Esophageal Adenocarcinoma In Patients Research Articles

Helicobacter pylori infection does not influence the progression from gastroesophageal reflux disease to Barrett's esophagus to esophageal adenocarcinoma.

We conducted a meta-analysis evaluating the overall risk of esophageal adenocarcinoma (EAC) in individuals with Helicobacter pylori infection, and a network meta-analysis to assess the role of H. pylori infection in the progression from Barrett's esophagus (BE) to EAC. The MEDLINE, EMBASE and Cochrane databases were searched between 1988 and June 2023 for observational studies of H. pylori infection and the risk of EAC. Summary odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using the DerSimonian-Laird method. I2 statistics were calculated to examine heterogeneity. Thirteen studies were included in the meta-analysis and 3 additional studies were included in the network meta-analysis. For comparisons with controls, individuals with H. pylori infection were 46% less likely to develop EAC than individuals without H. pylori infection (OR, 0.54; 95% CI: 0.46, 0.64), with low heterogeneity between studies (I2=4.4%). The magnitude of the inverse association was stronger in the two large cohort studies (OR=0.31) than in the 11 case-control studies (OR=0.55). When comparing to controls, the network meta-analysis of 6 studies showed that H. pylori infection was associated with a lower risk of GERD (OR=0.68) or BE (OR=0.59) or EAC (OR=0.54); however, H. pylori infection was not associated with risk of EAC in patients with BE (OR=0.91; 95% CI: 0.68, 1.21). This meta-analysis provides the strongest evidence yet that H. pylori infection is inversely associated with EAC. H. pylori does not appear to be associated with BE progression to EAC.

Risk of Esophageal Adenocarcinoma After Bariatric Surgery: A Meta-Analysis of Retrospective Studies.

This study aims to systematically review and meta-analyze the evidence on the risk of esophageal adenocarcinoma (EAC) following metabolic and bariatric surgery (MBS). A systematic literature search was conducted on the China National Knowledge Infrastructure (CNKI), Wanfang, EMBASE, MEDLINE, Web of Science, The Cochrane Library, and PubMed databases. Meta-analysis utilized odds ratios (ORs) and 95% confidence intervals (CIs) to analyze the correlation between MBS and the risk of EAC. Meta-analysis was performed using STATA software (version 12.0). Fourteen studies involving patients with obesity undergoing bariatric surgery and control groups receiving conventional treatment were included. The meta-analysis indicated a reduction in the overall incidence of esophageal cancer after bariatric surgery (OR = 0.69, 95% CI: 0.51-0.95, P = 0.022). Subgroup analysis results demonstrated a decreased risk of EAC in European patients with obesity undergoing MBS treatment (OR: 0.60, 95% CI: 0.38-0.95, P = 0.028). In studies with a sample size greater than or equal to 100,000 patients, the risk of EAC in patients with obesity undergoing MBS was significantly lower than the non-surgery group (OR: 0.59, 95% CI: 0.42-0.83, P = 0.003). Articles published before 2020 and those published in 2020 or earlier showed a significant difference in the incidence of EAC between the surgery and non-surgery groups (OR: 0.57, 95% CI: 0.43-0.75, P < 0.001). The risk of EAC in patients with obesity with a follow-up time of less than 5years was statistically significant (OR: 0.46, 95% CI: 0.25-0.82, P = 0.009). Our meta-analysis results suggest a reduced risk of esophageal cancer in patients with obesity after bariatric surgery. CRD 42024505177.

Abstract 6184: A novel approach to Barrett's esophagus risk stratification: Whole-slide image analysis for aneuploidy detection

