PPI Dose Research Articles

Missed Opportunities in the Trial on Proton-Pump Inhibitor Therapy in Bleeding Peptic Ulcers

Letters20 October 2009Missed Opportunities in the Trial on Proton-Pump Inhibitor Therapy in Bleeding Peptic UlcersAlejandro Piscoya, MDAlejandro Piscoya, MDFrom Universidad Peruana de Ciencias Aplicadas, Lima, Peru.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-151-8-200910200-00022 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:I read with interest the article by Sung and colleagues (1). However, it's not news that PPI therapy is better than placebo in the treatment of ulcer bleeding. This was assessed more than a decade ago, and even some cost-effectiveness studies (2) support this conclusion. In addition, some studies (3–5) used low-dose PPI therapy and found no differences between high or low doses of PPI therapy.Is it ethical to continue to use placebo as a control when enough evidence exists that PPI therapy should be used in peptic ulcer bleeding? Perhaps the only new studies on ...

Pretreatment with proton pump inhibitor increases sensitivity of human gastric adenocarcinoma cell line to antitumor drugs

Objective To investigate whether pantoprazole (PPZ), a proton pump inhibitor,could reverse the transmember pH gradient by inhibiting vacuolar H+-ATPase so as to increase the sensitivity of human gastric adenocarcinoma cell line SGC7901 to antitumor drugs and to evaluate the optimal time of drug administration, dosage of PPZ and the possible mechanism. Methods Western blotting and immunofluorescent staining were used to determine the expression and intracellular distribution of vacuolar H+-ATPase in human gastric adenocarcinoma cell line SGC7901 with or without PPZ pretreatment. 2', 7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein, acetoxymethyl ester (BCECF-AM) fluorescent probe was used to measure the intracellular pH value of human gastric adenocarcinoma cell line SGC7901 which pretreated with different dose and time of PPI. Methyl thiazolyl tetrazolium (MTT) assay and annexin V-fluorescent isothiocyanate-propidium iodide double staining were performed to evaluate the cytotoxic effects and apoptosis of cells treated with antitumor drugs combined with PPZ. Adriamycin (ADR) was used as probe to estimate drug accumulation and retention with PPZ pretreatment. Results After 24 hours, the expression of vacuolar H+-ATPase in cells pretreated with PPZ of 10 μg/ml (1.19±0.03) or 100 μg/ml (0. 70±0.03) was significantly lower than that in blank control (1.53±0. 05), but this expression was increased by pretreatment with PPZ of 1 μg/ml (2.29 +0.06, P<0.05). The inhibitory effects of PPZ (10 μg/ml) on vacuolar H+-ATPase was observed at 6 hours (0.32±0.02)and 12 hours (0. 13±0.02). And it could alter the intracellular distribution of vacuolar H+-ATPase at 24-hours. The intracellular pH value in cells pretreated with PPZ of 10 μg/ml (7.44±0. 09 ) or 100 μg/ml (7.31 ± 0. 06) was significantly decreased in comparison with untreated cells (7.51±0.05, P< 0. 01). After administration of anti-tumor drugs, the viability in SGC7901 cells pretreated with PPZ for 24 hours (58.71%±1.18 %) was significantly lower than that in cells untreated with PPZ (74. 33% ± 1.77%, P<0.05), while thetotal and early apoptotic rates in former cells(80.81% ±1. 16% and 77.52 %±1.13 %, respectively) were significantly higher than those in later cells (26. 42%±1.19% and 23. 18% ±0.92%,respectively,P < 0. 01). And the ADR releasing index in cells treated with PPZ (20, 50 and 100 μg/ml) for 24 hours was obviously lower than that in the blank control (0. 164±0. 013, 0. 162±0.015, 0. 152±0. 012 vs 0. 277±0. 011, respectively, P<0. 01). Conclusion The sensitivity of human gastric adenocarcinoma cell line to antitumor drugs may be increased by pretreatment with PPZ. Key words: Vacuolar proton-translocationg ATPases; Pantoprazole; Antineoplastic agents

The Impact of Normalization of Esophageal Acid Profile by Incremental Protein Pump Inhibitors Dosing in Difficult Asthma Patients with Proven Gastro-esophageal Acid Reflux

Background. GER is common in patients with asthma and some, although not all, studies have shown benefit from identification and treatment of GER. Methods. patients with persistent symptoms after optimisation of asthma therapy underwent pH monitoring and adjustment of GER therapy based on the results of repeated pH monitoring. Gastrointestinal symptom scores and asthma therapy requirements were recorded. Results. Over a 2 year period, 51 patients with a definite diagnosis of asthma underwent pH monitoring with GER being identified in 32 (63%). Normal oesophageal acid exposure was achieved in 11 patients, 7 requiring a daily PPI dose greater than 20mg; 8 patients had persisting abnormal oesophageal acid exposure (OAE) despite daily PPI doses up to 80mg. 13 patients declined further pH studies. 8 (73%) patients with normalisation of OAE had meaningful reductions in long term asthma therapy with 2 patients stopping and 2 patients reducing long term oral corticosteroids and 4 others halving the dose of inhaled corticosteroids. No patient who had persisting GER had asthma therapy reduced, neither did any of the group of patients in whom GER was not identified. Conclusion: Tailoring GER therapy with repeated pH studies had a major impact in a subgroup of patients, greater than any other intervention employed in our clinic over the same period. This uncontrolled data adds to the evidence that effective management of GER reduces asthma symptomatology and allows therapy to be reduced in a subgroup of patients with difficult to control asthma.

