Biologically-targeted discovery-replication scan identifies G×G interaction in relation to risk of Barrett's esophagus and esophageal adenocarcinoma.

Inherited genetics represents an important contributor to risk of esophageal adenocarcinoma (EAC), and its precursor Barrett's esophagus (BE). Genome-wide association studies have identified ∼30 susceptibility variants for BE/EAC, yet genetic interactions remain unexamined. To address challenges in large-scale G×G scans, we combined knowledge-guided filtering and machine learning approaches, focusing on genes with (A) known/plausible links to BE/EAC pathogenesis (n=493) or (B) prior evidence of biological interactions (n=4,196).

Morbidity and mortality in patients with stage IV pancreatic adenocarcinoma and acute cholangitis: Outcomes and risk prognostication.

Background: Acute cholangitis (AC) is a common complication of pancreatic ductal adenocarcinoma (PDAC). Herein, we evaluated outcomes after the first AC episode and predictors of mortality and AC recurrence in patients with stage IV PDAC.

Methods: We conducted a single-center, retrospective observational study using institutional databases.

Early-onset Colorectal Cancer Patients Do Not Require Shorter Intervals for Post-surgical Surveillance Colonoscopy.

Background & Aims: Early-onset colorectal cancer (EO-CRC), diagnosed before age 50, is rising in incidence worldwide. Although post-surgical colonoscopy surveillance strategies exist, appropriate intervals in EO-CRC remain elusive, as long-term surveillance outcomes remain scant. We sought to compare findings of surveillance colonoscopies of EO-CRC with patients with average onset colorectal cancer (AO-CRC) to help define surveillance outcomes in these groups.

Clinical and molecular characteristics of early-onset vs average-onset esophagogastric cancer.

Background: The rate of esophagogastric cancer is rising among individuals under 50 years of age. It remains unknown whether early-onset esophagogastric cancer represents a unique entity. This study investigated the clinical and molecular characteristics of early-onset and average-onset esophagogastric cancer .

Exocrine Pancreatic Insufficiency Induced by Immune Checkpoint Inhibitors.

Background: Scant data describe exocrine pancreatic insufficiency (EPI) secondary to immune checkpoint inhibitor (ICI) use. The goal of this study is to describe the incidence, risk factors, and clinical characteristics of patients with ICI-related EPI.

Patients And Methods: A single center, retrospective case-control study was performed of all ICI-treated patients at Memorial Sloan Kettering Cancer Center between January 2011 and July 2020.

A Prospective Clinical Trial to Evaluate Mesothelin as a Biomarker for the Clinical Management of Patients With Esophageal Adenocarcinoma.

Objective: To investigate the utility of serum soluble mesothelin-related peptide (SMRP) and tumor mesothelin expression in the management of esophageal adenocarcinoma (ADC).

Background: Clinical management of esophageal ADC is limited by a lack of accurate evaluation of tumor burden, treatment response, and disease recurrence. Our retrospective data showed that tumor mesothelin and its serum correlate, SMRP, are overexpressed and associated with poor outcomes in patients with esophageal ADC.

Layer thickness characterization of Faraday cup fast ion loss detectors.

Faraday cup fast ion loss detectors have attractive properties for fusion applications, as they can measure wide ranges of energy, are intrinsically neutron-hardened, and can be packaged in very small form factors. The latter allows them to be installed as arrays, offering opportunities to decouple fast ion loss location and magnitude in fully three-dimensional magnetic fields. In this work, we characterize the layer thicknesses of detector prototypes using spectral reflectance measurements, confocal laser scanning microscopy, as well as raster electron microscopy with a focused ion beam.

Esophageal and Esophagogastric Junction Cancers, Version 2.2023, NCCN Clinical Practice Guidelines in Oncology.

Cancers originating in the esophagus or esophagogastric junction constitute a major global health problem. Esophageal cancers are histologically classified as squamous cell carcinoma (SCC) or adenocarcinoma, which differ in their etiology, pathology, tumor location, therapeutics, and prognosis. In contrast to esophageal adenocarcinoma, which usually affects the lower esophagus, esophageal SCC is more likely to localize at or higher than the tracheal bifurcation.

Principles of phosphoproteomics and applications in cancer research.

Phosphorylation constitutes the most common and best-studied regulatory post-translational modification in biological systems and archetypal signalling pathways driven by protein and lipid kinases are disrupted in essentially all cancer types. Thus, the study of the phosphoproteome stands to provide unique biological information on signalling pathway activity and on kinase network circuitry that is not captured by genetic or transcriptomic technologies. Here, we discuss the methods and tools used in phosphoproteomics and highlight how this technique has been used, and can be used in the future, for cancer research.

Endoscopic stenting for malignant biliary obstruction is technically successful in patients with preexisting duodenal stents.

There are limited data on the success of endoscopic retrograde cholangiopancreatography (ERCP) in patients with malignant biliary and duodenal obstruction with a preexisting duodenal stent. The aim of this study was to evaluate patient and procedural outcomes of a cohort of patients with preexisting duodenal stents who underwent an attempt at ERCP for malignant biliary obstruction (MBO). This was a single-center retrospective study on consecutive patients with a preexisting duodenal stent who underwent attempted ERCP for MBO.

Gastric Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology.

Gastric cancer is the third leading cause of cancer-related deaths worldwide. Over 95% of gastric cancers are adenocarcinomas, which are typically classified based on anatomic location and histologic type. Gastric cancer generally carries a poor prognosis because it is often diagnosed at an advanced stage.

Implementation of Clinical Phosphoproteomics and Proteomics for Personalized Medicine.

