Lactate Suppresses Growth of Esophageal Adenocarcinoma Patient-Derived Organoids through Alterations in Tumor NADH/NAD+ Redox State.

Barrett's esophagus (BE) is a common precancerous lesion that can progress to esophageal adenocarcinoma (EAC). There are significant alterations in the esophageal microbiome in the progression from healthy esophagus to BE to EAC, including an increased abundance of a variety of lactate-producing bacteria and an increase of lactate in the tumor microenvironment, as predicted by metabolic modeling. The role of bacterial lactate in EAC is unknown.

Modeling Epithelial Homeostasis and Perturbation in Three-Dimensional Human Esophageal Organoids.

Esophageal organoids from a variety of pathologies including cancer are grown in Advanced Dulbecco's Modified Eagle Medium-Nutrient Mixture F12 (hereafter ADF). However, the currently available ADF-based formulations are suboptimal for normal human esophageal organoids, limiting the ability to compare normal esophageal organoids with those representing a given disease state. We have utilized immortalized normal human esophageal epithelial cell (keratinocyte) lines EPC1 and EPC2 and endoscopic normal esophageal biopsies to generate three-dimensional (3D) organoids.

AMPK Activation Serves as a Common Pro-Survival Pathway in Esophageal Adenocarcinoma Cells.

Esophageal adenocarcinoma (EAC) is a subtype of esophageal cancer that is difficult to treat, with overall poor survival and frequent recurrence despite curative-intent treatment strategies. There is limited understanding of EAC resistance mechanisms to chemotherapy or radiation. We have found that the AMP-activated protein kinase (AMPK) can serve a pro-survival function in EAC cells in response to cytotoxic treatments.

Drug Delivery Opportunities in Esophageal Cancer: Current Treatments and Future Prospects.

With one of the highest mortality rates of all malignancies, the 5-year survival rate for esophageal cancer is under 20%. Depending on the stage and extent of the disease, the current standard of care treatment paradigm includes chemotherapy or chemoradiotherapy followed by surgical esophagogastrectomy, with consideration for adjuvant immunotherapy for residual disease. This regimen has high morbidity, due to anatomic changes inherent in surgery, the acuity of surgical complications, and off-target effects of systemic chemotherapy and immunotherapy.

Modeling epithelial homeostasis and perturbation in three-dimensional human esophageal organoids.

Background: Esophageal organoids from a variety of pathologies including cancer are grown in Advanced Dulbecco's Modified Eagle Medium-Nutrient Mixture F12 (hereafter ADF). However, the currently available ADF-based formulations are suboptimal for normal human esophageal organoids, limiting the ability to compare normal esophageal organoids with those representing a given disease state.

Methods: We have utilized immortalized normal human esophageal epithelial cell (keratinocyte) lines EPC1 and EPC2 and endoscopic normal esophageal biopsies to generate three-dimensional (3D) organoids.

Updates in Translational Science for Esophageal and Gastric Cancers.

In this article, the authors summarize the current state of translational science for esophageal and gastric cancers. The available targeted therapies, immunotherapies, and recently discovered molecular targets are reviewed. The authors introduce circulating tumor deoxyribonucleic acid and its promise as a biomarker to detect disease recurrence.

Microscopic Small Airway Abnormalities Identified in Early Idiopathic Pulmonary Fibrosis Using Endobronchial Optical Coherence Tomography.

Idiopathic pulmonary fibrosis (IPF) affects the subpleural lung but is considered to spare small airways. Micro-computed tomography (micro-CT) studies demonstrated small airway reduction in end-stage IPF explanted lungs, raising questions about small airway involvement in early-stage disease. Endobronchial optical coherence tomography (EB-OCT) is a volumetric imaging modality that detects microscopic features from subpleural to proximal airways.

A Pilot Study Using Machine Learning Algorithms and Wearable Technology for the Early Detection of Postoperative Complications After Cardiothoracic Surgery.

Objective: To evaluate whether a machine learning algorithm (i.e. the "NightSignal" algorithm) can be used for the detection of postoperative complications prior to symptom onset after cardiothoracic surgery.

Disrupting CD38-driven T cell dysfunction restores sensitivity to cancer immunotherapy.

A central problem in cancer immunotherapy with immune checkpoint blockade (ICB) is the development of resistance, which affects 50% of patients with metastatic melanoma. T cell exhaustion, resulting from chronic antigen exposure in the tumour microenvironment, is a major driver of ICB resistance. Here, we show that CD38, an ecto-enzyme involved in nicotinamide adenine dinucleotide (NAD) catabolism, is highly expressed in exhausted CD8 T cells in melanoma and is associated with ICB resistance.

Food Deserts Increase Readmission After Esophagectomy for Cancer: A Multi-institutional Study.

Background: Food deserts are low-income census tracts with poor access to supermarkets and are associated with worse outcomes in breast, colon, and a small number of esophageal cancer patients. This study investigated residency in food deserts on readmission rates in a multi-institutional cohort of esophageal cancer patients undergoing trimodality therapy.

