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.

Robotic thymectomy in thymic tumors: a multicenter, nation-wide study.

OBJECTIVES: Robotic thymectomy has been suggested and considered technically feasible for thymic tumors. 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 multicenter study sought to evaluate the early and long-term outcomes after robot-assisted thoracoscopic thymectomy in thymic epithelial tumors. METHODS: All patients with thymic epithelial tumors operated through a robotic thoracoscopic approach between 2002 and 2022 from 15 Italian centers 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. Median diameter of tumor resected was 4cm (interquartile range 3-5.5cm), 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 tumor-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 tumors we demonstrated that robot-enhanced thoracoscopic thymectomy is a technically sound and safe procedure with a low complication rate and optimal oncological outcomes.

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.

Alteration of the immunophenotype and cytokine profiles in patients affected by neuroendocrine neoplasms.

PURPOSE: Neuroendocrine neoplasms (NENs) are tumors that arise from cells of the endocrine system and are most common in the gastrointestinal tract, the pancreas, and the lungs. Their incidence is rapidly increasing and the therapeutic options available are limited. METHODS: Since the immune system can interfere with tumor growth and response to therapy, using flow cytometry we investigated the immunophenotype in samples of peripheral blood leukocytes from patients with pancreatic (Pan-NENs) and pulmonary NENs (Lung-NENs). Moreover, we performed a multiplex analysis of 13 key cytokines and growth factors essential for the immune response in the plasma of NEN patients and controls. RESULTS: Patients presented with a higher percentage of granulocytes, a lower percentage of lymphocytes, and an increase in the granulocytes to lymphocytes ratio compared to healthy donors. These alterations were more marked in patients with metastasis. Somatostatin analogs (SSAs) restored the immunophenotype of patients to that seen in healthy donors. Finally, Pan-NEN patients showed a higher plasma concentration of IP-10, MCP-1, and IL-8 compared to healthy donors, suggesting a potential role for these cytokines as diagnostic biomarkers. CONCLUSION: This study highlighted differences in the immunophenotype of patients with Pan- and Lung-NENs compared to healthy individuals; these alterations were partially restored by therapy.

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.

Radioisotope-Guided Excision of Mediastinal Lymph Nodes in Patients with Non-Small Cell Lung Carcinoma: Feasibility and Clinical Impact.

BACKGROUND: Intraoperative localisation of nodal disease in non-small cell lung cancer (NSCLC) can be challenging. Lymph node localisation via radiopharmaceuticals is used in many conditions; we tested the feasibility of this approach in NSCLC. METHODS: NSCLC patients were prospectively recruited. Intraoperative peri-tumoral injections of [99mTc]Tc-albumin nanocolloids were performed, followed by removing the tumour and locoregional lymph nodes. These were examined ex vivo with a gamma probe and labelled sentinel lymph nodes (SLNs) if they showed any activity or non-sentinel lymph nodes (nSLNs) if they did not. Thereafter, the surgical field was scanned with the probe; any further radioactive lymph node was removed and labelled as "extra" SLNs (eSLNs). All specimens were sent to histology, and metastatic status was recorded. RESULTS: 48 patients were enrolled, and 290 nodal stations were identified: 179 SLNs, 87 nSLNs, and 24 eSLNs. A total of 44 nodal metastases were identified in 22 patients, with 36 of them (82%) located within SLNs. Patients with nSLNs metastases had at least a co-existing positive SLN. No metastases were found in eSLNs. CONCLUSIONS: The technique shows high sensitivity for intraoperative nodal metastases identification. This information could allow selective lymphadenectomies in low-risk patients or more aggressive approaches in high-risk patients.

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.

The Overweight Paradox: Impact of Body Mass Index on Patients Undergoing VATS Lobectomy or Segmentectomy.

The aim of this study was to assess the impact of BMI on perioperative outcomes in patients undergoing VATS lobectomy or segmentectomy. Data from 5088 patients undergoing VATS lobectomy or segmentectomy, included in the VATS Group Italian Registry, were collected. BMI (kg/m2) was categorized according to the WHO classes: underweight, normal, overweight, obese. The effects of BMI on outcomes (complications, 30-days mortality, DFS and OS) were evaluated with a linear regression model, and with a logistic regression model for binary endpoints. In overweight and obese patients, operative time increased with BMI value. Operating room time increased by 5.54 minutes (S.E. = 1.57) in overweight patients, and 33.12 minutes (S.E. = 10.26) in obese patients (P < 0.001). Compared to the other BMI classes, overweight patients were at the lowest risk of pulmonary, acute cardiac, surgical, major, and overall postoperative complications. In the overweight range, a BMI increase from 25 to 29.9 did not significantly affect the length of stay, nor the risk of any complications, except for renal complications (OR: 1.55; 95% CI: 1.07-2.24; P = 0.03), and it reduced the risk of prolonged air leak (OR: 0.8; 95% CI: 0.71-0.90; P < 0.001). 30-days mortality is higher in the underweight group compared to the others. We did not find any significant difference in DFS and OS. According to our results, obesity increases operating room time for VATS major lung resection. Overweight patients are at the lowest risk of pulmonary, acute cardiac, surgical, major, and overall postoperative complications following VATS resections. The risk of most postoperative complications progressively increases as the BMI deviates from the point at the lowest risk, towards both extremes of BMI values. Thirty days mortality is higher in the underweight group, with no differences in DFS and OS.

