A multicenter registry study on percutaneous electrical nerve field stimulation for pediatric disorders of gut-brain interaction.

OBJECTIVES: Percutaneous electrical nerve field stimulation (PENFS) has demonstrated promise in single-center trials for pediatric abdominal pain-related disorders of gut-brain interaction (DGBI). Our aim was to explore efficacy of PENFS as standard therapy for DGBI in a registry involving multiple pediatric gastroenterology referral centers. METHODS: This was a multicenter, prospective open-label registry of children (8-18 years) undergoing PENFS for DGBI at seven tertiary care gastroenterology clinics. DGBI subtypes were classified by Rome IV criteria. Parents and patients completed Abdominal Pain Index (API), Nausea Severity Scale (NSS), and Functional Disability Inventory (FDI) questionnaires before, during therapy and at follow-up visits up to 1 year later. RESULTS: A total of 292 subjects were included. Majority (74%) were female with median (interquartile range [IQR]) age 16.3 (14.0, 17.7) years. Most (68%) met criteria for functional dyspepsia and 61% had failed ≥4 pharmacologic therapies. API, NSS, and FDI scores showed significant declines within 3 weeks of therapy, persisting long-term in a subset. Baseline (n = 288) median (IQR) child-reported API scores decreased from 2.68 (1.84, 3.58) to 1.99 (1.13, 3.27) at 3 weeks (p < 0.001) and 1.81 (0.85, 3.20) at 3 months (n = 75; p < 0.001). NSS scores similarly improved from baseline, persisting at three (n = 74; p < 0.001) and 6 months later (n = 55; p < 0.001). FDI scores displayed similar reductions at 3 months (n = 76; p = 0.01) but not beyond. Parent-reported scores were consistent with child reports. CONCLUSIONS: This large, comprehensive, multicenter registry highlights efficacy of PENFS for gastrointestinal symptoms and functionality for pediatric DGBI.

Inadequate Bowel Preparation in Pediatric Colonoscopy-Prospective Study of Potential Causes.

OBJECTIVES: Inadequate bowel preparation (IBP) for colonoscopy leads to missed diagnosis, longer anesthesia time, higher chance of complications and increased costs. Adult studies have demonstrated that patient characteristics such as male gender and obesity are associated with IBP. Little is known about factors affecting bowel preparation in children. Our aim was to determine factors associated with IBP in children. METHODS: We prospectively enrolled children undergoing outpatient colonoscopy. Quality of bowel preparation was assessed using Boston Bowel Preparation Scale (BBPS) score (range 0-9). Data collected included patient demographics, indication, and type of insurance. Patients were divided into two groups based on BBPS score-adequate (BBPS score > 5) and inadequate (BBPS score < 5) and groups were compared using Student t-test and chi-square test. Possible predictors were analyzed using multivariate logistic regression models. RESULTS: A total of 334 children were prospectively enrolled of whom 321 were studied further (age range 2-18 years; mean age 12.4 years; 60.4% female; 85.9% Caucasian). The mean BBPS score was 6.8 (standard deviation of ±2). IBP was reported in 12.8% (41/321). Multivariable logistic regression analysis did not show statistical differences between the groups in studied patient factors including age, gender, obesity, race, insurance type, and indication for colonoscopy. CONCLUSION: Contrary to several adult studies, the results of our prospective study did not show any relationship between examined patient factors and IBP in children. Interestingly, IBP was less prevalent in our pediatric study compared to published adult data (12.8% vs 20-40%).

Pediatric bowel preparation: Sodium picosulfate, magnesium oxide, citric acid vs polyethylene glycol, a randomized trial.

