Decrease in size of non-treated lesions after cryoablation for hepatocellular carcinoma

We present the case of one 58-year-old man with advancd hepatocellular carcinoma and hepatitis-B virus-related liver cirrhosis who received hepatic cryoablation. Magnetic resonance imaging (MRI) showed multiple liver tumors and the diameter of the largest tumor was more than 10cm. The patient received 2 percutaneous cryoablations in December 2009 and January 2010. Ten months later, MRI showed that not only the treated areas underwent necrosis but also the non-treated area decreased. The a-fetoprotein (AFP) level and the frequency of circulated regulatory T cell (Treg) before treatment were 13,800ng/mL and 15.6%, respectively. Following the cryoablations they dropped to 436ng/mL and 7.6%, respectively, 10 months later. The patient remains in good condition until now.     

Monitoring of Intrasplenic Hepatocyte Transplantation for Acute-on-Chronic Liver Failure: A Prospective Five-Year Follow-Up Study

Background

Acute-on-chronic liver failure (ACLF) is defined as an acute deterioration of chronic liver disease. Intrasplenic hepatocyte transplantation is increasingly recognized as a treatment for liver failure and genetic metabolic liver diseases. We describe our experience of intrasplenic hepatocyte transplantation in a small cohort of patients as bridge therapy or as an alternative to orthotopic liver transplantation (OLT).

Methods

Seven patients with ACLF with an expected survival of less than 8 weeks were enrolled into the study. The donor hepatocytes were collected from 2 healthy males and cryopreserved. Donor hepatocytes were transplanted into the spleen of recipients via catheterization of the femoral artery. All patients were followed up for 5 years or to death.

Results

A total of (4.2–6.0) × 10¹⁰ hepatocytes were harvested from the 2 donors' livers and their survival after recovery from the frozen stock was 63% ± 2.8% and 73.5% ± 3.2%, respectively. Following intrasplenic hepatocyte transplantation, 3 patients fully recovered from liver failure, 1 survived and subsequently underwent OLT, and the remaining 3 patients died between 2.5 and 12 months after intrasplenic hepatocyte transplantation. At month 48 post–intrasplenic hepatocyte transplantation, living hepatocyte signals were observed in the spleen using magnetic resonance imaging (MRI) with gadobenate dimeglumine (Gd-BOPTA).

Conclusions

Intrasplenic hepatocyte transplantation is a promising therapy for liver failure that may reduce mortality rates among patients with end-stage liver disease awaiting OLT. Conceivably, intrasplenic hepatocyte transplantation may be considered an alternative to OLT for patients with acute liver failure. MRI (Gd-BOPTA) is a useful tool for detecting living hepatocytes in the spleen after intrasplenic hepatocyte transplantation.     

氩氦冷冻消融治疗进展期肝癌的疗效及其影响因素研究

目的探讨氩氦冷冻消融治疗乙型肝炎相关性进展期肝细胞癌(HCC)的临床疗效和影响生存期的因素。方法采用临床列队对照研究190例乙型肝炎相关性进展期HCC患者,其中147例行氩氦冷冻消融治疗,43例未行局部消融和肝动脉化疗栓塞治疗。结果氩氦冷冻消融乙型肝炎相关性进展期HCC患者生存期为10.11个月,未治疗者生存期仅为4.73个月,氩氦冷冻消融治疗进展期HCC严重肝损伤发生率为5.4%,Child-Pugh分级≥B8的病例占87.5%,胆红素水平51.3μmol/L者占75%;在HBV相关性进展期HCC中,HBV DNA载量中、低水平占91%,HBeAg阴性患者占66.67%,两者与肿瘤细胞分化程度无关;肝硬化程度及肿瘤细胞分化程度是影响进展期HCC患者生存期的关键因素。结论冷冻消融治疗乙型肝炎相关性进展期HCC能显著延长患者的生存期,是影响进展期HCC生存期的独立因素;Child-Pugh分级≥B8,伴有胆红素水平51.3μmol/L的进展期HCC患者不适宜行冷冻消融;肝硬化程度及肿瘤细胞分化程度是影响进展期HCC患者生存期的关键因素。     

