药物微球对正常和肝癌大白鼠的肝动脉栓塞作用

Experimental hepatic artery embolization with camptothecin (CPT) albumin microspheres was performed in normal livers of 18 rats and experimental hepatic tumors of 8 rats. The effects of drug microsphere embolization were evaluated by selective celiac angiography and pathologic examination. The results showed that hepatic artery and peripheral vessels totally disappeared on angiogram after intra-hepatic-arterial infusion of CPT microspheres. Plentiful collaterals were demonstrable on follow up selective celiac angiogram 20 days postoperative, while partial and complete reconstitution of hepatic artery occurred within 50 approximately 70 days after embolization. Pathologic examination revealed that the drug microspheres were entrapped in the arterioles of liver and scattered areas of infarction were observed in the peripheral parts of liver. Therefore, CPT albumin microsphere is a peripheral type of biodegradable embolizing agent.     

海藻酸钠微球联合肝动脉化疗栓塞治疗原发性肝癌的Meta分析

目的评价国产海藻酸钠微球栓塞剂（KMG）联合肝动脉化疗栓塞（TACE）治疗原发性肝癌的临床效果。 方法：检索Cochrane数据库、PubMed数据库、中国生物医学文献数据库（CBM）、中国期刊全文数据库（CNKI）及万方数据库。检索时间为建库至2016年10月。中文检索词为海藻酸钠、肝动脉化疗栓塞、肝癌。英文检索词为sodium alginate microspheres、hepatocellular carcinoma、transcatheter arterial chemoembolization。搜集公开发表的关于KMG联合TACE治疗原发性肝癌的中英文文献,由3名研究者盲法按纳入与排除标准进行文献筛选和纳入文献的质量评估。使用RevManManger 5.3软件对数据进行Meta分析。 结果按要求共纳入6篇中文文献,共计497例,其中病例组（KMG联合TACE）225例,对照组（单纯TACE）272例。Meta分析结果显示较于TACE,KMG联合TACE能更好地缩小肿瘤体积（OR=4.15, 95%CI:2.38～7.24, P<0.05）;提高患者1年生存率（OR=2.53, 95%CI:1.71～3.75, P<0.05）。但并不能更好地减少术后发热（OR=1.23, 95%CI:0.57～2.69, P=0.60）、术后消化道反应（OR=1.49, 95%CI:0.54～4.15, P=0.44）和术后腹痛（OR=1.39, 95%CI:0.77～2.52, P=0.27）。 结论KMG联合TACE能够缩小病灶和提高患者1年生存率,但对术后栓塞反应无明显改善,具有一定的临床价值。     

微导管在肝动脉化疗栓塞治疗原发性肝癌的临床应用

目的 评价3.0F微导管在肝动脉化疗栓塞治疗原发性肝癌中的临床应用价值，讨论其操作技术和使用适应证。资料与方法 32例原发性肝癌患者采用3.0F SP导管进行化疗栓塞治疗。使用SP导管的原因为：肿瘤肝外侧支供血（n=9)；肿瘤供养血管细小需超选择（n=16)；腹腔干和肝动脉解剖变异（n=6)；肝动脉痉挛（n=1)。结果 32例患者共使用SP导管42次，操作成功39次，失败3次，成功率为92.9%。治疗后AFP下降＞50％者27例（84.4%)，肿瘤病灶缩小＞50%者8例（25％），略有缩小者16例（50％），其余患者肿瘤无明显变化。2例成功进行肿瘤内科性亚肝段切除。全部患者术后均无严重并发症。结论 微导管操作简单、方便，超选择成功率高，特别适用于肿瘤供血动脉严重狭窄、细小，走行迂曲和容易痉挛的患者，在肝动脉化疗栓塞治疗原发性肝癌中有较高的应用价值。     

