Musgrove Park Hospital

Abstract Aim To calculate complication and readmission costs of hybrid (HS) versus open surgery (OS) for oesophageal cancer from admission to 24-months, and explore associations between demographic, clinical, and surgical factors. Method Hospital costs for complications and readmissions of patients randomised to HS or OS as part of the ROMIO trial were categorised into four groups: A) costs related to complications of the initial surgery; B) costs related to oesophageal cancer; C) costs unrelated to oesophageal cancer, and D) uncertain. Mean (SD, 95% CI) readmission costs were estimated and compared between HS and OS. A two-part linear mixed model was developed to identify factors associated with the likelihood of readmission and the subsequent increase in readmission costs. Results According to our preliminary findings, among 149 HS and 152 OS patients, the mean readmission costs were higher in the HS cohort (£12,497 vs £9,690). Complication-related readmission costs accounted for 35.5% of total readmission expenditure, where HS patients needed significantly higher mean spending (£4485 vs £3382; p=0.031). Patients undergoing OS had significantly lower odds of complication-related readmission costs (OR=0.54; p=0.016). Older age was associated with a decrease in complication-related readmission costs (OR = 0.96/year; p = 0.013). Although no predictors significantly influenced the magnitude of complication-related readmission, stage III disease suggests a trend toward higher costs (β = 1.95%, p = 0.07). Conclusions OS patients had 22.5% lower total readmission mean costs and significantly lower complication-related readmission costs during the 24-month follow-up. The implications for the broader adoption of HS in NHS practice require discussion.

BackgroundPleural infection remains a significant clinical challenge, requiring hospitalisation, intravenous antibiotics and early chest drain insertion. Medical thoracoscopy (MT), a minimally invasive procedure used electively in the UK for malignant effusions, has demonstrated good outcomes when applied to acute pleural infection in retrospective case series. However, it has not been evaluated as a first-line intervention in the UK in a randomised controlled trial (RCT).ObjectivesThe Studying Pleuroscopy in Routine Pleural Infection Treatment (SPIRIT) trial assessed the feasibility of conducting a full-scale RCT comparing MT with chest drain insertion for acute pleural infection within UK National Health Service (NHS) hospitals.MethodsSPIRIT was an open-label, randomised feasibility trial conducted across seven NHS centres between 2017 and 2019. Adults with suspected pleural infection were prescreened; eligible patients were randomised to either chest drain insertion (control) or MT (performed the same or following day) with 90-day follow-up. The primary outcome was feasibility, assessed through a composite of prescreen, screen and allocation failure rates. Secondary outcomes included inpatient-stay duration, mortality, radiological and microbiological outcomes, second-line interventions, patient-reported outcomes and adverse events.ResultsOf 193 patients prescreened, 181 (93.8%) were excluded due to at least one criterion. Key factors included lack of MT deliverability (49.2%), a not truly infected effusion (45.1%) and contraindications to drainage or study involvement (44.0%). Consequently, the primary feasibility endpoint was not met. All 12 eligible patients were randomised with no attrition. MT lasted 15 min longer than drain insertion, but chest drains remained in situ over 3 days longer (p=0.17) with a longer hospital stay (p=0.57). Radiological improvement, microbiological yield and symptom scores were similar. Adverse events occurred in one control and three MT patients.ConclusionA full-scale RCT is not likely to be feasible in an NHS setting on the proposed protocol. Targeted recruitment from centres equipped for emergency MT may enhance feasibility.Trial registration numberISRCTN98460319.

