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'''For patient information click [[{{PAGENAME}} (patient information)|here]]'''
'''For patient information click [[{{PAGENAME}} (patient information)|here]]'''
__NOTOC__
{{Cholangiocarcinoma}}
{{CMG}}; {{AE}}{{PSK}}


{{CMG}}
{{SK}} Bile duct cancer; Bile duct carcinoma; Cancer of bile duct; Intrahepatic cholangiocarcinoma; Extrahepatic cholangiocarcinoma; Perihilar cholangiocarcinoma; Hilar cholangiocarcinoma


{{Editor Help}}
==[[Cholangiocarcinoma overview|Overview]]==


==Overview==
==[[Cholangiocarcinoma historical perspective|Historical Perspective]]==
{{Infobox_Disease
| Name          = Cholangiocarcinoma
| Image          = Digestive system showing bile duct.png
| Caption        = Digestive system diagram showing bile duct location
| DiseasesDB    = 2505
| ICD10          = {{ICD10|C|22|1|c|15}}
| ICD9          = {{ICD9|155.1}}, {{ICD9|156.1}}
| ICDO          = 8160/3
| OMIM          =
| MedlinePlus    = 000291
| eMedicineSubj  = med
| eMedicineTopic = 343
| eMedicine_mult = {{eMedicine2|radio|153}}
| MeshID        = D018281
}}
{{SI}}
'''Cholangiocarcinoma''' is a [[cancer]] of the [[bile duct]]s, which drain [[bile]] from the [[liver]] into the [[small intestine]].  It is a relatively rare cancer, with an annual [[incidence (epidemiology)|incidence]] of 1&ndash;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> 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]]. 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.


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]].
==[[Cholangiocarcinoma classification|Classification]]==


==Symptoms==
==[[Cholangiocarcinoma pathophysiology|Pathophysiology]]==
[[Image:PHIL 2860 lores.jpg|thumb|left|Yellowing of the skin and eyes (jaundice)]]
The most common symptom of cholangiocarcinoma is [[jaundice]] (yellowing of the eyes and skin), which occurs when bile ducts are blocked by the tumor. Other common symptoms include, in order of frequency: [[pruritis|generalized itching]] (66%), [[abdominal pain]] (30%&ndash;50%), [[weight loss]] (30%&ndash;50%), and [[fever]] (up to 20%).<ref>{{cite journal |author=Nagorney D, Donohue J, Farnell M, Schleck C, Ilstrup D |title=Outcomes after curative resections of cholangiocarcinoma |journal=Arch Surg |volume=128 |issue=8 |pages=871–7; discussion 877-9 |year=1993 |id=PMID 8393652}}</ref> 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 tumors of the bile ducts within the liver often have pain without jaundice.<ref name="nakeeb">{{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 |id=PMID 8857851}}</ref>


[[Liver function tests|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.<ref name="feldman">Feldman, pp. 1493–1496.</ref>
==[[Cholangiocarcinoma causes|Causes]]==


==Epidemiology==
==[[Cholangiocarcinoma differential diagnosis|Differentiating Cholangiocarcinoma from other Diseases]]==


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 (epidemiology)|incidence]] of 1&ndash;2 cases per 100,000 people.<ref name="Landis"/> [[Autopsy]] series have reported a [[prevalence]] of 0.01% to 0.46%.<ref>{{cite journal |author=Vauthey J, Blumgart L |title=Recent advances in the management of cholangiocarcinomas |journal=Semin Liver Dis |volume=14 |issue=2 |pages=109-14 |year=1994 |id=PMID 8047893}}</ref> There is a higher prevalence of cholangiocarcinoma in Asia, which has been 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).<ref>{{cite journal |author=Henson D, Albores-Saavedra J, Corle D |title=Carcinoma of the extrahepatic bile ducts. Histologic types, stage of disease, grade, and survival rates |journal=Cancer |volume=70 |issue=6 |pages=1498-501 |year=1992 |id=PMID 1516001}}</ref> The prevalence of cholangiocarcinoma in patients with primary sclerosing cholangitis may be as high as 30%, based on autopsy studies.<ref name="autopsy">{{cite journal |author=Rosen C, Nagorney D, Wiesner R, Coffey R, LaRusso N |title=Cholangiocarcinoma complicating primary sclerosing cholangitis |journal=Ann Surg |volume=213 |issue=1 |pages=21-5 |year=1991 |id=PMID 1845927}}</ref>
==[[Cholangiocarcinoma epidemiology and demographics|Epidemiology and Demographics]]==


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.<ref>Multiple independent studies have documented a steady increase in the worldwide incidence of cholangiocarcinoma. Some relevant journal articles include:
==[[Cholangiocarcinoma risk factors|Risk Factors]]==
*{{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}}
*{{cite journal |author=Patel T |title=Increasing incidence and mortality of primary intrahepatic cholangiocarcinoma in the United States |journal=Hepatology |volume=33 |issue=6 |pages=1353–7 |year=2001 |id=PMID 11391522}}
*{{cite journal |author=Shaib Y, Davila J, McGlynn K, El-Serag H |title=Rising incidence of intrahepatic cholangiocarcinoma in the United States: a true increase? |journal=J Hepatol |volume=40 |issue=3 |pages=472-7 |year=2004 |id=PMID 15123362}}
*{{cite journal |author=West J, Wood H, Logan R, Quinn M, Aithal G |title=Trends in the incidence of primary liver and biliary tract cancers in England and Wales 1971–2001 |journal=Br J Cancer |volume=94 |issue=11 |pages=1751–8 |year=2006 |id=PMID 16736026}}
*{{cite journal |author=Khan S, Taylor-Robinson S, Toledano M, Beck A, Elliott P, Thomas H |title=Changing international trends in mortality rates for liver, biliary and pancreatic tumours |journal=J Hepatol |volume=37 |issue=6 |pages=806-13 |year=2002 |id=PMID 12445422}}
*{{cite journal |author=Welzel T, McGlynn K, Hsing A, O'Brien T, Pfeiffer R |title=Impact of classification of hilar cholangiocarcinomas (Klatskin tumors) on the incidence of intra- and extrahepatic cholangiocarcinoma in the United States |journal=J Natl Cancer Inst |volume=98 |issue=12 |pages=873-5 |year=2006 |id=PMID 16788161}}</ref> The reasons for the increasing occurrence of cholangiocarcinoma are unclear; improved diagnostic methods may be partially responsible, but the prevalence of potential risk factors for cholangiocarcinoma, such as [[HIV|HIV infection]], has also been increasing during this time frame.<ref name="riskfactors">{{cite journal |author=Shaib Y, El-Serag H, Davila J, Morgan R, McGlynn K |title=Risk factors of intrahepatic cholangiocarcinoma in the United States: a case-control study |journal=Gastroenterology |volume=128 |issue=3 |pages=620-6 |year=2005 |id=PMID 15765398}}</ref>


