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Malignant mesothelioma is a rare type of cancer, in which malignant cells are found in the pleura (the sac lining the chest) or peritoneum (the abdomen). Most people who develop malignant mesothelioma have been exposed to asbestos dust.

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Mesothelioma Molecular Biology

Information Patients and the Public (12 links)

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Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Gerogianni I, Pitaraki E, Jagirdar RM, et al.
2-Deoxy-glucose Enhances the Effect of Cisplatin and Pemetrexed in Reducing Malignant Pleural Mesothelioma Cell Proliferation But Not Spheroid Growth.
Anticancer Res. 2019; 39(7):3809-3814 [PubMed] Related Publications
BACKGROUND/AIM: Malignant pleural mesothelioma (MPM) is a therapy-resistant neoplasm of the pleura. Standard chemotherapy consists of a combination of cisplatin (CPDD) and pemetrexed (PEM). The aim of this study was to assess whether inhibition of aerobic glycolysis by 2-deoxy-glucose (2DG) would enhance the effects of standard chemotherapy.
MATERIALS AND METHODS: MeT-5A, M14K, MSTO and ZL34 cell lines were used. Cell viability with 2DG and cell proliferation and spheroid formation with CPDD+PEM alone and with 2-DG were tested.
RESULTS: Viability with 2-DG was dose-dependent. Cell proliferation with CPDD+PEM on 2D surface was reduced in all cell types, 2-DG inclusion demonstrated a synergistic effect in MSTO and ZL34 cells. Spheroid growth in 3D with CPDD+PEM or CPDD+PEM+2-DG lowered spheroid growth in all cell types.
CONCLUSION: 2-DG synergizes with CPDD+PEM in lowering MPM cell proliferation in 2D to <20%. In 3D MPM spheroid growth 2-DG synergism with CPDD+PEM treatment is not maintained.

Zan X, Wang Y, Shi J, et al.
Biomarkers for detecting malignant pleural mesothelioma: Protocol for a reanalysis of published data based on systematic reviews of diagnostic test accuracy.
Medicine (Baltimore). 2019; 98(24):e16028 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Malignant pleural mesothelioma (MPM) is a highly invasive tumor caused primarily by asbestos exposure. In recent decades, the incidence of MPM has shown an increasing trend, posing a great threat to human health. Although there is currently no effective way to treat MPM, patients can survive for more than 5 years if the tumor is removed early. Several systematic reviews (SRs) have evaluated the diagnostic value of biomarkers for diagnosing MPM. However, no studies have been conducted to analyze the quality of these SRs and it remains unclear which biomarker is the excellent diagnostic test. This study aims to assess the methodological quality of the SRs and reanalyze the published data based on SRs to find the optimal biomarker for the early diagnosis of MPM.
METHODS: A systematic search will be performed in PubMed, Embase.com, the Cochrane Library of Systematic Reviews, and Web of Science to identify SRs reporting value of biomarkers for detecting MPM. We will evaluate the risk of bias of the included SRs according to the Assessment of Multiple Systematic Reviews-2 (AMSTAR-2) instrument. Standard pairwise meta-analysis and adjusted indirect comparison will be used to compare the diagnostic value of different biomarkers.
RESULTS: The results of this study will be submitted to a peer-reviewed journal for publication.
CONCLUSION: This study will reanalyze the published data based on SRs to find a biomarker with the superior diagnostic performance for the diagnosis of MPM.
ETHICS AND DISSEMINATION: Ethics approval and patient consent are not required as this study is an overview based on published systematic reviews.

Colombino E, Capella S, Casalinuovo F, et al.
Malignant peritoneal mesothelioma in a boar who lived in Calabria (Italy): Wild animal as sentinel system of human health.
Sci Total Environ. 2019; 683:267-274 [PubMed] Related Publications
Mesothelioma is a tumor of the serosal membranes described both in human and veterinary medicine. While in humans the relationship between mesothelioma and exposure to asbestos and some other asbestiform minerals is well known, in animals it is still difficult to establish. In this paper a case of malignant peritoneal mesothelioma probably related to asbestos exposure in a wild boar is described. At post-mortem evaluation the peritoneum, diaphragm and serosal surface of liver and kidneys showed isolated to coalescent multiple nodular lesions. Samples from diaphragm, liver and lung were collected to perform microbiological and histological investigations. To assess the presence of asbestos and/or other asbestiform minerals, SEM-EDS investigations were performed on organs and soil samples collected from the area where the wild boar lived. Microbiological investigations were negative for Mycobacterium species. Gross and histological examination were compatible with a biphasic mesothelioma, with nodules composed of epithelioid and sarcomatoid elements with high pleomorphism. Immunohistochemistry revealed only multifocal scattered positivity for WT-1 and D2-40. Asbestos fibres were detected in all samples (organs and soil) by SEM-EDS, demonstrating a potential relationship between the neoplasia and the exposure to naturally occurring asbestos (NOA). In conclusion, the results of the present study are further confirmation that wild animals, such as the boar, are suitable sentinels to indicate the risk of environmental exposure to asbestos for human populations.

