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PubMed1997

Solitary pancreas allografts. The role of percutaneous biopsy and standardized histologic grading of rejection.

OBJECTIVE: To determine the potential impact of ultrasound-guided percutaneous pancreas allograft biopsy and standardized histologic grading on graft and patient survival in a solitary pancreas transplant program. DESIGN: Retrospective case series survey. SETTING: Tertiary care, university teaching hospital. PATIENTS: Thirty-five recipients of solitary pancreas transplants. INTERVENTIONS: Percutaneous pancreas allograft biopsies were performed in solitary pancreas transplant recipients. MAIN OUTCOME MEASURES: Actuarial graft and patient survival, cause of graft loss. RESULTS: Initiation of ultrasound-guided percutaneous pancreas allograft biopsy with standardized histologic grading is associated with a 70% 1-year graft survival and 93% 1-year patient survival in solitary pancreas transplantation. Acute rejection was responsible for only 11% of cases of graft loss. The presence of endotheliitis, vasculitis, or confluent acinar necrosis is associated with decreased pancreas allograft survival, poor response to corticosteroid therapy, and shortened time interval to ultimate graft loss. Clinical criteria for acute rejection such as elevated serum amylase or lipase levels, 50% decrease in urinary amylase levels, unexplained fever, or hyperglycemia are associated with a positive predictive value of only 72%. CONCLUSION: Pancreas allograft biopsy and standardized histologic grading are associated with significantly improved 1-year graft and patient survival in solitary pancreas transplantation.

Actuarial Analysis↗
PubMed1991

Galanin-immunoreactive nerves in the mouse and rat pancreas.

Galanin-containing nerve fibers have previously been observed in the human, dog, and pig pancreas. Whether the mouse and rat pancreas also contain galanin nerve fibers has been a matter of debate. Therefore, we examined the distribution of galanin in the mouse and the rat pancreas. Further, the possible localization of galanin to adrenergic nerves was studied using sequential immunostaining for galanin and tyrosine hydroxylase (TH). In the mouse pancreas, numerous galanin-immunoreactive (GIR) nerve fibers occurred around blood vessels. They were less numerous in the exocrine parenchyma and in association with the islets. In contrast, in the rat pancreas, only a few GIR nerves were found. They were located around blood vessels and scattered in the exocrine parenchyma. Occasionally, GIR nerves were also observed in the islets. There was a dense distribution of TH-immunoreactive fibers in both the mouse and the rat pancreas. Sequential immunostaining revealed co-localization of galanin and TH immunoreactivity in nerve fibers in both the mouse and the rat pancreas. Following chemical sympathectomy using 6-hydroxydopamine (6-OHDA), not all GIR nerves disappeared. In the mouse pancreas a remaining population of galanin nerves was found around blood vessels, and occasionally in the islets. In the rat pancreas, a few GIR nerves were seen also after chemical sympathectomy. We conclude that intrapancreatic GIR nerves also occur in the mouse and the rat. These findings suggest that many of the GIR nerves are adrenergic but that non-adrenergic, possibly intrinsic or sensory GIR nerves exist as well in both the mouse and the rat pancreas.

Adrenergic Fibers↗
PubMed1977

Assessment of endoscopic aspiration cytology and endoscopic retrograde cholangi-pancreatography (ERCP) in patients with cancer of the pancreas. Part I.

This report is concerned with studies on duodenofiberscopic examinations with aspiration cytology endoscopic retrograde cholangio-pancreatography (ERCP) in 44 patients with cancer of the pancreas. Aspiration cytology alone was diagnostic in 91% of cancer of the head of the pancreas, 55% of cancer the body and tail of the pancreas and 100% of cancer of the whole pancreas. ERCP alone was diagnostic in 59% of cancer of the head of the pancreas, 75% of cancer of the body and tail of the pancreas and 100% of cancer of the whole pancreas. By combining these two approach a diagnostic result was obtained in 95% of cancer of the head of the pancreas and 90% of cancer of body and tail of the pancreas. It is concluded that the combined diagnostic approach has enhanced diagnostic accuracy of malignant lesions of the pancreas and that it has not yet led to an improvement resectability and mortality.

