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.

Non-Helicobacter pylori Gastric Intestinal Metaplasia in Children: A Series of Cases and Review of the Literature.

In the pediatric population, Gastric Intestinal Metaplasia (GIM) is a finding with unknown frequency and, more importantly, unknown clinical implications. The relationship between Helicobacter pylori (HP) infection and GIM is well documented, as well as an association between duodenogastric reflux and GIM. We present two cases of pediatric patients with GIM along with a review of the literature. The diagnosis of GIM may have adverse clinical implications and should be made with caution in a child. The association of GIM and adenoma/dysplasia and carcinoma is rarely seen in children, primarily because the time required for these to develop takes the individual into adulthood. Treatment, long-term consequences, and surveillance protocols are not well established in the pediatric population. Studies to evaluate the long-term natural history, treatment, and surveillance protocols in children with GIM are needed.

Pediatric Gastroesophageal Reflux Clinical Practice Guidelines: Joint Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition.

This document serves as an update of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) 2009 clinical guidelines for the diagnosis and management of gastroesophageal reflux disease (GERD) in infants and children and is intended to be applied in daily practice and as a basis for clinical trials. Eight clinical questions addressing diagnostic, therapeutic and prognostic topics were formulated. A systematic literature search was performed from October 1, 2008 (if the question was addressed by 2009 guidelines) or from inception to June 1, 2015 using Embase, MEDLINE, the Cochrane Database of Systematic Reviews and the Cochrane Central Register of Controlled Clinical Trials. The approach of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) was applied to define and prioritize outcomes. For therapeutic questions, the quality of evidence was also assessed using GRADE. Grading the quality of evidence for other questions was performed according to the Quality Assessment of Studies of Diagnostic Accuracy (QUADAS) and Quality in Prognostic Studies (QUIPS) tools. During a 3-day consensus meeting, all recommendations were discussed and finalized. In cases where no randomized controlled trials (RCT; therapeutic questions) or diagnostic accuracy studies were available to support the recommendations, expert opinion was used. The group members voted on each recommendation, using the nominal voting technique. With this approach, recommendations regarding evaluation and management of infants and children with GERD to standardize and improve quality of care were formulated. Additionally, 2 algorithms were developed, 1 for infants <12 months of age and the other for older infants and children.

Colon high-resolution manometry: using pressure topography plots to evaluate pediatric colon motility.

OBJECTIVES: Colon manometry is usually performed using the 8-pressure sensor water-perfused manometry system. High-resolution manometry (HRM), using closely spaced solid-state pressure recording sensors, provides more detailed information of gut luminal pressure changes, and, by displaying the HRM data as a pressure topography plot (PTP), helps with data interpretation. Our aim was to compare the colon and rectal luminal pressure data obtained using 8 pressure sensors and displayed as conventional line plot (CLP) with data obtained using a custom-made solid state manometry catheter with 36 pressure recording sensors and displayed as PTP. METHODS: We evaluated colon manometry patterns during fasting, response to meal, and bisacodyl stimulation in 10 patients with constipation and stool expulsion disorders. The data from 8 pressure sensors were displayed as CLP and data from 36 pressure sensors as PTP. Two gastroenterologists independently interpreted these studies. We calculated variability in interpreting colon, rectal, and anal manometry data. RESULTS: Intermode, interobserver, and intraobserver reliability were good to excellent for recognizing colon contraction patterns when data are displayed as PTP compared with when displayed as CLP, whereas the reliability for recognizing anal contractions were poor to excellent. CONCLUSIONS: Colonic and anal manometry patterns are easily recognized when HRM data are expressed as PTP. Obtaining information of colonic luminal pressure changes with rectum and anal pressure changes using HRM can help better understand the pathophysiology of pediatric constipation and stool expulsion disorders.

Endoscopic cricopharyngeal myotomy for management of cricopharyngeal achalasia (CA) in an 18-month-old child.

A 6-month-old patient presented with dysphagia and failure to thrive. Video fluoroscopic swallow study (VFSS), esophagogastroduodenoscopy, and manometry were diagnostic for CA. A gastrostomy tube was placed at 8 months. Botulinum toxin injection improved symptoms, but within 10 weeks symptoms returned. At 18 months, an uncomplicated endoscopic CPM was performed. A postoperative VFSS demonstrated cricopharyngeal bar resolution. Within 3 months, patient was feeding orally without a G tube. Pediatric CPA treatment options consist of dilation, botox, and transcervical CPM. To our knowledge, this is the youngest patient treated with endoscopic CPM. Intraoperative video and photographs are presented.

