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| {{Cholangiocarcinoma}} | | {{Cholangiocarcinoma}} |
| {{CMG}} | | {{CMG}}; {{AE}}{{F.K}} [mailto:fkahe@bidmc.harvard.edu] [mailto:fkahe@bidmc.harvard.edu], {{PSK}} |
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| ==Overview== | | ==Overview== |
| '''Cholangiocarcinoma''' is a [[cancer]] of the [[bile duct]]s, which drain [[bile]] from the [[liver]] into the [[small intestine]]. Cholangiocarcinoma is a malignant tumor arising from cholangiocytes in the biliary tree.<ref name=radio>Cholangiocarcinoma. Radiopaedia. http://radiopaedia.org/articles/cholangiocarcinoma</ref>
| | Cholangiocarcinoma refers to the malignant tumor of bile ducts. The [[epithelial cell]] lining the [[bile ducts]] are called [[cholangiocytes]]. The malignant transformsation of [[cholangiocytes]] leads to cholangiocarcinoma. [[Malignant]] [[transformation]] of [[cholangiocytes]] into cholangiocarcinoma include [[hyperplasia]], [[metaplasia]] and dysplasia. Biliary intraepithelial [[neoplasia]] is believed to be the initial lesion of cholangiocarcinoma, particularly in patients with [[hepatolithiasis]] in [[bile ducts]]. On the basis of location, cholangiocarcinoma may be classified into extrahepatic cholangiocarcinoma, perihilar cholangiocarcinoma, and intrahepatic cholangiocarcinoma. Cholangiocarcinoma must be differentiated from other diseases that cause [[jaundice]], [[abdominal pain]], [[weight loss]], and [[fatigue]], such as [[gallbladder cancer]], [[hepatocellular carcinoma]], [[pancreatic cancer]], [[cholecystitis]], and choledochitis. Common complications of cholangiocarcinoma include [[infection]], [[liver failure]], and [[Metastasis|tumor metastasis]]. Prognosis is generally poor, and the survival rate of patients with cholangiocarcinoma mainly depends on extent of the [[tumor]] and resectability. The common symptoms of cholangiocarcinoma include [[jaundice]], [[pruritis]], [[abdominal pain]], [[weight loss]]. Common physical examination findings of cholangiocarcinoma include [[jaundice]], icteric sclera, [[hepatomegaly]], right upper quadrant mass, and [[Gall bladder|palpable gall bladder]]. The mainstay of treatment for cholangiocarcinoma is surgical resection. Surgical resection of tumors with negative margins is the best option for all subtypes of cholangiocarcinoma. Chemotherapy is indicated for unresectable cholangiocarcinoma as [[palliation|palliative chemotherapy]]. Chemotherapy agents used to treat cholangiocarcinoma include [[5-fluorouracil]], [[gemcitabine]], [[irinotecan]], [[cisplatin]], or [[doxorubicin]]. |
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| ==Classification== | | ==Classification== |
| Cholangiocarcinoma may be classified according to location of the tumor into three subtypes: extrahepatic bile duct cancer, perihilar bile duct cancer, and intrahepatic bile duct cancer.<ref>{{cite journal |author=KLATSKIN G |title=ADENOCARCINOMA OF THE HEPATIC DUCT AT ITS BIFURCATION WITHIN THE PORTA HEPATIS. AN UNUSUAL TUMOR WITH DISTINCTIVE CLINICAL AND PATHOLOGICAL FEATURES |journal=Am J Med |volume=38 |issue= |pages=241-56 |year= |pmid=14256720}}</ref> Perihilar cholangiocarcinoma may be classified according to Bismuth-Corlette classification into five subtypes based on the extent of ductal infiltration. | | Cholangiocarcinoma may be classified according to location of the tumor into three subtypes such as extrahepatic bile duct cancer, perihilar bile duct cancer, and intrahepatic [[bile duct]] cancer. Perihilar cholangiocarcinoma may be classified according to Bismuth-Corlette classification into five subtypes based on the extent of ductal infiltration. |
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| ==Epidemiology and Demographics== | | ==Pathophysiology== |
| It is a relatively rare cancer, with an annual [[incidence (epidemiology)|incidence]] of 1–2 cases per 100,000 in the Western world,<ref name="Landis">{{cite journal |author=Landis S, Murray T, Bolden S, Wingo P |title=Cancer statistics, 1998 |journal=CA Cancer J Clin |volume=48 |issue=1 |pages=6–29 |year= |id=PMID 9449931}}</ref> but rates of cholangiocarcinoma have been rising worldwide over the past several decades.<ref name="rising">{{cite journal |author=Patel T |title=Worldwide trends in mortality from biliary tract malignancies |journal=BMC Cancer |volume=2 |issue= |pages=10 |year= |id=PMID 11991810}}</ref>
| | The [[epithelial cell]] lining the [[bile ducts]] are called [[cholangiocytes]]. The malignant transformsation of [[cholangiocytes]] leads to cholangiocarcinoma. [[Malignant]] [[transformation]] of [[cholangiocytes]] into cholangiocarcinoma include [[hyperplasia]], [[metaplasia]] and dysplasia. Biliary intraepithelial [[neoplasia]] is believed to be the initial lesion of cholangiocarcinoma, particularly in patients with [[hepatolithiasis]] in [[bile ducts]]. |
| ==Risk factors==
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| Risk factors for cholangiocarcinoma include [[primary sclerosing cholangitis]] (an inflammatory disease of the bile ducts), congenital liver malformations, infection with the parasitic [[liver fluke]]s ''[[Opisthorchis viverrini]]'' or ''[[Clonorchis sinensis]]'', and exposure to [[Thorotrast]] ([[thorium dioxide]]), a chemical previously used in [[medical imaging]].
