Effect of the surgical technique on long-term outcome of pancreas transplantation

To date there is no general consensus as to the best surgical technique for pancreas transplantation. Patients with a pancreas transplant functioning for 3 years or more were retrospectively investigated to compare three surgical techniques: segmental graft with duct obstruction (DO), whole graft with bladder drainage (BD), and whole graft with enteric drainage (ED). Several parameters were studied: patient and graft survival, rejection, long-term surgical and medical complications, and endocrine function. The best results in terms of graft survival and quality of metabolic control were obtained in the group that underwent whole graft transplantation with ED. At 3 years, overall pancreas graft survival was 65 % for ED, 60 % for BD, and 47 % for DO. This surgical method has become the preferred technique in our unit. Received: 9 October 1997 Received after revision: 29 January 1998 Accepted: 30 March 1998     

Vessel rejection secondary to human leucocyte antigen antibodies directed against the arterial conduit following pancreas transplantation from a separate donor

Whole‐organ pancreas transplantation is typically carried out using a Y‐graft derived from the donor iliac vessels. We describe a case in which a 31‐year‐old male underwent a simultaneous pancreas‐kidney transplant, but in which vessels from a different donor were used for the arterial anastomosis of the pancreas graft. Although initially there was good function, 18 months post‐transplant the patient was admitted with diabetic ketoacidosis secondary to pancreas graft failure. Radiological investigations revealed complete occlusion of the vascular Y‐graft, and laboratory investigations demonstrated donor‐specific human leucocyte antigen (HLA) antibodies directed against HLA mismatches of the vessel donor. This case highlights the risks of using allogeneic vascular material for surgical anastomoses.     

Pancreas‐After‐Islet Transplantation in Nonuremic Type 1 Diabetes: A Strategy for Restoring Durable Insulin Independence

Islet transplantation offers a minimally invasive approach for β cell replacement in diabetic patients with hypoglycemic unawareness. Attempts at insulin independence may require multiple islet reinfusions from distinct donors, increasing the risk of allogeneic sensitization. Currently, solid organ pancreas transplant is the only remaining surgical option following failed islet transplantation in the United States; however, the immunologic impact of repeated exposure to donor antigens on subsequent pancreas transplantation is unclear. We describe a case series of seven patients undergoing solid organ pancreas transplant following islet graft failure with long‐term follow‐up of pancreatic graft survival and renal function. Despite highly variable panel reactive antibody levels prior to pancreas transplant (mean 27 ± 35%), all seven patients achieved stable and durable insulin independence with a mean follow‐up of 6.7 years. Mean hemoglobin A1c values improved significantly from postislet, prepancreas levels (mean 8.1 ± 1.5%) to postpancreas levels (mean 5.3 ± 0.1%; p = 0.0022). Three patients experienced acute rejection episodes that were successfully managed with thymoglobulin and methylprednisolone, and none of these preuremic type 1 diabetic recipients developed stage 4 or 5 chronic kidney disease postoperatively. These results support pancreas‐after‐islet transplantation with aggressive immunosuppression and protocol biopsies as a viable strategy to restore insulin independence after islet graft failure.     

Successful surgical salvage of pancreas allograft

BACKGROUND: Early and late complications related to the pancreas after simultaneous kidney-pancreas transplantation (SKPT) frequently result in graft loss. The authors describe a surgical rescue technique that allows salvage of the pancreatic graft when surgical complications appear after the transplant. METHODS: Of 158 patients who underwent SKPT, 7 were identified with posttransplant complications that required surgical salvage of the pancreas allograft. The surgical salvage technique consisted of the following: pancreatoduodenectomy with conversion from whole-pancreas transplant with bladder or enteric diversion to segmental graft with duct injection (three cases) and conversion from whole-pancreas transplant with duct injection (four cases). RESULTS: Five of seven pancreas allografts are still functioning, with a mean follow-up of 28 months (range, 6-42 months). CONCLUSION: The described surgical treatment may be useful for surgical salvage of the pancreatic allograft, without major impairment of endocrine function.     

