Healing Of Reflux Esophagitis Research Articles

Vonoprazan in the management of erosive oesophagitis and peptic ulcer-induced medication: a systematic review.

IntroductionVonoprazan has been found to promote a better antisecretory effect addressing acid-related diseases’ unmet needs.AimTo assess if vonoprazan effectively treats patients diagnosed with gastroesophageal reflux disease esophagitis or with peptic ulcers induced by chronic use of aspirin or non-steroidal anti-inflammatory drugs.Material and methodsA literature search was conducted (April/2021) using Medline via PubMed, Cochrane library, Lilacs, Scielo, and Centre for Reviews and Dissemination electronic databases.ResultsWe retrieved 55 titles. Of these, 13 met the eligibility criteria and were included in this review. Of these 13 articles, 4 were prospective cohort studies, 1 was a follow-up analysis of a preceding prospective study, 1 was a retrospective cohort study, and 6 were randomized clinical trials.ConclusionsOur findings suggest that vonoprazan was effective and non-inferior to proton pump inhibitors in healing and maintaining healed reflux oesophagitis, leading to faster symptom relief. Vonoprazan may also be considered for preventing aspirin- or non-steroidal anti-inflammatory drug-related peptic ulcer recurrence.

Efficacy of Vonoprazan for 48-Week Maintenance Therapy of Patients with Healed Reflux Esophagitis

Aims: We aimed to evaluate the efficacy of vonoprazan (VPZ) as maintenance therapy for healed reflux esophagitis (RE). Methods: We enrolled 74 patients diagnosed with RE with frequency scale for the symptoms of gastroesophageal reflux disease (FSSG) total score ≥8 after at least 8 weeks of treatment with standard proton pump inhibitors (PPIs). These patients were switched to VPZ 20 mg for 4 weeks. We also enrolled 71 patients with no endoscopic evidence of erosive esophagitis who received maintenance therapy with VPZ 10 mg for 48 weeks. The primary end point was the proportion of patients who maintained healed RE refractory to PPIs after 48 weeks of maintenance therapy with on demand 10 mg VPZ. Secondary assessment included the proportion of patients with symptomatic nonrelapse at 48 weeks. Results: Fifty patients successfully completed 48-week maintenance therapy. Maintenance therapy with VPZ 10 mg prevented the relapse of esophageal mucosal breaks in 43 (86.0%) of 50 patients at 48 weeks. During the 48-week maintenance therapy, symptomatic nonrelapse rate for acid reflux-related symptom score of FSSG and acid reflux score of Gastrointestinal Symptom Rating Scale at 48 weeks were 70.0 and 72.0%, respectively. No serious adverse events were reported during the study. Conclusion: VPZ 10 mg is clinically effective for maintenance of healed RE for 48 weeks.

Efficacy and Safety Profile of Z-215 (Azeloprazole Sodium), a Proton Pump Inhibitor, Compared with Rabeprazole Sodium in Patients with Reflux Esophagitis: A Phase II, Multicenter, Randomized, Double-Blind, Comparative Study

BackgroundThe metabolism of many proton pump inhibitors is influenced by CYP2C19 genotype, which is a limitation of their use. ObjectivesTo determine the efficacy and safety profile of Z-215 (azeloprazole sodium) as initial treatment for reflux esophagitis (RE), dose response, and optimal dose compared with rabeprazole sodium (RPZ). MethodsWe conducted an exploratory, multicenter, randomized, double-blind, parallel-group study in Japan. Patients with RE aged ≥20 years were enrolled and randomly assigned to receive 10, 20, or 40 mg Z-215 or 10 mg RPZ (1:1:1:1), and orally administered the respective drug for 8 weeks. The primary efficacy end point was the endoscopic healing rate after 8 weeks of treatment (at Week 8). We also assessed the effects of CYP2C19 genotype. Safety end points were the incidence of adverse events and adverse drug reactions. ResultsFive hundred three patients received the study drugs (10 mg Z-215: 125 patients, 20 mg Z-215: 126 patients, 40 mg Z-215: 126 patients, and 10 mg RPZ: 126 patients). The endoscopic healing rate at Week 8 was above 95% in all groups (10 mg Z-215: 95.2%, 20 mg Z-215: 96.8%, 40 mg Z-215: 95.2%, and 10 mg RPZ: 96.8%). The endoscopic healing rate and serum gastrin levels of the Z-215 groups were not influenced by CYP2C19 genotype. In patients with Grade C/D, the endoscopic healing rate at Week 4 was slightly higher in the 40-mg Z-215 group compared with the other groups. Incidences of adverse events/adverse drug reactions did not markedly differ between the Z-215 and 10-mg RPZ groups. ConclusionsZ-215 was as effective and well tolerated as 10 mg RPZ in the treatment of RE in this selected population. CYP2C19 genotype status may not influence the efficacy and safety of Z-215. There were no clear dose–response effects between Z-215 doses in the endoscopic healing of RE. These findings suggest that Z-215 may be 1 option for the initial treatment of RE. ClinicalTrials.gov identifier: NCT 02463643.

