胰肾联合移植中供体切取和修整的技巧

目的:总结胰肾一期联合移植中供体胰十二指肠及肾脏切取及修整的经验。方法:回顾性分析19例胰肾联合移植术中供体胰十二指肠及肾脏切取的方法与移植物的修整技巧。结果:无1例发生移植物损伤。联合移植术后9 d之内18例完全停用外源性胰岛素,空腹血糖正常，尿糖≤（+）。术后2～4 d，血肌酐和尿素氮降至正常。3例出现移植肾脏急性排斥反应，2例发生移植胰腺急性排斥反应，给予甲泼尼龙冲击治疗后恢复正常。1例术后因移植物加速排斥反应，术后11 d切除移植胰、肾。结论:胰肾联合移植手术中，供体胰十二指肠及肾脏的切取及修整是手术成功的重要因素之一。     

胰腺、肾脏在单独和联合移植中排斥反应的差异

目的 比较胰腺、肾脏在单独和联合移植中排斥反应的差异。方法 在大鼠同种异体单独胰腺移植、单独肾脏移植和肺肾联合移植基础上,对胰腺、肾脏在单独和联合移植中的排斥瓜反应分别进行了比较。结果 （１）胰腺在联合肾脏移植中受到肾脏保护,与单独上比,功能与形态不者到显著改观;（２）肾脏在联合胰腺移植时未受到胰腺保护,与单独移植比较,各项指标未得到显著改善。结论 胰腺与肾脏联合移植的结局优于单独胰腺移植,而肾脏     

胰肾联合移植的排斥反应

目的　探讨胰肾联合移植术后的排斥反应。方法　对我院施行的 3例胰肾联合移植的病人 ,采用FK5 0 6 MMF Perid Zenapax四联免疫治疗方案 ,通过床边彩超及Cr、BUN、血糖等来监测移植物的排斥反应。对排斥反应采用激素冲击疗法 ,对激素不敏感者采用OKT3治疗。结果　3例患者中有 2例出现排斥反应 ,其发生率达 6 6 % ;在出现排斥反应时 ,首先表现为低热、全身不适 ,尿量减少 ,血Cr、BUN升高 ,彩超示移植物血流阻抗升高 ,之后才是血糖升高。结论　胰肾联合移植中 ,排斥反应与多种因素有关 ,移植肾对移植胰具有保护作用 ,肾脏可以作为监测胰腺排异的窗口 ,彩超检查可以作为筛选移植物排异反应的手段。     

胰肾联合移植的排斥反应

目的探讨胰肾联合移植术后的排斥反应。方法对我院施行的3例胰肾联合移植的病人，采用FK506 MMF Perid Zenapax四联免疫治疗方案，通过床边彩超及Cr、BUN、血糖等来监测移植物的排斥反应。对排斥反应采用激素冲击疗法，对激素不敏感者采用OKT3治疗。结果3例患者中有2例出现排斥反应，其发生率达66％；在出现排斥反应时，首先表现为低热、全身不适，尿量减少，血Cr、BUN升高，彩超示移植物血流阻抗升高，之后才是血糖升高。结论胰肾联合移植中，排斥反应与多种因素有关，移植肾对移植胰具有保护作用，肾脏可以作为监测胰腺排异的窗口，彩超检查可以作为筛选移植物排异反应的手段。     

胰、肾联合移植术式的选择

由于胰腺外分泌液的引流方式和移植胰腺排斥反应难以诊断的特殊性,胰、肾联合移植的总数和效果都远远落后于其它器官移植。直到最近十年,胰、肾联合移植的手术方式才趋向定型,成为治疗 1 型糖尿病合并尿毒症的最佳选择。在我国,胰、肾联合移植的经验积累十分有限,手术方式尚无统一标准,多数中心仅仅实施单一术式。因此,本文结合我们的经验,对胰腺与胰、肾联合移植手术选择的有关问题作一综述。一、胰、肾同期移植与肾移植后的胰腺移植胰、肾联合移植分为胰、肾同期移植(SPK)和肾移植后的胰腺移植(PAK),SPK的免疫学特点是胰腺和肾脏…     

