatectomy

Gallbladder cancer, if not completely surgically removed, results in rapid local progression and death. In

a collected review of 5,836 patients with gallbladder cancer, the overall mean survival was between 2

and 5 months, whereas the 5-year survival was 4%.5 The 5-year survival of patients undergoing

resection with curative intent was 17%. Of the 2,115 patients with unresectable disease, only a single

survivor was found at 5 years. Although surgical resection represents the treatment of choice and the

only potentially curative therapy available, resection is possible in only 25% of patients at presentation

because of the advanced nature of the disease.5

Figure 63-3. T1-weighted magnetic resonance imaging scan of a patient with gallbladder cancer (small arrows) with extension into

the duodenum and the hepatic flexure of colon (large arrows).

There is little doubt that the results of treatment, as well as the scope of operation, are related to

depth of tumor penetration (Table 63-2). For tumors limited to the muscular layer of the gallbladder

1635

(T1), there is near-universal agreement that simple cholecystectomy is adequate.15,36–38 T1 tumors have

not yet invaded the subserosal layer, which contains lymphatics, and therefore lymphadenectomy is not

required. Attesting to the fact that early gallbladder carcinoma is completely curable, simple

cholecystectomy has resulted in 90% to 100% survival when early cancer is an incidental finding after

elective cholecystectomy.15,47

RESULTS

Table 63-2 Five-Year Survival After Resection for Gallbladder Cancer

RESULTS

Table 63-3 Results After Radical Resection for Gallbladder Cancer

Difficulty can arise at the time of surgery in evaluating polypoid lesions of the gallbladder as either

benign or early gallbladder cancer. Although it appears that frozen section diagnosis is fairly reliable in

distinguishing whether lesions are malignant or benign (95% accurate), the accuracy in correctly

assessing depth of invasion is only 70%.47 Thus, it may be difficult at the time of surgery to determine

the extent of resection. Because of this, pursuing a more aggressive resection if the depth of invasion is

in doubt is important for adequate tumor clearance.

The extent of surgical resection for T2 or greater tumors is controversial, with recommendations

ranging from simple cholecystectomy to radical excision, including hepatectomy. For advanced local

disease, some groups have advocated radical resections, including hepatectomy and pancreatectomy.

Whereas it is clear that major hepatic resection can be performed safely with a mortality less than 5%

(Table 63-3) it has not been universally accepted that more aggressive resections, such as combined

hepatectomy and pancreaticoduodenectomy, improve survival.14,15,36,37,40,48

To understand the rationale for extensive resections, it is also important to understand the pattern of

spread of gallbladder cancer. Direct extension to the adjacent liver parenchyma often occurs first,

followed by adjacent organ involvement, including duodenum, colon, and stomach (Fig. 63-2).

Lymphatic spread of gallbladder cancer is routine, often involving nodes in the porta hepatis,

peripancreatic region, celiac axis, and the aortocaval nodal basins. There is currently no consensus on

the extent of lymphadenectomy that is appropriate for gallbladder cancer. Extensive lymphadenectomy

1636

including para-aortic nodes is advocated in the East, but is not universally accepted. Recently, a

technique of intraoperative nodal staging was proposed that entails sampling the highest peripancreatic

lymph node for frozen section. This is the lymph node situated between the N1 and N2 nodal stations at

the junction of the bile duct and the superior border of the head of the pancreas (Fig. 63-4). Metastatic

disease to this node has been shown to be a poor prognostic factor.49

Figure 63-4. Illustration of the highest peripancreatic lymph node.

Because the gallbladder is not surrounded by serosa where it is attached to the liver in the gallbladder

fossa, even T2 tumors (full-thickness invasion of the muscular layer into the perimuscular connective

tissue, no extension beyond serosa or into liver) can invade the normal plane of dissection in the

gallbladder fossa during simple cholecystectomy. Therefore, T2 tumors cannot be completely removed

with cholecystectomy alone, and a radical cholecystectomy, with resection of a 1- to 2-cm rim of normal

liver around the gallbladder fossa, is the minimal resection that is required. Many authors, however,

have found that segmental resection of segments IVb and V of the liver, which abut the gallbladder

fossa, results in a more anatomically controlled dissection with less blood loss.50 An additional part of

the definitive surgical treatment is regional lymphadenectomy, because about half the patients with T2

tumors are found to have nodal spread after resection.14 Dissection of lymph nodes should include all

tissues from the bifurcation of the hepatic ducts to the distal CBD. Proponents of this approach advocate

liver resection on the basis that it is the only way to obtain an adequate margin on the hepatic side of

the gallbladder and resection of the regional nodes allows the best chance for complete tumor clearance.

For all of these reasons, simple cholecystectomy is inadequate for T2 or greater tumors. When larger

anatomic hepatic resections have been performed in patients with T2 tumors, it has increased the 5-year

survival from 25% to 40% after simple cholecystectomy to 70% to 100% after radical

resection.14,36–38,39,43,44,51,52

For T3 and T4 lesions, there is a high likelihood of intraperitoneal and hematogenous spread and

significant morbidity from the radical procedures that are often necessary for excision of local disease.

Recent series, however, support an aggressive approach to resection of these large tumors, particularly

if no indication of nodal involvement is found (Table 63-3). For T3 and resectable T4 tumors, a minimal

resection includes segments IVb and V, and in many cases an extended right hepatectomy (segments IV,

V, VI, VII, and VIII) may be necessary to obtain complete resection. With aggressive resection, longterm survival can be achieved even for patients with these more advanced tumors.14,15,36,37,40,53

Surgical exploration should be performed for all patients without medical contraindications. If a T1

tumor is suspected, a cholecystectomy and biopsy of regional nodes should be performed after thorough

examination of the abdominal cavity for any signs of tumor dissemination. The pathology and depth of

penetration should be confirmed by frozen section, and the procedure terminated if a T1 tumor with

negative margins is confirmed. For T2 lesions, either a radical cholecystectomy (wedge resection of the

hepatic bed) or a segment IVb and V resection with lymphadenectomy should be performed.14 For T3

lesions, a segment IVb and V resection or extended right hepatectomy is performed. Finally, for T4

lesions, a more radical excision of the liver, such as extended right hepatectomy, usually must be

performed for adequate tumor clearance.

1637

 

Figure 62-16. Cholangiogram of a patient with cholangiohepatitis with diffuse bile duct dilatation. The biliary tree is filled with

sludge (Sl) and stones.

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iatrogenic injuries: a nonadvisable approach. J Gastrointest Surg 2008;12:1029–1032.

16. Lillemoe KD. Treatment of laparoscopic bile duct injuries. Curr Tech Gen Surg 1997;6:1.

17. Warren KW, Christophi C, Armendari ZR. The evolution and current perspectives of the treatment

of benign bile duct strictures: a review. Surg Gastroenterol 1982;1:141.

18. Sicklick JK, Camp MS, Lillemoe KD, et al. Surgical management of bile duct injuries sustained

during laparoscopic cholecystectomy: perioperative results in 200 patients. Ann Surg 2005;241:786–

792; discussion 793–795.

19. Pitt HA, Kaufman SL, Coleman J, et al. Benign postoperative biliary strictures: operate or dilate?

Ann Surg 1989;210:417–425; discussion 426–427.

20. David PHP, Tanka AKF, Rauws EAJ, et al. Benign biliary strictures: surgery or endoscopy? Ann Surg

1993;217:237.

21. Lillemoe KD, Melton GB, Cameron JL, et al. Postoperative bile duct strictures: management and

outcome in the 1990s. Ann Surg 2000;232:430–441.

22. Walsh RM, Henderson JM, Voglt DP, et al. Long-term outcome of biliary reconstruction for bile

duct injuries from laparoscopic cholecystectomies. Surgery 2007;142:450–456; discussion 456–457.

23. Pitt HA, Sherman S, Johnson MS, et al. Improved outcomes of bile duct injuries in the 21st century.

Ann surg2013;258:490–499.

24. Stewart L, Way LW. Bile duct injuries during laparoscopic cholecystectomy. Arch Surg

1995;130:1123–1128; discussion 1129.

