Cholangiocarcinoma: Difference between revisions

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*{{cite journal |author=Bortolasi L, Burgart L, Tsiotos G, Luque-De León E, Sarr M |title=Adenocarcinoma of the distal bile duct. A clinicopathologic outcome analysis after curative resection |journal=Dig Surg |volume=17 |issue=1 |pages=36-41 |year=2000 |pmid=10720830}}
*{{cite journal |author=Bortolasi L, Burgart L, Tsiotos G, Luque-De León E, Sarr M |title=Adenocarcinoma of the distal bile duct. A clinicopathologic outcome analysis after curative resection |journal=Dig Surg |volume=17 |issue=1 |pages=36-41 |year=2000 |pmid=10720830}}
*{{cite journal |author=Fong Y, Blumgart L, Lin E, Fortner J, Brennan M |title=Outcome of treatment for distal bile duct cancer |journal=Br J Surg |volume=83 |issue=12 |pages=1712-5 |year=1996 |pmid=9038548}}</ref>
*{{cite journal |author=Fong Y, Blumgart L, Lin E, Fortner J, Brennan M |title=Outcome of treatment for distal bile duct cancer |journal=Br J Surg |volume=83 |issue=12 |pages=1712-5 |year=1996 |pmid=9038548}}</ref>

Intrahepatic cholangiocarcinomas (those arising from the bile ducts within the [[liver]]) are usually treated with [[hepatectomy|partial hepatectomy]]. Various series have reported survival estimates after surgery ranging from 22%&ndash;66%; the outcome may depend on involvement of lymph nodes and completeness of the surgery.<ref>Studies of outcome in intrahepatic cholangiocarcinoma include:
*{{cite journal |author=Nakeeb A, Pitt H, Sohn T, Coleman J, Abrams R, Piantadosi S, Hruban R, Lillemoe K, Yeo C, Cameron J |title=Cholangiocarcinoma. A spectrum of intrahepatic, perihilar, and distal tumors |journal=Ann Surg |volume=224 |issue=4 |pages=463-73; discussion 473-5 |year=1996 |pmid=8857851}}
*{{cite journal |author=Lieser M, Barry M, Rowland C, Ilstrup D, Nagorney D |title=Surgical management of intrahepatic cholangiocarcinoma: a 31-year experience |journal=J Hepatobiliary Pancreat Surg |volume=5 |issue=1 |pages=41-7 |year=1998 |pmid=9683753}}
*{{cite journal |author=Valverde A, Bonhomme N, Farges O, Sauvanet A, Flejou J, Belghiti J |title=Resection of intrahepatic cholangiocarcinoma: a Western experience |journal=J Hepatobiliary Pancreat Surg |volume=6 |issue=2 |pages=122-7 |year=1999 |pmid=10398898}}
*{{cite journal |author=Nakagohri T, Asano T, Kinoshita H, Kenmochi T, Urashima T, Miura F, Ochiai T |title=Aggressive surgical resection for hilar-invasive and peripheral intrahepatic cholangiocarcinoma |journal=World J Surg |volume=27 |issue=3 |pages=289-93 |year=2003 |pmid=12607053}}
*{{cite journal |author=Weber S, Jarnagin W, Klimstra D, DeMatteo R, Fong Y, Blumgart L |title=Intrahepatic cholangiocarcinoma: resectability, recurrence pattern, and outcomes |journal=J Am Coll Surg |volume=193 |issue=4 |pages=384-91 |year=2001 |pmid=11584966}}</ref>


