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PubMed1998

Pancreatic carcinoma in remnant pancreas after pancreatectomy for mucinous cystadenoma.

There are very few benign or malignant diseases which arise in the remnant pancreas after pancreatectomy. Pancreatic carcinoma in the remnant pancreas after pylorus preserving pancreatoduodenectomy (PpPD) for mucinous cystadenoma in a 66-year-old Japanese man is reported in this paper. The patient underwent PpPD for a mucinous cystadenoma in the pancreatic head 39 months prior to the present operation. The surgical margins of the PpPD specimen were free from atypical cells. Follow-up ultrasonography revealed a hypoechoic lesion in the body of the remnant pancreas. Magnetic resonance cholangiopancreatography (MRCP) revealed a stenosis of the main pancreatic duct, with upstream dilatation in the remnant pancreas. Segmental resection of the remnant pancreas, splenectomy, pancreaticojejunostomy and intraoperative radiotherapy were performed under the diagnosis of pancreatic carcinoma of the remnant pancreas. Final histopathological diagnosis was adenocarcinoma of the pancreas. There were no malignant cystic components. The present pancreatic carcinoma was regarded as independent of the previous mucinous cystadenoma. Postoperative radiation therapy and chemotherapy were added. He is doing well 20 months after the second operation although diabetes mellitus has slightly deteriorated. In this communication, we would like to recommend that clinicians should constantly be on guard against the development of pancreatic carcinoma even in the remnant pancreas after pancreatectomy for mucinous cystadenoma.

Adenocarcinoma↗
PubMed1992

The mechanism of action of the two-layer (Euro-Collins' solution/perfluorochemical) cold storage method in canine pancreas preservation.

To clarify the mechanism of action of a two-layer [Euro-Collins' solution (EC)/perfluorochemical (PFC)] cold storage method in the preservation of the pancreas, pancreatic viability and tissue concentrations of adenosine triphosphate (ATP) were examined in the canine model of pancreatic autotransplantation after preservation for 24 and 48 h by simple cold storage in EC (group 1), the two-layer, EC/PFC, method (group 2) and the two-layer, EC+2, 4 dinitrophenol (DNP)/PFC, method (group 3). DNP is an uncoupler of oxidative phosphorylation. Maintenance of normoglycemia for at least 5 days after transplantation was considered a successful preservation. After preservation for 24 h, the functional success rates of groups 1, 2 and 3 were 100% (4/4), 100% (5/5) and 80% (4/5) respectively. One of five dogs in group 3 died of a cause unrelated to the pancreas. ATP tissue concentrations in group 2 were significantly higher than in group 1 (7.47 +/- 0.47 micromol/g dry weight vs 1.41 +/- 0.53 micromol/g dry weight, P < 0.01) and ATP tissue concentrations in group 3 were significantly lower than in group 2 (1.25 +/- 0.37 micromol/g dry weight vs 7.47 +/- 0.47 micromol/g dry weight, P < 0.01). It was apparent that ATP was not an essential factor for successful 24-hour preservation of the canine pancreas in EC because all the pancreatic grafts except one of five grafts in group 3 remained viable after preservation for 24 h, regardless of ATP tissue concentrations. On the other hand, after preservation for 48 h, the functional success rates for groups 1, 2 and 3 were 0% (0/4), 100% (4/4) and 0% (0/3) respectively. ATP tissue concentrations in group 2 were significantly higher than in group 1 (7.91 +/- 1.21 micromol/g dry weight vs 1.21 +/- 0.31 micromol/g dry weight, P < 0.01) and ATP tissue concentrations in group 3 were significantly lower than in group 2 (0.61 +/- 0.07 micromol/g dry weight vs 7.91 +/- 1.21 micromol/g dry weight, P < 0.01). It was clear that preservation of the pancreas for 48 h was unsuccessful by simple cold storage in EC (group 1) and the two-layer method (group 2) made preservation for 48 h possible by increasing ATP tissue concentrations. However, DNP (group 3) inhibited the synthesis of ATP and the effectiveness of the two-layer method for 48-hour preservation of the pancreas. It was clear that maintenance of high ATP tissue concentrations during preservation was essential for the successful preservation of the canine pancreas in EC by the two-layer method for more than 48 h. We concluded that an adequate supply of oxygen to the pancreas during preservation by the two-layer method led to sufficient production of ATP to maintain cellular integrity and permitted the improvement of pancreatic preservation.

