Thoracic Ultrasound as an Alternative to Chest X-ray in Thoracic Surgery Patients: A Single-Center Experience.

Background/Objectives: Chest X-ray (CXR) is currently the most used investigation for clinical follow-up after major noncardiac thoracic surgery. This study explores the use of lung ultrasound (LUS) as an alternative to CXR in the postoperative management of patients who undergo major thoracic procedures. Methods: The patients in our cohort were monitored with both a CXR and a lung ultrasonography after surgery and the day after chest drain removal. The LUS was performed by a member of the medical staff of our unit who was blinded to both the images and the radiologist's report of the CXR. Findings were compared between the two methods. Results: In the immediate postoperative evaluation, 280 patients were compared, finding general agreement between the two procedures at 84% (kappa statistic, 0.603). The LUS showed a sensibility of 84.1%, a specificity of 84.3%, a positive predictive value (PPV) of 60.9%, and a negative predictive value (NPV) of 94.8%. We evaluated 219 out of 280 patients in the postdrainage-removal setting due to technical issues. Concordance between the methods in the postdrainage-removal setting was 89% (kappa statistic, 0.761) with the LUS demonstrating an 82.2% sensibility, a 93.2% specificity, a PPV of 85.7%, and an NPV of 91.3%. Conclusions: The results of this study showed a substantial agreement between LUS and CXR, suggesting that the LUS could reduce the number of X rays in certain conditions. The high NPV allows for the exclusion of PNX and pleural effusion without the need to expose patients to radiation. Discrepancies were noted in cases of mild pneumothorax or modest pleural effusion, without altering the clinical approach.

Tumor inflammatory microenvironment contribution to survival in resected upstaged adenocarcinomas.

INTRODUCTION: Tumor Inflammatory microenvironment (TIME) encompasses several immune pathways modulating cancer development and escape that are not entirely uncoded. The results achieved with immunotherapy elicited the scientific debate on TIME also in non-small cell lung cancer (NSCLC). We aimed to investigate whether TIME (in terms of PD-L1 expression and/or Tumor Infiltrating Lymphocytes - TILs) played a separate role in terms of survival (OS) in resected upstaged lung adenocarcinomas (ADCs), excluding other perioperative variables as confounders. MATERIALS AND METHODS: This retrospective study included 50 patients with a clinically resectable lung ADC, undergoing surgery (lobectomy or segmentectomy) at the Thoracic Unit of Padova University Hospital between 2016 and 2022 and receiving an unexpected pathological upstaging (IIB or higher). RESULTS: Despite microscopical variables increasing from IIB to IIIB, survival was not significantly related to them. OS was better in TIME-active patients (defined as the presence of positive PD-L1 and/or TILs>10 %) than double negatives (PD-L1-/TILs-) (p = 0.01). In IIB or higher ADCs, TIME-active patients showed an improved survival compared to double negatives, merging the current TIME theories. CONCLUSION: TIME seems to be associated with survival independently from other microscopical parameter, even in case of resected upstaged adenocarcinomas.

Is chest tube capnography effective in differentiating between true and false air leaks after minimally invasive thoracic surgery?

OBJECTIVE: Air leak (AL) is the most frequent adverse event after thoracic surgery. When AL occurs, the concentration of the principal gas in the pleural space should be similar to that of air exhaled. Accordingly, we tried to develop a new method to identify AL by analyzing pCO2 levels in the air flow from the chest drainage using capnography. METHODS: This is a prospective observational study of 104 patients who underwent VATS surgery between January 2020 and July 2021. Digital drainage systems were used to detect AL. RESULTS: Eighty-two patients (79%) had lung resection. Among them, 19 had post-operative day 1 air leaks (median 67 ml/min). AL patients had higher intrapleural CO2 levels (median 24 mmHg) (p < 0.001). Median chest drainage duration was 2 days (range 1.0-3.0). Univariable logistic regression showed a linear and significant association between intrapleural CO2 levels and AL risk (OR 1.26, 95% CI 1.17-1.36, p < 0.001, C index: 0.94). The Univariable Gamma model demonstrated that an elevation in CO2 levels was linked to AL on POD1 (with an adjusted mean effect of 7.006, 95% CI 1.59-12.41, p = 0.011) and extended duration of drainage placement (p < 0.001). CONCLUSIONS: Intrapleural CO2 could be an effective tool to assess AL. The linear association between variables allows us to hypothesize the role of CO2 in the identification of AL. Further studies should be performed to identify a CO2 cutoff that will standardize the management of chest drainage.

