Can optical evaluation distinguish between t1a and t1b esophageal adenocarcinoma: an international expert inter-observer agreement study.

INTRODUCTION: While piecemeal endoscopic mucosal resection (EMR) for T1a oesophageal adenocarcinoma is acceptable, enbloc-R0 excision is advocated for T1b disease as it may offer a potential cure and mitigate recurrence. Thus, distinguishing between T1a and T1b disease is imperative under current treatment paradigms. We sought to ascertain whether expert Barrett's endoscopists were able to make this distinction based on optical evaluation. METHODS: Sixty sets of endoscopic images of histologically confirmed high grade dysplasia (HGD), T1a and T1b disease (n=20 for each) were compiled from consecutive patients at a single institution. Each set contained four images, and were standardized to include an overview, a close-up in high-definition white light, a near-focus magnification image, and a narrow-band image. Experts were invited to predict histology for each set. RESULTS: 19 experts from 8 countries (Australia, USA, Italy, Netherlands, Germany, Canada, Belgium, and Portugal) participated. The majority had been practicing for >20 years, with a median annual case volume for Barrett's EMR of 50 (IQR 18-75), and Barrett's ESD of 25 (IQR 10-45). Oesophageal adenocarcinoma (T1a/b) could be distinguished from HGD, with a pooled sensitivity of 89.1% (95% CI:84.7-93.4. When predicting T-stage for T1b adenocarcinoma cases, pooled sensitivity was 43.8% (95% CI:29.9-57.7). Fleiss' kappa was 0.421 (95% CI:0.399-0.442, P<0.001), indicating fair-to-moderate agreement. CONCLUSIONS: Expert Barrett's endoscopists can reliably differentiate T1a/T1b oesophageal adenocarcinoma from HGD. Although there is fair-to-moderate agreement for T-staging, T1b disease cannot be reliably distinguished from T1a disease. This may have implications on clinical decision making and selection of endoscopic treatment methods.

Hemospray® (hemostatic powder TC-325) as monotherapy for acute gastrointestinal bleeding: a multicenter prospective study.

Background: Hemostatic powders are used as second-line treatment in acute gastrointestinal (GI) bleeding (AGIB). Increasing evidence supports the use of TC-325 as monotherapy in specific scenarios. This prospective, multicenter study evaluated the performance of TC-325 as monotherapy for AGIB. Methods: Eighteen centers across Europe and USA contributed to a registry between 2016 and 2022. Adults with AGIB were eligible, unless TC-325 was part of combined hemostasis. The primary endpoint was immediate hemostasis. Secondary outcomes were rebleeding and mortality. Associations with risk factors were investigated (statistical significance at P≤0.05). Results: One hundred ninety patients were included (age 51-81 years, male: female 2:1), with peptic ulcer (n=48), upper GI malignancy (n=79), post-endoscopic treatment hemorrhage (n=37), and lower GI lesions (n=26). The primary outcome was recorded in 96.3% (95% confidence interval [CI]: 92.6-98.5) with rebleeding in 17.4% (95%CI 11.9-24.1); 9.9% (95%CI 5.8-15.6) died within 7 days, and 21.7% (95%CI 15.6-28.9) within 30 days. Regarding peptic ulcer, immediate hemostasis was achieved in 88% (95%CI 75-95), while 26% (95%CI 13-43) rebled. Higher ASA score was associated with mortality (OR 23.5, 95%CI 1.60-345; P=0.02). Immediate hemostasis was achieved in 100% of cases with malignancy and post-intervention bleeding, with rebleeding in 17% and 3.1%, respectively. Twenty-six patients received TC-325 for lower GI bleeding, and in all but one the primary outcome was achieved. Conclusions: TC-325 monotherapy is safe and effective, especially in malignancy or post-endoscopic intervention bleeding. In patients with peptic ulcer, it could be helpful when the primary treatment is unfeasible, as bridge to definite therapy.

Extracellular vesicles in pancreatic cancer: a new era in precision medicine.

