N2 lung cancer is not all the same: an analysis of different prognostic groups.

OBJECTIVES: The International Association for the Study of Lung Cancer (IASLC) recently proposed a change in the staging system for N2, based on the metastatic station number: N2a1 (a single metastatic station with no hilar involvement), N2a2 (a single metastatic station with hilar involvement) and N2b (multiple metastatic stations). The aim of our study was to validate the IASLC proposal in a cohort of patients with pathological N2 disease. METHODS: All patients with pathological T1-T2 N2 non-small-cell lung cancer who were operated on between 2006 and 2010 in our department were enrolled. The patients had lobectomy, bilobectomy or pneumonectomy without induction therapy; patients with any type of extended resection were excluded. All patients had adjuvant treatment. The impact of the new IASLC proposal on the overall and disease-free survival rates was then analysed. RESULTS: Ninety-three patients were selected. The median follow-up period and overall survival time were 92 and 28.8 months, respectively. According to the new IASLC proposal, we observed 22 cases of N2a1, 54 N2a2 and 17 N2b. Patients with N2a1 had a significantly better overall survival than those with N2a2 and N2b (P = 0.041); the difference between N2a2 and N2b was not significant (P = 0.19). Patients with N2a1 squamous cell carcinoma had a significantly better overall survival than those with other histological diagnoses (P = 0.046). The disease-free interval was longer in patients with N2a1 than those in other groups (P = 0.021). CONCLUSIONS: Our experience partially validates the IASLC proposal; the introduction of quantitative criteria for N staging might improve stratification of patients and the assignment to the correct therapeutic path.

Differential microRNA expression profiles between young and old lung adenocarcinoma patients.

Lung cancer is the leading cause of cancer-related mortality, and approximately 80% of cases are non-small cell lung cancer (NSCLC). Recently, the incidence of NSCLC has been quickly increasing, while the age of patients at diagnosis is decreasing. To date, it is still controversial whether younger patients have better or worse outcomes compared with their older counterparts. MicroRNAs (miRNAs) have been defined to play a key role in cancer pathogenesis, and their aberrant expression has been suggested as a potential biomarker of prognosis in lung adenocarcinoma. To understand the molecular features of young and old adenocarcinoma patients, we investigated the expression level of a panel of miRNAs selected after a mini-literature review. The expression analysis was performed by the nCounter System® (NanoString Technologies) directly on RNA, including small RNAs. The analysis revealed that 7 miRNAs (miR-25-3p, miR-29c-3p, miR-33a-5p, miR-144-3p, miR-153-3p, miR-342-5p and miR-485-3p) were differentially expressed in the two groups (P<0.05). All of these miRNAs showed higher expression levels in young compared to old patients, and their predicted targets included EGFR, MET, VEGF-A, TP53 and PDGFRa. miR-144-3p had an opposite influence on overall survival since its upregulation was associated with a worse prognosis in young patients (P=0.01) and with a better outcome in the older group (P=0.03). We observed that lung cancer in young and old patients may be influenced by different regulatory mechanisms. Moreover, one of the down-regulated miRNAs showed a different prognostic impact in the two groups, confirming that young and old patients deserve a specific clinical approach.

The role of intracavitary therapies in the treatment of malignant pleural mesothelioma.

Surgery is one of the steps of multimodality approach for the treatment of MPM. Due to anatomical features, microscopically radical (R0) resection is never possible and a Macroscopic Complete Resection (R1) is considered the target for mesothelioma surgeons. Recently, intracavitary therapies have been described with the aim of extending the loco-regional effect of surgery. Different agents might be administered intrapleurally: chemotherapy drugs are the most widely used, but also photodynamic therapy (PDT) showed to lead to satisfactory long-term outcomes; furthermore, immunotherapies and gene therapies have been also reported. Despite promising results, no high-quality evidences are currently available and controlled randomized trials are required to establish the exact role of intracavitary therapies and to standardize the technique.

