Public health importance of the detection of high-grade dysplasia and adenocarcinoma lesions following 2 different protocols: High resolution Virtual chromoendoscopy versus Seattle protocol: CONVERSE study

Public health importance of the detection of high-grade dysplasia and adenocarcinoma lesions following 2 different protocols: High resolution Virtual chromoendoscopy versus Seattle protocol: CONVERSE study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Study protocol Public health importance of the detection of high-grade dysplasia and adenocarcinoma lesions following 2 different protocols: High resolution Virtual chromoendoscopy versus Seattle protocol: CONVERSE study Lucille Queneherve, Jean-Benoit Hardouin, Valery-Pierre Riche, and 24 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5262787/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 08 Jul, 2026 Read the published version in BMC Gastroenterology → Version 1 posted 4 You are reading this latest preprint version Abstract Background: Barrett's esophagus (BE) is a pre-cancerous condition with an increased risk of esophageal adenocarcinoma (EAC). Current surveillance involves white light endoscopy with random biopsies (Seattle Protocol, SP) but has limitations. This study explores high-resolution virtual chromoendoscopy (HRMC) as a potential alternative. Methods: This controlled trial will enroll 110 patients with Barrett's esophagus (BE) across 15 gastroenterology departments in France. Each patient will undergo both HRMC and SP examinations during the same endoscopic procedure. Although the trial is non-randomized, it is important to highlight that the two endoscopists performing either the HRMC or the SP will be blinded to each other’s results. Therefore, each patient will serve as their own control. Biopsy decisions will be based on both methods, with any visible lesions resected. The primary objective is to compare the detection rate of HGD and EAC lesions using HRMC with targeted biopsies versus SP with random biopsies. Secondary objectives include comparing detection rates of LGD lesions, procedure time, missed lesions, and cost-effectiveness. Discussion: If HRMC proves superior to SP for detecting HGD and EAC, it could lead to more accurate, efficient, and cost-effective BE surveillance strategies, improving patient outcomes and resource utilization. Trial Registration: ClinicalTrials.gov NCT05025826 – First Submitted 2021-12-07 Barrett's esophagus Seattle Protocol early cancer detection HRMC Figures Figure 1 Figure 2 Figure 3 Background Esophageal cancer ranks eleventh globally in incidence and seventh in mortality among all cancers [ 1 ]. In 2019, the United States reported 328,030 new cases of digestive diseases, resulting in 165,460 deaths. This included 17,650 new cases of esophageal cancer with 16,080 deaths [ 2 ]. Esophageal cancer comprises two main histological types: adenocarcinoma (EAC) and squamous cell carcinoma (ESCC). EAC primarily affects the lower third of the esophagus and is often preceded by Barrett’s esophagus (BE), a recognized precursor condition. ESCC typically affects the upper two-thirds of the esophagus [ 3 ]. Risk factors for ESCC include smoking and alcohol consumption, while EAC is associated with obesity, Caucasian ethnicity, gastro-esophageal reflux disease (GERD), smoking, and family history [ 4 ]. Historically, ESCC has been predominant, but in developed countries such as the UK, USA, and Australia, there has been a shift towards EAC in recent years [ 5 ]. This shift is attributed to rising GERD incidence due to obesity and poor dietary habits, contributing significantly to BE development. The relative risk of EAC in BE patients is reported as 11.3 [ 6 ]. BE involves metaplastic transformation of esophageal squamous epithelium into columnar epithelium (Fig. 1 ). Disease severity is assessed based on dysplasia presence and degree in biopsy pathology. BE represents a premalignant stage, with annual cancer development risks estimated at 0.33% for non-dysplastic BE, 0.54% for low-grade dysplasia (LGD), and 7% for high-grade dysplasia (HGD) [ 7 ]. The gold standard for BE monitoring is esophagogastroduodenoscopy with random 4-quadrant biopsies (Seattle protocol SP), tailored by BE length which correlates with EAC risk [ 7 – 11 ]. Surveillance aims to detect early EAC, particularly pre-submucosal invasion, which elevates lymph node metastasis risk [ 12 ]. Despite debate on efficacy, systematic biopsies prolong procedures, increase costs, and risk sampling errors, impacting lesion detection and disease management adherence. Financial burdens and resource demands on gastroenterology departments question long-term surveillance efficacy given low disease progression risks. However, large cohort studies (n = 30,000) report earlier EAC detection, improved survival, and reduced cancer-related mortality with surveillance-detected EAC cases [ 13 ]. To address biopsy limitations, advanced imaging like high-resolution endoscopy with magnification and electronic chromoendoscopy (HRMC) emerged, enhancing BE diagnosis. Narrow-band imaging (NBI), using optical filters to enhance microvascular visualization, demonstrates high accuracy in EAC and HGD detection, surpassing white light endoscopy (WLE) in sensitivity, specificity, and biopsy requirements [ 14 – 16 ]. Notably, no trial has compared WLE with SP against HRMC. The CONVERSE study innovates by evaluating HRMC against standard care. Using a crossover design, blinded endoscopists compare HRMC-targeted biopsies with SP 4-quadrant biopsies in the same patient. Lesions detected are immediately resected, potentially altering French and European guidelines to simplify care, reduce biopsies, endoscopy time, sedation needs, and histological interpretation, lowering BE management costs. The French Society of Digestive Endoscopy (SFED) strongly supports this project. The study aims to validate HRMC for BE surveillance, potentially replacing current standards involving numerous biopsies and lengthy procedures. Methods and Design Aims and objective The primary objective of the CONVERSE study is to demonstrate the superiority of high-resolution endoscopy combined with high-resolution magnification chromoendoscopy (HRMC) and targeted biopsies over the current standard of care, which involves white light endoscopy (WLE) with targeted biopsies and systematic biopsies following the SP, for detecting esophageal adenocarcinoma (EAC) and high-grade dysplasia (HGD). The secondary objectives of the study are: To demonstrate the superiority of HRMC with targeted biopsies over WLE with targeted biopsies in detecting HGD and EAC. To demonstrate the superiority of HRMC with targeted biopsies compared to the SP in detecting low-grade dysplasia (LGD). To assess whether HRMC with targeted biopsies reduces the overall procedure time compared to WLE with targeted biopsies combined with SP. To evaluate the potential for missed lesions through an adjudication committee review of procedure videos, divided into two phases: (A) HRMC examination and (B) WLE examination. To demonstrate the superiority of HRMC in guiding the resection of HGD or EAC compared to WLE. To assess the rate of adverse events (AEs) associated with HRMC compared to the standard procedure. To conduct a cost-effectiveness analysis to evaluate the economic impact of HRMC as a surveillance tool in Barrett’s esophagus (BE) management. By achieving these objectives, the study aims to validate HRMC as a more effective, efficient, and potentially cost-saving alternative for the detection and management of dysplasia and early-stage esophageal cancer in BE patients. Study design and setting This study is a multicenter, controlled, and prospective investigation. Although not randomized, endoscopists will remain blinded to each other's assessments during the examinations, ensuring that each patient serves as their own control. This national, multicenter study will involve patients from gastroenterology departments of fifteen French hospitals and clinics, including CHU Nantes, CHU Brest, various APHP sites, CHU Bordeaux, CHU Nice, the Paris – Bercy Clinic, Lyon Civil Hospices, CHU Poitiers, CHU Limoges, CHU Rennes, Sainte Barbe Clinic, CHU Amiens, CHU Nancy, and CHU Besançon. Study population This study will enroll adult patients, aged 18 years or older, both male and female, who are affiliated with the social security system and have been diagnosed with non-dysplastic BE measuring greater than 3 cm in length or any size of dysplastic BE. All eligible participants must have received and signed the informed consent form. Women of childbearing potential must use effective contraception, such as an intrauterine device, oral contraceptives, or implants, for the duration of the study. Several exclusion criteria will be applied. Pregnant or breastfeeding women, as well as patients under legal guardianship, will be excluded. Additionally, patients with a prior history of BE treatment, those with contraindications to sedation or general anesthesia, or those currently taking clopidogrel, anticoagulants, or with coagulopathies will be ineligible. Patients with a general health status that precludes adequate follow-up for BE or those participating in another interventional study will also be excluded. Recruitment is planned over a 36-month period. Inclusion in this protocol will be simple.BE is an asymptomatic epithelial transformation, common in the general population (approximately 1-2%), and currently requires surveillance once histologically confirmed. In France, an estimated 1,500 new cases of esophageal adenocarcinoma (EAC) are diagnosed each year. The dramatic increase in the incidence of EAC over the past decades appears to have been preceded by a similar steep increase in the incidence of BE [17]. Indeed, a 93% increase in the incidence of BE was observed between 1993 and 2005, with a potential confounding bias avoided by counting the number of BE cases per 100 endoscopies [18]. A commonly proposed explanation for the increasing incidence of BE in Western countries is the decreasing prevalence of gastric