Shen PR, Cen J, Qian XQ, et al.
Synchronous occurrence of benign mesothelioma and adenomatoid tumor of uterus: A case report and review of literature.
Medicine (Baltimore). 2019; 98(20):e15746 [PubMed] Free Access to Full Article Related Publications
INTRODUCTION: Synchronous occurrence of benign cystic mesothelioma and adenomatoid tumor of uterus (UAT) are very rare and few cases have been published in the English literature. They are easily misdiagnosed as malignant by clinicians, due to the lack of reports.
PATIENT CONCERNS: A case of benign mesothelial combined with uterus adenomatoid tumor (UAT) in a 48-year-old Chinese woman was reported. Our patient presented with abdominal pain and surgery showed a large subserous mass (12.0 × 11.4 × 9.8 cm) combined with a small intramural solid nodule (2.0 × 1.0 × 1.0 cm), and multiple minute neoplastic growth on the ovary.
DIAGNOSIS: Due to the patient's symptoms, pathological findings, she was diagnosed with synchronous occurrence of benign mesothelioma and UAT.
INTERVENTIONS: We treated her with a total hysterectomy and bilateral adnexectomy.
OUTCOMES: The patient is now in stable condition, without any signs of recurrence during 1 year of follow-up.
LESSONS: Most mesotheliomas are malignant, synchronous occurrence of benign mesothelioma and UAT are extremely rare. And they are often misdiagnosed as malignancy by clinicians. Our case report can improve the awareness of the disease and avoid excessive treatment.

Murphy DJ, Mak SM, Mallia A, et al.
Loco-regional staging of malignant pleural mesothelioma by integrated
Eur J Radiol. 2019; 115:46-52 [PubMed] Related Publications
AIM: To examine the performance of
METHODS: Consecutive subjects with MPM undergoing pre-operative staging with
RESULTS: 10 subjects (9 male, mean age 68 years) with biopsy-proven MPM (9 epithelioid tumours, 1 biphasic) were included. One subject underwent neo-adjuvant chemotherapy between imaging and surgery and was excluded from the clinical versus pathological stage analysis. Pathological staging was concordant with staging by
CONCLUSION: Clinical MPM staging by

Nagamatsu Y, Oze I, Aoe K, et al.
Physician requests by patients with malignant pleural mesothelioma in Japan.
BMC Cancer. 2019; 19(1):383 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Malignant pleural mesothelioma (MPM) is a fatal and rare disease that is caused by the inhalation of asbestos. Treatment and care requests made by MPM patients to their physicians were collected and analyzed.
METHODS: This cross-sectional survey was part of a larger study (N = 133) regarding the quality of life of MPM patients. Specific responses to two open-ended questions related to patients' requests regarding treatment and care were quantified, analyzed and divided into categories based on content.
RESULTS: Responses (N = 217) from MPM patients (N = 73) were categorized into 24 subcategories and then abstracted into 6 categories. The majority of requests were related to patient-physician communication. Patients wanted clear and understandable explanations about MPM and wanted their physician to deliver treatment based on the patient's perspective by accepting and empathizing with their anxiety and pain. Patients expected physicians to be dedicated to their care and establish an improved medical support system for MPM patients.
CONCLUSION: Patients with MPM had a variety of unmet needs from their physicians. Physicians who provide care to MPM patients should receive training in both communication skills and stress management. A multidisciplinary care system that includes respiratory and palliative care for MPM patients should be established.

Huang JW, Li ZH, Wang Z, et al.
Primary malignant mesothelioma of the diaphragm with liver invasion: A case report and review of literature.
Medicine (Baltimore). 2019; 98(15):e15147 [PubMed] Free Access to Full Article Related Publications
RATIONALE: Malignant mesothelioma is a malignant tumor with poor prognosis, which usually originates in the pleura, peritoneum, and pericardial cavity. Mesotheliomas that originate from the diaphragm are very rare. Here, we report a case of primary malignant mesothelioma of the diaphragm with liver invasion.
PATIENT CONCERNS: A 66-year-old woman was admitted to our hospital because of a "liver space-occupying lesion," without any special clinical symptoms. Imaging examinations suggested a cystic-solid mixed lesion in the right lobe of the liver.
DIAGNOSIS: The tumor was diagnosed as epithelioid mesothelioma of the diaphragm with liver invasion.
INTERVENTION: The patient underwent abdominal surgery in our hospital to remove the diaphragmatic mass, liver mass, and part of the diaphragm.
OUTCOMES: The postoperative course was uneventful.
LESSONS: Primary diaphragmatic malignant mesothelioma is very rare and may involve liver or lung tissue and be mistaken for liver or lung tumor. Accurate diagnosis depends on careful pathological examination. Immunohistochemical staining is very useful to distinguish this tumor from other liver or diaphragmatic tumors.