The identification of biomarkers for companion diagnostics is revolutionizing the development of treatments tailored to individual patients in different disease areas including cancer. Precision medicine is most frequently based on the detection of genomic markers that correlate with the efficacy of selected targeted therapies. However, since nongenetic mechanisms also contribute to disease biology, there is a considerable interest of using proteomic techniques as additional source of biomarkers to personalize therapies.

Effectiveness of a surveillance program of upper endoscopy for upper gastrointestinal cancers in Lynch syndrome patients.

Background And Aims: Lynch syndrome (LS) is the most common cause of hereditary colorectal cancer and is associated with an increased lifetime risk of gastric and duodenal cancers of 8-16% and 7%, respectively; therefore, we aim to describe an esophagogastroduodenoscopy (EGD) surveillance program for upper gastrointestinal (GI) precursor lesions and cancer in LS patients.

Methods: Patients who either had positive genetic testing or met clinical criteria for LS who had a surveillance EGD at our institution from 1996 to 2017 were identified. Patients were included if they had at least two EGDs or an upper GI cancer detected on the first surveillance EGD.

Lidocaine for postoperative pain after cardiac surgery: a systematic review.

Objective: Lidocaine is one of the most widely used local anesthetics with well-known pharmacological properties. The purpose of this systematic review is to investigate the effects of lidocaine on postoperative pain scores and recovery after cardiac surgery.

Methods: A comprehensive database search was conducted by a reference librarian for randomized clinical trials (RCT) from January 1, 1980 to September 1, 2019.

Drug ranking using machine learning systematically predicts the efficacy of anti-cancer drugs.

Artificial intelligence and machine learning (ML) promise to transform cancer therapies by accurately predicting the most appropriate therapies to treat individual patients. Here, we present an approach, named Drug Ranking Using ML (DRUML), which uses omics data to produce ordered lists of >400 drugs based on their anti-proliferative efficacy in cancer cells. To reduce noise and increase predictive robustness, instead of individual features, DRUML uses internally normalized distance metrics of drug response as features for ML model generation.

Extended Duration Infusion of Hydroxocobalamin for Vasoplegic Rescue in Septic Shock.

Nitric oxide (NO) is a gaseous signaling molecule and a key endogenous mediator of vascular tone. Hydroxocobalamin (HCB) affects NO-mediated vasoplegia as (1) a direct inhibitor of nitric oxide synthase (NOS), thereby decreasing its production, and (2) by binding directly to NO and acting as a scavenger. HCB has been increasingly used in the treatment of refractory vasoplegia, particularly in cardiac surgery and liver transplant patients.

Defining low-risk lesions in early-stage esophageal adenocarcinoma.

Objective: As endoscopic approaches become more widely used to treat early-stage esophageal cancer, reliably identifying patients with less-aggressive tumors is paramount. We sought to identify risk factors for recurrence in patients with completely resected T1 esophageal adenocarcinoma.

Methods: We retrospectively analyzed a single-institutional database for all patients with completely resected pathologic T1 esophageal adenocarcinoma (1996-2016).

Indications for Total Gastrectomy in CDH1 Mutation Carriers and Outcomes of Risk-Reducing Minimally Invasive and Open Gastrectomies.

Importance: CDH1 variants are increasingly identified on commercially available multigene panel tests, calling for data to inform counseling of individuals without a family history of gastric cancer.

Objectives: To assess association between CDH1 variant pathogenicity or family history of gastric or lobular breast cancer and identification of signet ring cell cancer and to describe outcomes of risk-reducing minimally invasive and open total gastrectomy.

Design, Setting, And Participants: This cohort study was performed from January 1, 2006, to January 1, 2020, in 181 patients with CDH1 germline variants from a single institution.

Bevacizumab does not increase risk of perforation in patients undergoing percutaneous endoscopic gastrostomy or jejunostomy placement.

Introduction: Bevacizumab is a humanized anti-vascular endothelial growth factor monoclonal antibody used in the treatment of cervical cancer, ovarian cancer, colorectal cancer, lung cancer, renal cell cancer, and recurrent glioblastomas. Its approval by US FDA was issued with a black box warning that its use has been associated with a risk of gastrointestinal (GI) tract perforation and that it should be discontinued in patients who have experienced such. The reported incidence of GI perforation in those receiving bevacizumab is as high as 3%.

Developing a novel biofiltration treatment system by coupling high-rate infiltration trench technology with a plug-flow porous-media bioreactor.

The sequence of two infiltration steps combined with an intermediate aeration named 'sequential managed aquifer recharge technology (SMART)' proved to be a promising approach to replenish groundwater using treated wastewater effluents or impaired surface waters due to efficient inactivation of pathogens and improved removal of many trace organic chemicals. To minimize the physical footprint of such systems and overcome limitations through site-specific heterogeneity at conventional MAR sites, an engineered approach was taken to further advance the SMART concept. This study investigated the establishment of plug-flow conditions in a pilot scale subsurface bioreactor by providing highly controlled hydraulic conditions.

Differing Thresholds for Overriding Parental Refusals of Life-Sustaining Treatment.

When should doctors seek protective custody to override a parent's refusal of potentially lifesaving treatment for their child? The answer to this question seemingly has different answers for different subspecialties of pediatrics. This paper specifically looks at different thresholds for physicians overriding parental refusals of life-sustaining treatment between neonatology, cardiology, and oncology. The threshold for mandating treatment of premature babies seems to be a survival rate of 25-50%.

Esophageal and Esophagogastric Junction Cancers, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology.

Esophageal cancer is the sixth leading cause of cancer-related deaths worldwide. Squamous cell carcinoma is the most common histology in Eastern Europe and Asia, and adenocarcinoma is most common in North America and Western Europe. Surgery is a major component of treatment of locally advanced resectable esophageal and esophagogastric junction (EGJ) cancer, and randomized trials have shown that the addition of preoperative chemoradiation or perioperative chemotherapy to surgery significantly improves survival.