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Introduction:  The aims of the study are to systematically assess and critically appraise the evidence concerning two surgical techniques to lengthen the bowel in children with short bowel syndrome (SBS), namely, the longitudinal intestinal lengthening and tailoring (LILT) and serial transverse enteroplasty (STEP), and to identify patient characteristics associated with a favorable outcome.Materials and Methods:  MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched from inception till December 2019. No language restriction was used.Results:  In all, 2,390 articles were found, of which 40 were included, discussing 782 patients. The median age of the patients at the primary bowel lengthening procedure was 16 months (range: 1-84 months). Meta-analysis could not be performed due to the incomparability of the groups, due to heterogeneous definitions and outcome reporting. After STEP, 46% of patients weaned off parenteral nutrition (PN) versus 52% after LILT. Mortality was 7% for STEP and 26% for LILT. Patient characteristics predictive for success (weaning or survival) were discussed in nine studies showing differing results. Quality of reporting was considered poor to fair.Conclusion:  LILT and STEP are both valuable treatment strategies used in the management of pediatric SBS. However, currently it is not possible to advise surgeons on accurate patient selection and to predict the result of either intervention. Homogenous, prospective, outcome reporting is necessary, for which an international network is needed. [ABSTRACT FROM AUTHOR]

Infants developing necrotizing enterocolitis (NEC) have a different metabolomic profile compared to controls. The potential of specific metabolomics, i.e. amino acids and amino alcohols (AAA), as early diagnostic biomarkers for NEC is largely unexplored. In this multicenter prospective case–control study, longitudinally collected fecal samples from preterm infants (born <30 weeks of gestation) from 1–3 days before diagnosis of severe NEC (Bell's stage IIIA/IIIB), were analyzed by targeted high-performance liquid chromatography (HPLC). Control samples were collected from gestational and postnatal age-matched infants. Thirty-one NEC cases (15 NEC IIIA;16 NEC IIIB) with 1:1 matched controls were included. Preclinical samples of infants with NEC were characterized by five increased essential amino acids—isoleucine, leucine, methionine, phenylalanine and valine. Lysine and ethanolamine ratios were lower prior to NEC, compared to control samples. A multivariate model was rendered based on isoleucine, lysine, ethanolamine, tryptophan and ornithine, modestly discriminating cases from controls (AUC 0.67; p < 0.001). Targeted HPLC pointed to several specific AAA alterations in samples collected 1–3 days before NEC onset, compared to controls. Whether this reflects metabolic alterations and has a role in early biomarker development for NEC, has yet to be elucidated. [ABSTRACT FROM AUTHOR]

Background: Colonic manometry is the current reference standard for assessing colonic neuromuscular function in children with intractable functional constipation (FC). Recently, cine magnetic resonance imaging (cine-MRI) has been proposed as a non-invasive alternative. We compared colonic motility patterns on cine-MRI with those obtained by manometry in children, by stimulating high-amplitude propagating contractions (HAPCs) with bisacodyl under manometric control while simultaneously acquiring cine-MRI. Methods: After Institutional Review Board approval, adolescents with FC scheduled to undergo colonic manometry were included. A water-perfused 8-lumen catheter was used for colonic manometry recordings. After an intraluminal bisacodyl infusion, cine-MRI sequences of the descending colon were acquired for about 30 min simultaneously with colonic manometry. Manometry recordings were analysed for HAPCs. MRI images were processed with spatiotemporal motility MRI techniques. The anonymised motility results of both techniques were visually compared for the identification of HAPCs in the descending colon. Results: Data regarding six patients (three males) were analysed (median age 14 years, range 12–17). After bisacodyl infusion, three patients showed a total of eleven HAPCs with colonic manometry. Corresponding cine-MRI recorded high colonic activity during two of these HAPCs, minimal activity during seven HAPCs, while two HAPCs were not recorded. In two of three patients with absent HAPCs on manometry, colonic activity was recorded with cine-MRI. Conclusions: Simultaneous acquisition of colonic cine-MRI and manometry in children with FC is feasible. Their motility results did not completely overlap in the identification of HAPCs. Research is needed to unravel the role of cine-MRI in this setting. [ABSTRACT FROM AUTHOR]

Purpose of review: Functional constipation (FC) in children is a common health problem with reported worldwide prevalence rates up to 32.2%. The majority of children with constipation respond to oral laxative treatment. After 5 years of intensive treatment, however, approximately 50% of children remain symptomatic. To discuss the evidence for new treatments in these children, including pre- and probiotics, pelvic physiotherapy, prucalopride, sacral nerve stimulation, and surgery, and to highlight the controversies surrounding them. Recent findings: Pre- and probiotics and prucalopride are not effective in the treatment of childhood constipation. Pelvic physiotherapy and sacral nerve stimulation are promising treatment options but larger trials are needed. Surgery for pediatric constipation is the treatment of last resort. Summary: Large, well-designed placebo-controlled trials with proper outcome measures, as suggested by the Rome foundation pediatric subcommittee on clinical trials, are necessary to provide more insight regarding the efficacy of new treatments in childhood constipation. [ABSTRACT FROM AUTHOR]

Abstract: Background: Using water‐perfused (WP) high‐resolution manometry, we recently demonstrated that children with functional constipation (FC) lacked the postprandial increase in distal colonic cyclic motor patterns that was observed in healthy adults. Our aim was to determine if similar results could be detected using a solid‐state (SS) manometry catheter. Methods: We performed a retrospective analysis of 19 children with FC (median age 11.1 years, 58% male) who underwent colonic manometry with a SS catheter (36 sensors, 3 cm apart). Data were compared with previously published data using a WP catheter (36 sensors, 1.5 cm apart) recorded from 18 children with FC (median age 15 years; 28% male). Key Results: The cyclic motor patterns recorded by the SS catheter did not differ from those previously recorded by the WP catheter. There was no detected increase in this activity in response to the meal in either group. Long‐single motor patterns were recorded in most patients (n = 16, 84%) with the SS catheter. The number of these events did not differ from the WP recordings. In the SS data, HAPCs were observed in 4 children prior to the meal, in 5 after the meal. This did not differ significantly from the WP data. Conclusions & Inferences: These data recorded by SS manometry did not differ from WP manometry data. Regardless of the catheter used, both studies revealed an abnormal colonic response to a meal, indicating a pathology which is not related to the catheter used to record these data. [ABSTRACT FROM AUTHOR]