Methods: A retrospective review of patients who underwent trimodality therapy at 6 high-volume institutions from January 2015 to July 2019 was performed.

Tumor-Derived CCL5 Recruits Cancer-Associated Fibroblasts and Promotes Tumor Cell Proliferation in Esophageal Squamous Cell Carcinoma.

Unlabelled: Cancer-associated fibroblasts (CAF) can promote tumor growth, metastasis, and therapeutic resistance in esophageal squamous cell carcinoma (ESCC), but the mechanisms of action remain elusive. Our objective was to identify secreted factor(s) that mediate the communication between CAFs and ESCC tumor cells with the aim of identifying potential druggable targets. Through unbiased cytokine arrays, we have identified CC motif chemokine ligand 5 (CCL5) as a secreted factor that is increased upon co-culture of ESCC cells and CAFs, which we replicated in esophageal adenocarcinoma (EAC) with CAFs.

Intraoperative fluorescence imaging in esophagectomy and its application to the robotic platform: a narrative review.

Background And Objective: Robotic-assisted esophagectomy is an approach to minimally invasive esophagectomy (MIE) that has demonstrated equivalent or improved outcomes relative to open and other minimally invasive techniques. The robotic approach also allows unique opportunities to improve complications following esophagectomy through use of enhanced visualization tools, including intraoperative fluorescence imaging. In this review, we summarize the specific uses of intraoperative fluorescence imaging as an adjunct tool during esophagectomy and discuss its application to the robotic platform.

Advances in Imaging to Aid Segmentectomy for Lung Cancer.

Pulmonary segmentectomy has become a widely accepted technique for resection of early-stage lung cancers. Intraoperative identification of small nodules within the lung parenchyma and definition of segmental anatomy are essential for oncologic segmental resection and significantly enhanced by recent advances in imaging techniques. Advances in imaging for nodule localization, using preoperative markers and three-dimensional computed tomography, delineation of segmental anatomy, and sentinel lymph node mapping have become important components of planning and performing minimally invasive anatomic segmentectomies and are particularly well suited for the evolving robotic-assisted platform.

Early vs Delayed Surgery for Esophageal Cancer During the COVID-19 Pandemic.

Background: During the coronavirus disease 2019 pandemic, national guidelines recommended that elective surgery for esophageal cancer be deferred by 3 months when hospital resources are limited. The impact of this delay on patient outcomes is unknown. We sought to evaluate the survival of patients with stage I and II/III esophageal cancer who undergo early vs delayed treatment.

Contributing factors to lymph node recovery with esophagectomy by thoracic surgeons: an analysis of the Society of Thoracic Surgeons General Thoracic Surgery Database.

Given the association between lymphadenectomy and survival after esophagectomy, and the ongoing development of effective adjuvant protocols for identified residual disease, we determined factors contributing to lymph node yield and effects on postoperative morbidity following esophagectomy by thoracic surgeons. Using the Society of Thoracic Surgeons General Thoracic Surgery Database, all patients who underwent esophagectomy for primary esophageal cancer with gastric conduit reconstruction from 2012 to 2016 were identified. Patient demographics, technical factors, and tumor characteristics associated with lymph node yield were determined using a multivariable multilevel mixed-effects regression model.

Patient-derived organoids as a platform for modeling a patient's response to chemoradiotherapy in esophageal cancer.

3D patient-derived organoids (PDOs) have been utilized to evaluate potential therapies for patients with different cancers. However, the use of PDOs created from treatment-naive patient biopsies for prediction of clinical outcomes in patients with esophageal cancer has not yet been reported. Herein we describe a pilot prospective observational study with the goal of determining whether esophageal cancer PDOs created from treatment naive patients can model or predict clinical outcomes.

Alcohol Metabolism Enriches Squamous Cell Carcinoma Cancer Stem Cells That Survive Oxidative Stress via Autophagy.

Background: Alcohol (ethanol) consumption is a major risk factor for head and neck and esophageal squamous cell carcinomas (SCCs). However, how ethanol (EtOH) affects SCC homeostasis is incompletely understood.

Methods: We utilized three-dimensional (3D) organoids and xenograft tumor transplantation models to investigate how EtOH exposure influences intratumoral SCC cell populations including putative cancer stem cells defined by high CD44 expression (CD44H cells).

Understanding the cellular origin and progression of esophageal cancer using esophageal organoids.

Three-dimensional (3D) organoids are a novel tool to model epithelial cell biology and human diseases of the esophagus. 3D organoid culture systems have been utilized to investigate the pathobiology of esophageal cancer, including both squamous cell carcinoma and adenocarcinoma. Additional organoid-based approaches for study of esophageal development and benign esophageal diseases have provided key insights into esophageal keratinocyte differentiation and mucosal regeneration.