Autoimmunity in thymic epithelial tumors: a not yet clarified pathologic paradigm associated with several unmet clinical needs.

Thymic epithelial tumors (TETs) are rare mediastinal cancers originating from the thymus, classified in two main histotypes: thymoma and thymic carcinoma (TC). TETs affect a primary lymphoid organ playing a critical role in keeping T-cell homeostasis and ensuring an adequate immunological tolerance against "self". In particular, thymomas and not TC are frequently associated with autoimmune diseases (ADs), with Myasthenia Gravis being the most common AD present in 30% of patients with thymoma. This comorbidity, in addition to negatively affecting the quality and duration of patients' life, reduces the spectrum of the available therapeutic options. Indeed, the presence of autoimmunity represents an exclusion criteria for the administration of the newest immunotherapeutic treatments with checkpoint inhibitors. The pathophysiological correlation between TETs and autoimmunity remains a mystery. Several studies have demonstrated the presence of a residual and active thymopoiesis in adult patients affected by thymomas, especially in mixed and lymphocytic-rich thymomas, currently known as type AB and B thymomas. The aim of this review is to provide the state of art in regard to the histological features of the different TET histotype, to the role of the different immune cells infiltrating tumor microenvironments and their impact in the break of central immunologic thymic tolerance in thymomas. We discuss here both cellular and molecular immunologic mechanisms inducing the onset of autoimmunity in TETs, limiting the portfolio of therapeutic strategies against TETs and greatly impacting the prognosis of associated autoimmune diseases.

Integrating AI-Powered Digital Pathology and Imaging Mass Cytometry Identifies Key Classifiers of Tumor Cells, Stroma, and Immune Cells in Non-Small Cell Lung Cancer.

Artificial intelligence (AI)-powered approaches are becoming increasingly used as histopathologic tools to extract subvisual features and improve diagnostic workflows. On the other hand, hi-plex approaches are widely adopted to analyze the immune ecosystem in tumor specimens. Here, we aimed at combining AI-aided histopathology and imaging mass cytometry (IMC) to analyze the ecosystem of non-small cell lung cancer (NSCLC). An AI-based approach was used on hematoxylin and eosin (H&E) sections from 158 NSCLC specimens to accurately identify tumor cells, both adenocarcinoma and squamous carcinoma cells, and to generate a classifier of tumor cell spatial clustering. Consecutive tissue sections were stained with metal-labeled antibodies and processed through the IMC workflow, allowing quantitative detection of 24 markers related to tumor cells, tissue architecture, CD45+ myeloid and lymphoid cells, and immune activation. IMC identified 11 macrophage clusters that mainly localized in the stroma, except for S100A8+ cells, which infiltrated tumor nests. T cells were preferentially localized in peritumor areas or in tumor nests, the latter being associated with better prognosis, and they were more abundant in highly clustered tumors. Integrated tumor and immune classifiers were validated as prognostic on whole slides. In conclusion, integration of AI-powered H&E and multiparametric IMC allows investigation of spatial patterns and reveals tissue relevant features with clinical relevance. SIGNIFICANCE: Leveraging artificial intelligence-powered H&E analysis integrated with hi-plex imaging mass cytometry provides insights into the tumor ecosystem and can translate tumor features into classifiers to predict prognosis, genotype, and therapy response.

Acquisition of suppressive function by conventional T cells limits antitumor immunity upon Treg depletion.

