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1.
Cytopathology ; 33(1): 14-22, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34333812

RESUMO

There is growing evidence that molecular testing is feasible on all types of cytological preparation, which is fortunate as more diagnostic markers and biomarkers for targeted therapies are discovered for use in pulmonary and pleural malignancies. In this article we will discuss the pre-analytic, analytic, and post-analytic (interpretive) considerations for successful implementation of molecular tests for diagnostic and predictive markers in respiratory and pleural cytology. The vast majority of laboratories are familiar with, and have validated their molecular protocols for, formalin-fixed paraffin-embedded surgical specimens, which are not directly applicable to cytology specimens. Thus, rigorous validation must be performed for each type of fixative and cytology preparation before it is implemented in the clinical setting.


Assuntos
Neoplasias Pulmonares , Neoplasias Pleurais , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Citodiagnóstico , Humanos , Neoplasias Pulmonares/patologia , Pleura/patologia , Neoplasias Pleurais/diagnóstico , Neoplasias Pleurais/patologia
4.
Can Respir J ; 2022: 6763625, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36353447

RESUMO

The usage of bevacizumab for malignant pleural effusion (MPE) or malignant pericardial effusion (MPCE) has attracted increasing interest from researchers, but the precise ways of bevacizumab administration remain unknown. Patients with histologically or cytologically confirmed non-small-cell lung cancer (NSCLC) with MPE or MPCE were enrolled in the study and treated with a low dose of single bevacizumab (100 mg) intrapleurally or intrapericardially injected after the drainage of the effusions. The Lung Cancer Symptom Scale (LCSS), efficacy, and safety of drug administration were used as evaluation parameters in this study. The results indicated that lung cancer-related symptoms were significantly improved following treatment, compared with symptoms before the treatment (LCSS, score 494 ± 78 vs. score 377 ± 77, mean ± SD) (P < 0.001). Malignant effusions were well controlled, and the median time to progression (TTP) was 91 days and 111 days in MPE and MPCE, respectively. In addition, no severe side effects were observed, except in one patient with mild dizziness. In summary, the low dose of single bevacizumab (100 mg) with intrapleural or intrapericardial injection is effective and safe in the treatment of lung cancer-mediated malignant effusion, rapidly improving the malignant effusion-related symptoms and quality of life in patients with NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Derrame Pleural Maligno , Neoplasias Pleurais , Humanos , Derrame Pleural Maligno/tratamento farmacológico , Derrame Pleural Maligno/etiologia , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/tratamento farmacológico , Bevacizumab/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Qualidade de Vida
5.
J Biomed Opt ; 27(10)2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36316298

RESUMO

SignificanceDosimetry for photodynamic therapy is dependent on multiple parameters. Critically, in vivo tissue optical properties and hemodynamics must be determined carefully to calculate the total delivered light dose.AimSpectroscopic analysis of diffuse reflectance measurements of tissues taken during a clinical trial of 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a-mediated photodynamic therapy for pleural malignancies.ApproachDiffuse reflectance measurements were taken immediately before and after photodynamic therapy. Measurements were analyzed with a nonlinearly constrained multiwavelength, multi-distance algorithm to extract tissue optical properties, tissue oxygen saturation, StO2, and total hemoglobin concentration (THC).ResultsA total of 25 patients were measured, 23 of which produced reliable fits for optical property extraction. For all tissue types, StO2 ranged through [24, 100]% and [22, 97]% for pre-photodynamic therapy (PDT) and post-PDT conditions, respectively. Mean THC ranged through [ 69,152 ] µM and [ 48,111 ] µM, for pre-PDT and post-PDT, respectively. Absorption coefficients, µa, ranged through [ 0.024 , 3.5 ] cm - 1 and [ 0.039 , 3 ] cm - 1 for pre-PDT and post-PDT conditions, respectively. Reduced scattering coefficients, µs', ranged through [ 1.4 , 73.4 ] cm - 1 and [ 1.2 , 64 ] cm - 1 for pre-PDT and post-PDT conditions, respectively.ConclusionsThere were similar pre- and post-PDT tissue optical properties and hemodynamics. The high variability in each parameter for all tissue types emphasizes the importance of these measurements for accurate PDT dosimetry.


