Efficacy and Safety of Teduglutide in Infants and Children With Short Bowel Syndrome Dependent on Parenteral Support.

OBJECTIVES: Our objective was to evaluate the short- and long-term safety and efficacy of teduglutide treatment in infants and children with short bowel syndrome with intestinal failure (SBS-IF). METHODS: Two open-label phase 3 studies and 1 extension study investigated the short- and long-term safety and efficacy of teduglutide (0.05 mg/kg/day) in infants and children with SBS-IF: NCT03571516, 24-week study of infants who were randomized to receive teduglutide or standard of care (SoC); NCT02980666, 24-week study of infants and children who all received teduglutide; and NCT03268811, 24-week extension study of patients who completed NCT02980666 (patients could receive up to 48 weeks of total treatment). RESULTS: Twelve infants and 8 children enrolled in the core studies, and 2 infants and 7 children in the extension study. After 24 weeks of treatment, parenteral support (PS) requirements reduced by ≥20% from baseline for 4 infants (57.1%) and 4 children (66.7%) receiving teduglutide and for 2 infants receiving SoC (50.0%). One infant (50.0%) and 4 children (80.0%) receiving teduglutide maintained the ≥20% reduction in PS at 48 weeks of treatment. Two children receiving teduglutide achieved enteral autonomy, after 12 weeks and 28 weeks of treatment, respectively. All adverse events (AEs) were in line with known impacts of SBS-IF and adverse reactions to teduglutide. Only one serious AE (abdominal pain) was considered related to teduglutide. CONCLUSIONS: Short- and long-term treatment with teduglutide resulted in clinically meaningful reductions in PS requirements for infants and children with SBS-IF. Teduglutide was well tolerated, and efficacy improved with longer-term treatment.

Applicability, efficacy, and safety of over-the-scope clips in children.

BACKGROUND AND AIMS: Over-the-scope clips (OTSCs) are now becoming popular in endoscopy performed in adults for indications such as acute nonvariceal GI bleeding, anastomotic bleeding, and for closure of gastrocutaneous and postgastrostomy fistulae. Varied sizes of clip are available, but even the smallest, 8.5 to 9.8 mm in diameter with its loading device on the tip of the endoscope, increases device and endoscope intubation diameters up to 14.65 mm. This may present challenges in terms of the size of the patient in whom it might be used. OTSCs appear to be effective and safe in the hands of those who are trained appropriately in endoscopy on adult patients; however, the experience of OTSC application in children is not reported. Here we present results of a service evaluation of this technology at 2 regional/national referral pediatric endoscopy units in the United Kingdom and the United States. METHODS: Two tertiary centers' databases were searched to identify cases in which OTSCs were used. Demographics, presentation, anthropometry, comorbidities, efficacy, adverse events, and postprocedure follow-up were recorded, with identification of resolution or recurrence. RESULTS: OTSC procedures were performed on 24 occasions in 20 patients (11 girls) between February 2018 and February 2021. Patients had a mean age of 12 years (range, 5-17) and a mean weight of 44.42 kg (range, 18.2-70.3). Indications were nonhealing PEG site fistulae (n = 7), acute nonvariceal upper GI bleeding (ANUGIB) from gastric ulcers (5), ANUGIB from duodenal ulcers (3), nonhealing bleeding anastomotic ulcer (3), esophageal mucocutaneous fistula (1), and gastric perforation (1). Technical success was achieved in all but 1 case (95%), and clinical success was achieved in 18 cases (90%). CONCLUSIONS: The OTSC device appears to be effective in children (minimum age 5 years and minimum weight 18 kg) in a limited number of situations including anastomotic ulcer, closure of leaking PEG site, gastric perforation, and bleeding peptic ulcers. The operator should be an experienced endotherapeutic endoscopist with specific OTSC training, and the type and size of the OTSC device should be carefully considered, along with any comorbidities of the patient that may preclude success and/or lead to potential adverse events such as esophageal perforation.

Colonoscope "Looping" During Ileo-Colonoscopy in Children is Significantly Different to that Observed in Adult Practice.

