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Lung volume reduction surgery (LVRS) has been shown to be beneficial in patients with chronic obstructive pulmonary disease, but there is low uptake, partly due to perceived concerns of high operative mortality. We aimed to develop an individualised risk score following LVRS.This was a cohort study of patients undergoing LVRS. Factors independently predicting 90-day mortality and a risk prediction score were identified. Reliability of the score was tested using area under the receiver operating characteristic curve (AUROC).237 LVRS procedures were performed. The multivariate analysis factors associated independently with death were: body mass index (BMI)<18.5â kg·m-2 (OR 2.83, p=0.059), forced expiratory volume in 1â s (FEV1)<0.71â L (OR 5.47, p=0.011) and transfer factor of the lung for carbon monoxide (TLCO) <20% (OR 5.56, p=0.031). A risk score was calculated and total score assigned. AUROC for the risk score was 0.80 and a better predictor than individual components (p<0.01). The score was stratified into three risk groups. Of the total patients, 46% were classified as low risk. Similar improvements in lung function and health status were seen in all groups. The score was introduced and tested in a further 71 patients. AUROC for 90-day mortality in this cohort was 0.84.It is possible to provide an individualised predictive risk score for LVRS, which may aid decision making for both clinicians and patients.
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Pulmão/fisiopatologia , Pulmão/cirurgia , Pneumonectomia/métodos , Índice de Gravidade de Doença , Idoso , Área Sob a Curva , Índice de Massa Corporal , Monóxido de Carbono/química , Tomada de Decisões , Feminino , Volume Expiratório Forçado , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Pletismografia , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/mortalidade , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/cirurgia , Curva ROC , Análise de Regressão , Risco , Sensibilidade e Especificidade , Fatores de TempoRESUMO
PURPOSE OF REVIEW: To review the latest developments in surgery for malignant pleural mesothelioma both in patient selection, surgical technique, and strategy. RECENT FINDINGS: The International Association for the Study of Lung Cancer mesothelioma staging project has produced data to inform the 8th tumour node metastasis revision. The difficulty in clinical N staging and clinical T staging are highlighted and the importance of tumour volume is recognized. New imaging techniques can be utilized to assess tumour volume. The transition from extrapleural pneumonectomy to lung-sparing pleurectomy/decortication has extended the role of cancer-directed surgery into a more elderly population. More aggressive multimodality regimes, including induction radiotherapy are available to a selected population and adjuvant radiotherapy and chemotherapy are feasible in the elderly majority. Additional chemotherapy should not be delayed in those with poorer prognosis node positive, nonepithelioid disease. SUMMARY: Radical surgery for malignant pleural mesothelioma can achieve significant survival when targeted in those with the best prognosis by careful staging. It can be made more accessible by lung preservation without compromising outcome. It should be part of multimodality therapy.
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Neoplasias Pulmonares/patologia , Mesotelioma/cirurgia , Pleura/patologia , Neoplasias Pleurais/patologia , Pneumonectomia/métodos , Terapia Combinada , Humanos , Neoplasias Pulmonares/cirurgia , Mesotelioma Maligno , Estadiamento de Neoplasias , Seleção de Pacientes , Pleura/cirurgia , Neoplasias Pleurais/cirurgia , Radioterapia Adjuvante , Procedimentos Cirúrgicos Torácicos/métodos , Resultado do TratamentoRESUMO
INTRODUCTION: The incidental early-stage thymic mass presents a diagnostic challenge. Video-assisted thoracoscopic (VAT) thymectomy is an attractive but potentially morbid solution. The aim was to show it can be safely applied as a first-line modality in those with undiagnosed thymic enlargement with acceptable long-term results. METHODS: A total of 45 patients were identified (24 male, median age 52 interquartile range [IQR]: 41-66 years) in a 14-year experience who had CT evidence of an enlarged, possibly malignant thymic mass, but no tissue diagnosis before undertaking VAT thymectomy. The clinical outcomes of both benign and malignant diagnoses were compared. RESULTS: Myasthenic symptoms were present in 20 patients (44%), whereas 15 (33%) were asymptomatic. Benign lesions were resected in 27 patients (60%): thymic hyperplasia (56%), thymic cyst (33%), lipoma (7%) and xanthogranulomatous inflammation (4%). Of the 18 malignant patients, 82% had thymoma (three had Masaoka Stage I, 11 Stage II and one Stage III), 6% thymic carcinoma, 6% teratoma and 6% seminoma. Seven patients required radiotherapy for R1 resection. There was no difference in median hospital stay in either group: Benign group: 4 versus 5 days (P = 0.07). One patient in both groups required conversion to open. Two patients in the malignant group had significant morbidity (one myocardial infarction and one pulmonary embolism). There were no cases of tumour recurrence or mortality at a median follow-up of 6.6 years (IQR: 4.4-9.5 years). CONCLUSION: Right-sided diagnostic VAT thymectomy is a safe and effective first-line approach to suspected malignant thymic enlargement. At 5-year follow-up, there were no cases of recurrence in the malignant group.
