Pharmacologic inhibition of ICE significantly improves the overall severity of and the death rate in SAP. A substantial reduction of neutrophil-mediated tissue injury in pancreas and lung seems to contribute to the beneficial effects of this approach. Moreover, ICE inhibition is still effective after a therapeutic window of 12 hours. Based on the current findings, future studies on the clinical application of ICE-inhibiting substances in acute pancreatitis seem to be promising.

Serum interleukin-18 concentrations are significantly elevated in patients with acute pancreatitis complicated by pancreatic necrosis and remote organ failure. The present data suggest an important role of caspase-1 dependent cytokine activation in the pathomechanism of severe acute pancreatitis beyond the experimental setting. In this context, interleukin-18 may serve as a potential target for new therapeutic approaches.

SUMMARY:There is recent experimental evidence that inhibition of caspase-1/interleukin-1␤ converting enzyme (ICE) significantly ameliorates overall severity and survival in severe acute experimental pancreatitis. However, little is known about the effects of this approach on the dynamics and mechanisms of local acinar cell damage, which we aimed to investigate in the present study. Severe acute pancreatitis (SAP) was induced by retrograde infusion of 4% sodium taurocholate in rats treated with isotonic saline or a highly selective, irreversible inhibitor of ICE. After 3, 6, and 24 hours, 3 and 7 days, acinar cell death by necrosis and apoptosis, as well as intrapancreatic and systemic interleukin-1␤ (IL-1␤) and tumor necrosis factor-␣ (TNF-␣) expression, was assessed. Treatment with the ICE inhibitor significantly reduced the extent of acinar cell necrosis accounting for major parenchymal destruction. In contrast, apoptosis was confined to the postacute course of the disease and was closely related to tubular complex formation, both remaining unchanged. Whereas intrapancreatic IL-1␤ mRNA expression was highly up-regulated in both treated and untreated animals, active IL-1␤ protein expression and subsequent neutrophil tissue infiltration was dramatically decreased in the ICE-inhibited group. Parallel to the onset of enhanced apoptotic acinar cell death and tubular complex formation, TNF-␣ mRNA and protein expression was up-regulated, with levels being lower in ICE inhibitor-treated rats. We conclude that activation of caspase-1/ICE plays a central role in the progression of acinar cell death by necrosis in SAP. Herein, IL-1␤-mediated neutrophil infiltration seems to be a crucial step in enhanced cellular destruction. In contrast, acinar cell apoptosis contributes to ductal transformation and is independent of this mechanism, but may be influenced by TNF-␣ (Lab Invest 2001, 81:1001-1013.

The study presented a case of a patient with a glomus tumor of the stomach, a mesenchymal neoplasm manifesting with upper gastrointestinal bleeding (Forrest IB). The patient was operated twice. First, he underwent elective laparotomy, during which Billroth I (Rydygier's method) gastric resection was performed. This his was followed by Billroth II resection with Braun's anastomosis. Histopathological examination revealed glomus tumor tissue. Literature data on the glomus tumor of the stomach are presented.

The hallmark of severe acute pancreatitis (SAP) is massive acinar cell death by necrosis. However, programmed, apoptotic acinar cell death has also been observed. Little is known about the dynamics, localization, and inductive factors of acinar cell apoptosis in SAP. We therefore induced SAP in rats by retrograde infusion of 3% sodium taurocholate. Starting as early as 5 minutes after taurocholate administration, small scattered groups of acinar cells showed zymogen degranulation, loss of cell polarity, cytoplasmic microvacuolization, and nuclear shrinkage, but no DNA degradation, thus featuring necrosis. The areas of necrotic acini extended at later time points giving rise to larger areas of complete parenchymal breakdown after 6 hours. Parenchymal degradation was paralleled by neutrophil infiltration and significant tumor necrosis factor (TNF)-alpha mRNA up-regulation. Up to the 12-hour interval, apoptotic acinar cells detected by TUNEL were as rare as in healthy pancreata. At 24 hours, however, the acinar apoptotic rate in nonnecrotic parenchyma had dramatically increased. Pretreatment of rats with anti-ICAM-1 antibody prior to pancreatitis induction led to a significant reduction of neutrophil infiltration along with decreased TNF-alpha mRNA expression throughout the 24-hour observation period without affecting the presence and dynamics of necrosis. However, anti-ICAM-1 pretreatment decreased the extent of acinar cell damage by necrosis and extensively suppressed acinar cell apoptosis. We conclude that taurocholate induces two sequential patterns of acinar cell death in terms of very early necrosis followed by late apoptosis during the postacute phase of SAP. The progression of necrosis and the late apoptotic acinar cell death seem to be influenced by the local presence of neutrophils via a TNF-alpha-dependent mechanism. In addition to augmenting necrosis, neutrophils might have an apoptosis-inducing potential in SAP.