Is left upper lobectomy always worthwhile for early stage lung cancer? A comparison between left upper lobectomy, trisegmentectomy, and lingulectomy.

BACKGROUND AND OBJECTIVES: Lobectomy is the gold standard treatment for resectable Non-Small Cell Lung Cancer (NSCLC). We compared oncological outcomes of patients undergoing a "multi-segmentectomy" (trisegmentectomy or lingulectomy) and left upper lobectomy for early stage (T1-2, N0) NSCLC of the left upper lobe. METHODS: We retrospectively analyzed all patients with pathological early stage (T1-T2 N0) NSCLC located in left upper lobe who underwent a lobectomy, a trisegmentectomy, or a lingulectomy between 2006 and 2013, focusing on surgical and oncological outcomes. RESULTS: Among 159 patients, 105 patients underwent a lobectomy and 54 patients a multi-segmentectomy (33 lingulectomy and 21 trisegmentectomy). Actuarial mean Overall Survival was 87 months (95%CI 79-95) and 89 months (95%CI 76-101) for lobectomies and multi-segmentectomies, respectively (P-value: 0.895), while actuarial mean Disease Free Interval was 91 months (95%CI 82-100) and 96 months (95%CI 84-108) respectively (P-value: 0.565). We did not observe any difference in terms of local recurrence rate between the two groups (P = 0.337). CONCLUSIONS: Lingulectomy and trisegmentectomy lead to similar oncological outcomes compared to left upper lobectomy for T1 and T2 N0 NSCLC, and they could be used as an alternative to lobectomy even in patients with a good pulmonary function.

Diaphragm and lung-preserving surgery with hyperthermic chemotherapy for malignant pleural mesothelioma: A 10-year experience.

BACKGROUND: The best surgical treatment for malignant pleural mesothelioma is still under a debate, but recent evidence points toward a less-invasive approach to reduce morbidity and mortality. We reported our 10-year experience of a limited surgical approach associated with hyperthermic intrathoracic chemotherapy (HITHOC). MATERIAL AND METHODS: Between 2005 and 2014, patients with epithelioid or biphasic malignant pleural mesothelioma were treated with lung-diaphragm-pericardium-sparing pleurectomy associated with double-drug HITHOC; at least 3 cycles of adjuvant chemotherapy were then administered. The primary outcome examined was the feasibility of the procedure, whereas secondary outcomes were overall survival and disease-free interval. RESULTS: Among 49 patients, 41 were male. Median age was 68 years (35-76 years). Histology was epithelioid in 43 cases. Pathologic stage I, II, III, and IV occurred in 12, 14, 20, and 3 cases, respectively. No intraoperative complications or postoperative mortality occurred, whereas morbidity rate was 46.9%. Median hospital stay was 8 days (5-45 days). Actuarial median overall survival was 22 months and a 1-, 2-, and 5-year survival accounted for 79.6%, 45.7%, and 9.9%, respectively. Disease-free survival after surgery was 62%, 37.5%, and 18.5% at 1, 2, and 5 years, respectively. Risk factors analysis for overall survival confirmed a significant role for early stages, epithelioid histology, and fibrinogen serum levels. CONCLUSIONS: Cytoreductive surgery associated with HITHOC and adjuvant chemotherapy appears feasible and safe, with no mortality and low morbidity. Preserving lung and diaphragmatic function might warrant an acceptable long-term outcome.

The thymidylate synthase enhancer region (TSER) polymorphism increases the risk of thymic lymphoid hyperplasia in patients with Myasthenia Gravis.

