Progress in pancreas transplantation and combined pancreas-kidney transplantation

BACKGROUND: Pancreas transplantation (PT) has proved effective but it is associated with a high risk of surgical complications and technical failure. Duct management and venous drainage are identified as major issues. Improvements in immunosuppression and prophylaxis greatly have contributed to surgical progress. DATA SOURCES: A literature search of the PubMed database (1996-2005) was conducted and research articles on PT reviewed. RESULTS: More than 23 000 PTs have been performed throughout the world. The majority (83%) were performed in combination with kidney transplantation [simultaneous pancreas-kidney transplantation (SPK)]. Pancreas graft survival rates at one year were 85% for 2001-2003 SPK cases, 79% for pancreas after kidney transplantation (PAK) cases, and 76% for pancreas transplantation alone (PTA) cases. For the 1999-2003 cases, enteric drainage was done in 79% of the SPK cases and bladder drainage in 21%. Patient survival rates, pancreas and kidney graft survival rates, and pancreas graft immunological failure rates did not differ significantly in enteric versus bladder drainage cases. All the available data fail to demonstrate a definitive advantage of portal drainage over systemic drainage. From 1993 to 2002, the use of rabbit antithymocyte globulin increased from 0 to 37%; the use of daclizumab increased from 0 to 16%; and the use of basiliximab increased from 0 to 25%. In 1993, 98% of SPK recipients received cyclosporine; but this was decreased to 9% in 2002. Tacrolimus (FK506) usage has increased from 0 (1993) to 87% (2002) of SPK recipients. Sirolimus (SIR) usage has increased from 0 (1993) to 18% (2002) of SPK recipients. CONCLUSIONS: PT remains an effective therapy for treatment of type I diabetes mellitus. Enteric drainage is currently predominant in SPK, but bladder drainage is still largely used. Portal drainage is as safe as systemic drainage, but there is still no convincing evidence about whether it is immunologically or metabolically convenient. The combined of FK506 and mycophenolate mophetil (MMF) is the preferred maintenance immunosuppression in PT. Sirolimus may be a good alternative as a second agent in recipients of PT under FK506 therapy.

Establishment of a pig model of combined pancreas-kidney transplantation

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Simultaneous pancreas-kidney transplantation with modified enteric drainage of exocrine pancreatic secretion

BACKGROUND: As a valid therapeutic option for patients with type 1 diabetes mellitus (IDDM) and secondary dia- betic nephropathy, simultaneous pancreas-kidney trans- plantation (SPK) remains more undeveloped than other solid organ transplantations due to the restrictions of surgi- cal techniques especially the modes of exocrine pancreatic secretion. The aim of this paper was to summarize our sin- gle-center experience in SPK with modified enteric drai- nage (ED). METHODS: From June 2000 to July 2003, 10 patients with IDDM associated with uremia received SPK. The pancrea- tic allograft exocrine secretion was drained into the proxi- mal jejunum via a side-to-side duodenojejunostomy with- out Roux-en-Y anastomosis. Quadruple immunosuppres- sive regimen consisted of induction of tacrolimus (TAC) / cyclosporine (CsA), mycophenolate mofetil (MMF), ste- roids and antibodies, which included antilymphocyte glo- bulin (ALG) or anti-CD25 monoclonal antibody. RESULTS: ED-SPK without Roux-en-Y anastomosis was successful in all 10 patients without serious complications such as pancreatitis, graft thrombosis and pancreatic fistu- la. The patients regained immediate kidney allograft func- tion and euglycemia with insulin-independence. Four pa- tients survived over one year. Episodes of acute rejection were observed in 4 patients, 3 of whom showed reversion after treatment of OKT3 or insulin. Early postoperative complications included peritoneal infection ( 2 patients ), wound infection (2) and renal hematoma (1). CONCLUSION: ED-SPK without Roux-en-Y anastomosis is safe and preferable to the patients with IDDM associated with uremia.