Identifying youth nonadherence in clinical settings: data-based recommendations for children and adolescents with inflammatory bowel disease.

BACKGROUND: To examine the validity of patient self-report of thiopurine adherence in pediatric inflammatory bowel disease (IBD) against an objective electronic monitoring adherence measure, and to investigate the role of youth and maternal involvement in remembering to take daily medications as predictors of medication adherence. METHODS: Fifty-one youths with IBD, ages 11-18 years, participated. Youths completed questionnaire assessments of their own and their maternal caregiver's involvement in remembering to take daily medications at baseline, completed monthly interviews assessing thiopurine adherence over the past week for a period of 6 months, and utilized a Medication Events Monitoring System (MEMS) electronic monitor for their thiopurine medication for 6 months. Participants were grouped into adherent (at least 80% of doses taken based on objective MEMS caps) or nonadherent for analyses. RESULTS: Youths who were nonadherent based on electronic monitoring overestimated their adherence by 23%, whereas adherent youths overestimated their adherence by only 2%, and as such patient self-report offered little utility in identifying youths who were nonadherent. Youths who reported high levels of involvement in remembering to take their medications were nearly eight times less likely to be nonadherent. CONCLUSIONS: The current findings provide evidence that clinicians who work with children and adolescents with IBD may benefit from modifying their approach to nonadherence screening. Asking about youth involvement in remembering daily medications may be more informative than asking them to recall their medication-taking behavior over the last week in identifying those at highest risk for nonadherence.

Do oro-anal transit markers predict which children would benefit from colonic manometry studies?

OBJECTIVES: The aim of the study was to compare oro-anal transit time (OTT) measured by radio-opaque markers with colon motility (CM) findings in children with chronic constipation and to assess clinical outcomes in children with chronic constipation evaluated by OTT and CM studies. METHODS: Twenty-four children with chronic constipation (12 girls; median age 12 years [3-18 years]; median symptoms 87 months [6-186 months]) who underwent OTT and CM studies were reviewed. The OTT was determined using commercially available Sitzmarks. Patients were studied for a median of 23 months (4-60 months) and outcomes reviewed. RESULTS: All 5 children with normal OTT had normal CM; however, only 47% (9/19) of children with slow OTT had an abnormal CM. The abnormal CM findings were total colonic pseudo-obstruction in 3 and left colonic pseudo-obstruction in 6 children. Of the 9 children with abnormal CM, 5 were managed surgically, 1 with medicine escalation, and 3 were lost to follow-up; all 6 children with known follow-up have more bowel movements and less soiling. Of the 15 children with normal CM, 10 were managed with medication escalation, 3 with behavioral intervention, and 2 surgically. Of these 15 children, 8 improved, 1 did not change, 2 worsened, and 4 were lost to follow-up. CONCLUSIONS: OTT studies may be helpful to predict which children should be referred for CM studies. Normal OTT studies may predict normal colon manometry; however, abnormal OTT studies may not predict abnormalities in colonic manometry in children with chronic constipation. Therefore, patients with slow transit marker studies should be assessed by colon manometry to evaluate colon neuromuscular integrity.

Capsule endoscopy performed across the pediatric age range: indications, incomplete studies, and utility in management of inflammatory bowel disease.

BACKGROUND: Capsule endoscopy (CE) is used increasingly to evaluate the small bowel in children. An upper GI series is recommended before CE to evaluate the risk of obstruction. Despite normal findings on an upper GI series, CE may still be incomplete. Although large adult studies have demonstrated the safety and diagnostic yield of CE, similar pediatric studies have not been available. OBJECTIVE: To identify factors associated with incomplete studies and the diagnostic yield in pediatric patients. DESIGN: Retrospective review of consecutive CE studies from February 2005 through June 2008. SETTING: Large tertiary children's hospital. PATIENTS: A total of 123 CE studies in 117 patients; median age 12.9 years (range 0.8-22.4 years). MAIN OUTCOME MEASUREMENTS: Demographic information, indication, placement technique, pre-CE imaging results, and cecal completion status were recorded. Risk factors were analyzed with bivariate and multivariate regression analysis. RESULTS: There were 27 (22%) incomplete studies; of these, there were normal pre-CE radiologic study findings in 12 (44%), and findings requiring medical, endoscopic, or operative intervention in 6. Of the 117 patients, CE produced a new diagnosis in 21 (18%). Abnormal findings on previous imaging (odds ratio [OR] 3.0; 95% CI, 1.2-8.0), endoscopic placement (OR 3.1; 95% CI, 1.1-8.4), and female sex (OR 3.3; 95% CI, 1.2-9.4) were associated with incomplete studies. LIMITATIONS: Retrospective, incomplete follow-up. CONCLUSIONS: CE may be performed in children as small as 11.5 kg, with 18% yield in all studies, and 28% in pediatric known inflammatory bowel disease. Capsule retention requiring retrieval did not pose life-threatening risk in our series, and CE may be used to identify disease-associated small-bowel stenosis.

