Extended-sleeve resection for endoluminal recurrence of B3 thymoma: does aerogenous spread really exist?

Thymomas are a variant of thymic epithelial tumors. They are considered malignant due to their tendency to local invasion and they showed lower metastatic behaviour. Distal metastasis are rare and an endobronchial mass is a rare presentation. First-line treatment for early-stage thymomas is surgery; for Masaoka-Koga stage III, neoadjuvant or adjuvant chemoradiation therapy should be considered in association whit surgery after Multidisciplinary Tumour Board (MDT) evaluation. We report a rare case of radical resection with type A extended-sleeve lobectomy in a 63-year-old woman who was affected by endobronchial recurrence of B3 thymoma, 31 months after complete and radical thymectomy.

Pathophysiological Link and Treatment Implication of Heart Failure and Preserved Ejection Fraction in Patients with Chronic Kidney Disease.

Heart failure with preserved ejection fraction (HFpEF) results from a complex interplay of age, genetic, cardiac remodeling, and concomitant comorbidities including hypertension, obesity, diabetes, and chronic kidney disease (CKD). Renal failure is an important comorbidity of HFpEF, as well as a major pathophysiological mechanism for those patients at risk of developing HFpEF. Heart failure (HF) and CKD are intertwined conditions sharing common disease pathways; the so-called "kidney tamponade", explained by an increase in intracapsular pressure caused by fluid retention, is only the latest model to explain renal injury in HF. Recognizing the different phenotypes of HFpEF remains a real challenge; the pathophysiological mechanisms of renal dysfunction may differ across the HF spectrum, as well as the prognostic role. A better understanding of the role of cardiorenal interactions in patients with HF in terms of symptom status, disease progression, and prognosis remains essential in HF management. Historically, patients with HF and CKD have been scarcely represented in clinical trial populations. Current concerns affect the practical approach to HF treatment, and, in this context, physicians are frequently hesitant to prescribe and titrate both new and old treatments. Therefore, the extensive application of HF drugs in diverse HF subtypes with numerous comorbidities and different renal dysfunction etiologies remains a controversial matter of discussion. Numerous recently introduced drugs, such as sodium-glucose-linked transporter 2 inhibitors (SGLT2i), constitute a new therapeutic option for patients with HF and CKD. Because of their protective vascular and hormonal actions, the use of these agents may be safely extended to patients with renal dysfunction in the long term. The present review delves into the phenotype of patients with HFpEF and CKD from a pathophysiological perspective, proposing a treatment approach that suggests a practical stepwise algorithm for the proper application of life-saving therapies in clinical practice.

Robotic thymectomy in thymic tumours: a multicentre, nation-wide study.

OBJECTIVES: Robotic thymectomy has been suggested and considered technically feasible for thymic tumours. However, because of small-sample series and the lack of data on long-term results, controversies still exist on surgical and oncological results with this approach. We performed a large national multicentre study sought to evaluate the early and long-term outcomes after robot-assisted thoracoscopic thymectomy in thymic epithelial tumours. METHODS: All patients with thymic epithelial tumours operated through a robotic thoracoscopic approach between 2002 and 2022 from 15 Italian centres were enrolled. Demographic characteristics, clinical, intraoperative, postoperative, pathological and follow-up data were retrospectively collected and reviewed. RESULTS: There were 669 patients (307 men and 362 women), 312 (46.6%) of whom had associated myasthenia gravis. Complete thymectomy was performed in 657 (98%) cases and in 57 (8.5%) patients resection of other structures was necessary, with a R0 resection in all but 9 patients (98.6%). Twenty-three patients (3.4%) needed open conversion, but no perioperative mortality occurred. Fifty-one patients (7.7%) had postoperative complications. The median diameter of tumour resected was 4 cm (interquartile range 3-5.5 cm), and Masaoka stage was stage I in 39.8% of patients, stage II in 56.1%, stage III in 3.5% and stage IV in 0.6%. Thymoma was observed in 90.2% of patients while thymic carcinoma occurred in 2.8% of cases. At the end of the follow-up, only 2 patients died for tumour-related causes. Five- and ten-year recurrence rates were 7.4% and 8.3%, respectively. CONCLUSIONS: Through the largest collection of robotic thymectomy for thymic epithelial tumours we demonstrated that robot-enhanced thoracoscopic thymectomy is a technically sound and safe procedure with a low complication rate and optimal oncological outcomes.

