Persistent Reflux Symptoms Research Articles

Gangliocytic Paraganglioma of the Ampulla of Vater: Case Series and a Systematic Review

Purpose: To define the effectiveness of endoscopic approach for gangliocytic paraganglioma (GP) of the ampulla of Vater. Methods: Two reviewers independently conducted a detailed literature search on major electronic databases including PubMed, Ovid Medline, Cochrane Library, and Embase using MeSH terms: gangliocytic paraganglioma, neuroendocrine tumor, periampullary and duodenal neoplasm. The reference list of each article was then hand-searched. Exclusion criteria are incomplete clinical data and lack of histology. We also identified two cases from our institution. Results: A total of 42 studies were scanned. We identified 28 studies (31 patients, 11 female, 20 male) with the mean age of 53 years (interquartile range 43-60), published between 1980 and 2012, to characterize natural history and response to treatments. In our series, a 54-year-old male and a 47-year-old male presented with persistent gastroesophageal reflux symptoms requiring upper endoscopy, which revealed a 20 mm and a 15 mm ampullary mass, respectively. Endoscopic ultrasonography (EUS), computer tomography (CT), and magnetic resonance imaging (MRI) showed no invasion or metastasis. Endoscopic ampullectomy was performed in both patients. In our systematic review, presenting symptoms included abdominal pain in 33%, jaundice in 24%, gastrointestinal bleeding in 18%, weight loss in 3%, and pancreatitis in 3%. Interestingly, neurofibromatosis was found in four patients. Treatments included pancreaticoduodenectomy in 21 patients, transduodenal laparoscopic ampullectomy in five patients, and endoscopic ampullectomy via endoscopic retrograde cholangiopancreaticography (ERCP) in seven patients (including our series). All patients who underwent endoscopic approach had a tumor size of less than 20 mm, and no evidence of tumor invasion or metastasis on EUS, CT, and MRI. The mean of tumor size was 20 mm (16-37). Among 33 patients, there were four patients with regional lymph node metastasis. The mean of follow up was 13 months (12-24), revealing no recurrence. Conclusion: The majority of ampullary GP has a benign course and excellent response to excision. Our series and recent studies showed that endoscopic resection of the tumor is feasible in selected patients, with reassuring results on comprehensive evaluations, including EUS, with evidence of submucosal confi nement, tumor size of less than 20 mm, and CT and MRI without evidence of metastasis, to avoid unnecessary major operation such as pancreaticoduodenectomy and its complications.

Systematic review: the association between symptomatic response to proton pump inhibitors and health-related quality of life in patients with gastro-oesophageal reflux disease

Some patients with gastro-oesophageal reflux disease (GERD) experience persistent reflux symptoms on proton pump inhibitor (PPI) therapy. The relationship between persistent reflux symptoms and health-related quality of life (HRQoL) is unclear. To assess the relationship between persistent reflux symptoms on PPI therapy and HRQoL in patients with GERD. Systematic searches were conducted in PubMed and Embase. Eligible studies had to have used psychometrically evaluated patient reported outcome instruments to assess HRQoL. Nine studies were included; supplementary data were obtained for four of these. The effect of persistent reflux symptoms despite PPI therapy on physical HRQoL was assessed in seven studies and that on mental HRQoL in five studies. Compared with patients whose reflux symptoms responded to PPIs, those with persistent symptoms had, on average, 8-16% lower scores for physical health (five studies) and 2-12% lower scores for mental health (three studies). Three studies included data on the effect of baseline HRQoL on subsequent symptomatic response to PPI therapy. Patients with persistent symptoms had clinically relevant lower psychological well-being at baseline compared with those whose symptoms responded to PPIs (average score difference: 7%; two studies). High anxiety levels at baseline seemed to be an important aspect of persistent symptoms. Persistent reflux symptoms on PPI therapy are associated with reduced physical and mental HRQoL, while reduced mental HRQoL at baseline seems to impair symptomatic response to PPIs. HRQoL may need to be considered alongside reflux symptom frequency and severity when making decisions about disease management.

