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Background: Outcomes after oesophagogastric cancer surgery remain poor. Cardiopulmonary exercise testing (CPET) used for risk stratification before oesophagogastric cancer surgery is based on conflicting evidence. This study explores the relationship between CPET and postoperative outcomes, specifically for patients undergoing neoadjuvant treatment. Methods: Patients undergoing oesophagogastric cancer resection and CPET (pre- or post-neoadjuvant treatment, or both) were retrospectively enrolled into a multicentre pooled cohort study. Oxygen uptake at peak exercise (VO2 peak) was compared with 1-yr postoperative survival. Secondary analyses explored relationships between patient characteristics, tumour pathology characteristics, CPET variables (absolute, relative to weight, ideal body weight, and body surface area), and postoperative outcomes (morbidity, 1-yr and 3-yr survival) were assessed using logistic regression analyses. Results: Seven UK centres recruited 611 patients completing a 3-yr postoperative follow-up period. Oesophagectomy was undertaken in 475 patients (78%). Major complications occurred in 25%, with 18% 1-yr and 43% 3-yr mortality. No association between VO2 peak or other selected CPET variables and 1-yr survival was observed in the overall cohort. In the overall cohort, the anaerobic threshold relative to ideal body weight was associated with 3-yr survival (P=0.013). Tumour characteristics (ypT/ypN/tumour regression/lymphovascular invasion/resection margin; P<0.001) and Clavien-Dindo ≥3a (P<0.001) were associated with 1-yr and 3-yr survival. On subgroup analyses, pre-neoadjuvant treatment CPET; anaerobic threshold (absolute; P=0.024, relative to ideal body weight; P=0.001, body surface area; P=0.009) and VE/VCO2 at anaerobic threshold (P=0.026) were associated with 3-yr survival. No other CPET variables (pre- or post-neoadjuvant treatment) were associated with survival. Conclusions: VO2 peak was not associated with 1-yr survival after oesophagogastric cancer resection. Tumour characteristics and major complications were associated with survival; however, only some selected pre-neoadjuvant treatment CPET variables were associated with 3-yr survival. CPET in this cohort of patients demonstrates limited outcome predictive precision. Clinical trial registration: NCT03637647.
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BACKGROUND: National and international amalgamation of genomic data offers opportunity for research and audit, including analyses enabling improved classification of variants of uncertain significance. Review of individual-level data from National Health Service (NHS) testing of cancer susceptibility genes (2002-2023) submitted to the National Disease Registration Service revealed heterogeneity across participating laboratories regarding (1) the structure, quality and completeness of submitted data, and (2) the ease with which that data could be assembled locally for submission. METHODS: In May 2023, we undertook a closed online survey of 51 clinical scientists who provided consensus responses representing all 17 of 17 NHS molecular genetic laboratories in England and Wales which undertake NHS diagnostic analyses of cancer susceptibility genes. The survey included 18 questions relating to 'next-generation sequencing workflow' (11), 'variant classification' (3) and 'phenotypical context' (4). RESULTS: Widely differing processes were reported for transfer of variant data into their local LIMS (Laboratory Information Management System), for the formatting in which the variants are stored in the LIMS and which classes of variants are retained in the local LIMS. Differing local provisions and workflow for variant classifications were also reported, including the resources provided and the mechanisms by which classifications are stored. CONCLUSION: The survey responses illustrate heterogeneous laboratory workflow for preparation of genomic variant data from local LIMS for centralised submission. Workflow is often labour-intensive and inefficient, involving multiple manual steps which introduce opportunities for error. These survey findings and adoption of the concomitant recommendations may support improvement in laboratory dataflows, better facilitating submission of data for central amalgamation.
