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Abstract The combination of cisplatin and pemetrexed remains the gold standard chemotherapy for malignant pleural mesothelioma (MPM), although resistance and poor response pose a significant challenge. Cytidine deaminase (CDA) is a key enzyme in the nucleotide salvage pathway and is involved in the adaptive stress response to chemotherapy. The cytidine analog capecitabine and its metabolite 5′-deoxy-5-fluorocytidine (5’-DFCR) are converted via CDA to 5-fluorouracil, which affects DNA and RNA metabolism. This study investigated a schedule-dependent treatment strategy, proposing that initial chemotherapy induces CDA expression, sensitizing cells to subsequent capecitabine treatment. Basal CDA protein expression was low in different mesothelioma cell lines but increased in the corresponding xenografts. Standard chemotherapy increased CDA protein levels in MPM cells in vitro and in vivo in a schedule-dependent manner. This was associated with epithelial-to-mesenchymal transition and with HIF-1alpha expression at the transcriptional level. In addition, pretreatment with cisplatin and pemetrexed in combination sensitized MPM xenografts to capecitabine. Analysis of a tissue microarray (TMA) consisting of samples from 98 human MPM patients revealed that most human MPM samples had negative CDA expression. While survival curves based on CDA expression in matched samples clearly separated, significance was not reached due to the limited sample size. In non-matched samples, CDA expression before but not after neoadjuvant therapy was significantly associated with worse overall survival. In conclusion, chemotherapy increases CDA expression in xenografts, which is consistent with our in vitro results in MPM and lung cancer. A subset of matched patient samples showed increased CDA expression after therapy, suggesting that a schedule-dependent treatment strategy based on chemotherapy and capecitabine may benefit a selected MPM patient population.

Abstract The clinical impact of soluble molecules in pleural effusion (PE) is unclear in patients with malignant pleural mesothelioma (MPM). In this single-center, retrospective, observational study, we assessed soluble forms of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), and PD-1 ligand 1 (PD-L1) using enzyme-linked immunosorbent assays; three TGF-β isoforms were measured via multiplex assay in PE of patients with fibrinous pleuritis (FP) or MPM, to assess relationships between the levels of six molecules, clinicopathological characteristics, and efficacy of immune checkpoint inhibitors. Soluble forms of CTLA-4, PD-L1, PD-1, TGF-β1, TGF-β2, and TGF-β3 were variably produced in PE of FP (n = 34) and MPM (n = 79); we found significant relationships between the six molecules and clinicopathological features. Although none of the three soluble immune checkpoint molecules showed diagnostic or prognostic effects in patients with MPM, TGF-β2 level in PE is a useful differential diagnostic marker between FP and MPM. Both TGF-β1 and TGF-β3 levels are promising prognostic markers for MPM. Moreover, we found that higher baseline levels of PD-1 soluble forms predicted the response to anti-PD1 monotherapy. Our findings identify novel diagnostic, prognostic, and predictive biomarkers for anti-PD1 therapy in patients with MPM.

Abstract With cancer immunotherapy and precision medicine dynamically evolving, there is greater need for pre-clinical models that can better replicate the intact tumor and its complex tumor microenvironment (TME). Precision-cut tumor slices (PCTS) have recently emerged as an ex vivo human tumor model, offering the opportunity to study individual patient responses to targeted therapies, including immunotherapies. However, little is known about the physiologic status of PCTS and how culture conditions alter gene expression. In this study, we generated PCTS from head and neck cancers (HNC) and mesothelioma tumors (Meso) and undertook transcriptomic analyses to understand the changes that occur in the timeframe between PCTS generation and up to 72 h (hrs) in culture. Our findings showed major changes occurring during the first 24 h culture period of PCTS, involving genes related to wound healing, extracellular matrix, hypoxia, and IFNγ-dependent pathways in both tumor types, as well as tumor-specific changes. Collectively, our data provides an insight into PCTS physiology, which should be taken into consideration when designing PCTS studies, especially in the context of immunology and immunotherapy.

Abstract Long noncoding RNAs have been shown to be involved in a myriad of physiological and pathological pathways. To date, malignant pleural mesothelioma (MPM) is considered an extremely aggressive cancer. One reason for this is the late diagnosis of the disease, which can occur within 30–40 years of asbestos exposure. There is an immense need for the development of new, sensitive, inexpensive and easy methods for the early detection of this disease other than invasive methods such as biopsy. The aim of this study was to determine the expression of circulating lncRNAs in mesothelioma patient plasma to identify potential biomarkers. Ten previously identified lncRNAs that were shown to be aberrantly expressed in mesothelioma tissues were selected as candidates for subsequent validation. The expression of the ten selected candidate lncRNAs was verified via quantitative PCR (qPCR) in human plasma samples from mesothelioma patients versus healthy controls. The expression levels of circulating GAS5, SNHG8 and MALAT1 were significantly greater in plasma samples from patients than in those from controls. The ROC analysis of both MALAT1 and SNHG8 revealed 88.89% sensitivity and 66.67% specificity. The sensitivity of these markers was greater than that of GAS5 (sensitivity 72.22% and specificity 66.67%). The regression model for GAS5 was statistically significant, while that for SNHG8 and MALAT1 was not significant due to the small sample size. The area under the curve (AUC) of the three ROC curves was acceptable and significant: 0.7519 for GAS5, 0.7352 for SNHG8 and 0.7185 for MALAT1. This finding confirmed their ability to be used as markers. The three lncRNAs were not affected by age, sex or smoking status. The three lncRNAs showed great potential as independent predictive diagnostic biomarkers. Although the prediction model for MALAT1 did not significantly differ, MALAT1 was significantly expressed in patients more than in controls (p = 0.0266), and the recorded sensitivity and specificity were greater than those of GAS5.

Abstract Background Testicular tumors have many different manifestations. The majority of these cases are presented as an incidental finding during hydrocelectomy. Malignant mesotheliomas are uncommon tumours that can arise from the coelomic epithelium of the pleura, peritoneum, pericardium, and tunica vaginalis. Case presentation We present a 51-year-old South Asian (Indian) male patient with a rare case of mesothelioma, presenting with right hydrocele, to whom a right hydrocelectomy was performed. Any history of trauma or asbestos exposure was not present. Histopathological and immunohistochemistry reports revealed a malignant mesothelioma of tunica vaginalis. There was no invasion of the tumour to the epididymis and spermatic cord. Imaging studies showed no signs of metastasis. 1 month later, a high inguinal orchidectomy was performed. The patient underwent adjuvant chemotherapy thereafter and is still on follow-up. Conclusion Although hydrocele is common, detailed evaluation is mandatory to rule out certain rare tumours-testicular and paratesticular variants.

