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BACKGROUND: Mapping of the pulmonary lymphatic system by near-infrared (NIR) fluorescence imaging might not always identify the first lymph node relay. The aim of this study was to determine the clinicopathologic factors allowing the identification of sentinel lymph nodes (SLNs) by NIR fluorescence imaging in thoracic surgery for non-small-cell lung cancer (NSCLC). METHODS: We conducted a retrospective review of 92 patients treated for suspected or confirmed cN0 lung cancer with curative intent who underwent an intraoperative injection of indocyanine green (ICG) either by direct peritumoral injection or by endobronchial injection using electromagnetic navigational bronchoscopy (ENB). After exclusion of patients for technical failure, benign disease and metastasis, we analyzed the clinicopathologic findings of 65 patients treated for localized-stage NSCLC, comparing the group with identification of SLNs (SLN-positive group) with the group without identification of SLNs (SLN-negative group). RESULTS: Forty-eight patients (73.8%) were SLN-positive. Patients with SLN positivity were more frequently female (50%) than the SLN-negative patients were (11.8%) (p = 0.006). The mean value of diffusing capacity for carbon monoxide (DLCO) was lower among the patients in the SLN-negative group (64.7% ± 16.7%) than the SLN-positive group (77.6% ± 17.2%, p < 0.01). The ratio of forced expiratory volume in one second to forced vital capacity (FEV1/FCV) was higher in the SLN-positive group (69.0% vs. 60.8%, p = 0.02). Patients who were SLN-negative were characterized by a severe degree of emphysema (p = 0.003). There was no significant difference in pathologic characteristics. On univariate analyses, age, female sex, DLCO, FEV1/FVC, degree of emphysema, and tumor size were significantly associated with SLN detection. On multivariate analysis, DLCO > 75% (HR = 4.92, 95% CI: 1.27-24.7; p = 0.03) and female sex (HR = 5.55, 95% CI: 1.25-39.33; p = 0.04) were independently associated with SLN detection. CONCLUSIONS: At a time of resurgence in the use of the sentinel lymph node mapping technique in the field of thoracic surgery, this study enabled us to identify, using multivariate analysis, two predictive factors for success: DLCO > 75% and female sex. Larger datasets are needed to confirm our results.
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Carcinoma Pulmonar de Células não Pequenas , Enfisema , Neoplasias Pulmonares , Linfonodo Sentinela , Humanos , Feminino , Linfonodo Sentinela/diagnóstico por imagem , Linfonodo Sentinela/patologia , Linfonodo Sentinela/cirurgia , Carcinoma Pulmonar de Células não Pequenas/patologia , Biópsia de Linfonodo Sentinela/métodos , Metástase Linfática/patologia , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/patologia , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Linfonodos/patologia , Enfisema/patologia , Enfisema/cirurgiaRESUMO
BACKGROUND: Several regulatory agencies have approved the use of the neoadjuvant chemo-immunotherapy for resectable stage II and III of non-small cell lung cancer (NSCLC) and numerous trials investigating novel agents are underway. However, significant concerns exist around the feasibility and safety of offering curative surgery to patients treated within such pathways. The goal in this study was to evaluate the impact of a transition towards a large-scale neoadjuvant therapy program for NSCLC. METHODS: Medical charts of patients with clinical stage II and III NSCLC who underwent resection from January 2015 to December 2020 were reviewed. The primary outcome was perioperative complication rate between neoadjuvant-treated versus upfront surgery patients. Multivariable logistic regression estimated occurrence of postoperative complications and overall survival was assessed as an exploratory secondary outcome by Kaplan-Meier and Cox-regression analyses. RESULTS: Of the 428 patients included, 106 (24.8%) received neoadjuvant therapy and 322 (75.2%) upfront surgery. Frequency of minor and major postoperative complications was similar between groups (P = .22). Occurrence in postoperative complication was similar in both cohort (aOR = 1.31, 95% CI 0.73-2.34). Neoadjuvant therapy administration increased from 10% to 45% with a rise in targeted and immuno-therapies over time, accompanied by a reduced rate of preoperative radiation therapy use. 1-, 2-, and 5-year overall survival was higher in neoadjuvant therapy compared to upfront surgery patients (Log-Rank P = .017). CONCLUSIONS: No significant differences in perioperative outcomes and survival were observed in resectable NSCLC patients treated by neoadjuvant therapy versus upfront surgery. Transition to neoadjuvant therapy among resectable NSCLC patients is safe and feasible from a surgical perspective.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Terapia Neoadjuvante , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Terapia Neoadjuvante/métodos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Pneumonectomia , Estudos Retrospectivos , Taxa de Sobrevida , Complicações Pós-Operatórias/epidemiologia , Resultado do Tratamento , Estadiamento de Neoplasias , SeguimentosRESUMO
