Circulating cell-free and extracellular vesicles-derived microRNA as prognostic biomarkers in patients with early-stage NSCLC: results from RESTING study.

BACKGROUND: Factors to accurately stratify patients with early-stage non-small cell lung cancer (NSCLC) in different prognostic groups are still needed. This study aims to investigate 1) the prognostic potential of circulating cell-free (CF) and extracellular vesicles (EVs)-derived microRNA (miRNAs), and 2) their added value with respect to known prognostic factors (PFs). METHODS: The RESTING study is a multicentre prospective observational cohort study on resected stage IA-IIIA patients with NSCLC. The primary end-point was disease-free survival (DFS), and the main analyses were carried out separately for CF- and EV-miRNAs. CF- and EV-miRNAs were isolated from plasma, and miRNA-specific libraries were prepared and sequenced. To reach the study aims, three statistical models were specified: one using the miRNA data only (Model 1); one using both miRNAs and known PFs (age, gender, and pathological stage) (Model 2), and one using the PFs alone (Model 3). Five-fold cross-validation (CV) was used to assess the predictive performance of each. Standard Cox regression and elastic net regularized Cox regression were used. RESULTS: A total of 222 patients were enrolled. The median follow-up time was 26.3 (95% CI 25.4-27.6) months. From Model 1, three CF-miRNAs and 21 EV-miRNAs were associated with DFS. In Model 2, two CF-miRNAs (miR-29c-3p and miR-877-3p) and five EV-miRNAs (miR-181a-2-3p, miR-182-5p, miR-192-5p, miR-532-3p and miR-589-5p) remained associated with DFS. From pathway enrichment analysis, TGF-beta and NOTCH were the most involved pathways. CONCLUSION: This study identified promising prognostic CF- and EV-miRNAs that could be used as a non-invasive, cost-effective tool to aid clinical decision-making. However, further evaluation of the obtained miRNAs in an external cohort of patients is warranted.

Phospholipase Family Enzymes in Lung Cancer: Looking for Novel Therapeutic Approaches.

Lung cancer (LC) is the second most common neoplasm in men and the third most common in women. In the last decade, LC therapies have undergone significant improvements with the advent of immunotherapy. However, the effectiveness of the available treatments remains insufficient due to the presence of therapy-resistant cancer cells. For decades, chemotherapy and radiotherapy have dominated the treatment strategy for LC; however, relapses occur rapidly and result in poor survival. Malignant lung tumors are classified as either small- or non-small-cell lung carcinoma (SCLC and NSCLC). Despite improvements in the treatment of LC in recent decades, the benefits of surgery, radiotherapy, and chemotherapy are limited, although they have improved the prognosis of LC despite the persistent low survival rate due to distant metastasis in the late stage. The identification of novel prognostic molecular markers is crucial to understand the underlying mechanisms of LC initiation and progression. The potential role of phosphatidylinositol in tumor growth and the metastatic process has recently been suggested by some researchers. Phosphatidylinositols are lipid molecules and key players in the inositol signaling pathway that have a pivotal role in cell cycle regulation, proliferation, differentiation, membrane trafficking, and gene expression. In this review, we discuss the current understanding of phosphoinositide-specific phospholipase enzymes and their emerging roles in LC.

Oligometastatic breast cancer and metastasis-directed treatment: an aggressive multimodal approach to reach the cure.

Metastatic breast cancer (BC) is considered an incurable disease and is usually treated with palliative intent. However, about 50% of metastatic BCs present with only a few metastatic lesions and are characterized by longer overall survival. These patients, defined as oligometastatic, could benefit from a multimodal approach, which combines systemic therapy with metastasis-directed treatment (stereotactic ablative therapy or surgery). The current definition of oligometastatic seems incomplete since it is based only on imaging findings and does not include biological features, and the majority of relevant data supporting this strategy comes from retrospective or non-randomized studies. However, the chance of reaching long-term complete remission or even a cure has led to the development of randomized trials investigating the impact of combined treatment in oligometastatic BC (OMBC). The SABR-COMET trial, the first randomized study to include BC patients, showed promising results from a combination of stereotactic ablative radiotherapy and systemic therapy. Considering the randomized trial's results, multidisciplinary teams should be set up to select OMBC patients who could achieve long-term survival with aggressive multimodal treatment.

