Liver decompensation as late complication in HCC patients with long-term response following selective internal radiation therapy

Simple Summary: Hepatocellular carcinoma (HCC) is one of the deadliest forms of cancer. Selective internal radiation therapy (SIRT) is one of the therapeutic options for treatment of advanced HCC. Studies show that SIRT has a high objective response rate, but lack of survival benefit when compared to different treatment modalities. We hypothesized that this is due to potential damage in healthy liver parenchyma as a side-effect of SIRT, resulting in functional changes to the liver. This can ultimately result in liver decompensation and potentially death. The aim of this retrospective study was to assess long-term liver-related complications after SIRT in patients with HCC. We analyzed patients who underwent SIRT and found that liver decompensation occurred more often after SIRT when compared to sorafenib. However, careful patient selection may result in a survival benefit after SIRT when compared to other treatments. The ABLI score may be a valuable prognostic score for selecting patients.Selective internal radiation therapy (SIRT) is used as a treatment for hepatocellular carcinoma (HCC). The aim of this study was to assess long-term liver-related complications of SIRT in patients who had not developed radioembolization-induced liver disease (REILD). The primary outcome was the percentage of patients without REILD that developed Child-Pugh (CP) & GE; B7 liver decompensation after SIRT. The secondary outcomes were overall survival (OS) and tumor response. These data were compared with a matched cohort of patients treated with sorafenib. Eighty-five patients were included, of whom 16 developed REILD. Of the remaining 69 patients, 38 developed liver decompensation CP & GE; B7. The median OS was 18 months. In patients without REILD, the median OS in patients with CP & GE; B7 was significantly shorter compared to those without CP & GE; B7; 16 vs. 31 months. In the case-matched analysis, the median OS was significantly longer in SIRT-treated patients; 16 vs. 8 months in sorafenib. Liver decompensation CP & GE; B7 occurred significantly more in SIRT when compared to sorafenib; 62% vs. 27%. The ALBI score was an independent predictor of liver decompensation (OR 0.07) and OS (HR 2.83). After SIRT, liver decompensation CP & GE; B7 often developed as a late complication in HCC patients and was associated with a shorter OS. The ALBI score was predictive of CP & GE; B7 liver decompensation and the OS, and this may be a valuable marker for patient selection for SIRT.Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

Study protocol: adjuvant holmium-166 radioembolization after radiofrequency ablation in early-stage hepatocellular carcinoma patients-a dose-finding study (HORA EST HCC Trial)

Purpose To investigate the biodistribution of holmium-166 microspheres (Ho-166-MS) when administered after radiofrequency ablation (RFA) of early-stage hepatocellular carcinoma (HCC). The aim is to establish a perfused liver administration dose that results in a tumoricidal dose of holmium-166 on the hyperaemic zone around the ablation necrosis (i.e. target volume). Materials and Methods This is a multicentre, prospective, dose-escalation study in HCC patients with a solitary lesion 2-5 cm, or a maximum of 3 lesions of = 120 Gy has been reached on the target volume in 9/10 patients of a cohort. Secondary endpoints include toxicity, local recurrence, disease-free and overall survival. Discussion This study aims to find the optimal administration dose of adjuvant radioembolization with Ho-166-MS after RFA. Ultimately, the goal is to bring the efficacy of thermal ablation up to par with surgical resection for early-stage HCC patients.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Effects of the progestagen‐only contraceptive implant Implanon ®

Objective: Epidemiological studies on the cardiovascular risk of progestagen-only contraceptives are rare. With the present study we aimed to investigate the effect of the low-dose etonogestrel-releasing contraceptive implant Implanon® on cardiovascular risk factors, including markers of inflammation. Design: Longitudinal study. Setting: Family planning centre of a University Hospital. Subjects: Thirty-six healthy, nonsmoking women with regular cycles (n = 18 controls without hormonal contraception; n = 18 cases requesting the insertion of Implanon®). Measurements: Blood samples for the determination of C-reactive protein (CRP), nitric oxide (NO), sex hormones and plasma lipids were taken in the early follicular phase of the cycle in both groups. A second sample was taken 12 weeks after Implanon insertion or in the controls during the early follicular phase of cycle 4. Results: Implanon treatment caused a 36% decrease in CRP (P < 0·06) and a significant decrease in high density lipoprotein (HDL) (P < 0·007), low density lipoprotein (LDL) (P < 0·001), cholesterol (P < 0·001), testosterone (P < 0·05) and SHBG (P < 0·002). Levels of NO, oestradiol and progesterone were not affected in either group. The cholesterol/HDL ratio did not change in Implanon carriers. There was a significant correlation between the cardiovascular risk factors CRP, cholesterol/HDL ratio and NO. Conclusion: The progestagen-only implant Implanon does not exert a negative effect on the cardiovascular risk factors CRP, cholesterol/HDL ratio and NO. These results suggest that the use of a progestagen-only contraception does not increase cardiovascular risk factors in healthy young women

Pharmacodynamics and pharmacokinetics after repeated subcutaneous administration of three gonadotrophin preparations

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A comparison of recombinant human FSH (Puregon) and HMG in IVF cycles

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Characterizing Length Scales that Determine the Mechanical Behavior of gels from Crosslinked Casein Micelles

Mechanical behavior of a protein gel plays a large role in sensory properties. Despite the large amount of research on caseins, the origin of the mechanical behavior is not well understood yet. To determine the length scales that are relevant for the mechanical behavior of casein gels, casein micelles were crosslinked with increasing amount of transglutaminase followed by acidification to form gels. The gel heterogeneity, observed with confocal microscopy, electron microscopy and light scattering showed a gradual decrease on a micrometer length scale with increasing crosslinking. Such gradual change as a function of crosslinking was also observed in the elastic modulus and the Young’s modulus of the gels. Furthermore, particle size both prior to gelation and in the gel decreased with increasing crosslinking. Casein micelle stiffness (determined by atomic force microscopy) showed a maximum and the amount of water entrapped by the gel particles and their aggregates in the gel (determined by neutron scattering) showed a minimum with increasing crosslinking. These extrema coincides with the extrema observed in kinetics of gel formation and in gel breakdown properties. It was concluded that the elasticity of the gel originates on the length scale of the casein micelle (a few hundred nanometer), while fracture properties are determined at a smaller length scale, by the structure within the casein micelle

High dose gonadotrophin-releasing hormone antagonist (ganirelix) may prevent ovarian hyperstimulation syndrome caused by ovarian stimulation for in-vitro fertilization

This case report describes the first attempt to treat imminent ovarian hyperstimulation syndrome (OHSS) by using a gonadotrophin-releasing hormone (GnRH) antagonist. A 33 year old, normo-ovulatory woman undergoing in-vitro fertilization received daily subcutaneous injections of 150 IU of recombinant follicle-stimulating hormone (recFSH) from cycle day 2, together with GnRH antagonist (ganirelix) 0.125 mg from cycle day 7 onwards. On cycle day 10 the patient was found to have a serum oestradiol concentration of 16 500 pmol/l and, on ultrasound examination, four preovulatory (&gt;16 mm) and nine intermediate sized (10-16 mm) follicles. RecFSH injections were discontinued, human chorionic gonadotrophin (HCG) withheld, whereas the ganirelix dose was increased to 2 mg/d. This regimen led to a rapid decrease in serum oestradiol concentrations and the decrease in ovarian size on ultrasound. Since GnRH antagonists will become clinically available for in-vitro fertilization programmes in the near future this suggested regimen might have a role in preventing severe OHSS

Follicular development after 7-days subcutaneous administration of Normegon, Follegon and Metrodin-HP

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