摘要:

Symposium participants: Guido Adler*Ulm, Germany; Rudolf W. Ammann**Zurich, Switzerland; Simmy Bank, New York, NY, U.S.A.; Peter Banks, Boston, MA, U.S.A.; Hans Beger, Ulm, Germany; Christoph Beglinger**Basel, Switzerland; Daniel Bimmler, Zurich, Switzerland; Dale E. Bockman, Atlanta, GA, U.S.A.; Philipp C. Bornman, Cape Town, South Africa; Edward L. Bradley III*Buffalo, NY, U.S.A.; Markus Buechler, Bern, Switzerland; Meinhard Classen, Munich, Germany; Eugene P. DiMagno*Rochester, MN, U.S.A.; Ulrich R. Foelsch*Kiel, Germany; Alan K. Foulis, Glasgow, Scotland; Charles Frey*Sacramento, CA, U.S.A.; Michael Fried**Zurich, Switzerland; Harald Goebell*Essen, Germany; Fred S. Gorelick, West Haven, CT, U.S.A.; James H. Grendell*New York, NY, U.S.A.; Lucio Gullo, Bologna, Italy; Niklaus Gyr**Basel, Switzerland; Hideo Harada, Okayama, Japan; Philipp U. Heitz**Zurich, Switzerland; Jan B. M. J. Jansen, Nijmegen, The Netherlands; Ingemar Ihse*Lund, Sweden; Günter Klöppel**Kiel, Germany; Günter Krejs, Graz, Austria; Peter Malfertheiner, Magdeburg, Germany; Solly I. N. Marks, Cape Town, South Africa; Joachim Mössner*Leipzig, Germany; Claus Niederau, Dusseldorf, Germany; Howard A. Reber, Los Angeles, CA, U.S.A.; Henri Sarles, Marseille, France; Martin Sarner, London, England; Manfred V. Singer*Mannheim, Germany; Michael Steer, Boston, MA, U.S.A.; Helge Worning, Copenhagen, Denmark.*Moderators of the group sessions.**Members of the organizing committee.

ISSN:0885-3177    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

The effects and safety of loxiglumide, a cholecystokinin-A (CCK-A) receptor antagonist, on advanced pancreatic cancer were investigated in humans. A perspective, controlled (2.4 g/day vs. placebo), randomized, double-blind, parallel-group study was performed in 64 patients affected by nonresectable histologically diagnosed pancreatic cancer. The patients were stratified according to sex and stage (A, T3/N0-N1/M0; B, T1-T2-T3/N0-N1/M1; C, relapse after surgical exeresis). Tumor size (by computed tomography scan) and mortality rate were evaluated as efficacy criteria. Clinical symptoms and physical signs, laboratory tests, and adverse reactions were checked every 6 weeks as efficacy/tolerability criteria. Forty-two male and twenty-two female patients were considered. A homogeneous distribution of the patients was demonstrated in the two treatment groups. Group C was not statistically evaluated for survival and tumor evolution because of its small number. Three patients dropped out for causes not related to the therapy. No toxic reactions to the drug were reported. Tumor size monitoring within groups A and B demonstrated a similar increase in both the loxiglumide and the placebo group. Survival in group A was higher than in group B (p= 0.0003). In group B, survival was lower in females (F) than in males (M) (F = 61.00 ± 6.47 days, M = 140.44 ± 22.15 days;p= 0.012), while survival by sex was similar in group A and in global analysis. Survival by treatment was similar for groups A and B. Survival by surgery was higher (p= 0.049) for surgical palliation than for nonoperated patients. The tumor grade affected survival but it did not vary by therapy. In conclusion, sure efficacy of loxiglumide in advanced pancreatic cancer was not demonstrated by our results. In consideration of its documented tumor growth inhibiting action, we suggest that loxiglumide be tested for recurrence prevention after resective surgery.

