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OBJECTIVES Total thymectomy in addition to medical treatment is an accepted standard therapy for myasthenia gravis (MG). Patients with severe generalized MG present life-threatening events, poor prognosis and higher risk of postoperative myasthenic crisis. The aim of our study is to investigate neurological and surgical results in patients with Myasthenia Gravis Foundation of America (MGFA) class IV and V MG following thymectomy. METHODS Data on 76 MG patients with preoperative MGFA classes IV and V who underwent thymectomy were retrospectively collected. Primary end points included short-term surgical outcomes and long-term neurological results including the achievement of complete stable remission and any improvement as defined by MGFA Post-Intervention Status criteria. RESULTS There were 27 (35.5%) males and 49 (64.5%) females; 53 (69.7%) were classified as MGFA class IV and 23 (30.3%) as class V. Thymectomy was performed through sternotomy in 25 (32.9%) patients, Video-assisted thoracic surgery (VATS) in 5 (6.6%) and Robot-assisted thoracic surgery (RATS) in 46 (60.5%). The median operative time was 120 (interquartile range: 95; 148) min. In-hospital mortality was observed in 1 (1.3%) patient and postoperative complications in 14 (18.4%) patients. The median postoperative hospital stay was 4 (interquartile range: 3; 6) days. Pathological examination revealed 31 (40.8%) thymic hyperplasia/other benign and 45 (59.2%) thymomas. Cumulative complete stable remission and improvement probabilities were 20.6% and 83.7% at 5 years and 66.9% and 97.6% at 10 years, respectively. A significant improvement rate was found in patients with age at the time of thymectomy of ≤50 years (P = 0.0236), MGFA class V (P = 0.0154) and acetylcholine receptor antibodies positivity (P = 0.0152). CONCLUSIONS Thymectomy in patients with severe MG yields good perioperative outcomes and satisfactory long-term neurological improvement, especially for patients younger than 50 years, with MGFA class V and anti-AChR+ MG.

Thymic epithelial tumors are presently staged using a consistent TNM classification developed by the International Association for the Study of Lung Cancer (IASLC) and approved by the Union for International Cancer Control and the American Joint Committee on Cancer. The stage classification is incorporated in the eight edition of the TNM classification of thoracic malignancies. The IASLC Staging and Prognostic Factors Committee (SPFC)-Thymic Domain (TD) is in charge for the next (ninth) edition expected in 2024. The present article represents the midterm report of the SPFC-TD: in particular, it describes the unresolved issues identified by the group in the current stage classification which are worth being addressed and discussed for the ninth edition of the TNM classification on the basis of the available data collected in the central thymic database which will be managed and analyzed by Cancer Research And Biostatistics. These issues are grouped into issues of general importance and those specifically related to T, N, and M categories. Each issue is described in reference to the most recent reports on the subject, and the priority assigned by the IASLC SPFC-TD for the discussion of the ninth edition is provided.

The aim of the study is to evaluate clinical applications, safety, and effectiveness of a porcine-derived acellular cross-linked dermal matrix biological mesh in chest wall reconstruction.We retrospectively analyzed a prospective multicenter database of chest wall reconstructions using a biological mesh in adult patients undergoing operation between October 2013 and December 2020. We evaluated preoperative data, type of resection and reconstruction, hospitalization, 30-day morbidity and mortality, and overall survival.A total of 105 patients (36 women [34.2%]; mean age, 57.0 ± 16.1 years; range, 18-90 years) were included, they have admitted for: primary chest wall tumor (n = 52; 49.5%), secondary chest wall tumor (n = 29; 27.6%), lung hernia (n = 12; 11.4%), trauma (n = 10; 9.6%), and infections (n = 2; 1.9%). The surgical sites were preoperatively defined as at high risk of infection in 28 patients (26.7%) or as infected in 16 (15.2%) patients. Thirty-days morbidity was 30.5% (n = 32 patients); 14 patients (13.3%) had postoperative complications directly related to chest wall surgical resection and/or reconstruction. We experienced no 30-day mortality; 1-year and 2-year mortality was 8.4% and 16.8%, respectively.Biological mesh represents a valuable option in chest wall reconstruction even when surgical sites are infected or at high-risk of infections. This mesh shows low early and late postoperative complication rates and excellent long-term stability.