Assessment of Functional Esophageal Mucosal Integrity in Biopsies of Patients With Refractory NERD

Introduction Patients with non-erosive reflux disease (NERD) exhibit oesophageal mucosal epithelial dilated intercellular spaces (DIS), which can be reversed by PPI therapy and are not seen in patients with functional heartburn. Oesophageal mucosal functional integrity can be evaluated by measuring transepithelial electrical resistance (TER) and permeability to small molecules. Such functional changes may be relevant for symptom perception but are thus far not studied in NERD. We investigated oesophageal mucosal functional integrity in patients with GORD symptoms refractory to PPI. Methods Oesophageal biopsies at 3 cm above the squamo-columnar junction were obtained from 17 patients with persistent typical reflux symptoms (heartburn, regurgitation) on PPI but with no erosions (mean age 52, range 35–76), and 10 control subjects (no upper GI symptoms; mean age 38, range 18–54). Biopsies were placed in micro-Ussing chambers and baseline TER measured after equilibration in KHBB pH 7.4 solution. The mucosal side of the biopsies was then exposed for 30 min to either: KHBB control solution at pH 7.4; weakly acidic solution pH 5 + 1 mg/ml pepsin + 1 mM sodium deoxycholic acid; or acidic solution pH 2 + 1 mg/ml pepsin + 1 mM taurodeoxycholic acid. % change in TER at the end of the exposure was recorded. Following this the mucosal chamber solution was replaced with KHBB pH 7.4 + 1 mg/ml fluorescein. Passage of fluorescein to the serosal chamber was measured after 2 h. Results There was no significant difference between controls and NERD patients on PPI with regards to TER baseline (74±6 Ω/cm 2 vs 99±11 Ω/cm 2 ) or permeability after exposure to the pH 7.4 solution. There was no reduction in TER after 30 min exposure to the pH 7.4 solution. Exposure to acidic solution resulted in a significant reduction in TER (−25.0±2.9%, p Conclusion In basal conditions or after exposure to aggressive acidic solutions, oesophageal mucosal integrity of NERD patients refractory to PPI did not differ from controls. However, mucosal exposure to weakly acidic + bile acid solutions produced a distinct response in these patients, suggesting an increased susceptibility which may explain some patients9 apparent hypersensitivity to weakly acidic refluxate and failure of PPI therapy.

Persistent dual high pressure zone, oesophageal body hypomotility and abnormal response to multiple rapid swallows are associated with reflux symptoms after fundoplication

IntroductionPersistent reflux symptoms occur in a subgroup of patients following antireflux surgery. These symptoms can be due failure of the antireflux barrier. GI physiology studies are performed to evaluate the...

Assessment of functional oesophageal mucosal integrity in biopsies of patients with refractory gord

IntroductionPatients with non-erosive reflux disease (NERD) exhibit oesophageal mucosal epithelial dilated intercellular spaces (DIS), which can be reversed by PPI therapy and are not seen in patients with functional heartburn....

A novel reflux inhibitor lesogaberan (AZD3355) as add-on treatment in patients with GORD with persistent reflux symptoms despite proton pump inhibitor therapy: a randomised placebo-controlled trial

ObjectiveTo evaluate the efficacy and tolerability of add-on treatment with lesogaberan (AZD3355), a novel reflux inhibitor, in patients with persistent gastro-oesophageal reflux disease (GORD) symptoms despite proton pump inhibitor (PPI)...