Case report: Complex left-carina resection: three-year single-center experience.

Carinal and tracheobronchial angle tumors have long been a contraindication for surgical removal; the technique of tracheal sleeve pneumonectomy makes it possible to approach this malignancy but still represents a surgical challenge. Left sleeve pneumonectomy is less common compared with right sleeve pneumonectomy and represents a minority component in the literature's case series due to the complexity of the anatomy. In addition, there is no standard for treatment strategy, and it must be assessed on a case-by-case basis. From 2020 to 2023, we performed three left tracheal sleeve pneumonectomies and one neocarina reconstruction surgery for benign lesions without lung resections. All cases were performed without cardiovascular support such as cardiopulmonary bypass and via median sternotomy. With a median length of stay of 21.5 days (between 14 days and 40 days), all patients were transferred to a physiotherapeutic rehabilitation facility for functional reactivation, where they received physiotherapeutic respiratory therapy given the slow functional recovery. The recorded 30-day mortality was 0. There is no standardized approach for left-sided sleeve pneumonectomy, and it is still a surgical challenge due to intraoperative and postoperative difficulties.

Veno-venous extra-corporeal membrane oxygenation in complex tracheobronchial resection.

Background: Elective extra-corporeal membrane oxygenation (ECMO) is rarely used in thoracic surgery, apart from lung transplantation. The purpose of this study was to summarize our institutional experience with the intraoperative use of veno-venous (VV) ECMO in selected cases of main airway surgery. Methods: We retrospectively analyzed the data of 10 patients who underwent main airway surgery with the support of VV-ECMO between June 2013 and August 2022. Results: Surgical procedures included: three carinal resection and reconstruction with complete preservation of the lung parenchyma, one right upper double-sleeve lobectomy and hemi-carinal resection, and one sleeve resection of the left main bronchus after previous right lower bilobectomy, for thoracic malignancies; four tracheal/carinal repair for extensive traumatic laceration; one extended tracheal resection due to post-tracheostomy stenosis in a patient who had previously undergone a left pneumonectomy. The median intraoperative VV-ECMO use was 162.5 minutes. In three cases with complex resection and reconstruction of the carina and in one case of extended post-tracheostomy stenosis and previous pneumonectomy, high-flow VV-ECMO allowed interruption of ventilation for almost 3 hours. In four patients, VV-ECMO was prolonged in the postoperative period to ensure early extubation. There were no perioperative deaths, no complications related to the use of ECMO and no intraoperative change in the planned type of ECMO. Significant complications occurred only in one patient who developed a small anastomotic dehiscence that led to stenosis and required placement of a Montgomery tube. At the median follow-up of 30 months, all 10 patients were still alive. Conclusions: The use of intraoperative VV-ECMO allows safe and precise performance of main airway surgery with minimal postoperative morbidity in patients requiring complex resections and reconstructions and in cases that cannot be managed with conventional ventilation techniques.

Complex Sleeve Lobectomy Has Lower Postoperative Major Complications Than Pneumonectomy in Patients with Centrally Located Non-Small-Cell Lung Cancer.

BACKGROUND: Standard sleeve lobectomies are recommended over pneumonectomy (PN), but the efficacy and oncological proficiency of complex sleeve lobectomies (CSLs) have not been completely investigated. The aim of this study was to report our experience in CSL in patients affected by a centrally located non-small-cell lung cancer (NSCLC), comparing all the variables and outcomes with PN. METHODS: From 2014 to 2022, we collected the data of patients who underwent PN and CSL for NSCLC, excluding neuroendocrine tumors, salvage surgery or carinal resection. Regression analysis was used to assess the association between procedures and complications; the Kaplan-Meier method and Cox regression analysis were used to evaluate survival and risk factors of reduced survival. RESULTS: We analyzed n = 38 extended sleeve lobectomies and n= 6 double-sleeve lobectomies (CSL group) and n= 60 PNs. We had a trend toward higher postoperative mortality in the PN group (5% vs. 0%, p = 0.13). Major complications and bronchial fistula developed in 21.7% and 6.8% (p = 0.038) and in 6.7% and 4.5% (p = 0.64), respectively. The right side was identified as risk factor for major complications, whereas age > 70 and PN had a trend of association in multivariable analysis. The median OS was similar between the two groups (p = 0.76) and cancer recurrence was the only significant risk factors of reduced OS. Excluding functionally compromised patients, the OS of CSL was better than that of PN (67% vs. 42%, p = 0.25). CONCLUSIONS: Considering that major complications are often associated with mortality after surgery for centrally located NSCLC, CSLs could be considered an alternative to PN while also ensuring comparable survival.

