Oesophageal atresia is correctable and survivable in infants less than 1 kg.

INTRODUCTION: Management of oesophageal atresia (OA) and trachea-oesophageal fistula (TOF) in babies of low birth weight is challenging especially when associated with other anomalies. Birth weight of <1500 g has previously formed part of a classification system designed to predict outcome, alongside the cardiac status of the patient. Improvements in neonatal care have led to increasing numbers of premature low birth weight infants surviving. The aim of this study was to look at the experience of our institution in the extremely low birth weight (ELBW) patients. METHODS: A retrospective review of our institutions OA database was performed from 1993 to June 2015. Patients of birth weight less than 1000 g were included. A review of our OA/TOF clinical database and notes review established the following; gestation, birth weight, associated anomalies, operative procedures, morbidity and mortality. RESULTS: Of 349 patients with OA across the 22-year period, 9 ELBW patients were identified (<1000 g). Six males and three females. Gestational age ranged from 23 to 34 weeks and median birth weight was 815 g ranging from 630 to 950 g. Overall survival was 56 % (5/9). There were double the numbers of ELBW OA/TOF patients seen in the second half of the study period presumably the result of improving neonatal care. Seven patients had type C OA with TOF and underwent emergency TOF ligation, two had concomitant oesophageal repair. One of these patients died from NEC; the other survived. Of the five who had isolated TOF ligation three died-two from cardiac disease and one from prematurity. Both type A patients survived and after initial gastrostomy placement one had a primary delayed repair, the other a gastric transposition. All three babies under 800 g died-one from cardiac disease the others from conditions indicative of their prematurity-necrotising enterocolitis and intraventricular haemorrhage. CONCLUSIONS: 50 % survival is achievable in OA/TOF under 1 kg and the Spitz classification is still applicable in this group as a whole. However, none of the current classification systems are applicable in infants <800 g who in our study all had poor outcomes. We suggest these should be considered as separate group when predicting outcomes.

Foregut separation and tracheo-oesophageal malformations: the role of tracheal outgrowth, dorso-ventral patterning and programmed cell death.

Foregut division-the separation of dorsal (oesophageal) from ventral (tracheal) foregut components-is a crucial event in gastro-respiratory development, and frequently disturbed in clinical birth defects. Here, we examined three outstanding questions of foregut morphogenesis. The origin of the trachea is suggested to result either from respiratory outgrowth or progressive septation of the foregut tube. We found normal foregut lengthening despite failure of tracheo-oesophageal separation in Adriamycin-treated embryos, whereas active septation was observed only in normal foregut morphogenesis, indicating a primary role for septation. Dorso-ventral patterning of Nkx2.1 (ventral) and Sox2 (dorsal) expression is proposed to be critical for tracheo-oesophageal separation. However, normal dorso-ventral patterning of Nkx2.1 and Sox2 expression occurred in Adriamycin-treated embryos with defective foregut separation. In contrast, Shh expression shifts dynamically, ventral-to-dorsal, solely during normal morphogenesis, particularly implicating Shh in foregut morphogenesis. Dying cells localise to the fusing foregut epithelial ridges, with disturbance of this apoptotic pattern in Adriamycin, Shh and Nkx2.1 models. Strikingly, however, genetic suppression of apoptosis in the Apaf1 mutant did not prevent foregut separation, indicating that apoptosis is not required for tracheo-oesophageal morphogenesis. Epithelial remodelling during septation may cause loss of cell-cell or cell-matrix interactions, resulting in apoptosis (anoikis) as a secondary consequence.

Outcomes in adulthood of gastric transposition for complex and long gap esophageal atresia.

BACKGROUND: Long term outcomes of gastric transposition (GT) for complex esophageal atresia (EA) are poorly reported. We aimed to perform comprehensive long term follow up of adults who had been treated with GT for EA as children. METHODS: Consecutive patients who underwent GT for EA in childhood aged >18 years old were identified alongside age matched patients who had primary repair (PR). Type of EA, comorbidities and details of surgery were recorded. Telephone interviews included medical history, current symptoms - including gastrointestinal symptom rating scale (GSRS), morbidity and health related quality of life (HRQoL) using gastrointestinal quality of life index (GIQLI). RESULTS: 32 participants were interviewed in each group (mean age 29 years). BMI (19.9 ±â€¯3.5) was significantly lower (p = 0.0006) in GT group. 6/32 (19%) still required supplementary feeding. Adult morbidity included anastomotic stricture (34%), chronic respiratory disease (28%), dumping symptoms (25%), anemia (47%) and depression (19%). 3 patients required major revision surgery. Participants in both groups report regular upper gastrointestinal symptoms (GSRS: GT = 2.1, PR = 2.0) and were more symptomatic than the normal population (1.4) but not statistically different from each other. HRQoL (GIQLI = 113) was lower than after PR (122) but not significantly different (p = 0.29) and the normal population (125). 23% of GT participants had higher than normal HRQoL. CONCLUSIONS: GT for EA is associated with significant morbidity and symptoms, including issues previously unreported in adulthood such as mental health problems. This mandates long term follow up and quality transition of these patients into adult care. TYPE OF STUDY: Retrospective study. LEVEL OF EVIDENCE: Level III.