Background & aims: Intestinal microbiota is considered to play a crucial role in the aetiology of inflammatory bowel disease (IBD). We aimed to describe faecal microbiota composition and dynamics in a large cohort of children with de novo (naïve) IBD, in comparison to healthy paediatric controls (HC). Methods: In this prospective study, performed at two tertiary centres, faecal samples from newly diagnosed, treatment-naïve paediatric IBD patients were collected prior to bowel cleansing for colonoscopy (t0) and 1, 3 and 6 weeks and 3 months after initiation of therapy. The microbial profiles of Crohn’s disease (CD) and Ulcerative colitis (UC) patients were compared with HC and linked to therapeutic response. Microbiota composition was analysed by IS-pro technology. Results: Microbial profiles of 104 new IBD-patients (63 CD, 41 UC, median age 14.0 years) were compared to 61 HC (median 7.8 years). IBD was mainly characterised by decreased abundance of Alistipes finegoldii and Alistipes putredinis, which characterize a healthy state microbial core. The classifier including these core species as predictors achieved an AUC of the ROC curve of .87. Core bacteria tended to regain abundance during treatment, but did not reach healthy levels. Conclusion: Faecal microbiota profiles of children with de novo CD and UC can be discriminated from HC with high accuracy, mainly driven by a decreased abundance of species shaping the microbial core in the healthy state. Paediatric IBD can therefore be characterized by decreased abundance of certain bacterial species reflecting the healthy state rather than by the introduction of pathogens. [ABSTRACT FROM AUTHOR]

Abstract: Background: Evidence for the efficacy of commonly used drugs in the treatment of childhood functional constipation (FC) is scarce, studies are often of low quality and study designs are heterogeneous. Thus, recommendations for the design of clinical trials in childhood FC are needed. Purpose: Members of the Rome Foundation and a member of the Pediatric Committee of the European Medicines Agency formed a committee to create recommendations for the design of clinical trials in children with FC. Key Recommendations: This committee recommends conducting randomized, double‐blind, placebo‐controlled, parallel‐group clinical trials to assess the efficacy of new drugs for the treatment of childhood FC. Pediatric study participants should be included based on fulfilling the Rome IV criteria for FC. A treatment free run‐in period for baseline assessment is recommended. The trial duration should be at least 8 weeks. Treatment success is defined as no longer meeting the Rome IV criteria for FC. Stool consistency should be reported based on the Bristol Stool Scale. Endpoints of drug efficacy need to be tailored to the developmental age of the patient population. [ABSTRACT FROM AUTHOR]

Abstract: Background: Decreased sensation of urge to defecate is often reported by children with functional constipation (FC) and functional nonretentive fecal incontinence (FNRFI). The aim of this cross‐sectional study was to evaluate cerebral activity in response to rectal distension in adolescents with FC and FNRFI compared with healthy controls (HCs). Methods: We included 15 adolescents with FC, 10 adolescents with FNRFI, and 15 young adult HCs. Rectal barostat was performed prior to functional magnetic resonance imaging (fMRI) to determine individual pressure thresholds for urge sensation. Subjects received 2 sessions of 5 × 30 seconds of barostat stimulation during the acquisition of blood oxygenation level‐dependent fMRI. Functional magnetic resonance imaging signal differences were analyzed using SPM8 in Matlab. Key Results: Functional constipation and FNRFI patients had higher thresholds for urgency than HCs (P < .001). During rectal distension, FC patients showed activation in the anterior cingulate cortex, dorsolateral prefrontal cortex, inferior parietal lobule, and putamen. No activations were observed in controls and FNRFI patients. Functional nonretentive fecal incontinence patients showed deactivation in the hippocampus, parahippocampal gyrus, fusiform gyrus (FFG), lingual gyrus, posterior parietal cortex, and precentral gyrus. In HCs, deactivated areas were detected in the hippocampus, amygdala, FFG, insula, thalamus, precuneus, and primary somatosensory cortex. In contrast, no regions with significant deactivation were detected in FC patients. Conclusions & Inferences: Children with FC differ from children with FNRFI and HCs with respect to patterns of cerebral activation and deactivation during rectal distension. Functional nonretentive fecal incontinence patients seem to resemble HCs when it comes to brain processing of rectal distension. [ABSTRACT FROM AUTHOR]

