Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 58
Filtrar
1.
Anal Chem ; 95(47): 17170-17176, 2023 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-37967208

RESUMO

Urinary volatolomics offers a noninvasive approach for disease detection and monitoring. Herein we present an improved methodology for global volatolomic profiling. Wide coverage was achieved by utilizing a multiphase sorbent for volatile organic compound (VOC) extraction. A single, midpolar column gas chromatography (GC) assay yielded substantially higher numbers of monitored VOCs compared to our previously reported single-sorbent method. Multidimensional GC (GC×GC) enhanced further biomarker discovery while data analysis was simplified by using a tile-based approach. At the same time, the required urine volume was reduced 5-fold from 2 to 0.4 mL. The applicability of the methodology was demonstrated in a pancreatic ductal adenocarcinoma cohort where previous findings were confirmed while a series of additional VOCs with diagnostic potential were discovered.


Assuntos
Compostos Orgânicos Voláteis , Humanos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Cromatografia Gasosa , Compostos Orgânicos Voláteis/análise
2.
Cancers (Basel) ; 15(10)2023 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-37345006

RESUMO

OBJECTIVE: Oesophagogastric cancer is the fifth most common cancer worldwide, with poor survival outcomes. The role of bacteria in the pathogenesis of oesophagogastric cancer remains poorly understood. DESIGN: A systematic search identified studies assessing the oesophagogastric cancer microbiome. The primary outcome was to identify bacterial enrichment specific to oesophagogastric cancer. Secondary outcomes included appraisal of the methodology, diagnostic performance of cancer bacteria and the relationship between oral and tissue microbiome. RESULTS: A total of 9295 articles were identified, and 87 studies were selected for analysis. Five genera were enriched in gastric cancer: Lactobacillus, Streptococcus, Prevotella, Fusobacterium and Veillonella. No clear trends were observed in oesophageal adenocarcinoma. Streptococcus, Prevotella and Fusobacterium were abundant in oesophageal squamous cell carcinoma. Functional analysis supports the role of immune cells, localised inflammation and cancer-specific pathways mediating carcinogenesis. STORMS reporting assessment identified experimental deficiencies, considering batch effects and sources of contamination prevalent in low-biomass samples. CONCLUSIONS: Functional analysis of cancer pathways can infer tumorigenesis within the cancer-microbe-immune axis. There is evidence that study design, experimental protocols and analytical techniques could be improved to achieve more accurate and representative results. Whole-genome sequencing is recommended to identify key metabolic and functional capabilities of candidate bacteria biomarkers.

3.
Anal Chem ; 95(2): 758-765, 2023 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-36602225

RESUMO

Volatolomics offers an opportunity for noninvasive detection and monitoring of human disease. While gas chromatography-mass spectrometry (GC-MS) remains the technique of choice for analyzing volatile organic compounds (VOCs), barriers to wider adoption in clinical practice still exist, including: sample preparation and introduction techniques, VOC extraction, throughput, volatolome coverage, biological interpretation, and quality control (QC). Therefore, we developed a complete pipeline for untargeted urinary volatolomic profiling. We optimized a novel extraction technique using HiSorb sorptive extraction, which exhibited high analytical performance and throughput. We achieved a broader VOC coverage by using HiSorb coupled with a set of complementary chromatographic methods and time-of-flight mass spectrometry. Furthermore, we developed a data preprocessing strategy by evaluating internal standard normalization, batch correction, and we adopted strict QC measures including removal of nonlinearly responding, irreproducible, or contaminated metabolic features, ensuring the acquisition of high-quality data. The applicability of this pipeline was evaluated in a clinical cohort consisting of pancreatic ductal adenocarcinoma (PDAC) patients (n = 28) and controls (n = 33), identifying four urinary candidate biomarkers (2-pentanone, hexanal, 3-hexanone, and p-cymene), which can successfully discriminate the cancer and noncancer subjects. This study presents an optimized, high-throughput, and quality-controlled pipeline for untargeted urinary volatolomic profiling. Use of the pipeline to discriminate PDAC from control subjects provides proof of principal of its clinical utility and potential for application in future biomarker discovery studies.


