Bowel Lengthening Procedures in Children with Short Bowel Syndrome: A Systematic Review.

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.

Reporting on outcome measures in pediatric chronic intestinal failure: A systematic review.

BACKGROUND & AIMS: Chronic intestinal failure (IF) in children is a rare and heterogeneous disease requiring treatment with parenteral nutrition. A uniform definition for chronic IF and standardized outcome measures to compare therapeutic trials in these children are lacking. Therefore, the aim of this study is to systematically assess how definitions and outcome measures are defined in therapeutic trials of children with chronic IF. METHODS: MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched from inception till August 2018. No language restriction was used. RESULTS: A total of 1766 articles was found of which 70 studies fulfilled our inclusion criteria. 54 studies (76%) did not report any definition of IF. Of the 16 studies (23%) which reported a definition of IF, 7 different definitions were found. The two most frequently used definitions were: (1) the inability to absorb adequate nutrients to maintain body weight or normal growth and development (n = 5), and (2) the dependence upon parenteral nutrition to maintain minimal energy requirements for growth and development (n = 5). A total of 117 different outcomes were reported. The three most reported outcome measures were: mortality (n = 27), liver enzymes (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and gamma-glutamyl trans peptidase) (n = 27), and growth (n = 23). Quality of reporting was considered fair to poor in most studies. CONCLUSION: There is a lack of reported definitions in studies concerning pediatric IF. Heterogeneity exists in outcome reporting in research concerning pediatric chronic IF. Therefore, we recommend the development of a core outcome set.

[Guideline on functional abdominal pain in children]. / Richtlijn 'Functionele buikpijn bij kinderen'.

- The guideline entitled 'Functional abdominal pain in children' has been developed by a multidisciplinary working group on behalf of the Dutch Pediatric Association in 2015. - History and physical examination are essential in diagnosing pediatric functional abdominal pain. Additional diagnostic testing is of limited value when alarm symptoms are absent. - Reassurance and education of both the child and parent(s), are the cornerstones in the treatment of pediatric functional abdominal pain. - In case of persisting symptoms, hypnotherapy or cognitive behavioral therapy can be started. There is no evidence for any pharmacological treatment.

Outcome after restorative proctocolectomy and ileal pouch-anal anastomosis in children and adults.

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.

[Functional abdominal symptoms in children: the role of the abdominal X-ray and measurement of colon transit time]. / Functionele buikklachten bij kinderen.

Functional constipation and functional non-retentive faecal incontinence are common problems in childhood; these functional defaecation disorders are diagnosed according to the Rome IV criteria. Here we describe the role of an abdominal X-ray in diagnosing functional defaecation disorders, and address the limited additional value of a plain abdominal X-ray. In limited cases it may be helpful to determine colonic transit time using an abdominal X-ray to differentiate between functional constipation and functional non-retentive faecal incontinence. The diagnostic value of abdominal X-rays in children with functional abdominal pain will be discussed. The aims of this article are to explore ways of reducing unnecessary use of abdominal X-rays and reducing unnecessary radiation exposure in children with functional defaecation disorders and functional abdominal pain.

Raised faecal calprotectin is associated with subsequent symptomatic relapse, in children and adolescents with inflammatory bowel disease in clinical remission.

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.

How to use a plain abdominal radiograph in children with functional defecation disorders.

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.

The prevalence of irritable bowel syndrome-type symptoms in paediatric inflammatory bowel disease, and the relationship with biochemical markers of disease activity.

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.

Presentation of a nationwide multicenter registry of intestinal failure and intestinal transplantation.

