门静脉分支结扎后门静脉压力变化与肝再生的关系

目的 探讨90%门静脉分支结扎后大鼠门静脉压力变化与肝再生的关系.方法 45只雄性SD大鼠行90%门静脉分支结扎术,其中5只进行假手术作为对照.观察不同时相点门静脉压力和非结扎侧肝脏质量变化,光学显微镜下观察非结扎侧肝细胞的形态学变化,免疫组织化学方法检测未结扎侧肝细胞的增殖细胞核抗原(PCNA),TUNEL法检测未结扎侧肝细胞的凋亡情况,并进行定最分析.采用Pearson相关分析和t检验分析数据.结果 95%(38/40)的大鼠存活.结扎侧肝叶进行性萎缩,非结扎侧肝叶占全肝质量的比例随时问推移而增加,12 h内增加较缓慢,仅为10.75%;而1～5 d则增加速度明显加快,达到27.57%;7～28 d达到平台期,缓慢增加到32.37%.术前门静脉压力为(9.1±1.8)cm H_2O(1 cm H_2O=0.098 kPa);结扎后立即升高,12 h达到高峰(15.8±2.7)cm H_2O,与术前比较差异有统计学意义(t=6.847,P<0.05);1～28 d由(13.6±2.3)cm H_2O逐渐下降为(9.3±2.0)cm H_2O.术前大鼠PCNA阳性细胞计数为7%±3%,术后12 h至3 d由14%±5%上升至21%±6%,第5天达到高峰为26%±7%,与术前比较差异有统计学意义(t=9.129,P<0.05),随后逐渐恢复正常.TUNEL法检测结果显示,术前大鼠肝脏和术后各时相点大鼠未结扎侧肝脏仅见极少量凋亡细胞.大鼠门静脉压力与非结扎侧肝叶肝细胞PCNA的表达在术后1、3、5 d呈正相关(r=0.913,0.896,0.908,P<0.05),在术后14 d时相点呈负相关(r=-0.926,P<0.05).结论 大鼠90%门静脉分支结扎术后,引起未结扎侧肝细胞的活跃再生,再生后的肝脏可恢复原来的质量;肝再生以肝细胞增殖加速为主,而非肝细胞凋亡减少;门静脉压力变化在肝再生过程中可能发挥重要作用.     

Portal vein embolization vs. portal vein ligation for induction of hypertrophy of the future liver remnant

The objective of this study was to assess the efficacy of right portal vein embolization (PVE) vs. right portal vein ligation (PVL) for induction of hypertrophy of the left lateral liver lobe before extended right hepatectomy. Thirty-four patients with primary or secondary liver tumors and estimated remnant functional liver parenchyma of less than 0.5% of body weight underwent either right PVE (transcutaneous, n= 10; transileocolic, n =7) or right PVL (n=17). Liver volume was assessed by CT scan before occlusion of the right portal vein and prior to resection. There were no deaths. The morbidity rate in each group was 5.8% (PVE, 1 abscess; PVL, 1 bile leak). The increase in liver volume was significantly higher after PVE compared with PVL (188±81 ml vs. 123±58 ml) (P= 0.012). Postoperative hospital stay was significantly shorter after PVE in comparison to PVL (4±2.9 days vs. 8.1±5.1 days;P<0.01). Curative liver resection was performed in 10 of 17 patients after PVE and 11 of 17 patients after PVL. PVE and PVL were found to be feasible and safe methods of increasing the remnant functional liver volume and achieving resectability for extended liver tumors. PVE results in a significantly more efficient increase in liver volume and a shorter hospital stay. Presented at the Forty-Third Annual Meeting of The Society for Surgery of the Alimentary Tract, San Francisco, California, May 19–22, 2002 (oral presentation).     

