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2.
Nat Med ; 25(10): 1519-1525, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31591589

RESUMO

Malignant mesothelioma (MM) is an aggressive cancer primarily diagnosed on the basis of histological criteria1. The 2015 World Health Organization classification subdivides mesothelioma tumors into three histological types: epithelioid, biphasic and sarcomatoid MM. MM is a highly complex and heterogeneous disease, rendering its diagnosis and histological typing difficult and leading to suboptimal patient care and decisions regarding treatment modalities2. Here we have developed a new approach-based on deep convolutional neural networks-called MesoNet to accurately predict the overall survival of mesothelioma patients from whole-slide digitized images, without any pathologist-provided locally annotated regions. We validated MesoNet on both an internal validation cohort from the French MESOBANK and an independent cohort from The Cancer Genome Atlas (TCGA). We also demonstrated that the model was more accurate in predicting patient survival than using current pathology practices. Furthermore, unlike classical black-box deep learning methods, MesoNet identified regions contributing to patient outcome prediction. Strikingly, we found that these regions are mainly located in the stroma and are histological features associated with inflammation, cellular diversity and vacuolization. These findings suggest that deep learning models can identify new features predictive of patient survival and potentially lead to new biomarker discoveries.


Assuntos
Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Mesotelioma/diagnóstico , Mesotelioma/patologia , Prognóstico , Aprendizado Profundo , Feminino , Humanos , Neoplasias Pulmonares/classificação , Masculino , Mesotelioma/classificação , Gradação de Tumores
3.
BMC Res Notes ; 12(1): 636, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31564247

RESUMO

OBJECTIVE: Asbestos was widely used in construction in both a friable and a compact form until the 1990s, before its use was banned. Today, many of these materials are still in situ and represent a source of risk for construction workers. The objective of the study was to analyse the cases of mesothelioma arising among construction workers registered in the Apulia regional register of mesothelioma. RESULTS: For the period 1993-2018, there were 178 male cases, and 10.2% of the cases were present in the regional register. The average age at diagnosis was 64.7 years. The site was pleural in 96.06% of cases, with a diagnosis of certainty in 86.5% of the total cases and 61.8% of cases with epithelial histology. The average latency is 43.9 years. In 75.2% of cases, the exposure began between 1941 and 1970, with an average duration of 24.3 years. The age at the start of exposure in 68.5% of cases is between 8 and 20 years. The ORs were 2.5 (C.I. 95% 1.01-6.17) for the epithelioid histotype and the high duration of exposure. The data underline the need for prevention and information on all activities involving construction workers in which asbestos-containing materials are still used.


Assuntos
Asbestos/efeitos adversos , Exposição Ambiental/efeitos adversos , Neoplasias Pulmonares/epidemiologia , Mesotelioma/epidemiologia , Exposição Ocupacional/efeitos adversos , Sistema de Registros , Adulto , Idoso , Idoso de 80 Anos ou mais , Indústria da Construção/instrumentação , Humanos , Incidência , Itália/epidemiologia , Pulmão/efeitos dos fármacos , Pulmão/patologia , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Masculino , Mesotelioma/induzido quimicamente , Mesotelioma/diagnóstico , Mesotelioma/patologia , Pessoa de Meia-Idade
4.
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.
BMJ Case Rep ; 12(8)2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31420427

RESUMO

Acute abdominal pain is a common symptom in young women. We describe a patient with acute illness and severe lower abdominal pain. Laboratory tests were normal except for mildly deranged inflammatory markers. No abnormalities were reported on abdominal ultrasonography and MRI, whereas diagnostic laparoscopy revealed a tumour located dorsally from the uterus. We resected the tumour and pathology results showed a well-differentiated papillary mesothelioma of the peritoneum (WDPMP). Microscopy showed evidence of acute ischaemia in the resected lesion, which was likely the cause of the acute abdominal pain. WDPMP is a rare disease that arises from the serous membranes which does not seem to have a relation to asbestos exposure. Generally, WDPMP has a mild clinical course and good long-term prognosis.


