CT引导肝脏特殊位置恶性肿瘤的局部消融治疗

目的 评价在CT引导下经皮肝穿刺局部消融治疗肝脏特殊位置恶性肿瘤的临床应用价值.方法 36例肝脏恶性肿瘤患者,共有45枚肿瘤,所有患者肿瘤数目≤3个,直径≤3 cm,分别位于心脏大血管旁、近膈面、肝门部、肝包膜下、胆囊旁以及结肠旁等肝内特殊部位.使用方法包括微波、射频及无水酒精消融术,根据情况选择单一或联合应用治疗方法,随访12～84个月,观察并发症和疗效.结果 所有患者45枚肿瘤,其中8枚进行了微波治疗,20枚进行了射频治疗,10枚进行无水酒精局部注射治疗,7枚进行了射频联合无水酒精局部注射治疗.未出现任何严重并发症.45枚肿瘤均完全坏死.结论 本组研究结果表明,肝脏特殊位置恶性肿瘤数目≤3个,直径≤3 cm,根据情况选择方案进行CT引导局部消融治疗是一种安全、可行、有效的治疗方法.     

超声引导经皮瘤内注射醋酸治疗肝癌的实验研究和临床应用

目的研究不同试剂对肝组织的坏死能力及对机体的影响。评价超声引导经皮瘤内注射醋酸治疗肝癌的有效性。方法新西兰兔40只,分为5组,分别于肝实质内注射10％盐酸、10％氢氧化钠、50％和75％醋酸以及无水酒精。观察肝脏的坏死大小和肝肾功能变化。原发性肝癌25例,于超声引导下经皮瘤内注射醋酸进行治疗。结果10％盐酸、10％氢氧化钠和75％醋酸造成肝脏坏死的大小均大于50％醋酸和无水酒精,50％醋酸大于无水酒精。术后肝、肾功能的变化组间无差别。24例肝癌经1～2个疗程后,完全缓解达41.6％,部分缓解达33．4％,稳定者25％,全部病例生存皆超过6个月,1年生存率为90％。所有病例均未见严重并发症。结论10％盐酸、l0％氢氧化钠、75％醋酸均可以替代无水酒精对肝肿瘤进行介入治疗。经皮瘤内注射醋酸是一种安全而有效的治疗肝癌新方法。     

彩色多普勒血流显像法引导下原发性肝癌酒精介入性治疗

目的　探讨彩色多普勒血流显像法 ( CDFI)引导介入注射无水酒精治疗肝癌的适应证及疗效。方法　对 2 8例 3 5个肝癌结节在 CDFI引导下行无水酒精注射治疗 ( PEI) ,酒精注入量根据瘤体大小按公式计算。结果　直径≤ 5 cm的肝癌内部组织成分单一 ,酒精容易在其内部得到完全浸润 ,使癌细胞完全溶解、变性 ,癌组织缺血、坏死和纤维化 ,并最终由周围正常肝实质所修复。当 >5 cm的肿瘤 ,由于包膜溃破呈弥漫浸润型方式生长 ,注入肿瘤的酒精极易向瘤区外扩散 ,引起附近正常肝组织坏死 ,加剧患者肝功能的损害。对中、晚期肝癌有黄疸、腹水、凝血机制差、肝功能衰竭倾向者 ,不宜用本法。结论　通过 CDFI引导经皮经肝注入酒精治疗肝癌的临床应用认为该法适用于手术不能切除的小肝癌 ,根据临床随访观察 ,具有肯定的疗效 ,可作为肝癌局部治疗的新途径     

超声引导经皮瘤内注射醋酸治疗肝癌的实验研究和临床应用

目的 研究不同试剂对肝组织的坏死能力及对机体的影响。评价超声引导经皮瘤内注射醋酸治疗肝癌的有效性。方法 新西兰兔４０只,分为５组,分别于肝肾功能变化,原发性肝癌２５例,于怕引导下经皮瘤内注射模型的进行治疗。结果 １０％盐酸、１０％氢氧化钠和７５％醋酸造成肝脏坏死的大小均大于５０％醋酸和无水酒精,５０％醋酸大于无水酒精。术后肝、肾功能的变化的变化组间无差别。２４例肝癌经１～２个疗程后,完全缓解达４１     

