INTRODUCTION: We sought to develop a minimally invasive, robust, accessible nonendoscopic strategy to diagnose Barrett's esophagus (BE), esophageal adenocarcinoma (EAC), and its immediate precursor lesion, high-grade dysplasia (HGD) based on methylated DNA biomarkers applied to a retrievable sponge-capsule device in a cohort representative of the BE population (i.e., mostly short-segment, nondysplastic BE [NDBE]). METHODS: We identified 12 candidate methylation markers to distinguish normal vs abnormal esophagus. These 12 markers were first assayed in 21-paired matched NDBE-normal esophageal tissues, then assessed in a case-control study of 234 esophageal samples collected using a sponge-capsule device. A classification algorithm was developed using the least absolute shrinkage and selection operator in a 199-patient training set and tested in an independent 35-patient test set. RESULTS: Twelve markers (A1BG, C9orf50, cg00720137, FLI1, GRAMD1B, HOXB13, IRF4, KCNQ3, NTNG1, SPX, TBC1D30, and USP44) were significantly hypermethylated (i.e., all P < 0.05) in BE vs matched normal esophageal biopsies. A discriminatory 3-gene least absolute shrinkage and selection operator panel (USP44, TBC1D30, and NELL1), adjusted for age and sex, accurately distinguished HGD or EAC from normal control patients in both training (area under the receiver operating characteristic curve [AUC] 0.911, 95% confidence interval [CI] 0.863–0.959) and test (AUC 0.969, 95% CI 0.911–1.00) sets. In normal vs NDBE/LGD/HGD/EAC patients, this algorithm exhibited AUCs of 0.862 (95% CI 0.812–0.912) and 0.864 (95% CI 0.745–0.982) in training and test sets, respectively. In normal vs NDBE patients, the algorithm yielded AUCs of 0.819 (95% CI 0.748–0.889) and 0.776 (95% CI 0.583–0.968) in training and test sets, respectively. DISCUSSION: This discriminatory biomarker panel algorithm exemplifies a practical nonendoscopic strategy to diagnose BE, HGD, and EAC using a minimally invasive sponge-capsule device coupled with DNA methylation markers.

Background: Preclinical and clinical data indicate that chemoradiotherapy (CRT) in combination with checkpoint inhibitors may prime an anti-tumor immunological response in esophageal cancer. However, responses to neoadjuvant therapy can vary widely and the key biomarkers to determine response remain poorly understood. The fecal microbiome is a novel and potentially modifiable biomarker of immunotherapy response, and both fecal and tumor microbes have been found to associate with outcomes in esophageal cancer. Methods: Fecal and tumor samples were collected from patients with stage II–III resectable esophageal or gastroesophageal junction carcinoma treated with neoadjuvant immune checkpoint inhibitors (ICIs) plus CRT prior to surgical resection. Microbiome profiles were analyzed by 16S rRNA amplicon sequencing and taxonomic data were integrated with fecal metabolite analysis to assess microbial function. Results: The fecal microbiome of patients with pathological complete response (PCR) grouped in distinct clusters compared to patients with residual viable tumor (RVT) by Bray–Curtis diversity metric. Integrated taxonomic and metabolomic analysis of fecal samples identified a sphingolipid and primary bile acid as enriched in the PCR, the levels of which correlated with several bacterial species: Roseburis inulinivorans, Ruminococcus callidus, and Fusicantenibacter saccharivorans. Analysis of the tumor microbiome profiles identified several bacterial genera previously associated with esophageal tumors, including Streptococcus and Veillonella. Conclusions: These results further characterize the fecal and tumor microbiome of patients with operable esophageal cancer and identify specific microbes and metabolites that may help elucidate how microbes contribute to tumor response with neoadjuvant CRT combined with ICI.

Surgical Cardiac Sympathetic Denervation (CSD) has gained traction as a promising neuromodulatory therapy for Refractory Ventricular Tachyarrhythmias (RVT), particularly in patients with channelopathies and Ischemic (ICM) and Non-Ischemic Cardiomyopathies (NICM) who are refractory to conventional treatment. This mini review examines the pathophysiological role of the sympathetic nervous system in RVT and assesses the efficacy of Bilateral CSD (BCSD) through a literature review. Historical perspectives have traced the evolution of CSD from its initial use in intractable angina to its current application in ventricular arrhythmias. BCSD is associated with improved outcomes for refractory ventricular arrhythmias, with studies demonstrating approximately 60% reductions in implantable cardioverter defibrillator shocks and over 50% shock-and transplant-free survival at 1 year after BCSD. Notably, the 2017 AHA/ACC/HRS guidelines recommend Left CSD (LCSD) for certain etiologies of RVT, including congenital long QT syndrome, Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT), and VT/VF storm. Both Video-Assisted Thoracoscopic Surgery (VATS) and Robot-Assisted Thoracoscopic Surgery (RATS) BCSD are performed, with shorter operative times for RATS. Yet, most RVT CSD studies have a small sample size; therefore, complications may be underreported because the studies are underpowered. Although BCSD has superior reported outcomes with respect to left CSD, there may be confounding factors due to the selection of healthier patients for BCSD. Additional comparative effectiveness and cost-effectiveness data are needed to guide clinical practice. In conclusion, BCSD can restore the quality of life of severely impacted RVT patients; however, the benefits must be weighed against procedure-related risks, and further research should clarify the impact on long-term morbidity and mortality.

Introduction: Pulmonary arteriovenous malformations (PAVM) present with a variety of clinical manifestations, including hemoptysis. The usual management strategy relies upon interventional techniques, with surgery reserved for cases which are recalcitrant to less invasive measures. Case presentation: A 14-year-old female presented with massive and refractory hemoptysis. CTA and bronchoscopy did not identify a targetable lesion, but given her clinical instability she underwent percutaneous angiography which identified a right-sided PAVM with bronchial artery to pulmonary artery communication coursing near the right mainstem bronchus. Embolization procedures were initially successful to control bleeding, but recurrences of hemoptysis prompted surgical evaluation. Approximately two years after initial presentation, we performed robotic ligation of her PAVM which resulted in definitive control of the lesion with no additional bleeding episodes. She recovered well from surgery with a one-night hospital stay, and has experienced no surgical complications or recurrent bleeding to date. Conclusion: Rarely, pediatric PAVMs may require surgical intervention if interventional methods do not achieve definitive therapy. A variety of surgical techniques may be employed as dictated by the lesion's characteristics. Robotic approaches, including ligation, should be considered for patients with failure of conservative measures as it provides minimally invasive, precise technical management of PAVM.