BACKGROUND: Bowel preparation in children can be challenging. AIM: To describe the efficacy, safety, and tolerability of sodium picosulfate, magnesium oxide, and citric acid (SPMC) bowel preparation in children. METHODS: Phase 3, randomized, assessor-blinded, multicenter study of low-volume, divided dose SPMC enrolled children 9-16 years undergoing elective colonoscopy. Participants 9-12 years were randomized 1:1:1 to SPMC ½ dose × 2, SPMC 1 dose × 2, or polyethylene glycol (PEG). Participants 13-16 years were randomized 1:1 to SPMC 1 dose × 2 or PEG. PEG-based bowel preparations were administered per local protocol. Primary efficacy endpoint for quality of bowel preparation was responders (rating of 'excellent' or 'good') by modified Aronchick Scale. Secondary efficacy endpoint was participant's tolerability and satisfaction from a 7-item questionnaire. Safety assessments included adverse events (AEs) and laboratory evaluations. RESULTS: 78 participants were randomized, 48 were 9-12 years, 30 were 13-16 years. For the primary efficacy endpoint in 9-12 years, 50.0%, 87.5%, and 81.3% were responders for SPMC ½ dose × 2, SPMC 1 dose × 2, and PEG groups, respectively. Responder rates for 13-16 years were 81.3% for SPMC 1 dose × 2 and 85.7% for PEG. Overall, 43.8% of participants receiving SPMC 1 dose × 2 reported it was 'very easy' or 'easy' to drink, compared with 20.0% receiving PEG. Treatment-emergent AEs were reported by 45.5% of participants receiving SPMC 1 dose × 2 and 63.0% receiving PEG. CONCLUSION: SPMC was an efficacious and safe for bowel preparation in children 9-16 years, with comparable efficacy to PEG. Tolerability for SPMC was higher compared to PEG.

Clinical factors and high-resolution manometry predicting response to surgery for achalasia in children.

BACKGROUND: Esophageal achalasia is an uncommon condition in children. Although many interventions exist for the management of this disorder, esophageal (Heller) myotomy offers one of the most durable treatments. Our institution sought to review patients undergoing Heller myotomy concentrating on preoperative clinical factors that might predict postoperative outcomes. MATERIALS AND METHODS: All patients from January 1, 2007, to December 31, 2016, who underwent surgical treatment for achalasia at our tertiary pediatric hospital were identified and included in the study cohort. Electronic medical records for these patients were reviewed for clinical presentation variables, nonsurgical preoperative treatment, surgical approach, clinical response to surgery, need for postoperative treatment for ongoing symptoms, and high-resolution manometry (HRM) data. RESULTS: Twenty-six patients were included in the study, and all underwent myotomy with partial fundoplication (median age: 14.4 y [interquartile range 11.6-15.5]). At a median follow-up of 9.75 mo (interquartile range 3.5-21 mo), 16 (61.5%) patients reported good resolution of their dysphagia symptoms with surgery alone. Two patients (7.7%) had perforation of the gastrointestinal tract requiring surgical intervention. Eight patients (30.8%) required additional treatment for achalasia, with 5 (19.2%) of these undergoing additional surgery or endoscopic treatment. Patients who had preoperative dilation did not have good resolution of their dysphagia (n = 2; P = 0.037). Two of four patients undergoing postoperative dilation had preoperative dilation. None of these patients underwent preoperative manometry. There was a statistically significant difference in the ages of patients who required postoperative intervention and those who did not (14.1 versus 15.2 y old, respectively; P = 0.043). In patients who reported improvement of gastroesophageal reflux disease/reflux type symptoms after Heller myotomy, lower esophageal residual pressure (29.1 versus 18.7 mmHg; P = 0.018) on preoperative HRM was significantly higher than in those who did not report improvement after surgery. Higher upper esophageal mean pressure (66.6 versus 47.8 mmHg; P = 0.05) also predicted good gastroesophageal reflux disease/reflux symptom response in a similar manner. CONCLUSIONS: Current analysis suggests that preoperative dilation should be used cautiously and older patients may have a better response to surgery without need for postoperative treatment. In addition, preoperative HRM can aid in counseling patients in the risk of ongoing symptoms after surgery and may aid in determining if a fundoplication should be completed at the index procedure. Further research is needed to delineate these factors. LEVEL OF EVIDENCE: Level III.

