Journal of Clinical Medicine

About the journal

Publisher: MDPI AG
Published: 2012 to the present, Switzerland
Language: English
ISSN: 2077-0383 (electronic)
Its record in the NLM Catalog

2020s

Lung Cancer Screening in a Population from Northeast Italy Exposed to Both Asbestos and Smoking: A Cost-Effectiveness Analysis. R. Cosulich, C. Thomas, F. Barbiero, et al. 2026;15(8). PubMed · Publisher · Free full text

Abstract

Background: Past workplace exposure to asbestos in combination with tobacco smoking has increased the risk of lung cancer for some residents in an area within the Friuli Venezia Giulia region, Northeast Italy. In light of studies showing that lung cancer screening (LCS) with low-dose computed tomography (LDCT) can reduce mortality, local stakeholders and decision-makers decided to assess the potential benefits, harms and cost-effectiveness of a single round of LCS with LDCT versus standard care among people aged 55 to 80 who were formerly exposed to asbestos and with at least 10 pack-years of smoking. Methods: An economic model was developed using a decision tree connected to a Markov cohort model. The primary outcome was the incremental cost per additional quality-adjusted life year (QALY). Other outcomes included the number of life years saved, the number of deaths averted and overdiagnosis. Results: Per 10,000 people screened, the intervention led to 395 additional QALYs (95% credible interval: 129 to 831) and incremental total costs of EUR 1,086,345 (95% credible interval: -852,607 to 2,155,826). The incremental cost per QALY gained was EUR 2750. There was a probability of cost-effectiveness of 99.5% relative to a threshold of EUR 25,000. Conclusions: The model estimated that the intervention was cost-effective. The model's simplifications and limitations should be considered when interpreting the findings in relation to policy-making decisions. Further research could include the costs and benefits of incidental findings and could assess the cost-effectiveness of repeated rounds of screening for the same population.
Post-Recurrence Treatment Patterns and Outcomes After Curative-Intent Multimodality Strategy in Patients with Pleural Mesothelioma: A Retrospective Cohort Study. O. Illini, H. Fabikan, I. Berghammer, et al. 2026;15(20). PubMed · Publisher · Free full text

Abstract

Background: Disease recurrence is common after surgery for pleural mesothelioma (PM), and the evidence guiding post-recurrence management remains limited. Methods: We conducted a retrospective, single-center cohort study including patients with PM treated within a curative-intent multimodality treatment pathway including surgery aiming for a macroscopic complete resection when feasible between 2001 and 2024. Post-recurrence treatments were categorized as best supportive care only (BSC), systemic therapy alone, or local with or without systemic therapy. Survival and disease-free outcomes were analyzed in relation to treatment patterns and clinical prognostic factors. Results: Among 67 patients with a median follow-up time of 107 months from surgery, 58 (86.6%) developed disease recurrence. At first recurrence, 21 patients (36%) received local with or without systemic therapy, 26 (45%) systemic therapy alone, and 11 (19%) BSC. The median post-recurrence survival was 21.7 months for patients receiving local with or without systemic therapy, 10.8 months for systemic therapy alone, and 1.6 months for BSC. Lung-sparing surgery and a disease-free interval of at least 12 months were associated with improved post-recurrence survival and post-recurrence progression-free survival. Conclusions: In this real-world cohort of patients with PM and extended follow-up, active post-recurrence treatment was associated with longer post-recurrence survival in selected patients. However, conclusions regarding their comparative effectiveness are limited by the retrospective design, incomplete recurrence-related data, and patient selection at recurrence.
Prognostic Significance of B7-H3, TROP2, and p16 Expression in Pleural Mesothelioma: Clinicopathological Correlations and Survival Outcomes. N. Tas, R.O. Yüceer, T. Koc, et al. 2026;15(20). PubMed · Publisher · Free full text

Abstract

Background: Pleural mesothelioma (PM) is an aggressive malignancy with considerable biological heterogeneity and few established prognostic biomarkers. We evaluated the clinicopathological and prognostic relevance of B7-H3, TROP2, and p16 expression in PM. Methods: This retrospective study included 50 patients with histologically confirmed PM diagnosed between 2016 and 2025. Immunohistochemical expression of B7-H3, TROP2, and p16 was evaluated using an immunoreactivity scoring system. Associations with clinicopathological features were examined, and overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan-Meier and Cox proportional hazards methods. Results: High B7-H3, TROP2, and p16 expression was observed in 78%, 18%, and 20% of tumors, respectively. High B7-H3 expression was significantly associated with asbestos exposure, chemotherapy, and tumor stage. Patients with high B7-H3 expression had shorter median OS (11.0 vs. 42.0 months; p < 0.001) and PFS (11.0 vs. 40.0 months; p = 0.004) than those with negative/low expression. Neither TROP2 nor p16 expression was significantly associated with survival. In a parsimonious multivariable Cox model, high B7-H3 expression remained significantly associated with poorer OS after adjustment for disease stage (HR = 4.42, 95% CI: 1.29-15.21, p = 0.018). Conclusions: B7-H3 is frequently expressed in PM and was associated with poorer survival, including after adjustment for disease stage. These findings support further investigation of B7-H3 as a potential prognostic biomarker and therapeutic target in PM.
A Promising Prognostic Indicator for Pleural Mesothelioma: Pan-Immuno-Inflammation Value. S. Yaşar, F. Yılmaz, Ö.D. Tatar, et al. 2025;14(15). PubMed · Publisher · Free full text

Abstract

Background: Pleural mesothelioma (PM) is a type of cancer that is difficult to diagnose and treat. Patients may have vastly varying prognoses, and prognostic factors may help guide the clinical approach. As a recently identified biomarker, the pan-Immune-Inflammation-Value (PIV) is a simple, comprehensive, and peripheral blood cell-based biomarker. Methods: The present study represents a retrospective observational analysis carried out within a single-center setting. Ninety-five patients with PM stages I-IV were enrolled in the study. We analyzed the correlation between patients' demographic characteristics, clinicopathological factors such as histological subtypes, surgery status, tumor thickness, blood-based parameters, and treatment options with their prognoses. PIV was calculated by the following formula: (neutrophil count × monocyte count × platelet count)/lymphocyte count. Additionally, blood-based parameters were used to calculate the platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and systemic immune inflammation index (SII). Results: We categorized the patients into two groups, low PIV group (PIV ≤ 732.3) and high PIV group (PIV > 732.3) according to the determined cut-off value, which was defined as the median. It was revealed that high PIV was associated with poor survival outcomes. The median follow-up period was 15.8 months (interquartile range, IQR, 7.1 to 29.8 months). The median overall survival (OS) was significantly longer in patients in the low PIV group (median 29.8 months, 95% confidence interval (CI), 15.6 to 44) than the high PIV group (median 14.7 months, 95% CI, 10.8 to 18.6 p < 0.001). Furthermore, the study revealed that patients with low PIV, NLR, and SII values were more likely to be eligible for surgery and were diagnosed at earlier stages. Additionally, these markers were identified as potential predictors of disease-free survival (DFS) in the surgical cohort and of treatment response across the entire patient population. Conclusions: In addition to well-established clinical factors such as stage, histologic subtype, resectability, and Eastern Cooperative Oncology Group (ECOG) performance status (PS), PIV emerged as an independent and significant prognostic factor of overall survival (OS) in patients with PM. Moreover, PIV also demonstrated a remarkable independent prognostic value for disease-free survival (DFS) in this patient population. Additionally, some clues are provided for conditions such as treatment responses, staging, and suitability for surgery. As such, in this cohort, it has outperformed the other blood-based markers based on our findings. Given its ease of calculation and cost-effectiveness, PIV represents a promising and practical prognostic tool in the clinical management of pleural mesothelioma. It can be easily calculated using routinely available laboratory parameters for every cancer patient, requiring no additional cost or complex procedures, thus facilitating its integration into everyday clinical practice.
Malignant Pleural Mesothelioma: A 2025 Update. G. Cardillo, D. Waller, S. Tenconi, et al. 2025;14(3). Editorial PubMed · Publisher · Free full text

