OBJECTIVES For centrally located lung tumours, sleeve lobectomy is preferred over pneumectomy. We report on surgical practices and peri-operative outcomes of sleeve resections based on the European Society of Thoracic Surgeons database. METHODS We retrieved data of patients undergoing sleeve lobectomy or bilobectomy from 2007 to 2021. We evaluated baseline characteristics, surgical approach, neo-adjuvant treatments, morbidity and post-operative outcomes of open and video-assisted thoracic surgery (VATS) procedures. RESULTS In total, 1652 patients (median age: 63; f/m: 446/1206) underwent sleeve lobectomy (n = 1536) or bilobectomy (n = 116) by open thoracotomy (n = 1491; 90.2%) or VATS (n = 161; 9.8%) with thoracotomy conversion rate of 21.1% (n = 34). 398 (24.1%) received neo-adjuvant treatment. Overall morbidity and 30-day mortality were 40.6% and 2.2% respectively. Bronchial anastomotic complications occurred in 29 patients (1.8%) with conservative treatment in 6 cases (20.7%) and operative management in 23 (79.3%). On multivariable analysis, factors of elevated risk of cardiopulmonary complications were BMI < 20 (OR: 2.26; P < 0.001) and bilobectomy (OR : 2.28, p < 0.001). Age <60 (OR. 0.71, p = 0.013), female sex (OR: 0.54, p < 0.001) and VATS (0.64, p < 0.001) were associated with decreased risk. Neo-adjuvant treatment was not associated with increased risks of cardiopulmonary complications (OR: 1.05; p = 0.664). Compared to open thoracotomy, VATS was associated with significantly decreased overall morbidity (30.4% vs 41.7%, p = 0.006) and length of stay (median: 5 days vs 8 days; p < 0.001). CONCLUSION Sleeve lobectomies can be safely performed after neo-adjuvant treatment. VATS approach fosters shorter length of stay and decreased morbidity.

OBJECTIVES Between 10% and 40% of patients who receive a left ventricular assistance device (LVAD) suffer from right ventricular failure (RVF) shortly after the device is implanted. Patients with post-LVAD RVF tend to have poor outcomes. Only a few predictive factors concerning the right ventricle (RV) have been investigated. Our goal was to search for non-invasive variables that correlate with RV function, focusing on echocardiographic parameters of the RV. METHODS We selected 3 parameters: tricuspid annular plane systolic excursion, right ventricular fractional area change and right ventricular global longitudinal strain. We searched the literature and pooled relevant studies in a meta-analysis. Finally, we performed a statistical analysis to confirm whether each parameter was a reliable predictor of RVF after LVAD implantation. RESULTS We retained 19 articles involving a total of 1561 patients. We found a pooled standardized mean deviation of −0.13 cm for the tricuspid annular plane systolic excursion, with the lower and upper tails of −0.21 and −0.04 cm, respectively. Concerning the right ventricular fractional area change, the averaged standardized mean deviation was equal to −2.61%, with the lower and upper extremities of −4.12% and −1.09%, respectively. Finally, regarding the global longitudinal strain, the standardized mean deviation was equal to −2.06% with an uncertainty value between −3.23% and −0.88%. CONCLUSIONS The tricuspid annular plane systolic excursion could be a reliable parameter in RVF prediction. The right ventricular fractional area change and global longitudinal strain are likely to be stronger predictors of RVF after LVAD implantation. Prospective studies should be carried out to confirm this observation.

Background: Sleeve lobectomy (SL) is a lung-sparing procedure, which is accepted as a valid operation for centrally-located advanced tumors. These tumors often require induction treatment by chemotherapy and/ or radiotherapy to downstage the disease and thus facilitate subsequent surgery. However, induction therapy may potentially increase the risk of bronchial anastomotic complications and related morbidity. This metaanalysis aims to determine the impact of induction therapy on the outcomes of pulmonary SL. Methods: We compared studies of patients undergoing SL or bilobectomy for non-small cell lung cancer (NSCLC) with and without induction therapy. Outcomes of interest were in-hospital mortality, morbidity, anastomosis complication and 5-year survival. Odds ratio (OR) were computed following the Mantel-Haenszel method. Results: Ten studies were included for a total of 1,204 patients. There was no statistical difference for between patients who underwent induction therapy followed by surgery and patients who underwent surgery alone in term of post-operative mortality (OR: 1.80, 95% confidence interval (CI): 0.76-4.25, P value =0.19) and morbidity (OR: 1.17, 95% CI: 0.90-1.52, P value =0.237). Anastomosis related complications rate were 5.2% and appears increased after induction therapy with a statistical difference close to the significance (OR:1.65, 95% CI: 0.97-2.83, P value =0.06). Patients undergoing surgery alone showed better survival at 5 years (OR: 1.52, 95% CI: 1.15-2.00, P value =0.003).Conclusions: SL following induction therapy can be safely performed with no increase of mortality and morbidity. However, the need for induction therapy before surgery is associated with increased anastomotic complications and poorer survival prognosis at 5 years.