Efficacy of vonoprazan for 24-week maintenance therapy of patients with healed reflux esophagitis refractory to proton pump inhibitors.

The aim of the present study was to evaluate the efficacy of a potassium-competitive acid blocker (P-CAB), vonoprazan, for the maintenance therapy of healed reflux esophagitis (RE). A total of 60 patients were enrolled in this open-label, single-center, prospective study. All patients were diagnosed with RE with a frequency scale for the symptoms of gastroesophageal reflux disease (FSSG) total score ≥8 following treatment with standard proton pump inhibitors (PPIs) for a minimum of 8 weeks. Standard PPI treatment was switched to vonoprazan 20 mg once daily for 4 weeks. A total of 52 patients, who had no endoscopic evidence of erosive esophagitis following vonoprazan treatment, received maintenance therapy with vonoprazan 10 mg once daily for 24 weeks. Symptoms were evaluated using the FSSG and Gastrointestinal Symptom Rating Scale (GSRS). Upper gastrointestinal endoscopies were performed following 24 weeks of maintenance therapy. The primary endpoint was to determine the proportion of patients who exhibited maintenance of healed RE refractory to PPIs following 24 weeks of maintenance therapy with vonoprazan 10 mg once daily. Secondary endpoints included evaluation of the proportion of patients with symptomatic non-relapse at 24 weeks. Maintenance therapy with vonoprazan 10 mg once daily prevented relapse of esophageal mucosal breaks in 37/43 (86.0%) patients at 24 weeks. However, the number of patients with symptomatic relapse was 1 (1.9%) and 4 (7.7%) at 4 and 8 weeks, respectively. A total of 4 patients were withdrawn due to loss to follow-up. At the end of the 24-week maintenance period, the symptomatic non-relapse rate for acid reflux-associated and dysmotility symptom FSSG scores were 86.5 and 80.8%, respectively. Furthermore, the symptomatic non-relapse rate for reflux, abdominal pain, indigestion, diarrhea, and constipation GSRS scores at 24 weeks were 86.5, 80.8, 75.0, 71.2 and 76.9%, respectively. No serious adverse events were reported during the study. The mean gastrin level was 1,059 pg/ml. In conclusion, the results of the present study indicate that vonoprazan 10 mg once daily is effective for 24-week maintenance therapy of healed RE refractory to PPIs.

The added diagnostic value of postreflux swallow-induced peristaltic wave index and nocturnal baseline impedance in refractory reflux disease studied with on-therapy impedance-pH monitoring.

On-therapy impedance-pH monitoring in proton pump inhibitor (PPI)-refractory gastroesophageal reflux disease (GERD) yielded conflicting results. We aimed to assess the diagnostic value of postreflux swallow-induced peristaltic wave (PSPW) index and mean nocturnal baseline impedance (MNBI) in PPI-refractory heartburn. On-therapy impedance-pH tracings from 189 consecutive patients with PPI-refractory heartburn were blindly reviewed. Patients were subdivided into refractory reflux esophagitis (RRE), healed reflux esophagitis (HRE), non-erosive reflux disease (NERD), and functional heartburn (FH) according to endoscopic and conventional impedance-pH findings. The diagnostic accuracy of PSPW index and MNBI in separating NERD from FH was assessed with receiver-operating-characteristic (ROC) analysis. Objectively documented persistent reflux remission at 3-year follow-up in 53 patients who underwent laparoscopic fundoplication served to evaluate PSPW index and MNBI as independent predictors of PPI-refractory GERD confirmed by positive surgical outcome. Median PSPW index and MNBI values were significantly lower in 39 RRE (16%; 1145Ω) than in 41 HRE (25%; 1741Ω) and in 68 NERD (29%; 2374Ω) patients, and in all three GERD subgroups compared to 41 FH cases (67%; 3488Ω) (P<.008). At ROC analysis, comparing NERD to FH the area under the curve was 0.886 with PSPW index and 0.677 with MNBI (P=.005). PSPW index was an independent predictor of PPI-refractory GERD (odds ratio 0.6983, P=.012). At on-therapy impedance-pH monitoring, PSPW index and MNBI efficiently distinguish PPI-refractory NERD from FH. The PSPW index represents an independent predictor of PPI-refractory GERD.

