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Background: In stage III to IVa thymic epithelial tumors (TETs), infiltration of the superior vena cava (SVC) is not rare. The extent of SVC resection depends on the width of the area of neoplastic invasion. Our article aims to evaluate the safety and long-term outcomes of extended thymectomy for TETs with SVC resection compared with advanced-stage TETs patients without SVC resection., Methods: Retrospective review of the experience on patients who underwent extended thymectomy for TETs in the last 20 years, according to STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) methodology. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. A backward stepwise Cox regression multivariate analysis was performed to determine factors associated with long-term outcomes., Results: A total of 78 patients underwent surgery for advanced-stage TETs (Masaoka-Koga stages III-IVa) from January 1998 to April 2019. Fourteen (17.9%) underwent thymectomy with resection of SVC. Presence of a thymic carcinoma (hazard ratio , 2.26; 95% confidence interval, 1.82-6.18; P = .038) and the SVC resection (hazard ratio, 1.89; 95% confidence interval, 1.11-3.96; P = .041) were adverse prognostic factors at multivariate analysis. The median OS and the PFS of all SVC resected patients were 50 (range, 5-207) months and 31 (range, 5-151) months, respectively. There was no significant difference in OS (P = .28) and PFS (P = .32) between SVC-resected and non-SVC-resected patients., Conclusions: SVC resection is a safe and effective procedure to restore the venous system continuity and does not seem to affect survival and disease recurrence. This surgical approach allows radical resection of locally advanced TETs, even after neoadjuvant chemotherapy., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Lung ischemia/reperfusion (IR) injury contributes to the development of severe complications in patients undergoing transplantation. Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) exert beneficial actions comparable to those of MSCs without the risks of the cell-based strategy. This research investigated EV effects during IR injury in isolated rat lungs., Methods: An established model of 180-minutes ex vivo lung perfusion (EVLP) was used. At 60 minutes EVs (n = 5) or saline (n = 5) were administered. Parallel experiments used labeled EVs to determine EV biodistribution (n = 4). Perfusate samples were collected to perform gas analysis and to assess the concentration of nitric oxide (NO), hyaluronan (HA), inflammatory mediators, and leukocytes. Lung biopsies were taken at 180 minutes to evaluate HA, adenosine triphosphate (ATP), gene expression, and histology., Results: Compared with untreated lungs, EV-treated organs showed decreased vascular resistance and a rise of perfusate NO metabolites. EVs prevented the reduction in pulmonary ATP caused by IR. Increased medium-high-molecular-weight HA was detected in the perfusate and in the lung tissue of the IR + EV group. Significant differences in cell count on perfusate and tissue samples, together with induction of transcription and synthesis of chemokines, suggested EV-dependent modulation of leukocyte recruitment. EVs upregulated genes involved in the resolution of inflammation and oxidative stress. Biodistribution analysis showed that EVs were retained in the lung tissue and internalized within pulmonary cells., Conclusions: This study shows multiple novel EV influences on pulmonary energetics, tissue integrity, and gene expression during IR. The use of cell-free therapies during EVLP could constitute a valuable strategy for reconditioning and repair of injured lungs before transplantation., (Copyright © 2019 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Owing to the expected poor long-term outcomes and high postoperative morbidity and mortality, patients with stage IIIA-N2 tumors candidate to pneumonectomy (PN) are usually excluded from surgery. This study aims to analyze the outcome of patients who underwent PN to prove its safety and feasibility., Patients and Methods: We retrospectively analyzed data from 233 patients who underwent PN for N2 non-small-cell lung cancer (NSCLC) between 1998 and 2015. Eighty-five patients were occult N2 disease (group 1), whereas 148 patients underwent induction therapy (IT) for stage IIIA-N2 (group 2)., Results: Overall morbidity, postoperative mortality, and 90-day mortality rates were 46.8%, 2.6%, and 8.6%, respectively. The 2 groups (group 1 vs. 2) had similar postoperative and 90-day mortality rates: 2.4% versus 2.7% (P = 1.00), and 9.4% versus 8.1% (P = .81), respectively. The incidence of major morbidity was higher and statistically significant in group 2 compared with group 1: 23% versus 12.9% (P = .1). Postoperative bronchopleural fistula occurred in 4.7% (4/85) of patients with occult N2 (group 1) and in 10.1% (15/148) of patients undergoing IT (group 2) (P = .10). Median overall survival (OS) was 2.2 years, with a 3 and 5-year OS of 43.4% and 31.6%, respectively. Disease-free survival (DFS) was 1.5 years, with 3 and 5-year DFS of 41.6% and 32%, respectively; no difference in OS and DFS between the 2 groups was found., Conclusions: Considering the acceptable morbidity and mortality rate and the long-term survival, PN should not be excluded for selected patients with stage IIIA-N2 NSCLC as a matter of principle., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The role of extended pulmonary resection for lung metastases is still unclear, and little information is available in the literature. This study was performed to analyze the outcomes and prognostic factors of patients who underwent extended resections for pulmonary metastases., Methods: From 1998 to 2013, 1027 patients underwent lung metastasectomy procedures. Twenty-nine patients had extended pulmonary resections: three resections of the chest wall, one azygos, one diaphragm, four vascular resections/reconstructions, six sleeve resections, and 14 pneumonectomies., Results: Extended resection was performed for metastatic disease mainly from epithelial (62.1%) and sarcomatous (20.7%) tumors. Complete resection was obtained in all patients. Thirty-day operative morbidity and mortality rates were 38% (11 of 29) and 0%, respectively. Only one patient had a major complication due to a bronchopleural fistula. Mean hospital stay was 6.3 days. After a median follow-up of 27 months, 16 patients (55%) had died. At univariate analysis, survival was determined by primary tumor histology (p = 0.03); the number of metastases, nodal status, disease-free interval or extension of surgery (pneumonectomy vs. lobar resection) were not related to survival probably due to the low number of patients. Overall survival after a complete extended metastasectomy was 66% at 2 years, 42% at 5 years, and 36% at 10 years., Conclusions: Extended resections performed during pulmonary metastasectomies are associated with low mortality and morbidity rates and an acceptable long-term survival when performed in selected patients susceptible to complete resection.

