RSS 1.0Cancer and Associated Specialties
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LAsting Symptoms after Oesophageal Resectional Surgery (LASORS): Multicentre validation cohort studyBackground: Long-term symptom burden and health-related quality-of-life outcomes after curative oesophageal cancer treatment are poorly understood. Existing tools are cumbersome and do not address the post-treatment population specifically. The aim of this study was to validate the six-symptom LASORS tool for identifying patients after curative oesophageal cancer treatment with poor health-related quality of life and to assess its clinical utility. Method(s): Between 2015 and 2019, patients from 15 UK centres who underwent curative-intent oesophageal cancer treatment, and were disease-free at least 1 year after surgery, were invited to participate in the study and complete LASORS and European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-OG25 questionnaires. Receiver operating characteristic curve analysis was used to examine the accuracy of the LASORS tool for identifying patients with poor health-related quality of life. Result(s): A total of 263 patients completed the questionnaire. Four of the six LASORS symptoms were associated with poor health-related quality of life: reduced energy (OR 2.13 (95% c.i. 1.45 to 3.13)); low mood (OR 1.86 (95% c.i. 1.20 to 2.88)); diarrhoea more than three times a day unrelated to eating (OR 1.48 (95% c.i. 1.06 to 2.07)); and bloating or cramping after eating (OR 1.35 (95% c.i. 1.03 to 1.77)). The LASORS tool showed good diagnostic accuracy with an area under the receiver operating characteristic curve of 0.858 for identifying patients with poor health-related quality of life. Conclusion(s): The six-symptom LASORS tool generated a reliable model for identification of patients with poor health-related quality of life after curative treatment for oesophageal cancer. This is the first tool of its kind to be prospectively validated in the post-esophagectomy population. Clinical utility lies in identification of patients at risk of poor health-related quality of life, ease of use of the tool, and in planning survivorship services.Copyright © 2025 The Author(s).
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Post-cancer treatment reflections by patients concerning the provisions and support required for a prehabilitation programmeBACKGROUND: Evidence suggests that physical fitness interventions, mental health support and nutritional advice before surgery (prehabilitation) could reduce hospital stay and improve quality of life of patients with cancer. In this study we captured the opinions of a group of patients with cancer undergoing these interventions after treatment to discover what a prehabilitation programme should encompass. METHOD(S): Patients from the Cancer and Rehabilitation Exercise (CARE) programme based in Nottingham took part in a 26-point online questionnaire about the design of prehabilitation programmes. RESULT(S): The questionnaire was completed over a 2-week period in December 2021 by 54 patients from the CARE programme. Their responses were as follows: 44 (81.5%) participants would have participated in prehabilitation had it been available to them and 28 (51.9%) ranked physical exercise as the most important component. Forty (74.1%) participants believed the counselling aspect of prehabilitation would have contributed to a successful outcome and 35 (64.8%) thought dietary advice would have benefitted them before surgery. Thirty-one (57.4%) participants preferred the programme to take place in a fitness centre, rather than at home or hospital and 43 (79.6%) would have liked to have known about prehabilitation from their doctor at the time of diagnosis. CONCLUSION(S): Patients are interested in prehabilitation to become more physically fit and mentally prepared for surgery. They expressed the need for a focus on physical exercise, counselling to improve mental health and personalised nutritional advice. Tailoring a prehabilitation programme, with input from patients, could contribute to improving patient outcomes following cancer treatments.Copyright © 2023. The Author(s).