Regulatory T (Treg) cells contribute to immune homeostasis but suppress immune responses to cancer. Strategies to disrupt Treg cell-mediated cancer immunosuppression have been met with limited clinical success, but the underlying mechanisms for treatment failure are poorly understood. By modeling Treg cell-targeted immunotherapy in mice, we find that CD4+ Foxp3- conventional T (Tconv) cells acquire suppressive function upon depletion of Foxp3+ Treg cells, limiting therapeutic efficacy. Foxp3- Tconv cells within tumors adopt a Treg cell-like transcriptional profile upon ablation of Treg cells and acquire the ability to suppress T cell activation and proliferation ex vivo. Suppressive activity is enriched among CD4+ Tconv cells marked by expression of C-C motif receptor 8 (CCR8), which are found in mouse and human tumors. Upon Treg cell depletion, CCR8+ Tconv cells undergo systemic and intratumoral activation and expansion, and mediate IL-10-dependent suppression of antitumor immunity. Consequently, conditional deletion of Il10 within T cells augments antitumor immunity upon Treg cell depletion in mice, and antibody blockade of IL-10 signaling synergizes with Treg cell depletion to overcome treatment resistance. These findings reveal a secondary layer of immunosuppression by Tconv cells released upon therapeutic Treg cell depletion and suggest that broader consideration of suppressive function within the T cell lineage is required for development of effective Treg cell-targeted therapies.

Percutaneous Computed Tomography (CT)-Guided Localization with Indocyanine Green for the Thoracoscopic Resection of Small Pulmonary Nodules.

BACKGROUND: The identification of small lung nodules is challenging during mini-invasive thoracic surgery. Unable to palpate them directly, surgeons have developed several methods to preoperatively localize pulmonary nodules, including the computed tomography-guided positioning of coils or metallic landmarks (hook wire) or bronchoscopic marking. METHODS: We present a series of patients scheduled for the video-assisted thoracoscopic sublobar resection of small pulmonary nodules, in which we performed preoperative percutaneous computed tomography (CT)-guided nodule localization through the injection of a mixture of indocyanine green and human albumin. RESULTS: A total of 40 patients underwent a preoperative CT-guided injection of indocyanine green followed by VATS resection within 24 h. Patients tolerated the procedure well, no pain medication was administrated, and no complications were observed during the marking procedure. All pulmonary nodules were easily detected and successfully resected. CONCLUSION: the near-infrared dye marking solution of indocyanine green (ICG) with diluted human albumin was safe, effective, and easy to perform. The ICG solution has the potential to facilitate the accurate localization and resection of pulmonary nodules during VATS surgery, avoiding the risk of marker displacement/migration.

Blood-Derived Systemic Inflammation Markers and Risk of Nodal Failure in Stage Ia Non-Small Cell Lung Cancer: A Multicentric Study.

BACKGROUND: Unexpected spread to regional lymph nodes can be found in up to 10% of patients with early stage non-small cell lung cancer (NSCLC), thereby affecting both prognosis and treatment. Given the known relation between systemic inflammation and tumor progression, we sought to evaluate whether blood-derived systemic inflammation markers might help to the predict nodal outcome in patients with stage Ia NSCLC. METHODS: Preoperative levels of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic inflammation score (SII, platelets × NLR) were collected from 368 patients who underwent curative lung resection for NSCLC. After categorization, inflammatory markers were subjected to logistic regression and time-event analysis in order to find associations with occult nodal spread and postoperative nodal recurrence. RESULTS: No inflammation marker was associated with the risk of occult nodal spread. SII showed a marginal effect on early nodal recurrence at a quasi-significant level (p = 0.065). However, patients with T1c tumors and elevated PLR and/or SII had significantly shorter times to nodal recurrence compared to T1a/T1b patients (p = 0.001), while patients with T1c and normal PLR/SII did not (p = 0.128). CONCLUSIONS: blood-derived inflammation markers had no value in the preoperative prediction of nodal status. Nevertheless, our results might suggest a modulating effect of platelet-derived inflammation markers on nodal progression after the resection of tumors larger than 2 cm.

Analysis of Risk Factors for Tracheal Stenosis Managed during COVID-19 Pandemic: A Retrospective, Case-Control Study from Two European Referral Centre.

