Sequence variants identification at the KCNQ1OT1:TSS differentially Methylated region in isolated omphalocele cases.

BACKGROUND: Omphalocele is a congenital midline ventral body wall defect that can exist as isolated malformation or as part of a syndrome. It can be considered one of the major and most frequent clinical manifestation of Beckwith-Wiedemann Syndrome (BWS) in case of loss of methylation at KCNQ1OT1: Transcription Star Site-Differentially Methylated Region (TSS-DMR) or in presence of CDKN1C mutations. The isolated form of the omphalocele accounts approximately for about the 14% of the total cases and its molecular etiology has never been fully elucidated. METHODS: Given the tight relationship with BWS, we hypothesized that the isolated form of the omphalocele could belong to the heterogeneous spectrum of the BWS associated features, representing an endophenotype with a clear genetic connection. We therefore investigated genetic and epigenetic changes affecting BWS imprinted locus at 11p15.5 imprinted region, focusing in particular on the KCNQ1OT1:TSS DMR. RESULTS: We studied 21 cases of isolated omphalocele detected during pregnancy or at birth and identified the following rare maternally inherited variants: i) the non-coding variant G > A at nucleotide 687 (NR_002728.3) at KCNQ1OT1:TSS-DMR, which alters the methylation pattern of the imprinted allele, in one patient; ii) the deletion c.624-629delGGCCCC at exon 1 of CDKN1C, with unknown clinical significance, in two unrelated cases. CONCLUSIONS: Taken together, these findings suggest that KCNQ1OT1:TSS-DMR could be a susceptibility locus for the isolated omphalocele.

Classification and management of rectal prolapse after anorectoplasty for anorectal malformations.

PURPOSE: To suggest a classification, describe the risk factors and management of rectal prolapse after anorectoplasty for anorectal malformations (ARMs). METHODS: We classified prolapse as minimal (rectal mucosa visible with Valsalva manoeuvre), moderate (prolapse <5 mm without Valsalva), evident (>5 mm without Valsalva) and compared patients with and without prolapse within our ARM-population. RESULTS: Among 150 patients, 40 (27 %) developed prolapse: 25 minimal, 6 moderate, 9 evident. Prolapse affected 33 % of males (9 % of perineal fistulas, 38 % of bulbar, 71 % of prostatic, 60 % of bladder neck and 13 % without fistula) and 21 % of females (9 % of perineal, 30 % of vestibular, 50 % of cloacas, and 25 % without fistula). Risk factors for prolapse were: tethered cord (40 vs 24 %), vertebral anomalies (39 vs 24 %), laparoscopic-assisted anorectoplasty (LAARP) (75 vs 25 %), and colostomy at birth (49 vs 9 %). Redo anorectoplasty was not associated with prolapse. Symptoms were present in 11 patients (28 %): in 7 % with minimal, 33 % with moderate and 77 % with evident prolapse. Nine patients (2 moderate, 7 evident) underwent surgical correction. CONCLUSION: Severe ARMs, tethered cord, vertebral anomalies, colostomy, and LAARP predispose to rectal prolapse. Classifying prolapse allows to predict symptoms and need for surgical correction, and to compare outcomes among different centers.

Peritoneal tuberculosis due to multidrug-resistant Mycobacterium tuberculosis.

The emergence of drug-resistant Mycobacterium tuberculosis has been widely reported throughout the world, but there are very few data regarding children. We describe the case of a 14-year-old Peruvian adolescent who had been living in Italy since the age of 8 years and was diagnosed as having peritoneal tuberculosis (TB). While she was receiving first-line anti-TB therapy, she developed pyrazinamide-associated thrombocytopenia and cultures revealed a multidrug-resistant strain of Mycobacterium tuberculosis. Pyrazinamide, rifampicin and isoniazid were replaced by moxifloxacin, which was continued for 9 months together with ethambutol. The patient recovered without experiencing any drug-related adverse event or the recurrence of TB in the following year. In conclusion, this case illustrates some of the problems that can arise when multidrug-resistant TB has to be treated in children and adolescents, and also highlights the fact that further studies are needed to clarify which drugs should be used and for how long.

