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PubMed1995

Constitutive (pro)insulin release from pancreas of transgenic mice expressing monomeric insulin.

To evaluate the role of protein aggregation and calcium in the sorting of insulin for regulated vs. constitutive release from the intact pancreas, we targeted the expression of a monomeric mutant form of human (pro)insulin (B9/B27) to the pancreatic beta-cells of transgenic mice. This mutant insulin does not form dimers or hexamers, but can aggregate at high concentration in the presence of calcium. A homozygous line (171) was produced that expressed 55% of the total (pro)insulin message in their beta-cells as the mutant form and had normal pancreatic total (pro)insulin content [measured as immunoreactive insulin (IRI)]. Fasting glucose levels in these transgenics and in homozygous control mice expressing native human (pro)insulin were normal, although levels were abnormally elevated during ip glucose tolerance testing. In the presence of extracellular calcium, regulated IRI release from the isolated perfused pancreas of the transgenic mice was undetectable in the absence of secretagogues and responded with normal phasic kinetics when stimulated with increasing steps of glucose, with glucose plus isobutylmethylxanthine, or with arginine. Without extracellular calcium (0 calcium plus EGTA), normal pancreas did not release IRI in either the presence or absence of secretagogues. In contrast, without calcium or secretagogues, transgenic pancreas spontaneously and constitutively released IRI at high levels equivalent to those elicited by glucose (22 mM) plus calcium from normal pancreas. This release was partially inhibited by glucose or arginine. Constitutive secretion was acutely sensitive to calcium; inhibition occurred within minutes after the addition of calcium and quickly returned to its characteristic level (with overshoot) when calcium was subsequently removed. Somatostatin, at a concentration that caused 50% inhibition of normal glucose-stimulated secretion, did not affect constitutive release. Control pancreas from the transgenic mice, expressing native human (pro)insulin, responded normally to secretagogues and did not constitutively release hormone in the absence of calcium. It is concluded that expression of monomeric human insulin in pancreatic beta-cells from transgenic mice did not interfere with normal phenotypic insulin secretion, indicating that the functional secretory apparatus was not impaired. Constitutive secretion of IRI from the intact pancreas requires both the expression of a monomeric form of insulin and the absence of extracellular calcium, two conditions that reduce aggregation. These results are consistent with the hypothesis that protein aggregation favors sorting to the regulated pathway, whereas suppressed aggregation causes sorting for constitutive release.

Animals↗
PubMed1982

[Pathophysiology in diabetes after major resection of the pancreas, with special reference to insulin metabolism and glucagon secretion (author's transl)].

Recently, major resection of the pancreas has been carrier out not only to treat pancreatic carcinoma but also for benign pancreatic diseases. Dragstedt reported that the amount of insulin required to control glycosuria after partial pancreatectomy is much greater than that needed after total pancreatectomy. Although it is thought that diabetes after partial pancreatectomy is considerably different from that after total pancreatectomy, these pathophysiological changes have not been investigated in detail. In the present experiment, changes in carbohydrate and insulin metabolism and glucagon secretion were studied in dogs in order to elucidate the pathophysiology in diabetes after major resection of the pancreas. Immediately after resection of 90% or more of the entire pancreas, diabetes occurred with absolute insulin deficiency, being accompanied by decreased function of the anti-insulin system with poor secretion of glucagon and delayed recovery of blood sugar after the insulin load. Moreover, the half-life of insulin in this group was much longer than that in normal dogs and close to that after total pancreatectomy. These results could explain that the dosage of insulin required to control blood sugar after resection of 90% or more of the entire pancreas was close to that after total pancreatectomy. Six weeks or more after resection of 70 to 90% of the entire pancreas, so-called Sandmeyer's diabetes gradually as a consequence of a decrease in insulin secretion and an increase in glucagon secretion from the remnant pancreas. After the insulin load, glucagon secretion markedly increased and recovery of blood sugar from the insulin hypoglycemia was good, showing hyperfunction of the anti-insulin system. Moreover, the half-life of insulin gradually lengthened but was still shorter than that after total pancreatectomy. These results could well explain the fact that the insulin dosage required to control blood sugar in Sandmeyer's diabetes was 3 to 4 times more than that needed after total pancreatectomy. After resection of less than 70% of the entire pancreas, diabetes did not occur throughout a period of post-operative observation of up to 66 weeks. After the insulin load, glucagon secretion and recovery rate of blood sugar from the insulin hypoglycemia were maintained well, showing normal function of the anti-insulin system, and the half-life of insulin was also within the normal range.