PPI Dosing Patterns for Recently Bleeding Gastroduodenal Ulcer Disease

Purpose: Studies have demonstrated equivalent healing rates in patients receiving standard (20 mg) versus higher dose omeprazole taken for uncomplicated gastroduodenal ulcer disease (GD). Many experts also recommend standard dose, once daily omeprazole or equivalent for non-acute, recently bleeding GD. We sought to determine PPI dosing patterns for recently bleeding, GD within a single-center, university hospital setting. Methods: Single-center chart review of patients discharged on PPI therapy after endoscopic confirmation of recently bleeding, GD between the years 2003–2007. Inclusion criteria: adults 18–80 years old, acutely or recently bleeding GD confirmed endoscopically, PPI prescribed at hospital discharge. Exclusion criteria: prior h/o GD, h/o GERD/esophagitis, Zollinger-Ellison syndrome, GI malignancy, confirmed or suspected intestinal metaplasia of esophagus, positive/indeterminate H. pylori testing. Ascertainment of PPI type and dose was made from discharge summary or, when unavailable, endoscopy reports. Results: 383, 209 and 57 subjects with recently bleeding gastric, duodenal and dual location ulcers were identified, respectively, over the 5 year study period. Of these, 39, 31 and 10, respectively, met pre-specifed study criteria. 69%, 68% and 100%, respectively, were prescribed PPIs at discharge in excess of standard dosing (see Table). 95% of subjects prescribed PPIs with suprastandard dosing were placed on a twice-daily schedule. Among the entire study cohort, 50% were on NSAIDs, 17% had high-risk stigmata at time of endoscopy. In cases of active bleeding, patients were discharged no sooner than 24 hours from the time of endoscopy. There was no significant trend from year to year in the number of patients receiving PPIs in excess of standard dosing (χ2= 0.61). In the majority of cases no temporal endpoint of therapy was given at the time of PPI prescription. Conclusion: At a university hospital, the majority of patients with recently bleeding GD were discharged on PPI dosages in excess of that generally considered sufficient for ulcer healing. These data build upon the growing recognition of inappropriate PPI usage in a variety of practice settings. A more rational approach to PPI dosing for GD may have many beneficial consequences including significant cost savings.Table

The Endoscopic Plicator Procedure for GERD Using Two Full-Thickness Plications

Purpose: The Plicator® (NDO Surgical, Mansfield MA) endoscopically delivers full-thickness pledgeted sutures to restructure the gastroesophageal junction and the anti-reflux barrier. To date, all Plicator studies have involved the placement of a single, full-thickness suture at the gastro-esophageal junction. The purpose of this pilot study was to evaluate the safety and effectiveness of placing two pledgeted sutures in the anterior gastric cardia. Methods: Patients with symptomatic GERD requiring maintenance proton pump inhibitor therapy were entered in an open-label, prospective, single-center pilot study. Patients with hiatal hernias > 3 cm, grade III and IV esophagitis, and Barrett's esophagus were excluded. All patients received two full-thickness Plicator sutures in the anterior gastric cardia, serially placed within 1 cm of the GEJ. The following were assessed at baseline and 18-months post-treatment: GERD-HRQL, VAS and medication use. The primary study endpoint was ≥50% improvement in GERD-HRQL score. Results: Thirty-seven patients underwent endoscopic full-thickness plication using two sutures. At 18-months post-treatment, the proportion of patients achieving ≥50% improvement in GERD-HRQL score was 57%. Median GERD-HRQL scores improved 61% compared to baseline off-meds scores (12.5 vs. 25.9, P < 0.001) and were superior when compared to patients' baseline on-meds GERD-HRQL scores (12.5 vs.15.6, P= 0.023). Heartburn symptoms measured by VAS showed a median improvement of 77% versus off-med baseline (P < 0.001). Complete PPI cessation was achieved in 35% of patients, with an additional 39% of patients able to reduce their PPI dose by at least half. All procedure-related adverse events occurred acutely, as previously reported, and no new adverse events were observed during extended follow-up. Conclusion: Endoscopic full-thickness plication using two sutures showed in 57% of patients an improvement in GERD-HRQL ≥50% at 18 months. Median GERD-HRQL scores improved 61% and heartburn symptoms showed a median improvement of 77%. Complete PPI cessation was achieved in 35% of patients. No new adverse events were observed during the 18 month follow-up.

Proton‐pump inhibitor failure/resistance: Proposed mechanisms and therapeutic algorithm

AbstractProton‐pump inhibitor (PPI) failure has become more prevalent with the increasing use of PPI as the first‐line agent in the treatment of gastroesophageal reflux disease (GERD). The underlying mechanisms are diverse and may overlap. The commonly available investigations are limited in their capacity in identifying the underlying cause for PPI failure. Multichannel intraluminal impedance with 24‐h pH sensors may be useful to identify non‐acid or duodenogastroesophageal reflux in selected cases. The management strategy for PPI failure is largely empirical. Patients who have symptomatic failure on normal dose of PPI shall try double dose PPI. Failing that, empirical treatment with transient lower esophageal sphincter relaxation reducers or pain modulators can be tried. Better understanding of the pathophysiology and mechanisms for PPI failure will help to improve the management of this rising problem.

