Citations

INTRODUCTION: Esophageal adenocarcinoma (EAC) is an aggressive cancer with poor prognosis. Barrett's esophagus (BE) is a critical precursor of EAC. Patients with BE undergo endoscopic surveillance to monitor disease progression although only a small fraction develop EAC. These procedures are invasive and have limited accuracy in predicting BE progression. We evaluated the utility of an 8-protein mass spectrometry panel in predicting progression in patients with BE. METHODS: Eighty untreated controls and 20 cases were selected from our institutional tissue registry. Quantitative mass-spectrometry was performed on microdissected tissue sections. Data were split into 80% training and 20% test sets. We used Least Absolute Shrinkage and Selection Operator-regularized regression to train a logistic classifier on training data. Classifier performance was evaluated in test data. RESULTS: Ninety-two samples had sufficient tissue for mass spectrometry analysis (18 progressors, 74 nonprogressors). The multivariable regression model produced a sensitivity of 100% and a specificity of 39% in the overall cohort, with AUCs of 0.75 and 0.89 in the overall and test cohorts, respectively. Cox proportional hazards time-to-progression (TTP) showed a hazard ratio of 66.1 (95% CI 7.79–561, P = 0.00012) for the model prediction. DISCUSSION: The promising performance of the model generated here suggests that the test may aid in selecting patients most likely to benefit from active BE surveillance. Moreover, the association of this model's prediction with time-to-progression may offer decision support for management of patients likely to progress quickly. These results support continued development of this proteomic panel as a risk stratification tool for patients with BE.

Goals: A systematic review and meta-analysis of published clinical validity studies was conducted to evaluate the predictive performance of the TSP-9 test. Background: Identifying patients with Barrett’s esophagus (BE) who will progress to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) is challenging. The tissue systems pathology (TSP-9) test can predict risk of progression to HGD/EAC in BE patients. Study: Databases were searched for studies that assessed the clinical validity of TSP-9, and data describing progressors, non-progressors, TSP-9 results, and hazard ratios (HR) with 95% confidence intervals (CIs) were extracted. Odds ratios (OR), sensitivity, specificity, and prevalence-adjusted positive and negative predictive values (PPV adj /NPV adj ) were calculated and used for meta-analysis. Results: Six studies met eligibility criteria, comprising 699 patients. ORs and HRs for TSP-9 had mean common effect size estimates of 6.52 (95% CI: 4.40-9.66, P <0.0001, I 2 =33%) and 6.66 (95% CI: 4.59-9.66, P <0.0001, I 2 =0%), respectively, for predicting progression to HGD/EAC. Mean common effect size estimates were 61% (95% CI: 54%-68%) for sensitivity, 81% (95% CI: 78%-84%) for specificity, 28% (95% CI: 17%-42%) for PPV adj (high risk), 14% (95% CI: 9%-21%) for PPV adj (high/int risk), and 97% (95% CI: 96%-98%) for NPV adj with minimal inter-study heterogeneity ( I 2 =79%, 21%, 0%, 0%, and 0%, respectively). Conclusions: Effect estimates of TSP-9 performance demonstrate that the test provides risk stratification for BE patients. The TSP-9 test can provide clinically impactful results to enable escalation of care for high-risk patients or to identify low-risk patients who can be safely managed with routine surveillance.

Goals: This study aimed to assess perspectives and practices among expert gastroenterologists regarding the screening, diagnosis, and management of BE. Background: Significant variability in the management of Barrett’s esophagus (BE) persists among physicians despite the development and dissemination of several clinical practice guidelines. Study: An online survey was conducted with 38 expert gastroenterologists specializing in BE management. The 38-question survey evaluated demographics, medical management, and attitudes toward endoscopic treatment, with responses analyzed for trends and variations. Results: Of the 38 experts, 34 (89%) responded. Respondents were primarily male (85%), with 82% affiliated with academic hospitals and 53% clinically focused on BE. Half discussed BE risks during initial consultations for gastroesophageal reflux disease (GERD). Most (61.8%) agreed BE should be considered in women with chronic GERD, and 88.2% regularly used narrow-band imaging (NBI). However, 44% were neutral or disagreed with diagnosing BE based solely on community gastroenterologist biopsies, and acceptance of Wide-Area Transepithelial Sampling with 3D Analysis (WATS-3D) for Barrett’s esophagus diagnosis and surveillance was limited. Fifty-three percent recommended ablation for nondysplastic BE. Fifty-two percent recommended indefinite daily PPI therapy after complete eradication of intestinal metaplasia (CEIM), regardless of symptoms. When encountering cardia intestinal metaplasia after endoscopic eradication, 38% recommended ablation, while 47% continued surveillance. Conclusion: This study highlights substantial variations in the management of BE among expert gastroenterologists, despite the existence of updated guidelines. Identifying these discrepancies is crucial for optimizing care. Further efforts are needed to standardize practices and enhance the implementation of evidence-based guidelines in clinical settings.