BACKGROUND: Myasthenia Gravis (MG) is caused, in approximately 80% of the patients, by autoantibodies against the nicotinic acetylcholine receptor (AChR). The disease is often associated with pathological changes of the thymus: thymic epithelial tumours are present in about 10-20% of the patients, while up to 80% of the patients with early disease onset have thymic hyperplasia. Folate metabolism is required for the production of DNA precursors and for proper DNA methylation reactions, and impaired folate metabolism has been often associated with cellular growth and cancer. METHODS: We investigated if major polymorphisms of folate-related genes, namely MTHFR c.677C>T, MTR c.2756A>G, MTRR c.66A>G and TYMS TSER (a 28-bp tandem repeat in the 5' promoter enhancer region of TYMS) increase the risk of pathological changes of the thymus in AChR+ MG patients. A total of 526 AChR+ MG patients, including 132 patients with normal (involuted) thymus, 146 patients with thymic hyperplasia, and 248 patients with a thymoma were included in the study. Allele and genotype comparisons were performed among the three study groups, after correcting for multiple testing. RESULTS: The frequency of the TYMS TSER 3R allele was significantly higher in MG patients with thymic hyperplasia (P=0.004), and the TYMS TSER 3R3R genotype was significantly associated with increased risk of thymic hyperplasia [OR 2.71 (95% CI: 1.34-5.47)]. CONCLUSIONS: The 3R allele in the thymidylate synthase promoter enhancer region results in increased protein production, required for the synthesis of DNA precursors. The present study suggests that the TYMS TSER 3R allele increases the risk of thymic lymphoid hyperplasia in AChR+ MG patients.

Role of microRNA-33a in regulating the expression of PD-1 in lung adenocarcinoma.

BACKGROUND: MiRNAs are vital in functioning as either oncogenes or tumor suppressors in the cell cycle. Target transcripts for immune checkpoint molecules such as PD-1/PD-L1 and (programmed cell death-1/its ligand and cytotoxic T-lymphocyte antigen 4) have proven to be beneficial against several solid tumors, including lung adenocarcinoma. METHODS: Simultaneous quantification of the expression level of miR-33a and PD-1, PD-L1 and CTLA4 mRNAs with NanoString technology was performed in 88 lung adenocarcinoma specimens. A cohort of 323 lung adenocarcinoma patients from the cancer genome atlas (TCGA) database was further analyzed, in order to test our hypothesis. Potential interference of PD-1, PD-L1 and CTLA4 gene expression by miR-33a was predicted using the microRNA target prediction program RNA22. RESULTS: High miR-33a expression was significantly associated with younger (p = 0.005), female (p = 0.04), patients with low grade (p < 0.0001), early stage (p = 0.03) tumors, and better survival. The hypothesis of the involvement of miR-33a in PD-1/PD-L1/CTLA4 mechanisms was corroborated by the finding of putative miR-33a binding sites in all three genes using the RNA22 method. We found an inverse correlation between miR-33a and PD-1 levels (p = 0.01), as well as for PD-L1 (p = 0.01) and CTLA4 (p = 0.03) expression, and a significant better prognosis for patients with high miR-33a/low PD-1. TCGA database analysis confirmed that miR-33a high levels were associated with low PD-1 expression and with longer survival on a larger population. CONCLUSIONS: Our study emphasizes the notion of a potential value of miR-33a as a favorable prognostic marker through PD-1 regulation.

Intrathoracic solitary fibrous tumor - an international multicenter study on clinical outcome and novel circulating biomarkers.

