Daily Proton Pump Inhibitor Therapy Research Articles

Voice Quality Measurement as an Indicator of Efficiency of Treatment in Laryngopharyngeal Reflux Disease

Introduction Laryngopharyngeal reflux disease can alter the structural and functional integrity of the vocal fold. Objectives of the study was to determine the effect of Laryngopharyngeal Reflux Disease (LPRD) on selected Acoustic, Aerodynamic and perceptual parameters of voice and to establish its effectiveness in therapeutic outcome. Materials and Methods The number of patients enrolled for this prospective observational study was 65, all with Reflux symptom index (RSI) more than 13. Quality of life was evaluated using voice handicap index (VHI). Perceptual evaluation of voice done by Grade Roughness Breathiness Asthenia Strain score (GRBAS) followed by acoustic and aerodynamic analysis. Patients were started on a once daily proton pump inhibitor therapy for 3 months along with vocal hygiene measures and RSI, VHI and voice analysis repeated after the treatment. Results There was significant improvement in the RSI score after treatment. Percent jitter and shimmer showed significant improvement in males post treatment (p value:<0.05). Harmonic to noise ratio improved 3 months post treatment in both sexes. Improvement noted in Maximum phonation time and GRBAS score except asthenia and strain post treatment. Conclusion Measurement of voice quality can be used as an effective tool to monitor the efficiency of treatment of LPRD.

S2869 Gastric Tissue in the Duodenal Bulb: Heterotopia or Metaplasia?

INTRODUCTION: Gastric heterotopia is the presence of well-differentiated gastric glands located in a region not anatomically expected. Though often asymptomatic and found incidentally, when symptoms are present, they may be severe leading to complications such as ulceration or bleeding1,2. Gastric heterotopia (GH) has characteristic endoscopic and histologic findings, though since it was first described, it has often been incorrectly undifferentiated from gastric metaplasia. CASE DESCRIPTION/METHODS: A 54-year-old male with history of hypothyroidism and gastroesophageal reflux disease was referred for endoscopy due to persistent reflux despite daily proton pump inhibitor therapy. EGD revealed grade B esophagitis, a 2-3mm gastric body polyp and a 2cm polyp in the duodenal bulb (Figure 1). Pathology review of the stomach polyp revealed a fundic gland-type polyp. Interestingly, the duodenal polyp sample also showed gastric fundic-type mucosa, indicative of gastric heterotopia (Figure 2). DISCUSSION: Though historically described interchangeably, the distinction between gastric heterotopia and metaplasia is critical. Histologically, GH appears as well-differentiated oxyntic glands with full mucosal thickness1,3. GH is congenital, and often found incidentally as a macroscopic lesion on endoscopy4. In contrast, gastric metaplasia (GM) is an acquired microscopic lesion with incomplete gastric glands that resides in a portion of mucosal thickness coalescent with native tissue3,4. It is a reactive process due to local inflammation, often associated with duodenitis, inflammatory bowel disease, hypergastrinemia and H. pylori3-4,6. Analysis by Matsubara et al. suggested that both GM and GH may have metaplastic potential due to GNAS and KRAS mutations, identified in 55% of GM lesions and 28% of GH lesions7. The reported prevalence of GH in the duodenal bulb has varied, ranging between 0.5- 2% of the population4. In the 1970s, post-mortem studies reported incidence of 1-2%5. A 2010 analysis of 28,000 patients reported incidence of GH in 1.9%, and additionally suggested a potential correlation between GH and gastric fundic gland polyps8. Though most cases of GH and GM are benign, investigations have introduced the possibility that a fraction may have neoplastic potential. Thus, accurate identification of these lesions is essential for endoscopists and pathologists, and further studies are needed to assess if routine surveillance for those with GH or GM is indicated.Figure 1.: Polyp in the duodenal bulb seen on endoscopy.Figure 2.: Low-power photomicrograph displaying gastric fundic-type mucosa in the duodenal bulb polyp sample.

The TEMPO Trial at 5 Years: Transoral Fundoplication (TIF 2.0) Is Safe, Durable, and Cost-effective.

