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PubMed2006

A quantitative analysis of the sensory and sympathetic innervation of the mouse pancreas.

Pain from pancreatitis or pancreatic cancer can be both chronic and severe although little is known about the mechanisms that generate and maintain this pain. To define the peripheral sensory and sympathetic fibers involved in transmitting and modulating pancreatic pain, immunohistochemistry and confocal microscopy were used to examine the sensory and sympathetic innervation of the head, body and tail of the normal mouse pancreas. Myelinated sensory fibers were labeled with an antibody raised against 200 kD neurofilament H (clone RT97), thinly myelinated and unmyelinated peptidergic sensory fibers were labeled with antibodies raised against calcitonin gene-related peptide (CGRP) and post-ganglionic sympathetic fibers were labeled with an antibody raised against tyrosine hydroxylase (TH). RT97, CGRP, and TH immunoreactive fibers were present in parenchyma of the head, body and tail of the pancreas with the relative density of both RT97 and CGRP expressing fibers being head>body>tail, whereas for TH, a relatively even distribution was observed. In all three regions of the pancreas, RT97 fibers were associated mainly with large blood vessels, the CGRP fibers were associated with the large- and medium-sized blood vessels and the TH were associated with the large- and medium-sized blood vessels as well as capillaries. In addition to this extensive set of sensory and sympathetic nerve fibers that terminate in the pancreas, there were large bundles of en passant nerve fibers in the dorsal region of the pancreas that expressed RT97 or CGRP and were associated with the superior mesenteric plexus. These data suggest the pancreas receives a significant sensory and sympathetic innervation. Understanding the factors and disease states that sensitize and/or directly excite the nerve fibers that terminate in the pancreas as well as those that are en passant may aid in the development of therapies that more effectively modulate the pain that frequently accompanies diseases of the pancreas, such as pancreatitis and pancreatic cancer.

Animals↗
PubMed2004

Immunohistochemical colocalization of type II angiotensin receptors with somatostatin in rat pancreas.

Earlier studies indicate that binding sites of type II angiotensin (AT2) receptors are detected all over the pancreas, as well as in the pancreatic exocrine cell line AR4-2J. However, lack of corresponding functional AT2 receptor responses can be detected in the exocrine pancreas. The aim of present study is to determine the protein expression of AT2 receptors in the pancreas by probing with an AT2 receptor-specific antibody, and to examine the role of AT2 receptors in the regulation of pancreatic endocrine hormone release. In Western protein analysis of adult rat tissues, expression of AT2 receptor-immunoreactive bands of 56, 68, and 78 kDa was detected in the adrenal, kidney, liver, salivary glands, and pancreas. In adult rat pancreas, strong immunoreactivity was detected on cells that were located at the outer region of Langerhans islets. Immunohistochemical studies indicated that AT2 receptors colocalized with somatostatin-producing cells in the endocrine pancreas. Consistent with the findings in adult pancreas, abundant expression of AT2 receptors was also detected in immortalized rat pancreatic endocrinal cells lines RIN-m and RIN-14B. To examine the role of AT2 receptors on somatostatin secretion in the pancreas, angiotensin-stimulated somatostatin release from pancreatic RIN-14B cells was studied by an enzyme immunoassay in the absence or presence of various subtype-selective angiotensin analogues. There was a basal release of somatostatin from RIN-14B cells at a rate of 8.72 +/- 4.21 ng/10(6) cells (n = 7). Angiotensin II (1 nM-10 microM) stimulated a biphasic somatostatin release in a dose-dependent manner with an apparent EC50 value of 49.3 +/- 25.9 nM (n = 5), and reached maximal release at 1 microM angiotensin II (982 +/- 147.34% over basal secretion; n = 5). Moreover, the AT2 receptor-selective angiotensin analogue, CGP42112, was 1000 times more potent than the AT1 receptor-selective angiotensin analogue, losartan, in inhibiting angiotensin II-stimulated somatostatin release. These results suggest that angiotensin may modulate pancreatic hormone release via regulation of somatostatin secretion.

Animals↗
PubMed2004

Simultaneous pancreas-kidney transplantation: short- and long-term results.