Assuntos
Fotoquimioterapia , Neoplasias Pleurais , Humanos , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Dronabinol , Neoplasias Pleurais/tratamento farmacológico , Hemodinâmica
6.
Int J Mol Sci ; 23(21)2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36362209

RESUMO

Pleural mesothelioma (PM) is a rare and aggressive disease that arises from the mesothelial cells lining the pleural cavity. Approximately 80% of PM patients have a history of asbestos exposure. The long latency period of 20-40 years from the time of asbestos exposure to diagnosis, suggests that multiple somatic genetic alterations are required for the tumorigenesis of PM. The genomic landscape of PM has been characterized by inter- and intratumor heterogeneity associated with the impairment of tumor suppressor genes such as CDKN2A, NF2, and BAP1. Current systemic therapies have shown only limited efficacy, and none is approved for patients with relapsed PM. Advances in understanding of the molecular landscape of PM has facilitated several biomarker-driven clinical trials but so far, no predictive biomarkers for targeted therapies are in clinical use. Recent advances in the PM genetics have provided optimism for successful molecular strategies in the future. Here, we summarize the molecular mechanism underlying PM pathogenesis and review potential therapeutic targets.


Assuntos
Amianto , Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurais , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/induzido quimicamente , Mesotelioma/tratamento farmacológico , Mesotelioma/genética , Mesotelioma/induzido quimicamente , Neoplasias Pleurais/tratamento farmacológico , Neoplasias Pleurais/genética , Amianto/efeitos adversos , Ubiquitina Tiolesterase/genética
7.
Intern Med ; 61(21): 3251-3257, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36328587

RESUMO

We performed endocytoscopy (ECS) for the ex vivo evaluation of mesothelioma in specimens biopsied during medical thoracoscopy in three patients. We evaluated 19 biopsy specimens based on the density of nuclei and irregularity in the nuclei shape using ECS and compared them with the histopathological findings. All 10 specimens considered malignant based on ECS were diagnosed as malignant based on histopathology. The nine specimens evaluated as non-malignant based on ECS consisted of six specimens diagnosed as malignant based on histopathology and three diagnosed as non-malignant based on histopathology. ECS was feasible and had some utility for ex vivo ultra-magnifying imaging of thoracoscopic biopsy specimens from patients with mesothelioma.


Assuntos
Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurais , Humanos , Mesotelioma/diagnóstico , Toracoscopia , Biópsia , Neoplasias Pleurais/diagnóstico
8.
Artigo em Inglês | MEDLINE | ID: mdl-36429481

RESUMO

Asbestos use started to be gradually banned in Europe from 1991 onwards, and there are currently strict occupational exposure limits for asbestos. However, malignant mesothelioma has a long latency time (in some cases up to 50-60 years), so the risks related to asbestos exposure should not be forgotten. Considering the increased risk of lung cancer following the inhalation of asbestos fibers, lifetime health monitoring should be considered in people occupationally exposed to asbestos, with an emphasis on the respiratory system. An assessment of their occupational history should be performed rigorously, especially in the areas with a history of asbestos production/use, as this is a key element for an early diagnosis and appropriate treatment. This case report presents a near-missed case of occupational pleural malignant mesothelioma. The latency time between the first asbestos exposure and the diagnosis of occupational pleural malignant mesothelioma was 49 years. The accurate diagnosis was made two years after the first symptoms appeared.


