Replogle Modified Endoscopic Vacuum-Assisted Closure (EVAC) Therapy: A New Strategy to Treat Anastomotic Leakage and Esophageal Perforation.

BACKGROUND: Anastomotic leakage (AL) and esophageal perforation are life-threatening complications following surgery or endoscopic dilations. "Replogle modified EVAC therapy" consists of placing a Replogle tube directly into the lumen or within an abscess cavity and remove by suction all intra-cavity fluids and secretion with a continuous low-pressure suction, promoting granulation tissue proliferation, thereby gradually decreasing the cavity size. The aim of our study was to evaluate the technical feasibility, safety, and efficacy of this technique in pediatric patients. METHODS: A retrospective review charts of consecutive pediatric patients that were treated with "Replogle modified EVAC therapy" at our pediatric referral center between 2013 and 2022 was conducted. The clinical, endoscopic, radiological, and surgical information and data of patients were collected and revised as well as their follow-up and outcomes. RESULTS: Ten patients (6/10 male; mean age: 7.8 y.o., range: 1.1-18 y.o.) were treated using the "Replogle modified EVAC therapy". Four out of ten patients developed esophageal perforations after endoscopic procedures. Six out of the ten enrolled patients had AL complications after surgical operations. All patients were successfully treated. There were no technical failures or complications with device placement. Mean treatment duration was 16 days (range 7-41 days). No additional treatment was needed for complete leak resolution. CONCLUSIONS: "Replogle modified EVAC therapy" represents a promising and mini-invasive method to treat esophageal perforations and post-surgical leak in the paediatric age group. In our experience, the use of this technique was safe, effective, and particularly well suited also in complex paediatric patients. LEVEL OF EVIDENCE: IV.

De Novo Crohn's Disease in Children With Ulcerative Colitis Undergoing Ileal Pouch-Anal Anastomosis: A Multicenter, Retrospective Study From the Pediatric IBD Porto Group of the ESPGHAN.

BACKGROUND AND AIMS: We sought to define the prevalence and to characterize possible predictive factors of Crohn's disease (CD) occurring in children with ulcerative colitis (UC) after ileal pouch-anal anastomosis (IPAA). METHODS: This was a multicenter, retrospective study including 15 centers of the Porto IBD group of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition. Children with a confirmed diagnosis of UC undergoing colectomy with IPAA and a minimal follow up of 6 months were identified. The following data were collected: demographic data; endoscopic and histologic data; disease activity; laboratory exams; therapeutic history; indication for surgery, type, and timing; and IPAA functional outcomes and complications. In de novo CD cases, time of diagnosis, phenotype, location, and therapies were gathered. RESULTS: We identified 111 UC children undergoing IPAA from January 2008 to June 2018 (median age at colectomy: 13 years; age range: 1-18 years; female/male: 59/52). The median time from diagnosis to colectomy was 16 (range, 0-202) months. At the last follow-up, 40 (36%) of 111 children developed pouchitis. The criteria for de novo CD were met in 19(17.1%) of 111 children with a 25-month median (range, 3-61 months). At last follow-up, 12 (63.1%) of 19 were treated with biologics and in 5 (26.3%) of 19 children, the pouch was replaced with definitive ileostomy. In a multivariable logistic regression model, decreased preoperative body mass index z scores (odds ratio, 2.2; 95% confidence interval, 1.1-4.4; P = .01) resulted as the only variable associated with CD development. CONCLUSIONS: Children with UC undergoing IPAA carry a high risk of developing subsequent CD. De novo CD cases showed decreased preoperative body mass index z scores, identifying a poor nutritional status as a possible predictive factor.

This is the largest European study describing the prevalence of Crohn's disease (CD) development in children with ulcerative colitis undergoing subtotal colectomy with ileal pouch­anal anastomosis. Children affected by ulcerative colitis carry a higher risk when compared with adults to develop de novo CD after surgery. On the other hand, the multivariate analysis identified decreased values of preoperative body mass index z scores as a possible predictor of new-onset CD.

Evaluation of Safety and Immunogenicity of BNT162B2 mRNA COVID-19 Vaccine in IBD Pediatric Population with Distinct Immune Suppressive Regimens.

