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1.
Z Gastroenterol ; 58(2): 146-151, 2020 Feb.
Artículo en Alemán | MEDLINE | ID: mdl-32050285

RESUMEN

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.


Asunto(s)
Antineoplásicos/administración & dosificación , Procedimientos Quirúrgicos de Citorreducción , Hipertermia Inducida/métodos , Mesotelioma/terapia , Neoplasias Peritoneales/terapia , Protocolos de Quimioterapia Combinada Antineoplásica , Terapia Combinada , Procedimientos Quirúrgicos de Citorreducción/métodos , Femenino , Humanos , Masculino , Mesotelioma/tratamiento farmacológico , Mesotelioma/mortalidad , Mesotelioma/cirugía , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/mortalidad , Neoplasias Peritoneales/cirugía , Pronóstico , Tasa de Supervivencia
2.
Anticancer Res ; 39(11): 6241-6247, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31704853

RESUMEN

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.


Asunto(s)
Biomarcadores de Tumor/análisis , Neoplasias Pulmonares/enzimología , Mesotelioma/enzimología , Proteína Quinasa 1 Activada por Mitógenos/análisis , Neoplasias Pleurales/enzimología , Serina-Treonina Quinasas TOR/análisis , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/metabolismo , Cisplatino/administración & dosificación , Terapia Combinada/métodos , Femenino , Humanos , Inmunohistoquímica , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/terapia , Masculino , Mesotelioma/mortalidad , Mesotelioma/terapia , Persona de Mediana Edad , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Terapia Molecular Dirigida , Pemetrexed/administración & dosificación , Neoplasias Pleurales/mortalidad , Neoplasias Pleurales/terapia , Neumonectomía , Pronóstico , Proteínas Serina-Treonina Quinasas/análisis , Proteínas Serina-Treonina Quinasas/metabolismo , Serina-Treonina Quinasas TOR/metabolismo
3.
Anticancer Res ; 39(9): 5219-5223, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31519636

RESUMEN

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.


Asunto(s)
Proteínas Ligadas a GPI/metabolismo , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/mortalidad , Mesotelioma/complicaciones , Mesotelioma/mortalidad , Derrame Pleural Maligno/etiología , Derrame Pleural Maligno/metabolismo , Neoplasias Pleurales/complicaciones , Neoplasias Pleurales/mortalidad , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor , Femenino , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Masculino , Mesotelioma/diagnóstico , Mesotelioma/terapia , Persona de Mediana Edad , Derrame Pleural Maligno/diagnóstico , Derrame Pleural Maligno/terapia , Neoplasias Pleurales/diagnóstico , Neoplasias Pleurales/terapia , Pronóstico , Curva ROC , Resultado del Tratamiento
4.
Medicina (Kaunas) ; 55(8)2019 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-31366157

RESUMEN

Background and Objective: To present summary statistics regarding malignant mesothelioma (MM) mortality in Greece during the period 2005-2015 and compare it with previous decades, along with gender, age and geographical area analysis. Materials and Methods: The Hellenic Statistical Authority provided the data, which included all deaths for the period 1983 to 2015 that mentioned MM as the death cause in the corresponding death certificate. MM mortality rates have been calculated with respect to gender, age, and geographical location in Greece. Furthermore, a comparison analysis was made among three eleven consecutive year periods, in order to assess potential changes in the mortality rates. Results: The MM mortality rate has significantly increased during the period 2005-2015 both in males and females compared to earlier decades. The maximum number of MM deaths has shifted to an older age group of 70-80 years during the 2005-2015 period as compared to that of 1983-2004 in both genders. Additionally, MM mortality rates have significantly increased in all geographical areas except for the Epirus Prefecture. Conclusions: Our results demonstrate an increased MM mortality rate in Greece for the decade 2005-2015 as compared to the two previous decades. This increase is possibly due to the fact that the peak in asbestos production and use in Greece was in mid 1990s, while the asbestos ban came in effect in 2005. Based on these findings the MM epidemic in Greece has not yet peaked, therefore it is important to implement screening strategies for early MM detection.