Anorectal Malformations: Ideal Surgery Timing to Reduce Incontinence and Optimize QoL.

Anorectal malformations (ARMs) are rare and involve a wide spectrum of malformations. Prenatal diagnosis is often incomplete, and the diagnostic pathway is started during the newborn period to identify the type of malformation and the correct treatment. This retrospective study included patients between 8 and 18 y.o. diagnosed with ARM, referring to Our Clinic. We proposed two questionnaires, Rintala Bowel Function Score and the Fecal Incontinence Quality of Life Scale, and we defined four groups referring to surgical timing (age in months < 3, 3-6, 6-9, >9). In total, 74 patients were recruited (mean age 13.05 ± 2.80 y.o.), and data analysis showed a significant relationship between comorbidity and surgical timing. Moreover, timing was related to outcome in terms of fecal continence (better if surgery performed before 3 months) and Quality of Life (QoL). QoL, however, is influenced by other factors (emotional and social life, psychological sphere and take of care of chronic disease). We considered rehabilitation programs, more often practiced by children who underwent surgery after 9 months, to maintain an appropriate relational life. This study highlights the importance of surgical timing as the first step of a multidisciplinary follow-up, taking care of the child in every phase of his growth, tailored to the single patient.

Tethered Cord and Anorectal Malformations: A Case Series.

INTRODUCTION: The clinical manifestation of a stretched low-lying cone (LLC) is represented by the tethered cord syndrome (TCS) with cutaneous, urologic, neurologic, and orthopaedic dysfunctions. TC is frequently found in patients with anorectal malformations (ARMs). The aim of our article is to report a series of patients affected by LLC and ARMs and evaluate their management and long-term follow-up results. MATERIALS AND METHODS: We performed a retrospective analysis over a period of 15 years including patients with ARM and TC and excluding those with severe polymalformations. We collected information related to the types of malformations and demographic data. We analyzed their management (perinatal protocol, radiological investigations, surgery, and multidisciplinary follow-up). QOL was assessed through the International Classification of Functioning, Disability, and Health for Children and Youth (ICF-CY). RESULTS: Thirty-three patients among 210 ARM cases had TC (16%). Eleven of them underwent neurosurgery. One patient had retethering; out of 11 patients, 4 remained stable and 6 improved after surgery (UDS normalization and resolution of symptoms). At a mean follow-up of 10 years, four patients were on clean intermittent catheterization and five on the Peristeen transanal irrigation. The majority of patients were defined as 3 (from 1-bad to 5-excellent) for their physical and mental state. CONCLUSION: The use of MRI is considered to complete the ARM screening in detecting TC. The multidisciplinary approach is crucial and helps in defining the management of patients. In fact, it is not clear how the features of ARM and TC affect each other. The selection of cases for surgery should take into account the critical elements.

Endoscopic Surveillance for Congenital Diaphragmatic Hernia: Unexpected Prevalence of Silent Esophagitis.

Introduction Gastroesophageal reflux disease (GERD) is a frequent comorbidity after congenital diaphragmatic hernia (CDH) repair. Our aim was to evaluate the clinical and endoscopic prevalence of esophagitis in a long-term follow-up of CDH patients. Materials and Methods Patients operated on for posterolateral CDH and undergoing general anesthesia for concomitant pathologies between January and October 2013 were included in the study. GERD was investigated both clinically (Manterola questionnaire) and endoscopically. The severity of esophagitis was evaluated according to the Hetzel-Dent classification and multiple biopsies were performed. The correlation between clinical score and severity of esophagitis was evaluated. Results Twelve patients were included in the study (mean age: 14.5 years; range, 9-18 years). Only three children (25%) had a pathological questionnaire. At endoscopy, three children (25%) were affected by grade 1 esophagitis, six (50%) by grade 2, two (17%) by grade 3, and one (8%) by grade 4. One of the children presented Barrett esophagus. A moderate negative correlation was found between clinical data and endoscopic findings (r: -0.54 and p: 0.067). Conclusion Even in the absence of symptoms, esophagitis revealed to have a high prevalence in CDH patients. A long-term clinical and instrumental follow-up is mandatory to early diagnose and treat GERD.

