Summary Background Limited data exist on the burden and features of non‐cirrhotic hepatocellular carcinoma (HCC) in the United States. Aim To evaluate characteristics, aetiologies, trends and outcomes of non‐cirrhotic HCC from 2000 to 2014 at five large US centres Methods Patient, tumour and liver disease aetiology data were collected. The presence of underlying cirrhosis was assessed based on published criteria. Results Of 5144 eligible patients with HCC, 11.7% had no underlying cirrhosis. Non‐cirrhotic patients were older (64.1 vs 61.2 years), more frequently females (33.9% vs 20.8%) and less frequently black (8.3% vs 12.4%) (P < .001 for all). Among non‐cirrhotic patients, non‐alcoholic fatty liver disease (NAFLD) was the most common liver disease (26.3%), followed by hepatitis C virus (HCV) (12.1%) and hepatitis B virus (HBV) (10%) infections. As of 2014, there was increased percentage of cirrhotic HCC and a decline in non‐cirrhotic HCC mainly due to significant annual increases in cirrhotic HCC due to HCV (0.96% [P < .0001]) and NAFLD (0.66% [P = .003]). Patients with non‐cirrhotic HCC had larger tumours (8.9 vs 5.3 cm), were less frequently within Milan criteria (15% vs 39%), more frequently underwent resection (43.6% vs 8%) (P < .001 for all) and had better overall survival than cirrhotic HCC patients (median 1.8 vs 1.3 years, P = .004). Conclusions Nearly 12% of HCCs occurred in patients without underlying cirrhosis. NAFLD was the most common liver disease in these patients. During the study, the frequency of non‐cirrhotic HCC decreased, whereas that of cirrhotic HCC increased. Although non‐cirrhotic patients presented with more advanced HCC, their survival was better.

BACKGROUND/OBJECTIVES Population‐based incidence estimates of dementia and Alzheimer disease (AD) provide important information for public health policy and resource allocation. We conducted a meta‐analysis of published studies that reported age‐specific incidence rates of dementia and AD to determine whether dementia and AD incidence rates are changing over time. DESIGN PubMed and MEDLINE were searched for publications through June 30, 2017, using key words “dementia”, “Alzheimer”, and “incidence.” Inclusion criteria for the meta‐analysis are: (1) population‐based studies using personal interviews and direct examinations of the study subjects, (2) standardized clinical diagnosis criteria, (3) reporting age‐specific incidence rates, (4) published in English, and (5) sample size of 500 or greater and length of follow‐up of 2 years or greater. Mixed‐effects models were used to determine the association between birth year and incidence rates. MEASUREMENTS Age‐specific dementia/AD incidence rates and their standard errors reported in each study. RESULTS Thirty‐eight articles with 53 cohorts on dementia incidence and 31 articles with 35 cohorts on AD incidence met the inclusion criteria. There were significant associations between later birth years and decreased dementia incidence rates in all three age groups (65‐74, 75‐84, and 85 years and older). There were no significant associations between birth year and AD incident rates in any of the three age groups. In particular, AD incidence rates reported from Western countries stayed steady in all age groups, while studies in non‐Western countries showed significantly increased AD incidence rates for the 65 to 74 years age group (odds ratio = 2.78; P = .04), but a nonsignificant association for the 75 to 84 or 85 years and older groups. CONCLUSION Dementia incidence declined over the past four decades, but AD incidence did not decline. Further research, especially from non‐Western countries, is needed to elucidate the mechanism underlying the trends in dementia and AD incidence over time.

BackgroundMost patients with resectable locally advanced esophageal and gastroesophageal junction (GEJ) adenocarcinoma (AC) receive concurrent chemoradiation (CRT) followed by esophagectomy. The majority of patients do not achieve pathologic complete response (pCR) with neoadjuvant CRT, and the relapse rate is high among these patients.MethodsWe conducted a phase II study (ClinicalTrials.gov Identifier: NCT02639065) evaluating the efficacy and safety of PD-L1 inhibitor durvalumab in patients with locally advanced esophageal and GEJ AC who have undergone neoadjuvant CRT followed by R0 resection with evidence of persistent residual disease in the surgical specimen. Patients received durvalumab 1500 mg IV every 4 weeks for up to 1 year. The primary endpoint was 1-year relapse free survival (RFS). Secondary endpoint was safety and tolerability of durvalumab following trimodality therapy. Exploratory endpoints included correlation of RFS with PD-L1 expression, HER-2 expression, and tumor immune cell population.ResultsThirty-seven patients were enrolled. The majority (64.9%) had pathologically positive lymph nodes. The most common treatment related adverse events were fatigue (27%), diarrhea (18.9%), arthralgia (16.2%), nausea (16.2%), pruritus (16.2%), cough (10.8%), and increase in AST/ALT/bilirubin (10.8%). Three (8.1%) patients developed grade 3 immune mediated adverse events. One-year RFS was 73% (95% CI, 56–84%) with median RFS of 21 months (95% CI, 14–40.4 months). Patients with GEJ AC had a trend toward superior 1-year RFS compared to those with esophageal AC (83% vs. 63%, p = 0.1534). There was a numerical trend toward superior 1-year RFS among patients with PD-L1 positive disease compared to those with PD-L1 negative disease, using CPS of ≥10 (100% vs. 66.7%, p = 0.1551) and ≥1 (84.2% vs. 61.1%, p = 0.1510) cutoffs. A higher relative proportion of M2 macrophages and CD4 memory activated T cells was associated with improved RFS (HR = 0.16; 95% CI, 0.05–0.59; p = 0.0053; and HR = 0.37; 95% CI, 0.15–0.93, p = 0.0351, respectively).ConclusionsAdjuvant durvalumab in patients with residual disease in the surgical specimen following trimodality therapy for locally advanced esophageal and GEJ AC led to clinically meaningful improvement in 1-year RFS compared to historical control rate. Higher PD-L1 expression may have a correlation with the efficacy of durvalumab in this setting. Higher proportion of M2 macrophages and CD4 memory activated T cells was associated with superior RFS.

