Trends in body mass index in the pre-dolutegravir period in South Africa.

Background: Antiretroviral therapy (ART) is associated with weight gain, but this has been shown to be more marked with dolutegravir and other integrase strand transfer inhibitors. Objectives: We studied weight gain in people living with HIV (PLWH) on ART compared to the general population in the period before dolutegravir was introduced in a rural South African cohort. Method: Longitudinal analysis of the Ndlovu Cohort Study including 36-48 months' follow-up data. From 2014 to 2019, data were collected annually in Limpopo, rural South Africa. Linear mixed models using HIV status, demographics, ART use and cardiovascular risk factors were used to estimate trends in body mass index (BMI) over time. Results: In total, 1518 adult, non-pregnant participants were included, of whom 518 were PLWH on ART (79.8%), 135 PLWH not yet on ART (20.2%) and 865 HIV-negative. HIV-negative participants had significantly higher BMIs than PLWH on ART at all study visits. There was a significant increase in BMI in all subgroups after 36 months (PLWH on ART, BMI +1.2 kg/m2, P < 0.001; PLWH not on ART, BMI +1.8 kg/m2, P < 0.001 and HIV-negative, BMI +1.3 kg/m2, P < 0.001). Conclusion: The increase in BMI in PLWH and HIV-negative participants is a serious warning signal as obesity results in morbidity and mortality.

Anti-reflux mucosectomy for gastroesophageal reflux disease: efficacy and the mechanism of action.

Previous studies suggest that anti-reflux mucosectomy (ARMS) is effective in reducing reflux symptoms and total acid exposure, although the mechanism is unknown. Our objective was to investigate the effect of ARMS on reflux parameters and mechanism of action. METHODS: Gastroesophageal reflux (GERD) patients with insufficient symptom control despite twice daily proton pump inhibitor (PPI) underwent a piecemeal multiband mucosectomy of 50% of the circumference of the esophago-gastric-junction (EGJ), extending 2cm into the cardia. The primary endpoint was the total number of reflux episodes during 24-h pH-impedance studies. RESULTS: 11 patients were treated (8 men, age 37 (32-57) years), one patient is lost to follow-up after treatment. ARMS reduced the total number of reflux episodes from 74 (50-82) to 37 (28-66) p=0.008) and total acid exposure from 8.7% (6.4-12.7) to 5.3% (3.5-6.7) (p=0.008). Treatment reduced the number of transient lower esophageal sphincter relaxations (TLESRs) (from 4 (1-8) to 2 (1-4), p=0.027) during a 90-minute postprandial period. Reflux symptoms were reduced substantially (from 3.6 (3.6-3.9) to 1.6 (0.7-2.7), p=0.007). Treatment did not increase dysphagia (Brief Esophageal Dysphagia Questionnaire)of 8.2 (±7.3) to 8.5 (±6.5) (p=0.879). Impedance planimetry showed no changes in EGJ distensibility after treatment (4.4 (±2.1) mm2/mmHg to 4.3 (±2.2) mm2/mmHg), p=0.952). One delayed post-procedural bleeding (10%, (1/10)) occurred requiring repeat endoscopy, no strictures developed. CONCLUSION: ARMS is an effective treatment option in PPI refractory GERD patients reducing acid exposure, reflux episodes and symptoms. While its working mechanism could not be explained by a difference in distensibility, a reduction in TLSERs might play a role.

The use of a real-time computer-aided detection system for visible lesions in the Barrett's esophagus during live endoscopic procedures, a pilot study.

BACKGROUND AND AIMS: In this pilot study we evaluated performance of a recently developed computer-aided detection (CADe) system for Barrett's neoplasia during live endoscopic procedures. METHODS: 15 patients with and 15 without a visible lesion were included in this study. A CAD assisted workflow was employed that included: a slow pullback video recording of the entire Barrett's segment with live CADe assistance, followed by CADe assisted level-based video recordings every 2cm of the Barrett's segment. Outcomes were per patient and per level diagnostic accuracy of the CAD assisted workflow, where the primary outcome was per patient in-vivo CADe sensitivity. RESULTS: In the per patient analyses, the CADe system detected all visible lesions (sensitivity 100%). Per patient CADe specificity was 53%. Per-level sensitivity and specificity of the CADe assisted workflow were 100% and 73%, respectively. CONCLUSION: In this pilot study, the CADe system detected all potentially neoplastic lesions in Barrett's esophagus comparable to an expert endoscopist. Continued refinement of the system may improve specificity. External validation in larger multicenter studies is planned.