colonization with Helicobacter pylori [19]. An alternative hypothesis, based on the prevalence of obesity, has been proposed to explain the increasing prevalence of BE and EAC and is gaining popularity [20]. Interventions description Prior to any study-specific procedures, written informed consent will be obtained from all participants. Individuals have the right to withdraw from the study at any time without compromising their ongoing care. Additional research biospecimens (biopsies of lesions detected only by HRMC) will be handled in the same manner as standard biospecimens (other biopsies) by pathology departments. At the conclusion of the trial, all specimens will be stored in pathology departments in accordance with local regulations. As illustrated in the study diagram (Figure 2), the screening visit occurs between Day -60 and Day -1 (D-60 to D-1) prior to endoscopy. On D0 (baseline), an upper gastrointestinal endoscopy is performed under general anesthesia. Each patient serves as their own control. Two endoscopists proceed as follows using the same endoscope: Endoscopist A: Performs HRMC using Blue Light Imaging (BLI) or Narrow Band Imaging (NBI) modalities of the endoscope, meticulously inspecting and documenting all visible lesions with precise location indications (in centimeters from the incisors and clockwise orientation). Annotates on the SFED scheme the biopsies or resections that would have been performed during this procedure. Endoscopist B: Performs the examination using the endoscope's WLE modality and describes all visible lesions, including precise location. At the end of the examination, endoscopists will be unblinded to each other's findings, and either Endoscopist A or B will perform biopsies/resection. Each lesion detected by WLE, HRMC, or both will be transferred to the pathology department in a separate container. For quadrantic biopsies performed according to the SP, each container will hold four quadrant biopsies from the same esophageal level. The procedural schedule is summarized in the following diagram (Figure 3). Recent advancements in endoscopic technology have led to the development of high-resolution endoscopes capable of real-time, detailed visualization of mucosal morphology. These devices, equipped with both WLE and HRMC, are now widely available to endoscopists. Fujifilm and Olympus offer training courses in chromoendoscopy. WLE provides broad-spectrum, high-brightness images of the digestive mucosa, essential for lesion detection. High-resolution endoscopes from Fujifilm® and Olympus® incorporate BLI and NBI, respectively. These electronic chromoendoscopy modalities enhance capillary and mucosal microstructure visualization, improving lesion assessment. All study sites are equipped with high-resolution endoscopes like Olympus Gif 190 or Fuji 760. These devices are standard equipment in these centers and commercially available for the intended use. They will not be labeled as "clinical study" devices. Participating pharmacies will manage device ordering, storage, and distribution. Endoscopic equipment information will be recorded in the e-CRF. On Day 30 (± 7 days), a consultation will be scheduled to review the pathology results with the patient. During this session, the biopsy findings will be communicated, including any detection of precancerous or cancerous cells. Subsequent management will be determined based on these results. Videos showing discrepancies between the endoscopist's observations and the pathologist's findings will be forwarded to the adjudication committee. This committee comprises experts in Barrett's esophagus who are not investigators in the study. The trial schedule is illustrated in Table 1. At the conclusion of the clinical research, the patient will continue to be monitored by their gastroenterologist and will receive the standard care for their condition. Additionally, the sponsor has obtained insurance coverage for its civil liability in accordance with regulations. The treatment duration per patient corresponds to one day for the endoscopy, with a follow-up period of one month. The recruitment period extends to 36 months. Outcomes The primary endpoint of this study is to compare the detection rates of high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) lesions using high-resolution magnification chromoendoscopy (HRMC) with targeted biopsies, which is expected to approach 90%, against the detection rates achieved with white light endoscopy (WLE) using both targeted and random biopsies, anticipated to be around 70%. To ensure consistency in lesion identification, a margin of ±1 cm and ±3 'hours' (equivalent to one-quarter of the circumference in a clock-face orientation) will be applied, indicating that tumors described within these parameters by both endoscopists will be considered identical. The secondary outcomes of this study include the following: First, we will compare the rates of HGD and EAC lesions detected by HRMC with targeted biopsies versus those detected by WLE with targeted biopsies. Second, we will evaluate the rates of low-grade dysplasia (LGD) lesions detected by HRMC with targeted biopsies compared to those identified through the Seattle Protocol (SP). Third, the duration of each procedure—WLE, HRMC, and SP—will be assessed to evaluate efficiency. Additionally, we will analyze the rate of missed lesions (HGD and EAC) as diagnosed by an adjudication committee that reviews procedure videos. We will also determine the rate of resected lesions (HGD and EAC) identified by one endoscopist but overlooked by another. The study will record the number of adverse events (AEs) encountered during the procedures. Finally, a cost-effectiveness analysis will be conducted to compare the two strategies for detecting early EAC and HGD, specifically assessing HRMC against the SP strategy. Statistical analyses A total of 110 patients were required for this study. This sample size was calculated based on a projected Positive Predictive Value (PPV) of 90% for HRMC compared to 70% for WLE, considering a type-I error of 5% and a power of 90% (requiring 67 patients). An additional 50% was added to account for patients with no detected lesions. Due to the possibility of multiple detected lesions per patient, the actual power achieved is expected to exceed the calculated power. Given the nature of the study, where each patient served as their own control, a crossover design was employed. HRMC was always performed first, followed by the Seattle Protocol, with different endoscopists conducting each procedure. To compare the paired proportions of PPVs obtained with HRMC and SP, a McNemar's test was utilized. The PPV for each technique was calculated as the ratio of detected HGD and EAC lesions to all detected lesions. For secondary objectives, given the paired nature of the data, both McNemar's test (for binary variables) and paired Student's t-test (for continuous variables) were employed to compare outcomes between HRM and SP. A health-economic analysis was conducted from a hospital perspective, considering a time horizon starting at the initiation of the study and ending upon the completion of histological results. The comparative effectiveness of the two strategies was assessed based on the number of detected HGD and EAC lesions. Costs were estimated by quantifying biopsy and histology procedures, with resource utilization valued using official NHI fees. Mean costs and their corresponding 95% confidence intervals were reported. A cost-effectiveness plane was used to graphically represent the findings. Interim analyses were not conducted. Similarly, no additional subgroup analyses were performed. Imputation methods were not necessary as data on detection by each technique was available for every lesion identified by HRM and/or SP. Data collection and management Converse’s Scientific Committee was established by Professor Coron and is led by Dr. Queneherve. Its membership encompasses a biostatistician and methodologist, the medico-economist, and the project manager of the Clinical Investigation Center (CIC 1413). The Steering Committee comprises members of the Scientific Committee, augmented by the data management team, the study coordinator responsible for facilitating patient enrollment at additional sites, the sponsor's project manager, and the monitoring Clinical Research Assistant. The sponsor's project manager oversees this committee and produces the "Converse newsletter," which features updates on patient enrollment and protocol amendments. An eCRF will be created for each participant included in CONVERSE. Participants will be identified by a unique code, which will be the sole identifying information included in the eCRF, allowing for retrospective patient linkage. Upon study completion, the CRF database and safety database will undergo reconciliation prior to database lockdown. A similar reconciliation process will occur annually during the Annual Safety Report update. Ethics and disseminations All patient medical data will be disclosed exclusively to the sponsor or their authorized representatives, and where applicable, to authorized health authorities, subject to strict confidentiality. The sponsor and regulatory authorities may request direct access to medical records for verification of study procedures and/or data, as permitted by law and regulation. All trial data will be processed electronically in compliance with CNIL regulations. The CNIL is an independent regulatory authority responsible for enforcing data privacy laws governing the collection, storage, and use of personal information. Aligned with French Law (Jardé n°2012-300), this intervention study poses minimal risks and constraints, mirroring routine care practices rendering a Data and Safety Monitoring Committee unnecessary. While the protocol aims to modify BE monitoring guidelines, emphasizing visualization, the ESGE classifies diagnostic endoscopies, including surveillance with or without biopsy, as low-risk for hemorrhage [21]. Given the minimal risks and constraints, no study-related adverse events are anticipated. Any adverse