Gastric transposition in children.

PURPOSE: To analyze the outcome in 192 children (116 males, 76 females) undergoing transposition since 1981. METHODS: The most common indications for esophageal replacement included failed repair of different varieties of esophageal atresia (138), caustic injury (29), and peptic strictures (9). A total of 81% of the patients were referred from other hospitals (50% from other countries). Age at operation ranged from 7 days to 17 years. The gastric transposition was performed by using blunt mediastinal dissection in 98 patients, with an additional 90 patients undergoing lateral thoracotomy. The retrosternal position was used in 4 patients. RESULTS: There were no graft failures, including those who had previously had failed gastric tube or Scharli operations. Anastomotic leaks occurred in 12% (all but one resolved spontaneously). Anastomotic stricture, requiring dilation developed in 20%. Half of these patients had previously sustained caustic esophageal injury. There were 9 deaths in the group (4.6%). One death occurred intraoperatively, 5 in the early postoperative period, and there were 3 late deaths. In over 90% of our patients, the outcome was considered good to excellent in terms of absence of swallowing difficulties or other gastrointestinal symptoms. Many children preferred to eat small frequent meals. Poor outcome was particularly associated with multiple previous attempts at esophageal salvage. There was no deterioration in the function of the gastric transposition in those patients followed for more than 10 years. CONCLUSIONS: Gastric transposition for esophageal substitution is an acceptable procedure. It is attended by 4.6% mortality and a 12% leak rate. A total of 20% of the patients needed anastomotic dilation for stricture. In the long term, good function has been maintained. Gastric transposition compares favorably with other methods of esophageal replacement.

Esophageal Atresia: Improved Outcome in High-Risk Groups Revisited.

Objectives Improved survival in infants with esophageal atresia (EA) with a birth weight < 1,500 g or a major cardiac anomaly has been reported when compared with the original Spitz classification proposed in 1994. Aim We reviewed outcome data for infants born over the last decade in our institution to update previously reported survival statistics. Materials and Methods The records of all neonates (n = 200) with a diagnosis of EA managed in a single institution between 2001 and 2011 were reviewed and compared with data from the original Spitz study and the subsequent reported cohort from the same institution. Data were obtained on birth weight, presence of a major cardiac anomaly, and survival. Differences in survival were compared using the Yates-corrected chi-square test. Local ethical study approval was obtained. Results Infants born over the last decade had a comparable overall survival rate of 93% (186/200) versus 92.6% (174/188) in the previously reported cohort (1993-2004). We demonstrate an improved survival as compared to the Spitz cohort (87.6%, 326 /372, p = 0.06) and a statistically significant improvement in survival in Group II (p = 0.01). Within this group, 12/51 neonates had a birth weight < 1,500 g and 39/51 had major cardiac anomalies. Of interest, of the nine deaths in Group II, eight were in the subgroup with major cardiac anomalies. Conclusion The survival of neonates in Group II has significantly improved. Mortalities within this group were predominantly in the subgroup with major cardiac anomalies suggesting birth weight is of less significance than in previous years reflecting recent advances in neonatal care. We propose an updated prognostic classification that makes a distinction between cardiac and low-birth-weight infants.

Tyrosine nitration of carnitine palmitoyl transferase I during endotoxaemia in suckling rats.