25. Murr MM, Gigot JI, Nagorney DM, et al. Long-term results of biliary reconstruction after

laparoscopic bile duct injuries. Arch Surg 1999;134:604–609; discussion 609–610.

26. Laurent A, Sanvanet A, Farges O, et al. Major hepatectomy for the treatment of complex bile duct

injury. Ann Surg 2008;248:77–83.

27. de Santibanes E, Ardilles V, Gadano A, et al. Liver transplantation: the last measure in the

treatment of bile duct injuries. World J Surg 2008;32:1714–1721.

28. Flum DR, Cheadle A, Prela C, et al. Bild duct injury during cholecystectomy and survival in

Medicare beneficiaries. JAMA 2003;290:2168–2173.

29. Melton GB, Lillemoe KD, Cameron JL, et al. Major bile duct injuries associated with laparoscopic

cholecystectomy: effect on quality of life. Ann Surg 2002;235:888–895.

30. Horgan AM, Hoti E, Winter DC, et al. Quality of life after iatrogenic bile duct injury: a case control

study. Ann Surg 2009;249:292–295.

31. Ejaz A, Spolverato G, Kim Y, et al. Long-term health-related quality of life after iatrogenic bile duct

injury repair. J Am Coll Surg 2014;219:923–932 e10.

32. Mueller PR, van Sonnenberg E, Ferrucci JT Jr, et al. Biliary stricture dilatation: multicenter review

of clinical management in 73 patients. Radiology 1986;160:17–22.

33. Misra S, Melton GB, Geschwind JF, et al. Percutaneous management of bile duct strictures and

injuries associated with laparoscopic cholecystectomy: a decade of experience. J Am Coll Surg

2004;198:218–226.

34. de Reuver P, Rauws EA, Vermenlen M, et al. Endoscopic treatment of post-surgical bile duct

injuries: long term outcomes and predictors of success. Gut 2007;56:1599–1605.

35. Geenen DJ, Geenen JE, Hogan WJ, et al. Endoscopic therapy for benign bile duct strictures.

Gastrointest Endosc 1989;35:367–371.

36. Lindor KD. Ursodiol for primary sclerosing cholangitis. Mayo Primary Sclerosing CholangitisUrsodeoxycholic Acid Study Group. N Engl J Med 1997;336:691–695.

37. Gluck M, Cantone NR, Brandabur JJ, et al. A 20-year experience with endoscopic therapy for

primary sclerosing cholangitis. J Clin Gastroenterol 2008;42:1032–1039.

38. Pawlik TM, Olbrecht VA, Pitt HA, et al. Primary sclerosing cholangitis: role of extrahepatic biliary

resection. J Am Coll Surg 2008;206:822–830; discussion 830–832.

39. Gross JA, Shackelton CR, Farmer DG, et al. Orthotopic liver transplantation for primary sclerosing

cholangitis: a 12-year single center experience. Ann Surg 1997;225:472–481; discussion 481–483.

40. Stahl TJ, Allen MO, Ansel M, et al. Partial biliary obstruction caused by chronic pancreatitis: an

appraisal of indications for surgical biliary drainage. Ann Surg 1988;207:26–32.

41. Warshaw AL, Schapiro RH, Ferrucci JT Jr, et al. Persistent obstructive jaundice, cholangitis, and

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biliary cirrhosis due to common bile duct stenosis in chronic pancreatitis. Gastroenterology

1976;70:562–567.

42. Afroudakis A, Kaplowitz N. Liver histopathology in chronic bile duct stenosis due to chronic

alcoholic pancreatitis. Hepatology 1981;1:65–72.

43. Chari ST, Smyrk TC, Levy MJ, et al. Diagnosis of autoimmune pancreatitis: the Mayo Clinic

experience. Clin Gastro Hepta 2006;4:1010–1016; quiz 934.

44. Beltran MA. Mirizzi syndrome: history, current knowledge and proposal of a simplified

classification. World J Gastroenterol 2012;18:4639–4650.

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Chapter 63

Biliary Neoplasms

Kaitlyn J. Kelly, Yuman Fong, and Sharon Weber

Key Points

1 Surgery remains the only curative option for biliary malignancies.

2 Gallbladder cancer is a rare malignancy with a dismal prognosis because of its insidious onset,

propensity for local invasion, and rapid disease progression.

3 The association of gallstones with carcinoma is probably related to chronic inflammation.

4 Patients with choledochal cysts have an increased risk of carcinoma developing anywhere in the

biliary tree, but the incidence is highest in the gallbladder.

5 The only curative option in patients with gallbladder cancer is complete surgical resection.

6 Nonoperative palliative biliary decompression can be accomplished with percutaneous or endoscopic

stenting, depending on the level of obstruction.

INTRODUCTION

1 Tumors arising in the gallbladder and biliary tree are rare, with approximately 10,650 cases per year

in the United States and 140,000 per year worldwide.1,2 These tumors are often asymptomatic until late

in the course of the disease. Consequently, these tumors commonly present in an advanced, often

unresectable stage. Surgery remains the only curative option for biliary malignancies. Complete

resection of biliary neoplasms, however, often requires radical resections and complex biliary

reconstructions that are only routinely safe at specialized, high-volume centers. Surgery also offers

potential for effective palliation of these cancers, including biliary bypasses for jaundiced patients with

unresectable tumors. Both the late diagnosis and the complex operative techniques required for

potentially curative resection contribute to the challenge of these cases. In addition, there are no proven

effective options for adjuvant treatment. This chapter reviews the incidence, diagnosis, and therapy of

these malignancies as well as the outcomes of treatment.

GALLBLADDER CARCINOMA

2 Gallbladder cancer is a rare malignancy with a dismal prognosis because of its insidious onset,

propensity for local invasion, and rapid disease progression. Overall, most series report a 5-year

survival of less than 5%.

Incidence

Gallbladder cancer is the most common biliary tract malignancy, but there are only 6,000 to 7,000 new

cases diagnosed nationally each year. Attesting to the rarity of this lesion, after routine screening of

abdominal ultrasounds in asymptomatic patients in Japan, only 19 out of 194,767 patients (0.01%) were

found to have gallbladder cancer.3 This tumor occurs more frequently in women (female:male ratio =

3:1), and peak incidence is in the seventh decade.4 There is a tremendously increased risk of gallbladder

cancer, in particular indigenous populations, including Mapuche Indians in South America (12.3

cases/100,000 males and 27.3/100,000 females, and Native Americans in New Mexico (8.9

cases/100,000 people).5,6

The increased risk of gallbladder cancer with cholelithiasis is well established; 70% to 90% of all

patients with carcinoma also have gallstones. However, less than 0.5% of patients with gallstones are

found to have gallbladder cancer.5 In recent series of patients undergoing elective cholecystectomy for

gallstones, gallbladder cancer is found incidentally in <0.5% of patients.7 The association of gallstones

with carcinoma is probably related to chronic inflammation. Larger stones (>3 cm) are associated with

1631

a 10-fold increased risk of cancer.6,8

3 The association of gallbladder cancer with gallstone disease has led some investigators to question

whether all patients with gallstones should undergo cholecystectomy. The argument against this

approach is that the use of cholecystectomy only for symptomatic patients, thus leaving the gallbladder

in place in patients with asymptomatic gallstones, has not led to an increase in the prevalence of

gallbladder cancer over time. Also, epidemiologic studies have found that the 20-year risk of developing

cancer in patients with gallstones is less than 0.5% for the overall population and 1.5% for high-risk

groups.5 Thus, routine cholecystectomy for asymptomatic gallstones because of concern for gallbladder

cancer does not appear to be warranted.

In the past, the finding of a calcified gallbladder wall, called “porcelain gallbladder” (Fig. 63-1), was

associated with a high risk of cancer, in some series ranging from 25% to 60%.9 Thus, the

recommendation was for all patients with porcelain gallbladder to undergo open cholecystectomy, even

if asymptomatic. Recent series evaluating this issue, however, suggest that the risk of gallbladder cancer

in patients with porcelain gallbladder has likely been greatly overestimated. In fact, although patients

with limited areas of calcification of the wall may have a higher incidence of gallbladder cancer (7%),

patients with diffuse calcification of the gallbladder wall, the classic presentation for porcelain

gallbladder, do not appear to have an increased risk of gallbladder cancer.10,11

4 Patients with choledochal cysts have an increased risk of carcinoma developing anywhere in the

biliary tree, but the incidence is highest in the gallbladder. This risk increases with age. Therefore,

cholecystectomy is recommended for all patients with choledochal cysts at the time of diagnosis.

