大鼠30%小体积肝移植模型两种切肝方法的比较

目的探讨建立理想的成功率较高的大鼠30%小体积肝移植模型的可靠方法。方法采用改良＂二袖套法＂非动脉化法建立大鼠30%小体积肝移植模型。实验组分为两组：A组,右叶＋三角叶＋尾状叶做供肝的30%小体积肝移植组,共40例;B组,中叶做供肝的30%小体积肝移植组,共40例。观察两组术后并发症和术后3 d生存率。结果 A、B组切肝时间分别为（11±3）、（14±3）min,P〈0.01;术后发生肝后下腔静脉狭窄分别有2例、8例,P〈0.05;术后3 d生存率分别为53%（21/40）、40%（16/40）,P〉0.05;断面出血、胆漏和感染的发生率两组无明显差异。结论通过技术改良,可以以右叶＋三角叶＋尾状叶为供肝建立稳定的大鼠30%小体积肝移植模型。     

重建肝动脉大鼠肝移植模型的建立

目前最流行的大鼠原位肝移植方法是“二袖套”法,即肝上下腔静脉（SVC）缝合加肝下下腔静脉（IVC）及门静脉（PV）袖套吻合。上述方法虽不重建肝动脉,但术后大鼠均可获得存活。但研究发现,重建大鼠肝动脉则可显著降低术后胆道并发症,提高术后长期生存率。为此,我们在改进“二袖套”法大鼠肝移植基础上建立了重建肝动脉大鼠肝移植模型,旨在下一步进行肝移植方面的基础研究。     

活体肝移植后小肝综合征的防治

活体肝移植是治疗终末期肝病最有效的手段,但小肝综合征是成人活体肝移植术后一种发生率和病死率都较高的临床并发症,是制约成人间活体肝移植的主要原因之一.目前,如何有效防治小肝综合征已成为肝移植领域的研究热点.本篇就活体肝移植后小肝综合征的病理生理、危险因素及防治策略的最新进展作一简要综述.     

2023年国际肝移植学会活体肝移植“小肝综合征”预防指南

国际肝移植学会近期在Transplantation上发表了预防活体肝移植中的“小肝综合征”指南。这份指南为活体肝移植术中小肝综合征的预防提供了数据为支撑的临床路径,对小肝综合征预防的各种因素,包括供体和受体的选择、术中和术后管理等进行了广泛探讨。     

肠屏障和肝屏障损伤及保护在减体积肝移植术后小肝综合征中的研究进展

肠屏障可以抵抗病原体的侵袭,阻止有害物质进入血液循环,从而保持机体内环境的稳定.肝屏障对于维护肝脏正常功能有重要意义,其可阻止内毒素、病毒等进入肝脏损伤肝细胞.肠屏障和肝屏障是减体积肝移植术后最易受到损伤的2个结构,其损伤的原因与术后"小肝综合征"的发生有关."小肝综合征"的发病机制与肝移植术后门静脉高压、门静脉过度灌注等有关.如何有效地控制"小肝综合征"的发生,保护术后的肠屏障和肝屏障,是维持肠道和肝脏功能的关键点.本文主要阐述肠屏障和肝屏障的概念,分析其功能和结构破坏的原因以及相应的保护措施.     

白细胞介素-10与减体积大鼠肝移植后肝再生的关系

目的 探讨白细胞介素-10(IL-10)与减体积大鼠肝移植术后移植肝再生的关系。方法 建立减体积大鼠肝移植模型,实验分为:肝切除组、全肝移植组和减体积肝移植组,分别于术后1、2、4、7d取肝组织,免疫组织化学检测各组IL-10的表达,流式细胞仪检测移植肝的增殖活性。结果 肝切除组、全肝移植组和减体积肝移植组肝细胞增生活跃,术后4d增殖高峰分别为26.3±0.9、35.8±2.2、32.4±1.8。IL-10与移植后肝再生呈负相关(r=-0.58,P<0.01)。结论 减体积肝移植和全肝移植术后肝脏具有同样的增殖活性,但增殖峰值较肝切除延迟。IL-10对移植肝肝再生具有明显的调控作用,同时受免疫系统产生的其它细胞因子和激素的影响。     

原位肝移植治疗肝小静脉闭塞病1例

1病例资料患者,男,57岁,因腹胀、腹痛1个月余入院。1个月前,患者无明显诱因出现腹胀、右上腹痛,发现肝脏肿大和腹水到眉山市人民医院治疗。有饮酒史30年,每日摄入乙醇约120 g。查体：一般情况差,皮肤巩膜无黄染,可见肝掌,未见蜘蛛痣,心肺无异常,腹膨隆,腹软,中上腹轻压痛,无反跳痛及肌紧张,     

