Pancreas Autotransplantation Research Articles

Islet Autotransplantations for Total Pancreatectomy

Total pancreatectomy (TP) is performed for not only malignant pancreatic diseases but also benign disease like chronic pancreatitis or pancreatic injury. However, it always abolishes the pancreatic exo- and endocrine functions and the nutritional condition of the patients is significantly impaired. Thus, especially in the case of benign diseases, the additional treatment for recovering endocrine function is recommended because the permanent endocrine dysfunction must influence their quality of life. Islet and pancreas transplantations are the surgical treatments which can recover the endocrine function of the severe diabetic patients by the transplantations of pancreatic islet and organ. In the case of autotransplantation, islet autotransplantation (IATx) is performed for the patient in benign pancreatic disease who cannot be avoided the abolishment of the endocrine function due to TP to rescue the function and prevent the onset of secondary diabetes mellitus. In this review article, we show the current status of the TP with IATx including our case. Furthermore, we also show the pancreas autotransplantation (PATx) which was performed in historical.

Six-Year Graft Survival After Partial Pancreas Heterotopic Auto-Transplantation: A Case Report

BackgroundLong-term graft survival of partial pancreas auto-transplantation after total pancreatectomy has not been clarified. The clinical implications of repeat completion pancreatectomy for locally recurrent pancreatic carcinoma in the remnant pancreas after initial pancreatectomy also have not been clarified. MethodsWe have previously reported a 61-year-old woman presenting with re-sectable carcinoma of the remnant pancreas at 3 years after undergoing a pylorus-preserving pancreaticoduodenectomy for invasive ductal carcinoma of the pancreas head. We also performed distal pancreas auto-transplantation with the use of a part of the resected pancreas to preserve endocrine function. ResultsThe patient was discharged at 20 days after surgery without any complications. She had been followed regularly in our outpatient clinic. She had been treated with S-1 as adjuvant chemotherapy; 72 months after the completion total pancreatectomy with distal partial pancreas auto-transplantation, the patient was alive without any evidence of the pancreatic carcinoma recurrence. The pancreas graft was still functioning with a blood glucose level of 112 mg/dL, HbA1C of 6.7%, and serum C-peptide of 1.2 ng/mL; and urinary C-peptide was 11.6 μg/d. ConclusionsOur patient demonstrated that repeated pancreatectomies can provide a chance for survival after a locally recurrent pancreatic carcinoma if the disease is limited to the remnant pancreas. An additional partial pancreas auto-transplantation was successfully performed to preserve endocrine function. However, the indications for pancreas auto-transplantation should be decided carefully in the context of pancreatic carcinoma recurrence.

Heterotopic pancreas autotransplantation with spleen for uncontrollable hemorrhagic pseudocyst and disabling pain in chronic pancreatitis.

In this study, we report on a heterotopic segmental pancreatic autotransplantation (HPAT) with spleen for alcoholic chronic pancreatitis with uncontrollable hemorrhagic pseudocyst and complete portal venous obstruction. The patient was a 72-year-old man who had an alcoholic chronic pancreatitis with severe abdominal pain and hemorrhagic pseudocyst. The first bleeding from a pseudoaneurism of the gastro-duodenal artery (GDA) to the cyst of pancreas head was stopped by interventional radiology (IVR) at our hospital on May 2010. The second bleeding happened with severe abdominal pain on February 15th, 2011; he was admitted on February 17. The IVR was not successful. There were two problems for the operation. The first was the severe inflammation and the second was the control of hemorrhage from GDA. We were afraid of the postoperative hemorrhage due to the leakage of pancreatic juice in the pancreato-duodenectomy (PD). Therefore, we chose the HPAT as a solution for postoperative hemorrhage and severe abdominal pain. After complete duodeno-pancreatectomy with spleen, we performed HPAT with spleen on March 8, 2011. The pancreatic duct reconstruction was performed by Roux-en-Y anastomosis to the jejunum. The postoperative course was uneventful. The abdominal pain had resolved completely and the patient remained normoglycemic after HPAT. We conclude that HPAT is a useful option for hemorrhagic pseudocyst of the pancreas head with severe abdominal pain of chronic pancreatitis.