Mesothelioma is a locally aggressive malignant tumor that arises on the mesothelial surfaces of the pleura, peritoneum and tunica vaginalis. There are three histologic subtypes of mesothelioma: epithelioid, biphasic, and sarcomatoid. Pleural mesothelioma is usually characterized by diffuse pleural thickening. Disease progression is characterized by local invasion of the chest wall and lung. Lymphatic metastasis is rare and hematogenous metastasis is much rarer. The purpose of these case reports is to emphasize that pleural mesothelioma metastases can occur in unexpected places and to contribute to the literature.

The pathologic diagnosis of pleural mesothelioma is generally based on international guidelines, but no compulsory points based on different drugs approvals in different European countries are required to be reported. According to the last (2021) edition of the World Health Organization classification of pleural tumors, the nuclear grade of epithelioid-type mesothelioma should be always inserted in the pathologic report, while the presence of BRCA-associated protein-1 (BAP1) (clone C4) loss and a statement on the presence of the sarcomatoid/nonepithelioid component are fundamental for both a screening of patients with suspected BAP1 tumor predisposition syndrome and the eligibility to perform first-line immunotherapy at least in some countries. Several Italian experts on pleural mesothelioma who are deeply involved in national scientific societies or dedicated working groups supported by patient associations agreed that the pathology report of mesothelioma of the pleura should always include the nuclear grade in the epithelioid histology, which is an overt statement on the presence of sarcomatoid components (at least 1%, in agreement with the last classification of pleural mesothelioma) and the presence of BAP1 loss (BAP1-deficient mesothelioma) or not (BAP1-retained mesothelioma) in order to screen patients possibly harboring BAP1 tumor predisposition syndrome. This review aims to summarize the most recent data on these three important elements to provide evidence regarding the possible precision needs for mesothelioma.

The association of mesothelioma, a lethal lung disease, with asbestos has led to an absolute ban on asbestos in at least 55 countries worldwide. The purpose of this paper is to review residual exposure to asbestos as well as other emerging causes of mesothelioma outside asbestos. The review provides detailed description of asbestos minerals, their geographical locations, mesothelioma in these areas, as well as contemporary possible sources of asbestos exposure. Second, we examine other emerging causes of mesothelioma including: ionizing radiation as the second most important risk factor after asbestos, particularly relevant to patients undergoing radiotherapy, third, carbon nanotubes which are under investigation and fourth, Simian virus 40. In the case of asbestos per se, the greatest risk is from occupational exposure during mining and subsequent processing. Of the non-occupational exposures, environmental exposure is most serious, followed by exposure from indoor asbestos minerals and secondary familial exposure. Overall, asbestos is still a major risk factor, but alternative causes should not be neglected, especially in young people, in women and those with a history of radiotherapy or living in high-risk locations.

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) gives encouraging results in the treatment of peritoneal metastasis (PM). The current recommendations require at least 3 sessions of PIPAC. However, some patients do not complete the full treatment course and stop after only 1 or 2 procedures, hence the limited benefit. A literature review was performed, with search terms including “PIPAC” and “pressurised intraperitoneal aerosol chemotherapy.”

Plain English summary Patient and public involvement (PPI) in research means research that is done ‘with’ or ‘by’ the public, not ‘to’, ‘about’, or ‘for’ them. Involving patients, family caregivers or the public (e.g. coordinators of patient organisations) in research activities means that they contribute to how research is designed, conducted, or disseminated. However, some diseases where patients have a short prognosis after diagnosis make it harder for patients or their family members to get involved. In this project we explored the perspectives of patients, public, and researchers on how PPI could be increased and maintained in research on mesothelioma—a rare cancer of the lining of the lung or of the peritoneum caused by exposure to asbestos. We conducted an online survey with mesothelioma researchers, and they indicated a number of PPI benefits but also challenges such as finding people living with mesothelioma well enough to participate. We also conducted six online workshops and thirteen interviews with patients, family members and coordinators of mesothelioma patient organisations—these were not PPI representatives but participants in research. All participants in the project were motivated by the wish to enhance outcomes for other patients. Their understanding of PPI improved during the project and they saw a number of challenges to others becoming involved in PPI, such as its abstract nature and the use of scientific language. We recommend that researchers engage long-term with mesothelioma support groups so that they have opportunities to explain what PPI means and involve people affected by mesothelioma in research.

Benign multicystic peritoneal mesothelioma (BMPM) is a rare neoplasm that is difficult to distinguish from other cystic neoplasms radiologically. A 41-year-old female patient was admitted to the emergency service with a complaint of abdominal pain. After the physical examination, and radiological imaging, ovarian torsion was assumed, and a gynecological laparoscopy was planned. A firm mass was observed in the cecal region during gynecological laparoscopy, and a right hemicolectomy was performed. There was a multicystic mass measuring 4x4x2.5 cm in the cecal region of the specimen is sent to the pathology department. Morphological findings on hematoxylin-eosin sections and immunohistochemical studies supported it, and a diagnosis of BMPM was made. The diagnosis of BMPM, which can be a challenging process considering its clinical and radiological features, is mainly made pathologically. These lesions frequently recur and rarely show a malignant transformation. Therefore, it must be evaluated in the pathological differential diagnosis.

A 40-year-old male patient presented with an unexplained pericardial effusion and was treated with antituberculosis therapy. This patient showed a transient improvement, but then progressively worsened to develop constrictive pericarditis, multiple plasma chamber effusions, and venous thrombosis. The patient was transferred to Zhongshan Hospital, Fudan University. Through a pleural histopathological biopsy, this patient was diagnosed with pleural mesothelioma and secondary malignant tumor of the pericardium. Later, clinical the manifestations of patient progressed rapidly, resulting in the death of the patient. Mesothelioma is a very rare group of malignant tumors originating from the pleura and other tissues. Patients are mostly advanced at the time of initial diagnosis, with limited treatments and short median survival. It is important to strengthen the understanding of mesothelioma, pay attention to all medical and technical examinations, especially dynamic follow-up of changes in the disease for early diagnosis of this disease.

Pleural mesothelioma (PM) is a type of cancer that is highly related to exposure to asbestos fibers. It shows aggressive behavior, and the current therapeutic approaches are usually insufficient to change the poor prognosis. Moreover, apart from staging and histological classification, there are no validated predictors of its response to treatment or its long-term outcomes. Numerous studies have investigated minimally invasive biomarkers in pleural fluid or blood to aid in earlier diagnosis and prognostic assessment of PM. The most studied marker in pleural effusion is mesothelin, which exhibits good specificity but low sensitivity, especially for non-epithelioid PM. Other biomarkers found in pleural fluid include fibulin-3, hyaluronan, microRNAs, and CYFRA-21.1, which have lower diagnostic capabilities but provide prognostic information and have potential roles as therapeutic targets. Serum is the most investigated matrix for biomarkers of PM. Several serum biomarkers in PM have been studied, with mesothelin, osteopontin, and fibulin-3 being the most often tested. A soluble mesothelin-related peptide (SMRP) is the only FDA-approved biomarker in patients with suspected mesothelioma. With different serum and pleural fluid cut-offs, it provides useful information on the diagnosis, prognosis, follow-up, and response to therapy in epithelioid PM. Panels combining different markers and proteomics technologies show promise in terms of improving clinical performance in the diagnosis and monitoring of mesothelioma patients. However, there is still no evidence that early detection can improve the treatment outcomes of PM patients.