Is Intragastric pH Control Maintained over Time on Constant High Dose Proton Pump Inhibitor (PPI)? A Retrospective Pilot Study

Purpose: Relapse of GERD symptoms and erosive esophagitis is seen in a substantial minority of patients on stable long-term doses of PPI. The reason for relapse and the relationship to maintenance of intragastric pH control over time is not known. No study has systematically investigated intragastric pH control in long-term use (over 30 days) of stable doses of PPI (tachyphylaxis?) Aim: To evaluate maintenance of intragastric pH control during long-term steady state PPI therapy. Methods: Retrospective single center database review. Data from dual channel ambulatory pH monitoring (24 hour) performed with pH electrodes 5 cm above the lower esophageal sphincter; and 15 cm below the esophageal electrode and gastric fundus were reviewed. Data from individuals with at least 2 consecutive pH studies on a constant dose of PPI for >28 days were selected. All patients were required to be on 7 days of PPI prior to the pH studies to achieve steady state dosage during testing. Individuals on H2 blocker and PPI, pediatric population, escalating doses of PPI and concurrent motility agent therapy were excluded. Patients were completely de-identified. Upper GI symptoms were recorded at the onset of the pH studies as is standard in our lab. Percent time pH <4 was recorded for upright, supine and total. Difference in mean% time pH <4 was calculated between first and second study. Two tailed paired T tests were calculated (p < 0.05 significant). Results: 17 study patients met inclusion criteria: scleroderma (n) = 11, heartburn (n) = 5, and chest pain (n) = 1. Patients were either taking lansoprazole or omeprazole at least twice daily. Duration of therapy ranged from 2–25 months (mean 10.7). The mean difference in% time gastric pH < 4 increased from study one to two: (15.79%; CI: 1.03 – 30.56; p= 0.038). There was also a trend towards decrease in pH control in the second study for total time pH <4 (mean difference 9.42%; CI 0.92 – 19.78; p= 0.07). There was no significant difference in mean% time gastric pH < 4 upright. Conclusions: This pilot study suggests that there may be a fall off in efficacy of PPI in acid control as assessed by intragastric pH while patients are supine. Whether this represents true “tachyphylaxis” will require a prospective study. The clinical implication of these data remains to be established.

Symptomatic Simultaneous Esophageal, Duodenal, Colonic and Anal Involvement by Amyloidosis

Amyloidosis is a rare progressive disease characterized by abnormal protein deposits in one or more organs. Gastrointestinal (GI) amyloidosis is usually asymptomatic, but may present as malabsorption, pseudo-obstruction, and GI bleeding. We report a patient who uncommonly presented with a variety of GI symptoms related to amyloidosis involving esophagus, stomach, duodenum, colon and anus. Case: A 51-year-old man with multiple myeloma (MM) presented with melena and a Hct of 14. Upper endoscopy showed circumferential erythematous, friable mucosa with diffuse oozing in the distal bulb and second portion of duodenum. Hemostasis was achieved by injection of epinephrine. He also had perianal discomfort and bleeding, exam revealed a large verrucous plaque on the left side of the anus extending to perineum. Patient was treated with high doses of PPI. 10 days later the patient returned to hospital complaining of intermittent melena and recent bright red blood per rectum. Repeat endoscopy showed an antral ulcer, inflamed, friable mucosa in duodenum with narrowing, and no active bleeding. Colonoscopy showed erythema, edema and friable mucosa with oozing in the sigmoid colon. All sites including the anal lesion were biopsied. Histopathology demonstrated squamous hyperplasia with dermal amyloid deposits in the anal lesion. The gastric, duodenal and colon biopsies also showed amyloid deposit. Within 2 weeks he developed rapidly progressive dysphagia, inability to maintain oral intake and weight loss. Endoscopy showed no inflammation, ulcer or stricture formation in esophagus. Esophageal biopsy showed amyloid deposit in the mucosa. Speech was normal and he was able to initiate a swallow. The patient underwent a jejunostomy tube placement for feeding. Discussion: This case demonstrates rare symptomatic involvement of almost the entire GI tract with amyloidosis causing upper and lower GI bleeding, dysphagia and a perianal lesion masquerading as squamous cell carcinoma. Esophageal involvement with rapid onset of severe dysphagia requiring J-tube placement is very unusual and represents a motor disorder of the esophagus. Condylomatous cutaneous amyloidosis has been reported, but most of the time well after the diagnosis of amyloidosis has been made. Our case demonstrates the importance of considering GI amyloidosis in the differential diagnosis of a variety of GI symptoms.

Endoscopic Injection of Durasphere for the Treatment of GERD - Long Term Human Pilot Study

