Targeting Radiation Resistance in Oesophageal Adenocarcinoma with Pyrazinib-Functionalised Gold Nanoparticles.

Unlabelled: Only 20-30% of oesophageal adenocarcinoma (OAC) patients achieve a complete response to neoadjuvant chemo-radiotherapy for locally advanced tumours. Enhancing the response to radiation therapy is critical for improving outcomes in this aggressive cancer. Pyrazinib (P3) is a promising compound with radiosensitizing, anti-angiogenic, anti-inflammatory, and anti-metabolic properties.

Paraconduit hiatus hernia after esophageal cancer surgery: incidence, risk factors, and management.

In parallel with improved operative and oncologic outcomes for esophageal cancer, paraconduit hiatus hernia (PHH) is an increasingly recognized entity, both in the early postoperative phase and in long-term follow-up. The aim of this study was to assess the incidence of and risk factors for PHH, and to describe management approaches in a tertiary referral center. All patients undergoing surgery with curative intent for esophageal cancer from 2008 to 2022 at a single center were included.

Application of Machine Learning in a Rodent Malaria Model for Rapid, Accurate, and Consistent Parasite Counts.

Rodent malaria models serve as important preclinical antimalarial and vaccine testing tools. Evaluating treatment outcomes in these models often requires manually counting parasite-infected red blood cells (iRBCs), a time-consuming process, which can be inconsistent between individuals and laboratories. We have developed an easy-to-use machine learning (ML)-based software, Malaria Screener R, to expedite and standardize such studies by automating the counting of Plasmodium iRBCs in rodents.

Evidence for the Positive Impact of Centralization in Esophageal Cancer Surgery.

Objective: To analyze the impact of centralization on key metrics, outcomes, and patterns of care at the Irish National Center.

Background: Overall survival rates for esophageal cancer in the West have doubled in the last 25 years. An international trend towards centralization may be relevant; however, this model remains controversial, with Ireland centralizing esophageal cancer surgery in 2011.

Computed tomography (CT) derived radiomics to predict post-operative disease recurrence in gastric cancer; a systematic review and meta-analysis.

Introduction: Radiomics offers the potential to predict oncological outcomes from pre-operative imaging in order to identify 'high risk' patients at increased risk of recurrence. The application of radiomics in predicting disease recurrence provides tailoring of therapeutic strategies. We aim to comprehensively assess the existing literature regarding the current role of radiomics as a predictor of disease recurrence in gastric cancer.

Reducing recurrence rates in hiatal hernia repair: Results of a quality improvement study.

Background: Patient and procedure factors are considered in the decision-making process for surgical repair of hiatal hernias. Recurrence is multi-factorial and has been shown to be related to size, type, BMI and age.

Aims: This study examined recurrence rates in a single institution, identified areas for improved surgical technique, and re-assessed recurrence following implantation of a quality improvement initiative.

Application of machine learning in a rodent malaria model for rapid, accurate, and consistent parasite counts.

Rodent malaria models serve as important preclinical antimalarial and vaccine testing tools. Evaluating treatment outcomes in these models often requires manually counting parasite-infected red blood cells (iRBCs), a time-consuming process, which can be inconsistent between individuals and labs. We have developed an easy-to-use machine learning (ML)-based software, Malaria Screener R, to expedite and standardize such studies by automating the counting of iRBCs in rodents.

Analysing the Combined Effects of Radiotherapy and Chemokine Receptor 5 Antagonism: Complementary Approaches to Promote T Cell Function and Migration in Oesophageal Adenocarcinoma.

The presence of an immunosuppressive tumour microenvironment in oesophageal adenocarcinoma (OAC) is a major contributor to poor responses. Novel treatment strategies are required to supplement current regimens and improve patient survival. This study examined the immunomodulatory effects that radiation therapy and chemokine receptor antagonism impose on T cell phenotypes in OAC with a primary goal of identifying potential therapeutic targets to combine with radiation to improve anti-tumour responses.

