Bile Duct Tumors 

Updated: Apr 27, 2022
Author: Todd A Nickloes, DO, FACOS; Chief Editor: John Geibel, MD, MSc, DSc, AGAF 


Practice Essentials

Tumors of the biliary tract are uncommon but potentially serious problems, with a spectrum of of severity that ranges from benign tumors such as adenomas to malignant lesions such as adenocarcinomas. This discussion excludes tumors of the gallbladder, which are discussed separately.

Tumors of the bile duct constitute about 2% of all cancers found at autopsy. Benign adenomas or papillomas are exceedingly rare in comparison  with malignant tumors. Even benign tumors tend to recur after excision and have been reported to undergo malignant change. Patients usually present with jaundice. Occult gastrointestinal (GI) hemorrhage may occur.

Cholangiocarcinomas, the most important primary tumors of the bile ducts, may involve either the intrahepatic or the extrahepatic biliary ducts.[1] The former variety is the second most common primary hepatic malignancy, after hepatocellular carcinoma. Patients with intrahepatic cholangiocarcinoma (cholangiocellular carcinoma) have a poor prognosis, and the tumor metastasizes early. This tumor has been associated with thorium dioxide (Thorotrast, an intravenous contrast medium used many years ago), ulcerative colitis, and sclerosing cholangitis; surgery is the only chance of treatment.

Bile duct cancer differs from gallbladder cancer in that it is distributed more evenly between males and females, and the course is more prolonged. All cholangiocarcinomas are slow-growing and locally infiltrative, and they metastasize late.

Most patients with bile duct tumors present with jaundice due to obstruction of the biliary tree by the tumor. Because the tumors are generally small, standard imaging studies, such as ultrasonography (US)[2]  and computed tomography (CT), may fail to show the lesion. These techniques may, however, provide a clue to the level of the obstruction and help exclude metastatic disease.

Cholangiography via a transhepatic or endoscopic approach is required to define the biliary anatomy and the extent of the lesion. Magnetic resonance cholangiography is a noninvasive alternative available in an increasing number of centers.

The anticipated course of most cases of bile duct tumors includes recurrent biliary obstruction with infectious complications, local spread, and death in 6-12 months. Treatment depends on the site and extent of the lesion, and surgical resection improves survival and prognosis.


The liver is an epithelial-mesenchymal outgrowth of the caudal part of the foregut, with which it retains its continuity by the biliary tree. Hepatocytes in the liver are arranged in anatomic plates called hepatic laminae, which are lined by endothelium and separated from each other by hepatic sinusoids. Bile secreted by hepatocytes is collected in a network of canaliculi, which drain into hepatic ductules. In turn, the hepatic ductules join other ductules, forming the biliary tree.

The main right and left hepatic ducts from the liver unite near the right end of the porta hepatis to form the common hepatic duct (CHD), which descends for about 2.5 cm before being joined by the cystic duct to form the common bile duct (CBD). The CHD lies to the right of the hepatic artery and anterior to the portal vein.

The CBD is 7.5 cm long and consists of three parts. The upper third lies in the free border of the lesser omentum anterior to the portal vein and to the right of the hepatic artery. The middle third lies behind the first part of the duodenum and slopes down to the right, eventually lying on the inferior vena cava. The lower third slopes down to the right behind the head of the pancreas, lying in a deep groove on the posterior surface of this organ. It opens, in common with the pancreatic duct, into the ampulla of Vater, which is situated in the second part of the duodenum.

The hepatic ducts and the upper and middle portions of the CBD are supplied with blood primarily by rami from the cystic artery. In addition, the middle portion of the CBD is supplied by rami from the right hepatic and posterior superior pancreaticoduodenal arteries. The latter also supplies blood to the lower portion of the CBD. Veins from the upper portion of the biliary tree enter the liver, and those from the lower portion drain into the portal vein.

