Esophageal squamous cell carcinoma (ESCC) remains a significant global health challenge, being the sixth leading cause of cancer mortality with pronounced geographic variability. The incidence rates range from 125 per 100,000 in northern China to 1-1.5 per 100,000 in the United States, driven by environmental and lifestyle factors such as tobacco and alcohol use, dietary habits, and pollution. Major modifiable risk factors include tobacco and alcohol consumption, with a synergistic risk increase when combined. Nonmodifiable risk factors include previous diagnoses of head and neck squamous cell carcinoma (H&N SCC), achalasia, and prior radiotherapy. Prevention strategies must be tailored to specific regional burdens to efficiently allocate medical and financial resources. Gastrointestinal endoscopy is crucial in reducing ESCC burden through early detection and characterization of neoplastic changes, such as high-grade dysplasia. Early diagnosis significantly improves survival rates, while endoscopic resection of noninvasive dysplasia can prevent ESCC onset, reducing treatment burden for advanced disease. Postresection surveillance can detect high-risk metachronous lesions. Despite these benefits, endoscopic prevention faces challenges, including the lack of high-level evidence supporting its efficacy, opportunity costs, the need for specialized training and techniques, and the requirement for advanced technology investments. This Position Statement from the World Endoscopy Organization (WEO) aims to address these challenges, supplying recommendations for the exploitation of endoscopic resources regarding the possible role of screening, quality, and training for the detection, characterization, resection, and surveillance of ESCC.

Background and Aims:Magnetically controlled capsule endoscopy (MCCE) has the potential to allow an operator to move a video capsule endoscope inside the foregut. The primary objective of this pilot study was to demonstrate that MCCE could visualize the major anatomic regions of the stomach in symptomatic patients before an EGD. Secondary objectives were measuring patient satisfaction, patient safety, and comparing MCCE with a follow-up EGD in the detection of any significant gastric lesions. Methods:In this prospective, single-arm, single-center, comparative study, adult patients aged ≥18 years who were referred for an EGD as part of a standard evaluation for symptoms were approached for participation in the study. Participants received MCCE before the EGD. MCCE videos were reviewed by 2 independent physicians and compared with subsequent EGD. Patients were followed for 30 days for safety outcomes and satisfaction. Results:In this study of 40 patients, MCCE detected each of the 6 preidentified major gastric anatomic landmarks with a greater than 95% rate of visualization. Thirty-five patients received a follow-up EGD, and no high-risk lesions were missed with MCCE. Patients preferred MCCE to EGD (80%-13%), and there were no adverse events. Conclusions:In the first pilot study of MCCE in the United States, a high rate of visualization of all regions of the gastric mucosa was achieved. In addition, high satisfaction and no adverse events were recorded. Future studies will focus on higher-risk cohorts to confirm the accuracy of detection of benign, premalignant, and malignant gastric lesions.

BACKGROUND & AIMS:Recommended surveillance intervals after complete eradication of intestinal metaplasia (CE-IM) after endoscopic eradication therapy (EET) are largely not evidence-based. Using recurrence rates in a multicenter international Barrett's esophagus (BE) CE-IM cohort, we aimed to generate optimal intervals for surveillance.METHODS:Patients with dysplastic BE undergoing EET and achieving CE-IM from prospectively maintained databases at 5 tertiary-care centers in the United States and the United Kingdom were included. The cumulative incidence of recurrence was estimated, accounting for the unknown date of actual recurrence that lies between the dates of current and previous endoscopy. This cumulative incidence of recurrence subsequently was used to estimate the proportion of patients with undetected recurrence for various surveillance intervals over 5 years. Intervals were selected that minimized recurrences remaining undetected for more than 6 months. Actual patterns of post-CE-IM follow-up evaluation are described.RESULTS:A total of 498 patients (with baseline low-grade dysplasia, 115 patients; high-grade dysplasia [HGD], 288 patients; and intramucosal adenocarcinoma [IMCa], 95 patients) were included. Any recurrence occurred in 27.1% and dysplastic recurrence occurred in 8.4% over a median of 2.6 years of follow-up evaluation. For pre-ablation HGD/IMCa, intervals of 6, 12, 18, and 24 months, and then annually, resulted in no patients with dysplastic recurrence undetected for more than 6 months, comparable with current guideline recommendations despite a 33% reduction in the number of surveillance endoscopies. For pre-ablation low-grade dysplasia, intervals of 1, 2, and 4 years balanced endoscopic burden and undetected recurrence risk.CONCLUSIONS:Lengthening post-CE-IM surveillance intervals would reduce the endoscopic burden after CE-IM with comparable rates of recurrent HGD/IMCa. Future guidelines should consider reduced surveillance frequency.

