1A) PH abruptly reduced hepatic expression of Hip, and Hip mRNA

1A). PH abruptly reduced hepatic expression of Hip, and Hip mRNA levels generally remained below pre-PH values during the prereplicative, replicative, and postreplicative periods after PH. Reduced Hip expression was accompanied by increased expression of Hh ligands. Messenger RNA levels of Ihh began to increase during the CDK inhibitors in clinical trials prereplicative period, remained at their highest values during the replicative period, then gradually declined. Expression of Shh did not increase until the middle to the end of the replicative

period but remained high throughout the postreplicative period after PH. The relative abundance of Ptc and Smo mRNAs changed after PH, such that expression of Smo (the signaling competent Hh co-receptor) was greater than that of Ptc (the inhibitory Hh receptor) throughout the replicative and postreplicative periods. Together with the reciprocal changes in mRNA expression of Hh ligand antagonists and Hh ligands, the predominance of Smo relative to Ptc suggested that Hh signaling would increase after PH. Changes in expression of Gli1 and Gli2 support this concept. Levels of Gli1

began to increase in the prereplicative BI 6727 clinical trial period and remained at high levels until the end of the postreplicative period. Increases in Gli1 expression were followed by increases in mRNA levels of Gli2, a Gli-regulated gene.20 Gli2 expression began to increase during the replicative period, peaked somewhat later, and then remained high throughout the

postreplicative period. Increased Gli1 and Gli2 mRNA levels were accompanied by increased levels of Gli1 and Gli2 proteins at 48 hours post-PH (the time point of maximal mRNA expression of these genes during the replicative period) (Fig. 1B), and followed by increased mRNA expression of secreted frizzled-related protein 1 (sFRP1), a Gli-regulated, Hh-target gene (Fig. 1C).25 Hence, PH led to dramatic increases in Hh signaling, particularly during the intervals when liver cell replication and remodelling responses are known to occur in the regenerating liver tissues. During chronic liver injury, Hh pathway activation promotes accumulation of liver epithelial progenitor cells and myofibroblasts and stimulates fibrogenic repair. Hepatic expression of progenitor markers, such as AFP 上海皓元 and Fn14, increase after PH.8, 9 We confirmed these observations (Fig. 2). Fn14 increased 40-fold during the early prereplicative period and remained at least fivefold above basal values throughout the entire postreplicative period, although expression of the Fn14 ligand, tumor necrosis factor-like weak inducer of apoptosis (TWEAK), remained relatively constant after PH. Early increases in Fn14 were followed by increases in AFP expression, which peaked sharply (at 160-fold above basal values) late in the replicative period (Fig. 2A). Hepatic progenitor populations are known to be heterogeneous.

1A) PH abruptly reduced hepatic expression of Hip, and Hip mRNA

1A). PH abruptly reduced hepatic expression of Hip, and Hip mRNA levels generally remained below pre-PH values during the prereplicative, replicative, and postreplicative periods after PH. Reduced Hip expression was accompanied by increased expression of Hh ligands. Messenger RNA levels of Ihh began to increase during the JQ1 mw prereplicative period, remained at their highest values during the replicative period, then gradually declined. Expression of Shh did not increase until the middle to the end of the replicative

period but remained high throughout the postreplicative period after PH. The relative abundance of Ptc and Smo mRNAs changed after PH, such that expression of Smo (the signaling competent Hh co-receptor) was greater than that of Ptc (the inhibitory Hh receptor) throughout the replicative and postreplicative periods. Together with the reciprocal changes in mRNA expression of Hh ligand antagonists and Hh ligands, the predominance of Smo relative to Ptc suggested that Hh signaling would increase after PH. Changes in expression of Gli1 and Gli2 support this concept. Levels of Gli1

began to increase in the prereplicative www.selleckchem.com/products/BIBW2992.html period and remained at high levels until the end of the postreplicative period. Increases in Gli1 expression were followed by increases in mRNA levels of Gli2, a Gli-regulated gene.20 Gli2 expression began to increase during the replicative period, peaked somewhat later, and then remained high throughout the

