A Risk Model to Predict the Delivery of Adjuvant Chemotherapy Following Lung Resection in Patients With Pathologically Positive Lymph Nodes.

To investigate factors associated with the ability to receive adjuvant chemotherapy in patients with pathological N1 and N2 stage after anatomic lung resections for non-small cell lung cancer (NSCLC). Multicenter retrospective analysis on 707 consecutive patients found pathologic N1 (pN1) or N2 (pN2) disease following anatomic lung resections for NSCLC (2014-2019). Multiple imputation logistic regression was used to identify factors associated with adjuvant chemotherapy and to develop a model to predict the probability of starting this treatment. The model was externally validated in a population of 253 patients. In the derivation set, 442 patients were pN1 and 265 pN2. 58% received at least 1 cycle of adjuvant chemotherapy. The variables significantly associated with the probability of starting chemotherapy after multivariable regression analysis were: younger age (p < 0.0001), Body Mass Index (BMI) (p = 0.031), Forced Expiratory Volume in 1 second (FEV1) (p = 0.037), better performance status (PS) (p < 0.0001), absence of chronic kidney disease (CKD) (p = 0.016), resection lesser than pneumonectomy (p = 0.010). The logit of the prediction model was: 6.58 -0.112 x age +0.039 x BMI +0.009 x FEV1 -0.650 x PS -1.388 x CKD -0.550 x pneumonectomy. The predicted rate of adjuvant chemotherapy in the validation set was 59.2 and similar to the observed 1 (59%, p = 0.87) confirming the model performance in external setting. This study identified several factors associated with the probability of initiating adjuvant chemotherapy after lung resection in node-positive patients. This information can be used during preoperative multidisciplinary meetings and patients counseling to support decision-making process regarding the timing of systemic treatment.

Surgical resection of Masaoka stage III thymic epithelial tumours with great vessels involvement: a retrospective multicentric analysis from the European Society of Thoracic Surgeons thymic database.

OBJECTIVES: The aim of this study was to analyse the outcomes of an international cohort of patients affected by Masaoka stage III thymic epithelial tumours with vascular involvement and treated by surgery. METHODS: Study design was the observational multicentre retrospective cohort study. Data were extracted from the European Society of Thoracic Surgeons thymic database; additional variables were collected. Inclusion criteria were as follows: stage III (Masaoka-Koga) thymic epithelial tumours; surgery with radical intention; clinical or pathological great vessels involvement; and radiologically suspected or diagnosed intraoperatively. Outcome items were analysed. RESULTS: Sixty-five patients submitted to surgery from 2001 to 2017 fulfilled inclusion criteria. Thymoma and thymic carcinoma patients did not differ for demographics and clinical characteristics. The majority of great vessel treated were superior vena cava or innominate veins (72.3%). Eleven patients (16.9%) had postoperative cardiopulmonary complications; vascular stenosis was observed in 3 patients (4.6%). The multivariable Cox analysis for disease-free survival showed an increased hazard of recurrence for thymic carcinoma (hazard ratio = 3.59; 95% confidence interval: 1.66-7.78, P = 0.001). The 1-, 3-, 5- and 10-year overall survival rates were 0.86, 0.84, 0.81, and 0.53, respectively. There was no significant difference in overall survival according to resection status or between thymoma and thimic carcinoma. The univariable Cox regression model did not show an increased hazard of death for myasthenic patients considering all resection status and for patients who received neoadjuvant therapy. CONCLUSIONS: We observed that clinical outcomes of patients treated for stage III thymic epithelial tumours with vascular involvement are satisfactory suggesting to increase the confidence in dealing with these complex surgeries. Complete resection should be achieved, even though extensive vascular reconstructions are required.

Awake or intubated surgery in diagnosis of interstitial lung diseases? A prospective study.