BACKGROUND & AIMS: Exact data on Dutch patients with chronic intestinal failure (CIF) and after intestinal transplantation (ITx) have been lacking. To improve standard care of these patients, a nationwide collaboration has been established. Objectives of this study were obtaining an up-to-date prevalence of CIF and characterizing these patients using the specially developed multicenter web-based Dutch Registry of Intestinal Failure and Intestinal Transplantation (DRIFT). METHODS: Cross-sectional study. CIF was defined as type 3 intestinal failure in which >75% of nutritional requirements were given as home parenteral nutrition (HPN) for ≥ 4 weeks in children and >50% for ≥3 months in adults. All patients with CIF receiving HPN care by the three Dutch specialized centers on January 1, 2013 and all ITx patients were registered in DRIFT (https://drift.darmfalen.nl). RESULTS: In total, 195 patients with CIF (158 adults, 37 children) were identified, of whom 184 were registered in DRIFT. The Dutch point prevalence of CIF was 11.62 per million (12.24 for adults, 9.56 for children) on January 1, 2013. Fifty-seven patients (31%) had one or more indications for ITx, while 12 patients actually underwent ITx since its Dutch introduction. Four patients required transplantectomy of their intestinal graft and 3 intestinal transplant patients died. CONCLUSION: The multicenter registry DRIFT revealed an up-to-date prevalence of CIF and provided nationwide insight into the patients with CIF during HPN and after ITx in the Netherlands. DRIFT will facilitate the multicenter monitoring of individual patients, thereby supporting multidisciplinary care and decision-making.

False negative newborn screen and neonatal cholestasis in a premature child with cystic fibrosis.

UNLABELLED: Newborn screening for cystic fibrosis enables early diagnosis and treatment, leading to better outcomes for patients with cystic fibrosis. Although the sensitivity of several screening protocols is high, false negative screening results of the newborn patient still occur, which can lead to a significant delay in diagnosis when the awareness for presenting symptoms of cystic fibrosis declines. Neonatal cholestasis is one of the presenting symptoms of cystic fibrosis but can be easily missed when total parenteral nutrition has been given. Premature newborns are probably more at risk of a missed underlying diagnosis than term babies because their co-pathologies and management are often more complex. We present a case of a 10-week-old premature boy with a false negative newborn screening for cystic fibrosis, in whom cystic fibrosis presented with neonatal cholestasis. In this case, the immunoreactive trypsinogen/pancreatitis-associated protein/35 cystic fibrosis transmembrane regulator mutation analysis/sequencing method was used. Furthermore, an overview of the literature on missed diagnosis of cystic fibrosis due to a false negative newborn screen is provided. CONCLUSION: Cystic fibrosis (CF) should be considered in infants with neonatal cholestasis even when the newborn screening for CF is reported to be negative.

Evaluation and treatment of functional constipation in infants and children: evidence-based recommendations from ESPGHAN and NASPGHAN.

BACKGROUND: Constipation is a pediatric problem commonly encountered by many health care workers in primary, secondary, and tertiary care. To assist medical care providers in the evaluation and management of children with functional constipation, the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition were charged with the task of developing a uniform document of evidence-based guidelines. METHODS: Nine clinical questions addressing diagnostic, therapeutic, and prognostic topics were formulated. A systematic literature search was performed from inception to October 2011 using Embase, MEDLINE, the Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Clinical Trials, and PsychInfo databases. The approach of the Grading of Recommendations Assessment, Development and Evaluation was applied to evaluate outcomes. For therapeutic questions, quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation system. Grading the quality of evidence for the other questions was performed according to the classification system of the Oxford Centre for Evidence-Based Medicine. During 3 consensus meetings, all recommendations were discussed and finalized. The group members voted on each recommendation, using the nominal voting technique. Expert opinion was used where no randomized controlled trials were available to support the recommendation. RESULTS: This evidence-based guideline provides recommendations for the evaluation and treatment of children with functional constipation to standardize and improve their quality of care. In addition, 2 algorithms were developed, one for the infants <6 months of age and the other for older infants and children. CONCLUSIONS: This document is intended to be used in daily practice and as a basis for further clinical research. Large well-designed clinical trials are necessary with regard to diagnostic evaluation and treatment.

Small bowel endoscopy in children.

Endoscopic investigation of small bowel pathology in children has historically been difficult due to location, length and tortuosity of the small bowel. Recently, video capsule endoscopy and balloon-assisted enteroscopy techniques have evolved as new diagnostic tools and are increasingly used in the paediatric population. In this review the current literature is appraised to define the clinical indications and practical aspects of capsule endoscopy and balloon-assisted enteroscopy in children.

Prophylactic anticoagulation decreases catheter-related thrombosis and occlusion in children with home parenteral nutrition.