Towards personalized management of early esophageal adenocarcinoma.

PURPOSE OF REVIEW: This review aims to discuss recent advancements in the endoscopic management of early esophageal adenocarcinoma (T1 EAC). RECENT FINDINGS: Patients with high-risk EAC (defined by the presence of deep submucosal invasion, and/or lymphovascular invasion, and/or poor differentiation) have a higher risk of lymph node metastases than those with low-risk EAC. However, more recent, endoscopically-focused studies report a lower risk of lymph node metastases and distant metastases for high-risk EAC than previously assumed. Instead of referring all high-risk EAC patients for esophagectomy after a radical endoscopic resection, an alternative approach involving regular upper endoscopy with endoscopic ultrasound may allow for detection of intra-luminal recurrence and lymph node metastases at an early and potentially curable stage. SUMMARY: Endoscopic resection of mucosal and submucosal EAC might prove to be safe and curative for selected cases in the future, when followed by a strict follow-up protocol. Despite the promising results of preliminary studies, there is an ongoing need for personalized strategies and new risk stratification methods to decide on the best management for individual patients with high-risk T1 EAC.

Phenotypic immune characterization of gastric and esophageal adenocarcinomas reveals profound immune suppression in esophageal tumor locations.

Background: Tumors in the distal esophagus (EAC), gastro-esophageal junction including cardia (GEJAC), and stomach (GAC) develop in close proximity and show strong similarities on a molecular and cellular level. However, recent clinical data showed that the effectiveness of chemo-immunotherapy is limited to a subset of GEAC patients and that EACs and GEJACs generally benefit less from checkpoint inhibition compared to GACs. As the composition of the tumor immune microenvironment drives response to (immuno)therapy we here performed a detailed immune analysis of a large series of GEACs to facilitate the development of a more individualized immunomodulatory strategy. Methods: Extensive immunophenotyping was performed by 14-color flow cytometry in a prospective study to detail the immune composition of untreated gastro-esophageal cancers (n=104) using fresh tumor biopsies of 35 EACs, 38 GEJACs and 31 GACs. The immune cell composition of GEACs was characterized and correlated with clinicopathologic features such as tumor location, MSI and HER2 status. The spatial immune architecture of a subset of tumors (n=30) was evaluated using multiplex immunohistochemistry (mIHC) which allowed us to determine the tumor infiltration status of CD3+, CD8+, FoxP3+, CD163+ and Ki67+ cells. Results: Immunophenotyping revealed that the tumor immune microenvironment of GEACs is heterogeneous and that immune suppressive cell populations such as monocytic myeloid-derived suppressor cells (mMDSC) are more abundant in EACs compared to GACs (p<0.001). In contrast, GACs indicated a proinflammatory microenvironment with elevated frequencies of proliferating (Ki67+) CD4 Th cells (p<0.001), Ki67+ CD8 T cells (p=0.002), and CD8 effector memory-T cells (p=0.024). Differences between EACs and GACs were confirmed by mIHC analyses showing lower densities of tumor- and stroma-infiltrating Ki67+ CD8 T cells in EAC compared to GAC (both p=0.021). Discussions: This comprehensive immune phenotype study of a large series of untreated GEACs, identified that tumors with an esophageal tumor location have more immune suppressive features compared to tumors in the gastro-esophageal junction or stomach which might explain the location-specific responses to checkpoint inhibitors in this disease. These findings provide an important rationale for stratification according to tumor location in clinical studies and the development of location-dependent immunomodulatory treatment approaches.

Safety and efficacy of salvage endoscopic submucosal dissection for Barrett's neoplasia recurrence after radiofrequency ablation.

