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Malignant mesothelioma of the tunica vaginalis is an extremely rare and aggressive tumor that is frequently encountered in elderly patients. The diagnosis of malignant mesothelioma of the tunica vaginalis poses a diagnostic challenge due to its infrequency and nonspecific clinical presentation. Histopathological examination and immunohistochemical staining are essential in differentiating this tumor from other para-testicular masses and establishing a definitive diagnosis. Early detection and comprehensive treatment planning are crucial for improving the prognosis and overall outcomes for patients with this rare malignancy. We present a report of malignant mesothelioma of the tunica vaginalis in a 78-year-old male patient with no history of asbestos exposure who presented with a large infiltrative left para-testicular mass. Histopathological examination revealed a biphasic proliferation composed of epithelioid and spindle cells with infiltrative features, foci of necrosis, and increased mitotic figures. Immunohistochemical staining exhibited positive staining for WT1, D2-40, and calretinin, supporting the mesothelial origin of the tumor. Notably, BerEP4 staining was negative, arguing against carcinoma. Immunostaining for keratin 5 was positive, supporting the mesothelial differentiation. The Ki67 proliferation index was high. The differential diagnosis included adenomatoid tumors, germ cell tumors, and pleomorphic sarcoma. We aim to discuss the clinical presentation, diagnostic approach, and therapeutic approaches of this rare entity. [ABSTRACT FROM AUTHOR]

Scrotal malignant mesothelioma is an aggressive tumor arising from the tunica vaginalis. Due to its rarity, this tumor is often accidentally found during histological evaluation and there are no recommendations for treatment. Based on three case presentations we try to draw attention for this rare disease and highlight the importance of referring these patients to a tertiary center. [ABSTRACT FROM AUTHOR]

Malignant mesothelioma is a rare tumor associated with asbestos exposure. Mesothelioma carcinogenesis is related to enhanced reactive oxygen species (ROS) production and iron overload. Despite the recent advances in biomedical sciences, to date the only available treatments include surgery in a small fraction of patients and platinum-based chemotherapy in combination with pemetrexed. In this view, the purpose of this study was to evaluate the therapeutic potential of the newly synthetized platinum prodrug Pt(IV)Ac-POA compared to cisplatin (CDDP) on human biphasic mesothelioma cell line MSTO-211H using different complementary techniques, such as flow-cytometry, transmission electron microscopy (TEM), and immunocytochemistry. Healthy mesothelial cell lines Met-5A were also employed to assess the cytotoxicity of the above-mentioned compounds. Our in vitro results showed that Pt(IV)Ac-POA significantly interfere with iron metabolisms and more importantly is able to trigger cell death, through different pathways, including ferroptosis, necroptosis, and apoptosis, in neoplastic cells. On the other hand, CDDP triggers mainly apoptotic and necrotic cell death. In conclusion, Pt(IV)Ac-POA may represent a new promising pharmacological agent in the treatment of malignant mesothelioma. [ABSTRACT FROM AUTHOR]

Indole‐based agents are frequently used in targeted or supportive therapy of several cancers. In this study, we investigated the anticancer properties of originally synthesized novel indolin‐2‐one derivatives (6a‐d) against Malignant Mesothelioma, Breast cancer, and Colon Cancer cells. Our results revealed that all derivatives were effectively delayed cell proliferation by inhibiting the ERK1/2, AKT, and STAT3 signaling pathways in a concentration‐dependent manner. Additionally, these variants induced cell cycle arrest in the S phase, accompanied by elevated levels of p21 and p27 expressions. Derivatives also initiated mitochondrial apoptosis through the upregulation of Bax and downregulation of Bcl‐2 proteins, leading to the activation of caspase 3 and PARP cleavage in exposed cells. Remarkably, three of the indolin‐2‐one derivatives displayed significant selectivity towards Breast and Colon Cancer cells, with compound 6d promising as the most potent and wide spectral one for all cancer cell lines. [ABSTRACT FROM AUTHOR]

We report a case of a 69‐year‐old woman with pleural mesothelioma presenting in the posterior mediastinum with a maximum diameter of 25 cm. She had a chronic cough and a pleural effusion was noted on chest X‐ray. The examination of the effusion showed high hyaluronic acid levels, and mesothelioma was suspected. A chest computed tomography scan showed a huge mediastinal mass, which caused rapid progression of respiratory failure and compression of the heart. Sufficient tissue samples could not be obtained before death. The patient died approximately 1 month after the initial visit, and a pathological autopsy was performed. The diagnosis of malignant pleural mesothelioma was made. Malignant pleural mesothelioma with a huge posterior mediastinal mass such as in this case is considerably rare; however, it is a rapidly progressing form of the disease and is reported here as an important differential diagnosis for mediastinal tumours. [ABSTRACT FROM AUTHOR]

