F-024TIME-TREND ANALYSIS OF THE PULMONARY FUNCTION AFTER SURGICAL TREATMENT FOR OESOPHAGEAL CANCER: POTENTIALITY AND ROLE OF PULMONARY REHABILITATION

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Surgical treatment in patient with non-small-cell lung cancer with fissure involvement: Anatomical versus nonanatomical resection

OBJECTIVE: Despite the intense debate concerning the prognostic impact of fissure involvement (FI) in patients with non-small-cell lung cancer, no specific surgical strategies have been yet recommended when this condition occurs. In this setting, we report our monocentric 10-years experience to investigate this issue. METHODS: From January 2000 to January 2010, the clinical data of 40 non-small-cell lung cancer patients with FI undergoing curative resection were retrospectively reviewed. The sample was stratified according to the type of resection: group A (28 patients): anatomical resection (bilobectomy [21 patients], pneumonectomy [7 patients]); group B (12 patients): nonanatomical resection (lobectomy plus wedge resection [LWR]). The end-points were (1) impact of different surgical approach on the pulmonary function (measured before surgery and 1 month after discharge); (2) disease-specific survival; and (3) tumor recurrence.The t test, χ, and log-rank tests, Kaplan-Meier method, and Cox and logistic regression analyses were used for the statistical analysis. RESULTS: No differences between the two groups were found when comparing the clinical characteristics, histology, pN or pT status, p-stage, residual (R1) disease, tumor grading, or tumor size. Similarly, the baseline preoperative function (tested as forced expiratory volume in 1 second-%-predicted, FEV1%) was likewise comparable (92.5% ± 21.0% in group A versus 85.2% ± 20.0% in group B; p = not significant). The decline of FEV1% after surgery was slightly higher in group A (-24.9% ± 13.5%) when compared with that in group B (-19.5% ± 13.3%), but this difference was not statistically significant (p = ns). Nevertheless, the 5-year disease-specific survival was 56% for group A and 47% for group B (p = ns). The recurrence rate did not differ between the patients undergoing a LWR (3 of 12 patients) and those undergoing a bilobectomy or pneumonectomy (9 of 28 patients) (p = ns). The presence of FI extended for more than 3 cm was found to be the most significant prognostic factor when analyzing survival (p = 0.002) and recurrence rate (p< 0.001). CONCLUSIONS: Our results suggest that nonanatomical resection (LWR) could be considered as a feasible surgical option (especially in "frail" patients with an extent of FI less than 3 cm) in the light of the similar oncological and functional outcome compared with anatomical resection. Further studies based on larger series are needed to confirm these preliminary data and also to investigate the impact on the postoperative quality of life

post operative rehabilitation for surgically resected non small cell lung cancer patients serial pulmonary functional analysis

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Single center experience on talc poudrage morbidity: focus on high talc dosage

Malignant pleural effusion (MPE) is a common clinical problem of concern for most of the pneumologists and thoracic surgeons. A general consensus regarding the use of talc poudrage in treatment of MPE exists, but only few studies analyzed in detail talc insufflation related pulmonary morbidity. In particular, ARDS talc-related is caused by physical and chemical effects of the small talc particles (50% particle size <15 μm) and its occurrence is independent from the underlying disease, the quantity of talc used or the technique of talc instillation. In our series we observed 3 cases only (0.75%) of talc-related lung injury. This data strongly confirm the low rate of talc-related lung injury after talc poudrage in treatment of MPE regardless the amount of talc insufflated

Farnesyltransferase inhibitors and human malignant pleural mesothelioma: a first-step comparative translational study.

It is known that the potential clinical use of farnesyltransferase inhibitors (FTI) could be expanded to include cancers harboring activated receptor tyrosine kinases. Approximately 70% of malignant pleural mesotheliomas (MPM) overexpress epidermal growth factor receptors (EGFR) and a subset express both EGFR and transforming growth factor A (TGF-A), suggesting an autocrine role for EGFR in MPM. We checked on MPM cells (10 human cell lines, 11 primary cultures obtained by human biopsies, and 7 short-term normal mesothelial cell cultures) concerning the following: (a) the relative overexpression of EGFR (Western blotting, flow cytometry, immunohistochemistry), (b) the relative expression of EGFR ligands (EGF, amphiregulin, TGF-A, ELISA), (c) the relative increase of the activated form of Ras (Ras-bound GTP) after EGF stimulation (Ras activation assay), (d) the efficacy of five different FTIs (HDJ2 prenylation, cell cytotoxicity, and apoptosis using ApopTag and gel ladder). EGFR was overexpressed in MPM cells compared with normal pleural mesothelial cells in equivalent levels as in non\u2013small cell lung cancer cells A549. MPM cells constitutively expressed EGFR ligands; however, Ras activation was attenuated at high EGF concentrations (100 ng/mL). Growth of MPM cells was substantially not affected by treatment with different FTIs (SCH66336, BMS- 214662, R115777, RPR-115135, and Manumycin). Among these, BMS-214662 was the only one moderately active. BMS-214662 triggered apoptosis in a small fraction of cells (not higher than 30%) that was paralleled by a slight decrease in the levels of TGF-A secreted by treated MPM cells. Our data highlighted the concept that the same signaling pathway can be regulated in different ways and these regulations can differ between different cells of different origin