经皮无水酒精注射治疗小肝癌的疗效分析（附18例报告）

目的　评估经皮注射无水酒精治疗小肝癌的疗效。方法　 1 8例原发性肝癌 2 2个病灶 (直径 <3.3cm)接受经皮注射无水酒精的治疗。在 CT引导下将细针穿入病灶中央 ,缓慢地注入无水酒精。随访采用螺旋 CT增强扫描的办法进行 ,同时观察并发症发生情况。结果　 2 1个病灶平均肿瘤直径 2 .3cm (1 .5～ 3.3cm ) ,平均注射酒精量 5 .8ml (3～ 9ml)。 1 7个病灶治疗后肿瘤组织全部坏死 ,4个病灶显示有残留肿瘤。并发症包括腹部剧痛(5 .5 5 % )、肝节段性梗塞 (5 .5 5 % )。结论　经皮注射无水酒精治疗小肝癌是安全有效的     

50例肝囊肿无水酒精注射的疗效分析

目的加强对肝囊肿的诊断和抽液无水酒精囊内注射治疗工作的开展。方法以B超诊断、B超导引或B超定位抽取囊液,根据囊肿大小注射无水酒精10～100mL,5～7d复查B超,如肝囊肿内仍有囊液,可再重复抽液注射,直至囊内无积液为止。最多5次抽液注射,即可治愈。结果50例非寄生虫性肝囊肿,明确诊断后,进行抽液再用无水酒精囊内注射,注射量根据囊肿大小和每次注射后吸收情况确定,每次使用无水酒精10～ 100mL,5～7日重复一次。50例患者囊肿直径大于4cm以上,最大直径为26cm,小囊肿·次治愈个别肝囊肿最多5次治愈,治愈率100％。多发性肝囊肿先从最大开始治疗,每次治疗一个结论以B超诊断非寄生虫性肝囊肿,经抽液后注射无水酒精,疗效肯定,经济、方便、简单易行。     

超声引导经皮肝内注射CHML实验研究

目的　验证亲细胞非均质分子脂质 ( CHML )兔肝内注射的生化及病理改变并证实其作用机制 ,探讨 CHML与无水酒精混合应用的效果。方法　取 2 1只实验用兔分 A组 ( CHML组 ) ,超声引导下肝内注射 CHML0 .5 ml;B组 ( CHML+无水酒精组 ) ,超声引导下肝内注射 CHML 0 .2 5 m l+无水酒精 0 .2 5 ml;C组 (无水酒精组 ) ,超声引导下肝内注射无水酒精 0 .5 ml。术前、术后 3天、 1周抽查肝功能、肾功能 ,术后 1周将兔处死 ,取肝、肾、肺行病理检查。结果　 A组肝内坏死病灶 0 .76± 0 .3 2 cm ,B组坏死灶 1.0 1± 0 .2 6 cm ,C组坏死灶 1.15± 0 .4 cm ;B组与 A组比较 P<0 .0 5 ,C组较 B组 P>0 .0 5 ;术后 3天、 1周与术前肝功能、肾功能比较 ,P>0 .0 5 ;而 C组肝功能术后 3天有改变 ,P<0 .0 5 ;病理表现肝细胞完全坏死 ,纤维包膜形成完全 ,而 CHML组有明显管道内皮损伤及脂质沉积及增生改变。结论　 CHML是一种安全的肝内注射硬化剂 ,与无水酒精混合应用效果更佳。     

B超导向病灶内注射无水酒精治疗肝癌

自从日本学者报道了病灶内注射无水酒精治疗小肝癌,取得良好效果后,临床上逐步广泛地应用此法治疗肝癌。酒精与细胞原生质相遇,能使蛋白质脱水沉淀和凝固。我院通过动物实验和尸解观察,发现肝癌及正常肝组织经无水酒精注射后,局部呈灰白色或灰黄色,组织呈无菌性坏死、纤维硬结,结缔组织增生,边界清楚、有的肿块周边形成包膜,其内无正常肝细胞及肿瘸细胞。有人在注射前、后进行肝动脉造影,发     