Intraoperative islet isolation for pancreas autotransplantation: A novel technique

Intraoperative islet isolation for pancreas autotransplantation: A novel technique

Total Pancreatectomy Combined with Partial Pancreas Autotransplantation for Recurrent Pancreatic Cancer: A Case Report

We describe a patient presenting with a resectable carcinoma of the remnant pancreas at 3 years after undergoing a pylorus-preserving pancreaticoduodenectomy for invasive ductal carcinoma of the pancreatic head. We also performed a distal pancreas autotransplantation using a part of the resected pancreas to preserve endocrine function. Final histologic findings showed the second tumor to be an invasive ductal carcinoma consisting of a well-differentiated tubular adenocarcinoma with similar histopathologic findings as the first tumor. There were no microscopic lymph node metastases and no evidence of microvascular invasion (pStage IA [pT1, pN0, M0] and R0 according to the International Union Against Cancer TNM classification). The patient was discharged at 20 days after surgery without any trouble and followed by adjuvant chemotherapy with S-1. The carbohydrate antigen 19-9 value was again normalized after the second surgery. Twenty months after the second operation, the patient is alive without cancer recurrence. The pancreas graft is functioning with a blood glucose of 108 mg/dL, HbA1C of 6.2%, and serum C-peptide of 1.4 ng/mL.

Possible role of heat shock protein 60 in reducing ischemic-reperfusion injury in canine pancreas grafts after preservation by the two-layer method.

Recently, results of the clinical application of the two-layer method have shown the morphologic quality of the human pancreas grafts after reperfusion to be excellent, although ischemia-reperfusion injury is related to early graft loss in pancreas transplantation. However, some reports have indicated that heat shock proteins (HSPs) have important functions in response to the stress-related events. To examine whether the two-layer method reduced ischemia-reperfusion injury in a canine pancreas autotransplantation model by investigating the expression of HSPs. There were three experimental groups in which dogs received segmental autografts after preservation by the two-layer method using University of Wisconsin solution (UW) (group 1), simple storage in UW (group 2) for 24 hours, or no preservation (group 3). In group 1, pancreatic tissue perfusions were high, and pancreatic exocrine functions were well preserved after 1, 2, and 4 hours of reperfusion with low incidence of graft pancreatitis or vessel thrombosis compared with that in group 2. Moreover, ATP rapidly recovered, and HSP 60 was strongly enhanced after reperfusion in group 1. On the other hand, ATP recovery and the enhancement of HSP 60 were weak after reperfusion in group 2. The two-layer method reduced ischemia-reperfusion injury compared with UW simple storage in canine pancreas autotransplantation with a strong expression of HSP 60.

Long-term duct-occluded segmental pancreatic autografts: absence of microvascular diabetic complications.

Current insulin therapies for control of glucose metabolism in patients with type I diabetes mellitus prevent major metabolic consequences of insulin deficiency, but none prevents or arrests long-term complications. In experimental models of canine diabetes, retinopathy, neuropathy, and nephropathy have been shown to develop within 5 years. The aim of this study was to determine in a canine model whether glucose control provided by segmental duct-occluded pancreas autografts could prevent the long-term complications of diabetes. Thirty-five outbred mongrel dogs underwent segmental pancreas autotransplantation with residual pancreatectomy. Follow-up over 5 years included endocrine, retinal fundus photography, fluorescein angiography, and nerve conduction studies. At endpoint, analysis of organ specific changes was undertaken. Long-term survival was achieved in 14 dogs for 4 to 5 years and in 3 dogs for 3 to 5 years. Glycosylated hemoglobin levels remained within normal limits, although response to glucose challenge was suboptimal. Fundus photography and fluorescein angiography demonstrated the absence of retinal vascular aneurisms, capillary leakage, and obliteration. Retinal digest showed no vascular changes and normal endothelial/pericyte ratios. Nerve conduction was normal, and histology of nerves revealed normal density of myelinated fibers and absence of intrafascicular vessels and glycogen deposits, with no change in spectrum of fiber diameters and ovoids. Renal histology revealed no evidence of nephropathy with normal glomerular basement membranes. We have demonstrated that duct-occluded segmental pancreatic autografts are capable of providing satisfactory metabolic control for up to 5 years, thereby preventing development of the long-term microvascular complications of diabetes.