INTRODUCTION: Benign subglottic/tracheal stenosis (SG/TS) is a life-threatening condition commonly caused by prolonged endotracheal intubation or tracheostomy. Invasive mechanical ventilation was frequently used to manage severe COVID-19, resulting in an increased number of patients with various degrees of residual stenosis following respiratory weaning. The aim of this study was to compare demographics, radiological characteristics, and surgical outcomes between COVID-19 and non-COVID patients treated for tracheal stenosis and investigate the potential differences between the groups. MATERIALS AND METHODS: We retrospectively retrieved electronical medical records of patients managed at two referral centers for airways diseases (IRCCS Humanitas Research Hospital and Avicenne Hospital) with tracheal stenosis between March 2020 and May 2022 and grouped according to SAR-CoV-2 infection status. All patients underwent a radiological and endoscopic evaluation followed by multidisciplinary team consultation. Follow-up was performed through quarterly outpatient consultation. Clinical findings and outcomes were analyzed by using SPPS software. A significance level of 5% (p < 0.05) was adopted for comparisons. RESULTS: A total of 59 patients with a mean age of 56.4 (±13.4) years were surgically managed. Tracheal stenosis was COVID related in 36 (61%) patients. Obesity was frequent in the COVID-19 group (29.7 ± 5.4 vs. 26.9 ± 3, p = 0.043) while no difference was found regarding age, sex, number, and types of comorbidities between the two groups. In the COVID-19 group, orotracheal intubation lasted longer (17.7 ± 14.5 vs. 9.7 ± 5.8 days, p = 0.001), tracheotomy (80%, p = 0.003) as well as re-tracheotomy (6% of cases, p = 0.025) were more frequent and tracheotomy maintenance was longer (21.5 ± 11.9 days, p = 0.006) when compared to the non-COVID group. COVID-19 stenosis was located more distal from vocal folds (3.0 ± 1.86 vs. 1.8 ± 2.03 cm) yet without evidence of a difference (p = 0.07). The number of tracheal rings involved was lower in the non-COVID group (1.7 ± 1 vs. 2.6 ± 0.8 p = 0.001) and stenosis were more frequently managed by rigid bronchoscopy (74% vs. 47%, p = 0.04) when compared to the COVID-19 group. Finally, no difference in recurrence rate was detected between the groups (35% vs. 15%, p = 0.18). CONCLUSIONS: Obesity, a longer time of intubation, tracheostomy, re-tracheostomy, and longer decannulation time occurred more frequently in COVID-related tracheal stenosis. These events may explain the higher number of tracheal rings involved, although we cannot exclude the direct role of SARS-CoV-2 infection in the genesis of tracheal stenosis. Further studies with in vitro/in vivo models will be helpful to better understand the role of inflammatory status caused by SARS-CoV-2 in upper airways.

Phenotypic diversity of T cells in human primary and metastatic brain tumors revealed by multiomic interrogation.

The immune-specialized environment of the healthy brain is tightly regulated to prevent excessive neuroinflammation. However, after cancer development, a tissue-specific conflict between brain-preserving immune suppression and tumor-directed immune activation may ensue. To interrogate potential roles of T cells in this process, we profiled these cells from individuals with primary or metastatic brain cancers via integrated analyses on the single-cell and bulk population levels. Our analysis revealed similarities and differences in T cell biology between individuals, with the most pronounced differences observed in a subgroup of individuals with brain metastasis, characterized by accumulation of CXCL13-expressing CD39+ potentially tumor-reactive T (pTRT) cells. In this subgroup, high pTRT cell abundance was comparable to that in primary lung cancer, whereas all other brain tumors had low levels, similar to primary breast cancer. These findings indicate that T cell-mediated tumor reactivity can occur in certain brain metastases and may inform stratification for treatment with immunotherapy.

Muscle and Muscle-like Autoantigen Expression in Myasthenia Gravis Thymus: Possible Molecular Hint for Autosensitization.