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| ==Diagnosis==
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| The symptoms of cholangiocarcinoma include [[jaundice]], [[weight loss]], and sometimes [[pruritis|generalized itching]]. The disease is diagnosed through a combination of [[blood test]]s, imaging, [[endoscopy]], and sometimes surgical exploration.
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| Cholangiocarcinoma is definitively diagnosed from tissue, i.e. it is proven by biopsy or examination of the tissue excised at surgery. It may be suspected in a patient with [[jaundice#post-hepatic|obstructive jaundice]]. Considering it as the working-diagnosis may be challenging in patients with primary sclerosing cholangitis (PSC); such patients are at high risk of developing cholangiocarcinoma, but the symptoms may be difficult to distinguish from those of PSC. Furthermore, in patients with PSC, such diagnostic clues as a visible mass on imaging or biliary ductal dilatation may not be evident.
| | ==Causes== |
| ==Treatment== | | There are no established causes for cholangiocarcinoma. |
| Surgery is the only potentially curative treatment, but most patients have advanced and inoperable disease at the time of diagnosis. After surgery, [[adjuvant#oncology|adjuvant]] [[chemotherapy]] or [[radiation therapy]] may be given to increase the chances of cure. Patients with advanced and inoperable cholangiocarcinoma are generally treated with chemotherapy and [[palliative care]] measures. Areas of ongoing [[medical research]] in cholangiocarcinoma include the use of newer [[targeted therapy|targeted therapies]] (such as [[erlotinib]]) and the use of [[photodynamic therapy]].
| | ==Differential Diagnosis== |
| | Cholangiocarcinoma must be differentiated from other diseases that cause [[jaundice]], [[abdominal pain]], [[weight loss]], and [[fatigue]], such as [[gallbladder cancer]], [[hepatocellular carcinoma]], [[pancreatic cancer]], [[cholecystitis]], and choledochitis. |
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| Cholangiocarcinoma is considered curable only by [[resection|surgical removal]]. Without surgery, it is a rapidly fatal disease with 5-year survival rates of less than 5%.<ref>{{cite journal |author=Farley D, Weaver A, Nagorney D |title="Natural history" of unresected cholangiocarcinoma: patient outcome after noncurative intervention |journal=Mayo Clin Proc |volume=70 |issue=5 |pages=425-9 |year=1995 |pmid=7537346}}</ref> Often, the operability of the tumor can only be assessed at the time of surgery;<ref>{{cite journal |author=Su C, Tsay S, Wu C, Shyr Y, King K, Lee C, Lui W, Liu T, P'eng F |title=Factors influencing postoperative morbidity, mortality, and survival after resection for hilar cholangiocarcinoma |journal=Ann Surg |volume=223 |issue=4 |pages=384-94 |year=1996 |pmid=8633917}}</ref> therefore, most patients undergo exploratory surgery unless there is a clear-cut indication that the tumor is inoperable.
| | ==Epidemiology and Demographics== |
| | The [[incidence]] of cholangiocarcinoma is approximately 1-2 per 100,000 individuals in the United States. The [[prevalence]] of cholangiocarcinoma is approximately 0.01% to 0.46% per 100,000 individuals. Patients of all age groups may develop cholangiocarcinoma. Cholangiocarcinoma is more common in males than in females. |
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| Adjuvant therapy followed by [[liver transplantation]] may have a role in treatment of certain unresectable cases.<ref> Heimbach JK, Gores GJ, Haddock MG, et al, Predictors of disease recurrence following neoadjuvant chemoradiotherapy and liver transplantation for unresectable perihilar cholangiocarcinoma, Transplantation. 2006 Dec 27;82(12):1703-7.</ref>
| | ==Risk Factors== |
| | Common risk factors in the development of cholangiocarcinoma are chronic inflammatory conditions of bile duct, [[liver fluke]] infections, [[choledochal cysts]], toxins, and viral infections. |
| | ==Screening== |
| | According to the the U.S. Preventive Service Task Force (USPSTF), there is insufficient evidence to recommend routine screening for cholangiocarcinoma. |
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| ==References== | | ==Natural history, Complications and Prognosis== |
| {{reflist|2}}
| | Common complications of cholangiocarcinoma include [[infection]], [[liver failure]], and [[Metastasis|tumor metastasis]]. Prognosis is generally poor, and the survival rate of patients with cholangiocarcinoma mainly depends on extent of the tumor and resectability. Even with resection, prognosis is poor with 5-year survival of only 10-44%. The presence of [[primary sclerosing cholangitis]] is associated with a particularly poor prognosis among patients with cholangiocarcinoma. |
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| ==Additional Reading== | | ==Diagnosis== |
| {{refbegin|2}}
| | ===Staging=== |
| 1. Landis S, Murray T, Bolden S, Wingo P. "Cancer statistics, 1998". CA Cancer J Clin 48 (1): 6–29. PMID 9449931.
