eMedicine Specialties > General Surgery > Abdomen

Bile Duct Tumors

Todd A Nickloes, DO, Assistant Professor of Surgery, Division of Trauma/Critical Care, University of Tennessee Medical Center
Brian Reed, MD, Staff Physician, Department of Surgery, University of Tennessee Medical Center; LaMar O Mack, MD, Staff Physician, Department of Surgery, University of Tennessee Medical Center; Ravi Pokala Kiran, MBBS, MS, FRCS (Eng), FRCS (Glas), Staff Physician, Department of General Surgery, St Mary's Hospital; Naveen Pokala, MBBS, MS, FRCS, Staff Physician, Department of Surgery, Bronx Lebanon Hospital

Updated: Mar 13, 2009

Introduction

Tumors of the biliary tract (see image below and Image 1) are uncommon but serious problems. The spectrum of lesions ranges from benign tumors, such as adenomas, to malignant lesions, such as adenocarcinomas. This discussion excludes tumors of the gallbladder, which are discussed separately.

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

Cholangiography via a transhepatic or endoscopic approach is required to define the biliary anatomy and 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.

History of the Procedure

Bile duct tumors have been recognized for over a century. Musser first reported 18 cases of primary extrahepatic biliary cancer. Sako and colleagues found 570 cases of extrahepatic bile duct cancer when reviewing literature from 1935-1954. Malignancy of the intrahepatic bile ducts was described later, by Altmeir (1957); Klatskin described cancer of the hepatic duct bifurcation in 1965.

Problem

Tumors of the bile duct are rare. They constitute about 2% of all cancers found at autopsy. Benign adenomas or papillomas are exceedingly rare compared 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 hemorrhage may occur.

Cholangiocarcinomas, the most important primary tumors of the bile ducts, may involve either the intrahepatic or the extrahepatic biliary ducts. 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.

Frequency

The annual incidence of bile duct cancer in the United States is approximately 1 case per 100,000 people. In autopsy studies, the incidence varies from 0.01-0.46%.

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.

Etiology

The risk factors for bile duct cancer include the following^2,3 :

• Family history of congenital fibrosis or cysts
  • Congenital hepatic fibrosis
  • Cystic dilatation (ie, Caroli disease)
  • Choledochal cyst
  • Polycystic liver
  • Von Meyenburg complexes
• Parasitic infestations
  • 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.
  • Opisthorchis viverrini is found in Thailand, Laos, and West Malaysia.
• Gallstones and hepatolithiasis - 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.
• Primary sclerosing cholangitis (PSC) - Among patients undergoing liver transplantation for PSC, 10-30% are found to have unsuspected cholangiocarcinoma in the hepatectomy specimen. Carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 have, in combination, a sensitivity of 66% and a specificity of 100% in diagnosing cholangiocarcinoma in patients with PSC.
• Ulcerative colitis either with or without coexisting 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 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 ultrasonograms¹ of the abdomen are suspected of having cholangiocarcinoma.
• Toxic materials
  • Thorium dioxide (Thorotrast)
  • Radionuclides
  • Carcinogens (eg, arsenic, dioxin, nitrosamines, polychlorinated biphenyls)
• Drugs
  • Oral contraceptives
  • Methyldopa
  • Isoniazid
• Chronic typhoid carriers appear to have a greater incidence of hepatobiliary cancer, including cholangiocarcinoma.
• Bile duct cancers are also associated with biliary cirrhosis.

Pathophysiology

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

Pathogenesis of bile duct cancer

Long-standing 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 deoxyribonucleic acid (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 mid-duct and distal duct cholangiocarcinomas.⁵ Cholangiocarcinoma cells contain somatostatin-receptor ribonucleic acid (RNA), and cell lines have specific receptors. Cell growth is inhibited by somatostatin analogues. Cholangiocarcinomas have been detected using radionuclide scanning with a labeled somatostatin analog.

Presentation

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.

Symptoms

• Jaundice is the usual presenting symptom, followed by pruritus, which is a distinguishing feature from biliary cirrhosis. Jaundice is delayed if only 1 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.

Examination findings

• 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 common bile duct by tumor, the gallbladder may be used for bypass procedures.
• Cases with involvement of only 1 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.

Indications

Indications for bile duct tumor surgery include the following:

• The tumor is resectable. The 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 image below and Image 1).

