Intestinal carcinoid tumor

FIGURE 36-2. Recommendations for treating chronic diarrhea. Follow these steps (1) Perform a careful history and physical examination. (2) The possible causes of chronic diarrhea are many. These can be classified into intestinal infections (bacterial or protozoal), inflammatory disease (Crohn s disease or ulcerative colitis), malabsorption (lactose intolerance), secretory hormonal tumor (intestinal carcinoid tumor or VIPoma), drug (antacid), factitious (laxative abuse), or motility disturbance (diabetes mellitus, irritable bowel syndrome, or hyperthyroidism). (3) If the diagnosis is uncertain, selected appropriate diagnostic studies should be ordered. (4) Once diagnosed, treatment is planned for the underlying cause with symptomatic antidiarrheal therapy. (5) If no specific cause can be identified, symptomatic therapy is prescribed. 

Octreotide, a synthetic octapeptide analog of endogenous somatostatin, is prescribed for the symptomatic treatment of carcinoid tumors and vasoactive intestinal peptide-secreting tumors (VIPomas). Metastatic intestinal carcinoid tumors secrete excessive... 

Rabban JT, Lerwill ME, McCluggage WG, et al. Primary ovarian carcinoid tumors may express CDX-2 A potential pitfall in distinction from metastatic intestinal carcinoid tumors involving the ovary. Int J Gynecol Pathol. 2009 28 41-48. 

B. Indications and use Sandostatin is indicated to reduce blood levels of growth hormone and IGF-I (somatomedin-C) in acromegaly patients who have had inadequate response to or cannot be treated with surgical resection, pituitary irradiation, or bromocriptine mesylate at maximally tolerated doses. It is also indicated for the symptomatic treatment of patients with metastatic carcinoid tumors, where it suppresses or inhibits the severe diarrhea and flushing episodes associated with the disease, and for the treatment of the profuse watery diarrhea associated with VIP (vasoactive intestinal peptide)-secreting tumors (vipomas). 

Treatment of carcinoid and vasoactive intestinal peptide acromegaly (reduce blood levels of growth hormone), symptomatic treatment of metastatic carcinoid tumors, and profuse water diarrhea associated with intestinal tumors... 

Focusing our attention on the serotonin branch of Figure 20.21, it is seen that the initial hydroxylation reaction requires tetrahydrobiopterin, which was introduced in Chapter 16 and is discussed further here. Serotonin per se is a neurotransmitter, and it can give rise to melatonin in the pineal gland. Melatonin is synthesized at night, and is believed to be associated with the phenomenon of circadian rhythms. Serotonin is metabolized to 5-hydroxyindoleacetic acid, which is excreted in the urine. Normal 5-hydroxyindoleacetic add excretion is about 7 mg/day, whereas in carcinoid tumor patients, this may be as high as 400 mg/day. Carcinoid is an intestinal tumor that may metastasize into the liver. 

Ml) Carcinoid tumor. Elevated 5-hydroxyindole acetate (5-HIAA) occurs in carcinoid tumors of the intestine, where argentaffin cells secrete excess 5-hydroxytryptamine (serotonin). The patient experiences flushing, diarrhea, hypotension, and bronchoconstriction. (It is possible that these symptoms may relate to other chemidals also produced by argentaffin cells). 

There has been concern about the potential for proton pump inhibitors to cause enterochromaffin-hke cell hyperplasia, gastric carcinoid tumors and gastric cancers, colorectal polyps and adenocarcinoma, atrophic gastritis, and intestinal metaplasia in patients with H. pylori infection, and bacterial overgrowth. 

A powerful new synthetic peptide that mimics the action of somatostatin, octreotide acetate (Sandostatin). is approved by the Food and Drug Administration (FDA) for (he treatment of certain rare forms of intestinal endocrine cancers, such as malignant carcinoid tumors and vasoactive intestinal peptide-secreting tumors (VIPomas). Octreotide acetate is indicated for long-term treatment of severe diarrhea associated with these carcinomas. 