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COLOFIT: Development and internal-external validation of models using age, sex, faecal immunochemical and blood tests to optimise diagnosis of colorectal cancer in symptomatic patientsBackground: Colorectal cancer (CRC) is the third most common cancer in the United Kingdom and the second largest cause of cancer death. Aim(s): To develop and validate a model using available information at the time of faecal immunochemical testing (FIT) in primary care to improve selection of symptomatic patients for CRC investigations. Method(s): We included all adults (>= 18 years) referred to Nottingham University Hospitals NHS Trust between 2018 and 2022 with symptoms of suspected CRC who had a FIT. Predicted 1-year CRC diagnosis were calculated, and externally validated, using Cox proportional hazards modelling with selected multiple fractional polynomial transformations for age, faecal haemoglobin concentration (f-Hb) value, mean corpuscular volume (MCV), platelet count and sex. Result(s): At a CRC risk threshold of 0.6% (equivalent to f-Hb = 10 mug Hb/g (mug/g)) overall performance of the validated model across age strata using Harrell's C index was >= 0.91% (overall C-statistic 93%, 95% CI 92%-95%) with acceptable calibration. Using this model yields similar numbers of detected and missed cancers, but requires ~20% fewer investigations than a f-Hb >= 10 mug/g strategy. For approximately 100,000 people per year with symptoms of suspected CRC, we predict it might save > 4500 colonoscopies with no evidence that more cancers would be missed if we used our model compared to using FIT f-Hb >= 10 mug/g. Conclusion(s): Including age, sex, MCV, platelets and f-Hb in a survival analysis model to predict the risk of CRC yields greater diagnostic utility than a simple binary cut off f-Hb >= 10 mug/g.Copyright © 2025 The Author(s). Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.
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Systematic review: Mortality associated with raised faecal immunochemical test and positive faecal occult blood resultsBackground: Faecal haemoglobin (f-Hb) testing is used in colorectal cancer (CRC) screening and increasingly to guide the investigation in patients with symptoms suggestive of CRC. Studies have demonstrated increased mortality with raised f-Hb. Aim(s): To assess the association of raised f-Hb with all-cause, non-CRC (any cause excluding CRC) and cause-specific mortality. Method(s): We searched Medline and Embase on 9 February 2024 to identify papers reporting mortality after faecal immunochemical (FIT) or guaiac faecal occult blood tests (gFOBT). The primary outcome was all-cause mortality following a positive compared to a negative test. Result(s): The search identified 3155 papers. Ten met the inclusion criteria: three reported gFOBT and seven reported FIT results, as screening tests. These reported a total of 14,687,625 f-Hb results. Elevated f-Hb was associated with an increased risk of all-cause, non-CRC and cause-specific mortality including death from cardiovascular, digestive and respiratory diseases. Crude risk ratios for all-cause mortality with a positive versus negative test were derived from six papers (three reporting gFOBT, three FIT). An increased risk was demonstrated in five, with RRs ranging from 1.11 (95% CI: 1.06-1.16) to 2.95 (95% CI: 2.85-3.05). For non-CRC mortality risk, RRs ranged from 1.09 (95% CI: 1.04-1.15) to 2.79 (95% CI: 2.70-2.89). We did not perform meta-analysis due to a limited number of papers reporting suitable results for each type of f-Hb test. Conclusion(s): All-cause, non-CRC and cause-specific mortality appear higher in those with raised f-Hb. Population-based studies are warranted to elicit whether this association occurs in symptomatic patients.Copyright © 2024 The Author(s). Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.