移植胰腺活检的方法及其研究进展

<正>胰肾联合移植和胰腺移植已经成为治疗部分2型糖尿病和1型糖尿病的最佳方式。除了手术因素,术后管理是影响移植胰腺存活的重要因素之一,由于胰腺移植后的排斥反应缺乏特异性,排斥反应是胰腺移植后移植胰腺失功的重要因素之一^[1-2]。胰腺移植后排斥反应会导致胰酶升高,     

胰肾联合移植术后排斥反应分析

目的 探讨预防和逆转胰肾联合移植术后排斥反应的方法。方法 回顾性分析1999年9月～2003年9月17例同种异体胰肾联合移植手术患者的临床资料。全部病例采用口服免疫抑制剂：环孢素A、霉酚酸酯或硫唑嘌呤、激素三联用药。其中2例术前及术后第5天应用抗IL-2R单克隆抗体,3例应用OKT3进行免疫诱导。结果 17例患者中1例发生移植胰腺、肾脏加速性排斥反应．经保守治疗无效,切除移植物;8例发生急性排斥反应,其中单纯肾脏排斥反应6例,同时累及胰腺、肾脏的排斥反应2例,经甲泼尼龙或OKT3治疗后均逆转。结论 胰肾联合移植术后合理应用免疫抑制剂。术前采用综合措施降低高危受者的致敏性,是预防和治疗排斥反应的有效方法。     

胰腺和肝脏在联合移植时互惠作用的观察

作者对观察肝脏对胰腺的免疫保护作用和胰腺对肝脏的营养保护作用,采用大鼠单独胰腺移植,单独肝脏移植及肝胰联合移植进行研究。结果显示;胰腺联合肝脏移植时,胰腺平均功能存活期较单独移植时显著延长,间质排斥反应减轻,分级分布与单独移植相比差异有显著性意义;肝脏有联合移植时,术后再生能力以及形态的完整性估于单独移植。     

胰肾联合移植的外科技术探讨

目的 探讨胰液空肠引流式胰肾联合移植的外科技巧和临床应用.方法 中山大学附属第一医院2005年1月-2009年6月共施行了10例胰肾同期联合移植术(SPK),供体胰、十二指肠和肾均采用腹部多器官联合切取方式获得,经腹主动脉、肠系膜上静脉对胰腺及十二指肠同时快速灌注降温.移植胰的外分泌采用胰十二指肠一空肠内引流吻合方式.术后早期均以抗CD25单克隆抗体进行免疫诱导治疗,采用他克莫司、霉酚酸酯及皮质激素预防排斥反应.结果 10例移植手术均获得成功.供体胰十二指肠和肾的热缺血时间为(5.9±2.6)min;移植肾平均冷缺血时间为(5.2±2.2)h,移植胰平均冷缺血时间为(9.3±3.6)h.术后3例出现移植胰伤口感染,经治疗后3～12周愈合.2例出现胰十二指肠一空肠吻合口出血,均经保守治疗止血而治愈.未发生与胰液引流相关的外科并发症.1年内3例发生了急性排斥反应,2例经激素冲击和抗淋巴细胞球蛋白治疗而被逆转;1例顽固性急排患者术后39 d在持续肾脏替代治疗过程中并发脑血管意外死亡.其余9例均痊愈,随访6～12个月,完全停用胰岛素.结论 获取质量良好的供体器官及合理血管整形,是保证胰肾联合移植成功的前提;改进的胰液空肠外分泌引流术式的方法是可靠的.     