| | The staging of cholangiocarcinoma varies depending on whether the tumor is primarily intrahepatic (ICC), hilar/perihilar (Klatskin), or extrahepatic. Current staging classifications of intrahepatic cholangiocarcinoma include UICC system, Okabayashi system, and AJCC system. Current staging classifications of perihilar cholangiocarcinoma include MSKCC system and AJCC system. |
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| 2. Patel T. "Worldwide trends in mortality from biliary tract malignancies". BMC Cancer 2: 10. PMID 11991810.
| | ===History and Symptoms=== |
| | The common symptoms of cholangiocarcinoma include [[jaundice]], [[pruritis]], [[abdominal pain]], [[weight loss]]. |
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| 3. Nagorney D, Donohue J, Farnell M, Schleck C, Ilstrup D (1993). "Outcomes after curative resections of cholangiocarcinoma". Arch Surg 128 (8): 871–7; discussion 877-9. PMID 8393652.
| | ===Physical Examination=== |
| | Common physical examination findings of cholangiocarcinoma include [[jaundice]], icteric sclera, [[hepatomegaly]], right upper quadrant mass, and [[Gall bladder|palpable gall bladder]]. |
| | ===Laboratory Findings=== |
| | Laboratory tests for cholangiocarcinoma include [[aspartate aminotransferase]] (AST) and [[alanine aminotransferase]] (ALT), [[prothrombin time]], [[albumin]] and total protein, [[bilirubin]], [[lactate dehydrogenase|L-Lactate dehydrogenase]] and [[alkaline phosphatase]]. |
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| 4. Nakeeb A, Pitt H, Sohn T, Coleman J, Abrams R, Piantadosi S, Hruban R, Lillemoe K, Yeo C, Cameron J (1996). "Cholangiocarcinoma. A spectrum of intrahepatic, perihilar, and distal tumors". Ann Surg 224 (4): 463–73; discussion 473-5. PMID 8857851.
| | ===CT=== |
| | On [[Computed tomography|CT scan]], cholangiocarcinoma is characterized by homogenously low in attenuation and demonstrate heterogenous minor peripheral enhancement with gradual enhancement centrally. Capsular retraction may be observed. [[Bile ducts]] distal to the mass are typically dilated. |
| | ===MRI=== |
| | On [[Magnetic resonance imaging|MRI]], cholangiocarcinoma is characterized by either isointense or hypointense relative to the normal liver on T1 and mildly to markedly hyperintense on T2. Moderate to incomplete enhancement is observed on contrast [[MRI]]. |
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| 5.Feldman, pp. 1493–1496.
| | ===Abdominal Ultrasound=== |
| | On abdominal [[ultrasound]], cholangiocarcinoma is characterized by obstruction and dilation of [[bile ducts]]. Mass-forming intrahepatic cholangiocarcinoma is characterized by homogeneous mass of intermediate echogenicity with a peripheral hypoechoic halo of compressed liver. Periductal infiltrating intrahepatic cholangiocarcinoma is characterized by capsular retraction. Intraductal cholangiocarcinoma is characterized by alterations in duct caliber, usually duct ectasia with or without a visible mass. |
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| 6. Khan S, Taylor-Robinson S, Toledano M, Beck A, Elliott P, Thomas H (2002). "Changing international trends in mortality rates for liver, biliary and pancreatic tumours". J Hepatol 37 (6): 806-13. PMID 12445422.
| | ===Other Imaging Findings=== |
| | Other imaging studies for cholangiocarcinoma include [[endoscopic retrograde cholangiopancreatography]], [[endoscopic ultrasound]], [[percutaneous transhepatic cholangiography]], and [[MRCP]]. |
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| 7. Vauthey J, Blumgart L (1994). "Recent advances in the management of cholangiocarcinomas". Semin Liver Dis 14 (2): 109-14. PMID 8047893.
| | ===Other Diagnostic Studies=== |
| | No additional tests are recommended for the diagnosis of cholangiocarcinoma. |
| | ==Treatment== |
| | ===Medical Therapy=== |
| | [[Chemotherapy]] is indicated for unresectable cholangiocarcinoma as [[palliation|palliative chemotherapy]]. [[Chemotherapy]] agents used to treat cholangiocarcinoma include [[5-fluorouracil]], [[gemcitabine]], [[irinotecan]], [[cisplatin]], or [[doxorubicin]]. |
| | ===Surgery=== |
| | The mainstay of treatment for cholangiocarcinoma is surgical resection. Surgical resection of tumors with negative margins is the best option for all subtypes of cholangiocarcinoma. |
| | ===Prevention=== |
| | Effective measures for the primary prevention of cholangiocarcinoma [[hepatitis B]] [[vaccination]], weight reduction, avoiding excess alcohol use. |
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| 8.Henson D, Albores-Saavedra J, Corle D (1992). "Carcinoma of the extrahepatic bile ducts. Histologic types, stage of disease, grade, and survival rates". Cancer 70 (6): 1498-501. PMID 1516001.