Pancreatic cancer (PC) is a lethal disease that presents a considerable challenge to healthcare providers and patients, given its low survival rate. However, recent advancements in precision medicine and innovative technologies have transformed the management of this disease. Among these advancements, extracellular vesicles (EVs) have emerged as crucial players in cancer progression. In PC, EVs play a pivotal role by facilitating cell-cell communication, impeding immune response, promoting cancer cell proliferation and survival, and supporting angiogenesis and chemoresistance. Cancer-derived EVs have a distinct oncogenic composition supporting tumour development and progression. Hence, they are critical biomarker candidates for various cancers, including PC. Notably, EVs can be isolated from diverse biological fluids such as blood, urine, and saliva, making them an ideal minimally invasive diagnostic and monitoring tool for PC patients. Despite the promising findings in the field of EVs, clinical validation as biomarkers is lacking. Furthermore, EVs being biocompatible, can act as drug carriers, delivering therapeutic molecules directly to cancer cells while minimizing toxicity to healthy cells. Therefore, understanding the role of EVs as biomarkers and their potential as drug cargo vehicles may revolutionise early detection, prognostication, and treatment in cancer. This mini-review summarises the latest understanding of their role in intercellular communication, involvement as potential biomarkers and drug carriers.

Stratification of Barrett's esophagus surveillance based on p53 immunohistochemistry: a cost-effectiveness analysis by an international collaborative group.

BACKGROUND: Surveillance of nondysplastic Barrett's esophagus (NDBE) is recommended to identify progression to dysplasia; however, the most cost-effective strategy remains unclear. Mutation of TP53 or aberrant expression of p53 have been associated with the development of dysplasia in BE. We sought to determine if surveillance intervals for BE could be stratified based on p53 expression. METHODS: A Markov model was developed for NDBE. Patients with NDBE underwent p53 immunohistochemistry (IHC) and those with abnormal p53 expression underwent surveillance endoscopy at 1 year, while patients with normal p53 expression underwent surveillance in 3 years. Patients with dysplasia underwent endoscopic therapy and surveillance. RESULTS: On base-case analysis, the strategy of stratifying surveillance based on abnormal p53 IHC was cost-effective relative to conventional surveillance and a natural history model, with an incremental cost-effectiveness ratio (ICER) of $8258 for p53 IHC-based surveillance. Both the conventional and p53-stratified surveillance strategies dominated the natural history model. On probabilistic sensitivity analysis, the p53 IHC strategy ($28 652; 16.78 quality-adjusted life years [QALYs]) was more cost-effective than conventional surveillance ($25 679; 16.17 QALYs) with a net monetary benefit of $306 873 compared with conventional surveillance ($297 642), with an ICER <$50 000 in 96% of iterations. The p53-stratification strategy was associated with a 14% reduction in the overall endoscopy burden and a 59% increase in dysplasia detection. CONCLUSION: A surveillance strategy for BE based on abnormal p53 IHC is cost-effective relative to a conventional surveillance strategy and is likely to be associated with higher rates of dysplasia diagnosis.

Computer-aided diagnosis improves characterization of Barrett's neoplasia by general endoscopists (with video).

BACKGROUND AND AIMS: Characterization of visible abnormalities in patients with Barrett's esophagus (BE) can be challenging, especially for inexperienced endoscopists. This results in suboptimal diagnostic accuracy and poor interobserver agreement. Computer-aided diagnosis (CADx) systems may assist endoscopists. We aimed to develop, validate, and benchmark a CADx system for BE neoplasia. METHODS: The CADx system received pretraining with ImageNet and then consecutive domain-specific pretraining with GastroNet, which includes 5 million endoscopic images. It was subsequently trained and internally validated using 1758 narrow-band imaging (NBI) images of early BE neoplasia (352 patients) and 1838 NBI images of nondysplastic BE (173 patients) from 8 international centers. CADx was tested prospectively on corresponding image and video test sets with 30 cases (20 patients) of BE neoplasia and 60 cases (31 patients) of nondysplastic BE. The test set was benchmarked by 44 general endoscopists in 2 phases (phase 1, no CADx assistance; phase 2, with CADx assistance). Ten international BE experts provided additional benchmark performance. RESULTS: Stand-alone sensitivity and specificity of the CADx system were 100% and 98% for images and 93% and 96% for videos, respectively. CADx outperformed general endoscopists without CADx assistance in terms of sensitivity (P = .04). Sensitivity and specificity of general endoscopists increased from 84% to 96% and 90% to 98% with CAD assistance (P < .001). CADx assistance increased endoscopists' confidence in characterization (P < .001). CADx performance was similar to that of the BE experts. CONCLUSIONS: CADx assistance significantly increased characterization performance of BE neoplasia by general endoscopists to the level of expert endoscopists. The use of this CADx system may thereby improve daily Barrett surveillance.

