肝脏隔离灌注化疗治疗中晚期肝癌研究

实践证明 ,在肝癌的化疗中 ,局部化疗比全身化疗有效。肝脏隔离灌注(ｉｓｏｌａｔｅｄｈｅｐａｔｉｃｐｅｒｆｅｒｕｓｉｏｎ ,ＩＨＰ)治疗 ,作为一种局部化疗的手段 ,与其它局部治疗手段如化疗药物栓塞、冷冻治疗、酒精注射相比 ,具有可以治疗多发性肝癌、巨大肝癌 (直径大于 5ｃｍ) ,有效地降低体循环药物浓度等优点。一、方法原理ＩＨＰ原理是将肝脏的入肝血流和出肝血流通过体外转流装置和体循环隔离开来 ,从入肝血流处注入各种大剂量抗癌药物 (可达正常全身用量的 30～ 50倍 ) ,对肿瘤组织发挥作用。Ａｕｓｍａｎ和Ａｕｓｔ在 1 960年…     

肝癌区域性治疗的新突破——肝脏隔离灌注化疗

我国的肝癌患者约占全世界的 5 0 % ,其死亡率占恶生肿瘤死亡率的第二位。长期以来 ,手术切除一直是肝癌的首选治疗方法 ,但临床诊断明确的肝癌患者多数已属中晚期 ,可行手术切除者不足 2 0 %。近年来随着细胞生物学、影像学、介入放射学的发展 ,各种区域性化疗方法应运而生并迅速发展 ,为肝癌的开辟出新的领域。肝脏隔离灌注 (isolated liver perfusion IL P)化疗作为新近开展起来的技术为肝癌区域性化疗注入了新的活力。1　肝脏隔离灌注化疗的国内外研究进展要是通过阻断肝脏周围血管 ,将肝脏循环隔离于体循环之外 ,然后采用体外循环装…     

肝脏隔离灌注区域化疗治疗肝癌

肝脏隔离灌注区域化疗治疗肝癌邢雪，夏德生应用细胞抑制剂进行器官区域性灌注的原则首先由Ｋｌｏｐｐ提出，５０年代末将此技术加以改进并与体外循环系统联合应用，６０年代初奠定了高温灌注的基础，认为癌细胞对高温极其敏感［１～３］。首例肝脏隔离灌注（ｉｓｏｌａｔ...     

区域隔离肝脏灌注的研究

本研究旨在探讨区域隔离肝脏灌注(RIHP)的可行性 ,并初步评价其隔离效果 ,化疗药物局部积聚效果及肝脏损害情况。一、材料与方法1.动物选择 :幼猪 2 1头 ,随机分为 3组 :经动脉组 (实验A组 ) 7头 ;经动脉和门静脉联合组 (实验B组 ) 7头 ;对照组(C组 ,经肝固有动脉灌注化疗组 ) 7头。3组动物的体重差异无显著性 (P >0 .0 5 )。2 .手术操作 :麻醉后上腹部屋顶形切口进腹 ;A组游离左肝动脉 ,近心端结扎 ,远心端插管 ;解剖出左肝静脉 ,远端阻断 ,近端插管。B组则在左肝动脉插管后 ,继续解剖游离出左门静脉 ,近端阻断 ,远端插管 ,左肝静脉处…     

肝脏隔离高温灌注化疗术的麻醉处理

肝癌是消化系统常见的恶性肿瘤 ,病人就诊时多不是早期 ,不足 30 %的病人能接受手术切除病变肝脏 ,临床治疗效果欠佳 ,寻求治疗肝癌新技术是国内外研究的热点。肝脏隔离灌注高浓度的抗肿瘤药加局部高温 (ｉｓｏｌａｔｅｄｈｙｐｅｒｔｈｅｒｍｉｃｌｉｖｅｒｐｅｒｆｕｓｉｏｎ ,ＩＨＬＰ)是治疗不可切除肝癌的新技术[1 ] ,ＩＨＬＰ手术期间需建立两条体外转流通路 ,对病人的生理干扰大 ,麻醉处理有其特殊性 ,现将我院开展一例ＩＨＬＰ手术的麻醉报告如下。临床资料病人男性 ,5 0岁 ,体重 6 0ｋｇ ,因右上腹胀痛伴纳差、乏力 1个月 ,以原发…     

