pancreatic cancer

pancreatic cancer, a disease characterized by abnormal growth of cells in the pancreas, a gland located behind the stomach. The pancreas, which has an elongated (15-cm- [6-inch-] long), tapering structure, is primarily made up of two different tissues with separate functions: the exocrine pancreas, which secretes enzymes into the digestive tract, aiding the breakdown of fats and proteins, and the endocrine pancreas, which secretes glucagon and insulin into the bloodstream in order to control blood sugar levels. Approximately 95 percent of pancreatic cancers develop from the exocrine pancreas. The remaining 5 percent are often referred to as neuroendocrine tumors or islet-cell cancers; these develop from endocrine cells.

Symptoms and causes

As is the case with many cancers, symptoms of pancreatic cancer are shared with those of many other illnesses and often do not appear until the cancer has advanced to a late stage. Symptoms typically include abdominal pain, unexplained weight loss, problems with sugar metabolism, and difficulty digesting fatty foods. As a pancreatic tumor grows, it may block the common bile duct, which leads to a buildup of bilirubin in the blood and causes jaundice (a yellowing of the skin and eyes). Blockage of the bile duct may also cause the gallbladder to become enlarged.

The causes of pancreatic cancer vary and in many cases remain unknown. However, several factors have been identified that increase the risk of developing pancreatic cancer. The two most important of these factors are smoking, which is associated with about 30 percent of pancreatic tumors, and central obesity (accumulation of fat primarily around the abdomen), which can increase the risk of pancreatic cancer by as much as 70 percent in some postmenopausal women. In both men and women, central obesity is associated with increased levels of insulin and with disruption of normal endocrine and metabolic functions. However, the mechanism by which abnormally high insulin levels and dysfunctional metabolism in centrally obese individuals give rise to pancreatic cancer is unclear. A diet high in animal products, particularly animal fat, also increases cancer risk. Environmental factors, such as exposure to certain dyes, pesticides, and petroleum products, may increase the probability of developing pancreatic cancer as well.

Uncontrollable risk factors include age, sex—males are slightly more likely to develop cancers of the pancreas than are females—and illnesses such as diabetes mellitus and chronic pancreatitis. An estimated 10 percent of cases of pancreatic cancer are the result of inherited defects. Some of these cases arise in association with known genetic syndromes, such as Peutz-Jeghers syndrome and hereditary nonpolyposis colon cancer, whereas others are associated with familial pancreatic cancer, which is generally defined as the occurrence of pancreatic cancer in at least one pair of first-degree relatives. Mutations in several different genes have been linked to familial pancreatic cancer, including mutations in BRCA1, BRCA2, CDKN2A, TP53, and PALLD; some of these genes are strongly linked to an increased risk of other cancer types, including melanoma and cancers of the breast, ovaries, and prostate.

Islet-cell tumors

Tumors of the endocrine pancreas, which occur in the cells of the islets of Langerhans, are rare and are often classified as functional or nonfunctional tumors. Functional tumors are characterized by excess hormone secretion, whereas nonfunctional tumors, which are more common, do not secrete hormones. The most common functional tumor of the endocrine pancreas is an insulin-secreting tumor called an insulinoma, which is benign in about 90 percent of affected patients. In some cases, hypersecretion of insulin may be caused by diffuse hyperplasia (abnormal increase in cell number) of the islet cells or by a carcinoma (malignant tumor) of the islet cells. A small number of patients with hypersecretion of insulin have islet-cell hyperplasia or single or multiple insulin-secreting tumors (insulinomas) as part of a syndrome known as multiple endocrine neoplasia type 1 (MEN1; characterized primarily by islet, parathyroid, and pituitary tumors). In addition, diffuse hyperplasia of beta cells, called nesidioblastosis, can cause hypoglycemia (abnormally low blood glucose levels) in infants.

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A type of malignant tumor of the endocrine pancreas is gastringastrinoma, a type of gastrin-secreting tumor. The gastrin stimulates the stomach to produce acid, and therefore ulcers of the stomach and duodenum are common. This disorder is known as Zollinger-Ellison syndrome. Gastrinomas may also originate in the stomach and duodenum. Gastrinomas are associated with MEN1 in some patients. A very rare type of tumor of the endocrine pancreas is glucagonoma, a glucagon-secreting tumor. Glucagonomas cause a “diabetes-dermatitis syndrome” that is characterized by mild diabetes, anemia, and a red blistering rash that appears in one area of the body and then fades, only to reappear at a different site. These patients have very high serum glucagon concentrations but only mild type II diabetes. Other rare tumors of the islet cells include somatostatin-secreting tumors (somatostatinomas) and pancreatic polypeptide-secreting tumors.

Tumors of the endocrine pancreas are difficult to diagnose because findings are nonspecific and may include diabetes, gallstones, excessive fat in the stool, indigestion, and diminished secretion of gastric acid. In addition, islet-cell tumors may also produce “ectopic” hormones, meaning that the tumor secretes a hormone that is not normally secreted by the tissue in which the tumor occurs.

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