HepaSphere载药微球与碘油化疗栓塞大肝癌的不良反应比较

目的：比较HepaSphere载药微球与碘化油乳化剂在经导管肝动脉化疗栓塞术（TACE）治疗大肝癌术中及术后的不良反应。 方法：选取广东省人民医院介入科2015年3月—2016年5月行TACE治疗的原发性大肝癌患者129例,其中栓塞材料使用HepaSphere载药微球68例（微球组）,碘化油乳化剂61例（碘油组）,比较两组在TACE术中及术后的不良反应（如发热、疼痛、恶心呕吐）及肝功能情况。 结果：两组术中的常见不良反应为肝区疼痛,微球组的疼痛程度比碘油组轻,差异有统计学意义（P<0.05）;术后常见不良反应为发热、疼痛、恶心呕吐、肝功能下降等,与碘油组相比,微球组发热的程度和术后疼痛的程度均较轻,差异有统计学意义（P<0.05）。肝功能方面,术前及术后3 d两组的白蛋白（ALB）、总胆红素（TBIL）、谷丙转氨酶（ALT）、谷草转氨酶（AST）、凝血酶原时间（PT）水平差异无统计学意义,但术后7 d微球组的AST水平低于碘油组,说明微球组恢复的较快,差异有统计学意义。 结论：对比碘化油乳化剂,应用HepaSphere载药微球行TACE治疗大肝癌,其术中、术后不良反应程度均较轻,术后肝功能恢复较快。     

载药微球经导管肝动脉化疗栓塞治疗肝脏恶性肿瘤研究进展

肝癌是目前临床上常见的消化系统恶性肿瘤,包括原发性肝癌与继发性肝癌,原发性肝癌主要分为肝细胞癌与胆管细胞癌,继发性肝癌则多源于结直肠癌的肝转移。肝癌的治疗手段包括手术切除、肝移植、消融治疗、经导管肝动脉化疗栓塞(TACE)、经肝动脉化疗灌注、靶向治疗及免疫治疗等。根据巴塞罗那分期(BCLC)及中国《原发性肝癌诊疗规范(2019年版)》,TACE可作为无法手术切除的中期肝细胞癌患者的首选治疗方案。随着载药微球的兴起与发展,载药微球-TACE(D-TACE)开始在各个分期的肝癌治疗中崭露头角。本文就TACE尤其是D-TACE在肝细胞癌、胆管细胞癌及肝转移瘤中的应用,TACE与其他治疗方式的临床获益及不良反应,以及TACE治疗后的肿瘤复发和影响预后的分子机制进行综述。     

小剂量与常规剂量化疗药物经动脉化疗栓塞术治疗肝癌的对照研究

目的　探讨经动脉化疗栓塞术 (TACE)中化疗药物的用量对患者生存期与肝功能、术后副反应的影响。资料与方法　 341例肝癌患者 ,随机分为A、B两组 ,分别行TACE术。化疗药物 :A组小剂量组 (16 8例 ) ,丝裂霉素10mg与碘油乳化栓塞。B组常规剂量组 (173例 ) ,给予丝裂霉素 10mg ,5 氟尿嘧啶 10 0 0mg ,表阿霉素 4 0mg ,羟基喜树碱 4 0mg中的 3种联用后碘油与化疗药物乳化剂栓塞 ,随后用明胶海绵粒或聚乙烯醇 (PVA)微球栓塞。TACE术前、术后 3d、7d、2 8d分别行肝功能检查 ,比较丙氨酸转氨酶 (ALT)、天冬氨酸转氨酶 (AST)、总胆红素 (TBIL)、直接胆红素 (DBIL)、白蛋白 (ALB)、白蛋白 /球蛋白比值 (A/G比值 )以及患者术后腹痛、腹胀、恶心呕吐、发热、消化道出血等副反应的发生状况 ,并比较两组患者生存率有无显著差异。结果　两组 1年内平均生存率无明显差异。A、B两组术后 4周内肝功能ALT、AST和A/G比值均无显著性差异 (P >0 .0 5 ) ,术后第 4周 ,A、B两组间比较 ,B组TBIL和DBIL高于A组 ,ALB低于A组 (P <0 .0 5 )。术后腹痛、腹胀、恶心呕吐、发热、消化道出血等副反应的发生率B组明显高于A组 (P <0 .0 5 )。结论　小剂量TACE与常规剂量TACE组患者的生存率没有显著的差异。小剂量TACE对患者的肝功能损伤较     