The [[prognosis]] may be even worse for patients with primary sclerosing cholangitis who develop cholangiocarcinoma, likely because the cancer is not detected until it is advanced.<ref name="autopsy"/><ref>{{cite journal |author=Kaya M, de Groen P, Angulo P, Nagorney D, Gunderson L, Gores G, Haddock M, Lindor K |title=Treatment of cholangiocarcinoma complicating primary sclerosing cholangitis: the Mayo Clinic experience |journal=Am J Gastroenterol |volume=96 |issue=4 |pages=1164-9 |year=2001 |pmid=11316165}}</ref> Some evidence suggests that outcomes may be improving with more aggressive surgical approaches and [[adjuvant#oncology|adjuvant therapy]].<ref>{{cite journal |author=Nakeeb A, Tran K, Black M, Erickson B, Ritch P, Quebbeman E, Wilson S, Demeure M, Rilling W, Dua K, Pitt H |title=Improved survival in resected biliary malignancies |journal=Surgery |volume=132 |issue=4 |pages=555-63; discission 563-4 |year=2002 |pmid=12407338}}</ref>
The [[prognosis]] may be even worse for patients with primary sclerosing cholangitis who develop cholangiocarcinoma, likely because the cancer is not detected until it is advanced.<ref name="autopsy"/><ref>{{cite journal |author=Kaya M, de Groen P, Angulo P, Nagorney D, Gunderson L, Gores G, Haddock M, Lindor K |title=Treatment of cholangiocarcinoma complicating primary sclerosing cholangitis: the Mayo Clinic experience |journal=Am J Gastroenterol |volume=96 |issue=4 |pages=1164-9 |year=2001 |pmid=11316165}}</ref> Some evidence suggests that outcomes may be improving with more aggressive surgical approaches and [[adjuvant#oncology|adjuvant therapy]].<ref>{{cite journal |author=Nakeeb A, Tran K, Black M, Erickson B, Ritch P, Quebbeman E, Wilson S, Demeure M, Rilling W, Dua K, Pitt H |title=Improved survival in resected biliary malignancies |journal=Surgery |volume=132 |issue=4 |pages=555-63; discission 563-4 |year=2002 |pmid=12407338}}</ref>

Revision as of 00:02, 23 March 2007

Cholangiocarcinoma
SpecialtyOncology Edit this on Wikidata

Cholangiocarcinoma is cancer of the bile ducts. It is a relatively rare cancer, with an annual incidence of 1–2 cases per 100,000 in the Western world,[1] but rates of cholangiocarcinoma have been rising worldwide over the past several decades.[2] Cholangiocarcinoma can affect any area of the bile ducts, either within or outside the liver. A cholangiocarcinoma occurring at the junction of the left and right hepatic bile ducts may be referred to eponymously as a Klatskin tumor.[3]

Risk factors for cholangiocarcinoma include primary sclerosing cholangitis (an inflammatory disease of the bile ducts), congenital liver malformations, infection with the liver flukes Opisthorchis viverrini or Clonorchis sinensis, and exposure to Thorotrast (thorium dioxide). The symptoms of cholangiocarcinoma include jaundice, weight loss, and sometimes generalized itching. The disease is diagnosed through a combination of blood tests, imaging, endoscopy, and sometimes surgical exploration.

Surgery is the only potentially curative treatment, but most patients have advanced and inoperable disease at the time of diagnosis. After surgery, adjuvant chemotherapy or radiation therapy may be given. 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 therapies (such as erlotinib) and the use of photodynamic therapy.

Symptoms

File:PHIL 2860 lores.jpg
Yellowing of the skin and eyes (jaundice)

The most common symptom of cholangiocarcinoma is jaundice, which occurs when bile ducts are blocked by the tumor. Other common symptoms include (in order of frequency) generalized itching (66%), abdominal pain (30%–50%), weight loss (30%–50%), and fever (up to 20%).[4] To some extent, the symptoms depend upon the location of the tumor; patients with cholangiocarcinoma in the extrahepatic bile ducts (outside the liver) are more likely to have jaundice, while those with intrahepatic tumors often have pain without jaundice.[5]

Blood tests of liver function in patients with cholangiocarcinoma often reveal a so-called "obstructive picture", with elevated bilirubin, alkaline phosphatase, and gamma glutamyl transferase levels and relatively normal transaminase levels. Such laboratory findings suggest obstruction of the bile ducts, rather than inflammation or infection of the liver, as the primary cause of the jaundice.[6]

Epidemiology

Cholangiocarcinoma is a relatively rare form of cancer; each year, approximately 2,000 to 3,000 new cases are diagnosed in the United States, translating into an annual incidence of 1–2 cases per 100,000 people.[1] Autopsy series have reported a prevalence of 0.01% to 0.46%.[7] There is a higher prevalence of cholangiocarcinoma among Asian people that is attributed to endemic chronic parasitic infestation. The incidence of cholangiocarcinoma increases with age, and the disease is slightly more common in men than in women (possibly due to the higher rate of primary sclerosing cholangitis, a major risk factor, in men).[8] The prevalence of cholangiocarcinoma in patients with primary sclerosing cholangitis may be as high as 30%, based on autopsy studies.[9]

Multiple studies have documented a steady increase in the incidence of intrahepatic cholangiocarcinoma over the past several decades; increases have been seen in North America, Europe, Asia, and Australia.[10] The reasons for the increasing occurrence of cholangiocarcinoma are unclear; improved diagnostic methods may be partially responsible, but the prevalence of risk factors for cholangiocarcinoma, such as HIV infection, has also been increasing during this time frame.[11]

Risk factors

Life cycle of Clonorchis sinensis, a liver fluke associated with cholangiocarcinoma

A number of risk factors for the development of cholangiocarcinoma have been described; in the Western world, the most common of these is primary sclerosing cholangitis (PSC), an inflammatory disease of the bile ducts which is in turn closely associated with ulcerative colitis (UC).[12] Epidemiologic studies have suggested that the lifetime risk of developing cholangiocarcinoma for a person with PSC is 10%–15%,[13] although autopsy series have found rates as high as 30% in this population.[9] The mechanism by which PSC increases the risk of cholangiocarcinoma is not well-understood.

