肝动脉化疗栓塞对原发性肝癌患者HBV DNA水平的影响

背景与目的：化疗可抑制恶性肿瘤患者的免疫功能,导致合并乙型肝炎病毒（hepatitis B virus,HBV）感染的肿瘤患者出现HBV激活,严重影响了患者的预后。本研究旨存了解肝癌患者肝动脉化疗栓塞（trans catheter arterial ehemoembolization,TACE）前后乙型肝炎病毒脱氧核糖核酸（HBVDNA）含量的变化及其影响凶素。方法：回顾性分析2004年12月至2008年7月期间,162例肝癌患者TACE治疗前后HBVDNA的变化．并分析HBVDNA变化与AFP的关系。结果：治疗后HBVDNA阳性率较治疗前显著降低『55．6％VS．71．6％,P〈0．01]。治疗前HBVDNA≥ 1×10^5／L者更易出现HBVDNA水平的下降（OR=2．7,P〈0．01）;治疗后AFP的下降与HBVDNA下降有关联（OR=2．6,P〈O．05）。结论：TACE能降低HBV相关的肝癌患者体内的HBVDNA水平,特别是治疗前HBVDNA≥ 1×10^5／L者及治疗后AFP降低者。     

肝癌患者术后肝动脉化疗栓塞联合胸腺肽治疗预防复发的随机对照研究

目的 随机对照观察肝癌患者术后肝动脉化疗栓塞(TACE)联合胸腺肽α1(Tα1)治疗对预防肝细胞癌复发的影响。方法 57例肝细胞癌患若随机分为3组：手术＋TACE Tα1组(A组)18例,手术＋FACE组(B组)23例和手术切除组(C组)16例。观察患者术后肿瘤复发率、复发时间和生存期。结果 A、B、C组1年复发率分别为83．3％、87．0％和87．5％(P=0．926),中位复发时间分别为7．0个月、5．0个月和4,0个月(P=0,039),中位生存期分别为10．0个月、7．0个月和8,0个月(P=0．002)。结论 术后TAC：E rr0．治疗不能降低肝细胞癌患者术后复发率,但可延缓复发时间,提高生存期。     

经肝动脉栓塞化疗对细胞免疫状态影响

经导管肝动脉化疗栓塞(TACE)作为肝细胞肝癌(HCC)姑息治疗，可明显提高HCC患者的生存期．疗效肯定，但远期效果并不理想，因此人们逐渐认识到该方法在起到治疗作用的同时也给机体的免疫功能造成一定的影响。本文在复习国内、外有关文献基础上．对HCC患者TACE前后的T细胞亚群等进行检测和观察。     

肝癌患者肝动脉化疗栓塞术后血液指标对栓塞综合征预测价值分析

目的观察肝细胞肝癌患者肝动脉化疗栓塞术(transarterial chemoembolization,TACE)后血液指标的改变与栓塞综合征的发生关系,分析血液指标变化的临床意义。方法回顾性分析2011-10-01-2013-09-30中国医科大学附属第一医院接受治疗的283例TACE术后肝细胞肝癌患者的病例资料,采用单因素以及多因素分析法对患者术中应用碘油的剂量、术前及术后第1次血液检测指标的结果与栓塞综合征的发生情况进行分析。采用结构方程模型分析影响栓塞综合征发生因素之间的关系。使用ROC曲线评估血液指标对判别栓塞综合征的预测性能。结果肝细胞肝癌患者TACE后发生栓塞综合征240例,发生率84.81%(240/283)。发生栓塞综合征的患者应用碘油的剂量(z=-3.675,P<0.001)、术后白细胞(z=-2.570,P=0.010)、术后中性粒细胞百分比(z=-3.867,P<0.001)、丙氨酸氨基转移酶(alanine transaminase,ALT)(z=-2.051,P=0.040)显著高于未发生栓塞综合征的患者;术后血清白蛋白(z=-3.342,P=0.001)、总胆红素(z=-1.992,P=0.046)、血清Na+的指标(t=-2.842,P=0.005)显著低于未发生栓塞综合征患者。中性粒细胞百分比是栓塞综合征发生的危险因素(OR=1.025,95%CI为1.006~1.044,P=0.009),血清白蛋白是栓塞综合征发生的保护因素(OR=0.979,95%CI为0.961~0.998,P=0.030)。碘油既可以通过直接作用导致患者栓塞综合征的发生,亦可通过中性粒细胞百分比、血清白蛋白、ALT和血清Na+等血液变化成为栓塞综合征发生的一个间接作用因素。肝癌患者TACE后中性粒细胞百分比、血清白蛋白和ALT对栓塞综合征的发生有预测作用(ROC曲线下的面积分别为0.651、0.673和0.596)。结论肝细胞肝癌患者TACE后中性粒细胞百分比、血清白蛋白、ALT、血清Na+对患者术后栓塞综合征的发生有较好的预测价值,可作为栓塞综合征发生的评估和预测指标,有助于肝癌患者介入术后护理计划的实施。     

原发性肝癌肝动脉化疗栓塞术的护理

原发性肝癌肝动脉化疗栓塞术的护理王裕珍自１９９０年４月～１９９４年４月，我们采用Ｓｅｌｄｉｎｇｅｒ氏法，对２６例不能手术切除的原发性肝癌患者行肝动脉化疗栓塞术（ＨＡＩ＋ＨＡＥ），共３１人次，现将护理体会总结如下。资料和方法一、临床资料２６例患者均经Ｂ...     