Asunto(s)
Causas de Muerte/tendencias , Mesotelioma/mortalidad , Anciano , Anciano de 80 o más Años , Femenino , Mapeo Geográfico , Grecia/epidemiología , Humanos , Masculino , Mesotelioma/epidemiología , Persona de Mediana Edad , Enfermedades Profesionales/epidemiología , Enfermedades Profesionales/mortalidad
5.
J Surg Oncol ; 120(4): 794-802, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31309588

RESUMEN

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.


Asunto(s)
Neoplasias del Apéndice/mortalidad , Quimioterapia del Cáncer por Perfusión Regional/mortalidad , Neoplasias Colorrectales/mortalidad , Procedimientos Quirúrgicos de Citorreducción/mortalidad , Neoplasias Pulmonares/mortalidad , Mesotelioma/mortalidad , Neoplasias Ováricas/mortalidad , Neoplasias Peritoneales/mortalidad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Apéndice/patología , Neoplasias del Apéndice/terapia , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/terapia , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Inyecciones Intraperitoneales , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Masculino , Mesotelioma/patología , Mesotelioma/terapia , Persona de Mediana Edad , Neoplasias Ováricas/patología , Neoplasias Ováricas/terapia , Atención Perioperativa , Neoplasias Peritoneales/secundario , Neoplasias Peritoneales/terapia , Pronóstico , Estudios Prospectivos , Estudios Retrospectivos , Tasa de Supervivencia
6.
Adv Respir Med ; 87(2): 90-95, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31038719

RESUMEN

INTRODUCTION: Malignant pleural mesothelioma is a rare tumour with a bad prognosis. The only consensual prognostic factors are represented by the stage and the histologic type. Concerning the histologic type, epithelioid mesothelioma is known to have better prognosis in comparison with the sarcomatoid and biphasic types. Epithelioid mesotheliomas have been reported to be a heterogeneous prognostic group. Our aim was to assess the impact on the survival of different characteristics of epithelioid mesothelioma, including nuclear atypia, mitotic count, MIB-1 index, inflammatory host response, stromal desmoplasia, necrosis, vascular emboli and invasion depth. MATERIAL AND METHODS: We performed a study of survival of 30 malignant pleural mesotheliomas according to the different parameters studied. RESULTS: The study included 26 women and 4 men. The mean age of the patients was 61 years. The microscopic exam concluded to an epithelioid mesothelioma in 17 cases, sarcomatoid mesothelioma in 4 cases and biphasic mesothelioma in 9 cases. The 17 cases of epithelioid mesothelioma developed severe nuclear atypia in 6 cases and mild nuclear atypia in 11 cases. The mitotic count and the MIB-1 score were respectively inferior to 5 mitoses/50 HPF and inferior to 10% in 11 cases and were superior to 5 mitoses/50 HPF and superior to 10% in 6 cases. No vascular emboli were recorded. Tumour necrosis was reported in 1 case. The inflammatory host response was severe in 4 cases and mild in 13 cases. The tumoral stroma was desmoplastic in 4 cases. The invasion depth was superior to 0.5mm in 16 cases. The median overall survival amounted to 180 days. Nuclear atypia was the only feature that had impact on survival in the group of epithelioid mesothelioma. CONCLUSION: Our results highlight the correlation of nuclear atypia with survival.