Impact of prolonged 48-h wireless capsule esophageal pH monitoring on diagnosis of gastroesophageal reflux disease and evaluation of the relationship between symptoms and reflux episodes

Gastroesophageal reflux disease is one of the most common digestive diseases and an important cause of distress to patients. Diagnosis of this condition can require ambulatory pH monitoring. To determine the diagnostic yield of a wireless ambulatory pH monitoring system of 48-hours, recording to diagnose daily variability of abnormal esophageal acid exposure and its symptom association. A total of 100 consecutive patients with persistent reflux symptoms underwent wireless pH capsule placement from 2004 to 2009. The wireless pH capsule was deployed 5 cm proximal to the squamocolumnar junction after lower esophageal sphincter was manometrically determined. The pH recordings over 48-h were obtained after uploading data to a computer from the receiver that recorded pH signals from the wireless pH capsule. The following parameters were analyzed: (1) percentual time of distal esophageal acid exposure; (2) symptom association probability related to acid reflux. The results between the first and the second day were compared, and the diagnostic yield reached when the second day monitoring was included. Successful pH data over 48-h was obtained in 95% of patients. Nearly one quarter of patients experienced symptoms ranging from a foreign body sensation to chest pain. Forty-eight hours pH data analysis was statistically significant when compared to isolated analysis of day 1 and day 2. Study on day 2 identified seven patients (30.4%) that would be missed if only day 1 was analyzed. Three patients (18.7%) out of 16 patients with normal esophageal acid exposure on both days, showed positive symptom association probability, which generated an increase in diagnostic yield of 43.4%. Esophageal pH monitoring with wireless capsule is safe, well tolerated, does not require sedation. The extended 48-h period of study poses an increased yield to diagnose gastroesophageal reflux disease patients.

Effects of anti-reflux surgery on weakly acidic reflux and belching

BackgroundLaparoscopic Nissen fundoplication (LNF) is the most frequently performed operation for gastro-oesophageal reflux disease (GORD). However, 12% of the patients have persistent reflux symptoms and 19% develop gas-related symptoms after...

Primary Lymphoma of the Esophagus: A Rare Cause of Rapid Dysphagia

Purpose: To increase awareness of primary esophageal lymphoma and its characteristic clinical, endoscopic, and histological manifestations. Results: A 71-year-old woman with history of Waldenstrom's macroglobulinemia and hypothyroidism presented with heartburn. Physical examination was within normal limits including absent palpable superficial lymphadenopathy. An upper endoscopy performed at that time revealed normal esophageal and gastric mucosa. Colonoscopy was also normal. Patient was placed on protonpump inhibitor (PPI) therapy for non-erosive reflux disease. Despite maximal PPI therapy, patient continued to complain of reflux symptoms and developed dysphagia and odynophagia. She was only able to tolerate soft, bland foods, and often experienced regurgitation within seconds of eating. She endorsed a 10lb weight loss over 8-12 weeks. A barium swallow performed 10 weeks after initial evaluation revealed irregular narrowing in the distal esophagus. Repeat endoscopy showed a firm, friable, ulcerated mass with overlying exudate between 34 and 38 cm from the incisors. At 38 cm from the incisors, stricturing was encountered through which a standard 9.8 mm endoscope could not pass. A 5.9mm stricture scope was able to traverse this area and revealed 2cm of normal-appearing esophageal mucosa and a well-appearing Z-line. Multiple cold forceps biopsies were taken of the mass. Pathology revealed diffuse large B-cell lymphoma of the non-germinal center type. EBV staining was negative. The patient was treated with a combination of Rituximab plus cyclophosphamide, vincristine, adriablastin, and prednisone (RCHOP) and a rapid treatment response was noted. Isolated primary lymphoma of the esophagus is an extremely rare diagnosis, with fewer than 25-30 cases reported in the literature. A non-mucosal origin to the tumor likely explains the normal initial endoscopy in our patient. Conclusion: Primary esophageal lymphoma is an extremely rare cause of rapid dysphagia and should be considered in the differential diagnosis of esophageal neoplasms. Persistent reflux symptoms despite maximal PPI therapy and the emergence of alarm symptoms (dysphagia, weight loss, anemia) warrant immediate investigation.