B超引导下经皮无水酒精注射治疗中晚期肝癌——(附20例报告)

我们自1987年1月以来,在B 超引导下局部注射无水酒精治疗中晚期肝癌20例,兹报道如下。临床资料经治20例,共73例次,最少者1次,最多者12次,平均每例接受4次,一次酒精注射量8～34ml。注射前超声观察肿瘤位于肝右叶12例,位于肝左叶及肝门部8例,肿瘤分别表现为弥漫型、巨块型和多发型,直径最小6cm,最     

超声介入注射无水酒精量化治疗肝癌的临床价值探讨(附32例报告)

目的探讨超声介入注射无水酒精量化治疗肝癌（HCC）的临床价值。方法对32例经病理证实的肝癌在超声引导下行无水酒精注射治疗（PEI），每周2次，4～8次为一疗程，随访12～36个月，观察1、2、3年的生存率及原位与异位复发率。结果32例HCC经无水酒精治疗后，B超示：61．9％肿瘤结节直径缩小，平均直径从3．6cm降为2．7cm；11．9％肿瘤结节消失。肿瘤直径≤3cm组1、2、3年生存率分别为94．4％、83．3％与66．6％，高于直径〉3cm组的85．7％、64．3％与42．9％；1、2、3年复位复发率前者分别为0％、6．7％与8．3％，明显低于后者的7．1％、11．1％与33．3％；异位复发率肿瘤直径≤3cm组分别为11．1％、13．3％与16．7％，也明显低于直径〉3cm组的14．3％、22．2％与50．0％。结论超声介入注射无水酒精治疗HCC疗效可靠，尤其是肿瘤≤3cm者疗效更好，且副作用小、简便、价廉，有较高的临床应用价值。     

Comparison of the metabolism of ethylene glycol and glycolic acid in vitro by precision-cut tissue slices from female rat, rabbit and human liver

1. The metabolism of [1,2-(14)C]-ethylene glycol and [1,2-(14)C]-glycolic acid was studied in vitro using precision-cut tissue slices prepared from the livers of female Sprague-Dawley rats, New Zealand white rabbits and humans. The time-course for production of metabolites formed from ethylene glycol at concentrations from 3 to 40 mM was determined to compare quantitatively the differences between species in the rates and amounts of formation of glycolic acid, the presumed developmental toxicant of ethylene glycol. The rates of metabolism of glycolic acid to glyoxylic acid at concentrations from 0.05 to 16 mM by liver tissue from the different species were also determined. The apparent V(max)/K(m) for the metabolic conversions of ethylene glycol to glycolic acid and for glycolic acid to glyoxylic acid in liver tissue from the different species were obtained. 2. There were qualitative differences in the metabolic profiles and quantitative differences in the formation of glycolic acid between the mammalian liver systems. There was an average of 10-fold less glycolic acid produced by liver slices from rabbits compared with rats. With the human liver, the formation of glycolic acid was not detectable using tissue from three of four human donors. A low level of glycolic acid was detected in one liver slice incubation from one of the four subjects, but only at one extended time point; glyoxylate was detected with liver slices from all four humans. 3. Liver slices prepared from female Sprague-Dawley rats, female New Zealand White rabbits and three female human subjects all metabolized glycolic acid to glyoxylic acid. Human liver tissue was the most effective at further metabolizing glycolic acid to glyoxylic acid. The ratios of V(max)/K(m), representing the relative clearance of glycolic acid from liver tissue, were approximately 14:9:1 for human, rat and rabbit liver, respectively. 4. Precision-cut liver slices maintained in dynamic organ culture are good predictors of metabolism by liver tissue in vivo. The results of the present study therefore indicate that levels of glycolic acid, if formed in vivo, following exposures to similar concentrations of ethylene glycol, would be lower in humans than in rabbits and rats.     