postreplicative period. Increased Gli1 and Gli2 mRNA levels were accompanied by increased levels of Gli1 and Gli2 proteins at 48 hours post-PH (the time point of maximal mRNA expression of these genes during the replicative period) (Fig. 1B), and followed by increased mRNA expression of secreted frizzled-related protein 1 (sFRP1), a Gli-regulated, Hh-target gene (Fig. 1C).25 Hence, PH led to dramatic increases in Hh signaling, particularly during the intervals when liver cell replication and remodelling responses are known to occur in the regenerating liver tissues. During chronic liver injury, Hh pathway activation promotes accumulation of liver epithelial progenitor cells and myofibroblasts and stimulates fibrogenic repair. Hepatic expression of progenitor markers, such as AFP MCE公司 and Fn14, increase after PH.8, 9 We confirmed these observations (Fig. 2). Fn14 increased 40-fold during the early prereplicative period and remained at least fivefold above basal values throughout the entire postreplicative period, although expression of the Fn14 ligand, tumor necrosis factor-like weak inducer of apoptosis (TWEAK), remained relatively constant after PH. Early increases in Fn14 were followed by increases in AFP expression, which peaked sharply (at 160-fold above basal values) late in the replicative period (Fig. 2A). Hepatic progenitor populations are known to be heterogeneous.

Methods: From a prospective database of patients undergoing HRM (

Methods: From a prospective database of patients undergoing HRM (N), those with dysphagia and normal EGD (n) were BMS-907351 in vitro included. Study period – 24 months (April 2012

– March 2014). HRM was performed using 16-channel water perfusion based system and data was analyzed using unique Trace™ software. Chicago classification was used for reporting and nomenclature. Results: N = 310, n = 78 (25.1%), M: F – 42 : 36 (1.17: 1), mean age – 45 years (range 19–80). Manometry findings: achalasia cardia (AC) – 33 (42%), non-specific motility disorder with focal peristaltic failure – 11 (14.1%), ineffective esophageal motility – 6 (7.7%), nutcracker esophagus – 5 (6.4%), diffuse esophageal spasm – 3 (3.8%), neuromuscular dysphagia related buy Trichostatin A to UES – 2 (2.6%), normal HRM – 8 (10.3%). AC group – subtype – Type 1–4 (12%), Type 2–25 (76%), Type 3–4 (12%). M: F ratio (Types 1, 2 and 3) – 1: 1, 3: 1, 1.2: 1 respectively. 10 patients underwent pre and post POEM HRM. All showed post procedure reduction in basal LES pressure. Conclusion: HRM has high sensitivity (90%) to diagnose motility disorders in patients with dysphagia and normal EGD. Achalasia cardia was the commonest disorder in our study. Key Word(s): 1. manometry; 2. high resolution manometry; 3. oesophageal motility disorder; 4. achalasia cardia; 5. dysphagia Presenting Author: MADHUSUDAN SAHA Additional Authors: KAMRUN

NAHAR, IRIN PARVEEN, M M ARIF HOSEN, M H KHAN, MD JAHANGIR ALAM, SYED ALAMGIR SAFWATH Corresponding Author: MADHUSUDAN SAHA Affiliations: Centre of Nuclear Medicine And Ultrasound, Enam Medical College, Savar, Dhaka, Centre of Nuclear Medicine And Ultrasound, Centre medchemexpress of Nuclear Medicine And Ultrasound, Sylhet M A G Osmani Medical College, Sylhet M A G Osmani Medical College Objective: This hospital-based study was done to see the prevalence of sonologically detected non alcoholic fatty liver

