羟基喜树碱明胶微球肝动脉化疗栓塞治疗肝肿瘤的实验研究

目的：对羟基喜树碱明胶微球（ＯＰＴ－ｍｓ）进行栓塞特性的实验研究。方法：以草犬为实验对象，比较了肝动脉注射常规型ＯＰＴ，空白明胶微球和ＯＰＴ－ｍｓ对大鼠肝癌的作用，并以肝动脉注射生理盐水作对照。结果：发现微球栓塞后血管造影可见末梢动脉有不同程度的减少，３０ｄ复查未见侧支循环形成。ＡＫＰ，ＧＰＴ在肝动脉灌注后３ｄ可达到最大值，７ｄ后明显下降，１４ｄ恢复正常，肝功能指标与微球的剂量呈正相关。病理检查有局限性或小灶性坏死，其程度与范围与剂量的大小有关，其它主要脏器无明显改变。结论：ＯＰＴ－ｍｓ对于肝肿瘤治疗是理想的。     

Gd—DTPA增中磁共振成像在诊断肝细胞肝癌中的价值

目的：评价Ｇｄ－ＤＴＰＡ增强磁共振成像在诊断肝细胞肝癌中的价值。资料与方法：经手术病理或临床证实的肝细胞肝癌５３例行磁共振检查，成像序列为：自旋回波Ｔ１ＷＩ，脂肪抑制ＰＤ、Ｔ２ＷＩ及Ｇｄ－ＤＴＰＡ增强Ｔ１ＴＩ（Ｔ１ＷＩ＋Ｃ）。总结各序列图像对瘤体、子灶、假包膜、肿瘤镶嵌样结构、门静脉瘤栓等结构显示率。结果：Ｔ１ＷＩ、Ｔ２ＷＩ、Ｔ１ＷＩ＋Ｃ对瘤体的显示率分别为６６％、１００％、６６％，显示的子灶数分     

经皮冠状动脉内球囊成形术后血管活性物质的变化

本文分析了２５例冠心病患者在ＰＴＣＡ前，ＰＴＣＡ后１ｄ，３ｄ和７ｄ的血浆ＥＴ、ＣＧＲＰ、ＳＰ和ＮＰＹ变化，发现ＥＴ由ＰＴＣＡ前的２１．４１±４．０１ｎｍｏｌ／Ｌ增加到ＰＴＣＡ后的４７．７６±１４３５ｎｍｏｌ／Ｌ，（Ｐ＜００１）在ＰＴＣＡ后３ｄ和７ｄ逐渐回降；ＣＧＲＰ由ＰＴＣＡ前的２．９５±１．２１ｎｍｏｌ／Ｌ增加到ＰＴＣＡ后的１７．９６±３．３４ｎｍｏｌ／Ｌ（Ｐ＜００１），在ＰＴＣＡ后３ｄ和７ｄ逐渐回降至术前水平；ＳＰ在ＰＴＣＡ后３ｄ和７ｄ明显降低；ＮＰＹ由ＰＴＣＡ前的１５２±０２７ｎｇ／Ｌ增加到ＰＴＣＡ后的３．４７±１２ｎｇ／Ｌ（Ｐ＜００１），在ＰＴＣＡ后３ｄ已回降至术前水平。认为ＰＴＣＡ术可以引起体内血管活性物质的变化，这些变化可能与ＰＴＣＡ并发证有关。     