Abstract Background Splenosis is the heterotopic autotransplantation of splenic tissue after severe splenic trauma and/or splenectomy. The epidemiology is elusive, but splenosis is frequently misdiagnosed as malignant tumors of gastrointestinal, gynecological, or hematological origin before the correct diagnosis is ultimately found. We herein report a rare case of combined, extensive intraabdominal and intrathoracic splenosis initially presenting as pleural mesothelioma. Case presentation A 63-year-old Caucasian male presented with dyspnea and recurring thoracic pain. Initial X-ray and computed tomography scans showed disseminated intrathoracic and intraabdominal lesions. Consequently, thoracoabdominal mesothelioma or a polytopically metastasized cancer of unknown origin was suspected. A thorough examination of the patient’s medical history and contrast-enhanced ultrasound by a skilled examiner revealed the diagnosis of extensive abdominal and thoracic splenosis as a consequence of an abdominal gunshot wound with a ruptured diaphragm several decades earlier. Timely diagnosis by noninvasive measures prevented the patient from potential complications of harmful diagnostic procedures, including nuclear imaging and biopsies. The patient is currently treated for hepatitis C and chronic obstructive lung disease, whereas no specific treatment for splenosis is required. Conclusions We present a case of rare intrathoracic and intraperitoneal splenosis mimicking mesothelioma. Contrast-enhanced ultrasound and thorough patient history were used for diagnosis and prevented this patient from having to undergo potentially harmful diagnostics. Splenosis can occur after splenic trauma and, consequently, needs to be considered as a rare differential diagnosis to malignant tumors of various origins when a matching patient history is obtained.

The transcription factor TEAD, together with its coactivator YAP/TAZ, is a key transcriptional modulator of the Hippo pathway. Activation of TEAD transcription by YAP has been implicated in a number of malignancies, and this complex represents a promising target for drug discovery. However, both YAP and its extensive binding interfaces to TEAD have been difficult to address using small molecules, mainly due to a lack of druggable pockets. TEAD is post-translationally modified by palmitoylation that targets a conserved cysteine at a central pocket, which provides an opportunity to develop cysteine-directed covalent small molecules for TEAD inhibition. Here, we employed covalent fragment screening approach followed by structure-based design to develop an irreversible TEAD inhibitor MYF-03–69. Using a range of in vitro and cell-based assays we demonstrated that through a covalent binding with TEAD palmitate pocket, MYF-03–69 disrupts YAP-TEAD association, suppresses TEAD transcriptional activity and inhibits cell growth of Hippo signaling defective malignant pleural mesothelioma (MPM). Further, a cell viability screening with a panel of 903 cancer cell lines indicated a high correlation between TEAD-YAP dependency and the sensitivity to MYF-03–69. Transcription profiling identified the upregulation of proapoptotic BMF gene in cancer cells that are sensitive to TEAD inhibition. Further optimization of MYF-03–69 led to an in vivo compatible compound MYF-03–176, which shows strong antitumor efficacy in MPM mouse xenograft model via oral administration. Taken together, we disclosed a story of the development of covalent TEAD inhibitors and its high therapeutic potential for clinic treatment for the cancers that are driven by TEAD-YAP alteration.

Introduction The prognosis of malignant pleural mesothelioma (MPM) is poor, with a limited survival time. In this study, we aimed to examine expression levels of genes selected from relevant literature and to utilize in silico methods to determine genes whose expression could reflect the prognosis of patients with MPM by ex-vivo validation experiments. Material and methods The study group consisted of 54 MPM patients treated with chemotherapy. Expression of 6 genes – midkine (MDK), syndecan-1 (SDC1), hyaluronan synthase-2 (HAS2), sestrin-1 (SESN1), laminin subunit alpha-4 (LAMA4), and fibulin-3 (FBLN3) – was examined by qPCR in tumor tissues. Sestrin-1 and LAMA4 were identified using an in house R-based script: Unsupervised Survival Analysis Tool. Midkine, SDC1, HAS2, and FBLN3 were selected from current literature. We used two housekeeping genes, i.e. glucose-6-phosphate dehydrogenase and TATA-box binding protein, as controls. Results Of the patients, 43 (79.6%) had epithelioid mesothelioma. The median survival for all patients was 10 (±1.2 SE) months (95% CI: 7.7–12.3). In multivariate analyses, MDK (p = 0.007), HAS2 (p = 0.008) and SESN1 (p = 0.014) expression levels were related to survival time in the whole group. In epithelioid type MPM patients, MDK (p = 0.014), FBLN3 (p = 0.029), HAS2 (p = 0.014) and SESN1 (p = 0.045) expression was related to survival time in multivariate analyses. Conclusions High HAS2 and SESN1 expressions and low MDK are potential biomarkers of good prognosis in MPM. High HAS2 and SESN1 expression and low MDK and FBLN3 can also be utilized as biomarkers of good prognosis for epithelioid MPM. Those results should be further investigated in sera, plasma, and pleural effusions.

Introduction There is no consensus about the standardized uptake value maximum (SUV max ) cut-off value to characterize pleural thickening worldwide. Sometimes, this causes unnecessary invasive diagnostic procedures. Our first aim is to determine a cut-off value for SUV max . Secondly, we try to answer the following question: If we use this cut-off value together with morphological parameters, can we differentiate benign thickening from malignant pleural mesothelioma (MPM) more accurately? Material and methods Thirty-seven patients who underwent 2-deoxy-2-fluoro-D-glucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) before pleural biopsy were included the study. All of patients had histopathologically proven primary pleural disease. Their [18F]FDG-PET/CT imaging reports were re-assessed. If a patient’s SUVmax or size of the thickening was not mentioned in the report, we calculated it with their [18F]FDG-PET/CT. Results Age, pleural effusion, size, and SUV max were found to have a relationship with MPM. We found the size > 14 mm, and SUV max > 4.0 as cut-off values for MPM. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for size > 14 mm were found to be 86.4%, 85.2%, 82.6%, 88.5%, respectively. For SUV max > 4.0, sensitivity, specificity, PPV, NPV were 90.9%, 87.0%, 85.1%, 92.2%, respectively. Conclusions If a patient has SUV max > 4.0 and/or size > 14 mm, the risk of MPM is high. These patients should undergo biopsy. If a patient’s SUV max < 4.0, size < 14 mm and does not have pleural effusion, he/she has low risk for MPM. These patients can undergo the follow-up. If a patient’s SUV max < 4, size < 14, and has pleural effusion the MPM risk is approximately 4%. These patients can undergo biopsy/cytology/follow-up. Novel studies are needed for these patients.