Patients affected by Inflammatory Bowel Disease (IBD) present higher risk for infection and suboptimal response upon vaccination. The immunogenicity of SARS-CoV2 vaccination is still largely unknown in adolescents or young adults affected by IBD (pIBD). We investigated the safety and immunogenicity of the BNT162B2 mRNA COVID-19 vaccine in 27 pIBD, as compared to 30 healthy controls (HC). Immunogenicity was measured by anti-SARS-CoV2 IgG (anti-S and anti-trim Ab) before vaccination, after 21 days (T21) and 7 days after the second dose (T28). The safety profile was investigated by close monitoring and self-reported adverse events. Vaccination was well tolerated, and short-term adverse events reported were only mild to moderate. Three out of twenty-seven patients showed IBD flare after vaccination, but no causal relationship could be established. Overall, pIBD showed a good humoral response upon vaccination compared to HC; however, pIBD on anti-TNFα treatment showed lower anti-S Ab titers compared to patients receiving other immune-suppressive regimens (p = 0.0413 at first dose and p = 0.0301 at second dose). These data show that pIBD present a good safety and immunogenicity profile following SARS-CoV-2 mRNA vaccination. Additional studies on the impact of specific immune-suppressive regimens, such as anti TNFα, on immunogenicity should be further investigated on larger cohorts.

Real-Life Use of Biosimilars in Pediatric Inflammatory Bowel Disease: A Nation-Wide Web Survey on Behalf of the SIGENP IBD Working Group.

OBJECTIVE: The aim was to assess the awareness and real-life use of biosimilars in inflammatory bowel disease (IBD) among the members of the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP). METHODS: An anonymous web survey involving all SIGENP IBD units which can prescribe biosimilars was conducted between July 1st and December 1st, 2020. The questionnaire included 18 questions addressing the most relevant aspects of biosimilars in pediatric IBD, i.e., advantages, disadvantages, costs, traceability, general knowledge, and real-life use. A descriptive analysis of responses was performed. RESULTS: Responses came from 26 pediatric IBD units in Italy, with representation of the North, the Center, and the South of Italy. The majority of participants (n = 20) had spent > 10 years caring for pediatric IBD patients, and worked in a center which had between 100 and 500 registered pediatric IBD patients (n = 14). Most participants (n = 18) reported they were aware that biosimilars have similar efficacy and safety to those of the originator, and all regarded cost-sparing as the main advantage of biosimilars. Most respondents (n = 20) reported they switch from originator to biosimilar in their everyday clinical practice, mostly during the maintenance phase. Most respondents (n = 20) registered no acute adverse events. Nearly all participants felt totally or very confident in using biosimilars. CONCLUSIONS: A few years after the introduction of the first biosimilar into the market, real-life data coming from the major IBD units in Italy confirm a favorable and confident position on the use of biosimilars in pediatric IBD.

Gastric cancer, inflammatory bowel disease and polyautoimmunity in a 17-year-old boy: CTLA-4 deficiency successfully treated with Abatacept.

Gut involvement is frequent in immunologic disorders, especially with inflammatory manifestations but also with cancer. In the last years, advances in functional and genetic testing have improved the diagnostic and therapeutic approach to immune dysregulation syndromes. CTLA-4 deficiency is a rare disease with variable phenotype, ranging from absence of symptoms to severe multisystem manifestations and complications. We describe a rare case of CTLA-4 deficiency in a boy with gastric cancer, very early onset inflammatory bowel disease and polyautoimmunity, the second-ever reported in the literature with the same characteristics. A 17-year-old boy was referred to Bambino Gesù Children's Hospital of Rome, a tertiary care center, for a gastric mass and a long-term history of very early onset inflammatory bowel disease, diabetes mellitus type 1, polyarthritis and psoriasis. Histology of gastric biopsies revealed the presence of neoplastic signet ring cells. Imaging staging showed localized cancer; therefore, the patient underwent subtotal gastrectomy with termino-lateral gastro-jejunal anastomosis. Immunological work up and genetic testing by next-generation sequencing panels for primary immunodeficiencies led to the diagnosis of CTLA-4 deficiency. Good disease control was obtained with the administration of Abatacept. The patient experienced an asymptomatic SARS-CoV-2 infection without any concern. Eighteen months after treatment initiation, the patient is alive and well. Immunologic and genetic testing, such as next-generation sequencing, should always be part of the diagnostic approach to patients with complex immune dysregulation syndrome, severe clinical course, poor response to treatments or cancer. The early recognition of the monogenic disease is the key for disease management and targeted therapy.

