Proton Pump Inhibitors Intake Research Articles

Three cases of symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) induced by proton-pump inhibitors.

Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE), previously termed drug-related baboon syndrome, is an uncommon drug eruption. It is characterized by symmetrical erythema involving the gluteal and/or inguinal area in association with one other intertriginous area in the absence of systemic involvement. It typically develops a few hours to days after drug exposure. The diagnosis is based on clinical presentation and drug history. The treatment consists mainly of withdrawal of the causative agent; corticosteroids (topical or systemic) are prescribed to accelerate the resolution. We present three cases that appeared after proton-pump inhibitors (PPIs) intake.

The effect of the use of proton pump inhibitors, serotonin uptake inhibitors, antihypertensive, and anti-inflammatory drugs on clinical outcomes of functional dental implants: Aretrospective study.

ObjectiveThe present retrospective study investigated the effect of chronic intake of proton pump inhibitors, selective serotonin uptake inhibitors, anti‐inflammatory, and antihypertensive drugs on the survival of dental implants and on the occurrence of peri‐implantitis.Materials and methodsSurvival analyses for implant failure and peri‐implantitis were performed patient level for each drug subcategory and for risk factors. The HR for each drug was calculated with adjusted models as compared with a control group made of subjects not assuming the specific drug. Multilevel logistic regression was used to explore the influence of implant‐level and patient‐level variables on the outcomes.ResultsA total of 270 subjects receiving 1118 dental implants were included, with a mean follow‐up time of 5.19 ± 4.22 years. After 10 years, the survival rate was 86.9% (patient level), and according to survival analysis, 61.3% of subjects were free from peri‐implantitis. The use of anti‐inflammatory medicines produced a significant effect (p = .04) on peri‐implantitis as compared to subjects not using the drug, with a 2.7‐year drop in the mean survival time. The HR was slightly above the level of significance in a semiadjusted model (p = .058). The multilevel analysis found a significant effect on the entire sample and not when considering only subjects with implants with more than 1‐year follow‐up.ConclusionsWe found a possible relationship between anti‐inflammatory drug use and the occurrence of peri‐implantitis in the examined cohort of patients, and no correlation for the other drugs.

Incidence, Pathogenesis, and Management of Proton Pump Inhibitor-Induced Nephrotoxicity.

Proton pump inhibitors are widely used in the treatment of various acid-related diseases and are among the most commonly used drugs. Studies estimate that 25-70% of proton pump inhibitors are prescribed for inappropriate treatments, doses, and indications, where the benefits of proton pump inhibitor use may be less than the risk of adverse drug reactions for many patients. Acute interstitial nephritis is an immune-mediated atypical kidney injury in the long-term use of proton pump inhibitors that causes problems for clinicians and patients. In this review, we summarize the current knowledge of proton pump inhibitors inducing acute interstitial nephritis, chronic kidney disease, and even end-stage renal disease in terms of incidence, pathogenesis, factors, clinical features, and diagnosis. We discuss how these factors change under conditions of acute interstitial nephritis, chronic kidney disease, and end-stage renal disease. The purpose of this review is to assess the current evidence to help clinicians and patients interpret the potential causal relationship between proton pump inhibitor intake and nephrotoxicity. This prompts clinicians to consider the appropriate dose and duration of proton pump inhibitor therapy to avoid inappropriate use.

Effects of Proton Pump Inhibitors Intake During Chemoradiotherapy for Rectal Cancer: a Retrospective Cohort Study.