Fedrigotti A, Riccadonna A, Riccadonna D
"Candido's List": the workers of Collotta Cis & Figli at Molina di Ledro in Trento Province, Italy. A tale of magnesia, asbestos and work.
Ann Ist Super Sanita. 2019 Jan-Mar; 55(1):90-93 [PubMed] Related Publications
The study entitled "Candido's List" (La Lista di Candido) is not the work of the three authors alone. A good part of the community is entitled to feel itself coauthor, each for his/her own part, of a research project that has succeeded in blending a variety of different ingredients: history, entrepreneurship, the industrialization of the Trento Province with all its high and low points, personal life stories, medicine, genius, work, women's emancipation, the past but also the present and future. The research comprises an eloquent collection of memories and a variety of iconographic materials; it has now become a book and a travelling exhibition containing the accounts of the people who worked at the Collotta-Cis factory in Molina di Ledro. It starts with the brilliance of Pier Antonio Cassoni, who in 1816 deposited the first patent in the world for the extraction of magnesium carbonate, and closes with the decontamination of the factory site in the late 1980s. A needful section has been set aside for the painful facts relating to the processing of asbestos fibre; a final space, midway between an artistic reading and an interpretation for the future, has seen the involvement of the Circolo Fotoamatori di Ledro, with a photographic itinerary enabling the reader to "virtually' enter the remaining worksites and listen to these spaces "tell" their stories after years of silence. A story in black and white, where the two tones are also messages for reading a complex story, one that it is important to remember.

Katkova LE, Baturina GS, Bondar AA, et al.
Benign Pleural Mesothelial Cells Have Higher Osmotic Water Permeability than Malignant Pleural Mesothelioma Cells and Differentially Respond to Hyperosmolality.
Cell Physiol Biochem. 2019; 52(4):869-878 [PubMed] Related Publications
BACKGROUND/AIMS: Cell volume regulation is a critical mechanism for cell homeostasis and depends on the osmotic water permeability (P
METHODS: In this study we measured the osmotic water permeability of benign human mesothelial cells (MeT-5A) and of epithelioid (M14K) and sarcomatoid (ZL34) malignant pleural mesothelioma (MPM) cells in response to acute hyperosmotic stress. We also assessed the changes in their P
RESULTS: We report that MeT-5A cells have a significantly higher P
CONCLUSION: We provide evidence for a differential regulation of P

Gao R, Wang F, Wang Z, et al.
Diagnostic value of soluble mesothelin-related peptides in pleural effusion for malignant pleural mesothelioma: An updated meta-analysis.
Medicine (Baltimore). 2019; 98(14):e14979 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Soluble mesothelin-related peptide (SMRP) is a widely studied tumor marker for diagnosing malignant pleural mesothelioma (MPM). This study discussed the diagnostic value of SMRPs in pleural effusion (PE) for MPM.
METHODS: Medline, Embase, Web of Science, and Cochrane library system were systematically searched on the data of SMRPs in PE for MPM diagnosis. Pooled diagnostic sensitivity, specificity, and symmetric receiver operating characteristic curve were calculated.
RESULTS: Thirteen studies fulfilled the inclusion criteria and a total of 3359 cases including 759 MPM cases, 1061 non-MM (malignant mesothelioma) malignant PE, and 1539 benign PE were brought into this meta-analysis. The pooled results of SMRPs in PE for diagnosing MPM were as follows: sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.68 (95% confidence interval [CI]: 0.64-0.72), 0.91 (95% CI: 0.86-0.94), 7.8 (95% CI: 5.0-12.0), 0.35 (95% CI: 0.31-0.40), and 22 (95% CI: 14-35), respectively. The area under the summary receiver operating characteristic curves (AUC) was 0.75 (95% CI: 0.72-0.80). Subgroup analyzes revealed that the AUC of cohort group using histological diagnosis could be improved to 0.86 (95% CI: 0.83, 0.89). The Deek's funnel plot asymmetry test showed no publication bias.
CONCLUSION: Although the sensitivity of SMRPs was low, PE-SMRPs can be a good indicator of the existence of MPM.

Sato H, Soh J, Aoe K, et al.
Droplet digital PCR as a novel system for the detection of microRNA‑34b/c methylation in circulating DNA in malignant pleural mesothelioma.
Int J Oncol. 2019; 54(6):2139-2148 [PubMed] Related Publications
Malignant pleural mesothelioma (MPM) is a rare malignancy arising from the pleura that is difficult to diagnose, contributing to its dismal prognosis. Previously, we reported that the degree of microRNA (miR)‑34b/c methylation in circulating DNA is associated with the development of MPM. Herein, we present a newly developed droplet digital PCR (ddPCR)‑based assay for the detection of miR‑34b/c methylation in circulating DNA in patients with MPM. We originally prepared two probes within a short amplicon of 60 bp, designing one from the positive strand and the other from the complementary strand. The two probes functioned cooperatively, and our established assay detected DNA methylation accurately in the preliminary validation. We subsequently verified this assay using clinical samples. Serum samples from 35 cases of MPM, 29 cases of pleural plaque and 10 healthy volunteers were collected from 3 different institutions and used in this study. We divided the samples into 2 groups (group A, n=33; group B, n=41). A receiver‑operating characteristic curve analysis using the samples in group A determined the optimal cut‑off value for the diagnosis of MPM, with a sensitivity of 76.9% and a specificity of 90%. On the other hand, the use of the same criterion yielded a sensitivity of 59.1% and a specificity of 100% in group B, and corresponding values of 65.7 and 94.9% for the entire cohort, indicating a moderate sensitivity and a high specificity. In addition, when the analysis was focused on stage II or more advanced MPM, the sensitivity improved to 81.8%, suggesting the possibility that the methylated allele frequency in MPM may be associated with the stage of disease progression. On the whole, the findings of this study indicate that miR‑34b/c methylation in circulating DNA is a promising biomarker for the prediction of disease progression in patients with MPM.