Background: Malignant mesothelioma (MM) is a rare but lethal cancer strongly associated with asbestos exposure. This retrospective study examines mesothelioma trends and past asbestos exposure assessment in Emilia-Romagna, Northern Italy. Methods: Between 1996 and 2023, 3,513 cases of MM were recorded by the Regional Operating Center, predominantly in males (72%) and older than 65 years (79%). MM diagnosis was defined as certain, probable, and possible. Information concerning asbestos exposure was collected through an analytical questionnaire administered to patients or proxies and classified as occupational and non-occupational. Results: Occupational exposure accounted for 82% of cases, significantly increasing from 71% to 88% in the most recent period. A more accurate definition of occupational exposure indicates that specific exposure has gone from 49% in the first period to 62% and 58% in the last two periods; probable exposure decreased from 21% to 16%, while possible exposure decreased from 16% to 13%. Familiar exposure remained relatively constant at around 8%, environmental exposure slightly decreased from 4% to 2%, while non-occupational exposure remained stable at 2%. Among patients with exclusively occupational exposure (1,826 cases), 87% were male and aged between 65 and 75 years (36%) and 75+ (41%). Exposure rates for the province of residence see the province of Reggio Emilia with the highest occupational exposure rate (2.5 x 100,000 residents), followed by Ravenna (2.3 x 100,000 residents) and Parma and Piacenza, which have similar exposure rates with 2.2 x 100,000 residents. Occupational sectors such as construction, railway maintenance, and metalworking are identified as high-risk industries. Despite efforts to mitigate exposure, non-occupational and environmental exposures persist. The study highlights the importance of continuous surveillance and exposure monitoring to guide effective interventions and legal recognition of MM. [ABSTRACT FROM AUTHOR]

Objective: To provide the most up-to-date data on the burden of malignant mesothelioma (MM) and the projections through 2029 in China. Methods: Data on patients diagnosed with MM from China during 1990–2019 were obtained from the Global Burden of Disease (GBD) 2019 database, including annual cases and deaths data and age-standardized rates of incidence, mortality, and disability-adjusted life-years (DALYs) associated with MM among different age groups. Temporal trends during 1990–2019 were analyzed by the Joinpoint regression models using 95% confidence interval (CI), while the projections through 2029 were calculated by the Bayesian age-period-cohort model. Data on the production and consumption of asbestos in China were obtained from the United States Geological Survey on Mineral Commodity Summaries during 1996–2023. Results: We observed a significant elevation in incident new cases and deaths over the last 3 decades, increasing from 1193 in 1990 to 2815 in 2019 for incident cases and from 1134 in 1990 to 2773 in 2019 for death cases. We found a roughly 6% increase in the proportion of incident cases for those aged >70 years (30% in 2019 versus 24% in 1990), while for the proportion of deaths similar elevation for those aged >70 years was found. Additionally, men had significantly higher DALYs due to MM across age groups compared with women. Asbestos consumption in China dramatically dropped since 2012 and reached the bottom in 2017 with 230 kilotons. By 2029, the projected age-standardized rate for incidence and mortality is expected to reach 1.2 per million for both. Conclusion: We found, for the first time using GBD data on the Chinese population, that the burden of MM has been significantly increasing in China over the last three decades and will continue to increase in the upcoming decade, suggesting an urgent need for a complete ban on chrysotile asbestos in China.

Nodular soft tissue pleural thickening on imaging is highly suggestive of malignancy, of which pleural malignant mesothelioma and metastatic disease are differentials. We present the case of a 71-year-old male who presented with acute worsening of shortness of breath associated with a recurrent left pleural effusion post-pleurocentesis. He was an ex-smoker with previous asbestos exposure. Computed tomography performed demonstrated left-sided pleural thickening in the hemithorax and hemidiaphragm with complex pleural effusion. 18F‐2‐deoxy‐d‐glucose whole body PET scan revealed extensive uptake throughout the left hemithorax in multiple pleural masses. The imaging findings and clinical case were typical of malignant mesothelioma. However, histopathology results revealed small cell lung cancer. We need to be cognisant of this atypical presentation of a common disease entity. Even when all clinical and imaging findings point towards a certain diagnosis, histopathological assessment cannot be ignored.

Abstract Background Despite significant advancements in treatments such as surgery, radiotherapy, and chemotherapy, the survival rate for patients with asbestos-related cancers remains low. Numerous studies have provided evidence suggesting that air pollution induces oxidative stress and inflammation, affecting acute respiratory diseases, lung cancer, and overall mortality. However, because of the high case fatality rate, there is limited knowledge regarding the effects of air pollution exposures on survival following a diagnosis of asbestos-related cancers. This study aimed to determine the effect of air pollution on the survival of patients with malignant mesothelioma and asbestos-related lung cancer. Methods We followed up with 593 patients with malignant mesothelioma and 998 patients with lung cancer identified as asbestos victims between 2009 and 2022. Data on five air pollutants—sulfur dioxide, carbon monoxide, nitrogen dioxide, fine particulate matter with a diameter

Background: The incidence and mortality of pleural mesothelioma (PM) reflect the production and consumption of asbestos over time. However, despite the current global concern, these data remain to be known. Objective: Our aim was to carry out a descriptive analysis of PM cases and mortality from some Portuguese databases between 2014 and 2020. Methods: A retrospective observational study was carried out between 2014 and 2020. Data on the number of PM cases were provided by the Portuguese Cancer Registry, and data on mortality were from the Portuguese Death Certificate Information System. Results: Between 2014 and 2020, 315 cases of PM were reported, with 222 (70.5%) men. The average age of patients was 72.1, with the highest number of cases in patients aged >70 years (n = 198; 62.9%). The highest number of cases was reported in 2018 (n = 62; 19.7%). Regarding mortality, 169 deaths were reported, with 126 (74.6%) men and mostly in individuals aged >70 years (n = 109; 64.5%). It is estimated that around 520 years of potential life were lost. The highest number of deaths occurred in 2015 (n = 33; 19.5%). Conclusion: It is mandatory to reinforce the need for surveillance programs that allow us to gather real and reliable data and eliminate asbestos-related diseases. [ABSTRACT FROM AUTHOR]

