Use of a novel microbiome modulator improves anticancer immunity in a murine model of malignant pleural mesothelioma.

Objective: Malignant pleural mesothelioma is a fatal disease and a clinical challenge, as few effective treatment modalities are available. Previous evidence links the gut microbiome to the host immunoreactivity to tumors. We thus evaluated the impact of a novel microbiome modulator compound (MMC) on the gut microbiota composition, tumor immune microenvironment, and cancer control in a model of malignant pleural mesothelioma. Methods: Age- and weight-matched immunocompetent (n = 23) or athymic BALB/c mice (n = 15) were randomly assigned to MMC or no treatment (control) groups. MMC (31 ppm) was administered through the drinking water 14 days before AB12 malignant mesothelioma cell inoculation into the pleural cavity. The impact of MMC on tumor growth, animal survival, tumor-infiltrating leucocytes, gut microbiome, and fecal metabolome was evaluated and compared with those of control animals. Results: The MMC delayed tumor growth and significantly prolonged the survival of immunocompetent animals (P = .0015) but not that of athymic mice. The improved tumor control in immunocompetent mice correlated with increased infiltration of CD3+CD8+GRZB+ cytotoxic T lymphocytes in tumors. Gut microbiota analyses indicated an enrichment in producers of short chain fatty acids in MMC-treated animals. Finally, we observed a positive correlation between the level of fecal short chain fatty acids and abundance of tumor-infiltrating cytotoxic T cells in malignant pleural mesothelioma. Conclusions: MMC administration boosts antitumor immunity, which correlates with a change in gut microbiome and metabolome. MMC may represent a valuable treatment option to combine with immunotherapy in patients with cancer.

Sleeve lobectomy in patients with non-small-cell lung cancer: a report from the European Society of Thoracic Surgery database 2021.

OBJECTIVES: For centrally located lung tumours, sleeve lobectomy is preferred over pneumectomy. We report on the surgical practices and perioperative outcomes of sleeve resections based on data from 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, neoadjuvant treatments, morbidity and postoperative outcomes of open and video-assisted thoracoscopic surgery (VATS) procedures. RESULTS: In total, 1652 patients (median age: 63 years; females/males: 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 a thoracotomy conversion rate of 21.1% (n = 34); 398 (24.1%) patients received neoadjuvant 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 related to the elevated risk of cardiopulmonary complications were body mass index < 20 [odds ratio (OR): 2.26; P < 0.001] and bilobectomy (OR : 2.28, P < 0.001). Age <60 years (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. Neoadjuvant 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). CONCLUSIONS: Sleeve lobectomies can be safely performed after neoadjuvant treatment. The VATS approach fosters shorter length of stay and decreased morbidity.

Is sleeve lobectomy safe after induction therapy?-a systematic review and meta-analysis.

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 meta-analysis 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.

Prediction of right ventricular failure after left ventricular assist device implantation in patients with heart failure: a meta-analysis comparing echocardiographic parameters.

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.