Background A phase 3, multinational, randomized, noninferiority trial (REFLECT) compared the efficacy and safety of lenvatinib (LEN) and sorafenib (SOR) in patients with unresectable hepatocellular carcinoma (uHCC). LEN had an effect on overall survival (OS) compared to SOR, statistically confirmed by non-inferiority [OS: median = 13.6 months vs. 12.3 months; hazard ratio (HR) 0.92, 95% confidence interval (CI) 0.79-1.06], and demonstrated statistically significant improvements in progression-free survival (PFS) and the objective response rate (ORR) in the overall population. The results of a subset analysis that evaluated the efficacy and safety of LEN and SOR in the Japanese population are reported. Methods The intent-to-treat population enrolled in Japan was analyzed. Results Of 954 patients in the overall population, 168 Japanese patients were assigned to the LEN arm (N = 81) Electronic supplementary material The online version of this article (

BACKGROUND The differential diagnosis between reactive mesothelial cells (RMs), malignant mesotheliomas (MMs), and adenocarcinomas (ACs) is often difficult in cytologic specimens, and the utility of various immunohistochemical markers have been explored. Because recent immunohistologic studies have suggested that E‐cadherin (E‐cad) and calretinin (Cal) may be useful markers for epithelial and mesothelial differentiations, respectively, the authors investigated their utility in cytologic diagnosis. METHODS In this retrospective study, immunostaining was performed on smears retrieved from Papanicolaou‐stained slides of effusions using the labeled streptavidin‐biotin method. Sixteen cases of RM, 9 cases of MM, and 52 cases of AC from various sites, including 13 pulmonary primaries, were examined with primary antibodies against E‐cad and Cal. RESULTS The positive rates for E‐cad and Cal, respectively, were as follows: RM, 0/16 (0%) and 16/16 (100%); MM, 9/9 (100%) and 8/8 (100%); and AC, 45/52 (86.5%) and 0/51 (0%). The E‐cad expression by neoplastic cells was strongest in the intercellular junctions, and poorly differentiated neoplastic cells in the single cell form showed the weakest expression. CONCLUSIONS In contrast to the results of previous immunohistochemical studies, the current study indicates that MMs constantly express E‐cad, whereas RMs lack its expression in cytologic specimens, which would be useful in the differential diagnosis between the two. On the other hand, E‐cad expression is not reliable for distinguishing AC from MM. The Cal expression can be a very useful marker for the distinction between AC and the mesothelial lineage. The combined immunostaining for E‐cad and Cal has utility in differential diagnosis among RM, MM, and AC. Cancer (Cancer Cytopathol) 2000;90:55–60. © 2000 American Cancer Society.

SummaryAmatuximab is a chimeric monoclonal antibody that targets mesothelin, which is expressed in virtually all mesotheliomas and pancreatic adenocarcinomas. The objective of this study was to determine the dose-limiting toxicity and the maximum tolerated dose. Patients with mesothelioma, pancreatic adenocarcinoma or other mesothelin-positive solid tumors were eligible for this study. Amatuximab was administered weekly as an intravenous infusion in 4-week cycles at progressively increasing doses ranging from 50 to 200 mg/m2. Seventeen patients received amatuximab. Two dose-limiting toxicities were observed: one at 50 mg/m2 and one at 200 mg/m2; the maximum tolerated dose of this study was determined to be 200 mg/m2. Of the 17 patients, 13 patients (76.5 %) experienced treatment-related adverse events. The most common adverse events were grade 1 fatigue (29.4 %) and pyrexia (23.5 %). The maximum serum concentration and area under the concentration curve values increased in an almost dose-proportional manner. Three patients had stable disease. Amatuximab was generally well tolerated at doses up to 200 mg/m2. The pharmacokinetic profile of amatuximab in the Japanese population was similar to that seen in the United States population (Clinical Trials.gov Identifier: NCT01018784).