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BACKGROUND: Malignant pleural mesothelioma incidence continues to rise, with few available evidence-based therapeutic options. Results of previous non-randomised studies suggested that video-assisted thoracoscopic partial pleurectomy (VAT-PP) might improve symptom control and survival. We aimed to compare efficacy in terms of overall survival, and cost, of VAT-PP and talc pleurodesis in patients with malignant pleural mesothelioma. METHODS: We undertook an open-label, parallel-group, randomised, controlled trial in patients aged 18 years or older with any subtype of confirmed or suspected mesothelioma with pleural effusion, recruited from 12 hospitals in the UK. Eligible patients were randomly assigned (1:1) to either VAT-PP or talc pleurodesis by computer-generated random numbers, stratified by European Organisation for Research and Treatment of Cancer risk category (high vs low). The primary outcome was overall survival at 1 year, analysed by intention to treat (all patients randomly assigned to a treatment group with a final diagnosis of mesothelioma). This trial is registered with ClinicalTrials.gov, number NCT00821860. FINDINGS: Between Oct 24, 2003, and Jan 24, 2012, we randomly assigned 196 patients, of whom 175 (88 assigned to talc pleurodesis, 87 assigned to VAT-PP) had confirmed mesothelioma. Overall survival at 1 year was 52% (95% CI 41-62) in the VAT-PP group and 57% (46-66) in the talc pleurodesis group (hazard ratio 1·04 [95% CI 0·76-1·42]; p=0·81). Surgical complications were significantly more common after VAT-PP than after talc pleurodesis, occurring in 24 (31%) of 78 patients who completed VAT-PP versus ten (14%) of 73 patients who completed talc pleurodesis (p=0·019), as were respiratory complications (19 [24%] vs 11 [15%]; p=0·22) and air-leak beyond 10 days (five [6%] vs one [1%]; p=0·21), although not significantly so. Median hospital stay was longer at 7 days (IQR 5-11) in patients who received VAT-PP compared with 3 days (2-5) for those who received talc pleurodesis (p<0·0001). INTERPRETATION: VAT-PP is not recommended to improve overall survival in patients with pleural effusion due to malignant pleural mesothelioma, and talc pleurodesis might be preferable considering the fewer complications and shorter hospital stay associated with this treatment. FUNDING: BUPA Foundation.