| | ==References== |
| | | {{reflist|2}} |
| 9. Rosen C, Nagorney D, Wiesner R, Coffey R, LaRusso N (1991). "Cholangiocarcinoma complicating primary sclerosing cholangitis". Ann Surg 213 (1): 21-5. PMID 1845927.
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| 10. Multiple independent studies have documented a steady increase in the worldwide incidence of cholangiocarcinoma. Some relevant journal articles include:
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| *Patel T. "Worldwide trends in mortality from biliary tract malignancies". BMC Cancer 2: 10. PMID 11991810.
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| * Patel T (2001). "Increasing incidence and mortality of primary intrahepatic cholangiocarcinoma in the United States". Hepatology 33 (6): 1353–7. PMID 11391522.
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| * Shaib Y, Davila J, McGlynn K, El-Serag H (2004). "Rising incidence of intrahepatic cholangiocarcinoma in the United States: a true increase?". J Hepatol 40 (3): 472-7. PMID 15123362.
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| * West J, Wood H, Logan R, Quinn M, Aithal G (2006). "Trends in the incidence of primary liver and biliary tract cancers in England and Wales 1971–2001". Br J Cancer 94 (11): 1751–8. PMID 16736026.
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| * Khan S, Taylor-Robinson S, Toledano M, Beck A, Elliott P, Thomas H (2002). "Changing international trends in mortality rates for liver, biliary and pancreatic tumours". J Hepatol 37 (6): 806-13. PMID 12445422.
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| * Welzel T, McGlynn K, Hsing A, O'Brien T, Pfeiffer R (2006). "Impact of classification of hilar cholangiocarcinomas (Klatskin tumors) on the incidence of intra- and extrahepatic cholangiocarcinoma in the United States". J Natl Cancer Inst 98 (12): 873-5. PMID 16788161.
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| 11. Shaib Y, El-Serag H, Davila J, Morgan R, McGlynn K (2005). "Risk factors of intrahepatic cholangiocarcinoma in the United States: a case-control study". Gastroenterology 128 (3): 620-6. PMID 15765398.
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| 12.Chapman R. "Risk factors for biliary tract carcinogenesis". Ann Oncol 10 Suppl 4: 308-11. PMID 10436847.
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| 13.Epidemiologic studies which have addressed the incidence of cholangiocarcinoma in people with primary sclerosing cholangitis include the following:
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| * Bergquist A, Ekbom A, Olsson R, Kornfeldt D, Lööf L, Danielsson A, Hultcrantz R, Lindgren S, Prytz H, Sandberg-Gertzén H, Almer S, Granath F, Broomé U (2002). "Hepatic and extrahepatic malignancies in primary sclerosing cholangitis". J Hepatol 36 (3): 321-7. PMID 11867174.
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| * Bergquist A, Glaumann H, Persson B, Broomé U (1998). "Risk factors and clinical presentation of hepatobiliary carcinoma in patients with primary sclerosing cholangitis: a case-control study". Hepatology 27 (2): 311-6. PMID 9462625.
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| * Burak K, Angulo P, Pasha T, Egan K, Petz J, Lindor K (2004). "Incidence and risk factors for cholangiocarcinoma in primary sclerosing cholangitis". Am J Gastroenterol 99 (3): 523-6. PMID 15056096.
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| 14.Watanapa P (1996). "Cholangiocarcinoma in patients with opisthorchiasis". Br J Surg 83 (8): 1062–64. PMID 8869303.
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| 15.Watanapa P, Watanapa W (2002). "Liver fluke-associated cholangiocarcinoma". Br J Surg 89 (8): 962-70. PMID 12153620.
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| 16.Shin H, Lee C, Park H, Seol S, Chung J, Choi H, Ahn Y, Shigemastu T (1996). "Hepatitis B and C virus, Clonorchis sinensis for the risk of liver cancer: a case-control study in Pusan, Korea". Int J Epidemiol 25 (5): 933-40. PMID 8921477.
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| 17.Kobayashi M, Ikeda K, Saitoh S, Suzuki F, Tsubota A, Suzuki Y, Arase Y, Murashima N, Chayama K, Kumada H (2000). "Incidence of primary cholangiocellular carcinoma of the liver in Japanese patients with hepatitis C virus-related cirrhosis". Cancer 88 (11): 2471–7. PMID 10861422.
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| 18. Yamamoto S, Kubo S, Hai S, Uenishi T, Yamamoto T, Shuto T, Takemura S, Tanaka H, Yamazaki O, Hirohashi K, Tanaka T (2004). "Hepatitis C virus infection as a likely etiology of intrahepatic cholangiocarcinoma". Cancer Sci 95 (7): 592-5. PMID 15245596.
