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PubMed2004

[Pancreas transplant pathology: clinicopathologic and experimental findings].

134 pancreas transplantations (113 simultaneous pancreas-kidney, 5 pancreas after kidney, 16 pancreas transplants alone) done in Rostock from VI/95 to III/04 were evaluated in respect to pancreas transplant lesions. Additionally, 36 pancreas specimen of Brown Norway rats experimentally transplanted into diabetic Lewis rats were examined. From 55 out of the 134 pancreas transplant patients, 122 partly repeated pancreas graft specimen examinations were carried out morphologically. The principal lesions in the human pancreas transplants were acute (enzymatic) necrotizing transplant pancreatitis (41 samples), acute (13) and chronic (14) transplant rejection specimen as well as primary or secondary graft thrombosis (12 probes). 23 probes were zero-hour biopsies and 2 showed normal tissue. From 69 out of the 118 pancreas transplant patients with an additional kidney graft, a total of 159 renal transplant probes were examined. They showed the following lesions: acute tubular damage or acute renal failure (23), acute (56) or chronic (22) kidney graft rejection, acute tubular cyclosporine or FK 506 toxicity (53), and histologically normal graft tissue (8 cases). As in other grafted organs, the changes occurring in the transplanted pancreas consist of varying lesions related and/or not related to pancreas transplant rejection. A concise classification and a reproduceable grading schedule are suggested for diagnostic, differential diagnostic, therapeutic, and prognostic purposes. Pancreatic rejection lesions can be classified according to a proposed Rostock '04 working classification of pancreas allograft rejection into three grades (I: mild, II: moderate, III: severe) both for acute and chronic pancreas rejection. There was no direct correlation of the findings in 21 patients with simultaneously studied pancreas and renal transplant biopsies. In contrast to renal grafts, pancreatic rejection signs were often superimposed by acute transplantation pancreatitis with or without secondary graft thrombosis, nonenzymatic necroses or infection. Experimental acute pancreas transplant rejection in rats showed quite similar findings to human grafts and was also graded into three different acute rejection stages.

Animals↗
PubMed2006

Clinical implications of incomplete pancreas divisum.

CONTEXT: Incomplete pancreas divisum is a pancreatic anomaly that results in an inadequate communication between the ventral and dorsal pancreatic ducts. Although the relationship between complete pancreas divisum and pancreatitis has been contentious, clinical implications of incomplete pancreas divisum have not been noted. OBJECTIVE: This study was done to investigate the clinical significance of incomplete pancreas divisum. PATIENTS AND METHODS: We studied the anatomy of the pancreatic duct system in 3,220 cases using endoscopic retrograde pancreatography; 44 cases had complete pancreas divisum, and 41 had incomplete pancreas divisum. MAIN OUTCOME MEASURE: The prevalence of chronic and acute pancreatitis associated with complete or incomplete pancreas divisum was compared with that of cases with neither complete nor incomplete pancreas divisum (controls). RESULTS: All of the patients with complete or incomplete pancreas divisum who abused alcohol had chronic or acute pancreatitis. The prevalence of chronic pancreatitis in patients with complete or incomplete pancreas divisum was significantly higher than in controls (P<0.001 and P=0.001, respectively), but acute pancreatitis occurred more frequently only in patients with complete pancreas divisum (P=0.010). When we considered pancreatic-type pain as a pancreatitis-like disease, complete and incomplete pancreas divisum were suspected as the cause of pancreatitis-like disease in 39% (15/38: chronic dorsal pancreatitis, n=5; acute pancreatitis, n=7; pancreatic-type pain, n=3) and 30% (10/33: chronic dorsal pancreatitis, n=2; acute relapsing pancreatitis, n=1; pancreatic-type pain, n=7) of patients who did not abuse alcohol, respectively. CONCLUSIONS: Although the precise pathophysiology may differ, patients with complete pancreas divisum and patients with incomplete pancreas divisum may have similar presentations and a similar prevalence. The clinical implications of incomplete pancreas divisum may be similar to those of complete pancreas divisum.

Acute Disease↗
PubMed1990

Elimination of acute GVHD and prolongation of rat pancreas allograft survival with DST cyclosporine, and spleen transplantation.

Allogeneic spleen transplantation has been shown to have a tolerizing effect on pancreas allograft survival in rats. In this study we examined the effect of blood transfusions and cyclosporine administration on both rat pancreas allograft survival and acute graft-versus-host disease in BN recipients of Lewis pancreas-spleen allografts. We found that in this strain combination significant pancreas allograft prolongation occurred when the spleen was included en bloc with the pancreas graft. However, 50% of these recipients developed GVHD and died. A single donor-specific transfusion delivered to BN recipients of Lewis pancreas and pancreas-spleen allografts did not extend graft survival, but precluded the development of GVHD. A short, 6-day, and long, 26-day, course of CsA to recipients of pancreas and pancreas-spleen allografts extended graft and animal survival times, although not indefinitely. All pancreas-spleen recipients of both CsA protocols died following acute GVHD. Combined DST and CsA (short and long-course) administration in pancreas-only allograft recipients was deleterious to graft survival, compared with CsA administration alone. However, in pancreas-spleen recipients, combined DST and CsA had an additive effect. Moreover, in DST and long-course CsA-treated pancreas-spleen recipients, indefinite graft survival occurred with no signs of acute GVHD. The beneficial effect of the spleen allograft on pancreas graft survival was not dependent upon GVHD, since splenic-induced prolongation of pancreas graft survival was observed in the F1-donor to parent-recipient combination.

