Proton Pump Inhibitor Consumption Research Articles

Hiatal Hernia Repair With Tension-Free Mesh or Crural Sutures Alone in Antireflux Surgery

Antireflux surgery is an effective treatment of gastroesophageal reflux disease (GERD), but the durability of concomitant hiatal hernia repair remains challenging. Previous research reported that the use of a mesh-reinforced, tension-free technique was associated with more dysphagia for solid foods after 3 years without reducing hiatal hernia recurrence rates compared with crural sutures alone, but the long-term effects of this technique have not been assessed. To assess the long-term anatomical and functional outcomes of using a mesh for hiatal hernia repair in patients with GERD. A double-blind, randomized clinical trial was performed at a single center (Ersta Hospital, Stockholm, Sweden) from January 11, 2006, to December 1, 2010. A total of 159 patients were recruited and randomly assigned. Data for the current analysis were collected from September 1, 2021, to March 31, 2022. All analyses were conducted with the intention-to-treat population. Closure of the diaphragmatic hiatus with crural sutures alone vs a tension-free technique using a nonabsorbable polytetrafluoroethylene mesh (Bard CruraSoft). The primary outcome was radiologically verified recurrent hiatal hernia after more than 10 years. Secondary outcomes were dysphagia scores (ranging from 1 to 4, with 1 indicating no episodes of dysphagia and 4 indicating more than 3 episodes of dysphagia per day) for solid and liquid foods, generic 36-Item Short Form Health Survey and disease-specific Gastrointestinal Symptom Rating Scale symptom assessment scores, proton pump inhibitor consumption, and reoperation rates. Intergroup comparisons of parametric data were performed using t tests; for nonparametric data, Mann-Whitney U, χ2, or Fisher exact tests were used. For intragroup comparisons vs the baseline at follow-up times, the Friedman test was used, and post hoc analysis was performed using Wilcoxon matched pairs. Of 145 available patients, follow-up data were obtained from 103 (response rate 71%; mean [SD] age at follow-up, 65 [11.3] years; 55 [53%] female), with 53 initially randomly assigned to mesh reinforcement, and 50 to crural suture alone. The mean (SD) follow-up time was 13 (1.1) years. The verified radiologic hiatal hernia recurrence rates were 11 of 29 (38%) in the mesh group vs 11 of 35 (31%) in the suture group (P = .61). However, 13 years postoperatively, mean (SD) dysphagia scores for solids remained significantly higher in the mesh group (mean [SD], 1.9 [0.7] vs 1.6 [0.9]; P = .01). Findings from this long-term follow-up of a randomized clinical trial suggest that tension-free crural repair with nonabsorbable mesh does not reduce the incidence of hiatal hernia recurrence 13 years postoperatively. This finding combined with maintained higher dysphagia scores does not support the routine use of tension-free polytetrafluoroethylene mesh closure in laparoscopic hiatal hernia repair for treatment of GERD. ClinicalTrials.gov Identifier: NCT05069493.

The long-term efficacy of transoral incisionless fundoplication with Medigus Ultrasonic Surgical Endostapler (MUSE) for gastroesophageal reflux disease

BackgroundTo evaluate the long-term efficacy of transoral incisionless fundoplication (TIF) with Medigus Ultrasonic Surgical Endostapler (MUSE) for gastroesophageal reflux disease (GERD).MethodsA total of 16 patients with proton pump inhibitor-dependent gastroesophageal reflux disease had undergone TIF by MUSE in Shanghai General Hospital （Shanghai, China）from March 2017 to December 2018. Patients were followed up at 6 months, and the GERD-health-related quality of life (GERD-HRQL) questionnaire score, the GERD questionnaire (GERD-Q) score, high-resolution esophageal manometry (HREM) and 24 h esophageal pH parameters, the Hill grade of the gastroesophageal flap valve (GEFV) and daily Proton pump inhibitor (PPI) consumption before and after procedure were compared. Patients also were followed up at 3 years and 5 years using a structured questionnaire via phone which evaluated symptoms of reflux, dose of PPI medication and side effects.ResultsFollow-up data were collected from 13 patients, ranging from 38 to 63 months, 53 months on average. 10/13 patients reported symptomatic improvement and daily PPI consumption was stopped or halved in 11/13. After procedure, the mean scores of GERD-HRQL and GERD-Q were significantly increased. The mean DeMeester score, the mean acid exposure time percentage and the mean number of acid reflux episodes were significantly lower. The mean rest pressure at lower esophageal sphincter (LES) had no significant difference.ConclusionTIF by MUSE has significant efficacy in the treatment of PPI-dependent GERD, which can improve symptoms and life quality of patients, and reduce the acid exposure time for long-term. Chictr.org.cn.Trial RegistrationChiCTR2000034350.