Adherence to endoscopic surveillance guidelines for patients with inflammatory bowel disease: An Australian cohort study.

BACKGROUND AND AIM: Patients with inflammatory bowel disease have an increased risk of developing colorectal cancer as compared with the general population. Endoscopic surveillance to detect early dysplastic changes is advised by several published clinical guidelines, which provide recommendations as to the timing and performance of surveillance procedures. There is a paucity of data as to adherence with these guidelines in clinical practice. METHODS: A longitudinal inception cohort study of all new patients diagnosed with inflammatory bowel disease across a service network of Australian hospitals between January 2005 and June 2014, with continuous follow-up in a gastroenterology clinic until December 31, 2022. Patients were included if they warranted surveillance according to the Australian guidelines. Adherence to guidelines and technical and quality measures were reported. RESULTS: A total of 136 patients were included, and a total of 263 surveillance procedures were performed. Ninety-five patients (70%) had their first surveillance colonoscopy within the correct time interval. Fifty patients (37%) were completely adherent to guidelines with respect to timing of all surveillance procedure. The overall dysplasia detection rate for surveillance procedures was 10%. Chromoendoscopy was only performed in 16% of procedures. CONCLUSIONS: Adherence to endoscopic surveillance guidelines with regard to timing of procedures and the utilization of chromoendoscopy is poor. Further clinician education, promotion of the surveillance guidelines and incorporation of chromoendoscopy training as part of the national colonoscopy training program may improve adherence to guidelines.

Incidence, prevalence and clinical management of achalasia since the introduction of high-resolution manometry in Western Australia.

BACKGROUND: Epidemiological studies in achalasia and its clinical management in Australia are limited. AIMS: To determine the prevalence and trends in incidence rates and describe the types of treatment stratified by subtypes of achalasia. METHODS: A retrospective observational study was conducted at a single site that offers a state-wide high-resolution manometry (HRM) service in Western Australia (WA). Patients (aged ≥ 18 years) newly diagnosed with achalasia based on HRM findings between 2012 and 2021 were extracted from the HRM database. The crude incidence rate and age-standardised incidence rate (ASIR) along with the 2021-point prevalence were calculated. Trends were assessed by the Kendall τb test. The patients' initial and subsequent treatment modalities were described. RESULTS: A total of 296 new cases were identified, and the median age at diagnosis was 56 years. The patient's median age, sex and year of the first treatment did not vary significantly with the subtypes. The lowest and highest ASIR (cases/100 000 person-years) were 0.8 in 2012 and 2.1 in 2021, respectively. Only type 2 achalasia showed a significant increasing trend (P = 0.009). The 2021-point prevalence was 16.9 cases/100 000 people and increased with age. Pneumatic balloon dilatation (PBD) was the most common treatment for types 1 and 2, while laparoscopic Heller myotomy was most common for type 3. Peroral endoscopic myotomy (POEM) has become common in the past 5 years. CONCLUSION: The ASIR of type 2 achalasia significantly increased in WA. PBD was most commonly performed, although peroral endoscopic myotomy has recently increased as a preferred treatment option.

Quality indicators in Barrett's endoscopy: Best is yet to come.