肝动脉栓塞与经肝静脉逆行栓塞联合应用的实验研究

目的：为了使肿瘤及载瘤肝段完全坏死，获得介入性肝段（叶）切除的效果，作者进行了肝动脉栓塞与经肝静脉逆行栓塞（ＴＨＡＥ－ＲＨＶＥ）联合应用的动物实验。材料和方法：８只健康犬进行了ＴＨＡＥ－ＲＨＶＥ，肝动脉栓塞时用带囊导管阻断区域肝静脉后，向相应区域肝动脉注入碘化油，再注入明胶海绵碎片；逆行栓塞肝静脉时，在球囊阻断肝静脉下注入无水酒精－泛影葡胺（１１）混合剂。对照组（单纯肝静脉逆行注入酒精）４只。术后复查肝功能、ＣＴ，定期处死实验动物，行肝脏及肺病理学检查。结果：ＴＨＡＥ－ＲＨＶＥ及对照组技术均成功，实验组与对照组肝功能指标均呈一过性增高。ＣＴ复查显示实验组碘油充填栓塞区肝段及所属门脉分支。实验组术后１周病理检查，栓塞区肝段呈完全性、凝固性坏死，肝静脉、门静脉分支壁厚，其内充满机化血栓，２周时坏死周围有肉芽组织及炎症细胞浸润，４～８周栓塞肝叶明显萎缩，坏死区逐步为纤维组织取代。对照组肝段呈不完全性凝固性坏死，范围较小。结论：ＴＨＡＥ－ＲＨＶＥ方法安全，能获得选择性肝叶（段）切除的效果，可用于单发性巨块型肝癌的治疗。     

碘油／无水乙醇肝节段性栓塞的犬实验研究

目的：研究碘油／无水乙醇肝节段性栓塞术后肝脏的病理变化过程,及此过程中肝、肾功能的改变,为临床推广应用提供依据。材料和方法：以健康杂种犬为实验对象（n=12),碘油／无水乙醇（Lp/E,比例4;1）作为栓塞剂,行肝节段性栓塞,术前、术后监测血常规、淀粉酶、肝肾功能,术后定期复查肝动脉造影、CT并分批处死实验犬进行肝肺组织学检查。结果：术后定期复查肝动脉造影示靶肝动脉均明确闭塞。病理检查发现肝栓塞区小动脉血栓形成,1周后血栓机化,术后4周栓塞肝组织完全坏死,坏死肝细胞完全崩解,代之以纤维组织增生。术后1天白细胞出现一过性升高,术后1周即恢复术前水平。肝功能呈一过性损害,术后1－3周恢复术前水平,主要表现为ALT、AST、γ－GT、ALP和TBA的升高。结论：Lp/E具有确实的栓塞效果,能达到“内科性肝段切除”的目的。     

肝动脉注入羟基喜树碱明胶微球对大鼠移植性肝癌的疗效研究

目的：为了观察羟基喜树碱明胶微球（ＯＰＴ－ｍｓ）的疗效，我们建立了大鼠移植性肝癌模型。材料与方法：以肝动脉注射生理盐水作对照，比较了肝动脉注射常规型ＯＰＴ（１ｍｇ／ｋｇ），空白明胶微球（１０ｍｇ／ｋｇ）和ＯＰＴ－ｍｓ［１０ｍｇ（含药１ｍｇ）／ｋｇ］治疗大鼠肝癌的作用。结果：接受常规ＯＰＴ、空白明胶微球治疗的大鼠，其肿瘤生长受到显著抑制（Ｐ＜０．０５），肿瘤组织发生不同程度的坏死，但与对照组相比动物的生存期未显著延长（Ｐ＞０．０５），而接受ＯＰＴ－ｍｓ治疗的大鼠，其肿瘤的坏死更彻底、更广泛，且动物的生存期明显延长（Ｐ＜０．０１）。结论：ＯＰＴ－ｍｓ疗效明显优于常规型ＯＰＴ单纯肝动脉化疗和空白明胶微球的单纯肝动脉栓塞。     

高压氧对肝硬变患者肝储备功能的影响(论著)

