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1.
Z Gastroenterol ; 58(2): 146-151, 2020 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-32050285

RESUMO

Diffuse malignant peritoneal mesothelioma (DMPM) is a rare diagnosis, found more frequently in men than in women. Symptoms are unspecific abdominal disorders making that diagnosis difficult to set. Causes of DMPM are yet to be discovered in entirety. Asbestos exposure is the reason for approximately 7 % of all peritoneal mesotheliomas. Until the evaluation of systematic cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) DMPM was a fatal diagnosis with a median overall survival (OS) of 4-13 months. The prognosis of DMPM dramatically improved with implementation of CRS and HIPEC to an OS of 30-92 month nowadys. CRS and HIPEC were performed in this case.


Assuntos
Antineoplásicos/administração & dosagem , Procedimentos Cirúrgicos de Citorredução , Hipertermia Induzida/métodos , Mesotelioma/terapia , Neoplasias Peritoneais/terapia , Protocolos de Quimioterapia Combinada Antineoplásica , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução/métodos , Feminino , Humanos , Masculino , Mesotelioma/tratamento farmacológico , Mesotelioma/mortalidade , Mesotelioma/cirurgia , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/cirurgia , Prognóstico , Taxa de Sobrevida
2.
Rev. Asoc. Méd. Argent ; 132(4): 15-19, dic. 2019. ilus
Artigo em Espanhol | LILACS | ID: biblio-1087168

RESUMO

El mesotelioma difuso es una neoplasia maligna poco frecuente que proviene de las células mesoteliales; la pleura es su localización más habitual y se estima que un 10% de los casos se localizan a nivel peritoneal. El mesotelioma es habitualmente diagnosticado en la quinta década de la vida, con un claro predominio en el sexo masculino, debido esto último a su relación con la exposición laboral al asbesto. Se expone un caso con factores de riesgo y diagnóstico asociado. (AU)


Diffuse mesothelioma is a rare malignant neoplasm that comes from mesothelial cells; the pleura are the most common location and is estimated that 10% of the cases are located at the peritoneal level. Mesothelioma is usually diagnosed in the fifth decade of life, with a clear predominance in the male sex, due to its relation to occupational exposureto asbestos. A case is presented with risk factors and associated diagnosis. (AU)


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pleurais/diagnóstico por imagem , Tomografia Computadorizada Multidetectores , Mesotelioma/etiologia , Mesotelioma/diagnóstico por imagem , Asbestos/efeitos adversos , Diagnóstico Diferencial , Mesotelioma/terapia , Estadiamento de Neoplasias
3.
Anticancer Res ; 39(11): 6241-6247, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704853

RESUMO

BACKGROUND/AIM: We performed multimodality therapy comprising preoperative chemotherapy, extrapleural pneumonectomy (EPP), and radiation therapy for patients with malignant pleural mesothelioma (MPM). Although multimodality therapy resulted in good prognosis, further improvement is required. Therefore, herein, we analysed the prognostic factors using surgical specimens and searched for suitable molecular targets to improve the prognosis after multidisciplinary treatment. PATIENTS AND METHODS: Forty-six patients with MPM underwent multimodality therapy. Paraffin-embedded surgical samples were used for immunohistochemistry to evaluate the expression of phosphorylated (p-) AKT, extracellular signal-regulated kinase (ERK), mammalian target of rapamycin (mTOR), mitogen-activated protein kinase (MAPK), eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), and S6 ribosomal protein (S6RP). RESULTS: On univariate and multivariate analyses, significant differences were observed according to the histological type, pathological stage, and p-mTOR expression rate. CONCLUSION: The prognosis of MPM is affected by p-mTOR expression, suggesting that molecular-targeted treatment might be used during multimodal therapy for MPM.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias Pulmonares/enzimologia , Mesotelioma/enzimologia , Proteína Quinase 1 Ativada por Mitógeno/análise , Neoplasias Pleurais/enzimologia , Serina-Treonina Quinases TOR/análise , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/metabolismo , Cisplatino/administração & dosagem , Terapia Combinada/métodos , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/terapia , Masculino , Mesotelioma/mortalidade , Mesotelioma/terapia , Pessoa de Meia-Idade , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Terapia de Alvo Molecular , Pemetrexede/administração & dosagem , Neoplasias Pleurais/mortalidade , Neoplasias Pleurais/terapia , Pneumonectomia , Prognóstico , Proteínas Serina-Treonina Quinases/análise , Proteínas Serina-Treonina Quinases/metabolismo , Serina-Treonina Quinases TOR/metabolismo
4.
J Surg Oncol ; 120(7): 1220-1226, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31602673

