Case report: Neonatal-onset inflammatory bowel disease due to novel compound heterozygous mutations in DUOX2

Very Early Onset Inflammatory Bowel Disease (VEO-IBD) is potentially associated with genetic disorders of the intestinal epithelial barrier or inborn errors of immunity (IEI). Dual oxidase 2 (DUOX2), an H2O2-producing NADPH oxidase expressed at apical enterocyte membranes, plays a crucial role in innate defense response. Biallelic DUOX2 mutations have been described only in two patients with VEO-IBD to date. We report the case of a 1-month-old female infant who presented persistent high C-reactive protein (CRP) levels from birth and anemia. Positive occult blood and very high calprotectin in the stool were detected and abdominal ultrasound showed thickened last ileal loop. Full endoscopy evaluation revealed important colon stenosis with multiple pseudo-polyploidy formations that resulted refractory to steroid therapy, requiring a partial colic resection. Histological examination of biopsy samples showed morphological features of IBD. Whole Exome Sequencing (WES) disclosed compound heterozygous variants in the DUOX2 gene: the pathogenic c.2524C>T; p.Arg842Ter and the variant of uncertain significance (VUS) c.3175C>T; p.Arg1059Cys. Molecular and functional studies showed the presence of mutant DUOX2 in the intestinal epithelium of the patient, albeit with at least 50% decreased catalytic activity. In conclusion, we describe the third patient to date with compound heterozygous variants of DUOX2, responsible for monogenic neonatal-IBD. This case expands the knowledge about Mendelian causes of VEO-IBD and DUOX2 deficiency. We suggest that DUOX2 should be part of the diagnostic evaluation of patients with suspected monogenic VEO-IBD

Diagnostic Tests in Pediatric Constipation

Constipation is one of the most common gastrointestinal symptoms in children. With a median reported prevalence of 12%, it accounts for about 25% of all pediatric gastroenterology consultations. The majority of children suffers functional constipation and do not usually require any diagnostic testing. For those children not responding to conventional medical treatment or in the presence of a more significant clinical picture, however, an accurate instrumental assessment is usually recommended to evaluate either the underlying pathophysiologic mechanisms or a possible organic etiology. The present review analyzes the possible diagnostic investigations for severely constipated children, focusing on their actual indications and their utility in clinical practice. Over the last decade, there has been a remarkable increase in our knowledge of normal and abnormal colonic and anorectal motility in children, and a number of different techniques to measure transit and motility have been developed and are discussed in this narrative review

Targeting Epidermal Growth Factor Receptor (EGFR) in Pediatric Colorectal Cancer

Background: Colorectal carcinoma (CRC) is very rare in the pediatric and adolescent age range and clinical management is performed according to adult protocols. We report, for the first time in the literature, a case of a child with metastatic CRC successfully treated with panitumumab associated to chemotherapy. Methods: A twelve-year-old male was diagnosed with CRC with nodal metastasis and peritoneal neoplastic effusion. After performing a genetic evaluation, in light of the absence of mutations in RAS family genes, anti-Epidermal Growth Factor Receptor (EGFR) monoclonal antibody, panitumumab, was added to chemotherapy FOLFOXIRI. Results: The child successfully responded to therapy with normalization of the Carbohydrate Antigen (CA) 19.9 value after the third cycle of treatment. After the sixth cycle, he underwent surgery that consisted in sigmoid resection with complete D3 lymphadenectomy. At histological evaluation, no residual neoplastic cells were detectable in the surgical specimen. He completed 12 cycles of chemotherapy plus panitumomab and he is alive without disease 14 months from diagnosis. Conclusions: Our results suggest performing mutational screening for colorectal cancer also in the pediatric setting, in order to orient treatment that should include targeted therapies

Association between body positioning and gastroesophageal reflux in paediatric age

Postural measures are frequently recommended for gastroesophageal reflux (GER) symptoms, despite limited evidence. This was the first study to assess the impact of upright and recumbent body positions on GER episodes in children and adolescents, not just infants

An uncommon cause of abdominal pain in a child: Meckel diverticulum

Meckel diverticulum, a common congenital anomaly of the small intestine, can be responsible of several complications due to the presence of ectopic gastric mucosa and represents a challenge for diagnosis. We present the case of a 11-year boy suffering from intestinal pain and bleeding in which radiological examinations unexpectedly raised the suspicion of Meckel diverticulum. The diagnosis was confirmed using 99mTc-pertechnetate scintigraphy. At surgery, a fistulous tract between Meckel diverticulum and an inflamed appendix was found. The authors discuss the role of medical nuclear imaging which, notwithstanding its limitations, is of fundamental importance to achieve a correct and timely diagnosis. This is of particular relevance in unusual cases, as the one presented, in which Meckel diverticulum is found concurrently with other intestinal abnormalities

Anastomotic Strictures after Esophageal Atresia Repair: Incidence, Investigations, and Management, Including Treatment of Refractory and Recurrent Strictures

