Antireflux Surgery Versus Antireflux Medication and Risk of Esophageal Adenocarcinoma in Patients With Barrett's Esophagus.

BACKGROUND & AIMS: Antireflux treatment is recommended to reduce esophageal adenocarcinoma in patients with Barrett's esophagus. Antireflux surgery (fundoplication) counteracts gastroesophageal reflux of all types of carcinogenic gastric content and reduces esophageal acid exposure to a greater extent than antireflux medication (eg, proton pump inhibitors). We examined the hypothesis that antireflux surgery prevents esophageal adenocarcinoma to a larger degree than antireflux medication in patients with Barrett's esophagus. METHODS: This multinational and population-based cohort study included all patients with a diagnosis of Barrett's esophagus in any of the national patient registries in Denmark (2012-2020), Finland (1987-1996 and 2010-2020), Norway (2008-2020), or Sweden (2006-2020). Patients who underwent antireflux surgery were compared with nonoperated patients using antireflux medication. The risk of esophageal adenocarcinoma was calculated using multivariable Cox regression, providing hazard ratios (HRs) and 95% CIs adjusted for age, sex, country, calendar year, and comorbidity. RESULTS: The cohort consisted of 33,939 patients with Barrett's esophagus. Of these, 542 (1.6%) had undergone antireflux surgery. During up to 32 years of follow-up, the overall HR was not decreased in patients having undergone antireflux surgery compared with nonoperated patients using antireflux medication, but rather increased (adjusted HR, 1.9; 95% CI, 1.1-3.5). In addition, HRs did not decrease with longer follow-up, but instead increased for each follow-up category, from 1.8 (95% CI, 0.6-5.0) within 1-4 years of follow-up to 4.4 (95% CI, 1.4-13.5) after 10-32 years of follow-up. CONCLUSIONS: Patients with Barrett's esophagus who undergo antireflux surgery do not seem to have a lower risk of esophageal adenocarcinoma than those using antireflux medication.

Esophageal cancer in China: Practice and research in the new era.

China, as the one of the largest developing countries in the world and with about one-fifth of the global population, is bearing an increasing burden on health from cancer. In the area of esophageal cancer (EC), China accounts for more than 50% of the global cases, with this disease being a particularly worse for those in disadvantaged populations. Along with China's socioeconomic condition, the epidemiology, diagnosis, therapeutics and research of EC have developed throughout the 21st century. In the current review, existing control measures for EC in China are outlined, including the incidence, mortality, screening, clinical diagnosis, multidisciplinary treatment and research landscape. EC in China are very different from those in some other parts of the world, especially in Western countries. Core measures that could contribute to the prevention of EC and improve clinical outcomes in patients of less developed countries and beyond are recommended. International cooperation among academia, government and industry is especially warranted in global EC control.

Missed opportunities to screen for Barrett's esophagus in the primary care setting of a large health system.

BACKGROUND AND AIMS: The rate of esophageal adenocarcinoma (EAC) is rising. This is partly due to the lack of identification of Barrett's esophagus (BE), the main risk factor for EAC. Identifying neoplastic BE can allow for endoscopic therapy to prevent EAC. Our aim was to determine how many patients eligible for screening are actually being screened for BE in the primary care setting of a large health system. METHODS: A digital search algorithm was constructed using the established gastroenterology guidelines and the Kunzmann model for screening for BE. The algorithm was then applied to the electronic medical record of all patients seen in the primary care setting of the health system. A manual review of charts of the identified patients was performed to confirm the high-risk status and determine if screening occurred. RESULTS: Of 936,371 primary care charts analyzed by the algorithm, 3535 patients (.4%) were determined to be high-risk for BE. Of these 3535 patients, only 1077 (30%) were screened for BE in clinical practice with endoscopy. The algorithm identified 2458 (70%) additional high-risk patients. Of the patients screened in clinical practice, 105 (10%) were found to have BE (10% with neoplasia). CONCLUSIONS: Numerous screening opportunities for BE are missed in the primary care setting of a large health system. Collaboration between gastroenterology and primary care services is needed to improve the screening rate.

