Journal of Thoracic Disease

About the journal

Publisher: AME Publishing Company
Published: 2009 to the present, China
Language: English
ISSN: 2072-1439 (print), 2077-6624 (electronic)
Its record in the NLM Catalog

2020s

Clinical research advances in thoracic surgery and thoracic oncology in 2025: a panoramic narrative review. Z. Sun, X. Li, Z. Hao, et al. 2026;18(4):424. Review PubMed · Publisher · Free full text

Abstract

Background And Objective: The year 2025 brought important refinements in thoracic surgery and thoracic oncology, particularly in risk-adapted screening, biomarker-guided perioperative therapy, minimally invasive surgery, and perioperative recovery. This narrative review summarizes clinically relevant evidence reported in 2025 and discusses how these updates may influence multidisciplinary practice.

Methods: We conducted a narrative review of literature and conference reports published or presented between January 1 and December 31, 2025. PubMed, Google Scholar, and the official abstract proceedings/websites of the American Society of Clinical Oncology (ASCO), the World Conference on Lung Cancer (WCLC), and the European Society for Medical Oncology (ESMO) were searched using combinations of disease-, treatment-, and surgery-related keywords. Earlier pivotal trials were cited selectively to provide background context where needed.

Key Content And Findings: The National Comprehensive Cancer Network (NCCN) updated lung cancer screening criteria toward broader risk inclusion. In resectable non-small cell lung cancer (NSCLC), 2025 data further refined perioperative strategies for molecularly selected and driver-negative populations, including long-term outcomes from immunotherapy trials and phase III evidence for neoadjuvant targeted therapy. Robot-assisted thoracic surgery (RATS) continued to show advantages in selected complex settings, especially after induction treatment. Progress in mesothelioma, esophageal cancer, perioperative rehabilitation, and digital symptom monitoring also underscored the increasing importance of whole-patient care. However, several emerging tools, including circulating tumor DNA (ctDNA) and artificial intelligence (AI)-assisted models, still require prospective validation, standardization, and broader accessibility before routine implementation.

Conclusions: Recent advances in thoracic oncology increasingly support a more precise, multidisciplinary, and patient-centered model of care. The most meaningful progress in 2025 lay not only in new treatments, but also in better integration of molecular stratification, surgical decision-making, and perioperative management.

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Experience of biological implants in thoracic surgery for soft tissue and chest wall reconstruction in clean and contaminated environments. H. Jesani, V. Surendrakumar, H. Walji, et al. 2026;18(8):931. PubMed · Publisher · Free full text

Abstract

Background: Biological mesh has become an integral tool in surgery for reconstructive procedures. Acellular dermal matrices derived from porcine or bovine collagen scaffolds provide a durable implant material for use in reconstruction of the chest wall, and soft tissues including the pericardium and diaphragm. We aimed to present our experience of biological meshes used for thoracic reconstructive procedures for a wide range of clinical indications by a single surgeon, comparing the effect of contaminated and clean surgical environments and implant materials.

Methods: We retrospectively reviewed all patients who had undergone thoracic surgery reconstructive procedures under a single surgical team with biological mesh material over a 16-year period from March 2009 to April 2025. Data included indication for surgery, operative procedure, surgical site, biological implant material (cross-linked or non-cross-linked), postoperative infection, in-hospital mortality and reoperation rate. We directly compared the results between patients undergoing the procedure in infected/contaminated versus clean cases.

Results: In total 152 consecutive procedures were performed utilising 212 patches. Median age was 65 years (range, 24-84 years) and majority treated were males 104/152 (68%). Indications for surgery included total pleurectomy for mesothelioma (38%), resection of extended thoracic malignancy (33%), surgery for trauma or related complications (19%), and benign conditions including adult congenital abnormalities (10%). Cross-linked biological mesh had a significantly reduced surgical site infection rate compared to non-cross-linked biological mesh (n=6; 7% vs. n=16; 23%, P=0.008). This remained significant following adjustment for key clinical confounding factors [adjusted odds ratio (OR) 0.289, 95% confidence interval (CI): 0.105-0.793, P=0.02]. Direct comparison of contaminated environments versus clean showed surgical site infections postoperatively were not significantly different (24% vs. 12% P=0.09). No biological patch necessitated explantation due to infection. In-hospital mortality and reoperation rates remained low at 4% and 9% respectively.

Conclusions: Our study evaluates and supports the continued use of biological patches for thoracic reconstruction of soft tissues and chest wall. Biological patches have a role in a diverse range of surgical indications including extended resection of malignancy and traumatic injuries and can be feasibly used in high risk contaminated surgical fields.

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Hidden in plain sight: a narrative review on environmental exposures and the fight against mesothelioma. P. Behinaein, J.N. Patel, I. Okereke. 2026;18(2):166. Review PubMed · Publisher · Free full text

Abstract

Background And Objective: Mesothelioma remains lethal, with a growing share linked to non-occupational exposure in community settings. This review synthesizes contemporary epidemiology, mechanisms, exposure sources, diagnosis, treatment and public health strategies.

Methods: This narrative review was conducted to synthesize heterogeneous evidence addressing environmental and para-occupational asbestos exposure and its relationship to malignant mesothelioma. A structured literature search was performed using PubMed/MEDLINE, Embase, and Web of Science databases for articles published through 2025. Terms related exclusively to occupational exposure were deliberately deprioritized. Studies were eligible for inclusion if they met at least one of the following criteria: (I) epidemiological investigations evaluating non-occupational, environmental, or para-occupational asbestos exposure; (II) mechanistic or toxicological studies elucidating fiber pathogenicity relevant to environmental exposure scenarios; (III) investigations of population clusters associated with naturally occurring or construction-related mineral fibers; (IV) studies assessing environmental remediation, surveillance strategies, or public-health interventions; or (V) clinical investigations reporting data stratified by exposure category. Articles focusing exclusively on occupational exposure without environmental relevance were excluded. Case reports without exposure characterization, editorials without primary data, and studies lacking clear methodological description were also excluded.

Key Content And Findings: Environmental risk arises from naturally occurring asbestos (NOA), legacy building materials, industrial residues and para-occupational transfer into homes. Case mix is shifting toward women, younger patients and peritoneal presentations in geologic or industrial hotspots. Fiber biopersistence drives chronic inflammation, oxidative injury and mesothelial transformation. Systemic therapy now centers on dual checkpoint blockade as a first-line standard, with chemo-immunotherapy and platinum-pemetrexed backbones, and selective use of bevacizumab. Surgery is reserved for candidates in expert centers, favoring lung-sparing pleurectomy and decortication when macroscopic clearance is plausible. Prevention requires total prohibition of new asbestos use, disciplined legacy management, robust enforcement, land-use controls in NOA terrains, and household protections.

Conclusions: Environmental drivers will sustain mesothelioma burden unless exposure pathways are eliminated and legacy sources are controlled. Clinical gains come from immunotherapy, selective surgery and coordinated supportive care, but prevention and earlier detection carry the greatest impact. A unified agenda that couples exposure science with equitable public health action is essential to bend incidence and improve outcomes.

© AME Publishing Company.
Hyperthermic intrathoracic chemotherapy after cytoreductive surgery in malignant pleural mesothelioma: a single-center retrospective cohort study suggesting increased morbidity without survival benefit. N. Baldes, F. Doerr, K. Grapatsas, et al. 2026;18(8):831. PubMed · Publisher · Free full text

Abstract

Background: In the multimodal treatment of pleural mesothelioma (PM), hyperthermic intrathoracic chemotherapy (HITOC) has been investigated as an adjunct to cytoreductive surgery (CRS) to potentially improve local tumor control. The study aimed to evaluate the clinical impact of HITOC as an adjunct to CRS, specifically regarding overall survival (OS), postoperative morbidity and mortality, and operative duration.

Methods: This retrospective study compared patients who underwent CRS with HITOC to those without HITOC at our institution between 2010 and 2022. Primary endpoints included OS, operative time, and perioperative morbidity and mortality. Categorical variables were compared using the Fisher's exact test. Survival analyses were performed using the Kaplan-Meier method and compared via the log-rank test.

Results: A total of 114 patients underwent CRS for PM, including 14 with HITOC and 100 without. The mean age was 66 years, and 12 patients were female. The mean operative time was longer in the HITOC group (488 vs. 258 minutes). Postoperative morbidity (Clavien-Dindo Grade ≥ III) was significantly higher with HITOC [43 % vs. 10 %, odds ratio (OR) 6.07, 95 % confidence interval (CI): 1.77-20.76, P=0.007], while in-hospital mortality occurred in two patients (1.8 %), one in each group. Median OS was 13 months in the HITOC group vs. 27 months in the non-HITOC group (P=0.03).

Conclusions: In this retrospective single-center cohort, adjunctive HITOC was associated with significantly longer operative time, higher postoperative morbidity, and inferior OS compared with cytoreduction alone. Given the small HITOC sample size and potential residual confounding, these findings should be interpreted cautiously but raise concerns regarding the routine use of HITOC outside clinical trials and highlight the need for prospective comparative evaluation.

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Impact of intercostal nerve cryoablation on opioid use in pleural mesothelioma surgery: results from a high-volume integrated regional center. A.S. Baskin, S. Elmankabadi, V. Zhang, et al. 2026;18(4):309. PubMed · Publisher · Free full text

Abstract

Background: Pleural mesothelioma is a rare and aggressive malignancy treated with a multimodal approach that includes surgery. Unfortunately, pleurectomy and decortication surgery is highly morbid and is associated with significant postoperative pain. To reduce harmful side effects associated with opioid use, intercostal nerve cryoablation has emerged as a potential adjunct for thoracic pain control. However, its role among patients with pleural mesothelioma has not been established. We aimed to evaluate whether intercostal nerve cryoablation reduces inpatient opioid use among patients undergoing pleurectomy and decortication for pleural mesothelioma.

Methods: In 2024, our regionalized surgical practice began using cryoablation as an adjunct to standard-of-care analgesia following pleurectomy and decortication. The cryoSPHERE ablation probe (AtriCure) was uniformly applied to the 4th-8th intercostal spaces under direct visualization and was cooled to -60 ℃, and was held at each intercostal space for 2 minutes. We retrospectively compared patients with pleural mesothelioma who underwent pleurectomy and decortication and received cryoablation (surgery in 2024) to those who did not receive cryoablation (surgery between 2015 and 2023). The primary outcome was inpatient opioid consumption [morphine milligram equivalents (MME)]. We also evaluated the proportion of patients requiring no inpatient opioids, neuropathic symptoms, pain scores, epidural duration, hospital length of stay (LOS), and 30-day postoperative complications.

Results: Among 64 patients, 22 (34%) received cryoablation and 42 (66%) did not. Those with cryoablation had lower median opioid use [145 MME; interquartile range (IQR), 22-464 MME] than those who did not (254 MME; IQR, 87-503 MME), although this difference was not statistically significant (P=0.46). Five (23%) patients with cryoablation required no inpatient opioids compared to 5 (12%) patients without cryoablation (P=0.29). There were no neuropathic symptoms observed with cryoablation. Additionally, there were no differences in pain scores, epidural duration, LOS, and 30-day complications between cohorts.

Conclusions: In this real-world cohort of patients with pleural mesothelioma treated at a large integrated healthcare system, cryoablation was associated with a trend toward reduced postoperative opioid use without compromising pain control compared to standard-of-care analgesia. Cryoablation was not associated with neuropathic symptoms or increased 30-day postoperative complications. Although not statistically significant, the absolute reduction of 109 MME suggests a potential clinical benefit from adjunctive cryoablation during pleurectomy and decortication, especially given its favorable safety profile. Further studies are warranted to clarify cryoablation's role and identify the patients most likely to benefit.

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Occupational asbestos exposure and lung cancer: contemporary research trends, exploratory genetic evidence, and global burden from 1990 to 2021. Y. Chen, C. Gao, X. Lou, et al. 2026;18(9):1034. PubMed · Publisher · Free full text

Abstract

Background: Asbestos exposure is a confirmed risk factor for lung cancer, but its causal relationship with different subtypes and its global disease burden remain poorly characterized. This study aims to comprehensively evaluate the association between occupational asbestos exposure and lung cancer through multidimensional analysis, integrating bibliometric analysis, mendelian randomization, and Global Burden of Disease data to identify research trends, explore potential subtype-specific associations, and characterize global disease burden patterns.

Methods: This study included a bibliometric analysis of publications from the Web of Science Core Collection on asbestos-related lung cancer. Mendelian randomization was performed using OpenGWAS data to investigate whether asbestos exposure is differentially associated with specific lung cancer subtypes. Global Burden of Disease 2021 data were analyzed to estimate the asbestos-related lung cancer burden by age and sex. Future burden was projected using the Bayesian age-period-cohort model.

Results: Bibliometrics revealed fluctuating publication trends, with a thematic shift toward molecular mechanisms. Mendelian randomization analysis identified a suggestive causal relationship between asbestos exposure and lung adenocarcinoma [odds ratio (OR) =4.901, 95% confidence interval (CI): 1.150-20.881, P=0.03], but no significant causal links were observed with overall lung cancer or other subtypes. None of the instrumental variables demonstrated horizontal pleiotropy or heterogeneity. Global Burden of Disease analysis showed a higher asbestos-related lung cancer burden in males and older populations, with the greatest attributable burden in high socio-demographic index regions. Projections indicate a continued decline in global burden by 2036.

Conclusions: The mendelian randomization results offer genetic evidence supporting a specific causal role of asbestos in lung adenocarcinoma development. Despite a decline in burden due to control policies, ongoing exposure in developing countries and legacy asbestos in buildings remain serious challenges. Future research should focus on larger genetic studies and analysis tailored to subtypes, while global efforts need to prioritize a comprehensive asbestos ban, improved screening for high-risk groups, and enhanced international cooperation to eliminate asbestos-related diseases.