Heart carnitine palmitoyl transferase I (CPTI) is inhibited in vivo during endotoxaemia and in vitro by peroxynitrite but the biochemical basis of this inhibition is not known. The aim of this study was to determine which isoform of CPT I is inhibited during endotoxaemia and whether the inhibition is due to increased tyrosine nitration. Cardiac mitochondria were isolated from endotoxaemic suckling rats. To determine whether M- or L-CPTI was inhibited, we carried out titrations with DNP-etomoxir-CoA. Slopes of the titration curves with DNP-etomoxir-CoA were no different between control and endotoxaemia, suggesting that M-CPTI was specifically inhibited. Immunoprecipitation was carried out using an anti-nitrotyrosine antibody. Immunoprecipitated proteins were identified by Western blotting with L- and M-CPTI specific antibodies. L-CPTI was nitrated both in control and in 2- and 6-h endotoxaemia mitochondria but there was no significant difference in the level of nitration. M-CPTI was also nitrated in control mitochondria but nitration was significantly increased at both 2- and 6-h endotoxaemia. Either 10 mM 3-nitrotyrosine plus 40 microg nitrated-albumin or 0.5 M dithionite, during immunoprecipitation, greatly decreased immunopositivity for M- and L-CPTI on WB. M-CPTI appears to be a novel target for peroxynitrite during endotoxaemia, which would alter myocardial substrate selection.

Moderate hypothermia protects against systemic oxidative stress in a rat model of intestinal ischemia and reperfusion injury.

Multisystem organ failure represents a major cause of mortality in intestinal ischemia and reperfusion (I/R), and oxidative stress plays a key role in its pathogenesis. Hypothermia is beneficial in I/R injury, but its effects on systemic oxidative stress have not been elucidated. The aim of this study was to evaluate the effects of moderate hypothermia on systemic oxidative stress after intestinal I/R injury. Anaesthetized adult rats (n = 10 per group) underwent 60 min of intestinal ischemia followed by 120 min of reperfusion or sham operation at normothermia (36 degrees C-38 degrees C) or moderate hypothermia (30 degrees C-32 degrees C). At sacrifice, ileum, liver, lungs, and kidneys were removed to determine the concentration of malondialdehyde (a marker of lipid peroxidation), reduced and oxidized glutathione (a major endogenous antioxidant), and glutathione redox state. Plasma malondialdehyde and nitrate plus nitrite (reflecting nitric oxide production) were also analyzed. A marked elevation of malondialdehyde was observed after I/R at normothermia in plasma, ileum, and lungs; however, hypothermia during I/R prevented this increase. I/R at normothermia caused a profound decrease in reduced glutathione and glutathione redox state in the ileum, but this was not observed in I/R at hypothermia. Interestingly, hypothermia increased glutathione content of control intestine. Nitric oxide production was increased only in normothermic I/R animals. Moderate hypothermia attenuates systemic oxidative stress associated with experimental intestinal I/R in an animal model by decreasing lipid peroxidation in plasma, ileum, lungs, and kidneys, by preventing the depletion of gut glutathione, and by reducing systemic nitric oxide production. However, whether these effects persist after rewarming is unknown.

Ethics in the management of conjoined twins.

In dealing with conjoined twins, we have adopted a pragmatic approach in balancing what is possible, parental wishes and the likely outcome for the children. We believe that separation where feasible should be undertaken but appreciate that a few parents may wish their children to remain joined. The advice that we give balances the very real risks of surgery against the type of life the twins will experience if they remain joined. In some types of union such as end to end ischiopagus, the twins will never stand and will be bedridden. With other types of union, independent walking is not possible. Such limitations on living seem intolerable to us, but we have left the final decision to parents.

Planning the operation.

The management of conjoined twins falls into three distinct groups-non-operative, emergency separation and elective separation. Planning meetings involving all the personnel who will be required during the operation are held. The radiological findings are presented and the anaesthetic, nursing and intensive care requirements are highlighted.

The separation procedure.

The various stages of the separation are carefully planned but despite this, variations which will change the schedule of the procedure may exist. In general the operation commences on the opposite side from the main procedure and then the twins are turned for the remainder of the operation. Each type of conjoined twin is different but basically thoracopagus involves the hearts, omphalopagus involves the liver and small intestine and ischiopagus involves the large intestine and genito-urinary system. Our results are presented together with interesting cases from which lessons have been learned.

Classification and clinical evaluation.

Conjoined twins represent a great challenge for most pediatric specialists including pediatric surgeons, anesthetists, neonatologists, urologists, neurosurgeons, and orthopedic surgeons. This anomaly can be classified according to the type of twins׳ fusion. Various organs can be fused making the separation difficult. Conjoined twins are usually diagnosed antenatally by ultrasound. Detailed fetal echocardiography is necessary to counsel the parents during pregnancy. Postnatally, the majority of the conjoined twins can be thoroughly investigated using various imaging techniques. This allows careful planning of the operation. However, in approximately one-third of the patients an urgent operation is required at birth without a complete assessment of the joining. This is associated with a poorer outcome.