Assuntos
Compostos Orgânicos Voláteis , Humanos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Compostos Orgânicos Voláteis/análise , Espectrometria de Massas , Biomarcadores
4.
Dis Esophagus ; 36(2)2023 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-35795994

RESUMO

Prehabilitation aims to optimize a patient's functional capacity in preparation for surgery. Esophageal cancer patients have a high incidence of sarcopenia and commonly undergo neoadjuvant therapy, which is associated with loss of muscle mass. This study examines the effects of prehabilitation on body composition during neoadjuvant therapy in esophageal cancer patients. In this cohort study, changes in body composition were compared between esophageal cancer patients who participated in prehabilitation during neoadjuvant therapy and controls who did not receive prehabilitation. Assessment of body composition was performed from CT images acquired at the time of diagnosis and after neoadjuvant therapy. Fifty-one prehabilitation patients and 28 control patients were identified. There was a significantly greater fall in skeletal muscle index (SMI) in the control group compared with the prehabilitation patients (Δ SMI mean difference = -2.2 cm2/m2, 95% CI -4.3 to -0.1, p=0.038). Within the prehabilitation cohort, there was a smaller decline in SMI in patients with ≥75% adherence to exercise in comparison to those with lower adherence (Δ SMI mean difference = -3.2, 95% CI -6.0 to -0.5, P = 0.023). A greater decrease in visceral adipose tissue (VAT) was seen with increasing volumes of exercise completed during prehabilitation (P = 0.046). Loss of VAT during neoadjuvant therapy was associated with a lower risk of post-operative complications (P = 0.017). By limiting the fall in SMI and promoting VAT loss, prehabilitation may have multiple beneficial effects in patients with esophageal cancer. Multi-center, randomized studies are needed to further explore these findings.


Assuntos
Neoplasias Esofágicas , Exercício Pré-Operatório , Humanos , Estudos de Coortes , Terapia Combinada , Neoplasias Esofágicas/cirurgia , Neoplasias Esofágicas/complicações , Composição Corporal
6.
Ann Surg Oncol ; 29(9): 5689-5697, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35616747

RESUMO

BACKGROUND: Malnutrition commonly affects patients with esophageal cancer and has the potential to negatively influence treatment outcomes. The aim of this study was to investigate the impact of early (preoperative) jejunostomy tube feeding (JTF) in nutritionally 'high risk' patients receiving multimodal therapy for esophageal cancer. METHODS: Patients were selected to undergo early JTF during neoadjuvant chemoradiotherapy (nCRT) in accordance with European Society for Clinical Nutrition and Metabolism (ESPEN) and Enhanced Recovery after Surgery (ERAS®) Society guidelines. Clinical outcomes were compared with patients who received routine JTF from the time of esophagectomy. Body composition was determined from computed tomography (CT) images acquired at diagnosis, after nCRT, and ≥ 3 months after surgery. RESULTS: In total, 81 patients received early JTF and 91 patients received routine JTF. Patients who received early JTF had lower body mass index (BMI; 26.1 ± 4.6 vs. 28.4 ± 4.9; p = 0.002), greater weight loss, and worse performance status at diagnosis. Groups were otherwise well-matched for baseline characteristics. Rate of re-intubation (8.8% vs. 1.1%; p = 0.027), pulmonary embolism (5.0% vs. 0.0%; p = 0.046), and 90-day mortality (10.0% vs. 1.1%; p = 0.010) were worse in the early JTF group; however, overall survival was equivalent for both the early and routine JTF groups (p = 0.053). Wide variation in the degree of preoperative muscle loss and total adipose tissue loss was observed across the entire study cohort. Relative preoperative muscle and adipose tissue loss in patients with early and routine JTF was equivalent. CONCLUSIONS: In patients determined to be at 'high risk' of malnutrition, early JTF may prevent excess morbidity after esophagectomy with an associated relative preservation of parameters of body composition.


Assuntos
Neoplasias Esofágicas , Desnutrição , Composição Corporal , Nutrição Enteral/efeitos adversos , Nutrição Enteral/métodos , Neoplasias Esofágicas/cirurgia , Esofagectomia/efeitos adversos , Esofagectomia/métodos , Humanos , Jejunostomia/efeitos adversos , Jejunostomia/métodos , Desnutrição/etiologia , Terapia Neoadjuvante/métodos , Estudos Retrospectivos , Resultado do Tratamento , Redução de Peso
7.
Br J Surg ; 109(5): 418-425, 2022 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-35233634