RESUMO

BACKGROUND AND OBJECTIVES: Hyperthermic intrathoracic chemotherapy (HITOC) is used for the treatment of malignant pleural tumors. Although HITOC proved to be safe, postoperative renal failure due to nephrotoxicity of intrapleural cisplatin remains a concern. METHODS: This single-center study was performed retrospectively in patients who underwent pleural tumor resection and HITOC between September 2008 and December 2018. RESULTS: A total of 84 patients (female n = 33; 39.3%) with malignant pleural tumors underwent surgical cytoreduction with subsequent HITOC (60 minutes; 42°C). During the study period, we gradually increased the dosage of cisplatin (100-150 mg/m2 BSA n = 36; 175 mg/m2 BSA n = 2) and finally added doxorubicin (cisplatin 175 mg/m2 BSA/doxorubicin 65 mg; n = 46). All patients had perioperative fluid balancing. The last 54 (64.3%) patients also received perioperative cytoprotection. Overall 29 patients (34.5%) experienced renal insufficiency. Despite higher cisplatin concentrations, patients with cytoprotection showed significantly lower postoperative serum creatinine levels after 1 week (P = .006) and at discharge (P = .020). Also, they showed less intermediate and severe renal insufficiencies (5.6% vs 13.3%). CONCLUSIONS: Adequate perioperative fluid management and cytoprotection seem to be effective in protecting renal function. This allows the administration of higher intracavitary cisplatin doses without raising the rate of renal insufficiencies.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimioterapia do Câncer por Perfusão Regional/efeitos adversos , Hipertermia Induzida/efeitos adversos , Mesotelioma/terapia , Néfrons/efeitos dos fármacos , Neoplasias Pleurais/terapia , Substâncias Protetoras/administração & dosagem , Insuficiência Renal Crônica/tratamento farmacológico , Amifostina/administração & dosagem , Cisplatino/administração & dosagem , Terapia Combinada , Creatinina/sangue , Citoproteção , Doxorrubicina/administração & dosagem , Feminino , Seguimentos , Humanos , Masculino , Mesotelioma/patologia , Pessoa de Meia-Idade , Neoplasias Pleurais/patologia , Cuidados Pós-Operatórios , Prognóstico , Insuficiência Renal Crônica/induzido quimicamente , Insuficiência Renal Crônica/patologia , Estudos Retrospectivos , Taxa de Sobrevida , Tiossulfatos/administração & dosagem , Cavidade Torácica/cirurgia
5.
Anticancer Res ; 39(9): 5219-5223, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519636

RESUMO

AIM: This study evaluated the prognostic value of soluble mesothelin-related protein (SMRP) levels in pleural effusions (PE) from patients with pleural mesothelioma (MPM). PATIENTS AND METHODS: SMRP level in PE was tested using an enzyme-linked immunosorbent assay (ELISA) in 109 patients with MPM at diagnosis before any treatment. The Kaplan-Meier method and the Cox regression were applied to compare overall survival probabilities across tertile categories of SMRP level. RESULTS: No significant differences in Kaplan-Meier overall survival probabilities among the SMRP categories were found. A statistically non-significant trend for increased death rate ratio (RR) was computed (p=0.327) when the higher (>46.5 nM, RR=1.38) and intermediate (8.5-46.5 nM, RR=1.18) SMRP categories were compared to the lower category (<8.5 nM, RR=1.00). Cox regression modelling including a restricted cubic spline showed a moderately rising non-linear trend in death rate. CONCLUSION: The SMRP level in PE does not appear to have prognostic significance and its detection is not recommended in routine clinical management of patients with MPM.


Assuntos
Proteínas Ligadas por GPI/metabolismo , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/mortalidade , Mesotelioma/complicações , Mesotelioma/mortalidade , Derrame Pleural Maligno/etiologia , Derrame Pleural Maligno/metabolismo , Neoplasias Pleurais/complicações , Neoplasias Pleurais/mortalidade , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Masculino , Mesotelioma/diagnóstico , Mesotelioma/terapia , Pessoa de Meia-Idade , Derrame Pleural Maligno/diagnóstico , Derrame Pleural Maligno/terapia , Neoplasias Pleurais/diagnóstico , Neoplasias Pleurais/terapia , Prognóstico , Curva ROC , Resultado do Tratamento
6.
Int J Mol Sci ; 20(17)2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31455014