Theatre setup.

The theatre staff would have been made aware of the special requirements for the operation at the planning meetings. Two sets of scrubs nurses will be required but only one set will be needed for the actual separation. The second set of scrub nurses will be needed only when both twins have survived the separation and the second twin is moved to another operating room for closure of the wound.

Is intralesional injection of OK-432 effective in the treatment of lymphangioma in children?

BACKGROUND: Intralesional injection of OK-432 has been proposed as an effective treatment of lymphangioma. The aim of this study was to review our experience with OK-432 injection of lymphangioma and to identify factors associated with successful outcome. METHODS: We made a case note review of 19 children who received OK-432 injection. Median duration of follow-up was 17 months. RESULTS: Lesions were diagnosed antenatally in 4 children, at birth in 4 children, and between 1 month and 11 years in the remainder. Anatomic locations were head/neck in 14, axilla in 1, and multiple locations in 4. Median number of injections per child was 2 (range, 1 to 5). Disappearance of the lesion was achieved after OK-432 injection in 2 patients (11%) and a marked reduction in 5 (26%); all these lesions were in the head and neck. Lesions larger than 5 cm and those outside the head and neck region did not respond well to OK-432 injection. Fourteen children (74%) required surgical excision after injection. Complications of OK-432 injection included partial tracheal obstruction, fever, local inflammatory response, and abscess formation. CONCLUSIONS: OK-432 injection was effective in approximately one third of children with lymphangioma. Lesions outside the head and neck and those larger than 5 cm are unlikely to respond to this therapy. Injection of lymphangioma surrounding the airways may be hazardous.

Fatty acid oxidation in neonatal hepatocytes: effects of sepsis and glutamine.

OBJECTIVE: Little is known about fat use during sepsis during the neonatal period. Intramitochondrial O(2) consumption is inhibited in isolated hepatocytes from suckling septic rats and this impairment is reversed by glutamine. We investigated the effect of neonatal sepsis on fat oxidation and whether glutamine can directly affect fatty acid oxidation. METHODS: Suckling Wistar rats (11 d) received an intraperitoneal injection of 300 microg/kg of lipopolysaccharide (Escherichia coli 055:B5); controls received normal saline. At 2 h, hepatocytes were isolated. Hepatocytes were incubated at 37 degrees C with 0.5 mM [1-(14)C]palmitate or 0.5 mM [1-(14)C]palmitate plus 10 mM glutamine. After 1 h, the perchloric acid-soluble (14)C-radioactivity (representing mainly ketone bodies) and (14)CO(2) were measured. Hepatocyte O(2) consumption from 0.5 mM palmitate was measured with and without 2.5 ng/mL myxothiazol to estimate intramitochondrial O(2) consumption. RESULTS: There were no significant differences in fatty acid oxidation between control and endotoxemic hepatocytes measured as acid-soluble radioactivity (which represents mainly ketogenesis, plus Krebs cycle intermediates), as (14)CO(2) production, or as the sum of acid-soluble radioactivity plus (14)CO(2) generation. Glutamine significantly increased fatty acid oxidation (acid-soluble radioactivity plus (14)CO(2)) in hepatocytes from control and endotoxic animals. CONCLUSIONS: The finding of no significant difference in fatty acid oxidation between hepatocytes from control and endotoxemic rats is surprising given that intramitochondrial O(2) consumption from palmitate is decreased. This may reflect altered use of acetyl-coenzyme A to ketone bodies and Krebs cycle intermediates. Glutamine enhanced fatty acid oxidation from control and endotoxemic hepatocytes, suggesting that it may promote substrate oxidation during endotoxemia.

Hepatic glutamine metabolism during endotoxemia in neonatal rats.

