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Constipation is a common problem in children, accounting for about 3% of all primary care visits and up to 25% of referrals to paediatric gastroenterologists. Although polyethylene glycol often proves effective, most children require prolonged treatment and about 50% of them have at least one relapse within the first 5 years after initial recovery. When conventional treatment fails, children are considered to have refractory constipation. Children with refractory constipation deserve specialist management and guidance. Over the last decades, there has been a remarkable increase in our knowledge of normal and abnormal colonic and anorectal motility in children, and a number of different techniques to measure transit and motility have been developed. The present review analyses the possible diagnostic investigations for children with refractory constipation, focusing on their actual indications and their utility in clinical practice. Moreover, we have also analytically reviewed medical and surgical therapeutic options, which should be considered in selected patients in order to achieve the best clinical outcome., Competing Interests: Conflict of interest The authors Paolo Quitadamo, Renato Tambucci, Valentina Mancini, Angelo Campanozzi, Tamara Caldaro, Valentina Giorgio, Licia Pensabene, Sara Isoldi, Saverio Mallardo, Fabio Fusaro, Annamaria Staiano, Silvia Salvatore and Osvaldo Borrelli have no conflicts of interest to declare related to the manuscript., (Copyright © 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Colonic manometry with intraluminal bisacodyl infusion can be used to assess colonic neuromuscular function in children with treatment-refractory constipation. If bisacodyl does not induce high-amplitude propagating contractions (HAPCs), this can be an indication for surgical intervention. A detailed characterization of the colonic response to intraluminal bisacodyl in children with constipation may help to inform clinical interpretation of colonic manometry studies., Methods: Studies were performed in five pediatric hospitals. Analysis included identification of HAPCs, reporting HAPCs characteristics, and an area under the curve (AUC) analysis. Comparisons were performed between hospitals, catheter type, placement techniques, and site of bisacodyl infusion., Results: One hundred and sixty-five children were included (median age 10, range 1-17 years; n = 96 girls). One thousand eight hundred and ninety-three HAPCs were identified in 154 children (12.3 ± 8.8 HAPCs per child, 0.32 ± 0.21 HAPCs per min; amplitude 113.6 ± 31.5 mm Hg; velocity 8.6 ± 3.8 mm/s, propagation length 368 ± 175 mm). The mean time to first HAPC following bisacodyl was 553 ± 669 s. Prior to the first HAPC, there was no change in AUC when comparing pre- vs post-bisacodyl (Z = -0.53, P = .60). The majority of HAPCs terminated in a synchronous pressurization in the rectosigmoid. Defecation was associated with HAPCs (χ 2 (1)=7.04, P < .01). Site of bisacodyl administration, catheter type, and hospital location did not alter the response., Conclusions and Inferences: Intraluminal bisacodyl induced HAPCs in 93% of children with treatment-refractory constipation. The bisacodyl response is characterized by ≥1 HAPC within 12 minutes of infusion. The majority of HAPCs terminate in a synchronous pressurization in the rectosigmoid. Optimal clinical management based upon colonic manometry findings is yet to be determined., (© 2020 John Wiley & Sons Ltd.)

Defecatory disorders in children, including chronic constipation (CC) and fecal incontinence (FI), are common conditions worldwide and have a significant impact on children, their families, and the healthcare system. Anorectal manometry (ARM) and high-resolution anorectal manometry (HRAM) are relatively novel tools for the assessment of anal sphincter function and rectal sensation and have contributed significantly to improving the understanding of the anorectum as a functional unit. ARM has been recognized as the investigation of choice for adults with symptoms of defecation disorders, including fecal incontinence (FI), evacuation difficulties, and constipation. Although it is the gold standard tool in adults, it has yet to be formally accepted as a standardized diagnostic tool in the pediatric age, with limited knowledge regarding indications, protocol, and normal values. ARM/HRAM is slowly becoming recognized among pediatricians, but given that there are currently no agreed guidelines there is a risk that will lead to diversity in practice. The British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN)-Motility Working Group (MWG) therefore has taken the opportunity to provide guidance on the use of ARM/HRAM in children with CC and/or FI., (© 2020 John Wiley & Sons Ltd.)