Abstract Aberrant DNA methylation and copy-number alterations (CNA) drive Barrett’s esophagus progression to esophageal adenocarcinoma; however, their combined utility for early detection is unclear. We aimed to identify and validate methylated DNA markers (MDM) and CNAs to distinguish esophageal adenocarcinoma/high-grade dysplasia (HGD) from nondysplastic Barrett’s esophagus (NDBE). In this multiphase, multicenter study, we discovered and validated MDMs and quantified CNAs utilizing whole-genome methylation sequencing of esophageal brushings. DNA biomarkers identified from discovery were further validated in independent patients with paired esophageal brushing and swallowed capsule sponge samples. MDMs were filtered against a reduced representation bisulfite sequencing dataset obtained from independent tissue samples to advance only concordant candidates. CNA burden was quantified using ichorCNA-derived aneuploidy scores (AS). Two hundred MDMs discovered in HGD (N = 18) and esophageal adenocarcinoma (N = 18) versus NDBE brushing samples (N = 18) were tested in independent samples (N = 146). A 52-MDM panel achieved a cross-validated AUC of 0.88 [95% confidence interval (CI), 0.82–0.95]; the addition of AS improved discrimination of HGD/esophageal adenocarcinoma from NDBE to 0.91 (95% CI, 0.86–0.97) AUC. At 80% specificity, the combined model detected 93% of esophageal adenocarcinoma and 88% of HGD cases. In paired capsule sponge samples, a 58-MDM panel achieved a cross-validated AUC of 0.77 (95% CI, 0.66–0.88); a combined 58-MDM and AS model achieved AUC 0.80 (95% CI, 0.7–0.9). MDMs and AS discerned HGD/esophageal adenocarcinoma from normal esophagus/NDBE in endoscopic brushing and capsule sponge samples. This approach may improve Barrett’s esophagus surveillance. Prevention Relevance: This study demonstrates that combining epigenetic and genomic biomarkers across minimally invasive sampling methods can accurately distinguish HGD/esophageal adenocarcinoma from nondysplastic Barrett’s esophagus, offering promising, less invasive strategies to improve BE surveillance and enable endoscopic therapy for esophageal adenocarcinoma prevention and treatment.

406 Background: Anxiety is highly prevalent among oncology patients, often arising from uncertainty around diagnosis, treatment options, and prognosis. Elevated anxiety can impair decision-making, reduce treatment adherence, and diminish overall quality of life. Effective second opinion consultations may help mitigate anxiety and increase patients’ confidence in recommending healthcare services to others. Our study evaluates the impact of oncology second opinion (OSO) consultations on anxiety level (AL) and confidence in the organization (CIO) providing the second opinion, i.e., Cincinnati Cancer Advisors (CCA) and Naples Cancer Advisors (NCA). Methods: The study included patients with cancer diagnoses, age ≥18 years, who were served in person for OSO at CCA and NCA. A survey was used before and after consultation, measuring AL (scale 1- 10) and CIO level (scale 1 - 10), assessed by asking patients how likely they would refer loved ones to the organization. After the content and face validation, patients completed the survey anonymously, put it in a sealed envelope, and dropped it in a dedicated box. Data was analyzed using paired t-tests to compare the change from pre- to post-consultation scores. Spearman’s correlation test was used to assess the relation between the changes in AL and CIO. Statistical significance was assessed using an alpha-level of 0.05. Analyses were conducted via R and R Studio (version 2025.5.1.513). Results: Overall, 46 consecutive patients participated (45 completed AL pre and post visit survey and 43 completed the CIO pre and post visit survey). The mean pre-consultation anxiety score was 5.92 (SD = 2.58), and the post-consultation score was 3.87 (SD = 2.10), demonstrating a significant reduction (mean paired difference = -2.05; p < 0.0001). The mean pre-consult CIO was 8.21 (SD = 2.03), increasing to 9.73 post-consultation (SD = 0.53), indicating a significant improvement (mean paired difference = 1.66; p < 0.0001). The correlation between changes in AL and CIO was not statistically significant, which may be attributed to the high baseline CIO scores (ceiling effect) and the small sample size. Conclusions: Oncology second opinion was associated with a marked decrease in patient AL and a significant increase in CIO. The patient survey will continue to recruit additional participants to increase the sample size and explore the correlation between changes in AL and CIO. Studying the downstream impact on patient experience and outcome is warranted.

