Meta-analyses: Does long-term PPI use increase the risk of gastric premalignant lesions?

Background: Proton pump inhibitors (PPIs) are the most effective agents available for reducing acid secretion. They are used for medical treatment of various acid-related disorders. PPIs are used extensively and for extended periods of time in gastroesophageal reflux disease (GERD). A troublesome issue regarding maintenance therapy has been the propensity of PPI-treated patients to develop chronic atrophic gastritis while on therapy that could theoretically lead to an increased incidence of gastric cancer. In addition, animal studies have raised concern for development of enterochromaffin-like cell hyperplasia and carcinoid tumors in the stomachs of mice receiving high dose PPIs. Current literature does not provide a clear-cut conclusion on the subject and the reports are sometimes contradictory. Therefore, this study is a systematic review of the available literature to address the safety of long-term PPI use and its relation to the development of malignant/premalignant gastric lesions. Methods: A literature search of biomedical databases was performed. The reference lists of retrieved articles were reviewed to further identify relevant trials. We hand-searched the abstracts of the American Digestive Disease Week (DDW) and the United European Gastroenterology Week (UEGW) from 1995 to 2013. Only randomized clinical trials (RCTs) that used PPIs as the primary treatment for at least six month versus no treatment, placebo, antacid or anti-reflux surgery (ARS) were included. Two reviewers independently extracted the data. Discrepancies in the interpretation were resolved by consensus. All analyses of outcomes were based on the intention-to-treat principle. We performed statistical analysis using Review Manager software. The effect measure of choice was relative risk (RR) for dichotomous data. Results: Six RCTs with a total of 785 patients met the inclusion criteria. Two multicenter RCTs compared Esomeprazole with placebo. One RCT compared omeprazole with ARS. Two RCTs compared omeprazole with ranitidine and one RCT compared lansoprazole with ranitidine. Four of the included RCTs had moderate risk of bias and two had low risk of bias. The number of patients with increased corporal atrophy score, intestinal metaplasia score and chronic antral inflammation did not statistically differ between the PPI maintenance group and controls. Similar results were found when ECL-cell hyperplasia was assessed between the groups. ConclusionS: Maintenance PPIs did not have an association with increased gastric atrophic changes or ECL-cell hyperplasia for at least three years in RCTs

Impact of immunosuppressive treatment on liver fibrosis in autoimmune hepatitis

The impact of treatment on progression of fibrosis in autoimmune hepatitis (AIH) is unknown. We assessed the changes in liver fibrosis before and after treatment among these patients. Nineteen AIH patients who had paired liver biopsies were studied. Of these, seven had been treated with 6 months of cyclosporine A and the rest with 6 months of prednisolone for induction of remission. Thereafter all had been maintained on azathioprine. Biopsy specimens before and after treatment were reviewed by one pathologist and scored by the Ishak method. Mean fibrosis stages before and after treatment were compared. Also, factors predicting significant fibrosis (stage �3) and cirrhosis (stage �5) at presentation were assessed. Mean interval between biopsies was 3.38 years. Mean fibrosis stage decreased from 4.53 to 2.16 following treatment (P < 0.001). Mean decrement in inflammatory grade was 8 scores (range, 4-10) in patients in whom fibrosis improved, and 2 scores (range, 0-4) in patients in whom fibrosis did not decrease after treatment (P < 0.001). ALT-to-platelet ratio was the best predictor of significant fibrosis and also cirrhosis. Fibrosis commonly improves after immunosuppressive treatment in AIH. ALT-to-platelet ratio can predict accurately the presence of significant fibrosis and cirrhosis in AIH. © 2005 Springer Science+Business Media, Inc

Epidemiologic features of upper gastrointestinal tract cancers in Northeastern Iran

Previous studies have shown that oesophageal and gastric cancers are the most common causes of cancer death in the Golestan Province, Iran. In 2001, we established Atrak Clinic, a referral clinic for gastrointestinal (GI) diseases in Gonbad, the major city of eastern Golestan, which has permitted, for the first time in this region, endoscopic localisation and histologic examination of upper GI cancers. Among the initial 682 patients seen at Atrak Clinic, 370 were confirmed historically to have cancer, including 223 (60) oesophageal squamous cell cancers (ESCC), 22 (6) oesophageal adenocarcinomas (EAC), 58 (16) gastric cardia adenocarcinomas (GCA), and 58 (16) gastric noncardia adenocarcinomas. The proportional occurrence of these four main site-cell type subdivisions of upper GI cancers in Golestan is similar to that seen in Linxian, China, another area of high ESCC incidence, and is markedly different from the current proportions in many Western countries. Questioning of patients about exposure to some known and suspected risk factors for squamous cell oesophageal cancer confirmed a negligible history of consumption of alcohol, little use of cigarettes or nass (tobacco, lime and ash), and a low intake of opium, suggesting that the high rates of ESCC seen in northeastern Iran must have other important risk factors that remain speculative or unknown. Further studies are needed to define more precisely the patterns of upper GI cancer incidence, to test other previously suspected risk factors, and to find new significant risk factors in this high-risk area. © 2004 Cancer Research UK

