pancreatic cancer

Malignant tumour of the pancreas.

Risk factors include smoking, a diet high in fat, exposure to certain industrial products, and diseases such as diabetes and chronic pancreatitis. Pancreatic cancer is more common in men. Symptoms often do not appear until pancreatic cancer is advanced; they include abdominal pain, unexplained weight loss, and difficulty digesting fatty foods. Surgery, radiation therapy, chemotherapy, or some combination of these may be used to treat the disease.

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▪ pathology

Introduction

      a disease characterized by abnormal growth of cells in the pancreas, a 15-cm- (6-inch-) long gland located behind the stomach. The pancreas 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 (endocrine system, human) pancreas, which secretes glucagon and insulin into the bloodstream to control blood sugar levels. Ninety-five percent of pancreatic cancers develop from the exocrine pancreas. The remaining 5 percent are often called neuroendocrine tumours 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. Symptoms often do not appear until the cancer has advanced to a late stage; they include abdominal pain, unexplained weight loss, problems with sugar metabolism, and difficulty digesting fatty foods. As a pancreatic tumour 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 tumours, and central obesity (accumulation of fat primarily around the abdomen), which can increase 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. Furthermore, 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. Uncontrollable risk factors include age, sex—males are 30 percent 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, generally defined as the occurrence of pancreatic cancer in at least one pair of first-degree relatives. Mutations in a gene designated PALLD (palladin, or cytoskeletal associated protein) have been linked to familial pancreatic cancer.

Diagnosis and prognosis

      Blood tests that assess various pancreatic and liver functions may suggest pancreatic cancer. If cancer is suspected, a needle biopsy or an endoscopy procedure is usually conducted to examine pancreatic cells or the pancreas itself for signs of cancer. However, these procedures are invasive and are associated with an increased risk for serious complications, including pancreatitis. In order to make a correct diagnosis and to determine the stage of the cancer, multiple imaging (diagnostic imaging) techniques may be employed that allow doctors to see the pancreas, despite its location deep within the abdominal cavity. Imaging techniques commonly used include computed tomography (computerized axial tomography) (CT) scans, magnetic resonance imaging (diagnosis) (MRI), and different types of ultrasound (diagnosis), including transabdominal ultrasound (imaging performed on the external surface of the abdomen) and endoscopic ultrasound (EUS; an ultrasound device is sent through an endoscope to take images of internal tissues). Various techniques that combine contrast agents (dyes) with X-ray imaging are also used to determine whether the bile duct or other ducts within the pancreas are blocked. One example is called percutaneous transhepatic cholangiography (PTC), in which a needle is used to inject a dye directly into the liver, followed by X-ray imaging. Other X-ray imaging techniques include angiography, in which X-rays are used to view blood vessels to determine if the cancer has spread through the walls of the vessels feeding into the pancreas.

      Because early detection of pancreatic cancer is critical for patient survival, research is becoming increasingly focused on specific markers (subtle, identifiable cellular changes) that are detectable in precancerous pancreatic lesions. One method of early detection employs special light-scattering spectroscopy techniques in combination with existing endoscope technology. This light-scattering imaging technology is extremely sensitive and is aimed at detecting specific markers in cells in the first part of the small intestine (the duodenum) that are indicative of very early precancerous pancreatic lesions. It is also much less invasive than needle biopsy and traditional endoscopy procedures for pancreatic lesion detection because doctors need only examine an easily accessible region in the small intestine.

      Once pancreatic cancer has been diagnosed, its stage is then determined to indicate how far the cancer has progressed. Stage I cancers are confined to the pancreas and have not spread to nearby lymph nodes. Stage II cancers have spread locally to the bile duct or small intestine but have not reached the lymph nodes, whereas stage III tumours have reached these nodes. Stage IV cancers have spread to other organs such as the lungs, liver, spleen, or colon.

      The survival rate from pancreatic cancer is lower than that seen with many other cancers because the symptoms of pancreatic cancer often do not become obvious until the later stages of the disease. The average five-year survival rate from all stages of pancreatic cancer is extremely low, as is the one-year survival rate. However, survival rates are higher for patients who have their cancer diagnosed early in the course of the disease.

Treatment (therapeutics)

       surgery can be used to treat pancreatic cancer, but, given the poor prognosis of the disease and the unusually high number of complications associated with pancreatic surgery, surgery is usually reserved for cases in which there is a reasonable possibility of curing the disease. If the cancer is considered to be incurable, major surgery is done mainly to relieve symptoms or digestive problems. Islet cell tumours are often localized to the tail of the pancreas, and a distal pancreatectomy may be conducted to remove this portion of the pancreas along with the spleen.

      Exocrine cancers are often treated with the Whipple procedure, a complicated surgical approach that removes all or part of the pancreas and nearby lymph nodes, the gallbladder, and portions of the stomach, small intestine, and bile duct. Serious complications often arise following this procedure, which requires an extensive hospital stay and considerable experience on the part of the surgeon. Other exocrine tumours are sometimes treated by complete removal of the pancreas (total pancreatectomy). Surgery can also be used to relieve complications of pancreatic cancers, such as obstruction of the bile duct. The bile duct may be redirected around the tumour, or a tube may be placed in the bile duct to keep it open.

       radiation therapy is sometimes used in conjunction with surgery—often prior to surgery to reduce a tumour to a more manageable size but also after surgery to destroy any remaining cancer cells. The position of the pancreas in the abdominal cavity makes it a difficult target for focused radiotherapy, but a procedure using radiotherapy simultaneously with surgery permits the surgeon to focus radiation directly onto the pancreas by moving obstructing organs aside. Side effects of this radiation therapy may include vomiting, diarrhea, fatigue, or skin irritations resembling a sunburn.

      Chemotherapy is generally used when pancreatic cancers have spread to distant organs and may be required so that as many cancer cells as possible can be sought out and destroyed. Endocrine or islet cell tumours may be treated with hormone therapy, in which specific hormones are used to stop or slow the growth of the cancer in the endocrine cells. Targeted drug therapies that block cellular processes driving cancer cell proliferation have been used in combination with chemotherapy in some pancreatic cancer patients. For example, a drug called erlotinib (Tarceva) blocks the activity of a kinase (a type of enzyme) associated with the epidermal growth factor receptor (EGFR), which stimulates unregulated cell division when mutated in cancer cells. When erlotinib is given in combination with the chemotherapeutic agent gemcitabine (Gemzar), an antimetabolite that inhibits the synthesis of genetic material in dividing cells, patient survival is improved, although only modestly. Several other targeted drugs such as cetuximab (Erbitux), a monoclonal antibody that binds to EGFR and thus prevents kinase activation and cell division, are being developed and tested in clinical trials for pancreatic cancer.

Prevention

      In most cases, pancreatic cancer cannot be completely prevented, but risk can be decreased by reducing or eliminating cigarette smoking and following a diet low in animal products and high in fruits and vegetables. Researchers are also investigating anti-inflammatory therapeutic agents that inhibit an enzyme called cyclooxygenase-2 (COX-2). Because COX-2 plays a role in inflammation and mediates tumour growth and development, it is a valuable target for the development of drugs used in the prevention and treatment of several cancers, including breast cancer, colorectal cancer, and pancreatic cancer. In people at risk for familial pancreatic cancer, routine endoscopy can be used to monitor changes in pancreatic tissue. If tissue abnormalities arise, the pancreas can be removed before cancer develops.

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