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Pancreatic Cancer

Pancreatic CancerExocrine pancreatic cancer accounts for 95% of all the cancers that arise in the pancreas. Between 75% and 95% of exocrine pancreatic cancers arise from the ductular epithelium. Other cancers, such as acinar cell carcinoma, giant cell carcinoma, adenosquamous carcinoma, mucinous carcinoma, cystadenocarcinoma, papillary cystic tumor, mucinous ductal ectasia, intraductal papillary neoplasm, fibrosarcoma, leiomyosarcoma, and lymphoma are rare and account for less than 10% of the exocrine tumors.

Islet-cell tumors of the pancreas make up approximately 5% of the adenocarcinomas of the pancreas. These tumors often manifest themselves by the hormones they secrete. Tumors secreting gastrin, insulin, glucagon, vasoactive intestinal polypeptide, pancreatic polypeptide, neurotensin, and somatostatin may present as single tumors or as part of multiple neoplasm syndromes.

Epidemiology

The prevalence of carcinoma of the pancreas is nine to ten per 100,000 persons in most western countries. It is the fourth most common cause of death from carcinoma in males (after lung, colon, and prostate) and the fifth in females (after breast, colon, lung, and ovary). It can occur at any age but is most commonly seen in the sixth to eighth decades of life. It is more common in men than in women (1.3:1), in blacks than in whites (incidence 15.2/100,000 black men), and in Jews than in non-Jews.

There has been an increase in the incidence of pancreatic cancer in the last 30 years. Various substances have been implicated as possible etiologic factors. The risk of pancreatic cancer developing is increased 1.5 times in cigarette smokers. The risk increases as the number of cigarettes smoked increases, and the excess risk levels off 10 to 15 years after smoking cessation.

Diets rich in fat, red meat, or both have been implicated as risk factors. There seems to be a protective effect of diets rich in fruits and vegetables, carotenoids, and selenium. Other risk factors include history of peptic ulcer surgery (partial gastrectomy); cholecystectomy, possibly by increasing cholecystokinin secretion; diabetes mellitus; chronic pancreatitis (mostly hereditary and tropical types); and prolonged exposure to the gasoline derivatives, 2-naphthylamine and benzidine. There is no conclusive evidence that use of alcohol or coffee is related to the development of pancreatic cancer.

Pathophysiology

Pancreatic CancerAdenocarcinoma of the pancreas forms a dense, fibrotic mass in the pancreas associated with a desmoplastic reaction. Seventy percent of the lesions are located in the head; the remainder are in the body and the tail of the gland. By itself, the tumor may not cause symptoms. However, because the pancreas, which is a retroperitoneal organ without a mesentery, lies close to the porta hepatis, common bile duct, duodenum, stomach, and colon, the tumor mass may impinge on or penetrate into any of these structures and cause symptoms.

Pancreatic cancer metastasizes widely. It spreads locally by direct extension and to distant sites by lymphatic and vascular channels. It also invades nerves and nervous plexuses, especially in the celiac and mesenteric areas. The most common sites of extralymphatic metastasis are the liver, peritoneum, and lung. Pancreatic tumors other than ductal adenocarcinomas (e.g., cystadenocarcinomas, islet cell tumors) often have a more indolent course. Tumors such as carcinomas of the breast or lung and melanomas may metastasize to the pancreas and present as mass lesions in the organ.

Diagnosis of Pancreatic Cancer

Treatment

To decide on the appropriate mode of treatment for pancreatic cancer, a staging system has been devised.

Stage I: confined to pancreas alone.

Stage II: involving only neighboring structures.

Stage III: involving regional lymph nodes.

Stage intravenous: including liver and other distant spread.

Regardless of the mode of therapy chosen, all patients need to receive intensive supportive and nutritional therapy, either enteral or parenteral, as indicated. The importance of emotional support in this disease, both to the patients and their families, cannot be overstated.