Does the healing of the esophageal mucosa improve the function of the esophageal submucosal and salivary glands?

The esophageal pre-epithelial barrier encompasses components of secretions from both the esophageal submucosal and salivary glands. We demonstrated, in patients with reflux esophagitis (RE), significantly diminished luminal release of esophageal epidermal growth factor (EGF). The rate of luminal release of esophageal prostaglandin E2 (PGE2 ) was significantly higher compared with controls and significantly declined after healing of RE. Patients with RE also exhibited significant declines in esophageal mucin secretion; however, after healing of RE with rabeprazole, this rate increased significantly. The rate of salivary EGF and bicarbonate secretion in patients with RE was significantly lower than in controls. We have demonstrated that mastication of tasteless parafilm, which could be substituted with sugarless chewing gum in the clinical scenario, resulted in profound and significant increases in the rate of secretion of salivary protective factors, such as bicarbonate, mucin, protein, EGF, and PGE2 , in patients with RE. Our data clearly indicate that there is a relationship between the form or the structure of the esophageal mucosa and the secretory function of not only the esophageal submucosal glands but also the salivary glands. Application of masticatory stimulation in a clinical scenario may also have some therapeutic potential.

Potassium-competitive acid blockers: Advanced therapeutic option for acid-related diseases.

Acid-related diseases (ARDs), such as peptic ulcers and gastroesophageal reflux disease, represent a major health-care concern. Some major milestones in our understanding of gastric acid secretion and ARD treatment reached during the last 50years include 1) discovery of histamine H2-receptors and development of H2-receptor antagonists, 2) identification of H+,K+-ATPase as the parietal cell proton pump and development of proton pump inhibitors (PPIs), and 3) identification of Helicobacter pylori (H. pylori) as the major cause of peptic ulcers and development of effective eradication regimens. Although PPI treatments have been effective and successful, there are limitations to their efficacy and usage, i.e. short half-life, insufficient acid suppression, slow onset of action, and large variation in efficacy among patients due to CYP2C19 metabolism. Potassium-competitive acid blockers (P-CABs) inhibit H+,K+-ATPase in a reversible and K+-competitive manner, and exhibit almost complete inhibition of gastric acid secretion from the first dose. Many pharmaceutical companies have tried to develop P-CABs, but most of their clinical development has been discontinued due to safety concerns or a similar efficacy to PPIs. Revaprazan was developed in Korea and was the first P-CAB approved for sale. Vonoprazan, approved in 2014 in Japan, has a completely different chemical structure and higher pKa value compared to other P-CABs, and exhibits rapid onset of action and prolonged control of intragastric acidity. Vonoprazan is an effective treatment for ARDs that is especially effective in healing reflux esophagitis and for H. pylori eradication. P-CABs, such as vonoprazan, promise to further improve the management of ARDs.

Randomised clinical trial: transoral incisionless fundoplication vs. sham intervention to control chronic GERD.