Ampulla of Vater↗
PubMed1979

Changes of pancreatic exocrine function after major resection of the pancreas in dogs.

Changes of an exocrine function after major resection of the canine pancreas were observed by pancreozymin-secretin test and the results were compared with an endocrine function examined by glucose tolerance test. The exocrine function of the remnant pancreas revealed characteristic changes according to the resection rate of the pancreas: 1) After removal of 50 to 70 per cent of the entire pancreas, diabetes did not develop and the exocrine function of the remnant pancreas was well maintained. 2) After 70 to 90 per cent pancreatectomy, diabetes developed six weeks or more later and the exocrine function of the remnant pancreas per body weight decreased slightly. The degree of disturbance of the exocrine function in the diabetic dogs was greater than that in the non-diabetic group, but the exocrine function per the remnant pancreas weight increased and it was greater than normal level even in the diabetic dogs. The hypersecretory state of the exocrine pancreas after surgery was verified. 3) After 90 per cent or greater resection of the pancreas, diabetes occurred immediately and disturbance of the exocrine function was remarkable. Hypersecretory state did not appear. 4) Both the endocrine and exocrine functions after major pancreatic resection were found to be related to the resection rate, but there were significant differences in the reserve capacity of the endocrine and exocrine pancreas.

Amylases↗
PubMed1999

Three-dimensional reconstruction of the ventral and dorsal pancreas: a new insight into anatomy and embryonic development.

The recent introduction of limited resections of the ventral pancreas for benign disease and for low-grade malignancies calls for a thorough understanding of its anatomy. The two embryonic anlagen were characterized and distinguished through a comprehensive study of their macroscopic, histologic, and immunohistochemical characteristics in 20 autopsy specimens before reconstruction. Sections were histologically stained with hematoxylin-eosin and Grimelius and immunohistochemically stained with antibodies to insulin, glucagon, somatostatin, and pancreatic polypeptide by the avidin biotin complex method. The ventral and dorsal anlagen of the pancreas were reconstructed from eight autopsy specimens, using the "macroserial" method, after serial sectioning and immunohistochemical staining with anti-pancreatic polypeptide antibodies. Compared with the dorsal pancreas, the ventral pancreas was characterized by the presence of smaller and more closely packed lobuli, irregular rather than uniform islets of Langerhans, and rich immunostaining with anti-pancreatic polypeptide. Construction of the two anlagen showed that the dorsal pancreas consisted of the anterior part of the head of the pancreas, and the body and tail of the pancreas, while the ventral pancreas consisted of the posterior part of the head of the gland and the upper two-thirds (62.5%) or all (37.5%) of the uncinate process. The ventral pancreas was related to the right lateral surface of the superior mesenteric vein extending to the back. However, it did not extend across the front surface of the superior mesenteric vein to the left as previously described. The uncinate process was also located posterior to but not anterior to the superior mesenteric vein. The contributions of the ventral and dorsal anlagen to the anatomy of the pancreas gland as demonstrated in this study differ, in some relevant features, from the classical descriptions in the medical literature. The current anatomical findings add essential knowledge for the pancreatic surgeon who contemplates tissue-preserving resections.

Adolescent↗
PubMed1988

The isolation and characterization of estrogen binding proteins in the pancreas of male and female hamsters.