OBJECTIVESPrimary spontaneous pneumothorax is a common disease, whose surgical treatment is still enigmatic in terms of timing and technique. Herein, we reported our experience with the parenchymal-sparing technique via cold coagulation (CC), in comparison to stapler apicectomy (SA).METHODSWe retrospectively collected data of all patients with apical blebs or RESULTSOut of 177 patients enrolled, 77 patients (CC group) underwent cold-coagulation of the apex while 100 patients (SA group) were treated with SA. Two groups were comparable in terms of age, surgical indication, intraoperative findings and affected side. CC group had a mean operative time of 43.2 min (standard deviation ± 19.5), shorter than SA group with 49.3 min (standard deviation ± 20.1, P-value: 0.050). Complication rate was significantly different between 2 groups, 5 (7%) and 16 (16%), for the CC and SA groups, respectively (P: 0.048), even if not in terms of prolonged postoperative air leak (P: 0.16). During the follow-up, 13 homolateral recurrences were reported: 2 (3%) in group CC and 11 (11%) in group SA; with a significant difference (P: 0.044). All reinterventions (postoperative prolonged air leak and recurrences) required an SA.CONCLUSIONSParenchymal-sparing technique through CC of apical blebs and bullae is an effective treatment for primary spontaneous pneumothorax and guarantees a good immediate lung sealing, despite stapling still represents the choice treatment in complex cases.

Introduction The International Thymic Malignancy Interest Group (ITMIG) classifies thymoma recurrences on the basis of the topographic location, but its effectiveness in prognosis prediction has not been well investigated yet. Aims of this study are to analyze survival outcome of patients surgically treated for thymoma recurrence according to the ITMIG recurrence classification and to investigate possible alternatives. Methods From January 1, 1990, to January 7, 2017, data on 135 surgically treated patients for thymoma recurrence from three high-volume centers were collected and retrospectively analyzed. Patients were classified according to the ITMIG classification as local, regional, and distant. The ITMIG classification and alternative classifications were correlated to overall survival (OS). Results According to the ITMIG classification, recurrence was local in 17 (12.5%), regional in 97 (71.8%), and distant in 21 (15.7%) patients, with single localization in 38 (28.2%) and multiple localizations in 97 (71.8%). The 5- and 10-year OS were 79.9% and 49.7% in local, 68.3% and 52.6% in regional, and 66.3% and 35.4% in distant recurrences, respectively, but differences were not statistically significant (p = 0.625). A significant difference in survival was present considering single versus multiple localizations: 5- and 10-year OS of 86.2% and 81.2% versus 61.3% and 31.5% (p = 0.005, hazard ratio = 7.22, 95% confidence interval: 0.147–0.740), respectively. Combining the localization number with the recurrence site, ITMIG locoregional single recurrence had a statistically significant better survival compared with patients with ITMIG locoregional multiple recurrence or ITMIG distant recurrence (p = 0.028). Similarly, a significant difference was present considering intrathoracic single versus intrathoracic multiple versus distant recurrence (p = 0.024). Conclusions The ITMIG classification for thymoma recurrence did not have significant survival differences comparing local, regional, and distant recurrences. Integrating this classification with the number of the localizations may improve its effectiveness in prognosis prediction.

BACKGROUND: Thymomas can benefit of cytoreductive surgery even if a complete resection is not feasible. The pleural cavity is the most common site of progression and the resection of pleural metastases can be performed in selected patients. We evaluated the results of stereotactic body radiation therapy for the treatment of pleural metastases in patients not eligible for surgery. METHODS: We retrospectively selected 22 patients treated with stereotactic body radiation therapy for pleural metastases between 2013 and 2019. According to RECIST criteria 1.1 modified for thymic epithelial tumors, time to local failure and progression free survival were calculated using Kaplan-Meier method. RESULTS: The median age was 40 years (range, 29–73 years). There were 1 A, 3 AB, 3 B1, 3 B2, 3 B2/B3 and 9 B3 thymomas. Pleural metastases and primary tumor were synchronous in 8 patients. Five patients had a single pleural metastatic site and 17 presented multiple localizations. Sixteen patients received stereotactic body radiation therapy on multiple sites of pleural metastases. The median dose of radiation was 30 Gy (range, 24–40 Gy). With a median follow-up of 33.2 months (95% CI: 13.1–53.3 months), ten patients experienced disease progression with a median progression free survival was 20.4 months (95% CI: 10.7–30.0 months). The disease control rate was 79% and 41% after 1 and 2 years, respectively. Local disease control rate was 92% and 78% after 1 and 2 years, respectively. There were not significant differences in progression free survival between patients diagnosed with synchronous and metachronous metastases (P=0.477), across those treated or not with chemotherapy (P=0.189) and between those who received or not a previous surgical resection of the pleural metastases (P=0.871). There were not grade 3–4 toxicities related to the treatment. CONCLUSIONS: Stereotactic body radiation therapy of pleural metastases is feasible and offers a promising local control of diseases. The impact of this treatment on patients’ survival is hardly predictable because of the heterogeneous clinical behavior of thymomas.

