Megacystis-microcolon-intestinal hypoperistalsis syndrome: don't forget the bladder.

PURPOSE: Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) is a well described clinical condition, but reports are focused on microcolon and intestinal hypoperistalsis, while data on bladder management are scant. Aim of the study is to present urological concerns in MMIHS. METHODS: Retrospective evaluation of clinical data on urological management of MMIHS patients treated in the last 10 years. RESULTS: Six patients were enrolled (3 male, 3 female). Three girls had prenatal diagnosis of megacystis (1 vesicoamniotic shunt was placed). All patients had genetic diagnosis: 5 had ACTG2 gene mutations and 1 MYH11 mutation. All patients were addressed to our attention for urinary symptoms, such as urinary retention, urinary tract infections, acute renal injury. Two patients presented frequent stoma prolapses. All children underwent a complete urological evaluation, and then started a bladder management protocol (clean intermittent catheterization, via urethra or cystostomy-tube placement), with improvement of urinary infections, upper urinary tract dilation and stoma prolapses, if present. All patients had good renal function at last follow-up. CONCLUSION: We believe that MMIHS patients must be addressed soon and before onset of symptoms for a multidisciplinary evaluation, including an early assessment by a pediatric urologist expert in functional disorder, to preserve renal function at its best.

Oral Viscous Budesonide in Children With Eosinophilic Esophagitis After Repaired Esophageal Atresia: A Clinical Trial.

OBJECTIVES: A high prevalence of eosinophilic esophagitis (EoE) has been reported in children with repaired esophageal atresia (EA). Topical steroids proved to be an effective and safe therapy in EoE, although not approved in pediatrics. We report the results of the first clinical trial of oral viscous budesonide (OVB) performed in children with EoE after repaired esophageal atresia (EoE-EA). METHODS: This open-label, single-arm, phase 2 clinical trial with randomized pharmacokinetic sampling, was conducted at the Bambino Gesù Children's Hospital between September 2019 and June 2021. EoE-EA patients received an age-banded dose of OVB twice daily for 12 weeks and were endoscopically evaluated. The primary endpoint was the rate of patients achieving histological remission. Secondary endpoints included clinical and endoscopic benefit after treatment, and safety assessments. RESULTS: Eight consecutive EA-EoE patients were enrolled (median age 9.1 years, interquartile range 5.5). Of these, 5 received 0.8 mg and 3 received 1.0 mg twice daily of OVB. Histological remission was obtained in all but 1 patient (87.5%). The clinical score showed significant improvement at the end of treatment in all patients. No endoscopic features of EoE were found after treatment. No treatment-emergent adverse event occurred. CONCLUSION: OVB is an effective, safe, and well-tolerated formulation of budesonide for use in pediatric patients with EoE-EA.

Hematemesis in Infants: The First Evidence-Based Score to Predict the Need for Timely Endoscopy.

OBJECTIVES: Infantile acute upper gastrointestinal bleeding involves a decision for therapeutic intervention that most pediatricians first coming into contact with the patient are, not unreasonably, unable to objectively provide. Therefore, some objective tools of individual risk assessment would seem to be crucial. The principal aim of the present study was to investigate the anamnestic and clinical parameters of infants with hematemesis, together with laboratory and instrumental findings, to create a scoring system that may help identify those infants requiring an appropriate and timely application of upper gastrointestinal (GI) endoscopy. METHODS: Clinical data of infants admitted for hematemesis to the participating centers over the study period were systematically collected. According to the outcome dealing with rebleeding, need for blood transfusion, mortality, finding of GI bleeding lesions, or need for surgical intervention, patients were blindly divided into a group with major clinical severity and a group with minor clinical severity. Univariate and multivariate logistic regressions were conducted to investigate significant prognostic factors for clinical severity. RESULTS: According to our findings, we drafted a practical diagnostic algorithm and a clinical score able to predict the need for timely upper GI endoscopy (BLOVO infant score). Our clinical scoring system was created by incorporating anamnestic factors, clinical parameters, and laboratory findings that emerged as predictors of a worst outcome. CONCLUSIONS: We provided the first objective tool of individual risk assessment for infants with hematemesis, which could be very useful for pediatricians first coming into contact with the patient in the emergency department.

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.

New therapies for esophageal strictures in children.