Ethanol and psychotropic drug interaction during pregnancy and lactation

Prolonged maternal ethanol consumption for 8 days during pregnancy or for five days immediately after birth resulted in 30-46 per cent inhibition in the rate of chlorpromazine metabolism by the rat fetal and neonatal livers respectively. A significant increase in hepatic NADH/NAD and UDPG/UDPGA ratios was observed in suckling neonatal and maternal livers from the ethanol-fed group. Acute administration of ethanol with chlorpromazine led to about 60 per cent inhibition of the metabolism of chlorpromazine. This inhibitory effect of ethanol on the metabolism of chlorpromazine was largely abolished by preincubation of liver homogenates with pyrazole (2 mM). Lactate (10 mM) addition to liver homogenates resulted in a significant inhibition of chlorpromazine metabolism. It is suggested that maternal ethanol consumption during preganancy and lactation inhibits the hepatic metabolism of drugs such as chlorpromazine which require glucuronidation for their detoxification. This ethanol-mediated inhibition is largely exerted through the decrease in the NAD-dependent conversion of UDP-glucose (UDPG) to UDP-glucuronic acid, (UDPGA).     

Comparison of the metabolism of ethylene glycol and glycolic acid in vitro by precision-cut tissue slices from female rat,rabbit and human liver

1.?The metabolism of [1,2-¹⁴C]-ethylene glycol and [1,2-¹⁴C]-glycolic acid was studied in vitro using precision-cut tissue slices prepared from the livers of female Sprague—Dawley rats, New Zealand white rabbits and humans. The time-course for production of metabolites formed from ethylene glycol at concentrations from 3 to 40 mM was determined to compare quantitatively the differences between species in the rates and amounts of formation of glycolic acid, the presumed developmental toxicant of ethylene glycol. The rates of metabolism of glycolic acid to glyoxylic acid at concentrations from 0.05 to 16 mM by liver tissue from the different species were also determined. The apparent V_maJK_m for the metabolic conversions of ethylene glycol to glycolic acid and for glycolic acid to glyoxylic acid in liver tissue from the different species were obtained.

2.?There were qualitative differences in the metabolic profiles and quantitative differences in the formation of glycolic acid between the mammalian liver systems. There was an average of 10-fold less glycolic acid produced by liver slices from rabbits compared with rats. With the human liver, the formation of glycolic acid was not detectable using tissue from three of four human donors. A low level of glycolic acid was detected in one liver slice incubation from one of the four subjects, but only at one extended time point; glyoxylate was detected with liver slices from all four humans.

3.?Liver slices prepared from female Sprague—Dawley rats, female New Zealand White rabbits and three female human subjects all metabolized glycolic acid to glyoxylic acid. Human liver tissue was the most effective at further metabolizing glycolic acid to glyoxylic acid. The ratios of F"_max/-/C_m, representing the relative clearance of glycolic acid from liver tissue, were approximately 14:9:1 for human, rat and rabbit liver, respectively.

4.?Precision-cut liver slices maintained in dynamic organ culture are good predictors of metabolism by liver tissue in vivo. The results of the present study therefore indicate that levels of glycolic acid, if formed in vivo, following exposures to similar concentrationsof ethylene glycol, would be lower in humans than in rabbits and rats.     

Effect of ethanol on uptake of trichloroethylene in isolated perfused rat liver

The effect of ethanol on uptake of trichloroethylene in isolated perfused rat liver was investigated. The uptake of trichloroethylene was measured in both phenobarbital (PB) non-treated and PB treated rat livers. Furthermore, for PB treated rat livers, the fluorescence of reduced pyridine nucleotides, oxygen consumption, and scanning reflectance spectrum were measured in the liver, perfused with Krebs-Henseleit buffer saturated with a 92%O2-5%CO2-3%CO gas mixture. The uptake of trichloroethylene was decreased by 6.0% in the PB non-treated rat liver and 10.6% in the PB treated rat liver following the addition of ethanol. This uptake decrease was thought to arise mainly from the inhibitory effect of ethanol on mixed-function oxidation in the liver because of the corresponding decrease in oxygen consumption and absorbance difference delta A450-490nm. The inhibition was considered to be due to interference with electron transfer to the complex of substrate and cytochrome P-450. Increase in intracellular NADH might also affect the formation of trichloroacetic acid since the reduction of NADH in the cytosol attained a maximum with 20 mM ethanol.     