Intrathoracic solitary fibrous tumor (SFT) is a rare disease. Radical resection is the standard of care. However, estimating prognosis and planning follow-up and treatment strategies remains challenging. Data were retrospectively collected by five international centers to explore outcome and biomarkers for predicting event-free-survival (EFS). 125 histological proven SFT patients (74 female; 59.2%; 104 benign; 83.2%) were analyzed. The one-, three-, five- and ten-year EFS after curative-intent surgery was 98%, 90%, 77% and 67%, respectively. Patients age (≥59 vs. <59 years hazard ratio (HR) 4.23, 95 confidence interval (CI) 1.56-11.47, p = 0.005), tumor-dignity (malignant vs. benign HR 6.98, CI 3.01-16.20, p <0.001), tumor-size (>10 cm vs. ≤10 cm HR 2.53, CI 1.10-5.83, p = 0.030), de Perrot staging (late vs. early HR 3.85, CI 1.65-8.98, p = 0.002) and resection margins (positive vs. negative HR 4.17, CI 1.15-15.17, p = 0,030) were associated with EFS. Furthermore, fibrinogen (elevated vs. normal HR 4.00, CI 1.49-10.72, p = 0.006) and the neutrophil-to-lymphocyte-ratio (NLR > 5 vs. < 5 HR 3.91, CI 1.40-10.89, p = 0.009) were prognostic after univariate analyses. After multivariate analyses tumor-dignity and fibrinogen remained as independent prognosticators. Besides validating the role of age, tumor-dignity, tumor-size, stage and resection margins, we identified for the first time inflammatory markers as prognosticators in SFT.

Prognostic role of TPL2 in early­stage non­small cell lung cancer.

Non­small cell lung cancer (NSCLC) accounts for ~70% of all lung cancer­associated mortalities worldwide. The serine/threonine protein kinase tumor progression locus 2 [TPL2/MAP3 kinase 8 (MAP3K8)] may impact oncogenic events; however the role of TPL2 in lung carcinogenesis remains unclear. The present study was focused on the potential prognostic role of TPL2 in 101 patients with early­stage NSCLC. Since TPL2 is a potential target of miR­21, the association between TPL2 and miR­21 expression was also examined. TPL2 and miR­21 mRNA expression was quantified using reverse transcription quantitative polymerase chain reaction (RT­qPCR). TPL2 protein levels were evaluated by immunohistochemistry (IHC). The present study identified that the mRNA expression of TPL2 was low in 52/101 (51%) cases and high in 49/101 (49%) cases. IHC analysis of TPL2 protein expression often demonstrated identical mRNA results. No statistically significant associations were observed between the mRNA expression of TPL2 and the predominant clinicopathological characteristics of the patients with NSCLC, as well as identifying no association between TPL2 and miR­21. TPL2 mRNA expression was significantly higher in patients with NSCLC with good prognosis (disease­free interval P=0.009; overall survival P=0.024), when compared with those of poor prognosis. Focusing on the difference in mRNA expression of TPL2 among the adenocarcinomas in affected patients, TPL2 was more highly expressed in lepidic adenocarcinomas compared with in the other subtypes (P=0.012). The present study is the first examination, to the best of our knowledge, of TPL2 in early­stage NSCLC in relation to miR­21, and in different adenocarcinoma subtypes. Future studies must clarify the mechanism by which TPL2 is involved in lung carcinogenesis due to its important translational implications.

Serum mesothelin, osteopontin and vimentin: useful markers for clinical monitoring of malignant pleural mesothelioma.

INTRODUCTION: Malignant pleural mesothelioma (MPM) is a relatively rare tumor, with the epithelioid type occurring more frequently. Several biomarkers have been suggested for screening and early diagnosis of MPM. Currently, high levels of soluble mesothelin-related peptides (SMRP), plasma osteopontin (pOPN) and vimentin have been reported in patients with MPM as promising markers for diagnosis, but their clinical use in monitoring is still discussed. The aim of our study was to evaluate the usefulness of these substances as markers of the clinical response to treatment in patients suffering from epithelioid mesothelioma. METHODS: 219 serum samples from 56 patients were collected during follow-up and the clinical response to therapy was recorded. Percentage differences between 2 consecutive measurements of SMRP, osteopontin and vimentin (Δ markers) by means of commercially available kits were correlated with changes in the clinical course. RESULTS: Δ SMRP, Δ pOPN and Δ vimentin showed statistically significant differences between the disease categories stable disease, partial response and disease progression (p = 0.0001, p = 0.035 and p = 0.0025 for SMRP, pOPN and vimentin, respectively). Moreover, contingency table analysis showed statistically significant differences between clinical response and Δ of each marker clustered into 3 groups (<-20%, between -20% and +20%, >+20%). CONCLUSIONS: The time course of Δ SMRP and Δ vimentin was strongly associated with disease status, and so was the time course of pOPN, albeit to a lesser extent. These markers appear to be particularly effective in cases of partial response and disease progression, while their possible use in stable disease should be better investigated.