Climate Change and the Esophagus: Speculations on Changing Disease Patterns as the World Warms.

PURPOSE OF REVIEW: Esophageal disorders, including gastroesophageal reflux disease (GERD), eosinophilic esophagitis (EoE), and esophageal cancer, may be affected by climate change. Our review describes the impact of climate change on risk factors associated with esophageal diseases and speculates how these climate-related factors impacted esophageal disorders and their management. RECENT FINDINGS: Climate change is responsible for extreme weather conditions (shifts in rainfall, floods, droughts, and forest fires) and global warming. These consequences affect basic human needs of water and food, causing changes in population dynamics and pose significant threats to digestive health, including common esophageal disorders like GERD, EoE, and esophageal cancers. The changing patterns of esophageal diseases with climate change are likely mediated through risk factors, including nutrition, pollutants, microplastics, and the microbiota-gut-brain axis. The healthcare process itself, including GI endoscopy practices commonly employed in diagnosing and therapeutics of esophageal diseases, may, in turn, contribute to climate change through plastic wastage and greenhouse gas emissions, thus creating the climate change lifecycle. Breaking the cycle would involve changes at the individual level, community level, and national policy level. Prevention is key, with individuals identifying and remediating risk factors and reducing carbon footprints. The ABC (Advocacy, Broadcast, and Collaborate) activities would help enhance awareness at the community level. Higher-level programs such as the Bracing Resilience Against Climate Effects (BRACE) would lead to broader and larger-scale adoption of public health adaptation strategies at the national level. The impact of climate change on esophageal disorders is likely real, mediated by several risk factors, and creates a climate change lifecycle that may only break if changes are made at individual, community, and national levels.

Revisiting Proton Pump Inhibitors as Chemoprophylaxis Against the Progression of Barrett's Esophagus.

PURPOSE OF REVIEW: Barrett's esophagus (BE) is associated with chronic gastroesophageal reflux disease and is a known precursor to esophageal adenocarcinoma. While endoscopic surveillance strategies and the role for endoscopic eradication therapy have been well established, there has been much interest in identifying chemopreventive agents to disrupt or halt the metaplasia-dysplasia-carcinoma sequence in patients with BE. RECENT FINDINGS: No pharmacological agent has held more hope in reducing the risk of neoplastic progression in BE than proton pump inhibitors (PPIs). However, data supporting PPIs for chemoprevention have largely been from observational cohort and case-control studies with mixed results. In this review, we revisit the literature and highlight the role of PPIs in patients with BE as it pertains to chemoprophylaxis against the progression of BE to dysplasia and esophageal adenocarcinoma.

Abrogation of esophageal carcinoma development in miR-31 knockout rats.

MicroRNA-31 (miR-31) is overexpressed in esophageal squamous cell carcinoma (ESCC), a deadly disease associated with dietary Zn deficiency and inflammation. In a Zn deficiency-promoted rat ESCC model with miR-31 up-regulation, cancer-associated inflammation, and a high ESCC burden following N-nitrosomethylbenzylamine (NMBA) exposure, systemic antimiR-31 delivery reduced ESCC incidence from 85 to 45% (P = 0.038) and miR-31 gene knockout abrogated development of ESCC (P = 1 × 10-6). Transcriptomics, genome sequencing, and metabolomics analyses in these Zn-deficient rats revealed the molecular basis of ESCC abrogation by miR-31 knockout. Our identification of EGLN3, a known negative regulator of nuclear factor κB (NF-κB), as a direct target of miR-31 establishes a functional link between oncomiR-31, tumor suppressor target EGLN3, and up-regulated NF-κB-controlled inflammation signaling. Interaction among oncogenic miR-31, EGLN3 down-regulation, and inflammation was also documented in human ESCCs. miR-31 deletion resulted in suppression of miR-31-associated EGLN3/NF-κB-controlled inflammatory pathways. ESCC-free, Zn-deficient miR-31-/- rat esophagus displayed no genome instability and limited metabolic activity changes vs. the pronounced mutational burden and ESCC-associated metabolic changes of Zn-deficient wild-type rats. These results provide conclusive evidence that miR-31 expression is necessary for ESCC development.