RESUMO

In light of the promising results of immune checkpoint blockade (ICPB) in malignant pleural mesothelioma (MPM), we investigated the effect of different chemotherapeutic agents on the expression of immune checkpoints (ICPs) in order to rationally design a good treatment schedule for their combination with ICP blocking antibodies. Cisplatin, oxaliplatin and pemetrexed are interesting chemotherapeutic agents to combine with immunotherapy given their immunomodulatory capacities. We looked into cisplatin and pemetrexed because their combination is used as first-line treatment of MPM. Additionally, the effect of the immunogenic chemotherapeutic agent, oxaliplatin, was also studied. Three different MPM cell lines were used for representation of both epithelioid and sarcomatoid subtypes. The desired inhibitory concentrations of the chemotherapeutic agents were determined with the SRB-assay. Allogeneic co-cultures of MPM cells with healthy donor peripheral blood mononuclear cells (PBMC) were set up to assess the effect of these chemotherapeutic agents on the expression of ICPs (PD-1, LAG-3, TIM-3) and their ligands (PD-L1, PD-L2, galectin-9). Cisplatin might be a promising treatment to combine with ICP blocking antibodies since our MPM cell lines were most susceptible to this stand-alone treatment. We found that the expression of ICPs and their ligands on both MPM cells and PBMC was mostly downregulated or unaltered when treated with chemotherapeutic agents, though no clear trend could be determined.


Assuntos
Antineoplásicos Imunológicos/farmacologia , Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/metabolismo , Mesotelioma/etiologia , Mesotelioma/metabolismo , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores Tumorais/antagonistas & inibidores , Linhagem Celular Tumoral , Terapia Combinada , Expressão Gênica , Humanos , Imunomodulação/efeitos dos fármacos , Imunoterapia/métodos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Mesotelioma/patologia , Mesotelioma/terapia , Terapia de Alvo Molecular , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia
7.
J Surg Oncol ; 120(4): 794-802, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31309588

RESUMO

BACKGROUND AND OBJECTIVES: To review long-term survival outcomes of patients with Peritoneal metastasis (PM) who underwent colorectal cancer (CRS) and intraperitoneal chemotherapy (PIC). METHODS: Patients that underwent CRS, with or without PIC, from January 1996 to March 2018 at the Peritonectomy Unit of St. George Hospital, Sydney were retrospectively analyzed from a prospectively maintained database. RESULTS: The study comprised of 1225 cases, including 687 females (56.1%) and 538 males (43.9%). Diagnoses included CRC (n = 363), followed by HAMN (n = 317), LAMN (n = 297), mesothelioma (n = 101), ovarian cancer (n = 55), and others including gastric, sarcoma, and neuroendocrine tumor (n = 92). The median OS, 5- and 10-year survivals for CRC were 35 months, 33% and 8%, respectively. Patients with LAMN, in relative to HAMN, experienced a higher median OS, 5- and 10-year survivals (248 months vs 63 months; 82% vs 52% and 59% vs 28%). The median OS for mesothelioma was 60 months with 5- and 10-year survivals of 48% and 19%, respectively. In ovarian cancer, the median OS was 30 months with 5- and 10-year survivals of 26% and 10%, respectively. For the remaining histological diagnoses, median OS and 5-year survival were 28 months and 27%, respectively. CONCLUSION: Our large-cohort data showed that CRS/PIC can provide long-term survival benefit to patients with PM of gastrointestinal and ovarian origin.


Assuntos
Neoplasias do Apêndice/mortalidade , Quimioterapia do Câncer por Perfusão Regional/mortalidade , Neoplasias Colorretais/mortalidade , Procedimentos Cirúrgicos de Citorredução/mortalidade , Neoplasias Pulmonares/mortalidade , Mesotelioma/mortalidade , Neoplasias Ovarianas/mortalidade , Neoplasias Peritoneais/mortalidade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Apêndice/patologia , Neoplasias do Apêndice/terapia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/terapia , Terapia Combinada , Feminino , Seguimentos , Humanos , Injeções Intraperitoneais , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Masculino , Mesotelioma/patologia , Mesotelioma/terapia , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , Assistência Perioperatória , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/terapia , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Taxa de Sobrevida
8.
Am Soc Clin Oncol Educ Book ; 39: 543-552, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31099677

RESUMO

The introduction of programmed death receptor ligand-1 (PD-L1) and programmed death receptor-1 (PD-1) inhibitors into the field of non-small cell lung cancer (NSCLC) was practice changing. The pivotal trials consistently showed a clinically meaningful improvement in overall survival (OS) for patients with driver mutation-negative NSCLC, a field in which outcomes had been stagnant for decades. The success of immune checkpoint inhibitor (ICI) therapy in NSCLC has led to enthusiasm to expand the reach of these drugs into other thoracic malignancies such as thymic epithelial tumors (TETs), mesothelioma, and small cell lung cancer (SCLC). Unfortunately, the improvement in outcomes with ICI therapy in these rarer thoracic tumors has been somewhat modest, and in the case of thymoma, rates of adverse events are too high to routinely justify their use. Although the response rates seen in ICI therapy in these tumor types are similar to those seen with other available single-agent therapies for advanced disease, ICIs do present another option for clinicians treating patients with mesothelioma, small cell carcinoma, and thymic carcinoma (TC), diseases in which approved treatment options are limited. Here we review the latest trials of ICI therapy in mesothelioma, SCLC, and TETs.