Assuntos
Dor Abdominal/diagnóstico , Dor Aguda/diagnóstico , Mesotelioma/diagnóstico , Neoplasias Peritoneais/diagnóstico , Dor Abdominal/etiologia , Dor Aguda/etiologia , Adulto , Feminino , Humanos , Mesotelioma/complicações , Neoplasias Peritoneais/complicações
7.
Laeknabladid ; 105(7): 327-334, 2019.
Artigo em Islandês | MEDLINE | ID: mdl-31411568

RESUMO

Asbestos are crystallized silicate minerals that form fibers with different structures and characteristics. Asbestos fibers are very durable and can tolerate very high temperatures. Therefore it was common to use asbestos as a fire retardants, heat insulation and where high temperature is used. Asbestos has been banned in Iceland from 1983 but can still be found in large amounts in buildings, ships and hot water pipes. Large amounts of asbestos were imported in the years before the ban but diminished soon to almost nothing today. Needle or filamentous shaped dust is released when working with asbestos. It is this dust that is dangerous for health. The latent time from exposure to disease can be up to forty years. Asbestos reaches the lungs via inhalation and can cause asbestosis that is a form of lung fibrosis with slow progression. Asbestos can also cause benign pleural effusions, pleural plaques and diffuse pleural thickening. Asbestos is a carcinogen. Lung cancer is most common but asbestos is also a risk factor for cancers of other organs. Mesothelioma is most common in the pleura but can be seen in other membranes. The incidence of these tumors is high in Iceland and is still increasing among males. Of all the European countries mortality is highest in Iceland. It is important for physicians to include asbestos exposure in the differential diagnosis of lung diseases and when lung cancer is diagnosed.


Assuntos
Asbestos/efeitos adversos , Asbestose/epidemiologia , Materiais de Construção/efeitos adversos , Exposição Ambiental/efeitos adversos , Neoplasias Pulmonares/epidemiologia , Mesotelioma/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Asbestose/diagnóstico por imagem , Asbestose/patologia , Feminino , Humanos , Islândia/epidemiologia , Incidência , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Masculino , Mesotelioma/diagnóstico , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Distribuição por Sexo , Fatores de Tempo
8.
J Pak Med Assoc ; 69(8): 1103-1107, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31431761

RESUMO

OBJECTIVE: To assess the diagnostic value of video-assisted thoracoscopic surgery in exudative pleural effusions, and to evaluated the frequency of malignancy development with long term follow-up of patients defined as nonspecific pleuritis after surgery. . METHODS: The retrospective study was conducted at Yedikule Chest Diseases and Thoracic Surgery Training and Research Hospital, Istanbul, Turkey, and comprised data of patients with undiagnosed exudative pleural effusions seen between January 2008 and December 2013. Data related to clinical, radiological, thoracoscopical, histopathological and follow-up periods were obtained from the hospital records. SPSS 15 was used for data analysis. RESULTS: Of the 229 patients, 145(63.3%) were males and 84(36.7%) were females. The overall mean age was 54.5 }15.1 years. Malignancy was found in 84 (36.6%) patients, and tuberculosis in 26(11.4%). The remaining 119(52%) patients had nonspecific pleuritis and their mean follow-up period was 29.2}27.1 months (range: 1-103 months). Video-assisted thoracoscopic surgery was repeated in 3(2.52%) patients in the 1st, 4th and 16th months of followup period due to the recurrence of pleural effusion. Tuberculosis and mesothelioma were diagnosed in 1(0.8%) and 2(1.7%) cases, respectively. CONCLUSIONS: Video-assisted thoracoscopic surgery was found to be a valuable diagnostic procedure in patients with undiagnosed exudative pleural effusion.