Preservation of the donor pancreas for whole pancreas and islet transplantation

Ridgway D, Manas D, Shaw J, White S. Preservation of the donor pancreas for whole pancreas and islet transplantation.
Clin Transplant 2010: 24: 1–19. © 2009 John Wiley & Sons A/S.
Abstract:  Whole pancreas and islet cell transplantation are both reliant upon the procurement and preservation of a high quality donor pancreas for a successful outcome. In the climate of a reducing donor pool it is imperative that donor optimization, meticulous surgical retrieval and evidence based methods of preservation are practiced to ensure optimal graft quality. Moreover expanded criteria donors and novel methods of pancreas preservation have the potential to expand the number of usable grafts and increase the availability of these transplant modalities to suitable patients with diabetes. This article provides a review of the current literature surrounding donor management, surgical technique and the various technologies of organ preservation applicable to the donor pancreas.     

Transplantation with pancreas after living donor kidney vs. living donor kidney alone in type 1 diabetes mellitus recipients*

Sampaio MS, Poommipanit N, Cho YW, Shah T, Bunnapradist S. Transplantation with pancreas after living donor kidney vs. living donor kidney alone in type 1 diabetes mellitus recipients.
Clin Transplant 2010: 24: 812–820. © 2009 John Wiley & Sons A/S. Abstract: Living donor kidney transplantation (LDKT) in type 1 diabetic recipients (T1DM) may be followed by a pancreas after living donor kidney (PALK). The impact of the PALK is largely unknown. Adult T1DM living donor kidney recipients (1997–2007) listed for pancreas transplantation were divided into those who subsequently received pancreas transplantation and those who did not (living donor kidney transplant alone [LDKA]). Outcomes were compared. A sub‐analysis was performed in recipients with at least one yr of kidney graft survival and limiting PALK to those who underwent pancreas transplantation in the first year. Of 4554 recipients, 23% received PALK. PALK had more favorable baseline characteristics. At the end of eight yr, we found significantly superior patient (85% vs. 75%) and kidney graft survival (75% vs. 62%) in PALK group. The adjusted hazard ratios of PALK (LDKA as reference) were 0.65 (95%CI: 0.52–0.81) for death and 0.63 (0.54–0.76) for renal graft loss. In sub‐group analysis, there was a trend toward decreased death in PALK (HR = 0.78: 0.57–1.07). In conclusion, only 23% of those wait‐listed received a pancreas with patient and kidney survival superior to LDKA. Pancreas transplant in the first year after kidney transplant was associated with a trend toward better long‐term patient survival.     

Pre-clinical model of composite foetal pig pancreas fragment/renal xenotransplantation to treat renal failure and diabetes

Hawthorne WJ, Simond DM, Stokes R, Patel AT, Walters S, Burgess J, O’Connell PJ. Pre‐clinical model of composite foetal pig pancreas fragment/renal xenotransplantation to treat renal failure and diabetes. Xenotransplantation 2011; 18: 390–399. © 2011 John Wiley & Sons A/S. Abstract: Background: Development of a limitless source of β cells for xenotransplantation into patients suffering type 1 diabetes and renal failure that can control their diabetes and provide normal renal function in one procedure would be a major achievement. For the islet tissue to survive transplantation, as an islet‐kidney composite graft this would have significant advantages. It would simplify the surgical procedure; remove the complications caused by the exocrine pancreas whilst reversing diabetes and uraemia. It was our hypothesis that a composite foetal porcine pancreas fragment (FPPF)/renal graft could achieve these objectives in a large pre‐clinical animal model as a means to establish whether this would be feasible before moving to the clinic. Methods: Inbred ‘Westran’ pig FPPF were transplanted under the kidney capsule of syngeneic Westran pig recipients without immunosuppression. Following maturation of the FPPF under the renal subcapsular space of this recipient, this kidney bearing the composite FPPF piggyback graft was removed and transplanted into another nephrectomized and pancreatectomized recipient to demonstrate function. Results: Under the kidney capsule of the first transplant group (n = 6), the FPPF‐transplanted tissue developed and matured to form islet cell nests. These composite FPPF/renal grafts were then successfully removed and transplanted into the second functional assessment recipient group. This second group of six composite FPPF/renal‐grafted pigs had normal renal function for more than 44 days and normal glucose homoeostasis without exogenous insulin as assessed by normal glucose tolerance tests, K values and normal glucagon secretion. Histological analysis showed despite the ischaemic insult during the composite kidney transplant procedure, there was appropriate development of islet‐like structures up to and beyond 224 days after the original transplantation under the kidney capsule. Conclusions: This study shows that the use of composite FPPF/renal grafts can cure both diabetes and renal failure with a single‐transplant procedure. Using such composite grafts for xenotransplantation would simplify the surgical procedure and protect the islet graft from the immediate innate immune response.     

