Publications by authors named "Timothy Underwood"

Background: Prehabilitation is safe, feasible and may improve a range of outcomes in patients with oesophago-gastric cancer (OGC). Recent studies have suggested the potential of prehabilitation to improve body composition, sarcopenia and physical fitness, reduce surgical complications and improve quality of life. Despite this, prehabilitation services are not offered throughout all OGC centres in the UK.

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Objective: To understand the CD8+ tumour infiltrating lymphocyte (TIL) compartment of oesophageal adenocarcinoma (OAC) with regards to markers of lymphocyte exhaustion, tissue residency and to identify possible reasons behind differential responses to therapy.

Design: Tumour samples from 44 patients undergoing curative resection for OAC were assessed by flow cytometry for presence of antigen-experienced TILs and markers of activation and exhaustion. Populations of PD-1 and CD39 positive OAC TILs were sorted, and bulk RNA sequencing undertaken using a modified SmartSeq2 protocol.

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Article Synopsis
  • The study investigated the risks of lymph node metastasis (LNM) and treatment outcomes in patients with early esophago-gastric (EG) adenocarcinoma, focusing on the effectiveness of endoscopic resection (ER) versus radical surgery.
  • A retrospective analysis was conducted using data from 1,601 patients across 26 UK centers, revealing that the overall LNM rate was 13.5% and highlighting certain tumor characteristics that may indicate higher risks, although these factors did not predict LNM rates or survival outcomes significantly.
  • The findings suggest a need to reevaluate the predictive factors for LNM in early EG adenocarcinoma and emphasize the importance of further research to better identify patients suitable for either organ-preserving
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Background: Clinician-led quality control into oncological decision-making is crucial for optimising patient care. Explainable artificial intelligence (XAI) techniques provide data-driven approaches to unravel how clinical variables influence this decision-making. We applied global XAI techniques to examine the impact of key clinical decision-drivers when mapped by a machine learning (ML) model, on the likelihood of receiving different oesophageal cancer (OC) treatment modalities by the multidisciplinary team (MDT).

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Article Synopsis
  • Oesophagogastric cancer surgery outcomes are generally poor, leading researchers to investigate the effectiveness of cardiopulmonary exercise testing (CPET) in predicting postoperative results, especially after neoadjuvant treatments.
  • A study included 611 patients from seven UK centers, analyzing the relationship between peak oxygen uptake (VO peak) and one-year survival, finding no significant correlation, but noting that anaerobic threshold measures related to ideal body weight were predictive of three-year survival.
  • Key factors influencing survival included tumor characteristics and major complications, with specific CPET metrics showing some predictive value but not universally across the entire cohort.
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Background: Rhabdomyosarcomas (RMS) are predominantly paediatric sarcomas thought to originate from muscle precursor cells due to impaired myogenic differentiation. Despite intensive treatment, 5-year survival for patients with advanced disease remains low (< 30%), highlighting a need for novel therapies to improve outcomes. Differentiation therapeutics are agents that induce differentiation of cancer cells from malignant to benign.

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Neuroblastoma is one of the commonest extra-cranial pediatric tumors, and accounts for over 15% of all childhood cancer mortality. Risk stratification for children with neuroblastoma is based on age, stage, histology, and tumor cytogenetics. The majority of patients are considered to have high-risk neuroblastoma, for which the long-term survival is less than 50%.

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Background: Rising workflow pressures within the oesophageal cancer (OC) multidisciplinary team (MDT) can lead to variability in decision-making, and health inequality. Machine learning (ML) offers a potential automated data-driven approach to address inconsistency and standardize care. The aim of this experimental pilot study was to develop ML models able to predict curative OC MDT treatment decisions and determine the relative importance of underlying decision-critical variables.

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Pseudomyxoma peritonei (PMP) is a rare, progressive, slowly growing neoplastic condition which is poorly understood, with a 5-year progression-free survival rate as low as 48%. PMP is most commonly caused by appendiceal mucinous neoplasms (AMN), and understanding their genetic biology and pathogenicity may allow for the development of better novel systemic treatments to target key deleterious mutations and the implicated pathways. The primary aim of this systematic review was to identify the genetic profile of histologically confirmed human PMP or AMN samples.

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Background: The complexity of the upper gastrointestinal (UGI) multidisciplinary team (MDT) is continually growing, leading to rising clinician workload, time pressures, and demands. This increases heterogeneity or 'noise' within decision-making for patients with oesophageal cancer (OC) and may lead to inconsistent treatment decisions. In recent decades, the application of artificial intelligence (AI) and more specifically the branch of machine learning (ML) has led to a paradigm shift in the perceived utility of statistical modelling within healthcare.

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The ongoing evolution of technology has facilitated the global research community to rapidly escalate the constant development of novel advancements in science. At the forefront of such achievements in the field of photocatalysis is the utilisation, and in oftentimes, the adaptation of modern instrumentation to understand photo-physical properties of complex heterostructures. For example, coupling in-situ X-ray Raman scattering spectroscopy for real-time degradation of catalytic materials.