BACKGROUND: Risks associated with video-assisted surgical lung biopsy (VASLB) for interstitial lung disease (ILD) with endotracheal intubation and mechanical ventilation are not nil. Awake video-assisted surgical lung biopsy (Awake-VASLB) has been proposed as a method to obtain a precise diagnosis in several different thoracic diseases. OBJECTIVES: To compare clinical outcomes of Awake-VASLB and Intubated-VASLB in patients with suspected ILDs. METHODS: From June 2016 to February 2020, all patients submitted to elective VASLB for suspected ILD were included. Differences in outcomes between Awake-VASLB and Intubated-VASLB were assessed through univariable, multivariable-adjusted, and a propensity score-matched analysis. RESULTS: Awake-VASLB was performed in 66 out of 100 patients, while 34 underwent Intubated-VASLB. The Awake-VASLB resulted in a lower post-operative morbidity (OR 0.025; 95% CI 0.001-0.35; p=0.006), less unexpected intensive care unit admission, less need for rescue therapy for pain, a reduced surgical and anaesthesiologic time, a reduced chest drain duration, and a lower post-operative length of stay. CONCLUSION: Awake-VASLB in patients affected by ILD is feasible and seems safer than Intubated-VASLB.

A risk stratification scheme for synchronous oligometastatic non-small cell lung cancer developed by a multicentre analysis.

BACKGROUNDS: Oligometastatic Non-Small Cell Lung Cancer (NSCLC) patients represent a category without a standard therapeutic approach. However, in selected oligometastatic NSCLC, radical surgery seems to offer a good prognosis. This retrospective study aimed to analyse the long-term outcomes of synchronous oligometastatic patients treated with curative intent and identify the factors associated with better results and the proposal of a risk stratification system for classifying the synchronous oligometastatic NSCLC. METHODS: The medical records of patients from 18 centres with pathologically diagnosed synchronous oligometastatic NSCLC were retrospectively reviewed. The inclusion criteria were synchronous oligometastatic NSCLC, radical surgical treatment of the primary tumour with or without neoadjuvant/adjuvant therapy and radical treatment of all metastatic sites. The Kaplan - Meier method estimated survivals. A stratified backward stepwise Cox regression model was assessed for multivariable survival analyses. RESULTS: 281 patients were included. The most common site of metastasis was the brain, in 50.89 % patients. Median overall survival was 40 months (95 % CI: 29-53). Age ≤65 years (HR = 1.02, 95 % CI: 1.00-1.05; p = 0.019), single metastasis (HR = 0.71, 95 % CI: 0.45-1.13; p = 0.15) and presence of contralateral lung metastases (HR = 0.30, 95 % CI: 0.15 - 0.62; p = 0.001) were associated with a good prognosis. The presence of pathological N2 metastases negatively affected survival (HR = 2.00, 95 % CI: 1.21-3.32; p = 0.0065). These prognostic factors were used to build a simple risk classification scheme. CONCLUSIONS: Treatment of selected synchronous oligometastatic NSCLC with curative purpose could be conducted safely and at acceptable 5-year survival levels, especially in younger patients with pN0 disease.

Pulmonary Echinococcosis or Lung Hydatidosis: A Narrative Review.

Background: Lung hydatidosis is a zoonosis related to infection by the Echinococcus tapeworm species. Lung involvement in this condition is second only to the liver echinococcosis. Diagnosis ordinarily results from an accidental finding in a direct chest radiograph evaluation because of the delayed growth of the cysts. Moreover, a consistent treatment regimen or approach may not be feasible because of the variability of pulmonary echinococcosis. In this review, we expect to sum up the main features of lung hydatidosis with a perspective on medical and surgical treatment. Methods: Cochrane Library and PubMed were the databases used to perform a narrative literature review. Search terms included "pulmonary echinococcosis" and "lung hydatidosis." The MeSH terms were "lung" [All Fields] AND {"echinococcosis" [MeSH Terms] OR ("hydatidosis" [All Fields] OR "pulmonary" [All Fields] AND "echinococcosis" [All Fields] OR "hydatidosis." A search period from September 1980 to May 2020 was chosen to compare studies from different decades, given the changes in pulmonary echinococcosis management. Results: A uniform treatment regimen or approach may not be feasible because of the variability of pulmonary echinococcosis. No clinical trials have analyzed and compared all the diverse treatment approaches. Cyst size, characteristics, position in the lung and clinical presentation, and the availability of medical/surgical expertise and equipment are the mainstays of echinococcosis management. When feasible, surgery is as yet the principal therapeutic choice to eliminate the cysts; anti-parasitic drugs may minimize complications during high-risk surgery or be used as definitive therapy in some instances with contraindications to surgery. Conclusions: Lung hydatidosis management must become less heterogeneous. We support treatment directed to the subject established on the clinical scenario, host factors, and surgical risk. Strict cooperation in this process between infectious disease specialists and surgeons may optimize best practices to help create shared practical guidelines to simplify clinicians' decision-making. Furthermore, we need a consensus for lung hydatidosis treatment and inserting this disease to global surgery agenda will have a positive impact on acquiring high-quality data that enables us to create an evidence-based guideline for this disease.