Until recently only two therapeutic options have been available to control symptoms and the esophagitis in chronic gastro-oesophageal reflux disease (GERD), i.e. lifelong proton pump inhibitor (PPI) therapy or anti-reflux surgery. Lately, transoral incisionless fundoplication (TIF) has been developed and found to offer a therapeutic alternative for these patients. To perform a double-blind sham-controlled study in GERD patients who were chronic PPI users. We studied patients with objectively confirmed GERD and persistent moderate to severe GERD symptoms without PPI therapy. Of 121 patients screened, we finally randomised 44 patients with 22 patients in each group. Those allocated to TIF had the TIF2 procedure completed during general anaesthesia by the EsophyX device with SerosaFuse fasteners. The sham procedure consisted of upper GI endoscopy under general anaesthesia. Neither the patient nor the assessor was aware of the patients' group affiliation. The primary effectiveness endpoint was the proportion of patients in clinical remission after 6-month follow-up. Secondary outcomes were: PPI consumption, oesophageal acid exposure, reduction in Quality of Life in Reflux and Dyspepsia and Gastrointestinal Symptom Rating Scale scores and healing of reflux esophagitis. The time (average days) in remission offered by the TIF2 procedure (197) was significantly longer compared to those submitted to the sham intervention (107), P<0.001. After 6months 13/22 (59%) of the chronic GERD patients remained in clinical remission after the active intervention. Likewise, the secondary outcome measures were all in favour of the TIF2 procedure. No safety issues were raised. Transoral incisionless fundoplication (TIF2) is effective in chronic PPI-dependent GERD patients when followed up for 6 months. Clinicaltrials.gov: CT01110811.

Efficacy of Lafutidine Versus Famotidine in Patients with Reflux Esophagitis: A Multi-Center, Randomized, Double-Blind, Non-inferiority Phase III Trial

There has been no study on the efficacy of lafutidine for patients with reflux esophagitis in Korea. To evaluate the efficacy of a new-generation histamine-2 receptor antagonist, lafutidine, in comparison with famotidine in patients with reflux esophagitis. This was a randomized, double-blind, non-inferiority trial enrolling patients with erosive esophagitis. The efficacy and safety of 20 mg lafutidine (treatment group) were compared with those of 40 mg famotidine (control group) and 20 mg omeprazole (reference group). The primary endpoint was the complete healing rates of reflux esophagitis on endoscopy after 8 weeks of treatment. The non-inferiority margin was assumed to be -15 %. The healing rates of reflux esophagitis on endoscopy after 8 weeks of treatment were 70.14 % (101/144) in the lafutidine, 63.45 % (92/145) in the famotidine, and 85.71 % (126/147) in the omeprazole group. The difference in healing rates between the lafutidine and famotidine groups was 6.69 % (95 % confidence interval = [-4.14 to 17.52]). In addition, lafutidine was superior to famotidine in clinical improvement (53.73 % vs. 39.55 %, P = 0.0200). Lafutidine was non-inferior to famotidine in healing of reflux esophagitis. Lafutidine, however, was superior to famotidine in terms of symptom relief of reflux esophagitis.

Mo1066 A Multi-Center, Randomized, Double Blinded, Phase 4 Clinical Trial to Assess the Efficacy and Cost Effectiveness of Omeprazole Compare to Rabeprazole in the Maintenance Therapy of Patients With Gastroesophageal Reflux Disease

Background and Aims: Due to recurring nature of GERD, Most patients require long term maintenance therapy and continuous medication of proton pump inhibitor (PPI) is an adequate option for patients with erosive esophagitis. The aim of this study was to evaluate the efficacy and cost minimization analysis of omeprazole 10 mg once daily and rabeprazole 10 mg once daily for 24 weeks in the maintenance of remission Methods:This is randomized, open-label study enrolled 279 patients with erosive esophagitis A or B (LA classification) and typical GERD symptoms. Patients who showed complete endoscopic and symptomatic healing after 8 weeks PPI treatment were randomly allocated to maintenance treatment with omeprazole 10mg once daily or rabeprazole 10mg once daily for 42 weeks. The primary efficacy endpoint was the proportion of patients with symptomatic remission at 42 weeks. Secondary assessments included healing of reflux esophagitis, severity and frequency of reflux symptoms and cost-minimization analysis in the maintenance phase Results:At the end of 42 weeks of maintenance therapy, 96.4% of omeprazole treated and 95.1% of rabeprazole treated patients remained symptom free (P>0.05). Omeprazole and rabeprazole were also similarly efficacious in terms of endoscopic non-relapse rate for RE with 93.3% of patients on omeprazole and 97.5% of patients of rabeprazle. (P>0.05) Two drugs were also comparable with regard to severity and frequency of reflux symptoms duringmaintenance phase. (P>0.05) In the cost-minimization analysis, The mean total costs per patient for remaining symptom free within 6 months was 241,775 won in omeprazole and 287,115 won in rabeprazole, respectively.(as if 24 November 2011, 1 USD= 1,176.33 won) Conclusions:Omeprazole 10mg appeared to have a similar efficacy in maintaining symptomatic remission as rabeprazole 10 mg, but had a lower total cost per patient than rabeprazole 10mg.