Trimodality therapy versus perioperative chemotherapy in the management of locally advanced adenocarcinoma of the oesophagus and oesophagogastric junction (Neo-AEGIS): an open-label, randomised, phase 3 trial.

Background: The optimum curative approach to adenocarcinoma of the oesophagus and oesophagogastric junction is unknown. We aimed to compare trimodality therapy (preoperative radiotherapy with carboplatin plus paclitaxel [CROSS regimen]) with optimum contemporaneous perioperative chemotherapy regimens (epirubicin plus cisplatin or oxaliplatin plus fluorouracil or capecitabine [a modified MAGIC regimen] before 2018 and fluorouracil, leucovorin, oxaliplatin, and docetaxel [FLOT] subsequently).

Methods: Neo-AEGIS (CTRIAL-IE 10-14) was an open-label, randomised, phase 3 trial done at 24 centres in Europe.

PD-1 blockade attenuates surgery-mediated immunosuppression and boosts Th1 immunity perioperatively in oesophagogastric junctional adenocarcinoma.

Introduction: This timely study assesses the immunosuppressive effects of surgery on cytotoxic Th1-like immunity and investigates if immune checkpoint blockade (ICB) can boost Th1-like immunity in the perioperative window in upper gastrointestinal cancer (UGI) patients.

Methods: PBMCs were isolated from 11 UGI patients undergoing tumour resection on post-operative days (POD) 0, 1, 7 and 42 and expanded using anti-CD3/28 and IL-2 for 5 days in the absence/presence of nivolumab or ipilimumab. T cells were subsequently immunophenotyped flow cytometry to determine the frequency of T helper (Th)1-like, Th1/17-like, Th17-like and regulatory T cell (Tregs) subsets and their immune checkpoint expression profile.

Energy Metabolism, Metabolite, and Inflammatory Profiles in Human Ex Vivo Adipose Tissue Are Influenced by Obesity Status, Metabolic Dysfunction, and Treatment Regimes in Patients with Oesophageal Adenocarcinoma.

Oesophageal adenocarcinoma (OAC) is a poor prognosis cancer with limited response rates to current treatment modalities and has a strong link to obesity. To better elucidate the role of visceral adiposity in this disease state, a full metabolic profile combined with analysis of secreted pro-inflammatory cytokines, metabolites, and lipid profiles were assessed in human ex vivo adipose tissue explants from obese and non-obese OAC patients. These data were then related to extensive clinical data including obesity status, metabolic dysfunction, previous treatment exposure, and tumour regression grades.

Visceral adipose tissue secretome from early and late-stage oesophageal cancer patients differentially affects effector and regulatory T cells.

Aim: Visceral obesity is a key risk factor in the development of oesophagogastric junctional adenocarcinoma (OGJ), predominantly via generation of systemic low grade inflammation. Obesity-induced inflammation promotes resistance to current standards of care, enhancing tumour cell growth and survival. This study investigates the effect of the visceral adipose tissue secretome from OGJ patients with early versus advanced tumours on T-cell immunity and the role of immune checkpoint blockade in enhancing anti-tumour immunity.

Nutrient deprivation and hypoxia alter T cell immune checkpoint expression: potential impact for immunotherapy.

Aim: Use of immune checkpoint blockade to enhance T cell-mediated immunity within the hostile tumour microenvironment (TME) is an attractive approach in oesophageal adenocarcinoma (OAC). This study explored the effects of the hostile TME, including nutrient deprivation and hypoxia, on immune checkpoint (IC) expression and T cell phenotypes, and the potential use of nivolumab to enhance T cell function under such conditions.

Methods And Results: ICs were upregulated on stromal immune cells within the tumour including PD-L2, CTLA-4 and TIGIT.

FLOT and CROSS chemotherapy regimens alter the frequency of CD27 and CD69 T cells in oesophagogastric adenocarcinomas: implications for combination with immunotherapy.

