Invited Lecture(JSGE)
Sat. November 7th   9:00 - 9:30   Room 3: Kobe International Exhibition Hall No.2 Building Conference Room 3A
Invited Lecture3
 Inflammation and carcinogenesis (biliary and pancreas)
David C. Whitcomb
University of Pittsburgh
Cancer is a disease of acquired somatic mutations that irreversibly alter the biology of normal cells to make them proliferate and metastasize with progressive aversion to control mechanisms. The process requires that multiple pathogenic genetic mutations develop within an initial cancer cell that then produces progressively degenerate daughter cells. With this conceptual background we now ask why specific cancers develop in individual patients - why the pancreas or the biliary system?

Pancreatic cancer (pancreatic ductal adenocarcinoma, PDAC) is a disease of the elderly with an average age of about 70 years. Much effort has been directed to searching for inherited gene mutations that cause pancreatic cancer, but most cases appear sporadic and the few familial cases reveal genes associated with multiple cancers due to defective DNA repair or cell cycle controls - relevant to all cells. Epidemiology studies point to smoking and chronic pancreatitis as the highest risk factors, and these factors are highlighted by studies in hereditary pancreatitis.

Biliary cancer (cholangiocarcinoma) can occur within the liver, within the hilum or distal to the liver in the bile duct, including intrapancreatic locations. Biliary cancers differ from pancreatic cancer in demographics (higher in Hispanic and Asian ancestry, lowest in African ancestry) and in somatic mutation profiles. However, like PDAC, chronic inflammation is the primary risk factor. Examples include parasites (e.g. liver flukes Opisthorchis viverrini or Clonorchis sinensis), bile duct stones, environmental factors and inflammatory diseases, especially primary sclerosing cholangitis.

Both PDAC and biliary cancers arise from duct cells that arise from the same developmental evagination of the developing foregut and they share multiple features. The process of oncogenesis also shares key genetic features and immune defense responses, including generation of dense fibrosis. Each of these pathologic features are driven by, or linked to the underlying genetic variants that define the development and survival of pancreatic and biliary cancers.
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