Pancreas autotransplantation in pig with systemic or portal venous drainage. Effect on the endocrine pancreatic function after transplantation.

The effect of the type of venous drainage of the graft on its endocrine function was studied in two groups of pigs after segmental pancrease autotransplantation. Group 1 comprised 10 pigs with portal venous drainage (PVD) and group 2 comprised 10 pigs with systemic venous drainage (SVD). The graft consisted of body and tail of the pancreas. The pigs were totally pancreatectomized. The pancreatic duct was occluded by neoprene injected into the duct. One week before and 1 and 3 months after transplantation, intravenous glucose tolerance (IVGTT) and meal stimulation tests (MST) were performed. Plasma glucose (PG), insulin (INS), C-peptide, glucagon (GLU),and pancreatic polypeptide (PP) were measured during the tests. All pigs had normal fasting PG, 1 and 3 months after PanTx, although MST disclosed significantly higher PG (P<0.05) during the test after transplantation. In the PVD group, a decrease in INS level during both test was recorded after PanTx (P<0.05), while in the SVD group a nonsignificant rise in INS level was recorded compared with before transplant. A significant difference (P<0.05) in INS levels were present both 1 and 3 mon. after PanTx between the two groups. Pigs with PVD showed a higher (P<0.05) C-peptide level than pigs with SVD during IVGTT. The initial significant rise in PP during MST and the initial fall in PP during IVGTT recorded in all pigs before transplantation were totally lost after transplantation in both groups. During the tests, PP remained steady and significantly lower than the pretransplantation levels in both groups. A significantly higher GLU level during both IVGTT and MST was observed in SVD compared with PVD 1 month after PanTx (P<0.05), being more pronounced during MST. This accentuated GLU concentration decreased by 3 months after transplantation, although it was still significantly greater than pretransplantation levels. We concluded that the unnatural mode of delivery of pancreas endocrine secretion to systemic rather than to portal circulation leads to derangements in pancreatic endocrine function in order to maintain glucose homeostasis. This may cause earlier exhaustion of islet cells. Segmental rather than whole organ and duct occlusion rather than exocrine drainage may further contribute to this, shortening the effective life of the graft.

The effect of pancreatic polypeptide on glucose disposal after surgical alterations of the pancreas.

Surgical alterations of the pancreas result in anatomic changes that can affect postoperative glucose metabolism. Pancreas transplantation results in reduction of beta-cell mass, systemic release of insulin, and denervation. The authors hypothesized that such alterations affect peripheral glucose disposal to induce an "insensitivity" to endogenously (systemically) released insulin. Additionally, they hypothesized that surgically induced deficiency of the postprandial hormone, pancreatic polypeptide, might contribute to altered glucose disposal. The authors studied two surgical models in dogs known to be devoid of pancreatic polypeptide--70% proximal pancreatectomy (PPx) and PPx plus distal pancreas autotransplantation (PAT/B). Oral glucose challenge and euglycemic hyperinsulinemic clamp studies were performed before and after a 16-day "pulsed" infusion of pancreatic polypeptide. Both surgical procedures resulted in elevations in the integrated glucose response after oral glucose, which was not affected by pancreatic polypeptide infusion. Euglycemic clamp studies showed decreased hepatic glucose output (Ra) and overall glucose disposal (Rd) in the fasted state for both surgical groups. The transplant animals demonstrated significant decreases in Rd during the hyperinsulinemic challenge (3.2 +/- 0.01 versus 5.7 +/- 0.01 mg/kg/minute at 60 to 120 minutes for PAT/B versus control). After 16 days of pancreatic polypeptide infusion, however, basal Ra, as well as basal and 60- to 120-minute Rd values, were returned to control values in the transplant group. The authors conclude that pancreas transplantation results in altered glucose disposal, possibly due to an altered effectiveness of systemically released insulin. They conclude that pancreatic polypeptide is an important modulator of peripheral insulin action. Therefore, the role of pancreatic polypeptide must be taken into account when evaluating postoperative glucose metabolism in canine models of pancreas transplantation.