Use of surgical techniques in the rat pancreas transplantation model

BACKGROUND: Pancreas transplantation is currently considered to be the most reliable and effective treatment for insulin-dependent diabetes mellitus (also called type I diabetes). With the improvement of microsurgical techniques, pancreas transplantation in rats has been the major model for physiological and immunological experimental studies in the past 20 years. We investigated the surgical techniques of pancreas transplantation in rats by analysing the difference between cervical segmental pancreas transplantation and abdominal pancreaticoduodenal transplantation. METHODS: Two hundred and forty male adult Wistar rats weighing 200-300 g were used, 120 as donors and 120 as recipients. Sixty cervical segmental pancreas transplants and 60 abdominal pancreaticoduodenal transplants were carried out and vessel anastomoses were made with microsurgical techniques. RESULTS: The time of donor pancreas harvesting in the cervical and abdominal groups was 31 6 and 37.6 +/- 3.8 min, respectively, and the lengths of recipient operations were 49.2 +/- 5.6 and 60.6 +/- 7.8 min. The time for donor operation was not significantly different (P > 0.05), but the recipient operation time in the abdominal group was longer than that in the cervical group (P < 0.05). In isograft transplantation without any preconditioning, I-week survival rates were 93.6% and 86.2% in the cervical and abdominal groups, respectively, and were not significantly different (P > 0.05). CONCLUSIONS: Both pancreas transplantation methods are stable models for immunological and physiological studies in pancreas transplantation. Since each has its own advantages and disadvantages, the designer can choose the appropriate method according to the requirements of the study.

Autoimmune diabetes recurrence should be routinely monitored after pancreas transplantation

Autoimmune type 1 diabetes recurrence in pancreas grafts was first described 30 years ago, but it is not yet completely understood. In fact, the number of transplants affected and possibly lost due to this disease may be falsely low. There may be insufficient awareness to this entity by clinicians, leading to underdiagnosis. Some authors estimate that half of the immunological losses in pancreas transplantation are due to autoimmunity. Pancreas biopsy is the gold standard for the definitive diagnosis. However, as an invasive procedure, it is not the ideal approach to screen the disease. Pancreatic autoantibodies which may be detected early before graft dysfunction, when searched for, are probably the best initial tool to establish the diagnosis. The purpose of this review is to revisit the autoimmune aspects of type 1 diabetes and to analyse data about the identified autoantibodies, as serological markers of the disease. Therapeutic strategies used to control the disease, though with unsatisfactory results, are also addressed. In addition, the author's own experience with the prospective monitoring of pancreatic autoantibodies after transplantation and its correlation with graft outcome will be discussed.

Human parvovirus B19-associated early postoperative acquired pure red cell aplasia in simultaneous pancreas-kidney transplantation:A case report

BACKGROUND Acquired pure red cell aplasia(aPRCA)related to human parvovirus B19(HPV B19)is rarely reported in simultaneous pancreas-kidney transplantation(SPKT)recipients;there has yet to be a case report of early postoperative infection.In this current study,we report the case of a Chinese patient who experienced the disease in the early postoperative period.CASE SUMMARY A 63-year-old man,with type 2 diabetes and end-stage renal disease,received a brain dead donor-derived SPKT.Immunosuppression treatment consisted of tacrolimus,prednisone,enteric-coated mycophenolate sodium(EC-MPS),and thymoglobulin combined with methylprednisolone as induction.The hemoglobin(Hb)level declined due to melena at postoperative day(POD)3,erythropoietinresistant anemia persisted,and reticulocytopenia was diagnosed at POD 20.The bone marrow aspirate showed decreased erythropoiesis and the presence of giant pronormoblasts at POD 43.Metagenomic next-generation sequencing(mNGS)of a blood sample identified HPV B19 infection at POD 66.EC-MPS was withdrawn;three cycles of intravenous immunoglobulin(IVIG)infusion therapy were administered;and tacrolimus was switched to cyclosporine.The HPV B19-associated aPRCA resolved completely and did not relapse within the 1-year follow-up period.The diminution in mNGS reads was correlated with Hb and reticulocyte count improvements.CONCLUSION HPV B19-associated aPRCA can occur at an early period after SPKT.An effective therapy regimen includes IVIG infusion and adjustment of the immunosuppressive regimen.Moreover,mNGS can be used for the diagnosis and to reflect disease progression.