Osteoporosis is a highly prevalent condition affecting a growing number of patients affected by chronic obstructive pulmonary disease (COPD), with crucial implications for risk of fragility fractures, hospitalization, and mortality. Several risk factors have been identified to have a role in osteoporosis development in COPD patients, including corticosteroid therapy, systemic inflammation, smoke, physical activity levels, malnutrition, and sarcopenia. In this scenario, a personalized multitarget intervention focusing on the pathological mechanisms underpinning osteoporosis is mandatory to improve bone health in these frail patients. Specifically, physical exercise, nutritional approach, dietary supplements, and smoke cessation are the cornerstone of the lifestyle approach to osteoporosis in COPD patients, improving not only bone health but also physical performance and balance. On the other hand, pharmacological treatment should be considered for both the prevention and treatment of osteoporosis in patients at higher risk of fragility fractures. Despite these considerations, several barriers still affect the integration of a personalized approach to managing osteoporosis in COPD patients. However, digital innovation solutions and telemedicine might have a role in optimizing sustainable networking between hospital assistance and community settings to improve bone health and reduce sanitary costs of the long-term management of COPD patients with osteoporosis.

Objective The presence of micropapillary and solid adenocarcinoma patterns leads to a worse survival and a significantly higher tendency to recur. This study aims to assess the impact of pT descriptor combined with the presence of high-grade components on long-term outcomes in early-stage lung adenocarcinomas. Methods We retrospectively collected data of consecutive resected pT1-T3N0 lung adenocarcinoma from nine European Thoracic Centers. All patients who underwent a radical resection with lymph-node dissection between 2014 and 2017 were included. Differences in Overall Survival (OS) and Disease-Free Survival (DFS) and possible prognostic factors associated with outcomes were evaluated also after performing a propensity score matching to compare tumors containing non-high-grade and high-grade patterns. Results Among 607 patients, the majority were male and received a lobectomy. At least one high-grade histological pattern was seen in 230 cases (37.9%), of which 169 solid and 75 micropapillary. T1a-b-c without high-grade pattern had a significant better prognosis compared to T1a-b-c with high-grade pattern (p = 0.020), but the latter had similar OS compared to T2a (p = 0.277). Concurrently, T1a-b-c without micropapillary or solid patterns had a significantly better DFS compared to those with high-grade patterns (p = 0.034), and it was similar to T2a (p = 0.839). Multivariable analysis confirms the role of T descriptor according to high-grade pattern both for OS (p = 0.024; HR 1.285 95% CI 1.033–1.599) and DFS (p = 0.003; HR 1.196, 95% CI 1.054–1.344, respectively). These results were confirmed after the propensity score matching analysis. Conclusions pT1 lung adenocarcinomas with a high-grade component have similar prognosis of pT2a tumors.

Backgrounds Oligometastatic Non-Small Cell Lung Cancer (NSCLC) patients represent a category without a standard therapeutic approach. However, in selected oligometastatic NSCLC, radical surgery seems to offer a good prognosis. This retrospective study aimed to analyse the long-term outcomes of synchronous oligometastatic patients treated with curative intent and identify the factors associated with better results and the proposal of a risk stratification system for classifying the synchronous oligometastatic NSCLC. Methods The medical records of patients from 18 centres with pathologically diagnosed synchronous oligometastatic NSCLC were retrospectively reviewed. The inclusion criteria were synchronous oligometastatic NSCLC, radical surgical treatment of the primary tumour with or without neoadjuvant/adjuvant therapy and radical treatment of all metastatic sites. The Kaplan – Meier method estimated survivals. A stratified backward stepwise Cox regression model was assessed for multivariable survival analyses. Results 281 patients were included. The most common site of metastasis was the brain, in 50.89 % patients. Median overall survival was 40 months (95 % CI: 29–53). Age ≤65 years (HR = 1.02, 95 % CI: 1.00–1.05; p = 0.019), single metastasis (HR = 0.71, 95 % CI: 0.45–1.13; p = 0.15) and presence of contralateral lung metastases (HR = 0.30, 95 % CI: 0.15 – 0.62; p = 0.001) were associated with a good prognosis. The presence of pathological N2 metastases negatively affected survival (HR = 2.00, 95 % CI: 1.21–3.32; p = 0.0065). These prognostic factors were used to build a simple risk classification scheme. Conclusions Treatment of selected synchronous oligometastatic NSCLC with curative purpose could be conducted safely and at acceptable 5-year survival levels, especially in younger patients with pN0 disease.

