Hirschsprung´s Disease & Gastroesophageal Reflux. Aspects on Two Gastrointestinal Motility Disorders in Childhood

Abstract: Gastrointestinal motility disorders are common in childhood and in this thesis we look at two of them, i.e. Hirschsprung´s Disease (HD) and gastroesophageal reflux disease (GERD) in five different studies. HD is a congenital disease characterized by an abscence of ganglion cells in myenteric and submucous ganglia, most commonly in the distal part of the large bowel. In Paper I, we have studied the CART peptide (cocaine-and amphetamine regulated transcript), in human bowel prepararions and were able to show for the first time that the CART peptide is localized in normal human bowel. It is primarily expressed in the myenteric ganglia with high colocalization with the neurotransmitters VIP (vasoactive intestinal peptide) and NO (nitric oxide) indicating a functional role in the intestinal wall. CART-IR (immunoreactive) neurons were not found in the aganglionic part of the bowel indicating an intrinsic origin of the peptide. In Paper II the quality of life (QoL) of adults operated on for HD in their childhood was studied. For that, two validated questionnaires were used, SF-36 health survey and GIQLI (gastrointestinal quality of life index). We found that the adults operated on for HD in childhood, had generally normal QoL. The women, however, had worse general and mental health when compared to the normal population. It was also noted that the longer the aganglionic segment was, the more affected the QoL of the patient. In Paper III we compared the outcome, after two year follow-up, of the Duhamel pull-through operation for rectosigmoid HD and the TERPT (transanal endorectal pull-through) method which we introduced in 2005 in Lund. The study showed that patients operated on with the TERPT-method recovered significantly faster and required fewer interventions during follow-up time, without compromising the functional results. Also the cosmetic results were far better for TERPT group. Our result support the use of the TERPT method in favor of the Duhamel pull-through for rectosigmoid HD. PH-monitoring is valuable in the diagnosis of GERD and the gold standard has been catheter-based monitoring. In Paper IV-V we have shown that a wireless esophageal pH-monitoring system is feasible for use and well-tolerated by children, and is to be recommended. Our result found no clear advantage of esophageal pH-monitoring for 48 hours compared to 24 hours in the diagnosis of GERD in children. It was also shown that it is the combination of symptoms, endoscopic findings, pH-monitoring results and pathological examination that gives the most reliable diagnosis of GERD in children.