BACKGROUND: This study evaluated the safety and efficacy of salvage endoscopic submucosal dissection (ESD) for Barrett's neoplasia recurrence after radiofrequency ablation (RFA). METHODS: Data from patients at 16 centers were collected for a multicenter retrospective study. Patients who underwent at least one RFA treatment for Barrett's esophagus and thereafter underwent further esophageal ESD for neoplasia recurrence were included. RESULTS: Data from 56 patients who underwent salvage ESD between April 2014 and November 2022 were collected. Immediate complications included one muscular tear (1.8%) treated with stent (Agree classification: grade IIIa). Two transmural perforations (3.6%; treated with clips) and five muscular tears (8.9%; two treated with clips) had no clinical impact and were not considered as adverse events. Seven patients (12.5%) developed strictures (grade IIIa), which were treated with balloon dilation. Histological analysis showed 36 adenocarcinoma, 17 high grade dysplasia, and 3 low grade dysplasia. En bloc and R0 resection rates were 89.3% and 66.1%, respectively. Resections were curative in 33 patients (58.9%), and noncurative in 22 patients (39.3%), including 11 "local risk" (19.6%) and 11 "high risk" (19.6%) resections. At the end of follow-up with a median time of 14 (0-75) months after salvage ESD, and with further endoscopic treatment if necessary (RFA, argon plasma coagulation, endoscopic mucosal resection, ESD), neoplasia remission ratio was 37/53 (69.8%) and the median remission time was 13 (1-75) months. CONCLUSION: In expert hands, salvage ESD was a safe and effective treatment for recurrence of Barrett's neoplasia after RFA treatment.

COMPUTER-AIDED DIAGNOSIS IMPROVES CHARACTERIZATION OF BARRETT'S NEOPLASIA BY GENERAL ENDOSCOPISTS.

BACKGROUND & AIMS: Characterization of visible abnormalities in Barrett esophagus (BE) patients can be challenging, especially for unexperienced endoscopists. This results in suboptimal diagnostic accuracy and poor inter-observer 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 with consecutive domain-specific pretraining with GastroNet which includes 5 million endoscopic images. It was subsequently trained and internally validated using 1,758 narrow-band imaging (NBI) images of early BE neoplasia (352 patients) and 1,838 NBI images of non-dysplastic 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 non-dysplastic BE. The test set was benchmarked by 44 general endoscopists in two 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=0.04). Sensitivity and specificity of general endoscopist increased from 84% to 96% and 90 to 98% with CAD assistance (p<0.001), respectively. CADx assistance increased endoscopists' confidence in characterization (p<0.001). CADx performance was similar to Barrett experts. CONCLUSION: 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.

Management of high risk T1 esophageal adenocarcinoma following endoscopic resection.

High-risk T1 esophageal adenocarcinoma (HR-T1 EAC) is defined as T1 cancer, with one or more of the following histological criteria: submucosal invasion, poorly or undifferentiated cancer, and/or presence of lympho-vascular invasion. Esophagectomy has long been the only available treatment for these HR-T1 EACs and was considered necessary because of a presumed high risk of lymph node metastases up to 46%. However, endoscopic submucosal disscection have made it possible to radically remove HR-T1 EAC, irrespective of size, while leaving the esophageal anatomy intact. Parallel to this development, new publications demonstrated that the risk of lymph node metastases for HR-T1 EAC may be even <24%. Therefore, indications for endoscopic treatment of HR-T1 EAC are being reconsidered and current research aims at finding the optimal management strategy for this indication, where watchful waiting may proof to be an acceptable strategy in selected patients. In this review, we will discuss the latest developments in this field.

Incidence and Prediction of Unrelated Mortality After Successful Endoscopic Eradication Therapy for Barrett's Neoplasia.

BACKGROUND & AIMS: Follow-up (FU) strategies after endoscopic eradication therapy (EET) for Barrett's neoplasia do not consider the risk of mortality from causes other than esophageal adenocarcinoma (EAC). We aimed to evaluate this risk during long-term FU, and to assess whether the Charlson Comorbidity Index (CCI) can predict mortality. METHODS: We included all patients with successful EET from the nationwide Barrett registry in the Netherlands. Data were merged with National Statistics for accurate mortality data. We evaluated annual mortality rates (AMRs, per 1000 person-years) and standardized mortality ratio for other-cause mortality. Performance of the CCI was evaluated by discrimination and calibration. RESULTS: We included 1154 patients with a mean age of 64 years (±9). During median 59 months (p25-p75 37-91; total 6375 person-years), 154 patients (13%) died from other causes than EAC (AMR, 24.1; 95% CI, 20.5-28.2), most commonly non-EAC cancers (n = 58), cardiovascular (n = 31), or pulmonary diseases (n = 26). Four patients died from recurrent EAC (AMR, 0.5; 95% CI, 0.1-1.4). Compared with the general Dutch population, mortality was significantly increased for patients in the lowest 3 age quartiles (ie, age <71 years). Validation of CCI in our population showed good discrimination (Concordance statistic, 0.78; 95% CI, 0.72-0.84) and fair calibration. CONCLUSION: The other-cause mortality risk after successful EET was more than 40 times higher (48; 95% CI, 15-99) than the risk of EAC-related mortality. Our findings reveal that younger post-EET patients exhibit a significantly reduced life expectancy when compared with the general population. Furthermore, they emphasize the strong predictive ability of CCI for long-term mortality after EET. This straightforward scoring system can inform decisions regarding personalized FU, including appropriate cessation timing. (NL7039).

