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BackgroundThe role of the number of involved structures (NIS) in thymic epithelial tumors (TETs) has been investigated for inclusion in future staging systems, but large cohort results still are missing. This study aimed to analyze the prognostic role of NIS for patients included in the European Society of Thoracic Surgeons (ESTS) thymic database who underwent surgical resection.MethodsClinical and pathologic data of patients from the ESTS thymic database who underwent surgery for TET from January 2000 to July 2019 with infiltration of surrounding structures were reviewed and analyzed. Patients' clinical data, tumor characteristics, and NIS were collected and correlated with CSS using Kaplan-Meier curves. The log-rank test was used to assess differences between subgroups. A multivariable model was built using logistic regression analysis.ResultsThe final analysis was performed on 303 patients. Histology showed thymoma for 216 patients (71.3%) and NET/thymic carcinoma [TC]) for 87 patients (28.7%). The most frequently infiltrated structures were the pleura (198 cases, 65.3%) and the pericardium in (185 cases, 61.1%), whereas lung was involved in 96 cases (31.7%), great vessels in 74 cases (24.4%), and the phrenic nerve in 31 cases (10.2%). Multiple structures (range, 2-7) were involved in 183 cases (60.4%). Recurrence resulted in the death of 46 patients. The CSS mortality rate was 89% at 5 years and 82% at 10 years. In the univariable analysis, the favorable prognostic factors were neoadjuvant therapy, Masaoka stage 3, absence of metastases, absence of myasthenia gravis, complete resection, thymoma histology, and no more than two NIS. Patients with more than two NIS presented with a significantly worse CSS than patients with no more than two NIS (CSS 5- and 10-year rates: 9.5% and 83.5% vs 93.2% and 91.2%, respectively; p = 0.04). The negative independent prognostic factors confirmed by the multivariable analysis were incomplete resection (hazard ratio [HR] 2.543; 9

Objectives: Aim of this study is to identify the factors that may influence the lymphadenectomy during VATS anatomical lung resection with particular interest on operator experience. Materials and methods: Clinical and pathological data from the prospective VATS Italian nationwide registry were reviewed and analysed. Patients with incomplete data regarding tumor and surgical characteristics, GGO, or with distant metastases were excluded. Patients clinical data, tumor characteristics, operation information and surgeon experience were collected and compared to resected lymph nodes number (#RN), resected N2 nodes number (#N2RN) and resected N2 stations number. A multivariable model was built using logistic regression analysis. Surgeon experience was categorized considering the number of VATS major anatomical resection and years after residency. Results: The final analysis was conducted on 3727 patients. The median #RN and #N2RN were 11 (1-51) and 5 (0-41). Regarding the analysed outcomes, #N2RN > 6 resulted in 1812 (48.8%)cases, #RN > 10 in 2124 (57.0%)cases and more than 3 N2 stations were harvested in 1447 (38.8%)patients. First operator experience with number of VATS lobectomies>50 (p < 0.001), operator seniority after residency5-10years (p < 0.001), cTNM II/III(p = 0.017), lobectomy/bilobectomy vs segmentectomy (p < 0.001), and upper/middle lobe tumor location (p < 0.005)resulted significantly associated to #N2RN > 6 at the multivariable analysis. First operator experience with number of VATS lobectomies>50 (p < 0.001), operator seniority after residency5-10years (p < 0.001) and lobectomy/bilobectomy (p < 0.001) resulted significantly associated to #RN > 10 at the multivariable analysis. Conclusions: Our study showed that lymphadenectomy during VATS lobectomy is influenced by tumor factors such as c

