A case of malignant peritoneal mesothelioma / 中华劳动卫生职业病杂志

Malignant mesothelioma is a highly malignant disease that most often occurs in the pleural cavity, followed by the peritoneum and pericardium. Malignant peritoneal mesothelioma (MPM) accounts for 10%-15% of all mesothelioma. The most important risk factor for MPM is exposure to asbestos. MPM has no specific clinical symptoms, imaging and histopathology are critical for the diagnosis. There are currently no generally accepted guidelines for curative treatment of MPM. The patient mainly presented with abdominal pain, abdominal distension and discomfort. Due to extensive omentum metastasis, no further surgical treatment was performed. Pemetrexed combined with cisplatin chemotherapy was given for 2 cycles, and the patient is still alive.

Expression of CD24 gene in human malignant pleural mesothelioma and its relationship with prognosis / 中华劳动卫生职业病杂志

Objective: To investigate the expression of CD24 gene in human malignant pleural mesothelioma (MPM) cells and tissues, and evaluate its relationship with clinicopathological characteristics and clinical prognosis of MPM patients. Methods: In February 2021, UALCAN database was used to analyze the correlation between CD24 gene expression and clinicopathological characteristics in 87 cases of MPM patients. The TIMER 2.0 platform was used to explore the relationship between the expression of CD24 in MPM and tumor immune infiltrating cells. cBioportal online tool was used to analyze the correlation between CD24 and MPM tumor marker gene expression. RT-qPCR was used to analyze the expressions of CD24 gene in human normal pleural mesothelial cell lines LP9 and MPM cell lines NCI-H28 (epithelial type), NCI-H2052 (sarcoma type), and NCI-H2452 (biphasic mixed type). RT-qPCR was performed to detect the expressions of CD24 gene in 18 cases of MPM tissues and matched normal pleural tissues. The expression difference of CD24 protein in normal mesothelial tissue and MPM tissue was analyzed by immunohistochemistry. A Kaplan-Meier model was constructed to explore the influence of CD24 gene expression on the prognosis of MPM patients, and Cox regression analysis of prognostic factors in MPM patients was performed. Results: The CD24 gene expression without TP53 mutation MPM patients was significantly higher than that of patients in TP53 mutation (P<0.05). The expression of CD24 gene in MPM was positively correlated with B cells (r(s)=0.37, P<0.001). The expression of CD24 gene had a positive correlation with the expressions of thrombospondin 2 (THBS2) (r(s)=0.26, P<0.05), and had a negative correlation with the expression of epidermal growth factor containing fibulin like extracellular matrix protein 1 (EFEMP1), mesothelin (MSLN) and calbindin 2 (CALB2) (r(s)=-0.31, -0.52, -0.43, P<0.05). RT-qPCR showed that the expression level of CD24 gene in MPM cells (NCI-H28, NCI-H2052 and NCI-H2452) was significantly higher than that in normal pleural mesothelial LP9 cells. The expression level of CD24 gene in MPM tissues was significantly higher than that in matched normal pleural tissues (P<0.05). Immunohistochemistry showed that the expressions of CD24 protein in epithelial and sarcoma MPM tissues were higher than those of matched normal pleural tissues. Compared with low expression of CD24 gene, MPM patients with high expression of CD24 gene had lower overall survival (HR=2.100, 95%CI: 1.336-3.424, P<0.05) and disease-free survival (HR=1.800, 95%CI: 1.026-2.625, P<0.05). Cox multivariate analysis showed that compared with the biphasic mixed type, the epithelial type was a protective factor for the prognosis of MPM patients (HR=0.321, 95%CI: 0.172-0.623, P<0.001). Compared with low expression of CD24 gene, high expression of CD24 gene was an independent risk factor for the prognosis of MPM patients (HR=2.412, 95%CI: 1.291-4.492, P=0.006) . Conclusion: CD24 gene and protein are highly expressed in MPM tissues, and the high expression of CD24 gene suggests poor prognosis in MPM patients.