Retroperitoneal pancreas transplantation with systemic-enteric drainage--case report

Enteric drainage and intraperitoneal graft position is the preferred technique for pancreas transplantation at most transplant centers. The technique of retroperitoneal pancreas transplantation was first described by Boggi et al. [Transplantation,79 (2005), 1137]. In this case report, a modified model of retroperitoneal pancreas transplantation with systemic-enteric drainage is presented. A 48-yr-old patient underwent combined retroperitoneal pancreas and kidney transplantation because of type-I-diabetes, and diabetic nephropathy. At the time of transplantation, the patient had a body mass index of 31 and severe atherosclerosis of the iliac vessels. After mobilization of the colon and mesocolon ascendens, the vessels of the pancreas graft were anastomosed end-to-side to the aorta and to the inferior caval vein of the recipient. For exocrinous drainage, a side-to-side duodenojejunostomy was performed after bringing a jejunal loop through a window in the right colon mesentery. The graft was in a retroperitoneal position. The patient was insulin-independent after 48 h, the lipase and amylase levels were within the normal range. The first experience with retroperitoneal pancreas transplantation with systemic-enteric drainage showed that the technique was safe and had technical advantages when compared with the classic method.     

Pseudoaneurysm of the Y-graft/iliac artery anastomosis following pancreas transplantation: a case report and review of the literature

Transplant-related aneurysms are an unusual complication following pancreas transplantation. We present a case of a pseudoaneurysm developing in a recipient 6 months after bladder-drained pancreas transplantation. The pseudoaneurysm was incidentally found during ultrasonographic evaluation in preparation for a pancreas biopsy. Angiography demonstrated that the origin of the pseudoaneurysm was located near the base of the Y-graft/iliac artery anastomosis. Surgical repair was performed using standard vascular techniques. The patient subsequently recovered without loss of graft exocrine or endocrine function. Review of the literature revealed that aneurysms of various types associated with pancreas transplantation have a high incidence of graft loss and contribute significantly to patient morbidity. However, with prompt diagnostic and surgical management, non-infected pseudoaneurysms can be repaired without loss of pancreatic function.     

Effect of donor pancreas extraction time on pancreas transplantation—a Swiss tertiary center experience

We aimed to assess the effect of donor pancreas extraction time (ET) on postoperative complications and graft function after pancreas transplantation (PT). We analyzed all consecutive donor pancreas procurements for the simultaneous pancreas and kidney transplantation (SPK) and the associated PT in a Swiss transplant center over a 20-year period. Pancreas ET was defined as the time from cold flush to static storage of the pancreas on ice. The primary endpoint was the effect of extraction time on surgical complications. Secondary endpoints comprised the effect of ET on graft function (insulin-free survival) and graft pancreatitis. Of 115 procured pancreas grafts the median donor pancreas ET was 65 min (IQR: 48–78 min). In multivariable analysis, ET did not negatively affect major complications (OR 1.41 [95% CI: .59–3.36]; p = .438) and insulin-free survival (HR 1.42 [95% CI: .55–3.63]; p = .459). The median CIT was 522 (441–608) min. CIT was associated with major complications (OR 2.51 [95% CI: 1.11–5.68]; p = .027), but without impact on insulin-free survival (HR 1.94 [95% CI: .84–4.48]; p = .119). Patients with and without graft pancreatitis had no statistically significant differences in ET and CIT (p = .164 and p = .47, respectively). In multivariable analysis, Amylase levels > 270 U/L on postoperative day 1 were significantly associated with major complications (OR 3.61 [95% CI: 1.06–12.32]; p = .040). Our results suggest that although no effect of ET on complications and graft function after PT was found, shorter CIT and less graft pancreatitis can have a positive impact on surgical complications. Results could possibly be influenced by the exceptional quality of the pancreas donors, with short travel distances and preservation times in Switzerland.     