Scoring Endoscopy in Pediatric Inflammatory Bowel Disease: A Way to Improve Quality.

OBJECTIVES AND STUDY: There is a large interobserver variability in evaluating mucosal lesions of inflammatory bowel disease (IBD), especially in pediatric patients. This multicenter prospective observational study aims to evaluate interobserver agreement (IOA) among pediatric endoscopists in assigning validated IBD endoscopic scores in children. METHODS: Fifteen videos of follow-up ileocolonoscopies in children with IBD were recorded and selected as cases. Eleven pediatric endoscopists from different centers blindly evaluated all videos and calculated scores: either Ulcerative Colitis Endoscopic Index of Severity (UCEIS) or Simple Endoscopic Score for Crohn Disease (SES-CD). Scores from all reviewers were compared in order to calculate IOA for general videos and specific sections. Scores from an expert adult reader were used to calculate possible reviewer's characteristics affecting scores' reliability. RESULTS: Intraclass correlation was 0.298 (95% confidence interval [CI]: 0.13-0.55) for ulcerative colitis (UC) and 0.266 (0.11-0.52) for Crohn disease (CD). When a disease activity categorization was adopted (remission, mild, moderate, severe activity) Fleiss kappa coefficient was 0.408 (0.29-0.53) for UC and 0.552 (0.43-0.73) for CD. When stratified by item, vascular pattern of UC was the most reliable item IC: 0.624 (0.321-0.854). In multivariable analysis, none of the reviewer's characteristics affected the readers' errors. CONCLUSIONS: This multicenter study shows low agreement among pediatric endoscopists in evaluating endoscopic scores in children with IBD. By using disease activity categorization, agreement slightly increased, mostly for CD. All readers showed a low-grade concordance with the expert adult gastroenterologist's evaluations. Future-specific training programs should be considered to increase IOA in using IBD endoscopic activity scores.

Impact of COVID-19 pandemic on the management of paediatric inflammatory bowel disease: An Italian multicentre study on behalf of the SIGENP IBD Group.

BACKGROUND: IBD management has been significantly affected during the COVID-19 lockdown with potential clinical issues. AIMS: The aim of this study was to analyse the impact of COVID-19 pandemic on the Italian paediatric IBD cohort. METHODS: This was a multicentre, retrospective, cohort investigation including 21 different Italian IBD referral centres. An electronic data collection was performed among the participating centres including: clinical characteristics of IBD patients, number of COVID-19 cases and clinical outcomes, disease management during the lockdown and the previous 9 weeks. RESULTS: 2291 children affected by IBD were enrolled. We experienced a significant reduction of the hospital admissions [604/2291 (26.3%) vs 1281/2291 (55.9%); p < 0.001]. More specifically, we observed a reduction of hospitalizations for new diagnosis (from n = 44 to n = 27) and endoscopic re-evaluations (from n = 46 to n = 8). Hospitalization for relapses and surgical procedures remained substantially unchanged. Biologic infusions did not significantly vary [393/2291 (17.1%) vs 368/2291 (16%); p = 0.3]. Telemedicine services for children with IBD were activated in 52.3% of the centres. In 42/2291(1.8%) children immunosuppressive therapies were adapted due to the concurrent COVID-19 pandemic. CONCLUSION: Due to the several limitations of the lockdown, cares for children with IBD have been kept to minimal standards, giving priorities to the urgencies and to biologics' infusions and implementing telemedicine services.

Esophageal Retained Lithium Battery in Children Younger than 6 Years: A Prompt Structured Multidisciplinary Approach Is Essential to Reduce Long-Term Consequences.