Mesotelioma pleural maligno. Actualización sobre diagnóstico y tratamiento / Malignant pleural mesothelioma. Update on diagnosis and treatment

RESUMEN Introducción: El mesotelioma pleural maligno es un tumor maligno primario de la pleura, comúnmente asociado con la exposición al asbesto. Se considera una patología rara y muy agresiva. Objetivo: Realizar una revisión sobre los criterios de diagnóstico y tratamiento actualizados en torno al mesotelioma pleural maligno. Métodos: Se realizó una revisión bibliográfica en fuentes de información disponibles en la Biblioteca Virtual de Salud, de la red telemática Infomed, entre ellas, las bases de datos SciELO, Pubmed/Medline, Cumed, Lilacs, así como el Google Académico. Se seleccionaron un total de 39 referencias. Conclusiones: Existen pocas referencias en la literatura nacional relacionadas con el diagnóstico, tratamiento y seguimiento de los pacientes con mesotelioma pleural maligno. El diagnóstico combina el uso del método clínico, los estudio imagenológicos e histoquímicos. No existe un tratamiento estándar, siendo recomendable un enfoque individualizado que combine según cada caso, cirugía, quimio y radioterapia. Los desafíos futuros incluyen el desarrollo de nuevas alternativas terapéuticas(AU)

ABSTRACT Introduction: Malignant Pleural Mesothelioma is a primary malignant tumor of the pleura, commonly associated with exposure to asbestos. It is considered a rare and very aggressive pathology. Objective: Conduct a review of updated diagnostic and treatment criteria for malignant pleural mesothelioma. Material and Methods: A bibliographic review was made through the search of information in sources available from the Cuban National Health Care Network and Portal (INFOMED), among them, databases such as SciELO, Pubmed / Medline, Cumed, Lilacs, as well as Google Scholar. Finally, a total of 39 references were selected for our study. Conclusions: There are few references in the national literature related to the diagnosis, treatment and follow-up of patients with malignant pleural mesothelioma. The diagnosis combines the use of the clinical method, the imaging and histochemical studies. There is no standard treatment, being recommended an individualized approach that combines according to each case, surgery, chemo and radiotherapy. Future challenges include the development of new therapeutic alternatives(AU)

Real-time PCR assay for the diagnosis of pleural tuberculosis / Reacción en cadena de la polimerasa en tiempo real para el diagnóstico de tuberculosis pleural

Abstract Introduction: The diagnosis of pleural tuberculosis requires an invasive and time-consuming reference method. Polymerase chain reaction (PCR) is rapid, but validation in pleural tuberculosis is still weak. Objective: To establish the operating characteristics of real-time polymerase chain reaction (RT-PCR) hybridization probes for the diagnosis of pleural tuberculosis. Methods: The validity of the RT-PCR hybridization probes was evaluated compared to a composite reference method by a cross-sectional study at the Hospital Universitario de la Samaritana. 40 adults with lymphocytic pleural effusion were included. Pleural tuberculosis was confirmed (in 9 patients) if the patient had at least one of three tests using the positive reference method: Ziehl-Neelsen or Mycobacterium tuberculosis culture in fluid or pleural tissue, or pleural biopsy with granulomas. Pleural tuberculosis was ruled out (in 31 patients) if all three tests were negative. The operating characteristics of the RT-PCR, using the Mid-P Exact Test, were determined using the OpenEpi 2.3 Software (2009). Results: The RT-PCR hybridization probes showed a sensitivity of 66.7% (95% CI: 33.2%-90.7%) and a specificity of 93.5% (95% CI: 80.3%-98.9%). The PPV was 75.0% (95% CI: 38.8%-95.6%) and a NPV of 90.6% (95% CI: 76.6%-97.6%). Two false positives were found for the test, one with pleural mesothelioma and the other with chronic pleuritis with mesothelial hyperplasia. Conclusions: The RT-PCR hybridization probes had good specificity and acceptable sensitivity, but a negative value cannot rule out pleural tuberculosis.