Animals↗
PubMed1997

Solitary pancreas transplantation. Experience with 62 consecutive cases.

OBJECTIVE: To determine the safety and efficacy of solitary pancreas transplantation in the treatment of IDDM. RESEARCH DESIGN AND METHODS: A single-center retrospective case series of 62 consecutive solitary pancreas transplants (20 sequential pancreas after kidney, 42 pancreas transplants alone) performed in 57 adult IDDM patients was studied. Indications for solitary pancreas transplantation were 1) the presence of two or more overt diabetic complications and/or 2) glucose hyperlability with hypoglycemic unawareness and impaired quality of life. The recipient group consisted of 31 men and 26 women with a mean age of 38 years (range 25-62) and a mean duration of diabetes of 26 years (range 14-52). Mean pretransplant glycohemoglobin level was 9.9 +/- 2.6%. Organ acceptance was restricted to ideal donors and man-dated a minimum of a two-antigen match (mean human leukocyte antigen ABDR match 2.7). The mean cold ischemia time was 16.6 h. Whole-organ pancreas transplantation was performed with bladder drainage by the duodenal segment technique. All patients were managed with either triple or quadruple immunosuppression. Monitoring included prospective urine cytology as well as cystoscopic transduodenal needle biopsies. RESULTS: The mean length of initial hospital stay was 18 days, and mean hospital charges were $106,341. The incidences of rejection, infection, and surgical complications were 70, 55, and 47%, respectively. Overall patient and graft survival rates were 86 and 52%, respectively, with a mean follow-up of 28 months. All patients with functioning grafts had excellent metabolic control (mean glycohemoglobin level 5.1%) and achieved good rehabilitation. CONCLUSIONS: Despite morbidity, solitary pancreas transplantation can be performed with improving success, can enhance quality of life, and can offer an opportunity to arrest secondary diabetic complications.

Adult↗
PubMedDate not supplied

Benign pancreatic tumor treated with duodenum-preserving resection of the head of the pancreas. Case report.

Cystic neoplasms of the pancreas constitute about 9% of all cystic lesions of the pancreas and less than 1% of all pancreatic neoplasms. Authors report the case of a 70 year-old woman with microcystic cystadenoma. Computed tomography (CT) scan of the abdomen diagnosed a 5 cm multilocular septated cyst, with calcifications in the context, localized in the head-uncinate process of the pancreas. The mass was well separated by a sharp cleavage plane with portal vein and superior mesenteric vessels. An endoscopic retrograde cholangiopancreatography (ERCP) showed cephalic symmetrical stenosis (diameter: 3 mm) of the main pancreatic duct (MPD), mildly dilated in the remaining tract (diameter: 6 mm). An intra-operative biopsy of the cystic wall had been performed. Therefore, it was decided to proceed with a duodenum-preserving resection of the head of the pancreas (DPPHR), including stenosis tract of the MPD in the surgical specimen. The reconstructive procedure consisted, by i.v. jejunal loop transposition, of a side-to-side pancreatico-jejunostomy, including in the anastomosis both corpocaudal stump and the resection cavity of the pancreatic head, and an end-to-side Roux-en-Y jejuno-jejunostomy. With respect to long-lasting pain relief and preservation of the endocrine and exocrine functions of the pancreas, duodenum-preserving resection of the head of the pancreas is a highly effective surgical procedure with low early and late morbidity and mortality due to limited surgical resections. This technique, introduced into surgical practice in 1972 by Beger, is indicated in patients with chronic pancreatitis with an inflammatory mass in the head of the pancreas. The authors conclude that this procedure can also be performed in cases of pancreatic benign tumors, such as microcystic cystadenoma. Advantages of this technique make DPPHR an attractive alternative to pylorus-preserving pancreatico-duodenectomy (PPPD).

Aged↗
PubMed1999

P16INK4a expression adenovirus vector to suppress pancreas cancer cell proliferation.