PURPOSE OF REVIEW: With increased detection of early-stage non-small cell lung cancer (NSCLC) owing to screening, determining optimal management increasingly hinges on assessing resectability and operability. Resectability refers to the feasibility of achieving microscopically negative margins based on tumour size, location and degree of local invasion and achieving an anatomical lobar resection. Operability reflects the patient's tolerance for resection based on comorbidities, cardiopulmonary reserve and frailty. Standardized criteria help guide these assessments, but application variability contributes to practice inconsistencies. This review synthesizes a strategic approach to evaluating resectability and operability in contemporary practice. Standardization promises reduced care variability and optimized patient selection to maximize curative outcomes in this new era of early detection. RECENT FINDINGS: Recent pivotal trials demonstrate equivalency of sublobar resection to lobectomy for small, peripheral, node-negative NSCLC, expanding options for parenchymal preservation in borderline surgical candidates. Furthermore, recent phase 3 trials have highlighted the benefit of chemoimmunotherapy as a neoadjuvant treatment with an excellent pathological response and a down staging of the tumour, improving the resectability of the early-stage NSCLC. A good assessment of the operability and resectability is paramount in order to offer the best course of treatment for our patients. European and American societies have issued recommendations to help clinicians assess the cardiopulmonary function and predict the extension of pulmonary resection that could afford the patient. This operability assessment is closely linked with the evaluated tumour resectability which will determine the extension of pulmonary resection that is needed for the patient in order to achieve a good oncological outcome. Some major progresses have been done recently to improve the operability and resectability of patients. For instance, prehabilitation program allows better postoperative morbidity. Some studies have shown a potential good oncological outcome with sublobar resection expending access to surgery for patient with reduced lung function. Some others have identified the neoadjuvant immunochemotherapy as a potential solution for downstaging tumours. Work-up of early-stage NSCLC is a key moment and has to be done thoroughly and in full knowledge of the recent findings in order to propose the most appropriate treatment for the patient.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias , Pneumonectomia , Carcinoma de Pequenas Células do Pulmão/patologiaRESUMO
OBJECTIVES: Although segmentectomy is steadily increasing in early-stage non-small-cell lung cancer, recurrence in the ipsilateral lobe is also increasing. Completion lobectomy (CL) is a challenging procedure that has already been described in a few studies using video-assisted thoracic surgery or thoracotomy. In this study, we aimed to show the feasibility and safety of robot-assisted thoracic surgery in cases of CL. METHODS: Among 2073 major resections performed between January 2018 and september 2022 in the Department of Thoracic Surgery at Nancy University Regional Hospital, we retrospectively included patients who underwent CL by robot-assisted thoracic surgery after previous segmentectomy for non-small-cell lung cancer. Data and perioperative results were described and analysed. RESULTS: Seventeen patients underwent CL with a median recurrence time after previous segmentectomy of 18 months [interquartile range (IQR): 12]. Four patients (23.5%) had a pulmonary artery injury that was controlled, and no conversion to open thoracotomy was needed. The operative time was 150 min (IQR: 20), and blood loss was 300 ml (IQR: 150). The median postoperative chest tube duration was 2 days (IQR: 1), and the length of hospital stay was 3 days (IQR: 3), with no postoperative deaths. CONCLUSIONS: Completion lobectomy is a challenging procedure due to severe adhesions surrounding vessels, which potentially could cause higher rate of PA bleeding than conventional surgeries. With experienced team and surgeons, CL with robotic surgery may be reported as a safe and feasible procedure.