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Laboratórios , Neoplasias , Humanos , Fluxo de Trabalho , Medicina Estatal , Genômica , Reino UnidoRESUMO
OBJECTIVE: To describe national patterns of National Health Service (NHS) analysis of mismatch repair (MMR) genes in England using individual-level data submitted to the National Disease Registration Service (NDRS) by the NHS regional molecular genetics laboratories. DESIGN: Laboratories submitted individual-level patient data to NDRS against a prescribed data model, including (1) patient identifiers, (2) test episode data, (3) per-gene results and (4) detected sequence variants. Individualised per-laboratory algorithms were designed and applied in NDRS to extract and map the data to the common data model. Laboratory-level MMR activity audit data from the Clinical Molecular Genetics Society/Association of Clinical Genomic Science were used to assess early years' missing data. RESULTS: Individual-level data from patients undergoing NHS MMR germline genetic testing were submitted from all 13 English laboratories performing MMR analyses, comprising in total 16 722 patients (9649 full-gene, 7073 targeted), with the earliest submission from 2000. The NDRS dataset is estimated to comprise >60% of NHS MMR analyses performed since inception of NHS MMR analysis, with complete national data for full-gene analyses for 2016 onwards. Out of 9649 full-gene tests, 2724 had an abnormal result, approximately 70% of which were (likely) pathogenic. Data linkage to the National Cancer Registry demonstrated colorectal cancer was the most frequent cancer type in which full-gene analysis was performed. CONCLUSION: The NDRS MMR dataset is a unique national pan-laboratory amalgamation of individual-level clinical and genomic patient data with pseudonymised identifiers enabling linkage to other national datasets. This growing resource will enable longitudinal research and can form the basis of a live national genomic disease registry.
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Neoplasias , Medicina Estatal , Humanos , Reparo de Erro de Pareamento de DNA/genética , Laboratórios , GenômicaRESUMO
Germline pathogenic variants (GPVs) in the cancer predisposition genes BRCA1, BRCA2, MLH1, MSH2, MSH6, BRIP1, PALB2, RAD51D and RAD51C are identified in approximately 15% of patients with ovarian cancer (OC). While there are clear guidelines around clinical management of cancer risk in patients with GPV in BRCA1, BRCA2, MLH1, MSH2 and MSH6, there are few guidelines on how to manage the more moderate OC risk in patients with GPV in BRIP1, PALB2, RAD51D and RAD51C, with clinical questions about appropriateness and timing of risk-reducing gynaecological surgery. Furthermore, while recognition of RAD51C and RAD51D as OC predisposition genes has been established for several years, an association with breast cancer (BC) has only more recently been described and clinical management of this risk has been unclear. With expansion of genetic testing of these genes to all patients with non-mucinous OC, new data on BC risk and improved estimates of OC risk, the UK Cancer Genetics Group and CanGene-CanVar project convened a 2-day meeting to reach a national consensus on clinical management of BRIP1, PALB2, RAD51D and RAD51C carriers in clinical practice. In this paper, we present a summary of the processes used to reach and agree on a consensus, as well as the key recommendations from the meeting.
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Neoplasias da Mama , Proteínas de Ligação a DNA , Proteína do Grupo de Complementação N da Anemia de Fanconi , Predisposição Genética para Doença , Neoplasias Ovarianas , Feminino , Humanos , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Consenso , Proteínas de Ligação a DNA/genética , Proteína do Grupo de Complementação N da Anemia de Fanconi/genética , Predisposição Genética para Doença/genética , Células Germinativas/patologia , Mutação em Linhagem Germinativa/genética , Proteína 2 Homóloga a MutS/genética , Neoplasias Ovarianas/genética , Reino UnidoRESUMO
BACKGROUND: Germline genetic testing affords multiple opportunities for women with breast cancer, however, current UK NHS models for delivery of germline genetic testing are clinician-intensive and only a minority of breast cancer cases access testing. METHODS: We designed a rapid, digital pathway, supported by a genetics specialist hotline, for delivery of germline testing of BRCA1/BRCA2/PALB2 (BRCA-testing), integrated into routine UK NHS breast cancer care. We piloted the pathway, as part of the larger BRCA-DIRECT study, in 130 unselected patients with breast cancer and gathered preliminary data from a randomised comparison of delivery of pretest information digitally (fully digital pathway) or via telephone consultation with a genetics professional (partially digital pathway). RESULTS: Uptake of genetic testing was 98.4%, with good satisfaction reported for both the fully and partially digital pathways. Similar outcomes were observed in both arms regarding patient knowledge score and anxiety, with <5% of patients contacting the genetics specialist hotline. All progression criteria established for continuation of the study were met. CONCLUSION: Pilot data indicate preliminary demonstration of feasibility and acceptability of a fully digital pathway for BRCA-testing and support proceeding to a full powered study for evaluation of non-inferiority of the fully digital pathway, detailed quantitative assessment of outcomes and operational economic analyses. TRIAL REGISTRATION NUMBER: ISRCTN87845055.
