PANCREAS ALERTS
Am J Gastroenterol 2003; 98:2182-6. (AN 22934153, PMID 14572565)
Comparison of two dosing regimens of gabexate in the prophylaxis of post-ERCP pancreatitis.
Masci E, Cavallini G, Mariani A, Frulloni L, Testoni PA, Curioni S, et al.
Servizio di Gastroenterologia ed Endoscopia Digestiva, Ospedale S. Raffaele, Universita' Vita e Salute. Milan, Italy.
A continuous 13-h infusion of gabexate starting 30-90 min before endoscopic cholangiopancreatography (ERCP) can reduce postprocedural pancreatitis, the onset of which is generally observed within the first 6 h after ERCP. This study was designed to verify whether a 6.5-h infusion of gabexate was as effective as a 13-h infusion, at the same concentration, for reducing the incidence of post-ERCP pancreatitis (primary endpoint) and pancreatic hyperenzymemia and pain (secondary endpoints).
A total of 434 patients (201 male and 233 female; mean age 63.9 yr, range 18-96 yr) scheduled for ERCP were prospectively recruited in 25 Italian centers. Patients were double-blindly randomized to two treatment groups.
Acute pancreatitis was observed in 8 patients (1.8%); 3 of 214 patients in group I (1.4%) and 5 of 220 patients in group II (2.2%). Serum amylase and lipase values over time, peak levels of the two enzymes, pancreatic pain, and need for analgesics did not significantly differ between the two groups.
These results suggest that a 6.5-h infusion of gabexate (for a total of 500 mg) is not less effective than a 13 h infusion, with evident savings.
All subjects enrolled were first treated with a 500-mg continuous intravenous infusion of gabexate, starting 30 min before the endoscopic maneuvers and continuing up to 6.5 h after it. Over the next 6.5 h, 214 patients (group I) continued the infusion of gabexate (for a total of 1 g over 13 h) and 220 patients (group II) were given placebo (saline solution).
Ann Surg 2003; 238:765-71. (AN 22939287, PMID 14578741)
Systemic intravenous infusion of bovine hemoglobin significantly reduces microcirculatory dysfunction in experimentally induced pancreatitis in the rat.
Strate T, Mann O, Kleinhans H, Schneider C, Knoefel WT, Yekebas E, et al.
Departments of General Surgery. Hamburg, Germany.
Stasis of the pancreatic microcirculation initiates and aggravates acute pancreatitis. Hydroxyethyl-starch (HES) has been shown to improve pancreatic microcirculation. Similarly, bovine hemoglobin might improve rheology due to its colloid effect, but additionally supplies oxygen to oxygen depleted pancreatic tissue.
In Wistar rats, severe acute pancreatitis was induced by administration of glucodeoxycholic acid i.d. and cerulein i.v.. Pancreatic microcirculation was continuously monitored by fluorescence microscopy. Fifteen minutes after the initiation of acute pancreatitis, animals received either 0.8 mL bovine hemoglobin (Oxyglobin), HES, or 2.4 mL 0.9% NaCl i.v. at random. After 6 hours, animals were killed and histopathological damage of the pancreas was assessed using a validated histology score (0-16).
In comparison to controls, pancreatic microcirculation improved significantly in the HBOC group (mean difference of capillary density 31.4%; standard error 5.6%; P<0.001; 95% confidence interval for difference 17.5-45.3%). HES was not as effective as HBOC substitution. The histology score revealed less tissue damage in the HBOC group [6.25 vs. 9.25 (3-8.5 vs. 8-10.75; P<0.001)] in comparison to controls and also in comparison to the HES group [6.25 vs. 8 (3-8.5 vs. 6.5-10.25; P<0.006)].
The authors concluded that in severe acute pancreatitis, single i.v. injection of bovine hemoglobin improves pancreatic microcirculation and reduces tissue damage.
In this study the authors evaluated the effectiveness of bovine hemoglobin on pancreatic microcirculation and outcome in experimental acute rodent pancreatitis.
Hepatogastroenterology 2003; 50:1665-8. (AN 22933898, PMID 14571812)
Pancreatitis associated with pancreaticobiliary maljunction.
Kamisawa T, Matsukawa M, Amemiya K, Tu Y, Egawa N, Okamoto A, Aizawa S.
Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital. Tokyo, Japan.
Pancreaticobiliary maljunction is a rare anomaly, but causes various pathological conditions in the biliary tract and the pancreas.
A total of 100 patients with pancreaticobiliary maljunction were reviewed. Clinical findings and cholangiopancreatographic results in patients with acute or chronic pancreatitis associated with pancreaticobiliary maljunction were analyzed.
Of 100 patients, 14 had pancreatic disorders: acute pancreatitis (n = 3), chronic pancreatitis (n = 5), hyperamylasemia (n = 4), and pancreatic carcinoma (n = 2). The acute pancreatitis was mild (n = 3) and relapsing (n = 2). In patients with chronic pancreatitis, pancreatic stones (n = 2) and radiolucent protein plugs (n = 2) were detected only in the dilated common channel or in the main pancreatic duct near the common channel. Two patients received cyst-duodenostomy in the infant developed chronic pancreatitis 11 and 27 years later.