With regard to lymphatic drainage, the upper portion of the biliary tree drains into the hepatic nodes, whereas the lower portion drains into the inferior hepatic and upper pancreaticosplenic nodes. Metastases from bile duct tumors can occur in lymph nodes lying along the common hepatic artery and the celiac axis and from distal lesions in the retropancreatic and superior mesenteric nodes.

Anatomically, the upper third of the biliary tree extends from the confluence of the hepatic ducts to the level of the cystic duct, the middle third extends from the cystic duct to the upper part of the duodenum, and the lower third extends from that level to the papilla of Vater.

The reported distribution of bile duct tumors is 55% in the upper third, 15% in the middle third, and 10% in the lower third. Of these tumors, 10% are diffuse.

Tumors of the bifurcation of the hepatic ducts are classified by the Bismuth classification, as follows:

  • Type I - Involvement of the CHD
  • Type II - Involvement of the bifurcation without involvement of the secondary intrahepatic ducts
  • Type IIIa - Extends into the right secondary intrahepatic duct
  • Type IIIb - Extends into the left secondary intrahepatic duct
  • Type IV - Involvement of the secondary intrahepatic ducts on both sides


Bile duct tumors cause bile duct obstruction with biliary stasis and a consequent alteration of liver function test results. Prolonged biliary obstruction causes hepatocellular dysfunction,[3] progressive malnutrition, coagulopathy, pruritus, renal dysfunction, and cholangitis.

Longstanding inflammation with the development of chronic injury is the final common pathway for tumorigenesis in the bile ducts in patients with preexisting inflammatory conditions.

Parasitic organisms induce DNA changes and mutations through the production of carcinogens and free radicals and the stimulation of cellular proliferation of the biliary epithelium, which is thought to cause cancer.

Bacterially induced endogenous carcinogen-derived bile salts, such as lithocholate, also have been implicated in the pathogenesis. These implications are supported by the findings of some epidemiologic studies and in the higher incidence in typhoid carriers.

Point mutations in codon 12 of the K-ras oncogene are found in cholangiocarcinoma.[4] Aneuploidy is found in hilar cholangiocarcinoma and is associated with neural invasion and shorter survival. P53 protein is particularly expressed in high-grade midduct and distal duct cholangiocarcinomas.[5] Cholangiocarcinoma cells contain somatostatin-receptor RNA, and cell lines have specific receptors. Cell growth is inhibited by somatostatin analogues. Cholangiocarcinomas have been detected using by radionuclide scanning with a labeled somatostatin analogue. Unique preinvasive lesions appear to precede different types of cholangiocarcinoma (ie, intrahepatic, perihilar, and distal).[6]


Risk factors for bile duct cancer include the following[7, 8] :

Patients with bile duct cancer may have a family history of congenital hepatic fibrosis, cystic dilatation (ie, Caroli disease), choledochal cyst, polycystic liver, or von Meyenburg complexes.

In the Far East (ie, China, Hong Kong, Korea, Japan), where Clonorchis sinensis (a liver fluke) is prevalent, intrahepatic cholangiocarcinoma accounts for 20% of primary liver tumors.[9]  Opisthorchis viverrini is found in Thailand, Laos, and West Malaysia.

The risk of extrahepatic bile duct cancer is significantly decreased 10 years or more after cholecystectomy, thus suggesting a link between bile duct cancer and gallstones. The risk is much less than that of carcinoma of the gallbladder, which is itself quite rare.

Among patients undergoing liver transplantation for PSC, 10-30% are found to have unsuspected cholangiocarcinoma in the hepatectomy specimen. Carcinoembryonic antigen (CEA) and carbohydrate (cancer) antigen (CA) 19-9 have, in combination, a sensitivity of 66% and a specificity of 100% in diagnosing cholangiocarcinoma in patients with PSC.