The selection of highly specific target antigens is critical for the development of clinically efficient and safe chimeric antigen receptors (CARs). In search of diagnostic marker for malignant mesothelioma (MM), we have established SKM9‐2 monoclonal antibody (mAb) which recognizes a MM‐specific molecule, sialylated Protein HEG homolog 1 (HEG1), with high specificity and sensitivity. In this study, to develop a novel therapeutic approach against MM, we generated SKM9‐2 mAb‐derived CARs that included the CD28 (SKM‐28z) or 4‐1BB (SKM‐BBz) costimulatory domain. SKM‐28z CAR‐T cells showed continuous growth and enhanced Tim‐3, LAG‐3, and PD‐1 expression in vitro, which might be induced by tonic signaling caused by self‐activation; however, these phenotypes were not observed in SKM‐BBz CAR‐T cells. In addition, SKM‐BBz CAR‐T cells exhibited slightly stronger in vitro killing activity against MM cell lines than SKM‐28z CAR‐T cells. More importantly, only SKM‐BBz CAR‐T cells, but not SKM‐28z CAR‐T cells, significantly inhibited tumor growth in vivo in a MM cell line xenograft mouse model. Gene expression profiling and reporter assays revealed differential signaling pathway activation; in particular, SKM‐BBz CAR‐T cells exhibited enhanced NF‐kB signaling and reduced NFAT activation. In addition, SKM‐BBz CAR‐T cells showed upregulation of early memory markers, such as TCF7 and CCR7, as well as downregulation of pro‐apoptotic proteins, such as BAK1 and BID, which may be associated with phenotypical and functional differences between SKM‐BBz and SKM‐28z CAR‐T cells. In conclusion, we developed novel SKM9‐2‐derived CAR‐T cells with the 4‐1BB costimulatory domain, which could provide a promising therapeutic approach against refractory MM. [ABSTRACT FROM AUTHOR]

The diagnosis of mesothelioma has historically been challenging, especially on serous fluid cytology (SFC). Distinguishing between reactive and neoplastic mesothelial cells can be difficult on cytomorphology alone. However, additional ancillary tests, such as BRCA1 associated protein-1 immunohistochemistry and fluorescence in situ hybridization for cyclin-dependent kinase inhibitor 2A deletion, can provide a sensitive and highly specific method of proving malignancy. SFC specimens diagnosed as mesothelioma, suspicious for mesothelioma (SM), and atypical mesothelial cells (AMCs) since 2012 were identified by querying the laboratory information system. Clinical data and pathologic parameters were gathered. One hundred ten cases of mesothelioma, SM, and AMC were identified. Of these, 61 cases had a definitive diagnosis of mesothelioma on SFC. Average age at SFC diagnosis was 67 years (26-87 years), with most patients being male (67%). Out of the 61 cases, 11 cases (18%) had an initial diagnosis of mesothelioma made on SFC specimens, with 5 of these 11 cases being in patients that never received a histologic diagnosis of mesothelioma. Ancillary studies were utilized in all 11 cases. An initial diagnosis of metastatic mesothelioma was made on SFC in 9 cases (15%). For 6 of these 9 cases, the SFC diagnosis was the sole diagnosis of metastatic mesothelioma without a companion histologic diagnosis. In addition, 15 cases were diagnosed as SM, with 11 of these cases following a definitive mesothelioma diagnosis. Thirty-four cases were diagnosed as AMC, with 27 cases following a definitive mesothelioma diagnosis. The diagnosis of mesothelioma can be reliably made on SFC with the appropriate cytomorphology criteria and/or confirmatory ancillary testing. • Mesothelioma diagnosis requires distinction between benign and malignant mesothelium. • Ancillary tests provide sensitive and highly specific methods of proving malignancy. • Serous fluid cytology provides the potential for early mesothelioma diagnosis. • These specimens may be optimal in diagnosis of occult metastatic disease. [ABSTRACT FROM AUTHOR]