目的：观察高压氧（ＨＢＯ）对肝硬变患者肝储备功能的影响。方法：将３８例肝硬变患者按肝功能Ｐｕｇｈ等分级方法［１］分为肝功能良好组（ｎ＝１８）和损害组（ｎ＝２０）。于ＨＢＯ治疗前及治疗后６、１２天进行口服葡萄糖耐量试验（计算服糖后１２０、６０分钟血糖浓度比值即ＯＧＴＴＲ１２０／６０），检测血清前白蛋白（ＰＡ）、白／球蛋白比值（Ａ／Ｇ）、总胆红素（ＴＢｉ）、凝血酶原时间（ＰＴ）及靛青绿１５分钟潴留率（ＩＣＧＲ１５），根据以上检查结果判断ＨＢＯ治疗对肝储备功能的影响。结果：ＨＢＯ可明显提高Ａ／Ｇ值及ＰＡ水平，降低ＯＧＴＴＲ１２０／６０、ＴＢｉ及ＩＣＧＲ１５，对ＰＴ亦有明显改善及控制作用。结论：ＨＢＯ可提高肝硬变患者肝储备功能，是肝硬变患者术前准备的有助方法     

Gd-DTPA在诊断卵巢肿块中的应用及评价

目的：正确评价Ｇｄ－ＤＴＰＡ在诊断卵巢病变中的作用。材料和方法：采用ＭＲ的Ｔ２加权成像（Ｔ２ＷＩ）和增强前后Ｔ１加权成像（Ｔ１ＷＩ）３种序列，对具有手术病理结果的７５例１１０个卵巢肿块进行回顾性分析。结果：静注Ｇｄ－ＤＴＰＡ后有以下变化特征：（１）恶性肿瘤特征显示正确率由８３．３％升至１００．０％。（２）良、恶性肿块的实质均有明显强化，其强化率之间无显著性差异（Ｐ＞０．０５）；不同强化时程，绝大多数病变的强化率也无明显差异（Ｐ＞０．０５）。（３）２２例手术病理明确分期的恶性肿瘤患者中，常规平扫Ｔ１ＷＩ及Ｔ２ＷＩ，分期正确率为５９．１％，运用造影剂后升至７７．３％，结合ＭＲＩ的３个序列可达８１．８％。结论：Ｇｄ－ＤＴＰＡ可改善对肿瘤的描述和对其内部结构的显示，提高对恶性肿瘤诊断及分期的正确率，但Ｇｄ－ＤＴＰＡ增强无特异性，尚不能依据信号的强化程度来判断病灶的性质，恰当的选择使用对临床具有重要的指导意义。     

肝癌合并门脉癌栓的化疗栓塞治疗

１２８例肝癌合并门脉癌栓病人经２次以上插管治疗，Ａ组肝动脉内灌注化疗药物，Ｂ组药物灌注加碘油栓塞，Ｃ组化疗加碘油及明胶海绵粒栓塞。三组１年生存率分别为２５．００％，２８．５２％，４１．７６％，平均生存７．２个月、８．４个月及１０．３个月。Ｃ组疗效最好，１例病人存活达７年，说明、门脉癌栓不应是肝动脉化疗栓塞的禁忌证，对没有严重肝硬化及肝功能损害的门脉癌栓病人均应进行化疗栓塞治疗。     

外磁场控制磁性明胶微球肝动脉栓塞的实验研究

本实验随机使用杂种犬１７只。磁性明胶微球（ＭＧ－ｍｓ）粒径１０～３０μｍ。含ｘ－Ｆｅ＿２Ｏ＿３３０％（Ｗ／Ｗ）。血管造影、放射性核素扫描、ＣＴ扫描以及病理组织学检查，均显示出磁性明胶微球通过外磁场导向控制，在肝动脉内具有明显的靶向栓塞作用。栓塞术后，血清ＡＬＴ、ＡＳＴ、ＡＬＰ短时间内升高，２～３天达高峰，尔后下降，于３～４周内恢复到术前水平。末发现不良反应及异位栓塞。     