Specific estradiol binding proteins (EBP) that have been described in the pancreatic tissues of a number of species are thought to be important in maintaining the structural and functional integrity of the pancreas. However, possible sex-related differences in the presence and characteristics of EBP have not been examined. In the present study, we have analyzed the pancreatic tissues of male and female Syrian golden hamsters for the presence of EBP and progesterone binding protein (PBP), and further characterized these sites. Our results indicate the presence of only one class of EBP with a high capacity (greater than 500 fmol/mg protein) and low affinity (Kd greater than 1.0 nM) in the pancreatic cytosol of female hamsters. On the other hand, there appeared to be two distinct classes of EBP in the male pancreas. One class of EBP in the male pancreas had a high binding affinity (Kd = less than 0.05 nM) and low capacity (less than 10 fmol/mg protein); we have arbitrarily called these Type I EBP. The second class of EBP in the male pancreas which resembled EBP in the female pancreas had a high capacity (greater than 100 fmol/mg protein) and a low binding affinity (Kd = greater than 1.0 nM); we have called these Type II EBP. The sucrose-density gradient profile of EBP for male and female hamster pancreas demonstrated the presence of both an 8S binding protein and a 4S binding protein in the male pancreas; the female pancreas had only a 4S binding protein. PBP were not detected in pancreas of either male or female hamsters. We conclude that significant sex-related differences are present in the EBP populations of the hamster pancreas.

Animals↗
PubMed2004

The effect of center volume on pancreas transplant outcomes.

BACKGROUND: Caseload often correlates with improved outcomes for several surgical procedures, including solid organ transplantation. Given the unique nature of pancreas transplantation and large variation in transplant center volumes, this study aims to determine whether center volume affects patient and graft survival after pancreas transplantation. METHODS: Registry data on all forms of whole organ pancreas transplants performed between 1995 and 2000 were obtained from the United Network for Organ Sharing. Patient and graft survival rates were followed until 2002. Center volume then was categorized as: low (< 10/year), medium (10-20/year), high (21-50/year), and very high (< 50/year). Cox proportional hazard regression models were developed to evaluate factors affecting pancreas transplant outcomes. RESULTS: Very-high-volume centers were more likely to do pancreas after kidney transplant, pancreas transplant alone, pancreas with kidney transplant, and repeat transplants, while other centers more frequently performed simultaneous pancreas-kidney transplants (P < .001). Very-high-volume centers were more likely to transplant older recipients and less likely to transplant minority or Medicaid patients. Low-volume centers tended to accept pancreatic allografts from younger donors and had the longest waiting times. In models adjusting for differences in patient population, there were no differences in patient survival. However, low-volume centers had a slightly increased risk of graft loss compared to other centers. Early graft loss was similar among all centers, but medium-volume centers were at increased risk for late graft loss. CONCLUSIONS: Low center volume is not associated with increased mortality after pancreas transplantation. Other factors appear to be more important than center volume in determining pancreas transplant outcomes.

Adult↗
PubMed2004

Cellular localization of endocrine cells in the adult pancreas of the house musk shrew, Suncus murinus: a comparative immunocytochemical study.

The right and left lobes of the pancreas in the house musk shrew, Suncus murinus, were found to be completely separated. A morphologic study of the pancreas in S. murinus in terms of the blood supplies and innervation of the right and left lobes was performed in our previous study. It revealed clearly different blood supply and innervation patterns in the right and left lobes, suggesting that the right lobe of the pancreas corresponded to the ventral pancreas, and the left lobe related to the dorsal pancreas. To test this perspective from the histology, in this study, we investigated the immunolocalization of the cells of Langerhans islets in the pancreas of the animal. The distribution of insulin-, glucagon-, somatostatin-, and pancreatic polypeptide (PP)-secreting cells of the right and left lobes of the pancreas was examined in 10 animals. The glucagon-immunoreactive cells were distributed in both the right and left lobes. The PP-immunoreactive cells were extremely abundant in the right lobe and distributed throughout almost all the islets of Langerhans in the right lobe. By contrast, in the left lobe, immunoreactive PP cells were absent in the islets of Langerhans, and only very few immunoreactive PP cells were scattered in the exocrine parenchyma in part of the specimens. Therefore, these findings support our previous studies, and showed that the right and left lobes of the S. murinus pancreas could be related to an embryological origin from the ventral and dorsal pancreatic primordium, respectively, and that the S. murinus pancreas is suitable as a new experimental model to study the development of the human pancreas.

Animals↗
PubMed1999

Diagnosis of pancreas divisum by endoscopic ultrasonography.