Pancreas After Islet Transplantation: A First Report of the International Pancreas Transplant Registry

Pancreas after islet (PAI) transplantation is a treatment option for patients seeking insulin independence through a whole‐organ transplant after a failed cellular transplant. This report from the International Pancreas Transplant Registry (IPTR) and the United Network for Organ Sharing (UNOS) studied PAI transplant outcomes over a 10‐year time period. Forty recipients of a failed alloislet transplant subsequently underwent pancreas transplant alone (50%), pancreas after previous kidney transplant (22.5%), or simultaneous pancreas and kidney (SPK) transplant (27.5%). Graft and patient survival rates were not statistically significantly different compared with matched primary pancreas transplants. Regardless of the recipient category, overall 1‐ and 5‐year PAI patient survival rates for all 40 cases were 97% and 83%, respectively; graft survival rates were 84% and 65%, respectively. A failed previous islet transplant had no negative impact on kidney graft survival in the SPK category: It was the same as for primary SPK transplants. According to this IPTR/UNOS analysis, a PAI transplant is a safe procedure with low recipient mortality, high graft‐function rates in both the short and long term and excellent kidney graft outcomes. Patients with a failed islet transplant should know about this alternative in their quest for insulin independence through transplantation.     

Prognostic risk factors for graft failure following pancreas transplantation: results of multivariate analysis of data from the International Pancreas Transplant Registry

Abstract. A multivariate analysis of prognostic factors for graft failure was performed on patients in the International Pancreas Transplant Registry. The analysis was restricted to the period January 1978 to June 1987 and included 764 patients. All patients had at least 1 year of follow-up. The following variables were studied: transplant year, continent (N. America, Europe, others), type of donor (cadaver, living related mismatched, living related HLA-identical), donor mismatch at the HLA A, B loci, donor mismatch at the DR loci, preservation time, kidney association (pancreas transplant alone, simultaneous pancreas and kidney transplant, pancreas after kidney transplant), whole versus segmental pancreatic transplant, graft duct management technique (polymer injection, enteric drainage, stomach drainage, bladder drainage), and immunosuppression. By stepwise, logistic regression analysis, we found that the following factors were predictive for 1-year graft function: donor mismatch at the DR loci ( P = 0. 0003), kidney association ( P < 0. 0001), type of donor ( P = 0. 04), and immunosuppression ( P = 0. 0002). For donor mismatch at the DR loci, we found an odds ratio for success of 2. 2 for 0 versus 2 mismatches. The odds for success were 2. 9 for simultaneous pancreas and kidney transplant versus pancreas transplant alone. The best results-79% 1-year graft survival-were obtained for the combination of 0 mismatches at the DR loci, pancreas after kidney transplant, living related HLA-identical donor, and the immunosuppressive regimen consisting of cyclosporin, azathioprine, and prednisone. Patients receiving a pancreas transplant alone with 0 mismatches at the DR loci, living related HLA-identical donor, and triple immunosuppressive regimen had a predicted 1-year graft survival of 71%.     

The unrecognized posterior gastric artery: a potential cause of surgical complications in pancreas transplantation

BACKGROUND: Our report describes, for the first time, a pre-transplant vascular complication in a pancreas graft related to the posterior gastric artery - a major, but relatively unknown side branch of the splenic artery. The posterior gastric artery that was overlooked by a surgical procurement team during donor pancreatectomy led to distortion of the peripancreatic vascular anatomy and set the stage for a splenic artery injury. METHODS: We identified the transected, partially resected graft splenic artery during backtable preparation of the pancreas, and repaired it using standard vascular surgical techniques. RESULTS: The recipient's post-operative course was uncomplicated. At 9-yr post-transplant, the recipient is alive with good pancreas graft function. CONCLUSIONS: The relevance of the posterior gastric artery with regard to general surgical procedures was only recently recognized. Our case demonstrates that the posterior gastric artery is also important in transplant surgery. Awareness of this anatomical structure during organ procurement would help minimize pre-transplant vascular complications.     