Background. Questions remain about the therapeutic durability of transoral incisionless fundoplication (TIF). In this study, clinical outcomes were evaluated at 5 years post-TIF 2.0. Methods. A total of 63 chronic gastroesophageal reflux disease (GERD) sufferers with troublesome symptoms refractory to proton pump inhibitor (PPI) therapy, absent or ≤2 cm hiatal hernia, and abnormal esophageal acid exposure were randomized to the TIF group or PPI group. Following the 6-month evaluation, all patients in the PPI group elected for crossover to TIF; therefore, all 63 patients underwent TIF 2.0 with EsophyX2 device. Primary outcome was elimination of daily troublesome regurgitation and atypical symptoms at the 5-year follow-up. Secondary outcomes were improvement in symptom scores, PPI use, reoperations, and patient health satisfaction. The cost-effectiveness of TIF 2.0 was also estimated. Results. Of 63 patients, 60 were available at 1 year, 52 at 3 years, and 44 at 5 years for evaluation. Troublesome regurgitation was eliminated in 88% of patients at 1 year, 90% at 3 years, and 86% at 5 years. Resolution of troublesome atypical symptoms was achieved in 82% of patients at 1 year, 88% at 3 years, and 80% at 5 years. No serious adverse events occurred. There were 3 reoperations by the end of the 5-year follow-up. At the 5-year follow-up, 34% of patients were on daily PPI therapy as compared with 100% of patients at screening. The total GERD Health-related quality-of-life score improved by decreasing from 22.2 to 6.8 at 5 years (P < .001). Conclusion. In this patient population, the TIF 2.0 procedure provided safe and sustained long-term elimination of troublesome GERD symptoms.

An Elderly Woman With an Uncommon Cause of Dysphagia

Question: A 68-year-old woman with a past medical history of asthma and vulvar lichen planus is referred to us for symptoms of dysphagia. Her dysphagia is to solids only. Symptoms started 1 year before presentation and have been progressive in nature. There was no associated odynophagia, regurgitation, unintentional weight loss, melena, or hematochezia. She has mild symptoms of gastroesophageal reflux disease that are well controlled with once daily proton pump inhibitor therapy. Her medications include daily maximum dose inhaled steroids for asthma. She has no history of smoking or alcohol abuse. On oral examination, no lesions including oral thrush were noted. Our patient underwent a barium esophagram that showed a distal esophageal stricture (Figure A, arrows). An upper endoscopy was pursued that showed significant mucosal changes with white plaques, ulcers, and scarring causing luminal narrowing and friability (Figure B–E). Multiple large unstained lesions on Lugol's chromoscopy were noted (Figures F, G). Multiple biopsies were obtained from the proximal to the distal esophagus (Figure H, I). Grocott’s methenamine silver stain was negative for fungal pathogens. Based on the clinical scenario, endoscopic findings and pathology images, what is the most likely diagnosis? See the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. Our patient’s dysphagia is secondary to esophageal leukoplakia (also known as “epidermoid metaplasia”). Esophageal biopsies (Figure H, I) reveal marked hyperkeratosis and prominent granular cell layer consistent with esophageal leukoplakia. A repeat upper endoscopy with biopsies was performed without evidence of underlying carcinoma or dysplasia. The patient was placed on twice daily maximum dose proton pump inhibitor therapy. Her symptoms improved. Esophageal dilation was deferred considering extreme mucosal friability and improvement of symptoms with medical therapy. She is enrolled currently in an active surveillance program consisting of repeat upper endoscopies and biopsies for early detection of dysplasia. Esophageal leukoplakia is extremely rare and poorly described in the literature. It is characterized by the presence of mucosal white plaques that cannot be scraped. In a recent case series of esophageal leukoplakia in 18 patients from multiple medical centers, it was noted that the majority of the patients were smokers or exposed to secondhand smoke (61%).1Singhi A.D. Arnold C.A. Crowder C.D. et al.Esophageal leukoplakia or epidermoid metaplasia: a clinicopathological study of 18 patients.Mod Pathol. 2014; 27: 38-43Crossref PubMed Scopus (33) Google Scholar There is an unclear association between esophageal leukoplakia and squamous cell dysplasia/carcinoma. For example, the presence of high grade dysplasia or squamous cell carcinoma in 18 esophageal leukoplakia patients was 17% in 1 series.1Singhi A.D. Arnold C.A. Crowder C.D. et al.Esophageal leukoplakia or epidermoid metaplasia: a clinicopathological study of 18 patients.Mod Pathol. 2014; 27: 38-43Crossref PubMed Scopus (33) Google Scholar Another small series identified 4 patients with epidermoid metaplasia and all 4 had either synchronous or metachronous squamous cell carcinoma.2Ezoe Y. Fujii S. Muto M. et al.Epidermoid metaplasia of the esophagus: endoscopic feature and differential diagnosis.Hepatogastroenterology. 2011; 58: 809-813PubMed Google Scholar All 4 patients in that case series were heavy alcohol drinkers. Our case is unique in that this is a rare condition and our patient lacked risk factors such as smoking or alcohol abuse.