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Neoplasias Pulmonares/terapia , Mesotelioma/terapia , Neoplasias Pleurais/terapia , Pleurodese/métodos , Talco/administração & dosagem , Cirurgia Torácica Vídeoassistida/métodos , Idoso , Custos e Análise de Custo , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/economia , Masculino , Mesotelioma/economia , Mesotelioma Maligno , Neoplasias Pleurais/economia , Neoplasias Pleurais/mortalidade , Pleurodese/economia , Pleurodese/mortalidade , Anos de Vida Ajustados por Qualidade de Vida , Talco/economia , Cirurgia Torácica Vídeoassistida/economia , Cirurgia Torácica Vídeoassistida/mortalidade , Resultado do TratamentoRESUMO
Primary spontaneous pneumothorax (PSP) affects young healthy people with a significant recurrence rate. Recent advances in treatment have been variably implemented in clinical practice. This statement reviews the latest developments and concepts to improve clinical management and stimulate further research.The European Respiratory Society's Scientific Committee established a multidisciplinary team of pulmonologists and surgeons to produce a comprehensive review of available scientific evidence.Smoking remains the main risk factor of PSP. Routine smoking cessation is advised. More prospective data are required to better define the PSP population and incidence of recurrence. In first episodes of PSP, treatment approach is driven by symptoms rather than PSP size. The role of bullae rupture as the cause of air leakage remains unclear, implying that any treatment of PSP recurrence includes pleurodesis. Talc poudrage pleurodesis by thoracoscopy is safe, provided calibrated talc is available. Video-assisted thoracic surgery is preferred to thoracotomy as a surgical approach.In first episodes of PSP, aspiration is required only in symptomatic patients. After a persistent or recurrent PSP, definitive treatment including pleurodesis is undertaken. Future randomised controlled trials comparing different strategies are required.
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Pneumotórax/diagnóstico , Pneumotórax/epidemiologia , Pneumotórax/cirurgia , Comitês Consultivos , Antiperspirantes , Humanos , Pleurodese , Guias de Prática Clínica como Assunto , Recidiva , Fumar/efeitos adversos , Sociedades Médicas , Talco/uso terapêutico , Cirurgia Torácica Vídeoassistida , ToracotomiaRESUMO
We hypothesized that small molecule transcriptional perturbation could be harnessed to target a cellular dependency involving protein arginine methyltransferase 5 (PRMT5) in the context of methylthioadenosine phosphorylase (MTAP) deletion, seen frequently in malignant pleural mesothelioma (MPM). Here we show, that MTAP deletion is negatively prognostic in MPM. In vitro, the off-patent antibiotic Quinacrine efficiently suppressed PRMT5 transcription, causing chromatin remodelling with reduced global histone H4 symmetrical demethylation. Quinacrine phenocopied PRMT5 RNA interference and small molecule PRMT5 inhibition, reducing clonogenicity in an MTAP-dependent manner. This activity required a functional PRMT5 methyltransferase as MTAP negative cells were rescued by exogenous wild type PRMT5, but not a PRMT5E444Q methyltransferase-dead mutant. We identified c-jun as an essential PRMT5 transcription factor and a probable target for Quinacrine. Our results therefore suggest that small molecule-based transcriptional perturbation of PRMT5 can leverage a mutation-selective vulnerability, that is therapeutically tractable, and has relevance to 9p21 deleted cancers including MPM.
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Transformação Celular Neoplásica/genética , Regulação Neoplásica da Expressão Gênica , Proteína-Arginina N-Metiltransferases/genética , Purina-Núcleosídeo Fosforilase/genética , Biomarcadores Tumorais , Transformação Celular Neoplásica/metabolismo , Deleção de Genes , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Inativação Gênica , Humanos , Estimativa de Kaplan-Meier , Mesotelioma Maligno/genética , Mesotelioma Maligno/mortalidade , Mesotelioma Maligno/patologia , Prognóstico , Proteína-Arginina N-Metiltransferases/metabolismo , Proteínas Proto-Oncogênicas c-jun/metabolismo , Purina-Núcleosídeo Fosforilase/metabolismo , Quinacrina/farmacologia , Transcrição GênicaRESUMO
BACKGROUND: The role of TNFalpha in cancer is complex with both pro-tumourigenic and anti-tumourigenic roles proposed. We hypothesised that anatomical microlocalisation is critical for its function. METHODS: This study used immunohistochemistry to investigate the expression of TNFalpha in the tumour islets and stroma with respect to survival in 133 patients with surgically resected NSCLC. RESULTS: TNFalpha expression was increased in the tumour islets of patients with above median survival (AMS) compared to those with below median survival (BMS)(p = 0.006), but similar in the stroma of both groups. Increasing tumour islet TNFalpha density was a favorable independent prognostic indicator (p = 0.048) while stromal TNFalpha density was an independent predictor of reduced survival (p = 0.007). Patients with high TNFalpha expression (upper tertile) had a significantly higher 5-year survival compared to patients in the lower tertile (43% versus 22%, p = 0.01). In patients with AMS, 100% of TNFalpha+ cells were macrophages and mast cells, compared to only 28% in the islets and 50% in the stroma of BMS patients (p < 0.001). CONCLUSIONS: The expression of TNFalpha in the tumour islets of patients with NSCLC is associated with improved survival suggesting a role in the host anti-tumour immunological response. The expression of TNFalpha by macrophages and mast cells is critical for this relationship.