Andrew Meltzer: YES financial relationship with a commercial interest;AnX Robotica:Grant/Research Support;Biofire:Grant/Research Support;Medtronic:Grant/Research Support;Vapotherm:Grant/Research Support | Samuel Schueler: NO financial relationship with a commercial interest | David Fleischer: NO financial relationship with a commercial interest | Samuel kallus: NO financial relationship with a commercial interest | Marie Borum: NO financial relationship with a commercial interest | David Cave: YES financial relationship with a commercial interest;Olympus Corp:Grant/Research Support;Anx Robotics:Grant/Research Support;Medtronic:Grant/Research Support;Celgene:Grant/Research Support;Regeneron:Grant/Research Support;Eli Lily:Grant/Research Support;Virgo Surgical Solutions:Advisory Committees or Review Panels;Ironwood:Consulting | Nicole Hall: NO financial relationship with a commercial interest | Priscilla Muhanji: NO financial relationship with a commercial interest | Yan Ma: NO financial relationship with a commercial interest | Arooj Shah: NO financial relationship with a commercial interest

1Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, Arizona, USA; 2Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA. Correspondence: Allon Kahn, MD. E-mail: [email protected].

Background and study aims Dysphagia from esophageal cancer may be palliated with self-expanding metallic stents (SEMS). Controversy exists about the use of dilation before SEMS deployment. Patients and methods We performed a retrospective cohort study of patients who had SEMS placement without fluoroscopy for palliation at Tenwek Hospital in Bomet, Kenya between January 1999 and April 2019. The primary outcome was any serious adverse event (AE) (chest pain, stent migration, perforation, bleeding, or all-cause mortality) within 30 days of the procedure. Various demographic and clinical characteristics, and procedural details, were examined as risk factors. Technical success, defined as correct SEMS placement, and clinical success, defined as dysphagia score improvement without 30-day mortality, were examined. Results A total of 3823 patients underwent SEMS placement, with 2844 (74.4 %) placed in the second decade of the study. Technical and clinical success were achieved in 97.2 % and 95.5 %, respectively, with mean dysphagia scores improving from 3.4 (SD 0.6) to 0.9 (SD 1.3) post-stent placement. AEs occurred in 169 patients (4.4 %). AEs, specifically perforations, were associated with dilation to greater than 36F in the first decade. Perforation rates decreased from the first (4.1 %) to the second decade (0.2 %). Only 30% had complete 30-day follow-up data. Conclusions SEMS placement is a safe, effective method of palliating malignant dysphagia, with low rates of AEs and 30-day mortality and high rates of clinical and technical success. Dilation can facilitate placement of SEMS without fluoroscopy but should not be performed above 36F due to the risk of perforation.

Background and study aims Limited evidence suggests that endoscopy capacity in sub-Saharan Africa is insufficient to meet the levels of gastrointestinal disease. We aimed to quantify the human and material resources for endoscopy services in eastern African countries, and to identify barriers to expanding endoscopy capacity. Patients and methods In partnership with national professional societies, digestive healthcare professionals in participating countries were invited to complete an online survey between August 2018 and August 2020. Results Of 344 digestive healthcare professionals in Ethiopia, Kenya, Malawi, and Zambia, 87 (25.3%) completed the survey, reporting data for 91 healthcare facilities and identifying 20 additional facilities. Most respondents (73.6%) perform endoscopy and 59.8% perform at least one therapeutic modality. Facilities have a median of two functioning gastroscopes and one functioning colonoscope each. Overall endoscopy capacity, adjusted for non-response and additional facilities, includes 0.12 endoscopists, 0.12 gastroscopes, and 0.09 colonoscopes per 100,000 population in the participating countries. Adjusted maximum upper gastrointestinal and lower gastrointestinal endoscopic capacity were 106 and 45 procedures per 100,000 persons per year, respectively. These values are 1% to 10% of those reported from resource-rich countries. Most respondents identified a lack of endoscopic equipment, lack of trained endoscopists and costs as barriers to provision of endoscopy services. Conclusions Endoscopy capacity is severely limited in eastern sub-Saharan Africa, despite a high burden of gastrointestinal disease. Expanding capacity requires investment in additional human and material resources, and technological innovations that improve the cost and sustainability of endoscopic services.

