The Role of Endoscopic Ultrasound in the Interventional Management of Mediastinal Collections: A Narrative Review

The numerous causes underlying mediastinal lesions require different diagnostic and therapeutic approaches, including conservative, minimally invasive, and surgical interventions. Solid lesions of a malignant nature, mostly located in the anterior mediastinum, are properly treated with surgical resection either with or without adjuvant schemes. In contrast, a surveillance program is usually recommended with solid benign tumors, depending on their size and related symptomatology. In the management of mediastinal collections, when a drainage intervention is required (suspicion of infection and symptomatology), a minimally invasive nonsurgical procedure or thoracic surgery is considered. The minimally invasive nonsurgical procedures that can be available are percutaneous radiology-guided imaging (abdominal ultrasound (US) or computed tomography (CT) scan), complete single-aspiration guided by endoscopic ultrasound (EUS) or endobronchial ultrasound (EBUS), and transmural drainage guided by EUS. Surgical debridement is feasible to treat collections, but as this entails considerable risk of postoperative complications, it is chosen only when other minimally invasive therapies are not possible. The published literature related to the interventional endoscopic approach to mediastinal lesions is scarce. Nevertheless, reports in this field reveal that interventional EUS may have a role in both the diagnosis of and therapeutic approach to mediastinal lesions, mainly in the management of mediastinal collections

Uniportal robotic-assisted thoracoscopic surgery: resection of the first rib

A 39-year-old female patient presented with venous and neurogenic thoracic outlet syndrome, manifesting in positional pain and deep vein thrombosis (DVT) in the right upper extremity, accompanied by vascular redistribution. Her medical history was significant for surgical intervention for palmar hyperhidrosis (via a thoracoscopic approach) 15 years ago and second DVT in the right upper extremity in 2010, for which she received only limited anticoagulant treatment. She re-presented with symptoms suggestive of another DVT in the same region, meriting further investigation and management

The natural-based antitumor compound T21 decreases survivin levels through potent STAT3 inhibition in lung cancer models

Lung cancer is the leading cause of cancer-related deaths worldwide; hence novel treatments for this malignancy are eagerly needed. Since natural-based compounds represent a rich source of novel chemical entities in drug discovery, we have focused our attention on tambjamines, natural compounds isolated from marine invertebrates that have shown diverse pharmacological activities. Based on these structures, we have recently identified the novel indole-based tambjamine analog 21 (T21) as a promising antitumor agent, which modulates the expression of apoptotic proteins such as survivin. This antiapoptotic protein plays an important role in carcinogenesis and chemoresistance. In this work, we have elucidated the molecular mechanism by which the anticancer compound T21 exerts survivin inhibition and have validated this protein as a therapeutic target in di erent lung cancer models. T21 was able to reduce survivin protein levels in vitro by repressing its gene expression through the blockade of Janus kinase/Signal Transducer and Activator of Transcription-3 (JAK/STAT3)/survivin signaling pathway. Interestingly, this occurred even when the pathway was overstimulated with its ligand interleukin 6 (IL-6), which is frequently overexpressed in lung cancer patients who show poor clinical outcomes. Altogether, these results show T21 as a potent anticancer compound that e ectively decreases survivin levels through STAT3 inhibition in lung cancer, appearing as a promising therapeutic drug for cancer treatment

Prognostic value of the preoperative lymphocyte-to-monocyte ratio for survival after lung cancer surgery

Background: Tthe aim of this study was to assess the effect of the lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio on overall survival and disease-free survival in patients with lung cancer treated with radical surgery. Methods: we performed a retrospective review of patients with lung cancer who prospectively underwent radical resection between 2004 and 2012. Blood samples were taken as part of the preoperative workup. The inflammatory markers studied were absolute values of lymphocytes, monocytes, neutrophils and platelets, with subsequent calculation of ratios. Median follow-up was 52 months. Results: two hundred and sixty-eight patients underwent surgery, of whom 218 (81.3%) were men. Mean age was 62.9 ± 8.7 years. A lymphocyte-to-monocyte ratio ≥ 2.5 was independently associated with longer disease-free survival (hazard ratio [HR] 0.476 (0.307-0.738), p = 0.001) and longer overall survival (HR, 0.546; 95% CI: 0.352-0.846; p = 0.007), in models adjusted for age, sex, stage, and type of resection. No other systemic inflammatory marker showed a significant association. Conclusion: preoperative LMR is an independent prognostic factor of overall survival and recurrence-free survival in patients with surgically-resected early stage lung cancer

A Comparison of Total Thoracoscopic and Robotic Surgery for Lung Cancer Lymphadenectomy