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Predictors of pleurodesis success after combined outpatient thoracoscopic talc poudrage and tunneled indwelling pleural catheter placement. M. Bani Salem, O. Al Zoubi, T. Maser, et al. 2026;18(9):1011. PubMed · Publisher · Free full text

Abstract

Background: Combined ambulatory thoracoscopic talc poudrage and tunneled indwelling pleural catheter (TIPC) placement may facilitate early pleurodesis while preserving outpatient management for malignant pleural effusion (MPE). Predictors of pleurodesis success after this combined approach remain incompletely defined. In this study, we aimed to identify the predictors of successful pleurodesis after this combined approach among patients with expandable and non-expandable lung subgroups.

Methods: We performed a retrospective cohort study of 100 patients who underwent outpatient thoracoscopic talc poudrage with TIPC placement for MPE. Pleurodesis success was assessed at 3 and 6 months. Multivariable logistic regression was used to identify predictors of success among 97 evaluable patients. Additional analyses were performed in the non-expandable lung subgroup.

Results: Among 97 patients, 77 (79.4%) had expandable lungs. In multivariable analysis, lung expandability was independently associated with pleurodesis success at 3 months [odds ratio (OR), 15.2; 95% confidence interval (CI): 4.22-71.0; P<0.001] and 6 months (OR, 7.97; 95% CI: 2.07-33.9; P=0.003). Cancer group was associated with 3-month success in adjusted analysis (global P=0.046): compared with the lung/mesothelioma group, the other-malignancy group had lower odds of success (OR, 0.19; 95% CI: 0.04-0.73), whereas breast cancer did not differ significantly. No group difference persisted at 6 months (global P=0.46). Lung/mesothelioma-associated MPE had higher early pleurodesis success than other malignancy groups, but not at 6 months. In the non-expandable lung subgroup, complete visceral restriction, airway obstruction and adhesions were associated with lower 6-month pleurodesis success on univariate analysis.

Conclusions: Lung expandability was the strongest independent predictor of pleurodesis success after combined outpatient thoracoscopic talc poudrage and TIPC placement. Selected patients with non-expandable lung may still achieve successful pleurodesis.

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Pressurized intrathoracic aerosol chemotherapy (PITAC) for malignant pleural mesothelioma-ex vivo evaluation of optimal treatment conditions and comparison with hyperthermic intrathoracic chemotherapy (HITOC). K. Flöthmann, N. Zinne, P. Braubach, et al. 2026;18(5):516. PubMed · Publisher · Free full text

Abstract

Background: Malignant pleural mesothelioma (MPM) is a rare but aggressive disease with poor prognosis and limited treatment options. Pressurized intrathoracic aerosol chemotherapy (PITAC) has emerged as a novel approach for intrathoracic drug delivery. The aim of this study was to investigate cisplatin penetration characteristics and to evaluate procedural parameters influencing drug penetration, including temperature, drug concentration and pleural barrier function, in an ex vivo model. In addition, PITAC was compared with hyperthermic intrathoracic chemotherapy (HITOC), a treatment modality applied in selected specialized centers as part of multimodal treatment concepts for MPM.

Methods: We investigated the penetration depth and intensity of aerosolized cisplatin generated using a high-pressure nebulizer in an ex vivo setting. Potential influencing factors, including temperature, cisplatin concentration and barrier function of the pleura, were gradually modified, as we sought to evaluate optimal procedural conditions. Finally, PITAC was compared with a previously standardized HITOC approach.

Results: A temperature of 42 ℃, a cisplatin concentration of 1 mg/mL, and prior removal of the pleura, improved the penetration depth and intensity of the chemotherapeutic agent. Under clinically relevant experimental conditions, aerosolized cisplatin application demonstrated greater tissue penetration compared to HITOC.

Conclusions: Our preclinical data suggest that PITAC may be a viable alternative to HITOC and warrants further clinical investigation.

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Retrospective cohort study on prognostic factors of malignant pleural effusion secondary to pleural mesothelioma. X. Qiao, J.J. Zhang, B. Liu, et al. 2026;18(7):731. PubMed · Publisher · Free full text

Abstract

Background: Malignant pleural effusion (MPE) frequently complicates pleural mesothelioma; however, prognostic determinants for this condition, particularly pleural fluid biomarkers, have yet to be comprehensively characterized. This study sought to assess the prognostic utility of clinical profiles and laboratory findings, with a specific focus on pleural fluid parameters, in patients with mesothelioma-associated MPE.

Methods: This retrospective cohort study included patients diagnosed with MPE secondary to pleural mesothelioma at Tianjin Chest Hospital from January 2015 to May 2025. Inclusion criteria: age ≥18 years, confirmed diagnosis. Exclusion criteria: active infection, incomplete baseline clinical/laboratory data, or prior anti-tumor therapy. Follow-up was conducted via telephone at monthly intervals for 6 months then every 3 months. The primary outcome was overall survival (OS), defined as time from diagnosis to death or last follow-up. Univariable and multivariable Cox regression analyses were performed to identify independent prognostic factors.

Results: Seventy‑one eligible patients were analyzed. Median OS was 30 months (range, 16-44 months). Four factors were independently associated with OS in multivariable analysis: pleural fluid lactate dehydrogenase (LDH) ≥361 U/L [hazard ratio (HR) 4.373, 95% confidence interval (CI): 1.903-10.049, P=0.001], fibrinogen (FIB) ≥3.82 g/L (HR 3.592, 95% CI: 1.683-7.666, P=0.001), mean platelet volume (MPV) ≥12.50 fL (HR 2.507, 95% CI: 1.125-5.586, P=0.03), and absolute lymphocyte count ≥1.48×109/L (HR 0.423, 95% CI: 0.204-0.877, P=0.02).

Conclusions: These four routinely available baseline parameters-pleural fluid LDH, FIB, MPV, and absolute lymphocyte count-may serve as potential prognostic indicators in patients with MPE secondary to pleural mesothelioma. Prospective, multicenter studies with external validation are required to confirm these findings.

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A bibliometric analysis of malignant pleural mesothelioma from 2010 to 2023. S. Chen, C. Zhao, R. Liu, et al. 2025;17(4):2014-2027. PubMed · Publisher · Free full text

Abstract

Background: Malignant pleural mesothelioma (MPM) is an aggressive tumor originating from the mesothelial lining of the pleural cavity. It is characterized by extensive nodular pleural thickening and has a propensity to invade the pleural adipose tissue and adjacent chest structures. The prognosis is poor, with a median survival time rarely exceeding 12 months following diagnosis.

Methods: This bibliometric analysis systematically assessed global trends in MPM research from 2010 to 2023 using 6,487 publications indexed in PubMed. Quantitative evaluations of publication metrics, international collaboration, and keyword co-occurrence networks were conducted using R software with the bibliometrix package. Network construction and thematic mapping were employed to analyze the temporal evolution of research topics.

Results: The United States and Europe have played pivotal roles in this research, while contributions from China and Japan have been steadily increasing. Traditional treatment approaches and etiological studies are relatively well-established. Meanwhile, immunotherapy has emerged as a prominent focus of recent research.

Conclusions: Future global collaboration in this field should be enhanced, as precision medicine related to immunology and genetics has the potential to transform the treatment landscape of MPM.

Copyright © 2025 AME Publishing Company. All rights reserved.
CD276 as a critical independent biomarker and immune checkpoint inhibitor target in epithelioid mesothelioma-TCGA study. Y. Aoki, K. Arimura, K. Hiroshima, et al. 2025;17(1):109-120. PubMed · Publisher · Free full text

Abstract

Background: CD276 is an immune checkpoint, and immune checkpoint inhibitors (ICIs) targeting CD276 have been tested against various cancers. However, the precise role of CD276 in mesothelioma subtypes is unknown. This study aimed to reveal the prognostic significance of CD276 in various cancers and explore CD276 as a target for ICIs in different mesothelioma subtypes.

Methods: We evaluated data from The Cancer Genome Atlas (TCGA) database retrospectively. The Wilcoxon rank-sum test was used to assess CD276 mRNA expression between cancer tissues and the adjacent normal tissues in the context of various cancers. The study involved 86 patients with mesothelioma. The mean number of patients was set as the cutoff value for comparing CD276 mRNA expression. The overall survival (OS) of patients with each mesothelioma subtype was estimated using the Kaplan-Meier method with CD276 mRNA expression. The factors affecting the correlation between OS and high/low CD276 expression in combination with/without a current existing molecular targets of programmed cell death 1 (PD-1), cytotoxic T-lymphocyte-associated protein 4 (CTLA4), and vascular endothelial growth factor A (VEGFA) were assessed using a multivariate Cox proportional hazards model. The correlation between the mRNA expression of CD276 and expression of gene markers of tumor-infiltrating immune cells and those of different pathways was evaluated using Spearman's correlation. The factors affecting correlations of CD276 mRNA expression were confirmed using a multivariate linear regression model.

Results: Upregulated CD276 mRNA expression was associated with a poor prognosis in various cancers, including epithelioid mesothelioma. The multivariate Cox proportional hazards model demonstrated that upregulated CD276 mRNA expression indicated the worst prognosis, including the combination of CD276 and PD-1, CTLA4, and VEGFA. In addition, using a multivariate linear regression model, CD276 mRNA expression was found to correlate with multiple glycolytic pathway mRNAs in epithelioid mesothelioma, especially PKM2.

Conclusions: CD276 is an independent prognostic biomarker in patients with epithelioid mesothelioma. It is associated with the glycolytic pathway and may contribute to ATP generation in epithelioid mesothelioma. CD276 inhibitors might contribute to better prognosis in patients with epithelioid mesothelioma.

Copyright © 2025 AME Publishing Company. All rights reserved.
Global bibliometric analysis of pleural mesothelioma biomarkers (2002-2024): trends and emerging frontiers. S. Huang, Q. Duan, D. Gu, et al. 2025;17(12):10771-10790. PubMed · Publisher · Free full text

Abstract

Background: Pleural mesothelioma (PM) is an aggressive malignancy that originates on the mesothelial surface of the pleura, peritoneum, pericardium, and tunica vaginalis. Due to the absence of specific clinical symptoms, early-stage diagnosis occurs in fewer than 5% of cases. Comprehensive assessments of the research landscape on PM biomarkers remain scarce. Therefore, this study employs bibliometric methods to systematically analyze research trends and developments in PM biomarkers, delineate the historical and current research landscape, and identify emerging research frontiers.

Methods: We conducted a literature search for studies on PM biomarkers published between January 1, 2002, and December 31, 2024. Bibliometric analysis and data visualization were performed using VOSviewer and CiteSpace based on literature retrieved from the Web of Science Core Collection (WoSCC).

Results: A total of 662 publications on PM biomarkers, spanning from 2002 to 2024, were included in this study. Our findings reveal a substantial increase in global research on PM biomarkers over the past two decades, with annual publications peaking in 2021. The United States leads in publication volume, while the University of Western Australia ranks as the most prolific institution in this domain. Jenette Creaney, Glen Reid, and Harvey I. Pass are among the most influential authors in this field, while Journal of Thoracic Oncology, PLoS One, and Lung Cancer are the leading journals publishing research on this topic. Biomarkers associated with the diagnosis, treatment, and prognosis of PM remain central research foci in the field.

Conclusions: This study represents the first bibliometric visualization of the research landscape on PM biomarkers, delineating key trends and research boundaries while serving as a valuable reference for scholars.

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Inclusion of anti-vascular therapy as a promising option for later-line treatment of malignant pleural mesothelioma: a retrospective study. K. Shao, D. Wu, Q. Wang, et al. 2025;17(8):5687-5697. PubMed · Publisher · Free full text

Abstract

Background: Malignant pleural mesothelioma (MPM) is a highly aggressive malignancy with a poor prognosis. While pemetrexed-based chemotherapy and dual immunotherapy are established first-line treatments, optimal second- and later-line therapies remain underexplored. This study aims to evaluate later-line treatment options for MPM.

Methods: We retrospectively evaluated the outcomes of 85 patients with MPM who had failed in the first-line treatment between 2006 and 2023 in six hospitals. Survival outcomes were analyzed using Kaplan-Meier methodology, with between-group comparisons performed via log-rank testing. The Cox proportional hazards model was employed for both univariate and multivariate analyses to identify prognostic factors. Treatment response was assessed using standard efficacy endpoints: objective response rate (ORR) and disease control rate (DCR).

Results: This retrospective analysis evaluated 85 patients with advanced MPM. The cohort demonstrated a median progression-free survival (PFS) of 3.73 months and a median overall survival (OS) of 12.4 months. In the later-line, combining chemotherapy with anti-vascular therapy showed significant efficacy in median PFS than the chemotherapy scheme (4.57 vs. 3.00 months, P=0.004), as well as differences in median OS (13.00 vs. 10.03 months, P=0.04).

Conclusions: For patients with MPM requiring later-line treatment, the combination of chemotherapy and anti-vascular therapy may represent a viable therapeutic alternative, demonstrating an acceptable safety profile.

Copyright © 2025 AME Publishing Company. All rights reserved.
The transparency and public availability of asbestos exposure levels. M. Shepard, L. Binelli, I.C. Okereke. 2025;17(12):11465-11477. Review PubMed · Publisher · Free full text

Abstract

Asbestos exposure continues to be a critical public health concern due to its established link with serious respiratory diseases and malignancies. Despite the attention that asbestos-related disease has received and the litigation that has existed, asbestos-related deaths have increased over time. Public reporting of asbestos levels is essential to inform at-risk populations and facilitate regulatory compliance. Laws and practices regarding measuring of asbestos levels and reporting of these levels vary widely. Each different country has different standards that are applied to reporting. In many countries, legislation that has been passed by governing bodies has affected the amount of asbestos use and the reporting standards. Other countries have depended on community organizations to spread awareness and public pressure regarding standards of reporting. This review summarizes current practices in asbestos monitoring and public reporting, examines the strengths and limitations of existing frameworks, and explores technological and policy innovations aimed at improving transparency and public awareness. Enhancing data accessibility and public engagement remains vital to reducing asbestos-related health risks worldwide. Creating a uniform policy as widely as possible regarding asbestos reporting will empower the public and aid in reducing harm from asbestos-related disease. Future efforts should focus on creating comprehensive reporting policies and facilitating the ease at which the public can access this data.