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Neoplasias da Mama , Encaminhamento e Consulta , Humanos , Feminino , Medicina Estatal , Telefone , Testes Genéticos , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Reino UnidoRESUMO
PURPOSE: Variant classifications may change over time, driven by emergence of fresh or contradictory evidence or evolution in weighing or combination of evidence items. For variant classifications above the actionability threshold, which is classification of likely pathogenic or pathogenic, clinical actions may be irreversible, such as risk-reducing surgery or prenatal interventions. Variant reclassification up or down across the actionability threshold can therefore have significant clinical consequences. Laboratory approaches to variant reinterpretation and reclassification vary widely. METHODS: Cancer Variant Interpretation Group UK is a multidisciplinary network of clinical scientists and genetic clinicians from across the 24 Molecular Diagnostic Laboratories and Clinical Genetics Services of the United Kingdom (NHS) and Republic of Ireland. We undertook surveys, polls, and national meetings of Cancer Variant Interpretation Group UK to evaluate opinions about clinical and laboratory management regarding variant reclassification. RESULTS: We generated a consensus framework on variant reclassification applicable to cancer susceptibility genes and other clinical areas, which provides explicit recommendations for clinical and laboratory management of variant reclassification scenarios on the basis of the nature of the new evidence, the magnitude of evidence shift, and the final classification score. CONCLUSION: In this framework, clinical and laboratory resources are targeted for maximal clinical effect and minimal patient harm, as appropriate to all resource-constrained health care settings.
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Testes Genéticos , Neoplasias , Predisposição Genética para Doença , Variação Genética/genética , Humanos , Laboratórios , Neoplasias/diagnóstico , Neoplasias/genéticaRESUMO
PURPOSE: Conditions and thresholds applied for evidence weighting of within-codon concordance (PM5) for pathogenicity vary widely between laboratories and expert groups. Because of the sparseness of available clinical classifications, there is little evidence for variation in practice. METHODS: We used as a truthset 7541 dichotomous functional classifications of BRCA1 and MSH2, spanning 311 codons of BRCA1 and 918 codons of MSH2, generated from large-scale functional assays that have been shown to correlate excellently with clinical classifications. We assessed PM5 at 5 stringencies with incorporation of 8 in silico tools. For each analysis, we quantified a positive likelihood ratio (pLR, true positive rate/false positive rate), the predictive value of PM5-lookup in ClinVar compared with the functional truthset. RESULTS: pLR was 16.3 (10.6-24.9) for variants for which there was exactly 1 additional colocated deleterious variant on ClinVar, and the variant under examination was equally or more damaging when analyzed using BLOSUM62. pLR was 71.5 (37.8-135.3) for variants for which there were 2 or more colocated deleterious ClinVar variants, and the variant under examination was equally or more damaging than at least 1 colocated variant when analyzed using BLOSUM62. CONCLUSION: These analyses support the graded use of PM5, with potential to use it at higher evidence weighting where more stringent criteria are met.
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Variação Genética , Mutação de Sentido Incorreto , Proteína BRCA1/genética , Códon , Predisposição Genética para Doença , Variação Genética/genética , Humanos , Proteína 2 Homóloga a MutS/genética , Mutação de Sentido Incorreto/genéticaRESUMO
BACKGROUND: Neoadjuvant therapy reduces fitness, muscle mass, and quality of life (QOL). For patients undergoing chemotherapy and surgery for esophagogastric cancer, maintenance of fitness is paramount. This study investigated the effect of exercise and psychological prehabilitation on anaerobic threshold (AT) at cardiopulmonary exercise testing (CPET). Secondary endpoints included peak oxygen uptake (peak VO2), skeletal muscle mass, QOL, and neoadjuvant therapy completion. METHODS: This parallel-arm randomized controlled trial assigned patients with locally advanced esophagogastric cancer to receive prehabilitation or usual care. The 15-week program comprised twice-weekly supervised exercises, thrice-weekly home exercises, and psychological coaching. CPET was performed at baseline, 2 weeks after neoadjuvant therapy, and 1 week preoperatively. Skeletal muscle cross-sectional area at L3 was analyzed on staging and restaging computed tomography. QOL questionnaires were completed at baseline, mid-neoadjuvant therapy, at restaging laparoscopy, and postoperatively at 2 weeks, 6 weeks and 6 months. RESULTS: Fifty-four participants were randomized (prehabilitation group, n = 26; control group, n = 28). No difference in AT between groups was observed post-neoadjuvant therapy. Prehabilitation resulted in an attenuated peak VO2 decline {-0.4 [95% confidence interval (CI) -0.8 to 0.1] vs. -2.5 [95% CI -2.8 to -2.2] mL/kg/min; p = 0.022}, less muscle loss [-11.6 (95% CI -14.2 to -9.0) vs. -15.6 (95% CI -18.7 to -15.4) cm2/m2; p = 0.049], and improved QOL. More prehabilitation patients completed neoadjuvant therapy at full dose [prehabilitation group, 18 (75%) vs. control group, 13 (46%); p = 0.036]. No adverse events were reported. CONCLUSIONS: This study has demonstrated some retention of cardiopulmonary fitness (peak VO2), muscle, and QOL in prehabilitation subjects. Further large-scale trials will help determine whether these promising findings translate into improved clinical and oncological outcomes. Trial Registration ClinicalTrials.gov NCT02950324.