Abstract Background Barrett’s esophagus (BE) is the only known precursor of esophageal adenocarcinoma (EAC) and there is a need for biomarkers in BE for risk stratification for cancer progression. Aneuploidy has been suggested as a factor in the development, initiation or progression of EAC in patients with BE, and it has been found predictive for EAC progression (Hadjinicolaou, et al. 2020, Sikkema, et al. 2009). However, current assays for detecting aneuploidy require valuable tissue, hence validation studies are limited. We hypothesise that routine histology images can be used to detect ploidy status. We aim to develop a sensitive, accurate, and easy-to-use deep learning tool for this purpose. Methods We used a weakly supervised deep learning-based approach called clustering-constrained-attention multiple-instance learning (CLAM) (Lu et al., 2021) to detect aneuploidy on hematoxylin and eosin-stained whole slide images of endoscopical biopsies from BE, for which the ploidy status had been determined by flow cytometry. To benchmark the model’s performance, we also trained a traditional fully supervised algorithm, ResNet50 (He et al., 2016), with the same dataset. The models were trained on 388 slides (51 aneuploid) from the Seattle Barrett’s Esophagus Annotated Resource (BEAR) and then applied to an independent test cohort of BEAR patients, consisting of 279 slides (36 aneuploid). Results The multi-attention-branch CLAM model achieved AUC of 0.82 and 76.4% balanced accuracy for aneuploidy on the internal test subset (10% of the cohort). On the independent test dataset, the model achieved AUC of 0.85 and 79.3% balanced accuracy, while performance of the fully supervised model was AUC of 0.65 and 33.1 balanced accuracy. In a challenging subset for image-based diagnosis, including 253 samples (29 aneuploid) without dysplasia or atypical mitosis (a major feature of aneuploidy samples) the model achieved a 67.6% accuracy and an AUC of 0.83. Both the flow results (p=2.84e-7) and the model's predictions (p=2.18e-3) revealed a correlation between progression to EAC and ploidy status. Conclusion We developed a deep learning model for predicting aneuploidy in BE biopsies. The weakly-supervised approach can perform much better compared to the traditional fully-supervised model. Aneuploidy is correlated with cancer progression and stands as a promising candidate for the prediction of cancer progression in BE patients. Although atypical mitosis is the primary histological indicator of aneuploidy, our model can still make aneuploid predictions in the absence of atypical mitosis, as it doesn't rely solely on a single parameter. Our model is efficient, capable of processing hundreds of samples resource-effectively, and thus an ideal adjunct to standard histologic evaluation. This classifier may facilitate molecular-based improvements in identifying individuals at high risk of progression. Citation Format: Caner Ercan, Xiaoxi Pan, Thomas G. Paulson, Matthew D. Stachler, Carlo C. Maley, Yinyin Yuan. A novel approach to Barrett's esophagus risk stratification: Whole-slide image analysis for aneuploidy detection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6184.

Treatment of esophageal adenocarcinoma in patients with a history of bariatric surgery

The relationship among obesity, bariatric surgery, and esophageal adenocarcinoma (EAC) is complex, given that some bariatric procedures are thought to be associated with increased incidence of reflux and Barrett's esophagus. Previous bariatric surgery may complicate the use of the stomach as a conduit for esophagectomy. In this study, we presented our experience with patients who developed EAC after bariatric surgery and described the challenges encountered and the techniques used. We conducted a retrospective review of our institutional database to identify all patients at our institution who were treated for EAC after previously undergoing bariatric surgery. In total, 19 patients underwent resection with curative intent for EAC after bariatric surgery, including 10 patients who underwent sleeve gastrectomy. The median age at diagnosis of EAC was 63 years; patients who underwent sleeve gastrectomy were younger (median age, 56 years). The median time from bariatric surgery to EAC was 7 years. Most patients had a body mass index (BMI) score of >30kg/m2 at the time of diagnosis of EAC; approximately 40% had class III obesity (BMI score > 40kg/m2). Six patients (32%) had known Barrett's esophagus before undergoing a reflux-increasing bariatric procedure. Sleeve gastrectomy patients underwent esophagectomy with gastric conduit, colonic interposition, or esophagojejunostomy. Only 1 patient had an anastomotic leak (after esophagojejunostomy). Endoscopy should be required both before (for treatment selection) and after all bariatric surgical procedures. Resection of EAC after bariatric surgery requires a highly individualized approach but is safe and feasible.