{| style="width: 50%; border-collapse: collapse; margin: 0.2em;" border="2" align="left"
==[[Cholangiocarcinoma screening|Screening]]==
|+ align="bottom" | ''[[Age Standardized Mortality Rates|Age-standardized mortality rates]] from intrahepatic (IC) and extrahepatic (EC) cholangiocarcinoma for men and women, by country. Source: Khan et al, 2002.<ref>{{cite journal |author=Khan S, Taylor-Robinson S, Toledano M, Beck A, Elliott P, Thomas H |title=Changing international trends in mortality rates for liver, biliary and pancreatic tumours |journal=J Hepatol |volume=37 |issue=6 |pages=806-13 |year=2002 |pmid=12445422}}</ref>''
|-
! ''Country''
! ''IC (men/women)''
! ''EC (men/women)''
|-
! U.S.A.
| align="center" | 0.60 / 0.43
| align="center" | 0.70 / 0.87
|-
! Japan
| align="center" | 0.23 / 0.10
| align="center" | 5.87 / 5.20
|-
! Australia
| align="center" | 0.70 / 0.53
| align="center" | 0.90 / 1.23
|-
! England/Wales
| align="center" | 0.83 / 0.63
| align="center" | 0.43 / 0.60
|-
! Scotland
| align="center" | 1.17 / 1.00
| align="center" | 0.60 / 0.73
|-
! France
| align="center" | 0.27 / 0.20
| align="center" | 1.20 / 1.37
|-
! Italy
| align="center" | 0.13 / 0.13
| align="center" | 2.10 / 2.60
|}


<br clear="left"/>
==[[Cholangiocarcinoma natural history, complications and prognosis|Natural History, Complications and Prognosis]]==
 
==Risk factors==
[[Image:Clonorchis sinensis LifeCycle.gif|thumb|left|350px|Life cycle of ''[[Clonorchis sinensis]]'', a [[liver fluke]] associated with cholangiocarcinoma]]
 
A number of [[risk factor]]s 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).<ref>{{cite journal |author=Chapman R |title=Risk factors for biliary tract carcinogenesis |journal=Ann Oncol |volume=10 Suppl 4 |issue= |pages=308-11 |year= |id=PMID 10436847}}</ref> Epidemiologic studies have suggested that the lifetime risk of developing cholangiocarcinoma for a person with PSC is 10%&ndash;15%,<ref>Epidemiologic studies which have addressed the incidence of cholangiocarcinoma in people with primary sclerosing cholangitis include the following:
*{{cite journal |author=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 |title=Hepatic and extrahepatic malignancies in primary sclerosing cholangitis |journal=J Hepatol |volume=36 |issue=3 |pages=321-7 |year=2002 |id=PMID 11867174}}
*{{cite journal |author=Bergquist A, Glaumann H, Persson B, Broomé U |title=Risk factors and clinical presentation of hepatobiliary carcinoma in patients with primary sclerosing cholangitis: a case-control study |journal=Hepatology |volume=27 |issue=2 |pages=311-6 |year=1998 |id=PMID 9462625}}
*{{cite journal |author=Burak K, Angulo P, Pasha T, Egan K, Petz J, Lindor K |title=Incidence and risk factors for cholangiocarcinoma in primary sclerosing cholangitis |journal=Am J Gastroenterol |volume=99 |issue=3 |pages=523-6 |year=2004 |id=PMID 15056096}}</ref> although autopsy series have found rates as high as 30% in this population.<ref name="autopsy"/> The mechanism by which PSC increases the risk of cholangiocarcinoma is not well-understood.
 
Certain [[parasitic disease|parasitic liver diseases]] may be risk factors as well. Colonization with the [[liver fluke]]s ''[[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.<ref>{{cite journal |author=Watanapa P |title=Cholangiocarcinoma in patients with opisthorchiasis |journal=Br J Surg |volume=83 |issue=8 |pages=1062–64 |year=1996 |id=PMID 8869303}}</ref><ref>{{cite journal |author=Watanapa P, Watanapa W |title=Liver fluke-associated cholangiocarcinoma |journal=Br J Surg |volume=89 |issue=8 |pages=962-70 |year=2002 |id=PMID 12153620}}</ref><ref>{{cite journal |author=Shin H, Lee C, Park H, Seol S, Chung J, Choi H, Ahn Y, Shigemastu T |title=Hepatitis B and C virus, Clonorchis sinensis for the risk of liver cancer: a case-control study in Pusan, Korea |journal=Int J Epidemiol |volume=25 |issue=5 |pages=933-40 |year=1996 |id=PMID 8921477}}</ref> Patients with chronic liver disease, whether in the form of viral hepatitis (e.g. [[hepatitis B]] or [[hepatitis C|C]]),<ref>{{cite journal |author=Kobayashi M, Ikeda K, Saitoh S, Suzuki F, Tsubota A, Suzuki Y, Arase Y, Murashima N, Chayama K, Kumada H |title=Incidence of primary cholangiocellular carcinoma of the liver in Japanese patients with hepatitis C virus-related cirrhosis |journal=Cancer |volume=88 |issue=11 |pages=2471–7 |year=2000 |id=PMID 10861422}}</ref><ref>{{cite journal |author=Yamamoto S, Kubo S, Hai S, Uenishi T, Yamamoto T, Shuto T, Takemura S, Tanaka H, Yamazaki O, Hirohashi K, Tanaka T |title=Hepatitis C virus infection as a likely etiology of intrahepatic cholangiocarcinoma |journal=Cancer Sci |volume=95 |issue=7 |pages=592-5 |year=2004 |id=PMID 15245596}}</ref><ref>{{cite journal |author=Lu H, Ye M, Thung S, Dash S, Gerber M |title=Detection of hepatitis C virus RNA sequences in cholangiocarcinomas in Chinese and American patients |journal=Chin Med J (Engl) |volume=113 |issue=12 |pages=1138–41 |year=2000 |id=PMID 11776153}}</ref> [[alcoholic liver disease]], or [[cirrhosis]] from other causes, are at increased risk of cholangiocarcinoma.<ref name="riskfactors"/><ref>{{cite journal |author=Sorensen H, Friis S, Olsen J, Thulstrup A, Mellemkjaer L, Linet M, Trichopoulos D, Vilstrup H, Olsen J |title=Risk of liver and other types of cancer in patients with cirrhosis: a nationwide cohort study in Denmark |journal=Hepatology |volume=28 |issue=4 |pages=921-5 |year=1998 |id=PMID 9755226}}</ref> HIV infection was also identified in one study as a potential risk factor for cholangiocarcinoma, although it was unclear whether [[HIV]] itself or correlated factors (e.g. hepatitis C infection) were responsible for the association.<ref name="riskfactors"/>
 