Background: The prognostic difference among patients affected by NSCLC with hilar metastases only or mediastinal nodes metastases without hilar involvement (skip metastases) is still unclear. Aim of this study is to analyse if prognostic difference are present or if the two groups present the same survival outcome. Materials and methods: Data on NSCLC patients from 7 high volume centres (2004-2014) were collected and retrospectively reviewed. Histology different from adenocarcinoma(ADC) or squamous cell carcinoma(SCC), patients without data on lymphadenectomy, who underwent neoadjuvant treatment, with distant metastases or incomplete resection were excluded, selecting patients with hilar involvement or with skip metastases. Different prognostic factors such as Tstage, histology, pathological stage, nodal characteristics and adjuvant therapy administration were correlated to overall survival (OS) by the Kaplan-Meier product-limit method. The log-rank test was used to assess differences between subgroups. A multivariable Cox proportional hazard model was developed using stepwise regression to compare the prognostic power of different factors. Results: The final analysis was conducted on 480 adenocarcinoma/squamous cell carcinoma patients. Five-year OS (5YOS) resulted 53.9%. No significant differences in OS were detected comparing pN1 vs. pN2 patients or stage IIB vs. stage IIIA-B patients. Univariable confirmed as favourable prognostic factors young age (P<.001), T1-2 tumors (P=.030), number of resected nodes≥10 (P=.040), lymph node ratio (P=.026). Multivariable analysis confirmed as independent negative prognostic factors T≥3 (HR:1.385, 95%CI:1.037-1.851, P=.027) and age≥68 years (HR1.637, 95%CI:1.245-2.152). Conclusion: Patients with N1 involvement or skip metastases present a similar prognosis, suggesting that N2 involvement in these cases may be related to a direct lymphatic drainage to the mediastinal stations.

Background The incidence of synchronous multiple primary lung cancer (SMPLC) has progressively increased, due to recent advances in imaging. To date, no guidelines defining recommendations for patients' selection and no standard treatment of cases with SMPLC have been defined. The primary aim of this systematic review was to assess survival among patients treated with lobectomy or sublobar resection MPLC. Methods Comprehensive literature search of Medline, the Cochrane Library, reference lists, and ongoing studies was performed according to a prospectively registered design (PROSPERO: CRD42019115487). All studies published between 1998 and December 2020 that examined treatments with lobectomy compared to sublobar resection were included. Two double-blind investigators independently selected articles. Primary outcomes were to assess the 5-year overall survival (OS) rate among patients treated with lobectomy or sublobar resection and the impact of lymph node status on 5-year OS and 5-year disease-free survival in patients with MPLC. Results The search yielded 424 articles; 4 observational studies met the inclusion criteria and collectively evaluated 298 patients with a mean age ranging from 61.5 to 67 years. A total of 112 patients were treated for bilateral synchronous tumors and 186 patients for unilateral multiple synchronous tumors. All included studies showed that the type of resection, lobectomy or limited resection, had no significant impact on survival. Conclusion Limited resection is a valuable treatment option for MPLC. However, the clinical level of evidence of the studies found is low and randomized studies are needed to clarify the extent of resection in MPLC.

BackgroundDespite the lack of evidence-based on prospective randomized studies, surgery has become the cornerstone of the treatment in patients with pulmonary oligometastatic sarcomas. Our study aimed to construct a composite prognostic score for metachronous oligometastatic sarcoma patients. MethodsA retrospective analysis was performed on data patients who underwent radical surgery for metachronous metastases in six research institutes from January 2010 to December 2018. The log-hazard ratio (HR) obtained from the Cox model was used to derive weighting factors for a continuous prognostic index designed to identify differential outcome risks. ResultsA total of 251 patients were enrolled in the study. In the multivariate analysis, a longer disease-free interval (DFI) and a lower neutrophil-to-lymphocytes ratio (NLR) were predictive of a better overall survival (OS) and disease-free survival (DFS). A prognostic score was developed based on DFI and NLR data, identifying 2 risk class groups for DFS (3-years DFS 20.2% for the high-risk group [HRG]and 46.4% for the low-risk group [LRG] [<0.0001]) and 3 risk groups for OS (3 years OS 53.9% for the HRG vs. 76.9% for the intermediate-risk group and 100% of the LRG (p < 0.0001)). ConclusionThe proposed prognostic score effectively predicts outcomes for patients with lung metachronous oligo-metastases from the surgically treated sarcoma.