disease and associated factors in the apparently healthy adult population. Methods: Apparently healthy and non alcoholic company of the patients visiting the Centre of Nuclear Medicine and ultrasound, Sylhet were subjected to abdominal ultrasonography to see the presence of fatty liver. Demographic features and other relevant data were collected in a semi structured questionnaire to find out the associated factors for NAFLD. Results: Total 1019 persons with mean age of 37.23 years were included in the study. Among them 703 (69%) were female and 316 (31%) were male. Out of them 189 (18.5%) persons had sonologically detectable nonalcoholic fatty liver disease. NAFLD was more prevalent in male than female (25.6% vs. 15.4%, P 0.000). In univariate analysis NAFLD were more. Conclusion: Sonologically detected nonalcoholic fatty liver disease (18.5%) is common in our apparently healthy adults. BMI over 23 kg/m 2 was the most important predictor for NAFLD. Key Word(s): 1. sonologically detected non-alcoholic fatty liver disease; 2.

The aim of this study is to determine listing practices for morbi

The aim of this study is to determine listing practices for morbidly obese

patients in United States (U.S.) liver transplant centers. Methods: A 19 item survey was created to assess liver transplant evaluation and listing practices for morbidly obese patients. All U.S. adult liver transplant medical and surgical directors were contacted by email with a cover letter describing the study and an internet link to the SurveyMonkey® website. A few questions had a free-text section which allowed for comment. Five follow-up emails were sent to encourage participation. Results: A total of 187 surveys were emailed with responses received from 46 physicians (24.7% response rate). The responding cohort Selleck AZD9668 consisted of 29 (63%) medical directors and 17 (37%) surgical directors, including respondents from all United Network Organ Sharing (UNOS) regions, though regions 4 and 6 had the fewest respondents (n=2). The majority of respondents reported treating patients at an academic medical center (73.3%) and performing more than 50 liver transplants a year (60.8%). A policy on evaluation and listing of obese patients

was present at 70.5% of institutions with the majority (54.5%) reporting their BMI cut off for transplant was 40 but a range of 35 to unlimited was noted. The majority (61.4%) of Ibrutinib datasheet respondents agreed that there has been an increase in the number of obese patients they have listed for liver transplant, however 75% of

respondents’ reported medchemexpress that patients with high BMI were less likely to be evaluated for transplantation. With regards to complications in obese patients, 65.9% of respondents reported experiencing an increased complication rate, with the most frequently cited complications being poor wound healing and increased infection rates. Despite the reported increased complication rate, only 34.1% reported they had experienced worse survival rates with obese patients. Conclusions: The majority of medical and surgical liver transplant directors have a strong appreciation of the possible morbidity risks associated with morbidly obese patients post-transplant and have policies in effect to minimize these risks. This is of specific concern due to the need to provide more high quality and cost effective transplant care in the current healthcare climate. More data examining morbidly obese cirrhotic patient outcomes perioper-atively, stratified by other co-morbidities, is needed. Disclosures: Jonathan M. Fenkel – Consulting: Gilead Pharmaceuticals, Janssen Therapeutics The following people have nothing to disclose: Dina Halegoua-De Marzio, She-Yan Wong, Cataldo Doria, David A. Sass Background: Racial/ethnic disparities in liver transplantation (LT) are well established. African Americans (AAs) are referred for LT at lower rates, and there is significantly lower post-LT survival among AAs compared to other groups.

The principle of the technology is based on detecting hydrogen io

The principle of the technology is based on detecting hydrogen ions released in the reaction-induced changes of the pH

of the solution by an ion sensor when the nucleotide base is incorporated by DNA polymerase. Its read length of approximately PLX3397 100 bp is comparable to that of other NGS systems, but the throughput is still lower, although increasing the size of the semiconductor chips could improve the throughput.[19, 20] Pacific Biosciences (PacBio, Menlo Park, CA, USA) developed a single molecule real-time sequencer based on single molecule real-time sequencing by the synthesis method with monitoring of the deoxyribonucleotide triphosphate (dNTP) uptake of DNA sequencing by DNA polymerase. The fluorescently labeled dNTP is incorporated and the fluorescent dye is separated from the DNA. The sequencing reaction is conducted on zero-mode wave guides (ZMW) that are small well-containers with detectors located at the bottom of the well. The detectors can capture the fluorescent dye. The DNA polymerase is immobilized