[[Congenital disorder|Congenital]] liver abnormalities, such as [[Caroli's syndrome]] or choledochal cysts, have been associated with an approximately 15% lifetime risk of developing cholangiocarcinoma.<ref>{{cite journal |author=Lipsett P, Pitt H, Colombani P, Boitnott J, Cameron J |title=Choledochal cyst disease. A changing pattern of presentation |journal=Ann Surg |volume=220 |issue=5 |pages=644-52 |year=1994 |id=PMID 7979612}}</ref><ref>{{cite journal |author=Dayton M, Longmire W, Tompkins R |title=Caroli's Disease: a premalignant condition? |journal=Am J Surg |volume=145 |issue=1 |pages=41-8 |year=1983 |id=PMID 6295196}}</ref> The rare inherited disorders [[Lynch syndrome|Lynch syndrome II]] and biliary papillomatosis are associated with cholangiocarcinoma.<ref>{{cite journal |author=Mecklin J, Järvinen H, Virolainen M |title=The association between cholangiocarcinoma and hereditary nonpolyposis colorectal carcinoma |journal=Cancer |volume=69 |issue=5 |pages=1112–4 |year=1992 |id=PMID 1310886}}</ref><ref>{{cite journal |author=Lee S, Kim M, Lee S, Jang S, Song M, Kim K, Kim H, Seo D, Song D, Yu E, Lee S, Min Y |title=Clinicopathologic review of 58 patients with biliary papillomatosis |journal=Cancer |volume=100 |issue=4 |pages=783-93 |year=2004 |id=PMID 14770435}}</ref> 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.<ref>{{cite journal |author=Lee C, Wu C, Chen G |title=What is the impact of coexistence of hepatolithiasis on cholangiocarcinoma? |journal=J Gastroenterol Hepatol |volume=17 |issue=9 |pages=1015–20 |year=2002 |id=PMID 12167124}}</ref><ref>{{cite journal |author=Su C, Shyr Y, Lui W, P'Eng F |title=Hepatolithiasis associated with cholangiocarcinoma |journal=Br J Surg |volume=84 |issue=7 |pages=969-73 |year=1997 |id=PMID 9240138}}</ref><ref>{{cite journal |author=Donato F, Gelatti U, Tagger A, Favret M, Ribero M, Callea F, Martelli C, Savio A, Trevisi P, Nardi G |title=Intrahepatic cholangiocarcinoma and hepatitis C and B virus infection, alcohol intake, and hepatolithiasis: a case-control study in Italy |journal=Cancer Causes Control |volume=12 |issue=10 |pages=959-64 |year=2001 |id=PMID 11808716}}</ref> Exposure to [[Thorotrast]], a form of [[thorium dioxide]] which was used as a [[radiocontrast|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]].<ref>{{cite journal |author=Sahani D, Prasad S, Tannabe K, Hahn P, Mueller P, Saini S |title=Thorotrast-induced cholangiocarcinoma: case report |journal=Abdom Imaging |volume=28 |issue=1 |pages=72-4 |year= |id=PMID 12483389}}</ref><ref>{{cite journal |author=Zhu A, Lauwers G, Tanabe K |title=Cholangiocarcinoma in association with Thorotrast exposure |journal=J Hepatobiliary Pancreat Surg |volume=11 |issue=6 |pages=430-3 |year=2004 |id=PMID 15619021}}</ref>
 
==Pathophysiology==
 
Cholangiocarcinoma can affect any area of the bile ducts, either within or outside the liver. Tumors occurring in the bile ducts within the liver are referred to as ''intrahepatic''; those occurring in the ducts outside the liver are ''extrahepatic'', and tumors occurring at the site where the bile ducts exit the liver may be referred to as ''perihilar''. A cholangiocarcinoma occurring at the junction where the left and right hepatic ducts meet to form the [[common bile duct]] may be referred to [[eponym]]ously as a [[Klatskin tumor]].<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>
 
The cell of origin of cholangiocarcinoma is unknown, although recent evidence has suggested that it may arise from a [[pluripotent]] hepatic [[adult stem cell|stem cell]].<ref>{{cite journal |author=Roskams T |title=Liver stem cells and their implication in hepatocellular and cholangiocarcinoma |journal=Oncogene |volume=25 |issue=27 |pages=3818–22 |year=2006 |id=PMID 16799623}}</ref><ref>{{cite journal |author=Liu C, Wang J, Ou Q |title=Possible stem cell origin of human cholangiocarcinoma |journal=World J Gastroenterol |volume=10 |issue=22 |pages=3374–6 |year=2004 |id=PMID 15484322}}</ref><ref>{{cite journal |author=Sell S, Dunsford H |title=Evidence for the stem cell origin of hepatocellular carcinoma and cholangiocarcinoma |journal=Am J Pathol |volume=134 |issue=6 |pages=1347–63 |year=1989 |id=PMID 2474256}}</ref> Cholangiocarcinoma is thought to develop through a series of stages &mdash; from early [[hyperplasia]] and [[metaplasia]], through [[dysplasia]], to the development of frank [[carcinoma]] &mdash; in a process similar to that seen in the development of [[colon cancer]].<ref name="targeting">{{cite journal |author=Sirica A |title=Cholangiocarcinoma: molecular targeting strategies for chemoprevention and therapy |journal=Hepatology |volume=41 |issue=1 |pages=5–15 |year=2005 |id=PMID 15690474}}</ref> [[inflammation|Chronic inflammation]] and obstruction of the bile ducts, and the resulting impaired bile flow, are thought to play a role in this progression.<ref name="targeting"/><ref>{{cite journal |author=Holzinger F, Z'graggen K, Büchler M |title=Mechanisms of biliary carcinogenesis: a pathogenetic multi-stage cascade towards cholangiocarcinoma |journal=Ann Oncol |volume=10 Suppl 4 |issue= |pages=122-6 |year= |id=PMID 10436802}}</ref><ref>{{cite journal |author=Gores G |title=Cholangiocarcinoma: current concepts and insights |journal=Hepatology |volume=37 |issue=5 |pages=961-9 |year=2003 |id=PMID 12717374}}</ref>
 