Sa1118 Prospective Multicenter Study of Sleep Disturbance in Patients Who Are Refractory to Daily Proton Pump Inhibitor Therapy and Efficacy of Twice-Daily Rabeprazole

G A A b st ra ct s taking paroxetine . In group B 91 reported a reduction in epigastric pain or other associated symptoms of FD, and 8 patients stopped taking paroxetinefor side effect ,fear and relief of symptoms. 3. At the end of 12 weeks 71 patients in group A reported a reduction in epigastric pain and other associated symptoms of FD, and 28 patients stopped taking paroxetinefor side effects , fear ,relief of symptoms and no obvious improvement. In group B 101 patients reported a reduction in epigastric pain and other associated symptoms of FD, and 9patients stopped taking paroxetine for side effect , fear ,relief of symptoms or no obvious improvement. Conclusion: 1. Double steps reattribution psychotherapy in the integrative model can improve compliance of paroxetine significantly in patients with FD 2. Double steps reattribution integrative model was effective in alleviating the epigastric pain and other associated symptoms of FD and it is better than paroxetine treatment alone significantly ; Increased compliance of Antidepressants may be one of the reasons.

Treatment of Recurrent Vocal Cord Granuloma with Percutaneous Steroid Injection

Treatment of Recurrent Vocal Cord Granuloma with Percutaneous Steroid Injection Vocal cord granulomas are areas of chronic inflammation, usually located near the vocal process, caused by a variety of conditions such as intubation, gastroesophageal reflux disease, and vocal abuse. They are often difficult to eradicate. Treatments range from conservative management using anti-reflux medications, inhaled steroids, and voice therapy, to more invasive measures such as surgical excision, botulinum toxin injection, and steroid injection. Surgical treatment often leads to a high rate of recurrence. Botulinum toxin injections have shown promise in preliminary studies, but are not appropriate for all patients due to potential adverse effects. Percutaneous steroid injection offers a safe, minimally invasive, yet effective method of treating and preventing recurrence of both primary and recurrent vocal cord granulomas. This paper reports successful treatment of a recurrent vocal cord granuloma using percutaneous steroid injection in a patient who failed both medical management and multiple surgical excisions. Complete resolution was seen two months after the second steroid injection. The patient has remained disease free one year from the final treatment, maintained only on daily proton pump inhibitor therapy. This case demonstrates there are multiple options available to treat this disease, and more prospective research is needed to establish a consistent treatment algorithm for all subsets of patients.

Gradual cessation of proton pump inhibitor (PPI) treatment may prevent rebound acid secretion, measured by the alkaline tide method, in dyspepsia and reflux patients

Gastro esophageal reflux disease and ulcer related or non-ulcer dyspepsia, attacks 20% of the Western population. These millions of patients are treated continuously with PPI for different periods, many for many years. Recently, rebound acid hypersecretion was recognized as a major clinical event after cessation of PPI therapy. Sustained hypergastrinemia due to daily PPI therapy causes increased acid-secretory capacity that appears when the drug is stopped. The transient increase in blood and urinary pH following gastric secretion has been termed the alkaline tide phenomenon. Carbonic acid, formed in the presence of the enzyme carbonic anhydrase, neutralizes intracellular hydroxyl ions produced as a result of luminal acid secretion. The bicarbonate generated is removed from the cell via the baso-lateral chloride bicarbonate exchanger. We have shown in several studies that this phenomenon parallels acid secretion. Thus, stimulation of acid secretion with test meal increased base excess maximally after 45min and these changes parallel peak acid output measured in gastric aspirate. We hypothesize that gradual step down cessation of PPI will prevent this clinical relevant event. By measuring alkaline tide after PPI cessation we may prove this hypothesis.