Incidence of Low Seroimmunity to Hepatitis B Virus in Children With Inflammatory Bowel Disease.

OBJECTIVES: Patients with inflammatory bowel disease (IBD) often receive immunosuppressive therapy, which may make them vulnerable to infections such as hepatitis B. We hypothesized that hepatitis B virus titers are low in the vaccinated pediatric population with IBD. The aims of our study were to identify the incidence of lower titers of hepatitis B surface antibody (HBsAb) and determine which patient factors may be associated with lower HBsAb titers. METHODS: Patients with diagnosis of IBD, ages 5 to 18 years, were prospectively enrolled. Patients were confirmed to have had a full series of hepatitis B vaccination. Quantitative serum HBsAb titers were measured and logistic regression analysis with independent variables of age, sex, race, disease phenotype, surgery, medications and a dependent variable of adequate HBsAb titers (> 10 mIU/mL) was performed. RESULTS: Of the 116 patients enrolled, 57 were boys and 59 were girls. 75 patients had a diagnosis of Crohn disease; 32 had a diagnosis of ulcerative colitis; and 9 patients had been diagnosed as having indeterminate colitis. At the time of the study, 15 patients were taking corticosteroid, 66 on an immunomodulator, and 53 on a biologic. Sixty percent of patients in the 5- to 10-year age group had protective titers versus 22% to 27% in the older groups, P = 0.04. Only 28% of the 116 patients had HBsAb titers of >10m IU/mL. Twenty percent of the patients taking corticosteroids, 27% taking immunomodulators, and 24% taking biologics were found to be seroimmune. CONCLUSIONS: Nearly two-thirds of pediatric patients with IBD have low titers against hepatitis B virus. Titers were highest in the younger patients. No patient-specific variable, such as the use of immunosuppressants, appeared to influence these low titers.

Contemporary short- and long-term outcomes in patients with unremitting constipation and fecal incontinence treated with an antegrade continence enema.

PURPOSE: The primary aim of this study is to determine the natural history of patients who undergo an antegrade continence enema (ACE) procedure including complications, functional results, and long-term outcomes. METHODS: Patients aged 3-18years who underwent an ACE procedure from 2008 to 2015 for unremitting constipation and fecal incontinence with at least thirty day follow-up were included. Patients with congenital anatomic disorders of the spine, rectum, and anus were excluded. RESULTS: A total of 93 patients were included in the analysis with an average age of 10+/-4years and follow-up of 26+/-41months. The ACE procedure was rapidly effective, with 99% of patients experiencing improvement at 1month. At the end of follow-up, 83% of patients had normal bowel function, and 95% of patients noted improvement. Amongst patients with at least 24months of follow-up (n=51), 43% successfully stopped using their ACE at an average of 40+/-27months. Overall morbidity was 55%, mostly related to minor complications. However, 13% of patients required an additional operation. CONCLUSION: The ACE procedure is very successful in the treatment of unremitting constipation with fecal incontinence in appropriately selected patients. LEVEL OF EVIDENCE: Level IV.

Effect of Octreotide on Colonic Motility in Pediatric Patients With Chronic Recalcitrant Constipation.

OBJECTIVE: The aim of the present study was to study the effect of octreotide on colonic motility in pediatric patients with recalcitrant chronic constipation/encopresis and other suspected colonic motility disorders. METHODS: This was a nonrandomized, single-center, open-label, prospective study evaluating the effect of a single subcutaneous dose of octreotide on colonic motility. RESULTS: Thirteen patients (5 boys) were enrolled in the study. The age range was 4.6 to 16.2 years. Eleven patients (84%) had normal colonic manometry and 2 patients (16%) had colonic neuropathy. Motility Index (MI) (mmHg) for the 15 minutes before and after octreotide infusion was 6.03 ±â€Š1.26 (95% confidence interval [CI] 5.35-6.72) and 5.32 ±â€Š1.66 (95% CI 4.42-6.23), respectively, with P value of 0.08. MI for the 30 minutes before and after octreotide infusion was 6.89 ±â€Š1.37 (95% CI 6.14-7.64) and 6.71 ±â€Š1.47 (95% CI 5.91-7.52), respectively, with P value of 0.55. MI for the 45 minutes before and after octreotide infusion was 7.73 ±â€Š1.32 (95% CI 7.01-8.45) and 7.53 ±â€Š1.38 (95% CI 6.78-8.28), respectively, with P value of 0.8. CONCLUSION: Our study showed that the administration of octreotide resulted in no significant changes in colonic MI in pediatric patients with chronic recalcitrant constipation.