The majority of patients with PSC who develop cholangiocarcinoma have ulcerative colitis. The incidence of cholangiocarcinoma in patients with ulcerative colitis and PSC is further increased if they have an associated colorectal malignancy. Patients with PSC who develop a rapid deterioration in clinical status with worsening jaundice, weight loss, and abdominal discomfort and who have evidence of intrahepatic biliary dilatation on US[2] of the abdomen are suspected of having cholangiocarcinoma.

Toxic materials associated with an increased risk of bile duct cancer include thorium dioxide, radionuclides, and carcinogens (eg, arsenic, dioxin, nitrosamines, and polychlorinated biphenyls).

Drugs associated with an increased risk of bile duct cancer include oral contraceptives, methyldopa, and isoniazid.

Chronic typhoid carriers appear to have a greater incidence of hepatobiliary cancer, including cholangiocarcinoma.

Bile duct cancers are also associated with biliary cirrhosis.

Metabolic conditions (eg, diabetes and nonalcoholic fatty liver disease) also appear to be risk factors for intrahepatic and extrahepatic cholangiocarcinoma.[10]


The annual incidence of bile duct cancer in the United States is approximately 1 case per 100,000 people. In autopsy studies, the incidence has ranged from 0.01% to 0.46%. Patients with bile duct tumors are typically elderly; the average age is 60-65 years. In contrast to carcinoma of the gallbladder, only a minor sex difference in incidence exists, with a very slight male preponderance.

Bile duct cancer is more common in Israel and Japan and in American Indians than it is in the general US population. The prevalence of carcinoma of the gallbladder and bile ducts in England and Wales is 2.8 cases per 100,000 females and 2 cases per 100,000 males.


In patients with bile duct tumors, the choice of treatment and the prognosis are influenced greatly by the location of the tumor. The prognosis is better for distal bile duct tumors, histologically differentiated tumors, and polypoidal tumors. Factors that suggest poor prognosis include involvement of lymph nodes, vascular invasion, advanced T stage, positive tumor margins of the resected specimen, and the presence of mutations of P53.[5]

With hilar cholangiocarcinoma, the overall resection rate in most series is in the range of 40-60%. The mean survival rate for patients undergoing curative resection is 67-80% at 1 year and 11-21% at 5 years. Local resection has a lower operative mortality (8%) than does major hepatic resection (15%), with a mean survival of 21 months vs 24 months for major hepatic resection. There is no clear indication of better survival with major hepatic resection than with local bile duct resection, though some studies suggest that hepatic resection is associated with a greater incidence of tumor-free margins and, consequently, survival.

In distal bile duct cancers, the resection rate is higher than 60%, and the prognosis is better than for hilar tumors, the mean survival being 39 months. The survival rate is 50-70% at 1 year and 17-39% at 3 years.

In a study of 188 consecutive patients who underwent resection of intrahepatic cholangiocarcinoma, Doussot et al reported estimated survival rates of 59% at 3 years and 45% at 5 years.[11] The investigators found both the Wang nomogram and the Hyder nomogram to provide accurate estimates of prognosis after liver resection for intrahepatic cholangiocarcinoma. Diffuse intrahepatic tumors have a dismal prognosis; most patients with these tumors die within 1 year of diagnosis.

If left untreated, 50% of patients with bile duct cancer may survive for 1 year, 20% may survive for 2 years, and 10% may survive for 3 years.




Jaundice is the usual presenting symptom, followed by pruritus, which is a feature distinguishing a bile duct tumor from biliary cirrhosis. Jaundice is delayed if only one main hepatic duct is involved, because the unaffected lobe of the liver can compensate.

One third of patients present with mild epigastric pain. Diarrhea, anorexia, and weight loss are the other presenting symptoms.

Physical Examination

On examination, patients usually are deeply jaundiced. Cholangitis usually occurs only if previous endoscopic, percutaneous, or surgical biliary interventions have been performed. The liver may be large and smooth.

In distal bile duct tumors, a distended, nontender gallbladder may be present. If such patients undergo surgery and exploration confirms absence of involvement of the junction of the cystic duct and the common bile duct (CBD) by tumor, the gallbladder may be used for bypass procedures.