Mo1069 Effect of Oral Administration of a New Proton Pump Inhibitor E3710 on 24-h Intra-Gastric pH in Japanese Subjects

Background and Aims: Due to recurring nature of GERD, Most patients require long term maintenance therapy and continuous medication of proton pump inhibitor (PPI) is an adequate option for patients with erosive esophagitis. The aim of this study was to evaluate the efficacy and cost minimization analysis of omeprazole 10 mg once daily and rabeprazole 10 mg once daily for 24 weeks in the maintenance of remission Methods:This is randomized, open-label study enrolled 279 patients with erosive esophagitis A or B (LA classification) and typical GERD symptoms. Patients who showed complete endoscopic and symptomatic healing after 8 weeks PPI treatment were randomly allocated to maintenance treatment with omeprazole 10mg once daily or rabeprazole 10mg once daily for 42 weeks. The primary efficacy endpoint was the proportion of patients with symptomatic remission at 42 weeks. Secondary assessments included healing of reflux esophagitis, severity and frequency of reflux symptoms and cost-minimization analysis in the maintenance phase Results:At the end of 42 weeks of maintenance therapy, 96.4% of omeprazole treated and 95.1% of rabeprazole treated patients remained symptom free (P>0.05). Omeprazole and rabeprazole were also similarly efficacious in terms of endoscopic non-relapse rate for RE with 93.3% of patients on omeprazole and 97.5% of patients of rabeprazle. (P>0.05) Two drugs were also comparable with regard to severity and frequency of reflux symptoms duringmaintenance phase. (P>0.05) In the cost-minimization analysis, The mean total costs per patient for remaining symptom free within 6 months was 241,775 won in omeprazole and 287,115 won in rabeprazole, respectively.(as if 24 November 2011, 1 USD= 1,176.33 won) Conclusions:Omeprazole 10mg appeared to have a similar efficacy in maintaining symptomatic remission as rabeprazole 10 mg, but had a lower total cost per patient than rabeprazole 10mg.

Combination of angiotensin II receptor blockers promotes proton pump inhibitor-based healing of reflux esophagitis

Several studies have described factors associated with the failure of proton pump inhibitors (PPIs) to effect endoscopic healing of reflux esophagitis (RE), but few studies have addressed factors promoting PPI-based endoscopic healing. We performed post hoc analysis of a multicenter prospective cohort of RE patients to identify factors encouraging endoscopic healing of this disorder. Patients with RE received 10 or 20 mg rabeprazole for 8 weeks, and endoscopic findings before and after treatment were studied. To evaluate the effects of patient background factors on endoscopic healing, we performed multiple logistic regression analysis and determined the respective odds ratios (ORs) and 95% confidence intervals (CIs). A total of 454 patients who underwent endoscopy at baseline and again at week 8 were included in the analysis. After 8 weeks of treatment, improvement in endoscopic findings was observed in 94.1% (427/454) of patients, and endoscopic healing was seen in 76.7% (348/454). Multiple logistic regression analysis revealed that a combination of angiotensin II receptor blockers (ARBs) had a significant positive impact on endoscopic healing (OR 3.9, 95% CI 1.411-10.903), but no significant positive relationship was seen for other concomitant drugs such as nonsteroidal anti-inflammatory drugs and calcium channel blockers. Severe RE at baseline (OR 0.365, 95% CI 0.281-0.475) and PPI therapy prior to enrollment (OR 0.154, 95% CI 0.052-0.453) were found to have significant negative effects on endoscopic healing. Concomitant use of ARBs may promote endoscopic healing of RE treated with PPIs.