Assuntos
Neoplasias Pulmonares/diagnóstico , Linfoma/diagnóstico , Mesotelioma/diagnóstico , Derrame Pleural/etiologia , Neoplasias Pleurais/diagnóstico , Pleurisia/diagnóstico , Tuberculose Pleural/diagnóstico , Adulto , Idoso , Biópsia , Exsudatos e Transudatos , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/patologia , Linfoma/complicações , Linfoma/patologia , Masculino , Mesotelioma/complicações , Mesotelioma/patologia , Pessoa de Meia-Idade , Neoplasias Pleurais/complicações , Neoplasias Pleurais/patologia , Neoplasias Pleurais/secundário , Pleurisia/complicações , Pleurisia/patologia , Estudos Retrospectivos , Toracentese , Cirurgia Torácica Vídeoassistida , Tuberculose Pleural/complicações , Tuberculose Pleural/patologia , Turquia
9.
Pathologe ; 40(4): 393-411, 2019 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-31243551

RESUMO

Epithelioid soft tissue tumors consist exclusively of epithelioid tumor cells. Biphasic tumors are composed of both a spindle-cell and an epithelioid component. The rare mixed tumors of soft tissue show a broader variety of cellular and stromal differentiation but also include at least one, possibly several, epithelioid portions.The close morphological similarity of some of these entities with each other, as well as with the more frequent soft tissue metastases of carcinomas, carcinosarcomas, and melanomas, to malignant mesothelioma and certain lymphomas, can often make the correct diagnosis extremely difficult. Recent advances in the detection of certain molecular alterations (mostly chromosomal translocations) have contributed to changes in tumor classification but also to improved pathological diagnostics (e.g. through the development of potent diagnostic antibodies) and biological understanding.The present overview should help the pathologist in the diagnosis of these rare tumors through the classical approach of morphological pattern recognition. The most important entities are discussed and illustrated in more detail, with the incorporation of the latest immunohistochemical and molecular aspects and the differential diagnosis of similar tumors.


Assuntos
Mesotelioma , Sarcoma , Neoplasias de Tecidos Moles , Biomarcadores Tumorais , Diagnóstico Diferencial , Humanos , Imuno-Histoquímica , Mesotelioma/diagnóstico , Mesotelioma/patologia , Sarcoma/patologia , Neoplasias de Tecidos Moles/diagnóstico , Neoplasias de Tecidos Moles/patologia
10.
Pathol Res Pract ; 215(7): 152462, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31146976

RESUMO

Signet ring cell mesothelioma is a rare variant of epithelioid mesothelioma with limited cases published. It has a male predilection and most commonly occurs on pleura; it can also arise in the peritoneal cavity. The signet ring cell morphology can pose a challenge leading to a potential diagnostic error. A variety of benign and malignant diseases, including reactive histiocytic hyperplasia, adenocarcinoma, melanoma, and lymphoma with signet ring cell morphology should be considered in the differential diagnosis. In signet ring cell mesothelioma work up, mucin stains are of limited value. Even though immunohistochemistry is routinely used in mesothelioma diagnosis, there is no sole specific mesothelial marker. Hence, a panel of mesothelial and epithelial markers are used; these should be interpreted with caution especially in this variant. Electron microscopy and genetic testing can be very helpful in distinguishing signet ring cell mesothelioma from its mimickers.


Assuntos
Carcinoma de Células em Anel de Sinete/diagnóstico , Mesotelioma/diagnóstico , Biomarcadores Tumorais/metabolismo , Carcinoma de Células em Anel de Sinete/metabolismo , Carcinoma de Células em Anel de Sinete/patologia , Diagnóstico Diferencial , Humanos , Mesotelioma/metabolismo , Mesotelioma/patologia
11.
Oncol Res Treat ; 42(6): 334-341, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31063993

RESUMO

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.