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Introduction: Stage Ia presents an optimal survival rate after surgical resection, but the type of lymphadenectomy to use in these patients is still debated. The aim of this study is evaluate if one type of lymphadenectomy adopted influences survival in patients who underwent VATS lobectomy for stage Ia NSCLC.Methods: Clinical and pathological data from pIa patients in the prospective VATS Italian nationwide registry were reviewed and analysed. Patients and tumour characteristics,type of lymphadenectomy (sampling or radical nodal dissection,MRLD), were collected and correlated to Overall Survival(OS) and Disease free Survival(DFS). The Kaplan-Meier product-limit method was used to estimate OS and DFS and the log-rank test was adopted to evaluate the differences between groups. A propensity match was performed to reduce bias due to the retrospective study design.Results: The final analysis was conducted on 2039 patients, 179 died during follow-up,recurrence rate was 13%. MRLD was performed in 1287(63.1%)patients. The univariable analysis identified as favourable prognostic factors for OS the female sex(p = 0.023), low ECOG-score(0.008),low SUVmax(p < 0.001), GGO appearance(p < 0.001), pT < 2 cm(p = 0.002) and low tumour grading(p = 0.002). The multivariable analysis confirmed as independent prognostic factors low ECOG-score(p = 0.012), low SUVmax(p < 0.001) and low tumour grading(p < 0.001). Analysing survival in patients with solid/sub-solid nodules and after propensity score matching for pTdimension and number of N2 resected lymphnodes, no OS differences were present comparing sampling vs MRLD.Conclusion: Survival in pIa patients seems to be determined by patient and tumour characteristics such as performance status,grading and SUVmax. Type of lymphadnectomy did not seem to be correlated with OS in these patients.

Objective To investigate risk factors for nodal upstaging in patients with lung carcinoids and to understand which type of lymphadenectomy is most appropriate. Methods Data regarding patients with lung carcinoids, who underwent surgical resection and lymphadenectomy in five institutions from January 1, 2005 to December 31, 2019, were collected and retrospectively analyzed. Clinical and pathological tumor characteristics were correlated to analyze lymph node upstaging. Results The analysis was conducted on 283 patients. Pathology showed 230 typical and 53 atypical carcinoids. Nodal and mediastinal upstaging occurred in 33 (11.6%) and 16 (5.6%) patients, respectively. At the univariable analysis, nodal upstaging was significantly correlated with central location (p = 0.003), atypical histology (p < 0.001), pT dimension (p = 0.004), and advanced age (p = 0.043). The multivariable analysis confirmed atypical histology (odds ratio [OR]: 11.030; 95% confidence interval [CI]: 4.837-25.153, p < 0.001) and central location (OR: 3.295; 95% CI: 1.440-7.540, p = 0.005) as independent prognostic factors for nodal upstaging. Atypical histology (p < 0.001), pT dimension (p = 0.036), number of harvested lymph node stations (p = 0.047), and type of lymphadenectomy (p < 0.001) correlated significantly with mediastinal upstaging. The multivariable analysis confirmed atypical histology (OR: 5.408; 95% CI: 1.391-21.020, p = 0.015) and pT (OR: 1.052; 95% CI: 1.021-1.084, p = 0.001) as independent prognostic factors. Conclusion Atypical histology, dimension, and central location are associated with a high-risk for occult hilo-mediastinal metastases, and mediastinal radical dissection may predict nodal upstaging. Thus, we suggest radical mediastinal lymph node dissection in high-risk tumors, reserving sampling, or lobe-specific dissection in peripheral, small typical carcinoids.

Objectives The study aimed to assess the feasibility of radical surgical treatment for selected bone-oligometastatic non-small cell lung cancer (NSCLC) patients and to identify prognostic factors associated with survival. Materials and methods The clinical records of 27 patients with bone synchronous oligometastatic NSCLC were retrospectively analyzed. Results Thirteen (48.1%) bone metastases were treated by surgery and 14 (51.9%) by local radiotherapy. Eighteen (66.7%) patients underwent induction chemotherapy before lung surgery, and 3 (11.1%) concurrent radiotherapy. Pulmonary surgery was a major lung resection in 23 (85.2%) cases. Intraoperative and 30-days mortality was null. Only one major (ARDS) and 10 (37.04%) mild complications (like air leakage, arrhythmia, and mucus retention) were recorded. 1-year and 5-years OS from the diagnosis and 1-year, 3- years disease-free survival (DFS) were 96%, 38%, and 66%, 30%, respectively. After stepwise Cox regression analysis, local recurrence (p = 0.05) and metachronous metastases (p = 0.04) maintained their independent prognostic value as overall survival negative determinants. Nodal upstaging (p = 0.04) and nonsurgical treatment of bone lesion (p = 0.03) turned out to be independent risk factors for shorter DFS; the vertebral localization of bone metastases showed only a remarkable trend towards significance (p = 0.06) as a risk factor for a worse DFS. Conclusions In selected patients, surgical treatment of primary NSCLC and bone synchronous metastasis seems to be safe and feasible and rewarding survivals may be expected.