BACKGROUND: Home parenteral nutrition (PN) has improved the survival of children with intestinal failure. Important complications include catheter-related thrombosis, occlusion, and infection. This study evaluated the efficacy and safety of prophylactic anticoagulation in the prevention of these complications. METHODS: Medical records were retrospectively reviewed of all children (0-18 years) with PN between January 1994 and March 2007 in 1 tertiary center. After introduction of prophylactic low molecular weight heparin or vitamin K antagonists in March 2007, all patients were prospectively followed until March 2010. RESULTS: In sum, 14 patients did not receive prophylaxis; 13 switched from no prophylaxis to prophylaxis in March 2007; and 5 directly received prophylaxis. Median age of PN onset was 4 months (range, 0.1-202) in the nonprophylaxis group (n = 27) and 25 (range, 2-167) in the prophylaxis group (n = 18); 16 children received low molecular weight heparin and 2, vitamin K antagonists. Catheter-related thrombosis developed in 9 patients with no prophylaxis (33%) and 1 with prophylaxis (6%) (P = .034). Cumulative 5-year thrombosis-free survival was 48% and 93% in the nonprophylaxis and prophylaxis groups, respectively (P = .047). Per 1,000 PN days, the nonprophylaxis and prophylaxis groups had 2.6 and 0.1 occlusions (P = .04) and 4.6 and 2.1 infections (P = .06), respectively. Cumulative infection-free survival after 3 years was 19% and 46% in the nonprophylaxis and prophylaxis groups, respectively (P = .03). Bleeding complications did not occur. CONCLUSION: Thromboprophylaxis significantly decreased catheter-related thrombosis and occlusion in children with PN without complications.

Is Bifidobacterium breve effective in the treatment of childhood constipation? Results from a pilot study.

BACKGROUND: Probiotics are increasingly used in the treatment of functional gastrointestinal disorders. Studies in constipated adults with a Bifidus yoghurt (containing Bifidobacterium breve, Bifidobacterium bifidum and Lactobacillus acidophilus) showed a significant increase in defecation frequency. The aim of this pilot study was to determine if Bifidobacterium breve is effective in the treatment of childhood constipation. METHODS: Children, 3 to 16 years of age, with functional constipation according to the Rome III criteria were eligible for this study. During 4 weeks, children received one sachet of powder daily, containing 108- 1010 CFU Bifidobacterium breve. Furthermore, children were instructed to try to defecate on the toilet for 5-10 minutes after each meal and to complete a standardized bowel diary daily. The primary outcome measure was change in defecation frequency. Secondary outcome measures were stool consistency using the Bristol stool scale frequency of episodes of faecal incontinence, pain during defecation, frequency of abdominal pain, frequency of adverse effects (nausea, diarrhoea and bad taste), and frequency of intake of bisacodyl. RESULTS: Twenty children (75% male, mean age 7.4) were included in this pilot study. The defecation frequency per week significantly increased from 0.9 (0-2) at baseline to 4.9 (0-21) in week 4 (p < 0.01). The mean stool consistency score increased from 2.6 (2-4) at baseline to 3.5 (1-6) in week 4 (p = 0.03). The number of faecal incontinence episodes per week significantly decreased from 9.0 (0-35) at baseline to 1.5 (0-7) in week 4 (p < 0.01). Abdominal pain episodes per week significantly decreased from 4.2 (0-7) at baseline to 1.9 (0-7) in week 4 (p = 0.01). No side effects occurred. CONCLUSION: Bifidobacterium breve is effective in increasing stool frequency in children with functional constipation. Furthermore it has a positive effect with respect to stool consistency, decreasing the number of faecal incontinence episodes and in diminishing abdominal pain. A randomized placebo controlled trial is required to confirm these data.

Is endoscopic retrograde cholangiopancreatography valuable and safe in children of all ages?

OBJECTIVE: To evaluate indications, findings, therapies, safety, and technical success of endoscopic retrograde cholangiopancreatography (ERCP) in children of the Emma Children's Hospital Academic Medical Centre in Amsterdam, the Netherlands. DESIGN: Descriptive. Retrospective analysis by medical records. PATIENTS AND METHODS: Information was obtained by chart review of patients between 0 and 18 years who underwent ERCP from 1995 to 2005 in our center. The following data were analyzed: indications, findings, therapies, safety, and technical success. Success was defined as obtaining accurate diagnostic information or succeeding in endoscopic therapy. RESULTS: Sixty-one children (age 3 days to 16.9 years, mean age 7.0 years) underwent a total of 99 ERCPs. Of those patients, 51% (31/61) were younger than 1 year, 84% had biliary indications, and 16% had pancreatic indications for the performance of ERCP. The complication rate was 4% (4/99) and included substantial pancreatitis and mild irritated pancreas. No complications occurred in children younger than 1 year. CONCLUSIONS: ERCP is a safe and valuable procedure for children of all ages with suspicion of pancreaticobiliary diseases. Indications for ERCP are different for children and adults. A laparotomy could be prevented in 12% of children with suspicion of biliary atresia. Further research is required to determine the role of MRCP versus ERCP.

