Differential Infiltration of Key Immune T-Cell Populations Across Malignancies Varying by Immunogenic Potential and the Likelihood of Response to Immunotherapy.

Solid tumors vary by the immunogenic potential of the tumor microenvironment (TME) and the likelihood of response to immunotherapy. The emerging literature has identified key immune cell populations that significantly impact immune activation or suppression within the TME. This study investigated candidate T-cell populations and their differential infiltration within different tumor types as estimated from mRNA co-expression levels of the corresponding cellular markers.

Patient, facility, and surgical factors associated with significant delays to esophagectomy and subsequent poor outcomes: An analysis of 16,486 cases.

Objective: Delays to definitive surgery in esophageal cancer may be associated with disease progression and worsened survival. The objective of this study was to perform a national assessment for predictors of delay to esophagectomy and to assess for their impact on oncologic and survival outcomes.

Methods: The National Cancer Database, 2010 to 2020, was queried for patients with locally advanced esophageal adenocarcinoma (stage I-III).

More May Not Be Better: Comparison of Oncologic Outcomes Following Induction Chemotherapy Plus Chemoradiation and Chemoradiation Alone for Esophageal Adenocarcinoma.

Introduction: The oncologic benefit of induction chemotherapy (IC) before chemoradiation (CRT) compared to CRT alone for locally advanced esophageal and gastroesophageal junction (GEJ) adenocarcinoma is not well defined. We hypothesized that IC with CRT would improve survival and pathologic complete response rate compared to CRT alone.

Methods: A retrospective review of patients with biopsy proven esophageal or GEJ adenocarcinoma treated with preoperative CRT and IC + CRT and surgical resection from 2007 to 2023 at a single institution was performed.

Metastatic Melanoma to the Small Bowel and Colon: A Systematic Review of the Global Experience and Institutional Cohort Analysis Detailing a Rare Clinical Entity.

Introduction: Cutaneous melanoma is among the most common solid tumors to metastasize to the gastrointestinal (GI) tract. Literature summarizing the clinical experience and features of this unique pathology is lacking.

Methods: A systematic review of the available literature reporting clinically salient features of melanoma metastases to the small and large intestines was conducted.

DNA-PK inhibition enhances neoantigen diversity and increases T cell responses to immunoresistant tumors.

Effective antitumor T cell activity relies on the expression and MHC presentation of tumor neoantigens. Tumor cells can evade T cell detection by silencing the transcription of antigens or by altering MHC machinery, resulting in inadequate neoantigen-specific T cell activation. We identified the DNA-protein kinase inhibitor (DNA-PKi) NU7441 as a promising immunomodulator that reduced immunosuppressive proteins, while increasing MHC-I expression in a panel of human melanoma cell lines.

Survival Outcomes of Cytoreductive Surgery with HIPEC in Gastric Adenocarcinoma: A National Cancer Database Study.

Background: This study aimed to assess the impact of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) on the survival outcomes for patients with gastric cancer and peritoneal carcinomatosis (PC).

Methods: A retrospective analysis of the National Cancer Database from 2004 to 2020 identified patients with topography and histology codes consistent with gastric adenocarcinoma who underwent CRS/HIPEC. The exclusion criteria ruled out known other distant metastasis and missing key data.

Pathological Features Associated with Lymph Node Disease in Patients with Appendiceal Neuroendocrine Tumors.

This study aimed to evaluate the role of pathological features beyond tumor size in the risk of lymph node metastasis in appendiceal neuroendocrine tumors. Analyzing data from the national cancer database, we found that among 5353 cases, 18.8% had lymph node metastasis.

Multicellular immune ecotypes within solid tumors predict real-world therapeutic benefits with immune checkpoint inhibitors.

Background: Cancer initiation, progression, and immune evasion depend on the tumor microenvironment (TME). Thus, understanding the TME immune architecture is essential for understanding tumor metastasis and therapy response. This study aimed to create an immune cell states (CSs) atlas using bulk RNA-seq data enriched by eco-type analyses to resolve the complex immune architectures in the TME.

Gaining a new angle on pancreas cancer: A pre-operative thrombelastographic parameter predicts recurrence and survival among patients with resected periampullary and pancreatic adenocarcinoma.

Background: It has previously been demonstrated that Thrombelastography(TEG) angle may be associated with recurrence and survival in pancreas cancer in a cohort of patients operated on at the University of Colorado in 2016-2017. Now approaching 10 years of follow-up, we revisit these associations and strengthen these claims with multivariate analysis.

Methods: Retrospective chart review was performed.

The Tumor Microbiome as a Predictor of Outcomes in Patients with Metastatic Melanoma Treated with Immune Checkpoint Inhibitors.

Unlabelled: Emerging evidence supports the important role of the tumor microbiome in oncogenesis, cancer immune phenotype, cancer progression, and treatment outcomes in many malignancies. In this study, we investigated the metastatic melanoma tumor microbiome and its potential roles in association with clinical outcomes, such as survival, in patients with metastatic disease treated with immune checkpoint inhibitors (ICI). Baseline tumor samples were collected from 71 patients with metastatic melanoma before treatment with ICIs.