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Incidence, mortality and survival of pleural mesothelioma in Zurich between 1981 and 2019, Switzerland. L. Vinci, M. Wanner, N. Karavasiloglou, et al. 2024;16(12):8240-8249. PubMed · Publisher · Free full text

Abstract

Background: Pleural mesothelioma is mainly caused by (occupational) asbestos exposure. Since 1990, the import and use of asbestos is prohibited in Switzerland. However, due to the long latency time between exposure and the development of disease, incidence in Switzerland was expected to further increase for years after the ban. The aim of the present study was to analyse incidence, mortality, and survival of patients diagnosed with malignant pleural mesothelioma in the canton of Zurich in Switzerland.

Methods: Population-based cancer registry data and cause of death statistics of the canton of Zurich from 1981 to 2019 were used to calculate age-standardized incidence and mortality rates. Time trends were investigated with joinpoint regression and net survival was computed using the Pohar-Perme method.

Results: In men, the incidence rate increased from 1981 to 2002 {annual percentage change (APC) 4.7 [95% confidence interval (CI): 2.6 to 6.8]} and then decreased until 2019 [APC: -2.3 (95% CI: -4.2 to -0.3)], while in women it increased over the whole period [APC 6.2 (95% CI: -1.3 to 14.4)]. Mortality rates were stable in men and women. Three-year net survival was 9.7% (95% CI: 7.8% to 12.2%) for men and 22.1% (95% CI: 15.3% to 32.1%) for women. Men with stage I or II pleural mesothelioma had a net survival of 25.4% (95% CI: 17.2% to 37.5%) after three years whereas men with stage III or IV experienced a net survival of 7.4% (95% CI: 3.9% to 13.8%) after three years.

Conclusions: Malignant pleural mesothelioma incidence seems to have reached the peak in the canton of Zurich in men, but not yet in women. Mortality rates were stable in men and women, and net survival was poor for both sexes, particularly in men.

2024 AME Publishing Company. All rights reserved.
Malignant pleural mesothelioma treated with cytoreductive video-assisted thoracic surgery plus hyperthermic intrathoracic chemotherapy: a case report. D. Li, Y. Cao, F. Petrella, et al. 2024;16(11):8133-8141. Case report PubMed · Publisher · Free full text

Abstract

Background: Malignant pleural mesothelioma (MPM) is primarily treated with a combination therapy based on lung pleurectomy in the early stage or pemetrexed combined with platinum-based chemotherapy in the late stage. However, these standard therapies do not significantly improve survival and are associated with significant adverse reactions.

Case Description: In February 2017, a 63-year-old male patient was admitted to Department of Thoracic Surgery, The Third Affiliated Hospital of Chongqing Medical University coughing for 1 month and experienced chest tightness and chest pain for 2 days. After admission, the patient underwent thoracic puncture drainage and was diagnosed with stage IIIb (c-T4NxM0) MPM. The patient subsequently underwent left pleural biopsy under single-port thoracoscopy, followed by cytoreductive surgery plus hyperthermic intrathoracic chemotherapy as a local treatment for controlling pleural effusion. At a postoperative follow-up in October 2017, we found that he had recurrent MPM with multiple nodules on the left pleura. Despite this, the patient declined further antitumor treatment. In April 2020, the patient was readmitted to The Third Affiliated Hospital of Chongqing Medical University for left-sided chest pain and was observed to have an enlarged tumor in the left pleural according to further imaging examination. Fortunately, no further pleural effusion has been observed since then. Subsequently, the patient was administered a combination of immunotherapy and cisplatin-pemetrexed chemotherapy as systemic therapy for six cycles, along with subsequent mono immunotherapy as maintenance therapy for three additional cycles. Following this, the left pleural tumor shrank significantly, and the patient achieved partial remission. However, due to the patient's irregular treatment adherence, the patient returned for systemic immunotherapy therapy for four cycles in November 2021, and a slight reduction of the pleural tumor was achieved. Once again, the patient discontinued treatment until he experienced left-sided chest pain and partial tumor enlargement in February 2023. Another three cycles of immunotherapy were administered, but the pleural tumor continued to grow. In June 2023, the patient succumbed to respiratory failure caused by a pulmonary infection. Overall, the patient's survival time was 76 months.

Conclusions: Cytoreductive video-assisted thoracic surgery plus hyperthermic intrathoracic chemotherapy followed by systemic chemo-immunotherapy can effectively control pleural effusion, prolong patient survival, and improve the quality of life in patients with MPM.

2024 AME Publishing Company. All rights reserved.
Pleural fluid biomarkers: a narrative review. C. Chan, K.K.P. Chan. 2024;16(7):4764-4771. Review PubMed · Publisher · Free full text

Abstract

Background And Objective: Pleural fluid is a source from which various biomarkers can be obtained and measured to facilitate the management and prognostication of various conditions. This narrative review aims to summarise a few selected applications of pleural fluid biomarker analysis based on the latest literature.

Methods: A literature search for articles published in English regarding human subjects from the period January 2000 to December 2023 was performed through PubMed. Publications considered by the authors to be relevant were included in this review, with additional references added based on the authors' judgement. This review considered both prospective and retrospective cohort studies analysing the clinical value of a range of pleural fluid biomarkers.

Key Content And Findings: The biomarkers selected in this narrative review have either established clinical applicability or promising initial results which require further research. Pleural fluid adenosine deaminase, mesothelin and N-terminal pro-B-type natriuretic peptide can optimize the diagnosis of tuberculous pleuritis, malignant mesothelioma and heart failure-related pleural effusion respectively. The detection rate for epidermal growth factor receptor mutations for lung cancer is higher in the pleural fluid than in the pleural tissue or plasma. Suitable targeted therapy in patients with detectable mutations can offer survival benefits. The pleural fluid neutrophil-lymphocyte ratio, soluble urokinase plasminogen activator receptor and plasminogen activator inhibitor 1 carry prognostic implications and can potentially guide subsequent treatment decisions. These biomarkers used individually, or in conjunction with other clinical parameters, should only be utilised in pre-defined, appropriate clinical conditions to maximize their clinical value.

Conclusions: A great variety of different biomarkers are available for analysis in pleural fluid. Further research and development are necessary to widen the spectrum and enhance the clinical utility of pleural fluid biomarkers. Comparison with the diagnostic utilities of serum biomarkers and other investigation parameters, such as radiological findings, could be considered when evaluating the performance of pleural fluid biomarkers.

2024 Journal of Thoracic Disease. All rights reserved.
The genetic susceptibility in the development of malignant pleural mesothelioma: somatic and germline variants, clinicopathological features and implication in practical medical/surgical care: a narrative review. M.T. Congedo, E.C. West, J. Evangelista, et al. 2024;16(1):671-687. Review PubMed · Publisher · Free full text

Abstract

Background And Objective: Malignant pleural mesothelioma (MPM) is a very aggressive primary tumor of the pleura whose main risk factor is exposure to asbestos. However, only a minority of exposed people develops MPM and the incidence of MPM cases without an apparent association with asbestos exposure has been increasing in recent years, suggesting that genetic predisposing factors may play a crucial role. In addition, several studies reported familial cases of MPM, suggesting that heredity may be an important and underestimated feature in MPM development. Several candidate genes have been associated with a predisposition to MPM and most of them play a role in DNA repair mechanisms: overall, approximately 20% of MPM cases may be related to genetic predisposition. A particular category of patients with high susceptibility to MPM is represented by carriers of pathogenic variants in the BAP1 gene. Germline variants in BAP1 predispose to the development of MPM following an autosomal dominant pattern of inheritance in the familial cases. MPMs in these patients are significantly less aggressive, and patients require a multidisciplinary approach that involves genetic counseling, medical genetics, pathology, surgical, medical, and radiation oncology expertise. In the present narrative review, we presented a comprehensive overview of genetic susceptibility in the development of MPM.

Methods: The narrative review is based on a selective literature carried out in PubMed in 2023. Inclusion criteria were original articles in English language, and clinical trials (randomized, prospective, or retrospective).

Key Content And Findings: We summarized the somatic and germline variants and the differences in terms of clinicopathological features and prognosis between gene-related MPM (GR-MPM) and asbestos-related MPM (AR-MPM). We also discussed the indications for screening, genetic testing, and surveillance of patients with BAP1 germline variants.

Conclusions: In this narrative review, we have emphasized that the BAP1 gene's harmful germline variations are inherited in an autosomal dominant manner in familial cases. MPMs in individuals with these variations are less severe, and their medical care necessitates a collaborative effort. Additionally, we have outlined the current therapeutic prospects for MPM, including the possibility of gene-specific therapy, which is currently promising but still requires clinical validation.

2024 Journal of Thoracic Disease. All rights reserved.
The impact of age on the efficacy of radiotherapy in pleural mesothelioma patients receiving trimodality therapy: a population-based study of the SEER database. J. Yang, L. Xia, H. Jie, et al. 2024;16(10):6462-6474. PubMed · Publisher · Free full text

Abstract

Background: Pleural mesothelioma (PM) is a highly aggressive tumor with poor survival outcomes. The role of additional radiotherapy for PM patients who have received surgery and chemotherapy remains controversial. In this study, we aim to evaluate the impact of age on the effectiveness of additional radiotherapy in order to identify the populations that may benefit from the trimodality therapy.

Methods: We designed a case-control study and retrospectively selected PM patients who underwent surgery and chemotherapy, with or without radiotherapy, from the Surveillance, Epidemiology, and End Results (SEER) database (2000-2019). Kaplan-Meier curves were performed to compare the overall survival (OS) and cancer-specific survival (CSS) between the surgery + chemotherapy group and the trimodality therapy group. Propensity score matching (PSM) was used to balance the clinical characteristics and reduce potential confounding effects.

Results: A total of 745 patients were selected, of which 515 received surgery + chemotherapy and 230 received trimodality therapy. For patients aged 50 to <65 years, additional radiotherapy showed better OS (3-year: 34.78% vs. 23.92%, P=0.02) and CSS (3-year: 36.15% vs. 25.46%, P=0.04) compared to surgery + chemotherapy. Similar results were observed after PSM (3-year OS: 38.76% vs. 26.53%, P=0.02; 3-year CSS: 40.49% vs. 26.92%, P=0.02). No significant benefit of radiotherapy was seen for patients aged <50 and ≥65 years, both before and after PSM.

Conclusions: Our findings reveal that trimodality therapy is associated with better OS and CSS compared to surgery + chemotherapy for patients aged 50 to <65 years. These patients might obtain a benefit from additional radiotherapy.

2024 AME Publishing Company. All rights reserved.
Age and treatment disparities in survival of primary malignant cardiac tumors: an analysis of over 40 years and 500 patients. W. Wang, L. Kang, J. Zhang, et al. 2023;15(8):4434-4444. PubMed · Publisher · Free full text

Abstract

Background: Primary malignant cardiac tumors (PMCTs) are rare and tend to have a poor prognosis, due to their aggressive biological behavior and the inadequate expertise with the disease. This article compares the survival of patients with PMCT subtypes in the United States across age and treatment groups.

Methods: Data of 529 patients diagnosed with PMCTs were analyzed. Chi-squared test was used to assess signiﬁcance of the differences between proportions in demographic and tumor characteristics by age and treatment. Cox regression analysis was used to estimate survival from the Surveillance, Epidemiology, and End Results (SEER) follow-up data.

Results: Survival rates for PMCTs differed significantly between age groups, with patients younger than 20 years surviving significantly longer than those older than 80 years. The median survival times of all patients with PMCTs were 22.5, 11, 5, and 1 month for ages less than 20, 20-50, 51-80, and greater than 80 years, respectively (global log-rank P=0.0026). In the treatment cohort, for all tumors [hazard ratio (HR) 1.52, P<0.001], sarcomas (HR 1.83, P=0.002), and other tumors (HR 2.24, P=0.017), survival was lower in patients who did not receive treatment than in those who received only surgery. Survival after diagnosis of sarcoma was lower in patients who received radiotherapy only than in those who received surgery only (HR 1.49, P=0.046). However, there was no significant association between treatment and survival for lymphoma and mesothelioma.

Conclusions: This study confirms that PMCTs have limited treatment options and poor patient survival, especially for elderly patients and patients who receive no treatment. And patients with PMCTs of any age, whether treated or not, have poor survival rates. Techniques for early diagnosis and treatment may be necessary. Surgical treatment should have a higher priority for future treatment of patients with sarcomas.

2023 Journal of Thoracic Disease. All rights reserved.
Asbestos burden in lungs of non-occupationally exposed women from Broni (Pavia, Italy): a postmortem SEM-EDS study. S.D. Visonà, S. Capella, P. Borrelli, et al. 2023;15(12):6555-6569. PubMed · Publisher · Free full text

Abstract

Background: In Italy the incidence of malignant mesothelioma (MM) among women is remarkably high, due to the several contexts in which women had been exposed to asbestos. However, very few studies in literature focus on the inorganic lung content in women. The aim of this retrospective, observational study is to investigate the asbestos lung burden, in terms of concentration, dimensions and type of asbestos, in 42 women who died from MM and had been non-occupationally exposed to asbestos during the activity of the asbestos-cement plant located in Broni (Pavia, Northern Italy) where mainly chrysotile, crocidolite and amosite were used.

Methods: Lung samples taken during forensic autopsies have been digested using sodium hypochlorite and filtered through a cellulose-ester membrane. The filter was examined using a scanning electron microscope and the chemical composition of the fibers was analyzed using an electron dispersive spectroscopy. The number of detected inorganic fibers, asbestos fibers and asbestos bodies (ABs) were normalized to 1 gram of dry tissue.