OBJECTIVES: Ileo-colonoscopy (IC) can be technically challenging because of unpredictable colonoscope loop formation. Aims of this study were to assess the risk of loop formation and to attempt to understand which factors were likely to predispose to which subtype of loop. METHODS: Prospective study conducted on children referred for an IC at Sheffield Children's Hospital. Presence and type of loop was objectively assessed using the magnetic endoscope imaging tool. RESULTS: Three hundred procedures were prospectively evaluated. Only 9% of paediatric ICs were loop-free. Alpha loops were the most common loop in children older than 5, whereas reverse alpha loops and a wider variety of complex and repetitive loops were observed in younger patients. Once a specific type of loop has formed, the risk of re-looping in a different way or in a different position of the colon is reduced. Left lateral starting position was found to increase the risk of reverse alpha loops and re-looping. Challenging loops, such as reverse alpha, were more frequent in males. Higher body mass index (BMI) was associated with an increased risk of alpha and deep transverse loops formation, while lower BMI with a higher incidence of reverse alpha and N loop. Loop formation did not prevent 100% ileal intubation. CONCLUSIONS: This study represents the first attempt to describe loop formation according to patient characteristics in a large paediatric series. Further studies are needed in order to establish if these findings could be helpful in simplifying the execution of IC procedures in children and facilitate the learning curve during endoscopy training programs.

Adaptations to the current ECCO/ESPGHAN guidelines on the management of paediatric acute severe colitis in the context of the COVID-19 pandemic: a RAND appropriateness panel.

OBJECTIVE: Paediatric acute severe colitis (ASC) management during the novel SARS-CoV-2/COVID-19 pandemic is challenging due to reliance on immunosuppression and the potential for surgery. We aimed to provide COVID-19-specific guidance using the European Crohn's and Colitis Organisation/European Society for Paediatric Gastroenterology, Hepatology and Nutrition guidelines for comparison. DESIGN: We convened a RAND appropriateness panel comprising 14 paediatric gastroenterologists and paediatric experts in surgery, rheumatology, respiratory and infectious diseases. Panellists rated the appropriateness of interventions for ASC in the context of the COVID-19 pandemic. Results were discussed at a moderated meeting prior to a second survey. RESULTS: Panellists recommended patients with ASC have a SARS-CoV-2 swab and expedited biological screening on admission and should be isolated. A positive swab should trigger discussion with a COVID-19 specialist. Sigmoidoscopy was recommended prior to escalation to second-line therapy or colectomy. Methylprednisolone was considered appropriate first-line management in all, including those with symptomatic COVID-19. Thromboprophylaxis was also recommended in all. In patients requiring second-line therapy, infliximab was considered appropriate irrespective of SARS-CoV-2 status. Delaying colectomy due to SARS-CoV-2 infection was considered inappropriate. Corticosteroid tapering over 8-10 weeks was deemed appropriate for all. After successful corticosteroid rescue, thiopurine maintenance was rated appropriate in patients with negative SARS-CoV-2 swab and asymptomatic patients with positive swab but uncertain in symptomatic COVID-19. CONCLUSION: Our COVID-19-specific adaptations to paediatric ASC guidelines using a RAND panel generally support existing recommendations, particularly the use of corticosteroids and escalation to infliximab, irrespective of SARS-CoV-2 status. Consideration of routine prophylactic anticoagulation was recommended.

Anastomotic Ulcers: A Tertiary Centre Experience of Endoscopic Management Techniques.

ABSTRACT: Improvements in neonatal care and surgical advances, has led to an increased prevalence of children with small and large bowel anastomoses. Ulceration at the site of anastomosis is a rare, but well-recognised phenomenon, with no clearly understood pathogenesis. Paediatric case series have been reported but there remains no clear effective treatment strategy and there is limited experience with endoscopic techniques in their management. We report our tertiary centre experience of managing nine anastomotic ulcer patients, including endoscopic treatment with argon plasma coagulation and clips.Two patients with inflammatory bowel disease (IBD) responded to optimisation of medical therapy. In our non-IBD patients, those requiring a blood transfusion (n = 2) ultimately required surgery and those who did not require a blood transfusion responded to aminosalicylate treatment (n = 1) or endoscopic therapeutic techniques (n = 3).We conclude that endoscopic interventions can be an effective management strategy for anastomotic ulcers when a blood transfusion isn't required.

The Use and Safety of a Novel Haemostatic Spray in the Endoscopic Management of Acute Nonvariceal Upper Gastrointestinal Bleeding in Children.