Incidence rates of Barrett’s esophagus and esophageal adenocarcinoma: a systematic review and meta-analysis

Background and AimsBarrett’s esophagus (BE) surveillance is commonly performed to detect early dysplasia and esophageal adenocarcinoma (EAC). However, high-quality incidence rates for the development of dysplasia and EAC in patients with BE are limited. This study aims to perform a systematic review and meta-analysis to provide an updated incidence rates for the development of low-grade dysplasia (LGD), high-grade dysplasia (HGD), and EAC in a population of patients with BE undergoing endoscopic surveillance. MethodsWe performed a systematic search of EMBASE and Medline from inception to September 2022 to identify studies reporting the incidence rates of LGD, EAC, or HGD/EAC as an outcome in patients with non-dysplastic BE (NDBE), LGD, or HGD. Respective pooled incidence rates were estimated using a meta-analysis. ResultsTwenty-five studies were included in this meta-analysis comprising 2,587 patients with a combined follow-up of 218,351 person-years. For patients with NDBE, pooled incidence rates for progression to LGD, HGD, EAC, and HGD/EAC were 4.29, 0.52, 0.21, and 0.57 per 100 person-years, respectively. For patients with LGD, pooled incidence rates were 3.18 (HGD), 1.16 (EAC), and 5.05 (HGD/EAC) per 100 person-years. For those with HGD, the pooled incidence rate for EAC was 14.16 per 100 person-years. ConclusionsProgression to EAC and HGD/EAC remained low for patients with NDBE. Patients with confirmed LGD (≥2 pathologists) may be more likely to develop EAC, prompting a need to assess current BE surveillance strategies in this group.

Non-erosive gastro-oesophageal reflux disease and incidence of oesophageal adenocarcinoma in three Nordic countries: population based cohort study

ObjectiveTo assess the incidence rate of oesophageal adenocarcinoma among patients with non-erosive gastro-oesophageal reflux disease compared with the general population.DesignPopulation based cohort study.SettingAll patients in hospital and specialised outpatient healthcare...

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

Background and aimsAntireflux 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 (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. MethodsThis multi-national 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 non-operated patients using antireflux medication. The risk of esophageal adenocarcinoma was calculated using multivariable Cox regression, providing hazard ratios (HR) with 95% confidence intervals (CI) adjusted for age, sex, country, calendar year, and comorbidity. ResultsThe 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 to non-operated patients using antireflux medication but rather increased (adjusted HR 1.9, 95% CI 1.1-3.5). Additionally, 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. ConclusionPatients with Barrett’s esophagus who undergo antireflux surgery do not seem to have a lower risk of esophageal adenocarcinoma than those using antireflux medication.

Lactobacillus sp. Facilitate the Repair of DNA Damage Caused by Bile-Induced Reactive Oxygen Species in Experimental Models of Gastroesophageal Reflux Disease.

Gastroesophageal reflux disease (GERD) leads to the accumulation of bile-induced reactive oxygen species and oxidative stress in esophageal tissues, causing inflammation and DNA damage. The progression sequence from healthy esophagus to GERD and eventually cancer is associated with a microbiome shift. Lactobacillus species are commensal organisms known for their probiotic and antioxidant characteristics in the healthy esophagus. This prompted us to investigate how Lactobacilli survive in a bile-rich environment during GERD, and to identify their interaction with the bile-injured esophageal cells. To model human reflux conditions, we exposed three Lactobacillus species (L. acidophilus, L. plantarum, and L. fermentum) to bile. All species were tolerant to bile possibly enabling them to colonize the esophageal epithelium under GERD conditions. Next, we assessed the antioxidant potential of Lactobacilli and role in bile injury repair: we measured bile-induced DNA damage using the ROS marker 8-oxo guanine and COMET assay. Lactobacillus addition after bile injury accelerated repair of bile-induced DNA damage through recruitment of pH2AX/RAD51 and reduced NFκB-associated inflammation in esophageal cells. This study demonstrated anti-genotoxic and anti-inflammatory effects of Lactobacilli, making them of significant interest in the prevention of Barrett's esophagus and esophageal adenocarcinoma in patients with GERD.