肝动脉栓塞化疗治疗中晚期肝癌的临床研究

目的：研究肝动脉拴塞化疗治疗中晚期肝癌的疗效。方法：对118例经肝动脉栓塞化疗治疗的中晚期肝癌患者评价疗效并随访2a以上，观察其生存率。结果：完全缓解8例，部分缓解49例。轻微缓解44例，无变化17例。有效率达85．6％。1a生存率为66．9％，2a生存率为31．4％。结论：肝动脉栓塞化疗治疗中晚期肝癌疗效确切，副作用较少，易于在基层医院推广。     

肝动脉化疗栓塞治疗中晚期肝癌的临床分析

目的：通过中晚期肝癌患者的肝动脉化疗栓塞（TACE）的临床观察,探讨该方法的应用价值。方法：采用seldinger技术,经皮股动脉插管进行肝动脉灌注化疗药物加栓塞剂。结果：通过对241例患者随访,治疗后4-6周复查CT、B超肿块有不同程度缩小,AFP降低至原来数值的50%以下占68%。本组患者治疗后1、2、3年生存期分别为65.3%、27.2%、10.1%。平均生存期为17.6个月。结论：肝动脉化疗栓塞（TACE）治疗中晚期肝癌是一种有效方法,虽属姑息治疗,但可减轻症状,延长生命。     

残癌危险因素对肝癌切除术后肝动脉栓塞化疗效果的影响

目的 探讨术后辅助性肝动脉栓塞化疗对残癌低危和残癌高危患者预后的不同影响。方法 进入研究的病例分为干预组(辅助性动脉栓塞化疗组)和对照组(未行辅助性动脉栓塞化疗),根据残癌的高危因素将肝癌切除术的患者分为残癌高危者和残癌低危者,采用病例对照实验设计,以单因素统计方法和Cox模型,分析研究术后辅助性肝动脉栓塞化疗对肝癌切除术患者预后的影响,以及残癌高危因素对辅助性动脉栓塞化疗作用的影响。结果 对于残癌低危患者,干预组和对照组术后1,2,3,4年生存率分别为97．2％、78．0％、66．5％、66．5％和91．2％、81．4％、70．3％、54．4％,生存率差异无显著性(P=0．7667);而对于残癌高危患者,干预组和对照组术后1,2,3,4年生存率分别为89．5％、73．4％、59．2％、53．8％和70．5％、61．9％、46．8％、46．8％,生存率差异有显著性(P=0．0029)。Cox比例风险模型分析结果显示,辅助性动脉栓塞化疗对切除术后肝癌患者预后的影响,决定于患者有无残癌的危险因素,辅助性动脉栓塞化疗不是影响患者预后的独立因素。结论 术后给予辅助性肝动脉栓塞化疗,可延长有残癌高危因素患者的生存期,而对于无残癌危险因素的患者,术后辅助性肝动脉栓塞化疗不能延长生存期。     

原发性肝癌肝动脉栓塞化疗预后影响因素的分析

原发性肝癌 (ｈｅｐａｔｏｃｅｌｌｕｌａｒｃａｒｃｉｎｏｍａ ,ＨＣＣ)肝动脉化疗栓塞 (ｔｒａｎｓｃａｔｈｅｔｅｒａｒｔｅｒｉａｌｃｈｅｍｏｅｍｂｏｌｉｚａｔｉｏｎ ,ＴＡＣＥ)疗效肯定[1～ 4 ] ,但影响患者预后的因素很多[5～ 6 ] 。作者收集我院 1990年 1月～ 2 0 0     

肝、脾动脉双途径化疗栓塞治疗中晚期肝癌

肝动脉化疗栓塞（ＨＡＩ＋ＨＡＥ）是目前公认的治疗失去手术机会的中晚期肝癌的首选方法,单独 ＨＡＩ＋ＨＡＥ治疗往往力度不够,选择在此基础上的综合疗法一直是临床治疗的热点。我们经肝、脾动脉双途径化疗栓塞治疗中晚期肝癌３０例,报告如下。 １ 材料与方法１．１ 临床资料 经ＡＦＰ、肝组织活检病理及Ｂ超、ＣＴ证实的原发性肝癌３０例;男２３例,女７例;年龄３２～７４岁。肿瘤直径：＜ ５ｃｍ ４例,６～１０ｃｍ ２０例,＞１０ｃｍ ６例;结节型１８例,弥漫型１２例。伴有门静脉分支癌栓９例。预计生存期超过 ３个月。 所有…     