There is growing interest in establishing quality indicators (QIs) for endoscopic screening and surveillance in Barrett's esophagus (BE). QIs are objective, measurable, and evidence-based metrics that are applicable in a health-care setting to monitor a process and identify key performance indicators (KPIs) to achieve defined goals. In the Barrett's endoscopy setting, QIs can offer a standardized approach to monitor and maintain high-quality endoscopy for BE screening and surveillance that will allow measuring performance of an endoscopist as an individual, a group, or a facility. Since BE is an endoscopically identifiable premalignant condition with histological corroboration, adherence to QIs is paramount for the early and accurate detection of dysplasia and neoplasia. It is the holy grail for BE screening and surveillance. Although several suggested QIs for Barrett's endoscopy exist, issues remain in determining the most appropriate ones. These issues include inconsistent use of terminology, unclear definitions, and a scarcity of studies linking these QIs with relevant patient outcomes, making it difficult for clinicians to understand the concept and clinical importance. Hence, there is an urgent need to determine what should constitute appropriate QIs for Barrett's endoscopy, clearly define items used in the QIs, and identify ways to measure these KPIs. Ultimately, well-defined and validated QIs will contribute to clinically effective, safe, timely, and patient-focused care. In this review, we summarize recent literature and discuss four proposed QIs: (i) neoplasia detection rate; (ii) postendoscopy Barrett's neoplasia; (iii) Barrett's inspection time; and (iv) adherence to the Seattle biopsy protocol.

Prevalence of gastrointestinal malignancy in non-anemic iron deficiency and significance for endoscopic screening: A Western Australian multicenter cohort study.

BACKGROUND AND AIM: There is a paucity of evidence regarding non-anemic iron deficiency as a predictor for colorectal cancer and therefore the indication for endoscopic evaluation. This study explores the rates of malignancy in adults with iron deficiency with and without anemia. METHODS: A retrospective multicenter diagnostic cohort study was conducted across two Australian health services. All cases that underwent both esophagogastroduodenoscopy and colonoscopy between September 1, 2018, and December 31, 2019, for the investigation of iron deficiency were included, and the cohort was divided into anemic and non-anemic arms. Multivariate binomial logistic regression was performed to establish clinical characteristics associated with neoplasia. RESULTS: Five hundred eighty-four patients underwent endoscopic evaluation over a 16-month period. There was a significantly higher rate of malignancy in the iron deficiency anemia arm as compared with those without anemia (8.76% vs 1.20%, P < 0.01). Gastrointestinal pathology to account for iron deficiency was identified in > 60% of the total cohort. The presence of anemia (odds ratio [OR] 6.87, P < 0.01) and male gender (OR 3.01, P = 0.01) were significant predictors of malignancy. CONCLUSION: This study demonstrates that anemic iron deficiency confers a significantly greater risk of gastrointestinal cancer compared with non-anemic iron deficiency. Additionally, over 60% of patients had gastrointestinal pathology to account for iron deficiency overall, supporting the need to perform baseline endoscopy in patients with iron deficiency.

Towards a robust and compact deep learning system for primary detection of early Barrett's neoplasia: Initial image-based results of training on a multi-center retrospectively collected data set.

INTRODUCTION: Endoscopic detection of early neoplasia in Barrett's esophagus is difficult. Computer Aided Detection (CADe) systems may assist in neoplasia detection. The aim of this study was to report the first steps in the development of a CADe system for Barrett's neoplasia and to evaluate its performance when compared with endoscopists. METHODS: This CADe system was developed by a consortium, consisting of the Amsterdam University Medical Center, Eindhoven University of Technology, and 15 international hospitals. After pretraining, the system was trained and validated using 1.713 neoplastic (564 patients) and 2.707 non-dysplastic Barrett's esophagus (NDBE; 665 patients) images. Neoplastic lesions were delineated by 14 experts. The performance of the CADe system was tested on three independent test sets. Test set 1 (50 neoplastic and 150 NDBE images) contained subtle neoplastic lesions representing challenging cases and was benchmarked by 52 general endoscopists. Test set 2 (50 neoplastic and 50 NDBE images) contained a heterogeneous case-mix of neoplastic lesions, representing distribution in clinical practice. Test set 3 (50 neoplastic and 150 NDBE images) contained prospectively collected imagery. The main outcome was correct classification of the images in terms of sensitivity. RESULTS: The sensitivity of the CADe system on test set 1 was 84%. For general endoscopists, sensitivity was 63%, corresponding to a neoplasia miss-rate of one-third of neoplastic lesions and a potential relative increase in neoplasia detection of 33% for CADe-assisted detection. The sensitivity of the CADe system on test sets 2 and 3 was 100% and 88%, respectively. The specificity of the CADe system varied for the three test sets between 64% and 66%. CONCLUSION: This study describes the first steps towards the establishment of an unprecedented data infrastructure for using machine learning to improve the endoscopic detection of Barrett's neoplasia. The CADe system detected neoplasia reliably and outperformed a large group of endoscopists in terms of sensitivity.