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Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Fator de Necrose Tumoral alfa/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Grandes/metabolismo , Carcinoma de Células Grandes/mortalidade , Carcinoma de Células Grandes/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Técnicas Imunoenzimáticas , Neoplasias Pulmonares/patologia , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Mastócitos/metabolismo , Mastócitos/patologia , Pessoa de Meia-Idade , Prognóstico , Células Estromais/metabolismo , Células Estromais/patologia , Taxa de SobrevidaRESUMO
BACKGROUND: We have previously demonstrated that tumour islet infiltration by macrophages is associated with extended survival (ES) in NSCLC. We therefore hypothesised that patients with improved survival would have high tumour islet expression of chemokine receptors known to be associated with favourable prognosis in cancer. This study investigated chemokine receptor expression in the tumour islets and stroma in NSCLC. METHODS: We used immunohistochemistry to identify cells expressing CXCR1, CXCR2, CXCR3, CXCR4, CXCR5 and CCR1 in the tumour islets and stroma in 20 patients with surgically resected NSCLC. Correlations were made with macrophage and mast cell expression. RESULTS: There was increased expression of CXCR2, CXCR3, and CCR1 in the tumour islets of ES compared with poor survival (PS) patients (p = 0.007, 0.01, and 0.002, respectively). There was an association between 5 year survival and tumour islet CXCR2, CXCR3 and CCR1 density (p = 0.02, 0.003 and <0.001, respectively) as well as stromal CXCR3 density (p = 0.003). There was a positive correlation between macrophage density and CXCR3 expression (rs = 0.520, p = 0.02) and between mast cell density and CXCR3 expression (rs = 0.499, p = 0.03) in the tumour islets. CONCLUSION: Above median expression of CXCR2, CXCR3 and CCR1 in the tumour islets is associated with increased survival in NSCLC, and expression of CXCR3 correlates with increased macrophage and mast cell infiltration in the tumour islets.
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Carcinoma Pulmonar de Células não Pequenas/imunologia , Células Epiteliais/imunologia , Neoplasias Pulmonares/imunologia , Receptores de Quimiocinas/análise , Células Estromais/imunologia , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Quimiotaxia , Distribuição de Qui-Quadrado , Células Epiteliais/patologia , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Macrófagos/imunologia , Masculino , Mastócitos/imunologia , Pessoa de Meia-Idade , Receptores CCR1/análise , Receptores CXCR3/análise , Receptores de Interleucina-8B/análise , Células Estromais/patologia , Fatores de Tempo , Resultado do Tratamento , Regulação para CimaRESUMO
Introduction: One of the most debilitating symptoms of malignant pleural mesothelioma (MPM) is dyspnoea caused by pleural effusion. MPM can be complicated by the presence of tumour on the visceral pleura preventing the lung from re-expanding, known as trapped lung (TL). There is currently no consensus on the best way to manage TL. One approach is insertion of an indwelling pleural catheter (IPC) under local anaesthesia. Another is video-assisted thoracoscopic partial pleurectomy/decortication (VAT-PD). Performed under general anaesthesia, VAT-PD permits surgical removal of the rind of tumour from the visceral pleura thereby allowing the lung to fully re-expand. Methods and analysis: MesoTRAP is a feasibility study that includes a pilot multicentre, randomised controlled clinical trial comparing VAT-PD with IPC in patients with TL and pleural effusion due to MPM. The primary objective is to measure the SD of visual analogue scale scores for dyspnoea following randomisation and examine the patterns of change over time in each treatment group. Secondary objectives include documenting survival and adverse events, estimating the incidence and prevalence of TL in patients with MPM, examining completion of alternative forms of data capture for economic evaluation and determining the ability to randomise 38 patients in 18 months. Ethics and dissemination: This study was approved by the East of England-Cambridge Central Research Ethics Committee and the Health Research Authority (reference number 16/EE/0370). We aim to publish the outputs of this work in international peer-reviewed journals compliant with an Open Access policy. Trial registration: NCT03412357.
