Pancreatic Venous Research Articles

Pressure-enabled delivery of gemcitabine in an orthotopic pancreatic cancer mouse model

BackgroundWe describe the use of pancreatic retrograde venous infusion in an orthotopic murine model of pancreatic ductal adenocarcinoma and hypothesize that pancreatic retrograde venous infusion delivery of gemcitabine will increase concentrations of gemcitabine in the tumor and the subsequent tumor response to treatment. MethodsMurine pancreatic ductal adenocarcinoma (KPC4580P) was transplanted onto the pancreatic tail of C57BL/6J mice. Groups (n = 15) of mice were assigned to sham laparotomy and 100 mg/kg intraperitoneal infusion of gemcitabine (systemic gemcitabine), pancreatic venous isolation with pancreatic retrograde venous infusion of 100 mg/kg gemcitabine, or pancreatic retrograde venous infusion with saline infusion. Tumor pressures were recorded during pancreatic retrograde venous infusion. Mice were killed at 1 hour or 7 days after infusion. ResultsBaseline tumor pressures were 45 ± 8 mm Hg, and pancreatic retrograde venous infusion increased tumor pressures by 29 ± 6 mm Hg (P < .01). Pancreatic retrograde venous infusion gemcitabine mice had greater tumor gemcitabine concentrations compared with systemic gemcitabine (127 vs 19 ng/mg; P < .01) and lesser tumor volumes compared with both systemic gem and pancreatic retrograde venous infusion with saline (274 vs 857 vs 629 mm3; P < .01). ConclusionPancreatic retrograde venous infusion increased tumor pressures greater than baseline, improved gemcitabine delivery, and increased the treatment response. These findings suggest that pressurized, regional delivery overcomes the increased pressure barrier in pancreatic ductal adenocarcinoma. Additional preclinical studies with cytotoxic and immunotherapeutic agents and clinical trials using pressure-enabled drug delivery with pancreatic retrograde venous infusion devices are underway.

Glucose-Dependent Insulinotropic Polypeptide Is a Pancreatic Polypeptide Secretagogue in Humans.

Glucose-dependent insulinotropic polypeptide (GIP) has been suggested to stimulate the secretion of pancreatic polypeptide (PP), an islet hormone thought to regulate gut motility, appetite, and glycemia. To determine whether human GIP1-42 (hGIP) stimulates PP secretion. As glycemia modulates the secretion of PP, we measured plasma PP concentrations from 2 studies in healthy men (n = 10) and in patients with type 2 diabetes (T2D) (n = 12), where hGIP1-42 had been administered intravenously during fasting glycemia, hyperglycemia (12 mmol/L), and insulin-induced hypoglycemia (targets: 2.5 mmol/L [healthy]; 3.5 mmol/L [T2D]). Porcine GIP1-42 (pGIP) was also infused intra-arterially in isolated porcine pancreata (n = 4). Mean fasting plasma glucose concentrations were approximately 5 mmol/L (healthy) and approximately 8 mmol/L (T2D). At fasting glycemia, PP concentrations were higher during intravenous hGIP1-42 infusion compared with saline in healthy men (mean [standard error of the mean, SEM], net incremental areas under the curves (iAUCs)[0-30min], 403 [116] vs -6 [57] pmol/L × min; P = 0.004) and in patients with T2D (905 [177] vs -96 [86] pmol/L × min; P = 0.009). During hyperglycemic clamping, mean [SEM] PP concentrations were significantly higher during hGIP1-42 infusion compared with saline in patients with T2D (771 [160] vs -183 [117] pmol/L × min; P = 0.001), but not in healthy individuals (-8 [86] vs -57 [53] pmol/L × min; P = 0.69). When plasma glucose levels were declining in response to exogenous insulin, mean [SEM] PP concentrations were higher during hGIP1-42 infusion compared with saline in healthy individuals (294 [88] vs -82 [53] pmol/L × min; P = 0.0025), but not significantly higher in patients with T2D (586 [314] vs -120 [53]; P = 0.070). At target hypoglycemia, PP levels surged in both groups during both hGIP1-42 and saline infusions. In isolated pancreata, pGIP1-42 increased mean [SEM] PP output in the pancreatic venous effluent (baseline vs infusion, 24[5] vs 79 [16] pmol/min x min; P = 0.044). GIP1-42 increases plasma PP secretion in healthy individuals, patients with T2D, and isolated porcine pancreata. Hyperglycemia blunts the stimulatory effect of hGIP1-42 in healthy individuals, but not in patients with T2D.