Background: Endoscopic treatment of gastroesophageal reflux (GERD) remains suboptimal. The ideal endoscopic therapy for GERD should be safe, efficacious, durable, and easy to perform with minimal discomfort. The aim of this study was to demonstrate the feasibility, safety, and antireflux efficacy of submucosal augmentation, at or just below the squamocolumnar junction, with a biocompatible, nonmigratory, nonabsorbable pyrolytic carbon-coated bead suspension (Durasphere®. Methods: Ten GERD patients (mean age 40), with heartburn symptoms responsive to PPI use were enrolled. Clinical assessment included: endoscopy, esophageal manometry, Bravo pH monitoring, heartburn diary, and GERD-HRQL severity scoring at baseline, 3, 6, and 12 months. The procedure was performed in an outpatient endoscopy clinic using conscious sedation. Durasphere® was injected into the submucosal space, using a sclerotherapy catheter in two sets of 1-2 cc four quadrant injections, at and just below the squamocolumnar junction. The mean initial injection volume of Durasphere was 8.6 (4.7-13.9) mls. 3 patients who experienced incomplete symptom relief were reinjected. Outcome measures included PPI use, change in GERD-HRQL symptom scores, change in Bravo pH scores, and adverse events. Results: 12 month data is pending. At 6 months, 80% of patients had reduced their PPI dose by ≥50% compared to baseline, and 70% eliminated PPI use entirely (p < .001). The mean GERD-HRQL symptom score was 26.9 at baseline (off PPI) and 9.1 at follow-up - a 66% reduction (p < .002). Bravo pH results were available on eight patients. The mean percent total time with pH ≤ 4 for these patients was 14.2 at baseline and 9.9 following injection, a 30% reduction (p < .066). Symptomatic reflux episodes improved from an average of 46.7 at baseline to 6.6 episodes at follow-up - a reduction of 86% (p < .011). 3 of 8 patients normalized their DeMeester score. There were no serious adverse events. Transient (<12 hours) mild epigastric discomfort was reported by 60% of the patients but did not require analgesia. There was no dysphagia, and all patients resumed a regular diet within a few hours of the procedure. The technique was rated as “simple” by the endoscopist. Conclusions: Endoscopic injection of Durasphere into the submucosal space, at the GE junction, is a feasible, new method for the treatment of GERD. This preliminary clinical study has shown that Durasphere is technically simple, has excellent short-term efficacy and can be safely performed in an outpatient endoscopy clinic. Further study of this technique, evaluating a larger number of patients in the setting of a 1 year controlled trial is warranted.

Inappropriate Use of Intravenous Pantoprazole: Extent of the Problem and Successful Solutions

Indications for intravenous proton pump inhibitors (IV PPI) include upper gastrointestinal bleeding (UGIB) from peptic ulcer disease with high-risk stigmata and patients receiving nothing by mouth (NPO). The objectives were to assess the extent of errors in indications for IV PPI use and to determine whether multidisciplinary interventions could improve IV PPI use and costs. Part 1: Patients prescribed IV PPI during a period of 4 months were divided into 2 settings, UGIB or non-UGIB. The setting-specific appropriateness of the IV PPI indication and dosing regimen was determined. Part 2: Patients prescribed IV PPI before and after multidisciplinary interventions (educating physicians, a computerized dose template, pharmacists altering IV PPI orders in non-UGIB patients who were not NPO, and recommending a GI consult when a continuous infusion was ordered) were studied. Incidence of prescribing errors, IV PPI costs, and potential confounders were compared. Part 1: Only 50% of UGIB (n = 145) patients received IV PPI for an appropriate indication. Both indication and dosing regimen were appropriate in 21%. In the non-UGIB group (n = 95), 33% were truly NPO; 51% had a correct dosing frequency. Part 2: The postintervention (n = 105) group (vs the preintervention group, n = 113) showed a significant absolute reduction in the degree of inappropriate indication in the UGIB (26%; 95% confidence interval [CI], 10%-42%; P < .0001) and in the non-UGIB (41%; 95% CI, 24%-58%; P < .0001) subgroups. However, a greater improvement in underspending than overspending meant that overall costs were unchanged. IV PPI was frequently prescribed inappropriately and incorrectly; simple maneuvers resulted in reductions in errors.

A Randomized Controlled Trial of Ablation of Barrett’s Esophagus With Electrocautery vs. Argon Plasma Coagulation: Long-Term Results

Background: Many modalities have been used to ablate Barrett’s esophagus (BE) including multipolar electrocoagulation (MPEC), argon plasma coagulation (APC), laser, heater probe, etc. However, long-term results and comparative effectiveness are not known. Aim: Our aim was to compare efficacy of achieving complete reversal (ie, endoscopic and histologic) between MPEC and APC in BE patients. Methods: Patients with BE, 2–6 cm long underwent 24-hour pH test on PPI therapy (rabeprazole 20 mg BID). Twenty-four-hour pH was performed by placing probe 5-cm above LES, after at least 7 days of PPI therapy. Patients were then randomized by BE length to undergo ablation with either MPEC or APC every 4–8 weeks till endoscopic reversal or maximum of 6 treatment sessions. If the patient developed reflux symptoms or had documented erosive esophagitis, PPI dose was increased. To document BE reversal, esophagus was sprayed with Lugol’s solution, and 4 quadrant jumbo biopsies every 2 cm were obtained. Biopsies were stained with H&E/alcian blue to detect residual intestinal metaplasia. Fisher’s exact test and logistic regression were done to study effect of BE length, pH scores, hernia size, PPI dose, and ablation modality in achieving BE reversal. Results: Thirty-five BE patients have been followed-up for at least 2 years after endoscopic ablation, 16 treated with MPEC, and 19 with APC. Mean age was 61 years (32–84 years), 34 males. Mean length of BE was 3.7 ± 1.7 cm. Median total time pH <4 was 0.6% (range 0–29.9%); median upright and supine values were 0.7% and 0% respectively. Acid exposure normalized in 26 patients (74%) on rabeprazole 20 mg BID. BE completely reversed in 24 patients (69%); 75% with MPEC, and 63% with APC (P = .49). Mean number of sessions required was 3.8 in MPEC and 3.4 in APC group (P = .48). There was no significant difference in either treatment type (MPEC vs. APC), pH results, BE length, PPI dose, or hernia size between patients with and without complete reversal. No GI bleed or perforations noted; one patient developed an esophageal stricture treated successfully with 1 dilation. Conclusions: In BE patients treated with MPEC or APC in combination with aggressive acid suppression, there are no significant predictors associated with achieving complete reversal of BE including BE length, 24-hour pH, hiatus hernia size, and PPI dose. At long-term follow-up (2 years), complete reversal of BE can be maintained in ∼ 70% of patients irrespective of technique, ie, MPEC vs. APC. Continued surveillance is still indicated in post-ablative setting.