Medical Thoracoscopy and Intrapleural Fibrinolytic Therapy for the Management of Pleural Empyema: A Cohort Study.

BACKGROUND: Pleural empyema is associated with relevant morbidity and mortality, and it may be classified, according to evolution and ultrasound, into three stages: stage I (free-flowing effusion), stage II (viscous effusion with the tendency to loculate), and stage III (organizing phase). According to guidelines, antibiotic therapy and pleural drainage are recommended, with surgery being performed when patients fail and/or in case of organized empyema. OBJECTIVES: The aim of the study was to report the efficacy and safety of medical thoracoscopy in patients with pleural empyema stratified by chest ultrasound. METHOD: Observational retrospective cohort study analyzing patients with pleural empyema treated with medical thoracoscopy. Procedure success and mortality were evaluated at 30 days and 90 days after the procedure; complications were also reported. RESULTS: 131 patients were included. Intrapleural fibrinolytic therapy was performed thereafter in the majority of cases. Medical thoracoscopy was considered successful without subsequent intervention in 99 patients (76%); 19 patients (15%) underwent a second procedure (drainage, thoracoscopy, video-assisted thoracic surgery, or thoracotomy); and 6 patients (5%) died of the evolution of empyema. Patients treated in stages I and II showed significantly better post-procedure results compared with patients treated in stage III (100%, 83.3%, and 58.1%, respectively). Thoracoscopy complications were observed in 18 patients and were reversible in all cases. CONCLUSIONS: Patients with pleural empyema treated in earlier stages (free-flowing or multiloculated effusion) with medical thoracoscopy show significantly better results than patients treated in later stages (organized empyema). This approach is safe, minimally invasive, and efficient in these patients with disease having relevant mortality; however, patient selection remains essential.

The sternum reconstruction: Present and future perspectives.

Sternectomy is a procedure mainly used for removing tumor masses infiltrating the sternum or treating infections. Moreover, the removal of the sternum involves the additional challenge of performing a functional reconstruction. Fortunately, various approaches have been proposed for improving the operation and outcome of reconstruction, including allograft transplantation, using novel materials, and developing innovative surgical approaches, which promise to enhance the quality of life for the patient. This review will highlight the surgical approaches to sternum reconstruction and the new perspectives in the current literature.

Comparative Analysis of Free-Circulating and Vesicle-Associated Plasma microRNAs of Healthy Controls and Early-Stage Lung Cancer Patients.

In recent years, circulating extracellular miRNAs have emerged as a useful tool for the molecular characterization and study of tumors' biological functions. However, the high heterogeneity in sample processing, isolation of circulating fraction, RNA extraction, and sequencing hamper the reproducibility and the introduction of these biomarkers in clinical practice. In this paper, we compare the content and the performance of miRNA sequencing in plasma-derived samples processed with different isolation protocols. We tested three different fractions of miRNA from healthy-donor human blood: whole plasma (WP), free-circulating (FC) and EV-associated, isolated by either column (ccEV) or size exclusion chromatography (secEV) miRNAs. An additional cohort of 18 lung cancer patients was analyzed. Protein profiles of ccEV and secEV were compared and miRNA expression profiles were assessed through sequencing. Slight differences were found between ccEV and secEV expressions of typical EV markers. Conversely, sequencing performance and the mirnome profile varied between RNA extracted using different isolation methods. Sequencing performance was better in FC samples. Higher varieties of miRNAs were identified in WP and FC with respect to ccEV and secEV. Analysis of free-circulating and EV-associated miRNA profiles in lung cancer patients demonstrated the reliability of the biomarkers identifiable on plasma with these approaches.

Biological effects of COVID-19 on lung cancer: Can we drive our decisions.