[[Histology|Histologically]], cholangiocarcinomas may vary from [[cellular differentiation|undifferentiated to well-differentiated]]. They are often surrounded by a brisk [[fibrosis|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 [[immunohistochemistry|immunohistochemical]] stain that can distinguish [[malignant]] from [[benign]] biliary ductal tissue, although staining for [[cytokeratin]]s, [[carcinoembryonic antigen]], and [[mucin]]s may aid in diagnosis.<ref name="nejm">{{cite journal |author=de Groen P, Gores G, LaRusso N, Gunderson L, Nagorney D |title=Biliary tract cancers |journal=N Engl J Med |volume=341 |issue=18 |pages=1368–78 |year=1999 |id=PMID 10536130}}</ref> Most tumors (>90%) are [[adenocarcinoma]]s.<ref>{{cite journal |author=Henson D, Albores-Saavedra J, Corle D |title=Carcinoma of the extrahepatic bile ducts. Histologic types, stage of disease, grade, and survival rates |journal=Cancer |volume=70 |issue=6 |pages=1498-501 |year=1992 |id=PMID 1516001}}</ref>


==Diagnosis==
==Diagnosis==
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.
[[Cholangiocarcinoma staging|Staging]] | [[Cholangiocarcinoma history and symptoms|History and Symptoms]] | [[Cholangiocarcinoma physical examination|Physical Examination]] | [[Cholangiocarcinoma laboratory tests|Laboratory Findings]] | [[Cholangiocarcinoma CT|CT]] | [[Cholangiocarcinoma MRI|MRI]] | [[Cholangiocarcinoma echocardiography or ultrasound|Abdominal Ultrasound]] | [[Cholangiocarcinoma other imaging findings|Other Imaging Findings]] | [[Cholangiocarcinoma other diagnostic studies|Other Diagnostic Studies]] |
 
===Blood tests===
There are no specific [[blood test]]s that can diagnose cholangiocarcinoma by themselves. Serum levels of [[carcinoembryonic antigen]] (CEA) and CA19-9 are often elevated, but are not [[sensitivity (tests)|sensitive]] or [[specificity (tests)|specific]] enough to be used as a general [[screening (medicine)|screening]] tool. However, they may be useful in conjunction with [[medical imaging|imaging methods]] in supporting a suspected diagnosis of cholangiocarcinoma.<ref>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:
*{{cite journal |author=Nehls O, Gregor M, Klump B |title=Serum and bile markers for cholangiocarcinoma |journal=Semin Liver Dis |volume=24 |issue=2 |pages=139-54 |year=2004 |id=PMID 15192787}}
*{{cite journal |author=Siqueira E, Schoen R, Silverman W, Martin J, Rabinovitz M, Weissfeld J, Abu-Elmaagd K, Madariaga J, Slivka A, Martini J |title=Detecting cholangiocarcinoma in patients with primary sclerosing cholangitis |journal=Gastrointest Endosc |volume=56 |issue=1 |pages=40-7 |year=2002 |id=PMID 12085033}}
*{{cite journal |author=Levy C, Lymp J, Angulo P, Gores G, Larusso N, Lindor K |title=The value of serum CA 19-9 in predicting cholangiocarcinomas in patients with primary sclerosing cholangitis |journal=Dig Dis Sci |volume=50 |issue=9 |pages=1734–40 |year=2005 |id=PMID 16133981}}
*{{cite journal |author=Patel A, Harnois D, Klee G, LaRusso N, Gores G |title=The utility of CA 19-9 in the diagnoses of cholangiocarcinoma in patients without primary sclerosing cholangitis |journal=Am J Gastroenterol |volume=95 |issue=1 |pages=204-7 |year=2000 |id=PMID 10638584}}</ref>
 
===Abdominal imaging===
[[Image:CT cholangioca.jpg|left|thumb|[[Computed tomography|CT scan]] showing cholangiocarcinoma]]
[[Ultrasound]] of the [[liver]] and [[biliary tree]] is often used as the initial imaging modality in patients with suspected obstructive jaundice.<ref>{{cite journal |author=Saini S |title=Imaging of the hepatobiliary tract |journal=N Engl J Med |volume=336 |issue=26 |pages=1889–94 |year=1997 |id=PMID 9197218}}</ref><ref>{{cite journal |author=Sharma M, Ahuja V |title=Aetiological spectrum of obstructive jaundice and diagnostic ability of ultrasonography: a clinician's perspective |journal=Trop Gastroenterol |volume=20 |issue=4 |pages=167-9 |year= |id=PMID 10769604}}</ref>
 
Ultrasound can identify obstruction and ductal dilatation and, in some cases, may be sufficient to diagnose cholangiocarcinoma.<ref>{{cite journal |author=Bloom C, Langer B, Wilson S |title=Role of US in the detection, characterization, and staging of cholangiocarcinoma |journal=Radiographics |volume=19 |issue=5 |pages=1199-218 |year= |id=PMID 10489176}}</ref>
 
[[Computed tomography]] (CT) scanning may also play an important role in the diagnosis of cholangiocarcinoma.<ref>{{cite journal |author=Valls C, Gumà A, Puig I, Sanchez A, Andía E, Serrano T, Figueras J |title=Intrahepatic peripheral cholangiocarcinoma: CT evaluation |journal=Abdom Imaging |volume=25 |issue=5 |pages=490-6 |year= |id=PMID 10931983}}</ref><ref>{{cite journal |author=Tillich M, Mischinger H, Preisegger K, Rabl H, Szolar D |title=Multiphasic helical CT in diagnosis and staging of hilar cholangiocarcinoma |journal=AJR Am J Roentgenol |volume=171 |issue=3 |pages=651-8 |year=1998 |id=PMID 9725291}}</ref><ref>{{cite journal |author=Zhang Y, Uchida M, Abe T, Nishimura H, Hayabuchi N, Nakashima Y |title=Intrahepatic peripheral cholangiocarcinoma: comparison of dynamic CT and dynamic MRI |journal=J Comput Assist Tomogr |volume=23 |issue=5 |pages=670-7 |year= |id=PMID 10524843}}</ref>
<br clear="left"/>
 
===Imaging of the biliary tree===
[[Image:ERCP cholangioca.jpg|thumb|left|[[ERCP]] image of cholangiocarcinoma, showing common bile duct stricture and dilation of the proximal common bile duct]]
While abdominal imaging can be useful in the diagnosis of cholangiocarcinoma, direct imaging of the [[bile duct]]s is often necessary. [[Endoscopic retrograde cholangiopancreatography]] (ERCP), an [[endoscopy|endoscopic]] procedure performed by a [[gastroenterologist]] or specially trained surgeon, has been widely used for this purpose.
 