Neuroenteric Staining as a Tool in the Evaluation of Pediatric Motility Disorders.

The diagnosis of enteric neuromuscular disorders has come a long way since the first description of an enteric neuropathic disorder by the Danish physician Harald Hirschsprung in 1886. Advances in specialized enteric histopathological staining techniques have made it possible to identify subtle neuropathies and myopathies that cause intestinal motility disorders, from the common and now better understood and relatively easily diagnosed Hirschsprung's disease to the less common and more severe and not well-characterized chronic idiopathic intestinal pseudoobstruction, which continues to present a diagnostic challenge to the gastroenterologist and histopathologist alike. This article will discuss the common gastrointestinal motility disorders and some of the specialized histological stains, such as the relatively common enzyme stain, acetylcholinesterase, used to diagnose Hirschsprung's disease; advanced tinctorial stains, such as Masson trichrome, which may aid in diagnosis of enteric myopathies causing pseudoobstruction; and immunohistochemical stains such as C-Kit or PG 9.5, which may aid in the diagnosis of enteric neuropathies causing pseudoobstruction.

Comparing bedside methods of determining placement of gastric tubes in children.

PURPOSE: The purpose of this study was to compare the accuracy and predictive validity of pH, bilirubin, and CO2 in identifying gastric tube placement errors in children. DESIGN AND METHODS: After the tube was inserted into 276 children, the CO2 monitor reading was obtained. Fluid was then aspirated to test pH and bilirubin. RESULTS: Lack of ability to obtain tube aspirate was the best predictor of NG/OG placement errors with a sensitivity of 34.9% and a positive predictive value of 66.7%. Measuring pH, bilirubin, and CO2 of tube aspirate was less helpful. PRACTICE IMPLICATIONS: Healthcare providers should suspect NG/OG tube misplacement when no fluid is aspirated.

Quality of life in pediatric patients with unremitting constipation pre and post Malone Antegrade Continence Enema (MACE) procedure.

OBJECTIVE: The primary aim of this study was to determine if there is a change in the quality of life in pediatric patients with unremitting functional constipation and/or encopresis after undergoing a MACE procedure. METHODS: Patients, ages 5 to 18 years with unremitting constipation and a normal evaluation, including anorectal manometry and colonic manometry, who opted to undergo a MACE procedure were contacted to participate in the study. Patients with congenital anorectal malformations as well as spinal cord disorders were excluded from the study. The patient's parent/guardian completed the PedsQL(TM) Generic Core Scales QOL survey prior to the operation, 6 months, and 12 months after the procedure. RESULTS: A total of 15 consecutive patients meeting protocol criteria were recruited within a period of 20 months. The mean age at the MACE procedure was 9.8 years (range 7.0-11.1). 5 patients were female. The mean QOL score pre-MACE was 64.1. At 6 months post-MACE the mean overall QOL score was 90.2, and it was 92.0 at 12 months. All 15 patients at the 6 month follow up had significant improvement in their QOL (p=1.9 × 10(-7)) and all subcategories of QOL were significantly improved as well. CONCLUSIONS: A MACE procedure is of benefit to otherwise normal pediatric patients who have unremitting functional constipation with failure of medical treatment. Our patients had a significant improvement in all QOL categories and overall QOL.