Background: The L-type amino acid transporter (LAT1) exhibits significantly increased expression within tumor cells across various neoplasms. However, the clinical significance of LAT1 expression in patients with pleural mesothelioma (PM) remains unclear. Methods: Eighty patients diagnosed with PM between June 2007 and August 2022, were eligible for this study. LAT1, alanine-serine-cysteine transporter 2 (ASCT2), Ki-67, and VEGFR2 were evaluated by immunohistochemistry. Inflammatory and nutritional indices were also correlated with different variables, including neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), systemic immune-inflammation index (SII), prognostic nutritional index (PNI), advanced lung cancer inflammation index (ALI), and Glasgow prognostic score (GPS). Results: LAT1 was highly expressed in 57.5 % of patients with PM. Among the 80 patients included in this study, 65 (81.3 %) received chemotherapy, either alone or followed by surgical resection, while 15 (18.7 %) opted for best supportive care. The level of LAT1 significantly correlated with cell proliferation and ASCT2. Factors such as performance status, histology, LAT1 expression, PNI, ALI, and GPS were significant prognostic indicators for progression-free survival (PFS), while Ki-67, LAT1, NLR, SII, PNI, ALI, and GPS were identified as significant predictors for overall survival (OS). LAT1 expression emerged as an independent prognostic factor for predicting PFS and OS in all patients, as well as in the subgroup of 65 patients receiving chemotherapy. Notably, high LAT1 expression proved to be a significant predictor of outcome, particularly in the subgroup with high PLR and SII. Conclusion: LAT1 was a significant predictor of outcomes in patients with PM and was more predictive of worse outcomes in patients with high inflammatory and low nutritional status.

Abstract We report a case of a 69‐year‐old woman with pleural mesothelioma presenting in the posterior mediastinum with a maximum diameter of 25 cm. She had a chronic cough and a pleural effusion was noted on chest X‐ray. The examination of the effusion showed high hyaluronic acid levels, and mesothelioma was suspected. A chest computed tomography scan showed a huge mediastinal mass, which caused rapid progression of respiratory failure and compression of the heart. Sufficient tissue samples could not be obtained before death. The patient died approximately 1 month after the initial visit, and a pathological autopsy was performed. The diagnosis of malignant pleural mesothelioma was made. Malignant pleural mesothelioma with a huge posterior mediastinal mass such as in this case is considerably rare; however, it is a rapidly progressing form of the disease and is reported here as an important differential diagnosis for mediastinal tumours.

Asbestos exposure has been proposed as a risk factor for shorter telomere length. The aim of our study was to investigate whether telomere length in leukocytes and hTERT genetic polymorphisms may serve as potential biomarkers for the risk of developing asbestos-related diseases and as biomarkers of progression and chemotherapy response rate in malignant mesothelioma (MM).

Paratesticular malignant mesothelioma (MM) is a rare tumor frequently associated with asbestos exposure. Therefore, we present an even rarer case of a 78-year-old male patient diagnosed with multiple primary neoplasms, including prostate cancer, lung cancer, paratesticular MM, and upper tract urothelial carcinoma. The patient initially presented with a painless testicular mass and had a notable medical history of prostate and lung cancers. Following physical examination and an ultrasound evaluation, he underwent radical right inguinal orchiectomy, which revealed paratesticular MM. The patient’s lung cancer recurrence and subsequent treatment coincided with periods of no MM recurrence. However, after the lung cancer treatment, the MM recurred multiple times within short intervals. This unique case indicates that systemic treatments for lung cancer, specifically cisplatin-based chemotherapy and atezolizumab immunotherapy, might also have an anti-tumor effect on paratesticular MM. Although MM combined with multiple primary neoplasms is challenging to treat and frequently recurs, treatments for other malignancies, as evidenced in this case, may have suppressive effects on the recurrence and metastasis of MM.

