Ergonomic Assessment of Robotic versus Thoracoscopic Thymectomy.

Introduction: Robotic and thoracoscopic surgery are being increasingly adopted as minimally invasive alternatives to open sternotomy for complete thymectomy. The superior maneuverability range and three-dimensional magnified vision are potential ergonomical advantages of robotic surgery. To compare the ergonomic characteristics of robotic versus thoracoscopic thymectomy, a previously developed scoring system based on impartial findings was employed. The relationship between ergonomic scores and perioperative endpoints was also analyzed. Methods: Perioperative data of patients undergoing robotic or thoracoscopic complete thymectomy between January 2014 and December 2022 at three institutions were retrospectively retrieved. Surgical procedures were divided into four standardized surgical steps: lower-horns, upper-horns, thymic veins and peri-thymic fat dissection. Three ergonomic domains including maneuverability, exposure and instrumentation were scored as excellent(score-3), satisfactory(score-2) and unsatisfactory(score-1) by three independent reviewers. Propensity score matching (2:1) was performed, including anterior mediastinal tumors only. The primary endpoint was the total maneuverability score. Secondary endpoints included the other ergonomic domain scores, intraoperative adverse events, conversion to sternotomy, operative time, post-operative complications and residual disease. Results: A total of 68 robotic and 34 thoracoscopic thymectomies were included after propensity score matching. The robotic group had a higher total maneuverability score (p = 0.039), particularly in the peri-thymic fat dissection (p = 0.003) and peri-thymic fat exposure score (p = 0.027). Moreover, the robotic group had lower intraoperative adverse events (p = 0.02). No differences were found in residual disease. Conclusions: Robotic thymectomy has shown better ergonomic maneuverability compared to thoracoscopy, leading to fewer intraoperative adverse events and comparable early oncological results.

The modified Lyon's position: an alternative approach to robotic thymectomy.

The conventional supine position for robotic thymectomy may present challenges in accessing the lower thymic horns, particularly in cases requiring extensive resection of mediastinal fat. To address this issue, the authors advocate for a lateral patient position during the procedure, emphasizing optimized access to the thymic horns and improved procedural efficacy. The lateral approach involves specific trocar placements and port arrangements to minimize conflicts between instruments. This report proposes an innovative approach to robotic thymectomy for patients diagnosed with thymoma or thymic hyperplasia associated with myasthenia gravis.

Analysis of predictive factors of unforeseen nodal metastases in resected clinical stage I NSCLC.

Background: Despite notable advances made in preoperative staging, unexpected nodal metastases after surgery are still significantly detected. In this study we aim to analyze the upstaging rate in patients with clinical stage I NSCLC without evidence of nodal disease in the preoperative staging who underwent lobectomy and radical lymphadenectomy. Methods: Patients who underwent lobectomy and systematic lymphadenectomy for clinical stage I NSCLC were evaluated. Exclusion criteria included the neoadjuvant treatment, incomplete resection and no adherence to preoperative guidelines. Results: A total of 297 patients were included in the study. 159 patients were female, and the median age was 68 (61 - 73). The variables that showed a significant correlation with the upstaging rate at the univariate analysis were the number of resected lymph nodes and micropapillar/solid adenocar-cinoma subtype. This result was confirmed in the multivariate analysis with a OR= 2.545 (95%CI 1.136-5.701; p=0.02) for the number of resected lymph nodes and a OR=2.717 (95%CI 1.256-5.875; p=0.01) for the high-grade pattern of adenocarcinoma. Conclusion: Our results showed that in a homogeneous cohort of patients with clinical stage I NSCLC, the number of resected lymph nodes and the histological subtype of adenocarcinoma can significantly be associated with nodal metastasis.

Surgical and survival outcomes with perioperative or neoadjuvant immune-checkpoint inhibitors combined with platinum-based chemotherapy in resectable NSCLC: A systematic review and meta-analysis of randomised clinical trials.