BACKGROUND AND STUDY AIMS: During pancreatobiliary imaging by endoscopic ultrasound (EUS) at the authors' institution, it is customary to attempt to obtain the "stack sign", where the bile duct and the pancreatic duct can be seen to run in parallel through the pancreatic head. We suspected that such a view may not be attainable in patients with pancreas divisum because of the short ventral pancreatic duct. The aim of the study was to investigate whether the presence of pancreas divisum could be suspected on the basis of EUS findings. PATIENTS AND METHODS: The stack sign is obtained by positioning the echo endoscope in the long scope position with the transducer in the duodenal bulb. The balloon is then inflated and advanced snugly into the apex of the bulb. From this position, the bile duct (closest to the transducer) and the pancreatic duct can be seen to run in parallel through the pancreatic head. We attempted to obtain a stack sign during EUS examinations of six patients with pancreas divisum. EUS was done in these patients to look for evidence of chronic pancreatitis and the pancreas divisum was confirmed by endoscopic retrograde pancreatography. An attempt to obtain the stack sign was also made in 30 patients who had EUS for pancreatobiliary indications but did not have pancreas divisum. RESULTS: In only two out of six patients with pancreas divisum (33 %) were we able to obtain a stack sign. This was significantly different from the rate of observation of a stack sign in 83.3 % (25/30) of patients who did not have pancreas divisum (P=0.04). Of the two patients with pancreas divisum in whom a stack sign was seen, the ventral duct was markedly dilated (6.6 mm) in one, and the other patient had an unusually large ventral pancreas. CONCLUSIONS: The absence of a stack sign during pancreatobiliary imaging by EUS may suggest the diagnosis of pancreas divisum.

Congenital Abnormalities↗
PubMed2003

[Pancreas transplantation: a survey on indications, surgical techniques, immunosuppression, complications and outcome].

Since its introduction in 1966, pancreas transplantation has undergone considerable progress. Refinements in surgical technique, better organ preservation solutions, and more potent immunosuppressive therapies have improved patient and graft-survival rates dramatically. Survival rates for patient and pancreas at 1 year approach 95 and 83 %, resp., for simultaneous pancreas and kidney transplantation, and 97 and 78 %, resp., for pancreas alone. US pancreas graft and patient survival rates do not significantly differ from the results of the European centers. However, there is still a hesitant acceptance of combined pancreas-kidney transplantation in Germany. Combined pancreas-kidney transplantation is nowadays the treatment of choice in carefully selected patients with type 1 insulin-dependent diabetes mellitus and end-stage renal failure. Many US centers even advocate combined transplantation in diabetic patients at a pre-uremic stage. Pancreas transplantation significantly improves quality of life and provides excellent long-term glycemic control which halts or even ameliorates secondary diabetic complications such as microangiopathy and neuropathy. In addition, there is increasing evidence that successful pancreas transplantation significantly prolongs patient survival mainly by a reduction of cardiovascular-related mortality. Current 10-year patient survival rate after SPK exceeds 70 %. For diabetics with end-stage renal disease there is no alternative treatment available with comparable live expectancy. However, morbidity and mortality after SPK is still higher than for kidney transplantation alone in the first year. Outcome of isolated pancreas transplantation is also improving but this technique is still restricted to non-uremic patients with severe diabetic complications or with brittle diabetes and severe impairment of quality of life.

Contraindications↗
PubMed1986

Stimulus-secretion coupling in the developing exocrine pancreas: secretory responsiveness to cholecystokinin.