同轴微导管肝动脉化疗栓塞联合射频消融治疗原发性肝癌

目的 探讨经肝动脉微导管化疗栓塞(TACE)联合射频消融(RFA)术治疗原发性肝癌(HCC)的疗效.方法 回顾分析1000例HCC的DSA表现与术前多层螺旋CT(MSCT)检查结果.其中179例病灶局限于1个肝段,采用微导管超选择插管栓寒.术后4周复查动态增强CT和(或)MR,对40例病灶碘油聚集不良者,进行RFA,术后1个月复查.结果 DSA发现直径3 cm以上肿块670例,3 cm以下病灶202例,子灶400例,动静脉瘘、动门脉瘘482例,异常血供430例,门脉癌栓362例.局限于1个肝段的病灶,微导管栓塞后4周,肿瘤局部控制率为77.6%;控制不良者行RFA后1个月,肿瘤局部控制率为97.5%.结论 DSA对于发现3 cm以下小病灶(含子灶)、肿瘤血供、动静脉瘘、动门脉瘘具有绝对的优势,对HCC的术前评价具有不可替代性的作用.RFA是HCC的有效的治疗方法,是TACE疗效不佳者的理想选择.     

经导管肝动脉栓塞治疗肝癌的护理

我科采用微导管动脉栓塞治疗肝癌，取得满意的效果，现将其护理要点总结如下：     

药物缓释微球TACE对比传统碘油TACE治疗不可切除肝癌：倾向性评分匹配

目的比较药物缓释微球TACE（DEB-TACE）与传统碘油TACE（c-TACE）治疗不可切除肝癌的临床疗效。 方法回顾性分析2015年9与至2020年7月我院治疗120例原发性肝癌的临床资料,其中DEB-TACE组30例、c-TACE组90例。按1∶1进行配对后分析两种治疗方式的临床效果。首要观察指标为患者的肿瘤无进展生存期,次要观察指标是1、3、6、12个月疾病控制、客观缓解率和术后并发症。 结果实际完成配对患者23对,配对后两组间基线特征具有可比性,结果示DEB-TACE相比c-TACE治疗原发性肝癌的中位无疾病进展期分别为3、10个月（P = 0.002）。DEB-TACE组1、3、6、12个月的客观缓解率（69%、78%、60%、52%）明显高于c-TACE组客观缓解率（39%、39%、26%、8%） （P < 0.05）。DEB-TACE组术后3个月的疾病控制率95%明显高于c-TACE组73%（P < 0.05）。术后肝脓肿患者1例（DEB-TACE组1例）,引流后患者恢复良好,余均无严重并发症发生。 结论DEB-TACE治疗不可切除性肝癌在肿瘤控制方面优于c-TACE,具有更好的临床获益。     

载药微球化疗栓塞治疗巨大扁桃体鳞癌1例

扁桃体癌是口咽部最常见恶性肿瘤,以鳞状细胞癌多见,易发生颈部淋巴结转移。外科切除、放疗是其主要治疗手段。对于瘤体巨大、侵犯较广泛者,外科切除困难或不能切除;即使外科切除,因切除范围较大、涉及移植皮瓣,会影响患者生活质量。而放化疗疗效欠佳,难以减轻瘤负荷。     

TACE联合125I放射性粒子植入治疗肝细胞癌门静脉癌栓

目的：探讨TACE联合125I放射性粒子植入治疗肝细胞癌（HCC）门静脉癌栓（PVTT）的方法及疗效。方法纳入TACE联合CT引导下植入125I放射性粒子治疗的HCC合并PVTT患者48例。根据PVTT部位,分为门静脉主干癌栓（A型）、门静脉一级分支癌栓（B型）和门静脉二级及以下分支癌栓（C型）。根据粒子是否植入到PVTT内,分为癌栓内直接植入法（癌栓内部植入组）和癌栓周围植入法（其粒子植入到癌栓周围1．7 cm内的肝实质或肿瘤内,癌栓周围植入组）。比较不同类型PVTT及不同植入方法的癌栓控制率（DCR）、癌栓进展时间（TTP）及患者总生存率（OS）。结果48例患者均成功进行TACE及粒子植入治疗。A、B、C型PVTT患者,中位OS（mOS）分别为8、11．5和15个月,组间差异有统计学意义（P=0．003）;癌栓DCR分别为61．5%、70．8%和72．7%（P=0．548）,肝内肿瘤DCR分别为69．2%、75．0%和81．8%（P=0．483）;癌栓中位TTP分别为4．5、8和11个月（P=0．030）,肝内肿瘤中位TTP分别为5、9和9．5个月。癌栓内部植入组和癌栓周围植入组的mOS分别为10和11．5个月（P=0．239）;癌栓DCR分别为69．2%、68．2%（P=0．591）,肝内肿瘤DCR分别为73．1%和77．3%（P=0．502）;癌栓中位TTP分别为7和10个月（P=0．276）,肝内肿瘤中位TTP分别为8和9．5个月（P=0．089）。结论 TACE联合125I放射性粒子植入治疗HCC伴PVTT,可有效控制PVTT和肝内肿瘤进展,延长患者生存期;癌栓内直接植入法和癌栓周围植入法,对PVTT的疗效无影响。     