Malignant pleural mesothelioma and mesothelial hyperplasia: A new molecular tool for the differential diagnosis.

Malignant pleural mesothelioma (MPM) is a rare asbestos related cancer, aggressive and unresponsive to therapies. Histological examination of pleural lesions is the gold standard of MPM diagnosis, although it is sometimes hard to discriminate the epithelioid type of MPM from benign mesothelial hyperplasia (MH).This work aims to define a new molecular tool for the differential diagnosis of MPM, using the expression profile of 117 genes deregulated in this tumour.The gene expression analysis was performed by nanoString System on tumour tissues from 36 epithelioid MPM and 17 MH patients, and on 14 mesothelial pleural samples analysed in a blind way. Data analysis included raw nanoString data normalization, unsupervised cluster analysis by Pearson correlation, non-parametric Mann Whitney U-test and molecular classification by the Uncorrelated Shrunken Centroid (USC) Algorithm.The Mann-Whitney U-test found 35 genes upregulated and 31 downregulated in MPM. The unsupervised cluster analysis revealed two clusters, one composed only of MPM and one only of MH samples, thus revealing class-specific gene profiles. The Uncorrelated Shrunken Centroid algorithm identified two classifiers, one including 22 genes and the other 40 genes, able to properly classify all the samples as benign or malignant using gene expression data; both classifiers were also able to correctly determine, in a blind analysis, the diagnostic categories of all the 14 unknown samples.In conclusion we delineated a diagnostic tool combining molecular data (gene expression) and computational analysis (USC algorithm), which can be applied in the clinical practice for the differential diagnosis of MPM.

Gene-Specific Methylation Analysis in Thymomas of Patients with Myasthenia Gravis.

Thymomas are uncommon neoplasms that arise from epithelial cells of the thymus and are often associated with myasthenia gravis (MG), an autoimmune disease characterized by autoantibodies directed to different targets at the neuromuscular junction. Little is known, however, concerning epigenetic changes occurring in thymomas from MG individuals. To further address this issue, we analyzed DNA methylation levels of genes involved in one-carbon metabolism (MTHFR) and DNA methylation (DNMT1, DNMT3A, and DNMT3B) in blood, tumor tissue, and healthy thymic epithelial cells from MG patients that underwent a surgical resection of a thymic neoplasm. For the analyses we applied the methylation-sensitive high-resolution melting technique. Both MTHFR and DNMT3A promoters showed significantly higher methylation in tumor tissue with respect to blood, and MTHFR also showed significantly higher methylation levels in tumor tissue respect to healthy adjacent thymic epithelial cells. Both DNMT1 and DNMT3B promoter regions were mostly hypomethylated in all the investigated tissues. The present study suggests that MTHFR methylation is increased in thymomas obtained from MG patients; furthermore, some degrees of methylation of the DNMT3A gene were observed in thymic tissue with respect to blood.

Chest wall resection for mesothelioma recurrence after surgery.

Malignant pleural mesothelioma is an aggressive and usually fatal disease, and its optimal management is still under debate. Surgery for recurrent malignant mesothelioma has been reported rarely in highly selected cases. We report a case of chest wall resection for local recurrence of epithelioid mesothelioma 3 years after cytoreductive surgery. Our patient experienced a 6-month disease-free survival after redo surgery, with complete resolution of his chest pain and discomfort.

EGFR and KRAS mutational analysis in a large series of Italian non-small cell lung cancer patients: 2,387 cases from a single center.