Resumen Introducción: El diagnóstico de tuberculosis pleural requiere un método de referencia invasivo y demorado. La reacción en cadena de la polimerasa es rápida, pero su validación en tuberculosis pleural aún es débil. Objetivo: Establecer las características operativas de la reacción en cadena de la polimerasa en tiempo real (RT-PCR) sondas de hibridación para el diagnóstico de tuberculosis pleural. Métodos: Se evaluó la validez de la RT-PCR sondas de hibridación comparada con un método de referencia compuesto mediante un estudio transversal en el Hospital Universitario de la Samaritana. Se incluyeron 40 adultos con derrame pleural linfocitario. Tuberculosis pleural fue confirmada (en 9 pacientes) si el paciente tenía mínimo una de tres pruebas del método de referencia positiva: Ziehl-Neelsen o cultivo para Mycobacterium tuberculosis en líquido o tejido pleural, o biopsia pleural con granulomas; se descartó tuberculosis pleural (en 31 pacientes) si las tres pruebas eran negativas. Se determinaron las características operativas de la RT-PCR, mediante la Prueba Mid-P Exact, con el Software OpenEpi 2.3 (2009). Resultados: La RT-PCR sondas de hibridación mostró una sensibilidad del 66.7% (IC 95%: 33.2%-90.7%) y una especificidad del 93.5% (IC 95%: 80.3%-98.9%). El VPP fue de 75.0% (IC 95%: 38.8%-95.6%) y un VPN de 90.6% (IC 95%: 76.6%-97.6%). Se encontraron dos falsos positivos para la prueba, uno con mesotelioma pleural y otro con pleuritis crónica con hiperplasia mesotelial. Conclusiones: La RT-PCR sondas de hibridación tuvo una buena especificidad y una aceptable sensibilidad, pero un valor negativo no puede descartar tuberculosis pleural.

Mesotelioma pleural maligno en ocho pacientes y revisión del tema / Malignant pleural mesothelioma in eight patients and review of topic

Se actualizan aspectos etiopatogénicos, clínicos, diagnósticos y terapéuticos en el mesotelioma pleural maligno, enfermedad temida e infrecuente en nuestro medio. Nos impresionó sobremanera, una profesional de salud tratada recientemente y en etapa temprana que apenas sobrevivió un año. El objetivo es elevar el conocimiento sobre el tema para tratar de mejorar la sobrevida. Se presentan una síntesis de ocho pacientes estudiados y tratados con este diagnóstico en los hospitales "Amalia Simoni", "Manuel Ascunce Domenech", "Madam Curie" de Camagüey y el "Martín Chang Puga" de Nuevitas desde 1998 hasta 2015, señalando el cuadro clínico, exámenes complementarios, diagnóstico, tratamiento médico quirúrgico y los resultados. Más de la mitad de los pacientes eran fumadores con pequeño derrame pleural inicial que hicieron pensar en la enfermedad, todo lo contrario cuando no existió derrame. Hubo tres enfermos donde el diagnóstico nos sorprendió por lo inesperado. La sobrevida fue baja con una media alrededor de 11 meses, solo uno vivió dos años. Los complementarios utilizados se ajustan a otros reportes y nuestras posibilidades. El tratamiento fue actualizado y acorde a otras series en el momento del diagnóstico. Se compara nuestra casuística, la cual se asemeja a publicaciones foráneas en cuanto a diagnóstico, tratamiento y sobrevida. Señalamos que, independiente de algunos recursos desde el punto de vista diagnóstico y terapéutico con que no contamos, los resultados se ajustan a la literatura actual y la sobrevida lograda fue sin dudas, adversa(AU)

Several etiopathogenetic, clinical, diagnostic and therapeutic aspects of the malignant pleural mesothelioma, fearful and infrequent disease in our context, are updated. It was really impressive the case of a female health professional that was recently treated at early stage of disease and barely survived one year. The objective of this review was to raise the level of knowledge on this disease in oder to improve survival rates. To this end, eight patients with this diagnosis, who were studied and treated in "Amalia Simoni", "Manuel Ascunce Domenech", "Madame Curie" hospitals in Camaguey and in "Martin Chang Puga" in Nuevitas from 1998 to 2015 were presented. Their clinical picture, supplementary tests, diagnosis, medical and surgical treatment and final results were described. Half of them were smokers with initial small pleural effusion that made the specialists suspect the existence of the disease. There were three patients whose diagnoses surprised the physicians because they were unexpected. Survival was low and the average survival rate was 11 months, although one managed to live two years. The indicated supplementary tests were similar to those of other reports and adjusted to our setting. Treatment was updated and consistent with other series at the time of diagnosis. The casuistry in our conditions was compared to others and it was similar in terms of diagnosis, treatment and survival rates to the one shown in foreign publication. Regardless of some unavailable diagnostic and therapeutic resources, the results of the treatment agree with those of the current literature on the topic and the survival rate was undoubtedly negative(AU)

