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Unique multidisciplinary approach in living donor liver transplantation to achieve total physiological revascularization in a patient with complete occlusion of portal vein system with combined chronic and subacute thrombosis. 在活体肝移植手术中采用独特的多学科方法,为一名门静脉系统完全闭塞并合并慢性和亚急性血栓形成的患者实现完全生理性血管再通。
IF 8.9 2区 医学 Q1 SURGERY Pub Date : 2024-10-04 DOI: 10.1016/j.ajt.2024.09.033
Francesca Albanesi, Jae-Yoon Kim, Kwang-Woong Lee, YoungRok Choi, Nam-Joon Yi, Suk-Kyun Hong, Kyung-Suk Suh

Patients receiving liver transplantation in a setting of complete portal vein (PV) and superior mesenteric vein (SMV) thrombosis (Yerdel grade 4) experience lower outcomes after surgery; prognosis is independently influenced by the portal flow reconstruction technique, showing better outcomes in physiological surgical strategies. We describe a case of living donor liver transplantation in which the patient could not receive common physiological reconstructions preoperatively due to multiple small collaterals and extensive thrombosis down to first branches of SMV. We performed thromboendovenectomy of the PV and SMV first, but acute thrombosis developed recurrently even with interposition venous homograft between pericholedochal collateral vein and proximal recipient PV. Immediate after surgery, an intervention radiologist performed stent insertion into 3 stenotic points. Through multidisciplinary approach, complete physiological recanalization was obtained with normal liver function.

在门静脉(PV)和肠系膜上静脉(SMV)完全血栓形成(耶德尔4级)的情况下接受肝移植的患者术后预后较差;预后受门静脉血流重建技术的独立影响,生理手术策略的预后较好。我们描述了一例活体肝移植病例,患者术前无法接受普通的生理性重建,原因是存在多条小分支和SMV第一分支的广泛血栓形成。我们首先对门静脉和 SMV 进行了血栓内静脉切除术,但即使在胆总管旁静脉和受体门静脉近端之间进行了静脉同种异体移植,急性血栓仍反复形成。手术后,放射科介入医生立即对 3 个狭窄点进行了支架植入术。通过多学科合作,手术后肝功能恢复正常,实现了完全的生理性再通畅。
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引用次数: 0
Cytomegalovirus (CMV) Prophylaxis in Pediatric Liver Transplantation (PLT): A Comparison of Strategies Across the SPLIT Consortium. 小儿肝移植 (PLT) 中的巨细胞病毒 (CMV) 预防:SPLIT联盟的策略比较。
IF 8.9 2区 医学 Q1 SURGERY Pub Date : 2024-10-03 DOI: 10.1016/j.ajt.2024.09.025
Elizabeth D Knackstedt, Sarah G Anderson, Ravinder Anand, Jeff Mitchell, Ronen Arnon, Linda Book, Udeme Ekong, Scott A Elisofon, Katryn Furuya, Ryan Himes, Ajay K Jain, Nadia Ovchinsky, Shikha S Sundaram, John Bucuvalas, Lara Danziger-Isakov

Although cytomegalovirus (CMV) is a common complication after pediatric liver transplantation (PLT), the optimal method for CMV prevention is uncertain and lacks multi-centered investigation. We compared the effectiveness of short (<120d) versus long (>180d) CMV primary antiviral prophylaxis to prevent CMV disease in PLT, through a prospective cohort study of primary PLT (<18 yrs of age) recipients enrolled in the Society of Pediatric Liver Transplantation (SPLIT) registry from 2015 to 2019 with either donor or recipient CMV seropositivity. Participants were grouped into short or long prophylaxis based on their center's practice and intended duration. 199 PLT recipients were enrolled including 112 (56.3%) short and 87 (43.7%) long prophylaxis. End-organ disease was rare and similar between groups (2.7% and 1.1%; p=0.45). CMV DNAemia and syndrome were more common in the short compared to long (26.8% v. 13.8%; p=0.03 and 18.8% v. 6.9%; p=0.02). Neutropenia occurred more commonly with long prophylaxis (55.2% vs. 16.1%; p<0.001). Graft and patient survival were similar. Consideration of a short prophylaxis must weigh increased risk of CMV syndrome/DNAemia against medication burden and neutropenia of longer prophylaxis.