PurposeHernia repairs are one of the commonest operations performed in the world. In Europe and the United States of America more than half of patients undergoing hernia surgery are overweight or obese; body weight is therefore key modifiable risk factor before surgery. We aimed to identify, appraise, and synthesise the randomized controlled trial (RCT) evidence for any weight loss interventions before any form of hernia surgery.MethodsA search was performed in April 2025 of the PubMed, EMBASE and CENTRAL databases. Meta-analysis was performed using random effects to assess mean difference in weight, and fixed effects for odds ratio of complications. Bias was assessed using the Cochrane Rob2 tool. Certainty effect was assessed using GRADE methodology. This review was registered with PROSPERO (ID 1024784).Results1,707 studies were screened, 20 retrieved, and 4 reports of 3 RCTs included. A total population of 219 patients largely underwent ventral hernia repair, although 2 RCTs also included patients undergoing non-hernia surgery. Interventions comprised very low calorie diets (VLCD), and a multidisciplinary programme. Meta-analysis for VLCD did not show a reduction in weight loss (3.64 kg [95% confidence interval −2.07 – 9.35]) or complications [odds ratio 0.36 (0.1–1.28)]. Risk of bias was “high,” and certainty of effect “very low.”DiscussionDespite the prevalence and importance of obesity in patients undergoing elective hernia repair, and the popularity of weight loss as part of prehabilitation, the randomized evidence of how to effect weight loss, and whether this translates into an improvement in clinical outcomes is minimal. This highlights the urgent need for large and robust RCTs to determine if weight loss before hernia repair is effective in improving outcomes for patients, and how this is best achieved.

This review is based on an updated protocol including network meta-analysis methods and new RoB 2 assessment of a previously published review. Updated protocol 2023 available via https://doi.org/10.1002/14651858.CD015786.

Gastrointestinal stromal tumors (GISTs) are the most common sarcoma subtype. Patients with unresectable or metastatic GISTs harboring the D842V mutation in the PDGFRA gene have a poor prognosis due to intrinsic resistance to imatinib and all other approved tyrosine kinase inhibitors. Avapritinib, targeting this mutation, is the first agent approved for patients with unresectable or metastatic GIST that have the PDGFRA D842V mutation. This study assesses the effectiveness and safety of avapritinib in real-world clinical scenarios involving Spanish patients with this mutation. The AVARWE study is a descriptive, retrospective, multicenter observational study of 21 patients treated with avapritinib across 13 Spanish centers from June 9, 2023, to December 18, 2023. Data collected included patient demographics, disease characteristics, treatment history, and response rates based on RECIST criteria. The main outcomes, progression-free survival (PFS) and overall survival (OS), were measured, with safety assessed through adverse events documentation according to CTCAE criteria. Median PFS 35.6 was months and median OS was 42.2 months, with survival rates at 1, 5, and 3 years demonstrating avapritinib effectiveness. The objective response rate was 76.2% for partial response and 4.8% for complete response. Avapritinib enabled surgical intervention in previously unresectable cases and was generally well-tolerated, with manageable adverse events. Avapritinib extends PFS and OS among patients with PDGFRA D842V-mutant GIST in real-world practice, mirroring pivotal trial outcomes. Its substantial activity supports its use as a first-line therapy for this subgroup. The manageable safety profile reinforces avapritinib viability for routine use. Given the rarity of these cases, it is advised to consult sarcoma-expert units.

An analysis of risk factors affecting wound care clinical trials was performed to develop proactive risk mitigation strategies, and improve the safety and quality of trials conducted. Adherence to study protocol and compliance with regulatory requirements was examined, based on the rate of protocol deviations. Prospective, randomised clinical trials for diabetic foot ulcers (DFUs) and venous leg ulcers (VLUs) were compared for rates/types of deviations from study protocols. Adverse events were analysed in enrolled participants. The rate and patterns of serious adverse events (SAEs) and non-serious adverse events (AEs) were compared between the two wound indications. In all, 15 trials with a total of 261 participants and 223 adverse events were included in the analysis. The DFU group was noted to have a 10.4% higher incidence of SAEs and a 7.3% higher incidence of having any AEs compared with the VLU group. Analysis showed a higher number of deviations (n=325) in VLU trials compared with DFU trials (n=128). Overall, VLUs and DFUs had rates of deviation of 1.9 and 1.4 per enrolled patient, respectively. An understanding of the frequency/types of adverse events can contribute to the development of safety monitoring plans and risk mitigation strategies for wound care trials. Effective training and retention of research coordinators can reduce the number of deviations, and an understanding of the frequency and types of adverse events can inform safety management/risk mitigation plans.

