Development and validation of a nomogram based on perioperative risk factors for the prediction of early thrombotic complications following pediatric liver transplantation

To the Editor:Despite dramatic improvements in the prognosis of pediatric liver transplantation(LT),postoperative complications are still a leading cause of death in grafts and patients.Child recipients were shown to have a higher risk of thrombotic complications than in adult recipients,due to differences in etiology,narrowed hepatic vessels due to hypoplasia,more meticulous surgical techniques,and other factors.[1]Thrombotic complications include hepatic artery thrombosis(HAT).

Chinese clinical practice guidelines for pediatric split liver transplantation

Liver transplantation is an effective treatment for end-stage liver disease in children,and its clinical efficacy has been validated.Split liver transplantation(SLT)can effectively expand the donor liver pool for children.SLT for children has unique clinical characteristics and principles.Establishing technical operation specifications for pediatric SLT plays a significant role in improving clinical efficacy.In this paper,clinical practice guidelines on pediatric SLT were established in the aspect of donor and donor liver evaluation,donor-recipient matching,and ductal segmentation and reconstruction of donor liver,aiming to standardize the technical process,optimize surgical operational details,minimize the risk of complications of SLT for children,further promoting the rapid development of pediatric SLT in China.

Split liver transplantation in China:Past,present,and future

Split liver transplantation(SLT)is a procedure where an intact donor liver is splitted into two anatomically and functionally independent grafts,which are transplanted to two recipients.SLT can effectively expand the source of donor liver,and has become the predominant surgical solution to the shortage of donor livers after years of exploration and refinement.

合并高钠血症供肝在劈离式肝移植中的应用

目的探讨不同程度高钠血症供肝在劈离式肝移植(SLT)中应用的安全性和疗效。方法回顾性分析2017年9月至2022年1月在中山大学附属第三医院行SLT的连续122例供受者临床资料。供受者或(和)家属均签署知情同意书,符合医学伦理学规定。供者均为公民逝世后器官捐献,其中男97例,女25例;年龄4.6~56.8岁,中位年龄27.3岁。受者中,男85例,女37例;年龄0.2~82.8岁,中位年龄8.0岁。供者和受者经过严格筛选和匹配,选择循环稳定的供者,尽可能缩短冷缺血时间(CIT)≤8 h,供肝尽可能选取质地柔软、无或轻微脂肪变(<10%),并优化供肝灌注流程。根据供者血钠浓度将受者分为高钠血症组(160 mmol/L≤血清钠浓度<170 mmol/L,22例)和对照组(血清钠浓度<160 mmol/L,100例)。两组受者CIT、术中出血量比较采用秩和检验;术后7 d早期移植物功能障碍发生率、术后30 d死亡比较采用χ2检验;术后90 d生存情况分析采用Kaplan-Meier法和Log-rank检验。结果高钠血症组CIT和术中出血量中位数分别为445(360,514)min、700(300,1500)ml,对照组相应为450(360,510)min、500(200,1200)ml,差异无统计学意义(Z=-0.182,0.448;P>0.05)。两组受者术后7 d早期移植物功能障碍发生率分别为36%(8/22)、40%(40/100),术后30 d死亡率分别为5%(1/22)、6%(6/100),差异无统计学意义(χ2=0.100,0.071;P>0.05);两组受者术后90 d累积生存率分别为90.9%、93.0%,两组术后生存率比较差异无统计学意义(χ2=0.014,P>0.05)。结论供者血清钠浓度<160 mmol/L的供肝可用于劈离;当160 mmol/L≤血清钠浓度<170 mmol/L时,通过更加严格的脂肪肝评估、CIT控制和优化供肝灌注流程,亦可谨慎安全地实施SLT。

儿童劈离式肝移植术后肝动脉血栓形成的预防策略

目的探讨儿童劈离式肝移植(SLT)术后肝动脉血栓形成(HAT)的预防策略。方法回顾性分析2014年7月至2022年1月中山大学附属第三医院接受SLT的连续88例儿童受者临床资料。受者家属均签署知情同意书,符合医学伦理学规定。其中受者男56例,女32例;年龄2~208个月,中位年龄9个月。供肝类型包括右三叶供肝11例,右半肝供肝5例,左半肝供肝9例,左外叶供肝63例。供受者动脉在3.5倍手术放大镜下用8-0血管缝线间断端端吻合,尽量吻合所有动脉分支,吻合完成后、关腹前、关腹后常规使用彩超和血流仪监测血管血流情况,术后按肝素钠桥接华法林方案抗凝。结果2例患儿术后第1天发生HAT,HAT发生率2%(2/88),其供肝类型分别为儿童右三叶供肝和儿童左外叶供肝,均立即予介入下溶栓及肝动脉支架置入。1例支架置入后肝动脉复通,规律随访48个月,无血管、胆道并发症;另1例术后第2天因多器官功能衰竭死亡。结论合理的供受者动脉匹配、手术放大镜下间断吻合所有动脉分支、标准化抗凝方案和规范化围手术期血流监测等综合策略可有效预防儿童SLT受者术后发生HAT。