Combined en bloc liver/pancreas transplantation in two different patients

Combined en bloc liver/pancreas transplantation(CLPT) was used primarily in the treatment of otherwise non-resectable upper abdominal malignancy.In fact, a more appropriate indication is in patients with liver disease and insulin-dependent diabetes mellitus(IDDM).Here, we report on two successful cases of CLPT at our hospital.One was a patient with non-resectable advanced liver cancer.The recipient survived for 23 mo and finally died of recurrent tumor.The other was a patient with severe biliary complication after orthotopic liver transplantation and preoperative IDDM.We performed CLPT with a modifi ed surgical technique of preserving the native pancreas.He is currently liver-disease-and insulin-free more than 27 mo post-transplant.Based on our experience in two cases of abdominal cluster transplantation, we describe the technical details of CLPT and a modif ication of the surgical procedure.

Anticoagulation in simultaneous pancreas kidney transplantation - On what basis?

BACKGROUND Despite technical refinements,early pancreas graft loss due to thrombosis continues to occur.Conventional coagulation tests(CCT)do not detect hypercoagulability and hence the hypercoagulable state due to diabetes is left untreated.Thromboelastogram(TEG)is an in-vitro diagnostic test which is used in liver transplantation,and in various intensive care settings to guide anticoagulation.TEG is better than CCT because it is dynamic and provides a global hemostatic profile including fibrinolysis.AIM To compare the outcomes between TEG and CCT(prothrombin time,activated partial thromboplastin time and international normalized ratio)directed anticoagulation in simultaneous pancreas and kidney(SPK)transplant recipients.METHODS A single center retrospective analysis comparing the outcomes between TEG and CCT-directed anticoagulation in SPK recipients,who were matched for donor age and graft type(donors after brainstem death and donors after circulatory death).Anticoagulation consisted of intravenous(IV)heparin titrated up to a maximum of 500 IU/h based on CCT in conjunction with various clinical parameters or directed by TEG results.Graft loss due to thrombosis,anticoagulation related bleeding,radiological incidence of partial thrombi in the pancreas graft,thrombus resolution rate after anticoagulation dose escalation,length of the hospital stays and,1-year pancreas and kidney graft survival between the two groups were compared.RESULTS Seventeen patients who received TEG-directed anticoagulation were compared against 51 contemporaneous SPK recipients(ratio of 1:3)who were anticoagulated based on CCT.No graft losses occurred in the TEG group,whereas 11 grafts(7 pancreases and 4 kidneys)were lost due to thrombosis in the CCT group(P=0.06,Fisher’s exact test).The overall incidence of anticoagulation related bleeding(hematoma/gastrointestinal bleeding/hematuria/nose bleeding/re-exploration for bleeding/post-operative blood transfusion)was 17.65%in the TEG group and 45.10%in the CCT group(P=0.05,Fisher’s exact test).The incidence of radiologically confirmed partial thrombus in pancreas allograft was 41.18%in the TEG and 25.50%in the CCT group(P=0.23,Fisher’s exact test).All recipients with partial thrombi detected in computed tomography(CT)scan had an anticoagulation dose escalation.The thrombus resolution rates in subsequent scan were 85.71%and 63.64%in the TEG group vs the CCT group(P=0.59,Fisher’s exact test).The TEG group had reduced blood product usage{10 packed red blood cell(PRBC)and 2 fresh frozen plasma(FFP)}compared to the CCT group(71 PRBC/10 FFP/2 cryoprecipitate and 2 platelets).The proportion of patients requiring transfusion in the TEG group was 17.65%vs 39.25%in the CCT group(P=0.14,Fisher’s exact test).The median length of hospital stay was 18 days in the TEG group vs 31 days in the CCT group(P=0.03,Mann Whitney test).The 1-year pancreas graft survival was 100%in the TEG group vs 82.35%in the CCT group(P=0.07,log rank test)and,the 1-year kidney graft survival was 100%in the TEG group vs 92.15%in the CCT group(P=0.23,log tank test).CONCLUSION TEG is a promising tool in guiding judicious use of anticoagulation with concomitant prevention of graft loss due to thrombosis,and reduces the length of hospital stay.