Assuntos
Amianto , Mesotelioma Maligno , Mesotelioma , Exposição Ocupacional , Neoplasias Pleurais , Humanos , Mesotelioma/induzido quimicamente , Mesotelioma/diagnóstico , Mesotelioma/terapia , Neoplasias Pleurais/diagnóstico , Neoplasias Pleurais/terapia , Neoplasias Pleurais/complicações , Amianto/efeitos adversos , Exposição Ocupacional/efeitos adversos
9.
Int J Mol Sci ; 23(19)2022 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-36233258

RESUMO

Malignant pleural mesothelioma (MPM) is a rare but aggressive thoracic malignancy with limited treatment options. One of the standard treatments for MPM is chemotherapy, which consists of concurrent treatment with pemetrexed and cisplatin. Pemetrexed limits tumor growth by inhibiting critical metabolic enzymes involved in nucleotide synthesis. Cisplatin causes direct DNA damage, such as intra-strand and inter-strand cross-links, which are repaired by the nucleotide excision repair pathway, which depends on relatively high nucleotide levels. We hypothesized that prolonged pretreatment with pemetrexed might deplete nucleotide pools, thereby sensitizing cancer cells to subsequent cisplatin treatment. The MPM cell lines ACC-MESO-1 and NCI-H28 were treated for 72 h with pemetrexed. Three treatment schedules were evaluated by initiating 24 h of cisplatin treatment at 0 h (concomitant), 24 h, and 48 h relative to pemetrexed treatment, resulting in either concomitant administration or pemetrexed pretreatment for 24 h or 48 h, respectively. Multicolor flow cytometry was performed to detect γH2AX (phosphorylation of histone H2AX), a surrogate marker for the activation of the DNA damage response pathway. DAPI staining of DNA was used to analyze cell cycle distribution. Forward and side scatter intensity was used to distinguish subpopulations based on cellular size and granularity, respectively. Our study revealed that prolonged pemetrexed pretreatment for 48 h prior to cisplatin significantly reduced long-term cell growth. Specifically, pretreatment for 48 h with pemetrexed induced a cell cycle arrest, mainly in the G2/M phase, accumulation of persistent DNA damage, and induction of a senescence phenotype. The present study demonstrates that optimizing the treatment schedule by pretreatment with pemetrexed increases the efficacy of the pemetrexed-cisplatin combination therapy in MPM. We show that the observed benefits are associated with the persistence of treatment-induced DNA damage. Our study suggests that an adjustment of the treatment schedule could improve the efficacy of the standard chemotherapy regimen for MPM and might improve patient outcomes.


Assuntos
Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Histonas , Humanos , Neoplasias Pulmonares/patologia , Mesotelioma/tratamento farmacológico , Mesotelioma/patologia , Nucleotídeos , Pemetrexede/farmacologia , Pemetrexede/uso terapêutico , Neoplasias Pleurais/tratamento farmacológico , Neoplasias Pleurais/patologia
10.
World J Surg Oncol ; 20(1): 350, 2022 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-36280841

RESUMO

BACKGROUND: Malignant peritoneal mesothelioma (MPM) is a rare malignant tumor with a high mortality rate and extremely poor prognosis. In-depth pathological analysis is essential to assess tumor biological behaviors and explore potential therapeutic targets of MPM. Nucleoplasmin 2 (NPM2) is a molecular chaperone that binds histones and may play a key role in the development and progression of tumors. This study aimed to analyze the correlation between the expression level of NPM2 and the main clinicopathological characteristics and prognosis of MPM. METHODS: Ninety-two postoperative specimens from MPM patients following cytoreductive surgery were collected. Postoperative specimens were stained with immunohistochemistry. The expression level of NPM2 was quantitatively analyzed by QuPath-0.3.2 software. Univariate and multivariate analyses were conducted to investigate the correlation between NPM2 expression and other conventional clinicopathological characteristics. RESULTS: Among the 92 MPM patients, there were 47 males (48.9%) and 45 females (51.1%), with a median age of 56 (range: 24-73). There were 70 (76.0%) cases with loss of NPM2 protein expression, 11 (12.0%) cases with low expression, and 11 (12.0%) cases with high expression. Univariate analysis showed that NPM2 protein expression level (negative vs. low expression vs. high expression) was negatively correlated with the following three clinicopathological factors: completeness of cytoreduction (CC) score, vascular tumor emboli, and serious adverse events (SAEs) (all P < 0.05). Multivariate analysis showed that NPM2 protein expression level (negative vs. low expression vs. high expression) was independently negatively correlated with the following two clinicopathological factors: CC score [odds ratio (OR) = 0.317, 95% CI: 0.317-0.959, P = 0.042] and vascular tumor emboli (OR = 0.092, 95% CI = 0.011-0.770, P = 0.028). Survival analysis showed that loss of NPM2 protein expression (negative vs. positive) was associated with poor prognosis of MPM. CONCLUSIONS: Loss of NPM2 expression is a potential immunohistochemical marker for MPM.