Results: In six samples no asbestos has been detected. Overall, the most represented kind of asbestos was amosite, followed by crocidolite, tremolite/actinolite asbestos and chrysotile. The concentration of all inorganic fibers was significantly higher in women with environmental and household exposures compared with those with only environmental exposure (P=0.025), as well as the concentration of asbestos fibers (P=0.019) and ABs (P=0.049). We found a significant correlation between the concentration of asbestos fibers and the duration of exposure (rho =0.413, P=0.008), as well as with the latency of MM (rho =0.427, P=0.005). The distance of the residential address from the factory and the time spent daily in contact with asbestos did not influence the lung asbestos burden.

Conclusions: These results suggest the relevance of the lung clearance of asbestos, regarding mainly chrysotile. As a consequence, although scanning electron microscopy -energy dispersive X-ray spectroscopy (SEM-EDS) is considered the most reliable tool for assessing previous exposure to asbestos, its results should be interpreted with caution, especially in a legal context. In addition, our data confirm the relevance of environmental and household exposure in determining asbestos concentration in lungs and highlight the importance of household exposure.

2023 Journal of Thoracic Disease. All rights reserved.
Hyperthermic intrapleural chemotherapy: an update. M.E. Campany, P.A. Reck Dos Santos, B.B. Donato, et al. 2023;15(9):5064-5073. Review PubMed · Publisher · Free full text

Abstract

The safety and efficacy of hyperthermic intrathoracic chemotherapy (HITHOC) as an adjunct to cytoreductive surgery (CRS) in pleural malignancies has been well demonstrated. This is most often described in cases of mesothelioma, thymoma, or other secondary pleural metastases. The utilization of a direct cytotoxic agent with increased penetration secondary to a hyperthermic environment is especially beneficial in pleural malignancy as a microscopic resection remains immensely challenging. Despite favorable outcomes with a limited associated risk profile, there persists a variety in utilization and technique of HITHOC described in current literature. National Comprehensive Cancer Network (NCCN) guidelines state that though intraoperative adjuvant therapies such as HITHOC have been studied, they remain of unclear benefit and definitive recommendations do not currently exist. This ambiguity limits the standardization of HITHOC, thus hindering its further application in a patient population with exceedingly poor outcomes within current guideline-based therapy. As the prevalence of pleural malignancies necessitating CRS with adjuvant HITHOC remains quite low, we believe a task force initiative to further investigate the role of HITHOC in surgical management of pleural malignancies would enable wider utility of this promising technique. Additionally, we propose that the creation of a pleural cancer index could aid in standardization of HITHOC in those with pleural malignancy.

2023 Journal of Thoracic Disease. All rights reserved.
Impact of guideline therapy on survival of patients with stage I-III epithelioid mesothelioma. D.Z. Liou, Y. Wang, P. Bhandari, et al. 2023;15(12):6661-6673. PubMed · Publisher · Free full text

Abstract

Background: Modern treatment guidelines recommend multimodal therapy with at least chemotherapy and surgery for patients with potentially resectable epithelioid mesothelioma. This study evaluated guideline compliance for patients with stage I-III epithelioid mesothelioma and tested the hypothesis that guideline-concordant therapy improved survival.

Methods: The National Cancer Database was queried for patients with stage I-III epithelioid malignant pleural mesothelioma between 2004 and 2016. The impact of therapy was evaluated using logistic regression, Kaplan-Meier analysis, Cox-proportional hazards analysis, and propensity-scoring methods.

Results: During the study period, guideline-concordant therapy was used in 677 patients (19.1%), and 2,857 patients (80.8%) did not have guideline-concordant therapy. Younger age, being insured, living in a census tract with a higher income, clinical stage, and being treated at an academic or research program were all predictors of receiving guideline-concordant therapy in multivariable analysis. Guideline-concordant therapy yielded improved median survival [24.7 (22.4-26.1) vs. 13.7 (13.2-14.4) months] and 5-year survival [17.7% (14.7-21.3%) vs. 8.0% (7.0-9.3%)] (P<0.001), and continued to be associated with better survival in both multivariable analysis and propensity-matched analysis. In the patients who received guideline therapy, median survival [24.9 (21.9-27.2) vs. 24.5 (21.7-28.1) months] and 5-year survival [14.9% (10.9-20.2%) vs. 20.1% (16.0-25.4%)] was not significantly different between patients who underwent induction (n=304) versus adjuvant (n=373) chemotherapy (P=0.444).

Conclusions: Guideline-concordant therapy for potentially resectable epithelioid mesothelioma is associated with significantly improved survival but used in a minority of patients. The timing of chemotherapy with surgery in this study did not have a significant impact on overall survival.

2023 Journal of Thoracic Disease. All rights reserved.
Impact of hyperthermic intrathoracic chemotherapy (HITHOC) during resection of pleural mesothelioma on patient survival. I.A. Elliott, H. He, N.S. Lui, et al. 2023;15(11):6140-6150. PubMed · Publisher · Free full text

Abstract

Background: Pleural mesothelioma (PM) is rare but portends a poor prognosis. Multimodal treatment, including aggressive surgical resection, may offer the best chance of treatment response and improved survival. Single-center studies suggest that hyperthermic intrathoracic chemotherapy (HITHOC) during surgical resection improves outcomes, but the impact of HITHOC on postoperative morbidity and survival has not been examined on a larger scale.

Methods: The National Cancer Database was queried for patients undergoing resection for PM from 2006-2017. Patients were excluded if staging or survival data was incomplete. After propensity-score matching, patients who underwent HITHOC were compared to patients who did not (case-control study). Perioperative outcomes and survival were analyzed.

Results: The final cohort consisted of 3,232 patients; of these, 365 patients underwent HITHOC. After propensity-score matching, receipt of HITHOC was associated with increased length of stay (12 vs. 7 days, P<0.001) and increased 30-day readmissions (9.9% vs. 4.9%, P=0.007), but decreased 30-day mortality (3.2% vs. 6.0%, P=0.017) and 90-day mortality (7.5% vs. 10.9%). Kaplan-Meier modeling demonstrated that HITHOC was associated with improved survival in the overall cohort (median 20.5 vs. 16.8 months, P=0.001). In multivariable analysis, HITHOC remained associated with improved overall survival [hazard ratio (HR) =0.80; 95% confidence interval (CI): 0.69-0.92; P=0.002], and this persisted in the propensity-matched analysis (HR =0.73; 95% CI: 0.61-0.88; P=0.001).

Conclusions: Using a large national database, we describe the impact of HITHOC on survival in patients with PM. Despite observed increased short-term morbidity, in multivariable analysis HITHOC was associated with an overall survival advantage for patients undergoing surgical resection of PM.

2023 Journal of Thoracic Disease. All rights reserved.
Utilizing residential histories to assess environmental exposure and socioeconomic status over the life course among mesothelioma patients. B. Liu, L. Niu, F.F. Lee. 2023;15(11):6126-6139. PubMed · Publisher · Free full text

Abstract

Background: Exposure misclassification based solely on the address at cancer diagnosis has been widely recognized though not commonly assessed.

Methods: We linked 1,015 mesothelioma cases diagnosed during 2011-2015 from the New York State Cancer Registry to inpatient claims and LexisNexis administrative data and constructed residential histories. Percentile ranking of exposure to ambient air toxics and socioeconomic status (SES) were based on the National Air Toxic Assessment and United States Census data, respectively. To facilitate comparisons over time, relative exposures (REs) were calculated by dividing the percentile ranking at individual census tract by the state-level average and subtracting one. We used generalized linear regression models to compare the RE in the past with that at cancer diagnosis, adjusting for patient-level characteristics.

Results: Approximately 43.7% of patients had residential information available for up to 30 years, and 96.0% up to 5 years. The median number of unique places lived was 4 [interquartile range (IQR), 2-6]. The time-weighted-average RE from all addresses available had a median of -0.11 (IQR, -0.50 to 0.30) for air toxics and -0.28 (IQR, -0.65 to 0.25) for SES. RE associated with air toxics (but not SES) was significantly higher for earlier addresses than addresses at cancer diagnosis for the 5-year [annual increase =1.24%; 95% confidence interval (CI): 0.71-1.77%; n=974] and 30-year (annual increase =0.36%; 95% CI: 0.25-0.48%; n=444) look-back windows, respectively.

Conclusions: Environmental exposure to non-asbestos air toxics among mesothelioma patients may be underestimated if based solely on the address at diagnosis. With geospatial data becoming more readily available, incorporating cancer patients' residential history would lead to reduced exposure misclassification and accurate health risk estimates.

2023 Journal of Thoracic Disease. All rights reserved.
Improving outcomes in malignant pleural mesothelioma in an integrated health care system. S. Ossowski, Y.Y. Hung, K. Banks, et al. 2022;14(9):3352-3363. PubMed · Publisher · Free full text

Abstract

Background: Malignant pleural mesothelioma (MPM) is a rare and aggressive tumor that should be managed by an experienced surgical and multidisciplinary group. Our objective was to determine the impact of proficient surgeons and MPM bi-disciplinary review on outcomes of patients with MPM.

Methods: Through this cohort study, electronic medical records of 368 adult patients with MPM from 1/1/2009 to 12/31/2020 were reviewed and compared before and after MPM surgeries were regionalized to specialized surgeons and bi-disciplinary review of MPM patient treatment options. We used the Kaplan-Meier method and log-rank tests to compare survival rates by period, by treatment type, and by stage. Patients were followed from cancer diagnosis date until they died or end of study follow-up, whichever occurred first. We also conducted Cox proportional hazards regression model to examine the overall survival (OS) with adjustments for age, histology, stage, and Charlson comorbidity index (CCI).

Results: Despite similar staging, more patients received any MPM directed treatment from 2015-2020 compared with those patients from 2009-2014. Specifically, there was an increase in patients who received pleurectomy/decortication (PD) from 2015-2020 compared to those who received PD in 2009-2014. Patients with similar age, CCI, stage, and histology had an increase in OS of 12 months with multimodality therapy (surgery, systemic therapy, +/- radiation) compared to those patients who received no treatment.

Conclusions: Consolidating mesothelioma surgery to a specialized surgical team and regular bi-disciplinary review of MPM cases to determine appropriate multimodality therapy, increases the incorporation of surgical treatments in the management of patients with MPM.

2022 Journal of Thoracic Disease. All rights reserved.
Proposal for a new local recurrence score in patients with recurrent malignant pleural mesothelioma. O. Lauk, T. Neuer, B. Battilana, et al. 2022;14(8):2835-2844. PubMed · Publisher · Free full text

Abstract

Background: Malignant pleural mesothelioma (MPM) is associated with high rates of local recurrence (LR) up to 75%. Second line treatment should be applied tailored to relapse pattern. We aimed to establish a new score for LR pattern with prognostic impact in this observational study of retrospective nature.

Methods: MPM patients with LR after surgery, verified by serial imaging during follow-up visits or biopsy were included in a retrospective analysis using a new local recurrence score (LRS). We divided the thoracic cavity into six sections and calculated the LRS according to the tumor burden. We assessed the impact on survival after recurrence using cox regression model.

Results: From 2001 until 2017, 128 consecutive MPM patients with LR who underwent macroscopic complete resection (MCR) by extrapleural pneumonectomy (EPP, n=61) or by (extended) pleurectomy/decortication [(E)PD, n=67], were included in the present analysis; 104 patients received second line therapy. Patients with chest wall (CW) recurrence had the shortest survival after recurrence (9 vs. 16 months, P=0.05) as well as patients with affected lymph nodes (LN) (9 vs. 17 months, P=0.02). In subgroup analysis, the (E)PD group had a significantly higher LRS (P≤0.001) despite a longer survival time after recurrence of 12.4 months (IQR, 6.45-20.32) compared to 9.3 months (IQR, 2.93-17.40, EPP group) (P=0.04). Patients with LRS ≤4 had a longer survival undergoing radiotherapy or local surgery for second line treatment whereas patients with LRS >4 only if they underwent chemotherapy.

Conclusions: LRS might be a useful prognostic tool in MPM patients with LR after multimodality therapy to guide second line treatment allocation.

2022 Journal of Thoracic Disease. All rights reserved.
Survival prognostic factors in unresectable/advanced primary thoracic sarcomas. J.R. Rodriguez-Cid, J.J. Juarez-Vignon Whaley, G. Sánchez-Domínguez, et al. 2022;14(9):3376-3385. PubMed · Publisher · Free full text

Abstract

Background: Primary thoracic sarcomas (PTS) including primary pulmonary and chest wall sarcomas (CWS), are aggressive lung malignancies with limited information specially in an advanced/unresectable setting. Unfortunately, prognostic factors for these malignancies are not well identified.

Methods: Retrospective cohort analysis of patients diagnosed with unresectable/advanced soft tissue PTS from a third level reference institute. Univariate and multivariate analysis performed via Cox-regression model. Progression-free survival (PFS) and overall survival (OS) analysis via Kaplan-Meier method.

Results: A total of 157 patients were identified, 55.4% female, mean age 51.8 years (range, 18-90 years), 19.1% tobacco exposure and 10.8% asbestos exposure. The most common performance status was Eastern Cooperative Oncology Group (ECOG) 1 (38.9%), most common clinical presentation cough (58.4%) and thoracic pain (55.4%). Undifferentiated sarcoma (37.6%) followed by synovial sarcoma (34.4%) were the most common histologies. Most patients received five chemotherapeutic cycles (37.6%), 57.3% of patients obtained a partial response and 61.1% an overall response rate (ORR). Median PFS was 9 months [95% confidence interval (CI): 8.717-9.283 months]. The multivariable analysis identified ECOG ≥2, a poorer response to chemotherapy (less number of chemotherapy cycles) and an increase Response Evaluation Criteria in Solid Tumors (RECIST) to be associated with a shorter progression-free period. Median OS was 11 months (95% CI: 10.402-11.958 months) with an ECOG ≥2 and a poorer response to chemotherapy (less number of chemotherapy cycles) associated with a shorter survival.

Conclusions: Age, gender, comorbidities, tobacco and asbestos exposure, clinical presentation and histopathological diagnosis are not useful prognostic factors in unresectable/advanced PTS, however, an adequate initial ECOG, RECIST and a better response to chemotherapy should be used as prognostic factors in the management of these tumors.