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| 19.Lu H, Ye M, Thung S, Dash S, Gerber M (2000). "Detection of hepatitis C virus RNA sequences in cholangiocarcinomas in Chinese and American patients". Chin Med J (Engl) 113 (12): 1138–41. PMID 11776153.
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| 20. Sorensen H, Friis S, Olsen J, Thulstrup A, Mellemkjaer L, Linet M, Trichopoulos D, Vilstrup H, Olsen J (1998). "Risk of liver and other types of cancer in patients with cirrhosis: a nationwide cohort study in Denmark". Hepatology 28 (4): 921-5. PMID 9755226.
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| 21.Lipsett P, Pitt H, Colombani P, Boitnott J, Cameron J (1994). "Choledochal cyst disease. A changing pattern of presentation". Ann Surg 220 (5): 644-52. PMID 7979612.
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| 22. Dayton M, Longmire W, Tompkins R (1983). "Caroli's Disease: a premalignant condition?". Am J Surg 145 (1): 41-8. PMID 6295196.
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| 23. Mecklin J, Järvinen H, Virolainen M (1992). "The association between cholangiocarcinoma and hereditary nonpolyposis colorectal carcinoma". Cancer 69 (5): 1112–4. PMID 1310886.
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| 24.Lee S, Kim M, Lee S, Jang S, Song M, Kim K, Kim H, Seo D, Song D, Yu E, Lee S, Min Y (2004). "Clinicopathologic review of 58 patients with biliary papillomatosis". Cancer 100 (4): 783-93. PMID 14770435.
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| 25.Lee C, Wu C, Chen G (2002). "What is the impact of coexistence of hepatolithiasis on cholangiocarcinoma?". J Gastroenterol Hepatol 17 (9): 1015–20. PMID 12167124.
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| 26. Su C, Shyr Y, Lui W, P'Eng F (1997). "Hepatolithiasis associated with cholangiocarcinoma". Br J Surg 84 (7): 969-73. PMID 9240138.
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| 27. Donato F, Gelatti U, Tagger A, Favret M, Ribero M, Callea F, Martelli C, Savio A, Trevisi P, Nardi G (2001). "Intrahepatic cholangiocarcinoma and hepatitis C and B virus infection, alcohol intake, and hepatolithiasis: a case-control study in Italy". Cancer Causes Control 12 (10): 959-64. PMID 11808716.
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| 28.Sahani D, Prasad S, Tannabe K, Hahn P, Mueller P, Saini S. "Thorotrast-induced cholangiocarcinoma: case report". Abdom Imaging 28 (1): 72-4. PMID 12483389.
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| 29. Zhu A, Lauwers G, Tanabe K (2004). "Cholangiocarcinoma in association with Thorotrast exposure". J Hepatobiliary Pancreat Surg 11 (6): 430-3. PMID 15619021.
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| 30.KLATSKIN G. "ADENOCARCINOMA OF THE HEPATIC DUCT AT ITS BIFURCATION WITHIN THE PORTA HEPATIS. AN UNUSUAL TUMOR WITH DISTINCTIVE CLINICAL AND PATHOLOGICAL FEATURES". Am J Med 38: 241-56. PMID 14256720.
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| 31. Roskams T (2006). "Liver stem cells and their implication in hepatocellular and cholangiocarcinoma". Oncogene 25 (27): 3818–22. PMID 16799623.
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| 32.Liu C, Wang J, Ou Q (2004). "Possible stem cell origin of human cholangiocarcinoma". World J Gastroenterol 10 (22): 3374–6. PMID 15484322.
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| 33. Sell S, Dunsford H (1989). "Evidence for the stem cell origin of hepatocellular carcinoma and cholangiocarcinoma". Am J Pathol 134 (6): 1347–63. PMID 2474256.
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| 34. Sirica A (2005). "Cholangiocarcinoma: molecular targeting strategies for chemoprevention and therapy". Hepatology 41 (1): 5–15. PMID 15690474.
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| 35. Holzinger F, Z'graggen K, Büchler M. "Mechanisms of biliary carcinogenesis: a pathogenetic multi-stage cascade towards cholangiocarcinoma". Ann Oncol 10 Suppl 4: 122-6. PMID 10436802.
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| 36.Gores G (2003). "Cholangiocarcinoma: current concepts and insights". Hepatology 37 (5): 961-9. PMID 12717374.
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| 37. de Groen P, Gores G, LaRusso N, Gunderson L, Nagorney D (1999). "Biliary tract cancers". N Engl J Med 341 (18): 1368–78. PMID 10536130.
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| 38. Henson D, Albores-Saavedra J, Corle D (1992). "Carcinoma of the extrahepatic bile ducts. Histologic types, stage of disease, grade, and survival rates". Cancer 70 (6): 1498-501. PMID 1516001.
