Eric Hassall

Mechanisms of gastroesophageal reflux and gastroesophageal reflux disease.

Gastroesophageal reflux is a physiological phenomenon, occurring with different severity and duration in different individuals. Reflux occurs when this normal event results in the occurrence of symptoms/signs or complications. The pathophysiology of gastroesophageal reflux is complex and diverse, since it is influenced by factors that are genetic, environmental (e.g., diet smoking), anatomic, hormonal, and neurogenic. However, many mechanisms remain incompletely understood. Future research should focus on a better understanding of the physiology of the upper and lower esophageal sphincters, and of gastric motility. The afferent and efferent neural pathways and neuropharmacologic mediators of transient lower esophageal sphincter relaxations and gastric dysmotility require further study. The role of anatomic malformations such as hiatal hernia in children has been underestimated. While therapeutic possibilities are greater in number and largely improved, the outcomes of some treatments are far from satisfactory in many cases. In addition to development of new forms of treatment, research should address better use of currently available medical and surgical treatments.

Canadian Helicobacter Study Group Consensus Conference on the Approach to Helicobacter Pylori Infection in Children and Adolescents

Gastric infection with Helicobacter pylori is common in both children and adults, but children are considerably less susceptible to peptic ulcers and other pathological sequelae. As a result, the risk to benefit ratio of diagnostic studies and therapeutic regimens for H pylori in adults are likely different from those in pediatric populations. These guidelines for the management of pediatric H pylori infection, developed by the Canadian Helicobacter Study Group, are designed to identify when the diagnosis and treatment of H pylori may improve patient care. Given the low prevalence of this infection in Canada, it is important to recognize that indiscriminate testing and treatment programs in children are not recommended, and indeed may threaten the optimal care of children. Diagnostic tests should be employed judiciously and be reserved for children who are most likely to derive measurable benefit, such as those likely to have peptic ulcer disease. At this time a test and treat strategy in children cannot be considered prudent, evidence based or cost effective. It is appropriate to limit diagnosis and treatment to children and adolescents in whom H pylori has been identified during endoscopic investigation.

Barrett's esophagus : new definitions and approaches in children

BE is a disorder that occurs in children likely as a consequence of prolonged GE reflux of gastroduodenal contents. It usually presents with complications of GE reflux, but it also may be relatively silent in childhood and then present with adenocarcinoma in childhood or present in adulthood. Although seldom recognized in children until relatively recently, it is being diagnosed with greater frequency but not always accurately. The diagnosis of BE can be made with certainty only if landmarks are carefully documented, and a detailed histologic map is made from multiple, large biopsies taken under direct vision at endoscopy; the diagnosis should be reserved for those patients where Barretts specialized epithelium i.e., goblet cell metaplasia, is present. BE is a diagnosis that should be made with thorough documentation because of the implications for regression, cancer, and the need for follow-up and endoscopic biopsy surveillance. For treatment of complications and because there may be a chance for regression of a young (i.e., childhood) lesion, antireflux surgery or indefinite aggressive acid suppressing medical therapy is required. Because bile reflux may have a pathogenic role in BE, and because of the proven benefits of surgery in producing partial regression and prevention of dysphagia and cancer in some patients, the authors preference at present is for surgery. For children who are poor candidates for surgery, long-term omeprazole should be used (159). Adenocarcinoma does occur in childhood as a complication of BE. Because it can be recognized early, regular surveillance of children with bona fide BE is advisable.

