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PubMed2003

Chronic rejection: the next major challenge for pancreas transplant recipients.

OBJECTIVE: With newer immunosuppressive agents, acute rejection and graft loss resulting from acute rejection have become less common for pancreas transplant recipients. As long-term graft survival rates have improved, an increasing number of grafts are being lost to chronic rejection (CR). We studied the incidence of CR and identified risk factors. METHODS: We retrospectively analyzed all cadaver pancreas transplants performed at the University of Minnesota between June 19, 1994, and December 31, 2002. We determined the causes of graft loss, the incidence of graft loss to CR and, using multivariate techniques, the major risk factors for CR. RESULTS: A total of 914 cadaver pancreas transplants were performed in the following three categories: simultaneous pancreas-kidney (SPK) (n=321), pancreas after kidney (PAK) (n=389), and pancreas transplant alone (PTA) (n=204). The mean recipient age was 41.3 years and the mean donor age was 30.1 years. Of the 914 pancreas grafts, 643 (70.3%) continue to function (mean length of follow-up, 39 months). The most common cause of graft loss was technical failure, accounting for 118 (12.9%) of the failed grafts. The second most common cause was CR, accounting for 80 (8.8%) of the failed grafts. The incidence of graft loss to CR was highest for PTA (n=23 [11.3%]) and PAK (n=45 [11.6%]) recipients and lowest for SPK recipients (n=12 [3.7%]) (P=0.002). By multivariate analysis, the most significant risk factors for graft loss to CR were a previous episode of acute rejection (relative risk [RR]=4.41, P<0.0001), an isolated (vs. simultaneous) transplant (PAK or PTA [vs. SPK], RR=3.02, P=0.002), cytomegalovirus infection posttransplant (RR=2.41, P=0.001), a retransplant (versus primary transplant) (RR=2.27, P=0.004), and one or two (vs. zero) antigen mismatches at the B loci (RR=1.68, P=0.04). CONCLUSIONS: As short-term pancreas transplant results improve and as isolated (PAK or PTA) pancreas transplants gain in popularity, CR will become increasingly common as a cause of pancreas graft loss.

Acute Disease↗
PubMed2004

Technical failures after pancreas transplants: why grafts fail and the risk factors--a multivariate analysis.

BACKGROUND: Technical failure (TF) rates remain high after pancreas transplants; while rates have decreased over the last decade, more than 10% of all pancreas grafts continue to be lost due to technical reasons. We performed a multivariate analysis to determine causes and risk factors for TF of pancreas grafts. RESULTS: Between 1994 and 2003, 937 pancreas transplants were performed at our center in the following transplant categories: simultaneous pancreas-kidney (SPK) (n=327), pancreas after kidney (PAK) (n=399), and pancreas transplant alone (PTA) (n=211). Of these, 123 (13.1%) grafts were lost due to technical reasons (thrombosis, leaks, infections). TF rates were higher for SPK (15.3%) versus PAK (12.2%) or PTA (11.4%), though this was not statistically significant. Thrombosis accounted for 52.0% of all TFs. Other causes were infections (18.7%), pancreatitis (20.3%), leaks (6.5%), and bleeding (2.4%). Thrombosis was the most common cause for TF in all three transplant categories. By multivariate analysis, the following were significant risk factors for TF of the graft: recipient body mass index (BMI) >30 kg/m (relative risk [RR]=2.42, P=0.0003), preservation time >24 hr (1.87, P=0.04), cause of donor death other than trauma (RR=1.58, P=0.04), enteric versus bladder drainage (1.68, P=0.06), and donor BMI >30 kg/m (1.66, P=0.06). Not significant were donor or recipient age, a retransplant, and the category of transplant. CONCLUSIONS: TFs remain significant after pancreas transplants. In SPK recipients, TF represents the most common cause of pancreas graft loss. For isolated pancreas transplants, TF is second only to rejection as a cause of graft loss. Increased preservation times and donor or recipient obesity seem to be risk factors. Minimizing these risks factors would be important to try to decrease TF.

Adult↗
PubMed2005

Posttransplant lymphoproliferative disorder in pancreas transplantation: a single-center experience.