Factors influencing participation in randomised clinical trials among patients with early Barrett's neoplasia: a multicentre interview study.

OBJECTIVES: Strong recruitment and retention into randomised controlled trials involving invasive therapies is a matter of priority to ensure better achievement of trial aims. The BRIDE (Barrett's Randomised Intervention for Dysplasia by Endoscopy) Study investigated the feasibility of undertaking a multicentre randomised controlled trial comparing argon plasma coagulation and radiofrequency ablation, following endoscopic resection, for the management of early Barrett's neoplasia. This paper aims to identify factors influencing patients' participation in the BRIDE Study and determine their views regarding acceptability of a potential future trial comparing surgery with endotherapy. DESIGN: A semistructured telephone interview study was performed, including both patients who accepted and declined to participate in the BRIDE trial. Interview data were analysed using the constant comparison approach to identify recurring themes. SETTING: Interview participants were recruited from across six UK tertiary centres where the BRIDE trial was conducted. PARTICIPANTS: We interviewed 18 participants, including 11 participants in the BRIDE trial and 7 who declined. RESULTS: Four themes were identified centred around interviewees' decision to accept or decline participation in the BRIDE trial and a potential future trial comparing endotherapy with surgery: (1) influence of the recruitment process and participant-recruiter relationship; (2) participants' views of the design and aim of the study; (3) conditional altruism as a determining factor and (4) participants' perceptions of surgical risks versus less invasive treatments. CONCLUSION: We identified four main influences to optimising recruitment and retention to a randomised controlled trial comparing endotherapies in patients with early Barrett's-related neoplasia. These findings highlight the importance of qualitative research to inform the design of larger randomised controlled trials.

The effect of procedural time on dysplasia detection rate during endoscopic surveillance of Barrett's esophagus.

BACKGROUND : Endoscopic surveillance of Barrett's esophagus (BE) with Seattle protocol biopsies is time-consuming and inadequately performed in routine practice. There is no recommended procedural time for BE surveillance. We investigated the duration of surveillance procedures with adequate tissue sampling and effect on dysplasia detection rate (DDR). METHODS : We performed post hoc analysis from the standard arm of a crossover randomized controlled trial recruiting patients with BE (≥C2 and/or ≥M3) and no clearly visible dysplastic lesions. After inspection with white-light imaging, targeted biopsies of subtle lesions and Seattle protocol biopsies were performed. Procedure duration and biopsy number were stratified by BE length. The effect of endoscopy-related variables on DDR was assessed by multivariable logistic regression. RESULTS : Of 142 patients recruited, 15 (10.6 %) had high grade dysplasia/intramucosal cancer and 15 (10.6 %) had low grade dysplasia. The median procedural time was 16.5 minutes (interquartile range 14.0-19.0). Endoscopy duration increased by 0.9 minutes for each additional 1 cm of BE length. Seattle protocol biopsies had higher sensitivity for dysplasia than targeted biopsies (86.7 % vs. 60.0 %; P = 0.045). Longer procedural time was associated with increased likelihood of dysplasia detection on quadrantic biopsies (odds ratio [OR] 1.10, 95 %CI 1.00-1.20, P = 0.04), and for patients with BE > 6 cm also on targeted biopsies (OR 1.21, 95 %CI 1.04-1.40; P = 0.01). CONCLUSIONS : In BE patients with no clearly visible dysplastic lesions, longer procedural time was associated with increased likelihood of dysplasia detection. Adequate time slots are required to perform good-quality surveillance and maximize dysplasia detection.