Effects of portal vein arterialization on liver regeneration after partial hepatectomy in the rat

Although portal venous supply is considered essential to preserve hepatic integrity, in this study, effects of portal arterialization on liver regeneration were evaluated in a rat model of partial hepatectomy (PH). Ninety-six Lewis rats were randomly assigned to four groups of 24 rats each: PH only (group 1), PH with either venous or arterialized portal supply (groups 2 and 3, respectively), and PH without portal supply (group 4). Liver regeneration rate (LRR), 5-bromo-2-deoxyuridine (BrdU) labeling index, and liver biological characteristics were assessed on days 1, 2, 3, and 7. Compared with group 1, all tested rats had a marked body weight loss after surgery, and only rats in group 4 showed no signs of recovery on day 7. With maintained portal inflow (groups 1, 2, and 3), LRRs increased steadily to day-7 values of 89.2% [plusmn] 11.8%, 81.4% [plusmn] 8%, and 77.4% [plusmn] 9.4%, respectively (P = not significant), and 24-hour peak values of BrdU labeling index were 159 [plusmn] 26, 157 [plusmn] 42, and 149 [plusmn] 48, respectively (P = not significant). Conversely, rats deprived of portal supply (group 4) showed profound inhibition of these two parameters (14 [plusmn] 13; P [lt ] .01;32.1% [plusmn] 7.7%; P [lt ] .001, respectively). These results indicate that proper portal blood supply is essential to initiate and maintain liver regeneration after PH. With an equivalent portal inflow rate of either venous or arterial source, the hepatic regeneration response can be sustained. (Liver Transpl 2002;8:146-152.)     

Direct vascular implantation of liver for hepatic regeneration after interruption of the portal vein and hepatic artery

This paper reports an experiment in which nine dogs were subjected to extended partial hepatectomy in addition to interruption of the portal vein and hepatic arterial system. The lobe of the liver which sustained the dog was supplied solely by blood from an extrahepatic vascular source previously implanted directly into the liver parenchyma. It is hoped that the ability of a small segment of liver to regenerate, under these conditions, might prove clinically useful in some patients with tumors of the liver, gallbladder, or extrabiliary system who, by present criteria, are considered inoperable.     

Functional transition: Inconsistently parallel to the increase in future liver remnant volume after preoperative portal vein embolization

BACKGROUNDPreoperative portal vein embolization (PVE) is a widely used strategy to enable major hepatectomy in patients with insufficient liver remnant. PVE induces hypertrophy of the future liver remnant (FLR) and a shift of the functional reserve to the FLR. However, whether the increase of the FLR volume (FLRV) corresponds to the functional transition after PVE remains unclear.AIMTo investigate the sequential relationship between the increase in FLRV and functional transition after preoperative PVE using 3-dimensional (3D) computed tomography (CT) and ^99mTc-galactosyl-human serum albumin (^99mTc-GSA) single-photon emission computed tomography (SPECT) fusion images. METHODSThirty-three patients who underwent major hepatectomy following PVE at the Department of Gastroenterological Surgery I, Hokkaido University Hospital between October 2013 and March 2018 were enrolled. Three-phase dynamic multidetector CT and ^99mTc-GSA SPECT scintigraphy were performed at pre-PVE, and at 1 and 2 wk after PVE; 3D ^99mTc-GSA SPECT CT-fused images were constructed from the Digital Imaging and Communications in Medicine data using 3D image analysis system. Functional FLRV (FFLRV) was defined as the total liver volume × (FLR volume counts/total liver volume counts) on the 3D ^99mTc-GSA SPECT CT-fused images. The calculated FFLRV was compared with FLRV.RESULTSFFLRV increased by a significantly larger extent than FLRV at 1 and 2 wk after PVE (P < 0.01). The increase in FFLRV and FLRV was 55.1% ± 41.6% and 26.7% ± 17.8% (P < 0.001), respectively, at 1 wk after PVE, and 64.2% ± 33.3% and 36.8% ± 18.9% (P < 0.001), respectively, at 2 wk after PVE. In 3 of the 33 patients, FFLRV levels decreased below FLRV at 2 wk. One of the three patients showed rapidly progressive fatty changes in FLR. The biopsy at 4 wk after PVE showed macro- and micro-vesicular steatosis of more than 40%, which improved to 10%. Radical resection was performed at 13 wk after PVE. The patient recovered uneventfully without any symptoms of pos-toperative liver failure.CONCLUSIONThe functional transition lagged behind the increase in FLRV after PVE in some cases. Evaluating both volume and function is needed to determine the optimal timing of hepatectomy after PVE.     