Proton pump inhibitors (PPIs) are one of the most widely used drugs worldwide and are involved in several drug interactions. Recently, several studies have suggested that PPIs may interfere with the efficacy of capecitabine. This study primarily aimed to investigate the effects of PPI intake on the pathologic response rate of patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy with capecitabine. A retrospective study was conducted at a French Comprehensive Cancer Center. Patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy followed by surgery were included in the study. Demographic parameters, treatment characteristics, survival data, and PPI intake data were collected. Frequencies and percentages were reported for categorical variables and medians and interquartile ranges for continuous variables. Distribution of variables was compared according to PPI treatment using the chi-square test or Fisher's exact test for categorical data and nonparametric Wilcoxon tests for continuous variables. Survival data were estimated using the Kaplan-Meier method and compared using the log-rank test. In total, 215 patients were included, of whom 135 (62.8%) were men. The PPI intake frequency was 16.1%. The rate of complete pathological response was not significantly lower in patients on PPIs than in those not on PPIs (8.7% vs. 19%, p = 0.36). PPI intake was not associated with a statistically significant decrease in recurrence-free survival (hazard ratio [HR] = 1.26, 95% confidence interval [CI] 0.61-2.60, p = 0.54) or overall survival (HR = 0.95, 95% CI 0.33-2.76, p = 0.93). No significant association was observed between PPI co-medication and complete pathological response or survival in patients treated for locally advanced rectal cancer. However, the safety of PPIs could not be confirmed. Further ancillary studies of prospective clinical trials or studies using the Health Data Hub are necessary to explore the effects of PPIs on rectal cancer more accurately.

Severe Dysphagia is Rare After Magnetic Sphincter Augmentation

BackgroundDysphagia remains the most significant concern after anti-reflux surgery, including magnetic sphincter augmentation (MSA). The aim of this study was to evaluate postoperative dysphagia rates, its risk factors, and management after MSA.MethodsFrom a prospectively collected database of all 357 patients that underwent MSA at our institution, a total of 268 patients were included in our retrospective study. Postoperative dysphagia score, gastrointestinal symptoms, proton pump inhibitor intake, GERD-HRQL, Alimentary Satisfaction, and serial contrast swallow imaging were evaluated within standardized follow-up appointments. To determine patients’ characteristics and surgical factors associated with postoperative dysphagia, a multivariable logistic regression analysis was performed.ResultsAt a median follow-up of 23 months, none of the patients presented with severe dysphagia, defined as the inability to swallow solids or/and liquids. 1% of the patients underwent endoscopic dilatation, and 1% had been treated conservatively for dysphagia. 2% of the patients needed re-operation, most commonly due to recurrent hiatal hernia. Two patients underwent device removal due to unspecific discomfort and pain. No migration of the device or erosion by the device was seen. The LINX® device size ≤ 13 was found to be the only factor associated with postoperative dysphagia (OR 5.90 (95% CI 1.4–24.8)). The postoperative total GERD-HRQL score was significantly lower than preoperative total score (2 vs. 19; p = 0.001), and daily heartburn, regurgitations, and respiratory complains improved in 228/241 (95%), 131/138 (95%) and 92/97 (95%) of patients, respectively.ConclusionsDysphagia requiring endoscopic or surgical intervention was rare after MSA in a large case series. LINX® devices with a size < 13 were shown to be an independent risk factor for developing postoperative dysphagia.

Systematic Retesting for Helicobacter pylori: The Potential Overestimation of Suppressive Conditions.

Background and Aims In contrast to guideline recommendations, endoscopic testing for Helicobacter pylori is frequently performed under Helicobacter pylori suppressive conditions, e.g., intake of proton-pump inhibitors (PPI), preceded antibiotic treatment, or recent gastrointestinal bleeding. Our study's aim was to retest patients with—under suppressive conditions—negative test results. This was carried out in order to examine the rate of false negative tests previously gathered under suppressive conditions. Methods The trial was conducted in a large patient collective in a university hospital. Every elective esophagogastroduodenoscopy from in- and outpatients was included. Prior to endoscopy, suppressive conditions were collected via standardized questionnaire. If Helicobacter pylori testing was indicated, both helicobacter urease test and histology were performed in analogy to the Sydney classification. In case of a negative result under suppressive conditions, the patient was reinvited after, if possible, withdrawal of suppressive condition in order to perform a urea breath test (UBT). Results 1,216 patients were included (median 59 years, 72.0% inpatients, 28.0% outpatients). Overall, 60.6% (737) were under Helicobacter pylori suppressive conditions. The main suppressive condition was intake of PPIs (54.5%). In 53.7% (653) of all included cases, Helicobacter pylori testing was performed. Of those, 14.1% (92) had a positive test, and 85.9% (561) were negative. Out of the patients with negative result, 50.8% (285) were tested under suppressive conditions and consequently invited for retesting via UBT. In 20.4% (45), suppressive conditions could not be ceased. In 22.8% (65), retesting was conducted. Of those, 98.5% (64) congruently presented a negative result again, and only 1.5% (1) was positive for Helicobacter pylori. Conclusion Many patients undergoing esophagogastroduodenoscopy in everyday clinical practice are tested for Helicobacter pylori under suppressive conditions leading to a potentially higher risk of false negative results. However, our research shows that this issue might be overestimated.