Comparison of the Efficacy and Safety of Pantoprazole Magnesium and Pantoprazole Sodium in the Treatment of Gastro-Oesophageal Reflux Disease

Proton pump inhibitors (PPIs) are well established as first-line agents for the treatment of moderate-to-severe gastro-oesophageal reflux disease (GORD). Although all PPIs heal oesophageal lesions and provide symptomatic relief, breakthrough symptoms may occur as acidity levels rebound. Pantoprazole magnesium (pantoprazole-Mg) has a longer elimination half-life than pantoprazole sodium (pantoprazole-Na), resulting in prolonged drug exposure. This study compares the clinical efficacy and safety of once-daily pantoprazole-Mg 40 mg with that of once-daily pantoprazole-Na 40 mg in the management of GORD. This was a randomized, double-blind, controlled, multicentre study of non-inferiority design in outpatients with GORD. The study was conducted in 53 centres in Germany from 12 May 2003 to 18 September 2003. Male or female outpatients (aged ≥18 years) with endoscopically confirmed GORD stage I-III (according to the Savary-Miller classification modified by Siewert) were enrolled. Using a computer-generated randomization list, patients were randomized to treatment with pantoprazole-Mg 40 mg plus placebo or pantoprazole-Na 40 mg plus placebo, both given once daily for 4 or 8 weeks depending on healing of oesophagitis. The primary objective was endoscopic healing at 8 weeks. The intent-to-treat (ITT) group consisted of 636 patients (322 receiving pantoprazole-Mg and 314 receiving pantoprazole-Na). Endoscopically confirmed healing of reflux oesophagitis after 8 weeks occurred in 87.3% (95% CI 83.1, 90.7) of patients receiving pantoprazole-Mg and 85.0% (95% CI 80.6, 88.8) of patients receiving pantoprazole-Na (ITT population). The lower bound of the 95% CI for the between-group treatment difference was -1.3, which was within the predefined margin of non-inferiority of -10% to 0%. Healing rates after 4 weeks were superior in the pantoprazole-Mg group (72.7% [95% CI 67.5, 77.5]) compared with the pantoprazole-Na group (66.2% [95% CI 60.7, 71.5]), and the one-sided (lower bound) of the 95% CI for the difference between healing rates for the two treatments was within the predefined non-inferiority margin of -10% to 0%. Both treatments had a similar effect on GORD healing in subgroups of patients based on baseline oesophagitis grade and Helicobacter pylori status. Pantoprazole-Mg had similar efficacy to pantoprazole-Na in relieving a broad range of GORD-related symptoms across the course of the study, although symptomatic relief at 4 weeks was numerically higher in the pantoprazole-Mg group than in the pantoprazole-Na group (statistical analyses were not performed). Both treatments were well tolerated; most adverse events were of mild or moderate severity and unrelated to the study medication, and there were no unexpected safety concerns. Pantoprazole-Mg is clinically as effective and well tolerated as pantoprazole-Na in the treatment of GORD stages I-III, demonstrating non-inferiority for oesophageal healing at 8 weeks and superior healing rates at 4 weeks associated with high levels of symptomatic relief.

Review of the persistence of gastroesophageal reflux disease in children, adolescents and adults: does gastroesophageal reflux disease in adults sometimes begin in childhood?

Objective. Understanding the natural history and outcomes of gastroesophageal reflux disease (GERD) in children could help to identify patients at risk of having GERD complications during adulthood. This review aimed to assess evidence of whether GERD in children or adolescents persists into adulthood. Material and methods. PubMed searches (1966–2010) identified longitudinal studies of GERD extending from childhood/infancy into adulthood, as well as longitudinal studies within pediatric age groups. Results. In one study, heartburn during childhood was more often recalled by adults with reflux symptoms than by those without (30% vs. 9%; p < 0.001), as was medication or surgery for GERD (both p < 0.01). Another study found that GERD symptoms were more common in adults diagnosed with reflux esophagitis during childhood/adolescence than in those who were not (46% vs. 30%). Regurgitation during infancy increased the risk of feeding problems after 1 year (odds ratio 4.2 (95% confidence interval: 1.4–12.0)) and of reflux symptoms at 9 years of age (relative risk 2.3 (95% confidence interval: 1.3–4.0)). In one study, abnormal esophageal histology persisted in infants after 12 months without reflux symptoms. A proportion (59–100%: three studies) of patients with reflux symptoms and/or reflux esophagitis during the pediatric years still required treatment after 1–8 years. In another study, however, just 7% of patients with healed reflux esophagitis relapsed after 9 months without treatment. Conclusion. The limited available evidence suggests that some infants, children, and adolescents with GERD are more likely than those without GERD to have symptoms later in life.