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Neoplasias Esofágicas , Neoplasias Gástricas , Neoplasias Esofágicas/terapia , Teste de Esforço , Terapia por Exercício , Humanos , Músculos , Terapia Neoadjuvante , Projetos Piloto , Cuidados Pré-Operatórios , Exercício Pré-Operatório , Qualidade de Vida , Neoplasias Gástricas/terapiaRESUMO
BACKGROUND: Several chronic inflammatory diseases co-exist with and accelerate sarcopenia (reduction in muscle strength, function and mass) and negatively impact on both morbidity and mortality. There is currently limited research on the extent of sarcopenia in such conditions, how to accurately assess it and whether there are generic or disease-specific mechanisms driving sarcopenia. Therefore, this study aims to identify potential mechanisms driving sarcopenia within chronic inflammatory disease via a multi-modal approach; in an attempt to help define potential interventions for future use. METHODS: This prospective cohort study will consist of a multi-modal assessment of sarcopenia and its underlying mechanisms. Recruitment will target three chronic inflammatory diseases: chronic liver disease (CLD) (n=50), with a subset of NAFLD (n=20), inflammatory bowel disease (IBD) (n=50) and rheumatoid arthritis (RA) (n=50) both before and after therapeutic intervention. In addition, 20 age and sex matched healthy individuals will be recruited for comparison. Participants will undergo 4 assessment visits at weeks 0, 2, 12 and 24. Visits will consist of the following assessments: blood tests, anthropometrics, functional assessment, quadriceps muscle imaging, actigraphy, quality of life questionnaires, food diary collection and muscle biopsy of the vastus lateralis (at weeks 2 and 24 only). In addition, stool and urine samples will be collected for future microbiome and metabolomics analysis. DISCUSSION: This is the first study to use a multi-modal assessment model to phenotype sarcopenia in these chronic inflammatory diseases. We hope to identify generic as well as disease-specific mechanisms driving sarcopenia. We appreciate that these cohorts do require separate standards of care treatments which limit comparison between groups. ETHICS AND DISSEMINATION: The study is approved by the Health Research Authority - West Midlands Solihull Research Ethics Service Committee Authority (REC reference: 18/WM/0167). Recruitment commenced in January 2019 and will continue until July 2021. The study was halted in March 2020 and again in January 2021 with the COVID-19 pandemic. The findings will be disseminated through peer-reviewed publications and conference presentations. All data will be stored on a secure server. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04734496.
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Doença Hepática Terminal/complicações , Sarcopenia/etiologia , Adulto , Artrite Reumatoide/complicações , Estudos de Casos e Controles , Feminino , Humanos , Doenças Inflamatórias Intestinais/complicações , Masculino , Hepatopatia Gordurosa não Alcoólica/complicações , Estudos ProspectivosRESUMO
In vitro models of muscle aging are useful for understanding mechanisms of age-related muscle loss and aiding the development of targeted therapies. To investigate mechanisms of age-related muscle loss in vitro utilizing ex vivo human serum, fasted blood samples were obtained from four old (72 ± 1 yr) and four young (26 ± 3 yr) men. Older individuals had elevated levels of plasma CRP, IL-6, HOMA-IR, and lower concentric peak torque and work-per-repetition compared with young participants (P < 0.05). C2C12 myotubes were serum and amino acid starved for 1 h and conditioned with human serum (10%) for 4 h or 24 h. After 4 h, C2C12 cells were treated with 5 mM leucine for 30 min. Muscle protein synthesis (MPS) was determined through the surface sensing of translation (SUnSET) technique and regulatory signaling pathways were measured via Western blot. Myotube diameter was significantly reduced in myotubes treated with serum from old, in comparison to young donors (84%, P < 0.001). MPS was reduced in myotubes treated with old donor serum, compared with young serum before leucine treatment (32%, P < 0.01). MPS and the phosphorylation of Akt, p70S6K, and eEF2 were increased in myotubes treated with young serum in response to leucine treatment, with a blunted response identified in cells treated with old serum (P < 0.05). Muscle protein breakdown signaling pathways did not differ between groups. In summary, we show that myotubes conditioned with serum from older individuals had decreased myotube diameter and MPS compared with younger individuals, potentially driven by low-grade systemic inflammation.
