Prospective Study on Functional Results After Lung-Sparing Radical Pleurectomy in the Management of Malignant Pleural Mesothelioma

Introduction:Malignant pleural mesothelioma (MPM) can reduce lung function by entrapping lung parenchyma via a rind of tumor with or without concurrent effusion. Radical pleurectomy (RP) allows expansion of the trapped lung. The purpose of this study was to investigate changes in pulmonary function and lung perfusion in patients undergoing RP.Methods:In a prospective, nonrandomized study, all patients with histologically proven MPM were evaluated from January to December 2010 for trimodality therapy including RP as surgical procedure. Pulmonary-function tests and perfusion scans were obtained before and 2 months after RP. Primary end points were pulmonary function (forced vital capacity [FVC], forced expiratory volume in 1 second [FEV1]) and ipsilateral lung perfusion.Results:Sixteen out of 25 consecutive patients (age 68.8±8.9 years) were enrolled in the study. Macroscopic complete resection could be achieved in 13 patients (81.3%). Diaphragm resection was necessary in 5 patients. Significant postsurgical improvement of pulmonary function at 2 months was observed for FVC and FEV1 (both absolute and percentage of predicted values) and ipsilateral perfusion (p < 0.001). Avoidance of diaphragm resection was associated with greater increase in FVC (+34.6±17.0% versus +13.5±5.4%; p = 0.002) and FEV1 (+29.2±18.1% versus +12.1±6.4%; p = 0.015), respectively.Conclusions:Lung-sparing RP leads to significant improvement of pulmonary function and perfusion after a recovery time of 2 months. Functional results are better after preservation of the diaphragm. Preservation of physiological reserve via lung-sparing RP might allow patients with MPM to be eligible for further therapeutic options in the long term

Analysis of KRAS Mutations of Exon 2 Codons 12 and 13 by SNaPshot Analysis in Comparison to Common DNA Sequencing

Due to the call for fast KRAS mutation status analysis for treatment of patients with monoclonal antibodies for metastatic colorectal cancer, sensitive, economic, and easily feasible methods are required. Under this aspect, the sensitivity and specificity of the SNaPshot analysis in comparison to the commonly used DNA sequencing was checked. We examined KRAS mutations in exon 2 codons 12 and 13 with DNA sequencing and SNaPshot analysis in 100 formalin-fixed paraffin-embedded tumor tissue samples of pancreatic carcinoma, colorectal carcinoma, and nonsmall cell lung cancer specimens of the primary tumor or metastases. 40% of these samples demonstrated mutated KRAS genes using sequencing and SNaPshot-analysis; additional five samples (45/100) were identified only with the SNaPshot. KRAS mutation detection is feasible with the reliable SNaPshot analysis method. The more frequent mutation detection by the SNaPshot analysis shows that this method has a high probability of accuracy in the detection of KRAS mutations compared to sequencing

Pneumonectomy for Primary Lung Tumors and Pulmonary Metastases: A Comprehensive Study of Postoperative Morbidity, Early Mortality, and Preoperative Clinical Prognostic Factors

Background: Pneumonectomy is a major surgical resection that still remains a high-risk operation. The current study aims to investigate perioperative risk factors for postoperative morbidity and early mortality after pneumonectomy for thoracic malignancies. Methods: We retrospectively analyzed all patients who underwent pneumonectomy for thoracic malignancies at our institution between 2014 and 2022. Complications were assessed up to 30 days after the operation. Mortality for any reason was recorded after 30 days and 90 days. Results: A total of 145 out of 169 patients undergoing pneumonectomy were included in this study. The postoperative 30-day complication rate was 41.4%. The 30-day-mortality was 8.3%, and 90-day-mortality 17.2%. The presence of cardiovascular comorbidities was a risk factor for major cardiopulmonary complications (54.2% vs. 13.2%, p p = 0.029) and American Society of Anesthesiologists (ASA) score 4 (OR: 3.023, 95% CI: 1.028–8.892, p = 0.044) were independent factors for early mortality. Conclusion: Pneumonectomy for thoracic malignancies remains a high-risk major lung resection with significant postoperative morbidity and mortality. Attention should be paid to the preoperative selection of patients