Asunto(s)
Células Epitelioides/patología , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Mesotelioma/mortalidad , Mesotelioma/patología , Femenino , Humanos , Persona de Mediana Edad , Clasificación del Tumor , Pronóstico , Tasa de Supervivencia
7.
Oncol Res Treat ; 42(6): 334-341, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31063993

RESUMEN

BACKGROUND/AIMS: To investigate differences in blood routine indexes and the expression of cyclooxygenase-2 (COX-2) and nuclear factor-kappa B (NF-κB) in malignant peritoneal mesothelioma (MPeM) and their relationship with clinical prognosis. METHODS: We investigated changes in blood routine indexes between the MPeM patients and healthy subjects and detected the expression of COX-2 and NF-κB in peritoneal tissues by a streptavidin-peroxidase immunohistochemistry method. Potential prognostic factors were analyzed including age, gender, white blood cell count (WBC), absolute neutrophil count (ANC), absolute lymphocyte count (ALC), absolute platelet count (APC), absolute monocyte count (AMC), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), COX-2, and NF-κB. Cox regression model analysis established independent factors for the survival prognosis of the patients. RESULTS: Compared with the control group, AMC, MXD%, ANC, neutrophilic granulocyte percentage (NEUT%), APC, NLR, MLR, and PLR were markedly increased (p < 0.05) in the MPeM group. The positivity rates for COX-2 and NF-κB expression were 59.4 and 44.9%, respectively. Single factor analyses indicated that PLR, NLR, MLR, COX-2, and NF-κB were factors that affected the overall survival of MPeM patients, but multivariate analyses identified MLR and COX-2 as independent prognostic factors. CONCLUSIONS: High blood levels of MLR and COX-2 are adverse prognostic factors for patients with MPeM.


Asunto(s)
Ciclooxigenasa 2/sangre , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/diagnóstico , Mesotelioma/sangre , Mesotelioma/diagnóstico , FN-kappa B/sangre , Neoplasias Peritoneales/sangre , Neoplasias Peritoneales/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Plaquetas , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Recuento de Leucocitos , Neoplasias Pulmonares/mortalidad , Recuento de Linfocitos , Linfocitos/patología , Masculino , Mesotelioma/mortalidad , Persona de Mediana Edad , Monocitos/patología , Neutrófilos , Neoplasias Peritoneales/mortalidad , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Tasa de Supervivencia
8.
Cancer Epidemiol ; 60: 162-167, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-31030080

RESUMEN

BACKGROUND: This study is part of a national plan of epidemiological surveillance of malignant mesothelioma (MM) mortality in Italy. The paper shows the results of malignant peritoneal mesothelioma (MPeM) mortality study in Italian Regions and municipalities. METHODS: National Bureau of Statistics data for MPeM municipal mortality (ICD-10, Code C45.1) were analyzed in the time-window 2003-2014: mortality standardized rates (reference Italian population, census 2011), temporal trends of the annual national rates, Standardized Mortality Ratios and a municipal clustering analysis were performed. RESULTS: 747 deaths for MPeM were recorded (0.10/100,000): 464 in men (0.14/100,000) and in 283 women (0.07/100,000). No significant MPeM mortality temporal trend was found. Seventeen municipalities showed excesses of mortality for MPeM in at least one gender and/or overall population. Four clusters in male population, and one in women were identified. CONCLUSIONS: The study identifies some areas where remediation activities and/or health care actions may be warranted.


Asunto(s)
Asbestos/efectos adversos , Neoplasias Pulmonares/epidemiología , Mesotelioma/epidemiología , Neoplasias Peritoneales/epidemiología , Adulto , Anciano , Femenino , Humanos , Italia , Neoplasias Pulmonares/mortalidad , Masculino , Mesotelioma/mortalidad , Persona de Mediana Edad , Neoplasias Peritoneales/mortalidad , Análisis Espacial
9.
Ann Thorac Surg ; 108(3): 889-896, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31004585

RESUMEN

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.