Cases with involvement of only one duct at the hilum present with mild abdominal pain, unilobar hepatic enlargement, and elevated serum alkaline phosphatase and gamma glutamyl transferase without any elevation of serum bilirubin.



Laboratory Studies

Results of liver function tests (LFTs) are suggestive of cholestasis in patients with bile duct tumors. Fluctuations in serum levels reflect incomplete obstruction or primary involvement of only one hepatic duct. In complete obstruction, serum bilirubin is markedly elevated. Serum alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) also are markedly elevated because they are markers of bile duct injury. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT), which mark hepatocellular damage, usually are only mildly elevated.

Patients usually are anemic. The leukocyte count may be high normal, with a preponderance of polymorphs. Levels of serum carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP) usually are normal and not elevated. A serum mitochondrial antibody test also produces negative results.

Feces are pale and fatty, with occasional blood.

Imaging Studies


Ultrasonography (US) of the liver is the investigation of first choice in patients with obstructive jaundice; US scans usually reveal dilated intrahepatic biliary ducts.[2] The extrahepatic duct may be collapsed if the tumor is high (eg, a Klatskin tumor at the bifurcation). A tumor mass may be observed in 40% of cases as a hyperechoic lesion. The absence of dilatation of intrahepatic bile ducts suggests an alternate diagnosis, such as drug-related jaundice or primary biliary cirrhosis.

Computed tomography

Computed tomography (CT) of the abdomen demonstrates intrahepatic biliary dilatation and lobar atrophy, but tumor mass may be difficult to demonstrate.[12] Calcification may be observed. CT is useful in diagnosing the level of obstruction in nearly all patients, and a specific diagnosis is possible in 78% of patients. Spiral (helical) CT allows accurate analysis of the relation between vascular and bile duct anatomy at the hilum. Multidetector CT (MDCT) has been been found to have value for assessing longitudinal tumor extent, vascular invasion, and resectability in extrahepatic bile duct cancer.[13]  

Magnetic resonance imaging

Magnetic resonance imaging (MRI) of the abdomen may be performed, but it adds little to US and CT with respect to establishing the diagnosis of extrahepatic cholangiocarcinoma.[14]  MRI cholangiography may be valuable and is increasingly available in specialized centers.[15, 16, 17]  MRI may be helpful for assessing depth of invasion in distal bile duct cancer, thereby facilitating staging.[18]

Angiography and cholangiography

Digital subtraction angiography (DSA) is useful in the preoperative assessment of resectability and demonstrates the anatomy of the hepatic artery and portal vein.

Cholangiography is indicated in any patient who is cholestatic with nondilated bile ducts when the diagnosis is in doubt. The choice of cholangiographic investigation depends on the site of the tumor.

In proximal lesions, percutaneous transhepatic cholangiography (PTC) defines the extent of the tumor and allows the preoperative placement of percutaneous catheters.[19]

Endoscopic retrograde cholangiopancreatography (ERCP) is of greater value in the diagnosis of distal tumors and permits the placement of endoprostheses (see the image below).[20]

Endoscopic retrograde cholangiopancreatography (ER Endoscopic retrograde cholangiopancreatography (ERCP) shows a narrowed area in the distal common bile duct with dilatation of the proximal biliary tree.

Presenting patterns of cholangiocarcinoma

Radiologically, cholangiocarcinomas present in three distinct patterns, as follows.

An intrahepatic mass is observed in 20-30% of cases. Calcification may be present. US reveals a hypoechoic, hyperechoic, or mixed echogenicity mass, whereas CT reveals a low-density, heterogeneous, and often peripherally enhancing mass.

A hilar Klatskin tumor is the most common pattern. US and CT of the abdomen show intrahepatic biliary dilatation with a normal-appearing cystic duct and hilar mass. In addition, segmental or lobar atrophy may exist. Portal and retroperitoneal adenopathy also are common. Cholangiography is diagnostic, with a stricture observed straddling the bifurcation and isolated right and left systems.

