A review of animal models for portal vein embolization

Background

Portal vein embolization (PVE) is a preoperative intervention to increase the future remnant liver (FRL) through regeneration of the non-embolized liver lobes. This review assesses all the relevant animal models of PVE available, to guide researchers who intend to study PVE.

Materials and methods

We performed a systematic literature search in Medline and Pubmed, from 1993–June 2013, using search headings “PVE” and “portal vein ligation”. Articles were included when meeting the selection criteria: experimental animal study on PVE or portal vein ligation and experiments described in 5 animals or more.

Results

Sixty-one articles were selected, describing six different animal models. Most articles reported experiments with rats, rabbits, and pigs. In rats, the increase in wet-weight ratio of the non-occluded liver or total liver weight is greatest in the first 7 d with values ranging from 75%–80.5% on day 7. The volume increase of FRL in the rabbit model is greatest in the first 7 d with values ranging from 33.6%–80% on day 7. In pigs, the largest gain in volume of the FRL was seen in the first 2 wk.

Conclusions

The choice of the model depends on the specific aim of the study. Evaluating the increase in liver volume and liver function after PVE, larger animals as the pig, rabbit, or the dog is useful because of the possibility to apply computed tomography volumetry. To evaluate mechanisms of regeneration after PVE, the rat model is useful, because of the variety of antibodies commercially available.     

Portal and mesenteric vein thrombosis after portal vein embolization in a patient with protein S deficiency

Portal vein embolization can be performed safely, and so far no major complications have been reported. We report an extremely rare complication of portal vein embolization, a case of portal and mesenteric thrombosis in a 65-year-old patient with protein S deficiency. Right portal vein embolization was carried out prior to extended right hepatectomy for advanced gallbladder carcinoma involving the hepatic hilus. Computed tomography 14 days after embolization revealed massive thrombosis of the portal and the superior mesenteric veins. A protein S deficiency was found by means of an extensive workup for hypercoagulable state. Portal vein embolization may have triggered a cascade of events that was expressed as portal and mesenteric vein thrombosis resulting from deficiency of protein S. It may be better to determine the concentrations of such coagulation regulators prior to portal vein embolization.     

肝脏肿瘤肝切除术前选择性门静脉栓塞的临床应用

目的 探讨选择性门静脉栓塞技术细节及其在残余肝容积不足患者肝切除术前应用的临床意义.方法 2008年1月至2012年7月,6例肝脏肿瘤因残余肝容积不足,二期肝切除术前行选择性门静脉栓塞术.结果 6例选择性门静脉栓塞术均成功.无手术并发症,栓塞对肝功能影响轻微.术前,6例残余肝容积平均(474.33 ±89.19) cm3,术后6周,平均(722.67±151.51) cm3,术前术后残余肝容积比较差异有统计学意义(t=-5.587,P=0.003).术前6例肝脏肿瘤负荷(瘤体总体积)平均(134±181) cm3,栓塞术后6周,肿瘤负荷平均为(270±346) cm3,栓塞前后肿瘤负荷比较差异无统计学意义(t=-1.64,P=0.16).5例二期肝切除术顺利.1例未行肝切除术.随访中位时间为37个月,4例存活(2例无瘤生存),1例死亡.结论 门静脉选择性栓塞是肝切除前增加残余肝容积的有效技术手段;经同侧(患侧)人路并选择弹簧圈作为栓塞材料简单易行、安全、有效.门静脉栓塞前,应以化疗或选择性肝动脉化疗栓塞等手段有效控制肿瘤生长.     

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。     

Arguments for a selective approach of preoperative portal vein embolization before major hepatic resection

Preoperative PVE can induce hypertrophy of the future liver remnant volume resulting in a decrease of surgical risk after major hepatic resection. However, the number of patients with normal liver at risk is small and there is no arguments for inducing hypertrophy before standard right hepatectomy. Therefore, in patients with normal liver PVE is indicated in patients in whom very extended liver resection or associated major gastro-intestinal surgery is planned. In patients with chronic liver disease and in those with injuried liver (chemotherapy, major steatosis, cholestasis), PVE is indicated before major liver resection.     

