Thirumazhisai S. Gunasekaran

Safety and symptom improvement with esomeprazole in adolescents with gastroesophageal reflux disease.

Objectives: The primary objective was to assess the safety of esomeprazole 20 or 40 mg once daily in adolescents with clinically diagnosed gastroesophageal reflux disease (GERD). A secondary aim was to assess changes in GERD symptoms after esomeprazole therapy. Patients and Methods: In this multicenter, randomized, double-blind study, adolescents ages 12 to 17 years inclusive received esomeprazole 20 or 40 mg once daily for 8 weeks. Adverse events and changes in clinical parameters (eg, physical examination, laboratory measurements) were evaluated to assess safety. Patients or their parents or guardians scored symptom severity daily, and investigators scored overall GERD symptom severity every 2 weeks using a 4-point scale. Results: In the 148 adolescents with safety data, treatment-related and non–treatment-related adverse events were reported by 75% and 78% of patients in the esomeprazole 20- and 40-mg groups, respectively. Twenty-two patients (14.9%) experienced adverse events that were considered related to treatment; the most common were headache (8%, 12/148), abdominal pain (3%, 4/148), nausea (2%, 3/148), and diarrhea (2%, 3/148). No serious adverse events or clinically important findings in other safety assessments were observed. At baseline, 68% (100/147) had heartburn, 63% (93/147) had epigastric pain, 57% (84/147) had acid regurgitation, and 15% (22/147) had vomiting symptoms. Symptom scores decreased significantly in both the esomeprazole 20-mg and 40-mg groups by the final study week (P < 0.0001). Investigators rated 63.1% (94/149) of the patients as having moderate or severe symptoms at baseline; at the final visit, this percentage decreased significantly to 9.3% (13/140; P < .0001). Conclusions: In adolescent patients with GERD, esomeprazole 20 or 40 mg daily for 8 weeks was well tolerated, and GERD-related symptoms were significantly reduced from baseline values in both groups.

Esomeprazole for the Treatment of GERD in Infants Ages 1-11 Months.

Objectives: Gastroesophageal reflux disease (GERD) is present in pediatric patients when reflux of gastric contents causes troublesome symptoms and/ or complications. The present study evaluates the efficacy and safety of esomeprazole in infants ages 1 to 11 months with GERD. Methods: In this multicenter randomized, double-blind, placebo-controlled, parallel-group, treatment-withdrawal study, infants received open-label, weight-adjusted doses of esomeprazole (2.5–10 mg) once daily for 2 weeks. Infants with symptom improvement were randomized to esomeprazole (weight-adjusted doses [2.5–10 mg]) or placebo for 4 weeks. The primary endpoint was time to discontinuation owing to symptom worsening based on global assessments by the parent/guardian and physician. Adverse events were recorded. Results: Of the 98 patients enrolled, 81 (82.7%) experienced symptom improvement determined by physician global assessment (PGA) during open-label esomeprazole treatment; 80 entered the double-blind phase. During this phase, discontinuation rates owing to symptom worsening were 48.8% (20/41) for placebo-treated versus 38.5% (15/39) for esomeprazole-treated patients (hazard ratio 0.69; P = 0.28). Posthoc analysis of infants with symptomatic GERD (ie, no diagnostic procedure performed) revealed that time to discontinuation was significantly longer with esomeprazole than placebo (hazard ratio 0.24; P = 0.01); the complementary subgroup difference was not significant (hazard ratio 1.39; P = 0.48). Esomeprazole was well tolerated. Conclusions: The discontinuation rate owing to symptom worsening did not differ significantly between infants receiving esomeprazole versus those receiving placebo. Improved diagnostic criteria in this age group are needed to identify infants with GERD who may benefit from acid suppression therapy.OBJECTIVES Gastroesophageal reflux disease (GERD) is present in pediatric patients when reflux of gastric contents causes troublesome symptoms and/ or complications. The present study evaluates the efficacy and safety of esomeprazole in infants ages 1 to 11 months with GERD. METHODS In this multicenter randomized, double-blind, placebo-controlled, parallel-group, treatment-withdrawal study, infants received open-label, weight-adjusted doses of esomeprazole (2.5-10 mg) once daily for 2 weeks. Infants with symptom improvement were randomized to esomeprazole (weight-adjusted doses [2.5-10 mg]) or placebo for 4 weeks. The primary endpoint was time to discontinuation owing to symptom worsening based on global assessments by the parent/guardian and physician. Adverse events were recorded. RESULTS Of the 98 patients enrolled, 81 (82.7%) experienced symptom improvement determined by physician global assessment (PGA) during open-label esomeprazole treatment; 80 entered the double-blind phase. During this phase, discontinuation rates owing to symptom worsening were 48.8% (20/41) for placebo-treated versus 38.5% (15/39) for esomeprazole-treated patients (hazard ratio 0.69; P = 0.28). Posthoc analysis of infants with symptomatic GERD (ie, no diagnostic procedure performed) revealed that time to discontinuation was significantly longer with esomeprazole than placebo (hazard ratio 0.24; P = 0.01); the complementary subgroup difference was not significant (hazard ratio 1.39; P = 0.48). Esomeprazole was well tolerated. CONCLUSIONS The discontinuation rate owing to symptom worsening did not differ significantly between infants receiving esomeprazole versus those receiving placebo. Improved diagnostic criteria in this age group are needed to identify infants with GERD who may benefit from acid suppression therapy.OBJECTIVES Gastroesophageal reflux disease (GERD) is present in pediatric patients when reflux of gastric contents causes troublesome symptoms and/or complications. The present study evaluates the efficacy and safety of esomeprazole in infants ages 1 to 11 months with GERD. METHODS In this multicenter randomized, double-blind, placebo-controlled, parallel-group, treatment-withdrawal study, infants received open-label, weight-adjusted doses of esomeprazole (2.5-10 mg) once daily for 2 weeks. Infants with symptom improvement were randomized to esomeprazole (weight-adjusted doses [2.5-10 mg]) or placebo for 4 weeks. The primary endpoint was time to discontinuation owing to symptom worsening based on global assessments by the parent/guardian and physician. Adverse events were recorded. RESULTS Of the 98 patients enrolled, 81 (82.7%) experienced symptom improvement determined by physician global assessment (PGA) during open-label esomeprazole treatment; 80 entered the double-blind phase. During this phase, discontinuation rates owing to symptom worsening were 48.8% (20/41) for placebo-treated versus 38.5% (15/39) for esomeprazole-treated patients (hazard ratio 0.69; P = 0.28). Posthoc analysis of infants with symptomatic GERD (ie, no diagnostic procedure performed) revealed that time to discontinuation was significantly longer with esomeprazole than placebo (hazard ratio 0.24; P = 0.01); the complementary subgroup difference was not significant (hazard ratio 1.39; P = 0.48). Esomeprazole was well tolerated. CONCLUSIONS The discontinuation rate owing to symptom worsening did not differ significantly between infants receiving esomeprazole versus those receiving placebo. Improved diagnostic criteria in this age group are needed to identify infants with GERD who may benefit from acid suppression therapy.