Although ERCP is an invasive procedure with attendant risks, its advantages include the ability to obtain [[biopsy|biopsies]] and to place [[stent]]s or perform other interventions to relieve biliary obstruction.<ref name="feldman"/>
 
[[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.<ref>{{cite journal |author=Sugiyama M, Hagi H, Atomi Y, Saito M |title=Diagnosis of portal venous invasion by pancreatobiliary carcinoma: value of endoscopic ultrasonography |journal=Abdom Imaging |volume=22 |issue=4 |pages=434-8 |year= |id=PMID 9157867}}</ref> As an alternative to ERCP, [[percutaneous transhepatic cholangiography]] (PTC) may be utilized.
 
[[Magnetic resonance cholangiopancreatography]] (MRCP) is a [[non-invasive]] alternative to ERCP.<ref>{{cite journal |author=Schwartz L, Coakley F, Sun Y, Blumgart L, Fong Y, Panicek D |title=Neoplastic pancreaticobiliary duct obstruction: evaluation with breath-hold MR cholangiopancreatography |journal=AJR Am J Roentgenol |volume=170 |issue=6 |pages=1491–5 |year=1998 |id=PMID 9609160}}</ref><ref>{{cite journal |author=Zidi S, Prat F, Le Guen O, Rondeau Y, Pelletier G |title=Performance characteristics of magnetic resonance cholangiography in the staging of malignant hilar strictures |journal=Gut |volume=46 |issue=1 |pages=103-6 |year=2000 |id=PMID 10601064}}</ref><ref>{{cite journal |author=Lee M, Park K, Shin Y, Yoon H, Sung K, Kim M, Lee S, Kang E |title=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 |journal=World J Surg |volume=27 |issue=3 |pages=278-83 |year=2003 |id=PMID 12607051}}</ref> 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.<ref>{{cite journal |author=Yeh T, Jan Y, Tseng J, Chiu C, Chen T, Hwang T, Chen M |title=Malignant perihilar biliary obstruction: magnetic resonance cholangiopancreatographic findings |journal=Am J Gastroenterol |volume=95 |issue=2 |pages=432-40 |year=2000 |id=PMID 10685746}}</ref><ref>{{cite journal |author=Freeman M, Sielaff T |title=A modern approach to malignant hilar biliary obstruction |journal=Rev Gastroenterol Disord |volume=3 |issue=4 |pages=187–201 |year=2003 |id=PMID 14668691}}</ref><ref>{{cite journal |author=Szklaruk J, Tamm E, Charnsangavej C |title=Preoperative imaging of biliary tract cancers |journal=Surg Oncol Clin N Am |volume=11 |issue=4 |pages=865-76 |year=2002 |id=PMID 12607576}}</ref>
<br clear="left"/>
 
===Surgery===
[[Surgery|Surgical exploration]] may be necessary to obtain a suitable [[biopsy]] and to accurately [[cancer staging|stage]] a 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.<ref>{{cite journal |author=Weber S, DeMatteo R, Fong Y, Blumgart L, Jarnagin W |title=Staging laparoscopy in patients with extrahepatic biliary carcinoma. Analysis of 100 patients |journal=Ann Surg |volume=235 |issue=3 |pages=392-9 |year=2002 |id=PMID 11882761}}</ref><ref>{{cite journal |author=Callery M, Strasberg S, Doherty G, Soper N, Norton J |title=Staging laparoscopy with laparoscopic ultrasonography: optimizing resectability in hepatobiliary and pancreatic malignancy |journal=J Am Coll Surg |volume=185 |issue=1 |pages=33-9 |year=1997 |id=PMID 9208958}}</ref> Surgery is also the only curative option for cholangiocarcinoma, although it is limited to patients with early-stage disease (see below).
 
===Pathology===
Histologically, cholangiocarcinomas are classically well to moderately differentiated.  [[Immunohistochemistry]] is useful in the diagnosis and can be used to differentiate a cholangiocarcinoma primary tumour from metastasis of most other gastrointestinal tumours.<ref>{{cite journal |author=Länger F, von Wasielewski R, Kreipe HH |title=[The importance of immunohistochemistry for the diagnosis of cholangiocarcinomas] |language=German |journal=Pathologe |volume=27 |issue=4 |pages=244-50 |year=2006 |pmid=16758167}}</ref>  Cytological scrappings are often non-diagnostic.<ref>Darwin PE, Kennedy A. Cholangiocarcinoma. eMedicine.com. URL: [http://www.emedicine.com/med/topic343.htm http://www.emedicine.com/med/topic343.htm]. Accessed on: May 5, 2007.</ref>
 
==Staging==
 
Although there are at least 3 [[cancer staging|staging systems]] for cholangiocarcinoma (e.g.  Bismuth, Blumgart, [[American Joint Committee on Cancer]]) none have been shown to be useful in predicting survival.<ref>{{cite journal |author=Zervos E, Osborne D, Goldin S, Villadolid D, Thometz D, Durkin A, Carey L, Rosemurgy A |title=Stage does not predict survival after resection of hilar cholangiocarcinomas promoting an aggressive operative approach |journal=Am J Surg |volume=190 |issue=5 |pages=810-5 |year=2005 |id=PMID 16226963}}</ref> The most important staging issue is whether the tumor can be [[resection|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.<ref name="feldman"/>
 
General guidelines for operability include:<ref>{{cite journal |author=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 |title=Management of hilar cholangiocarcinoma: comparison of an American and a Japanese experience |journal=Ann Surg |volume=232 |issue=2 |pages=166-74 |year=2000 |id=PMID 10903592}}</ref><ref>{{cite journal |author=Rajagopalan V, Daines W, Grossbard M, Kozuch P |title=Gallbladder and biliary tract carcinoma: A comprehensive update, Part 1 |journal=Oncology (Williston Park) |volume=18 |issue=7 |pages=889-96 |year=2004 |id=PMID 15255172}}</ref>
 