Awareness of drug laboratory test interactions is important for prevention of unnecessary additional diagnostics: An example

BackgroundElevated levels of Chromogranin A (CgA) may be indicative of a neuroendocrine tumour (NET), but increased levels are also observed after intake of proton pump inhibitors (PPIs). The incidence of diagnostic confusion because of this drug-laboratory test interaction (DLTI) was examined. MethodsMedical records of 238 patients with elevated CgA concentrations were obtained from three hospitals. The following data were extracted: PPI prescription at the time of CgA measurement, medical decision making based on elevated CgA concentrations, final diagnosis, comorbidity and other prescribed drugs. ResultsFrom 238 patients with elevated CgA concentrations, 132 used PPIs. Of these patients, 57 patients did not have a NET. In 9 of these 57 patients (16%), diagnostic work up revealed no medical cause of an elevated CgA concentration. Somatostatin receptor imaging was ordered in 4 out of 9 cases, with no abnormalities observed. In 6 out of 9 cases, CgA measurement was repeated after PPI discontinuation resulting in normalisation of CgA concentrations. ConclusionIn this retrospective patient record study we observed that part of the elevated CgA concentrations in patients could be caused by the usage of PPIs causing unnecessary diagnostic work-up for the exclusion of a NET. These observations illustrate the need for better DLTI awareness.

Gastric Corpus Hypertrophy with a Bleeding Hyperplastic Polyp in a Helicobacter pylori-naive Subject after Long-term Proton Pump Inhibitor Use

A 22-year-old man presented with recurrent dizziness and melena. He had no remarkable medical history except for the reflux symptoms for which 18 months of proton pump inhibitor (PPI) intake was required. Gastroscopy revealed a 1-cm, blood-tinged polyp within the gastric rugae. A thickened gastric corpus was observed with a regular arrangement of collecting venules on its surface. Hyperplastic foveolar epithelium was observed in the biopsied specimens from the fundus and gastric rugae. The diagnosis after polypectomy was gastric hyperplastic polyp. Abdominal CT revealed hypertrophy only in the gastric corpus without antral involvement. Increased levels of serum pepsinogen I (&gt;160 ng/mL), pepsinogen II (&gt;50 ng/mL), chromogranin A (&gt;1,800 ng/mL), and gastrin (534 pg/mL) were noted. Three months after PPI discontinuation, CT revealed improvement of the hypertrophic gastric corpus. Serum chromogranin A and gastrin levels decreased to 950.4 ng/mL and 517.0 pg/mL, respectively. Herein, we report a young, Helicobacter pylori-naive patient with prominent hyperplasia in the gastric corpus and a bleeding hyperplastic polyp after long-term PPI use.

Evaluation of Antireflux Mucosectomy for Severe Gastroesophageal Reflux Disease: Medium-Term Results of a Pilot Study.