Currently recommended treatments of childhood constipation are not evidence based: a systematic literature review on the effect of laxative treatment and dietary measures.

INTRODUCTION: Constipation is a common complaint in children and early intervention with oral laxatives may improve complete resolution of functional constipation. However, most treatment guidelines are based on reviews of the literature that do not incorporate a quality assessment of the studies. OBJECTIVE: To investigate and summarise the quantity and quality of the current evidence for the effect of laxatives and dietary measures on functional childhood constipation. METHODS: The Medline and Embase databases were searched to identify studies evaluating the effect of a medicamentous treatment or dietary intervention on functional constipation. Methodological quality was assessed using a validated list of criteria. Data were statistically pooled, and in case of clinical heterogeneity results were summarised according to a best evidence synthesis. RESULTS: Of the 736 studies found, 28 met the inclusion criteria. In total 10 studies were of high quality. The included studies were clinically and statistically heterogeneous in design. Most laxatives were not compared to placebo. Compared to all other laxatives, polyethylene glycol (PEG) achieved more treatment success (pooled relative risk (RR): 1.47; 95% CI 1.23 to 1.76). Lactulose was less than or equally effective in increasing the defecation frequency compared to all other laxatives investigated. There was no difference in effect on defecation frequency between fibre and placebo (weighted standardised mean difference 0.35 bowel movements per week in favour of fibre, 95% CI -0.04 to 0.74). CONCLUSION: Insufficient evidence exists supporting that laxative treatment is better than placebo in children with constipation. Compared to all other laxatives, PEG achieved more treatment success, but results on defecation frequency were conflicting. Based on the results of this review, we can give no recommendations to support one laxative over the other for childhood constipation.

[Administration of probiotic lactobacilli to children with gastrointestinal problems: there is still little evidence]. / Toepassing van probiotische lactobacillen bij kinderen met gastro-intestinale klachten: nog weinig evidence.

Probiotics are defined as 'live micro-organisms that confer a health benefit on the host if administered in adequate amounts'. There are only limited data in the literature regarding the efficacy and safety of lactobacilli for various gastrointestinal indications in children. Lactobacillus rhamnosus GG (LGG) has no added value in the treatment of children with functional constipation. Lactobacilli do seem to be effective in rotavirus diarrhoea. They seem safe and shorten the duration of the diarrhoea by about 1 day. For the prevention of infectious diarrhoea, lactobacilli are only moderately effective and the clinical relevance is unclear. There is 1 controlled study in which LGG had a preventive effect on the development of atopic eczema (but not of allergy to cow's milk) in newborn infants.

[Video-capsule endoscopy in children with unexplained symptoms of the small intestine]. / Videocapsule-endoscopie bij kinderen met onbegrepen aandoeningen van de dunne darm.

Video-capsule endoscopy was used in 4 children with unexplained symptoms of the small intestine. Each patient swallowed a capsule of 11 by 27 mm, which contained a camera that takes 2 images per second (in children aged less than 8 years, the capsule was placed in the duodenum under sedation). In a 3-year-old girl with rectal bleeding following partial resection of the colon and small intestine, ulcers were seen proximal to the ileorectal anastomosis. In a 14-year-old boy with Crohn's disease and an abnormal growth curve, multiple stenoses of the small intestine were seen. In an 8-year-old boy with rectal bleeding, a solitary polypoid mass was seen that, upon operation, appeared to be the result of a partially invaginated Meckel's diverticulum. In a 17-year-old boy with weight loss, rectal bleeding and colitis, abnormalities were seen that were consistent with Crohn's disease. Patients were treated based on the endoscopic results and subsequently recovered. Video-capsule endoscopy is non-invasive and painless and provides better images of the small intestine than a standard endoscopic and radiological examination.