Multi-omic features of oesophageal adenocarcinoma in patients treated with preoperative neoadjuvant therapy

Oesophageal adenocarcinoma is a poor prognosis cancer and the molecular features underpinning response to treatment remain unclear. We investigate whole genome, transcriptomic and methylation data from 115 oesophageal adenocarcinoma patients mostly from the DOCTOR phase II clinical trial (Australian New Zealand Clinical Trials Registry-ACTRN12609000665235), with exploratory analysis pre-specified in the study protocol of the trial. We report genomic features associated with poorer overall survival, such as the APOBEC mutational and RS3-like rearrangement signatures. We also show that positron emission tomography non-responders have more sub-clonal genomic copy number alterations. Transcriptomic analysis categorises patients into four immune clusters correlated with survival. The immune suppressed cluster is associated with worse survival, enriched with myeloid-derived cells, and an epithelial-mesenchymal transition signature. The immune hot cluster is associated with better survival, enriched with lymphocytes, myeloid-derived cells, and an immune signature including CCL5, CD8A, and NKG7. The immune clusters highlight patients who may respond to immunotherapy and thus may guide future clinical trials.

Abstract 4233: The anti-genotoxic function of Lactobacillus species in the context of bile-mediated DNA damage and inflammation in experimental models of GERD

Abstract Lactobacillus species are commensal organisms with probiotic characteristics found in the human oral cavity and gastrointestinal tract. It has been shown that gram-positive organisms, including lactobacilli, make up the majority of the microbiome in the healthy human esophagus. The general consensus is that the microbiome shifts from gram-positive to gram-negative bacteria during gastroesophageal reflux disease (GERD). In patients suffering from GERD, the esophageal tissue is injured by the low pH and bile acids present in the refluxate, resulting in Barrett’s esophagus if untreated. Interestingly, it has been reported that there is a proportional increase in gram-positive lactobacilli within the esophagus during the progression from GERD to Barrett’s esophagus, and finally esophageal adenocarcinoma. To investigate how lactobacilli are able to colonize and survive in a bile-rich environment of the esophagus during GERD, we first exposed three Lactobacillus species (L. acidophilus, L. plantarum, and L. fermentum) to cholate/deoxycholate bile salts or ox-bile as a more physiological model for human reflux. All three species exhibited bile resistance, in addition to bile adaptation after pre-exposure to sub-lethal concentrations. When assessed for changes in bacterial cell surface hydrophobicity, an indicator for bacterial adhesion to various surfaces, both bile types led to an increase of hydrophobicity in L. plantarum and L. fermentum, while L. acidophilus remained high. This provides mechanistic insight into how Lactobacillus species' attachment and colonization remain during reflux-related diseases. Next, we assessed the host-microbe interactions between lactobacilli and esophageal cells and the role these probiotic organisms may have in disease prevention. Acidic bile salts can induce inflammation and DNA damage to esophageal tissue through ROS during GERD, yet we found that the presence of lactobacilli co-cultured with bile-treated esophageal epithelial cells aids in the repair of bile-induced DNA damage in addition to NFKB reductions. To further investigate the host-microbe interactions, we supplemented epithelial cells with lactobacilli postbiotic metabolites and assessed cell viability during 48 hours of growth. Our current preliminary data show that postbiotic supplementation increases cell viability, providing insight into why lactobacilli are present within the normal and diseased human esophagus. This study demonstrates how the colonization of the esophagus during GERD with lactobacilli is based on their adaptability and survival due to changes in hydrophobicity thereby sustaining attachment. Furthermore, the anti-genotoxic and anti-inflammatory effects these organisms exhibit make them of significant interest in the prevention of Barrett’s esophagus and esophageal adenocarcinoma in patients with GERD. Citation Format: Joshua Bernard, Divya Joshi, Claudia Andl. The anti-genotoxic function of Lactobacillus species in the context of bile-mediated DNA damage and inflammation in experimental models of GERD. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4233.

Endoscopic eradication therapy for Barrett’s esophagus–related neoplasia: a final 10-year report from the UK National HALO Radiofrequency Ablation Registry

