bims-mesote 2022-06-26 papers

Issue of 2022–06–26
six papers selected by
Laura Mannarino, Humanitas Research

J Clin Med. 2022 Jun 10. pii: 3340. [Epub ahead of print]11(12):

Second Surgery for Recurrent Malignant Pleural Mesothelioma after Multimodality Treatment: A Systematic Review.

Alice Bellini, Sara Mazzarra, Sara Sterrantino, Desideria Argnani, Franco Stella.

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.

Keywords: mesothelioma; post-recurrence survival; recurrence; second surgery

DOI: https://doi.org/10.3390/jcm11123340

Cells. 2022 Jun 10. pii: 1892. [Epub ahead of print]11(12):

Aquaporin-6 May Increase the Resistance to Oxidative Stress of Malignant Pleural Mesothelioma Cells.

Giorgia Pellavio, Simona Martinotti, Mauro Patrone, Elia Ranzato, Umberto Laforenza.

Malignant pleural mesothelioma (MPM) is an aggressive cancer of the pleural surface and is associated with previous asbestos exposure. The chemotherapy drug is one of the main treatments, but the median survival ranges from 8 to 14 months from diagnosis. The redox homeostasis of tumor cells should be carefully considered since elevated levels of ROS favor cancer cell progression (proliferation and migration), while a further elevation leads to ferroptosis. This study aims to analyze the functioning/role of aquaporins (AQPs) as a hydrogen peroxide (H2O2) channel in epithelial and biphasic MPM cell lines, as well as their possible involvement in chemotherapy drug resistance. Results show that AQP-3, -5, -6, -9, and -11 were expressed at mRNA and protein levels. AQP-6 was localized in the plasma membrane and intracellular structures. Compared to normal mesothelial cells, the water permeability of mesothelioma cells is not reduced by exogenous oxidative stress, but it is considerably increased by heat stress, making these cells resistant to ferroptosis. Functional experiments performed in mesothelioma cells silenced for aquaporin-6 revealed that it is responsible, at least in part, for the increase in H2O2 efflux caused by heat stress. Moreover, mesothelioma cells knocked down for AQP-6 showed a reduced proliferation compared to mock cells. Current findings suggest the major role of AQP-6 in providing mesothelioma cells with the ability to resist oxidative stress that underlies their resistance to chemotherapy drugs.

Keywords: Hyper7 probe; biphasic; epithelioid; gene silencing; hydrogen peroxide; peroxiporins; tumor proliferation

DOI: https://doi.org/10.3390/cells11121892

J Clin Med. 2022 Jun 13. pii: 3380. [Epub ahead of print]11(12):

Depression and Complicated Grief, and Associated Factors, of Bereaved Family Members of Patients Who Died of Malignant Pleural Mesothelioma in Japan.

Yasuko Nagamatsu, Yumi Sakyo, Edward Barroga, Riwa Koni, Yuji Natori, Mitsunori Miyashita.

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.

Keywords: asbestos; bereaved; complicated grief; depression; family; grief; mesothelioma

DOI: https://doi.org/10.3390/jcm11123380

BMC Cancer. 2022 Jun 23. 22(1): 693

Malignant pleural mesothelioma: treatment patterns and humanistic burden of disease in Europe.

Adam Moore, Bryan Bennett, Gavin Taylor-Stokes, Laura McDonald, Melinda J Daumont.

BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive and rare tumour with poor prognosis. Most patients are diagnosed with advanced disease and there is a paucity of data on the humanistic burden of MPM in terms of impact on health-related quality of life (HRQoL) and activity. This study examined real-world treatment patterns and humanistic disease burden of MPM in Europe.
METHODS: Physicians abstracted demographic/clinical characteristics and treatment data from MPM-patient medical records; MPM patients self-completed a questionnaire including symptoms, 3-level-EQ-5D questionnaire and Visual Analogue Scale (VAS), Lung Cancer Symptom Scale for Mesothelioma (LCSS-Meso), and Work Productivity and Activity Impairment (WPAI) questionnaire.
RESULTS: Physicians (n = 171) abstracted data of 1390 patients; 767/1390 patients self-completed questionnaires. Patients were elderly with advanced, unresectable MPM. Treatment patterns followed guidelines with most (81%) patients receiving platinum+antifolate chemotherapy at first line (1 L). Maintenance treatment use was high (51.1%) despite no recommended maintenance therapies. Symptom burden was high and health states and HRQoL were poor at 1; declining further with progression. Overall mean (SD): LCSS-Average Symptom Burden Index score was 48.8 (19.3; n = 758); EQ-5D Utility Index score was 0.510 (0.349; n = 763); EQ-5D VAS score was 54.2 (20.3;n = 766); LCSS-3-Item Global Index score was 143.2 (64.5; n = 762); LCSS-normal activities score was 51.9 (24.6;n = 765); WPAI-activity impairment was 56.0% (23.2%; n = 737).
CONCLUSION: The humanistic burden of MPM is high, despite treatments being prescribed as per available guidance. Treatments that delay progression and provide palliation of symptoms are most likely to improve/maintain HRQoL.

Keywords: Disease management; Health-related quality of life; Malignant pleural mesothelioma; Real-world; Treatment

DOI: https://doi.org/10.1186/s12885-022-09750-7

Environ Health. 2022 Jun 18. 21(1): 60

Pleural mesothelioma risk by industry and occupation: results from the Multicentre Italian Study on the Etiology of Mesothelioma (MISEM).

Enrica Migliore, Dario Consonni, Susan Peters, Roel C H Vermeulen, Hans Kromhout, Antonio Baldassarre, Domenica Cavone, Elisabetta Chellini, Corrado Magnani, Carolina Mensi, Enzo Merler, Marina Musti, Alessandro Marinaccio, Dario Mirabelli.

BACKGROUND: The Italian mesothelioma registry (ReNaM) estimates mesothelioma incidence and addresses its etiology by assessing cases' exposures but cannot provide relative risk estimates.
OBJECTIVES: i) To estimate pleural mesothelioma relative risk by industry and occupation and by ReNaM categories of asbestos exposure; and ii) to provide quantitative estimates of the exposure-response relationship.
METHODS: A population-based mesothelioma case-control study was conducted in 2012-2014 in five Italian regions. Cases and age and gender frequency-matched controls were interviewed using a standard ReNaM questionnaire. Experts coded work histories according to international standard classifications of industries/occupations and assigned asbestos exposure according to ReNaM categories. Job codes were further linked to SYN-JEM, a quantitative job-exposure matrix. Cumulative exposure (CE, f/mL-years) was computed by summing individual exposures over lifetime work history. Unconditional logistic regression analyses adjusted by gender, centre and age were fitted to calculate odds ratios (OR) and 95% confidence intervals (CI).
RESULTS: Among men we observed increased risks of mesothelioma in many industries and associated occupations, including: asbestos-cement (OR = 3.43), manufacture of railroad equipment (OR = 8.07), shipbuilding and repairing (OR = 2.34), iron and steel mills (OR = 2.15), and construction (OR = 1.94). ORs by ReNaM exposure categories were as follows: definite/probable occupational exposure (OR = 15.8, men; OR = 8.80, women), possible occupational (OR = 2.82, men; OR = 3.70, women), sharing home with an exposed worker (OR = 2.55, men; OR = 10.3, women), residential (OR = 2.14, men; OR = 3.24, women). Based on SYN-JEM, mesothelioma risk increased by almost 30% per f/mL-year (OR = 1.28, CI 1.16-1.42).
CONCLUSIONS: Out study involved five regions with historically different types and levels of industrial development, encompassing one third of the Italian population and half of Italian mesothelioma cases. As expected, we found increased pleural mesothelioma risk in the asbestos industry and in trades with large consumption of asbestos materials. Clear associations were found using both qualitative (ReNaM classifications) and quantitative estimates (using SYN-JEM) of past asbestos exposure, with clear evidence of an exposure-response relationship.

Keywords: Asbestos; Case–control study; Exposure assessment; Occupational exposure; Pleural mesothelioma

DOI: https://doi.org/10.1186/s12940-022-00869-5