PPI as an Unusual Therapy for Eosinophilic Gastroenteritis

Purpose: Eosinophilic gastroenteritis (EG) is a rare and heterogeneous disease characterized by focal or diffuse eosinophilic infiltration of the GI tract. Its presentation is protean and its incidence unknown. The disease usually involves the stomach and small intestine (rarely the colon) and may be accompanied by peripheral blood eosinophilia. Here we describe a case of EG that presented as iron deficiency anemia (IDA) and mild hypoalbuminemia in a female patient without GI complaints who had complete resolution of her eosinophilic infiltration and associated anemia after empiric initiation of proton pump inhibitor (PPI) therapy. To our knowledge, this is the first case of biopsy proven EG to respond to acid reduction therapy. A 27-year old female presented to our institution with a 10 month history of progressive fatigue and SOB. Investigations revealed a hgb of 6.6 g/dL and iron indices compatible with IDA. Her peripheral eosinophil counts were slightly elevated at 9.7%. She was mildly hypoalbuminemic at 3.2 g/dL. She was transfused PRBC's with marked improvement of her presenting complaints. She was referred for endoscopic evaluation of her IDA. Upper endoscopy revealed erosive gastropathy in the fundus and antrum. Biopsies confirmed chronic inflammation with a significant increase in eosinophils within the lamina propria (up to 100/HPF). As the patient had only seasonal allergies (no overt atopy) and was otherwise asymptomatic, other etiologies for her eosinophilia and IDA including celiac sprue, blood dyscrasias (bone marrow biopsy), infection (H. pylori, parasites), iatrogenic (medication), adrenal insufficiency, and collagen vascular disease were all ruled out. Colonoscopy with random biopsies throughout was negative as was CT imaging and capsule endoscopy. During this extensive work-up and because of a reluctance to initiate immune modulating medications and/or steroids in an asymptomatic patient, we decided to empirically initiate PPI therapy while we completed our investigations. During this time, the patient postponed her workup to return to school. She sent us monthly CBC results which remained normal except for a mildly elevated peripheral eosinophil count. Follow-up upper endoscopy 8 weeks after her initial endoscopy and initiation of PPI therapy revealed complete healing of her gastropathy. Biopsies were normal. To date, the patient remains asymptomatic on daily PPI therapy with normalization of her albumin and resolution of her anemia. The mechanism for this response is unknown but may justify an empiric trial of PPI therapy while conducting the thorough and often lengthy investigations required to diagnosis EG.

