PANCREAS ALERTS
Endoscopy 2001; 33:448-53.
Neutrophil activation and hyperamylasaemia after endoscopic retrograde cholangiopancreatography: potential role for the leukocyte in the pathogenesis of acute pancreatitis.
Mann DV, Kalu P, Foulds S, Edwards R, Glazer G.
Department of Surgery, St Mary's Hospital. London, United Kingdom.
Hyperamylasaemia occurs in up to 60% of patients following endoscopic retrograde cholangiopancreatography (ERCP) and, in a small proportion of patients (1-5%), acute pancreatitis may develop.
Forty-three patients undergoing elective ERCP were studied.
ERCP induced an increase in the amylase level above baseline in 41 of 43 patients. The 2-hour and 24-hour post-ERCP amylase levels were directly related (P<0.01).
The findings from this study indicate an association between neutrophil activation and hyperamylasaemia following ERCP, and suggest a role for this leukocyte in the pathogenesis of pancreatitis.
The authors evaluated the role of the neutrophil in post-ERCP hyperamylasaemia and acute pancreatitis by measuring circulating CD11b adhesion receptor expression which is an indicator of leukocyte activation.
Peripheral blood measurements of amylase activity and neutrophil CD11b content by flow cytometry were made immediately before ERCP, and at 2 and 24 hours after the procedure.
Baseline CD11b receptor status positively correlated with post-ERCP amylase activity (P<0.05) and this relationship was even greater when pancreatography was performed (P<0.01).
Three patients (7%) developed clinical acute pancreatitis, with post-ERCP amylase levels persistently elevated above 1000 IU/L.
Multiple linear regression identified CD11b expression as the most significant explanatory variable for amylase level after ERCP (multiple r = 0.74, P<0.01).
Further study of neutrophil characteristics may allow identification of individual susceptibility to ERCP-induced pancreatic injury.
Endoscopy 2001; 33:416-20.
Is endoscopic balloon dilation for removal of bile duct stones associated with an increased risk for pancreatitis or a higher rate of hyperamylasemia?
Bergman JJ, van Berkel AM, Bruno MJ, Fockens P, Rauws EA, Tijssen JG, et al.
Department of Gastroenterology, Academic Medical Center, University of Amsterdam. Amsterdam, The Netherlands.
The authors studied the rate of pancreatitis and asymptomatic hyperamylasemia after endoscopic balloon dilation and endoscopic sphincterotomy for removal of bile duct stones.
Patients with bile duct stones of all sizes were randomly selected to undergo endoscopic balloon dilation (8-mm dilation balloon) or endoscopic sphincterotomy.
Complete stone removal after a single ERCP was achieved in 88% of 93 endoscopic balloon dilation patients and in 93% of 87 endoscopic sphincterotomy patients (P=0.38).
There was no difference in the rate of pancreatitis between the endoscopic balloon dilation group and the endoscopic sphincterotomy group. Asymptomatic hyperamylasemia was observed more frequently after endoscopic balloon dilation.
J Biol Chem, 2001. [Papers In Press, published online ahead of print June 19, 2001]
Characterization of human mucin gene MUC4 promoter. Importance of growth factors and pro-inflammatory cytokines for its regulation in pancreatic cancer cells.
Unité INSERM 377, Lille cedex 59045.
Human mucin gene MUC4 encodes a large transmembrane mucin which is thought to play an important role in tumor cell biology and in ErbB2 signaling, and which is overexpressed in human pancreatic carcinomas.
In this report, the authors describe the structure and functional activity of the 5-flanking region, including 1.0 kb of the promoter.
The long 5-UTR (2.7 kb) is characterized by a high content of GC in its 3-end. The first TATA box was located at -2672/-2668. Multiple transcription start sites and a high density of putative binding sites for Sp1 (GC and CACCC boxes), AP-1/-2/-4, CREB, GATA, GR and STAT transcription factors were found within the 5-flanking region.
Two highly active fragments (-219/-1 and 2781/-2572) that drive MUC4 transcription in CAPAN-1 and CAPAN-2 cells were identified. Gel-retardation assays indicated that Sp1 and Sp3 bind to cognate cis-elements found in the 5-flanking region and that Sp1 transactivates whereas Sp3 inhibits the GC-rich region (-464/-1) in CAPAN-2 cells.
Together these results demonstrate that the 5-flanking region of MUC4 contains epithelial cell-specific, positive and negative regulatory cis-elements, that Sp1/Sp3 are important regulators of MUC4 basal expression and that its regulation in pancreatic cancer cells is complex and involves PKC, MAPK, NF-kappaB and JAK/STAT signaling pathways.
Pancreatitis was defined as epigastric pain combined with at least a threefold rise in serum amylase at 24 hours after the endoscopic retrograde cholangiopancreatography (ERCP).
Asymptomatic hyperamylasemia was defined as a threefold rise in serum amylase without epigastric pain.
There were 180 patients available for analysis.
Mechanical lithotripsy was used more frequently in the endoscopic balloon dilation group (31% vs. 13%, P=0.005).
Early complications occurred in 16 endoscopic balloon dilation patients (17%) and in 19 endoscopic sphincterotomy patients (22%) (P=0.46).
Pancreatitis was observed in seven patients in each group (8%). Logistic regression identified no significant predictors for the occurrence of pancreatitis.
Asymptomatic hyperamylasemia occurred in 21 endoscopic balloon dilation patients (23%) vs. seven endoscopic sphincterotomy patients (8%) (P=0.008). Logistic regression identified endoscopic balloon dilation as the only significant predictor for asymptomatic hyperamylasemia: odds ratio 2.9 (95% confidence interval 1.1 to 7.3).
Although asymptomatic hyperamylasemia is not a clinical entity, this finding may indicate that endoscopic balloon dilation causes more irritation of the pancreas than endoscopic sphincterotomy.
Perrais M, Pigny P, Ducourouble MP, Petitprez D, Porchet N, Aubert JP, Van Seuningen I.
Transcriptional activity of the promoter was assessed using pGL3-luciferase deletion mutants in two MUC4-expressing (CAPAN-1 and CAPAN-2) and one non-expressing (PANC-1) pancreatic cancer cell lines.
Activation of PKC with phorbol ester and treatment of cells with EGF and TGF-alphagrowth factors resulted in up-regulation of the promoter.
TNF-alpha and IFN-gammainflammatory cytokines had no or mild effect on MUC4 transcriptional activity when used alone. However, a very strong synergistic effect (10-12 fold activation) between IFN-gamma and TNF-alpha or IFN-gamma and TGF-alpha was obtained in CAPAN-2 cells.