PREVENTION AND TREATMENT OF REJECTION AFTER SIMULTANEOUS PANCREAS-KIDNEY TRANSPLANTATION

Objective To explore methods of preventing and reversing rejection after simultaneous pancreas-kidney (SPK) tran- splantation. Methods Seventeen patients underwent SPK transplantation from September 1999 to September 2003 were reviewed retrospectively. Immunosuppression was achieved by a triple drug regimen consisting of cyclosporine, mycophenolate mofteil (MMF), and steroids. Three patients were treated with anti-CD3 monoclone antibody (OKT3, 5 mg·d-1) for induction therapy for a mean period of 5-7 days. One patients received IL-2 receptor antibodies (daclizumab) in a dose of 1 mg·kg-1 on the day of transplant and the 5th day posttransplant. One patient was treated with both OKT3 and daclizumab for induction. Results No primary non-functionality of either kidney or pancreas occurred in this series of transplantations. Function of all the kidney grafts recovered within 2 to 4 days after transplantation. The level of serum creatinine was 94 ± 11 μmol/L on the 7th day posttransplant. One patient experienced the accelerated rejection, resulting in the resection of the pancreas and kidney grafts because of the failure of conservative therapy. The incidence of the first rejection episodes at 3 months was 47.1% (8/17). Only the kidney was involved in 35.3% (6/17); and both the pancreas and kidney were involved in 11.8% (2/17). All these patients received a high-dose pulse of methylprednisone (0.5 g·d-1) for 3 days. OKT3 (0.5 mg·d-1) was administered for 7-10 days in two patients with both renal and pancreas rejection. All the grafts were successfully rescued. Conclusion Rejection, particularly acute rejection, is the major cause influencing graft function in SPK transplantation. Monitoring renal function and pancreas exocrine secretion, and reasonable application of immunosuppressants play im- portant roles in the diagnosis and treatment of rejection.

Exocrine drainage in vascularized pancreas transplantation in the new millennium

The history of vascularized pancreas transplantation largely parallels developments in immunosuppression and technical refinements in transplant surgery. From the late-1980 s to 1995, most pancreas transplants were whole organ pancreatic grafts with insulin delivery to the iliac vein and diversion of the pancreatic ductal secretions to the urinary bladder(systemic-bladder technique). The advent of bladder drainage revolutionized the safety and improved the success of pancreas transplantation. However, starting in 1995, a seismic change occurred from bladder to bowel exocrine drainage coincident with improvements in immunosuppression, preservation techniques, diagnostic monitoring, general medical care, and the success and frequency of enteric conversion. In the new millennium, pancreas transplants are performed predominantly as pancreatico-duodenal grafts with enteric diversion of the pancreatic ductal secretions coupled with iliac vein provision of insulin(systemic-enteric technique) although the systemic-bladder technique endures as a preferred alternative in selected cases. In the early 1990 s, a novel technique of venous drainage into the superior mesenteric vein combined with bowel exocrine diversion(portal-enteric technique) was designed and subsequently refined over the next ≥ 20 years to recreate the natural physiology of the pancreas with firstpass hepatic processing of insulin. Enteric drainage usually refers to jejunal or ileal diversion of the exocrine secretions either with a primary enteric anastomosis or with an additional Roux limb. The portal-enteric technique has spawned a number of newer and revisited techniques of enteric exocrine drainage including duodenal or gastric diversion. Reports in the literature suggest no differences in pancreas transplant outcomes irrespective of type of either venous or exocrine diversion. The purpose of this review is to examine theliterature on exocrine drainage in the new millennium(the purported "enteric drainage" era) with special attention to technical variations and nuances in vascularized pancreas transplantation that have been proposed and studied in this time period.

Pancreas transplantation in type Ⅱ diabetes mellitus

Although the diagnosis of type 2 diabetes mellitus was once considered a contraindication to simultaneous pancreas-kidney transplantation, a growing body of evidence has revealed that similar graft and patient survival can be achieved when compared to type 1 diabetes mellitus recipients. A cautious strategy regarding candidate selection may limit appropriate candidates from additional benefits in terms of quality of life and potential amelioration of secondary side effects of the disease process. Although our current understanding of the disease has changed, uniform listing characteristics to better define and study this population have limited available data and must be established.