Human Echinococcosis Mortality in the United States, 1990–2007

Human echinococcosis is a parasitic disease that affects an estimated 2–3 million people and results in an annual monetary loss of over $750,000,000 worldwide. It results in the development of life threatening tissue cysts, primarily in the liver and lung, following accidental ingestion of eggs in infected dog, fox or wild canine feces. Echinococcus parasites have a complex, two-host lifecycle (such as in dogs and sheep) in which humans are an aberrant, dead-end host. The vast majority of cases of human echinococcosis occur outside of the United States (US); however, cases within the US do occur. In this study, the authors examined death certificate data of US residents from 1990–2007 in which echinococcosis was listed as one of the diagnoses at death. The analysis demonstrated 41 echinococcosis-related deaths over the 18-year study period with foreign-born persons accounting for the majority of the deaths. This study helps quantify echinococcosis deaths among US residents and adds further support to the importance of funding echinococcosis prevention research

Prospective Acid Reflux Study of Iran (PARSI): Methodology and study design

<p>Abstract</p> <p>Background</p> <p>Gastroesophageal reflux disease is a common and chronic disorder but long term, prospective studies of the fate of patients seeking medical advice are scarce. This is especially prominent when looking at non-erosive reflux disease (NERD) patients.</p> <p>Methods</p> <p>We designed a prospective cohort to assess the long term outcome of GERD patients referring to gastroenterologists. Consecutive consenting patients, 15 years of age and older, presenting with symptoms suggestive of GERD referring to our outpatient clinics undergo a 30 minute interview. Upper gastrointestinal endoscopy is performed for them with protocol biopsies and blood samples are drawn. Patients are then treated according to a set protocol and followed regularly either in person or by telephone for at least 10 years.</p> <p>Discussion</p> <p>Our data show that such a study is feasible and follow-ups, which are the main concern, can be done in a fairly reliable way to collect data. The results of this study will help to clarify the course of various subgroups of GERD patients after coming to medical attention and their response to treatment considering different variables. In addition, the basic symptoms and biological database will fuel further molecular epidemiologic studies.</p

Diagnostic Accuracy of Age and Alarm Symptoms for Upper GI Malignancy in Patients with Dyspepsia in a GI Clinic: A 7-Year Cross-Sectional Study

<div><h3>Objectives</h3><p>We investigated whether using demographic characteristics and alarm symptoms can accurately predict cancer in patients with dyspepsia in Iran, where upper GI cancers and <em>H. pylori</em> infection are common.</p> <h3>Methods</h3><p>All consecutive patients referred to a tertiary gastroenterology clinic in Tehran, Iran, from 2002 to 2009 were invited to participate in this study. Each patient completed a standard questionnaire and underwent upper gastrointestinal endoscopy. Alarm symptoms included in the questionnaire were weight loss, dysphagia, GI bleeding, and persistent vomiting. We used logistic regression models to estimate the diagnostic value of each variable in combination with other ones, and to develop a risk-prediction model.</p> <h3>Results</h3><p>A total of 2,847 patients with dyspepsia participated in this study, of whom 87 (3.1%) had upper GI malignancy. Patients reporting at least one of the alarm symptoms constituted 66.7% of cancer patients compared to 38.9% in patients without cancer (p<0.001). Esophageal or gastric cancers in patients with dyspepsia was associated with older age, being male, and symptoms of weight loss and vomiting. Each single predictor had low sensitivity and specificity. Using a combination of age, alarm symptoms, and smoking, we built a risk-prediction model that distinguished between high-risk and low-risk individuals with an area under the ROC curve of 0.85 and acceptable calibration.</p> <h3>Conclusions</h3><p>None of the predictors demonstrated high diagnostic accuracy. While our risk-prediction model had reasonable accuracy, some cancer cases would have remained undiagnosed. Therefore, where available, low cost endoscopy may be preferable for dyspeptic older patient or those with history of weight loss.</p> </div

A population-based survey of the epidemiology of symptom-defined gastroesophageal reflux disease: the Systematic Investigation of Gastrointestinal Diseases in China

<p>Abstract</p> <p>Background</p> <p>The epidemiology of gastroesophageal reflux disease (GERD) has yet to be investigated using the symptomatic threshold criteria recommended by the Montreal Definition. This study aimed to determine the prevalence of symptom-defined GERD across five regions of China, and to investigate variables associated with GERD.</p> <p>Methods</p> <p>A representative sample of 18 000 adults (aged 18-80 years) were selected equally from rural and urban areas in each region (n = 1800). According to the Montreal Definition, GERD is present when mild symptoms of heartburn and/or regurgitation occur on ≥2 days a week, or moderate-to-severe symptoms of heartburn and/or regurgitation occur on ≥1 day a week.</p> <p>Results</p> <p>In total, 16 091 participants completed the survey (response rate: 89.4%) and 16 078 responses were suitable for analysis. Applying the Montreal criteria, the prevalence of symptom-defined GERD was 3.1% and varied significantly (<it>p </it>< 0.001) among the five regions (from 1.7% in Guangzhou to 5.1% in Wuhan) and between rural and urban populations (3.8% vs 2.4%). Factors significantly associated with GERD included living in a rural area and a family history of gastrointestinal diseases.</p> <p>Conclusions</p> <p>This population-based survey found that the prevalence of symptom-defined GERD in China was 3.1%, which is lower than that found in Western countries.</p