COVID-19 infection caused by SARS-CoV-2 is considered catastrophic because it affects multiple organs, particularly those of the respiratory tract. Although the consequences of this infection are not fully clear, it causes damage to the lungs, the cardiovascular and nervous systems, and other organs, subsequently inducing organ failure. In particular, the effects of SARS-CoV-2-induced inflammation on cancer cells and the tumor microenvironment need to be investigated. COVID-19 may alter the tumor microenvironment, promoting cancer cell proliferation and dormant cancer cell (DCC) reawakening. DCCs reawakened upon infection with SARS-CoV-2 can populate the premetastatic niche in the lungs and other organs, leading to tumor dissemination. DCC reawakening and consequent neutrophil and monocyte/macrophage activation with an uncontrolled cascade of pro-inflammatory cytokines are the most severe clinical effects of COVID-19. Moreover, neutrophil extracellular traps have been demonstrated to activate the dissemination of premetastatic cells into the lungs. Further studies are warranted to better define the roles of COVID-19 in inflammation as well as in tumor development and tumor cell metastasis; the results of these studies will aid in the development of further targeted therapies, both for cancer prevention and the treatment of patients with COVID-19.

Tracheal reconstruction: mini-review and anatomical study on the use of antero lateral thigh fascial flap for heterotopical transplantation.

Background: The reconstructive tracheal options for extensive lesions still remain limited and although a valid substitute is required unfortunately, the biomechanical tracheal characteristics do not allow an easy replacement. In this study we reviewed the described options and investigated, in human cadaver model, whether thigh fascia can be used, as an alternative to forearm fascia, as recipient site for trachea graft heterotopical allotransplantation. Anatomical study: In three fresh cadavers, 3 tracheal graft, 6 radial forearm (RF) fascial flaps and 6 antero-lateral thigh (ALT) fascial flaps were harvested. For each flap we simulated the heteretopical transplantation of the trachea in each fascial flap, and the harvesting of the composite graft as a free flap. The composite graft was finally decomposed at bench and the pedicle was injected to confirm fascial vascularization. The main measured outcomes were: flap fascia vascularization after pedicle injection, average time of flap harvesting, number of perforators included in ALT fascial flap and diameter of the vessels for anastomosis. Difficulties were noted, in order to compare RF flap and ALT flap. Results: Fascia vascularization was confirmed in all cases by pedicle injection. The main difficulty with radial flap was to harvest the fascial layer due to its thinness and its strong adherence to palmaris longus tendon, while the main difficulty with ALT flap was to prevent any traction on the perforators. The average time of flap harvesting and graft inset (by a junior plastic surgeon) was 1 h and 30 min for radial forearm flap and 2 h and 10 min for ALT flap. Conclusion: Despite many different techniques proposed in the literature, tracheal heterotopical allotransplantation still seemed the most promising, and ALT flap promised be a feasible alternative for heterotopical transplantation of trachea.

Extra Virgin Olive Oil (EVOO), a Mediterranean Diet Component, in the Management of Muscle Mass and Function Preservation.

Aging results in a progressive decline in skeletal muscle mass, strength and function, a condition known as sarcopenia. This pathological condition is due to multifactorial processes including physical inactivity, inflammation, oxidative stress, hormonal changes, and nutritional intake. Physical therapy remains the standard approach to treat sarcopenia, although some interventions based on dietary supplementation are in clinical development. In this context, thanks to its known anti-inflammatory and antioxidative properties, there is great interest in using extra virgin olive oil (EVOO) supplementation to promote muscle mass and health in sarcopenic patients. To date, the molecular mechanisms responsible for the pathological changes associated with sarcopenia remain undefined; however, a complete understanding of the signaling pathways that regulate skeletal muscle protein synthesis and their behavior during sarcopenia appears vital for defining how EVOO might attenuate muscle wasting during aging. This review highlights the main molecular players that control skeletal muscle mass, with particular regard to sarcopenia, and discusses, based on the more recent findings, the potential of EVOO in delaying/preventing loss of muscle mass and function, with the aim of stimulating further research to assess dietary supplementation with EVOO as an approach to prevent or delay sarcopenia in aging individuals.

Phenotypic, functional, and metabolic heterogeneity of immune cells infiltrating non-small cell lung cancer.