Changes of inducible protein-10 and regulated upon activation, normal T cell expressed and secreted protein in acute rejection of pancreas transplantation in rats

瞄准：调查 IFN-gamma 可诱导的蛋白质 -10 (IP-10 ) 的角色并且在激活之上调整了，表示并且藏匿的正常 T 房间(RANTES ) 在在老鼠的尖锐胰腺的紧密相联的接枝拒绝的蛋白质。方法：一个试验性的胰移植模型作为接受者用糖尿病的 SD 老鼠被建立，由使用 streptozocin (STZ ) 导致了。胰移植与静脉的门和伤寒排水的一个生理的方法被执行。老鼠被划分成二个组，同基因移植物组(组 A， n = 24 ) 并且紧密相联的接枝组(组 B， n = 24 ) 在哪个也健康的 SD 老鼠或 Wistar 老鼠分别地用作施主。12 只糖尿病或健康的 SD 老鼠被用作控制。在 d， 1， 4， 7，和 10 柱子移植，浆液 IP-10 和 RANTES 被 ELISA 估计，他们在紧密相联的接枝的表示被免疫组织化学决定。结果：在组 B (紧密相联的接枝组) ，尖锐拒绝的开发显著地与增加的浆液集中和 IP-10 和 RANTES 的织物表示被相关，与在 d 的山峰水平 7 帖子移植。相反，在在组 A (同基因移植物组) 的移植前后没有明显的变化。结论：我们的学习建议在尖锐拒绝并且 chemokines 的早监视的 IP-10 和 RANTES 的一个可能的角色可能在预言胰移植的结果是有用的。

Protective effect of inducible nitric oxide synthase inhibitor on pancreas transplantation in rats

AIM: To investigate the effect of inducible nitric oxide synthase inhibitor, aminoguanidine, on pancreas transplantation in rats. METHODS: A model of pancreas transplantation was established in rats. Streptozotocin-induced diabetic male Wistar rats were randomly assigned to sham-operation control group (n= 6), transplant control group (n= 6), and aminoguanidine (AG) treatment group (n=18). In the AG group, aminoguanidine was added to intravascular infusion as the onset of reperfusion at the dose of 60 mg/kg, 80 mg/kg, 100 mg/kg body weight, respectively. Serum nitric oxide (NO) level, blood sugar and amylase activity were detected. Nitric oxide synthase (NOS) test kit was used to detect the pancreas cNOS and inducible NOS (iNOS) activity. Pancreas sections stained with HE and immunohistochemistry were evaluated under a light microscope. RESULTS: As compared with the transplant control group, the serum NO level and amylase activity decreased obviously and the evidence for pancreas injury was much less in the AG group. The AG (80 mg/kg body weight) group showed the most signifi cant difference in NO and amylase (NO: 66.0 ± 16.6 vs 192.3 ± 60.0, P < 0.01 and amylase: 1426 ± 177 vs 4477 ± 630, P < 0.01). The expression and activity of tissue iNOS, and blood sugar in the AG (80 mg/kg body weight) group were much lower than those in the transplant control group (iNOS: 2.01 ± 0.23 vs 26.59 ± 5.78, P < 0.01 and blood sugar: 14.2 ± 0.9 vs 16.8 ± 1.1, P < 0.01). CONCLUSION: Selective iNOS inhibitor, aminoguanidine as a free radical, has a protective effect on pancreas transplantation in rats by inhibiting NO and reducing its toxicity.

Simultaneous liver, pancreas-duodenum and kidney transplantation in a patient with hepatitis B cirrhosis, uremia and insulin dependent diabetes mellitus

Simultaneous liver,pancreas-duodenum,and kidney transplantation has been rarely reported in the literature. Here we present a new and more efficient en bloc technique that combines classic orthotopic liver and pancreas-duodenum transplantation and heterotopic kidney transplantation for a male patient aged 44 years who had hepatitis B related cirrhosis,renal failure,and insulin dependent diabetes mellitus(IDDM). A quadruple immunosuppressive regimen including induction with basiliximab and maintenance therapy with tacrolimus,mycophenolate mofetil,and steroids was used in the early stage post-transplant. Postoperative recovery was uneventful and the patient was discharged on the 15 th postoperative day with normal liver and kidney function. The insulin treatment was completely withdrawn 3 wk after operation,and the blood glucose level remained normal. The case findings support that abdominal organ cluster and kidney transplantation is an effective method for the treatment of end-stage liver disease combined with uremia and IDDM.