Present status and future perspectives of preoperative portal vein embolization

Background

Portal vein embolization (PVE) has been gaining increasing acceptance before major hepatectomy. This review presents the application, outcome, and recent developments of PVE.

Methods

After a systematic search of “portal vein embolization” in PubMed, we reviewed and retrieved articles written in English related to PVE. There were no other criteria for exclusion of published information pertaining to this topic.

Results

Hypertrophy of future liver remnants with PVE in patients with hepatobiliary malignancy results in fewer complications and shorter hospital stays after major hepatectomy, and add to the pool of candidates for surgical treatment. Some new techniques, such as sequential hepatic artery-portal vein embolization and PVE with stem cell administration, have showed a promising clinical future.

Conclusions

PVE has achieved significant improvement in the outcome of major hepatectomy, and has enlarged the candidate pool of liver resection as well. Future study is needed to identify the precise mechanism of liver regeneration after PVE.     

One or two-stage hepatectomy combined with portal vein embolization for initially nonresectable colorectal liver metastases

BACKGROUND: Portal vein embolization (PVE), proposed to induce contralateral hepatic hypertrophy before major hepatectomy, carries some negative side effects since growth rate of metastases in the future remnant liver (RL) can be more rapid than that of nontumoral liver parenchyma. Therefore, metastases in the RL should be ideally resected before PVE, and a major hepatectomy can then be performed after PVE in patients with multiple bilobar colorectal liver metastases (MBLM). The aim of this study was to assess feasibility and outcome in patients with initially unresectable colorectal liver metastases treated by a one- or two-stage hepatectomy procedure (TSHP) combined with PVE. PATIENTS AND METHODS: From December 1996 to December 1999, 180 patients with colorectal liver metastases underwent hepatectomy. During the same period, 18 were initially considered as unresectable. TSHP combined with PVE was attempted for 7 patients (group A) among those with MBLM, and a one-stage hepatectomy after PVE was attempted in another group of 11 patients (group B) among those with non-MBLM. RESULTS: Nonanatomical resections for left liver metastases were performed as a first stage without any complications in group A. A right hepatectomy (RH) was performed in 5 patients in group A (feasibility = 71%). In group B, 7 of the 11 patients underwent a RH or an extended RH after PVE (feasibility = 64%). Postoperative complications rate did not differ between group A and B. Mortality was nil. Three-year survival rate was 53% in group A and 100% in group B. CONCLUSIONS: These results suggest that one- or two-stage hepatectomy combined with PVE can be applied safely to selected patients initially considered as unresectable. Three-year survival was similar to that observed in patients with initially resectable liver metastases.     

Risk factors of posthepatectomy liver failure after portal vein embolization

Background/Purpose. Major hepatectomy has been successfully performed after portal vein embolization (PE). However, posthepatectomy liver failure following hyperbilirubinemia (HB) sometimes occurs even after PE. Our objective was to determine what factors affected post-hepatectomy HB and liver failure. Methods. Forty-two patients underwent PE before major hepatectomy or repeat hepatic resection after partial hepatectomy. Having a prognostic score over 40, they all belonged to a high-risk group. They were classified into two groups according to posthepatectomy levels of total bilirubin: normal group and HB group. The HB group was further divided into two subgroups: recovered subgroup and fatal subgroup. We investigated the differences between the two groups and the two subgroups. Results. Ten of 14 cases (71%) in the HB group were biliary tract disease with jaundice before PE. The indocyanine green retention rate (ICGR15) before PE, skeletonization of the hepatoduodenal ligament (HDL), and portal venous pressure after PE were significantly different between the two groups as shown by multivariate analysis. Postoperative complication was the only factor significantly different between the two subgroups by univariate analysis. Conclusions. When the patients underwent major hepatectomy combined with skeletonization of the HDL for biliary tract disease with jaundice, they were subject to posthepatectomy HB even after PE. If they had postoperative complications, fatal hepatic failure must have occurred.     