The use of neoadjuvant or perioperative anti-PD(L)1 was recently tested in multiple clinical trials. We performed a systematic review and meta-analysis of randomised trials comparing neoadjuvant or perioperative chemoimmunotherapy to neoadjuvant chemotherapy in resectable NSCLC. Nine reports from 6 studies were included. Receipt of surgery was more frequent in the experimental arm (odds ratio, OR 1.39) as was pCR (OR 7.60). EFS was improved in the experimental arm (hazard ratio, HR 0.55) regardless of stage, histology, PD-L1 expression (PD-L1 negative, HR 0.74) and smoking exposure (never smokers, HR 0.67), as was OS (HR 0.67). Grade > = 3 treatment-related adverse events were more frequent in the experimental arm (OR 1.22). The experimental treatment improved surgical outcomes, pCR rates, EFS and OS in stage II-IIIB, EGFR/ALK negative resectable NSCLC; confirmatory evidence is warranted for stage IIIB tumours and with higher maturity of the OS endpoint.

Robotic Lobectomy without Complete Fissure for Non-Small Cell Lung Cancer: Technical Aspects and Perioperative Outcomes of the Tunnel Technique.

Even though the use of the "fissure-last" technique in mini-invasive lobectomy with the fissureless condition is well accepted, in terms of perioperative outcomes, controversies still surround the hilar lymph node dissection. In this article, we reported a description of the robotic "tunnel technique" approach in the right upper lobectomy in the absence of a defined fissure. We then compared the short terms outcomes of 30 consecutive cases treated using this technique, with 30 patients treated using the "fissure last" VATS approach in the same institution, before the start of the robotic surgery program.

ALK rearrangement is an independent predictive factor of unexpected nodal metastasis after surgery in early stage, clinical node negative lung adenocarcinoma.

OBJECTIVES: Despite notable advances made in preoperative staging, unexpected nodal metastases after surgery are still significantly detected. Given the promising role of neoadjuvant targeted treatments, the definition of novel predictive factors of nodal metastases is an extremely important issue. In this study we aim to analyze the upstaging rate in patients with early stage NSCLC without evidence of nodal disease in the preoperative staging who underwent lobectomy and radical lymphadenectomy. MATERIAL AND METHODS: Patients who underwent lobectomy and systematic lymphadenectomy for early stage LUAD without evidence of nodal disease at the preoperative staging using NGS analysis for actionable molecular targets evaluation after surgery were evaluated. Exclusion criteria included the neoadjuvant treatment, incomplete resection and no adherence to preoperative guidelines. RESULTS: A total of 359 patients were included in the study. 172 patients were female, and the median age was 68 (61-72). The variables that showed a significant correlation with the upstaging rate at the univariate analysis were the ALK rearrangement, the number of resected lymph nodes and the diameter of the tumor. This result was confirmed in the multivariate analysis, with an OR of 8.052 (CI95% 3.123-20.763, p = 0.00001) for ALK rearrangement, 1.087 (CI95% 1.048-1.127, p = 0.00001) for the number of resected nodes and 1.817 (CI95% 1.214-2.719, p = 0.004) for cT status. CONCLUSION: Our results showed that in a homogeneous cohort of patients with clinical node early stage LUAD the ALK rearrangement, the number of resected lymph nodes and the tumor diameter can significantly predict nodal metastasis.

Should EUS-FNA be considered also for the diagnosis of peripheral small pulmonary lesions?

Given the high rate of small lung nodules detected during the oncological follow up for various cancers, in the era of personalize medicine, the histological diagnosis is of paramount importance. Usually, the small peripheral lung nodules are historically reached using a CT guided biopsy but this technique is characterized by an high rate of pneumothorax. Endoscopic procedures were referred only for central tumor that occluded the mains bronchi. In the last few years, the spreading of EBUS-TBNA, EUS-FNA and the navigational bronchoscopy systems has increase the use of these technique also for the diagnosis of small lung nodules.