Survival analysis in single N2 station lung adenocarcinoma: The prognostic role of involved lymph nodes and adjuvant therapy

Background: Prognostic factors in patients with single mediastinal station (sN2) involvement continues to be a debated issue. Methods: Data on 213 adenocarcinoma patients with sN2 involvement and who had undergone complete anatomical lung resection and lymphadenectomy, were retrospectively reviewed. Clinical and pathological characteristics together with adjuvant therapy (AD) and node (N) status classifications (number of resected nodes (#RN), number of metastatic nodes (#MN), and node ratio (#MN/#RN = NR) were analyzed. Results: Univariable analysis confirmed that age (0.009), #MN (0.009), NR (0.003), #N1 involved stations (p = 0.003), and skip metastases (p = 0.005) were related to overall survival (OS). Multivariable analysis confirmed, as independent prognostic factors, age &lt;66 years and NR with a three-year OS (3YOS) of 78.7% in NR &lt; 10% vs. 46.6% in NR &gt; 10%. In skip metastases, NR (HR 2.734, 95% CI 1.417–5.277, p = 0.003) and pT stage (HR2.136, 95% CI 1.001–4.557, p = 0.050) were confirmed as independent prognostic factors. AD did not influence the OS of patients with singular positive lymph nodes (p = 0.41), while in patients with multiple lymph nodes and AD, a significantly better 3YOS was demonstrated, i.e., 49.1% vs. 30% (p = 0.004). In patients with N2 + N1 involvement, age (p = 0.002) and AD (p = 0.022) were favorable prognostic factors. Conclusions: Adenocarcinoma patients with single N2 station involvement had a favorable outcome in the case of skip metastases and low NR. Adjuvant therapy improves survival with multiple nodal involvement, while its role in single node involvement should be clarified

Risk factors for pancreas and lung neuroendocrine neoplasms: a case-control study.

Neuroendocrine neoplasia (NEN) has been displaying an incremental trend along the last two decades. This phenomenon is poorly understood, and little information is available on risk factor for neuroendocrine neoplasia development. Aim of this work is to elucidate the role of potentially modifiable risk factors for pancreatic and pulmonary NEN. We conducted a case-control study on 184 patients with NEN (100 pancreas and 84 lung) and 248 controls. The structured questionnaire included 84 queries on socio-demographic, behavioral, dietary and clinical information. Increased risk was associated with history of cancer ("other tumor", lung OR = 7.18; 95% CI: 2.55-20.20 and pancreas OR = 5.88; 95% CI: 2.43-14.22; "family history of tumor", lung OR = 2.66; 95% CI: 1.53-4.64 and pancreas OR = 1.94; 95% CI: 1.19-3.17; "family history of lung tumor", lung OR = 2.56; 95% CI: 1.05-6.24 and pancreas OR = 2.60; 95% CI: 1.13-5.95). Type 2 diabetes mellitus associated with an increased risk of pancreatic NEN (OR = 3.01; 95% CI: 1.15-7.89). Besides site-specific risk factors, there is a significant link between neuroendocrine neoplasia and cancer in general, pointing to a shared cancer predisposition

The International Thymic Malignancy Interest Group Classification of Thymoma Recurrence: Survival Analysis and Perspectives

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

Uniportal-VATS vs. open McKeown esophagectomy: Surgical and long-term oncological outcomes

