Pancreatic Perfusion Research Articles

Noninvasive examinations for localization of insulinoma

To investigate the value of the noninvasive examinations for localization of insulinoma. The clinical materials of 88 cases of insulinoma treated in Peking Union Medical College Hospital between January 2005 and November 2008 were analyzed retrospectively. There were 40 males and 48 females aged from 15 to 74 years old (averaged, 46.5 years old). The positive rates for localization were 19.3% (17/88), 52.4% (11/21), 95.5% (64/67), 1/6, 30.0% (6/20), 83.9% (26/31), 8/8 and 5/5 respectively in transabdominal ultrasound, enhanced CT, multislice spiral CT pancreatic perfusion, MRI, somatostatin receptor scintigraphy, endoscopic ultrasound, laparoscopic ultrasound and intraoperative ultrasound. Thirty-one multiple tumors in 8 patients were resected. The positive rates of locating the multiple insulinomas of multislice spiral CT pancreatic perfusion and Intraoperative Ultrasound were 48.4% (15/31) and 100% (14/14) respectively. The locating diagnosis of insulinoma has came to noninvasive examination era. Multislice spiral CT pancreatic perfusion is the first choice for localization. Intraoperative ultrasound might play an important role in locating tumors for patients with multiple insulinomas.

Correlation between Pancreatic Microcirculation and Type 2 Diabetes in Patients with Coronary Artery Disease: Dynamic Contrast-enhanced MR Imaging

To evaluate pancreatic perfusion by using dynamic contrast material-enhanced (DCE) magnetic resonance (MR) imaging with pharmacokinetic modeling in coronary artery disease (CAD) patients with and those without type 2 diabetes to determine which perfusion parameter alterations might be associated with type 2 diabetes. This prospective study was approved by the responsible institutional review board. Written informed consent was obtained from all patients. All patients studied had CAD documented at conventional angiography. DCE MR with a two-dimensional T1-weighted fast low-angle shot sequence in oblique axial planes was used to assess pancreatic microcirculation in patients with and those without type 2 diabetes (age +/- standard deviation, 60.8 years +/- 11.2 and 61.8 years +/- 11.2, respectively; 20 men and five women in each group). Microcirculatory quantitative parameters, including volume transfer constant (K(trans), in min(-1)), extravascular extracellular space volume per unit volume of tissue (v(e)), and plasma volume per unit volume of tissue (v(p)) were compared between groups by using independent-sample t tests. Patients with diabetes had a significantly higher K(trans) (0.977 vs 0.696, P = .031) and a lower v(p) (0.057 vs 0.084, P = .005) compared with patients without diabetes. A borderline difference in v(e) was found between the diabetes and nondiabetes groups (0.141 vs 0.103, P = .05). Among the 25 patients with diabetes, those who had the condition for more than 10 years (n = 11) had significantly higher K(trans) and v(e) than did those who had diabetes for less than 10 years (n = 14) (1.145 vs 0.783 and 0.174 vs 0.108; P = .04 and .02, respectively). DCE MR imaging demonstrated increased endothelial permeability and decreased plasma volume in the pancreas in CAD patients with type 2 diabetes; patients with a history of diabetes for more than 10 years showed further increase in endothelial permeability.

Measurement of canine pancreatic perfusion using dynamic computed tomography: Influence of input–output vessels on deconvolution and maximum slope methods

We investigated whether the prerequisite of the maximum slope and deconvolution methods are satisfied in pancreatic perfusion CT and whether the measured parameters between these algorithms are correlated. We examined nine beagles injected with iohexol (200 mgI kg(-1)) at 5.0 ml s(-1). The abdominal aorta and splenic and celiac arteries were selected as the input arteries and the splenic vein, the output veins. For the maximum slope method, we determined the arterial contrast volume of each artery by measuring the area under the curve (AUC) and compared the peak enhancement time in the pancreas with the contrast appearance time in the splenic vein. For the deconvolution method, the artery-to-vein collection rate of contrast medium was calculated. We calculated the pancreatic tissue blood flow (TBF), tissue blood volume (TBV), and mean transit time (MTT) using both algorithms and investigated their correlation based on vessel selection. The artery AUC significantly decreased as it neared the pancreas (P<0.01). In all cases, the peak time of the pancreas (11.5±1.6) was shorter than the appearance time (14.1±1.6) in the splenic vein. The splenic artery-vein combination exhibited the highest collection rate (91.1%) and was the only combination that was significantly correlated between TBF, TBV, and MTT in both algorithms. Selection of a vessel nearest to the pancreas is considered as a more appropriate prerequisite. Therefore, vessel selection is important in comparison of the semi-quantitative parameters obtained by different algorithms.