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Neoplasias Pulmonares/cirurgia , Mesotelioma/cirurgia , Derrame Pleural Maligno/cirurgia , Neoplasias Pleurais/cirurgia , Pleurodese/métodos , Cirurgia Torácica Vídeoassistida/métodos , Adulto , Cateteres de Demora , Ensaios Clínicos Fase III como Assunto , Inglaterra/epidemiologia , Estudos de Viabilidade , Feminino , Humanos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/mortalidade , Masculino , Mesotelioma/complicações , Mesotelioma/mortalidade , Mesotelioma Maligno , Estudos Multicêntricos como Assunto , Estudos Observacionais como Assunto , Projetos Piloto , Derrame Pleural Maligno/etiologia , Derrame Pleural Maligno/mortalidade , Neoplasias Pleurais/complicações , Neoplasias Pleurais/mortalidade , Pleurodese/efeitos adversos , Pleurodese/instrumentação , Ensaios Clínicos Controlados Aleatórios como Assunto , Tamanho da Amostra , Análise de Sobrevida , Cirurgia Torácica Vídeoassistida/efeitos adversos , Cirurgia Torácica Vídeoassistida/instrumentação , Resultado do TratamentoRESUMO
BACKGROUND: To study the feasibility and efficacy of video-assisted thoracoscopic (VAT) placement of the left ventricular pacing lead for cardiac resynchronization therapy (CRT) where the conventional transvenous coronary sinus approach has failed. METHODS: Seventeen patients underwent the VAT procedure. Indications for CRT were ischemic cardiomyopathy in six patients and nonischemic cardiomyopathy in 11. The procedure was performed under general anesthesia with single-lung ventilation. Three 2-cm incisions were used on the left chest wall to place the screw-in lead near the obtuse marginal arteries high on the lateral wall of the left ventricle (LV). RESULTS: The VATS approach was successful in 13/17 (76%) patients. Median procedure time was 75 minutes (range 55-135). A learning curve was observed that appeared to plateau at 75 minutes procedure time after four cases. Median length of hospital stay was 2 days (range 2-8) with one patient requiring intensive care. Satisfactory thresholds and impedances of 2.3 +/- 0.9 V/0.5 ms and 560 ohms, respectively, were achieved at mean follow-up of 226 days. All patients reported symptomatic benefit with reduction in New York Heart Association score from III preoperatively to II postoperatively. CONCLUSIONS: VAT placement of the epicardial pacing lead is feasible, safe, and efficacious. It should be considered in cases where the transvenous route has failed or as an alternative in prolonged or hazardous transvenous procedures.
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Arritmias Cardíacas/patologia , Arritmias Cardíacas/prevenção & controle , Estimulação Cardíaca Artificial/métodos , Eletrodos Implantados , Marca-Passo Artificial , Implantação de Prótese/métodos , Cirurgia Torácica Vídeoassistida/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cirurgia Assistida por Computador/métodos , Resultado do Tratamento , Disfunção Ventricular Esquerda/patologia , Disfunção Ventricular Esquerda/prevenção & controleRESUMO
OBJECTIVE: Extrapleural pneumonectomy (EPP) has high mortality and morbidity; radical pleurectomy decortication (P/D) carries less mortality but still significant morbidity. This surgery is not suitable for many patients with malignant pleural mesothelioma (MPM) for whom video assisted thoracic surgery (VATS) offers a minimally invasive alternative. We aimed to assess the role of VATS decortication for MPM. METHODS: Over a 9-year period 208 patients underwent therapeutic surgery for MPM in our unit. One hundred and twelve of the patients underwent EPP, 29 had a P/D and 67 had VATS decortication. Sixty-three of the 208 patients (EPP n=13, P/D n=8 and VATS decortication n=42) were 65 years of age or older at the time of the operation (57 males and 6 females, age 70 (65-80) years). In this group we analyzed perioperative morbidity and mortality and long-term survival data using the Kaplan-Meier method. RESULTS: Postoperative stay and 30-day mortality was significantly lower for VATS P/D than for EPP (14.3 days vs 36.6 days, p<0.05 and mortality 7.1% vs 23%, respectively). There was no significant difference in the overall mean survival between the two groups (11.5 months for EPP and 14 months for VATS P/D, p=0.6). CONCLUSION: VATS decortication should be considered in the therapeutic strategy for MPM.
