成人活体供者肝右叶联合脑死亡捐献者肝左外叶的双供肝活体肝移植治疗肝细胞癌的应用价值

目的探讨成人活体供者肝右叶联合脑死亡捐献者肝左外叶的双供肝活体肝移植治疗肝细胞癌的应用价值。方法采用回顾性描述性研究方法。收集2019年10月四川大学华西医院收治的1例行成人活体供者肝右叶联合脑死亡捐献者肝左外叶的双供肝活体肝移植受者的临床病理资料;男性肝细胞癌受者,年龄为46岁,体质量为66 kg,身高为171 cm,血型为A型Rh阳性。移植物1来自女性活体供者,年龄为23岁,体质量为50 kg,身高为150 cm,血型为A型Rh阳性。移植物2来自男性脑死亡捐献者,年龄为44岁,血型为A型Rh阳性。手术在3个手术间施行,2个手术间同时施行移植物1和移植物2的切取手术,第3个手术间施行受者肝脏游离,当移植物的体外拼接接近完成时,完整取出受者肝脏,并施行肝移植。观察指标:(1)活体供者及受者的手术及术后恢复情况。(2)受者病肝术后病理学检查情况。(3)随访情况。采用门诊方式进行随访,随访内容包括肝细胞癌复发监测、移植肝功能监测、免疫抑制剂监测调整、胆道血管并发症监测、排斥反应及药物不良反应等。受者需终生定期随访,最近一次随访时间为2019年12月4日。计数资料采用绝对数或百分比表示。结果(1)活体供者及受者的手术及术后恢复情况:活体供者手术时间为315 min,术中出血量约200 mL,术中输入自体回收血量约200 mL,术后第6天出院,无并发症发生。受者顺利完成改良背驼式肝移植。移植物1取自活体供者不含肝中静脉的肝右叶,质量410 g。移植物2取自脑死亡捐献者肝左外叶,质量400 g,拼接后的供者移植物质量与受者体质量比为1.2%。受者手术时间为815 min,无肝期时间为60 min,术中出血量约1500 mL,术中输血量为1800 mL。住院期间受者体温正常。术后第1天受者白细胞(WBC)和中性粒细胞百分比达到峰值(分别为17.15×109/L和91.7%),后逐渐降低,采用哌拉西林钠舒巴坦钠抗感染,术后第7天WBC和中性粒细胞百分比均降至正常范围(分别为7.90×109/L和70.9%),停用抗菌药物。住院期间,受者白蛋白(Alb)为31.0~41.4 g/L,受者总胆红素(TBil)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、凝血酶原时间、国际标准化比值肝功能指标均逐渐下降至正常范围,肌酐和肾小球滤过率肾功能指标均在正常范围。术后第10天受者全身状况良好,康复出院。(2)受者病肝术后病理学检查情况:①中分化肝细胞癌,肿瘤包膜欠完整,未侵及肝被膜,周围肝组织呈乙型病毒性肝炎后结节性肝硬化改变,肝门断端未见肿瘤累及;②慢性胆囊炎伴胆固醇沉积;③腹腔淋巴结1枚,呈反应性增生。免疫组织化学染色检测提示乙型肝炎表面抗原(10%细胞为阳性)、乙型肝炎核心抗原阴性。(3)随访情况:受者2019年11月19日复查肿瘤标志物,甲胎蛋白2.92μg/L、异常凝血酶原16 AU/L,结合腹部彩色多普勒超声检查的阴性结果提示肿瘤无复发。受者2019年12月3日复查肝功能:TBil 8.6μmol/L,ALT 23 IU/L,AST 28 IU/L,Alb 44.0 g/L;他克莫司血药浓度4.2μg/L,调整吗替麦考酚酯至250 mg 2次/d,其余治疗不变(他克莫司2 mg 1次/d,西罗莫司1 mg 1次/d);无症状、体征及检查结果提示胆道血管并发症、排斥反应及药物不良反应等。结论成人活体供者肝右叶联合脑死亡捐献者肝左外叶的双供肝活体肝移植安全、有效,可以作为治疗超出米兰标准肝细胞癌患者的次优方案。     

Pediatric living donor liver transplantation with large‐for‐size left lateral segment grafts