Background: This study assessed perioperative outcome and long-term survival in a large series of patients with malignant pleural mesothelioma who underwent extrapleural pneumonectomy (EPP) to identify prognostic factors allowing better patient selection., Methods: We retrospectively collected data from nine referral centers for thoracic surgery in Italy. Perioperative outcome and survival data were available for 518 malignant pleural mesothelioma patients (84.4% with epithelial tumors, 68.0% with pathologic stage 3 disease) who underwent EPP with intention-to-treat (R0/R1) between 2000 and 2010. Induction chemotherapy was administered in 271 patients (52.3%) and adjuvant therapy in 373 patients (72.0%), including radiotherapy in 213 patients (41.1%), adjuvant chemotherapy in 43 patients (8.3%), and both in 117 patients (22.6%)., Results: In all, 136 patients (26.3%) had major complications after EPP, and 36 (6.9%) died within 90 days after surgery. The median overall survival was 18 months, with a 1-, 2-, and 3-year overall survival of 65%, 41%, and 27%, respectively. At multivariable analysis adjusted for age and disease stage, male sex (hazard ratio [HR] 1.47, 95% confidence interval [CI]: 1.12 to 1.92), nonepithelial histology (HR 1.96, 95% CI: 1.48 to 2.58), and trimodality treatment using induction chemotherapy (HR 0.61, 95% CI: 0.43 to 0.85) were significantly associated with survival. Development of a major complication also significantly worsened outcome (HR 1.85, 95% CI: 1.37 to 2.50)., Conclusions: The success of EPP in the context of a multimodality treatment depends on a series of patient characteristics. Female patients, patients with epithelial tumors, and patients who received induction chemotherapy will best benefit from EPP., (Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: During the period that randomized clinical trials were establishing the role of adjuvant therapy in tumors larger than 5 cm without lymph-node invasion, which shifted from stage IB (6th TNM) to stage II (7th TNM), we derived the rate of shifted patients in our series and analyzed the relationship between specific patient- and tumor- characteristics, and clinical outcome, to identify putative prognostic factors., Methods: We retrospectively collected data (age, sex, smoking status, type of surgery grading, and histological type) from 467 patients who underwent radical surgery for primary 6th TNM-T2N0 non-small cell lung cancer patients between 1998 and 2009 at our institute. Categorical variables were cross-tabulated by tumor staging according to the 7th TNM edition, and they were tested both for association with stage and survival., Results: One hundred and eighteen patients shifted to stage II, mainly older patients and patients with a sarcomatoid or a poorly differentiated carcinoma. Median overall survival time was significantly different across stages. Among the factors investigated, only the tumor dimension resulted in being statistically significant in multivariate analysis., Conclusions: Nearly a quarter of patients shifted from stage I (6th TNM) to stage II (7th TNM), raising a major need for information on the effects of adjuvant chemotherapy in this group of patients. Our findings suggest that randomized clinical trials aimed at addressing this topic should consider only tumor dimensions as principal selection criteria.