Reactive species are involved in various aspects of neoplastic diseases, including carcinogenesis, cancer-specific metabolism and therapeutics. Non-thermal plasma (NTP) can directly provide reactive species, by integrating atmospheric and interjacent molecules as substrates, to represent a handy strategy to load oxidative stress in situ. NTP causes apoptosis and/or ferroptosis specifically in cancer cells of various types. Plasma-activated Ringer's lactate (PAL) is another modality at the preclinical stage as cancer therapeutics, based on more stable reactive species. PAL specifically kills malignant mesothelioma (MM) cells, employing lysosomal ·NO as a switch from autophagy to ferroptosis. However, the entire molecular mechanisms have not been elucidated yet. Here we studied cytosolic iron regulations in MM and other cancer cells in response to PAL exposure. We discovered that cells with higher catalytic Fe(II) are more susceptible to PAL-induced ferroptosis. PAL caused a cytosolic catalytic Fe(II)-associated pathology through iron chaperones, poly (rC)-binding proteins (PCBP)1/2, inducing a disturbance in glutathione-regulated iron homeostasis. PCBP1/NCOA4-mediated ferritinophagy started at a later phase, further increasing cytosolic catalytic Fe(II), ending in ferroptosis. In contrast, PCBP2 after PAL exposure contributed to iron loading to mitochondria, leading to mitochondrial dysfunction. Therapeutic effect of PAL was successfully applied to an orthotopic MM xenograft model in mice. In conclusion, PAL can selectively sensitize MM cells to ferroptosis by remodeling cytoplasmic iron homeostasis, where glutathione and PCBPs play distinct roles, resulting in lethal ferritinophagy and mitochondrial dysfunction. Our findings indicate the clinical application of PAL as a ferroptosis-inducer and the potential of PCBPs as novel targets in cancer therapeutics. [Display omitted] • Cells with higher catalytic Fe(II) are more susceptible to PAL. • GSH coordinates with elevated cytosolic Fe(II) as catalytic part of labile iron pool. • PAL caused a cytosolic catalytic Fe(II)-associated pathology through iron chaperones. • PCBP2 carried excess cytosolic catalytic Fe(II) to mitochondria, causing ferroptosis. • Effect of PAL was demonstrated in an orthotopic MM xenograft model of mice. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The relationship between inflammatory markers and survival in many cancers has been investigated previously. Inflammatory markers may also offer the possibility of predicting surveillance in patients with malignant mesothelioma. Our study seeks to enhance comprehension of how variables such as the nutritional status and inflammation indices of malignant mesothelioma patients impact the disease's progression and prognosis. PATIENTS AND METHODS: This study included patients who were treated at the Erciyes University Medical Oncology Clinic between 2010 and 2022 and diagnosed with malignant mesothelioma. This is a retrospective single-center cohort study. Receiver Operating Characteristic (ROC) analysis was applied to determine the inflammation markers' optimal cutoff values with high sensitivity and specificity. Patients were categorized based on these values. The differences in overall survival (OS) and progression-free survival (PFS) between categorized groups were assessed using Log-rank curves and Kaplan-Meier tests. Multivariate analysis was performed using Cox regression analysis on statistically significant data. The relationship between inflammation markers and malignant mesothelioma survival was evaluated. RESULTS: There are 115 patients in this study. Pre-treatment high neutrophil to lymphocyte ratio (NLR) (HR: 1.34, 95% CI: 1.12-2.83, p=0.04), high pan-immune inflammation value (PIIV) (HR: 2.01, 95% CI: 1.32-4.79, p=0.03), and high systemic inflammation response index (SIRI) (HR: 1.34, 95% CI: 1.2-2.78, p=0.04) were associated with poor OS. Conversely, high advanced lung cancer inflammation index (ALI) (HR: 0.73, 95% CI: 0.53-0.84, p=0.03) and high hemoglobin-albumin-lymphocyte and platelet (HALP) (HR: 0.67, 95% CI: 0.23-0.78, p=0.02) were associated with favorable survival. CONCLUSIONS: Our study investigated the prognostic value of various inflammation markers in malignant mesothelioma patients and suggests that composite formulas like NLR, PIIV, SIRI, ALI, and HALP that incorporate CBC cells and nutritional parameters like albumin, height, and weight could more consistently and accurately predict malignant mesothelioma prognosis. [ABSTRACT FROM AUTHOR]

Malignant pleural mesothelioma (MPM) is a rare and aggressive tumor that leads to approximately 20,000 deaths per year. The most common symptoms are chest pain, shortness of breath, cough and weight loss. Radiologic studies usually reveal pleural thickening and pleural effusion, although the disease can also rarely present with spontaneous pneumothorax or hydropneumothorax. We present here a case of a 57-year-old male diagnosed with occult epithelioid type MPM based on video thoracoscopic (VATS) exploration and biopsy who experienced recurrent pneumothorax attacks and prolonged air leakage. Although there are few symptoms or imaging findings specific to MPM, elderly patients with recurrent pneumothorax attacks should be questioned for asbestos exposure, and MPM should be kept in mind in the differential diagnosis. [ABSTRACT FROM AUTHOR]

Calretinin is a promising diagnostic biomarker for malignant mesothelioma (MM), but less is known about its prognostic role. Our aim was to evaluate the association between serum calretinin concentration or genetic factors and the survival or outcome of cisplatin-based chemotherapy in MM. Our study included 265 MM patients. Serum calretinin concentration was determined using ELISA. Patients were genotyped for seven polymorphisms in CALB2, E2F2, MIR335, NRF1, and SEPTIN7 using competitive allele-specific PCR. Nonparametric tests, logistic regression, and survival analysis were used for statistical analysis. Higher serum calretinin concentration was associated with shorter progression-free (PFS) (HR = 1.18 (1.02–1.37), p = 0.023) and overall survival (OS) (HR = 1.20 (1.03–1.41), p = 0.023), but the association was not significant after adjusting for clinical factors (HR = 1.05 (0.85–1.31), p = 0.653 and HR = 1.06 (0.84–1.34), p = 0.613, respectively). SEPTIN7 rs3801339 and MIR335 rs3807348 were associated with survival even after adjustment (HR = 1.76 (1.17–2.64), p = 0.007 and HR = 0.65 (0.45–0.95), p = 0.028, respectively). Calretinin concentration was higher in patients who progressed after treatment with cisplatin-based chemotherapy (1.68 vs. 0.45 ng/mL, p = 0.001). Calretinin concentration above 0.89 ng/mL was associated with shorter PFS and OS from the start of chemotherapy (HR = 1.88 (1.28–2.77), p = 0.001 and HR = 1.91 (1.22–2.97), p = 0.004, respectively), even after adjusting for clinical factors (p < 0.05). MIR335 rs3807348 was associated with a better response to chemotherapy (OR = 2.69 (1.17–6.18), p = 0.020). We showed that serum calretinin is associated with survival and chemotherapy treatment outcomes in MM and could serve as a predictive biomarker. [ABSTRACT FROM AUTHOR]