Background: 'Intractable constipation' (IC) is constipation unresponsive to 3 months of optimal conventional treatment. Colonic manometry (CM) is recommended as a diagnostic modality for evaluation of these children. This study aimed to review outcomes of children with IC who were managed surgically at a single tertiary care center., Methods: Records of children with IC who were treated with ACE (antegrade colonic enema), colostomy, or ileostomy (2006-2018) were reviewed. "Success" was defined as adequate evacuation without need for further unplanned surgery. Data are median (range)., Results: Sixty-seven children underwent surgery, of whom 56 with preoperative CM were included. Age at surgery was 8.6 (3.3-15.1) years. Eight had normal manometry and underwent ACE with 75% success. Thirty-six had left-sided dysfunction and underwent ACE (18), colostomy (14) or ileostomy (4) as initial intervention with 61, 70, and 100% success. Twelve with pancolonic dysfunction underwent ACE (6) or ileostomy (6) with 60 and 100% success. Twenty underwent repeat manometry 2.2 years (10 months-7.6 years) after surgery. Of 18 with stoma, 8 had resolution or improvement and of these, 7 underwent stoma reversal with a simultaneous ACE. Two patients with ACE had improvement, 1 is still on ACE washouts, and 1 is off all treatment. Ten with persistent dysfunction remain diverted. At 3.2 years (4 months-9.9 years) follow-up, 18 remain on ACE washouts, 9 have colostomy, 19 ileostomy, and 10 are off treatment and doing well., Conclusion: We present a large series of patients who were surgically managed for IC. CM may guide therapy in these children., Type of Study: Retrospective comparative study LEVEL OF EVIDENCE: Level III., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Constipation is one of the most common gastrointestinal symptoms in children. With a median reported prevalence of 12%, it accounts for about 25% of all pediatric gastroenterology consultations. The majority of children experiences functional constipation and do not usually require any diagnostic testing. For those children not responding to conventional medical treatment or in the presence of a more significant clinical picture, however, an accurate instrumental assessment is usually recommended to evaluate either the underlying pathophysiologic mechanisms or a possible organic etiology. The present review analyzes the possible diagnostic investigations for severely constipated children, focusing on their actual indications and their utility in clinical practice. During the last decade, there has been a remarkable increase in our knowledge of normal and abnormal colonic and anorectal motility in children, and a number of different techniques to measure transit and motility have been developed and are discussed in this narrative review.

Purpose: To report outcomes of children with constipation refractory to medical management and manometrically proven distal colonic dysmotility, managed with rectosigmoidectomy followed by Duhamel operation (Duhamel)., Methods: Children who underwent a Duhamel from 2009 onwards for intractable constipation and left colonic dysmotility were retrospectively reviewed. The primary end point was resolution of constipation, and secondary end point was postoperative complications. Continuous data were median (range)., Results: 11 patients (4 males) had Duhamel at 11 years (5-16) with constipation started from 2 years (1-8). Hirschsprung's disease was excluded. All Duhamels were performed with a covering ileostomy: 9 following a Hartmann procedure, one following a previously failed reversal of Hartmann, and one Duhamel performed with a pre-existing ileostomy. All ileostomies were subsequently closed. Median resection length was 22 cm (11-31). Length of stay was 8 days (5-23). Follow-up was 5 years (0.5-7). Age at final review was 15 years (10-18). Resolution of constipation occurred in nine patients (4 required antegrade continence enemas (ACE), 5 with laxative); two had persistent constipation and faecal incontinence despite ACE, ultimately requiring an ileostomy. Two postoperative small bowel obstructions required laparotomy., Conclusion: Duhamel performed in children with manometrically proven distal colonic dysmotility yielded 82% resolution of refractory constipation; half of them subsequently needed ACE.

