bims-mesote 2023-08-20 papers

Issue of 2023–08–20
four papers selected by
Laura Mannarino, Humanitas Research

Transl Lung Cancer Res. 2023 Jul 31. 12(7): 1384-1390

Does hyperthermic povidone-iodine lavage increase the apoptotic rate of residual cancer cell in patients with malignant pleural mesothelioma?-a prospective pilot study.

Andrea Bille, Hiral Jhala, Leanne Ashrafian, Leanne Allison, Matthew Russell, Roland Fleck, Daisuke Nonaka.

Background: Malignant pleural mesothelioma (MPM) is an incurable, late presenting primary cancer, conferring a survival of 8-14 months. Different intrapleural treatments have been tested as part of a multimodality approach to treat a select group of patients with limited disease, increasing survival. Recently, povidone-iodine has been shown to induce apoptosis in microscopic tumour cells in vitro, with no reported complications. This is the first in vivo study assessing the apoptotic rate caused by intraoperative hyperthermic betadine lavage using routine immunohistochemistry combined with transmission electron microscopy (TEM).
Methods: We included surgically fit patients aged >18, undergoing minimally invasive video-assisted thoracoscopic surgery (VATS) pleural biopsy between December 2016 and February 2018, for confirmed or presumed pleural malignancy. Parietal pleural biopsies were obtained at 7.5, 15 and 30 minutes after hyperthermic betadine lavage, and compared to pre-lavage biopsy samples, for apoptotic changes. Viable tumour samples underwent histological, immunohistochemical and ultrastructural analysis as well as TEM for features of apoptosis.
Results: N=6. Median age was 76 years. Median overall survival was 26.7 months. There was no statistical impact on survival of side of disease (left vs. right). There was no significant difference in expressions of markers of apoptotic index pre and post betadine treatment upon immunohistochemical analysis. There was no discernible effect on morphological features of apoptosis seen with betadine treatment, on TEM analysis. No side effects were identified post betadine lavage.
Conclusions: Although hyperthermic betadine lavage is a safe antiseptic solution with no toxicity when performed intraoperatively, it confers no effect on apoptotic rate or necrosis. It is therefore unlikely that hyperthermic betadine lavage will have an impact on reducing the microscopic residual disease after pleurectomy decortication and enhancing survival.

Keywords: Malignant pleural mesothelioma (MPM); apoptosis; betadine lavage; transmission electron microscopy (TEM)

DOI: https://doi.org/10.21037/tlcr-22-282

Diagn Cytopathol. 2023 Aug 15.

Malignant mesothelioma cells with characteristic intracytoplasmic vacuolization and lipids.

Satoshi Morito, Hiroshi Yasui, Tomoo Itoh, Shingo Kamoshida, Hiroyuki Ohsaki.

In this brief report, we described some uncommon cytomorphological features of malignant mesothelioma (MM) cells in pleural effusions. The tumor cells exhibited abundant cytoplasmic vacuolization, with presence of single or multiple eccentric nuclei in several cells. In the Giemsa-stained smear, we observed a glossy spherical material in some cells, which tested positive in Sudan III stain. In immunocytochemical analysis, tumor cells were positive for calretinin, podoplanin, epithelial membrane antigen, and methylthioadenosine phosphorylase; tumor cells were negative for BRCA1-associated protein 1, CD68, and desmin. The intracytoplasmic vacuoles were positive for adipophilin expression.

Keywords: cytology; foamy cells; lipids; malignant mesothelioma; pleural effusion

DOI: https://doi.org/10.1002/dc.25213

Thorac Cancer. 2023 Aug 13.

Strategies to reduce morbidity following pleurectomy and decortication for malignant pleural mesothelioma.

Patrick Bou-Samra, Austin Chang, Kevin Zhang, Feredun Azari, Gregory Kennedy, Emily Guo, Wei-Ting Hwang, Sunil Singhal.