Lung cancer is the leading cancer in the world, accounting for 1.2 million of new cases annually, being responsible for 17.8% of all cancer deaths. In particular, non-small cell lung cancer (NSCLC) is involved in approximately 85% of all lung cancers with a high lethality probably due to the asymptomatic evolution, leading patients to be diagnosed when the tumor has already spread to other organs. Despite the introduction of new therapies, which have improved the long-term survival of these patients, this disease is still not well cured and under controlled. Over the past two decades, single-cell technologies allowed to deeply profile both the phenotypic and metabolic aspects of the immune cells infiltrating the TME, thus fostering the identification of predictive biomarkers of prognosis and supporting the development of new therapeutic strategies. In this review, we discuss phenotypic and functional characteristics of the main subsets of tumor-infiltrating lymphocytes (TILs) and tumor-infiltrating myeloid cells (TIMs) that contribute to promote or suppress NSCLC development and progression. We also address two emerging aspects of TIL and TIM biology, i.e., their metabolism, which affects their effector functions, proliferation, and differentiation, and their capacity to interact with cancer stem cells.

Cancer Stem Cells and Cell Cycle Genes as Independent Predictors of Relapse in Non-small Cell Lung Cancer: Secondary Analysis of a Prospective Study.

PURPOSE: Cancer stem cells (CSCs) are described as resistant to chemotherapy and radiotherapy. It has been shown that CSCs influence disease-free survival in patients undergoing surgery for lung cancer (NCT04634630). We recently described an overexpression of CSCs recurrence-related genes (RG) in lung cancer. This study aims to investigate CSC frequency and RG expression as predictors of disease-free survival in lung cancer. EXPERIMENTAL DESIGN: This secondary analysis of a prospective cohort study involved 22 surgical tumor specimens from 22 patients harboring early (I-II) and locally advanced (IIIA) stages ACL and SCCL. Cell population frequency analysis of ALDHhigh (CSCs) and ALDHlow (cancer cells) was performed on each tumor specimen. In addition, RG expression was assessed for 31 target genes separately in ALDHhigh and ALDHlow populations. CSCs frequency and RG expression were assessed as predictors of disease-free survival by Cox analysis. RESULTS: CSCs frequency and RG expression were independent predictors of disease-free survival. CSC frequency was not related to disease-free survival in early-stage patients (HR = 0.84, 95%CI = 0.53-1.33, P = .454), whereas it was a risk factor for locally advanced-stage patients (HR = 1.22, 95%CI = 1.09-1.35, P = .000). RG expression-if measured in CSCs-was related to a higher risk of recurrence (HR = 1.19, 95%CI = 1.03-1.39, P = .021). The effect of RG expression measured in cancer cells on disease-free survival was lower and was not statistically significant (HR = 1.12, 95%CI = 0.94-1.33, P = .196). CONCLUSIONS: CSCs frequency and RG expression are independent predictors of relapse in lung cancer. Considering these results, CSCs and RG may be considered for both target therapy and prognosis.

Second Surgery for Recurrent Malignant Pleural Mesothelioma after Multimodality Treatment: A Systematic Review.

Malignant pleural mesothelioma (MPM) is an aggressive asbestos-related tumour with poor prognosis. To date, a multimodality treatment, including chemotherapy and surgery, with or without radiotherapy, is the gold standard therapy for selected patients with epithelioid and early-stage MPM. In this setting, the goal of surgery is to achieve the macroscopic complete resection, obtained by either extrapleural pneumonectomy or pleurectomy/decortication. Failure, in local and/or distant sites, is one of the major concerns; in fact, there has been no established treatment for the recurrence of MPM after the multimodal approach, and the role of surgery in this context is still controversial. By using electronic databases, studies that included recurrent MPM patients who underwent a second surgery were identified. The endpoints included were: a pattern of recurrence, post-recurrence survival (PRS), and the type of second surgery. When available, factors predicting better PRS and perioperative mortality and morbidity were collected. This systematic review offers an overview of the results that are currently obtained in patients undergoing a second surgery for relapsed MPM, with the aim to provide a comprehensive view on this subject that explores if a second surgery leads to an improvement in survival.