We have studied the onset of secretory responsiveness to cholecystokinin (CCK) during development of the rat exocrine pancreas. Although acinar cells of the fetal pancreas (1 d before birth) are filled with zymogen granules containing the secretory protein, alpha-amylase, the rate of amylase secretion from pancreatic lobules incubated in vitro was not increased in response to CCK. In contrast, the rate of CCK-stimulated amylase discharge from the neonatal pancreas (1 d after birth) was increased four- to eightfold above that of the fetal gland. The postnatal amplification of secretory responsiveness was not associated with an increase in the number or cell surface expression of 125I-CCK binding sites. When 125I-CCK-33 binding proteins were analyzed by affinity crosslinking, two proteins of Mr 210,000 and 100,000-160,000 were labeled specifically in both fetal and neonatal pancreas. To determine if cell surface receptors for CCK in the fetal pancreas are functional and able to generate a rise in the cytosolic [Ca++], we measured 45Ca++ efflux from tracer-loaded lobules. 45Ca++ efflux from both fetal and neonatal pancreas was comparably increased by CCK, indicating CCK-induced Ca++ mobilization and elevated cytosolic [Ca++]. The Ca++ ionophore A23187 also stimulated the rate of 45Ca++ extrusion from pancreas of both ages. Increased amylase secretion occurred concurrently with A23187-stimulated 45Ca++ efflux in neonatal pancreas, but not in the fetal gland. A23187 in combination with dibutyryl cAMP potentiated amylase release from the neonatal gland, but not from fetal pancreas. Similarly, the protein kinase C activator, phorbol dibutyrate, did not increase the rate of secretion from the fetal gland when added alone or in combination with A23187 or CCK. We suggest that CCK-receptor interaction in the fetal pancreas triggers intracellular Ca++ mobilization. However, one or more signal transduction events distal to Ca++ mobilization have not yet matured. The onset of secretory response to CCK that occurs postnatally may depend on amplification of these transduction events.

Animals↗
PubMed1998

Progression of pancreatic intraductal neoplasias to infiltrating adenocarcinoma of the pancreas.

Pancreata with cancer also frequently have intraductal proliferative lesions, suggesting an association between pancreatic cancer and these lesions. We present three cases in which atypical papillary hyperplasia of the pancreas was documented 17 months to 10 years before the development of an infiltrating adenocarcinoma of the pancreas. The first patient was a 70-year-old woman who underwent pancreaticoduodenectomy for adenocarcinoma of the pancreas. Atypical papillary duct hyperplasia extended to the pancreatic neck margin of resection, but the margin was negative for infiltrating carcinoma. Nine years later, an infiltrating adenocarcinoma developed in the remaining pancreas. The second patient was a 58-year-old man who underwent distal pancreatectomy for chronic pancreatitis with pseudocyst. Histologic examination showed chronic pancreatitis and multiple foci of atypical papillary duct hyperplasia. Ten years later, the patient underwent a Whipple procedure for infiltrating adenocarcinoma of the pancreas. The third patient was a 46-year-old woman with recurrent pancreatitis who underwent a Whipple procedure. Histologic examination showed atypical papillary duct hyperplasia and chronic pancreatitis but no infiltrating carcinoma. At the time of surgery, the tail of the pancreas was grossly and radiographically normal. Seventeen months later, a malignant pleural effusion developed, and postmortem examination showed infiltrating adenocarcinoma in the tail of the pancreas. In the cases presented, atypical papillary hyperplasia was documented 17 months, 9 years, and 10 years before the development of infiltrating adenocarcinoma of the pancreas, supporting the concept that there is a progression from intraductal hyperplasia to infiltrating carcinoma of the pancreas, just as there is a progression from adenoma to infiltrating carcinoma in the colorectum. Based on evidence that these intraductal lesions are precursor lesions to infiltrating adenocarcinoma of the pancreas, we suggest that the term "hyperplasia" be replaced by the more specific term "pancreatic intraepithelial neoplasia."

Adenocarcinoma↗
PubMed1998

Surgical complications requiring early relaparotomy after pancreas transplantation: a multivariate risk factor and economic impact analysis of the cyclosporine era.