The distal duct form presents as a stricture and (less commonly) as a polypoid-filling defect. The stricture may be irregular, with overhanging edges suggestive of a malignant stricture, or it may be smooth and indistinguishable from benign strictures.


Tissue diagnosis can be obtained by means of percutaneous fine-needle aspiration (FNA) biopsy, brush-and-scrape biopsy, or cytologic examination of bile.[21, 22] However, these techniques provide a definitive diagnosis in only 30-50% of patients. If surgery is contemplated, preoperative tissue diagnosis is not essential, and surgical exploration is indicated.

Histologic Findings

A bile duct tumor is typically quite small (see the image below); 95% are adenocarcinomas of varying differentiation. Grossly, the tumor may be nodular or papillary or may present as a stricture (scirrhous variety).

Distal common bile duct tumor excised by radical p Distal common bile duct tumor excised by radical pancreaticoduodenectomy. The tumor measured 1.2 cm in diameter.

Nodular bile duct tumors form extraductal nodules in addition to intraluminal projections. The papillary variety most commonly is found in the distal bile duct and may fill the duct lumen with friable, vascular neoplastic tissue, which may cause hemobilia. The scirrhous variety usually is confined to the hilar area and forms gray, anular thickenings with clear defined edges. Distinguishing this variant from sclerosing cholangitis occasionally is difficult, even on histologic grounds.

Microscopically, the tumor usually is a mucin-secreting adenocarcinoma with a cuboidal or columnar epithelium, and spread along neural sheaths may be noted.[21] The scirrhous variety is intensely fibrotic and relatively acellular, often with a few well-differentiated ductal cancer cells grouped as acini in a dense connective-tissue stroma. Rare types include squamous cell carcinoma, adenosquamous carcinoma, adenoacanthoma, mucoepidermoid carcinoma, cystadenocarcinoma, granular cell carcinoma, lymphoma, carcinoid tumors, and melanoma. Malignant smooth-muscle tumors of the bile duct and nonsecreting apudomas of the hilar region also have been reported.

Immunohistochemistry and molecular biologic studies show that in addition to CEA, many tumors also stain positively for carbohydrate (cancer) antigen (CA) 50 and CA 19-9. Some reports also have identified mutations in K-ras oncogenes in 60-70% of intrahepatic and perihilar bile duct cancers. Further studies have identified abnormalities on chromosomes 5 and 17 and have documented the presence of c-erb oncogenes, epidermal growth factors, and proliferating nuclear antigens.[4, 23]

The diagnosis of bile duct cancers may be supported by positive findings in two of the following three indicators:

  • Positive reaction to CEA
  • Nuclear size variation
  • Formation of distended intracytoplasmic lumina

Neural invasion is another histologic finding that confirms a diagnosis of bile duct cancer.


Bile duct tumors are staged according to the tumor-node-metastasis (TNM) system of classification developed by the American Joint Comittee on Cancer (AJCC). Three different classification schemas are used, depending on the location of the tumor, as follows[24] :

  • Intrahepatic bile duct tumors
  • Perihilar bile duct tumors
  • Distal bile duct tumors

For more information, see Biliary Tract Cancer Staging.



Approach Considerations

Indications for bile duct tumor surgery include the following:

  • The tumor is resectable - Criteria for resectability include absence of liver metastases, absence of carcinomatosis, and absence of vascular invasion
  • The patient is fit for surgery

If the tumor is limited to the bifurcation of the hepatic ducts or a single lobe of the liver or if it involves the portal vein or hepatic artery on the same side, the lesion may be resectable. Preoperative imaging is aimed at establishing whether a viable unit of liver that is large enough to maintain adequate liver function will remain after surgical removal of the tumor. The remaining liver tissue must contain a normal branch of the portal vein and hepatic artery and must also contain a bile duct large enough to anastomose to the bowel (see the image below).

