Anchoring fins of fully covered self-expandable metal stents affect pull-out force and stent migration.

BACKGROUND AND AIMS: Stent migration and subsequent adverse events are frequently observed in the use of fully covered self-expandable metal stents (FCSEMSs) for distal biliary stenosis. In this study, we identified predictors for stent migration based on biomechanical stent characteristics and associated these findings with clinical outcomes. METHODS: The migration resistance of FCSEMSs was quantified by measuring the pull-out force. We analyzed a single-center retrospective cohort of 178 FCSEMSs for treatment success and adverse events occurring during 180 days of follow-up. RESULTS: Biomechanical measurements revealed a 4-fold higher migration resistance of FCSEMSs with anchoring fins (AF-FCSEMSs; Fmax = 14.2 ± .1 N) compared with FCSEMSs with flared ends (FE-FCSEMSs; Fmax = 3.8 ± 1.0 N; P < .0001). Clinically, AF-FCSEMSs showed lower rates of migration compared with FE-FCSEMSs (5% vs 34%, P < .0001). Unscheduled ERCP procedures because of stent dysfunction were less frequent in the AF group compared with the FE group (15% vs 29%, P = .046). Cholangitis because of stent dysfunction was observed in 5% of the AF group compared with 19% in the FE group (P = .02). Stent patency rates at 1, 3, and 6 months were higher in the AF group (96%, 90%, and 80%, respectively) compared with the FE group (90%, 74%, and 66%; log-rank test: P = .03). CONCLUSIONS: The pull-out force as a biomechanical stent property predicts the migration resistance of FCSEMSs in distal biliary stenosis and may thus be used to classify stents for this application. AF-FCSEMSs showed a significantly lower rate of migration and adverse events compared with FE-FCSEMSs.

Genetic variation in TERT modifies the risk of hepatocellular carcinoma in alcohol-related cirrhosis: results from a genome-wide case-control study.

OBJECTIVE: Hepatocellular carcinoma (HCC) often develops in patients with alcohol-related cirrhosis at an annual risk of up to 2.5%. Some host genetic risk factors have been identified but do not account for the majority of the variance in occurrence. This study aimed to identify novel susceptibility loci for the development of HCC in people with alcohol related cirrhosis. DESIGN: Patients with alcohol-related cirrhosis and HCC (cases: n=1214) and controls without HCC (n=1866), recruited from Germany, Austria, Switzerland, Italy and the UK, were included in a two-stage genome-wide association study using a case-control design. A validation cohort of 1520 people misusing alcohol but with no evidence of liver disease was included to control for possible association effects with alcohol misuse. Genotyping was performed using the InfiniumGlobal Screening Array (V.24v2, Illumina) and the OmniExpress Array (V.24v1-0a, Illumina). RESULTS: Associations with variants rs738409 in PNPLA3 and rs58542926 in TM6SF2 previously associated with an increased risk of HCC in patients with alcohol-related cirrhosis were confirmed at genome-wide significance. A novel locus rs2242652(A) in TERT (telomerase reverse transcriptase) was also associated with a decreased risk of HCC, in the combined meta-analysis, at genome-wide significance (p=6.41×10-9, OR=0.61 (95% CI 0.52 to 0.70). This protective association remained significant after correction for sex, age, body mass index and type 2 diabetes (p=7.94×10-5, OR=0.63 (95% CI 0.50 to 0.79). Carriage of rs2242652(A) in TERT was associated with an increased leucocyte telomere length (p=2.12×10-44). CONCLUSION: This study identifies rs2242652 in TERT as a novel protective factor for HCC in patients with alcohol-related cirrhosis.

The rs429358 Locus in Apolipoprotein E Is Associated With Hepatocellular Carcinoma in Patients With Cirrhosis.