Assuntos
Imunoterapia , Neoplasias Pulmonares/terapia , Mesotelioma/terapia , Neoplasias Epiteliais e Glandulares/terapia , Carcinoma de Pequenas Células do Pulmão/terapia , Neoplasias do Timo/terapia , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ensaios Clínicos como Assunto , Gerenciamento Clínico , Humanos , Imunoterapia/efeitos adversos , Imunoterapia/métodos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/imunologia , Mesotelioma/diagnóstico , Mesotelioma/imunologia , Neoplasias Epiteliais e Glandulares/diagnóstico , Neoplasias Epiteliais e Glandulares/imunologia , Recidiva , Terapia de Salvação , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Carcinoma de Pequenas Células do Pulmão/imunologia , Neoplasias do Timo/diagnóstico , Neoplasias do Timo/imunologia
9.
Support Care Cancer ; 27(12): 4675-4686, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30944991

RESUMO

BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare cancer with poor prognosis. As there is little information on the lived experience of MPM, our aim was to document the experience of MPM patients and their caregivers. METHODS: Surveys for MPM patients and caregivers were developed from previous interviews with patients, caregivers, and health professionals, about treatments and decision-making. Participants were recruited from two hospitals, government compensation body, and support groups. RESULTS: Survey responses were received from 78 MPM patients and 106 caregivers from January to September 2014. PATIENTS: 85% male, median age 69 years, median time since diagnosis 15 months. Caregivers: median age 68, 91% female, 90% spouse of MPM patient, 95% bereaved. Most participants felt informed about treatment options but only 69% thought all treatment options were discussed. Chemotherapy was discussed most frequently (92-95%); ~80% had sufficient information for decision-making. Decision regarding chemotherapy was made by patient considering doctor's opinion (24%), doctor and patient equally (18%), and doctor (17%). Participants 'agreed'/'strongly agreed' that they made the right decision about chemotherapy (patients 81%, caregivers 60%), but 5% and 16%, respectively, regretted the decision. Most participants received 'sufficient' support (71%). A quarter reported seeing cancer nurse specialists. Palliative care referral: 31% patients, 85% caregivers. Caregivers would have liked to talk to someone by themselves (41%), more time with doctors (30%), psychological support (29%), and clearer information (31%). Bereaved caregivers requested grief counselling (39%) and post-death consultation with specialists (23-25%). CONCLUSIONS: Satisfaction with treatment was high, but participants identified need for improved communication and quality information, discussion about all treatments, end-of-life assistance, and caregiver support after the patient's death.


Assuntos
Cuidadores/psicologia , Pessoal de Saúde/psicologia , Neoplasias Pulmonares/psicologia , Neoplasias Pulmonares/terapia , Mesotelioma/psicologia , Mesotelioma/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Tomada de Decisões , Feminino , Pesar , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos/métodos , Relações Médico-Paciente , Inquéritos e Questionários
10.
Ann Surg Oncol ; 26(8): 2357-2366, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31011908

RESUMO

BACKGROUND: The median age at diagnosis for malignant pleural mesothelioma (MPM) is approximately 72 years. Elderly patients pose unique management challenges because of the increased risk of therapy-related toxicities and mortality. Because there are no high-volume retrospective studies, prospective trials, or dedicated treatment recommendations for this population, this investigation addresses a major knowledge gap by examining national practice patterns and postoperative/survival outcomes in elderly MPM patients. METHODS: The National Cancer Database was queried for patients aged ≥ 80 years with newly diagnosed nonmetastatic MPM. Multivariable logistic regression ascertained factors associated with observation and surgery. Kaplan-Meier analysis assessed overall survival (OS), and multivariable Cox proportional hazards modeling examined factors associated with OS. Survival was also calculated following propensity matching. Additionally, postoperative outcomes were evaluated in surgical patients. RESULTS: Of 4526 patients, 2% received surgery and chemotherapy, 22% underwent chemotherapy alone, and 63% were observed. Respective median OS was 12.2, 9.5, and 4.1 months (p < 0.001). Differences between all groups persisted following propensity matching (all comparisons p < 0.05). For the 8% of patients who underwent specified definitive surgery (95% of whom received pleurectomy/decortication), 30- and 90-day mortality rates were 11.0% and 28.5%, respectively. The median length of postoperative hospitalization was 6 days, with 30-day readmission occurring in 7.5% of patients. CONCLUSIONS: The majority of elderly MPM patients in the US are observed, which was associated with poorer OS than chemotherapy and/or surgery. Although highly selected surgery/chemotherapy patients were associated with the longest OS, given the high biases in database studies and high perioperative mortality rates, careful patient selection for combined modality approaches in this population is imperative.


