An experimental study on the pathophysiology of stenosis and occlusion in portal vein reconstruction in resection of cancer of the hepatic hilus

An experimental study using mature mongrel dogs was performed to clarify the pathophysiology of stenosis and occlusion of portal vein reconstruction accompanied with hepatectomy. All the animals underwent partial (53%) hepatectomy. They were arbitrarily divided into three groups: Non-stenosis Group I with hepatectomy only, Stenosis Group II with partial '70%) stenosis of the portal vein, and Occlusion Group III with ligation of the portal vein. All cases of Group III died within about 122 minutes. The blood flow and pressure of the portal vein, portography, ICG Rmax and the residual liver weight were serially examined until the fourth week following the operation in Group I and Group II. Two principal results were derived: 1) In Group I, portal circulation was sufficiently restored and the residual liver showed adequate regeneration. 2) In Group II, hepatofugal collateral vessels developed. However, the portal pressure remained significantly high (p less than 0.002) and, the portal blood flow and liver tissue blood flow were markedly reduced (p less than 0.001) for 1 week after operation. The residual liver weight and liver function (ICG Rmax) were significantly decreased even in the fourth week. Recently, portal vein resection accompanied with hepatectomy has been accepted as a procedure for advanced carcinoma of the hepatic hilus. This study suggests that stenosis or occlusion of the portal vein should be avoided in the procedure.     

Experimental studies of transcatheter portal embolization

The effects of transcatheter portal embolization (TPE) on energy charge (EC) and hepatic blood flow of the rat liver (HBF) were investigated. The antitumor effects on minimal tumor nodules inoculated into the rat liver via the portal vein were evaluated by the alphafetoprotein (AFP) levels and survival period after TPE. The EC of the embolized lobes was significantly decreased after TPE, as compared with the control groups, but was restored 3h later. The HBF of the embolized lobes was reduced 1h after TPE, but was restored in 1 day when TPE was performed by means of temporary embolus. When permanent embolus was used for TPE, decreased HBF persisted for at least seven days. On the other hand, HBF of the non-embolized lobes was not altered in both groups. When TPE was performed after TAE using temporary embolus, the intervals of 14 days were required for normal liver tissue to be preserved. TPE performed 3 days after inoculation of cancer cells into the rat liver caused prolongation of the survival period and decrease in the level of AFP. These results indicate that TPE does not produce marked damage to the liver and has antitumor effects on minimal tumor nodules. TAE followed by TPE may be useful for therapy of unresectable liver tumor.     

Beneficial effects of arterialization of the portal vein on extended hepatectomy

BACKGROUND: Extended hepatectomy may result in postoperative liver failure. The aim of this study was to evaluate the effects of arterialization of the portal vein on oxygen supply, hepatic energy metabolism and liver regeneration after extended hepatectomy. METHODS: Portal haemodynamics were evaluated 0 or 10 days after arterialization of the portal vein in three experimental groups: 85 per cent partial hepatectomy, 85 per cent partial hepatectomy 10 days after arterialization of the portal vein and 85 per cent partial hepatectomy 10 days after ligation of the hepatic artery. Survival rates, weight of the regenerating liver, levels of adenine nucleotides and hepatic energy charge were assessed. RESULTS: Arterialization of the portal vein caused a significant increase in partial pressure of oxygen and oxygen saturation. Portal blood flow 10 days after arterialization was significantly increased. Survival rate and weight of the regenerating liver in the group with arterialization of the portal vein were significantly higher than those in the other two groups. The group with arterialization of the portal vein showed the highest levels of adenosine 5'-triphosphate. CONCLUSION: The increase in portal blood flow and oxygen supply produced by arterialization of the portal vein has beneficial effects on hepatic energy metabolism and liver regeneration, and leads to improved survival after experimental extended hepatectomy.     