Background: Thymic carcinoma is a rare and highly malignant tumor with a dismal prognosis, which occasionally coexists with myasthenia gravis (MG). This study aims to investigate the MG incidence on a surgical cohort of patients with thymic carcinoma and to explore its influence on long-term survival. Methods: the prospectively collected data from the ESTS database on thymic epithelial tumors were reviewed. Clinical, pathological, and survival information on thymic carcinoma were analyzed. Results: the analysis was conducted on 203 patients, with an equal gender distribution (96 males and 107 females). MG was detected in 22 (10.8%) patients, more frequently elderly (>60 years, p = 0.048) and male (p = 0.003). Induction therapy was performed in 22 (10.8%) cases. After surgery, 120 (59.1%) patients had a Masaoka stage II-III while complete resection (R0) was achieved in 158 (77.8%). Adjuvant therapy was performed in 68 cases. Mean follow-up was 60 (SD = 14) months. The 3-year, 5-year and 10-year survival rates were 79%, 75% and 63%, respectively. MG did not seem to influence long-term survival (5-year survival in non-MG-TCs 78% vs. 50% in MG-TCs, p = ns) as age < 60 years, female gender, early Masaoka stage, and postoperative radiotherapy did, conversely. Conclusions: myasthenia occurred in about 10% of thymic carcinomas and it did not seem to affect significantly the long-term prognosis in surgically treated thymic carcinoma-patients.

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Aims To explore the long-term survival in lung cancer patients with persistent mediastinal lymph nodal disease after neoadjuvant followed by surgical resection and to analyse prognostic factors in this specific subset of patients Background Surgery in non-small-cell lung cancer (NSCLC) patients with N2-disease after neoadjuvant therapy (NAD) has been debated and has been even more questioned with the advent of immunotherapy. Objective Describe long-term results of a multimodal approach in locally-advanced NSCLC patients with persistence of N2-disease and identify prognostic factors to target the strategy of care. Methods We retrospectively reviewed data of 121 consecutive Stage IIIA-N2 NSCLC patients who underwent NAD (chemoradiotherapy or chemotherapy) from 01/00 to 12/19, focusing our analysis on 37 patients with persistent N2s status after surgery. Kaplan-Meier and Cox regression analysis explored the associations between mortality and potential risk factors. Results The 5-year survival was 29.8%. Cox regression analysis suggested that young age (HR=0.98, C.I.95%: 0.97- 1.00; p=0.062), male sex (HR=3.8,C.I.95%:1.06-13.73;p=0.04), and adjuvant therapy (HR=6.81,C.I.95%:0.96-53.94;p=0.06) influenced long-term outcomes in these patients. Conclusion We herein observed suboptimal long-term results in this NSCLC patient subset, and, considering emerging results adopting immunotherapy following chemoradiotherapy, surgery should be carefully considered in very selected cases (young and clinically fit patients) and combined with adjuvant therapy after surgery.