The thymus is widely recognized as an immunological niche where autoimmunity against the acetylcholine receptor (AChR) develops in myasthenia gravis (MG) patients, who mostly present thymic hyperplasia and thymoma. Thymoma-associated MG is frequently characterized by autoantibodies to the muscular ryanodine receptor 1 (RYR1) and titin (TTN), along with anti-AChR antibodies. By real-time PCR, we analyzed muscle-CHRNA1, RYR1, and TTN-and muscle-like-NEFM, RYR3 and HSP60-autoantigen gene expression in MG thymuses with hyperplasia and thymoma, normal thymuses and non-MG thymomas, to check for molecular changes potentially leading to an altered antigen presentation and autoreactivity. We found that CHRNA1 (AChR-α subunit) and AIRE (autoimmune regulator) genes were expressed at lower levels in hyperplastic and thymoma MG compared to the control thymuses, and that the RYR1 and TTN levels were decreased in MG versus the non-MG thymomas. Genes encoding autoantigens that share epitopes with AChR-α (NEFM and HSP60), RYR1 (neuronal RYR3), and TTN (NEFM) were up-regulated in thymomas versus hyperplastic and control thymuses, with distinct molecular patterns across the thymoma histotypes that could be relevant for autoimmunity development. Our findings support the idea that altered muscle autoantigen expression, related with hyperplastic and neoplastic changes, may favor autosensitization in the MG thymus, and that molecular mimicry involving tumor-related muscle-like proteins may be a mechanism that makes thymoma prone to developing MG.

Early Hospital Discharge on Day Two Post Robotic Lobectomy with Telehealth Home Monitoring: A Pilot Study.

Despite the adoption of enhanced recovery programs, the reported postoperative length of stay after robotic surgery is 4 days even in highly specialized centers. We report preliminary results of a pilot study for a new protocol of early discharge (on day 2) with telehealth home monitoring after robotic lobectomy for lung cancer. All patients with a caregiver were discharged on postoperative day 2 with a telemonitoring device if they satisfied specific discharge criteria. Teleconsultations were scheduled once in the afternoon of post-operative day 2, twice on postoperative day 3, and then once a day until the chest tube removal. Post-discharge vital signs were recorded by patients at least four times daily through the device and were available for consultation by two surgeons through phone application. In case of sudden variation of vital signs or occurrence of adverse events, a direct telephone line was available for patients as well as a protected re-hospitalization path. Primary outcome was the safety evaluated by the occurrence of post-discharge complications and readmissions. Secondary outcome was the evaluation of resources optimization (hospitalization days) maintaining the standard of care. During the study period, twelve patients satisfied all preoperative clinical criteria to be enrolled in our protocol. Two of twelve enrolled patients were successively excluded because they did not satisfy discharge criteria on postoperative day 2. During telehealth home monitoring a total of 27/427 vital-sign measurements violated the threshold in seven patients. Among the threshold violations, only 1 out of 27 was a critical violation and was managed at home. No postoperative complication occurred neither readmission was needed. A mean number of three hospitalization days was avoided and an estimated economic benefit of about EUR 500 for a single patient was obtained if compared with patients submitted to VATS lobectomy in the same period. These preliminary results confirm that adoption of telemonitoring allows, in selected patients, a safe discharge on postoperative day 2 after robotic surgery for early-stage NSCLC. A potential economic benefit could derive from this protocol if this data will be confirmed in larger sample.

What Is the Appropriate Timing for Bar Removal After the Nuss Repair for Pectus Excavatum?