Usage of “large‐for‐size” left lateral segment (LLS) liver grafts in children with high graft to recipient weight ratio (GRWR) is controversial due to concerns about increased recipient complications. During the study period, 77 pediatric living donor liver transplantations (LDLTs) with LLS grafts were performed. We compared recipients with GRWR ≥2.5% (GR‐High = 50) vs GRWR <2.5% (GR‐Low = 27). Median age was higher in the GR‐Low group (40 vs 8 months, P> .0001). Graft (GR‐High: 98%, 98%, 98% vs GR‐Low: 96%, 93%, 93%) and patient (GR‐High: 98%, 98%, 98% vs GR‐Low: 100%, 96%, 96%) survival at 1, 3, and 5 years was similar between groups (P = NS). Overall complications were also similar (34% vs 30%; P = .8). Hepatic artery and portal vein thrombosis following transplantation was not different (P = NS). Delayed abdominal fascia closure was more common in GR‐High patients (17 vs 1; P = .002). Subgroup analysis comparing recipients with GRWR ≥4% (GR‐XL = 20) to GRWR <2.5% (GRWR‐Low = 27) revealed that delayed abdominal fascia closure was more common in the GR‐XL group, but postoperative complications and graft and patient survival were similar. We conclude that pediatric LDLT with large‐for‐size LLS grafts is associated with excellent clinical outcomes. There is an increased need for delayed abdominal closure with no compromise of long‐term outcomes. The use of high GRWR expands the donor pool and improves timely access to the benefits of transplantation without extra risks.     

Impact of graft thickness reduction of left lateral segment on outcomes following pediatric living donor liver transplantation

Reducing graft thickness is essential to prevent large‐for‐size graft problems in pediatric living donor liver transplantation (LDLT). However, long‐term outcomes of LDLT using reduced‐thickness left lateral segment (LLS) grafts are unclear. In 89 patients who underwent LDLT using reduced LLS grafts between 2005 and 2017, short‐term and long‐term outcomes were compared between a nonanatomically reduced LLS (NAR‐LLS) graft group and a reduced‐thickness LLS graft group. Estimated blood loss was lower and abdominal skin closure was less needed in the recipient operation in the reduced‐thickness LLS graft group. Postoperatively, portal vein (PV) flow was significantly decreased in the NAR‐LLS graft group, and there was shorter intensive care unit (ICU) stay and fewer postoperative complications, especially bacteremia, in the reduced‐thickness LLS graft group. Graft survival at 1 and 3 years after LDLT using reduced‐thickness LLS grafts was 95.2% and 92.4%, respectively, which was significantly better than for NAR‐LLS grafts. Multivariate analysis revealed that fulminant liver failure, hepatofugal PV flow before LDLT, and NAR‐LLS graft were associated with poor graft survival. In conclusion, LDLT using reduced‐thickness LLS grafts is a safe and feasible option with better short‐ and long‐term outcomes in comparison with NAR‐LLS grafts.     

Epidemiological study of survival after liver transplant from a living donor

The safety and success of solid organ transplants from living donors are critical issues in the overall decisional process; we are reporting here mortality outcome data collected from a single center. A cohort of 154 subjects who received a liver transplant from a living donor between 2001 and 2006 was retrospectively assembled at the University of Pittsburgh Transplant Center. The average follow up after transplant was 22.9 ± 18.5 months. During this time, 25 subjects died, contributing to an overall survival rate of 84%, similar to that reported by other studies on liver transplant from living donors. A multivariate analysis of the factors affecting survival did not identify any significant predictor of death. The study supports the safety of living liver transplants; larger collaborative studies that include detailed information on both recipients and donors, as well as the study of biological predictors of outcome are needed in order to continue monitoring the success of this approach.     

Simultaneous pancreas-kidney transplant from living related donor: a single-center experience

BACKGROUND: Simultaneous pancreas and kidney transplantation (SPK) from cadaveric donors has become a widely accepted therapeutic option for insulin-dependent uremic patients. In 1996 the first SPK from a live donor was performed. This procedure offers the advantage of a better immunologic match, reduced cold ischemia injury, and decreased waiting time. As such, it is an attractive alternative treatment for diabetic patients with end-stage nephropathy with an available living donor. METHODS: We performed six SPKs from living-related donors. There were four men and two women among the recipients; median age was 34 (range, 29-39) years. All donors were recipients' siblings with excellent HLA matching. Donors underwent standardized metabolic workup, anti-insulin and anti-islet antibody assays, and computed tomography of the abdomen. Both donors and recipients were treated with octreotide for 5 days perioperatively. After transplantation, the patients were maintained on tacrolimus-based immunosuppression, with the exception of one recipient of SPK from an identical twin, who received cyclosporine monotherapy. RESULTS: All the donors are doing well and have normal renal function and blood glucose levels. One-year patient, renal, and pancreatic graft survival rates were 100%, 100%, and 83%, respectively. Acute kidney rejection was documented in two patients, and both recovered completely after OKT3 therapy. No rejection of pancreatic graft has been documented. Except for one patient who lost the graft because of hemorrhagic pancreatitis, all recipients maintained serum glucose levels at less than 130 mg/dL without insulin therapy. No major surgical complications such as graft thrombosis, intra-abdominal infection, or abscess were reported. CONCLUSIONS: Living donor SPK can represent a successful alternative to cadaveric donor SPK. The procedure can be performed safely in the donor and with low morbidity in the recipient.     