Olsalazine Versus Sulfasalazine in Mild to Moderate Childhood Ulcerative Colitis: Results of the Pediatric Gastroenterology Collaborative Research Group Clinical Trial

The safety and efficacy of olsalazine sodium was compared to sulfasalazine over 3 months in a multicenter, randomized, double-blind study of 56 children with mild to moderate ulcerative colitis. Twenty-eight children received 30 mg/kg/day of olsalazine (maximum, 2 g/day) and 28 received 60 mg/kg/day of sulfasalazine (maximum, 4 g/day). Side effects were frequent in both groups. Eleven of 28 patients (39%) on olsalazine reported headache, nausea, vomiting, rash, pruritus, increased diarrhea, and/or fever. Thirteen of 28 on sulfasalazine (46%) reported similar side effects and/or neutropenia, and four patients had the drug stopped because of an adverse reaction. After 3 months, 11 of 28 (39%) on olsalazine were asymptomatic or clinically improved, compared to 22 of 28 (79%) on sulfasalazine (p = 0.006). In addition, 10 of 28 patients on olsalazine versus one on sulfasalazine required prednisone because of lack of response or worsening of colitis (p = 0.005). The dose of olsalazine used in this clinical trial was thought to be equivalent to a standard dose of sulfasalazine, but fewer patients on olsalazine improved and a greater number had progression of symptoms when compared to sulfasalazine. Although side effects were slightly less frequent for olsalazine, the number of patients was too small to detect a clinically significant difference.

Over-Prescription of Acid-Suppressing Medications in Infants: How It Came About, Why It’s Wrong, and What to Do About It

It has been almost 20 years since proton pump inhibitors (PPIs) were initially shown to be effective, safe, and well-tolerated for the short-term treatment of gastroesophageal reflux disease (GERD) in children over 1 year of age 1 ; GERD diagnosed on the basis of symptoms and hard diagnostic evidence of erosive esophagitis seen at endoscopy. 2 In these studies, mostly performed in children 2 to 17 years of age, 1-3 PPIs were shown to effectively treat symptoms and erosive esophagitis that were refractory to histamine-2receptor antagonists (H2RA), buffering agents, prokinetics, and in some subjects, antireflux surgery. Subsequent to those studies with omeprazole, other PPIs were found to be similarly effective. 4-8 Efficacy and safety were also shown for maintenance of remission of chronic, relapsing erosive esophagitis in prospective studies as long as 2 years, 9 and retrospective studies as long as 11 years of use. 10 Approximately 80% 10 of children who require long-term treatment for GERD have underlying disorders that predispose them to GERD, such as neurologic impairment, repaired congenital esophageal anomalies (eg, esophageal atresia), chronic lung disease, hiatal hernia, a strong family history of GERD, Barrett’s esophagus, or esophageal adenocarcinoma, or obesity. 11 In children without these underlying disorders, GERDisusuallynotchronicorsevere, 12 andmostcommonly follows a presumed upper gastrointestinal infection with post-infectious dysmotility and delayed gastric emptying, which resolves with time. In other words, in most otherwise healthy children, GERD is not chronic. In children in whom it is, the use of PPIs has revolutionized the long-term treatment of GERD, much for the better, including allowing for significantly decreased rates of antireflux surgery in some centers. 13 In this overall context, the topic of reflux in infants (ie, 7-fold increase in PPI prescription. One of the PPIs, available in a child-friendly liquid formulation, saw a 16-fold increase in use during that 6-year period. 14 Overall, approximately 0.5% of the approximately one million infants in the study database received a PPI during their first year of life. Approximately 50% of the infants started taking a PPI before 4 months of age. 15 These data would imply that somehow the diagnosis of GERD has been missed over the past several decades or has recently become a major scourge of infants in the developed world, with acid suppressing drugs becoming a new essential food group in their own right. This change in practice has come about for several reasons, none based in medical science. There is, however, data to show that this practice does not serve our patients. Two phenomena have long been observed in otherwise healthy, thriving infants. First, many of them spit up on a daily basis—some 40% to 70%. 16,17 The developing, rapidly-growing infant takes in feeding volumes that on a per-kg basis are huge compared with older children or adults. Infants have relatively poor gastric compliance and a short esophagus; therefore, some of the large volume intake simply overflows upward, or sometimes ‘‘spills’’ (lingua Australiana) out through the mouth. This has long been recognized as physiologic reflux not reflux disease [ie, not GERD]), and it is self-resolving in approximately 95% of

