Utility of colonic manometry in children with Hirschsprung disease.

OBJECTIVES: Abnormal motility of the residual colon has been reported in post-pull-through Hirschsprung disease (PT-HSCR) patients with persistent defecation problems. We reviewed the role of colonic manometry (CM) in the management of defecation disorders in these patients. METHODS: We retrospectively reviewed the medical record of PT-HSCR children who underwent CM for persistent symptoms of abnormal defecation. We reviewed their clinical course and its relation to CM findings. RESULTS: Thirty PT-HSCR patients underwent CM, of which five were diagnosed with transition zone pull-through and were excluded. Of the remaining 25 patients, 16 had colonic dysmotility, 8 had normal CM, and one had colonic hypermotility. In patients with dysmotility, five responded to ongoing medical management, three required surgical intervention (ileostomy), three remained symptomatic with medical management but not yet received surgical intervention, and five were lost to follow-up. In patients with normal CM, four responded to ongoing medical therapy, two required additional surgery (antegrade enema procedure), and two were lost to follow-up. The patient with hypermotility improved with adding loperamide. CONCLUSIONS: Colonic dysmotility can occur in PT-HSCR patients with persistent defecation problems. CM was helpful in delineating the degree of colonic neuromuscular dysfunction. CM results were used in conjunction with other clinical data to determine optimal management. Our findings support that medical management should first be optimized before consideration of colonic manometry and surgical interventions.

What is the Evidence for Over the Counter Laxatives to Treat Childhood Constipation?

PURPOSE OF REVIEW: Functional constipation is a common pediatric GI disorder that is responsible for a significant portion of pediatric office visits each year. It presents a significant stressor for patients, their families, and providers alike. There are a variety of over the counter agents available for treatment of pediatric constipation. RECENT FINDINGS: Osmotic laxatives, such as polyethylene glycol 3350 (PEG 3350) and lactulose, remain the most effective and safe therapy for both long and short term treatment of pediatric functional constipation. Stimulant laxatives, like Senna and Bisacodyl, probiotics, fiber preparations, enemas, and suppositories make excellent choices for adjunct therapies in specific clinical scenarios. There are multiple over the counter pharmacologic agents with various mechanisms of action that have demonstrated efficacy in pediatric functional constipation. These therapies are generally safe and well tolerated by patients.

Hirschsprung disease and other gastrointestinal motility disorders in patients with CCHS.

Congenital central hypoventilation syndrome (CCHS) is an autonomic nervous system dysfunction due to PHOX2B gene mutation. Little is known about gastrointestinal motility disorders in CCHS patients. This study aims to describe the spectrum of gastrointestinal motility disorders in CCHS and provide PHOX2B genotype-phenotype correlation with Hirschsprung Disease (HD). We reviewed the records of 72 CCHS patients seen at Children's Hospital Los Angeles from 1999 to 2019. Data collected included demographics, PHOX2B genotype, ventilator dependence, medical and surgical history, and gastrointestinal motility studies. Of the 72 patients, 31% had HD, 50% females, and 60% had 20/27 PARM. Rectosigmoid HD formed 73% of the cases whereas long segment (up to splenic flexure involvement) forms represented 23%. Four patients had total colonic aganglionosis, including one patient with 20/25 PARM genotype. One HD patient was identified with colonic myopathy in the residual segment. One patient was found to have achalasia type 1.Conclusion: Nearly one third of our CCHS patients had HD. Although most had 20/27 PARM, 2 patients had 20/25 PARM. Thus, CCHS patients with constipation are at risk for HD regardless of genotype. Colonic myopathy may coexist in treated HD with refractory constipation. Achalasia may occur in patients with CCHS. What is Known: • Patients with CCHS have motility disorders and present with esophageal dysmotility and constipation as a manifestation of their autonomic nervous system dysfunction. • About 20% of patients with CCHS have Hirschsprung disease and previously described to be associated with NPARM and 20/27 PARM genotype. What is New: • Thirty-one percent of CCHS patients in our series have Hirschsprung disease (HD). • HD, including the more severe total colonic aganglionosis was found in a patient with 20/25 PARM genotype suggesting that CCHS patients with constipation should be screened for HD regardless of genotype.