肝细胞癌患者术前ＨＢＶ ＤＮＡ含量对术后肝功能影响的初步研究

目的　探讨肝细胞癌（ＨＣＣ）患者术前ＨＢＶＤＮＡ含量对切除术后肝功能恢复的影响。方法　收集我科２００７年１月至２００７年６月行手术切除治疗的原发性肝癌患者共２１７例,应用实时荧光定量ＰＣＲ方法检测血清中ＨＢＶＤＮＡ,按照ＨＢＶＤＮＡ含量分为两组：Ａ组（ＨＢＶＤＮＡ≥１.０×１０^５拷贝／ｍｌ）６８例,Ｂ组（ＨＢＶＤＮＡ＜１.０×１０^５拷贝／ｍｌ）１４９例。严密观察患者术后肝功能变化情况,采用ＳＰＳＳ１３.０软件进行统计分析。结果　术后两组患者的肝功能变化存在着显著差异,Ａ组的肝功能损伤程度高于Ｂ组。术后第１、３、７天,丙氨酸氨基转移酶（ＡＬＴ）和天门冬氨酸氨基转移酶（ＡＳＴ）数值Ａ组明显高于Ｂ组,而前白蛋白数值则Ｂ组高于Ａ组,两组差异有统计学意义（Ｐ＜００５）;术后第３、７天,总胆红素（ＴＢＩＬ）数值Ａ组明显高于Ｂ组,两组差异有统计学意义（Ｐ＜０.０５）。除术前凝血酶原时间（ＰＴ）、前白蛋白、ＴＢＩＬ、ＡＳＴ和术中肝门阻断时间外,术前ＨＢＶＤＮＡ浓度对术后第７天的血清ＴＢＩＬ水平有显著影响。结论　ＨＣＣ患者术前ＨＢＶＤＮＡ含量对于术后肝功能恢复有明显影响,对术前ＨＢＶＤＮＡ含量较高的患者应在治疗肝癌的同时给予抗病毒治疗。     

Relation of changes in hepatitis B virus replication markers to the outcome of interferon treatment in patients with chronic hepatitis.

The relationship between the behavior of hepatitis B virus (HBV) replication markers and the response to treatment with recombinant alpha-2b interferon (IFN) was investigated in 11 patients with chronic hepatitis. At the end of 6 months of treatment, 4 patients showed a complete response to IFN: 2 more patients had seroconversion to HBeAb after 8 and 9 months of follow-up, respectively. The response to IFN was partial in the remaining patients. Pre-treatment levels of HBV DNA in patients showing complete response were lower than pre-treatment levels in patients with partial response: in addition, serum HBV DNA clearance during the treatment was associated with sustained remission more frequently than changes in the HBeAg/HBeAb system.     

The effect of prophylactic lamivudine on hepatitis B virus reactivation in HBsAg-positive patients with diffuse large B-cell lymphoma undergoing prolonged rituximab therapy

The association of prolonged rituximab therapy and hepatitis B virus (HBV) reactivation in diffuse large B-cell lymphoma (DLBCL) and the role of lamivudine prophylaxis remain undefined. The prevalence and mortality of HBV reactivation in HBsAg-positive patients with DLBCL undergoing rituximab-based treatment, who received prophylactic treatment with or without lamivudine, were retrospectively analyzed. From January 2003 to December 2009, there were 50 patients enrolled in the study, among of which 30 received the prophylactic treatment of lamivudine and 20 without prophylactic treatment of lamivudine. Among of the 50 patients, seven patients received further rituximab maintenance, once every 3 months for 2 years. Compared with lamivudine treatment group, it showed that there was significantly higher prevalence of HBV reactivation (60.0% vs 13.3%, P = .001), severe hepatitis (45.0% vs 6.7%, P = .004), and mortality (25.0% vs 3.3%, P = .032) in non-lamivudine prophylactic group; however, there was no statistically significant difference in the HBV DNA levels at reactivation (3.94 × 10⁶ vs 8.30 × 10⁵ copies/ml, P = .47) and the time from first dose of rituximab to HBV reactivation(207 vs 386 days, P = .28). For patients undergoing further rituximab maintanence treatment, the prevalence and mortality of HBV reactivation were 71.4 and 28.6%, respectively. The prevalence and mortality of HBV reactivation are 66.7% vs 75.0% (P = 1.00) and 0 vs 50.0% (P = .43) in lamivudine prophylactic and non-lamivudine prophylactic groups, respectively. The effect of lamivudine prophylaxis on preventing HBV reactivation was found to be less in patients undergoing longer duration of rituximab treatment. A longer duration of rituximab treatment contributed to higher morbidity and mortality of HBV reactivation in HbsAg-positive patients with DLBCL. Further study is warranted for the optimal management of hepatitis caused by HBV reactivation     