Assuntos
Neoplasias Pulmonares , Mesotelioma Maligno , Nucleoplasminas , Neoplasias Peritoneais , Neoplasias Pleurais , Neoplasias Vasculares , Feminino , Humanos , Masculino , Biomarcadores , Histonas , Neoplasias Pulmonares/diagnóstico , Mesotelioma Maligno/diagnóstico , Células Neoplásicas Circulantes , Nucleoplasminas/metabolismo , Neoplasias Peritoneais/diagnóstico , Neoplasias Pleurais/diagnóstico , Prognóstico , Neoplasias Vasculares/diagnóstico , Adulto , Pessoa de Meia-Idade , Idoso
11.
Medicine (Baltimore) ; 101(39): e30711, 2022 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-36181042

RESUMO

Malignant pleural mesothelioma (MPM) is an aggressive tumor with a poor prognosis. In our study, we aimed to investigate the specific clinical, laboratory, and radiological features of the tumor and the prognostic effect of SUVmax (maximum standardized uptake values) according to PET/CT (positron emission tomography). Demographic, therapeutic, clinical, and survival information of patients diagnosed with histologically-validated pleural mesothelioma in our hospital between January 2010 to December 2019 will be retrospectively scanned from the hospital records. A total of 116 patients, 61 men (52.6%), and 55 women (47.4%), were analyzed. Thirty five patients (30.2%) were over the age of 65. Percentage of patients over 65 years of age, neutrophil count, and PET SUV Max values, asbestos exposure and pleural thickening rate were significantly higher in the deceased patients' group than in the living patients' group (P = .042, P = .039, P = .002, P = .004, P = .037). T stage (tumor stage), N stage (lymph nodes stage), metastasis stage, and Grade distribution were significantly higher in the deceased patients' group than in the living patients' group (P < .000, P < .000, P = .003, P < .000). The rates of chemotherapy and surgical treatment, right lung location, and epithelioid pathology were significantly lower in the deceased patients' group compared to the living patients' group (P = .016, P = .030, P = .018, P = .008). The mean follow-up time was 13 months. Key determinants of survival in MPM include age, male gender, neutrophil increase, pleural thickening, high PET SUV max values, stage, histological type, asbestos exposure, and treatment regimen.


Assuntos
Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Doenças Pleurais , Neoplasias Pleurais , Feminino , Fluordesoxiglucose F18 , Humanos , Expectativa de Vida , Neoplasias Pulmonares/patologia , Masculino , Mesotelioma/diagnóstico , Neoplasias Pleurais/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Prognóstico , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
12.
BMJ Case Rep ; 15(10)2022 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-36207058

RESUMO

A woman in her early 70s was found to have incidental finger clubbing at a fracture clinic consultation for an unrelated problem. She reported no associated respiratory symptoms and was referred back to her General Practitioner for further investigation. A chest radiograph revealed a large left-sided mass. This was characterised as a pleural-based mass on CT, resulting in localised atelectasis and mediastinal shift. A CT guided biopsy revealed histology consistent with a solitary fibrous tumour of the pleura and the patient was referred for thoracotomy and resection.