Pancreatic perfusion of healthy individuals and type 1 diabetic patients as assessed by magnetic resonance perfusion imaging

Loss of pancreatic beta cell mass and function leads to the development of diabetes mellitus. Currently there is no technical way to non-invasively image islet function and mass. Murine models suggest that islets are highly vascularised organs that make a significant contribution to the total pancreatic blood flow. The current study was undertaken to test with arterial spin labelling (ASL) magnetic resonance imaging if islet mass and/or stimulation of human pancreatic islets by hyperglycaemia can differentially increase whole-pancreas perfusion, thereby distinguishing non-diabetic from type 1 diabetic patients. We assessed pancreatic blood flow using ASL at baseline, during a hyperglycaemia clamp study (glucose at 11 mmol/l) and during recovery to euglycaemia. Seventeen healthy volunteers and seven type 1 diabetic patients were studied. In healthy volunteers we observed no change in pancreatic blood flow during the three phases of the study. A trend for an increase in blood flow was observed in the two control tissues, the liver and kidney. Similarly, there was no significant difference in blood flow during the three stages (baseline, hyperglycaemia and recovery) in diabetic patients and there was no significant difference observed between diabetic patients and normal volunteers. Our data suggest that in humans neither increased demand nor islet mass has a substantial influence on pancreatic perfusion. It is possible, however, that the current state-of-the art imaging technology employed in this study might not be sensitive enough to distinguish between a true effect and noise. ClinicalTrials.gov NCT00280085.

DCE‐MRI in experimental chronic pancreatitis

To assess pancreatic perfusion in experimental chronic pancreatitis (CP) by dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI). DCE MRI on a 1.5 T MR scanner was performed on 21 piglets with the ligation of pancreatic duct. They were divided into four groups based on pathology, including seven normal pigs and seven, three and four piglets with grade I, II and III CP, respectively. The signal intensity measured in the pancreatic body on DCE MRI was plotted against time to create a signal intensity-time (SI-T) curve for each piglet. The steepest slope (SS), time-to-peak (TTP) and peak enhancement ratio (PER) of the SI-T curve were noted. In the four groups, on the SI-T curve derived from DCE MRI, the SS was, respectively, 10.88 +/- 1.20, 10.59 +/- 1.02, 6.67 +/- 1.31 and 5.48 +/- 1.97%/s (F = 20.509, p = 0.000) from normal piglets to piglets with grade III CP. The TTP was 13.82 +/- 3.09, 12.31 +/- 5.52, 20.55 +/- 3.79 and 37.26 +/- 14.56 s (F = 10.681, p = 0.000) and the PER was 62.95 +/- 20.20, 60.44 +/- 20.00, 46.33 +/- 22.70 and 67.65 +/- 32.66% (F = 0.529, p = 0.668), respectively. The SS (r = -0.719, p = 0.000) and TTP (r = 0.538, p = 0.012) of the SI-T curve was correlated to the severity of CP, respectively. DCE MRI has a potential to diagnose moderate to advanced CP. The SS and TTP of the SI-T curve were correlated to the severity of CP.

Deletion of Glutamate Dehydrogenase in ß-Cells Abolishes Part of the Insulin Secretory Response Not Required for Glucose Homeostasis

Insulin exocytosis is regulated in pancreatic ss-cells by a cascade of intracellular signals translating glucose levels into corresponding secretory responses. The mitochondrial enzyme glutamate dehydrogenase (GDH) is regarded as a major player in this process, although its abrogation has not been tested yet in animal models. Here, we generated transgenic mice, named betaGlud1(-/-), with ss-cell-specific GDH deletion. Our results show that GDH plays an essential role in the full development of the insulin secretory response. In situ pancreatic perfusion revealed that glucose-stimulated insulin secretion was reduced by 37% in betaGlud1(-/-). Furthermore, isolated islets with either constitutive or acute adenovirus-mediated knock-out of GDH showed a 49 and 38% reduction in glucose-induced insulin release, respectively. Adenovirus-mediated re-expression of GDH in betaGlud1(-/-) islets fully restored glucose-induced insulin release. Thus, GDH appears to account for about 40% of glucose-stimulated insulin secretion and to lack redundant mechanisms. In betaGlud1(-/-) mice, the reduced secretory capacity resulted in lower plasma insulin levels in response to both feeding and glucose load, while body weight gain was preserved. The results demonstrate that GDH is essential for the full development of the secretory response in beta-cells. However, maximal secretory capacity is not required for maintenance of glucose homeostasis in normo-caloric conditions.