主肝静脉急性阻断后引流肝段保留价值的研究

目的观察主肝静脉阻断后保留肝段的病理形态学变化。方法７８只大鼠随机分为对照组、肝段静脉结扎组、左主肝静脉缩窄组与结扎组,动态观测受累肝叶的病理学,肝脏微循环与血流动力学变化。结果主肝静脉结扎后２４小时即发生肝细胞坏死,门静脉血内毒素与ＴＸＢ２／６－Ｋｅ－ｔｏ－ＰＧＦ１α明显升高,主肝静脉缩窄组受累肝叶边缘大量肝静脉与门静脉侧支形成,门静脉血内毒素与ＴＸＢ２／６－Ｋｅｔｏ－ＰＧＦ１α也发生不同程度升高,两组均明显高于肝段静脉结扎组与对照组。结论正常肝组织不能耐受主肝静脉急性阻断,无肝静脉引流的肝组织不但完全丧失功能,而且引起内毒素血症与肝脏微循环障碍,主肝静脉结扎应同时将引流肝段切除。     

Administration of rhHGF-activator via portal vein stimulates the regeneration of cirrhotic liver after partial hepatectomy in rats

BACKGROUND/AIMS: Cirrhotic liver has less ability to regenerate than normal liver, but it can produce the precursor of hepatocyte growth factor (proHGF) similarly to normal liver after resection. Studies were performed to examine whether the exogenous administration of recombinant human (rh) HGF-activator converts proHGF to biologically active (mature) HGF, inducing an enhancement of liver regeneration in cirrhosis. MATERIALS AND METHODS: Rats with liver cirrhosis were treated by 45% partial hepatectomy, and rhHGF-activator or vehicle was injected via the portal vein 24 h after resection. Liver injury and its regeneration, the conversion of proHGF to mature HGF, and the activation of its signal through HGF receptor (c-Met) were analyzed. RESULTS: rhHGF-activator improved the recovery of liver function after resection in cirrhotic liver as compared with the control group. rhHGF-activator also enhanced the proliferating cell nuclear antigen labeling index and liver regeneration rate. rhHGF-activator converted the proHGF to mature HGF, showing the maximal effect at 10 min after injection, which was followed by tyrosine phosphorylation of insulin receptor substrate (IRS)-1, and the association of IRS-1 with c-Met and phosphatidylinositol 3-kinase. CONCLUSIONS: Results demonstrate that the administration of rhHGF-activator stimulates the recovery of liver function and regeneration after resection in cirrhotic liver through the activation of proHGF and its intracellular signal. It may be potentially useful treatment for patients with liver cirrhosis.     

肝移植术后门静脉狭窄的血管内介入治疗

目的 评价肝移植术后门静脉狭窄的介入治疗的效果及安全性.方法 回顾性分析2004年4月至2012年1月收治的肝移植术后门静脉狭窄患者30例,所有患者均具有门静脉高压的临床症状、体征或经超声检查等影像学检查显示门静脉狭窄.经皮肝穿刺门静脉造影明确门静脉狭窄的部位、范围和程度,球囊扩张后行支架植入.同时行胃冠状静脉造影,如严重曲张或者影响门静脉血流则行栓塞治疗.介入治疗后对患者进行随访,记录患者的临床症状、实验室检查结果及超声检查等影像学检查结果.结果 30例患者均成功接受门静脉造影,其中1例未能通过狭窄的门静脉主干;其余29例中,25例行球囊扩张后支架植入术,共植入26个自膨式支架;4例行球囊扩张治疗.介入治疗的技术成功率为96.7％(29/30).7例行曲张的胃冠状静脉弹簧圈栓塞.介入治疗相关的并发症为胸膜腔出血2例.随访期为1～72个月(平均21.5个月),所有接受介入治疗患者的门静脉均通畅,未出现支架内再狭窄.结论 介入治疗肝移植术后门静脉狭窄安全、有效,门静脉通畅率良好.     