by only one molecule at the bottom. After the single template DNA is bound to the polymerase with incorporation of the fluorescently labeled dNTP, the DNA synthesis is performed. The DNA sequencing is conducted by detecting the separated fluorescent dye.[21] In January 2011, a paper from PacBio was published in the New England Journal of Medicine Lenvatinib cost demonstrating the origin of the 2010 cholera outbreak in Haiti.[22] The PacBio RS was commercially released in early 2011 and had the advantage of a short time from equipping the library to sequencing, obtaining long reads and fewer errors or bias with PCR amplification. However, there is the disadvantage of low yield at high accuracy and low throughput. Nanopore sequencing technology has been developing since 1995 for determining

the sequence without nucleotide labeling and detection.[23] In brief, DNA sequencing with nanopore technology relies on the conversion of the electrical signals of nucleotides by passing through a nanopore, which is a specific protein pore covalently attached to the molecules. This approach is the most advanced and was demonstrated by Oxford Nanopore Technologies (Oxford Science Park, Oxford, UK).[24] Two nanopore sequencer models, the GridION sequencer which can perform large-scale sequencing, and the MinION sequencer, which is a portable and MCE公司 disposable sequencer, are planned for release. The MinION sequencer is a breakthrough device that overturns the concept of previous sequencers. The size of this sequencer is almost the same as a Universal Serial Bus (USB) memory stick and, after plugging this sequencer into the USB port of a personal computer, sequencing can be performed just by loading the sample. So far, this nanopore sequencer has tremendously surpassed other NGS systems. But there is a problem in that the error rate is still high compared with the Illumina or SOLiD sequencers.

Inhibitor development, because of its impact on patients’ morbidi

Inhibitor development, because of its impact on patients’ morbidity and quality of life, is presently the most serious complication of haemophilia A treatment. The Daporinad clinical trial identification of several

genetic and non-genetic risk factors may be used for the stratification of inhibitor risk and the definition of prevention strategies, particularly for patients with a high-risk genetic profile. The most extensively studied genetic factor is the type of F8 mutation, i.e. large deletions, nonsense mutations and inversions, which are associated with a higher risk of inhibitor development. This is the basis for the increased risk in patients

with inhibitor family history; however, concordance family studies showed that factors other than F8 mutations are involved. An emerging role is investigated for polymorphisms of immune-regulatory genes that may increase (IL-10 and TNF-α) or reduce (CTLA-4) inhibitor risk and whose heterogeneous ethnic distribution may correlate to Midostaurin molecular weight the higher inhibitor risk in non-caucasian patients. A role for FVIII haplotypes, particularly in black haemophiliacs, has been recently proposed. Recent studies report an increased inhibitor risk for initial intensive treatments (surgery or severe bleeds requiring high-dose and/or prolonged treatment, presence of danger signals),

whereas regular prophylaxis (absence of danger signals) exerts a protective effect. A clinical 上海皓元 score including the type of F8 mutation, family history of inhibitors and intensive treatment has been recently validated for predicting inhibitor risk. Because of the lack of useful data regarding the role of different types of FVIII concentrates, the stratification of risk in patients starting replacement treatment together with the careful evaluation of indications, doses and duration of treatment at first exposures and further efforts for overcoming barriers to early implementation of prophylaxis are encouraged, particularly for patients with a predictable high inhibitor risk. Approximately 30% of severe haemophilic patients generates antibodies (inhibitors) against therapeutically administered factor VIII (FVIII), typically during the first 20 exposure days (ED) [1]. Inhibitor development remains the most serious and challenging complication of modern treatment of haemophilia A in developed countries [2], where safe FVIII concentrates are largely available and where prophylaxis is increasingly used to prevent arthropathy.

