Outcomes Following Extrahepatic and Intraportal Pancreatic Islet Transplantation: A Comparative Cohort Study
Outcomes Following Extrahepatic and Intraportal Pancreatic Islet Transplantation: A Comparative Cohort Study
复制标题
肝外和门内胰岛移植的结果：比较队列研究
作者：
K. Verhoeff;B. Marfil;G. Sandha;D. Cooper;K. Dajani;D. Bigam;B. Anderson;T. Kin;A. Lam;D. O’Gorman;P. Senior;C. Ricordi;A. M. Shapiro
背景初步研究显示肝外胰岛移植（ITx）的前景。然而，与门静脉内ITx结局的临床比较仍然有限。方法.这项单中心队列研究评估了1999年至2018年期间接受肝外或门静脉内ITx的患者。主要结果是刺激的C肽水平。次要结局为空腹血糖、BETA-2评分和空腹C肽水平。多变量logistic模型评估了与ITx后60天内早期移植物衰竭和原发性无功能复合变量独立相关的因素。结果在264例患者中，9例（3.5%）接受了肝外ITx（胃粘膜下= 2例，皮下= 3例，网膜= 4例）。基线时两组人口统计学特征相似（年龄、体重指数、糖尿病病程和血糖控制）。在首次输注后1-3个月，接受肝外ITx的患者具有显著较低的刺激C肽（0.05 nmol/L对1.2 nmol/L，P < 0.001），空腹血糖升高（9.3 mmol/L vs. 7.3 mmol/L，P < 0.001）和较低的BETA-2评分与接受门静脉内ITx的患者相比，SUITO指数（0比11.6，P < 0.001）和SUITO指数（1.5比39.6，P < 0.001）。接受肝外移植的受试者在移植后的前60天内未能产生中位数≥0.2 nmol/L的C肽。肝外移植后的门静脉内输注与单纯接受门静脉内移植的患者结局相当。肝外ITx与早期移植物衰竭/原发性无功能独立相关（优势比1.709，置信区间73.8-39 616.0，P < 0.001），而没有其他因素是独立预测因素。结论.使用目前的技术，门静脉内胰岛输注仍然是临床ITx的金标准，与人胰岛肝外移植相比，具有上级植入、移植物功能和血糖结果。
Background. Preliminary studies show promise for extrahepatic islet transplantation (ITx). However, clinical comparisons with intraportal ITx outcomes remain limited. Methods. This single-center cohort study evaluates patients receiving extrahepatic or intraportal ITx between 1999 and 2018. Primary outcome was stimulated C-peptide level. Secondary outcomes were fasting plasma glucose, BETA-2 scores, and fasting C-peptide level. Multivariable logistic modeling evaluated factors independently associated with a composite variable of early graft failure and primary nonfunction within 60 d of ITx. Results. Of 264 patients, 9 (3.5%) received extrahepatic ITx (gastric submucosal = 2, subcutaneous = 3, omental = 4). Group demographics were similar at baseline (age, body mass index, diabetes duration, and glycemic control). At 1–3 mo post–first infusion, patients receiving extrahepatic ITx had significantly lower stimulated C-peptide (0.05 nmol/L versus 1.2 nmol/L, P < 0.001), higher fasting plasma glucose (9.3 mmol/L versus 7.3 mmol/L, P < 0.001), and lower BETA-2 scores (0 versus 11.6, P < 0.001) and SUITO indices (1.5 versus 39.6, P < 0.001) compared with those receiving intraportal ITx. Subjects receiving extrahepatic grafts failed to produce median C-peptide ≥0.2 nmol/L within the first 60 d after transplant. Subsequent intraportal infusion following extrahepatic transplants achieved equivalent outcomes compared with patients receiving intraportal transplant alone. Extrahepatic ITx was independently associated with early graft failure/primary non-function (odds ratio 1.709, confidence interval 73.8-39 616.0, P < 0.001), whereas no other factors were independently predictive. Conclusions. Using current techniques, intraportal islet infusion remains the gold standard for clinical ITx, with superior engraftment, graft function, and glycemic outcomes compared with extrahepatic transplantation of human islets.