PANCREAS ALERTS
Pancreas 2002; 24:8-14.
Putative Pancreatic Cancer-Associated Diabetogenic Factor: 2030 MW Peptide.
Basso D, Valerio A, Seraglia R, Mazza S, Piva MG, Greco E, et al.
Department of Laboratory Medicine, Department of Clinical and Experimental
Medicine, University of Padova; CNR, CSSRCC, Padova; and Department of Medical
and Surgical Sciences, University of Padova, Padova, Italy.
Pancreatic adenocarcinoma causes diabetes mellitus by releasing factors which interfere with glucose metabolism. In this study, the authors verified, in isolated rat hepatocytes, the molecular weight of the fraction from the pancreatic cancer cell conditioned media which altered glucose metabolism and then ascertained, by means of matrix-assisted laser desorption/ionization mass spectrometry analysis, the presence of any common peptide in conditioned media and in the sera of patients with pancreatic cancer.
Sera were obtained from 14 patients having pancreatic cancer, 9 patients with chronic pancreatitis and 10 healthy subjects.
In rat hepatocytes, glucose metabolism was impaired by conditioned media from all the pancreatic cancer cell lines and by conditioned media with a molecular weight of less than 10,000 Da.
The authors concluded that a peptide at m/z 2030 may be a putative pancreatic cancer-associated diabetogenic factor.
Conditioned medium was obtained from MIA PaCa 2, PSK-1, PANC-1, and CAPAN-1 cell lines. Two fractions (molecular weight of less than 30,000 Da and less than 10,000 Da) were obtained from the patients' sera, from conditioned media and from non-conditioned media after a two-step ultrafiltration.
Rat hepatocytes were incubated with conditioned media and non-conditioned media .
The peptide profile of patients' sera, conditioned media and non-conditioned media were analyzed using matrix-assisted laser desorption/ionization mass spectrometry.
Two peptides (m/z 2030 and 2726) were found in conditioned media and the patients' sera. Only the peptide at m/z 2030 was found to be associated with the presence of diabetes.
Gut 2001; 48: 62-9.
Double blind, randomised, placebo controlled study of a platelet activating factor antagonist, lexipafant, in the treatment and preventiion of organ failure in predicted severe acute pancreatitis.
Johnson CD, Kingsnorth AN, Imrie CW, McMahon MJ, Neoptolemos JP, McKay C, et al.
University Surgical Unit, F Level, Centre Block, Southampton General Hospital, Tremona Road, Southampton, UK.
The aim of this multicenter UK study was to assess the role of a potent platelet activating factor (PAF) antagonist, lexipafant, in the treatment of severe acute pancreatitis.
The trial was designed as a randomized, double blind, placebo controlled, parallel group, phase III trial, involving 18 centres in the UK between November 1994 and August 1996.
58% of the patients in the placebo group and 57% in the lexipafant group developed one or more organ failures. Organ failure scores were reduced in the lexipafant group only on day 3; median change -1 (range from -4 to +8) versus 0 (range from -4 to +10) in the placebo group (p=0.04).
The conclusion of this study was that antagonism of PAF activity does not influence the course of severe acute pancreatitis. At the beginning of the study, the authors registered a high frequency of organ failure (44%) and this should question the appropriateness of its reduction as an adequate end point for the assessment of new therapies in predicted severe acute pancreatitis.
148 patients, eligible for analysis, were enrolled in the treatment group (lexipafant 100 mg/24 hours intravenously for 7 days began within 72 hours of the onset of symptoms); the placebo group was comprised of 138 patients.
The primary end point was the reduction of the frequency of systemic (organ failures: cardiovascular, respiratory, central nervous system failure, coagulopathy, and renal failure) or local (pancreatic necrosis, pancreatic abscess, pseudocyst, acute fluid collections) complications. Pre-study power calculations assumed that complications would be reduced from 40% to 24%.
Secondary end points were a) severity of organ failure, b) markers of the inflammatory response and c) mortality rate.
Systemic sepsis affected fewer patients in the lexipafant group (9.4% versus 2.7%, p=0.02).
Local complications occurred in 30% of the patients in the placebo group and in 20% of the patients in the lexipafant group (p=0.06); pseudocysts developed in 14% and 8% of the patients, respectively (p=0.02).
The number of deaths attributable to acute pancreatitis was not significantly different.
There were no differences in the absolute values of interleukin-8 and E-selectin between the two groups whereas both markers decreased more rapidly in the lexipafant group (both p<0.05).