Validation of interobserver agreement in lung cancer assessment: hematoxylin-eosin diagnostic reproducibility for non-small cell lung cancer: the 2004 World Health Organization classification and therapeutically relevant subsets.

CONTEXT: Precise subtype diagnosis of non-small cell lung carcinoma is increasingly relevant, based on the availability of subtype-specific therapies, such as bevacizumab and pemetrexed, and based on the subtype-specific prevalence of activating epidermal growth factor receptor mutations. OBJECTIVES: To establish a baseline measure of interobserver reproducibility for non-small cell lung carcinoma diagnoses with hematoxylin-eosin for the current 2004 World Health Organization classification, to estimate interobserver reproducibility for the therapeutically relevant squamous/nonsquamous subsets, and to examine characteristics that improve interobserver reproducibility. DESIGN: Primary, resected lung cancer specimens were converted to digital (virtual) slides. Based on a single hematoxylin-eosin virtual slide, pathologists were asked to assign a diagnosis using the 2004 World Health Organization classification. Kappa statistics were calculated for each pathologist-pair for each slide and were summarized by classification scheme, pulmonary pathology expertise, diagnostic confidence, and neoplastic grade. RESULTS: The 12 pulmonary pathology experts and the 12 community pathologists each independently diagnosed 48 to 96 single hematoxylin-eosin digital slides derived from 96 cases of non-small cell lung carcinoma resection. Overall agreement improved with simplification from the comprehensive 44 World Health Organization diagnoses (κ  =  0.25) to their 10 major header subtypes (κ  =  0.48) and improved again with simplification into the therapeutically relevant squamous/nonsquamous dichotomy (κ  =  0.55). Multivariate analysis showed that higher diagnostic agreement was associated with better differentiation, better slide quality, higher diagnostic confidence, similar years of pathology experience, and pulmonary pathology expertise. CONCLUSIONS: These data define the baseline diagnostic agreement for hematoxylin-eosin diagnosis of non-small cell lung carcinoma, allowing future studies to test for improved diagnostic agreement with reflex ancillary tests.

Neoadjuvant clinical trial with sorafenib for patients with stage II or higher renal cell carcinoma.

PURPOSE: The multitargeted tyrosine kinase inhibitor sorafenib is used for the treatment of advanced-stage renal cell carcinoma. However, the safety and efficacy of this agent have yet to be evaluated in the preoperative period, where there may be potential advantages including tumor downstaging. This prospective trial evaluates the safety and feasibility of sorafenib in the preoperative setting. PATIENTS AND METHODS: Thirty patients with clinical stage II or higher renal masses, selected based on their candidacy for nephrectomy, underwent preoperative treatment with sorafenib. Toxicities, surgical complications, and tumor responses were monitored. RESULTS: Of the thirty patients enrolled, 17 patients had localized disease and 13 had metastatic disease. After a course of sorafenib therapy (median duration, 33 days), a decrease in primary tumor size (median, 9.6%) and radiographic evidence of loss of intratumoral enhancement, quantified using a methodology similar to Choi criteria (median, 13%), was also observed. According to Response Evaluation Criteria in Solid Tumors, of the 28 patients evaluable for response, two patients had a partial response and 26 had stable disease, with no patients progressing on therapy. Toxicities from sorafenib were similar to that expected with this class of medication. All patients were able to proceed with nephrectomy and no surgical complications related to sorafenib administration were observed. CONCLUSION: The administration of preoperative sorafenib therapy can impact the size and density of the primary tumor and appears safe and feasible. Further studies are required to determine if preoperative systemic therapy improves outcomes in patients undergoing nephrectomy for renal cell carcinoma.

Evolution of Pap testing at a community hospital: a ten year experience.

Over a 10-year period the Pap program at our community hospital laboratory progressed from the use of 100% conventional smears to predominantly ThinPrep (TP) and then to nearly 100% SurePath (SP). During this period the annual Pap volume grew from less than 20,000 to nearly 50,000. This retrospective review focuses on improvements in high-grade squamous intraepithelial lesion (HSIL) detection rates and specimen adequacy rates during the 10-year period. The laboratory database was used to identify 310,080 Pap test records between 1995 and 2004 inclusive. Pap type differences in HSIL detection rates and specimen adequacy rates were examined using the Cochran-Mantel-Haenszel test, with year as the stratification variable. The Breslow-Day test was used to evaluate the consistency of differences across the years. The overall results are summarized below in tabular format. Results of Combined 10-Year Data for Total Number of Cases, HSIL Rate, and Unsatisfactory Specimen Rate by Pap Method are given: [table: see text]. HSIL detection rates were significantly higher for liquid-based Pap tests compared with conventional smears (P < 0.0001). In addition, SP was associated with higher HSIL detection rates than TP with an estimated common odds ratio (OR) of 1.37 (95% confidence interval (CI), 1.10 - 1.71; P = 0.005), and higher specimen adequacy compared with TP or conventional Pap methods (P < 0.0001).