Search

Background: The advantages of video-assisted thoracic surgery (VATS) are well-recognized in several studies. However, in the cases of advanced lung cancer after neoadjuvant chemotherapy (nCT), the role of VATS is still questionable, with concerns about safety, technical feasibility, and oncological completeness. The aim of this study was to assess the impact of nCT on patients who had undergone uniportal VATS (U-VATS) anatomic lung resections for lung cancer, by comparing the short-term outcomes of patients after nCT with case-matched counterparts (treated by surgery alone)., Methods: We performed a retrospective, comparative study enrolling 927 patients (nCT: 60; non-nCT:867) who underwent U-VATS anatomic lung resections from 2014 to 2020 in two centers. Data were collected in a shared database with standardized variables' definition. Propensity score matching using 15 baseline preoperative patients' characteristics was performed in order to minimize selection-confounding factors between the two groups, which then were directly compared in terms of perioperative outcomes., Results: After propensity score matching, two groups of 60 patients had been defined. The nCT-group had a higher conversion rate compared to the control group (13.3% vs. 0%, p = 0.003) without an increase in operation time or cardiopulmonary complications. In addition, no differences between the two groups were recorded in terms of prolonged air leaks, length of stay, and readmission., Conclusions: U-VATS after nCT is a feasible approach, showing a similar rate of cardiopulmonary complications and length of stay when compared with the control group. However, it remains a challenging surgery due to its great technical complexity as well as the clinical status of the patients.

Background: Completion lobectomy (CL) following a prior resection in the same lobe may be complicated by severe pleural or hilar adhesions. The role of uniportal video-assisted thoracoscopic surgery (U-VATS) has never been evaluated in this setting., Methods: Data were collected from two Italian centers. Between 2015 and 2022, 122 patients (60 men and 62 women, median age 67.7 ± 8.913) underwent U-VATS CL at least 4 weeks after previous lung surgery., Results: Twenty-eight (22.9%) patients were affected by chronic obstructive pulmonary disease (COPD) and twenty-five (20.4%) were active smokers. Among the cohort, the initial surgery was performed using U-VATS in 103 (84.4%) patients, triportal-VATS in 8 (6.6%), and thoracotomy in 11 (9.0%). Anatomical segmentectomy was the initial surgery in 46 (37.7%) patients, while hilar lymphadenectomy was performed in 16 (13.1%) cases. CL was performed on 110 (90.2%) patients, segmentectomy on 10 (8.2%), and completion pneumonectomy on 2 (1.6%). Upon reoperation, moderate pleural adhesions were observed in 38 (31.1%) patients, with 2 (1.6%) exhibiting strong adhesions. Moderate hilar adhesions were found in 18 (14.8%) patients and strong adhesions in 11 (9.0%). The median operative time was 203.93 ± 74.4 min. In four (3.3%) patients, PA taping was performed. One patient experienced intraoperative bleeding that did not require conversion to thoracotomy. Conversion to thoracotomy was necessary in three (2.5%) patients. The median postoperative drainage stay and postoperative hospital stay were 5.67 ± 4.44 and 5.52 ± 2.66 days, respectively. Postoperative complications occurred in 34 (27.9%) patients. Thirty-day mortality was null. Histology was the only factor found to negatively influence intraoperative outcomes ( p = 0.000). Factors identified as negatively impacting postoperative outcomes at univariate analyses were male sex ( p = 0.003), age > 60 years ( p = 0.003), COPD ( p = 0.014), previous thoracotomy ( p = 0.000), previous S2 segmentectomy ( p = 0.001), previous S8 segmentectomy ( p = 0.008), and interval between operations > 5 weeks ( p = 0.005). In multivariate analysis, only COPD confirmed its role as an independent risk factor for postoperative complications (HR: 5.12, 95% CI (1.07-24.50), p = 0.04)., Conclusions: U-VATS CL seems feasible and safe after wedge resection and anatomical segmentectomy.