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Envelhecimento/genética , Meios de Cultura/farmacologia , Fibras Musculares Esqueléticas/efeitos dos fármacos , Proteínas Musculares/genética , Biossíntese de Proteínas/efeitos dos fármacos , Adulto , Idoso , Envelhecimento/metabolismo , Animais , Proteína C-Reativa/genética , Proteína C-Reativa/metabolismo , Linhagem Celular , Meios de Cultura/química , Humanos , Resistência à Insulina , Interleucina-6/sangue , Interleucina-6/genética , Leucina/farmacologia , Masculino , Camundongos , Modelos Biológicos , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/patologia , Proteínas Musculares/biossíntese , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Atrofia Muscular/genética , Atrofia Muscular/metabolismo , Atrofia Muscular/patologia , Fator 2 de Elongação de Peptídeos/genética , Fator 2 de Elongação de Peptídeos/metabolismo , Proteólise , Proteínas Proto-Oncogênicas c-akt/biossíntese , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Quinases S6 Ribossômicas 70-kDa/genética , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Transdução de SinaisRESUMO
INTRODUCTION: Sarcopenia is present in many chronic disease states including decompensated end stage liver disease (ESLD) and non-cirrhotic non-alcoholic fatty liver disease (NAFLD). Sarcopenia in ESLD can negatively impact quality of life and increase mortality. Despite this, very little is understood about the mechanisms of sarcopenia in these conditions. One key reason for this is the reluctance to undertake percutaneous muscle biopsies due to the perceived increased risks. ESLD can induce thrombocytopaenia and coagulopathy which significantly increases the risk of bleeding. In addition, patients with either NAFLD or ESLD often have co-morbidities that would require additional care and risk assessment. Thus, the aim of this study was to establish an effective and safe protocol for the implementation of percutaneous muscle biopsies in patients with NAFLD and ESLD. METHODS: A total of 47 patients with ESLD and 9 patients with non-cirrhotic NAFLD were recruited from the Liver Unit, Queen Elizabeth Hospital (Birmingham, United Kingdom). A total of 71 percutaneous vastus lateralis biopsies were attempted over two study visits. A vigorous safety screening occurred prior to and during each visit and a strict protocol was followed to mitigate against complications and risk. RESULTS: A total of 85% of patients consented to the muscle biopsy at either visit (48/56). A total of 9% of consented biopsies could not occur due to medical considerations, including high international normalised ratio (INR) (n = 3) and the use of aspirin (n = 4). Muscle tissue was obtained from 90% of attempts, with a mean average yield (wet weight tissue) of 98.1 ± 52.9 mg. CONCLUSION: Percutaneous muscle biopsies are both feasible and yield sufficient tissue in an ESLD population. The procedure is effective for obtaining muscle tissue whilst also safe, with only one adverse event. This study provides evidence for the successful use of muscle biopsies in this population, even in consideration of disease specific complications, medications, and comorbidities.
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BACKGROUND: Shockwave therapy (SWT) is a commonly used intervention for a number of musculoskeletal conditions with varying clinical outcomes. However, the capacity of SWT to influence pathophysiological processes and the morphology of affected tissues remains unclear. The objective of the current review is to evaluate changes in imaging outcomes of musculoskeletal conditions following SWT. METHODS: A comprehensive search of Medline, Embase, Cochrane Controlled Trials Register, CINAHL and SportDiscus was conducted from inception to October 2018. Prospective clinical trials evaluating the effectiveness of SWT based on changes in imaging outcomes were eligible for inclusion. Articles were evaluated independently for risk of bias using the Cochrane Risk of Bias list and the Methodological Index for Non-Randomized Studies. Random-effects meta-analysis and meta-regression with a priori determined covariates was conducted for each condition to determine potential predictors of SWT effects. RESULTS: Sixty-three studies were included, with data from 27 studies available for effect size pooling. Meta-analyses and meta-regression on imaging outcomes were performed for rotator cuff calcific tendinitis (n = 11), plantar fasciitis (n = 7) and osteonecrosis of the femoral head (n = 9). There was an overall reduction in the size of measured lesion following SWT (MD 8.44 mm (95%CI -4.30, 12.57), p < 0.001) for calcium deposit diameter, (MD 0.92 mm (95%CI -0.03, 1.81), p = 0.04) for plantar fascia thickness and (MD 4.84% (95%CI -0.06, 9.75), p = 0.05) for lesion size in femoral head osteonecrosis. Meta-regression showed no influence of SWT dosage parameters, however, baseline lesion size was an independent predictor for changes in imaging outcomes. CONCLUSIONS: SWT altered the morphology of musculoskeletal conditions, potentially reflecting changes in underlying pathophysiological processes. The parameters of SWT dosage are not significant predictors of changes in imaging outcomes. Lack of adequate reporting of imaging outcomes limited the conclusions that could be drawn from the current review. Registration number: PROSPERO CRD42018091140.