Aspectos diagnósticos y terapéuticos en el mesotelioma pleural maligno / Diagnostic and therapeutic aspects in malignant pleural mesothelioma

Para el diagnóstico de mesotelioma se requiere distinguir entre afectación mesotelial benigna y maligna, y entre mesotelioma maligno y carcinoma metastásico. Para ello son necesarias técnicas inmuno-histoquímicas realizadas sobre biopsias amplias. La toracoscopia es la técnica de elección, aunque la biopsia con aguja usando técnicas de imagen en tiempo real puede ser muy útil si hay marcado engrosamiento nodular. Es improbable que la cirugía radical (pleuroneumonectomía) sea realmente curativa, por lo que está ganando adeptos la reducción de masa tumoral mediante pleurectomía/decorticación, con asociación de quimioterapia y radioterapia a la cirugía (terapia multimodal). Cuando la resección no es factible se plantea quimioterapia, con pleurodesis o colocación de un catéter pleural tunelizado si se requiere el control del derrame pleural y se reserva la radioterapia para tratar la infiltración de la pared torácica. También es esencial un completo control del dolor (que adquiere particular protagonismo en esta neoplasia) en unidades especializadas.

Diagnosis of malignant pleural mesothelioma requires making the distinction between benign mesothelial hiperplasia and true mesothelioma, and between malignant mesothelioma and metastatic pleural adenocarcinoma. This involves immunohisto-chemical techniques applied on large biopsy specimens, and thoracoscopy is the best choice for obtaining them. Real-time image-guided needle biopsy can also be very helpful in presence of marked nodular pleural thickening. Radical surgery (ie, extrapleural pneumonectomy) is unlikely to cure completely the patient, and cyto-reduction surgery with preservation of the underlying lung (pleurectomy/decortication), with addition of chemo and radiation therapy (muiltimodal treatment) is gaining adepts in the last few years. When surgery is not feasible at all, early chemotherapy -with pleurodesis or placement of a indwelling pleural catheter (to control the effusion if necessary)- is advisable. Radiation therapy should be reserved to treat chest wall infiltration in those cases, and complete control of pain in specialized units is also essential in those patients.

Mesotelioma bem diferenciado (benigno) de túnica vaginal: relato de um caso e revisão da literatura / Well-differentiated (benign) mesothelioma of the tunica vaginalis: report of a case and literature review

Mesoteliomas são tumores oriundos das células mesoteliais da pleura, peritônio, pericárdio ou túnica vaginal, sendo a exposição prolongada ao asbesto o principal fator de risco. Neoplasias mesoteliais benignas da região paratesticular são raras. Relata-se um caso de Mesotelioma de Túnica Vaginal associado à hidrocele, destacando a utilidade da ecografia na avaliação das massas escrotais (AU)

Mesotheliomas are tumors originating from the mesothelial cells of the pleura, peritoneum, pericardium or tunica vaginalis, with prolonged exposure to asbestos the main risk factor. Benign mesothelial neoplasms of the paratesticular region are rare. Here we report a case of tunica vaginalis mesothelioma associated with hydrocele, highlighting the usefulness of ultrasound in the evaluation of scrotal masses (AU)

Dificuldades no diagnóstico diferencial entre mesotelioma pleural e adenocarcinoma metastático para pleura patológica / Difficulties in the differential diagnosis between pleural mesothelioma and metastatic adenocarcinoma for pathological pleura

As dificuldades diagnósticas entre mesotelioma pleural e adenocarcinoma metastático na pleura exigem estudo amplo. Os autores ilustram um caso clínico cujo diagnóstico só foi estabelecido após realização de toracotomia, com retirada de material para análise imuno-histoquímica. A diferenciação diagnóstica é de fundamental importância, uma vez que envolvem conduta terapêutica e prognóstico distintos. O estudo adequado deve utilizar material obtido através de toracoscopia ou toracotomia e empregar coloração imuno-histoquímica, estudos com anticorpos monoclonais, microscopia eletrônica e pesquisa de marcadores tumorais.