National Multicenter Study on the Comparison of Robotic and Open Thymectomy for Thymic Neoplasms in Myasthenic Patients: Surgical, Neurological and Oncological Outcomes.

Thymectomy is the gold standard in the treatment of thymic neoplasm and plays a key role in the therapeutic path of myasthenia gravis. For years, sternotomy has been the traditional approach for removing anterior mediastinal lesions, although the robotic thymectomy is now widely performed. The literature is still lacking in papers comparing the two approaches and evaluating long-term oncological and neurological outcomes. This study aims to analyze the postoperative results of open and robotic thymectomy for thymic neoplasms in myasthenic patients. Surgical, oncological and neurological data of myasthenic patients affected by thymic neoplasms and surgically treated with extended thymectomy, both with the open and the robotic approach, in six Italian Thoracic Centers between 2011 and 2021 were evaluated. A total of 213 patients were enrolled in the study: 110 (51.6%) were treated with the open approach, and 103 (48.4%) were treated with robotic surgery. The open surgery, compared with the robotic, presented a shorter operating time (p < 0.001), a higher number of postoperative complications (p = 0.038) and longer postoperative hospitalization (p = 0.006). No other differences were observed in terms of surgical, oncological or neurological outcomes. The robotic approach can be considered safe and feasible, comparable to the open technique, in terms of surgical, oncological and neurological outcomes.

A Multicenter Retrospective Case-Control Study on Simple vs Extended Sleeve Lobectomies.

BACKGROUND: Sleeve resection is currently the gold standard procedure for centrally located non-small cell lung cancer (NSCLC). Extended sleeve lobectomy (ESL) consists of an atypical bronchoplasty with resection of >1 lobe and carries several technical difficulties compared with simple sleeve lobectomy (SSL). Our study compared the outcomes of ESL and SSL for NSCLC. METHODS: This multicenter, retrospective, cohort study included 1314 patients who underwent ESL (155 patients) or SSL (1159 patients) between 2000 and 2018. The primary end points were 30-day and 90-day mortality, overall survival (OS), disease-free survival (DFS), and complications. RESULTS: No differences were found between the 2 groups in general characteristics and surgical and survival outcomes. In particular, there were no differences in early and late complication frequency, 30- and 90-day mortality, R status, recurrence, OS (54.26 ± 33.72 months vs 56.42 ± 32.85 months, P = .444), and DFS (46.05 ± 36.14 months vs 47.20 ± 35.78 months, P = .710). Mean tumor size was larger in the ESL group (4.72 ± 2.30 cm vs 3.81 ± 1.78 cm, P < .001). Stage IIIA was the most prevalent stage in ESL group (34.8%), whereas stage IIB was the most prevalent in SSL group (34.3%; P < .001). The multivariate analyses found nodal status was the only independent predictive factor for OS. CONCLUSIONS: ESL gives comparable short- and long-term outcomes to SSL. Appropriate preoperative staging and exclusion of metastases to mediastinal lymph nodes, as well as complete (R0) resection, are essential for good long-term outcomes.

Presentation and treatment of two massive intrapericardial lipoma. Case report.

INTRODUCTION AND IMPORTANCE: Primary pericardial tumors are very rare with an overall incidence of 0.001-0.007 % and account for approximately 10 % of heart neoplasms. We present two clinical cases of massive mature intrapericardial lipomas (maximum size 270 × 230 mm) that were successfully treated in our department. CASE PRESENTATION: The first case is that of a 67-year-old male patient who underwent diagnostic investigations after the onset of dyspnea, which confirmed an intrapericardial mass of 270 × 230 mm in size that extended into the left lung field and was treated surgically by a clamshell incision. The second case is that of a 48-year-old patient who was completely asymptomatic and occasionally confirmed to have a 170 × 110 mm intrapericardial mass around the heart, which was surgically removed via sternotomy, also resulting in a mature lipoma. CLINICAL DISCUSSION: In asymptomatic patients with small lesions, close monitoring is generally indicated. In asymptomatic patients with large lesions the decision should be made after multidisciplinary (MDT) evaluation. In symptomatic patients, surgical treatment is indicated. Lipomas are usually mature lesions with a capsule connected to the origin structure by one or more pedicles. Once reached the cardiac level and opened the pericardium, attention must be paid in resecting these pedicles given the area of origin and the possibility that they may be associated with vital structures. CONCLUSION: Both cases were characterized by slow recovery of normal cardiac function in the postoperative course. The average length of patient stay was 12 days, and one case was noted for readmission because a slight increase in pericardial effusion was detected at the scheduled ultrasound check after discharge. After further expert evaluation and steriodine therapy, the patient was discharged to a healthy home after 5 days. This report aims to describe the decision-making process, successful surgical treatment and outcomes of two rare massive intrapericardial tumors.