Introduction To date, no validated predictors of response before neoadjuvant therapy (NAD) are currently available in locally advanced non-small-cell lung cancer (NSCLC). In this study, different peripheral blood markers were investigated before NAD (pre-NAD) and after NAD/before surgery (post-NAD) to evaluate their influence on the treatment outcomes. Methods Patients affected by locally advanced NSCLC (cT1-T4/N0-2/M0) who underwent NAD followed by surgery from January 1996 to December 2019 were considered for this retrospective analysis. The impact of peripheral blood markers on downstaging post-NAD and on overall survival (OS) was evaluated using multivariate logistic and Cox regression models. Time to event analysis was performed by means of Kaplan-Meier survival curves and Log Rank tests at 5 years from surgery. Results Two hundred and seventy-two consecutive patients were included. Most of the patients had Stage III NSCLC (83.5%). N2 disease was reported in 188 (69.1%) patients. Surgical resection was performed in patients with stable disease or downstaging post-NAD. Nodal downstaging was observed in 80% of clinical N2 (cN2) patients. The median follow-up of the total series was 74 months (range 6-302). Five-year OS in the overall population and in N2 population was 74.6% and 73.5%, respectively. The pre-surgery platelets level (PLT) (p = 0.019) and the variation (pre-NAD/post-NAD) of the neutrophil/lymphocyte ratio (p = 0.024) were identified as independent prognostic factors of OS. The preoperative PLT value (p value = 0.031) was confirmed as the only predictor of NAD response. Conclusions The clinical role of peripheral blood markers in locally advanced NSCLC needs to be further investigated. Based on these preliminary results, these factors may be used as auxiliary markers for the prediction of response to neoadjuvant treatment and as prognostic factors for stratification in multimodal approaches.

BACKGROUND: The aim of this study is to analyze the prognostic factors in patients that underwent induction therapy and surgery for clinical stage III NSCLC. METHODS: Clinical and pathological characteristics of stage III NSCLC patients for N2 involvement that underwent neoadjuvant treatment (NAD) and surgery from 1/01/1998 to 31/12/2017 were collected and retrospectively analyzed. Tumor characteristics, yClinical, yPathological stage and lymph node characteristics were correlated to Overall Survival (OS). RESULTS: The analysis was conducted on 180 patients. Five-year OS (5YOS) was 50.9%. Univariable analysis results revealed old age (p = 0.003), clinical N2 post-NAD (p = 0.01), pneumonectomy (0.005), persistent pathological N2 (p = 0.039, HR 1.9, 95% CI 1.09-2.68) and adjuvant therapy absence (p = 0.049) as significant negative prognostic factors. Multivariable analysis confirmed pN0N1 (p = 0.02, HR 0.29, 95% CI 0.13-0.62) as a favorable independent prognostic factor and adjuvant therapy absence (p = 0.012, HR 2.61, 95% CI 1.23-5.50) as a negative prognostic factor. Patients with persistent N2 presented a 5YOS of 35.3% vs. 55.8% in pN0N1 patients. Regarding lymph node parameters, the lymph node ratio (NR) significantly correlated with OS: 5YOS of 67.6% in patients with NR < 50% vs. 29.5% in NR > 50% (p = 0.029). CONCLUSION: Clinical response aided the stratification of prognosis in patients that underwent multimodal treatment for stage III NSCLC. Adjuvant therapy seemed to be an important option in these patients, while node ratio was a strong prognosticator in patients with persistent nodal involvement.

Objective Malignant mesothelioma (MM) is usually diagnosed by histological examination of tissue samples; however, effusion cytology offers an opportunity to identify a strong possibility for mesothelioma diagnosis at an early stage. We conducted a retrospective analysis of cytological specimens from a large series of histologically proven MM diagnosed over 19 years. The cases were reviewed and reclassified according to the International System for Reporting Serous Fluid Cytopathology (ISRSFC).Methods A total of 450 cases were identified. Cytological analysis was present in 210 patients (164 pleural and 46 peritoneal effusions). All cases were reviewed and reclassified according to the proposed ISRSFC scheme. A comparison among the cytomorphological features was made throughout the different diagnostic categories.Results The 210 cases were histologically diagnosed as follows: 192 (91.4%) cases had an epithelioid type and 18 (8.6%) had a sarcomatoid subtype of MM. The cytological cases were reclassified as follows: 2 (0.9%) as non-diagnostic (ND), 81 (38.6%) as negative for malignancy (NFM), 4 (1.9%) as atypia of undetermined significance (AUS), 11 (5.2%) as suspicious for malignancy (SFM), 112 (53.4%) as malignant (MAL). Sarcomatoid cells in the MAL category were characterised cytomorphologically by more pronounced discohesion. In comparison with the epithelioid subtype, the tumour cells appeared solitary with moderate or marked nuclear pleomorphism, and irregular chromatin.Conclusions It is important to recognise the cytological characteristics of this aggressive entity to suggest an early and precise possible diagnosis. Morphological features, coupled with clinico-radiological data may help the clinicians in adequately managing the patients.