RESUMO

BACKGROUND: Oesophageal adenocarcinoma poses a significant global health burden, yet the staging used to predict survival has limited ability to stratify patients by outcome. This study aimed to identify published clinical models that predict survival in oesophageal adenocarcinoma and to evaluate them using an independent international multicentre dataset. METHODS: A systematic literature search (title and abstract) using the Ovid Embase and MEDLINE databases (from 1947 to 11 July 2020) was performed. Inclusion criteria were studies that developed or validated a clinical prognostication model to predict either overall or disease-specific survival in patients with oesophageal adenocarcinoma undergoing surgical treatment with curative intent. Published models were validated using an independent dataset of 2450 patients who underwent oesophagectomy for oesophageal adenocarcinoma with curative intent. RESULTS: Seventeen articles were eligible for inclusion in the study. Eleven models were suitable for testing in the independent validation dataset and nine of these were able to stratify patients successfully into groups with significantly different survival outcomes. Area under the receiver operating characteristic curves for individual survival prediction models ranged from 0.658 to 0.705, suggesting poor-to-fair accuracy. CONCLUSION: This study highlights the need to concentrate on robust methodologies and improved, independent, validation, to increase the likelihood of clinical adoption of survival predictions models.


Assuntos
Adenocarcinoma , Neoplasias Esofágicas , Bases de Dados Factuais , Esofagectomia/métodos , Humanos , Prognóstico
8.
Ann Surg ; 275(1): 121-130, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-32224728

RESUMO

OBJECTIVE: The aim was to develop a reliable surgical quality assurance system for 2-stage esophagectomy. This development was conducted during the pilot phase of the multicenter ROMIO trial, collaborating with international experts. SUMMARY OF BACKGROUND DATA: There is evidence that the quality of surgical performance in randomized controlled trials influences clinical outcomes, quality of lymphadenectomy and loco-regional recurrence. METHODS: Standardization of 2-stage esophagectomy was based on structured observations, semi-structured interviews, hierarchical task analysis, and a Delphi consensus process. This standardization provided the structure for the operation manual and video and photographic assessment tools. Reliability was examined using generalizability theory. RESULTS: Hierarchical task analysis for 2-stage esophagectomy comprised fifty-four steps. Consensus (75%) agreement was reached on thirty-nine steps, whereas fifteen steps had a majority decision. An operation manual and record were created. A thirty five-item video assessment tool was developed that assessed the process (safety and efficiency) and quality of the end product (anatomy exposed and lymphadenectomy performed) of the operation. The quality of the end product section was used as a twenty seven-item photographic assessment tool. Thirty-one videos and fifty-three photographic series were submitted from the ROMIO pilot phase for assessment. The overall G-coefficient for the video assessment tool was 0.744, and for the photographic assessment tool was 0.700. CONCLUSIONS: A reliable surgical quality assurance system for 2-stage esophagectomy has been developed for surgical oncology randomized controlled trials. ETHICAL APPROVAL: 11/NW/0895 and confirmed locally as appropriate, 12/SW/0161, 16/SW/0098.Trial registration number: ISRCTN59036820, ISRCTN10386621.


Assuntos
Neoplasias Esofágicas/cirurgia , Esofagectomia/métodos , Esofagectomia/normas , Procedimentos Cirúrgicos Minimamente Invasivos/normas , Garantia da Qualidade dos Cuidados de Saúde/organização & administração , Ensaios Clínicos Controlados Aleatórios como Assunto , Técnica Delphi , Humanos , Excisão de Linfonodo , Fotografação , Projetos Piloto , Complicações Pós-Operatórias , Garantia da Qualidade dos Cuidados de Saúde/métodos , Gravação em Vídeo
9.
Ann Surg ; 275(1): e140-e147, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-32068555

RESUMO

OBJECTIVE: The aim of this study was to investigate long-term HRQOL and symptom evolution in disease free patients up to 20 years after esophagectomy. BACKGROUND: Esophagectomy has been associated with decreased HRQOL and persistent gastrointestinal symptoms. METHODS: The study cohort was identified from 2 high volume centers for the management of esophageal cancer. Patients completed HRQOL and symptom questionnaires, including: Digestive Symptom Questionnaire, EORTC QLQ-C30, EORTC QLQ-OG25 Euro QoL 5D, and SF36. Patients were assessed in 3 cohorts: <1 year; 1-5 years, and; >5 years after surgery. RESULTS: In total 171 of 222 patients who underwent esophagectomy between 1991 and 2017 who met inclusion criteria and were contactable, responded to the questionnaires, corresponding to a response rate of 77%. Median age was 66.2 years, and median time from operation to survey was 5.6 years (range 0.3-23.1). Early satiety was the most commonly reported symptom in all patients irrespective of timeframe (87.4%; range 82%-92%). Dysphagia was seen to decrease over time (58% at <2 years; 28% at 2-5 years; 20% at >5 years; P = 0.013). Weight loss scores demonstrated nonstatistical improvement over time. All other symptom scores including heartburn, regurgitation, respiratory symptoms, and pain scores remained constant over time. Average HRQOL did not improve from levels 1 year after surgery compared to patients up to 23 years after esophagectomy. CONCLUSION: With the exception of dysphagia, which improved over time, esophagectomy was associated with decreased HRQOL and lasting gastrointestinal symptoms up to 20 years after surgery. Pertinently however long-term survivors after oesophagectomy demonstrated comparable to improved HRQOL compared to the general population. The impact of esophagectomy on gastrointestinal symptoms and long-term HRQOL should be considered when counseling and caring for patients undergoing esophagectomy.