2022 Journal of Thoracic Disease. All rights reserved.
Thoracic surgery in Egypt. H. Elkhayat, H.H. Elsayed, W. Adel, et al. 2022;14(4):1282-1295. Review PubMed · Publisher · Free full text

Abstract

General thoracic surgery operations in Egypt are performed mainly by cardiothoracic surgeons and less oftenly by dedicated thoracic surgeons and general surgeons. This is mainly due to the relatively small number of thoracic surgeons in relation to population as only 210 cardiothoracic surgery specialists and 458 consultants are registered with the Egyptian Medical Syndicate (EMS) in a country with a population of more than 100 million people. Thoracic surgeons in Egypt are faced with a number of burdens, including the need to propagate the service to advanced technology infront of the obstacle of limited resources. Other burdens include higher incidence of TB, trauma and foreign body inhalation related to cultural backgrounds. More centres now are major video-assisted thoracic surgery (VATS) providing centres and others are specialized in more complex surgeries like complicated airway procedures and radical surgery for mesothelioma. As part of the international community, the COVID-19 pandemic has put more burdens on the thoracic surgery service as most centres have reduced their elective surgery workload to less than half of usual. Interestingly, the pandemic has allowed a self-referral screening programme with widespread Computed Tomography (CT) chest being performed among the population allowing thoracic surgeons to operate more on early stage lung cancer. The academic challenges for thoracic surgeons are even more with need for developing national databases. Nevertheless, thoracic surgeons in Egypt are optimistic regarding the future. The rising interest among the younger population will push training programs to meet the interests of enthusiastic junior surgeons. While the ancient history of thoracic surgery in Egypt seems to be extraordinary, the future perspectives promise to be more rewarding.

2022 Journal of Thoracic Disease. All rights reserved.
A narrative review of the health disparities associated with malignant pleural mesothelioma. D.C. Freudenberger, R.D. Shah. 2021;13(6):3809-3815. Review PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is a cancer of the mesothelial lining of the pleura that has traditionally been associated with asbestos exposure in an industrial setting. Asbestos usage has fortunately been banned or phased out in most industrialized countries resulting in its decline in countries such as the United States. Despite this, MPM continues to place significant burden on its affected patients resulting in overall poor prognosis and survival. Questions arise as to what factors, especially what health disparities, contribute to the disease's dismal prognosis. This article will present a narrative review of recent literature that identifies the impact age, sex, race, access to medical centers, and economics have on the diagnosis, treatment, and prognosis of MPM. As will be discussed, research has shown that factors including younger age, female sex, non-white race, private insurance, Medicare, and higher income have been associated with better survival in MPM. Whereas older age, male sex, white race, lack of insurance, and lower income are associated with worse survival. The identification of these and other health disparities related to MPM may allow for future research, clinical guidelines, and policies to be implemented to decrease the burden health disparities create in the diagnosis, treatment, and prognosis of patients with MPM.

2021 Journal of Thoracic Disease. All rights reserved.
Assessment of intrathoracic lymph nodes by FDG PET/CT in patients with asbestos-related lung cancer. N. Iga, H. Sonobe, D. Mizuno, et al. 2021;13(10):5925-5932. PubMed · Publisher · Free full text

Abstract

Background: This study explored the assessment of intrathoracic lymph node metastasis by 18F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography computed tomography (PET/CT) in patients with asbestos-related lung cancer (ARLC).

Methods: We retrospectively reviewed the data on 35 patients with ARLC who underwent preoperative FDG-PET/CT and surgical resection between January 2012 and December 2018. We collected medical information from medical records and imaging systems and examined the FDG uptake in each lymph nodal region resected by surgery and the presence or absence of pathological lymph node metastasis.

Results: Pathological lymph node metastases were detected in 14 (8.70%) of 161 nodal stations. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of FDG-PET/CT were 71.4% (10/14), 87.8% (129/147), 35.7% (10/28), 97.0% (129/133), and 86.3% (139/161), respectively. Six of the eight false-positive patients had bilateral accumulations, whereas all six true-positive patients had unilateral accumulation (P=0.006). On histopathological examination, the false-positive nodes showed disruption of lymphoid follicles in the cortex, infiltration of histiocyte-like cells in the medulla, fibrous micronodules, and severe anthracosis.

Conclusions: PET/CT scans of patients with ARLC showed comparable sensitivity and specificity to those of PET/CT scans of patients with conventional lung cancer reported in the literature. Many false-positive cases also showed bilateral symmetric accumulation. This method can be used to evaluate lymph node involvement in lung cancer.

2021 Journal of Thoracic Disease. All rights reserved.
BRCA-associated protein 1 (BAP1) and miR-31 combination predicts outcomes in epithelioid malignant pleural mesothelioma. A. Murrone, L. Cantini, F. Pecci, et al. 2021;13(10):5741-5751. PubMed · Publisher · Free full text

Abstract

Background: Malignant pleural mesothelioma (MPM) is an aggressive disease, with few available treatment options. Identification of novel prognostic and predictive biomarkers is a priority. In MPM patients, BRCA-associated protein 1 (BAP1) alterations are detected in about 60% of cases and miR-31 seems to be involved in BAP1 regulation at post-transcriptional level. The aim of this study was to evaluate the interaction between BAP1 and miR-31 in MPM and their prognostic role in MPM.

Methods: The expression of BAP1 and miR-31 was analyzed in tissues of 55 MPM patients treated with first-line chemotherapy. Overall survival (OS) and progression-free survival (PFS) were assessed by Kaplan-Meier method and Log-rank test was used to investigate differences among subgroups. Multivariate Cox regression analysis was used to evaluate independent predictors of survival.

Results: In the whole cohort, loss of BAP1 was associated with a significant improvement in OS, but not in PFS. Lower miR-31 levels were detected in epithelioid MPM (e-MPM) compared to the non-epithelioid subtypes and resulted associated with BAP1 loss. By looking at the e-MPM subgroup, loss of BAP1 was not able to predict clinical outcome. Conversely, miR-31 levels were significantly associated with PFS (P=0.028), but not with OS (P=0.059). By combining the two biomarkers, e-MPM patients with BAP1 loss/low miR-31 levels showed a better prognosis compared to the ones with BAP1 retained/high miR-31 levels (median OS 22.6 vs. 17.0 months, P=0.017 and median PFS 8.7 vs. 5.1 months, P=0.020). The BAP1 and miR-31 combination was confirmed at multivariate analysis as an independent prognostic factor for e-MPM patients.

Conclusions: In this preliminary study, we found that the prognostic stratification of e-MPM patients may be improved by simultaneously assessing of BAP1 status and miR-31 levels. The two-biomarker score is useful to identify a subgroup of e-MPM tumors characterized by BAP1 retained and high miR-31 levels with worse clinical outcome.

2021 Journal of Thoracic Disease. All rights reserved.
Epidemiology, diagnosis and treatment of the malignant pleural mesothelioma, a narrative review of literature. S.O. Schumann, G. Kocher, F. Minervini. 2021;13(4):2510-2523. Review PubMed · Publisher · Free full text

Abstract

The malignant pleural mesothelioma is a very aggressive tumor which is arising from mesothelial cells and is associated with asbestos exposure. It is a heterogeneous cancer that shows a complex pattern of molecular changes, including genetic, chromosomic, and epigenetic abnormalities. The malignant pleural mesothelioma is characterized by a silent and slow clinical progression with an average period of 20-40 years from the asbestos exposure phase to the start of the symptoms. Unfortunately, to date, the therapeutic options are very limited, especially if the tumor is detected late. This narrative review provides an extended overview of the present evidence in the literature regarding the epidemiology, diagnostic pathways and treatment approaches of the malignant pleural mesothelioma. The treatment of mesothelioma has evolved slowly over the last 20 years not only from a surgical point of view but also radiotherapy, chemotherapy and immunotherapy play nowadays a key role. Several surgical strategies are available ranging from extrapleural pneumonectomy to cytoreductive surgery but a multidisciplinary approach seems to be mandatory because a single approach has not proved to date to be resolutive. New non-surgical treatment options appear to be promising but the results have to be taken in account with caution because clear evidence with high-quality studies is still lacking.

2021 Journal of Thoracic Disease. All rights reserved.
Long-term outcomes after lung-sparing surgery for epithelial mesothelioma. C. Breda, S. Furia, G. Lucchini, et al. 2021;13(11):6283-6293. PubMed · Publisher · Free full text

Abstract

Background: This observational study evaluates retrospectively the long-term outcomes after pleurectomy/decortication for pleural mesothelioma, with and without the resection/reconstruction of diaphragm and pericardium.

Methods: Data from 155 consecutive patients undergoing lung-sparing surgery for epithelial pleural mesothelioma were reviewed. Selection criteria for surgery were cT1-3, cN0-1, good performance status, age <80 years. Perioperative Pemetrexed-Platinum regimen was administered as induction in 101 cases (65.2%) and as adjuvant treatment in 54 cases (34.8%). Extended pleurectomy/decortication was performed in 87 cases (56.12%). In 68 patients (43.87%) standard pleurectomy/decortication was performed without resection/reconstruction of diaphragm and pericardium, when tumour infiltration was deemed absent after intraoperative frozen section. The log-rank test and Cox regression model were used to assess the factors affecting overall survival and recurrence free survival.

Results: Median follow-up was 20 months. The 2- and 5-year survival rate was 60.9% and 29.2% with a median survival of 34 months. An improved survival was observed when standard pleurectomy/decortication was carried out (P=0.007). A significant impact on survival was found comparing the TNM-stages (P=0.001), pT (P=0.002) and pN variables (P=0.001). Multivariate analysis identified the pN-status (P=0.003) and standard pleurectomy/decortication (P=0.017) as predictive for longer survival. The recurrence-free survival >12 months was strongly related to the overall survival (P<0.001). The macroscopic complete resection (P=0.001), TNM-stage (P=0.003) and pT-status (P=0.001) are related to relapse.

Conclusions: Within multimodal management of pleural mesothelioma, lung-sparing surgery is a valid option even with more conservative technique. A benefit for a longer survival was observed in the early stage of disease, with pN0 and when pleurectomy/decortication is carried out, preserving diaphragm and pericardium. Recurrence is not affected by the type of surgery, and a recurrence-free interval >12 months is predictive of an increased survival when the macroscopic complete resection is achieved.

2021 Journal of Thoracic Disease. All rights reserved.
The expression patterns and prognostic significance of pleckstrin homology-like domain family A (PHLDA) in lung cancer and malignant mesothelioma. C.M. Baldavira, J. Machado-Rugolo, T.G. Prieto, et al. 2021;13(2):689-707. PubMed · Publisher · Free full text

Abstract

Background: Pleckstrin homology domain family A (PHLDA) genes play important roles in cancer cellular processes, including inhibiting Akt activation, repressing growth factor signaling, inhibiting the negative feedback of EGFR/ErbB2 signaling cells, and inducing apoptosis. However, the prognostic significance of PHLDA in non-small cell lung cancer (NSCLC) and malignant pleural mesothelioma (MM) remains unclear. The present study investigates the associations between PHLDA expression patterns and their prognostic value in lung adenocarcinoma (LUAD) and MM.

Methods: We analyzed PHLDA family members at the genomic level in silico to explore their mRNA expression pattern and predictive significance in LUAD and MM. We then created a PHLDA-drug interaction network and a protein-protein interaction (PPI) network using different databases. Finally, we immunohistochemically assessed the protein expression of each PHLDA family member on tissue microarrays (TMAs) in both LUAD and MM cohorts with long-term follow-up.

Results: While PHLDA1 mRNA expression in both LUAD and MM was lower than that of normal tissue, PHLDA2 mRNA was significantly overexpressed in LUAD, and PHLDA3 mRNA was overexpressed in MM. In NSCLC, both low PHLDA1 mRNA expression and high PHLDA3 mRNA expression correlated with worse overall survival (OS) (P<0.01), whereas high PHLDA2 mRNA expression was associated with better OS (P<0.01). In MM, patients presenting high PHLDA1 and PHLDA2 mRNA expression had poor OS (P=0.01 and P<0.01, respectively). In addition, the PHLDA-drug interaction network indicated that several common drugs could potentially modulate PHLDA expression, and the PPI network suggested that PHLDA1 interacts with Notch family members, whereas PHLDA3 interacts with TP53. Our results also showed that the expression of PHLDA2 and PHLDA3 was significantly higher in LUAD and MM than that of PHLDA1 (P<0.05) and was associated with the risk of death. While patients with PHLDA2 >85.09 cells/mm2 had a low risk of death (P=0.01) and a median survival time of 48 months, those with PHLDA3 <70.38 cells/mm2 had a high risk of death (P=0.03) and a median survival time of 34 months.

Conclusions: We shed light on the role of the PHLDA family as promising predictive biomarkers and potential therapeutic targets in LUAD and MM.

2021 Journal of Thoracic Disease. All rights reserved.
A multidisciplinary approach for the diagnosis of benign asbestos pleural effusion: a single-center experience. W. Luo, Y. Zeng, P. Shen, et al. 2020;12(8):4338-4346. PubMed · Publisher · Free full text

Abstract

Background: There is little detailed information regarding benign asbestos pleural effusion (BAPE). It is frequently misdiagnosed because of lack of a standardized diagnostic approach and criteria. The present study aimed to better characterize BAPE and outline a diagnostic approach for this disease.

Methods: Complete clinical data of 11 consecutive patients with BAPE were prospectively collected and analysed. A multidisciplinary team (MDT) was involved in discussing the suspected cases of BAPE. The team was comprised of thoracic physicians, radiologists and pathologists. A multidisciplinary practical diagnostic approach for BAPE was introduced.