Transarterial chemoembolization for hepatocellular carcinoma with drug-eluting microspheres

Purpose

To investigate the efficacy of transarterial chemoembolization (TACE) with microspheres (HepaSphere) loaded with doxorubicin in patients with hepatocellular carcinoma (HCC).

Materials and methods

From April to December 2013, 50 patients with HCC were treated by selective TACE using HepaSphere microspheres loaded with doxorubicin. The size of the lesions was from 2 to 9 cm (mean 5.2).

Results

All of the procedures were technically successful, and there were no major complications. At 1-month follow-up, there was complete tumor response in 48%, partial response in 42%, stable disease in 10%, and there were no cases of disease progression. At 3-month follow-up, complete tumor response was observed in 42%, partial response in 38%, stable disease in 16%, and progressive disease in 4%. At 6-month follow-up, there was complete response in 40%, partial response in 36%, stable disease in 10% and progressive disease in 14%.Within the initial 6-month follow-up, TACE with HepaSphere was successfully repeated once in 3 patients, whereas 2 patients underwent the procedure twice.

Conclusion

Chemoembolization using doxorubicin-loaded HepaSphere is a safe and effective treatment of HCC as demonstrated by the low complication rate, and increased tumor response. When complete tumor response is not achieved, additional treatments can be performed without difficulties.     

肝动脉化疗栓塞治疗中碘油用量的现状与研究进展

肝动脉化疗栓塞治疗已成为不可切除性肝癌的重要治疗方法,而到目前为止,碘化油的应用剂量尚无客观标准,多依靠术者的经验而定。本文分析了常规TACE与超常规剂量TACE的优劣,并对碘油剂量术前量化的可行性展开综述。     

TACE联合索拉非尼治疗BCLC-C期肝细胞癌20例疗效分析

目的 评价TACE联合索拉非尼治疗BCLC-C期HCC的疗效,为临床选择合理的治疗方案提供依据.方法 回顾性分析2008年8月-2014年1月有完整资料的BCLC-C期HCC病例76例,按照不同治疗方法分为3组,其中A组单纯TACE组29例,B组TACE联合索拉非尼组20例,C组支持治疗组27例.观察指标主要为:中位总生存时间(MOS),中位肿瘤进展时间(MTTP),疾病控制率(DCR),3、9和15个月生存率.结果 3组的MOS分别是9.2,12.6和3.1个月(P＜ 0.01); MTTP分别为3.2,5.6和1.5个月(P＜0.01);1～2个月内的DCR分别是82.8％,85.0％和14.8％(P＜ 0.01);3个月生存率分别为100％,100％和51.9％(P＜ 0.01);9个月生存率分别为51.7％,85％和0(P＜ 0.01);15个月生存率分别为10.3％,40％和0(P＜ 0.01).但是A组与B组的DCR、3个月生存率相比较,差异无统计学意义(P＞0.05).结论 对于BCLC-C期HCC,TACE联合索拉非尼疗效最优;对于无法联合治疗的患者,单纯TACE优于支持治疗.     