维拉帕米提高移植胰功能的研究

目的 :研究同种异体胰腺移植中应用维拉帕米提高移植胰的功能。方法 :将 2 0头健康小型猪 ,随机分成A、B两组 ,每组 10头 ,两组均作带十二指肠袢的同种异体胰腺移植 ,除B组供体标本灌注及术后加用维拉帕米外 ,两组围手术期处理均相同。结果 :2 0头猪中 18头及其移植胰存活两周以上 ,A、B组中各有 1例术后第 1天血栓形成致移植胰功能丧失。术后 1～ 3d两组C 肽有所下降 ,第 5天开始回升 ,维持 2w以上。两组同一时段比较B组C 肽高于A组 ,P <0 .0 5。术后第三天起 ,两组胰液淀粉酶开始升高 ,维持 2w以上 ,两组同一时段比较B组高于A组 ,P <0 .0 5。结论 :胰腺移植中供体器官灌注和术后使用维拉帕米可明显改善移植胰的功能。     

Professionalization of surgical abdominal organ recovery leading to an increase in pancreatic allografts accepted for transplantation in the Netherlands: a serial analysis

Professional abdominal organ recovery with certification has been mandatory in the Netherlands since 2010. This study analyses the effects of certification (January 2010–September 2015) on pancreas transplantation and compares it to an era before certification (February 2002–May 2008) for surgical injuries and the number of pancreases transplanted. A total of 264 cases were analysed. Eighty‐four recovered pancreases (31.8%) with surgically injuries were encountered. Forty‐six of those were surgically salvaged for transplantation, resulting in a total of 226 (85.6%) being transplanted. It was found that certified surgeons recovered grafts from older donors (36.8 vs. 33.3; P = 0.021), more often from donation after circulatory death (DCD) donors (18% vs. 0%; P < 0.001) and had less surgical injuries (21.6% vs. 41.0%; P < 0.001). Certification (OR: 0.285; P < 0.001) and surgeons from a pancreas transplant centre (OR: 0.420; P = 0.002) were independent risk factors for surgical organ injury. Predictors for proceeding to the actual pancreas transplantation were a recovering surgeon from a pancreas transplantation centre (OR: 3.230; P = 0.003), certification (OR: 3.750; P = 0.004), donation after brain death (DBD) (OR: 8.313; P = 0.002) and donor body mass index (BMI) (OR: 0.851; P = 0.023). It is concluded that certification in abdominal organ recovery will limit the number of surgical injuries in pancreas grafts which will translate in more pancreases available for transplantation.     

Pancreatico-renal composite transplant: a new technique designed to decrease pancreatic graft thrombosis

Abstract:  Pancreas graft thrombosis continues to be a major cause of graft loss. The removal of the donor spleen is accompanied by a significant reduction in pancreas graft blood flow. It is likely that reduced blood flow contributes to thrombosis in concert with other factors. We present a case of simultaneous pancreas and dual kidney transplantation wherein one donor kidney was anastomosed to the splenic vessels of the pancreas graft. The portal venous drainage of the pancreas graft was into the vena cava and duodenal segment was drained into the recipient's jejunum. Intraoperative blood flow determinations using an ultrasonic flow probe around the graft portal vein showed that the placement of the renal graft in the position of the donor spleen improved flow by approximately one-third (e.g. at 15 min after transplantation, 800 cc/min vs. 550 cc/min with the composite vascular pedicle clamped). The perfusion phase of a radionuclide scan on postoperative day 3 showed both transplanted kidneys had brisk and comparable visualization. The patient had an uneventful recovery and was discharged on the seventh postoperative day with normal blood glucose values and a serum creatinine of 1.2 mg/mL. A pancreatico-renal composite graft may decrease the incidence of thrombosis by improving pancreatic graft blood flow.     

Vascular catastrophes following pancreas transplantation: an evolution in strategy at a single center