原位肝脏隔离灌注行肝脏恶性肿瘤区域性化疗的实验研究进展（综述）

本文以肝脏隔离灌注行肝脏区域化疗的实验研究为重点，讨论动物模型的建立，灌注液成分与灌注途径及其实验研究的发展方向。     

经肝动脉区域肝脏隔离灌注的研究

目的　研究幼猪经肝动脉区域隔离肝灌注的效果。　方法　14只幼猪随机分为2组:对照组(7只):采用经肝动脉灌注;实验组( 7只):左肝动脉及左肝静脉插管,进行左肝区域隔离肝灌注。灌注液为氨甲喋呤溶液(1mg/kg), 灌注时间为60min。于灌注5、10、20、30、45、60min时分别抽取外周血、肝脏灌注区域血、肝脏未灌注区域血(实验组)测定血药浓度; 灌注后切取左肝及右肝组织进行病理检查。　结果　在所有时间点, 实验组肝脏灌注区域氨甲蝶呤的血药浓度明显高于非灌注区和外周血(P<0. 01), 60min时最高, 达( 40. 211±3. 756 )μg/ml, 而非灌注区和外周血中仅为(1. 584±0. 347)μg/ml和(0. 773±0. 096)μg/ml。实验组灌注区域血药浓度均高于对照组肝脏血药浓度(P<0. 01), 60min时分别达(40. 211±3. 756)μg/ml和(4. 498±1. 643)μg/ml。实验组灌注区浓度-时间曲线下面积为218. 295μg/ml,而在对照组肝脏仅为260. 860μg/ml。病理检查提示两组灌注肝脏均有肝细胞浊肿、气球样细胞,但实验组肝脏灌注区域肝细胞坏死率为85. 7% (6 /7),明显高于对照组28. 6% (2 /7)。实验组肝脏未灌注区域无明显病理损害。　结论　动物实验证实经肝动脉区域隔离肝灌注是一种灌注及隔离效果好、肝功能损害小的区域化疗方法。     

原位肝脏隔离灌注行肝脏恶性肿瘤区域性化疗的实验研究进展(综述)

本文以肝脏隔离灌注行肝脏区域化疗的实验研究为重点,讨论动物模型的建立,灌注液成分与灌注途径及其实验研究的发展方向。     

肝脏隔离灌注化疗治疗肝脏恶性肿瘤

原发性肝癌在我国常见，手术切除仍是目前能使病人获得无癌长期生存的唯一方法。但由于肝癌缺乏特异性临床表现，且发展迅速，多数病人在确诊时已属中晚期，不仅手术切除率低，术后早期复发率亦高，预后差，因此探讨中晚期肝癌的有效治疗方法，是广大肝外科工作者极感兴趣...     

逆行隔离灌注化疗可减轻对大鼠肝脏的毒性及药物的泄漏

目的 采用大鼠肝脏隔离灌注模型探讨逆行隔离灌注(RIHP)较顺行隔离灌注(IHP)能否减少正常肝组织损伤及化疗药物外周泄漏率.方法 将90只体重300～350 g雄性SD大鼠随机分为A、B、C三组,每组30只:A组为空白对照组,经肝动脉及门静脉灌注乳酸林格液,以下腔静脉为灌注液流出道;B组行IHP,经肝动脉灌注含有350 mg/kg的氟尿嘧啶(5-Fu),门静脉灌注乳酸林格液,以下腔静脉为灌注液流出道;C组行RIHP,经肝动脉灌注含有350 mg/kg的氟尿嘧啶(5-Fu),经下腔静脉灌注乳酸林格液,以门静脉为灌注液流出道.术后1、3、5、7 d分别行血清ALT测定及肝组织病理学检查;高效液相色谱分析仪检测B、C组术中外周血药浓度.结果 三组术后3 d存活率分别为90.0%、86.7%和90.0%,三者差异无统计学意义.三组血清ALT均在术后第一天达到峰值,A组为(481.6±207.6)μmol/L;B组为(1641.6±658.0)μmol/L;C组为(913.0±353.5)μmol/L.B、C组均显著高于A组(P＜0.05);B组显著高于C组(P＜0.05).B组与C组术中外周血药浓度峰值分别为(131.2±29.4)μg/ml和(65.3±28.4)μg/ml.两组外周浓度有显著性差异(P＜0.05).A组术后肝脏病理改变较轻,术后7 d基本恢复正常;B组术后肝脏病理学改变相对严重,术后7 d局部仍可见坏死灶;C组术后肝脏病理改变后较A组严重,但较B组轻,术后7 d基本恢复正常.结论 RIHP较之IHP能够显著减轻化疗药物对正常肝组织的毒副作用和药物的外周泄漏,有望成为一种对肝癌更加有效安全的区域化疗方法.     