虽然巨细胞病毒(CMV)是小儿肝移植(PLT)后的常见并发症,但预防CMV的最佳方法尚不确定,也缺乏多中心调查。我们通过一项前瞻性队列研究比较了短期(180 天)CMV 初级抗病毒预防对预防小儿肝移植中 CMV 疾病的有效性。
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引用次数: 0
Abdominal normothermic regional perfusion after donation after circulatory death improves pancreatic islet isolation yield. 循环死亡后捐献腹腔常温区域灌注可提高胰岛分离率
IF 8.9 2区 医学 Q1 SURGERY Pub Date : 2024-10-02 DOI: 10.1016/j.ajt.2024.09.034
Jason B Doppenberg, Rutger M van Rooden, Madeleine C van Dijk, Femke H C de Goeij, Fenna J van der Heijden, Ian P J Alwayn, Eelco J P de Koning, Jeroen de Jonge, Marten A Engelse, Volkert A L Huurman

Abdominal normothermic regional perfusion (aNRP) is an in situ normothermic oxygenated donor perfusion technique before procurement during controlled donation after circulatory death (cDCD) procedures and allows for organ quality evaluation. There are few data on the effect of aNRP on pancreatic islet isolation and subsequent transplantation outcomes. We aim to evaluate the impact of aNRP on cDCD pancreatic islet isolation and transplantation. A retrospective analysis was performed on pancreatic islet isolation outcomes from aNRP, cDCD, and donation after brain death pancreases. Isolations were compared to previous donor age (60-75 years) matched isolations. Islet function was assessed by a dynamic glucose-stimulated insulin secretion. Donor baseline characteristics did not differ among groups. Isolations from aNRP pancreases (471 739 islet equivalents [IEQ] [655 435-244 851]) yielded more islets compared to cDCD (218 750 IEQ [375 951-112 364], P < .01) and to donation after brain death (206 522 IEQ [385 544-142 446], P = .03) pancreases. Dynamic glucose-stimulated insulin secretion tests in 7 aNRP islet preparations showed a mean stimulation index of 4.91, indicating good functionality. Bilirubin and alanine aminotransferase during aNRP correlated with islet yield (r2 = 0.685, P = .002; r2 = 0.491, P = .016, respectively). Islet isolation after aNRP in cDCD donors results in a high islet yield with viable functional islets. aNRP could increase the utilization of the pancreases for islet transplantation.

腹腔常温区域灌注(aNRP)是一种在循环死亡后受控捐献(cDCD)过程中进行器官采集前的原位常温氧合供体灌注技术,可用于器官质量评估。有关 aNRP 对胰岛分离和后续移植结果的影响的数据很少。我们旨在评估 aNRP 对 cDCD 胰岛分离和移植的影响。我们对 aNRP、cDCD 和脑死亡后捐献(DBD)胰腺的胰岛分离结果进行了回顾性分析。分离结果与之前捐献者年龄(60-75 岁)匹配的分离结果进行了比较。胰岛功能通过动态葡萄糖刺激胰岛素分泌(dGSIS)进行评估。各组供体的基线特征没有差异。与cDCD(218,750 IEQ [375,951 - 112,364,p2=0.685,p=0.002;r2=0.491,p=0.016)相比,从aNRP胰腺(471,739 IEQ [655,435 - 244,851])分离得到的胰岛更多。在对 cDCD 供体进行 aNRP 后进行胰岛分离,可获得具有存活功能的高胰岛产量。
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引用次数: 0
Gene expression-based molecular scoring of pancreas transplant rejection for a quantitative assessment of rejection severity and resistance to treatment. 基于基因表达的胰腺移植排斥反应分子评分,定量评估排斥反应严重程度和治疗耐受性。
IF 8.9 2区 医学 Q1 SURGERY Pub Date : 2024-09-28 DOI: 10.1016/j.ajt.2024.09.032
Audrey E Brown, Yvonne M Kelly, Arya Zarinsefat, Raphael P H Meier, Giulia Worner, Mehdi Tavakol, Minnie M Sarwal, Zoltan G Laszik, Peter G Stock, Tara K Sigdel