Asbestos is a mineral known as human carcinogenic material. Exposure to asbestos both in an occupational and environmental way causes asbestosis and mesothelioma. ROS contributes to the development of pulmonary-toxicity induced asbestos.We aimed to determine the levels of important mitochondrial substances such as manganese superoxide dismutase (MnSOD) and Thioredoxin (Trx2) in asbestosis and mesothelioma patients. The study was performed with the patients admitted to outpatient clinics of Chest Diseases and Thoracic Surgery, at Medicine Faculty, Bozok University. Group 1 (healthy control group, n=27): Consisting of healthy individuals (54.18±9.89 years old), Group 2 (patients group, n=34): Evaluation of clinical, pathological and radiological analysis, patients who defined as mesothelioma and/or pleural plaques and asbestosis (60.24±15.24 years old). Patients, who were not biopsied or not available for biopsy due to comorbid diseases, were not included in the study.Biochemical analysis was done in Selcuk University Medicine Faculty Research Laboratories.Serum Trx2 and MnSOD levels were determined by the Elisa method. The results of Trx2 were calculated as pg/µg protein. MnSOD samples were determined as ng/µg protein. MnSOD and Trx2 levels in the patients group were statistically lower than the levels of the healthy group (p=0.000, p=0.048), respectively.Trx2 levels were 1.74±0.33 pg/µg protein in a healthy group whereas were 0.89±0.10 pg/µg protein in asbestosis and mesothelioma group. Serum MnSOD levels were 1.38±0.24 and 0.29±0.11 ng/µg protein in healthy and patients groups, respectively.These significant changes in malignant mesothelioma patients reflect the impairment of the oxidant-antioxidant balance system. The study presents basic findings for the clinical meaning of mentioned biochemical parameters in mesothelioma patients. [Med-Science 2020; 9(4.000): 912-6]

Abstract Mesothelioma is a rare tumor usually located on the pleura. In this typical location, it is closely linked to asbestos exposure. However, in other locations such as in peritoneal mesothelioma, the association to asbestos remains unusual.

Background: The use of conventional flexible forceps during flex-rigid pleuroscopy can be challenging when sampling hard and thickened pleura. Pleuroscopic cryobiopsy is an emerging field, with various early studies demonstrating good yield and minimal complications. Objectives: To review the authors’ early experience of pleuroscopic cryobiopsy in their centre and highlight its utility in the diagnosis of mesothelioma. Method: Six cases of undiagnosed pleural effusion that underwent pleuroscopic cryobiopsy via flexi-rigid pleuroscopy between July 2017 and June 2019 were retrospectively analysed. Results: The cohort had a median age of 59 years, consisting of two females and four males with a median age of 57 years. Mean (aggregate) tissue sample diameter was 9.2±1.9 mm. Cryobiopsy established a definitive diagnosis in all six cases: one case of malignant mesothelioma, one pleural tuberculosis, two small cell carcinomas, and two adenocarcinomas. Immunohistochemical staining was performed in all five of the malignant samples (100%). There were no major complications reported. Conclusions: Based on the case series, pleuroscopic cryobiopsy is a feasible adjunct to conventional forceps biopsy, a safe procedure in the authors’ setting, gives high diagnostic yield, and enables differentiation between the different causes of exudative pleural effusion. A large, prospective study is required to validate this retrospective series.

Abstract Objective There is substantial evidence that exercise can safely reduce the risk of cancer and improve survival in different human cancer populations. Long latency periods associated with carcinogen–induced cancers like asbestos induced mesothelioma provide an opportunity to implement exercise as an intervention to delay or prevent disease development. However, there are limited studies investigating the ability of exercise to prevent or delay cancer, and exercise as a preventive strategy has never been assessed in models with a known carcinogen. We investigated the potential of voluntary exercise (VE) to delay development of asbestos related disease (ARD) in our well-characterised, asbestos induced MexTAg model of mesothelioma. Results Asbestos exposed MexTAg mice were given continuous or delayed access to VE and ARD assessed over time. We found that the addition of VE did not affect ARD development in asbestos exposed MexTAg mice. However, non–asbestos exposed, aged matched control mice participated in significantly more VE behaviours, suggesting subclinical development of ARD after asbestos exposure had a greater impact on VE participation than age alone. These data highlight the importance of model choice and the potential limitation that some pre–clinical studies may not accurately represent the clinical paradigm, particularly in the context of prevention studies.

Molecular next gene sequencing was used to evaluate mutations in 409 common mutated cancer-related genes in malignant mesothelioma of tunica vaginalis testis (MMTVT) of 81-year-old man. Multifocal papillary-solid areas contained necrosis among highly cellular fields with multiple mitoses. It was positive for WT1, CKAE1/AE3, calretinin, CK7 with negativity for CK5, PSA, TTF-1. Following mutations were revealed in PARP1 (NM_001618: c.2285TG, p.I49M) and two sorts of mutations in structure of KMT2C gene (NM_170606: c.2447_2448insA (c.2447dupA), p.Y816fs and NM_170606: c.1042G>A, p.D348N) for the first time in MMTVT.

A male patient presented with a signs and symptoms of a respiratory tract infection associated with a pleural effusion. The effusion had negative cytological analysis and a CT scan showed mild pleural thickening. The effusion resolved completely on chest radiographs and the patient was discharged from the respiratory service, but the effusion recurred. After further investigations and elucidating significant asbestos exposure in the medical history, mesothelioma was eventually diagnosed. The patient is currently receiving chemotherapy with palliative intent. This paper highlights the importance of ongoing follow-up in a patient with a label of benign asbestos-related pleural effusion.

A differential diagnosis of ascites is always challenging for physicians. Peritoneal tuberculosis is particularly difficult to distinguish from peritoneal carcinomatosis because of the similarities in clinical manifestations and laboratory results. Although the definitive diagnostic method for ascites is to take a biopsy of the involved tissues through laparoscopy or laparotomy, there are many limitations in performing biopsies in clinical practice. For this reason, physicians have attempted to find surrogate markers that can substitute for a biopsy as a confirmative diagnostic method for ascites. CA 125, which is known as a tumor marker for gynecological malignancies, has been reported to be a biochemical indicator for peritoneal tuberculosis. On the other hand, the sensitivity of serum CA 125 is low, and CA 125 may be elevated due to other benign or malignant conditions. This paper reports the case of a 66-year-old male who had a moderate amount of ascites and complained of dyspepsia and a febrile sensation. His abdominal CT scans revealed a conglomerated mass, diffuse omental infiltration, and peritoneal wall thickening. Initially, peritoneal tuberculosis was suspected due to the clinical symptoms, CT findings, and high serum CA 125 levels, but non-specific malignant cells were detected on cytology of the ascitic fluid. Finally, he was diagnosed with primary malignant peritoneal mesothelioma after undergoing a laparoscopic biopsy.