Asunto(s)
Causas de Muerte , Disparidades en Atención de Salud , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/terapia , Mesotelioma/mortalidad , Mesotelioma/terapia , Neoplasias Pleurales/mortalidad , Neoplasias Pleurales/terapia , Adulto , Anciano , California , Estudios de Cohortes , Terapia Combinada , Bases de Datos Factuales , Supervivencia sin Enfermedad , Femenino , Adhesión a Directriz , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/diagnóstico , Masculino , Mesotelioma/diagnóstico , Persona de Mediana Edad , Neoplasias Pleurales/diagnóstico , Neumonectomía/métodos , Guías de Práctica Clínica como Asunto , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Medición de Riesgo , Análisis de Supervivencia
10.
J BUON ; 24(1): 391-396, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30941996

RESUMEN

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.


Asunto(s)
Mesotelioma/terapia , Neoplasias Peritoneales/terapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Terapia Combinada , Procedimientos Quirúrgicos de Citorreducción/métodos , Femenino , Humanos , Hipertermia Inducida/métodos , Cuidados Intraoperatorios/métodos , Masculino , Mesotelioma/mortalidad , Mesotelioma/patología , Persona de Mediana Edad , Neoplasias Peritoneales/mortalidad , Neoplasias Peritoneales/patología , Estudios Retrospectivos , Análisis de Supervivencia , Adulto Joven
11.
Ann Ist Super Sanita ; 55(1): 80-89, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30968842

RESUMEN

Here are reviewed the studies conducted on asbestos-amosite pollution and its effects on the health of workers exposed from 1928 to 1973 at the Collotta-Cis factory of Ledro, Italy. The methods adopted to conduct the initial research, involving the population itself and the local administrations are described. The data summarized include: epidemiological studies of mortality carried out in 1977-85 and updated in 2009; results of the investigations carried out throughout the 1980s on the health consequences on workers, their families and residents near the factory; process of environmental cleanup from asbestos of the industrial area, completed in 1989, and the pollution risk assessment in the whole Ledro Valley. Although this was a small community of about 400 workers, these studies show that exposure to asbestos is responsible for the death of 81 people (22 mesotheliomas, 21 asbestosis, 38 malignant tumors of the lung, digestive system, ovary), for 1400 years of life lost, and for about 100 invalidity pensions, as recognized to former workers by INAIL.


Asunto(s)
Asbesto Amosita/efectos adversos , Asbestosis/epidemiología , Restauración y Remediación Ambiental/métodos , Neoplasias/epidemiología , Adolescente , Adulto , Anciano , Asbestos , Asbestosis/mortalidad , Niño , Brotes de Enfermedades , Femenino , Humanos , Italia/epidemiología , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/etiología , Neoplasias Pulmonares/mortalidad , Masculino , Mesotelioma/epidemiología , Mesotelioma/etiología , Mesotelioma/mortalidad , Persona de Mediana Edad , Neoplasias/inducido químicamente , Neoplasias/mortalidad , Exposición Profesional/estadística & datos numéricos , Adulto Joven
12.
BMJ Case Rep ; 12(3)2019 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-30936339

RESUMEN

India is the largest consumer of asbestos in the world. There is no report from India of mesothelioma related to asbestos. The case is a 42-year-old man who died of pleural mesothelioma. He was exposed to asbestos domestically and from the environment since birth. Two of his close family members worked in a factory that used asbestos. The living quarter of the family was within the premises of the factory. Asbestos waste was strewn on the grounds surrounding the quarters. After decades of legal battles by workers and families exposed to asbestos, Indian courts have ordered remedial measures and compensation to people, who are exposed to asbestos at work and the environment. Mesothelioma, currently in epidemic proportions in the west where asbestos production was banned in the 1990s, could rise to alarming levels in the next decades in India if the legal remedial measures are not implemented soon.