Crohn's Disease and Early Exposure to Domestic Refrigeration

Environmental risk factors playing a causative role in Crohn's Disease (CD) remain largely unknown. Recently, it has been suggested that refrigerated food could be involved in disease development. We thus conducted a pilot case control study to explore the association of CD with the exposure to domestic refrigeration in childhood.Using a standard questionnaire we interviewed 199 CD cases and 207 age-matched patients with irritable bowel syndrome (IBS) as controls. Cases and controls were followed by the same gastroenterologists of tertiary referral clinics in Tehran, Iran. The questionnaire focused on the date of the first acquisition of home refrigerator and freezer. Data were analysed by a multivariate logistic model. The current age was in average 34 years in CD cases and the percentage of females in the case and control groups were respectively 48.3% and 63.7%. Patients were exposed earlier than controls to the refrigerator (X2 = 9.9, df = 3, P = 0.04) and refrigerator exposure at birth was found to be a risk factor for CD (OR = 2.08 (95% CI: 1.01-4.29), P = 0.05). Comparable results were obtained looking for the exposure to freezer at home. Finally, among the other recorded items reflecting the hygiene and comfort at home, we also found personal television, car and washing machine associated with CD.This study supports the opinion that CD is associated with exposure to domestic refrigeration, among other household factors, during childhood

The global, regional, and national burden of gastro-oesophageal reflux disease in 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017

Background Gastro-oesophageal reflux disease is a common chronic ailment that causes uncomfortable symptoms and increases the risk of oesophageal adenocarcinoma. We aimed to report the burden of gastro-oesophageal reflux disease in 195 countries and territories between 1990 and 2017, using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017. Methods We did a systematic review to identify measurements of the prevalence of gastro-oesophageal reflux disease in geographically defined populations worldwide between 1990 and 2017. These estimates were analysed with DisMod-MR, a Bayesian mixed-effects meta-regression tool that incorporates predictive covariates and adjustments for differences in study design in a geographical cascade of models. Fitted values for broader geographical units inform prior distributions for finer geographical units. Prevalence was estimated for 195 countries and territories. Reports of the frequency and severity of symptoms among individuals with gastro-oesophageal reflux disease were used to estimate the prevalence of cases with no, mild to moderate, or severe to very severe symptoms at a given time; these estimates were multiplied by disability weights to estimate years lived with disability (YLD). Findings Data to estimate gastro-oesophageal reflux disease burden were scant, totalling 144 location-years (unique measurements from a year and location, regardless of whether a study reported them alongside measurements for other locations or years) of prevalence data. These came from six (86%) of seven GBD super-regions, 11 (52%) of 21 GBD regions, and 39 (20%) of 195 countries and territories. Mean estimates of age-standardised prevalence for all locations in 2017 ranged from 4408 cases per 100 000 population to 14 035 cases per 100 000 population. Age-standardised prevalence was highest (>11 000 cases per 100 000 population) in the USA, Italy, Greece, New Zealand, and several countries in Latin America and the Caribbean, north Africa and the Middle East, and eastern Europe; it was lowest (<7000 cases per 100 000 population) in the high-income Asia Pacific, east Asia, Iceland, France, Denmark, and Switzerland. Global prevalence peaked at ages 75–79 years, at 18 820 (95% uncertainty interval [95% UI] 13 770–24 000) cases per 100 000 population. Global age-standardised prevalence was stable between 1990 and 2017 (8791 [95% UI 7772–9834] cases per 100 000 population in 1990 and 8819 [7781–9863] cases per 100 000 population in 2017, percentage change 0·3% [–0·3 to 0·9]), but all-age prevalence increased by 18·1% (15·6–20·4) between 1990 and 2017, from 7859 (6905–8851) cases per 100  000 population in 1990 to 9283 (8189–10 400) cases per 100  000 population in 2017. YLDs increased by 67·1% (95% UI 63·5–70·3) between 1990 and 2017, from 3·60 million (1·93–6·12) in 1990 to 6·01 million (3·22–10·19) in 2017. Interpretation Gastro-oesophageal reflux disease is common worldwide, although less so in much of eastern Asia. The stability of our global age-standardised prevalence estimates over time suggests that the epidemiology of the disease has not changed, but the estimates of all-age prevalence and YLDs, which increased between 1990 and 2017, suggest that the burden of gastro-oesophageal reflux disease is nonetheless increasing as a result of ageing and population growth. Funding Bill & Melinda Gates Foundation