Pancreas transplantation improves glycemic control and mortality in patients with diabetes but requires aggressive immunosuppression to control the alloimmune and autoimmune response. Recent developments in "omics" methods have provided gene transcript-based biomarkers for organ transplant rejection. The tissue Common Response Module (tCRM) score is developed to identify the severity of rejection in kidney, heart, liver, and lung transplants. Still, it has not yet been validated in pancreas transplants (PT). We evaluated the tCRM score's relevance in PT and additional markers of acute cellular rejection (ACR) for PT. An analysis of 51 pancreas biopsies with ACR identified 37 genes and 56 genes significantly upregulated in the case of grade 3 and grade 2 ACR, respectively (P < .05). Significant differences were seen with higher grades of rejection among several transcripts. Of the 22 genes differentially expressed in grade 3 ACR, 18 were also differentially expressed in grade 2 ACR. The rejection signal was attributable to activated leukocytes' infiltration. Significantly higher tCRM scores were found in grade 3 ACR (P = .007) and grade 2 ACR (P = .004), compared to normal samples. The tCRM score was able to distinguish treatment-resistant cases from those successfully treated for rejection.

胰腺移植可改善糖尿病患者的血糖控制和死亡率,但需要积极的免疫抑制来控制同种免疫和自身免疫反应。最近,"omics "方法的发展为器官移植排斥提供了基于基因转录本的生物标志物。组织共同反应模块(tCRM)评分是为确定肾、心、肝和肺移植排斥反应的严重程度而开发的。但是,它尚未在胰腺移植(PT)中得到验证。我们评估了 tCRM 评分在胰腺移植中的相关性,以及胰腺移植急性细胞排斥反应(ACR)的其他标志物。我们对 51 例胰腺活检进行了分析,发现 3 级和 2 级 ACR 分别有 37 个和 56 个基因显著上调(P<0.05)。
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引用次数: 0
Portal inflow for liver transplantation when there is extensive portal and mesenteric thrombus 门静脉和肠系膜血栓广泛存在时,肝移植的门静脉入流
IF 8.9 2区 医学 Q1 SURGERY Pub Date : 2024-09-27 DOI: 10.1016/j.ajt.2024.03.029
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引用次数: 0
When is it safe to transplant after cancer-adding data to the decision. 癌症术后何时移植才安全--为决定添加数据。
IF 8.9 2区 医学 Q1 SURGERY Pub Date : 2024-09-27 DOI: 10.1016/j.ajt.2024.09.031
Steve Chadban, Kymberly D Watt
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引用次数: 0
The differential impact of early graft dysfunction in kidney donation after brain death and after circulatory death: Insights from the Dutch National Transplant Registry. 早期移植物功能障碍对脑死亡后和体外循环死亡后肾脏捐献的不同影响:来自荷兰国家移植登记处的启示。
IF 8.9 2区 医学 Q1 SURGERY Pub Date : 2024-09-27 DOI: 10.1016/j.ajt.2024.09.030
Thei S Steenvoorden, Lara Evers, Liffert Vogt, Janneke A J Rood, Jesper Kers, Marije C Baas, Maarten H L Christiaans, Jan H N Lindeman, Jan-Stephan F Sanders, Aiko P J de Vries, Arjan D van Zuilen, Frederike J Bemelman, Hessel Peters-Sengers