7-ethoxycoumarin O-deethylation in perfused livers from ethanol-fed rats: evidence for an important role of mitochondrial reducing equivalents

Rates of 7-ethoxycoumarin (7EC) O-deethylation in perfused livers were increased approximately 3-fold by chronic ethanol feeding. The acute addition of ethanol (5 mM) and antimycin A (0.03 mM) strongly inhibited 7EC metabolism in perfused livers from ethanol-fed rats, but less inhibition was observed when these agents were added to microsomes or to perfused livers from control rats. The activity of the hepatic pentose phosphate cycle in perfused livers was assessed by comparing 14CO2 release during the infusion of 1-14C-glucose or 6-14C-glucose. 7EC infusion caused a 3-fold greater increase in 14CO2 production from 1-14C-glucose in a liver from a control rat than in a liver from an ethanol-fed rat, indicating greater hepatic pentose cycle activity in livers of control rats. Thus, the pronounced inhibition of 7EC metabolism caused by infusion of ethanol and antimycin A may be explained by a greater dependency on mitochondrial sources of NADPH in livers of ethanol-fed rats. Dinitrophenol (0.05 mM) did not inhibit 7EC metabolism in perfused livers, indicating that a reduction in the cellular redox state, and not diminished energetics, is involved in the mechanism of inhibition produced by antimycin A.     

Gross and microscopic characteristics of liver lesions induced by direct injection of pentobarbital sodium into rats

The hepatotoxic effects of anesthetics brought about by their faulty intraperitoneal application was investigated. Using a syringe with a 26G needle, we injected 0.05 ml/rat of a 50 mg/ml solution of pentobarbital sodium directly into the livers of Sprague-Dawley rats. The animals were killed at 15, 30, or 45 minutes after injection. Massive hemorrhagic necrosis of the liver was seen in all animals injected, while focal necrosis accompanied by inflammatory cell infiltration was observed in the rats killed at 30 and 45 minutes after injection. The histological characteristics of these liver lesions were composed of three types, namely, massive hemorrhagic necrosis, focal cell infiltration separate from the necrosis, and focal necrosis with inflammatory cell infiltration. The infiltrates were composed of both neutrophils and lymphocytes. The characteristic liver lesions closely resembled the hepatic lesions produced by captopril (Helliwel et al., 1985), cyclopiazonic acid (Morrissey et al., 1985), as well as spontaneous liver lesions. The study of serum transaminase levels showed that the elevation of both SGPT and SGOT activities was correlated with the time after injection. Also, a significant increase in the total bilirubin level was noted in all animals treated.     

The role of the hepatocellular redox state in the hepatic triglyceride accumulation following acute ethanol administration

The role of the increased hepatocellular redox-state [( NADH]/[NAD+] ratio) as a mechanism underlying hepatic triglyceride deposition after acute ethanol dosing has been investigated in the rat. Following a single dose of ethanol (2 g/kg i.p.) in fasted rats, increases were observed at 1.5 hr in the hepatic [lactate]/[pyruvate] (133%), [3-hydroxybutyrate]/[acetoacetate] (69%) ratios, and the liver triglyceride concentration (129%). At the same time point, ethanol increased radioactivity incorporated into hepatic total lipid and triglyceride, after an injection of [U-14C] palmitic acid, by 76% and 158% respectively. Treatment of animals with Naloxone hydrochloride (2 mg/kg i.p.) at 1.0 hr and 2.5 hr after ethanol abolished these ethanol-mediated redox-state changes, without inhibiting ethanol oxidation or affecting hepatic acetaldehyde levels. This, however, did not prevent completely the triglyceride accumulation in the liver or reverse the enhanced uptake of radio-labelled palmitate caused by ethanol. Administration of sorbitol (3.5 g/kg i.p.) caused 109%, 57% and 200% increases in the hepatic [lactate]/[pyruvate], [3-hydroxybutyrate]/[acetoacetate] ratios and glycerol-3-phosphate concentrations respectively. However, the hepatic triglyceride concentration and the incorporation of [U-14C] palmitic acid into hepatic lipids were not influenced by this treatment. In vitro studies in which rat liver slices were incubated with [1-14C] palmitic acid also indicated that the altered [NADH]/[NAD+] ratio was not responsible for the decreased rate of fatty acid oxidation seen after ethanol administration or after the addition of ethanol to the incubation medium. In conclusion, these experiments indicate that increases in the hepatic [NADH]/[NAD+] ratio resulting from ethanol oxidation may not be directly implicated in the altered hepatic fatty acid utilisation and triglyceride deposition observed after acute ethanol administration in rats.     