Long-term durability data for effectiveness of radiofrequency ablation (RFA) to prevent esophageal adenocarcinoma in patients with dysplastic Barrett's esophagus (BE) are lacking. We prospectively collected data from 2535 patients with BE (mean length, 5.2 cm; range, 1-20) and neoplasia (20% low-grade dysplasia, 54% high-grade dysplasia, 26% intramucosal carcinoma) who underwent RFA therapy across 28 UK hospitals. We assessed rates of invasive cancer and performed detailed analyses of 1175 patients to assess clearance rates of dysplasia (CR-D) and intestinal metaplasia (CR-IM) within 2 years of starting RFA therapy. We assessed relapses and rates of return to CR-D (CR-D2) and CR-IM (CR-IM2) after further therapy. CR-D and CR-IM were confirmed by an absence of dysplasia and intestinal metaplasia on biopsy samples taken at 2 consecutive endoscopies. Ten years after starting treatment, the Kaplan-Meier (KM) cancer rate was 4.1% with a crude incidence rate of .52 per 100 patient-years. CR-D and CR-IM after 2 years of therapy were 88% and 62.6%, respectively. KM relapse rates were 5.9% from CR-D and 18.7% from CR-IM at 8 years, with most occurring in the first 2 years. Both were successfully retreated with rates of CR-D2 of 63.4% and CR-IM2 of 70.0% 2 years after retreatment. EMR before RFA increased the likelihood of rescue EMR from 17.2% to 41.7% but did not affect the rate of CR-D, whereas rescue EMR after RFA commenced reduced CR-D from 91.4% to 79.7% (χ2P< .001). RFA treatment is effective and durable to prevent esophageal adenocarcinoma. Most treatment relapses occur early and can be successfully retreated.

A Comparative Study between Nissen's Fundoplication with or without Endoscopic Mucosal Resection in the Treatment of Barrett’s Oesophagus: a Meta-Analysis

Abstract Background It is already known that Barrett’s esophagus (BE) is a premalignant condition in which the normal squamous epithelium of the distal esophagus is replaced by columnar epithelium (intestinal metaplasia or gastric metaplasia) due to GERD. Most observers believe that there is a progression from intestinal metaplasia to low-grade dysplasia (LGD) to highgrade dysplasia (HGD) to cancer. The relative risk of developing esophageal adenocarcinoma in patients with BE appears to be 30-fold higher. Conventional therapies include medical treatment (profound acid inhibition), endoscopic treatment (like endoscopic mucosal resection) and surgical treatment (fundoplication). Methodology Types of studies: Published studies about the efficacy of Nissen’s Fundoplication with or without Endoscopic Mucosal Resection in the treatment of Barrett’s Oesophagus (carried out in the period between 2015 – 2020), types of participants Patients with clinically proven Barrett’s Oesophagus diagnosed by endoscopy and biopsy, types of interventions Nissen’s Fundoplication (Open or Laparoscopic) with or without Endoscopic Mucosal Resection, types of outcome measures Outcome of treatment in the form of Complete Remission of Columnar Metaplasia of the oesophageal mucosa or regression in recurrence rate as proved by follow-up endoscopy. Results The strategy of endoscopic therapy for Barrett’s metaplasia, dysplasia and/or intramucosal cancer along with fundoplication results in similar durability and recurrence rates when compared to patients being managed with PPIs following endoscopic therapy. However, fundoplication along with endoscopic therapy is superior to either of them alone in preventing further progression of disease and the development of cancer, particularly in refractory patients. Fundoplication is an important strategy along with endoscopic therapy for Barrett’s to achieve and maintain CR-IM, and to facilitate the eradication of persistent dysplasia. Conclusion Endoscopic mucosal resection after Nissen's Fundoplication is a safe modality, with high rate of success in complete eradication of BE in symptomatic GERD patients, especially those with severe anatomical impairment in distal esophageal segment. As a concurrent procedure, endoscopic procedures may be beneficial in the terms of reducing the early recurrence rates, which seems to be important issue during the management of BE. By doing synchronous endoscopic procedures and fundoplication, one might observe a true anatomy of esophagogastric junction in its entirety and might be able to truly observe the distal extent of columnar esophagus.