肝门部胆管癌行肝移植术7例

目的:报道7例不可手术切除的肝门部胆管癌患者行肝移植术,结合文献对其临床预后因素、临床结果进行分析.方法:回顾性调查研究分析2000-03/2010-12中国人民解放军海军总医院7例肝门部胆管癌行肝移植患者的临床资料,分析总结其临床病理特征、术后生存时间、肿瘤复发以及预后因素.结果:7例患者术前评估均不能达到根治性切除,均行肝移植术,术后病理诊断明确,无围手术期死亡,淋巴结转移者为57.1%(4/7),2例术前CA19-9100 KU/L.随访时间为7-108 mo,7例均死亡,肿瘤特异性死亡者5例,其中淋巴结阴性者[国际抗癌联盟(Union for International Cancer Control,UICC)分期均为2期]生存时间分别为108、37 mo,淋巴结阳性者(UICC分期,2例3b期,1例4a期)则分别为11、26、7 mo;而肿瘤非特异性死亡者2例,生存时间分别为18、34 mo.结论:对于不能外科手术切除且无淋巴结转移的肝门部胆管癌患者行肝移植术是一种有效的治疗手段.     

苦参碱对大鼠小体积肝移植缺血再灌注损伤的保护作用

目的: 探讨苦参碱对大鼠小体积肝移植缺血再灌注损伤的保护作用及机制.方法:采用大鼠30%小体积肝移植模型, ♂SD大鼠322只随机分为假手术组、小体积肝移植对照组和高、低剂量苦参碱治疗组(60、40 mg/kg). 观察术后1 wk生存率, 检测移植术2h、4 h、1 d、2 d、3d、7 d后ALT、AST及LDH值. 光镜及电镜下评估移植肝病理形态学改变, ELISA法检测肝脏IL-6, TNF-α表达.结果: 与对照组比较, 苦参碱高、低剂量治疗组术后1 wk生存率显著增加(80%, 70% vs 50%, 均P<0.05), 术后2h、4h、1d ALT、AST及LDH明显降低(P<0.01). 苦参碱治疗组中肝细胞和肝窦内皮细胞凋亡减少、细胞形态明显改善, 苦参碱治疗组术后2 h、4 h、1 d肝脏组织中IL-6, TNF-α水平明显降低(P<0.01). 结论:苦参碱可减轻肝细胞及肝窦内皮细胞的损伤, 改善小体积肝移植术后缺血再灌注损伤, 其机制可能与苦参碱抑制肝移植术后IL-6、TNF-α等炎症因子的释放有关.     

Outcome of patients undergoing right lobe living donor liver transplantation with small-for-size grafts

AIM:To investigate the outcome of living donor liver transplantation(LDLT)recipients transplanted with small-for-size grafts(SFSGs).METHODS:Between November 2001 and December2010,196 patients underwent LDLT with right lobe liver grafts at our center.Recipients were divided into 2 treatment groups:group A with an actuarial graft-to-recipient weight ratio(aGRWR)<0.8%(n=45)and group B with an aGRWR≥0.8%(n=151).We evaluated serum liver function markers within 4 wk after transplantation.We also retrospectively evaluated the outcomes of these patients for potential effects related to the recipients,the donors and the transplantation procedures based upon a review of their medical records.RESULTS:Small-for-size syndrome(SFSS)developed in 7 of 45 patients(15.56%)in group A and 9 of 151patients(5.96%)in group B(P=0.080).The levels of alanine aminotransferase and aspartate aminotransferase in group A were higher than those in group B during early period after transplantation,albeit not significantly.The cumulative 1-,3-and 5-year liver graft survival rates were 82.22%,71.11%and 71.11%for group A and 81.46%,76.82%,and 75.50%for group B patients,respectively(P=0.623).However,univariate analysis of risk factors associated with graft survival in group A demonstrated that the occurrence of SFSS after LDLT was the only significant risk factor affecting graft survival(P<0.001).Furthermore,multivariate analysis of our data did not identify any additional significant risk factors accounting for poor graft survival.CONCLUSION:Our study suggests that LDLT recipients with an aGRWR<0.8%may have liver graft outcomes comparable to those who received larger size grafts.Further studies are required to ascertain the safety of using SFSGs.     

Small-for-size syndrome in adult-to-adult living-related liver transplantation

Small-for-size syndrome (SFSS) in adult-to-adult living-related donor liver transplantation (LRLT) remains the greatest limiting factor for the expansion of segmental liver transplantation from either cadaveric or living donors. Portal hyperperfusion, venous pathology, and the arterial buffer response signif icantly contribute to clinical and histopathological manifestations of SFSS. Here, we review the technical aspects of surgical and radiological procedures developed to treat SFSS in LRLT, along with the...     