The authors concluded that acute or chronic pancreatitis was sometimes associated with pancreaticobiliary maljunction. These pancreatitis cases showed different clinical and pancreatographic findings from others. These differences might be due to the peculiar mechanism that they were induced by bile reflux into the pancreatic duct via the anomalous connection.
In this study the authors aim at clarifying the features of pancreatitis associated with pancreaticobiliary maljunction.
Pancreas 2003; 27:332-6. (AN 22938248, PMID 14576497)
Mutations of the CFTR Gene in pancreatic disease.
Pezzilli R, Morselli-Labate AM, Mantovani V, Romboli E, Selva P, Migliori M, et al.
Department of Internal Medicine and Gastroenterology, University of Bologna. Bologna, Italy.
An association has been found between CFTR gene mutations and chronic pancreatitis; however, there is a lack of information about the frequency of CFTR gene mutations in acute pancreatitis and in pancreatic cancer.
Ninety-eight consecutive patients were studied and divided into 3 groups: 34 patients with acute pancreatitis, 46 patients with chronic pancreatitis, and 18 patients with pancreatic cancer. The mutation analysis of the CFTR gene was carried out using diagnostic commercial kits for the simultaneous detection of 29 mutations and Tn polymorphism.
Among the 98 patients studied, 12 (12.2%) had CFTR gene mutations: 2 of the 34 patients (5.9%) with acute pancreatitis, 9 of the 46 (19.6%) with chronic pancreatitis, and 1 of the 18 (5.6%) with pancreatic cancer. All the mutations were found in heterozygosis (2 DeltaF508, 1 W1282X, and 9 T5 allele).
The authors concluded that this prospective study adds further information about the frequency of CFTR mutations in patients with a single episode of acute pancreatitis. Furthermore, the results suggest an association of CFTR gene mutations with chronic alcoholic pancreatitis and emphasize the need for a multicenter study, possibly multinational, to conclusively establish the role of CFTR mutations as a genetic susceptibility factor for this disease.
The authors prospectively evaluate the prevalence of CFTR gene mutations in acute pancreatitis, chronic pancreatitis, and pancreatic cancer.
Eur J Nucl Med Mol Imaging. 2003 October 31 [Epub ahead of print]. (PMID 14593501)
Neurofunctional imaging of the pancreas utilizing the cholinergic PET radioligand [(18)F]4-fluorobenzyltrozamicol.
Clark PB, Gage HD, Brown-Proctor C, Buchheimer N, Calles-Escandon J, Mach RH, Morton KA.
Nuclear Medicine Section, Department of Radiology, Wake Forest University School of Medicine.Winston-Salem, NC, USA.
The pancreas is one of the most heavily innervated peripheral organs in the body. Parasympathetic and sympathetic neurons terminate in the pancreas and provide tight control of endocrine and exocrine functions.
Using fluorine-18 4-fluorobenzyltrozamicol (FBT), which binds to the presynaptic vesicular acetylcholine transporter, positron emission tomography scans were performed in four adult mice, two adult rhesus monkeys, and one adult human.
In these mammals, the pancreas is intensely FBT avid, with uptake greater than in any other organ at 30, 60, and 90 min. The maximum standardized uptake value (SUV) ratios of pancreas to liver, for example, ranged from 1.4 to 1.7 in rhesus monkeys (mean 1.6; median 1.7) and from 1.9 to 4.7 (mean 3.24; median 3.02) in mice. The maximum SUV ratio of pancreas to liver in the human was 1.8.
On the basis of these suggest the authors suggest that neuroreceptor imaging of the pancreas in vivo is feasible in animal models and humans. This imaging could allow researchers to interrogate functions under control of the autonomic nervous system in the pancreas, with applications possible in transplanted and native pancreata. Also, as beta cell function is intimately related to parasympathetic cholinergic input, FBT activity in the pancreas may correlate with insulin-producing beta cell mass. This could provide a method of in vivo imaging in animal models and humans for diabetes research.
The authors aimed to determine whether the pancreas can be imaged with a radioligand that binds to specific neuroreceptors.
Biol Neonate 2003; 84:287-92. (AN 22953908, PMID 14593238)
Vascular endothelial growth factor and angiogenin levels during fetal development and in maternal diabetes.
Lassus P, Teramo K, Nupponen I, Markkanen H, Cederqvist K, Andersson S.
Department of Obstetrics and Gynecology, University of Helsinki, Finland.
In this study the authors evaluated the concentrations of vascular endothelial growth factor (VEGF) and angiogenin in the umbilical cord blood from 14 fetuses with erythroblastosis or alloimmune thrombocytopenia and at birth from 28 preterm fetuses, from 42 healthy term fetuses, and from 24 term fetuses born to mothers with insulin-treated diabetes.
A correlation appeared between VEGF and angiogenin levels (r=0.44, P=0.038). The gestational age correlated with both VEGF (r=0.38, P=0.0008) and angiogenin levels (r=0.80, P=0.0001). The concentration of VEGF was lower in fetuses born to mothers with insulin-treated diabetes than in the healthy term fetuses (P=0.0028), but this difference was absent for angiogenin (P>0.05).
The authors concluded that in umbilical cord plasma, a developmental increase was evident in concentrations of VEGF and angiogenin during the last trimester of gestation; the umbilical cord VEGF level was lower in term fetuses born to mothers with diabetes than in term fetuses of healthy mothers may be associated with an aberrant fetal vascular development in diabetic pregnancies.