Feasibility of Measurement of Pancreatic Perfusion Parameters with Single-Compartment Kinetic Model Applied to Dynamic Contrast-enhanced CT Images

To examine the feasibility of measuring pancreatic perfusion parameters by using a single-compartment kinetic model applied to contrast material-enhanced computed tomographic (CT) images. This study received institutional review board approval and was HIPAA compliant. Informed consent was waived. Eight subjects (four men, four women; median age, 40 years; range, 35-57 years), all potential renal donors with no pancreatic pathologic abnormalities, underwent abdominal CT imaging, which resulted in 30 10-mm-thick sections obtained at a single level. Imaging was a direct result of bolus timing employed for standard renal donor protocol; no additional imaging beyond what was clinically warranted was performed. Images were obtained every 3 seconds; scanning was initiated at the onset of contrast material administration. Region-of-interest measurements were obtained for the pancreatic body and the aorta to generate time-enhancement curves (TECs). A one-compartment model was applied by using the aortic and pancreatic TECs as the input and output functions, respectively. Pancreatic volumetric blood flow F(V), volume of distribution V(D), and blood transit time tau were determined. Modeled pancreatic TECs were generated and were compared with actual TECs for wellness of fit. Pancreatic F(V) values from the single-compartment model ranged from 0.961 to 6.405 min(-1) (mean, 3.560 min(-1) +/- 1.900 [standard deviation]). Volume of distribution V(D) ranged from 1.491 to 3.080 (mean, 2.383 +/- 0.638), while values of tau ranged from -3.090 to 6.436 seconds (mean, 0.481 second +/- 3.000). Modeled pancreatic TECs closely matched true pancreatic TECs for each subject, with R(2) values ranging from 0.840 to 0.959. A simple one-compartment kinetic model can be applied to contrast-enhanced images of normal pancreas to yield accurate pancreatic TECs, which attest to the perfusion parameters obtained. In addition to yielding volumetric blood flow similar to that of other models of tissue perfusion, two additional pancreatic perfusion parameters can be obtained. http://radiology.rsnajnls.org/cgi/content/full/2492080026/DC1.

Insulin secretion is highly sensitive to desorption of plasma membrane cholesterol

Cholesterol-rich clusters of SNARE (soluble NSF attachment protein receptor) proteins have been implicated as being important for exocytosis. Here we demonstrate the significance of cholesterol for normal biphasic insulin secretion in mouse beta cells by removal of cholesterol from the plasma membrane using methyl-beta-cyclodextrin (MBCD). Maximal inhibition of insulin secretion in static incubations was achieved using 0.1 mM MBCD. In in situ pancreatic perfusion measurements, both first and second phase insulin secretions were reduced by approximately 50% (P<0.05). This was accompanied by a reduced number of docked large dense core vesicles (LDCVs) (approximately 40%; P<0.01) and a reduced exocytotic response (>50%; P<0.01). Further, subcellular fractionations demonstrated movement of the synaptosomal protein of 25 kDa (SNAP-25) from the plasma membrane to the cytosol after MBCD treatment. The inhibitory actions of MBCD were counteracted by subsequent addition of cholesterol. We hypothesize that desorption of cholesterol leads to the disturbance of a basic exocytotic mechanism partly due to migration of SNAP-25, and we conclude that insulin secretion is highly sensitive to changes in plasma membrane cholesterol.