Congenital liver abnormalities, such as Caroli's syndrome or choledochal cysts, have been associated with an approximately 15% lifetime risk of developing cholangiocarcinoma.[14][15] The rare inherited disorders Lynch syndrome II and biliary papillomatosis are associated with cholangiocarcinoma.[16][17]

Certain parasitic liver diseases may be risk factors as well. Colonization with the liver flukes Opisthorchis viverrini (found in Thailand, Laos, and Malaysia) or Clonorchis sinensis (found in Japan, Korea, and Vietnam) has been associated with the development of cholangiocarcinoma.[18][19][20] Patients with chronic liver disease, whether in the form of viral hepatitis (e.g. hepatitis B or C),[21][22][23] alcoholic liver disease, or cirrhosis from other causes, are at increased risk of cholangiocarcinoma.[11][24] HIV infection was also identified in one study as a risk factor for cholangiocarcinoma, although it was unclear whether HIV itself or correlated factors (e.g. hepatitis C infection) were responsible for the association.[11]

The presence of gallstones (cholelithiasis) is not clearly associated with cholangiocarcinoma. However, intrahepatic stones (so-called hepatolithiasis), which are rare in the West but common in parts of Asia, have been strongly associated with cholangiocarcinoma.[25][26][27]

Exposure to Thorotrast, a form of thorium dioxide which was used as a radiologic contrast medium, has been linked to the development of cholangiocarcinoma as late as 30-40 years after exposure; Thorotrast was banned in the United States in the 1950s due to its carcinogenicity.[28][29]

Pathophysiology

The cell of origin of cholangiocarcinoma is unknown, although recent evidence has suggested that it may arise from a pluripotent hepatic stem cell.[30][31][32] Cholangiocarcinoma is thought to develop through a series of stages — from early hyperplasia and metaplasia, through dysplasia, to the development of frank carcinoma — in a process similar to that seen in the development of colon cancer.[33] Chronic inflammation and obstruction of the bile ducts, and the resulting impaired bile flow, are thought to play a role in this progression.[33][34][35]

Histologically, cholangiocarcinomas may vary from undifferentiated to well-differentiated. They are often surrounded by a brisk fibrotic or desmoplastic tissue response; in the presence of extensive fibrosis, it can be difficult to distinguish well-differentiated cholangiocarcinoma from normal reactive epithelium. There is no entirely specific immunohistochemical stain that can distinguish malignant from benign biliary ductal tissue, although staining for cytokeratins, carcinoembryonic antigen, and mucins may aid in diagnosis.[36] Most tumors (>90%) are adenocarcinomas.[37]

Diagnosis

Cholangiocarcinoma may be suspected in a patient with obstructive jaundice. However, the diagnosis may be especially 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.

Blood tests

There are no specific blood tests that can diagnose cholangiocarcinoma. Serum levels of carcinoembryonic antigen (CEA) and CA19-9 are often elevated, but are not sensitive or specific enough to be used as a general screening tool. However, they may be useful in conjunction with imaging methods in supporting a suspected diagnosis of cholangiocarcinoma.[38]

Abdominal imaging

Ultrasound of the liver and biliary tree is often used as the initial imaging modality in patients with suspected obstructive jaundice.[39][40] Ultrasound can identify obstruction and ductal dilatation and, in some cases, may be sufficient to diagnose cholangiocarcinoma.[41] Computed tomography (CT) scanning may also play an important role in the diagnosis of cholangiocarcinoma.[42][43][44]

Imaging of the biliary tree

While abdominal imaging can be useful in the diagnosis of cholangiocarcinoma, direct imaging of the bile ducts is often necessary. Endoscopic retrograde cholangiopancreatography (ERCP), an endoscopic procedure performed by a gastroenterologist, has been widely used for this purpose. Although ERCP is an invasive procedure with attendant risks, its advantages include the ability to obtain biopsies and to place stents or perform other interventions to relieve biliary obstruction.[6] Endoscopic ultrasound can also be performed at the time of ERCP and may increase the accuracy of the biopsy and yield information on lymph node invasion and operability.[45] As an alternative to ERCP, percutaneous transhepatic cholangiography (PTC) may be utilized.

