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.     

Effect of drug-loaded TiO<Subscript>2</Subscript> nanotube arrays on osseointegration in an orthodontic miniscrew: an <Emphasis Type="Italic">in-vivo</Emphasis> pilot study

Osseointegration was evaluated for the surface of miniscrews with TiO₂ nanotube arrays containing drugs in this in-vivo study. The diameter and length of the TiO₂ nanotube arrays were about 70 nm and 5 μm, respectively. Recombinant human bone morphogenetic protein-2 (rhBMP-2) or ibuprofen was loaded in the TiO₂ nanotube arrays with 12 miniscrews. The 12 drug-loaded miniscrews, 6 miniscrews with no drug-loaded TiO₂ nanotube arrays and 6 conventional miniscrews, were placed on the tibias of New Zealand white rabbits. Histological osseointegration was assessed 8 weeks after implantation by measuring the bone-to-implant contact (BIC) ratio. Ibuprofen-loaded miniscrews showed a significantly higher BIC of 71.6% over conventional miniscrews of 44.3% on average. The mean BIC ratios of rhBMP-2-loaded miniscrews and no drug-loaded miniscrews was 24.6% and 60.1%, respectively. Our results suggest that TiO₂ nanotube arrays on the surface of miniscrews could be used as carriers of drugs, and loading ibuprofen in TiO₂ nanotube arrays may improve osseointegration of miniscrews. However, the effect of rhBMP-2 loaded in TiO₂ nanotube arrays on osseointegration of miniscrews was questionable in this pilot study.     

The Effect of Denosumab and Risk Factors for Recurrence in Spinal Giant Cell Tumors: A Systematic Review and Meta-Analysis

PurposeGiant cell tumors (GCTs) are common benign primary bone tumors and are well known for their locally aggressive performance and tendency to recur. The purpose of this study was to analyze the effects of denosumab and risk factors for recurrent spinal GCTs.Materials and MethodsWe searched PubMed, EMBASE, Web of Science, and Cochrane Library databases to identify differences between individuals treated with and without denosumab and risk factors for spinal GCT recurrence. Patient data, including age, sex, tumor resection range, location, denosumab use, Campanacci grade, and radiotherapy, were documented. Comparable factors were evaluated using odds ratios (ORs) and weighted mean differences (WMDs) with 95% confidence intervals (CIs).ResultsSixteen studies were included. The overall incidence of spinal GCT recurrence was 29%. Campanacci grade III tumors showed better recurrence outcomes than grades I and II (OR, 16.36; 95% CI, 4.19–63.93; p<0.001). Gross total resection (OR, 0.09; 95% CI, 0.04–0.19; p<0.001), radiotherapy (OR, 0.27; 95% CI, 0.11–0.65; p=0.004), and the use of denosumab during subtotal resection (OR, 2.95; 95% CI, 1.07–8.17; p=0.04) were important factors for reducing recurrence.ConclusionClinicians must consider the effects of gross total resection, radiotherapy use, and denosumab use in cases of subtotal resection during spinal GCT treatment. So far, many researchers have used denosumab in spinal GCT, but none have clearly suggested an endpoint. Most studies, however, recommend using it for more than 6 months.     

Alcohol-associated capillarization of sinusoids: A critique since the discovery by Schaffner and Popper in 1963

This article reviews the literature on capillarization of hepatic sinusoids since its discovery in 1963. Liver sinusoidal endothelial cells are uniquely fenestrated and lack an underlying basement membrane. In chronic liver disease, the sinusoids capillarize and transform into systemic capillaries, a process termed capillarization of sinusoids. The histopathology is marked by defenestration, basement membrane formation, and space of Disse fibrogenesis. Capillarized sinusoids compromise the bidirectional exchange of materials between sinusoids and hepatocytes, leading to hepatocellular dysfunction. Sinusoidal capillarization was first described in active cirrhosis of alcoholics in 1963. Since then, it has been found in early and progressive stages of alcoholic hepatic fibrosis before the onset of cirrhosis. The sinusoidal structure is not altered in alcoholic steatosis without fibrosis. Defenestration impairs the ability of the endothelium to filter chylomicron remnants from sinusoids into the Disse's space, contributing to alcohol-induced postprandial hyperlipidemia and possibly atherosclerosis. Ethanol also modulates the fenestration dynamics in animals. In baboons, chronic alcohol consumption diminishes endothelial porosity in concomitance with hepatic fibrogenesis and in rats defenestrates the endothelium in the absence of fibrosis, and sometimes capillarizes the sinusoids. Acute ethanol ingestion enlarges fenestrations in rats and contracts fenestrations in rabbits. In sinusoidal endothelial cell culture, ethanol elicits fenestration dilation, which is likely related to its interaction with fenestration-associated cytoskeleton. Ethanol potentiates sinusoidal injury caused by cocaine, acetaminophen or lipopolysaccharide in mice and rats. Understanding ethanol's mechanisms on pathogenesis of sinusoidal capillarization and fenestration dynamics will lead to development of methods to prevent risks for atherosclerosis in alcoholism.     

