Cholangiocarcinoma natural history, complications and prognosis: Difference between revisions

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{{Cholangiocarcinoma}}
{{Cholangiocarcinoma}}
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{{CMG}}; {{AE}} {{F.K}}, {{PSK}}


==Overview==
==Overview==
==Complications==
The symptoms of cholangiocarcinoma usually develop in the fourth decade of life, and start with symptoms such as [[abdominal pain]], [[jaundice]] and [[fever]]. Common complications of cholangiocarcinoma [[infection]], [[liver failure]], [[Metastasis|tumor metastasis]].
Common complications of cholangiocarcinoma include:
* Infection
* Liver failure
* Tumor metastasis
Pattern of metastatic spread include:<ref name=radio>Cholangiocarcinoma. Radiopaedia. http://radiopaedia.org/articles/cholangiocarcinoma</ref>
*Intrahepatic vascular involvement with numerous local metastases
*Metastasis to regional lymphnodes
*Hematogenous spread to lungs, bones, adranals, and brain


==Prognosis==
==Natural History, Complications, and Prognosis==
The most important factor in prognosis of cholangiocarcinoma is whether or not the tumor is able to be resected. Even with resection, prognosis is poor with 5-year survival of only 10-44%.<ref name=radio>Cholangiocarcinoma. Radiopaedia. http://radiopaedia.org/articles/cholangiocarcinoma</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>{{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> 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.


===Extent of the tumor===
===Natural history===
*Prognosis is somewhat better for people with early stage cancer than for people with advanced stage cancer. Patients with multiple tumors, larger tumors and tumors that have spread to nearby blood vessels or lymph nodes tend to have a poor outcome.
The symptoms of cholangiocarcinoma usually develop in the fourth decade of life, and start with symptoms such as [[abdominal pain]], [[jaundice]] and [[fever]].  


===Resectability===
===Complications===
Tumors that can be completely removed by surgery (resectable) have a more favorable prognosis than tumors that cannot be removed by surgery (unresectable). Palliative chemotherapy, radiotherapy, and photodynamic therapy have been relatively ineffective in treating non-operable cholangiocarcinomas, with a 5-year survival <5% without resection, due to the refractoriness of these tumors:<ref name="Macias2014">{{cite journal|last1=Macias|first1=Rocio I. R.|title=Cholangiocarcinoma: Biology, Clinical Management, and Pharmacological Perspectives|journal=ISRN Hepatology|volume=2014|year=2014|pages=1–13|issn=2314-4041|doi=10.1155/2014/828074}}</ref>
Common complications of cholangiocarcinoma include:<ref name="pmid21460876">{{cite journal |vauthors=Patel T |title=Cholangiocarcinoma--controversies and challenges |journal=Nat Rev Gastroenterol Hepatol |volume=8 |issue=4 |pages=189–200 |year=2011 |pmid=21460876 |pmc=3888819 |doi=10.1038/nrgastro.2011.20 |url=}}</ref>
*'''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 nodes]].<ref>Studies of surgical outcomes in distal cholangiocarcinoma include:
* [[Infection]]
*{{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}}
* [[Liver failure]]
*{{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}}
* [[Metastasis|Tumor metastasis]]
*{{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]] 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>
===Surgical margins===
*The best prognostic factors are resection of tumor-free surgical margin without lymph node invasion, while tumor diameter, histology, and differentiation are poor predictors of good outcome with 5-year survival rates varying from 20 to 60%.<ref name="Macias2014">{{cite journal|last1=Macias|first1=Rocio I. R.|title=Cholangiocarcinoma: Biology, Clinical Management, and Pharmacological Perspectives|journal=ISRN Hepatology|volume=2014|year=2014|pages=1–13|issn=2314-4041|doi=10.1155/2014/828074}}</ref>


*The 5-year survival for resection of tumor-free surgical margins of extrahepatic cholangiocarcinomas is about 30%, with recurrence observed in the majority of patients due to disseminated tumors or the de novo formation of tumors in the already oncogenic liver tissue.
===Prognosis===
*Depending on the extent of the cholangiocarcinoma at the time of diagnosis, the [[prognosis]] may vary. However, the prognosis is generally regarded as poor with 5-year survival of only 10-44%.<ref name="pmid17457168">{{cite journal |vauthors=DeOliveira ML, Cunningham SC, Cameron JL, Kamangar F, Winter JM, Lillemoe KD, Choti MA, Yeo CJ, Schulick RD |title=Cholangiocarcinoma: thirty-one-year experience with 564 patients at a single institution |journal=Ann. Surg. |volume=245 |issue=5 |pages=755–62 |year=2007 |pmid=17457168 |pmc=1877058 |doi=10.1097/01.sla.0000251366.62632.d3 |url=}}</ref>
*The prognosis may be worse for patients with [[primary sclerosing cholangitis]] who develop cholangiocarcinoma.
*The most important factor in [[prognosis]] of cholangiocarcinoma is whether or not the tumor is able to be resected.