Asunto(s)
Contaminantes Ocupacionales del Aire/efectos adversos , Asbestos/efectos adversos , Exposición a Riesgos Ambientales/efectos adversos , Neoplasias Pulmonares/diagnóstico , Mesotelioma/diagnóstico , Exposición Profesional/efectos adversos , Neoplasias Pleurales/diagnóstico , Adulto , Compensación y Reparación/legislación & jurisprudencia , Exposición a Riesgos Ambientales/legislación & jurisprudencia , Resultado Fatal , Humanos , India , Neoplasias Pulmonares/inducido químicamente , Neoplasias Pulmonares/mortalidad , Masculino , Mesotelioma/inducido químicamente , Mesotelioma/mortalidad , Exposición Profesional/legislación & jurisprudencia , Neoplasias Pleurales/inducido químicamente , Neoplasias Pleurales/mortalidad , Indemnización para Trabajadores/legislación & jurisprudencia
13.
Mol Biol Rep ; 46(3): 2713-2720, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30840203

RESUMEN

Malignant pleural mesothelioma (MPM) is a rare and aggressive form of tumour. Some mesotheliomas have been proven to be highly immunogenic. Here, we investigated the correlation between tumour infiltrating lymphocytes (TILs) or programmed cell death ligand 1 (PD-L1) expression with overall survival (OS) in patients with MPM. 62 Paraffin-embedded formalin fixed (PEFF) samples were analysed for TILs and PD-L1 expression. Patients were divided in 4 groups according to a cut-off of the percentage of TILs found per sample as measured by immunohistichemistry: "0" or absent (between 0 and 5%), "1" or low (between 6 and 25%), "2" or moderate (between 26 and 50%) and "3" or high (between 51 and 75%). OS was then correlated with different TILs' expression patterns. Moreover, PD-L1 expression was assessed within the tumour as well as in the adjacent stroma on the same samples. Higher expression of peritumoral TILs (Group 2 + 3) versus Group 0 and 1 correlated with improved OS (p-value = 0.02). On the contrary PD-L1 expression seemed to be inversely correlated with clinical outcomes, even in the absence of statistical significance (HR 1.76; p = 0.083 95% IC 0.92-3.36 in areas within the tumour; HR 1.60; p = 0.176 95%; IC 0.80-3.19 in areas within the stroma). No relationship between TILs and PD-L1 expression was identified. Our research supports the use of TILs and PD-L1 expression as potential outcome predictors in patients with MPM. The use of TILs and PD-L1 as biomarkers for checkpoint inhibitors' efficacy warrants future investigation.


Asunto(s)
Antígeno B7-H1/metabolismo , Neoplasias Pulmonares/genética , Linfocitos Infiltrantes de Tumor/metabolismo , Mesotelioma/genética , Adulto , Anciano , Anciano de 80 o más Años , Antígeno B7-H1/fisiología , Biomarcadores de Tumor/metabolismo , Femenino , Humanos , Inmunohistoquímica/métodos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidad , Linfocitos Infiltrantes de Tumor/fisiología , Masculino , Mesotelioma/metabolismo , Mesotelioma/mortalidad , Persona de Mediana Edad , Neoplasias Pleurales/genética , Pronóstico , Estudios Retrospectivos , Transcriptoma/genética , Resultado del Tratamiento
14.
Br J Cancer ; 120(4): 387-397, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30739911

RESUMEN

BACKGROUND: The Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS/NCT00651456) phase 3 trial demonstrated the superiority of bevacizumab plus pemetrexed-cisplatin triplet over chemotherapy alone in 448 malignant pleural mesothelioma (MPM) patients. Here, we evaluated the prognostic role of Hippo pathway gene promoter methylation. METHODS: Promoter methylations were assayed using methylation-specific polymerase chain reaction in samples from 223 MAPS patients, evaluating their prognostic value for overall survival (OS) and disease-free survival in univariate and multivariate analyses. MST1 inactivation effects on invasion, soft agar growth, apoptosis, proliferation, and YAP/TAZ activation were investigated in human mesothelial cell lines. RESULTS: STK4 (MST1) gene promoter methylation was detected in 19/223 patients tested (8.5%), predicting poorer OS in univariate and multivariate analyses (adjusted HR: 1.78, 95% CI (1.09-2.93), p = 0.022). Internal validation by bootstrap resampling supported this prognostic impact. MST1 inactivation reduced cellular basal apoptotic activity while increasing proliferation, invasion, and soft agar or in suspension growth, resulting in nuclear YAP accumulation, yet TAZ cytoplasmic retention in mesothelial cell lines. YAP silencing decreased invasion of MST1-depleted mesothelial cell lines. CONCLUSIONS: MST1/hippo kinase expression loss is predictive of poor prognosis in MPM patients, leading to nuclear YAP accumulation and electing YAP as a putative target for therapeutic intervention in human MPM.