INTRODUCTION: The Nuss procedure for pectus excavatum requires that the sternal elevation be maintained by indwelling metal bars that are traditionally removed approximately 3 y after the repair. METHODS: A retrospective cohort study was conducted of all patients who underwent primary Nuss repair from 2007 to 2018 in two institutions and had a follow-up of at least 24 mo. Pectus bars had been left in place beyond 3 y in patients concerned over possible recurrence after bar removal. Structured interviews were held to assess pain, chest tightness, or other discomfort, and any adverse events related to pectus bars. Results were compared between patients in whom pectus bars were removed after 3 y (standard group) and those in whom bars were left in place longer (extended bar duration group). RESULTS: Two hundred and thirty-one patients (91% males, mean age 23.9 ± 8.3, mean Haller index 4.9 ± 2.3) were included. Bar duration was 30.6 ± 6.6 mo in the standard group (51 patients) versus 69.1 ± 26.3 mo in the extended group (180 patients). Some discomfort was reported by 81.6% in the standard group versus 62.9% in the extended group (P = 0.033), and discomfort occurring at least monthly or more often was only reported by 30% in the standard versus 30.3% in the extended group (P = 1.000). Quality of life improved in 92.6% of the standard group versus 94.7% of the extended group (P = 1.000). No significant adverse events were reported in either group. CONCLUSIONS: Our data suggest that an extended bar duration after the Nuss repair may not cause any adverse event nor negatively affect quality of life.

The Development of an Intelligent Agent to Detect and Non-Invasively Characterize Lung Lesions on CT Scans: Ready for the "Real World"?

(1) Background: Once lung lesions are identified on CT scans, they must be characterized by assessing the risk of malignancy. Despite the promising performance of computer-aided systems, some limitations related to the study design and technical issues undermine these tools' efficiency; an "intelligent agent" to detect and non-invasively characterize lung lesions on CT scans is proposed. (2) Methods: Two main modules tackled the detection of lung nodules on CT scans and the diagnosis of each nodule into benign and malignant categories. Computer-aided detection (CADe) and computer aided-diagnosis (CADx) modules relied on deep learning techniques such as Retina U-Net and the convolutional neural network; (3) Results: Tests were conducted on one publicly available dataset and two local datasets featuring CT scans acquired with different devices to reveal deep learning performances in "real-world" clinical scenarios. The CADe module reached an accuracy rate of 78%, while the CADx's accuracy, specificity, and sensitivity stand at 80%, 73%, and 85.7%, respectively; (4) Conclusions: Two different deep learning techniques have been adapted for CADe and CADx purposes in both publicly available and private CT scan datasets. Experiments have shown adequate performance in both detection and diagnosis tasks. Nevertheless, some drawbacks still characterize the supervised learning paradigm employed in networks such as CNN and Retina U-Net in real-world clinical scenarios, with CT scans from different devices with different sensors' fingerprints and spatial resolution. Continuous reassessment of CADe and CADx's performance is needed during their implementation in clinical practice.

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.

Single-Center 20-Year Experience in Surgical Treatment of Malignant Pleural Mesothelioma.

Objectives: We examined a series of malignant pleural mesothelioma (MPM) patients who consecutively underwent surgery in our institution during the last 20 years. Across this period, we changed our surgical approach to MPM, adopting extended pleurectomy and decortication (eP/D) instead of extrapleural pneumonectomy (EPP). In this study, we compare the perioperative outcomes and long-term survival of patients who underwent EPP vs. eP/D. Methods: A retrospective analysis was carried out of all the MPM patients identified from our departmental database who underwent EPP or P/D from 2000 to 2021. Clavien−Dindo criteria was adopted to score postoperative complications, while Kaplan−Meier methods and a Cox multivariable analysis were used to perform the survival analysis. Results: Of 163 patients, 78 (48%) underwent EPP and 85 (52%) eP/D. Induction chemotherapy was significantly administrated more often in the eP/D group (88% vs. 51%). Complete trimodality treatment including induction chemotherapy, radical surgery, and adjuvant radiotherapy was administered in 74% of the eP/D group versus 32% of the EPP group (p < 0.001). The postoperative morbidity rate was higher in the eP/D group (54%) compared to the EPP group (36%) (p = 0.02); no statistically significant differences were identified concerning major complications (EPP 43% vs. eP/D 24%, p = 0.08). No statistical differences were identified in 30-day mortality, 90-day mortality, median disease-free, and overall survival statistics between the two groups. The Cox multivariable analysis confirmed no induction chemotherapy (HR, 0.5; p = 0.002), RDW (HR, 1.08; p = 0.02), and the presence of pathological nodal disease (HR, 1.99; p = 0.001) as factors associated with worse survival in the entire series. Conclusions: Our data support that eP/D is a well-tolerated procedure allowing the implementation of a trimodality strategy (induction chemotherapy, surgery, and radiotherapy) in most MPM patients. When eP/D is offered in this setting, the oncological results are comparable to EPP. To obtain the best oncological results, the goal of surgical resection should be macroscopic complete resection (R0) in carefully selected patients (clinical N0).