Assuntos
Neoplasias Esofágicas/cirurgia , Esofagectomia , Junção Esofagogástrica/cirurgia , Qualidade de Vida , Idoso , Intervalo Livre de Doença , Neoplasias Esofágicas/mortalidade , Feminino , Seguimentos , Previsões , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida/tendências , Sobreviventes , Reino Unido/epidemiologia , Estados Unidos/epidemiologia
10.
Acta Clin Belg ; 77(2): 368-376, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33586631

RESUMO

INTRODUCTION: We present the results of the COVID-19 rule-out protocol at Ghent University Hospital, a step-wise testing approach which included repeat NFS SARS-CoV-2 rRT-PCR, respiratory multiplex RT-PCR, low-dose chest CT and bronchoscopy with BAL to confirm or rule-out SARS-CoV-2 infection in patients admitted with symptoms suggestive of COVID-19. RESULTS: Between 19 March 2020 and 30 April 2020, 455 non-critically ill patients with symptoms suspect for COVID-19 were admitted. The initial NFS for SARS-CoV-2 rRT-PCR yielded 66.9%, the second NFS 25.4% and bronchoscopy with BAL 5.9% of total COVID-19 diagnoses. In the BAL fluid, other respiratory pathogens were detected in 65% (13/20) of the COVID-19 negative patients and only in 1/7 COVID-19 positive patients. Retrospective antibody testing at the time around BAL sampling showed a positive IgA or IgG in 42.9 % of the COVID-19 positive and 10.5% of the COVID-19 negative group. Follow-up serology showed 100% COVID-19 positivity in the COVID-19 positive group and 100% IgG negativity in the COVID-19 negative group. CONCLUSION: In our experience, bronchoscopy with BAL can have an added value to rule-in or rule-out COVID-19 in patients with clinical and radiographical high-likelihood of COVID-19 and repeated negative NFS testing. Furthermore, culture and respiratory multiplex PCR on BAL fluid can aid to identify alternative microbial etiological agents in this group. Retrospective analysis of antibody development in this selected group of patients suggests that the implementation of serological assays in the routine testing protocol will decrease the need for invasive procedures like bronchoscopy.


Assuntos
COVID-19 , Broncoscopia , COVID-19/diagnóstico , Humanos , Estudos Retrospectivos , SARS-CoV-2 , Tomografia Computadorizada por Raios X
11.
BMJ Open ; 11(10): e045546, 2021 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-34620652

RESUMO

INTRODUCTION: Three-dimensional (3D) reconstruction describes the generation of either virtual or physically printed anatomically accurate 3D models from two-dimensional medical images. Their implementation has revolutionised medical practice. Within surgery, key applications include growing roles in operative planning and procedures, surgical education and training, as well as patient engagement and education. In comparison to other surgical specialties, oesophagogastric surgery has been slow in their adoption of this technology. Herein the authors outline a scoping review protocol that aims to analyse the current role of 3D modelling in oesophagogastric surgery and highlight any unexplored avenues for future research. METHODS AND ANALYSIS: The protocol was generated using internationally accepted methodological frameworks. A succinct primary question was devised, and a comprehensive search strategy was developed for key databases (MEDLINE, Embase, Elsevier Scopus and ISI Web of Science). These were searched from their inception to 1 June 2020. Reference lists will be reviewed by hand and grey literature identified using OpenGrey and Grey Literature Report. The protocol was registered to the Open Science Framework (osf.io/ta789).Two independent reviewers will screen titles, abstracts and perform full-text reviews for study selection. There will be no methodological quality assessment to ensure a full thematic analysis is possible. A data charting tool will be created by the investigatory team. Results will be analysed to generate descriptive numerical tabular results and a thematic analysis will be performed. ETHICS AND DISSEMINATION: Ethical approval was not required for the collection and analysis of the published data. The scoping review report will be disseminated through a peer-reviewed publication and international conferences. REGISTRATION DETAILS: The scoping review protocol has been registered on the Open Science Framework (https://osf.io/ta789).