Malignant mesothelioma and asbestos-related lung cancer are typically associated with a poor prognosis. However, it has been observed that some patients with these cancers survive significantly longer than the average survival period. While many preliminary studies have investigated factors influencing patient survival, the specific impact of asbestos exposure has not been thoroughly explored. We followed up with 546 patients with malignant mesothelioma and 902 patients with asbestos-related lung cancer, all identified as asbestos victims between 2009 and 2021. In both malignant mesothelioma and asbestos-related lung cancer, patients with occupational asbestos exposure exhibited not only shorter median survival times but also lower 3- and 5-year survival rates compared to those with environmental exposure. Additionally, a longer duration of occupational exposure and closer proximity to the source of asbestos were linked to shorter survival times and lower survival rates. Among the patients with occupational asbestos exposure, the highest hazard ratios (HRs) were observed in those who worked in the production of asbestos-containing products across both cancer types. In contrast, significant HRs were only noted in mesothelioma patients who lived near asbestos industries, slate houses, and redevelopment areas, within the environmentally exposed group. [ABSTRACT FROM AUTHOR]

BackgroundMalignant mesothelioma (MM) is a rare and aggressive tumor that is found in the pleura and peritoneum. A few cases of MM in the pericardium and tunica vaginalis testis have been reported. Moreover, primary occurrence in the atrium is extremely rare. The visual appearance of this tumor is similar to that of a common atrial myxoma, which makes it challenging for clinicians and radiologists to diagnose and treat this disease.Case demonstrationAn 18-year-old woman presented with symptoms of chest pain, shortness of breath, cough, and expectoration for 7 days. Echocardiography was performed on the patient, which revealed an atrial mass. Myxoma was one of the differential diagnoses. The tumor was an elliptical mass with tips, and the cut surface was jelly-like, similar to myxoma. After surgery, a pathologic examination of the biopsied tumor confirmed epithelial-type MM. During postoperative follow-up, no recurrence of the tumor was observed.ConclusionsMM originating in the atrium is considered to be extremely rare. Consequently, clinicians can easily misdiagnose atrial MM as a myxoma. Moreover, to confirm the diagnosis, histopathologic biopsy, histomorphological characterization, immunohistochemistry, and molecular genetic testing are required. Therefore, clinical diagnosis and treatment of MM are challenging.

Abstract Background Asbestos lung content is regarded as the most reliable tool for causal attribution of malignant mesothelioma (MM) to previous asbestos exposures. However, there is a lack of studies on asbestos burden in lungs of MM patients in comparison with healthy individuals. This study aims to provide such a comparison, investigating, as well, differences in asbestos lung burden with sex and time trends. Methods Asbestos lung content has been assessed on formalin-fixed lung fragments using scanning electron microscopy coupled with energy dispersion spectroscopy (SEM–EDS) on individuals deceased from MM (cases) and healthy subjects without any lung disease who died from violent causes (controls) between 2005 and 2023. Results Asbestos and asbestos bodies (ABs) were found, respectively, in 73.7% and 43.2% of cases and in 28 and 22% of controls; in MM cases the most represented asbestos types were crocidolite and amosite, whereas in controls it was tremolite-actinolite asbestos. The concentration of both asbestos fibers and ABs was statistically significantly higher in MM cases compared to controls. The mean asbestos fibers width was also significantly higher in cases than controls. Males and females with MM showed similar asbestos and ABs concentrations, but females had higher concentrations of chrysotile, and significantly lower fibers width compared to males. Time trends show that MM lung asbestos concentrations decreased starting in 2011. Discussion The results suggest a correlation between asbestos burden in lungs and MM risk. The different concentration of chrysotile, as well as the different width of asbestos fibers in MM males and females might reflect a sex difference in response of the lung microenvironment to inhaled asbestos. Finally, this study provides the first pathological evidence of the effect of the ban of asbestos use, demonstrating a significant decrease of asbestos lung content after 2011.

Asbestos exposure is associated with different asbestos-related diseases, including malignant mesothelioma (MM). MM diagnosis is confirmed with immunohistochemical analysis of several markers, including calretinin. Increased circulating calretinin was also observed in MM. The aim of the study was to determine if CALB2 polymorphisms or polymorphisms in genes that can regulate calretinin expression are associated with serum calretinin levels or MM susceptibility.

Malignant mesothelioma is a rare tumor associated with asbestos exposure. Mesothelioma carcinogenesis is related to enhanced reactive oxygen species (ROS) production and iron overload. Despite the recent advances in biomedical sciences, to date the only available treatments include surgery in a small fraction of patients and platinum-based chemotherapy in combination with pemetrexed. In this view, the purpose of this study was to evaluate the therapeutic potential of the newly synthetized platinum prodrug Pt(IV)Ac-POA compared to cisplatin (CDDP) on human biphasic mesothelioma cell line MSTO-211H using different complementary techniques, such as flow-cytometry, transmission electron microscopy (TEM), and immunocytochemistry. Healthy mesothelial cell lines Met-5A were also employed to assess the cytotoxicity of the above-mentioned compounds. Our in vitro results showed that Pt(IV)Ac-POA significantly interfere with iron metabolisms and more importantly is able to trigger cell death, through different pathways, including ferroptosis, necroptosis, and apoptosis, in neoplastic cells. On the other hand, CDDP triggers mainly apoptotic and necrotic cell death. In conclusion, Pt(IV)Ac-POA may represent a new promising pharmacological agent in the treatment of malignant mesothelioma.