Pathological complete response in a patient with pleural mesothelioma treated with immunotherapy: a case report.

The role of immunotherapy in the multimodal treatment for pleural mesothelioma (PM) is still under investigation, particularly in the preoperative setting. Pathological complete response (pCR) has been previously described after chemotherapy and immunotherapy; however, there is no prior experience reported with immunotherapy alone before surgery. We report the case of a 58-year-old male with biphasic PM treated with immunotherapy, resulting in a major clinical partial response. Following a multidisciplinary evaluation between thoracic surgeons, medical oncologists, pathologists, radiologists and radiation oncologists, the patient underwent surgery with radical intent through a right extended pleurectomy/decortication (eP/D). Histopathological examination of the specimen confirmed a pathological Complete Response (pCR). This case supports the feasibility and potential efficacy of combining preoperative immunotherapy with surgery in the management of advanced PM.

Survival Outcome After Surgery in Patients With Thymoma Distant Recurrence.

OBJECTIVE: The aim of this study is to describe characteristics and survival outcome of patients who underwent surgical treatment for distant thymoma relapse according to the definition of the International Thymic Malignancy Interest Group. METHODS: Data of patients affected by thymoma recurrence from four different institutions were collected and retrospectively reviewed. Patients with locoregional metastases who underwent nonsurgical therapies and with incomplete data on follow-up were excluded. According to the International Thymic Malignancy Interest Group distant recurrence definition, patients with recurrence due to hematogenic localization were included. Clinical and pathologic characteristics were described using descriptive statistics, whereas survival outcome was calculated using Kaplan-Meier curves and Cox regression analysis. RESULTS: The analysis was conducted on 40 patients. A single localization was present in 13 patients, the relapse was intrathoracic in 28 cases (70%), and lung involvement was found in 26 cases. The liver was operated in seven cases, whereas other kinds of abdominal involvement were detected in eight cases. Adjuvant treatment was administered in 22 cases (55%).Five- and 10-year overall survival (OS) were 67% and 30%, respectively. Univariable analysis identified as significant favorable factor a low-grade histology (A, B1, B2): five-year OS at 92.3% versus 53.3% in high-grade (B3-C) (p = 0.035). Site of recurrence and number of localization did not influence the prognosis, but in patients with adjuvant therapy administration, there was a survival advantage also if not statistically significant: five-year OS 84.8% versus 54.5% in patients without adjuvant therapy (p = 0.101).Multivariable analysis confirmed as independent prognostic factor low-grade histology: hazard ratio = 0.176, 95% confidence interval 0.042-0.744, p = 0.018. CONCLUSIONS: Our study revealed a good survival outcome in patients who underwent surgery for distant thymoma recurrence, independently from the number and site of the relapse localization. Patients with A, B1, or B2 histology presented a significantly better survival than patients with B3-C.

Significance of Spread Through Air Spaces and Vascular Invasion in Early-stage Adenocarcinoma Survival: A Comprehensive Clinicopathologic Study of 427 Patients for Precision Management.

Spread through air spaces (STAS) is a novel invasive pattern of lung cancer associated with poor prognosis in non-small cell cancer (NSCLC). We aimed to investigate the incidence of STAS in a surgical series of adenocarcinomas (ADCs) resected in our thoracic surgery unit and to identify the association of STAS with other clinicopathological characteristics. We retrospectively enrolled patients with stage cT1a-cT2b who underwent resection between 2016 and 2022. For each case, a comprehensive pathologic report was accessible which included histotype, mitoses, pleural invasion, fibrosis, tumor infiltrating lymphocytes, necrosis, inflammation, vascular and perineural invasion, as well as STAS. PD-L1 expression was also investigated. A total of 427 patients with ADCs underwent surgery. Regarding overall survival (OS), no significant difference was observed between the STAS positive (STAS+) and STAS negative (STAS-) groups ( P =0.44). However, vascular invasion (VI) was associated with a poorer survival probability ( P =0.018). STAS+/VI+ patients had tendentially worse survival compared with STAS+/VI- ( P =0.089). ADCs with pathologic evidence of immune system (IS) activation (TILs>10% and PD-L1≥1) demonstrated significantly increased OS compared with ADCs with no IS and VI. In terms of recurrence rate, no statistical differences were found between the STAS+ and STAS- samples ( P =0.2). VI was also linked to a significantly elevated risk of recurrence ( P =0.0048). Our study suggests that in resected early-stage ADCs, STAS+ does not seem to influence recurrence or mortality. VI was instead an adverse pathologic prognostic factor for both survival and recurrence, whereas IS seemed to be protective.

