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INTRODUCTION

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For most patients, pancreatic adenocarcinoma remains highly lethal and is the fourth leading cause of deaths from cancer in the USA. Less than 5% survive 5 years after diagnosis. Surgical resection is the only curative treatment. However, the cure rate with surgery is only 18%–25% and most patients are not surgical candidates. Patients with unresectable disease can have symptoms palliated by chemotherapy and/or radiation therapy. However, these have not significantly impacted 5-year survival. Improved understanding of pancreatic cancer biology continues to provide new therapeutic ideas. Trials are evaluating whether new approaches to earlier diagnosis or improvements in radiation therapy, chemotherapy (including targeted therapy), and/or immunotherapy (e.g., vaccines, therapy aimed at inhibiting negative immunoregulatory proteins) can impact survival.

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INCIDENCE AND EPIDEMIOLOGY

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  • Approximately 45,000 individuals develop pancreatic cancer yearly in the United States with over 38,000 dying from the disease.

  • Increases with age, slight male predominance, increased incidence in African Americans, variation in prevalence by world region (higher in western Europe, Scandinavia, the United States, and New Zealand) (1).

  • Risk factors for pancreatic adenocarcinoma include (1,2,3):

    Environmental

    • Cigarette smoking, history of diabetes mellitus, previous radiation therapy to the pancreas as treatment for other malignancies (such as Hodgkin's disease, or testicular cancer) and chronic pancreatitis (especially that due to genetic risk factors); increased body mass index and heavy alcohol consumption (but not light consumption) may be risk factors.

      Genetic

    • Mutations in p16; mismatched repair genes (hMSH2 and hMLH1); BRCA1 (rare pancreatic cancers); BRCA2; PALB2 (a BRCA associated protein), STK11/LKB1 (Peutz-Jeghers syndrome); ataxia telangectasia (AT); p53 (Li-Fraumeni syndrome); APC (familial adenomatous polyposis); von Hippel-Lindau (VHL); cationic trypsinogen (PRSS1 gene); and cystic fibrosis transmembrane regulator (CFTR) genes (2,3,4).

  • Families with increased risk of pancreatic cancer without as yet defined genetic abnormalities.

  • Overall, approximately 5%–10% of patients with pancreatic cancer will have a first-degree relative who develops pancreatic cancer (2,3,4).

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PATHOLOGY

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Normal pancreatic cell types include ductal, acinar, endocrine/neuroendocrine, connective tissue support, endothelial, and lymphocytes. Malignancies can arise from each cell type. In adults, approximately 90% are adenocarcinomas derived from duct cells with approximately two-thirds arising in the head, and one-third being in the body/tail or multicentric (5,6,7). Other histologic subtypes of ductal origin include pleomorphic carcinomas, giant cell carcinomas, microglandular adenocarcinomas, and cystic neoplasms. Cystic neoplasms comprise a small but increasingly identified subgroup of pancreatic tumors (7). They can be divided into serous cyst adenomas (usually benign) and mucinous cystadenocarcinomas. A higher percentage of these tumors occur in middle-aged women as compared to ductal adenocarcinomas. They appear to be divided into a group that has benign or borderline malignant cells with good prognosis and a group with carcinoma that metastasizes widely and has a prognosis similar to that of other ductal adenocarcinomas. Pancreatic papillary cystic ...

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