Bile Duct Tumors
No Results
No Results
processing….
Tumors of the biliary tract 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.
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. 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 [1] 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:
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, [2] 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. [3] 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. [4] 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). [5]
Risk factors for bile duct cancer include the following [6, 7] :
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. [8] 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 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 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 ultrasonography [1] of the abdomen are suspected of having cholangiocarcinoma.
Toxic materials associated with an increased risk of bile duct cancer include thorium dioxide (Thorotrast), 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. [9]
The annual incidence of bile duct cancer in the United States is approximately 1 case per 100,000 people. In autopsy studies, the incidence ranges 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, 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 the P53 gene. [4]
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. [10] 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.
Smits NJ, Reeders JW. Imaging and staging of biliopancreatic malignancy: role of ultrasound. Ann Oncol. 1999. 10 Suppl 4:20-4. [Medline].
Keane MG, Pereira SP. Improving detection and treatment of liver cancer. Practitioner. 2013 Jul-Aug. 257 (1763):21-6, 2-3. [Medline].
Saurin JC, Joly-Pharaboz MO, Pernas P, Henry L, Ponchon T, Madjar JJ. Detection of Ki-ras gene point mutations in bile specimens for the differential diagnosis of malignant and benign biliary strictures. Gut. 2000 Sep. 47 (3):357-61. [Medline]. [Full Text].
Rijken AM, Offerhaus GJ, Polak MM, Gouma DJ, van Gulik TM. p53 expression as a prognostic determinant in resected distal bile duct carcinoma. Eur J Surg Oncol. 1999 Jun. 25 (3):297-301. [Medline].
Nakanuma Y, Miyata T, Uchida T. Latest advances in the pathological understanding of cholangiocarcinomas. Expert Rev Gastroenterol Hepatol. 2016. 10 (1):113-27. [Medline].
Elfaki DH, Gossard AA, Lindor KD. Cholangiocarcinoma: expanding the spectrum of risk factors. J Gastrointest Cancer. 2008. 39 (1-4):114-7. [Medline].
Chapman RW. Risk factors for biliary tract carcinogenesis. Ann Oncol. 1999. 10 Suppl 4:308-11. [Medline].
Chan-On W, Nairismägi ML, Ong CK, et al. Exome sequencing identifies distinct mutational patterns in liver fluke-related and non-infection-related bile duct cancers. Nat Genet. 2013 Dec. 45 (12):1474-8. [Medline].
Petrick JL, Yang B, Altekruse SF, Van Dyke AL, Koshiol J, Graubard BI, et al. Risk factors for intrahepatic and extrahepatic cholangiocarcinoma in the United States: A population-based study in SEER-Medicare. PLoS One. 2017. 12 (10):e0186643. [Medline]. [Full Text].
Doussot A, Groot-Koerkamp B, Wiggers JK, Chou J, Gonen M, DeMatteo RP, et al. Outcomes after Resection of Intrahepatic Cholangiocarcinoma: External Validation and Comparison of Prognostic Models. J Am Coll Surg. 2015 Aug. 221 (2):452-61. [Medline].
Freeny PC. Computed tomography in the diagnosis and staging of cholangiocarcinoma and pancreatic carcinoma. Ann Oncol. 1999. 10 Suppl 4:12-7. [Medline].
Tani K, Kubota Y, Yamaguchi T, Kitagawa S, Katoh T, Seki T, et al. MR imaging of peripheral cholangiocarcinoma. J Comput Assist Tomogr. 1991 Nov-Dec. 15 (6):975-8. [Medline].
Kim HJ, Lee JM, Kim SH, Han JK, Lee JY, Choi JY, et al. Evaluation of the longitudinal tumor extent of bile duct cancer: value of adding gadolinium-enhanced dynamic imaging to unenhanced images and magnetic resonance cholangiography. J Comput Assist Tomogr. 2007 May-Jun. 31 (3):469-74. [Medline].
Hänninen EL, Pech M, Jonas S, Ricke J, Thelen A, Langrehr J, et al. Magnetic resonance imaging including magnetic resonance cholangiopancreatography for tumor localization and therapy planning in malignant hilar obstructions. Acta Radiol. 2005 Aug. 46 (5):462-70. [Medline].
Sakai Y, Tsuyuguchi T, Tsuchiya S, Fukuda Y, Miyakawa K, Sugiyama H, et al. Clinical utility of peroral cholangioscopy for mucin-producing bile duct tumor. Hepatogastroenterology. 2008 Sep-Oct. 55 (86-87):1509-12. [Medline].
Han NY, Kim JY, Kim MJ, Park BJ, Sung DJ, Sim KC, et al. Validation of Feasibility of Magnetic Resonance Imaging for the Measurement of Depth of Tumor Invasion in Distal Bile Duct Cancer According to the New American Joint Committee on Cancer Staging System. Acad Radiol. 2017 Dec. 24 (12):1526-1534. [Medline].
Choi JH, Lee SK. Percutaneous transhepatic cholangioscopy: does its role still exist?. Clin Endosc. 2013 Sep. 46 (5):529-36. [Medline]. [Full Text].
Rumalla A, Baron TH. Evaluation and endoscopic palliation of cholangiocarcinoma. Management of cholangiocarcinoma. Dig Dis. 1999. 17 (4):194-200. [Medline].