DIAGNOSIS OF ACUTE NECROTIZING PANCREATITIS BY PERFUSION CT IN THE ERALY PHASE OF ACUTE PANCREATITIS

Perfusion imaging by MDCT (perfusion CT) is a new modality to measure tissue perfusion of the pancreas in acute pancreatitis.1 We examined whether perfusion CT in the early phase of acute pancreatitis can detect ischemic area in the pancreas leading to pancreatic necrosis. We investigated pancreatic perfusion measurement using MDCT in 12 patients with acute pancreatitis within the first 72 hr after the onset and two weeks after the admission. Perfusion, peak enhancement intensity and blood volume was significantly lower in poorly perfused area of the pancreas in acute necrotizing pancreatitis (ANP) than those in acute edematous pancreatitis (AEP) and those in perfused area of the pancreas in ANP on admission (Table 1). Two weeks later, perfusion in AEP and perfused area of ANP was recovered to almost normal range, whereas perfusion in poorly perfused area (ischemic area) of the pancreas in ANP was decreased (Fig. 1). Pancreatic necrosis was confirmed by operation or follow-up CT examination in accordance with the ischemic region of the pancreas detected by perfusion CT. Perfusion CT in the early phase of acute pancreatitis is useful for detection of ischemic change in the pancreas leading to pancreatic necrosis.TABLE 1: Parameters of Perfusion CT in Cases with Acute PancreatitisFIGURE 1: Changes in perfusion parameters of the pancreas: A, perfusion; B, blood volume. AEP: acute edematous pancreatitis ANP: acute necrotizing pancreatitis.

MR perfusion weighted imaging of the swines with experimental chronic pancreatitis

Objective To characterize pancreatic perfusion in swines with experimental chronic pancreatitis(CP)by dynamic contrast-enhanced MRI and to correlate it with the severity of CP.Methods Twenty-two swines were randomly selected and made CP by ligation of main pancreatic duct.Six healthy swines served as control.MR perfusion study with dynamic contrast-enhanced MRl was carried out on the swines under anesthesia.The animals were euthanized after MR perfusion exam.The swines were divided into 4 groups according to the histological results of pancreas:normal group,group of CP of grade 1,group of CP of grade 2,and group of CP of grade 3.The maximum perfusion slope rate,the time-to-peak value and the maximum enhancement rate was compared between the groups using variance analysis,and the relationship between each perfusion parameters and severity of CP was made by correlative analysis.Results Twenty-one swines underwent MR perfusion study,including 7 swines in normal group,7 in group of grade 1 CP,3 in group of grade 2 CP,and 4 in group of grade 3 CP.On signal intensity time curve(SI-T)derived from MR perfusion weighted imaging,the m~imum slope rate was(10.88±1.20)%,(10.59±1.02)%,(6.67±1.31)%,and(5.48±1.97)%for normal swines,swines with grade 1 CP,swines with grade 2 CP and swines with grade 3 CP,respectively(F=20.51,P＜0.05).The time-to-peak value was(13.82±3.09)s,(12.31±5.52)s,(20.55±3.79)s and(37.26±14.56)s respectively(F=10.68,P＜0.05).The maximal signal enhancement rate was(62.95±20.20)%,(60.44±20.00)%,(46.33±22.70)%,and(67.65±32.66)%,respectively(F=0.53,P＞0.05).The highest slope value(r=-0.72,P＜0.05)and the time-to-peak(r=0.54,P＜0.05)of the SI-T curve were correlated to the severity of CP,respectively.However there was no linear correlation between the maximal signal enhancement rate and the severity of CP.Conclusion MR perfasion weighted imaging has a potential to diagnose and to grade experimental chronic pancreatitis. Key words: Pancreatitis,chronic; Magnetic resonance imaging; Perfusion; Swine

Pancreatic Perfusion: Noninvasive Quantitative Assessment with Dynamic Contrast-enhanced MR Imaging without and with Secretin Stimulation in Healthy Volunteers—Initial Results

To prospectively quantify pancreatic regional perfusion with dynamic contrast material-enhanced magnetic resonance (MR) imaging by using a one-compartment model and to assess perfusion changes during secretin stimulation in healthy volunteers. The study had institutional review board approval, and written informed consent was obtained. Ten healthy volunteers (five men, five women; mean age, 24.7 years +/- 1.9 [standard deviation]; range, 22-29 years) underwent MR imaging pancreatic perfusion studies performed twice without secretin and twice during secretin stimulation. Dynamic contrast-enhanced MR imaging consisted of saturation-recovery T1-weighted turbo-field-echo imaging with peripheral pulse triggering and respiratory tracking. A dose of 0.05 mmol gadodiamide per kilogram of body weight was injected at a rate of 3.5 mL/sec. Regional perfusion parameters were fitted with a one-compartment model. The analysis of variance test for repeated measurements was used to assess differences in pancreatic perfusion without and that with secretin administration. Significant differences in perfusion parameters between the three pancreatic regions were observed (P < .05). During secretin stimulation, a significant difference was observed only between the body and the tail of the pancreas (P = .02). A significant increase (P = .003) in pancreatic perfusion was observed after secretin administration. Mean pancreatic perfusion was 184 mL/min/100 g of tissue +/- 71, 207 mL/min/100 g +/- 77, and 230 mL/min/100 g +/- 87 without secretin and 342 mL/min/100 g +/- 154, 338 mL/min/100 g +/- 156, and 373 mL/min/100 g +/- 176 after secretin stimulation in the head, body, and tail of the pancreas, respectively. Intraindividual variability was 21% without secretin stimulation and 46% with secretin stimulation. Dynamic contrast-enhanced MR imaging enables noninvasive quantification of regional pancreatic perfusion in resting conditions and demonstrates the increase in pancreatic perfusion during secretin stimulation in healthy subjects.