Magnetic resonance cholangiopancreatography (MRCP) is a non-invasive alternative to ERCP.[46][47][48] Some authors have suggested that MRCP should supplant ERCP in the diagnosis of biliary cancers, as it may more accurately define the tumor and avoids the risks of ERCP.[49][50][51]

Surgery

Surgical exploration may be necessary to obtain a suitable biopsy and to accurately stage patient with cholangiocarcinoma. Laparoscopy can be used for staging purposes and may avoid the need for a more invasive surgical procedure, such as laparotomy, in some patients.[52][53] Surgery is also the only curative option for cholangiocarcinoma, although it is limited to patients with early-stage disease (see below).

Staging

Although the American Joint Committee on Cancer has published a staging system for cholangiocarcinoma, this system has not been useful in predicting survival.[54] The most important staging issue is whether the tumor can be surgically removed, or whether it is too advanced or invasive for surgical treatment. Often, this determination can only be made at the time of surgery.[6]

General guidelines for operability include:[55][56]

  • Absence of lymph node or liver metastases
  • Absence of involvement of the portal vein
  • Absence of direct invasion of adjacent organs
  • Absence of widespread metastatic disease

Prognosis

Surgical resection offers the only potential chance of cure in cholangiocarcinoma. The odds of cure vary depending on the tumor location and whether the tumor can be completely, or only partially, removed.

Distal cholangiocarcinomas (those arising from the common bile duct) are generally treated with a Whipple procedure; long-term survival rates range from 15%–25%, although one series reported a survival of 54% for patients with no involvement of the lymph nodes.[57]

Intrahepatic cholangiocarcinomas (those arising from the bile ducts within the liver) are usually treated with partial hepatectomy. Various series have reported survival estimates after surgery ranging from 22%–66%; the outcome may depend on involvement of lymph nodes and completeness of the surgery.[58]

The prognosis may be even worse for patients with primary sclerosing cholangitis who develop cholangiocarcinoma, likely because the cancer is not detected until it is advanced.[9][59] Some evidence suggests that outcomes may be improving with more aggressive surgical approaches and adjuvant therapy.[60]

Treatment

Cholangiocarcinoma is considered curable only by surgical resection. Often, the operability of the tumor can only be assessed at the time of surgery;[61] therefore, most patients undergo exploratory surgery unless there is a clear-cut indication that the tumor is inoperable.[6]

Adjuvant chemotherapy and radiation therapy

If the tumor can be removed surgically, patients may receive adjuvant chemotherapy or radiation therapy after the operation to improve the chances of cure. If the tissue margins are negative (i.e. the tumor has been totally excised), adjuvant therapy is of uncertain benefit. Both positive[62][63] and negative[5][64][65] results have been reported with adjuvant radiation therapy in this setting, and no prospective randomized controlled trials have been conducted as of March 2007. Adjuvant chemotherapy appears to be ineffective in patients with completely resected tumors.[66] The role of combined chemoradiotherapy in this setting is unclear.

If the tumor tissue margins are positive, indicating that the tumor was not completely removed via surgery, then adjuvant therapy with radiation and possibly chemotherapy is generally recommended based on the available data.[67]

Treatment of advanced disease

If the tumor cannot be surgically removed, patients are often treated with palliative chemotherapy. Chemotherapy has been shown in a randomized controlled trial to improve quality of life and extend survival in patients with inoperable cholangiocarcinoma.[68]

There is no single chemotherapy regimen which is universally used, and enrollment in clinical trials is often recommended when possible.[67] Chemotherapy agents used to treat cholangiocarcinoma include 5-fluorouracil with leucovorin,[69] gemcitabine as a single agent,[70] or gemcitabine plus cisplatin,[71] irinotecan,[72] or capecitabine.[73] A small pilot study suggested possible benefit from the tyrosine kinase inhibitor erlotinib in patients with advanced cholangiocarcinoma.[74]

Photodynamic therapy, an experimental approach in which patients are injected with a light-sensitizing agent and light is then applied endoscopically directly to the tumor, has shown promising results compared to supportive care in two small randomized controlled trials, although its ultimate role in the management of cholangiocarcinoma is unclear at present.[75][76]

