Lefkowitch, Jay H.

Abstract Context. —Establishing adequate interobserver agreement is crucial not only for standardization of patient care but also to ensure validity of findings in multi-institutional trials. Objective. —To evaluate interobserver agreement in assessing chronic hepatitis C (HCV) and acute cellular rejection (ACR) among 17 hepatopathologists involved in the “Hepatitis C 3” trial. Design. —The trial is a randomized multicenter (17 institutions) study involving 312 patients undergoing transplantation for HCV. Patients are randomized to 3 treatment arms. For final data analysis, all biopsy specimens are reviewed by a central pathologist (G.J.N.). Recurrence of HCV is evaluated according to the Batts and Ludwig schema. The 1997 Banff schema is used to evaluate ACR. To assess interobserver agreement, hematoxylin-eosin–stained sections from 11 liver biopsy specimens (6 HCV and 5 ACR) were sent by the central pathologist to 16 local pathologists from 13 institutions. Statistical analysis was performed on raw ACR/HCV data as well as data grouped according to clinically significant primary endpoint cutoffs. Results. —Statistically significant agreement was found among all participating pathologists ( P < .001). On κ analysis, the degree of agreement was rated “moderate” for HCV grade and stage and ACR global grading (κ = 0.30, 0.33, and 0.37, respectively). Interobserver agreement was weaker for rejection activity index scoring of ACR (κ = 0.15). A stronger degree of agreement was found when scores were grouped based on endpoint cutoffs (κ = 0.76 “almost perfect” for HCV and 0.62 “substantial” for ACR). Conclusions. —An overall statistically significant interobserver agreement was found among 17 pathologists using the 1997 Banff schema and the Batts and Ludwig schema.

Context HepPar-1 and Arginase-1 are urea cycle enzymes used to distinguish hepatocellular carcinoma from other carcinomas. HepPar-1, but not Arginase-1, is known to be immunoreactive with normal human small intestine. Objectives To better define and compare the immunohistochemical staining patterns of HepPar-1 and Arginase-1 in adenocarcinomas arising in the small intestine, including the ampullary region. Design Staining for HepPar-1 and Arginase-1 was performed on 20 nonampullary small intestinal adenocarcinomas and 32 adenocarcinomas from the ampullary region. Ampullary adenocarcinomas were divided into intestinal morphology (15), pancreatobiliary morphology (14), and unclassifiable (3). Nonneoplastic small intestinal mucosa and colorectal adenocarcinomas were used as control groups. Results HepPar-1 stained 12 of 20 nonampullary small intestinal adenocarcinomas, with a median of 63% of cells staining in positive cases. It also stained 11 of 15 ampullary carcinomas with intestinal morphology, with a median of 75% of cells staining in positive cases. Two of 14 ampullary carcinomas with pancreatobiliary morphology were positive for HepPar-1. Arginase-1 showed positivity in 2 ampullary region carcinomas and diffuse positivity in 1 duodenal adenocarcinoma. Two of 22 colorectal carcinomas stained for HepPar-1 with none positive for Arginase-1. Conclusions HepPar-1, but not Arginase-1, usually shows positivity in small intestinal adenocarcinomas and ampullary adenocarcinomas with intestinal morphology, but only rarely shows positivity in ampullary adenocarcinomas with pancreatobiliary morphology. HepPar-1 positivity in metastatic adenocarcinoma with intestinal morphology is suggestive of an upper gastrointestinal primary site.