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Long-gap esophageal atresia - The development of an experimental model of esophageal regeneration in vivo as an attempt to improve clinical outcome

Doctoral thesis
Authors Linus Jönsson
Date of public defense 2015-01-23
ISBN 978-91-628-9200-5
Publisher University of Gothenburg
Place of publication Göteborg
Publication year 2015
Published at Institute of Clinical Sciences, Department of Pediatrics
Language en
Links hdl.handle.net/2077/37109
Keywords Long-gap esophageal atresia, Follow-up, guided tissue regeneration, small intestinal submucosa, pulmonary physiology, esophageal replacement, extracellular matrix, macrophage phenotype
Subject categories Pediatrics

Abstract

Background: A subset (~8-15%) of the patients born with esophageal atresia (EA) suffer from a lack of esophageal tissue, which makes a primary anastomosis difficult to achieve. This is most common in patients born without a distal fistula between the trachea and the distal esophageal segment. Purpose: To investigate the clinical course and outcome in patients born with long-gap esophageal atresia (LGEA) in the western region of Sweden and to develop an experimental model of guided tissue regeneration in the intrathoracic esophagus. Methods: A retrospective study of 16 consecutive patients born with LGEA between 1995 and 2010 was performed. The patients had been followed according to a structured program at one and seven years of age. The experimental studies had been performed in growing piglets, where 3 cm of the intrathoracic esophagus had been replaced with a silicone stented Biodesign® mesh. The piglets were provided with a gastrostomy through a small midline laparotomy. Factors influencing the clinical and histological outcome had been recorded. In Paper II, six piglets underwent surgery, in Paper III, ten and, in Paper IV, six. Results: No mortality was seen in the patients with LGEA. The mean age at definitive surgery was 147 days. The patients were small for gestational age. Eleven of sixteen (70%) had a delayed primary anastomosis as a definitive procedure, three had a gastroplasty and two underwent a colonic interposition. After surgery, anastomotic leakage was seen in seven of 16 (45%) patients and stricture developed in 11 of 16 (70%). At follow-up, some catch-up in weight was seen at seven years of age, but no catch-up in stature was seen. Spirometry performed at one and seven years of age showed obstruction or restriction in 9 of 14 (55%) measurements. The spirometry findings did not indicate any further need for surgery. Multiple breath washout was within the normal range in 11 of 15 (75%) measurements at one and seven years of age. Three of four (75%) of the patients with a pathological lung clearance index (LCI) at multiple breath washout required further surgery to prevent pulmonary damage due to aspiration. All patients either underwent surgery or were receiving continuous medical treatment for gastroesophageal reflux, and 7 of 16 (45%) had gastrostomy at the end of the study period. All patients were able to drink orally, but two of 16 (13%) were unable to eat solid foods. Conclusion: Patients in our study born with LGEA required long hospitalization and suffered from symptoms related to gatroesophageal reflux during childhood. These individuals were small for gestational age. Some catch-up in weight was seen at seven years of age, but no catch-up in stature was seen. Multiple breath washout might be a valuable tool for the early detection of aspiration into the lungs in this patient group. The experimental model for replacing a part of the intrathoracic esophagus in growing piglets showed that a remodeling inflammatory pattern, accumulation of muscle cells and a structured overall organization in the wall of the bridging graft can be achieved under favorable conditions. Leakage in the anastomoses and stent loss prior to 20 days changed the inflammatory profile and gave rise to scar tissue formation and stricture.

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