Controversies in the treatment of gastroesophageal reflux disease in preterm infants.

Gastroesophageal reflux (GER) is common in preterm infants and usually is a physiologic phenomenon with little clinical consequence. GER resulting in clinical signs and symptoms is considered pathologic gastroesophageal reflux disease (GERD). Correlation of clinical signs and symptoms with GER has been poor in most studies. The efficacy of GERD therapy has not been studied systematically in preterm infants. Furthermore, GERD therapy, particularly with prokinetic agents and surgery, carries potential risks that must be considered before initiation of therapy. Alternative diagnoses, pretreatment diagnostic testing, and desired treatment outcomes should be considered before initiating GERD therapy. Cessation of empiric GERD therapy should be considered, particularly if treatment does not result in the desired clinical outcome.

A retrospective assessment of magnetic resonance cholangiopancreatography in children.

OBJECTIVE: To evaluate the utility of magnetic resonance cholangiopancreatography (MRCP) in children and to compare MRCP with direct cholangiopancreatography (CP). MATERIALS AND METHODS: We performed an unblinded, retrospective chart review of 32 children (ages 0-18 years, 17 male) who underwent MRCP between January 2002 and June 2005. MRCP, endoscopic retrograde cholangiopancreatography (ERCP), percutaneous fluoroscopic or intraoperative studies of the pancreatobiliary tree, and clinical outcomes were evaluated. RESULTS: Seventeen (52%) children had MRCP alone, 15 (48%) had both MR and direct CP. MRCP results correlated with other evaluative methods in 14/15 (93%) cases. There was 1 false positive (anomalous pancreatic duct union) and 0 false negatives for anatomic abnormalities. Therapeutic intervention was performed in 7 of 28 children initially evaluated by MRCP (2 sphincter of Oddi dysfunction, 2 choledocholithiasis, 2 primary sclerosing cholangitis, 1 congenital hepatic cysts) and 1 of 4 children initially evaluated by ERCP (primary sclerosing cholangitis). All 17 children initially evaluated by MRCP had no change in clinical status to suggest a missed anatomic lesion or therapeutic opportunity. CONCLUSIONS: In this retrospective study, MRCP was sensitive and specific in identifying anatomic abnormalities of the pancreatobiliary tree in children. MRCP should be considered before direct CP to evaluate anatomic abnormalities of the pancreatobiliary tree.

Treatment options in pediatric GERD.

Gastroesophageal reflux (GER) is a common physiologic phenomenon in infants and children. GER that results in symptoms or complications--hence the evolution to GER disease (GERD)--warrants targeted evaluation and appropriate treatment. Judicious use of acid-suppression therapy remains the mainstay of pharmacologic treatment of GERD. However, recognition of treatment goals and potentials risks of acid suppression must be considered prior to initiation of therapy. The role of surgical intervention for GERD remains limited.

Distension during gastroesophageal reflux: effects of acid inhibition and correlation with symptoms.

We studied spontaneous gastroesophageal reflux (GER)-induced esophageal distension using ultrasound imaging and its role in the genesis of esophageal symptoms before and during esomeprazole therapy. Ten controls and 10 GER disease (GERD) patients were studied by combined impedance, esophageal pH, manometry, and ultrasonography before and during esomeprazole therapy. Physiological data and symptoms were recorded for 2 h following a standardized meal. From ultrasound images, the esophageal cross-sectional area (CSA) at the peak of GER-induced distension was determined and compared between controls vs. patients, symptomatic vs. asymptomatic GER episodes, and before vs. during esomeprazole in GERD patients. The mean lumen CSA is greater in the patients than controls (271 +/- 71 mm(2) vs. 163 +/- 56 mm(2), P = 0.001) but not different among asymptomatic reflux episodes, and those associated with regurgitation (290 +/- 110 mm(2)) or heartburn (271 +/- 67 mm(2)). Eight chest pain episodes associated with reflux revealed a tendency toward larger mean esophageal distension (459 +/- 40 mm(2)) compared with asymptomatic reflux (268 +/- 70 mm(2), P = 0.058). Following esomeprazole treatment, most GER episodes were nonacidic and asymptomatic except in two patients in whom cyclical reflux was associated with large esophageal distensions. Esomeprazole did not alter the lumen CSA during GER. Esophageal distension is greater in the GERD subjects compared with controls; however, it is unlikely that the GER-induced distension of the esophagus plays a significant role in the genesis of heartburn sensation. Esomeprazole therapy does not alter the GER-induced distension of the esophagus.