Esophageal atresia with proximal tracheoesophageal fistula: a missed diagnosis.

AIM OF THE STUDY: This retrospective study was performed to compare the relative incidence of esophageal atresia (EA) with proximal tracheoesophageal fistula (PTEF) at our institution with those reported in literature and to test the hypothesis that our higher relative incidence is caused by the routine use of tracheoscopy. METHODS: A total of 204 children with EA were managed at our institution from 1981 to 2012. The type of EA and the diagnostic assessment were noted, and the relative incidence of PTEF was calculated. For patients managed from 1981 to 2003 (Group 1), the PTEF was diagnosed by contrast esophagogram or during surgical repair. For those born after 2004 (Group 2), the final diagnosis was made by routine rigid tracheoscopy performed preoperatively. The relative incidence of PTEF was compared between these two groups and with those reported in 15 selected published large series, encompassing 4197 patients with EA. MAIN RESULTS: Of 204 patients with EA, 10 had PTEF, with a relative incidence of 4.9%, statistically higher than those reported in reference group (1.14%, P<0.001). The routine employ of tracheoscopy involved a higher relative incidence of PTEF (Group 2=11.11%, Group 1=3.14%, P=0.038). The age of diagnosis of PTEF was 2.8 days for children of Group 2 and 4.2 days for Group 1 (P=0.038). CONCLUSION: The presence of the proximal TEF should be always ruled out before surgery. Routine employ of rigid tracheoscopy avoids delay of the diagnosis, improves diagnostic accuracy, and involves a higher relative incidence of proximal fistul. This procedure should be recommended in children undergoing EA repair.

The role of laparoscopy in newborns affected by NEC.

INTRODUCTION: For many years, laparoscopic procedures have been reported in the literature in pediatrics also. In this article, we report their experiences of the use of gasless laparoscopy in 8 newborns affected by necrotizing enterocolitis (NEC). MATERIALS AND METHODS: From January 2007 to May 2008, 8 patients affected by stage 1-2 NEC were treated at the Department of Pediatric Surgery, Fondazione Policlinico Milan (Milan, Italy). Of those, 3 patients presented with a birth weight below 1.5 kg. RESULTS: All patients were submitted at gasless laparoscopy. In 6 of 8 patients, a covered perforation was detected; in 5 cases, the perforation was on the posterior wall of the ascending colon, and in 1, a perforation of the transverse colon was detected. In these 6 of 8 patients, the procedure was converted to formal laparotomy, with colonic resection and primary anastomosis. In 2 of 8 patients, a diffuse necrotizing enteritis of the small bowel was reported, without evidence of perforation; two drains were placed and continued abdominal washout with antibiotics solution was maintained for 48 hours, associated with systemic therapy. All patients were maintained on systemic antibiotic therapy for 7 days with regression of sepsis; all patients survived and were discharged in good general condition. At follow-up of 3 months, none of the patients presented with complications. DISCUSSION: We believe that the decision to perform a laparoscopy, despite the very low weight of the patient, was crucial in the management of nondetected perforation at X-ray. Retrospectively, laparoscopy would be the best option to define the presence of NEC without a perforation, which may only require washout of the cavity that can be also managed with this technique. CONCLUSIONS: We believe that laparoscopy can be easily managed also in newborns and small for gestational age neonates, reducing the morbidity of laparotomy for suspicion of perforation in patients affected by NEC who do not respond to medical treatment.