Does Chronic Use of High Dose Proton Pump Inhibitors Increase Risk for Pancreatic Cancer?

To analyze whether use of proton pump inhibitors increase the risk for pancreatic cancer in a mouse model and human clinical cohorts. p48-Cre/LSL-KrasG12D mice that develop precancerous pancreatic intraepithelial neoplasia (PanINs) were treated with low- or high-dose proton pump inhibitors (PPIs) orally for 1 and 4 months. The mechanism for the cholecystokinin receptor 2 (CCK-2R) activation was investigated in vitro. Two resources were employed to analyze the risk of pancreatic cancer in human subjects with PPI use. Serum gastrin levels were increased 8-fold (P < 0.0001) in mice treated with chronic high-dose PPIs, and this change correlated with an increase (P = 0.02) in PanIN grade and the development of microinvasive cancer. The CCK-2R expression was regulated by microRNA-148a in the p48-Cre/LSL-KrasG12D mice pancreas and in human pancreatic cancer cells in vitro. Proton pump inhibitor consumption in human subjects was correlated with pancreatic cancer risk (odds ratio, 1.54). A validation analysis conducted using the large-scale United Kingdom Biobank database confirmed the correlation (odds ratio, 1.9; P = 0.00761) of pancreatic cancer risk with PPI exposure. This investigation revealed in both murine models and human subjects, PPI use is correlated with a risk for development of pancreatic cancer.

Clinical Outcomes of a Laparoscopic Total vs a 270° Posterior Partial Fundoplication in Chronic Gastroesophageal Reflux Disease

The efficacy of fundoplication operations in the management of gastroesophageal reflux disease (GERD) has been documented. However, few prospective, controlled series report long-term (>10 years) efficacy and postfundoplication concerns, particularly when comparing various types of fundoplication. To compare long-term (>15 years) results regarding mechanical complications, reflux control, and quality of life between patients undergoing posterior partial fundoplication (PF) or total fundoplication (TF) (270° vs 360°) in surgical treatment for GERD. A double-blind randomized clinical trial was performed at a single center (Ersta Hospital, Stockholm, Sweden) from November 19, 2001, to January 24, 2006. A total of 456 patients were recruited and randomized. Data for this analysis were collected from August 1, 2019, to January 31, 2021. Laparoscopic 270° posterior PF vs 360° TF. The main outcome was dysphagia scores for solid and liquid food items after more than 15 years. Generic (36-Item Short-Form Health Survey) and disease-specific (Gastrointestinal Symptom Rating Scale) quality of life and proton pump inhibitor consumption were also assessed. Among 407 available patients, relevant data were obtained from 310 (response rate, 76%; mean [SD] age, 66 [11.2] years; 184 [59%] men). A total of 159 were allocated to a PF and 151 to a TF. The mean (SD) follow-up time was 16 (1.3) years. At 15 years after surgery, mean (SD) dysphagia scores were low for both liquids (PF, 1.2 [0.5]; TF, 1.2 [0.5]; P = .58) and solids (PF, 1.3 [0.6]; TF, 1.3 [0.5]; P = .97), without statistically significant differences between the groups. Reflux symptoms were equally well controlled by the 2 types of fundoplications as were the improvements of quality-of-life scores. The long-term findings of this randomized clinical trial indicate that PF and TF are equally effective for controlling GERD and quality of life in the long term. Although PF was superior in the first years after surgery in terms of less dysphagia recorded, this difference did not prevail when assessed a decade later. ClinicalTrials.gov Identifier: NCT04182178.

Transoral incisionless fundoplication with Medigus ultrasonic surgical endostapler (MUSE) for the treatment of gastro-esophageal reflux disease: outcomes up to 3years.