Assuntos
Ciclo-Oxigenase 2/sangue , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/diagnóstico , Mesotelioma/sangue , Mesotelioma/diagnóstico , NF-kappa B/sangue , Neoplasias Peritoneais/sangue , Neoplasias Peritoneais/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Plaquetas , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Contagem de Leucócitos , Neoplasias Pulmonares/mortalidade , Contagem de Linfócitos , Linfócitos/patologia , Masculino , Mesotelioma/mortalidade , Pessoa de Meia-Idade , Monócitos/patologia , Neutrófilos , Neoplasias Peritoneais/mortalidade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Taxa de Sobrevida
12.
Surg Pathol Clin ; 12(2): 457-479, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31097111

RESUMO

This review discusses select fallopian tube entities and their associated mimics. It first focuses on adenomatoid tumors, the most common benign tumor of the fallopian tube. High-grade serous carcinoma and its precursor, serous tubal intraepithelial carcinoma, are then addressed. Finally, attention is turned to endometrioid proliferations of the fallopian tube. A diagnostic approach is provided for these lesions, with an emphasis on differential diagnoses and situations in which a benign lesion may appear malignant, and vice-versa.


Assuntos
Tumor Adenomatoide/patologia , Neoplasias das Tubas Uterinas/patologia , Tumor Adenomatoide/diagnóstico , Carcinoma in Situ/diagnóstico , Carcinoma in Situ/patologia , Cistadenocarcinoma Seroso/diagnóstico , Cistadenocarcinoma Seroso/patologia , Diagnóstico Diferencial , Neoplasias das Tubas Uterinas/diagnóstico , Neoplasias das Tubas Uterinas/secundário , Tubas Uterinas/patologia , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Mesotelioma/diagnóstico , Mesotelioma/patologia , Metaplasia/diagnóstico , Metaplasia/patologia
13.
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
15.
BMJ Case Rep ; 12(3)2019 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-30936339

RESUMO

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.


Assuntos
Poluentes Ocupacionais do Ar/efeitos adversos , Asbestos/efeitos adversos , Exposição Ambiental/efeitos adversos , Neoplasias Pulmonares/diagnóstico , Mesotelioma/diagnóstico , Exposição Ocupacional/efeitos adversos , Neoplasias Pleurais/diagnóstico , Adulto , Compensação e Reparação/legislação & jurisprudência , Exposição Ambiental/legislação & jurisprudência , Evolução Fatal , Humanos , Índia , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/mortalidade , Masculino , Mesotelioma/induzido quimicamente , Mesotelioma/mortalidade , Exposição Ocupacional/legislação & jurisprudência , Neoplasias Pleurais/induzido quimicamente , Neoplasias Pleurais/mortalidade , Indenização aos Trabalhadores/legislação & jurisprudência
16.
Medicine (Baltimore) ; 98(14): e14979, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30946324

RESUMO

BACKGROUND: Soluble mesothelin-related peptide (SMRP) is a widely studied tumor marker for diagnosing malignant pleural mesothelioma (MPM). This study discussed the diagnostic value of SMRPs in pleural effusion (PE) for MPM. METHODS: Medline, Embase, Web of Science, and Cochrane library system were systematically searched on the data of SMRPs in PE for MPM diagnosis. Pooled diagnostic sensitivity, specificity, and symmetric receiver operating characteristic curve were calculated. RESULTS: Thirteen studies fulfilled the inclusion criteria and a total of 3359 cases including 759 MPM cases, 1061 non-MM (malignant mesothelioma) malignant PE, and 1539 benign PE were brought into this meta-analysis. The pooled results of SMRPs in PE for diagnosing MPM were as follows: sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.68 (95% confidence interval [CI]: 0.64-0.72), 0.91 (95% CI: 0.86-0.94), 7.8 (95% CI: 5.0-12.0), 0.35 (95% CI: 0.31-0.40), and 22 (95% CI: 14-35), respectively. The area under the summary receiver operating characteristic curves (AUC) was 0.75 (95% CI: 0.72-0.80). Subgroup analyzes revealed that the AUC of cohort group using histological diagnosis could be improved to 0.86 (95% CI: 0.83, 0.89). The Deek's funnel plot asymmetry test showed no publication bias. CONCLUSION: Although the sensitivity of SMRPs was low, PE-SMRPs can be a good indicator of the existence of MPM.