Tape-guided living donor left hepatectomy

A procedure of tape-guided living donor left hepatectomy is described. A tape was placed along the anterior wall of the inferior vena cava for left liver with caudate lobe, and along Arantius' ligament for left liver without caudate lobe. The final step of liver transection was applied by dividing the liver parenchyma under tape guidance. This procedure contributed to safe and accurate anatomic procurement of left liver grafts in living donor hepatectomy.     

Early experience of a living donor kidney transplant program

OBJECTIVES: Laparoscopic nephrectomy has been shown to reduce the morbidity of live donor nephrectomy, but post-transplant kidney function and safety issues with the procedure are still of some concern. The review of our early experience could detect errors that should be avoided in the refining of the technique. METHODS: Our first sixty consecutive laparoscopic donor nephrectomies were analyzed retrospectively. RESULTS: There were conversions to open surgery (5%), all three in the first 18 cases. All donors were alive at 1 year with a glomerular filtration rate of 85+/-21 ml/min (78% of the basal). Patient and graft survival at 1 year was 100% and 95%, respectively. Creatinine nadir was achieved on post-transplant day 3 (creatinine, 176+/-122 micromol/l). Late renal function proved a continuous improvement until the 2-year follow-up (creatinine, 135+/-29 micromol/l). Renal function recovery was better in both recipient and donor when the donor was < or =50 years old, compared with older patients. Transplant complications that required reintervention included one ureteral fistula, one ureteral stenosis and one case of low renal flow that was re-vascularised. CONCLUSIONS: Technical surgical aspects such the use of Haemoloc clips in the clipping of the artery, the hand-assisted extraction of the kidney, a refined surgical technique during the transplant and avoidance of prolonged warm and cold ischemia, taken together with an adequate intraoperative hemodynamic management of the donor aid in avoiding life-threatening complications and achieving a good post-transplant renal function recovery.     

Necrotizing glomerulonephritis in a living donor kidney transplant recipient

The occurrence of a rapidly progressive necrotizing glomerulonephritis after kidney transplantation is exceptional and usually leads to graft failure. We describe a case of necrotizing glomerulonephritis that developed 5 months after renal transplantation in a patient suffering from prolonged bowel paralysis and sepsis. After reinforcement of corticosteroid therapy and introduction of cyclophosphamide, glomerulonephritis recovered. Cyclophosphamide was stopped after 2 months and replaced by azatioprine while prednisone was progressively reduced. Three years after transplantation the patient has a stable serum creatinine of 1.7 mg/dL and mild proteinuria. To the best of our knowledge this is the first case of recovery from a necrotizing glomerulonephritis in a renal transplant recipient.     

扩大供肾标准的亲属肾移植临床效果分析

目的 探讨扩大供肾标准的亲属肾移植临床效果.方法 回顾性分析2005年11月至2011年6月亲属活体肾移植274例的临床资料,按供者情况分为扩大供者标准(供者年龄≥60岁、肾脏解剖结构/功能异常)组(66例)和标准供者组(208例).扩大标准组供者年龄≥60岁36例,其中合并肾囊肿6例,合并肾结石1例;肾囊肿22例,囊肿直径4～40 mm;肾结石4例,结石直径3 ～～6 mm;术侧肾小球滤过率(GFR) ＜35 ml/min 4例.统计学比较两组受者术后3、7d,l、3、6、12个月血清SCr值、并发症发生率、急性排斥反应发生率、移植肾功能延迟恢复(DGF)发生率,1、3年人/肾存活率.结果 扩大标准组及标准供者组受者术后3、7d血清SCr值分别为(242.7±132.2)、( 185.6±148.4) μmol/L和(156.7±86.8)、( 122.2±136.8) μmol/L,两组受者第3天与第7天SCr值比较差异均有统计学意义(P＜0.05);但两组受者术后1、3、6、12个月血SCr、并发症发生率、急性排斥反应发生率、DGF发生率,1、3年人/肾存活率之间比较差异均无统计学意义(P＞0.05).结论 ≥60岁健康高龄、直径＜40 mm供肾囊肿仍可考虑作为亲属肾移植供者;低GFR应结合供者年龄、供受者体表面积比、供受者体质量比、可通过外科处理纠正等方面综合考虑;供肾结石者应慎重选择.     