Operative photograph of choledochojejunostomy, sho Operative photograph of choledochojejunostomy, showing ample size of common duct.

Contraindications for surgery include the following:

  • Unresectable tumors - If tumors are extensive or fixed to adjoining structures, including the main portal vein or hepatic artery, they are unresectable; cholangiographic evidence of invasion of the secondary hepatic duct in both lobes of the liver or angiographic evidence of encasement of the main portal vein or hepatic artery indicates unresectability.
  • Metastases including diffuse peritoneal involvement
  • Vascular invasion
  • Patients who are at high risk from general anesthesia and surgery because of general medical conditions
  • Advanced age

The role of adjuvant radiotherapy and chemotherapy has been controversial.[25, 26, 27]  A meta-analysis by Ma et al found that adjuvant chemotherapy was associated with improved overall survival and should be considered in patients with intrahepatic cholangiocarcinoma following curative resection.[28]

The use of hormones in treatment, including somatostatin analogues, cholecystokinin, and cholecystokinin antagonists, is being investigated.

It has been suggested that preoperative endoscopic retrograde cholangiopancreatography (ERCP) with biliary drainage in patients with tumors of the bile duct increases the risk of implantation metastases after resection of the tumor.[29] Therefore, preoperative radiotherapy is advocated in such patients, but the benefit has not been definitely proved.[30]

Transarterial chemoembolization (TACE), infusion of 5-fluorouracil (5-FU) into the hepatic artery or bile ducts, and percutaneous injection of ethanol (PEI) into the lesions are other modalities that are investigational.

Photodynamic therapy may be useful in relieving obstruction, especially when obstruction occurs as a result of tumor outgrowth into an endoprosthesis.[31, 32]  Radiofrequency ablation (RFA) and intraluminal brachytherapy are being studied as well.[33, 34]

Liver transplantation, when performed for cholangiocarcinoma, is associated with poor survival.[35]

For more information on treatment of malignant bile duct tumors (cholangiocarcinomas), see Cholangiocarcinoma.

Nonoperative Therapy

Medical therapy is indicated for patients who are unfit for surgery or who have an unresectable tumor. Jaundice and itching can be reduced with the placement of an endoprosthesis, either endoscopically or percutaneously, across strictures.

Endoscopic techniques for the relief of obstruction include sphincterotomy, balloon dilatation of the stricture, and the placement of stents.[36, 20] Larger, expandable metal stents, which have better patency rates than do plastic stents, include Metal-Palmaz, Strecker, Gianturco Z stent, and Wall stents.[37] One meta-analysis suggested that covered self-expandable metal stents have a trend toward later obstruction as compared with uncovered self-expandable metal stents.[38]

Percutaneous transhepatic endoprosthetic insertion also is successful, but an increased risk of complications, such as blood and bile leakage, exists. Ninety percent of stents can be placed by a combination of endoscopic and percutaneous techniques after a failed endoscopic attempt.

Chemotherapy has been tried in these patients but has not been proved to be of definite benefit.[25] A phase II clinical trial by Schinzari et al suggested that the FOLFOX-4 regimen (5-fluorouracil/leucovorin plus oxaliplatin) is a potentially promising first-line treatment.[39] A regimen of gemcitabine plus cisplatin has been used for advanced cholangiocarcinoma.[40]

In April 2020, the US Food and Drug Administration (FDA) approved pemigatinib (Pemazyre) for previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor (FGF) receptor (FGFR) 2 gene (FGFR2) fusion or other rearrangement as detected by an FDA-approved test. Pemigatinib is a small-molecule kinase inhibitor that targets FGFR1, 2, and 3 by inhibiting FGFR1-3 phosphorylation and signaling. FGFR inhibition disrupts tumor cell proliferation, survival, migration, and angiogenesis. 