Following maturation and toxicology studies we aim for a Phase 1

Following maturation and toxicology studies we aim for a Phase 1 clinical trial. Key Word(s): 1. Antibody ; 2. Immunotoxin; 3. Antibody derivatives; 4. Humanization; Presenting Author: GUIZHEN XIAO Additional Authors: YALI ZHANG Corresponding Author: Navitoclax solubility dmso YALI ZHANG Affiliations: Department of Gastroenterology, Nanfang Hospital, Southern Medical University; Department of Gastroenterology, Nanfang Hospital, Southern Medical University Objective: Dysfunction of the intestinal epithelial tight junction (TJ) barrier is known to have an important

etiologic role in the pathophysiology of heat stroke. N-3 polyunsaturated fatty acids (PUFAs), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), play a role in maintaining and protecting the TJ structure and function. This study is aimed at investigating whether n-3 PUFAs could alleviate heat stress-induced dysfunction of intestinal tight junction. Methods: Human

Fostamatinib intestinal epithelial Caco-2 cells were pre-incubated with EPA, DHA or arachidonic acid (AA, n-6 PUFA) and then exposed to heat stress. Transepithelial electrical resistance (TEER) and Horseradish Peroxidase (HRP) permeability were measured to analyze barrier integrity. Levels of TJ proteins, occludin and ZO-1, were analyzed by Western blot and localized by immunofluorescence microscopy. Messenger RNA levels were determined by quantitative real time polymerase chain reaction (Q-PCR). TJ morphology was observed by transmission electron microscopy. Results: EPA effectively attenuated the decrease in TEER and impairment of intestinal permeability in HRP flux induced by heat exposure. The amount of occludin and ZO-1

significantly decreased at 43°C, although occludin increased at 41°C. The expression of occludin and ZO-1 was significantly elevated by EPA, while DHA was less effective and AA was no effective. The distortion and redistribution of TJ proteins, and disruption of morphology were also effectively prevented by pretreatment with EPA. Conclusion: This study indicates for the first time that EPA is more potent than DHA in protecting against heat-induced permeability dysfunction and epithelial barrier damage of tight junction. Key Word(s): MCE公司 1. EPA; 2. DHA; 3. Epithelial Barrier; Presenting Author: GABRIEL GRAU Additional Authors: ALEXIA TORRES, PEDRO ASO, ELENA MYLONÁS, GLADINEX PERÉZ, FABIOLA FABIANO Corresponding Author: GABRIEL GRAU Affiliations: IDID; USB; Professor Objective: In many regions the leguminous represent the only source of protein in the diet, this together with the growing interest in obtaining novel sources of proteins, the determination of its allergenic potential have become a need. Allergic reactions to some leguminous proteins are well known and are associated with globulins 7 and 11 Svedberg (S). In Venezuela the use of leguminous flours as pigeon pea (Cajanus cajan), have been increased.

2 Angulo P et al The NAFLD fibrosis score: a non-invasive syste

2. Angulo P et al. The NAFLD fibrosis score: a non-invasive system that identifies liver fibrosis in patients with NAFLD. Hepatology 2007;45:846–854. M VEYSEY,1,2,3 W SIOW,1,2 S NIBLETT,2,3 K KING,2,3 Z YATES,4 M LUCOCK5 1Department of Gastroenterology and 2Teaching & Research Unit, Central Coast Local Health District and the 3Schools of Medicine & Public Health, 4Biomedical Sciences and 5Environmental & Life Sciences, University of Newcastle, NSW, Australia Introduction: An elevated white cell count is associated with both metabolic syndrome and insulin resistance, with non-alcoholic fatty liver disease (NAFLD) being considered the hepatic manifestation of metabolic

syndrome. There are limited data suggesting an association between raised peripheral white cell counts and NAFLD. The fatty liver index (FLI)1 is a validated, non-invasive method of estimating the VX809 likelihood of NAFLD in individuals and is calculated using