Proctor-guided virtual reality-enhanced three-dimensional video-assisted thoracic surgery: an excellent tutoring model for lung segmentectomy.

OBJECTIVE: Lung segmentectomy using video-assisted thoracoscopic surgery (VATS) is an effective strategy to treat early-stage lung cancer. The objective of this case report is to show the efficacy of Hyper Accuracy 3D™ (HA3D) reconstruction as a tool for trainee surgeons and expert surgeons to perform complex procedures. METHODS: An 84-year-old man was treated for colon-rectal cancer. During follow-up, a pulmonary nodule on the right anterior upper lobe suspected for intestinal metastasis was revealed by a computed tomography scan. According to functional tests and radiology, a right anterior upper lobe segmentectomy was planned. HA3D lung reconstruction was used during surgery. RESULTS: Using the HA3D virtual model, the procedure was performed with healthy tissue sparing, ensuring safe resection margins. No postoperative morbidities were noted. The patient referred good pain control. The hospital stay was 6 days. CONCLUSIONS: VATS segmentectomy is a technically demanding procedure. HA3D lung reconstruction can help surgeons effectively perform the resection, aiding at individuating intersegmental planes, bronchi, and vessels, guaranteeing oncologic radicality and safe surgical margins, and preserving respiratory function.

Kinomic profiling of tumour xenografts derived from patients with non-small cell lung cancer confirms their fidelity and reveals potentially actionable pathways.

INTRODUCTION: High fidelity between non-small cell lung cancer (NSCLC) primary tumours and patient-derived tumour xenografts (PDTXs) is of paramount relevance to spur their application. Extensive proteomic and kinomic analysis of these preclinical models are missing and may inform about their functional status, in terms of phosphopeptides and hyperactive signalling pathways. METHODS: We investigated tumour xenografts derived from patients with NSCLC to identify hyperactive signalling pathways. Fresh tumour fragments from 81 NSCLC surgical samples were implanted in Nod/Scid/Gamma mice, and engrafted tumours were compared with primary specimens by morphology, immunohistochemistry, gene mutation analyses, and kinase activity profiling. Four different tyrosine and serine/threonine kinase inhibitors were tested against primary tumour and PDTX lysates using the PamGene peptide microarray platform. RESULTS: The engraftment rate was 33%, with successful engraftment being more associated with poor clinical outcomes. Genomic profiles led to the recognition of hotspot mutations, some of which were initially undetected in donor samples. Kinomic analyses showed that characteristics of primary tumours were retained in PDTXs, and tyrosine kinase inhibitors (TKIs) responses of individual PDTX lines were either expected, based on the genetic status, or alternatively defined suitable targets unpredictable by single-genome fingerprints. CONCLUSIONS: Collectively, PDTXs mostly resembled their parental NSCLC. Combining genomic and kinomic analyses of tumour xenografts derived from patients with NSCLC, we identified patients' specific targetable pathways, confirming PDTXs as a preclinical tool for biomarker identification and therapeutic algorithm'' improvement.

Potential Diagnostic and Prognostic Role of Microenvironment in Malignant Pleural Mesothelioma.

INTRODUCTION: A comprehensive analysis of the immune cell infiltrate collected from pleural fluid and from biopsy specimens of malignant pleural mesothelioma (MPM) may contribute to understanding the immune-evasion mechanisms related to tumor progression, aiding in differential diagnosis and potential prognostic stratification. Until now such approach has not routinely been verified. METHODS: We enrolled 275 patients with an initial clinical diagnosis of pleural effusion. Specimens of pleural fluids and pleural biopsy samples used for the pathologic diagnosis and the immune phenotype analyses were blindly investigated by multiparametric flow cytometry. The results were analyzed using the Kruskal-Wallis test. The Kaplan-Meier and log-rank tests were used to correlate immune phenotype data with patients' outcome. RESULTS: The cutoffs of intratumor T-regulatory (>1.1%) cells, M2-macrophages (>36%), granulocytic and monocytic myeloid-derived suppressor cells (MDSC; >5.1% and 4.2%, respectively), CD4 molecule-positive (CD4+) programmed death 1-positive (PD-1+) (>5.2%) and CD8+PD-1+ (6.4%) cells, CD4+ lymphocyte activating 3-positive (LAG-3+) (>2.8% ) and CD8+LAG-3+ (>2.8%) cells, CD4+ T cell immunoglobulin and mucin domain 3-positive (TIM-3+) (>2.5%), and CD8+TIM-3+ (>2.6%) cells discriminated MPM from pleuritis with 100% sensitivity and 89% specificity. The presence of intratumor MDSC contributed to the anergy of tumor-infiltrating lymphocytes. The immune phenotype of pleural fluid cells had no prognostic significance. By contrast, the intratumor T-regulatory and MDSC levels significantly correlated with progression-free and overall survival, the PD-1+/LAG-3+/TIM-3+ CD4+ tumor-infiltrating lymphocytes correlated with overall survival. CONCLUSIONS: A clear immune signature of pleural fluids and tissues of MPM patients may contribute to better predict patients' outcome.