The Protease Inhibitor Amprenavir Protects against Pepsin-Induced Esophageal Epithelial Barrier Disruption and Cancer-Associated Changes.

Gastroesophageal reflux disease (GERD) significantly impacts patient quality of life and is a major risk factor for the development of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). Proton pump inhibitors (PPIs) are the standard-of-care for GERD and are among the most prescribed drugs in the world, but do not protect against nonacid components of reflux such as pepsin, or prevent reflux-associated carcinogenesis. We recently identified an HIV protease inhibitor amprenavir that inhibits pepsin and demonstrated the antireflux therapeutic potential of its prodrug fosamprenavir in a mouse model of laryngopharyngeal reflux. In this study, we assessed the capacity of amprenavir to protect against esophageal epithelial barrier disruption in vitro and related molecular events, E-cadherin cleavage, and matrix metalloproteinase induction, which are associated with GERD severity and esophageal cancer. Herein, weakly acidified pepsin (though not acid alone) caused cell dissociation accompanied by regulated intramembrane proteolysis of E-cadherin. Soluble E-cadherin responsive matrix metalloproteinases (MMPs) were transcriptionally upregulated 24 h post-treatment. Amprenavir, at serum concentrations achievable given the manufacturer-recommended dose of fosamprenavir, protected against pepsin-induced cell dissociation, E-cadherin cleavage, and MMP induction. These results support a potential therapeutic role for amprenavir in GERD recalcitrant to PPI therapy and for preventing GERD-associated neoplastic changes.

Quality of Online Information for Esophageal Cancer.

The Internet is a readily available source of information, and patients in North America frequently access it. Esophageal cancer is the 7th most common cancer worldwide, but there is a lack of studies examining esophageal cancer website quality. This current study looks to systematically analyze the quality of websites accessed by patients with esophageal cancer. A previously validated website evaluation tool was used to analyze the quality of online esophageal cancer resources for patients. The term "esophagus cancer" was used to retrieve hits from the search engine Google and the meta-search engines Dogpile and Yippy. A 100 website list was compiled using pre-specified inclusion and exclusion criteria. Websites were evaluated regarding administration, accountability, authorship, organization, readability, content, and accuracy. The term "esophagus cancer" returned over 500 websites from the search engines. Of the 100 websites included for analysis, 97% disclosed ownership, sponsorship, and advertising. Only 35% identified an author and even fewer (31%) gave the author's credentials. Only 31% declared updates to their information within the past 2 years. Readability scores revealed only 9%, and 12% of sites scored at an elementary level, according to the Flesch-Kincaid (FK) and SMOG scoring scales, respectively. The average FK and SMOG scores were 12.6 and 11.0, respectively. Detection was the most accurately described (70%). However, few websites provided accurate incidence/prevalence (28%), stage-specific prognosis (27%), or preventative information (17%). The quality of websites offering information on esophageal cancer is variable. While they overwhelmingly disclose website ownership interests, most do not identify authors, poorly describe important domains of esophageal cancer, and overall readability exceeds the commonly accepted level for non-healthcare professionals.

Gastroesophageal Reflux Disease Is Not a Great Screening Criterion: Time to Move on to Other Strategies for Controlling the Burden of Esophageal Adenocarcinoma.

ABSTRACT: Gastroesophageal reflux disease (GERD) is key in the pathogenesis of Barrett's esophagus and esophageal adenocarcinoma (EAC). Endoscopic screening of select individuals with GERD symptoms for Barrett's esophagus and EAC has been recommended, but the great majority of patients with EAC had never undergone prior screening, despite over a million esophagogastroduodenoscopies (EGDs) performed annually in the United States among individuals with GERD symptoms. This is likely due to a conflation among providers regarding diagnostic EGD in those with refractory symptoms and screening EGD. An alternative approach is needed that de-emphasizes GERD to avoid confusion and increase uptake of appropriate screening.