Vertical tumor-positive resection margins and the risk of residual neoplasia after endoscopic resection of Barrett's neoplasia: a nationwide cohort with pathology reassessment.

BACKGROUND: This study evaluated the proportion of patients with residual neoplasia after endoscopic resection (ER) for Barrett's neoplasia with confirmed tumor-positive vertical resection margin (R1v). METHODS: This retrospective cohort study included patients undergoing ER for Barrett's neoplasia with histologically documented R1v since 2008 in the Dutch Barrett Expert Centers. We defined R1v as cancer cells touching vertical resection margins and Rx as nonassessable margins. Reassessment of R1v specimens was performed by experienced pathologists until consensus was reached regarding vertical margins. RESULTS: 101/110 included patients had macroscopically complete resections (17 T1a, 84 T1b), and 99/101 (98%) ER specimens were histologically reassessed, with R1v confirmed in 74 patients (75%), Rx in 16%, and R0 in 9%. Presence/absence of residual neoplasia could be assessed in 66/74 patients during endoscopic reassessment (52) and/or in the surgical resection specimen (14), and 33/66 (50%) had residual neoplasia. Residual neoplasia detected during endoscopy was always endoscopically visible and biopsies from a normal-appearing ER scar did not detect additional neoplasia. Of 25 patients who underwent endoscopic follow-up (median 37 months [interquartile range 12-50]), 4 developed local recurrence (16.0%), all detected as visible abnormalities. CONCLUSIONS: After ER with R1v, 50% of patients had no residual neoplasia. Histological evaluation of ER margins appears challenging, as in this study 75% of documented R1v cases were confirmed during reassessment. Endoscopic reassessment 8-12 weeks after ER seems to accurately detect residual neoplasia and can help to determine the most appropriate strategy for patients with R1v.

Endoscopic submucosal dissection for early esophageal squamous cell carcinoma: long-term results from a Western cohort.

BACKGROUND: Although endoscopic submucosal dissection (ESD) is established as first-choice treatment for early esophageal squamous cell carcinoma (ESCC) worldwide, most data are derived from Asian studies. We aimed to evaluate the long-term outcomes of ESD for patients with early ESCC in a Western cohort. METHODS: In this retrospective cohort study, patients with early ESCC amenable to ESD were included from four tertiary referral hospitals in the Netherlands between 2012 and 2017. All ESD procedures were performed by experienced endoscopists, after which the decision for additional treatment was made on a per-patient basis. Outcomes were curative resection rate, ESCC-specific survival, and overall survival. RESULTS: Of 68 included patients (mean age 69 years; 34 males), ESD was technically successful in 66 (97%; 95%CI 93%-100%), with curative resection achieved in 34/66 (52%; 95%CI 39%-64%). Among patients with noncurative resection, 15/32 (47%) underwent additional treatment, mainly esophagectomy (n = 10) or definitive chemoradiation therapy (n = 4). Endoscopic surveillance was preferred in 17/32 patients (53%), based on severe comorbidities or patient choice. Overall, 31/66 patients (47%) died during a median follow-up of 66 months; 8/31 (26%) were ESCC-related deaths. The 5-year overall and ESCC-specific survival probabilities were 62% (95%CI 52%-75%) and 86% (95%CI 77%-96%), respectively. CONCLUSION: In this Western cohort with long-term follow-up, the effectiveness and safety of ESD for early ESCC was confirmed, although the rate of noncurative resections was substantial. Irrespective of curative status, the long-term prognosis of these patients was limited mainly due to competing mortality.

No Evidence for an Association of HIV and Antiviral Treatment With Changes in Framingham Cardiovascular Risk Score in the Ndlovu Cohort Study.

