Carcinoid Tumors of the Small and Large Intestines

	Tweet

Relevant Physiology and Pathophysiology
Carcinoid tumors are an interesting group of neoplasms that have their origin in the endocrine argentaffin cells in the small intestinal mucosa (argentaffinomas). They are found incidentally in 0.50% to 0.75% of autopsies. Carcinoid tumors occur frequently in the ileum, where argentaffin cells are more abundant, and 20% of these tumors are multifocal. Histologic criteria do not help the physician to distinguish benign from malignant carcinoid tumors. The tumors are invariably small. About 80% of tumors more than 2 cm in diameter metastasize; those less than 1 cm are almost always benign. Metastases are to local lymph nodes, liver, lung, and bone. Carcinoid tumors may induce a reactive fibrosis in the bowel mesentery, sometimes creating an angulated intestinal segment. Even malignant and metastatic carcinoid tumors are indolent. More than 50% of patients with unresectable local metastases survive 5 years, as do about 30% of those with liver metastases. About 10% of individuals with liver metastases survive more than 10 years.

Laboratory and Other Diagnostic Tests
The biochemical marker for the carcinoid syndrome is increased urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA). More than 30 mg of 5-HIAA is usually excreted in 24 hours by patients with carcinoid syndrome. Less striking increases in urinary 5-HIAA may be found in some patients with malabsorption such as occurs in celiac disease and bacterial overgrowth syndromes. Blood serotonin and 5-hydroxytryptophan levels can now be determined; the latter is helpful if gastric carcinoid is suspected. When urinary 5-HIAA excretion is being tested, patients should avoid drugs that may produce false-positive test results, most notably glyceryl guaiacolate, phenothiazines, and methenamine mandelate. Foods rich in serotonin should also be avoided. These include pineapples, bananas, avocados, and walnuts.

Carcinoid tumors may secrete a variety of other hormones, including insulin, adrenocorticotropic hormone, melanocyte-stimulating hormone, gastrin, and glucagon. The endocrine cells from which carcinoid tumors originate are part of the amine content, precursor uptake, and decarboxylation (APUD) family. Foregut carcinoid tumors have also been associated with pluriglandular adenomatoses (e.g., pituitary, adrenal, and parathyroid tumors) and with pancreatic gastrinomas.

Differential Diagnosis
Carcinoid tumors of the small bowel seldom ulcerate and bleed and are usually too small to cause obstruction. They may, however, produce transient intussusceptions and cause cramping abdominal pain and diarrhea. These symptoms may be long standing and intermittent, suggesting irritable bowel syndrome or Crohn’s disease.

In about one third of patients with liver metastases, carcinoid syndrome, which occurs rarely with only nodal metastases, develops. Carcinoid syndrome is characterized primarily by episodes of flushing and diarrhea. The flush may produce a cyanotic appearance, and if attacks are prolonged, facial edema and telangiectasis may develop. The mediator of the carcinoid flush is unknown. Kallikrein, bradykinin, other kinin peptides, substance P, prostaglandins, serotonin, and histamine have been implicated. The flush has been precipitated by ingestion of a meal and by administration of ethanol, calcium, epinephrine, isoproterenol, and pentagastrin. The diarrhea and cramps in this syndrome appear to be related to the production of serotonin (5-hydroxytryptamine).

Bronchial spasm is often part of carcinoid syndrome, and wheezing may become a prominent feature. Right-sided heart lesions, particularly pulmonary and tricuspid valvular fibrosis, may develop with associated murmurs of pulmonary stenosis and tricuspid insufficiency. Right-sided congestive heart failure may produce further hepatomegaly, ascites, pulmonary congestion, and edema.

Diarrhea in carcinoid syndrome is usually watery, episodic, and associated with abdominal cramping and loud borborygmi. Gastric carcinoids that tend to produce more 5-hydroxytryptophan than serotonin and that also may produce histamine usually are not associated with diarrhea.

Most patients with carcinoid syndrome have liver metastases, which are usually evident on physical examination and liver scans. Carcinoid tumors with nodal metastases that produce the syndrome may cause a palpable abdominal mass. Ovarian carcinoid tumors are usually detected by abdominal or pelvic examination, and bronchial carcinoid tumors by chest radiography.

Management
Carcinoid tumors of the small bowel should be surgically resected. If metastatic disease is present, the approach remains the same as in other bowel malignancies. In patients with the carcinoid syndrome all treatment must be carefully monitored and controlled to prevent precipitating a carcinoid crisis. Chemotherapy has had some benefit in unresectable disease, but treatment efforts, in general, should be tempered by the usually indolent growth of these tumors. A variety of antiserotonin agents, antihistamines, antiadrenergics, antiprostaglandins, and steroids have been helpful in the carcinoid syndrome, but benefits must be weighed against side effects. Intravenous somatostatin has been used to ameliorate acute symptoms, and subcutaneous somatostatin analogs have become important agents for successful long-term control.

Author: Charles J. Lightdale

BIBLIOGRAPHY

_{Basson MD, Ahlman H, Wangberg B, Modlin IM: Biology and management of the midgut carcinoid, Am J Surg 165:288, 1993.}

DiSario JA, Burt RW, Vargas H et al: Small bowel cancer: epidemiological and clinical characteristics from a population-based registry, Am J Gastroenterol 89:699, 1994.

Fearon ER, Vogelstein B: A genetic model for colorectal tumorogenesis, Cell 61:759, 1990.

Harris AG, Redfern JS: Octreotide treatment of carcinoid syndrome: analysis of published dose-titration data, Aliment Pharmacol Ther 9:387, 1995.

Moertel BC et al: Levamisole and fluorouracil for adjuvant therapy of resected colon carcinoma, N Engl J Med 322:352, 1990.

Rex DK, Rahmani EY, Haseman JH et al: Relative sensitivity of colonoscopy and barium enema for detection of colorectal cancer in clinical practice, Gastroenterology 112:17, 1997.

RELATED STORIES:
Anal Carcinoma   Benign tumors of the small intestine   Malignant tumors of the large intestine   Malignant Tumors of the Small Intestine   Hereditary nonpolyposis colorectal carcinoma   Benign tumors of the large intestine

Comments

[ + Post Your Own ]

Now you're in the public comment zone. What follows is not Armenian Medical Network's stuff; it comes from other people and we don't vouch for it. A reminder: By using this Web site you agree to accept our Terms of Service. Click here to read the Rules of Engagement.

There are no comments for this entry yet. [ + Comment here + ]