Interpathologist Diagnostic Agreement for Non-Small Cell Lung Carcinomas Using Current and Recent Classifications.

CONTEXT.­: Measurement of interpathologist diagnostic agreement (IPDA) should allow pathologists to improve current diagnostic criteria and disease classifications. OBJECTIVES.­: To determine how IPDA for pathologists' diagnoses of non-small cell lung carcinoma (NSCLC) is affected by the addition of a set of mucin and immunohistochemical (IHC) stains to hematoxylin-eosin (H&E) alone, by recent NSCLC reclassifications, by simplification of these classifications, and by pathologists' practice location, pulmonary pathology expertise, practice duration, and lung carcinoma case exposure. DESIGN.­: We used a Web-based survey to present core images of 54 NSCLC cases to 22 practicing pathologists for diagnosis, initially as H&E only, then as H&E plus mucin and 4 IHC stains. Each case was diagnosed according to published 2004, 2011, and 2015 NSCLC classifications. Cohen's kappa was calculated for the 231 pathologist pairs as a measure of IPDA. RESULTS.­: Twenty-two pathologists diagnosed 54 NSCLC cases by using 4 published classifications. IPDA is significantly higher for H&E/mucin/IHC diagnoses than for H&E-only diagnoses. IPDA for H&E/mucin/IHC diagnoses is highest with the 2015 classification. IPDA is estimated higher after collapse of stated diagnoses into subhead or dichotomized classes. IPDA for H&E/mucin/IHC diagnoses with the 2015 World Health Organization classification is similar for community and academic pathologists, and is higher when pathologists have pulmonary pathology expertise, have more than 6 years of practice experience, or diagnose more than 100 new lung carcinoma cases per year. CONCLUSIONS.­: Higher IPDA is associated with use of mucin and IHC stains, with the 2015 NSCLC classification, and with pathologists' pulmonary pathology expertise, practice duration, and frequency of lung carcinoma cases.

Concurrent temozolomide and radiation, a reasonable option for elderly patients with glioblastoma multiforme?

OBJECTIVES: There is no accepted standard of care for patients over age 70 with glioblastoma (GBM). We began this study to describe our results and toxicities in the over 70 population treated with concurrent temozolomide and radiation for GBM, and to describe our outcomes treating elderly patients with GBM regardless of therapy. METHODS: We reviewed the records of all patients aged 70 or older who were diagnosed with glioblastoma since 2002 at the University of North Carolina to determine age at diagnosis, performance status, neurologic status, recursive partitioning analysis class, treatment received, and toxicity. Median survival was calculated according to the Kaplan-Meier method and compared by the Log-rank test. RESULTS: Thirty-one patients were identified with a median age of 76 years and a median survival of 20.6 weeks. Thirteen patients received best supportive care, 4 patients were treated with radiation alone, and 14 with radiation and concurrent temozolomide. The median survival for each group was 8.4, 28.2, and 50.5 weeks, respectively. Grade 1/2 toxicity was seen in 20% of patients, whereas only 1 patient had grade 3 toxicity. Neurologic status (P = 0.0028), performance status (P = 0.0096), and recursive partitioning analysis class (P = 0.0033) retained their prognostic significance. CONCLUSIONS: Concomitant daily temozolomide and radiation followed by adjuvant temozolomide is a tolerable and reasonable treatment option and has a good performance status for elderly patients diagnosed with glioblastoma.

UGT1A1 promoter genotype is not strongly associated with severity of coronary artery disease.

Atherosclerosis is a leading cause of morbidity and mortality. Oxidative stress is thought to play a role in its pathogenesis. Bilirubin is an endogenous antioxidant that is mildly elevated in people with Gilbert syndrome. Homozygosity for a A(TA)7TAA variant of the UDP-glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1) promoter is necessary for expression of the Gilbert phenotype. We studied the relationship between coronary artery disease (CAD) and the Gilbert genotype. Decedents who underwent autopsy were categorized into none/mild, moderate, and severe CAD groups based on autopsy findings. Known CAD risk factors were evaluated for each decedent in the severe CAD group (n=35), and for an age, race, and sex-matched control group with none/mild CAD (n=45). Formalin-fixed paraffin-embedded (FFPE) tissue was tested for UGT1A1 promoter variants by polymerase chain reaction and capillary electrophoresis. To our knowledge, this is the first study to successfully apply UGT1A1 promoter genotyping to formalin-fixed paraffin-embedded tissue, which may facilitate more thorough examination of clinicopathologic correlations. The frequency of the Gilbert genotype was compared between the none/mild cohort and the severe cohort. UGT1A1 promoter genotype data were obtained for 76/80 cases. The overall frequency of the Gilbert genotype compared well with previously reported frequencies at 16%, with a frequency of 16% in the none/mild CAD group and 15% in the severe CAD group. These findings suggest that UGT1A1 promoter genotype is not a major factor contributing to risk of CAD.