Ten-Year Outcome of Laparoscopic and Conventional Nissen Fundoplication

To compare 10 years outcome of a multicenter randomized controlled trial on laparoscopic (LNF) and conventional Nissen fundoplication (CNF), with focus on effectiveness and reoperation rate. LNF has replaced CNF as surgical treatment for gastroesophageal reflux disease (GERD). Decisions are based on equal short-term effectiveness and reduced morbidity, but confirmation by long-term level 1 evidence is lacking. From 1997 to 1999, 177 proton pump inhibitor (PPI)-refractory GERD patients were randomized to undergo LNF or CNF. The 10 years results of surgery on reflux symptoms, general health, PPI use, and reoperation rates, are described. High-resolution manometry, 24-hour pH-impedance monitoring and barium swallow were performed in symptomatic patients only. A total of 148 patients (79 LNF, 69 CNF) participated in this 10-year follow-up study. GERD symptoms were relieved in 92.4% and 90.7% (NS) after LNF and CNF, respectively. Severity of heartburn and dysphagia were similar, but slightly more patients had relief of regurgitation after LNF (98.7% vs. 91.0%; P = 0.030). The percentage of patients using PPIs slowly increased with time in both groups to 26.6% for LNF and 22.4% for CNF (NS). General health (74.7% vs. 72.7%; NS) and quality of life (visual analogue scale score: 65.3 vs. 61.4; NS) improved similarly in both groups. The percentage of patients who would have opted for surgery again was similar as well (78.5% vs. 72.7%; NS). Twice as many patients underwent reoperation after CNF compared with LNF (12 [15.2%] vs. 24 [34.8%]; P = 0.006), including a higher number of incisional hernia corrections (2 vs. 9; P = 0.015). Mean interval between operation and reintervention was longer after CNF (22.9 vs. 50.6 months; P = 0.047). Of the patients who were dependent on daily PPI therapy at 10 years (LNF 10, CNF 10), 7 patients (LNF 3, CNF 4) had recurrent GERD on pH-impedance monitoring, 5 of them with some form of anatomic recurrence. A total of 13 of 20 (65.0%) patients did not have recurrent GERD. Fourteen patients had an abnormal high-resolution manometry. CNF carries a higher risk for surgical reintervention compared with LNF, mainly due to incisional hernia corrections. The 10-year effectiveness of LNF and CNF is comparable in terms of improvement of GERD symptoms, PPI use, quality of life, and objective reflux control. Consequently, the long-term results from this trial lend level 1 support to the use of LNF as the surgical procedure of choice for GERD.

Endoscopic full-thickness plication for the treatment of gastroesophageal reflux disease using multiple Plicator implants: 12-month multicenter study results

The full-thickness Plicator (Ethicon Endosurgery, Sommerville, NJ, USA) was developed for endoscopic treatment of gastroesophageal reflux disease (GERD). The goal is to restructure the antireflux barrier by delivering transmural pledgeted sutures through the gastric cardia. To date, studies using this device have involved the placement of a single suture to create the plication. The purpose of this study was to evaluate the 12-month safety and efficacy of this procedure using multiple implants to restructure the gastroesophageal (GE) junction. A multicenter, prospective, open-label trial was conducted at four tertiary centers. Eligibility criteria included symptomatic GERD [GERD Health-Related Quality-of-Life (GERD-HRQL) questionnaire, off of medication], and pathologic reflux (abnormal 24-h pH) requiring daily proton pump inhibitor therapy. Patients with Barrett's epithelium, esophageal dysmotility, hiatal hernia > 3 cm, and esophagitis (grade III or greater) were excluded. All patients underwent endoscopic full-thickness plication with linear placement of at least two transmural pledgeted sutures in the anterior gastric cardia. Forty-one patients were treated. Twelve months post treatment, 74% of patients demonstrated improvement in GERD-HRQL scores by > or = 50%, with mean decrease of 17.6 points compared with baseline (7.8 vs. 25.4, p < 0.001). Using an intention-to-treat model, 63% of patients had symptomatic improvements of > or = 50%, with mean GERD-HRQL decrease of 15.0 (11.0 vs. 26.0, p < 0.001). The need for daily proton pump inhibitor (PPI) therapy was eliminated in 69% of patients at 12 months on a per-protocol basis, and 59% on an intention-to-treat basis. Adverse events included postprocedure abdominal pain (44%), shoulder pain (24%), and chest pain (17%). No long-term adverse events occurred. Endoscopic full-thickness plication using multiple Plicator implants can be used safely and effectively to improve GERD symptoms and reduce medication use.