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Radiation therapy and platinum-based chemotherapy are common treatments for lung cancer patients. Several factors are considered for the low overall survival rate of lung cancer, such as the patient's physical state and the complex heterogeneity of the tumor, which leads to resistance to the treatment. Consequently, precision medicines are needed for the patients to improve their survival and their quality of life. Until now, no patient-derived tumoroid model has been reported to predict the efficiency of radiation therapy in non-small-cell lung cancer. Using our patient-derived tumoroid model, we report that this model could be used to evaluate the efficiency of radiation therapy and cisplatin-based chemotherapy in non-small-cell lung cancer. In addition, these results can be correlated to clinical outcomes of patients, indicating that this patient-derived tumoroid model can predict the response to radiotherapy and chemotherapy in non-small-cell lung cancer.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Assistência Perioperatória , Terapia Neoadjuvante , Quimioterapia Adjuvante , Protocolos de Quimioterapia Combinada AntineoplásicaRESUMO
Synthetic 3D multicellular systems derived from patient tumors, or tumoroids, have been developed to complete the cancer research arsenal and overcome the limits of current preclinical models. They aim to represent the molecular and structural heterogeneity of the tumor micro-environment, and its complex network of interactions, with greater accuracy. They are more predictive of clinical outcomes, of adverse events, and of resistance mechanisms. Thus, they increase the success rate of drug development, and help clinicians in their decision-making process. Lung cancer remains amongst the deadliest of diseases, and still requires intensive research. In this review, we analyze the merits and drawbacks of the current preclinical models used in lung cancer research, and the position of tumoroids. The introduction of immune cells and healthy regulatory cells in autologous tumoroid models has enabled their application to most recent therapeutic concepts. The possibility of deriving tumoroids from primary tumors within reasonable time has opened a direct approach to patient-specific features, supporting their future role in precision medicine.
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Patient-derived tumoroid (PDT) has been developed and used for anti-drug screening in the last decade. As compared to other existing drug screening models, a PDT-based in vitro 3D cell culture model could preserve the histological and mutational characteristics of their corresponding tumors and mimic the tumor microenvironment. However, few studies have been carried out to improve the microvascular network connecting the PDT and its surrounding microenvironment, knowing that poor tumor-selective drug transport and delivery is one of the major reasons for both the failure of anti-cancer drug screens and resistance in clinical treatment. In this study, we formed vascularized PDTs in six days using multiple cell types which maintain the histopathological features of the original cancer tissue. Furthermore, our results demonstrated a vascular network connecting PDT and its surrounding microenvironment. This fast and promising PDT model opens new perspectives for personalized medicine: this model could easily be used to test all therapeutic treatments and could be connected with a microfluidic device for more accurate drug screening.
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Background: Stereotactic radiotherapy for localised stage non-small-cell lung carcinoma (NSCLC) is an alternative indication for patients who are inoperable or refuse surgery. A study showed that the microscopic tumour extension (ME) of NSCLC varied according to the histological type, which allowed us to deduce adapted margins for the clinical target volume (CTV). However, to date, no study has been able to define the most relevant margins for patients with stage 1 tumours. Methods: We performed a retrospective analysis including patients with adenocarcinoma (ADC) or squamous cell carcinoma (SCC) of localised stage T1N0 or T2aN0 who underwent surgery. The ME was measured from this boundary. The profile of the type of tumour spread was also evaluated. Results: The margin required to cover the ME of a localised NSCLC with a 95% probability is 4.4 mm and 2.9 mm for SCC and ADC, respectively. A significant difference in the maximum distance of the ME between the tumour-infiltrating lymphocytes (TILs), 0−10% and 50−90% (p < 0.05), was noted for SCC. There was a significant difference in the maximum ME distance based on whether the patient had chronic obstructive pulmonary disease (COPD) (p = 0.011) for ADC. Multivariate analysis showed a statistically significant relationship between the maximum microextension distance and size with the shrinkage coefficient. Conclusion: This study definitively demonstrated that the ME depends on the pathology subtype of NSCLC. According to International Commission on Radiation Units and Measurements (ICRU) reports, 50, 62 and 83 CTV margins, proposed by these results, should be added to the GTV (Gross tumour volume). When stereotactic body radiation therapy is used, this approach should be considered in conjunction with the dataset and other margins to be applied.
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Occult micrometastases can be missed by routine pathological analysis. Mapping of the pulmonary lymphatic system by near-infrared (NIR) fluorescence imaging can identify the first lymph node relay. This sentinel lymph node (SLN) can be analyzed by immunohistochemistry (IHC), which may increase micrometastasis detection and improve staging. This study analyzed the feasibility and safety of identifying SLNs in thoracic surgery by NIR fluorescence imaging in non-small cell lung cancer (NSCLC). This was a prospective, observational, single-center study. Eighty adult patients with suspected localized stage NSCLC (IA1 to IIA) were included between December 2020 and May 2022. All patients received an intraoperative injection of indocyanine green (ICG) directly in the peri tumoural area or by electromagnetic navigational bronchoscopy (ENB). The SLN was then assessed using an infrared fluorescence camera. SLN was identified in 60 patients (75%). Among them, 36 SLNs associated with a primary lung tumor were analyzed by IHC. Four of them were invaded by micrometastases (11.1%). In the case of pN0 SLN, the rest of the lymphadenectomy was cancer free. The identification of SLNs in thoracic surgery by NIR fluorescence imaging seems to be a feasible technique for improving pathological staging.