Acute Disease↗
PubMed1996

The effect of preservation temperature and period on resuscitation of the ischemically damaged canine pancreas during preservation by the two-layer (University of Wisconsin solution/perfluorochemical) method.

We have shown that 24 to 48 hour-preservation by the two-layer (University of Wisconsin solution (UW)/perfluorochemical (PFC)) method at 4 degrees C resuscitates a canine pancreas subjected to 90 min of warm ischemia. However, it is necessary to shorten preservation period for resuscitation of the ischemically damaged pancreas in a clinical simultaneous pancreas-kidney transplantation. The purpose of this study was to clarify the effect of preservation temperature and period on the resuscitation of the ischemically damaged pancreas during preservation by the two-layer method. First of all, we examined the possibility of resuscitation of the ischemically damaged pancreas during short-term preservation by the two-layer method. After 90 minutes of warm ischemia, canine pancreases were preserved by the two-layer method at 4, 20, or 37 degrees C. In control group, the pancreas graft was autotransplanted without preservation. Graft viability was judged by graft survival after autotransplantation. Pancreas grafts subjected to 90 min of warm ischemia were not viable (0/5). At 4 degrees C, 5 to 12 hr-preservation did not resuscitate the grafts (0/3 and 0/3 respectively). At 20 degrees C, 3 and 5 hr-preservation resuscitated the grafts (3/5 and 5/5 respectively), although 1 and 8 hr-preservation were not successful (0/3 and 0/3 respectively). At 37 degrees C, all the grafts were not resuscitated irrespective of preservation period. It was clear that the ischemically damaged pancreas was resuscitated during shot-term preservation by the two-layer method only at 20 degrees C. Secondly, we measured tissue adenine nucleotide levels by high performance liquid chromatography and pancreatic tissue perfusions using H2 clearance technique on reperfusion and examined the viability of vascular endothelium by nuclear trypan blue staining to make clear the necessary conditions for resuscitation of the ischemically damaged pancreas at 20 degrees C. ATP tissue levels in one hr-preserved grafts were 2.55 +/- 0.38 mumol/g dry weight and were significantly lower compared with the levels in 5 and 8 hr-preserved grafts, 9.40 +/- 2.09 (P < 0.01) and 7.37 +/- 1.06 mumol/g dry weight (P < 0.01) respectively. On the other hand, nuclear trypan blue uptakes of endothelial cells in 8 hr-preserved grafts were 37.6 +/- 11.6% and were significantly higher than 1 hr- and 5 hr-preserved grafts 5.6 +/- 4.5 (P < 0.01) and 5.0 +/- 3.0% (P < 0.01) respectively. As a consequence, pancreatic tissue perfusions in 8 hr-preserved grafts, 31.0 +/- 3.5 ml/min/g, were significantly lower than 1 hr- and 5 hr-preserved graft 72.0 +/- 11.6 (P < 0.01), 63.9 +/- 13.3 ml/min/g (P < 0.01) respectively. However, thromboxane A2 synthesis inhibitor (OKY046 0.1 mM/L) decreased the percentage of trypan blue uptake (8.2 +/- 3.6%) without interfering ATP synthesis (8.44 +/- 0.92 mumol/g dry weight) in 8 hr-preserved pancreas and tissue perfusions after reperfusion were dramatically improved (99.6 +/- 11.8 ml/min/g). As a result the ischemically damaged pancreas was resuscitated (4/5, 80%). It was suggested that 1 hr-preservation was not enough to synthesize ATP, which was essential to repair damaged cells, although vascular endothelial cells were maintained. Eight hr-preservation incurs endothelial cell damage although ATP tissue levels were maintained and consequently microcirculation was disturbed at reperfusion but OKY046 protects endothelial cells against preservation/reperfusion injury. As a consequence, the ischemically damaged pancreas was resuscitated. We conclude that short-term (3 to 8 hr) preservation at 20 degrees C by the two-layer method with OKY046 accelerates ATP synthesis, which is essential for repairing damaged cells and protects microvascular endothelial cells. This makes it possible to resuscitate the canine pancreas graft subjected to 90 min warm ischemia. This method holds promise for pancreas-kidney transplantation from cardiac arrest donors.

Animals↗
PubMed1996

Pancreas transplantation for diabetes mellitus.

