Biliary tract cancer

Accounts for 3-4% of gastrointestinal tract malignancies.

Affects up to 12,000 people annually in the US.

Invasive adenocarcinomas arising from the epithelial lining from the gall bladder and intrahepatic and extra hepatic bile ducts.

Biliary tract cancers include: gallbladder cancer, intra hepatic cholangiocarcinoma and extra hepatic cholangiocarcinoma.

Extrahepatic cholangiocarcinoma includes both hilar (Klatskin tumor), and distas..

Five-year survival rate of only 10%.

Incidence increasing in the U.S., particularly driven by an increase in cases of intrahepatic cholangiocarcinoma.

Among women there is a 26 fold variation in biliary tract cancer mortality worldwide, ranging from 0.8 deaths per hundred thousand in South Africa to 21.2 per hundred thousand in Chile.

Increased incidence in Native Americans and Hispanic women.

In American Indians in New Mexico, gallbladder cancer mortality rates are 8.9 for 100,000 surpassing those for breast and pancreatic cancers.

Cholangiocarcinoma occurs more frequently and seventh decade of life and is more common in men, while with gallbladder carcinoma the median age of onset is 65 years and is more common in women.

Highest incidence in Pakistan, India, Korea, Japan Eastern Europe and some countries in South America.

Common problem in the northern part of India in females.

Chile and Bolivia also areas of high incidence.

Tumors originate from the epithelium of the gallbladder and bile ducts.

More than 90% of biliary tract tumors are well-differentiated, mucin producing adenocarcinoma is while squamous cell and small cell carcinomas occur less frequently.

Incidence in the Western world is 1-2 case 100,000.

Incidence in Asia in South America more frequently at 96 cases per 100,000.

Approximately 10 to 40% of patients are eligible for surgical resection.

Median survival for patients with unresectable disease is 2-4 months, with fewer than 5% surviving one year.

Biliary tract cancers frequently arise from chronic inflammation, injury, reparative biliary epithelial cell proliferation that occurs with sclerosing cholangitis, or hepatolithiasis:Indicating that chronic inflammation, cellular injury in the bile ducts, and partial biliary tract obstruction or fundamental to causing cholangiocarcinoma.

Common sites of metastasis of BTC’s include: liver, lymph nodes, and lungs.

Nodal metastases tend to occur early and biliary tract cancers with only 10% of patients presenting with early stage, resectable incurable disease.

Median survival range from 4-11 months, compared with patients with mainly cholangiocarcinomas which have median survivals of 15-16 months suggesting a difference in the biology of the 2 lesions.

For the minority of patients with resectable disease, surgical resection with negative margins and liver transplantation only potentials for cure.

Patients who have a R0, microscopically negative margin, resection have a five-year survival rate of 10-62% (Aljiffry M et al).

Patients with R1, microscopically positive margins, and R2 resections with macroscopic residual disease are associated with the five-year survival rates of 0%.

Gemzar plus carboplatin at an overall median survival of 9.5 months with a response rate of 30.8% (Sharma A et al).

Surgical resection associated complications include bile leakage, intra-abdominal abscess and liver failure.

Median survival rarely exceeds 6 months.

Characterized by local spread, extensive nodal disease, vascular encasement and distant metastases.

1 and 2 year survivals 25% and 13%, respectively.

Long term survival uncommon.

Patients with unresectable perihilar or intrahepatic cholangiocarcinoma, orthotopic liver transplantation has potential for cure.

Gallbladder carcinoma has a worse survival compared with cholangiocarcinoma with a better response to chemotherapy.

Gallbladder carcinoma tends to develop distant metastases after surgical treatment, while cholangiocarcinoma is more likely to recur locally.

Aggressive disease and resistant to chemotherapy with response rates from 0-25%.

Most patients present with advanced disease, but long-term survival rates may be as high as 80% for the rare stage I patient with surgical resection.

Surgery provides only avenue of cure but most patients have advanced disease at the time of diagnosis.

Chemotherapy has not been shown to increase survival.

5-FU response rate 10-15%.

Molecular profiling has increased and provides greater opportunities for targeted therapy with the findings of targeted FGFR2, IDH 1, and BRAF mutations.

HER-2 neu positive in more than 20% of lesions.

Combination therapy with gemcitabine and cis-platinum is presently the standard of care for advanced biliary tract cancers.

The addition of durvalummab to gemcitabine/cisplatinum has improved overall survival by 20% in comparison with gemcitabine and cisplatin alone.

Nab-paclitaxel plus gemcitabine-Cisplatin may prolong survival versus cis-platinum-gemcitabine alone for the treatment of advanced biliary cancers.

Nivolumab has moderate efficacy.
Adjuvant Capecitabine for resected biliary tract cancers has some evidence of increased survival.

Leave a Reply

Your email address will not be published. Required fields are marked *