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Introduction: The place of segmentectomy in the management of lung cancer is shifting following the inspiring results of the Japanese JCOG0802 trial. I n this study, authors suggested that performing segmentectomy would require in an optimal way an intraoperative confirmation of pN0 tumor with a frozen section. Our objective was to determine whether the proposed technique, i.e. adjacent lymph node analysis, is consistent with the results of our study on sentinel lymph node (SLN) detection using fluorescence. Methods: This is a retrospective, observational, single center study. Eighty-one patients with suspected localized stage NSCLC (IA to IIA) were included between December 2020 and March 2022. All patients received an intra-operative injection of indocyanine green (ICG) directly in the peritumoral area or by electromagnetic navigational bronchoscopy (ENB). The SLN was then assessed by using an infrared fluorescence camera. Results: In our cohort, SLN was identified in 60/81 patients (74.1%). In 15/60 patients with identified SLN (25%), NIR-guided SLN was concordant with the suggestions of JCOG0802 study. A retrospective SLN pathological analysis was performed in 43 patients/60 cases with identified SLN (71.2%), including 37 cases of malignant disease. Occult micro-metastases were found in 4 patients out of 37 SLN analyzed, leading to a 10.8% upstaging with NIR-guided SLN analysis. Dicussion: At the time of segmentectomies, ICG technique allowed the identification of the SLN in a high percent of cases and in some areas usually out of the recommended stations for lymph node dissection.
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BACKGROUND: We sought to evaluate prognostic value of neutrophil-to-lymphocyte ratio (NLR) in surgically resected non-small cell lung cancer (NSCLC) and its correlation to oncogenic drivers. We retrospectively reviewed data of patients who underwent anatomic lung resection for NSCLC and whose mutational status was known, from 4 department of thoracic surgery, over the period 2008 to 2019. Primary endpoints were overall survival (OS) and time to recurrence (TTR). Clinical and molecular factors were investigated in the univariate and multivariate analysis for their association with the primary endpoints. RESULTS: 2027 patients were included in the analysis. Correlations between NLR and OS (R2=0.21), NLR and TTR (R2=0.085) were significant (P<0.0001), with corresponding Pearson R of -0.46 (P<0.0001) and -0.292 (P<0.001), respectively. ROC curve analysis defined NLR cut-off value at 4.07. In the univariable analysis, the median OS was 66 months (95% CI: 62.94 - 69.06) in case of pre-operative NLR ≤ 4.07 and 38 months (95% CI: 36.73 - 39.27) in case of pre-operative NLR > 4.07 (P<0.0001), with corresponding 5-y OS of 72% and 29% respectively. Median TTR was associated with pre-operative NLR. Median TTR was 25 months (95% CI: 21.52 - 28.48) in case of pre-operative NLR ≤ 4.07 and 17 months (95% CI: 16.04 - 17.96) in case of pre-operative NLR > 4.07 (P<0.0001), with corresponding 5-years TTR of 18% and 9% respectively. Significant correlations between NLR >4.07 and KRAS (Cramer's V = 0.082, P < 0.0001) and EGFR mutations (Cramer's V = 0.064, P = 0.004) were observed. CONCLUSIONS: Low pre-operative NLR is associated with longer OS in patients with resected NSCLC. Low pre-operative NLR is not associated with longer TTR in multivariate analysis. Correlation between the high NLR and KRAS/EGFR mutations were observed.
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Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , Linfócitos , Mutação/genética , Neutrófilos , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Período Pós-Operatório , Estudos RetrospectivosRESUMO
Renal cell carcinoma (RCC) remains a public health issue and seems to be increasing. A significant proportion of RCC patients will develop pulmonary metastasis at some point in their evolution. In this review, we aimed to update the surgical management of pulmonary metastases as well as systemic therapy, including targeted therapies, according to recent data in the literature. We retrospectively reviewed studies evaluating the benefit of pulmonary metastasectomy in RCC patients and evaluating the place of different chemotherapies, targeted therapies and immunotherapies through November 1, 2019. Several retrospective studies have shown the benefit of pulmonary metastasectomy in metastatic RCC (mRCC), most in a situation with only pulmonary metastases. According to the prognostic criteria of the IMDC risk model, the patient is classified into a prognostic group to identify the best systemic treatment. With the development of targeted therapies, the modalities are multiple and may involve tyrosine kinase inhibitors/checkpoint inhibitors and soon vaccine therapy or CAR-T cells. At the local level, in patients who cannot benefit from surgery, stereotactic radiotherapy or radiofrequency has a place to be considered. Although there is a lack of a randomized study, pulmonary metastasectomy appears to be feasible and effective. The place and modalities of systemic therapies in the era of targeted therapies remain to be more clearly defined.