Extracorporeal portal vein oxygenation improves outcome of acute liver failure in swine.

BACKGROUND: Portal vein arterialization (PVA) has shown efficacy to treat acute liver failure (ALF) in preclinical studies. The next step is to perform large animal studies that propose a clinically acceptable method of PVA. In this study, we assessed the efficacy of PVA using an extracorporeal device to treat 2 ALF models in swine. MATERIALS AND METHODS: The 2 ALF swine models were carbon tetrachloride toxic ALF and subtotal hepatectomy using 8 animals per group. PVA was performed with an extracorporeal device that may be suitable for future clinical studies. Arterial blood was drawn from the iliac artery and delivered into the portal vein for a 6-hour treatment. We analyzed biochemical, blood gas, and histological parameters as well as 1-week survival rates. RESULTS: In both models, ALF was successfully achieved. Control group animals deteriorated biochemically, dropping their prothrombin times and increasing the liver enzymes. In contrast, treated animals improved with a survival rate of 75% at 7 days compared with 0% for the former group. CONCLUSIONS: PVA using an extracorporeal device was feasible and effective to treat both toxic and resective ALF in swine.     

Significant role of middle hepatic vein in remnant liver regeneration of right-lobe living donors

For adult patients with end-stage liver disease, living-donor liver transplantation (LDLT) of right-lobe grafts with or without the middle hepatic vein (MHV) has been increasingly used in recent years. We investigated the role of the MHV in donor remnant liver regeneration after right-lobe LDLT, which has not been described in previous studies. A total of eight living donors were included in this study of right-lobe LDLT. Four donors underwent right lobectomy (without MHV), and the remaining four underwent extended right lobectomy (with MHV). Regeneration of the donor remnant liver was assessed by volumetric computed tomography studies before and 90 days after LDLT. Comparison between the right-lobe and extended right-lobe donors did not show a clear-cut difference in the net increase of remnant liver volume at 3 months. However, the mean volume increase of the medial segment at the 90th postoperative day was 7% in the extended right-lobe donors and 61% in the right-lobe donors, showing a lower value in the remnant livers without MHV. The MHV plays a specific role in remnant liver regeneration of right-lobe living donors. We expect that this knowledge will contribute to securing a margin of safety in right-lobe LDLT.     

In situ liver transection with portal vein ligation for rapid growth of the future liver remnant in two‐stage liver resection

Background:

Portal vein embolization (PVE) has become a standard procedure to increase the future liver remnant (FLR) and enable curative resection of initially unresectable liver tumours. This study investigated the safety and feasibility of a new two‐stage liver resection technique that uses in situ liver transection (ISLT) and portal vein ligation before completion hepatectomy.

Methods:

A consecutive series of patients undergoing ISLT and extended right hepatectomy between 2009 and 2011 were compared with consecutive patients undergoing extended right hepatectomy after PVE. All patients had initially unresectable primary or secondary liver tumours, owing to an insufficient FLR (liver segments II/III).

Results:

Fifteen patients who had PVE and seven who underwent ISLT before extended right hepatectomy were evaluated. ISLT induced rapid growth of the FLR within 3 days, particularly after insufficient PVE, from a mean(s.d.) of 293(58) ml to 477(85) ml, corresponding to a volume increase of 63(29) per cent. All patients who had ISLT underwent completion extended right hepatectomy within 8 days (range 4–8 days).