Assuntos
Osteoartropatia Hipertrófica Secundária , Neoplasias Pleurais , Tumor Fibroso Solitário Pleural , Feminino , Humanos , Hipertrofia , Biópsia Guiada por Imagem , Osteoartropatia Hipertrófica Secundária/etiologia , Pleura/patologia , Neoplasias Pleurais/patologia , Tumor Fibroso Solitário Pleural/diagnóstico , Tumor Fibroso Solitário Pleural/diagnóstico por imagem , Tomografia Computadorizada por Raios X
13.
Clin Nucl Med ; 47(11): 980-981, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36215397

RESUMO

ABSTRACT: We describe 68 Ga-FAPI (fibroblast activation protein inhibitor)-04 and 18 F-FDG PET/CT findings in a case with epithelioid malignant pleural mesothelioma. Compared with 18 F-FDG PET/CT, 68 Ga-FAPI-04 PET/CT more clearly showed the pleural tumors and lymph node metastases and detected more pleural lesions because the tumors showed higher 68 Ga-FAPI-04 activity. This case indicates that 68 Ga-FAPI-04 PET/CT may be a promising new tool in evaluation of malignant pleural mesothelioma, which needs further investigation.


Assuntos
Mesotelioma Maligno , Neoplasias Pleurais , Fluordesoxiglucose F18 , Radioisótopos de Gálio , Humanos , Mesotelioma Maligno/diagnóstico por imagem , Neoplasias Pleurais/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Quinolinas
14.
PLoS One ; 17(10): e0275936, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36240245

RESUMO

Malignant pleural mesothelioma (MPM) is a cancer associated with asbestos exposure and its diagnosis is challenging due to the moderate sensitivities of the available methods. In this regard, miR-103a-3p was considered to increase the sensitivity of established biomarkers to detect MPM. Its behavior and diagnostic value in the Mexican population has not been previously evaluated. In 108 confirmed MPM cases and 218 controls, almost all formerly exposed to asbestos, we quantified miR-103-3a-3p levels in leukocytes using quantitative Real-Time PCR, together with mesothelin and calretinin measured in plasma by ELISA. Sensitivity and specificity of miR-103-3a-3p alone and in combination with mesothelin and calretinin were determined. Bivariate analysis was performed using Mann-Whitney U test and Spearman correlation. Non-conditional logistic regression models were used to calculate the area under curve (AUC), sensitivity, and specificity for the combination of biomarkers. Mesothelin and calretinin levels were higher among cases, remaining as well among males and participants ≤60 years old (only mesothelin). Significant differences for miR-103a-3p were observed between male cases and controls, whereas significant differences between cases and controls for mesothelin and calretinin were observed in men and women. At 95.5% specificity the individual sensitivity of miR-103a-3p was 4.4% in men, whereas the sensitivity of mesothelin and calretinin was 72.2% and 80.9%, respectively. Positive correlations for miR-103a-3p were observed with age, environmental asbestos exposure, years with diabetes mellitus, and glucose levels, while negative correlations were observed with years of occupational asbestos exposure, creatinine, erythrocytes, direct bilirubin, and leukocytes. The addition of miR-103a-3p to mesothelin and calretinin did not increase the diagnostic performance for MPM diagnosis. However, miR-103a-3p levels were correlated with several characteristics in the Mexican population.