Figure 63-1. Unresectable gallbladder cancer demonstrating palliative transhepatic percutaneous stent placed to relieve jaundice.

Porcelain gallbladder is present (arrows).

Pathology and Staging

More than 80% of gallbladder cancers are adenocarcinomas; there are several histologic subtypes,

including papillary, nodular, and tubular. Papillary tumors, which grow predominantly into the

gallbladder lumen, have an improved prognosis compared with the other subtypes.12 Poor prognostic

signs in gallbladder cancer include grade, and vascular invasion.12,13 The most important prognostic

factor may be lymph node status, although 5-year survivors with nodal involvement have been

documented.14,15 Less than 5% of cases are squamous cell carcinomas, with the remaining 10% being

anaplastic lesions.

Gallbladder cancer spreads via the lymphatic and venous drainage. Because of drainage of the

cholecystic veins directly into the adjacent liver, these tumors often involve hepatic parenchyma, most

often portions of segments IV and V. Lymphatic spread is first to the cystic duct (Calot) node, then to

pericholedochal and hilar nodes, and finally to peripancreatic, duodenal, periportal, celiac, and superior

1632

 

pancreatitis must be differentiated from underlying periampullary malignancy.

Figure 62-14. Actuarial survival rates among 31 noncirrhotic patients with primary sclerosing cholangitis who underwent resection

of the hepatic bifurcation and long-term transhepatic stenting. (Reproduced with permission from Lillemoe KD, Pitt HA, Cameron

JL. Primary sclerosing cholangitis. Surg Clin North Am 1990;70:1381–1402.)

The definitive evaluation of patients with a bile duct stricture caused by chronic pancreatitis is

cholangiography. Either MRCP or ERCP is the preferred diagnostic procedure as they both can

demonstrate both biliary and pancreatic ductal anatomy, which is essential in optimal surgical

management of chronic pancreatitis. ERCP with stenting allows decompression of the obstructed biliary

tree if necessary for cholangitis or severe jaundice. A long (usually 2- to 4-cm), smooth, gradual

tapering of the common bile duct is most compatible with a benign stricture due to chronic pancreatitis

(Fig. 62-15).

The indications for surgical management of common bile duct strictures due to chronic pancreatitis

are clear in patients with significant pain, jaundice, or cholangitis. Controversy exists, however,

concerning the necessity of biliary decompression in patients with an asymptomatic elevation of serum

alkaline phosphatase. In general, biliary bypass is indicated because changes from obstructive biliary

cirrhosis have been observed in liver biopsy specimens obtained from patients with long-standing,

functionally significant biliary obstruction due to chronic pancreatitis.41,42 Some clinicians may also

consider biliary dilatation and temporary intraluminal stenting in this setting using either endoscopic

(preferred) or percutaneous approaches.

Choledochoduodenostomy and Roux-en-Y choledochojejunostomy are acceptable methods of biliary

bypass in patients with bile duct strictures caused by chronic pancreatitis. Choledochoduodenostomy is

preferred by many surgeons because it does not divert bile from the duodenum, is technically easier to

perform, and leaves the jejunum intact for any associated procedures required for decompression of an

obstructed gastrointestinal tract or pancreatic duct. Finally, in patients in whom periampullary

malignancy cannot be completely ruled out by the clinical course or imaging studies, or in patients with

significant chronic pain thought secondary to proximal pancreatic duct disease,

pancreaticoduodenectomy offers an excellent treatment option. The results of surgical management of

distal bile duct structures due to chronic pancreatitis are usually excellent, with a low rate of

perioperative complications and excellent long-term results.

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Figure 62-15. Cholangiogram of a patient with a long distal common bile duct stricture (arrow) caused by chronic pancreatitis.

Transduodenal sphincteroplasty is not recommended for the management of common bile duct

strictures caused by chronic pancreatitis because the stricture is too long to be managed adequately by

this technique. Similarly, endoscopic sphincterotomy has no role in the management of biliary

obstruction due to chronic pancreatitis. Limited experience has been reported with balloon dilation of

distal bile duct strictures secondary to pancreatitis, with little long-term follow-up.

Over the last decade another variant of chronic pancreatitis has been recognized as a cause of distal

bile duct stricture – autoimmune pancreatitis.43 This process is characterized by a lymphoplasmacytic

infiltrate and is associated with secretion of large amounts of immunoglobulin (Ig) 4. The condition can

mimic pancreatic cancer and is diagnosed by characteristic imaging studies and elevation of serum Ig4

levels. Treatment is with corticosteroids with surgical resection or bypass reserved for unresponsive

cases or when a diagnostic dilemma remains. Although Ig4 serology is highly sensitive (90%), cases

where equipoise remains can also undergo an initial empiric test of corticosteroids to assist in achieving

the diagnosis and potentially provide concurrent therapy.

MISCELLANEOUS CAUSES OF BILE DUCT STRICTURES

Benign strictures of the bile duct can result from the chronic inflammation associated with gallstones in

either the gallbladder or common bile duct. This cause of bile duct strictures is uncommon and is a rare

complication of gallstone disease. Bile duct strictures caused by cholelithiasis are usually associated with

a narrowing at the level of the common hepatic duct caused by a stone impacted in the infundibulum of

the gallbladder. The narrowing can be caused by two means. First, simple compression can occur from a

large stone lying adjacent to the common hepatic duct (Mirizzi type A). Second, chronic or acute

inflammation arising from the gallbladder or cystic duct can extend to the contiguous bile duct,

resulting in stricture formation (Mirizzi type B, C, or D). The biliary obstruction associated with either

of these conditions is known as Mirizzi syndrome and culminates in Mirizzi type E disease which occurs

in any case of bilioenteric fistula.44

The clinical presentation of a bile duct stricture caused by cholelithiasis is often associated with acute

cholecystitis and hyperbilirubinemia. In some long-standing cases, these findings exist in the face of

chronic gallbladder symptoms. If hyperbilirubinemia is present and urgent cholecystectomy is not

indicated, ERCP or PTC can help to delineate the preoperative biliary anatomy. Most cases that are

associated with acute cholecystitis, however, are recognized at the time of cholecystectomy and

operative cholangiography. When the duct compression is associated with acute inflammation, the

common hepatic duct almost always returns to normal after the offending stone has been removed by

cholecystectomy and the inflammatory process has resolved. Care must be taken during the dissection

1626

to avoid creation of a defect in the common hepatic duct. Rarely, after the acute episode has resolved, a

well-established stricture presents months to years after the acute episode. In such cases, management

by Roux-en-Y hepaticojejunostomy is appropriate.

Strictures due to choledocholithiasis are also rare. The presumed mechanism is erosion of the

epithelium of the distal duct, creating inflammation with subsequent fibrosis and stricture. Because of

the anatomic tapering of the common bile duct, nearly all stones are entrapped in the intrapancreatic

portion of the duct and are often difficult to remove by the supraduodenal route.

Excessive intraoperative manipulation at the time of bile duct exploration with forceps, scoops, and

catheters can often create additional trauma to an already friable distal duct. After the stone has been

removed, the distal bile duct should be gently sized with a soft rubber catheter to be sure that no

stricture exists. If a stricture persists after stone removal, it may not be recognized until the time of

postoperative T-tube cholangiography. If recognized in the postoperative period, time should be

allowed for resolution of inflammation before considering stricture repair. If a distal bile duct stricture

does persist, a biliary-enteric anastomosis with either Roux-en-Y choledochojejunostomy or a

choledochoduodenostomy is indicated. If the proximal duct is adequately dilated (>2 cm in diameter)

to allow a large choledochoduodenal anastomosis, this procedure is usually preferable because of its

technical ease and excellent results.