We evaluated the effect of bowel preparation on colonic transit time (CTT) measured by the radio-opaque marker test in children with constipation. All children underwent 2 radio-opaque marker-CTT tests, both in cleansed and uncleansed bowel state. Our findings confirm that the state of colonic fecal filling may significantly influence CTT., (Copyright © 2015. Published by Elsevier Inc.)

Objective: This multicenter prospective study aimed to establish possible risk factors for functional constipation (FC) in the first year of life., Methods: At the infant's age of 3, 6, and 12 months, parents of all included infants completed 2 questionnaires: one about the presence of FC and the other screened the possible risk factors for FC. Parents of 465 infants completed the questionnaires at 3 and 6 months and of 402 infants at 12 months of life., Results: According to the Rome III criteria, FC was found in 11.6% of the infants at 3 months, in 13.7% at 6 months, and in 10.7% at 12 months after birth. Family history of atopy was present in 38.8% and 45.3% of infants with constipation at 3 and 6 months (P = 0.04 and P = 0.02, respectively), but no significant association was found at 12 months (P = 0.80). Breast-feeding was significantly related to a normal evacuation pattern at 3 months (P = 0.05), but not at 6 and 12 months (P = 0.12 and P = 0.9, respectively). Acetaminophen and female sex appeared to be risk factors for FC at 12 months. After the adjustment for all analyzed variables, FC in infants was significantly associated with the use of acetaminophen (odds ratio 6.98, 95% confidence interval 0.82-13.50)., Conclusions: Our results confirmed that breast-feeding is a protective factor for FC in the first 3 months of life and that the female sex is at risk to have FC. We found that the use of acetaminophen was associated with a higher incidence of FC in the first year of life.

Objectives: Food allergy is thought to trigger functional constipation in children but the underlying mechanisms are still unknown. Mast cells (MCs) and their relationship with nerve fibers (NFs) in the rectal mucosa, as well as anorectal motility, were studied in children with refractory chronic constipation before and after an elimination diet for cow's milk, egg, and soy proteins., Methods: Thirty-three children (range: 1-10.8 years) underwent anorectal manometry and suction rectal biopsy before and after 8 weeks of oligoantigenic diet. MCs and NFs were identified immunohistochemically. Quantification of MCs (%MC/area) and MCs within 10 microm of NFs (%MC-NF/area) was performed by computer-assisted analysis., Results: Eighteen children responded to the diet (R-group) and fifteen did not (the NR-group). At baseline there was a significant difference in anal resting pressure (ARP; mm Hg), percentage of relaxation (%R), and residual pressure (RP; mm Hg) of anal canal during rectal distension between the R-group (66+/-4.1, 84.3+/-2.8, 10.4+/-2.3, respectively) and the NR-group (49+/-5, 92.2+/-1.7, 4.8+/-1.7, respectively; P<0.05). After the diet, significant changes in ARP, RP, and %R were observed only in the R-group (44+/-3.7, 93.7+/-1.5, 3.8+/-1.2, respectively; P<0.05). At baseline, the R-group showed an increase in %MC/area (8.3+/-0.7) and %MC-NF/area (5.2+/-2.6) with respect to the NR-group (5.1+/-0.5 and 2.3+/-0.4, respectively; P<0.05). After the diet, only the R-group showed a significant reduction of %MC/area and %MC-NF/area (4.4+/-0.5 and 2.2+/-0.4, respectively; P<0.001). Both ARP and RP significantly correlated with %MC/area and %MC-NF/area; %R showed a significant inverse correlation with both %MC/area and %MC-NF/area., Conclusions: In children with food allergy-related chronic constipation, an increase in both rectal MC density and spatial interactions between MCs and NFs correlates with anal motor abnormalities. These variables are significantly affected by the diet.