Asunto(s)
Metilación de ADN , Factor de Crecimiento de Hepatocito/genética , Neoplasias Pulmonares/genética , Mesotelioma/genética , Neoplasias Pleurales/genética , Regiones Promotoras Genéticas , Proteínas Serina-Treonina Quinasas/genética , Proteínas Proto-Oncogénicas/genética , Apoptosis , Proteínas de Ciclo Celular , Línea Celular Tumoral , Proliferación Celular , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Mesotelioma/tratamiento farmacológico , Mesotelioma/mortalidad , Mesotelioma/patología , Invasividad Neoplásica , Proteínas Nucleares/metabolismo , Neoplasias Pleurales/tratamiento farmacológico , Neoplasias Pleurales/mortalidad , Neoplasias Pleurales/patología , Factores de Transcripción/metabolismo
15.
Cancer Epidemiol ; 59: 75-82, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30708341

RESUMEN

BACKGROUND: Historically pleural infection was thought to be associated with longer survival in thoracic malignancies. The aim of this population-based cohort study was to investigate this hypothesis in mesothelioma, using national data from a high incidence country. METHODS: Case records for all patients with mesothelioma seen in English hospitals between 01/01/2005 and 31/12/2014 were extracted from Hospital Episode Statistics using International Classification of Diseases Tenth Edition (ICD-10) codes. Episodes of pleural infection were identified. Linked mortality data was obtained from the Office of National Statistics. The primary outcome was all-cause mortality. The explanatory variable was pleural infection. Cox proportional hazards model was used to analyse survival, with pleural infection, chemotherapy and thoracic surgery handled as time-variable co-factors. RESULTS: Of 22,215 patients with mesothelioma, 512 (2.3%) developed pleural infection at some point in their illness. Overall median survival was 7.0 months (IQR 2.3-16.4). Pleural infection was associated with shorter survival in the immediate post-infection period (up to 30 days - HR 1.81, 95% CI 1.45-2.22) and longer term (>30 days - HR 1.81, 95% CI 1.63-1.99). Other factors associated with increased mortality were age, male gender and being diagnosed as an inpatient. Receiving chemotherapy and being less economically deprived were associated with longer survival. CONCLUSION: Pleural infection occurred in 2.3% of people with mesothelioma and was associated with shorter survival. This refutes previous reports suggesting pleural infection may be associated with better outcomes in thoracic malignancy.


Asunto(s)
/complicaciones , Mesotelioma/mortalidad , Pleura , Neoplasias Pleurales/mortalidad , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Inglaterra/epidemiología , Femenino , Humanos , Masculino , Mesotelioma/complicaciones , Persona de Mediana Edad , Neoplasias Pleurales/complicaciones , Modelos de Riesgos Proporcionales
16.
Anticancer Res ; 39(2): 839-845, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30711965