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

Relevant Anatomy

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 as the common hepatic duct, which descends for about 1 inch before being joined by the cystic duct to form the common bile duct (CBD). The common hepatic duct lies to the right of the hepatic artery and anterior to the portal vein.

The CBD is 3 inches long and consists of 3 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, while 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, while 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 common hepatic duct
• Type II - Involvement of the bifurcation without involvement of the secondary intrahepatic ducts
• Type III a - Extends into the right secondary intrahepatic duct
• Type III b - Extends into the left secondary intrahepatic duct
• Type IV - Involvement of the secondary intrahepatic ducts on both sides

Contraindications

• Unresectable tumors - If tumors are extensive or fixed to adjoining structures, including the main portal vein or hepatic artery, they are unresectable. Cholangiogram findings 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 indicate 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

Workup

Laboratory Studies

• Liver function tests
  • Results of liver function tests are suggestive of cholestasis in patients with bile duct tumors. Fluctuations in serum levels reflect incomplete obstruction or primary involvement of only 1 hepatic duct.
  • In complete obstruction, serum bilirubin is markedly elevated. Serum alkaline phosphatase and gamma glutamyl transferase also are markedly elevated because they are markers of bile duct injury.
  • Serum aspartate aminotransferase and alanine aminotransferase, which mark hepatocellular damage, usually are only mildly elevated.
• Complete blood picture
  • Patients usually are anemic.
  • The leukocyte count may be high normal, with a preponderance of polymorphs.
• Levels of serum 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

• Ultrasonographic scanning of the liver is the investigation of first choice in patients with obstructive jaundice; these scans usually reveal dilated intrahepatic biliary ducts.¹ 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 and primary biliary cirrhosis.
• CT scans of the abdomen demonstrate intrahepatic biliary dilatation and lobar atrophy, but tumor mass may be difficult to demonstrate.⁶ Calcification may be observed. CT scanning is useful in diagnosing the level of obstruction in nearly all patients, and a specific diagnosis is possible in 78% of patients.
• Spiral CT scanning allows accurate analysis of the relationship between vascular and bile duct anatomy at the hilum.
• Magnetic resonance imaging (MRI) of the abdomen may be performed, but it adds little to ultrasonographic and CT scanning in establishing the diagnosis of extrahepatic cholangiocarcinoma.⁷
• MRI cholangiography may be valuable and is increasingly available in specialized centers.^8,9,10
• 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 defines the extent of the tumor and allows for the preoperative placement of percutaneous catheters.
  • Endoscopic retrograde cholangiopancreatography (ERCP) is of greater value in the diagnosis of distal tumors and permits the placement of endoprostheses (see image below and Image 5).¹¹
• Radiologically, cholangiocarcinomas present in 3 distinct patterns.
  • An intrahepatic mass is observed in 20-30% of cases. Calcification may be present. Ultrasonography reveals a hypoechoic, hyperechoic, or mixed echogenicity mass, whereas CT scan reveals a low-density, heterogeneous, and often peripherally enhancing mass.
  • A hilar Klatskin tumor is the most common. Ultrasonographic and CT scans 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.
  • 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.

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

Diagnostic Procedures

• Tissue diagnosis can be obtained by means of percutaneous fine-needle aspiration biopsy, brush and scrape biopsy, or cytologic examination of bile.^12,13 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 image below and Image 2); 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 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, annular 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.¹² 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 biological studies show that in addition to CEA, many tumors also stain positively for the carbohydrate antigens 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.^4,14

The diagnosis of bile duct cancers may be supported by positive findings in 2 of the 3 indicators, which are a positive reaction to CEA, nuclear size variation, and the formation of distended intracytoplasmic lumina. Neural invasion is another histologic finding that confirms a diagnosis of bile duct cancer.

Staging

Staging of bile duct tumors is performed by the (primary) tumor, (regional lymph) node, (remote) metastases (TNM) system of classification.