ISSN:0885-3177    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

HER-2/neu expression in pancreatic adenocarcinoma has been inconsistently reported and has not been fully evaluated with respect to histologic grade and tumor grade heterogeneity. We studied HER-2/neu expression in a series of 79 primary pancreatic carcinomas using immunohistochemical methods, with expression scored for each histologic grade represented in each tumor. We found significantly lower expression of HER-2/neu in poorly differentiated (PD) portions of tumors—those areas lacking glandular differentiation—compared to well-differentiated (WD) and moderately differentiated (MD) portions of tumors. Forty-two of 68 (62%) invasive tumors with WD or MD glands showed moderate or strong expression of HER-2/neu in WD/MD areas; only 6 of 32 (19%) invasive tumors with PD areas showed similar expression in PD. In mutually exclusive patient sets, we also found a statistically different prevalence of HER-2/neu expression in patients with PD (6/32 cases; 19%) and without PD (29/47 cases; 62%) tumors (p< 0.001). Twenty-three cases had directly comparable areas of PD versus MD or WD. In 19 of 23 cases HER-2/neu expression was graded comparatively lower (or negative) in areas of PD than in MD or WD. Overall 46 of 79 cases (58%) showed moderate to strong HER-2/neu expression inclusive of all histologic grades, and 63 of 79 (80%) cases were HER-2/neu positive, if including weak or focal staining. There was no significant difference in the survival of patients with HER-2/neu-positive versus-negative tumors or in patients with versus without PD tumors. We have confirmed that although HER-2/neu gene expression is common to many pancreatic carcinomas, it is not common to tumors lacking glandular differentiation. HER-2/neu gene expression could not be related to survival differences—perhaps due to overall poor survival within adenocarcinomas of the pancreas—but the pattern of HER-2/neu expression suggests a relationship to glandular differentiation and early oncogenesis.

ISSN:0885-3177    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Carcinoma of the pancreas is the fifth leading cause of cancer death, with the majority of patients presenting with unresectable disease. Research into new adjuvant therapies is hampered by the lack of suitable in vivo and in vitro models. We have examined the potential of seven pancreatic carcinoma cell lines to grow as multicellular tumor spheroids (MTS). Three of seven (43%) cell lines were scored positive for MTS formation, and the growth characteristics for spheroid models of the cell lines PANC1 and MIAPaCa2 are presented. Implantation of PANC1 MTS into the pancreas of athymic nude mice produces tumors with reproducible growth characteristics and histology.

ISSN:0885-3177    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Recent studies have shown that cholecystokinin (CCK) is involved in the induction and development of acute pancreatitis in experimental animals. In the present study we determined basal plasma CCK concentrations by a specific and sensitive radioimmunoassay using antiserum OAL656 in 17 patients with acute pancreatitis due to gallstone in the common bile duct (n= 7), alcoholic (n= 4), post endoscopic retrograde pancreatography (n= 1), and unknown causes (n= 4), and 37 patients with cholelithiasis (n= 18) and choledocholithiasis (n= 19). Plasma CCK concentrations in patients with gallstone pancreatitis on hospital day 1 (mean ± SEM, 6.78 ± 1.39 pM) were significantly higher than those in patients with other causes (1.33 ± 0.16 pM) or in 20 healthy control subjects (1.55 ± 0.11 pM). There was no relationship between plasma CCK and serum pancreatic enzyme levels, the severity of acute pancreatitis, or serum bilirubin concentrations. Plasma CCK levels in patients with acute symptomatic cholelithiasis (n= 7; 4.35 ± 0.90 pM) and choledocholithiasis (n= 8; 4.52 ± 1.17 pM) were significantly higher than those in patients without symptoms (cholelithiasis,n= 11, 1.40 ± 0.17 pM; choledocholithiasis,n= 11, 1.88 ± 0.49 pM) but tended to be lower than those in patients with gallstone pancreatitis. These present observations suggest that the increase in plasma CCK levels in gallstone pancreatitis appears not to be the cause but to be the result of gallstone pancreatitis probably due to a transient disturbance of bile flow into the duodenum by stones or edema of the bile duct. Our present results provide some evidence for the usefulness of CCK receptor antagonists for the treatment of biliary colics and acute pancreatitis.

ISSN:0885-3177    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

The influence of bile on the release of cholecys-tokinin (CCK) and, thereby, on the regulation of exocrine pancreatic function and growth is unsettled. The aim of this study was to elucidate the effect of long-term diversion of bile from the upper small intestine on CCK release and on the pancreas, liver, and gastrointestinal tract. A surgical biliodigestive shunt was performed in rats, diverting the bile flow directly to the middle of the small intestine. The animals were killed after 4 or 12 weeks. Plasma CCK and trophic effects on the pancreas, liver, and gastrointestinal tract were determined, as were the trypsin and chymotrypsin contents in the intestine. The CCK concentration in plasma increased 10-fold at both time points studied. The pancreas doubled its weight from 4 weeks onward. Also, pancreatic protein, DNA, and amylase contents were increased throughout the study. The liver and gastrointestinal tract were unaffected. Intraluminal bile plays a role in the feedback regulation of CCK release and is involved in this way in the control of pancreatic growth but has no similar effects on the liver or gastrointestinal tract.