Abstract

The incidence of pleural mesothelioma (PM) is slightly increasing, with 2417 new cases/year worldwide [...].
Pleurectomy/Decortication Versus Extrapleural Pneumonectomy in Pleural Mesothelioma: A Systematic Review and Meta-Analysis of Survival, Mortality, and Surgical Trends. M. Brivio, M. Chiari, C. Bardoni, et al. 2025;14(17). Review PubMed · Publisher · Free full text

Abstract

Background: The optimal surgical approach for malignant pleural mesothelioma (PM) remains a topic of debate. While extrapleural pneumonectomy (EPP) offers radical resection, it is associated with significant morbidity. Pleurectomy/decortication (P/D) is less extensive but may offer comparable oncologic outcomes with reduced perioperative risk. This study aimed to conduct a comprehensive systematic review and meta-analysis to systematically evaluate and quantitatively compare survival outcomes, 30-day postoperative mortality, and baseline characteristics between patients undergoing P/D and EPP for PM. Methods: A systematic review was conducted in accordance with the PRISMA guidelines. MEDLINE, Embase, and Scopus were searched up to May 2025. Studies comparing EPP and P/D in PM that reported on survival, mortality, or baseline demographics were included. Data from 24 retrospective studies were extracted. Pooled estimates were calculated using random-effects models. Meta-regression and subgroup analyses were performed by geographic region and publication year. Results: P/D was associated with a significantly improved overall survival compared to EPP in the primary analysis (mean difference = 7.01 months; 95% CI: 1.15-12.86; p = 0.018), with substantial heterogeneity (I2 = 98.5%). In a sensitivity analysis excluding one statistical outlier, the survival benefit remained significant (mean difference = 4.31 months; 95% CI: 1.69-6.93), and heterogeneity was markedly reduced. The 30-day mortality rate was also significantly lower for P/D (odds ratio = 0.34; 95% CI: 0.13-0.88; p = 0.027). Patients undergoing P/D were, on average, 3.78 years older than those undergoing EPP (p < 0.001), whereas no significant difference was observed in the sex distribution between groups. Subgroup analyses by region and publication year confirmed the robustness of the findings. Meta-regression did not reveal substantial modifiers of survival. Conclusions: P/D demonstrates superior overall survival and reduced perioperative mortality compared to EPP, without evidence of baseline demographic confounding. These findings, derived from retrospective comparative studies, support the preferential use of P/D in eligible patients, particularly in high-volume centers, given its favorable safety profile and superior median survival. However, the absence of randomized trials directly comparing P/D and EPP and the potential influence of patient selection warrant cautious interpretation, and surgical decisions should be tailored to individual patient factors within a multidisciplinary setting.
Prognostic Value of Chest CT Volumetric Analysis in Patients with Malignant Pleural Mesothelioma. E. Baratella, E. Ercolani, A. Segalotti, et al. 2025;14(5). PubMed · Publisher · Free full text

Abstract

Background/Objectives: Malignant pleural mesothelioma (MPM) is a rare, aggressive cancer linked to asbestos exposure and with poor overall survival. In recent years, CT volumetric analysis has gained increasing interest as a more accurate method for assessing tumor burden. This study aims to evaluate the prognostic value of chest CT volumetric analysis in MPM, comparing tumor volume with tumor thickness measurements and survival outcomes. Methods: This is a retrospective, observational analysis of all patients undergoing diagnostic thoracoscopy between 2014 and 2021 at the University Hospital of Cattinara (Trieste, Italy). Inclusion criteria were as follows: age ≥ 18 years, histological diagnosis of MPM, and the availability of at least one contrast-enhanced chest CT scan at the time of diagnosis. For each patient, the tumor thickness was measured on the axial plane at three levels (upper, middle, and lower hemithorax). Tumor and effusion volumes were calculated with the RayStation® software version 11.7.174 (HealthMyne®, Madison, WI, USA). Results: A total of 81 patients were eligible for analysis. Maximum and mean tumor thickness were strongly associated with survival, with higher thicknesses correlating with an increased risk of death (adjusted hazard ratio per doubling (aHR) of 1.97 (95%CI: 1.40-2.77) and of 2.23 (95%CI: 1.56-3.20), p < 0.001)), respectively, while the effect of the tumor volume on survival was nevertheless significant but less impactful (aHR = 1.26 (1.10-1.45, p < 0.001)). The presence and volume of effusion did not correlate with survival (p = 0.48 and p = 0.64, respectively). Conclusions: This study supports the role of quantitative parameters for staging MPM, particularly given the frequent discrepancies between clinical and pathological staging when relying solely on qualitative measures.
The Accuracy of Video-Assisted Thoracic Surgery Pleural Biopsy in Patients with Suspected Diffuse Pleural Mesothelioma: A Real-Life Study. L. Balsamo, E. Migliore, E. Della Beffa, et al. 2025;15(1). PubMed · Publisher · Free full text

Abstract

Background: The heritage of occupational and environmental asbestos exposure in Piedmont, Italy, has resulted in an enduring diffuse pleural mesothelioma (DPM) epidemic. Our study aimed to investigate the accuracy of Pleural biopsy (PB) via thoracoscopy (or video-assisted thoracic surgery-VATS) and analyze the diagnostic path of patients who experienced an initial DPM misdiagnosis. Methods: Patients who underwent PB by VATS for suspected DPM from 2004 to 2013 were analyzed. The Registry of Malignant Mesothelioma (RMM) records were examined to cross-check incident cases and identify misdiagnosed DPM. The sensitivity and specificity of the initial PB assessment versus the final classification of cases by RMM were evaluated. Results: Data from 552 patients were analyzed, and DPM was diagnosed in 178 cases (32%). Sensitivity and specificity were 93% and 100%, respectively. The number of false-negative PBs was 14 (2%). Of those, 10 (71%) had an initial diagnosis of chronic pleuritis, 3 (28.5%) were initially classified as mesothelial proliferation, and 1 had reactive mesothelial proliferation. All of them reported a history of asbestos exposure, and the correct diagnosis was reached after a median of 160 days. One- and four-year survival rates were 52% and 10% in DPM PB-positive cases and 50% and 19% in false-negative cases. Conclusions: When a strong clinical suspicion after a negative PB remains, iterative biopsy attempts should be considered, especially if a history of asbestos exposure is reported. In high-volume centers, the DPM misdiagnosis rate remains low, and future advancements in diagnostic technologies could further increase the accuracy and efficacy of histologic diagnosis.
The Effect of Splenectomy on Postoperative Morbidity and Survival in Patients with Peritoneal Carcinomatosis. S. Ademoğlu, İ.C. Aydın, A.O. Sunar, et al. 2025;14(22). PubMed · Publisher · Free full text

Abstract

Background/Objectives: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are effective treatment modalities for patients with peritoneal carcinomatosis (PC), though splenectomy is frequently required and its impact on outcomes remains unclear. Previous studies have evaluated splenectomy as a binary variable without distinguishing surgical indication, potentially obscuring important prognostic differences. This retrospective study aimed to evaluate the impact of splenectomy on postoperative morbidity and survival in patients undergoing CRS + HIPEC. Methods: A retrospective analysis was conducted on 149 patients who underwent CRS + HIPEC between 2018-2022 at a single tertiary center. The study examined patients with various cancer origins, including colorectal, ovarian, gastric, pseudomyxoma peritonei, and malignant peritoneal mesothelioma. Demographic characteristics, surgical procedures, complications, and survival outcomes were comprehensively analyzed. Patients were categorized by splenectomy and further stratified by surgical indication (iatrogenic injury, peritoneal implants, hilar tumor invasion). Results: Splenectomy was associated with longer ICU stay (median 1.5 vs. 1 day, p < 0.001) and hospitalization (median 12 vs. 9 days, p = 0.005). Individual pulmonary complications were more frequent in the splenectomy group, though major complication rates (Clavien-Dindo ≥ 3) were similar (34.7% vs. 21.7%, p = 0.086). When analyzed without stratification by indication, splenectomy showed no impact on OS (median 42.7 vs. 42.2 months, p = 0.665) or DFS (median 32.1 vs. 35.4 months, p = 0.138). However, stratification by indication revealed divergent prognostic effects: splenectomy for peritoneal implants independently predicted worse DFS (OR = 17.814, 95% CI: 3.025-104.894, p = 0.001), while splenectomy for hilar invasion was protective (OR = 0.136, 95% CI: 0.025-0.736, p = 0.021). PCI independently predicted both OS (OR = 1.150 per point, p = 0.006) and DFS (OR = 1.166 per point, p < 0.001). Primary tumor type was not independently prognostic after adjusting for PCI (OS p = 0.345, DFS p = 0.163). Conclusions: Splenectomy during CRS + HIPEC was associated with prolonged intensive care and hospital stays without increasing major complications. Peritoneal implant-related splenectomy predicts worse DFS, likely reflecting extensive disease burden, while hilar invasion-related splenectomy is protective, possibly reflecting more complete regional clearance achieved during en bloc resection to attain CC-0. Given the retrospective nature of this study and the heterogeneous patient population, these findings should be interpreted with caution. Further prospective research with larger, more homogeneous patient cohorts is warranted to definitively establish the long-term implications of splenectomy in CRS + HIPEC procedures.
Diagnostic Accuracy of Ultrasound Guided Percutaneous Pleural Needle Biopsy for Malignant Pleural Mesothelioma. C. Iadevaia, V. D'Agnano, R. Pagliaro, et al. 2024;13(9). PubMed · Publisher · Free full text