Halothane hepatitis in children

Halothane hepatitis is now a well-recognized distinct entity in adults, but there prevails an often-taught “axiom” that halothane hepatitis “does not occur” in children. We describe 2 children who developed cholestatic hepatitis following halothane anesthesia. The first patient had no antecedent liver disease, and presented with anorexia, abdominal pain and delayed onset of jaundice after multiple halothane exposures. Halothane-specific antibodies were positive, and liver tests resolved completely. The second patient had antecedent liver disease and presented with delayed onset of unexplained high fevers for 10 days following a single halothane exposure. Gradually increasing cholestasis ensued in the absence of other causes of liver disease. Halothane antibodies were negative. These cases illustrate different clinical presentations of halothane hepatitis, such as delayed onset of jaundice or fever following halothane exposure. The difficulties in making a definitive diagnosis and the need to exclude other causes of liver disease are detailed. Risk factors and other presentations are discussed. While halothane hepatitis appears to be an uncommon entity in children, it does occur, and may present with manifestations less than fulminant hepatic failure. A high index of suspicion and a detailed history of the time sequence of events are necessary as the diagnosis is primarily clinical. Halothane-specific antibodies are helpful if positive. In any child developing unexplained jaundice or high fevers following halothane anesthesia, further exposures should be avoided and halothane-specific antibodies obtained.

Bannayan-Riley-Ruvalcaba Syndrome: Spectrum of Intestinal Pathology Including Juvenile Polyps

ABSTRACT Bannayan-Riley-Ruvalcaba syndrome (BRRS) is a disorder that includes juvenile polyposis as part of its pathologic spectrum, and it recently has been shown to share phenotypic and genotypic features with Cowdens disease. In existing literature, descriptions of intestinal pathology in patients with BRRS are relatively sparse and occasionally erroneous. We describe the intestinal pathology in multiple specimens from three children with BRRS. Examination of gastrointestinal biopsies from these children revealed predominantly colonic and rectal polyps with the histology of juvenile polyps. Additionally, two cases with clusters of ectopic ganglion cells within the lamina propria, one in a colonic polyp and one in a duodenal biopsy, and an atypical polyp were observed. Bannayan-Riley-Ruvalcaba syndrome should be included in the list of differential diagnostic considerations when a child or young adult presents with a juvenile polyp, particularly if unusual histologic features such as atypical polyps or ectopic ganglion cells are encountered.

