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The cellular events leading to acute pancreatitis are not well defined and the mechanism by which known aetiological factors initiate the disease process remains to be established. Inflammatory mediators have recently been implicated as potential early markers of disease severity and may help elucidate the pathophysiology of the disease. Oxidative stress is emerging as a common effector of the acinar cell injury in experimental acute pancreatitis and clinical findings indicate that neutrophil activation is a significant early event. In common with neutrophil-mediated tissue damage in states of tissue hypoperfusion, acute pancreatitis shows many features of an ischaemia-reperfusion injury. Increased levels of phospholipase A2 have been demonstrated; this enzyme induces synthesis of prostaglandins and platelet-activating factor, a potent inflammatory mediator. New therapeutic approaches to the complications of acute pancreatitis may be through manipulation of such mediators of inflammation.

Dropped gallstones may rarely become symptomatic, causing recurrent abscesses. Diagnosis is challenging due to unusual clinical presentations, myriad locations, and radiologically occult calculi. Even asymptomatic dropped gallstones may cause diagnostic confusion by masquerading as intraperitoneal neoplastic deposits. Radiologists should be aware of techniques for identifying and retrieving dropped gallstones and be wary of their complications and imitations in patients who have undergone laparoscopic cholecystectomy.

The aims of the study were to determine whether the platelet-activating factor antagonist Lexipafant could alter the clinical course and suppress the inflammatory response of human acute pancreatitis. In a double-blind, placebo-controlled study 83 patients were randomized to receive Lexipafant 60 mg intravenously for 3 days, or placebo. Clinical progression was assessed by daily Acute Physiology And Chronic Health Evaluation (APACHE) II score and organ failure score (OFS). The magnitude of the inflammatory response on days 1-5 was assessed by serial measurement of interleukin (IL) 8, IL-6, E-selectin, polymorphonuclear elastase-alpha1-antitrypsin (PMNE-alpha 1-AT), and C-reactive protein (CRP). At entry, patients receiving Lexipafant (n = 42) or placebo (n = 41) were matched for age and sex, aetiology, APACHE II score and OFS. The disease was classified as severe in 29 patients (APACHE II score eight or more). There was a significant reduction in the incidence of organ failure (P = 0.041) and in total OFS (P = 0.048) at the end of medication (72 h). During this time seven of 12 patients with severe acute pancreatitis who had Lexipafant recovered from an organ failure; only two of 11 with severe acute pancreatitis who had placebo recovered from an organ failure and two others developed new organ failure. Lexipafant treatment significantly reduced serum IL-8 (P = 0.038), and IL-6 declined on day 1. Plasma PMNE-alpha 1-AT complexes peaked on day 1; the gradual fall to baseline over 5 days observed in controls did not occur in patients given Lexipafant. No effect was observed on serum CRP. This study provides a rationale for further clinical trials with the potent PAF antagonist Lexipafant in human acute pancreatitis.