Thymomectomy versus complete thymectomy in early-stage non-myasthenic thymomas: a multicentric propensity score-matched study.

OBJECTIVES: Thymomectomy is gaining consensus over complete thymectomy in early-stage thymoma without myasthenia gravis. This is due both to the difficulty of establishing prospective and randomized controlled studies and to the lack of well-defined selection criteria. This bicentric, retrospective propensity score-matched study aims at comparing oncological outcomes, measured in terms of overall survival and thymoma-related survival, in patients undergoing either thymomectomy or complete thymectomy. METHODS: We retrospectively analysed medical records of patients with clinical early-stage (I and II) thymoma undergoing thymomectomy or complete thymectomy. Exclusion criteria were the presence of myasthenia gravis, clinical advanced tumours and thymic carcinoma. A propensity score-matching analysis was applied to reduce potential preoperative selection biases such as comorbidity (Charlson score), tumour maximal diameter and surgical approach (open versus minimal). All variables were dichotomized. RESULTS: A total of 255 patients were enrolled from 2 different Hospitals, 126 underwent complete thymectomy and 129 a thymomectomy. Disease-free and thymoma-related survivals showed a 5-year rate of 87.7% and 96.0% and a 10-year rate of 82.2% and 91.9%, respectively. Propensity score-matching analysis selected a total of 176 patients equally divided between the 2 groups. No difference was found for both disease-free (P = 0.11) and thymoma-related (P = 0.37) survival in the 2 groups of resection. Multivariable Cox regression analysis showed that histology (P < 0.001), residual disease (P < 0.001) and adjuvant chemotherapy (P < 0.001) were the only predictors of shorter disease-free survival. Whereas there was no evidence to confirm that disease-free and thymoma-related survivals were influenced by resection extent. CONCLUSIONS: Thymomectomy is an adequate surgical resection for non-myasthenic thymoma, achieving disease-free and thymoma-related survivals comparable to those after complete thymectomy.

Preoperative CT-Guided Near-Infrared Dye Marking for Thoracoscopic Resection of Pulmonary Nodules: A Case Report.

Localization of small-sized pulmonary nodules is challenging during video-assisted thoracoscopic surgery. Several preoperative strategies have been developed to mark these targets. We describe our localization strategy using a preoperative computed tomography-guided near-infrared dye marking.

Bronchoscopic Intra-Pleural Instillation of Fibrin Glue and Autologous Blood to Manage Persistent Air Leaks after Lung Resection.

Background: Persistent air leak is a common complication after lung resection causing prolonged length of stay and increased healthcare costs. Surgical intervention can be an option, but other more conservative approaches should be considered first. Here, we describe the use of flexible bronchoscopy to apply fibrin glue and autologous blood sequentially to the damaged lung. We named the technique "flexible thoracoscopy". METHODS: Medical records from patients with persistent air leaks after lung resection were collected retrospectively. Depending on the type of aerostasis that was performed, two groups were created: flexible thoracoscopy and surgery (thoracotomy). Flexible thoracoscopy was introduced at our institution in 2013. We entered the pleural space with a bronchoscope following the same surgical pathway that was used for tube thoracostomy. Perioperative characteristics and outcomes were analyzed using R software (ver. 3.4.4). RESULTS: From 1997 to 2021, a total of 23 patients required an intervention for persistent air leaks. Aerostasis was performed via flexible thoracoscopy in seventeen patients (69%) and via thoracotomy in six patients (31%). The median age was 70 years (22-82). Twenty patients were males (87%). There was no difference in age, sex distribution, BMI, comorbidities and FEV1%. An ASA score of 3 was more represented in the flexible thoracoscopy group; however, no evidence of a difference was found when compared to the thoracotomy group (p = 0.124). Length of in-hospital stay and chest tube duration was also similar between groups (p = 1 and p = 0.68, respectively). CONCLUSIONS: Aerostasis achieved either by flexible thoracoscopy or by thoracotomy showed similar results. We believe that flexible thoracoscopy could be a valid alternative to facilitate minimally invasive treatments for persistent air leaks. Further studies are needed to confirm these results.