Systematic review: persistent reflux symptoms on proton pump inhibitor therapy in primary care and community studies

Persistent gastro-oesophageal reflux disease (GERD) symptoms can occur despite proton pump inhibitor (PPI) therapy. To assess the prevalence and potential determinants of persistent GERD symptoms in primary care and community-based studies. Studies were identified by systematic PubMed and Embase searches; pooled prevalence data are shown as sample-size weighted means and 95% confidence intervals. Nineteen studies in individuals with GERD taking a PPI were included. In interventional, nonrandomized primary care trials, the prevalence of persistent troublesome heartburn and regurgitation was 17% (6-28%) and 28% (26-30%) respectively; in randomized trials, it was 32% (25-39%) and 28% (26-30%), respectively. In observational primary care and community-based studies, 45% (30-60%) of participants reported persistent GERD symptoms. Overall, persistent GERD symptoms despite PPI treatment were more likely in studies with a higher proportion of female participants [>60% vs. <50%, risk ratio (RR): 3.66; P < 0.001], but less likely in studies from Europe than in those from the USA (RR: 0.71; P < 0.001), and were associated with decreased psychological and physical well-being. Persistent GERD symptoms despite PPI treatment are common in the primary care and community setting. Alternative approaches to management are required.

T1680 Functional Heartburn Patients are Characterized by Increased Frequency and Perception of Liquid-Gas and Proximal Reflux

s / Digestive and Liver Disease 42S (2010) S61–S192 S105 can increase gastrin levels. More recently also CgA concentrations have been found elevated during PPI therapy. A possible use of this parameter in evaluating ECL hyperplasia, within this context, has been suggested. This study was undertaken to investigate the relationship between gastrin and CgA levels and intragastric pH during acid suppressive therapy to evaluate the behaviour of serum gastrin and CgA in patients under prolonged PPI treatment. Material and methods: 24-hour gastric-oesophageal pH-metry was performed in 25 patients with persistent reflux symptoms after at least 3 months of PPI treatment. Blood samples for gastrin and CgA were collected before starting the procedure and assessed by radioimmunoassay. Gastrin and CgA were also evaluated in 50 patients under long term PPI therapy (more than 1 year) for GERD. Repeated measurements on/off therapy were available in 10 cases. Results: Increased gastrin and CgA values were found in 13 (58%) and in 19 (76%) patients undergoing ph-metry respectively. 6 patients with elevated CgA displayed normal gastrin levels. No correlation was evidentiated between G (r= 0.24; p=0.25) and CgA (r= 0.102; p=0.63) concentrations and the degree of inhibition of gastric secretion expressed as % of time with gastric pH over 4 during 24-hour. In patients on long term treatment, elevated G and CgA levels were detected in 34 (68%) and 39 (78%) cases respectively (range 132-1000 pg/ml for G and 122-1250 ng/ml for CgA). Within patients with hypergastrinemia 4 presented normal CgA; within those with increased CgA 9 had normal gastrin. In this latter group PPI withdrawal, when performed, resulted in CgA normalization; furthermore, of the 3 patients who underwent endoscopy, 2 showed ECL hyperplasia at histology. Conclusions: According to our data, serum gastrin and CgA concentrations during PPI therapy are highly variable within patients and not related to the degree of suppression of gastric secretion. Serum CgA seems to pick up better than gastrin patients at higher risk of ECL hyperplasia during prolonged PPI treatment. # A. Oesophagus 1. GERD

To Bravo or not? A comparison of wireless esophageal pH monitoring and conventional pH catheter to evaluate non‐erosive gastroesophageal reflux disease in a multiracial Asian cohort