Assuntos
Bases de Dados Factuais , Neoplasias Pulmonares/terapia , Mesotelioma/terapia , Neoplasias Pleurais/terapia , Idoso de 80 Anos ou mais , Terapia Combinada , Gerenciamento Clínico , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/patologia , Masculino , Mesotelioma/patologia , Neoplasias Pleurais/patologia , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Taxa de Sobrevida
11.
Ann Thorac Surg ; 108(3): 889-896, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31004585

RESUMO

BACKGROUND: Current guidelines support cancer-directed surgery, chemotherapy, or active surveillance for clinical stages 1 to 3 of epithelial malignant pleural mesothelioma (MPM). Definitive chemotherapy is recommended for sarcomatoid/biphasic histologies. Our objective is to assess compliance with recommendations, measuring their impact on overall survival. METHODS: The National Cancer Database participant user file (2004 to 2014) was queried for patients diagnosed with MPM clinical stages 1 to 3. Multivariable logistic regression model identified factors independently associated with guideline compliance. Kaplan-Meier analysis and Cox proportional hazards were used for overall survival comparison with histologic subgroup analysis. RESULTS: A total of 3419 patients with clinical stages 1 to 3 met criteria for analysis and comprised epithelial (68.5%), sarcomatoid (17.2%), and biphasic subtypes (14.3%). Cancer-directed surgery was significantly underutilized in epithelial MPM, with 29.3% having no treatment. On multivariable analysis, insurance status and facility type were the strongest predictors of guideline compliance. High-volume hospitals were the most compliant with guidelines (odds ratio 3.58, 95% confidence interval (CI), 2.34 to 5.49, P < .001). Median survival estimates for no treatment, chemotherapy alone, surgery plus chemotherapy, and trimodal therapy were 10.2, 15.4, 21.1, and 21.7 months, respectively (log rank P < .001). In epithelial MPM, a significant increase in overall survival was observed in surgery plus chemotherapy (hazard ratio 0.62, 95% CI, 0.53 to 0.73, P < .001) and trimodality (hazard ratio 0.61, 95% CI, 0.49 to 0.76, P < .001; reference: no treatment). CONCLUSIONS: There is a suboptimal compliance with national guidelines for the treatment of MPM, particularly in low-volume nonacademic settings. Adherence to recommended surgery-based multimodal therapy is associated with an overall survival improvement.


Assuntos
Causas de Morte , Disparidades em Assistência à Saúde , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/terapia , Mesotelioma/mortalidade , Mesotelioma/terapia , Neoplasias Pleurais/mortalidade , Neoplasias Pleurais/terapia , Adulto , Idoso , California , Estudos de Coortes , Terapia Combinada , Bases de Dados Factuais , Intervalo Livre de Doença , Feminino , Fidelidade a Diretrizes , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/diagnóstico , Masculino , Mesotelioma/diagnóstico , Pessoa de Meia-Idade , Neoplasias Pleurais/diagnóstico , Pneumonectomia/métodos , Guias de Prática Clínica como Assunto , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida
12.
J BUON ; 24(1): 391-396, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30941996

RESUMO

PURPOSE: Peritoneal mesothelioma is a rare disease that remains confined to the peritoneal surfaces for long. Cytoreductive surgery (CRS) combined with hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) is the most effective treatment and complete cytoreduction is the most significant prognostic indicator of long-term survival. This study attempted to present the results of CRS in combination with hyperthermic intraperitoneal chemotherapy in patients with peritoneal mesothelioma and identify the prognostic indicators of survival. METHODS: The files of patients with peritoneal mesothelioma were retrospectively reviewed. Morbidity, hospital mortality, recurrences, and the sites of recurrence were recorded. Survival and recurrence were correlated to performance status, age, extent of peritoneal dissemination, tumor grade, tumor volume, and completeness of cytoreduction. RESULTS: From 2005-2017, 29 patients underwent 33 cytoreductions for peritoneal mesothelioma. Hospital mortality and morbidity were 3% and 27.3% respectively. The median and 8-year survival were 66 and 62% months, respectively. The completeness of cytoreduction was the single prognostic indicator of survival, and the tumor grade the single prognostic indicator of recurrence. CONCLUSION: CRS combined with HIPEC is the therapeutic strategy that may provide long-term survival.