The prognoses of pancreatic cancer patients have been miserable even after radical surgery, and adjuvant therapy is necessary to improve the surgical results. p16(INK4a) (p16) is tight-binding and inhibitory protein for cyclin-dependent kinase 4 to induce G1 arrest of the cell cycle. p16 gene deletion is frequently identified in human pancreas cancer. The impaired gene function of p16 might be a major factor of the uncontrolled proliferation and malignancy of pancreas cancer cells. In this study, we investigated the effect of adenovirus p16 expression vector for pancreas cancer cell proliferation to clarify whether the vector might be a promising mode to assist the surgical therapy for pancreas cancer. We constructed the adenovirus p16 expression vector AdexCACSp16 by inserting p16 cDNA to a cassette cosmid containing a nearly full-length adenovirus type 5 genome with E1 and E3 deletions. Thereafter, we assessed the activity of AdexCACSp16 to induce p16 gene mRNA expression in pancreas cancer cell line MIAPaCa-2 and to control cell proliferation. AdexCACSp16 induced a high level of p16 gene mRNA expression in MIAPaCa-2 cells with 1 h contact to the cells. The cell proliferation was significantly suppressed by AdexCACSp16 compared with the control adenovirus group. These data indicate that AdexCACSp16 has the potential to induce p16 gene expression and control pancreas cancer cell proliferation and that the adenovirus p16 expression vector AdexCACSp16 might be a possible method of gene therapy to improve the surgical therapeutic results for pancreas cancer.

Adenoviruses, Human↗
PubMed1983

[Gastric secretion after major resection of the pancreas, with special reference to gut hormones and gastric acid secretion in Sandmeyer's diabetes].

The influences of major pancreas resection upon gastric acid secretion and gut hormones were studied in dogs with Heidenhain pouches. Immediately after resection of 90% or more of the entire pancreas, diabetes occurred with an abrupt decrease in insulin and glucagon secretion, and a marked increase in gastric acid output, though gastrin secretion decreased and secretin secretion increased, as after total pancreatectomy. Six weeks or more after resection of 70 to 90% of the entire pancreas, so-called Sandmeyer's diabetes occurred as a consequence of a decrease in insulin secretion and an increase in glucagon secretion from the remnant pancreas. Gastric acid output decreased markedly, and gastrin secretion also decreased. After resection of less than 70% of the entire pancreas, diabetes did not occur during 66 weeks of the longest observation period after surgery. Gastric acid output, secretion of gastrin and secretin did not change after surgery. These results suggest that gastric hypersecretion occurs after total pancreatectomy and resection of 90% or more of the entire pancreas, and it is related to pancreatic exocrine insufficiency and that gastric hyposecretion occurs after resection of 70 to 90% of the entire pancreas, and it may be related to hypersecretion of glucagon and somatostatin.

Animals↗
PubMed1997

Laparoscopic distal resection of the pancreas with the preservation of the spleen.

UNLABELLED: Management of the pancreatic diseases is still a challenge to the laparoscopic technique. Some experience has been gained in the laparoscopic exploration of the pancreas and staging in cancer. Anatomically the accessibility of the distal pancreas provides the laparoscopic approach technically feasible. PATIENT AND METHOD: A case of insuloma in the tail of the pancreas is presented, where distal pancreatic resection was performed laparoscopically with the preservation of the spleen. In a 55 years old female patient with typical clinical symptoms of hyperinsulinism CT identified a 3 cm large solid tumor in the tail of the pancreas. Complete mobilization of the distal pancreas was enhanced by the use of an ultrasonic dissector (UltraCision). The pancreas is detached from the splenic hilum after dividing the spleen vessels. The pancreas is transected proximally by laparoscopic linear stapler. Preservation of the short gastric vessels provides the necessary blood supply of the spleen following division of the splenic artery and vein. Thus removal of the spleen is not a necessary step in this procedure. The operation was carried out within 4.5 hours. Postoperative course was uneventful, the patient left the hospital on the 5th postoperative day. Advantages of the procedure were the earlier mobilization and shorter recovery time, less postoperative pain. The procedure can be safely performed with a good experience in both pancreatic and laparoscopic surgery.

Early Ambulation↗
PubMed1998

The risk of subsequent primary carcinoma of the pancreas in patients with cutaneous malignant melanoma.