Desa LA, Akosa AB, Lazzara S, Domizio P, Krausz T, Benjamin IS. Cytodiagnosis in the management of extrahepatic biliary stricture. Gut. 1991 Oct. 32 (10):1188-91. [Medline]. [Full Text].
Furmanczyk PS, Grieco VS, Agoff SN. Biliary brush cytology and the detection of cholangiocarcinoma in primary sclerosing cholangitis: evaluation of specific cytomorphologic features and CA19-9 levels. Am J Clin Pathol. 2005 Sep. 124 (3):355-60. [Medline]. [Full Text].
Lamerz R. Role of tumour markers, cytogenetics. Ann Oncol. 1999. 10 Suppl 4:145-9. [Medline].
[Guideline] NCCN Clinical Practice Guidelines in Oncology: Hepatobiliary Cancers. Version 2.2017. National Comprehensive Cancer Network. Available at https://www.nccn.org/professionals/physician_gls/PDF/hepatobiliary.pdf. May 25, 2017; Accessed: December 7, 2017.
Todoroki T. Chemotherapy for bile duct carcinoma in the light of adjuvant chemotherapy to surgery. Hepatogastroenterology. 2000 May-Jun. 47 (33):644-9. [Medline].
Oh D, Lim DH, Heo JS, Choi SH, Choi DW, Ahn YC, et al. The role of adjuvant radiotherapy in microscopic tumor control after extrahepatic bile duct cancer surgery. Am J Clin Oncol. 2007 Feb. 30 (1):21-5. [Medline].
Pitt HA, Nakeeb A, Abrams RA, Coleman J, Piantadosi S, Yeo CJ, et al. Perihilar cholangiocarcinoma. Postoperative radiotherapy does not improve survival. Ann Surg. 1995 Jun. 221 (6):788-97; discussion 797-8. [Medline]. [Full Text].
Ferrero A, Lo Tesoriere R, Viganò L, Caggiano L, Sgotto E, Capussotti L. Preoperative biliary drainage increases infectious complications after hepatectomy for proximal bile duct tumor obstruction. World J Surg. 2009 Feb. 33 (2):318-25. [Medline].
Gerhards MF, Gonzalez DG, ten Hoopen-Neumann H, van Gulik TM, de Wit LT, Gouma DJ. Prevention of implantation metastases after resection of proximal bile duct tumours with pre-operative low dose radiation therapy. Eur J Surg Oncol. 2000 Aug. 26 (5):480-5. [Medline].
Ortner MA. Photodynamic therapy of cholangiocarcinoma cancer. Gastrointest Endosc Clin N Am. 2000 Jul. 10 (3):481-6. [Medline].
Smith I, Kahaleh M. Biliary Tumor Ablation with Photodynamic Therapy and Radiofrequency Ablation. Gastrointest Endosc Clin N Am. 2015 Oct. 25 (4):793-804. [Medline].
Jeyarajah DR, Klintmalm GB. Is liver transplantation indicated for cholangiocarcinoma?. J Hepatobiliary Pancreat Surg. 1998. 5 (1):48-51. [Medline].
Kawamoto H, Ishida E, Okamoto Y, Okada H, Sakaguchi K, Nakagawa M, et al. Evaluation of covered metallic stents in malignant biliary stenosis–prominent effectiveness in gallbladder carcinoma. Hepatogastroenterology. 2005 Sep-Oct. 52 (65):1351-6. [Medline].
Saleem A, Leggett CL, Murad MH, Baron TH. Meta-analysis of randomized trials comparing the patency of covered and uncovered self-expandable metal stents for palliation of distal malignant bile duct obstruction. Gastrointest Endosc. 2011 Aug. 74 (2):321-327.e1-3. [Medline].
Schinzari G, Rossi E, Mambella G, Strippoli A, Cangiano R, Mutignani M, et al. First-line Treatment of Advanced Biliary Ducts Carcinoma: A Randomized Phase II Study Evaluating 5-FU/LV Plus Oxaliplatin (Folfox 4) Versus 5-FU/LV (de Gramont Regimen). Anticancer Res. 2017 Sep. 37 (9):5193-5197. [Medline]. [Full Text].
Kosuge T, Yamamoto J, Shimada K, Yamasaki S, Makuuchi M. Improved surgical results for hilar cholangiocarcinoma with procedures including major hepatic resection. Ann Surg. 1999 Nov. 230 (5):663-71. [Medline]. [Full Text].
Havlik R, Sbisà E, Tullo A, Kelly MD, Mitry RR, Jiao LR, et al. Results of resection for hilar cholangiocarcinoma with analysis of prognostic factors. Hepatogastroenterology. 2000 Jul-Aug. 47 (34):927-31. [Medline].
Levi Sandri GB, Spoletini G, Mascianà G, Colasanti M, Lepiane P, Vennarecci G, et al. The role of minimally invasive surgery in the treatment of cholangiocarcinoma. Eur J Surg Oncol. 2017 Sep. 43 (9):1617-1621. [Medline].
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.
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.
Ravi Pokala Kiran, MBBS, MS, FRCS
Disclosure: Nothing to disclose.
Naveen Pokala, MBBS, MS, FRCS
Disclosure: Nothing to disclose.
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.
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: Nothing to disclose.
Marc D Basson, MD, PhD, MBA, FACS Senior Associate Dean for Medicine and Research, Professor of Surgery, Pathology, and Biomedical Sciences, 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.
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.
Bile Duct Tumors
Research & References of Bile Duct Tumors|A&C Accounting And Tax Services
Source
0 Comments