Summary
Background
It remains unclear whether initial compact lipiodol uptake after transarterial chemoembolisation (TACE) is associated with improved survival in patients with hepatocellular ...carcinoma (HCC).
Aim
To reveal the clinical relevance of compact lipiodolisation after TACE.
Methods
We studied 490 patients with unresectable HCC who had first been treated with TACE. Compact lipiodolisation was defined as the absence of an arterial enhancing lesion, reflecting complete lipiodol uptake, as assessed by dynamic computed tomography (CT) 1 month after treatment. The rate of initial compact lipiodolisation was analysed according to multiplicity and size of tumour, and survival of patients who achieved compact lipiodolisation was compared to that of patients who did not.
Results
Of the 490 patients, 409 (83.5%) were in Child–Pugh class A and 81 (16.5%) in class B. The rate of initial compact lipiodolisation in single HCCs was higher than that in multinodular HCCs (33.7% vs. 14.6%, P < 0.001). Among single HCCs, the rate of compact lipiodolisation in tumours ≤5, 5–10 and >10 cm was 46.6%, 13.6%, and 0% respectively. The 1‐, 3‐ and 5‐year survival rates of patients with compact uptake were 92.7%, 70.7% and 52.4% compared to 60.8%, 28.0% and 16.9% in patients with noncompact lipiodolisation. Multivariate analysis revealed that Child–Pugh class, alpha‐fetoprotein level, tumour node metastasis stage, portal vein thrombosis and initial compact lipiodolisation were independent predictors of survival.
Conclusions
Initial compact lipiodol uptake after transarterial chemoembolisation is associated with improved survival in patients with unresectable hepatocellular carcinoma. Accordingly, initial complete lipiodolisation should be considered a relevant therapeutic target.
Activated hepatic stellate cells (HSCs) but not quiescent HSCs express cyclo-oxygenase-2 (COX-2), suggesting that the COX-2/prostanoid pathway has an active role in hepatic fibrogenesis. However, the ...role of COX-2 inhibitors in hepatic fibrogenesis remains controversial. The aim of this study was to investigate the antifibrotic effects of celecoxib, a selective COX-2 inhibitor.
The effects of various COX inhibitors-that is, ibuprofen, celecoxib, NS-398 and DFU, were investigated in activated human HSCs. Then, the antifibrotic effect of celecoxib was evaluated in hepatic fibrosis developed by bile duct ligation (BDL) or peritoneal thioacetamide (TAA) injection in rats.
Celecoxib, NS-398 and DFU inhibited platelet-derived growth facor (PDGF)-induced HSC proliferation; however, only celecoxib (> or =50 microM) induced HSC apoptosis. All COX inhibitors completely inhibited prostaglandin E(2) (PGE(2)) and PGI(2) production in HSCs. Separately, PGE(2) and PGI(2) induced cell proliferation and extracellular signal-regulated kinase (ERK) activation in HSCs. All COX inhibitors attenuated ERK activation, but only celecoxib significantly inhibited Akt activation in HSCs. Celecoxib-induced apoptosis was significantly attenuated in HSCs infected with adenovirus containing a constitutive active form of Akt (Ad5myrAkt). Celecoxib had no significant effect on PPARgamma (peroxisome proliferator-activated receptor gamma) expression in HSCs. Celecoxib inhibited type I collagen mRNA and protein production in HSCs. Oral administration of celecoxib (20 mg/kg/day) significantly decreased hepatic collagen deposition and alpha-SMA (alpha-smooth muscle actin) expression in BDL- and TAA-treated rats. Celecoxib treatment significantly decreased mRNA expression of COX-2, alpha-SMA, transforming growth factor beta1 (TGFbeta1) and collagen alpha1(I) in both models.
Celecoxib shows a proapoptotic effect on HSCs through Akt inactivation and shows antifibrogenic effects in BDL- and TAA-treated rats, suggesting celecoxib as a novel antifibrotic agent of hepatic fibrosis.