Importance Multiparametric magnetic resonance imaging (MRI), with or without prostate biopsy, has become the standard of care for diagnosing clinically significant prostate cancer. Resource capacity limits widespread adoption. Biparametric MRI, which omits the gadolinium contrast sequence, is a shorter and cheaper alternative offering time-saving capacity gains for health systems globally. Objective To assess whether biparametric MRI is noninferior to multiparametric MRI for diagnosis of clinically significant prostate cancer. Design, Setting, and Participants A prospective, multicenter, within-patient, noninferiority trial of biopsy-naive men from 22 centers (12 countries) with clinical suspicion of prostate cancer (elevated prostate-specific antigen [PSA] level and/or abnormal digital rectal examination findings) from April 2022 to September 2023, with the last follow-up conducted on December 3, 2024. Interventions Participants underwent multiparametric MRI, comprising T2-weighted, diffusion-weighted, and dynamic contrast–enhanced (DCE) sequences. Radiologists reported abbreviated biparametric MRI first (T2-weighted and diffusion-weighted), blinded to the DCE sequence. After unblinding, radiologists reported the full multiparametric MRI. Patients underwent a targeted biopsy with or without systematic biopsy if either biparametric MRI or multiparametric MRI was suggestive of clinically significant prostate cancer. Main outcomes and measures The primary outcome was the proportion of men with clinically significant prostate cancer. Secondary outcomes included the proportion of men with clinically insignificant cancer. The noninferiority margin was 5%. Results Of 555 men recruited, 490 were included for primary outcome analysis. Median age was 65 (IQR, 59-70) years and median PSA level was 5.6 (IQR, 4.4-8.0) ng/mL. The proportion of patients with abnormal digital rectal examination findings was 12.7%. Biparametric MRI was noninferior to multiparametric MRI, detecting clinically significant prostate cancer in 143 of 490 men (29.2%), compared with 145 of 490 men (29.6%) (difference, −0.4 [95% CI, −1.2 to 0.4] percentage points; P = .50). Biparametric MRI detected clinically insignificant cancer in 45 of 490 men (9.2%), compared with 47 of 490 men (9.6%) with the use of multiparametric MRI (difference, −0.4 [95% CI, −1.2 to 0.4] percentage points). Central quality control demonstrated that 99% of scans were of adequate diagnostic quality. Conclusion and relevance In men with suspected prostate cancer, provided image quality is adequate, an abbreviated biparametric MRI scan, with or without targeted biopsy, could become the new standard of care for prostate cancer diagnosis. With approximately 4 million prostate MRIs performed globally annually, adopting biparametric MRI could substantially increase scanner throughput and reduce costs worldwide. Trial registration ClinicalTrials.gov Identifier: NCT04571840

Abstract Background Post-traumatic headache (PTH) is a common acute and persistent symptom following mild traumatic brain injury (mTBI). Symptoms of cutaneous allodynia and presence of nociceptive sensitization might be associated with acute PTH and its persistence. The objectives of this study were to compare allodynia symptoms and cutaneous heat pain thresholds amongst males and females with acute PTH to healthy controls (HC) and determine if pain thresholds and allodynia symptoms are associated with PTH outcomes. Methods This prospective longitudinal study enrolled 139 adults with acute PTH attributed to mTBI as defined by the International Classification of Headache Disorders and 95 HC. All PTH participants completed a baseline research visit near PTH onset and a follow-up visit three to four months later. All PTH participants and a subset of HC completed the Allodynia Symptom Checklist (ASC-12) at each research visit. A different subset of the participants underwent quantitative sensory testing (QST) during baseline, 4-week, and 16-week research visits to quantify cutaneous heat pain thresholds at the forehead and forearms. Data from daily headache diaries were used to determine longitudinal PTH improvement versus non-improvement at three months. ASC-12 score and pain threshold comparisons were made between PTH and HC groups, PTH improved versus non-improved cohorts, and between PTH males and females. Results Participants with PTH had an average age of 42.6 years and 64.0% were female. HC had an average age of 40.0 years and 65.3% were female. At the first visit, PTH participant ASC-12 scores averaged 3.6 versus 0.1 amongst HC, p < 0.001. 44.8% of PTH participants had headache improvement at 3 months. ASC-12 scores were higher in the PTH non-improved versus improved group at baseline (4.0 versus 2.4, p = 0.038) and 3-month follow-up (3.4 versus 1.9, p = 0.012). ASC-12 scores were higher in females than males at baseline (4.7 versus 1.6, p < 0.001) and 3-months (3.9 versus 1.2, p < 0.001). Cutaneous heat pain thresholds at the forehead and forearm did not differ between any group. Conclusions PTH attributed to mTBI is associated with symptoms of cutaneous allodynia. Greater allodynia symptoms are present in females with PTH compared to males and may be associated with PTH non-improvement.

INTRODUCTION: The study aimed to develop consensus recommendations for the safe and appropriate use of liquid nitrogen spray cryotherapy in Barrett's esophagus and esophageal cancer. METHODS: Statements were initially formulated and grouped into categories of indications, training, preprocedure, intraprocedure, and postprocedure recommendations, frequency/timing of repeat procedures, and contraindications. Two investigators assessed the strength of the evidence for each statement using Grading of Recommendations Assessment, Development, and Evaluation methodology. Nineteen experts were invited to participate in a modified Delphi process. For statements that received >80% agreement, minor iterative edits were performed until there was unanimous consensus. If a threshold of 80% agreement was not reached, the statement was modified based on feedback and included in the next Delphi round. Statements were rejected if no consensus was reached after 3 rounds. RESULTS: After 3 Delphi rounds, 41 of 42 statements were accepted either in their original version (n = 11) or after modification based on expert input (n = 30). DISCUSSION: Through a modified Delphi process, we developed expert and evidence-based consensus recommendations to guide safe and appropriate use of liquid nitrogen spray cryotherapy in Barrett's esophagus and esophageal cancer.