The role of Ivor Lewis esophagectomy in the treatment of achalasia with megaesophagus: A case report.

Introduction: Achalasia with megaesophagus is a pathology characterized by widespread and irregular dilation of the esophageal lumen. In most cases, this dilation is caused by contraction and subsequent failed relaxation of the lower esophageal sphincter (LES). It may be associated with a partial or complete slowing of the esophageal peristalsis. Case overview: We present the case of a 58-year-old woman who developed dysphagia, regurgitation, and substantial weight loss (11 kg) over a span of 1 year. Symptomatic achalasia with megaesophagus was diagnosed following chest and abdominal computed tomography (CT) with contrast and transit RX with gastrografin and esophageal manometry. The patient refuse all minimally endoscopic treatments and opted straightly for the treatment with esophagectomy sec. Ivor-Lewis. At the 6-month follow-up, the patient appeared in excellent general clinical condition and oral gastrografin radiography (OGR) showed good channeling. Discussion: Patients require medical attention when presenting with achalasia that has eroded the esophageal wall enough to form a megaesophagus. Early and minimally invasive treatments (i.e., medical therapy, endoscopic dilation, and myotomy) are insufficient at this stage, and thus esophageal surgery is required. Among the most common surgical approaches, we must mention esophagectomy sec. McKeown and esophagectomy with interposition of a colic loop sec. Wilkins; however, based on our experience, esophagectomy sec. Ivor-Lewis with intrathoracic anastomosis leads to excellent results and can therefore be considered a valid alternative for treating complex cases. Conclusions: Subtotal esophagectomy sec. Ivor-Lewis with intrathoracic anastomosis is effective in treating achalasia with megaesophagus.

Cancer Stem Cells (CSCs), Circulating Tumor Cells (CTCs) and Their Interplay with Cancer Associated Fibroblasts (CAFs): A New World of Targets and Treatments.

The importance of defining new molecules to fight cancer is of significant interest to the scientific community. In particular, it has been shown that cancer stem cells (CSCs) are a small subpopulation of cells within tumors with capabilities of self-renewal, differentiation, and tumorigenicity; on the other side, circulating tumor cells (CTCs) seem to split away from the primary tumor and appear in the circulatory system as singular units or clusters. It is becoming more and more important to discover new biomarkers related to these populations of cells in combination to define the network among them and the tumor microenvironment. In particular, cancer-associated fibroblasts (CAFs) are a key component of the tumor microenvironment with different functions, including matrix deposition and remodeling, extensive reciprocal signaling interactions with cancer cells and crosstalk with immunity. The settings of new markers and the definition of the molecular connections may present new avenues, not only for fighting cancer but also for the definition of more tailored therapies.

The importance of diaphragmatic surgery, chemical pleurodesis and postoperative hormonal therapy in preventing recurrence in catamenial pneumothorax: a retrospective cohort study.

BACKGROUND: Catamenial pneumothorax (CP) is defined as a recurrent, spontaneous pneumothorax occurring within a day before or 72 h after the onset of menstruation. Most first episodes go undiagnosed and treated as primary spontaneous pneumothorax, and only after recurrence is the clinical suspicion of CP raised. No gold-standard management approach exists, especially in terms of managing diaphragmatic involvement. METHODS: This study is a single-centre cohort retrospective study of 24 female patients who underwent surgery for pneumothorax due to diaphragmatic endometriosis between January 2008 and December 2016. Two groups were compared: a group that underwent pleurodesis alone (8 patients) and a group that underwent diaphragmatic surgery and pleurodesis (16 patients). RESULTS: There were differences in BMI and smoking habits between the two groups. The right diaphragm was involved more often (6vs15, p = 0.190). VATS was the preferred surgical approach and only one conversion occurred in the diaphragmatic surgery group (p = 0.470). Diaphragmatic abnormalities were present in all the patients, brown/violet spots (100%) in the pleurodesis group and perforations (100%) in the diaphragmatic surgery group (p < 0.001). There were no differences in days of chest tube removal and length of stay. The recurrence rate was 100% in the pleurodesis alone group while it was only 12.5% in the diaphragmatic surgery group (< 0.001). CONCLUSIONS: In our experience, diaphragmatic surgery and pleurodesis followed by hormonal therapy was an effective approach in preventing recurrence in patients with catamenial pneumothorax and diaphragmatic involvement.