Muralidhar V, Raghav P, Das P, Goel A
A case from India of pleural malignant mesothelioma probably due to domestic and environmental asbestos exposure: a posthumous report.
BMJ Case Rep. 2019; 12(3) [PubMed] Related Publications
India is the largest consumer of asbestos in the world. There is no report from India of mesothelioma related to asbestos. The case is a 42-year-old man who died of pleural mesothelioma. He was exposed to asbestos domestically and from the environment since birth. Two of his close family members worked in a factory that used asbestos. The living quarter of the family was within the premises of the factory. Asbestos waste was strewn on the grounds surrounding the quarters. After decades of legal battles by workers and families exposed to asbestos, Indian courts have ordered remedial measures and compensation to people, who are exposed to asbestos at work and the environment. Mesothelioma, currently in epidemic proportions in the west where asbestos production was banned in the 1990s, could rise to alarming levels in the next decades in India if the legal remedial measures are not implemented soon.

Yonemura Y, Canbay E, Wakama S, et al.
Prognostic Factors of Malignant Peritoneal Mesothelioma Experienced in Japanese Peritoneal Metastasis Center.
Gan To Kagaku Ryoho. 2019; 46(2):395-399 [PubMed] Related Publications
BACKGROUND AND OBJECTIVES: The current standard of treatment for malignant peritoneal mesothelioma(MPM)is cytoreductive surgery(CRS)plus perioperative intraperitoneal or systemic chemotherapy(comprehensive treatment), The present study was performed to clarify the prognostic factors of PMP after comprehensive treatment.
METHODS: Among 63 patients with MPM, male and female patients were 34 and 29. CRSwas performed in 47 patients and complete cytoreduction(CC-0) was performed in 14(22%)patients. Mean numbers of resected peritoneal sectors and organs were 5.2(1-13), and 2.9(0- 9), respectively. Hyperthermic intraperitoneal chemoperfusion(HIPEC)was performed in 27 patients. Grade 1/2, Grade 3, and Grade 4 complications were experienced in 5, 6, and 3 patients, respectively. One patient died of sepsis, and the mortality rate was 2.3%. Independent prognostic factors for favorable prognosis were performance of HIPEC, peritoneal cancer index (PCI)score C12, no distant metastasis and histologic epithelial type. Relative risk of no HIPEC, PCI score B13, presence of distant metastasis and non epithelial type were 7.69, 22.1, 3.6 and 3.9, respectively.
CONCLUSIONS: Risk factors for death after comprehensive treatment were no HIPEC, PCI score B13, and non epithelial type. However, only 11(17%)patients showed PCI score C12. Accordingly, PCI score should be reducedC12 before CRSby neoadjuvant chemotherapy.

Ladanyi M, Sanchez Vega F, Zauderer M
Loss of BAP1 as a candidate predictive biomarker for immunotherapy of mesothelioma.
Genome Med. 2019; 11(1):18 [PubMed] Free Access to Full Article Related Publications
As trials of immune checkpoint inhibitor (ICI) therapies demonstrate responses in only a minority of pleural mesotheliomas (PlMs) and largely exclude patients with the related peritoneal mesothelioma (PeM), clinicians need predictive biomarkers of response and inclusion of PeM patients in future trials. A new study finds that loss of the deubiquitinase BAP1 in PeM correlates with an inflammatory tumor microenvironment, suggesting that BAP1 status might identify PeM, and possibly PlM, patients who would benefit from ICI therapy.

Blum Y, Meiller C, Quetel L, et al.
Dissecting heterogeneity in malignant pleural mesothelioma through histo-molecular gradients for clinical applications.
Nat Commun. 2019; 10(1):1333 [PubMed] Free Access to Full Article Related Publications
Malignant pleural mesothelioma (MPM) is recognized as heterogeneous based both on histology and molecular profiling. Histology addresses inter-tumor and intra-tumor heterogeneity in MPM and describes three major types: epithelioid, sarcomatoid and biphasic, a combination of the former two types. Molecular profiling studies have not addressed intra-tumor heterogeneity in MPM to date. Here, we use a deconvolution approach and show that molecular gradients shed new light on the intra-tumor heterogeneity of MPM, leading to a reconsideration of MPM molecular classifications. We show that each tumor can be decomposed as a combination of epithelioid-like and sarcomatoid-like components whose proportions are highly associated with the prognosis. Moreover, we show that this more subtle way of characterizing MPM heterogeneity provides a better understanding of the underlying oncogenic pathways and the related epigenetic regulation and immune and stromal contexts. We discuss the implications of these findings for guiding therapeutic strategies, particularly immunotherapies and targeted therapies.