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'Low' faecal immunochemical test (FIT) colorectal cancer: A 4-year comparison of the Nottingham '4F' protocol with FIT10 in symptomatic patientsAim: The aim of this work was to evaluate colorectal cancer (CRC) outcomes after 'low' (sub-threshold) faecal immunochemical test (FIT) results in symptomatic patients tested in primary care. Method(s): This work comprised a retrospective audit of 35 289 patients with FIT results who had consulted their general practitioner with lower gastrointestinal symptoms and had subsequent CRC diagnoses. The Rapid Colorectal Cancer Diagnosis pathway was introduced in November 2017 to allow incorporation of FIT into clinical practice. The local '4F' protocol combined FIT results with blood tests and digital rectal examination (DRE): FIT, full blood count, ferritin and finger DRE]. The outcome used was detection rates of CRC, missed CRC and time to diagnosis in local 4F protocols for patients with a subthreshold faecal haemoglobin (fHb) result compared with thresholds of 10 and 20 mug Hb/g faeces. Result(s): A single threshold of 10 mug Hb/g faeces identifies a population in whom the risk of CRC is 0.2%, but this would have missed 63 (10.5%) of 599 CRCs in this population. The Nottingham 4F protocol would have missed fewer CRCs 42 of 599 (7%)] despite using a threshold of 20 mug Hb/g faeces for patients with normal blood tests. Subthreshold FIT results in patients subsequently diagnosed with a palpable rectal tumour yielded the longest delays in diagnosis. Conclusion(s): A combination of FIT with blood results and DRE (the 4F protocol) reduced the risk of missed or delayed diagnosis. Further studies on the impact of such protocols on the diagnostic accuracy of FIT are expected. The value of adding blood tests to FIT may be restricted to specific parts of the fHb results spectrum.Copyright © 2024 The Authors. Colorectal Disease published by John Wiley & Sons Ltd on behalf of Association of Coloproctology of Great Britain and Ireland.
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Point of care testing of Influenza A/B and RSV in an adult respiratory assessment unit is associated with improvement in isolation practices and reduction in hospital length of stayIntroduction. Every winter seasonal influenza and other viral respiratory infections increase pressure on the health services and are associated with nosocomial infection and morbidity. Aim. To compare provision of point-of-care (POC) testing with laboratory-based testing for influenza and RSV detection on an adult respiratory assessment unit to assess the impact on isolation practices and length of stay (LOS). Methodology. Prospective interrupted 'on-off' study in adults admitted to the respiratory unit between December 2018 and April 2019 with a suspected respiratory tract infection. Nasopharyngeal samples were tested using either the GeneXpert rapid POC test for influenza and RSV (on-period), or were sent to the laboratory for multiplex PCR testing against a panel of 12 respiratory viruses (off-period). Outcome measures were time to patient isolation for infection control, LOS and turnaround time from admission to test results. Results. Of 1145 patients evaluated, 755 were tested with POC and 390 with laboratory multiplex; a respiratory virus was identified in 164 (21.7 %) and 138 (35.4 %) patients respectively. A positive POC test was associated with a shorter time to isolation (mean difference 16.9 h, PP=0.05,) and shorter turnaround time (mean difference 28.3 h, PConclusion. Use of GeneXpert POC testing for Flu/RSV is associated with rapid reporting of results with significant improvements in isolation practices and reductions in LOS.
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Expression of Cathepsin D in early-stage breast cancer and its prognostic and predictive valuePurpose: Cathepsin D is a proteolytic enzyme that is normally localized in the lysosomes and is involved in the malignant progression of breast cancer. There are conflicting results regarding Cathepsin D significance as prognostic and predictor marker in breast cancer. This study aimed to evaluate the expression and prognostic significance of Cathepsin D in early-stage breast cancer. Method(s): Expression of Cathepsin D was assessed by immunohistochemical staining of tissue microarrays, in a large well-characterized series of early-stage operable breast cancer (n = 954) from Nottingham Primary Breast Carcinoma Series between the period of 1988 and 1998 who underwent primary surgery. Correlation of Cathepsin D expression with clinicopathological parameters and prognosis was evaluated. Result(s): Cathepsin D expression was positive in 71.2% (679/954) of breast cancer tumours. Positive expression of Cathepsin D was significantly associated with high histological grade (p = 0.007), pleomorphism (p = 0.002), poor Nottingham Prognostic Index (NPI) score (p < 0.002), recurrence (p = 0.005) and distant metastasis (p < 0.0001). Kaplan-Meier analysis showed that Cathepsin D expression was significantly associated with shorter breast cancer-specific survival (p = 0.001), higher risk of recurrence (p = 0.001) and distant metastasis (p < 0.0001). ER-positive tumours expressing Cathepsin D and treated with tamoxifen demonstrated a significantly higher risk of distant metastasis. Conclusion(s): Cathepsin D expression significantly predicts poor prognosis in breast cancer and is associated with variables of poor prognosis and shorter outcome. The strong association of Cathepsin D with aggressive tumour characteristics and poor outcomes warrants further research of its potential as a therapeutic target The results also suggest a possible interaction between Cathepsin D and tamoxifen therapy in ER-positive breast cancer which needs further investigation to elucidate the underlying mechanisms.Copyright © The Author(s) 2024.