经皮选择性肝脏隔离灌注化疗肝细胞形态及凋亡研究

目的探讨经皮选择性肝脏隔离灌注化疗（PSIHP）的可行性及隔离效果。方法实验猪8头，利用介入放射学方法进行经皮选择性肝脏隔离灌注化疗结合血液灌流。化疗药物选用5-Fu。比较灌注及未灌注区域肝细胞形态和凋亡指数。结果灌注区域肝细胞损伤明显，肝细胞凋亡指数（52．83±5．12）明显高于未灌注区域肝细胞凋亡指数（3．52±0．96）（P〈0．01）。结论PSIHP是一种简单有效的肝脏隔离灌注化疗技术，隔离效果佳，对未灌注区域肝组织有良好的保护作用。     

逆行隔离灌注化疗可减轻对大鼠肝脏的毒性及药物的泄漏

Objective The retrograde isolated hepatic perfusion (RIHP) model was used to compare with the isolated hepatic perfusion (IHP) model in reducing the rate of normal hepatic tissue toxicity and peripheral drug leakage during chemotherapy in rat liver. Methods A total of 90 male Sprague-Dawley rats weighing 300-350 g were randomized into 3 groups with 30 rats in each. Group A: perfusion with Lactated Ringer'S Solution through arteria hepatica (RA) and portal vein (PV),the inferior vena cava was used as an outflow tract of perfusate. Group B: For isolated hepatic perfusion (IHP), Fluorouracil (5-FU) was added into the perfusate at a dose of 350mg/kg and introduced in to the liver through arteria hepatica, portal vein was perfused by Lactated Ringer'S Solution, and the inferior vena cava was used as an outflow tract of perfusate. Group C: by using retrograde isolated hepatic perfusion (RIHP), the solution which contains 350 mg/kg Fluorouracil (5-FU) was also introduced through arteria hepatica, the inferior vena cava was introduced with Lactated Ringer'S Solution;the portal vein was used as an outflow tract of the perfusate. On day 1, 3, 5 and 7 after the perfusion in all groups, blood serum ALT test and liver histopathology test were performed. The peripheral blood drug levels were measured with high performance liquid chromatographic(HPLC) system in group B and group C. Results The survival rate was 90%, 86.7% and 90% in group A, B and C,respectively. No statistically significant difference was observed in the survival rate among the 3groups. In all the three groups, serum ALT levels were the highest on the first day after IHP: (481.6±207.6)μmol/LingroupA;(1641. 6±658.0) μmol/LingroupBand( 913. 0±353. 5)μmol/Lin group C. Significant higher serum ALT levels were observed by comparing group B and C with A(P＜0. 05). Meanwhile, the serum ALT levels were significantly higher in group B than in group C (P＜0.05). The peaks of peripheral blood drug concentration during the perfusion were 131.2±29.4μg/ml in group B and 65.3±28. 4μg/ml in group C. Significant difference was observed (P＜0. 05). Liver biopsies of group A showed mild changes on the first day after IHP and returned to normal after 7 days. Group B showed severe changes on the first day after IHP and local necrosis still existed after 7 days. Group C showed moderate changes as compared with group B on the first day after IHP and also returned to normal after 7 days. Conclusion Retrograde isolated hepatic perfusion (RIHP) can reduce the liver toxicity compared to isolated hepatic perfusion (IHP). Hopefully, RIHP will be considered as a safer way in regional chemotherapy in liver cancer.     