Effect of colchicine on perioperative atrial fibrillation and myocardial injury after non-cardiac surgery in patients undergoing major thoracic surgery (COP-AF): an international randomised trial.

BACKGROUND: Higher levels of inflammatory biomarkers are associated with an increased risk of perioperative atrial fibrillation and myocardial injury after non-cardiac surgery (MINS). Colchicine is an anti-inflammatory drug that might reduce the incidence of these complications. METHODS: COP-AF was a randomised trial conducted at 45 sites in 11 countries. Patients aged 55 years or older and undergoing major non-cardiac thoracic surgery were randomly assigned (1:1) to receive oral colchicine 0·5 mg twice daily or matching placebo, starting within 4 h before surgery and continuing for 10 days. Randomisation was done with use of a computerised, web-based system, and was stratified by centre. Health-care providers, patients, data collectors, and adjudicators were masked to treatment assignment. The coprimary outcomes were clinically important perioperative atrial fibrillation and MINS during 14 days of follow-up. The main safety outcomes were a composite of sepsis or infection, and non-infectious diarrhoea. The intention-to-treat principle was used for all analyses. This trial is registered with ClinicalTrials.gov, NCT03310125. FINDINGS: Between Feb 14, 2018, and June 27, 2023, we enrolled 3209 patients (mean age 68 years [SD 7], 1656 [51·6%] male). Clinically important atrial fibrillation occurred in 103 (6·4%) of 1608 patients assigned to colchicine, and 120 (7·5%) of 1601 patients assigned to placebo (hazard ratio [HR] 0·85, 95% CI 0·65 to 1·10; absolute risk reduction [ARR] 1·1%, 95% CI -0·7 to 2·8; p=0·22). MINS occurred in 295 (18·3%) patients assigned to colchicine and 325 (20·3%) patients assigned to placebo (HR 0·89, 0·76 to 1·05; ARR 2·0%, -0·8 to 4·7; p=0·16). The composite outcome of sepsis or infection occurred in 103 (6·4%) patients in the colchicine group and 83 (5·2%) patients in the placebo group (HR 1·24, 0·93-1·66). Non-infectious diarrhoea was more common in the colchicine group (134 [8·3%] events) than the placebo group (38 [2·4%]; HR 3·64, 2·54-5·22). INTERPRETATION: In patients undergoing major non-cardiac thoracic surgery, administration of colchicine did not significantly reduce the incidence of clinically important atrial fibrillation or MINS but increased the risk of mostly benign non-infectious diarrhoea. FUNDING: Canadian Institutes of Health Research, Accelerating Clinical Trials Consortium, Innovation Fund of the Alternative Funding Plan for the Academic Health Sciences Centres of Ontario, Population Health Research Institute, Hamilton Health Sciences, Division of Cardiology at McMaster University, Canada; Hanela Foundation, Switzerland; and General Research Fund, Research Grants Council, Hong Kong.

Awake uniportal VATS sublobar lung resections in high-comorbidity patients: Single-center early post-operative outcomes.