Stenosis of the sphincter of Oddi, or papillitis, is a benign intrinsic obstruction of the outlet of the

common bile duct, usually associated with inflammation, fibrosis, or muscular hypertrophy. Sphincter

stenosis can result in any of three clinical conditions: (a) common bile duct obstruction due to fibrotic

stenosis of the papilla, (b) recurrent pancreatitis, or (c) recurrent right upper quadrant pain without

jaundice or pancreatitis. The pathogenesis of the inflammation of sphincter stenosis is unclear. In many

cases, it is thought to result from the trauma of the passage of multiple small stones from the common

duct through the ampulla. This trauma results in inflammation, scarring, and stricture formation. Many

patients with papillary stenosis have no gallstones. Other potential mechanisms include primary

sphincter motility disorders and congenital anomalies. The clinical presentation is usually either

jaundice or cholangitis. In some cases, an impacted common bile duct stone may be present. The

diagnosis can be supported with either PTC or ERC. This condition can be managed by sphincterotomy

performed either endoscopically or operatively. If a cholecystectomy was performed previously,

endoscopic papillotomy is the initial procedure of choice.

Cholangiohepatitis is an unusual infection of the biliary tree frequently associated with Clonorchis

sinensis and other parasites. These infections are most commonly seen in natives of Asia. Most patients

present with recurrent episodes of cholangitis. Cholangiography can demonstrate multiple strictures of

both the intrahepatic and extrahepatic biliary tree, with the bile ducts filled with sludge and stones (Fig.

62-16). Surgical management consists of cholecystectomy and improved biliary drainage with either

Roux-en-Y choledochojejunostomy or choledochoduodenostomy. Access to the biliary tree for

postoperative management of intrahepatic stones or sludge should be maintained with either

transhepatic biliary stents or a choledochojejunocutaneous or subcutaneous fistula. No specific medical

management is available for this condition.

Finally, rare causes of benign intrahepatic and extrahepatic bile duct strictures have been reported

secondary to intrahepatic arterial infusion of 5-fluorouracil used in the treatment of hepatic metastases

of colorectal carcinoma. The clinical picture closely resembles primary sclerosing cholangitis but usually

can be managed by simple discontinuation of infusion and, in some cases, percutaneous transhepatic

drainage. Surgery should be reserved for patients with persistent evidence of biliary obstruction. A

similar cholangiographic appearance has been reported in patients with acquired immunodeficiency

syndrome. The pathogenesis of this injury is believed to be viral and related to cytomegalovirus

infection. No experience in the surgical management of this condition has been reported.

1627

 

level of obstruction were comparable in both groups. Surgical therapy consisted of Roux-en-Y

hepaticojejunostomy, and endoscopic therapy consisted of placement of an endoprosthesis with

trimonthly elective exchange for 1 year. Successful stent placement was accomplished in 94% of

patients managed endoscopically. Six of the 66 endoscopic patients, however, underwent surgical

reconstruction either for failed stent placement or for other reasons. Early complications occurred more

frequently in the surgically treated group (26% vs. 8%; p < 0.03). However, the only procedure-related

death occurred in a patient in whom severe pancreatitis developed after endoscopic stent placement.

Late complications, which included primarily episodes of cholangitis, occurred only in the endoscopic

group (27%). The overall complication rates, therefore, were similar at 26% for surgical patients and

35% for endoscopic patients. The mean follow-up and definition of success were similar to those in the

aforementioned study. After surgery, excellent results were observed in 83% of patients, with a

recurrent stricture developing in six patients at a mean of 40 months after the initial operation. After

endoscopic stenting, excellent results were observed in 72% of patients, with restricture developing in

18% of patients at a mean of 3 months after stent removal. The investigators concluded that endoscopic

stenting should be considered for the initial attempt at definitive management in suitable patients in the

hope of avoiding reoperation.

The final and most recent comparative study describing 528 patients over 18 years has confirmed a

number of interesting observations.23 More specifically, patients with all types of bile duct injuries were

most commonly treated by endoscopists (40%), followed by surgeons (36%) and interventional

radiologists (24%). Success rates however were higher for surgery (88%) compared to either endoscopy

(76%) or interventional radiology (50%). This observation was accomplished with an overall morbidity

amongst the surgical cohort of 24% with no 90-day mortality. Not surprisingly, outcomes also improved

dramatically over time amongst all approaches. Although the reason for this progress is clearly

multifactorial, issues such as improved selection of patients for each approach, increased experience in

reconstruction at the surgeon level (and therefore, fewer surgeons performing repairs overall), and

perhaps pursuit of more proximal biliary-enteric anastamoses and/or more selective use of transhepatic

stents may each play a role. Taken as a whole, this modern analysis of bile duct injuries confirms the

importance of ensuring significant clinician experience with this complication, a multidisciplinary team

comprised of HPB surgeons, interventional endoscopists and interventional radiologists, and thoughtful

selection of a given patient for the appropriate therapeutic option with the highest chance of long-term

success.

Table 62-5 Diseases Associated with Primary Sclerosing Cholangitis

PRIMARY SCLEROSING CHOLANGITIS

Primary sclerosing cholangitis is an idiopathic disease characterized by intrahepatic and extrahepatic

inflammatory strictures of the bile ducts that cannot be attributed to other specific causes. The cause of

primary sclerosing cholangitis is unknown. Many experts consider primary sclerosing cholangitis to be

an autoimmune reaction because it is associated with other autoimmune diseases, such as ulcerative

colitis, retroperitoneal fibrosis, and Riedel thyroiditis (Table 62-5). It is likely that a number of causes,

including viral or bacterial infections, toxic drug reactions, and congenital anomalies, can all result in

1622

the same end-stage injury that is recognized as primary sclerosing cholangitis.

The usual clinical presentation of patients with primary sclerosing cholangitis involves intermittent

jaundice, which begins insidiously in the fourth or fifth decade of life. Right upper quadrant pain,

pruritus, fever, weight loss, and fatigue can also occur. The disease is characterized by cyclic remissions

and exacerbations. Despite the nomenclature, acute cholangitis is uncommon without previous biliary

manipulation or surgery. The diagnosis is suggested by clinical presentation associated with cholestatic

liver function test abnormalities. The levels of bilirubin often fluctuate with respect to the remissions

and exacerbations of the disease and the extent of hepatic injury. Alkaline phosphatase is usually

elevated out of proportion to the serum bilirubin, and is a more persistent finding. The diagnosis,

however, usually is confirmed by cholangiography, which reveals multiple dilatations and strictures

(beading) of the intrahepatic and extrahepatic bile ducts (Fig. 62-13). MRCP has become the preferred

procedure as it is noninvasive. ERC, however, remains an important tool for both diagnostic and

therapeutic procedures. An important distinction must be made as cholangiocarcinoma must be

considered in the differential diagnosis of a dominant stricture. Furthermore, cholangiocarcinoma may

develop after presentation in up to 30% of patients with primary sclerosing cholangitis. Therefore,

endoscopic brushings and biopsies are frequently required. The disease should be followed closely by

cholangiography and liver biopsy to provide appropriate management before the development of biliary

cirrhosis.

Figure 62-13. A: Cholangiogram of a patient with primary sclerosing cholangitis. Multiple irregular strictures and dilatation

(beading) of intrahepatic bile ducts can be seen. B: Endoscopic retrograde cholangiogram showing extensive involvement of

extrahepatic bile duct (BD) with primary sclerosing cholangitis. (B reproduced with permission from Lillemoe KD, Pitt HA,

Cameron JL. Primary sclerosing cholangitis. Surg Clin North Am 1990;70:1390.)

No known specific medical therapy is effective for primary sclerosing cholangitis. The most

encouraging results, from a prospective, randomized, placebo-controlled trial, suggest that

ursodeoxycholic acid significantly improves serum liver function tests and liver histologic appearance.