Pancreas transplantation has become a viable option for the patient wi th insulin-dependent diabetes mellitus with progressive renal failure. The most common type of pancreas transplantation is a simultaneous pancreas and kidney transplantation performed from a single cadaver donor (SPK). The next most common is pancreas transplantation after successful kidney transplantation (PAK). A few centers are performing pancreas transplantation alone (PTA) in diabetic recipients without renal disease but who have significant complications from their diabetes. Pancreas transplantation is associated with a higher morbidity than kidney transplantation alone. Most pancreas transplantation centers report a significant increase in acute rejection, which can lead to increased hospitalization and risk of opportunistic infection. In addition, the early era of pancreas transplantation was associated with significant surgical complications. However, with bladder drainage of the pancreas exocrine secretions, the surgical complication rate has decreased significantly. Despite medical and surgical complications, the overall results for pancreas transplantation are excellent, with 1 -year graft survival of 75% for SPK transplantations and 48% for PAK and PTA transplant recipients. The effects of a pancreas transplantation on the secondary complications of diabetes have been studied extensively. Most studies have shown a modest improvement in secondary complications with the exception of diabetic retinopathy. The major benefit of pancreas transplantation appears to be enhanced quality of life for patients successfully transplanted. For these reasons, the Kidney-Pancreas Committee of the American Society of Transplant Physicians believes the current results of pancreas-kidney transplantation justify its use as a valid option for insulin-dependent diabetic transplant recipients.

Costs and Cost Analysis↗
PubMed1995

Cystoscopic biopsies in pancreaticoduodenal transplantation. Are duodenal biopsies indicative of pancreas dysfunction?

Tissue diagnosis of pancreas graft dysfunction is desirable. Bladder-drained pancreaticoduodenal transplants allow tissue diagnosis by cytoscopic biopsy procedures of the pancreas and duodenum. To assess the diagnostic utility of duodenal biopsies, we reviewed all cystoscopically obtained pancreas and duodenal biopsy tissues at our institution (July 1, 1989 through September 30, 1993). Adequate tissue for histologic examination was obtained from 75 biopsies in 58 recipients. Indications for cytoscopic biopsies were relative hypoamylasuria in 85%, hematuria in 6%, hyperamylasemia in 3%, and other causes in 6%. Duodenal specimens were available from 52 biopsies (25 with, and 27 without, concurrent pancreas biopsies). Of the 27 duodenal biopsies alone, 3 were diagnostic of rejection, 15 had features consistent with rejection, 6 were normal, 1 showed fibrosis, 1 showed necrosis, and 1 was ulcerated. Thus, two-thirds of the duodenal biopsies alone yielded clinically relevant information resulting in antirejection treatment. In 25 of the duodenal biopsies, pancreas tissue was also available (11 simultaneous pancreas-kidney, 9 pancreas transplant alone, and 5 pancreas after kidney recipients). Findings in both organs completely agreed in 9 (36%) of the biopsies. In 7 (28%), rejection was suggested or diagnosed in both organs, although the organs were discrepant with regard to the presence of vascular rejection (6 pancreas, 1 duodenum). In 2 (11%), minor nonrejection discrepant findings were present. Therefore, in 18 of 25 (72%) pancreas-duodenal biopsies, treatment would not have been different if only one graft had been biopsied. But in the other 7 (28%), treatment would have been different if only the organ with negative findings had been biopsied. In 6 cases (4 duodenal, 2 pancreas), rejection was seen in one organ but not the other. In 1 case, cytomegalovirus (CMV) inclusions were present in the duodenum, but the pancreas was normal. We conclude that (1) the duodenum and pancreas can reject independently of each other, and a negative biopsy does not preclude rejection of the other organ; (2) duodenal biopsies determined therapeutic decisions one-fifth of the time when both tissues were available for examination, and two-thirds of the time when only duodenal tissue was available; and (3) since cystoscopy allows easy access to the duodenum, both the pancreas and duodenum should be biopsied whenever possible; tissue samples of one organ alone are sufficient only with positive findings.

Adult↗
PubMed1996

A multicenter analysis of the first experience with FK506 for induction and rescue therapy after pancreas transplantation.