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| 39. Studies of the performance of serum markers for cholangiocarcinoma (such as carcinoembryonic antigen and CA19-9) in patients with and without primary sclerosing cholangitis include the following:
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| * Nehls O, Gregor M, Klump B (2004). "Serum and bile markers for cholangiocarcinoma". Semin Liver Dis 24 (2): 139-54. PMID 15192787.
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| * Siqueira E, Schoen R, Silverman W, Martin J, Rabinovitz M, Weissfeld J, Abu-Elmaagd K, Madariaga J, Slivka A, Martini J (2002). "Detecting cholangiocarcinoma in patients with primary sclerosing cholangitis". Gastrointest Endosc 56 (1): 40-7. PMID 12085033.
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| * Levy C, Lymp J, Angulo P, Gores G, Larusso N, Lindor K (2005). "The value of serum CA 19-9 in predicting cholangiocarcinomas in patients with primary sclerosing cholangitis". Dig Dis Sci 50 (9): 1734–40. PMID 16133981.
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| * Patel A, Harnois D, Klee G, LaRusso N, Gores G (2000). "The utility of CA 19-9 in the diagnoses of cholangiocarcinoma in patients without primary sclerosing cholangitis". Am J Gastroenterol 95 (1): 204-7. PMID 10638584.
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| 40.Saini S (1997). "Imaging of the hepatobiliary tract". N Engl J Med 336 (26): 1889–94. PMID 9197218.
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| 41.Sharma M, Ahuja V. "Aetiological spectrum of obstructive jaundice and diagnostic ability of ultrasonography: a clinician's perspective". Trop Gastroenterol 20 (4): 167-9. PMID 10769604.
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| 42.Bloom C, Langer B, Wilson S. "Role of US in the detection, characterization, and staging of cholangiocarcinoma". Radiographics 19 (5): 1199-218. PMID 10489176.
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| 43.Valls C, Gumà A, Puig I, Sanchez A, Andía E, Serrano T, Figueras J. "Intrahepatic peripheral cholangiocarcinoma: CT evaluation". Abdom Imaging 25 (5): 490-6. PMID 10931983.
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| 44.Tillich M, Mischinger H, Preisegger K, Rabl H, Szolar D (1998). "Multiphasic helical CT in diagnosis and staging of hilar cholangiocarcinoma". AJR Am J Roentgenol 171 (3): 651-8. PMID 9725291.
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| 45.Zhang Y, Uchida M, Abe T, Nishimura H, Hayabuchi N, Nakashima Y. "Intrahepatic peripheral cholangiocarcinoma: comparison of dynamic CT and dynamic MRI". J Comput Assist Tomogr 23 (5): 670-7. PMID 10524843.
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| 46. Sugiyama M, Hagi H, Atomi Y, Saito M. "Diagnosis of portal venous invasion by pancreatobiliary carcinoma: value of endoscopic ultrasonography". Abdom Imaging 22 (4): 434-8. PMID 9157867.
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| 47.Schwartz L, Coakley F, Sun Y, Blumgart L, Fong Y, Panicek D (1998). "Neoplastic pancreaticobiliary duct obstruction: evaluation with breath-hold MR cholangiopancreatography". AJR Am J Roentgenol 170 (6): 1491–5. PMID 9609160.
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| 48.Zidi S, Prat F, Le Guen O, Rondeau Y, Pelletier G (2000). "Performance characteristics of magnetic resonance cholangiography in the staging of malignant hilar strictures". Gut 46 (1): 103-6. PMID 10601064.
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| 49.Lee M, Park K, Shin Y, Yoon H, Sung K, Kim M, Lee S, Kang E (2003). "Preoperative evaluation of hilar cholangiocarcinoma with contrast-enhanced three-dimensional fast imaging with steady-state precession magnetic resonance angiography: comparison with intraarterial digital subtraction angiography". World J Surg 27 (3): 278-83. PMID 12607051.
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| 50.Yeh T, Jan Y, Tseng J, Chiu C, Chen T, Hwang T, Chen M (2000). "Malignant perihilar biliary obstruction: magnetic resonance cholangiopancreatographic findings". Am J Gastroenterol 95 (2): 432-40. PMID 10685746.
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| 51.Freeman M, Sielaff T (2003). "A modern approach to malignant hilar biliary obstruction". Rev Gastroenterol Disord 3 (4): 187–201. PMID 14668691.
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| 52.Szklaruk J, Tamm E, Charnsangavej C (2002). "Preoperative imaging of biliary tract cancers". Surg Oncol Clin N Am 11 (4): 865-76. PMID 12607576.
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| 53. Weber S, DeMatteo R, Fong Y, Blumgart L, Jarnagin W (2002). "Staging laparoscopy in patients with extrahepatic biliary carcinoma. Analysis of 100 patients". Ann Surg 235 (3): 392-9. PMID 11882761.
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| 54. Callery M, Strasberg S, Doherty G, Soper N, Norton J (1997). "Staging laparoscopy with laparoscopic ultrasonography: optimizing resectability in hepatobiliary and pancreatic malignancy". J Am Coll Surg 185 (1): 33-9. PMID 9208958.