reactions encountered during patient care willbe reported to the appropriate vigilance system (pharmacovigilance, biovigilance, haemovigilance, medical device vigilance). The amended protocol should be a dated, updated version. If necessary, the informed consent form and patient information sheet should be revised. The CHU Nantes sponsor project manager should notify study sites, and a copy of the revised protocol should be provided to all principal investigators for inclusion in the Investigator Site File. The current protocol version is 4, dated February 24, 2023. Requests for substantial modifications to the protocol should be submitted by the sponsor for approval or notification to the French National Agency for the Safety of Medicines and Health Products (ANSM) and to the Ile-de-France XI –Ethics Committee. A sponsor and/or regulatory authority inspection or audit may occur during this study. Inspectors will examine documents, logistics, records, and any other trial-related materials located at the study site. Trial results will be disseminated through publication in international oncology, medical, and scientific journals, as well as presentations at national and international conferences. The datasets analyzed in the present study along with the statistical code, are accessible upon reasonable request from the corresponding author. The complete study protocol is also available. Discussion Following a review of the protocol, we have modified one inclusion criterion. Initially, patients with non-dysplastic Barrett's esophagus (BE) greater than 3 cm or dysplastic BE of any size were eligible. However, based on preliminary data from the first 22 enrolled patients, we have decided to prioritize patients with dysplastic BE, specifically those with flat lesions. Among the 22 patients initially enrolled, only 5 (23%) exhibited high-grade dysplasia or adenocarcinoma upon examination using at least one of the three techniques (HRMC, WLE, or Seattle quadrantic biopsies). This finding significantly deviates from our initial hypothesis, which anticipated that 67% of patients would present with such lesions. Furthermore, none of the nine patients with non-dysplastic BE greater than 3 cm exhibited high-grade dysplasia or adenocarcinoma. Therefore, we have decided to exclude this patient type from future enrollment. By focusing on patients with flat lesions, which are generally not detectable by white-light endoscopy, we aim to increase the likelihood of identifying dysplastic lesions. To compensate for the exclusion of non-dysplastic BE patients greater than 3 cm, we have requested an increase in the total enrollment number from 100 to 110. This adjustment will ensure that we maintain adequate statistical power for the study. The findings of this study have the potential to significantly improve patient care and public health. By focusing on patients with flat lesions and utilizing HRMC, we anticipate a reduction in the number of biopsies required, thereby decreasing the risk of hemorrhagic complications. Moreover, earlier detection and treatment of lesions could lower the risk of progression to invasive cancer, aligning with the World Health Organization's Global Action Plan for the Prevention and Control of Noncommunicable Diseases (2013–2020). The potential benefits of this study extend beyond individual patient outcomes. By reducing procedure time, HRMC could optimize operating room scheduling for gastroenterologists and endoscopy staff. Additionally, the elimination of random biopsies through HRMC will enable pathologists to focus on targeted biopsies, increasing diagnostic accuracy while reducing costs. Furthermore, the collection of endoscopic video sequences and histological samples of early carcinoma and high-grade dysplasia in Barrett's esophagus will facilitate the development of artificial intelligence projects to improve diagnosis and management of Barrett's esophagus. Trial status This trial is still ongoing; patient inclusion is not yet complete. The updated protocol is at version 4 on February 24 2023. The first patient was enrolled in May 2022. Recruitment by the investigating centers is planned to continue until May 2025. Abbreviations AE ANSM BE BLI CHU CIC CNIL CRF Adverse event Agence Nationale de Santé du Médicament et des produits de santé Barrett’s esophagus Blue Laser Imaging University hospital center Clinical Investigation center Commission Nationale de l’Informatique et des Libertés Case Report Form EAC eCRF ESCC ESGE Esophageal Adenocarcinoma Electronic Case Report Form Esophageal Squamous Cell Carcinoma European Society for Gastrointestinal Endoscopy GERD HGD HRMC ICER LGD NBI PPV SP SFED WLE Gastro-Esophageal Reflux Disease High Grade Dysplasia High Resolution endoscopy combined with Magnification and electronic Chromoendoscopy Incremental cost-effectiveness ratio Low Grade Dysplasia Narrow Band Imaging Positive Predictive Value Seattle Protocol French Society of Digestive Endoscopy White Light Endoscopy Declarations Ethics Approval and Consent to Participate All patients participating in the study are given oral and written information about this trial and sign the informed consent form. This clinical study was submitted to and approved by Ile de France VIII Ethics Committee ( Comité de Protection des Personnes Ile de France XI ) on January 9, 2022. Consent for publication Not applicable - no identifying images or other personal or clinical details of participants are presented here or will be presented in reports of the trial results. Informed consent materials are attached as supplementary materials Availability of data and materials Data collected during the test may be processed electronically, in accordance with the requirements of CNIL (compliance with reference methodology MR001).The investigators will share the entirety of the final trial dataset. Competing interestS There are no financial or competing interests to be declared for the investigators . Funding : This study was supported by a grant from the French National Cancer Institute (INCa) (programme PHRC-K, year 2020 and registered number: PHRC-K20-209). Authors’ contribution EC has the idea of the trial, EC, LQ and AP wrote the study protocol, AP wrote the manuscript. LQ, JBH, YC, VPR, MM, CL, IJA, SB, IA; CR, OP, AJ, GR, AB; DK; CY; MP; TB; IT; MS; JJ; TW; GV; SK; MB; EC assisted with the drafting of the manuscript. MM with the help of CL; CR and OP coordinated the submission of the protocol and the follow-up of (1) the Health Ministry tender and (2) the regulatory authorities and is coordinating the trial. JBH wrote the methodological/statistical analyses in the protocol. VPR and YC wrote the health economic analyses. LG; IA; SB; IJA; CR; OP; GR; AB; DK; CY; MP; TB; IT; MS; JJ; TW; GV; SK; M and EC participated in patient enrolment and follow-up. AJ are assisting with pharmacovigilance for the trial. All authors read and approved the final manuscript. Acknowledgements: This study was supported by a grant from the French Ministry of Health (programme PHRC-K, year 2020 and registered number: PHRC-K20-209 References Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74:229–63. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69:7–34. Domper Arnal MJ, Ferrández Arenas Á, Lanas Arbeloa Á. Esophageal cancer: Risk factors, screening and endoscopic treatment in Western and Eastern countries. World J Gastroenterol. 2015;21:7933–43. Eslick GD. Epidemiology of esophageal cancer. Gastroenterol Clin North Am. 2009;38:17–25, vii. Wong MCS, Hamilton W, Whiteman DC, Jiang JY, Qiao Y, Fung FDH, et al. Global Incidence and mortality of oesophageal cancer and their correlation with socioeconomic indicators temporal patterns and trends in 41 countries. Sci Rep. 2018;8:4522. Hvid-Jensen F, Pedersen L, Drewes AM, Sørensen HT, Funch-Jensen P. Incidence of adenocarcinoma among patients with Barrett’s esophagus. N Engl J Med. 2011;365:1375–83. Shaheen NJ, Falk GW, Iyer PG, Gerson LB, American College of Gastroenterology. ACG Clinical Guideline: Diagnosis and Management of Barrett’s Esophagus. Am J Gastroenterol. 2016;111:30–50; quiz 51. Levine DS, Haggitt RC, Blount PL, Rabinovitch PS, Rusch VW, Reid BJ. An endoscopic biopsy protocol can differentiate high-grade dysplasia from early adenocarcinoma in Barrett’s esophagus. Gastroenterology. 1993;105:40–50. Fitzgerald RC, di Pietro M, Ragunath K, Ang Y, Kang J-Y, Watson P, et al. British Society of Gastroenterology guidelines on the diagnosis and management of Barrett’s oesophagus. Gut. 2014;63:7–42. Weusten B, Bisschops R, Coron E, Dinis-Ribeiro M, Dumonceau J-M, Esteban J-M, et al. Endoscopic management of Barrett’s esophagus: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement. Endoscopy. 2017;49:191–8. Weusten BLAM, Bisschops R, Dinis-Ribeiro M, Pietro M di, Pech O, Spaander MCW, et al. Diagnosis and management of Barrett esophagus: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy. 2023;55:1124–46. Dunbar KB, Spechler SJ. The risk of lymph-node metastases in patients with high-grade dysplasia or intramucosal carcinoma in Barrett’s esophagus: a systematic review. Am J Gastroenterol. 2012;107:850–62; quiz 863. El-Serag HB, Naik AD, Duan Z, Shakhatreh M, Helm A, Pathak A, et al. Surveillance endoscopy is associated with improved outcomes of oesophageal adenocarcinoma detected in patients with Barrett’s oesophagus. Gut. 2016;65:1252–60. Lee MM, Enns R. Narrow band imaging in gastroesophageal reflux disease and Barrett’s esophagus. Can J Gastroenterol. 2009;23:84–7. Jayasekera C, Taylor A, Desmond P, Macrae F, Williams R. Added value of narrow band imaging and confocal laser endomicroscopy in detecting Barrett’s esophagus neoplasia. Endoscopy. 2013;45:484–484. Sharma P, Hawes RH, Bansal A, Gupta N, Curvers W, Rastogi A, et al. Standard endoscopy with random biopsies versus narrow band imaging targeted biopsies in Barrett’s oesophagus: a prospective, international, randomised controlled trial. Gut. 2013;62:15–21. de Jonge PJF, van Blankenstein M, Grady WM, Kuipers EJ. BARRETT’S OESOPHAGUS: EPIDEMIOLOGY, CANCER RISK AND IMPLICATIONS FOR MANAGEMENT. Gut. 2014;63:191–202. Coleman HG, Bhat S, Murray LJ, McManus D, Gavin AT, Johnston BT. Increasing incidence of Barrett’s oesophagus: a population-based study. Eur J Epidemiol. 