Porth's Essentials of Pathophysiology, 4e

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Gastrointestinal and Hepatobiliary Function

U N I T 8

extent that endocrine and exocrine pancreatic functions become deficient. At this point, signs of diabetes mellitus and the malabsorption syndrome (e.g., weight loss, fatty stools [steatorrhea]) become apparent. Treatment consists of measures to treat coexist- ing biliary tract disease. A low-fat diet usually is pre- scribed. The signs of malabsorption may be treated with pancreatic enzymes. When diabetes is present, it is treated with insulin. Alcohol is forbidden because it frequently precipitates attacks. Because of the fre- quent episodes of pain, narcotic addiction is a potential problem in persons with chronic pancreatitis. Surgical intervention sometimes is needed to relieve the pain and usually focuses on relieving any obstruction that may be present. Cancer of the Pancreas Pancreatic cancer is now the fourth leading cause of death from cancer in the United States, preceded only by lung, colon, and breast cancer. 47,48 Considered to be one of the most deadly malignancies, pancreatic cancer is associated with a 5-year survival rate of only 4% to 6%. 47,48,54,55 The incidence of pancreatic cancer seems to be increasing in all countries studied and has tripled in the United States over the past 50 years. 48 The cause of pancreatic cancer is unknown. Age is a major risk factor. Pancreatic cancer rarely occurs in per- sons younger than 50 years of age, and the risk increases with age. The most significant and reproducible environ- mental risk factor is cigarette smoking, which doubles the risk. 47,48,54–56 Diabetes and chronic pancreatitis also are associated with pancreatic cancer, although neither the nature nor the sequence of the possible cause-and- effect relation has been established. There has been a recent focus on the molecular genetics of pancreatic cancer. Clinical Manifestations. Almost all pancreatic can- cers are adenocarcinomas of the ductal epithelium, and symptoms are primarily caused by mass effect rather than disruption of exocrine or endocrine function. The clinical manifestations depend on the size and location of the tumor as well as its metastasis. 54–56 Pain, jaundice, and weight loss constitute the classic presentation of the disease. The most common pain is a dull epigastric pain often accompanied by back pain, often worse in the supine position, and relieved by sitting forward. Patients may also present with diabetes or impaired glucose tol- erance. Because of the proximity of the pancreas to the common duct and the hepatopancreatic ampulla, cancer of the head of the pancreas tends to obstruct bile flow. Jaundice frequently is the presenting symptom of a per- son with cancer of the head of the pancreas, and it usu- ally is accompanied by complaints of pain and pruritus. Cancer of the body of the pancreas usually impinges on the celiac ganglion, causing pain. The pain usually wors- ens with ingestion of food or assumption of the supine position. Cancer of the tail of the pancreas usually has metastasized before symptoms appear. Migratory thrombophlebitis (deep vein thrombo- sis) develops in about 10% of persons with pancreatic

cancer, particularly when the tumor involves the body or tail of the pancreas. Thrombi develop in multiple veins, including the deep veins of the legs, the subcla- vian vein, the inferior and superior mesentery veins, and even the vena cava. It is not uncommon for the migratory thrombophlebitis to provide the first evi- dence of pancreatic cancer, although it may present in other cancers as well. The mechanism responsible for the hypercoagulable state is largely unclear, but may relate to activation of clotting factors by proteases released from the tumor cells. 48 Diagnosis and Treatment. Patient history, physical examination, and elevated serum bilirubin and alka- line phosphate levels may suggest the presence of pan- creatic cancer but are not diagnostic. 54–56 The serum cancer antigen (CA) 19–9, a Lewis blood group anti- gen, may help confirm the diagnosis in symptomatic patients and may help predict prognosis and recurrence after resection. However, CA 19–9 lacks the sensitiv- ity and specificity to effectively screen asymptomatic patients. 56 Ultrasonography and CT scanning are the most frequently used diagnostic methods to confirm the disease. Intravenous and oral contrast–enhanced spiral CT is the preferred method for imaging the pan- creas. Percutaneous fine needle aspiration cytology of the pancreas has been one of the major advances in the diagnosis of pancreatic cancer. Unfortunately, the smaller and more curable tumors are most likely to be missed by this procedure. Endoscopic retrograde chol- angiopancreatography may be used for evaluation of persons with suspected pancreatic cancer and obstruc- tive jaundice. Most cancers of the pancreas have metastasized at the time of diagnosis. Surgical resection of the tumor is done when the tumor is localized or as a palliative mea- sure. Radiation therapy may be useful when the disease is localized but not resectable. The use of irradiation and chemotherapy for pancreatic cancer continues to be investigated. Pain control is one of the most important aspects in the management of persons with end-stage pancreatic cancer.

SUMMARY CONCEPTS

■■ The biliary tract, which consists of the bile ducts and gallbladder, serves as a passageway for the delivery of bile from the liver to the intestine. ■■ The most common causes of biliary tract disease are cholelithiasis and cholecystitis.Three factors contribute to the development of cholelithiasis: abnormalities in the composition of bile, stasis of bile, and inflammation of the gallbladder. Cholelithiasis, in turn, predisposes to obstruction of bile flow, causing biliary colic and acute or chronic cholecystitis.