Wide-area transepithelial sampling with computer-assisted analysis to detect high grade dysplasia and cancer in Barrett's esophagus: a multicenter randomized study.

BACKGROUND: Current surveillance for Barrett's esophagus (BE), consisting of four-quadrant random forceps biopsies (FBs), has an inherent risk of sampling error. Wide-area transepithelial sampling (WATS) may increase detection of high grade dysplasia (HGD) and esophageal adenocarcinoma (EAC). In this multicenter randomized trial, we aimed to evaluate WATS as a substitute for FB. METHODS: Patients with known BE and a recent history of dysplasia, without visible lesions, at 17 hospitals were randomized to receive either WATS followed by FB or vice versa. All WATS samples were examined, with computer assistance, by at least two experienced pathologists at the CDx Diagnostics laboratory. Similarly, all FBs were examined by two expert pathologists. The primary end point was concordance/discordance for detection of HGD/EAC between the two techniques. RESULTS: 172 patients were included, of whom 21 had HGD/EAC detected by both modalities, 18 had HGD/EAC detected by WATS but missed by FB, and 12 were detected by FB but missed by WATS. The detection rate of HGD/EAC did not differ between WATS and FB (P = 0.36). Using WATS as an adjunct to FB significantly increased the detection of HGD/EAC vs. FB alone (absolute increase 10 % [95 %CI 6 % to 16 %]). Mean procedural times in minutes for FB alone, WATS alone, and the combination were 6.6 (95 %CI 5.9 to 7.1), 4.9 (95 %CI 4.1 to 5.4), and 11.2 (95 %CI 10.5 to 14.0), respectively. CONCLUSIONS: Although the combination of WATS and FB increases dysplasia detection in a population of BE patients enriched for dysplasia, we did not find a statistically significant difference between WATS and FB for the detection of HGD/EAC as single modality.

Early outcomes following EndoFLIP-tailored peroral endoscopic myotomy (POEM): the establishment of POEM services in two UK centers.

Peroral endoscopic myotomy (POEM) is a safe and effective minimally invasive treatment for achalasia. Postoperative reflux rates remain high. The functional luminal imaging probe (FLIP) allows intraoperative measurement of lower esophageal distensibility during POEM. In theory, this enables a tailoring of myotomies to ensure adequate distensibility while minimizing postoperative reflux risk. Two prospectively collected POEM databases were analyzed from two UK tertiary upper GI centers. The operators in each center used FLIP measurements to ensure adequate myotomy. Outcome measures included Eckardt score (where <3 indicated clinical success) and proton-pump inhibitor use (PPI), collected at the first postoperative appointment. Length of stay was recorded as were complications. In all, 142 patients underwent POEM between 2015 and 2019. Overall, 90% (128/142) had postoperative Eckardt scores of <3 at 6 weeks. Clinical success improved to 93% (66/71) in the latter half of each series with a significantly higher rate of complete symptom resolution (53 versus 26%, P = 0.003). In all, 79% of the poor responders had previous interventions compared with 55% of responders (P = 0.09). Median post-myotomy distensibility index was 4.0 mm2/mmHg in responders and 2.9 in nonresponders (P = 0.16). Myotomy length of <7 cm was associated with 93% clinical success and 40% post op PPI use compared with 60% PPI use with longer myotomies. There were two type IIIa, two type IIIb, and one IV Clavien-Dindo complications. This is the largest series of endoluminal functional lumen imaging probe (EndoFLIP)-tailored POEM in the UK to date. The shorter myotomies, allowed through EndoFLIP tailoring, remained clinically effective at 6 weeks. Complete symptom response rates improved in the latter half of each series. More data will be needed from high-volume collaborations to decipher optimal myotomy profiles based on EndoFLIP parameters.

Comparative cost-effectiveness of three post-radiofrequency ablation surveillance intervals for Barrett's esophagus.