Between May 1, 1993 and April 5, 1995, 154 pancreas allograft recipients at 9 institutions were given FK506 posttransplant. Three groups were studied: (1) recipients given FK506 initially for induction and maintenance therapy (n = 82), (2) recipients switched to FK506 for antirejection or rescue therapy (n = 61), and (3) recipients converted to FK506 for other reasons (n = 11). Of 82 patients in the induction group, 7 (9%) had simultaneous bone marrow (BM) and pancreas-kidney (SPK-BM) transplants, 54 (66%) had SPK transplants without BM, 14 (17%) had pancreas transplants alone (PTA), and 7 (9%) had pancreas after previous kidney transplants (PAK). All but 1 recipient was given quadruple immunosuppression (anti-T cell agents plus azathioprine and prednisone) for induction. The median FK506 starting dose was 4 mg/day p.o.; the median average FK506 blood level, 12 ng/ml. The most common side effects were neurotoxicity (16%), nephrotoxicity (13%), and gastrointestinal toxicity (9%). New-onset diabetes mellitus requiring permanent insulin therapy did not occur. Of 61 transplants in the rescue group, 44 (72%) were SPK, 11 (18%) PTA, and 6 (10%) PAK. All but 3 (95%) of the recipients had been on cyclosporine-azathioprine-prednisone triple immunosuppression before substitution of FK506 for cyclosporine; 46% of the recipients had one, and 54% > or = 2, rejection episodes preconversion. The most common side effects were nephrotoxicity (25%), neurotoxicity (23%), and gastrointestinal toxicity (21%). Two recipients were reconverted to cyclosporine because of transient hyperglycemia, and one recipient is on insulin. In the induction group, patient survival at 6 months was 90% for SPK, 100% for PTA, and 100% for PAK. According to a matched-pair analysis, pancreas graft survival for SPK recipients at 6 months was 87% for FK506 versus 70% for cyclosporine recipients (P = 0.04); for PTA recipients, 84% versus 66% (P = n.s.); and for PAK recipients, 80% versus 14% (P = 0.11). When technical failures and death with functioning grafts were censored, pancreas graft survival remained significantly better in the FK506 group. The incidence of first reversible rejection episodes by 6 months in FK506 recipients was 35% for SPK, 40% for PTA, and 20% for PAK. Of 75 pancreas grafts, 64 are currently functioning; in 5 recipients the pancreas failed (1 from rejection); 6 recipients died with a functioning pancreas graft. There were 3 posttransplant lymphomas (all EBV-positive); 2 recipients died and 1 is alive after subtotal colectomy and transplant pancreatectomy. In the antirejection rescue group, patient survival rates at 6 months were 91% for SPK, 100% for PTA, and 80% for PAK (P = n.s.). Pancreas graft survival rates at 6 months were 90% for SPK, 72% for PTA, and 40% for PAK. The incidence of first reversible rejection episodes after conversion to FK506 at 6 months was 44% in SPK, 54% in PTA, and 50% in PAK. Of 61 pancreas grafts, 51 are currently functioning; in 7 recipients the pancreas failed (5 from rejection); 3 recipients died with a functioning graft. There were no posttransplant lymphomas in the rescue group. This multicenter survey shows that FK506 in pancreas transplantation is associated with (1) a low rate of graft loss from rejection when used for induction therapy, (2) a high rate of graft salvage when used for rescue or rejection therapy, and (3) a very low rate of new-onset insulin-dependent diabetes mellitus. These encouraging results are tarnished by 3 posttransplant lymphomas in the induction group; a possible explanation is overimmunosuppression, but further (randomized) studies are necessary to analyze the long-term risk-benefit ratio of FK506 after pancreas transplantation.

Adolescent↗
PubMed2006

Three dimensional reconstruction of the pancreas based on the virtual Chinese human--female number 1.

OBJECTIVE: To study the three dimensional (3D) reconstruction and 3D visualisation of the pancreas and create anatomy of the digitalised visual pancreas so as to construct a concrete basis for virtual operation and surgical operation on pancreas. METHODS: The digital imaging data of pancreas, duodenum, common bile duct, arteries, and veins were obtained from the virtual Chinese human--female 1 (VCH-F1). The image data were investigated and 380 images ascertained of pancreas picked up from images numbers 2617 to 2996. Finally, the images from number 2574 to 3017 were adopted to segment and processed using ACDSee and Photoshop so as to reconstruct 3D pancreas digitally. The data of pancreatic surfaces were transformed into Visualization Toolkit (VTK). The GUI program written with VC+ was used to display this VTK file and realise 3D visualisation of the pancreas. RESULTS: 3D reconstruction and visualisation of the pancreas and the peri-pancreatic structures (the duodenum, the common bile duct,the inferior vena cava, the portal vein vessels, the aorta, the coeliac trunk vessels) was successful. The 3D and visualised pancreas manifested itself with its complete structure as well as its adjacency to other tissues. CONCLUSION: The 3D reconstruction and 3D visualisation of the pancreas based on the digital data of VCH-F1 produces a digitally visualised pancreas, which promises a novel method for virtual operation on the pancreas, clinical operation on the pancreas, and anatomy of 3D visualised pancreas.

Arteries↗
PubMedDate not supplied

Lymphatic system of the pancreas.