The use of magnetic resonance cholangiopancreatography in children.

Magnetic resonance cholangiopancreatography (MRCP) is a noninvasive method to evaluate a wide variety of pancreatobiliary disorders. These disorders include choledochal cyst, cholelithiasis, choledocholithiasis, biliary atresia, Caroli's disease, primary sclerosing cholangitis, disorders of the pancreatobiliary junction, pancreas divisum, and pancreatic duct abnormalities related to chronic pancreatitis. The use of MRCP in children is increasing as experience with MRCP grows, and its technological accuracy rivals that of endoscopic evaluation. We review the current state of MRCP use in children.

Eosinophilic esophagitis -- a mimic of GERD.

Eosinophilic esophagitis (EE) is characterized by eosinophilic infiltration of the esophageal mucosa and results in clinical signs and symptoms that may be indistinguishable from those of gastroesophageal reflux disease (GERD). While demographic, clinical, and endoscopic features may be suggestive of EE, esophageal biopsy with tissue eosinophils averaging 24 per 400 x microscopic field remains the most specific diagnostic criterion. Previously rare, EE has been diagnosed in adults and children with increased frequency over the last decade; it appears to be a chronic disease and has a yearly incidence approximating 1:10,000 in the pediatric population. Dietary and respiratory antigen exposure with subsequent production of inflammatory chemokines is essential for development of EE in animal models of the disease. In humans, glucocorticoids and elimination of relevant dietary antigens have proved efficacious treatments for EE, resolving the disease at the mucosal level. Other therapies, including montelukast, partial dietary elimination, and bouginage have reduced symptoms without affecting mucosal inflammation. Evidence-based guidelines for the management of EE are not currently available. Current medical practice involving the management of reflux merits awareness and understanding of this emerging mimic. We present a review of the current understanding of this disorder.

Common cavity pressure during gastroesophageal reflux: reassessment using simultaneous pressure, impedance, and ultrasound imaging.

An increase in intraesophageal pressure during transient lower esophageal sphincter (LES) relaxation [referred to as common cavity (CC) pressure] is thought to be a marker of gastroesophageal reflux (GER). Multiluminal impedance (MII) measurement is a sensitive marker of reflux entry into the esophagus during GER. We recorded GER using esophageal pressure, pH, impedance, and intraluminal ultrasound (US) images to understand the genesis of the esophageal CC pressure. Nine normal subjects underwent simultaneous MII/pH/pressure and US image recording of the esophagus for 2 h following a standardized meal. MII and pressure transducers were located at 5 and 15 cm above the LES. The US transducer and pH sensors were also placed at 5 cm above the LES. Refluxate entry into the esophagus by MII criteria was determined relative to the onset of CC pressure wave. Esophageal lumen cross-sectional area (CSA) and muscle CSA during GER were determined from the US images. Eighty liquid GER episodes identified using MII criteria, of which 55 were clearly associated with CC pressure waves, were analyzed. The GER reached 15 cm above LES in 49 of 55 (89%) by MII criteria, but the CC pressure wave was observed at 5 and 15 cm during all episodes. The propagation of the CC pressure wave was simultaneous between 5 and 15 cm during 49 of 55 (89%) of the GER episodes, but reflux entry by MII criteria was retrograde during 53 of 55 (96%) of these episodes. During 5 air-reflux episodes, MII showed a simultaneous reflux entry between the 5- and 15-cm site, however, the CC pressure preceded reflux entry during all of these episodes. There was poor correlation between the luminal CSA and the magnitude of CC pressure (R(2) = 0.144). US images revealed a close temporal correlation between CC pressure and the increase in esophageal muscle thickness and muscle CSA (markers of longitudinal muscle contraction). Disassociation between CC pressure and MII-detected reflux suggests that the onset of CC pressure is not due to GER. We speculate that longitudinal muscle contraction plays an important role in the genesis of CC pressure.