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Mesotelioma/cirurgia , Neoplasias Pleurais/cirurgia , Pneumonectomia/métodos , Cirurgia Torácica Vídeoassistida/normas , Idoso , Idoso de 80 Anos ou mais , Causas de Morte , Estudos de Viabilidade , Feminino , Humanos , Masculino , Mesotelioma/mortalidade , Neoplasias Pleurais/mortalidade , Cirurgia Torácica Vídeoassistida/métodos , Resultado do TratamentoRESUMO
OBJECTIVE: Localised malignant pleural mesotheliomas are very rare and although there are sporadic reports in the literature showing that they have a different biological behaviour compared to diffuse MPM there is no major series published demonstrating results of surgical treatment. We present our experience in treating these tumours. METHODS: Over an 8-year period we performed radical or debulking surgery in 218 patients with MPM. Ten of these patients had localised chest wall tumours and a biopsy either highly suspicious or confirming malignant pleural mesothelioma. They were all male with an average age of 65.9 (56-80) years. Three of the tumours were epithelioid, three biphasic and three sarcomatoid. They all had chest wall resections, with limited lung resections where the tumours were infiltrating the lung and reconstruction using a double prolene mesh and orthopaedic cement. Perioperative events and long-term survival were analysed and survival was compared to survival following operations for diffuse malignant pleural mesothelioma. RESULTS: There was no 30-day mortality with only two patients suffering from pleural collections that required ultrasound guided drainage 2 and 8 weeks after the operation. Two patients died from disease progression 3 and 10 months after the operation. Using Kaplan-Meier analysis the mean survival was 56 months. CONCLUSION: Our results suggest that surgery is indicated in treating localised MPM even in T4 (diffuse chest wall involvement) tumours but pleuropneumonectomy is not necessary. These tumours seem to have a different biological behaviour compared to diffuse MPM but further research, including identification of possibly different biological markers is necessary.
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Mesotelioma/cirurgia , Neoplasias Pleurais/cirurgia , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Humanos , Masculino , Mesotelioma/mortalidade , Mesotelioma/patologia , Pessoa de Meia-Idade , Derrame Pleural/etiologia , Derrame Pleural/terapia , Neoplasias Pleurais/mortalidade , Neoplasias Pleurais/patologia , Análise de SobrevidaRESUMO
OBJECTIVES: In the preoperative workup for radical surgery for malignant pleural mesothelioma (MPM), mediastinal lymph node staging, diagnostic pleural biopsies and effusion control with talc pleurodesis are required. We present a new technique combining these objectives via a single cervical incision using the videomediastinoscope and demonstrate its clinical benefits. METHODS: Video-assisted cervical thoracoscopy (VACT) was attempted in 15 patients (13 male, mean age 57 years), who were potential candidates for radical surgery. Following conventional cervical videomediastinoscopy, a 5 mm thoracoscope was advanced into the relevant pleural cavity through the mediastinoscope via a mediastinal pleurotomy. Pleural biopsies were taken followed by talc insufflation and cervical tube drainage. The clinical outcome was compared with 26 patients undergoing a staged preoperative workup during the same period. RESULTS: VACT was successful in 10 patients (66.6%). In five patients (three right and two left), thoracoscopy was abandoned due to excessive mediastinal fat (1), thick pleura (2) and inability to enter the left hemithorax (2). Mean operative time was 71 (65-90) min and hospital stay 4 (3-7) days. One patient suffered recurrent laryngeal nerve palsy and one had persistent air leak. Ten patients subsequently underwent radical surgery. Time to radical surgery was significantly reduced by nearly 2 months in VACT patients (28+/-17 days vs 87+/-56 days, p<0.001). CONCLUSIONS: The benefits of this approach include reduction in postoperative pain, risk of biopsy site tumour seeding, and preoperative delay to radical surgery. VACT is feasible in right-sided mesothelioma but has not yet been validated on the left.