BACKGROUND: Carcinoma of the pancreas is the fifth leading cancer in the U.S. and has the poorest survival rate of the major malignancies. Recent studies have reported an increased risk of carcinoma of the pancreas in malignant melanoma-prone kindreds and have suggested a link between malignant melanoma and pancreas carcinoma and mutations in the p16INK4 gene. This study evaluates the risk of carcinoma of the pancreas in a population-based cohort of patients with malignant melanoma. METHODS: The malignant melanoma patients were identified from the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute. The cohort was followed within the SEER system to ascertain the occurrence of subsequent microscopically confirmed primary carcinoma of the pancreas from January 1973 through December 1993. The time of follow-up was expressed as person-years of observation. Standardized incidence ratios (SIR) and 95% confidence intervals (95% CI) were calculated. RESULTS: There were 43,781 malignant melanoma patients providing 263,528 person-years of follow-up. A nearly 2-fold increased risk of subsequent carcinoma of the pancreas in patients diagnosed with malignant melanoma before age 50 years was observed (SIR = 1.76; 95% CI = 0.80-3.34) and the greatest estimated risk occurred in young white females (SIR = 2.27; 95% CI = 0.73-5.30). CONCLUSIONS: These results provide some evidence in support of observations in recent studies that not only a family history of malignant melanoma but also malignant melanoma diagnosed at an early age may be associated with the subsequent development of carcinoma of the pancreas. Further research with larger numbers of melanoma patients is necessary to explore these potential associations.

Adolescent↗
PubMedDate not supplied

An introduction to mucin-producing tumors of the pancreas: why they deserve more attention.

BACKGROUND/AIMS: Mucin-producing tumors of the pancreas are clinically characterized by dilatation of the major pancreatic duct due to pooled mucin, and by dilatation of the orifice of the duodenal papilla. The concept of mucin-producing tumors of the pancreas was proposed in 1982, but has undergone revision since then. METHODOLOGY: The present paper reviews the history, classification, and description of mucin-producing tumors of the pancreas. Problems relating to this type of tumor are also discussed. RESULTS: The clinical concept of mucin-producing tumors of the pancreas has affected studies of the pancreatic diseases in many areas. First, when recognition of pancreatic cancer with a relatively good prognosis commenced, this concept led to awareness of the necessity for a detailed examination of the pancreatic duct epitheliums in cases of suspected pancreatic carcinoma. Second, the concept made it easier to diagnose carcinoma in situ. Third, new classifications of cystic lesions of the pancreas were initiated. Fourth, a molecular biological view of the onset of pancreatic cancer was developed. Pathologically, this type of tumor is characterized by papillary growth of the epitheliums within the pancreatic duct, and it has been regarded as having a good prognosis. The term mucin-producing tumors of the pancreas now includes: intraductal papillary tumors which are non-invasive carcinomas or carcinoma in situ; duct-ectatic tumors, or mucinous cystic tumors; and, invasive carcinomas, derived from the former types. CONCLUSIONS: The definition of "mucin-producing tumor of the pancreas" has been undergoing revision. In the past, it has referred to pancreatic tumors with a good prognosis. It is now time to consider a more detailed classification.

Adenocarcinoma, Mucinous↗
PubMed1983

History of the pancreas.

The pancreas was generally ignored in antiquity, both as an organ and as a seat of disease. The first description of the pancreas is attributed to Herophilus. It was in the 17th century that the main duct of the organ was described and its significance demonstrated. At that time, Brunner thought that the pancreas was not essential to digestion, and he failed to associate the pancreas with diabetes. Claude Bernard discovered the function of the pancreas in digestion. In 1922, Banting and Best obtained isletin and demonstrated the capacity of the substance to cause a dog to recover from diabetic coma. In 1889, Reginald Fitz firmly established pancreatitis as a disease entity. In 1927, the first case of hyperinsulinism due to a tumor of the islet cells was reported. Twenty-eight years later, Zollinger and Ellison described two patients with unusually severe peptic ulcer disease, both of whom had noninsulin-secreting tumors of the pancreatic islets. Subsequently, gastrin was isolated as the hormone responsible for this syndrome. In March 1940, Dr. O. Whipple performed the first recorded one-stage pancreaticoduodenectomy. Much progress has been made since then and today transplantation of isolated islets and portions of whole pancreas is a reality.

Animals↗
PubMed1990

Prostaglandin E2 and thromboxane B2 levels in rats subjected to pancreas transplantation.