Robotic and Video-Assisted Thoracic Surgery for Early-Stage Lung Cancer: Comparison of Long-Term Pain at a Single Centre.

BACKGROUNDS: Since the application of mini-invasive surgery to pulmonary lobectomy, various studies confirmed the feasibility and the safety of the technique, with equivalent oncological standards. However, there are no studies that compare long-term postoperative pain in minimally invasive thoracic surgery. METHODS: Between 1 January 2019 and 28 February 2020, we analysed pain scores at 2 weeks, 3 months, 6 months, and 1 year after the operation, where 50 patients underwent a VATS lobectomy and 50 underwent a RATS lobectomy. Pain scores are obtained through a telephone questionnaire, according to a Numerical Rating Scale (NRS). RESULTS: The medias of the NRS scores, at 2 weeks, 3 months, 6 months, and 1 year after the operation were similar in both groups. Group I was composed of 50 patients who underwent a video-assisted lobectomy, while Group II was composed of 50 patients who underwent a robotic-assisted lobectomy. Two weeks after surgery Group I had a NRS value of 2.96 and in Group II it was 2.86; three months after in Group I the value was 2.16 and in Group II it was 2.06; six months after Group I 's value was 1.62 and Group II's was 1.56; one year after in Group I the value was 1.30 and in the Group II was 1.24. For each time interval, no statistically significant differences were found (p > 0.05). CONCLUSIONS: In our analysis, RATS and VATS did not have significant differences in post-operative and long-term pain.

Efficacy of Intraoperative Hypertonic Glucose Solution Administration on Persistent Air Leak After Extended Pleurectomy/Decortication for Malignant Pleural Mesothelioma: A Retrospective Case-Control Study.

BACKGROUND: Persistent air leak is a common complication occurring from 6% to 23% of cases after extended pleurectomy/decortication for malignant pleural mesothelioma. Treatment options for this complication after major lung resection are well documented in literature; nevertheless, lines of evidence in extended pleurectomy/decortication for malignant pleural mesothelioma are absent. The aim of the study is to evaluate the efficacy of intraoperative administration of 50% hypertonic glucose solution in reducing duration of air leak following extended pleurectomy/decortication for malignant pleural mesothelioma. MATERIALS AND METHODS: In this retrospective case-control study, we analyzed our electronic health record and selected those patients with a histological diagnosis of malignant pleural mesothelioma who underwent extended pleurectomy/decortication in the period 2013-2021. From 2018, we introduced a lavage with 500 ml of glucose solution at 50% concentration into the chest cavity at the end of the surgical procedure. Patients operated before 2018 were used as the control group. Postoperative glycemia was measured, and patients were followed after hospital discharge until the air leak resolved and the chest tube was removed. Statistical analysis was performed using R software. RESULTS: A total of 71 patients met our criteria. Treatment and control groups were similar for age, sex, smoking status, number of comorbidities, tumor histotype, and side of disease. Use of hypertonic glucose solution resulted in shorter chest tube maintenance after hospital discharge (p = 0.0028). A statistically significant difference (p = 0.02) was also found in postoperative glycemia between the treatment (103 g/dl ± 8.9) and control group (98.8 g/dl ± 8.6). Days of hospitalization and chest tube maintenance during hospitalization did not significantly differ between the groups. INTERPRETATION: Intraoperative administration of 50% hypertonic glucose solution reduced the duration of air leak after hospital discharge. An increase in postoperative glycemia was found in the treatment group, but with no clinical effect. Hypertonic glucose solution is an effective and safe method to manage persistent air leak after extended pleurectomy/decortication for malignant pleural mesothelioma.