Current treatment guidelines suggest that antiviral therapy be considered for chronic hepatitis B (CHB) patients with high viral load if a biopsy shows significant liver disease despite alanine ...aminotransferase (ALT) levels two times or less than the upper limit of normal (ULN). We evaluated the histological findings in CHB patients with high viral load and persistently normal or slightly elevated serum ALT levels. Between January 2003 and June 2006, 105 consecutive treatment‐naive patients with CHB who underwent ultrasonography‐guided percutaneous liver biopsy, had detectable serum HBV DNA (>105 copies/mL) in a direct hybridization assay and normal or slightly elevated serum ALT levels (≤2 × ULN) for at least 12 months were included in a prospective study. Histological assessment was based on the METAVIR scoring system. Significant histology was defined as fibrosis stage ≥F2 or necroinflammation grade ≥A2. Among the 105 CHB patients with high viral load and persistently normal or slightly elevated serum ALT levels for at least 12 months, significant fibrosis (F2–F4 fibrosis) was observed in 63 patients (60.0%) and the actual significant histology was found in 65 patients (61.9%). On multivariate analysis, serum ALT levels and age at which they entered the study were independent factors associated with significant histology. Odds ratios for significant histology increased progressively according to serum ALT levels and age. In conclusion, a large proportion of CHB patients with genotype C, high viral load and ALT ≤2 × ULN had significant liver disease on liver biopsy and should be considered for antiviral therapy.
Exposure to polycyclic aromatic hydrocarbons (PAHs) associated with ambient air particulate matter (PM) poses significant health concerns. Increased acute exacerbation (AE) frequency in asthmatic ...patients has been associated with ambient PAHs, but which subgroup of patients are particularly susceptible to ambient PAHs is uncertain. We developed a new model to simulate grid-scale PM
-PAH levels in order to evaluate whether the severity of asthma as measured by the Global Initiative of Asthma (GINA) levels of treatment is related to cumulative exposure of ambient PAHs.
Patients with asthma residing in the northern Taiwan were reviewed retrospectively from 2014 to 2017. PM
were sampled and analysed for PAHs twice a month over a 72-hour period, in addition to collecting the routinely monitored air pollutant data from an established air quality monitoring network. In combination with correlation analysis and principal component analysis, multivariate linear regression models were performed to simulate hourly grid-scale PM
-PAH concentrations (ng/m
). A geographic information system mapping approach with ordinary kriging interpolation method was used to calculate the annual exposure of PAHs (ng/m).
Among the 387 patients with asthma aged 18 to 93 (median 62), 97 subjects were treated as GINA step 5 (24%). Asthmatics in GINA 5 subgroup with high annual PAHs exposure were likely to have a higher annual frequency of any AE (1 (0-12), p<0.0001). Annual PAHs exposure was correlated with the annual frequency of any exacerbation (r=0.11, p=0.02). This was more significant in the GINA 5 subgroup (r=0.29, p=0.005) and in the GINA 5 subgroup with severe acute exacerbations (r=0.51, p=0.002). Annual PAHs exposure, severe acute exacerbation and GINA steps were independent variables that predict annual frequency of any exacerbation.
Asthmatic patients in the GINA 5 subgroup with acute exacerbations were more susceptible to the effect of environmental PAHs on their exacerbation frequency. Reducing environmental levels of PAHs will have the greatest impact on the more severe asthma patients.
We present observations and analysis of a sample of 123 galaxy clusters from the 2013 Planck catalogue of Sunyaev-Zel’dovich sources with the Arcminute Microkelvin Imager (AMI), a ground-based radio ...interferometer. AMI provides an independent measurement with higher angular resolution, 3 arcmin compared to the Planck beams of 5–10 arcmin. The AMI observations thus provide validation of the cluster detections, improved positional estimates, and a consistency check on the fitted size (θs) and flux (Ytot) parameters in the generalised Navarro, Frenk and White (GNFW) model. We detect 99 of the clusters. We use the AMI positional estimates to check the positional estimates and error-bars produced by the Planck algorithms PowellSnakes and MMF3. We find that Ytot values as measured by AMI are biased downwards with respect to the Planck constraints, especially for high Planck-S/N clusters. We perform simulations to show that this can be explained by deviation from the universal pressure profile shape used to model the clusters. We show that AMI data can constrain the α and β parameters describing the shape of the profile in the GNFW model for individual clusters provided careful attention is paid to the degeneracies between parameters, but one requires information on a wider range of angular scales than are present in AMI data alone to correctly constrain all parameters simultaneously.