This work undertakes the study of changes in urinary, plasmatic and tissue levels of Thromboxane B2 (TXB2) as well as in tissue Prostaglandin E2 (PGE2) after pancreas transplantation and the effect of superoxide dismutase (SOD) on these changes. For this purpose, streptozotocine induced diabetic rats were subjected to pancreas transplantation. Experimental groups were classified as follows: Group I: Control; Group II: Animals subjected to 15 min of pancreas arterial flow occlusion followed by reperfusion; Group III: Syngenic pancreas transplantation after 12 hours of organ preservation; Group IV: Same as III, but with additional SOD (13 mg/kg) pretreatment. The results indicate that significant increases of PGE2 and TXB2 levels occur as a consequence of the surgical removal, preservation and implantation of the organ. For TXB2 these increases, immediate in plasma and tissue, are not detected in urine until 24 hours after transplantation of the pancreas. The release of TXB2 and PGE2 was effectively prevented in the SOD treated group supporting the role of oxygen free radicals and lipid peroxidation in the processes of ischemia-reperfusion associated to transplantation of the pancreas.

Animals↗
PubMed2003

Improved ultrasound examination of pancreas grafts in type 1 (insulin-dependent) diabetic patients using tissue harmonic imaging.

BACKGROUND: Combined kidney/pancreas transplantation is an established therapy for type 1 diabetic patients with end-stage renal disease. Ultrasound examinations are valuable noninvasive methods for postoperative monitoring of transplant recipients. Kidney grafts are easily to detect, whereas pancreas grafts are surrounded or covered by small bowel loops, which makes the examination much more difficult. PATIENTS AND METHODS: Thirty-three simultaneous pancreas and kidney recipients (SPK) were examined by conventional sonography at 3.4 MHz and THI sonography (pulse inversion, 2.3 MHz) by an investigator experienced in abdominal ultrasound. The images were graded by two "blinded readers" using a scale (1-best image quality, 2-second best, 3-worst) with regard to tissue penetration and detail characterization of the pancreas grafts. The graders were unaware of the sonographic technique, respectively. Statistical evaluation was performed by the Mann-Whitney U test. RESULTS: In 25 cases (78%) pancreas grafts were detected by conventional sonography. The detection rate was higher using THI sonography, namely 29 cases (91%). Grading for tissue penetration revealed a mean value of 2.05 +/- 0.5 for conventional and 1.94 +/- 0.5 for THI sonography (P =.27). Detail characterization of the pancreas grafts was determined to show a mean value of 2.50 +/- 0.5 for conventional sonography and a significantly better mean value of 1.78 +/- 0.6 for THI sonography (P <.0001). CONCLUSION: THI sonography improves the detection and the judgment of tissue characteristics of pancreas grafts. Penetration of ultrasound waves is not relevantly decreased by this new technique.

Adult↗
PubMed2003

Culture-negative peritoneal dialysis peritonitis associated with pancreaticoduodenocystotomy leak of a pancreas transplant.

BACKGROUND: Peritoneal dialysis (PD) peritonitis is usually caused by infection and less commonly by a sterile inflammatory reaction. METHODS: The authors report the case of a kidney-pancreas transplant recipient who was receiving PD after kidney transplant rejection 5 years after transplantation. The patient had a viable pancreas transplant. He had abdominal pain associated with cloudy PD effluent. The PD leukocyte count was elevated with a predominance of monocytic leukocytes. RESULTS: Blood, urine, and PD effluent cultures were negative. An ultrasound scan of the transplanted kidney and a computerized tomography (CT) scan of the abdomen and pelvis did not identify the cause of the peritonitis. Foley catheter decompression of the bladder resulted in improvement of the abdominal pain and PD effluent leukocytosis. Twenty-five days later, the patient again experienced abdominal pain and cloudy PD effluent. Cultures of blood and PD effluent were again negative. CT scanning and cystoscopy of the transplanted pancreas identified a leak at the pancreaticoduodenocystotomy anastamosis. Urinary bladder decompression was followed by surgical exploration that identified an erosion of the distal transplanted duodenum, necessitating enteric diversion of the transplanted pancreas's exocrine secretions. The patient underwent conversion to hemodialysis, and the pancreas transplant continued to function well. He has subsequently received a living related kidney transplant. CONCLUSION: This is the first reported case of noninfectious PD peritonitis caused by pancreaticoduodenocystotomy leak in a patient with a functional pancreas transplant.

Abdominal Pain↗
PubMed1999

Vascularized pancreas allotransplantation--clinical indications and outcome.