Increased expression of phospho-acetyl-CoA carboxylase protein is an independent prognostic factor for human gastric cancer without lymph node metastasis

Triptolide is a traditional Chinese medicinal herb-derived antineoplastic agent. However, its antitumor activity against gynecologic carcinomas has not yet been well described. It is the purpose of this article to investigate the effect and mechanism of triptolide in human ovarian cancer using both A2780 (p53 wild) and OVCAR-3 (p53 mutated) cells. Our results showed that triptolide exerted a potent inhibitory effect on the growth and proliferation of both cell lines in a dose- and time-dependent manner and that the effect was independent of the expression of p53. In contrast, triptolide had only a marginal cytotoxicity in noncancerous ovary cells, lung fibroblast cells, and macrophage cells, indicating differential inhibitory effects of the drug on cell growth between ovarian cancer cells and normal tissue cells. Exposure of the ovarian cancer cells to triptolide induced apoptosis, as evaluated by annexin V/propidium iodide-labeled flow cytometry. Triptolide-induced apoptosis was accompanied by cytochrome c release and caspase-3 activation and was associated with downregulation of Bcl-2 and upregulation of Bax. Cell cycle analysis demonstrated that treatment with triptolide induced cell cycle S phase arrest in A2780 cells and G2/M phase arrest in OVCAR-3 cells. Further detection by Western blotting revealed that the cell cycle arrest by triptolide in both cell lines occurred in concert with increased expression of p21^CIP1/WAF1. This study shows that triptolide selectively kills ovarian cancer cells with different p53 status predominantly through regulating the coordinate and dynamic cellular processes of proliferation and apoptosis, thereby making it a promising chemotherapeutic agent against a broad spectrum of ovarian carcinomas.     

中医药阻断逆转肝纤维化的现状、希望与挑战

中医药辨证论治具有阻断逆转肝纤维化的整体治疗优势,是未来治疗肝纤维化候选药物的源泉。概述了中医药治疗肝纤维化的渊源和现状,重点论述了如何按照循证医学和国际认同的临床试验标准再评价中医药阻断逆转肝纤维化的临床疗效和安全性,介绍了最新临床研究成果。强调了发掘和认同中医药阻断逆转肝纤维化所面临的挑战与重要意义。     

Human intrahepatic biliary epithelial cells engulf blebs from their apoptotic peers

The phagocytic clearance of apoptotic cells is critical for tissue homeostasis; a number of non‐professional phagocytic cells, including epithelial cells, can both take up and process apoptotic bodies, including the release of anti‐inflammatory mediators. These observations are particularly important in the case of human intrahepatic biliary cells (HiBEC), because such cells are themselves a target of destruction in primary biliary cirrhosis, the human autoimmune disease. To address the apoptotic ability of HiBECs, we have focused on their ability to phagocytize apoptotic blebs from autologous HiBECs. In this study we report that HiBEC cells demonstrate phagocytic function from autologous HiBEC peers accompanied by up‐regulation of the chemokines CCL2 [monocyte chemotactic protein‐1 (MCP‐1)] and CXCL8 [interleukin (IL)‐8]. In particular, HiBEC cells express the phagocytosis‐related receptor phosphatidylserine receptors (PSR), implying that HiBECs function through the ‘eat‐me’ signal phosphatidylserine expressed by apoptotic cells. Indeed, although HiBEC cells acquire antigen‐presenting cell (APC) function, they do not change the expression of classic APC function surface markers after engulfment of blebs, both with and without the presence of Toll‐like receptor (TLR) stimulation. These results are important not only for understanding of the normal physiological function of HiBECs, but also explain the inflammatory potential and reduced clearance of HiBEC cells following the inflammatory cascade in primary biliary cirrhosis.     

氩氦刀冷冻消融治疗乙型肝炎病毒相关性肝细胞癌前后PD-1的变化及其与预后的关系

目的 观察氩氦冷冻消融治疗对乙型肝炎病毒相关性肝细胞癌(HCC)患者外周血细胞程序性死亡受体-1(PD-1)表达的影响,分析PD-1与HCC病程及患者预后的关系.方法 收集2006年1月-2009年1月收治的乙型肝炎病毒相关性HCC患者141例,其中男109例,女32例,年龄28～71岁,巴塞罗那分期(BCLC)早期4...     