Background: Bilobectomy for lung cancer is considered a high-risk procedure for the increased postoperative complication rate and the negative impact on survival. We analyzed the safety and the oncologic results of this procedure., Methods: We retrospectively reviewed patients who underwent bilobectomy for lung cancer between October 1998 and August 2009. Age, gender, bilobectomy type and indication, complications, pathology, stage, and survival were analyzed., Results: Bilobectomy was performed on 146 patients (101 men; mean age, 62 years). There were 77 upper-middle and 69 middle-lower bilobectomies. Indications were tumor extending across the fissure in 27 (18.5%) patients, endobronchial tumor in 39 (26.7%), extrinsic tumor or nodal invasion of bronchus intermedius in 66 (45.2%), and vascular invasion in 14 (9.6%). An extended resection was performed in 24 patients (16.4%). Induction therapy was performed in 43 patients (29.4%). Thirty-day mortality was 1.4% (n=2). Overall morbidity was 47.2%. Mean chest tube persistence was 7 days (range, 6 to 46 days). Overall 5-year survival was 58%. Significance differences in survival were observed among different stages (stage I, 70%; stage II, 55%; stage III, 40%; p=0.0003) and the N status (N0, 69%; N1, 56%; N2, 40%; p=0.0005). Extended procedure (p=0.0003) and superior bilobectomy (p=0.0008) adversely influenced survival. Multivariate analysis demonstrated that an extended resection (p=0.01), an advanced N disease (p=0.02), and an upper-mild lobectomy (p=0.02) adversely affected prognosis., Conclusions: Bilobectomy is associated with a low mortality and an increased morbidity. Survival relates to disease stage and N factor. Optimal prognosis is obtained in patients with lower-middle lobectomy without extension of the resection., (Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Introduction: The International Registry of Lung Metastases defined a new staging system based on identified prognostic factors for long-term survival after metastasectomy. The aim of our study was to confirm the validity of the International Registry of Lung Metastases classification system in patients who underwent curative lung metastasectomy in a single center., Methods: We retrospectively reviewed 575 patients who underwent 708 lung metastasectomies from January 1998 to October 2008. Complete curative pulmonary resections were performed in 490 cases (85%). Three hundred seventy-two patients developed lung metastases from epithelial tumors, 80 from sarcomas, 27 from melanomas, and 11 from germ cell tumors. The mean disease-free interval (DFI) was 46.6 months. Open surgical resection was performed in 479 patients. One hundred eighty-five patients had a single-lung metastasis. Lymph node dissection was performed in 353 cases., Results: After a mean follow-up of 34 months, 247 patients (43%) had died. Multivariate analysis disclosed that completeness of resection (p < 0.0001), patients with germ cell tumors (p = 0.04), and DFI ≥36 months (p = 0.01) were also associated with a better prognosis. The actuarial survival after complete metastasectomy was 74% at 2 years and 46% at 5 years., Conclusions: We confirmed completeness of surgery, histology, and DFI ≥36 months as independent prognostic factors. Number of metastases, presence of lymph node metastases, surgical approach, and number of metastasectomies did not statistically influence long-term survival.

Background: To address whether systematic lymph node dissection is always necessary in early lung cancer, we identified factors predicting nodal involvement in a screening series and applied them to nonscreening-detected cancers., Methods: In the 97 patients with clinical T1-2N0M0 lung cancer (<3 cm), enrolled in the Continuous Observation of Smoking Subjects computed tomography (CT) screening study, who underwent curative resection with radical mediastinal lymph node dissection, we examined factors associated with hilar extrapulmonary and mediastinal nodal involvement. Nodule size plus positive/negative positron emission tomography (PET)-CT (usually as maximum standard uptake value [maxSUV]) were subsequently evaluated retrospectively for their ability to predict nodal involvement in 193 consecutive patients with nonscreening-detected clinical stage I lung cancer., Results: Among Continuous Observation of Smoking Subjects patients, 91 (94%) were pN0, and six (6.2%) were pN+. All patients with maxSUV <2.0 (p = 0.08) or pathological nodule ≤10 mm (p = 0.027) were pN0 (62 cases). Nodal metastases occurred in 6 cases among the 29 (17%) patients with lung nodule >10 mm and maxSUV ≥2.0 (p = 0.002 versus the other 62 cases). In the nonscreening series, 42 of 43 cases with negative PET-CT (usually maxSUV <2.0) or nodule ≤10 mm were pN0; 33 of 149 (22%) cases with positive PET-CT (usually maxSUV ≥ 2.0) and nodule >10 mm were pN+ (p = 0.001 versus the 43 cases)., Conclusions: This limited experience suggests that in early-stage clinically N0 lung cancers with maxSUV <2.0 or pathological nodule size ≤10 mm, systematic nodal dissection can be avoided as the risk of nodal involvement is very low.

Background: We have assessed the survival rate of patients with non-small cell lung cancer and synchronous hematogenous solitary metastasis identified with complete staging workup, including total body [18F]fluorodeoxyglucose positron emission tomography scan, and treated with a multidisciplinary approach., Methods: We examined the database of all patients who underwent surgery for primary non-small cell lung cancer in our institute. The criteria required for inclusion in this analysis were diagnosis of non-small cell lung cancer with synchronous hematogenous solitary metastasis by staging workup with total body computed tomography scan and brain magnetic resonance if indicated, total body positron emission tomography scan, radical surgery for the primary tumors, local treatment of the solitary metastasis, and systemic chemotherapy administration., Results: We analyzed the data from 1,509 patients treated from January 2000 to December 2005: 10 patients (0.7%) satisfied the selection criteria. The median overall survival was 26 months, and the median time to progression was 20 months; 6 patients were alive at the time of analysis, with a median follow-up of 30 months. Four patients were tumor progression-free after 9, 18, 23, and 32 months from the start of their treatment., Conclusions: The presentation of non-small cell lung cancer with a synchronous hematogenous solitary metastasis identified by [18F]fluorodeoxyglucose positron emission tomography containing complete staging workup is extremely rare. This subset of patients can achieve long-term survival after a multidisciplinary treatment approach.