Activating EGFR mutations are important genetic alterations that have strong therapeutic implications for non-small cell lung cancer (NSCLC) patients. However, the role of KRAS mutations in this process is still under evaluation. Here, we report on the feasibility of a large­scale EGFR and KRAS mutation analysis in the daily routine of a single center. NSCLCs from 2,387 patients were screened for EGFR and KRAS mutations from January 2010 to September 2015. Mutational analyses were performed in a single laboratory using single strand conformation polymorphism (SSCP)-Sanger sequencing and matrix­assisted laser desorption ionization­time of flight (MALDI­TOF) on Sequenom platform for EGFR and pyrosequencing for KRAS. Activating EGFR mutations were found in 14.1% of all tumors, whereas KRAS mutations were found in 30.5% of all tumors. Direct sequencing showed analyzable cytological, small biopsy and surgical specimen percentages of 90.3, 90.9 and 98.1%, respectively, whereas the MALDI­TOF platform showed analyzable cytological samples, small biopsies and surgical specimens percentages of 94.6, 95.7 and 96.9%, respectively. The mean analytical turnaround times (TAT) were 4 and 3 days for direct sequencing and the MALDI­TOF platform, respectively. Our results confirm that small biopsy or cytological samples can be used for reliable EGFR and KRAS mutation testing and indicate that adopting the MALDI­TOF platform reduces the rate of missed samples among the samples. Moreover, the 3-day analytical TAT of the MALDI-TOF multi-target technique is appropriate for clinical management and reduces the overall treatment decision time.

Long-term results of percutaneous radiofrequency ablation of pulmonary metastases: a single institution experience.

OBJECTIVES: Surgical resection of pulmonary metastases is considered as a therapeutic procedure in selected cases. However, many patients are unable to tolerate surgical intervention due to comorbidities and/or poor pulmonary reserve, also related to repeated parenchymal resections. Considering this scenario, we decided to investigate the role of radiofrequency ablation (RFA). METHODS: The outcomes of all patients that underwent RFA for lung metastases, during the period 2003-2013, were analysed. The primary end-points were overall survival (OS) and local progression-free survival (LPFS). Secondary end-point was the analysis of possible risk factors affecting OS and LPFS. RESULTS: Ninety-nine RFAs were performed on 61 patients (38 men, 23 women, median age of 74 years). Fourteen patients were treated for two or more lesions, for a total of 86 lesions. Twelve lesions were treated up to three times. The median lesion diameter was 2 cm. The majority of patients were affected by lung metastases from colorectal cancer (47.5%). All procedures were successfully completed. One death occurred, whereas the morbidity rate was 11% (8% pneumothorax requiring chest drainage). At a median follow-up of 28 months, the 1-, 3-, 5-year OS (LPFS) rates were 94.8% (86.3%), 49.0% (70.3%) and 44.5% (68.3%), respectively. No significant correlation was found, using univariate and multivariate analysis, between OS and age, gender, histology of primary cancer (colon versus others), type of approach (computed tomography versus ultrasonography guidance), number of treated lesions (1 vs >1), disease-free interval (from primary tumour to first lung metastases) (1-35 vs >35 months), previous lung resections (yes versus no), whereas a tendency towards better OS was observed, by applying univariate analysis, for a lesion of <3 cm (P = 0.051) and for the presence of local disease 1 month after treatment (P = 0.056), however, without a statistically significant difference. With regard to LPFS, lesion dimensions (P = 0.005) and the presence of local disease 1 month after treatment (P < 0.001) were found to be significant risk factors, in both univariate and multivariate analyses. CONCLUSIONS: RFA appears as a feasible and safe procedure, with an acceptable morbidity, offering the possibility to safely repeat the treatment on the same lesion. RFA can be considered a valid option for the local control of lung metastases, in patients not eligible for surgery, especially those with lesions smaller than 3 cm.

Induction therapy followed by surgical resection in Stage-III thimic epithelial tumors: Long-term results from a multicentre analysis of 108 cases.