Background: Robotic-assisted thoracic surgery (RATS) is used increasingly frequently in major lung resection for early stage non-small-cell lung cancer (NSCLC) but has not yet been fully evaluated. The aim of this study was to compare the surgical outcomes of lymph node dissection (LND) performed via RATS with those from totally thoracoscopic (TT) four-port videothoracoscopy. Methods: Clinical and pathological data were collected retrospectively from patients with clinical stage N0 NSCLC who underwent pulmonary resection in the form of lobectomy or segmental resection between June 2010 and November 2022. The assessment criteria were number of mediastinal lymph nodes and number of mediastinal stations dissected via the RATS approach compared with the four-port TT approach. Results: A total of 246 pulmonary resections with LND for clinical stages I-II NSCLC were performed: 85 via TT and 161 via RATS. The clinical characteristics of the patients were similar in both groups. The number of mediastinal nodes dissected and mediastinal stations dissected was significantly higher in the RATS group (TT: mean ± SD, 10.72 ± 3.7; RATS, 14.74 ± 6.3 [p < 0.001]), except in the inferior mediastinal stations. There was no difference in terms of postoperative complications. Conclusions: In patients with early stage NSCLC undergoing major lung resection, the quality of hilomediastinal LND performed using RATS was superior to that performed using TT

Airway Complications after Lung Transplantation—A Contemporary Series of 400 Bronchial Anastomoses from a Single Center

(1) Objective: To determine whether recent advances in lung transplantation (LT) have reduced the incidence and changed the risk factors for airway complications (AC). (2) Methods: Retrospective analysis of patients receiving a lung transplant between January 2007 and January 2019. An AC was defined as a bronchoscopic abnormality in the airway, either requiring or not requiring an endoscopic or surgical intervention. Both univariable and multivariable analyses were performed to identify risk factors for AC. (3) Results: 285 lung transplants (170 single and 115 bilateral lung transplants) were analysed, comprising 400 anastomoses at risk. A total of 50 anastomoses resulted in AC (12%). There were 14 anastomotic and 11 non-anastomotic stenoses, 4 dehiscences, and 3 malacias. Independent predictors for AC were: gender male (OR: 4.18; p = 0.002), cardiac comorbidities (OR: 2.74; p = 0.009), prolonged postoperative mechanical ventilation (OR: 2.5; p = 0.02), PaO2/FiO2 < 300 mmHg at 24 h post-LT (OR: 2.48; p = 0.01), graft infection (OR: 2.16; p = 0.05), and post-LT isolation of Aspergillus spp. (OR: 2.63; p = 0.03). (4) Conclusions: In spite of advances in lung transplantation practice, the risk factors, incidence, and lethality of AC after LT remains unchanged. Graft dysfunction, an infected environment, and the need of prolonged mechanical ventilation remain an Achilles heel for AC

Preoperative omega-6/omega-3 fatty acid ratio could predict postoperative outcomes in patients with surgically resected non-small-cell lung cancer

Introduction: The aim of this study was to determine whether preoperative nutritional status and inflammatory status, specifically polyunsaturated acids and the omega 6/3 ratio, would affect postoperative outcomes and complications in patients with lung cancer undergoing lung resection. Methods: This prospective observational study included 68 patients with early-stage non-small-cell lung cancer who were candidates for radical surgery. A complete nutritional assessment was performed. The primary study variable was postoperative complications and mortality in the first 30 days. Descriptive, bivariate, and logistic regression analyses were carried out. Results: A total of 50 men (73.53%) and 18 women (26.47%) underwent surgery, with a median age of 64.2 (±9.74) years. The mean omega 6/3 ratio was 17.39 (±9.45). A complication occurred in 39.7% of the study sample (n = 27), the most common being persistent air leak in 23.53% (n = 16). After performing the bivariate analysis, the only variable that remained significant was the omega 6/3 ratio; we observed that it had a prognostic value for persistent air leak (p = 0.001) independent of age, sex, comorbidity, preoperative respiratory function, and approach or type of surgery. The remaining nutritional and inflammatory markers did not have a statistically significant association (p > 0.05) with postoperative complications. However, this significance was not maintained in the multivariate analysis by a small margin (p = 0.052; 95% CI: 0.77-1.41). Conclusions: Omega 6/3 ratio may be a prognostic factor for air leak, independent of the patient's clinical and pathological characteristics

The influence of preoperative nutritutional and systemic inflamatory status on perioperative outcomes following Da Vinci robot-assisted thoracic lung cancer surgery