Simultaneous kidney and pancreas transplantation (SKPT) is the treatment of choice for a majority of type I diabetic patients with end-stage renal disease. With continual refinements in surgical technique and an evolving immunosuppressive arsenal, graft and patient survival have continually improved. The purpose of this study was to evaluate the short- and long-term results of SKPTs performed in 174 recipients from June 1985 to March 2003 including 37 segmental grafts with duct occlusion, 73 whole pancreas transplants with bladder diversion, and 64 whole pancreas grafts with enteric diversion. The series includes 160 cases with systemic drainage and 14 with portal drainage. In the segmental pancreas group, patient survival was 85%, 76%, and 53% with pancreas survival of 67%, 36%, and 15%, and kidney survival of 82%, 63%, and 15%, respectively, at 1, 5, and 10 years. Among the bladder diversion group, patient survival was 94%, 83%, and 73% pancreas survival 72%, 67%, and 65%, and kidney survival 89%, 78%, and 58%, respectively, 1, 5, and 10 years. Among the enter diversion group patient survival was 90% and 90% at 12 and 108 months, pancreas survival 80% and 65%, and kidney survival 85% and 85%, respectively. There were significant differences between curves of survival distribution according to the surgical technique applied for patients (P =.04), pancreas (P =.007), and kidney (P =.005). Based on the results from our study, the short- and long-term prognosis after SKPT is satisfactory, especially compared to the outcomes of long-term dialysis among patients with end-stage renal disease caused by type I diabetes.

Adult↗
PubMed2004

Experience with steroid-free maintenance immunosuppression in simultaneous pancreas-kidney transplantation.

INTRODUCTION: Steroid avoidance is possible in simultaneous pancreas-kidney transplantation with the use of newer immunosuppressive agents and induction therapy. We undertook a retrospective consecutive case review of patients treated at a university tertiary referral center. METHODS: Medical records of 44 consecutive patients receiving a pancreas-kidney transplant from November 2000 to September 2002 were reviewed. The immunosuppression protocol used in this series of patients consisted of thymoglobulin induction, combined with mycophenolate mofetil, tacrolimus, and sirolimus for maintenance immunosuppression. Steroids were used only while thymoglobulin was given and were typically discontinued by postoperative week 1. Main outcome measures included graft and patient survival rates, rejection rates of the kidney or pancreas, infection rates, and surgical complication rates. RESULTS: All 44 patients received a kidney-pancreas transplant with systemic venous anastomosis and enteric drainage of the pancreas. Patient kidney, and pancreas survival rates were 95.6%, 93.2%, and 88.7%, respectively. Biopsy-proven pancreas rejection rates at 1 and 6 months posttransplant were 2.3% and 2.3%. Kidney rejection rates at 1 and 6 months were 2.3% and 4.6%. Reasons for patient loss included one death from sepsis and one cardiovascular death. Reasons for kidney loss besides death included a thrombotic microangiopathy. Reasons for pancreas loss included three thromboses, one mild rejection/infection, and one duodenal segment leak with infection. All patients who have been free of rejection have been off steroids for the duration of follow-up. CONCLUSIONS: Newer immunosuppression protocols without maintenance steroids are possible with minimal rejection in the first 3 months and equivalent patient and graft survival rates compared with earlier protocols utilizing steroids. The potential beneficial long-term impact of steroid avoidance will require further study.

Cause of Death↗
PubMed2006

Serial peripheral blood cytotoxic lymphocyte gene expression measurements for prediction of pancreas transplant rejection.

Acute rejection after pancreas transplantation remains a significant problem and contributes to immunological graft loss. No clinical markers of pancreas rejection have been universally accepted. The purpose of this study was to investigate the use of genetic markers; granzyme B, perforin, and HLA-DRA in the peripheral blood of pancreas transplant recipients. These genes have been identified in renal and islet cell transplant recipients as noninvasive tools to predict acute rejection. Blood samples were collected weekly for up to 1 year posttransplant. Surveillance biopsies of the pancreas were scheduled at weeks 2, 4, 8, and 12 as part of the typical posttransplant protocol for patients with pancreas alone or pancreas after kidney transplantation. Exclusion criteria included a diagnosis of biopsy-proven chronic rejection alone, pancreatitis, or kidney rejection within 2 months after pancreas biopsy. Gene expression levels of granzyme B, perforin, and HLA-DRA were compared in patients with (n = 7) and without biopsy proven acute rejection (n = 7). Recipients with acute rejection showed increased expression of granzyme B, HLA-DRA, as well as perforin genes compared to patients without biopsy-proven rejection. In addition, we observed that elevation of these genes occurred as early as 4 weeks before the traditional biopsy diagnosis, while the recipients with no rejection showed no change in gene expression. Our data indicated that serial measurements of peripheral blood granzyme B, perforin, and HLA-DRA gene expression can be a useful tool to predict pancreas rejection in its earliest stage.