2011;26:739–45. Rokkas T, Pistiolas D, Sechopoulos P, Robotis I, Margantinis G. Relationship Between Helicobacter pylori Infection and Esophageal Neoplasia: A Meta-analysis. Clinical Gastroenterology and Hepatology. 2007;5:1413-1417.e2. Ryan AM, Duong M, Healy L, Ryan SA, Parekh N, Reynolds JV, et al. Obesity, metabolic syndrome and esophageal adenocarcinoma: epidemiology, etiology and new targets. Cancer Epidemiol. 2011;35:309–19. Veitch AM, Vanbiervliet G, Gershlick AH, Boustiere C, Baglin TP, Smith L-A, et al. Endoscopy in patients on antiplatelet or anticoagulant therapy, including direct oral anticoagulants: British Society of Gastroenterology (BSG) and European Society of Gastrointestinal Endoscopy (ESGE) guidelines. Gut. 2016;65:374–89. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 08 Jul, 2026 Read the published version in BMC Gastroenterology → Version 1 posted Editorial decision: Revision requested 23 Oct, 2024 Editor assigned by journal 15 Oct, 2024 Submission checks completed at journal 15 Oct, 2024 First submitted to journal 14 Oct, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5262787","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Study protocol","associatedPublications":[],"authors":[{"id":369503270,"identity":"30862b87-005c-4493-817d-640afbd472db","order_by":0,"name":"Lucille Queneherve","email":"","orcid":"","institution":"CHU Brest","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Lucille","middleName":"","lastName":"Queneherve","suffix":""},{"id":369503272,"identity":"e5bd17f9-a409-48fd-bdce-0f7b208b49f8","order_by":1,"name":"Jean-Benoit Hardouin","email":"","orcid":"","institution":"Nantes Université, CHU 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CIC1413","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Isabelle","middleName":"","lastName":"ARCHAMBEAUD","suffix":""},{"id":369503278,"identity":"45864d62-23b5-4ca4-add3-e3e0073376d3","order_by":5,"name":"Stephanie Bardot","email":"","orcid":"","institution":"Nantes Université, CHU Nantes and Inserm, Clinical Investigation Centre CIC1413","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Stephanie","middleName":"","lastName":"Bardot","suffix":""},{"id":369503279,"identity":"48ab971c-7f4f-4a0d-b9f5-b098b6126c2b","order_by":6,"name":"Iva Jirka Alebic","email":"","orcid":"","institution":"Nantes Université, CHU Nantes and Inserm, Clinical Investigation Centre CIC1413","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Iva","middleName":"Jirka","lastName":"Alebic","suffix":""},{"id":369503280,"identity":"2857d6b2-9b67-41d1-a334-80db8e8a9665","order_by":7,"name":"Monique Marguerite","email":"","orcid":"","institution":"Nantes Université CHU Nantes","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Monique","middleName":"","lastName":"Marguerite","suffix":""},{"id":369503281,"identity":"8453ff03-19a7-4418-bf80-d8b2214f96da","order_by":8,"name":"Cyrielle Letaillandier","email":"","orcid":"","institution":"Nantes Université CHU Nantes","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Cyrielle","middleName":"","lastName":"Letaillandier","suffix":""},{"id":369503282,"identity":"15bd3516-b9b3-4d2f-826e-6facd6f10724","order_by":9,"name":"Christelle Ratajczak","email":"","orcid":"","institution":"CHU Brest","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Christelle","middleName":"","lastName":"Ratajczak","suffix":""},{"id":369503283,"identity":"6eaeef9c-da1e-4fc3-ad68-d088e2fc7d78","order_by":10,"name":"Océane Pierry","email":"","orcid":"","institution":"CHU Brest","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Océane","middleName":"","lastName":"Pierry","suffix":""},{"id":369503284,"identity":"d5208b4a-0f38-4468-85a0-3013ccd61c87","order_by":11,"name":"Alexandra Jobert","email":"","orcid":"","institution":"Nantes Université CHU Nantes","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Alexandra","middleName":"","lastName":"Jobert","suffix":""},{"id":369503285,"identity":"73c36451-e57a-4f31-bbfc-c1c6c47db6c3","order_by":12,"name":"Gabriel Rahmi","email":"","orcid":"","institution":"Georges Pompidou European Hospital, AP-HP, Paris Descartes University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Gabriel","middleName":"","lastName":"Rahmi","suffix":""},{"id":369503286,"identity":"32cafbb7-ff03-479a-9f11-928e3958b722","order_by":13,"name":"Arthur Berger","email":"","orcid":"","institution":"CHU Bordeaux","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Arthur","middleName":"","lastName":"Berger","suffix":""},{"id":369503287,"identity":"ca80c259-37eb-4428-a4d5-22ed72abfb70","order_by":14,"name":"David Karsenti","email":"","orcid":"","institution":"Paris - Bercy Clinic","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"David","middleName":"","lastName":"Karsenti","suffix":""},{"id":369503288,"identity":"2ed9e349-45b5-4099-9bcd-12a32ac05eca","order_by":15,"name":"Clara Yzet","email":"","orcid":"","institution":"CHU Amiens","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Clara","middleName":"","lastName":"Yzet","suffix":""},{"id":369503289,"identity":"31fab1d2-618b-41b2-bdcf-6823ffd44f3c","order_by":16,"name":"Mathieu Pioche","email":"","orcid":"","institution":"CHU Lyon","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Mathieu","middleName":"","lastName":"Pioche","suffix":""},{"id":369503290,"identity":"81a8831d-3323-4bc9-8d50-00338467db64","order_by":17,"name":"Thierry Barrioz","email":"","orcid":"","institution":"CHU Poitiers","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Thierry","middleName":"","lastName":"Barrioz","suffix":""},{"id":369503291,"identity":"396fe660-50c9-4c5b-b355-dbc1dc1734ed","order_by":18,"name":"Irina Tchoumak","email":"","orcid":"","institution":"Clinic SAINTE-BARBE of the SAINT-VINCENT hospital group","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Irina","middleName":"","lastName":"Tchoumak","suffix":""},{"id":369503292,"identity":"99cc1194-3dbd-4dfe-8453-a52ac19d896b","order_by":19,"name":"Jean-Baptiste Chevaux","email":"","orcid":"","institution":"CHU Nancy, Brabois adults Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jean-Baptiste","middleName":"","lastName":"Chevaux","suffix":""},{"id":369503293,"identity":"19aa0518-940e-49fc-a9ff-656462097980","order_by":20,"name":"Jeremie Jacques","email":"","orcid":"","institution":"CHU Limoges","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jeremie","middleName":"","lastName":"Jacques","suffix":""},{"id":369503294,"identity":"aa94372a-f047-49b0-9d16-c1fcb7415747","order_by":21,"name":"Timothée Wallenhorst","email":"","orcid":"","institution":"CHU Rennes, Pontchaillou Hospital, CIC","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Timothée","middleName":"","lastName":"Wallenhorst","suffix":""},{"id":369503295,"identity":"84898588-c05d-4f03-ad03-936006575aab","order_by":22,"name":"Geoffroy Vanbiervliet","email":"","orcid":"","institution":"Centre Hospitalier Universitaire de Nice","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Geoffroy","middleName":"","lastName":"Vanbiervliet","suffix":""},{"id":369503296,"identity":"e59f696a-cbf4-455b-8ccb-e4ba9f2abe4e","order_by":23,"name":"Stéphane Koch","email":"","orcid":"","institution":"CHU Besançon, CIC","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Stéphane","middleName":"","lastName":"Koch","suffix":""},{"id":369503297,"identity":"78530ad9-53db-45b9-9efb-e82ce1dd59e7","order_by":24,"name":"Maximillien Barret","email":"","orcid":"","institution":"AP-HP Hopital Cochin","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Maximillien","middleName":"","lastName":"Barret","suffix":""},{"id":369503298,"identity":"8af510d7-2c25-416a-8863-03eea37a9752","order_by":25,"name":"Alexandra Poinas","email":"data:image/png;base64,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","orcid":"","institution":"Nantes Université, CHU Nantes and Inserm, Clinical Investigation Centre CIC1413","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Alexandra","middleName":"","lastName":"Poinas","suffix":""},{"id":369503299,"identity":"16859454-cbce-4f1e-a3b5-d561245640a9","order_by":26,"name":"Emmanuel Coron","email":"","orcid":"","institution":"Nantes Université, CHU Nantes and Inserm, Clinical Investigation Centre CIC1413","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Emmanuel","middleName":"","lastName":"Coron","suffix":""}],"badges":[],"createdAt":"2024-10-14 16:53:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5262787/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5262787/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12876-026-05038-3","type":"published","date":"2026-07-08T15:57:42+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":68538998,"identity":"ddd3fde6-b3c8-4aa7-a1a1-43179c342d6a","added_by":"auto","created_at":"2024-11-08 10:34:49","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":238064,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of 2 images of early lesions in Barrett’s esophagus performed using the same endoscope\u003c/p\u003e\n\u003cp\u003e(A) WLE showing no lesion; (B) HRMC (Blue Light Imaging modality) showing a suspicious area for HGD\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-5262787/v1/3408a207db4128a305f81ac6.png"},{"id":68541038,"identity":"b2afcedc-2a25-45dc-9e41-b468f68966e1","added_by":"auto","created_at":"2024-11-08 10:50:49","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":73756,"visible":true,"origin":"","legend":"\u003cp\u003eCONVERSE study design\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-5262787/v1/6fb3455fa667230b626d4b2e.png"},{"id":68540351,"identity":"d0a318ec-8600-41de-8dfd-7d89c14ca4ee","added_by":"auto","created_at":"2024-11-08 10:42:49","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":45509,"visible":true,"origin":"","legend":"\u003cp\u003eThe study’s procedure for the 2 endoscopist\u003c/p\u003e\n\u003cp\u003eVideo 1 will consist in whole examination and lesions description by endoscopist A performing HRMC.