Butyrate enemas enhance both cholinergic and nitrergic phenotype of myenteric neurons and neuromuscular transmission in newborn rat colon.

Postnatal changes in the enteric nervous system (ENS) are involved in the establishment of colonic motility. In adult rats, butyrate induced neuroplastic changes in the ENS, leading to enhanced colonic motility. Whether butyrate can induce similar changes during the postnatal period remains unknown. Enemas (Na-butyrate) were performed daily in rat pups between postnatal day (PND) 7 and PND 17. Effects of butyrate were evaluated on morphological and histological parameters in the distal colon at PND 21. The neurochemical phenotype of colonic submucosal and myenteric neurons was analyzed using antibodies against Hu, choline acetyltransferase (ChAT), and neuronal nitric oxide synthase (nNOS). Colonic motility and neuromuscular transmission was assessed in vivo and ex vivo. Butyrate (2.5 mM) enemas had no impact on pup growth and histological parameters compared with control. Butyrate did not modify the number of Hu-immunoreactive (IR) neurons per ganglia. A significant increase in the proportion (per Hu-IR neurons) of nNOS-IR myenteric and submucosal neurons and ChAT-IR myenteric neurons was observed in the distal colon after butyrate enemas compared with control. In addition, butyrate induced a significant increase in both nitrergic and cholinergic components of the neuromuscular transmission compared with control. Finally, butyrate increased distal colonic transit time compared with control. We concluded that butyrate enemas induced neuroplastic changes in myenteric and submucosal neurons, leading to changes in gastrointestinal functions. Our results support exploration of butyrate as potential therapy for motility disorders in preterm infants with delayed maturation of the ENS.

Early surgical complications after congenital diaphragmatic hernia repair by thoracotomy vs. laparotomy: A bicentric comparison.

PURPOSE: The surgical strategy for congenital diaphragmatic hernia (CDH) repair remains debated and mainly depends on the training and preference of the surgeon. Our aim was to evaluate the occurrence and nature of surgical reinterventions within the first year of life, following repair through thoracotomy as compared to laparotomy. METHODS: This is a retrospective bi-centric cohort study comparing postero-lateral thoracotomy (n = 55) versus subcostal laparotomy (n = 62) for CDH repair (IRB: MP001882). We included neonates with isolated, left-sided, Bochdalek-type CDH who were operated on between 2000 and 2017, and had a minimum follow-up of 1 year. Excluded were patients treated prenatally and/or had extra-corporeal membrane oxygenation. Outcomes were occurrence and nature of surgical reinterventions and mortality by 1 year of life. RESULTS: Both groups had comparable neonatal severity risk profiles. The overall surgical reintervention rate by 1 year of age was higher in the thoracotomy group (29.1% vs. 6.5%; p = 0.001), mainly because of a higher prevalence of acute bowel complications (18.1% vs. 3.2%; p = 0.012) requiring surgery, such as perforation, obstruction and volvulus. At 1 year of follow-up, groups were similar in terms of recurrence (5.5% vs. 1.6%; p = 0.341), surgical interventions related to severe gastroesophageal reflux disease (3.6% vs. 1.6%; p = 0.600) and mortality (5.5% vs. 6.6%; p = 1.000). CONCLUSION: Postnatal CDH repair through thoracotomy was associated with a higher rate of surgical reinterventions within the first year of life, especially for severe acute gastro-intestinal complications. There seemed to be no difference in recurrence and mortality rate. TYPE OF STUDY: Retrospective Comparative Cohort Study. LEVEL OF EVIDENCE: Level III.

Patch repair of congenital diaphragmatic hernia is not at risk of poor outcomes.

PURPOSE: Recurrence of congenital diaphragmatic hernia (CDH) was retrospectively evaluated after correction with or without a patch in an institution where tension-free repair is advocated. METHODS: Demographics and outcomes of patients with a postero-lateral CDH repaired (2000-2016) were analyzed (univariate tests and binary logistic regression adjusting for time since start of study, gender, defect side, liver herniation, patch, surgical approach, absence of postero-lateral rim and length of follow-up). RESULTS: Of 203 patients, 107 received a patch (P), and 96 were not patched (NP). Groups were not different for gestational age birthweight, gender, defect side and minimally invasive approach rate. Preoperative ECMO incidence (P:29.9% vs. NP:2.1%, p < 0.01), liver herniation (P:57.0% vs. NP:22.9%, p < 0.01) and absence of a postero-lateral rim (P:61.7% vs. NP:8.3%, p < 0.01) were higher in the P group. The mortality rate was 10.8% (P:15.0% vs. NP:6.2%, p = 0.07). Recurrence was not different (P:9.3% vs. NP:4.2%, p = 0.15). Multivariate analysis showed that recurrence was higher after thoracoscopy compared to open (OR = 12.2 [2.2-68], p < 0.01); neither the use of patch (OR = 2.3, [0.5-10.4], p = 0.28) nor any other factors were associated with recurrence. CONCLUSION: In this single centre series where tension-free repair was advocated, patch repair of CDH was not associated with higher recurrence, though access route was. TYPE OF STUDY: Cohort Study. LEVEL OF EVIDENCE: Level III.

Analysis of enteric nervous system and intestinal epithelial barrier to predict complications in Hirschsprung's disease.