Abstract: Aim: Sacral neuromodulation (SNM) is a minimally invasive therapy for functional constipation (FC) and is most often used to treat adults. Recent studies suggest that SNM may also beneficial in children. However, comparative data regarding preferred age of SNM for FC are lacking. Therefore, long‐term results of SNM for FC were compared between children and adults. Method: All patients treated with SNM for FC between 2004 and 2015 were evaluated. Outcomes of children (age 10–18 years) were compared with those for adults (≥ 18 years). The primary end‐point was a defaecation frequency of three or more times per week, which is consistent with the ROME‐III criteria. Secondary outcomes were quality of life (QoL; SF‐36) and the Cleveland Clinic Constipation Score. Results: One hundred and eighty patients (45 children, 135 adults) were eligible for SNM. The mean age was 15.8 (children) and 41.4 years (adults). One hundred and twenty‐six patients received permanent SNM (38 children, 88 adults). Mean follow‐up was 47 months in both groups. Defaecation frequency increased in both groups after SNM compared with baseline. Defaecation frequency in adults was higher than in children. The increased defaecation frequency was maintained during the entire follow‐up period in both groups. QoL of children was impaired compared with the Dutch population with regard to bodily pain, general health and vitality. Adults had worse QoL with regard to physical functioning, bodily pain, general health, vitality and social functioning compared with the Dutch population. QoL of children did not differ from adults. Conclusion: Sacral neuromodulation (SNM) should be considered in children (< 18 years) with FC. However, the indication of SNM for FC remains debatable considering the limited improvements and high costs. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To evaluate the long‐term efficacy of sacral nerve stimulation (SNS) in children with constipation and describe patient benefit and parent satisfaction. Methods: Using a prospective patient registry, we identified patients <21 years old with constipation treated with SNS for >2 years. We compared symptoms, medical treatment, PedsQL Gastrointestinal Symptom Scale (GSS), Fecal Incontinence Quality of Life Scale (FIQL), and Fecal Incontinence Severity Index (FISI) before SNS and at follow‐up. We contacted parents to administer the Glasgow Children's Benefit Inventory (GCBI) and a parent satisfaction questionnaire. Key Results: We included 25 children (52% male, median age 10 years): 16 had functional constipation, six anorectal malformation, two tethered spinal cord, and one Hirschsprung's disease. Defecation frequency did not change after SNS but patients reporting fecal incontinence decreased from 72% to 20% (P<.01) and urinary incontinence decreased from 56% to 28% (P=.04). Patients using laxatives decreased from 64% to 44% (ns) and patients using antegrade enemas decreased from 48% to 20% (P=.03). GSS, most FIQL domains, and FISI were improved at follow‐up. Six (24%) patients had complications requiring further surgery. Of the 16 parents contacted, 15 (94%) parents indicated positive health‐related benefit and all would recommend SNS to other families. Conclusions & Inferences: Sacral nerve stimulation is a promising and durable treatment for children with refractory constipation, and appears particularly effective in decreasing fecal incontinence. Although a quarter of patients experienced complications requiring additional surgery, nearly all parents reported health‐related benefit. Future studies to identify predictors of treatment response and complications are needed. [ABSTRACT FROM AUTHOR]

Aim This study aimed to assess the cost-effectiveness of sacral neuromodulation ( SNM) compared with conservative treatment in children and adolescents with constipation refractory to conservative management. Method A Markov probabilistic model was used, comparing costs and effectiveness of SNM and conservative treatment in children and adolescents aged 10-18 years with constipation refractory to conservative management. Input for the model regarding transition probabilities, utilities and healthcare costs was based on data from a cohort of patients treated in our centre. This cohort consisted of 30 female patients (mean age 16 years) with functional constipation refractory to conservative management. The mean duration of laxative use in this group was 5.9 years. All patients had a test SNM, followed by a permanent SNM in 27/30. Median follow-up was 22.1 months (range 12.2-36.8). The model was run to simulate a follow-up period of 3 years. Results The mean cumulative costs for the SNM group and the conservative treatment group were €17 789 ( SD €2492) and €7574 ( SD €4332) per patient, respectively. The mean quality adjusted life years ( QALYs) in the SNM group was 1.74 ( SD 0.19), compared with 0.86 ( SD 0.14) in the conservatively managed group. The mean incremental cost-effectiveness ratio was €12 328 per QALY ( SD €4788). Sensitivity analysis showed that the outcomes were robust to a wide range of model assumptions. Conclusion Chronic constipation seriously affects the quality of life of children and adolescents. Preliminary evidence suggests that SNM can improve symptoms and quality of life at a reasonable cost. [ABSTRACT FROM AUTHOR]

Background Subtyping achalasia by high-resolution manometry ( HRM) is clinically relevant as response to therapy and prognosis have shown to vary accordingly. The aim of this study was to assess inter- and intrarater reliability of diagnosing achalasia and achalasia subtyping in children using the Chicago Classification ( CC) V3.0. Methods Six observers analyzed 40 pediatric HRM recordings (22 achalasia and 18 non-achalasia) twice by using dedicated analysis software (ManoView 3.0, Given Imaging, Los Angeles, CA, USA). Integrated relaxation pressure ( IRP4s), distal contractile integral ( DCI), intrabolus pressurization pattern ( IBP), and distal latency ( DL) were extracted and analyzed hierarchically. Cohen's κ (2 raters) and Fleiss' κ (>2 raters) and the intraclass correlation coefficient ( ICC) were used for categorical and ordinal data, respectively. Results Based on the results of dedicated analysis software only, intra- and interrater reliability was excellent and moderate (κ=0.89 and κ=0.52, respectively) for differentiating achalasia from non-achalasia. For subtyping achalasia, reliability decreased to substantial and fair (κ=0.72 and κ=0.28, respectively). When observers were allowed to change the software-driven diagnosis according to their own interpretation of the manometric patterns, intra- and interrater reliability increased for diagnosing achalasia (κ=0.98 and κ=0.92, respectively) and for subtyping achalasia (κ=0.79 and κ=0.58, respectively). Conclusions Intra- and interrater agreement for diagnosing achalasia when using HRM and the CC was very good to excellent when results of automated analysis software were interpreted by experienced observers. More variability was seen when relying solely on the software-driven diagnosis and for subtyping achalasia. Therefore, diagnosing and subtyping achalasia should be performed in pediatric motility centers with significant expertise. [ABSTRACT FROM AUTHOR]

Background Studies comparing the outcome of ileal pouch-anal anastomosis (IPAA) in children and adults are scarce. This complicates decision-making in young patients. The aim of this study was to compare adverse events and pouch function between children and adults who underwent IPAA. Methods This cross-sectional cohort study included all consecutive children (aged less than 18 years) and adults with a diagnosis of inflammatory bowel disease or familial adenomatous polyposis who underwent IPAA in a tertiary referral centre between 2000 and 2015. Adverse events were assessed by chart review, and pouch function by interview using a pouch function score (PFS). Results In total, 445 patients underwent IPAA: 41 children (median age 15 years) and 404 adults (median age 39 years), with a median follow-up of 22 (i.q.r. 8-68) months. Being overweight ( P = 0·001), previous abdominal surgery ( P = 0·018), open procedures ( P < 0·001) and defunctioning ileostomy ( P = 0·014) were less common among children than adult patients. The occurrence of anastomotic leakage, surgical fistulas, chronic pouchitis and Crohn's of the pouch was not associated with paediatric age at surgery, nor was pouch failure. The development of anastomotic strictures was associated with having IPAA surgery during childhood (odds ratio 4·22, 95 per cent c.i. 1·13 to 15·77; P = 0·032). Pouch function at last follow-up was similar in the children and adult groups (median PFS 5·0 versus 6·0 respectively; P = 0·194). Conclusion Long-term pouch failure rates and pouch function were similar in children and adults. There is no need for a more cautious attitude to use of IPAA in children based on concerns about poor outcome. [ABSTRACT FROM AUTHOR]