Effect of partial portal vein ligation on hepatic regeneration

To evaluate the effect of portal hypertension and diminished portal venous blood flow to the liver on hepatic regeneration, male rats were subjected to partial portal vein ligation and subsequently to a two-thirds partial hepatectomy. The levels of ornithine decarboxylase activity at 6 h after partial hepatectomy were greater (p less than 0.001) in the rats with prior partial portal vein ligation than in those without portal hypertension. The rats with prior partial portal vein ligation also had greater (p less than 0.005) levels of thymidine kinase activity at 48 h after partial hepatectomy than did those without portal hypertension. Hepatic sex hormone receptor activity was not affected by prior partial portal vein ligation either before or after partial hepatectomy. The reductions in both estrogen and androgen receptor activity observed in the hepatic cytosol after partial hepatectomy were similar to those observed in control animals. These data indicate that animals with portal hypertension having a diminished hepatic portal blood flow have a normal capacity to regenerate hepatic mass following a hepatic resection.     

肝切除时门静脉血部分动脉化的研究

目的 研究犬门静脉血部分动脉化的肝保护作用。方法 建立大保留肝（占全肝６０％）暂时性血流阻断、肝固有动脉切断并切除未阻断肝的急性肝衰模型（对照组）,并行肝总动脉与胃十二指肠静脉吻合（Ａ－Ｐ组）,观察生存率并定时测定丙氨酸转氨酶（ＡＬＴ）、动脉血酮体比（ＡＫＢＲ）及肝动脉脉、门静脉血气分析。结果 对照组７天生存率为３７．５％,Ａ－Ｐ组均较差异有非常显著性（Ｐ〈０．０１）,门静脉和肝静脉血氧分压均较术     

扩大肝部分切除术后入肝门静脉动脉化对大鼠血流动力学的影响

目的对大鼠行扩大肝部分切除术后利用右肾动脉行入肝门静脉动脉化加门腔分流术,研究该术式对大鼠门静脉血流动力学的影响。方法 Sprague-Dawley大鼠130只,分为A组(动脉化组)47只,行70%扩大肝部分切除术后,用右肾动脉行门静脉动脉化加门腔分流术;B组(肝切组)43只,行70%扩大肝部分切除及右肾切除,阻断门静脉10min;C组(对照组)40只,仅行右肾切除及门静脉主干游离。分别于术后第2、7、14、28天检测门静脉压力、内径和血流量。结果 A组及B组手术成功率分别为85.1%和93.0%,差异无统计学意义,C组手术成功率100%。术后各时间点A组与B、C组比较,入肝门静脉压力、门静脉内径、血流速度和入肝血流量变化均较后两组更明显(P0.01);A组入肝门静脉压力随时间推移有下降趋势,于术后第14天(12.7±0.7)cmH2O达到稳态,与术后第28天(12.4±0.6)cmH2O比较,差异无统计学意义;而A组门静脉内径、血流速度和入肝血流量在术后各时间点间相比差异无统计学意义。B组术后门静脉血流速度均较C组增快(P0.05),门静脉血流量在术后14～28d较C组增加(P0.05)。结论大鼠扩大肝部分切除术后行入肝门静脉动脉化模型稳定可靠,手术成功率理想,动脉化术后门静脉压力明显升高,门静脉内径出现扩张以适应压力变化,入肝血流量明显增加。门静脉血流动力学指标在术后早期即发生改变并取得稳态。     

活体供肝者术后门静脉血栓形成的诊治二例

目的 总结活体供肝者术后门静脉血栓形成的诊治体会.方法 2名活体供肝者,术前螺旋CT评估门静脉分型为B型门静脉和A型门静脉,经估算,残肝体积分别为全肝体积的33%和36%,均切取带肝中静脉的右半肝.术后早期丙氨酸转氨酶(ALT)和总胆红素升高,腹腔引流液较多,呈腹水样,超声波检查提示门静脉血栓形成,并经增强螺旋CT明确诊断.供者1急诊行探查术,阻断门静脉血流,拆除闭合残端缝线,将门静脉切断,切除狭窄处门静脉壁,开放门静脉主干,取出多块新鲜血栓,用肝素盐水冲洗至血流通畅后,再将其端端吻合,恢复血流.供者2给予抗凝和溶栓治疗.结果 供者1在手术探查后再次发生门静脉血栓形成,经抗凝和溶栓治疗后血栓消失,痊愈出院.供者2经保守治疗后血栓消失,痊愈出院.结论 门静脉血栓形成可依据超声波及CT等影像学检查结果作出诊断,可采取手术取栓或抗凝、溶栓治疗.     