Outcome of patients with pre-existing portal vein thrombosis undergoing arterialization of the portal vein during liver transplantation

Arterialization of the portal vein is being propagated as a technical possibility in liver transplant recipients with pre-existing portal vein thrombosis. In our own small series, portal vein arterialization (PVA) was carried out in four patients undergoing orthotopic liver transplantation. In three of these cases, the portal vein was anastomosed to the aorta via an interposed iliac artery, and in one case, directly to the hepatic artery. After PVA, all transplants showed regular initial function. Two patients died postoperatively after 19 and 50 days, of intra-abdominal haemorrhage and liver necrosis with thrombosis of the portal vein, respectively. A further patient had previously developed fibrosis of the liver, which led to the death of the patient 11 months after PVA. In the remaining patient, chronic rejection requiring re-transplantation developed 24 months after PVA had been performed. These unfavourable results prompt the conclusion that PVA cannot be recommended as a standard clinical procedure.     

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目的 评估肝移植治疗肝细胞癌(HCC)合并门静脉癌栓(PVTT)病人的临床疗效，探讨其临床应用价值。方法 回顾性分析自1999年7月至2003年3月收治的24例施行肝移植的HCC合并PVTT病人(移植组)临床资料和生存情况。对照组分别选取同时期HCC合并PVTT行常规肝叶切除、门静脉癌栓取出术者(手术切除组，27例)和非手术治疗者(未手术组，59例)。结果 移植组手术死亡率(1个月内)为0；6个月、1年以及2年累积生存率分别为66.7％、29.5％和23.6％，均高于手术切除组的33.3％、22.2％和14.8％(P=0.0335)和非手术组的42.1％、24.4％和4.1％(P=0.0316)；移植组的6个月、1年和2年无瘤生存率分别为51.5％、23.2％和0；随访期间肝外转移或肝内复发的总发生率为66.7％。结论 现阶段HCC合并PVTT病人的肝移植治疗是一种有效的姑息性手术方式。     

高强度超声联合阿霉素治疗兔门静脉癌栓

目的探讨高强度超声(HI U)联合抗癌药物治疗兔门静脉癌栓的有效性和安全性。方法45只实验兔分为4组,VX2肿瘤种植于门静脉腔内5d,15只接受HI U治疗(HI U组);10只接受阿霉素治疗(ADM组);10只接受HI U ADM联合治疗(HI U ADM组);10只接受假照治疗(对照组)。从HI U组中随机取5只兔于治疗后7d测量门静脉压,处死后对其进行病理学及电镜检查,并观察记录各组兔生存时间。结果治疗后门静脉压无明显降低(P>0.05)。靶区组织发生凝固性坏死,靶区内门静脉无破裂及出血,HI U组、HI U ADM组较ADM组、对照组生存时间明显延长(P<0.05);ADM组、对照组两组间生存时间比较差异无统计学意义(P>0.05)。结论HI U联合抗癌药物能够较为安全有效地治疗兔门静脉癌栓。     

高强度超声联合阿霉素治疗兔门静脉癌栓

目的探讨高强度超声（HIU）联合抗癌药物治疗兔门静脉癌栓的有效性和安全性。方法45只实验兔分为4组，VX2肿瘤种植于门静脉腔内5d，15只接受HIU治疗（HIU组）；10只接受阿霉素治疗（ADM组）；10只接受HIU＋ADM联合治疗（HIU＋ADM组）；10只接受假照治疗（对照组）。从HIU组中随机取5只兔于治疗后7d测量门静脉压，处死后对其进行病理学及电镜检查，并观察记录各组兔生存时间。结果治疗后门静脉压无明显降低（P〉0．05）。靶区组织发生凝固性坏死，靶区内门静脉无破裂及出血，HIU组、HIU＋ADM组较ADM组、对照组生存时间明显延长（P〈0．05）；ADM组、对照组两组间生存时间比较差异无统计学意义（P〉0．05）。结论HIU联合抗癌药物能够较为安全有效地治疗兔门静脉癌栓。     