The Association between Dietary Vitamin C Intake and the Risk of Esophageal Cancer: An Updated Dose-Response Meta-Analysis.

Although some epidemiological studies have reported the associations between vitamin C and risk of esophageal cancer, these results are inconsistent. Therefore, we performed an updated meta-analysis to explore the associations between dietary vitamin C intake and risk of esophageal cancer. We used PubMed, Embase, and the Web of Science to screen all published articles, which yielded 18 papers eligible for data extraction (involving 4,126 cases and 36,902 controls), and then pooled the odds ratios (ORs) and corresponding 95% confidence intervals (CIs) using random-effects model. As we detected the associations in highest category and the lowest type of dietary vitamin C intake, we discovered that dietary vitamin C intake was negatively correlated to the risk of esophageal cancer. The analysis of subgroup showed a significant counter proportion between vitamin C and the risk of ESCC and EAC. Moreover, the dose-analysis indicated that if increasing dietary intake of vitamin C of 50 mg/day, esophageal cancer risk dropped down 10% (OR = 0.81, 95%CI: 0.75-0.87). In summary, our study provides a comprehensive and updated epidemiological evidence to elucidate the relationships between dietary vitamin C and reduction of esophageal cancer risk. Nevertheless, we still need larger case-control and cohort studies to confirm these connections.

Epidemiology and prevention of oesophageal adenocarcinoma.

Oesophageal adenocarcinoma (OAC) develops from columnar metaplasia of the distal oesophagus, Barrett's oesophagus (BO), secondary to chronic gastro-oesophageal reflux disease (GORD). In the present review, the stepwise development of GORD, BO and OAC is presented and the evidence of OAC prevention, including treatment with proton pump inhibitors (PPIs). PPIs are the main treatment of GORD and BO, with some evidence of prevention of OAC in these patients. However, as about 40% of OAC patient do not report a history of GORD and fewer than 15% of OAC cases are detected in individuals during BO surveillance, prevention of OAC is limited by PPI use in GORD and BO patients.

The impact of a healthy lifestyle on the risk of esophageal and gastric cancer subtypes.

Few prospective studies have been conducted on a combined healthy lifestyle and risk of esophageal and gastric cancer, and even less on subtypes: esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), gastric cardia adenocarcinoma (GCA), and gastric non-cardia adenocarcinoma (GNCA). The relationship of a healthy lifestyle score (HLS) with risk of these cancers was investigated in the Netherlands Cohort Study. In 1986, 120,852 men and women aged 55-69 years provided information on dietary and lifestyle habits. The HLS was derived from information on smoking, body mass index, physical activity, Mediterranean diet adherence, and alcohol intake. After 20.3 years of follow-up, multivariable case-cohort analyses were based on 333 incident esophageal and 777 gastric cancer cases, and 3720 subcohort members with complete data on lifestyles and confounders. The impact of changing to healthy lifestyles was estimated with the rate advancement period (RAP). The HLS was significantly inversely associated with risk of esophageal and gastric cancer, and subtypes (except EAC), in a linear fashion. The observed HR decrease per 1-point increase in HLS was 31% for esophageal, and 19% for gastric cancer, 49% for ESCC, 23% for GCA, and 18% for GNCA. The RAP per 1-point increase in HLS ranged from - 11.75 years for ESCC to - 2.85 years for GNCA. Also after excluding smoking, inverse associations between the HLS and esophageal and gastric cancer risk were still apparent. These results suggest that adhering to a combination of healthy modifiable lifestyle factors may substantially reduce the risk of esophageal and gastric cancer.

Need for improvement in the evaluation of pre-malignant upper gastro-intestinal lesions in India: Results of a nationwide survey.