Conclusion:

ISLT is an effective and reliable technique to induce rapid growth of the FLR, even in patients with insufficient volume increase after PVE. Copyright © 2012 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.     

Hepatic vein reconstruction for preserving remnant liver function

Hepatic malignancies often infiltrate to the major hepatic vein. Recently, we performed hepatic resection combined with hepatic vein reconstruction for preserving remnant liver function in three such patients. One patient had a saphenous vein graft. Postoperative liver function of the patients who underwent hepatic vein reconstruction was compared with those of eight patients who underwent hepatic resection of segments VII and VIII. The right hepatic vein in four of them was resected and in the remaining four was preserved by skeletalization using an ultrasonic aspirator. Although four patients with right hepatic vein resection showed severe lowering of liver function after surgery, the postoperative course of patients with preservation or reconstruction of the right hepatic vein maintained good liver function. Liver regeneration of three patients with hepatic vein reconstruction was good on computed tomography. Besides this report, to our knowledge, there is no other report of hepatic vein reconstruction for preserving the remnant liver function. Problems with hepatic resection combined with hepatic vein reconstruction are discussed. We conclude that hepatic vein reconstruction is one of the means for extending indication of the malignant tumor resection of the liver.     

门静脉动脉化对梗阻性黄疸时肝胆切除术后肝再生的影响

目的 观察慢性、梗阻性黄疸小型猪肝-胆切除术中限流性部分门静脉动脉化(PP-VA)对术后残肝再生能力的影响.方法 利用梗阻性黄疸小型猪模型,模拟进行联合半肝切除的肝门部胆管癌扩大根治性手术.实验分组:无黄疸对照组(A组)、门静脉动脉化组(B组)及非门静脉动脉化组(C组).对照观察根治术中应用限流性PPVA在术后30 d内对残肝再生的作用.结果 术后即刻及第30天门静脉PO2:B组高于C组[(47.33±2.43)比(35.38土4.06)mm Hg(1 mm Hg=0.133 kPa)、(48.50±4.44)比(35.55±2.55)mm Hg,P<0.01、P<0.01].肝细胞有丝分裂指数:术后第14及21天B组高于C组[(12.55±2.85)%比(6.85±2.10)%、(15.25±1.99)%比(11.88±1.15)%,P<0.05、P<0.05].术后第14、21天肝脏体积再生率B组分别高于C组[(24.56±6.15)%比(11.96±5.43)%、(70.63±9.83)比(44.92±7.42)%,P<0.05、P<0.01].结论 限流性PPVA可促进慢性梗黄小型猪肝-胆切除术后残肝再生,从而预防肝功能衰竭.     

肝硬化门静脉高压症患者肝移植术后门静脉血流动力学变化的临床研究

目的探讨肝硬化门静脉高压症患者肝移植术后早期门静脉系统血流动力学变化规律。方法应用彩色多普勒B超检测50例行原位肝移植术的肝硬化患者及24例正常对照的门静脉、脾静脉的直径、流速,脾脏的体积;应用压力传感器检测患者肝移植术中门静脉压力变化情况。结果肝移植术后门静脉直径变小,流速增高,流量增大,在观察期内持续高于正常对照。脾静脉流量增加不明显(g=3．21,P＞0．05)。门静脉压力由开腹时的(24．57±6．22)mm Hg降至关腹前的(16．81±5．03)mm Hg,仍稍高于正常值,降压效果明显,降幅达31．7%。术后静脉曲张情况明显改善。脾功能亢进在术后亦得到明显缓解,外周血中自细胞及血小板在短期内恢复正常(t=2．89,P＜0．05)。结论与术前相比,肝移植术后门静脉系统呈现高流速、高流量状态,短期内难以恢复。脾功能亢进得到明显缓解。门静脉压力在新肝植入2～4 h后较术前明显下降,接近正常水平。