Veno-venous extra-corporeal membrane oxygenation in complex tracheobronchial resection.

Background: Elective extra-corporeal membrane oxygenation (ECMO) is rarely used in thoracic surgery, apart from lung transplantation. The purpose of this study was to summarize our institutional experience with the intraoperative use of veno-venous (VV) ECMO in selected cases of main airway surgery. Methods: We retrospectively analyzed the data of 10 patients who underwent main airway surgery with the support of VV-ECMO between June 2013 and August 2022. Results: Surgical procedures included: three carinal resection and reconstruction with complete preservation of the lung parenchyma, one right upper double-sleeve lobectomy and hemi-carinal resection, and one sleeve resection of the left main bronchus after previous right lower bilobectomy, for thoracic malignancies; four tracheal/carinal repair for extensive traumatic laceration; one extended tracheal resection due to post-tracheostomy stenosis in a patient who had previously undergone a left pneumonectomy. The median intraoperative VV-ECMO use was 162.5 minutes. In three cases with complex resection and reconstruction of the carina and in one case of extended post-tracheostomy stenosis and previous pneumonectomy, high-flow VV-ECMO allowed interruption of ventilation for almost 3 hours. In four patients, VV-ECMO was prolonged in the postoperative period to ensure early extubation. There were no perioperative deaths, no complications related to the use of ECMO and no intraoperative change in the planned type of ECMO. Significant complications occurred only in one patient who developed a small anastomotic dehiscence that led to stenosis and required placement of a Montgomery tube. At the median follow-up of 30 months, all 10 patients were still alive. Conclusions: The use of intraoperative VV-ECMO allows safe and precise performance of main airway surgery with minimal postoperative morbidity in patients requiring complex resections and reconstructions and in cases that cannot be managed with conventional ventilation techniques.

Complex Sleeve Lobectomy Has Lower Postoperative Major Complications Than Pneumonectomy in Patients with Centrally Located Non-Small-Cell Lung Cancer.

BACKGROUND: Standard sleeve lobectomies are recommended over pneumonectomy (PN), but the efficacy and oncological proficiency of complex sleeve lobectomies (CSLs) have not been completely investigated. The aim of this study was to report our experience in CSL in patients affected by a centrally located non-small-cell lung cancer (NSCLC), comparing all the variables and outcomes with PN. METHODS: From 2014 to 2022, we collected the data of patients who underwent PN and CSL for NSCLC, excluding neuroendocrine tumors, salvage surgery or carinal resection. Regression analysis was used to assess the association between procedures and complications; the Kaplan-Meier method and Cox regression analysis were used to evaluate survival and risk factors of reduced survival. RESULTS: We analyzed n = 38 extended sleeve lobectomies and n= 6 double-sleeve lobectomies (CSL group) and n= 60 PNs. We had a trend toward higher postoperative mortality in the PN group (5% vs. 0%, p = 0.13). Major complications and bronchial fistula developed in 21.7% and 6.8% (p = 0.038) and in 6.7% and 4.5% (p = 0.64), respectively. The right side was identified as risk factor for major complications, whereas age > 70 and PN had a trend of association in multivariable analysis. The median OS was similar between the two groups (p = 0.76) and cancer recurrence was the only significant risk factors of reduced OS. Excluding functionally compromised patients, the OS of CSL was better than that of PN (67% vs. 42%, p = 0.25). CONCLUSIONS: Considering that major complications are often associated with mortality after surgery for centrally located NSCLC, CSLs could be considered an alternative to PN while also ensuring comparable survival.

Development of predictive models for assessing the progression and invasiveness of satellite lesions in patients with multiple pulmonary ground glass nodules.

Background: Currently, the appropriate treatment of satellite lesions is still controversial. With this study, we aimed to construct a set of nomograms to determine the characteristics of satellite lesions in patients with multiple pulmonary ground glass nodules (MPGGNs) and propose a reference for the management of satellite lesions. Methods: We retrospectively analyzed patients with MPGGNs who had undergone multiple rounds of surgical resection of primary and satellite lesions, including pathologic examinations after surgical resection. Results: A total of 125 lesions from 105 patients were included in the analysis; 85 lesions were advanced and 40 lesions were not advanced. Among them, 55 invasive pulmonary adenocarcinomas (IPA) and 70 noninvasive pulmonary adenocarcinomas were identified. After the final regression analysis, the patients' age, satellite lesion location, consolidation tumor ratio (CTR), lesion border clarity, and lesion diameter were used to predict satellite lesion progression. Patients' gender, satellite lesion location, lesion diameter, and computed tomography (CT) attenuation values were used to predict the invasiveness of the satellite lesion. The constructed nomograms showed strong discrimination with concordance indices (C indices) of 0.816 and 0.823, respectively. Conclusions: We developed a set of nomograms that can predict the risk of advanced or invasive satellite lesions in patients with MPGGNs. The area under the receiver operating characteristic (ROC) curve (AUC), the C-index, and the calibration curve suggest that the nomogram may be useful in the clinical setting. This model has the potential to help clinicians make treatment recommendations for the remaining lesions while treating the primary lesion in patients with MPGGNs.