Abstract Nonislet tumor hypoglycemia (NICTH) is a rare paraneoplastic syndrome characterized by refractory hypoglycemia, which often requires multifaceted therapy. We reported a case of a patient with pleural malignant mesothelioma and developed NICTH, for which chemotherapy, glucocorticoids, and nutrition were given to achieve optimal glycemic control.

Benign multicystic peritoneal mesothelioma (BMPM) is a rare peritoneal tumor diagnosed predominantly in pre-menopausal women. Associated risk factors include endometriosis and pelvic inflammatory disease in women, and prior abdominal surgery in both genders. To date, the pathogenesis of this disease remains controversial with possible etiologies, including a neoplastic versus a reactive process. Given the risk factors, some authors believe that this disease is secondary to a reactive process. However, because some studies describe cases where there is no prior surgical history or inflammatory milieu present, and because of this entity’s predilection for recurrence, some authors believe the origin to be neoplastic. Some genetic and familial associations have also been reported. Malignant transformation is extremely rare, with only two cases reported in the literature, despite the recurrence potential. Like the etiology, the name of this entity is also controversial. Some authors prefer the term “peritoneal inclusion cyst (PCM)” instead of “benign cystic mesothelioma” and argue that the term mesothelioma should only be used when there is evidence of atypia. Most cases of BMPM are discovered incidentally. Others reflect sequela of tumor mass effect. It appears intra-operatively as large, multi-focal, cystic lesions in the peritoneal and pelvic cavity. Diagnosis is achieved through surgical sampling with histopathological examination. Immunobiologically, BMPM exhibits multiple small cystic spaces with flattened lining containing calretinin positive cells without atypical features, mitotic figures, or tissue invasion. Treatment includes cytoreductive surgery. Here we present a case of BMPM in a 60-year-old male – a rare disease in an uncommon patient population.

Objective: Malignant pleural mesothelioma (MPM) is a rare and aggressive malignant cancer for which there are poor treatment options. Extrapleural pneumonectomy (EPP) and pleurectomy decortication (P/D) are the two most used surgical procedures in patients with resectable disease. We reviewed the available literature in order to compare the overall survival and postoperative complications of EPP and P/D and to provide evidence for the best procedure in the treatment of MPM. Methods: We performed a systematic review of the literature, including studies from August 2018 to May 2022. The primary outcome was 5-year overall survival (OS) and the secondary outcomes were 30-day mortality, 90-day mortality and peri-operative complications. Results: Thirteen studies were considered, including a total of 1624 patients treated with EPP and 2147 treated with P/D. The estimated pooled HR showed a significant lower hazard for P/D compared to EPP in terms of OS (HR = 0.76; 95% CI from 0.62 to 0.94; p < 0.001). In 12 studies, the risk for 30-day mortality was lower for patients treated with P/D (RR = 0.49; 95% CI from 0.31 to 0.76; p = p = 0.10). The OS restricted mean survival time difference meta-analysis (RMSDT) confirms the superior survival of P/D on the EPP, a superiority that increases from 0.54 months at one year to 4.23 at five years. The incidence of postoperative empyema, atrial fibrillation, bleeding and bronchopleural fistula was significantly increased in the EPP group except for prolonged air leakage, which is only characteristic of P/D. Conclusions: Using two different statistical methods, this meta-analysis suggests that long-term survival after surgical treatment for resectable MPM is greater for patients undergoing P/D. Long-term survival had never been previously analyzed with appropriate tests; on the contrary, our result is consistent with the previous meta-analyses and reinforces the evidence of lower 30-day mortality and the prevalence of postoperative complications in P/D versus EPP patients. The recent introduction of innovative therapeutic schemes, both adjuvant and neoadjuvant therapy, keeps the discussion on surgical strategy open and will require new studies.

Objectives: We examined a series of malignant pleural mesothelioma (MPM) patients who consecutively underwent surgery in our institution during the last 20 years. Across this period, we changed our surgical approach to MPM, adopting extended pleurectomy and decortication (eP/D) instead of extrapleural pneumonectomy (EPP). In this study, we compare the perioperative outcomes and long-term survival of patients who underwent EPP vs. eP/D. Methods: A retrospective analysis was carried out of all the MPM patients identified from our departmental database who underwent EPP or P/D from 2000 to 2021. Clavien–Dindo criteria was adopted to score postoperative complications, while Kaplan–Meier methods and a Cox multivariable analysis were used to perform the survival analysis. Results: Of 163 patients, 78 (48%) underwent EPP and 85 (52%) eP/D. Induction chemotherapy was significantly administrated more often in the eP/D group (88% vs. 51%). Complete trimodality treatment including induction chemotherapy, radical surgery, and adjuvant radiotherapy was administered in 74% of the eP/D group versus 32% of the EPP group (p < 0.001). The postoperative morbidity rate was higher in the eP/D group (54%) compared to the EPP group (36%) (p = 0.02); no statistically significant differences were identified concerning major complications (EPP 43% vs. eP/D 24%, p = 0.08). No statistical differences were identified in 30-day mortality, 90-day mortality, median disease-free, and overall survival statistics between the two groups. The Cox multivariable analysis confirmed no induction chemotherapy (HR, 0.5; p = 0.002), RDW (HR, 1.08; p = 0.02), and the presence of pathological nodal disease (HR, 1.99; p = 0.001) as factors associated with worse survival in the entire series. Conclusions: Our data support that eP/D is a well-tolerated procedure allowing the implementation of a trimodality strategy (induction chemotherapy, surgery, and radiotherapy) in most MPM patients. When eP/D is offered in this setting, the oncological results are comparable to EPP. To obtain the best oncological results, the goal of surgical resection should be macroscopic complete resection (R0) in carefully selected patients (clinical N0).