The diagnosis difficulties distinguishing mesothelioma from pleural metastatic adenocarcinoma request wide study. The authors illustrate a clinical case whose diagnosis was only established after thoracotomy removing material for immune-histochemical analysis. The diagnosis differentiating is very important, because involves distinct treatment and prognosis. The appropriate study should use material obtained through thoracoscopy or thoracotomy and submitted to immune-histochemical coloration, studies with monoclonal antibodies, electronic microscopy and research of tumor makers.

Evaluation of the sensitivity and specificity of immunohistochemical markers in the differential diagnosis of effusion cytology

To evaluate the sensitivity and specificity of Calretinin and Carcinoembryonic antigen as immunocytochemical markers in distinguishing mesothelial cells from metastatic adenocarcinoma cells in effusion cytology. This study included 50 patients who presented with effusions [26 pleural and 24 peritoneal], at Al-Kadhimya Teaching Hospital who were selected according to their preliminary diagnosis from 1[st] December 2010 to 30[th] June 2011. Effusion fluids were aspirated and processed for both conventional cytological methods using Papanicolaou-stain and immunocytochemical staining with anti Calretinin and Carcinoembryonic antigen. The sensitivity of cytology for detection of malignant cells was 77%, with 100% specificity and 86% accuracy. Calretinin was observed to be a specific [100%] and sensitive [90%] marker for mesothelial cells [of benign etiology]. Carcinoembryonic antigen exhibited 70% sensitivity and 100% specificity for adenocarcinoma cells. When the results of both cytology and immunocytochemistry were considered in conjunction, the sensitivity for the detection of malignancy increased to 97%, with 100% specificity and 98% accuracy. Calretinin and Carcinoembryonic antigen were found to be useful markers for differentiating reactive mesothelial cells from metastatic adenocarcinoma cells in smears prepared from body fluids. Also, the combination of both cytology and immunocytochemical studies using the two markers can greatly enhance the diagnostic accuracy, sensitivity and specificity in malignant effusions.

Determinación de péptidos solubles relacionados a mesotelina para la detección precoz del mesotelioma maligno / Soluble mesothelin-related protein for malignant pleural mesothelioma screening

Introduction: Malignant Pleural Mesothelioma (MPM) is a tumor of the mesothelial cells related to asbestos exposure. This malignancy is extremely aggressive, with poor response to different treatment modalities, and it has a mean survival of 8 months since diagnosis. With the introduction of new chemotherapeutic agents and trimodality protocols, five-year survival of 40 percent in initial stages has been reported. Serum detection of Soluble Mesothelin-related Protein (SMRP) could be used for screening of MPM. Using the MESOMARK® test, 53 percent of MPM patients had levels greater than 1,5 nM, while 99 percent of control patients had lower concentrations. The aim of this study is to evaluate the use of this test in Chile and determine its utility for screening ofMPM. Methods: Quantitative blind measurement of serum SMRP by MESOMARK® test. We studied 3 groups: 8 workers exposed to asbestos, 5 patients with diagnosed MPM and 14 age matched workers without known exposure to asbestos. Participants were informed of the study. Results: Mean +/- standard deviation SMRP levels in the control group was 0,53 +/- 0,4 nM, 0,89 +/- 0,46 nM in patients exposed to asbestos and 10,68 +/- 10,28 nM in MPMpatients. Differences between the groups were statistically significant (p = 0,02). In the MPM group, 3 patients were found to have SMRP levels greater than 1,5 nM (17,27 nM; SD 6,95) and 2 patients normal values (0,79 nM; SD 0,32). Using a cut-off value of 1,5 nM, sensitivity of the test was 60 percent and specificity was 100 percent. Conclusions: Detection of SMRP levels allowed to identify patients with MPM, three of whom had very high concentrations. The sensitivity and specificity found is similar to that previously reported. If our results are confirmed in greater studies, SMRP detection could be used for screening of MPM.

