Pancreatic cancer
Pancreatic cancer, primarily ductal adenocarcinoma, accounts for about 30,500 cases and 29,700 deaths in the US annually. Symptoms include weight loss, abdominal pain, and jaundice. Diagnosis is by CT. Treatment is surgical resection and adjuvant chemotherapy and radiation therapy. Prognosis is poor because disease is often advanced at the time of diagnosis.
Most pancreatic cancers are exocrine tumors that develop from ductal and acinar cells. Pancreatic endocrine tumors are discussed below.
Adenocarcinomas of the exocrine pancreas arise from duct cells 9 times more often than from acinar cells; 80% occur in the head of the gland. Adenocarcinomas appear at the mean age of 55 yr and occur 1.5 to 2 times more often in men. Prominent risk factors include smoking, a history of chronic pancreatitis, and possibly long-standing diabetes mellitus (primarily in women). Heredity plays some role. Alcohol and caffeine consumption do not appear to be risk factors.
Insulinoma - Pancreatic cancers
An insulinoma is a rare pancreatic β-cell tumor that hypersecretes insulin. The main symptom is fasting hypoglycemia. Diagnosis is by a 48- or 72-h fast with measurement of glucose and insulin levels, followed by endoscopic ultrasound. Treatment is surgery when possible. Drugs that block insulin secretion (eg, diazoxide, octreotide, Ca channel blockers, β-blockers, phenytoin) are used for patients not responding to surgery.
Of all insulinomas, 80% are single and may be curatively resected if identified. Only 10% of insulinomas are malignant. Insulinoma occurs in 1/250,000 at a median age of 50 yr, except in multiple endocrine neoplasia (MEN) type I (about 10% of insulinomas), when it occurs in the 20s. Insulinomas associated with MEN type I are more likely to be multiple.
Surreptitious administration of exogenous insulin can cause episodic hypoglycemia mimicking insulinoma.
Pancreatic Endocrine Tumors
Pancreatic endocrine tumors arise from islet and gastrin-producing cells and often produce many hormones. They have two general presentations. Nonfunctioning tumors may cause obstructive symptoms of the biliary tract or duodenum, bleeding into the GI tract, or abdominal masses. Functioning tumors hypersecrete a particular hormone, causing various syndromes. These clinical syndromes can also occur in multiple endocrine neoplasia, in which tumors or hyperplasia affects two or more endocrine glands, usually the parathyroid, pituitary, thyroid, or adrenals.
Treatment for functioning and nonfunctioning tumors is surgical resection. If metastases preclude curative surgery, various antihormone treatments may be tried for functioning tumors. Because of tumor rarity, chemotherapy trials have not identified definitive treatment. However, streptozotocin has selective activity against pancreatic islet cells and is commonly used, either alone or in combination with 5-fluorouracil or doxorubicin. Some centers use chlorozotocin and interferon.
Zollinger-Ellison Syndrom - Pancreatic cancers
Zollinger-Ellison Syndrom -(Z-E Syndrome; Gastrinoma)
Zollinger-Ellison syndrome is caused by a gastrin-producing tumor usually located in the pancreas or the duodenal wall. Gastric acid hypersecretion and peptic ulceration result. Diagnosis is by measuring serum gastrin levels. Treatment is proton pump inhibitors and surgical removal.
Gastrinomas occur in the pancreas or duodenal wall 80 to 90% of the time. The remainder occur in the splenic hilum, mesentery, stomach, lymph node, or ovary. About 50% of patients have multiple tumors. Gastrinomas usually are small (< 1 cm in diameter) and grow slowly. About 50% are malignant. About 40 to 60% of patients with gastrinoma have multiple endocrine neoplasia.
Vipoma - Pancreatic cancers
A vipoma is a non-β pancreatic islet cell tumor secreting vasoactive intestinal peptide (VIP), resulting in a syndrome of watery diarrhea, hypokalemia, and achlorhydria (WDHA syndrome). Diagnosis is by serum VIP levels, and tumor is localized with CT and endoscopic ultrasound. Treatment is surgical resection.
Of these tumors, 50 to 75% are malignant, and some may be quite large (7 cm) at diagnosis. In about 6%, vipoma occurs as part of multiple endocrine neoplasia.
Glucagonoma - Pancreatic cancers
A glucagonoma is a pancreatic α-cell tumor that secretes glucagon, producing hyperglycemia and a characteristic skin rash. Diagnosis is by elevated glucagon levels and imaging studies. Tumor is localized with CT and endoscopic ultrasound. Treatment is surgical resection.
Glucagonomas are very rare but similar to other islet cell tumors in that the primary and metastatic lesions are slow-growing: 15-yr survival is common. Eighty percent of glucagonomas are malignant. The average age at symptom onset is 50 yr; 80% of patients are women. A few patients have multiple endocrine neoplasia type I.