Multimodal evaluation of locoregional anaesthesia efficacy on postoperative pain after robotic pulmonary lobectomy for NSCLC: a pilot study.

The primary objectives of the study were to analyse the robotic approach and ultrasound-guided paravertebral block compared to thoracoscopic intercostal nerve block after robotic pulmonary lobectomy on postoperative pain and opioids use. The secondary objectives were to analyse and compare patients' necessity of additional antalgic drugs and patients' performance during respiratory therapy, following robotic surgery and in the two groups. Consecutively, 52 patients undergoing robotic pulmonary lobectomies were treated either with ropivacaine-based intercostal nerve block or paravertebral block from February 2022 to October 2022. When necessary, morphine was administered at day 1. Acetaminophen was administered as an additional antalgic drug on demand up to 3 g per day. Pain was measured 1 h after the end of the surgical procedure and daily through the pain numeric rating scale (NRS). Morphine administration rate and per day and total additional administrations of acetaminophen were recorded. Pain and opioids administration was measured 1 month after the procedure. Data were analysed in the overall population and in the intercostal nerve block group VS paravertebral block group. Overall, 34.6% of the patients required morphine administration and 51.7% of the patients required at least daily acetaminophen administration up to discharge. At 1 month postoperatively, four patients presented with chronic pain and one still was under opioid medication. At intergroup analysis, the paravertebral block group demonstrated lower NRS at fixed time points (p < 0.0001) and lower morphine consumption (45.7%VS11.8%; p = 0.02). Acetaminophen rescue administration at fixed time points was lower in the paravertebral block group (p < 0.0001) and mobility and dynamic pain resulted in better results (p = 0.03; p = 0.04). At 1 month, no differences were found between study groups. Similarly to other minimally invasive techniques, postoperative pain may arise after robotic pulmonary lobectomy. Paravertebral bloc can help to reduce postoperative pain as well as morphine and antalgic drugs administration and improve early mobilization.

A prognostic score from a multicentric retrospective analysis of patients affected by sarcoma with metachronous lung metastases undergoing metastasectomy.

BACKGROUND: Despite the lack of evidence-based on prospective randomized studies, surgery has become the cornerstone of the treatment in patients with pulmonary oligometastatic sarcomas. Our study aimed to construct a composite prognostic score for metachronous oligometastatic sarcoma patients. METHODS: A retrospective analysis was performed on data patients who underwent radical surgery for metachronous metastases in six research institutes from January 2010 to December 2018. The log-hazard ratio (HR) obtained from the Cox model was used to derive weighting factors for a continuous prognostic index designed to identify differential outcome risks. RESULTS: A total of 251 patients were enrolled in the study. In the multivariate analysis, a longer disease-free interval (DFI) and a lower neutrophil-to-lymphocytes ratio (NLR) were predictive of a better overall survival (OS) and disease-free survival (DFS). A prognostic score was developed based on DFI and NLR data, identifying 2 risk class groups for DFS (3-years DFS 20.2% for the high-risk group [HRG]and 46.4% for the low-risk group [LRG] [<0.0001]) and 3 risk groups for OS (3 years OS 53.9% for the HRG vs. 76.9% for the intermediate-risk group and 100% of the LRG (p < 0.0001)). CONCLUSION: The proposed prognostic score effectively predicts outcomes for patients with lung metachronous oligo-metastases from the surgically treated sarcoma.

The BNT162b2 mRNA COVID-19 Vaccine Increases the Contractile Sensitivity to Histamine and Parasympathetic Activation in a Human Ex Vivo Model of Severe Eosinophilic Asthma.