Kidneys donated after circulatory death (DCD) perform similarly to kidneys donated after brain death (DBD). However, the respective incidences of delayed graft function (DGF) differ. This questions the donor type-specific impact of early graft function on long-term outcomes. Using competing risk and Cox-regression analysis, we compared death-censored graft loss between types of early graft function: DGF (temporary dialysis dependency started within 7 days after transplantation), slow graft function (3-day plasma creatinine decline less than 10% per day), and immediate graft function. In 1061 DBD and 1605 DCD graft recipients (January 2014 until January 2023), graft survival was similar. DGF was associated with death-censored graft loss in DBD and DCD (adjusted hazard ratios: DGF in DBD: 1.79 [1.04-2.91], P = .027, DGF in DCD: 1.84 [1.18-2.87], P = .008; Reference: no DGF). Slow graft function was associated with death-censored graft loss in DBD, but not significantly in DCD (adjusted hazard ratios DBD: 2.82 (1.34-5.93), P = .007, and DCD: 1.54 (0.72-3.35), P = .262; Reference: immediate graft function). Early graft dysfunction has a differential impact on graft outcome in DBD and DCD. The differences between DBD and DCD should be accounted for in research and the clinic.

循环死亡(DCD)后捐献的肾脏与脑死亡(DBD)后捐献的肾脏表现相似。但是,移植肾功能延迟(DGF)的发生率却各不相同。这就对早期移植物功能对长期预后的特异性影响提出了质疑。利用竞争风险和 cox 回归分析,我们比较了不同类型早期移植物功能的死亡删失移植物损失:DGF(移植后七天内开始暂时性透析依赖)、缓慢移植物功能(SGF,三天血浆肌酐降幅每天小于 10%)和即时移植物功能(IGF)。在 1061 例 DBD 和 1605 例 DCD 移植物受者(2014 年 1 月至 2023 年 1 月)中,移植物存活率相似。在 DBD 和 DCD 中,DGF 与死亡剪除后的移植物损失相关(调整后危险比 [aHR]:DBD 中的 DGF:1.5%;DCD 中的 DGF:1.5%):DBD中的DGF:1.79 [1.04- 2.91],p = 0.027;DCD中的DGF:1.84 [1.18 - 2.87],p = 0.008;参考:无DGF)。在 DBD 中,SGF 与死亡剪除移植物损失相关,但在 DCD 中并不显著(aHR DBD:2.82 (1.34 - 5.93),p = 0.007;DCD:1.54 (0.72 - 3.35),p = 0.262;参考:IGF)。早期移植物功能障碍对 DBD 和 DCD 的移植物预后有不同的影响。在研究和临床中应考虑到 DBD 和 DCD 之间的差异。
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引用次数: 0
Association of nonstandardized model for end-stage liver disease score exceptions with waitlist mortality in adult liver transplant candidates. 成人肝移植候选者非标准化 MELD 评分异常与候选者死亡率的关系。
IF 8.9 2区 医学 Q1 SURGERY Pub Date : 2024-09-26 DOI: 10.1016/j.ajt.2024.09.028
Daniel J Ahn, Allison J Kwong, Anji E Wall, William F Parker

In the US liver allocation system, nonstandardized model for end-stage liver disease (MELD) exceptions (NSEs) increase the waitlist priority of candidates whose MELD scores are felt to underestimate their true medical urgency. We determined whether NSEs accurately depict pretransplant mortality risk by performing mixed-effects Cox proportional hazards models and estimating concordance indices. We also studied the change in frequency of NSEs after the National Liver Review Board's implementation in May 2019. Between June 2016 and April 2022, 60,322 adult candidates were listed, of whom 10,280 (17.0%) received an NSE at least once. The mean allocation MELD was 23.9, an increase of 12.0 points from the mean laboratory MELD of 11.9 (P < .001). A 1-point increase in allocation MELD score due to an NSE was associated with, on average, a 2% reduction in hazard of pretransplant death (cause-specific hazard ratio: 0.98; 95% CI: 0.96, 1.00; P = .02) compared with those with the same laboratory MELD. Laboratory MELD was more accurate than allocation MELD with NSEs in rank-ordering candidates (c-index: 0.889 vs 0.857). The proportion of candidates with NSEs decreased significantly after the National Liver Review Board from 21.5% to 12.8% (P < .001). NSEs substantially increase the waitlist priority of candidates with objectively low medical urgency.

