Gruessner Angelika C, Sutherland David E R
IPTR, Diabetes Institute for Immunology and Transplantation, Department of Surgery, University of Minnesota, Minneapolis, MN 55455, USA.
Clin Transplant. 2005 Aug;19(4):433-55. doi: 10.1111/j.1399-0012.2005.00378.x.
As of December 31, 2004, more than 23,000 pancreas transplant had been reported to the IPTR, >17,000 in the US and almost 6000 from outside the US. An analysis of US pancreas transplants performed between 1988 and 2003 showed a progressive improvement in outcome, with pancreas transplant graft survival rates (GSRs) going from 75% at 1 yr for 1988/1989 to 85% for 2002/2003 simultaneous pancreas-kidney (SPK) cases, from 55 to 78% for pancreas after kidney (PAK) cases, and from 45 to 77% for pancreas transplants alone (PTA) cases. The improvements were due both to decreases in technical failure (TF) rates (from 12 to 6% in SPK, 13-8% in PAK, and 24-7% in PTA) and immunological failure rates (going from 7 to 2% for SPK, from 28 to 7% for PAK, and from 38 to 8% for PTA cases). These results are even more impressive under the aspect that during the same time the rate of potential risk factors increased and the duct management techniques changed from bladder to enteric drainage. The improvement in outcome allowed also an increase in the number of solitary pancreas transplants from initially 12% to now 35%. Contemporary primary deceased donor pancreas transplant outcomes were calculated separately for 2000-2004 US and non-US cases. The US patient survival rates at 1 yr were >95% in each recipient category, with 1 yr primary pancreas GSRs of 85% for SPK, 78% for PAK, and 76% for PTA (p < 0.0001). The immunological graft failure rates for 2000-2004 technically successful (TS) SPK, PAK, and PTA cases were 2, 8, and 10% at 1 yr (p = 0.0001). In the majority of all transplants ED was used for duct management (81% of SPK, 67% of PAK, and 56% for PTA cases). Of the ED transplants, venous drainage via the portal system was used for 20% of SPK, 23% of PAK, and 35% of PTA cases. Duct management technique did not have a significant impact on overall pancreas graft function in the univariate or the multivariate model. The outcomes of ED and BD transplants are comparable with 85 vs. 87% at 1 yr for SPK, 77 vs. 80% for PAK, and 72 vs. 79% for PTA. The overall TF rate was higher in ED pancreas transplants but this difference did reach significance only in SPK. In addition, in technically successful PTA the immunological graft loss rate was higher in ED vs. BD transplants (15 vs. 5% at 1 yr). The different vascular management techniques did not seem to have an impact on the outcome of the pancreas transplants. Kidney GSRs were not significantly different for ED vs. BD SPK cases, 93 and 91% at 1 yr (p = 0.24). The overall conversion rate from BD to ED was 9% at 1 yr and 17% at 3 yr post-transplant. The most influential factor for patient survival in SPK and PAK in the multivariate and the univariate models was the status of the transplanted organ. The hazard ratio (HR) for a failed kidney was 14.99 in SPK and 9.17 in PAK (p = 0.0001). The HR for a failed pancreas graft was 3.51 in SPK and 4.17 for PAK (p = 0.0001). In PTA a failed pancreas graft did not have a direct impact on patient survival. SPK and PAK patients older than 44 yr at the time of transplants also showed an increased mortality risk, but at the same time the risk of immunological graft loss was significantly decreased for those patients. TAC&MMF remained the dominant maintenance immunosuppressant for 2000-2004 US cases (approximately two-third) in all three categories and with this regime 1-year GSRs were > or =80% in all three recipient categories. The results were comparable (> or =83% 1-year GSR) for patients (approximately 10%) treated with Sirolimus (SIR) under various protocols. In regard to non-US pancreas transplants, even for 2000-2004 the overwhelming majority continued to be in the SPK category (91%), with 1-year patient, kidney and pancreas survival rates of 94, 92, and 87%. Solitary transplants are still very rarely done outside the US. Non-US PAK GSR at 1 yr was 85%, non-US PTA GSR at 1 yr was 76%. In summary, with the new advancements in immunosuppression and changes in surgical techniques the outcomes in patient survival and pancreas transplant graft function continue to improve even with an increasing proportion of high risk patients in all three categories.