Unfortunately, there were no significant differences in clinical outcome between the two groups at up to

6 years of follow-up.36 Nonoperative dilation therapy by the endoscopic route has been used for

dominant strictures with favorable results.37

8 An aggressive surgical approach is advocated for selected symptomatic patients with primary

sclerosing cholangitis because of the lack of effective medical therapy. One surgical approach, in

patients with a dominant stricture at the hepatic duct bifurcation, uses resection of the bifurcation and

long-term transhepatic stenting with Silastic stents. This mode of therapy was recently reported in 77

patients with resection of the hepatic duct bifurcation, with hepatic lobectomy performed in another

four patients.38 The perioperative complication rate was 39% and 30-day mortality was 3.9%. Bilirubin

1623

improved and 57% of patients had no primary sclerosing cholangitis–related readmissions. At median

follow-up of 10.5 years, the 5- and 10-year survival rates were 76.4% and 52.7%, respectively.

Cholangiocarcinoma did not develop in any patients and only seven required liver transplant. Over the

same period, liver transplant was performed in 49 patients with cirrhosis with a 10-year survival of

57%.

The role of biliary surgery in primary sclerosing cholangitis, however, has decreased considerably

with the growing success of liver transplantation. Primary sclerosing cholangitis has become one of the

most common indications for liver transplantation in the United States, with 5-year actuarial survival

and graft survival rates of 85% and 72%, respectively.39 Liver transplantation should be considered

before the disease is too advanced. The development of a poor quality of life as a result of disabling

fatigue, intractable pruritus, severe muscle wasting, and chronic or recurrent bacterial cholangitis or

persistent elevations in serum bilirubin are primary indications for referral for liver transplantation.

Preoperative recognition of cholangiocarcinoma is extremely important in this population in that the

development of this complication significantly worsens the result after liver transplantation. The

presence of known malignancy results in patients being refused transplantation. The microscopic

identification of intrahepatic cholangiocarcinoma in the absence of lymph node involvement, often

demonstrated in the explanted liver specimen, however, does not usually portend a poor prognosis.

Although it can be extremely difficult to confidently confirm or refute the presence of

cholangiocarcinoma in this setting, both MRCP and more recently SpyGlass cholangioscopy during

ERCP can be extremely helpful. SpyGlass cholangioscopy in particular provides the advantage of direct

visualization of the biliary mucosa/lesion, as well as an opportunity for biopsy.

Patients with primary sclerosing cholangitis have a significantly higher rate of development of

nonanastomotic biliary strictures after liver transplantation, with histologic features on

posttransplantation biopsy consistent with recurrence of the disease. Other causes of stricture, such as

hepatic artery thrombosis, preservation-related ischemia, cytomegalovirus infection, and chronic

ductopenic rejection, can cause similar lesions. Recurrent primary sclerosing cholangitis usually does not

have an aggressive course.

Resection of the hepatic duct bifurcation and long-term transanastomotic stenting in selected patients

can preclude or delay the need for hepatic transplantation. Moreover, this operation does not eliminate

or influence the results of hepatic transplantation. Resection of the hepatic bifurcation and long-term

transhepatic stenting can be recommended for selected patients with primary sclerosing cholangitis with

severe strictures at or distal to the hepatic duct bifurcation but without established biliary cirrhosis. In

patients with biliary cirrhosis, hepatic transplantation is recommended.

BILE DUCT STRICTURES SECONDARY TO CHRONIC PANCREATITIS

9 Chronic pancreatitis is an uncommon cause of benign bile duct strictures, resulting in less than 10% of

such cases. Transient partial obstruction of the distal common bile duct caused by inflammation and

edema frequently occurs in patients with acute pancreatitis. With chronic pancreatitis, however, the

clinical problem is distal bile duct obstruction caused by inflammation and parenchymal fibrosis of the

gland. These strictures classically involve the entire intrapancreatic segment of the common bile duct

and are associated with dilatation of the entire proximal biliary tree (Fig. 62-14). In most cases, the

cause of the chronic pancreatitis is alcoholism. Often, advanced disease is present in that the incidence

of pancreatic calcification, diabetes, and malabsorption is increased at the time of presentation with

jaundice compared with patients with chronic pancreatitis without jaundice. Common bile duct

strictures have been reported to occur in 3% to 29% of patients with chronic alcoholic pancreatitis. In a

review of a number of clinical series, the overall incidence of common bile duct strictures in patients

with chronic pancreatitis was 5.7%.40 The exact incidence of common bile duct strictures is not known,

however, because cholangiography is not routinely performed in patients with chronic pancreatitis.

The clinical presentation of patients with common bile duct strictures secondary to chronic

pancreatitis is variable. Some patients have no symptoms, with the diagnosis of bile duct strictures

suggested only by abnormal liver function test results. The serum alkaline phosphatase appears to be

the most sensitive laboratory finding and is elevated in more than 80% of patients. Abdominal pain with

or without jaundice is another common presentation. In some cases, the abdominal pain can be difficult

to distinguish from the pain associated with chronic pancreatitis. Failure to recognize and address a bile

duct stricture, however, can lead to ultimate failure of operative procedures performed for chronic pain

in patients with chronic pancreatitis. Finally, the development of jaundice in patients with chronic

1624

 

Figure 62-9. Technique of biliary reconstruction. A: A Silastic stent is sutured to the preoperatively placed transhepatic catheter,

which protrudes through the transected hepatic duct and through the catheter tract in the hepatic parenchyma. B: A Roux-en-Y

jejunal loop is then anastomosed to the hepatic duct and (C) the Silastic stent is placed through the anastomosis. D: A completed

Roux-en-Y hepaticojejunostomy with a transanastomotic stent.

Long-Term Results

6 Historically, excellent long-term results were achieved in 70% to 90% of patients who underwent

repair of bile duct strictures (Table 62-2). The definition of satisfactory results in most series requires

that patients have no symptoms, jaundice, or cholangitis. Length of follow-up is important in analyzing

final results because recurrent strictures can occur up to 20 years after the initial procedure (Fig. 62-

10).12,13 Approximately two-thirds of restrictures are evident within 2 years, and 90% are seen within 7

years. The percentage of patients with good results is inversely related to the number of previous

repairs. Other factors that favor a good outcome include young age at the time of stricture repair, use of

a Roux-en-Y biliary-enteric anastomosis, absence of infection and hepatic fibrosis, and use of

transhepatic stents.

RESULTS

Table 62-2 Results of Surgical Management of Bile Duct Strictures

1616

As illustrated earlier, in the era before laparoscopic cholecystectomy, excellent long-term results were

obtainable in tertiary care centers specializing in the management of these problems. Questions had

arisen as to whether the excellent results of bile duct strictures after open cholecystectomy could be

directly transferred to patients sustaining laparoscopic bile duct injuries. Some researchers had

suggested that the mechanism of bile duct injury during laparoscopic cholecystectomy, the complex

nature of many of these injuries, and the frequent association of significant inflammation and fibrosis

secondary to sustained, unrecognized bile leakage might result in poor long-term results. Furthermore,

the high percentage of these patients who have undergone unsuccessful operations, often performed by

the primary laparoscopic surgeon, might also lead to a poor long-term outcome. Evidence for the latter

hypothesis was provided by a review of the records of 85 patients who underwent a total of 112 biliary

repairs.24 Four factors determined the success or failure of treatment in this series. These factors

included performance of preoperative cholangiography, the choice of surgical repair, details of the

operative repair, and experience of the surgeon performing the repair. The importance of preoperative

delineation of anatomy was clear, in that 96% of procedures in which cholangiograms were not

obtained before repair were unsuccessful, and 69% of repairs were not successful when the

cholangiographic data were incomplete. When cholangiographic data were complete, the initial repair

was successful in 84% of patients. The type of repair was also of significance in influencing outcome. A

primary end-to-end ductal repair over a T-tube was unsuccessful in all patients in whom a complete

transection of the bile duct had taken place, whereas 63% of Roux-en-Y hepaticojejunostomies were

successful. Attempts at repair by the primary surgeon were successful only in 17% of cases, and in no

case was a secondary repair by the primary surgeon successful. In those cases in which the first repair

was performed by a tertiary care biliary surgeon, a 94% success rate was obtained.