S3567 No Barrett's, No Way! A Case of De novo Esophageal Adenocarcinoma

Introduction: Instances of esophageal adenocarcinoma have been increasing at a more drastic rate in the United States and Western Europe in recent years. This calls for more aggressive and comprehensive screening processes for patients with chronic reflux and for those found to have Barrett’s esophagus. Barrett’s esophagus is widely accepted as a precursor to adenocarcinoma of the esophagus, but this case provides a caveat to this rule of thumb. Case Description/Methods: This is a case of a 63-year-old woman who initially presented with severe GERD and was complaining of reflux and regurgitation, as well as nocturnal coughing and wheezing. An endoscopy was conducted revealing LA class 3 esophagitis, a large hiatal hernia, and a distal esophageal inflammatory nodule. The patient was treated aggressively with a combination of a daily PPI and a nightly H2RA. A three-month follow-up endoscopy revealed improvement of her esophagitis, which was downgraded to LA class 1. There was no evidence of Barrett’s esophagus, and the esophageal nodule had healed. Despite this treatment plan the patient was still complaining of regurgitation. An upper GI series revealed a 5 cm hiatal hernia with reflux on water siphon test and valsalva maneuver. Subsequently, a laparoscopic partial fundoplication was performed with complete resolution of all symptoms and successful discontinuance of all acid suppression medications. 2 and ½ years later the patient presented with new onset dysphasia. An upper endoscopy was subsequently performed which revealed a large adenocarcinoma of the distal esophagus and 2 satellite lesions above the adenocarcinoma. Discussion: This case highlights an infrequent presentation of de novo adenocarcinoma with no evidence of Barrett’s esophagus in a conservative time interval. In the chance that the endoscopist may have missed a short segment Barrett’s because of sampling error, the standard of care would have been a 3-year interval surveillance endoscopy. A repeat endoscopy was performed in 2.5 years regardless of no evidence of Barrett’s; the standard of care was not sufficient in this case. This patient exhibited LA class 3-4 distal esophagitis and despite healing, still developed an advanced adenocarcinoma. This may indicate that there is an alternative pathway to esophageal adenocarcinoma in patients with such severe reflux. This case should provide support to potentially screen patients more aggressively who present with severe reflux.Figure 1.: Row 1: initial endoscopy Row 2: second endoscopy Row 3: third endoscopy

Risk of esophageal adenocarcinoma in patients with Barrett's esophagus using proton pump inhibitors: a systematic review with meta-analysis and sequential trial analysis.

BackgroundProton pump inhibitors (PPIs) have been used to treat Barrett’s esophagus (BE), but there seems to be insufficient evidence that PPIs can prevent esophageal adenocarcinoma (EAC) and high grade dysplasia (HGD). This study aimed to evaluate the effects of PPIs in BE patients.MethodsPubMed and EMBASE were systematically searched. Stata13 and trial sequential analysis (TSA) software were used to carry out related statistics. Pooled odds ratio (OR) with 95% confidence intervals (CIs) were calculated.ResultsUsing PPIs to reduce the incidence of EAC and HGD has not been confirmed (OR, 0.61; 95% CI, 0.29–1.26). The pooled results of three cohort studies reported that PPIs use was protective (OR 0.48; 95% CI, 0.33–0.70). But the pooled results of five case-control study indicating PPIs use does not prove this protective effect (OR 0.73; 95% CI, 0.21–2.48). On pooled analysis of 4 US studies 2 Netherlands, protective effect on development of EAC and HGD was noted (OR, 0.59; 95% CI, 0.43–0.80) and (OR, 0.16; 95% CI, 0.03–0.75).ConclusionsAccording to the Meta analysis and TSA of existing studies, the protective effect of PPIs on the progression of BE patients to EAC and/or HGD has not been confirmed. TSA shows that more patients are needed before a clear conclusion can be reached.

Signet Ring Cell Features are Associated with Poor Response to Neoadjuvant Treatment and Dismal Survival in Patients with High-Grade Esophageal Adenocarcinoma.

While the prognosis of patients with locoregional esophageal adenocarcinoma (EAC) has improved in the neoadjuvant treatment (NAT) era, high-grade histology (G3) is still associated with a limited treatment response. We sought to investigate oncologic outcomes in patients after esophagectomy for G3 EAC and to identify predictors of poor survival among these patients. Patients with EAC who underwent resection with curative intent in 2011-2018 were divided by histologic grade (G3, G1/2) and compared for overall survival (OS). Cox regression was performed to analyze the response to NAT and the predictive role of signet ring cell (SRC) features. The cohort included 163 patients, 94 (57.7%) with G3 histology. NAT was administered to 69 (73.4%) patients. Following resection, OS in the G3 EAC group was 30 months (95% confidence interval [CI] 23.9-36.1). On univariate analysis, G3 disease (p=0.050) and SRC features (p=0.019) predicted low OS. Median survival in the G3 EAC group was worse in patients with SRC histology (18 months, 95% CI 8.6-27.4) than those without (30 months, 95% CI 23.8-36.1; p=0.041). No patients with SRC histology were alive at 5 years of follow-up. Among all patients administered NAT, 88.2% of those with SRC showed minimal or no pathologic response and only 27.8% were downstaged. High-grade histology was found in most patients with EAC and predicted poor survival and treatment response. SRC features in patients with G3 disease were associated with lower OS. The benefit of NAT for G3 EAC in patients with SRC histology appears limited.