Background: Asbestos lung content is regarded as the most reliable tool for causal attribution of malignant mesothelioma (MM) to previous asbestos exposures. However, there is a lack of studies on asbestos burden in lungs of MM patients in comparison with healthy individuals. This study aims to provide such a comparison, investigating, as well, differences in asbestos lung burden with sex and time trends. Methods: Asbestos lung content has been assessed on formalin-fixed lung fragments using scanning electron microscopy coupled with energy dispersion spectroscopy (SEM–EDS) on individuals deceased from MM (cases) and healthy subjects without any lung disease who died from violent causes (controls) between 2005 and 2023. Results: Asbestos and asbestos bodies (ABs) were found, respectively, in 73.7% and 43.2% of cases and in 28 and 22% of controls; in MM cases the most represented asbestos types were crocidolite and amosite, whereas in controls it was tremolite-actinolite asbestos. The concentration of both asbestos fibers and ABs was statistically significantly higher in MM cases compared to controls. The mean asbestos fibers width was also significantly higher in cases than controls. Males and females with MM showed similar asbestos and ABs concentrations, but females had higher concentrations of chrysotile, and significantly lower fibers width compared to males. Time trends show that MM lung asbestos concentrations decreased starting in 2011. Discussion: The results suggest a correlation between asbestos burden in lungs and MM risk. The different concentration of chrysotile, as well as the different width of asbestos fibers in MM males and females might reflect a sex difference in response of the lung microenvironment to inhaled asbestos. Finally, this study provides the first pathological evidence of the effect of the ban of asbestos use, demonstrating a significant decrease of asbestos lung content after 2011. [ABSTRACT FROM AUTHOR]

Ectopic decidua is a rare benign condition, believed to be associated with excessive progesterone stimulation such as in multiple gestations as in our case, it's usually asymptomatic and found incidentally during caesarean section. The lesions involute spontaneously in the postpartum period; therefore it usually doesn't require any therapeutic interventions. This condition could induce anxiety to surgeons intra-operatively, because of resemblance of more sinister lesions such as: carcinomatosis and granulomas. We report a clinical case of diffuse peritoneal deciduosis, identified during an emergency caesarean section, performed at 33 weeks of gestation, for a transverse lie, twins DCDA pregnancy in active labor. [ABSTRACT FROM AUTHOR]

Several attempts have been made to develop targeted therapies for malignant mesothelioma (MM), an aggressive tumour with a poor prognosis. In this study we evaluated whether Curcumin (CUR) potentiated the antitumor activity of the ErbB receptors inhibitor Afatinib (AFA) on MM, employing cell lines cultured in vitro and mice bearing intraperitoneally transplanted, syngeneic MM cells. The rationale behind this hypothesis was that CUR could counteract mechanisms of acquired resistance to AFA. We analysed CUR and AFA effects on MM cell growth, cell cycle, autophagy, and on the modulation of tumour-supporting signalling pathways. This study demonstrated that, as compared to the individual compounds, the combination of AFA + CUR had a stronger effect on MM progression which can be ascribed either to increased tumour cell growth inhibition or to an enhanced pro-apoptotic effect. These results warrant future studies aimed at further exploring the therapeutic potential of AFA + CUR-based combination regimens for MM treatment. [ABSTRACT FROM AUTHOR]

Background: The combination of immunobiological agents with immune checkpoint proteins is a promising treatment for malignant pleural mesothelioma (MPM). Mesothelin and anti-PD-L1 antibody-drug conjugates specifically target malignant neoplastic cells, inhibit the migration and invasion of neoplastic cells, and restore the immune landscape. In this study, we confirmed the importance of mesothelin and examined the relationship between mesothelin and the immune landscape of the tumor microenvironment (TME) in two MPM cohorts. Methods: The discovery cohort included 82 MPM cases. Tissue microarray slides were generated, and samples were processed for hematoxylin & eosin staining, immunohistochemistry, and immunofluorescence assays. The relationship between mesothelin, biomarkers of histogenesis, histological aggressiveness, PD-L1, immune cells (CD4, CD8, CD20, CD68), and collagen type I and type V fibers was evaluated by quantitative digital analyses. The outcome was the survival time until death from disease recurrence. The exploratory cohort included 87 malignant mesothelioma (MESO) patients from The Cancer Genome Atlas database. Results: Most patients were male (70.7%) with a history of asbestos exposure (53.7%) and with the epithelioid subtype (89%). Surgical resection was performed in 85.4% of patients, and 14.6% received chemotherapy; 59.8% of patients died from disease extension to the mediastinum. Low tumor mesothelin expression was associated with tumor necrosis and nuclear grade 1, whereas high mesothelin expression was significantly associated with the epithelioid histotype and high density of T cells CD8+, macrophages CD68+, and collagen type I fibers. Cox multivariate analysis showed a high risk of death for non-operated patients [hazard ratio (HR), 3.42 (1.15-10.16)] with low tumor mesothelin levels [HR, 2.58 (1.09-6.10)] and high PD-L1 and low infiltration of T cells CD4+ [HR, 3.81 (1.58-9.18)]. In the exploratory cohort, low mesothelin and high COL1A1 and COL5A1 expression were associated with poor overall survival. Conclusion: Tumor mesothelin expression associated with the TME immune landscape predicts the risk of death for patients with MPM and could be a new target for immunotherapy in MPM. [ABSTRACT FROM AUTHOR]