Effect of exogenous somatostatin on endocrine and exocrine functions of the segmental autotransplanted pancreas in man

Effect of exogenous somatostatin on endocrine and exocrine functions of the segmental autotransplanted pancreas in man

Successful 96-Hr cold-storage preservation of canine pancreas with UW solution containing the thromboxane A2 synthesis inhibitor OKY046

Prostanoids, such as prostacyclin (PGI) and thromboxane A2 (TxA), have been recently suggested to play an important role in preservation-induced injury of pancreas grafts. We have previously shown that the TxA synthesis inhibitor OKY046 prevents a decrease of both the PGI/TxA ratio and blood flow in pancreas grafts after 24-hr preservation with Euro-Collins solution. In our present study, we analyzed whether OKY046 added to University of Wisconsin (UW) solution could extend successful cold-storage preservation of segmental canine pancreas grafts, compared with UW alone. We divided 30 dogs into four preservation groups: Group 1, UW solution for 72 hr ( n = 7); Group 2, UW solution for 96 hr ( n = 8); Group 3, UW solution plus OKY046 (10 −4 M) for 72 hr ( n = 7); and Group 4, UW solution plus OKY046 (10 −4 M) for 96 hr ( n = 8). After the cold storage period, segmental pancreas autotransplantation with immediate completion pancreatectomy was done. Preservation was deemed successful if serum glucose < 150 mg/dl was maintained for at least 5 days. Intravenous glucose tolerance tests and biopsies were done in those dogs with functioning grafts 14 days post-transplant. Successful preservation rates were as follows: Group 1, 57.1%; Group 2, 12.5%; Group 3, 100%; and Group 4, 75%. The mean K values (± standard error) were: Group 1, 1.54 ± 0.13; Group 2, 0.59; Group 3, 1.54 ± 0.14; and Group 4, 1.59 ± 0.24 (not statistically different). In contrast, the initial insulinogenic indices of both Group 3 (0.066 ± 0.008) and Group 4 (0.113 ± 0.022) were significantly higher than in Group 1 (0.054 ± 0.006) ( P < 0.05). In addition, pancreas biopsies showed almost normal architecture of both endocrine and exocrine cells in Group 4, but considerable fibrosis in Group 2. We conclude that adding OKY046 in UW solution results in good viability after prolonged cold storage and extends successful pancreas preservation to 96 hr in the canine autotransplant model.

Successful 96-hour preservation of the canine pancreas.

We tested the preservation of the pancreas for 96 h by a modified two-layer (UW solution/perfluorochemical) cold storage method (group 1) in the canine model of pancreas autotransplantation and compared this with an original two-layer (Euro-Collins' solution/perfluorochemical) cold storage method (group 2) and simple cold storage method with UW solution (group 3). A graft was considered functioning if the dog had a normal blood glucose for at least 5 days after transplantation. The functional success rates after preservation for 72 h were 100%, 100% and 80% for groups 1, 2 and 3 respectively. On the other hand, the functional success rates for groups 1, 2 and 3 after preservation for 96 h were 75%, 0% and 0% respectively. The mean K value of 96-hour preserved grafts for group 1 at 2 weeks after transplantation was 1.52 +/- 0.30 compared with 1.98 +/- 0.48 before preservation. Biopsies of grafts from group 1 showed almost normal pancreatic architecture even after preservation for 96 h. In addition, biopsies of grafts preserved for 96 h in group 1 at 4 weeks after transplantation showed almost normal endocrine tissue with mild fibrosis of the exocrine tissue. This study demonstrated the possibility of preserving the pancreas for 96 h prior to transplantation.