\u003c/p\u003e\n\u003cp\u003eVideo 2 will consist in examination and lesions description by endoscopist B under WLE.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-5262787/v1/47ee52d5f297a75250e2a56b.png"},{"id":114598403,"identity":"137b54db-b36c-4dc2-a5a7-0c6dfea4065b","added_by":"auto","created_at":"2026-07-13 16:07:36","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":648750,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5262787/v1/88614bfe-c245-4e7c-882b-85f953eb9915.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Public health importance of the detection of high-grade dysplasia and adenocarcinoma lesions following 2 different protocols: High resolution Virtual chromoendoscopy versus Seattle protocol: CONVERSE study","fulltext":[{"header":"Background","content":"\u003cp\u003eEsophageal cancer ranks eleventh globally in incidence and seventh in mortality among all cancers [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. In 2019, the United States reported 328,030 new cases of digestive diseases, resulting in 165,460 deaths. This included 17,650 new cases of esophageal cancer with 16,080 deaths [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eEsophageal cancer comprises two main histological types: adenocarcinoma (EAC) and squamous cell carcinoma (ESCC). EAC primarily affects the lower third of the esophagus and is often preceded by Barrett\u0026rsquo;s esophagus (BE), a recognized precursor condition. ESCC typically affects the upper two-thirds of the esophagus [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Risk factors for ESCC include smoking and alcohol consumption, while EAC is associated with obesity, Caucasian ethnicity, gastro-esophageal reflux disease (GERD), smoking, and family history [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHistorically, ESCC has been predominant, but in developed countries such as the UK, USA, and Australia, there has been a shift towards EAC in recent years [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. This shift is attributed to rising GERD incidence due to obesity and poor dietary habits, contributing significantly to BE development. The relative risk of EAC in BE patients is reported as 11.3 [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eBE involves metaplastic transformation of esophageal squamous epithelium into columnar epithelium (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Disease severity is assessed based on dysplasia presence and degree in biopsy pathology. BE represents a premalignant stage, with annual cancer development risks estimated at 0.33% for non-dysplastic BE, 0.54% for low-grade dysplasia (LGD), and 7% for high-grade dysplasia (HGD) [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe gold standard for BE monitoring is esophagogastroduodenoscopy with random 4-quadrant biopsies (Seattle protocol SP), tailored by BE length which correlates with EAC risk [\u003cspan additionalcitationids=\"CR8 CR9 CR10\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Surveillance aims to detect early EAC, particularly pre-submucosal invasion, which elevates lymph node metastasis risk [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Despite debate on efficacy, systematic biopsies prolong procedures, increase costs, and risk sampling errors, impacting lesion detection and disease management adherence.\u003c/p\u003e \u003cp\u003eFinancial burdens and resource demands on gastroenterology departments question long-term surveillance efficacy given low disease progression risks. However, large cohort studies (n\u0026thinsp;=\u0026thinsp;30,000) report earlier EAC detection, improved survival, and reduced cancer-related mortality with surveillance-detected EAC cases [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTo address biopsy limitations, advanced imaging like high-resolution endoscopy with magnification and electronic chromoendoscopy (HRMC) emerged, enhancing BE diagnosis. Narrow-band imaging (NBI), using optical filters to enhance microvascular visualization, demonstrates high accuracy in EAC and HGD detection, surpassing white light endoscopy (WLE) in sensitivity, specificity, and biopsy requirements [\u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Notably, no trial has compared WLE with SP against HRMC.\u003c/p\u003e \u003cp\u003eThe CONVERSE study innovates by evaluating HRMC against standard care. Using a crossover design, blinded endoscopists compare HRMC-targeted biopsies with SP 4-quadrant biopsies in the same patient. Lesions detected are immediately resected, potentially altering French and European guidelines to simplify care, reduce biopsies, endoscopy time, sedation needs, and histological interpretation, lowering BE management costs. The French Society of Digestive Endoscopy (SFED) strongly supports this project.\u003c/p\u003e \u003cp\u003eThe study aims to validate HRMC for BE surveillance, potentially replacing current standards involving numerous biopsies and lengthy procedures.\u003c/p\u003e"},{"header":"Methods and Design","content":"\u003cp\u003e\u003cstrong\u003e\u003cu\u003eAims and objective\u0026nbsp;\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe primary objective of the CONVERSE study is to demonstrate the superiority of high-resolution endoscopy combined with high-resolution magnification chromoendoscopy (HRMC) and targeted biopsies over the current standard of care, which involves white light endoscopy (WLE) with targeted biopsies and systematic biopsies following the SP, for detecting esophageal adenocarcinoma (EAC) and high-grade dysplasia (HGD).\u003c/p\u003e\n\u003cp\u003eThe secondary objectives of the study are:\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eTo demonstrate the superiority of HRMC with targeted biopsies over WLE with targeted biopsies in detecting HGD and EAC.\u003c/li\u003e\n \u003cli\u003eTo demonstrate the superiority of HRMC with targeted biopsies compared to the SP in detecting low-grade dysplasia (LGD).\u003c/li\u003e\n \u003cli\u003eTo assess whether HRMC with targeted biopsies reduces the overall procedure time compared to WLE with targeted biopsies combined with SP.\u003c/li\u003e\n \u003cli\u003eTo evaluate the potential for missed lesions through an adjudication committee review of procedure videos, divided into two phases: (A) HRMC examination and (B) WLE examination.\u003c/li\u003e\n \u003cli\u003eTo demonstrate the superiority of HRMC in guiding the resection of HGD or EAC compared to WLE.\u003c/li\u003e\n \u003cli\u003eTo assess the rate of adverse events (AEs) associated with HRMC compared to the standard procedure.\u003c/li\u003e\n \u003cli\u003eTo conduct a cost-effectiveness analysis to evaluate the economic impact of HRMC as a surveillance tool in Barrett\u0026rsquo;s esophagus (BE) management.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eBy achieving these objectives, the study aims to validate HRMC as a more effective, efficient, and potentially cost-saving alternative for the detection and management of dysplasia and early-stage esophageal cancer in BE patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eStudy design and setting\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study is a multicenter, controlled, and prospective investigation. Although not randomized, endoscopists will remain blinded to each other\u0026apos;s assessments during the examinations, ensuring that each patient serves as their own control.\u003c/p\u003e\n\u003cp\u003eThis national, multicenter study will involve patients from gastroenterology departments of fifteen French hospitals and clinics, including CHU Nantes, CHU Brest, various APHP sites, CHU Bordeaux, CHU Nice, the Paris \u0026ndash; Bercy Clinic, Lyon Civil Hospices, CHU Poitiers, CHU Limoges, CHU Rennes, Sainte Barbe Clinic, CHU Amiens, CHU Nancy, and CHU Besan\u0026ccedil;on.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eStudy population\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study will enroll adult patients, aged 18 years or older, both male and female, who are affiliated with the social security system and have been diagnosed with non-dysplastic BE measuring greater than 3 cm in length or any size of dysplastic BE. All eligible participants must have received and signed the informed consent form. Women of childbearing potential must use effective contraception, such as an intrauterine device, oral contraceptives, or implants, for the duration of the study.\u003c/p\u003e\n\u003cp\u003eSeveral exclusion criteria will be applied. Pregnant or breastfeeding women, as well as patients under legal guardianship, will be excluded. Additionally, patients with a prior history of BE treatment, those with contraindications to sedation or general anesthesia, or those currently taking clopidogrel, anticoagulants, or with coagulopathies will be ineligible. Patients with a general health status that precludes adequate follow-up for BE or those participating in another interventional study will also be excluded.\u003c/p\u003e\n\u003cp\u003eRecruitment is planned over a 36-month period. Inclusion in this protocol will be simple.BE is an asymptomatic epithelial transformation, common in the general population (approximately 1-2%), and currently requires surveillance once histologically confirmed. In France, an estimated 1,500 new cases of esophageal adenocarcinoma (EAC) are diagnosed each year.\u003c/p\u003e\n\u003cp\u003eThe dramatic increase in the incidence of EAC over the past decades appears to have been preceded by a similar steep increase in the incidence of BE\u0026nbsp;[17]. Indeed, a 93% increase in the incidence of BE was observed between 1993 and 2005, with a potential confounding bias avoided by counting the number of BE cases per 100 endoscopies\u0026nbsp;[18]. A commonly proposed explanation for the increasing incidence of BE in Western countries is the decreasing prevalence of gastric colonization with Helicobacter pylori\u0026nbsp;[19]. An alternative hypothesis, based on the prevalence of obesity, has been proposed to explain the increasing prevalence of BE and EAC and is gaining popularity\u0026nbsp;[20].