Surgical Decision Making: Thymoma and Myasthenia Gravis

About 15% of patients with myasthenia gravis are affected by thymoma. Precise tumor staging is necessary to plan the appropriate operation. In early stages, complete surgical resection is the mainstay of treatment. Minimally invasive approaches can be safely performed by highly trained surgeons, and may be preferred in myasthenic patients because they can ensure optimal results from the oncological, neurologic, and surgical point of views, avoiding the complications of open approach. For advanced stage thymoma in myasthenic patients, a careful, multidisciplinary planning of the therapeutic approach must be undertaken, particularly for extended resections involving the lung and great vessels

Predictors of unexpected nodal upstaging in patients with cT1-3N0 non-small cell lung cancer (NSCLC) submitted to thoracoscopic lobectomy

In the last decades, the use of video-assisted thoracoscopic surgery (VATS) lobectomy for the treatment of early stage non-small cell lung cancer is continuously growing. This is mainly due to the development of more advanced surgical devices, to the rising incidence of peripheral lung tumors and is also favored by the increased reliability of preoperative staging techniques. Despite this progress, postoperative unexpected nodal upstaging is still a relevant issue. Aim of this study is to identify possible predictors of unexpected nodal upstaging in patients affected by cT1-3N0 NSCLC submitted to VATS lobectomy

Robotic thymectomy for myasthenia gravis

Thymectomy is an effective treatment option for the management of myasthenia gravis, as demonstrated by a recent multicenter randomized clinical trial. Complete removal of all thymic tissue, including ectopic foci, increases the chance of achieving a remission or a substantial improvement of the disease; therefore, extended transsternal thymectomy was long considered the procedure of choice. Over the years, several minimally invasive approaches have been proposed, with the aim to reduce perioperative morbidity and to improve aesthetics; however, concerns exist that through such approaches, it may not be possible to achieve a complete resection. Robotic thymectomy seems to overcome many of the limitations associated with other minimally invasive approaches. The available evidence suggests that robotic thymectomy for myasthenia gravis is a safe procedure, and that long-term neurological outcomes are satisfactory

Robotic-assisted thymectomy: current perspectives

Thymectomy is the cornerstone in the treatment of thymic tumors and an accepted option for the management of myasthenia gravis. Different surgical approaches have been described, but the gold standard is represented by median sternotomy. In the last two decades, the development of minimally invasive surgery has led to an increased acceptance of thymectomy, especially for benign diseases. Robotic thymectomy seems a further step in the development and evolution of minimally invasive approaches. Since its introduction, different authors described their experience with robotic thymectomy, both for nonthymomatous myasthenia gravis and for thymic tumors. Available data show that robotic thymectomy may be considered a safe and feasible operation. In patients with nonthymomatous myasthenia, robotic thymectomy is effective and the long-term results are encouraging. The role of robotic thymectomy in patients affected by thymoma is still under evaluation, but the intermediate results seem promising both in terms of surgical and oncologic outcomes

Multi-institutional European experience of robotic thymectomy for thymoma.

BACKGROUND: Robotic thymectomy for early-stage thymomas has been recently suggested as a technically sound and safe approach. However, due to a lack of data on long term results, controversy still exists regarding its oncological efficacy. In this multi-institutional series collected from four European Centres with high volumes of robotic procedures, we evaluate the results after robot-assisted thoracoscopic thymectomy for thymoma. METHODS: Between 2002 and 2014, 134 patients (61 males and 73 females, median age 59 years) with a clinical diagnosis of thymoma were operated on using a left-sided (38%), right-sided (59.8%) or bilateral (2.2%) robotic approach. Seventy (52%) patients had associated myasthenia gravis (MG). RESULTS: The average operative time was 146 minutes (range, 60-353 minutes). Twelve (8.9%) patients needed open conversion: in one case, a standard thoracoscopy was performed after robotic system breakdown, and in six cases, an additional access was required. Neither vascular and nerve injuries, nor perioperative mortality occurred. A total of 23 (17.1%) patients experienced postoperative complications. Median hospital stay was 4 days (range, 2-35 days). Mean diameter of resected tumors was 4.4 cm (range, 1-10 cm), Masaoka stage was I in 46 (34.4%) patients, II in 71 (52.9%), III in 11 (8.3%) and IVa/b in 6 (4.4%) cases. At last follow up, 131 patients were alive, three died (all from non-thymoma related causes) with a 5-year survival rate of 97%. One (0.7%) patient experienced a pleural recurrence. CONCLUSIONS: Our data suggest that robotic thymectomy for thymoma is a technically feasible and safe procedure with low complication rates and short hospital stays. Oncological outcome appears to be good, particularly for early-stage tumors, but a longer follow-up period and more cases are necessary in order to consider this as a standard approach. Indications for robotic thymectomy for stage III or IVa thymomas are rare and should be carefully evaluated

Multicenter randomized study on the comparison between electronic and traditional chest drainage systems

Background: In patients submitted to major pulmonary resection, the postoperative length of stay is mainly influenced by the duration of air leaks and chest tube removal. The measurement of air leaks largely relies on traditional chest drainage systems which are prone to subjective interpretation. Difficulty in differentiating between active air leaks and bubbles due to a pleural space effect may also lead to tentative drain clamping and prolonged time for chest drain removal. New digital systems allow continuous monitoring of air leaks, identifying subtle leakage that may be not visible during daily patient evaluation. Moreover, an objective assessment of air leaks may lead to a reduced interobserver variability and to an optimized timing for chest tube removal.Methods: This study is a prospective randomized, interventional, multicenter trial designed to compare an electronic chest drainage system (Drentech (TM) Palm Evo) with a traditional system (Drentech (TM) Compact) in a cohort of patients undergoing pulmonary lobectomy through a standard three-port video-assisted thoracic surgery approach for both benign and malignant disease. The study will enroll 382 patients in three Italian centers. The duration of chest drainage and the length of hospital stay will be evaluated in the two groups. Moreover, the study will evaluate whether the use of a digital chest system compared with a traditional system reduces the interobserver variability. Finally, it will evaluate whether the digital drain system may help in distinguishing an active air leak from a pleural space effect, by the digital assessment of intrapleural differential pressure, and in identifying potential predictors of prolonged air leaks.Discussion: To date, few studies have been performed to evaluate the clinical impact of digital drainage systems. The proposed prospective randomized trial will provide new knowledge to this research area by investigating and comparing the difference between digital and traditional chest drain systems. In particular, the objectives of this project are to evaluate the feasibility and usefulness of digital chest drainages and to provide new tools to identify patients at higher risk of developing prolonged air leaks