Background Colonic dilation is common in children with intractable functional constipation ( FC). Our aim was to describe the association between segmental colonic dilation and colonic dysmotility in children with FC. Methods We performed a retrospective study on 30 children with intractable FC (according to the Rome III criteria) who had undergone colonic manometry and contrast enema within a 12-month time period. Colonic diameter was measured at 5 cm intervals from the anal verge up to the splenic flexure. Moreover, the distance between the lateral margins of the pedicles of vertebra L2 was measured to provide a ratio (colonic diameter or length/distance between the lateral margins; 'standardized colon size' [ SCS]). All manometry recordings were visually inspected for the presence of high-amplitude propagating contractions ( HAPCs); a parameter for colonic motility integrity. The intracolonic location of the manometry catheter sensors was assessed using an abdominal X-ray. Key Results Colonic segments with HAPCs had a significantly smaller median diameter than colonic segments without HAPCs (4.08 cm vs 5.48 cm, P<.001; SCS 1.14 vs 1.66, P=.001). Children with prematurely terminating HAPCs had significantly larger SCS ratios for colonic diameter than children with fully propagating HAPCs ( P=.008). SCS ratios for the length of the rectosigmoid and the descending colon and the SCS ratio for sigmoid colon diameter were significantly larger in children with FC compared to a previously described normative population ( P<.0001, P<.0001 and P=.0007 respectively). Conclusions & Inferences Segmental colonic dilation was associated with prematurely terminating HAPCs and may be a useful indicator of colonic dysmotility. [ABSTRACT FROM AUTHOR]

Background Children with intractable functional constipation ( FC) may eventually require surgery. However, guidelines regarding the surgical management of children with intractable FC are lacking. The aim of this study was to describe the surgical management of FC in children. Methods A retrospective chart review was performed of children with FC (according to the Rome III criteria) who underwent ileostomy, colostomy or (sub)total colectomy at a tertiary hospital. Treatment success was defined as no longer fulfilling the Rome III- FC-criteria or having a functional ostomy. In addition, a self-developed questionnaire was administered to parents by telephone to assess postsurgical satisfaction (yes-no question and rated on a scale of 1-10). Key Results Thirty-seven patients (68% female) were included; median age at first surgery was 12 years (range 1.6-17.6). The initial surgical procedure consisted of ileostomy (n=21), colostomy (n=10), sigmoid resection (n=5) and subtotal colectomy (n=1). Success criteria were fulfilled by 85% of the patients. Postsurgical satisfaction of parents was 91% with a median postoperative satisfaction score of 8 (range 2-10), and 97% would opt for the same procedure(s) if necessary. Thirty patients (81%) experienced stoma problems, with 12 patients (32%) requiring stoma-revisions. Other complications occurred in 16 patients (43%). Conclusions & Inferences Surgery can improve symptoms in children with intractable FC. Despite morbidity and complications, parental satisfaction is high. Prospective, high-quality research is necessary to develop guidelines for the diagnostic work-up and surgical management in children with intractable FC. [ABSTRACT FROM AUTHOR]

Background Rumination syndrome is characterized by recurrent regurgitation of recently ingested food into the mouth. Differentiation with other diagnoses and gastroesophageal reflux disease ( GERD) in particular, is difficult. Recently, objective pH-impedance ( pH- MII) and manometry criteria were proposed for adults. The aim of this study was to determine diagnostic ambulatory pH- MII and manometry criteria for rumination syndrome in children. Methods Clinical data and 24-hour pH- MII and manometry recordings of children with a clinical suspicion of rumination syndrome were reviewed. Recordings were analyzed for retrograde bolus flow extending into the proximal esophagus. Peak gastric and intraesophageal pressures closely related to these events were recorded and checked for a pattern compatible with rumination. Events were classified into primary, secondary, and supragastric belch-associated rumination. Key Results Twenty-five consecutive patients (11 males, median age 13.3 years [ IQR 5.9-15.8]) were included; recordings of 18 patients were suitable for analysis. Rumination events were identified in 16/18 patients, with 50% of events occurring <30 minutes postprandially. Fifteen of 16 patients showed ≥1 gastric pressure peak >30 mmHg, while only 50% of all events was characterized by peaks >30 mmHg and an additional 20% by peaks >25 mmHg. Four patients had evidence of acid GERD, all showing secondary rumination. Conclusions and Inferences Combined 24-hour pH- MII and manometry can be used to diagnose rumination syndrome in children and to distinguish it from GERD. Rumination patterns in children are similar compared with adults, albeit with lower gastric pressure increase. We propose a diagnostic cutoff for gastric pressure increase >25 mmHg associated with retrograde bolus flow into the proximal esophagus. [ABSTRACT FROM AUTHOR]

SUMMARY Background Reliable data on inflammatory biomarkers for predicting relapse of paediatric inflammatory bowel disease ( IBD) are lacking. Aim To investigate the predictive value of faecal calprotectin (FC) and CRP for symptomatic relapse in pediatric IBD in clinical remission. Methods In this cross-sectional cohort study, patients <18 years with Crohn's disease or ulcerative colitis in clinical remission ≥3 months were included. At baseline, clinical and biochemical disease activity were assessed using the abbreviated-Pediatric Crohn's Disease Activity Index or Pediatric Ulcerative Colitis Activity Index, and FC and CRP respectively. Disease course over the subsequent 12 months was retrospectively assessed. Results In total, 114 patients (56% males; median age 14.9 years) were included. Baseline FC was higher in patients that developed symptomatic relapse [median ( IQR), relapse 370 μg/g (86-1100) vs. remission 122 μg/g (40-344), P = 0.003]. Baseline FC was predictive of symptomatic relapse within 6 months [ HR per 250 μg/g (95% CI): 1.46 (1.21-1.77), P < 0.001], with good predictive accuracy ( AUC: 0.82). Optimal FC cut-off was 350 μg/g, with positive and negative predictive value of 41% and 96%. Baseline CRP was higher in patients that developed symptomatic relapse [median ( IQR), relapse 1.0 μg/g (0.6-5.0) vs. remission 1.0 μg/g (0.4-2.0), P = 0.033]. Baseline CRP was predictive of symptomatic relapse within 6 months from baseline [ HR per 1 mg/L (95% CI): 1.10 (1.02-1.19), P = 0.011], with fair predictive accuracy ( AUC: 0.72). Optimal CRP cut-off was 1.0 mg/L, with positive and negative predictive value of 21% and 94%. Conclusions Faecal calprotectin and CRP are predictive of symptomatic relapse and may be valuable in management of paediatric IBD in clinical remission. [ABSTRACT FROM AUTHOR]

