Mega-Intestine After Subtotal Colectomy for Constipation

Abstract

t A male with multiple endocrine neoplasia (MEN) type 2B presented with chronic abdominal distention and onstipation. He had previously undergone total thyroidectomy or medullary thyroid carcinoma, and a subtotal colectomy with leosigmoidostomy for megacolon. Examination revealed a maranoid body habitus, neuromas on the tip of the tongue, pectus xcavatum, and severe abdominal distention. Laboratory studies ere unremarkable, including negative urine catecholamines creening for pheochromocytoma. Abdominal x-ray showed muliple dilated loops of small bowel (Figure A). At laparotomy, ilated loops of small bowel with maximum diameter of 8 cm were oted (Figure B). The patient underwent sigmoid resection with nd ileostomy. On microscopic examination, the sigmoid and erminal ileum revealed hyperplasia of the nerve plexuses and an ncreased density of ganglia, many of which showed dysplastic hanges (Figure C, inset, yellow arrow). Hyperplastic subserosal erve fibers were also identified (Figure C, inset, black arrow). Intestinal ganglioneuromatosis associated with MEN type 2B as confirmed by the identification of dysplastic ganglion cells in oth resected sigmoid and terminal ileum. Intestinal ganglioneuomatosis (gangliocytic dysplasia) is characterized by hyperplasia f myenteric or submucosal nerve plexuses with increased number nd size of dysplastic ganglia, and hyperplastic subserosal nerves.1 MEN 2B results from an autosomal dominant mutation with a high degree of penetrance. The mutation involves a gain of function of the RET (rearranged during transfection) proto-oncogene (that encodes a tyrosine kinase receptor) on chromosome 10. The mutation appears to induce growth and differentiation in several developing tissues including those derived from the neural crest.2 In a 28-patient series, 93% of patients with MEN 2B had gastrointestinal symptoms 1 to 24 years before the diagnosis of MEN 2B. Symptoms included flatulence (86%), abdominal distention or being underweight as a child (64%), abdominal pain (54%), constipation or diarrhea (43%), difficulty swallowing (39%), vomiting (14%), and 29% underwent surgery.2 In a series of 16 patients, 90% had colonic disturbances, typically chronic constipation from birth. Megacolon developed in 14 patients, and 8 required colonic surgery.3 Postoperatively, the patient received oral pyridostigmine 60 mg 4 times a day, and supplemental parenteral nutrition. One month later, he was asymptomatic, on regular (full) oral diet and pyridostigmine, and intestinal loops were not dilated on abdominal radiograph. Management of abdominal distension and constipation in MEN 2B is usually conservative with laxatives; however some patients require total colectomy and oral prokinetic agents. Our patient responded to acetyl cholinesterase inhibition (pyridostigmine). The potential efficacy of 5-hydroxytryptamine (5HT)4 agonists, other prokinetics, and stem cell therapy for intesinal ganglioneuromatosis associated with MEN 2B are unclear.