Transoral Incisionless Fundoplication Offers High Patient Satisfaction and Relief of Therapy-Resistant Typical and Atypical Symptoms of GERD in Community Practice

This retrospective study evaluated clinical outcomes in 124 consecutive gastroesophageal reflux disease (GERD) patients who underwent transoral incisionless fundoplication (TIF) at 2 community hospitals. Out of 123 patients treated successfully, 110 gave consent (74% female, median age 60 [range 21-87] years, body mass index 27.5 [19.0-47.9]). At a median 7-month follow-up (range 5-17), typical and atypical symptom scores were normalized in 75% to 80% of patients, proton pump inhibitors (PPIs) were completely discontinued by 93%, and 83% were satisfied with their current health condition. Endoscopy in 53 patients revealed Hill grade I tight valves in 89% of the cases, reduced hiatal hernia in 33/34 (97%), and healed reflux esophagitis in 25/30 (83%). Based on global analysis, 72% of the patients were in remission, 20% improved symptomatically, and only 8% had ongoing GERD. These results supported the safety and efficacy of TIF as well as encouraged its application as an alternative treatment of GERD refractory to PPIs.

Acid exposure and esophageal motility following laparoscopic fundoplication: A comparative randomized study.

Review: Gastro-esophageal reflux disease is one of the most widely spread diseases allover the world. The principle underlying its surgical management is the creation of a mechanical antireflux barrier between the esophagus and the stomach through the creation of either a total (360 degree), or partial anterior or posterior fundal wraps around the lower esophageal end. The ability of surgery to mechanically control the reflux has been documented. The pathogenesis of gastro-esophageal reflux disease is essentially a motility-related problem with varying contributory elements. The role of different techniques in correcting the underlying motility disorder has been little studied in the randomised literature. Aim: The aim of this study was to compare the ability of the laparoscopic partial posterior and the laparoscopic total fundoplication techniques in objectively controlling the reflux and correcting the underlying esophageal motility disorder in gastro-esophageal reflux patients on the mid-term. Patients and methods: In the period between June 1998 and July 2007, 40 patients considered for antireflux surgery in the department of surgery, Tanta University Hospital, were prospectively recruited and randomised to undergo either laparoscopic total (Nissen) or laparoscopic partial posterior (Toupet) fundoplication. In addition to the clinical follow-up, objective follow up through esophageal manometry, 24-h pH monitoring and upper gastrointestinal endoscopy were performed 24 months after operation and compared to the same data recorded preoperatively. Results: Both the total and the partial posterior fundoplication techniques showed excellent control of heartburn and regurgitation postoperatively. This correlated well with the postoperative endoscopic findings, where both techniques were equally effective in correcting hiatus hernias and healing reflux esophagitis. In the Nissen group, the lower esophageal resting pressure significantly increased postoperatively from a median of 23, to 33 mmHg (p 0.05). Length of the abdominal component was significantly increased postoperatively from a median of 3 to 4 cm and from a median of 2 to 4 cm in the Nissen and Toupet groups respectively (p 0.05). No significant changes were found in the esophageal body contraction amplitude on comparing the pre and postoperative values in both groups (p>0.05). The median total acid exposure time in the Nissen and Toupet groups was significantly reduced from a preoperative 13% to 1% and from 17 % to 0% respectively, with similar reduction in the number of pH proven reflux episodes from a median of 24 to 2 and from 30 to 2 respectively (p < 0.01). The small number of cases with Barrett’s metaplasia in our study made it difficult to draw hard conclusions on the difference between the two surgical techniques in this particular type of patients. Conclusion: The partial posterior and total fundoplication techniques are equally effective in restoring the lower esophageal pressure profile and in objectively controlling the reflux on the mid-term. No changes in the esophageal body contraction amplitude could be found with either technique. No objective advantages could be demonstrated for either technique to support a tailored approach.

Maintenance Treatment With Proton Pump Inhibitors for Reflux Esophagitis in Pediatric Patients: A Systematic Literature Analysis

