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Cholangiocarcinoma: preventing invasion as anti-cancer strategy.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Gores, Gregory J. |
| Copyright Year | 2003 |
| Abstract | Cholangiocarcinomas are adenocarcinomas arising from cholangiocytes, the epithelial cells lining the bile duct apparatus. Because the biliary tree is both intraand extrahepatic, cholangiocarcinomas likewise may arise within the liver parenchyma or from the extrahepatic bile ducts. Cholangiocarcinomas arising within the hepatic parenchyma often present as intrahepatic mass lesions whereas cancers developing along the extrahepatic ducts cause mechanical biliary obstruction with jaundice, pruritus, acholic stools, and weight loss. For reasons unexplained, the extrahepatic ductal cholangiocarcinomas frequently involve the hilum of the liver, the junction of the right and left hepatic ducts. These perihilar ductal cholangiocarcinomas, therefore, frequently present with biliary obstruction of one or both lobes of the liver. Several epidemiologic studies have now demonstrated an increase in the incidence of cholangiocarcinoma in Western countries [1–4]. Because the incidence of cholangiocarcinoma is increasing, most hepatologists now frequently encounter this disease. Many patients with cholangiocarcinoma do not have identified risk factors for this disease. However, established risk factors include primary sclerosing cholangitis, biliary-enteric drainage procedures associated with cholangitis, Caroli’s disease, congenital choledochal cysts, chronic hepatic lithiasis, and liver fluke infestations (Clonorchis sinsesis and Opithorchis viverrini infections) [5]. In primary sclerosing cholangitis the risk of developing cholangiocarcinoma is approximately 0.5–1.5% per year [6]. The common link between these risk factors and cholangiocarcinoma is chronic inflammation. Like other organs in the gastrointestinal tract, chronic inflammation of the biliary tree predisposes to carcinogenesis. Chronic inflammation is associated with inflammatory cytokines which serve as cholangiocyte mitogens (interleukin6), nitrosative and oxidative stress causing DNA damage, and the induction of tumor promoting proteins (i.e. cyclooxygenase-2) [7–10]. These concomitant processes likely promote initiation, promotion and progression of these neoplasms. Therapy for cholangiocarcinoma is limited. Surgical extirpation is thought to be the treatment of choice, but resection for cure is often not feasible due to: (i) anatomic location of the cancer (spread to the secondary bifurcations of both the right and left hepatic ducts or involvement of the contralateral lobar vessels with ipsilateral extension into the secondary duct bifurcations of the primarily affected lobe); and/or (ii) the presence of extraor intrahepatic metastases [11,12]. Furthermore, death due to recurrent disease occurs in the majority of patients thought to be resected for cure (i.e. disease-free margins). Liver transplantation leads to excellent long-term disease-free survival in highly selected patients receiving preoperative chemoirradiation therapy [13–15]. However, most patients present with advanced disease and are not eligible for this therapeutic modality. For these patients, relief of biliary obstruction via mechanical or plastic biliary stents with or without photodynamic therapy constitute the only palliative options [5]. A recent consensus conference on this disease concluded that there are no data supporting a survival advantage for patients receiving radiation and/or cytotoxic chemotherapy [5]. Thus, therapeutic options are limited for many cholangiocarcinoma patients. Further, advances in the therapy of cholangiocarcinoma will most likely be predicated on a molecular understanding of this disease. Advanced cancers are like military institutions manifesting growth, possessing strong defense mechanisms (e.g. avoidance of apoptosis), and having the ability to attack, e.g., processes authorizing tissue invasion and metastasis. To accomplish these cellular alterations molecular events activating oncogenes, inactivating tumor suppressor genes, blocking DNA repair processes, and inducing limitless replication for survival must occur. Recent advances have demonstrated that cholangiocarcinomas frequently express COX-2 (an enzyme involved in prostanoid metabolism), and c-erB-2 and c-met, receptor tyrosine kinases [16]. Journal of Hepatology 38 (2003) 671–673 |
| Starting Page | 426 |
| Ending Page | 426 |
| Page Count | 1 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.panaceaglobalinc.com/edit/files/pdfs/publications/8-gores-editorial-jrl-of-hepatology.pdf |
| PubMed reference number | 12713880v1 |
| Volume Number | 38 |
| Issue Number | 5 |
| Journal | Journal of hepatology |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Adenocarcinoma Anatomic Site Apoptosis Bile Ducts, Extrahepatic Bile duct structure Biliary Tract Diseases Biliary tract obstruction Biliary tract structure Blood Vessel Carcinogenesis Cessation of life Cholangiocarcinoma Cholangitis, Sclerosing Choledochal Cyst Chronic inflammation Clonorchiasis Cultured Cell Line Cytotoxic Chemotherapy DNA Repair Defense Mechanisms Diarrhea Duct (organ) structure Epidemiology Excision Fasciola hepatica Feces Fungal eye infections Gastrointestinal tract structure Genes, Suppressor Hepatic Duct How Much Distress Weight Loss Icterus Lithiasis Liver neoplasms Liver parenchyma MET wt Allele Mitogens Noninfiltrating Intraductal Carcinoma Oncogenes Organ Oxidative Stress Patients Photochemotherapy Primary sclerosing cholangitis Promotion (action) Prostaglandins Pruritus Receptor Protein-Tyrosine Kinases Recurrent disease Stent, device Trematoda Tumor Suppressor Genes Tyrosine advanced cancer chronic liver disease cyclooxygenase 2 lobe prostanoid metabolic process |
| Content Type | Text |
| Resource Type | Article |