A Prospective Single Center Long-Term Follow up Study of Barrettʼs Esophagus on Proton Pump Inhibitor Therapy

Purpose: The aim of this study was to evaluate the esophageal and gastric findings in patients with Barrett's esophagus on long term PPI therapy in our center Methods: 61 patients with biopsy proven Barrett's esophagus on continuous PPI therapy have been followed as follows: 2 for 16 years, 18 for 15 years, 30 for 14 years, 2 for 13 years, 6 for 12 years, 3 for 11 years. Initially omeprazole was used on alternate days because of the “black box” warning. Thereafter, 53 patients are maintained on a daily dose of PPI (Omeprazole 20 mg or esomeprazole 40 mg twice daily in 27 patients and once daily in 26 patients). 8 patients remained on an alternate day regime. Surveillance endoscopies (3 months to 2 years) with esophageal and gastric biopsies have been performed in all. Results: Non-Esophagogatric Events: 7 patients (11.5%) have died from non-esophagogastric causes and 17 (28%) have developed unrelated diseases. Esophagogastric Findings: Esophageal- one patient with once daily dose of PPI developed high grade dysplasia (1.7%) after 5 years of follow up, but refused surgery and has remained on endoscopic follow up. Another patient had low grade dysplasia on biopsy, remained on twice daily PPI and repeat biopsies are consistently negative for dysplasia. 4 patients had recurrent grade B or C esophagitis that responded to an increased dose of PPI. Gastric −20 patients (30%) developed gastric fundic polyps (2 to more than 100) after more than 2 years of PPI therapy. One patient developed a large (3 × 3 cm) adenomatous polyp with severe dysplasia requiring endoscopic resection and follow up did not show recurrence. Conclusions: A single center 12–15 year (cumulative 853 person-years) prospective follow up of patients with Barrett's esophagus on continuous PPI therapy revealed very low incidence of dysplasia (one case) and no carcinoma. Gastric polyps are common on PPI therapy and one patient had high grade dysplastic gastric adenoma. The high mortality and morbidity (39.5% in this group) from unrelated causes in patients with Barrett's esophagus favour a conservative approach; however, continued surveillance of both esophageal and gastric status would seem prudent on long term PPI therapy.

A Randomized Controlled Trial of Ablation of Barrett's Esophagus With Electrocautery Vs. Argon Plasma Coagulation: Long Term Results

Many modalities have been used to ablate Barrett's esophagus (BE) including multipolar electrocoagulation(MPEC), argon plasma coagulation(APC), laser, heater probe, etc. However, long term results and comparative effectiveness are not known. Aim: Our aim was to compare efficacy of achieving complete reversal (i.e. endoscopic and histologic) between MPEC and APC in BE pts. Methods: Pts with BE, 2-6 cm long underwent 24 hr pH test on PPI therapy (rabeprazole 20 mg BID). 24 h pH was performed by placing probe 5 cm above LES, after at least 7 days of PPI therapy. Pts were then randomized by BE length to undergo ablation with either MPEC or APC every 4-8 weeks till endoscopic reversal or maximal of 6 treatment sessions. If pt developed reflux symptoms or had documented erosive esophagitis, PPI dose was increased. To document BE reversal, esophagus was sprayed with Lugol's solution and 4 quadrant jumbo biopsies every 2 cm were obtained. Biopsies were stained with H & E/alcian blue to detect residual intestinal metaplasia. Fisher's Exact test and logistic regression were done to study effect of BE length, pH scores, hernia size, PPI dose & ablation modality in achieving BE reversal. Results: 35 BE pts. have been followed for at least 2 yrs after endoscopic ablation, 16 treated with MPEC and 19 with APC. Mean age was 61 yrs (32-84 years), 34 males. Mean length of BE was 3.7 +/− 1.7 cm. Median total time pH <4 was 0.6% (range 0-29.9%); median upright & supine values were 0.7% and 0% respectively. Acid exposure normalized in 26 pts (74%) on rabeprazole 20mg BID. BE completely reversed in 24 pts (69%); 75% with MPEC and 63% with APC (p = 0.49). Mean no. of sessions required was 3.8 in MPEC and 3.4 in APC group (p = 0.48). There was no significant difference in either treatment type (MPEC vs. APC), pH results, BE length, PPI dose or hernia size between pts with and without complete reversal. No GI bleed or perforations noted; one pt developed an esophageal stricture treated successfully with 1 dilation. Conclusions: In BE pts. treated with MPEC or APC in combination with aggressive acid suppression, there are no significant predictors associated with achieving complete reversal of BE including BE length, 24 hr pH, hiatus hernia size and PPI dose. At long term f/u (2yrs), complete reversal of BE can be maintained in ~ 70% of pts irrespective of technique i.e. MPEC vs. APC. Continued surveillance is still indicated in post ablative setting. Funded by Eisai/Janssen.