Surgery

Definitive surgery. In a large series of patients with pancreatic cancer, only 5% to 22% had a resectable tumor at the time of diagnosis. The standard operation for pancreatic cancer is pancreaticoduodenectomy (the Whipple’s operation) or a modification of this procedure. The Whipple’s operation consists of en bloc removal of the duodenum, a variable portion of the distal stomach, and the jejunum, gallbladder, common bile duct, and regional lymph nodes, followed by pancreaticojejunostomy and gastrojejunostomy. Vagotomy should be performed if more than 60% of the stomach is removed. Total pancreatectomy does not offer better results; however, it produces exocrine insufficiency and brittle diabetes, which is difficult to manage. In the United States, a less extensive operation that preserves the pylorus and avoids postgastrectomy symptoms is being used with no apparent compromise of long-term survival. In most of these patients, the cancer is at the head of the pancreas.

The 5-year survival of patients who undergo pancreatic resection is 17% to 24% in large centers. There may be a better prognosis for some subgroups of patients such as those with smaller tumors (<2 cm in diameter), patients without lymph node metastases or major vessel involvement, and those with no residual tumor. In such patients, the 5-year survival may be as high as 57%. The mortality of pancreaticoduodenectomy is less than 5% in many centers, and there are fewer complications than previously due to both technologic and procedural advances.

Palliative surgery

Biliary obstruction. In patients with unresectable tumors with biliary obstruction, a bypass procedure may be performed to decompress the biliary tract. The choice of operation depends on the location of the obstruction: A cholecystojejunostomy, choledochojejunostomy, or hepatojejunostomy may be done. Because approximately one third of the patients with ductal adenocarcinoma of the head of the pancreas eventually have duodenal obstruction, a gastrojejunostomy may be performed at the same time to spare the patient a second laparotomy.

Mean postoperative mortality after biliary bypass is about 20% with an average survival of 5.4 months. In debilitated patients, a percutaneous or endoscopically placed biliary stent may decompress the biliary tract and reduce the morbidity and the length of hospitalization. The success rate of stents is more than 85% with less than a 1% to 2% mortality. Patients treated with stents may have more frequent hospital admissions for stent occlusion, recurrent jaundice, and infection. However, the new, expandable metal stents seem to avoid these complications. Duodenal obstruction can be treated only by surgery.

Endocrine cancer. Cancer of the body or tail of the pancreas is invariably diagnosed at a late stage. It is very important, however, to rule out endocrine cancer in these instances by tissue diagnosis, because endocrine tumors are much more amenable to treatment and have a much better prognosis.

Abdominal and back pain. Most patients with pancreatic cancer complain of debilitating abdominal or back pain. The injection of phenol or absolute alcohol around the celiac plexus for the relief of pain is helpful in some patients. This procedure can be done operatively during laparotomy or percutaneously. Narcotics and radiotherapy may also be used.

Chemotherapy. Most patients with stages I and II and some with stage III disease who are reasonable surgical candidates should be treated surgically. However, some patients with stages III and intravenous disease have been treated with single- or multiple- agent chemotherapy with variable results. The drugs used are 5-fluorouracil (5-FU), mitomycin, carmustine (BCNU), lomustine (CCNU), methyl CCNU, and streptozotocin. Response rates have been 20% to 40% in small series. Combination chemotherapeutic regimens are also being tested. Additional controlled studies are needed in this area before chemotherapy can become an established treatment of this disease.

Radiation therapy alone has not been unequivocally successful in the treatment of nonresectable localized cancer of the pancreas. However, the combination of radiation therapy (4000-6000 rad) with chemotherapy (using 5-FU) has been found to result in enhanced radiation therapeutic efficiency. In one study, the survival was increased from 5.5 months to 11 months. Newer radiation techniques using iodine 125 directly implanted into the tumor tissue and neutron beam radiation show promise in the treatment of unresectable cancer of the pancreas.

Intraoperative radiation therapy offers the possibility of delivering higher doses of radiation to the pancreatic cancer with less risk of injury to the adjacent organs. In most centers, a single dose of 20 Gy is delivered to the surgically exposed cancer by an electron beam through a field-limiting cone. Median survivals of 13 to 16 months have been reported with excellent local control. Five percent of patients have lived 3 to 8 years. Relief of pain has been achieved in 50% to 90% of these patients. Unfortunately, in 30% of these patients unavoidable irradiation of the duodenum may result in bleeding, obstruction, and perforation. In most patients, therefore, protective gastrojejunostomy is performed at the same time as the intraoperative radiation.

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