The experimental study on the temporary portal vein arterialization in the canine liver transplantation: preliminary report

To evaluate the feasibility of temporary portal vein arterialization (PVA) in orthotopic partial liver transplantation (PLT), we performed 5 canine PLTs with PVA assessing the changes in arterial ketone body ratio (AKBR) as an index of hepatic energy status, and measuring portal pressure and flow. After anastomosis of hepatic vein, the graft liver was revascularized with arterial blood shunted from the external iliac artery to the hepatic side of the portal vein. By using this technique, both anhepatic period of the recipient and ischemic time, especially warm ischemic time, of the allograft were markedly shortened (31.0 +/- 4.5 min: Mean +/- SEM). Four out of 5 recipients survived for at least 5 days (13 days in average). The AKBR was restored immediately after PVA and showed almost the same values as those at preclamping and after completion of anastomoses of both portal vein and hepatic artery. No significant difference in portal venous pressure was observed between during PVA and after vascular reconstruction. Portal blood flow during PVA was about one fourth of the total hepatic blood flow at preclamping. These results suggest that PVA can be used as an alternative procedure in PLT.     

Hepatic effects of influxed endothelin-1 from portal vein: in situ portal vein infusion model using dogs

Background/Purpose Endothelin-1 is a potent vasoconstrictor formed by vascular endothelium. This study was designed to investigate the hepatic effect of endothelin-1 produced by portal vascular endothelium. Methods Portal venous pressure, portal venous flow, hepatic arterial flow, tissue blood flow, and tissue oxygen pressure were measured during portal vein endothelin-1 infusion in dogs at rates of 1.0 to 5.0 ng/kg per minute. Sinusoidal width during maximal infusion was determined morphometrically. Serum concentrations of mitochondrial glutamic oxaloacetic transaminase and endothelin-1 in portal and hepatic venous blood were also measured. Results Intraportal endothelin-1 infusion dose-dependently increased portal venous pressure and reduced portal venous and hepatic arterial blood flow. Tissue blood flow and oxygen pressure also decreased. Endothelin-1 also significantly increased serum mitochondrial glutamic oxaloacetic transaminase and constricted hepatic sinusoids. These changes reversed after completion of infusion. Conclusions Intraportal endothelin-1 caused circulatory and histological changes in hepatic sinusoids that may suggest the role of endothelin-1 formed by portal venous bed epithelium.     

脾肾静脉分流联合断流术的临床疗效及对门静脉系统血流动力学的影响

目的评价近端脾肾静脉分流加门奇断流联合手术和门奇断流术的临床疗效及对门静脉系统血流动力学的影响。方法回顾性总结近8年采用脾肾分流加门奇断流联合手术和门奇断流术治疗门静脉高压症245例,于术前一周和术后2周应用核磁共振血管造影测量门静脉、脾静脉和肠系膜上静脉的直径,流速和流量,并于术中动态测量门静脉压力。结果联合手术组术后较术前门静脉血流量下降,肠系膜上静脉流量增加,差异有统计学意义(P<0.05),门静脉直径和自由门静脉压下降差异有统计学意义(P<0.01)。联合手术组与断流组相比,门静脉血流量的减少差异没有统计学意义,而自由门静脉压的下降差异有统计学意义(P<0.01)。联合手术组术后再出血率明显低于断流组,而肝功能和脑病发生率两组间差异无统计学意义。结论联合手术可结合断流和分流手术的优点,既明显降低出血率又不增加脑病发生,应成为治疗门静脉高压症合并出血的首选术式。     

Combined portal vein and liver resection for biliary cancer]