猪胰肾联合移植门静脉回流和体静脉回流术式对急性排斥反应的影响

目的 比较胰肾联合移植门静脉回流（PE）和体静脉回流（SE）两种术式对移植物急性排斥反应的影响.方法 48例无亲缘当地杂交第1代长白猪,随机分成PE组（24只）和SE组（24只）,每组内行交叉配血,相合者组成供受猪.切除受猪胰腺制成1型糖尿病模型,同时切除右肾.PE组门静脉与受猪肠系膜上静脉或门静脉行端侧吻合,SE组门静脉与受猪肝下下腔静脉吻合,外分泌均采用肠道引流.术后1、3、5、7 d监测血糖和移植肾尿液肌酐水平;术后3、7 d开腹取移植胰和肾组织行病理学检查,参照Nakhleh和Banff标准对移植胰腺和肾进行排斥反应评分.结果 PE组和SE组各行12例移植手术,两组移植物冷缺血时间差异无统计学意义[PE组为（231.25±19.86）min ;SE组为（234.60±15.80） min,P〉0.05].两组术后1、3、5、7 d血糖和移植肾尿液肌酐水平差异无统计学意义（P〉0.05）.SE组较PE组移植胰腺和肾急性排斥反应发生早且重,两组急性排斥反应病理评分差异有统计学意义（P〈0.05）.结论 猪胰肾联合移植内分泌PE与SE相比,可减轻和延缓急性排斥反应.     

Clinical experience with human anodal trypsinogen (HAT) for detection of pancreatic allograft rejection

Abstract To date one of the major dilemmas in clinical pancreas transplantation is the lack of a reliable indicator for pancreas rejection. In a consecutive series of 52 patients undergoing simultaneous pancreas and kidney (SPK) transplantation with bladder drainage technique between October 1991 and December 1992 a new test using serial levels of serum human anodal trypsinogen (HAT) was evaluated for its efficacy to detect pancreas rejection. Postoperative baseline levels of HAT were compared to peak HAT values at time of rejection. HAT profiles at time of rejection were calculated and compared to profiles of urinary amylase, serum amylase, fasting blood sugar and serum creatinine. In this series one year patient survival was 97%, graft survival of the pancreas 86% and of the kidney 90%. In 71% of the patients at least one rejection episode occurred. At time of kidney-biopsy proven rejection with a concurrent serum creatinine rise a significant HAT lCvel rise to more than 1000 ng/ml was observed from baseline levels of 200 ng/ml ( P < 0.001) indicating kidney and pancreas rejection (73%). Urinary amylase levels decreased in the majority of rejection episodes at the same time from baseline levels to less than 20000 U/l. In 25% of the rejection episodes a significant serum creatinine rise was observed without a HAT rise or urinary amylase decrease indicating kidney-only rejection, while in 2% a urinary amylase decrease and simultaneous HAT also was observed with a negative kidney biopsy indicating pancreas-only rejection. We feel that increase in HAT levels significantly correlates with pancreas rejection. After SPK, determination of HAT is an additional helpful non-invasive test. In pancreas transplantation alone HAT can be a useful indicator to detect rejection and facilitate timing of a pancreas biopsy and initiation of antirejection treatment.     