OBJECTIVES: The liver plays a central role during endotoxemia. We investigated the biochemical changes that occur in neonatal liver during early stages of endotoxemia. METHODS: Twenty neonatal rats (10 to 15 d; n = 10/group) were studied. Endotoxemic rats received intraperitoneal injections of 300 microg/kg of 12.5 mg/L of lipopolysaccharide and control rats received isovolemic normal saline. Two hours after injection, all lipopolysaccharide-injected animals exhibited signs of endotoxemia. Livers were removed and extracted into 12% perchloric acid. 1H and 31P magnetic resonance spectroscopy measured hepatic levels of glutamine, glutamate, alanine, lactate, glucose, beta-hydroxybutyrate, adenosine triphosphate, and adenosine diphosphate. Unpaired t test compared groups. RESULTS: No mortality occurred during the first 2 h after injection. Endotoxemia significantly decreased hepatic levels of glutamine (P < 0.001), glucose (P = 0.047), and beta-hydroxybutyrate (P < 0.001). There was no difference in hepatic levels of glutamate (P = 0.050), alanine (P = 0.165), lactate (P = 0.478), adenosine triphosphate (P = 0.165), and adenosine diphosphate (P = 0.136) between groups. CONCLUSIONS: Early endotoxemia caused significant changes in the hepatic metabolism of glutamine, glucose, and beta-hydroxybutyrate. These findings increase our understanding of the pathophysiology of neonatal endotoxemia.

Effects of early hospitalization and surgery on the emotional development of 3 year olds: An exploratory study.

The emotional and social development of full term infants who required major neonatal surgery were compared prospectively over 3 years with those of a matched group of healthy infants. Ratings of the mother-child relationship and attachment ratings at 12 months indicated that in the short-term there was no evidence of any adverse effects of early hospitalization. At 3 years of age however, the children in the surgical group as a whole showed an increased incidence of behaviour problems, and there was a higher rate of difficulties in the mother-child relationship compared with the controls. Within the surgical group, a combination of a lengthy first admission, repeat admissions, and family and social factors were associated with this increased rate of emotional and behavioural difficulties.

Esophageal replacement: overcoming the need.

Three developments which have contributed to the declining necessity for esophageal replacement are improvement in the management of esophageal atresia, prevention of caustic injuries to the esophagus, and early antireflux surgery for intractable gastro-esophageal reflux. Despite these advances, replacement of the esophagus may still be necessary. The two most commonly used procedures for replacing the esophagus are colonic interposition and gastric transposition. Experience with 236 gastric transposition operations reveals a mortality of 2.5%, leak rate of 12%, and stricture of 20%. The follow-up shows a satisfaction of over 90%. New methods of overcoming the need for esophageal replacement are in progress with tissue engineering with a scaffold to produce a tubular graft to bridge the gap in the continuity of the esophagus.

The history of paediatric surgery in the United Kingdom and the influence of the national health service on its development.

Details of the modern history of paediatric surgery in the United Kingdom with particular emphasis on the 3 main training centres in England in the 1960s to 1970s are discussed. The genesis of the National Health Service and of the British Association of Paediatric Surgeons and their influence on the establishment and sitting of regional centres, education and training, and centralization of rare conditions is highlighted.

Duhamel pull-through for Hirschsprung disease: a comparison of open and laparoscopic techniques.

PURPOSE: Various pull-through techniques, both open and laparoscopic, have been performed for Hirschsprung disease. Our study compares open and laparoscopic Duhamel pull-through. METHODS: After ethical approval, we reviewed all children (n = 181) with Hirschsprung disease admitted to our institution between 1999 and 2009. We excluded total colonic aganglionosis (n = 14), previous pull-through done elsewhere (n = 33), or follow-up performed abroad (n = 58). Open and laparoscopic pull-through were done in the same period according to surgeon preference. Data were analyzed using χ(2) or Mann-Whitney U test. RESULTS: Seventy-six children had a Duhamel pull-through for rectosigmoid aganglionosis. Operative time, time to full feeds, and length of hospital stay were similar in each group. OPEN (N = 41): Fifteen children (37%) required 33 further procedures. Fourteen had procedures for persistent constipation, including redo Duhamel (n = 2), stoma formation (n = 2), spur division (n = 2), and dilatation/stretch/Botox/rectal biopsy/manual evacuation (n = 23). Three children had other procedures (adhesiolysis [n = 2] and incisional hernia repair [n = 1]). LAPAROSCOPIC (N = 35): Fourteen children (40%) required 30 further procedures. Eleven had procedures for persistent constipation, including redo Duhamel (n = 1), stoma formation (n = 4), spur division (n = 9), and dilatation/stretch/rectal biopsy (n = 8). Three children had other procedures (adhesiolysis [n = 1] and incisional hernia repair [n = 2]). There were 4 conversions. CONCLUSION: Open and laparoscopic Duhamel pull-through have similar outcomes. We show that the techniques have comparable operative times and hospital stay.