A comparative study of high-dose hepatic arterial infusion chemotherapy and transarterial chemoembolization using doxorubicin for intractable,advanced hepatocellular carcinoma

Background/Aims

Transarterial chemoembolization (TACE) has long been used as a palliative therapy for unresectable hepatocellular carcinoma (HCC). High-dose hepatic arterial infusion chemotherapy (HAIC) has showed favorable outcomes in patients with intractable, advanced HCC. The aim of this study was to compare the effectiveness and safety of high-dose HAIC and conventional TACE using doxorubicin for advanced HCC.

Methods

The high-dose HAIC group comprised 36 patients who were enrolled prospectively from six institutions. The enrollment criteria were good liver function, main portal vein invasion (including vascular shunt), infiltrative type, bilobar involvement, and/or refractory to prior conventional treatment (TACE, radiofrequency ablation, or percutaneous ethanol injection), and documented progressive disease. Patients received 5-fluorouracil (500 mg/m² on days 1~3) and cisplatin (60 mg/m² on day 2 every 4 weeks) via an implantable port system. In the TACE group, 31 patients with characteristics similar to those in the high-dose HAIC group were recruited retrospectively from a single center. Patients underwent a transarterial infusion of doxorubicin every 4~8 weeks.

Results

Overall, 6 patients (8.9%) achieved a partial response and 20 patients (29.8%) had stable disease. The objective response rate (complete response+partial response) was significantly better in the high-dose HAIC group than in the TACE group (16.7% vs. 0%, P=0.030). Overall survival was longer in the high-dose HAIC group than in the TACE group (median survival, 193 vs. 119 days; P=0.026). There were no serious adverse effects in the high-dose HAIC group, while hepatic complications occurred more often in the TACE group.

Conclusions

High-dose HAIC appears to improve the tumor response and survival outcome compared to conventional TACE using doxorubicin in patients with intractable, advanced HCC.     

A new resin matrix for dental composite having low volumetric shrinkage

The applications of dental restorative composite resins containing 2,2 bis [4-(2-hydroxy-3-methacryloyloxy propoxy) phenyl] propane (Bis-GMA), as a base resin, and triethylene glycol dimethacrylate (TEGDMA), as a diluent, are often limited in dentistry due to the relatively large amount of volumetric shrinkage that occurs during the curing reaction. In this study, various new resin matrices were examined for use as dental composites in order to reduce the amount of volumetric shrinkage that occurs in dental composites as a result of curing. Bis-GMA derivatives were synthesized by substituting methyl groups for hydrogen on the phenyl ring. The derivatives of TEGDMA with different chain lengths or reactive groups were also examined. The molecular structural changes in the TEGDMA derivatives were not effective in reducing the level of volumetric shrinkage. The resin matrix containing a Bis-GMA derivative and TEGDMA showed a reduced amount of volumetric shrinkage in proportion to the number of methyl groups on the phenyl rings. Polymerization with a mixture of Bis-GMA, its derivatives and a diluent is a promising strategy for obtaining a polymer with a low amount of volumetric shrinkage. A comparison of the volumetric shrinkage of dental composites containing Bis-GMA, TMBis-GMA (2,2-bis[3,5-dimethyl, 4-(2-hydroxy-3-methacryloyloxy propoxy) phenyl] propane)), and TEGDMA with that prepared from a Bis-GMA and TEGDMA mixture showed that the volumetric shrinkage reduction in the new resin was approximately 50%. Furthermore, the mechanical strength of the former was higher than that of the latter.     

Serum vascular endothelial growth factor and angiopoietin-2 are associated with the severity of systemic inflammation rather than the presence of hemoptysis in patients with inflammatory lung disease

Purpose

Vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2) are major mediators of angiogenesis and are induced by tissue inflammation and hypoxia. The purpose of this study was to investigate whether serum VEGF and Ang-2 are associated with the presence of hemoptysis and the extent of systemic inflammation in patients with inflammatory lung diseases.

Materials and Methods

We prospectively enrolled 52 patients with inflammatory lung disease between June 2008 and October 2009.

Results

The median values of VEGF and Ang-2 were 436 pg/mL and 2383 pg/mL, respectively. There was a significant positive correlation between serum Ang-2 and VEGF levels. VEGF levels were not significantly different according to the presence of hemoptysis. C-reactive protein (CRP) and Ang-2 level were significantly higher in patients without hemoptysis (n=26) than in those with hemoptysis (n=26; p<0.001 and p<0.001, respectively). CRP and arterial oxygen tension (PaO₂) were significantly correlated with both serum VEGF (p=0.032 and p=0.016, respectively) and Ang-2 levels (p<0.001 and p=0.041, respectively), after adjusting for other factors. Age and the absence of hemoptysis were factors correlated with serum Ang-2 levels

Conclusion

Our study suggests that serum VEGF and Ang-2 levels are associated with PaO₂ and the severity of inflammation rather than the presence of hemoptysis in patients with inflammatory lung diseases. Thus, hemoptysis may not be mediated by increased serum levels of VEGF and Ang-2 in patients with inflammatory lung diseases, and further studies are required to determine the mechanisms of hemoptysis.     