CORRELATION BETWEEN HIGH ADENOSINE TRIPHOSPHATE TISSUE CONCENTRATION AND GOOD POSTTRANSPLANT OUTCOME FOR THE CANINE PANCREAS GRAFT AFTER PRESERVATION BY THE TWO-LAYER COLD STORAGE METHOD

Assessment of viability of a pancreas graft during preservation is very important to avoid transplantation of a nonfunctioning allograft. In the present report the correlation between adenosine triphosphate tissue concentration at the end of cold preservation by the two-layer method and viability a of canine pancreas graft following transplantation was studied. After preservation by an original two-layer (Euro-Collins' solution/perfluorochemical) method (group 1) and a modified two-layer (University of Wisconsin solution/PFC) method (group 2) for 24, 48, 72, 96, and 120 hr (subgroups A, B, C, D, and E), the tissue concentration of ATP was determined using high-performance liquid chromatography, and the viability of the pancreas graft was tested in the canine model of segmental pancreas autotransplantation. Maintenance of normoglycemia for at least five days after transplantation was considered to indicate a viable pancreas graft. In group 1, functional success rates were A: 5/5, (100%), B: 4/4 (100%), C: 4/4, (100%), and D: 0/4 (0%), respectively. The ATP tissue concentrations were 7.47 +/- 0.47 (n = 5), 7.91 +/- 1.21 (n = 4), 8.29 +/- 0.21 (n = 4), and 4.94 +/- 1.11 (n = 4) mumol/g dry weight in groups 1A, 1B, 1C, and 1D, respectively. There was a statistically significant difference between viable groups (groups 1A, 1B, and 1C, 7.86 +/- 0.77 mumol/g dry weight [n = 13]) and the nonviable group (group D, 4.94 +/- 1.11 mumol/g dry weight (n = 4) (P less than 0.01). On the other hand, the functional success rates were 3/3 (100%), 3/3 (100%), 3/3 (100%), 5/7 (71%), and 0/3 (0%) in groups 2A, 2B, 2C, 2D, and 2E, respectively. Two of seven dogs died of causes related to the grafts (pancreatitis and thrombosis). The ATP tissue concentrations were 8.53 +/- 1.45 (n = 3), 9.64 +/- 1.77 (n = 3), 13.81 +/- 2.09 (n = 3), and 12.49 +/- 2.52 (n = 5) mumol/g dry weight in groups 2A, 2B, and 2C and in viable grafts in group 2D, respectively, but the ATP tissue concentration of nonviable grafts in group 2D and group E were 3.51 +/- 0.81 (n = 2) and 3.98 +/- 1.34 (n = 3) mumol/g dry weight, respectively. There was a statistically significant difference between viable groups (groups 2A, 2B, 2C and viable grafts in group 2D, 11.03 +/- 2.72 mumol/g dry weight [n = 14]) and nonviable groups (group E and nonviable grafts in group 2D, 3.79 +/- 1.06 mumol/g dry weight [n = 5]) (P less than 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)

Glucose Metabolism After Pancreas Autotransplantation The Effect of Open Duct Versus Urinary Bladder Drainage Technique

Glucose metabolism and insulin secretion after pancreas transplantation may be affected by the technique used for ductal drainage. We evaluated peripheral glucose and insulin levels after oral (oral glucose tolerance test [OGTT]) and sustained stable hyperglycemic challenge (clamp) in dogs who had undergone pancreas autotransplantation with intraperitoneal drainage (PAT) or with urinary bladder to pancreatic duct anastomosis (PAT/B). Both groups had basal glucose values comparable to normal controls; PAT/B animals had fasting hyperinsulinemia. Pancreas autotransplantation animals had an increased integrated glucose response to OGTT and blunted insulin response to hyperglycemic clamp. Urinary bladder to pancreatic duct anastomosis animals had a significantly decreased integrated glucose response to OGTT compared to PAT and an exaggerated insulin response to hyperglycemic challenge, which approximated normal control values by the last 30-minute period of the clamp. Interestingly M values, which approximate glucose metabolized during the hyperglycemic challenge, were depressed in both surgical groups. It is concluded that the technique of bladder drainage allows a 'normalization' of peripheral levels of insulin that is associated with amelioration of an altered glucose response after oral challenge. However the clamp studies show that, despite the improvement in insulin response, an insensitivity may exist to a wide range of endogenous levels after pancreas transplantation.