BackgroundOne of the debated indications for paediatric tonsillectomy is unilateral tonsillar enlargement (UTE). The majority of UTE is innocuous in nature; however, concerns exist around a diagnosis of lymphoma, typically found in the presence of other symptoms.MethodsA retrospective case series analysis of all paediatric tonsillectomy specimens at Bristol Children’s Hospital between January 2006 and January 2023 was undertaken.ResultsFour (1.3%) lymphoma diagnoses were identified from the 319 patients who underwent tonsillectomy for UTE. Three patients had localised disease and one patient had systemic infiltration of disease. All patients presented with other signs of malignancy including cervical lymphadenopathy (100%), alteration of appearance of tonsil including colour or visible lesion (75%), snoring (75%), dysphagia (50%), recurrent fever (25%) and weight loss (25%).ConclusionsWe recommend active monitoring of asymptomatic isolated UTE. Diagnostic tonsillectomy should be performed in patients with UTE and cervical lymphadenopathy and/or constitutional symptoms and/or altered tonsillar appearance.

Abstract Background: Targeting melanoma by T cells drives anti-tumour responses. Previously in a phase 1/2 study we successfully evaluated a DNA vaccine, SCIB1, incorporating CD8 and CD4 T cell epitopes from TRP-2/gp100 into an antibody framework to allow Fc targeting of activated dendritic cells. In stage 3/4 unresectable melanoma patients receiving SCIB1 as a monotherapy we showed a 60% disease control rate (DCR) and 88% of patients treated with SCIB1 post tumour resection remained disease free for 5 years. Checkpoint inhibitor (CPI) therapies are now standard of care for melanoma, with nivolumab and ipilimumab being the most used combination. The current Phase 2 SCOPE trial tests the hypothesis that unresectable patients may have an improved response when SCIB1 is combined with CPI. In patients enrolled in this trial, the induction of SCIB1 specific T cell responses is also being evaluated. Methods: Patients were treated with nivolumab, ipilimumab and SCIB1 (8mg) i.m. using needle-free injection at a fixed dosing schedule for a total of 10 doses over 24 months. CPI therapy was administered i.v. in accordance with their respective SmPC. Vaccine specific T cell responses to SCIB1 were assessed via a combination of IFNγ ELISpot, single-cell RNA- & TCR-seq and TCR repertoire analysis. Results: From 41 patients enrolled in the SCOPE study, we will present data on functional T cell responses to the TRP2 and gp100 peptides incorporated within SCIB1. Characterization of these T cell responses showed SCIB1 induces both CD4 and CD8 mediated responses. For three patients, we have isolated CD8 TCRs which are reactive to the SCIB1 epitopes incorporated in the vaccine. Single-cell RNA- & TCR-seq was performed on sorted CD8+ IFNγ+ cells with RNA-seq analysis revealing several expanded TCR clonotypes in CD8 T cell populations with a cytotoxic transcriptional profile. Using Lentivirus-TCR transduced T cells we have successfully shown that six isolated CD8 TCRs react specifically to the TRP-2 or gp100 epitopes incorporated into SCIB1. We have characterized the T cell responses and have mapped the minimal epitope and the presenting HLA allele. Bulk TCR repertoire sequencing revealed that, in two out of three patients, the isolated SCIB1 specific TCRs were undetectable in peripheral CD8 T cells collected from pre-vaccination samples. The same TCRs were detectable in the post-vaccination CD8 TCR repertoire. Conclusions: SCIB1 in combination with nivolumab and ipilimumab consistently induced functional CD4 and CD8 T cell responses, with demonstratable vaccine induced expansion of SCIB1 specific TCR clonotypes. Citation Format: Joseph Chadwick, Gaëlle Cane, Sabaria Shah, Katie Mann, Patrick Copeland, Daisy Weston, Jordan Wright, Leanne Toon, Heather Shaw, Poulam Patel, Miranda Payne, Satish Kumar, Sarah Danson, Martin Highley, Clare Barlow, Kellati Prasad, Ioannis Karydis, Maria Marples, Kate Young, Pippa Corrie, Robert Miller, Rachael Metheringham, Georgia Goodhew, Nermeen Varawalla, Samantha Paston, Lindy Durrant. A DNA plasmid melanoma cancer vaccine, SCIB1, combined with nivolumab + ipilimumab induces functional CD4 and CD8 T cell responses in patients with advanced unresectable melanoma [abstract]. In: Proceedings of the AACR IO Conference: Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2025 Feb 23-26; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(2 Suppl):Abstract nr B119.