Introduction: The management of malignant pleural mesothelioma (MPM) remains challenging with poor patient survival. Local therapies such as hyperthermic intrathoracic cisplatin (HITOC) have shown good tumor control in selected patients. HITOC was shown to increase MPM drug exposure while limiting systemic side effects but alternative mechanisms for HITOC are still lacking. Here, we hypothesized that HITOC induces an immune response directed against MPM which decreases cancer related mortality. Methods: We implanted AB12-luc MPM cells in the pleural cavity of BALB/c mice. A chemotherapy perfusion circuit was downsized to administer cisplatin (80mg/m2 equivalent dose) in the thoracic cavity at normo (37°C, ITOC) or hyperthermic (39°C, HITOC) conditions for 30 minutes. Tumor growth (visualized by bioluminescence) and mouse survival were then assessed. We determined tumor platinum content and distribution by inductively coupled plasma mass spectrometry (ICP-MS) and by laser ablation ICP-MS (LA-ICP-MS) respectively. We also questioned the impact of (H)ITOC on the MPM immune microenvironment (innate and adaptive immune cells, activity and checkpoint expression) by 16-colour flow cytometry and immunohistochemistry. Finally, tumor response to (H)ITOC was assessed in BALB/c athymic mice implanted with AB12-luc cells. Results: MPM tumor control and mouse survival were significantly improved by HITOC compared to controls (ITOC, saline 37 and 39°C). Tumor platinum content was significantly higher in HITOC compared to ITOC but was majorly located at the surface of tumors. HITOC enhanced MPM infiltration by CD8+Granzyme B+ T-cells and decreased the levels of MCHII−/CD80− (M2-like) macrophages compared to controls at day 7. Interestingly, immune checkpoint expression of PD1 and CTLA4 was significantly enhanced in CD8+ lymphocytes in HITOC treated MPM compared to controls at day 7. Finally, the lack of T lymphocytes (BALB/c athymic mice) abrogated the impact of HITOC on MPM control and mouse survival. Conclusion: HITOC improves MPM control through a T lymphocyte immune mediated response. The enhanced immune checkpoint (PD1/CTLA4) expression in CD8+ lymphocytes opens perspectives for the combination of HITOC with immune checkpoint inhibitors. Citation Format: Yameng Hao, Aspasia Gkasti, Louis-Emmanuel Chriqui, Damien Marie, Michel Gonzalez, Thorsten Krueger, Solange Peters, Paul J. Dyson, Etienne Meylan, Johanna Joyce, Sabrina Cavin, Jean Y. Perentes. Hyperthermic intrathoracic chemotherapy (HITOC) improves malignant pleural mesothelioma control through a tumor specific cytotoxic immune response. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6399.

Introduction: Malignant pleural mesothelioma (MPM) is an aggressive cancer with limited treatment options. The application of photodynamic therapy (PDT) was shown to significantly improve patient survival. Previously, we found that low dose PDT (L-PDT) enhanced the immune infiltration of MPM and increased the impact of immune checkpoint inhibitors on tumor control. However, the mechanisms behind these observations are unknown. Here, in an orthotopic murine model of MPM, we show that L-PDT upregulates tumor vascular E-Selectin expression via NF-kB. This upregulation favors enhanced leukocyte trafficking and immune mediated MPM regression. Methods: We analyzed adhesion molecules (E-Selectin, ICAM-1, VCAM-1) and canonical NF-kB activation (phosphorylated IκBα) protein levels in endothelial (ECRF-24) cells treated by L-PDT in the presence or absence of a NEMO/IKKγ siRNA in vitro. For in vivo validation, AB12-Luc MPM cells were grown in the pleural cavity of syngeneic BALB/c mice and treated with L-PDT (verteporfin 400 µg/kg, fluence 10 J/cm2, fluence rate 50 mW/cm2) alone or in presence of NF-kB or E-Selectin inhibitors (NEMO Binding Domain (NBD) peptide and E-Selectin blocking antibody respectively). For each treatment group, we determined the expression of endothelial adhesion molecules (E-Selectin, ICAM-1, VCAM-1) and the tumor immune infiltrate by immunohistochemistry and flow cytometry. In parallel, the impact of L-PDT on MPM growth and mouse survival were assessed in the presence of E-Selectin inhibition. Results: L-PDT increased the levels of endothelial adhesion molecules E-Selectin, ICAM-1 and VCAM-1 9 to 24 hours after L-PDT treatment in vitro. This was preceded by an increase of IκBα phosphorylation. In the presence of NEMO siRNAs, the expression of NEMO/IKKγ was reduced and led to E-Selectin repression. In orthotopic MPM bearing mice, the treatment of MPM by L-PDT enhanced adhesion molecules expression in tumor vasculature at 24 hours. This correlated with increased infiltration of CD4+ and CD8+ granzyme B+ T-cells and improved tumor control and mouse survival. NF-kB inhibition impaired tumor vascular adhesion molecules upregulation and the recruitment of tumor infiltrating lymphocytes in MPM. The targeted inhibition of E-Selectin abrogated the immune infiltration and tumor regression of MPM following L-PDT, which ultimately decreased animal survival in our MPM model. Conclusion: Low dose PDT relieves MPM tumor vascular anergy via NF-kB mediated adhesion molecules expression. Endothelial E-Selectin has been identified, in our MPM model, as a major determinant for L-PDT enhanced lymphocyte trafficking, tumor control and animal survival. Citation Format: Louis-Emmanuel Chriqui, Yameng Hao, Damien Marie, Michel Gonzalez, Thorsten Krueger, Etienne Meylan, Johanna Joyce, Sabrina Cavin, Jean-Yannis Perentes. Photodynamic therapy promotes immune infiltration and control of malignant pleural mesothelioma through NF-kB mediated upregulation of E-Selectin in the tumor vasculature. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5152.