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.

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.

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.

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

AIM： To investigate the role of IFN-T inducible protein -10 （IP-10） and regulated upon activation, normal T cell expressed and secreted （RANTES） protein in acute pancreatic allograft rejection in rats. METHODS： An experimental model was established using pancreas transplantation diabetic SD rats as the recipient, induced by applying streptozocin （STZ）. Pancreas transplantation was performed with a physiologic method of portal venous and enteric drainage. Rats were divided into two groups, isograft group （group A, n = 24） and allograft group （group B, n = 24） in which either healthy SD rats or Wistar rats served as donors, respectively. Twelve diabetic or healthy SD rats were used as controls. At d 1, 4, 7, and 10 post transplantation, serum IP-10 and RANTES were assessed by ELISA and their expression in the allografts was determined by immunohistochemistry. RESULTS： In group B （allograft group）, the development of acute rejection was significantly correlated with increased serum concentration and tissue expression of IP-10 and RANTES, with a peak level at d 7 post transplantation. In contrast, there was no obvious change before and after transplantation in group A （isograft group）. CONCLUSION： Our study suggests a possible role of IP-10 and RANTES in acute rejection and early monitoring of chemokines may be helpful in predicting the outcome of pancreas transplantation.

Donor risk factors in pancreas transplantation

The aim of the work was to analyze and expose the donor and recipient riskfactors in pancreas transplantation. In the following paper, we exposed the 2018Spanish Consensus Document on Donor and Recipient Selection Criteria forPancreas Transplantation. An assessment of the previous Selection Criteria forDonors and Recipients of Pancreas Transplantation, published in 2005 by theSpanish Pancreas Transplant Group (GETP) and the National TransplantOrganization (ONT) was performed. A literature review was performed usingCochrane Library, PubMed and Google Scholar databases. Some of the followingterms were used for the literature search: “Diabetes Mellitus,” “PancreasTransplantation,” “Insulin-Secreting Cells,” “Pancreas Allograft Thrombosis,”“Allograft Pancreatitis,” “Donors’ Risk Factors,” “Recipients’ Risk Factors,”“Pancreas Allograft Rejection” and “Pancreas Allograft Survival.” After anextended search, different inclusion criteria were established. Articles anddocuments with abstracts of full text and in English or Spanish language wereselected. Subsequently, different scientific meetings took place during 2015 and2016 by the GETP. Finally, the updated criteria were published by the GETP andONT in 2018. Several risk factors have been described in pancreas transplantationthat can be divided into donor risk factors: Advanced age (> 50 years);high bodymass index (BMI) (> 30 kg/m2);cause of death (e.g., stroke);previoushyperglycemia;hyperamylasemia;cold ischemia time (greater than 8 or 12 h,depending on the type of donation);the use of vasopressors in the intensive careunit or cardiac arrest;and the macroscopic aspect of the pancreas allograft. Thefollowing are recipient risk factors: Advanced age (> 50 years);active smoking;high BMI (> 30 kg/m2);and peripheral artery disease or sensorimotorpolyneuropathy. Based on the aforementioned parameters, different selectioncriteria have been established for the recipients depending on the type of pancreastransplantation. Knowledge of the risk factors for pancreas transplantation allowsthe establishment of reliable selection criteria for choosing donors and recipients.

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.

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)

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.

Challenges of pancreas transplantation in developing countries,exploring the Turkey example

Pancreas transplantation significantly improves the quality of life for people with type 1 diabetes,primarily by eliminating the need for insulin and frequent blood glucose measurements.Despite the growing numbers of solid organ transplantations worldwide,number of pancreas transplantations in the developing countries`remain significantly low.This difference of pancreas transplantation practices was striking among the participating countries at the 1st International Transplant Network Meeting which was held in Turkey on 2018.In this meeting more than 40 countries were represented.Most of these counties were developing countries located in Africa,Middle East or Asia.The aim of this article is to identify the challenges and limiting factors for pancreas transplantations in these developing countries,by exploring the Turkish example.The challenges faced by the developing countries are broadly classified in four categories;wait-listing,donor pool,team work and follow up.Under these categorical titles,issues are further discussed in detail,giving examples from Turkish practice of pancreas transplantation.Additionally,several solutions to these challenges have been proposed-some of which have already been undertaken by the Turkish Ministry of Health.With the insight and methods presented in this article,pancreas transplantation should be made possible for the potential recipients in the developing countries.