A network of lymphatic vessels exists within the pancreas. The majority of vessels forming this network lie in the interlobular septa of connective tissue that subdivide the pancreas into lobes and lobules. Peripheral extensions of these interlobular lymphatics can be found within the lobules, but these intralobular lymphatics are relatively sparse. In the main, the intimate relationships of these internal pancreatic lymphatics are with the blood vessels and associated connective tissue. However in random areas, both intra- and interlobular lymphatics come into close relationship with acinar cells. Rarely are there lymphatics associated with islets of Langerhans, and then only where lymphatic vessels in connective tissue septa pass close to a pancreatic lobule that contains an islet at its periphery. Intra- and interlobular lymphatics are similar in structure. Both are thin walled having an endothelial lining and a delicate component of connective tissue. The pattern of interendothelial cell contacts and the sparsity of gaps between adjacent cells suggest that fluid movement through the intracytoplasmic system of vesicles is important in lymph formation in the pancreas. However intercellular transport is also likely to occur by a dynamic process involving fluid movement through dilatations between cells from interstitium to lymphatic lumen. Both exocrine and endocrine secretions of the pancreas may enter thoracic duct lymph directly in pancreatic lymph, but in normal circumstances this route of entry is not quantitatively important. The structural relationships between lymphatics and pancreatic parenchymal cells also make clear that lymph is not a significant pathway for their secretory products. Rather, the arrangement of lymphatics in the pancreas supports the view that lymph is primarily the drainage medium for substances that, for whatever reason, enter the interstitium. In addition, the low flow of lymph compared with that of plasma lends credence to the view that lymph is not a functionally important pathway for endocrine secretions from the pancreas to reach the blood. Both structural and functional evidence suggests that the proper functioning of the lymphatic system is of critical importance in the homeostasis of the pancreas. The lymphatic system of the pancreas, like that in other organs, is essential in the removal of excess fluid from the interstitium. In this sense, the lymphatics may be considered to serve as an overflow, protective, or safety system. When the system is inadequate or its capacity is exceeded, as in inflammation of the pancreas, exocrine secretions entering the interstitium are not cleared and the proteolytic enzymes cause major damage to the tissue. This, in turn, exacerbates the edema, accentuates the inability of lymphatics to drain the fluid, and results in further damage. The fibrosis that ensues damages the lymphatics either directly or through stricture of the surrounding connective tissue. In consequence, they become inadequate at an even earlier stage in subsequent attacks of inflammation and thereby predispose to chronic and recurrent pancreatitis. The larger interlobular lymphatics formed by the junction of their tributaries emerge upon the surface of the pancreas. There they travel primarily with blood vessels and stream toward a ring of lymph nodes that intimately surrounds the pancreas. A second system of nodes extensively involved in drainage from the pancreas is related to the front and sides of the aorta from the level of the celiac trunk to the origin of the superior mesenteric artery. This second set of nodes receives lymph either directly from the pancreas or indirectly from the first echelon of nodes that rings the organ. Although there is general agreement on the disposition of the groups within these sets of nodes, confusion results from the different classifications used by various authors. These classifications range from being purely descriptive, through an alpha and num

Animals↗
PubMed2001

Lessons learned from more than 1,000 pancreas transplants at a single institution.

OBJECTIVE: To determine outcome in diabetic pancreas transplant recipients according to risk factors and the surgical techniques and immunosuppressive protocols that evolved during a 33-year period at a single institution. SUMMARY BACKGROUND DATA: Insulin-dependent diabetes mellitus is associated with a high incidence of management problems and secondary complications. Clinical pancreas transplantation began at the University of Minnesota in 1966, initially with a high failure rate, but outcome improved in parallel with other organ transplants. The authors retrospectively analyzed the factors associated with the increased success rate of pancreas transplants. METHODS: From December 16, 1966, to March 31, 2000, the authors performed 1,194 pancreas transplants (111 from living donors; 191 retransplants): 498 simultaneous pancreas-kidney (SPK) and 1 simultaneous pancreas-liver transplant; 404 pancreas after kidney (PAK) transplants; and 291 pancreas transplants alone (PTA). The analyses were divided into five eras: era 0, 1966 to 1973 (n = 14), historical; era 1, 1978 to 1986 (n = 148), transition to cyclosporine for immunosuppression, multiple duct management techniques, and only solitary (PAK and PTA) transplants; era 2, 1986 to 1994 (n = 461), all categories (SPK, PAK, and PTA), predominantly bladder drainage for graft duct management, and primarily triple therapy (cyclosporine, azathioprine, and prednisone) for maintenance immunosuppression; era 3, 1994 to 1998 (n = 286), tacrolimus and mycophenolate mofetil used; and era 4, 1998 to 2000 (n = 275), use of daclizumab for induction immunosuppression, primarily enteric drainage for SPK transplants, pretransplant immunosuppression in candidates awaiting PTA. RESULTS: Patient and primary cadaver pancreas graft functional (insulin-independence) survival rates at 1 year by category and era were as follows: SPK, era 2 (n = 214) versus eras 3 and 4 combined (n = 212), 85% and 64% versus 92% and 79%, respectively; PAK, era 1 (n = 36) versus 2 (n = 61) versus 3 (n = 84) versus 4 (n = 92), 86% and 17%, 98% and 59%, 98% and 76%, and 98% and 81%, respectively; in PTA, era 1 (n = 36) versus 2 (n = 72) versus 3 (n = 30) versus 4 (n = 40), 77% and 31%, 99% and 50%, 90% and 67%, and 100% and 88%, respectively. In eras 3 and 4 combined for primary cadaver SPK transplants, pancreas graft survival rates were significantly higher with bladder drainage (n = 136) than enteric drainage (n = 70), 82% versus 74% at 1 year (P =.03). Increasing recipient age had an adverse effect on outcome only in SPK recipients. Vascular disease was common (in eras 3 and 4, 27% of SPK recipients had a pretransplant myocardial infarction and 40% had a coronary artery bypass); those with no vascular disease had significantly higher patient and graft survival rates in the SPK and PAK categories. Living donor segmental pancreas transplants were associated with higher technically successful graft survival rates in each era, predominately solitary (PAK and PTA) in eras 1 and 2 and SPK in eras 3 and 4. Diabetic secondary complications were ameliorated in some recipients, and quality of life studies showed significant gains after the transplant in all recipient categories. CONCLUSIONS: Patient and graft survival rates have significantly improved over time as surgical techniques and immunosuppressive protocols have evolved. Eventually, islet transplants will replace pancreas transplants for suitable candidates, but currently pancreas transplants can be applied and should be an option at all stages of diabetes. Early transplants are preferable for labile diabetes, but even patients with advanced complications can benefit.