Assuntos
Atenção à Saúde , Revisão por Pares , Humanos , Projetos de Pesquisa , Literatura de Revisão como Assunto
12.
BMC Palliat Care ; 20(1): 131, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34433457

RESUMO

BACKGROUND: To be able to provide high-quality palliative care, there need to be a number of organizational structures available in the nursing homes. It is unclear to what extent such structures are actually present in nursing homes in Europe. We aim to examine structural indicators for quality of palliative care in nursing homes in Europe and to evaluate the differences in terms of availability of and access to palliative care, infrastructure for residents and families, multidisciplinary meetings and quality improvement initiatives. METHODS: A PACE cross-sectional study (2015) of nursing homes in Belgium, England, Finland, Italy, the Netherlands and Poland. Nursing homes (N = 322) were selected in each country via proportional stratified random sampling. Nursing home administrators (N = 305) filled in structured questionnaires on nursing home characteristics. Organization of palliative care was measured using 13 of the previously defined IMPACT structural indicators for quality of palliative care covering four domains: availability of and access to palliative care, infrastructure for residents and families, multidisciplinary meetings and quality improvement initiatives. We calculated structural indicator scores for each country and computed differences in indicator scores between the six countries. Pearson's Chi-square test was used to compute the p-value of each difference. RESULTS: The availability of specialist palliative care teams in nursing homes was limited (6.1-48.7%). In Finland, Poland and Italy, specialist advice was also less often available (35.6-46.9%). Up to 49% of the nursing homes did not provide a dedicated contact person who maintained regular contact with the resident and relatives. The 24/7 availability of opioids for all nursing home residents was low in Poland (37.5%). CONCLUSIONS: This study found a large heterogeneity between countries in the organization of palliative care in nursing homes, although a common challenge is ensuring sufficient structural access to specialist palliative care services. Policymakers and health and palliative care organizations can use these structural indicators to identify areas for improvement in the organization of palliative care.


Assuntos
Enfermagem de Cuidados Paliativos na Terminalidade da Vida , Cuidados Paliativos , Estudos Transversais , Europa (Continente) , Humanos , Casas de Saúde
13.
BMJ Open ; 11(4): e044691, 2021 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-33849851

RESUMO

OBJECTIVES: To examine the feasibility and acceptability of breath research in primary care. DESIGN: Non-randomised, prospective, mixed-methods cross-sectional observational study. SETTING: Twenty-six urban primary care practices. PARTICIPANTS: 1002 patients aged 18-90 years with gastrointestinal symptoms. MAIN OUTCOME MEASURES: During the first 6 months of the study (phase 1), feasibility of patient enrolment using face-to-face, telephone or SMS-messaging (Short Message Service) enrolment strategies, as well as processes for breath testing at local primary care practices, were evaluated. A mixed-method iterative study design was adopted and outcomes evaluated using weekly Plan-Do-Study-Act cycles, focus groups and general practitioner (GP) questionnaires.During the second 6 months of the study (phase 2), patient and GP acceptability of the breath test and testing process was assessed using questionnaires. In addition a 'single practice' recruitment model was compared with a 'hub and spoke' centralised recruitment model with regards to enrolment ability and patient acceptability.Throughout the study feasibility of the collection of a large number of breath samples by clinical staff over multiple study sites was evaluated and quantified by the analysis of these samples using mass spectrometry. RESULTS: 1002 patients were recruited within 192 sampling days. Both 'single practice' and 'hub and spoke' recruitment models were effective with an average of 5.3 and 4.3 patients accrued per day, respectively. The 'hub and spoke' model with SMS messaging was the most efficient combined method of patient accrual. Acceptability of the test was high among both patients and GPs. The methodology for collection, handling and analysis of breath samples was effective, with 95% of samples meeting quality criteria. CONCLUSIONS: Large-scale breath testing in primary care was feasible and acceptable. This study provides a practical framework to guide the design of Phase III trials examining the performance of breath testing in primary care.