在美国的肝脏分配系统中,非标准化的 MELD 例外情况会提高候选者的优先级,而这些候选者的 MELD 分数被认为低估了其真正的医疗紧迫性。我们通过混合效应 Cox 比例危险模型和估计一致性指数来确定 NSE 是否能准确描述移植前的死亡风险。我们还研究了国家肝脏审查委员会(NLRB)于 2019 年 5 月实施后 NSE 频率的变化。2016 年 6 月至 2022 年 4 月期间,60322 名成年候选人被列入名单,其中 10280 人(17.0%)至少接受了一次 NSE。分配 MELD 平均值为 23.9,比实验室 MELD 平均值 11.9 增加了 12.0 点(p < 0.001)。与实验室 MELD 相同的患者相比,NSE 导致的分配 MELD 评分每增加 1 分,移植前死亡风险平均降低 2%(病因特异性 HR 0.98,95% CI [0.96,1.00],p = 0.02)。在对候选者进行排序时,实验室 MELD 比带有 NSE 的分配 MELD 更准确(c 指数为 0.889 vs 0.857)。在 NLRB 之后,NSE 患者的比例从 21.5% 显著下降到 12.8%(p < 0.001)。NSE大大提高了客观上医疗紧迫性较低的候选者的候选优先级。
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引用次数: 0
FCGR2C Q13 and FCGR3A V176 alleles jointly associate with worse NK-cell mediated antibody-dependent cellular cytotoxicity and microvascular inflammation in kidney allograft antibody-mediated rejection. FCGR2C Q13和FCGR3A V176等位基因与肾移植抗体介导的排斥反应中NK细胞介导的抗体依赖性细胞毒性和微血管炎症的恶化密切相关。
IF 8.8 2区 医学 Q1 SURGERY Pub Date : 2024-09-25 DOI: 10.1016/j.ajt.2024.09.018
Elodie Bailly,Camila Macedo,Xinyan Gu,Deborah Hollingshead,Carol Bentlejewski,Erica Fong,Penelope A Morel,Parmjeet Randhawa,Adriana Zeevi,Carmen Lefaucheur,Diana Metes
NK cell-mediated antibody-dependent cell cytotoxicity (ADCC) is a major mechanism of humoral allograft injury. FCGR3A V176/F176 polymorphism influences ADCC activity. Additionally, NK cell FcγRIIc expression, dictated by the Q13/STP13 polymorphism, was never investigated in kidney transplantation. To assess the clinical relevance of FCGR2C Q13/STP13 polymorphism in conjunction with FCGR3A V176/F176 polymorphism, 242 kidney transplant recipients were genotyped. NK cell FcγR expression and ADCC activity were assessed. RNA sequencing was performed on kidney allograft biopsies to explore the presence of infiltrating FcγR+ NK cells. The FCGR2C Q13 allele was enriched in antibody-mediated rejection (ABMR) patients. FcγRIIc Q13+ NK cells had higher ADCC activity than FcγRIIc Q13- NK cells. In combination with the high-affinity FCGR3A V176 allele, Q13+V176+ NK cells were the most functionally potent. Q13+ was associated with worse microvascular inflammation and a higher risk of allograft loss. Among V176- patients, previously described in the literature as lower risk patients, Q13+V176- showed a lower graft survival than Q13-V176- patients. In ABMR biopsies, FCGR2C transcripts were enriched and associated with ADCC-related transcripts. Our results suggest that FCGR2C Q13 in addition to FCGR3A V176 is a significant risk allele that may enhance NK cell-mediated ADCC and contribute to allograft injury and poor survival.