The Plicator Procedure for the Treatment of GERD: 12-Month Multicenter Results

Background: The Plicator (NDO Surgical Inc., Mansfield, MA) is a unique endoscopic suturing device which delivers a transmural suture. The ability to achieve serosal tissue apposition allows for restructuring of the cardia and reshaping of the valvular mechanism at the gastro-esophageal junction (GEJ). Aim: To assess the safety and 12-month efficacy of endoscopic full-thickness suturing using a second generation, reduced diameter Plicator. Methods: Thirty-six patients with chronic heartburn requiring maintenance anti-secretory therapy received a single, endoscopically placed, full-thickness plication in the gastric cardia 1 cm below the GEJ. Study exclusions included hiatal hernia >2 cm, Grades III and IV esophagitis, and Barrett's esophagus. At baseline and 12-months post-plication, patients were evaluated for GERD symptoms and medication use. Ambulatory 24-hr pH studies were conducted at baseline and repeated between 6 and 12-months post-plication. Results: Thirty-six patients underwent endoscopic full-thickness plication with two patients lost to follow-up. There were no serious adverse events. Common side effects included sore throat (23%) and epigastric pain (21%) which resolved spontaneously. Two patients were admitted overnight for observation. One year post-plication, 68% (23/34) of PPI dependent patients remained off daily PPI therapy; with an additional 12% (4/34) able to reduce their PPI dose by at least 50%. Median GERD-HRQL scores were significantly improved versus baseline off-meds (16.0 vs. 7.0) and were comparable to baseline on-meds values (7.0 vs. 5.0). Twenty-six subjects underwent post-procedure ambulatory pH studies (mean follow-up 9.5 months). Of these, 73% demonstrated an improvement in distal esophageal acid exposure. Median % time pH<4 decreased 29% (9.9 to 8.1) with 23% of patients experiencing pH normalization. Conclusions: Endoscopic full-thickness suturing with the reduced diameter Plicator was found to be a safe procedure that can effectively reduce symptoms, medication use and esophageal acid exposure associated with GERD. Background: The Plicator (NDO Surgical Inc., Mansfield, MA) is a unique endoscopic suturing device which delivers a transmural suture. The ability to achieve serosal tissue apposition allows for restructuring of the cardia and reshaping of the valvular mechanism at the gastro-esophageal junction (GEJ). Aim: To assess the safety and 12-month efficacy of endoscopic full-thickness suturing using a second generation, reduced diameter Plicator. Methods: Thirty-six patients with chronic heartburn requiring maintenance anti-secretory therapy received a single, endoscopically placed, full-thickness plication in the gastric cardia 1 cm below the GEJ. Study exclusions included hiatal hernia >2 cm, Grades III and IV esophagitis, and Barrett's esophagus. At baseline and 12-months post-plication, patients were evaluated for GERD symptoms and medication use. Ambulatory 24-hr pH studies were conducted at baseline and repeated between 6 and 12-months post-plication. Results: Thirty-six patients underwent endoscopic full-thickness plication with two patients lost to follow-up. There were no serious adverse events. Common side effects included sore throat (23%) and epigastric pain (21%) which resolved spontaneously. Two patients were admitted overnight for observation. One year post-plication, 68% (23/34) of PPI dependent patients remained off daily PPI therapy; with an additional 12% (4/34) able to reduce their PPI dose by at least 50%. Median GERD-HRQL scores were significantly improved versus baseline off-meds (16.0 vs. 7.0) and were comparable to baseline on-meds values (7.0 vs. 5.0). Twenty-six subjects underwent post-procedure ambulatory pH studies (mean follow-up 9.5 months). Of these, 73% demonstrated an improvement in distal esophageal acid exposure. Median % time pH<4 decreased 29% (9.9 to 8.1) with 23% of patients experiencing pH normalization. Conclusions: Endoscopic full-thickness suturing with the reduced diameter Plicator was found to be a safe procedure that can effectively reduce symptoms, medication use and esophageal acid exposure associated with GERD.

The Influence of H pylori Infection on the Healing Process of Gastric Ulcers After Endoscopic Submucosal Dissection

Background & Aim: FEndoscopic submucosal dissection (ESD) is rapidly becoming popular for treatment of mucosal tumors in the GI tract, especially for larger lesions difficult for conventional EMR. We have previously reported that gastric artificial ulcers after ESD would heal within 8 weeks regardless of size and its location, if there is no preoperative fibrosis under the lesion. In this study, we examined the influence of Helicobacter Pylori (HP) infection on the healing process of gastric ulcers after ESD. Method: From 2000 to 2003, 79 patients (male 65, female 14) who underwent ESD for mucosal tumors, and of which infectious state of HP was confirmed either pathologically or serologically, were included. The healing stage, pattern of scar formation was studied at follow up endoscopy performed within 6 to 8 weeks after the treatment. Normal doses of PPI and sucralfate were given for 8 weeks for postoperative medication. In addition, patients whose serum pepsinogen (PG) was evaluated before treatment (66 patients), were divided in 3 groups; PG positive (PG I < 70 and I/II < 3), strongly positive (PG < 30 and I/II < 2) and negative, according to Miki et al, to study the influence of atrophic gastritis on ulcer healing. Result: The average specimen size removed by ESD was 34 mm (range 20 to 90 mm). In 60 cases (76%), the ulcer contracted in the short axis (axial direction) of the stomach, resulting in linear scars along the long axis (sagittal direction). In 19 cases (24%), the ulcer contracted nearly in a concentric form, resulting in an asteroid scar. In 5 patients, a small mucosal defect was still observed at follow up, of which ulcerative findings were present before treatment. Infection of HP was positive in 68 patients, negative in 11 patients (previously eradicated 3, negative with atrophic gastritis 7, negative without atrophic gastritis 1). There were no significant difference in the healing stage or scar formation regarding HP infection state. Patients of PG positive, strongly positive and negative were 36, 15 and 15 patients, respectively. There were no significant difference among the 3 groups. Conclusion: Infection of HP or the degree of atrophic gastritis have no influence on the healing process of gastric ulcers after ESD.