Presentation and treatment of two massive intrapericardial lipoma. Case report.

INTRODUCTION AND IMPORTANCE: Primary pericardial tumors are very rare with an overall incidence of 0.001-0.007 % and account for approximately 10 % of heart neoplasms. We present two clinical cases of massive mature intrapericardial lipomas (maximum size 270 × 230 mm) that were successfully treated in our department. CASE PRESENTATION: The first case is that of a 67-year-old male patient who underwent diagnostic investigations after the onset of dyspnea, which confirmed an intrapericardial mass of 270 × 230 mm in size that extended into the left lung field and was treated surgically by a clamshell incision. The second case is that of a 48-year-old patient who was completely asymptomatic and occasionally confirmed to have a 170 × 110 mm intrapericardial mass around the heart, which was surgically removed via sternotomy, also resulting in a mature lipoma. CLINICAL DISCUSSION: In asymptomatic patients with small lesions, close monitoring is generally indicated. In asymptomatic patients with large lesions the decision should be made after multidisciplinary (MDT) evaluation. In symptomatic patients, surgical treatment is indicated. Lipomas are usually mature lesions with a capsule connected to the origin structure by one or more pedicles. Once reached the cardiac level and opened the pericardium, attention must be paid in resecting these pedicles given the area of origin and the possibility that they may be associated with vital structures. CONCLUSION: Both cases were characterized by slow recovery of normal cardiac function in the postoperative course. The average length of patient stay was 12 days, and one case was noted for readmission because a slight increase in pericardial effusion was detected at the scheduled ultrasound check after discharge. After further expert evaluation and steriodine therapy, the patient was discharged to a healthy home after 5 days. This report aims to describe the decision-making process, successful surgical treatment and outcomes of two rare massive intrapericardial tumors.

Lung Segmentectomy in NSCLC Surgery.

Current guidelines recommend surgery for early-stage non-small cell lung cancer (NSCLC). The standard treatment for patients with cT1N0 NSCLC has been lobectomy with lymph-node dissection, with sublobar resection used only in patients with inadequate cardio-respiratory reserve, with poor performance status, or who are elderly. In 1995, the Lung Cancer Study Group published the results of a randomized, prospective trial demonstrating the superiority of lobectomy compared with sublobar resection. From then on, wedge resection and segmentectomy were reserved exclusively for patients with poor functional reserve who could not tolerate lobectomy. Therefore, the exact role of segmentectomy has been controversial over the past 20 years. Recently, the randomized controlled trial JCOG0802/WJOG4607L demonstrated that segmentectomy was superior to lobectomy in patients with stage IA NSCLC (<2 cm and CTR < 0.5) in terms of both overall-survival and post-operative lung function. Based on these results, segmentectomy should be considered the standard surgical procedure for this patient group. In 2023, the randomized phase III CALGB 140503 (Alliance) trial demonstrated the efficacy and non-inferiority of sublobar resection, including wedge resection, for clinical stage IA NSCLC with tumor diameter of < 2 cm. This article is a narrative review of the current role of segmentectomy in lung cancer treatment and summarizes the most relevant studies in this context.

Does thoracoscopic basal pyramid segmentectomy really offer functional advantages in comparison with thoracoscopic lower lobectomy?

OBJECTIVES: The functional impact of thoracoscopic basal segmentectomy in comparison with lower lobectomy has not been investigated in-depth and the aim of this study was to clarify this topic. METHODS: We retrospectively analysed a cohort of patients who underwent surgery between 2015 and 2019 for non-small-cell lung cancer, peripherally located lung nodules, far enough from both the apical segment and the lobar hilum to allow an oncologically safe thoracoscopic lower lobectomy or basal segmentectomy. Pulmonary function tests (PFTs) including spirometry and plethysmography were performed 1 month after surgery and forced expiratory volume in 1 s, forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO) were collected; the difference, the loss and the recovery rate of pulmonary function were calculated and compared with the Wilcoxon-Mann-Whitney test. RESULTS: During the study period, n = 45 and n = 16 patients for video-assisted thoracoscopic surgery (VATS) lower lobectomy and for VATS basal segmentectomy, respectively, completed the study protocol: the 2 groups were homogeneous as to preoperative variables and PFT values. Postoperative outcomes were similar and PFTs revealed significant differences between postoperative forced expiratory volume in 1 s %, FVC%, ΔFVC and ΔFVC%. The loss percentage of FVC%, DLCO% and the recovery rate was better for FVC and DLCO in the VATS basal segmentectomy group. CONCLUSIONS: Thoracoscopic basal segmentectomy seems to be associated with a more preserved lung function, maintaining more FVC and DLCO levels than lower lobectomy, and could be performed in selected cases ensuring also adequate oncological margins.