Purpose: Genetic ancestry influences evolutionary pathways of cancers. However, whether ancestry influences cancer-induced field defects is unknown. The goal of this study was to utilize ancestry-mapped true normal breast tissues as controls to identify cancer-induced field defects in normal tissue adjacent to breast tumors (NATs) in women of African American (AA) and European (EA) ancestry.Experimental Design: A tissue microarray comprising breast tissues of ancestry-mapped 100 age-matched healthy women from the Komen Tissue Bank (KTB) at Indiana University (Indianapolis, IN) and tumor-NAT pairs from 100 women (300 samples total) was analyzed for the levels of ZEB1, an oncogenic transcription factor that is central to cell fate, mature luminal cell-enriched estrogen receptor alpha (ERa), GATA3, FOXA1, and for immune cell composition.Results: ZEB1 þ cells, which were localized surrounding the ductal structures of the normal breast, were enriched in the KTB-normal of AA compared with KTB-normal of EA women. In contrast, in EA women, both NATs and tumors compared with KTB-normal contained higher levels of ZEB1 þ cells. FOXA1 levels were lower in NATs compared with KTB-normal in AA but not in EA women. We also noted variations in the levels of GATA3, CD8 þ T cells, PD1 þ immune cells, and PDL1 þ cell but not CD68 þ macrophages in NATs of AA and EA women. ERa levels did not change in any of our analyses, pointing to the specificity of ancestrydependent variations.Conclusions: Genetic ancestry-mapped tissues from healthy individuals are required for proper assessment and development of cancer-induced field defects as early cancer detection markers. This finding is significant in light of recent discoveries of influence of genetic ancestry on both normal biology and tumor evolution. Conception and design: H. Nakshatri, C. D'Souza-Schorey Development of methodology: H. Nakshatri, M.L. Cox, G.E. Sandusky Acquisition of data (provided animals, acquired and managed patients, provided facilities, etc.): H. Nakshatri, M.L. Cox, M. Jacobsen, A.M.V. Storniolo Analysis and interpretation of data (e.g., statistical analysis, biostatistics, computational analysis):

INTRODUCTION: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide, affecting men to women at a ratio of about 4:1. Risk factors, characteristics, and outcomes for HCC in women in the United States remain poorly understood; therefore, we aim to explore gender differences further. METHODS: Patients diagnosed with HCC between January 2000 and June 2014 at 5 large centers were identified. Clinical information, tumor characteristics, and survival data were extracted manually. The presence of underlying cirrhosis was assessed based on published criteria. RESULTS: Of 5,327 patients with HCC in our cohort, 1,203 (22.6%) were women. There were important differences in the underlying etiology of liver disease between the 2 genders (P < 0.0001): women had a significantly higher frequency of nonalcoholic fatty liver disease (23% vs 12%) and lower frequency of alcoholic liver disease (5% vs 15%). The proportion of noncirrhotic HCC was significantly higher among women (17% vs 10%, P < 0.0001). Women had less-advanced HCC at presentation by tumor, node, metastasis staging (P < 0.0001) and a higher proportion within Milan criteria (39% vs 35%, P = 0.002). Women had a greater overall survival (2.5 ± 2.9 years vs 2.2 ± 2.7 years, P = 0.0031). DISCUSSION: The frequency of underlying nonalcoholic fatty liver disease and noncirrhotic HCC were significantly higher in women than men in this large cohort. Women presented with less-advanced HCC and had a greater overall survival. Further investigation is warranted to explore potential mechanisms and implications for these gender differences, especially with noncirrhotic HCC (see Visual Abstract, Supplementary Digital Content 1, http://links.lww.com/AJG/B535).