Assuntos
Mesotelioma/terapia , Neoplasias Peritoneais/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução/métodos , Feminino , Humanos , Hipertermia Induzida/métodos , Cuidados Intraoperatórios/métodos , Masculino , Mesotelioma/mortalidade , Mesotelioma/patologia , Pessoa de Meia-Idade , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/patologia , Estudos Retrospectivos , Análise de Sobrevida , Adulto Jovem
13.
Gan To Kagaku Ryoho ; 46(2): 395-399, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30914572

RESUMO

BACKGROUND AND OBJECTIVES: The current standard of treatment for malignant peritoneal mesothelioma(MPM)is cytoreductive surgery(CRS)plus perioperative intraperitoneal or systemic chemotherapy(comprehensive treatment), The present study was performed to clarify the prognostic factors of PMP after comprehensive treatment. METHODS: Among 63 patients with MPM, male and female patients were 34 and 29. CRSwas performed in 47 patients and complete cytoreduction(CC-0) was performed in 14(22%)patients. Mean numbers of resected peritoneal sectors and organs were 5.2(1-13), and 2.9(0- 9), respectively. Hyperthermic intraperitoneal chemoperfusion(HIPEC)was performed in 27 patients. Grade 1/2, Grade 3, and Grade 4 complications were experienced in 5, 6, and 3 patients, respectively. One patient died of sepsis, and the mortality rate was 2.3%. Independent prognostic factors for favorable prognosis were performance of HIPEC, peritoneal cancer index (PCI)score C12, no distant metastasis and histologic epithelial type. Relative risk of no HIPEC, PCI score B13, presence of distant metastasis and non epithelial type were 7.69, 22.1, 3.6 and 3.9, respectively. CONCLUSIONS: Risk factors for death after comprehensive treatment were no HIPEC, PCI score B13, and non epithelial type. However, only 11(17%)patients showed PCI score C12. Accordingly, PCI score should be reducedC12 before CRSby neoadjuvant chemotherapy.


Assuntos
Hipertermia Induzida , Mesotelioma , Neoplasias Peritoneais , Quimioterapia Adjuvante , Quimioterapia do Câncer por Perfusão Regional , Feminino , Humanos , Masculino , Mesotelioma/diagnóstico , Mesotelioma/terapia , Neoplasias Peritoneais/diagnóstico , Neoplasias Peritoneais/terapia , Prognóstico , Taxa de Sobrevida
15.
Clin Transl Oncol ; 21(10): 1336-1342, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30788836

RESUMO

INTRODUCTION: Neurological immune-related adverse events are a rare but potentially deadly complication after immune checkpoint inhibitor (ICI) treatment. As multiple sclerosis (MS) is an immune-mediated disease, it is unknown how ICI treatment may affect outcomes. METHODS: We analyzed the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database for pembrolizumab, atezolizumab, nivolumab, ipilimumab, avelumab, and durvalumab 2 years prior their FDA approval until December 31, 2017, to include all cases with confirmed diagnosis/relapse of MS. We also included cases reported in the literature and a patient from our institution. RESULTS: We identified 14 cases of MS with median age of presentation of 52 years. Indications for ICI included melanoma in 7 (36.36%) cases, non-small cell lung carcinoma in 2 (18.18%) cases, 1 case (9.09%) each of pleural mesothelioma, renal cell carcinoma, and colorectal cancer, and unreported in 2 (18.18%) cases. History of MS was confirmed in 8 (57.1%) cases. Median time to beginning of symptoms was 29 days with rapid disease progression; two patients died due to their relapse. Median time for symptom resolution was 8 weeks. Outcomes did not vary by comparing CTLA-4 and PD-1/PD-L1 inhibitors. CONCLUSIONS: Reported MS relapses after ICI are rare, but the adverse events described include rapid neurologic progression and death. Larger and prospective studies are warranted to assess disability and long-term outcomes and outweigh the risks of starting immunotherapy in patients with MS.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Imunoterapia/efeitos adversos , Esclerose Múltipla/complicações , Neoplasias/terapia , Adulto , Idoso , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Antígeno CTLA-4/antagonistas & inibidores , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma de Células Renais/terapia , Neoplasias Colorretais/terapia , Progressão da Doença , Feminino , Humanos , Imunoterapia/métodos , Ipilimumab/efeitos adversos , Neoplasias Renais/terapia , Neoplasias Pulmonares/terapia , Masculino , Melanoma/terapia , Mesotelioma/terapia , Pessoa de Meia-Idade , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/mortalidade , Neoplasias/complicações , Nivolumabe/efeitos adversos , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Recidiva , Estudos Retrospectivos , Resultado do Tratamento
16.
Genome Med ; 11(1): 8, 2019 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-30777124