Radiological contrast media and pancreatic blood perfusion in anesthetized rats

Radiological contrast media (CM) have been suggested to be able to impair pancreatic microcirculation. To evaluate the effects of an iso-osmolar (iodixanol, 290 mOsm/kg H2O) and a low-osmolar (iopromide, 660 mOsm/kg H2O) CM on total pancreatic and islet blood perfusion. Thiobutabarbital-anesthetized rats were injected with iodine equivalent doses (600 mg I/kg body weight) of iodixanol or iopromide. Saline or low-osmolar mannitol (660 mOsm/kg H2O) solutions served as control substances. Blood perfusion measurements were then carried out with a microsphere technique. Iso-osmolar iodixanol had no effects on blood perfusion. Low-osmolar iopromide increased total pancreatic blood perfusion, whereas islet blood perfusion was unchanged. No differences were seen when mannitol solutions were given. Neither an iso-osmolar nor a low-osmolar CM affected pancreatic islet blood perfusion, whereas the low-osmolar CM increased total pancreatic blood perfusion. The absence of hemodynamic effect of low-osmolar mannitol suggests that the hyperosmolality per se of iopromide versus iodixanol does not induce the hemodynamic effect. The consequences of the effect of iopromide for pancreatic function remain to be established.

Hemodynamic effect of iopromide in pancreas-duodenum transplanted rats

Radiological contrast media (CM) have been suggested to be able to impair pancreatic microcirculation, especially in acute pancreatitis. To evaluate the effects of the low-osmolar CM iopromide on total pancreatic and especially islet blood perfusion after whole pancreas transplantation. Rats receiving a pancreas-duodenum transplantation 2 days earlier, i.e., with graft pancreatitis, were injected with iopromide. Blood perfusion measurements were then made with a microsphere technique. The graft blood perfusion was decreased in control rats when compared to the endogenous pancreas. Administration of iopromide increased both total pancreatic and islet blood perfusion in the grafted pancreas, but not in the endogenous gland. No effects on blood perfusion to either the native or transplanted duodenum were seen after iopromide administration. Iopromide increases the blood perfusion of a whole pancreas transplant 2 days after implantation, i.e., when graft pancreatitis is present. The consequences of this CM-induced hyperperfusion for graft pancreatic function remain to be established.Key words: Intravascular contrast media; islet blood perfusion; graft pancreatitis;pancreas transplantation; pancreatic blood perfusion

ISCHEMIC ACUTE PANCREATITIS

Background: Acute pancreatitis (AP) can be caused by various triggers. Besides alcohol excess and gallstones, pancreatic ischemia can cause AP. Although this is poorly defined clinically or radiologically as an independent entity, it should be considered when anamnestic risk factors are present and no other obvious reasons can be defined. Aim of this study was to define ischemic AP in terms of pathophysiological, radiological and clinical conditions regarding the history of 7 consecutive patients. Methods: Seven patients suffered from acute pancreatitis caused by mesenteric hypoperfusion of different origin. Course, severity and outcome of the disease as well as diagnostic and therapeutic measures were evaluated with a special focus on the differentiation between acute pancreatitis and elevated pancreatic enzyme levels, which can often be observed in ICU patients without further clinical complications. Results: Three causes of acute ischemia-induced pancreatitis were observed: hemorrhage or hypotension (3 patients), mesenteric macrovessel occlusion (3 patients) and posttransplantation pancreatitis (1 patient). Therapy of the patients was conservative in 2 patients, operative with surgical hemostasis and drainage (4 patients) and explantation of a transplanted pancreas (1 patient), respectively. Four of the patients died within 18 days after the onset of AP, indicating a severe course of AP with major systemic complications; 2 patients recovered completely, the transplant patient lost the pancreas graft after 5 days without further complications. Conclusions: Ischemia is an important etiology of acute pancreatitis. Different causes of ischemia can lead to a hypoperfusion of the pancreas with a consecutive induction of an inflammatory response. Diagnostic and therapeutic procedures are similar to those performed in acute pancreatitis of other etiology, causal therapy includes restoration of pancreatic perfusion, if possible. Severity of the disease can range from moderate edematous affections up to severe courses with lethal outcome. However, in the reported patients mortality was high, indicating that ischemia of the pancreas, when present at the onset of the disease, tends to lead to a severe, often irreversible organ damage with early and fatal systemic complications.

