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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.

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Simple Summary Thymic epithelial tumours are rare and insidious malignancies. Histologically, they can be divided into different WHO subtypes and relapse risk classes. Pre-treatment biopsy is not always feasible or accurate in distinguishing WHO classes. (18)FDG PET/CT scan has been reported to play a remarkable role in the prediction of histology in these tumours (the so-called "non-invasive biopsy"). The present narrative review would like to summarise current evidence on this topic and discuss potential applications. Background: The usefulness of (18)FDG PET/CT scan in the evaluation of thymic epithelial tumours (TETs) has been reported by several authors, but data are still limited and its application in clinical practice is far from being defined. Methods: We performed a narrative review of pertinent literature in order to clarify the role of (18)FDG PET/CT in the prediction of TET histology and to discuss clinical implications and future perspectives. Results: There is only little evidence that (18)FDG PET/CT scan may distinguish thymic hyperplasia from thymic epithelial tumours. On the other hand, it seems to discriminate well thymomas from carcinomas and, even more, to predict the grade of malignancy (WHO classes). To this end, SUVmax and other PET variables (i.e., the ratio between SUVmax and tumour dimensions) have been adopted, with good results. Finally, however promising, the future of PET/CT and theranostics in TETs is far from being defined; more robust analysis of imaging texture on thymic neoplasms, as well as new exploratory studies with "stromal PET tracers," are ongoing. Conclusions: PET may play a role in predicting histology in TETs and help physicians in the management of these insidious malignancies.

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Alveolo-pleural fistula remains a serious post-operative complication in lung cancer patients after surgery, which is associated with prolonged hospital stay and higher healthcare costs. The aim of this study is to evaluate the efficacy of a polyglycol acid (PGA)-sheet known as Neoveil in preventing post-operative air-leak in cases of detected intra-operative air-leak after lung resection. Between 11/2021 and 7/2022, a total of 329 non-small cell lung cancer (NSCLC) patients were surgically treated in two institutions. Major lung resections were performed in 251 cases. Among them, 44 patients with significant intra-operative air-leak at surgery were treated by reinforcing staple lines with Neoveil (study group). On the other hand, a historical group (selected by propensity score matched analysis) consisting of 44 lung cancer patients with significant intra-operative air leak treated by methods other than the application of sealant patches were considered as the control group. The presence of prolonged air-leak (primary endpoint), pleural drainage duration, hospital stay, and post-operative complication rates were evaluated. The results showed that prolonged air-leak (>5 days after surgery) was not observed in study group, while this event occurred in four patients (9.1%) in the control group. Additionally, a substantial reduction (despite not statistically significant) in the chest tube removal was noted in the study group with respect to the control group (3.5 vs. 4.5, p = 0.189). In addition, a significant decrease in hospital stay (4 vs. 6 days, p = 0.045) and a reduction in post-operative complications (2 vs. 10, p = 0.015) were observed in the study group when compared with the control group. Therefore, in cases associated with intra-operative air-leak after major lung resection, Neoveil was considered a safer and more effective aerostatic tool and represents a viable option during surgical procedures.

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BackgroundAlthough the feasibility and safety of Uniportal-Video-Assisted thoracic surgery (U-VATS) has been proven, its surgical effectiveness is still debated. The aim of this study is to assess the equivalence of the U-VATS approach compared with an open technique in terms of surgical (nodal-upstaging, complications, and post-operative results) and short-term survival outcomes. MethodsThe clinical data of patients undergoing lobectomy for NSCLC at our center, from January 2014 to December 2019, were analyzed retrospectively. All patients undergoing open or U-VATS lobectomy with lymphadenectomy for early-stage lung cancer (cT1-T3N0, stages IA-IIB) were included in the study. Only 230 patients satisfied the inclusion criteria. Group bias was reduced through 1:1 propensity score matching, which resulted in 46 patients in each group (open surgery and U-VATS). ResultsThe intra- and post-operative mortality were null in both groups. There was no difference in the post-operative complications (p: 1.00) between U-VATS and open lobectomy. There was also no recorded difference in the pathological nodal up-staging [11 (23.9%) after thoracotomy vs. 8 (17.4%) after U-VATS, p: 0.440). The chest tube duration was longer in the open group (p: 0.025), with a higher post-operative pain (p: 0.001). Additionally, the 3-year overall survival (OS) was 78% after U-VATS lobectomy vs. 74% after open lobectomy (p: 0.204), while 3-year disease-specific survival (DSS) was 97 vs. 89% (p: 0.371), respectively. The 3-year disease-free survival (DFS) was 62% in the U-VATS group and 66% in the thoracotomy group, respectively (p: 0.917). ConclusionsUniportal-VATS lobectomy for the treatment of early-stage lung cancer seems to be a safe and effective technique with similar surgical and short-term survival outcomes as open surgery, but with lower post-operative pain and shorter in-hospital stay.