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Predicting time to asystole following withdrawal of life-sustaining treatment: A systematic reviewThe planned withdrawal of life-sustaining treatment is a common practice in the intensive care unit for patients where ongoing organ support is recognised to be futile. Predicting the time to asystole following withdrawal of life-sustaining treatment is crucial for setting expectations, resource utilisation and identifying patients suitable for organ donation after circulatory death. This systematic review evaluates the literature for variables associated with, and predictive models for, time to asystole in patients managed on intensive care units. We conducted a comprehensive structured search of the MEDLINE and Embase databases. Studies evaluating patients managed on adult intensive care units undergoing withdrawal of life-sustaining treatment with recorded time to asystole were included. Data extraction and PROBAST quality assessment were performed and a narrative summary of the literature was provided. Twenty-three studies (7387 patients) met the inclusion criteria. Variables associated with imminent asystole ( Copyright © 2024 The Authors. Anaesthesia published by John Wiley & Sons Ltd on behalf of Association of Anaesthetists.
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Decision-making about premortem interventions for donation: Navigating legal and ethical complexitiesPremortem interventions (PMIs) for organ donation play a vital role in preserving opportunities for deceased donation or increasing the chances of successful transplantation of donor organs. Although ethical considerations relating to use of particular PMIs have been well explored, the ethical and legal aspects of decision-making about the use of PMIs have received comparatively little attention. In many countries, there is significant uncertainty regarding whether PMIs are lawful or, if they are, who can authorize them. Furthermore, emphasis on consideration of therapeutic goals in substitute decision-making frameworks may discourage consideration of donation goals. In this article, we examine the fundamental questions of who should have the authority to make decisions about the use of PMIs on behalf of a potential donor and how such decisions should be made. We draw on international examples of legal reform that have sought to clarify the legal position in relation to administering PMIs and identify potential elements of an effective regulatory model for PMIs. In doing so, we argue that reforms are needed in many countries to provide legal certainty for clinicians who are responsible for supporting decision-making about PMIs and to ensure that the goals and preferences of potential donors are accorded due consideration in the decision-making process. Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.
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Donor time to death and kidney transplant outcomes in the setting of a 3-hour minimum wait policyImportance: Lengthening waiting lists for organ transplant mandates the development of strategies to expand the deceased donor pool. Due to concerns regarding organ viability, most organ donation organizations internationally wait no longer than 1 to 2 hours for potential donation after circulatory death (DCD), possibly underutilizing an important organ source; UK policy mandates a minimum 3-hour wait time. Objective: To assess whether time to death (TTD) from withdrawal of life-sustaining treatment (WLST) is associated with kidney transplant outcomes. Design, Setting, and Participants: This population-based cohort study used data from the prospectively maintained UK Transplant Registry from all 23 UK kidney transplant centers from January 1, 2013, to December 31, 2021; follow-up was until the date of data extraction (October 2023). Participants comprised 7183 adult recipients of DCD kidney-alone transplants. Exposure: Duration of TTD, defined as time from WLST to donor mechanical asystole. Main Outcomes and Measures: Primary outcome was 12-month estimated glomerular filtration rate (eGFR; for the main eGFR model, variables with significant right skew histogram visual assessment] were analyzed on the log2 scale), with secondary outcomes of delayed graft function and graft survival (censored at death or 5 years). Results: This study included 7183 kidney transplant recipients (median age, 56 years IQR, 47-64 years]; 4666 men 65.0%]). Median donor age was 55 years (IQR, 44-63 years). Median TTD