The Effects of Once Daily Versus Twice Daily Proton Pump Inhibitor Therapy on NSAID Induced Gastric Ulcers

Purpose: The effects of once daily versus twice daily PPI therapy administered for an average of 12 weeks on gastric ulcer healing was compared. Methods: A retrospective chart review was preformed on adult patients presenting to a large teaching community hospital over a 5 year period (2001–2006) with melena or hematemesis and a history of NSAID use, who underwent endoscopy revealing gastric ulcers. Patients between the ages of 18 and 95 years, with a non-malignant gastric ulcer who had a history of any NSAID use for at least one week prior to presentation were eligible for enrollment. Patients were divided into two groups according to the anti-secretory therapy received. Group 1 comprised of once daily PPI therapy versus group 2 receiving twice daily PPI therapy. The primary endpoint was evidence of gastric ulcer healing during repeat endoscopy at 8 to 12 weeks. Results: 135 patients met our inclusion criteria, of these, 68 received daily PPI therapy while 67 received twice daily therapy. There was no statistical difference in demographics or co-morbidities in either group. The mean ages of the groups were 73 and 72 respectively. 83.3% of patients with active bleeding (P= 0.015) and 67% of patients with visible vessels on endoscopy (P= .216), were prescribed twice daily therapy. The average time for repeat endoscopy was 12.57 weeks for group 1 and 9.82 weeks for group 2. Healing rates of gastric ulcers at repeat endoscopy were 92.6% and 86.5% respectively with no statistical difference (P= .622) using Pearson Chi-square test. Conclusion: Our retrospective chart review revealed no statistical difference in healing rates of NSAID induced gastric ulcers among patients receiving daily versus twice daily PPI therapy. The lower healing rates in patients receiving twice daily group, maybe related to more severe disease and earlier second endoscopy.

Endoscopic Full-Thickness Plication for the Treatment of GERD: 12 Month Follow-Up in the Sham-Controlled Trial

Purpose: To evaluate the safety and efficacy of the NDO Plicator endoscopic procedure for the treatment of symptomatic GERD in a cohort of patients followed out to 12 months from their original participation in a sham-controlled study. Methods: Patients with chronic heartburn and pathologic reflux requiring daily proton pump inhibitor (PPI) therapy were enrolled. Excluded from treatment were patients with esophageal dysmotility, esophagitis grade III or IV (Savary-Miller), Barrett's epithelium, and hiatus hernia >2 cm. All patients received a single, endoscopically placed full-thickness plication in the anterior gastric cardia. The primary study endpoint was ≥50% improvement in GERD health-related quality of life (HRQL) score. Secondary end points included VAS, SF-36, GERD medication use, and esophageal acid exposure. Results: A total of 148 patients were treated at 14 study sites. No re-treatments were performed. Twelve-months post-plication, 59/96 patients (62%) had improved their GERD-HRQL score by at least 50%. Median percent change in GERD-HRQL score (62%), VAS score (46%), heartburn score (67%) and regurgitation score (50%) were all significantly improved compared to off meds baseline values. The need for daily PPI therapy was either eliminated or reduced by at least half in 63% of patients at 12-months post-treatment. There were no new or late onset adverse events. Conclusion: At 12-months post-procedure, the cohort originally treated with full-thickness plication with the Plicator and the cross-over group treated after sham showed the endoscopic treatment to be safe and effective in reducing GERD symptoms and medication use.

Endoscopic full-thickness plication for the treatment of GERD: long-term multicenter results

The purpose of the present study was to assess the long-term safety and durability of effect for endoscopic full-thickness plication for the treatment of symptomatic gastroesophageal reflux disease (GERD). The Plicator (NDO Surgical, Inc., Mansfield, MA) used delivers a transmural suture through the gastric cardia to restructure the antireflux barrier. Published reports have shown the Plicator procedure to be effective in reducing GERD symptoms and medication use at 1 year post-plication. Twenty-nine patients with chronic heartburn requiring maintenance daily anti-secretory therapy were treated at five sites. Patients received a single full-thickness plication in the gastric cardia 1cm below the gastroesophageal junction (GE) junction. Re-treatments were not permitted. Patients were evaluated at baseline for GERD symptoms and medication use. Intermediate (12 month) and long-term subject follow-up (median follow-up: 36.4 months; range, 31.2-43.9 months) were completed to evaluate procedure safety and durability of effect. Twenty-nine patients completed the 12-month and 36-month follow-up. All procedure-related adverse events occurred acutely, and no new events were observed during extended follow-up. At 36-months post-procedure, 57% (16/28) of baseline proton pump inhibitor (PPI)-dependent patients remained off daily PPI therapy. Treatment effect remained stable from 12- to 36-months, with 21/29 patients off daily PPI at 12 months compared to 17/29 patients at 36-months. Median GERD- Health Related Quality of Life (HRQL) scores remained significantly improved at 36 months versus baseline off-meds scores (8 versus 19, p < 0.001). In addition, the proportion of patients achieving > or = 50% improvement in GERD-HRQL score was consistent from 12 months (59%) to 36 months (55%). Endoscopic full-thickness plication can reduce GERD symptoms and medication use for at least 3-years post-procedure. Treatment effect is stable from 1 to 3 years, and there are no long-term procedural adverse effects.