Tracheal Tissue Engineering: Principles and State of the Art.

Patients affected by long-segment tracheal defects or stenoses represent an unsolved surgical issue, since they cannot be treated with the conventional surgery of tracheal resection and consequent anastomosis. Hence, different strategies for tracheal replacement have been proposed (synthetic materials, aortic allografts, transplantation, autologous tissue composites, and tissue engineering), each with advantages and drawbacks. Tracheal tissue engineering, on the other hand, aims at recreating a fully functional tracheal substitute, without the need for the patient to receive lifelong immunosuppression or endotracheal stents. Tissue engineering approaches involve the use of a scaffold, stem cells, and humoral signals. This paper reviews the main aspects of tracheal TE, starting from the choice of the scaffold to the type of stem cells that can be used to seed the scaffold, the methods for their culture and expansion, the issue of graft revascularization at the moment of in vivo implantation, and experimental models of tracheal research. Moreover, a critical insight on the state of the art of tracheal tissue engineering is also presented.

Lung Transplantation in Patients with Previous or Unknown Oncological Disease: Evaluation of Short- and Long-Term Outcomes.

The accurate selection of the recipient is a crucial aspect in the field of lung transplantation (LTX), especially if patients were previously affected by oncological disease. The aim of this bicentric retrospective study was to evaluate short- and long-term outcomes in patients with previous oncological disease or unknown neoplasia found on native lungs submitted to LTX, compared to a control group. A total of 433 patients were included in the analysis, 31 with malignancies (Group 1) and 402 without neoplastic disease (Group 2). The two groups were compared in terms of short- and long-term outcomes. Patients in Group 1 were older (median age 58 years vs. 50 years, p = 0.039) and mostly affected by idiopathic pulmonary fibrosis (55% vs. 40% p = 0.002). Even though in Group 1 a lower rate of late post-operative complications was found (23% vs. 45%, p = 0.018), the median overall survival (OS) was lower compared to the control group (10 months vs. 29 months, p = 0.015). LTX represents a viable therapeutic option for patients with end-stage lung disease and a history of neoplastic disease. However, every case should be carefully debated in a multidisciplinary setting, considering oncological (histology, stage, and proper disease free-interval) and clinical factors (patient's age and comorbidities). A scrupulous post-transplant follow-up is especially mandatory in those cases.

Human tracheal transplantation: A systematic review of case reports.

BACKGROUND: Patients with long-segment airway stenosis not amenable to conventional surgery may benefit from tracheal transplantation. However, this procedure has been only anecdotally reported, and its indications, techniques, and outcomes have not been extensively reviewed. METHODS: We conducted a systematic Literature search to identify all original articles reporting attempts at tracheal transplantation in humans. RESULTS: Of 699 articles found by the initial search, 11 were included in the systematic review, describing 14 cases of tracheal transplantation. Patients underwent transplantation for benign stenosis in nine cases, and for malignancies in five cases. In 12 cases blood supply to the trachea was provided by wrapping the graft in a vascularized recipient's tissue, while in 2 cases the trachea was directly transplanted as a vascularized composite allograft. The transplantation procedure was aborted before orthotopic transplantation in two patients. Among the remaining 12 patients, there was 1 operative mortality, while 4 patients experienced complications. Immunosuppressants drugs were administered to the majority of patients postoperatively, and only one group of authors attempted their withdrawal, in five patients. At the end of follow-up, all 11 patients surviving the operation were alive, but 2 had a recurrent tracheal stenosis requiring an airway appliance for breathing. CONCLUSION: Human tracheal transplantation is still at an embryonic phase. Studies available in the Literature report different surgical techniques, and information on long-term outcomes is still limited. Future research is needed in order to understand the clinical value of this procedure.

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

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

Surgery for tracheal and laryngotracheal stenosis: a historical case series.