Portal vein resection has become common in hepatobiliary resection for biliary cancer with curative intent. When cancer invasion of the portal vein is very limited, wedge resection followed by transverse closure is indicated. Longitudinal closure is contraindicated, as this procedure causes stenosis of the portal vein. In the case of right hepatectomy, segmental resection is feasible before liver transection. Reconstruction is completed with end-to-end anastomosis, in which an intraluminal technique is used for posterior anastomosis and an over-and-over suture for anterior anastomosis. More than 5-cm resection of the portal vein often requires reconstruction with an autovein graft. In the case of left hepatectomy, portal vein resection after liver transection is preferable. The resection and reconstruction method should be determined based on both the extent of cancer invasion of the right portal vein and the length of the right portal trunk. So far, we have aggressively carried out combined portal vein and liver resection in 106 patients with advanced biliary cancer (62 cholangiocarcinoma and 44 gallbladder carcinoma). Twenty-nine patients underwent wedge resections and 77 segmental resections (66 end-to-end anastomosis and 11 autovein grafting using an external iliac vein). In patients with hilar cholangiocarcinoma (n = 58), 3- and 5-year survival rates were 23% and 8%, respectively. Three patients survived for more than 5 years after resection. In contrast, the prognosis of patients with gallbladder cancer (n = 44) was dismal. All of the patients died within 3 years after surgery, although they survived statistically longer than unresected patients. These data suggest that portal vein resection has survival benefit for patients with cholangiocarcinoma. However, the indications for this procedure in gallbladder cancer should be reevaluated.     

Hepatic and portal vein blood flow during carbon dioxide pneumoperitoneum for laparoscopic hepatectomy

Background: Laparoscopy under carbon dioxide (CO₂) pneumoperitoneum has many advantages. However, the risks of CO₂ pneumoperitoneum during laparoscopic hepatectomy (LH) have not been defined. Methods: The hemodynamics of the hepatic vein were examined during CO₂ pneumoperitoneum both pre- and posthepatectomy in eight pigs. Portal blood flow was measured with Doppler ultrasound during laparoscopic cholecystectomy in 10 human patients. Results: Experimentally, elevated intraabdominal pressure (IAP) with CO₂ insufflation produced significant increases in CO₂ partial pressure and echogenicity of the hepatic vein in the posthepatectomy group. Clinically, elevated IAP caused significant narrowing of the portal vein and significant decreases in portal blood velocity. The mean portal flow was significantly decreased with elevation of IAP >10 mmHg. Conclusions: LH with CO₂ pneumoperitoneum may lead to embolism caused by CO₂ bubbling through the hepatic vein. Elevated IAP may cause a decrease in hepatic blood flow and induce severe liver damage, especially in patients with poor liver function. Gasless laparoscopy using abdominal wall lifting should be employed in LH to avoid the risks of CO₂ embolism and liver damage. Received: 28 March 1997/Accepted: 12 September 1997     

Progressive hepatic arterial flow increase after end-to-side portacaval shunt in normal and cirrhotic rats

Hepatic blood flow (HBF; ml/min/g of liver) has been measured in Wistar rats with a Xenon 133 washout method. The hepatic arterial blood flow (HABF) which amounts to 23 +/- 3% of the total HBF increases immediately after occlusion of the portal vein to ensure 36 +/- 4% of the control HBF, but continues to increase progressively for the next 4 h to furnish 69 +/- 5% of the control HBF. This represents a 183 +/- 16% increase of the control HABF. Thereafter, the liver starts to atrophy, whereas the total liver blood flow remains constant. Thus, the HBF increases and 30 days later does not differ significantly from the control value. Similar experiments were performed in rats in which cirrhosis was induced by CCl4. The HBF is decreased and the contribution of the hepatic artery raised. After portacaval shunting, the increase of the HABF, although less pronounced, is also progressive and takes 4 h to reach its maximum.     

不同肝血流阻断方式在肝癌手术中应用的对比研究

目的　探讨不同血流阻断方法在肝癌手术应用的适应证。方法　回顾性分析 1 991至2 0 0 1年采用不同血流阻断方式进行肝切除 1 5 6例 ,对手术情况及术后肝功能情况进行分析。结果　(1 )球囊导管区域性血流阻断组平均术中输血明显少于PTC法肝门阻断组及半肝血流阻断组。 (2 )术后 1周时患者肝功能比较 ,区域性血流阻断组、Pringle法肝门阻断组、规则半肝切除组的肝功能改变存在统计学差异。结论　 (1 )球囊导管区域性血流阻断肝切除术术中失血少 ,对肝功能影响小。 (2 )球囊导管区域性血流阻断肝切除术是一种简便、安全有效的手术技术。     