• T1 - Tumor limited to the mucosa or muscle layer
• T2 - Tumor invading the periductal tissue
• T3 - Tumor invading the adjacent structures
• N0 - No nodal involvement
• N2 - Involvement of regional nodes
• M0 - No distant metastases
• M1 - Presence of distant metastases

Stages are as follows:

• Stage I - T1, N0, MO
• Stage II - T2, N0, M0
• Stage III - T1-2, N1, M0
• Stage IVA - T3, N0-1, M0
• Stage IVB - T1-3, N0-1, M1

Treatment

Medical 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.¹¹ Larger, expandable metal stents, which have better patency rates than do plastic stents, include Metal-Palmaz, Strecker, Gianturco Z stent, and Wall stents.¹⁵

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 proven to be of definite benefit.¹⁶

Radiotherapy may be administered by external beam therapy; intraoperative radiotherapy using biliary stents with iridium (¹⁹² Ir), radium, or cobalt (⁶⁰ Co); radioimmunotherapy using sodium iodide (¹³¹ I) anti-CEA as a component of therapy; or charged particle irradiation. Internal radiotherapy may be combined with biliary drainage, but the value is unproven.^17,18

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

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.^19,20 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.

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 achieving negative margins are not possible with local excision, resection of the corresponding lobe is indicated.
• Type III tumors are managed best by 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 unilateral or bilateral hepaticojejunostomy, using transhepatic stents.¹⁵

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 Roux-en-Y cholecysto(docho)jejunostomy with intraoperative placement of silastic biliary catheters or a segment III or V cholangiojejunostomy.

Mid-duct tumors can be managed using bile duct resection and Roux-en-Y reconstruction. Distal tumors may be amenable to Whipple resection (radical pancreaticoduodenectomy) (see first image below and Image 3) 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 involves anastomosis of bile ducts to a loop of jejunum (see second image below and Image 4).

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.

Cholangiogram showing completed choledochojejunostomy with widely patent anastomosis.

Surgical bypass is indicated in patients in whom placing a stent by either endoscopic or percutaneous techniques is impossible and in patients who are found to have unresectable disease or metastases at exploration.¹¹

Bypass may be performed by 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. Consider prophylactic gastrojejunostomy in these patients, because some of these individuals 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.

Preoperative Details

Staging of the disease is determined by evaluating findings of CT scanning and MRI.^6,7

Delineation of the tumor and its extent may be assessed by cholangiography (endoscopic and transhepatic) and magnetic resonance cholangiography.⁹

Vascular involvement can be identified and assessed by CT scan, 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. Low and mid – bile duct tumors 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 ultrasonographic scanning and a search for lymph node involvement.

Intraoperative Details

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 ultrasonography also is useful and 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 Details

These patients are at risk for the development of general complications, including pneumonia, deep venous thrombosis, 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 leak and bile leakage. Stents may be placed across anastomoses and removed after cholangiography confirms the absence or healing of leak.¹⁵

Follow-up

Patients who have evidence of positive tumor margins after resection or who develop recurrence may be candidates for adjuvant radiotherapy.^17,18 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.¹⁶

Complications

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

• Myocardial infarction (MI)
• Pneumonia
• Surgical site infection
• Deep venous thrombosis
• Pulmonary embolism (PE)

Technical complications related to the procedure performed include the following:

• Bile leak
• 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

Outcome and Prognosis

In patients with bile duct tumors, the choice of treatment and the prognosis are influenced greatly by the location of the tumor. Prognosis is better for distal bile duct tumors, histologically differentiated, 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 gene.⁵

With hilar cholangiocarcinoma, the overall resection rate in most series varies form 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 rate (8%) than does major hepatic resection (15%), with a mean survival of 21 months compared with 24 months for major hepatic resection. No clear indication exists that survival is improved significantly by major hepatic resection when compared 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 more than 60%, and the prognosis is better than for hilar tumors, the mean survival being 39 months. The survival rate varies from 50-70% at 1 year to 17-39% at 3 years.

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.

Future and Controversies

The role of adjuvant radiotherapy and chemotherapy is controversial.^16,17,18 The use of hormones in treatment, including somatostatin analogs, 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.²¹ Therefore, preoperative radiotherapy is advocated in such patients, but the benefit has not been definitely proven.²²

Transarterial chemoembolization (TACE), infusion of 5-fluorouracil 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.²³

Liver transplantation, when performed for cholangiocarcinoma, is associated with poor survival.²⁴

Multimedia

Media file 1: Operative photograph of choledochojejunostomy, showing ample size of common duct.

Media file 2: Distal common bile duct tumor excised by radical pancreaticoduodenectomy. The tumor measured 1.2 cm in diameter.

Media file 3: 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.

Media file 4: Cholangiogram showing completed choledochojejunostomy with widely patent anastomosis.