Animals↗
PubMed2005

[Pancreas removal by external teams].

Combined pancreas and kidney transplantation is an established procedure for terminal or preterminal, uremic, type 1 diabetics. The current procurement technique allows simultaneous recovery of liver and pancreas. One problem is the assessment of organ quality. It remains unclear how many pancreas organs must be withdrawn during back-table preparation. Between June 1994 and December 2003, 271 pancreas transplantations were performed at our transplant centre. Two hundred sixty-two (89.7%) pancreas grafts were harvested by teams which were not part of the transplant team. Twenty-one (8.0%) grafts were discharged for transplantation at the time of back-table preparation. Liposis of the graft and critical vessel situations were the main reasons for withdrawal. Two kidney grafts were not usable for transplantation, and 92% of the pancreas grafts were. This demonstrates the high standard of pancreas procurement in the Eurotransplant region.

Adipose Tissue↗
PubMed2005

Percutaneous ultrasound-guided pancreas allograft biopsy: a single-center experience.

Percutaneous ultrasound-guided pancreas allograft biopsy is the preferred technique for evaluating pancreas allograft rejection. Experience from large centers has shown it to be safe and effective. We report our experience with 120 percutaneous allograft biopsies performed at a single center. Biopsy tissue was obtained in 54 patients. Thirty-three patients received simultaneous pancreas and kidney transplants, 14 received isolated pancreas transplants, and 7 received a pancreas transplant after kidney transplantation. Biopsies were performed by pancreas transplantation surgeons with the assistance of radiologists under ultrasound guidance using an Acuson XP 128/10 ultrasound machine. One hundred twenty allograft biopsies were performed in 54 patients. Twenty-seven (50%) patients underwent multiple biopsies. In 102 (85%) biopsies the specimens were adequate for examination. Eighteen (15%) biopsy samples had no pancreatic tissue and showed surrounding fat and small bowel. 1 (1.8%) patient bleeding developed that required transfusion of 3 units of packed red blood cells, but no surgical intervention was necessary. One (1.8%) patient had a pancreatic fistula, which healed with nonoperative management. Biochemical evidence of pancreatitis was noted in 5 (9.2%) patients, but none of these patients had clinical signs of pancreatitis. Percutaneous ultrasound-guided pancreas allograft biopsy is a safe procedure with a low complication rate and a high tissue yield for histopathologic examination.

Biopsy↗
PubMed2004

Pancreas graft thrombosis: is there a role for trypsin.

PURPOSE: Thrombosis of the pancreas graft is the main cause of early graft loss in pancreas transplantation. We investigated whether hypercoagulability develops locally in the pancreas and contributes to thrombosis formation because of ischemia or reperfusion injury. It was further hypothesized that this might be induced by excessive intravascular trypsin activity. METHODS: Ten Patients undergoing pancreas transplantation were studied. In addition to the standard operation a 14 French catheter was inserted in the distal part of the splenic vein of the pancreas graft. After reperfusion blood samples were drawn simultaneously from the splenic vein of the pancreas graft (local samples) and the radial artery (systemic samples) at 0,1,2,5,10,30, and 60 minutes after reperfusion. RESULTS: After reperfusion a progressive hypercoagulability developed locally in the pancreas as seen by an increase of thrombin-antithrombin complexes and only a transient increase of plasmin-antiplasmin complexes. In addition antithrombin 3 and protein c decreased systemically. The alterations seem not to be triggered by trypsin because trypsin activity locally remained low despite trypsinogen release and activation as assessed by trypsinogen activation peptides. CONCLUSION: Local hypercoagulability might contribute to the development of graft thrombosis, however, the mechanism seems not to be related to ectopic trypsin activation.

Antithrombins↗
PubMed1987

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.

Animals↗
PubMed1996

Experimental hyperacute rejection in pancreas allotransplants.