Background There is little published evidence of efficacy for the most commonly used treatments. Thus, there is an urgent need to conduct clinical trials on existing and novel therapies. Purpose In order to address these issues the Rome Foundation and members of the Pediatric Committee of the European Medicines Agency formed a subcommittee on clinical trials to develop guidelines for the design of clinical trials in children with irritable bowel syndrome ( IBS). The following recommendations are based on evidence from published data when available and expert opinion. Key recommendations The subcommittee recommends randomized, double-blind, placebo-controlled, parallel-group, clinical trials to assess the efficacy of new drugs. The combined endpoints for abdominal pain are a decrease in intensity of at least 30% compared with baseline and to meet or exceed the Reliable Change Index ( RCI) for the sample. Stool consistency is measured with the Bristol Stool Scale Form ( BSFS). The subcommittee recommends as entry criteria for abdominal pain a weekly average of worst abdominal pain in past 24 h of at least 3.0 on a 0-10 point scale or at least 30 mm in 100 mm Visual Analog Scale. For stool endpoints the committee recommends an average stool consistency lower than 3 in the BSFS during the run-in period for clinical trials on IBS-C and an average stool consistency greater than 5 in the BSFS during the run-in period for clinical trials on IBS-D. Changes in stool consistency are the primary endpoints for both IBS with diarrhea ( IBS-D) and IBS with constipation ( IBS-C). [ABSTRACT FROM AUTHOR]

Recently, multichannel intraluminal impedance ( MII) monitoring was added to the repertoire of tests to evaluate the (patho)physiology of gastroesophageal reflux ( GER) in children. Its advantage above the sole monitoring of the esophageal pH lies in the ability of the detection of both acid and nonacid GER and to discern between liquid and gas GER. Currently, combined 24 h pH- MII monitoring is recommended for evaluation of gastro-esophageal reflux disease ( GERD) and its relation to symptoms in infants and children, despite the lack of reference values in these age groups. There is new evidence in the current issue of this Journal supporting the role of pH- MII monitoring for the evaluation of children presenting with gastrointestinal symptoms suggestive of GERD and the prediction of the presence of reflux esophagitis. However, several issues should be taken into account when performing pH- MII clinically. [ABSTRACT FROM AUTHOR]

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Defecation-related functional gastrointestinal disorders (FGIDs), such as infant dyschezia, functional constipation and functional non-retentive faecal incontinence, as defined by the Rome IV criteria, are common problems in childhood. The symptomatology varies from relatively mild, such as crying before passage of soft stools or infrequent defecation to severe problems with faecal impaction and the daily involuntary loss of faeces in the underwear. Conventional radiography is widely available, relatively cheap and is non-invasive. The drawback however, is radiation exposure. This review describes and evaluates the value of different existing scoring methods to assess faecal loading on an abdominal radiograph with or without the use of radio-opaque markers, to measure colonic transit time, in the diagnosis of these defecation-related FGIDs. Insufficient evidence exists for a diagnostic association between clinical symptoms of functional constipation or functional nonretentive faecal incontinence and faecal loading on an abdominal radiograph. Furthermore, evidence does not support the routine use of colonic transit studies to diagnose functional constipation. Colonic transit time measurement may be considered in discriminating between functional constipation and functional non-retentive faecal incontinence and in patients in which the diagnosis is not clear such as having an unreliable medical history. In children with the suspicion of defecation-related FGIDs, the diagnosis should be made based on the Rome IV criteria. [ABSTRACT FROM AUTHOR]

Background A large proportion (25-46%) of adults with inflammatory bowel disease in remission has symptoms of irritable bowel syndrome ( IBS), which are thought to reflect ongoing inflammation. Data on paediatric inflammatory bowel disease patients are lacking. Aim To investigate (i) the prevalence of IBS-type symptoms in paediatric inflammatory bowel disease patients in remission and (ii) the relationship of IBS-type symptoms with biochemical markers of disease activity. Methods This cross-sectional study included all patients (<18 years) with Crohn's disease or ulcerative colitis attending the out-patient clinic of one of three Dutch hospitals between March 2014 and June 2015. Clinical disease activity was determined using the abbreviated- PCDAI or PUCAI. Biochemical disease activity was assessed using faecal calprotectin and serum CRP. IBS-symptoms were assessed using physician-administered Rome III-questionnaires. Results We included 184 patients (92 female; mean age: 14.5 years) (Crohn's disease: 123, ulcerative colitis: 61). The prevalence of IBS-type symptoms in children with inflammatory bowel disease in clinical remission was 6.4% (95% CI: 2.5-11.1%; Crohn's disease: 4.5%; ulcerative colitis: 10.8%). Prevalence of IBS-type symptoms in children with faecal calprotectin <250 μg/g was 16.1% (95% CI: 7.6-25.8%; Crohn's disease: 16.7%; ulcerative colitis: 10.8%). No difference in faecal calprotectin or CRP was found between patients in clinical remission with or without IBS-type symptoms (faecal calprotectin: IBS+ median 58 μg/g, IBS− 221 μg/g, P = 0.12; CRP: IBS+ median 1.4 mg/L, IBS− 1.1 mg/L, P = 0.63). Conclusions The prevalence of IBS-type symptoms in children with inflammatory bowel disease is highly dependent on the definition of remission. Nonetheless, the prevalence is much lower than that previously reported in studies in adult inflammatory bowel disease patients. IBS-type symptoms appear to be unrelated to gastrointestinal inflammation. [ABSTRACT FROM AUTHOR]