Assuntos
Amianto , Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , MicroRNAs , Neoplasias Pleurais , Amianto/efeitos adversos , Bilirrubina , Biomarcadores Tumorais/genética , Calbindina 2/genética , Creatinina , Feminino , Proteínas Ligadas por GPI/genética , Glucose , Humanos , Leucócitos/patologia , Neoplasias Pulmonares/patologia , Masculino , Mesotelina , Mesotelioma/diagnóstico , Mesotelioma/genética , MicroRNAs/genética , Pessoa de Meia-Idade , Neoplasias Pleurais/patologia
15.
Int J Mol Sci ; 23(19)2022 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-36232554

RESUMO

Pleural mesothelioma (PM) is an aggressive cancer with poor prognosis and no effective therapies, mainly caused by exposure to asbestos. Antagonists of growth hormone-releasing hormone (GHRH) display strong antitumor effects in many experimental cancers, including lung cancer and mesothelioma. Here, we aimed to determine whether GHRH antagonist MIA-690 potentiates the antitumor effect of cisplatin and pemetrexed in PM. In vitro, MIA-690, in combination with cisplatin and pemetrexed, synergistically reduced cell viability, restrained cell proliferation and enhanced apoptosis, compared with drugs alone. In vivo, the same combination resulted in a strong growth inhibition of MSTO-211H xenografts, decreased tumor cell proliferation and increased apoptosis. Mechanistically, MIA-690, particularly with chemotherapeutic drugs, inhibited proliferative and oncogenic pathways, such as MAPK ERK1/2 and cMyc, and downregulated cyclin D1 and B1 mRNAs. Inflammatory pathways such as NF-kB and STAT3 were also reduced, as well as oxidative, angiogenic and tumorigenic markers (iNOS, COX-2, MMP2, MMP9 and HMGB1) and growth factors (VEGF and IGF-1). Overall, these findings strongly suggest that GHRH antagonists of MIA class, such as MIA-690, could increase the efficacy of standard therapy in PM.


Assuntos
Proteína HMGB1 , Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurais , Linhagem Celular Tumoral , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Ciclina D1 , Ciclo-Oxigenase 2 , Hormônio Liberador de Hormônio do Crescimento , Humanos , Fator de Crescimento Insulin-Like I/uso terapêutico , Metaloproteinase 2 da Matriz , Metaloproteinase 9 da Matriz/genética , Mesotelioma/tratamento farmacológico , Mesotelioma/patologia , NF-kappa B/metabolismo , Pemetrexede/farmacologia , Pemetrexede/uso terapêutico , Neoplasias Pleurais/tratamento farmacológico , Neoplasias Pleurais/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismo
16.
Artigo em Inglês | MEDLINE | ID: mdl-36205712

RESUMO

Although the diagnosis of malignant pleural mesothelioma at an in situ stage was traditionally challenging, it is now possible owing to advances in molecular biological methods such as P16 fluorescence in situ hybridization or BRCA1-associated protein 1 immunohistochemistry. Here, we report the first case, to our knowledge, of total parietal pleurectomy for mesothelioma in situ. Future follow-up and accumulation of cases are necessary to determine whether total parietal pleurectomy could be applied as a treatment for mesothelioma in situ or not.


Assuntos
Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurais , Humanos , Neoplasias Pleurais/diagnóstico por imagem , Neoplasias Pleurais/cirurgia , Hibridização in Situ Fluorescente , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirurgia , Mesotelioma/diagnóstico por imagem , Mesotelioma/cirurgia
17.
Clin Lung Cancer ; 23(8): 694-701, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36216742