BACKGROUND: Posttransplant lymphoproliferative disorder (PTLD) is a rare, serious complication of transplantation. The characteristics and associations of this disease in pancreas recipients have not been extensively studied. METHODS: From January 1988 through December 2002, 787 pancreas and 569 kidney-pancreas transplants were performed at our institution. Eighteen pancreas recipients developed polymorphic PTLD or malignant lymphoma. Data on clinical course, organ involvement, molecular characteristics, and association with immunosuppression and recent cytomegalovirus (CMV) infection were compiled from the institutional transplant database. Patient survival was compared to recipients of liver and kidney transplants at the same center by using Kaplan-Meier analysis. RESULTS: The 5-year cumulative incidence of PTLD in simultaneous pancreas-kidney, pancreas after kidney, and pancreas transplant alone recipients was 2.5%, 1.2%, and 1.0%, respectively (P = 0.23). A noticeably, but not significantly, higher cumulative incidence was seen in the more recent era since 1995 (2.1% vs. 0.9%, P = 0.15). PTLD in pancreas recipients carried a worse prognosis than in liver or kidney for recipients B-cell, early-onset, and Epstein Barr virus-positive lesions. PTLD was more aggressive in pancreas recipients, with a higher stage at presentation and a trend to more bone marrow involvement. There appeared to be a tendency toward association with recent CMV infection. Since 1995, PTLD recipients have had a lower exposure to antilymphocyte preparations (25 +/- 5 vs. 10 +/- 0.8)(P < 0.05). CONCLUSIONS: PTLD in pancreas recipients remains a rare but aggressive disease, and carries a worse prognosis in comparison to other transplant recipients. These heavily immunosuppressed patients, who often face multiple transplants, may be at greater risk; CMV infection may play an antecedent role.

Adult↗
PubMed2006

Alemtuzumab induction and tacrolimus monotherapy in pancreas transplantation: One- and two-year outcomes.

BACKGROUND: Alemtuzumab (Campath-1H) induction with tacrolimus monotherapy has been shown to provide effective immunosuppression for kidney, liver, lung, and small bowel transplantation. This drug combination was evaluated in pancreas transplant recipients. METHODS: Sixty consecutive pancreas transplants (30 simultaneous pancreas-kidney, 20 pancreas after kidney, and 10 pancreas alone) were carried out under this protocol between July 2003 to January 2005. The mean follow-up was 22 months (range 17-33). RESULTS: One-year patient, pancreas, and kidney allograft survival were 95%, 93%, and 90%, respectively. With 22 months follow-up, patient, pancreas, and kidney survival were 94%, 89%, and 87%, respectively. The rejection rate was 30% (18/60), with four patients (7%) experiencing steroid-resistant rejection. Major infection occurred in three (5%) patients resulting in two (3.3%) deaths from disseminated histoplasmosis and a herpes virus infection. One patient with cryptococcal meningitis was successfully treated. Seven (11.7%) patients experienced cytomegalovirus infection, all of whom responded to treatment with ganciclovir. One (1.7%) case of polymorphic posttransplant lymphoproliferative disease was seen, which regressed with a temporary discontinuation of tacrolimus and high-dose ganciclovir. The mean serum creatinine of the 30 simultaneous pancreas-kidney transplants at one year posttransplant was 1.37+/-0.33 mg/ml. The preexisting creatinine in pancreas after kidney transplants was not adversely affected by this immunosuppressive protocol. CONCLUSION: A single dose of perioperative alemtuzumab followed by daily tacrolimus monotherapy provides effective immunosuppression for pancreas transplantation, but the optimal use of this drug combination is not yet clear.

Alemtuzumab↗
PubMed2005

Pancreatic tumor associated with pancreas divisum.

BACKGROUND: Although there has been considerable controversy regarding pancreas divisum and pancreatitis, little discussion of this has taken place. The purpose of the present paper was to investigate the relationship between these two conditions. METHODS: A retrospective investigation was undertaken of pancreatic tumors associated with pancreas divisum, in 650 cases of pancreatic carcinoma, 80 cases of intraductal papillary mucinous tumor of the pancreas and 32 cases of pancreas divisum. RESULTS: Of these 32 cases, four (12.5%) were associated with pancreatic tumor: pancreatic carcinoma (n = 3) and intraductal papillary mucinous tumor (n = 1). All tumors developed from the dorsal pancreas of pancreas divisum. Periductal and interlobular fibrosis detected in the non-carcinomatous pancreas of the margin of distal pancreatectomy implied that chronic dorsal pancreatitis associated with pancreas divisum preceded carcinoma. CONCLUSIONS: Pancreatic tumors were detected in 12.5% of cases of pancreas divisum. In pancreas divisum, longstanding pancreatic duct obstruction caused by relative stenosis of the minor duodenal papilla might be a factor promoting oncogenesis.