肝门部胆管癌术前门静脉栓塞的血流动力学与肝再生的关系

目的 研究肝门部胆管癌术前门静脉栓塞(PVE)前后血流动力学的变化,并分析其与非栓塞肝叶增生速度的关系.方法 回顾性分析2008年4月至2009年12月第二军医大学东方肝胆外科医院收治的21例肝门部胆管癌患者的临床资料.在手术治疗前进行钢圈PVE治疗,在该治疗前和治疗后第3、7、14天采用彩色多普勒超声对门静脉的血流动...     

肝移植中门静脉-内脏曲张静脉吻合在门静脉机化血栓患者的应用

目的:探讨门静脉-内脏曲张静脉吻合在门静脉机化血栓患者肝移植中的应用。方法:对门静脉和肠系膜上静脉均完全被机化血栓阻塞的7例患者实施肝移植,其中3例供体门静脉-曲张冠状静脉吻合;2例髂静脉搭桥供体门静脉和脾门旁曲张的静脉吻合;1例采用供体门静脉-胆总管前曲张静脉吻合;1例供体门静脉—曲张的胃网膜右静脉吻合。结果:7例手术全部成功。1例术后7d死于多脏器功能衰竭,但是门静脉血流一直通畅。1例术后6个月发现吻合口狭窄,术后9个月采用经皮肝穿刺门静脉支架置入治愈;其余患者分别随访12～22个月,门静脉血流均通畅,无狭窄或血栓形成,肝、肾功能正常。结论:肝移植中对门静脉和肠系膜上静脉均完全被机化血栓阻塞的患者,行供体门静脉-曲张内脏静脉吻合可取得良好疗效。     

腹腔镜选择性门静脉结扎术在二期肝癌肝切除术中的应用

目的 探讨腹腔镜选择性门静脉结扎术在二期肝癌肝切除术中的临床应用价值.方法 回顾性分析2009年3月至2012年2月四川省人民医院收治的23例无法一期手术切除的原发性肝癌患者的临床资料.先行腹腔镜选择性门静脉结扎术,术后3～4周,经CT检查了解各肝叶体积及预计肝切除体积的动态变化,评估肝癌可切除性后再行二期开腹肝癌肝切除术.组间比较采用方差分析,两两比较采用q检验(方差不齐数据行对数转换).结果 选择性门静脉结扎术:23例患者均行门静脉右支结扎,其中22例于腹腔镜下成功结扎门静脉右支(2例因暴露门静脉右支困难,同时行胆囊切除),1例患者因分离门静脉时出血,中转开腹行门静脉右支结扎.3例多发肿瘤患者行腹腔镜选择性门静脉结扎后1周加行TACE,其中2例行右半肝切除+健侧肝脏肿瘤RFA治疗.23例患者术后出现不同程度的肝区隐痛不适、低热、恶心、呕吐等非特异性反应,无腹腔出血、胆汁漏、肝脓肿等并发症发生;术后出现程度不同的肝功能损害,术后1周AST、ALT和TBil恢复至术前水平.术后右半肝体积逐渐缩小,术后3周患者右半肝体积为(590 ± 154) cm3,较术前(698±135)cm3明显缩小,术前与术后右半肝体积比较,差异有统计学意义(F=15.62,P＜0.05);术后3周左半肝体积为(408±149) cm3,较术前(331±68) cm3增生,术前与术后左半肝体积比较,差异有统计学意义(F=17.48,P＜0.05);预计肝切除体积占全肝体积百分比由术前的67％±15％缩小至术后3周时的60％±18％,术前与术后1、2、3周预计肝切除体积占全肝体积百分比比较,差异有统计学意义(F=12.35,P＜0.05).二期肝癌肝切除术:经CT检查评估后,23例患者中,2例因左半肝增生不明显、2例因术后(其中1例患者术前健侧肝脏发现转移癌)3周出现广泛肝内转移失去手术机会,2例失访,3例主动放弃二期肝癌肝切除术,14例在腹腔镜选择性门静脉结扎术后2～4周行二期肝癌肝切除术.手术切除率为60.9％(14/23).其中扩大右半肝切除2例、右半肝切除8例、不规则右半肝切除4例.二期肝癌肝切除术后患者恢复良好,无肝衰竭、严重腹腔积液、腹腔内感染等严重并发症发生,康复出院.结论 腹腔镜选择性门静脉结扎术治疗后预留剩余肝脏增生,使部分肝癌患者获得二期手术机会,且二期肝癌肝切除术后患者恢复良好.     