A model of sensitization by intraperitoneal lymph node inoculation was developed to test the hypothesis that hyperacute rejection (HAR) could occur in sensitized recipients of vascularized pancreas allografts. Ten pairs of outbred mongrel dogs that were lymphocytotoxic cross-match assay negative were inoculated with homogenized lymph nodes on either three or four occasions at fortnightly intervals before renal transplantation. A renal allograft from the same donor was used to test the HAR response and to further enhance sensitization by rejection of a vascularized organ. Pancreas transplants were performed 2 weeks later, with biopsies of the graft and blood samples taken at 0, 10, 20, and 30 min and then at 30-min intervals until the grafts were no longer viable. All renal and pancreas grafts were rejected in a classical hyperacute pattern. Within 4 min of revascularization of the pancreas, central lobular hemorrhage and vascular congestion appeared, followed by general edema. Histology demonstrated parallel changes of edema, vascular congestion, necrosis, hemorrhage, and leukocytic infiltrate, which all preceded graft infarction. A sharp decline in both arterial and venous white blood cell count and platelets occurred within 10 min of revascularization with initial sequestration and subsequent release of platelets from the graft (P=0.02). In summary, HAR of the allografted pancreas can be observed by the surgeon within minutes of revascularization, with predictable macroscopic and microscopic changes. This study supports the use of routine lymphocytotoxic cross-match tests for all recipients of pancreas transplants and implies that particular care is warranted in regraft pancreas allograft recipients.

Acute Disease↗
PubMed1996

Extending the margin of safety of preservation period for resuscitation of ischemically damaged pancreas during preservation using the two-layer (University of Wisconsin solution/perfluorochemical) method at 20 degrees C with thromboxane A2 synthesis inhibitor OKY046.

We have shown that 5-hr preservation using the two-layer (University of Wisconsin solution/perfluorochemical) method at 20 degrees C allows ATP synthesis and makes it possible to resuscitate a canine pancreas subjected to 90 min of warm ischemia. However, 8 hr of preservation using this method caused a disturbance of vascular microcirculation and did not resuscitate the grafts. The aim of this study was to examine the effect of thromboxane A2 synthesis inhibitor OKY046 on vascular endothelial cells and ATP tissue levels of canine pancreas during preservation using the two-layer (University of Wisconsin solution/perfluorochemical) method at 20 degrees C, and vascular microcirculation and pancreas viability after transplantation. Graft viability was judged by graft survival following autotransplantation. ATP tissue levels were measured by high-performance liquid chromatography at the end of preservation. Viability of the vascular endothelial cells was judged using nuclear trypan blue uptake of the graft after preservation. Pancreatic tissue perfusion was measured using an H2 clearance technique after reperfusion. Pancreas grafts subjected to 90 min of warm ischemia were not viable (0/5). However, 5-hr preservation made it possible to recover the pancreas (5/5); 8-hr preservation was not successful (0/3). ATP tissue levels after 5-hr and 8-hr preservation were 9.40+/-2.09 and 7.37+/-1.06 micromol/g dry weight, respectively, and OKY046 did not affect ATP synthesis during 8-hr preservation (8.44+/-0.92 micromol/g dry weight). The percentage of nuclear trypan blue uptake of endothelial cells in 8-hr-preserved grafts was 37.6+/-11.6% and was significantly higher than the value in 5-hr-preserved grafts (5.0+/-3.0%; P<0.01). However, OKY046 significantly reduced trypan blue uptake in 8-hr-preserved grafts (8.2+/-3.6%; P<0.01). Pancreatic tissue perfusion in 8-hr-preserved grafts after 2 hr of reperfusion was 28.5+/-7.5 ml/min/100 g, and was significantly lower than the value in 5-hr-preserved grafts (57.1+/-4.4 ml/ min/100 g; P<0.01), but OKY046 dramatically improved pancreatic tissue perfusion (97.1+/-14.6 ml/min/100 g; P<0.01). As a consequence, 8-hr-preserved grafts were resuscitated (4/5). We conclude that OKY046 protects the vascular endothelium during preservation by the two-layer method at 20 degrees C and consequently improves vascular microcirculation on reperfusion. Together with ATP synthesis, which is essential for repairing damaged cells, the canine pancreas graft subjected to 90 min of warm ischemia is resuscitated during 8-hr preservation by the two-layer method at 20 degrees C. This method holds promise for pancreas-kidney transplantation from cardiac arrest donors.

