Long-Term Effectiveness of Antireflux Surgery in Esophageal Atresia Patients.

INTRODUCTION: Gastroesophageal reflux disease (GERD) is a common morbidity after esophageal atresia (EA) repair, and the antireflux procedure (ARP) is a way of treating GERD symptoms. The aim of this study was to evaluate whether reflux index (Ri) and growth were improved by ARP. MATERIALS AND METHODS: Ninety-nine individuals with EA treated at the Queen Silvia Children's Hospital in Gothenburg, Sweden, between 1997 and 2010 were followed prospectively according to a structured care program. Twenty-four-hour pH-metry (Ri) and growth were studied at birth, then at 1, 7, and 15 years of age. All the patients included had reached 7 years of age. RESULTS: Preoperatively, Ri was significantly higher (32%) in the ARP than the non-ARP group (10%). Postoperatively, no difference was seen between the groups. However, at 7 and 15 years of age, Ri was significantly higher in the ARP group than in the non-ARP group. Weight (standard deviation scores) was significantly lower in the ARP group at 1 and 7 years of age when compared with the non-ARP group, but these differences were not seen at birth and at 15 years of age. In a multivariate analysis, only birth weight remained a significant factor for low weight at 7 years of age. At 15 years of age, no risk factors for low body weight were found. CONCLUSION: In the long term, ARP is not effective in reducing GERD as measured as Ri in EA patients. The ARP group had significantly lower weight at 1 and 7 years of age than the non-ARP group, but this was not the case at the age of 15.

Treatment and Follow-Up of Patients with Long-Gap Esophageal Atresia: 15 Years' of Experience from the Western Region of Sweden.

OBJECTIVE: This retrospective study aims to report treatment results in patients with long-gap esophageal atresia (LGEA), gross A + B type, and discuss the value of different clinical findings and physiological tests in the follow-up. METHODS: This retrospective observational study comprises all patients with LGEA admitted to our department between 1995 and 2010. RESULTS: A total of 16 patients were included. Their mean gestational age was 35(+2) weeks and their mean birth weight was 1,945 g (-2.5 standard deviation scores). No catch-up growth in height could be seen and they remained smaller than the average population during the study period. Gastrostomy was performed as the first surgical procedure. Overall, 11 of the 16 patients had a delayed primary anastomosis. Elongation of the distal esophageal segment was required in 3 of the 16 patients and a colonic interposition in 2 of the 16 patients. The median age at definitive surgery was 150 days. All the patients had gastroesophageal reflux after their definitive surgery. Three of the 16 patients required surgery due to aspiration and all 3 had a pathological lung clearance index (LCI) at multiple-breath washout (MBW). At the age of 1 or 7 years, the LCI was pathological in 4 of the 14 patients, and spirometry showed an obstruction in 9 of the 14 patients. CONCLUSION: LGEA is a severe congenital malformation, with severe morbidity. No mortality was seen. MBW could be a useful tool for the early detection of progressive pulmonary damage.

Physiological Studies at 7 Years of Age in Children Born with Esophageal Atresia.

OBJECTIVE: For many years, esophageal atresia (EA) has been curable by surgery. However, severe respiratory morbidity and gastroesophageal reflux (GER) symptoms remain a problem in many patients. The purpose of this study was to describe respiratory and esophageal morbidity, esophageal function, and lung function, including the small airways, in patients with the most common type of the malformation (EA with a distal fistula). METHODS: The study comprised 26 children undergoing surgery for EA, who had performed respiratory and esophageal function studies at the age of 7 years in a follow-up program. The study design was retrospective analysis of both these 7-year functional investigations and esophageal and respiratory morbidity from birth to the age of 7 years, as documented in medical records. Pulmonary function was evaluated mainly by spirometry and multiple breath washout (MBW), whereas esophageal function was evaluated by 24-hour pH studies. RESULTS: We found a high prevalence of both respiratory (69%) and esophageal (62%) morbidity between birth and 7 years among the EA children. Examination with MBW (peripheral airway function) revealed few abnormal results, whereas spirometry revealed high airway obstruction in half the children, which also correlated well with overall respiratory symptoms (p = 0.047), as well as recurrent pneumonias (p = 0.035). However, no association with GER symptoms was found. In addition, 46% of the children had GER according to pH measurements, which were correlated to clinical GER symptoms but not to respiratory symptoms. CONCLUSION: This study confirms a high prevalence of respiratory and esophageal morbidity. In terms of respiratory function, the high proportion with a spirometric abnormality indicated an associated developmental delay/dysfunction in the central airways, whereas the peripheral airways appeared to have normal function at this age. Tracheomalacia may explain the spirometric abnormalities, but this need to be studied in more detail.

Early regenerative response in the intrathoracic porcine esophagus-the impact of the inflammation.