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| 55.Länger F, von Wasielewski R, Kreipe HH (2006). "[The importance of immunohistochemistry for the diagnosis of cholangiocarcinomas]" (in German). Pathologe 27 (4): 244-50. PMID 16758167.
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| 56. Darwin PE, Kennedy A. Cholangiocarcinoma. eMedicine.com. URL: http://www.emedicine.com/med/topic343.htm. Accessed on: May 5, 2007.
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| 57. Zervos E, Osborne D, Goldin S, Villadolid D, Thometz D, Durkin A, Carey L, Rosemurgy A (2005). "Stage does not predict survival after resection of hilar cholangiocarcinomas promoting an aggressive operative approach". Am J Surg 190 (5): 810-5. PMID 16226963.
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| 58.Tsao J, Nimura Y, Kamiya J, Hayakawa N, Kondo S, Nagino M, Miyachi M, Kanai M, Uesaka K, Oda K, Rossi R, Braasch J, Dugan J (2000). "Management of hilar cholangiocarcinoma: comparison of an American and a Japanese experience". Ann Surg 232 (2): 166-74. PMID 10903592.
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| 59. Rajagopalan V, Daines W, Grossbard M, Kozuch P (2004). "Gallbladder and biliary tract carcinoma: A comprehensive update, Part 1". Oncology (Williston Park) 18 (7): 889-96. PMID 15255172.
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| 60.Studies of surgical outcomes in distal cholangiocarcinoma include:
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| * Nakeeb A, Pitt H, Sohn T, Coleman J, Abrams R, Piantadosi S, Hruban R, Lillemoe K, Yeo C, Cameron J (1996). "Cholangiocarcinoma. A spectrum of intrahepatic, perihilar, and distal tumors". Ann Surg 224 (4): 463–73; discussion 473-5. PMID 8857851.
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| * Nagorney D, Donohue J, Farnell M, Schleck C, Ilstrup D (1993). "Outcomes after curative resections of cholangiocarcinoma". Arch Surg 128 (8): 871–7; discussion 877-9. PMID 8393652.
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| * Jang J, Kim S, Park D, Ahn Y, Yoon Y, Choi M, Suh K, Lee K, Park Y (2005). "Actual long-term outcome of extrahepatic bile duct cancer after surgical resection". Ann Surg 241 (1): 77–84. PMID 15621994.
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| * Bortolasi L, Burgart L, Tsiotos G, Luque-De León E, Sarr M (2000). "Adenocarcinoma of the distal bile duct. A clinicopathologic outcome analysis after curative resection". Dig Surg 17 (1): 36–41. PMID 10720830.
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| * Fong Y, Blumgart L, Lin E, Fortner J, Brennan M (1996). "Outcome of treatment for distal bile duct cancer". Br J Surg 83 (12): 1712–5. PMID 9038548.
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| 61.Studies of outcome in intrahepatic cholangiocarcinoma include:
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| * Nakeeb A, Pitt H, Sohn T, Coleman J, Abrams R, Piantadosi S, Hruban R, Lillemoe K, Yeo C, Cameron J (1996). "Cholangiocarcinoma. A spectrum of intrahepatic, perihilar, and distal tumors". Ann Surg 224 (4): 463–73; discussion 473-5. PMID 8857851.
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| * Lieser M, Barry M, Rowland C, Ilstrup D, Nagorney D (1998). "Surgical management of intrahepatic cholangiocarcinoma: a 31-year experience". J Hepatobiliary Pancreat Surg 5 (1): 41-7. PMID 9683753.
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| * Valverde A, Bonhomme N, Farges O, Sauvanet A, Flejou J, Belghiti J (1999). "Resection of intrahepatic cholangiocarcinoma: a Western experience". J Hepatobiliary Pancreat Surg 6 (2): 122-7. PMID 10398898.
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| * Nakagohri T, Asano T, Kinoshita H, Kenmochi T, Urashima T, Miura F, Ochiai T (2003). "Aggressive surgical resection for hilar-invasive and peripheral intrahepatic cholangiocarcinoma". World J Surg 27 (3): 289-93. PMID 12607053.
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| * Weber S, Jarnagin W, Klimstra D, DeMatteo R, Fong Y, Blumgart L (2001). "Intrahepatic cholangiocarcinoma: resectability, recurrence pattern, and outcomes". J Am Coll Surg 193 (4): 384-91. PMID 11584966.
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| 62.Estimates of survival after surgery for perihilar cholangiocarcinoma include:
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| * Burke E, Jarnagin W, Hochwald S, Pisters P, Fong Y, Blumgart L (1998). "Hilar Cholangiocarcinoma: patterns of spread, the importance of hepatic resection for curative operation, and a presurgical clinical staging system". Ann Surg 228 (3): 385-94. PMID 9742921.
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| * Tsao J, Nimura Y, Kamiya J, Hayakawa N, Kondo S, Nagino M, Miyachi M, Kanai M, Uesaka K, Oda K, Rossi R, Braasch J, Dugan J (2000). "Management of hilar cholangiocarcinoma: comparison of an American and a Japanese experience". Ann Surg 232 (2): 166-74. PMID 10903592.