Short-term treatment with a proton pump inhibitor (PPI) is effective for healing reflux esophagitis and improving reflux symptoms in pediatric patients. Our aim was to assess the efficacy and tolerability of maintenance PPI treatment after healing of reflux esophagitis in pediatric patients. Systematic searches of MEDLINE, Excerpta Medica database, and recent conference abstracts. Five studies evaluated the efficacy of PPI maintenance therapy (6- to 90-month follow-up) in pediatric patients after healing of reflux esophagitis. Three found no relapse of reflux esophagitis or reflux symptoms during PPI maintenance therapy; however, a low relapse rate (1/14) was also found in the placebo group of the only prospective controlled study. Two of the 5 studies (both prospective) reported relapse of reflux esophagitis at half the original healing dose of omeprazole (7 of 51 patients relapsed after 3 months; 8 of 32 within 21 months), which resolved again in most patients when the healing dose or higher was given. Four studies evaluated relapse of reflux esophagitis and/or reflux symptoms after stopping PPI therapy. Reflux symptoms recurred in 18% to 76% of patients across all 4 studies. In the 4 studies that assessed the safety of PPI maintenance therapy, adverse events were infrequent and of low severity. Pediatric patients with gastroesophageal reflux disease and certain chronic comorbidities appear to have the greatest need of maintenance PPI treatment after healing of reflux esophagitis. In patients requiring maintenance therapy, PPIs appear to be well tolerated and effective in maintaining remission of reflux esophagitis and reflux symptoms.

Bringing GERD Management up to PAR-2

Proton pump inhibitors (PPIs) are extremely effective for mucosal healing of reflux esophagitis, but less so for relieving the symptom of heartburn. PPIs block the secretion of gastric acid, the caustic effects of which have been assumed to be the primary culprit in the pathogenesis of reflux esophagitis. However, mounting data suggest that reflux-stimulated, immune-mediated mechanisms may underlie the development of esophagitis in patients with gastroesophageal reflux disease (GERD). Thus, the future of GERD therapy, particularly for patients who are refractory to PPIs, may be the targeting of proteins such as proteinase-activated receptor-2, which have central roles in the generation of immune-mediated esophageal mucosal damage and in eliciting the symptom of heartburn.

Prevention of Relapse of Healed Reflux Esophagitis is Related to the Duration of Intragastric pH&gt;4

Proton pump inhibitors (PPIs) are the preferred treatment for maintenance of healed reflux esophagitis (RE). However, little is known regarding the relationship between prevention of RE relapse and degree of gastric acid suppression. The aim of this review was to examine this relationship in further detail. Data from four comparative studies on maintenance PPI therapy for prevention of relapse of RE were combined with data from two pharmacodynamic studies of duration of intragastric pH >4 during the 24-hour period on day 5 of PPI dosing in healthy subjects. A log-linear model was fitted to the data using the method of maximum likelihood. Variability in relapse rates and pH data was taken into account using a binomial and normal likelihood function, respectively. Pharmacodynamic studies resulted in a wide range of acid-suppressive effect, and based on corresponding maintenance of RE healing rates with different PPIs and doses, an inverse (non-linear) statistically significant relationship between percentage of time with pH >4 and maintenance of RE healing was identified (P<0.001). These findings indicate that long-term maintenance of healed RE is related to the extent of acid suppression in a 24-hour period.

Management of Recurrence of Symptoms of Gastroesophageal Reflux Disease: Synergistic Effect of Rebamipide with 15 mg Lansoprazole

Proton pump inhibitors (PPIs) are effective in healing reflux esophagitis and relieving the symptoms of gastroesophageal reflux disease (GERD). Prevention of recurrence of symptoms has become a therapeutic aim in patients with these conditions. We investigated the effects of rebamipide, a mucosal protective anti-ulcer agent, on recurrence of reflux symptoms during PPI maintenance therapy. Patients with esophagitis of Los Angeles classification A or B were treated with PPIs for 8 weeks. Patients with relief of symptoms were enrolled for further study. Forty-one patients were randomized to maintenance therapy with 15 mg of lansoprazole daily or 15 mg of lansoprazole and 300 mg rebamipide daily, and recurrence of symptoms was monitored over 12 months. In some patients, concentration of rebamipide and interleukin(IL)-8 expression in the esophageal mucosa were estimated. During the 12-month period, 11/20 patients (52.4%) taking lansoprazole 15 mg daily suffered recurrence of symptoms, compared to 4/20 patients (20%) treated with lansoprazole 15 mg and rebamipide 300 mg daily (P < 0.05). Rebamipide was detected in the esophageal mucosa 90-180 min after oral administration. IL-8 mRNA expression in the esophageal mucosa of patients with rebamipide was significantly decreased compared with that of patients without rebamipide. Combination therapy with rebamipide and lansoprazole appears to be highly effective in preventing recurrence of symptoms during long-term maintenance treatment for GERD.