Antilymphocyte Serum↗
PubMed2003

Formation of the digestive system in zebrafish. II. Pancreas morphogenesis.

Recent studies have suggested that the zebrafish pancreas develops from a single pancreatic anlage, located on the dorsal aspect of the developing gut. However, using a transgenic zebrafish line that expresses GFP throughout the endoderm, we report that, in fact, two pancreatic anlagen join to form the pancreas. One anlage is located on the dorsal aspect of the developing gut and is present by 24 h postfertilization (hpf), the second anlage is located on the ventral aspect of the developing gut in a position anterior to the dorsal anlage and is present by 40 hpf. These two buds merge by 52 hpf to form the pancreas. Using heart and soul mutant embryos, in which the pancreatic anlagen most often do not fuse, we show that the posterior bud generates only endocrine tissue, while the anterior bud gives rise to the pancreatic duct and exocrine cells. Interestingly, at later stages, the anterior bud also gives rise to a small number of endocrine cells usually present near the pancreatic duct. Altogether, these studies show that in zebrafish, as in the other model systems analyzed to date, the pancreas arises from multiple buds. To analyze whether other features of pancreas development are conserved and investigate the influence of surrounding tissues on pancreas development, we examined the role of the vasculature in this process. Contrary to reports in other model systems, we find that, although vascular endothelium is in contact with the posterior bud throughout pancreas development, its absence in cloche mutant embryos does not appear to affect the early morphogenesis or differentiation of the pancreas.

Animals↗
PubMed2003

Experimental conversion of liver to pancreas.

BACKGROUND: The liver and the pancreas arise from adjacent regions of endoderm in embryonic development. Pdx1 is a key transcription factor that is essential for the development of the pancreas and is not expressed in the liver. The aim of this study was to determine whether a gene overexpression protocol based on Pdx1 would be able to cause conversion of liver to pancreas. RESULTS: We show that a modified form of Pdx1, carrying the VP16 transcriptional activation domain, can cause conversion of liver to pancreas, both in vivo and in vitro. Transgenic Xenopus tadpoles carrying the construct TTR-Xlhbox8-VP16:Elas-GFP were prepared. Xlhbox8 is the Xenopus homolog of Pdx1, the TTR (transthyretin) promoter directs expression to the liver, and the GFP is under the control of an elastase promoter and provides a real-time visible marker of pancreatic differentiation. In the transgenic tadpoles, part or all of the liver is converted to pancreas, containing both exocrine and endocrine cells, while liver differentiation products are lost from the regions converted to pancreas. The timing of events is such that the liver is differentiating by the time Xlhbox8-VP16 is expressed, so we consider this a transdifferentiation event rather than a reprogramming of embryonic development. Furthermore, this same construct will bring about transdifferentiation of human hepatocytes in culture, with formation of both exocrine and endocrine cells. CONCLUSIONS: We consider that the conversion of liver to pancreas could be the basis of a new type of therapy for insulin-dependent diabetes. Although expression of the transgene is transient, once the ectopic pancreas is established, it persists thereafter.

Animals↗
PubMed1997

The surgical risk of pancreas transplantation in the cyclosporine era: an overview.