The roles of surface chemistry and topography in the strength and rate of osseointegration of titanium implants in bone

The present study investigated the effects of surface chemistry and topography on the strength and rate of osseointegration of titanium implants in bone. Three groups of implants were compared: (1) machine-turned implants (turned implants), (2) machine-turned and aluminum oxide-blasted implants (blasted implants), and (3) implants that were machine-turned, aluminum oxide-blasted, and processed with the micro-arc oxidation method (Mg implants). Three and six weeks after implant insertion in rabbit tibiae, the implant osseointegration strength and rate were evaluated. Surface chemistry revealed characteristic differences of nine at.% Mg for Mg implants and 11 at.% Al for blasted implants. In terms of surface roughness, there was no difference between Mg implants and blasted implants in developed surface ratio (Sdr; p = 0.69) or summit density (Sds; p = 0.96), but Mg implants had a significantly lower arithmetic average height deviation (Sa) value than blasted implants (p = 0.007). At both 3 and 6 weeks, Mg implants demonstrated significantly higher osseointegration strength compared with turned (p = 0.0001, p = 0.0001) and blasted (p = 0.0001, p = 0.035) implants, whereas blasted implants showed significantly higher osseointegration than turned implants at 6 weeks (p = 0.02) but not at 3 weeks (p = 0.199). The present results not only support the hypothesis that biochemical bonding facilitates rapid and strong integration of implants in bone, but also provide evidence for biochemical bonding theory previously proposed by Sul.     

Xenophagy in Helicobacter pylori‐ and Epstein–Barr virus‐induced gastric cancer

Helicobacter pylori and Epstein–Barr virus (EBV) account for roughly 80% and 10%, respectively, of gastric carcinomas worldwide. Autophagy is an evolutionarily conserved and intricately regulated cellular process that involves the sequestration of cytoplasmic proteins and organelles into double‐membrane autophagosomes that eventually fuse with lysosomes for degradation of the engulfed content. Emerging evidence indicates that xenophagy, a form of selective autophagy, plays a crucial role in the pathogenesis of H. pylori‐ and EBV‐induced gastric cancer. Xenophagy specifically recognizes intracellular H. pylori and EBV and physically targets these pathogens to the autophagosomal–lysosomal pathway for degradation. In this connection, H. pylori or EBV‐induced dysregulation of autophagy may be causally linked to gastric tumourigenesis and therefore can be exploited as therapeutic targets. This review will discuss how H. pylori and EBV infection activate autophagy and how these pathogens evade recognition and degradation by the autophagic pathway. Elucidating the molecular aspects of H. pylori‐ and EBV‐induced autophagy will help us better understand the pathogenesis of gastric cancer and promote the development of autophagy modulators as antimicrobial agents. Published by John Wiley & Sons, Ltd     

Clinical outcomes of transjugular intrahepatic portosystemic shunt for portal hypertension: Korean multicenter real-practice data

Background/Aims

This retrospective study assessed the clinical outcome of a transjugular intrahepatic portosystemic shunt (TIPS) procedure for managing portal hypertension in Koreans with liver cirrhosis.

Methods

Between January 2003 and July 2013, 230 patients received a TIPS in 13 university-based hospitals.

Results

Of the 229 (99.6%) patients who successfully underwent TIPS placement, 142 received a TIPS for variceal bleeding, 84 for refractory ascites, and 3 for other indications. The follow-up period was 24.9±30.2 months (mean±SD), 74.7% of the stents were covered, and the primary patency rate at the 1-year follow-up was 78.7%. Hemorrhage occurred in 30 (21.1%) patients during follow-up; of these, 28 (93.3%) cases of rebleeding were associated with stent dysfunction. Fifty-four (23.6%) patients developed new hepatic encephalopathy, and most of these patients were successfully managed conservatively. The cumulative survival rates at 1, 6, 12, and 24 months were 87.5%, 75.0%, 66.8%, and 57.5%, respectively. A high Model for End-Stage Liver Disease (MELD) score was significantly associated with the risk of death within the first month after receiving a TIPS (P=0.018). Old age (P<0.001), indication for a TIPS (ascites vs. bleeding, P=0.005), low serum albumin (P<0.001), and high MELD score (P=0.006) were associated with overall mortality.

Conclusions

A high MELD score was found to be significantly associated with early and overall mortality rate in TIPS patients. Determining the appropriate indication is warranted to improve survival in these patients.     

Physical development in children and adolescents with bronchial asthma

Bronchial asthma is the most common chronic disease in children of developmental age. Data from the auxological literature indicate that children with disturbances in growth may also suffer from atopic disorders. The aim of the present study was to evaluate somatic growth in children with bronchial asthma using anthropological methods. The study was carried out using anthropometric measurements and information on the severity and course of the disease on 261 children with bronchial asthma. Mean body height was lower than in healthy peers and about 5% of subjects were short. Mean BMI and skinfold thicknesses were significantly higher and lean body mass was lower in the study group. Seventeen percent of the children were overweight or obese, and 8% were underweight. Body build was more robust in the girls examined. Longitudinal studies will help determine to what degree the disease itself directly affects physical development, and to what degree treatment does.