Abstract

Background/Objectives: Ultrasound (US) has been progressively spreading as the most useful technique for guiding biopsies and fine-needle aspirations that are performed percutaneously. Malignant pleural mesothelioma (MPM) represents the most common malignant pleural tumour. Thoracoscopy represents the gold standard for diagnosis, although conditions hampering such diagnostic approach often coexist. The Objective was to determine whether ultrasound-guided percutaneous needle biopsy (US-PPNB) has a high diagnostic accuracy and represents a safe option for diagnosis of MPM. Methods: US-PPNB of pleural lesions suspected for MPM in patients admitted from January 2021 to June 2023 have been retrospectively analyzed. An 18-gauge semi-automatic spring-loaded biopsy system (Medax Velox 2®) was used by experienced pneumologists. The obtained specimens were histologically evaluated and defined as adequate or non-adequate for diagnosis according to whether the material was considered appropriate or not for immunohistochemistry (IHC) analysis. The primary objective of the study was the diagnostic yield for a tissue diagnosis. Results: US-PPNB was diagnostic of MPM in 15 out of 18 patients (sensitivity: 83.39%; specificity: 100%; PPV: 100%). Three patients with non-adequate US-PPNB underwent thoracoscopy for diagnosis. We found significant differences in terms of mean pleural lesion thickness between patients with adequate and not-adequate biopsy (15.4 mm (SD: 9.19 mm) and 3.77 mm (SD: 0.60 mm), p < 0.0010. In addition, a significant positive correlation has been observed between diagnostic accuracy and FDG-PET avidity value. Conclusions: US-PPNB performed by a pneumologist represents a valid procedure with a high diagnostic yield and accuracy for the diagnosis of MPM, and may be considered as an alternative option in patients who are not suitable for thoracoscopy.
Malignant Pleural Mesothelioma: A Comprehensive Review. M. Jain, M.K. Crites, P. Rich, et al. 2024;13(19). Review PubMed · Publisher · Free full text

Abstract

Mesotheliomas are hyperplastic tumors that envelop the serosal membranes that safeguard the body's external surfaces. Although certain instances may exhibit indolent characteristics, a significant number of tumors demonstrate rapid progression and a poor prognosis. Mesotheliomas are typically categorized as benign or malignant, with malignant mesothelioma being more frequently linked to asbestos exposure. Malignant pleural mesothelioma (MPM) predominantly impacts males and often emerges in the late 50 s or beyond, characterized by a median age of early 70 s among patients exposed to asbestos lasting from 2 to 4 decades. Respiratory exposure to asbestos particles leads to the development of malignant mesothelioma, characterized by recurrent inflammation, disruption of cell division, activation of proto-oncogenes, and generation of free radicals. In pleural mesothelioma, BAP1, CDKN2A, and NF are the most often mutated genes. Accurate diagnosis and assessment usually require the use of chest computed tomography (CT) scans, magnetic resonance imaging (MRI), and positron emission tomography (PET). Radiation therapy, immunotherapy, chemotherapy, and surgery are some of the treatment options that are currently available. This systematic review provides a comprehensive analysis of the latest research, biomarkers, evaluation, and management strategies for malignant pleural mesothelioma.
Prognostic Value of PD-L1, BAP-1 and ILK in Pleural Mesothelioma. O. Illini, M. Benej, A.S. Lang-Stöberl, et al. 2024;13(23). PubMed · Publisher · Free full text

Abstract

Background: Pleural mesothelioma (PM) is a rare type of cancer with poor prognosis. Prognostic and predictive biomarkers could improve treatment strategies in these patients. Programmed death ligand 1 (PD-L1), integrin-linked kinase (ILK) and breast cancer gene 1-associated protein (BAP-1) have been proposed to predict outcomes in PM, but existing data are limited and controversial. Design and Methods: This single-center, retrospective study analyzed data on expression patterns and the prognostic role of PD-L1, ILK and BAP-1 in consecutive patients diagnosed with PM. Results: Of all patients (n = 52) included, more than half showed a positive PD-L1 expression (52% TPS ≥ 1%, 65% CPS ≥ 1), 69% showed a BAP-1 loss and 80% an ILK ≥ 50%. Positive PD-L1 expression was more frequent in the non-epithelioid subtype (p = 0.045). ILK intensity (p = 0.032) and positive PD-L1 (p = 0.034) were associated with more advanced tumor stages. The median overall survival (OS) was 16.9 (95% CI 13.1-25.2) months. Multimodality therapy (MMT) including surgery and early stage were independent prognostic factors for longer OS (MMT: HR 0.347, 95% CI 0.13-0.90, p = 0.029; advanced stage: HR 4.989; 95% CI 1.64-15.13, p = 0.005). Patients with an expression of PD-L1 TPS ≥ 1% or BAP-1 positivity showed numerically worse survival with a median OS of 15.3 (11.5; 24.4) vs. 20.0 (11.2; 34.9) and 11.3 (5.6; 31.0) vs. 20.0 (15.2; 28.1) months, respectively. Furthermore, PD-L1 was associated with worse survival in patients receiving MMT (PD-L1 TPS ≥ 1%: 15.8 (12.1-25.4) vs. 31.3 (17.4-95.4) p = 0.053). ILK expression ≥50% did not influence survival. The combinations of CPS ≥ 1% with BAP-1 positivity or ILK expression ≥50% were associated with worse survival (p = 0.045, p = 0.019). Conclusions: In this real-world analysis, expressions of PD-L1 and BAP-1 were associated with worse survival in patients with PM. ILK showed no prognostic value. Further studies with larger cohorts are needed to identify prognostic and predictive biomarkers facilitating optimized individual treatment decision in this rare type of cancer.
Immunotherapy vs. Chemotherapy in Subsequent Treatment of Malignant Pleural Mesothelioma: Which Is Better?. X. Guo, L. Lin, J. Zhu. 2023;12(7). Review PubMed · Publisher · Free full text