Vomiting.

Vomiting can be the presenting symptom of a variety of disorders, ranging from self-limited diseases to life-threatening diseases. The causes of vomiting vary with age of presentation, and pediatricians should develop the skill to identify serious conditions at the earliest stage based on the age of presentation. Bilious emesis at any age is a sign of intestinal obstruction until proven otherwise and needs immediate attention. Vomiting is not always due to a GI disorder, and pediatricians should look for causes outside the GI tract if no GI disease is identified.

Can colonic manometry studies be done on the day of colonic motility catheter placement?

BACKGROUND AND AIMS: Colonic manometry has been used to assess colonic neuromuscular integrity in pediatric patients with severe constipation unresponsive to standard medical therapy and to tailor their treatment plans. There are presently no available standard protocols for conducting colonic manometry studies. The aim of the present study was to determine whether colonic manometry studies can be conducted on the same day the colonic motility catheters are placed and to compare the effects of inhaled sevoflurane versus intravenous propofol, used during catheter placement, on colonic motility. METHODS: Twenty patients, randomized to receive sevoflurane or propofol during catheter placement, underwent colonic manometry on the day of catheter placement as well as the day after. The total motility index (MI), change in MI in response to a meal and bisacodyl, and presence of high-amplitude propagating contractions were compared between the 2 studies for each patient. RESULTS: Ten patients were allocated to sevoflurane and 10 patients to propofol. A total of 8 (80%) patients in the sevoflurane group and 9 (90%) patients in the propofol group had no differences in their studies between days 1 and 2 when the tracings were interpreted manually for gross evidence of high-amplitude propagating contractions and gastrocolonic reflex. Similarly, there was no change in the total MI between studies done on days 1 and 2 in either sevoflurane (978 ± 232 vs 978 ± 184; P = 0.99) or propofol (968 ± 200 vs 1078 ± 227; P = 0.29) group. When comparing change in MI in response to a meal or bisacodyl between the 2 days, there was no statistical difference noted in either group. CONCLUSIONS: Colonic manometry studies can be conducted as early as 4 hours following catheter placement with either propofol or sevoflurane used for anesthesia.

Comparing methods of determining insertion length for placing gastric tubes in children 1 month to 17 years of age.

PURPOSE: The purpose was to compare three methods of predicting the gastric tube insertion length in children 1 month to 17 years of age: age-related, height-based (ARHB); nose-ear-xiphoid (NEX); and nose-ear-mid-umbilicus (NEMU). DESIGN AND METHODS: The design was a randomized controlled trial. Children were randomly assigned to the ARHB, NEX, or NEMU groups. Tubes placed high were considered to be misplaced. RESULTS: There were significant differences in percentages of correctly placed tubes, with ARHB and NEMU being more accurate than NEX. PRACTICE IMPLICATIONS: NEX should no longer be used as a gastric tube insertion-length predictor. Either ARHB or NEMU should be used.

Exploring potential noninvasive biomarkers in eosinophilic esophagitis in children.

BACKGROUND AND AIMS: Eosinophilic esophagitis (EE) continues to present clinical challenges, including a need for noninvasive tools to manage the disease. To identify a marker able to assess disease status in lieu of repeated endoscopies, we examined 3 noninvasive biomarkers, serum interleukin (IL)-5, serum eosinophil-derived neurotoxin (EDN), and stool EDN, and examined possible correlations of these with disease phenotype and activity (symptoms and histology) in a longitudinal study of children with EE. SUBJECTS AND METHODS: Children with EE were studied for up to 24 weeks (12 weeks on 1 of 2 corticosteroid therapies and 12 weeks off therapy). Twenty children with normal esophagogastroduodenoscopies with biopsies were enrolled as controls. Serum IL-5, serum EDN, and stool EDN were measured at weeks 0, 4, 12, 18, and 24 in children with EE, and at baseline alone for controls. Primary and secondary statistical analyses (excluding and including outlier values of the biomarkers, respectively) were performed. RESULTS: Sixty subjects with EE (46 [75%] boys, mean age 7.5 ±â€Š4.4 years) and 20 normal controls (10 [50%] boys, mean age 6.7 ±â€Š4.1 years) were included. Significant changes in serum EDN (significant decrease from baseline to week 4, and then rebound from week 4 to week 12) occurred. Serum EDN levels were stable after week 12. Serum IL-5 and stool EDN levels in subjects with EE were not statistically different from those of the control subjects when each time point for the cases was compared with the controls' 1-time measurement. CONCLUSIONS: Serum EDN levels were significantly higher in subjects with EE than in controls, and the results suggest a possible role, after additional future studies, for serum EDN in establishing EE diagnosis, assessing response to therapy, and/or monitoring for relapse or quiescence.