Impact of small-for-size liver grafts on medium-term and long-term graft survival in living donor liver transplantation: A meta-analysis

BACKGROUND Small-for-size grafts(SFSGs) in living donor liver transplantation(LDLT) could optimize donor postoperative outcomes and also expand the potential donor pool. Evidence on whether SFSGs would affect medium-term and long-term recipient graft survival is lacking.AIM To evaluate the impact of small-for-size liver grafts on medium-term and longterm graft survival in adult to adult LDLT.METHODS A systematic review and meta-analysis were performed by searching eligible studies published before January 24, 2019 on Pub Med, EMBASE, and Web of Science databases. The primary outcomes were 3-year and 5-year graft survival.Incidence of small-for-size syndrome and short term mortality were also extracted.RESULTS This meta-analysis is reported according to the guidelines of the PRISMA 2009 Statement. Seven retrospective observational studies with a total of 1821 LDLT recipients were included in the meta-analysis. SFSG is associated with significantly poorer medium-term graft survival. The pooled odds ratio for 3-year graft survival was 1.58 [95% confidence interval 1.10-2.29, P = 0.014]. On the other hand, pooled results of the studies showed that SFSG had no significant discriminatory effect on 5-year graft survival with an odds ratio of 1.31(95%confidence interval 0.87-1.97, P = 0.199). Furthermore, incidence of small-for-size syndrome detected in recipients of SFSG ranged from 0-11.4% in the included studies.CONCLUSION SFSG is associated with inferior medium-term but not long-term graft survival.Comparable long-term graft survival based on liver graft size shows that smaller grafts could be accepted for LDLT with appropriate flow modulatory measures.Close follow-up for graft function is warranted within 3 years after liver transplantation.     

建立大鼠部分肝移植动脉化模型的技术改进

目的:建立大鼠部分肝移植动脉化模型的技术改进.方法:采用改良二袖套法建立大鼠部分肝移植模型,并进行供体的腹腔动脉与受体的右肾动脉端端吻合.供肝予以切除尾叶、肝左叶及肝中叶的左半.结果:48例正式实验中,有5例于术中死亡,供肝热缺血时间为1.0±0.5 min.大鼠部分肝移植术后1 wk存活率为85.4%.结论:通过技术改进,提高了模型建立的稳定性.     

Excessive portal flow causes graft failure in extremely small-for-size liver transplantation in pigs

AIM: To evaluate the effects of a portocaval shunt on the decrease of excessive portal flow for the prevention of sinusoidal microcirculatory injury in extremely small-for-size liver transplantation in pigs. METHODS: The right lateral lobe of pigs, i.e. the 25% of the liver, was transplanted orthotopically. The pigs were divided into two groups: graft without portocaval shunt (n = 11) and graft with portocaval shunt (n = 11). Survival rate, portal flow, hepatic arterial flow, and histological findings were investigated. RESULTS: In the group without portocaval shunt, all pigs except one died of liver dysfunction within 24 h after transplantation. In the group with portocaval shunt, eight pigs survived for more than 4 d. The portal flow volumes before and after transplantation in the group without portocaval shunt were 118.2±26.9 mL/min/100 g liver tissue and 270.5±72.9 mL/min/100 g liver tissue, respectively. On the other hand, in the group with portocaval shunt, those volumes were 124.2±27.8 mL/ min/100 g liver tissue and 42.7±32.3 mL/min/100 g liver tissue, respectively (P<0.01). As for histological findings in the group without portocaval shunt, destruction of the sinusoidal lining and bleeding in the peri-portal areas were observed after reperfusion, but these findings were not recognized in the group with portocaval shunt. CONCLUSION: These results suggest that excessive portal flow is attributed to post transplant liver dysfunction after extreme small-for-size liver transplantation caused by sinusoidal microcirculatory injury.     

Tacrolimus dosage requirements in living donor liver transplant recipients with small-for-size grafts