Jejunectomy can reduce excessively elevated portal pressure after major hepatectomy in beagle dogs

A number of factors can lead to the life-threatening liver dysfunction in the aftermath of an extended hepatectomy. Prominent among them is the high portal pressure induced by the concentrated flow of the entire stream of portal blood toward the small remnant liver. Twelve beagle dogs were randomly divided into group A (n=6, 70% hepatectomy) and group B (n=6, 70% hepatectomy after jejunectomy). Three dogs in each group were euthanized at 1 or 4 weeks after the operation and examined to evaluate hemodynamic changes, liver functions, and liver histology. One hour after the hepatectomy, the animals in group B exhibited a significantly lower portal pressure (P=0.002) and significantly higher hepatic arterial flow (P=0.004) than the animals in group A. As more time passed, the total hepatic flow and hepatic tissue flow both rose up to levels significantly higher than those in group A (P=0.037 and P=0.025, respectively). The alkaline phosphatase, total protein, albumin, and anti-thrombin III were all significantly better in group B than in group A on the 1st post-operative day. Liver specimens biopsied at 1 h after the hepatectomy showed significantly more swelling of the hepatocytes in group A than in group B. In addition, an immunohistochemical study using the TUNEL method for liver biopsy on the seventh post-operative day revealed numerous positive cells in group A but few in group B. Our results suggest that the portal pressure control by the enterectomy can forestall dysfunction of the remnant liver after extended hepatectomy, especially during the early post-operative period.     

Measurement of portal blood flow in man by a continuous local thermodilution method. III. Effects of dopamine on systemic and portal hemodynamics after hepatectomy

We gave dopamine (3 micrograms/kg/min, 30 min) intravenously on the third day after hepatectomy to 19 patients, and studied the effects of the drug on systemic and portal hemodynamics. In another 42 patients, administration of dopamine at the same rate was started soon after hepatectomy and continued for about 2 weeks; the clinical results were evaluated. After hepatectomy, the systemic hemodynamics were hyperdynamic and the portal hemodynamics were hypodynamic. After 30 min of dopamine administration, the oxygen pressure in portal blood increased, and because portal blood flow also increased, the oxygen delivery to the liver increased. The mechanism involved an increased proportion of portal venous flow to cardiac output, and a decrease in the splanchnic resistance, not portal venous resistance. Probably, specific dopamine receptors played important role in the increase in the superior mesenteric arterial blood flow. Among 42 patients given small dosage of dopamine, the clinical symptoms of five of seven who had developed liver failure improved. None of the other 35 patients given dopamine preventively developed liver failure. Dopamine in small doses is useful for the management of liver failure after liver resection.     

选择性脾胃区减断分流术后血流动力学变化的实验研究

目的 研究门静脉高压症犬行选择性脾胃区减断分流术(selective decongestive devascular-ization shunt of gastrosplenic region,SDDS-GSR)后血流动力学变化.方法 用正常犬制备门静脉高压脾亢模型并进行SDDS-GSR术.制模前、成模后,分流术后30 d和术后60 d观察门静脉压力,门静脉、肝动脉、脾静脉和脾动脉的内径、血流速度和血流量参数的变化,作自身对照研究.结果 SDDS-GSR术后30 d的脾胃区静脉压力显著下降(P<0.01),门静脉、脾动脉和脾静脉内径显著缩小(P<0.01),门静脉、脾动脉和脾静脉血流量参数减少(P<0.01),肝动脉内径和血流量参数显著增加(P<0.01),术后60 d上述指标改变仍保持稳定.结论 sDDS-GSR术通过减少脾动脉血流和改善脾静脉回流,有效地降低了脾胃区的静脉压力,并保持肠系膜区的相对高压,同时增加肝动脉向肝血流量,保证了门脉的向肝血流量,术后血流动力学变化较持久稳定,是一种合理而可取的治疗门静脉高压症的术式.     

