ESSENTIALS OF DIAGNOSIS
Obstructive jaundice (may be painless).
Enlarged gallbladder (may be painful).
Upper abdominal pain with radiation to back, weight loss, and thrombophlebitis are usually late manifestations.
Carcinoma is the most common neoplasm of the pancreas. About 75% are in the head and 25% in the body and tail of the organ. Pancreatic carcinomas account for 2% of all cancers and 5% of cancer deaths. Ampullary carcinomas are much less common. Risk factors for pancreatic cancer include age, tobacco use (which is thought to cause 20–25% of cases), heavy alcohol use, obesity, chronic pancreatitis, diabetes mellitus, prior abdominal radiation, family history, and possibly gastric ulcer and exposure to arsenic and cadmium. New-onset diabetes mellitus after age 45 years occasionally heralds the onset of pancreatic cancer. In diabetic patients, metformin use and possibly aspirin use may reduce the risk of pancreatic cancer slightly, but insulin use and glucagon-like peptide-1–based therapy (eg, sitagliptin) may increase the risk. A risk model for pancreatic cancer in persons with new-onset diabetes mellitus has been proposed and includes the following factors: age, body mass index, change in body mass index, smoking, use of proton pump inhibitors and diabetes medications as well as levels of hemoglobin A1C, cholesterol, hemoglobin, creatinine, and alkaline phosphatase. About 7% of patients with pancreatic cancer have a family history of pancreatic cancer in a first-degree relative, compared with 0.6% of control subjects. Point mutations in codon 12 of the K-ras oncogene are found in 70–100% of pancreatic cancers; inactivation of the tumor suppressor genes CDKN2A on chromosome 9, TP53 on chromosome 17, and SMAD4 on chromosome 18 is found in 95%, 75%, and 55% of pancreatic cancers, respectively; mutation of the palladin gene (PALLD) is reported to be common. The majority of pancreatic cancers originate from pancreatic intraepithelial neoplasias, which measure less than 5 mm in diameter and can only be seen with a microscope.
In 5–10% of cases, pancreatic cancer occurs as part of a hereditary syndrome, including familial breast cancer (carriers of BRCA2 have a 7% lifetime risk of pancreatic cancer), hereditary pancreatitis (PSS1 mutation), familial atypical multiple mole melanoma (p16/CDKN2A mutation), Peutz-Jeghers syndrome (STK11/LKB1 mutation), ataxia-telangiectasia (ATM mutation), and Lynch syndrome (hereditary nonpolyposis colorectal cancer [MLH1, MSH2, MSH6 mutations]). Polymorphisms of the genes for methylene tetrahydrofolate reductase and thymidylate synthase have been reported to be associated with pancreatic cancer.
Neuroendocrine tumors account for 1–2% of pancreatic neoplasms and may be functional (producing gastrin, insulin, glucagon, vasoactive intestinal peptide, somatostatin, growth hormone–releasing hormone, adrenocorticotropic hormone, and others) or nonfunctional. Cystic neoplasms account for only 1% of pancreatic cancers, but they are important because pancreatic cysts are common and may be mistaken for pseudocysts. A cystic neoplasm should be suspected when a cystic lesion in the pancreas is found in the absence of a history of ...