AIM： To investigate the tacrolimus dosage requirements and blood concentrations in adult-to-adult right lobe living donor liver transplantation （AALDLT） recipients with small-for-size （SFS） grafts. METHODS： During January 2007 and October 2008, a total of 54 cases of AALDLT with an observation period of 6 mo were enrolled in this study. The 54 patients were divided into two groups according to graftrecipient body weight ratio （GRBW）： SFS grafts group （Group S, GRBW 〈 0.8%, n = 8） and non-SFS grafts group （Group N, GRBW ≥ 0.8%, n = 46）. Tacrolimus 12-hour blood levels and doses were recorded during weeks 1, 2, 3 and 4 and months 2, 3, 4, 5 and 6 in group S and group N. Meanwhile, acute rejection rates, liver and renal function test results, and the number of potentially interacting medications were determined at each interval in the two groups. A comparison of tacrolimus dosage requirements and blood levels were made weekly in the first month post-surgery, and monthly from months 2 to 6. RESULTS： There were no differences in the demo-graphic characteristics, acute rejection rates, liver and renal function test results, or the number of potentially interacting medications administered between the two groups. The tacrolimus dosage requirements in group S were significantly lower than group N at 2 wk （2.8 ± 0.4 mg/d vs 3.6 ± 0.7 mg/d, P = 0.006）, 3 wk （2.9± 0.7 mg/d vs 3.9±0.8 rag/d, P = 0.008）, 4 wk （2.9 ± 0.8 mg/d vs 3.9 ± 1.0 mg/d, P = 0.023） and 2 mo （2.8 ±0.7 mg/d vs 3.8±1.1 mg/d, P = 0.033）. Tacrolimus 12-h trough concentrations were similar between the two groups at all times except for 2 wk post-transplantation, when the concentrations were significantly greater in group S recipients than in group N recipients （11.3 ± 4.8 ng/mL vs 7.0 ± 3.8 ng/mL, P = 0.026）. CONCLUSION： SFS grafts recipients have significantly decreased tacrolimus dosage requirements compared with non-SFS grafts recipients in AALDLT during the first 2 mo post-surgery.     

Laparoscopic liver resection facilitates salvage liver transplantation for hepatocellular carcinoma

Background/Purpose

In patients with hepatocellular carcinoma (HCC), a previous liver resection (LR) may compromise subsequent liver transplantation (LT) by creating adhesions and increasing surgical difficulty. Initial laparoscopic LR (LLR) may reduce such technical consequences, but its effect on subsequent LT has not been reported. We report the operative results of LT after laparoscopic or open liver resection (OLR).

Methods

Twenty-four LT were performed, 12 following prior LLR and 12 following prior OLR. The LT was performed using preservation of the inferior vein cava. Indication for the LT was recurrent HCC in 19 cases (salvage LT), while five patients were listed for LT and underwent resection as a neoadjuvant procedure (bridge resection).

Results

In the LLR group, absence of adhesions was associated with straightforward access to the liver in all cases. In the OLR group, 11 patients required long and hemorrhagic dissection. Median durations of the hepatectomy phase and whole LT were 2.5 and 6.2 h, and 4.5 and 8.3 h in the LLR and OLR groups, respectively (P < 0.05). Median blood loss was 1200 ml and 2300 ml in the LLR and OLR groups, respectively (P < 0.05). Median transfusions of hepatectomy phase and whole LT were 0 and 3 U, and 2 and 6 U, respectively (P < 0.05). There were no postoperative deaths.

Conclusions

In our study, LLR facilitated the LT procedure as compared with OLR in terms of reduced operative time, blood loss and transfusion requirements. We conclude that LLR should be preferred over OLR when feasible in potential transplant candidates.     

Expression of iNOS in early injury in a rat model of small-for-size liver transplantation

BACKGROUND:Living donor liver transplantation has been widely accepted as the treatment of choice for end-stage liver disease.Large amounts of nitric oxide generated by inducible nitric oxide synthase(iNOS)have been shown to play an important role in many inflammatory and immune reactions,but expression of iNOS in small-for-size liver transplantation is unknown.The aims of this study were to determine the time course of iNOS mRNA and protein as well as the redox state of liver biopsies in a rat model of sma...     

Liver function impairment in liver transplantation and after extended hepatectomy

Extended hepatectomy,or liver transplantation of reduced-size graft,can lead to a pattern of clinical manifestations,namely"post-hepatectomy liver failure"and"small-for-size syndrome"respectively,that can range from mild cholestasis to irreversible organ non-function and death of the patient.Many mechanisms are involved in their occurrence but in the recent past,high portal blood flow through a relatively small liver vascular bed has taken a central role.Therefore,several techniques of inflow modulation have been attempted in cases of portal hyperperfusion first in liver transplantation,such as portocaval shunt,mesocaval shunt,splenorenal shunt,splenectomy or ligation of the splenic artery.However,high portal flow is not the only factor responsible,and before major liver resections,preoperative assessment of the residual liver function is necessary.Techniques such as portal vein embolization or portal vein ligation can be adopted to increase the future liver volume,preventing posthepatectomy liver failure.More recently,a new surgical procedure,that combines in situ splitting of the liver and portal vein ligation,has gradually come to light,inducing remarkable hypertrophy of the healthy liver in just a few days.Further studies are needed to confirm this hypothesis and overcome one of the biggest issues in the field of liver surgery.