PANCREAS ALERTS
Scand J Gastroenterol 2002; 37(11):1328-33. (AN 22353140, PMID 12465733)
Effects of acute pancreatic duct obstruction on pancreatic perfusion: implication of acute pancreatic duct decompression.
Shi CX, Chen JW, Carati CJ, Schloithe AC, Toouli J, Saccone GT.
Dept. of General and Digestive Surgery, Flinders Medical Centre, Flinders University of South Australia. Bedford Park, Australia.
Acute pancreatitis can result in pancreatic ischaemia and necrosis. Pancreatic duct obstruction may be the first step leading to ischaemia in acute pancreatitis. Nitric oxide can attenuate acute pancreatitis through improvement of compromised pancreatic perfusion.
Fifteen Australian possums were studied and were randomly assigned to two groups: 6 animals (group A) were subjected to 30 min of pancreatic duct obstruction and 60 min of pancreatic duct decompression and 9 animals (group B) were subjected to 120 min of pancreatic duct ligation and 60 min of pancreatic duct decompression.
Pancreatic duct pressure increased following pancreatic duct ligation. Pancreatic perfusion was significantly (P<0.01) reduced to baseline following 30 and 120 min of pancreatic duct ligation, respectively.
The authors confirmed previous studies in animals and in humans which showed that in acute pancreatitis due to obstructive causes, early decompression of the pancreatic duct may prevent early pancreatic ischaemia.
In this study, the authors determined if pancreatic duct obstruction altered pancreatic perfusion and if pancreatic duct decompression or L-arginine administration reversed this change.
Six animals of group B were subjected to intravenous L-arginine (100 microg/kg) at the end of 120 min of ligation and at the end of pancreatic duct decompression. Pancreatic perfusion, pancreatic duct pressure and blood pressure were continuously monitored.
After 60 min of pancreatic duct decompression, pancreatic perfusion was restored (P<0.02) to baseline in the 30-min group. However, after 120 min pancreatic duct ligation, pancreatic perfusion remained depressed.
L-arginine administration after 120 min of pancreatic duct ligation transiently increased pancreatic perfusion (P<0.03) from baseline. This effect was reproduced if L-arginine was administered at the end of decompression (P<0.05).
Scand J Gastroenterol 2002; 37(11):1313-20. (AN 22353138, PMID 12465731)
Differentiation of pancreatic tumours by conventional ultrasound, unenhanced and echo-enhanced power Doppler sonography.
Rickes S, Unkrodt K, Neye H, Ocran KW, Wermke W.
Dept. of Gastroenterology, Hepatology and Endocrinology, University Hospital Charite (Campus Mitte). Berlin, Germany.
Echo-enhanced power Doppler sonography is a non-invasive and increasingly used procedure for differentiating between pancreatic tumours. However, the diagnostic accuracy of this method as compared to conventional ultrasound or unenhanced power Doppler sonography has never been investigated in a large prospective controlled study.
In this study, 137 patients selected from 190 consecutive subjects with clinical suspicion of pancreatic tumour were included. Sonography was performed by an experienced examiner blind to the patients' clinical diagnoses. The exact diagnosis was based on histological evidence from biopsy examination (surgical and fine needle biopsy) or on a follow-up of at least 18 months.
Of the 137 patients, 47 had pancreatic cancer, 41 had masses associated with pancreatitis, 17 had neuroendocrine tumours, 12 had cystic lesions of the pancreas, and 10 had other pancreatic diseases. A normal pancreas was found in 10 patients.
The authors concluded that echo-enhanced power Doppler sonography has a high sensitivity and specificity in the differential diagnosis of pancreatic tumours even if histology is the standard of reference.
The sensitivity of echo-enhanced power Doppler sonography with respect to diagnosing pancreatic carcinoma was 87% and its specificity 94%. The corresponding values for chronic pancreatitis were 85% and 99%, respectively.
Ann Surg 2002; 236(6):738-49. (AN 22340554, PMID 12454512)
VEGF-RII influences the prognosis of pancreatic cancer.
Buechler P, Reber HA, Buechler MW, Friess H, Hines OJ.
Department of Surgery, UCLA School of Medicine, University of California, Los Angeles, California 90095-6904, USA.
Vascular endothelial growth factor VEGF and its receptors (VEGF-RI and -RII) are the predominant regulators of tumor neoangiogenesis, a key element for tumor growth and progression. However, VEGF receptor expression has been thought to be limited to endothelial cells, thus limiting the possibility of targeting it for therapy in pancreatic cancer.
Protein localization and mRNA were studied in pancreatic cancer specimens, the normal pancreas, human pancreatic cancer cell lines, and an endothelial cell line. Cell proliferation was determined by 3H thymidine uptake. Both VEGF receptors were genetically eliminated by antisense technology. The same approach was used in a murine model of pancreatic cancer in a therapeutic approach.
VEGF-RI mRNA and VEGF-RII mRNA were expressed in 17 and 15 of 24 pancreatic cancer samples, respectively. VEGF receptors were found not only in blood vessels but also in pancreatic cancer cells. VEGF-RII expression correlated with poor tumor differentiation and was associated with poorer survival, while VEGF-RI expression did not correlate.
The authors concluded that the VEGF/VEGF-RII pathway regulates angiogenesis and local tumor growth and metastatic spread in pancreatic cancer. Genetic targeting of VEGF-RII blocks local growth and metastatic spread of pancreatic cancer cells in vivo and therefore offers a potential new therapeutic option for patients with this disease.
In this study, the authors evaluated whether the (VEGF) pathway can be used as a target for effective treatment of pancreatic cancer.