Assuntos
Proteínas Ligadas por GPI/metabolismo , Neoplasias Pulmonares/metabolismo , Mesotelioma/metabolismo , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Derrame Pleural/metabolismo , Biomarcadores Tumorais/metabolismo , Exsudatos e Transudatos/metabolismo , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Mesotelioma/diagnóstico , Mesotelioma/patologia , Derrame Pleural/diagnóstico , Derrame Pleural/patologia , Derrame Pleural Maligno/diagnóstico , Derrame Pleural Maligno/metabolismo , Derrame Pleural Maligno/patologia , Neoplasias Pleurais/diagnóstico , Neoplasias Pleurais/metabolismo , Neoplasias Pleurais/patologia , Sensibilidade e Especificidade
17.
Int J Oncol ; 54(6): 2139-2148, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30942424

RESUMO

Malignant pleural mesothelioma (MPM) is a rare malignancy arising from the pleura that is difficult to diagnose, contributing to its dismal prognosis. Previously, we reported that the degree of microRNA (miR)­34b/c methylation in circulating DNA is associated with the development of MPM. Herein, we present a newly developed droplet digital PCR (ddPCR)­based assay for the detection of miR­34b/c methylation in circulating DNA in patients with MPM. We originally prepared two probes within a short amplicon of 60 bp, designing one from the positive strand and the other from the complementary strand. The two probes functioned cooperatively, and our established assay detected DNA methylation accurately in the preliminary validation. We subsequently verified this assay using clinical samples. Serum samples from 35 cases of MPM, 29 cases of pleural plaque and 10 healthy volunteers were collected from 3 different institutions and used in this study. We divided the samples into 2 groups (group A, n=33; group B, n=41). A receiver­operating characteristic curve analysis using the samples in group A determined the optimal cut­off value for the diagnosis of MPM, with a sensitivity of 76.9% and a specificity of 90%. On the other hand, the use of the same criterion yielded a sensitivity of 59.1% and a specificity of 100% in group B, and corresponding values of 65.7 and 94.9% for the entire cohort, indicating a moderate sensitivity and a high specificity. In addition, when the analysis was focused on stage II or more advanced MPM, the sensitivity improved to 81.8%, suggesting the possibility that the methylated allele frequency in MPM may be associated with the stage of disease progression. On the whole, the findings of this study indicate that miR­34b/c methylation in circulating DNA is a promising biomarker for the prediction of disease progression in patients with MPM.


Assuntos
Biomarcadores Tumorais/genética , Ácidos Nucleicos Livres/metabolismo , Neoplasias Pulmonares/diagnóstico , Mesotelioma/diagnóstico , MicroRNAs/genética , Neoplasias Pleurais/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Ácidos Nucleicos Livres/isolamento & purificação , Metilação de DNA/genética , Progressão da Doença , Estudos de Viabilidade , Feminino , Humanos , Biópsia Líquida/métodos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Mesotelioma/sangue , Mesotelioma/genética , Mesotelioma/patologia , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Neoplasias Pleurais/sangue , Neoplasias Pleurais/genética , Neoplasias Pleurais/patologia , Reação em Cadeia da Polimerase/métodos , Prognóstico , Sensibilidade e Especificidade
18.
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
19.
Medicine (Baltimore) ; 98(15): e15147, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30985689

RESUMO

RATIONALE: Malignant mesothelioma is a malignant tumor with poor prognosis, which usually originates in the pleura, peritoneum, and pericardial cavity. Mesotheliomas that originate from the diaphragm are very rare. Here, we report a case of primary malignant mesothelioma of the diaphragm with liver invasion. PATIENT CONCERNS: A 66-year-old woman was admitted to our hospital because of a "liver space-occupying lesion," without any special clinical symptoms. Imaging examinations suggested a cystic-solid mixed lesion in the right lobe of the liver. DIAGNOSIS: The tumor was diagnosed as epithelioid mesothelioma of the diaphragm with liver invasion. INTERVENTION: The patient underwent abdominal surgery in our hospital to remove the diaphragmatic mass, liver mass, and part of the diaphragm. OUTCOMES: The postoperative course was uneventful. LESSONS: Primary diaphragmatic malignant mesothelioma is very rare and may involve liver or lung tissue and be mistaken for liver or lung tumor. Accurate diagnosis depends on careful pathological examination. Immunohistochemical staining is very useful to distinguish this tumor from other liver or diaphragmatic tumors.


