Pancreatic Tumors

Pancreatic tumors include exocrine and endocrine tumors. The only significant benign exocrine pancreatic tumor is cystadenoma, which usually occurs in the body and tail of the pancreas in middle-aged and elderly women. Surgical resection may be needed for diagnosis and relief of symptoms from a large mass. Endocrine tumors are rare in the elderly and arise from the neuroendocrine cells of the pancreas predominantly in the islets of the pancreatic body and tail. The types and treatment of endocrine tumors are listed in Table 113-1.

Pancreatic Cancer

Pancreatic cancer is the second most common GI cancer in the USA with about 29,000 new cases diagnosed annually, > 20,000 of which occur in patients > 65. The incidence increases with age and is 10 times greater in men > 75 years than in the general population; it is the fifth leading cause of cancer death.

A number of carcinogenic factors and disease states are associated with pancreatic cancer, although their causative role is not fully established. These factors include chronic cigarette smoking, a diet high in animal fat, alcohol, diabetes mellitus, and chronic pancreatitis (idiopathic and hereditary).

Ductal cell adenocarcinoma accounts for 75 to 96% of all cancers arising from the pancreas. Other types include giant cell carcinoma, adenosquamous carcinoma, cystadenocarcinoma, and lymphoma. Giant cell carcinoma, also called carcinosarcoma, is a highly malignant lesion with distant metastases occurring early. Adenosquamous carcinoma occurs predominantly in men, more often in patients with a history of radiation therapy. Cystadenocarcinoma, a low-grade malignancy, has the best prognosis because only 20% of cases have metastasized by the time of surgery. Pancreatic lymphoma accounts for 2% of all non-Hodgkin's lymphomas and may be of B-cell or T-cell origin. Eighty percent of pancreatic lesions occur in the head of the pancreas, and 20% in the body and tail.

Symptoms and Signs

The clinical features of pancreatic cancer often depend on the location of the lesions. Patients with lesions of the pancreatic head often present with painless jaundice and acholic stools from common duct obstruction or with nausea and vomiting from gastric outlet obstruction. Pruritus may accompany jaundice. The onset of symptoms in patients with lesions of the pancreatic body and tail is more insidious, amounting to little more than weight loss and vague abdominal or back pain. Symptoms precede diagnosis by about 3 to 6 months. In 70 to 80% of patients with ductal cell adenocarcinoma, advanced stages with locoregional invasion or metastatic spread are present at diagnosis.

Other findings include depression, thromboembolic phenomena, GI bleeding from gastric varices secondary to splenic vein thrombosis, polyarthritis, and diarrhea caused by exocrine pancreatic insufficiency. The onset of diabetes mellitus or a worsening of preexisting diabetes warrants an evaluation for pancreatic cancer.

Early in the disease, there are no findings on physical examination. Later, jaundice, an epigastric mass, supraclavicular lymphadenopathy, hepatomegaly, or a large, palpable gallbladder may be noted. Painless jaundice and a palpable gallbladder (Courvoisier's sign) combined with acholic stools are highly suggestive of cancer of the pancreatic head.

Diagnosis

Early diagnosis when the tumor is still resectable is unusual and occurs only in patients with cancer of the pancreatic head who present with early jaundice. Abdominal ultrasound may be helpful, but CT is better able to visualize a pancreatic mass and establish its relationship with surrounding tissues. In up to 90% of cases, endoscopic retrograde cholangiopancreatography can detect the tumor with the characteristic findings of ductal irregularity and cutoff. Cytohistologic diagnosis may be performed by fine-needle aspiration biopsy or pancreatic duct brushing. Detection of K-ras mutations by DNA amplification from pancreatic aspirates or pancreatic juice may increase the diagnostic use of such techniques. Serologic tumor markers, including CEA and CA 19-9, may be elevated in some cases but are generally not useful clinically.

Assessment of tumor resectability warrants not only a combination of different preoperative radiologic examinations (CT, MRI, and endoscopic ultrasound), but also laparoscopy in some centers when findings are inconclusive.

Prognosis and Treatment

Advanced pancreatic adenocarcinoma has a grim prognosis, with a median survival of 4 months and a 5-year probability of survival of 2%.

Surgery is the only potentially curative therapy for pancreatic cancer. Patients with nonmetastatic, localized, resectable lesions in the pancreatic head may be candidates for pancreatoduodenectomy (Whipple's operation). Although data in the elderly are minimal, mortality and survival rates in patients > 70 seem to be similar to those for younger patients--perioperative mortality rate of 5%, morbidity rate of 45%, and 5-year probability of survival rate of 21%. Therefore, surgery should be considered for the elderly patient with limited disease and appropriately managed comorbid illnesses. However, only 10 to 20% of patients with ductal cell carcinoma fulfill these conditions. For the remainder (and thus the vast majority) of patients, treatment options are less clear. Some elderly patients may do best without any treatment. For other patients, the only procedure that can be performed is a palliative bypass (eg, cholecystojejunostomy or choledochojejunostomy to relieve distal bile duct obstruction or gastrojejunostomy for gastric outlet obstruction); obstructive jaundice can be managed with a biliary stent, placed either endoscopically or radiologically, using transhepatic cholangiography.

Chemotherapy produces little response and no long-term benefit in patients with pancreatic adenocarcinoma. 5-Fluorouracil is the most widely studied drug, is tolerated relatively well in the elderly, and has a response rate of about 15%. Gemcitabine may improve the quality of life by reducing pain medication requirements and improving nutritional status. Nevertheless, there has been no difference in survival when comparing patients who received chemotherapy with those who received only supportive care. Radiation therapy offers minimal benefit, except for palliation of retroperitoneal disease.

Attention must be paid to the treatment of pain in elderly patients. Generally, abdominal pain is treated with analgesics or oral opioids. However, a celiac axis nerve block may be needed for severe, unremitting pain. Pruritus from jaundice may be relieved with antihistamines or cholestyramine 4 g po 1 to 4 times daily. (Cholestyramine is only effective for patients with partial biliary obstruction and is ineffective in completely obstructed patients.) Pancreatic insufficiency can be managed with pancreatic enzymes.

Because many patients present with advanced pancreatic cancer, curative therapy is difficult. Therefore, attention must be paid to patients' quality of life, especially nutritional status and pain relief, along with end-of-life issues.