Assuntos
Atenção Primária à Saúde , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Estudos de Viabilidade , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Inquéritos e Questionários , Adulto Jovem
14.
Dis Esophagus ; 34(11)2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33822916

RESUMO

This study seeks to define long-term variation in body composition in patients undergoing esophagectomy for cancer and to associate those changes with survival. Assessment of skeletal muscle, visceral (VAT) and subcutaneous adipose tissue (SAT) was performed using computed tomography (CT) images routinely acquired: at diagnosis; after neoadjuvant therapy, and; >6 months after esophagectomy. In cases where multiple CT scans were performed >6 months after surgery, all available images were assessed. Ninty-seven patients met inclusion criteria with a median of 2 (range 1-10) postoperative CT images acquired between 0.5 and 9.7 years after surgery. Following surgical treatment of esophageal cancer, patients lost on average 13.3% of their skeletal muscle, 64.5% of their VAT and 44.2% of their SAT. Sarcopenia at diagnosis was not associated with worse overall survival (66.3% vs. 68.5%; P = 0.331). Sarcopenia 1 year after esophagectomy was however associated with lower 5-year overall survival (53.8% vs. 87.5%; P = 0.019). Survival was lower in those patients who had >10% decrease in skeletal muscle index (SMI; 33.3% vs. 72.1%; P = 0.003) and >40% decrease in SAT 1 year after surgery (40.4% vs. 67.4%; P = 0.015). On multivariate analysis, a decline in SMI 1 year after surgery was predictive of worse survival (HR 0.38, 95%CI 0.20-0.73; P = 0.004). This study provides new insight relating to long-term variation in body composition in patients undergoing esophagectomy for cancer. Findings provide further evidence of the importance of body composition, in particular depletion of skeletal muscle, in predicting survival following esophagectomy.


Assuntos
Esofagectomia , Sarcopenia , Adiposidade , Esofagectomia/efeitos adversos , Humanos , Músculo Esquelético/diagnóstico por imagem , Prognóstico , Estudos Retrospectivos , Sarcopenia/diagnóstico por imagem , Sarcopenia/etiologia
15.
Nat Commun ; 12(1): 1454, 2021 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-33674602

RESUMO

Volatile aldehydes are enriched in esophageal adenocarcinoma (EAC) patients' breath and could improve early diagnosis, however the mechanisms of their production are unknown. Here, we show that weak aldehyde detoxification characterizes EAC, which is sufficient to cause endogenous aldehyde accumulation in vitro. Two aldehyde groups are significantly enriched in EAC biopsies and adjacent tissue: (i) short-chain alkanals, and (ii) medium-chain alkanals, including decanal. The short-chain alkanals form DNA-adducts, which demonstrates genotoxicity and confirms inadequate detoxification. Metformin, a putative aldehyde scavenger, reduces this toxicity. Tissue and breath concentrations of the medium-chain alkanal decanal are correlated, and increased decanal is linked to reduced ALDH3A2 expression, TP53 deletion, and adverse clinical features. Thus, we present a model for increased exhaled aldehydes based on endogenous accumulation from reduced detoxification, which also causes therapeutically actionable genotoxicity. These results support EAC early diagnosis trials using exhaled aldehyde analysis.


Assuntos
Adenocarcinoma/diagnóstico , Adenocarcinoma/metabolismo , Aldeídos/metabolismo , Aldeídos/toxicidade , Biomarcadores Tumorais , Dano ao DNA/efeitos dos fármacos , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/patologia , Aldeído Desidrogenase/metabolismo , Aldeído Oxirredutases/genética , Aldeído Oxirredutases/metabolismo , Adutos de DNA , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Esôfago , Genes p53/genética , Humanos , Metformina
16.
Eur J Surg Oncol ; 47(4): 748-756, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33059943

RESUMO

Where surgery forms the primary curative modality in surgical oncology trials the quality of this intervention has the potential to directly influence outcomes. Many trials however lack a robust framework to ensure surgical quality. We aim to report existing published challenges to quality assurance of surgical interventions within oncological trials. A systematic on-line literature search of Embase and Medline identified 34 relevant studies, including 19 RCTs, 11 further analyses of the primary RCTs, and 4 trial protocols. Inclusion criteria: oncological RCTs with a surgical intervention and/or associated publications relevant to the research question; 'Challenges to quality assurance of surgery in clinical oncology trials'. Selected articles were assessed by two reviewers to identify reported challenges to quality assurance of surgical intervention within these trials. Reported challenges to surgical quality could be classified as those affecting credentialing, standardisation and monitoring of surgical interventions. Constraints of using case volume for credentialing surgeons; inter-centre variation in the definition and execution of interventions; insufficient training, and monitoring of surgical quality, were the most commonly encountered challenges within each of these three domains. Findings confirmed an inadequacy in the implementation and reporting of effective surgical quality assurance measures. The surgical community should enable implementation of agreed upon mitigating strategies to overcome challenges to surgical quality in oncology trials.