Objective: Malignant Pleural Mesothelioma (MPM) has a poor prognosis and high symptom burden. RESPECT-Meso was a multicenter randomized study examining the role of early specialist palliative care (SPC) on quality of life (QoL) with MPM. This is a post-hoc exploratory analysis of the symptom burden and unmet needs identified from RESPECT-Meso participants. Methods: Exploratory analysis from 174 participants using the General Health Status (GHS) measure (from the EORTC QLQ-C30 QoL questionnaire) and 87 participants using validated assessment questionnaires in those randomized to SPC. Eligibility for the study included confirmed MPM with diagnosis <6 weeks prior, performance score (PS) 0 or 1, no significant physical or psychological comorbidity. Cox proportional hazards models were derived to examine for relationships with survival. Free text was assessed using content analysis, looking for common themes and words. Results: Participants were predominantly male (79.9%), mean age 72.8 years, PS was 0 in 38%, 78% of MPM was epithelioid. At least 3 symptoms were reported in 69.8% of participants, including fatigue (81%), dyspnea (73.3%), pain (61.2%), weight loss (59.3%). Anxiety was reported by 54.7% of participants, 52.3% low mood and 48.8% anhedonia symptoms. After multivariable adjustment, only pain remained statistically significant with a hazard ratio (HR) 2.9 (95% CI 1.3-6.7; p = 0.01). For each 1 unit increase in GHS score, the HR for death was 0.987 (0.978-0.996; p = 0.006), indicating a worse reported QoL is related to shorter survival. Unmet needs were common: 25.9% wanted more information about their condition, 24.7% about their care and 21.2% about their treatment. 79.1% were concerned about the effect of their illness on family. Conclusion: There is a high symptom burden in mesothelioma despite good baseline performance status. A worse QoL is associated with a worse survival. Unmet needs are common, perhaps highlighting a need for improved communication and information sharing. [ABSTRACT FROM AUTHOR]

Abstract Objective Malignant mesothelioma is an aggressive cancer of the serous membranes. For the detection of the tumor at early stages non- or minimally-invasive biomarkers are needed. The circulating biomarkers miR-132-3p, miR-126-3p, and miR-103a-3p were analyzed in a nested case–control study using plasma samples from 17 prediagnostic mesothelioma cases and 34 matched asbestos-exposed controls without a malignant disease. Results Using prediagnostic plasma samples collected in median 8.9 months prior the clinical diagnosis miR-132-3p, miR-126-3p, and miR-103a-3p revealed 0% sensitivity on a defined specificity of 98%. Thus, the analyzed miRNAs failed to detect the cancer in prediagnostic samples, showing that they are not feasible for the early detection of malignant mesothelioma. However, the miRNAs might still serve as possible markers for prognosis and response to therapy, but this needs to be analyzed in appropriate studies.

Malignant pleural mesothelioma (MPM) is an aggressive asbestos-related tumour with poor prognosis. To date, a multimodality treatment, including chemotherapy and surgery, with or without radiotherapy, is the gold standard therapy for selected patients with epithelioid and early-stage MPM. In this setting, the goal of surgery is to achieve the macroscopic complete resection, obtained by either extrapleural pneumonectomy or pleurectomy/decortication. Failure, in local and/or distant sites, is one of the major concerns; in fact, there has been no established treatment for the recurrence of MPM after the multimodal approach, and the role of surgery in this context is still controversial. By using electronic databases, studies that included recurrent MPM patients who underwent a second surgery were identified. The endpoints included were: a pattern of recurrence, post-recurrence survival (PRS), and the type of second surgery. When available, factors predicting better PRS and perioperative mortality and morbidity were collected. This systematic review offers an overview of the results that are currently obtained in patients undergoing a second surgery for relapsed MPM, with the aim to provide a comprehensive view on this subject that explores if a second surgery leads to an improvement in survival.

Objectives: we investigated the prevalence and associated factors of depression and complicated grief (CG) among bereaved family members of malignant pleural mesothelioma (MPM) patients in Japan. Methods: Bereaved family members of MPM patients (n = 72) were surveyed. The Japanese version of the Patient Health Questionnaire-9 (PHQ-9) and the Japanese version of the Brief Grief Questionnaire (BGQ) were used to assess depression and complicated grief (CG), respectively. Socio-economic factors, anger toward asbestos, care satisfaction, achievement of good death, and quality of end-of-life care were assessed in relation to depression and CG. Results: In the family members of MPM patients, the frequencies of depression and CG were 19.4% and 15.3%, respectively. The bereaved family members who were not compensated by the asbestos-related health-damage relief system (p = 0.018) and who felt the financial impacts of the patient’s MPM on the family (p = 0.006) had a higher likelihood of depression. The bereaved family members who were not satisfied with the care given when the patient became critical (p = 0.034), who were not compensated by the asbestos-related health-damage relief system (p = 0.020), who felt the financial impact of the patient’s MPM on the family (p = 0.016), and whose deceased relative underwent surgery (p = 0.030) had a higher likelihood of CG. Conclusions: For bereaved family members of MPM patients, routine screening for depression and CG and the provision of grief care are suggested. In addition, for family members of MPM patients, financial support, including the promotion of the asbestos-related health-damage relief system, and improved care for patients who undergo surgery and when patients become critical, are recommended.

Malignant Pleural Mesothelioma (MPM) is a highly aggressive disease whose diagnosis could be challenging and confusing. It could occur with atypical presentations on every examined level. Here, we present three unconventional cases of the complex diagnostic process of MPM that we have experienced during routine practice: a patient with reactive mesothelial hyperplasia mimicking MPM, an unexpected presentation of MPM with persistent unilateral hydropneumothorax, a rare case of MPM in situ. Then, we review the relevant literature on each of these topics. Definitive biomarkers to confidently distinguish MPM from other pleural affections are still demanded. Patients presenting with persistent hydropneumothorax must always be investigated for MPM. MPM in situ is now a reality, and this raises questions about its management.

Objective: This study investigated whether malignant pleural mesothelioma (MPM) patients achieved good deaths and good quality of end-of-life care compared with other cancer patients from the perspective of bereaved family members in Japan. Methods: This cross-sectional study was part of a larger study on the achievement of good deaths of MPM patients and the bereavement of their family members. Bereaved family members of MPM patients in Japan (n = 72) were surveyed. The Good Death Inventory (GDI) was used to assess the achievement of good death. The short version of the Care Evaluation Scale (CES) version 2 was used to assess the quality of end-of-life care. The GDI and CES scores of MPM patients were compared with those of a Japanese cancer population from a previous study. Results: MPM patients failed to achieve good deaths. Only 12.5% of the MPM patients were free from physical pain. The GDI scores of most of the MPM patients were significantly lower than those of the Japanese cancer population. The CES scores indicated a significantly poorer quality of end-of-life care for the MPM patients than the Japanese cancer population. The total GDI and CES scores were correlated (r = 0.55). Conclusions: The quality of end-of-life care for MPM patients remains poor. Moreover, MPM patients do not achieve good deaths from the perspective of their bereaved family members.

Abstract Objective Pleural effusion (PE) is a common feature of malignant pleural mesothelioma. These effusions typically contain lymphocytes and malignant cells. We postulated that the PE would be a source of lymphocytes for analysis of tumor immune milieu. The aim of this study was to compare the phenotype and T cell receptor usage of pleural effusion T cells with paired concurrently drawn peripheral blood lymphocytes. We used multi-parameter flow cytometry and high-throughput T cell receptor sequencing to analyse peripheral blood and pleural effusion mononuclear cells. Results Both CD8+ and CD4+ T cells from effusion showed increased expression of T cell inhibitory receptors PD-1, LAG-3 and Tim-3 compared to blood. Comprehensive T cell receptor sequencing on one of the patients showed a discordant distribution of clonotypes in the antigen-experienced (PD-1+) compartment between effusion and blood, suggesting an enrichment of antigen specific clonotypes in the effusion, with potential as an immunological response biomarker.