Apoptosis in kidney and pancreas allograft biopsies

BACKGROUND: Apoptosis is a particular form of cell death involved in the elimination of somatic cells. In this study, the occurrence of apoptotic cells in kidney and pancreas allograft biopsies was analyzed and correlated with the number of infiltrating macrophages and lymphocytes and granzyme B expression. METHODS: Kidney and pancreas biopsies from patients submitted to simultaneous pancreas-kidney transplantation were classified into three groups: acute rejection, chronic rejection, and transplant cases without evidence of rejection. Formalin-fixed paraffin biopsies were used to identify apoptosis by the terminal deoxynucleotidyl transferase [TdT]-mediated dUTP nick end labeling (TUNEL) method. RESULTS: In normal kidney, only few apoptotic cells were observed. In contrast, in kidney-allograft biopsies, the TUNEL signal was detected in the nuclei of tubular epithelial cells and also in mononuclear cells scattered in the interstitium. In pancreas biopsies, numerous apoptotic cells were detected in acinar cells, in ducts, and occasionally in islets. The number of apoptotic cells in acute pancreas rejection was significantly higher compared with acute rejection of kidney grafts (50+/-14 vs. 21+/-4 cells/mm2; P<0.05). In kidney biopsies, there was a positive correlation between apoptosis and macrophages (r=0.51; P<0.005), and apoptosis versus T lymphocytes (r=0.45; P<0.05). In pancreas biopsies, the number of apoptotic cells correlated only with the number of macrophages (r=0.41; P<0.05). CONCLUSIONS: Apoptosis occurs in kidney and pancreas allograft biopsies, markedly in acute rejection in pancreas biopsies. Although apoptosis may reflect a mechanism of down-regulation of the allograft immune response by eliminating infiltrating cells, the elimination of graft cells may result in graft damage, particularly in pancreas transplantation.     

Graft dysfunction in simultaneous pancreas kidney transplantation (SPK): Results of concurrent kidney and pancreas allograft biopsies

Simultaneous pancreas and kidney transplants offer significant therapeutic advantages but present a diagnostic approach dilemma in the diagnosis of rejection. Because both organs are from the same donor, the kidney has been treated traditionally as the “sentinel” organ to biopsy, presumably representing the status of both allografts. Truly concurrent biopsy studies, however, are needed to confirm this hypothesis. We examined 101 concurrent biopsies from 70 patients with dysfunction in either or both organs. Results showed concurrent rejection in 23 of 57 (40%) of cases with rejection; 19 of 57 (33.5%) and 15 of 57 (26.5%) showed kidney or pancreas only rejection, respectively. The degree and type of rejection differed in the majority (13 of 23, 56.5%) of cases with concurrent rejection, with the pancreas more often showing higher rejection grade. Taking into account pancreas dysfunction, a positive kidney biopsy should correctly predict pancreas rejection in 86% of the instances. However, the lack of complete concordance between the 2 organs, the discrepancies in grade and type of rejection, and the tendency for higher rejection grades in concurrent or pancreas only rejections, all support the rationale for pancreas biopsies. The latter provide additional data on the overall status of the organ, as well as information on nonrejection‐related pathologies.     

Morbidity of pancreas transplantation during cadaveric renal transplantation.

Simultaneous transplantation of the pancreas is an option for diabetic patients undergoing kidney transplantation to attempt to halt progression of diabetic complications, but the additional risk imposed by the procedure is unclear. Our aim was to determine the morbidity attributable to pancreas transplantation during simultaneous pancreas and kidney transplantation. We compared the first posttransplant year of 18 consecutive recipients of combined pancreas and kidney transplantation to 18 consecutive recipients of kidney transplantation alone. All patients received cadaver donor allografts between 1986 and 1989, and had type I diabetes mellitus with chronic renal failure. There were no differences in patient survival (94% both groups) or satisfactory renal allograft function (89% pancreas/kidney group, 83% kidney group) up to 18 months after transplantation. Eighty-eight percent of pancreas allografts were functioning satisfactorily at 18 months. There was a mean (+/- SD) of 1.5 +/- 1.0 acute rejection episodes per patient for the pancreas/kidney group compared to 0.8 +/- 6 for the kidney-only group (P less than 0.02). Cytomegalovirus infection and wound complications were each encountered more often after pancreas/kidney transplantation than kidney transplantation alone, and together with rejection accounted for a difference in days of hospitalization during the first year (71 +/- 34 vs. 27 +/- 13, P less than 0.001). We conclude that simultaneous pancreas transplantation during cadaver donor kidney transplantation accounted for more frequent rejection episodes, CMV infections, and wound complications. These complications resulted in more hospitalization for patients undergoing simultaneous pancreas/kidney transplantation than kidney transplantation alone.     

