Pancreatic Cancer Symptoms

Symptoms of Pancreatic Cancer

More than 90% of pancreatic cancers are ductal adenocarcinomas, with islet cell tumors constituting the remaining 5 to 10%. Pancreatic cancers occur twice as frequently in the pancreatic head (70% of cases) as in the body (20%) or tail (10%) of the gland.

The incidence of pancreatic carcinoma in the United States has increased significantly as the median life expectancy of the American population has lengthened. The tumor results in the death of >98% of afflicted patients. 28,200 individuals died of pancreatic cancer in 2000, making it the fifth most common cause of cancer-related mortality. The disease is more common in males than in females and in blacks than in whites. It rarely develops before the age of 50.

Despite the availability of serologic tests for tumor-associated antigens, such as the carcinoembryonic antigen (CEA) and CA 19-9, and noninvasive imaging techniques, such as computed tomography (CT) and ultrasonography, the early diagnosis of a potentially resectable pancreatic carcinoma remains extremely difficult.

What is the cause of pancreatic cancers?

Little is known about the causes of pancreatic cancer. Cigarette smoking is the most consistent risk factor, with the disease being two to three times more common in heavy smokers than in nonsmokers. Whether this association is due to a direct carcinogenic effect of tobacco metabolites on the pancreas or an as yet undefined exposure that occurs more frequently in cigarette smokers is uncertain. Patients with chronic pancreatitis are at increased risk of pancreatic cancer, as are persons with long-standing diabetes mellitus. Obesity is a risk factor for pancreatic cancer; risk is directly related to increased calorie intake. Alcohol abuse or cholelithiasis are not risk factors for pancreatic cancer. Nor is pancreatic cancer associated with coffee consumption. Mutations in K-ras genes have been found in >85% of specimens of human pancreatic cancer. Pancreatic cancer has been associated with mutation of the p16INK4 gene located on chromosome 9p21, a gene also implicated in the pathogenesis of malignant melanoma.

What are the symptoms and signs of pancreatic cancers?

With the exception of jaundice, the initial symptoms associated with pancreatic cancer are often insidious and are usually present for >2 months before the cancer is diagnosed (Table 92-1). Pain and weight loss are present in >75% of patients. The pain typically has a gnawing, visceral quality, occasionally radiating from the epigastrium to the back. Pain is often a more severe problem in lesions arising in the body or tail of the gland, as such tumors may become quite large before being detected. Characteristically, the pain improves somewhat when the patient bends forward. The development of significant pain suggests retroperitoneal invasion and infiltration of the splanchnic nerves, indicating that the primary lesion is advanced and is not surgically resectable. Rarely, such pain may be transient and associated with hyperamylasemia, indicative of acute pancreatitis caused by ductal obstruction by tumor. The weight loss observed in most patients is primarily the result of anorexia, although in the initial period of the disease, subclinical malabsorption may also be a contributing factor.

Jaundice due to biliary obstruction is found in >80% of patients having tumors in the pancreatic head and is typically accompanied by dark urine, a claylike appearance of stool, and pruritus. In contrast to the "painless jaundice" sometimes observed in patients having carcinomas of the bile ducts, duodenum, or periampullary regions, most icteric individuals with ductal carcinomas of the pancreatic head will complain of significant abdominal discomfort. Although the gallbladder is usually enlarged in patients with carcinoma of the head of the pancreas, it is palpable in <50% (Courvoisier's sign). However, the presence of an enlarged gallbladder in a jaundiced patient without biliary colic should suggest malignant obstruction of the extrahepatic biliary tree.

Glucose intolerance, presumably a direct consequence of the tumor, often develops within 2 years of the clinical diagnosis. Other initial manifestations include venous thrombosis and migratory thrombophlebitis (Trousseau's syndrome), gastrointestinal hemorrhage from varices due to compression of the portal venous system by tumor, and splenomegaly caused by cancerous encasement of the splenic vein

Treatment of Pancreatic Cancer

Complete surgical resection of pancreatic tumors offers the only effective treatment for this disease. Unfortunately, such "curative" operations are only possible in 10 to 15% of patients with pancreatic cancer, usually those individuals with a tumor in the pancreatic head in whom jaundice was the initial symptom. Patients considered for such a procedure should have no evidence of metastatic spread on a chest radiograph and abdominal-pelvic CT scan and should be operated on by an experienced surgeon, as mortality rates of >15% have been associated with this procedure. Curative resection is usually preceded by laparoscopic inspection of the abdomen to confirm absence of occult disease spread to the omentum, peritoneum, or liver, which would preclude curative resection.

Chemotherapy in the management of patients with widely metastatic pancreatic cancer has been disappointing. Gemcitabine, a deoxycytidine analogue, produces improvement in the quality of life for patients with advanced pancreatic cancer. However, duration of survival is only moderately improved. Newer forms of treatment, including combining gemcitabine with other cytotoxic agents or therapies directed at specific molecular targets, such as K-ras, or p53 are being evaluated.

Cancer Tip

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