*Absence of [[lymph node]] or liver [[metastasis|metastases]]
*Absence of involvement of the [[hepatic portal vein|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%&ndash;25%, although one series reported a [[five year survival rate|five year survival]] of 54% for patients with no involvement of the [[lymph node]]s.<ref>Studies of surgical outcomes in distal 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=Nagorney D, Donohue J, Farnell M, Schleck C, Ilstrup D |title=Outcomes after curative resections of cholangiocarcinoma |journal=Arch Surg |volume=128 |issue=8 |pages=871–7; discussion 877-9 |year=1993 |pmid=8393652}}
*{{cite journal |author=Jang J, Kim S, Park D, Ahn Y, Yoon Y, Choi M, Suh K, Lee K, Park Y |title=Actual long-term outcome of extrahepatic bile duct cancer after surgical resection |journal=Ann Surg |volume=241 |issue=1 |pages=77–84 |year=2005 |pmid=15621994}}
*{{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> 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> Perihilar cholangiocarcinomas (those occurring near where the bile ducts exit the liver) are least likely to be operable. When surgery is possible, they are generally treated with an aggressive approach often including [[cholecystectomy|removal of the gallbladder]] and potentially part of the liver. In patients with operable perihilar tumors, reported 5-year survival rates range from 20%&ndash;50%.<ref>Estimates of survival after surgery for perihilar cholangiocarcinoma include:
*{{cite journal |author=Burke E, Jarnagin W, Hochwald S, Pisters P, Fong Y, Blumgart L |title=Hilar Cholangiocarcinoma: patterns of spread, the importance of hepatic resection for curative operation, and a presurgical clinical staging system |journal=Ann Surg |volume=228 |issue=3 |pages=385-94 |year=1998 |pmid=9742921}}
*{{cite journal |author=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 |title=Management of hilar cholangiocarcinoma: comparison of an American and a Japanese experience |journal=Ann Surg |volume=232 |issue=2 |pages=166-74 |year=2000 |pmid=10903592}}
*{{cite journal |author=Chamberlain R, Blumgart L |title=Hilar cholangiocarcinoma: a review and commentary |journal=Ann Surg Oncol |volume=7 |issue=1 |pages=55–66 |year= |pmid=10674450}}
*{{cite journal |author=Washburn W, Lewis W, Jenkins R |title=Aggressive surgical resection for cholangiocarcinoma |journal=Arch Surg |volume=130 |issue=3 |pages=270-6 |year=1995 |pmid=7534059}}
*{{cite journal |author=Nagino M, Nimura Y, Kamiya J, Kanai M, Uesaka K, Hayakawa N, Yamamoto H, Kondo S, Nishio H |title=Segmental liver resections for hilar cholangiocarcinoma |journal=Hepatogastroenterology |volume=45 |issue=19 |pages=7–13 |year= |pmid=9496478}}
*{{cite journal |author=Rea D, Munoz-Juarez M, Farnell M, Donohue J, Que F, Crownhart B, Larson D, Nagorney D |title=Major hepatic resection for hilar cholangiocarcinoma: analysis of 46 patients |journal=Arch Surg |volume=139 |issue=5 |pages=514–23; discussion 523-5 |year=2004 |pmid=15136352}}
*{{cite journal |author=Launois B, Reding R, Lebeau G, Buard J |title=Surgery for hilar cholangiocarcinoma: French experience in a collective survey of 552 extrahepatic bile duct cancers |journal=J Hepatobiliary Pancreat Surg |volume=7 |issue=2 |pages=128-34 |year=2000 |pmid=10982604}}</ref>
 
The [[prognosis]] may be 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>


==Treatment==
==Treatment==
[[Cholangiocarcinoma medical therapy|Medical Therapy]] | [[Cholangiocarcinoma surgery|Surgery]] | [[Cholangiocarcinoma prevention|Prevention]]


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.<ref name="feldman"/>
==Case Studies==
[[Cholangiocarcinoma case study one|Case #1]]


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> 
{{Tumors}}
{{Tumor morphology}}


===Adjuvant chemotherapy and radiation therapy===
[[Category:Disease]]


If the tumor can be removed surgically, patients may receive [[adjuvant#oncology|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 [[excision|excised]]), adjuvant therapy is of uncertain benefit. Both positive<ref>{{cite journal |author=Todoroki T, Ohara K, Kawamoto T, Koike N, Yoshida S, Kashiwagi H, Otsuka M, Fukao K |title=Benefits of adjuvant radiotherapy after radical resection of locally advanced main hepatic duct carcinoma |journal=Int J Radiat Oncol Biol Phys |volume=46 |issue=3 |pages=581-7 |year=2000 |pmid=10701737}}</ref><ref>{{cite journal |author=Alden M, Mohiuddin M |title=The impact of radiation dose in combined external beam and intraluminal Ir-192 brachytherapy for bile duct cancer |journal=Int J Radiat Oncol Biol Phys |volume=28 |issue=4 |pages=945-51 |year=1994 |pmid=8138448}}</ref> and negative<ref name="nakeeb"/><ref>{{cite journal |author=González González D, Gouma D, Rauws E, van Gulik T, Bosma A, Koedooder C |title=Role of radiotherapy, in particular intraluminal brachytherapy, in the treatment of proximal bile duct carcinoma |journal=Ann Oncol |volume=10 Suppl 4 |issue= |pages=215-20 |year= |pmid=10436826}}</ref><ref>{{cite journal |author=Pitt H, Nakeeb A, Abrams R, Coleman J, Piantadosi S, Yeo C, Lillemore K, Cameron J |title=Perihilar cholangiocarcinoma. Postoperative radiotherapy does not improve survival |journal=Ann Surg |volume=221 |issue=6 |pages=788–97; discussion 797-8 |year=1995 |pmid=7794082}}</ref> results have been reported with adjuvant radiation therapy in this setting, and no prospective [[randomized controlled trial]]s have been conducted as of March 2007. Adjuvant chemotherapy appears to be ineffective in patients with completely resected tumors.<ref>{{cite journal |author=Takada T, Amano H, Yasuda H, Nimura Y, Matsushiro T, Kato H, Nagakawa T, Nakayama T |title=Is postoperative adjuvant chemotherapy useful for gallbladder carcinoma? A phase III multicenter prospective randomized controlled trial in patients with resected pancreaticobiliary carcinoma |journal=Cancer |volume=95 |issue=8 |pages=1685–95 |year=2002 |pmid=12365016}}</ref> The role of combined chemoradiotherapy in this setting is unclear. However, 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.<ref name="nccn">{{PDFlink|[http://www.nccn.org/professionals/physician_gls/PDF/hepatobiliary.pdf National Comprehensive Cancer Network (NCCN) guidelines on evaluation and treatment of hepatobiliary malignancies]|216&nbsp;[[Kibibyte|KiB]]<!-- application/pdf, 221777 bytes -->}}. Accessed [[March 13]] [[2007]].</ref>
[[Category:Rare cancers]]
[[Category:Rare diseases]]