Incidence of Tracheal Stenosis in ICU Hospitalized COVID-19 Patients: Results from a Prospective, Observational, Multicenter Study.

Background: Tracheal stenosis represents a fearsome complication that substantially impairs quality of life. The recent SARS-CoV-2 pandemic increased the number of patients requiring invasive ventilation through prolonged intubation or tracheostomy, increasing the risk of tracheal stenosis. Study design and methods: In this prospective, observational, multicenter study performed in Lombardy (Italy), we have exanimated 281 patients who underwent prolonged intubation (more than 7 days) or tracheostomy for severe COVID-19. Patients underwent CT scan and spirometry 2 months after hospital discharge and a subsequent clinical follow-up after an additional 6 months (overall 8 months of follow-up duration) to detect any tracheal lumen reduction above 1%. The last follow-up evaluation was completed on 31 August 2022. Results: In the study period, 24 patients (8.5%, CI 5.6-12.4) developed tracheal stenosis in a median time of 112 days and within a period of 200 days from intubation. Compared to patients without tracheal stenosis, tracheostomy was performed more frequently in patients that developed stenosis (75% vs 54%, p = 0.034). Tracheostomy and alcohol consumption (1 unit of alcohol per day) increased risk of developing tracheal stenosis of 2.6-fold (p = 0.047; IC 0.99-6.8) and 5.4-fold (p = 0.002; CI 1.9-16), respectively. Conclusions: In a large cohort of patients, the incidence of tracheal stenosis increased during pandemic, probably related to the increased use of prolonged intubation. Patients with histories of prolonged intubation should be monitored for at least 200 days from invasive ventilation in order to detect tracheal stenosis at early stage. Alcohol use and tracheostomy are risk factors for developing tracheal stenosis.

Extracorporeal membrane oxygenation support in oncological thoracic surgery.

The use of extracorporeal lung support (ECLS) during thoracic surgery is a recent concept that has been gaining increasing approval. Firstly introduced for lung transplantation, this technique is now increasingly adopted also in oncological thoracic surgical procedures. In this review, we focus on the cutting-edge application of extracorporeal membrane oxygenation (ECMO) during oncological thoracic surgery. Therefore, we report the most common surgical procedures in oncological thoracic surgery that can benefit from the use of ECMO. They will be classified and discussed according to the aim of ECMO application. In particular, the use of ECMO is usually limited to certain lung surgery procedures that can be resumed such as in procedures in which an adequate ventilation is not possible such as in single lung patients, procedures where conventional ventilation can cause conflict with the surgical field such as tracheal or carinal surgery, and conventional procedures requiring both ventilators and hemodynamic support. So far, all available evidence comes from centers with large experience in ECMO and major thoracic surgery procedures.

Air leak and intraoperative bleeding in thoracic surgery: a Delphi consensus among the members of Italian society of thoracic surgery.

Background: Persistent air leak and the management of intraoperative blood loss are common threats in thoracic surgical practice. The availability of new procedures, technology and materials is constantly evolving topical hemostats and surgical sealants must be added to this toolkit. Topical hemostats and surgical sealants differ according to their chemical nature and physical characteristics, to their origin and mechanism of action, regulatory/registration and vigilance paths. A Delphi consensus was set to highlight the different points of view on the use of topical haemostatic products and sealants among the members of Italian Society of thoracic surgery. Methods: The board was formed by a group of five Italian experts; in the first phase after a careful review of the scientific literature and two rounds, the board finally generated 16 consensus statements for testing across a wider audience. During the second phase, the statements were collated into a questionnaire, which was electronically sent to a panel of 46 Italian surgeons, experts in the field. Results: Out of 46 Italian surgeons, 33 (72%) panel members responded to the Delphi questionnaire. All the items reached a positive consensus, with elevated levels of agreement, as demonstrated by the presence of a 100% consensus for nine items. For the remaining 7 statements the minimum level of consent was 88% (29 participants approved the statement and 4 disagreed) and the maximum was 97% (32 participants approved the statement and 1 was in disagreement). Conclusions: The present Delphi analysis shows that air leak and intraoperative bleeding are clinical problems well known among thoracic surgeons. Nevertheless, the aim of the scientific societies and of the group of experts is to execute the education activities in the surgery community. This Delphi survey suggest the need of wider and updated scientific information about technical and registration characteristics of most recent technologic solutions, such as the of topical hemostats and surgical sealants to provide healthcare and administrative staff with the opportunity to work and interact through a common and shared language and eventually to guarantee minimal requirements of assistance.

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).

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.

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.

Lung Metastases: Current Surgical Indications and New Perspectives.

Pulmonary metastasectomy is an established treatment that can provide improved long- term survival for patients with metastatic tumor(s) in the lung. In this mini-review, we discuss the state of the art of thoracic surgery in surgical management of lung metastases which actually occurs for a large part of surgical activity in thoracic surgery department. We describe the principles of surgical therapy that have been defined across the time, and that should remain the milestones of lung metastases treatment: a radical surgery and an adequate lymphadenectomy. We then focus on current surgical indications and report the oncological results according to the surgical approach (open vs. mini-invasive), the histological type and number of lung metastases, and in case of re-metastasectomy. Finally, we conclude with a brief overview about the future perspectives in thoracic surgery in treatment of lung metastases.