The first histological demonstration of pancreatic oxidative stress in human acute pancreatitis

Necrotizing acute pancreatitis is associated with an inflammatory explosion involving numerous proinflammatory mediator cascades and oxidative stress. Acinar oxygen free radical production aggravates pancreatic tissue damage, and promotes cellular adhesion molecule upregulation resulting in leukocyt e adherence and activation. The cerium capture oxygen free radical histoche mistry combined with reflectance confocal laser scanning microscopy allows the "in situ" histological demonstration of oxygen free radical formation i n Eve tissues. Here we present a case report, where oxidative stress is dem onstrated on a histological level for the first time in human acute pancrea titis. A 44-year-old male patient suffering from acute exacerbation of his chronic pancreatitis developed a pancreato-pleural fistula with amylase-rich left pleural exudate causing respiratory compromise. Subsequent to an urgent tho racic decompression a distal pancreatectomy and splenectomy was performed w ith the closure of abdomino-thoracic fistula. The postoperative course was uneventful, except for a transient pancreatico-cutaneous fistula, which hea led after conservative treatment. To carry out cerium capture oxygen free radical histochemistry the resected pancreas specimen was readily perfused with cerium-chloride solution throu gh the arteries on the resection surface. Frozen sections were cut, E-, P-s electin, ICAM and VCAM were labeled by immunofluorescence. The tumor-free m argin of an identically treated pancreas carcinoma specimen served as a con trol. Intrapancreatic oxidative stress and cellular adhesion molecule expre ssion were detected by confocal laser scanning microscopy. Numerous pancreatic acini and neighboring capillaries showed oxygen free ra dical-derived cerium-perhydroxide depositions corresponding to strong local oxidative stress. Acinar cytoplasmic reflectance signals suggested xanthin e-oxidase as a source of oxygen fi-ee radicals. These areas presented consi derably increased endothelial P-selectin expression with adherent, oxygen f ree radical-producing polymorphonuclear leukocytes displaying pericellular cerium-reflectance. Modest ICAM upregulation was noted, E-selectin and VCAM expression was negligible. The control pancreas specimen showed minimal ox idative stress with weak, focal P-selectin expression. The development of deleterious pancreatic oxidative stress was based on ind irect evidence in human acute pancreatitis. To the best of our knowledge th is is the first report demonstrating persistent intrapancreatic oxidative s tress histologically in human acute pancreatitis. We have noted P-selectin overexpression with a preponderance in the areas of acinar oxidative stress .