Octreotide (Sandostatin) injection is commercially available in the United States for subcutaneous or intravenous administration. A long-acting intramuscular formulation of octreotide (Sandostatin EAR) is also available for monthly administration. In addition to the treatment of acromegaly, octreotide has many other therapeutic uses, including the treatment of carcinoid tumors, vasoactive intestinal peptide tumors (VIPomas), gastrointestinal fistulas, variceal bleeding, diarrheal states, and irritable bowel syndrome. 

Adenocarcinomas account for more than 90% of tumors of the large intestine. Other histologic types such as mucinous adenocarcinoma, signet-ring adenocarcinoma, carcinoid simplex, and carcinoid tumors occur less frequently. Adenocarcinomas are assigned one of three... 

Jaffee IM, Rahmani M, Singhal MG, Younes M. Expression of the intestinal ttansctiption factor GDX2 in carcinoid tumors is a marker of midgut otigin. Arch Pathol Lab Med. 2006 130 1522-1526. 

FIGURE 18.46 Carcinoid tumors in the ovary can be found with other tissues as a component of a teratoma. They can aiso be primary in the ovary but not associated with other teratomatous tissues, in which case they are viewed as monodermai teratomas. Finaiiy, they can be metastatic from the appendix, smaii intestine, or other sites. Regardiess of their origin, they show cytopiasmic staining for chro-mogranin, as shown here, and for synaptophysin. 

It should be mentioned that / -chlorophenylalanine (fenclonine) is an irreversible inhibitor of tryptophan hydroxylase, the first and rate-determining step in serotonin synthesis. Even though the efficiency of this decrease in 5HT may be as high as 90%, sedation does not result. Reserpine alkaloids, which also deplete 5HT and NE, are sedative. That leaves catecholamine depletion as relevant to sedation. It is interesting that p-chloropheny-lalanine is used to treat carcinoid syndrome, which is a nonmalignanf intestinal mucosal tumor pouring prodigious amounts of 5HT into the circulation. 

Approved uses for the drug include the control of diarrhea associated with vasoactive intestinal peptide tumors and metastatic carcinoid tumors. Other uses include the control of diarrhea associated with AIDS and with pituitary tumors. 

Octreotide acetate (Sandostatin) 1.02 13.6L 1.7-1.9 SC (1.0) IM (0.60-0.63) Severe diarrhea caused by carcinoid tumors or tumors secreting vasoactive intestinal peptide acromegaly... 

A number of genetic diseases that result in defects of tryptophan metabolism are associated with the development of pellagra despite an apparently adequate intake of both tryptophan and niacin. Hartnup disease is a rare genetic condition in which there is a defect of the membrane transport mechanism for tryptophan, resulting in large losses due to intestinal malabsorption and failure of the renal resorption mechanism. In carcinoid syndrome there is metastasis of a primary liver tumor of enterochromaffin cells which synthesize 5-hydroxy-tryptamine. Overproduction of 5-hydroxytryptamine may account for as much as 60% of the body s tryptophan metabolism, causing pellagra because of the diversion away from NAD synthesis. 

Intestinal pseudoobstruction is also part of paraneoplastic syndromes. The anti-/zu antibodies are useful to indicate this condition, as shown in bronchial small cell carcinoma [171], In pheochromocytoma [172] and carcinoid [173] neuromediators affecting small bowel motility are produced by the tumor cells. Intestinal pseudoobstruction has also been reported in neuroblastoma [174],... 

Control of symptoms in patients with metastatic carcinoid (severe diarrhea and flushing episodes) and vasoactive intestinal peptide-secreting tumors (profuse water y diarrhea)... 

Octreotide is a long-acting somatostatin analog that inhibits the secretion of serotonin, vasoactive intestinal peptide, gastrin, motilin, insulin, glucagons, secretin, and pancreatic polypeptide. It is used for the control of symptoms in patients with carcinoid and vasoactive intestinal peptide-secreting tumors (VIPomas). Its major toxicity is nausea and vomiting. 

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