Background and study aims Radiofrequency ablation (RFA) for dysplastic Barrett's esophagus (BE) has resulted in a paradigm shift in the management of BE. Despite widespread adoption of RFA, the optimal surveillance interval of the ablated zone is unclear. Methods A patient-level discrete time cycle Markov model was developed to model clinical surveillance strategies post-RFA for BE. Three surveillance strategies were examined: the American College of Gastroenterology (ACG) strategy based on ACG guidelines for post-RFA surveillance, the Cotton strategy based on data from the USA and UK RFA registries, and the UK strategy in line with surveillance strategies in UK centers. Monte-Carlo deterministic and probabilistic analyses were performed over 10,000 iterations (i. e., representing 10,000 patient journeys) and sensitivity analyses were carried out on the variables used in the model. Results On base-case analysis, the ACG strategy was the most cost-effective strategy, at a mean cost of £â€Š11,733 ($ 16,396) (standard deviation (SD) 1520.15) and a mean effectiveness of 12.86 (SD 0.07) QALYs. Probabilistic sensitivity analysis demonstrated that the ACG model was the most cost-effective strategy with a net monetary benefit (NMB) of £â€Š5,136 ($ 7177) (SD 241) compared to the UK strategy and a NMB of £â€Š7017 ($ 9,806) (SD 379) compared to the Cotton strategy. At a willingness to pay (WTP) threshold of £â€Š20,000 ($ 27,949), the ACG model was superior to the other strategies as the most cost-effective strategy. Conclusions A post-RFA surveillance strategy based on the ACG guidelines seems to be the most cost-effective surveillance option.

A new artificial intelligence system successfully detects and localises early neoplasia in Barrett's esophagus by using convolutional neural networks.

BACKGROUND AND AIMS: Seattle protocol biopsies for Barrett's Esophagus (BE) surveillance are labour intensive with low compliance. Dysplasia detection rates vary, leading to missed lesions. This can potentially be offset with computer aided detection. We have developed convolutional neural networks (CNNs) to identify areas of dysplasia and where to target biopsy. METHODS: 119 Videos were collected in high-definition white light and optical chromoendoscopy with i-scan (Pentax Hoya, Japan) imaging in patients with dysplastic and non-dysplastic BE (NDBE). We trained an indirectly supervised CNN to classify images as dysplastic/non-dysplastic using whole video annotations to minimise selection bias and maximise accuracy. The CNN was trained using 148,936 video frames (31 dysplastic patients, 31 NDBE, two normal esophagus), validated on 25,161 images from 11 patient videos and tested on 264 iscan-1 images from 28 dysplastic and 16 NDBE patients which included expert delineations. To localise targeted biopsies/delineations, a second directly supervised CNN was generated based on expert delineations of 94 dysplastic images from 30 patients. This was tested on 86 i-scan one images from 28 dysplastic patients. FINDINGS: The indirectly supervised CNN achieved a per image sensitivity in the test set of 91%, specificity 79%, area under receiver operator curve of 93% to detect dysplasia. Per-lesion sensitivity was 100%. Mean assessment speed was 48 frames per second (fps). 97% of targeted biopsy predictions matched expert and histological assessment at 56 fps. The artificial intelligence system performed better than six endoscopists. INTERPRETATION: Our CNNs classify and localise dysplastic Barrett's Esophagus potentially supporting endoscopists during surveillance.

Narrow-band imaging for the diagnosis of nonerosive reflux disease: an international, multicenter, randomized controlled trial.