VEGF treatment led to extensive growth stimulation in six of seven pancreatic cancer cell lines and this was completely inhibited by antisense treatment against VEGF-RII.
Liposome-mediated gene transfer in nude mice with pancreatic tumors markedly reduced local tumor growth and decreased metastatic tumor spread.
Dig Dis Sci 2002; 47(11):2416-21. (AN 22339529, PMID 12452372)
Germline mutations in CFTR and PSTI genes in chronic pancreatitis patients.
Gaia E, Salacone P, Gallo M, Promis GG, Brusco A, Bancone C, Carlo A.
Struttura Complessa di Gastroenterologia, Dipartimento di Clinica Medica, Azienda Ospedaliera San Luigi Gonzaga. Torino, Italy.
Mutations in the cationic trypsinogen, cystic fibrosis transmembrane conductance regulator (CFTR) and pancreatic secretory trypsinogen inhibitor (PSTI) genes have recently been associated with chronic pancreatitis.
In idiopathic pancreatitis, a significant increase was found in mutation frequency both in the CFTR gene (13%) and the N34S mutation in the PSTI gene (3.9%) as well as an increase in familial disposition to pancreatic disorders.
In conclusion, mutations in the genes investigated are involved in causing idiopathic pancreatitis. Such mutations have no connection either with age at onset or with the clinical course of the disease.
The authors investigated the frequency of CFTR and PSTI gene mutation in patients with idiopathic and alcoholic chronic pancreatitis, the clinical course of patients with these two kinds of disease, and examined the clinical differences between carriers and non-carriers of the mutations.
In alcohol-induced pancreatitis, an increase in calcification, exocrine insufficiency and diabetes mellitus was observed.
Gastroenterology 2002; 123(6):1857-64. (AN 22341403, PMID 12454843)
Genotype and phenotype correlations in patients with cystic fibrosis and pancreatitis.
Durno C, Corey M, Zielenski J, Tullis E, Tsui LC, Durie P.
Programmes in Integrative Biology, The Research Institute, The Hospital for Sick Children. Toronto, Ontario, Canada.
Pancreatitis is known to occur in some patients with cystic fibrosis, but the prevalence, natural history, and genotypic basis are unclear.
In this study, the authors identified patients with cystic fibrosis from a computerized database. A chart audit identified all patients with cystic fibrosis and pancreatitis.
Among 1075 patients with cystic fibrosis, 87% were pancreatic insufficient at diagnosis, 3% were pancreatic sufficient but developed pancreatic insufficiency after diagnosis, and 10% have remained pancreatic sufficient. No patients with pancreatic insufficiency developed pancreatitis.
In conclusion, patients with cystic fibrosis having pancreatic sufficiency carry at least one mild mutant allele and are at a significant risk of developing pancreatitis. Symptoms of pancreatitis may precede the diagnosis of cystic fibrosis. Pancreatitis is associated with an otherwise mild cystic fibrosis phenotype.
The authors examined a well-defined cohort of patients with cystic fibrosis in order to answer these questions.
Nineteen patients (17.3%) with pancreatic sufficiency experienced one or more attacks of pancreatitis.
The mean age at diagnosis of pancreatitis was 22.7 years and pancreatitis was recognized before the diagnosis of cystic fibrosis in 63.2% of the patients.
The diagnosis of cystic fibrosis in pancreatic-sufficient patients, with and without pancreatitis, was established at a significantly older age than in those with pancreatic insufficiency (P<0.001).
Genotyped patients with pancreatic insufficiency carried two severe mutant alleles. All genotyped patients with pancreatic sufficiency and pancreatitis carried at least one mild mutation. No specific genotype was predictive of pancreatitis.
Gastrointest Endosc 2002; 56(6):880-4. (AN 22335909, PMID 12447302)
Usefulness of endoscopic observation of the main duodenal papilla in the diagnosis of sclerosing pancreatitis.
Unno H, Saegusa H, Fukushima M, Hamano H.
The Second Department of Internal Medicine and the Department of Laboratory Medicine, Shinshu University School of Medicine. Matsumoto, Japan.
In the literature, there are no descriptions of the appearance of the main duodenal papilla in sclerosing pancreatitis.
The authors explored the characteristics of the main duodenal papilla in patients with sclerosing pancreatitis.
Macroscopic findings at ERCP with reference to the main duodenal papilla of 17 patients with sclerosing pancreatitis were compared with those of 24 patients with normal ERCP findings, 11 with chronic pancreatitis, 13 with primary sclerosing cholangitis, 21 with pancreatic cancer and 18 with bile duct cancer.
Severe swelling of the main duodenal papilla was observed in 7 (41%) of the17 patients with sclerosing pancreatitis. The total score for the degree of swelling in patients with sclerosing pancreatitis was significantly higher than that in patients with a normal ERCP, chronic pancreatitis, primary sclerosing cholangitis, pancreatic cancer and bile duct cancer (P<0.01).
In conclusion, a swollen main duodenal papilla was a characteristic finding in patients with sclerosing pancreatitis. T-lymphocyte infiltration is present in the swollen main duodenal papilla. These features may be useful in the diagnosis of sclerosing pancreatitis.
Endoscopic photographs of the papilla were reviewed retrospectively by 3 observers blinded to the underlying pancreaticobiliary pathology. The degree of swelling was scored in all patients.
Biopsy specimens from swollen papillae were assessed histopathologically in 3 patients with sclerosing pancreatitis.
T-lymphocyte infiltration of the papilla was evident in the biopsies from 3 patients with sclerosing pancreatitis.