Generation and applications of x-ray and extreme ultraviolet beams carrying orbital angular momentum.

In addition to spin angular momentum, light can carry orbital angular momentum. The orbital angular momentum degree of freedom in the extreme ultraviolet and x-ray regimes enables fundamental studies of light-matter interactions and new methods to study materials. Advances in x-ray optics, as well as undulator radiation and high harmonic generation techniques, lead to the creation of beams with non-trivial phase structure, such as a helical phase structure, creating new possibilities for the use of extreme ultraviolet and x-ray photons with orbital angular momentum in probing complex electronic structures in matter.

Radiologic Occult Metastases in Pancreatic Cancer: Analysis of Risk Factors and Survival Outcomes in the Age of Contemporary Neoadjuvant Multi-agent Chemotherapy.

Background: Radiologic occult metastatic disease (ROMD) in patients with pancreatic ductal adenocarcinoma (PDAC) who undergo contemporary neoadjuvant chemotherapy (NAC) has not been well studied. This study sought to analyze the incidence, risk factors, and oncologic outcomes for patients who underwent the NAC approach for PDAC.

Methods: A retrospective review analyzed a prospectively maintained database of patients who had potentially resectable PDAC treated with NAC and were offered pancreatectomy at our institution from 2011 to 2022.

A regionally tailored epidemiological forecast and monitoring program to guide a healthcare system in the COVID-19 pandemic.

Background: During the COVID-19 pandemic, analytics and predictive models built on regional data provided timely, accurate monitoring of epidemiological behavior, informing critical planning and decision-making for health system leaders. At Atrium Health, a large, integrated healthcare system in the southeastern United States, a team of statisticians and physicians created a comprehensive forecast and monitoring program that leveraged an array of statistical methods.

Methods: The program utilized the following methodological approaches: (i) exploratory graphics, including time plots of epidemiological metrics with smoothers; (ii) infection prevalence forecasting using a Bayesian epidemiological model with time-varying infection rate; (iii) doubling and halving times computed using changepoints in local linear trend; (iv) death monitoring using combination forecasting with an ensemble of models; (v) effective reproduction number estimation with a Bayesian approach; (vi) COVID-19 patients hospital census monitored via time series models; and (vii) quantified forecast performance.

Effect of Neoadjuvant Chemotherapy on Tumor-Infiltrating Lymphocytes in Resectable Gastric Cancer: Analysis from a Western Academic Center.

Tumor-infiltrating lymphocytes (TILs) are an emerging biomarker predictive of response to immunotherapy across a spectrum of solid organ malignancies. The characterization of TILs in gastric cancer (GC) treated with contemporary, multiagent neoadjuvant chemotherapy (NAC) is understudied. In this retrospective investigation, we analyzed the degree of infiltration, phenotype, and spatial distribution of TILs via immunohistochemistry within resected GC specimens treated with or without NAC at a Western center.

Lean body mass index is a marker of advanced tumor features in patients with hepatocellular carcinoma.

Background: Obesity is an independent risk factor for the development of hepatocellular carcinoma (HCC) and may influence its outcomes. However, after diagnosis of HCC, like other malignancies, the obesity paradox may exist where higher body mass index (BMI) may in fact confer a survival benefit. This is frequently observed in patients with advanced HCC and cirrhosis, who often present late with advanced tumor features and cancer related weight loss.

MCL1 inhibition targets Myeloid Derived Suppressors Cells, promotes antitumor immunity and enhances the efficacy of immune checkpoint blockade.

Immune checkpoint inhibitors (ICIs) are now the first-line treatment for patients with advanced melanoma. Despite promising clinical results, many patients fail to respond to these therapies. BH3 mimetics, a novel class of small molecule inhibitors that bind and inhibit anti-apoptotic members of the BCL2 family proteins such as BCL2 or MCL1, have been very successful in treating hematologic malignancies.

The Effect of Laparoscopic Gastric Ischemic Preconditioning Prior to Esophagectomy on Anastomotic Stricture Rate and Comparison with Esophagectomy-Alone Controls.

Background: Benign anastomotic stricture is a recognized complication following esophagectomy. Laparoscopic gastric ischemic preconditioning (LGIP) prior to esophagectomy has been associated with decreased anastomotic leak rates; however, its effect on stricture and the need for subsequent endoscopic intervention is not well studied.

Methods: This was a case-control study at an academic medical center using consecutive patients undergoing oncologic esophagectomies (July 2012-July 2022).

Immune Landscape of Epstein-Barr Virus-Associated Gastric Cancer: Analysis From a Western Academic Institution.

Introduction: Epstein-Barr virus-associated gastric cancer (EBVaGC) may be a meaningful biomarker for potential benefit from immunotherapy. Further investigation is needed to characterize the immune landscape of EBVaGC. We assessed our institutional frequency of surgically treated EBVaGC and analyzed the immunologic biomarker profile and tumor-infiltrating lymphocyte (TIL) phenotypes of a series of EBVaGC compared to non-EBVaGC cases.