Adjuvant therapy following neoadjuvant chemotherapy and surgery for oesophageal adenocarcinoma in patients with clear resection margins

Background The role of adjuvant therapy in patients with oesophagogastric adenocarcinoma treated by neoadjuvant chemotherapy (NAC) and surgery is contentious. In UK practice, surgical resection margin status is often used to classify patients into receiving adjuvant treatment. This study aimed to assess any survival benefit of adjuvant therapy in patients with clear resection margins. Methods This was a retrospective collaborative cohort study combining two prospectively collected UK institutional databases of patients with oesophageal adenocarcinoma. Multivariable Cox regression and propensity matched analyses were used to compare overall and recurrence-free survival according to the adjuvant treatment. Results Of 374 patients with clear resection margins, 221 patients (59%) had no adjuvant treatment, 137 patients (37%) had adjuvant chemotherapy and 16 patients (4%) had adjuvant chemoradiotherapy. For patients who had received NAC (290, 76%), when adjuvant chemotherapy was compared to no adjuvant treatment, hazard ratios (HRs) favoured adjuvant chemotherapy but did not reach independent significance (overall survival [OS] HR 0.65 95% confidence interval [CI] 0.40–1.06; p .0.087). Responders to NAC (Mandard 1–3) were seemingly more likely to demonstrate a survival benefit from adjuvant chemotherapy (HR 0.42 95% CI 0.15–1.11; p .1.081). Conclusions Although no independent survival benefit was observed, the point estimates favoured adjuvant treatment, predominantly in patients with chemo-responsive tumours.

Author commentary on Omer Alaber et al.

Omer Alaber et al. High grade dysplasia or esophageal adenocarcinoma in patients with a history of Roux-en-Y gastric bypass surgery: a case series

S0403 Inverse Association Between H. pylori and Esophageal Adenocarcinoma but No Difference in H. pylori Prevalence Between Barrett’s Esophagus and Esophageal Adenocarcinoma—A Systematic Review and Meta-Analysis

INTRODUCTION: The prevalence of H Pylori (HP) is known to be reduced in patients with GERD and Barrett’s Esophagus (BE) compared to population controls without GERD. However, the prevalence of HP does not differ between GERD patients and BE patients, implying that H Pylori does not influence progression of GERD to BE. We have conducted a systematic review and meta-analysis of the prevalence of HP in population controls compared to patients with Esophageal Adenocarcinoma (EAC). Additionally, we have compared HP prevalence in population controls compared to BE patients to EAC patients. METHODS: The MEDLINE, Ovid and Web of Science databases were searched starting in 1988 to 2019. The literature search was conducted using the terms “helicobacter pylori” or “h pylori” or “HP” and “esophageal neoplasms or adenocarcinoma” or “EAC” or “esophageal adenocarcinoma or cancer” or “esophageal tumour.” RESULTS: Literature search revealed 3045 studies, and 284 abstracts were reviewed based on the title. Based on the abstract review 35 full text articles were reviewed and 14 studies were selected for the analysis of HP in controls vs EAC patients. Eleven studies used serology to classify patients as HP positive or negative. Three studies used biopsy to classify patients as HP positive or negative. The 2 cohort studies which were the largest studies in this meta-analysis, included 10158 patients seronegative for HP and 11342 patients seropositive for HP. Patients in these cohort studies were followed for more than 15 years. The pooled odd ratio for EAC in patients with HP positive infection was 0.559 (95% CI 0.466–0.670, P Value 0.00). Thus, HP positivity decreases the risk of EAC by 45%. Additionally, we identified 5 studies that compared prevalence of HP in controls and BE patients and EAC patients. There was no difference in prevalence of HP between patients with BE and EAC. CONCLUSION: We report a lower prevalence of HP infection in EAC patients compared to population controls, but no difference in HP prevalence between patients with BE and EAC. This implies that HP infection seems to protect against the development of BE or EAC, but does not influence the progression of BE to EAC. Widespread antibiotic use may lead to changes in the bacterial microbiome other than eradication of HP. Further studies are needed to delineate non-HP related changes in the bacterial microbiome contributing to the increasing incidence of EAC.Figure 1Figure 2.: Forrest Plot of Pooled Odds ratio of BE & EAC in H. Pylori Positive with GERD as Control.