Punatar CB, Jadhav KK, Kumar V, Sagade SN
Malignant mesothelioma of tunica vaginalis without any risk factors: An uncommon case.
J Cancer Res Ther. 2019; 15(Supplement):S167-S169 [PubMed] Related Publications
Malignant mesothelioma (MM) of the tunica vaginalis (TV) is a rare tumor. It is seen in elderly patients, with painless scrotal swelling being the most common presentation. The exact etiology is unknown; a few risk factors have been suggested. Here, we present an uncommon case of MM of TV without any known predisposing factors. We also discuss the possible risk factors, clinical presentation, pathological features and the difficulties in diagnosis, and management of this rare malignancy.

Wang Y, Jiang Z, Yan J, Ying S
HMGB1 as a Potential Biomarker and Therapeutic Target for Malignant Mesothelioma.
Dis Markers. 2019; 2019:4183157 [PubMed] Free Access to Full Article Related Publications
Malignant mesothelioma (MM) is a rare, aggressive, and highly lethal cancer that is substantially induced by exposure to asbestos fibers. High-mobility group box 1 (HMGB1) is an intriguing proinflammatory molecule involved in MM. In this review, we describe the possible crucial roles of HMGB1 in carcinogenic mechanisms based on

Hino O, Abe M, Han B, Yan Y
In commemoration of the 2018 Mataro Nagayo Prize: A road to early diagnosis and monitoring of asbestos-related mesothelioma.
Cancer Sci. 2019; 110(5):1518-1524 [PubMed] Free Access to Full Article Related Publications
Primarily caused by exposure to asbestos, mesothelioma is a typical occupational disease. The latency of mesothelioma is as long as 20-40 years, and the cancer initially progresses mainly along the surfaces of pleura or peritoneum without forming masses. As symptoms do not develop until late stages, it has been challenging to diagnose this disease in its early stages and to carry out complete surgical removal. In responding to Japan's asbestos crisis in the mid-2000s, we have developed and improved ERC/MSLN-based serum and radiological markers and pioneered the use of an N-ERC ELISA kit for screening populations at risk for asbestos exposure. In the present article, we review our research toward early diagnosis of asbestos-related mesothelioma before symptoms develop and share our clinical experience of screening, diagnosing and monitoring of this disease. This paper is dedicated to the author (Dr Okio Hino) to commemorate the honor bestowed upon him as the recipient of the Mataro Nagayo Prize in 2018.

Nakai T, Matsumoto Y, Sasada S, et al.
Cryobiopsy during flex-rigid pleuroscopy: an emerging alternative biopsy method in malignant pleural mesothelioma. A comparative study of pathology.
Jpn J Clin Oncol. 2019; 49(6):559-566 [PubMed] Related Publications
BACKGROUND: Malignant pleural mesothelioma (MPM) is rarely an asbestos-related cancer with a poor prognosis that is difficult to distinguish from some benign conditions by using conventional biopsy techniques. The purpose of this study was to evaluate the utility of a novel biopsy technique using a cryoprobe during flex-rigid pleuroscopy for diagnosing MPM.
METHODS: Consecutive patients who underwent pleural cryobiopsy during flex-rigid pleuroscopy from June through November 2017 to diagnose the cause of pleural effusion were collected. From these, cases ultimately diagnosed as MPM were selected. Pleural biopsies were performed by using conventional instruments followed by a cryoprobe. The obtained samples were histologically examined and compared with regard to the quality (sample size, tissue depth, and crush rate), immunohistochemical (IHC) staining, and p16 by fluorescence in situ hybridization (FISH).
RESULTS: In total, five patients ultimately diagnosed as MPM were enrolled. The sample collected was significantly larger for cryobiopsy than conventional biopsy (18.9 mm2 vs. 6.7 mm2, P < 0.001). Full-thickness biopsies were achieved in four cases by using cryobiopsy compared with one case by conventional biopsy. Moreover, the crush rate was significantly less for cryobiopsy than conventional biopsy (9% vs. 35%, P < 0.001). The results of IHC staining and p16 by FISH were similar between biopsy techniques. Cryobiopsy successfully led to accurate diagnosis of MPM in all cases, whereas conventional biopsy was diagnostic in one case. No severe complications developed after either biopsy technique.
CONCLUSION: Cryobiopsy during flex-rigid pleuroscopy is a feasible and convenient biopsy technique that supports precise diagnosis of MPM.