截至2004年12月31日,国际胰腺移植登记处(IPTR)共收到超过23,000例胰腺移植报告,其中美国有17,000多例,美国以外地区近6000例。对1988年至2003年在美国进行的胰腺移植分析显示,移植效果有了逐步改善,同期胰腺移植的移植物存活率(GSR)如下:1988/1989年同期胰肾联合移植(SPK)1年时为75%,2002/2003年升至85%;肾后胰腺移植(PAK)从55%升至78%;单纯胰腺移植(PTA)从45%升至77%。这些改善归因于技术失败(TF)率的降低(SPK从12%降至6%,PAK从13%降至8%,PTA从24%降至7%)和免疫失败率的降低(SPK从7%降至2%,PAK从28%降至7%,PTA从38%降至8%)。在同一时期潜在危险因素增加且导管管理技术从膀胱引流改为肠道引流的情况下,这些结果更令人印象深刻。移植效果的改善也使单纯胰腺移植的数量从最初的12%增加到现在的35%。分别计算了2000 - 2004年美国和非美国的当代原发性脑死亡供体胰腺移植结果。美国各受者类别1年时的患者存活率均>95%,SPK的1年原发性胰腺GSR为85%,PAK为78%,PTA为76%(p < 0.0001)。2000 - 2004年技术成功(TS)的SPK、PAK和PTA病例1年时的免疫移植物失败率分别为2%、8%和10%(p = 0.0001)。在所有移植中,大多数采用肠道引流(ED)进行导管管理(SPK为81%,PAK为67%,PTA为56%)。在采用ED的移植中,20%的SPK、23%的PAK和35%的PTA病例通过门静脉系统进行静脉引流。在单变量或多变量模型中,导管管理技术对整体胰腺移植物功能没有显著影响。ED和膀胱引流(BD)移植的结果具有可比性,SPK 1年时分别为85%和87%,PAK为77%和80%,PTA为72%和79%。ED胰腺移植的总体TF率较高,但这种差异仅在SPK中具有统计学意义。此外,在技术成功的PTA中,ED移植的免疫移植物丢失率高于BD移植(1年时分别为15%和5%)。不同的血管管理技术似乎对胰腺移植结果没有影响。ED和BD的SPK病例肾GSR在1年时无显著差异,分别为93%和9!%(p = 0.24)。移植后1年从BD转换为ED的总体转换率为9%,3年时为17%。在多变量和单变量模型中,影响SPK和PAK患者存活的最主要因素是移植器官的状态。肾移植失败的风险比(HR)在SPK中为14.99,在PAK中为9.17(p = 0.0001)。胰腺移植物失败的HR在SPK中为3.51,在PAK中为4.17(p = 0.0001)。在PTA中,胰腺移植物失败对患者存活没有直接影响。移植时年龄大于44岁的SPK和PAK患者死亡风险也增加,但同时这些患者免疫移植物丢失的风险显著降低。2000 - 2004年美国病例中,他克莫司(TAC)和霉酚酸酯(MMF)仍然是所有三个类别中主要的维持性免疫抑制剂(约三分之二),采用这种方案,所有三个受者类别1年GSR均>或 = 80%。接受西罗莫司(SIR)不同方案治疗的患者(约10%)结果与之相当(1年GSR>或 = 83%)。关于非美国的胰腺移植,即使在2000 - 2004年,绝大多数仍为SPK类别(91%),1年患者、肾和胰腺存活率分别为94%、92%和87%。在美国以外地区,单纯移植仍然很少进行。非美国PAK 1年GSR为85%,非美国PTA 1年GSR为7!%。总之,随着免疫抑制的新进展和手术技术的改变,即使所有三个类别中高风险患者的比例增加,患者存活和胰腺移植移植物功能的结果仍在继续改善。