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BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has decreased surgical activity, particularly in the field of oncology, because of the suspicion of a higher risk of COVID-19-related severe events. This study aimed to investigate the feasibility and safety of thoracic cancer surgery in the most severely affected European and Canadian regions during the COVID-19 pandemic. METHODS: The study investigators prospectively collected data on surgical procedures for malignant thoracic diseases from January 1 to April 30, 2020. The study included patients from 6 high-volume thoracic surgery departments: Nancy and Strasbourg (France), Freiburg (Germany), Milan and Turin (Italy), and Montreal (Canada). The centers involved in this research are all located in the most severely affected regions of those countries. An assessment of COVID-19-related symptoms, polymerase chain reaction (PCR)-confirmed COVID-19 infection, rates of hospital and intensive care unit admissions, and death was performed for each patient. Every deceased patient was tested for COVID-19 by PCR. RESULTS: In the study period, 731 patients who underwent 734 surgical procedures were included. In the whole cohort, 9 cases (1.2%) of COVID-19 were confirmed by PCR, including 5 in-hospital contaminants. Four patients (0.5%) needed readmission for oxygen requirements. In this subgroup, 2 patients (0.3%) needed intensive care unit and mechanical ventilatory support. The total number of deaths in the whole cohort was 22 (3%). A single death was related to COVID-19 (0.14%). CONCLUSIONS: Maintaining surgical oncologic activity in the era of the COVID-19 pandemic seems safe and feasible, with very low postoperative morbidity or mortality. To continue to offer the best care to patients who do not have COVID-19, reports on other diseases are urgently needed.
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COVID-19 , Neoplasias Torácicas/cirurgia , Procedimentos Cirúrgicos Torácicos , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Procedimentos Cirúrgicos Torácicos/efeitos adversosRESUMO
OBJECTIVES: Since video-assisted thoracic surgery (VATS) was first performed in the early 1990s, there have been many developments, and the conversion rate has decreased over the years. This article highlights the specific outcomes of patients undergoing conversion to thoracotomy despite initially scheduled VATS lung resection. METHODS: We retrospectively reviewed 501 patients who underwent thoracoscopic anatomic lung resection (i.e. lobectomy, segmentectomy or bilobectomy) between 1 January 2012 and 1 August 2017 at our institution. We explored the risk factors for surgical conversion and adverse events occurring in patients who underwent conversion to thoracotomy. RESULTS: A total of 44/501 patients underwent conversion during the procedure (global rate: 8.8%). The main reasons for conversion were (i) anatomical variation, adhesions or unexpected tumour extension (37%), followed by (ii) vascular causes (30%) and (iii) unexpected lymph node invasion (20%). The least common reason for conversion was technical failure (13%). We could not identify any specific risk factors for conversion. The global complication rate was significantly higher in converted patients (40.9%) than in complete VATS patients (16.8%) (P = 0.001). Postoperative atrial fibrillation was a major complication in converted patients (18.2%) [odds ratio (OR) 5.09, 95% confidence interval (CI) 1.80-13.27; P = 0.001]. Perioperative mortality was higher in the conversion group (6.8%) than in the VATS group (0.2%) (OR 33.3, 95% CI 3.4-328; P = 0.003). CONCLUSIONS: Through the years, the global conversion rate has dramatically decreased to <10%. Nevertheless, patients who undergo conversion represent a high-risk population in terms of complications (40.9% vs 16.8%) and perioperative mortality (6.8% vs 0.2%).