Background Antireflux mucosectomy, a new endoscopic treatment for gastroesophageal reflux disease, consists of endoscopic mucosal resection at the esophagogastric junction. This study aim was to evaluate the medium-term efficacy of the antireflux mucosectomy technique for patients with severe gastroesophageal reflux disease symptoms (proton pump inhibitor treatment-dependent or proton pump inhibitor treatment-resistant gastroesophageal reflux disease). Methods Between January 2017 and June 2018, 13 patients with severe gastroesophageal reflux disease without hiatal hernia, with positive pH reflux, were included in this monocentric prospective pilot study. The primary outcome was clinical success, defined by improvement evaluated by the Gastroesophageal Reflux Disease Health Related Quality of Life Questionnaire at 24 months. Secondary outcomes were technical success, decreased use of proton pump inhibitors, patient satisfaction, and adverse events. Results Thirteen patients [females = 8 (62%)], mean age 59 (range, 54-68), were included. The antireflux mucosectomy procedure had technical success in all patients. At 24 months, for 11 patients, gastroesophageal reflux disease symptoms were significantly improved, and mean gastroesophageal reflux disease score decreased from 33 (range, 26-42) to 3 (range, 0-7) (p = 0.001). Ninety-one percent (n = 10) of patients had a lower proton pump inhibitor intake at 24 months. One patient had 3 endoscopic balloon dilatations for EGJ stenosis, two patients had melena ten days after procedure, and seven patients had thoracic or abdominal pain. Patient's satisfaction at 24 months was 81%. Conclusions In patients with severe gastroesophageal reflux disease, despite occurrence of several short-term adverse events, antireflux mucosectomy seemed effective in improving gastroesophageal reflux disease symptoms at 24 months. This trial is registered with ClinicalTrials: NCT03357809.

Glucocorticoids Are Not Associated with Bone Mineral Density in Patients with Polymyalgia Rheumatica, Giant Cell Arteritis and Other Vasculitides-Cross-Sectional Baseline Analysis of the Prospective Rh-GIOP Cohort.

Background: Glucocorticoids (GCs) can cause osteoporosis (OP). Prior observational research on bone density and the effects of GCs in polymyalgia rheumatica (PMR) and vasculitides is scarce and inconclusive. Methods: Rh-GIOP is a prospective cohort study of bone health in patients with inflammatory rheumatic diseases. In this cross-sectional baseline analysis, we focused on patients with PMR and different forms of vasculitides. Multivariable linear regression was used to model the effect of current and cumulative GC intake on the minimum T-score at any site (mTs; at either lumbar spine or hip), with comprehensive adjustment for confounders. In separate models, GCs were modelled both as continuous and categorical predictors. Sensitivity analyses, stratifying by measurement site and disease, were conducted. Results: A total of 198 patients, with a mean age of 67.7 ± 11.4 years and a mean disease duration of 5.3 ± 6.3 years, were included. Most patients suffered from PMR (36%), giant cell arteritis (26%) or granulomatosis with polyangiitis (17%). Women comprised 66.7% of the patients, and 87.4% were currently taking GCs. The mean CRP was 13.2 ± 26.1 mg/L. OP diagnosed by dual energy X-ray absorptiometry (DXA) (T-score ≤ −2.5) was present in 19.7% of the patients. While 88% were taking vitamin D supplements, calcium supplementation (4%) and treatment with anti-resorptive agents (17%) were relatively infrequent. Only 7% had a vitamin D deficit. Neither current (β(continuous model) = −0.01, 97.5% CI –0.02 to 0.01; p(all models) ≥ 0.49) nor cumulative (β(continuous model) = 0.01, 97.5% CI −0.04 to 0.07; p(all models) ≥ 0.35) GC doses were associated with mTs in any model. CRP was not associated with mTs in any model (p(all models) ≥ 0.56), and no interaction between CRP and GC intake was observed (p for interaction(all models) ≥ 0.32). Across all analyses, lower body mass index (p(all models) ≤ 0.01), history of vertebral fractures (p(all models) ≤ 0.02) and proton-pump inhibitor intake (p(all models) ≤ 0.04) were associated with bone loss. Sensitivity analyses with femoral neck and lumbar spine T-scores as dependent variables led to similar results as the analysis that excluded patients with PMR. Conclusions: In this cohort of PMR and vasculitides, we found a similar prevalence of OP by DXA to the overall elderly German population. Vitamin D supplementation was very common, and vitamin D insufficiency was less frequent than expected in Germans. There was no association between current or cumulative GC intake, CRP and impaired bone density. Proton-pump inhibitors seem to be a major, but somewhat neglected, risk factor for OP and should be given more attention. Our findings require confirmation from longitudinal analyses of the Rh-GIOP and other cohorts.