Assuntos
Neoplasias/cirurgia , Garantia da Qualidade dos Cuidados de Saúde , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Procedimentos Cirúrgicos Operatórios/normas , Humanos
17.
Int J Surg Case Rep ; 75: 394-397, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32992096

RESUMO

INTRODUCTION: Acute lower gastrointestinal haemorrhage can potentially be life-threatening. We present a case of a massive rectal bleed which was managed successfully with a balloon tamponade device designed for upper gastrointestinal haemorrhage. PRESENTATION OF CASE: A 75-year-old gentleman, with a history of human immunodeficiency virus and cirrhosis with portal hypertension, presented with bright red rectal bleeding. Investigations showed a low haemoglobin level (74 g/L) and deranged clotting. Oesophago-gastro-duodenoscopy demonstrated no fresh or altered blood. Flexible sigmoidoscopy revealed active bleeding from a varix within the anterior rectal wall 4 cm from the anal verge. Efforts to stop the bleeding, including endoscopic clips, adrenaline injection and rectal packing, were unsuccessful and the patient became haemodynamically unstable. A Sengstaken-Blakemore tube was inserted per rectum and the gastric balloon was inflated to tamponade the lower rectum. The oesophageal balloon was then inflated to hold the gastric balloon firmly in place. A computed tomography angiogram demonstrated no evidence of haemorrhage with balloon tamponade. After 36 h, the balloon was removed with no further episodes of bleeding. DISCUSSION: The application of a balloon tamponade device should be considered in the management algorithm for acute lower gastrointestinal bleed. Advantages include its rapid insertion, immediate results and ability to measure further bleeding after the catheter has been placed. CONCLUSION: Sengstaken-Blakemore tube per rectum may effectively control massive low rectal bleeding when alternative methods have been unsuccessful.

18.
J Cachexia Sarcopenia Muscle ; 11(3): 756-767, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32096923

RESUMO

BACKGROUND: Influence of sarcopenia in combination with other body composition parameters and muscle strength on outcomes after oesophageal surgery for oesophageal cancer remains unclear. The objectives were (i) to describe the incidence of sarcopenia in relation to adipose tissue quantity and distribution and muscle strength; (ii) to evaluate if neoadjuvant chemoradiation (nCRTx) influences body composition and muscle strength; and (iii) to evaluate the influence of body composition and muscle strength on post-operative morbidity and long-term survival. METHODS: This retrospective study included patients with oesophageal cancer who received nCRTx followed by surgery between January 2011 and 2016. Skeletal muscle, visceral, and subcutaneous adipose tissue cross-sectional areas were calculated based on computed tomography scans, and muscle strength was measured using hand grip tests, 30 seconds chair stand tests, and maximal inspiratory and expiratory pressure tests prior to nCRTx and after nCRTx. RESULTS: A total of 322 patients were included in this study. Sarcopenia was present in 55.6% of the patients prior to nCRTx and in 58.2% after nCRTx (P = 0.082). Patients with sarcopenia had a significantly lower muscle strength and higher fat percentage. The muscle strength and incidence of sarcopenia increased while the mean body mass index and fat percentage decreased during nCRTx. A body mass index above 25 kg/m2 was associated with anastomotic leakage (P = 0.032). Other body composition parameters were not associated with post-operative morbidity. A lower handgrip strength prior to nCRTx was associated with pulmonary and cardiac complications (P = 0.023 and P = 0.009, respectively). In multivariable analysis, a lower number of stands during the 30 seconds chair stand test prior to nCRTx (hazard ratio 0.93, 95% confidence interval 0.87-0.99, P = 0.017) and visceral adipose tissue of >128 cm2 after nCRTx (hazard ratio 1.81, 95% confidence interval 1.30-2.53, P = 0.001) were associated with worse overall survival. CONCLUSIONS: Sarcopenia occurs frequently in patients with oesophageal cancer and is associated with less muscle strength and a higher fat percentage. Body composition changes during nCRTx did not influence survival. Impaired muscle strength and a high amount of visceral adipose tissue are associated with worse survival. Therefore, patients with poor fitness might benefit from preoperative nutritional and muscle strengthening guidance, aiming to increase muscle strength and decrease visceral adipose tissue. However, this should be confirmed in a large prospective study.