Irisin is a hormone-like myokine produced in abundance by skeletal muscle (SkM) in response to exercise. This myokine, identical in humans and mice, is involved in many signaling pathways related to metabolic processes. Despite much evidence on the regulators of irisin and the relevance of sphingolipids for SkM cell biology, the contribution of these latter bioactive lipids to the modulation of the myokine in SkM is missing. In particular, we have examined the potential involvement in irisin formation/release of sphingosine-1-phosphate (S1P), an interesting bioactive molecule able to act as an intracellular lipid mediator as well as a ligand of specific G-protein-coupled receptors (S1PR). We demonstrate the existence of distinct intracellular pools of S1P able to affect the expression of the irisin precursor FNDC. In addition, we establish the crucial role of the S1P/S1PR axis in irisin formation/release as well as the autocrine/paracrine effects of irisin on myoblast proliferation and myogenic differentiation. Altogether, these findings provide the first evidence for a functional crosstalk between the S1P/S1PR axis and irisin signaling, which may open new windows for potential therapeutic treatment of SkM dysfunctions.

In the last decade, the emergence of effective systemic therapies (ESTs) in the form of both targeted and immuno-based therapies has revolutionized the treatment of patients with advanced stage III and stage IV melanoma. Even though lungs represent the most frequent site of melanoma metastases, only limited data are available on the role of surgery in isolated pulmonary metastases from malignant melanoma (PmMM) in the era of ESTs. The aim of this study is to describe the outcomes of patients who underwent metastasectomy of PmMM in the era of ESTs, in order to identify prognostic factors affecting survival and to provide a framework for more informed patient selection of treatmeant with lung surgery in the future. Clinical data of 183 patients who underwent metastasectomy of PmMM between June 2008 and June 2021 were collected among four Italian Thoracic Centers. The main clinical, surgical and oncological variables reviewed were: sex, comorbidities, previous oncological history, melanoma histotypes and primary site, date of primary cancer surgical treatment, melanoma growth phase, Breslow thickness, mutation pattern disease, stage at diagnosis, metastatic sites, DFI (Disease Free Interval), characteristics of lung metastases (number, side, dimension, type of resection), adjuvant therapy after lung metastasectomy, site of recurrence, disease-free survival (DFS) and cancer-specific survival (CSS; defined as the time interval between the first melanoma resection or lung metastasectomy and death from cancer). All patients underwent surgical resection of the primary melanoma before lung metastasectomy. Twenty-six (14.2%) patients already had a synchronous lung metastasis at the time of primary melanoma diagnosis. A wedge resection was performed in 95.6% of cases to radically remove the pulmonary localizations, while an anatomical resection was necessary in the remaining cases. The incidence of major post-operative complications was null, while only 21 patients (11.5%) developed minor complications (mainly air leakage followed by atrial fibrillation). The mean in-hospital stay was 4.46 ± 2.8 days. Thirty- and sixty-day mortality were null. After lung surgery, 89.6% of the population underwent adjuvant treatments (47.0% immunotherapy, 42.6% targeted therapy). During a mean FUP of 107.2 ± 82.3 months, 69 (37.7%) patients died from melanoma disease, 11 (6.0%) from other causes. Seventy-three patients (39.9%) developed a recurrence of disease. Twenty-four (13.1%) patients developed extrapulmonary metastases after pulmonary metastasectomy. The CSS from melanoma resection was: 85% at 5 years, 71% at 10 years, 54% at 15 years, 42% at 20 years and 2% at 25 years. The 5- and 10-year CSS from lung metastasectomy were 71% and 26%, respectively. Prognostic factors negatively affecting CSS from lung metastasectomy at multivariable analysis were: melanoma vertical growth ( p = 0.018), previous metastatic sites other than lung ( p < 0.001) and DFI < 24 months ( p = 0.007). Our results support the evidence that surgical indication confirms its important role in stage IV melanoma with resectable pulmonary metastases, and selected patients can still benefit from pulmonary metastasectomy in terms of overall cancer specific survival. Furthermore, the novel systemic therapies may contribute to prolonged survival after systemic recurrence following pulmonary metastasectomy. Patients with long DFI, radial growth melanoma phase and no site of metastatization other than lung seem to be the best candidate cases for lung metastasectomy; however, to drive stronger conclusions, further studies evaluating the role of metastasectomy in patients with iPmMM are needed.