AIMS: This review examines the status of vascularized pancreas transplantation as a treatment for Type 1 diabetes mellitus (DM). METHODS: The world literature, with a particular emphasis on data from the International Pancreas Transplant Registry (IPTR), is reviewed and interpreted particularly for clinical indications and outcome. RESULTS: Over 9000 cases of vascularized pancreas transplant (VPT) have been registered, with insulin dependence approaching 82% at 1 year with 94% patient survival. The majority of transplants are simultaneous pancreas and kidney (SPK) transplants, with far fewer pancreas after kidney (PAK) or pancreas transplants alone (PTA). The success rates differ between the procedures but are generally improving as technical advances, improvements in immunosupression and greater experience are gained. The most obvious advantage is an improved quality of life (QoL) but there are risks associated with the procedure and with the immunosuppression. There is some evidence coming to light of a very slow beneficial effect on microvascular complications. CONCLUSIONS: VPT is an attractive option to offer Type 1 DM patients who need or already have a renal allograft. Patients have to decide between the increased surgical risk and the risks of long-term immunosuppression and the benefits of improved QoL. In the absense of end-stage renal failure (ESRF) there is no justification for PTA, except where the diabetes itself poses a greater risk to life than the transplantation procedure.

Diabetes Mellitus, Type 1↗
PubMed1984

One hundred pancreas transplants at a single institution.

Clinical pancreas transplantation at the University of Minnesota began in 1966. An initial series of 14 whole pancreas grafts was reported in part to the American Surgical Association in 1970. Only one patient survived for more than 1 year with a functioning graft. Twenty attempts at islet allotransplantation in the mid-1970s were unsuccessful. In 1978 we resumed performing pancreas transplants by the segmental technique, allowing the use of related donors. The current series (July 25, 1978 to December 20, 1983) includes 86 pancreas transplants (51 cadaver, 35 related) in 75 patients (41 with and 34 without previous kidney grafts). Variations in management of the pancreatic duct include three ligated, 15 duct-open, 39 duct-injected, and 29 pancreaticojejunostomies. The latter technique is currently preferred. Currently (April 1984) 61 patients are alive (81%), 24 have functioning grafts (32%), and 21 are insulin-independent (28%), three with open-duct grafts for 4.4 to 5.7 years, seven with silicone-injected grafts from 10 to 39 months, and 14 with pancreaticojejunostomies for 3 to 31 months; 15 of the grafts have functioned for greater than 1 year. Twenty-two of the grafts (25%) failed for technical reasons (thrombosis, infection, or ascites); 35 grafts functioned for 1 to 13 months before totally failing from either rejection, fibrosis, or recurrent disease; five patients died with functioning grafts. The graft survival rate has been higher for pancreases from related (15/35, 43% functioning) than from cadaver (9/51, 18% functioning) donors. The success rate has increased, e.g., 11/22 recipients of pancreas transplants in 1983 currently have functioning grafts (50%). Metabolic studies show most patients with functioning grafts to be euglycemic; however, three of 24 have chronic hyperglycemia unless supplemented with insulin, but they are no longer ketosis-prone. Glucose tolerance test results are normal or nearly normal in 12 and abnormal in 12 of the recipients with currently functioning grafts. Regression of diabetic nephropathy has been documented in two long-term recipients. Pancreas transplantation is currently applicable as treatment for selected diabetics who have demonstrated their propensity to develop serious secondary complications.

Adult↗
PubMed1997

Duct epithelial cells cultured from human pancreas processed for transplantation retain differentiated ductal characteristics.

A procedure is described for the isolation and growth in vitro of epithelial cells from the duct network of human pancreas, referred to as DEC. A significant advantage of our procedure over previously published procedures is that it enables the isolation of DEC from small pieces of pancreas tissue (< 5 g) and, also, from the digest remaining after the isolation of islet cells from human pancreas, material that would normally be discarded. These were the only reliable sources for pancreas tissue available to us. This procedure shows that some of the techniques that have been successfully used for the isolation of rodent DEC are also valuable in the isolation of human DEC. In particular, the use of cholera toxin to prevent fibroblast growth and contamination obviates the need for the time-consuming procedure of physically removing fibroblasts or the use of expensive fibroblast-specific monoclonal antibodies. The use of sieving to separate the digest immediately achieves a partial purification, which, coupled with that of allowing duct cysts to form, adds to the purity of the final preparation. The ductal system of the intact pancreas tissue and the DEC derived from it expressed cytokeratins 7, 8/18, and 19 and markers for the presence of MUC1, CFTR, and carbonic anhydrase II, which are specific for ductal epithelial cells or for pancreatic ductal functions. This study showed that it is possible to obtain selectively viable DEC from small ducts in otherwise waste pieces of human pancreas. It showed that these cells retained all of the epithelial characteristics that were examined and, in combination with data from an earlier study, showed that the cultured DEC retain the metabolic functions of duct epithelial cells in vivo.