The Influence of Cancer Stem Cells on the Risk of Relapse in Adenocarcinoma and Squamous Cell Carcinoma of the Lung: A Prospective Cohort Study.

PURPOSE: Lung cancer relapse may be associated with the presence of a small population of cancer stem cells (CSCs) with unlimited proliferative potential. Our study assessed the relationship between CSCs and the relapse rate in patients harboring adenocarcinoma (ADL) and squamous cell carcinoma of the lung (SCCL). EXPERIMENTAL DESIGN: This is an observational prospective cohort study (NCT04634630) assessing the influence of CSC frequency on relapse rate after major lung resection in 35 patients harboring early (I-II) (n = 21) and locally advanced (IIIA) (n = 14) ADL and SCCL. There was a 2-year enrollment period followed by a 1-year follow-up period. Surgical tumor specimens were processed, and CSCs were quantified by cytofluorimetric analysis. RESULTS: Cancer stem cells were expressed in all patients with a median of 3.1% of the primary cell culture. Primary analysis showed no influence of CSC frequency on the risk of relapse (hazard ratio [HR] = 1.05, 95% confidence interval [CI] = 0.85-1.30). At secondary analysis, patients with locally advanced disease with higher CSC frequency had an increased risk of relapse (HR = 1.26, 95% CI = 1.14-1.39), whereas this was not observed in early-stage patients (HR = 0.90, 95% CI = 0.65-1.25). CONCLUSION: No association was found between CSC and relapse rates after major lung resection in patients harboring ACL and SCCL. However, in locally advanced-stage patients, a positive correlation was observed between CSC frequency and risk of relapse. These results indicate a need for further molecular investigations into the prognostic role of CSCs at different lung cancer stages. CLINICAL TRIAL REGISTRATION: NCT04634630.

Dissecting Tumor Growth: The Role of Cancer Stem Cells in Drug Resistance and Recurrence.

Emerging evidence suggests that a small subpopulation of cancer stem cells (CSCs) is responsible for initiation, progression, and metastasis cascade in tumors. CSCs share characteristics with normal stem cells, i.e., self-renewal and differentiation potential, suggesting that they can drive cancer progression. Consequently, targeting CSCs to prevent tumor growth or regrowth might offer a chance to lead the fight against cancer. CSCs create their niche, a specific area within tissue with a unique microenvironment that sustains their vital functions. Interactions between CSCs and their niches play a critical role in regulating CSCs' self-renewal and tumorigenesis. Differences observed in the frequency of CSCs, due to the phenotypic plasticity of many cancer cells, remain a challenge in cancer therapeutics, since CSCs can modulate their transcriptional activities into a more stem-like state to protect themselves from destruction. This plasticity represents an essential step for future therapeutic approaches. Regarding self-renewal, CSCs are modulated by the same molecular pathways found in normal stem cells, such as Wnt/ß-catenin signaling, Notch signaling, and Hedgehog signaling. Another key characteristic of CSCs is their resistance to standard chemotherapy and radiotherapy treatments, due to their capacity to rest in a quiescent state. This review will analyze the primary mechanisms involved in CSC tumorigenesis, with particular attention to the roles of CSCs in tumor progression in benign and malignant diseases; and will examine future perspectives on the identification of new markers to better control tumorigenesis, as well as dissecting the metastasis process.

Totally thoracoscopic versus standard VATS lobectomies: perioperative differences.