OBJECTIVES: Disk battery esophageal retention in children younger than 6 years represents an increasing endoscopic emergency, followed by a relevant risk of life-threatening late complications. Surgical removal after a failed endoscopic approach is rarely reported in the literature. We describe our experience in this scenario. METHODS: Two female asymptomatic patients aged 26 and 29 months presented within 4 hours after a witnessed ingestion of a 2-cm, 3-V lithium battery (CR2032) retained in the cervical esophagus. Both patients underwent a prolonged unsuccessful emergent endoscopic removal with a flexible instrument performed by an adult gastroenterologist. Both batteries fused with the esophageal wall were extracted through a longitudinal left cervical esophagotomy combined with minimal resection of necrotic tissues and repaired over a 12F feeding tube. RESULTS: Patients were extubated after 12 and 72 hours, respectively. Contrast study was performed after 20 and 13 days, respectively, before resuming oral feeding. At endoscopy, the first patient developed a 3-cm-long severe esophageal stenosis (35th day), followed by an asymptomatic tracheoesophageal fistula (60th day), which was conservatively treated. After spontaneous resolution of the tracheoesophageal fistula, esophageal stenosis progressed, partially responsive to esophageal stenting. Short esophagectomy is under evaluation. The second patient developed an asymptomatic limited stenosis, not requiring dilatation. CONCLUSIONS: The emergent management of lithium battery ingestion needs a structured timely multidisciplinary approach in the emergency department, an experienced pediatric endoscopist, and a simultaneous engagement of pediatric surgical expertise, even in patients who do not show bleeding, to reduce esophageal exposure time to high-voltage current released by batteries, which represents the main factor conditioning tissue damage and prognosis.

Evaluation of Gastroesophageal Reflux Disease 1 Year after Esophageal Atresia Repair: Paradigms Lost from a Single Snapshot?

OBJECTIVE: To analyze the findings of both multichannel intraluminal impedance with pH (MII-pH) and endoscopy/histopathology in children with esophageal atresia at age 1 year, according to current recommendations for the evaluation of gastroesophageal reflux disease (GERD) in esophageal atresia. STUDY DESIGN: We retrospectively reviewed both MII-pH and endoscopy/histopathology performed in 1-year-old children with esophageal atresia who were followed up in accordance with international recommendations. Demographic data and clinical characteristics were also reviewed to investigate factors associated with abnormal GERD investigations. RESULTS: In our study cohort of 48 children with esophageal atresia, microscopic esophagitis was found in 33 (69%) and pathological esophageal acid exposure on MII-pH was detected in 12 (25%). Among baseline variables, only the presence of long-gap esophageal atresia was associated with abnormal MII-pH. Distal baseline impedance was significantly lower in patients with microscopic esophagitis, and it showed a very good diagnostic performance in predicting histological changes. CONCLUSIONS: Histological esophagitis is highly prevalent at 1 year after esophageal atresia repair, but our results do not support a definitive causative role of acid-induced GERD. Instead, they support the hypothesis that chronic stasis in the dysmotile esophagus might lead to histological changes. MII-pH may be a helpful tool in selecting patients who need closer endoscopic surveillance and/or benefit from acid suppression.

Management of paediatric IBD after the peak of COVID-19 pandemic in Italy: A position paper on behalf of the SIGENP IBD working group.

Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2, spreading in Italy during the first months of 2020, abruptly changed the way of practicing medicine in this country. As a consequence of the lockdown, the diagnostic and therapeutic management of paediatric chronic conditions, such as inflammatory bowel disease (IBD) has been affected. During the peak of COVID-19 pandemic, elective visits, endoscopies and infusions have been postponed, with potential clinical and psychological impact on disease course and a high likelihood of increasing waiting lists. While slowly moving back towards normality, clinicians need to recognize the best ways to care for patients with IBD, carefully avoiding risk factors for new potential epidemic outbreaks. In this uncertain scenario until the development and spread of COVID-19 vaccine, it is necessary to continue to operate with caution. Hereby we provide useful indications for a safer and gradual restarting of routine clinical activities after COVID-19 peak in Italy.

Fecal Microbiota Transplant in Two Ulcerative Colitis Pediatric Cases: Gut Microbiota and Clinical Course Correlations.