Dynamic computed tomographic quantitation of hepatic perfusion in dogs with and without portal vascular anomalies

To compare hepatic, pancreatic, and gastric perfusion on dynamic computed tomography (CT) scans of clinically normal dogs with those of dogs with portal vascular anomalies. Dynamic computed tomography (CT) scans of 10 clinically normal dogs and 21 dogs with portal vascular anomalies. Retrospective analysis of dynamic CT scans. Hepatic arterial perfusion, hepatic portal perfusion, total hepatic perfusion, hepatic perfusion index, gastric perfusion, and pancreatic perfusion were calculated from time attenuation curves. Mean +/- hepatic arterial perfusion was significantly higher in affected dogs (0.57 +/- 0.27 mL/min x mL(-1)) than in clinically normal dogs (0.23 +/- 0.11 mL/min x mL(-1)), and hepatic portal perfusion was significantly lower in affected dogs (0.52 +/- 0.47 mL/min x mL(-1)) than in clinically normal dogs (1.08 +/- 0.45 mL/min x mL(-1)). This was reflected in the hepatic perfusion index, which was significantly higher in affected dogs (0.59 +/- 0.34), compared with clinically normal dogs (0.19 +/- 0.07). Gastric perfusion was significantly higher in dogs with portal vascular anomalies (0.72 +/- 0.44 mL/min x mL(-1)) than in clinically normal dogs (0.41 +/- 0.21 mL/min x mL(-1)), but total hepatic perfusion and pancreatic perfusion were not significantly different. Among subgroups, dogs with congenital intrahepatic portosystemic shunts and dogs with arterioportal fistulae had higher hepatic arterial perfusion than did clinically normal dogs. Dogs with congenital intrahepatic portosystemic shunts also had an increase in gastric perfusion and hepatic perfusion index. Hepatic perfusion variables measured on CT scans revealed differences in hemodynamics between clinically normal dogs and those with portal vascular anomalies.

Comparison of Intrahepatic and Pancreatic Perfusion on Fusion Images Using a Combined SPECT/CT System and Assessment of Efficacy of Combined Continuous Arterial Infusion and Systemic Chemotherapy in Advanced Pancreatic Carcinoma

The purpose of this study was to compare intrahepatic and pancreatic perfusion on fusion images using a combined single-photon emission computed tomography (SPECT)/CT system and to evaluate the efficacy of combined continuous transcatheter arterial infusion (CTAI) and systemic chemotherapy in the treatment of advanced pancreatic carcinoma. CTAI was performed in 33 patients (22 men, 11 women; age range, 35-77 years; mean age, 60 years) with stage IV pancreatic cancer with liver metastasis. The reservoir was transcutaneously implanted with the help of angiography. The systemic administration of gemcitabine was combined with the infusion of 5-fluorouracil via the reservoir. In all patients we obtained fusion images using a combined SPECT/CT system. Pancreatic perfusion on fusion images was classified as perfusion presence or as perfusion absent in the pancreatic cancer. Using WHO criteria we recorded the tumor response after 3 months on multislice helical CT scans. Treatment effects were evaluated based on the pancreatic cancer, liver metastasis, and factors such as intrahepatic and pancreatic perfusion on fusion images. For statistical analysis we used the chi-square test; survival was evaluated by the Kaplan Meier method (log-rank test). On fusion images, pancreatic and intrahepatic perfusion was recorded as hot spot and as homogeneous distribution, respectively, in 18 patients (55%) and as cold spot and heterogeneous distribution, respectively, in 15 (45%). Patients with hot spot in the pancreatic tumor and homogeneous distribution in the liver manifested better treatment results (p < 0.05 and p < 0.01, respectively). Patients with hot spot both in the pancreatic cancer and in the liver survived longer than those with cold spot in the pancreatic cancer and heterogeneous distribution in the liver (median +/- SD, 16.0 +/- 3.7 vs. 8.0 +/- 1.4 months; p < 0.05). We conclude that in patients with advanced pancreatic cancer, CTAI with systemic chemotherapy appeared to be effective and may prolong their survival. The development of a reservoir port system allowing for the homogeneous distribution of anticancer drugs is necessary to improve the prognosis of patients with advanced pancreatic cancer.

