Bile Duct Tumors Workup

  • Author: Todd A Nickloes, DO, FACOS; Chief Editor: John Geibel, MD, DSc, MSc, AGAF  more...
 
Updated: Nov 18, 2015
 

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 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.

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.

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Imaging Studies

Ultrasonography

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 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.[10] 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.

Magnetic resonance imaging

Magnetic resonance imaging (MRI) of the abdomen may be performed, but it adds little to ultrasonography and CT with respect to establishing the diagnosis of extrahepatic cholangiocarcinoma.[11]  MRI cholangiography may be valuable and is increasingly available in specialized centers.[12, 13, 14]

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.[15]

Endoscopic retrograde cholangiopancreatography (ERCP) is of greater value in the diagnosis of distal tumors and permits the placement of endoprostheses (see the image below).[16]

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. Ultrasonography 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. Ultrasonography 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.

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Tissue Diagnosis

Tissue diagnosis can be obtained by means of percutaneous fine-needle aspiration (FNA) biopsy, brush-and-scrape biopsy, or cytologic examination of bile.[17, 18] 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.

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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, 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.[17] 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.[3, 19]

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.

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Staging

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[20] :

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

For more information, see Biliary Tract Cancer Staging.

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Contributor Information and Disclosures
Author

Todd A Nickloes, DO, FACOS Associate Professor, Department of Surgery, Division of Trauma/Critical Care, University of Tennessee Medical Center-Knoxville

Todd A Nickloes, DO, FACOS is a member of the following medical societies: American Medical Association, American Osteopathic Association, Association for Academic Surgery, Society of Critical Care Medicine, Society of Laparoendoscopic Surgeons, Southeastern Surgical Congress, Southern Medical Association, Eastern Association for the Surgery of Trauma, American College of Osteopathic Surgeons

Disclosure: Nothing to disclose.

Coauthor(s)

Ravi Pokala Kiran, MBBS, MS, FRCS 

Disclosure: Nothing to disclose.

Naveen Pokala, MBBS, MS, FRCS 

Disclosure: Nothing to disclose.

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, American Medical Association

Disclosure: Nothing to disclose.

LaMar O Mack, MD Resident 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, Student National Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

John Geibel, MD, DSc, MSc, AGAF Vice Chair and Professor, Department of Surgery, Section of Gastrointestinal Medicine, Professor, Department of Cellular and Molecular Physiology, Yale University School of Medicine; Director of Surgical Research, Department of Surgery, Yale-New Haven Hospital; American Gastroenterological Association Fellow

John Geibel, MD, DSc, MSc, AGAF 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, Society for Surgery of the Alimentary Tract

Disclosure: Received royalty from AMGEN for consulting; Received ownership interest from Ardelyx for consulting.

Additional Contributors

Marc D Basson, MD, PhD, MBA, FACS Associate Dean for Medicine, Professor of Surgery and Basic Science, University of North Dakota School of Medicine and Health Sciences

Marc D Basson, MD, PhD, MBA, FACS is a member of the following medical societies: Alpha Omega Alpha, American College of Surgeons, American Gastroenterological Association, Phi Beta Kappa, Sigma Xi

Disclosure: Nothing to disclose.

Acknowledgements

Richard E Glass, MBBS, MS, FRCS Consultant General and Gastrointestinal Surgeon, Department of Gastrointestinal and General Surgery, Princess Margaret Hospital, UK

Disclosure: Nothing to disclose.

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.

Carol EH Scott-Conner, MD, PhD Professor, Department of Surgery, University of Iowa College of Medicine

Carol Eh Scott-Conner is a member of the following medical societies: American Association for Cancer Research, American Association for the Surgery of Trauma, American Burn Association, American Cancer Society, American College of Gastroenterology, American College of Surgeons, American Medical Association, American Society for Gastrointestinal Endoscopy, Association for Academic Surgery, Association for Surgical Education,Association of VA Surgeons, Iowa Medical Society, Sigma Xi, Society for Surgery of the Alimentary Tract, Society of American Gastrointestinal and Endoscopic Surgeons, Society of Critical Care Medicine, Society of Surgical Oncology, Society of University Surgeons, and Southeastern Surgical Congress

Disclosure: Nothing to disclose.

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Operative photograph of choledochojejunostomy, showing ample size of common duct.
Distal common bile duct tumor excised by radical pancreaticoduodenectomy. The tumor measured 1.2 cm in diameter.
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.
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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