Adolescent↗
PubMed2002

Role of CD4+ and CD8+ T cells in the rejection of concordant pancreas xenografts.

BACKGROUND: We studied the ability of CD4 and CD8 T cells to induce rejection of pancreas xenografts in a concordant combination using rat pancreas xenografts as donors and chemically induced diabetic mice as recipients. METHODS: Lewis rat (2 to 3 weeks old) pancreas xenografts were transplanted into streptozotocin (STZ)-induced diabetic mice. Lymphocyte proliferation and cytokine production were analyzed in vitro. All pancreas xenografts were assessed by functional (blood glucose) and histopathologic examinations. RESULTS: Lewis rat pancreas grafts were rejected within 10 to 13 days, with mononuclear cell infiltrate and tissue necrosis in STZ-induced diabetic mice. A predominant T cell receptor alphabeta -CD4 cell (on day 4) and T cell receptor alphabeta -CD8 cell (on day 8) infiltrate and IgM deposition were found in the pancreas xenografts after transplantation. Anti-CD4 (GK1.5), but not anti-CD8 (YTS169.4), monoclonal antibodies resulted in a prolonged survival of Lewis rat pancreas xenografts. Lewis pancreas xenografts were permanently accepted by CD4 knockout mice but not by CD8 knockout mice. The pancreas xenografts were acutely rejected with a mean survival time of 15.3 days in B cell-deficient mice (microMT/microMT). Transfer of CD4 but not CD8 spleen cells from naïve C57BL/6 mice into Rag2 mice led to acute rejection of transplanted pancreas xenografts. However, activated CD8 spleen cells elicited rejection of Lewis rat pancreas xenografts in SZT-induced diabetic mice. CONCLUSION: The current results show that CD4 T cells are necessary and sufficient for mediating the rejection of Lewis rat pancreas xenografts in STZ-induced diabetic mice. However, CD8 cells, when activated, can also induce acute rejection of concordant pancreas xenografts.

Animals↗
PubMed1991

Results of pancreas transplantation in the United States for 1987-90 from the United Network for Organ Sharing (UNOS) Registry with comparison to 1984-87 results.

An outcome analysis was performed on pancreas transplants in the United States reported to the United Network for Organ Sharing (UNOS) Registry from its inception on 1 October 1987 to 21 October 1990 (n=1021). These cases comprise nearly one-third of the 3082 pancreas transplants reported to the International Pancreas Transplant Registry (1819 U.S., 1263 non-U.S.) from 1 December 1966 to 31 December 1990, including 619 in 1990 (528 U.S., 91 non-U.S.). Nearly all pancreas transplants in the U.S. during the 1987-90 period were by the bladder-drainage (BD) technique (92%). The overall patient and pancreas graft actuarial survival rates were 92% and 72% at 1 year. Patient survival rates were similar in all recipient categories, but pancreas graft survival rates were significantly higher (p less than 0.001) in recipients of a simultaneous pancreas and kidney (SPK) transplant (n=883) than in recipients of a pancreas after a kidney (PAK, n=112) or a pancreas transplant alone (PTA, n=71), being 77%, 52%, and 54%, respectively, at 1 yr. Kidney graft survival at 1 yr in U.S. SPK recipients was 86%. Most grafts (81%) were preserved in University of Wisconsin (UW) solution, and more than half were stored greater than 12 hours, with no difference in outcome with increasing duration of storage. At 1 yr, functional survival rates were 72% for U.S. pancreas grafts stored for either less than 12 (n=439), 12-24 (n=422), or 24-30 h (n=42). For grafts stored greater than 30 h (n=8), the 1-yr functional survival rate was 50% (p=ns versus the other storage times). On univariate analysis, no effect of HLA antigen mismatching on outcome for 1987-90 U.S. cases could be discerned. The results in the UNOS Registry were compared to the results for U.S. cases in the International Pancreas Transplant Registry performed between 1 January 1984 and 30 September 1987. In all recipient categories the pancreas graft functional survival rates were significantly higher in the 1987-90 (UNOS) than in the 1984-87 (pre-UNOS) era. A Cox multivariate analysis of 1984-90 cases showed the relative risk for pancreas graft loss to be significantly less (p less than 0.05) with bladder-drainage, with simultaneous transplantation of the kidney, with use of UW solution for preservation, and with 0-1 HLA-A, B, DR or 0 HLA-DR mismatches.(ABSTRACT TRUNCATED AT 400 WORDS)

Graft Survival↗
PubMed2005

[The study of pancreas three-dimensional reconstruction based on the Virtual Chinese Human-Female No 1].