BACKGROUND: HIV and antiretroviral therapy (ART) have been associated with increased cardiovascular disease (CVD) risk in high-income countries. The authors studied the longitudinal association between HIV and ART and nonlaboratory Framingham Risk Score (FRS) in a middle-income country. METHODS AND RESULTS: This longitudinal analysis of the NCS (Ndlovu Cohort Study), South Africa used baseline to 36-month follow-up data. Demographics, HIV, ART status, and cardiometabolic measures were obtained. FRS was used as a CVD risk measure. Through linear mixed models, FRS trends over time and the association with HIV were studied. Analysis included 1136 participants, with 609 (54%) having HIV, and 495 (81%) taking ART. At baseline, 9.8% of participants had a high FRS. People living with HIV (PLHIV) had a 3.2% lower FRS than HIV-negative participants (P<0.001). FRS increased similarly for both groups over time. Other factors associated with FRS were secondary and higher education (ß value: -0.075, P<0.001; ß value: -0.084, P<0.001) and alcohol consumption (ß value: 0.011, P<0.001). CONCLUSIONS: CVD risk increased for all participants over 36 months, suggesting classic risk factors rather than HIV status or ART to be drivers of CVD risk. People living with HIV had a significantly lower FRS than their HIV-negative counterparts, possibly related to HIV itself or a more frequent interaction with healthcare services. No association of HIV and ART with changes in FRS over 36 months was observed, suggesting the need for research using clinical endpoints to elucidate the effects of HIV and ART on CVD risk. Population-based prevention of CVD risk factors in sub-Saharan Africa is warranted, regardless of HIV status.

Western outcomes of circumferential endoscopic submucosal dissection for early esophageal squamous cell carcinoma.

BACKGROUND AND AIMS: Circumferential endoscopic submucosal dissection (cESD) in the esophagus has been reported to be feasible in small Eastern case series. We assessed the outcomes of cESD in the treatment of early esophageal squamous cell carcinoma (ESCC) in Western countries. METHODS: We conducted an international study at 25 referral centers in Europe and Australia using prospective databases. We included all patients with ESCC treated with cESD before November 2022. Our main outcomes were curative resection according to European guidelines and adverse events. RESULTS: A total of 171 cESDs were performed on 165 patients. En bloc and R0 resections rates were 98.2% (95% confidence interval [CI], 95.0-99.4) and 69.6% (95% CI, 62.3-76.0), respectively. Curative resection was achieved in 49.1% (95% CI, 41.7-56.6) of the lesions. The most common reason for noncurative resection was deep submucosal invasion (21.6%). The risk of stricture requiring 6 or more dilations or additional techniques (incisional therapy/stent) was high (71%), despite the use of prophylactic measures in 93% of the procedures. The rates of intraprocedural perforation, delayed bleeding, and adverse cardiorespiratory events were 4.1%, 0.6%, and 4.7%, respectively. Two patients died (1.2%) of a cESD-related adverse event. Overall and disease-free survival rates at 2 years were 91% and 79%. CONCLUSIONS: In Western referral centers, cESD for ESCC is curative in approximately half of the lesions. It can be considered a feasible treatment in selected patients. Our results suggest the need to improve patient selection and to develop more effective therapies to prevent esophageal strictures.

EAES Multidisciplinary Rapid Guideline: systematic review, meta-analysis, GRADE assessment and evidence-informed recommendations on the surgical management of paraesophageal hernias.