OBJECTIVES: To study significant surgical complications requiring early (< or = 3 months posttransplant) relaparotomy (relap) after pancreas transplants, and to develop clinically relevant surgical and peritransplant decision-making guidelines for preventing and managing such complications. SUMMARY BACKGROUND DATA: Pancreas grafts are still associated with the highest surgical complication rate of all routinely transplanted solid organs. However, the impact of surgical complications on morbidity, hospital costs, and graft and patient survival rates has not been analyzed in detail to date. METHODS: We retrospectively studied surgical complications requiring relap in 441 consecutive cadaver, bladder-drained pancreas transplants (54% simultaneous pancreas and kidney [SPK]; 22% pancreas after kidney [PAK]; 24% pancreas transplant alone [PTA]; 37% retransplant). Outcome and hospital charges were analyzed separately for recipients with versus without reoperation. RESULTS: The overall relap rate was 32% (SPK, 36%; PAK, 25%; PTA, 16%; p = 0.04). The most common causes were intraabdominal infection and graft pancreatitis (38%), pancreas graft thrombosis (27%), and anastomotic leak (15%). Perioperative relap mortality was 9%; transplant pancreatectomy was necessary in 57% of all recipients with one or more relaps. The pancreas graft was lost in 80% of recipients with versus 41% without relap (p < 0.0001). Patient survival rates were significantly lower (p < 0.05) for recipients with versus without relap. By multivariate analysis, significant risk factors for graft loss included older donor age (SPK, PAK), retransplant (PAK), relap for infection (SPK, PAK), and relap for leak or bleeding (PAK). For death, risk factors included older recipient age (SPK, PAK),retransplant (SPK, PAK), relap for thrombosis (PAK), relap for infection or leak (SPK), and relap for bleeding (PTA). CONCLUSIONS: Posttransplant surgical complications requiring relap were frequent, resulted in a high rate of pancreas (SPK, PAK, PTA) and kidney (SPK, PAK) graft loss, and had a major economic impact (p = 0.0001). Complications were associated with substantial perioperative mortality and decreased patient survival rates. The focus must therefore shift from graft salvage to preservation of the recipient's life once a pancreas graft-related complication requiring relap occurs. Thus, the threshold for pancreatectomy should be low. In this context, acceptance of older donors and recipients must be reconsidered.

Adolescent↗
PubMed1987

Lipid content of human and rat pancreas.

We analyzed the lipid composition of the human pancreas and performed a parallel study on rat pancreas. Some precautions were taken in order to keep the secretory zymogens as inactive precursors in both tissues. The lipid content of the human pancreas corresponded to 5.5% of the tissue wet weight, lower than that found in pancreas of two-month-old Wistar rats (10%). In man, triglycerides and phospholipids were found at comparable levels, respectively, 37 and 30 mg/g of pancreas wet weight, not far from the values of the rat pancreas. In human pancreas, phosphatidylcholines and lysophosphatidylcholines represented about 40% of the total phospholipid fraction, phosphatidylethanolamines and lysophosphatidylethanolamines 21%, and phosphatidylserines and -inositols were found equally represented with 7.5%. The total cholesterol content accounted for about 4.5% of the total lipids; only 30% was esterified. By comparison, in rat, total cholesterol represented 3.3% of lipids and 90% was esterified. The phospholipids in human pancreas contained high amounts of saturated fatty acids (92%) mainly stearic and palmitic, whereas triglycerides contained equal amounts of saturated and unsaturated fatty acids, principally represented by oleic and palmitic acids. In rats the phospholipids contained only 63% saturated fatty acids (palmitic and stearic) and triglycerides contained 61% unsaturated fatty acids (mainly oleic and linoleic). In terms of lipid composition, there is a greater similarity between human and rat pancreas than with other known pancreas, such as the guinea pig and the ox.

Adult↗
PubMed1999

Cholecystokinin A and B receptor mRNA expression in human pancreas.

Little information is available on the expression of cholecystokinin (CCK) receptors in the human pancreas, especially in the developing pancreas. We evaluated expression patterns for the CCK receptors in human pancreas at three different ages: fetus, infant, and adult. Expressions of CCK-A and CCK-B receptor messenger RNA (mRNA) were studied in human midtrimester fetus (14-15 weeks' gestation), infant (50 days old), and adult pancreas by reverse transcription-polymerase chain reaction (RT-PCR) followed by Southern blot analysis. Expression levels of mRNA for both receptors also were evaluated by Northern blot analysis of adult pancreas. Northern blot analysis showed a strong signal for CCK-B receptor mRNA in adult pancreas, but no detectable signal for CCK-A receptor mRNA. However, RT-PCR/Southern blotting showed the presence of CCK-A receptor mRNA in adult pancreas. This was confirmed by sequencing of the complementary DNA (cDNA). RT-PCR/Southern blot analysis also showed CCK-A and CCK-B receptor mRNA expression in fetal and infant pancreas. These results show that the both CCK receptor types are expressed in human pancreas at stages of early gestation, but there is predominant expression of CCK-B receptor in adult pancreas.