Introduction: Awake minimally invasive Uniportal Video Assisted Thoracic Surgery (U-VATS) represents the last challenge in thoracic surgery that could change the future scenario for high comorbidity patients with early-stage non-small cell lung cancer (NSCLC). We report a single center preliminary experience of awake thoracoscopic uni-portal anatomic and non-anatomic sub-lobar resections in this setting. Methods: We retrospectively analyzed data collected on a prospective database of patients undergoing U-VATS awake sub-lobar lung resections for NSCLC between September 2021 and September 2022. Inclusion criteria were clinical stage I disease; contraindication to standard lobectomy due to high respiratory function impairment; general anesthesia considered at high risk based on the American Society of Anesthesiologist score and on the Charlson Comorbidity Index. All patients underwent a standardized awake non-intubated anesthesia protocol approved by our institutional board. Results: They were n = 10 patients: n = 8 wedge resections; n = 2 segmentectomies. We had n = 1 (10%) conversion to standard general anesthesia and n = 1 laryngeal mask support but maintaining spontaneous breathing. N = 5 patients (50%) needed an Intensive Care Unit recovery (mean time = 17.20 h). Mean chest tube duration and Hospital stay were 2.0 and 3.5 days respectively. We did not register 30- days postoperative mortality. Conclusion: Awake thoracic surgery is a feasible technique, and it could be performed also in high comorbidities' patients without a high rate of complications and allows to operate patients that so far were considered borderline for surgery.

Video-assisted transcervical-transtracheal repair of posterior wall laceration of thoracic trachea: A new approach. Case Report.

Iatrogenic tracheal lacerations are a rare but potentially fatal event. In selected acute cases, surgery plays a key role. Treatment can be conservative, for lacerations of less than 3 cm; surgical or endoscopic, depending on the size and location of the lesion and fan efficiency. There is no clear indication of the use of any of these approaches and the decision is therefore linked to local expertise. We present an emblematic clinical case of a 79 years old female patient undergoing polytrauma as a result of a road accident, without neurological damage, which required intubation and subsequent tracheotomy due to a significant limitation to ventilation. Imaging has shown the tracheal laceration involving the anterior wall and the pars membranacea up to the origin of the right main bronchus.A percutaneous tracheotomy was permormed without any improvement of the respiratory dynamic. Therefore, the patient underwent a surgical repair of the tracheal laceration with a hybrid mini-cervicotomic/endoscopic approach. This less invasive approach successfully repaired the extensive loss of substance.

Does thoracoscopic basal pyramid segmentectomy really offer functional advantages in comparison with thoracoscopic lower lobectomy?

OBJECTIVES: The functional impact of thoracoscopic basal segmentectomy in comparison with lower lobectomy has not been investigated in-depth and the aim of this study was to clarify this topic. METHODS: We retrospectively analysed a cohort of patients who underwent surgery between 2015 and 2019 for non-small-cell lung cancer, peripherally located lung nodules, far enough from both the apical segment and the lobar hilum to allow an oncologically safe thoracoscopic lower lobectomy or basal segmentectomy. Pulmonary function tests (PFTs) including spirometry and plethysmography were performed 1 month after surgery and forced expiratory volume in 1 s, forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO) were collected; the difference, the loss and the recovery rate of pulmonary function were calculated and compared with the Wilcoxon-Mann-Whitney test. RESULTS: During the study period, n = 45 and n = 16 patients for video-assisted thoracoscopic surgery (VATS) lower lobectomy and for VATS basal segmentectomy, respectively, completed the study protocol: the 2 groups were homogeneous as to preoperative variables and PFT values. Postoperative outcomes were similar and PFTs revealed significant differences between postoperative forced expiratory volume in 1 s %, FVC%, ΔFVC and ΔFVC%. The loss percentage of FVC%, DLCO% and the recovery rate was better for FVC and DLCO in the VATS basal segmentectomy group. CONCLUSIONS: Thoracoscopic basal segmentectomy seems to be associated with a more preserved lung function, maintaining more FVC and DLCO levels than lower lobectomy, and could be performed in selected cases ensuring also adequate oncological margins.

Rationale and design of the colchicine for the prevention of perioperative atrial fibrillation in patients undergoing major noncardiac thoracic surgery (COP-AF) trial.