OBJECTIVE: To study the three-dimensional (3D) reconstruction and 3D visualization of the pancreas and create anatomy of the digitalized visual pancreas so as to construct a concrete basis for virtual operation and surgical operation on pancreas. METHODS: The digital imaging data of pancreas, duodenum, common bile duct, arteries and veins were obtained from the Virtual Chinese Human-Female 1 (VCH-F1) and processed using ACDSee and Photoshop so as to reconstruct 3D pancreas digitally and realize 3D visualization of pancreas. RESULTS: We successfully 3D reconstructed and visualized the pancreas and the peri-pancreatic structures: the duodenum, the common bile duct, the inferior vena cava, the portal vein vessels, the aorta, the ceoliac trunk vessels. The 3D and visualized pancreas manifested itself with its complete structure as well as its adjacency to other tissues. CONCLUSIONS: The 3D reconstruction and 3D visualization of the pancreas based on the digital data of VCH-F1 produces a digitally visualized pancreas, which promises us a novel method for virtual operation on pancreas, clinical operation on pancreas and anatomy of 3D visualized pancreas.

Anatomy, Cross-Sectional↗
PubMed1989

Early detection of rejection in pancreas transplantation.

A major dilemma in pancreas transplantation is the lack of reliable methods for the early detection of allograft rejection. Over a 26-mo period, 70 rejection episodes occurred in 36 patients (13 isolated-pancreas, 23 simultaneous pancreas-kidney recipients) with pancreaticoduodenocystostomy. A total of 300 radionuclide pancreas examinations were performed (mean 8.3/patient) utilizing 99mTc-labeled DTPA. Computer analysis generated a quantitative measure of blood flow to the allograft (technetium index, TI). Rejection episodes were defined as isolated pancreas, isolated kidney, or combined pancreas-kidney. Mean urinary amylase (UA) levels and TI during normal allograft function were 30,256 U/L and 0.57%, respectively, whereas levels heralding rejection were 6873 U/L and 0.39% (P less than .05). The treatment of rejection based on kidney dysfunction or combined pancreas-kidney dysfunction resulted in significantly higher graft salvage and a lower incidence of hyperglycemia compared with isolated-pancreas-allograft rejection. After therapy, a TI greater than 0.3% was associated with 95.9% graft survival, whereas levels less than 0.3% resulted in a 72.7% rate of graft loss (P less than .001). Similarly, pancreas allografts with a UA greater than 10,000 U/L had 92.2% functional survival, whereas levels less than 10,000 U/L resulted in a 53.3% rate of graft loss (P less than 0.001). Overall, reversal of rejection occurred in 80% of cases, with 10 pancreas and 2 kidney allografts lost due to rejection. Monitoring pancreas-allograft function by UA, TI, and renal function in simultaneous transplants allows for the timely diagnosis and successful treatment of pancreas-allograft rejection.

Adult↗
PubMed1995

Effect of blood group and HLA matching on pancreas graft survival with the use of UW solution.

Pancreas graft survival is influenced by various donor and recipient factors. Factors that have posed serious problems to pancreas transplantation have included the limited cold ischemia time, early graft thrombosis, and rejection. A limited cold ischemia time not only causes problems in terms of logistics but also implies limitations with regard to HLA matching and organ exchange. Between August 1988 and August 1989 we performed a prospective, nonrandomized European multicenter study to evaluate the effect of University of Wisconsin (UW) solution on pancreas graft survival. In addition, donor and recipient factors were collected and their influence on graft survival analyzed. Overall pancreas graft survival at 1 and 4 years was 67% and 59%, respectively (n = 62). When only simultaneous pancreas and kidney transplants were included, the graft survival was 70% and 63% at 1 and 4 years, respectively. The incidence of pancreas graft thrombosis was 8%. Cold ischemia time was not found to significantly influence pancreas graft survival even when it exceeded 12 h. Factors that did were HLA-DR matching, simultaneous pancreas and kidney transplantation versus pancreas transplantation alone, and ABO blood group matching. We feel that the use of UW solution for pancreas preservation has contributed to improved pancreas graft survival and has reduced early graft thrombosis despite much longer cold ischemia times of over 12 h. Given this and the significant effect of HLA and blood group matching, we conclude that more attention should be paid to preoperative matching and organ exchange in order to further improve pancreas graft survival.

Adenosine↗
PubMed1999

Living-donor pancreas and small-bowel transplantation.