COMPARATIVE ANALYSIS IMAGE RESULTS OF PANCREAS IN PORTAL VEIN PHASE ON CT SCAN ABDOMEN CONTRAST WITHOUT AND WITH MINIMUM INTENSITY PROJECTION IN CT SCAN 64 SLICE

Background: Minimum Intensity Projection is a post-proccesing technique on CT Scan that useful for showing structures with low Hounsfiled Unit (HU) values such as pancreas. To demonstrate the anatomy and pathology of the pancreatic organs, a contrast CT scan was performed on pancreatic phase but pancreatic phase was rarely used, so it was replaced by the portal venous phase, but this technique is still rarely used among the radiographers. Objective: This study aimed to prove the image of the portal venous pancreatic vein on contrast contrast CT scan by using minimum intensity projection (MinIP) on CT scan 64 slices will produce a more optimal image than without the minimum intensity projection (MinIP). Methods: This study is a retrospective study with an observational analytic method to assess differences of pancreatic image in contrasting contrast CT scans with and with MinIP reforms on CT 64 slice modalities Philips Briliance. 30 images as samples, with the criteria set by the researchers. The image will be post proccesing without and by using MinIP reformat. Image results will be evaluated by two radiologist, then the data obtained will be tabulated and processed using SPSS software version 17. Result: From this research obtained the result that MinIP reformat able to produce pancreas image more optimal than image without MinIP reformat on CT scan 64 slice and shows a significant difference. Overall assessment of the image has an improvement with the MinIP but for the homogeneity of pancreatic images decreased. Conclusions: There was a significant difference between pancreatic venous porta port results in contrasting CT scans of the abdomen without and with MinIP reformat.

Cellular and stromal elements organization in the liver of grass carp, Ctenopharyngodon idella (Cypriniformes: Cyprinidae)

Fish liver is considered as a key organ that controls various life functions. The cellular and stromal elements of liver of eighteen specimens of adult grass carp were investigated by light- and electron- microscopy and enzyme histochemistry. The liver was formed of two lobes with a long process extended from the right lobe. Serial paraffin section of the liver identified different kinds of vascular- biliary structures as follows: 1) pancreatic–venous–biliary–arteriolar tracts (P-VBAT); 2) venous-biliary-arteriolar tracts, (VBAT); 3) pancreatic–venous–biliary tracts (P-VBT); 4) venous-biliary tracts (VBT); 5) venous–arteriolar tracts (VAT); 6) isolated veins named as venous tracts (VT); 7) isolated bile ducts, named as biliary tracts (BT); 8) biliary-arteriolar tracts (BAT); 9) pancreatic–biliary tracts (P-BT); 10) pancreatic– venous tracts (P-VT). Macrophages aggregates were associated with VBT and P-BT. The hepatic parenchyma was consisted of many populations of cells. Histochemically, the hepatocytes were strongly reacted with PAS, and Best's carmine. Moreover, strong staining patterns for acid phosphatase, ATPase, and alkaline phosphatase were demonstrated in hepatocytes. The hepatic satellate (Ito) cells were observed in the space of Disse and between hepatocytes. Rodlet cells and eosinophilic granular/ mast cells were encountered in the liver of grass carp. The sinusoids were lined by fenestrated endothelial cells and Kupffer cells. Moreover, dendritic-like cells were demonstrated in the sinusoids and perisinusoidal connective tissue. The biliary duct system was constituted of bile canaliculi, ductules, and bile ducts. Telocytes with their characteristics telopodes were located around bile ducts. The current findings are offering fundamental data on histology of grass carp liver.

Sensitivity to insulin and its kinetics.

Sensitivity to insulin and its kinetics.

A Rare Cause of Diarrhea in a Crohnʼs Patient: Pancreatic Insufficiency Due to Portal Vein Thrombosis

Inflammatory bowel disease (IBD) is an inflammatory state with an increased risk of venous thromboembolism (VTE). Patients with IBD have a three-fold higher risk of VTE compared to patients without IBD. This may occur due to disequilibrium between procoagulant and anticoagulant factors, bacterial translocation leading to portal pylephlebitis, or post-operative state. Herein, we present a case of Crohn's disease with portal vein thrombosis (PVT) causing exocrine pancreatic insufficiency (EPI). A 44 year-old man with fistulizing and fibrostenosing Crohn's Disease since age 12 presented with more than 10 bowel movements daily for 1 month. He was previously treated with adalimumab for 4 years without improvement in subjective symptoms, thus the patient self-discontinued medication at age 40. One year prior to presentation, the patient had severe abdominal pain and was found to have a peri-anal fistula and mid-transverse colonic stricture. He underwent an elective resection of 14.5 cm of his transverse colon with ileo-colonic anastomosis. On post-operative imaging, he was found to have PVT and completed 3 months of lovenox. Three months post-operative, he developed frequent non-bloody post-prandial diarrhea with early satiety and vague abdominal discomfort. He was tried on cholestyramine with minimal improvement. An EGD and colonoscopy to evaluate the diarrhea were non-diagnostic. He was sent for a CT scan to rule out small bowel to colonic fistula and was found to have extension of his portal vein thrombus from the left hepatic vein to the splenic vein. In addition, the CT scan showed atrophy of hepatic segments 6 and 7, but no evidence of pancreatitis. CBC and serum tryptase were unremarkable. He had an elevated AST, ALT, and alkaline phosphatase. He was started on pancrelipase and long-term anticoagulation with rivaroxaban with rapid improvement in symptoms consistent with EPI due to extension of the PVT into venous drainage of the pancreas. Active IBD is a risk factor for VTE. Here we describe a rare case of persistent diarrhea in a patient with Crohn's disease due to EPI associated with PVT. This has rarely been described in the literature, but the pathophysiology is thought to be due to PVT leading to obstruction of pancreatic venous drainage, causing pancreatic duct atrophy and exocrine insufficiency. Thus, in IBD patients with a history of PVT and persistent diarrhea it is important to consider EPI as an etiology.

Are there still roles for exocrine bladder drainage and portal venous drainage for pancreatic allografts?

Controversy remains regarding the best methodology of handling exocrine pancreatic fluid and pancreatic venous effluent. Bladder drainage has given way to enteric drainage. However, is there an instance in which bladder drainage is preferable? Also, hyperinsulinemia, as a result of systemic venous drainage (SVD), is claimed to be proatherosclerotic, whereas portal venous drainage (PVD) is more physiologic and less atherosclerotic. Bladder drainage remains a viable method of exocrine pancreas drainage, but evidence is sparse that measuring urinary amylase has a substantial benefit in the early detection of acute rejection in all types of pancreas transplants. Currently, there is no incontrovertible evidence that systemic hyperinsulinemia is proatherosclerotic, whereas recent metabolic studies on SVD and PVD showed that there was no benefit to PVD. Given the advent of newer immunosuppressive agents and overall lower acute rejection rates, the perceived benefit of bladder drainage as a means to measure urinary amylase as an early marker of rejection has not been substantiated. However, there may be a selective role for bladder drainage in 'high risk' pancreases. Also, without a clear-cut metabolic benefit to PVD over SVD, it remains the surgeon's choice as to which method to use.

Trypsin is the culprit of multiple organ injury with severe acute pancreatitis

The consistently high proportion of early deaths in patients with severe acute pancreatitis (SAP) has been associated mainly with the development of multiple organ dysfunction syndromes (MODS). So far, scholars believed that the main reasons of MODS with SAP are systemic microcirculation dysfunction and inflammatory mediator induced cascading effect on the basis of pancreas digesting itself. However, there is some special pathological phenomenon in the process of SAP which could not be explained by current theories. First, it has been evident that the pancreatic tissue bleeding and necrosis is special pathological change in pancreas autodigestive effect from digestive enzymes such as trypsin in SAP. However, we found that the liver, the lung, the intestine, the brain and the kidney have the same pathological changes in experimental animal models of SAP. Secondly, unlike the general inflammatory response, a significantly amount of bloody ascites and pleural effusion was often in patients with SAP and in experimental SAP animal models. It indicates that the vascular permeability significantly increased leading to the red blood cells extravasation. Thirdly, apart from dual blood supply, liver bears a strong compensatory function. However, liver has the highest incidence of injury in SAP when compared with other organs. In addition, we found a very interesting phenomenon after reading texts and clinical records. From the pancreatic venous drainage from the point of view, the farther the organ from the pancreas, the lower injury incidence rate observed. How to explain these mysteries? We postulate that the trypsin is the culprit of multiple organs dysfunction in SAP. The activated trypsin destroy the pancreas itself, causing pancreatic tissue bleeding and necrosis, at the same time, through venous flow it flow into the blood circulation and destroy the vascular endothelial barrier, leading to highly increased vascular permeability. So, a large number of bloody exudates leakages from the vessels, resulting in patients early circulatory disorders, multiple organ bleeding, bloody pleural effusion and ascites. This pathological change is the most apparent in the liver because the liver is the first organ to receive the pancreatic venous flow having the highest concentration of trypsin. Thus, if the quantity of trypsin decreases in blood, its ability to damage other organs also shows a trend of gradually reducing. These mysteries can be explained by this hypothesis and might help us to understand more clearly about the mechanism of SAP-associated MODS.

Impact of pancreatic venous drainage site on long‐term patient and graft outcome in simultaneous pancreas‐kidney transplantation

The impact of portal or systemic venous pancreas graft drainage on patient and graft outcome remains controversial. In the present study, the impact of venous drainage type on long-term patient and graft survival is assessed. From July 1996 to December 2002 80 simultaneous pancreas-kidney transplants were enrolled into a prospective study: 44 received a pancreas allograft with portal (P-SPK group) and 36 with systemic venous drainage (S-SPK group). Enteric exocrine drainage was performed in all recipients receiving the same immunosuppressive treatment. At one yr, the patient survival rates were 91.7% and 95.5% both for S-SPK and P-SPK groups, respectively; no significant difference in survival was shown at any time point of the follow-up. The one-, three-, five-, and eight-yr pancreas survival rates were 75%, 60.6%, 56.7%, and 44%, respectively in the S-SPK group compared to 88.6%, 84.1%, 78.4%, and 31.3% in the P-SPK group. The one-, three-, five-, and eight-yr kidney survival rates were 91.7%, 78.15%, 74.1%, and 57.9%, respectively in the S-SPK group compared to 93.2%, 88.6%, 78.4%, and 38.9% in the P-SPK group. Comparing the two groups, no significant difference was shown in the total number of surgical complications as well as in the number of each complication. No significant difference in long-term outcomes between the two groups was shown, even if in S-SPK group a higher incidence of pancreas graft loss has been reported and it was in part correlated to a higher number of graft thromboses.

Catheter‐directed therapy for DVT after pancreas transplantation

Iliac vein deep venous thrombosis (DVT) ipsilateral to the pancreas transplant can lead to severe leg edema and compromise graft function. Treatment modalities for iliac vein DVT in the pancreas transplant recipient are limited. Medical records of patients receiving pancreas transplants at a single center from November 1989 to July 2003 were reviewed retrospectively, identifying patients with iliac vein DVT. There were 287 pancreas transplants performed during this time. Pancreas transplantation in all recipients was performed in the right iliac fossa with the arterial supply consisting of a donor iliac artery Y interposition graft. Systemic venous drainage was to the iliac vein. Exocrine drainage was enteric or to the bladder. Four (1.4%) cases of iliac DVT were identified. All patients manifested lower extremity edema ipsilateral to the pancreas transplant. DVT was detected by ultrasound on days 4, 5, 13, and 60 post-transplant. In all cases, the iliac vein caudad to the pancreatic venous anastomosis was noted to be stenotic. Management involved balloon dilatation and endovascular stent placement in one patient, thrombolysis with tissue plasma antigen (t-PA) followed by stent placement in one patient, and percutaneous mechanical thrombectomy in two patients. All patients had improvement in leg edema and two patients continue to have good pancreatic allograft function. Iliac DVT is a rare complication of pancreas transplantation that usually develops in an area of stenosis caudad to the pancreatic venous anastomosis. Catheter-based treatment modalities with use of endovascular stents for treatment of underlying stenoses can serve as an adjunct in treating these complications.

The added value of [18F]fluoro-L-DOPA PET in the diagnosis of hyperinsulinism of infancy: a retrospective study involving 49 children

Neuroendocrine diseases are a heterogeneous group of entities with the ability to take up amine precursors, such as L-DOPA, and convert them into biogenic amines, such as dopamine. Congenital hyperinsulinism of infancy (HI) is a neuroendocrine disease secondary to either focal adenomatous hyperplasia or a diffuse abnormal pancreatic insulin secretion. While focal hyperinsulinism may be reversed by selective surgical resection, diffuse forms require near-total pancreatectomy when resistant to medical treatment. Here, we report the diagnostic value of PET with [(18)F]fluoro-L-DOPA in distinguishing focal from diffuse HI. Forty-nine children were studied with [(18)F]fluoro-L-DOPA. A thoraco-abdominal scan was acquired 45-65 min after the injection of 4.2 +/- 1.0 MBq/kg of [(18)F]fluoro-L-DOPA. Additionally, 12 of the 49 children were submitted to pancreatic venous catheterisation for blood samples (PVS) and 31 were also investigated using MRI. We identified abnormal focal pancreatic uptake of [(18)F]fluoro-L-DOPA in 15 children, whereas diffuse radiotracer uptake was observed in the pancreatic area in the other 34 patients. In children studied with both PET and PVS, the results were concordant in 11/12 cases. All patients with focal radiotracer uptake and nine of the patients with diffuse pancreatic radiotracer accumulation, unresponsive to medical treatment, were submitted to surgery. In 21 of these 24 patients, the histopathological results confirmed the PET findings. In focal forms, selective surgery was followed by clinical remission without carbohydrate intolerance. These data demonstrate that PET with [(18)F]fluoro-L-DOPA is an accurate non-invasive technique allowing differential diagnosis between focal and diffuse forms of HI.

Carbohydrate tolerance with portal and systemic venous drainage of the pancreas.

Carbohydrate tolerance was studied in 8 dogs with pancreatic venous drainage to the hepatic portal vein and 6 dogs with pancreatic venous drainage to the systemic veins. While systemic venous drainage of the pancreas was associated with higher fasting plasma insulin and lower fasting plasma glucose levels, no significant differences in either glucose clearance or insulin response to glucose were detectable. Therefore, in the maintenance of plasma glucose homeostatis, administration of insulin into the portal vein offers no significant advantages over the easier systemic route.

Treatment and outcome of pancreatic venous graft thrombosis after kidney--pancreas transplantation.

Pancreas venous graft thrombosis after transplantation is the main non-immunological cause of graft failure and usually results in pancreatectomy. Duplex Doppler ultrasonography is the primary imaging technique for monitoring vascular patency after pancreas transplantation. This study reports the results of rescue treatments for pancreas graft thrombosis after simultaneous pancreas--kidney transplantation. One hundred and ninety-six patients with insulin-dependent diabetes mellitus received a simultaneous pancreas--kidney transplantation. Venous graft thrombosis was diagnosed in 25 of these patients based on Doppler ultrasonographic findings. Total venous graft thrombosis was diagnosed in 20 symptomatic patients, of whom 14 required graft pancreatectomy. Surgical thrombectomy was attempted in six patients with preserved arterial supply and was successful in four. Partial venous graft thrombosis was diagnosed in five asymptomatic patients; one also had partial splenic artery thrombosis. Rescue graft procedures included systemic anticoagulation (one patient), arterial thrombolysis (one) and venous thrombolysis and/or mechanical venous thrombectomy (four episodes in three patients). Graft rescue was achieved in three patients treated by venous thrombolysis/thrombectomy. Doppler ultrasonography allows the appropriate selection of rescue treatment based on the findings of total or partial thrombosis.

Beta-cell mass and site of pancreatic venous drainage are independent determinants of the suppression of endogenous glucose production and systemic insulin sensitivity during glucose loading

Beta-cell mass and site of pancreatic venous drainage are independent determinants of the suppression of endogenous glucose production and systemic insulin sensitivity during glucose loading

Intragastric alcohol causes endothelin release from feline pancreas.

The mechanism by which alcohol causes pancreatic damage is still largely unknown. One important contributory factor may be the endothelins, potent vasoconstricting endothelial-derived peptides. The aim of this study was to examine in vivo endothelin release from the pancreatic vascular endothelium after alcohol ingestion. In anesthetized cats immunoreactive endothelin was measured in serum after instillation of alcohol into the stomach (20 ml, 40%). After intragastric alcohol, a rise in endothelin was seen in pancreatic venous effluent (to a mean of 24.5 +/- 7.7 pg/ml at 60 min). Control serum from the femoral artery exhibited no rise in endothelin (2.11 +/- 1.2 pg/ml). Pancreatic blood flow was significantly decreased in a further group to 93% basal after intravenous infusion of 0.1 nmol/kg ET-1 and to 61% after infusion of 1 nmol/kg ET-1. Portal serum levels of endothelin were 105 pg/ml and 15 pg/ml, respectively, immediately following bolus infusion and decreased to normal levels within 120 sec. We conclude that the serum endothelin rise after intragastric ethanol may be a major factor behind the drop in pancreatic blood flow.

Portal insulin delivery is superior to peripheral delivery in handling of portally delivered glucose

It is still controversial as to whether physiological portal insulin delivery has metabolic advantages over peripheral insulin delivery. To clarify this issue, glycemic regulation during intravenous (IVGTT) and oral (OGTT) glucose tolerance tests and hyperglycemic clamp studies with either peripheral or portal glucose infusion was investigated in left-segmentally pancreatectomized dogs with portal ([PPx] n = 7) or systemic ([Tx] n = 7) venous drainage of the remaining pancreas. In Tx dogs, systemic diversion of pancreatic venous effluent was accomplished by gastroduodenal-caval shunt. Data obtained were compared with those in normal control dogs ([NC] n = 7). The loss of pancreatic β-cell mass in PPx dogs decreased insulin responses to peripheral and portal glucose loads. In contrast, Tx dogs showed insulin responses comparable to those of NC dogs to glucose loads via both routes. Against peripheral glucose loads (IVGTT and hyperglycemic clamp with peripheral glucose infusion), PPx and Tx dogs showed deteriorated glucose handling. Against portal glucose loads (OGTT and hyperglycemic clamp with portal glucose infusion), deteriorated glucose handling was observed in Tx dogs, but not in PPx dogs. Deterioration in glycemic regulation against portal glucose loads in left-segmentally pancreatectomized dogs with peripheral insulin delivery but not in pancreatectomized dogs with portal delivery indicates that intraportal hyperglycemia and hyperinsulinemia are essential for promoting hepatic glucose handling.

The effect of systemic venous drainage of the pancreas on insulin sensitivity in dogs.

To assess the metabolic consequences of the diversion of the pancreatic venous drainage to the systemic circulation, the pancreaticoduodenal and gastrosplenic veins were anastomosed to the inferior vena cava in nine normal dogs. This procedure maintained the integrity of the entire pancreas while shunting the hormonal output of the pancreas to the periphery. The metabolic effects were assessed from the sensitivity to insulin during a euglycemic hyperinsulinemic glucose clamp using an insulin infusion of 800 microU/kg per min. The studies were controlled by their duplication in seven dogs identically treated but with the pancreatic veins reanastomosed to the portal vein. No differences in systemic insulin levels or insulin sensitivity before and after surgery were seen under these circumstances. After diversion, however, basal insulin levels rose from 4.5 +/- 1.0 to 11.5 +/- 2.5 microU/ml. Basal glucose metabolic clearance rate (MCR) rose to 3.0 +/- 0.4 from 2.0 +/- 0.3 ml/kg per min. On insulin infusion, maximal stimulation of MCR within the 2-h infusion period was to 15.2 +/- 2.5 ml/kg per min preoperatively and to 7.2 +/- 0.8 ml/kg per min after diversion. Using ratios of MCR-to-insulin concentration as an index of insulin sensitivity, it was demonstrated that this index decreased by at least 50% after diversion. These data imply that portal venous drainage of the pancreas is an important factor in the determination of peripheral insulin sensitivity.

Pancreas transplantation. An initial experience with systemic and portal drainage of pancreatic allografts.

Pancreas transplantation has evolved dramatically since its introduction in 1966. As new centers for transplantation have developed, the evaluation of complications associated with pancreas transplantation has led to advances in surgical technique. Furthermore, surgical alterations of the pancreas resulting from transplantation (systemic release of insulin and denervation) are of unproven consequence on glucose metabolism. Since 1988, the authors have performed 21 transplants (16 combined pancreas/kidney, 3 pancreas alone, which includes 1 retransplantation, 1 pancreas after previous kidney transplant, and 1 "cluster") in 20 patients aged 18 to 49 years; mean, 35 +/- 1 years. Overall patient survival is 95%. Three pancreatic grafts failed within the first year because of technical failure; one additional pancreas was lost to an immunologic event on postoperative day 449, for an overall pancreatic graft survival of 81%. No renal grafts were lost. To evaluate causes of graft failure, demographic data were compared, which included age and sex of the donor and the recipient, operative time, intraoperative blood transfusion, and ischemic time of the graft. No statistically significant differences were found between groups except for ischemic time (11.7 +/- 6.4 hours for the technical success group versus 19.8 +/- 3.7 hours for the technical failure group; p less than 0.05 by unpaired Student's t test). Quadruple immunosuppression was used, which included prednisone, cyclosporine, azathioprine, and antilymphoblast globulin. A mean of 1.2 (range, 0 to 3) rejection episodes per patient occurred. Mean hospital stay was 24 +/- 11 days. Surgical and infectious complications were evaluated by comparing the technical success (TS) group (n = 17) with the technical failure (TF) group. Surgical complications in the TS group revealed a mean of 1.3 episodes per patient, whereas the TF group had 3.7 episodes per patient. The TS also had a reduced incidence of infectious complications compared with the TF (1.7 versus 4.3 episodes per patient). Cytomegalovirus was common in both groups, accounting for 11 infectious episodes, and occurred on a mean postoperative day of 38. Mean postoperative HbA1C levels dropped to 5 +/- 1% from 11 +/- 3%. The authors developed a new technique that incorporates portal drainage of the pancreatic venous effluent in three recipients. Preoperative metabolic studies disclosed a mean fasting glucose of 211 +/- 27 mg/dL and a mean stimulated glucose value of 434 +/- 41 mg/dL for all patients; the mean fasting insulin was 23 +/- 4 microU/mL.(ABSTRACT TRUNCATED AT 400 WORDS)

Surgical alterations of the pancreas and insulin-independent glucose disposal

Systemic drainage of pancreatic venous effluent and denervation of the pancreas that follows pancreatic transplantation has been shown to alter postoperative glucose disposal despite elevated levels of peripheral insulin in response to a glucose challenge. Since an appreciable fraction of postprandial glucose disposal takes place in the absence of insulin (insulin-independent glucose disposal—IIGD), we have investigated potential changes in this aspect of carbohydrate metabolism before and after bladder-drained pancreatic autotransplantation (PAT/B) as well as partial pancreatectomy (PPx). The hyperglycemic clamp protocol with a background infusion of somatostatin was performed on control (PREOP) dogs as well as PAT/B and PPx animals. The rate of glucose disposal ( M Value) during the period of hypoinsulinemia induced by Somatostatin (SST) was measured and reported. Whereas glucose disposal during steady state hyperglycemia was significantly diminished for both PPx and PAT/B in the absence of SST, IIGD was unaltered across all three groups studied. We therefore conclude that surgical alteration of the pancreas results in abnormal glucose disposal during steady state hyperglycemia despite apparently normal to supranormal levels of peripheral insulin, and that alterations in IIGD are not responsible for these differences.

Effects of chronic systemic insulin delivery on insulin action in dogs

The metabolic consequences of the prolonged systemic insulin delivery associated with human pancreas transplantation have not been precisely defined. To determine if systemic insulin delivery in the absence of immunosuppressive agents results in alterations in hepatic or extrahepatic insulin action, three groups of dogs were studied 2 months after either a sham operation or after their pancreatic venous drainage was severed and anastomosed to the inferior vena cava or portal vein (sham, peripheral and portal groups, respectively). The pattern of venous drainage was documented by measuring vena cava and portal insulin concentrations before and after glucose injection. Systemic insulin concentrations were higher (p less than 0.05) in the peripheral group than in the portal group both following a 14-h fast and after intravenous glucose. During a hyperinsulinaemic euglycaemic clamp (1 mU.kg-1.min-1), glucose utilization (measured using [6(3)H]glucose) was slightly lower (p = 0.07) in the peripheral than in the portal group. Hepatic glucose release was equal in all groups. Carbon dioxide incorporation into glucose (an estimate of gluconeogenesis) was higher in the portal than peripheral group in the fasted state but not during insulin infusion. Plasma concentrations and flux rates of fatty acids and amino acids did not differ between groups. We conclude that chronic systemic insulin delivery results in a) systemic but not portal hyperinsulinaemia, b) a minimal impairment in insulin-stimulated glucose uptake, without altering insulin-induced suppression of hepatic glucose release, and c) no effect on fatty acid or amino acid turnover.(ABSTRACT TRUNCATED AT 250 WORDS)