Adenosine↗
PubMed2004

Initial experience using histidine-tryptophan-ketoglutarate solution in clinical pancreas transplantation.

BACKGROUND: The colloid-based University of Wisconsin (UW) preservation solution has been used extensively in clinical pancreas transplantation. Experimental studies support the use of the crystalloid-based histidine-tryptophan-ketoglutarate (HTK) preservation solution for this purpose. AIM: We report our initial experience with HTK for pancreas allograft preservation and compare this to a contemporary experience with UW solution in conventional multiorgan deceased donors (<50 yr). MATERIALS AND METHODS: Retrospectively collected information on 33 pancreas transplants between September 2001 and October 2002 were analyzed for early graft function and complications up to 30 d after procurement and storage in either HTK or UW solutions. During multi-organ recovery, either UW solution (4-5 L) or HTK solution (8-10 L) was used for aortic perfusion and subsequent back-table flush and storage. Exocrine drainage of 31 pancreas allografts was enteric, while the bladder was used for drainage in two cases. Patient outcomes were analyzed according to the preservation solution used. Sixteen pancreata were used in combination with a kidney allograft (SPK), seven were used in patients after prior kidney transplantation (PAK), while 10 were used in patients who were not in renal failure (PTA). RESULTS: The UW group consisted of 17 patients (10 SPK, three PAK, four PTA) with a mean donor age of 29.5 +/- 10.7, and a mean cold ischemia time of 15.1 +/- 2.1 h. The mean post-transplant pancreas and kidney function on days 1 and 10 were amylase (315 and 99 IU/L), lipase (1727 and 346 IU/L), glucose (121 and 100 mg/dL) and creatinine (5.01 and 1.77 mg/dL). Patient and graft survival was 100% at 1-month post transplant. In the HTK group there were 16 patients (six SPK, four PAK, six PTA) with a mean donor age 21.9 +/- 5.7 and a mean cold ischemia time 14.0 +/- 1.3 h. The mean post-transplant pancreas and kidney function on days 1 and 10 were amylase (588 and 126 IU/L), lipase (4711 and 441 IU/L), glucose (97 and 109 mg/dL) and creatinine (5.28 and 2.42 mg/dL). Patient survival was 100% while graft survival was 94% at 1-month post-transplant. CONCLUSIONS: Early graft function and complications are comparable with HTK and UW solutions for pancreas allograft preservation.

Adenosine↗
PubMed1980

Effect of atropine on secretion from intact and transplanted pancreas in dog.

In dogs with a fistula of the intact pancreas and a transplanted portion of pancreas, we studied the effect of atropine on the pancreatic secretory response to intravenous caerulein and to intestinal perfusion with tryptophan, both given with a secretin background. Atropine (50 micrograms . kg-1 given as an intravenous bolus injection followed by 20 micrograms . kg-1 . h-1 iv infusion) depressed bicarbonate and protein secretion from intact pancreas during stimulation by secretin alone (250 ng . kg-1 . h-1) but did not suppress the increment in bicarbonate secretion in response to caerulein or tryptophan given against the secretin background. In intact pancreas, atropine suppressed protein secretion in response to tryptophan but not in response to caerulein. Atropine had no significant effect on the secretion of bicarbonate and protein from transplanted pancreas in response to secretin, caerulein, or tryptophan. Thus, the only significant effect of atropine on bicarbonate and protein secretion from intact and transplanted pancreas in response to intravenous caerulein or intraduodenal tryptophan, both given against a background of secretin, was inhibition of the protein response to tryptophan in the intact pancreas. These findings are compatible with the hypothesis that pancreatic protein secretion in response to intraduodenal tryptophan is mediated in part by a cholinergic enteropancreatic reflex.

Animals↗
PubMed1997

Correlation of the arterial resistive index in pancreas transplants of patients with transplant rejection.