Production of a lesion on liver rough endoplasmic reticulum after prolonged ethanol ingestion and its reversal through abstinence

Prolonged ethanol ingestion by adult rats resulted in an inhibition of amino acid incorporation in vitro by liver membrane-bound ribosomes. The same treatment, however, produced a stimulation in the activity of free ribosomes. The addition of endoplasmic reticulum membranes, extracted from the microsomal fraction of control or ethanol-treated rats, had an inhibitory effect on the protein synthetic activities of free ribosomes. However, the membrane preparations from the livers of ethanol-treated animals had relatively greater inhibitory activity if compared with the similar preparation from the control livers. The observed effect of ethanol intake on liver protein synthesis in vitro could be almost completely reversed if the animals abstained from ethanol for a period of 4 weeks.     

Regulation of NADPH-dependent mixed-function oxidation in perfused livers: Comparative studies with sorbitol and ethanol

Sorbitol and ethanol were shown to have opposite effects on p-nitroanisole O-demethylation in perfused livers from fasted, phenobarbital-treated rats. Sorbitol (2 mM) stimulated drug metabolism by 50% while ethanol (20 mM) caused 80% inhibition. Both sorbitol and ethanol infusion decreased the NAD⁺/NADH ratio and increased fluorescence of pyridine nucleotides monitored from the liver surface; however, the NADP⁺/NADPH ratio was decreased by sorbitol but tended to be increased by ethanol. Stimulation of drug metabolism by sorbitol was abolished by pretreatment of fasted rats with 6-aminonicotinamide, an inhibitor of the pentose phosphate shunt, but was not affected by aminooxyacetate, a transaminase inhibitor. These results indicate that sorbitol stimulated p-nitroanisole metabolism by providing NADPH via the pentose phosphate shunt. Ethanol and sorbitol caused changes in intracellular concentrations of NADPH in livers from fasted rats which correlated directly with changes in hepatic levels of citrate and aspartate. Furthermore, aspartate infusion reduced the inhibition of p-nitroanisole O-demethylation by ethanol. This inhibition was also reversed partially by sorbitol in livers from 6-aminonicotinamide-treated rats. It is concluded that ethanol inhibits mixed-function oxidation primarily by decreasing the concentrations of citric acid cycle intermediates which leads to depletion of cytosolic NADPH.     

Dose-response hapatotoxicity of the peroxisome proliferator, perfluorodecanoic acid and the relationship to phospholipid metabolism in rats.

Perfluorodecanoic acid (PFDA) is a potent peroxisome proliferator that causes hepatotoxicity but lacks tumor-promoting activity in rats. We previously showed that a single dose of PFDA at 50 mg/kg (approximately LD50) causes an elevation in liver phosphocholine (PCho) and other effects related to phospholipid metabolism. In this study, we examined metabolic effects in the dose range 2-50 mg/kg in rats. At doses < or =20 mg/kg, PFDA is significantly less hepatotoxic than the LD50 as manifested by electron microscopy and measurements of daily food consumption and body weight. At 50 mg/kg rat serum tumor necrosis factor (TNF)-alpha concentration was increased 8-fold, while at 15 mg/kg there was no apparent increase in this cytokine. This lower dose, however, induces metabolic effects similar to those seen at the LD50. Liver fatty acyl-CoA oxidase activity showed a dose-dependent increase from 5-25 mg/kg PFDA. Treatments at 15 and 50 mg/kg caused a significant increase in liver phosphatidylcholine (28 and 66%) and phosphatidylethanolamine (31 and 74%). Both doses caused a significant increase in liver PCho but did not affect liver ATP levels, as manifested in 31P nuclear magnetic resonance (NMR) spectra from rat livers in vivo. These data suggest that the increase in liver [PCho] observed following PFDA exposure in rats represents a specific metabolic response, rather than a broad-range hepatotoxic effect.