Abstract

(1) Background: Malignant pleural mesothelioma (MPM) is a rare but aggressive tumor arising from the pleural surface. For relapsed MPM, there is no accepted standard of- are for subsequent treatment. Thus, we aimed to compare the efficacy of chemotherapy, targeting drugs, and immune-checkpoint inhibitors (ICIs) as subsequent therapy for relapsed MPM. (2) Methods: The study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We searched several acknowledged databases. Primary outcomes were defined as overall median progressive survival (mPFS) and median overall survival (mOS) in different treatment groups. Secondary outcomes were defined as objective response rate (ORR), the proportion of stable disease (SD), and progressive disease (PD). (3) Results: Ultimately, 43 articles were selected for the meta-analysis. According to the results of a pooled analysis of single-arm studies, ICIs showed a slight advantage in mOS, while chemotherapy showed a slight advantage in mPFS (mOS: 11.2 m vs. 10.39 m and mPFS: 4.42 m vs. 5.08 m for ICIs group and chemotherapy group, respectively). We identified only a few studies that directly compared the efficacy of ICIs with that of chemotherapy, and ICIs did not show significant benefits over chemotherapy based on mOS. (4) Conclusions: Based on current evidence, we considered that immunotherapy might not be superior to chemotherapy as a subsequent therapy for relapsed MPM. Although several studies investigated the efficacy of ICIs, targeting drugs, and chemotherapy in relapsed MPM, there was still no standard of care. Further randomized control trials with consistent criteria and outcomes are recommended to guide subsequent therapy in relapsed MPM and identify patients with certain characteristics that might benefit from such subsequent therapy.
Peritoneal Mesothelioma in a High Volume Peritoneal Surface Malignancies Unit. F. Pereira, M. Pereira, I. Manzanedo, et al. 2023;12(6). PubMed · Publisher · Free full text

Abstract

Diffuse malignant peritoneal mesothelioma (PM) is a rare neoplasm, traditionally associated with a poor prognosis. There are other varieties of PM that are even less frequent and of uncertain malignancy. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has achieved prolonged survival in selected patients. The aim of this study is to analyze the patients with PM assessed in our center. Clinicopathological characteristics, diagnostic procedures and survival results from patients with PM appraised at our unit, according to the applied treatment, were analyzed. Seventeen patients were assessed between 2007 and 2019. Three cases had multicystic PM that were treated with complete CRS + HIPEC; all patients are alive and free of disease after a long follow-up. Three other cases had biphasic PM; a curative treatment could be performed in none of them, and their survival was minimal (<6 moths). Lastly, 11 cases with epithelioid PM were treated. Two cases were considered unresectable at laparoscopy (PCI 39); one of them had a long survival (67 months) with three iterative laparoscopic palliatives HIPECs for refractory ascites. The other nine cases were treated with curative CRS + HIPEC, with a median PCI of 14 (range 4-25), and a median overall survival (OS) of 58 months, with a 5-year OS of 47.4%. In conclusion, CRS + HIPEC, when possible, appears to be the optimal treatment for patients with PM. Knowledge of this therapeutic option is crucial, both to offer it to patients and to avoid delays in their referral to appropriate centers for treatment.
Peritoneal Metastases: Evolution from a Dark Horizon to an Encouraging Present and a Promising Future. M. Diez-Alonso, A. San-Juan, M.A. Ortega, et al. 2023;12(24). Editorial PubMed · Publisher · Free full text

Abstract

Peritoneal metastasis (PM) is the primary pattern of metastasis for primary tumours of the appendix, ovary, and peritoneal mesothelioma [...].
Pleural Mesothelioma: Advances in Blood and Pleural Biomarkers. C. Sorino, M. Mondoni, G. Marchetti, et al. 2023;12(22). Review PubMed · Publisher · Free full text

Abstract

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.
The Evolving Role of Immune-Checkpoint Inhibitors in Malignant Pleural Mesothelioma. M. Borgeaud, F. Kim, A. Friedlaender, et al. 2023;12(5). Review PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is a rare cancer usually caused by asbestos exposure and associated with a very poor prognosis. After more than a decade without new therapeutic options, immune checkpoint inhibitors (ICIs) demonstrated superiority over standard chemotherapy, with improved overall survival in the first and later-line settings. However, a significant proportion of patients still do not derive benefit from ICIs, highlighting the need for new treatment strategies and predictive biomarkers of response. Combinations with chemo-immunotherapy or ICIs and anti-VEGF are currently being evaluated in clinical trials and might change the standard of care in the near future. Alternatively, some non-ICI immunotherapeutic approaches, such as mesothelin targeted CAR-T cells or denditric-cells vaccines, have shown promising results in early phases of trials and are still in development. Finally, immunotherapy with ICIs is also being evaluated in the peri-operative setting, in the minority of patients presenting with resectable disease. The goal of this review is to discuss the current role of immunotherapy in the management of malignant pleural mesothelioma, as well as promising future therapeutic directions.
Treatment of Peritoneal Surface Malignancies by Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Spain: Results of the National Registry of the Spanish Group of Peritoneal Oncologic Surgery (REGECOP). I. Manzanedo, F. Pereira, P. Cascales-Campos, et al. 2023;12(11). PubMed · Publisher · Free full text

Abstract

Introduction: Treatment of Peritoneal Surface Malignancies (PSM) with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has achieved results never seen before in these patients, which classically have a poor prognosis. The possibility of conducting clinical trials in these diseases is complicated, since some of them are rare, so the analysis of large databases provides very valuable scientific information. The aim of this study is to analyze the global results of the National Registry of the Spanish Group of Peritoneal Oncologic Surgery (REGECOP), whose objective is to register all patients scheduled for HIPEC nationwide.

Methods: This is a retrospective analysis of the data recorded in the REGECOP from 36 Spanish hospitals from 2001 to 2021. There were 4159 surgical interventions in 3980 patients.

Results: 66% are women and 34% are men with a median age of 59 years (range 17-86). 41.5% of the patients were treated for Peritoneal Metastases (PM) of colorectal cancer (CRC); 32.4% were women with ovarian cancer (OC) with PM; 12.8% were treated for pseudomyxoma peritonei (PMP); 6.2% had PM from gastric cancer (GC); 4.9% had PM of non-conventional origin; and, finally, 2.1% of cases were patients diagnosed with peritoneal mesothelioma. The median Peritoneal Cancer Index (PCI) was 9 (0-39), and complete cytoreduction was achieved in 81.7% of the procedures. Severe morbidity (Dindo-Clavien grade III-IV) was observed in 17.7% of surgeries, with 2.1% mortality. Median hospital stay was 11 days (0-259). Median overall survival (OS) was 41 months for CRC patients, 55 months for women with OC, was not reached in PMP patients, was 14 months for GC patients, and 66 months in mesothelioma patients.

Conclusions: large databases provide extremely useful data. CRS with HIPEC in referral centers is a safe treatment with encouraging oncologic results in PSM.
Bereaved Family Members' Perspectives of Good Death and Quality of End-of-Life Care for Malignant Pleural Mesothelioma Patients: A Cross-Sectional Study. Y. Nagamatsu, Y. Sakyo, E. Barroga, et al. 2022;11(9). PubMed · Publisher · Free full text

Abstract

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.
Depression and Complicated Grief, and Associated Factors, of Bereaved Family Members of Patients Who Died of Malignant Pleural Mesothelioma in Japan. Y. Nagamatsu, Y. Sakyo, E. Barroga, et al. 2022;11(12). PubMed · Publisher · Free full text

Abstract

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.
Informative Power Evaluation of Clinical Parameters to Predict Initial Therapeutic Response in Patients with Advanced Pleural Mesothelioma: A Machine Learning Approach. R. Massafra, A. Catino, P.M.S. Perrotti, et al. 2022;11(6). PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is a rare neoplasm whose early diagnosis is challenging and systemic treatments are generally administered as first line in the advanced disease stage. The initial clinical response may represent a useful parameter in terms of identifying patients with a better long-term outcome. In this report, the initial therapeutical response in 46 patients affected with advanced/unresectable pleural mesothelioma was investigated. The initial therapeutic response was assessed by CT scan and clinical examination after 2-3 treatment cycles. Our preliminary evaluation shows that the group of patients treated with regimens including antiangiogenetics and/or immunotherapy had a significantly better initial response as compared to patients only treated with standard chemotherapy, exhibiting a disease control rate (DCR) of 100% (95% IC, 79.40-100%) and 80.0% (95% IC, 61.40-92.30%), respectively. Furthermore, the therapeutic response was correlated with the disease stage, blood leukocytes and neutrophils, high albumin serum levels, and basal body mass index (BMI). Specifically, the patients with disease stage III showed a DCR of 95.7% (95% IC, 78.1-99.9%), whereas for disease stage IV the DCR decreased to 66.7% (95% IC, 34.9-9.1%). Moreover, a better initial response was observed in patients with a higher BMI, who reached a DCR of 96.10% (95% IC, 80.36-99.90%). Furthermore, in order to evaluate in the predictive power of the collected features a multivariate way, we report the preliminary results of a machine learning model for predicting the initial therapeutic response. We trained a state-of-the-art algorithm combined to a sequential forward feature selection procedure. The model reached a median AUC value, accuracy, sensitivity, and specificity of 77.0%, 75%, 74.8%, and 83.3%, respectively. The features with greater informational power were gender, histotype, BMI, smoking habits, packs/year, and disease stage. Our preliminary data support the possible favorable correlation between innovative treatments and therapeutic response in patients with unresectable/advanced pleural mesothelioma. The small sample size does not allow concrete conclusions to be drawn; nevertheless, this work is the basis of an ongoing study that will also involve radiomics in a larger dataset.
Multifactorial Evaluation following Cytoreductive Surgery for Malignant Pleural Mesothelioma in Patients with High Symptom-Burden. R. Tajè, R. Fiorito, A. Patirelis, et al. 2022;11(21). PubMed · Publisher · Free full text