A Case Report of Testicular Sparganosis Misdiagnosed as Testicular Tumor

Sparganosis is a parasitic infestation of human by plerocercoid larvae. Sparganum is usually reported to be found in the subcutaneous tissues as well as other organs, including scrotum. However, testicular sparganosis is extremely rare, because of strong capsule of tunica albuginea. An urban-living 54-yr-old Korean man presented with left scrotal pain for 6 yr. Both testes look normal physically. Ultrasonography revealed poorly defined, heterogeneous mass with increased echogenicity in the left testis. This case was misdiagnosed as testicular tumor and underwent orchiectomy, but was diagnosed as testicular sparganosis by histopathology. Sparganosis should be included for differential diagnosis of testis tumor in countries where sparganosis is prevalent.

Graphical Abstract

相似文献   

Classification system for flexor digitorum accessorius longus muscle variants within the leg: Clinical correlations

The flexor digitorum accessorius longus (FDAL), a variant leg muscle, can cause tarsal tunnel syndrome. This study was performed to classify the variants of the FDAL by dissection and to correlate the dissection results with clinical cases of tarsal tunnel syndrome caused by this muscle. Eighty lower limbs of embalmed Korean cadavers were dissected. MR images of two clinical cases of tarsal tunnel syndrome caused by the FDAL were correlated with the dissection results. The FDAL was observed in nine out of 80 specimens (11.3%) and it was classified into three types depending on its site of origin and its relationship to the posterior tibial neurovascular bundle (PTNV) in the leg. In Type I (6.3%), the FDAL originated in the leg and ran superficially along the PTNV, either not crossing (Type Ia, 3.8%) or crossing (Type Ib, 2.5%) the neurovascular bundle. In Type II (6.3%), it originated in the tarsal tunnel. Most FDALs followed a similar course in the tarsal tunnel and the plantar pedis. On correlating the MR images of the clinical cases with this classification, the FDAL corresponded to Types Ia and II. All three types of FDAL can compress the tibial nerve in the tarsal tunnel or the distal leg. Clarification of the topographical relationship between this muscle and the PTNV would help to improve the results of surgery for tarsal tunnel syndrome caused by the FDAL. Clin. Anat. 27:1111–1116, 2014. © 2014 Wiley Periodicals, Inc.     

Molecular mechanism for loss of visual cortical responsiveness following brief monocular deprivation

A dramatic form of experience-dependent synaptic plasticity is revealed in visual cortex when one eye is temporarily deprived of vision during early postnatal life. Monocular deprivation (MD) alters synaptic transmission such that cortical neurons cease to respond to stimulation of the deprived eye, but how this occurs is poorly understood. Here we show in rat visual cortex that brief MD sets in motion the same molecular and functional changes as the experimental model of homosynaptic long-term depression (LTD), and that prior synaptic depression by MD occludes subsequent induction of LTD. The mechanisms of LTD, about which there is now a detailed understanding, therefore contribute to visual cortical plasticity.     

Differential expression of hypoxia inducible factor-1 alpha and tumor cell proliferation between squamous cell carcinomas and adenocarcinomas among operable non-small cell lung carcinomas

This study aimed to evaluate whether the elevated level of hypoxia-inducible factor-1alpha (HIF-1alpha) correlated with histologic types, angiogenesis, tumor cell proliferation, and clinical parameters in common non-small cell lung carcinomas (NSCLCs). We performed immunohistochemical stains using paraffin-embedded tissue blocks from 84 cases of operable NSCLC [No. of squamous cell carcinoma (SCC), 45; No. of adenocarcinoma (AC), 39]. HIF-1alpha expression was related with histologic types (66.7% in SCCs vs 20.5% in ACs, p<0.001), but not with lymph node status, tumor stage, vascular endothelial growth factor expression, microvessel density (MVD), and proliferating cell nuclear antigen (PCNA) index (p>0.05, respectively). As for the histologic types, MVD and PCNA index were significantly higher in SCCs than in ACs (p=0.009 and p=0.016, respectively). Among HIF-1alpha positive carcinomas, MVD was significantly higher in HIF-1alpha positive SCCs than in HIF-1alpha positive ACs (p=0.023). The overall survival curves were not associated with HIF-1alpha expression or any other histologic parameters (p>0.05). These findings suggest that HIF-1alpha expression in NSCLCs may play a differential role according to histologic types, but its prognostic significance is indeterminate.