식이 지방이 췌장 90%를 제거한 당뇨 흰쥐의 인슐린 분비능과 췌장 베타세포의 양에 미치는 영향

The prevalence of diabetes has increased to 8% of population. Unlike type 2 diabetes in the western countries, Korean diabetic patients are nonobese and have low serum insulin levels. As the increased prevalence of diabetes and the peculiar characteristics may be related to dietary fat contents, we determined their effects on insulin resistance, insulin secretion and pancreatic β-cell mass in 90% pancreatectomized (Px) diabetic rats in the present study. The rats were provided with low fat diet (LF, 10 energy% fat), moderate fat diet (MF, 25 energy% fat) and high fat diet (HF, 40 energy% fat) for 6 months. HF increased body weight and epidydimal fat pads parallel with increased food intake compared to LF and MF. Fasting serum glucose and insulin levels and homeostasis model assessment of insulin resistance were higher in HF, compared to LF and MF, indicating that HF increased insulin resistance. Rats fed LF and MF diets reduced insulin resistance, but only rats fed MF improved pancreatic β-cell mass and insulin secretion capacity, measured by hyperglycemic clamp and in situ pancreatic perfusion. LF had low insulin secretion capacity and pancreatic β-cell mass, indicating the increased possibility of diabetic prevalence and progression. MF increased β-cell mass by stimulating β-cell proliferation and neogenesis and reducing β-cell apoptosis. In conclusion, MF is effective for the prevention of prevalence and progression of diabetes.

Arginase Increases Total Pancreatic and Islet Blood Flow in Anaesthetized Mice

Background. Previous studies have demonstrated that the high basal pancreatic islet blood perfusion is crucially dependent on nitric oxide formation. Arginase can interfere with the formation of nitric oxide by limiting substrate availability. The aim of the present study was to evaluate the influence of arginase on islet blood perfusion in anasthetized mice.Methods. The blood perfusion of the pancreatic islets was measured with a microsphere technique in anaesthetized NMRI mice after administration of arginase.Results: Arginase administration increased both total pancreatic and islet blood flow to the same degree. Also adrenal blood flow was increased, whereas other organ blood flow values were unaffected.Conclusion. Arginase induces a paradoxical increase in pancreatic and islet blood flow, the reasons for which are still unknown.

Alkali pH directly activates ATP-sensitive K + channels and inhibits insulin secretion in β-cells

Glucose stimulation of pancreatic β-cells is reported to lead to sustained alkalization, while extracellular application of weak bases is reported to inhibit electrical activity and decrease insulin secretion. We hypothesize that β-cell K ATP channel activity is modulated by alkaline pH. Using the excised patch–clamp technique, we demonstrate a direct stimulatory action of alkali pH on recombinant SUR1/Kir6.2 channels due to increased open probability. Bath application of alkali pH similarly activates native islet β-cell K ATP channels, leading to an inhibition of action potentials, and hyperpolarization of membrane potential. In situ pancreatic perfusion confirms that these cellular effects of alkali pH are observable at a functional level, resulting in decreases in both phase 1 and phase 2 glucose-stimulated insulin secretion. Our data are the first to report a stimulatory effect of a range of alkali pH on K ATP channel activity and link this to downstream effects on islet β-cell function.

Perfusion Measurement in Acute Pancreatitis Using Dynamic Perfusion MDCT

Our objective was to determine whether MDCT with perfusion imaging could help in assessing the severity of acute pancreatitis in the initial phase of the disease. One hundred six patients with abdominal pain were prospectively enrolled in this study. Patients were separated into two groups: P1 (severe) and P2 (mild) acute pancreatitis. Mean perfusion value was 24.8 mL/100 mL/min in the P1 group and 50.5 mL/100 mL/min in the P2 group (p = 0.0016, significant). Our preliminary data suggest that pancreatic perfusion measurement using MDCT with perfusion imaging could help in assessing the severity of acute pancreatitis.