Non-erosive reflux disease (NERD) constitutes the majority of patients with gastroesophageal reflux disease (GERD). Esophageal pH monitoring is useful in distinguishing patients with NERD from functional heartburn. The gastroenterologist often faces the dilemma of choosing the most appropriate investigative modality. The wireless Bravo capsule allows prolonged 48 hour monitoring with improved patient tolerance, but concerns regarding its reduced sensitivity compared to conventional pH catheter have been raised. We compared the prevalence of high esophageal acid exposure and positive symptom correlation profiles (using the symptom index [SI] and symptom association probability [SAP]) in patients who underwent Bravo compared to patients who underwent conventional pH catheter, and evaluated the efficacy of Bravo monitoring in a multiracial Asian cohort. Retrospective analysis of all pH studies performed between January 2004 and February 2009 for patients with persistent reflux symptoms and a normal gastroscopy. 66 (27 Male, 42.4 +/- 13.4 years) and 55 (24 Male, 47.1 +/- 13.3 years) patients underwent wireless and pH catheter evaluation respectively. "True NERD" (abnormal acid exposure) was diagnosed in 26 (39.4%) and 20 (36.4%) patients (pNS) while "acid-sensitive esophagus" (SI > or = 50% and/or SAP > or = 95%) occurred in 14 (21.2%) and 12 (21.8%) patients (pNS) using the wireless and pH catheter respectively. Extended recording time with Bravo led to an incremental diagnostic yield of 30%. The wireless capsule was well tolerated. The diagnostic yield was similar using both modalities. With the increasing availability of impedance-pH technology, it is uncertain if devices that detect only acid-reflux events will be surpassed.

Persistent symptoms on therapy—test on therapy

When all state-of-the-art reflux monitoring technologies are available, which should be used for patients who have persistent reflux symptoms despite acid suppressive therapy? A single-center study has investigated this clinical dilemma and provides guidance on the best diagnostic strategy.

Acid and non-acid reflux in Japanese patients with non-erosive reflux disease with persistent reflux symptoms, despite taking a double-dose of proton pump inhibitor: a study using combined pH-impedance monitoring

Combined multi-channel intra-luminal impedance and pH (Mll-pH) monitoring can detect gastro-esophageal reflux and identify acid and non-acid reflux (NAR) events. It can be used for patients with persistent symptoms who are having proton pump inhibitor (PPI) therapy. The aim of this study is to determine the frequency of acid reflux and NAR and to establish their relationship with persistent reflux symptoms in Japanese patients with non-erosive reflux disease (NERD) who are on a double-dose of PPI therapy. Thirteen patients with NERD, with persistent reflux symptoms, despite taking PPI at least twice daily, were included in this study. Twenty-four-hour combined Mll-pH monitoring was carried out on all patients and reflux episodes were detected by impedance channels, located at 3, 5, 7, 9, 15 and 17 cm above the lower esophageal sphincter (LES) and classified into acid reflux and NAR, based on pH data from 5 cm above the LES. A positive symptom index (SI) was declared, if at least half of the symptoms were preceded by reflux episodes within 5 min. A total of 916 liquid reflux episodes were detected, and a total of 171 symptoms were recorded. Eight (4.7%) of 171 symptoms were related to acid reflux, and 68 (39.8%) were related to NAR. Seven (53.8%) patients had a positive SI and in these seven patients, a total of 79 symptoms were recorded. 5 (6.3%) of the 79 symptoms were related to acid reflux and 44 (55.7%) were related to NAR. Persistent reflux symptoms, in SI-positive patients with NERD on double-dose PPI therapy, are more likely to be associated with primarily non-acid reflux.

Systematic review: persistence and severity in gastro‐oesophageal reflux disease

Management strategies for gastro-oesophageal reflux disease (GERD) are often inconsistent with the proposition that it is a persistent or chronic disease. To determine the persistence of reflux symptoms and complications associated with GERD. Systematic searches of Medline and EMBASE. In longitudinal studies, 65% (95% CI 54-75%) of patients with complicated GERD and 70% (95% CI 57-83%) of patients with 'defined' GERD had persistent disease at follow-up, whereas 34% (95% CI 27-40%) with infrequent or mild reflux symptoms at baseline had persistent symptoms. Clinical trials of maintenance treatment for at least 6 months after healing of oesophagitis reported mean relapse rates of 75% (95% CI 68-82%) in patients taking placebo and 28% (95% CI 21-35%) in those taking proton pump inhibitors. Retrospective studies reported that 34-41% of individuals with GERD recalled experiencing their symptoms for >10 years. The prevalence of GERD is high (10-20%), whereas the incidence is low (4.5-19.6 cases per 1000 person-years), suggesting that GERD is likely to persist for at least 18 years. Individuals with GERD have persistent reflux symptoms that merit management as a chronic disease; infrequent reflux symptoms are less likely to be chronic and may respond to different management strategies.