Review article: alternative approaches to the long‐term management of GERD

Although proton-pump inhibitors are highly effective for the treatment of gastro-oesophageal reflux disease, there are issues with long-term maintenance therapy: not all patients require full daily dose for maintenance treatment, some patients are reluctant to take long-term daily medication, and long-term PPI therapy is inadequate for some patients. This article aims to review alternatives to daily proton-pump inhibitor therapy for the long-term management of gastro-oesophageal reflux disease, including intermittent or on-demand proton-pump inhibitor use, as well as endoscopic and surgical options. On-demand proton-pump inhibitor therapy has demonstrated efficacy in achieving acceptable symptom control, healing and maintenance of quality of life for a proportion of patients with gastro-oesophageal reflux disease. Endoscopic antireflux procedures can reduce the need for proton-pump inhibitor therapy, but safety and durability of these procedures require more study. Surgical treatment of gastro-oesophageal reflux disease in properly selected patients has demonstrated efficacy in reducing symptoms and the need for proton-pump inhibitor therapy; however, long-term follow-up suggests that it is not a permanent solution for many patients. While daily proton-pump inhibitor therapy remains the main treatment regimen option for most patients with gastro-oesophageal reflux disease, on-demand therapy may prove effective for many patients. Endoscopic anti-reflux therapies and surgery are options for patients who prefer nonpharmacological treatment, but experience is limited at this point in time for the former.

PROTON PUMP INHIBITORS HAVE A MORE PROFOUND EFFECT ON GASTRIC ACID SECRETION IN FEMALE AND OLDER GERD PATIENTS

Purpose: Proton pump inhibitor (PPI) therapy is believed to be equally effective in all patients with upper GI symptoms. However, data is lacking on the degree of PPI efficacy in various subgroups including males, females, the young and old where acid secretion rates may differ (Gas-troenterology 1991; 101: 977-990). Therefore, our aim was to assess the influence of gender and age in PPI inhibition of basal and pentagas-trin (Pg)-stimulated gastric acid secretion (GAS) in symptomatic GERD patients. Methods: A total of 36 GAS studies were conducted in 15 male (22–69 y) and 10 female (35–67 y) HP-negative GERD patients on a daily AM dose of PPI therapy for 8–10 days. Basal and Pg (6 mcg/kg, s.c.)-stimulated GAS was measured during the trough period (22–24 h post-dose). Gastric acid was continuously aspirated via a nasogastric tube, aspirate volume recorded, [H+] measured by titration to pH 7.0, pH determined and GAS calculated. Results: In females, PPIs had a more significant effect on both basal and Pg-stimulated GAS compared to males (Table; median data; *+P <0.03). The same was true for inhibition of Pg-stimulated GAS in older (age >44 y) compared to younger (age <44 y) patients (Table). Differences in GAS were due to significant decreases in gastric [H] and volume secretion in female and older patients (Table). Interestingly, median intragastric pH under basal conditions was pH 2.0 or less during steady state conditions. Furthermore, median Pg-stimulated gastric volumes were over 100 ml/h in males and younger patients.Table: PPI-inhibition of GAS in GERD PatientsConclusions: In GERD patients on daily PPI therapy: 1. PPIs have a more profound effect on GAS in female and older subjects; and 2. Despite steady-state conditions, significant gastric acid secretion was noted. We speculate that these findings may explain the variability in PPI efficacy in GERD as is seen in clinical practice, and may have implications in nocturnal acid breakthrough.