an algorithm that incorporates 4 parameters: BMI, waist circumference, GGT and triglyceride levels. We, therefore, set out to examine the relationship between NAFLD, defined as an FLI≥60, and peripheral white cell counts. Methods: We used a prospectively recruited population of 440 community-based participants, aged over 65 (mean age 78 yr, 264 females), who completed a comprehensive assessment of their medical history, metabolic risk factors, medications Tyrosine Kinase Inhibitor Library datasheet and alcohol intake. Patients with other liver disease or alcohol intake >20.5 g/day were excluded. All subjects had their FLIs calculated and were classified into three groups, FLI < 30 (No NAFLD), 30

≤ FLI < 60 (Borderline) and FLI ≥ 60 (NAFLD). White cell counts and differentials were measured in peripheral blood collected at the time of FLI estimation. Results: No NAFLD NAFLD p value n = 122 N = 190 White cell count (109/l) 5.89 ± 1.64 6.83 ± 1.66 medchemexpress <0.001 Neutrophils (109/l) 3.47 ± 1.29 4.03 ± 1.19 <0.001 Lymphocytes (109/l) 1.69 ± 0.67 1.97 ± 0.81 <0.01 Monocytes (109/l) 0.51 ± 0.17 0.56 ± 0.17 <0.01 Eosinophils (109/l) 0.19 ± 0.16 0.23 ± 0.16 <0.05 Basophils (109/l) 0.02 ± 0.04 0.02 ± 0.05 ns For the whole cohort, there were weak but significant linear relationships between FLI and white cell count (r = 0.25, p < 0.001), neutrophils (r = 0.20, p < 0.001), lymphocytes (r = 0.17, p < 0.001), monocytes (r = 0.15, p < 0.01) and eosinophils (r = 0.12, p < 0.05). Furthermore, there was a linear relationship between FLI and CRP (r = 0.14, p < 0.01), supporting the inflammatory nature of NAFLD. Conclusion: This study confirms that NAFLD is associated with elevation of peripheral white cell counts and supports the inflammatory nature of NAFLD. That all sub-types of white cell, except basophils, are elevated in NAFLD suggests that the inflammatory process may be multifactorial. 1. Koehler E et al. External Validation of the Fatty Liver Index for Identifying Non-alcoholic Fatty Liver Disease in a Population-based Study.

Based on the FDG uptake pattern, sensitivity, specificity, positi

Based on the FDG uptake pattern, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for FDG-PET/CT in characterizing the periampullary and pancreatic masses into benign and malignant lesions were 93%, 90%, 95%, 87%, and 92% respectively. Receiver operating characteristics curve analysis of the SUVmax of the lesions yielded a cut-off value of 2.8, with a sensitivity and specificity of 87.5% and 45% respectively. The FDG uptake pattern in PET/CT can differentiate malignant from benign mass-forming

lesions of the pancreas with high accuracy and a discrete cut-off value of SUVmax could Sirolimus manufacturer not be defined for the same as even lesions with pancreatic tuberculosis showed very high FDG uptake. Hence, in patients with a suspicion of malignancy in the pancreas, a focally increase FDG uptake in PET/CT suggests the diagnosis of malignancy.


“Angiopoietin-like protein 2 (ANGPTL2) plays various roles in metabolism, vascular biology, inflammation and tumor metastasis, but little is known about its function in human hepatocellular carcinoma metastasis. This study aimed to further explore the function of ANGPTL2 on migration and invasion Linsitinib mw of liver cancer cells. Quantitative real time polymerase chain reaction (qRT-PCR), western blotting, immunohistochemistry, transwell migration and invasion assays were performed to clarify the function of ANGPTL2 in the regulation of cell migration and invasion MCE in human hepatocellular carcinoma (HCC). In HCC patients, ANGPTL2 expression was higher in HCC tissues compared with matched noncancerous liver tissues. And the ANGPTL2 levels of HCC tissues positively correlated with intrahepatic metastasis in HCC patients. Overexpression of ANGPTL2 significantly increased migration and invasion of HCC cells in vitro and promoted intrahepatic