===Treatment of advanced disease===
[[Category:Oncology]]
The majority of cases of cholangiocarcinoma present as unresectable disease.<ref>{{cite journal |author=Vauthey J, Blumgart L |title=Recent advances in the management of cholangiocarcinomas |journal=Semin. Liver Dis. |volume=14 |issue=2 |pages=109-14 |year=1994 |pmid=8047893}}</ref> If the tumor cannot be surgically removed, patients are often treated with [[palliation|palliative]] [[chemotherapy]] with or without [[radiotherapy]].  Chemotherapy has been shown in a [[randomized controlled trial]] to improve [[quality of life]] and extend survival in patients with inoperable cholangiocarcinoma.<ref>{{cite journal |author=Glimelius B, Hoffman K, Sjödén P, Jacobsson G, Sellström H, Enander L, Linné T, Svensson C |title=Chemotherapy improves survival and quality of life in advanced pancreatic and biliary cancer |journal=Ann Oncol |volume=7 |issue=6 |pages=593–600 |year=1996 |id=PMID 8879373}}</ref> There is no single chemotherapy regimen which is universally used, and enrollment in [[clinical trial]]s is often recommended when possible.<ref name="nccn"/> Chemotherapy agents used to treat cholangiocarcinoma include [[5-fluorouracil]] with [[leucovorin]],<ref>{{cite journal |author=Choi C, Choi I, Seo J, Kim B, Kim J, Kim C, Um S, Kim J, Kim Y |title=Effects of 5-fluorouracil and leucovorin in the treatment of pancreatic-biliary tract adenocarcinomas |journal=Am J Clin Oncol |volume=23 |issue=4 |pages=425-8 |year=2000 |pmid=10955877}}</ref> [[gemcitabine]] as a single agent,<ref>{{cite journal |author=Park J, Oh S, Kim S, Kwon H, Kim J, Jin-Kim H, Kim Y |title=Single-agent gemcitabine in the treatment of advanced biliary tract cancers: a phase II study |journal=Jpn J Clin Oncol |volume=35 |issue=2 |pages=68–73 |year=2005 |pmid=15709089}}</ref> or gemcitabine plus [[cisplatin]],<ref>{{cite journal |author=Giuliani F, Gebbia V, Maiello E, Borsellino N, Bajardi E, Colucci G |title=Gemcitabine and cisplatin for inoperable and/or metastatic biliary tree carcinomas: a multicenter phase II study of the Gruppo Oncologico dell'Italia Meridionale (GOIM) |journal=Ann Oncol |volume=17 Suppl 7 |issue= |pages=vii73-vii77 |year= |pmid=16760299}}</ref> [[irinotecan]],<ref>{{cite journal |author=Bhargava P, Jani C, Savarese D, O'Donnell J, Stuart K, Rocha Lima C |title=Gemcitabine and irinotecan in locally advanced or metastatic biliary cancer: preliminary report |journal=Oncology (Williston Park) |volume=17 |issue=9 Suppl 8 |pages=23-6 |year=2003 |pmid=14569844}}</ref> or [[capecitabine]].<ref>{{cite journal |author=Knox J, Hedley D, Oza A, Feld R, Siu L, Chen E, Nematollahi M, Pond G, Zhang J, Moore M |title=Combining gemcitabine and capecitabine in patients with advanced biliary cancer: a phase II trial |journal=J Clin Oncol |volume=23 |issue=10 |pages=2332–8 |year=2005 |pmid=15800324}}</ref> A small pilot study suggested possible benefit from the [[tyrosine kinase]] inhibitor [[erlotinib]] in patients with advanced cholangiocarcinoma.<ref>{{cite journal |author=Philip P, Mahoney M, Allmer C, Thomas J, Pitot H, Kim G, Donehower R, Fitch T, Picus J, Erlichman C |title=Phase II study of erlotinib in patients with advanced biliary cancer |journal=J Clin Oncol |volume=24 |issue=19 |pages=3069–74 |year=2006 |pmid=16809731}}</ref>
[[Category:Types of cancer]]
 
[[Photodynamic therapy]], an experimental approach in which patients are injected with a light-sensitizing agent and light is then applied [[endoscopy|endoscopically]] directly to the tumor, has shown promising results compared to supportive care in two small [[randomized controlled trial]]s. However, its ultimate role in the management of cholangiocarcinoma is unclear at present.<ref>{{cite journal |author=Ortner M, Caca K, Berr F, Liebetruth J, Mansmann U, Huster D, Voderholzer W, Schachschal G, Mössner J, Lochs H |title=Successful photodynamic therapy for nonresectable cholangiocarcinoma: a randomized prospective study |journal=Gastroenterology |volume=125 |issue=5 |pages=1355–63 |year=2003 |pmid=14598251}}</ref><ref>{{cite journal |author=Zoepf T, Jakobs R, Arnold J, Apel D, Riemann J |title=Palliation of nonresectable bile duct cancer: improved survival after photodynamic therapy |journal=Am J Gastroenterol |volume=100 |issue=11 |pages=2426–30 |year=2005 |pmid=16279895}}</ref>
 
==External links==
* [http://www.cancer.org/docroot/CRI/CRI_2_3x.asp?dt=69 American Cancer Society Detailed Guide to Bile Duct Cancer].
* [http://www.cancer.gov/cancertopics/pdq/treatment/bileduct/Patient/ Patient information on extrahepatic bile duct tumors], from the [[National Cancer Institute]].
* [http://www.cholangiocarcinoma.org/ The Cholangiocarcinoma Foundation]: a resource for patients, friends, caregivers and loved ones.
 
== References ==
{{refbegin|2}}
1. Landis S, Murray T, Bolden S, Wingo P. "Cancer statistics, 1998". CA Cancer J Clin 48 (1): 6–29. PMID 9449931.
 
2. Patel T. "Worldwide trends in mortality from biliary tract malignancies". BMC Cancer 2: 10. PMID 11991810.
 
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.
 
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.
 
5.Feldman, pp. 1493–1496.
 
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.
 
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.
 
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.
 
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.
* 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.
* 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.
* 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.
 
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.
 
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.
* 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.
* 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.
 
14.Watanapa P (1996). "Cholangiocarcinoma in patients with opisthorchiasis". Br J Surg 83 (8): 1062–64. PMID 8869303.
 
15.Watanapa P, Watanapa W (2002). "Liver fluke-associated cholangiocarcinoma". Br J Surg 89 (8): 962-70. PMID 12153620.
 
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.
 
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.
 
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.
 
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.
 
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.
 
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.
 
22. Dayton M, Longmire W, Tompkins R (1983). "Caroli's Disease: a premalignant condition?". Am J Surg 145 (1): 41-8. PMID 6295196.
 