Media file 5: Endoscopic retrograde cholangiopancreatography (ERCP) shows a narrowed area in the distal common bile duct with dilatation of the proximal biliary tree.

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Keywords

bile duct tumors, bile, bile duct, liver, pancreas, pancreatic, gall bladder, gallbladder, biliary, hepatic, cholecystectomy, cholangiocarcinoma, bile duct cancer, liver bile, biliary tree, biliary duct, biliary disease, gall bladder disease, gallbladder disease, gall bladder cancer, gallbladder cancer, bile duct symptoms, bile ducts, Klatskin tumor, cholangiocarcinoma of the hepatic duct bifurcation

Contributor Information and Disclosures

Author

Todd A Nickloes, DO, Assistant Professor of Surgery, Division of Trauma/Critical Care, University of Tennessee Medical Center
Todd A Nickloes, DO is a member of the following medical societies: American College of Osteopathic Surgeons, American Medical Association, American Osteopathic Association, Association for Academic Surgery, Eastern Association for the Surgery of Trauma, Society of Critical Care Medicine, Society of Laparoendoscopic Surgeons, Southeastern Surgical Congress, and Southern Medical Association
Disclosure: Nothing to disclose.

Coauthor(s)

Brian Reed, MD, Staff Physician, Department of Surgery, University of Tennessee Medical Center
Brian Reed, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Surgeons, and American Medical Association
Disclosure: Nothing to disclose.

LaMar O Mack, MD, Staff Physician, Department of Surgery, University of Tennessee Medical Center
LaMar O Mack, MD is a member of the following medical societies: American Urological Association, National Medical Association, and Student National Medical Association
Disclosure: Nothing to disclose.

Ravi Pokala Kiran, MBBS, MS, FRCS (Eng), FRCS (Glas), Staff Physician, Department of General Surgery, St Mary's Hospital
Disclosure: Nothing to disclose.

Naveen Pokala, MBBS, MS, FRCS, Staff Physician, Department of Surgery, Bronx Lebanon Hospital
Disclosure: Nothing to disclose.

Medical Editor

Marc D Basson, MD, PhD, MBA, Professor, Chair, Department of Surgery, Michigan State University
Marc D Basson, MD, PhD, MBA is a member of the following medical societies: American College of Surgeons and American Gastroenterological Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Michael A Grosso, MD, Consulting Staff, Department of Cardiothoracic Surgery, St Francis Hospital
Michael A Grosso, MD is a member of the following medical societies: American College of Surgeons, Society of Thoracic Surgeons, and Society of University Surgeons
Disclosure: Nothing to disclose.

CME Editor

Paolo Zamboni, MD, Professor of Surgery, Chief of Day Surgery Unit, Chair of Vascular Diseases Center, University of Ferrara, Italy
Paolo Zamboni, MD is a member of the following medical societies: American Venous Forum and New York Academy of Sciences
Disclosure: Nothing to disclose.

Chief Editor

John Geibel, MD, DSc, MA, Vice Chairman, Professor, Department of Surgery, Section of Gastrointestinal Medicine and Department of Cellular and Molecular Physiology, Yale University School of Medicine; Director of Surgical Research, Department of Surgery, Yale-New Haven Hospital
John Geibel, MD, DSc, MA is a member of the following medical societies: American Gastroenterological Association, American Physiological Society, American Society of Nephrology, Association for Academic Surgery, International Society of Nephrology, New York Academy of Sciences, and Society for Surgery of the Alimentary Tract
Disclosure: AMGEN Royalty Other

The editors wish to thank Carol E H Scott-Conner, MD, PhD, Professor, Department of Surgery, University of Iowa College of Medicine, for her previous contributions to this article.

The editors also wish to thank Richard E Glass, MBBS, MS, FRCS, Consultant General and Gastrointestinal Surgeon, Department of Gastrointestinal and General Surgery, Princess Margaret Hospital, UK, for his previous contributions to this article.

Related eMedicine topics:
Biliary Disease
Biliary Cystadenoma/Cystadenocarcinoma
Bile Duct Strictures
Biliary Obstruction
Cholangiocarcinoma [Oncology]
Cholangiocarcinoma [Radiology]
Gallbladder, Carcinoma
Gallbladder Tumors
Hepatic Adenoma
Percutaneous Gastrostomy and Jejunostomy
Postcholecystectomy Syndrome

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