Adult↗
PubMed1991

Improvement in islet yield from a cold-preserved pancreas by pancreatic ductal collagenase distention at the time of harvesting.

This study tried to improve the number of viable islets isolated from a pancreas because a sufficient number cannot be obtained when the organ is preserved in the manner used for pancreas transplantation. The mechanism involved in the decrease in islet yield during preservation was studied to try to develop a better method for islet preparation. First, the integrity of the ductal system was compared between fresh and 6-hr simply preserved (in Hanks' balanced salt solution) rat pancreases. The ductal pressure after ductal injection of HBSS reached a plateau earlier and was significantly lower for the preserved pancreases (0.073 +/- 0.026 min, 410 +/- 17 mmHg, n = 5) than for the fresh ones (0.176 +/- 0.086 min, 561 +/- 103 mmHg, n = 7, P less than 0.05). Second, the extent of pancreatic distention was examined following ductal injection of barium gelatin solution. Solution leakage occurred earlier and distention was less in the preserved pancreas. In addition, the gelatin was found in the capillaries within some islets of the preserved pancreas. These results indicated that the preservation led to a rapid loss of integrity of the ductal system before collagenase injection. We therefore tested the efficacy of ductal collagenase injection at the time of harvesting: 15 ml of 1.0 mg/ml collagenase HBSS was intraductally injected and the pancreas was preserved at 4 degrees C for 2, 4, 6, and 24 hr. The isolation procedure was similar to that used for the fresh pancreas. The yield was significantly better than that of the simply preserved pancreas at 4 hr (241 +/- 22, n = 3, vs. 140 +/- 58, n = 3, P less than 0.05) and at 6 hr (171 +/- 58, n = 14, vs. 32 +/- 33, n = 6, P less than 0.01). These isolated islets were spherical-oval and their viability was confirmed by the ability to reverse STZ-induced diabetes in mice. These results indicated that the integrity of the ductal system, which is necessary for distention of the whole pancreas, was lost during preservation. To solve this problem, ductal collagenase injection should be done at the time of pancreas harvesting and then followed by simple preservation. This method is recommended to obtain viable islets from a preserved pancreas.

Animals↗
PubMed1993

Correlation of rejection of the duodenum with rejection of the pancreas in a pig model of pancreaticoduodenal transplantation.

To assess the correlation of rejection in the duodenum and the pancreas, we examined pancreatic and duodenal tissue from pancreaticoduodenal transplants in 32 outbred Yorkshire Landrace pigs. After streptozotocin-induced hyperglycemia, they were transplanted and treated with prednisone, AZA, and CsA. Immunosuppression was reduced by 50% weekly and discontinued at 3 weeks. The tissues were harvested at necropsy at various time points. Each organ was graded for interstitial rejection and vascular rejection separately as no, mild, moderate, and severe. All but 1 animal rejected their organs. Complete concordance of rejection between duodenum and pancreas considering both interstitial and vascular findings was found in 15/32 (47%) animals. In 11/17 (65%) of the remaining allografts, the pancreas had a higher rejection grade (3 interstitial, 5 vascular, 3 both) and in 6/17 (35%) the duodenum had higher rejection grades (2 interstitial, 4 vascular). Considering interstitial and vascular rejection separately, 23/32 (72%) and 20/32 (63%) showed concordance, respectively. Most cases (7/9, 78%) of discordant interstitial rejection showed higher interstitial rejection grades in the pancreas. Five cases (4 pancreas, 1 duodenum) showed interstitial discordance of 2 grades or more. Discordant cases with higher vascular rejection were 7 pancreas (58%) and 5 duodenum. Five cases (3 pancreas, 2 duodenum) showed vascular discordance of 2 grades or more. Interstitial rejection was seen alone (11 cases) and with vascular rejection (20 cases), but vascular rejection was never seen alone. We made the following conclusions. (1) Concordance of duodenal and pancreas rejection occurs in 47% of cases. (2) Discordant cases usually show higher grades of rejection in the pancreas (65%), but the opposite can also occur. (3) Therefore, if duodenal biopsies are positive, they are likely to be representative of pancreatic pathology, but when negative, they do not rule out rejection of the pancreas. (4) Interstitial rejection appears to precede vascular rejection, suggesting that factors released during interstitial rejection play a role in endothelial cell activation and vascular rejection.