Assuntos
Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/patologia , Mesotelioma/patologia , Neoplasias Musculares/patologia , Idoso , Diagnóstico Diferencial , Diafragma , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/cirurgia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/cirurgia , Mesotelioma/diagnóstico , Mesotelioma/cirurgia , Neoplasias Musculares/diagnóstico , Neoplasias Musculares/cirurgia
20.
JAMA Netw Open ; 2(4): e192597, 2019 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-31026023

RESUMO

Importance: A molecular diagnostic method that incorporates information about the transcriptional status of all genes across multiple tissue types can strengthen confidence in cancer diagnosis. Objective: To determine the practical use of a whole transcriptome-based pan-cancer method in diagnosing primary and metastatic cancers and resolving complex diagnoses. Design, Setting, and Participants: This cross-sectional diagnostic study assessed Supervised Cancer Origin Prediction Using Expression (SCOPE), a machine learning method using whole-transcriptome RNA sequencing data. Training was performed on publicly available primary cancer data sets, including The Cancer Genome Atlas. Testing was performed retrospectively on untreated primary cancers and treated metastases from volunteer adult patients at BC Cancer in Vancouver, British Columbia, from January 1, 2013, to March 31, 2016, and testing spanned 10 822 samples and 66 output classes representing untreated primary cancers (n = 40) and adjacent normal tissues (n = 26). SCOPE's performance was demonstrated on 211 untreated primary mesothelioma cancers and 201 treatment-resistant metastatic cancers. Finally, SCOPE was used to identify the putative site of origin in 15 cases with initial presentation as cancers with unknown primary of origin. Results: A total of 10 688 adult patient samples representing 40 untreated primary tumor types and 26 adjacent-normal tissues were used for training. Demographic data were not available for all data sets. Among the training data set, 5157 of 10 244 (50.3%) were male and the mean (SD) age was 58.9 (14.5) years. Testing was performed on 211 patients with untreated primary mesothelioma (173 [82.0%] male; mean [SD] age, 64.5 [11.3] years); 201 patients with treatment-resistant cancers (141 [70.1%] female; mean [SD] age, 55.6 [12.9] years); and 15 patients with cancers of unknown primary of origin; among the treatment-resistant cancers, 168 were metastatic, and 33 were the primary presentation. An accuracy rate of 99% was obtained for primary epithelioid mesotheliomas tested (125 of 126). The remaining 85 mesotheliomas had a mixed etiology (sarcomatoid mesotheliomas) and were correctly identified as a mixture of their primary components, with potential implications in resolving subtypes and incidences of mixed histology. SCOPE achieved an overall mean (SD) accuracy rate of 86% (11%) and F1 score of 0.79 (0.12) on the 201 treatment-resistant cancers and matched 12 of 15 of the putative diagnoses for cancers with indeterminate diagnosis from conventional pathology. Conclusions and Relevance: These results suggest that machine learning approaches incorporating multiple tumor profiles can more accurately identify the cancerous state and discriminate it from normal cells. SCOPE uses the whole transcriptomes from normal and tumor tissues, and results of this study suggest that it performs well for rare cancer types, primary cancers, treatment-resistant metastatic cancers, and cancers of unknown primary of origin. Genes most relevant in SCOPE's decision making were examined, and several are known biological markers of respective cancers. SCOPE may be applied as an orthogonal diagnostic method in cases where the site of origin of a cancer is unknown, or when standard pathology assessment is inconclusive.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias/diagnóstico , Transcriptoma , Sequenciamento Completo do Exoma/métodos , Adulto , Estudos Transversais , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Aprendizado de Máquina , Masculino , Mesotelioma/diagnóstico , Mesotelioma/genética , Pessoa de Meia-Idade , Neoplasias/genética
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