The outcome of management of 142 patients with major bile duct injuries treated during the 1990s

has been reported.21 Laparoscopic cholecystectomy was the initial operation in 75% of these patients,

and 41% had undergone a previous attempt or attempts at surgical repair before referral. In this series

with a median follow-up of 58 months (range, 11 to 119 months), a successful outcome was obtained in

91% of patients. In this series the level of injury, clinical presentation, history of prior repair, and

length of biliary stenting did not influence outcome. Comparable results have been reported from other

high-volume hepatobiliary centers.22,25 These results suggest that surgical reconstruction of major bile

duct injuries after laparoscopic cholecystectomy can still result in excellent long-term results.

RESULTS

Table 62-3 Results of Transhepatic Balloon Dilation of Bile Duct Strictures

Despite the overall success of biliary reconstruction, there is a small subset of patients with major bile

duct injuries in whom standard repair techniques appear to be inadequate. Factors, such as delay in

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diagnosis, complex injuries above the hepatic confluence, associated vasculobiliary injuries, and liver

atrophy can all negatively affect the outcomes of standard reconstruction. In this select population

excellent results have been observed with major hepatectomy.26 A classic example of this scenario

would be a patient who has sustained a right posterior sectoral bile duct injury, and subsequent hepatic

atrophy with associated recurrent cholangitits. These patients typically benefit most from a right

posterior hepatic sectionectomy, as opposed to an attempt at a challenging hepaticojejunostomy

reconstruction to a small duct within an abnormal liver. Finally, in rare cases with failure of all standard

surgical techniques of reconstruction with resultant end-stage liver disease, liver transplantation may

offer the opportunity for survival.27 Interestingly, many of these extreme injuries are caused during

open cholecystectomy and therefore, trauma caused by migration from the cystic plate into the hilar

plate itself.11

Figure 62-10. The cumulative percentage of recurrent strictures with respect to the time from the initial repair until the next

repair. (Adapted from Pitt HA, Miyamoto T, Parapatis SK, et al. Factors influencing outcome in patients with postoperative biliary

strictures. Am J Surg 1982;144:14–21.)

Although large series from tertiary referral centers have reported excellent long-term results, the

overall impact of bile duct injuries on society is significant in terms of health care costs, disability, and

even mortality. In an analysis of patients undergoing laparoscopic cholecystectomy from the U.S.

Medicare database, Flum et al. demonstrated that the adjusted hazard ratio for death during the followup period was significantly higher (2.79, 95% confidence level 2.71–2.88) for patients with a bile duct

injury than in those patients without a bile duct injury.28 The hazard increased with advancing age and

comorbidities and decreased with the experience of the repairing surgeon. The adjusted hazard of death

during follow-up was 11% greater if the repairing surgeon was the same as the injuring surgeon. These

data certainly further support the referral of most patients with bile duct injuries to centers with greater

experience in the management of the injuries.

Finally, although the overall success of the surgical management of laparoscopic bile duct injuries

associated with laparoscopic cholecystectomy is excellent, there is an impression that patients may have

an impaired quality of life even after successful repair of their bile duct injury. Quality-of-life

assessments after laparoscopic cholecystectomy bile duct injury have been addressed in several recent

reports.29,30 These results have generally reported either comparable or mildly diminished quality of life

compared with matched controls. Interestingly, in one study, patients who reported pursuing a law suit

following their injury had significantly worse quality-of-life scores in all domains when compared to

those who did not entertain legal action.29 The most recent study, which spanned a 23-year period (169

month median follow-up), evaluated 62 patients who had generally undergone a Roux-en-Y

hepaticojejunostomy (86%) reconstruction, confirmed that mental health concerns were more common

place than physical or general health issues following bile duct injuries. While most patients displayed

an eventual return to their physical baseline, psychological quality of life was much more difficult to

correct over time.31

Nonoperative Management

Operative management of bile duct strictures is technically difficult and continues to be associated with

significant postoperative morbidity and mortality. Moreover, in all series, recurrent strictures develop

in a proportion of patients. These factors, in addition to technical advances in the fields of therapeutic

radiology and endoscopy, have led to the development of nonoperative techniques for management of

bile duct strictures. The optimal method for management using these techniques is dependent on the

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presence and anatomy of biliary-enteric continuity.

Percutaneous Balloon Dilation

The management of benign bile duct strictures using the percutaneous transhepatic route is indicated

primarily in patients with a failed prior biliary-enteric anastomosis to a jejunal limb. The procedure in

many cases can be performed with a combination of local anesthesia and intravenous sedation. In this

technique, access to the proximal biliary tree is gained and the stricture is traversed with a guide wire

under fluoroscopic guidance. At this point, the stricture is dilated using angioplasty-type balloon

catheters, chosen on the basis of the location of the stricture and the diameter of the normal duct (Fig.

62-11). After the procedure, a transhepatic stent is left in place across the stricture to allow access to the

biliary tree for follow-up cholangiography, repeat dilation, and maintenance of a lumen during the

healing process. In most series, numerous dilations are required.

The results from a number of series have been encouraging (Table 62-3). In a multicenter review of

bile duct strictures treated in the open cholecystectomy era, 3-year follow-up showed a 67% patency

rate for anastomotic and a 76% patency rate for iatrogenic primary bile duct strictures, yielding an

overall 70% success rate.32 A report of 51 patients with bile duct strictures after laparoscopic

cholecystectomy managed with percutaneous dilation showed a success rate of 58% with a mean followup of 76 months.33

Complications of balloon dilation are frequent. Cholangitis, hemobilia, and bile leaks can occur in up

to 20% of patients. Bleeding, usually from the hepatic parenchyma, has been reported, with transfusions

often necessary. Sepsis due to cholangitis can occur despite antibiotic prophylaxis. Sepsis and significant

bleeding seldom occur in patients dilated by a T-tube tract, suggesting that much of the morbidity is the

result of traversing the hepatic parenchyma by the large percutaneously placed catheters.

Endoscopic Balloon Dilation

Endoscopic balloon dilation is often considered technically possible only in patients with primary bile

duct strictures or with strictures at a prior primary end-to-end repair or choledochoduodenal

anastomosis. With the advent of double-balloon enteroscopy however, more patients are now able to

undergo endoscopic retrograde cholangiopancreatography (ERCP) following preceding

hepaticojejunostomies, as well as a myriad of bariatric procedures. In select cases, laparoscopic assisted

ERCP is also possible. This technique begins with ERC and endoscopic sphincterotomy. The stricture is

traversed retrograde with an atraumatic guide wire, and sequential balloon dilation is used.

Reevaluation with cholangiography is performed every 3 to 6 months. Redilation is performed as

necessary. In most cases, an endoprosthesis is left in place after dilation for at least 12 months.

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Figure 62-11. A: Transhepatic cholangiogram demonstrating stricture (arrow) at a previous choledochojejunostomy. B: Progressive

dilation of the strictured anastomosis with an angioplasty balloon catheter. C: Postdilation stenting of the anastomotic stricture for

prolonged periods. D: Subsequent cholangiogram demonstrating resolution of the anastomotic stricture. (Reproduced with

permission from Pitt HA, Kaufman SL, Coleman J, et al. Benign postoperative biliary strictures: operate or dilate? Ann Surg

1989;210:417–425; discussion 426–427.)

7 The reported experience with endoscopic dilation of benign bile duct strictures is shown in Table

62-4. The largest experience comes from the group in The Netherlands who recently reported their

experience in 110 patients.34 The mean number of stents placed was two, the mean duration of stenting

was 11 months, and stent-related complications occurred in 33% of patients with one death. Twenty

percent of patients were eventually referred for surgery. The overall reported success rate was 74%

with a mean follow-up of 7.6 years. A similar experience was reported in the United States.35 In this

series, 18 of 25 strictures were postoperative. Strictures were located at the cystic duct junction in 17

patients and in the distal bile duct in the remaining eight patients. Of 25 patients, 22 (88%) had

significant clinical benefit from the therapy. Only two complications occurred in this series – one case

each of pancreatitis and cholangitis.