Resumen Introducción: El Mesotelioma Maligno (MM) es un tumor de las células mesoteliales relacionado a la exposición a asbesto, altamente agresivo, con pobre respuesta al tratamiento y con una sobrevida promedio de 8 meses después del diagnóstico. Sin embargo, nuevos agentes quimioterapéuticos y protocolos de terapia trimodal han logrado sobrevidas de hasta 40 por ciento en etapas iniciales. La detección en sangre periférica de Péptidos Solubles Relacionados a Mesotelina (SMRP) podría ser útil para el diagnóstico precoz de MM. Utilizando el test MESOMARK® para la determinación de SMRP, 53 por ciento de los pacientes con MM tenían valores mayores a 1,5 nM mientras que 99 por ciento de los controles mostraron valores inferiores. El objetivo del presente trabajo es evaluar la implementación de este test en Chile y determinar su utilidad para el diagnóstico precoz en MM. Métodos: Medición cuantitativa de SMRP en suero humano por test MESOMARK®. Se realizaron mediciones en forma ciega a 8 trabajadores con exposición a asbesto, a 5 pacientes con MMy a 14 voluntarios sin exposición. Todos los participantes fueron informados del estudio. Resultados: El promedio +/- desviación estándar de SMRP en el grupo control fue de 0,53 +/- 0,4 nM, de 0,89 +/- 0,46 nM en los expuestos sin MMy de 10,68 +/- 10,28 nM en el grupo con MM; encontrándose una diferencia estadísticamente significativa entre los valores de estos tres grupos (p = 0,02). En el grupo con MM, 3 pacientes tuvieron concentraciones mucho mayores a 1,5 nM (17,27 nM; DS 6,95) y 2 valores normales (0,79 nM; DS 0,32). Utilizando un valor de 1,5 nM como punto de corte, la sensibilidad fue de 60 por ciento y la especificidad de 100 por ciento. Conclusiones: La medición de SMRP permitió diferenciar a los pacientes con MM, presentando 3 de ellos concentraciones muy elevadas. La sensibilidad y especificidad encontrada es similar con datos previamente reportados. De confirmarse estos resultados en estudios con mayor ...

Epithelioid malignant mesothelioma of tunica vaginalis with deciduoid features: An unusual malignancy clinically masquerading an inguinal hernia.

Paratesticular/scrotal and inguinal canal mass lesions in elderly patients may pose a diagnostic challenge to both the surgeon as well as the pathologist. In most cases, these represent hernial sacs with their contents, and true neoplasms like lipomas, rhabdomyosarcomas, and fibrous pseudotumors are infrequent. Malignant mesotheliomas arising from the tunica layers are rare cause of inguinal and paratesticular tumors. Herein, we report a case of an elderly patient who presented with an inguinal hernia which pathologically had features of deciduoid malignant mesothelioma.

Combined blood and pleural levels of mesothelin and osteopontin for the diagnosis of malignant pleural mesothelioma

Malignant pleural mesothelioma [MPM] is a highly aggressive tumor with poor survival rate. It is difficult to diagnose MPM at an early stage. Soluble mesothelin remains the best available biomarker for MPM, however the lack of sensitivity for early stage disease provides a motivation for the search of an additional marker that could be combined with mesothelin for early malignancy detection. The aim was to evaluate the diagnostic value of soluble mesothelin and osteopontin both in blood and pleural fluid of MPM patients and to assess whether combination of these markers could improve the diagnostic accuracy of mesothelin. In this study mesothelin and osteopontin were measured by ELISA method in 197 samples [123 blood and 74 pleural] obtained from 123 participants, divided into 4 groups: 38 MPM patients, 24 patients with metastatic pleural effusion [Mets] of various carcinomas, 29 patients with hydrothorax and 32 healthy asbestos exposed subjects. Receiver operating characteristic [ROC] curves were generated to compare the diagnostic capability of these biomarkers. Combination of markers was done through logistic regression analysis. The median blood and pleural levels of the two markers were significantly higher in MPM patients than in hydrothorax or asbestos exposure groups [P < 0.0001], however the difference between MPM and Mets group was not significant. Combining the data from blood mesothelin and osteopontin using logistic regression model raised the area under the ROC curve [AUC] from 0.774 for serum mesothelin and 0.828 for plasma osteopontin to 0.867 to differentiate MPM from hydrothorax and asbestos exposed subjects. Combining the diagnostic capability of both pleural markers raised the AUC from 0.871 for pleural mesothelin and 0.847 for pleural osteopontin to 0.905 to differentiate MPM from hydrothorax patients. The performance of serum and pleural mesothelin in diagnosing MPM was improved when combined with plasma and pleural osteopontin [respectively] through logistic regression analysis model. This will be a great advance in screening and management of MPM