In this paper, we develop a spatio-temporal modeling approach to describe blood and drug flow, as well as drug uptake and elimination, on an approximation of the liver. Extending on previously developed computational approaches, we generate an approximation of a liver, which consists of a portal and hepatic vein vasculature structure, embedded in the surrounding liver tissue. The vasculature is generated via constrained constructive optimization, and then converted to a spatial grid of a selected grid size. Estimates for surrounding upscaled lobule tissue properties are then presented appropriate to the same grid size. Simulation of fluid flow and drug metabolism (hepatic clearance) are completed using discretized forms of the relevant convective-diffusive-reactive partial differential equations for these processes. This results in a single stage, uniformly consistent method to simulate equations for blood and drug flow, as well as drug metabolism, on a 3D structure representative of a liver.

To evaluate safety and efficacy of distal pancreatectomy with en bloc celiac artery resection (DP-CAR) for pancreatic malignancy.

Medical reports of 17 patients who underwent DP-CAR procedure (15 of them with pancreatic malignancy) were retrospectively analyzed. Also we studied 27 publications describing more than 2 cases of DP-CAR.

R0- and R1-resection was performed in 14 (82%) and 3 (18%) patients respectively. Postoperative complications ware observed in 11 (65%) cases. Nine of them were successfully treated. Full pain control was achieved in all patients. There were no any ischemic complications. 16 patients received chemotherapy. 2 (11%) patients died in early postoperative period due to aortic dissection in 10 days and fungal sepsis in 44 days after surgery. Median survival was 20 months. Literature review included 27 articles describing 311 operations. Herewith postoperative complications developed in 43% of cases and 90-day postoperative mortality was 4%. Median survival ranged from 9.3 to 26 months.

DP-CAR is effective and safe procedure in certain patients with locally advanced pancreatic cancer.

An acute increase in portal pressure or reduction in portal inflow has been shown to decrease renal plasma flow (RPF). The aim of the study was to evaluate regional and systemic hemodynamics after acute occlusion of a transjugular intrahepatic portosystemic stent-shunt (TIPSS) and study the effect of the same on plasma endothelin (ET-1) levels in the systemic circulation, renal vein, and hepatic vein. Sixteen patients attending for portography after previous TIPSS placement were studied. The shunt was acutely occluded with an angioplasty balloon for 12 minutes. Changes in portal pressure gradient (PPG), hepatic plasma flow (HPF), RPF, cardiac output (CO), and systemic vascular resistance (SVR) were measured before and after shunt occlusion. Blood was collected from the femoral artery and hepatic and renal veins for ET-1 measurement. At T = 0, SVR correlated with circulating arterial ET-1 level (r = 0.74; P <.05). After shunt occlusion (T = 12 minutes), heart rate, CO, and mean arterial pressure decreased (P <.05), whereas PPG increased (P <.05). RPF decreased from 485 +/- 55 to 282 +/- 47 mL/min (P <.01), whereas HPF increased from 700 +/- 39 to 779 +/- 33 mL/min (P <.001). There was a significant increase in arterial concentration and renal production, and decrease in hepatic production of ET-1. Veno-arterial (V-A) concentration difference in ET-1 level in the renal vein, as well as renal flux of ET-1, increased significantly, whereas hepatic vein V-A concentration difference and hepatic flux of ET-1 decreased significantly. At T = 12 minutes, ET-1 renal output correlated negatively with RPF (r = 0.72; P <.05). Results of this study show that an acute increase in portal pressure and reduction in portal inflow brought about by occlusion of a TIPSS shunt decreases RPF and increases HPF. These hemodynamic changes are accompanied by increases in arterial, renal vein, and hepatic vein ET-1 concentrations, which may possibly mediate the observed findings.

