Acute pancreatitis--from cellular signalling to complicated clinical course.
ABSTRACT Acute pancreatitis (AP) is a common disease that has a mild to moderate course in most cases. During the last decade, a change in diagnostic facilities as well as improved intensive care have influenced both morbidity and mortality in AP. Still, however, a number of controversies and unresolved questions remain regarding AP. These include prognostic factors and how these may be used to improve outcome, diagnostic possibilities, their indications and optimal timing, and the systemic inflammatory reaction (systemic inflammatory response syndrome--SIRS) and its effect on the concomitant course of the disease and potential development of organ failure. The role of the gut has been suggested to be important in severe AP, but has recently been somewhat questioned. Despite extensive research, pharmacological and medical intervention of proven clinical value is scarce. Various aspects on surgical interventions, including endoscopic sphincterotomy, cholecystectomy and necrosectomy, as regards indications and timing, will be reviewed. Last, but not least, are the management of late complications and long-term outcome for patients with especially severe AP.
Article: Quantitative measurement of P- and E-selectin adhesion molecules in acute pancreatitis: correlation with distant organ injury.[show abstract] [hide abstract]
ABSTRACT: To determine whether expression of P- and E-selectin molecules is associated with the development of systemic organ manifestations in acute pancreatitis (AP). Overproduction of inflammatory cytokines in AP induces expression of adhesion molecules, which may lead to increased leukocytic infiltration and tissue damage. Understanding the temporal expression of these molecules could afford better measures for therapeutic intervention. Acute pancreatitis was induced in 30-day-old female C57/ bI/6J mice by feeding a choline-deficient/ethionine-supplemented diet (n = 95). Mice were divided into three groups. Group I (n = 35) was used to study the biochemical and histologic manifestations of AP and to evaluate the neutrophilic infiltration by myeloperoxidase activity and immunofluorescence. Groups II (n = 35) and III (n = 25) were used to evaluate expression of P- and E-selectin by the dual radiolabeled monoclonal antibody technique. Biochemical and histologic evidence of AP developed in all mice. The inflammatory cytokine tumor necrosis factor-alpha gradually increased in serum as early as 18 hours, reaching more than 800-fold background levels by 72 hours. Biphasic P-selectin expression in the lung was seen with peaks at 24 and 48 hours; E-selectin expression peaked at 48 hours. CD18-positive leukocytes and increased myeloperoxidase activity in the lung were demonstrated at 24 hours, correlating with the onset of selectin upregulation. Histologic scoring of lung tissue demonstrated mild damage at 24 hours, with progressive injury occurring from 48 to 72 hours. In AP, the production of inflammatory cytokines precedes up-regulation of P- and E-selectin, whose expression coincided with the increased infiltration of CD18-positive cells and neutrophil sequestration in lung tissue. Temporally, these events correlate with evidence of histologic pulmonary injury and underscore the role of adhesion molecules as mediators of pathophysiologic events. This mechanistic pathway may afford novel therapeutic interventions in clinical disease by using blocking agents to ameliorate the systemic manifestations of AP.Annals of Surgery 03/2000; 231(2):213-22. · 7.49 Impact Factor
Article: Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock.[show abstract] [hide abstract]
ABSTRACT: Septic shock may be associated with relative adrenal insufficiency. Thus, a replacement therapy of low doses of corticosteroids has been proposed to treat septic shock. To assess whether low doses of corticosteroids improve 28-day survival in patients with septic shock and relative adrenal insufficiency. Placebo-controlled, randomized, double-blind, parallel-group trial performed in 19 intensive care units in France from October 9, 1995, to February 23, 1999. Three hundred adult patients who fulfilled usual criteria for septic shock were enrolled after undergoing a short corticotropin test. Patients were randomly assigned to receive either hydrocortisone (50-mg intravenous bolus every 6 hours) and fludrocortisone (50- micro g tablet once daily) (n = 151) or matching placebos (n = 149) for 7 days. Twenty-eight-day survival distribution in patients with relative adrenal insufficiency (nonresponders to the corticotropin test). One patient from the corticosteroid group was excluded from analyses because of consent withdrawal. There were 229 nonresponders to the corticotropin test (placebo, 115; corticosteroids, 114) and 70 responders to the corticotropin test (placebo, 34; corticosteroids, 36). In nonresponders, there were 73 deaths (63%) in the placebo group and 60 deaths (53%) in the corticosteroid group (hazard ratio, 0.67; 95% confidence interval, 0.47-0.95; P =.02). Vasopressor therapy was withdrawn within 28 days in 46 patients (40%) in the placebo group and in 65 patients (57%) in the corticosteroid group (hazard ratio, 1.91; 95% confidence interval, 1.29-2.84; P =.001). There was no significant difference between groups in responders. Adverse events rates were similar in the 2 groups. In our trial, a 7-day treatment with low doses of hydrocortisone and fludrocortisone significantly reduced the risk of death in patients with septic shock and relative adrenal insufficiency without increasing adverse events.JAMA The Journal of the American Medical Association 09/2002; 288(7):862-71. · 30.03 Impact Factor
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ABSTRACT: Thirty-seven patients treated for severe acute pancreatitis were investigated a mean of 6.2 years after the attack; 30 were found to be in good condition and 24 were working normally. Two-thirds of previously heavy drinkers had either reduced their intake considerably or become abstainers. The main complication observed on follow-up was diabetes mellitus, which affected 20 patients and required insulin treatment in nine. Of the remaining patients, four were taking oral antidiabetic agents and seven were on a strict diabetic diet. Before severe acute pancreatitis none had been diabetic. All patients who underwent resection of the pancreas developed diabetes. In 21 of 24 patients with over or imminent diabetes, pancreatitis had been primarily alcoholic in origin. Polyneuropathy, as diagnosed by clinical signs and/or neurophysiological tests, was observed in six patients, all of them heavy drinkers. It is concluded that patients with severe acute pancreatitis have a high chance of returning to normal activity and productive work. These results serve to encourage all those involved to persist with the exacting work involved in treating such patients.British Journal of Surgery 01/1994; 80(12):1583-6. · 4.61 Impact Factor