NK 细胞介导的抗体依赖性细胞毒性(ADCC)是体液同种异体移植损伤的主要机制。FCGR3A V176/F176 多态性会影响 ADCC 活性。此外,由 Q13/STP13 多态性决定的 NK 细胞 FcγRIIc 表达在肾移植中从未被研究过。为了评估FCGR2C Q13/STP13多态性与FCGR3A V176/F176多态性的临床相关性,对242名肾移植受者进行了基因分型。对 NK 细胞 FcγR 表达和 ADCC 活性进行了评估。对肾移植活组织进行了 RNA 测序,以探究是否存在浸润的 FcγR+ NK 细胞。FCGR2C Q13等位基因在抗体介导的排斥反应(ABMR)患者中富集。FcγRIIc Q13+ NK细胞的ADCC活性高于FcγRIIc Q13- NK细胞。与高亲和力的 FCGR3A V176 等位基因结合,Q13+V176+ NK 细胞的功能最强。Q13+与更严重的微血管炎症和更高的异体移植损失风险有关。在以前文献中被描述为低风险患者的 V176- 患者中,Q13+V176- 患者的移植物存活率低于 Q13-V176- 患者。在ABMR活检中,FCGR2C转录本富集并与ADCC相关转录本相关。我们的研究结果表明,除FCGR3A V176外,FCGR2C Q13也是一个重要的风险等位基因,它可能会增强NK细胞介导的ADCC,导致异体移植物损伤和存活率低下。
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引用次数: 0
The Rochester Protocol for Living Donor Liver Transplantation of Unresectable Colorectal Liver Metastasis: A 5-Year Report on Selection, Approval, and Outcomes. 罗切斯特未切除大肠癌肝转移活体肝移植协议》:关于选择、批准和结果的五年报告。
IF 8.8 2区 医学 Q1 SURGERY Pub Date : 2024-09-25 DOI: 10.1016/j.ajt.2024.09.027
Matthew M Byrne,Mariana Chávez-Villa,Luis I Ruffolo,Anthony Loria,Yutaka Endo,Amber Niewiemski,Cristina Jimenez-Soto,Jennifer I Melaragno,Ramaraju Gopal,Priya D Farooq,Richard F Dunne,Karen Pineda-Solis,Amit Nair,Mark Orloff,Koji Tomiyama,Roberto Hernandez-Alejandro
Living donor liver transplantation (LDLT) is a treatment option for select patients with unresectable colorectal liver metastasis (uCRLM). We describe our center's experience of patient selection, insurance approval, and outcomes after LDLT after first referral in March 2019. Of the 206 evaluated patients, twenty-three underwent LDLT. We found that patients who were referred earlier in their oncologic course were more likely to be eligible for transplantation. After completion of the Rochester Protocol for LDLT eligibility, recipients had a median delay of care of 10 days (IQR 0-36) related to insurance appeal, with six patients (30%) having a delay longer than 30 days. LDLT recipients had an overall survival proportion of 100% and 91% at 1, and 3 years; and a recurrence-free survival proportion of 100% and 40%, at 1 and 3 years, respectively. All donors underwent right hepatectomy, of which only one donor had a Clavien-Dindo IIIa complication and readmission. There was no donor mortality. We assert that multidisciplinary care and strict patient selection through the Rochester Protocol were paramount to our center's success. In the appropriately selected patient, LDLT for uCRLM may be justified, and patients should be referred to transplant oncology centers for evaluation.
活体肝移植(LDLT)是不可切除结直肠肝转移(uCRLM)患者的一种治疗选择。我们介绍了本中心在2019年3月首次转诊后在患者选择、保险批准和LDLT术后疗效方面的经验。在 206 名接受评估的患者中,23 人接受了 LDLT。我们发现,在肿瘤病程早期转诊的患者更有可能符合移植条件。在完成罗切斯特 LDLT 资格认证协议后,受者因保险上诉而延误治疗的时间中位数为 10 天(IQR 0-36),其中 6 名患者(30%)的延误时间超过 30 天。LDLT受者1年和3年的总生存率分别为100%和91%;1年和3年的无复发生存率分别为100%和40%。所有捐献者都接受了右肝切除术,其中只有一名捐献者出现了 Clavien-Dindo IIIa 并发症并再次入院。没有出现捐献者死亡的情况。我们认为,多学科护理和通过罗切斯特协议严格选择患者是我们中心取得成功的关键。对于经过适当选择的患者,LDLT 治疗尿道癌可能是合理的,患者应转诊至肿瘤移植中心进行评估。
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引用次数: 0
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American Journal of Transplantation
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