BACKGROUND AND AIMS: We examined the accuracy of narrow-band imaging (NBI) findings in nonerosive reflux disease (NERD) patients compared with control subjects and the impact of proton pump inhibitor (PPI) therapy on these mucosal changes in a multicenter, double-blind, randomized controlled trial. METHODS: NERD patients (typical symptoms using a validated GERD questionnaire, absence of erosive esophagitis, and abnormal 48-hour pH study) and control subjects underwent high-definition white-light endoscopy followed by NBI and biopsy sampling of the distal esophagus. Then, NERD patients were randomized to esomeprazole 40 mg/day or placebo for 8 weeks, followed by repeat endoscopy. The presence of distal esophageal mucosal changes on NBI were recorded at baseline and after treatment: intrapapillary capillary loops (IPCLs; number, dilation, and tortuosity), microerosions, increased vascularity, columnar islands, and ridge/villous pattern (RVP) above the squamocolumnar junction. RESULTS: Of 122 screened, 21 NERD and 21 control subjects were identified (mean age, 49.5 ± 14.6 years; 62% men; and 85% white). The combination of IPCL tortuosity, RVP, and microerosions (62% vs 19%, P < .05) had a high specificity (86%) and moderate sensitivity (60%) for NERD with an area under the curve of .74. In 10 NERD patients treated with PPIs, resolution of microerosions was most significant (P = .047) compared with placebo (n = 11). RVP resolved in all NERD patients after therapy (P = .02) and correlated with acid exposure time (P = .004). Papillary length (P = .02) and basal cell thickness (P = .02) significantly correlated with a combination of IPCL tortuosity, RVP, and microerosions. CONCLUSIONS: In this randomized controlled trial, RVP on NBI demonstrated a high specificity, correlated with acid exposure time, and improved with PPI therapy, suggesting that it could be used as a surrogate marker for diagnosis of NERD. (Clinical trial registration number: NCT02081404.).

Study to investigate the prevalence of human papillomavirus in Barrett's oesophagus using a novel screening methodology.

INTRODUCTION: Human papillomavirus (HPV) is strongly associated with Barrett's dysplasia and oesophageal cancer suggesting a role in carcinogenesis. HPV persistence predicts treatment failure after endotherapy for Barrett's dysplasia. This pilot study applies a novel HPV screening tool (previously only used in the oropharynx) to detect HPV DNA directly and determine the prevalence rates in Barrett's oesophagus (BO). METHOD: DNA was extracted from 20 formalin-fixed BO samples. HPV DNA was detected using real-time PCR and gel electrophoresis. RESULTS: 5 out of 20 patients were identified as positive for HPV. Prevalence was 25% in patients with BO. CONCLUSION: This method can be used in BO's tissue to determine HPV infection. Adoption of this as a screening test could potentially revolutionise future research in this area. If a clear link between HPV and Barrett's dysplasia can be confirmed, this qPCR method has the potential to aid in monitoring and/or dysplasia detection by stratifying those most at risk and aid in the development of new therapies.

Rio de Janeiro Global Consensus on Landmarks, Definitions, and Classifications in Barrett's Esophagus: World Endoscopy Organization Delphi Study.

BACKGROUND & AIMS: Despite the significant advances made in the diagnosis and treatment of Barrett's esophagus (BE), there is still a need for standardized definitions, appropriate recognition of endoscopic landmarks, and consistent use of classification systems. Current controversies in basic definitions of BE and the relative lack of anatomic knowledge are significant barriers to uniform documentation. We aimed to provide consensus-driven recommendations for uniform reporting and global application. METHODS: The World Endoscopy Organization Barrett's Esophagus Committee appointed leaders to develop an evidence-based Delphi study. A working group of 6 members identified and formulated 23 statements, and 30 internationally recognized experts from 18 countries participated in 3 rounds of voting. We defined consensus as agreement by ≥80% of experts for each statement and used the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) tool to assess the quality of evidence and the strength of recommendations. RESULTS: After 3 rounds of voting, experts achieved consensus on 6 endoscopic landmarks (palisade vessels, gastroesophageal junction, squamocolumnar junction, lesion location, extraluminal compressions, and quadrant orientation), 13 definitions (BE, hiatus hernia, squamous islands, columnar islands, Barrett's endoscopic therapy, endoscopic resection, endoscopic ablation, systematic inspection, complete eradication of intestinal metaplasia, complete eradication of dysplasia, residual disease, recurrent disease, and failure of endoscopic therapy), and 4 classification systems (Prague, Los Angeles, Paris, and Barrett's International NBI Group). In round 1, 18 statements (78%) reached consensus, with 12 (67%) receiving strong agreement from more than half of the experts. In round 2, 4 of the remaining statements (80%) reached consensus, with 1 statement receiving strong agreement from 50% of the experts. In the third round, a consensus was reached on the remaining statement. CONCLUSIONS: We developed evidence-based, consensus-driven statements on endoscopic landmarks, definitions, and classifications of BE. These recommendations may facilitate global uniform reporting in BE.