Extended Pleurectomy/Decortication for Malignant Pleural Mesothelioma: Humanitas's Experience.

BACKGROUND: We analysed a series of malignant pleural mesothelioma (MPM) patients who consecutively underwent extended Pleurectomy/Decortication (eP/D) in a centre with a high level of thoracic surgery experience (IRCCS Humanitas Research Hospital) to explore postoperative morbidity and mortality, pattern of recurrence and survival. METHODS: A retrospective analysis was performed on MPM patients underwent eP/D in our centre from 2010 to 2021. All patients were identified from our departmental database. Postoperative complications were scored according to Clavien-Dindo criteria. Survival analysis was performed by the Kaplan-Meier methods and Cox multivariable analysis. RESULTS: Eighty-five patients underwent extended pleurectomy decortication (eP/D) during study period. Macroscopical residual disease (R2) was reported in one case. A neoadjuvant chemotherapy regiment was administrated in 88% of the surgical cohort. A complete trimodality treatment including induction with platinum agents and pemetrexed, radical cytoreductive surgery and volumetric modulated arc therapy technology (VMAT) could be administered in 63 patients (74%). Postoperative morbidity rate was 54.11%, major complications (defined as Clavien-Dindo ≥ 3) were reported in 11 patients (12.9%). Thirty-day mortality and 90-day mortality were, respectively, 2.35% and 3.53%. Median disease-free and overall survival were, respectively, 13.7 and 25.5 months. The occurrence of major complications (Clavien-Dindo ≥ 3), operative time, pT3-T4, pathological node involvement (pN+) were prognostic factors associated with worse survival. CONCLUSIONS: In our experience, eP/D is a well-tolerated procedure with acceptable mortality and morbidity, allowing for the administration of trimodality regimens in most patients. eP/D offered in a multimodality treatment setting have satisfactory long term oncological results. To obtain best oncological results the goal of surgery should be macroscopic complete resection in carefully selected patients (clinical N0).

Radiomics and gene expression profile to characterise the disease and predict outcome in patients with lung cancer.

OBJECTIVE: The objectives of our study were to assess the association of radiomic and genomic data with histology and patient outcome in non-small cell lung cancer (NSCLC). METHODS: In this retrospective single-centre observational study, we selected 151 surgically treated patients with adenocarcinoma or squamous cell carcinoma who performed baseline [18F] FDG PET/CT. A subgroup of patients with cancer tissue samples at the Institutional Biobank (n = 74/151) was included in the genomic analysis. Features were extracted from both PET and CT images using an in-house tool. The genomic analysis included detection of genetic variants, fusion transcripts, and gene expression. Generalised linear model (GLM) and machine learning (ML) algorithms were used to predict histology and tumour recurrence. RESULTS: Standardised uptake value (SUV) and kurtosis (among the PET and CT radiomic features, respectively), and the expression of TP63, EPHA10, FBN2, and IL1RAP were associated with the histotype. No correlation was found between radiomic features/genomic data and relapse using GLM. The ML approach identified several radiomic/genomic rules to predict the histotype successfully. The ML approach showed a modest ability of PET radiomic features to predict relapse, while it identified a robust gene expression signature able to predict patient relapse correctly. The best-performing ML radiogenomic rule predicting the outcome resulted in an area under the curve (AUC) of 0.87. CONCLUSIONS: Radiogenomic data may provide clinically relevant information in NSCLC patients regarding the histotype, aggressiveness, and progression. Gene expression analysis showed potential new biomarkers and targets valuable for patient management and treatment. The application of ML allows to increase the efficacy of radiogenomic analysis and provides novel insights into cancer biology.