Predicting early graft loss in pancreas transplantation using novel imaging techniques: are we there yet?

Since its inception in 1966 at the University of Minnesota,pancreas transplantation has witnessed major milestones in evolution of surgical techniques,immunosuppression regimen and more recently,machine perfusion for optimising graft utilisation(1).

Meningeal cryptococcosis in a pancreas transplant recipient requiring grafectomy: A case report

BACKGROUND Through continuous improvement in transplantation medicine,a wider range of solid organ transplant(SOT)recipients is considered suitable for complex procedures.Despite advances in modern transplantation practice,transpiring invasive fungal infections pose a substantial threat for SOT recipients.To our knowledge,cryptococcal infection confined amidst sole pancreas SOT recipients has not been described to date.Enforcement of a multidisciplinary transplant team approach in the management of pancreas SOT recipients presenting with complex cryptococcal complications is fundamental in improving patient outcomes.CASE SUMMARY We present the case of a female pancreas transplant recipient,with confirmed meningeal cryptococcosis,referred to our institution for further evaluation and treatment from the Regional Center for Infectious Diseases.On admission,the patient was weaned from the protocolized immunosuppression therapy for two consecutive weeks,in addition to tapering systemic corticosteroid remedial treatment.Our novel multidisciplinary transplant team approach embodied exhaustive discussions of possible complex and diverse multiple organ system physiologic and pathologic challenges associated with distinct management strategies in pancreas transplant recipients.Owing to the potentially devastating impact of invasive cryptococcosis in terms of morbidity and mortality,a definitive surgical intervention of pancreas transplant grafectomy was reinforced,as a pathway towards secure access to early meaningful expertise care.The patient was discharged to the Regional Center for Infectious Diseases 2 mo after the admittance further advancing to a clinical improvement.CONCLUSION The precision transplantation approach by tailoring complex medical interventions to individual needs proved indispensable in improving our patient’s outcomes.

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.

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.

Surgical complications after pancreatic transplantation:A computed tomography imaging pictorial review

Pancreatic transplantation is considered by the American Diabetes Association and the European Association for the Study of Diabetes an acceptable surgical procedure in patients with type 1 diabetes also undergoing kidney transplantation in pre-final or end-stage renal disease if no contraindications are present.Pancreatic transplantation,however,is a complex surgical procedure and may lead to a range of postoperative complications that can significantly impact graft function and patient outcomes.Postoperative computed tomography(CT)is often adopted to evaluate perfusion of the transplanted pancreas,identify complications and as a guide for interventional radiology procedures.CT assessment after pancreatic transplantation should start with the evaluation of the arterial Y-graft,the venous anastomosis and the duodenojejunostomy.With regard to complications,CT allows for the identification of vascular complications,such as thrombosis or stenosis of blood vessels supplying the graft,the detection of pancreatic fluid collections,including pseudocysts,abscesses,or leaks,the assessment of bowel complications(anastomotic leaks,ileus or obstruction),and the identification of bleeding.The aim of this pictorial review is to illustrate CT findings of surgical-related complications after pancreatic transplantation.The knowledge of surgical techniques is of key importance to understand postoperative anatomic changes and imaging evaluation.Therefore,we first provide a short summary of the main techniques of pancreatic transplantation.Then,we provide a practical imaging approach to pancreatic transplantation and its complications providing tips and tricks for the prompt imaging diagnosis on CT.