Background Children with chronic intractable constipation experience severe and long-lasting symptoms, which respond poorly to conventional therapeutic strategies. Detailed characterization of colonic motor patterns in such children has not yet been obtained. Methods In 18 children with chronic intractable constipation, a high-resolution water-perfused manometry catheter (36 sensors at 1.5-cm intervals) was colonoscopically placed with the tip at the distal transverse colon. Colonic motor patterns were recorded for 2 h prior to and after a meal and then after colonic infusion of bisacodyl. These data were compared with previously published colonic manometry data from 12 healthy adult controls and 14 adults with slow-transit constipation. Key Results The postprandial number of the retrograde cyclic propagating motor pattern was significantly reduced in these children compared with healthy adults (children, 3.1 ± 4.7/h vs healthy adults, 34.7 ± 45.8/h; p < 0.0001) but not constipated adults (4.5 ± 5.6/h; p = 0.9). The number of preprandial long-single motor patterns was significantly higher ( p = 0.003) in children (8.0 ± 13.2/h) than in healthy adults (0.4 ± 0.9/h) and in constipated adults (0.4 ± 0.7/h). Postprandial high-amplitude propagating sequences ( HAPSs) were rarely observed in children (2/18), but HAPS could be induced by bisacodyl in 16 of 18 children. Conclusions & Inferences Children with chronic intractable constipation show a similar impaired postprandial colonic response to that seen in adults with slow-transit constipation. Children may have attenuated extrinsic parasympathetic inputs to the colon associated with an increased incidence of spontaneous long-single motor patterns. [ABSTRACT FROM AUTHOR]

Esophageal multiple intraluminal impedance baseline is an additional impedance parameter that was recently related to esophageal integrity. The aim of this study was to assess the relationship between mean esophageal impedance value and endoscopic findings in a large group of children. Children with symptoms of gastroesophageal reflux submitted to both endoscopy and impedance were included. Esophagitis was graded according to the Los Angeles classification. Mean impedance value was automatically calculated over 24-hour tracings. Data were adjusted for age through z-score transformation using percentiles normalized by the LMS (Lambda for the skew, Mu for the median, and Sigma for the generalized coefficient of variation) method. Nonparametric Mann- Whitney and Kruskal- Wallis tests, multiple, and stepwise regression were used. P-value <0.05 was considered as statistically significant. A total of 298 impedance tracings were analyzed. Endoscopic and histological esophagitis were detected in 30 and 29% patients, respectively. Median baseline z-score was significantly decreased both in proximal ( P = 0.02) and distal ( P = 0.01) esophagus in patients with endoscopic (but not histological) esophagitis. Patients with more severe esophagitis showed the lowest z-score. Bolus exposure index and the number of reflux episodes were the variables that were significantly associated with the baseline z-score. Impedance z-score is significantly decreased in infants and children with endoscopic esophagitis. Severity of esophagitis, bolus exposure index, and number of reflux episodes are factors influencing mean esophageal impedance. [ABSTRACT FROM AUTHOR]

Background Anorectal disorders such as dyssynergic defecation, fecal incontinence, levator ani syndrome, and solitary rectal ulcer syndrome are common, and affect both the adult and pediatric populations. Although they are treated with several treatment approaches, over the last two decades, biofeedback therapy using visual and verbal feedback techniques has emerged as an useful option. Because it is safe, it is commonly recommended. However, the clinical efficacy of biofeedback therapy in adults and children is not clearly known, and there is a lack of critical appraisal of the techniques used and the outcomes of biofeedback therapy for these disorders. Purpose The American Neurogastroenterology and Motility Society and the European Society of Neurogastroenterology and Motility convened a task force to examine the indications, study performance characteristics, methodologies used, and the efficacy of biofeedback therapy, and to provide evidence-based recommendations. Based on the strength of evidence, biofeedback therapy is recommended for the short-term and long-term treatment of constipation with dyssynergic defecation (Level I, Grade A), and for the treatment of fecal incontinence (Level II, Grade B). Biofeedback therapy may be useful in the short-term treatment of Levator Ani Syndrome with dyssynergic defecation (Level II, Grade B), and solitary rectal ulcer syndrome with dyssynergic defecation (Level III, Grade C), but the evidence is fair. Evidence does not support the use of biofeedback for the treatment of childhood constipation (Level 1, Grade D). [ABSTRACT FROM AUTHOR]

Background Despite existing criteria for scoring gastro-esophageal reflux ( GER) in esophageal multichannel pH-impedance measurement (pH-I) tracings, inter- and intra-rater variability is large and agreement with automated analysis is poor. To identify parameters of difficult to analyze pH-I patterns and combine these into a statistical model that can identify GER episodes with an international consensus as gold standard. Methods Twenty-one experts from 10 countries were asked to mark GER presence for adult and pediatric pH-I patterns in an online pre-assessment. During a consensus meeting, experts voted on patterns not reaching majority consensus (>70% agreement). Agreement was calculated between raters, between consensus and individual raters, and between consensus and software generated automated analysis. With eight selected parameters, multiple logistic regression analysis was performed to describe an algorithm sensitive and specific for detection of GER. Key Results Majority consensus was reached for 35/79 episodes in the online pre-assessment (interrater κ = 0.332). Mean agreement between pre-assessment scores and final consensus was moderate ( κ = 0.466). Combining eight pH-I parameters did not result in a statistically significant model able to identify presence of GER. Recognizing a pattern as retrograde is the best indicator of GER, with 100% sensitivity and 81% specificity with expert consensus as gold standard. Conclusions & Inferences Agreement between experts scoring difficult impedance patterns for presence or absence of GER is poor. Combining several characteristics into a statistical model did not improve diagnostic accuracy. Only the parameter 'retrograde propagation pattern' is an indicator of GER in difficult pH-I patterns. [ABSTRACT FROM AUTHOR]