OBJECTIVES This study reports the results of an international expert consensus process evaluating the assessment of intraoperative air leaks (IAL) and treatment of postoperative prolonged air leaks (PAL) utilizing a Delphi process, with the aim of helping standardization and improving practice. METHODS A panel of 45 questions was developed and submitted to an international working group of experts in minimally invasive lung cancer surgery. Modified Delphi methodology was used to review responses, including 3 rounds of voting. The consensus was defined a priori as >50% agreement among the experts. Clinical practice standards were graded as recommended or highly recommended if 50–74% or >75% of the experts reached an agreement, respectively. RESULTS A total of 32 experts from 18 countries completed the questionnaires in all 3 rounds. Respondents agreed that PAL are defined as >5 days and that current risk models are rarely used. The consensus was reached in 33/45 issues (73.3%). IAL were classified as mild (400 ml/min; 74%). If mild IAL are detected, 68% do not treat; if moderate, consensus was not; if severe, 90% favoured treatment. CONCLUSIONS This expert consensus working group reached an agreement on the majority of issues regarding the detection and management of IAL and PAL. In the absence of prospective, randomized evidence supporting most of these clinical decisions, this document may serve as a guideline to reduce practice variation.

The current COVID-19 pandemic has shown a relevant rate of patients developing an acute respiratory distress syndrome that requires hospitalization. Approximately 3-17% of hospitalized patients require Intensive Care Unit (ICU) and invasive mechanical ventilation. Initial recommendations advocated for early intubation, while early tracheotomy should not be routinely performed in COVID-19 patients. We report the case of a COVID-19 patient developing laryngo-tracheal stenosis secondary to an open surgical tracheotomy in the ICU. A conservative endoscopic management was not successful and we performed a laryngo-tracheal resection. The specimen was negative for COVID-19 but the pathological examination revealed how the virus damaged the trachea. This case is, as far as we are aware, the first case of laryngo-tracheal surgery in a COVID-19 patient and provides an insight to justify the higher rate of tracheal injuries occurring in intubated COVID-19 patients.

Background Thymoma‐associated myasthenia gravis (TAMG) is one of the subtypes of myasthenia gravis with autoantibodies against the acetylcholine receptor (AChR‐Ab). We analyzed the clinical features of our cohort of TAMG patients and the changes in AChR‐Ab titer before and after thymectomy in order to identify factors predicting thymoma relapses. Methods We retrospectively assessed: age of MG onset, MG clinical status according to MGFA (Myasthenia Gravis Foundation of America), epoch of thymectomy, post‐thymectomy status, oncological features and surgical approach. AChR‐Ab dosages were measured both before and after thymectomy. Linear regression models were applied to identify clinical determinants of AChR‐Ab titers and the Cox regression model was fitted to estimate the factors associated with the risk of thymoma recurrence. Results The study sample included 239 MG patients, 27 of whom experienced one or more recurrences (median follow‐up time: 4.8 years). The AChR‐Ab titers decreased after first thymectomy (P, In our paper, we retrospectively analyzed the changes in antiacetylcholine receptor antibody (AChR‐Ab) titer before and after thymectomy and the clinical features of thymoma‐associated myasthenia gravis (TAMG) patients in order to identify clinical and serological predictors of thymoma recurrence. Our study emphasizes the importance of a multidisciplinary approach among Neurologists, Oncologists and Thoracic Surgeons, and identifies subgroups of MG patients with high risk of thymoma recurrence who therefore need a more accurate follow‐up.