BACKGROUND: Pleurectomy and decortication (PD) in malignant pleural mesothelioma has a high morbidity mostly associated with aspiration pneumonia (PNA), deep vein thrombosis (DVT), and foreign catheter sepsis. We instituted four strategies to reduce these complications and report our experience.
METHODS: This was a retrospective review of patients who underwent PD at the University of Pennsylvania between 2015 and 2022. Our patients underwent standard of care PD in addition to tracheostomy and gastrostomy/jejunostomy tube with therapeutic anticoagulation (AC) leading up to surgery. Measured outcomes were postoperative PNA, DVT, and sepsis. The predicted risk of those same outcomes had patients not undergone the interventions was calculated based on the American College of Surgeons (ACS) surgical risk calculator (SRC). A McNemar's test was used to determine whether the risk of having PNA, DVT and sepsis differed between the two subgroups.
RESULTS: Fifty-five patients were included in the study. The mean age was 70 years (SD 6.2) with a mean of 21 (SD 19) pack-years of smoking. PNA, DVT, and catheter-related sepsis occurred in 12, four, and seven patients, respectively. Upon using the ACS SRC prediction model of the nonintervention group, PNA, DVT and catheter related sepsis was predicted to occur in 24 (paired data OR 5, 95% CI: 1.4-17.2; McNemar's test p = 0.008), 14 (paired data OR 3.5, 95% CI: 1.15-10.6; McNemar's test p = 0.03), and 17 (paired OR 3, 95% CI: 1.09-8.3; McNemar's test p = 0.04) patients, respectively.
DISCUSSION: Patients undergoing tracheostomy creation, therapeutic AC at the time of diagnosis, and gastrostomy tube placement had a reduced risk of aspiration PNA, DVT, and catheter sepsis.

Keywords: morbidity; pleural mesothelioma; pleurectomy and decortication

DOI: https://doi.org/10.1111/1759-7714.15067

Pharmacoeconomics. 2023 Aug 12.

Cost Effectiveness and Budget Impact of Nivolumab Plus Ipilimumab Versus Platinum Plus Pemetrexed (with and Without Bevacizumab) in Patients with Unresectable Malignant Pleural Mesothelioma in Switzerland.

Michaela Carla Barbier, Alicia Fengler, Esther Pardo, Arjun Bhadhuri, Niklaus Meier, Oliver Gautschi.

BACKGROUND: Malignant pleural mesotheliomas (MPMs) are aggressive and often unresectable. In the past, chemotherapy was the standard for palliative treatment. However, immunotherapy with nivolumab+ipilimumab has recently received marketing approval.
OBJECTIVES: This study evaluated the cost effectiveness of nivolumab+ipilimumab versus pemetrexed+platinum (with/without bevacizumab) for Swiss patients with unresectable MPM, overall and by histological subtype.
METHODS: We developed a three-state Markov cohort model with a cycle length of 1 month, a 30-year time horizon, and a discount rate of 3% per year for costs and benefits. The model included the updated survival and treatment-dependent utility results from the Checkmate-743 and MAPS registration trials. A Swiss statutory health insurance perspective was considered with unit costs for 2022 from publicly available and real-world sources. We assumed a willingness-to-pay (WTP) threshold of CHF100,000/QALY. Model robustness was explored in sensitivity and scenario analyses.
RESULTS: Compared with chemotherapy, nivolumab+ipilimumab incurred additional costs of CHF109,115 and 0.57 additional quality-adjusted life-years (QALYs), yielding an incremental cost-effectiveness ratio (ICER) of CHF192,585/QALY (i.e. USD201,829/QALY) gained. Relative to their 2022 list price, nivolumab+ipilimumab may be cost effective if priced at 48% across all histologies. Assuming cisplatin-based instead of carboplatin-based chemotherapy reduced the ICER to CHF158,911/QALY (i.e. USD166,539/QALY). For the non-epithelioid subtype, nivolumab+ipilimumab was cost effective compared with chemotherapy (ICER of CHF97,894/QALY, i.e. USD102,593/QALY). Chemotherapy+bevacizumab was often a dominated strategy or would require a bevacizumab cost reduction to 28%.
CONCLUSIONS: Our model projected nivolumab+ipilimumab to be cost effective for the non-epithelioid subtype but not for all histologies. Substantial discounts for nivolumab+ipilimumab would be necessary to achieve cost effectiveness for all histologies.

DOI: https://doi.org/10.1007/s40273-023-01305-3