Chapter 089. Pancreatic Cancer (Part 1)

Harrisons Internal Medicine Chapter 89. Pancreatic CancerPancreatic Cancer: IntroductionOver 90% of pancreatic cancers are ductal adenocarcinomas of the exocrine pancreas. These tumors occur twice as frequently in the pancreatic head compared to the rest of the organ, and tend to be aggressive, often presenting when locally inoperable or after distal metastases have occurred. Patients with pancreatic cancer have a poor prognosis, with a 5-year survival of only 5%. The discussion of pancreatic cancer here will be limited to ductal adenocarcinomas. Other types of pancreatic neoplasms include islet cell tumors and neuroendocrine tumors (Chap. 344).Incidence and EtiologyEpidemiologyThe lifetime risk...
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Chapter 089. Pancreatic Cancer (Part 1) Chapter 089. Pancreatic Cancer (Part 1) Harrisons Internal Medicine > Chapter 89. Pancreatic Cancer Pancreatic Cancer: Introduction Over 90% of pancreatic cancers are ductal adenocarcinomas of the exocrinepancreas. These tumors occur twice as frequently in the pancreatic head comparedto the rest of the organ, and tend to be aggressive, often presenting when locallyinoperable or after distal metastases have occurred. Patients with pancreatic cancerhave a poor prognosis, with a 5-year survival of only 5%. The discussion ofpancreatic cancer here will be limited to ductal adenocarcinomas. Other types ofpancreatic neoplasms include islet cell tumors and neuroendocrine tumors (Chap.344). Incidence and Etiology Epidemiology The lifetime risk of being diagnosed with pancreatic cancer in the UnitedStates is 1.27%. In the United States, it is estimated that approximately 37,170people will be diagnosed with pancreatic cancer in 2007. Consistent with itsassociated poor prognosis, 33,370 are expected to die from this disease in the sameyear, making it the fourth leading cause of cancer-related death. The median ageof diagnosis of pancreatic cancer is 72 years, with the peak incidence of diagnosisbetween the ages of 65 and 84; it is rarely diagnosed in those below the age of 50.The incidence is slightly higher in men than women, and it is also higher inAfrican Americans than in Caucasians. Etiology Cigarette smoking, obesity, and nonhereditary chronic pancreatitis appearto be risk factors for the development of pancreatic cancer. With smoking, the riskseems to increase with the number of cigarettes consumed and decreases withsmoking cessation. Less clear, and sometimes conflicting associations, have beenobserved for other environmental factors such as diet, coffee and alcoholconsumption, previous partial gastrectomy or cholecystectomy, and Helicobacterpylori. An epidemiologic association between diabetes mellitus and pancreaticcancer has also been demonstrated; however, it is uncertain if diabetes is aprecedent of, or consequence of, pancreatic cancer. Genetic Considerations Five to 10% of patients with pancreatic cancer also have an affected first-degree relative, suggesting that in some cases genetic factors are involved. Thesepatients seem to present earlier than sporadic cases. The risk of pancreatic canceris increased in certain syndromes, whether directly or indirectly, such as hereditarychronic pancreatitis, Peutz-Jeghers syndrome, Von Hippel-Lindau syndrome,familial atypical multiple-mole melanoma syndrome, ataxia-telangiectasia,Gardners syndrome [a variant of familial adenomatous polyposis (FAP)] andLynch syndrome II, a subtype of hereditary nonpolyposis colorectal cancer(HNPCC). Heavy smokers who also have homozygous deletions of the gene forglutathione-S transferase T1 (GSTT1), a carcinogen metabolizing enzyme, may beat particular risk. Activating mutations in the K-ras oncogene are found in nearlyall pancreatic cancer. Loss-of-function mutations in several tumor suppressorgenes occur in this disease, including p53, CDKN2A gene (also called multipletumor suppressor-1 gene, leading in many cases to loss of function of p16), DPC4,and BRCA2. A feature almost unique to pancreatic cancer is the combination of K-ras and CDKN2A mutations. Clinical Features Presenting Features Common presenting features of pancreatic cancer include pain (present in>80% of patients with locally advanced or metastatic disease), obstructivejaundice, weight loss, and anorexia. Patients with jaundice may also have pruritus,pale stools, and dark urine; they often have tumors in the pancreatic head, and tendto be diagnosed earlier and with earlier stage disease. Other symptoms tend to bemore insidious, so that in the absence of jaundice, the interval between onset anddiagnosis can be prolonged. Pain, for example, is often more of a problem inpatients with lesions in the body or tail of the pancreas where the primary tumor ismore likely to become quite large or to invade adjacent structures (such as thesplanchnic nerves) before becoming manifest; these patients frequently haveinoperable disease. When present, pain is often felt as a dull ache in the upperabdomen and may radiate to the back, and characteristically may improve uponleaning forward. It may initially be intermittent, and may worsen with meals.These patients may suffer from marked weight loss, which may result from acombination of anorexia, early satiety, malabsorption or diarrhea/steatorrhea.Other less common presenting features include the diagnosis of glucoseintolerance (particularly within 2 years of cancer diagnosis), p ...