A new preoperative localization of pulmonary nodules guided by mixed reality: a pilot study of an animal model.

Background: With the popularity of high-resolution computed tomography (HRCT), more and more pulmonary nodules are being discovered. Video-assisted thoracoscopic surgery (VATS) has become the first choice for surgical treatment of pulmonary nodules. The use of accurate preoperative localization is crucial for successful resection in VATS. At present, there are many kinds of preoperative localization methods, but there are certain disadvantages. This study aimed to evaluate the feasibility and safety of mixed reality (MR)-guided pulmonary nodules localization, which is a new method that can benefit patients to a greater extent. Methods: By constructing an animal model of pulmonary nodules localization, 28 cases of pulmonary nodules were located by MR-guided localization. We recorded the localization accuracy, localization time, insertion attempts, and incidence of complications related to localization under MR-guidance. Results: All 28 nodules were successfully located: the deviation of MR-guided localization was 5.71±2.59 mm, localization time was 8.07±1.44 min, and insertion attempts was 1. A pneumothorax and localizer dislodgement occurred in 1 case, respectively. Conclusions: Since preoperative localization is critical for VATS resection of pulmonary nodules, we investigated a new localization method. As indicated by our study, MR-guided localization of pulmonary nodules is feasible and safe, which is worthy of further research and promotion. We have also registered corresponding clinical trials to further investigate and help to improve our understanding of this technique.

Post-operative and early oncological results of simple and complex full thoracoscopic segmentectomies for non-small-cell lung cancer.

BACKGROUND: The role of video-assisted thoracoscopic segmentectomy in the treatment of clinical IA non-small-cell lung cancer is not well established. The aim of our retrospective analysis was to evaluate the oncological results of complex and simple video-assisted thoracoscopic segmentectomy. METHODS: From 2015 to June 2020, data of n = 163 consecutive patients undergoing video-assisted thoracoscopic segmentectomy for solitary pulmonary nodule were analysed. The Kaplan-Meier method, log-rank test and Cox regression were used to estimate, compare survivals and identify risk factors of worse oncological outcomes. RESULTS: In this period, n = 123 patients underwent video-assisted thoracoscopic segmentectomy for non-small-cell lung cancer: we performed n = 65 simple and n = 58 complex video-assisted thoracoscopic segmentectomy; n = 99 (80.5%) had a solid appearance on computed tomography scan and n = 78 (63.4%) a moderate-to-high [18F]-2-fluoro-2-deoxy-D-glucose (FDG)-positron emission tomographic computed tomography scan avidity. Mortality was 0%, and complications occurred in n = 14 (21.5%) and 9 (15.5%) patients. The median follow-up was 24 (range: 6-60) months and the 5-year overall survival was 96% without difference between video-assisted thoracoscopic segmentectomies (p = 0.16). Local recurrence developed in n = 2 (3.1%) and n = 3 (5.2%) patients; regional in n = 2 (3.1%) and 1 (1.8%) and distant in 8 (12.3%) and 2 (3.4%), without difference between video-assisted thoracoscopic segmentectomies (p = 0.51). The overall 5-year disease-free survival rate was 78%. Pathological upstaging was observed in n = 13 patients (nodal in n = 6, tumour in n = 7) and it was the only significant factor for worse disease-free survival at the multivariable analysis (hazard ratio: 2.43, 95% CI: 1.04-8.68, p = 0.049), value confirmed also in the group of intended video-assisted thoracoscopic segmentectomy (p = 0.047). CONCLUSIONS: Pathological upstaging after simple or complex video-assisted thoracoscopic segmentectomy is a risk factor for recurrence and then video-assisted thoracoscopic segmentectomy should be considered an appropriate therapeutic option for selected stage IA non-small-cell lung cancer patients.

Markers of Bronchiolitis Obliterans Syndrome after Lung Transplant: Between Old Knowledge and Future Perspective.