AIMS AND BACKGROUND: Advanced endohaemostatic technique performance and experience is extremely variable in distribution amongst paediatric endoscopists. Haemostatic spray (Hemospray), a novel endohaemostatic topically applied powder has the advantage of extreme ease of use and; hence may lower the threshold of competency required by the endoscopist thereby potentially reducing mortality. The aim of the study is to prospectively evaluate the efficacy and the safety of haemostatic spray in paediatric patients with acute upper gastrointestinal bleeding (AUGIB). METHODS: Prospective enrolment of children with AUGIB (Group 1) occurred, either as primary therapy or as an adjunct to standard endohaemostatic therapeutic techniques. Patients were assessed for likely need for endohaemostatic intervention of >8 of 24 of the paediatric Sheffield AUGIB score.A follow-up endoscopy occurred in those deemed to have clinical need pre-discharge. For comparison, another group (Group 2) of patients, who received conventional endohaemostatic treatment in the preceding 36 months, were reviewed. RESULTS: A total of 20 applications of Hemospray occurred in 17 patients (8 boys, median (range) age: 6.5 years (2 days to 17.75 years) and a total of 29 patients were enrolled in Group 2 (16 boys, median [range] age: 5.1 [0.25-17.0]). All patients tolerated haemostatic spray applications with no adverse events. The haemostatic spray group achieved 100% initial haemostasis with 18% rebleeding rate, although only a 6% failure rate after re-application. In the conventional group, similar 100% initial haemostasis was achieved with 24% rebleeding rate and 7% failure rate necessitating surgical interventions. CONCLUSIONS: This paediatric series suggests that monotherapy with haemostatic spray is as effective as conventional approaches in the management of AUGIB.

Effectiveness of Double-balloon Enteroscopy-facilitated Polypectomy in Pediatric Patients With Peutz-Jeghers Syndrome.

Sizable small-bowel (SB) polyps in Peutz-Jeghers syndrome (PJS) pose a high risk for intussusception, often necessitating laparotomy and intraoperative enteroscopy. This series examines the effectiveness of double-balloon enteroscopy (DBE) facilitated polypectomy for pediatric patients with PJS. Prospective analysis of collected data (6 years) on all patients with PJS referred for DBE-facilitated SB polypectomy at a pediatric tertiary-referral center. A total of 16 pediatric patients with PJS were referred for DBE-facilitated SB polypectomy. Twenty-two DBEs were performed. Large polyps (≥1 cm) were confirmed in 14 patients. Successful clearance of large SB polyps by DBE or laparoscopically assisted DBE (Lap-DBE) was achieved in all patients. One patient experienced post-Lap-DBE pelvic abscess. All other patients remained asymptomatic and intervention free throughout follow-up (median 26 months). This series demonstrates that DBE-facilitated polypectomy is an effective therapeutic option in pediatric patients with PJS. It should be considered at an early age where possible.

Diagnostic and therapeutic utility of double-balloon enteroscopy in children.

OBJECTIVES: Diagnostic and therapeutic benefits of double-balloon enteroscopy (DBE) have been documented in adults, with few data available on pediatric patients. We evaluated the diagnostic and therapeutic utility of DBE in children. METHODS: A prospective assessment of 113 DBE procedures in 58 consecutive children younger than 18 years (36 boys, 22 girls; median age 12.7 years, range 1-18 years) was performed for a variety of suspected small bowel (SB) disorders from January 2008 to August 2012 in a tertiary referral center for pediatric patients. All of the children had undergone upper gastrointestinal endoscopy and ileocolonoscopy. A total of 19 patients had undergone radiological investigations for SB (n = 11 magnetic resonance imaging; n = 5 barium enterography; n = 3 computed tomography) and 54 patients had undergone wireless capsule endoscopy (WCE). RESULTS: The overall median (range) examination time was 92.5 (45-275) minutes. The median (range) estimated insertion length of SB distal to pylorus was 230 (80-450) cm and proximal to ileocecal valve was 80 (5-275) cm. The common indications for DBE were polyposis syndromes (n = 21) and obscure gastrointestinal bleeding (n = 16). The findings included polyps (n = 19), mucosal ulcers and erosions (n = 8), submucosal elevations with white nodules (n = 4), and angioma/angiodysplasia (n = 2). The overall diagnostic yield for SB lesions using DBE was 70.7% (41/58) and for WCE was 77.7% (42/54). Endotherapeutic intervention was successfully used in 46.5% (n = 27/58). The endoscopic, medical, and surgical contributions to change in management by DBE were 72.4% (n = 42/58). Three complications (5.2%) were noted with uneventful recovery. CONCLUSIONS: The diagnostic yield of DBE was comparable to WCE, but with the addition of therapeutic possibility and histological yield. We believe this technique could be a valuable addition to existing endoscopic techniques, complementary to WCE, and may be considered as an alternative diagnostic and therapeutic option in the SB in children.

Follicular carcinoma of thyroid following successful liver transplantation--a report.