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Calcinose/terapia , Diagnóstico por Imagem/estatística & dados numéricos , Tratamento por Ondas de Choque Extracorpóreas/métodos , Doenças Musculoesqueléticas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Calcinose/diagnóstico por imagem , Ensaios Clínicos como Assunto , Diagnóstico por Imagem/métodos , Fasciíte Plantar/terapia , Feminino , Necrose da Cabeça do Fêmur/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Musculoesqueléticas/diagnóstico por imagem , Doenças Musculoesqueléticas/fisiopatologia , Avaliação de Resultados em Cuidados de Saúde , Estudos Prospectivos , Lesões do Manguito Rotador/patologiaRESUMO
INTRODUCTION: Neoadjuvant therapy prior to oesophagogastric resection is the gold standard of care for patients with T2 and/or nodal disease. Despite this, studies have taught us that chemotherapy decreases patients' functional capacity as assessed by cardiopulmonary exercise (CPX) testing. We aim to show that a multimodal prehabilitation programme, comprising supervised exercise, psychological coaching and nutritional support, will physically, psychologically and metabolically optimise these patients prior to oesophagogastric cancer surgery so they may better withstand the immense physical and metabolic stress placed on them by radical curative major surgery. METHODS AND ANALYSIS: This will be a prospective, randomised, controlled, parallel, single-centre superiority trial comparing a multimodal 'prehabilitation' intervention with 'standard care' in patients with oesophagogastric malignancy who are treated with neoadjuvant therapy prior to surgical resection. The primary aim is to demonstrate an improvement in baseline cardiopulmonary function as assessed by anaerobic threshold during CPX testing in an interventional (prehab) group following a 15-week preoperative exercise programme, throughout and following neoadjuvant treatment, when compared with those that undergo standard care (control group). Secondary objectives include changes in peak oxygen uptake and work rate (total watts achieved) at CPX testing, insulin resistance, quality of life, chemotherapy-related toxicity and completion, nutritional assessment, postoperative complication rate, length of stay and overall mortality. ETHICS AND DISSEMINATION: This study has been approved by the London-Bromley Research Ethics Committee and registered on ClinicalTrials.gov. The results will be disseminated in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT02950324; Pre-results.
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Neoplasias Esofágicas/reabilitação , Neoplasias Esofágicas/cirurgia , Terapia por Exercício/métodos , Terapia Neoadjuvante/métodos , Aptidão Física/fisiologia , Adulto , Idoso , Anastomose Cirúrgica/métodos , Quimiorradioterapia/métodos , Intervalo Livre de Doença , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Esofagectomia/métodos , Junção Esofagogástrica/patologia , Junção Esofagogástrica/cirurgia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios/métodos , Estudos Prospectivos , Medição de Risco , Estatísticas não Paramétricas , Análise de Sobrevida , Centros de Atenção Terciária , Reino UnidoRESUMO
Once considered an incurable disease, the continuous evolution of technologies and techniques has improved both oncological outcomes and quality of life for patients with rectal cancer. Multiport laparoscopic surgery for rectal cancer is the standard of care in many institutions and countries and is the approach that has been most subjected to controlled trial. Following a number of randomized trials as well as large series and registry reports and several Cochrane reviews, there is no evidence of any oncological disadvantage to laparoscopic surgery compared with the open approach and there is good evidence of improved short-term outcomes and some evidence of improved long-term outcomes. We describe the "standard" approach to multiport, laparoscopic low anterior resection.