PURPOSE OF REVIEW: The present review aims at describing recent advances in therapeutic strategies for the treatment of benign esophageal strictures in children. We discuss current knowledge and practice on esophageal dilations, which are still the mainstream of treatment. We present new evidence about adjuvant treatments for recurrent and refractory strictures, including endoscopic incisional therapy, esophageal stenting, intralesional or topical mytomicin C and intralesional, systemic or topical steroids. RECENT FINDINGS: Current evidence on esophageal dilations is not sufficient to establish superiority of one of the available techniques, especially the use of balloon or bougie dilators, but a prospective international cohort study on anastomotic stricture in esophageal atresia is underway to address this issue. Recurrent and refractory strictures still represent a challenge, since none of the adjuvant pharmacological and mechanical interventions has shown to be enough feasible, effective and safe to revolutionize clinical practice. SUMMARY: In the last couple of years, several encouraging results have been published on management of esophageal strictures in children. Further research is needed, hopefully directed toward secure, easily reproducible and minimally invasive measures.

An international survey on anastomotic stricture management after esophageal atresia repair: considerations and advisory statements.

BACKGROUND: Endoscopic dilatation is the first-line treatment of stricture formation after esophageal atresia (EA) repair. However, there is no consensus on how to perform these dilatation procedures which may lead to a large variation between centers, countries and doctor's experience. This is the first cross-sectional study to provide an overview on differences in endoscopic dilatation treatment of pediatric anastomotic strictures worldwide. METHODS: An online questionnaire was sent to members of five pediatric medical networks, experienced in treating anastomotic strictures in children with EA. The main outcome was the difference in endoscopic dilatation procedures in various centers worldwide, including technical details, dilatation approach (routine or only in symptomatic patients), and adjuvant treatment options. Descriptive statistics were performed with SPSS. RESULTS: Responses from 115 centers from 32 countries worldwide were analyzed. The preferred approach was balloon dilatation (68%) with a guidewire (66%), performed by a pediatric gastroenterologist (n = 103) or pediatric surgeon (n = 48) in symptomatic patients (68%). In most centers, hydrostatic pressure was used for balloon dilatation. The insufflation duration was standardized in 59 centers with a median duration of 60 (range 5-300) seconds. The preferred first-line adjunctive treatments in case of recurrent strictures were intralesional steroids and topical mitomycin C, in respectively 47% and 31% of the centers. CONCLUSIONS: We found a large variation in stricture management in children with EA, which confirms the current lack of consensus. International networks for rare diseases are required for harmonizing and comparing the procedures, for which we give several suggestions.

Update on chronic intestinal pseudo-obstruction.

PURPOSE OF REVIEW: Chronic intestinal pseudo-obstruction (CIPO) is the most severe and disabling form of gastrointestinal dysmotility characterized by an impairment of coordinated propulsive activity in the gastrointestinal tract mimicking mechanical intestinal obstruction. Over the last few years, major advances have been made in the diagnostic and therapeutic management of this rare disorder. RECENT FINDINGS: The present narrative review aims to summarize the current literature about the management of CIPO focusing on significant novelties about definition, epidemiology, diagnosis, and therapeutic options. The most significant advancement is a consensus on classification and dedicated diagnostic criteria for CIPO in children highlighting the distinctive features between adult and pediatric forms of CIPO (hence pediatric intestinal pseudo-obstruction). Despite no single diagnostic test is pathognomonic of CIPO and no recommended drug treatment is advised to improve gastrointestinal motility, recent reports suggest promising results in both diagnostic testing and therapy that might assist the diagnosis and help the management of patients with CIPO. SUMMARY: The articles referenced in this review will help in optimizing the clinical management of this rare and severe disease in adult population.

Association between body positioning and gastroesophageal reflux in paediatric age.

AIM: 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. METHODS: We retrospectively assessed the pH-impedance parameters of paediatric patients referred for possible GER-related symptoms to two hospitals in Naples and Rome, Italy, from September 2016 to September 2018. Data were separately obtained for the time that the patients spent in upright and recumbent positions. RESULTS: Data from 187 patients under the age of 18 were collected, at a mean age of just over seven years. We found that the acid exposure time was stable irrespective of changes in body position (P > .05). The mean number of reflux episodes per hour was 2.99 during the upright position and 1.21 during the recumbent position (P < .05), and the mean oesophageal acid clearance time was 44.4 and 93.4 seconds, respectively (P < .05). CONCLUSION: Most paediatric patients experienced reflux in the upright rather than recumbent position, probably as a result of frequent transient lower oesophageal sphincter relaxations while they were awake. In particular, our findings provide new insights into postural measures for reflux in children and adolescents.