OBJECTIVE: This study was undertaken to determine whether arterial resistive indexes (RIs) in pancreas transplants correlate with biopsy-proven transplant rejection. MATERIALS AND METHODS: We retrospectively reviewed arterial RIs in pancreas transplants for all patients who underwent Doppler sonography within 1 week before transcystoscopic or percutaneous biopsy of pancreas transplants. RIs were correlated with type and degree of rejection in the 20 transplants for which biopsies provided sufficient tissue for diagnosis. Three patients were subsequently eliminated from the study because of significant intervening therapy between sonography and biopsy. RESULTS: The nine transplants with no evidence of rejection had a mean arterial RI of 0.64 (range, 0.49-0.80). The six transplants with acute mild or moderate rejection had a mean RI of 0.67 (range, 0.56-0.73). The two transplants with acute severe rejection had a mean RI of 0.85 (range, 0.80-0.90). We found no statistically significant difference between arterial RIs in pancreas transplants of patients with acute mild or acute moderate rejection and those with no evidence of rejection. CONCLUSION: Arterial RIs of pancreas transplants do not differentiate between acute mild or acute moderate rejection and absence of rejection. The higher mean value of arterial RIs in pancreas transplants with acute severe rejection suggests that elevated arterial RIs are sensitive, but not specific, for revealing acute severe rejection of pancreas transplants. However, our study data are limited, and a larger sample size is necessary to draw statistically significant conclusions.

Adult↗
PubMed2004

Evaluation of the viability and energy metabolism of canine pancreas graft subjected to significant warm ischemia damage during preservation by UW solution cold storage method.

AIM: To evaluate the viability and energy metabolism of long warm ischemically damaged pancreas during preservation by the UW solution cold storage method. METHODS: The pancreas grafts subjected to 30-120 min warm ischemia were preserved by the UW solution cold storage method for 24 h. The tissue concentrations of adenine nucleotides (AN) and adenosine triphosphate (ATP) and total adenine nucleotides (TAN) were determined by using high performance liquid chromatography (HPLC) and the viability of the pancreas graft was tested in the canine model of segmental pancreas autotransplantation. RESULTS: The functional success rates of pancreas grafts of groups after 30 min, 60 min, 90 min, 120 min of warm ischemia were 100%, 100%, 67.7%, 0%, respectively. There was an excellent correlation between the posttransplant viability and tissue concentration of ATP and TAN at the end of preservation. CONCLUSION: The UW solution cold storage method was effective for functional recovery of the pancreas suffering 60-min warm ischemia. The tissue concentration of ATP and TAN at the end of 24 h preservation by the UW solution cold storage method would predict the posttransplant outcome of pancreas graft subjected to significant warm ischemia.

Adenosine↗
PubMed1997

The mutual benefit role of liver and pancreas in combined transplantation.

The present study observed the mutual benefit role of liver and pancreas in combined hepaticopancreatic transplantation in rats. The results indicated that pancreas, when transplanted with liver, could survive for a significant long time (13.4 +/- 1.01 days) than it transplanted alone (9.2 +/- 1.14 days) (P < 0.05, t test). The interstitial rejection was mild and its rejection grade was significantly different from that of pancreas transplanted alone (P < 0.05, X2 test). The liver, when transplanted with pancreas, regenerated with strong competence and contact structure morphologically compared with liver transplanted alone. We think that pancreas could be immunologically protected against rejection and liver can be nutritionalized by pancreas in combined liver and pancreas transplantation.

Animals↗
PubMed1992

Evaluation of the viability and energy metabolism of ischemically damaged canine pancreas during preservation by the two-layer (University of Wisconsin solution/perfluorochemical) cold storage method.