Notes

  1. ^ a b Landis S, Murray T, Bolden S, Wingo P. "Cancer statistics, 1998". CA Cancer J Clin. 48 (1): 6–29. PMID 9449931.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  2. ^ Patel T. "Worldwide trends in mortality from biliary tract malignancies". BMC Cancer. 2: 10. PMID 11991810.
  3. ^ 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.
  4. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  5. ^ a b 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  6. ^ a b c d Feldman, pp. 1493-1496.
  7. ^ Vauthey J, Blumgart L (1994). "Recent advances in the management of cholangiocarcinomas". Semin Liver Dis. 14 (2): 109–14. PMID 8047893.
  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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  9. ^ a b c Rosen C, Nagorney D, Wiesner R, Coffey R, LaRusso N (1991). "Cholangiocarcinoma complicating primary sclerosing cholangitis". Ann Surg. 213 (1): 21–5. PMID 1845927.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  10. ^ Multiple independent studies have documented a steady increase in the worldwide incidence of cholangiocarcinoma. Some relevant journal articles include:
    • Patel T. "Worldwide trends in mortality from biliary tract malignancies". BMC Cancer. 2: 10. PMID 11991810.
    • Patel T (2001). "Increasing incidence and mortality of primary intrahepatic cholangiocarcinoma in the United States". Hepatology. 33 (6): 1353–7. PMID 11391522.
    • 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
    • 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
    • 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
    • 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  11. ^ a b c 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  12. ^ Chapman R. "Risk factors for biliary tract carcinogenesis". Ann Oncol. 10 Suppl 4: 308–11. PMID 10436847.
  13. ^ Epidemiologic studies which have addressed the incidence of cholangiocarcinoma in people with primary sclerosing cholangitis include the following:
    • 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
    • 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
    • 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  14. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  15. ^ Dayton M, Longmire W, Tompkins R (1983). "Caroli's Disease: a premalignant condition?". Am J Surg. 145 (1): 41–8. PMID 6295196.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  16. ^ Mecklin J, Järvinen H, Virolainen M (1992). "The association between cholangiocarcinoma and hereditary nonpolyposis colorectal carcinoma". Cancer. 69 (5): 1112–4. PMID 1310886.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  17. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  18. ^ Watanapa P (1996). "Cholangiocarcinoma in patients with opisthorchiasis". Br J Surg. 83 (8): 1062–64. PMID 8869303.
  19. ^ Watanapa P, Watanapa W (2002). "Liver fluke-associated cholangiocarcinoma". Br J Surg. 89 (8): 962–70. PMID 12153620.
  20. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  21. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  22. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  23. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  24. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  26. ^ Su C, Shyr Y, Lui W, P'Eng F (1997). "Hepatolithiasis associated with cholangiocarcinoma". Br J Surg. 84 (7): 969–73. PMID 9240138.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  29. ^ Zhu A, Lauwers G, Tanabe K (2004). "Cholangiocarcinoma in association with Thorotrast exposure". J Hepatobiliary Pancreat Surg. 11 (6): 430–3. PMID 15619021.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  30. ^ Roskams T (2006). "Liver stem cells and their implication in hepatocellular and cholangiocarcinoma". Oncogene. 25 (27): 3818–22. PMID 16799623.
  31. ^ Liu C, Wang J, Ou Q (2004). "Possible stem cell origin of human cholangiocarcinoma". World J Gastroenterol. 10 (22): 3374–6. PMID 15484322.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  32. ^ 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.
  33. ^ a b Sirica A (2005). "Cholangiocarcinoma: molecular targeting strategies for chemoprevention and therapy". Hepatology. 41 (1): 5–15. PMID 15690474.
  34. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  35. ^ Gores G (2003). "Cholangiocarcinoma: current concepts and insights". Hepatology. 37 (5): 961–9. PMID 12717374.
  36. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  37. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  38. ^ Studies of the performace of serum markers for cholangiocarcinoma (such as carcinoembryonic antigen and CA19-9) in patients with and without primary sclerosing cholangitis include the following:
    • Nehls O, Gregor M, Klump B (2004). "Serum and bile markers for cholangiocarcinoma". Semin Liver Dis. 24 (2): 139–54. PMID 15192787.{{cite journal}}: CS1 maint: multiple names: authors list (link)
    • 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
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  57. ^ Studies of surgical outcomes in distal cholangiocarcinoma include:
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References

  • Feldman: Sleisenger & Fordtran's Gastrointestinal and Liver Disease. 8th ed., copyright © 2006 Saunders, An Imprint of Elsevier.

External links

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