Use of Narrow Band Imaging (NBI) To Detect Esophagitis in Non Erosive Reflux Disease (NERD)

Purpose: Most patients with reflux symptoms do not have signs of mucosal injury on routine endoscopy. In patients with non erosive reflux disease (NERD) chromoendoscopy with Lugol's iodine and confocal laser endomicroscopy have been reported to identify lesions with histologic evidence of esophagitis. However, both procedures are time consuming and require the use of contrast agents. Narrow band imaging (NBI) is known to display macroscopic lesions such as ulcers with high contrast and clarity. We report our findings in an initial group of patients with persistent reflux symptoms and a normal esophagus on white light (WL) endoscopy to see if erosive lesions could be detected with high contrast NBI endoscopy. Methods: The Olympus GIF-H180 gastroscope was used in five patients; 3 male, 2 female, with a mean age of 49 (range 22–63) who underwent upper endoscopy for persistent reflux symptoms (heartburn at least 3 times per week for more than 3 months). On finding no evidence of esophagitis on WL endoscopy in all 5 patients, the NBI mode was switched on and the esophagus re-examined. Any discrete lesions were photographed and biopsies taken with cold forceps for histology. If no lesions were seen, biopsies were taken from the distal esophagus. Results: In asymptomatic individuals, NBI displays the normal esophagus with an even blue color. On switching to narrow band imaging (NBI) mucosal breaks or erosions were seen in 4 out of 5 patients (80%). These consisted of: 1) discrete, depressed erosions of up to 1 mm in diameter, surrounded by an even, bluish appearing normal squamous mucosa; 2) larger, flat, depressed, magenta colored patches of up to 10 mm in diameter, with visible raised margins. Targeted biopsies from these lesions showed microscopic evidence of reflux esophagitis in all 4 patients (100%). Biopsies from the distal esophagus of the patient without mucosal lesions were normal. Conclusion: These early findings suggest that high contrast imaging methods such as NBI may be useful in unmasking subtle erosive changes in the esophagus of patients with reflux symptoms that are not readily visible on routine white light endoscopy. High contrast imaging with NBI is a rapid and easy technique that does not require complex instrumentation or dyes. If these initial findings are verified by future studies, this may become a useful technique for identifying erosive lesions and targeting biopsies in patients with presumed NERD.

Review article: complete gastro‐oesophageal reflux monitoring – combined pH and impedance

Gastroesophagel reflux disease (GERD) is a common condition encountered in clinical practice. Over the years there has been a continuous interaction between the understanding of the disease, the diagnostic tools and treatments of GERD. The use of proton pump inhibitor (PPI) trials by primary care physicians as diagnostic tool in patients with symptoms suspected to be due to GERD has led to a shift in the type of patients referred to specialists. Currently, gastrointestinal specialists are frequently asked to evaluate patients with persistent reflux symptoms despite acid suppressive therapy. In these patients symptoms can be associated with reflux (both acid and non-acid) or not associated with reflux. While conventional pH monitoring can quantify esophageal acid exposure and evaluate the association between symptoms and acid reflux, it cannot reliably detect reflux episodes with a pH > 4 (i.e. non-acid reflux). Detecting reflux episodes by changes in intraluminal resistance to alternating current (i.e. impedance), combined multichannel intraluminal impedance and pH (MII-pH) monitoring offers the opportunity to detect both acid and non-acid reflux episodes and to evaluate the relationship between symptoms and reflux. We believe that MII-pH monitoring has become the new ''gold standard'' for clarifying the mechanisms of persistent symptom on PPI therapy.