The host genetic background for hepatocellular carcinoma (HCC) is incompletely understood. We aimed to determine if four germline genetic polymorphisms, rs429358 in apolipoprotein E (APOE), rs2642438 in mitochondrial amidoxime reducing component 1 (MARC1), rs2792751 in glycerol-3-phosphate acyltransferase (GPAM), and rs187429064 in transmembrane 6 superfamily member 2 (TM6SF2), previously associated with progressive alcohol-related and nonalcoholic fatty liver disease, are also associated with HCC. Four HCC case-control data sets were constructed, including two mixed etiology data sets (UK Biobank and FinnGen); one hepatitis C virus (HCV) cohort (STOP-HCV), and one alcohol-related HCC cohort (Dresden HCC). The frequency of each variant was compared between HCC cases and cirrhosis controls (i.e., patients with cirrhosis without HCC). Population controls were also considered. Odds ratios (ORs) associations were calculated using logistic regression, adjusting for age, sex, and principal components of genetic ancestry. Fixed-effect meta-analysis was used to determine the pooled effect size across all data sets. Across four case-control data sets, 2,070 HCC cases, 4,121 cirrhosis controls, and 525,779 population controls were included. The rs429358:C allele (APOE) was significantly less frequent in HCC cases versus cirrhosis controls (OR, 0.71; 95% confidence interval [CI], 0.61-0.84; P = 2.9 × 10-5 ). Rs187429064:G (TM6SF2) was significantly more common in HCC cases versus cirrhosis controls and exhibited the strongest effect size (OR, 2.03; 95% CI, 1.45-2.86; P = 3.1 × 10-6 ). In contrast, rs2792751:T (GPAM) was not associated with HCC (OR, 1.01; 95% CI, 0.90-1.13; P = 0.89), whereas rs2642438:A (MARC1) narrowly missed statistical significance (OR, 0.91; 95% CI, 0.84-1.00; P = 0.043). Conclusion: This study associates carriage of rs429358:C (APOE) with a reduced risk of HCC in patients with cirrhosis. Conversely, carriage of rs187429064:G in TM6SF2 is associated with an increased risk of HCC in patients with cirrhosis.

Differences in Glycemic Variability Between Normoglycemic and Prediabetic Subjects.

So far the criteria for NGT and abnormal glucose tolerance (AGT) are based on HbA1c and 75 g oGTT. We present data on GV and diurnal profiles in stratified cohorts with AGT versus controls. 28 NGT, 42 AGT (15 IGT, 11 IFG, 16 CGI) matched for age and BMI classified by 75 g oGTT underwent a CGM with test meal (TM). Diurnal profiles, glucose excursion after TM, and GV (SD, MAGE) were calculated for day 2 and 3. HbA1c, with its values of 5.5 ± 0.37% versus 5.65 ± 0.36%, was within normal range. Average interstitial glucose (AiG) was 5.84 ± 0.52 mmol/l) in NGT and 6.35 ± 0.65 mmol/l in AGT (P = .002). The 2 h incremental area under curve (iAUC) from TM until 2 h after TM was 1.94 ± 1.31 mmol/l*h versus 2.89 ( ± 1.75) mmol/l*h (P = .012), AiG 2 hours after TM was 5.99 ± 1.14 mmol/l*d versus 6.64 ± 1.30 mmol/l (P = .035). Peaks of AiG after TM were 7.69 ± 1.48 mmol/l*d versus 9.18 ± 1.67 mmol/l*d (P = .001). SD was significantly higher for AGT (1.12 ± 0.37 vs. 0.85 ± 0.32 mmol/l, P = .01) and MAGE 2.26 ± 0.84 vs. 1.60 ± 0.69 mmol/l, P = .005). In this comparative analysis NGT and AGT well matched for age, BMI, and comorbidities, CGM revealed significant differences in daytime AiG, pp glucose excursion and postprandial peaks. SD and MAGE was significantly higher for subjects with AGT. I Impaired glucose homeostasis a better characterizes degree of AGTe than HbA1c and 75 g OGTT.