Alternations in Genes Expression of Pathway Signalling in Oesophageal Tissue with Atresia: Results of Transcript Expression Microarray Profiling

428 ABSTRACTS FROM THE 2012 ESAPHAGEAL ATRESIA CONFERENCE DISEASES OF THE ESOPHAGUS ABSTRACT 1 – oral ABSTRACT 3 – oral ALTERNATIONS IN GENES EXPRESSION OF PATHWAY SIGNALLING IN OESOPHAGEAL TISSUE WITH ATRESIA: RESULTS OF TRANSCRIPT EXPRESSION MICROARRAY PROFILING Smigiel R, Patkowski D, Lebioda A, Blaszczyaaski M, Korecka K, Czauderna P, Korlacki W, Jakubiak A, Bednarczyk D, Maciejewski H, Wizinska P, Sasiadek MM Genetics Dep., Wroclaw Medical University, Wroclaw, Poland, robert. CONTEMPORARY SURVIVAL OF SYNDROMIC ESOPHAGEAL ATRESIA Teague W, McLeod E, Hawley A, Brooks J, Nightingale M, Clarnette T, Taylor R, Crameri J The Royal Children’s Hospital, Melbourne, Australia, warwickteague@ gmail.com Introduction: Pathogenesis of oesophageal atresia and tracheoesophageal fistula (OA/TOF) is not clearly understood and no specific genetic factor for its aetiology was confirmed. It is supposed that combination of multigenic factors and epigenetic modification of genes can play a role in its aetiology. Results: We identified 787 down- and 841 up-regulated probes between SOA and controls, and about 817 down- and 765 up-regulated probes between IOA and controls. 50% of these genes showed DE specific for either IOA or SOA. Functional pathways analysis revealed substantial enrichment for cytokine and chemokine, Wnt and Sonic hedgehog signaling pathway. Conclusion: In-depth work on selected genes and pathways will determine if these genes may play a role in the OA/TOF etiology. We hope that these observations help to understand the pathogenesis of OA/TOF. Patients and Methods: Survival and characteristics of 493 liveborn EATEF patients were entered prospectively into an institutional database. Cases were divided into two cohorts: “historical” (1981–1996, n = 229) and “contemporary” (1997–2011, n = 264). Primary outcome was patient survival. Relative risks for survival were estimated with Cox regression; P < 0.05 significant. Results: 198/229 historical cases survived, including 30/38 VACTERL and 17/31 non-VACTERL syndromic cases; historical cohort included 7 cases trisomy 18. Of deceased cases, 5/31 had severe cardiac disease and 8/31 BW < 1500 g. 233/264 contemporary cases survived, including 51/59 VACTERL and 12/21 non-VACTERL syndromic cases; single contemporary case trisomy 18. Of deceased cases, 11/31 had severe cardiac disease and 9/31 BW < 1500 g. Non-VACTERL syndrome, VACTERL, prematurity, BW < 1500 g, but not severe cardiac disease were significantly associated with survival; see Table. Survival did not differ between cohorts. Interaction terms between cohort and syndrome were not significant, i.e. survival of syndromic EATEF was not improved in contemporary cases. Conclusions: Survival of syndromic EATEF has not improved, and nonVACTERL syndromes have the highest risk of death. Importantly, these findings are sustained if lethal syndromes are excluded, and independent of birth weight and cardiac disease. This contemporary assessment of survival will enable more accurate perinatal counseling of parents of syndromic EATEF patients. ABSTRACT 2 – oral Table POLY-ε-CAPROLACTONE MESH AS A SCAFFOLD FOR TISSUE ENGINEERING IN RABBIT OESOPHAGUS Markoew S, Frederiksen P, Le D, Hansen K, Qvist N Odense University Hospital, Odense, Denmark, Background: Long gap atresia is found in approximately 10 % of cases with oesophageal atresia where primary anastomosis is impossible. The alternative surgical procedures with gastric pull-up, intestinal interposition or secondary anastomosis after traction are associated with an increased risk of severe complications. Therefore, the development of new treatment modalities is very relevant. Tissue engineering on a scaffold of a bioresorbable material could be a solution. The aim of our study was to investigate the in vivo tissue engineering of smooth muscle cells and epithelium on a poly-εcaprolactone (PCL) mesh in rabbit oesophagus. Materials and methods: Twenty female rabbits had a window of 0.6 × 1 cm cut in the abdominal part of the oesophagus. The defect was covered with a PCL mesh. The rabbits were killed on postoperative day 28–30 and mesh with surrounding oesophagus was removed for histological examination. Results: Fifteen rabbits survived the trial period. Six had no complications and had the mesh in situ. They all had ingrowth of epithelial and smooth muscle cells and we found the mesh almost completely degraded. Nine rabbits developed pseudo-diverticula. Conclusion: It proved possible to engineer both epithelial and smooth muscle cells on the PCL mesh in spite of the fast degradation. The latter may be the explanation to the development of pseudo-diverticula; this is a problem that needs attention before further experimental trials. Variable Cohort Cardiac disease Birth weight Gestation VACTERL Non-VACTERL Adjusted analysis HR (95% CI) Historical vs Contemporary Severe vs None <1500 g vs ≥1500 g Preterm vs Term VACTERL vs None Non-lethal nonVACTERL vs None Lethal non-VACTERL vs None P value 1.00 (0.57–1.73) 0.94 1.20 2.14 2.46 2.21 5.74 (0.59–2.47) (1.05–4.34) (1.47–4.12) (1.11–4.40) (2.83–11.7) 0.61 0.04 0.001 0.02 <0.001 (27.9–211.9) <0.001 76.9 HR, Hazard Ratio (for death); CI, confidence interval ABSTRACT 4 – oral LUNG FUNCTION AND RESPIRATORY MORBIDITY IN THE FIRST YEAR OF LIFE AFTER REPAIR OF ESOPHAGEAL ATRESIA Spoel M, Gischler SJ, Hop WCJ, Tibboel D, de Jongste JCD, Wijnen RM, IJsselstijn H Department pediatric Surgery Erasmus MC – Sophia Children’s Hospital, Rotterdam, The Netherlands, Introduction: Respiratory morbidity has been described in patients who underwent repair of esophageal atresia at neonatal age. We evaluated lung function and respiratory symptoms within the first year of life in esophageal atresia patients. Patients and Methods: Functional residual capacity (FRCp), indicative of lung volume, and maximal expiratory flow at functional residual capacity (VmaxFRC), indicative of airway patency, of 37 infants operated for esophageal atresia were measured with Masterscreen Babybody at 6 and 12 months. SD-scores were calculated for VmaxFRC. Respiratory symptoms were assessed at the same time points. Results: FRCp values were in the upper normal range and increased from 6 to 12 months (22.5 and 25.4 mL/kg respectively, p = 0.010). Mean (SD) VmaxFRC was below the norm without significant change in SD-scores Methods: Total RNA was extracted from 26 esophageal tissue collected during thoracoscopic esophageal atresia repair in neonates with isolated (IOA) and syndromic form (SAO). Control tissues were taken during autopsy from aborted fetuses and stillborn neonates without OA/TOF. The study was accepted by the University Ethical Committee. We used Agilent SurePrint G3 Human GE to determined gene expression profiling in IOA and SOA vs control. Multiplicative detrending background subtraction method was performed to quantify the signal. Quality analysis and scale normalization for results were (...truncated)