OBJECTIVES: Benign (laryngo-)tracheal stenosis is a relatively rare pathology and its surgical treatment is performed only at few specialized centres. This study aims to investigate outcomes after (laryngo-)tracheal resection-anastomosis, to explore potential risk factors for postoperative complications and to assess whether, over a 33-year period, there were major changes in surgical indications, techniques or outcomes. METHODS: Retrospective, single-centre review of all consecutive patients who underwent tracheal or laryngo-tracheal resection/anastomosis for benign pathologies from 1990 to 2023. RESULTS: Overall, 211 patients underwent tracheal (149 patients, 70.6%) and laryngo-tracheal (62 patients, 29.4%) resection-anastomosis. Of these, 195 patients (93.8%) were affected by iatrogenic stenosis, while 13 (6.2%) suffered from idiopathic stenosis. The median length of stenosis was 25 mm (interquartile range 1-3, 20-30). The overall morbidity rate was 27.5%, while major morbidity occurred in 10.5% of cases. One patient (0.5%) died in the postoperative period. Glottic oedema (17 patients, 8.1%), granulations (12 patients, 5.7%) and restenosis (10 patients, 4.7%) were the main complications. The only independent risk factor for postoperative complications was the length of the resected airway (P = 0.019). In the latest half of the study period, an older median age was observed, and no patient with idiopathic tracheal stenosis underwent surgery. Postoperative outcomes were comparable between surgical eras. CONCLUSIONS: Surgical treatment of (laryngo-)tracheal stenosis is challenging and should be performed by specialized centres. In our experience, morbidity and mortality rates were satisfactory, and in most cases, patients could breathe without tracheostomy. The length of the stenosis was the most significant risk factor for postoperative complications.

An alternative surgical access for posterior tracheal defects or fistulae situated between the cervical and thoracic region.

Posterior tracheal lesion defects between the cervical and the thoracic region represent a surgical challenge. Cervicotomy or median sternotomy might not allow a satisfactory exposure of the defect, and a history of prior neck surgeries could further complicate the procedure. We propose a high posterior right thoracotomic approach, by which the entire posterior aspect of the trachea is visible, up to the cervical region. We describe our experience with this approach, which is best suited for cases where a non-circumferential repair of the trachea is attempted.

Three-Dimensional Imaging-Guided Lung Anatomic Segmentectomy: A Single-Center Preliminary Experiment.

Background and objectives: VATS segmentectomy has been proven to be effective in the treatment of stage I NSCLC, but its technical complexity remains one of the most challenging aspects for thoracic surgeons. Furthermore, 3D-CT reconstruction images can help in planning and performing surgical procedures. In this paper, we present our personal experience of 11 VATS anatomical resections performed after accurate pre-operative planning with 3D reconstructions. Materials and methods: A 3D virtual model of the lungs, airways, and vasculature was obtained, starting from a 1.25 mm 3-phase contrast CT scan, and the original images were used for the semi-automatic segmentation of the lung parenchyma, airways, and tumor. Results: Six males and five females were included in this study. The median diameter of the pulmonary lesion at the pre-operative chest CT scan was 20 mm. The surgical indication was confirmed in seven patients: in three cases, a lobectomy, instead of a segmentectomy, was needed due to intraoperative findings of nodal metastasis. Meanwhile, only in one case, we performed a lobectomy because of inadequate surgical resection margins. Skin-to-skin operative average time was 142 (IQR 1-3 105-182.5) min. The median post-operative stay was 6 (IQR 1-3 3.5-7) days. The mean value of the closest surgical margin was 13.7 mm. Conclusion: Image-guided reconstructions are a useful tool for surgeons to perform complex resections in order to spare healthy parenchyma and to ensure disease-free margins. Nevertheless, human skill and surgeon experience still remain fundamental for the final decisions regarding the proper resection to perform.

Perioperative outcomes in redo VATS for pulmonary ipsilateral malignancy: A single center experience.