Does Induction Therapy Increase Anastomotic Complications in Bronchial Sleeve Resections?

BackgroundSleeve lobectomy represents a safe and effective treatment for central NSCLC to avoid the risks of pneumonectomy. Induction therapy (IT) may be indicated in advanced stages; however, the effect of IT on bronchial anastomoses remains uncertain. The purpose of the study was to evaluate the impact of IT on the complications of the anastomoses.MethodsBetween 2000 and 2012, 159 consecutive patients were submitted to sleeve lobectomy for NSCLC at our Institution. We retrospectively compared the results of patients who underwent IT before operation with those who received upfront surgery.ResultsIn the study period, 49 (30.8%) patients received IT (37 chemotherapy, 1 radiotherapy and 11 chemo-radiotherapy) and 110 (69.2%) patients were directly submitted to surgery (S). The two groups were comparable for sex, age, comorbidities, ASA score, pulmonary function, side, type of procedure and histology. Pathological stage was statistically higher for IT group (p=0.001). No differences between IT and S groups were observed in terms of post-operative mortality (2% vs 0%, p=NS), morbidity (45% vs 38%, p=NS), including early (6% vs 9%, p=NS) and long-term (16% vs 14%, p=NS) bronchial complication rates. Patients undergoing induction mediastinal radiotherapy, however, are at higher risk of bronchial complications.ConclusionIn our experience, the use of induction chemotherapy did not significantly increase mortality and morbidity rates, in particular, neither for early nor for late anastomotic complications. We, therefore, conclude that sleeve lobectomy after induction chemotherapy is safe and reliable procedure for the treatment of locally advanced NSCLC

The role of immune microenvironment in small-cell lung cancer: Distribution of PD-L1 expression and prognostic role of FOXP3-positive tumour infiltrating lymphocytes

INTRODUCTION: The prognosis of small-cell lung cancer (SCLC) is dismal and new effective therapies are needed. Immunotherapy looks promising, but no molecular predictive markers are currently available, and data on immune microenvironment are very limited. METHODS: We retrospectively analysed 104 SCLC cases. Immunohistochemistry evaluation of PD-L1 was performed both on tumour cells (TCs) and on tumour-infiltrating immune cells (TIICs) by using anti-PD-L1 22C3 antibody (DAKO) and categorised by using 1% as cut-off point. Tumour-infiltrating lymphocytes (TILs) were characterised by using anti-CD8 and anti-FOXP3 antibodies. Semi-quantitative score was used and categorised as positive versus negative/low. The relation of molecular markers with prognosis and with clinical variables was evaluated. RESULTS: The analysis included 66 stage I-III patients (48 surgically resected, 18 treated with radical-intent chemoradiotherapy) and 38 metastatic cases. In the overall study population, PD-L1 was expressed on TCs and TIICs in 25% and 40% of cases, respectively. The proportion of PD-L1-positive cases was significantly higher in stage I-III versus metastatic patients (32% versus 13%, p: 0.034 for TCs; 51.5% versus 21% for TIICs, p: 0.002). CD8- and FOXP3-positive TILs were present in 59% and 72% of samples, respectively. The presence of FOXP3-TILs was associated with improved prognosis among non-metastatic patients, with a hazard ratio for survival of 0.32 (95% confidence interval [CI]: 0.16-0.7, p: 0.006) for univariate analysis, and 0.37 (95% CI: 0.17-0.81, p: 0.013) for multivariate analysis. CONCLUSIONS: Immune contexture of SCLC may differ according to stage. The presence of FOXP3-positive TILs is a potential prognostic marker for stage I-III SCLCs and warrants further investigation

Molecular Profiling of Tissue Samples with Chronic Rejection from Patients with Chronic Lung Allograft Dysfunction: A Pilot Study in Cystic Fibrosis Patients

Chronic rejection (CR) is the main culprit for reduced survival and quality of life in patients undergoing lung transplantation (Ltx). High-throughput approaches have been used to unveil the molecular pathways of CR, mainly in the blood and/or in bronchoalveolar lavage. We hypothesized that a distinct molecular signature characterizes the biopsies of recipients with clinically confirmed histological signs of CR. Eighteen cystic fibrosis patients were included in the study and RNA sequencing was performed in 35 scheduled transbronchial biopsies (TBBs): 5 with acute cellular rejection, 9 with CR, and 13 without any sign of post-LTx complication at the time of biopsy; 8 donor lung samples were used as controls. Three networks with 33, 26, and 36 differentially expressed genes (DEGs) were found in TBBs with CR. Among these, seven genes were common to the identified pathways and possibly linked to CR and five of them (LCN2, CCL11, CX3CL1, CXCL12, MUC4) were confirmed by real-time PCR. Immunohistochemistry was significant for LCN2 and MUC4. This study identified a typical gene expression pattern in TBBs with histological signs of CR and the LCN2 gene appeared to play a central role. Thus, it could be crucial in CR pathophysiology