It is still unclear how to evaluate the existence of faecal retention or impaction in children with defaecation disorders. To objectivate the presence and degree of constipation we measured segmental and total colonic transit times (CTT) using radio-opaque markers in 211 constipated children. On clinical grounds, patients (median age 8 years (5-14 years)) could be divided into three groups; constipation, isolated encopresis/soiling and recurrent abdominal pain. Barr-scores, a method for assessment of stool retention using plain abdominal radiographs, were obtained in the first 101 patients, for comparison with CTT measurements as to the clinical outcome. Of the children with constipation, 48% showed significantly prolonged total and segmental CTT. Surprisingly, 91% and 91%, respectively, of the encopresis/soiling and recurrent abdominal pain children had a total CTT within normal limits, suggesting that no motility disorder was present. Prolonged CTT through all segments, known as colonic inertia, was found in the constipation group only. Based on significant differences in clinical presentation, CTT and colonic transit patterns, encopresis/soiling children formed a separate entity among children with defaecation disorders, compared to children with constipation. Recurrent abdominal pain in children was in the great majority, not related to constipation. Barr-scores were poorly reproducible, with low inter- and intra-observer reliability. This is the first study which shows that clinical differences in constipated children are associated with different colonic transit patterns. The usefulness of CTT measurements lies in the objectivation of complaints and the discrimination of certain transit patterns. Conclusion. Abdominal radiographs, even when assessed with the Barr-score proved unreliable in diagnosing constipation.(ABSTRACT TRUNCATED AT 250 WORDS) [ABSTRACT FROM AUTHOR]

Background The Chicago Classification ( CC) facilitates interpretation of high-resolution manometry ( HRM) recordings. Application of this adult based algorithm to the pediatric population is unknown. We therefore assessed intra and interrater reliability of software-based CC diagnosis in a pediatric cohort. Methods Thirty pediatric solid state HRM recordings (13M; mean age 12.1 ± 5.1 years) assessing 10 liquid swallows per patient were analyzed twice by 11 raters (six experts, five non-experts). Software-placed anatomical landmarks required manual adjustment or removal. Integrated relaxation pressure ( IRP4s), distal contractile integral ( DCI), contractile front velocity ( CFV), distal latency ( DL) and break size ( BS), and an overall CC diagnosis were software-generated. In addition, raters provided their subjective CC diagnosis. Reliability was calculated with Cohen's and Fleiss' kappa ( κ) and intraclass correlation coefficient ( ICC). Key Results Intra- and interrater reliability of software-generated CC diagnosis after manual adjustment of landmarks was substantial (mean κ = 0.69 and 0.77 respectively) and moderate-substantial for subjective CC diagnosis (mean κ = 0.70 and 0.58 respectively). Reliability of both software-generated and subjective diagnosis of normal motility was high ( κ = 0.81 and κ = 0.79). Intra- and interrater reliability were excellent for IRP4s, DCI, and BS. Experts had higher interrater reliability than non-experts for DL ( ICC = 0.65 vs ICC = 0.36 respectively) and the software-generated diagnosis diffuse esophageal spasm ( DES, κ = 0.64 vs κ = 0.30). Among experts, the reliability for the subjective diagnosis of achalasia and esophageal gastric junction outflow obstruction was moderate-substantial ( κ = 0.45-0.82). Conclusions & Inferences Inter- and intrarater reliability of software-based CC diagnosis of pediatric HRM recordings was high overall. However, experience was a factor influencing the diagnosis of some motility disorders, particularly DES and achalasia. [ABSTRACT FROM AUTHOR]

What is already known about this subject Visceral fat accumulation is a risk factor for obesity-related complications., Waist circumference is used in clinical practice to assess visceral adiposity., What this study adds Ultrasound is not superior to waist circumference for assessing visceral obesity in obese children., The optimal site for measuring waist circumference in obese children is at the smallest body circumference between xiphisternum and umbilicus., Objective Visceral fat accumulation is a well-established risk factor for obesity-related complications. In children, it has not been determined whether ultrasonography is superior to waist measurement for assessing visceral fat. Moreover, the optimal site for waist measurement has not been determined. Design In a prospective cohort of 92 severely obese children and adolescents (age 13.9 ± 2.2 years, body mass index z-score 3.29 ± 0.33), we evaluated the performance of ultrasonography and two different methods of waist circumference measurement, using magnetic resonance imaging as the reference standard. Results Waist circumference, defined as the smallest body circumference between xiphisternum and umbilicus had the strongest correlation with visceral fat quantity ( r = 0.69 all, r = 0.68 girls, r = 0.64 boys). It was not outperformed by ultrasonography ( r = 0.60 all, r = 0.62 girls, r = 0.50 boys) and correlated significantly better than the World Health Organization standard for waist measurement, midway between lower margin of the last rib and the crest of the ilium, ( r = 0.51 all, r = 0.39 girls, r = 0.46 boys). Conclusions Waist circumference measurement, defined as the smallest body circumference between xiphisternum and umbilicus, is the preferred non-invasive technique for daily clinical practice to assess visceral fat accumulation in severely obese children and adolescents. There is no place for ultrasonography for the quantification of visceral fat in this group. [ABSTRACT FROM AUTHOR]