Transoral incisionless fundoplication (TIF) with Medigus Ultrasonic Surgical Endostapler (MUSE) is a new intervention for treatment of gastro-esophageal reflux disease (GERD). We aimed at assessing the clinical, functional, and endoscopic effects of TIF by MUSE. Forty-six patients underwent TIF. Proton pump inhibitor (PPI) consumption, GERD-health-related quality of life (HRQL) and reflux symptom index (RSI) questionnaires, upper gastrointestinal (GI) endoscopy, esophageal 24-h pH-impedance recording, and high-resolution manometry (HRM) were done before TIF and scheduled 6 and 12months later (HRM only at 6-month). PPI consumption and symptoms were then assessed yearly. Data up to 3years are reported in this study (PP- and ITT-analysis). TIF was successfully performed in 45/46 patients; in one patient esophageal intubation was impossible. Perforation occurred in two cases. One patient required surgery within 6 months. Clinical follow-up was available for 42 patients at 6 months and 1 year, 35 patients at 2 years, and 31 patients at 3 years. At 1, 2, and 3 years, PPI consumption was stopped, respectively, in 64.3%, 62.9%, and 74.2% of cases (ITT-analysis: 58.7%, 56.4%, and 65.7%). GERD-HRQL and RSI scores decreased at least 50%, respectively, in 71.5% and 76.2%, 71.4% and 68.6%, and 67.7% of cases (ITT-analysis: 65.2% and 69.6%, 64.1% and 61.5%, and 60%). A significant improvement of both scores was observed up to 3 years. 6-month and 1-year functional follow-up were possible in 31 and 20 patients. HRM showed significant increase of the median lower esophageal sphincter length and rate of peristaltic waves. Esophageal pH-impedance recording found significantly fewer acid, proximal and total refluxes, and percentage of esophageal pH < 4 total time at 6 months, but not at 1 year. TIF by MUSE significantly improved symptoms and PPIs consumption up to 3 years. However, esophagitis still persisted in one-third of cases at 1 year and functional improvement at 6 months was not confirmed at 1 year. Severe complications requiring surgery occurred in two cases. GOV: ID: NCT03669874.

Long Term Risks of Proton Pump Inhibitor Administration: A Literature Review

Proton pump inhibitor (PPI) has become drug of choice for acid related disease. However, PPI tend to be overprescribed and becoming one of the highest burden for health cost. Some studies showed that PPI are prescribed unnecessarily. Recent evidences showed raised concerns over long term effects of PPI consumption. Several long term side effects such as increased incidence of gastric polyps, micronutrient absorption disorders, infections, and osteoporosis have been yearly discussed. In recent years there has been increased attention to new side effects such as dementia, chronic renal failure, and cardiovascular disorders. Therefore, some health associations had issued warning and guidance regarding long term PPI prescription.

Stretta therapy in the management of gastroesophageal reflux disease (GERD)

Treatment of gastroesophageal reflux disease (GERD) includes medical, surgical, and endoscopic intervention. The growing concerns of patients and physicians alike about adverse effects of chronic proton pump inhibitor (PPI) therapy or anti-reflux surgery have positioned endoscopic therapy for GERD on par with other therapeutic interventions. Endoscopic radiofrequency (RF) ablation (Stretta) has been used for more than 15 years and it is the most studied and followed endoscopic procedure for GERD. The technique itself has improved over the years and has been shown to be effective, safe and durable. Several meta-analyses and cohort studies have cemented the efficacy of the technique in improving patients’ health related quality of life, GERD symptoms, PPI consumption and esophageal acid exposure over more than 10 years follow up. Presently, endoscopic RF has been integrated into treatment guidelines of patients with GERD with diverse clinical scenarios.

Improved control of hypertension following laparoscopic fundoplication for gastroesophageal reflux disease.

This study aims to determine whether successful laparoscopic fundoplication for gastroesophageal reflux disease (GERD) can improve the control of hypertension. We conducted an observational study of GERD patients with hypertension. The esophageal and gastroesophageal symptoms of these patients were successfully treated with laparoscopic fundoplication, as measured by the reduced GERD symptoms and proton pump inhibitor consumption. A hypertension control scale was used to classify the use of antihypertensive medications and the quality of blood pressure control before and after anti-reflux surgery.Wilcoxon signed-ranks test was used for the statistical analyses. Seventy GERD patients were included in the analysis and followed up for a mean period of 3.5 ± 1.4 years. Prior to surgery, all participating patients were taking at least one class of antihypertensive medication, and 56 patients (80%) had intermittently high blood pressure. After surgery, the mean number of antihypertensive medication classes per patient was significantly reduced from 1.61 ± 0.77 pre-procedure to 1.27 ± 0.88 post-procedure (P < 0.001). The blood pressure of 48 of the 56 cases (86%) with preoperative intermittent high blood pressure returned to normal post procedure. A total of 50 patients (71%) recorded improvements on the hypertension control scale, with the overall mean score decreasing from 3.1 ± 1.0 preprocedure to 1.4 ± 1.0 post-procedure (P < 0.001). Therefore, successful laparoscopic fundoplication may result in better blood pressure control in some hypertensive GERD patients. This result suggests a possible connection between gastroesophageal reflux and hypertension.