INTRODUCTION: So far no specific oncological strategies have been validated for locally-advanced epithelial thymic tumors (TETs). We herein report the long-term results of a large multicentric experience adopting a multimodal treatment. METHODS: From 01/1990 to 12/2010, the clinical data of 108 Masaoka Stage-III TETs patients surgically treated after induction therapy (IT) were retrospectively reviewed. Different IT-regimens were administered: ADOC (32 pts); PAC (38 pts); CEE (38 pts). Radiotherapy was concurrently used in 5 patients only. The end-points of the study were the evaluation of: (1) resectability; (2) overall long-term survival (LTS) and disease-free survival (DFS); and (3) independent prognostic factors. The Mann-Whitney and Fisher's exact tests were applied to test the associations. Survival analysis was performed by the Kaplan-Meier method and log-rank test. RESULTS: Mean age and male/female ratio were 51 ± 13 years and 61/47, respectively. World Health Organization (WHO) histotype was: A in 6 pts (5.6%), AB in 18 (16.7%), B1 in 15 (13.9%), B2 in 26 (24.1%), B3 in 23 (21.3%), and thymic carcinoma in 20 (18.5%). Thirty-day mortality was 1.8%. A total of 81 (75%) had R0-resection, 11 (10.2%) R1 and 16 (14.8%) R2-resection. Adjuvant therapy was performed in 71 patients. During the follow-up a relapse of disease was observed in 38 pts(35.2%). Five-years DFS and LTS were 69.3% and 79.3%, respectively. At univariate analysis, WHO-type B3/C ("high-risk") TETs (p=0.001) and recurrence of disease (p=0.02) were predictors of poor LTS while only a slight correlation was found for R-status and "CHT-regimen type" (p=0.097 and p=0.067, respectively). At multivariate analysis WHO "high-risk" TETs (H.R.5.73;C.I.:1.77-18.57) and ADOC-regimen (H.R.2.84;C.I.:1.37-5.86) were independent predictors of poor survival. CONCLUSIONS: A multimodal treatment for Stage-III thymic tumors may achieve a rewarding survival. WHO-Histology seems to be the most important prognostic factor.

Minimally invasive mediastinal surgery.

In the past, mediastinal surgery was associated with the necessity of a maximum exposure, which was accomplished through various approaches. In the early 1990s, many surgical fields, including thoracic surgery, observed the development of minimally invasive techniques. These included video-assisted thoracic surgery (VATS), which confers clear advantages over an open approach, such as less trauma, short hospital stay, increased cosmetic results and preservation of lung function. However, VATS is associated with several disadvantages. For this reason, it is not routinely performed for resection of mediastinal mass lesions, especially those located in the anterior mediastinum, a tiny and remote space that contains vital structures at risk of injury. Robotic systems can overcome the limits of VATS, offering three-dimensional (3D) vision and wristed instrumentations, and are being increasingly used. With regards to thymectomy for myasthenia gravis (MG), unilateral and bilateral VATS approaches have demonstrated good long-term neurologic results with low complication rates. Nevertheless, some authors still advocate the necessity of maximum exposure, especially when considering the distribution of normal and ectopic thymic tissue. In recent studies, the robotic approach has shown to provide similar neurological outcomes when compared to transsternal and VATS approaches, and is associated with a low morbidity. Importantly, through a unilateral robotic technique, it is possible to dissect and remove at least the same amount of mediastinal fat tissue. Preliminary results on early-stage thymomatous disease indicated that minimally invasive approaches are safe and feasible, with a low rate of pleural recurrence, underlining the necessity of a "no-touch" technique. However, especially for thymomatous disease characterized by an indolent nature, further studies with long follow-up period are necessary in order to assess oncologic and neurologic results through minimally invasive approaches. Furthermore, increased robotic experience and studies, including randomized controlled trials, are needed to validate the findings of the current literature.