Duodenal Dysbiosis and Relation to the Efficacy of Proton Pump Inhibitors in Functional Dyspepsia.

Proton pump inhibitors (PPI) may improve symptoms in functional dyspepsia (FD) through duodenal eosinophil-reducing effects. However, the contribution of the microbiome to FD symptoms and its interaction with PPI remains elusive. Aseptic duodenal brushings and biopsies were performed before and after PPI intake (4 weeks Pantoprazole 40 mg daily, FD-starters and controls) or withdrawal (2 months, FD-stoppers) for 16S-rRNA sequencing. Between- and within-group changes in genera or diversity and associations with symptoms or duodenal factors were analyzed. In total, 30 controls, 28 FD-starters and 19 FD-stoppers were followed. Mucus-associated Porphyromonas was lower in FD-starters vs. controls and correlated with symptoms in FD and duodenal eosinophils in both groups, while Streptococcus correlated with eosinophils in controls. Although clinical and eosinophil-reducing effects of PPI therapy were unrelated to microbiota changes in FD-starters, increased Streptococcus was associated with duodenal PPI effects in controls and remained higher despite withdrawal of long-term PPI therapy in FD-stoppers. Thus, duodenal microbiome analysis demonstrated differential mucus-associated genera, with a potential role of Porphyromonas in FD pathophysiology. While beneficial effects of short-term PPI therapy were not associated with microbial changes in FD-starters, increased Streptococcus and its association with PPIeffects in controls suggest a role for duodenal dysbiosis after long-term PPI therapy.

Is Gut Involvement a Cause or Effect of COVID-19?

Digestive disorder symptoms in COVID-19 may be similar in form to post-infectious functional gastrointestinal disorder (PI-FGID). To cause clinical effects, SARS-CoV-2 must reach the bowels and gastric hypochlorhydria may facilitate such transit. Asian elderly are predisposed to greater infection rate and severity of COVID-19, and the high prevalence of gastric atrophy and intake of proton-pump inhibitor in this aged group might explain the risk. Persistence shedding of SARS-CoV-2 in stools indicates that faecal transmission should not be disregarded. Gut involvement in COVID-19 is mediated by angiotensin-converting enzyme 2 (ACE2) receptor, which serves as the entry point for SARS-CoV-2 in the small bowel. ACE2 dysregulation has an impact on the homeostasis of gut microbiota and altered inflammatory response. Liver injury is variable in COVID-19 and is likely a result of by-stander effects rather than actual viropathic process. Further research is needed to understand if gut involvement is a cause or effect of SARS-CoV-2.

SP5.1.8 Long term outcomes of laparoscopic magnetic sphincter augmentation for gastro-oesophageal reflux disease: High patient satisfaction with low dysphagia rates

Abstract Aims Laparoscopic magnetic sphincter augmentation (MSA) or LINX® procedure is gaining popularity as a treatment for gastro-oesophageal reflux disease. We looked at the long-term outcomes of this procedure with regards to its efficacy, in particular studying the dysphagia rate in relation to the LINX® device size. Methods Postal questionnaires were sent to all patients who underwent MSA procedure between 2012-2019 at a single institution. Patients were asked to quantify, as a percentage, their symptom resolution, proton pump inhibitor (PPI) intake and side effects. Results 124 patients (male:female ratio was 45:55) underwent MSA procedure, with 82 responding to the questionnaire. Patients' age range was 18-71 years (median 49). Over 90% of patients reported improvements in reflux symptoms with 75% reporting complete resolution. 67% of patients no longer required PPI medication, whilst 21% of patients had &amp;gt;50% reduction in their medication. Post-operative dysphagia occurred in 59% of patients at 3 months, which decreased to 16% at 1 year. There was no significant difference in size of LINX® device used between patients with dysphagia at ≥ 1 year versus those without dysphagia at ≥ 1 year (p = 0.554). In total 3 patients (2%) required explantation of the LINX® device. Overall 86% of patients rated their outcomes as satisfactory or very satisfactory. Conclusions Our 7 years of experience with laparoscopic MSA has demonstrated that this procedure is safe with high patient satisfaction rates. Dysphagia, although common in the early post-operative period, usually resolves within 3-6 months and is unrelated to LINX® device size.