Glipizide Treatment of Pancreas Autotransplantation: Effects on Alterations in Glucose-Insulin Relationships

Pancreas transplantation has been proven effective in supplying an endogenous insulin supply in diabetics. However, alterations in glucose metabolism after transplantation suggest a possible "insensitivity" to its action in the periphery. We hypothesized that sulfonylurea treatment of canines who had received segmental pancreas autotransplants would correct these alterations by altering peripheral insulin sensitivity. Glipizide therapy (5 mg p.o. b.i.d.) did appear, in fact, to enhance basal insulin sensitivity by lowering fasting glucose (100 +/- 3 to 81 +/- 11 mg/dl pre-treatment to post-treatment) while not affecting basal insulin levels. However, glipizide therapy was associated with decreased insulin response to challenge by either oral glucose (2 gm/kg) or sustained intravenous hyperglycemia (150 mg/dl above basal). We conclude that our model of pancreas autotransplantation documents alterations in glucose metabolism which are devoid of the effect of immunosuppression. Glipizide treatment appears to affect fasting sensitivity to insulin, but results in a decrement of insulin response to oral or intravenous glucose challenge.

Seventy-two-hour preservation of the canine pancreas by the two-layer (Euro-Collins' solution/perfluorochemical) cold storage method.

A 72-hr preservation of canine pancreas by a 2-layer (Euro-Collins'/Perfluorochemical) cold storage method was tested in the canine model of segmental pancreas autotransplantation. The functional recovery of the grafts by this method (group 1) was determined by daily fasting blood glucose concentration and intravenous glucose tolerance test at 2 weeks after autotransplantation and compared with simple cold storage with Euro-Collins' solution (group 2) and control (no preservation) (group 3). Maintenance of normoglycemia for at least 5 days after transplantation was considered a successful preservation. The functional success rates after 72-hr preservation were 100%, 0%, and 100% for groups 1, 2, and 3, respectively. The mean K values of group 1 after 72-hr preservation was 1.78 +/- 0.42 compared with 2.05 +/- 0.32 for group 3 at 2 weeks after transplantation. Biopsies of grafts of group 2 after 72-hr preservation showed remarkable autolytic changes in exocrine and endocrine tissues. In contrast, biopsies of grafts of group 1 after 72-hr preservation showed almost normal architecture in both tissues. In addition, biopsies of 72-hr preserved grafts of group 1 at 4 weeks after after autotransplantation showed almost normal pancreas architecture with minimal fibrotic changes in the exocrine tissue. This study demonstrated the possibility of 72-hr preservation of the pancreas for transplantation.

Exocrine Function of the Heterotopic Transplanted Pancreas Segment

We investigated the effect of denervation after heterotopic segmental pancreas autotransplantation on the exocrine function of the graft. The weight of the pancreas segment was determined, and secretory volume, bicarbonate output, and amylase activity were measured before and after i.v. infusion of secretin and cholecystokinin (CCK)-8. The studies were performed in untreated normal dogs, at 2 months postoperatively in partially pancreatectomized dogs with an innervated segment left in situ, and in totally pancreatectomized recipients of denervated heterotopic autotransplanted segments (approximately 30% of whole pancreas). The weight of the pancreas segment was similar in innervated and denervated dogs. Basal pancreatic secretory volume, bicarbonate output, and amylase activity were largely independent of cholinergic control. The secretory volume and bicarbonate output response to i.v. gut hormones (mainly secretin) were slightly modulated by cholinergic activity, whereas amylase response to gut hormones (mainly CCK-8) was quite independent of cholinergic control. We conclude that, after pancreas transplants, the effect of denervation on graft exocrine function is negligible--a finding that is reassuring if preserving of the exocrine tissue is important for optimal endocrine function of the graft.

Pancreatic endocrine responses to nutrients and bombesin after segmental pancreas autotransplantation in dogs.