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Mesotelioma/diagnóstico , Neoplasias Pleurais/diagnóstico , Pleurodese/métodos , Cirurgia Torácica Vídeoassistida/métodos , Adulto , Idoso , Biópsia , Drenagem/métodos , Estudos de Viabilidade , Feminino , Humanos , Masculino , Mesotelioma/patologia , Mesotelioma/terapia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Derrame Pleural Maligno/terapia , Neoplasias Pleurais/patologia , Neoplasias Pleurais/terapia , Talco/uso terapêuticoRESUMO
The 8th tumour, node and metastasis (TNM) revision of the staging classification for lung cancer has attempted to clarify the different properties of four distinct clinical presentations: synchronous multiple primary lung cancers; primary tumour with intrapulmonary metastases; pneumonic-type adenocarcinoma and multiple ground glass/lepidic lesions. The respective biological profiles determine different surgical strategies for each category. Accurate preoperative histological confirmation is required to identify synchronous primary tumours which should then be managed as two separate episodes within the confines of patient characteristics. Equally important is the confirmation of intrapulmonary metastasis which indicates a more conservative resection of the smaller lesion. In contrast, pneumonic-type adenocarcinoma may require larger parenchymal resection to achieve anatomical clearance but also symptom relief. Multiple subsolid lesions require a carefully planned strategy of parenchymal sparing and possible observation of less malignant abnormalities. In all the above situations careful clinical, radiological and pathological assessment is imperative to avoid one embarking on inappropriate invasive management. Either when the widespread nature of the disease renders extensive surgery futile or the relative benign or pre-malignant nature of the multiple lesions imply that the risks of surgery outweigh the prognostic benefits.
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Extended pleurectomy/decortication (EPD) has been formally defined but there remain technical areas of debate between practitioners. This is partly attributable to the relative rarity of this operation which is largely confined to a small number of specialist centres. Nevertheless, there is a widespread acceptance that extended pleurectomy/decortication (P/D) is a realistic and favourable alternative to extrapleural pneumonectomy. There may, however, remain a small number of clinical cases where this more extensive operation may be indicated. Preservation of the lung has widened the selection criteria for this form of radical mesothelioma surgery but there remain important factors to consider when offering extended P/D. In many patients with poorer prognostic factors the less radical operation of video assisted partial pleurectomy may be preferable. However, a randomized trial showed no survival benefit for this operation over simple talc pleurodesis. The future for P/D may also lie in the outcome of the MARS2 randomized controlled trial which will report in the next few years. Meanwhile there is a clinical and ethical dilemma when asked to perform this operation outside of the context of a clinical trial in the face of the lack of high grade evidence. The role of P/D is in one respect expanding but this may be short lived pending the findings of its assessment against non-surgical treatment.
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Malignant mesothelioma (MM) is poorly responsive to systemic cytotoxic chemotherapy and invariably fatal. Here we describe a screen of 94 drugs in 15 exome-sequenced MM lines and the discovery of a subset defined by loss of function of the nuclear deubiquitinase BRCA associated protein-1 (BAP1) that demonstrate heightened sensitivity to TRAIL (tumour necrosis factor-related apoptosis-inducing ligand). This association is observed across human early passage MM cultures, mouse xenografts and human tumour explants. We demonstrate that BAP1 deubiquitinase activity and its association with ASXL1 to form the Polycomb repressive deubiquitinase complex (PR-DUB) impacts TRAIL sensitivity implicating transcriptional modulation as an underlying mechanism. Death receptor agonists are well-tolerated anti-cancer agents demonstrating limited therapeutic benefit in trials without a targeting biomarker. We identify BAP1 loss-of-function mutations, which are frequent in MM, as a potential genomic stratification tool for TRAIL sensitivity with immediate and actionable therapeutic implications.