BACKGROUND: Pancreas transplants are still associated with the highest surgical complication rate of all routinely performed solid organ transplants. To date, the impact of serious surgical complications in the cyclosporine era on perioperative patient morbidity, graft and patient survival, and hospital costs has not been analyzed in detail. STUDY DESIGN: We retrospectively studied surgical complications after 445 consecutive pancreas transplants (45% simultaneous pancreas-kidney [SPK], 24% pancreas after kidney [PAK], and 31% pancreas transplant alone [PTA]). Of these, 80% were primary transplants, 20% were retransplants. Cadaver donors were used in 92%, living related donors in 8%. To develop guidelines for their prevention and management, we studied the impact of significant surgical complications (intra-abdominal infections, vascular graft thrombosis, and anastomotic leak) requiring relaparotomy on graft and patient survival. RESULTS: Relaparotomy was required after 32% of all pancreas transplants (SPK: 36%, PAK: 25%, PTA: 16% [p = 0.04]). Perioperative mortality was 9%. Graft and patient survival rates were significantly lower for recipients with (versus without) relaparotomy. The most common procedures were drainage of intra-abdominal abscess with graft necrosectomy (50% of all relaparotomies) and transplant pancreatectomy (34%). The most common causes of relaparotomy were intra-abdominal infection, vascular graft thrombosis, and anastomotic leak. Intra-abdominal infection occurred in 20% (SPK: 18%, PAK: 24%, PTA: 20% [p = NS]). The rate was significantly higher for living related donor (42%) versus cadaver donor (18%) recipients and for those with enteric-drained (39%) versus bladder-drained (18%) transplants. Graft and patient survival rates were significantly lower for recipients with (versus without) intra-abdominal infection. Outcome was better after bacterial (versus fungal) infections. For SPK recipients, those not on dialysis before the transplant had significantly higher graft survival than those on dialysis. Vascular graft thrombosis occurred in 12% of all recipients. The rate was significantly higher for PAK (21%) than for PTA (10%) and SPK (9%) recipients. It was significantly lower for recipients of grafts with donor iliac Y-graft reconstruction (versus all other types of arterial reconstruction) and with right-sided (versus left-sided) graft placement. Of note, patient survival was not different for recipients with versus without vascular graft thrombosis. The incidence of anastomotic or duodenal stump leaks was 10%; of these recipients, 70% required relaparotomy. Patient and graft survival rates were no different for recipients with versus without leaks. CONCLUSIONS: Serious surgical complications occurred in 35% of pancreas recipients and had a significant impact on patient and graft survival. Based on multivariate risk factor analyses, we recommend the following: donors over 45 years and those dying of cerebrocardiovascular disease should not be used; recipients over 45 years and those with a history of cardiac disease should be considered for a kidney transplant alone (KTA); surgical technique for graft procurement, preparation, and implantation should be meticulous; right-sided implantation and arterial Y-graft reconstruction should be performed when possible, since they had the highest success rates; when complications require relaparotomy, the focus must switch from graft salvage to life preservation; and the threshold for pancreatectomy should be low. Diagnosis should be timely, and treatment and relaparotomy expeditious. These cornerstones of success should help decrease the risk of surgical complications and mortality after pancreas transplants.

Abdominal Abscess↗
PubMed1998

Results of a technique of pancreaticojejunostomy that optimizes blood supply to the pancreas.

BACKGROUND: Anastomotic failure after pancreaticojejunostomy is still a common problem. Failure rates have not decreased perceptibly in the past 3 decades. The neck of the pancreas is a vascular watershed between celiac and superior mesenteric arterial systems. Prior attempts to reduce anastomotic failure at pancreaticojejunostomy have not focused on issues related to blood supply of the pancreas. The aim of this study was to determine whether pancreaticojejunostomy performed using a technique that included optimization of blood supply to the pancreas, would result in a low anastomotic failure rate. METHODS: The technique was prospectively evaluated in 40 patients having pancreaticojejunostomy, 39 during pancreaticoduodenectomy and 1 after traumatic transection of the neck of the pancreas. Blood supply to the pancreatic neck was evaluated clinically and by Doppler techniques. When blood supply was considered marginal, the pancreas was re-resected 1.5-2.0 cm to the left, away from the vascular watershed. RESULTS: Blood supply at the cut margin of pancreas was judged as brisk in 24 patients and marginal in 16 patients. Resecting a segment of pancreas in these 16 patients resulted in brisk bleeding from the new cut margin in all but 1 patient who had an anomalous artery that had to be sacrificed for oncologic reasons. The only fistula in the series occurred in this patient. There were no intraabdominal abscesses. CONCLUSIONS: A technique that includes ensuring adequate blood supply to the pancreas can result in a very low rate of anastomotic failure.

Adolescent↗
PubMed1991

Effects of pancreas transplantation on postprandial glucose metabolism.