Improved surgical techniques, as well as preoperative and postoperative care, have dramatically changed survival of children with esophageal atresia (EA) over the last decades. Nowadays, we are increasingly seeing EA patients experiencing significant short- and long-term gastrointestinal morbidities. Anastomotic stricture (AS) is the most common complication following operative repair. An esophageal stricture is defined as an intrinsic luminal narrowing in a clinically symptomatic patient, but no symptoms are sensitive or specific enough to diagnose an AS. This review aims to provide a comprehensive view of AS in EA children. Given the lack of evidence-based data, we critically analyzed significant studies on children and adults, including comments on benign strictures with other etiologies. Despite there is no consensus about the goal of the luminal diameter based on the patient’s age, esophageal contrast study, and/or endoscopy are recommended to assess the degree of the narrowing. A high variability in incidence of ASs is reported in literature, depending on different definitions of AS and on a great number of pre-, intra-, and postoperative risk factor influencing the anastomosis outcome. The presence of a long gap between the two esophageal ends, with consequent anastomotic tension, is determinant for stricture formation and its response to treatment. The cornerstone of treatment is endoscopic dilation, whose primary aims are to achieve symptom relief, allow age-appropriate capacity for oral feeding, and reduce the risk of pulmonary aspiration. No clear advantage of either balloon or bougie dilator has been demonstrated; therefore, the choice is based on operator experience and comfort with the equipment. Retrospective evidences suggest that selective dilatations (performed only in symptomatic patients) results in significantly less number of dilatation sessions than routine dilations (performed to prevent symptoms) with equal long-term outcomes. The response to dilation treatment is variable, and some patients may experience recurrent and refractory ASs. Adjunctive treatments have been used, including local injection of steroids, topical application of mitomycin C, and esophageal stenting, but long-term studies are needed to prove their efficacy and safety. Stricture resection or esophageal replacement with an interposition graft remains options for AS refractory to conservative treatments

La pH-impedenzometria esofagea in età pediatrica: position paper SIGENP

Esophageal pH impedance is the most accurate diagnostic procedure for gastro esophageal reflux diagnosis. In the last ten years, due to many clinical studies, its use in the world has been gradually, implemented especially in newborns and in children. However, still some factors like the small size of the reference values in children and poor therapeutic options limit its current clinical impact. Through a revision of recent scientific evidences,this document was produced by the Neurogastroenterology and disease-acid-related working group of the Italian Society of Gastroenterology, Hepatology and Pediatric Nutrition (SIGENP) in order to standardize clinical indications, methodology, data analysis and pH reporting – esophageal impedance measurement in children and provide a practical reference for the diagnostic approach to children with symptoms of gastro-esophageal reflux

Decellularized esophageal tubular scaffold microperforated by quantum molecular resonance technology and seeded with mesenchymal stromal cells for tissue engineering esophageal regeneration

Current surgical options for patients requiring esophageal replacement suffer from several limitations and do not assure a satisfactory quality of life. Tissue engineering techniques for the creation of customized “self-developing” esophageal substitutes, which are obtained by seeding autologous cells on artificial or natural scaffolds, allow simplifying surgical procedures and achieving good clinical outcomes. In this context, an appealing approach is based on the exploitation of decellularized tissues as biological matrices to be colonized by the appropriate cell types to regenerate the desired organs. With specific regard to the esophagus, the presence of a thick connective texture in the decellularized scaffold hampers an adequate penetration and spatial distribution of cells. In the present work, the Quantum Molecular Resonance® (QMR) technology was used to create a regular microchannel structure inside the connective tissue of full-thickness decellularized tubular porcine esophagi to facilitate a diffuse and uniform spreading of seeded mesenchymal stromal cells within the scaffold. Esophageal samples were thoroughly characterized before and after decellularization and microperforation in terms of residual DNA content, matrix composition, structure and biomechanical features. The scaffold was seeded with mesenchymal stromal cells under dynamic conditions, to assess the ability to be repopulated before its implantation in a large animal model. At the end of the procedure, they resemble the original esophagus, preserving the characteristic multilayer composition and maintaining biomechanical properties adequate for surgery. After the sacrifice we had histological and immunohistochemical evidence of the full-thickness regeneration of the esophageal wall, resembling the native organ. These results suggest the QMR microperforated decellularized esophageal scaffold as a promising device for esophagus regeneration in patients needing esophageal substitution

Image2_Decellularized esophageal tubular scaffold microperforated by quantum molecular resonance technology and seeded with mesenchymal stromal cells for tissue engineering esophageal regeneration.jpg

Current surgical options for patients requiring esophageal replacement suffer from several limitations and do not assure a satisfactory quality of life. Tissue engineering techniques for the creation of customized “self-developing” esophageal substitutes, which are obtained by seeding autologous cells on artificial or natural scaffolds, allow simplifying surgical procedures and achieving good clinical outcomes. In this context, an appealing approach is based on the exploitation of decellularized tissues as biological matrices to be colonized by the appropriate cell types to regenerate the desired organs. With specific regard to the esophagus, the presence of a thick connective texture in the decellularized scaffold hampers an adequate penetration and spatial distribution of cells. In the present work, the Quantum Molecular Resonance® (QMR) technology was used to create a regular microchannel structure inside the connective tissue of full-thickness decellularized tubular porcine esophagi to facilitate a diffuse and uniform spreading of seeded mesenchymal stromal cells within the scaffold. Esophageal samples were thoroughly characterized before and after decellularization and microperforation in terms of residual DNA content, matrix composition, structure and biomechanical features. The scaffold was seeded with mesenchymal stromal cells under dynamic conditions, to assess the ability to be repopulated before its implantation in a large animal model. At the end of the procedure, they resemble the original esophagus, preserving the characteristic multilayer composition and maintaining biomechanical properties adequate for surgery. After the sacrifice we had histological and immunohistochemical evidence of the full-thickness regeneration of the esophageal wall, resembling the native organ. These results suggest the QMR microperforated decellularized esophageal scaffold as a promising device for esophagus regeneration in patients needing esophageal substitution.</p