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

Pediatric gastrointestinal motility disorders represent some of the most challenging clinical conditions with largely undefined pathogenetic pathways and therefore limited therapeutic options. Herein, we provide an overview of the recent advances in treatment options for these disorders and their clinical impact. PubMed and Medline databases were searched for relevant articles related to the treatment of achalasia, esophageal atresia, gastroparesis, PIPO and constipation published between 2017 and 2022. In this article, we review and summarize recent advances in management of gastrointestinal motility disorders in children with a particular focus on emerging therapies as well as novel diagnostic modalities that help guide their application or develop new, more targeted treatments. Gastrointestinal motility disorders represent one of the most challenging conundrums in pediatric age and despite significant advances in investigative tools, the palette of treatment options remain limited. Overall, while pharmacological options have failed to bring a curative solution, recent advances in minimal invasive therapeutic and diagnostic techniques have emerged as potential keys to symptom and quality of life improvement, such as ENDOFLIP, POEM, cine-MRI, fecal microbiota transplantation. [ABSTRACT FROM AUTHOR]

The current increasing survival of children with severe central nervous system damage has created a major challenge for medical care. Gastrointestinal and nutritional problems in neurologically impaired children have been recently recognized as an integral part of their disease, often leading to growth failure and worsened quality of life for both children and caregivers. Nutritional support is essential for the optimal care of these children. Undernourished handicapped children might not respond properly to intercurrent diseases and suffer unnecessarily. On the other hand, restoring a normal nutritional status results in a better quality of life in many. The easiest and least invasive method to increase energy intake is to improve oral intake. However, oral intake can be maintained as long as there is no risk of aspiration, the child is growing well and the time required to feed the child remains within acceptable limits. When oral intake is unsafe, insufficient or too time consuming, enteral nutrition should be initiated. Damage to the developing central nervous system may result in significant dysfunction in the gastrointestinal tract and is reflected in impairment in oral-motor function, rumination, gastro-oesophageal reflux (GER), with or without aspiration, delayed gastric emptying and constipation. These problems can all potentially contribute to feeding difficulty in disabled children, carrying further challenging long-term management issues. [ABSTRACT FROM AUTHOR]

Background: Functional gastrointestinal disorders (FGIDs) are chronic or recurrent gastrointestinal symptoms without structural or biochemical abnormalities. FGIDs are multifactorial conditions with different pathophysiologic mechanisms including altered motility, visceral hyperalgesia, brain-gut disturbance, genetic, environmental and psychological factors. Although in most cases gastrointestinal symptoms are transient and with spontaneous resolution in infancy multiple dietary changes and pharmacological therapy are often started despite a lack of evidence-based data. Our aim was to update and critically review the current literature to assess the effects and the clinical appropriateness of drug treatment in early (occurring in infants and toddlers) FGIDs. Methods: We systematically searched the Medline and GIMBE (Italian Group on Medicine Based on Evidence) databases, according to the methodology of the Critically Appraised Topics (CATs). We included reviews, clinical studies, and evidence-based guidelines reporting on pharmacological treatments. Systematic reviews and randomized controlled trials (RCTs) concerning pharmacologic therapies in children with early FGIDs were included, and data were extracted on participants, interventions, and outcomes. Results: We found no evidence-based guidelines or systematic reviews about the utility of pharmacological therapy in functional regurgitation, infant colic and functional diarrhea. In case of regurgitation associated with marked distress, some evidences support a short trial with alginate when other non pharmacological approach failed (stepped-care approach). In constipated infants younger than 6 months of age Lactulose is recommended, whilst in older ages Polyethylene glycol (PEG) represents the first-line therapy both for fecal disimpaction and maintenance therapy of constipation. Conversely, no evidence supports the use of laxatives for dyschezia. Furthermore, we found no RCTs regarding the pharmacological treatment of cyclic vomiting syndrome, but retrospective studies showed a high percentage of clinical response using cyproheptadine, propanolol and pizotifen. Conclusion: There is some evidence that a pharmacological intervention is necessary for rectal disimpaction in childhood constipation and that PEG is the first line therapy. In contrast, for the other early FGIDs there is a lack of well-designed high-quality RCTs and no evidence on the use of pharmacological therapy was found. [ABSTRACT FROM AUTHOR]