PURPOSE The eastern corridor of Africa is affected by a high burden of esophageal cancer (EC), with > 90% of patients presenting with advanced disease. Self-expanding metal stents (SEMS) have been previously reported as safe and effective for palliation of malignant dysphagia in resource-limited settings; however, access is limited throughout Eastern Africa. METHODS In response to demand for palliative interventions for patients with dysphagia because of EC, the African Esophageal Cancer Consortium (AfrECC) partnered with the Clinton Health Access Initiative to improve access to SEMS in Eastern Africa. We undertook a stepwise implementation approach to (1) identify barriers to SEMS access, (2) conduct a market analysis, (3) select an industry partner, (4) establish regulatory and procurement processes, (5) develop endoscopic training resources, (6) create a medical device registry, and (7) establish principles of accountability. RESULTS Following an evaluation of market demand and potential SEMS manufacturers, Boston Scientific Corporation announced its commitment to launch an access program to provide esophageal SEMS to patients in Tanzania, Kenya, Malawi, and Zambia at a subsidized price. Parallel regulatory and procurement processes were established in each participating country. Endoscopy training courses were designed and conducted, using the Training-of-Trainers model. A device registry was created to centralize data for quality control and to monitor channels of SEMS distribution. Principles of accountability were developed to guide the sustainability of this endeavor. CONCLUSION The AfrECC Stent Access Initiative is an example of a multisector partnership formed to provide an innovative solution to align regional needs with a supply chain for a high-priority medical device.

Following complete eradication of intestinal metaplasia (CE-IM) with endoscopic therapy for dysplastic Barrett's esophagus (BE), recurrence is well described. Current post-CE-IM surveillance intervals are not evidence based. Recent modeling studies have suggested lengthening of surveillance intervals. We aimed to examine alternative post-treatment surveillance intervals using recurrence data from a large international multicenter cohort.

BACKGROUND:Volumetric laser endomicroscopy (VLE) allows for near-microscopic imaging of the superficial esophageal wall and may improve detection of early neoplasia in Barrett's esophagus (BE). Interpretation of a 6-cm long, circumferential VLE "full scan" may however be challenging for endoscopists. We aimed to evaluate the accuracy of VLE experts in correctly diagnosing VLE full scans of early neoplasia and non-dysplastic BE (NDBE). METHODS:29 VLE full scan videos (15 neoplastic and 14 NDBE) were randomly evaluated by 12 VLE experts using a web-based module. Experts were blinded to the endoscopic BE images and histology. The 15 neoplastic cases contained a subtle endoscopically visible lesion, which on endoscopic resection showed high grade dysplasia or cancer. NDBE cases had no visible lesions and an absence of dysplasia in all biopsies. VLE videos were first scored as "neoplastic" or "NDBE." If neoplastic, assessors located the area most suspicious for neoplasia. Primary outcome was the performance of VLE experts in differentiating between non-dysplastic and neoplastic full scan videos, calculated by accuracy, sensitivity, and specificity. Secondary outcomes included correct location of neoplasia, interobserver agreement, and level of confidence. RESULTS:VLE experts correctly labelled 73 % (95 % confidence interval [CI] 67 % - 79 %) of neoplastic VLE videos. In 54 % (range 27 % - 66 %) both neoplastic diagnosis and lesion location were correct. NDBE videos were consistent with endoscopic biopsies in 52 % (95 %CI 46 % - 57 %). Interobserver agreement was fair (kappa 0.28). High level of confidence was associated with a higher rate of correct neoplastic diagnosis (81 %) and lesion location (73 %). CONCLUSIONS:Identification of subtle neoplastic lesions in VLE full scans by experts was disappointing. Future studies should focus on improving methodologies for reviewing full scans, development of refined VLE criteria for neoplasia, and computer-aided diagnosis of VLE scans.