Risk of SARS-Cov-2 Infection Among Proton Pump Inhibitors Users:

Public health is affected seriously by COVID-19. Its mortality rate varies within different nations and identification of its risk factors is in progress. Here, we systematically reviewed articles that have evaluated the association between proton pump inhibitors (PPIs) intake and SARS-CoV-2 infection. PubMed, Google Scholar, Scopus, and Cochrane databases from their inception till 2nd December 2020 were systematically searched to obtain any possible article for inclusion. Results of this research reveal that After screening and removing unrelated or duplicate articles by the title and abstract by two independent reviewers, 6 articles were included. Results revealed a direct and dose-dependent relationship among PPIs intake and possibility of infection with SARS-CoV-2, the severity of the clinical manifestations of the COVID-19, and expression of SARS-CoV-2 receptors in the kidney and liver tissues. In Conclusion, PPIs increase the risk of the infection with SARS-CoV-2 and cause severe clinical outcomes in the COVID-19 patient. They should be used when a clear indication is present at the lowest effective dose.

Expanded Indication for Magnetic Sphincter Augmentation: Outcomes in Weakly Acidic Reflux Compared to Standard GERD Patients

BackgroundMagnetic sphincter augmentation (MSA) is a modern surgical anti-reflux technique with proven efficacy and low postoperative morbidity in patients with acidic reflux. The aim of this retrospective review study was to evaluate the symptomatic outcome of MSA in patients with weakly acidic reflux. MethodsFrom a prospectively collected clinical database, comprising all 327 patients that underwent MSA at our institution, a total of 67 patients with preoperative weakly acidic reflux measured in the 24-h impedance-pH-metry were identified. Postoperative gastrointestinal symptoms, proton pump inhibitor intake (PPI), GERD Health-Related Quality-of-Life (GERD-HRQL), alimentary satisfaction (AS), and patients’ overall satisfaction were evaluated within highly standardized follow-up appointments. Furthermore, outcome of these patients was compared to the postoperative outcome of a comparable group of patients with a preoperative acidic reflux. ResultsAt a median follow-up of 24 months, none of the patients with weakly acidic reflux presented with persistent dysphagia, or underwent endoscopic dilatation or reoperation. The postoperative GERD-HRQL score was significantly reduced (2 vs. 20; p = 0.001) and the median AS was 9/10. Preoperative daily heartburn, regurgitations, and respiratory complaints were improved in 95%, 95%, and 96% of patients, respectively. A total of 10% of the patients continued to use PPIs postoperatively. No significant difference was observed in terms of postoperative outcome or quality of life when comparing weakly acidic reflux patients with those diagnosed with preoperative acidic reflux. ConclusionMagnetic sphincter augmentation significantly improves GERD-related symptoms and quality of life in patients with weakly acidic reflux with very low postoperative morbidity.

Вибір оптимального інгібітору протонної помпи для пацієнтів з ішемічною хворобою серця, які потребують проведення подвійної антитромбоцитарної терапії