Fecal microbiota transplantation (FMT) is a promising strategy in the management of inflammatory bowel disease (IBD). The clinical effects of this practice are still largely unknown and unpredictable. In this study, two children affected by mild and moderate ulcerative colitis (UC), were pre- and post-FMT monitored for clinical conditions and gut bacterial ecology. Microbiota profiling relied on receipts' time-point profiles, donors and control cohorts' baseline descriptions. After FMT, the improvement of clinical conditions was recorded for both patients. After 12 months, the mild UC patient was in clinical remission, while the moderate UC patient, after 12 weeks, had a clinical worsening. Ecological analyses highlighted an increase in microbiota richness and phylogenetic distance after FMT. This increase was mainly due to Collinsella aerofaciens and Eubacterium biforme, inherited by respective donors. Moreover, a decrease of Proteus and Blautia producta, and the increment of Parabacteroides, Mogibacteriaceae, Bacteroides eggerthi, Bacteroides plebeius, Ruminococcus bromii, and BBacteroidesovatus were associated with remission of the patient's condition. FMT results in a long-term response in mild UC, while in the moderate form there is probably need for multiple FMT administrations. FMT leads to a decrease in potential pathogens and an increase in microorganisms correlated to remission status.

Increased levels of 5',8-Cyclopurine DNA lesions in inflammatory bowel diseases.

Chronic inflammation is estimated to be a causative factor in a variety of diseases. Under inflammatory conditions reactive oxygen species (ROS) and nitrogen species (RNS) are released leading to DNA damage accumulation and genomic instability. Purine 5',8-cyclo-2'-deoxynucleosides (cPu) are oxidative DNA lesions, exclusively derived from the attack of HO• radicals, which are known to have cytotoxic and mutagenic properties. Herein, we have analyzed the presence of cPu in genomic DNA isolated from fresh colon and visceral adipose tissue biopsies collected from inflammatory bowel diseases (IBD)-affected patients and severely obese subjects, respectively, versus what observed in the control specimens. In colon biopsies, characterized by a higher gene expression level of inducible nitric oxide synthase (iNOS), a significant increase of 8-oxo-7,8-dihydro-2'-deoxyadenosine (8-oxo-dA) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) lesions and an accumulation of both diastereomeric cPu have been detected. In contrast, the 8-oxo-dA and 8-oxo-dG levels were extremely lower compared to the colon tissues values and no accumulation of cPu, in the inflamed visceral adipose tissue biopsies isolated from bariatric patients versus the lean counterpart was reported. In addition, in adipose tissue undetectable levels of iNOS have been found. These data suggest a potential involvement of cPu in the colon cancer susceptibility observed in IBD patients.

Diagnostic Approach to Monogenic Inflammatory Bowel Disease in Clinical Practice: A Ten-Year Multicentric Experience.

BACKGROUND AND AIMS: Multiple monogenic disorders present as very early onset inflammatory bowel disease (VEO-IBD) or as IBD with severe and atypical features. Establishing a genetic diagnosis may change patients' management and prognosis. In this study, we describe the diagnostic approach to suspected monogenic IBD in a real clinical setting, discussing genetic and phenotypic findings and therapeutic implications of molecular diagnosis. METHODS: Information of patients with VEO-IBD and early onset IBD with severe/atypical phenotypes (EO-IBD s/a) managed between 2008-2017 who underwent a genetic workup were collected. RESULTS: Ninety-three patients were included, and 12 (13%) reached a genetic diagnosis. Candidate sequencing (CS) was performed in 47 patients (50%), and next generation sequencing (NGS) was performed in 84 patients (90%). Candidate sequencing had a good diagnostic performance only when guided by clinical features specific for known monogenic diseases, whereas NGS helped finding new causative genetic variants and would have anticipated one monogenic diagnosis (XIAP) and consequent bone marrow transplant (BMT). Patients with monogenic IBD more frequently were male (92% vs 54%; P = 0.02), had extraintestinal findings (100% vs 34%; P < 0.001), and had disease onset ≤1 month of life (25% vs 1%; P = 0.006). Genetic diagnosis impacted patient management in 11 patients (92%), 7 of whom underwent BMT. CONCLUSION: A genetic diagnosis can be established in a significant proportion of suspected monogenic IBD and has an impact on patients' management. Candidate sequencing may be deployed when clinical findings orientate toward a specific diagnosis. Next generation sequencing should be preferred in patients with nonspecific phenotypes.

Pouchitis in pediatric ulcerative colitis: A multicenter study on behalf of Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition.