Background and Aims: Radiofrequency ablation (RFA) is the preferred ablativemodality for treating dysplastic Barrett's esophagus. The recently introduced self-sizing circumferential ablation catheter eliminates the need for a sizing balloon. Although it enhances efficiency, outcomes have not been compared with the previousmanual-sizing catheter. We evaluated the comparative safety and efficacy of these 2 ablation systems in a large, multicenter cohort. Methods: Patients undergoing RFA at 3 tertiary care centers from 2005 to 2018 were included. Circumferential RFA was performed in a standard fashion, followed by focal RFA as needed. Outcomes were compared between the self-sizing and manual-sizing groups. The primary outcome was the rate of adverse events, including strictures, perforation, and bleeding. Secondary outcomes were procedure time and treatment efficacy, as assessed by rates and time to complete eradication of dysplasia (CE-D) and intestinal metaplasia (CE-IM). Results: Three hundred eighteen patients were included, 90 (28.3%) treated with the self-sizing catheter and 228 (71.7%) with the manual-sizing catheter. Twenty-one patients (6.6%) developed strictures (8 [8.9%] in the selfsizing group and 13 [5.7%] in the manual-sizing group, P = .32). Of the self-sizing strictures, 75% occurred at the 12J dose before widespread adoption of the current 10J treatment standard. One patient developed bleeding, and no perforations were encountered. Procedure time was significantly shorter in the self-sizing group. No significant differences were observed in rates of and time to CE-D and CE-IM. Conclusions: These findings suggest that both systems are comparable in safety and efficacy. The use of the selfsizing system may enhance the efficiency of RFA for treating dysplastic Barrett's esophagus.

There is a high incidence of esophageal squamous cell cancer (ESCC) in East Africa, where most patients present with advanced disease and severe dysphagia. Placement of self-expanding metal stents (SEMS) provides safe and effective palliation in resource-limited settings, but access to SEMS in Africa has been hampered by cost and lack of trained endoscopists. The aim of this report is to describe a regional initiative to increase SEMS access, launched by the African Esophageal Cancer Consortium (AfrECC). AfrECC has 1) identified an industry partner (Boston Scientific Corporation) committed to supplying affordable, high quality SEMS for placement by trained endoscopists, 2) worked to develop country specific and multi-national regulatory strategies for importation of SEMS, 3) created a modular training program for East African endoscopists with standardized assessments of competency to a) deploy SEMS and b) train other endoscopists in SEMS placement, and 4) established a device registry including data on patient outcomes. To date, 30 endoscopists at 7 hospitals in Kenya, Tanzania, Zambia and Malawi have been trained in deployment of the Ultraflex SEMS by 3 expert trainers. Six week-long training sessions have been held over 18 months. 252 SEMS have been placed in symptomatic patients during these sessions, using a non-fluoroscopic technique, without clinically significant adverse events. All 30 endoscopists achieved competence to place stents, and 11 endoscopists achieved competence as SEMS trainers. Teams of trainers in each country have now begun training additional endoscopists. SEMS are an important element of ESCC care in East Africa. A regional initiative to improve SEMS access can be effectively implemented, and requires partnership with industry and government stakeholders, as well as a modular training curriculum, standardized assessments, and pre-defined criteria for both stent placement competency and trainer competency. Patient outcomes data collected as part of a device registry may ultimately provide further validation of this initiative.

Resection of early EAC (stage T1), either by surgical or endoscopic methods, is widely accepted. Long term outcome data in patients with T1 esophageal adenocarcinoma (EAC) (beyond the first five years of remission) are lacking and critical to decision making in those with longer life expectancy. We aimed to assess the long term outcomes of patients treated for T1EAC at three large academic institutions, focusing primarily on EAC recurrence rates and survival beyond the first five years.

Radiofrequency ablation (RFA) is the current standard of care for the ablation of BE related dysplasia and can be performed with both circumferential and focal devices. Recently a self sizing circumferential © RFA catheter (Halo 360 Express) eliminating the need for sizing, has been introduced with some concerns regarding dosimetry and safety, particularly in terms of stricture rates. We aimed to compare the safety (as primary outcome) and efficacy (time to and proportion of complete remission of dysplasia (CR-D) and complete remission of intestinal metaplasia(CR-IM) as secondary outcomes) of the Halo 360 Express catheter with that of the older Halo 360 catheter in a multicenter cohort study.