BACKGROUND: Because a pancreas allograft is placed in the pelvis, pancreas transplantation abolishes the normal gradient between portal-vein and peripheral-vein insulin concentrations and causes systemic hyperinsulinemia. Whether pancreas transplantation restores carbohydrate metabolism to normal is not known. METHODS: We studied seven patients with insulin-dependent diabetes mellitus after pancreas-kidney transplantation, seven nondiabetic patients after kidney transplantation (to control for immunosuppression), and eight normal subjects. Measurements were made after an overnight fast and after ingestion of a mixed meal. RESULTS: Although plasma glucose concentrations did not differ in the two transplant groups, plasma insulin concentrations were significantly higher in the diabetic pancreas-kidney recipients than in the nondiabetic kidney recipients, both before the meal (mean +/- SE, 102 +/- 15 vs. 53 +/- 6 pmol per liter; P less than 0.05) and afterward (123 +/- 22 vs. 61 +/- 6 nmol per liter per six hours; P less than 0.05). Plasma C-peptide concentrations were the same in both groups, indicating that hyperinsulinemia was due to decreased insulin clearance rather than increased insulin secretion. Despite drainage of the venous effluent from the transplanted pancreas into the systemic circulation, the values for splanchnic clearance of ingested glucose, suppression of hepatic glucose release, incorporation of carbon dioxide into glucose, stimulation of glucose oxidation, glucose uptake, and forearm glucose clearance were all similar in the transplant groups and differed minimally from the values in the normal group. The similar rates of glucose uptake in the presence of higher systemic insulin concentrations indicated that the extrahepatic tissues of the diabetic pancreas-kidney recipients were insulin-resistant. CONCLUSIONS: Despite systemic delivery of insulin, pancreas-kidney transplantation in patients with diabetes results in carbohydrate metabolism similar to that in nondiabetic subjects receiving the same immunosuppressive agents after kidney transplantation.

Adult↗
PubMed1993

Comparative changes between pancreas and pancreatic juice digestive enzyme contents during nutritional rehabilitation following severe protein malnutrition in the rat.

The relationship between digestive enzyme activities in the pancreas and pancreatic juice was studied in post-weaning rats fed on a low-protein diet (30 g cereal protein/kg) for 1 month and a refeeding balanced diet (235 g mixed protein/kg) for the following 3 months. A control group was fed on the balanced diet for 4 months. At the end of malnutrition and at various times of refeeding, activities of amylase (EC 3.2.1.1), trypsin (EC 3.4.21.4), chymotrypsin (EC 3.4.21.1), lipase (EC 3.1.1.3), phospholipase A2 (EC 3.1.1.4) and cholesterolesterase (EC 3.1.1.13) in pancreas and pancreatic juice were measured. Recovery of body and pancreas weights was obtained after 3 months of refeeding. Pancreas offered a higher resistance to the low-protein diet; a quicker recovery than that of the whole organism was observed during refeeding. Protein and RNA contents of pancreatic cells were depressed by protein depletion. At the end of refeeding, pancreatic and cell RNA contents were still depressed. In pancreas and pancreatic juice, protein depletion produced a decrease in enzyme activities, with the exception of phospholipase A2 and cholesterolesterase. During refeeding, activities were increased to various levels in pancreatic juice and pancreas. In pancreatic juice, a deficit in enzyme activities still prevailed at the end of refeeding. The retention thresholds (total activity in pancreas v. activity per h in pancreatic juice) of hydrolases were increased by malnutrition. They were all decreased by refeeding at various rates, but after 3 months of refeeding the thresholds were still markedly increased for all enzymes studied. After malnutrition and during refeeding, the dissociated enzyme activities in pancreas and pancreatic juice could be the expression of an alteration at different stages: synthesis, intracellular transport, storage mechanisms and secretion.

Amylases↗
PubMed1997

Molecular characterization of a pancreas-specific protein disulfide isomerase, PDIp.