Liver transplantation performed after neoadjuvant chemoradiation in selected patients, due to organ shortage, has afforded a very good disease-free 5-year survival (>80%), providing a better outcome and fewer recurrences than conventional resection.
====Extent of the tumor====
*Patients with multiple tumors, larger tumors and tumors that have spread to nearby blood vessels or [[Lymph node|lymph nodes]] have a poor outcome.
 
====Resectability====
[[Tumors]] that can be completely removed by [[surgery]] (resectable) have a better [[prognosis]] than tumors that cannot be removed by [[surgery]] (unresectable).
*'''Distal cholangiocarcinoma:''' Long-term [[survival rates]] range from 15%-25%.<ref name="pmid27554480">{{cite journal |vauthors=Kim BH, Kim K, Chie EK, Kwon J, Jang JY, Kim SW, Oh DY, Bang YJ |title=Long-Term Outcome of Distal Cholangiocarcinoma after Pancreaticoduodenectomy Followed by Adjuvant Chemoradiotherapy: A 15-Year Experience in a Single Institution |journal=Cancer Res Treat |volume=49 |issue=2 |pages=473–483 |year=2017 |pmid=27554480 |pmc=5398409 |doi=10.4143/crt.2016.166 |url=}}</ref>
*'''Intrahepatic cholangiocarcinoma:'''  Survival estimates after surgery ranging from 22%-66%.<ref name="pmid19294467">{{cite journal |vauthors=Guglielmi A, Ruzzenente A, Campagnaro T, Pachera S, Valdegamberi A, Nicoli P, Cappellani A, Malfermoni G, Iacono C |title=Intrahepatic cholangiocarcinoma: prognostic factors after surgical resection |journal=World J Surg |volume=33 |issue=6 |pages=1247–54 |year=2009 |pmid=19294467 |doi=10.1007/s00268-009-9970-0 |url=}}</ref>
*'''Perihilar cholangiocarcinoma:''' 5 years survival rates range from 20-50%.<ref name="pmid18057991">{{cite journal |vauthors=Sano T, Shimada K, Sakamoto Y, Ojima H, Esaki M, Kosuge T |title=Prognosis of perihilar cholangiocarcinoma: hilar bile duct cancer versus intrahepatic cholangiocarcinoma involving the hepatic hilus |journal=Ann. Surg. Oncol. |volume=15 |issue=2 |pages=590–9 |year=2008 |pmid=18057991 |doi=10.1245/s10434-007-9687-y |url=}}</ref>
 
====Surgical margins====
*The best prognostic factors are resection of tumor-free surgical margin without [[lymph node]] [[invasion]].<ref name="pmid22042474">{{cite journal |vauthors=Farges O, Fuks D, Boleslawski E, Le Treut YP, Castaing D, Laurent A, Ducerf C, Rivoire M, Bachellier P, Chiche L, Nuzzo G, Regimbeau JM |title=Influence of surgical margins on outcome in patients with intrahepatic cholangiocarcinoma: a multicenter study by the AFC-IHCC-2009 study group |journal=Ann. Surg. |volume=254 |issue=5 |pages=824–29; discussion 830 |year=2011 |pmid=22042474 |doi=10.1097/SLA.0b013e318236c21d |url=}}</ref>
*Tumor diameter, [[histology]], and differentiation are poor predictors of good outcome with 5-year survival rates varying from 20 to 60%.<ref name="Macias2014">{{cite journal|last1=Macias|first1=Rocio I. R.|title=Cholangiocarcinoma: Biology, Clinical Management, and Pharmacological Perspectives|journal=ISRN Hepatology|volume=2014|year=2014|pages=1–13|issn=2314-4041|doi=10.1155/2014/828074}}</ref>
*For [[extrahepatic cholangiocarcinoma]], 5 year survival rate is approximately 30% after resection of tumor-free surgical margins. Majority of patients have recurrence due to following reasons:
**Disseminated [[tumors]]
**Formation of new tumors in previously oncogenic [[liver]] tissue


==References==
==References==

Latest revision as of 14:57, 13 February 2018

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Farima Kahe M.D. [2], Suveenkrishna Pothuru, M.B,B.S. [3]

Overview

The symptoms of cholangiocarcinoma usually develop in the fourth decade of life, and start with symptoms such as abdominal pain, jaundice and fever. Common complications of cholangiocarcinoma infection, liver failure, tumor metastasis.