Two-layer cold storage method for pancreas and islet cell transplantation

The two-layer cold storage method (TLM) was f irst reported in 1988, consisting of a perfluorochemical (PFC) and initially Euro-Collins' solution, which was later replaced by University of Wisconsin solution (UW). PFC is a biologically inert liquid and acts as an oxygen-supplying agent. A pancreas preserved using the TLM is oxygenated through the PFC and substrates are supplied by the UW solution. This allows the pancreas preserved using the TLM to generate adenosine triphosphate during storage, prolonging the preservation time. In a canine model, the TLM was shown to repair and resuscitate warm ischemically damaged pancreata during preservation, improve pancreas graft survival after transplantation, and also improve the islet yield after isolation. Clinical trials using the TLM in pancreas preservation before whole-pancreas transplantation and islet isolation have shown promising outcomes. We describe the role of the TLM in pancreas and islet transplantation.

Pancreas transplantation: The Wake Forest experience in the new millennium

AIM: To investigate the Wake Forest experience with pancreas transplantation in the new millennium with attention to surgical techniques and immunosuppression. METHODS: A monocentric, retrospective review of outcomes in simultaneous kidney-pancreas transplant(SKPT) and solitary pancreas transplant(SPT) recipients was performed. All patients underwent pancreas transplantation as intent-to-treat with portal venous and enteric exocrine drainage and received depleting antibody induction; maintenance therapy included tapered steroids or early steroid elimination with my-cophenolate and tacrolimus. Recipient selection was based on clinical judgment whether or not the patient exhibited measureable levels of C-peptide. RESULTS: Over an 11.25 year period, 202 pancreas transplants were performed in 192 patients including 162 SKPTs and 40 SPTs. A total of 186(92%) were primary and 16(8%) pancreas retransplants; portalenteric drainage was performed in 179 cases. A total of 39 pancreas transplants were performed in African American(AA) patients; of the 162 SKPTs, 30 were performed in patients with pretransplant C-peptide levels > 2.0 ng/m L. In addition, from 2005-2008, 46 SKPT patients were enrolled in a prospective study of single dose alemtuzumab vs 3-5 doses of rabbit antithymocyte globulin induction therapy. With a mean follow-up of 5.7 in SKPT vs 7.7 years in SPT recipients, overall patient(86% SKPT vs 87% SPT) and kidney(74% SKPT vs 80% SPT) graft survival rates as well as insulin-free rates(both 65%) were similar(P = NS). Although mortality rates were nearly identical in SKPT compared to SPT recipients, patterns and timing of death were different as no early mortality occurred in SPT recipients whereas the rates of mortality following SKPT were 4%, 9% and 12%, at 1-, 3- and 5-years follow-up, respectively(P < 0.05). The primary cause of graft loss in SKPT recipients was death with a functioning graft whereas the major cause of graft loss following SPT was acute and chronic rejection. The overall incidence of acute rejection was 29% in SKPT and 27.5% in SPT recipients(P = NS). Lower rates of acute rejection and major infection were evidenced in SKPT patients receiving alemtuzumab induction therapy. Comparable kidney and pancreas graft survival rates were observed in AA and non-AA recipients despite a higher prevalence of a "type 2 diabetes" phenotype in AA. Results comparable to those achieved in insulinopenic diabetics were found in the transplantation of type 2 diabetics with detectable C-peptide levels.CONCLUSION: In the new millennium, acceptablemedium-term outcomes can be achieved in SKPT and SPTs as nearly 2/3rds of patients are insulin independent following pancreas transplantation.