Abstract

Mesothelioma has a scant prognosis and a great impact on symptoms and the quality of life. Pleurectomy/decortication and extrapleural pneumonectomy are the two cytoreductive surgical strategies, with different invasiveness, but achieving similar oncological results. Hereafter, the two surgical procedures effects on symptoms and the quality of life are compared in a high symptom-burden population. Between 2003 and 2017, 55 consecutive patients underwent pleurectomy/decortication (n = 26) or extrapleural pneumonectomy (n = 29), both followed by adjuvant chemo-radiotherapy. Cardio-pulmonary function, symptoms and the quality of life (Short-Form-36 and St.George's questionnaires) were evaluated pre- and 3-, 6-, 12- and 24-months postoperatively. Extrapleural pneumonectomy demonstrated lower pain at 12 months but a higher decrement of forced vital capacity at 24 months than pleurectomy/decortication. Both procedures revealed a 3-months improvement of many symptoms and the quality of life determinants. Improvement in physical, social and pain-related measured parameters lasted for a longer time-spawn in the extrapleural pneumonectomy group. No differences were found in chemotherapy compliance and survival between groups. Age-at-presentation (p = 0.02) and non-epitheliod histology (p = 0.10) were the only significant prognosticators. Surgery, despite poor survival results, improved symptoms and the quality of life in patients with mesothelioma with high symptom-burden at diagnosis. Therefore, extrapleural pneumonectomy demonstrated the most durable effects.
Radiation-Induced Lung Injury: Prevention, Diagnostics and Therapy in the Era of the COVID-19 Pandemic. L. Käsmann, J. Taugner, A. Nieto, et al. 2022;11(19). Editorial PubMed · Publisher · Free full text

Abstract

Thoracic radiotherapy (TRT) plays an integral role in the multimodal treatment of lung cancer, breast cancer, esophageal cancer, thymoma and mesothelioma, having been used as either a definitive, neoadjuvant or adjuvant treatment or for palliative intention to achieve symptom control [...].
Second Surgery for Recurrent Malignant Pleural Mesothelioma after Multimodality Treatment: A Systematic Review. A. Bellini, S. Mazzarra, S. Sterrantino, et al. 2022;11(12). Review PubMed · Publisher · Free full text

Abstract

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.
Single-Center 20-Year Experience in Surgical Treatment of Malignant Pleural Mesothelioma. G. Mangiameli, E. Bottoni, U. Cariboni, et al. 2022;11(15). PubMed · Publisher · Free full text

Abstract

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).
Sneaky Diagnosis of Pleural Malignant Mesothelioma in Thoracic Surgery: All That Glitters Is Not Gold. R. Orlandi, F. Bono, D.L. Cortinovis, et al. 2022;11(11). PubMed · Publisher · Free full text

Abstract

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.
Systematic Review and Meta-Analysis of Pleurectomy/Decortication versus Extrapleural Pneumonectomy in the Treatment of Malignant Pleural Mesothelioma. F. Danuzzo, S. Maiorca, G. Bonitta, et al. 2022;11(19). Review PubMed · Publisher · Free full text

Abstract

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 = <0.01), whereas only five studies reported 90-day mortality, and no statistically significant difference between EPP and P/D was found (RR = 0.71; 95% CI from 0.47 to 1.07; 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.
The Effects of Preserving the Diaphragm on Early and Late Outcome of Lung-Sparing Radical Surgery for Malignant Pleural Mesothelioma. M. Lee, L. Ventura, R. Baranowski, et al. 2022;11(22). PubMed · Publisher · Free full text

Abstract

Background: The accepted aim of radical surgery for malignant pleural mesothelioma (MPM) is the achievement of macroscopic complete resection (MCR) whilst reducing perioperative morbidity by preserving normal tissue. Whilst preservation of the lung by pleurectomy/decortication (PD) has become widely utilised, there remains debate regarding the management of the diaphragm. Muscle-sparing complete excision of the diaphragmatic pleura is technically challenging; thus, surgeons may proceed to extended PD with phrenectomy and possible increased morbidity or to preserve the diaphragmatic pleura at the expense of MCR with potential survival deficit. We aimed to evaluate the effects of an intentional change in protocol to diaphragm-sparing PD whilst maintaining MCR as the treatment of choice for MPM.

Methods: In a series of 136 patients (111M:25F, median age 68(63-73) years) undergoing radical surgery for MPM, we identified 28 patients (22M:6F, median age 67(60-71) years) in whom MCR was achieved without phrenectomy (PD group). We compared their perioperative outcomes and survival with a historical control group of 18 patients (18M:0F, median age 69(57-78) years) in whom MCR had been achieved with phrenectomy (EPD group) but in whom there was no histological evidence of diaphragm muscle invasion and who, in retrospect, could have undergone muscle-sparing MCR if this procedure had been attempted.

Results: There was no significant intergroup difference in demographics or tumour cell type; the majority of both groups were found to be epithelial (PD 85.7%, EPD 77.8%). The EPD group was found to be more locally advanced (T3 55.56%) than the PD group (T1 46.43%) (p = 0.03). All the following parameters were significantly reduced after PD compared to EPD: operative time (188 vs. 220 min, p = 0.007); duration of air leak (5 vs. 10 days, p = 0.001), duration of inotrope (p = 0.009) and post-operative hospital stay (8 vs. 13 days, p = 0.034). There were no significant differences (p = 0.123) in overall survival (OS) between the two groups, but the median survival in the PD group had not been reached at a median follow up of 33.9 (24.2-46) months.

Conclusions: A surgical strategy of attempting to spare the diaphragm whilst still achieving MCR wherever possible is justified by improved perioperative outcomes without compromising OS.
Treatment of Patients with Malignant Peritoneal Mesothelioma. C.Y. Li, T. Kennedy, H.R. Alexander. 2022;11(7). Review PubMed · Publisher · Free full text

Abstract

Malignant peritoneal mesothelioma is a rare malignancy arising from the serosa of the peritoneal cavity. It is diagnosed based on suspicious findings on cross sectional imaging and a tissue biopsy showing confirmatory histologic and immunohistochemical features. The disease is hallmarked by its propensity to progress mainly in the peritoneal cavity. In selected patients, surgical cytoreduction and hyperthermic intra-operative peritoneal chemotherapy has become the initial preferred treatment and is associated with provide prolonged in many patients. Systemic chemotherapy using a couplet of cisplatin or gemcitabine with pemetrexed has modest response rates and duration of response. Expression of PD-L1 has been demonstrated in peritoneal mesothelioma tumors and there has been significant interest in the use of check point blockade targeted against PD-L1 in this clinical setting. Future clinical research using a combination of check point blockade with surgical cytoreduction is a high clinical priority.
Computed Tomography and Spirometry Can Predict Unresectability in Malignant Pleural Mesothelioma. A. Bellini, A. Dell'Amore, C. Giraudo, et al. 2021;10(19). PubMed · Publisher · Free full text

Abstract

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 <77.5% and >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.
Extended Pleurectomy/Decortication for Malignant Pleural Mesothelioma: Humanitas's Experience. G. Mangiameli, E. Bottoni, E. Voulaz, et al. 2021;10(21). PubMed · Publisher · Free full text

Abstract

Background: We analysed a series of malignant pleural mesothelioma (MPM) patients who consecutively underwent extended Pleurectomy/Decortication (eP/D) in a centre with a high level of thoracic surgery experience (IRCCS Humanitas Research Hospital) to explore postoperative morbidity and mortality, pattern of recurrence and survival.