Miyata T, Fujiwara Y, Nishijima K, et al.
Localized multiple malignant epithelioid peritoneal mesotheliomas arising from the hepatoduodenal ligament and diaphragm: a case report.
J Med Case Rep. 2019; 13(1):66 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Malignant peritoneal mesothelioma is a rare aggressive tumor of the peritoneum. We report a rare case of resection of multiple localized malignant peritoneal mesotheliomas.
CASE PRESENTATION: A 55-year-old Japanese woman was admitted to our hospital because liver tumors were detected by abdominal ultrasonography during a screening examination. Blood examination findings, including tumor makers, were within normal ranges. She had no evidence of exposure to asbestos. Computed tomography showed four hypervascular, round liver tumors, one in the lateral liver segment adjacent to the hepatic hilus, and the other three on the liver surface. Computed tomography angiography revealed that the tumor in the lateral segment had strong enhancement and was fed from the left gastric artery. In contrast, the other tumors showed no enhancement, and were fed from the right inferior phrenic artery. Abnormal accumulation was identified in the four tumors only with
CONCLUSIONS: In general, malignant peritoneal mesotheliomas are classified as diffuse tumors, which are often unresectable and have a poor prognosis. However, early diagnosis and treatment, particularly with the localized type, as in our patient, could lead to long-term survival of the patient. We recommend that multiple malignant epithelioid mesotheliomas be included in the differential diagnosis for patients with subcapsular hepatic tumors.

Vivoda Tomšič M, Bisdas S, Kovač V, et al.
Dynamic contrast-enhanced MRI of malignant pleural mesothelioma: a comparative study of pharmacokinetic models and correlation with mRECIST criteria.
Cancer Imaging. 2019; 19(1):10 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare and aggressive thoracic malignancy that is difficult to cure. Dynamic contrast-enhanced (DCE) MRI is a functional imaging technique used to analyze tumor microvascular properties and to monitor therapy response. Purpose of this study was to compare two tracer kinetic models, the extended Tofts (ET) and the adiabatic approximation tissue homogeneity model (AATH) for analysis of DCE-MRI and examine the value of the DCE parameters to predict response to chemotherapy in patients with MPM.
METHOD: This prospective, longitudinal, single tertiary radiology center study was conducted between October 2013 and July 2015. Patient underwent DCE-MRI studies at three time points: prior to therapy, during and after cisplatin-based chemotherapy. The images were analyzed using ET and AATH models. In short-term follow-up, the patients were classified as having disease control or progressive disease according to modified response evaluation criteria in solid tumors (mRECIST) criteria. Receiver operating characteristic curve analysis was used to examine specificity and sensitivity of DCE parameters for predicting response to therapy. Comparison tests were used to analyze whether derived parameters are interchangeable between the two models.
RESULTS: Nineteen patients form the study population. The results indicate that the derived parameters are not interchangeable between the models. Significant correlation with response to therapy was found for AATH-calculated median pre-treatment efflux rate (k
CONCLUSION: Both models show potential in predicting response to therapy in MPM. High pre-treatment k

Mlika M, Zorgati M, BenKhelil M, Mezni FE
About the diagnostic value of BAP-1 antibody in malignant pleural mesothelioma: a meta-analysis.
J Immunoassay Immunochem. 2019; 40(3):269-282 [PubMed] Related Publications
BACKGROUND: The positive diagnosis of MPM is based on morphologic features coupled with immunohistochemical findings. Many antibodies have been published especially in order to differentiate between malignant tumors and atypical mesothelial hyperplasia. BAP-1 is a BRCA1-binding protein whose loss of expression was frequently reported in MPM. Our aim was to assess the diagnostic value of this antibody in comparison to the most sensitive diagnostic antibody represented by the calretinin antibody.
METHODS: We performed a meta-analysis using the Meta-Disc software 5.1.32.
RESULTS: According to our inclusion criteria, 19 studies with 11 studies dealing with BAP1 antibody and 8 studies dealing with calretinin antibody were included. The SEN of BAP 1 and calretinin antibodies was respectively estimated to 54.6% and 86.5%. The SPE reached respectively 95.7% and 76.6%. The dOR was estimated respectively to 23.664 and 38.8. The I-square revealed a heterogeneity of the parameters studied. The metaregression analysis revealed as covariates the amplification system and the histologic subtype as causing effects of heterogeneity for BAP1 antibodies and histologic subtype and chromogene as causing effects of heterogeneity for calretinin antibody.
CONCLUSION: This meta-analysis revealed that BAP1 antibody should be associated with more sensitive antibodies in order to assess the diagnosis.