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Cirurgia Torácica Vídeoassistida/métodos , Toracotomia , Idoso , Humanos , Pulmão/cirurgia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Período Pós-Operatório , Estudos Retrospectivos , Fatores de RiscoAssuntos
Infecções por Coronavirus , Coronavirus , Neoplasias Pulmonares , Pandemias , Pneumonia Viral , Cirurgia Torácica , Betacoronavirus , COVID-19 , China , Humanos , Período Perioperatório , SARS-CoV-2RESUMO
Glioblastoma (GBM) is one of the most aggressive types of cancer, which begins within the brain. It is the most invasive type of glioma developed from astrocytes. Until today, Temozolomide (TMZ) is the only standard chemotherapy for patients with GBM. Even though chemotherapy extends the survival of patients, there are many undesirable side effects, and most cases show resistance to TMZ. FL3 is a synthetic flavagline which displays potent anticancer activities, and is known to inhibit cell proliferation, by provoking cell cycle arrest, and leads to apoptosis in a lot of cancer cell lines. However, the effect of FL3 in glioblastoma cancer cells has not yet been examined. Hypoxia is a major problem for patients with GBM, resulting in tumor resistance and aggressiveness. In this study, we explore the effect of FL3 in glioblastoma cells under normoxia and hypoxia conditions. Our results clearly indicate that this synthetic flavagline inhibits cell proliferation and induced senescence in glioblastoma cells cultured under both conditions. In addition, FL3 treatment had no effect on human brain astrocytes. These findings support the notion that the FL3 molecule could be used in combination with other chemotherapeutic agents or other therapies in glioblastoma treatments.
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Antineoplásicos/farmacologia , Astrócitos/efeitos dos fármacos , Benzofuranos/farmacologia , Neoplasias Encefálicas/tratamento farmacológico , Senescência Celular/efeitos dos fármacos , Glioblastoma/tratamento farmacológico , Aglaia/química , Anaerobiose/fisiologia , Apoptose/efeitos dos fármacos , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Glioblastoma/patologia , Humanos , Preparações de Plantas/farmacologiaRESUMO
Functional articular cartilage regeneration remains challenging, and it is essential to restore focal osteochondral defects and prevent secondary osteoarthritis. Combining autologous stem cells with therapeutic medical device, we developed a bi-compartmented implant that could promote both articular cartilage and subchondral bone regeneration. The first compartment based on therapeutic collagen associated with bone morphogenetic protein 2, provides structural support and promotes subchondral bone regeneration. The second compartment contains bone marrow-derived mesenchymal stem cell spheroids to support the regeneration of the articular cartilage. Six-month post-implantation, the regenerated articular cartilage surface was 3 times larger than that of untreated animals, and the regeneration of the osteochondral tissue occurred during the formation of hyaline-like cartilage. Our results demonstrate the positive impact of this combined advanced therapy medicinal product, meeting the needs of promising osteochondral regeneration in critical size articular defects in a large animal model combining not only therapeutic implant but also stem cells.
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Cartilagem Articular/crescimento & desenvolvimento , Transplante de Células-Tronco Mesenquimais , Osteocondrose/terapia , Próteses e Implantes , Regeneração/genética , Animais , Proteína Morfogenética Óssea 2/genética , Regeneração Óssea/genética , Regeneração Óssea/fisiologia , Cartilagem Articular/patologia , Colágeno/genética , Colágeno/farmacologia , Modelos Animais de Doenças , Humanos , Osteocondrose/genética , Osteocondrose/patologia , Ovinos/genética , Ovinos/fisiologia , Esferoides Celulares/citologia , Esferoides Celulares/transplante , Engenharia Tecidual/métodosRESUMO
BACKGROUND: Surgical repair has demonstrated a beneficial effect on outcome for patients presenting with flail chest or with multiple rib fractures. We hypothesized that benefit on outcome parameters concerns predominantly patients being extubated within 24 hours post-operatively. METHODS: We prospectively recorded all patients presenting with chest traumatism eligible for surgical repair with anticipated early extubation according to our institutional consensus (flail chest, major deformity, poor pain control, associated lesions requiring thoracotomy). We compared outcomes of patients extubated within 24 hours post-operatively to those who required prolonged ventilator support. We tested predictive factors for prolonged intubation with univariate and multivariate analysis. RESULTS: From 2010 to 2014, 132 patients required surgical repair. Two thirds were extubated within 24 hours following surgical repair. Pneumonia was the main complication and occurred in 30.3% of all patients. Patients extubated within 24 hours following surgical repair had significantly shorter ICU stay and shorter in-hospital stay (P<0.0001 both). Pneumonia occurred significantly more often in patients with longer mechanical ventilation (over 24 hours) (P<0.0001) and the overall post-operative complications rate was higher (P=0.0001). Main independent risk factors for delayed extubation were bilateral chest rib fractures and initially associated pneumothorax. CONCLUSIONS: We conclude that patients extubated within 24 hours after repair have an improved outcome with reduced complication rate and shorter hospital stay. The initial extent of the trauma is an important risk factor for delayed extubation and high complication rate despite surgical stabilization.