In order to improve the treatment of children born with long-gap esophageal atresia, a porcine model was developed for studying esophageal regrowth using a bridging graft composed of a silicone stented Biodesign mesh. The aim of the study was to investigate how leakage and contact between the native muscle and Biodesign mesh affected the early healing response. Resection of 3 cm of intrathoracic esophagus was performed in 10 newly weaned piglets. They were fed through a gastrostomy 8-10 days prior to sacrifice. In order to achieve nonleaking anastomoses, the silicone stent and suturing technique had to be adjusted between the first four and second six piglets. The technical adjustment decreased leakage. A nonleaking anastomosis could not be achieved when the native muscle layers were sewn less central on the bridging graft compared with the mucosa. If there was leakage, the inflammatory response increased, with islets of perivascular T-lymphocytes and infiltration of macrophages in the native muscle layers. In the bridging area, new vessels were seen in the submucosa in 9 of 10 piglets between 4 and 10 days after surgery. Smooth muscle cells also appeared to move from the cut muscle edges of both the muscularis mucosa and the lamina muscularis and were seen as a layer of several cells under newly formed mucosa. Double staining of the basal membrane of the ingrowing vessels and the pericytes showed that the basal membrane was thinner over some of the pericytes, but there was no accumulation of immature-looking cells in the submucosa of the bridging area. In this porcine model, where esophageal regrowth was studied by using a bridging graft composed of a silicone stented Biodesign mesh, we can conclude that leakage increased the inflammatory response in early healing. Ingrowth of new vessels was seen in the bridging area and movement of smooth muscle cells was found under newly formed mucosa.

Long-term respiratory symptoms following oesophageal atresia.

BACKGROUND: Oesophageal atresia (OA) is a congenital malformation that can lead to persistent respiratory symptoms in adulthood. AIM: To describe the prevalence of respiratory symptoms in adulthood in a population-based study of patients with repaired OA and to compare this with the prevalence in the general population. METHODS: Of 80 patients operated for OA in Gothenburg in 1968-1983, 79 were located. The patients received a questionnaire on respiratory symptoms. Controls were 4979 gender- and age-matched subjects who answered the same questions. RESULTS: The questionnaire was answered by 73 of 79 (92%) patients. Physician-diagnosed asthma was reported by 30% in the OA group vs 10% in the control group (OR 4.1; 95% CI 2.4-6.8), and recurrent wheeze in 29% vs 5.5% (OR 6.9; 4.1-11.6). Also wheeze during the last year, asthma medication, a long-standing cough, cough with sputum production and chronic bronchitis were significantly more common among the patients with OA. In contrast, there was no significant difference regarding risk factors for asthma. The prevalence of respiratory symptoms did not appear to decrease with age. CONCLUSION: A high prevalence of respiratory symptoms remains among adult patients with repaired OA. Many of the patients had an asthma diagnosis. However, asthma heredity or allergic rhinitis was not overrepresented.

Incidence and survival analyses in children with solid tumours diagnosed in Sweden between 1983 and 2007.

AIM: Solid tumours constitute 40% of childhood malignancies. The Swedish Childhood Cancer Registry is population based and includes all children with cancer reported from the six paediatric oncology centres in Sweden. The aim was to investigate incidence and survival. METHODS: We used the new WHO ICCC-3 for reclassification of the patients. Incidence and survival analyses were performed in the study population. RESULTS: Two thousand four hundred and eighty-seven children (<15 years) were diagnosed with solid tumours in Sweden between 1983 and 2007. The distribution of diagnoses was similar to that reported in other studies. The annual incidence was 65.3 per million children. The survival rates at 10 years of follow-up have improved significantly when comparing the two time periods, 1983-1995 and 1995-2007 (76 vs. 82%; p < 0.01). CONCLUSIONS: The mean annual incidence of solid tumours in children was 65.3/million and has been stable during the study period. Survival rates for solid tumours at 5, 10 and 20 years follow-up were 80, 79 and 76%, respectively.

Procedure-induced inflammation and endothelial cell activation in an artificially ventilated and circulated porcine double-lung model.

Systemic inflammation is induced during extracorporeal circulation, resulting in an increased bleeding tendency and endothelial cell activation. Lungs from seven piglets were perfused by autologous blood in an extracorporeal circuit, where the lungs and the left atrium were attached to polyvinyl chloride (PVC) tubings and the blood circulated by a roller pump. The trachea was intubated and attached to a ventilator. The lungs maintained good gas exchange, despite a slight increase in lactate levels. Plasma tPA increased slightly over time, suggesting endothelial cell activation. Activation of inflammatory systems was reflected in increased levels of plasma interleukin (IL)-6 and IL-10. A model for the study of lung endothelial activation during extracorporeal circulation has been shown to be reproducible. The lung tissue was shown to be capable of gas exchange and activation of endothelial cells and procedure-induced inflammation were noted.