Abstract Background Malignant pleural mesothelioma (MPM) is an orphan disease that is difficult to treat using traditional chemotherapy, an approach which has been effective in other types of cancer. Most chemotherapeutics cause DNA damage leading to cell death. Recent discoveries have highlighted a potential role for the p53 tumor suppressor in this disease. Given the pivotal role of p53 in the DNA damage response, here we investigated the predictive power of the p53 interactome model for MPM patients’ stratification. Methods We used bioinformatics approaches including omics type analysis of data from MPM cells and from MPM patients in order to predict which pathways are crucial for patients’ survival. Analysis of the PKT206 model of the p53 network was validated by microarrays from the Mero-14 MPM cell line and RNA-seq data from 71 MPM patients, whilst statistical analysis was used to identify the deregulated pathways and predict therapeutic schemes by linking the affected pathway with the patients’ clinical state. Results In silico simulations demonstrated successful predictions ranging from 52 to 85% depending on the drug, algorithm or sample used for validation. Clinical outcomes of individual patients stratified in three groups and simulation comparisons identified 30 genes that correlated with survival. In patients carrying wild-type p53 either treated or not treated with chemotherapy, FEN1 and MMP2 exhibited the highest inverse correlation, whereas in untreated patients bearing mutated p53, SIAH1 negatively correlated with survival. Numerous repositioned and experimental drugs targeting FEN1 and MMP2 were identified and selected drugs tested. Epinephrine and myricetin, which target FEN1, have shown cytotoxic effect on Mero-14 cells whereas marimastat and batimastat, which target MMP2 demonstrated a modest but significant inhibitory effect on MPM cell migration. Finally, 8 genes displayed correlation with disease stage, which may have diagnostic implications. Conclusions Clinical decisions related to MPM personalized therapy based on individual patients’ genetic profile and previous chemotherapeutic treatment could be reached using computational tools and the predictions reported in this study upon further testing in animal models.

Plain English summary There are new ways to engage people with science and research but many patient support groups and charitable organisations still hold traditional meetings to provide updates on their activities and to report new developments in their field of interest. These meetings often feature presentations given by medical doctors or, in the case of research-focussed organisations, by research scientists. Receiving feedback from people who are confused and sometimes upset by some types of information, and the way it is presented at meetings, made us think about better ways for researchers to discuss their ideas for new research, or share the findings from completed projects, with patients and members of the public. This article describes a method of public engagement called “Meet the Researchers” that enables people to hear about current trends in research face to face with the researchers planning or conducting it. “Meet the Researchers” is designed to promote discussion and allow questions to be asked in a relaxed and informal way, in small groups, which is less daunting than asking questions in front of a conference audience. The aim is to break down the barriers between researchers and patients, and enable conversations that will lead to meaningful engagement and a better understanding of research. Additionally we aim to improve understanding of how results are passed on to doctors and nurses and translated into improvements in patient care. The method was tested with patients and was rated very highly by them in the feedback they gave. Abstract Background Innovative approaches to engaging people with science exist but are often framed around interactive events or social media technologies. Notwithstanding the availability of novel approaches, many patient support groups and charitable organisations continue to hold traditional meetings and seminars to provide information and updates on their activities, and report on developments in their field of interest. In the case of research-focussed organisations, these meetings often take the form of presentations delivered by clinical experts or research scientists. Observation of mesothelioma patients, their relatives, friends and carers attending scientific or clinical-themed meetings has shown that they can be confused, and sometimes distressed, by presentations. This can be due to didactic presentations that are not properly targeted to this audience and a lack of a general overview or summary at the end of meetings that would provide some simple take home messages. This experience motivated the development of a less formal method of sharing complex information and ideas in a simplified manner. “Meet the Researchers” aims to make researchers accessible to patients in order to raise awareness and understanding of research and to explain how research translates into, and informs practice. This approach encourages the use of plain English, removes the tendency to rely on PowerPoint slides to convey the message and moreover, provides an opportunity for researchers to hear patients’ views. Methods Small groups of participants met face to face with the researchers planning or conducting research into their condition, and discussed the topics in a relaxed and informal way. The researchers spent a minimum of 20-min with each group before moving on to the next. Info-graphics on a portable device or printed hand-outs in plain English were allowed but no formal presentations were made. Results Our method has been evaluated using feedback data from three annual events held from 2016 to 2018: 100% of participants indicated that they liked the format “very much”(76.0%) or “quite a lot”(24.0%); 80.4% found the topics “very interesting” and 75.9% found it “very easy” to ask questions. Free text comments revealed themes of ‘hope’ and ‘altruism’. Researchers also reported benefits from participation such as learning about patient’ priorities and networking. Conclusion “Meet the Researchers” provides a unique opportunity for mesothelioma researchers and patients, relatives and carers to interact on a more equal footing. It stimulates discussion, promotes understanding and provides a more informal setting for non-professional participants to ask questions. It is a format that could easily be adapted for use in other conditions.

Background: Malignant pleural mesothelioma (MPM) is an aggressive cancer related to asbestos exposure. Early diagnosis is challenging due to generic symptoms and a lack of biomarkers. We previously demonstrated that mesothelial precursor cells (MPC) characterized by mesothelin (MSLN)+CD90+CD34+ could be implicated in the development of mesothelioma after asbestos exposure. Here, we aimed to determine the clinical significance of detecting MPC in blood for early-stage diagnosis and prognosis of mesothelioma. Methods: Due to the rarity of MPC in blood, it is challenging to identify this cell population using conventional techniques. Hence, we have developed a microfluidic liquid biopsy platform called MesoFind that utilizes an immunomagnetic, mesothelin capture strategy coupled with immunofluorescence to identify rare populations of cells at high sensitivity and precision. To validate our technique, we compared this approach to flow cytometry for the detection of MPC in murine blood and lavage samples. Upon successful validation of the murine samples, we then proceeded to examine circulating MPC in 23 patients with MPM, 23 asbestos-exposed individuals (ASB), and 10 healthy donors (HD) to evaluate their prognostic and diagnostic value. Finding: MPC were successfully detected in the blood of murine samples using MesoFind but were undetectable with flow cytometry. Circulating MPC were significantly higher in patients with epithelioid MPM compared to HD and ASB. The MPC subpopulation, MSLN+ and CD90+, were upregulated in ASB compared to HD suggesting an early role in pleural damage from asbestos. The MPC subpopulation, MSLN+ and CD34+, in contrast, were detected in advanced MPM and associated with markers of poor prognosis, suggesting a predominant role during cancer progression. Interpretation: The identification of circulating MPC presents an attractive solution for screening and early diagnosis of epithelioid mesothelioma. The presence of different subtypes of MPC have a prognostic value that could be of assistance with clinical decisions in patients with MPM. Funding: Princess Margaret Hospital Foundation Mesothelioma Research Fund, Toronto General & Western Hospital Foundation.