Hypomorphic SI genetic variants are associated with childhood chronic loose stools.

OBJECTIVE: The SI gene encodes the sucrase-isomaltase enzyme, a disaccharidase expressed in the intestinal brush border. Hypomorphic SI variants cause recessive congenital sucrase-isomaltase deficiency (CSID) and related gastrointestinal (GI) symptoms. Among children presenting with chronic, idiopathic loose stools, we assessed the prevalence of CSID-associated SI variants relative to the general population and the relative GI symptom burden associated with SI genotype within the study population. METHODS: A prospective study conducted at 18 centers enrolled 308 non-Hispanic white children ≤18 years old who were experiencing chronic, idiopathic, loose stools at least once per week for >4 weeks. Data on demographics, GI symptoms, and genotyping for 37 SI hypomorphic variants were collected. Race/ethnicity-matched SI data from the Exome Aggregation Consortium (ExAC) database was used as the general population reference. RESULTS: Compared with the general population, the cumulative prevalence of hypomorphic SI variants was significantly higher in the study population (4.5% vs. 1.3%, P < .01; OR = 3.5 [95% CI: 6.1, 2.0]). Within the study population, children with a hypomorphic SI variant had a more severe GI symptom burden than those without, including: more frequent episodes of loose stools (P < .01), higher overall stool frequency (P < .01), looser stool form (P = .01) and increased flatulence (P = .02). CONCLUSION: Non-Hispanic white children with chronic idiopathic loose stools have a higher prevalence of CSID-associated hypomorphic SI variants than the general population. The GI symptom burden was greater among the study subjects with a hypomorphic SI variant than those without hypomorphic SI variants.

Proceedings of the 2018 Advances In Motility and In NeuroGastroenterology: AIMING for the Future Single Topic Symposium.

OBJECTIVES: Motility and functional disorders are common in children and often debilitating, yet these disorders remain challenging to treat effectively. At the 2018 Annual North American Society for Pediatric Gastroenterology, Hepatology and Nutrition meeting, the Neurogastroenterology and Motility Committee held a full day symposium entitled, 2018 Advances In Motility and In NeuroGastroenterology - AIMING for the future. The symposium aimed to explore clinical paradigms in pediatric gastrointestinal motility disorders and provided a foundation for advancing new scientific and therapeutic research strategies. METHODS: The symposium brought together leading experts throughout North America to review the state of the art in the diagnosis and management of motility and functional disorders in children. Presentations were divided into esophageal, antral duodenal, and colorectal modules. Each module included oral presentations by experts in the respective fields, leading to thought-provoking discussions. There were 2 breakout sessions with small group discussions on select topics, focusing on defining scientific insights into the diagnosis and management of pediatric functional gastrointestinal and motility disorders in a systematic, segment-based approach. CONCLUSIONS: The field of neurogastroenterology has made remarkable progress in the last decade. The current report summarizes the major learning points from the symposium highlighting the diagnosis and promising therapies on the horizon for pediatric neurogastrointestinal and motility disorders.

Update on pediatric gastroparesis: A review of the published literature and recommendations for future research.