We evaluated the viability and energy metabolism of ischemically damaged pancreas during preservation by the two-layer (University of Wisconsin solution (UW)/perfluorochemical (PFC)) cold storage method. The pancreas grafts subjected to 60-120 min warm ischemia were preserved by the two-layer (UW/PFC) cold storage method for 24 hours (group 3), a simple cold storage in UW for 24 hours (group 2) or without preservation (control) (group 1). The tissue concentration of adenine nucleotides (ANs) were determined using high performance liquid chromatography (HPLC) and the viability of the pancreas graft was tested in the canine model of segmental pancreas autotransplantation. The functional success rates of pancreas grafts of groups 1, 2 and 3 after 60 min of warm ischemia were 5/5 (100%), 4/5 (80%) and 5/5 (100%). After 90 min warm ischemia, the success rates of groups 1, 2 and 3 were 0/5 (0%), 0/5 (0%) and 5/5 (100%) respectively. Only the two-layer method (group 3) was effective for functional recovery of the pancreas suffered 90 min warm ischemia. However, after more than 105 min, the result was 0/5 (0%) in group 3. In groups 1 and 2, there was no correlation between the posttransplant viability and tissue concentration of ANs and energy charge potential (ECP) at the end of preservation. However, in group 3, there was an excellent correlation between the posttransplant viability and tissue concentration of adenosine triphosphate (ATP) and total adenine nucleotides (TAN) at the end of preservation. We conclude that tissue concentration of ATP and TAN at the end of 24 hour preservation by the two-layer (UW/PFC) method will predict the posttransplant outcome of pancreas graft subjected to significant warm ischemia.

Adenine Nucleotides↗
PubMed1976

Transplantation of the pancreas.

A procedure was developed in the laboratory for pancreatic allotransplantation in pancreatectomized dogs. Dogs with such grafts have survived for many months when treated with azathioprene and prednisone to prevent rejection. Contrary to usual beliefs, the pancreas is not unduly sensitive to total ischemia since it has been possible to successfully preserve a canine pancreas in vitro with hypothermia for periods up to 24 hours. Such preserved pancreas' have then been allotransplanted into pancreatectomized dogs with survival of the dogs for long periods. We have now done pancreaticoduodenal allotransplantation in 13 patients with juvenile onset diabetes mellitus. Nine of these patients also had renal failure and received simultaneously a renal allograft taken from the same cadaver. In all but one of these patients the pancreas functioned immediately. Two patients with juvenile onset diabetes mellitus and severe retinopathy but without terminal renal failure have received pancreaticoduodenal allografts alone. In both of these patients the pancreas functioned immediately but problems with the duodenum necessitated the removal of the pancreaticoduodenal allograft which did not show signs of rejection. As a result of the findings of increased sensitivity of the kidney and duodenum to rejection we have now modified our technique to transplant the pancreas alone. This technique was used in one patient with juvenile onset diabetes mellitus and severe retinopathy. Her renal function was only moderately reduced. The pancreatic allograft initially functioned normally but then was removed at 28 days because of clinical signs of rejection of the pancreas which were confirmed by the microscopic findings. Despite the promise of islet-cell transplantation, no long term functioning allografts have resulted in animals or man. Thus we need to continue with whole organ pancreatic allografts by various techniques if diabetes mellitus is to be controlled.

Adult↗
PubMed1999

Lifelong prevention of mesangial enlargement by whole pancreas transplantation in rats with diabetes mellitus.

BACKGROUND: Mesangial enlargement (ME) is one of the hallmark lesions of diabetic nephropathy and plays a major role in diabetic renal failure. Conventional treatment of type 1 diabetes mellitus with insulin injections, diet, and medications has often failed to prevent development and progression of ME, presumably because of difficulty in achieving tight metabolic control. Although many pancreas transplantations have been done in patients with type 1 diabetes mellitus, there is insufficient information about their influence on ME or other diabetic lesions that are responsible for its morbidity and mortality. HYPOTHESIS: Whole pancreas transplantation will prevent diabetic ME throughout the life of the rat with alloxan-induced diabetes mellitus. DESIGN: Mesangial enlargement was studied for 28 months by a highly reproducible quantitative morphologic method in 55 nondiabetic control rats, 57 control rats with alloxan-induced diabetes mellitus, 97 diabetic rats that received a pancreaticoduodenal isograft shortly after the induction of diabetes mellitus, and 126 diabetic rats that received a duct-ligated pancreas isograft shortly after the induction of diabetes mellitus. Mesangial enlargement was determined by measuring the area occupied by camera lucida tracings of the mesangium using an electronic planimeter connected to a computer. RESULTS: Monthly metabolic studies showed that whole pancreas transplantation maintained very tight metabolic control of diabetes mellitus. Alloxan-induced diabetes mellitus produced progressive accumulation of mesangial matrix and progressive enlargement of all elements of the mesangium during the study. The 2 types of whole pancreas transplants provided lifelong protection against abnormal ME (P = .006). CONCLUSIONS: These results, combined with our previous finding of lifelong prevention of abnormal glomerular capillary basement membrane thickening, demonstrate that whole pancreas transplantation performed early in the course of alloxan-induced diabetes mellitus is capable of preventing diabetic kidney lesions. Moreover, these results suggest that whole pancreas transplants might be useful preventive therapy in patients with diabetes mellitus who undergo kidney transplantation for renal failure, in whom recurrence of nephropathy often develops in the transplanted kidney.