Follicular carcinoma of the thyroid is a relatively rare malignancy in childhood even in paediatric solid organ transplant recipients. The risk of developing de novo malignancies after liver transplantation is higher compared to the general population. We report an 18-yr-old girl who had successfully undergone liver transplantation five yr earlier for neonatal sclerosing cholangitis complicated by the development of dysplastic nodules. Baseline immunosuppression was with tacrolimus and prednisolone. Mycophenolate mofetil was later added in view of steroid-resistant episodes of graft rejection. She subsequently suffered from marked obesity and essential hypertension needing antihypertensive medication. Five yr after liver transplantation, she presented with a right-sided thyroid swelling that was rapidly progressive with no associated lymphadenopathy and normal systemic examination. Ultrasound of her neck revealed a solid lesion in the right lobe of the thyroid gland with ill-defined margins, and a diagnostic right thyroid lobectomy confirmed the diagnosis of follicular carcinoma with focal capsular and vascular invasion. She underwent total thyroidectomy and currently remains well on thyroxine supplements. Our report highlights the need for high level of suspicion and prompt investigation into any abnormal lesion in the long-term follow-up of solid organ transplant recipients.

Alterations of mucosa-attached microbiome and epithelial cell numbers in the cystic fibrosis small intestine with implications for intestinal disease.

Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Defective CFTR leads to accumulation of dehydrated viscous mucus within the small intestine, luminal acidification and altered intestinal motility, resulting in blockage. These changes promote gut microbial dysbiosis, adversely influencing the normal proliferation and differentiation of intestinal epithelial cells. Using Illumina 16S rRNA gene sequencing and immunohistochemistry, we assessed changes in mucosa-attached microbiome and epithelial cell profile in the small intestine of CF mice and a CF patient compared to wild-type mice and non-CF humans. We found increased abundance of pro-inflammatory Escherichia and depletion of beneficial secondary bile-acid producing bacteria in the ileal mucosa-attached microbiome of CFTR-null mice. The ileal mucosa in a CF patient was dominated by a non-aeruginosa Pseudomonas species and lacked numerous beneficial anti-inflammatory and short-chain fatty acid-producing bacteria. In the ileum of both CF mice and a CF patient, the number of absorptive enterocytes, Paneth and glucagon-like peptide 1 and 2 secreting L-type enteroendocrine cells were decreased, whereas stem and goblet cell numbers were increased. These changes in mucosa-attached microbiome and epithelial cell profile suggest that microbiota-host interactions may contribute to intestinal CF disease development with implications for therapy.

Celiac Plexus Block to Treat Refractory Feed Induced Dystonia in Children with Severe Neurodisability: A Single Center Case Series.

This observational study describes the procedure technique, safety outcomes, and patient responses to celiac plexus blockade (CPB) in children with severe neurodisability with refractory feed intolerance, feed induced pain or feed induced dystonia (FID). Method: A review of the pathophysiological response to feeding in children with significant neurodisability and the effect on the neuroenteric system. A 2-stage CT-guided temporary celiac plexus blockade followed by neurolysis technique is described. We compile a case series of 5 patients with life limiting conditions and significant disability undergoing CPB in a single tertiary pediatric hospital. Results: A total of 10 separate procedures in 5 children were completed. A positive outcome was observed in 3 out of 4 cases of pediatric FID. Two of the three patients on parenteral nutrition had improved feed tolerance postprocedure. All children tolerated the procedure well, no postprocedure complications were documented. Conclusions: In selected cases, children with life-threatening feed induced dystonia or effective intestinal failure can be safely treated with celiac plexus blockade when other therapies have failed.

Management of hyperplastic gastric polyp following upper gastrointestinal bleeding in infant with Menkes' disease.

We report a case of an infant with Menkes' disease (MD) presented at the age of five months, with coffee ground vomiting, melaena with a significant drop of haemoglobin. Urgent endoscopic assessment revealed a friable bleeding trans-pyloric multi-lobulated sessile polyp. Due to further significant upper gastrointestinal bleeding, polypectomy occurred. Endoscopic mucosal resection was performed with a grasp-and-snare technique using a dual channel operating gastroscope. Haemostasis was achieved by application of argon plasma coagulation where required. No perforation occurred. Repeated debridement was required 6 wk after which the growth was excised completely with no further blood transfusion required after that procedure. Histological examination confirmed ulcerated and inflamed hyperplastic polyp. We discuss our endoscopic technique and discuss the reported gastrointestinal manifestation of MD in the literature.