Foregut Motility Disorders - a clinical and experimental study

Detta är en avhandling från Stockholm : Karolinska Institutet, Center for Surgical Sciences CFSS

Sammanfattning: Objective: To investigate some clinical aspects and treatment modalities of foregut motility disorders and to experimentally explore some mechanisms involved. Special emphasis has been put on elucidating and evaluating different treatment modalities. The experimental study investigated the possible role for nitric oxide (NO) in foregut motility disorders. Methods: One randomized study explored the possible role for weight reduction treatment on gastroesophageal reflux (GERD) in obese patients. Two other studies examined surgical treatment of achalasia with special attention to the effect on primary symptoms and side effects such as GERD. Furthermore, the risk for reflux esophagitis or other alterations in histology from distal esophageal mucosa was investigated in a retrospective study of patients with achalasia. The outcome after surgical treatment in other spastic esophageal motility disorders was examined during a long-term follow-up study. In an experimental study, nitric oxide synthase knockout mice (nNOS-/-) were compared with wild type mice, and endothelial synthase knockout mice (eNOS-/-) and the role for NO was investigated in relation to gastric emptying. Results: Despite a significant weight reduction, there was no improvement either in GERD symptoms or objective measurements. Laparoscopic myotomy showed good results after the learning curve but with a risk for reflux even though not always symptomatic. Open myotomy showed excellent improvement in the symptoms of dysphagia in the majority of patients, but there was a risk of reflux and related complications. Additional surgery with a total fundoplication had good effects on dysphagia without reflux side effects. Histological changes in the mucosa of the distal esophagus were apparent primarily in achalasia patients formerly treated with surgery or balloon dilatation. The nNOS-/- mice had significantly delayed gastric emptying for solids and liquids, a greater stomach volume and weight, and hypertrophy of the antral circular muscular layer, compared to both wild type mice and eNOS-/- mice. Conclusions: The most common foregut motility disorder, GERD, does not improve after weight reduction in obese patients. The recommended treatment should be medical or surgical. A clinical investigation in foregut motility disorders showed that surgical treatment in achalasia and other spastic esophageal motility disorders improved symptom in the majority of patients. In achalasia, there is a risk for GERD if the myotomy is not combined with an antireflux procedure. This is evident also in histological investigations in patients with achalasia formerly treated with myotomy. The origin of these foregut motility disorders may partly be related to an imbalance in smooth muscle relaxation due to inadequate neurotransmission of NO.

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