Assuntos
Neoplasias Esofágicas/terapia , Composição Corporal , Neoplasias Esofágicas/fisiopatologia , Feminino , Humanos , Pessoa de Meia-Idade , Força Muscular , Estudos Retrospectivos , Resultado do Tratamento
19.
J Laparoendosc Adv Surg Tech A ; 30(4): 358-362, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31990609

RESUMO

Background and Aims: Laparoscopic Heller's myotomy (LHM), per oral endoscopic myotomy, and pneumatic dilatation are well-established methods to treat achalasia. The ideal treatment algorithm in elderly patients is, however, still elusive. This multicenter study aims to evaluate outcomes and changes in routine therapeutic options in patients >80 years of age. Methods: Worldwide high-volume centers for the treatment of achalasia were surveyed. Therapeutic options and outcomes in patients >80 years of age were reviewed. Results: Eighty-five (54% men, mean age 84 ± 4 years) patients were studied. Primary treatment was endoscopic in 43 (51%) patients, surgical in 39 (46%) patients (30 LHM, 9 cardioplasty + gastrectomy), and medical in 3 (4%) patients. Four centers tailored treatment based on age (14% of the patients). Secondary treatment was necessary in 34 (40%) patients: 30 of them with endoscopic treatment as primary treatment. LHM was performed in 20 patients and endoscopic treatment in 14 patients. A total of 11 (13%) patients had complications after LHM. Seven had LHM or cardioplasty + gastrectomy as primary treatment. Four had LHM as secondary treatment. The mean time of hospitalization was 4 ± 2 days for those who did not have complications, and 7 ± 6 days for those who had complications. Conclusions: Most specialized centers do not tailor treatment based on advanced age. Treatment of the oldest-old patients should be based solely on their physiologic and mental health, not their age. Endoscopic treatment has a high rate of recurrence and gastrectomy a high rate of complications in his population. LHM seems to be a safe option with good outcomes in this population.


Assuntos
Acalasia Esofágica/cirurgia , Miotomia de Heller/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Fatores Etários , Idoso de 80 Anos ou mais , Dilatação , Feminino , Seguimentos , Pesquisas sobre Atenção à Saúde , Humanos , Laparoscopia/estatística & dados numéricos , Masculino , Seleção de Pacientes , Estudos Retrospectivos , Resultado do Tratamento
20.
Ann Thorac Surg ; 109(1): 233-240, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31479636

RESUMO

BACKGROUND: Sarcopenia may be an important predictive factor of outcomes after lung transplantation (LTx). Serum albumin and the 6-minute walk distance (6MWD) have been shown to be a marker of LTx outcomes. We measured sarcopenia, albumin, and 6MWD in a cohort of LTx patients and analyzed the utility of these as markers of outcomes for LTx patients. METHODS: We retrospectively identified LTx recipients from 2013-2018 at our institution who underwent computed tomographic imaging during their listing evaluation. From that image, we measured skeletal muscle cross-sectional surface area at the third lumbar vertebral level, and sarcopenia was diagnosed by established cutoffs. Associations between sarcopenia, albumin, 6MWD, and survival, and hospital length of stay, complications, readmissions, and discharge destination were evaluated. RESULTS: Sarcopenia was found in 72% (95 of 132) of patients, 18% (24 of 131) of patients were hypoalbuminemic, and 41% had a low 6MWD. Survival was not associated with presence of sarcopenia (hazard ratio [HR], 1.06; 95% confidence interval [CI], 0.46-2.42) or low 6MWD (HR, 0.86; 95% CI, 0.410-1.83). Hospital length of stay, complications, readmissions, and discharge destination were not influenced by sarcopenia or 6MWD. In contrast, hypoalbuminemia was independently associated with decreased survival (HR, 2.25; 95% CI, 1.04-4.85) and a higher grade of postoperative complications (P = .04). CONCLUSIONS: Sarcopenia is prevalent in LTx patients. Neither sarcopenia nor 6MWD predicted mortality or short-term outcomes after LTx. This is in contrast to albumin levels, which were inversely associated with survival and complications. Albumin shows promise as an important predictor of mortality and short-term outcomes after LTx.


Assuntos
Fragilidade/diagnóstico , Transplante de Pulmão , Feminino , Fragilidade/sangue , Fragilidade/complicações , Fragilidade/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Prognóstico , Estudos Retrospectivos , Sarcopenia/complicações , Albumina Sérica/análise , Resultado do Tratamento , Teste de Caminhada
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA