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Elevated amylase creatinine clearance ratio and normal serum amylase levels in chronic relapsing pancreatitis after partial pancreatectomy.

A 29-year-old woman admitted for alcohol detoxification five years after a 90% distal pancreatectomy for chronic pancreatitis had abdominal pain similar to that associated with preoperative pancreatitis. Although her clinical course was consistent with recurrent pancreatitis, the serum amylase level remained normal, but the amylase creatinine clearance ratio became elevated and then returned to normal, paralleling her clinical course. The ACCR may be a useful laboratory method in diagnosing chronic recurrent pancreatitis in patients with decreased functional pancreatic tissue.

Adult↗

Laparoscopic spleen-preserving pancreatectomy for traumatic pancreatic transection: a case report.

Pancreatic transection from blunt trauma is uncommon. A 33-year-old woman suffered from blunt pancreatic trauma after a traffic accident. Computed tomography of the abdomen showed full thickness laceration through the body of the pancreas. She underwent laparoscopic spleen-preserving pancreatectomy with minimal morbidity. She remained well and without any complications 4 years after the operation.

Accidents, Traffic↗

Pancreatectomy with islet autotransplantation for the treatment of severe chronic pancreatitis: the first 40 patients at the leicester general hospital.

BACKGROUND: Surgical resection of the pancreas is considered a final resort in the treatment of chronic pancreatitis. However, the opportunity to perform an islet autotransplant at the same time provides the potential to prevent the onset of diabetes. METHODS: Pancreatectomy together with islet autotransplantation has been offered in our center since 1994. A total of 40 patients have now undergone this procedure. The follow-up times range from 6 months to 7 years. The data presented here include the annual postoperative oral glucose tolerance test and glycosylated hemoglobin (HbA(1c)) results, together with insulin and opiate requirements. RESULTS: Nineteen male and 21 female patients (median age 44, range 21-65) have been transplanted. Pancreatitis was related to alcohol in 45% and was idiopathic in 40%. A median of 130108 (24332-1, 165538) islet equivalent (IEQ) were transplanted, which related to 2020 (320-23311) IEQ per kilogram of body weight. At 2 years posttransplant, 18 patients had a median HbA(1c) of 6.6% (5.2-19.3%), fasting C-peptide of 0.66 ng/mL (0.26-2.65 ng/mL), and required a median of 12 (0-45) units of insulin per day. At 6 years, these figures were 8% (6.1-11.1%), 1.68 ng/mL (0.9-2.78 ng/ml) and 43 U/day (6-86 U/day), respectively. The majority of patients no longer require opiate analgesia, 68% have been able to return to work, and one patient has had a baby. CONCLUSIONS: Islet autotransplantation offers a valuable addition to surgical resection of the pancreas, as a treatment for chronic pancreatitis; and even in cases in which insulin independence is not achieved, the potential beneficial effects of C-peptide make the procedure worthwhile.

Adult↗

A comparison of two methods of partial pancreatectomy in the dog.

Partial pancreatectomy was performed in 9 dogs by dissection and ligation of the pancreatic ductule and blood vessels, and in 10 dogs by a suture fracture technique. The dogs were evaluated for detrimental effects by (1) monitoring clinical signs and serum amylase and lipase activities and (2) examining the excision sites grossly and histologically at necropsy. There were no clinically apparent detrimental effects with either technique. The suture fracture technique evoked more histologic inflammation than the dissection and ligation technique.

Amylases↗

The effects of pancreatectomy on the sheep fetus in utero.

The effects of the removal of the fetal pancreas on the fetal metabolite concentrations and body weight have been investigated in chronically catheterized sheep fetuses during the last third of gestation. Between 390 and 1175 mg of pancreatic tissue was removed under halothane anaesthesia from sixteen fetuses between 113 and 121 d of gestation (term = 147 +/- 2d). In six fetuses from which 928 +/- 58 mg of pancreas had been removed the insulin level (3.4 +/- 0.3 micro micron/ml, n = 6) was below or equal to the limit of sensitivity of the assay. As only very small pieces of pancreas, if any, could be found in these fetuses at delivery, removal of the pancreas was regarded as complete in these animals. Pancreatectomy was incomplete in five fetuses from which 659 +/- 62 mg of pancreas had been removed. Insulin was detected in the plasma of these fetuses although the mean concentration (9.1 +/- 0.7 micro micron./ml, n = 5) significantly less than that in sham-operated animals (P less than 0.01). Small fragments of pancreas (0-26 mg) containing endocrine cells were found in these fetuses at delivery. Fetuses from which less than 50% of the pancreas had been removed had plasma insulin and metabolite concentrations similar to those of the sham-operated fetuses. Significant amounts of histologically normal pancreas were found in these fetuses at delivery. The plasma concentrations of glucose, fructose and alpha-amino nitrogen were significantly greater in the incompletely and completely pancreatectomized fetuses than in the sham-operated animals (P less than 0.01). In addition, the completely pancreatectomized animals also had higher plasma levels of lactate and free fatty acids than the sham-operated fetuses (P less than 0.01). There were no significant differences in the urea concentrations between sham-operated and pancreatectomized fetuses, but the fetal to maternal concentration difference in arterial plasma urea was greatest in the completely pancreatectomized fetuses (P less than 0.05). The hypoinsulinaemic fetuses were significantly smaller in birth weight than the sham-operated animals (P less than 0.02). The results show that removal of about 70% of the fetal pancreas will produce hypoinsulinaemia in the fetus and confirm that the pancreas is essential for normal growth and development in utero.

Animals↗

The effect of pancreatectomy and other agents on iron absorption and storage in the rat.

Evidence from both animal and human studies had been presented by various authors to suggest that reduction of pancreatic function increased iron absorption. The present experimental studies in rats showed that there was increased radioiron ((59)Fe) absorption after pancreatectomy, but this appeared to be due to the operative procedure as there was a similar increased absorption in animals who had sham operations performed. There was no certain evidence that pancreatic enzymes or extract had a specific inhibitory effect on the absorption of iron. But with increased doses of pancreatic extract, above the normal doses, the amount of radioiron absorption was greatly enhanced.A significant increase in hepatic storage iron was found in the groups of rats who had been fed a diet supplemented with dl-ethionine. All these animals showed extensive damage and atrophy of the pancreas, with degeneration and considerable regenerative activity in the liver. The absolute increased hepatic storage iron was not due to the liberation and laying down of haemosiderin from the damaged cells or to decreased liver mass. Rats who had carbon tetrachloride-induced liver cirrhosis without pancreatic damage showed no increased hepatic storage iron. It was observed that in liver damage with considerable cellular proliferation there was increased liver iron content. As this was found only when there was associated pancreatic injury, it is suggested that decreased pancreatic function in the presence of liver cell injury with cellular proliferation leads to increased iron absorption and storage. The relationship of liver injury with cellular proliferation and pancreatic damage to increased hepatic storage iron merits further study.

Absorption↗

Undernutrition does not alter the activation of beta-cell neogenesis and replication in adult rats after partial pancreatectomy.

In previous work, we demonstrated that a 65% protein calorie food restriction started during the third trimester of gestation in rats caused a reduced beta-cell mass at 4 days of life that persisted until adult age. In this study with adult undernourished (U) rats, we investigated 1) whether undernutrition affects the beta-cell growth potential and both beta-cell proliferation and differentiation and 2) the implication of the IGFs, highly responsive to nutritional status, in these processes. To this end, we used the 90% pancreatectomy (Px) procedure in U and control (C) adult rats. The results show that, on day 2 after Px, beta-cell replication was significantly higher in C rats, whereas the beta-cell neogenesis was markedly increased in U/Px rats. Both the serum levels of IGF-I and the liver IGF-I mRNA expression were reduced in adult U rats before and after Px compared with C rats. Pancreatic IGF-I mRNA expression was reduced in U animals on day 0. However, on day 2 after Px, the increase of pancreatic IGF-I mRNA expression was significantly higher in U rats than in C rats. These data suggest that beta-cells still have the capacity to regenerate in the adult U rats, with a higher efficiency than C rats on day 2, and that both beta-cell neogenesis and beta-cell replication are stimulated. The increased pancreatic IGF-I mRNA may be instrumental in these processes.

Age Factors↗

beta-cell adaptation in 60% pancreatectomy rats that preserves normoinsulinemia and normoglycemia.

Islet beta-cells are the regulatory element of the glucose homeostasis system. When functioning normally, they precisely counterbalance changes in insulin sensitivity or beta-cell mass to preserve normoglycemia. This understanding seems counter to the dogma that beta-cells are regulated by glycemia. We studied 60% pancreatectomy rats (Px) 4 wk postsurgery to elucidate the beta-cell adaptive mechanisms. Nonfasting glycemia and insulinemia were identical in Px and sham-operated controls. There was partial regeneration of the excised beta-cells in the Px rats, but it was limited in scope, with the pancreas beta-cell mass reaching 55% of the shams (40% increase from the time of surgery). More consequential was a heightened glucose responsiveness of Px islets so that glucose utilization and insulin secretion per milligram of islet protein were both 80% augmented at normal levels of glycemia. Investigation of the biochemical basis showed a doubled glucokinase maximal velocity in Px islets, with no change in the glucokinase protein concentration after adjustment for the different beta-cell mass in Px and sham islets. Hexokinase activity measured in islet extracts was also minimally increased, but the glucose 6-phosphate concentration and basal glucose usage of Px islets were not different from those in islets from sham-operated rats. The dominant beta-cell adaptive response in the 60% Px rats was an increased catalytic activity of glucokinase. The remaining beta-cells thus sense, and respond to, perceived hyperglycemia despite glycemia actually being normal. beta-Cell mass and insulin secretion are both augmented so that whole pancreas insulin output, and consequently glycemia, are maintained at normal levels.

Adaptation, Physiological↗

Identification of transcriptional targets during pancreatic growth after partial pancreatectomy and exendin-4 treatment.

After partial pancreatectomy (Ppx), substantial regeneration of the endocrine and exocrine pancreatic compartments has been shown in adult rodents. Exendin-4 (Ex-4) is a glucagon-like peptide-1 receptor agonist that augments endocrine beta-cell mass by stimulating neogenesis, proliferation, and cell survival. After Ppx, treatment with Ex-4 ameliorates hyperglycemia by stimulating beta-cell mass recovery. We utilized a cDNA microarray approach to identify genes differentially regulated during pancreatic regeneration after Ppx and/or Ex-4 administration. The pancreatic remnant after Ppx showed a large number of differentially regulated genes. In contrast, Ex-4 treatment resulted in a smaller number of differentially regulated genes. Of note, a common subset of genes regulated by Ex-4 and after Ppx was identified, including three members of the mitogenic Reg gene family, Reg2, -3gamma, and -3beta, as well as fragilis, a gene that maintains pluripotency during germ cell specification, and Serpin b1a, a member of an intracellular protease inhibitor family involved in cell survival. These observations were confirmed by real-time PCR. We determined that Reg3beta protein is also induced in the acinar pancreas after Ppx, suggesting a novel role for this factor in pancreatic growth or response to injury. Finally, comparison of transcription factor-binding sites present in the proximal promoters of these genes identified potential common transcription factors that may regulate these genes. Chromatin immunoprecipitation analyses confirmed Reg3gamma as a novel transcriptional target of Foxa2 (HNF3beta). Our data suggest molecular pathways that may regulate pancreatic growth and offer a unique set of candidate genes to target in the development of therapies aimed at improving pancreatic growth and function.

Animals↗

Pancreaticogastrostomy after subtotal pancreatectomy for cancer.

BACKGROUND: Failure of the pancreaticodigestive anastomosis after pancreatoduodenectomy is still a major clinical problem. Pancreaticogastrostomy has recently been suggested to be associated with a low risk of leakage. The aim of this report was to add to previously reported experience. METHODS: Data on the postoperative course were prospectively registered in 19 patients operated on with subtotal pancreatectomy because of periampullary cancer. They all had a duct-to-mucosa pancreaticogastrostomy. RESULTS: There were no recognizable leakages from the pancreaticogastrostomy. However, the overall postoperative complication rate was 47% (9/19), the most common complications being delayed gastric emptying (26%, 5/19), wound infection (21%, 4/19), and wound rupture (11%, 2/19). Excluding delayed gastric emptying, the rate of intra-abdominal complications was 16% (3/19). There was 1 in-hospital death. CONCLUSION: The results support the opinion that pancreaticogastrostomy can be done with a low risk of leakage.

Aged↗

Evaluation of splenic circulation after spleen-preserving distal pancreatectomy by dividing the splenic artery and vein.

BACKGROUND/AIM: In the present study, we investigated the acute and late phases of splenic circulation after spleen-preserving distal pancreatectomy (SPDP) involving the division of splenic vessels. METHODS: An acute phase of splenic circulation was evaluated by laser flow meter and the late phase was estimated by (99m)Tc-galactosyl human serum albumin spleen scintigraphy. RESULTS: Splenic blood supply, evaluated by laser flow meter immediately after SPDP, dropped to one half of the prior blood supply. However, blood supply recovered 10 days after SPDP, as estimated by (99m)Tc-galactosyl human serum albumin spleen scintigraphy. CONCLUSION: There are two variations of SPDP: SPDP without preservation of the splenic artery and vein, and SPDP with preservation of the splenic artery and vein. The disadvantage of the former is the resulting decrease in splenic blood supply. The present findings may help to make up for this disadvantage.