Objective: Our aim was to validate the prognostic relevance in NSCLC of potential residual tumor (R) descriptors, including the proposed International Association for the Study of Lung Cancer definition for uncertain resection, referred to as R(un). Methods: A total of 14,712 patients undergoing resection with full R status and survival were analyzed. The following were also evaluated: whether fewer than three N2 stations were explored, lobe-specific nodal dissection, extracapsular extension, highest lymph node station status, carcinoma in situ at the bronchial resection margin, and pleural lavage cytologic examination result. Revised categories of R0, R(un), R1, and R2 were tested for survival impact. Results: In all, 14,293 cases were R0, 263 were R1, and 156 were R2 (median survivals not reached, 33 months, and 29 months, respectively). R status correlated with T and N categories. A total of 9290 cases (63%) had three or more N2 stations explored and 6641 cases (45%) had lobespecific nodal dissection, correlated with increasing pN2. Extracapsular extension was present in 62 of 364 cases with available data (17%). The highest station was positive in 942 cases (6.4%). The pleural lavage cytologic examination result was positive in 59 of 1705 cases (3.5%): 13 had carcinoma in situ at the bronchial resection margin. After reassignment because of inadequate nodal staging in 56% of cases, 6070 cases were R0, 8185 were R(un), 301 were R1, and 156 were R2. In node-positive cases, the median survival times were 70, 50, and 30 months for RO, R(un) (p < 0.0001), and R1 (p < 0.001), respectively, with no significant difference between RO and R(un) in pN0 cases. Conclusions: R descriptors have prognostic relevance, with R(un) survival stratifying between R0 and R1. Therefore, a detailed evaluation of R factor is of particular importance in the design and analyses of clinical trials of adjuvant therapies. (C) 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

OBJECTIVES Lung cancer is increasingly diagnosed as a second cancer. Our goal was to analyse the characteristics and outcomes of early-stage resected lung adenocarcinomas in patients with previous cancers (PC) and correlations with adenocarcinoma subtypes. METHODS We retrospectively reviewed data of patients radically operated on for stage I–II lung adenocarcinoma in 9 thoracic surgery departments between 2014 and 2017. Overall survival (OS) and time to disease relapse were evaluated between subgroups. RESULTS We included 700 consecutive patients. PC were present in 260 (37.1%). Breast adenocarcinoma, lung cancer and prostate cancer were the most frequent (21.5%, 11.5% and 11.2%, respectively). No significant differences in OS were observed between the PC and non-PC groups (P = 0.378), with 31 and 75 deaths, respectively. Patients with PC had smaller tumours and were more likely to receive sublobar resection and to be operated on with a minimally invasive approach. Previous gastric cancer (P = 0.042) and synchronous PC (when diagnosed up to 6 months before lung adenocarcinoma; P = 0.044) were related, with a worse OS. Colon and breast adenocarcinomas and melanomas were significantly related to a lower incidence of high grade (solid or micropapillary, P = 0.0039, P = 0.005 and P = 0.028 respectively), whereas patients affected by a previous lymphoma had a higher incidence of a micropapillary pattern (P = 0.008). CONCLUSIONS In patients with PC, we found smaller tumours more frequently treated with minimally invasive techniques and sublobar resection, probably due to a more careful follow-up. The impact on survival is not uniform and predictable; however, breast and colon cancers and melanoma showed a lower incidence of solid or micropapillary patterns whereas patients with lymphomas had a higher incidence of a micropapillary pattern.

Introduction: Malignant Pleural Mesothelioma (MPM) is characterized by an aggressive behavior and an inevitably fatal prognosis, whose treatment is still far from being standardized. The role of surgery is questionable since a radical resection is unattainable in most cases. Hyperthermic IntraTHOracic Chemotherapy (HITHOC) combines the advantages of antitumoral effects together with those of high temperature on the exposed tissues with the aim to improve surgical radicality. Material and Methods: this is a narrative review on the role of HITHOC in the management of MPM patients. To provide data on the beginnings and the historical evolution of this technique, we searched the available literature by selecting the more exhaustive papers on this topic. Results: from 1994 to date different authors experimented HITHOC following a cytoreductive surgery in MPM, obtaining in most cases a good local control and a better overall survival associated to very low complication rate. Conclusions: HITHOC may be considered as a safe, feasible and effective procedure although there is a high heterogeneity between different protocols adopted worldwide. More structured studies are needed to reach a unanimous consensus on this technique.

Extracorporeal membrane oxygenation (ECMO) is a form of cardiopulmonary life-support, and may be very useful in selected cases as traumatic tracheo-bronchial injuries, allowing an efficient gas exchange where ventilation is not feasible. Even if, nowadays, little used, ECMO is an additional arrow in the quiver of the doctors, especially in challenging cases.