逆行隔离灌注化疗可减轻对大鼠肝脏的毒性及药物的泄漏

Objective The retrograde isolated hepatic perfusion (RIHP) model was used to compare with the isolated hepatic perfusion (IHP) model in reducing the rate of normal hepatic tissue toxicity and peripheral drug leakage during chemotherapy in rat liver. Methods A total of 90 male Sprague-Dawley rats weighing 300-350 g were randomized into 3 groups with 30 rats in each. Group A: perfusion with Lactated Ringer'S Solution through arteria hepatica (RA) and portal vein (PV),the inferior vena cava was used as an outflow tract of perfusate. Group B: For isolated hepatic perfusion (IHP), Fluorouracil (5-FU) was added into the perfusate at a dose of 350mg/kg and introduced in to the liver through arteria hepatica, portal vein was perfused by Lactated Ringer'S Solution, and the inferior vena cava was used as an outflow tract of perfusate. Group C: by using retrograde isolated hepatic perfusion (RIHP), the solution which contains 350 mg/kg Fluorouracil (5-FU) was also introduced through arteria hepatica, the inferior vena cava was introduced with Lactated Ringer'S Solution;the portal vein was used as an outflow tract of the perfusate. On day 1, 3, 5 and 7 after the perfusion in all groups, blood serum ALT test and liver histopathology test were performed. The peripheral blood drug levels were measured with high performance liquid chromatographic(HPLC) system in group B and group C. Results The survival rate was 90%, 86.7% and 90% in group A, B and C,respectively. No statistically significant difference was observed in the survival rate among the 3groups. In all the three groups, serum ALT levels were the highest on the first day after IHP: (481.6±207.6)μmol/LingroupA;(1641. 6±658.0) μmol/LingroupBand( 913. 0±353. 5)μmol/Lin group C. Significant higher serum ALT levels were observed by comparing group B and C with A(P＜0. 05). Meanwhile, the serum ALT levels were significantly higher in group B than in group C (P＜0.05). The peaks of peripheral blood drug concentration during the perfusion were 131.2±29.4μg/ml in group B and 65.3±28. 4μg/ml in group C. Significant difference was observed (P＜0. 05). Liver biopsies of group A showed mild changes on the first day after IHP and returned to normal after 7 days. Group B showed severe changes on the first day after IHP and local necrosis still existed after 7 days. Group C showed moderate changes as compared with group B on the first day after IHP and also returned to normal after 7 days. Conclusion Retrograde isolated hepatic perfusion (RIHP) can reduce the liver toxicity compared to isolated hepatic perfusion (IHP). Hopefully, RIHP will be considered as a safer way in regional chemotherapy in liver cancer.     

肝动脉灌注化疗栓塞治疗原发性中晚期肝癌48例

原发性肝癌(HCC)是我国常见的恶性肿瘤，近年来通过普查发现早期HCC的患者，进行以手术治疗为主的综合治疗，疗效显著提高。肝动脉栓塞灌注化疗(transeatheter arterial chemoembolization,TACE)是目前治疗中晚期HCC的有效手段。我们采用5-FU、丝裂霉素(MMC)、顺铂与碘化油充分混合行TACE治疗，取得良好效果。     

血管介入在肝癌中的应用

在我国原发性肝癌是排名第四的常见恶性肿瘤,也是排名第二的肿瘤致死原因。我国60%以上的肝癌病人在初诊时已是中晚期,失去了根治性手术治疗的机会。对于不可切除的肝癌病人,血管介入治疗贯穿其治疗始终。近年来,血管介入治疗在肝癌治疗中取得了显著的成效,笔者将结合国内外研究资料,从血管介入治疗的理论基础、联合其他治疗和发展方向等层面系统性地阐述血管介入在肝癌治疗中的应用。     

经肝动脉与门静脉同时插管灌注化疗治疗晚期肝癌

<正> 1988年5月至2000年5月我们对不能手术切除的31例晚期肝癌患者经肝动脉与门静脉同时插管、间断灌注化疗,临床观察治疗效果尚满意,现总结报告如下。 1 临床资料 1.1 一般资料:31例中男27例,女4例,年龄最小37岁,最大68岁,平均年龄54例。原发性肝癌24例,弥漫性肝癌7例,均经病理诊断证实。 1.2 辅助治疗:为完成整个治疗过程,减少化疗药物抑制造血系统的毒性作用,保护消化功能。本组在化疗灌注的前、中、后同时应用以下辅助治疗:①聚肌胞2ml肌注或静滴2～3次/周。②干扰素1支,肌注1～3次/周。③华蟾素10～30mg     

肝癌用药物输注装置作肝动脉灌注的观察

本文介绍６６例中晚期肝癌埋置药物输注装置作肝动脉和门静脉灌注化疗的长期随访结果。治疗组２９例均为不能切除的肝癌；预防组３７例为姑息性肝切除术后。结果：治疗组中完全缓解２例，部分缓解１１例，轻度缓解４例，无改变１０例，病情发展２例，总有效率４４．８％（１３／２９），中位生存期１５月，二期切除率１３．８％（４／２９）。预防组中肝动脉灌注组无复发，最长已观察５３月；而３例门静脉主干癌栓取出后单作门静脉灌注者均复发，术后１、２、３年生存率分别为６５．７％、５０％、２５％。