RESUMO

BACKGROUND: Optimal therapy for malignant pleural mesothelioma (MPM) remains unclear. We compared overall survival in patients with MPM after various multimodal treatment regimens including combinations of immunotherapy, chemotherapy, and surgery. PATIENTS AND METHODS: We examined MPM patients treated within our integrated health system from January 1, 2009 to December 31, 2020. Patients were grouped based on treatment regimen: chemotherapy alone (CT), immunotherapy with or without chemotherapy (iCT), surgery with chemotherapy (sCT), and surgery with immunotherapy and chemotherapy (siCT). We analyzed baseline characteristics and overall patient survival among these groups and several subgroups. RESULTS: One hundred seventy-nine patients were included. Among the study groups, there was no difference in age, sex, race/ethnicity, Charlson Comorbidity Index, or Eastern Cooperative Oncology Group performance status. Patients treated with CT (N = 109), iCT (N = 35), sCT (N = 26), and siCT (N = 9) had median (95% confidence interval) survivals of 11.7 (9.9-16.3), 18.2 (14.5-29.8), 20.7 (11.6-37.2), and 22.6 (19.7-37.8) months, respectively (P < .001). Median survival among patients with and without immunotherapy was 19.7 (17.4-29.8) and 12.3 (10.6-17.3) months, respectively (P = .023). Median survival among patients with and without surgery was 21.7 (17.6-34.8) and 13.6 (11.5-17.3) months, respectively (P = .007). Patients with biphasic/sarcomatoid subtypes who received immunotherapy experienced 76.2% (55.8%-100.0%) 12 month survival vs. 13.6% (4.8%-39.0%) among those who did not (P < .001). CONCLUSION: MPM patients receiving surgery and immunotherapy as part of multimodal treatment regimens experienced the longest survival. Surgery and immunotherapy are each associated with survival. Further investigations are warranted to assess the benefit of immunotherapy within multimodal treatment regimens for MPM.


Assuntos
Prestação Integrada de Cuidados de Saúde , Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurais , Humanos , Neoplasias Pleurais/patologia , Neoplasias Pulmonares/tratamento farmacológico , Terapia Combinada
18.
Med Lav ; 113(5): e2022047, 2022 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-36282034

RESUMO

BACKGROUND: The aim of this study is to describe the incidence of malignant mesothelioma (MM) and asbestos exposure in an Italian region in the period 1996-June 2021. METHODS: The study included cases with microscopic confirmation and those with instrumental confirmation. For each case, information on sex, age, tumour site, morphology and date of diagnosis was collected, along with details of exposure to asbestos. RESULTS: 3,097 cases of MM (2,233 males and 864 females) were registered: 90.8% with microscopic confirmation. A total of 2,840 cases involved the pleura (92%), 230 cases the peritoneum (7%), and a small number of cases the pericardium and testis (9 and 18, respectively). Most cases (78.0%) occurred after 65 years of age, while only 1.5% concerned individuals with age < 45 years. The standardized incidence rate for the entire period (adjusted to the 2000 Italian standard population and calculated per 100,000 person-years) was equal to 3.9 in males and 1.4 in females, and the trend showed an increase with age in both sexes. Concerning asbestos exposure, 79.7% of cases were exposed (86.7% males and 60.1% females). In 70.3%, exposure was occupational (83.4% males and 33.2% females), while 20.7% of females and 0.8% of males had familial exposure. Building construction, rolling stock manufacture/repair and metalworking were the most prevalent economic activities associated with occupational exposure. CONCLUSIONS: This study offers an overview of MM in an Italian region characterized by high incidence and high exposure due to its particular production activities.


Assuntos
Amianto , Mesotelioma Maligno , Mesotelioma , Exposição Ocupacional , Neoplasias Pleurais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Amianto/efeitos adversos , Incidência , Itália/epidemiologia , Mesotelioma/epidemiologia , Mesotelioma/etiologia , Exposição Ocupacional/efeitos adversos , Neoplasias Pleurais/epidemiologia , Neoplasias Pleurais/etiologia
19.
Med. clín (Ed. impr.) ; 159(5): 240-247, septiembre 2022. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-208980