去甲斑蝥素明胶微球肝节段性栓塞的犬实验研究

目的:研究去甲斑蝥素明胶微球肝节段性栓塞术后肝脏的病理变化过程,及此过程中肝肾功能的改变,为临床推广应用提供依据。方法:以健康杂种犬为实验对象(n=8),去甲斑蝥素(NCTD)明胶微球(直径约200μm)与60％泛影葡胺混和液作为栓塞剂,行肝节段性栓塞,术前术后监测血常规、淀粉酶、肝肾功能,术后定期复查肝动脉造影、CT,术后1d及1、2、4周分批处死实验犬进行肝肺组织学检查。结果:术后定期复查肝动脉造影示靶动脉均有不同程度的闭塞,术后病理检查发现肝栓塞区小动脉血栓形成,1周后血栓机化,栓塞肝组织以灶性坏死为主,坏死肝细胞完全崩解,代之以纤维组织增生。术后1d白细胞出现-过性升高,术后2周恢复至术前水平。肝功能呈-过性损害,术后2-3周恢复,主要表现为ALT和ALP的升高。结论:直径为200μm的NCTD明胶微球为一种有效的新型动脉栓塞剂。     

Experimental study of ferromagnetic induction heating combined with hepatic arterial embolization for treatment of liver tumors

The induction heating to ferromagnetic implants (Ferromagnetic Induction Heating: FIH) has been developed for the purpose of selective hyperthermia on deep-seated tumors. In this investigation, the procedure of FIH combined with hepatic arterial embolization (HAE) was experimentally studied on VX2 liver tumor of rabbit. The induction heating unit is composed of radiofrequency generator (500 KHZ, 6-12 KW) and circular applicator (60 cm in diameter). Ferromagnetic implant used was pure iron particles (100 mu in size), which were suspended in tenacious polysaccharide solution to be injectable through a needle. After HAE with gelatin sponge powder had been made, iron particle suspension was injected into the cavity of tumor with subsequent exertion of induction heating (9KW) for 15 minutes. The measurement of temperature was made on the tumor and the liver parenchyma by fluoroptic thermometer with thin, flexible probe which readily passed through a needle. The temperature measured at peripheral area of tumor elevated at range from 2.5 to 7.1 degrees C, corresponding to the dose of iron particles injected; 2.5 degrees C with 1 g, 4.9 degrees C with 2 g, 7.1 degrees C with 3 g. In contrast, the temperature of liver parenchyma elevated at range of less than 2.5 degrees C, to indicate a successful selective heating of liver tumor. An additional experiment for the effect of heat on normal liver of rabbit were made using a microwave heating system. The histological and serologic examinations after heating of below 40 degrees C did not show any abnormal findings. After heating of 42-43 degrees C, however, serum GOT and GPT transiently elevated more than 3 times to that of before heating. Histologically, there were extensive degeneration and necrosis of liver tissue. From the results we concluded that FIH combined with HAE could provide an intensive therapeutic effect for treatment of well-localized liver tumors with minimal damages to the liver parenchyma, because of selective heating of the tumor.     

经导管血管内栓塞治疗肝动脉假性动脉瘤的疗效观察

目的 评价血管内栓塞治疗肝动脉假性动脉瘤(HAPA)的疗效和对肝功能的影响.资料与方法 8例HAPA患者行选择性腹腔动脉造影明确动脉瘤的部位后,再超选择至载瘤动脉进行血管内栓塞治疗.栓塞术后随访3～60个月,观察临床和肝功能情况.结果 8例血管造影均明确诊断.其中肝外型4例,肝内型4例;7例用弹簧圈或微弹簧圈栓塞,1例单纯明胶海绵颗粒栓塞.栓塞术后造影复查8例HAPA均消失.动脉瘤破裂出血患者出血均停止.阻塞性黄疸的患者术后1周黄疸消褪.1例单纯明胶海绵颗粒栓塞者术后3天出血复发;7例钢圈栓塞者无出血和HAPA复发,影像学复查4例HAPA消失,3例HAPA缩小、机化.肝功能检查,2例转氨酶一过性轻度升高[谷-草转氨酶(AST)达286 U/L,谷-丙转氨酶(ALT)达103 U/L)],2例栓塞前肝功能异常栓塞后1周恢复正常;余4例肝功能无异常改变.结论 弹簧圈血管内栓塞治疗HAPA疗效好、并发症少.选择性肝动脉弹簧圈栓塞,对肝功能无明显影响.     