Adenocarcinoma↗
PubMed1979

Insulin secretion by isolated perfused rat and mouse pancreas.

A method for isolation and perfusion of a pancreas preparation consisting of pancreas, stomach, proximal duodenum, and spleen is described. Basic characteristics of regulation of insulin secretion from the perfused pancreas isolated from rats, albino mice, obese mice (ob/ob), and black mice were identical. Viability and stability of the pancreas preparation during perfusion were maintained as documented by measurements of oxygen consumption of the pancreas preparation, perfusion pressure, and pH of the perfusion medium. The insulin-secretory capacity of the pancreas of different animal species was compared. Insulin secretion by the perfused rat and obese (ob/ob) mouse pancreas was much more potent than that by the pancreas of lean albino and lean black mice. D-Glucose-induced insulin secretion from the pancreas was decreased after fasting of the animals and was dependent on glucose concentration and presence of calcium in the perfusion medium. D-Glyceraldehyde, tolbutamide, D-mannose, dihydroxyacetone, L-leucine, and L-arginine also induced insulin secretion from the pancreas. D-Fructose, D-galactose, L-glucose, 3-O-methyl-D-glucose, N-acetylglucosamine, D-xylose, D,L-glyceric acid, pyruvate, L-lactate, and theophylline did not provoke insulin secretion.

Animals↗
PubMed1985

Ontogeny of immunoreactive insulin in the fetal bovine pancreas.

The aim of this study was to characterize the development of immunoreactive insulin (IRI) in the fetal bovine pancreas. Pancreatic IRI was acid extracted, and both pancreatic and serum IRI were quantitated by RIA. The amount of pancreatic IRI per wet tissue wt in first trimester fetuses was similar to that in the adult animal (8.2 +/- 0.7 and 5.9 +/- 1.7 U/g pancreas, respectively). IRI increased progressively during gestation, attaining 39.2 +/- 6.5 U/g pancreas in the third trimester, 7-fold higher than that in the adult. When pancreatic IRI concentrations were standardized for protein content of the extracts, a decrease was noted between the midsecond and third trimesters. This is most likely the result of dilution of the endocrine portion of the pancreas by the rapidly growing exocrine pancreas. IRI was also detectable in fetal sera from all three trimesters. In contrast to the profile for pancreatic concentrations of IRI, serum concentrations remained constant throughout gestation at approximately 20 microU/ml. Poly(A+)RNA was isolated from adult and fetal pancreata, and the relative levels of preproinsulin mRNA were assessed by DNA/RNA filter hybridization. There was a 2- to 3-fold increase in the relative level of preproinsulin mRNA in fetal pancreata between the first and second trimesters which was maintained through the third trimester. In the adult pancreas, preproinsulin mRNA levels were similar to those in the first trimester fetus. This profile for the ontogeny of pancreatic preproinsulin mRNA was similar to that for pancreatic IRI (units per pancreas) during fetal maturation. We conclude that in the bovine fetus: the endocrine pancreas synthesizes IRI during all three trimesters of development; pancreatic (units per g pancreas), but not serum, concentrations of IRI increase progressively as development proceeds; and the ontogeny of preproinsulin mRNA is paralleled by that of pancreatic IRI (units per pancreas).

Animals↗
PubMed1996

Effect of pancreas transplantation on free fatty acid metabolism in uremic IDDM patients.