Effects of esomeprazole treatment for gastroesophageal reflux disease on quality of life in 12- to 17-year-old adolescents: an international health outcomes study

BackgroundAlthough gastroesophageal reflux disease (GERD) is common in adolescents, the burden of GERD on health-related quality of life (HRQOL) in adolescents has not been previously evaluated. Therefore, the objective of the study was to examine the effect of GERD on HRQOL in adolescents.MethodsThis international, 31-site, 8-week safety study randomized adolescents, aged 12 to 17 years inclusive, with GERD to receive esomeprazole 20 or 40 mg once daily. The Quality of Life in Reflux and Dyspepsia questionnaire (QOLRAD), previously validated in adults, consists of 25 questions grouped into 5 domains: emotional distress, sleep disturbance, food/drink problems, physical/social functioning, and vitality. The QOLRAD was administered at the baseline and week-8 (final) visits.ResultsOf the 149 patients randomized, 134 completed the QOLRAD at baseline and final visits and were eligible for analysis of their HRQOL data. Baseline QOLRAD scores indicated GERD had a negative effect on the HRQOL of these adolescents, especially in the domains of vitality and emotional distress, and problems with food/drink. At the final visit, mean scores for all 5 QOLRAD domains improved significantly (P < .0001); change of scores (ie, delta) for all domains met or exceeded the adult QOLRAD minimal clinically significant difference standard of 0.5 units.ConclusionGERD had a negative effect on QOL in adolescents. After esomeprazole treatment, statistically and clinically significant improvements occurred in all domains of the QOLRAD for these adolescents.Trial RegistrationD9614C00098; ClinicalTrials.gov Identifier NCT00241501

Efficacy of lansoprazole in the treatment of GERD in children

Objective: To evaluate the safety of lansoprazole (Lan) in the 8|[ndash]|12 wk treatment (tx) of GERD in pts 1|[ndash]|12 yrs of age.

Difficult Esophageal Strictures: Role of Endoscopic Application of Topical Mitomycin