was 15 minutes (range, 0-407 minutes), with 885 kidneys transplanted from donors with TTD over 1 hour and 303 kidneys transplanted from donors with TTD over 2 hours. Donor TTD was not associated with recipient 12-month eGFR on adjusted linear regression (change per doubling of TTD, -0.25; 95% CI, -0.68 to 0.19; P = .27), nor with delayed graft function (adjusted odds ratio, 1.01; 95% CI, 0.97-1.06; P = .65) or graft survival (adjusted hazard ratio, 1.00; 95% CI, 0.95-1.07; P = .92). These findings were confirmed with restricted cubic spline models (assessing nonlinear associations) and tests of interaction (including normothermic regional perfusion). In contrast, donor asystolic time, cold ischemic time, and reperfusion time were independently associated with outcomes. Compared with a theoretical 1-hour maximum wait time, the UK policy (minimum 3-hour wait time) has been associated with 885 extra DCD transplants compared with 6298 transplants (14.1% increase). Conclusions and Relevance: In this cohort study of DCD kidney recipients, donor TTD was not associated with posttransplant outcomes, in contrast to subsequent ischemic times. Altering international transplant practice to mandate minimum 3-hour donor wait times could substantially increase numbers of kidney transplants performed without prejudicing outcomes.
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When is directed deceased donation justified? Practical, ethical, and legal issuesThis paper explores whether directed deceased organ donation should be permitted, and if so under which conditions. While organ donation and allocation systems must be fair and transparent, might it be "one thought too many" to prevent directed donation within families? We proceed by providing a description of the medical and legal context, followed by identification of the main ethical issues involved in directed donation, and then explore these through a series of hypothetical cases similar to those encountered in practice. Ultimately, we set certain conditions under which directed deceased donation may be ethically acceptable. We restrict our discussion to the allocation of organs to recipients already on the waiting list. Copyright © The Intensive Care Society 2024.
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A single-center exploration of attitudes to deceased organ donation over time among healthcare staff in intensive careBackground: Changes to deceased organ donation in the United Kingdom, including establishment of the specialist nurse for organ donation (SNOD) role, have resulted in increased numbers of donations. Have increasing numbers of donations altered attitudes among intensive care unit (ICU) healthcare professionals (ICU staff) to organ donation over time? Methods: A written survey of ICU staff at Nottingham University Hospitals National Health Service Trust was conducted across 2 wk in 2015, 2018, and 2020 (pre-COVID-19). Participants were asked to submit descriptors (words/phrases) they associated with 3 aspects of donation: donation after brain death (DBD), donation after circulatory death (DCD), and SNOD role. Three independent and blinded assessors categorized the descriptors as positive or negative in favorability. Thematic analysis was used to identify trends within each group of descriptors. Results: Across the 3 surveys, 281 responses were returned, containing a total of 2095 descriptors. Positive descriptors were found in 65% of DBD responses, 46% of DCD responses, and 92% of SNOD role. Over time, there was some evidence of increased polarization of opinion for DCD and to a smaller degree DBD. Attitude toward the SNOD role remained consistently highly favorable over time. Thematic analysis was correlated with the assessor favorability ratings to identify specific factors for positive or negative attitudes; this demonstrated the themes that were the most common causes of positive or negative attributions for each aspect of organ donation. Conclusions: ICU staff were found to be highly favorably positive toward the SNOD role, positive toward DBD, and negative toward DCD. Although we found broadly positive perceptions of the benefits of deceased organ donation, negative attitudes toward DCD centered on timescale and complexity of the donation process. Measurement of staff attitudes to organ donation may allow targeted interventions that support staff and improve patient and family care through the organ donation process. Copyright © 2023 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.