To assess the effect of pancreas transplantation on free fatty acid (FFA) and glucose metabolism, we studied seven uremic IDDM patients (HbA1c 9.1%), nine IDDM patients after combined kidney-pancreas transplantation (HbA1c 5.8%), seven patients with chronic uveitis (HbA1c 5.6%), and nine normal control subjects (HbA1c 5.5%) by means of the [3(- 3)H]glucose and [1(-14)C]palmitate infusion techniques combined with indirect calorimetry and euglycemic insulin clamp. In the postabsorptive state, pancreas-transplant patients had similar plasma glucose and FFA concentrations and non-statistically different rates of hepatic glucose production (HGP) and FFA turnover, while demonstrating a reduced rate of FFA oxidation (42 +/- 5 vs. 73 +/- 10 micromol x m-2 x min-1; P < 0.05) compared with control subjects. After 180 min of tracer equilibration, all subjects underwent a low-dose (100 min, 8 mU x m-2 x min-1) followed by a high-dose (100 min, 40 mU x m-2 x min-1) euglycemic insulin infusion. During insulin infusion, pancreas-transplant patients showed a greater inhibition of FFA concentration (609 +/- 76 to 58 +/- 15 micromol/l) compared with healthy subjects (681 +/- 90 to 187 +/- 25 micromol/l; P < 0.01 vs. pancreas-transplant patients). FFA turnover and oxidation rates during both low-dose and high-dose insulin infusions were lower in pancreas-transplant patients compared with healthy subjects (P < 0.03 and P < 0.01, for turnover and oxidation, respectively). Uremic IDDM patients demonstration altered basal and insulin-mediated glucose metabolism. Pancreas transplantation normalized only insulin-mediated glucose oxidation, leaving the stimulation of non-oxidative glucose disposal still markedly defective. In conclusion, patients after pancreas transplantation have normal basal FFA turnover and reduced basal FFA oxidation rates. During hyperinsulinemia, pancreas-transplant patients show a normal inhibition of FFA turnover and FFA oxidation. Insulin-mediated glucose metabolism remained abnormal after pancreas transplantation. Our findings may be related to the effect of chronic immunosuppressive therapy on glucose and FFA metabolism.

Adult↗
PubMed1992

Health-related quality of life outcomes of pancreas transplant recipients.

The health status and quality of life outcomes of 131 patients who were 1 to 11 years post-pancreas transplant were studied. Patients were compared based on the current status of their pancreas graft, i.e. whether or not their grafts were successful in maintaining an insulin-independent state, and according to recipient category (pancreas alone vs kidney and pancreas). For this study, quality of life was defined as patients' perceptions of their well-being and ability to function in six areas: physical and mental health, social functioning, role (work and home) functioning, overall health perceptions, and physical pain. Patient self-report questions from the Medical Outcome Study were used to provide a score scaled from 0 to 100, for each area. Health status was assessed by sick days, hospitalizations, and emergency room visits. Patients with a successful pancreas graft (N = 65) reported significantly more positive health perceptions (51.9 vs 28.9), less pain (33.9 vs 45.3), and greater ability to function socially (84.9 vs 71.3) than did patients whose pancreas grafts were not successful. In addition, patients with successful pancreas grafts rated their ability to perform routine activities as nearer to normal on the Karnofsky Index (2.82 vs 3.63) and were more likely to view themselves as healthier since the pancreas transplant than were patients whose pancreas grafts were not successful. These effects persisted after statistical adjustment for recipient category and case-mix factors of age, sex, education, and length of time since pancreas transplant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2000

Difference of rejection in single versus combined pancreas and kidney transplantation in rats.

OBJECTIVE: To investigate the difference of rejection in single versus combined pancreas and kidney transplantation in rats. METHODS: Allograft models including simultaneous pancreas and kidney (SPK) transplant and pancreas or kidney transplant alone were established in SD-Wistar rats, rejections of pancreas and kidney in different models were compared morphologically and functionally. RESULTS: Mean survival time (MST) of pancreas was significantly prolonged in SPK than in pancreas transplant alone (PTA) (11.5 days vs. 9.2 days, P < 0.05). Incidence of interstitial pancreatic rejection at gade II and grade III was much obvious in PTA than in SPK (42.9% vs. 12.5% at grade II and 28.6% vs 6.3% at grade II , P < 0.05). No significant difference was found in MST between SPK and kidney transplant alone( KTA). Administration of cyclosporine A prolonged the MST of pancreas and kidney, without altering the tendency stated above. CONCLUSIONS: In SPK, the function of pancreas is protected by kidney hence the severity of rejection is reduced, whereas the function of kidney is not protected by pancreas. It suggests that different organs differ in immunoallergization and immunoregulation, and immune response tend to attack organs with greater immunoactivity, those organs with minor one could be protected. Cyclosporine A is effective on prolonging the MST of pancreas and kidney.

Animals↗
PubMed1992

Factors leading to improved outcome following pancreas transplantation--the influence of immunosuppression and HLA matching.