ISSN:0885-3177    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Activation of digestive zymogens by lysosomal enzymes has been suggested as a triggering event in acute pancreatitis (AP). Chloroquine (CQ), a weak base that accumulates in the lysosomes and increases their pH, can inhibit the activity of lysosomal enzymes. In the present study, we examined the effect of CQ on choline-deficient, ethionine-supplemented (CDE) diet-induced AP. CQ-diphosphate (15–50 mg • kg−1) or vehicle was given intraperitoneally at 0, 24, and 48 h to female CD1 mice that were fed with either normal diet or CDE diet. For mortality studies, animals were observed for 168 h. Serum and pancreas samples were collected from animals sacrificed 56 h after the start of the CDE diet. Treatment with CQ at 50 mg • kg−1significantly (p< 0.05) improved the survival of mice with CDE diet-induced AP. In the normal pancreas, CQ decreased the specific activity of lysosomal enzymes cathepsin B1, β-hexosaminidase, β-glucuronidase, and acid phosphatase. In the pancreas with AP, CQ did not modify the activity of cathepsin B1, whereas it increased the latency of all enzymes. In conclusion, our results confirm the beneficial effect of CQ on survival of mice with CDE diet-induced AP and suggest that this effect of CQ may be due to its stabilizing action on lysosomes.

ISSN:0885-3177    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

We investigated the effects of the xanthine derivative propentofylline on lung injury in rats with cerulein-induced acute pancreatitis and endotoxemia. Pancreatitis was induced by four intramuscular injections of cerulein (50 μg/kg at 1-h intervals). Pancreatitis rats were injected intraperitoneally with 30 mg/kg lipopolysaccharide (LPS) 6 h following the first cerulein injection as a septic challenge. Propentofylline (50 mg/kg) was injected intravenously 15 min before the administration of LPS. Rats were divided randomly into five experimental groups: group I, normal rats; group II, pancreatitis; group III, LPS injection; group IV, pancreatitis and LPS injection; and group V, pancreatitis and LPS injection with propentofylline pretreatment. Serum amylase concentrations in groups II, IV, and V increased significantly 8 h after the first cerulein injection compared to those in groups I and III. Serum tumor necrosis factor (TNF)-α concentrations, cytokine-induced neutrophil chemoattractant (CINC) concentrations in serum or bronchoalveolar (BAL) fluid, lung myeloperoxidase (MPO) activity, and extent of pulmonary polymorphonuclear cell infiltration in group IV were significantly higher than those observed in group III. Pretreatment with propentofylline inhibited the rise in TNF-α levels (group V). However, propentofylline did not prevent the elevation of CINC levels in group V. In contrast, propentofylline reduced lung MPO and pulmonary PMN infiltration in group V. In addition, lung compliance was improved by pretreatment with propentofylline. These results suggest that propentofylline attenuates lung injury in an experimental model of pancreatitis complicated by endotoxemia but has differential effects on cytokine production.

ISSN:0885-3177    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Effects of green tea catechins (GTC) on cerulein-induced acute pancreatitis in rats were examined. The acute pancreatitis induced by cerulein (cerulein pancreatitis) was characterized by interstitial edema and vacuolation. When cerulein pancreatitis was induced, prior administration of 0.1% GTC in drinking water for 1 week before the induction significantly decreased the wet weight of the pancreas, the serum level of amylase, and the tissue concentration of lipid peroxides in the pancreas compared with those in nonmedicated rats supplied with plain tap water only. Furthermore, the pancreatic tissue alterations of the medicated rats were milder than those of the nonmedicated rats. These data suggest that GTC have a protective effect on the pathogenesis of cerulein pancreatitis.

ISSN:0885-3177    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Portal hypertension (PH) is associated with a hyperdynamic splanchnic circulation, partially mediated by nitric oxide-dependent mechanisms. The aim of the present study was to evaluate the influence of PH and nitric oxide on pancreatic islet blood flow. PH was induced by a calibrated stenosis of the portal vein in male Sprague-Dawley rats. Control rats were sham-operated. Ten days later pancreatic, duodenal, colonic, and arterial hepatic blood flows were measured with micro-spheres. All splanchnic blood flow values were markedly increased in the PH rats. The fraction of whole pancreatic blood flow diverted through the islets increased from ∼5 to 15%. Intravenous administration of the nitric oxide synthase inhibitorNG-nitro-L-arginine (25 mg/kg body weight) in rats with PH 10 min before blood flow measurements decreased pancreatic, duodenal, colonic, and arterial hepatic blood flow to control values. Pancreatic islet blood flow was also decreased, but more markedly than that of the whole pancreas. Pancreatic islet morphology was normal, and the rate of islet cell replication was not influenced. PH induced a preferential increase in pancreatic islet blood flow, which is likely to be associated with an increased production of nitric oxide.

ISSN:0885-3177    

出版商:OVID    

年代:1997

数据来源: OVID