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| * Chamberlain R, Blumgart L. "Hilar cholangiocarcinoma: a review and commentary". Ann Surg Oncol 7 (1): 55–66. PMID 10674450.
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| * Washburn W, Lewis W, Jenkins R (1995). "Aggressive surgical resection for cholangiocarcinoma". Arch Surg 130 (3): 270-6. PMID 7534059.
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| * Nagino M, Nimura Y, Kamiya J, Kanai M, Uesaka K, Hayakawa N, Yamamoto H, Kondo S, Nishio H. "Segmental liver resections for hilar cholangiocarcinoma". Hepatogastroenterology 45 (19): 7–13. PMID 9496478.
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| * Rea D, Munoz-Juarez M, Farnell M, Donohue J, Que F, Crownhart B, Larson D, Nagorney D (2004). "Major hepatic resection for hilar cholangiocarcinoma: analysis of 46 patients". Arch Surg 139 (5): 514–23; discussion 523-5. PMID 15136352.
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| * Launois B, Reding R, Lebeau G, Buard J (2000). "Surgery for hilar cholangiocarcinoma: French experience in a collective survey of 552 extrahepatic bile duct cancers". J Hepatobiliary Pancreat Surg 7 (2): 128-34. PMID 10982604.
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| 63. Kaya M, de Groen P, Angulo P, Nagorney D, Gunderson L, Gores G, Haddock M, Lindor K (2001). "Treatment of cholangiocarcinoma complicating primary sclerosing cholangitis: the Mayo Clinic experience". Am J Gastroenterol 96 (4): 1164–9. PMID 11316165.
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| 64. Nakeeb A, Tran K, Black M, Erickson B, Ritch P, Quebbeman E, Wilson S, Demeure M, Rilling W, Dua K, Pitt H (2002). "Improved survival in resected biliary malignancies". Surgery 132 (4): 555–63; discission 563-4. PMID 12407338.
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| 65. Farley D, Weaver A, Nagorney D (1995). ""Natural history" of unresected cholangiocarcinoma: patient outcome after noncurative intervention". Mayo Clin Proc 70 (5): 425-9. PMID 7537346.
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| 66. Su C, Tsay S, Wu C, Shyr Y, King K, Lee C, Lui W, Liu T, P'eng F (1996). "Factors influencing postoperative morbidity, mortality, and survival after resection for hilar cholangiocarcinoma". Ann Surg 223 (4): 384-94. PMID 8633917.
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| 67. Heimbach JK, Gores GJ, Haddock MG, et al, Predictors of disease recurrence following neoadjuvant chemoradiotherapy and liver transplantation for unresectable perihilar cholangiocarcinoma, Transplantation. 2006 Dec 27;82(12):1703-7.
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| 68. Todoroki T, Ohara K, Kawamoto T, Koike N, Yoshida S, Kashiwagi H, Otsuka M, Fukao K (2000). "Benefits of adjuvant radiotherapy after radical resection of locally advanced main hepatic duct carcinoma". Int J Radiat Oncol Biol Phys 46 (3): 581-7. PMID 10701737.
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| 69. Alden M, Mohiuddin M (1994). "The impact of radiation dose in combined external beam and intraluminal Ir-192 brachytherapy for bile duct cancer". Int J Radiat Oncol Biol Phys 28 (4): 945-51. PMID 8138448.
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| 71.Pitt H, Nakeeb A, Abrams R, Coleman J, Piantadosi S, Yeo C, Lillemore K, Cameron J (1995). "Perihilar cholangiocarcinoma. Postoperative radiotherapy does not improve survival". Ann Surg 221 (6): 788–97; discussion 797-8. PMID 7794082.
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| 72.Takada T, Amano H, Yasuda H, Nimura Y, Matsushiro T, Kato H, Nagakawa T, Nakayama T (2002). "Is postoperative adjuvant chemotherapy useful for gallbladder carcinoma? A phase III multicenter prospective randomized controlled trial in patients with resected pancreaticobiliary carcinoma". Cancer 95 (8): 1685–95. PMID 12365016.
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| 73.National Comprehensive Cancer Network (NCCN) guidelines on evaluation and treatment of hepatobiliary malignanciesPDF (216 KiB). Accessed March 13, 2007.
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| 74. Vauthey J, Blumgart L (1994). "Recent advances in the management of cholangiocarcinomas". Semin. Liver Dis. 14 (2): 109-14. PMID 8047893.
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| 75.Glimelius B, Hoffman K, Sjödén P, Jacobsson G, Sellström H, Enander L, Linné T, Svensson C (1996). "Chemotherapy improves survival and quality of life in advanced pancreatic and biliary cancer". Ann Oncol 7 (6): 593–600. PMID 8879373.
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| 76.Choi C, Choi I, Seo J, Kim B, Kim J, Kim C, Um S, Kim J, Kim Y (2000). "Effects of 5-fluorouracil and leucovorin in the treatment of pancreatic-biliary tract adenocarcinomas". Am J Clin Oncol 23 (4): 425-8. PMID 10955877.
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