Humans↗

Central pancreatectomy for a pancreatic ganglioneuroma in a patient with previous neuroblastoma.

This is a case presentation of a 28-year-old woman with a mass at the junction of the neck and the body of the pancreas and a childhood history of a resected adrenal neuroblastoma. A central pancreatectomy was performed in this patient. The pathology revealed a benign ganglioneuroma. Ganglioneuromas and their association with a neuroblastoma are briefly reviewed. The indications and contraindications for, as well as the advantages and disadvantages of, a central pancreatic resection are discussed.

Adult↗

A resected case of multiple intraductal papillary mucinous tumors of the pancreas with US-guided ductal branch-oriented partial pancreatectomy.

A 69-year-old man with epigastralgia was admitted on August 26, 2002 and diagnosed with multiple intraductal papillary mucinous tumors by various imagings. The cystic tumor of pancreas head had a diameter of 2 cm, and the mural nodule of the cystic tumor measured only 3 mm. In the pancreas body the cystic tumor was measured at 1.5 cm with the mural nodule of the cystic tumor measuring 3 mm. It was believed that the tumors were benign. However, a mural nodule of the cystic lesion was recognized, thus, the possibility of malignancy could not be completely ruled out. The reduction operation for preservation of pancreatic parenchyma should be selected for these circumstances. Ductal branch-oriented partial pancreatectomy was performed on September 6, 2002 with intraoperative ultrasonography and a Cavitron Ultrasonic Aspirator, preserving the main pancreatic duct and normal pancreatic parenchyma. The operation was successful, and the histopathological diagnosis of the tumors was intraductal papillary adenoma of the pancreas.

Adenoma↗

Partial pancreatectomy in the rat and subsequent defect in glucose-induced insulin release.

To define the consequences of a known reduction of B cell mass in rats, 90% partial pancreatectomies were performed. For the 6 wk following surgery moderate hyperglycemia was maintained in the fed state but there were no differences in body weight nor plasma insulin concentrations compared with sham-pancreatectomized controls. 8-10 wk following surgery regeneration of the remnant was evident with remnant weight being 26%, B cell mass being 42%, and non-B cell mass being 47% of values found for control whole pancreas. There were comparable increases in the remnant content of insulin, glucagon, and somatostatin. Following meal challenges, intraperitoneal and intravenous glucose tolerance tests and intravenous arginine challenge given 6-7 wk after surgery, the insulin responses to glucose were blunted or absent but the responses following the meals or arginine were intact. Similarly, when the pancreatic remnant was perfused in vitro, insulin release after challenge with 300 mg/dl glucose was markedly reduced whereas intact responsiveness to 10 mM arginine was retained. These data suggest that the chronic stimulation of a reduced B cell mass can lead to a selective loss of glucose-induced insulin secretion.

Animals↗

Minimal chronic hyperglycemia is a critical determinant of impaired insulin secretion after an incomplete pancreatectomy.

We now describe experiments that allow one to determine the consequences of B cell reduction alone vs. those that result from superimposed mild hyperglycemia. Male CD rats underwent a 60% pancreatectomy (Px); controls were sham operated. 1 wk later, either 10% sucrose (SUC) was substituted as fluid supply or tap water was continued (WAT). Plasma glucose and insulin values in Px-WAT remained equal to the sham groups; in Px-SUC the values were euglycemic for 25 d, but then nonfasting plasma glucose rose 15 mg/dl. After 6 wk, B cell mass in Px-WAT was reduced by 45% and non-B cell mass by 57%. In contrast, in Px-SUC both masses were comparable to the sham groups. The insulin response to 27.7 mM glucose was measured using the in vitro perfused pancreas. The responses were reduced in Px-WAT but in proportion to their reduced B cell mass; in contrast, it was 75% less than expected in Px-SUC. Also, the response to arginine given at 16.7 mM glucose was reduced only in Px-SUC. These results show that a lowering of B cell mass that does not result in hyperglycemia has no adverse effect on the remaining B cells. On the other hand, if even mild hyperglycemia develops, B cell function becomes impaired and results in inappropriately reduced insulin stores and insulin responses to marked stimuli.

Animals↗