Dependency of tissue necrosis on gelatin sponge particle size after canine hepatic artery embolization

Purpose To determine the optimal size of gelatin sponge particles (GSPs) to produce maximum tumor necrosis with minimum side effects after canine hepatic artery embolization (HAE). Methods GSPs were separated into four size ranges: A, up to 200 μm (mean 152) as Gelfoam powder; B, 200–500 μm (mean 336) as Gelfoam powder; C, 500–1000 μm (mean 649) as Spongel; and D, 1000–2000 μm (mean 1382) as Spongel. Three mongrel dogs were assigned randomly to HAE with each particle size. On day 7 after HAE, the livers were removed and subjected to pathological examination. Results The mean volume of liver necrosis was 11% after embolization, with particle size A, 36.3% with B, 0% with C, and 1% with D. Coagulation necrosis was found in all livers with particles of sizes A and B, and in 1 of 6 with sizes C and D. Bile duct injury was found in five of six dogs with sizes A and B and in none with sizes C and D. Gallbladder necrosis was found in one dog with size B and pancreas necrosis in one with size A. Conclusion GSPs of 500 μm are considered optimally effective for tissue necrosis according to this model.     

Usefulness of dopamine administration after transcatheter hepatic arterial embolization based upon portal hemodynamics]

We evaluated usefulness of dopamine administration after transcatheter hepatic arterial embolization (TAE) for the prevention of hepatic failure in experimental and clinical study. In experimental study we measured portal blood flow in dogs with doppler catheter before and after TAE. Administration of dopamine after TAE increased portal blood flow significantly. In a clinical study the usefulness of dopamine was investigated in a clinical laboratory test. It revealed that serum GOT and GPT improved earlier with dopamine administration after TAE. In conclusion dopamine increased portal blood flow and decreased hepatic parenchymal damage after TAE.     

Influence of hepatic arterial embolization on diabetic patients with hepatocellular carcinoma

Uncontrollable change of diabetes mellitus (DM) has occurred in one of our patients who had received hepatic arterial embolization (HAE) for hepatocellular carcinoma (HCC). This prompted us to examine the influence of HAE to the diabetic patients with HCC. Thirty-four patients accompanying DM who had received HAE were examined fasted blood glucose (FBG) and the liver function before and after the procedure. HAE was performed using Gelatin Sponge and Lipiodol containing anticancer agents, either alone or combined. Of 34 patients 6 showed increase of FBG level of more than two times after HAE. The FBG level had a tendency to elevate as the grade of DM advanced. The tendency was also recognized on pre-HAE oral glucose tolerance test. However, FBG elevation had no relation to the changes of liver function (GPT, Choline Esterase), the difference of embolic materials and pre-HAE status of DM control. From the results, one must be aware that HAE or Lipiodol infusion to diabetic patients with HCC sometimes may cause uncontrollable change of DM, especially in case of advanced DM patients. Consequently, careful follow-up of HCC as DM is advisable for improvement of the patients' prognosis.     

Transcatheter hepatic arterial embolization with avitene in dogs

The hepatic arteries in 36 dogs were embolized with microfibrillar collagen (Avitene) to evaluate the effects on the liver parenchyma. Serial examinations were then conducted over 4 weeks. The dogs were divided into 3 groups: Group 1 received Avitene soaked in saline, Group 2 received decanted Avitene, and Group 3 received Avitene decanted and filtered through gauze. Coagulation necrosis and degeneration of the liver parenchyma was noted in all 3 groups, but was least in Group 3. These results in dogs suggest that gauze filtration of Avitene prior to arterial embolization may also reduce damage to liver parenchyma.     

Hepatocellular necrosis, apoptosis, and proliferation after transcatheter arterial embolization or chemoembolization in a standardized rabbit model

Purpose

To evaluate the effect of transcatheter arterial chemoembolization versus transcatheter arterial embolization on hepatocellular damage, apoptosis, proliferation, and proinflammatory response in a rabbit VX2 tumor model.

