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]i elevation and following ACh removal there was a normal and rapid recovery to a low resting level. The oxidative metabolite acetaldehyde (up to 5 mM) had no effect, whereas the nonoxidative unsaturated metabolite palmitoleic acid ethyl ester (10 -100 M, added on top of 850 mM ethanol) induced sustained, concentration-dependent increases in [Ca 2؉ ]i that were acutely dependent on external Ca 2؉ and caused cell death. These actions were shared by the unsaturated metabolite arachidonic acid ethyl ester, the saturated equivalents palmitic and arachidic acid ethyl esters, and the fatty acid palmitoleic acid. In the absence of external Ca 2؉ , releasing all Ca 2؉ from the endoplasmic reticulum by ACh (10 M) or the specific Ca 2؉ pump inhibitor thapsigargin (2 M) prevented such Ca 2؉ signal generation. We conclude that nonoxidative fatty acid metabolites, rather than ethanol itself, are responsible for the marked elevations of [Ca 2؉ ]i that mediate toxicity in the pancreatic acinar cell and that these compounds act primarily by releasing Ca 2؉ from the endoplasmic reticulum.

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Our results indicate that cases with microscopic tumour involvement within 1 mm of a resection margin should be considered synonymous with incomplete excision for resected pancreatic cancer.

A greater understanding of the natural history of acute pancreatitis combined with greatly improved radiological imaging has led to improvement in the hospital mortality from acute pancreatitis, from around 25–30% to 6–10% in the past 30 years. Moreover, it is now recognised that the first phase of severe acute phase pancreatitis is a systemic inflammatory response syndrome (SIRS), during which multiple organ failure and death often supervene. Survival into the second phase may be accompanied by local complications, such as infected pancreatic necrosis, which may be prevented by prophylactic antibiotics and treated by judicious surgery. Intensive care unit costs can be substantial, but might be justified because of the excellent quality of life of survivors. Reduction in multiple organ failure by agents such as lexipafant, an antagonist of platelet activating factor (PAF) (which plays a critical role in generating the SIRS), may contribute to intensive care unit cost containment, as well as reducing the incidence of local complications and deaths from acute pancreatitis. A further improvement in the human and financial costs also requires the centralisation of the management of patients with severe acute pancreatitis, to single hospital units whose concentrated expertise equips them to intervene most effectively in what is still recognised as a highly complex disease.

R1-direct resections were associated with significantly reduced overall and recurrence-free survival following pancreatic cancer resection. Resection margin involvement was also associated with an increased risk for local recurrence.

Introduction: Open surgery for pancreatic necrosis is associated with considerable morbidity and mortality. We report the results of a recently developed minimally invasive technique that we adopted in 1998. Methods: A descriptive explanation of the approach is given together with the results of a retrospective analysis of patients who underwent a minimally invasive retroperitoneal pancreatic necrosectomy (MIRP) between August 1998 and April 2002. Patients: There were 24 patients with a median (range) age of 61 (29–75) years. The initial median (range) APACHE II score was 8 (2–21). All patients had infected pancreatic necrosis with at least 50% pancreatic necrosis. In three patients it was not possible to complete the first MIRP because of technical reasons. Results: A total of 88 procedures were performed with a median (range) of 4 (0–8) per patient. Twenty-one (88%) patients developed 36 complications during the course of their illness. Five patients required an additional open procedure: 2 for subsequent distant collections, 2 for bleeding and 1 for persisting sepsis and a distant abscess. Six (25%) patients who had MIRP died. The median (range) post-operative hospital stay was 51 (5–200) days. Conclusions: MIRP is a new technique that has shown promising results, and could be preferable to open pancreatic necrosectomy in selected patients. However, unresolved issues remain to be overcome and the exact role of MIRP in the management of pancreatic necrosis has yet to be defined.