Esophageal cancer is the eighth most common cancer worldwide and represents the sixth leading cause of global cancer mortality.1Abnet C.C. Arnold M. Wei W.Q. Epidemiology of esophageal squamous cell carcinoma.Gastroenterology. 2018; 154: 360-373Abstract Full Text Full Text PDF PubMed Scopus (697) Google Scholar Although esophageal adenocarcinoma (EAC) now accounts for the majority of esophageal cancer diagnosed in the United States, esophageal squamous cell carcinoma (ESCC) remains far more prevalent worldwide. The International Agency for Research on Cancer estimates that 88% of esophageal cancer cases in 2012 were ESCC, with only 12% representing EAC. ESCC exhibits a striking regional variation in incidence, both globally and within a single nation. The highest incidence regions are concentrated in 2 bands, 1 extending from northern Iran through central Asia to North Central China and the other in East Africa. Most patients with ESCC present with advanced stage disease, which is incurable. In the United States, 38% present at stage 4 disease, and the 5-year survival is 12% for all comers.2Siegel R.L. Miller K.D. Jemal A. Cancer statistics, 2016.CA Cancer J Clin. 2016; 66: 7-30Crossref PubMed Scopus (21977) Google Scholar In developing nations, the prognosis is far worse, with 5-year survival rates consistently below 5% and as low as 0.8% in high-risk regions.3Aghcheli K. Marjani H.A. Nasrollahzadeh D. et al.Prognostic factors for esophageal squamous cell carcinoma--a population-based study in Golestan Province, Iran, a high incidence area.PLoS One. 2011; 6: e22152Crossref PubMed Scopus (50) Google Scholar Studies have established squamous dysplasia and SCC in situ as precursor lesions to ESCC and have demonstrated that endoscopic treatment can prevent disease progression.4Subramanian C.R. Triadafilopoulos G. Diagnosis and therapy of esophageal squamous cell dysplasia and early esophageal squamous cell cancer.Gastroenterol Rep. 2017; 5: 247-257Google Scholar In the United States, population-based screening for ESCC is not recommended5Wang K.K. Wongkeesong M. Buttar N.S. American Gastroenterological Association technical review on the role of the gastroenterologist in the management of esophageal carcinoma.Gastroenterology. 2005; 128: 1471-1505Abstract Full Text Full Text PDF PubMed Scopus (70) Google Scholar because of the relatively low disease incidence and a resulting lack of evidence for efficacy and cost effectiveness. By contrast, China has instituted an endoscopic screening program with Lugol chromoendoscopy for all adults aged 40 to 69 residing in high-risk regions, resulting in decreases of 30% in cumulative incidence and 33% in cumulative ESCC-related mortality.6Wei W.Q. Chen Z.F. He Y.T. et al.Long-term follow-up of a community assignment, one-time endoscopic screening study of esophageal cancer in China.J Clin Oncol. 2015; 33: 1951-1957Crossref PubMed Scopus (198) Google Scholar Given the marked variation in incidence among regions and communities and the success of targeted screening programs, accurate risk stratification is critical to the future of identifying and treating ESCC. The study by Wang et al7Wang Q.-L. Lagergren J. Xie S.-H. Prediction of individuals at high absolute risk of esophageal squamous cell carcinoma.Gastrointest Endosc. 2019; 89: 726-732Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar was conducted with the aim of synthesizing several existing risk factors into a cohesive and readily applicable risk assessment model to identify the absolute 5-year risk for the development of ESCC. This was a nested case-control study within the context of a nationwide population-based study of esophageal adenocarcinoma whose results were previously published.8Lagergren J. Bergstrom R. Lindgren A. et al.Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma.N Engl J Med. 1999; 340: 825-831Crossref PubMed Scopus (2585) Google Scholar The authors identified one half of all patients with cases of ESCC among the Swedish population during the study period of 1995 to 1997 and compared them with a group of control individuals matched by age and sex to the prior EAC cohort to generate multivariable logistic regression models. Both simple (4-variable: age, sex, tobacco, alcohol) and comprehensive (6-variable: added formal education and duration of living with partner) prediction models were constructed, and odds ratios generated by the models were combined with ESCC incidence data and population-based mortality data to estimate individual 5-year ESCC incidence risk. The authors found that both simple and comprehensive models exhibited reasonably good accuracy in predicting ESCC risk, with leave-one-out cross-validated area under the curve (AUC) of 0.75 (95% confidence interval, 0.75-0.78) and 0.78 (95% confidence interval, 0.71-0.79), respectively. They used their model to construct a calculator for estimating an individual’s risk based on their personal risk factor profile. The model was also used to estimate the number needed to screen to detect a single case of ESCC for each combination of risk factors. The authors should be commended for the use of the leave-one-out cross-validation strategy to estimate error variance and model performance while partially controlling for model overfitting. The data collection methods were similarly rigorous because all cases of ESCC in the entire national health system were identified and systematically processed according to a standardized protocol, including face-to-face interviews. Furthermore, this is the first study to provide individualized risk estimates to guide clinical decision making. However, as discussed by the authors, the models will require external validation to evaluate clinical utility outside of the limited population studied. Although the novelty of the current study lies in the identification of individual ESCC risk for a Western population, others have attempted to combine known ESCC risk factors into risk stratification models in areas of higher prevalence. These prior studies were nicely highlighted by Wang et al7Wang Q.-L. Lagergren J. Xie S.-H. Prediction of individuals at high absolute risk of esophageal squamous cell carcinoma.Gastrointest Endosc. 2019; 89: 726-732Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar in their discussion of the present study, but the comparisons are worth revisiting. The authors of this study emphasize the enhanced AUC of both their simple and full predictive models when compared with prior studies. Etemadi et al9Etemadi A. Abnet C.C. Golozar A. et al.Modeling the risk of esophageal squamous cell carcinoma and squamous dysplasia in a high risk area in Iran.Arch Iran Med. 2012; 15: 18-21PubMed Google Scholar conducted a case-control study in a high-risk Iranian province and examined data from 300 ESCC case patients and 571 age and sex-matched control individuals. The model developed by the Iranian group demonstrated a cross-validated AUC of 0.77, which is comparable to the level of 0.78 seen here and superior to 0.75 seen in the simpler model in the present study. In contrast to the present study, other models have ordinarily included or focused on the identification of squamous dysplasia, not ESCC, because of the enhanced opportunity for early intervention before the development of carcinoma. Wei et al10Wei W.Q. Abnet C.C. Lu N. et al.Risk factors for oesophageal squamous dysplasia in adult inhabitants of a high risk region of China.Gut. 2005; 54: 759-763Crossref PubMed Scopus (92) Google Scholar screened 720 individuals in a high-prevalence Chinese province, of whom 32% demonstrated squamous dysplasia. The AUC of their model to predict squamous dysplasia was clearly suboptimal at 0.58. However, a subsequent study in the same Chinese region analyzed data from 15,073 individuals and built multivariable logistic regression models to stratify the risk of moderate and severe squamous dysplasia.11Liu M. Liu Z. Cai H. et al.A model to identify individuals at high risk for esophageal squamous cell carcinoma and precancerous lesions in regions of high prevalence in China.Clin Gastroenterol Hepatol. 