Prognostic Value of Exon 19 Versus 21 EGFR Mutations Varies According to Disease Stage in Surgically Resected Non-small Cell Lung Cancer Adenocarcinoma.

BACKGROUND: The prognostic value of exon 19 and 21 EGFR mutations in stage IV non-small cell lung cancer (NSCLC) is well established. OBJECTIVE: We aimed to evaluate the prognostic value of the mutations in surgically resected NSCLC. METHODS: We retrospectively reviewed data from 1798 surgically resected NSCLC adenocarcinomas between 2007 and 2017 in three departments of thoracic surgery (Nancy/Strasbourg, France, and Torino, Italy) for whom mutational status was known. Overall survival (OS) was evaluated using log-rank and Cox proportional hazard models. RESULTS: EGFR exon 19 deletion was observed in 108 patients (55.1%) and exon 21 L858R mutations were observed in 88 patients (44.9%). In stage I, the median OS was not significantly different between exons 19 and 21 (p = 0.54), while, in stage II, the median OS reached 65 months [95% confidence interval (CI) 41.67-88.33] for exon 19 mutations and decreased to 48 months for exon 21 mutations (95% CI 44.21-51.79; p = 0.027). In multivariate analysis, exon 19 deletion remained a favorable prognostic factor [hazard ratio (HR) 0.314, 95% CI 0.098-0.997; p = 0.05]. In stage III, the median OS reached 66 months (95% CI 44.67-87.32) for exon 19 mutations and decreased to 32 months for exon 21 mutations (95% CI 29.86-34.14; p = 0.03). In multivariate analysis, exon 19 deletion remained a significantly favorable prognostic factor (HR 0.165, 95% CI 0.027-0.999; p = 0.05). CONCLUSION: The prognostic value of EGFR exon 19 and 21 mutations appears to be different according to disease stage in surgically resected NSCLC.

KRAS exon 2 codon 13 mutation is associated with a better prognosis than codon 12 mutation following lung metastasectomy in colorectal cancer.

INTRODUCTION: The utilization of molecular markers as routinely used biomarkers is steadily increasing. We aimed to evaluate the potential different prognostic values of KRAS exon 2 codons 12 and 13 after lung metastasectomy in colorectal cancer (CRC). RESULTS: KRAS codon 12 mutations were observed in 116 patients (77%), whereas codon 13 mutations were observed in 34 patients (23%). KRAS codon 13 mutations were associated with both longer time to pulmonary recurrence (TTPR) (median TTPR: 78 months (95% CI: 50.61-82.56) vs 56 months (95% CI: 68.71-127.51), P = 0.008) and improved overall survival (OS) (median OS: 82 months vs 54 months (95% CI: 48.93-59.07), P = 0.009). Multivariate analysis confirmed that codon 13 mutations were associated with better outcomes (TTPR: HR: 0.40 (95% CI: 0.17-0.93), P = 0.033); OS: HR: 0.39 (95% CI: 0.14-1.07), P = 0.07). Otherwise, no significant difference in OS (P = 0.78) or TTPR (P = 0.72) based on the type of amino-acid substitutions was observed among KRAS codon 12 mutations. MATERIALS AND METHODS: We retrospectively reviewed data from 525 patients who underwent a lung metastasectomy for CRC in two departments of thoracic surgery from 1998 to 2015 and focused on 150 patients that had KRAS exon 2 codon 12/13 mutations. CONCLUSIONS: KRAS exon 2 codon 13 mutations, compared to codon 12 mutations, seem to be associated with better outcomes following lung metastasectomy in CRC. Prospective multicenter studies are necessary to fully understand the prognostic value of KRAS mutations in the lung metastases of CRC.