RESUMO

El diagnóstico de mesotelioma pleural difuso requiere en la mayoría de los casos una biopsia pleural, realizada bajo control de imagen (ecografía o tomografía computarizada) o mediante toracoscopia. La pérdida de expresión de BAP1 o de MTAP (inmunohistoquímica) y la deleción homocigota de CDKN2A (hibridación fluorescente in situ) constituyen los marcadores moleculares básicos para el diagnóstico de mesotelioma. El tipo histológico y el estado funcional del paciente son los factores pronósticos más importantes. El control del derrame pleural se puede realizar a través de la inserción de catéteres pleurales tunelizados, bien como medida aislada (p. ej. pacientes no susceptibles de terapia multimodal que se han diagnosticado por citología del líquido pleural o biopsia guiada por imagen) o combinada con la administración de talco aerosolizado durante una toracoscopia diagnóstica. La inmunoterapia constituye una de las primeras líneas de tratamiento en pacientes inoperables, particularmente en las variedades histológicas bifásicas o sarcomatosas. (AU)


The diagnosis of diffuse pleural mesothelioma requires in most cases a pleural biopsy, performed either under imaging guidance (ultrasound or computed tomography) or thoracoscopy. Loss of BAP1 or MTAP expression (immunohistochemistry) and homozygous deletion of CDKN2A (fluorescence in situ hybridization) are the basic molecular markers for the diagnosis of mesothelioma. The histologic type and patient's performance status are the most important prognostic factors. Pleural effusion can be managed by the insertion of tunneled pleural catheters, either as a stand-alone measure (e.g., patients not amenable to multimodality therapy who have been diagnosed by pleural fluid cytology or image-guided biopsy) or combined with the administration of aerosolized talc during a diagnostic thoracoscopy. Immunotherapy is one of the front-line approaches in inoperable patients, particularly in biphasic or sarcomatous histologic varieties. (AU)


Assuntos
Humanos , Biomarcadores Tumorais/metabolismo , Homozigoto , Hibridização In Situ , Fluorescência , Neoplasias Pleurais/diagnóstico , Neoplasias Pleurais/genética , Neoplasias Pleurais/terapia , Mesotelioma/diagnóstico , Mesotelioma/genética , Mesotelioma/terapia , Ubiquitina Tiolesterase/genética , Ubiquitina Tiolesterase/metabolismo , Deleção de Sequência
20.
Semin Cancer Biol ; 86(Pt 2): 93-100, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36096316

RESUMO

The energy metabolism of tumor cells is considered one of the hallmarks of cancer because it is different from normal cells and mainly consists of aerobic glycolysis, fatty acid oxidation, and glutaminolysis. It is about one hundred years ago since Warburg observed that cancer cells prefer aerobic glycolysis even in normoxic conditions, favoring their high proliferation rate. A pivotal enzyme driving this phenomenon is lactate dehydrogenase (LDH), and this review describes prognostic and therapeutic opportunities associated with this enzyme, focussing on tumors with limited therapeutic strategies and life expectancy (i.e., pancreatic and thoracic cancers). Expression levels of LDH-A in pancreatic cancer tissues correlate with clinicopathological features: LDH-A is overexpressed during pancreatic carcinogenesis and showed significantly higher expression in more aggressive tumors. Similarly, LDH levels are a marker of negative prognosis in patients with both adenocarcinoma or squamous cell lung carcinoma, as well as in malignant pleural mesothelioma. Additionally, serum LDH levels may play a key role in the clinical management of these diseases because they are associated with tissue damage induced by tumor burden. Lastly, we discuss the promising results of strategies targeting LDH as a treatment strategy, reporting recent preclinical and translational studies supporting the use of LDH-inhibitors in combinations with current/novel chemotherapeutics that can synergistically target the oxygenated cells present in the tumor.


Assuntos
Metabolismo Energético , Lactato Desidrogenase 5 , Neoplasias Pancreáticas , Neoplasias Torácicas , Humanos , Glicólise/fisiologia , Isoenzimas/metabolismo , L-Lactato Desidrogenase/metabolismo , Lactato Desidrogenase 5/biossíntese , Neoplasias Pulmonares/metabolismo , Neoplasias Pancreáticas/metabolismo , Mesotelioma/metabolismo , Neoplasias Pleurais/metabolismo , Neoplasias Torácicas/metabolismo
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