Background Applying the 2012 Chicago Classification ( CC) of esophageal motility disorders to pediatric patients is problematic as it relies upon adult-derived criteria. As shorter esophageal length and smaller esophago-gastric junction ( EGJ) diameter may influence CC metrics, we explored the potential for age- and size-adjustment of diagnostic criteria. Methods We evaluated 76 high-resolution solid state impedance-manometry recordings in children referred for manometry (32M; mean age 9 ± 1 years) and 25 recordings from healthy adult subjects (7M; mean age 36 ± 2 years). CC metrics; integrated relaxation pressure ( IRP4s, mmHg), contractile front velocity ( CFV, cm/s), distal contractile integral ( DCI, mmHg cm/s), distal latency ( DL, s), and peristaltic break size ( BS, cm) were derived for 10 liquid swallows using CC analysis software. Effects of age and size were examined using regression analysis. Key Results Younger patient age and shorter size correlated significantly with greater IRP4s ( p < 0.05), shorter DL ( p < 0.001) and smaller BS ( p < 0.05). Standard diagnostic CC criteria were adjusted using the slope of the linear regression equation to define the age/size-related trend. Sixty-six percent of the pediatric cohort showed abnormal motility when applying standard CC criteria. Adjustment for age and size reduced this to 50% and 53% respectively, with the largest reduction being in the IRP4s- and DL-dependent disorders EGJ outflow obstruction and diffuse esophageal spasm (13% to 7% and 5% and 14% to 1 and 5%, respectively). Conclusions & Inferences CC metrics, particularly IRP4s and DL, are age and size dependent, and therefore, require adjustment to improve accuracy of diagnosis of esophageal motility disorders in children. [ABSTRACT FROM AUTHOR]

Introduction:Cholelithiasis is increasingly encountered in childhood and adolescence due to the rise in obesity. As in adults, weight loss is presumed to be an important risk factor for cholelithiasis in children, but this has not been studied.Methods:In a prospective observational cohort study we evaluated the presence of gallstones in 288 severely obese children and adolescents (mean age 14.1±2.4 years, body mass index (BMI) z-score 3.39±0.37) before and after participating in a 6-month lifestyle intervention program.Results:During the lifestyle intervention, 17/288 children (5.9%) developed gallstones. Gallstones were only observed in those losing >10% of initial body weight and the prevalence was highest in those losing >25% of weight. In multivariate analysis change in BMI z-score (odds ratio (OR) 3.26 (per 0.5 s.d. decrease); 95% CI:1.60-6.65) and baseline BMI z-score (OR 2.32 (per 0.5 s.d.); 95% CI: 1.16-4.70) were independently correlated with the development of gallstones. Sex, family history, OAC use, puberty and biochemistry were not predictive in this cohort. During post-treatment follow-up (range 0.4-7.8 years) cholecystectomy was performed in 22% of those with cholelithiasis. No serious complications due to gallstones occurred.Conclusion:The risk of developing gallstones in obese children and adolescents during a lifestyle intervention is limited and mainly related to the degree of weight loss and initial body weight. [ABSTRACT FROM AUTHOR]

In children with gastroesophageal reflux (GER) disease refractory to pharmacological therapies, anti-reflux surgery (fundoplication) may be a treatment of last resort. The applicability of fundoplication has been hampered by the inability to predict which patient may benefit from surgery and which patient is likely to develop post-operative dysphagia. pH impedance measurement and conventional manometry are unable to predict dysphagia, while the role of gastric emptying remains poorly understood. Recent data suggest that the selection of patients who will benefit from surgery might be enhanced by automated impedance manometry pressure-flow analysis (AIM) analysis, which relates bolus movement and pressure generation within the esophageal lumen. [ABSTRACT FROM AUTHOR]

Background Posture has been shown to influence the number of transient lower esophageal sphincter relaxation (TLESRs) and gastroesophageal reflux (GER), however, the physiology explaining the influence of right lateral position (RLP), and left lateral position (LLP) is not clear. The aim of this study was to determine the influence of RLP and LLP on TLESRs and GERD after a meal in GER disease (GERD) patients and healthy controls (HC) while monitoring gastric distension and emptying. Methods Ten GERD patients and 10 HC were studied for 90 min (30 min test meal infusion, 30 min postprandial in either RLP or LLP (randomly assigned) and 30 min in alternate position). The study was repeated on a separate day in reverse position order. TLESRs, GER, and gastric emptying rate were recorded using manometry, multichannel intraluminal impedance, and 13C-octanoate breath tests. Gastric distension was visualized by five serial gastric volume scintigraphy scans during the first 30 min. Key Results Gastroesophageal reflux, (GER) disease patients had increased numbers of TLESRs in RLP compared to LLP in the first postprandial hour [5 (4-14) and 4.5 (2-6), respectively, P = 0.046] whereas the number of TLESRs was not different in RLP and LLP [4 (2-4) and 4 (3-6), respectively, P = 0.7] in HC. Numbers of GER increased similar to TLESRs in GERD patients. In GERD patients, gastric emptying reached peak 13CO2 excretion faster and proximal gastric distension was more pronounced. Conclusions & Inferences In GERD patients, TLESRs, GER, distension of proximal stomach, and gastric emptying are increased in RLP compared to LLP. This effect is not seen in HC. [ABSTRACT FROM AUTHOR]

Background Faecal incontinence ( FI) in children is a significant gastrointestinal problem, with great personal and social impacts. It is characterised by recurrent loss of faecal matter into the underwear. Both functional and organic causes contribute to its aetiology with the former predominating. Aim To review the epidemiology, pathophysiology, clinical evaluation and management of functional faecal incontinence in children. Methods A PubMed search was conducted using search terms f(a)ecal incontinence, and encopresis. Articles on epidemiology, pathophysiology, clinical evaluation, investigation and management of functional FI in children were retrieved and assessed. Results Community prevalence of this distressing problem ranges from 0.8% to 7.8% globally. Male: female ratio varies from 3:1 to 6:1. The diagnosis of FI is often based on established clinical criteria. The majority (82%) have constipation associated functional FI. Biopsychosocial factors play a crucial role in the pathogenesis. Limited physiological testing of anorectal function is recommended in the diagnostic procedures, particularly in children with atypical symptoms and possible organic disorders. Management of FI needs a multidisciplinary approach which includes establishment of an effective doctor-patient partnership, understanding the underlying mechanisms, pharmacotherapy and behavioural treatment. Approximately 15% of children with functional nonretentive faecal incontinence ( FNRFI) had the same symptoms at the age of 18 years. Conclusion Significant therapeutic advances have been made for retentive faecal incontinence, but treatment options for functional nonretentive faecal incontinence are limited. Limited long-term outcome data show that the majority outgrow faecal incontinence. A substantial proportion of children progress to adulthood with faecal incontinence. [ABSTRACT FROM AUTHOR]