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eInterventions description\u0026nbsp;\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePrior to any study-specific procedures, written informed consent will be obtained from all participants. Individuals have the right to withdraw from the study at any time without compromising their ongoing care.\u003c/p\u003e\n\u003cp\u003eAdditional research biospecimens (biopsies of lesions detected only by HRMC) will be handled in the same manner as standard biospecimens (other biopsies) by pathology departments. At the conclusion of the trial, all specimens will be stored in pathology departments in accordance with local regulations.\u003c/p\u003e\n\u003cp\u003eAs illustrated in the study diagram (Figure 2), the screening visit occurs between Day -60 and Day -1 (D-60 to D-1) prior to endoscopy. On D0 (baseline), an upper gastrointestinal endoscopy is performed under general anesthesia. Each patient serves as their own control. Two endoscopists proceed as follows using the same endoscope:\u003c/p\u003e\n\u003cp\u003eEndoscopist A: Performs HRMC using Blue Light Imaging (BLI) or Narrow Band Imaging (NBI) modalities of the endoscope, meticulously inspecting and documenting all visible lesions with precise location indications (in centimeters from the incisors and clockwise orientation). Annotates on the SFED scheme the biopsies or resections that would have been performed during this procedure.\u003c/p\u003e\n\u003cp\u003eEndoscopist B: Performs the examination using the endoscope\u0026apos;s WLE modality and describes all visible lesions, including precise location.\u003c/p\u003e\n\u003cp\u003eAt the end of the examination, endoscopists will be unblinded to each other\u0026apos;s findings, and either Endoscopist A or B will perform biopsies/resection.\u003c/p\u003e\n\u003cp\u003eEach lesion detected by WLE, HRMC, or both will be transferred to the pathology department in a separate container. For quadrantic biopsies performed according to the SP, each container will hold four quadrant biopsies from the same esophageal level. The procedural schedule is summarized in the following diagram (Figure 3).\u003c/p\u003e\n\u003cp\u003eRecent advancements in endoscopic technology have led to the development of high-resolution endoscopes capable of real-time, detailed visualization of mucosal morphology. These devices, equipped with both WLE and HRMC, are now widely available to endoscopists. Fujifilm and Olympus offer training courses in chromoendoscopy. WLE provides broad-spectrum, high-brightness images of the digestive mucosa, essential for lesion detection. High-resolution endoscopes from Fujifilm\u0026reg; and Olympus\u0026reg; incorporate BLI and NBI, respectively. These electronic chromoendoscopy modalities enhance capillary and mucosal microstructure visualization, improving lesion assessment.\u003c/p\u003e\n\u003cp\u003eAll study sites are equipped with high-resolution endoscopes like Olympus Gif 190 or Fuji 760. These devices are standard equipment in these centers and commercially available for the intended use. They will not be labeled as \u0026quot;clinical study\u0026quot; devices. Participating pharmacies will manage device ordering, storage, and distribution. Endoscopic equipment information will be recorded in the e-CRF.\u003c/p\u003e\n\u003cp\u003eOn Day 30 (\u0026plusmn; 7 days), a consultation will be scheduled to review the pathology results with the patient. During this session, the biopsy findings will be communicated, including any detection of precancerous or cancerous cells. Subsequent management will be determined based on these results. Videos showing discrepancies between the endoscopist\u0026apos;s observations and the pathologist\u0026apos;s findings will be forwarded to the adjudication committee. This committee comprises experts in Barrett\u0026apos;s esophagus who are not investigators in the study. The trial schedule is illustrated in Table 1.\u003c/p\u003e\n\u003cp\u003eAt the conclusion of the clinical research, the patient will continue to be monitored by their gastroenterologist and will receive the standard care for their condition. Additionally, the sponsor has obtained insurance coverage for its civil liability in accordance with regulations.\u003c/p\u003e\n\u003cp\u003eThe treatment duration per patient corresponds to one day for the endoscopy, with a follow-up period of one month. The recruitment period extends to 36 months.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eOutcomes\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe primary endpoint of this study is to compare the detection rates of high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) lesions using high-resolution magnification chromoendoscopy (HRMC) with targeted biopsies, which is expected to approach 90%, against the detection rates achieved with white light endoscopy (WLE) using both targeted and random biopsies, anticipated to be around 70%. To ensure consistency in lesion identification, a margin of \u0026plusmn;1 cm and \u0026plusmn;3 \u0026apos;hours\u0026apos; (equivalent to one-quarter of the circumference in a clock-face orientation) will be applied, indicating that tumors described within these parameters by both endoscopists will be considered identical.\u003c/p\u003e\n\u003cp\u003eThe secondary outcomes of this study include the following:\u003c/p\u003e\n\u003cp\u003eFirst, we will compare the rates of HGD and EAC lesions detected by HRMC with targeted biopsies versus those detected by WLE with targeted biopsies. Second, we will evaluate the rates of low-grade dysplasia (LGD) lesions detected by HRMC with targeted biopsies compared to those identified through the Seattle Protocol (SP). Third, the duration of each procedure\u0026mdash;WLE, HRMC, and SP\u0026mdash;will be assessed to evaluate efficiency.\u003c/p\u003e\n\u003cp\u003eAdditionally, we will analyze the rate of missed lesions (HGD and EAC) as diagnosed by an adjudication committee that reviews procedure videos. We will also determine the rate of resected lesions (HGD and EAC) identified by one endoscopist but overlooked by another. The study will record the number of adverse events (AEs) encountered during the procedures. Finally, a cost-effectiveness analysis will be conducted to compare the two strategies for detecting early EAC and HGD, specifically assessing HRMC against the SP strategy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eStatistical analyses\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eA total of 110 patients were required for this study. This sample size was calculated based on a projected Positive Predictive Value (PPV) of 90% for HRMC compared to 70% for WLE, considering a type-I error of 5% and a power of 90% (requiring 67 patients). An additional 50% was added to account for patients with no detected lesions. Due to the possibility of multiple detected lesions per patient, the actual power achieved is expected to exceed the calculated power. Given the nature of the study, where each patient served as their own control, a crossover design was employed. HRMC was always performed first, followed by the Seattle Protocol, with different endoscopists conducting each procedure.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTo compare the paired proportions of PPVs obtained with HRMC and SP, a McNemar\u0026apos;s test was utilized. The PPV for each technique was calculated as the ratio of detected HGD and EAC lesions to all detected lesions. For secondary objectives, given the paired nature of the data, both McNemar\u0026apos;s test (for binary variables) and paired Student\u0026apos;s t-test (for continuous variables) were employed to compare outcomes between HRM and SP.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eA health-economic analysis was conducted from a hospital perspective, considering a time horizon starting at the initiation of the study and ending upon the completion of histological results. The comparative effectiveness of the two strategies was assessed based on the number of detected HGD and EAC lesions. Costs were estimated by quantifying biopsy and histology procedures, with resource utilization valued using official NHI fees. Mean costs and their corresponding 95% confidence intervals were reported. A cost-effectiveness plane was used to graphically represent the findings.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInterim analyses were not conducted. Similarly, no additional subgroup analyses were performed. Imputation methods were not necessary as data on detection by each technique was available for every lesion identified by HRM and/or SP.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eData collection and management\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConverse\u0026rsquo;s Scientific Committee was established by Professor Coron and is led by Dr. Queneherve. Its membership encompasses a biostatistician and methodologist, the medico-economist, and the project manager of the Clinical Investigation Center (CIC 1413). The Steering Committee comprises members of the Scientific Committee, augmented by the data management team, the study coordinator responsible for facilitating patient enrollment at additional sites, the sponsor\u0026apos;s project manager, and the monitoring Clinical Research Assistant. The sponsor\u0026apos;s project manager oversees this committee and produces the \u0026quot;Converse newsletter,\u0026quot; which features updates on patient enrollment and protocol amendments.\u003c/p\u003e\n\u003cp\u003eAn eCRF will be created for each participant included in CONVERSE. Participants will be identified by a unique code, which will be the sole identifying information included in the eCRF, allowing for retrospective patient linkage. Upon study completion, the CRF database and safety database will undergo reconciliation prior to database lockdown. A similar reconciliation process will occur annually during the Annual Safety Report update.