91 SIMPLE, HIGHLY SENSITIVE CLINICAL PREDICTION SCORES FOR RULING OUT ESOPHAGEAL ADENOCARCINOMA IN PATIENTS WITH BARRETT’S ESOPHAGUS

Abstract Barrett’s Esophagus (BE) is a risk factor for development of Esophageal Adenocarcinoma (EAC). Detection of EAC at an earlier stage is known to improve patient outcomes, but only a very small proportion of patients with BE will progress to EAC. Even in the context of established risk factors, it is difficult to rule out EAC in patients with BE prior to or during endoscopy. Methods We performed a retrospective chart review of all patients with non-dysplastic BE, dysplastic BE and EAC diagnosed at St. Paul’s Hospital from 2012–2016 to investigate patient characteristics that would establish a risk score to discriminate patients with EAC from those without EAC. Results 132 patients were identified. Patients with EAC had higher rate of smoking history (52.4% vs. 20.7%, p = 0.002), higher rate of prior malignancy (33.3% vs. 8.1%, p = 0.001), older mean age (71.0 +/− 8.3 vs. 61.3 +/− 12.2, p = 0.001), greater frequency of carcinoid malignancy (9.5% vs 0.0%, p = 0.024), greater incidence of family history of breast cancer (22.2% vs. 6.2%, p = 0.027) and lung cancer (23.5% vs. 4.1%, p = 0.004) and greater rate of endoscopic mucosal irregularity (85.7% vs. 28.8%, p &amp;lt; 0.001). A clinical risk score to discriminate between patients with EAC from those without EAC had an AUC of 0.90 and NPV of 0.97. Conclusion We have devised clinical risk scores that could be used Risk scores, in combination with established factors such as degree of dysplasia, may help triage patients with BE appropriately with regards to timing of endoscopy. By ruling out EAC and in low risk patients, high risk patients might be monitored more carefully which could lead to earlier detection of EAC and improved patient outcomes.

Molecular biomarker identification for esophageal adenocarcinoma using endoscopic brushing and magnified endoscopy.

Barrett's esophagus (BE) is a predisposing factor for esophageal adenocarcinoma (EAC); however, the precise mechanism underlying this association remains unclear. The identification of biomarkers that are associated with an increased risk of BE progression to EAC would facilitate diagnosis and early treatment. Toward this goal, we aimed to identify biomarkers associated with BE and EAC in patients. In conjunction with high-resolution magnified endoscopy with narrow-band imaging (ME-NBI), we obtained brushing samples from the long-segment BE (LSBE) or short-segment BE (SSBE) of patients with EAC or without EAC (control). To identify candidate biomarker genes, microarray analysis was performed for a training set of 28 American samples. To confirm the microarray results, expression levels of the 16 candidate biomarkers were evaluated by real-time polymerase chain reaction analysis, using samples collected from an additional 53 American patients. In addition, we also performed a functional analysis for these genes using Gene Ontology (GO) enrichment analysis. Among the 16 genes identified as differentially expressed by microarray analysis, the GO analysis indicated matrix metalloproteinase (MMP) family associated with 'collagen metabolic process' and 'multicellular organismal macromolecule metabolic process' as the two top biological processes. Brushing samples of patients with EAC showed up-regulated expression of decay-accelerating factors (DAF and CD55) and topoisomerase type Iiα (TOP2A), and down-regulated expression of the sodium channel epithelial 1 beta subunit (SCNN1B). The up-regulation of CD55 and TOP2A, and the down-regulation of SCNN1B were common to the brushing samples and might serve as molecular biomarkers for identifying EAC in patients with SSBE. University Hospital Medical Information Network (UMIN) (000004004).