Animals↗
PubMed2000

Results of pancreas transplantation after steroid withdrawal under tacrolimus immunosuppression.

PURPOSE: The results of steroid withdrawal in pancreas transplant recipients under tacrolimus immunosuppression were analyzed. METHODS: From July 4, 1994 until April 30, 1998, 147 pancreas transplantations were performed in 141 patients, including 126 simultaneous pancreas-kidney transplantations, 13 pancreas after kidney transplantation, and 8 pancreas transplantations alone. Baseline immunosuppression consisted of tacrolimus and steroids without antilymphocyte induction. Twenty-three patients were excluded from analysis because of early graft loss in 17 cases, retransplantation in 5 cases, and simultaneous pancreas-kidney transplantation after heart transplantation in 1 patient. RESULTS: With a mean follow-up of 2.8+/-1.1 years (range 1.0 to 4.8 years), complete steroid withdrawal was achieved in 58 (47%) patients with a mean time to steroid withdrawal of 15.2+/-8 months (range 4 to 40 months after transplantation). Of the entire cohort of 141 patients, overall 1-, 2-, and 4-year patient survival rates were 98%, 95.5%, and 86%, respectively. Overall 1-, 2-, and 4-year graft survival rates were 83%, 80%, and 71% (pancreas) and 95%, 91%, and 84% (kidney), respectively. Of the 124 patients analyzed for steroid withdrawal, 1-, 2-, and 4-year patient survival rates were 98%, 97%, and 92%, respectively. Overall 1-, 2-, and 4-year graft survival rates were 98%, 91.5%, 83% (pancreas) and 97%, 95%, and 91% (kidney). Patient, pancreas, and kidney survival rates at 1 year were 100%, 100%, and 98% (off steroids) versus 97%, 91%, and 96% (on steroids, all NS) and at 4 years were 100%, 94%, and 95% (off steroids) versus 78%, 68%, and 85% (on steroids, P = 0.01, 0.002, and NS, respectively). The cumulative risk of rejection at the time of follow-up was 76% for patients on steroids versus 74% for patients off steroids (P = NS). Seven patients originally tapered off steroids were treated for subsequent rejection episodes, which were all steroid sensitive, and two of these seven patients are currently off steroids. Thirteen patients received antilymphocyte therapy for steroid-resistant rejection, five of whom are now off steroids. Tacrolimus trough levels were 9.3+/-2.4 ng/ml (off steroids) and 9.7+/-4.3 (on steroids, P = NS). Mean fasting glucose levels were 98+/-34 mg/dl (off steroids) and 110+/-41 mg/dl (on steroids, P = NS). Mean glycosylated hemoglobin levels were 5.2+/-0.9% (off steroids) and 6.2+/-2.1% (on steroids, P = 0.02), and mean serum creatinine levels were 1.4+/-0.8 mg/dl (off steroids) and 1.7+/-1.0 mg/dl (on steroids, P = 0.02). CONCLUSION: These data show for the first time that steroid withdrawal can be safely accomplished in pancreas transplant recipients maintained on tacrolimus-based immunosuppression. Steroid withdrawal is associated with excellent patient and graft survival with no increase in the cumulative risk of rejection.

Graft Rejection↗