BACKGROUND: The role of video-assisted thoracoscopic surgery for oncological major pulmonary resections is now well established; however, the literature within pulmonary re-operations is still limited. The purpose of this study is to evaluate the safety and efficacy of redo thoracoscopic resections for ipsilateral pulmonary malignancy. METHODS: Data from patients undergoing video-assisted thoracoscopic surgery at the Unit of Thoracic Surgery of Padua were analyzed, comparing the results between the first and second ipsilateral surgery. The retrospective study included patients who underwent 2 thoracoscopic surgeries for oncological reasons between 2015 and 2022. The variables considered included patients' baseline characteristics, pre, intra, and postoperative data. RESULTS: The study enrolled 51 patients undergoing ipsilateral thoracoscopic re-operation. The statistical analysis showed that surgical time (95min vs 115min; p = 0.009), the presence of intrapleural adhesions at second surgery (30 % vs 76 %; p < 0.001), overall pleural fluid output (200 vs 560 ml; p = 0.003), time with pleural drainage (2 vs 3 days; p = 0.027), air leaks duration time (p = 0.004) and post-operative day of discharge (3 vs 4 days; p = 0.043) were significantly higher in the re-operation group. No statistical differences were observed between the 2 groups respect to R0 resection rate (90.2 % vs 89.1 %; p=>0.9) and complications (5.8 % vs 15.6 %; p = 0.11). The conversion rate to open surgery was 11.8 %. CONCLUSION: Although some differences emerged between the first and second intervention, they had minimal impact on the clinical course of the patients. Therefore, thoracoscopic surgery has been shown to be safe and effective in re-operations with satisfying perioperative outcomes. To achieve such results, these procedures should be reserved for experienced surgeons.

Microscopical Variables and Tumor Inflammatory Microenvironment Do Not Modify Survival or Recurrence in Stage I-IIA Lung Adenocarcinomas.

Microscopical predictors and Tumor Immune Microenvironment (TIME) have been studied less in early-stage NSCLC due to the curative intent of resection and the satisfactory survival rate achievable. Despite this, the emerging literature enforces the role of the immune system and microscopical predictors as prognostic variables in NSCLC and in adenocarcinomas (ADCs) as well. Here, we investigated whether cancer-related microscopical variables and TIME influence survival and recurrence in I-IIA ADCs. We retrospectively collected I-IIA ADCs treated (lobectomy or segmentectomy) at the University Hospital (Padova) between 2016 and 2022. We assigned to pathological variables a cumulative pathological score (PS) resulting as the sum of them. TIME was investigated as tumor-infiltrating lymphocytes (TILs < 11% or ≥11%) and PD-L1 considering its expression (<1% or ≥1%). Then, we compared survival and recurrence according to PS, histology, TILs and PD-L1. A total of 358 I-IIA ADCs met the inclusion criteria. The median PS grew from IA1 to IIA, indicating an increasing microscopical cancer activity. Except for the T-SUVmax, any pathological predictor seemed to be different between PD-L1 < 1% and ≥1%. Histology, PS, TILs and PD-L1 were unable to indicate a survival difference according to the Log-rank test (p = 0.37, p = 0.25, p = 0.41 and p = 0.23). Even the recurrence was non-significant (p = 0.90, p = 0.62, p = 0.97, p = 0.74). According to our findings, resection remains the best upfront treatment in I-IIA ADCs. Microscopical cancer activity grows from IA1 to IIA tumors, but it does not affect outcomes. These outcomes are also unmodified by TIME. Probably, microscopical cancer development and immune reaction against cancer are overwhelmed by an adequate R0-N0 resection.

Radiomics of spinal muscles: toward a radiological biomarker for allograft rejection in lung transplant.

PURPOSE: To assess the role of muscle composition and radiomics in predicting allograft rejection in lung transplant. MATERIAL AND METHODS: The last available HRCT before surgery of lung transplant candidates referring to our tertiary center from January 2010 to February 2020 was retrospectively examined. Only scans with B30 kernel reconstructions and 1 mm slice thickness were included. One radiologist segmented the spinal muscles of each patient at the level of the 11th dorsal vertebra by an open-source software. The same software was used to extract Hu values and 72 radiomic features of first and second order. Factor analysis was applied to select highly correlating features and then their prognostic value for allograft rejection was investigated by logistic regression analysis (level of significance p < 0.05). In case of significant results, the diagnostic value of the model was computed by ROC curves. RESULTS: Overall 200 patients had a HRCT prior to the transplant but only 97 matched the inclusion criteria (29 women; mean age 50.4 ± 13 years old). Twenty-one patients showed allograft rejection. The following features were selected by the factor analysis: cluster prominence, Imc2, gray level non-uniformity normalized, median, kurtosis, gray level non-uniformity, and inverse variance. The radiomic-based model including also Hu demonstrated that only the feature Imc2 acts as a predictor of allograft rejection (p = 0.021). The model showed 76.6% accuracy and the Imc2 value of 0.19 demonstrated 81% sensitivity and 64.5% specificity in predicting lung transplant rejection. CONCLUSION: The radiomic feature Imc2 demonstrated to be a predictor of allograft rejection in lung transplant.