Background: Nutrition is an important factor in the outcome of any disease process. We evaluated the relationship of nutritional status and inflammatory status of non-small cell lung cancer (NSCLC) patients undergoing robotic-assisted thoracic surgery (RATS) with postoperative complications. Methods: This prospective cohort study included 107 NSCLC patients undergoing surgical treatment, between 2019 and 2021. Nutritional status and inflammatory status were assessed before pulmonary resection using anthropometric assessment, blood tests, and body mass index (BMI). Results: The BMI was 27.5 ± 4.4. Based on BMI, 29% (n = 31) were classified as normal weight, 43% (n = 46) as overweight, and 28% (n = 30) as obese. The mean neutrophil/lymphocyte ratio (NLR) was 2.16 ± 0.85, the platelet/lymphocyte ratio (PLR) was 121.59 ± 44.21, and the lymphocyte/monocyte ratio (LMR) was 3.52 ± 1.17. There was no increase in the number of intraoperative complications or bleeding (p = 0.696), postoperative complications (p = 0.569), mean hospital stay (p = 0.258) or duration of chest drain (p = 0.369). Higher inflammatory status, with an NLR > 1.84, was associated with more overall postoperative complications (p = 0.028), only in univariate analysis, but this significance was not maintained on multivariate analysis. Conclusions: BMI was not a predictor of increased postoperative risk in this cohort; therefore, weight should not deter surgeons from using RATS for pulmonary resection

Evaluation of the inflammatory responses to sol-gel coatings with distinct biocompatibility levels

[EN] The immune system plays a crucial role in determining the implantation outcome, and macrophages are in the frontline of the inflammatory processes. Further, cellular oxidative stress resulting from the material recognition can influence how cell responses develop. Considering this, the aim of this study was to study oxidative stress and macrophages phenotypes in response to sol-gel materials with distinct in vivo outcomes. Four materials were selected (70M30T and 35M35G30T, with high biocompatibility, and 50M50G and 50V50G, with low biocompatibility). Gene expression, immunocytochemistry and cytokine secretion profiles for M1 and M2 markers were determined. Moreover, oxidative stress markers were studied. Immunocytochemistry and ELISA showed that 50M50G and 50V50G lead to a higher differentiation to M1 phenotype, while 70M30T and 35M35G30T promoted M2 differentiation. In oxidative stress, no differences were found. These results show that the balance between M1 and M2, more than individual quantification of each phenotype, determines a biomaterial outcome.Generalitat Valenciana, Grant/Award Number: GRISOLIAP/2018/091; Ministerio de Economia y Competitividad, Grant/Award Numbers: MAT2017-86043-R, RTC2017-6147-1; Universitat Jaume I, Grant/Award Number: POSDOC/2019/28Cerqueira, A.; Araújo-Gomes, N.; Zhang, Y.; Van Den Beucken, JJJP.; Martínez-Ramos, C.; Ozturan, S.; Izquierdo, R.... (2021). Evaluation of the inflammatory responses to sol-gel coatings with distinct biocompatibility levels. Journal of Biomedical Materials Research Part A. 109(9):1539-1548. https://doi.org/10.1002/jbm.a.37149S15391548109

Integrative transcriptome analysis of malignant pleural mesothelioma reveals a clinically relevant immune-based classification

Background: Malignant pleural mesothelioma (MPM) is a rare and aggressive neoplasia affecting the lung mesothelium. Immune checkpoint inhibitors (ICI) in MPM have not been extremely successful, likely due to poor identification of suitable candidate patients for the therapy. We aimed to identify cellular immune fractions associated with clinical outcome and classify patients with MPM based on their immune contexture. For each defined group, we sought for molecular specificities that could help further define our MPM classification at the genomic and transcriptomic level, as well as identify differential therapeutic strategies based on transcriptional signatures predictive of drug response. Methods: The abundance of 20 immune cell fractions in 516 MPM samples from 7 gene expression datasets was inferred using gene set variation analysis. Identification of clinically relevant fractions was performed with Cox proportional-hazards models adjusted for age, stage, sex, and tumor histology. Immune-based groups were defined based on the identified fractions. Results: T-helper 2 (TH2) and cytotoxic T (TC) cells were found to be consistently associated with overall survival. Three immune clusters (IG) were subsequently defined based on TH2 and TC immune infiltration levels: IG1 (54.5%) was characterized by high TH2 and low TC levels, IG2 (37%) had either low or high levels of both fractions, and IG3 (8.5%) was defined by low TH2 and high TC levels. IG1 and IG3 groups were associated with worse and better overall survival, respectively. While no differential genomic alterations were identified among immune groups, at the transcriptional level, IG1 samples showed upregulation of proliferation signatures, while IG3 samples presented upregulation of immune and inflammation-related pathways. Finally, the integration of gene expression with functional signatures of drug response showed that IG3 patients might be more likely to respond to ICI. Conclusions: This study identifies a novel immune-based signature with potential clinical relevance based on TH2 and TC levels, unveiling a fraction of patients with MPM with better prognosis and who might benefit from immune-based therapies. Molecular specificities of the different groups might be used to tailor specific potential therapies in the future