Immunohistochemical evaluations of ultrashort-segment Hirschsprung's disease

Departments of Medicine and Surgery University of Wisconsin Madison Wisconsin
Diseases of the Colon & Rectum (Impact Factor: 3.75). 06/1996; 39(7):817-822. DOI: 10.1007/BF02054450


PURPOSE: Unlike classic Hirschsprung's disease, short-segment and ultrashort-segment varieties are usually found to be latent and milder. Ultrashort-segment Hirschsprung's disease may present as intractable chronic constipation in children over one year of age, adolescents, and adults. Anorectal myectomy has been shown in many instances to provide effective long-term treatment for certain patients with ultrashort-segment Hirschsprung's disease. Histologically, the affected segment in Hirschsprung's disease has been shown to have increased cholinergic nerves, lack of nitric oxide synthase-containing neuronal elements, and show moderate to severe loss of myenteric neurons. METHODS: Here, we report three cases that showed clinical and manometric evidence of ultrashort-segment Hirschsprung's disease. Two of the three patients responded well to myectomy. RESULTS: Detailed histologic and immunohistochemical evaluation of the internal anal sphincter and a comparison with three normal controls revealed absence of nitric oxide synthase-containing neurons in both cases that responded well to surgery and continued presence of these neurons in the patient who did not respond. A review of the current literature on various treatment modalities is included. CONCLUSIONS: Anorectal myectomy provides long-term relief of this chronic problem in a subgroup of patients with ultrashort-segment Hirschsprung's disease who lack nitrinergic neurons at the internal anal sphincter.

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    ABSTRACT: Aim: The term ultra short is not clearly defined in ultrashort-segment Hirschsprung's disease. The limited extent of the ultrashort-segment Hirschsprung's disease allows for the treatment with extended sphincteromyectomy. This procedure could be diagnostic and therapeutic one. The study was designed to evaluate the role of posterior myectomy in children with refractory constipation in the diagnosis and treatment of ultrashort-segment Hirschsprung's disease. Methods: A descriptive cross sectional study was carried out among 40 pediatric patients (1 – 12 years) with refractory constipation without obvious organic causes. Detailed history, examination, barium enema and anorectal manometry were performed to all children. Posterior anorectal myectomy was performed to the studied patients. The outcome and postoperative complications were assessed for all children. Results: Agangliosis was diagnosed in 24 patients (60%) among whom constipation was improved in 75% while it was improved among (50%) of the ganglionic group. Abdominal distension, soiling and anorectal manometric studies were markedly improved after surgery in both aganglionic and ganglionic groups. Rare postoperative complications were reported among only five patients (12.5%). Conclusion: Anorectal myectomy is an effective procedure in managing refractory constipation in pediatrics and also for the diagnosis of Ultrashort segment Hirschsprung's disease and is curative in such cases.
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    ABSTRACT: The pathogenesis of Hirschsprung's disease is not well understood. The suitability of the animal model for the unknown pathogenesis of inhibitory neurotransmission in Hirschsprung's disease was investigated. Circular smooth muscle strips from the internal anal sphincter (IAS) and distal colon (2, 6, 8, 16, and 24 mm from the anal verge) from normal and Ls/Ls mice (mice homozygous for the lethal spotting mutation that develop fetal megacolon after aganglionosis of the terminal colon) were prepared to record changes in isometric tensions in response to different agents and nonadrenergic, noncholinergic nerve stimulation by electrical field stimulation. Bethanechol was used to produce contraction of the smooth muscle strips of distal colon to record a decrease in the tension. Conversely, the IAS smooth muscle strips developed spontaneous tone. In the normal homozygous mice, electrical field stimulation caused a biphasic response, an initial decrease followed by an after-contraction, whereas in Ls/Ls mice, the predominant response was contraction. All smooth muscle strips from normal and Ls/Ls mice produced relaxation in response to sodium nitroprusside and vasoactive intestinal polypeptide. Ls/Ls mice may serve as an appropriate animal model to investigate the pathogenesis of the inhibitory neurotransmission in Hirschsprung's disease in the distal colon and IAS.
    Gastroenterology 05/1997; 112(5):1575-85. DOI:10.1016/S0016-5085(97)70039-8 · 16.72 Impact Factor
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    ABSTRACT: The pathophysiology of Chagas' disease is incompletely understood. Neuronal nitric oxide has been cited as a candidate neurotransmitter responsible for relaxation of the internal anal sphincter. Neuronal nicotinamide adenine dinucleotide phosphate diaphorase can be used as a marker for neuronal nitric oxide synthase. This study was designed to examine the alterations of the nitric oxide-containing neurons in the enteric nervous system of the colon of patients who underwent resections for advanced megacolon and to compare these specimens with small-bowel specimens from the same patients and with specimens from control subjects. Specimens from resected rectum and extramucosal small-bowel biopsy specimens from 11 patients with Chagas megacolon but no apparent small-bowel clinical involvement were compared with the uninvolved colon and jejunum of 10 control patients with colon cancer. Tissues were fixed in Zamboni solution and evaluated by histochemistry for nicotinamide adenine dinucleotide phosphate diaphorase-containing neurons. Reactivity was evaluated on a 0 to 4 scale in the longitudinal muscle, myenteric plexus, circular muscle, submucosal plexus, and mucosa. Specimens from control patients showed well-stained myenteric and submucosal neurons and an abundant network of terminal nerve fibers in the muscle layers. Chagasic specimens had decreased staining in all layers of the gut. Overall there was a statistically significant decrease in nicotinamide adenine dinucleotide phosphate diaphorase-containing neurons. Biopsy specimens from clinically uninvolved small bowel of patients with Chagas' disease also showed decreased reactivity, but to a lesser degree. Nicotinamide adenine dinucleotide phosphate diaphorase activity is decreased in patients with advanced megacolon. The alterations are more relevant in the myenteric plexus and the circular muscle. Reactivity is also diminished in the clinically uninvolved small bowel, but to a lesser extent.
    Diseases of the Colon & Rectum 12/1998; 41(11):1411-7. DOI:10.1007/BF02237058 · 3.75 Impact Factor
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