The results of pancreas transplantation continue to improve and do not appear to have plateaued worldwide. In the United States, pancreas graft survival rates are now similar or better than those for other organ transplants, particularly when the pancreas is transplanted simultaneously with a kidney. Since 1987, more than three fourths of uremic recipients of simultaneous pancreas and kidney grafts are insulin independent and dialysis-free more than 1 year after transplantation. Although there is room for improvement in the results of solitary pancreas transplants, more than half of these patients are insulin independent at 1 year. A successful pancreas transplant results in near normalization of glucose metabolism and lowers glycosylated hemoglobin to normal levels. While a successful pancreas transplant may not elevate all diabetic patients to the level of health and function of the general population, pancreas transplant recipients report a significantly better quality of life than do those patients who remain diabetic. As the success rate of pancreas transplantation continues to improve, this treatment should be considered as a means for restoring a normal glucose level in type I diabetic patients before the development of advanced, disabling complications of the disease. Our recommendation for an approach to minimizing the antirejection response and maximizing graft survival rates in pancreas transplant recipients is to use quadruple immunosuppressive therapy with the induction doses higher than those employed for other organ transplant recipients. For SPK recipients, the allocation of organs should follow the scheme used for that of a kidney alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Graft Rejection↗
PubMed1987

Progress in reconstruction after resection of the head of the pancreas.

Fistulas of the pancreas due to dehiscence of pancreaticojejunostomy after partial pancreaticoduodenectomy caused severe postoperative complications. Whereas various methods with and without anastomosis of the pancreas are recommended to deal with the pancreatic stump, mortality rates of 20 to 75 per cent have been reported. These different results prompted us to start a prospective, nonrandomized study in which three methods of reconstructing the remnant of the pancreas involving anastomosis were compared with pancreaticocutaneous drainage without anastomosis. One hundred and thirty-one patients with partial pancreaticoduodenectomy entered this trial, 54 female and 77 male patients with an average age of 55.9 years. The indications included: 42 instances of chronic pancreatitis, 44 instances of carcinoma of the pancreas and 45, periampullary carcinoma. We performed 33 end to side pancreaticojejunostomy procedures (four fistulas of the pancreas, a mortality rate of 15.0 per cent), 31 end to end anastomoses (three fistulas of the pancreas, a mortality rate of 6.5 per cent) and 48 double loops with anastomoses of the pancreatic and hepatic duct to separate jejunal loops (nine fistulas of the pancreas, a mortality rate of 2 per cent). Nineteen patients were operated upon using external drainage of the pancreatic stump by means of Penrose drains (five fistulas of the pancreas, a mortality rate of zero per cent). To reduce the fatal risks caused by combined fistulas of the pancreas and biliary tract, the use of separate intestinal loops for anastomoses of the pancreas and biliary tract offers the best solution, since no fatal complications of the pancreaticojejunostomy were observed. In contrast, pancreaticocutaneous drainage was performed upon patients with endangered pancreatic anastomoses due to local morphologic conditions, such as tender pancreatic parenchyma or thin pancreatic ducts. The total loss of exocrine function and the high morbidity rate of 37 per cent is justified in spite of the mortality rate of zero per cent. Total pancreaticoduodenectomy, for technical reasons, represents no acceptable alternative in view of higher mortality rates.

Adult↗
PubMed1983

[Clinical significance of pancreas divisum].

Pancreas divisum was demonstrated in 22 of 500 consecutive ERCP (4.4%). Among patients with otherwise normal ERCP, pancreas divisum was found in 12.8%. In contrast, only 1.8% of patients with other pathology in the ERCP exhibited pancreas divisum (p less than 0.001). In relation to the clinical indication, pancreas divisum was found in 13.3% of patients with suspected or proven pancreatitis, in 1.9% of patients with suspicion of biliary tract disease (p less than 0.001), in 1.9% of patients with suspicion of pancreatic cancer (p less than 0,05) and in 4.4% of patients with epigastric pain of undetermined origin (p greater than 0.05). In 14 patients pancreas divisum was the only pathological finding in a thorough clinical and gastrointestinal workup; 6 of the 14 patients had had typical episodes of pancreatitis, in 6 other patients there was clinical and biochemical evidence of pancreatic disease (mainly pain and hyperenzymemia), and the last 2 cases had chronic epigastric pain without biochemical abnormalities. In 2 patients of this series the pancreas divisum was misinterpreted morphologically (sonography, autopsy) as tumor of the head of the pancreas. Based upon our experience and the literature, the following practical conclusions can be drawn: 1. Pancreas divisum may cause typical episodes of acute (relapsing) pancreatitis. 2. In patients with chronic epigastric pain associated with hyperenzymemia but without typical acute pancreatitis, pancreas divisum may be the cause. 3. Morphologically pancreas divisum may mimic a pancreatic tumor (sonography, computer-tomography, autopsy).