Esophageal pH monitoring with the BRAVO capsule: experience in a single tertiary medical center.

AIM: The aim of the present study was to report the global experience with placement, complication rate, and recording of esophageal pH using the BRAVO capsule at our institution. PATIENTS AND METHODS: We recorded the rate of any technical problems and complications during placement in all of the patients (ages 4-22 years) who received this device during a 2-year period. All of the patients undergoing esophagogastroduodenoscopy with the placement of BRAVO pH capsule were included in this analysis. We also examined the pH data recorded on days 1 and 2 for significant day-to-day variability during 2 days of pH monitoring. RESULTS: Two hundred eighty-nine BRAVO pH probes were placed from January 1, 2006 to December 31, 2008. At least 1 day of data was obtained in 278 patients (96.2%). Two days of data were obtained in 274 patients (94.8%). Of all of the reported complications, 1% occurred before deployment of the capsule, 4% occurred during deployment of the capsule, and 9% occurred after successful deployment of the capsule. One patient experienced a superficial esophageal tear that was associated with failure of the capsule to release from the delivery system. No patient requested removal of the capsule and all of the capsules detached within 14 days. In 9.12% of our patients, reflux index was normal on day 1 and abnormal on day 2. There was no statistically significant difference between reflux index recorded on day 1 versus day 2 (P = 0.686). CONCLUSIONS: The BRAVO pH capsule is easy to place, safe, and well tolerated by children. Performing a 48-hour study detected abnormal reflux in an additional 9% of our patients.

Effect of intravenous erythromycin on the colonic motility of children and young adults during colonic manometry.

PURPOSE: Erythromycin is successfully used as a gastroduodenal prokinetic agent. Given the limited available treatments for colonic dysmotility, further investigation into erythromycin's effect on colonic motility is warranted. We aimed to study the effect of erythromycin on colonic motility in pediatric patients with recalcitrant chronic constipation/encopresis and other suspected colonic motility disorders. METHODS: Patients referred for colonic manometry were eligible for enrollment. Fasting motility was recorded for 1 to 2 hours, then erythromycin lactobionate (EL), 3 mg/kg, was administered intravenously, and colonic motility was monitored for 1 to 2 hours after erythromycin. Manometry was then continued per routine. The motility index (MI) of pressure tracings at each pressure transducer was calculated for each patient for a period of 15 and 60 minutes before and after EL infusion. Change in MI was compared by Wilcoxon signed rank test. RESULTS: Twenty patients were enrolled. The most common indication was constipation with encopresis. Seventy percent of patients had normal colonic manometry, and 30% of patients demonstrated a neuropathy. Average MI for the 60-minute period before and after EL infusion were 254 +/- 74 mm Hg/h and 253 +/- 94 mm Hg/h, respectively (P = .55). Average MI for the 15-minute period before and after EL infusion were 64 +/- 23 mm Hg/15 min and 69 +/- 32 mm Hg/15 min, respectively (P = .45). CONCLUSIONS: Administration of intravenous EL resulted in no changes in colonic MI in pediatric patients referred for colonic manometry. Further studies on potential colokinetic agents are warranted in this population of patients.