Successful pancolonoscopy and ileoscopy in children

Summary: The purpose of this study was to collect prospective data regarding the quality, extent, and duration of pediatric pancolonoscopy performed by pediatric gastroenterology attending physicians and a fellow in training. Over 7 months, data were prospectively collected on 40 colonoscopic procedures. The cecum was reached in 37 cases (92.5%) and the terminal ileum in 35 cases (87.5%). When cases of stricture and equipment failure were excluded, these completion rates were 97 and 95%, respectively. The overall average duration for pancolonoscopy, ileoscopy, multiple biopsies, and polypectomy (where necessary) was 38 min. When attending physicians performed the procedure, the duration was 31 min; the duration was 37 min when the fellow completed the procedure and 45 min when the fellow required the attending physician to complete it. The average time taken to reach the cecum by the attending physician was 19 min (range, 8–32); by the fellow it was 25 min (range, 17–32), and by the combination it was 37 min (range, 11–59). The average time from cecum to terminal ileum was 3 min for all, with ranges of 1–12 min for the attending physician and 1–23 min for the fellow. The fellow initiated 24 procedures, of which the attending physician was required to complete 12, including all five procedures performed in the initial 2 months of the study, 7 of 13 in the next 3 months, and none of the six procedures in the last 2 months. Of the 40 examinations, the colon was normal in five (12.5%), and a specific diagnosis was made in 35. There were no complications due to the procedure itself, but two patients had mild self-limited adverse effects from the sedation. No child had any recall of the procedure. Pancolonoscopy with ileoscopy in children is sensitive and specific for diagnosis. It is well-tolerated by children when adequate sedation with close monitoring is used; it is safe when performed by experienced pediatric gastroenterologists or a fellow in training under close supervision. Trainees can acquire the skills necessary to perform this challenging procedure in children when they are closely supervised and guided in a dedicated pediatric gastroenterology program.

safety of Lansoprazole in the Treatment of Gastroesophageal Reflux Disease in Children

Objectives: To evaluate the safety of lansoprazole in children between 1 and 11 years of age. Methods: In a phase I/II, open‐label, multicenter (11 sites) study, children with symptomatic gastroesophageal reflux disease (GERD), erosive esophagitis (≥grade 2), and/or esophageal pH < 4 for > 4.2% of the 24‐hour period were assigned, on the basis of body weight, to lansoprazole 15 mg (≤30 kg) or 30 mg (>30 kg) once daily for 8 to 12 weeks. At the discretion of the investigator, the dosage of lansoprazole was increased up to 60 mg daily in children who continued to be symptomatic after 2 weeks of treatment. Safety for all study participants was monitored by adverse event reports and laboratory evaluations. Results: Sixty‐six children were enrolled in the study and were included in the safety analysis. Throughout the treatment period, no child discontinued therapy because of an adverse event and no. clinically significant changes in laboratory values were observed. Three of the 32 children (9%) who received lansoprazole 15 mg once daily (mean exposure 50.3 days) and 6 of the 34 children (18%) who received the 30 mg once‐daily dose (mean exposure 49.4 days) experienced one or more treatment‐related adverse events before any dose increase. The three children in the lansoprazole 15 mg treatment group were treated with doses of 0.6 mg to 1.2 mg/kg/day; those in the lansoprazole 30 mg treatment group were treated with doses of 0.7 mg to 0.9 mg/kg/day. Only one child experienced a new treatment‐related adverse event after an increase in lansoprazole dose to 1.3 mg/kg/day. Treatment‐related events experienced by two or more children were: constipation (lansoprazole 15 mg QD, two children; lansoprazole 30 mg QD, one child), and headache (lansoprazole 30 mg QD, two children). Mean fasting serum gastrin levels were significantly increased from 58.0 pg/mL at baseline to 112.4 pg/mL at week 2 and 121.9 pg/mL at the final visit (P ≤ 0.001 for each comparison). However, the median fasting serum gastrin levels at the week 2 and the final visit were within the normal range (25‐111 pg/mL). Conclusion: Lansoprazole, when administered on the basis of body weight in children between 1 and 11 years of age, is safe and well‐tolerated.