A novel tissue-specific cDNA, PDIp, was previously isolated from human pancreas. It encodes a protein that is structurally and functionally related to protein disulfide isomerase (PDI). To compare the expression pattern of PDI and PDIp in human pancreas and liver tissues, we prepared rabbit polyclonal antiserum against a recombinant glutathione-S-transferase-coupled PDIp fusion protein. Western blot analysis revealed that pancreas expresses both PDI and PDIp, whereas liver only expresses PDI. Rabbit antiserum raised against recombinant PDIp immunostained specifically to the acinar cells of human pancreas. Treatment of PDIp with peptide:N-glycosidase F caused PDIp down shift in the NaDodSO4-PAGE gel, indicating that PDIp is a glycoprotein. A 2.0-kb message was detected from mouse pancreas using a human PDIp cDNA probe. Similarly, PDIp glycoprotein was detected in mouse pancreas extract by anti-human PDIp antiserum, suggesting that PDIp is highly conserved in human and mouse pancreas. From these studies, we conclude that the pancreas expresses two members of PDI and that PDIp is a glycoprotein specifically expressed in pancreatic acinar cells.

Animals↗
PubMed1988

Experience with simultaneous pancreas-kidney transplantation.

With refinements in surgical techniques and increased clinical experience, there has been a resurgence of interest in vascularized pancreas transplantation. From December 1986 to April 1988, 30 whole-organ vascularized pancreas transplants with pancreatico duodenocystostomy were performed simultaneously with renal transplantation. The recipient population consisted of 20 men and ten women, with a mean age of 34.7 years (range of 25-53 years). The mean duration of insulin-dependent diabetes mellitus (IDDM) was 22.6 years (range of 10-37 years). The mean pancreas preservation time was 8.7 hours (range 3-19 years). All patients were immediately insulin-independent. Simultaneous pancreas-kidney engraftment was performed to both iliac fossae via a lower midline incision (n = 28) or through a bilateral lower abdominal incision (n = 2). The mean operating time was 5.9 hours, and packed cell transfusion requirement was 1.3 units. The mean length of hospital stay was 27.4 days. Recipients averaged 2.3 admissions (1-7), with ten patients (34.4%) requiring only one hospital admission. Postoperative immunosuppression consisted of cyclosporine, prednisone, azathioprine, and Minnesota antilymphoblast globulin (MALG). A total of 49 episodes of rejection occurred in 26 patients. Actuarial patient survival rate at two years is 96.3%. The kidney and pancreas survival rates for the same time interval is 94.0% and 84.0%, respectively. Mean serum creatinine at present is 1.75 mg/dl. In conclusion, renal transplantation in concert with pancreas transplantation has a dramatic positive impact on pancreas allograft survival. Combined engraftment does not appear to jeopardize renal allograft functional survival. In view of these results, simultaneous pancreas-kidney transplantation appears to be the treatment of choice for Type I diabetic patients.

Adult↗
PubMed2001

Superiority of portal venous drainage over systemic venous drainage in pancreas transplantation: a retrospective study.

OBJECTIVE: To compare portal and systemic venous drainage of pancreas transplants and demonstrate an immunologic and survival superiority of portal venous drainage. SUMMARY BACKGROUND DATA: Traditionally, solitary pancreas transplants have been performed using systemic venous and bladder drainage, but more recently, the advantages of enteric drainage have been well documented. Although physiologic benefits for portal venous drainage have been described, the impact of portal venous drainage, especially with solitary pancreas transplants, has yet to be determined. METHODS: Since August 1995, 280 pancreas transplants with enteric duct drainage were analyzed. One hundred and seventeen were simultaneous pancreas and kidney (SPK), 63 with systemic venous drainage (SV) and 54 with portal venous drainage (PV). The remainder were solitary transplants; 97 pancreas after kidney (PAK; 42 SV and 55 PV) and 66 transplants alone (PTA; 26 SV and 40 PV). Immunosuppressive therapy was equivalent for both groups. RESULTS: The groups were similar with respect to recipient characteristics and HLA matching. Thirty-six month graft survival for all transplants was 79% for PV and 65% for SV (P =.008). By category, SPK graft survival was 74% for PV and 76% for SV, PAK graft survival was 70% for PV and 56% for SV, and PTA graft survival was 84% for PV and 50% for SV. The rate of at least one rejection episode was also significantly higher in the SV group. At 36 months, for all pancreas transplants, the rejection rate was 21% for PV and 52% for SV (P <.0001). For SPK, rejection rates were 9% for PV and 45% for SV. For PAK, rejection rates were 16% for PV and 65% for SV, and for PTA 36% for PV and 51% for SV. The rejection rates for kidneys following SPK were also lower in the PV group (26% versus 43% for SV). Furthermore, the grades of rejection were milder in PV for all transplants (P =.017). By multivariate analysis, portal venous drainage was the only parameter that significantly affected rejection. CONCLUSION: Graft survival and rejection is superior for PV. These clinical findings are consistent with published reports of experimentally induced portal tolerance and strongly argue that PV drainage should be the procedure of choice for pancreas transplantation.