肝癌干细胞与肝癌细胞表面分子标记物的鉴别

目的探讨肝癌干细胞与普通肝癌细胞表面分子标记物的差别。方法采用免疫组织化学方法在HepG2、Hep-11、Hep-12细胞株中对CD34、CD56、CD117、CD133、Nanog、OCT4的表达进行观察。结果 CD34、CD117、CD133在Hep-12细胞中表达的阳性率最高,在Hep-11中表达的阳性率下降或为阴性,而在HepG2细胞中均为阴性;CD56在Hep-12及Hep-11细胞中表达强度相当,在HepG2中为阴性;Nanog及OCT4在3种细胞株中均表达阴性。结论 CD34、CD117、CD133可能在鉴别肝癌干细胞与肝癌细胞的表面分子标记物方面具有重要意义。     

Cryoablation Versus Radiofrequency Ablation for Hepatic Malignancies: A Systematic Review and Literature-Based Analysis

The aim of this study is to summarize and quantify the current evidence on the therapeutic efficacy of cryoablation compared with radiofrequency ablation (RFA) in patients with hepatic malignancies in a meta-analysis.Data were collected by searching PubMed, Scopus, and Cochrane databases for reports published up to May 26, 2015. Studies that reported data on comparisons of therapeutic efficacy of cryoablation and RFA were included. The random effects model was used to estimate the pooled relative risks of events comparing cryoablation to RFA for therapy of hepatic malignancies.Seven articles met the inclusion criteria and were included in the meta-analysis. The meta-analysis showed that there was no statistically significant difference in mortality of at least 6 months (odds ratio [OR] = 1.00, 95% confidence interval [CI]: 0.68–1.49) and local tumor progression according to both patients (OR = 1.64, 95% CI: 0.57–4.74) and tumors (OR = 1.81, 95% CI: 0.74–4.38) between cryoablation group and RFA group. However, the risk of complications was significantly higher in the cryoablation group than that in the RFA group (OR = 2.93, 95% CI: 1.15–7.46). When considering the specific complications, only thrombocytopenia (OR = 51.13, 95% CI: 2.92–894.21) and renal impairment (OR = 4.19, 95% CI: 1.34–13.11) but not other complications were significantly higher in the cryoablation group.In conclusion, the 2 methods had almost equal mortality and nonsignificant difference in local tumor progression, with higher risk of complications in cryoablation. Further large-scale, well-designed randomized controlled trials are needed to identify the current findings and investigate the long-term effects of cryoablation compared with RFA for therapy of hepatic malignancies.     

Outcomes of ultrasound-guided percutaneous argon-helium cryoablation of hepatocellular carcinoma

Purpose

To evaluate the efficacy and safety of ultrasound (US)-guided percutaneous argon-helium cryoablation for hepatocellular carcinoma (HCC) and determine appropriate indications.

Methods

We reviewed outcomes of 300 HCC patients who underwent US-guided percutaneous cryoablation.

Results

Overall, 223 tumors (mean diameter 7.2?±?2.8?cm) in 165 patients were incompletely ablated, while 185 tumors (mean diameter 5.6?±?0.8?cm, P?=?0.0001 vs. incomplete ablation) in 135 patients were completely ablated. Nineteen patients (6.3%) developed serious complications while in hospital, including cryoshock syndrome in six patients, hepatic bleeding in five, stress-induced gastric bleeding in four, liver abscess in one and intestinal fistulas in one. Two patients died because of liver failure. The median follow-up was 36.7?months (range 6–63?months). The local tumor recurrence rate was 31%, and was related to tumor size (P?=?0.029) and tumor location (P?=?0.037). The mean survival duration of patients with early, intermediate and advanced HCC (Barcelona Clinic Liver Cancer staging system) was 45.7?±?3.8, 28.4?±?1.2 and 17.7?±?0.6?months, respectively.

Conclusions

US-guided percutaneous cryoablation is a relatively safe and effective therapy for selected HCC patients.