BACKGROUND: Perioperative atrial fibrillation (AF) and myocardial injury after noncardiac surgery (MINS) are common complications after noncardiac surgery. Inflammation has been implicated in the pathogenesis of both disorders. The COP-AF trial tests the hypothesis that colchicine reduces the incidence of perioperative AF and MINS in patients undergoing major noncardiac thoracic surgery. METHODS AND RESULTS: The 'COlchicine for the Prevention of Perioperative Atrial Fibrillation' (COP-AF) trial is an international, blinded, randomized trial that compares colchicine to placebo in patients aged at least 55 years and undergoing major noncardiac thoracic surgery with general anesthesia. Exclusion criteria include a history of AF and a contraindication to colchicine (eg, severe renal dysfunction). Oral colchicine at a dose of 0.5 mg or matching placebo is given within 4 hours before surgery. Thereafter, patients receive colchicine 0.5 mg or placebo twice daily for a total of 10 days. The 2 independent co-primary outcomes are clinically important perioperative AF (including atrial flutter) and MINS during 14 days of follow-up. The main safety outcomes are sepsis or infection and non-infectious diarrhea. We aim to enroll 3,200 patients from approximately 40 sites across 11 countries to have at least 80% power for the independent evaluation of the 2 co-primary outcomes. The COP-AF main results are expected in 2023. CONCLUSIONS: COP-AF is a large randomized and blinded trial designed to determine whether colchicine reduces the risk of perioperative AF or MINS in patients who have major noncardiac thoracic surgery.

Challenges in the treatment of small cell lung cancer in the era of immunotherapy and molecular classification.

For many years the standard of care for small cell lung cancer (SCLC) has remained unchanged. Despite decades of active research, current treatment options are limited and the prognosis of patients with extended disease (ED) SCLC remains poor. The introduction of immune checkpoint inhibitors (ICIs) represents an exception and the only recent approval for ED-SCLC. However, the magnitude of benefit obtained with immunotherapy in SCLC is much more modest than that observed in other malignancies. Different pro-immunogenic or immunosuppressive features within the tumor microenvironment of SCLC may either modulate the sensitivity to immunotherapy or conversely dampen the efficacy of ICIs. Beside immunotherapy, a deeper understanding of the molecular biology of SCLC has led to the identification of new therapeutic targets for this lethal malignancy. Recent epigenetic and gene expression studies have resulted into a new molecular classification of four distinct subtypes of SCLC, defined by the relative expression of key transcription regulators and each characterized by specific therapeutic vulnerabilities. This review discusses the rationale for immunotherapy in SCLC and summarizes the main ICIs-trials in this tumor. We provide also an overview of new potential therapeutic opportunities and their integration with the new molecular classification of SCLC.

Post-operative and early oncological results of simple and complex full thoracoscopic segmentectomies for non-small-cell lung cancer.

BACKGROUND: The role of video-assisted thoracoscopic segmentectomy in the treatment of clinical IA non-small-cell lung cancer is not well established. The aim of our retrospective analysis was to evaluate the oncological results of complex and simple video-assisted thoracoscopic segmentectomy. METHODS: From 2015 to June 2020, data of n = 163 consecutive patients undergoing video-assisted thoracoscopic segmentectomy for solitary pulmonary nodule were analysed. The Kaplan-Meier method, log-rank test and Cox regression were used to estimate, compare survivals and identify risk factors of worse oncological outcomes. RESULTS: In this period, n = 123 patients underwent video-assisted thoracoscopic segmentectomy for non-small-cell lung cancer: we performed n = 65 simple and n = 58 complex video-assisted thoracoscopic segmentectomy; n = 99 (80.5%) had a solid appearance on computed tomography scan and n = 78 (63.4%) a moderate-to-high [18F]-2-fluoro-2-deoxy-D-glucose (FDG)-positron emission tomographic computed tomography scan avidity. Mortality was 0%, and complications occurred in n = 14 (21.5%) and 9 (15.5%) patients. The median follow-up was 24 (range: 6-60) months and the 5-year overall survival was 96% without difference between video-assisted thoracoscopic segmentectomies (p = 0.16). Local recurrence developed in n = 2 (3.1%) and n = 3 (5.2%) patients; regional in n = 2 (3.1%) and 1 (1.8%) and distant in 8 (12.3%) and 2 (3.4%), without difference between video-assisted thoracoscopic segmentectomies (p = 0.51). The overall 5-year disease-free survival rate was 78%. Pathological upstaging was observed in n = 13 patients (nodal in n = 6, tumour in n = 7) and it was the only significant factor for worse disease-free survival at the multivariable analysis (hazard ratio: 2.43, 95% CI: 1.04-8.68, p = 0.049), value confirmed also in the group of intended video-assisted thoracoscopic segmentectomy (p = 0.047). CONCLUSIONS: Pathological upstaging after simple or complex video-assisted thoracoscopic segmentectomy is a risk factor for recurrence and then video-assisted thoracoscopic segmentectomy should be considered an appropriate therapeutic option for selected stage IA non-small-cell lung cancer patients.