Висока захворюваність і смертність від серцево-судинних захворювань призвели до необхідності широкого використання антитромбоцитарних засобів у клінічній практиці. Найбільш перспективною вважається комбінована антиагрегантна терапія з використанням препаратів, що мають різні механізми впливу на тромбоцитарну ланку гемостазу, за рахунок чого можна досягти вираженого синергічного ефекту. У нашій країні переважно призначається комбінація ацетилсаліцилової кислоти і клопідогрелю, яку часто називають подвійною антитромбоцитарною терапією (ПАТ). Для зменшення ризиків розвитку шлунково-кишкових ускладнень при використанні ПАТ рекомендований прийом інгібіторів протонної помпи (ІПП), проте в деяких дослідженнях згадується, що одночасне призначення ІПП та клопідогрелю в перспективі підвищує ризик виникнення несприятливих серцево-судинних подій, до яких відносять інфаркт міо-карда, інсульт, нестабільну стенокардію, необхідність повторних коронарних втручань і коронарну смерть. У зв’язку з цим представляється актуальною проблема розробки підходів диференційованого застосування ІПП у пацієнтів, які отримують ПАТ. Надано огляд літератури з означеної вище проблематики, наведено результати досліджень із вивчення впливу різних ІПП на клінічні наслідки у хворих, які приймають клопі-догрель.

A PROTON PUMP INHIBITOR ALTERS THE pH OF THE HUMAN UTERINE CAVITY

To present two cases of increased pH of the uterine cavity after taking lansoprazole, an oral proton pump inhibitor (PPI). Case study. We examined infertile women to see whether chronic endometritis (CE) existed, through assessment of endometrial plasma cells (CD138 immunostained cells) and uterine microbiota by sequencing the 16S ribosomal RNA gene (Varinos Inc., Japan). CE was diagnosed applying the criteria (>5.15/10xmm2) reported by Liu et al. (1). We also examined the intrauterine pH directly on the endometrial surface using a Portal pH Meter (Japan Asch Inc., Japan) that has been utilized for the esophageal mucosa of esophagitis (2). We have reported in ESHRE annual meeting 2020 that intrauterine pH is weakly acidic (5.58±0.59) and it increases in the case of CE (6.67±0.39). Patient 1: A 44-year-old infertile woman noticed changes of her vaginal discharge after taking orally lansoprazole 30 mg for reflux esophagitis. Her initial intrauterine condition had been normal with pH: 6.3, Lactobacillus: 97%, and CD138-positive cells: 1.7/10xmm2. After PPI intake for a month, her intrauterine pH rose to 7.0, which suggested existence of CE. Therefore, we collected the endometrial tissue again and performed microbiota and pathological tests: Lactobacillus was 99% and CD138-positive cells were 1.6/10xmm2, which did not indicate CE histologically and bacterially. After discontinuing PPI, her intrauterine pH dropped to 6.7 with Lactobacillus: 97% and CD138-positive cells: 2.0/10xmm2. Patient 2: A 47-year-old woman, whose initial uterine pH had been 6.4, noticed a change of odor of vaginal discharge after taking PPI (lansoprazole 30 mg daily) for gastric ulcer. Her intrauterine pH rose to 7.1 with Lactobacillus :9.1% and CD138-positive cells: 0.7/10xmm2. After discontinuation of PPI, her intrauterine pH dropped to 6.2 with no CD138-positive cells, but Lactobacillus was 2.60%. We experienced two cases in which the pH of uterine cavity increased while taking oral PPI. We have reported that the uterine luminal pH in human is weakly acidic (around 6.0) and that the pH increases in the presence of CE or abnormal endometrial microbiota. In animals, such as mice (3) and mares (4), the uterine luminal pH is acidic at the time of implantation, and the acidic environment in the uterus is considered to be important for embryo implantation, and the vacuolar H + -ATPase pump, which is a type of proton pump, is expressed in the endometrium at the time of implantation in bovine (5) and mice (2), but there have been no reports in humans. These 2 cases which we presented here suggest that some proton pumps are also expressed in the endometrium and acidify the uterine cavity in humans, which could control the intrauterine environment independently of inflammation or microbiota.