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.

Back-table surgery pancreas allograft for transplantation:Implications in complications

To describe the main aspects of back-table surgery in pancreatic graft and the problems arising from poor technique.Back-table surgery for pancreatic graft is a complex,meticulous and laborious technique on which the success of implant surgery and perioperative results depends.The technique can be described in the following steps:Preparation of the sterile table,ex-situ inspection of the pancreasspleen block,management of the duodenum,identification of the bile duct,preparation of the portal vein,preparation of the own graft arteries and anastomosis to the arterial graft,spleen management and graft preservation prior to implantation in the recipient.A careful inspection of the pancreas-spleen block should be performed.It is important to identify the stump of the main bile duct,the portal vein cuff,and the arrangement of the superior mesenteric artery and splenic artery.The redundant duodenum must be removed.The availability of a good venous cuff facilitates the portal vein anastomosis and the positioning of the graft,two key points to prevent thrombosis.The section line of the arteries must be clean,without atherosclerosis,to prevent arterial thrombosis.The superior and splenic mesenteric arteries are generally separated by dense fibrolymphatic tissue.The artery can be reconstructed by interposing a"Y"graft from the donor iliac artery;or with an end-to-end anastomosis between the splenic artery and the superior mesenteric artery.An exquisite technique of bench work helps to prevent the most feared complications of pancreas transplantation:Thrombosis and graft pancreatitis.

DIFFERENCE OF REJECTION IN SINGLE VERSUS COMBINED PANCREAS AND KIDNEY TRANSPLANTATION IN RATS

Objective.To investigate the difference of rejection in single versus combined pancreas and kidney transplantation in rats. Methods.Allograft models including simultaneous pancreas and kidney(SPK)transplant and pancreas or kidney transplant alone were established in SD-Wistar rats, rejections of pancreas and kidney in different models were compared morphologically and functionally. Results.Mean survival time(MST)of pancreas was significantly prolonged in SPK than in pancreas transplant alone(PTA)(115 days vs. 92 days, P<005). Incidence of interstitial pancreatic rejection at grade Ⅱ and grade Ⅲ was much obvious in PTA than in SPK(429% vs. 125% at grade Ⅱ and 286% vs 63% at grade Ⅲ , P<005). No significant difference was found in MST between SPK and kidney transplant alone(KTA). Administration of cyclosporine A prolonged the MST of pancreas and kidney, without altering the tendency stated above. Conclusions.In SPK, the function of pancreas is protected by kidney hence the severity of rejection is reduced, whereas the function of kidney is not protected by pancreas. It suggests that different organs differ in immunoallergization and immunoregulation, and immune response tend to attack organs with greater immunoactivity, those organs with minor one could be protected. Cyclosporine A is effective on prolonging the MST of pancreas and kidney.

Establishment of simultaneous pancreas and kidney transplantation (SPK) model with cuff technique and portal venous drainage in rats

To establish a simultaneous pancreas and kidney transplantation （SPK） model in the rat. Methods： SD rats served as donors and recipients. The donor portal vein and the recipient superior mesenteric vein were anastomosed and the donor renal veins and recipient renal veins were anastomosed by cuff method. Arterial reconstruction was carried out by end to side anastomosis of the donor abdominal aorta to the recipient abdominal aorta. Enteric drainage was performed by side to side anastomosis between donors＇ duodenum and recipients＇ jejunum. The donor ureter -bladder valve was anastomosed to the bladder of recipients. Results： Out of 30 cases of SPK transplantation, 24 had normal serum glucose and serum creatinine after operation. The successful rate was 80 %. Conclusion： This model of SPK in rats is stable and reliable, which could be applied for further scientific research.