Transarterial chemoembolization with drug-eluting beads in patients with hepatocellular carcinoma: response analysis with mRECIST

PURPOSEAccording to the Barcelona Clinic Liver Cancer (BCLC) staging classification, transarterial chemoembolization (TACE) is the treatment of choice for intermediate hepatocellular carcinoma (HCC). Thereby, the use of drug-eluting beads (DEB) as embolic agents has been recently established in clinical practice. The aim of this study was to evaluate tumor response after DEB-TACE.METHODSThis retrospective study was approved by the institutional ethics committee. Overall, 89 patients with HCC (Child Pugh A or B) receiving DEB-TACE as palliative treatment option or as bridging before liver transplantation were included in the study. Tumor response was assessed by modified response evaluation criteria in solid tumors (mRECIST) and a tumor growth rate. Survival analysis was performed using Kaplan-Meier estimator with log-rank testing and Cox proportional hazards.RESULTSA total of 188 TACE procedures were performed between 2006 and 2010. After the last intervention, 18% achieved complete response, 45% achieved partial response, 28% had stable disease and 9% had progressive disease. Using the tumor growth rate, 90% of all patients showed a tumor reduction between first and final response evaluation. The 6-month, 1-, 2- and 3-year overall survival rates were 86.5%, 67.4%, 47.2%, and 33.7%, with a median survival of 45, 24, 15, and 14 months for complete response, partial response, stable disease, and progressive disease, respectively. Tumor reduction showed a positive effect on survival.CONCLUSIONDEB-TACE offers conclusive response results with mRECIST and proves a strong tendency of tumor reduction on survival benefits. Therefore, tumor growth rate represents a possible parameter to predict survival.

Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third deadliest cancer in industrialized countries (1). The relevance for HCC is rising by its increase of incidence which is attributed to a higher occurrence of hepatitis B and C as well as to a growing number of alcohol-associated liver diseases and to the epidemic of metabolic syndrome (2, 3). Taking this into account, as well as late diagnosis and very poor prognosis, prevention and treatment of HCC represents the main focus of research.The clinical staging system according to the Barcelona Clinic Liver Cancer (BCLC) classification was introduced by Llovet in 1999 and was updated by Forner in 2010, assigning 5 stages according to tumor burden, liver function, and physical condition that are referred to treatment indications (4, 5). With improved surveillance programs nowadays, diagnosis at an initial stage is feasible for 30%–40% of the patients. Still most patients are diagnosed at intermediate and advanced stage and can therefore only be considered for noncurative treatment options (6). Especially patients at intermediate stage (BCLC-B) benefit from transarterial chemoembolization (TACE) which is the only noncurative treatment, combined with systemic chemotherapy of sorafenib, lenvatinib or regorafenib, that shows to improve survival (7–9).TACE protocols differ widely among centers in regard to technique and chemotherapeutics. In particular the choice of embolic agents is of great scientific interest, as the lipiodol-based conventional TACE (cTACE) is being questioned to release chemotherapeutics in an unregulated high amount to the bloodstream (10). The recent development of drug-eluting beads (DEB) as embolic microspheres, which release high-dose chemotherapeutics in a more controlled way over several weeks, makes them a favorable object of study (11).To assess therapy success and its connection to survival, the adequate selection of response criteria is crucial. This led us to our current retrospective investigation, analyzing tumor response criteria after DEB-TACE in HCC patients and identifying possible survival benefits among response groups.     

球囊辅助TACE术治疗肝癌1例

临床资料 患者男,28岁.因“腹胀、腹泻1个月余,血便1d”入院.既往有慢性乙型肝炎病史.入院体检:T 37.1℃,HR 90次/min,R 20次/min,BP 112/66 mmHg.门诊CT提示:①考虑肝左叶原发性肝癌并肝内转移或多中心型肝癌;②腹膜后淋巴结转移,并肝动脉-门静脉瘘;③疑左侧肾上腺转移,建议结合临床;④肝硬化,脾肿大,腹水.入院后予以抑酸、止血、降门脉压等对症支持治疗,并完善胃镜检查.     