Proton Pump Inhibitors and Gastric Cancer

Concerns have been raised regarding the long-term use of proton pump inhibitors (PPIs) as an important risk factor for gastric cancer in clinical practice. PPIs can cause hypergastrinemia at clinical doses, and hypergastrinemia has been reported to induce malignant neoplasms in the stomach in previous animal studies. In humans, the proliferation of enterochromaffin-like (ECL) cells induced by hypergastrinemia is suspected as a potential mechanism of gastric cancer. Meanwhile, persistent Helicobacter pylori (H. pylori) infection causes gastric atrophic change, which itself is a major cause of gastric cancer, and it can further increase the risk of gastric cancer by strengthening corpus atrophy through interaction with PPIs. Recent epidemiologic studies have reported an important link between long-term PPI intake and gastric cancer risk even after successful eradication of H. pylori. However, due to the methodological limitations of observational clinical studies, the causal relationship is still not clear, and a recent big data-based study reported that long-term PPI use was not related to gastric cancer incidence. Taken together, despite the potential detrimental effects of PPIs, it is currently difficult to draw a definite conclusion about its association with gastric cancer. To minimize the possibility of gastric cancer in H. pylori-infected patients or precancerous lesions in long-term PPI users, long-term PPI administration should be limited to the minimum effective dose, and antibacterial treatment for H. pylori should be considered.

Diagnosis of Helicobacter pylori Infection by the Arrangement of Collecting Venules Using White Light Endoscopy: Evaluation of Interobserver Agreement

Background: Regular arrangement of collecting venules (RAC) in gastric mucosa accurately identifies patients without Helicobacter pylori (H pylori) infection. The aim of our study was to evaluate the reproducibility of RAC using white light endoscopy without magnification, in a European country, and to assess the impact of proton pump inhibitors (PPIs). Methods: A multicenter prospective study with image capture of the distal lesser gastric curvature and gastric biopsies was performed. The presence of starfish-like minute points regularly distributed throughout lesser curvature was considered as RAC positive (RAC+). A set of 20 images was used for the training phase and inter and intra-observer agreements were calculated. Results: 174 patients were included and 85 (48.9%) were taking PPIs. Kappa values for interobserver and intra-observer agreements were substantial (0.786) and excellent (0.906), respectively. H. pylori infection was diagnosed in 29 patients (16.7%): 10/85 with PPIs and 19/89 without PPIs (11.8% vs. 21.3%; p = 0.09). All RAC + patients were free of H. pylori infection, with a sensitivity and negative predictive value of 100%, regardless of PPI intake. Conclusion: The endoscopic diagnosis of H. pylori by RAC is an easy-to-learn and highly reproducible technique, even with PPI intake. Our results warrant RAC as a real-time diagnostic method for H. pylori-negative infection in Western practice.

Additional fundophrenicopexia, after Nissen fundoplication, reduces postoperative dysphagia and re-operation rate in the long-term follow up

BackgroundVarious technical modifications of Nissen fundoplication (NF) that aim to improve patients’ outcomes have been discussed. This study aims to evaluate the effect of division of the short gastric vessels (SGV) and the addition of a standardized fundophrenicopexia on the postoperative outcome after NF.Methods283 consecutive patients with GERD treated with NF were divided into four groups following consecutive time periods: with division of the SGV and without fundophrenicopexia (group A), with division of the SGV and with fundophrenicopexia (group B), without division of the SGV and with fundophrenicopexia (group C) and without division of the SGV and without fundophrenicopexia (group D). Postoperative contrast swallow, dysphagia scoring, GEDR-HRQL and proton pump inhibitor intake were evaluated. A comparative analysis of patients with division of the SGV and those without (161 A + B vs. 122 C + D), and patients with fundophrenicopexia and those without (78 A vs. 83 B and 49 C vs. 73 D) was performed.ResultsFundophrenicopexia reduced postoperative dysphagia rates (0 group C vs. 5 group D, p = 0.021) in patients where the SGV were preserved and reoperation rates (1 group B vs. 7 group A, p = 0.017) in patients where the SGV were divided. There was no significant difference in the postoperative rates of heartburn relief, dysphagia, gas bloating syndrome, interventions, re-fundoplication and the GERD-HRQL score between groups A + B and C + D, respectively.ConclusionStandardized additional fundophrenicopexia in patients undergoing Nissen fundoplication significantly reduces postoperative dysphagia in patients without division of the SGV and reoperation rates in patients with division of the SGV. Division of the SGV has no influence on the postoperative outcome of NF.