Overview of Cholangiocarcinoma

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something for you if you like to read about CCA.

Overview of Cholangiocarcinoma for ipad users

During liver development, hepatoblasts differentiate into hepatocytes and biliary cells which delineate the bile ducts. More than 90% of the bile duct cancer (cholangiocarcinoma) are well to moderately differentiated adenocarcinomas.
Cholangiocarcinoma (CCA) is an epithelial cancer of the bile duct that can be intrahepatic (20-25%) or extrahepatic such as perihilar tumor(50%) and distal bile duct cancer(20-25%). CCA represented about 13% of primary liver cancers and is the second most common primary liver after hepatocellular carcinoma. The prevalance of liver and intrahepatic CCA (ICCA) shows highest in China for men(95 per 100,000 )and Thailand for women( 35 per 100,000);
In general, CCA are rare in Europe and the USA, accounting for % of all GI tumors. In the United States, the incidence of CCA is approximately 7,000 new cases/year .In UK,it is about 1,500 cases/year ;in Japan, according to the health ministry,there were 13,000 deaths in 2010 alone and in South Korea, it is about 3,500 new cases per year.For unknown reasons the incidence of intrahepatic CCA occurrence has been increasing worldwide from North America, Europe, Asia and Australia; Country like Italy reported a 40-fold increase in intrahepatic CCA mortality from 1980-2003. In contrast, the mortality rate of extrahepatic CCA (ECCA) is declining worldwide.

The most common risk factors for patient in United States and Europe are the inflammatory disease like primary sclerosing cholangitis (25-30%), ulcerative colitis and congenital choledochal cysts. In Asia, and other parts of the world like Middle East, parasitic infections, hepatitis B,C infections, HIV, biliary tract stones diseases ; chemical agents like Thorotrast, dioxin, alcohol, early formulary of oral contraceptive,isoniazid and smoking; age>65(range:20-90’s) ,diabetes and obesity are known risk factors for CCA.
By the time the symptoms of CCA (Jaundice, itching, right upper abdominal pain, weight loss ,light color stools , dark urine) show up, normally it will too late for surgery. Surgery like resection and orthotopic liver transplant provide the only possible cure ; stage III and IV CCA are generally considered unresectable. Clinical staging is fundamental in pre-surgical evaluation using MRCP,ERCP, EUS, Doppler US, CT, MRI and PET. PET scan changes the surgical management in a third (33%) of patients. In a large study, the resectability rates for intrahepatic , perihilar and distal lesions were 60%, 91% and 56%.

For ICCA patients,five-year survival rates after resection is around 22-44% and correlate with R0 margin (clear margin), lymph node involvement and vascular invasion. Recurrence is very common(>75%) after liver resection. Re-resection, TACE, RFA , SBRT, and radioembolization are radiological approach for treatment while chemotherapy with Gemcitabine ,5 FU(including capecitabine,S1), cisplatin,carboplatin,oxaliplatin , irinotecan, paclitaxel ,docetaxel ; molecularly targeted agents like sorafenib erlotinib ,cetuximab and bevacizumab ,and the combination using of them or joining clinical studies are other choices to extend the life of ICCA patients.

For ECCA patients, biliary drainage either by endoscopic or percutaneous stenting will provide relief of the biliary obstruction. Recurrence after resection are common in ECCA patients. Systemic treatment are the same as ICCA above; radiation therapy such as brachytherapy,EBRT, PDT, SBRT, and the more advance tomotherapy IMRT and Robotic Linac IMRT ; orthotopic liver transplant ,and clinical trials are acceptable to prolong life expectancy. Five-year survival rate for ECCA is around 20-50% and for liver transplant patient (68%). If untreated, life expectancy is about 4-12 months.
Among patients who undergo resection for CCA, long term outcomes depending on the histologic margin, lymph node involvement , location ,
number and stage of the lesions, the extent of the surgery, the general health of the patient and treatment-related complications. The benefit of adjuvant chemotherapy and /or radiation therapy is controversial at best.

Quantity vs the quality of life should be always considered for the overall benefit of the patient. Multimodality approaches should be considered to improve the outcome for both the resected patients and unresectable CCA patients.Above all ,since surgery provides the only possible cure . Establishment of effective early detection tests using biomarkers and development of new molecularly targeted agents are urgently needed to provide more effective treatment with less adverse reactions to the CCA patients.

References:
1. Cornelia Braicu et al .Molecular markers in the Pathogenesis of CCA :Potential for Early Detection.
Gastroenterology Res,Vol 2.No. 3,Jun 2009
2. Christopher Anderson,MD et al. Treatment of localized Cholangiocarcinoma: surgical management and adjuvant therapy. Literature review version 19.1: May,2011.
3. Tushar Patel. Cholangiocarcinoma-controversies and challenges: Gastroenterology & Hepatology vol.8,Apr.2011
4. Manuela Gatto, domenico Alvaro.et al> New Insights on cholangiocarcinoma: World J Gastrointest oncol. 2010 March 15 ;2(3): 136-145.
5. Murad Aljiffry,Alhawsawi Abdulelah et al. Evidnece-based approach to Cholangiocarcinoma: a systematic Review of the Current Literature: doi:10.1016/j.jamcollsurg.2008.09.007.
6. National Center Center,Korea,Republic of.
7. Michael Tedesco,Univ.of Rochester medical center web site 3/5/2012
8. http://www.yomiuri.co.jp/dy/national/T120711003755.htm
9. http://www.cholangiocarcinoma.org/punbb/viewtopic.php?id=7730
10. http://www.cholangiocarcinoma.org/punbb/viewtopic.php?id=8542
God bless.