Mortality assessment for pancreas transplants in the United States over the decade 2008-2018

BACKGROUND Pancreas transplant is the only treatment that establishes normal glucose levels for patients diagnosed with diabetes.However,since 2005,no comprehensive analysis has compared survival outcomes of:(1)Simultaneous pancreas-kidney(SPK)transplant;(2)Pancreas after kidney(PAK)transplant;and(3)Pancreas transplant alone(PTA)to waitlist survival.AIM To explore the outcomes of pancreas transplants in the United States during the decade 2008-2018.METHODS Our study utilized the United Network for Organ Sharing Standard Transplant Analysis and Research file.Pre-and post-transplant recipient and waitlist characteristics and the most recent recipient transplant and mortality status were used.We included all patients with type I diabetes listed for pancreas or kidneypancreas transplant between May 31,2008 and May 31,2018.Patients were grouped into one of three transplant types:SPK,PAK,or PTA.RESULTS The adjusted Cox proportional hazards models comparing survival between transplanted and non-transplanted patients in each transplant type group showed that patients who underwent an SPK transplant exhibited a significantly reduced hazard of mortality[hazard ratio(HR)=0.21,95%confidence intervals(CI):0.19-0.25]compared to those not transplanted.Neither PAK transplanted patients(HR=1.68,95%CI:0.99-2.87)nor PTA patients(HR=1.01,95%CI:0.53-1.95)experienced significantly different hazards of mortality compared to patients who did not receive a transplant.CONCLUSION When assessing each of the three transplant types,only SPK transplant offered a survival advantage compared to patients on the waiting list.PKA and PTA transplanted patients demonstrated no significant differences compared to patients who did not receive a transplant.

Protective effects of L-arginine on reperfusion injury after pancreaticoduodenal transplantation in rats

BACKGROUND: Post-transplantation pancreatitis andgraft thrombosis are two major complications of pancreastrans-plantation that contribute to morbidity, mortality, andgraft loss. Nitric oxide (NO) is a potent vasodilator agentformed when L-arginine ( L-Arg) is converted to L-citrul-line by the action of NO synthase (NOS), and plays a ma-jor role in microcirculatory changes. We therefore investi-gated the effect of L-Arg on reperfusion injury followingpancreaticoduodenal transplantation in rats.METHODS: The homologous male Wistar rat model ofheterotopic total pancreaticoduodenal transplantation wasused. The L-Arg-treated rats received the intravenous in-jection of L-Arg 5 minutes before and after reperfusion at adose of 200 mg/kg while the N-Nitro-L-arginine methyl es-ter (L-NAME) -treated rats at a dose of 10 mg/kg. Theamount of NO in the pancreas graft was measured. Serumconcentration of cytokine-induced neutrophil chemoattrac-tant ( CINC) was determined by enzyme-linked immu-nosorbant assay, the expression of CINC mRNA was detect-ed by Northern blot assay in the pancreas graft, and the ac-tivity of myeloperoxidase (MPO) was measured. Histolo-gical examination was performed.RESULTS: The amount of NO was higher in the L-Arggroup than in the control group, while it was lower in theL-NAME group than in the control group (P <0.05). Thepeak of serum CINC concentration occurred 3 hours afterreperfusion with the difference among the groups being sig-nificant. The expression peak of CINC mRNA in the pan-creas graft occurred 3 hours after reperfusion. The expres-sion level in the L-Arg group (7.66 ± 1.53 μg/L) was lowerthan in the control group (26.31±2.01 μg/L), while in theL-NAME group (34.18 ±3.12 μg/L) it was higher than thatin the control group (P <0. 05). The activity of MPO inthe L-Arg group was obviously decreasd as compared within the other groups. The pancreas inflammation was ame-liorated when L-Arg was administered, whereas the panc-reas damage was aggravated when L-NAME was adminis-tered.CONCLUSIONS: L-Arg can increase the amount of NOand inhibit the elevation of CINC, the CINC mRNA ex-pression and early neutrophil accumulation in the pancreas.NO has protective effects on ischemia/reperfusion injury inpancreaticoduodenal transplantation.