The BNT162b2 COVID-19 vaccine is composed of lipid-nanoparticles (LNP) containing the mRNA that encodes for SARS-CoV-2 spike glycoprotein. Bronchospasm has been reported as an early reaction after COVID-19 mRNA vaccines in asthmatic patients. The aim of this study was to investigate the acute impact of BNT162b2 in a human ex vivo model of severe eosinophilic asthma. Passively sensitized human isolated bronchi were challenged with the platelet-activating factor to reproduce ex vivo the hyperresponsiveness of airways of patients suffering from severe eosinophilic asthma. BNT162b2 was tested on the contractile sensitivity to histamine and parasympathetic activation via electrical field stimulation (EFS); some experiments were performed after mRNA denaturation. BNT162b2 increased the resting tone (+11.82 ± 2.27%) and response to histamine in partially contracted tissue (+42.97 ± 9.64%) vs. the control (p < 0.001); it also shifted the concentration-response curve to histamine leftward (0.76 ± 0.09 logarithm) and enhanced the response to EFS (+28.46 ± 4.40%) vs. the control. Denaturation did not significantly modify (p > 0.05) the effect of BNT162b2. BNT162b2 increases the contractile sensitivity to histamine and parasympathetic activation in hyperresponsive airways, a detrimental effect not related to the active component but to some excipient. A possible candidate for the bronchospasm elicited by BNT162b2 could be the polyethylene glycol/macrogol used to produce LNP.

Perioperative outcomes of robotic lobectomy for early-stage non-small cell lung cancer in elderly patients.

Introduction: Minimally invasive surgery has become the standard for the early-stage non-small cell lung cancer (NSCLC). The appropriateness of the kind of lung resection for the elderly patients is still debated. Methods: We retrospectively reviewed patients with older than 75 years who underwent robotic lobectomy between May 2016 to June 2022. We selected 103 patients who met the inclusion criteria of the study. The preoperative cardiorespiratory functional evaluations were collected, and the risk of postoperative complications was calculated according to the Charlson Comorbidity Index, the American College of Surgery surgical risk calculator (ACS-NSQIP), EVAD score, and American Society of Anesthesiology (ASA) score. The patients were divided in two groups according to the presence of postoperative complications. Results: Forty-three patients were female, and 72.8% of the total population were former or active smokers. Thirty-five patients reported postoperative complications. The analysis of the two groups showed that the predicted postoperative forced expiratory volumes in the first second (FEV1) and forced vital capacity (FVC) were significantly lower in patients presenting postoperative complications (p=0.04). Moreover, the upstaging rate and the unexpected nodal metastases were higher in the postoperative complication groups. Conclusion: Robotic-assisted lobectomy for early-stage lung cancer is a safe and feasible approach in selected elderly patients. The factors that could predict the complication rate was the predicted postoperative FEV1 and the nodal disease.

Transesophageal Endoscopic Ultrasound Fine Needle Biopsy for the Diagnosis of Mediastinal Masses: A Retrospective Real-World Analysis.

Background: Endoscopic ultrasound (EUS) plays an important role in the diagnosis and staging of thoracic disease. Our report studies the diagnostic performance and clinical impact of EUS fine needle aspiration (FNA) in a homogenous cohort of patients according to the distribution of the enlarged MLNs or pulmonary masses. Methods: We retrospectively reviewed the diagnostic performance of 211 EUS-FNA in 200 consecutive patients with enlarged or PET-positive MLNs and para-mediastinal masses who were referred to our oncological center between January 2019 and May 2020. Results: The overall sensitivity of EUS-FNA was 85% with a corresponding negative predictive value (NPV) of 56% and an accuracy of 87.5%. The sensitivity and accuracy in patients with abnormal MLNs were 81.1% and 84.4%, respectively. In those with para-mediastinal masses, sensitivity and accuracy were 96.4% and 96.8%. The accuracy for both masses and lymph nodes was 100%, and in the LAG (left adrenal gland), it was 66.6%. Conclusions: Our results show that, in patients with suspected mediastinal masses, EUS-FNA is an accurate technique to evaluate all reachable mediastinal nodal stations, including station 5.

Fluorescence-guided lung nodule identification during minimally invasive lung resections.