Three year’s experience with the Stretta procedure: did it really make a difference?

Endoscopic treatment is merging as a new option for GERD treatment. Many modalities have been used with modest short-term success, but no long-term follow-ups have been published. We present our 3-yr experience at Vanderbilt University using endoscopic radiofrequency energy (Stretta procedure) for GERD treatment. Patients with follow-up >6 months were prospectively studied under IRB protocol. All were mailed SF-12 health status questionnaire and GERD specific quality-of-life (QOLRAD) questionnaires, queries about satisfaction with Stretta, and medication use. All were invited for 24-hour pH study. Eighty-six Stretta procedures were performed between 8/2000 and 7/2003 on 85 patients; all were outpatients, 89% under conscious sedation. Seventy-seven patients qualified for the study; 61 completed the survey, 24 returned for pH study. Follow-up was 26.2 +/- 7.5 months (6-36). All were on daily PPIs, with proven GERD by pH study or endoscopy. Mean preoperative acid exposure time was 7.8+/-2.6%, mean DeMeester score was 40.2+/-17.6. Postoperative mean acid exposure time was 5.1+/-3.3 (p=0.001), DeMeester score was 29.5+/-20.5 (p=0.041). Normal postoperative acid exposure time (pH<4 in <4.2%) was achieved in 42% of patients tested. Patients were then divided according to medication use at the end of f/u in 2 groups: Responders (off or >50% decrease in PPI dose), and nonresponders (on >50% of original PPI dose, or had fundoplication). Response rate was 60% (39 patients), 8 nonresponders underwent fundoplication (12%). Satisfaction rate was 73%. Statistically significant difference was found between the 2 groups in all measurements; SF-12 physical and mental score for responders were 45.5+/-10.2, and 52.6+/-7.8; and for nonresponders were 37.8+/-11.2 and 40.9+/-11.3 (p=0.012, p=0.0001), respectively. Statistically significant difference was also found between responders and nonresponders in postoperative acid exposure (4.5+/-3.34 vs 7.2+/-2.3, p=0.034), and DeMeester score (26.3+/-20.4 vs 39.7+/-20.2, p=0.05). Paired T test was used to compare pre- and postoperative acid exposure in each group; statistically significant difference was found only among responders: total reflux time was 7.50+/-2.3 preop and 4.5+/-3.34 postop (p=0.0001), whereas for nonresponders it was 8.6+/-3.7 and 7.2+/-2.3 (p=0.8), DeMeester scores pre- and postop among responders were 40.0+/-19.7 and 26.3+/-20.4, respectively (p=0.016), whereas for nonresponders it was 40.5+/-14.3 and 39.7+/-20.2 (p=0.79). Stretta is a safe modestly effective, totally endoscopic treatment for GERD. Symptomatic improvement when achieved is often associated with correlating improvement in distal acid exposure. This exposure normalizes in nearly half the treated patients.

DIFFERENCES IN PROTON PUMP INHIBITOR PRESCRIPTIVE ACTIVITY AMONGST ELDERLY OUTPATIENT VETERAN PATIENTS

Purpose: The frequency of multiple dosing of protonpump inhibitors (PPI's) is not well established in the US. With the availability of several agents in this class of drugs, we sought to study the prescribing patterns of 14,473 outpatients given either lansoprazole or rabeprazole. While comparisons on dose and frequency have been made before, however, duration of treatment, race of patients studied and age patient populations being prescribed these PPI's has not been well studied due to the restrictive data sets of pharmacy based information Methods: Outpatients prescribed one of two formulary proton pump inhibitors (lansoprazole, rabeprazole) were identified retrospectively from the Cleveland-area Veteran's hospitals. Patient information collected included age, race, sex, dose, duration of prescription, and frequency. Data was collected and analyzed Results: We found significant differences in the prescriptive activity in the two proton pump inhibitors studied. Patients receiving Lansoprazole received significantly more tablets than patients treated with Rabeprazole for 30 and 60 days of treatment. More Rabeprazole was used for treatement lasting 90 days and beyond. As well, younger patients received higher doses of PPI's, compared to older patients. For patients treated with Lansoprazole, the mean age of all patients was 65.4 years. Individuals less than 65 years of age had an average 35 mg per day dose whereas those greater than 65 years of age had an average dose of 32.6 mg (p = 1.53×10-8). Similarly, for patients treated with rabeprazole, the mean age was 66.14 years, patients aged less than 65 recieved 23.27 mg and overage 65 recieved 22.82 mg (p = 1.69 × 10–3). Black patients also received increased doses of PPI's compared to the White and Asian patients Conclusions: The differences in prescriptive activities between the groups studied at the Cleveland Veteran's administration supports different uses by practitioners using either Lansoprazole or Rabeprazole. Elderly patients in particular recieved significantly less PPI than younger patients.