Animals↗
PubMed2003

Expression and misexpression of members of the FGF and TGFbeta families of growth factors in the developing mouse pancreas.

We have performed a high-capacity, semiquantitative, reverse transcriptase-polymerase chain reaction screen for expression of fibroblast growth factor (FGF) and transforming growth factor beta (TGFbeta) family genes as well as their cognate receptors. By using cDNA prepared from embryonic day 12 to postnatal day 0 embryonic mouse pancreas, we have identified several factors potentially involved in the development of the endocrine pancreas. We find high-level early expression of TGFbeta-1 and -2, and constitutive expression of TGFbeta-3 and their receptors. Of the Inhibin/Activin members, we found exclusively Inhibin-alpha and Activin-betaB to be expressed, and the BMP family was represented by BMP4, BMP5, and BMP7. The predominant forms of the BMP and Activin type II receptors were ActR-IIB and BMPR-II and of the type I receptors, BMPR-1A and -1B were the highest expressed. FGF1, FGF7, FGF9, FGF10, FGF11, and FGF18 were also expressed in the pancreas at varying time points and levels, as well as FGF receptor forms FGFR1b, FGFR1c, FGFR2b, FGFR2c, FGFR3b, and FGFR4. To gain insight into the biological function, we misexpressed members of these families in the pancreas by using the early pancreas promoter Pdx1. Misexpression of FGF4 results in disruption of the pancreas morphology with epithelial structures interspersed in stroma tissue. The endocrine compartment was reduced to scattered single cells, and the exocrine consisted of unbranched ductal epithelia with acinar structures budding off. In contrast, misexpression of BMP-6 resulted in complete agenesis of the pancreas and reduced the size of the stomach and spleen dramatically and caused fusion of the liver and duodenum.

Animals↗
PubMed2003

Magnetic resonance imaging of the pancreas and pancreatic tumors in a mouse orthotopic model of human cancer.

Pancreatic adenocarcinoma has a rising incidence and a very poor survival rate. To develop new treatment strategies, extensive research is performed on animal models of pancreatic cancer. Orthotopic pancreatic tumors models, where the tumor is implanted into the pancreas, resemble the human disease more closely than subcutaneous tumor models, yet are difficult to monitor. In our study we report a magnetic resonance imaging (MRI) approach to visualize the pancreas in mice and to monitor orthotopically implanted pancreatic tumors. An MRI scanner was used to image normal murine pancreas and the pancreas of mice implanted with a human pancreatic adenocarcinoma cell line. Gadolinium (Gd)-DTPA-enhanced T1- and T2-weighted standard sequences were used with the objective to identify the pancreas and to monitor the growth of orthotopic tumors during 30 days. The pancreas as well as the implanted tumors could be easily identified using MRI. On T2-weighted images, the implanted tumors were easily visualized at the implantation side with high signal intensity. After application of a contrast agent, the tumors showed an enhancement. Heterogeneities within the tumor could be delineated, corresponding to histology, and the size of the tumor could be measured precisely. MR serves as a noninvasive high-resolution image modality to monitor murine pancreas as well as size, growth and even areas of heterogeneity in orthotopic pancreatic tumors.

Adenocarcinoma↗