Approval of pemigatinib was supported by the FIGHT-202 study (n = 146).[41] Of the 146 patients enrolled, 107 had FGFR2 fusions or rearrangements, 20 had other FGF/FGFR alterations, 18 had no alterations, and 1 had an undetermined alteration. Thirty-eight (35.5%) of the 107 patients with FGFR2 fusions or rearrangements achieved an objective response (3 complete responses; 35 partial responses).

Radiotherapy may be administered by external beam therapy; intraoperative radiotherapy using biliary stents with iridium (192Ir), radium, or cobalt (60Co); radioimmunotherapy using sodium iodide (131I) anti-carcinoembryonic antigen (CEA) as a component of therapy; or charged particle irradiation. Internal radiotherapy may be combined with biliary drainage, but the value of this approach remains to be proved.[26, 27]

Pain may be relieved with the injection of 50% alcohol for chemical splanchnicectomy.

Immunotherapy has shown limited efficacy in cholangiocarcinoma (~5%).[42]  Some evidence suggests that immunotherapy targeting programmed cell death protein-1 (PD-1) may prove safe and effective for advanced intrahepatic cholangiocarcinoma.[43]

Surgical Therapy

Resection is the best treatment for bile duct tumors and provides the best palliation in terms of duration and freedom from infectious complications.[44, 45] Benefits of resection include the possibility of cure or long-term survival, especially for patients with distal tumors. The type of surgical procedure performed depends on the site and extent of the disease.

Choice of surgical approach

Proximal tumors (Klatskin tumors) may be managed by a variety of techniques, including the following:

  • Patients with perihilar tumors (Bismuth classification I and II), without evidence of vascular invasion, are candidates for local excision; if  negative margins cannot be achieved with local excision, resection of the corresponding lobe is indicated
  • Type III tumors are best managed by means of right or left hepatic lobectomy; resection of the adjacent caudate lobe (segment I) may ensure adequate tumor-free margins in cases of involvement of the hepatic duct bifurcation
  • Sometimes, extended right or left hepatectomy and (rarely) central liver resection may need to be combined for adequate resection of the tumor

Following resection of the bile duct, which may be combined with hepatic resection, reconstruction can be performed by means of unilateral or bilateral hepaticojejunostomy, using transhepatic stents.[37]

Surgical exploration is indicated in patients who are fit for surgery when preoperative evidence of metastases is absent or when locally unresectable disease exists. If metastases are detected at the time of surgical exploration, bilateral stents that may have been placed preoperatively are left in situ, and cholecystectomy is performed to prevent the subsequent development of acute cholecystitis.

Locally advanced and unresectable perihilar tumors also can be managed by means of Roux-en-Y cholecysto(docho)jejunostomy with intraoperative placement of Silastic biliary catheters or a segment III or V cholangiojejunostomy.

Midduct tumors can be managed with bile duct resection and Roux-en-Y reconstruction. Distal tumors may be amenable to Whipple resection (radical pancreaticoduodenectomy; see the image below) or pylorus-preserving pancreaticoduodenectomy. Unresectable tumors may be managed by cholecystectomy, a Roux-en-Y hepaticojejunostomy, or choledochojejunostomy proximal to the tumor, and additional gastrojejunostomy and chemical sympathectomy are considered.

Reconstruction after classic radical pancreaticodu Reconstruction after classic radical pancreaticoduodenectomy requires 3 anastomoses: pancreaticojejunostomy, choledochojejunostomy, and gastrojejunostomy. Illustration used with permission from Carol EH Scott-Conner, MD, PhD (ed), Chassin's Operative Strategy in General Surgery, Springer-Verlag, 2002.

Reconstruction involves anastomosis of bile ducts to a loop of jejunum (see the image below).

Cholangiogram showing completed choledochojejunost Cholangiogram showing completed choledochojejunostomy with widely patent anastomosis.

Laparoscopic and robotic approaches to cholangiocarcinoma have been described.