Natural History, Complications, and Prognosis

Natural history

The symptoms of cholangiocarcinoma usually develop in the fourth decade of life, and start with symptoms such as abdominal pain, jaundice and fever.

Complications

Common complications of cholangiocarcinoma include:[1]

Prognosis

  • Depending on the extent of the cholangiocarcinoma at the time of diagnosis, the prognosis may vary. However, the prognosis is generally regarded as poor with 5-year survival of only 10-44%.[2]
  • The prognosis may be worse for patients with primary sclerosing cholangitis who develop cholangiocarcinoma.
  • The most important factor in prognosis of cholangiocarcinoma is whether or not the tumor is able to be resected.

Extent of the tumor

  • Patients with multiple tumors, larger tumors and tumors that have spread to nearby blood vessels or lymph nodes have a poor outcome.

Resectability

Tumors that can be completely removed by surgery (resectable) have a better prognosis than tumors that cannot be removed by surgery (unresectable).

  • Distal cholangiocarcinoma: Long-term survival rates range from 15%-25%.[3]
  • Intrahepatic cholangiocarcinoma: Survival estimates after surgery ranging from 22%-66%.[4]
  • Perihilar cholangiocarcinoma: 5 years survival rates range from 20-50%.[5]

Surgical margins

  • The best prognostic factors are resection of tumor-free surgical margin without lymph node invasion.[6]
  • Tumor diameter, histology, and differentiation are poor predictors of good outcome with 5-year survival rates varying from 20 to 60%.[7]
  • For extrahepatic cholangiocarcinoma, 5 year survival rate is approximately 30% after resection of tumor-free surgical margins. Majority of patients have recurrence due to following reasons:
    • Disseminated tumors
    • Formation of new tumors in previously oncogenic liver tissue

References

  1. ↑ Patel T (2011). "Cholangiocarcinoma--controversies and challenges". Nat Rev Gastroenterol Hepatol. 8 (4): 189–200. doi:10.1038/nrgastro.2011.20. PMC 3888819. PMID 21460876.
  2. ↑ DeOliveira ML, Cunningham SC, Cameron JL, Kamangar F, Winter JM, Lillemoe KD, Choti MA, Yeo CJ, Schulick RD (2007). "Cholangiocarcinoma: thirty-one-year experience with 564 patients at a single institution". Ann. Surg. 245 (5): 755–62. doi:10.1097/01.sla.0000251366.62632.d3. PMC 1877058. PMID 17457168.
  3. ↑ Kim BH, Kim K, Chie EK, Kwon J, Jang JY, Kim SW, Oh DY, Bang YJ (2017). "Long-Term Outcome of Distal Cholangiocarcinoma after Pancreaticoduodenectomy Followed by Adjuvant Chemoradiotherapy: A 15-Year Experience in a Single Institution". Cancer Res Treat. 49 (2): 473–483. doi:10.4143/crt.2016.166. PMC 5398409. PMID 27554480.
  4. ↑ Guglielmi A, Ruzzenente A, Campagnaro T, Pachera S, Valdegamberi A, Nicoli P, Cappellani A, Malfermoni G, Iacono C (2009). "Intrahepatic cholangiocarcinoma: prognostic factors after surgical resection". World J Surg. 33 (6): 1247–54. doi:10.1007/s00268-009-9970-0. PMID 19294467.
  5. ↑ Sano T, Shimada K, Sakamoto Y, Ojima H, Esaki M, Kosuge T (2008). "Prognosis of perihilar cholangiocarcinoma: hilar bile duct cancer versus intrahepatic cholangiocarcinoma involving the hepatic hilus". Ann. Surg. Oncol. 15 (2): 590–9. doi:10.1245/s10434-007-9687-y. PMID 18057991.
  6. ↑ Farges O, Fuks D, Boleslawski E, Le Treut YP, Castaing D, Laurent A, Ducerf C, Rivoire M, Bachellier P, Chiche L, Nuzzo G, Regimbeau JM (2011). "Influence of surgical margins on outcome in patients with intrahepatic cholangiocarcinoma: a multicenter study by the AFC-IHCC-2009 study group". Ann. Surg. 254 (5): 824–29, discussion 830. doi:10.1097/SLA.0b013e318236c21d. PMID 22042474.
  7. ↑ Macias, Rocio I. R. (2014). "Cholangiocarcinoma: Biology, Clinical Management, and Pharmacological Perspectives". ISRN Hepatology. 2014: 1–13. doi:10.1155/2014/828074. ISSN 2314-4041.

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