Kim M, Kim HS
Clinicopathological Characteristics of Well-differentiated Papillary Mesothelioma of The Peritoneum: A Single-institutional Experience of 12 Cases.
In Vivo. 2019 Mar-Apr; 33(2):633-642 [PubMed] Free Access to Full Article Related Publications
BACKGROUND/AIM: Well-differentiated papillary mesothelioma (WDPM) is histologically characterized by papillary architecture with fibrovascular cores, lined by bland mesothelial cells. We recently experienced a case of WDPM associated with multiple peritoneal inclusion cysts, which prompted us to initiate a comprehensive review of previously diagnosed WDPM cases.
MATERIALS AND METHODS: The clinicopathological characteristics and immunophenotype of 12 cases of peritoneal WDPM were investigated using a review of electronic medical records, pathological examination, and immunostaining.
RESULTS: The patients' ages ranged from 23 to 75 years. No patient had endometriosis or a previous history of asbestos exposure. Ten tumors were detected incidentally during surgery for other causes. Most tumors appeared as a small, single nodule on the peritoneal surface, but in three cases, WDPM presented as multiple lesions. All but one patient had no symptoms. All the patients examined are still well without postoperative recurrence. Histologically, all cases demonstrated typical papillary architecture with fibrovascular cores. The mesothelial cells lining the papillae consisted mostly of single row of cells, although areas of proliferation to multiple layers were observed in a few cases. Their nuclei appeared bland, but two cases exhibited mild nuclear atypia and prominent nucleoli. Immunostaining revealed that the mesothelial cells were positive for D2-40, cytokeratin 5/6, cytokeratin 7, and Wilms' tumor 1.
CONCLUSION: We herein demonstrated the clinicopathological characteristics of peritoneal WDPMs. WDPM has distinct pathological features. Although all cases we examined were uneventful after surgery, further surveillance is recommended since the biological behavior of WDPM is still uncertain.

Sudo H, Tsuji AB, Sugyo A, et al.
Therapeutic efficacy evaluation of radioimmunotherapy with
Cancer Sci. 2019; 110(5):1653-1664 [PubMed] Free Access to Full Article Related Publications
Podoplanin is a type I transmembrane sialomucin-like glycoprotein that is highly expressed in malignant mesothelioma. The rat-human chimeric antibody NZ-12 has high affinity for human podoplanin and antibody-dependent cellular cytotoxicity and is applicable for radioimmunotherapy (RIT) to enhance the antitumor effect. In the present study, we evaluated the in vivo and in vitro properties of radiolabeled NZ-12 and the antitumor effect of RIT with

Shrestha R, Nabavi N, Lin YY, et al.
BAP1 haploinsufficiency predicts a distinct immunogenic class of malignant peritoneal mesothelioma.
Genome Med. 2019; 11(1):8 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Malignant peritoneal mesothelioma (PeM) is a rare and fatal cancer that originates from the peritoneal lining of the abdomen. Standard treatment of PeM is limited to cytoreductive surgery and/or chemotherapy, and no effective targeted therapies for PeM exist. Some immune checkpoint inhibitor studies of mesothelioma have found positivity to be associated with a worse prognosis.
METHODS: To search for novel therapeutic targets for PeM, we performed a comprehensive integrative multi-omics analysis of the genome, transcriptome, and proteome of 19 treatment-naïve PeM, and in particular, we examined BAP1 mutation and copy number status and its relationship to immune checkpoint inhibitor activation.
RESULTS: We found that PeM could be divided into tumors with an inflammatory tumor microenvironment and those without and that this distinction correlated with haploinsufficiency of BAP1. To further investigate the role of BAP1, we used our recently developed cancer driver gene prioritization algorithm, HIT'nDRIVE, and observed that PeM with BAP1 haploinsufficiency form a distinct molecular subtype characterized by distinct gene expression patterns of chromatin remodeling, DNA repair pathways, and immune checkpoint receptor activation. We demonstrate that this subtype is correlated with an inflammatory tumor microenvironment and thus is a candidate for immune checkpoint blockade therapies.
CONCLUSIONS: Our findings reveal BAP1 to be a potential, easily trackable prognostic and predictive biomarker for PeM immunotherapy that refines PeM disease classification. BAP1 stratification may improve drug response rates in ongoing phases I and II clinical trials exploring the use of immune checkpoint blockade therapies in PeM in which BAP1 status is not considered. This integrated molecular characterization provides a comprehensive foundation for improved management of a subset of PeM patients.

Cova E, Pandolfi L, Colombo M, et al.
Pemetrexed-loaded nanoparticles targeted to malignant pleural mesothelioma cells: an in vitro study.
Int J Nanomedicine. 2019; 14:773-785 [PubMed] Free Access to Full Article Related Publications
Purpose: Malignant pleural mesothelioma (MPM) is an aggressive tumor characterized by poor prognosis. Its incidence is steadily increasing due to widespread asbestos exposure. There is still no effective therapy for MPM. Pemetrexed (Pe) is one of the few chemotherapeutic agents approved for advanced-stage disease, although the objective response to the drug is limited. The use of gold nanoparticles (GNPs) as a drug delivery system promises several advantages, including specific targeting of malignant cells, with increased intracellular drug accumulation and reduced systemic toxicity, and, in the case of MPM, direct treatment administration into the pleural space. This study aims at exploring CD146 as a potential MPM cell-specific target for engineered Pe-loaded GNPs and to assess their effectiveness in inhibiting MPM cell line growth.
Methods: MPM cell lines and primary cultures obtained by pleural effusions from MPM patients were assayed for CD146 expression by flow cytometry. Internalization by MPM cell lines of fluorescent dye-marked GNPs decorated with a monoclonal anti CD146 coated GNPs (GNP-HC) was proven by confocal microscopy. The effects of anti CD146 coated GNPs loaded with Pe (GNP-HCPe) on MPM cell lines were evaluated by cell cycle (flow cytometry), viability (MTT test), clonogenic capacity (soft agar assay), ROS production (electric paramagnetic resonance), motility (wound healing assay), and apoptosis (flow cytometry).
Results: GNP-HC were selectively uptaken by MPM cells within 1 hour. MPM cell lines were blocked in the S cell cycle phase in the presence of GNP-HCPe. Both cell viability and motility were significantly affected by nanoparticle treatment compared to Pe. Apoptotic rate and ROS production were significantly higher in the presence of nanoparticles. Clonogenic capacity was completely inhibited following nanoparticle internalization.
Conclusion: GNP-HCPe treatment displays in vitro antineoplastic action and is more effective than Pe alone in inhibiting MPM cell line malignant phenotype. The innovative use of specifically targeted GNPs opens the perspective of local intrapleural administration to avoid normal cell toxicity and enhance chemotherapy efficacy.