Association Between Obesity/Overweight and Functional Gastrointestinal Disorders in Children.

OBJECTIVE: Although emerging data indicate that obese/overweight children are more likely to develop functional gastrointestinal disorders (FGIDs) than normal-weight peers, contrasting results have been reported. The present observational, case-control study aimed at estimating the prevalence of FGIDs in obese/overweight children compared to normal-weight peers. METHODS: Consecutive obese and overweight children aged 4 to 18 years attending the obesity outpatient clinic were enrolled as study cases. Normal-weight children were enrolled as comparison group. All the enrolled patients received a thorough health examination from both a pediatric endocrinologist and gastroenterologist. Moreover, they were asked to fill out the Rome III questionnaire for the diagnosis of FGIDs. Data were analyzed to compare the prevalence of FGIDs between cases and controls. RESULTS: Throughout the study period we enrolled 103 cases and 115 controls. No significant age and sex differences were found between the 2 groups. FGIDs were significantly more prevalent in obese/overweight compared to normal-weight children (47.57% vs 17.39%; P < 0.0001). Increased prevalence was observed for functional constipation (18.44% vs 7.82%; P = 0.025), functional dyspepsia (23.33% vs 6.95%; P = 0.001), and irritable bowel syndrome (10.67% vs 2.60%; P = 0.024), whereas no difference was observed for functional abdominal pain (1.94% vs 2.60%; P = 1.00). CONCLUSIONS: Our data suggest that there is a link between excess body fat and FGIDs in children. This finding may offer a model of patients in which the effects of food and nutritional substances, the gut microbial environment, and psychosocial factors are fitting well with the emerging biopsychosocial conceptual model for FGIDs.

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 experiences 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. During 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.

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.

Effect of Bowel Cleansing on Colonic Transit Time Measurement in Children with Chronic Constipation.

We evaluated the effect of bowel preparation on colonic transit time (CTT) measured by the radio-opaque marker test in children with constipation. All children underwent 2 radio-opaque marker-CTT tests, both in cleansed and uncleansed bowel state. Our findings confirm that the state of colonic fecal filling may significantly influence CTT.

Clinical relevance of esophageal baseline impedance measurement: just an innocent bystander.

OBJECTIVE: The clinical relevance of esophageal baseline impedance (BI) remains to be determined. In the present study, we explored the impact of gastroesophageal reflux disease (GERD) and esophageal dysmotility on BI. METHODS: A total of 18 children with esophageal atresia, 26 children with GERD, and 17 controls prospectively underwent esophagogastroduodenoscopy and pH-impedance monitoring. BI was measured in both proximal and distal esophagus. Gastroesophageal reflux (GER) and bolus transit indicators were defined according to published criteria. RESULTS: Patients with esophageal atresia showed significantly lower proximal and distal BI values (952 [716-1811] Ω; 895 [284-1189] Ω; respectively) compared with those with GERD (3015 [2368-3975] Ω; 2231 [1770-3032] Ω, P < 0.001 and <0.001, respectively) and controls (3699 [3194-4358] Ω; 3522 [2927-3994] Ω, P < 0.001 and <0.001, respectively). Using linear regression, proximal BI strongly correlated with total bolus transit time (r(2) = 0.61, P < 0.001) and bolus presence time (BPT; r(2) = 0.63, P < 0.001). Distal BI weakly correlated with acid exposure time (r(2) = 0.16, P < 0.01) and longstanding reflux episodes (r(2) = 0.17, P < 0.01), and strongly correlated with total bolus transit time (r(2) = 0.53, P < 0.001) and BPT (r(2) = 0.58, P < 0.001). By logistic regression, BPT predicted low proximal BI values (odds ratio [OR] 1.052; P < 0.05), whereas both GER indicators (acid exposure time: OR 1.56, P < 0.05; longstanding reflux episodes: OR 2.8, P < 0.05) and BPT (OR 1.66, P < 0.01) predicted low distal BI values. CONCLUSIONS: Along the length of esophagus, both bolus transit variables and GER significantly affect BI. This suggests that BI may merely mirror phenomena occurring within the esophageal lumen or wall, limiting its value as a discrete clinical entity to replace variables already used for assessing both GERD and esophageal dysmotility.

Vernal keratoconjunctivitis and eosinophilic esophagitis: A rare combination?