Difficult Esophageal Strictures: Role of Endoscopic Application of Topical Mitomycin T.S. Gunasekaran, Ganesh Namachivayam, Sharon Brown Some of the esophageal strictures are recalcitrant or difficult to dilate. There is limited literature on the topical mitomycin application (TMA). We report 2 patients with esophageal stricture who failed balloon dilation with triamcinalone injections (TI) or required frequent dilations. We describe a unique endoscopic method of TMA to the stricture area in these 2 patients and the outcome. Methods: Patient #1: Girl, 3 yrs, mid esophageal ‘‘dog leg like’’ stricture, from esophageal atresia post repair. Failed repeated TTS balloon dilation up to 12 mm with TI. Then dilation was done with Savary dilators followed by TI at the stricture site. After the dilation, mitomycin (0.3 mg/mL) was applied with an endoscopy brush soaked in the mitomycin solution, brush retracted, passed through the endoscope channel then opened and applied (rubbed) to the stricture site. This was repeated 5 times, applying mitomycin to different areas of the open mucosa. Post dilation esophagogram was done. CBC and chemistry panel were monitored. Patient #2: Male, 23 yrs, radiation stricture at mid esophagus, size about 9 mm. Required TTS dilation and TI. Stricture opened up but required two monthly dilation and TI. Subsequently TTS dilation, TI and TMA was done as above. Post procedure esophagram was not done but blood tests as above were done. Results: Patient #1: Total of 8 dilations was done, starting with 8 mm and increased up to 15 mm. There was no post procedure pain. There was ‘‘submucosal’’ perforation with the initial dilations which healed within 24 hours with conservative treatment. Follow up done for 13 months from the initial TMA. The frequency of dilations improved from every 3 weeks to 3 months. Predilation size at beginning about 5 mm diameter and now stricture is 9 mm. Patient can swallow solid foods well and is growing normally. Blood tests were normal. Patient #2: Had one TTS dilation followed by TI. TMA done as above. There was no post procedure pain or clinical evidence of perforation. He had no recurrence of symptoms for three months. Blood tests were normal. Conclusion: Topical mitomycin application after dilation should be considered for recalcitrant/resistant esophageal strictures. Endoscopy brush can be used to apply the mitomycin at the stricture site after dilation. We found this to be a safe method of treatment in our limited experience. Further studies are required with more patients and longer follow up to confirm the efficacy and safety of TMA. W1309 Histologic and Serologic Correlates of Patients with IBD: How Helpful Is Histology? Marek Lukacik, Janet M. Poulik, Ronald L. Thomas, Vasundhara Tolia Diagnosis of Crohn’s disease (CD) is based on a combination of location, laboratory, endoscopic and histologic findings. Although non-caseating granulomas are a hallmark of CD, focal or patchy inflammation in any area of the bowel is also considered to favor CD. Non specific histologic changes in upper GI tract can occur infrequently in ulcerative colitis (UC). Our aim was to discern if CD is overdiagnosed due to such nonspecific histologic markers when serology or endoscopy suggests UC. Methods: A retrospective chart review was performed in patients with chronic inflammatory bowel disease (CIBD) for IBD serology (ANCA and ASCA status), upper and lower endoscopy. Histology was blindly reviewed by pathologist to determine CD or UC based on changes in esophagus, stomach, duodenum and colon. Besides granulomas, lymphocytic inflammation in mucosa and submucosa or focal inflammation was considered suggestive of CD. Results: Charts of 41 patients (20 M and 21 F) were reviewed. Of these 37 were classified as CD based on histology and 4 were classified as UC, even though grossly only colon was involved in most. IBD serology was done 25/37 CD patients. Of these ASCA was positive in 6, ANCA in 11 and Omp-C in 1 patient and was negative in 7 patients. On esophageal histology only 13 had chronic focal inflammation, 20 had GER type inflammation, 2 had granulomas and 6 were normal. In the stomach, 9 had chronic inflammation, 5 acute inflammation 13 had granulomas and 11 were normal. In the duodenum 7 had chronic inflammation, 4 acute inflammation and 26 were normal. Of the 4 diagnosed to have UC, IBD serology was positive for ANCA in all. On histology, 2 had GER type changes and 2 had non-specific inflammation in esophagus. In the stomach, 3 had non-specific inflammation whereas in the duodenum, 1 had chronic inflammation, 1 had acute inflammation and 2 had normal histology. Conclusions: We conclude that minor histologic abnormalities of the upper GI tract should not be overread as being consistent with CD without clinical, endoscopic and serologic correlation, as otherwise, CD would be overdiagnosed. This has practical implications in the long-term management of medically refractory patients with UC, as stigma of CD label prevents consideration of surgery even when appropriate.

Detailed histologic evaluation of eosinophilic esophagitis in pediatric patients presenting with dysphagia or abdominal pain and comparison of the histology between the two groups

EoE in children presents with four main symptoms. Most common symptoms exhibited by our clinic population are dysphagia (D) and abdominal pain (AP). Despite similar treatments, we found in an earlier study that the outcomes between these two groups were different. Therefore, we investigated if there exist any histological differences between these groups that could further our knowledge of EoE. Aim. To compare esophageal histology in detail, apart from the eosinophil count, between EoE-D and EoE-AP. Method. Biopsies of patients with EoE-D and EoE-AP were reevaluated for 10 additional histological criteria, in addition to the eosinophil count. Results. Both groups had 67 patients; peak mean eosinophil was 33.9 and 31.55 for EoE-D and EoE-AP (p < 0.05). Eosinophilic microabscesses, superficial layering of eosinophils, and epithelial desquamation were twice as common and significant in EoE-D group than EoE-AP. Eosinophil distribution around rete pegs was also significantly higher in EoE-D group. The remaining criteria were numerically higher in EoE-D, but not significant, with the exception of rete peg elongation. Conclusion. EoE-D patients have significantly higher eosinophils compared to EoE-AP, and the level of inflammation as seen from eosinophil microabscesses, superficial layering, desquamation, and the distribution around rete pegs is significantly higher.

Continuous 48-hour Wireless Esophageal ph Monitoring in Children: Comparison Between Days 1 and 2.

Aim: Comparison of days 1 and 2 to each other and to the total recording of 48 hours in continuous 48-hour wireless esophageal pH monitoring in children. Methods: A retrospective study of 105 patients who underwent 48-hour pH monitoring (Bravo) studies between January 1992 and June 2010 was performed. Reflux variables were compared between days 1 and 2. Results: A total of 58 (55.2%) patients were men. The number of reflux episodes, number of long reflux >5 minutes, duration of the longest reflux (minutes), time pH <4 (minutes), fraction time pH <4 supine (%), fraction time pH <4 upright (%), reflux index, and DeMeester score did not differ between days 1 and 2. Conclusions: No effect of anesthesia was observed on the gastroesophageal reflux parameters on children.