Cytokine Biomarkers as Indicators of Primary Graft Dysfunction, Acute Rejection, and Chronic Lung Allograft Dysfunction in Lung Transplant Recipients: A Review

Lung transplantation is well accepted form of treatment for end-stage lung disease in selected patients. The number of lung transplants performed worldwide has increased annually with chronic obstructive pulmonary disease being the leading cause. The morbidity and mortality in the early period are due to nonspecific primary graft dysfunction (PGD) and acute lung rejection (ALR). Chronic lung allograft dysfunction (CLAD) is the cause of long-term complications following lung transplantation and seen in almost half of the patient during the first 5 years. Activation of pro- and anti-inflammatory cytokines and chemokines has been described during various phases of lung transplantation recovery. We reviewed the literature for cytokine activity associated with PGD, ALR, and CLAD. This review aims to summarize the specific associations between bronchoalveolar lavage (BAL) and plasma cytokine levels and the association of PGD, ALR, and CLAD

Video-Assisted Thoracoscopy in the Management of Primary and Secondary Pneumothorax

The management of primary and secondary spontaneous pneumothorax can have many variations depending on the surgeons and their expertise of practice. The end goal is to stop the recurrence. The history of treatment, clinical indications for surgery, and preoperative and postoperative decision-making for intervention are summarized. Surgical intervention plays an important role in the management of recurrent pneumothorax and complex initial pneumothorax. Over the years the surgical techniques have evolved, and currently, video-assisted thoracoscopic techniques are frequently used in the management. In this concise report, we attempt to analyze the surgical techniques currently in use and their outcomes. Furthermore, we attempt to integrate future innovations in the management of this common disorder

Improved Survival Associated with Neoadjuvant Chemoradiation in Patients with Clinical Stage IIIA(N2) Non–Small-Cell Lung Cancer

IntroductionOptimal management of clinical stage IIIA-N2 non–small-cell lung cancer (NSCLC) is controversial. This study examines whether neoadjuvant chemoradiation plus surgery improves survival rates when compared with other recommended treatment strategies.MethodsAdult patients from the National Cancer Database, with clinical stage IIIA-N2 disease definitively treated between 1998 and 2004 at American College of Surgeons Commission on Cancer accredited facilities, were included in the study. Treatment was defined as neoadjuvant chemoradiation plus either lobectomy (NeoCRT+L) or pneumonectomy (NeoCRT+P), lobectomy plus adjuvant therapy (L+AT), pneumonectomy plus adjuvant therapy (P+AT), and concurrent chemoradiation (CRT). Median follow-up and overall survival (OS) were defined from date of diagnosis to last contact. Five-year OS was estimated using Kaplan–Meier methods. Cox proportional hazard regression was used to estimate hazard ratios and 95% confidence intervals (CIs), adjusting for sociodemographic, clinical, and facility characteristics.ResultsMedian follow-up was 11.8 months for 11,242 eligible patients. Five-year OS was 33.5%, 20.7%, 20.3%, 13.35%, and 10.9% for NeoCRT+L, NeoCRT+P, L+AT, P+AT, and CRT, respectively (p < 0.0001). On multivariable analysis, the estimated hazard ratio was 0.51 (CI: 0.45–0.58) for NeoCRT+L; 0.77 (0.63–0.95) for NeoCRT+P; 0.66 (0.59–0.75) for L+AT; 0.69 (0.54–0.88) for P+AT; and 1.0 (reference) for the CRT group. Comorbidity did not attenuate the relationship between treatment and survival.ConclusionThis large study demonstrates that patients with clinical stage IIIA-N2 NSCLC, who underwent neoadjuvant chemoradiation followed by lobectomy, were associated with an improved survival

EPHA2 mutations with oncogenic characteristics in squamous cell lung cancer and malignant pleural mesothelioma.

Squamous cell carcinoma (SCC) and malignant pleural mesothelioma (MPM) are thoracic malignancies with very poor prognosis and limited treatment options. It is an established fact that most of the solid tumors have overexpression of EPHA2 receptor tyrosine kinase. EPHA2 is known to exhibit opposing roles towards cancer progression. It functions in inhibiting cancer survival and migration via a ligand and tyrosine kinase dependent signaling (Y772). Whereas it is known to promote tumor progression and cell migration through a ligand-independent signaling (S897). We analyzed the expression profile and mutational status of the ephrin receptor A2 (EPHA2) in SCC and MPM cell lines and primary patient specimens. The EPHA2 receptor was found to be either overexpressed, mutated or amplified in SCC and MPM. In particular, the EPHA2 mutants A859D and T647M were interesting to explore, A859D Y772 dead mutant exhibited lower levels of phosphorylation at Y772 compared to T647M mutant. Molecular Dynamics simulations studies suggested that differential changes in conformation might form the structural basis for differences in the level of EPHA2 activation. Consequently, A859D mutant cells exhibited increased proliferation as well as cell migration compared to controls and T647M mutant. Kinomics analysis demonstrated that the STAT3 and PDGF pathways were upregulated whereas signaling through CBL was suppressed. Considered together, the present work has uncovered the oncogenic characteristics of EPHA2 mutations in SSC and MPM reinstating the dynamics of different roles of EPHA2 in cancer. This study also suggests that a combination of doxazosin and other EPHA2 inhibitors directed to inhibit the pertinent signaling components may be a novel therapeutic strategy for MPM and Non-small cell lung cancer patients who have either EPHA2 or CBL alterations

Epidemiology of lung cancer and the gender differences in risk

Background: Lung cancer has progressed from an exceedingly rare disease to the leading cause of all cancer-related deaths, a phenomenon largely attributed to the impact of tobacco smoking and resulting global epidemic. Methods: A thorough literature search was conducted to identify relevant factors in the epidemiology of lung cancer with a focus on recent studies and developments that had the most significant impact on the current understanding of lung cancer. Results: Most recent data suggests the global burden of lung cancer is continuing to rise with 2.2 million new cases in 2020 alone. Although no difference is noted among men, a higher rate of lung cancer deaths among women in the industrialized countries are observed compared to developing nations. Incidence and deaths are closely linked to cigarette smoking. Other risk factors include occupational hazards, increasing air pollution with pulmonary infectious diseases and inflammatory conditions, and genetic factors. Tobacco continues to cause approximately 90% of all lung cancer deaths with a markedly wide variety of incidence rates both geographically and between males and females. Lung cancer incidence has been falling in US and UK since 1990 largely due to comprehensive tobacco control programs. In contrast higher rates of cigarette smoking among emerging nations is a concern. The unprecedented, widespread adoption of electronic-cigarette use among adolescents may pose major obstacles in the prevention and treatment of lung cancer. Conclusions: While the vast majority of current lung cancer cases and deaths continue to be caused by tobacco consumption, shifts in population behaviors, geographical location, and potential new causes may alter this distribution. Further work is crucial in order to better understand the risk factors for lung cancer in the modern world so that a more holistic proactive approach, rather than a reactive approach, can be taken