Vernal keratoconjunctivitis (VKC) is a bilateral ocular inflammatory disease with a conjunctival and corneal involvement and typical onset during childhood. Eosinophilic esophagitis (EoE) is a chronic disease characterized by eosinophilic inflammation of the mucosa (≥15 eosinophils/HPF) and symptoms of esophageal dysfunction. EoE and VKC are both immune-mediated diseases sharing a similar pathogenetic mechanism and a high association with other allergic diseases. Nevertheless, no data are currently available about their clinical association. We present 4 cases of concomitant diagnosis of vernal keratoconjunctivitis and eosinophil esophagitis suggesting that these conditions may coexist in the same patient more frequently than expected. Health care providers should be aware of the possibility of co-occurrence in their daily practice.

Diagnostic and therapeutic approach to children with chronic refractory constipation: Consensus report by the SIGENP motility working group.

Constipation is a common problem in children, accounting for about 3% of all primary care visits and up to 25% of referrals to paediatric gastroenterologists. Although polyethylene glycol often proves effective, most children require prolonged treatment and about 50% of them have at least one relapse within the first 5 years after initial recovery. When conventional treatment fails, children are considered to have refractory constipation. Children with refractory constipation deserve specialist management and guidance. Over the last decades, 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. The present review analyses the possible diagnostic investigations for children with refractory constipation, focusing on their actual indications and their utility in clinical practice. Moreover, we have also analytically reviewed medical and surgical therapeutic options, which should be considered in selected patients in order to achieve the best clinical outcome.

Italian guidelines for the management of irritable bowel syndrome in children and adolescents : Joint Consensus from the Italian Societies of: Gastroenterology, Hepatology and Pediatric Nutrition (SIGENP), Pediatrics (SIP), Gastroenterology and Endoscopy (SIGE) and Neurogastroenterology and Motility (SINGEM).

The irritable bowel syndrome (IBS) is a functional gastrointestinal disorder (FGID), whose prevalence has widely increased in pediatric population during the past two decades. The exact pathophysiological mechanism underlying IBS is still uncertain, thus resulting in challenging diagnosis and management. Experts from 4 Italian Societies participated in a Delphi consensus, searching medical literature and voting process on 22 statements on both diagnosis and management of IBS in children. Recommendations and levels of evidence were evaluated according to the grading of recommendations, assessment, development, and evaluation (GRADE) criteria. Consensus was reached for all statements. These guidelines suggest a positive diagnostic strategy within a symptom-based approach, comprehensive of psychological comorbidities assessment, alarm signs and symptoms' exclusion, testing for celiac disease and, under specific circumstances, fecal calprotectin and C-reactive protein. Consensus also suggests to rule out constipation in case of therapeutic failure. Conversely, routine stool testing for enteric pathogens, testing for food allergy/intolerance or small intestinal bacterial overgrowth are not recommended. Colonoscopy is recommended only in patients with alarm features. Regarding treatment, the consensus strongly suggests a dietary approach, psychologically directed therapies and, in specific conditions, gut-brain neuromodulators, under specialist supervision. Conditional recommendation was provided for both probiotics and specific fibers supplementation. Polyethylene glycol achieved consensus recommendation for specific subtypes of IBS. Secretagogues and 5-HT4 agonists are not recommended in children with IBS-C. Certain complementary alternative therapies, antispasmodics and, in specific IBS subtypes, loperamide and rifaximin could be considered.

Pharmacokinetic Evaluation of Oral Viscous Budesonide in Paediatric Patients with Eosinophilic Oesophagitis in Repaired Oesophageal Atresia.

Eosinophilic oesophagitis is a long-term complication of oesophageal atresia (EA), an uncommon condition that affects approximately 1 in 3500 infants. An exploratory, open-label phase 2 clinical trial was conducted in paediatric eosinophilic oesophagitis after oesophageal atresia (EoE-EA) to assess the safety, pharmacokinetics, and efficacy of oral viscous budesonide (OVB). In total, eight patients were enrolled in the study and assigned to a twice-daily dosing regimen of either 0.8 or 1 mg OVB, depending on age and height, administered for 12 weeks. OVB was safe and effective in the treatment of EoE-EA. The current investigation focuses on the pharmacokinetics of budesonide and the impact of an oral viscous formulation on its absorption and bioavailability. Using a non-linear mixed effects approach, two distinct absorption profiles were identified, despite marked interindividual variability in drug concentrations. Budesonide exposure was higher than previously reported in children following oral inhalation. Even though no significant effect has been observed on serum cortisol levels, future studies should consider exploring different doses, schedules, and/or treatment durations, as there may be an opportunity to reduce the risk of cortisol suppression.