Results: Six patients had respiratory symptoms, but another 5 were asymptomatic. All the patients had an asbestos exposure and the median duration was 23.9 years (rang, 12-36 years). The median level of lactate dehydrogenase (LDH), adenosine deaminase (ADA), proteins and carcinoembryonic antigen (CEA) in the pleural fluid (PF) were 221.4 U/L (range, 189.8-11,325 U/L), 21 U/L (rang, 14-247 U/L), 48.3 g/dL (range, 35.2-53.2 g/dL) and 3.46 mg/mL (range, 0.84-4.54 mg/mL), respectively. Five patients had pleural plaques, 2 had diffuse pleural thickening (DPT), 1 had asbestosis, and 1 had round atelectasis. The pleural biopsy specimens showed a benign fibrotic pleura in all case. The symptoms and pleural pulmonary radiologic findings remained stable during the follow-up.

Conclusions: BAPE is diagnosed by exclusion. A suspected diagnosis of BAPE with an asbestos exposure should be considered, especially with the presence of pleural plaques, and/or DPT, and rounded atelectasis. The MDT-based diagnostic approach may reduce misdiagnosis.

2020 Journal of Thoracic Disease. All rights reserved.
Quantitation and predictors of short-term mortality following extrapleural pneumonectomy, pleurectomy/decortication, and nonoperative management for malignant pleural mesothelioma. C. Wright, V. Verma, A.R. Barsky, et al. 2020;12(11):6476-6493. PubMed · Publisher · Free full text

Abstract

Background: For malignant pleural mesothelioma (MPM), the benefit of resection, as well as the optimal surgical technique, remain controversial. In efforts to better refine patient selection, this retrospective observational cohort study queried the National Cancer Database in an effort to quantify and evaluate predictors of 30- and 90-day mortality between extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D), as well as nonoperative management.

Methods: After applying selection criteria, cumulative incidences of mortality by treatment paradigm were graphed for the unadjusted and propensity-matched populations, as well as for six a priori age-based intervals (≤60, 61-65, 66-70, 71-75, 76-80, and ≥81 years). The interaction between age and hazard ratio (HR) for mortality between treatment paradigms was also graphed. Cox multivariable analysis ascertained factors independently associated with 30- and 90-day mortality.

Results: Of 10,723 patients, 2,125 (19.8%) received resection (n=438 EPP, n=1,687 P/D) and 8,598 (80.2%) underwent nonoperative management. The unadjusted 30/90-day mortality for EPP, P/D, and all operated cases was 3.0%/8.0%, 5.4%/14.1%, and 4.9%/12.8%, respectively. There were no short-term mortality differences between EPP and P/D following propensity-matching, within each age interval, or between age subgroups on interaction testing (P>0.05 for all). Nonoperative patients had a crude 30- and 90-day mortality of 9.9% and 24.6%, respectively. Several variables were identified as predictors of short-term mortality, notably patient age (HR 1.022, P<0.001), Charlson-Deyo comorbidity index (HR 1.882, P<0.001), receipt of treatment at high-volume centers (HR 0.834, P=0.032) and induction chemotherapy (HR 1.735, P=0.025), among others. The patient (yearly) incremental increase in age conferred 2.0% (30 day) and 2.2% (90 day) increased risk of mortality (P<0.001).

Conclusions: Quantitative estimates of age-associated 30- and 90-day mortality of EPP and P/D should be considered when potentially operable patients are counseled regarding the risks and benefits of resection.

2020 Journal of Thoracic Disease. All rights reserved.
Surgical staging and resection of malignant pleural mesothelioma. L.B. Brown, F. Corl, S.H. Blackmon. 2020;12(12):7467-7480. PubMed · Publisher · Free full text
Three tumor markers for improved efficacy in the management of patients with malignant pleural mesothelioma. A. Nakamura, T. Takuwa, M. Hashimoto, et al. 2020;12(11):6712-6721. PubMed · Publisher · Free full text

Abstract

Background: Evaluation of tumor markers may facilitate follow-up of malignant pleural mesothelioma (MPM). We aimed was to evaluate the value of tumor markers for monitoring and predicting recurrence in patients with MPM.

Methods: In total, 152 patients who underwent curative-intent surgery after induction chemotherapy for MPM between July 2004 and December 2017 were retrospectively reviewed. Preoperative and postoperative (≤3 months after surgery) levels of soluble mesothelin-related peptide (SMRP), cytokeratin 19 fragment (Cyfra21-1), and tissue polypeptide antigen (TPA) and rates of recurrence and non-recurrence were evaluated. Factors associated with recurrence-free survival (RFS) were assessed using the Kaplan-Meier method and Cox proportional hazards model.

Results: Of the 152 patients, the positive rates of preoperative SMRP, Cyfra21-1, and TPA, levels were 26.7%, 8.6%, 9.6%, respectively; the respective postoperative levels were 4.0%, 6.3%, and 6.5%; the respective levels in patients with recurrence were 39.3%, 31.4%, 28.6%; the respective levels in patients with no recurrence were 3.7%, 0.0%, 3.8%. Nearly half (45.2%) of the patients with recurrence exhibited an increase in one or more tumor marker levels. Multivariate analysis revealed that the preoperative positive rates of one or more of the three tumor markers (hazard ratio: 1.8, 95% confidence interval: 1.1-2.8; P=0.02) were independent significant predictors of recurrence.

Conclusions: The positive rates of SMRP, Cyfra21-1, and TPA in recurrence-free patients were extremely low, with high specificity. Preoperative levels of SMRP, Cyfra21-1, and TPA, which identified patients with a high risk for recurrence, could improve management of patients with MPM.

2020 Journal of Thoracic Disease. All rights reserved.
Ultrasound-guided percutaneous needle biopsy skill for peripheral lung lesions and complications prevention. H. Zhang, Y. Guang, W. He, et al. 2020;12(7):3697-3705. PubMed · Publisher · Free full text

Abstract

Background: To investigate puncture skills and complications prevention in ultrasound-guided percutaneous needle biopsy for peripheral lung lesions.

Methods: Ninety-two peripheral lung lesions in 92 patients, detected via computed tomography (CT) and also visible on ultrasound, were retrospectively analyzed. All patients underwent percutaneous peripheral lung lesion needle biopsy under traditional ultrasound or contrast enhanced ultrasound (CEUS) guidance paying attention to avoiding necrotic areas and large blood vessels. All the specimens were examined histopathologically. Preprocedure all 92 lesions were performed by traditional ultrasonography to evaluate the size, the echogenecity, liquefaction areas and blood flow on color Doppler imaging, some of which were performed by CEUS for evaluating non-enhanced necrosis areas, contrast agent arrival time (AT) and characteristics of blood perfusion.

Results: The histopathologic results of all 92 lesions were as follows: 67 malignant tumors (including 28 adenocarcinomas, 19 squamous cell carcinomas, 6 bronchoalveolar carcinomas, 5 small cell carcinomas, 5 metastatic cancers, 3 poorly differentiated cancers and 1 malignant mesothelioma), 20 benign lesions (including 9 pneumonia, 6 inflammatory pseudotumors and 5 tuberculomas), 5 undetermined lesions. Of 52 lesions by CEUS guidance, 7 lesions showed enhancement in the pulmonary arterial-phase (including 6 pneumonia and 1 malignant tumors), 45 lesions showed enhancement in the bronchial artery phase (including 37 malignant tumors, 3 inflammatory pseudotumors, 4 tuberculomas and 1 undetermined lesion). According to needle insertion angle along linear path, a total of 92 lesions were divided into two groups, 49 lesions at an angle of 70°-80° needle insertion and 43 lesions at an angle of 80°-90° needle insertion. In the study, linear and non-linear two puncture paths were used, we first tried to puncture along linear path in all lesions, if an attempt to insert into the lesions failed due to be blocked by the ribs and then changed to puncture along non-linear path instead. The success rate of biopsy procedure along linear puncture was significantly higher at an angle of 80°-90°group (93.0% vs. 20.4%, P<0.01), and the adoption rate of non-linear path biopsy for solving the puncture needle blocked by the ribs was significantly higher at angle of 70°-80°group (79.6% vs. 7.0%, P<0.01). Of 52 lesions by CEUS guidance, 27 (51.9%) showed non enhanced necrosis areas on CEUS, only 5 showed liquefaction necrosis areas on gray-scale ultrasound. Of 40 lesions by traditional ultrasound guidance, 4 showed necrosis areas on gray-scale ultrasound. There were no significant differences in lesion size, the average number of biopsy attempts and complication rates between CEUS guidance group and traditional ultrasound guidance group (P>0.05), the pathological confirmation rate in CEUS guidance group was higher than that in traditional ultrasound guidance group, but without significant difference (98.1% vs. 90.0%, P>0.05). Of all 92 cases, 3 cases (3.3%) had mild pneumothorax and 4 cases (4.3%) had hemoptysis.

Conclusions: In ultrasound-guided needle biopsy for peripheral lung lesions, using a combination of linear and non-linear puncture techniques and keeping away from necrotic areas and large blood vessels, may help to increase the success rate and reduce the incidence of complications further.

2020 Journal of Thoracic Disease. All rights reserved.

2010s

Biomarkers in malignant pleural mesothelioma: current status and future directions. T. Ahmadzada, G. Reid, S. Kao. 2018;10(Suppl 9):S1003-S1007. Editorial · Comment PubMed · Publisher · Free full text

Summary

This invited editorial commented on a review of mesothelioma biomarkers by Sun, Vaynblat and Pass (Ann Transl Med 2017). The authors described malignant pleural mesothelioma (MPM) as an uncommon, aggressive tumour associated with asbestos exposure. It is often diagnosed late, typical survival is around 1 year, and treatment options are limited. They summarised evidence on blood-based markers. Soluble mesothelin (SMRP) was the only clinically validated, FDA-approved blood biomarker, but a meta-analysis reported 32% sensitivity at 95% specificity. Meta-analyses reported osteopontin sensitivity of 65% and specificity of 81% (360 cases), and fibulin-3 sensitivity of 62% at 82% specificity (468 cases). A hyperacetylated isoform of HMGB1 distinguished MPM patients from asbestos-exposed and healthy controls in one study. SMRP, osteopontin and HMGB1 were associated with poor prognosis but had not been prospectively validated. The authors also discussed inflammation-based scores and microRNAs, including a six-miRNA signature that predicted survival beyond 20 months with 92.3% accuracy after extrapleural pneumonectomy and 71.9% after pleurectomy/decortication. No predictive biomarkers had been recommended for clinical practice, including for bevacizumab or nintedanib. PD-L1 was described as a robust prognostic marker, and one retrospective study suggested an association with pembrolizumab response. The authors concluded that promising biomarkers required independent validation, that international collaboration was important, and that more research should focus on predictive biomarkers.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.
Biomarkers in the prevention and follow-up of workers exposed to asbestos. R. Foddis, A. Bonotti, S. Landi, et al. 2018;10(Suppl 2):S360-S368. Review PubMed · Publisher · Free full text

Abstract

Although in most developed countries the use of asbestos is banned, there is still a consistent portion of the world where asbestos extraction, trading and manufacturing of asbestos-made products is largely diffuse. Worldwide, hundreds of millions of people are at risk of developing an asbestos caused disease because of occupational, environmental or domestic exposure. The WHO estimates that asbestos is responsible for more than 100,000 deaths yearly. This scenario has prompted the research on biomarkers potentially useful for early diagnosis, prognosis and preventive programs on exposed population as well. Here we reviewed the up-to-date literature on this field of research highlighting that along with mesothelin and osteopontin (OPN), some more recently investigated molecules, such as high mobility group box 1 (HMGB1) protein, fibulin-3 and some miRNAs showed very promising. Most of the carried-out studies showed an interesting diagnostic and prognostic performance of some biomarkers, but since they usually lack adequate either specificity or sensitivity, their use in screening or in preventive programs is still not recommended on a routine basis. However, this review suggests the need for more reliable experimental design involving larger population and preferring longitudinal screening of asbestos exposed individuals rather than a single baseline assessment investigation. In addition, given their better diagnostic accuracy, the use of panels including several biomarkers is highly recommended.
Clinical diagnosis of malignant pleural mesothelioma. A. Bianco, T. Valente, M.L. De Rimini, et al. 2018;10(Suppl 2):S253-S261. Review PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is a tumour which, despite progress in diagnostic procedures and biomolecular research, has poor prognosis. Symptoms reflect extension of disease and include shortness of breath and chest pain. Unexplained pleural effusion and pleural pain in patients exposed to asbestos should raise the suspicion of MPM. MPM diagnosis requires imaging procedures X-ray and computed tomography (CT) scans; magnetic resonance imaging (MRI) better defines the extension of the tumor while PET scanning provides additional information on metabolic activity, metastases, and response to treatment. Thoracoscopic biopsy remains the most appropriate procedure for definitive diagnosis of mesothelioma. Multimodality treatment including surgery, chemotherapy and radiotherapy has been associated with a better survival in selected patients. Clinical translational research including new approaches targeting immune-checkpoints is opening new horizons which may lead to personalised treatments.
Endoscopic diagnosis and management of pleural effusion in malignant pleural mesothelioma. P. Ceruti, S. Lonni, F. Baglivo, et al. 2018;10(Suppl 2):S269-S275. Review PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is an asbestos-related aggressive tumor, that requires proper diagnosis and management. Symptoms are nonspecific and chest computed tomography (CT) and chest ultrasound (US) are important radiological tools in the initial workup to identify early pathological signs. Performing a medical thoracoscopy (MT) is essential for a definitive diagnosis of MPM. The procedure, integrated with a prior US, allows a global evaluation of the pleural cavity and the execution of multiple targeted biopsies, with low risk of complications. Some different endoscopic patterns are recognized. Thoracoscopic biopsies provide enough material to allow a thorough pathological and immunohistochemical characterization. The presence of extensive pleural adhesions and critical patient conditions are the only absolute contraindications. The clinical course of MPM is characterized by chronic symptoms such as chest pain and progressive dyspnea, the latter caused mainly by recurrent pleural effusion. Palliative interventions are required in order to relieve symptoms and improve the quality of life (QoL). These include thoracentesis, pleurodesis and the placement of an indwelling pleural catheter.
Epidemiology of malignant mesothelioma in Italy: surveillance systems, territorial clusters and occupations involved. A. Marinaccio, A. Binazzi, M. Bonafede, et al. 2018;10(Suppl 2):S221-S227. PubMed · Publisher · Free full text

Abstract

Background: As a legacy of the large asbestos consumption until the definitive ban in 1992, Italy is currently suffering a severe epidemic of asbestos related diseases. The aim of this paper is to describe the surveillance system for mesothelioma incidence and to provide evidences regarding the occurrence of the disease in Italy and the circumstances of asbestos exposure.