The capacity of autotransplanted (ATP) distal pancreas segments with systemic venous and peritoneal exocrine drainage to support physiologic control of plasma glucose levels was tested, and compared with the functions of "simulated autotransplants" (SATP) prepared with similar dissection and peritoneal exocrine drainage, but with hepatic portal venous drainage, in dogs. In ATP in the postabsorptive state, plasma levels of glucose, immunoreactive insulin (IRI) and immunoreactive glucagon (IRG1) were normal. Autotransplants resulted in impaired glucose tolerance after meals with impaired early insulin responses, and the normal brisk rise of IRG1 in the plasma was delayed and reduced through the first 30 min of feeding. In ATP, also, the response to bombesin was abnormal; the normal stimulation of release of both IRI and IRG1 was delayed in both cases. In studies of responses to oral and intravenous glucose in ATP and SATP dogs, similar mild degrees of glucose intolerance were found with both routes of administration; however, whereas in ATP dogs increases of IRI were highly exaggerated with both routes of administration of glucose, in SATP dogs plasma IRI rose from subnormal levels in the postabsorptive state through subnormal increments with both routes of administration. Further studies are necessary to determine the relative importance of denervation and reduction of the mass of the pancreas in these effects, and to assess the significance of the differences in blood insulin levels in the two preparations.

72-hour preservation of the canine pancreas.

A new flushout solution for preservation of the pancreas was tested in the dog model of segmental pancreas autotransplantation. The solution osmolality was 320 mOsm/L, K+ = 120 mM, Na+ = 30 mM, and it contained the anion, lactobionate, and raffinose as impermeants to the cell. Preservation times studied were 48 and 72 hr. The pancreas was flushed out with about 250 ml of the new solution and stored at 0 degrees C. Dogs were monitored postoperatively for blood glucose and intravenous glucose tolerance (IVGTT). Results were compared with control (no preservation) segmental pancreas autotransplants. Dogs receiving pancreases stored for 48 or 72 hr were normoglycemic on day one and remained normoglycemic for at least 28 days, or until time of sacrifice. Two of four dogs with pancreases stored for 48 hr were sacrificed on day 14 with normal IVGTT for histology. The remaining two dogs had normal pancreatic function for 28 days. Two of eight dogs receiving pancreas grafts after 72-hr cold storage died of causes unrelated to the pancreas graft, which was still functioning at the time of death. Six dogs remained normoglycemic and had a normal IVGTT at least for 28 days. This study demonstrates the feasibility of preserving the pancreas for three days for transplantation.

Evaluation of insulin secretion after pancreas autotransplantation by oral or intravenous glucose challenge.

Segmental pancreatic autotransplantation is accompanied by surgical alterations to the pancreas that may have consequences for carbohydrate metabolism. Four mongrel dogs were evaluated before operation and sequentially until 40 weeks after total pancreatectomy and autotransplantation of the splenic lobe of the pancreas with bolus intravenous and oral administration. Intravenous glucose tolerance test (IVGTT) (0.5 g/kg) revealed maintenance of fasting euglycemia for as long as 40 weeks after operation. Peak glucose and integrated glucose values did not show significant changes as a result of autotransplantation. Following transplantation, a delayed peak insulin response was seen; however, basal, peak, and integrated insulin values were largely unaltered. Only K values, a measure of glucose disposal, showed severe alterations (2.44 +/- 0.21 before operation to 1.24 +/- 0.30 at 40 weeks after operation). Oral glucose tolerance tests (OGTT) (2.0 g/kg) demonstrated an increased peak hyperglycemic response after autotransplantation with increased integrated glucose responses. Insulin levels remained at those levels seen before operation, and glucose-dependent insulinotropic polypeptide (GIP) responses were unchanged during the OGTT as late as 20 weeks after operation. In conclusion, pancreas autotransplantation after total pancreatectomy results in significant metabolic alterations that the IVGTT fails to detect with absolute glucose or insulin levels. However, K values are significantly lowered, which indicates alterations in cellular glucose transport. The OGTT demonstrates hyperglycemia without increased insulin or GIP levels, which suggests an altered beta cell response to the enteric stimulus of insulin release. These changes are nonetheless well tolerated by animals that have remained clinically healthy and euglycemic in the basal state.