23. Mecklin J, Järvinen H, Virolainen M (1992). "The association between cholangiocarcinoma and hereditary nonpolyposis colorectal carcinoma". Cancer 69 (5): 1112–4. PMID 1310886.
 
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.
 
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.
 
26. Su C, Shyr Y, Lui W, P'Eng F (1997). "Hepatolithiasis associated with cholangiocarcinoma". Br J Surg 84 (7): 969-73. PMID 9240138.
 
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.
 
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.
 
29. Zhu A, Lauwers G, Tanabe K (2004). "Cholangiocarcinoma in association with Thorotrast exposure". J Hepatobiliary Pancreat Surg 11 (6): 430-3. PMID 15619021.
 
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.
 
31. Roskams T (2006). "Liver stem cells and their implication in hepatocellular and cholangiocarcinoma". Oncogene 25 (27): 3818–22. PMID 16799623.
 
32.Liu C, Wang J, Ou Q (2004). "Possible stem cell origin of human cholangiocarcinoma". World J Gastroenterol 10 (22): 3374–6. PMID 15484322.
 
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.
 
34. Sirica A (2005). "Cholangiocarcinoma: molecular targeting strategies for chemoprevention and therapy". Hepatology 41 (1): 5–15. PMID 15690474.
 
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.
 
36.Gores G (2003). "Cholangiocarcinoma: current concepts and insights". Hepatology 37 (5): 961-9. PMID 12717374.
 
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.
 
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.
 
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:
* Nehls O, Gregor M, Klump B (2004). "Serum and bile markers for cholangiocarcinoma". Semin Liver Dis 24 (2): 139-54. PMID 15192787.
* 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.
* 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.
* 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.
 
40.Saini S (1997). "Imaging of the hepatobiliary tract". N Engl J Med 336 (26): 1889–94. PMID 9197218.
 
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.
 
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.
 
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.
 
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.
 
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.
 
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.
 
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.
 
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.
 
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.
 
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.
 
51.Freeman M, Sielaff T (2003). "A modern approach to malignant hilar biliary obstruction". Rev Gastroenterol Disord 3 (4): 187–201. PMID 14668691.
 
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.
 
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.
 
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.
 
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.
 
56. Darwin PE, Kennedy A. Cholangiocarcinoma. eMedicine.com. URL: http://www.emedicine.com/med/topic343.htm. Accessed on: May 5, 2007.
 
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.
 
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.
 
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.
 
60.Studies of surgical outcomes in distal cholangiocarcinoma include:
* 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.
* 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.
* 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.
* 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.
* 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.
 
61.Studies of outcome in intrahepatic cholangiocarcinoma include:
* 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.
* 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.
* 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.
* 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.
* 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.
 
62.Estimates of survival after surgery for perihilar cholangiocarcinoma include:
* 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.
* 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.
* Chamberlain R, Blumgart L. "Hilar cholangiocarcinoma: a review and commentary". Ann Surg Oncol 7 (1): 55–66. PMID 10674450.
* Washburn W, Lewis W, Jenkins R (1995). "Aggressive surgical resection for cholangiocarcinoma". Arch Surg 130 (3): 270-6. PMID 7534059.
* 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.
* 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.
* 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.
 
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.
 
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.
 
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.
 
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.
 
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.
 
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.
 
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.
 
70. González González D, Gouma D, Rauws E, van Gulik T, Bosma A, Koedooder C. "Role of radiotherapy, in particular intraluminal brachytherapy, in the treatment of proximal bile duct carcinoma". Ann Oncol 10 Suppl 4: 215-20. PMID 10436826.
 
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.
 
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.
 
73.National Comprehensive Cancer Network (NCCN) guidelines on evaluation and treatment of hepatobiliary malignanciesPDF (216 KiB). Accessed March 13, 2007.
 
74. Vauthey J, Blumgart L (1994). "Recent advances in the management of cholangiocarcinomas". Semin. Liver Dis. 14 (2): 109-14. PMID 8047893.
 
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.
 
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.
 
77.Park J, Oh S, Kim S, Kwon H, Kim J, Jin-Kim H, Kim Y (2005). "Single-agent gemcitabine in the treatment of advanced biliary tract cancers: a phase II study". Jpn J Clin Oncol 35 (2): 68–73. PMID 15709089.
 
78. Giuliani F, Gebbia V, Maiello E, Borsellino N, Bajardi E, Colucci G. "Gemcitabine and cisplatin for inoperable and/or metastatic biliary tree carcinomas: a multicenter phase II study of the Gruppo Oncologico dell'Italia Meridionale (GOIM)". Ann Oncol 17 Suppl 7: vii73-vii77. PMID 16760299.
 
79. Bhargava P, Jani C, Savarese D, O'Donnell J, Stuart K, Rocha Lima C (2003). "Gemcitabine and irinotecan in locally advanced or metastatic biliary cancer: preliminary report". Oncology (Williston Park) 17 (9 Suppl 8): 23-6. PMID 14569844.
 
80. Knox J, Hedley D, Oza A, Feld R, Siu L, Chen E, Nematollahi M, Pond G, Zhang J, Moore M (2005). "Combining gemcitabine and capecitabine in patients with advanced biliary cancer: a phase II trial". J Clin Oncol 23 (10): 2332–8. PMID 15800324.
 
81.Philip P, Mahoney M, Allmer C, Thomas J, Pitot H, Kim G, Donehower R, Fitch T, Picus J, Erlichman C (2006). "Phase II study of erlotinib in patients with advanced biliary cancer". J Clin Oncol 24 (19): 3069–74. PMID 16809731.
 
82.Ortner M, Caca K, Berr F, Liebetruth J, Mansmann U, Huster D, Voderholzer W, Schachschal G, Mössner J, Lochs H (2003). "Successful photodynamic therapy for nonresectable cholangiocarcinoma: a randomized prospective study". Gastroenterology 125 (5): 1355–63. PMID 14598251.
 
83.Zoepf T, Jakobs R, Arnold J, Apel D, Riemann J (2005). "Palliation of nonresectable bile duct cancer: improved survival after photodynamic therapy". Am J Gastroenterol 100 (11): 2426–30. PMID 16279895.
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Suveenkrishna Pothuru, M.B,B.S. [2]

Synonyms and keywords: Bile duct cancer; Bile duct carcinoma; Cancer of bile duct; Intrahepatic cholangiocarcinoma; Extrahepatic cholangiocarcinoma; Perihilar cholangiocarcinoma; Hilar cholangiocarcinoma

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