COCH predicts survival and adjuvant TACE response in patients with HCC

The aim of the present study was to measure the expression of Cochlin (COCH) and analyze its association with survival, recurrence and the benefits from adjuvant transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC) following hepatectomy. Patients with high COCH expression levels had a poorer prognosis in terms of overall and disease-free survival rate compared with those with low COCH expression levels. Further analysis revealed that patients with low COCH expression who received TACE experienced markedly lower early recurrence rates compared with those who did not receive TACE. However, patients with high COCH expression with and without adjuvant TACE after resection experienced no difference in disease recurrence rates. The expression of COCH was found to be associated with hepatitis B virus infection, portal vein tumor thrombosis and Barcelona Clinic Liver Cancer stage in HCC. Therefore, the findings of the present study indicated that clinical detection of COCH expression may help estimate the prognosis of patients with HCC, as well as determine whether to administer TACE after surgery to prevent recurrence.     

Reactivation of hepatitis B virus and hepatitis C virus in patients with cancer

Infections with hepatitis B virus (HBV) or hepatitis C virus (HCV) are associated with significant morbidity and mortality among patients with cancer, especially in patients with hematologic malignancies and those who undergo hematopoietic stem-cell transplantation. Reported rates of HBV reactivation in HBV carriers who undergo chemotherapy range from 14-72%. In these patients, mortality rates range from 5-52%. HCV reactivation seems to be less common than HBV reactivation and is usually associated with a good outcome and low mortality. However, once severe hepatitis develops, as a result of viral reactivation, mortality rates seem to be similar among patients infected with HBV or HCV. Liver damage owing to viral reactivation frequently leads to modifications or interruptions of chemotherapy, which can negatively affect patients' clinical outcome. Risk factors for the development of severe HBV or HCV reactivation need to be better defined to permit identification of patients who may benefit from preventive measures, early diagnosis, and therapy. In this article, we review the epidemiology, pathogenesis, risk factors, and clinical and laboratory manifestations associated with reactivation of HBV and HCV during immunosuppressive therapy. We also discuss strategies for the prevention and treatment of viral reactivation, including the management of reactivation with new antiviral agents.     

Statistical strategies for HCC risk prediction models in patients with chronic hepatitis B

Risk prediction modelling for hepatocellular carcinoma (HCC) has been the focus of research in the last decade. The prediction models would help HCC risk strati...     

Effect of hepatitis B virus DNA replication level and anti-HBV therapy on microvascular invasion of hepatocellular carcinoma

Background

With few exceptions, current chemotherapy and radiotherapy protocols only obtain a slightly prolonged survival with severe adverse effects in patients with advanced solid tumors. In particular, most solid malignancies not amenable to radical surgery still carry a dismal prognosis, which unfortunately is also the case for relapsing disease after surgery. Even though targeted therapies obtained good results, clinical experience showed that tumors eventually develop resistance. On the other hand, earlier attempts of cancer immunotherapy failed to show consistent efficacy. More recently, a deeper knowledge of immunosuppression in the tumor microenvironment (TME) allowed the development of effective drugs: in particular, monoclonal antibodies targeting the so-called immune checkpoint molecules yielded striking and lasting effects in some tumors. Unfortunately, these monoclonal antibodies are not effective in a majority of patients and are ineffective in several solid malignancies. Furthermore, due to their mechanism of action, checkpoint inhibitors often elicit autoimmune-like disease.

Main body

The use of viruses as oncolytic agents (OVs) was considered in the past, while only recently OVs revealed a connection with immunotherapy. However, their antitumoral potential has remained largely unexplored, due to safety concerns and some limitations in the techniques to manipulate viruses. OV research was recently revived by a better knowledge of viral/cancer biology and advances in the methodologies to delete virulence/immune-escape related genes from even complex viral genomes or “to arm” OVs with appropriate transgenes. Recently, the first oncolytic virus, the HSV-1 based Talimogene Laherparepvec (T-VEC), was approved for the treatment of non-resectable melanoma in USA and Europe.

Conclusion

OVs have the potential to become powerful agents of cancer immune and gene therapy. Indeed, in addition to their selective killing activity, they can act as versatile gene expression platforms for the delivery of therapeutic genes. This is particularly true for viruses with a large DNA genome, that can be manipulated to address the multiple immunosuppressive features of the TME. This review will focus on the open issues, on the most promising lines of research in the OV field and, more in general, on how OVs could be improved to achieve real clinical breakthroughs in cancers that are usually difficult to treat by immunotherapy.