bims-mesote 2026-05-31 papers

Issue of 2026–05–31
four papers selected by
Laura Mannarino, Humanitas Research

J Thorac Dis. 2026 Apr 30. 18(4): 309

Impact of intercostal nerve cryoablation on opioid use in pleural mesothelioma surgery: results from a high-volume integrated regional center.

Alison S Baskin, Seif Elmankabadi, Vincent Zhang, Pranita Mishra, Kian C Banks, Julia Wei, Jeffrey B Velotta.

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.

Keywords: Pleural mesothelioma (PM); cryoablation; intercostal nerve; pain management; pleurectomy and decortication

DOI: https://doi.org/10.21037/jtd-2026-1-0076

Medicina (Kaunas). 2026 Apr 29. pii: 845. [Epub ahead of print]62(5):

Comorbidity Burden in Lung Cancer and Malignant Pleural Mesothelioma: Nationwide Database Results of Turkey.

Çiğdem Özdilekcan, Tarkan Özdemir, Mustafa Hamidullah Türkkanı, Naim Ata, Mesut Akyol, Mevlüt Karataş, Aslıhan Gürün Kaya, Aydın Yılmaz, Akın Kaya, Şuayip Birinci.

Background and Objectives: The presence of comorbidities in both the pre- and post-diagnostic periods is a critical consideration in the diagnosis and management of patients with cancer. This study aimed to investigate the prevalence and burden of pulmonary and extrapulmonary comorbidities in patients diagnosed with lung cancer (LC) and malignant pleural mesothelioma (MPM). Materials and Methods: The data were obtained from official patient records of the Turkish Ministry of Health. Patients diagnosed with either lung cancer (LC) or malignant pleural mesothelioma (MPM) between 2015 and 2018 were included in the study. Comorbidities were classified as pulmonary or extrapulmonary. Results: A total of 74,835 patients with LC and 1678 patients with MPM were included. The burden of comorbid conditions increased significantly in the post-diagnostic period in both males and females across both cancer types. When the two cancer groups were compared with respect to diagnostic periods, comorbidities such as hypertension (HT), phlebitis/venous thrombosis/thrombophlebitis, pulmonary embolism, pneumothorax, and pleural effusion were significantly more prevalent in the MPM group (p < 0.05). Compared with the pre-diagnostic period, the comorbidity risk in LC was highest for pulmonary embolism, ARF, and pneumonia in the post-diagnostic period, whereas renal failure was the most frequent comorbidity in the MPM group (p < 0.001 and p = 0.024). When comparing changes in comorbidity burden between sexes in the lung cancer group, male patients had higher frequencies of pulmonary embolism, pneumonia, pneumothorax, and coronary artery disease than females. In contrast, in the female lung cancer group, the prevalence of chronic renal failure was higher than in males (OR = 2.14 vs. 2.00), whereas acute renal failure was more prominent in the male patient group (OR = 2.64 vs. 1.94). In gender-based comparison of comorbid conditions among patients with MPM, the risk of renal failure was higher in females than in males (CRF and ARF respectively: OR = 2.63 vs. 2.16 and OR = 6.80 vs. 5.44). Additionally, increased rates of COPD were observed in male patients within this group (OR = 1.93 vs. 1.81). Conclusions: Patients with LC and MPM are burdened not only by their primary malignancies but also by a wide spectrum of comorbidities, particularly in the post-diagnostic period. Comprehensive knowledge of comorbid conditions is essential for clinicians to guide clinical decision-making, anticipate disease progression, and optimize treatment strategies, thereby informing national healthcare policies. Future studies incorporating matched control groups or longitudinal designs with standardized surveillance protocols may help conduct better research.

Keywords: comorbidity; lung cancer; malignant pleural mesothelioma

DOI: https://doi.org/10.3390/medicina62050845

Ann Thorac Surg. 2026 May 28. pii: S0003-4975(26)00482-0. [Epub ahead of print]

Feasibility and Outcomes of Cytoreductive Surgery and Hyperthermic Intrathoracic Chemoperfusion for Pleural Mesothelioma.

Yota Suzuki, Inderpal S Sarkaria, Edra Ha, Ian G Christie, Olugbenga Okusanya, Omar Awais, Evan T Alicuben, Ryan M Levy, James D Luketich, Neil A Christie.