Krebs von den Lungen 6 (KL-6) is a Novel Diagnostic and Prognostic Biomarker in Pleural Mesothelioma

International audienceObjectives: Pleural mesothelioma (PM) is a rare disease with dismal outcome. Systemic treatment options include chemotherapy and immunotherapy, but biomarkers for treatment personalization are missing. The only FDA-approved diagnostic biomarker is the soluble mesothelin-related protein (SMRP). Krebs von den Lungen-6 (KL-6) is a human mucin 1 (MUC1) glycoprotein, which has shown diagnostic and prognostic value as a biomarker in other malignancies. The present study investigated whether KL-6 can serve as a diagnostic and/or prognostic biomarker in PM.Materials and methods: Using a fully-automated chemiluminescence enzyme immunoassay (CLEIA) for KL-6 and SMRP, pleural effusion samples from 87 consecutive patients with PM and 25 patients with non-malignant pleural disorders were studied. In addition, KL-6 and SMRP levels were determined in corresponding patient sera, and in an independent validation cohort (n = 122). MUC1 mRNA and protein expression, and KL-6 levels in cell line supernatants were investigated in PM primary cell lines in vitro.Results: PM patients had significantly higher KL-6 levels in pleural effusion than non-malignant controls (AUC 0.78, p < 0.0001). Among PM patients, levels were highest in those with epithelioid or biphasic histologies. There was a strong positive correlation between pleural effusion levels of KL-6 and SMRP (p < 0.0001). KL-6 levels in sera similarly associated with diagnosis of PM, however, to a lesser extent (AUC 0.71, p = 0.008). PM patients with high pleural effusion KL-6 levels (≥303 IU/mL) had significantly better overall survival (OS) compared to those with low KL-6 levels (HR 0.51, p = 0.004). Congruently, high tumor cell MUC1 mRNA expression in primary cell lines associated with prolonged corresponding patient OS (HR 0.35, p = 0.004). These findings were confirmed in an independent validation cohort.Conclusion: This is the first study demonstrating KL-6 as a potential novel liquid-based diagnostic and prognostic biomarker in PM

LIONS PREY: A New Logistic Scoring System for the Prediction of Malignant Pulmonary Nodules

Objectives: Classifying radiologic pulmonary lesions as malignant is challenging. Scoring systems like the Mayo model lack precision in predicting the probability of malignancy. We developed the logistic scoring system ‘LIONS PREY’ (Lung lesION Score PREdicts malignancY), which is superior to existing models in its precision in determining the likelihood of malignancy. Methods: We evaluated all patients that were presented to our multidisciplinary team between January 2013 and December 2020. Availability of pathological results after resection or CT-/EBUS-guided sampling was mandatory for study inclusion. Two groups were formed: Group A (malignant nodule; n = 238) and Group B (benign nodule; n = 148). Initially, 22 potential score parameters were derived from the patients’ medical histories. Results: After uni- and multivariate analysis, we identified the following eight parameters that were integrated into a scoring system: (1) age (Group A: 64.5 ± 10.2 years vs. Group B: 61.6 ± 13.8 years; multivariate p-value: 0.054); (2) nodule size (21.8 ± 7.5 mm vs. 18.3 ± 7.9 mm; p = 0.051); (3) spiculation (73.1% vs. 41.9%; p = 0.024); (4) solidity (84.9% vs. 62.8%; p = 0.004); (5) size dynamics (6.4 ± 7.7 mm/3 months vs. 0.2 ± 0.9 mm/3 months; p p p = 0.079); and (8) cancer history (34.9% vs. 24.3%; p = 0.052). Our model demonstrated superior precision to that of the Mayo score (p = 0.013) with an overall correct classification of 96.0%, a calibration (observed/expected-ratio) of 1.1, and a discrimination (ROC analysis) of AUC (95% CI) 0.94 (0.92–0.97). Conclusions: Focusing on essential parameters, LIONS PREY can be easily and reproducibly applied based on computed tomography (CT) scans. Multidisciplinary team members could use it to facilitate decision making. Patients may find it easier to consent to surgery knowing the likelihood of pulmonary malignancy. The LIONS PREY app is available for free on Android and iOS devices