BACKGROUND: Data on the epidemiology and risk factors for pouchitis following restorative proctocolectomy and ileal pouch-anal anastomosis (IPAA) in pediatric patients with ulcerative colitis (UC) are scarce. AIMS: To determine incidence, risk factors and clinical outcome of pouchitis following IPAA in children. METHODS: This multicenter, retrospective cohort study, included all pediatric UC patients who underwent colectomy and IPAA from January 2010 to December 2016. RESULTS: Eighty-five patients were enrolled. During a median post-surgical period of 24.8 (range: 1.0-72.0) months following IPAA, 38 (44.7%) patients developed pouchitis, including 6 (15.8%) who developed chronic pouchitis. Kaplan-Meier survival estimates of the cumulative probability for pouchitis were 14.6% at 1 year and 27.3% and 51.5% at 2 and 5 years, respectively. Multiple Cox regression model showed that older age at colectomy (hazard ratio, HR: 0.89, p = 0.008) was a protective factor, whereas chronic active colitis as indication for surgery (HR: 4.45, p < 0.001), and a 3-stage IPAA (HR: 2.86, p = 0.028) increased the risk for pouchitis. CONCLUSIONS: Long-term risk for pouchitis is significantly high in pediatric-onset UC after IPAA. Younger age at colectomy, chronic active colitis as indication for surgery and 3-stage IPAA may increase the risk for pouchitis.

Anastomotic ulcers in short bowel syndrome: New suggestions from a multidisciplinary approach.

BACKGROUND AND AIMS: Anastomotic ulceration (AU) is a rare potential life-threatening complication that may occur after intestinal resection. The diagnosis is often delayed after a long-lasting history of refractory anemia. The pathogenesis remains unknown and there are no established therapies. The aim of the study was to analyze the medical history of children with short bowel syndrome (SBS) who were experiencing AU. METHODS: Records of SBS children were retrospectively reviewed. Demographics, baseline characteristics, presentation, diagnosis and treatment of AU cases were analyzed. RESULTS: Eight out of 114 children with SBS were identified as having AU. Mean gestational age was 32.5weeks. Underlying diseases were: 5 necrotising enterocolitis, 2 gastroschisis and 1 multiple intestinal atresia. The mean age at AU diagnosis was 6.5years (diagnosis delay of 35months). All but 2 patients had AU persistency after medical treatment. Endoscopic treatment (2 argon plasma coagulation; 1 platelet-rich fibrin instillation; 2 endoscopic hydrostatic dilations) was effective in 3 out of 5 children. Surgery was required in 3 patients. CONCLUSIONS: Severe bowel ischemic injury, especially in preterm infant, could predispose to AU development. Medical treatment showed discouraging results. We firstly described that different endoscopic treatment could be attempted before resorting to further surgery. LEVEL OF EVIDENCE: IV.

Inflammatory bowel disease in chronic granulomatous disease: An emerging problem over a twenty years' experience.

BACKGROUND: Chronic granulomatous disease (CGD) is a primary immunodeficiency of phagocytes, characterized by life-threatening infections and hyperinflammation. Due to survival improvement, inflammatory bowel disease (IBD) is becoming increasingly relevant. Here, we report our 20 year experience. METHODS: We retrospectively analyzed clinic, endoscopic, and histologic features, as well as the management of CGD-IBD patients referred to the Bambino Gesù Children's Hospital in Rome, Italy. RESULTS: Of 20 patients with CGD, 9 presented with CGD-IBD at diagnosis and/or during follow-up. Symptoms occurred at a median age of 16 years (range 3.2-42), with a median delay of 6 months for endoscopic confirmation. Patients mainly complained of nonspecific diarrhea (55%), with discrepancy between symptom paucity and severe endoscopic appearance, mainly represented by extensive colonic involvement (44%). Histology revealed at least 2 characteristic features (epithelioid granulomas, pigmented macrophages, and increased eosinophils) in 78% of patients. Eight of 9 patients received oral mesalamine, and 5 required systemic steroids. One patient received azathioprine due to steroid dependence. No patient required biological therapy or surgery. Clinical remission was obtained in all patients, but the majority complained of mild relapses. Two episodes of severe infection occurred early after steroid therapy. CONCLUSIONS: Penetrance of CGD-IBD increases with age. Clinical manifestations may be subtle, and clinicians should have a low threshold to recommend endoscopy. Treatment with NSAIDs and/or steroids achieves a good response, but relapses usually occur. Infection surveillance is mandatory during treatment, to prevent opportunistic infections. A close collaboration between pediatric immunologists and gastroenterologists is pivotal, including combined follow-up.

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.