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

Surgical treatment of pulmonary hypertension: Lung transplantation

Pulmonary hypertension (PH) is a serious and progressive disorder that results in right ventricular dysfunction that lead to subsequent right heart failure and death. When untreated the median survival for these patients is 2.8 years. Over the past decade advances in disease specific medical therapy considerably changed the natural history. This is reflected in a threefold decrease in the number of patients undergoing lung transplantation for PH which used to be main stay of treatment. Despite the successful development of medical therapy lung transplant still remains the gold standard for patients who fail medical therapy. Referral for lung transplant is recommended when patients have a less than 2-3 years of predicted survival or in NYHA class III or IV. Both single and bilateral lung transplants have been successfully performed for PH but outcome analyses and survival comparisons generally favor a bilateral lung transplant