The Effect of Helicobacter pylori Infection, Aging, and Consumption of Proton Pump Inhibitor on Fungal Colonization in the Stomach of Dyspeptic Patients.

Background: The importance of coinfection of Helicobacter pylori (H.pylori) and Candida albicans (C. albicans) in the development of gastric diseases is not known. In this study, the frequency of concurrent infection of H. pylori and C. albicans in dyspeptic patients was assessed while considering age, gender, and PPI consumption of patients.Methods: Gastric biopsies were taken from 74 yeast-positive dyspeptic patients and gastric disease, age, gender, and proton pump inhibitor (PPI) consumption of subjects were recorded. One antral biopsy was used for rapid urease test (RUT) and one for H. pylori and yeast cultivation and smear preparation. Bacterial isolates were identified according to spiral morphology and the biochemical characteristics. Yeast isolates were identified on Chromagar and by the Nested-PCR amplification of C. albicans-specific topoisomerase II gene. Twenty-seven biopsy smears were Gram-stained and examined by the light microscope for observing H. pylori and yeast cells.Results: Fifty-four (73%) of patients were >40 year. Of 68 patients with PPI consumption record, 46 (67.6%) consumed PPI (p = 0). Comparison of patients in peptic ulcer group (12, 16.2%) with (6, 8.1%) or without (6, 8.1%) H. pylori or in gastritis group (62, 83.8%) with (25, 33.8%) or without (37, 50%) H. pylori showed no significant difference (p > 0.05). Of the 46 patients who consumed PPI, 13 (17.5%) were H. pylori-positive and 33 (44.6%) H. pylori-negative (p = 0). Ten out of twenty-seven smears showed the occurrence of H. pylori cells, including three with yeast cells. Of the 17 H. pylori-negative smears, three showed the occurrence of yeast cells only. Yeasts stained Gram-positive or Gram-negative and appeared as single or budding cells.Conclusion: The older age and PPI consumption could favor fungal colonization in the human stomach. The occurrence of a considerable number of H. pylori-positive or H. pylori-negative patients with gastritis or peptic ulcer shows that co-infection of Candida and H. pylori or infection of yeast alone could be associated with dyspeptic diseases. The occurrence of yeast cells in gastric biopsies with different Gram's reactions indicates that fungi might change their cell wall components for establishing a persistent colonization in the stomach.

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.

Negative Effect of Proton-pump Inhibitors (PPIs) on Helicobacter pylori Growth, Morphology, and Urease Test and Recovery after PPI Removal--An In vitro Study.

Proton-pump inhibitor (PPI) consumption does lead to false-negative results of Helicobacter pylori diagnostic tests such as biopsy culture and rapid urease test (RUT). Helicobacter pylori isolates from 112 dyspeptic patients with (56.5%) or without (43.5%) PPI consumption were recruited for examining the negative effects of omeprazole (OMP), lansoprazole (LPZ), and pantoprazole (PAN) on H. pylori viability, morphology, and urease, in vitro. The effect of a sublethal concentration of OMP on bacterial features and their recovery after removal of OMP was also assessed. Of 112 culture-positive gastric biopsies, 87.5% were RUT positive and 12.5% RUT negative. There was a significant correlation between negative RUT results and PPI consumption (p < .05). OMP (minimum inhibitory concentration, MIC 32 μg/mL) and LPZ (MIC 8 μg/mL) inhibited the growth of 78.6% of H. pylori isolates. OMP and LPZ inhibited urease of 90.3% of isolates between 0 and 40 minutes and 54.4% between 20 and 40 minutes, respectively. PAN did not inhibit H. pylori growth and urease. Three 3-day (9 days) consecutive subcultures of H. pylori on brucella blood agar (BBA) supplemented with OMP resulted in reduced bacterial viability (1+), compared with control (4+), change of spiral morphology to coccoid, and reduction in pink color intensity in urea agar. Bacterial growth (1+), morphology, and urease test did not improve after the first 3-day and second 3-day (6 days) subcultures on BBA. However, relative recovery occurred after the third 3-day (9 days) subculture and complete recovery was observed after the fourth 3-day (12 days) subculture, as confluent growth (4+), 100% spiral cells, and strong urease test. Proton-pump Inhibitors exert transient negative effects on H. pylori viability, morphology, and urease test. Accordingly, cessation of PPI consumption at least 12 days before endoscopy could help avoiding false-negative results of H. pylori diagnostic tests.