BACKGROUND: New evidence has emerged since latest guidelines on the management of paraesophageal hernia, and guideline development methodology has evolved. Members of the European Association for Endoscopic Surgery have prioritized the management of paraesophageal hernia to be addressed by pertinent recommendations. OBJECTIVE: To develop evidence-informed clinical practice recommendations on paraesophageal hernias, through evidence synthesis and a structured evidence-to-decision framework by an interdisciplinary panel of stakeholders. METHODS: We performed three systematic reviews, and we summarized and appraised the certainty of the evidence using the GRADE methodology. A panel of general and upper gastrointestinal surgeons, gastroenterologists and a patient advocate discussed the evidence in the context of benefits and harms, the certainty of the evidence, acceptability, feasibility, equity, cost and use of resources, moderated by a Guidelines International Network-certified master guideline developer and chair. We developed the recommendations in a consensus meeting, followed by a modified Delphi survey. RESULTS: The panel suggests surgery over conservative management for asymptomatic/minimally symptomatic paraesophageal hernias (conditional recommendation), and recommends conservative management over surgery for asymptomatic/minimally symptomatic paraesophageal hernias in frail patients (strong recommendation). Further, the panel suggests mesh over sutures for hiatal closure in paraesophageal hernia repair, fundoplication over gastropexy in elective paraesophageal hernia repair, and gastropexy over fundoplication in patients who have cardiopulmonary instability and require emergency paraesophageal hernia repair (conditional recommendation). A strong recommendation means that the proposed course of action is appropriate for the vast majority of patients. A conditional recommendation means that most patients would opt for the proposed course of action, and joint decision-making of the surgeon and the patient is required. Accompanying evidence summaries and evidence-to-decision frameworks should be read when using the recommendations. This guideline applies to adult patients with moderate to large paraesophageal hernias type II to IV with at least 50% of the stomach herniated to the thoracic cavity. The full guideline with user-friendly decision aids is available in https://app.magicapp.org/#/guideline/j7q7Gn . CONCLUSION: An interdisciplinary panel provides recommendations on key topics on the management of paraesophageal hernias using highest methodological standards and following a transparent process. GUIDELINE REGISTRATION NUMBER: PREPARE-2023CN018.

Diagnosis and management of Barrett esophagus: European Society of Gastrointestinal Endoscopy (ESGE) Guideline.

MR1 : ESGE recommends the following standards for Barrett esophagus (BE) surveillance:- a minimum of 1-minute inspection time per cm of BE length during a surveillance endoscopy- photodocumentation of landmarks, the BE segment including one picture per cm of BE length, and the esophagogastric junction in retroflexed position, and any visible lesions- use of the Prague and (for visible lesions) Paris classification- collection of biopsies from all visible abnormalities (if present), followed by random four-quadrant biopsies for every 2-cm BE length.Strong recommendation, weak quality of evidence. MR2: ESGE suggests varying surveillance intervals for different BE lengths. For BE with a maximum extent of ≥ 1 cm and < 3 cm, BE surveillance should be repeated every 5 years. For BE with a maximum extent of ≥ 3 cm and < 10 cm, the interval for endoscopic surveillance should be 3 years. Patients with BE with a maximum extent of ≥ 10 cm should be referred to a BE expert center for surveillance endoscopies. For patients with an irregular Z-line/columnar-lined esophagus of < 1 cm, no routine biopsies or endoscopic surveillance are advised.Weak recommendation, low quality of evidence. MR3: ESGE suggests that, if a patient has reached 75 years of age at the time of the last surveillance endoscopy and/or the patient's life expectancy is less than 5 years, the discontinuation of further surveillance endoscopies can be considered. Weak recommendation, very low quality of evidence. MR4: ESGE recommends offering endoscopic eradication therapy using ablation to patients with BE and low grade dysplasia (LGD) on at least two separate endoscopies, both confirmed by a second experienced pathologist.Strong recommendation, high level of evidence. MR5: ESGE recommends endoscopic ablation treatment for BE with confirmed high grade dysplasia (HGD) without visible lesions, to prevent progression to invasive cancer.Strong recommendation, high level of evidence. MR6: ESGE recommends offering complete eradication of all remaining Barrett epithelium by ablation after endoscopic resection of visible abnormalities containing any degree of dysplasia or esophageal adenocarcinoma (EAC).Strong recommendation, moderate quality of evidence. MR7: ESGE recommends endoscopic resection as curative treatment for T1a Barrett's cancer with well/moderate differentiation and no signs of lymphovascular invasion.Strong recommendation, high level of evidence. MR8: ESGE suggests that low risk submucosal (T1b) EAC (i. e. submucosal invasion depth ≤ 500 µm AND no [lympho]vascular invasion AND no poor tumor differentiation) can be treated by endoscopic resection, provided that adequate follow-up with gastroscopy, endoscopic ultrasound (EUS), and computed tomography (CT)/positrion emission tomography-computed tomography (PET-CT) is performed in expert centers.Weak recommendation, low quality of evidence. MR9: ESGE suggests that submucosal (T1b) esophageal adenocarcinoma with deep submucosal invasion (tumor invasion > 500 µm into the submucosa), and/or (lympho)vascular invasion, and/or a poor tumor differentiation should be considered high risk. Complete staging and consideration of additional treatments (chemotherapy and/or radiotherapy and/or surgery) or strict endoscopic follow-up should be undertaken on an individual basis in a multidisciplinary discussion.Strong recommendation, low quality of evidence. MR10 A: ESGE recommends that the first endoscopic follow-up after successful endoscopic eradication therapy (EET) of BE is performed in an expert center.Strong recommendation, very low quality of evidence. B: ESGE recommends careful inspection of the neo-squamocolumnar junction and neo-squamous epithelium with high definition white-light endoscopy and virtual chromoendoscopy during post-EET surveillance, to detect recurrent dysplasia.Strong recommendation, very low level of evidence. C: ESGE recommends against routine four-quadrant biopsies of neo-squamous epithelium after successful EET of BE.Strong recommendation, low level of evidence. D: ESGE suggests, after successful EET, obtaining four-quadrant random biopsies just distal to a normal-appearing neo-squamocolumnar junction to detect dysplasia in the absence of visible lesions.Weak recommendation, low level of evidence. E: ESGE recommends targeted biopsies are obtained where there is a suspicion of recurrent BE in the tubular esophagus, or where there are visible lesions suspicious for dysplasia.Strong recommendation, very low level of evidence. MR11: After successful EET, ESGE recommends the following surveillance intervals:- For patients with a baseline diagnosis of HGD or EAC:at 1, 2, 3, 4, 5, 7, and 10 years after last treatment, after which surveillance may be stopped.- For patients with a baseline diagnosis of LGD:at 1, 3, and 5 years after last treatment, after which surveillance may be stopped.Strong recommendation, low quality of evidence.