Methods: Italian National Register of Malignant Mesotheliomas (ReNaM) is a permanent surveillance system of mesothelioma incidence, with Regional Operating Centres (CORs) active in each Italian region, identifying incident malignant mesothelioma (MM) cases from health care structures. Occupational history, lifestyle habits and residential history are obtained using a standardised questionnaire, administered by a trained interviewer, to the subject or to the next of kin. Descriptive epidemiological figures, occupations involved in exposures and territorial maps of MM cases have been produced.

Results: At December 2016, ReNaM has collected 27,356 MM cases for the incidence period between 1993 and 2015. The modalities of exposure to asbestos have been investigated for 21,387 (78%) and an occupational exposure has been defined for around 70% of interviewed cases (14,818). Non-occupational exposure is still relevant with 4.9% and 4.4% of cases for which respectively a familial exposure (due to the cohabitation with an occupational exposed subject) and an environmental exposure (due to the residence near a contaminated site) has been detected.

Discussion: The epidemiological surveillance of MM incident cases, by the means of a national register for estimating the occurrence of the disease and identifying the circumstances of asbestos exposure, is a relevant tool for preventing asbestos exposure, for supporting the effectiveness of insurance system and for estimating reliable epidemiological figures.
Exposure to asbestos: past, present and future. E. Pira, F. Donato, L. Maida, et al. 2018;10(Suppl 2):S237-S245. Review PubMed · Publisher · Free full text

Abstract

This paper summarises the past, present and future of asbestos exposure. The future scenarios as to the mesothelioma incidence in countries, where asbestos has been banned, are discussed.
Health surveillance for former asbestos exposed worker: a specific programme developed in an Italian region. E. Chellini, F. Battisti, A. Cristaudo, et al. 2018;10(Suppl 2):S383-S389. PubMed · Publisher · Free full text

Abstract

Asbestos-related diseases usually have a long latency since first exposure and this legitimates a health surveillance programme addressed to asbestos workers after the cessation of their occupational exposure. After a brief history of health surveillance initiatives performed in Italy as well as in other countries, we describe a regional programme for former asbestos-exposed workers, focusing on organizational features. A regional group of experts defined its operational and economical aspects. The Regional Council supported the whole programme, making it free of charge for all subjects who fulfil the predefined enrolment criteria (being resident in the region, being younger than 80 years old with cessation of occupational asbestos exposure within the last 30 years). The programme activities are classified in two levels: a first level for a basic health evaluation and a second level for in-depth analyses. In order to guarantee an homogeneous delivery in the whole region, the programme has to be performed by public health services with a quality control of activities. The involvement of specific public health services and the cooperation of social stakeholders are expected to play a major role in overcoming still open critical issues, such as the lack of programme existence awareness and adhesion, the correct stratification of subjects for the follow-up, and the real homogeneous delivery of the health surveillance in whole region.
Imaging of malignant pleural mesothelioma: it is possible a screening or early diagnosis program?-a systematic review about the use of screening programs in a population of asbestos exposed workers. F. Falaschi, C. Romei, S. Fiorini, et al. 2018;10(Suppl 2):S262-S268. Review PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) in an uncommon neoplasia with high mortality rate, mostly related to professional asbestos exposure. Clinical manifestations are not specific so that diagnosis is performed at advanced stage and screening protocols are not feasible now. On the other hand, asbestos-exposed workers have a high incidence of developing lung cancer. Low-dose computed tomography (LDCT) is a volumetric acquisition technique with high spatial resolution and a low dose exposure; it is used in many trials to detect lung tumours at an early stage in screening protocols, reducing mortality rate in smoker subjects. In recent papers, the possibly role of lung cancer screening was evaluated and recommended also in subjects exposed to asbestos. This article summarizes previous and present clinical trials validated for lung cancer screening, to discuss the possibility of early diagnosis or screening programs in a population of asbestos exposed workers by LDCT.
Molecular markers and new diagnostic methods to differentiate malignant from benign mesothelial pleural proliferations: a literature review. R. Bruno, G. Alì, G. Fontanini. 2018;10(Suppl 2):S342-S352. Review PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is an aggressive tumor associated with asbestos exposure. Histopathological analysis of pleural tissues is the gold standard for diagnosis; however, it can be difficult to differentiate malignant from benign pleural lesions. The purpose of this review is to describe the most important biomarkers and new diagnostic tools suggested for this differential diagnosis. There are many studies concerning the separation between MPM and benign pleural proliferations from both pleural tissues or effusions; most of them are based on the evaluation of one or few biomarkers by immunohistochemistry (IHC) or enzyme-linked immunosorbent assays (ELISAs), whereas others focused on the identification of MPM signatures given by microRNA (miRNA) or gene expression profiles as well as on the combination of molecular data and classification algorithms. None of the reported biomarkers showed adequate diagnostic accuracy, except for p16 [evaluated by fluorescent in situ hybridization (FISH)] and BAP1 (evaluated by IHC), both biomarkers are recommended by the International Mesothelioma Interest Group guidelines for histological and cytological diagnosis. BAP1 and p16 showed a specificity of 100% in discerning malignant from benign lesions because they are exclusively unexpressed or deleted in MPM. However, their sensitivity, even when used together, is not completely sufficient, and absence of their alterations cannot confirm the benign nature of the lesion. Recently, the availability of new techniques and increasing knowledge regarding MPM genetics led to the definition of some molecular panels, including genes or miRNAs specifically deregulated in MPM, that are extremely valuable for differential diagnosis. Moreover, the development of classification algorithms is facilitating the application of molecular data for clinical practice. Data regarding new diagnostic tools and MPM signatures are absolutely promising; however, before their application in clinical practice, a prospective validation is necessary, as these approaches could surely improve the differential diagnosis between malignant and benign pleural lesions.
Quantification of pleural plaques by computed tomography and correlations with pulmonary function: preliminary study. Y.K. Cha, J.S. Kim, J.H. Kwon. 2018;10(4):2118-2124. PubMed · Publisher · Free full text

Abstract

Background: The aims of this study were to quantify pleural plaque volumes (PPVs) by computed tomography (CT) and investigate relations between PPV and pulmonary function after excluding other factors that might affect pulmonary function.

Methods: Twenty-six subjects with pleural plaques and pulmonary function test (PFT) results among 1,544 subjects that registered with the Korea Environment Corporation for asbestos damage relief from January 2011 to December 2015 were included. Subjects with CT evidence of lung diseases and/or previous surgery were excluded. PPVs were measured by tracing the outlines of all pleural plaques on CT images. Patients were allocated to three groups by PPV, as follows, <10, 10-20, or ≥20 mL, and the PFT results of these groups were analyzed and compared. Simple linear regression analysis and multiple regression analysis were used to evaluate correlations between PPV and PFT variables.

Results: No significant relationship was found between total PPV and pulmonary function indices or between PPV groups and PFT results (P>0.05). However, forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and diffusing capacity of the lung for carbon monoxide (DLCO) values in the higher PPV group (≥20 mL) tended to be lower, indicating a restrictive pattern of pulmonary function.

Conclusions: We quantified PPV on CT and found out higher PPV tended to exhibit a restrictive pattern. However, pleural plaques alone were not found to be significantly associated with pulmonary function.
Serum mesothelin and other biomarkers: what have we learned in the last decade?. A. Cristaudo, A. Bonotti, G. Guglielmi, et al. 2018;10(Suppl 2):S353-S359. Review PubMed · Publisher · Free full text

Abstract

In the last decade there is been much interest in noninvasive, economic and well-accepted diagnostic tests for screening of subjects exposed to asbestos, and in patients with malignant pleuric mesothelioma (MPM) for diagnosis or monitoring response to treatment. Several biomarkers have been suggested as tools for screening and early diagnosis of MPM. Currently, in patients with MPM, have been reported high levels of soluble mesothelin-related peptides (SMRP), plasmatic osteopontin (pOPN), vimentin, fibulin-3 and many others as promising marker for diagnosis, even their use in prevention monitoring is still discussed. In this type of disease, a key role could be played by miRNAs, which expression has been investigated in a large series of MPM to examine new pathways useful in diagnosis, prognosis and therapy. An altered expression of some proteins has been reported, useful as biomarkers, in comparative proteomic analysis of malignant pleural mesothelioma. New promising markers are nowadays under study and alone or better in combination, they'll be very helpful in diagnosing, monitoring mesothelioma patients or for screening of risk groups.
The genetic susceptibility in the development of malignant pleural mesothelioma. O. Melaiu, F. Gemignani, S. Landi. 2018;10(Suppl 2):S246-S252. Review PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is a cancer of the pleural cavity whose main risk factor is exposure to asbestos. However, it has been shown that only a minority of exposed people develops MPM. In fact, the incidence among professionally exposed workers was shown to vary between 0.5% and 18.0%. Various hints suggested that other important cofactors could play a role, in particular the genetic susceptibility. Impressive is the case of Cappadocians families exposed to erionite and affected by an "epidemic" of MPM with about half of the inhabitants dying for the disease. However, no results for a "Cappadocia" gene of susceptibility to MPM have been obtained yet and more studies are needed. Among asbestos-exposed workers, several studies reported familial cases of MPM, suggesting that heredity could be important in the tumor development. However, large studies on familial clusters showed only weak increased risks that could be attributable also to indirect exposures in a contaminated household. Moreover, the risk of developing MPM is increased of a limited extent among people exposed to asbestos with a positive history of familial cancers. A particular is represented by carriers of germline mutations within BAP1 gene. In families and in animal models, mutations within BAP1 are strongly predisposing to develop MPM. However, also other types of cancer (such as uveal melanoma) are present, thus BAP1 mutations are considered as responsible for a hereditary form of a multi-cancer syndrome. In any case, among sporadic MPM, the prevalence of germline BAP1 mutations is negligible. Finally, genetic studies highlighted the presence of low-risk susceptibility alleles, such as those within XRCC3, NAT2 or GSTM1. Two different genome-wide association studies could not find positive associations reaching the genome-wide statistical significance threshold, however, both were concordant in showing a weak signal within the SDK1 gene region. Overall, it could be concluded that, as for other types of sporadic cancers, the susceptibility to develop MPM following asbestos exposure is modulated moderately by the individual genetic background. Further studies on larger series could help in a better characterization of more genes predisposing to MPM, being this tumor a rare disease.
The pathological and molecular diagnosis of malignant pleural mesothelioma: a literature review. G. Alì, R. Bruno, G. Fontanini. 2018;10(Suppl 2):S276-S284. Review PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM), an asbestos-induced tumor, represents significant diagnostic challenges for pathologists. Its histological diagnosis is stepwise and should be based on morphological assessment, supported by clinical and radiological findings, and supplemented with immunohistochemistry (IHC) and, more recently, molecular tests. The main diagnostic dilemmas are the differential diagnoses with benign mesothelial proliferations and other pleural malignant tumors. The present review is an update regarding the morphological, immunohistochemical, and molecular features with respect to MPM diagnosis. Data sources include a survey of the biomedical literature from PubMed (http://www.ncbi.nlm.nih.gov/pubmed) and textbooks focusing on the pathological diagnosis of MPM and associated immunohistochemical and molecular markers. The histological findings of MPM could facilitate its diagnosis and provide important prognostic information. The immunohistochemical approach should rest on the application of a panel including positive (mesothelial-related) and negative markers with greater than 80% sensitivity and specificity, which need to be selected based on morphology and clinical information. Moreover, in challenging cases, fluorescent in situ hybridization (FISH) testing for the p16 deletion and IHC to evaluate the loss of BRCA1-associated protein 1 (BAP1) expression could be useful in distinguishing benign from malignant pleural proliferations.
Pleural and peritoneal mesotheliomas in the Friuli Venezia Giulia register: data analysis from 1995 to 2015 in Northeastern Italy. F. D'Agostin, P. De Michieli, C. Chermaz, et al. 2017;9(4):1032-1045. PubMed · Publisher · Free full text

Abstract

Background: The Friuli Venezia Giulia Mesothelioma Register contains a case-list of 1,109 mesotheliomas (1,034 pleural, 75 peritoneal) during 1995-2015. Exposure data are available for almost all cases. The aim was to assess mesothelioma incidence in the Region, an area with several shipyards, and to investigate determinants of mesothelioma latency among occupational cases.

Methods: Incidence rates were calculated. Univariate and multivariate analyses were performed to estimate latency time by anatomical site, gender, diagnostic period and industry sector.

Results: Mesothelioma incidence rates among men were higher than among women during the overall period. The incidence of pleural mesothelioma in men leveled off until 2009 (6.50 per 100,000) with a slight decrease thereafter. For women, the rate increased until 2006 (1.31 per 100,000) and then remained relatively stable. The incidence of peritoneal mesothelioma in men was constant whereas rate among women increased during 2010-2015. The number of cases diagnosed during three-year periods remained level. In multivariate model, site and gender were not relevant for latency period whereas construction workers had a shorter latency than shipyard workers.