Abdomen↗
PubMed1993

Pancreas transplant results in United Network for Organ Sharing (UNOS) United States of America (USA) Registry with a comparison to non-USA data in the International Registry.

As of 1993, more than 5,000 pancreas transplants were reported to the International Pancreas Transplant Registry. More than 3,600 were performed in the USA, including 3,000 since the inception of the UNOS Registry in October, 1987. The BD technique was used for 96% of USA cases but for only 63% of non-USA cases. In the overall analysis of USA BD cadaveric pancreas transplants reported to the Registry by November 1993 (n = 2,464), patient survival and pancreas graft function survival rates at one year were 91% and 72%, respectively, 87% and 67% at 2 years, and 84% and 62% at 3 years. When the USA data for BD cases were analyzed according to the 3 major recipient categories (simultaneous pancreas/kidney transplants [SPK] [n = 2,112]; pancreas after kidney transplants [PAK] [n = 205]; and pancreas transplants alone [PTA] [n = 147]), patient survival rates were no different (91%, 92%, and 91% at one year, respectively), but pancreas graft survival rates were significantly higher in the SPK than in the PAK and PTA categories (76%, 47%, and 48%, at one year, respectively). In the SPK group, kidney graft survival rates at one year were 85%. Although the overall results were not as good for non-USA as for USA pancreas transplants, this was probably because the results with non-BD techniques were not as good as when BD was used, and in Europe more than one-third of the cases used techniques other than BD. The patient, pancreas, and kidney graft survival rates for BD SPK transplants in Europe (n = 522) and other non-USA locations (n = 64) were similar to those in the USA: in Europe 93%, 77%, and 84%, respectively, at one year. The graft survival rates for solitary pancreas transplants, however, were higher in the USA. Outcomes were also compared according to whether induction immunotherapy in USA recipients included ALG/ATG, OKT3, or neither. In the SPK category, there was no difference among the protocols: one-year graft survival rates were 76% with ALG/ATG (n = 1,141), 78% with OKT3 (n = 673), and 71% with neither (n = 249). In the PAK category, the use of OKT3 (n = 37) was associated with lower graft survival rates than when ALG/ATG (n = 133) or neither (n = 34) were given: 26%, 58%, and 53% at one year, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1993

[Changes in the mouse pancreas after reopening the closed pancreatic duct: a qualitative and quantitative histologic study].

To understand histologic regeneration of deteriorated pancreas, pancreatic duct was clipped at 6 weeks of age in mice, the clip was removed 1 week after clipping, and the pancreas was histologically examined 1,2,3,5,7 and 14 days after removing the clip. For quantitative evaluation of the histologic changes, volume of the pancreatic parenchyma and volume densities, numerical densities, and relative total numbers of acinar cells and ductular cells in the pancreas were obtained by a stereological method using serial sections. In addition, the size and mitotic index was estimated for each cellular components. The pancreas was reduced to 18% of the normal after 1 week clipping. Exocrine acinar cells had degenerated and disappeared and the atrophied lobules were occupied by duct-like structures composed of cells like intercalated duct cells. The cells of duct-like structures showed occasional mitotic figures. Dilation of the ducts was noted. The histologic changes in the pancreas after removing the clip were classified with the two different groups (Group A and Group B). Group A pancreas showed regeneration of acinar cells, Group B pancreas showed no evidence of the regeneration. On the 2nd to 3rd days after removing the clip, in Group A pancreas, the lumen of the duct has been shrunken and acinar cells reappeared. Acinar cells were occasionally grouped at the terminal of the ducts. On the 7th day, the duct-like structures had almost disappeared, and exocrine acini were developed to show almost normal appearance of the lobules. The stereometry indicates that, after removing the clip from the duct, the total number of duct cells was decreased, while acinar cells rapidly increased until the 7th day when the increase became gradual, but eventually the recovery of the cell numbers was below the half of the normal range. The findings suggest that 1) duct-like structures in the atrophied pancreas proliferate from ductular cells in the pancreas, 2) reopening of the obstructed pancreatic duct induce regeneration of the acinar cells from the ductular cells, 3) regeneration of acinar cells complete of normal histology but does not recover the normal size of this organ, and 4) the stereological method is appreciated to evaluate correctly a quantitative cell dynamics in the whole organ.

Animals↗
PubMed1988

Early diagnosis and treatment of pancreas allograft rejection.