Methods: A retrospective analysis was performed on MPM patients underwent eP/D in our centre from 2010 to 2021. All patients were identified from our departmental database. Postoperative complications were scored according to Clavien-Dindo criteria. Survival analysis was performed by the Kaplan-Meier methods and Cox multivariable analysis.

Results: Eighty-five patients underwent extended pleurectomy decortication (eP/D) during study period. Macroscopical residual disease (R2) was reported in one case. A neoadjuvant chemotherapy regiment was administrated in 88% of the surgical cohort. A complete trimodality treatment including induction with platinum agents and pemetrexed, radical cytoreductive surgery and volumetric modulated arc therapy technology (VMAT) could be administered in 63 patients (74%). Postoperative morbidity rate was 54.11%, major complications (defined as Clavien-Dindo ≥ 3) were reported in 11 patients (12.9%). Thirty-day mortality and 90-day mortality were, respectively, 2.35% and 3.53%. Median disease-free and overall survival were, respectively, 13.7 and 25.5 months. The occurrence of major complications (Clavien-Dindo ≥ 3), operative time, pT3-T4, pathological node involvement (pN+) were prognostic factors associated with worse survival.

Conclusions: In our experience, eP/D is a well-tolerated procedure with acceptable mortality and morbidity, allowing for the administration of trimodality regimens in most patients. eP/D offered in a multimodality treatment setting have satisfactory long term oncological results. To obtain best oncological results the goal of surgery should be macroscopic complete resection in carefully selected patients (clinical N0).
Hyperthermic Intrathoracic Chemotherapy for Malignant Pleural Mesothelioma: The Forefront of Surgery-Based Multimodality Treatment. V. Aprile, A. Lenzini, F. Lococo, et al. 2021;10(17). Review PubMed · Publisher · Free full text

Abstract

Introduction: Malignant Pleural Mesothelioma (MPM) is characterized by an aggressive behavior and an inevitably fatal prognosis, whose treatment is still far from being standardized. The role of surgery is questionable since a radical resection is unattainable in most cases. Hyperthermic IntraTHOracic Chemotherapy (HITHOC) combines the advantages of antitumoral effects together with those of high temperature on the exposed tissues with the aim to improve surgical radicality.

Material And Methods: this is a narrative review on the role of HITHOC in the management of MPM patients. To provide data on the beginnings and the historical evolution of this technique, we searched the available literature by selecting the more exhaustive papers on this topic.

Results: from 1994 to date different authors experimented HITHOC following a cytoreductive surgery in MPM, obtaining in most cases a good local control and a better overall survival associated to very low complication rate.

Conclusions: HITHOC may be considered as a safe, feasible and effective procedure although there is a high heterogeneity between different protocols adopted worldwide. More structured studies are needed to reach a unanimous consensus on this technique.
Induction Chemotherapy Followed by Pleurectomy Decortication and Hyperthermic Intraoperative Chemotherapy (HITHOC) for Early-Stage Epitheliod Malignant Pleural Mesothelioma-A Prospective Report. S. Bongiolatti, F. Mazzoni, O. Salimbene, et al. 2021;10(23). PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is an aggressive disease with poor prognosis and the current treatment for early-stage MPM is based on a multimodality therapy regimen involving platinum-based chemotherapy preceding or following surgery. To enhance the cytoreductive role of surgery, some peri- or intra-operative intracavitary treatments have been developed, such as hyperthermic chemotherapy, but long-term results are weak. The aim of this study was to report the post-operative results and mid-term outcomes of our multimodal intention-to-treat pathway, including induction chemotherapy, followed by surgery and Hyperthermic Intraoperative THOracic Chemotherapy (HITHOC) in the treatment of early-stage epithelioid MPM. Since 2017, stage I or II epithelioid MPM patients have been inserted in a surgery-based multimodal approach comprising platinum-based induction chemotherapy, followed by pleurectomy and decortication (P/D) and HITHOC with cisplatin. The Kaplan-Meier method was used to estimate overall survival (OS), disease-free survival (DFS) and progression-free survival (PFS). During the study period, n = 65 patients affected by MPM were evaluated by our institutional Multidisciplinary Tumour Board; n = 12 patients with stage I-II who had no progression after induction chemotherapy underwent P/D and HITHOC. Post-operative mortality was 0, and complications developed in n = 7 (58.3%) patients. The median estimated OS was 31 months with a 1-year and 3-year OS of 100% and 55%, respectively. The median PFS was 26 months with 92% of a 1-year PFS, whereas DFS was 19 months with a 1-year DFS rate of 83%. The multimodal treatment of early-stage epithelioid MPM, including induction chemotherapy followed by P/D and HITHOC, was well tolerated and feasible with promising mid-term oncological results.
Interstitial Lung Abnormalities Detected by CT in Asbestos-Exposed Subjects Are More Likely Associated to Age. F. Laurent, I. Benlala, G. Dournes, et al. 2021;10(14). PubMed · Publisher · Free full text

Abstract

Objective: the aim of this study was to evaluate the association between interstitial lung abnormalities, asbestos exposure and age in a population of retired workers previously occupationally exposed to asbestos.

Methods: previously occupationally exposed former workers to asbestos eligible for a survey conducted between 2003 and 2005 in four regions of France, underwent chest CT examinations and pulmonary function testing. Industrial hygienists evaluated asbestos exposure and calculated for each subject a cumulative exposure index (CEI) to asbestos. Smoking status information was also collected in this second round of screening. Expert radiologists performed blinded independent double reading of chest CT-scans and classified interstitial lung abnormalities into: no abnormality, minor interstitial findings, interstitial findings inconsistent with UIP, possible or definite UIP. In addition, emphysema was assessed visually (none, minor: emphysema <25%, moderate: between 25 and 50% and severe: >50% of the lung). Logistic regression models adjusted for age and smoking were used to assess the relationship between interstitial lung abnormalities and occupational asbestos exposure.

Results: the study population consisted of 2157 male subjects. Interstitial lung abnormalities were present in 365 (16.7%) and emphysema in 444 (20.4%). Significant positive association was found between definite or possible UIP pattern and age (OR adjusted =1.08 (95% CI: 1.02-1.13)). No association was found between interstitial abnormalities and CEI or the level of asbestos exposure.

Conclusion: presence of interstitial abnormalities at HRCT was associated to aging but not to cumulative exposure index in this cohort of former workers previously occupationally exposed to asbestos.
IRF3 Knockout Results in Partial or Complete Rejection of Murine Mesothelioma. M. Aoki, L. Wu, J. Murakami, et al. 2021;10(21). PubMed · Publisher · Free full text

Abstract

Background: Malignant pleural mesothelioma (MESO) has a poor prognosis despite aggressive treatment with surgery, radiation and chemotherapy, and novel therapeutic approaches are needed. IRF3 is a downstream molecule of the cGAS/STING signaling pathway, but its roles have not been investigated in MESO.

Methods: Various murine mesothelioma cell lines were inoculated into wild type (WT) and IRF3 knockout (IRF3KO) mice to compare tumor growth. AE17-bearing mice were treated with local radiotherapy (LRT) to evaluate the effect on tumor growth, and immune cell infiltration was analyzed by flow cytometry 20 days after tumor inoculation. TCGA data were used to examine the relationship between mRNA expression of IRF3 and genes of the cGAS/STING signaling cascade on prognosis in MESO. Correlations between gene expression of IRF3, cGAS/STING signaling pathway, and immune checkpoints were analyzed in TCGA MESO and our scRNA-Seq data from MESO patients.