The cardiac and peripheral vascular adjustments to angiotensin II (0.1-0.2 microgram kg-1 min-1 i.v.) during high beta-adrenergic activity by a continuous isoproterenol infusion (0.2-0.3 microgram kg-1 min-1 i.v.) were examined in anaesthetized, atropinized dogs. Hepatic, splenic and left ventricular (LV) volume changes were estimated by an ultrasonic technique, and the blood flow distribution was measured by injecting radioactive microspheres and by electromagnetic flowmetry on the caval veins, the hepatic artery and the portal vein. During isoproterenol infusion, angiotensin II increased the systolic LV pressure by 45 +/- 3 mmHg and the stroke volume by 17 +/- 6%. Concomitantly, the hepatic and splenic blood volumes declined by 29 +/- 4 and 14 +/- 6 ml, respectively, and the LV end-diastolic segment length increased by 3 +/- 1%. The flow through the inferior caval vein increased by 39 +/- 9%, whereas the superior vena caval flow remained unchanged. The hepatic arterial flow more than doubled. Thus, at high inotropy by isoproterenol infusion, angiotensin II relocates blood from the liver and the spleen towards the heart. By activating the Frank-Starling mechanism, cardiac output is increased and conducted through the lower body, especially through the hepatic artery, because of the poor autoregulation of flow through this vessel.

Portal vascular resistance was measured percutaneously in 60 patients with chronic liver disease and in 5 control subjects. The portal vascular resistance (PVR) was calculated, using the following equation, from the portal blood flow (QPV), portal venous pressure (PPV), and hepatic venous pressure (PHV): PVR = (PPV - PHV)/QPV. The portal blood flow was measured using an ultrasonic Doppler duplex system, and the portal venous and hepatic venous pressures were measured using percutaneous transhepatic catheterization and venous catheterization, respectively. The wedged hepatic venous pressure was measured by occluding the hepatic venous branch using a balloon catheter. The portal vascular resistance was 0.25 +/- 0.13 mmHg X ml-1 X min X kg body weight (mean +/- SD, n = 5) in the control group, 0.64 +/- 0.29 mmHg X ml-1 X min X kg body wt (n = 13) in the chronic active hepatitis group, 1.34 +/- 0.79 mmHg X ml-1 X min X kg body wt (n = 30) in the cirrhosis group, and 0.85 +/- 0.69 mmHg X ml-1 X min X kg body wt (n = 13) in the idiopathic portal hypertension group.

Portal blood flow (PBF) can be measured quantitatively using a B-mode combined pulsed Doppler (BCD) system. This system combines a real time B-mode linear type electroscanner and a pulsed Doppler (D-mode) flowmeter. Since both modes are displayed in realtime, Doppler blood flow signals can be retrieved at will from any depth. The blood flow velocity determined by the Doppler spectrogram and the vascular cross-sectional area measured from the B-mode tomographic image enables the quantitative calculation of blood flow volume. Using this system, PBF was measured quantitatively in 88 healthy adults, 54 patients with chronic hepatitis, 65 with cirrhosis of the liver, 27 with primary hepatoma and 12 with idiopathic portal hypertension (IPH). Results of PBF volume measurement were as follows: 889 +/- 284 ml/min (mean +/- S.D.) for healthy adults, 851 +/- 237 ml/min for patients with chronic hepatitis, 870 +/- 289 ml/min for cirrhosis of the liver, 966 +/- 375 ml/min for primary hepatoma and 1,047 +/- 381 ml/min for IPH. These preliminary results demonstrated that this ultrasonic Duplex system is clinically useful to determine the quantitative amount of PBF.