In Hirschsprung's disease (HSCR), postoperative course remains unpredictable. Our aim was to define predictive factors of the main postoperative complications: obstructive symptoms (OS) and Hirschsprung-associated enterocolitis (HAEC). In this prospective multicentre cohort study, samples of resected bowel were collected at time of surgery in 18 neonates with short-segment HSCR in tertiary care hospitals. OS and HAEC were noted during postoperative follow-up. We assessed the enteric nervous system and the intestinal epithelial barrier (IEB) in ganglionic segments by combining immunohistochemical, proteomic and transcriptomic approaches, with functional ex vivo analysis of motility and para/transcellular permeability. Ten HSCR patients presented postoperative complications (median follow-up 23.5 months): 6 OS, 4 HAEC (2 with OS), 2 diarrhoea (without OS/HAEC). Immunohistochemical analysis showed a significant 41% and 60% decrease in median number of nNOS-IR myenteric neurons per ganglion in HSCR with OS as compared to HSCR with HAEC/diarrhoea (without OS) and HSCR without complications (p = 0.0095; p = 0.002, respectively). Paracellular and transcellular permeability was significantly increased in HSCR with HAEC as compared to HSCR with OS/diarrhoea without HAEC (p = 0.016; p = 0.009) and HSCR without complications (p = 0.029; p = 0.017). This pilot study supports the hypothesis that modulating neuronal phenotype and enhancing IEB permeability may treat or prevent postoperative complications in HSCR.

Laparoscopic Ladd's procedure for malrotation in infants and children is still a controversial approach.

BACKGROUND: Open Ladd's procedure is the gold standard for the correction of intestinal malrotation and laparoscopic approach remains controversial. This study aimed to evaluate our experience in laparoscopic management of malrotation. METHODS: Single center retrospective study including patients who underwent a laparoscopic assessment of intestinal malrotation with correction if appropriate between 2007 and 2017. RESULTS: Sixty-five patients (median age 7 months) had a laparoscopic assessment with and without correction of malrotation. Forty-five (69%) were symptomatic, including 16 (25%) with a midgut volvulus. The procedure was completed laparoscopically in 55 (86%) patients in 110 min (30-190). Conversions happened more frequently at the beginning of the experience. With a follow-up of 12.5 months (8 days-5.3 years), morbidity rate was 15% and 4 (6%) patients underwent a redo surgery, all in the first 5 months after surgery, compared with 3/53 (6%) in a contemporaneous group undergoing open Ladd's. CONCLUSION: This is the largest series reported so far of the laparoscopic management of malrotation. Laparoscopic Ladd's procedure is reliable but still exposes to open conversion which may be in part owing to a learning curve. A low conversion threshold is important in cases with volvulus. The redo rate is similar to that of the open procedure. LEVEL OF EVIDENCE: Level III retrospective comparative treatment study.

Spontaneous Intestinal Perforation and Necrotizing Enterocolitis: A 16-Year Retrospective Study from a Single Center.

BACKGROUND: Necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP) are serious abdominal conditions that affect preterm infants but are poorly understood. This single-center retrospective study was performed to identify the factors associated with NEC and SIP. METHODS: This study involved 3,464 preterm infants recruited over 16 years. A total of 136 NEC and 24 SIP were analyzed and adjusted odds ratios (aOR) were determined by logistic regression. RESULTS: Compared with the controls, NEC was associated with a Z-score for birth weight lower than -1 (aOR = 2.1 [1.1-3.9], p = 0.02) and lower than -2 (aOR = 4.4 [1.8-10.4], p < 0.01). NEC was associated with gestational ages of less than 31 weeks and with breech presentations (aOR = 1.5 [1.0-2.3], p = 0.03). In contrast, compared with the controls, SIP was associated with gestational ages of less than 26 weeks (aOR = 17.4 [3.1-96.2], p < 0.001) and multiple pregnancy (aOR = 2.9 [1.2-6.9], p = 0.02). Rates of mortality and cerebral lesions were higher in patients with NEC (25.0 and 13.2%, respectively) than with the controls (10.1 and 6.9%, respectively) and similar between patients with SIP (12.5 and 8.3%, respectively) and the controls. CONCLUSIon: NEC and SIP differed in risk factors and prognosis. Early distinction of SIP from NEC could impact on surgical decision.

Retroperitoneal laparoscopic heminephrectomy in duplex kidney in infants and children: a 15-year experience.

BACKGROUND: Laparoscopic retroperitoneal partial nephrectomy in children remains a complex technique with limited diffusion among the paediatric surgical community. OBJECTIVE: To report our experience with laparoscopic heminephrectomy in duplex kidneys after a 15-yr practise of the technique in children and infants. DESIGN, SETTING, PARTICIPANTS: Forty-eight children with retroperitoneal laparoscopic partial nephrectomy (36 upper-pole nephrectomies [UPN] and 12 lower-pole nephrectomies [LPN]) were retrospectively included in this single-institution study. Median age at surgery was 8.6 mo (range 1.5-89), with a policy of early surgical intervention for UPN in cases involving a massively dilated upper tract. INTERVENTION: Retroperitoneal laparoscopic partial nephrectomy for duplex kidney in lateral position (n=31) and prone in the last 17 cases. MEASUREMENTS: We assessed intraoperative and postoperative morbidity. Follow-up (median 14 mo, range 6-125 mo) was based on clinical review and renal ultrasound. RESULTS AND LIMITATIONS: Median duration of surgery was 120 min (range 71-215). Ten procedures (21%) were converted into open surgery, mostly at the beginning of the experience (eight during the first 20 cases, as compared to one conversion in the last 20). Among four converted LPNs, three were converted for difficulties during parenchymal section. Six UPN were converted for difficulties of exposure, with a strong correlation with age: all six were infants, with a median age of 3.25 mo (range 1.5-8 mo). We observed one case (case 4) of functional loss of the remaining lower moiety. CONCLUSIONS: This study shows a high conversion rate during the learning curve for laparoscopic heminephrectomy. Retroperitoneoscopic UPN remains a challenging procedure in children, especially in small infants with very dilated collecting systems. The possibility of vascular damage to the remaining moiety warrants a very cautious dissection of the renal pedicle and should lead to conversion when clear visualization of vascular anatomy is not ascertained.