Expert consensus on split-liver transplantation

With the dawn of organ donation after a citizen's death in China,the use of split-liver transplantation(SLT)can effectively increase the source of donor liver,reduce the waiting time for organ transplantation in patients,and particularly solve the problem of organ shortage in children.In recent years,many transplantation centers have been performing SLT to varying degrees and efficacy.At the current stage,the experiences of countries with advanced transplantation techniques should be used to establish an SLT consensus that is suitable for China to further increase the ratio and efficacy of SLT.In this paper,we combined expert experiences to generate an SLT expert consensus that included donor and donor liver evaluation,recipient selection criteria,donor and recipient matching,selection of splitting form and tools,blood vessels and bile ducts dissection and allocation,perioperative management of SLT,and organ allocation.

Camrelizumab(SHR-1210)treatment for recurrent hepatocellular carcinoma after liver transplant:A report of two cases

Immune checkpoint inhibitors are generally contraindicated for post-transplant patients.However,we report two patients with metastatic hepatocellular carcinoma(HCC)treated with camrelizumab(SHR-1210),an anti-programmed cell death 1(PD-1)agent,after liver transplant.Before undergoing immunotherapy,both patients underwent liver allograft biopsy and obtained negative PD-L1 expression in tumor and liver graft specimens by immunohistochemistry.Then,camrelizumab(200 mg)was administered once every 3 weeks.During immunotherapy,the targeted therapy was continued,and the immunosuppression regimen was adjusted to a low-dose level.No graft rejection or other severe adverse reactions were observed.The disease remained stable(SD,mRECIST)for 3 months in one patient and 10 months in the other.Therefore,camrelizumab may have safety and potential benefits in advanced HCC after liver transplant.

A digital microfluidic system with 3D microstructures for single-cell culture

Despite the precise controllability of droplet samples in digital microfluidic(DMF)systems,their capability in isolating single cells for long-time culture is still limited:typically,only a few cells can be captured on an electrode.Although fabricating small-sized hydrophilic micropatches on an electrode aids single-cell capture,the actuation voltage for droplet transportation has to be significantly raised,resulting in a shorter lifetime for the DMF chip and a larger risk of damaging the cells.In this work,a DMF system with 3D microstructures engineered on-chip is proposed to form semi-closed micro-wells for efficient single-cell isolation and long-time culture.Our optimum results showed that approximately 20%of the micro-wells over a 30×30 array were occupied by isolated single cells.In addition,low-evaporation-temperature oil and surfactant aided the system in achieving a low droplet actuation voltage of 36V,which was 4 times lower than the typical 150 V,minimizing the potential damage to the cells in the droplets and to the DMF chip.To exemplify the technological advances,drug sensitivity tests were run in our DMF system to investigate the cell response of breast cancer cells(MDA-MB-231)and breast normal cells(MCF-10A)to a widely used chemotherapeutic drug,Cisplatin(Cis).The results on-chip were consistent with those screened in conventional 96-well plates.This novel,simple and robust single-cell trapping method has great potential in biological research at the single cell level.

Mesenchymal stem cells for treatment of steroid-resistant acute rejection after liver transplantation

A patient with steroid-resistant acute rejection 50 days after ABO-compatible orthotopic liver transplantation(LT)received regular infusion of allogeneic mesenchymal stem cells(MSCs)after three sessions of steroid pulse therapy which failed to control the pathogenetic condition as shown by biopsy.Liver function improved gradually after intravenous injection of MSCs once weekly for 10 weeks(as confirmed by biopsy)and remained stable under administration of conventional immunosuppressive agents.There was no evidence of neoplasms 5 years after treatment.MSCs infusion appears to successfully reverse resistance to immunosuppressive agents and may be a useful treatment for post-liver transplant steroid-resistant rejection.