RESUMO

BACKGROUND: Malignant peritoneal mesothelioma (PeM) is a rare and fatal cancer that originates from the peritoneal lining of the abdomen. Standard treatment of PeM is limited to cytoreductive surgery and/or chemotherapy, and no effective targeted therapies for PeM exist. Some immune checkpoint inhibitor studies of mesothelioma have found positivity to be associated with a worse prognosis. METHODS: To search for novel therapeutic targets for PeM, we performed a comprehensive integrative multi-omics analysis of the genome, transcriptome, and proteome of 19 treatment-naïve PeM, and in particular, we examined BAP1 mutation and copy number status and its relationship to immune checkpoint inhibitor activation. RESULTS: We found that PeM could be divided into tumors with an inflammatory tumor microenvironment and those without and that this distinction correlated with haploinsufficiency of BAP1. To further investigate the role of BAP1, we used our recently developed cancer driver gene prioritization algorithm, HIT'nDRIVE, and observed that PeM with BAP1 haploinsufficiency form a distinct molecular subtype characterized by distinct gene expression patterns of chromatin remodeling, DNA repair pathways, and immune checkpoint receptor activation. We demonstrate that this subtype is correlated with an inflammatory tumor microenvironment and thus is a candidate for immune checkpoint blockade therapies. CONCLUSIONS: Our findings reveal BAP1 to be a potential, easily trackable prognostic and predictive biomarker for PeM immunotherapy that refines PeM disease classification. BAP1 stratification may improve drug response rates in ongoing phases I and II clinical trials exploring the use of immune checkpoint blockade therapies in PeM in which BAP1 status is not considered. This integrated molecular characterization provides a comprehensive foundation for improved management of a subset of PeM patients.


Assuntos
Biomarcadores Tumorais/genética , Haploinsuficiência , Mesotelioma/genética , Neoplasias Peritoneais/genética , Proteínas Supressoras de Tumor/genética , Ubiquitina Tiolesterase/genética , Biomarcadores Tumorais/metabolismo , Humanos , Imunoterapia , Mesotelioma/classificação , Mesotelioma/terapia , Mutação , Neoplasias Peritoneais/classificação , Neoplasias Peritoneais/terapia , Microambiente Tumoral , Proteínas Supressoras de Tumor/metabolismo , Ubiquitina Tiolesterase/metabolismo
17.
Ann Diagn Pathol ; 39: 74-77, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30798074

RESUMO

Malignant Mesothelioma is an uncommon tumor that usually presents with diffuse pleural involvement and carries a dismal prognosis. Rarely, however, it can present as a localized, circumscribed mass or focal pleural lesion without evidence of diffuse spread. We found four such cases in our database. Three patients had localized epithelioid malignant mesothelioma and one had localized sarcomatoid mesothelioma. These localized tumors are a potential diagnostic pitfall for the pathologists as well as radiologists, especially those practicing in a community setting. Herein we discuss the clinicopathologic features of our cases along with a review of literature.


Assuntos
Terapia Combinada/métodos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Mesotelioma/patologia , Mesotelioma/terapia , Adulto , Idoso , Carboplatina/uso terapêutico , Cisplatino/uso terapêutico , Evolução Fatal , Feminino , Humanos , Masculino , Pemetrexede/uso terapêutico , Radioterapia , Procedimentos Cirúrgicos Torácicos
18.
Clin Respir J ; 13(5): 272-279, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30810270

RESUMO

OBJECTIVES: Malignant pleural mesothelioma and malignant pleural effusions are a major therapeutic challenge, and are associated with impairment in quality of life and increased mortality. Advances in systemic therapies of malignant pleural mesothelioma have demonstrated limited clinical benefit and there is ongoing interest in intrapleural immunotherapies which have been demonstrated to be well tolerated overall with variable clinical responses. We have reviewed the literature to provide a comprehensive summary of novel intrapleural immunotherapeutic paradigms, including oncolytic virus therapy, gene-mediated cytotoxic immunotherapy, direct cytokine-mediated immunotherapies, innate immunomodulators and adoptive transfer of intrapleural chimeric antigen receptor T-cell therapy. DATA SOURCES: A review of PubMed for original manuscripts and conference reports published between 1998 and 2018 pertaining to intrapleural immunotherapy, as well as examination of reference lists from reviewed manuscripts. STUDY SELECTION: Human clinical trials on intrapleural immunotherapies in subjects with malignant pleural mesothelioma or malignant pleural effusion were included in this review, including some relevant preclinical studies and anticipated ongoing trials reported on Clinicaltrials.gov. RESULTS: Twenty-six clinical trials were identified, in addition to three trials currently in progress. CONCLUSION: Intrapleural immunotherapies for pleural malignancy have demonstrated promise with regard to generating durable tumor-specific immune responses with possible clinical benefits which merit further investigation as part of multimodal chemotherapeutic and immunotherapeutic regimens.


