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Background & Aims: Diverging trends of cholangiocarcinoma (CCA) incidence in different countries warrant further subtype‐specific characterization. In this study, we aimed to determine current epidemiologic trends of CCA in Germany and evaluated impact of misclassification of perihilar CCA (pCCA) as intrahepatic CCA (iCCA). Methods: Subtype‐specific incidence was assessed based on data of approximately 40 million German citizens from 2003 to 2014, and mortality data of entire Germany were assessed from 1998 to 2015. Results: Reclassification of pCCA to extrahepatic CCA (eCCA) led to an enhancement of an increasing average annual percentage change (AAPC) for iCCA in men (3.8 to 4.8) and women (3.3 to 4.8). Likewise, a stable or slightly decreasing trend in extrahepatic CCA was strengthened in women (AAPC: −0.2 to −0.9) and men (1 to 0.5). pCCA accounted for 13% of biliary tract tumours (iCCA: 46%, distal CCA: 41%). In line with incidence trends, mortality of iCCA in Germany increased for women (AAPC 7.8) and men (6.5), while it was stable for eCCA (women: −0.6, men: 2.1). Conclusion: Incidence of iCCA in Germany is increasing while it is stable for eCCA. Misclassification of pCCA as iCCA is present, but clearly declining. See Editorial on Page 260 [ABSTRACT FROM AUTHOR]

With an overall prevalence of 10–20%, gallstone disease (cholelithiasis) represents one of the most frequent and economically relevant health problems of industrialized countries. We performed an association scan of >500,000 SNPs in 280 individuals with gallstones and 360 controls. A follow-up study of the 235 most significant SNPs in 1,105 affected individuals and 873 controls replicated the disease association of SNP A-1791411 in ABCG8 (allelic P value PCCA = 4.1 × 10−9), which was subsequently attributed to coding variant rs11887534 (D19H). Additional replication was achieved in 728 German (P = 2.8 × 10−7) and 167 Chilean subjects (P = 0.02). The overall odds ratio for D19H carriership was 2.2 (95% confidence interval: 1.8–2.6, P = 1.4 × 10−14) in the full German sample. Association was stronger in subjects with cholesterol gallstones (odds ratio = 3.3), suggesting that His19 might be associated with a more efficient transport of cholesterol into the bile. [ABSTRACT FROM AUTHOR]

Background: Biliary tract cancer (BTC) has a high mortality. Primary diagnosis is frequently delayed due to mostly unspecific symptoms, resulting in a high number of advanced cases at the time of diagnosis. Advanced BTCs are in principle chemotherapy sensitive as determined by improved disease control, survival and quality of life (QoL). However, median OS does not exceed 11.7 months with the current standard of care gemcitabine plus cisplatin. Thereby, novel drug formulations like nanoliposomal-irinotecan (nal-IRI) in combination with 5- fluorouracil (5-FU)/leucovorin may have the potential to improve therapeutic outcomes in this disease.Methods: NIFE is an interventional, prospective, randomized, controlled, open label, two-sided phase II study. Within the study, 2 × 46 patients with locally advanced, non-resectable or metastatic BTC are to be enrolled by two stage design of Simon. Data analysis will be done unconnected for both arms. Patients are allocated in two arms: Arm A (experimental intervention) nal-IRI mg/m2, 46 h infusion)/5-FU (2400 mg/m2, 46 h infusion)/leucovorin (400 mg/m2, 0.5 h infusion) d1 on 14 day-cycles; Arm B (standard of care) cisplatin (25 mg/m2, 1 h infusion)/gemcitabine (1000 mg/m2, 0.5 h infusion) d1 and d8 on 21 day-cycles. The randomization (1:1) is stratified for tumor site (intrahepatic vs. extrahepatic biliary tract), disease stage (advanced vs. metastatic), age (≤70 vs. > 70 years), sex (male vs. female) and WHO performance score (ECOG 0 vs. ECOG 1). Primary endpoint of the study is the progression free survival (PFS) rate at 4 months after randomization by an intention-to-treat analysis in each of the groups. Secondary endpoints are the overall PFS rate, the 3-year overall survival rate, the disease control rate after 2 months, safety and patient related outcome with quality of life. The initial assessment of tumor resectability for locally advanced BTCs is planned to be reviewed retrospectively by a central surgical board. Exploratory objectives aim at establishing novel biomarkers and molecular signatures to predict response. The study was initiated January 2018 in Germany.Discussion: The NIFE trial evaluates the potential of a nanoliposomal-irinotecan/5-FU/leucovorin combination in the first line therapy of advanced BTCs and additionally offers a unique chance for translational research.Trial Registration: Clinicaltrials.gov NCT03044587. Registration Date February 7th 2017. [ABSTRACT FROM AUTHOR]

The article reports that over the past week, toads have reportedly been spontaneously exploding around a small pond in an upscale Hamburg suburb. Observers report that the amphibians crawl out of the water, swell to several times normal size, and then burst, their guts shooting a meter into the air. Nor have any toxins been found in tests of the water or in other pond organisms. A Berlin veterinary surgeon has suggested that crows peck holes in toads to get at their livers, and the toads swell up in self-defense. Samples of exploded toad tissue are being sent to labs, and it may take weeks to clear up the mystery.

The article focuses on the 39th Annual meeting of the European Association for the study of the Liver from April 15-19, 2004 in Berlin, Germany. The last date for the receipt of abstracts is November 16, 2003 and the last date for early registration is February 10, 2004.