Pancreatic Cancer : From Clinical to Molecular Aspects

Abstract

Pancreatic ductal adenocarcinoma usually has a very poor outcome. The majority of patients present late with locally advanced or metastatic disease, and only 10-20% are candidates for resection. The tumor marker CA19-9 may be elevated but is not specific for pancreatic cancer. Dual-phase spiral computed tomography is the most important imaging modality for the diagnosis of pancreatic cancer. Despite the continuing development of body imaging methods and serum determination of tumor markers, the diagnosis of pancreatic carcinoma often remains problematic. Endoscopic retrograde cholangiopancreatography is considered to be one of the most reliable diagnostic procedures for pancreaticobiliary diseases. Endoscopic ultrasonography has been developed as an intracorporeal imaging method that now provides precise ultrasonic images of the pancreas. Pancreaticoduodenectomy is the mainstay of surgical treatment which offers the only hope of cure for this disease. Biliary-enteric and gastrojejunal bypass used to be the standard operation for inoperable pancreatic cancer. Endoscopic stenting can produce good palliation of biliary obstruction. The median survival after resection is only 18-20 months and up to 50% of those who survive 5 years may die of recurrent cancer. The factors that predict recurrence and survival are the resection margin, the size of the tumor, lymph node involvement and histological appearance of the degree of differentiation of the cancer tissue.
     Pancreatic cancer is a consequence of stepwise accumulated genetic alterations which disturb the equilibrium of a cell by altering the relative balance between the roles of the cell cycle, differentiation and dedifferentiation, and programmed cell death (apoptosis). Multiple genetic alterations involving the activation of oncogenes (K-ras) and inactivation of tumor suppressor genes (p53, p16 and DPC4) and telomerase. The detection of early tumor, i.e., the establishment of a screening strategy, the development of adjuvant therapy and molecular approaches might provide more options and a better clinical outcome for pancreatic cancer.