Fridell JA, Johnson MS, Goggins WC, Beduschi T, Mujtaba MA, Goble ML, Powelson JA. Vascular catastrophes following pancreas transplantation: an evolution in strategy at a single center.
Clin Transplant 2012: 26: 164–172.
© 2011 John Wiley & Sons A/S. Abstract: Introduction: Complications of pancreas transplantation involving the arterial anastomosis are potentially life threatening. In this report, we review our experience with such vascular catastrophes. Methods: Pancreas transplants performed between January 2003 and December 2009 were reviewed. All cases of pseudoaneurysm (PA) or arterioenteric fistula (AEF) were included. Results: Of 346 pancreas transplants, 10 vascular catastrophes in nine recipients were identified. There were five PAs, one involving the pancreas allograft, one involving the donor iliac artery Y‐graft stump following allograft pancreatectomy, two involving the kidney allograft, and one involving the bifurcation of the Y‐graft. The latter was treated with coil embolization, but subsequently developed into an AEF. There were five AEFs including the recipient mentioned above. Four had a failed allograft and three had discontinued immunosuppression. The final case had a clamp injury to the proximal common iliac artery that fistulized to the donor duodenum. The management, course and outcome of all nine recipients are described in detail. Conclusion: Vascular catastrophes such as PA and AEF are potentially life‐threatening complications of pancreas transplantation. Immediate treatment at the time of bleeding is essential and covered stenting of the involved artery may provide immediate vascular control in these situations.     

A comparative study of pancreas transplantation between type 1 and 2 diabetes mellitus

BackgroundPancreas transplantation remains the best long-term treatment option to achieve physiological euglycemia and insulin independence in patients with labile diabetes mellitus (DM). It is widely accepted as an optimal procedure for type 1 DM (T1DM), but its application in type 2 DM (T2DM) is not unanimously acknowledged.MethodsIn total, 146 diabetes patients undergoing pancreas transplantation were included in this study. Clinical data and outcomes were compared between the T1DM and T2DM groups.ResultsMajority (93%) of the pancreas transplantations in T2DM were for uremic recipients. Complications occurred in 106 (73%) patients, including 70 (48%) with early complications before discharge and 79 (54%) with late complications during follow-up period. Overall, rejection of pancreas graft occurred in 37 (25%) patients. Total rejection rate in T2DM recipients was significantly lower than that in T1DM. The short- and long-term outcomes for endocrine function in terms of fasting blood sugar and hemoglobin A1c levels and graft survival rates are comparable between the T2DM and T1DM groups.ConclusionsT2DM is not inferior to T1DM after pancreas transplantation in terms of surgical risks, immunological and endocrine outcomes, and graft survival rates. Therefore, pancreas transplantation could be an effective option to treat selected uremic T2DM patients without significant insulin resistance.     

The use of low dose octreotide prophylaxis in pancreatic transplants with enteric drainage. Results of a prospective randomized single center trial

AIM: The aim of this study was to investigate the effect of octreotide in the perioperative course of pancreas transplants drained into the bowel in terms of fistula formation, pancreatitis, hemorrhage and thrombosis, and to compare the results to patients not receiving octreotide in a prospectively, randomized single center trial. PATIENTS AND METHODS: Forty pancreas transplant recipients were prospectively randomized to either receive or not to receive octreotide 0.1 mg subcutaneously at the time of operation and 3x/d there after until post-operative day 7. The incidence of pancreatic leakage from the anastomosis and the content of peritoneal fluid drainage regarding amylase and lipase concentrations collected by abdominal drains were registered on day 0-10. Both groups were comparable for age, sex, onset of diabetes, surgical procedure and immunosuppressive regimen. RESULTS: There were 35 simultaneous pancreas-kidney transplants and five solitary pancreas transplants, two in the octreotide and three in the control group two pancreas after kidney, one pancreas after liver pancreas, one pancreas after simultaneous pancreas kidney transplantation, one pancreas transplant alone. All had enteric drainage. Twenty patients received octreotide and 20 did not. In one patient, receiving octreotide the pancreas had to be removed for septic complications because of an enteric fistula arising from the anastomosis (1/20 = 5%). The incidence in patients on octreotide vs. non-octreotide was 1 vs. 0 for pancreatitis, 2 vs. 3 for hemorrhage, 2 vs. 1 for thrombosis and 2 vs. 0 for pancreatic fistulae resulting in an actual overall 12 months patient survival of 100% in both groups and a pancreas survival of 85% vs. 95%. For primary simulaneous pancreas kidney the pancreas graft survival was 93%. The amylase and lipase concentrations of fluid collections drained into the peritoneum on day 0 to 10 post-operatively indicating pancreatic fistulization was comparable in both groups. CONCLUSION: The use of octreotide following pancreas transplantation did not prevent pancreatic fistula formation from the anastomosis neither from the pancreatic capsule in pancreas transplantation with enteric drainage. Further studies are required to finally evaluate the benefit of this prophylactic treatment.