Comparative Data

Comparison of results of nonoperative dilation with those of surgery has been difficult. Few centers

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have significant experience with both operative and nonoperative management. Furthermore, the

definition of a successful procedure, the reporting of complications, and the length of follow-up has not

been consistent in the literature. There are no prospective randomized studies to compare these

techniques; however, three retrospective comparative studies exist. In the first study, a retrospective

review of the results at the Johns Hopkins Hospital between 1979 and 1987 compared percutaneous

balloon dilation and surgery in 43 patients with benign postoperative bile duct strictures.19 Twenty-five

patients underwent surgical repair with Roux-en-Y hepaticojejunostomy with postoperative transhepatic

stenting for a mean of 13 ± 1.3 months. Twenty patients had percutaneous balloon dilation, a mean of

3.9 times, and were stented transhepatically for a mean of 13.3 ± 2 months. Three patients were

managed with both surgery and balloon dilation. The two groups were similar with respect to multiple

parameters that might have influenced outcome, including age, sex, associated medical problems, and

presentation with either obstructive jaundice or biliary fistulas. No patients died after any of the

procedures. Procedure-related morbidity occurred in 20% of surgical patients and in 35% of the patients

undergoing balloon dilation. For both groups, a successful outcome was defined as no evidence of

cholangitis or jaundice requiring another procedure more than 12 months from the onset of treatment.

A failed treatment was defined as the need for crossover to the other treatment modality, either

operation or dilation, or late death from liver failure, biliary sepsis, or portal hypertension. A successful

repair was achieved in 89% of the surgical patients and in only 52% of the balloon dilation patients

(Fig. 62-12). The overall late mortality rate in this series was 10%. One late death occurred in the

surgical group, whereas three late deaths followed balloon dilation (4% vs. 15%, respectively). No

deaths, however, were attributed to liver failure, biliary sepsis, or portal hypertension associated with

the bile duct stricture.

Table 62-4 Results of Endoscopic Balloon Dilatation of Bile Duct Strictures

To define further the relative benefits of the two procedures, total hospital stay and total procedural

costs were determined. As expected, initial hospitalization was longer for surgery than for balloon

dilation. When rehospitalization for further dilation, complications, or recurrences was considered, total

hospital stay did not differ significantly between the two groups. Cost data paralleled hospitalization

data and did not differ significantly between the groups. Thus, the authors concluded that until properly

designed, randomized, prospective, controlled trials can be performed, surgical repair for benign

postoperative strictures appears to be associated with fewer problems and a greater success rate.

Figure 62-12. Actuarial success rates over 72 months for surgery (89%) and balloon dilation (52%). The difference is statistically

significant (p < 0.01). (Adapted from Pitt HA, Kaufman SL, Coleman J, et al. Benign postoperative biliary strictures: operate or

dilate? Ann Surg 1989;210:417–425; discussion 426–427.)

In the second comparative study, the group from The Netherlands compared endoscopic versus

surgical treatment of benign bile duct strictures.21 Thirty-five patients were treated surgically, and 66

were treated by endoscopic stenting. Patient characteristics, initial injury, previous repairs, and the

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Figure 62-7. Endoscopic retrograde pancreaticocholangiogram showing filling of a normal pancreatic duct (PD). The common bile

duct (CBD), however, does not fill beyond the large clip that appears to be placed across the duct. (Reproduced with permission

from Lillemoe KD, Pitt HA, Cameron JL. Postoperative bile duct strictures. Surg Clin North Am 1990;70:1355–1380.)

The management of a suspected bile duct injury after laparoscopic cholecystectomy presenting with a

bile leak deserves special mention. Often, when bile leakage is suspected, the surgeon believes that

urgent surgical exploration is necessary. Unfortunately, at laparotomy, the marked inflammation

associated with bile spillage and the small decompressed biliary tree that appears retracted high into the

porta hepatis make recognition of the injury and repair virtually impossible. In such cases, every

attempt should be made to define the biliary anatomy by preoperative cholangiography (PTC or MRCP)

and to control the bile leak with percutaneous biliary drainage. In many cases, early operative

intervention is not required because the bile collections or ascites can either be drained percutaneously

or simply is absorbed from the peritoneal cavity. Delayed reconstruction, aided by percutaneous biliary

catheters, then allows optimal surgical results.14

In patients who present with a biliary stricture remote from the initial operation, symptoms of

cholangitis can necessitate urgent cholangiography and biliary decompression. Biliary drainage is best

accomplished by the transhepatic method, although successful endoscopic stent placement can also be

accomplished. Parenteral antibiotics and biliary drainage should be continued until sepsis is controlled.

In patients who present with jaundice but without cholangitis, cholangiography should be performed to

define the anatomy. Preoperative biliary decompression in patients without cholangitis has not been

demonstrated to improve outcome.

Surgical Management

The goal of operative management of bile duct stricture is the establishment of bile flow into the

proximal gastrointestinal tract in a manner that prevents cholangitis, sludge or stone formation,

restricture, and biliary cirrhosis. This goal is best accomplished with a tension-free anastomosis between

healthy tissues. A number of surgical alternatives exist for primary repair of bile duct strictures,

including end-to-end repair, Roux-en-Y hepaticojejunostomy or choledochojejunostomy,

choledochoduodenostomy, and mucosal grafting. The choice of repair depends on a number of factors,

including the extent and location of the strictures, the experience of the surgeon, and the timing of the

repair.

Immediate Repair of Intraoperative Bile Duct Injury

In many cases, initial proper management of bile duct injury recognized at the time of cholecystectomy

can avoid the development of a bile duct stricture. Unfortunately, recognition of a bile duct injury is

uncommon during either open or laparoscopic cholecystectomy. If bile leakage is observed or atypical

anatomy is encountered during laparoscopic cholecystectomy, early conversion to an open technique

and prompt cholangiography are imperative. If a segmental or accessory duct less than 3 mm has been

injured and cholangiography demonstrates segmental or subsegmental drainage of the injured ductal

system, simple ligation of the injured duct is adequate. If the injured duct is 4 mm or larger, however, it

is likely to drain multiple hepatic segments or the entire right or left lobe and thus requires operative

repair.

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If the injury involves the common hepatic duct or the common bile duct, repair should also be carried

out at the time of injury. The aims of any repair should be to maintain ductal length and not to sacrifice

tissue, as well as to affect a repair that will not result in postoperative bile leakage. To accomplish these

goals, all repairs at the time of initial operation should involve some sort of external drainage. If the

injured segment of the bile duct is short (<1 cm) and the two ends can be opposed without tension, an

end-to-end anastomosis can be performed with placement of a T-tube through a separate

choledochotomy either above or below the anastomosis (Fig. 62-8A). Generous mobilization of the

duodenum out of the retroperitoneum (Kocher maneuver) can be useful to help approximate the injured

ends of the bile duct. An end-to-end repair, however, should be avoided if the ductal injury is near the

hepatic duct bifurcation. It must also be remembered that in the nontransplantation setting, the patient

does not have the benefit of a lower stricture rate due to chronic immunosuppression.

Figure 62-8. All biliary anastomoses performed for the reconstruction of acute bile duct injury should have external drainage. A: If

the injured segment of bile duct is short (<1 cm) and the two ends can be opposed without tension, an end-to-end anastomosis

can be performed with placement of a T-tube through a separate choledochotomy either above or below the anastomosis. The Ttube should not be brought out directly through the anastomosis. B: With more proximal injuries or if the segment of injured bile

duct is greater than 1 cm, an end-to-end bile duct anastomosis should be avoided and a Roux-en-Y hepaticojejunostomy should be

constructed. A transanastomotic stent can be placed retrograde through the transected duct and exited to the hepatic parenchyma to

allow postoperative external drainage.

Figure 62-8. All biliary anastomoses performed for the reconstruction of acute bile duct injury should have external drainage. A: If

the injured segment of bile duct is short (<1 cm) and the two ends can be opposed without tension, an end-to-end anastomosis

can be performed with placement of a T-tube through a separate choledochotomy either above or below the anastomosis. The Ttube should not be brought out directly through the anastomosis. B: With more proximal injuries or if the segment of injured bile

duct is greater than 1 cm, an end-to-end bile duct anastomosis should be avoided and a Roux-en-Y hepaticojejunostomy should be

constructed. A transanastomotic stent can be placed retrograde through the transected duct and exited to the hepatic parenchyma to

allow postoperative external drainage.