Assuntos
Neoplasias Pulmonares/fisiopatologia , Mesotelioma/fisiopatologia , Proteínas Repressoras/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Ubiquitina Tiolesterase/metabolismo , Animais , Linhagem Celular Tumoral , Humanos , Mesotelioma Maligno , CamundongosRESUMO
OBJECTIVE: To compare the outcomes of extrapleural pneumonectomy (EPP) and radical pleurectomy/decortication (P/D) for N2 malignant pleural mesothelioma (MM). PATIENTS AND METHODS: In a retrospective case-control study we analysed the results of the 57 patients [49 male and 8 female, median age 59 (range 14-70) years] who underwent radical surgery for MM found to have pathological N2 disease over a 7-year-period. EPP was performed on 45 and P/D on 12 patients. Prognostic factors, postoperative course, pathological data and postoperative survival were analysed. RESULTS: Those in the P/D group were significantly older (median age 62 vs 58 years, p=0.03) than in the EPP group. There was no difference in postoperative hospital stay (p=0.1) nor T stage (p=0.7) between the groups. There were no significant differences in the proportion of patients undergoing some adjuvant therapy in each group (p=0.2). Mean survival from diagnosis was 15 months in the EPP group and 16 months for those who underwent P/D (p=0.4). CONCLUSIONS: Preservation of the lung during radical surgery for N2 MM does not compromise survival even in an older group population. We therefore now have ceased to perform EPP in cases of N2 disease and we make every effort to accurately stage patients with mediastinoscopy to identify them.
Assuntos
Mesotelioma/cirurgia , Pleura/cirurgia , Neoplasias Pleurais/cirurgia , Pneumonectomia/métodos , Adolescente , Adulto , Fatores Etários , Idoso , Estudos de Casos e Controles , Terapia Combinada/métodos , Feminino , Humanos , Estimativa de Kaplan-Meier , Tempo de Internação , Masculino , Mesotelioma/mortalidade , Mesotelioma/patologia , Mesotelioma/terapia , Pessoa de Meia-Idade , Neoplasias Pleurais/mortalidade , Neoplasias Pleurais/patologia , Neoplasias Pleurais/terapia , Período Pós-Operatório , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: To examine the short- and long-term results of right extrapleural pneumonectomy (EPP) for malignant pleural mesothelioma (MM) via median sternotomy or thoracotomy. METHODS: We analysed the results of EPP in consecutive patients with early stage MM undergoing a radical surgery protocol for MM over a 7-year period. Initially thoracotomy, but later median sternotomy, was the incision of choice for right-sided tumours. The effects of the change of approach on perioperative course and survival were analysed. RESULTS: EPP was performed in 105 patients (50 left thoracotomy, 22 right thoracotomy, 28 sternotomy, 5 combined sternotomy and right thoracotomy). Operation time was faster with median sternotomy than right thoracotomy (p=0.008). Right thoracotomy was associated with higher epidural infusion volume in the first 3 days than median sternotomy (p<0.001). There were fewer postoperative complications in the sternotomy group (p=0.05). There were no differences in pathological stage, completeness of resection or duration of postoperative stay. Median survival following left thoracotomy, right thoracotomy and median sternotomy was 18.3, 8.5 and 17.7 months, respectively (p=0.02). Planned neoadjuvant or adjuvant chemotherapy was more common following median sternotomy than right thoracotomy (p=0.01). However, compared with the left thoracotomy and sternotomy groups, right EPP performed via thoracotomy was an independent predictor of poor prognosis (hazard ratio 2.3 (95% confidence intervals, CI 1.3-4.1), p=0.02). No wound complications or tumour recurrence have been observed following median sternotomy. CONCLUSIONS: Median sternotomy should be considered as an alternative approach to thoracotomy for right EPP.