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eEthics and disseminations\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll patient medical data will be disclosed exclusively to the sponsor or their authorized representatives, and where applicable, to authorized health authorities, subject to strict confidentiality. The sponsor and regulatory authorities may request direct access to medical records for verification of study procedures and/or data, as permitted by law and regulation. All trial data will be processed electronically in compliance with CNIL regulations. The CNIL is an independent regulatory authority responsible for enforcing data privacy laws governing the collection, storage, and use of personal information.\u003c/p\u003e\n\u003cp\u003eAligned with French Law (Jard\u0026eacute; n\u0026deg;2012-300), this intervention study poses minimal risks and constraints, mirroring routine care practices rendering a Data and Safety Monitoring Committee unnecessary. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWhile the protocol aims to modify BE monitoring guidelines, emphasizing visualization, the ESGE classifies diagnostic endoscopies, including surveillance with or without biopsy, as low-risk for hemorrhage\u0026nbsp;[21]. Given the minimal risks and constraints, no study-related adverse events are anticipated. Any adverse reactions encountered during patient care willbe reported to the appropriate vigilance system (pharmacovigilance, biovigilance, haemovigilance, medical device vigilance).\u003c/p\u003e\n\u003cp\u003eThe amended protocol should be a dated, updated version. If necessary, the informed consent form and patient information sheet should be revised. The CHU Nantes sponsor project manager should notify study sites, and a copy of the revised protocol should be provided to all principal investigators for inclusion in the Investigator Site File. The current protocol version is 4, dated February 24, 2023. Requests for substantial modifications to the protocol should be submitted by the sponsor for approval or notification to the French National Agency for the Safety of Medicines and Health Products (ANSM) and to the Ile-de-France XI \u0026ndash;Ethics Committee.\u003c/p\u003e\n\u003cp\u003eA sponsor and/or regulatory authority inspection or audit may occur during this study. Inspectors will examine documents, logistics, records, and any other trial-related materials located at the study site.\u003c/p\u003e\n\u003cp\u003eTrial results will be disseminated through publication in international oncology, medical, and scientific journals, as well as presentations at national and international conferences. The datasets analyzed in the present study along with the statistical code, are accessible upon reasonable request from the corresponding author. The complete study protocol is also available.\u003cstrong\u003e\u003cu\u003e\u003cbr\u003e\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eFollowing a review of the protocol, we have modified one inclusion criterion. Initially, patients with non-dysplastic Barrett's esophagus (BE) greater than 3 cm or dysplastic BE of any size were eligible. However, based on preliminary data from the first 22 enrolled patients, we have decided to prioritize patients with dysplastic BE, specifically those with flat lesions.\u003c/p\u003e \u003cp\u003eAmong the 22 patients initially enrolled, only 5 (23%) exhibited high-grade dysplasia or adenocarcinoma upon examination using at least one of the three techniques (HRMC, WLE, or Seattle quadrantic biopsies). This finding significantly deviates from our initial hypothesis, which anticipated that 67% of patients would present with such lesions.\u003c/p\u003e \u003cp\u003eFurthermore, none of the nine patients with non-dysplastic BE greater than 3 cm exhibited high-grade dysplasia or adenocarcinoma. Therefore, we have decided to exclude this patient type from future enrollment. By focusing on patients with flat lesions, which are generally not detectable by white-light endoscopy, we aim to increase the likelihood of identifying dysplastic lesions.\u003c/p\u003e \u003cp\u003eTo compensate for the exclusion of non-dysplastic BE patients greater than 3 cm, we have requested an increase in the total enrollment number from 100 to 110. This adjustment will ensure that we maintain adequate statistical power for the study.\u003c/p\u003e \u003cp\u003eThe findings of this study have the potential to significantly improve patient care and public health. By focusing on patients with flat lesions and utilizing HRMC, we anticipate a reduction in the number of biopsies required, thereby decreasing the risk of hemorrhagic complications. Moreover, earlier detection and treatment of lesions could lower the risk of progression to invasive cancer, aligning with the World Health Organization's Global Action Plan for the Prevention and Control of Noncommunicable Diseases (2013\u0026ndash;2020).\u003c/p\u003e \u003cp\u003eThe potential benefits of this study extend beyond individual patient outcomes. By reducing procedure time, HRMC could optimize operating room scheduling for gastroenterologists and endoscopy staff. Additionally, the elimination of random biopsies through HRMC will enable pathologists to focus on targeted biopsies, increasing diagnostic accuracy while reducing costs. Furthermore, the collection of endoscopic video sequences and histological samples of early carcinoma and high-grade dysplasia in Barrett's esophagus will facilitate the development of artificial intelligence projects to improve diagnosis and management of Barrett's esophagus.\u003c/p\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eTrial status\u003c/h2\u003e \u003cp\u003eThis trial is still ongoing; patient inclusion is not yet complete.\u003c/p\u003e \u003cp\u003eThe updated protocol is at version 4 on February 24 2023.\u003c/p\u003e \u003cp\u003eThe first patient was enrolled in May 2022.\u003c/p\u003e \u003cp\u003eRecruitment by the investigating centers is planned to continue until May 2025.\u003c/p\u003e \u003c/div\u003e"},{"header":"Abbreviations","content":"\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eAE\u003c/p\u003e\n \u003cp\u003eANSM\u003c/p\u003e\n \u003cp\u003eBE\u003c/p\u003e\n \u003cp\u003eBLI\u003c/p\u003e\n \u003cp\u003eCHU\u003c/p\u003e\n \u003cp\u003eCIC\u003c/p\u003e\n \u003cp\u003eCNIL\u003c/p\u003e\n \u003cp\u003eCRF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eAdverse event\u003c/p\u003e\n \u003cp\u003eAgence Nationale de Santé du Médicament et des produits de santé\u003c/p\u003e\n \u003cp\u003eBarrett’s esophagus\u003c/p\u003e\n \u003cp\u003eBlue Laser Imaging\u003c/p\u003e\n \u003cp\u003eUniversity hospital center\u003c/p\u003e\n \u003cp\u003eClinical Investigation center\u003c/p\u003e\n \u003cp\u003eCommission Nationale de l’Informatique et des Libertés\u003c/p\u003e\n \u003cp\u003eCase Report Form\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eEAC\u003c/p\u003e\n \u003cp\u003eeCRF\u003c/p\u003e\n \u003cp\u003eESCC\u003c/p\u003e\n \u003cp\u003eESGE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eEsophageal Adenocarcinoma\u003c/p\u003e\n \u003cp\u003eElectronic Case Report Form\u003c/p\u003e\n \u003cp\u003eEsophageal Squamous Cell Carcinoma\u003c/p\u003e\n \u003cp\u003eEuropean Society for Gastrointestinal Endoscopy\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eGERD\u003c/p\u003e\n \u003cp\u003eHGD\u003c/p\u003e\n \u003cp\u003eHRMC\u003c/p\u003e\n \u003cp\u003eICER\u003c/p\u003e\n \u003cp\u003eLGD\u003c/p\u003e\n \u003cp\u003eNBI\u003c/p\u003e\n \u003cp\u003ePPV\u003c/p\u003e\n \u003cp\u003eSP\u003c/p\u003e\n \u003cp\u003eSFED\u003c/p\u003e\n \u003cp\u003eWLE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eGastro-Esophageal Reflux Disease\u003c/p\u003e\n \u003cp\u003eHigh Grade Dysplasia\u003c/p\u003e\n \u003cp\u003eHigh Resolution endoscopy combined with Magnification and electronic Chromoendoscopy\u003c/p\u003e\n \u003cp\u003eIncremental cost-effectiveness ratio\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eLow Grade Dysplasia\u003c/p\u003e\n \u003cp\u003eNarrow Band Imaging\u003c/p\u003e\n \u003cp\u003ePositive Predictive Value\u003c/p\u003e\n \u003cp\u003eSeattle Protocol\u003c/p\u003e\n \u003cp\u003eFrench Society of Digestive Endoscopy\u003c/p\u003e\n \u003cp\u003eWhite Light Endoscopy\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003e\u003cu\u003eEthics Approval and Consent to Participate\u0026nbsp;\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll patients participating in the study are given oral and written information about this trial and sign the informed consent form.\u003c/p\u003e\n\u003cp\u003eThis clinical study was submitted to and approved by Ile de France VIII Ethics Committee (\u003cem\u003eComit\u0026eacute; de Protection des Personnes Ile de France XI\u003c/em\u003e) on January 9, 2022.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eConsent for publication\u0026nbsp;\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable - no identifying images or other personal or clinical details of participants are presented here or will be presented in reports of the trial results. Informed consent materials are attached as supplementary materials\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eAvailability of data and materials\u0026nbsp;\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData collected during the test may be processed electronically, in accordance with the requirements of CNIL (compliance with reference methodology MR001).The investigators will share the entirety of the final trial dataset.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eCompeting interestS\u0026nbsp;\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere are no financial or competing interests to be declared for the investigators .\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eFunding\u003c/u\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cu\u003e:\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by a grant from the French National Cancer Institute (INCa) (programme PHRC-K, year 2020 and registered number: PHRC-K20-209).