The Masoka-Koga and tumor node metastases staging systems for thymoma are based on structures involved, but the prognostic role of the number of infiltrated/involved structures is still debated. We analyzed the prognostic role of involved structures and their combinations in locally advanced thymomas patients.Data on 174 surgically treated locally advanced thymoma patients from 1/01/1990 to 31/12/2015 were reviewed. Clinical and pathological characteristic, involved structures, number of involved structures and different combinations were correlated to cancer specific survival (CSS) using Kaplan-Meier product-limit method.Five and 10-year CSS was 92% and 87%. Masaoka Stage 3 (p 0.001), absence of pericardial involvement (p = 0.001), number of involved structures (p = 0.018), R0 (p 0.001) and adjuvant radiotherapy (p = 0.008) were favorable prognostic CSS factors. A significant better prognosis was present in ≤2 involved structures vs2 involved structures (5- and 10-year CSS: 95% and 93% vs. 80% and 51%). Multivariable analysis confirmed as independent prognostic factor R0 (p = 0.033, hazard ratio [HR]: 0.093, 95% confidence interval [CI] 0.010-0.827) and number of involved structures (p = 0.046, HR: 0.187, 95% CI: 0.036-0.968). In Masaoka Stage 3, patients with ≤2 involved structures had a significant better CSS than patients with2 (10-year CSS: 98% vs. 73%, p = 0.008).The number of involved structures and the concomitant involvement of the pericardium seems to be associated with a poor prognosis in surgically treated advanced thymoma patients.

Background: Malignant pleural mesothelioma (MPM) is a fatal tumor with a poor prognosis. The recent developments of liquid biopsies could provide novel diagnostic and prognostic tools in oncology. However, there is limited information about the feasibility of this technique for MPMs. Here, we investigate whether cancer-specific DNA sequences can be detected in pleural fluids and plasma of MPM patients as free circulating tumor DNA (ctDNA). Methods: We performed whole-exome sequencing on 14 tumor biopsies from 14 patients, and we analyzed 20 patient-specific somatic mutations with digital droplet PCR (ddPCR) in pleural fluids and plasma, using them as cancer-specific tumor biomarkers. Results: Most of the selected mutations could be detected in pleural fluids (94%) and, noteworthy, in plasma (83%) with the use of ddPCR. Pleural fluids showed similar levels of somatically mutated ctDNA (median = 12.75%, average = 16.3%, standard deviation = 12.3) as those detected in solid biopsies (median = 21.95%, average = 22.21%, standard deviation = 9.57), and their paired difference was weakly statistically significant (p = 0.048). On the other hand, the paired difference between solid biopsies and ctDNA from plasma (median = 0.29%, average = 0.89%, standard deviation = 1.40) was highly statistically significant (p = 2.5 × 10−7), corresponding to the important drop of circulating somatically mutated DNA in the bloodstream. However, despite the tiny amount of ctDNA in plasma, varying from 5.57% down to 0.14%, the mutations were detectable at rates similar to those possible for other tumors. Conclusions: We found robust evidence that mutated DNA is spilled from MPMs, mostly into pleural fluids, proving the concept that liquid biopsies are feasible for MPM patients.

Importance Full-thickness tracheal lesions and tracheoesophageal fistulas are severe complications of invasive mechanical ventilation. The incidence of tracheal complications in ventilated patients with coronavirus disease 2019 (COVID-19) is unknown. Objective To evaluate whether patients with COVID-19 have a higher incidence of full-thickness tracheal lesions and tracheoesophageal fistulas than matched controls and to investigate potential mechanisms. Design, Setting, and Participants This is a retrospective cohort study in patients admitted to the intensive care unit in a tertiary referral hospital. Among 98 consecutive patients with COVID-19 with severe respiratory failure, 30 underwent prolonged (≥14 days) invasive mechanical ventilation and were included in the COVID-19 group. The control group included 45 patients without COVID-19. Patients with COVID-19 were selected from March 1 to May 31, 2020, while the control group was selected from March 1 to May 31, 2019. Exposures Patients with COVID-19 had severe acute respiratory syndrome coronavirus 2 infection diagnosed by nasopharyngeal/oropharyngeal swabs and were treated according to local therapeutic procedures. Main Outcomes and Measures The primary study outcome was the incidence of full-thickness tracheal lesions or tracheoesophageal fistulas in patients with prolonged invasive mechanical ventilation. Results The mean (SD) age was 68.8 (9.0) years in the COVID-19 group and 68.5 (14.1) years in the control group (effect size, 0.3; 95% CI, −5.0 to 5.6). Eight (27%) and 15 (33%) women were enrolled in the COVID-19 group and the control group, respectively. Fourteen patients (47%) in the COVID-19 group had full-thickness tracheal lesions (n = 10, 33%) or tracheoesophageal fistulas (n = 4, 13%), while 1 patient (2.2%) in the control group had a full-thickness tracheal lesion (odds ratio, 38.4; 95% CI, 4.7 to 316.9). Clinical and radiological presentations of tracheal lesions were pneumomediastinum (n = 10, 71%), pneumothorax (n = 6, 43%), and/or subcutaneous emphysema (n = 13, 93%). Conclusions and Relevance In this cohort study, almost half of patients with COVID-19 developed full-thickness tracheal lesions and/or tracheoesophageal fistulas after prolonged invasive mechanical ventilation. Attempts to prevent these lesions should be made and quickly recognized when they occur to avoid potentially life-threatening complications in ventilated patients with COVID-19.