Small-bowel tumors
Small-bowel tumors account for 1 to 5% of GI tumors.
Benign tumors include leiomyomas, lipomas, neurofibromas, and fibromas. All may cause abdominal distention, pain, bleeding, diarrhea or, if obstruction develops, vomiting. Polyps are not as common as in the colon.
Gastrointestinal stromal tumors
Gastrointestinal stromal tumors (GIST) are tumors of the GI tract derived from mesenchymal precursor cells in the gut wall. They result from mutations of a growth factor receptor gene, C-KIT. Some are caused by previous radiation therapy to the abdomen for other tumors.
Tumors are slow growing, and malignant potential varies from minimal to significant. Most (60 to 70%) occur in the stomach, 20 to 25% in the small bowel, and a small number in the esophagus, colon, and rectum. Average age at presentation is 50 to 60.
Polyps of the Colon and rectum
An intestinal polyp is any mass of tissue that arises from the bowel wall and protrudes into the lumen. Most are asymptomatic except for minor bleeding, which is usually occult. The main concern is malignant transformation; most colon cancers arise in a previously benign adenomatous polyp. Diagnosis is by endoscopy. Treatment is endoscopic removal.
Polyps may be sessile or pedunculated and vary considerably in size. Incidence of polyps ranges from 7 to 50%; the higher figure includes very small polyps (usually hyperplastic polyps or adenomas) found at autopsy. Polyps, often multiple, occur most commonly in the rectum and sigmoid and decrease in frequency toward the cecum. Multiple polyps may represent familial adenomatous polyposis. About 25% of patients with cancer of the large bowel also have satellite adenomatous polyps.
Adenomatous (neoplastic) polyps are of greatest concern. Such lesions are classified histologically as tubular adenomas, tubulovillous adenomas (villoglandular polyps), or villous adenomas. The likelihood of malignancy in an adenomatous polyp at the time of discovery is related to size, histologic type, and degree of dysplasia; a 1.5-cm tubular adenoma has a 2% risk of containing a malignancy, vs. 35% risk in 3-cm villous adenomas.
Familial adenomatous polyposis
Familial adenomatous polyposis is a hereditary disorder causing numerous colonic polyps and resulting in colon carcinoma by age 40. Patients are usually asymptomatic but may have heme-positive stool. Diagnosis is by colonoscopy and genetic testing. Treatment is colectomy.
Familial adenomatous polyposis (FAP) is an autosomal dominant disease in which ≥ 100 adenomatous polyps carpet the colon and rectum. The disorder occurs in 1 in 8,000 to 14,000 people. Polyps are present in 50% of patients by age 15, and 95% by 35. Malignancy develops before age 40 in nearly all untreated patients.
Patients also can develop various extracolonic manifestations (previously termed Gardner’s syndrome), both benign and malignant. Benign manifestations include desmoid tumors, osteomas of the skull or mandible, sebaceous cysts, and adenomas in other parts of the GI tract. Patients are at increased risk for malignancy in the duodenum (5 to 11%), pancreas (2%), thyroid (2%), brain (medulloblastoma in < 1%), and liver (hepatoblastoma in 0.7% of children < 5).
Stomach cancer
Etiology of stomach cancer is multifactorial, but Helicobacter pylori plays a significant role. Symptoms include early satiety, obstruction, and bleeding but tend to occur late in the disease. Diagnosis is by endoscopy, followed by CT and endoscopic ultrasound for staging. Treatment is mainly surgery; chemotherapy may provide a temporary response. Long-term survival is poor except for those with local disease.
Stomach cancer accounts for about 21,000 cases and 12,000 deaths in the US annually. Gastric adenocarcinoma accounts for 95% of malignant tumors of the stomach; less common are localized gastric lymphomas and leiomyosarcomas. Stomach cancer is the 2nd most common cancer worldwide, but the incidence varies widely; it is extremely high in Japan, Chile, and Iceland. In the US, incidence has declined in recent decades to the 7th most common cause of death from cancer. In the US, it is most common in blacks, Hispanics, and American Indians. Its incidence increases with age; > 75% of patients are > 50 yr.
Esophageal tumor
The most common malignant esophageal tumor is squamous cell carcinoma, followed by adenocarcinoma. Symptoms are progressive dysphagia and weight loss. Diagnosis is by endoscopy, followed by CT and endoscopic ultrasound for staging. Treatment varies with stage and generally includes surgery with or without chemotherapy and radiation. Long-term survival is poor except for those with local disease.
Esophageal cancer accounts for about 13,500 cases and 12,500 deaths in the US annually.