Aim: PD-L1 expression and high levels of microsatellite instability (MSI-H) may predict response to checkpoint inhibitors, but their prevalence and prognostic value are unknown in many cancers. Methods: We retrospectively evaluated PD-L1 combined positive score (CPS) and MSI-H and their association with clinical outcomes among patients with ten advanced uncommon cancers. Results: 398 of 426 patients (93%) had a valid PD-L1 result; most (242; 61%) had CPS ≥1. Prevalence of MSI-H tumors was 8/360. Median overall survival was shorter among patients with PD-L1 CPS ≥1 tumors after first-line treatment (23.0 vs 39.7 months, p = 0.014). Conclusion: PD-L1 was commonly expressed in solid tumors, and CPS ≥1 was associated with shorter overall survival. Prevalence of MSI-H was low.

Primary malignant pericardial mesothelioma (PMPM) is a rare cardiac tumor. The patient usually presents with pericardial constriction, usually misdiagnosed and wrongly managed. We present the case of a 21-year-old woman with a history of pericarditis and cardiac tamponade. The patient was referred from a clinic due to nausea, vomiting and ascites with lower extremity edema, soft and watery diarrhea, and right upper quadrant pain. Surgery (sternotomy and partial pericardiectomy) was proposed after looking at the different relevant investigations; it was not until that the patient was operated on that it was established that this wasn't a mere constriction but a malignancy. The patient shortly died after the operation. Pathology made a diagnosis of PMPM. Along with the classical symptoms those who present with level 1 thoracic adenopathy a decision to operate should be very carefully made, this may lead to a misdiagnosis of PMPM which postoperatively results in patient's death.

Abstract Germline mutations in the BRCA-1 associated tumor protein 1 (BAP1) increase susceptibility to mesothelioma and other cancers. We describe a patient with a family history of peritoneal mesothelioma, who developed malignant peritoneal mesothelioma at age 45 in the absence of known asbestos exposure. These findings lead us to hypothesize that the mesothelioma occurred in the setting of germline a BAP1 mutation. This was confirmed by genetic testing. The subsequent therapeutic choices for the patient and testing of at-risk family members highlight the importance of recognizing this genetic syndrome and screening for individuals at high risk.

Malignant pleural mesothelioma (MPM) is an aggressive malignancy, frequently diagnosed at locally-advanced/metastatic stages. Due to a very poor prognosis and limited treatment options, the need to identify new prognostic markers represents a great clinical challenge. The prognostic role of metabolic information derived from Positron Emission Tomography (PET) with 18F-Fluoro-deoxy-glucose (18F-FDG) has been investigated in different MPM settings, however with no definitive consensus. In this comprehensive review, the prognostic value of FDG-PET imaging exclusively performed at staging in MPM patients was evaluated, conducting a literature search on PubMed/MEDLINE from 2010 to 2020. From the 19 selected studies, despite heterogeneity in several aspects, staging FDG-PET imaging emerges as a valuable prognostic biomarker, with higher tumor uptake predictive of worse prognosis, and with volumetric metabolic parameters like Metabolic Tumor Volume, (MTV) and Total Lesion Glycolisis (TLG) performing better than SUVmax. However, PET uptake parameters were not always confirmed as independent prognostic factors, especially in patients previously treated with pleurodesis and with a non-epithelioid histotype. Future prospective studies in larger and clinically homogeneous populations, and using more standardized methods of PET images analysis, are needed to further validate the value of staging FDG-PET in the prognostic MPM stratification, with a potential impact on better patient-tailored treatment planning, in the perspective of personalized medicine.

Malignant mesothelioma (MM) is characterized by poor prognosis and short survival. Extracellular vesicles (EVs) are membrane-bound particles released from cells into various body fluids, and their molecular composition reflects the characteristics of the origin cell. Blood EVs or their miRNA cargo might serve as new minimally invasive biomarkers that would enable earlier detection of MM or treatment outcome prediction. Our aim was to evaluate miRNAs enriched in serum EVs as potential prognostic biomarkers in MM patients in a pilot longitudinal study. EVs were isolated from serum samples obtained before and after treatment using ultracentrifugation on 20% sucrose cushion. Serum EV-enriched miR-103-3p, miR-126-3p and miR-625-3p were quantified using qPCR. After treatment, expression of miR-625-3p and miR-126-3p significantly increased in MM patients with poor treatment outcome (p = 0.012 and p = 0.036, respectively). A relative increase in miR-625-3p expression after treatment for more than 3.2% was associated with shorter progression-free survival (7.5 vs. 19.4 months, HR = 3.92, 95% CI = 1.20–12.80, p = 0.024) and overall survival (12.5 vs. 49.1 months, HR = 5.45, 95% CI = 1.06–28.11, p = 0.043) of MM patients. Bioinformatic analysis showed enrichment of 33 miR-625-3p targets in eight biological pathways. Serum EV-enriched miR-625-3p could therefore serve as a prognostic biomarker in MM and could contribute to a more personalized treatment.

Malignant pleural mesothelioma (MPM) is a highly aggressive pleural tumour which has been epidemiologically linked to occupational exposure to asbestos. MPM is often associated with pleural effusion, which is a common cause of morbidity and whose management remains a clinical challenge. In this review, we analysed the literature regarding the diagnosis and therapeutic options of pleural effusion secondary to mesothelioma. Our aim was to provide a comprehensive view on this subject, and a new algorithm was proposed as a practical aid to clinicians dealing with patients suffering from pleural effusion.

Preoperative identification of unresectable pleural mesothelioma could spare unnecessary surgical intervention and accelerate the initiation of medical treatments. The aim of this study is to determine predictors of unresectability, testing our impression that the contraction of the ipsilateral hemithorax is often associated with exploratory thoracotomy. Between 1994 and 2020, 291 patients undergoing intended macroscopic complete resection for mesothelioma after chemotherapy were retrospectively investigated. Eligible patients (n = 58) presented a preoperative 3 mm slice-thickness chest computed tomography without pleural effusion or hydropneumothorax. Lung volumes (segmented using a semi-automated method), modified-Response Evaluation Criteria in Solid Tumors (RECIST) measurements, and spirometries were collected after chemotherapy. Multivariable analysis was performed to determine the predictors of unresectability. An unresectable disease was found at the time of operation in 25.9% cases. By multivariable analysis, the total lung capacity (p = 0.03) and the disease burden (p = 0.02) were found to be predictors of unresectability; cut-off values were 120.5 mm, respectively. Lung volumes were not confirmed to be associated with unresectability at multivariable analysis, probably due to the correlation with the disease burden (p < 0.001; r = −0.4). Our study suggests that disease burden and total lung capacity could predict MPM unresectability, helping surgeons in recommending surgery or not in a multimodality setting.