BACKGROUND AND AIM: Gastric and esophageal cancers are associated with high morbidity in India. In the absence of formal screening programs in India, it is essential that all elective esophago-gastro-duodenoscopies (EGDs), irrespective of indication, be also considered an opportunity to screen for premalignant lesions. With this premise, we tried to assess the adherence to best practices in the detection of premalignant upper gastro-intestinal lesions (PMUGIL) among endoscopists in India. We also evaluated the adequacy of training, availability of appropriate facilities, and differences between teaching and non-teaching centers. METHODS: We disbursed a survey among endoscopists working in India, through the membership database of the Society of Gastrointestinal Endoscopists of India, by email and instant messaging. The responses were collected and subsequently analyzed. RESULTS: We obtained a total of 422 eligible responses. The adherence to best practices assessed was lower than the set threshold in all except one parameter in both teaching centers and non-teaching centers. Only 58.5% of endoscopists had received training in the detection of PMUGIL. Appropriate image enhanced endoscopy (IEE) facilities were available to only 58.05% of surveyed endoscopists. CONCLUSIONS: Strategies to improve detection of PMUGIL should be directed at improving adherence to best practices, ensuring adequate training of endoscopists in the evaluation of PMUGIL and improving infrastructure.

Chemoprevention of Oesophageal Squamous-Cell Carcinoma and Adenocarcinoma: A Multicentre Retrospective Cohort Study.

BACKGROUND: Oesophageal cancer comprises 2 different histological variants: oesophageal squamous-cell carcinoma (ESCC) and adenocarcinoma (EAC). While there are multiple therapeutic options for both types, patients with advanced or metastatic oesophageal cancer still suffer from poor prognosis. AIMS: The study aimed to examine the association between the risk of oesophageal cancer and medications and to estimate the chemopreventive effects of commonly used drugs. METHODS: A multicentre retrospective cohort study was conducted using data from 9 hospital databases of hospitalized patients between 2014 and 2019. The primary outcomes were ESCC and EAC. The association of oesophageal cancer with drug use and clinical factors was evaluated. Odds ratios (ORs) were adjusted for age, sex, Charlson comorbidity index scores, and smoking with/without gastro-oesophageal reflux disease. RESULTS: The use of proton pump inhibitors (PPIs) (adjusted OR [aOR] 0.48, p < 0.0001), aspirin (aOR 0.32, p < 0.0001), cyclooxygenase-2 inhibitor (COX2I) (aOR 0.70, p = 0.0005), steroid (aOR 0.19, p < 0.0001), statin (aOR 0.43, p < 0.0001), and metformin (aOR 0.42, p < 0.0001) was associated with a lower risk of ESCC than that in non-use. The use of aspirin (aOR 0.33, p = 0.0006) and steroids (aOR 0.54, p = 0.022) was associated with a lower risk of EAC than that in non-use. CONCLUSION: COX2Is, statins, metformin, and PPIs could help in prevention of ESCC, and aspirin and steroids may be chemopreventive for both types of oesophageal cancer.

Outcomes of Radiofrequency Ablation Compared to Liquid Nitrogen Spray Cryotherapy for the Eradication of Dysplasia in Barrett's Esophagus.

INTRODUCTION: Current guidelines recommend endoscopic eradication therapy (EET) for Barrett's esophagus (BE) with dysplasia and intramucosal adenocarcinoma using either radiofrequency ablation (RFA) or liquid nitrogen spray cryotherapy (LNSC). The aims of this multicenter study are to compare the rate and number of treatment sessions of RFA vs. LNSC to achieve CE-D and CE-IM and assess outcomes for those who switched therapy. METHODS: This is a retrospective cohort study of patients with BE undergoing EET. Demographics, baseline variables, endoscopy details, and histology information were abstracted. RESULTS: One hundred and sixty-two patients were included in this study with 100 patients in the RFA group and 62 patients in the LNSC group. The rate of CE-D and CE-IM did not differ between the RFA group and LNSC group (81% vs. 71.0%, p = 0.14) and (64% vs. 66%, p = 0.78), respectively. The number of sessions to achieve CE-D and CE-IM was higher with LNSC compared to RFA (4.2 vs. 3.2, p = 0.05) and (4.8 vs. 3.5, p = 0.04), respectively. The likelihood of developing recurrent dysplasia was higher among patients who did not achieve CE-IM (12%) compared to those who did achieve CE-IM (4%), p = 0.04. Similar findings were found in those who switched treatment modalities. DISCUSSION: EET is highly effective in eradication of Barrett's associated dysplasia and neoplasia. Both RFA and LNSC achieved similar rates of CE-D and CE-IM although LNSC required more sessions. Also, achievement of CE-IM was associated with less recurrence rates of dysplasia.