The Tissue Systems Pathology Test Outperforms Pathology Review in Risk Stratifying Patients With Low-Grade Dysplasia.

BACKGROUND & AIMS: Low-grade dysplasia (LGD) is associated with an increased risk of progression in Barrett's esophagus (BE); however, the diagnosis of LGD is limited by substantial interobserver variability. Multiple studies have shown that an objective tissue systems pathology test (TissueCypher Barrett's Esophagus Test, TSP-9), can effectively predict neoplastic progression in patients with BE. This study aimed to compare the risk stratification performance of the TSP-9 test vs benchmarks of generalist and expert pathology. METHODS: A blinded cohort study was conducted in the screening cohort of a randomized controlled trial of patients with BE with community-based LGD. Biopsies from the first endoscopy with LGD were assessed by the TSP-9 test and independently reviewed by 30 pathologists from 5 countries per standard practice. The accuracy of the test and the diagnoses in predicting high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) were compared. RESULTS: A total of 154 patients with BE (122 men), mean age 60.9 ± 9.8 years were studied. Twenty-four patients progressed to HGD/EAC within 5 years (median time of 1.7 years) and 130 did not progress to HGD/EAC within 5 years (median 7.8 years follow-up). The TSP-9 test demonstrated higher sensitivity (71% vs mean 63%, range 33%-88% across 30 pathologists), than the pathology review in detecting patients who progressed (P = .01186). CONCLUSIONS: The TSP-9 test outperformed the pathologists in risk stratifying patients with BE with LGD. Care guided by the test can provide an effective solution to variable pathology review of LGD, improving health outcomes by upstaging care to therapeutic intervention for patients at high risk for progression, while reducing unnecessary interventions in low-risk patients.

Diagnosis and management of barrett esophagus: european society of gastrointestinal endoscopy (ESGE) guideline

This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). It is an update of the previous (2017) Position Statement on the endoscopic management of Barrett esophagus.

Tracking Treatment Response in Cardiac Light-Chain Amyloidosis With Native T1 Mapping.