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).     

肝切除术前门静脉栓塞疗效的荟萃分析

目的 探讨肝切除术(右半肝、扩大半肝切除术)前应用门静脉栓塞(portal veinembolization,PVE)的临床价值.方法 通过电子检索Pubmed、Medline、Ovid数据库,对1986至2008年有关右半肝或扩大半肝切除术前行PVE的病例对照研究资料进行meta分析.结果 共纳入文献9篇,494例患者.荟萃分析结果 显示,PVE手术组较单纯手术组术后肝功能衰竭的发生率降低(P=0.02),但两者术后手术死亡的差异无统计学意义(P>0.05);亚组分析肝细胞癌和结直肠癌肝转移PVE手术组较单纯手术组1、3、5年生存率差异无统计学意义(P>0.05);1篇文献报道结肠癌肝转移发生率PVE手术组术后肝内复发转移发生较单纯手术组降低(P=0.001),而其他远处转移发生率相对增高(P=0.004).结论 术前行PVE能够有效降低术后肝功能衰竭的发生,但临床医师应当谨慎把握行术前PVE的指征.     

肝癌切除病人门静脉癌栓的分布状况

目的初步探讨分析肝癌切除病人门静脉癌栓的分布状况。方法对本组917例肝癌手术其门静脉癌栓的诊断,门静脉癌栓与原发肿瘤部位及肝癌病理的关系进行系统分析。结果本组资料中合并大体癌栓者139例(15.2%),仅病理镜下发现癌栓者540例(58.9%),无癌栓病人238例(25.9%)。合并大体癌栓139例中经术前各种影像学检查发现癌栓者92例(66.2%),至术中发现者32例(23.0%),至术后病理方发现者15例(10.8%)。肝癌位于左半肝者,大体癌栓的合并率为15.9%,位于右半肝者为13.8%,全肝多发肿瘤者为17.5%。各部位肿瘤合并大体癌栓侵犯同侧门静脉分支者占83.5%,大体癌栓同时侵犯左、右门静脉分支者占12.9%,侵犯病肝对侧门静脉分支者占3.6%。发生于右半肝的肝癌其大体癌栓侵犯门静脉主干者为26.7%,发生于左半肝者为8.6%,左、右半肝多发性肿瘤者为33.3%。肿瘤直径>5cm者大体PVTT合并率显著增高(P=0.003);包膜不完整者大体PVTT的合并率显著升高(P=0.000);组织分化低于III级的肝癌,其大体PVTT的合并率显著增高(P=0.009)。结论PVTT在肝癌中合并率高,肿瘤原发位置与大体PVTT侵犯的部位有显著相关性,右半肝和多发于全肝的肿瘤比左半肝肿瘤更易侵犯门静脉主干形成癌栓;大体PVTT的发生与肿瘤大小、包膜完整与否、组织分化程度有显著相关性,     

原发性肝癌合并门静脉癌栓的治疗策略

门静脉癌栓（portal vein tumor thrombus,PVTT）是原发性肝癌（hepatocellular carcinoma,HCC）的常见并发症,目前的治疗方法有外科手术切除、经肝动脉介入治疗、经门静脉介入治疗、经肝动脉和门静脉双途径介入治疗、放射治疗、消融治疗、肝移植、分子靶向治疗、综合治疗等,本文对上述各种治疗方法的近况进行了评价,以期进一步提高其治疗效果。