Pharmacokinetics of tacrolimus in living donor liver transplant and deceased donor liver transplant recipients

INTRODUCTION: Hepatic dysfunction is an important determinant of the clearance of tacrolimus; however, the impact of reduced hepatic mass in living donor liver transplant (LDLT) patients on the drug exposure and clearance of tacrolimus is not known. AIM.: The aim of the present study is to compare the dosage, concentration and pharmacokinetics parameters of tacrolimus between LDLT and deceased donor liver transplant (DDLT) recipients. PATIENTS AND METHODS: Daily doses used and trough concentrations measured were compared in 12 LDLT and 12 DDLT patients. Multiple blood samples were taken over one dosing interval after oral tacrolimus administration, and pharmacokinetics differences were compared. RESULTS: The mean tacrolimus dosage in first 14 postoperative days was (0.06 mg/kg/day) for LDLT and (0.09 mg/kg/day) for DDLT (P=0.0001). Despite the lower doses used, mean trough concentration was significantly greater in LDLT as compared with DDLT (8.8+/-2.5 ng/mL vs. 6.79+/-1.5 ng/mL, respectively, P=0.013). On the day of the pharmacokinetic study, minimum Concentration (Cmin), 12-hr postdose concentration (Clast), and average concentration (Cavg) were significantly greater in LDLT as compared with DDLT (LDLT: 6.6+/-2.4 ng/mL, 7.2+/-1.8 ng/mL, 8.9+/-3.0 ng/mL; DDLT: 4.3+/-1.0 ng/mL, 4.9+/-1.6 ng/mL, 5.9+/-1.4 ng/mL, P=0.02, 0.04, and 0.02, respectively). Dose normalized AUC was 37.7% greater and clearance, 47.5% lower in LDLT as compared with DDLT. CONCLUSION: Although not statistically significant, the dose normalized AUC was 37.7% greater and clearance 47.5% lower in LDLT as compared with DDLT. An initial tacrolimus dose reduction of about 30-40% may be prudent in LDLT compared with DDLT recipients.     

肝左外叶切除“金标准”术式:腹腔镜肝左外叶切除术

<正>肝左外叶独特的解剖结构使得腹腔镜肝左外叶切除术(laparoscopic left lateral segment liver resection,LLLR)成为开展较早、应用较多的腹腔镜肝切除术(laparoscopic hepatectomy,LH)术式[1-5]。该术式在手术时     

Expanding living donor liver transplantation: Report of first US living donor liver transplant chain

Living donor liver transplantation (LDLT) enjoys widespread use in Asia, but remains limited to a handful of centers in North America and comprises only 5% of liver transplants performed in the United States. In contrast, living donor kidney transplantation is used frequently in the United States, and has evolved to commonly include paired exchanges, particularly for ABO-incompatible pairs. Liver paired exchange (LPE) has been utilized in Asia, and was recently reported in Canada; here we report the first LPE performed in the United States, and the first LPE to be performed on consecutive days. The LPE performed at our institution was initiated by a nondirected donor who enabled the exchange for an ABO-incompatible pair, and the final recipient was selected from our deceased donor waitlist. The exchange was performed over the course of 2 consecutive days, and relied on the use and compliance of a bridge donor. Here, we show that LPE is feasible at centers with significant LDLT experience and affords an opportunity to expand LDLT in cases of ABO incompatibility or when nondirected donors arise. To our knowledge, this represents the first exchange of its kind in the United States.     

Shipping living donor kidneys and transplant recipient outcomes

Kidney paired donation (KPD) is an important tool to facilitate living donor kidney transplantation (LDKT). Concerns remain over prolonged cold ischemia times (CIT) associated with shipping kidneys long distances through KPD. We examined the association between CIT and delayed graft function (DGF), allograft survival, and patient survival for 1267 shipped and 205 nonshipped/internal KPD LDKTs facilitated by the National Kidney Registry in the United States from 2008 to 2015, compared to 4800 unrelated, nonshipped, non‐KPD LDKTs. Shipped KPD recipients had a median CIT of 9.3 hours (range = 0.25‐23.9 hours), compared to 1.0 hour for internal KPD transplants and 0.93 hours for non‐KPD LDKTs. Each hour of CIT was associated with a 5% increased odds of DGF (adjusted odds ratio: 1.05, 95% confidence interval [CI], 1.02‐1.09, P < .01). However, there was not a significant association between CIT and all‐cause graft failure (adjusted hazard ratio [aHR]: 1.01, 95% CI: 0.98‐1.04, P = .4), death‐censored graft failure ( [aHR]: 1.02, 95% CI, 0.98‐1.06, P = .4), or mortality (aHR 1.00, 95% CI, 0.96‐1.04, P > .9). This study of KPD‐facilitated LDKTs found no evidence that long CIT is a concern for reduced graft or patient survival. Studies with longer follow‐up are needed to refine our understanding of the safety of shipping donor kidneys through KPD.