Adult↗
PubMed1995

Use of ultrasound and cystoscopically guided pancreatic allograft biopsies and transabdominal renal allograft biopsies: safety and efficacy in kidney-pancreas transplant recipients.

The use of allograft biopsies to guide treatment after solid organ transplantation is a valuable tool in the detection and treatment of rejection. Prior development and use of the cystoscopically guided pancreatic allograft biopsy have allowed for more accurate and timely diagnosis of pancreatic allograft dysfunction, possibly contributing to our 1-year pancreas graft, renal allograft and patient survival rates of 87.1%, 88.5% and 96.8%, respectively. We reviewed our experience, examining efficacy and complication rates of pancreas and kidney biopsies in 31 cadaveric pancreas or combined kidney and pancreas transplants performed between June 1990 and February 1992 with at least 1 year of followup. There were 94 pancreas, 54 kidney and 53 duodenal mucosal biopsies in 29 evaluable patients. This biopsy technique uses a 24.5F side-viewing nephroscope to view the cystoduodenostomy, with the duodenum acting as a portal for biopsy needles into the pancreas. Pancreatic tissue is obtained with either an 18 gauge, 500 mm. Menghini aspiration/core needle or an 18 gauge, 500 mm. Roth core needle. Percutaneous renal allograft biopsies are performed independently or simultaneously with the pancreas biopsies using a 16 gauge spring loaded needle. Pancreas biopsies were prompted by clinical indications of rejection (decreased urinary amylase, increased serum amylase or increased serum creatinine) or by protocol (10, 21 and 40 days postoperatively). Among the biopsies 30% were required by protocol, of which 10 (36%) revealed abnormal pathological findings and 5 (18%) showed evidence of occult cellular rejection. Renal biopsies demonstrated rejection in 69% of the cases. Of simultaneous pancreas/kidney biopsies 33% revealed concomitant rejection. A total of 88 Menghini needles with 170 passes was used in 73 biopsy attempts, yielding 126 tissue cores with a 16% complication rate. A total of 41 Roth needles was used with 73 passes in 34 biopsy attempts, yielding 55 tissue cores with a complication rate of 21%. Complications included self-limited bleeding from the biopsy site in 13% of the cases, bleeding requiring clot evacuation and fulguration in 1% and asymptomatic hyperamylasemia in 12%. Renal biopsy complications included 1 arteriovenous fistula (2%). We conclude that ultrasound and cystoscopically guided pancreatic allograft biopsy and percutaneous renal allograft biopsies are safe and essential methods of obtaining tissue for histological diagnosis without serious sequelae. The Menghini and Roth needles in cystoscopically guided pancreatic allograft biopsy have similar yield and complication rates in obtaining pancreatic tissue, although they require different performance techniques. In some cases both needles are necessary and are complementary in obtaining adequate tissue.(ABSTRACT TRUNCATED AT 400 WORDS)

Abdomen↗
PubMed2004

Relationships between the autonomic nervous system and the pancreas including regulation of regeneration and apoptosis: recent developments.

Substantial new information has accumulated on the mechanisms of secretion, the development, and regulation of the gene expression, and the role of growth factors in the differentiation, growth, and regeneration of the pancreas. Many genes that are required for pancreas formation are active after birth and participate in endocrine and exocrine cell functions. Although the factors that normally regulate the proliferation of the pancreas largely remain elusive, several factors to influence the growth have been identified. It was also reported that the pancreas was sensitive to a number of apoptotic stimuli. The autonomic nervous system influences many of the functions of the body, including the pancreas. In fact, the parasympathetic nervous system and the sympathetic nervous system have opposing effects on insulin secretion from islet beta cells; feeding-induced parasympathetic neural activity to the pancreas stimulates insulin secretion, whereas stress-induced sympathetic neural activity to the pancreas inhibits insulin secretion. Moreover, it has been reported that the autonomic nervous system is one of the important factors that regulate pancreatic regeneration and stimulate the carcinogenesis. The present review focuses on the relationships between the autonomic nervous system and the pancreas, and furthermore, presents evidence of the autonomic nervous system-related pancreatic regeneration and carcinogenesis.