BACKGROUND: The management of pleural mesothelioma requires a multidisciplinary approach, and hyperthermic intrathoracic chemoperfusion (HITHOC) following surgical cytoreduction may improve local disease control. However, with the release of the Mesothelioma and Radical Surgery 2 (MARS 2) trial results, the role of surgical intervention has been questioned due to its high perioperative mortality.
METHODS: We conducted a single-institution retrospective study on patients who underwent cytoreductive surgery (extrapleural pneumonectomy [EPP] or pleurectomy and decortication [PD]) and intraoperative HITHOC for pleural mesothelioma between January 2009 and December 2023.
RESULTS: During the study period, 69 patients underwent cytoreductive surgery with HITHOC (55 PD, 14 EPP). The median age was 67 years, and 73.9% were male. Major complications (Clavien-Dindo ≥III) occurred in 12.7% of the PD cohort and 50.0% of the EPP cohort. No clinically significant AKI (Stage ≥2) occurred in the PD cohort, whereas it occurred in two patients in the EPP cohort (14.3%). There was no 90-day mortality in the PD cohort (0%), whereas two (14.3%) were observed in the EPP cohort. In the PD cohort, adjuvant chemotherapy was administered to 33 patients (60%), which was associated with significantly longer overall survival (median: 55.0 vs 18.2 months; p < 0.001).
CONCLUSIONS: HITHOC with PD was a feasible treatment modality, yielding excellent short-term outcomes that compare favorably with contemporary multicenter data, including MARS 2. With careful patient selection and optimization of perioperative care, HITHOC with PD may have a role for local control in pleural mesothelioma even in the post-MARS 2 era.

DOI: https://doi.org/10.1016/j.athoracsur.2026.05.017

Med. 2026 May 28. pii: S2666-6340(26)00152-2. [Epub ahead of print] 101149

Loss of tumor suppressor NF2 mediates resistance to CAR T cell and anti-PD-1 therapy: Strategies to restore immunotherapy sensitivity.

Miguel A Lopez-Lago, Meriem Taleb, Mehek Ningoo, Tomoyo Okada, Xiaoyu Li, Hyun-Sung Lee, Bryan M Burt, Michael Offin, Navin K Chintala, Prasad S Adusumilli.

BACKGROUND: Investigating the biological mechanisms of acquired resistance to immunotherapy remains a necessity for effective treatment of solid tumors.
METHODS: Diffuse pleural mesothelioma (DPM) tumors, from immunocompetent and immunodeficient mouse models with acquired resistance to chimeric antigen receptor (CAR) T cell therapy were analyzed using flow cytometry, immunofluorescence, and ELISA. The interplay between genetic alterations in the cancer cell and site-specific tumor immune microenvironment (TIME) was characterized; therapies to reverse immunotherapy resistance were investigated.
FINDINGS: Analysis of tumors with acquired resistance to CAR T cell therapy demonstrated lower expression of tumor suppressor NF2. Enforced depletion of NF2 promoted resistance to CAR T cell and anti-PD-1 therapy in DPM but not in heterotopic subcutaneous tumors. Loss of NF2 was associated with accumulation of immunosuppressive complement receptor of immunoglobulin superfamily (CRIg)+ macrophages in pleural tumors, which was dependent on tumor-secreted chemokines and retinoic acid. Ablation of chemokines or pharmacologic inhibition of retinoic acid or the Hippo pathway by use of TEAD inhibitors restored sensitivity to CAR T cell therapy. Correspondingly, in two independent cohorts of patients, DPM tumors with NF2 copy-number loss, but not mutations, were associated with higher infiltration of M2 macrophages, lower infiltration and function of CD8 T cells, and an anti-PD-1-resistant gene signature.
CONCLUSIONS: Our study uncovers a previously unknown mechanism of resistance to immunotherapy by identifying the dynamic interplay between cancer cell genetic alterations and the TIME.
FUNDING: This research was funded in part through the NCI UG3CA290241, R01CA292664, R01CA235667, R01CA236615, and Department of War CA200437.

Keywords: CAR therapy; Hippo pathway; PD-1 blockade; Pre-clinical research; TEAD inhibitors; acquired resistance; checkpoint blockade therapy; immunosupression; immunotherapy; tumor suppressor; tumor-associated macrophages

DOI: https://doi.org/10.1016/j.medj.2026.101149