Background: The aim of this study was to evaluate the Masaoka-Koga and the tumor node metastases (TNM) staging system in thymic epithelial tumors (TET) considering possible improvements., Methods: We reviewed the data of 379 patients who underwent surgical resection for TET from 1 January 1985 to 1 January 2018, collecting and classifying the pathological report according to the Masaoka-Koga and the TMN system. The number of involved organs was also considered as a possible prognostic factor and integrated in the two staging systems to verify its impact., Results: Considering the Masaoka-Koga system, 5- and 10-year overall survival (5-10YOS) was 96.4% and 88.9% in stage I, 95% and 89.5% in stage II and 85.4% and 72.8% in stage III ( p = 0.01), with overlapping in stage I and stage II curves. Considering the TNM system, 5-10YOS was 95.5% and 88.8% in T1, 84.8% and 70.7% in T2 and 88% and 76.3% in T3 ( p = 0.02), with overlapping T2-T3 curves. Including the number of involved structures, in Masaoka-Koga stage III, patients with singular involved organs had a 100% and 76.6% vs. 87.7% 5-10YOS, which was 76.6% in patients with multiple organ infiltration. Considering the TNM, T3 patients with singular involved structures presented a 5-10YOS of 100% vs. 62.5% and 37.5% in patients with multiple organ involvement ( p = 0.07)., Conclusion: The two staging systems present limitations due to overlapping curves in early Masaoka-Koga stages and in advanced T stages for TNM. The addition of the number of involved organs seems to be a promising factor for the prognosis stratification in these patients.

Apart from cytokines and chemokines, sphingolipid mediators, particularly sphingosine-1-phosphate (S1P) and ceramide 1-phosphate (C1P), contribute to cancer and inflammation. Cancer, as well as other inflammatory conditions, are associated with skeletal muscle (SkM) atrophy, which is characterized by the unbalance between protein synthesis and degradation. Although the signaling pathways involved in SkM mass wasting are multiple, the regulatory role of simple sphingolipids is limited. Here, we report the impairment of ceramide kinase (CerK), the enzyme responsible for the phosphorylation of ceramide to C1P, associated with the accomplishment of atrophic phenotype in various experimental models of SkM atrophy: in vivo animal model bearing the C26 adenocarcinoma or Lewis lung carcinoma tumors, in human and murine SkM cells treated with the conditioned medium obtained from cancer cells or with the glucocorticoid dexamethasone. Notably, we demonstrate in all the three experimental approaches a drastic decrease of CerK expression. Gene silencing of CerK promotes the up-regulation of atrogin-1/MAFbx expression, which was also observed after cell treatment with C8-ceramide, a biologically active ceramide analogue. Conversely, C1P treatment significantly reduced the corticosteroid's effects. Altogether, these findings provide evidence that CerK, acting as a molecular modulator, may be a new possible target for SkM mass regulation associated with cancer or corticosteroids.