Conclusions: Despite the asbestos ban since 1992, occupational exposure is still at risk. This highlights the need to assess exposure levels and to find a reliable health surveillance tool.
Asymptomatic localized pleural amyloidosis mimicking malignant pleural mesothelioma: report of a case. T. Nakano, S. Endo, K. Tetsuka, et al. 2016;8(1):E157-60. Case report PubMed · Publisher · Free full text

Abstract

We herein report an asymptomatic 65-year-old male with localized pleural amyloidosis mimicking malignant pleural mesothelioma. He had a history of exposure to asbestos and was admitted for investigation of an abnormal pleural thickness detected by chest radiography. Positron emission tomography showed elevation of standardized uptake value corresponding to the pleural thickness. Partial pleurectomy including the tumor was performed for the purpose of diagnosis and local disease control. The pathological examination showed that the tumor was pleural amyloidosis. The tumor was diagnosed as localized primary amyloidosis, because serum monoclonal protein concentration did not increase. Pleural amyloidosis should be considered as a differential diagnosis from pleural mesothelioma.
Flex-rigid pleuroscopic biopsy with the SB knife Jr is a novel technique for diagnosis of malignant or benign fibrothorax. X.B. Wang, Y. Yin, Y. Miao, et al. 2016;8(11):E1555-E1559. Case report PubMed · Publisher · Free full text

Abstract

Diagnosing pleural effusion is challenging, especially in patients with malignant or benign fibrothorax, which is difficult to sample using standard flexible forceps (SFF) via flex-rigid pleuroscopy. An adequate sample is crucial for the differential diagnosis of malignant fibrothorax (malignant pleural mesothelioma, metastatic lung carcinoma, etc.) from benign fibrothorax (benign asbestos pleural disease, tuberculous pleuritis, etc.). Novel biopsy techniques are required in flex-rigid pleuroscopy to improve the sample size and quality. The SB knife Jr, which is a scissor forceps that uses a mono-pole high frequency, was developed to allow convenient and accurate resection of larger lesions during endoscopic dissection (ESD). Herein, we report two patients with fibrothorax who underwent a pleural biopsy using an SB knife Jr to investigate the potential use of this tool in flex-rigid pleuroscopy when pleural lesions are difficult to biopsy via SFF. The biopsies were successful, with sufficient size and quality for definitive diagnosis. We also successfully performed adhesiolysis with the SB knife Jr in one case, and adequate biopsies were conducted. No complications were observed. Electrosurgical biopsy with the SB knife Jr during flex-rigid pleuroscopy allowed us to obtain adequate samples for the diagnosis of malignant versus benign fibrothorax, which is usually not possible with SFF. The SB knife Jr also demonstrated a potential use for pleuropulmonary adhesions.
Localized malignant pleural sarcomatoid mesothelioma misdiagnosed as benign localized fibrous tumor. K.C. Kim, H.P. Vo. 2016;8(6):E379-84. Case report PubMed · Publisher · Free full text

Abstract

Localized malignant pleural mesothelioma (LMPM) is a rare tumor with good prognosis by surgical resection. We report an atypical case of malignant pleural sarcomatoid mesothelioma (SM) in an asymptomatic 65-year-old woman, who had no history of exposure to asbestos. She presented with a small pleural mass without pleural effusion and was misdiagnosed as a benign localized fibrous tumor (BLFT) on pathologic examination through a surgical tumor specimen. However, seven months later, the patient returned with serious cancerous symptoms. A large recurrent tumor mass was found within the chest wall invading at the old surgical resection site. SM, a subtype of LMPM, was confirmed with histopathogy and immunohistochemisty. In conclusion, malignant pleural mesothelioma (MPM) can present with typical radiologic finding similar to a BLFT, and has a wide histopathologic presentation in biopsy specimen. A thorough pathologic investigation should be attempted even when a pleural mass resembles benign, localized, and small on radiologic studies.
Relationships between chronic obstructive pulmonary disease and lung cancer: biological insights. E. Barreiro, V. Bustamante, V. Curull, et al. 2016;8(10):E1122-E1135. Review PubMed · Publisher · Free full text

Abstract

Lung cancer (LC) has become one of the leading causes of preventable death in the last few decades. Cigarette smoking (CS) stays as the main etiologic factor of LC despite that many other causes such as occupational exposures, air pollution, asbestos, or radiation have also been implicated. Patients with chronic obstructive pulmonary disease (COPD), which also represents a major cause of morbidity and mortality in developed countries, exhibit a significantly greater risk of LC. The study of the underlying biological mechanisms that may predispose patients with chronic respiratory diseases to a higher incidence of LC has also gained much attention in the last few years. The present review has been divided into three major sections in which different aspects have been addressed: (I) relevant etiologic agents of LC; (II) studies confirming the hypothesis that COPD patients are exposed to a greater risk of developing LC; and (III) evidence on the most relevant underlying biological mechanisms that support the links between COPD and LC. Several carcinogenic agents have been described in the last decades but CS remains to be the leading etiologic agent in most geographical regions in which the incidence of LC is very high. Growing evidence has put the line forward the implications of COPD and especially of emphysema in LC development. Hence, COPD represents a major risk factor of LC in patients. Different avenues of research have demonstrated the presence of relevant biological mechanisms that may predispose COPD patients to develop LC. Importantly, the so far identified biological mechanisms offer targets for the design of specific therapeutic strategies that will further the current treatment options for patients with LC. Prospective screening studies, in which patients with COPD should be followed up for several years will help identify biomarkers that may predict the risk of LC among these patients.
Validation of EORTC and CALGB prognostic models in surgical patients submitted to diagnostic, palliative or curative surgery for malignant pleural mesothelioma. A. Sandri, F. Guerrera, M. Roffinella, et al. 2016;8(8):2121-7. PubMed · Publisher · Free full text

Abstract

Background: To assess the trend of our surgical patients affected by malignant pleural mesothelioma (MPM) and submitted to diagnostic/palliative or curative surgical procedures and to validate the European Organisation for Research and Treatment of Cancer (EORTC) prognostic score in our patient population.

Methods: This is a cohort study of patients submitted to surgery for MPM from January 2007 to December 2013. Primary outcome was overall survival (OS). Univariate and multivariate-adjusted comparisons by EORTC prognostic score for OS were accomplished using Cox method. Adjusted models included the following clinical variables: kind of procedure, smoking habit, asbestos exposure, Charlson's Comorbidity Index (CCI), clinical tumor stage, adjuvant chemotherapy, dyspnoea, chest pain and haematological variables according to the score features. Nomenclature of the surgical procedures matches the International Association for the Study Lung Cancer (IASLC)/International Mesothelioma Interest Group (iMIG).

Results: One-hundred sixty-six consecutive cases were collected: the median age at surgery was 73 years and 123 patients (75%) had a history of asbestos exposure. Ninty patients (54%) were submitted to a palliative/diagnostic thoracoscopy, 30 to pleurectomy/decortication (P/D), and 6 to extra-pleural pneumonectomy (EPP). Clinical TNM stages were as follows: 99 (60%) stage I-II, 34 (20%) stage III and 33 (20%) stage IV. The median follow-up (FU) was 19 months [interquartile range (IQR), 9-31 months] and the FU-completeness was 98%. By the end of the study 130 patients died (78%). One- and 3-year OS was 60% and 36%, respectively. Patients submitted to EPP and P/D showed a better survival (P=0.013). Multivariable model showed an independent prognostic value of EORTC score (HR =2.86, P<0.001).

Conclusions: In selected patients, aggressive surgical approaches, although not radical, may still be beneficial. The EORTC prognostic index proved to be an independent prognostic factor in our cohort of patients and therefore is a reliable and valid instrument that may be implemented in the daily practice.
MicroRNAs in mesothelioma: from tumour suppressors and biomarkers to therapeutic targets. G. Reid. 2015;7(6):1031-40. Review PubMed · Publisher · Free full text

Abstract

Malignant mesothelioma remains a difficult proposition in the clinic, with few accurate molecular markers available to guide diagnosis and patient management, and a dearth of effective treatments. Recent evidence implicates microRNAs-short non-coding RNAs involved in post-transcriptional regulation of gene expression-in mesothelioma biology. Emerging evidence suggests that exploring aberrant microRNA expression will not only improve our understanding of the disease, but will also lead to the identification of new molecular biomarkers and therapeutic targets.
Pleural mesothelial cells in pleural and lung diseases. H. Batra, V.B. Antony. 2015;7(6):964-80. Review PubMed · Publisher · Free full text

Abstract

During development, the mesoderm maintains a complex relationship with the developing endoderm giving rise to the mature lung. Pleural mesothelial cells (PMCs) derived from the mesoderm play a key role during the development of the lung. The pleural mesothelium differentiates to give rise to the endothelium and smooth muscle cells via epithelial-to-mesenchymal transition (EMT). An aberrant recapitulation of such developmental pathways can play an important role in the pathogenesis of disease processes such as idiopathic pulmonary fibrosis (IPF). The PMC is the central component of the immune responses of the pleura. When exposed to noxious stimuli, it demonstrates innate immune responses such as Toll-like receptor (TLR) recognition of pathogen associated molecular patterns as well as causes the release of several cytokines to activate adaptive immune responses. Development of pleural effusions occurs due to an imbalance in the dynamic interaction between junctional proteins, n-cadherin and β-catenin, and phosphorylation of adherens junctions between PMCs, which is caused in part by vascular endothelial growth factor (VEGF) released by PMCs. PMCs play an important role in defense mechanisms against bacterial and mycobacterial pleural infections, and in pathogenesis of malignant pleural effusion, asbestos related pleural disease and malignant pleural mesothelioma. PMCs also play a key role in the resolution of inflammation, which can occur with or without fibrosis. Fibrosis occurs as a result of disordered fibrin turnover and due to the effects of cytokines such as transforming growth factor-β, platelet-derived growth factor (PDGF), and basic fibroblast growth factor; which are released by PMCs. Recent studies have demonstrated a role for PMCs in the pathogenesis of IPF suggesting their potential as a cellular biomarker of disease activity and as a possible therapeutic target. Pleural-based therapies targeting PMCs for treatment of IPF and other lung diseases need further exploration.
Preoperative evaluation for lung cancer resection. D. Spyratos, P. Zarogoulidis, K. Porpodis, et al. 2014;6 Suppl 1(Suppl 1):S162-6. Review PubMed · Publisher · Free full text

Abstract

During the last decades lung cancer is the leading cause of death worldwide for both sexes. Even though cigarette smoking has been proved to be the main causative factor, many other agents (e.g., occupational exposure to asbestos or heavy metals, indoor exposure to radon gas radiation, particulate air pollution) have been associated with its development. Recently screening programs proved to reduce mortality among heavy-smokers although establishment of such strategies in everyday clinical practice is much more difficult and unknown if it is cost effective compared to other neoplasms (e.g., breast or prostate cancer). Adding severe comorbidities (coronary heart disease, COPD) to the above reasons as cigarette smoking is a common causative factor, we could explain the low surgical resection rates (approximately 20-30%) for lung cancer patients. Three clinical guidelines reports of different associations have been published (American College of Chest Physisians, British Thoracic Society and European Respiratory Society/European Society of Thoracic Surgery) providing detailed algorithms for preoperative assessment. In the current mini review, we will comment on the preoperative evaluation of lung cancer patients.
Bronchoalveolar neutrophilia inversely correlates with DLCO at diagnosis in asbestosis but not lung function decline at 1 year. G. Walters, S. Agarwal, K. Singh, et al. 2013;5(3):314-6. PubMed · Publisher · Free full text

Abstract

The role of bronchoalveolar lavage (BAL) in the assessment of interstitial lung disease (ILD) remains controversial. Previous studies have demonstrated that BAL cell differential is useful in predicting disease progression in many forms of ILD. We wished to investigate whether BAL had a similar use in predicting disease progression in asbestosis. 21 patients who had significant asbestos exposure, findings of UIP radiologically and BAL performed as part of their investigation were reviewed. There was a significant inverse correlation between percentage BAL neutrophils and percentage predicted DLCO at diagnosis (n=21; P=0.02; r(2)=(-)0.25; CI, (-)0.77(-)0.08), but not with DLCO decline over 1 year. Unlike previous reports in IPF, BAL cell differential is not predictive of decline in classic asbestosis with a UIP pattern and its routine use in this cohort of patients provides little if any additional benefit.
Clinical practice guidelines for malignant pleural mesothelioma. N. van Zandwijk. 2013;5(6):724-5. PubMed · Publisher · Free full text

Summary

This editorial introduced clinical practice guidelines for malignant pleural mesothelioma published in the Journal of Thoracic Disease. The author, of the Asbestos Diseases Research Institute in Concord, Australia, described malignant pleural mesothelioma as the most common type of mesothelioma and a nearly invariably lethal tumour of the pleura. He noted that it was very seldom diagnosed before widespread asbestos mining in the early to mid twentieth century and had risen sharply in incidence over the last five decades. Worldwide asbestos consumption peaked in the 1980s, but the author stated that its use appeared to be gaining unprecedented popularity in Eastern Europe, Asia and South America, so that many more cases would be diagnosed in the future. He also noted the long latency between first exposure and disease, difficult diagnosis, underreporting especially in developing countries, distressing symptoms, difficult treatment and frequent therapeutic nihilism among health professionals. He stated that guidelines published in the previous ten years had not used the structured systematic review approach required by the Australian National Health and Medical Research Council. The new guidelines were based on a systematic review of the literature, with every relevant publication reviewed and scored by at least three independent medical specialists. They gave concise evidence-based recommendations for diagnosis, treatment and care. They were written for an Australian context, but the author stated they could be translated to other health care settings.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.
Malignant pleural effusion and algorithm management. K. Zarogoulidis, P. Zarogoulidis, K. Darwiche, et al. 2013;5 Suppl 4(Suppl 4):S413-9. Review PubMed · Publisher · Free full text

Abstract

Involvement of the pleura in lung cancer is a common manifestation accompanying with reduced life expectancy. Symptoms relief and improvement of the quality of life are the primary goals of the management of malignant pleural effusion (MPE). Histological confirmation is essential for optimal patient management. Lung cancer patients, with life expectancy more than 3 months, resistant to chemotherapy should be treated with thoracentesis, intercoastal tube drainage and installation of a sclerosant agent or pleurodesis through thoracospopic procedures or placement of an indwelling pleura catheter. Talc pleurodesis (sterile asbestos-free graded, particle size >15 μm), as "poudrage" or "slurry" still remains the treatment of choice in patients with MPE resistant to chemotherapy.

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