1. The innervated hepatic arterial and portal venous vascular beds of the dog were perfused simultaneously, in situ. Under control conditions, the pressures, blood flows and calculated vascular resistances in these beds were similar to those previously reported in preparations where one bed was perfused alone. 2. The pressure-flow curves in both the hepatic arterial and portal venous vascular beds were almost linear over the pressure ranges 30--200 and 2.5--12.0 mmHg respectively. There was no evidence of pressure-induced autoregulation of flow in either circuit. 3. Increases in hepatic arterial blood flow and perfusion pressure were associated with a linearly related increase in hepatic portal vascular resistance. Occlusion of the hepatic artery caused a mean fall of 21.3% in portal vascular resistance. 4. Increases in hepatic portal blood flow and perfusion pressure were associated with a linearly related incease in hepatic arterial vascular resistance. Occlusion of the hepatic portal vein caused a mean fall of 16.0% in hepatic arterial vascular resistance. 5. Intra-arterial injections of noradrenaline (0.1--50 microgram) caused biphasic changes in hepatic arterial vascular resistance, and a rise in hepatic portal vascular resistance. Both hepatic vascular effects had a significantly shorter latency than any succeeding systemic cardiovascular effects. 6. Intraportal injections of noradrenaline (0.1--50 microgram) caused hepatic portal vasoconstriction, and a biphasic change in the hepatic arterial resistance. Both of these effects had a significantly shorter latency than any succeeding systemic effects. 7. Intra-arterial injections of isoprenaline (0.1--10 microgram) caused dose-dependent hepatic arterial vasodilatation but little change in portal vascular resistance. Intraportal isoprenaline caused little change in portal resistance but elicited dose-dependent hepatic arterial vasodilatation. 8. The time courses of the responses to intra-arterial and intraportal noradrenaline and isoprenaline indicate that the responses of the liver vascular bed which does not receive the direct injection were not due to recirculation of the vasoactive material. 9. It is postulated that vasoactive material injected into one inflow circuit of the liver elicits changes in the vascular resistance of the other inflow circuit by an intrahepatic effect.

1 The hepatic portal vein of the anesthetized dog was cannulated and perfused with blood derived from the cannulated superior mesenteric vein. 2 The portal vein was perfused at constant flow, the hepatic portal venous pressure being monitored continuously together with the inferior vena caval pressure. From these measurements, the hepatic portal venous vascular resistance was calculated. 3 Noradrenaline and adrenaline were injected intraportally in graded doses which caused dose-dependent increases in the hepatic portal vascular resistance. At all doses, adrenaline was significantly (P less than 0.05) more potent than noradrenaline. 4 Intraportal injections of vasopressin caused reductions in calculated hepatic portal venous vascular resistance in most experiments; three effects were dose-dependent. 5 No tachyphylaxis to the effects of noradrenaline, adrenaline or vasopressin was observed. 6 Intraportal injections of angiotensin caused dose-dependent increases in calculated hepatic portal vascular resistance up to 5 mug; therafter larger doses caused smaller increases in portal resistance. 7. Repeated intraportal injections of angiotensin revealed the existence of tachyphylaxis in the hapatic portal vascular bed. 8 Intraportal infusions of anagiotensin caused rises in calculated hepatic portal vascular resistance from which there was almost complete 'escape' despite the continued infusions. Infusions of noradrenaline which caused similar rises in calculated portal vascular resistance did not exhibit equivalent degrees of 'escape'. 9 The development of tachyphylaxisx explains the fact that doses of 10 and 20 mug of angiotensin injected after 5 mug doses produced smaller effects. If a much longer time interval was allowed between injections (30 min), the dose-response curve to angiotensin had a sigmoid shape. 10 These findings are discussed with respect to their possible importance in the functional status of the hepatic portal vascular bed in this species.

Effect of acetylcholine on hepatic circulation was investigated in 33 mongrel dogs. Mean arterial blood pressure, hepatic artery flow, portal vein pressure and portal vein flow were determined after laparotomy under nembutal anesthesia. In order to analyse the complicated responses in hepatic blood flows to 3 mug of acetylcholine hydrochloride, the peripheral resistance of each vascular system was observed in hypotensive dogs, in vascular obliteration dogs and in portal vein shunting dogs. Observation under a hypotensive condition produced by exsanguination revealed that hepatic artery resistance responded to decrease in hepatic artery pressure in different ways depending on whether the systemic blood pressure was above or below 90 mmHg. Experiments in which the hepatic artery or portal vein were obliterated disclosed that there was a certain regularity in the induction of resistance change in the non-injected one of the two hepatic vessels. The result of shunting the portal vein suggested that the complicated change above mentioned would be the expression of the overlapping two sequential responses. Since these results are difficult to explain merely by the direct response of vascular smooth muscle to acetycholine, the possibility that the hypothetical communication between the hepatic artery and portal vein might be a cholinergic system was discussed.