Combining immunostimulatory chemotherapies with immunotherapy is an attractive strategy to enhance treatment responses in oesophagogastric junctional adenocarcinoma (OGJ). This study investigates the immunostimulatory properties of FLOT, CROSS and MAGIC chemotherapy regimens in the context of OGJ using in vitro and ex vivo models of the treatment-naïve and post-chemotherapy treated tumour microenvironment. FLOT and CROSS chemotherapy regimens increased surrogate markers of immunogenic cell death (HMGB1 and HLA-DR), whereas the MAGIC treatment regimen decreased HMGB1 and HLA-DR on OGJ cells (markedly for epirubicin).

Vitamin B supplementation post-gastrectomy: a service closed-loop audit at St. James's Hospital, Dublin.

Background: Vitamin B (VB12) deficiency is a well-described complication post-gastrectomy. It is caused by the loss of parietal cell mass leading to megaloblastic anaemia. This closed-loop audit assesses patient understanding of and adherence with VB12 supplementation guidelines post-gastrectomy.

CROSS Versus FLOT Regimens in Esophageal and Esophagogastric Junction Adenocarcinoma: A Propensity-Matched Comparison.

Background: The FLOT protocol and the CROSS trimodality regimen represent current standards in the management of locally advanced esophageal adenocarcinoma. In the absence of published Randomised Controlled Trial data, this propensity-matched comparison evaluated tolerance, toxicity, impact on sarcopenia and pulmonary physiology, operative complications, and oncologic metrics.

Methods: Two hundred and twenty-two patients, 111 in each arm, were included from 2 high-volume centers.

Impact of radiotherapy on the immune landscape in oesophageal adenocarcinoma.

Background: In the contemporary era of cancer immunotherapy, an abundance of clinical and translational studies have reported radiotherapy (RT) and immunotherapies as a viable option for immunomodulation of many cancer subtypes, with many related clinical trials ongoing. In locally advanced disease, chemotherapy or chemoradiotherapy followed by surgical excision of the tumour remain the principal treatment strategy in oesophageal adenocarcinoma (OAC), however, the use of the host immune system to improve anti-tumour immunity is rapidly garnering increased support in the curative setting.

Aim: To immunophenotype OAC patients' immune checkpoint (IC) expression with and without radiation and evaluate the effects of checkpoint blockade on cell viability.

Acidosis significantly alters immune checkpoint expression profiles of T cells from oesophageal adenocarcinoma patients.

Tumour acidosis contributes to cancer progression by inhibiting anti-tumour immunity. However, the effect of acidosis on anti-tumour T cell phenotypes in oesophageal adenocarcinoma (OAC) is unknown. Therefore, this study investigated the effect of acidosis on anti-tumour T cell profiles and if immune checkpoint blockade (ICB) could enhance anti-tumour T cell immunity under acidosis.

Double-Stranded RNA Viruses Are Released From Inside Small Extracellular Vesicles and Modulate the Exosomal Cargo.

is a parasitic protist that infects the human urogenital tract. During the infection, trichomonads adhere to the host mucosa, acquire nutrients from the vaginal/prostate environment, and release small extracellular vesicles (sEVs) that contribute to the trichomonad adherence and modulate the host-parasite communication. Approximately 40-70% of strains harbor a double-stranded RNA virus called (TVV).

Cooperation between chemotherapy and immune checkpoint blockade to enhance anti-tumour T cell immunity in oesophageal adenocarcinoma.

Response rates to immune checkpoint blockade (ICB) remain low in oesophageal adenocarcinoma (OAC). Combining ICB with immunostimulatory chemotherapies to boost response rates is an attractive approach for converting 'cold' tumours into 'hot' tumours. This study profiled immune checkpoint (IC) expression on circulating and tumour-infiltrating T cells in OAC patients and correlated these findings with clinical characteristics.

The Impact of Esophageal Oncological Surgery on Perioperative Immune Function; Implications for Adjuvant Immune Checkpoint Inhibition.

Background: Immune checkpoint inhibitors (ICIs) are being investigated for their role as an adjunct in the multimodal treatment of esophageal adenocarcinoma (EAC). The most effective time to incorporate ICIs remains unknown. Our study profiles systemic anti-tumor immunity perioperatively to help inform the optimal timing of ICIs into current standards of care for EAC patients.