Dietary intake of monounsaturated and polyunsaturated fatty acids is related to the reduced risk of esophageal squamous cell carcinoma.

BACKGROUND: The relationship of consumption of dietary fat and fatty acids with esophageal squamous cell carcinoma (ESCC) risk remains unclear. This study aimed to explore the relationship of dietary fat and fatty acids intake with ESCC risk. METHODS: This case-control study included 879 incident cases and 892 community-based controls recruited from Southwest China. A food frequency questionnaire was adopted to collect information about dietary information, and intake of fat, saturated fatty acid (SFA), monounsaturated fatty acid (MUFA), polyunsaturated fatty acid (PUFA), and total fatty acid (TFA) was calculated. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were estimated using the logistic regression model. RESULTS: When comparing the highest with lowest intake quintiles, MUFA (OR: 0.33, 95% CI: 0.21-0.51), PUFA (OR: 0.32, 95% CI: 0.20-0.51), and TFA (OR: 0.44, 95% CI: 0.28-0.70) were related to a reduced risk of ESCC after adjusting for confounders; for non-drinkers rather than drinkers, the intake of SFA was significantly related to a 61% (OR: 0.39, 95% CI: 0.19-0.81) reduced risk of ESCC when comparing the highest with the lowest intake quintiles. Dietary fat was not related to the risk of ESCC. CONCLUSIONS: This study suggested that the more intake of MUFA and PUFA, the lower risk of ESCC, whereas the protective effect of TFA was only observed among non-drinkers. Strategic nutritional programs should consider food rich in unsaturated fatty acids to mitigate the occurrence of ESCC.

Laparoscopic total fundoplication is superior to medical treatment for reducing the cancer risk in Barrett's esophagus: a long-term analysis.

The present study aims to compare the effectiveness of surgical and medical therapy in reducing the risk of cancer in Barrett's esophagus in a long-term evaluation. A prospective cohort was designed that compared Barrett's esophagus patients submitted to medical treatment with omeprazole or laparoscopic Nissen fundoplication. The groups were compared using propensity score matching paired by Barrett's esophagus length. A total of 398 patients met inclusion criteria. There were 207 patients in the omeprazole group (Group A) and 191 in the total fundoplication group (Group B). After applying the propensity score matching paired by Barrett's esophagus length, the groups were 180 (Group A) and 190 (Group B). Median follow-up was 80 months. Group B was significantly superior for controlling GERD symptoms. Group B was more efficient than Group A in promoting Barrett's esophagus regression or blocking its progression. Group B was more efficient than Group A in preventing the development of dysplasia and cancer. Logistic regression was performed for the outcomes of adenocarcinoma and dysplasia. Age and body mass index were used as covariates in the logistic regression models. Even after regression analysis, Group B was still superior to Group A to prevent esophageal adenocarcinoma or dysplasia transformation (odds ratio [OR]: 0.51; 95% confidence interval [CI]: 0.27-0.97, for adenocarcinoma or any dysplasia; and OR: 0.26; 95% CI: 0.08-0.81, for adenocarcinoma or high-grade dysplasia). Surgical treatment is superior to medical management, allowing for better symptom control, less need for reflux medication use, higher regression rate of the columnar epithelium and intestinal metaplasia, and lower risk for progression to dysplasia and cancer.

Inhibition of the BMP pathway prevents development of Barrett's-associated adenocarcinoma in a surgical rat model.