WIRELESS PH-METRY COMBINED WITH SURVEILLANCE ENDOSCOPY IN BARRETTʼS ESOPHAGUS

Purpose: Recent evidence indicates that normalization of esophageal acid exposure in Barrett's esophagus (BE) may reduce the risk of neoplasia. The aims of this study were (1) assess the adequacy of PPI therapy on esophageal acid exposure in patients with BE, and (2) evaluate the safety and patient tolerance of wireless pH-metry performed in conjunction with surveillance endoscopy and biopsy. Methods: We enrolled 30 patients with BE presenting for surveillance endoscopy. Subjects maintained their usual dose of PPI. The EGD and biopsies were completed according to protocol. A wireless pH capsule (Bravo pH System) was placed immediately following EGD. All pts completed an 8-question satisfaction survey using a 6-point scale for each response (6 = best). Results: The combined procedures were successful in all 30 cases. Sixteen patients (53%) were on once daily (QD) PPI and 14 (47%) were on twice daily (BID) PPI. Fourteen patients had reflux symptoms on therapy. The mean length for BE was 3.3 cm and the mean disease duration 4.8 yrs. An average of 6.4 biopsies was performed per EGD. The % time pH <4 [median (interquartile range)] was 8.4% (11.5), 6.9% (9.4), and 13.2% (18.5) for total, upright and supine time. Esophageal acid exposure was similar in patients with and without GERD symptoms. Normalization of esophageal acid exposure is reported in Table. Ratings from the post-procedural survey demonstrated: satisfaction with the procedure (5.8), ability to carry on usual activities during pH-metry (5.6), and overall assessment of the experience (4.9).TableConclusions: In pts with BE (1) PPI therapy fails to control esophageal acid exposure in 44–57% of patients, (2) the absence of GERD symptoms during PPI therapy does not predict normalization of esophageal acid exposure, and (3) wireless pH-metry is safe and well-tolerated when performed in conjunction with surveillance EGD.

H. pylori eradication increases intragastric acidity during PPI dosing

H. pylori eradication increases intragastric acidity during PPI dosing

Replacement of oral proton pump inhibitors with intravenous pantoprazole to effectively control gastric acid hypersecretion in patients with Zollinger-Ellison syndrome.

In patients with Zollinger-Ellison syndrome (ZES) or other conditions requiring oral doses of proton pump inhibitors, it frequently becomes necessary to use parenterally administered gastric acid inhibitors. However, i.v. histamine-2 receptor antagonists are not effective at usual doses and lose their effectiveness because of tachyphlaxis. With the approval in the United States of i.v. pantoprazole, a substituted benzimidazole available in i.v. formulation, it will become possible to acutely manage gastric acid secretion in the acute care setting of a hospital. This study was developed to monitor the safety and establish the efficacy of i.v. pantoprazole as an alternative to oral proton pump inhibitors for the control of gastric acid hypersecretion in patients with ZES. The efficacy of replacing oral PPI therapy with i.v. pantoprazole was evaluated in 14 ZES patients. After study enrollment, patients taking their current doses of oral PPI (omeprazole or lansoprazole) were switched to pantoprazole i.v. for 6 days during an 8-day inpatient period in the clinical research center. Effective control was defined as an acid output (AO) of < 10 mEq/h (< 5 mEq/h in patients with prior gastric acid-reducing surgery). The mean age of the 14 patients enrolled in the study was 52.4 yr (range = 38-67). Mean basal AO was 0.55 +/- 0.32 mEq/h and mean fasting gastrin was 1089 pg/ml (range = 36-3720). Four patients were also diagnosed with the multiple endocrine neoplasia type I syndrome, nine were male, and two had previously undergone acid-reducing surgery. Before study enrollment, gastric acid hypersecretion was controlled in nine of 14 patients with omeprazole (20-200 mg daily) and five of 14 with lansoprazole (30-210 mg daily). In the oral phase of the study all patients had adequate control of gastric acid secretion, with a mean AO of 0.55 +/- 0.32 mEq/h (mean +/- SEM). Thereafter, 80 mg of i.v. pantoprazole was administered b.i.d. for 7 days by a brief (15 min) infusion and the dose was titrated upward to a predetermined maximum of 240 mg/24 h to control AO. A dose of 80 mg b.i.d. of i.v. pantoprazole controlled AO in 13 of 14 of the patients (93%) for the duration of the study (p > 0.05 compared to baseline values for all timepoints). One sporadic ZES patient (oral control value = 0.65 mEq/h on 100 mg of omeprazole b.i.d. p.o.) was not controlled with 80 mg of i.v. pantoprazole b.i.d. and dosage was titrated upward to 120 mg b.i.d. after day 2. There were no serious adverse events observed. Intravenous pantoprazole provides gastric acid secretory control that is equivalent to the acid suppression observed with oral proton pump inhibitors. Most ZES patients (93%) maintained effective control of AO previously established with oral PPIs when switched to 80 mg of i.v. pantoprazole b.i.d.; however, for difficult-to-control patients, doses > 80 mg b.i.d. may be required.