Citations

Abstract To identify the genetic factors that influence overall survival in never smokers who have non–small cell lung carcinoma (NSCLC), we conducted a consistency meta-analysis study using genome-wide association approaches for overall survival in 327 never smoker patients with NSCLC from The University of Texas MD Anderson Cancer Center (Houston, TX) and 293 cases from the Mayo Clinic (Rochester, MN). We then conducted a two-pronged validation of the top 25 variants that included additional validation in 1,256 patients with NSCLC from Taiwan and assessment of expression quantitative trait loci (eQTL) and differential expression of genes surrounding the top loci in 70 tumors and matched normal tissues. A total of 94 loci were significant for overall survival in both MD Anderson and Mayo studies in the consistency meta-analysis phase, with the top 25 variants reaching a P value of 10−6. Two variants of these 25 were also significant in the Taiwanese population: rs6901416 [HR, 1.44; 95% confidence interval (CI), 1.01–2.06] and rs10766739 (HR, 1.23; 95%CI, 1.00–1.51). These loci resulted in a reduction of median survival time of at least eight and five months in three populations, respectively. An additional six variants (rs4237904, rs7976914, rs4970833, rs954785, rs485411, and rs10906104) were validated through eQTL analysis that identified significant correlations with expression levels of six genes (LEMD3, TMBIM, ATXN7L2, SHE, ITIH2, and NUDT5, respectively) in normal lung tissue. These genes were also significantly differentially expressed between the tumor and normal lung tissue. These findings identify several novel, candidate prognostic markers for NSCLC in never smokers, with eQTL analysis suggesting a potential biologic mechanism for a subset of these observed associations. Cancer Res; 73(13); 4028–38. ©2013 AACR.

Pulmonary fibrosis in surgical lung biopsies is said to have a ‘usual interstitial pneumonia- pattern ’ (UIP- pattern ) of disease when scarring of the parenchyma is present in a patchy, ‘temporally heterogeneous’ distribution. These biopsies are one of the more common non-neoplastic specimens surgical pathologists encounter and often pose a number of challenges. UIP is the expected histopathological pattern in patients with clinical idiopathic pulmonary fibrosis (IPF), but the UIP- pattern can be seen in other conditions on occasion. Most important among these are the rheumatic interstitial lung diseases (RILD) and chronic hypersensitivity pneumonitis (CHrHP). Because theses entities have different mechanisms of injury, approach to therapy, and expected clinical progression, it is imperative for the surgical pathologist to correctly classify them. Taken in isolation, the UIP- pattern seen in patients with IPF may appear to overlap with that of RILD and CHrHP, at least when using the broadest definition of this term (patchy fibrosis). However, important distinguishing features are nearly always present in our experience, and the addition of a multidisciplinary approach will often resolve the critical differences between these diseases. In this manuscript, we review the distinguishing clinical, radiologic and histopathological features of UIP of IPF, RILD and CHrHP, based, in part, on the existing literature, but also lessons learned from a busy lung biopsy consultation practice.

Background. Balancing donor safety and graft volume is difficult. We previously reported that intentional modulation of portal venous pressure (PVP) during living-donor liver transplantation (LDLT) is crucial to overcoming problems with small-for-size grafts; however, detailed studies of portal venous flow (PVF) and a reliable parameter are still required. Patients and Methods. The elimination rate ( k) of indocyanine green (ICG) was measured in 49 adult LDLT recipients. PVP was controlled during LDLT, with a target of <20 mm Hg. ICG reflects hepatocyte volume and effective PVF. The kICG value is divided by the graft weight to calculate PVF. Recipients were divided into 2 groups: those with severe and/or fatal complications within 1 month after LDLT and those without. Results. Survival rates and postoperative profiles were significantly different between the 2 groups. Univariate analysis showed significant differences in ABO blood group, final PVP, final kICG, and the final kICG/graft weight value; however, multivariate analysis showed that only the kICG/graft weight value was significant. The cutoff level for the final kICG/graft weight value for predicting successful LDLT was 3.1175 × 10 −4 /g. Conclusion. Accurate evaluation and monitoring of optimal PVF during LDLT should overcome the use of small-for-size grafts and improve donor safety and recipient outcomes.