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5 For proximal injuries or if the injured segment of the bile duct is greater than 1 cm in length, an

end-to-end bile duct anastomosis should be avoided because of the excessive tension that usually exists

in these situations. In these circumstances, the distal bile duct should be oversewn, and the proximal

bile duct should be debrided of injured tissue and anastomosed in an end-to-side fashion to a Roux-en-Y

jejunal limb. The use of a Roux-en-Y jejunal limb is preferable to anastomosis to the duodenum because,

in the latter case, an anastomotic leak results in a duodenal fistula. A transanastomotic Silastic stent can

be placed retrograde through the transected duct and exiting the hepatic parenchyma (Fig. 62-8B) to

allow for postoperative external drainage.

Unfortunately, most bile duct injuries during laparoscopic cholecystectomy occur in the hands of

surgeons who are not experienced in performing complex biliary reconstruction. In such settings, the

surgeon should consider not repairing the injury and not risk further worsening the situation. The biliary

tree should be drained via a retrograde catheter to facilitate cholangiography, but the bile duct should

not be ligated. More specifically, ligation of the proximal bile duct most often leads to stump necrosis,

subsequent bile leakage and a more challenging reconstruction due to proximal migration of the injury

itself.15 The subhepatic space should be well drained to control the biliary leak. Prompt transfer to a

tertiary hepatobiliary center should then be made.

The long-term results of immediate repair of common bile duct injuries are uncertain. Most injuries

occur away from major centers, and therefore, even the successes are unlikely to be reported in the

literature. In a Swedish report, early primary repair with end-to-end anastomosis resulted in good

outcomes in only 22% of patients. Anastomotic leak requiring reoperation occurred in 32% of patients,

and late stricture occurred in another 37% of patients. In patients undergoing immediate repair with a

biliary-enteric anastomosis, good results were seen in 54% of patients, with strictures occurring in only

12% of patients. Similar poor late results were observed in another series in which 29 of 36 patients

with primary end-to-end repair had postoperative strictures within 4 years.

Elective Repair of Bile Duct Injuries and Established Strictures

Several principles are associated with successful repair of a biliary injury or stricture: exposure of

healthy proximal bile ducts that provide drainage of the entire liver; preparation of a suitable segment

of intestine that can be brought to the area of the stricture without tension, most frequently a Roux-en-Y

jejunal limb; and creation of a direct biliary-enteric mucosal-to-mucosal anastomosis. A number of

alternatives for elective repair of bile duct strictures exist. The choice of procedure is dictated by the

location of the stricture, the history of previous unsuccessful attempts at repair, and the surgeon’s

personal preference. Simple excision of a bile duct stricture and end-to-end bile duct anastomosis or

repair of the damaged duct can rarely be accomplished because of the invariable loss of duct length as a

result of fibrosis associated with the injury. Similarly, anastomosis of the proximal bile duct to the

duodenum as a choledochoduodenostomy is not suitable for most postcholecystectomy strictures

because an adequate length of bile duct for creating a tension-free anastomosis to the duodenum usually

cannot be obtained. Thus, in almost all cases, hepaticojejunostomy constructed to a Roux-en-Y limb of

jejunum is the preferred procedure.

Many surgeons believe that a transanastomotic stent is helpful in almost all cases. In the early

postoperative period, a stent is used to decompress the biliary tree and provide access for

cholangiography. If the injury involves the common bile duct or the common hepatic duct at least 2 cm

distal to the hepatic duct bifurcation, and adequate proximal bile duct mucosa can be defined, the use of

long-term biliary stents is not necessary. In these situations, the preoperatively placed percutaneous

transhepatic catheter or operatively placed T-tube is used to decompress the biliary-enteric anastomosis

for 4 to 6 weeks after surgery. When adequate proximal bile duct is not available for a good mucosa-tomucosa anastomosis, long-term stenting of the biliary-enteric anastomosis with a Silastic transhepatic

stent is recommended. For strictures involving the hepatic duct bifurcation, both the right and left main

hepatic ducts should be individually stented.

An operative technique for biliary reconstruction with transhepatic stents using the preoperatively

placed percutaneous transhepatic catheters begins with dissection of the porta hepatis, which usually

involves separating adhesions of the duodenum and hepatic flexure of the colon to the Glisson capsule

and gallbladder fossa.16 Identification of the proximal biliary segment can be difficult and can be aided

by the presence of the transhepatic biliary catheter. This is particularly true for bile duct transections

that will retract high into the porta. If a primary duct stricture exists, the bile duct is then divided at the

lowest extent of the stricture and dissected proximally. A segment of the strictured duct should be

resected and submitted for pathologic examination. The distal duct is then oversewn, and the bile duct

1614

proximal to the stricture is carefully dissected circumferentially in a cephalad direction for a distance

not to exceed 5 mm. Excessive dissection should be avoided to prevent vascular compromise of this

segment of duct, which will be used for the anastomosis. After mobilization and division of the bile

duct, the biliary catheters protrude through the proximal end (Fig. 62-9A). A radiologic guide wire is

then placed through these catheters. The preoperatively placed catheter can then be exchanged over the

wire for a properly sized Silastic stent. These stents are 70 cm long and range from 12 French to 22

French. Multiple side holes are present along 40% of the length of the stent. These side holes are left to

reside within the intrahepatic biliary tree and the portion of the Roux-en-Y jejunal limb used for the

biliary anastomosis. The end of the stent without the side holes exits through the hepatic parenchyma

and is brought out through a stab wound in the upper anterior abdomen. After stent placement, a Rouxen-Y jejunal limb is prepared, and the anastomosis is then performed as an end-to-side

hepaticojejunostomy (Fig. 62-9B–D).

The importance of the hilar (epicholedochal) arterial plexus in cases of proximal bile duct injuries is

also worth mention. More specifically, performing a “high” hepaticojejunostomy reconstruction to an

intact proximal hilar bridge between the right and left hepatic ducts utilizes robust crossing arterial

anatomy and is believed by many surgeons to minimize the risk of subsequent biliary stenosis.

An alternative technique has been described for management of bile duct strictures involving the

bifurcation and one or both of the hepatic ducts in which a side-to-side anastomosis of the left hepatic

duct to the Roux-en-Y limb is constructed. A long opening along the anterior surface of the left hepatic

duct is anastomosed to the side of the Roux-en-Y limb. Because it is possible to dissect the anterior

surface of the left hepatic duct high up into the hepatic parenchyma, this procedure permits anastomosis

to normal mucosa, even though there can be fibrosis and stricture at the bifurcation of the ducts and in

the distal portion of the hepatic duct. This technique can avoid the need for postoperative stenting.

Surgical Outcome

Morbidity and Mortality

Repairs of bile duct strictures are performed primarily in major medical centers by experienced

surgeons, yet these operations are still associated with significant morbidity and mortality. In 1982, a

review of 38 series published since 1900 that included more than 7,643 procedures performed on 5,586

patients reported an overall operative mortality rate of 8.3%.17 More recently the incidence of

operative mortality has decreased markedly with improved technology and a multidisciplinary

approach, as well as improved surgical experience. A recent series of 200 consecutive patients managed

at the Johns Hopkins Hospital reported three deaths in patients who did not undergo an attempt at

repair who were referred with sepsis secondary to an uncontrolled biliary leak, for a mortality rate of

1.5%. Definitive surgical reconstruction was performed in 175 patients with a perioperative mortality of

only 1.7%.18 In this series the timing of repair, the mode of presentation, previous attempts of repair,

and the level of injury did not influence outcome. Chronic liver disease can be an important factor for

operative mortality and morbidity with advanced biliary cirrhosis and portal hypertension leading to

mortality rates approaching 30%. Fortunately in the modern era, such advanced disease is uncommon.

In most series postoperative morbidity rates are in the range of 20% to 40%. In the recent Hopkins

series, complications occurred in 41% of patients. Most of the complications were minor and could be

managed with either interventional radiology techniques or conservative management. No patient

required reoperation for postoperative complications. The median length of stay in this series was 8

days.

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