and distal pulmonary metastasis in vivo, while knockdown of endogenous ANGPTL2 resulted in a reduced migration and invasion in vitro. Colony formation assay and MTT assay showed ANGPTL2 did not affect cell proliferation in vitro, whereas overexpression of ANGPTL2 promoted tumor formation in xenograft animal model. Our findings show that ANGPTL2 drives human HCC metastasis and provides a potential therapeutic target for HCC treatment. “
“Aim:  Chronic ethanol exposure impairs insulin signaling in the liver. Peroxisome-proliferator activated receptor (PPAR) agonists function as insulin sensitizers and are used to treat type 2 diabetes mellitus. We examined the therapeutic effectiveness of PPAR agonists in reducing alcoholic hepatitis and hepatic insulin resistance in a model of chronic ethanol feeding. Methods:  Adult male Long Evans rats were pair fed with isocaloric liquid diets containing 0% (control) or 37% ethanol (caloric content; 9.2% v/v) for 8 weeks. After 3 weeks on the diets, the rats were treated with vehicle, or a PPAR-α, PPAR-δ or PPAR-γ agonist twice weekly by i.p.

7 The main radioactive agent integrated with microspheres for rad

7 The main radioactive agent integrated with microspheres for radioembolization or selective internal radiotherapy (SIRT) is yttrium-90 (Y-90), although other agents have been reported. To date, two products for radioembolization with Y-90 microspheres are commercially available, based on resin or glass. Due to a smaller size and a significantly higher amount of radioactivity per single sphere,8 glass microspheres do not show embolizing effects on larger tumor vessels. This limits exposure to surrounding liver tissue and allows glass microspheres to be utilized

in the presence of portal vein thrombosis.7 We report the analysis of 108 consecutive cases with intrahepatic advanced HCC treated with Y-90 glass microsphere radioembolization. The Linsitinib aim of this study was to provide evidence on the safety of this therapy CH5424802 solubility dmso in this particular group of patients and to determine long-term survival, which has to be considered the most significant clinical endpoint. AE, adverse event; AFP, alphafetoprotein; BCLC, Barcelona Clinic Liver Cancer; HCC, hepatocellular carcinoma; MAA, macroaggregated albumin;

PVT, portal vein thrombosis; RECIST, Response Evaluation Criteria in Solid Tumors; SIRT, selective internal radiotherapy; SPECT, single photon emission computed tomography; TACE, transarterial chemoembolization; Phospholipase D1 Tc-99, technetium-99; TTP, time to progression; RILD, radiation-induced liver disease; Y-90, yttrium-90. In all, 108 consecutive patients with advanced HCC who were treated with radioembolization with Y-90 glass microspheres at a single center (University Hospital Essen, Germany) between November 2006 and March 2009 were included in this observational

cohort study. The indication for Y-90 treatment was driven by an institutional algorithm based on the BCLC treatment scheme. Patients were routinely staged by a 3-phase computed tomography (CT) or magnetic resonance imaging (MRI) of the liver, a contrast-enhanced ultrasound to further determine vascularity, as well as a CT of the lungs. If alphafetoprotein (AFP) was >400 ng/mL, patients additionally received a technetium-99 (Tc-99)-based bone scan. The major clinical features allowing Y-90 treatment and therefore inclusion into this observational study were nonresectability of HCC and BCLC C tumor stage. Patients with BCLC A and B were also included if they were not eligible for selective TACE. Additional inclusion criteria were adequate hypervascularity (concentration and consecutive “blush” of contrast agent in the arterial phase of CT and/or contrast-enhanced ultrasound), a liver function with a Child-Turcotte-Pugh (CTP) score ≤7 points, and an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.