Animals↗
PubMed1990

A simple method for the release of islets by controlled collagenase digestion of the human pancreas.

A simple technique for the controlled collagenase digestion of the human pancreas is described. The pancreas is distended with collagenase, and a biopsy taken and divided into 5 pieces that are placed in Universals containing minimal essential medium and dithizone at 39 degrees C. The pancreas itself is incubated in MEM at 39 degrees C. Starting at 5 min and at intervals thereafter, a Universal is removed from the water bath, shaken for 30 sec, and the contents examined by microscopy. As soon as free cleaved islets are seen, the pancreas is placed into one compartment of a kidney-bowl divided in half by a 1-mm mesh. The pancreas is gently teased apart and fluid digest in the empty half of the bowl aspirated and passed through a 500-micron mesh into ice-cold MEM containing 20% newborn calf serum. This process is repeated until the digestion process has ceased. Using this technique on 20 consecutive pancreata, median wt. (range) 53.9 (45.2-72.9) g, we have counted 131,672 (43,516-400,000) islets in the digest, equivalent to 2394 (715-8000) islets/g pancreas. The volume of islet tissue in the digest was 299 (26-1341) mm3 equivalent to 5.81 (0.36-26.81) mm3/g pancreas. In conclusion, we have found this simple technique to be an effective method for the controlled collagenase digestion of the human pancreas.

Adolescent↗
PubMed1993

Differences in rejection grading after simultaneous pancreas and kidney transplantation in pigs.

Clinical observations suggest that recipients of multiorgan transplants from the same donor can have disparate immunological reactions to each organ. We studied this phenomenon in 36 diabetic (streptozotocin-induced), bilaterally nephrectomized immunosuppressed (cyclosporine, azathioprine, prednisone) pig recipients of simultaneous (same donor) pancreas (bladder drained) and kidney allografts by grading the histological intensity of rejection in biopsies of each organ at defined intervals posttransplant. Graft function was monitored by plasma glucose (PG) and urine amylase (UA) for the pancreas and serum creatinine (Cr) for the kidney. Interstitial rejection was graded as absent, mild, moderate, and severe in, respectively, 8%, 25%, 42%, and 5% of pancreas vs. 4%, 12%, 27%, and 50% of kidney biopsies at 1 week; and 0%, 43%, 29%, and 29% of pancreases vs. 10%, 0%, 30%, and 60% of kidneys at two weeks. Although the distribution of grades was similar in the two organs (P > 0.1), the grade of rejection for each pair at 1 week (n = 24) was discordant in 75% (41% differed by one and 35% by > or = 2 grades) and at 2 weeks (n = 7) in 57% (29% by 1 and 29% by > or = 2 grades). The inability to use the severity of interstitial rejection in one organ to predict the findings in the other is exemplified by the fact that for the two pancreases without interstitial rejection at one week, the corresponding kidney showed moderate or severe rejection, and for the 1 kidney without rejection the corresponding pancreas showed moderate rejection. Vascular rejection grades (absent, mild, moderate, severe) also showed a similar distribution for the pancreas (57%, 30%, 9%, 4%) vs. kidney (56%, 30%, 0%, 13%) at 1 week, and at 2 weeks (57%, 29%, 0%, and 14% for the pancreas vs. 78%, 11%, 0%, and 11% for the kidney) (P > or = 0.64). However, the grading of vascular rejection in organ pairs was dyssynchronous in 51% at 1 week (n = 22) and 29% at 2 weeks (n = 7). No vascular rejection in the pancreas with rejection in the kidney was seen in 5 pairs at 1 week (23%) and 0 at 2 weeks (0%), while no rejection in the kidney with rejection in the pancreas was seen in 5 pairs at 1 week (23%) and 2 pairs at 2 weeks (29%).(ABSTRACT TRUNCATED AT 400 WORDS)

Amylases↗