BACKGROUND: Due to scarcity of scientific literature on pediatric gastroparesis, there is a need to summarize current evidence and identify areas requiring further research. The aim of this study was to provide an evidence-based review of the available literature on the prevalence, pathogenesis, clinical presentation, diagnosis, treatment, and outcomes of pediatric gastroparesis. METHODS: A search of the literature was performed using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines with the following databases: PubMed, EMBASE, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, and Web of Science. Two independent reviewers screened abstracts for eligibility. KEY RESULTS: Our search yielded 1085 original publications, 135 of which met inclusion criteria. Most articles were of retrospective study design. Only 12 randomized controlled trials were identified, all of which were in infants. The prevalence of pediatric gastroparesis is unknown. Gastroparesis may be suspected based on clinical symptoms although these are often non-specific. The 4-hour nuclear scintigraphy scan remains gold standard for diagnosis despite lack of pediatric normative comparison data. Therapeutic approaches include dietary modifications, prokinetic drugs, and postpyloric enteral tube feeds. For refractory cases, intrapyloric botulinum toxin and surgical interventions such as gastric electrical stimulation may be warranted. Most interventions still lack rigorous supportive data. CONCLUSIONS: Diagnosis and treatment of pediatric gastroparesis are challenging due to paucity of published evidence. Larger and more rigorous clinical trials are necessary to improve outcomes.

Practice patterns of pediatricians and trainees for the management of functional constipation compared with 2006 NASPGHAN guidelines.

OBJECTIVES: The North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition has formulated guidelines for managing functional constipation. There have been no studies that have investigated how pediatricians apply the constipation guideline since it was revised in 2006. The purpose of this study was to examine how pediatricians approach functional constipation and how closely their approaches adhere to the guidelines. METHODS: An anonymous multiple-choice questionnaire was developed by general pediatricians and pediatric gastroenterologists. This was distributed to pediatricians and pediatric residents at 7 academic institutions, and to the American Academy of Pediatrics section on medical students, residents, and fellowship trainees mailing list. RESULTS: A total of 1202 responses were received (952 trainees, 250 attendings). Of these, 84.3% reported being unfamiliar/slightly familiar with the guidelines. The most common initial interventions for constipation without fecal incontinence included fluids (92.1%), fiber (89.5%), juice (77.7%), behavioral interventions (71.2%), follow-up (53.4%), and reducing constipating foods (50.1%). The most common initial interventions for constipation with fecal incontinence included bowel cleanout (73.4%), maintenance medication (70.0%), fluids (67.9%), behavioral interventions (67.6%), fiber (66.1%), and follow-up (57.8%). Osmotics were the most commonly prescribed as needed (83.0%) and maintenance medications (96.8%), with stimulants prescribed PRN by 35.6% and as maintenance by 16.8%. Some individuals (39.7%) reported concern that osmotics could result in dependence, addiction, or electrolyte imbalances, compared with 73.0% for stimulants. CONCLUSIONS: Our results show that more education regarding medication in functional constipation is necessary, including the use of medication reducing time to remission, the necessity of disimpaction, and misconceptions regarding adverse effects.

The value of fluoroscopic defecography in the diagnostic and therapeutic management of defecation disorders in children.

BACKGROUND: Defecography is a study to assess anorectal function during evacuation. OBJECTIVE: To investigate the value of fluoroscopic defecography in directing diagnostic and therapeutic management in children with defecation disorders. MATERIALS AND METHODS: We reviewed all fluoroscopic defecography studies performed (2003-2009) in children with defecation problems and normal anorectal motility studies. Results were classified into three groups: (1) normal pelvic floor function; (2) pelvic floor dyssynergia, including incomplete relaxation of pelvic musculature, inconsistent change in anorectal angle and incomplete voluntary evacuation; (3) structural abnormality, including excessive pelvic floor descent with an intra-rectal intussusception, rectocele or rectal prolapse. RESULTS: We included 18 patients (13 boys, median age 9.1 years). Indication for fluoroscopic defecography was chronic constipation in 56%, fecal incontinence in 22% and rectal prolapse in 22%. Defecography showed pelvic floor dyssynergia in 9 children (50%), a structural abnormality in 4 (22%) and normal pelvic floor function in 5 (28%). In 12 children (67%) the outcome of fluoroscopic defecography directly influenced therapeutic management. After defecography 4 children (22%) were referred for anorectal biofeedback treatment, 4 children (22%) for surgery, 2 children (11%) for additional MR defecography, and 1 child to the psychology department, and medication was changed in 1 child. In 6 children (33%) the result did not change the management. In 9 children (75%) the change of management was successful. CONCLUSIONS: Fluoroscopic defecography can be a useful tool in understanding the pathophysiology and it may provide information that impacts management of children with refractory defecation disorders.