Bronchiolitis obliterans syndrome (BOS) is the most common form of CLAD and is characterized by airflow limitation and an obstructive spirometric pattern without high-resolution computed tomography (HRCT) evidence of parenchymal opacities. Computed tomography and microCT analysis show abundant small airway obstruction, starting from the fifth generation of airway branching and affecting up to 40-70% of airways. The pathogenesis of BOS remains unclear. It is a multifactorial syndrome that leads to pathological tissue changes and clinical manifestations. Because BOS is associated with the worst long-term survival in LTx patients, many studies are focused on the early identification of BOS. Markers may be useful for diagnosis and for understanding the molecular and immunological mechanisms involved in the onset of BOS. Diagnostic and predictive markers of BOS have also been investigated in various biological materials, such as blood, BAL, lung tissue and extracellular vesicles. The aim of this review was to evaluate the scientific literature on markers of BOS after lung transplant. We performed a systematic review to find all available data on potential prognostic and diagnostic markers of BOS.

Chest-Wall Tumors and Surgical Techniques: State-of-the-Art and Our Institutional Experience.

The chest wall can be involved in both primary and secondary tumors, and even today, their management and treatment continue to be a challenge for surgeons. Primary chest-wall tumors are relatively rare and include a large group of neoplasms that can arise from not only bone or cartilage of the chest wall but also from associated subcutaneous tissue from muscle and blood vessels. Secondary tumors refer to a direct invasion of the chest wall by neoplasms located elsewhere in the body, mainly metastases from breast cancer and lung cancer. En-bloc surgical excision of the lesion should ensure adequate negative margins to avoid local recurrence, and a full thickness surgical resection is often required, and it can result in important chest-wall defects such as skeletal instability or impaired breathing dynamics. The reconstruction of large defects of the chest wall can be complex and often requires the use of prosthetic and biologic mesh materials. This article aims to review the literature on these tumor entities, focusing on the main surgical techniques and the most recent advances in chest-wall resection and reconstruction. We also report on the institutional experience our center.

Long-term outcomes of robot-assisted radical thymectomy for large thymomas: A propensity matched analysis.

BACKGROUND: The aim of this study was to evaluate the long-term results of robot-assisted (RATS) thymectomy in the treatment of large thymomas, defined as larger than 5 cm. METHODS: We retrospectively reviewed 106 thymectomies from 2010 to 2020, creating two groups based on the surgical approach (open or RATS) and size. Kaplan-Meier and Cox-regression were used to estimate and identify risk factors of oncological outcomes. To perform a well-balanced analysis, a propensity score matched (PSM) analysis was conducted for large thymomas. RESULTS: From 2015, we performed 54 RATS thymectomies: 53.7% (n = 29) for small and 46.3% (n = 25) for large thymomas. Conversions were similar and all patients had a complete resection. The overall (82% vs. 92%, p = 0.57) and disease-free survival were comparable between RATS and open (92.5% vs. 93%, p = 0.67), outcomes confirmed after PSM for large thymomas. CONCLUSIONS: RATS thymectomy could be considered a valid option in selected patients with large thymomas.

Extracorporeal membrane oxygenation support in carinal resection for recurrent chondrosarcoma after previous distal tracheal resection.

Carinal re-resection for tumour recurrence is rarely performed due to increased difficulty in airway reconstruction. We reported a successful case of carinal resection and reconstruction for recurrent chondrosarcoma after previous distal tracheal resection. Due to the technical complexity of the reconstruction and the poor respiratory reserve of the patient, the veno-venous extracorporeal membrane oxygenation support was used.

Clinical courses and outcomes of five patients with primary lung cancer surgically treated while affected by Severe acute respiratory syndrome coronavirus 2.

OBJECTIVES: There is currently a lack of clinical data on the novel beta-coronavirus infection [caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)] and concomitant primary lung cancer. Our goal was to report our experiences with 5 patients treated for lung cancer while infected with SARS-CoV-2. METHODS: We retrospectively evaluated 5 adult patients infected with SARS-CoV-2 who were admitted to our thoracic surgery unit between 29 January 2020 and 4 March 2020 for surgical treatment of a primary lung cancer. Clinical data and outcomes are reported. RESULTS: All patients were men with a mean age of 74.0 years (range 67-80). Four of the 5 patients (80%) reported chronic comorbidities. Surgery comprised minimally invasive lobectomy (2 patients) and segmentectomy (1 patient), lobectomy with en bloc chest wall resection (1 patient) and pneumonectomy (1 patient). Mean chest drain duration was 12.4 days (range 8-22); mean hospital stay was 33.8 days (range 21-60). SARS-CoV-2-related symptoms were fever (3 patients), persistent cough (3 patients), diarrhoea (2 patients) and syncope (2 patients); 1 patient reported no symptoms. Morbidity related to surgery was 60%; 30-day mortality was 40%. Two patients (1 with a right pneumonectomy, 74 years old; 1 with a lobectomy with chest wall resection and reconstruction, 70 years old), developed SARS-CoV-2-related lung failure leading to death 60 and 32 days after surgery, respectively. CONCLUSIONS: Lung cancer surgery may represent a high-risk factor for developing a severe case of coronavirus disease 2019, particularly in patients with advanced stages of lung cancer. Additional strategies are needed to reduce the risk of morbidity and mortality from SARS-CoV-2 infection during treatment for lung cancer.