Validation of EORTC and CALGB prognostic models in surgical patients submitted to diagnostic, palliative or curative surgery for malignant pleural mesothelioma.

BACKGROUND: To assess the trend of our surgical patients affected by malignant pleural mesothelioma (MPM) and submitted to diagnostic/palliative or curative surgical procedures and to validate the European Organisation for Research and Treatment of Cancer (EORTC) prognostic score in our patient population. METHODS: This is a cohort study of patients submitted to surgery for MPM from January 2007 to December 2013. Primary outcome was overall survival (OS). Univariate and multivariate-adjusted comparisons by EORTC prognostic score for OS were accomplished using Cox method. Adjusted models included the following clinical variables: kind of procedure, smoking habit, asbestos exposure, Charlson's Comorbidity Index (CCI), clinical tumor stage, adjuvant chemotherapy, dyspnoea, chest pain and haematological variables according to the score features. Nomenclature of the surgical procedures matches the International Association for the Study Lung Cancer (IASLC)/International Mesothelioma Interest Group (iMIG). RESULTS: One-hundred sixty-six consecutive cases were collected: the median age at surgery was 73 years and 123 patients (75%) had a history of asbestos exposure. Ninty patients (54%) were submitted to a palliative/diagnostic thoracoscopy, 30 to pleurectomy/decortication (P/D), and 6 to extra-pleural pneumonectomy (EPP). Clinical TNM stages were as follows: 99 (60%) stage I-II, 34 (20%) stage III and 33 (20%) stage IV. The median follow-up (FU) was 19 months [interquartile range (IQR), 9-31 months] and the FU-completeness was 98%. By the end of the study 130 patients died (78%). One- and 3-year OS was 60% and 36%, respectively. Patients submitted to EPP and P/D showed a better survival (P=0.013). Multivariable model showed an independent prognostic value of EORTC score (HR =2.86, P<0.001). CONCLUSIONS: In selected patients, aggressive surgical approaches, although not radical, may still be beneficial. The EORTC prognostic index proved to be an independent prognostic factor in our cohort of patients and therefore is a reliable and valid instrument that may be implemented in the daily practice.

When size matters: changing opinion in the management of pleural space-the rise of small-bore pleural catheters.

Tube thoracostomy is usually the first step to treat several thoracic/pleural conditions such as pneumothorax, pleural effusions, haemothorax, haemo-pneumothorax and empyema. Today, a wide range of drains is available, ranging from small to large bore ones. Indications for an appropriate selection remains yet matter of debate, especially regarding the use of small bore catheters. Through this paper, we aimed to retrace the improvements of drains through the years and to review the current clinical indications for chest drain placement in pleural/thoracic diseases, comparing the effectiveness of small-bore drains vs. large-bore ones.

Digital versus traditional air leak evaluation after elective pulmonary resection: a prospective and comparative mono-institutional study.

BACKGROUND: The increased demand to reduce costs and hospitalization in general pushed several institution worldwide to develop fast-tracking protocols after pulmonary resections. One of the commonest causes of protracted hospital stay remains prolonged air leaks (ALs). We reviewed our clinical practice with the aim to compare traditional vs. digital chest drainages in order to evaluate which is the more effective to correctly manage the chest tube after pulmonary resection. METHODS: All patients submitted to elective pulmonary resection for lung malignancies, between April to December, 2014 in our General Thoracic Surgery Department were included in the study. The primary outcome was the chest tube duration, the secondary the postoperative overall hospitalization. Significant differences between traditional and digital groups were investigated with logistic regression models. Numerical variables between the groups were compared by means of the unpaired Wilcoxon-Mann-Whitney test. RESULTS: Both series of patients were comparable for clinical, surgical and pathological characteristics. Chest tube duration showed to be significantly shorter in the digital group (3 vs. 5 days, P=0.0009), while the hospitalization was longer in traditional one [8 vs. 7 days in digital drainage (DD); P=0.0385]. No chest drainage replacement was required at 30-day, in both groups. CONCLUSIONS: We were able to demonstrate that patients managed with a digital system experienced a shorter chest tube duration as well as a lower overall hospital length of stay, compared to those who received the traditional drainage (TD).