Objective: To evaluate the influence of lung adenocarcinoma second predominant pattern on the maximal standard uptake value (SUVmax) and its prognostic effect in different histologic groups. Methods: We retrospectively collected surgically resected pathologic stage I and II lung adenocarcinoma from nine European institutions. Only patients who underwent preoperative PET-CT and with available information regarding SUVmax of T (SUVmaxT) and N1 (SUVmaxN1) component were included. Results: We enrolled 344 patients with lung adenocarcinoma. SUVmaxT did not show any significant relation according to the second predominant pattern ( p = 0.139); this relationship remained nonsignificant in patients with similar predominant pattern. SUVmaxT influenced the disease-free survival in the whole cohort ( p = 0.002) and in low- and intermediate-grade predominant pattern groups ( p = 0.040 and p = 0.008, respectively). In the high-grade predominant pattern cohort and in the pathologic N1 cases, SUVmaxT lost its prognostic power. SUVmaxN1 did not show any significant correlation with predominant and second predominant patterns and did not have any prognostic impact on DFS. Conclusions: SUVmaxT is influenced only by the adenocarcinoma predominant pattern, but not by second predominant pattern. Concurrently, in high-grade predominant pattern and pN1 group the prognostic power of SUVmaxT becomes nonsignificant.

In this paper we aimed to address the role of pulmonary metastasectomy (PM) in patients affected by Lung Metastases (LM) from Renal Cell Carcinoma (RCC) and to analyse prognostic factors affecting overall survival (OS), disease-free interval (DFI) between primary RCC and first LM, and disease-free survival (DFS) after PM and before lung recurrence. Medical records of 210 patients who underwent PM from RCC in 4 Italian Thoracic Centres, from January 2000 to September 2019, were collected and analysed. All patients underwent RCC resection before lung surgery. The main RCC histology was clear cells (188, 89.5%). The 5- and 10-year OS from the first lung operation were 60% and 34%, respectively. LM synchronous with RCC (p = 0.01) and (Karnofsky Performance Status Scale) KPSS &lt, 80% (p &lt, 0.001) negatively influenced OS. Five- and 10-year DFI were 54% and 28%, respectively. The main factors negatively influencing DFI were: male gender (p = 0.039), KPSS &lt, 80% (p = 0.009) and lactate dehydrogenase &gt, 1.5 times 140 U/L (p = 0.001). Five- and 10-year disease-free survival were 54% and 28%, respectively, multiple LM (p = 0.036), KPSS &lt, 80% (p = 0.001) and histology of RCC other than clear cells negatively influenced disease-free survival. Conclusions: patients with KPSS &gt, 80%, single metachronous LM with a long DFI from RCC diagnosis, and clear cell histology, benefit from pulmonary metastasectomy.

Background and objectives Adenocarcinoma patterns could be grouped based on clinical behaviors: low- (lepidic), intermediate- (papillary or acinar), and high-grade (micropapillary and solid). We analyzed the impact of the second predominant pattern (SPP) on disease-free survival (DFS). Methods We retrospectively collected data of surgically resected stage I and II adenocarcinoma. Selection criteria anatomical resection with lymphadenectomy and pathological N0. Pure adenocarcinomas and mucinous subtypes were excluded. Recurrence rate and factors affecting DFS were analyzed according to the SPP focusing on intermediate-grade predominant pattern adenocarcinomas. Results Among 270 patients, 55% were male. The mean age was 68.3 years. SPP pattern appeared as follows: lepidic 43.0%, papillary 23.0%, solid 14.4%, acinar 11.9%, and micropapillary 7.8%. The recurrence rate was 21.5% and 5-year DFS was 71.1%. No difference in DFS was found according to SPP (p = .522). In patients with high-grade SPP, the percentage of SPP, age, and tumor size significantly influenced DFS (p = .016). In patients with lepidic SPP, size, male gender, and lymph-node sampling (p = .005; p = .014; p = .038, respectively) significantly influenced DFS. Conclusions The impact of SPP on DFS is not homogeneous in a subset of patients with the intermediate-grade predominant patterns. The influence of high-grade SPP on DFS is related to its proportion in the tumor.