Background: Till now there are very few reports about surgical results of Uniportal-VATS esophagectomy and no one about long-term outcomes. This study is the first comparing surgical and oncological outcomes of Uniportal-VATS with open McKeown esophagectomy, with the largest reported series and longest oncological follow-up. Methods: The prospectively collected clinical, surgical and oncological data of 75 patients, undergone McKeown esophagectomy at our Thoracic Surgery Department, from January 2012 to August 2022, were retrospectively analyzed. Nineteen patients underwent esophagectomy by thoracotomy and reconstruction according to McKeown technique while 56 by Uniportal-VATS approach. Gastric tubulization was performed totally laparoscopic or through a mini-laparatomic access and cervical anastomosis was made according to Orringer's technique. Results: The mean operative thoracic time was similar in both accesses (102.34 ± 15.21 min in Uniportal-VATS vs. 115.56 ± 23.12 min in open, p: 0.646), with a comparable number of mediastinal nodes retrieved (Uniportal-VATS:13.40 ± 8.12 vs. open:15.00 ± 6.86, p: 0.275). No case needed conversion from VATS to open. The learning curve in Uniportal-VATS was completed after 34 cases, while the Mastery was reached after 40. Both approaches were comparable in terms of minor post-operative complications (like pneumonia, lung atelectasis, anemization, atrial fibrillation, anastomotic-leak, left vocal cord palsy, chylothorax), while the number of re-operation for major complications (bleeding or mediastinitis) was higher in open group (21.0% vs. 3.6%, p: 0.04). Both techniques were also effective in terms of surgical radicality and local recurrence but VATS approach allowed a significantly lower chest tube length (11.89 ± 9.55 vs. 25.82 ± 24.37 days, p: 0.003) and post-operative stay (15.63 ± 11.69 vs. 25.53 ± 23.33, p: 0.018). The 30-day mortality for complications related to surgery was higher in open group (p: 0.002). The 2-, 5- and 8-year survival of the whole series was 72%, 50% and 33%, respectively. Combined 2- and 5-year OS in Uniportal-VATS group was 76% and 47% vs. 62% and 62% in open group, respectively (Log-rank, p: 0.286; Breslow-Wilcoxon: p: 0.036). No difference in DFS was recorded between the two approaches (5 year-DFS in Uniportal-VATS: 86% vs. 72%, p: 0.298). At multivariate analysis, only pathological stage independently affected OS (p: 0.02), not the surgical approach (p: 0.276). Conclusions: Uniportal-VATS seems to be a safe, feasible and effective technique for performing McKeown esophagectomy, with equivalent surgical and long-term oncological results to standard thoracotomy, but with a faster and unharmed recovery, and a quite short learning curve

Early Alpine occupation backdates westward human migration in Late Glacial Europe

Before the end of the Last Glacial Maximum (LGM, ∼16.5 ka ago) set in motion major shifts in human culture and population structure, a consistent change in lithic technology, material culture, settlement pattern, and adaptive strategies is recorded in Southern Europe at ∼18–17 ka ago. In this time frame, the landscape of Northeastern Italy changed considerably, and the retreat of glaciers allowed hunter-gatherers to gradually recolonize the Alps. Change within this renewed cultural frame (i.e., during the Late Epigravettian phase) is currently associated with migrations favored by warmer climate linked to the Bølling-Allerød onset (14.7 ka ago), which replaced earlier genetic lineages with ancestry found in an individual who lived ∼14 ka ago at Riparo Villabruna, Italy, and shared among different contexts (Villabruna Cluster). Nevertheless, these dynamics and their chronology are still far from being disentangled due to fragmentary evidence for long-distance interactions across Europe. Here, we generate new genomic data from a human mandible uncovered at Riparo Tagliente (Veneto, Italy), which we directly dated to 16,980–16,510 cal BP (2σ). This individual, affected by focal osseous dysplasia, is genetically affine to the Villabruna Cluster. Our results therefore backdate by at least 3 ka the diffusion in Southern Europe of a genetic component linked to Balkan/Anatolian refugia, previously believed to have spread during the later Bølling/Allerød event. In light of the new genetic evidence, this population replacement chronologically coincides with the very emergence of major cultural transitions in Southern and Western Europe.The research was supported by the European Union through the European Research Council under the European Union’s Horizon 2020 Research and Innovation Programme (grant agreement no. 724046 – Success awarded to S.B., http://www.erc-success.eu; grant agreement no. 803147 Resolution awarded to S.T., https://site.unibo.it/resolution-erc/en) as well as through the European Regional Development Fund (project no. 2014–2020.4.01.16–0030 to C.L.S. and T.S.) and projects no. 2014-2020.4.01.16-0024 and MOBTT53 (L.P.), by the Estonian Research Council personal research grant (PRG243; C.L.S.), and by UniPd PRID 2019 (L.P.).Peer reviewe