A 22 year old man with persistent regurgitation and vomiting: case progression

Last week ( BMJ 2006;332:) we presented the case of Mr Neville, a 22 year old student with persistent severe epigastric pain and regurgitation and vomiting after meals. Investigation suggested...

Oral ranitidine and duration of gastric pH &gt;4.0 in infants with persisting reflux symptoms

Abstract Background: Ranitidine is a drug commonly used in pathological gastro‐oesophageal reflux (GOR) in infants. Non‐responsiveness has been reported. Data regarding the effect of ranitidine on oesophageal acid exposure and reduction of gastric acid secretion are limited in this age group. Objective: To evaluate oesophageal acid exposure, reduction of gastric acid secretion and histology of oesophageal biopsies in infants who clinically do not respond to oral ranitidine. Patients and design: 103 infants (mean age 3.3±1.8 mo) with persisting symptoms of reflux despite administration of ranitidine, prescribed previously by a referring physician, at a mean (SD) dose of 9.4 (±3.3) mg/kg/d for at least 2 wk (mean 30 d), were submitted to a 24‐h pH study and oesophageal biopsy (90/103 patients). Results: Histological oesophagitis was present in 21/90 (23%). The oesophageal reflux index (RI) was &gt;5% and &gt;10% in 21/103 (20%) and 6/103 (6%) infants, respectively. Gastric pH was &gt;4.0 during &lt;50%, &gt;50%, &gt;75% and &gt;90% of the duration of pH monitoring in 33/103 (32%), 70/103 (68%), 22/103 (21%) and 7/103 (7%), respectively. By simple regression analysis, the dosage of ranitidine correlated with the oesophageal RI (r=0.21; p=0.05), but not with the duration of time gastric pH was &gt;4.0 (r=0.09; p=0.39). Histological oesophagitis did not correlate with ranitidine dosage, duration of treatment, duration gastric pH was &gt;4.0 and oesophageal reflux index. Conclusion: Some infants presenting with symptoms assumed to be GOR and acid related fail to respond to acid suppression with ranitidine, either because they need better acid suppression or because the symptoms are not acid related.

Oral ranitidine and duration of gastric pH &gt;4.0 in infants with persisting reflux symptoms

Ranitidine is a drug commonly used in pathological gastro-oesophageal reflux (GOR) in infants. Non-responsiveness has been reported. Data regarding the effect of ranitidine on oesophageal acid exposure and reduction of gastric acid secretion are limited in this age group. To evaluate oesophageal acid exposure, reduction of gastric acid secretion and histology of oesophageal biopsies in infants who clinically do not respond to oral ranitidine. 103 infants (mean age 3.3 +/- 1.8 mo) with persisting symptoms of reflux despite administration of ranitidine, prescribed previously by a referring physician, at a mean (SD) dose of 9.4 (+/- 3.3) mg/kg/d for at least 2 wk (mean 30 d), were submitted to a 24-h pH study and oesophageal biopsy (90/103 patients). Histological oesophagitis was present in 21/90 (23%). The oesophageal reflux index (RI) was >5% and >10% in 21/103 (20%) and 6/103 (6%) infants, respectively. Gastric pH was >4.0 during <50%, >50%, >75% and >90% of the duration of pH monitoring in 33/103 (32%), 70/103 (68%), 22/103 (21%) and 7/103 (7%), respectively. By simple regression analysis, the dosage of ranitidine correlated with the oesophageal RI (r = 0.21; p = 0.05), but not with the duration of time gastric pH was >4.0 (r = 0.09; p = 0.39). Histological oesophagitis did not correlate with ranitidine dosage, duration of treatment, duration gastric pH was >4.0 and oesophageal reflux index. Some infants presenting with symptoms assumed to be GOR and acid related fail to respond to acid suppression with ranitidine, either because they need better acid suppression or because the symptoms are not acid related.