En bloc transplantation of the liver, pancreas, duodenum, spleen, and kidney in the rat.

Five organs consisting of the liver, pancreas, duodenum, spleen, and kidney from (Lewis X Brown Norway)F1 rats were transplanted simultaneously as an en bloc graft to Lewis recipients. No immunosuppression was given postoperatively. Serial laporatomies were performed for macroscopic examination and biopsies of the grafts. Macroscopically, the first evidence of rejection was splenic enlargement followed by fatty metamorphotic change of the liver, dilation and loss of peristalsis of the duodenum, and injection of the pancreas. The kidney maintained normal color and consistency until late in the rejection process. Histological examination suggested that the liver and the spleen may be more vulnerable to immune attack, since in these organs cellular infiltration started earlier and was more extensive in comparison to other organs. While the pancreas exhibited a typical, although somewhat delayed rejection pattern, the kidney seemed to maintain a well preserved structure. Interestingly, the duodenum showed no significant cellular infiltration throughout the postoperative period of examination despite severe mucosal destruction.     

Outcomes of simultaneous kidney-pancreas transplantation in African-American recipients: a case-control study

INTRODUCTION: Previous studies have suggested that African-American (AA) ethnicity is a risk factor for rejection and graft loss after kidney transplantation. However, little data is available regarding outcomes after simultaneous kidney pancreas transplantation (SKPT) in AA recipients. The objective of this study was to compare the outcomes of SKPT in AA patients to matched Caucasian patients as controls. METHODS: From January 1996 to September 1999, we performed 79 SKPTs, including 10 in AA recipients. Ten Caucasian controls were selected and matched for age, gender, weight, timing and technique of transplantation, and immunosuppressive regimen. Clinical outcomes were collected and compared between the two groups. RESULTS: The two groups were well matched for donor and recipient demographic, immunologic and transplant characteristics, including 2 patients in each group with type 2 diabetes. All patients received tacrolimus (TAC), mycophenolate mofetil (MMF) and steroids, and about half in each group received antibody induction therapy. Patient survival was 100% in both groups with a mean follow-up of 18 months (range 6 47). Kidney and pancreas graft survival rates were both 80% in the AA and 100% in the Caucasian groups, respectively (p = 0.14). All but one kidney (in the AA group) and all pancreas grafts experienced immediate function. There were two immunologic kidney and two immunologic pancreas graft losses in the AA group. No grafts were lost due to technical problems. The mean length of initial hospital stay was 16 d in the AA group compared to 10 d in the Caucasian group (p = 0.07). The AA group had a slight increase in the number of readmissions (mean 2.2 AA vs. 1.6 Caucasian, p = 0.08). The incidence of biopsy-proven pancreas acute rejection was significantly higher in the AA group (50%) compared to the Caucasian group (10%) (p = 0.05). The incidence of either kidney or pancreas acute rejection was also higher in the AA group (60% AA vs. 20% Caucasian, p = 0.06). TAC levels were comparable at specific times after transplantation, al-though there was a trend toward higher doses of TAC in the AA group to achieve therapeutic levels. The incidences of relaparotomy (30% AA vs. 20% Caucasian) and major infection (40% AA vs. 60% Caucasian) were similar between groups. Renal and pancreas allograft functions were comparable between groups at specific times after transplantation. CONCLUSIONS: These results suggest that SKPT in AA recipients may be associated with a higher incidence of rejection and immunologic graft loss compared to matched Caucasian controls.     