Materials and Methods

Rabbits implanted with VX2 tumors in left liver lobes were randomly divided into three groups: a control group (n = 9) that underwent infusion of distilled water into the left hepatic artery, an embolization group (n = 15) that underwent left hepatic artery embolization with polyvinyl alcohol (PVA) particles, and a chemoembolization group (n = 15) that underwent left hepatic artery infusion of a mixture of 10-hydroxycamptothecin and iodized oil followed by PVA embolization. Serum and liver samples were collected at 6 hours, 3 days, and 7 days postoperatively. Liver damage was measured by liver function tests and histologic analysis. Ki-67 immunohistochemistry and terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick-end labeling were performed to quantify proliferating and apoptotic cells. Serum tumor necrosis factor (TNF)–α levels were measured to assess proinflammatory response.

Results

Compared with embolization, chemoembolization caused liver injury with a greater increase in serum alanine aminotransferase and aspartate aminotransferase levels on days 3 and 7; histologic analysis showed increased hepatic necrosis in adjacent liver tissue beginning at day 3 and increased serum levels of TNF-α at 6 hours. By contrast, chemoembolization resulted in a slower increase in hepatocyte proliferation. Additionally, increased apoptotic hepatocytes were observed after embolization and chemoembolization.

Conclusions

In contrast to embolization, nonsuperselective transcatheter arterial chemoembolization increased hepatocellular damage and stimulated systemic proinflammatory cytokine release, but inhibited hepatocyte proliferation.     

Effects of hepatic artery embolization with lipiodol and gelatin sponge particles on normal swine liver

In order to evaluate the effects of hepatic artery embolization (HAE) with Lipiodol (Lp) and gelatin sponge particles (GSP) on swine liver tissue, we embolized the hepatic arteries of 3 pigs with GSP, 9 with Lp, and 9 with Lp+GSP. None of the pigs embolized with GSP died spontaneously during the 4-week experimental period. One pig embolized with 1 ml/kg Lp and three pigs with 2 ml/kg Lp died within 2 h. Two pigs embolized with 0.5 ml/kg Lp+GSP died the following day. The portal vein pressure (PVP) and wedge hepatic vein pressure (WHVP) values before HAE, immediately after, 1 h after, and 4 weeks after HAE showed no remarkable change in the GSP group. Remarkable and temporary elevation was observed in the more than 0.2 ml/kg Lp group. Remarkable and continuous elevation was observed in the 0.2 ml/kg Lp+GSP and 0.5 ml/kg Lp+GSP groups. Gross and histological studies demonstrated no liver damage in the GSP and Lp group. Liver infarction, circular coagulation necrosis with pseudocapsule, and liver atrophy were found in the Lp+GSP group 4 weeks after HAE. The incidence of infarction, circular coagulation necrosis, and liver atrophy in the livers embolized with 0.2 ml/kg Lp+GSP and 0.5 ml/kg Lp+GSP were 67%, 100%, and 75%, respectively. In conclusion, when the hepatic artery is embolized with Lp+GSP, the volume of Lp should be limited to less than 0.1 ml/kg.     

Resolution of Hepatic Encephalopathy Following Hepatic Artery Embolization in a Patient with Well-Differentiated Neuroendocrine Tumor Metastatic to the Liver

Hepatic encephalopathy is considered a contraindication to hepatic artery embolization. We describe a patient with a well-differentiated neuroendocrine tumor metastatic to the liver with refractory hepatic encephalopathy and normal liver function tests. The encephalopathy was refractory to standard medical therapy with lactulose. The patient’s mental status returned to baseline after three hepatic artery embolization procedures. Arteriography and ultrasound imaging before and after embolization suggest that the encephalopathy was due to arterioportal shunting causing hepatofugal portal venous flow and portosystemic shunting. In patients with a primary or metastatic well-differentiated neuroendocrine tumor whose refractory hepatic encephalopathy is due to portosystemic shunting (rather than global hepatic dysfunction secondary to tumor burden), hepatic artery embolization can be performed safely and effectively.