Pancreas transplantation in the mouse

BACKGROUND: Pancreas transplantation is the only established treatment to achieve long-term normoglycemia and insulin independence in patients with insulin-dependent diabetes mellitus. However, many complications both during and post-transplantation have limited the progress of pancreas transplantation. Mice are the widely used laboratory animals that have been used to establish pancreas transplant models. The pathogenesis and the treatment of pancreas allograft rejection have been studied during the last twenty years. This review introduces four different mouse pancreas transplantation models established by different centers. DATA SOURCES: We reviewed the three mostly reported mouse pancreas transplantation models in the literature (Pub Med), and compared them with a novel mouse model established at our center. RESULTS: In this review, four different models of mouse pancreas transplantation were compared in terms of surgical technique, immediate success rate, advantages and disadvantages. CONCLUSIONS: The mouse model is a useful tool to study pancreas transplantation-related diseases and their treatment. The findings from this model help to improve human pancreas transplantation in the future. (Hepatobilinty Pancreat Dis Int 2010; 9:254-258)

The Current State of Pancreas-kidney Transplantation in China:The Indications,Surgical Techniques and Outcome

It is currently estimated that 50 million Chinese have diabetic mellitus （DM） with more than 90% of these being afflicted with type 2 DM. Concomitantly, the socio-economic improvements in China are supporting the adoption of pancreas-kidney transplantations as a treatment option for these patients. Recipient candidate pool has yet to be expanded and the final effect to be improved in clinical practice. To date, more than 250 pancreas-kidney transplants have been performed on patients with type 1 and type 2 DM. To improve the outcome, a new surgical technique that involves anastomosis of the graft duodenum to recipient jejunum side-to-side but not Roux-en-Y, has been devised for enteric drainage. Furthermore, the systemic venous drainage （SVD） has been used as the method of choice for endocrine secretions. Graft and recipient long-term survival in China was similar to that in America and Europe. Three-year survival rate of pancreas and kidney grafts was 92.2% and 90.2%, respectively, in our center. No difference in survival and graft function between type 1 and type 2 DM recipients was noted. It is concluded that pancreas-kidney transplantation is an effective way for the treatment of type 1 DM and some type 2 DM complicated with uremia.

Studies of CTLA4Ig in acute rejection of pancreas transplantation in rats

Objective： To investigate the protective effect of CTLA4Ig in rejection of pancreaticoduodenal transplantation model of rat. Methods ： Pancreaticoduodenal transplantion models were established from the donor F344 rats to the Lewis recipients. The models were divided into 2 groups： Group A and B with 12 rats in each group.2 days after transplantation, reciepients in group A were treated with i.p. injection of sailine, and those in group B CTLA41 were injected（200μg）. On day 1,4,7, 10 after transplantation, the grafts were harvested for histopathological examination. On day 4 after transplantation, the CD4^＋CD25^＋ T cells in the grafts were detected by Flow Cytometry. Results： Compared with group A： the degree of the rejection of grafts in group B was lower. The number of CD4^CD25^＋ T cells of graft was （7.91±1.26）% in group A and （13.81±1.71）% in group B, which had significant difference （P〈0.01）. Conclusion： CTLA4Ig could inhibit T cell costimulatory pathway, prevent acute rejection, which might be mediated bv increasing the number of CD4^＋CD25^＋ regulatory T cells.

Anatomical basis for pancreas transplantation via isolated splenic artery perfusion:A literature review

The variability of vascular anatomy of the pancreas underlines the difficulty of its transplantation.Research regarding the consistency of anatomical variations shows splenic arterial dominance in most cases.This can significantly improve transplantation success.A systematic literature review was performed according to the quality standards described in the AMSTAR measurement tool and the PRISMA guidelines.We valuated existing literature regarding the vascularization and blood perfusion patterns of the pancreas in terms of dominance and variability.The collected data was independently analyzed by two researchers.Variance of vascular anatomy was seen to be underreported in literature,though significant findings have been included and discussed in this study,providing valuable insight into the dynamics of pancreatic perfusion and feasibility of transplantation on several different supplying arteries.The splenic artery(SA)has a high percentage of consistency in all found studies(over 90%).High frequency of anastomoses between arterial pools supplying the pancreas can mediate sufficient blood supply through a dominant vessel,such as the SA,which is present in most cases.Pancreatic transplantation with isolated SA blood supply can provide sufficient arterial perfusion of the pancreas for stable transplant viability due to high anatomical consistency of the SA and vast communications with other arterial systems.