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eAuthors\u0026rsquo; contribution\u0026nbsp;\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEC has the idea of the trial, EC, LQ and AP wrote the study protocol, AP wrote the manuscript. LQ, JBH, YC, VPR, MM, CL, IJA, SB, IA; CR, OP, AJ, GR, AB; DK; CY; MP; TB; IT; MS; JJ; TW; GV; SK; MB; EC assisted with the drafting of the manuscript. MM with the help of CL; CR and OP coordinated the submission of the protocol and the follow-up of (1) the Health Ministry tender and (2) the regulatory authorities and is coordinating the trial. JBH wrote the methodological/statistical analyses in the protocol. VPR and YC wrote the health economic analyses. LG; IA; SB; IJA; CR; OP; GR; AB; DK; CY; MP; TB; IT; MS; JJ; TW; GV; SK; M and EC participated in patient enrolment and follow-up. AJ are assisting with pharmacovigilance for the trial.\u003c/p\u003e\n\u003cp\u003eAll authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eAcknowledgements:\u0026nbsp;\u003c/u\u003e\u003c/strong\u003eThis study was supported by a grant from the French Ministry of Health (programme PHRC-K, year 2020 and registered number: PHRC-K20-209\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eBray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74:229\u0026ndash;63.\u003c/li\u003e\n \u003cli\u003eSiegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69:7\u0026ndash;34.\u003c/li\u003e\n \u003cli\u003eDomper Arnal MJ, Ferr\u0026aacute;ndez Arenas \u0026Aacute;, Lanas Arbeloa \u0026Aacute;. Esophageal cancer: Risk factors, screening and endoscopic treatment in Western and Eastern countries. World J Gastroenterol. 2015;21:7933\u0026ndash;43.\u003c/li\u003e\n \u003cli\u003eEslick GD. Epidemiology of esophageal cancer. Gastroenterol Clin North Am. 2009;38:17\u0026ndash;25, vii.\u003c/li\u003e\n \u003cli\u003eWong MCS, Hamilton W, Whiteman DC, Jiang JY, Qiao Y, Fung FDH, et al. Global Incidence and mortality of oesophageal cancer and their correlation with socioeconomic indicators temporal patterns and trends in 41 countries. Sci Rep. 2018;8:4522.\u003c/li\u003e\n \u003cli\u003eHvid-Jensen F, Pedersen L, Drewes AM, S\u0026oslash;rensen HT, Funch-Jensen P. Incidence of adenocarcinoma among patients with Barrett\u0026rsquo;s esophagus. N Engl J Med. 2011;365:1375\u0026ndash;83.\u003c/li\u003e\n \u003cli\u003eShaheen NJ, Falk GW, Iyer PG, Gerson LB, American College of Gastroenterology. ACG Clinical Guideline: Diagnosis and Management of Barrett\u0026rsquo;s Esophagus. Am J Gastroenterol. 2016;111:30\u0026ndash;50; quiz 51.\u003c/li\u003e\n \u003cli\u003eLevine DS, Haggitt RC, Blount PL, Rabinovitch PS, Rusch VW, Reid BJ. An endoscopic biopsy protocol can differentiate high-grade dysplasia from early adenocarcinoma in Barrett\u0026rsquo;s esophagus. Gastroenterology. 1993;105:40\u0026ndash;50.\u003c/li\u003e\n \u003cli\u003eFitzgerald RC, di Pietro M, Ragunath K, Ang Y, Kang J-Y, Watson P, et al. British Society of Gastroenterology guidelines on the diagnosis and management of Barrett\u0026rsquo;s oesophagus. Gut. 2014;63:7\u0026ndash;42.\u003c/li\u003e\n \u003cli\u003eWeusten B, Bisschops R, Coron E, Dinis-Ribeiro M, Dumonceau J-M, Esteban J-M, et al. Endoscopic management of Barrett\u0026rsquo;s esophagus: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement. Endoscopy. 2017;49:191\u0026ndash;8.\u003c/li\u003e\n \u003cli\u003eWeusten BLAM, Bisschops R, Dinis-Ribeiro M, Pietro M di, Pech O, Spaander MCW, et al. Diagnosis and management of Barrett esophagus: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy. 2023;55:1124\u0026ndash;46.\u003c/li\u003e\n \u003cli\u003eDunbar KB, Spechler SJ. The risk of lymph-node metastases in patients with high-grade dysplasia or intramucosal carcinoma in Barrett\u0026rsquo;s esophagus: a systematic review. Am J Gastroenterol. 2012;107:850\u0026ndash;62; quiz 863.\u003c/li\u003e\n \u003cli\u003eEl-Serag HB, Naik AD, Duan Z, Shakhatreh M, Helm A, Pathak A, et al. Surveillance endoscopy is associated with improved outcomes of oesophageal adenocarcinoma detected in patients with Barrett\u0026rsquo;s oesophagus. Gut. 2016;65:1252\u0026ndash;60.\u003c/li\u003e\n \u003cli\u003eLee MM, Enns R. Narrow band imaging in gastroesophageal reflux disease and Barrett\u0026rsquo;s esophagus. Can J Gastroenterol. 2009;23:84\u0026ndash;7.\u003c/li\u003e\n \u003cli\u003eJayasekera C, Taylor A, Desmond P, Macrae F, Williams R. Added value of narrow band imaging and confocal laser endomicroscopy in detecting Barrett\u0026rsquo;s esophagus neoplasia. Endoscopy. 2013;45:484\u0026ndash;484.\u003c/li\u003e\n \u003cli\u003eSharma P, Hawes RH, Bansal A, Gupta N, Curvers W, Rastogi A, et al. Standard endoscopy with random biopsies versus narrow band imaging targeted biopsies in Barrett\u0026rsquo;s oesophagus: a prospective, international, randomised controlled trial. Gut. 2013;62:15\u0026ndash;21.\u003c/li\u003e\n \u003cli\u003ede Jonge PJF, van Blankenstein M, Grady WM, Kuipers EJ. BARRETT\u0026rsquo;S OESOPHAGUS: EPIDEMIOLOGY, CANCER RISK AND IMPLICATIONS FOR MANAGEMENT. Gut. 2014;63:191\u0026ndash;202.\u003c/li\u003e\n \u003cli\u003eColeman HG, Bhat S, Murray LJ, McManus D, Gavin AT, Johnston BT. Increasing incidence of Barrett\u0026rsquo;s oesophagus: a population-based study. Eur J Epidemiol. 2011;26:739\u0026ndash;45.\u003c/li\u003e\n \u003cli\u003eRokkas T, Pistiolas D, Sechopoulos P, Robotis I, Margantinis G. Relationship Between Helicobacter pylori Infection and Esophageal Neoplasia: A Meta-analysis. Clinical Gastroenterology and Hepatology. 2007;5:1413-1417.e2.\u003c/li\u003e\n \u003cli\u003eRyan AM, Duong M, Healy L, Ryan SA, Parekh N, Reynolds JV, et al. Obesity, metabolic syndrome and esophageal adenocarcinoma: epidemiology, etiology and new targets. Cancer Epidemiol. 2011;35:309\u0026ndash;19.\u003c/li\u003e\n \u003cli\u003eVeitch AM, Vanbiervliet G, Gershlick AH, Boustiere C, Baglin TP, Smith L-A, et al. Endoscopy in patients on antiplatelet or anticoagulant therapy, including direct oral anticoagulants: British Society of Gastroenterology (BSG) and European Society of Gastrointestinal Endoscopy (ESGE) guidelines. Gut. 2016;65:374\u0026ndash;89.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-gastroenterology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmge","sideBox":"Learn more about [BMC Gastroenterology](http://bmcgastroenterol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmge/default.aspx","title":"BMC Gastroenterology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Barrett's esophagus, Seattle Protocol, early cancer detection, HRMC","lastPublishedDoi":"10.21203/rs.3.rs-5262787/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5262787/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eBarrett's esophagus (BE) is a pre-cancerous condition with an increased risk of esophageal adenocarcinoma (EAC). Current surveillance involves white light endoscopy with random biopsies (Seattle Protocol, SP) but has limitations. This study explores high-resolution virtual chromoendoscopy (HRMC) as a potential alternative.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e This controlled trial will enroll 110 patients with Barrett's esophagus (BE) across 15 gastroenterology departments in France. Each patient will undergo both HRMC and SP examinations during the same endoscopic procedure. Although the trial is non-randomized, it is important to highlight that the two endoscopists performing either the HRMC or the SP will be blinded to each other’s results. Therefore, each patient will serve as their own control. Biopsy decisions will be based on both methods, with any visible lesions resected. The primary objective is to compare the detection rate of HGD and EAC lesions using HRMC with targeted biopsies versus SP with random biopsies. Secondary objectives include comparing detection rates of LGD lesions, procedure time, missed lesions, and cost-effectiveness.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDiscussion:\u003c/strong\u003e If HRMC proves superior to SP for detecting HGD and EAC, it could lead to more accurate, efficient, and cost-effective BE surveillance strategies, improving patient outcomes and resource utilization.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial Registration: \u003c/strong\u003eClinicalTrials.gov NCT05025826 – First Submitted 2021-12-07\u003c/p\u003e","manuscriptTitle":"Public health importance of the detection of high-grade dysplasia and adenocarcinoma lesions following 2 different protocols: High resolution Virtual chromoendoscopy versus Seattle protocol: CONVERSE study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-11-08 10:34:44","doi":"10.21203/rs.3.rs-5262787/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-10-23T11:09:04+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-10-15T23:50:48+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-10-15T23:49:44+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Gastroenterology","date":"2024-10-14T16:40:27+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-gastroenterology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmge","sideBox":"Learn more about [BMC Gastroenterology](http://bmcgastroenterol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmge/default.aspx","title":"BMC Gastroenterology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c79c9563-e67d-4fbb-b3c6-89958b49079e","owner":[],"postedDate":"November 8th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-07-13T16:04:15+00:00","versionOfRecord":{"articleIdentity":"rs-5262787","link":"https://doi.org/10.1186/s12876-026-05038-3","journal":{"identity":"bmc-gastroenterology","isVorOnly":false,"title":"BMC Gastroenterology"},"publishedOn":"2026-07-08 15:57:42","publishedOnDateReadable":"July 8th, 2026"},"versionCreatedAt":"2024-11-08 10:34:44","video":"","vorDoi":"10.1186/s12876-026-05038-3","vorDoiUrl":"https://doi.org/10.1186/s12876-026-05038-3","workflowStages":[]},"version":"v1","identity":"rs-5262787","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5262787","identity":"rs-5262787","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}