2017; 15: 1538-1546 e7Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar They identified higher age as being predictive of squamous dysplasia and therefore created age-stratified prediction models. This allowed for the identification of predictive variables within each age group (ie, ≤60 or >60 years old). As an example, the use of coal or wood as a main source of cooking fuel and rapid ingestion of food were unique predictors of squamous dysplasia in the ≤60 group, whereas pesticide exposure, smoking, and family history of ESCC were predictive in the >60 group. The performance characteristics were reasonable, with AUC of 0.795 and 0.681, respectively. Importantly, the authors estimate that applying this model, in contrast to universal screening, would maintain 100% sensitivity for squamous dysplasia while leading to 27% and 9% reductions in the number of endoscopies needed in these groups. Furthermore, this study achieved a cross-validated AUC of 0.76 in the ≤60-year-old group for severe squamous dysplasia or above, comparable with Wang and a more valuable clinical endpoint. The study by Wang et al7Wang Q.-L. Lagergren J. Xie S.-H. Prediction of individuals at high absolute risk of esophageal squamous cell carcinoma.Gastrointest Endosc. 2019; 89: 726-732Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar has important limitations. The models do not contain any novel risk factors beyond those used in existing studies. Thus, these findings may reflect that existing risk factors, such as age, sex, tobacco smoking, and alcohol overconsumption are better predictors of ESCC incidence in a Western population than in higher-prevalence regions in the East. Perhaps most importantly, the study’s principal innovation (estimating ESCC risk in a Western population) was necessarily constructed and validated on a population at low baseline risk for the development of ESCC. In a 3-year study in a country of 10 million people, only 456 cases were diagnosed. The incidence of ESCC in Sweden is among the lowest in the world and has been steadily declining since 1985.12Wang Q.L. Xie S.H. Wahlin K. et al.Global time trends in the incidence of esophageal squamous cell carcinoma.Clin Epidemiol. 2018; 10: 717-728Crossref PubMed Scopus (50) Google Scholar Examining the provided supplementary figures, even for the highest-risk patient of advanced age with a history of extensive smoking and alcohol consumption, the number needed to screen was 761, whereas for younger patients with even modest histories of smoking and alcohol use, the estimated number needed to screen was often above 3000. Although such data are not provided, with such a low national incidence, even a tailored screening program may not prove cost effective. The limitation of current screening methods is closely tied to the resource-intensive nature of endoscopic screening, which is poorly applicable to many endemic regions of high ESCC prevalence. As a result, a variety of screening methods have been developed and tested in an effort to provide safe, effective, nonendoscopic screening to these high-risk populations. They have included several nonendoscopic tissue sampling devices, such as balloons and sponges, which have exhibited reasonable specificity but limited sensitivity. More recently, additional biomarkers, such as circulating mRNA, methylated DNA, and volatile organic compounds, have demonstrated promising detection accuracy. The full details of these efforts are beyond the scope of this commentary. It is our strong belief that the most important step in reducing the mortality from ESCC is the development and perfection of nonendoscopic screening methods as described in the recent review article by Codipilly et al.13Codipilly D.C. Qin Y. Dawsey S.M. et al.Screening for esophageal squamous cell carcinoma: recent advances.Gastrointest Endosc. 2018; 88: 413-426Abstract Full Text Full Text PDF PubMed Scopus (106) Google Scholar The scarcity of resources in precisely those developing nations where ESCC incidence is highest results in devastating patient outcomes. Esophageal cancer not only shortens the patient's life but also saps the quality of the remaining months of life by preventing the patient from sharing meals and other social situations with friends and relatives, because they cannot swallow their own secretions and are embarrassed by this. Although significant strides have been made in understanding the risk factors, regional incidence variability, and even effective screening interventions in other high-risk regions, such as Iran and northern China, Eastern Africa remains a region of high disease burden and relatively little research or coordinated intervention. As a result, the International Agency for Research on Cancer, the United States National Cancer Institute, the American Cancer Society, the Clinton Health Initiative, academic medical centers (Mayo Clinic, University of California San Francisco, Tenwek Hospital in Kenya, Muhimbili National Hospital in Tanzania, and others), and industry (Boston Scientific) have formed the African Esophageal Cancer Consortium to conduct epidemiologic, clinical, and molecular research and to lead efforts in strengthening clinical collaborations, research infrastructure, training, and capacity building in sub-Saharan Africa.14Van Loon K. Mwachiro M.M. Abnet C.C. et al.The African Esophageal Cancer Consortium: a call to action.J Glob Oncol. 2018; : 1-9Google Scholar This study reminds us that we are at a key inflection point in the global investigation of ESCC. Should we follow strategies that are used in developed countries and focus our efforts on increasingly refined stratification tools to identify a small population that may benefit from enhanced screening and intervention? Or should we look to new strategies in high-incidence developing countries where they are expanding these methodologies, strengthened by the inclusion of emerging regional risk factors (such as polycyclic aromatic hydrocarbon exposure, soil selenium content, and high beverage temperature15Kamangar F. Chow W.H. Abnet C.C. et al.Environmental causes of esophageal cancer.Gastroenterol Clin North Am. 2009; 38: 27-57Abstract Full Text Full Text PDF PubMed Scopus (296) Google Scholar)? The most important next step will be using nonendoscopic screening methods for the precursors of ESCC in these regional high-risk populations. Out with the old. In with the new. The author disclosed no financial relationships relevant to this publication. Prediction of individuals at high absolute risk of esophageal squamous cell carcinomaGastrointestinal EndoscopyVol. 89Issue 4PreviewThis study aimed to develop a prediction model for identifying individuals at high absolute risk of esophageal squamous cell carcinoma (ESCC) for endoscopic screening at a curable stage based on readily identifiable risk factors. Full-Text PDF