KRAS G12 isoforms exert influence over up-front treatments: A retrospective, multicenter, Italian analysis of the impact of first-line immune checkpoint inhibitors in an NSCLC real-life population.

Background: KRAS is commonly mutated in non-small cell lung cancer (NSCLC); however, the prognostic and predictive impact of each G12 substitution has not been fully elucidated. The approval of specific G12C inhibitors has modified the idea of KRAS "undruggability", and although the first-line standard consists of immune checkpoint inhibitors (ICIs) with or without chemotherapy, as suggested at ASCO 2022, the outcome in KRAS-mutated population is still controversial. Methods: We retrospectively described the clinical and pathological characteristics of a homogeneous G12 mutated cohort of 219 patients treated in four Italian oncologic units. We evaluated the outcome (PFS at 18 months and OS at 30 months) of those who underwent standard first-line treatment according to PD-L1 status, focusing on differences across single mutations. Results: In the study population, 47.9% of patients harbor the KRAS G12C mutation; 20.5%, G12V; 17.4%, G12D; and 8.2%, G12A. Smoking was a common behavior of patients harboring transversions and transition mutations. PD-L1 expression does not show particular distribution in the case series, although we recorded a prevalence of PD-L1 <1% in G12V (51.4%) compared to G12A (26.7%). ICIs alone was the clinician's choice in 32.7% of patients, and the chemo-immune combination in 17.3% of patients. We described the independent prognostic role of young age (p = 0.007), female gender (p = 0.016), and an ICI-based regimen (p = 0.034) regardless of mutations. Overall, our data confirm the worst prognostic value of G12V mutation apart from treatment choice unlike the other major mutations (C, D, and A) that showed a favorable trend in PFS. Conclusions: KRAS G12 mutations are confirmed to have different characteristics, and the outcome is influenced by ICI first-line regimen. This study provides valuable information for further analysis in the future.

Lung Cancer Immunotherapy: Beyond Common Immune Checkpoints Inhibitors.

Immunotherapy is an ever-expanding field in lung cancer treatment research. Over the past two decades, there has been significant progress in identifying immunotherapy targets and creating specific therapeutic agents, leading to a major paradigm shift in lung cancer treatment. However, despite the great success achieved with programmed death protein 1/ligand 1 (PD-1/PD-L1) monoclonal antibodies and with anti-PD-1/PD-L1 plus anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4), only a minority of lung cancer patients respond to treatment, and of these many subsequently experience disease progression. In addition, immune-related adverse events sometimes can be life-threatening, especially when anti-CTLA-4 and anti-PD-1 are used in combination. All of this prompted researchers to identify novel immune checkpoints targets to overcome these limitations. Lymphocyte activation gene-3 (LAG-3), T cell immunoglobulin (Ig) and Immunoreceptor Tyrosine-Based Inhibitory Motif (ITIM) domain (TIGIT), T cell immunoglobulin and mucin-domain containing-3 (TIM-3) are promising molecules now under investigation. This review aims to outline the current role of immunotherapy in lung cancer and to examine efficacy and future applications of the new immune regulating molecules.

Markers of Bronchiolitis Obliterans Syndrome after Lung Transplant: Between Old Knowledge and Future Perspective.

Bronchiolitis obliterans syndrome (BOS) is the most common form of CLAD and is characterized by airflow limitation and an obstructive spirometric pattern without high-resolution computed tomography (HRCT) evidence of parenchymal opacities. Computed tomography and microCT analysis show abundant small airway obstruction, starting from the fifth generation of airway branching and affecting up to 40-70% of airways. The pathogenesis of BOS remains unclear. It is a multifactorial syndrome that leads to pathological tissue changes and clinical manifestations. Because BOS is associated with the worst long-term survival in LTx patients, many studies are focused on the early identification of BOS. Markers may be useful for diagnosis and for understanding the molecular and immunological mechanisms involved in the onset of BOS. Diagnostic and predictive markers of BOS have also been investigated in various biological materials, such as blood, BAL, lung tissue and extracellular vesicles. The aim of this review was to evaluate the scientific literature on markers of BOS after lung transplant. We performed a systematic review to find all available data on potential prognostic and diagnostic markers of BOS.