Serial peripheral blood cytotoxic lymphocyte gene expression measurements for prediction of pancreas transplant rejection

Acute rejection after pancreas transplantation remains a significant problem and contributes to immunological graft loss. No clinical markers of pancreas rejection have been universally accepted. The purpose of this study was to investigate the use of genetic markers; granzyme B, perforin, and HLA-DRA in the peripheral blood of pancreas transplant recipients. These genes have been identified in renal and islet cell transplant recipients as noninvasive tools to predict acute rejection. Blood samples were collected weekly for up to 1 year posttransplant. Surveillance biopsies of the pancreas were scheduled at weeks 2, 4, 8, and 12 as part of the typical posttransplant protocol for patients with pancreas alone or pancreas after kidney transplantation. Exclusion criteria included a diagnosis of biopsy-proven chronic rejection alone, pancreatitis, or kidney rejection within 2 months after pancreas biopsy. Gene expression levels of granzyme B, perforin, and HLA-DRA were compared in patients with (n = 7) and without biopsy proven acute rejection (n = 7). Recipients with acute rejection showed increased expression of granzyme B, HLA-DRA, as well as perforin genes compared to patients without biopsy-proven rejection. In addition, we observed that elevation of these genes occurred as early as 4 weeks before the traditional biopsy diagnosis, while the recipients with no rejection showed no change in gene expression. Our data indicated that serial measurements of peripheral blood granzyme B, perforin, and HLA-DRA gene expression can be a useful tool to predict pancreas rejection in its earliest stage.     

Differential effects of preexisting uremia and a synchronous kidney graft on pancreas allograft functional survival in rats.

Pancreas transplant results have been better in uremic recipients of a simultaneous kidney than in nonuremic recipients of a pancreas alone. We studied the relative effect of uremia versus a double transplant on functional survival by performing bladder-drained pancreas transplants alone (PTA), kidney transplants alone (KTA), and simultaneous pancreas/kidney (SPK) transplants from Buffalo donors to diabetic Lewis rat recipients that were or were not made uremic 2-3 weeks before by 1 4/5 native nephrectomy. Pancreas graft exocrine function was monitored by urinary amylase (UA). In the PTA and SPK recipients made diabetic by streptozotocin, endocrine function was monitored by measuring nonfasting plasma glucose (PG) levels. Kidney graft function was monitored by plasma creatinine (Cr). Rejection of the endocrine pancreas was defined as an increase of PG to greater than 200 mg/dl; of the exocrine pancreas, as a decline in UA to less than 6000 U/L or to less than 100 U/24 hr; and of the kidney, as an elevation of Cr to greater than 3 mg/dl. The mean functional survival times (MST) of both the endocrine (12.0 +/- 2.1 versus 10.1 +/- 1.1 days, P = 0.036) and exocrine (8.0 +/- 2.1 versus 6.3 +/- 1.3 days, P = 0.016) components of the pancreas grafts were significantly longer in SPK than in PTA recipients. The MST of kidney allografts, however, was not significantly longer in nonuremic SPK than nonuremic KTA recipients (6.7 +/- 1.4 versus 5.7 +/- 0.7 days, P = 0.13). In parallel experiments in recipients immunosuppressed with cyclosporine, the graft survival times were longer, but the relative differences between the PTA, SPK, and KTA groups persisted. Histologically, lymphocyte infiltration began in the two organs almost simultaneously, but the severity of the rejection was more vigorous in the kidney than in the pancreas in doubly grafted rats, and destruction of pancreas grafts progressed more slowly in SPK than in PTA recipients. Preexisting uremia delayed pancreas rejection in both SPK (exocrine 10.6 +/- 2.3, P = 0.032, and endocrine 14.8 +/- 3.4 days, P = 0.065, versus nonuremics) and PTA (exocrine 8.5 +/- 1.7, P = 0.007, and endocrine 12.6 +/- 2.5, P = 0.026, versus nonuremics) nonimmunosuppressed recipients. The MST of kidney grafts was not significantly longer in uremic (8.9 +/- 2.8 days) than in nonuremic (6.7 +/- 1.4 days) SPK recipients (P = 0.081). A synchronous kidney transplant and uremia independently down-modulate the rejection response to a pancreas graft, and a simultaneous pancreas graft has no detrimental effect on the survival of a kidney graft.(ABSTRACT TRUNCATED AT 400 WORDS)