Importance: Cardiac magnetic resonance (CMR) imaging-derived extracellular volume (ECV) mapping, generated from precontrast and postcontrast T1, accurately determines treatment response in cardiac light-chain amyloidosis. Native T1 mapping, which can be derived without the need for contrast, has demonstrated accuracy in diagnosis and prognostication, but it is unclear whether serial native T1 measurements could also track the cardiac treatment response. Objective: To assess whether native T1 mapping can measure the cardiac treatment response and the association between changes in native T1 and prognosis. Design, Setting, and Participants: This single-center cohort study evaluated patients diagnosed with cardiac light-chain amyloidosis (January 2016 to December 2020) who underwent CMR scans at diagnosis and a repeat scan following chemotherapy. Analysis took place between January 2016 and October 2022. Main Outcomes and Measures: Comparison of biomarkers and cardiac imaging parameters between patients with a reduced, stable, or increased native T1 and association between changes in native T1 and mortality. Results: The study comprised 221 patients (mean [SD] age, 64.7 [10.6] years; 130 male [59%]). At 6 months, 183 patients (mean [SD] age, 64.8 [10.5] years; 110 male [60%]) underwent repeat CMR imaging. Reduced native T1 of 50 milliseconds or more occurred in 8 patients (4%), all of whom had a good hematological response; by contrast, an increased native T1 of 50 milliseconds or more occurred in 42 patients (23%), most of whom had a poor hematological response (27 [68%]). At 12 months, 160 patients (mean [SD] age, 63.8 [11.1] years; 94 male [59%]) had a repeat CMR scan. A reduced native T1 occurred in 24 patients (15%), all of whom had a good hematological response, and was associated with a reduction in N-terminal pro-brain natriuretic peptide (median [IQR], 2638 [913-5767] vs 423 [128-1777] ng/L; P < .001), maximal wall thickness (mean [SD], 14.8 [3.6] vs 13.6 [3.9] mm; P = .009), and E/e' (mean [SD], 14.9 [6.8] vs 12.0 [4.0]; P = .007), improved longitudinal strain (mean [SD], -14.8% [4.0%] vs -16.7% [4.0%]; P = .004), and reduction in both myocardial T2 (mean [SD], 52.3 [2.9] vs 49.4 [2.0] milliseconds; P < .001) and ECV (mean [SD], 0.47 [0.07] vs 0.42 [0.08]; P < .001). At 12 months, an increased native T1 occurred in 24 patients (15%), most of whom had a poor hematological response (17 [71%]), and was associated with an increased N-terminal pro-brain natriuretic peptide (median [IQR], 1622 [554-5487] vs 3150 [1161-8745] ng/L; P = .007), reduced left ventricular ejection fraction (mean [SD], 65.8% [11.4%] vs 61.5% [12.4%]; P = .009), and an increase in both myocardial T2 (mean [SD], 52.5 [2.7] vs 55.3 [4.2] milliseconds; P < .001) and ECV (mean [SD], 0.48 [0.09] vs 0.56 [0.09]; P < .001). Change in myocardial native T1 at 6 months was independently associated with mortality (hazard ratio, 2.41 [95% CI, 1.36-4.27]; P = .003). Conclusions and Relevance: Changes in native T1 in response to treatment, reflecting a composite of changes in T2 and ECV, are associated with in changes in traditional markers of cardiac response and associated with mortality. However, as a single-center study, these results require external validation in a larger cohort.

An Automated Tissue Systems Pathology Test Can Standardize the Management and Improve Health Outcomes for Patients With Barrett's Esophagus.

INTRODUCTION: Low-grade dysplasia (LGD) in Barrett's esophagus (BE) is associated with an increased risk of progression to high-grade dysplasia or esophageal adenocarcinoma. However, because of substantial interobserver variability in the diagnosis of LGD, a patient's management plan and health outcome depend largely on which pathologist reviews their case. This study evaluated the ability of a tissue systems pathology test that objectively risk stratifies patients with BE (TissueCypher, TSP-9) to standardize management in a manner consistent with improved health outcomes for patients with BE. METHODS: A total of 154 patients with BE with community-based LGD from the prospectively followed screening cohort of the SURF trial were studied. Management decisions were simulated 500 times with varying generalist (n = 16) and expert (n = 14) pathology reviewers to determine the most likely care plan with or without use of the TSP-9 test for guidance. The percentage of patients receiving appropriate management based on the known progression/nonprogression outcomes was calculated. RESULTS: The percentage of patients with 100% of simulations resulting in appropriate management significantly increased from 9.1% for pathology alone, to 58.4% when TSP-9 results were used with pathology, and further increased to 77.3% of patients receiving appropriate management when only TSP-9 results were used. Use of the test results also significantly increased the consistency of management decisions for patients when their slides were reviewed by different pathologists ( P < 0.0001). DISCUSSION: Management guided by the TSP-9 test can standardize care plans by increasing the early detection of progressors who can receive therapeutic interventions, while also increasing the percentage of nonprogressors who can avoid unnecessary therapy and be managed by surveillance alone.