INTRODUCTION: Esophageal adenocarcinoma (EAC) is an aggressive cancer, associated with reflux esophagitis and intestinal metaplasia (IM). One underlying biological mechanism, which possibly drives the development of EAC, is the dysregulated expression of Bone Morphogenetic Proteins (BMPs). AIM: To investigate if local delivery of Noggin, a BMP antagonist, reduced EAC. METHODS: After obtaining proof of principal on local delivery of a Noggin/Sucralfate substance, a randomized controlled trial to test the effects of Noggin on EAC development was performed in a surgical rat model. In the model, an esophago-jejunostomy leads to development of reflux-esophagitis, IM and eventually EAC. Rats were treated by Noggin/Sucralfate or Sucralfate alone. Treatment was administered from 26 to 29 weeks after the operation. RESULTS: Of the 112 operated rats, 52 survived beyond 26 weeks. Finally, 25 rats treated with Noggin/Sucralfate and 21 with Sucralfate, were evaluated. At the end, 39 (85%) of the animals had IM while 28 (61%) developed cancer. There were significantly more cancers in the Noggin/Sucralfate arm (50%) versus the Sucralfate group (73%) (Chi square, P < 0.05). Most cancers were mucous producing T3 adenocarcinomas. There were no significant differences in the amount of IM, size or grade of the cancers, or expression of columnar and squamous markers between the two groups. CONCLUSION: In this study, we demonstrated that inhibition of BMPs by Noggin reduced development of EAC in a surgical esophagitis-IM-EAC rat model. In future, effective targeting of the BMP pathway with selective BMP-inhibitors could become an important asset to improve EAC patient outcome.

Is metformin use associated with a reduced risk of oesophageal cancer? A systematic review and meta-analysis.

OBJECTIVES: Studies on the association between metformin use and the risk of oesophageal cancer (OC) have generated controversial findings. This updated meta-analysis was conducted to reassess the effects of metformin on OC. METHODS: A comprehensive search strategy was conducted to select relevant studies from origination to February 2021. Heterogeneity was evaluated through the Q test and I2 statistics. HRs and 95% CIs were pooled through either random-effect or fixed-effect models. Meta-regression, subgroup analyses, sensitivity analysis and publication bias diagnosis were also performed. RESULTS: Seven studies with 5 426 343 subjects were included. Metformin use was associated with reduced risk of OC (HR=0.69, 95% CI 0.54 to 0.87, p<0.001). Sensitivity analysis suggested that the results were relatively stable. CONCLUSION: Metformin is associated with a reduced risk of OC. More well-designed studies are still needed to further elaborate on these associations. PROSPERO REGISTRATION NUMBER: CRD42021237127.

Barrett Esophagus: Rapid Evidence Review.

Barrett esophagus is a premalignant change of the esophagus; however, malignant transformation to esophageal adenocarcinoma is rare in patients without dysplasia. Barrett esophagus is estimated to affect up to 5.6% of the U.S. population. Risk factors for Barrett esophagus include gastroesophageal reflux disease, obesity, age older than 50 years, male sex, tobacco use, and a family history of Barrett esophagus or esophageal adenocarcinoma. Patients who experience chronic gastroesophageal reflux symptoms plus additional risk factors should be considered for screening. Mucosal change consistent with Barrett esophagus is visualized during upper endoscopy; biopsy confirms the diagnosis and determines if dysplasia is present. Management of Barrett esophagus depends on the presence and severity of dysplasia; endoscopic treatment of dysplasia decreases the risk of malignant transformation. Surveillance after diagnosis is recommended to monitor for dysplasia and diagnose and treat esophageal adenocarcinoma at an earlier stage. Patients with Barrett esophagus should be offered proton pump inhibitor therapy to control reflux symptoms and possibly decrease the risk of developing esophageal adenocarcinoma. Statins, nonsteroidal anti-inflammatory drugs, and aspirin are associated with a decreased risk of esophageal adenocarcinoma in patients with Barrett esophagus; however, they should not generally be prescribed in the absence of another indication. Mortality benefits of screening and surveillance are uncertain.