Hideki Nishiwaki

Renal function in experimentally induced acute pancreatitis in dogs: How it is affected by the nephrotoxic substance in pancreatic exudate from ascitic fluid

Renal failure occurring in dogs during experimental acute pancreatitis and the effect on renal function of intravenous injections of ascitic fluid which accumulated during the acute pancreatitis were studied. Five hours after the induction of acute pancreatitis, the accumulation of 200 to 400 ml of ascitic fluid, and an elevation in hematocrit as well as a decreased mean arterial pressure were observed, which suggested hypovolemia due to plasma loss. At the same time, the renal blood flow, glomerular filtration rate, and urinary output decreased significantly. Hypovolemia was observed to be the main cause of renal failure in accordance with previous reports. When the sterile ascitic fluid was injected into healthy dogs, temporary hypotension was observed without changes in the hematocrit. However, the renal blood flow, glomerular filtration rate and urinary output decreased, together with an elevation in renal vascular resistance, even after the hypotension had returned to normal. This study shows that renal failure associated with acute pancreatitis occurred mainly as a direct result of hypovolemia but also that the sterile ascitic fluid contained nephrotoxic substances which were suspected to be unrelated to vasoactive substances or protease. Their removal is therefore necessary for the treatment and prevention of renal failure complicating acute pancreatitis.

Malignant T-cell lymphoma of the pancreas.

A case of malignant T-cell lymphoma of the pancreas is presented. Previously reported histological data confirming this disease are reviewed to elucidate features that may suggest this disease and how to differentiate between T- and B-cell lymphoma of the pancreas.

Renal Microcirculation in Experimental Acute Pancreatitis of Dogs

In order to understand the mechanism of acute renal failure frequently observed in severe acute pancreatitis, renal microcirculation and renal hemodynamics were investigated during experimental acute pancreatitis in dogs induced by autologous bile and trypsin mixture into the pancreatic duct. Renal tissue blood flow (hydrogen gas clearance method), renal arterial blood flow, and cardiac output (transonic blood flow meter) were each measured for 5 h after induction of pancreatitis. The effect on renal hemodynamics of a new synthesized protease inhibitor--E-3123; 4-(2-succinimidoethylthio)phenyl-4-quanidinobenzoate methane sulfonate--intravenously infused at the rate of 3 mg/kg/h was also investigated. The mean blood pressure and pulse pressure decreased after induction of pancreatitis. Renal microcirculation and renal artery blood flow decreased during the experiment. However, in dogs with treated by E-3123, renal microcirculation was preserved during the first hour of the experiment and decreased gradually afterward, but it was significantly higher than that of the dogs without E-3123 during 3-5 h. The mean blood pressure and pulse pressure were preserved nearly at preoperative levels during the experimental period. We concluded that renal microcirculation decreased concomitantly with a deterioration of acute pancreatitis, and that the new pancreatic protease inhibitor E-3123 may have some beneficial effect to improve renal hemodynamics in the early period of acute pancreatitis.

A clinical evaluation of various tumor markers for the diagnosis of pancreatic cancer

SummaryMany substances that are widely used as tumor markers for detecting pancreatic cancer are discussed. Some are good indicators, but some are not. Among them, CA 19–9 and SPan-1 have higher sensitivity and specificity for diagnosis of pancreatic cancer. However, these markers are neither tumor-specific nor pancreatic-cancer-specific. Accurate understanding of the measurement of serum tumor markers makes it possible for them to be useful adjunctive tools for detecting pancreatic cancer, even in small cancers, and for monitoring patients after treatment.

Serial histologic study of the development, progression, and healing of acute pancreatitis in the rat

This study was undertaken to investigate serially the development, progression, and healing of acute pancreatitis which was induced in rats by the closed duodenal loop technique. Edematous changes appeared within 2 to 4 h. Pancreatic blood flow increased at 1 h and tended to decrease after 3 h. After injection of fesin into the loop, fesin appeared in the periacinar space and acinar cells after 4 h. Electron microscopy showed that partial destruction of the plasma membrane occurred and serum amylase increased considerably at the same time, suggesting that the initial inflammatory changes caused the release of pancreatic enzymes at −4 h. After elimination of the causal factors, edematous pancreatitis healed completely but hemorrhagic acute pancreatitis was not completely healed 6 months later.

Effect of a new cholecystokinin receptor antagonist (KSG 504) on the early stage of the healing process in acute pancreatitis induced in rats by the closed duodenal loop technique

Creation of a closed duodenal loop produced edematous acute pancreatitis within 6 h and hemorrhagic acute pancreatitis within 12 h in male Sprague-Dawley rats. The pancreatitis thus established tended to improve after releasing the loop. We investigated the effect of a new cholecystokinin receptor antagonist, KSG 504, on the healing process in edematous and hemorrhagic acute pancreatitis after releasing the loop. Serum amylase and lipase levels in the control group decreased gradually after releasing the loop, but the reductions were not significant. In both the group treated with KSG 504 intravenously and the group treated subcutaneously, serum amylase and lipase levels decreased markedly upon release of the loop in edematous acute pancreatitis. Furthermore, the histologic changes in edematous acute pancreatitis improved more rapidly than in the control group. However, no such biochemical or histologic evidence of improvement was observed in hemorrhagic acute pancreatitis. The new cholecystokinin receptor antagonist, KSG 504, displayed a therapeutic effect in edematous acute pancreatitis but not in hemorrhagic acute pancreatitis. These findings suggest that endogenous cholecystokinin release induced by the closed duodenal loop may have a contributory role in the development of edematous acute pancreatitis but not of hemorrhagic acute pancreatitis.