A major problem in vascularized pancreas transplantation is the lack of reliable methods for the early diagnosis and effective treatment of allograft rejection. Over a 2-year period, 54 rejection episodes occurred in 31 patients (13 isolated pancreas, 18 simultaneous pancreas-kidney recipients) with pancreaticoduodenocystostomy. A total of 253 radionuclide pancreas examinations were performed (mean 8.4 per patient) utilizing 99mtechnetium-DTPA. Computer analysis generated a quantitative measure of blood flow to the allograft caused the technetium index (TI). Rejection episodes were characterized as isolated pancreas (22), combined pancreas-kidney (16), or isolated renal (16) allograft rejection in combined engraftments. The majority of rejection episodes occurred early (within 3 months of transplant, N = 47) and were more responsive than late rejection to anti-rejection therapy (89.4% vs 42.9%, P = 0.01). Mean urinary amylase (UA) levels and TI during normal allograft function were 29,398 U/l and 0.55%, while levels heralding rejection were 6,528 U/l and 0.40%, respectively (P less than 0.05). The treatment of rejection based upon renal dysfunction or combined renal and pancreas dysfunction resulted in significantly higher graft salvage with a lower incidence of hyperglycemia when compared to isolated pancreas allograft rejection. Of the 11 patients who developed hyperglycemia, 8 (72.7%) ultimately lost their pancreas grafts (P less than 0.001). Following therapy, a TI above 0.3% was associated with 97.4% graft survival, while levels below 0.3% resulted in a 70% rate of graft loss (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex Hormones↗
PubMed1997

Interstitial and vascular pancreas rejection in relation to graft survival.

To examine the incidence of interstitial and vascular rejection in pancreas allografts and its impact on graft survival, we studied 36 percutaneous pancreas biopsies and 10 pancreas transplantectomy specimens from 32 patients who had undergone simultaneous pancreas-kidney transplantation. Interstitial rejection (IR) was predominantly found in the biopsies, while vascular rejection (VR) was most prominent in the transplantectomies. Pancreas graft survival was significantly decreased for pancreas graft that had suffered from vascular rejection when compared to those with only interstitial rejection. Potential rejection markers, i.e., serum amylase, glucose, creatinine, and urinary amylase, did not correlate with histological signs of rejection, although increased levels of serum amylase were, in all but one case, associated with rejection. We conclude that a percutaneous pancreas biopsy remains the most reliable method to determine pancreas rejection, and that by distinguishing between IR and VR, a pancreas biopsy may provide important diagnostic as well as prognostic information.

Adolescent↗
PubMed1997

Pancreatitis-associated protein: a putative marker for pancreas graft rejection.

BACKGROUND: Graft rejection is one of the major causes of graft loss after pancreas transplantation. Pancreatitis-associated protein (PAP) is synthesized by the pancreas due to pancreatic inflammation and has shown to be a good serum marker for injury of the pancreas. It may also be potentially useful in the early recognition of rejection and may thus improve pancreas survival. METHODS: We retrospectively evaluated PAP as an early serum marker of pancreas graft rejection in a cross-sectional study in which immunohistochemical analysis of pancreas biopsies was undertaken using antibodies against PAP. PAP concentrations were also measured in sera of blood donors and in patients with renal failure, renal replacement therapy, kidney transplantation alone, and simultaneous pancreas-kidney transplantation. RESULTS: All patients had elevated PAP serum levels compared with blood donors (median PAP: 22 ng/ml, range: 5-75 ng/ml; P<0.0001). Patients on renal replacement therapy had higher values than patients with renal failure (median: 420 ng/ml and 150 ng/ml, respectively). There was a strong inverse correlation between PAP levels and creatinine clearance (P<0.001). PAP values in simultaneous pancreas-kidney transplantation patients with histological rejection were significantly higher than values in those who were clinically stable (median: 925 ng/ml and 322 ng/ml, respectively; P=0.006). Rejection was significantly associated with PAP staining of acinar cell surface. There was also a significant correlation between surface positivity of staining and serum PAP levels (P=0.008). No positive PAP staining was observed in concurrently collected biopsies of renal allografts undergoing rejection. CONCLUSIONS: Serum PAP levels appear to strongly correlate with creatinine clearance measurements. In patients with a pancreas-kidney transplantation, PAP may prove to be a useful biological and histological marker of pancreatic graft rejection.

Acute-Phase Proteins↗