RESUMEN

BACKGROUND: Malignant peritoneal mesothelioma (MPeM) is a rare type of cancer with a poor prognosis. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) have been shown to improve survival. Treatment and survival of patients with MPeM have not been previously studied in Finland. MATERIALS AND METHODS: The data consisted of all patients diagnosed with MPeM during years 2000-2012 in Finland, including cancer notifications, death certificates and information about asbestos exposure. RESULTS: Among 50/94 (53.2%) patients treated for MPeM, 44/50 (88.0%) were treated palliatively, 4/50 (8.0%) with radical surgery and chemotherapy, and 2/50 (4.0%) with CRS plus HIPEC. Five-year survival was 50.0% for those treated with CRS plus HIPEC and 75.0% for those treated with radical surgery and chemotherapy. Radical surgery with chemotherapy was associated with significantly longer survival compared to radiation (p=0.008), chemotherapy and radiation (p=0.043), surgery, chemotherapy and radiation (p=0.039), and palliative surgery (p=0.009). CONCLUSION: Treatment of MPeM is heterogenic in Finland. CRS plus HIPEC, and radical surgery with chemotherapy seem to increase the survival. Patients considered candidates for radical surgery should be sent to specialized centers for further assessment.


Asunto(s)
Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/cirugía , Mesotelioma/tratamiento farmacológico , Mesotelioma/cirugía , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Asbestos/efectos adversos , Procedimientos Quirúrgicos de Citorreducción/mortalidad , Femenino , Finlandia , Humanos , Hipertermia Inducida , Neoplasias Pulmonares/mortalidad , Masculino , Mesotelioma/mortalidad , Persona de Mediana Edad , Neoplasias Peritoneales/mortalidad , Pronóstico , Estudios Retrospectivos , Resultado del Tratamiento
17.
Hum Pathol ; 87: 11-17, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30794891

RESUMEN

Malignant mesothelioma (MM) is an aggressive neoplasm with poor prognosis. The Dako PD-L1 22C3 and 28-8 pharmDx assays are approved by the US Food and Drug Administration (FDA) as companion and complementary diagnostics for the anti-PD-1 drugs pembrolizumab and nivolumab, respectively. Data from multiple clinical trials indicate that immunotherapy has antitumor activity in advanced malignant pleural (MPM) and peritoneal mesothelioma (MPeM). However, large studies of PD-L1 expression in MM using the FDA-approved anti-PD-L1 assays are lacking. We stained tissue microarray sections (N = 125; 112 MPM and 13 MPeM) using 2 FDA-approved clinical immunohistochemical makers for PD-L1 expression: Dako PD-L1 22C3 pharmDx and Dako PD-L1 28-8 pharmDx. Overall, 22% (27/125) of MMs were positive using the 22C3 assay, whereas 27% (32/117) were positive using the 28-8 assay, using a tumor proportion score cutoff of 1%. Tumor cell PD-L1 expression was strongly correlated with PD-L1 expression on tumor-associated immune cells. No significant difference in PD-L1 expression was observed by patient sex, age, treatment history, pathologic stage, or histologic subtype. However, the proportion of cases positive for PD-L1 expression was higher among MPeM compared to MPM (P = .007 for 22C3 assay; P = .04 for 28-8 assay). PD-L1 is expressed in a substantial proportion of MM cases, as measured by FDA-approved companion assays for widely used immunotherapeutic drugs. PD-L1 expression is particularly prevalent in MPeM. These findings support large clinical studies to further examine PD-L1 as a biomarker for a subset of MM patients that may benefit from immunotherapy.


Asunto(s)
Antígeno B7-H1/metabolismo , Neoplasias Pulmonares/metabolismo , Mesotelioma/metabolismo , Neoplasias Peritoneales/metabolismo , Neoplasias Pleurales/metabolismo , Anciano , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Biomarcadores de Tumor/metabolismo , Femenino , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Mesotelioma/tratamiento farmacológico , Mesotelioma/mortalidad , Mesotelioma/patología , Persona de Mediana Edad , Nivolumab/uso terapéutico , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/mortalidad , Neoplasias Peritoneales/patología , Neoplasias Pleurales/tratamiento farmacológico , Neoplasias Pleurales/mortalidad , Neoplasias Pleurales/patología , Pronóstico , Tasa de Supervivencia , Resultado del Tratamiento
18.
Am J Surg ; 217(5): 923-927, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30760409