Antireflux Surgery in Children: Time for a Harder Look

* Abbreviations:n ARS = : antireflux surgery • NI = : neurologic impairment • GER = : gastroesophageal reflux • PPIs = : proton pump inhibitorsnnAntireflux surgery (ARS) is said to be the most common operation performed by pediatric surgeons, excluding minor procedures such as inguinal herniorrhaphy and central line placement. In recent years, pediatric surgeons and others have documented high rates of failure and morbidity of ARS and occasional mortality.1-10 These problems occur especially in children with neurologic impairment (NI), or repaired esophageal atresia, or chronic lung disease, and to a lesser degree in otherwise normal children.10 For example, in one study, compared with neurologically normal children, NI children had more than twice the complication rate, three times the morbidity rate, and four times the reoperation rate of ARS, within a mean follow-up of only 1.6 years.1 In another study,2 >30% of NI children had major complications or died within 30 days of surgery; within a mean follow-up of 3.5 years, 25% had documented operative failure, and overall 71% had return of one or more preoperative symptoms of gastroesophageal reflux (GER). Some surgeons have concluded that, in NI children, “The use of fundoplication to … improve outcome with an acceptably … nnAddress correspondence to: Eric Hassall, MBChB, FRCP(C), Division of Gastroenterology, British Columbia Childrens Hospital, 4480 Oak St, Vancouver, British Columbia, V6H 3V4 Canada.

Partial splenic embolization in children with hypersplenism

As an alternative to surgical splenectomy, partial splenic embolization was performed in seven children for hypersplenism manifested by splenomegaly, thrombocytopenia, leukopenia, and erythrocyte hemolysis. Within a few days, platelet and leukocyte counts rose significantly in all patients and were maintained in six of seven patients during a follow-up period of 9 to 69 months. Spleen size and abdominal distention also decreased significantly in all children. There were no infectious complications.

Development and psychometric evaluation of 2 age-stratified versions of the Pediatric GERD Symptom and Quality of Life Questionnaire.

Objectives:The Pediatric Gastroesophageal Reflux Disease Symptom and Quality of Life Questionnaire (PGSQ) represents 2 related age-stratified tools developed to assess pediatric gastroesophageal reflux disease (GERD). These include the PGSQ-Cp (for children ages 2 to 8 years, parent/caregiver report) and the PGSQ-A (for adolescents ages 9–17 years). The objective of the present study was to develop and evaluate PGSQ measurement properties. Materials and Methods:The PGSQ items were generated based on information from focus groups, expert clinician review, and cognitive debriefing interviews. The symptoms of pediatric GERD and the effect of these symptoms were addressed. The tools were evaluated in a 3-week psychometric evaluation with participants from 11 clinical sites in the United States. The study included other measures such as the Pediatric Quality of Life questionnaire (PedsQL) and clinician-rated GERD severity. After item reduction, internal consistency, reproducibility, construct validity, known-group validity, and responsiveness were assessed. Results:The 231 participants included 75 parents of children ages 2 to 8 years and 75 children ages 9 to 17 years with GERD and 41 parents of children and 40 children ages 9 to 17 years without GERD. Exploratory factor analysis demonstrated 4 symptom subscales for the PGSQ-Cp and 3 symptom subscales for the PGSQ-A. Both had subscales for total impact and school impact. High to moderate internal consistency was observed, ranging from 0.76 to 0.96 for the PGSQ-Cp and from 0.67 to 0.94 for the PGSQ-A. The PGSQ significantly differentiated between patients with GERD and controls (P < 0.0001, PGSQ-Cp; P < 0.0022–0.0001, PGSQ-A) and demonstrated responsiveness. Conclusions:These results support the reliability, validity, and responsiveness of both versions of the PGSQ. The instruments should be useful for clinical studies.