Congenital diaphragmatic hernia: a survey of practice in Scandinavia.

There is no consensus on the treatment of congenital diaphragmatic hernia (CDH), and practice seems to vary between centres. The main purpose of the present study was to survey current practice in Scandinavia. Thirteen paediatric surgical centres serving a population of about 22 million were invited, and all participated. One questionnaire was completed at each centre. The questionnaire evaluated management following prenatal diagnosis, intensive care strategies, operative treatment, and long-term follow-up. Survival data (1995-1998) were available from 12 of 13 centres. Following prenatal diagnosis of CDH, vaginal delivery and maternal steroids were used at eight and six centres, respectively. All centres used high-frequency oscillation ventilation (HFOV), nitric oxide (NO), and surfactant comparatively often. Five centres had extracorporeal membrane oxygenation (ECMO) facilities, and four centres transferred ECMO candidates. The majority of centres (7/9) always tried HFOV before ECMO was instituted. Surgery was performed when the neonate was clinically stable (11/13) and when no signs of pulmonary hypertension were detected by echo-Doppler (6/13). The repair was performed by laparotomy at all centres and most commonly with nonabsorbable sutures (8/13). Thoracic drain was used routinely at seven centres. Long-term follow-up at a paediatric surgical centre was uncommon (3/13). Only three centres treated more than five CDH patients per year. Comparing survival in centres treating more than five with those treating five or fewer CDH patients per year, there was a tendency towards better survival in the higher-volume centres (72.4%) than in the centres with lower volume (58.7%), p =0.065.

The effect of s-nitroso-glutathione on platelet and leukocyte function during experimental extracorporeal circulation.

Treatment with extracorporeal membrane oxygenation ECMO) is associated with side effects, e.g., blood cell consumption and activation. Our group has earlier shown that nitric oxide administered as a gas reduces platelet consumption and activation. In the present work we have studied the effect of the NO-donor S-nitroso-glutathione GSNO) on platelets and leukocytes in an in vitro extracorporeal circuit. Two complete ECMO circuits were perfused with fresh heparinized human blood for 24 hours. GSNO was administered as a continuous infusion to one circuit at a rate of 0.7 mg/hour in four paired experiments and at a rate of 3.5 mg/hour in another four paired experiments. The other circuit was used as a control. Blood samples were withdrawn from both circuits before the start of the experiments and at 0.5, 1, 3, 12, and 24 hours of perfusion. The samples were analyzed for red blood cell count, leukocyte count, platelet count, platelet membrane expression of glycoproteins GP) Ib and GPIIb/IIIa, leukocyte membrane expression of cluster of differentiation CD) 11b/CD18, as well as plasma concentration of tumor necrosis factor TNF)-alpha, interleukin IL)-1beta, and IL-8. No difference in these parameters between the GSNO and the control circuit at any time point was assayed. In this study, no significant effect of GSNO on circulating platelets or leukocytes during experimental extracorporeal circulation could be shown.

Congenital diaphragmatic hernia in Scandinavia from 1995 to 1998: Predictors of mortality.

BACKGROUND/PURPOSE: There is a lack of large contemporary studies on the management of congenital diaphragmatic hernia (CDH), and the prediction of mortality remains difficult. The aim of this study was to investigate the influence of perinatal factors on mortality rate in a contemporary multicenter study. METHODS: The authors conducted a retrospective multicenter cohort study. Twelve of 13 Scandinavian pediatric surgical centers participated in the study. During a 4-year period (1995 through 1998) 195 children with CDH were included. The main endpoints were hospital mortality rate and total mortality rate (before 2001). Bivariate and multivariate survival analyses were performed using Kaplan-Meier plots, Log-rank test, and Cox regression. RESULTS: Overall hospital mortality rate was 30%. Among 168 neonates with symptoms within 24 hours (early presenters) 35% died before discharge. All 61 deaths occurred in 157 neonates with symptoms within the first 2 hours of life. Among early presenters, 27% had prenatal ultrasound diagnosis, 26% were delivered by cesarean section, and 21% had associated major malformations. Bivariate analysis of early presenters showed increased risk of death in neonates with prenatal diagnosis, associated anomalies, right-sided diaphragmatic hernia (RCDH), low 1-minute and 5-minute Apgar scores, low birth weight, short gestational age, and cesarean delivery. Neonates with prenatal diagnosis were characterized by significantly lower Apgar scores, lower birth weight, and increased frequency of associated anomalies than those diagnosed after birth. Multivariate analysis found that prenatal diagnosis (P =.004), 1-minute Apgar (P =.001), and RCDH (P =.042) were independent predictors of total mortality rate. CONCLUSIONS: In a series of 195 CDH patients, all 61 deaths occurred in the 157 neonates presenting with symptoms within the first 2 hours of life. Prenatal diagnosis, 1-minute Apgar score, and RCDH were significant independent predictors of total mortality.