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Background: A prognostic score including T-dimension, age, histology and lymph node ratio was previously proposed in absence of an external validation dataset. The aim of the current study was to validate the proposed prognostic score using an independent dataset. Methods: Data of patients with lung carcinoids, who underwent surgical resection and lymphadenectomy in five institutions from 1 January 2005 to 31 December 2019, were retrospectively analyzed. Two risk groups were created based on the following data: age, histology, node ratio and pT for disease-free survival (DFS); age, sex, node ratio and pT for overall survival (OS). The previously proposed score was validated, identifying two groups of patients: a high risk (HRG) and low risk (LRG) group. Results: The final analysis was conducted on 283 patients. Regarding DFS, 230 (81.3%) patients were assigned to the LRG and 53 (18.7%) to the HRG. Considering OS, 268 (94.7%) were allocated in the LRG and 15 (5.3%) in the HRG. The 5-year DFS was 92.7% in the LRG vs. 67% in the HRG (p < 0.001) while the 5-year OS was 93.6% in the LRG vs. 86.2% in the HRG (p = 0.29) with clear curve separation. Conclusion: Our analysis confirmed the validity of the composite score for DFS in lung carcinoids. Regarding OS, statistical significance was not reached because of a low number of deaths and patients in the HRG.

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.

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Background: Outcomes for locally advanced NSCLC with pathological complete response (pCR), i.e., pT0N0 after induction chemoradiotherapy (IT), have been seldom investigated. Herein, long-term results, in this highly selected group of patients, have been evaluated with the aim to identify prognostic predictive factors. Methods: Patients affected by locally advanced NSCLC (cT1-T4/N0-2/M0) who underwent IT, possibly following surgery, from January 1992 to December 2019, were considered for this retrospective analysis. Survival rates and prognostic factors have been studied with Kaplan-Meier analysis, log-rank and Cox regression analysis. Results: Three-hundred and forty-three consecutive patients underwent IT in the considered period. Out of them, 279 were addressed to surgery; among them, pCR has been observed in 62 patients (18% of the total and 22% of the operated patients). In the pCR-group, clinical staging was IIb in 3 (5%) patients, IIIa in 28 (45%) patients and IIIb in 31 (50%). Surgery consisted of (bi)lobectomy in the majority of cases (80.7%), followed by pneumonectomy (19.3%). Adjuvant therapy was administered in 33 (53.2%) patients. Five-year overall survival and disease-free survival have been respectively 56.18% and 48.84%. The relative risk of death, observed with the Cox regression analysis, was 4.4 times higher (95% confidence interval (CI): 1.632–11.695, p = 0.03) for patients with N2 multi-station disease, 2.6 times higher (95% CI: 1.066–6.407, p = 0.036) for patients treated with pneumonectomy and 3 times higher (95% CI: 1.302–6.809, p = 0.01) for patients who did not receive adjuvant therapy. Conclusions: Rewarding long-term results could be expected in locally advanced NSCLC patients with pCR after IT followed by surgery. Baseline N2 single-station disease and adjuvant therapy after surgery seem to be associated with better prognosis, while pneumonectomy is associated with poorer outcomes.

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