Results: In mouse mesothelioma models, AK7, RN5 and ZiP3 were completely rejected in IRF3KO mice 20 days after the tumor challenge. AE17tumor volume was slightly larger than WT mice around day 10 before shrinking and becoming significantly smaller than WT mice on day 20. LRT accelerated tumor shrinkage of AE17 tumors in IRF3KO mice. Compared with WT mice, the number of macrophages infiltrating the tumor of IRF3KO mice was significantly reduced, and CD4+ T cells and CD8+IFNγ+ T cells were significantly increased. TCGA data showed that IRF3 expression was an unfavorable prognostic factor in MESO patients. IRF3 expression, the cGAS/STING signaling pathway, and immune checkpoints were positively correlated.

Conclusion: IRF3 could play a critical role in the tumor immune microenvironment of MESO.
Malignant Pleural Mesothelioma Nodal Status: Where Are We at?. S. Ricciardi, F. Carleo, M.O. Jaus, et al. 2021;10(21). Review PubMed · Publisher · Free full text

Abstract

Due to the lack of both prospective trial and high-volume retrospective studies, the management of clinical N+ malignant pleural mesothelioma (MPM) patients remains highly debated. Node positive patients show poor survival compared with node-negative ones; thus, lymph node staging appears crucial in determining treatment strategy. Notwithstanding the improvement in pre-treatment staging and the update on lymph node classification in the 8th edition of TNM, several open controversies remain on N parameter. How should we stage suspected N+ patients? How should we treat node positive patients? Which is the definition of a "resectable patient"? Is the site or the number the main prognostic factor for node positive patients? The aim of our narrative review is to analyse the existing relevant literature on lymph node status in MPM.
Malignant Pleural Mesothelioma: Time Is Running Out. F. Lococo. 2021;10(4). Editorial PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is a rare but highly malignant disease of the pleura usually related to asbestos exposure [...].
Management of Pleural Effusion Secondary to Malignant Mesothelioma. V. Musso, C. Diotti, A. Palleschi, et al. 2021;10(18). Review PubMed · Publisher · Free full text

Abstract

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.
Molecular Fingerprints of Malignant Pleural Mesothelioma: Not Just a Matter of Genetic Alterations. E. Lorenzini, A. Ciarrocchi, F. Torricelli. 2021;10(11). Review PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is a clinical emergency of our time. Being strongly associated with asbestos exposure, incidence of this cancer is ramping up these days in many industrialized countries and it will soon start to increase in many developing areas where the use of this silicate derivate is still largely in use. Deficiency of reliable markers for the early identification of these tumors and the limited efficacy of the currently available therapeutic options are the basis of the impressive mortality rate of MPM. These shortcomings reflect the very poor information available about the molecular basis of this disease. Results of the recently released deep profiling studies point to the epigenome as a central element in MPM development and progression. First, MPM is characterized by a low mutational burden and a highly peculiar set of mutations that hits almost exclusively epigenetic keepers or proteins controlling chromatin organization and function. Furthermore, asbestos does not seem to be associated with a distinctive mutational signature, while the precise mapping of epigenetic changes caused by this carcinogen has been defined, suggesting that alterations in epigenetic features are the driving force in the development of this disease. Last but not least, consistent evidence also indicates that, in the setting of MPM, chromatin rewiring and epigenetic alterations of cancer cells heavily condition the microenvironment, including the immune response. In this review we aim to point to the relevance of the epigenome in MPM and to highlight the dependency of this tumor on chromatin organization and function. We also intend to discuss the opportunity of targeting these mechanisms as potential therapeutic options for MPM.
Oncological Frontiers in the Treatment of Malignant Pleural Mesothelioma. E. Vita, A. Stefani, M. Di Salvatore, et al. 2021;10(11). Review PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is a rare malignancy characterized by very poor prognosis and lack of treatment options. Immunotherapy has rapidly emerged as an effective tool for MPM, particularly for tumors of non-epithelioid histology. At the same time, comprehensive genomic sequencing may open the way to new-generation targeted-drugs able to hit specific MPM molecular vulnerabilities. These innovations will possibly enrich, but also dramatically complicate, the elucidation of treatment algorithms. Multidisciplinary integration is urgently needed.
Relapse Patterns and Tailored Treatment Strategies for Malignant Pleural Mesothelioma Recurrence after Multimodality Therapy. A. Bellini, A. Dell'Amore, S. Terzi, et al. 2021;10(5). PubMed · Publisher · Free full text

Abstract

To date, there have been no established therapies for recurrent malignant pleural mesothelioma (MPM) after multimodality treatment. Aims of this retrospective study are to analyze the recurrence pattern, its treatment and to identify the predictors of best oncological outcomes for relapsed MPM, comparing extrapleural pneumonectomy (EPP) vs. pleurectomy/decortication (PD). Study population: 94 patients with recurrence of MPM after multimodality treatment underwent macroscopic complete resection (52.1% with EPP and 47.9% with PD) between July 1994 and February 2020. Distant spread was the most frequent pattern of recurrence (71.3%), mostly in the EPP group, while the PD group showed a higher local-only failure rate. Post-recurrence treatment was administered in 86.2%, whereas best supportive care was administered in 13.8%. Median post-recurrence survival (PRS) was 12 months (EPP 14 vs. PD 8 months, p = 0.4338). At multivariate analysis, predictors of best PRS were epithelial histology (p = 0.026, HR 0.491, IC95% 0.263-0.916), local failure (p = 0.027, HR 0.707, IC95% 0.521-0.961), DFS ≥ 12 months (p = 0.006, HR 0.298, IC95% 0.137-0.812) and post-recurrence medical treatment (p = 0.046, HR 0.101, IC95% 0.897-0.936). The type of surgical intervention seems not to influence the PRS if patients are fit enough to face post-recurrence treatments. In patients with a prolonged disease-free interval, in the case of recurrence the most appropriate treatment seems to be the systemic medical therapy, even in the case of local-only relapse.
Serum Calretinin as a Biomarker in Malignant Mesothelioma. C. Zupanc, A. Franko, D. Štrbac, et al. 2021;10(21). PubMed · Publisher · Free full text

Abstract

The early diagnosis of malignant mesothelioma (MM) could improve the prognosis of MM patients. To confirm an MM diagnosis, an immunohistochemical analysis of several tumor tissue markers, including calretinin, is currently required. Our aim is to evaluate serum calretinin as a potential biomarker in asbestos-related diseases, especially in MM. Our study includes 549 subjects: 164 MM patients, 117 subjects with asbestosis, 195 subjects with pleural plaques and 73 occupationally asbestos-exposed subjects without asbestos-related diseases. The serum calretinin concentration was determined with a commercially available enzyme immunoassay. Data on the soluble mesothelin-related peptides (SMRP) concentration are available from previous studies. MM patients had a significantly higher calretinin concentration than subjects without disease, subjects with pleural plaques or subjects with asbestosis (all p < 0.001). The histological type was significantly associated with serum calretinin: patients with sarcomatoid MM had lower calretinin than patients with the epithelioid type (p = 0.001). In a ROC curve analysis, the area under the curve for calretinin concentration predicting MM was 0.826 (95% CI = 0.782-0.869; p < 0.001). At the cutoff value of 0.32 ng/mL, sensitivity was 0.683, while specificity was 0.886. The combination of calretinin and SMRP had the highest predictive value. Calretinin is a useful biomarker that can distinguish MM from other asbestos-related diseases and could, therefore, contribute to an earlier non-invasive diagnosis of MM.
Surgical Diagnosis of Malignant Pleural Mesothelioma: 20 Years' Experience at a High-Volume Referral Center. A. Iaffaldano, T. Charrier, F. Lococo, et al. 2021;10(9). PubMed · Publisher · Free full text