OBJECTIVE: With this narrative review, we retraced the history of hypertermic intrathoracic chemotherapy (HITHOC) since the beginning, analyzing literature on operative technique, feasibility and efficacy of this treatment. Moreover, we report the fifteen-year experience of our center in this relatively new technique, for what concerns both early postoperative results and long-term oncological outcomes. BACKGROUND: Thymomas are frequently misdiagnosed and recognized in advanced stage, often with pleural dissemination, especially when not associated to Myasthenia Gravis that allows an early diagnosis during the initial assessment. Moreover, the natural history of locally advanced thymoma is characterized by a high rate of pleural or pericardial relapses. Surgery has always been considered a milestone in thymoma’s treatment, even in case of serous dissemination or relapses, although his role as exclusive therapy does not guarantee an acceptable local disease control. In case of disseminated disease, different multidisciplinary protocols have been experimented, from chemotherapy to radiation therapy, alone or associated to surgery, in order to increase overall and disease-free survival, but the breakthrough happened in the early 90s with the introduction of HITHOC following surgery. Combination of surgery and HITHOC resulted in less toxic than systemic chemotherapy and providing a good local disease control in patients with stage IVa thymomas or thymoma’s pleural recurrences. METHODS: We searched PubMed for relevant literature, up to January 2020, on hypertermic intrapleural chemotherapy for thymomas (TPR or DNT), selecting only those reporting information about HITHOC protocol used, postoperative course and oncological outcomes. CONCLUSIONS: HITHOC is a safe and feasible procedure, with a very low complication rate and negligible systemic effects of chemotherapeutic agents, effective in controlling both TPR and DNT, in particular as regards local disease-free survival. KEYWORDS: Hypertermic intrathoracic chemotherapy (HITHOC); thymoma; intracavitary chemotherapy; hyperthermia; redo-surgery

Background: In previous multicentre studies, the longest survival was observed in synchronous lung oligometastatic patients without pN2 disease. This paper aimed to identify preoperative favourable prognostic factors and propose a preoperative classification for categorising the synchronous oligometastatic non-small cell lung cancer (NSCLC). Methods: A retrospective review of prospectively collected patients was performed. The inclusion criteria were: synchronous oligometastatic NSCLC (≤5 extrapulmonary metastases), radical surgical treatment of the primary tumour and all metastatic sites (2005–2018). Exclusion criteria were: palliative surgery, recurrent lung cancer, low-performance status, follow-up information unavailable. The reverse Kaplan – Meier method estimated median overall survival (OS) and progression-free survival. A stratified backward stepwise Cox regression model was employed for multivariable survival analyses. A prognostic grouping considering all the relevant prognostic factors simultaneously was constructed, and a Receiver Operating Characteristic (ROC) curve was generated. Hosmer-Lemeshow χ statistics was used for measuring OS calibration within groups. Findings: 281 patients were included. Data from the Cox regression model were used to construct a prognostic risk classification. Four parameters (age ≤65 years, site of metastasis, clinical nodal status, and induction treatment) were used to build a risk classification. Group A: no risk factors (age ≤65 years, lung/brain metastasis, cN0, induction treatment); Group B: one risk factor (age >65 years or no lung/brain metastasis or cN1–2 or no induction treatment); Group C: two risk factors; Group D: ≥3 risk factors. The Area Under the Curve (AUC) was 0.56 (95% CI: 0.49–0.62), Hosmer-Lemeshow χ statistics was 21.3 (3 degrees of freedom, p=0.0042). Interpretations: Patient selection is critical in identifying the proper subsets of oligometastatic NSCLC. After clinical validation, this preoperative risk classification might support decision-making during the multidisciplinary team assessment and patient selection for enrolment in future randomised trials. Funding: This work was partially supported by the Italian Ministry of Health with Ricerca Corrente and 5 x 1000 funds. Declaration of Interest: All authors have no conflict of interest to declare. Ethical Approval: This research was carried out following the Helsinki Declaration 10. The Ethical Committee authorised the study (785/19).