Surgical bypass is indicated in patients in whom placing a stent by means of either endoscopic or percutaneous techniques is impossible and in patients who are found to have unresectable disease or metastases at exploration.[20]

Bypass may be accomplished by performing either a Roux-en-Y hepaticojejunostomy with intraoperative placement of a Silastic transhepatic stent or a segment III bypass to the left intrahepatic ducts. In patients with distal bile duct tumors, the operation of choice is biliary enteric bypass using the upper end of the extrahepatic bile duct or gallbladder. Prophylactic gastrojejunostomy should be considered in these patients, because some of them may develop gastroduodenal obstruction prior to death. Bypass is less commonly required, because stents have improved, and even duodenal obstruction can now be effectively palliated.

Operative details

Staging of the disease is determined by evaluating the findings from computed tomography (CT) and magnetic resonance imaging (MRI).[12, 14]  Delineation of the tumor and its extent may be assessed by means of cholangiography (endoscopic and transhepatic) and magnetic resonance cholangiography.[16]  Vascular involvement can be identified and assessed by means of CT, MRI, and angiography, as previously described (see Imaging Studies).

Patient risk for surgery and anesthesia is determined, and cardiac and pulmonary assessment is performed.

If the clinical condition of the patient does not rule out surgical intervention, the resectability and extent of tumor involvement are assessed, and metastases are sought. Tumors in the lower and middle portions of the bile duct usually are resectable if angiography and venography exclude vascular invasion. Cancer of the hilar region tends to be less amenable to resection.

At surgery, further assessment is performed with intraoperative ultrasonography (US) and a search for lymph node involvement. Laparoscopy in patients with bile duct tumors can be useful in the identification of metastases and peritoneal disease and, hence, may assist in assessing resectability. Intraoperative US may be combined with laparoscopy.

Exploratory laparotomy is performed in patients who are fit for surgery and who are without any definite evidence of metastases or unresectability on preoperative investigation. One half of these patients are found to have evidence of intraperitoneal dissemination of the tumor or extensive involvement of the porta hepatis; therefore, they are candidates for minimal intervention, including bypass.

Postoperative Care

These patients are at risk for the development of general complications, including pneumonia, deep vein thrombosis (DVT), and infection. Routine perioperative antibiotic prophylaxis and coagulopathy are administered. Active physiotherapy, breathing exercises, and early ambulation are encouraged.

Complications specific to the procedure performed include anastomotic leakage and bile leakage. Stents may be placed across anastomoses and removed after cholangiography confirms the absence or healing of the leak.[37]


Postoperative complications may be general or local. General complications include the following:

Technical complications related to the procedure performed include the following:

  • Bile leakage
  • Stricture
  • Postoperative hemorrhage
  • Pancreatic fistula – May occur after radical pancreaticoduodenectomy

Complications arising from the placement of stents include the following:

  • Early - Cholangitis (7%) and perforation
  • Late - Blockage and migration of stent

Long-Term Monitoring

Patients who have evidence of positive tumor margins after resection or who develop recurrence may be candidates for adjuvant radiotherapy.[26, 27] This usually takes the form of extracorporeal therapy for positive surgical margins and intraluminal radiotherapy for positive duct margins. Chemotherapy has not been shown to be of benefit.[25]



Medication Summary

Few patients are diagnosed with early-stage resectable tumors. Guidelinesfor unresectable or metastatic disease include various chemotherapy regimens.[24]

In April 2020, the FDA approved pemigatinib, the first targeted therapy for cholangiocarcinoma with FGFR2 fusion or rearrangement.

FGFR Inhibitors

Class Summary

Inhibition of FGFR disrupts tumor cell proliferation, survival, migration, and angiogenesis.

Pemigatinib (Pemazyre)

Pemigatinib is a small molecule kinase inhibitor that targets FGFR1, 2, and 3 by inhibiting FGFR1-3 phosphorylation and signaling. Indicated for previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement as detected by an FDA-approved test.