Laser-assisted lung metastasectomy: a systematic review.

Laser-assisted resection (LAR) of pulmonary metastases offers several potential advantages compared to conventional surgical techniques. However, the technical details, indications and outcomes of LAR have not been extensively reviewed. We conducted a systematic literature search to identify all original articles reporting on LAR of pulmonary metastases. All relevant outcomes, including morbidity rate, R0 rate, pulmonary function tests, overall- (OS) and relapse-free survival (RFS) rates were collected. Additionally, a comparison between outcomes obtained by laser-assisted and conventional resection techniques was provided. Of 2629 articles found by the initial search, 12 were selected for the systematic review. Following LAR, the R0 rate ranged between 72 and 100% and the morbidity rate ranged from 0 to 27.5%. The postoperative decline in forced expiratory volume in 1 s varied between 3.4 and 11%. Median OS and RFS were 42-77.6 months and 9-34.1 months, respectively. Compared with patients treated by other resection techniques, patients treated by LAR frequently had a higher number of metastases and a higher rate of bilateral disease. Despite this, no significant differences were observed in R0 rate, morbidity rate, and median OS rate, while only 1 study found a lower RFS rate in the LAR cohort. Although selection bias limits the comparability of outcomes, the findings of this review suggest that LAR is a valid alternative to conventional procedures of lung metastasectomy. The main difficulties of this technique consist in the adoption of a video-assisted thoracoscopic approach, and in the pathologic assessment of resection margins.

Intrathymic Localization of Melanoma: A Brief Report of Two Cases and a Review of the Literature.

Intrathymic localizations of melanoma represent a very rare entity, with fewer than ten cases of intrathymic melanoma described in the literature. Herein, we describe two cases of patients who underwent surgical removal of a thymic mass at our thoracic surgery department between 2015 and 2022. The final pathological examination revealed a malignant melanoma in both cases; we therefore carried out a literature review to identify such rare and similar cases. In the first case, the intrathymic localization of melanoma was the first manifestation of the disease, posing a dilemma regarding the metastatic and primitive nature of the neoplasm. The second case described a thymic metastasis from a known previous cutaneous melanoma, for which the patient had successfully been treated six years earlier. After carefully reviewing the literature, we identified only six cases of verified primary intrathymic melanomas and one case of intrathymic metastasis resulting from melanoma previously described. Pathologists should be aware of the occurrence of this rare entity and mindful of the differential diagnoses. Several tools, including immunostaining of melanocytic markers and molecular investigations, are mandatory for final pathological diagnosis.

Upfront surgery for N2 NSCLC: a large retrospective multicenter cohort study.

BACKGROUND: The optimal sequence and combination of surgery, chemotherapy and radiotherapy in patients with N2 non-small cell lung cancer (NSCLC) remain undefined. The aim of our study was to compare two treatment options for N2 NSCLC-induction therapy with subsequent surgery versus upfront surgery with adjuvant treatment. METHODS: We retrospectively reviewed 405 patients with N2 disease in two centers, between January 2010 and December 2016. They were divided into two groups: the Induction Group, composed of patients who received neoadjuvant chemotherapy, and the Upfront surgery Group, composed of patients who underwent surgery as first-line therapy. Propensity score-matched (PSM) analysis was performed, and 52 patients were included in each group. Primary endpoints were: recurrence, overall survival (OS) and disease-free survival (DFS). RESULTS: After the PSM, no differences were observed in general characteristics, perioperative results, rates and severity of complications, and histopathology results. Seventeen patients (32.7%) of the induction group and 21 (40.4%) of the upfront surgery group had mediastinal lymph nodal involvement with skipping (p = 0.415). Recurrence rate was not different between the two groups (57.7% vs 50.0%, p = 0.478). No differences were observed in terms of OS (40.98 ± 35.78 vs 37.0 ± 40.69 months, p = 0.246) and DFS (29.67 ± 36.01 vs 27.96 ± 40.08 months, p = 0.697). The multivariable analysis identified the pT stage and skipping lymph node metastasis as independent predictive factors for OS. CONCLUSIONS: Upfront surgery followed by adjuvant therapy does not appear inferior in terms of recurrence, OS and DFS, compared to induction chemotherapy with subsequent surgery.