Growing evidence suggests that interleukin-18 (IL-18) levels may affect neoplasia and that single nucleotide polymorphisms (SNPs) within IL-18 gene may influence its production. In this study, we ...evaluated whether IL-18 and IL-18 receptor (IL-18R) polymorphisms are associated with the development and clinicopathological features of papillary thyroid carcinoma (PTC).
Using direct sequencing, we investigated the association between functional polymorphisms of IL-18 and IL-18R genes and susceptibility to PTC in 94 PTC patients and 260 healthy controls. Genetic data were analyzed using commercially available software. Multiple logistic regression models were used to calculate odds ratios, 95% confidence intervals, and P-values for the association between the genotypes and risk of PTC. The PTC patients were further subgrouped and compared with respect to their clinicopathological characteristics.
3 SNPs of IL-18 (rs549908, rs360717, and rs187238) and one of IL-18R (rs1420106) examined in this study were significantly associated with the development of PTC. The allelic frequencies of the 3 SNPs of IL-18 also showed significant association with lymph node metastasis.
IL-18 and IL-18R polymorphisms may contribute to the development and lymph node metastasis of PTC.
Although the mechanism of susceptibility to chronic persistent hepatitis B virus (HBV) infection is not well clarified, immunogenetic factors of the host may have a role. Recently, a strong ...association between HLA‐DR13 and the self‐limited course of HBV infection has been reported. To determine whether the elimination of HBV is related to a particular HLA allele, we studied the HBV markers and HLA‐DR phenotypes of 1,272 Koreans who had visited Yonsei University Medical Center for renal transplantation. They included 330 renal transplant donors. Subjects were categorized into 3 different groups: the “Unexposed Group” (UE; n = 946) with negative HBV markers, the “Chronic Carrier Group” (CC; n = 83), who were hepatitis B surface antigen (HBsAg)‐positive, and the “Spontaneously Cleared Group” (SC; n = 243), who were HBsAg‐negative with antibodies to HBsAg (anti‐HBs) and hepatitis B core antigen (anti‐HBc). HLA‐DR4 was the most common type in all groups. HLA‐DR6 was significantly more frequent in 69 of 243 subjects with SC (28.4%) than in 8 of 83 subjects with CC (9.6%) (P < .001; relative risk RR = 3.72). HLA‐DR9 was significantly more frequent in CC than in SC (P < .001; RR = 0.33). HLA‐DR13 showed a stronger association with the clearance of HBV than the other HLA‐DR6 subgroup. The distribution of HLA‐DR phenotypes was similar regardless of renal disease. Our data indicate that HLA‐DR6, especially HLA‐DR13, is one of the host factors, which influences the immune response to HBV, and may be associated with self‐elimination of HBV in Koreans.
A single-nucleotide polymorphism (SNP) in the promoter region of MDM2, SNP 309, is associated with hepatocellular carcinoma (HCC) in patients with chronic hepatitis C virus infection. The effect of ...p53 codon 72 polymorphism Arg72Pro on HCC risk remains inconsistent. This study evaluated the association of MDM2 and p53 polymorphisms with the presence and early onset of HCC in Korean patients with chronic hepatitis B virus (HBV) infection. In total, 583 consecutive patients with chronic HBV infection were classified according to the presence (n = 287) or absence (n = 296) of HCC. The MDM2 SNP 309 and p53 Arg72Pro were genotyped using restriction fragment length polymorphism method. The MDM2 G/G and p53 Pro/Pro genotypes were more frequent in HCC group than in non-HCC group (P < 0.001 and P = 0.004, respectively). Multivariate analysis for the presence of HCC revealed that the odds ratio (OR) for MDM2 G/G over T/T was 4.89 (P < 0.001) and that of p53 Pro/Pro over Arg/Arg was 3.03 (P = 0.006). Combined MDM2 G/G and p53 Pro/Pro had a synergistic effect on HCC risk, with an OR of 20.78 (P < 0.001). The mean age of tumor onset in patients with MDM2 G/G genotype was 50.9 years compared with 55.1 with T/T genotype (P = 0.018) and that with p53 Pro/Pro was 49.7 years compared with 52.9 with Arg/Arg (P = 0.040). Thus, MDM2 SNP 309 and p53 Arg72Pro are associated with the early development of HCC in Korean patients with chronic HBV infection.
PDF