RESUMEN

BACKGROUND: Cytoreductive surgery and heated intraperitoneal chemotherapy (CRS/HIPEC) are commonly used in the treatment of peritoneal carcinomatosis (PC) originating from colorectal, appendiceal and ovarian cancers. It is unclear what benefit CRS/HIPEC might have for PC from uncommon etiologies, therefore we sought to describe local practice patterns and evaluate overall survival (OS). METHODS: All patients who had CRS/HIPEC between 2000 and 2016 were identified using our institutional cancer database. Patients with appendiceal, colorectal, and ovarian pathologies were excluded. Kaplan-Meier curves were used to estimate and demonstrate 5-year OS. Cox regression analysis was performed to determine factors associated with OS. RESULTS: Of all patients treated with CRS/HIPEC at our institution, 38 were treated for PC of rare origin. Etiologies included 23 patients with mesothelioma, 8 with primary peritoneal carcinoma, 4 with small bowel tumours and 3 with gastric cancer. Median OS of 35.4, 20.8, 25.4, and 20.2 months were obtained for each group respectively. 5-year OS for each pathology was 8.7%, 0.0%, 25.0%, and 33.3% respectively with corresponding mean PCI of 31.3, 23.6, 21.5, and 12.7. No independent prognostic factors were significant on Cox regression analysis. Median length of stay was 19 days. Readmission rate within 30 days of discharge was 7.9%. Rate of Grade III/IV complications was 34.2%. No thirty-day mortality. CONCLUSION: Survivals beyond 20 months can be obtained with the use of CRS/HIPEC for rare PC etiologies aligning with results of other groups. CRS/HIPEC in well-selected patients demonstrates a clinical benefit and this could be confirmed with a multi-institutional study.


Asunto(s)
Quimioterapia del Cáncer por Perfusión Regional , Procedimientos Quirúrgicos de Citorreducción , Neoplasias Peritoneales/secundario , Neoplasias Peritoneales/terapia , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Humanos , Neoplasias Intestinales/mortalidad , Neoplasias Intestinales/patología , Intestino Delgado/patología , Tiempo de Internación/estadística & datos numéricos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Mesotelioma/mortalidad , Mesotelioma/patología , Persona de Mediana Edad , Readmisión del Paciente/estadística & datos numéricos , Neoplasias Peritoneales/mortalidad , Estudios Retrospectivos , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Adulto Joven
19.
Ann Surg Oncol ; 26(3): 852-860, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30635798

RESUMEN

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.


Asunto(s)
Carcinoma Papilar/mortalidad , Quimioterapia del Cáncer por Perfusión Regional/mortalidad , Procedimientos Quirúrgicos de Citorreducción/mortalidad , Hipertermia Inducida/mortalidad , Mesotelioma/mortalidad , Neoplasias Peritoneales/mortalidad , Sistema de Registros/estadística & datos numéricos , Adulto , Anciano , Carcinoma Papilar/patología , Carcinoma Papilar/terapia , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Masculino , Mesotelioma/patología , Mesotelioma/terapia , Persona de Mediana Edad , Neoplasias Peritoneales/patología , Neoplasias Peritoneales/terapia , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Adulto Joven
20.
Carcinogenesis ; 40(4): 529-536, 2019 06 10.
Artículo en Inglés | MEDLINE | ID: mdl-30649229

RESUMEN

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.


Asunto(s)
Bases de Datos Factuales , Neoplasias Pulmonares/mortalidad , Mesotelioma/mortalidad , Neoplasias Pleurales/mortalidad , Anciano , Anciano de 80 o más Años , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Masculino , Mesotelioma/patología , Mesotelioma/terapia , Persona de Mediana Edad , Neoplasias Pleurales/patología , Neoplasias Pleurales/terapia , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia
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