Objectives Pleural mesothelioma is a rapidly progressing pleural neoplasm caused by asbestos exposure of a long latency around 30-40 years. Patients with mesothelioma are usually diagnosed at a late stage with poor outcomes in terms of morbidity and mortality with 6–12 months' median survival. Despite the prohibited use of asbestos, malignant pleural mesothelioma is still increasingly being occurred in young age and female patients. Different un-standardized biomarkers have been used to diagnose MPM as mesothelin and febulin with controversial results, so we used CD 24 as a biomarker to diagnose and differentiate between different subtypes of malignant pleural mesothelioma. Materials and methods Our cohort study included total of fifty-nine patients with exudative pleural effusion. All patients underwent full history taking, clinical examination, blood tests (CBC, coagulation profile, liver and kidney functions), tapping of pleural effusion and to send pleural fluid investigations for LDH, albumin, total protein and albumin, then confirmed exudative pleural effusion patients were subjected to thoracic ultrasonography and medical thoracoscopy for the majority of cases or ultrasound guided biopsy in selected cases to obtain pleural biopsies for histopathology and then the examination of pleural biopsies for CD24 expression. Results Our study demonstrated the possibility of using CD24 as a biomarker in the immunostaining of pleural biopsies to differentiate between malignant pleural mesothelioma and pleural malignancy other than mesothelioma (18 mesothelioma cases versus 2 nonmesothelioma malignant cases) with high statistical significance P value < 0.001 and also it can discriminate between subtypes of mesothelioma as it showed marked significance in epithelioid subtype (12 epithelioid versus 1 sarcomatoid versus 5 biphasic subtypes) with more uptake by score +2 in epithelioid mesothelioma. Conclusions CD24 can be supposed to be a routine biomarker for immunohistochemistry of pleural tissue samples in diagnosis of mesothelioma and it can be used to differentiate between subtypes of malignant mesothelioma subtypes. [ABSTRACT FROM AUTHOR]

Malignant mesothelioma (MM) is a very aggressive neoplasia with a short life expectancy and limited therapeutic options. Thus, the identification of novel molecular targets is a matter of great urgency. Kelch-like (KLHL) proteins play an important role in a number of physiological and pathological cell-regulatory processes. Among this family, the function of KLHL14 is still very poorly characterized. KLHL14 was originally identified as a gene involved in regulating the epithelial-mesenchymal transition (EMT) process. Here, we demonstrate that KLHL14 not only prevents EMT but also plays an anti-oncogenic role in MM. Indeed, KLHL14 depletion enhanced proliferation, motility, invasion and colony formation in MM cells. Importantly, we also demonstrated that KLHL14 mechanism of action is dependent on Transforming Growth Factor β (TGF-β). In fact, TGF-β promotes de novo synthesis, increases protein stability and induces nuclear-cytoplasmic shuttling of KLHL14. Collectively, this research is an important step further to decipher KLHLs mechanism of action and further contributes to the understanding of the molecular mechanisms regulating MM.

Malignant mesothelioma of the testes is an aggressive, yet rare urogenital malignancy, accounting for an infinitesimally small number of oncologic diagnoses. This infrequent occurrence is accompanied by a relative lack of knowledge surrounding this disease, thus limiting management options beyond surgical intervention. Oftentimes, these malignancies present with a poor prognosis despite early intervention and only worsen in the event of metastatic spread with poor survival and limited response to treatment, if any. Our case documents positive patient outcomes following the use of aggressive surgical intervention in the management of a metastatic testicular mesothelioma. A healthy 80-year-old male with sudden painless testicular swelling requiring radical orchidectomy following failed initial conservative management. Pathologically, the specimen was diagnosed as malignant mesothelioma of the right testis with involvement of the tunica albuginea and tunica vaginalis. Following disease recurrence at 82 years of age, the patient subsequently opted for an open right-sided template non-nerve sparing retroperitoneal lymph node dissection which was undertaken without complication. Malignant mesothelioma of the testes remains an ominous diagnosis with historically poor outcomes and for which surgical intervention remains the mainstay of treatment. The retroperitoneal lymphatic drainage represents the most common route of metastatic spread for testicular tumours; however, retroperitoneal lymph node dissection has rarely been employed in this patient population and never in an individual of this age. Our findings contribute to the growing literature surrounding these rare malignancies and outline the importance of considering both patient autonomy and the clinical picture in disease management.

Objective To investigate the expression of peptidylarginine deiminase 2 and 4 (PAD2 and PAD4) in malignant mesothelioma (MM), their correlation with citrullinated proteins and clinical significance. Methods The pathological samples of 45 cases of MM in Zhejiang province from 2014 to 2021 were collected retrospectively for constructing paraffin-embedded tissue microarray. The expressions of PAD2 and PAD4 in tumor and paired adjacent tissues were detected by immunohistochemistry and the clinical significance was analyzed by utilizing bioinformatics database. Results The expressions of PAD2 and PAD4 in MM tissues were significantly higher than those in adjacent tissues (P