门静脉栓塞术在二期精准肝切除中的应用

目的: 探讨门静脉栓塞术在二期精准肝切除的应用。方法: 分析7例在超声扫描及X线数字减影血管造影引导下,经皮经肝穿刺门静脉栓塞术后,行二期精准肝切除术的肝癌病人临床资料。分成肝硬化组3例和无肝硬化组4例,分别检测门静脉栓塞术前和术后肝功能指标及肝体积变化,总结二期手术切除。结果: 7例病人均成功实施经皮经肝穿刺门静脉栓塞术,其中6例病人达到肝脏体积代偿增大的预期效果,顺利完成二期精准肝切除术。1例结肠直肠癌肝转移病人在门静脉栓塞8周后,未栓塞肝脏代偿性增大体积未达到精准肝切除的条件,转外院顺利行拯救性联合肝脏离断和门静脉结扎的二步肝切除术。两组经皮经肝穿刺门静脉栓塞术后1 d,肝功能指标较术前升高（P<0.05）,予护肝治疗3~7 d后降至术前水平。未发生严重并发症。结论: 门静脉栓塞技术成功率高、安全可行。剩余肝脏代偿性增大明显,可显著提高二期精准肝切除手术率。     

限制流量的门静脉动脉化对大鼠肝脏功能和结构的远期影响

目的 探讨限制流量的门静脉动脉化术后门静脉血液动力学改变，以及对肝脏功能和结构的远期影响。方法 建立大鼠门静脉完全动脉化（portal vein arterialization，PVA）以及限制流量的大鼠门静脉动脉化模型，观察术后1及6个月门静脉血流量、横截面积以及术后6个月门静脉压力及肝脏结构和功能的变化。结果 末采取限制流量措施的门静脉动脉化术后门静脉横截面积和血流量随时间延长呈增加的趋势，术后6个月血清ALT水平显著升高（F=7，72，P〈0，01）。肝内门静脉及其分支显著增宽、壁增厚、内膜胶原纤维增多。而限制流量的门静脉动脉化术后门静脉横截面积与血流量增加趋势不显著，血清GPT水平接近正常水平，术后6个月，3组大鼠动脉化门静脉压力、血浆内毒素、动脉血酮体比值以及血清白蛋白、总胆红素和碱性磷酸酶水平差异无统计学意义。结论 门静脉完全动脉化后，限制流量是必要的，保持一定流量的动脉化门静脉血，对于维持肝脏正常生理功能，防止过高血流量对肝脏功能和结构的损害，有重要意义。     

Changes in hepatic ultrastructure and function following portal vein resection with a use of an internal shunt bypass

Experimental studies on ultrastructural and functional changes of mitochondria were carried out using adult dog livers after portal vein resection with an internal shunt bypass. As a comparative study portal vein resection with an external shunt bypass was also carried out. A 10 cm long anti-thrombotic UK catheter was inserted into the portal vein as an internal shunt bypass (internal shunt group). Similarly, a catheter was inserted between the portal vein and inferior caval vein as an external shunt bypass (external shunt group). The time of portal vein shunt bypass was 2 hrs for both groups. During operations, the blood flow of the hepatic artery was blocked. After the bypass was installed, the hepatic artery and the portal vein were declamped. As a control experiment the hepatic artery was clamped without making a shunt bypass (non-shunt group). Left lateral lobe was resected from the liver prior to the shunt implant and then the right lateral lobe was removed 2 hrs after the declamping of the hepatic artery. Biochemical analysis on mitochondria isolated from the livers of the internal and the external shunt groups was carried out. Changes of mitochondrial ultrastructure were also studied using electron microscope. Changes in serum m-GOT and OCT activities were also examined. Essentially no changes were detected in phosphorylating capacities and ultrastructure of mitochondria of the livers obtained from either the external shunt group or the internal shunt group. However m-GOT and OCT activities in the serum were definitely elevated in the external shunt group of animals compared to those in the internal shunt group of animals. This suggests that the permeability of hepatic mitochondrial membranes in the external group of animals was changed probably due to hypoxia. From these results we recommended the application of the internal shunt bypass for hepato-biliary surgery combined with the resection of the portal vein.