In the last few years, minimally invasive surgery has become the standard routine practice to manage lung nodules. Particularly in the case of robotic thoracic surgery, the identification of the lung nodules that do not surface on the visceral pleura could be challenging. Therefore, together with the evolution of surgical instruments to provide the best option in terms of invasiveness, lung nodule localization techniques should be improved to achieve the best outcomes in terms of safety and sensibility. In this review, we aim to overview all principal techniques used to detect the lung nodules that do not present the visceral pleura retraction. We investigate the accuracy of fluorescence guided thoracic surgery in nodule detection and the differences among the most common tracers used.

A Real-World Systematic Analysis of Driver Mutations' Prevalence in Early- and Advanced-Stage NSCLC: Implications for Targeted Therapies in the Adjuvant Setting.

The approval of osimertinib for adjuvant treatment of stage I-II-III EGFR-mutated NSCLC (early stage) represents a paradigm shift, raising the question of whether other genotype-matched therapeutics approved for advanced-stage NSCLC can also provide clinical benefit in the adjuvant setting. However, there is a paucity of real-world data on the prevalence of actionable genomic alterations (GAs) in early-stage NSCLC. We used next-generation sequencing, complemented by immunohistochemistry and fluorescence in situ hybridization, to screen our single-institution cohort of 1961 NSCLC consecutive cases for actionable molecular targets. The prevalence of actionable GAs was comparable in early versus advanced-stage NSCLC, the only exception being KRAS mutations (more frequent in early-stage cases). Consistent with advanced-stage tumors being more aggressive, co-occurrence of TP53 and EGFR GAs as well as copy number gains were less frequent in early-stage tumors. EGFR mutations and high expression of PD-L1 were inversely associated, whereas KRAS mutations and high PD-L1 reactivity showed positive association. Recapitulating advanced-stage tumors, early-stage NSCLC had the highest share of EGFR mutations in lepidic and acinar subtypes. Resected lepidic tumors contained the highest proportion of the KRAS G12C actionable variant. These results, obtained with routine diagnostic technologies in an unselected clinical setting, provide a significant addition of real-world data in early-stage NSCLC.

Long Non-Coding RNAs in the Cell Fate Determination of Neoplastic Thymic Epithelial Cells.

Thymic Epithelial Tumors (TETs) arise from epithelial cells of the thymus and are very rare neoplasms comprising Thymoma, Thymic carcinoma, and Thymic Neuroendocrine tumors that still require in-depth molecular characterization. Long non-coding RNAs (lncRNAs) are emerging as relevant gene expression modulators involved in the deregulation of several networks in almost all types of human cancer, including TETs. LncRNAs act at different control levels in the regulation of gene expression, from transcription to translation, and modulate several pathways relevant to cell fate determination under normal and pathological conditions. The activity of lncRNAs is strongly dependent on their expression, localization, and post-transcriptional modifications. Starting from our recently published studies, this review focuses on the involvement of lncRNAs in the acquisition of malignant traits by neoplastic thymic epithelial cells, and describes the possible use of these molecules as targets for the design of novel therapeutic approaches specific for TET. Furthermore, the involvement of lncRNAs in myasthenia gravis (MG)-related thymoma, which is still under investigation, is discussed.

Analysis of Molecular Biomarkers in Resected Early-Stage Non-Small Cells Lung Cancer: A Narrative Review.

Next-generation sequencing has become a cornerstone in clinical oncology practice and is recommended for the appropriate use of tailored therapies in NSCLC. While NGS has already been standardised in advanced-stage NSCLC, its use is still uncommon in the early stages. The recent approval of Osimertinib for resected EGFR-mutated NSCLC in an adjuvant setting has launched the hypothesis that other targeted therapies used in metastatic patients can also lead to improved early-stage outcomes of NSCLC. The impact of molecular biomarkers on the prognosis of patients undergoing radical surgery for NSCLC is still unclear. Notably, the heterogeneous populations included in the studies that analysed surgical patients could be the main reason for these results. In this review, we report the most important studies that analysed the impact of principal molecular biomarkers on the survival outcomes of patients who underwent radical surgery for NSCLC.