Colonic manometry and colonic scintigraphy as a diagnostic tool for children with severe constipation.

OBJECTIVE: In adults, colonic manometry and colonic scintigraphy are both valuable studies in discriminating normal and abnormal colonic motility. The objective of this study was to compare the diagnostic yield and tolerability of colonic manometry and colonic scintigraphy in children with severe constipation. METHODS: Twenty-six children (mean age 11.4 years, 77% boys) who had received colonic manometry and colonic scintigraphy as part of a colonic motility evaluation were included. Manometry was performed as per department protocol. After swallowing a methacrylate-coated capsule containing indium-111, images were taken at 4, 24, and 48 hours, and geometric centers were calculated. Results of both tests were categorized in 3 groups: normal, abnormal function in the distal part of the colon, and colonic inertia. Cohen κ was used for the level of agreement. Patients and parents completed a questionnaire regarding their experience. RESULTS: Colonic scintigraphy showed normal transit time in 20%, delay in the distal colon in 48%, and colonic inertia in 32% of patients. Colonic manometry was normal in 40%, abnormal in the distal colon in 40%, and colonic inertia was diagnosed in 20%. The κ score was 0.34. All 5 patients with colonic inertia during manometry had a similar result by scintigraphy. Eighty-eight percent of patients preferred scintigraphy over manometry and 28% of parents preferred colonic manometry over scintigraphy. CONCLUSIONS: Colonic manometry and colonic scintigraphy have a fair agreement regarding the categorization of constipation. Scintigraphy is well tolerated in pediatric patients and may be a useful tool in the evaluation of children with severe constipation.

Efficacy of permanent gastric electrical stimulation for the treatment of gastroparesis and functional dyspepsia in children and adolescents.

PURPOSE: Permanent gastric electrical stimulation (GES) has been performed in adults as a treatment for gastroparesis and refractory nausea and vomiting in patients who have failed medical therapy. We assessed the feasibility and clinical outcomes of permanent GES in children. METHODS: Permanent GES was performed in 16 children (10 females/6 males), median age 15 years (range 4-19 years). All patients had chronic nausea and vomiting refractory to medical therapy and met ROME III criteria for functional dyspepsia. Symptoms, route for nutrition, and satisfaction with procedure were recorded before and after permanent GES. Statistical analysis was performed using paired Student's t test. RESULTS: After permanent GES, there was significant improvement in severity of vomiting (p=0.0001), frequency of vomiting (p=0.0003), frequency of nausea (p<0.0001), and severity of nausea (p<0.0001). At the time of follow-up, 13/16 were on oral feeds exclusively, two patients on oral plus G-tube feedings, and one patient on oral plus G-tube plus intermittent TPN. CONCLUSIONS: 1). Permanent GES improved health in children with functional dyspepsia and gastroparesis who fail medical therapy. 2). No serious adverse effects of permanent GES were noted. 3). Long-term efficacy and safety of GES therapy in children need to be established.

Ten-year experience using antegrade enemas in children.