BACKGROUND: In contrast to renal and liver transplantation, only a limited number of pancreas and intestinal live-donor transplants have so far been reported. PATIENTS: The vast majority of live segmental pancreas transplants have been performed at the University of Minnesota. From 1979 to 1993, a total of 78 solitary pancreas transplants--28 after kidney and 49 pancreas transplants alone--were performed and, from 1994 to August 1999, 27 simultaneous pancreas/kidney transplants. For the first intestinal transplant, a segment of ileum from the mother was used in Boston in 1964. In 1970, 170 cm of jejuno-ileum from a human leukocyte antigen (HLA)-identical sister was removed and transplanted in New York. In 1988, an intestinal transplant from a haplo-type-identical sister was performed at Kiel University, Germany. In the 1990s, a few more intestinal transplants from live donors were reported to the registry. RESULTS: No death occurred among pancreas or intestinal donors. Altogether, seven pancreas donors required splenectomy and several donors required drainage of abscesses or fluid collections. Three of the 78 pancreas donors and at least two of the 27 pancreas/kidney donors required insulin post-donation. Twenty-seven of the solitary segmental pancreas transplants failed for technical reasons. Graft survival of technically successful pancreas transplants was 68% after 1 year and 38% after 10 years. Patient and renal allograft survival of combined kidney/pancreas transplants after 1 year was 100%, while 1-year pancreas survival was 84%. The first recipient of a live-donor intestinal transplant died only 12 h after surgery. The second case lived for 79 days and was able to eat for 6 weeks. A patient transplanted in 1988 lived for 4 years mainly on oral nutrition. Many of the live-donor intestinal transplants carried out in the 1990s became long-term survivors. CONCLUSION: Pancreas and small-bowel transplantation using organs from live donors is possible in experienced centers, with no donor mortality and excellent survival rates for recipients and grafts. Since abnormal glucose tolerance post-donation cannot be excluded with certainty and since, for the time being, there is no pancreas or small-bowel shortage in Europe, live donation of these organs should be restricted mainly to highly sensitized patients with a cross-match-negative relative or HLA-identical donor-intestinal recipient combinations.

Diabetes Mellitus, Type 1↗
PubMed1981

Purification and characterization of a human pancreas-specific antigen.

A pancreas-specific antigen was identified by immunologic techniques and purified from saline extract of human pancreas. The purified pancreas-specific antigen was shown to be homogeneous by polyacrylamide gel electrophoresis under both denaturing and non-denaturing conditions. It had a molecular weight of 44000 as estimated by gel filtration or sodium dodecyl sulfate-gel electrophoresis, and a sedimentation coefficient of 3.4 S as analyzed by sucrose gradient centrifugation. Pancreas-specific antigen possessed an isoelectric point of 4.9 and migrated to alpha-beta region upon immunoelectrophoresis. By colorimetric assay procedures, pancreas-specific antigen exhibited no enzyme activity, such as amylase, protease, esterase, lipase, acid phosphatase, alkaline phosphatase peroxidase, deoxyribonuclease or ribonuclease. Immunoreactivity of pancreas-specific antigen was sensitive to proteolytic enzymes, perchloric acid and high temperature (70 degrees C, 10 min); but insensitive to neuraminidase or beta-glucosidase. Immunohistochemical staining revealed that pancreas-specific antigen was located in acinar cells of human pancreas. In addition, a higher concentration of pancreas-specific antigen was detected in pancreatic juice than in the saline extract of pancreas. This newly identified pancreas-specific antigen, therefore, may be a useful marker protein in physiological studies of pancreas and pancreatic secretion.

Animals↗
PubMed1991

Reversed-phase high-performance liquid chromatographic characterization of acetic acid extracts of the normal and the diabetic human pancreas.

The combination of a divinylbenzene-based reversed-phase (RP) column and acetic acid gradients in water as mobile phase described in the accompanying paper was used for characterizing the extractable polypeptides from the normal and the diabetic human pancreas. The pancreas was lyophilized, minced and extracted three times in 3 M acetic acid. After mechanical clarification, the raw extracts were applied directly to the RP column. Alternatively, the extracts were lyophilized and subjected to size-exclusion chromatography on Sephadex G-50 in 3 M acetic acid. Two fractions with mol. wt. greater than 6000 dalton (Peak I) or with mol. wt. less than or equal to 6000 dalton (Peak II) were obtained. The Sephadex G-50 size-exclusion chromatography and the RP-high-performance liquid chromatographic (HPLC) analyses of the crude extracts from a normal pancreas clearly demonstrated the weight distribution and differences between the exocrine pancreas (containing primarily the major digestive enzymes) and the endocrine pancreas (containing insulin, glucagon, etc.). RP-HPLC analyses of crude extracts from various normal pancreatic glands resulted in very similar UV profiles, whereas those from a number of individual diabetic glands differed. Chromatograms of acetic acid extracts from normal pancreata were similar when analysed before or after lyophilization, whereas lyophilization of acetic acid extracts of diabetic glands resulted in severely obscured chromatograms. RP-HPLC analyses clearly demonstrated several differences between the diabetic and the normal pancreas. In the crude extracts, the extractable proteins from the diabetic pancreas were shifted towards lower molecular weight and/or hydrophobicity. Further, a peak co-eluting with authentic, human insulin could be demonstrated in the raw extract and in the peak II material from the normal pancreas, whereas virtually no mass signal was seen in the UV-profiles of similar materials from the diabetic gland. This finding was further verified by insulin radioimmunoassay (RIA) performed on the isolated fractions after RP-HPLC of a crude extract from a normal and a diabetic pancreas. The insulin content in the diabetic pancreas was found to be ca. 1% of that in the normal pancreas. When authentic glucagon was added to crude extracts from a diabetic pancreas, a single component was found after immediate analysis, but after several hours at room temperature the glucagon was found to be degraded. Added insulin was stable under these conditions. Similar RP analyses were performed on a silica C4 column eluted with an acetonitrile gradient in trifluoroacetic acid.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetates↗