In this paper we aimed to address the role of pulmonary metastasectomy (PM) in patients affected by Lung Metastases (LM) from Renal Cell Carcinoma (RCC) and to analyse prognostic factors affecting overall survival (OS), disease-free interval (DFI) between primary RCC and first LM, and disease-free survival (DFS) after PM and before lung recurrence. Medical records of 210 patients who underwent PM from RCC in 4 Italian Thoracic Centres, from January 2000 to September 2019, were collected and analysed. All patients underwent RCC resection before lung surgery. The main RCC histology was clear cells (188, 89.5%). The 5- and 10-year OS from the first lung operation were 60% and 34%, respectively. LM synchronous with RCC ( p = 0.01) and (Karnofsky Performance Status Scale) KPSS < 80% ( p < 0.001) negatively influenced OS. Five- and 10-year DFI were 54% and 28%, respectively. The main factors negatively influencing DFI were: male gender ( p = 0.039), KPSS < 80% ( p = 0.009) and lactate dehydrogenase > 1.5 times 140 U/L ( p = 0.001). Five- and 10-year disease-free survival were 54% and 28%, respectively; multiple LM ( p = 0.036), KPSS < 80% ( p = 0.001) and histology of RCC other than clear cells negatively influenced disease-free survival. Conclusions: patients with KPSS > 80%, single metachronous LM with a long DFI from RCC diagnosis, and clear cell histology, benefit from pulmonary metastasectomy.

The recent coronavirus disease (COVID-19) is still spreading worldwide. The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the virus responsible for COVID-19, binds to its receptor angiotensin-converting enzyme 2 (ACE2), and replicates within the cells of the nasal cavity, then spreads along the airway tracts, causing mild clinical manifestations, and, in a majority of patients, a persisting loss of smell. In some individuals, SARS-CoV-2 reaches and infects several organs, including the lung, leading to severe pulmonary disease. SARS-CoV-2 induces neurological symptoms, likely contributing to morbidity and mortality through unknown mechanisms. Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid with pleiotropic properties and functions in many tissues, including the nervous system. S1P regulates neurogenesis and inflammation and it is implicated in multiple sclerosis (MS). Notably, Fingolimod (FTY720), a modulator of S1P receptors, has been approved for the treatment of MS and is being tested for COVID-19. Here, we discuss the putative role of S1P on viral infection and in the modulation of inflammation and survival in the stem cell niche of the olfactory epithelium. This could help to design therapeutic strategies based on S1P-mediated signaling to limit or overcome the host-virus interaction, virus propagation and the pathogenesis and complications involving the nervous system.

The bioactive sphingolipid metabolite, sphingosine 1-phosphate (S1P), and the signaling pathways triggered by its binding to specific G protein-coupled receptors play a critical regulatory role in many pathophysiological processes, including skeletal muscle and nervous system degeneration. The signaling transduced by S1P binding appears to be much more complex than previously thought, with important implications for clinical applications and for personalized medicine. In particular, the understanding of S1P/S1P receptor signaling functions in specific compartmentalized locations of the cell is worthy of being better investigated, because in various circumstances it might be crucial for the development or/and the progression of neuromuscular diseases, such as Charcot-Marie-Tooth disease, myasthenia gravis, and Duchenne muscular dystrophy.

Tissue damage, irrespective from the underlying etiology, destroys tissue structure and, eventually, function. In attempt to achieve a morpho-functional recover of the damaged tissue, reparative/regenerative processes start in those tissues endowed with regenerative potential, mainly mediated by activated resident stem cells. These cells reside in a specialized niche that includes different components, cells and surrounding extracellular matrix (ECM), which, reciprocally interacting with stem cells, direct their cell behavior. Evidence suggests that ECM stiffness represents an instructive signal for the activation of stem cells sensing it by various mechanosensors, able to transduce mechanical cues into gene/protein expression responses. The actin cytoskeleton network dynamic acts as key mechanotransducer of ECM signal. The identification of signaling pathways influencing stem cell mechanobiology may offer therapeutic perspectives in the regenerative medicine field. Sphingosine 1-phosphate (S1P)/S1P receptor (S1PR) signaling, acting as modulator of ECM, ECM-cytoskeleton linking proteins and cytoskeleton dynamics appears a promising candidate. This review focuses on the current knowledge on the contribution of S1P/S1PR signaling in the control of mechanotransduction in stem/progenitor cells. The potential contribution of S1P/S1PR signaling in the mechanobiology of skeletal muscle stem cells will be argued based on the intriguing findings on S1P/S1PR action in this mechanically dynamic tissue.