中晚期原发性肝癌96例肝动脉化疗栓塞的疗效分析

目的总结肝动脉化疗栓塞术(TACE)治疗中晚期肝癌的疗效。方法 96例无法切除的中晚期肝癌接受了1～7次TACE(平均1.7次),回顾性分析治疗效果和生存率。结果超选择性肝动脉插管成功率97.9%,1例术后1周因门脉高压突发食管胃底曲张静脉破裂大出血死亡,6个月、1、3年生存率分别为95.8%、72.9%和26%。结论 TACE联合其他抗癌治疗能有效地缓解中晚期肝癌症状和延长生存期。     

抗病毒治疗对HBV DNA阴性的乙肝相关肝癌行TACE术后HBV再激活的预防及对预后影响

 目的 观察抗病毒治疗对乙肝病毒(hepatitis B virus,HBV)DNA阴性的乙肝相关肝细胞癌(hepatitis B virus related hepatocellular carcinoma,HBVR-HCC)行TACE术后HBV再激活的预防及预后影响。方法 选取2012-05-01至2014-05-01在武警上海总队医院行肝动脉化疗栓塞术(transarterial chemoembolization,TACE)HBVR-HCC患者60例(血清HBV DNA<500 U/ml),随机分为治疗组(TACE前行抗病毒治疗)30例和对照组(仅行TACE治疗,HBV再激活后行抗病毒治疗)30例。比较两组患者治疗前后血清HBV DNA、肝功能、凝血功能、甲胎蛋白(α-fetoprotein,AFP)及Child-pugh评分变化情况及生存状况。结果 两组患者基线特征差异无统计学意义,治疗组中未出现患者血清HBV DNA转为阳性,对照组中有6例患者血清HBV DNA转为阳性,两组比较差异有统计学意义(χ²=6.486,P=0.011);术后随访期间,肝功能指标与Child-pugh评分在治疗组与对照组之间差异无统计学意义;术后24周及48周,凝血酶原时间(prothrombin time,PT)与AFP在治疗组与对照组之间差异无统计学意义;术后72周及96周,治疗组明显低于对照组,两组比较差异有统计学意义(P<0.05)。治疗组和对照组客观缓解率(objective response rate, ORR)分别为56.7%和50.0%,两组比较差异无统计学意义(χ²=0.268,P=0.605);治疗组和对照组患者疾病控制率(disease control rate,DCR)分别为86.7%和83.3%,两组比较差异无统计学意义(χ²=0.131,P=0.718)。治疗组与对照组1年生存率分别为76.7%和70.0%,两组比较差异无统计学意义(χ²=0.341,P=0.559);2年生存率分别为70.0%和43.3%,两组比较差异有统计学意义(χ²=4.344,P=0.037)。治疗组与对照组中位生存期(median overall survival,mOS)分别为26.1[95%可信区间(confidence interval,CI):23.9~28.1]个月与22.7(95%CI:6.2~39.6)个月,两组比较差异有统计学意义(χ²=4.857,P=0.021);中位疾病无进展生存期(median progression-free survival,mPFS)分别为16.4(95%CI:14.8~17.6)个月与15.1(95%CI:4.6~26.0)个月,两组比较差异有统计学意义(χ²=4.561,P=0.027)。结论 血清HBV DNA阴性的HBVR-HCC患者TACE术前行抗病毒治疗可以防止乙肝病毒再激活,延长患者生存时间,改善预后。     

CalliSpheres载药微球TACE联合微波消融治疗原发性大肝癌疗效评价

目的探讨CalliSpheres载药微球经导管肝动脉化疗栓塞术(TACE)联合微波消融治疗原发性大肝癌的临床疗效。方法23例直径5~10cm原发性肝癌患者施行了CalliSpheres载药微球TACE联合微波消融治疗。术后1、3、6、9、12个月及以后每3个月采用肝脏增强MRI随访。结果23例患者共行33次CalliSpheres载药微球TACE联合微波消融治疗,无肝脓肿、胆脂瘤等并发症发生。23例患者随访3~22(平均9.2±3.9)个月,术后1、3、6、9、12和15个月客观缓解率分别为86.9%、87%、93.8%、77.0%、63.6%、57.2%,疾病控制率分别为100.0%、95.7%、93.8%、92.3%、81.8%、85.7%。术后3、6、9、12和15个月生存率分别为100%、93.8%、84.6%、81.8%、71.4%。结论CalliSpheres载药微球TACE联合微波消融治疗原发性大肝癌安全可靠,近中期疗效较好。