BACKGROUND: Minimally invasive surgery is considered the gold standard approach for early stage lung cancer. Techniques range from a standard three-port approach to uniportal lobectomies, with no technique emerging as superior thus far. We retrospectively compared the pain outcomes of a standard approach using a utility incision with a totally thoracoscopic technique. METHODS: Between January 2015 and December 2019, 168 patients received a VATS lobectomy in our centers. Two groups were created, Group A (82 patients, totally thoracoscopic approach) and Group B (86 patients, standard approach with utility incision). Perioperative outcomes, such as operative time, complications, length of stay, perioperative and chronic pain using visual analog scale (VAS), and rescue doses of painkillers were examined. A one-way analysis of covariance (ANCOVA) was conducted to investigate the impact of surgical time and days of drainage on VAS score. RESULTS: Pain was less on postoperative day (POD) 1 and 2 (p = 0.025 and p = 0.020, respectively) in Group A. No differences were found in the baseline and perioperative characteristics of the two groups, in the mean VAS score at 1 month (p = 0.429), 1 year (p = 0.561), doses of NSAIDs (p = 0.609), and chronic pain (3vs7 patients, p = 0.220). The ANCOVA test showed no significant effect of surgical time and days of drainage on VAS score (p > 0.05). CONCLUSIONS: In our experience, a totally thoracoscopic approach may improve acute postoperative pain without compromising the oncological results of the procedure and the safety of the patients.

Neoadjuvant PD-1 Inhibitors and Chemotherapy for Locally Advanced NSCLC: A Retrospective Study.

BACKGROUND: Stage III non-small cell lung cancer (NSCLC) encompasses a variety of local invasion and nodal involvement and its management is still under debate. Immune checkpoint inhibitors (ICIs) have been shown to improve the survival in metastatic NSCLC, but are far from being accepted as an induction therapy. METHODS: We retrospectively collected data of all patients who received induction ICIs (nivolumab or pembrolizumab) and chemotherapy (carboplatin with paclitaxel) for stage IIIA-B NSCLC followed by surgery in our unit between January 2019 and March 2020. RESULTS: Of the 12 patients (9 men, 3 women) 6 had a squamous cell carcinoma, 4 had adenocarcinoma, 1 had an undifferentiated adenocarcinoma, and 1 had adeno-squamous carcinoma. Seven patients had stage IIIA disease and 5 had stage IIIB. After induction therapy, 6 patients had stable disease and 6 had a partial response. The median tumor reduction was 3.05 cm (range, 2.30-8.70 cm). All patients, but 1 due to the COVID-19 outbreak, had no delay in surgery. Two patients experienced myelosuppression after induction therapy, 2 had minor adverse effects. Three patients had postoperative complications not related to the induction therapy. All patients had a pathologic response: 5 complete, 4 major, and 3 partial. Eleven patients are alive (mean follow-up, 18.17 ± 4.97 months) and free of disease. CONCLUSIONS: Induction ICI chemotherapy may be a valid treatment in patients with locally advanced NSCLC, providing important tumor downstaging and rendering patients operable. In our experience patients had few side effects and a good pathologic response.

Autologous Blood Pleurodesis: What Is the Optimal Time Interval and Amount of Blood?

BACKGROUND: Air leak is the most common complication after lung resection and leads to increased length of hospital (LOH) stay or patient discharge with a chest tube. Management by autologous blood patch pleurodesis (ABPP) is controversial because few studies exist, and the technique has yet to be standardized. METHODS: We retrospectively reviewed patients undergoing ABPP for prolonged air leak (PAL) following lobectomy in three centers, between January 2014 and December 2019. They were divided into two groups: Group A, 120 mL of blood infused; Group B, 60 mL. Propensity score-matched (PSM) analysis was performed, and 23 patients were included in each group. Numbers and success rates of blood patch, time to cessation of air leak, time to chest tube removal, reoperation, LOH, and complications were examined. Univariate and multivariate analysis of variables associated with an increased risk of air leak was performed. RESULTS: After the PSM, 120 mL of blood is statistically significant in reducing the number of days before chest tube removal after ABPP (2.78 vs. 4.35), LOH after ABPP (3.78 vs. 10.00), and LOH (8.78 vs. 15.17). Complications (0 vs. 4) and hours until air leak cessation (6.83 vs. 3.91, range 1-13) after ABPP were also statistically different (p < 0.05). Air leaks that persisted for up to 13 hours required another ABPP. No patient had re-operation or long-term complications related to pleurodesis. CONCLUSION: In our experience, 120 mL is the optimal amount of blood and the procedure can be repeated every 24 hours with the chest tube clamped.