Short and mid-term outcomes of multimodal treatment for locally-advanced non-small cell lung cancer in elderly patients.

OBJECTIVE: Multimodality treatments are effective for locally advanced non-small cell lung cancer (LA-NSCLC) showing benefits in overall (OS) and disease-free survival (DFS), but these options are frequently denied to elderly patients. METHODS: The objectives of this retrospective study were: to investigate mortality, morbidity and oncological outcomes of pulmonary resection after induction therapy (IT) for NSCLC in elderly patients. We divided the cohort into two: patients < 70 years (group A) and patients ≥70 years (group B). A multivariable logistic regression was built to identify factors associated with morbidity. RESULTS: 77 patients underwent pulmonary resection after IT, 27 were aged ≥70 years. Type of chemotherapy, surgical procedures, pathological stages were comparable between the two groups, while the preoperative use of chemo-radiation therapy regimen was more frequent in group A (p = 0.027). In-hospital mortality was similar, while the percentage of patients with complications (38% vs 48.1%, p = 0.47) and the complication rate (50% vs 77%, p = 0.01) were higher in group B, but the severity of complications was comparable. The multivariable analysis did not identify any risk factors associated with morbidity. OS at 3 years and DFS at 2 years were not different (61% vs 48.5%, p = 0.64; 61.7% vs 44%, p = 0.393). CONCLUSIONS: Lung resection for LA-NSCLC after IT can be performed safely in selected elderly patients with favourable postoperative and mid-term oncological results.

Antidepressant-like effect of artemin in mice: a mechanism for acetyl-L-carnitine activity on depression.

RATIONALE: Depression may be associated with altered plasticity of the nervous system. The importance of neurotrophic factor levels is strongly suggested, and the neuronal-related family is extensively studied with respect to glial-derived one. OBJECTIVES: Aimed to contribute to the study of nervous plasticity modulation as therapeutical target in mood disorders, the role of the glial-derived factor artemin (ARTN) in depression and in the pharmacodynamics of the antidepressant and trophic compound acetyl-L: -carnitine (ALCAR) was evaluated. METHODS: Male mice were treated with 100 mg kg(-1) ALCAR daily for 7 days; 0.6 µg/mouse ARTN was acutely injected intracerebroventricularly. Gene knockdown of ARTN and GDNF family receptor alpha (GFRalpha3) was obtained by oligonucleotide antisense strategy. The forced swimming test was performed to evaluate antidepressant-like effects. RESULTS: Repeated ALCAR administration increased ARTN levels in spinal cord, hippocampus, and prefrontal cortex. No modulatory effect was detected on BDNF and glial cell line-derived neutrotrophic factor (GDNF). ARTN, 30 min after administration, showed a dose-dependent antidepressant-like effect. ALCAR needed a 7-day treatment to reach a comparable effect; nevertheless, both substances were able to induce a phosphorylation of the GDNF family receptor Ret. A decrease of the free ARTN level by a specific ARTN antibody impaired the antidepressant-like effect of acute ARTN and repeated ALCAR. Gene knockdown of ARTN or, alternatively, of its receptor GFRalpha3 fully prevented ALCAR effectiveness. CONCLUSIONS: A mechanism for the antidepressant property of ALCAR is proposed, and the novelty of the possible role of ARTN in depression is suggested.

Design, synthesis and nootropic activity of new analogues of sunifiram and sapunifiram, two potent cognition-enhancers.

A series of amides and sulfonamides, structurally related to DM235 (sunifiram) and MN19 (sapunifiram), derived by ring expansion or contraction, or by inversion of the exocyclic amide function, have been synthesized and tested for cognition-enhancing activity in the mouse passive-avoidance test. Some of the compounds display good antiamnesic and procognitive activity, with higher potency than piracetam, and with a potency similar to the parent compounds.