Abstract

Despite advances, malignant pleural mesothelioma (MPM) remains a challenging disease in terms of diagnosis, treatment, and overall management. Herein, we analyzed, in a large-scale single-center cohort, the characteristics and perioperative course of patients undergoing surgical diagnosis of MPM. We identified a total of 514 consecutive patients, 71.4% male and 28.6% female, with mean age 71.3 +/- 13.6 years. Most exhibited pleural, respiratory, or general symptoms and American Society of Anesthesiologists (ASA) score was ≥3 in 68.3% of cases. Thoracoscopy was the most frequent approach (92.0%) and short open thoracotomy was performed in the remaining patients. Pleurodesis was simultaneously performed in 74.3% of cases. Diagnostic failure led to redo surgery in 3.7% of patients. Non-epithelioid histology was found in 19.5% of MPMs and was significantly more frequent in right-sided MPM (p = 0.04), and in patients without history of cancer (p = 0.03), or pleural nodules at thoracoscopy (p = 0.01). Minor only or major complications occurred in respectively 7.8% and 3.6% of cases. They were more frequent in patients ≥ 70 years (p = 0.05) and Performance Status > 2 (p = 0.05). The mean hospital stay was 7.5 days. The 30-day and 90-day early mortality rates were 2.3% and 6.4%, respectively. Surgical diagnosis of MPM is a reliable procedure but is associated with significant morbidity and hospital-stay duration.
Surgical Management and Reconstruction of Diaphragm, Pericardium and Chest Wall in Mesothelioma Surgery: A Review. P. Bertoglio, E. Garelli, J. Brandolini, et al. 2021;10(11). Review PubMed · Publisher · Free full text

Abstract

Mesothelioma is an aggressive disease arising from parietal pleura. Surgery is a valuable option in the frame of a multimodality treatment. Several surgical approaches have been standardized with the aim of a macroscopic complete resection; these often require homolateral diaphragm and pericardial resection and reconstruction. Extrapleural pneumonectomy (EPP) and extended pleurectomy decortication (EPD) have been recognized as radical surgical procedures. Nevertheless, both operations are technically challenging and associated with a significant rate of peri-operative morbidity and non-negligible mortality. The diaphragmatic and pericardial reconstruction technique is mandatory to avoid respiratory impairment and to reduce post-operative complications like gastric and cardiac herniation. Moreover, in the case of localized chest wall recurrence, surgery might be considered a valuable therapeutical option for highly selected and fit patients. All the technical aspects of the resection and reconstruction of the diaphragm, pericardium, and chest wall are described as well as the possible use of new minimally invasive techniques. In addition, the choice of different prosthetic materials, considering the most recent innovations in the field, are discussed.
The Evolving Landscape of the Molecular Epidemiology of Malignant Pleural Mesothelioma. S. Lettieri, C. Bortolotto, F. Agustoni, et al. 2021;10(5). Review PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is a rare and aggressive malignancy that most commonly affects the pleural lining of the lungs. It has a strong association with exposure to biopersistent fibers, mainly asbestos (80% of cases) and-in specific geographic regions-erionite, zeolites, ophiolites, and fluoro-edenite. Individuals with a chronic exposure to asbestos generally have a long latency with no or few symptoms. Then, when patients do become symptomatic, they present with advanced disease and a worse overall survival (about 13/15 months). The fibers from industrial production not only pose a substantial risk to workers, but also to their relatives and to the surrounding community. Modern targeted therapies that have shown benefit in other human tumors have thus far failed in MPM. Overall, MPM has been listed as orphan disease by the European Union. However, molecular high-throughput profiling is currently unveiling novel biomarkers and actionable targets. We here discuss the natural evolution, mainly focusing on the novel concept of molecular epidemiology. The application of innovative endpoints, quantification of genetic damages, and definition of genetic susceptibility are reviewed, with the ultimate goal to point out new tools for screening of exposed subject and for designing more efficient diagnostic and therapeutic strategies.
The Prognostic Value of 18F-FDG PET Imaging at Staging in Patients with Malignant Pleural Mesothelioma: A Literature Review. S. Taralli, R.G. Giancipoli, C. Caldarella, et al. 2021;11(1). Review PubMed · Publisher · Free full text

Abstract

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.
When the Diagnosis of Mesothelioma Challenges Textbooks and Guidelines. G. Rossi, F. Davoli, V. Poletti, et al. 2021;10(11). Review PubMed · Publisher · Free full text

Abstract

The diagnosis of malignant mesothelioma (MPM) does not pose difficulties when presenting with usual clinico-radiologic features and morphology. Pathology textbooks and national/international guidelines generally describe the findings of classic MPM, underlining common clinical presentation, the gold standard of sampling techniques, usual morphologic variants, immunohistochemical results of several positive and negative primary antibodies in the differential diagnosis, and the role of novel molecular markers. Nevertheless, MPM often does not follow the golden rules in routine practice, while the literature generally does not sufficiently emphasize unusual features of its manifestation. This gap may potentially create problems for patients in sustaining a difficult diagnosis of MPM in clinical practice and during legal disputes. Indeed, the guidelines accidentally tend to favor the job of lawyers and pathologists defending asbestos-producing industries against patients suffering from MPM characterized by uncommon features. The current review is aimed at underlining the wide spectrum of clinical and radiological presentation of MPM, the possibility to consistently use cytology for diagnostic intent, the aberrant immunohistochemical expression using so-called specific negative and positive primary antibodies, and finally proposing some alternative and more unbiased approaches to the diagnosis of MPM.
Should Lung-Sparing Surgery Be the Standard Procedure for Malignant Pleural Mesothelioma?. Y. Ichiki, H. Goto, T. Fukuyama, et al. 2020;9(7). Review PubMed · Publisher · Free full text

Abstract

Background: Surgical procedures for malignant pleural mesothelioma (MPM) include extrapleural pneumonectomy (EPP), extended pleurectomy/decortication (P/D) and P/D. EPP has been applied to MPM for a long time, but the postoperative status is extremely poor due to the loss of one whole lung. We compared the mortality, morbidity and median survival time (MST) of lung-sparing surgery (extended P/D or P/D) and lung-sacrificing surgery (EPP) for MPM by performing a systematic review.

Methods: We extracted the number of events and patients from the literature identified in electronic databases. Ultimately, 15 reports were selected, and 2674 MPM patients, including 1434 patients undergoing EPP and 1240 patients undergoing extended P/D or P/D, were analyzed.

Results: Our systematic review showed that lung-sparing surgery was significantly superior to lung-sacrificing surgery in both the surgical-related mortality (extended P/D vs. EPP: 3.19% vs. 7.65%, p < 0.01; P/D vs. EPP: 1.85% vs. 7.34%, p < 0.01) and morbidity (extended P/D vs. EPP: 35.7% vs. 60.0%, p < 0.01; P/D vs. EPP: 9.52% vs. 20.89%, p < 0.01). Lung-sparing surgery was not inferior to EPP in terms of MST.

Conclusion: Although no prospective randomized controlled trial has been conducted, it may be time to change the standard surgical method for MPM from lung-sacrificing surgery to lung-sparing surgery.

2010s

Physician Empathy Interacts with Breaking Bad News in Predicting Lung Cancer and Pleural Mesothelioma Patient Survival: Timing May Be Crucial. S. Lelorain, A. Cortot, V. Christophe, et al. 2018;7(10). PubMed · Publisher · Free full text

Abstract

This study is the first to examine the prognostic role of physician empathy in interaction with the type of consultation (TC) (TC, bad news versus follow-up consultations) in cancer patient survival. Between January 2015 and March 2016, 179 outpatients with thoracic cancer and a Karnofsky performance status ≥60 assessed their oncologist's empathy using the CARE questionnaire, which provides a general score and two sub-dimensions: listening/compassion and active/positive empathy. Survival was recorded until April 2018. Usual medical, social and psychological confounders were included in the Cox regression. The median follow-up time was 3.1 years. There was a statistical interaction between listening/compassion empathy and TC (p = 0.016) such that in bad news consultations, higher listening/compassion predicted a higher risk of death (hazard ratio (HR) = 1.13; 95% confidence interval (CI): 1.03⁻1.23; p = 0.008). In follow-up consultations, listening/compassion did not predict survival (HR = 0.94; 95% CI: 0.85⁻1.05; p = 0.30). The same results were found with the general score of empathy, but not with active/positive empathy. In bad news consultations, high patient-perceived physician compassion could worry patients by conveying the idea that there is no longer any hope, which could hasten death. Further studies are warranted to confirm these results and find out the determinants of patient perception of physician empathy.

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