Assuntos
Imunoterapia/métodos , Neoplasias Pulmonares/terapia , Mesotelioma/terapia , Neoplasias Pleurais/terapia , Humanos , Derrame Pleural Maligno/terapia , Qualidade de Vida
19.
Ann Surg Oncol ; 26(3): 852-860, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30635798

RESUMO

BACKGROUND: Well-differentiated papillary mesothelioma of the peritoneum (WDPMP) is a rare entity. Questions regarding management are still being debated as no more than 50 cases have been reported in the literature. OBJECTIVE: We aimed to analyze the clinical, therapeutic, and prognostic data of patients with WDPMP from the RENAPE observational registry. PATIENTS AND METHODS: All patients diagnosed with WDPMP and prospectively included in the RENAPE national registry between 2010 and 2018 were also included in our study. Expert pathologists from the RENA-PATH group confirmed all cases. All clinical, therapeutic, postoperative, and prognostic data were extracted and analyzed. RESULTS: We report on 56 patients with a mean age of 52 years (range 21-74). WDPMP was incidentally diagnosed during imaging or surgery in 16% and 36% of patients, respectively, and an association with synchronous malignancy was found in 18% of patients. Nine lesions showed discrete signs of fatty invasion. The median Peritoneal Cancer Index was 11 (range 0-33). Eleven patients were treated with definitive excision, 4 were treated with cytoreductive surgery (CRS) only, 37 were treated with CRS and hyperthermic intraperitoneal chemotherapy (HIPEC), and 2 were treated with CRS plus HIPEC plus early postoperative intraperitoneal chemotherapy. CRS was considered to be complete in 90% of cases. One patient died postoperatively and 16 patients (31%) faced postoperative complications. The median disease-free survival was 144 months; Four patients relapsed, with a median period of 27 months. No prognostic factors could be identified. CONCLUSIONS: Our analysis confirms the favorable prognosis of WDPMP. CRS and HIPEC could be a therapeutic option for diffuse, symptomatic, and/or recurrent disease.


Assuntos
Carcinoma Papilar/mortalidade , Quimioterapia do Câncer por Perfusão Regional/mortalidade , Procedimentos Cirúrgicos de Citorredução/mortalidade , Hipertermia Induzida/mortalidade , Mesotelioma/mortalidade , Neoplasias Peritoneais/mortalidade , Sistema de Registros/estatística & dados numéricos , Adulto , Idoso , Carcinoma Papilar/patologia , Carcinoma Papilar/terapia , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Mesotelioma/patologia , Mesotelioma/terapia , Pessoa de Meia-Idade , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/terapia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
20.
Carcinogenesis ; 40(4): 529-536, 2019 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-30649229

RESUMO

Malignant pleural mesothelioma (MPM) is a rare disease with a very poor prognosis. Previous studies have indicated that women experience longer survival compared with men. We analyzed 16 267 eligible patients (21.3% females) in the National Cancer Database to evaluate which clinical factors are independently predictive of longer survival. After adjusting for all covariates, survival was significantly better in females compared with males [HRadj: 0.81, 95% confidence interval (CI): 0.77-0.85]. Other factors significantly associated with better survival were younger age at diagnosis, higher income, lower comorbidity score, epithelial histology, earlier stage and receipt of surgical or medical treatment. After propensity matching, survival was significantly better for females compared with males [hazard ratio (HR): 0.86, 95% CI: 0.80-0.94]. After propensity matching within the epithelial group, survival remained significantly better for females compared with males (HR: 0.85, 95% CI: 0.74-0.97). This study adds information to the known significant gender survival difference in MPM by disentangling the effect of gender from the effect of age and histology, two known independent factors affecting survival. Circulating estrogen, present in young but not older women, and higher expression of the estrogen receptor beta in epithelial mesothelioma have been suggested to play a role in gender survival differences. These findings may lead to exploring new therapeutic options, such as targeting estrogen receptor beta, and considering hormonal therapy including estrogens for patients with otherwise limited prognosis.


Assuntos
Bases de Dados Factuais , Neoplasias Pulmonares/mortalidade , Mesotelioma/mortalidade , Neoplasias Pleurais/mortalidade , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Masculino , Mesotelioma/patologia , Mesotelioma/terapia , Pessoa de Meia-Idade , Neoplasias Pleurais/patologia , Neoplasias Pleurais/terapia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
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