OBJECTIVE: To describe a single-center, 10-year experience with the use of antegrade enemas. STUDY DESIGN: Retrospective analysis of 99 patients treated with antegrade enemas at Nationwide Children's Hospital. RESULTS: Study subjects (median age 8 years) were followed for a mean time of 46 months (range 2-125 months) after cecostomy placement. Seventy-one patients had the cecostomy placed percutaneously and 28 by surgery. Thirty-five patients had functional constipation and 64 patients an organic disease (spinal abnormalities, cerebral palsy, imperforate anus, Hirschsprung's disease). While using antegrade enemas, 71% became symptom-free, in 20 subjects symptoms improved, in 2 subjects symptoms did not change, and in 7 subjects symptoms worsened. Poor outcome was associated with surgical placement of the cecostomy (P < .001), younger age (P = .02), shorter duration of symptoms (P = .01), history of Hirschsprung's disease (P = .05), cerebral palsy (P = .03), previous abdominal surgery (P = .001), and abnormal colonic manometry (P = .004). In 88%, successful irrigation solution included use of a stimulant laxative, and subjects who used a stimulant did significantly better (P < .001) than subjects who started without a stimulant. In 13 patients, the cecostomy was removed 49.7 months after placement without recurrence of symptoms. Major complications occurred in 12 patients and minor complications in 47. CONCLUSIONS: Antegrade enemas represent a successful and relatively safe therapeutic option in children with severe defecatory disorders. Prognostic factors are identified.

Effect of amoxicillin/clavulanate on gastrointestinal motility in children.

AIM: The aim of the present study was to evaluate the effect of amoxicillin/clavulanate (A/C) on gastrointestinal motility. METHODS: Twenty consecutive pediatric patients referred for antroduodenal manometry received 20 mg/kg of A/C into the small bowel lumen. In 10 patients (group A), A/C was given 1 hour after and in 10 (group B), 1 hour before ingestion of a meal. Characteristics of the migrating motor complex, including presence, frequency, amplitude, and propagation of duodenal phase III and phase I duration and phase II motility index (MI), were evaluated 30 minutes before and after A/C administration. RESULTS: There were no statistically significant differences in age and sex between the 2 groups. Manometry studies were considered normal in 8 patients in each group. In group A, 2 patients developed duodenal phase III after receiving A/C, and no significant difference was found in the MI before and after the drug administration. In group B, 9 patients developed duodenal phase III (P <0.05 vs group A). All phase III occurred within a few minutes from the medication administration. Most duodenal phase III contractions were preceded by an antral component during fasting but never after the medication was administered in either of the 2 groups (P<0.001 vs fasting). In group B, the duration of duodenal phase I was shorter after drug administration (P<0.05). There was no significant difference in duodenal phase II MI before and after A/C administration for the 2 study groups. CONCLUSIONS: In children, administration of A/C directly into the small bowel before a meal induces phase III-type contractions in the duodenum, with characteristics similar to those present in the fasting state. These data suggest the possible use of A/C as a prokinetic agent. Further studies are needed to clarify its specific mechanism of action and the group of patients most likely to benefit from its use.

Effect of early immunomodulator use in moderate to severe pediatric Crohn disease.

BACKGROUND: The immunomodulators (IMs) 6-mercaptopurine and azathioprine decrease corticosteroid dependence and maintain remission in Crohn's disease (CD). We describe IM use in newly diagnosed pediatric CD, comparing outcomes of "early" versus "late" initiation of therapy. METHODS: Data were obtained from pediatric CD patients enrolled in a prospective, multicenter observational study. Moderate/severe disease patients treated with IM were compared for outcomes of remission, corticosteroid use, infliximab therapy, hospitalizations, and CD-related surgery based on timing of initiation of IM therapy. RESULTS: In all, 247 children met the criteria (60% male, mean age 11.9 years); 199 were treated with IM within 1 year of diagnosis; 150 between 0-3 months (early), 49 between 3-12 months (late). Both groups showed a decrease in corticosteroid use by 12 months, at which time proportionately fewer early group patients had received corticosteroids in the preceding quarter (22%) than late groups patients (41%)(P = 0.013). The number of hospitalizations per patient was also noted to be significantly lower in the early group over the 2-year follow-up (P = 0.03). No difference was noted in the rates of remission, infliximab use over time, or surgery. CONCLUSIONS: 80% of children with newly diagnosed moderate to severe CD are treated with IM within 1 year. Early IM use is associated with reduced corticosteroid exposure and possibly fewer hospitalizations per patient.