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The chemotherapy resistance of esophageal adenocarcinomas (EACs) is underpinned by cancer cell extrinsic mechanisms of the tumor microenvironment (TME). We demonstrate that, by targeting the tumor-promoting functions of the predominant TME cell type, cancer-associated fibroblasts (CAFs) with phosphodiesterase type 5 inhibitors (PDE5i), we can enhance the efficacy of standard-of-care chemotherapy. In ex vivo conditions, PDE5i prevent the transdifferentiation of normal fibroblasts to CAF and abolish the tumor-promoting function of established EAC CAFs.

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Article Synopsis
  • - This study explores how neoadjuvant therapy (NAT) impacts skeletal muscle mass, myosteatosis, and fitness in patients with oesophago-gastric cancer, highlighting that all these factors are linked to postoperative outcomes.
  • - Among 184 patients, significant decreases in muscle mass, radiation-attenuation, and fitness were observed after NAT; however, only the pectoralis muscle mass effectively correlated with peak exercise performance.
  • - The findings indicate that while sarcopenia and myosteatosis didn't impact morbidity or survival, better cardiorespiratory fitness (measured through CPET) is crucial for improving short-term survival post-surgery.
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Oesophageal adenocarcinoma (OAC) has a dismal prognosis, where curable disease occurs in less than 40% of patients, and many of those with incurable disease survive for less than a year from diagnosis. Despite the widespread use of systematic chemotherapy in OAC treatment, many patients receive no benefit. New treatments are urgently needed for OAC patients.

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Background: Variation in the approach, radicality, and quality of gastroesophageal surgery impacts patient outcomes. Pathological outcomes such as lymph node yield are routinely used as surrogate markers of surgical quality, but are subject to significant variations in histopathological evaluation and reporting. A multi-society consensus group was convened to develop evidence-based recommendations for the standardized assessment of gastroesophageal cancer specimens.

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Purpose Of Review: This review examines current developments and controversies in the multimodal management of oesophageal cancer, with an emphasis on surgical dilemmas and outcomes from the surgeon's perspective.

Recent Findings: Despite the advancement of oncological neoadjuvant treatments, there is still no consensus on what regimen is superior. The majority of patients may still fail to respond to neoadjuvant therapy and suffer potential harm without any survival advantage as a result.

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Background: The United States Department of Veterans Affairs established a program in which actors incognito portray veterans experiencing homelessness with pre-determined needs to identify barriers to access and services at community-based organizations.

Methods: From 2017 to 2019, actors who varied in gender, skin color and age portrayed one of three scripts at all VA Community-Based Resource and Referral Centers (CRRCs) serving veterans experiencing homelessness in 30 cities and completed an evaluative survey. They carried authentic VA identification and were registered in a VA patient database for each identity.

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Objective: The aim of this study was to develop a predictive model for overall survival after esophagectomy using pre/postoperative clinical data and machine learning.

Summary Background Data: For patients with esophageal cancer, accurately predicting long-term survival after esophagectomy is challenging. This study investigated survival prediction after esophagectomy using a RandomSurvival Forest (RSF) model derived from routine data from a large, well-curated, national dataset.

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Boerhaave's syndrome is a life-threatening spontaneous perforation of the esophagus associated with significant morbidity and mortality. Historically, thoracotomy has been the mainstay of treatment, but is associated with high morbidity and pain. Minimally invasive approaches provide alternative treatment possibilities.

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Article Synopsis
  • Esophageal cancer is on the rise and has a poor prognosis, with treatments like neoadjuvant chemotherapy (CT) and chemoradiotherapy (CRT) being compared due to a lack of strong trial data.
  • Researchers analyzed outcomes from 284 patients who received either CT or CRT prior to surgery using a statistical method to ensure fair comparison.
  • Results showed no significant difference in postoperative complications or survival between the two groups, but CRT led to better tumor response and higher rates of successful tumor removal (R0 resection), indicating that better local control might not improve overall survival.
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The development of an aqueous silver-sodium/alizarin red sensitised zinc oxide system has been reported to oxidise a range of both aromatic and aliphatic alcohols to aldehydes. Furthermore, photoluminescence spectroscopy validated the electron quenching effect of zinc oxide's defect sites after surface sensitising the metal-oxide with alizarin red. Powder diffuse reflectance UV/Vis data further substantiated the visible-light attenuated properties of alizarin red sensitised zinc oxide, and hence justification for its visible light reactivity towards alcohol oxidations.

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Objective: Current strategies to guide selection of neoadjuvant therapy in oesophageal adenocarcinoma (OAC) are inadequate. We assessed the ability of a DNA damage immune response (DDIR) assay to predict response following neoadjuvant chemotherapy in OAC.

Design: Transcriptional profiling of 273 formalin-fixed paraffin-embedded prechemotherapy endoscopic OAC biopsies was performed.

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