Goals: To investigate factors predictive of progression from nondysplastic Barrett esophagus (NDBE) or low-grade dysplasia (LGD) to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) using a large, prospective cohort of patients, wherein all esophageal biopsies undergo expert gastrointestinal pathologist review. Background: Efficacy and cost-effectiveness of endoscopic surveillance to detect incident EAC in the setting of Barrett esophagus (BE), particularly in NDBE patients, is questioned. Previous studies have reported factors predictive of progression to EAC to guide surveillance intervals, but their strength is limited by small sample size and absence of expert gastrointestinal pathologist involvement in esophageal biopsy review. Study: NDBE and LGD subjects were identified from a prospective registry in a tertiary care center. “Progressors” were BE subjects who developed HGD/EAC>12 months after the initial NDBE or LGD diagnosis. Cox proportional hazards model were used to identify predictors of progression. Results: In total, 318 with NDBE and 301 with BE-LGD (mean age, 62.6 y, 85% male) were included. The mean follow-up was 5.3 years. The 7 NDBE and 21 LGD subjects progressed to HGD/EAC. BE length [hazards ratio (HR), 1.16; 95% confidence interval (CI), 1.03-1.29], presence of nodularity (HR, 4.98; 95% CI, 1.80-11.7), and baseline LGD (HR, 2.57; 95% CI, 1.13-6.57) were significant predictors of progression on multivariate analysis. Conclusions: In this well-defined cohort of NDBE and BE-LGD subjects, BE length, presence of LGD, and nodularity were independent predictors of progression to HGD/EAC. These factors may aid in identifying high-risk patients who may benefit from closer endoscopic surveillance/therapy.