Various tumor markers for small pancreatic cancer with special reference to the present status of pancreatic cancer in Japan and our experience over the past 2 years.

Various tumor markers for detection of small pancreatic cancer <4.0 cm of diameter were evaluated and our recent 2 year experience is presented. Even in T, cancer, 62.5% of the patients (N = 24) had elevated serum CA 19–9 and 56.5% of the patients also had elevated serum Span-1. However, that of other markers was less than 30% except for CA 50 (60%). In T1 cancer, the highest sensitivity was observed for Span-1 (79.6%, N = 54) and that of Ca 19–9 (N = 54) was also high (77.7%). That of other markers was less than 50%. The combination assay of CA 19–9 and Span-1 in T, cancer increased sensitivity from a single assay of 62.5% and 56.5%, respectively, to 70%. In T, cancer, the sensitivity of the combination was 97.1%. All of our cases showed positive results using serum Span-1 and/or CA 19–9 before confirming the diagnosis with imaging procedures. By applying measurements accurately, the test is a very useful adjunct to the diagnosis of small pancreatic cancer and therefore improves its prognosis.

Effect of a synthetic protease inhibitor (Fut-175) on coagulation abnormalities during experimental acute pancreatitis in dogs

SummaryThe coagulation disturbance observed during severe acute pancreatitis before and after the infusion of a new synthetic low molecular weight protease inhibitor (Fut-175) was compared. The coagulofibrinolytic changes after acute pancreatitis was induced by the intraductal injection of an autologous bile and trypsin mixture showed decreased platelet counts, decreased plasma fibrinogen levels, prolonged partial prothrombin time and increased fibrinogen degradation products. In addition, markers of hypercoagulation showed increased fibrin-opeptide A and decreased antithrombin III. The two markers of fibrinolysis showed increased Bβ15–42 immunoreactive peptide and decreased α2 antiplasmin. After the infusisn of Fut-175, the coagulo-fibrinolytic abnormalities, which were bserved during severe acute pancreatitis without infusion of Fut-175, were improved. Furthermore, Fut-175 could suppress the rise in fibrino-peptide A and Bβ15–42 immunoreactive peptide and decrease in antithrombin III and α2 antiplasmin. Thus, Fut-175 seems to be an effective inhitor of protease-mediated hypercoagulation and fibrinolysis in severe acute pancreatitis.

Management of pancreatic pseudocyst

The natural course, complications, and management of 37 patients with pancreatic pseudocyst treated at our institution were reviewed. The lesions were classified into three groups, cysts secondary to acute pancreatitis, to chronic pancreatitis, and to trauma. Spontaneous resolution or cyst diminution was observed in 75% of the patients with acute pancreatitis and trauma, but in only 33% of those with chronic pancreatitis. The interval until resolution or diminution in chronic pancreatitis was shorter than that in pseudocyst of other etiologies, but the incidence of complications in patients with chronic pancreatitis was not significantly higher than that among patients with other etiologies. Multiple complications were found only among the patients with chronic pancreatitis. Surgical management was performed in 25% of the patients with acute pancreatitis and trauma and 66% of the patients with chronic pancreatitis. The postoperative mortality rate was 10%. Reoperation was necessary in 6 of 7 patients who had undergone external drainage, including 3 patients treated with ultrasonography-guided percutaneous catheter drainage (US-PCD). These results suggest that it is necessary to closely monitor patients with chronic pancreatitis and/or external drainage, and in these patients it may become necessary to reoperate. US-PCD was useful as an emergency procedure in pseudocyst patients whose general condition was poor, despite the disadvantages of the piercing of adjacent organs by the catheter, infection, and pseudocyst recurrence.

Effects of a newly synthesized pancreatic protease inhibitor (PATM) on pancreatic microcirculation in experimental acute pancreatitis

SummaryPancreatic inschemia, especially due to pancreatic microcirculation disturbance, has been considered to trigger and aggravate acute pancreatitis. In this work experimental acute pancreatitis was produced by autologous bile and trypsin in mongrel dogs to study the time-course changes in systemic and local hemodynamics in association with disease progress. In addition, the effects of a new synthetic pancreatic protease inhibitor (PATM, 3 mg/kg/hr, i.v.) on systemic and local circulation were examined. In animals with untreated pancreatitis the mean baseline pancreatic microflow was 55.6 ± 17.0 ml/min/ 100g before the onset of pancreatitis and this decreased by 22% and 52% at 1 hr and 5 hr, respectively. The femoral arterial pressure and cardiac index also decreased during the 5 hr experiment at period in comparison with the respective preoperative levels. The portal venous flow showed a sharp reduction immediately after the onset of pancreatitis, staying at a low level thereafter. The pancreatic microflow was significantly improved by PATM treatment for the first 60 min and the portal venous flow for the first 120 min. PATM treatment prevented the decrease in femoral arterial pressure, although it failed to exert any appreciable effect upon the cardiac index. These findings suggest that intravenous administration of PATM might be of value for improving the pancreatic microflow and portal venous flow, at least in the early stage of experimental acute pancreatitis in dogs.