Cholangiocarcinoma

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Abstract

Cholangiocarcinoma is an uncommon adenocarcinoma with poor prognosis. Although the 1-year survival has increased over time, the 5-year survival has not shown any significant change (less than 5%). Cure can only be expected from surgical resection of early stage tumours but most patients initially present with advanced disease. Cancer cachexia, liver failure, and recurrent sepsis due to biliary obstruction are among the main causes of mortality.

Patients’ prognosis is strongly related to radical surgery and complete resection is the most effective therapy; the location within the biliary tree (proximal versus distal) has no impact on survival when a complete resection is achieved despite the fact the rate of resectability is up to 70% in case of distal cancer and 15–20% for high bile ducts tumours. Prognosis of cholangiocarcinoma remains poor even with aggressive surgical therapy because of the high incidence of local or regional recurrence and distant metastasis.

Based on these data many questions need an answer: is there a role for adjuvant chemotherapy or radiotherapy? Neoadjuvant treatments provide best results? There is a standard therapy in unresectable or metastatic cholangiocarcinoma?

This report tries to answer to frequently asked questions that the readers are faced with their patients every day (from diagnostic procedures to palliative treatment) and tries to suggest useful information for their professional practice.

Section snippets

Incidence

Cholangiocarcinoma is an uncommon adenocarcinoma which arises from the epithelial cells of bile ducts, anywhere along intrahepatic and extrahepatic biliary tree, excluding the papilla of Vater and the gall bladder. In Europe, approximately 50,000 new cases of primary liver cancer are diagnosed every year [1]. Data from the Cancer Incidence in Five Continents initiative [1], [2], indicate that approximately 20% of those cases are attributed to cholangiocarcinoma. The annual age-standardised

Molecular data

The development of cholangiocarcinoma is a multistep process based on enhanced susceptibility to proliferative stimuli and escape from growth inhibitory stimuli, dysregulation of apoptotic signals, and the response to angiogenetic stimuli which are eventually responsible for tumour invasion and metastasis [9], [19]. Several mutations in oncogenes and tumour-suppressor genes have been identified in cholangiocellular cancer. Their sequential occurrence is thought to drive the pathogenesis of

Signs and symptoms

The clinical signs and symptoms depend on the location of the tumour. Jaundice without pain is a leading symptom (>90% of patients) in extrahepatic bile duct cancer, while it is less frequent in patients with intrahepatic cholangiocarcinoma. Other clinical features common in biliary obstruction are pale stools, dark urine, and pruritus; further physical signs are hepatomegaly, right upper abdominal mass, weight loss, and fever. Patients presenting the triad cholestasis, abdominal pain and

Staging procedures

There is no system that stratifies patients into subgroups for potential resectability and simultaneously correlates with survival.

For extrahepatic cholangiocarcinoma (hilar and distal cholangiocarcinoma) there are two systems for staging, the American Joint Committee on Cancer (AJCC) TNM (tumour, node, metastases) Staging System (Table 4) and the modified Bismuth–Corlette classification (Table 1). Intrahepatic cholangiocarcinomas are classified as hepatocarcinoma (Table 5).

Prognostic factors

Prognosis is not influenced by the location of the cancer if radical surgery is performed (no difference in survival between various bile duct cancers when adjusted for stage and completeness of resection [37]. After surgical resection of intrahepatic cholangiocarcinomas, 5-year survival rates vary from 8% to 47%. The best prognosis has been observed in patients with negative resection margins [38]. For distal cholangiocarcinomas, 5-year survival rates of 20–54% have been reported. In a review

Surgery

Surgery is the only therapeutic option with a chance of cure. Surgery with curative intent must guarantee the complete excision of the tumour with negative margins. Potentially curative resection may include aggressive surgery (partial hepatectomy). Prognosis is strongly related to radical surgery and complete resection is the most effective therapy; the location within the biliary tree (proximal versus distal) has no impact on survival when a complete resection is achieved [37] despite the

Late sequelae

After surgery, complications consist of wound infections, sepsis, fistulae, cholangitis and, in cases of pancreaticoduodenectomy, delayed gastric empting [23]. Hilar cholangiocarcinoma requires an aggressive resection (partial hepatectomy), but the risk is the development of postoperative liver remnant dysfunction or failure (encephalopathy, ascites, coagulopathy). This risk can be reduced with preoperative portal vein embolization. Decompression of the biliary system can require percutaneous

Follow-up

There are no standard guidelines for surveillance after surgery. The role of the tumour marker, CA 19–9, has not been established, although a persistently rising level is suspected to be an indicator of recurrence, often appearing several months earlier than radiological evidence. Based on the lack of clinical trials a rational postoperative surveillance should include a physical examination and laboratory tests every 3 or 4 months for the first 3 years after surgery, then every 6 months until

Stefania Mosconi graduated in medicine at University of Milan in 2000, she specialized in Medical Oncology Unit at University of Pavia in 2006. Since 2000 she has shown a particular interest for gastrointestinal cancer and she is a member of GIOG (Gruppo Interdisciplinare di Oncologia Gastroenterologica), of Medical Oncology Unit at Ospedali Riuniti, Bergamo, Italy.

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  • Cited by (0)

    Stefania Mosconi graduated in medicine at University of Milan in 2000, she specialized in Medical Oncology Unit at University of Pavia in 2006. Since 2000 she has shown a particular interest for gastrointestinal cancer and she is a member of GIOG (Gruppo Interdisciplinare di Oncologia Gastroenterologica), of Medical Oncology Unit at Ospedali Riuniti, Bergamo, Italy.

    Giordano Domenico Beretta is Director of Medical Oncology Unit at Sant’Orsola-Fatebenefratelli Hospital, Brescia, Italy. He is co-ordinator of Colorectal Guidelines Task Force of AIOM (Italian Association of Medical Oncology) since 2002.

    Roberto Labianca is Director of Department of Oncology-Hematology at Ospedali Riuniti, Bergamo, Italy. He is scientific secretary of GISCAD (Italian Group for the Study of Gastrointestinal Cancer) and President of AIOM (Italian Association of Medical Oncology) for the years 2003–2005.

    Maria Giulia Zampino is Deputy-Director of Medical Care Unit, European Institute of Oncology, Milan, Italy specifically involved in gastrointestinal clinical and scientific projects.

    Gemma Gatta is Director of the Evaluative Epidemiology Unit, Department of Preventive and Predictive Medicine, National Cancer Institute, Milan, Italy.

    Volker Heinemann is medical doctor at the Department of Hematology/Oncology, Klinikum Grosshadern, University of Munich and professor of Medical Oncology at the University of Munich, Germany.

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