Pelclová D
Diagnostics and acknowledgement of occupational diseases - topics and challenges in the Czech Republic.
Cas Lek Cesk. 2018; 157(8):396-399 [PubMed] Related Publications
The causes of occupational diseases are changing, thats why a regular update of Czech List of Occupational Diseases is needed. New compensable occupational diseases, such as cancer of the larynx and ovarian cancer due to asbestos, and chronic obstructive pulmonary diseases due to black coal dust were included in the last two updates of the Czech List. The need of an early examination at the Centers of Occupational Diseases is stressed in this article, especially before a surgery or other treatment of epicondylitis and carpal tunnel syndrome. These treatments may suppress the diagnostic hallmarks requested for acknowledgements of these disorders. Extrinsic allergic alveolitis, allergic rhinitis and bronchial asthma are underdiagnosed, and isocyanates belong among the key factors. Only about 10 % patients with mesotheliomas due to asbestos are compensated. The latency in cancers due to asbestos may reach more than 50 years.

Weber DG, Brik A, Casjens S, et al.
Are circulating microRNAs suitable for the early detection of malignant mesothelioma? Results from a nested case-control study.
BMC Res Notes. 2019; 12(1):77 [PubMed] Free Access to Full Article Related Publications
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.

Salo SAS, Ilonen I, Laaksonen S, et al.
Malignant Peritoneal Mesothelioma: Treatment Options and Survival.
Anticancer Res. 2019; 39(2):839-845 [PubMed] Related Publications
BACKGROUND: Malignant peritoneal mesothelioma (MPeM) is a rare type of cancer with a poor prognosis. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) have been shown to improve survival. Treatment and survival of patients with MPeM have not been previously studied in Finland.
MATERIALS AND METHODS: The data consisted of all patients diagnosed with MPeM during years 2000-2012 in Finland, including cancer notifications, death certificates and information about asbestos exposure.
RESULTS: Among 50/94 (53.2%) patients treated for MPeM, 44/50 (88.0%) were treated palliatively, 4/50 (8.0%) with radical surgery and chemotherapy, and 2/50 (4.0%) with CRS plus HIPEC. Five-year survival was 50.0% for those treated with CRS plus HIPEC and 75.0% for those treated with radical surgery and chemotherapy. Radical surgery with chemotherapy was associated with significantly longer survival compared to radiation (p=0.008), chemotherapy and radiation (p=0.043), surgery, chemotherapy and radiation (p=0.039), and palliative surgery (p=0.009).
CONCLUSION: Treatment of MPeM is heterogenic in Finland. CRS plus HIPEC, and radical surgery with chemotherapy seem to increase the survival. Patients considered candidates for radical surgery should be sent to specialized centers for further assessment.

Nakayama K, Seike M, Noro R, et al.
Tenascin XB Is a Novel Diagnostic Marker for Malignant Mesothelioma.
Anticancer Res. 2019; 39(2):627-633 [PubMed] Related Publications
BACKGROUND/AIM: Malignant mesothelioma (MM) is an aggressive tumor with poor prognosis. The establishment of a new diagnostic and therapeutic approach for MM is expected. This study investigated the diagnostic significance of tenascin XB (TNXB) for MM.
MATERIALS AND METHODS: TNXB gene expression was found to be significantly higher in MM tumor tissues compared to paired normal tissues, as assessed by the Gene Expression Omnibus database. The inhibition of TNXB using small interfering RNAs suppressed the proliferation and colony formation of MM cells. Expression of TNXB and calretinin, a current diagnostic marker of MM, was evaluated by immunohistochemistry.
RESULTS: The sensitivity and specificity of TNXB for MM were 80.0% and 69.5%, respectively. When the detection of TNXB was combined with that of calretinin, 83.3% of MM cases were detected.
CONCLUSION: These findings suggest that TNXB is a novel diagnostic biomarker for MM. A combination of detecting TNXB and calretinin may be useful for the differential diagnosis of MM from lung adenocarcinoma.

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