Antibodies, Monoclonal↗
PubMed1991

Percutaneous biopsy of bladder-drained pancreas transplants.

Percutaneous biopsy is a valuable investigation in the management of allograft rejection for all solid organs. Pancreas transplants have not been biopsed percutaneously, though open and percystoscopic biopsies have proved useful. We have compared percutaneous needle core biopsy with fine-needle aspiration cytology for the diagnosis of rejection in 18 patients receiving combined kidney and pancreas transplants and in one who was transplanted with the pancreas alone. Percutaneous needle core biopsy was successful in 37 of 40 attempts (93%), while fine-needle aspiration yielded diagnostic material on 33 of 47 attempts (70%). Transient hyperamylasemia occurred in 29%, returning to baseline in three days. One patient twice developed transient macroscopic hematuria. There was agreement between needle core biopsy and fine-needle aspiration on the diagnosis of rejection on six occasions and for the absence of rejection on 16. There was an 8% false-positive rate for fine-needle aspiration. In 13 instances of histologically proved renal rejection, concurrent pancreas biopsy revealed rejection in 69%. Pancreas rejection was not, however, seen in the absence of renal rejection. In this pilot study, percutaneous biopsy of the bladder-drained pancreas allograft was shown to be a practicable and valuable investigation without major complications.

Adult↗
PubMed1992

The mechanism of action of the two-layer (Euro-Collins' solution/perfluorochemical) cold-storage method in canine pancreas preservation--the effect of 2,4 dinitrophenol on graft viability and adenosine triphosphate tissue concentration.

Tissue concentrations of adenosine triphosphate have been previously associated with successful pancreas preservation using the two-layer cold storage method in a canine autotransplantation model. To clarify the role of ATP vs. oxygenation per se, we used 2,4 dinitrophenol, an uncoupler of mitochondrial oxidative phosphorylation. DNP caused no toxicity in pancreas grafts preserved for 24 hr in Euro-Collins' solution or 48 hr in University of Wisconsin solution. Tissue concentration of ATP and viability of pancreas grafts, defined as maintenance of normoglycemia for 5 days following transplantation, were compared among six groups after a preservation interval of 24 or 48 hr. After 24 hr all grafts were viable, whether preserved using simple cold storage in EC (group 1a), two-layer (EC/perfluorochemical [PFC]) method (group 2a), or two-layer (EC+DNP/PFC) method (group 3a); respective graft survival was 4/4 (100%), 5/5 (100%), and 4/5 (80%); one of five dogs in group 3a died of a cause unrelated to the pancreas. ATP levels were higher in group 2a compared with group 1a (7.47 +/- 0.47 vs. 1.41 +/- 0.53 mumol/g dry weight, P less than 0.01) and lower in group 3a compared with group 2a (1.25 +/- 0.37 vs. 7.47 +/- 0.47, P less than 0.01). After 24 hr, we observed no difference in viability despite ATP concentration differences. However after 48 hr preservation, graft viability varied among the groups: 0/4 (0%), 4/4 (100%), and 0/3 (0%) in groups 1b, 2b, and 3b, respectively. ATP tissue concentration was again higher in group 2b after two-layer (EC/PFC) method preservation (7.91 +/- 1.21 vs. 1.21 +/- 0.31 mumol/g dry weight, P less than 0.01) compared with EC preservation (group 1b). DNP again caused a significant decrease in tissue ATP in group 3b (0.61 +/- 0.07 vs. 7.91 +/- 1.21, P less than 0.01). The two-layer (EC/PFC) method clearly protected pancreas viability, and inhibition of ATP production using DNP caused loss of viability in this model. We conclude that oxygenation of the pancreas during preservation by the two-layer method allows continued ATP production within the graft. Metabolic processes vital to cellular integrity can be maintained, which produces an extended period of preserved pancreatic viability.

2,4-Dinitrophenol↗