Proton pump inhibitor therapy does not increase the incidence of spontaneous bacterial peritonitis in cirrhosis: A multicenter prospective study

Retrospective studies show an association between proton pump inhibitor (PPI) therapy and spontaneous bacterial peritonitis (SBP). We investigate the relationship between PPI and SBP in decompensated cirrhotic patients in a large nationwide prospective study. Seven hundred seventy patients with a diagnosis of decompensated cirrhosis were admitted consecutively in 23 hospitals in Argentina from March 2011 to April 2012; the patients were carefully investigated for PPI consumption in the previous 3 months. In total, 251 patients were excluded because of active gastrointestinal hemorrhage, antibiotic use during the preceding weeks, HIV-positive status and immunosuppressive therapy. Two hundred twenty-six out of 519 patients (43.5%) had received PPI therapy within the last 3 months. In 135 patients, PPIs were administered for longer than 2 weeks. A bacterial infection was shown in 255 patients (49.1%). SBP was diagnosed in 95 patients out of 394 patients with ascites (24.7%). There was no significant difference in the rate of PPI consumption between the infected and the non-infected patients (44.3% vs. 42.8%) or between the SBP patients and the patients with ascites without SBP (46% vs. 42%). In the SBP patients, the duration of PPI administration did not influence the rate of SBP occurrence. The type of bacteria and the origin of SBP infection were similar in the patients with and without PPI. In the current large, multicenter, prospective study, PPI therapy, specifically evaluated at admission of consecutive cirrhotic patients, was not associated with a higher risk of SBP.

Refractory GERD: What is it?

Refractory gastroesophageal reflux disease (GERD) is very common and may affect up to 40% of patients who use a proton pump inhibitor (PPI) once daily. Refractory GERD can present as incomplete or lack of response to PPI therapy. The disorder is clearly driven by patients, who present with a wide range of symptom severity and frequency while on PPI treatment. Poor compliance and improper timing of PPI consumption should always be excluded before further evaluation of this patient population. The putative mechanisms for refractory GERD include weakly acidic reflux, duodenogastroesophageal/bile reflux, visceral hypersensitivity, delayed gastric emptying, psychological comorbidity, and concomitant functional bowel disorders. Reduced PPI bioavailability, rapid PPI metabolism, PPI resistance, nocturnal reflux, and Helicobacter pylori infection status have very limited roles in refractory GERD. The contribution of eosinophilic esophagitis to refractory GERD is still unknown. Pill-induced esophagitis, Zollinger-Ellison syndrome, achalasia, and other disorders are rarely responsible for PPI failure and usually are not confused with GERD.

Relief of Reflux Symptoms after Endoscopic Gastroplication May Be Associated with Reduced Esophageal Acid Sensitivity: A Pilot Study

Although the new endoscopic techniques for the treatment of gastroesophageal reflux disease (GERD) lead to marked clinical benefit, the underlying mechanism of this is unknown. In this prospective study, the effect of endoscopic gastroplication was investigated in six patients with GERD, who were assessed before and 4 weeks after treatment. The effect on reflux symptoms, quality of life, proton pump inhibitor (PPI) consumption, reflux esophagitis, acid exposure, esophageal motility, lower esophageal sphincter pressure (LESP), and gastric emptying was measured. Esophageal acid sensitivity before and after treatment was investigated using a standardized acid provocation test, and compared with that of six age- and sex-matched healthy controls. Significant clinical benefit and discontinuation of PPI consumption after gastroplication was seen. Among the objectively measured parameters, only acid exposure was significantly reduced and gastric emptying significantly delayed. However, acid exposure remained pathologically high. Esophageal acid sensitivity was significantly reduced. The induction of heartburn and/or pain was abolished in four patients after gastroplication. In two patients the intensity of heartburn/pain was significantly reduced by 40 % or 60 %, and the time to provoke heartburn/pain significantly prolonged by 40% or 100%. These preliminary data suggest that the decrease of esophageal sensitivity to acid after endoscopic gastroplication is part of the mechanism responsible for the reduction of reflux symptoms.