Background and Aims: Radiofrequency ablation (RFA) is an accepted treatment for flat Barrett's neoplasia. Less is known about RFA for esophageal squamous cell neoplasia (ESCN). Our group has reported several prospective studies of RFA for ESCN in China with promising results through 12 months of follow-up. In this cohort study we aimed to evaluate longer term outcomes after RFA for ESCN. Methods: Patients with flat unstained lesions (USLs) on Lugol's endoscopy containing moderate-/high-grade intraepithelial neoplasia (MGIN/HGIN) or mucosal cancer were treated with RFA every 3 months until complete remission (CR; no MGIN or a worse histologic grade). Patients with CR at 12 months (CR12) were included for follow-up and underwent annual Lugol's endoscopy with biopsy sampling and re-RFA for flat USLs. The clinical course of patients with persistent ESCN at 12 months (treatment failures) is also reported. Results: Among the 78 patients in CR12, 67 (86%) had sustained CR during a median of 48 months (interquartile range, 48-48) of follow-up and 5 endoscopies (interquartile range, 4-6). Recurrence occurred in 7 of 78 patients (9%; MGIN, n = 6; HGIN, n = 1); all lesions were managed with RFA. Four other patients (5%) had progression (to HGIN, n = 1; submucosal esophageal squamous cell carcinoma, n = 3). During follow-up protocol violations occurred in 46 of 78 patients (59%). Of the 12 treatment failures, progression occurred in 6. Overall, 2 patients developed subepithelial disease that was not visible after Lugol's endoscopy. Based on post-hoc analysis, the pink color sign at baseline (a pink color change after Lugol's endoscopy) significantly predicted failure after RFA. Conclusions: RFA is relatively easy to apply and can efficiently treat large areas with ESCN. Despite protocol violations that may have interfered with the efficacy of RFA in 59% of patients, most patients with CR12 had sustained CR during follow-up. However, some patients progressed to advanced disease and 2 developed subepithelial disease, not visible after Lugol's endoscopy. Based on currently available data, we advise the restriction of the use of RFA for flat MGIN and HGIN without the pink-color sign on Lugol's chromoendoscopy. (Clinical trial registration number: NCT02047305.)