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Objective: Multiple organ failure because of systemic inflammatory response in the early phase and sepsis in the late phase is the main contributor to high mortality in severe acute pancreatitis (SAP). High-mobility group box chromosomal protein 1 (HMGB1) was recently identified as a potent proinflammatory mediator and increases in various pathological conditions such as sepsis. The aim of this study was to investigate contributions of HMGB1 in SAP., Methods: We measured serum HMGB1 concentrations by an enzyme-linked immunosorbent assay in 45 patients with SAP at the time of admission. Furthermore, relationship between their serum HMGB1 levels and clinical factors was analyzed., Results: The mean value of serum HMGB1 levels was significantly higher in patients with SAP (5.4 +/- 1.3 ng/mL) than that in healthy volunteers (1.7 +/- 0.3 ng/mL). Serum HMGB1 levels were significantly positively correlated with the Japanese severity score and Glasgow score. Serum HMGB1 levels were significantly positively correlated with lactate dehydrogenase, C-reactive protein, and total bilirubin. The HMGB1 levels were higher in patients with organ dysfunction and infection during the clinical course. The HMGB1 levels in nonsurvivors were higher than those in survivors. Serum HMGB1 levels gradually declined after the admission., Conclusions: Serum HMGB1 levels were significantly increased in patients with SAP and were correlated with disease severity. These results suggest that HMGB1 may act as a key mediator for inflammation and organ failure in SAP.

Background: The shortage of cadaveric donors is a problem in islet transplantation, and recent improvements in this field have led to renewed interest in the use of nonheartbeating (NHB) donors. NHB donor pancreata that could provide a significant source for islet transplantation are associated with warm ischemic injury. We tested whether the two-layer method (TL) could improve islet yield and function from damaged pancreata after warm ischemia (WI)., Methods: Lewis rats were divided into six groups. In groups 1 to 3, rats were subjected to 0, 30, and 45 minutes of WI, respectively. Islets were isolated immediately (subgroup a) or after 3-hour preservation with TL (subgroup b). Isolated islets were assessed in terms of islet yield and in vivo function. We also assessed the pancreatic tissue ATP concentration before isolation and distended pancreata morphologically after chemical digestion by H&E staining., Results: Islet yield decreased significantly after 30 minutes of WI in group 2a, whereas TL preservation doubled this decreased yield in group 2b. Forty-five minutes of WI resulted in nearly no islet yield in both groups 3a and 3b. The success rates of transplantation in groups 1a, 1b, 2a, and 2b were 100%, 100%, 0%, and 75%, respectively. Increased tissue ATP levels and alleviation of morphological islet damage were observed in group 2b., Conclusions: These results demonstrated that pancreata damaged from 30-minute WI were restored by 3-hour TL preservation. TL may allow the selective use of NHB donors as an alternative source for islet transplantation.

Background: Although the outcome of islet transplantation has improved, there remains a major obstacle in isolating viable islets from prolonged preserved pancreas. We previously reported that the two-layer cold storage method (TLM) improved the yield and in vitro function. In this study, we performed in vivo accurate functional analyses of islets from TLM-preserved pancreas and investigated pancreatic duct cell viability, which may critically affect islet isolation., Methods: Rat islets isolated from fresh pancreas (group 1), after preservation in the University of Wisconsin (UW) solution (group 2) or by the TLM (group 3), were examined by assessing islet yields, stimulation indices, cure rates after transplantation to diabetic nude mice, and trypan blue uptake of pancreatic duct cells., Results: TLM significantly improved the islet yield compared with UW cold storage. The cure rates after transplantation were 100%, 0%, and 80% for groups 1, 2, and 3, respectively. This indicates that islet viability was well maintained even after 24 hr of TLM preservation. The percentages of nonviable duct cells were 4.1%+/-1.9%, 48.3%+/-8.0%, and 26.1%+/-21.4% in groups 1, 2, and 3, respectively, showing that the TLM was superior to UW as seen by this duct cell viability assessment., Conclusions: The TLM used for pancreas preservation before islet isolation results in excellent islet function in addition to improved islet yield comparable to freshly isolated islets. The underlying mechanism may be duct cell viability maintained during TLM preservation. Therefore the TLM is an excellent preservation technique for isolating sufficient numbers of highly viable islets.

Background: With the current shortage of donors, there is a critical need to optimally use "less-than-ideal" donors for pancreas transplantation. Objective and rapid means for assessing graft viability and suitability for transplantation are mandatory. This study examined the possibility of graft viability assessment and posttransplant outcome prediction using (31)P-nuclear magnetic resonance (NMR) spectroscopy combined with the two-layer cold-storage method (TLM)., Methods: Canine pancreas grafts were preserved with TLM for 24 hours after 0, 60, or 120 minutes of warm ischemia (groups 1, 2, or 3, respectively). After preservation, we determined intragraft phosphate metabolites noninvasively using (31)P-NMR spectroscopy. Time required for this assessment was 5 minutes. Because our previous studies demonstrated that all grafts in groups 1 and 2 were successfully transplanted (the viable group), whereas all in group 3 failed to survive (the nonviable group), the possibility of posttransplant outcome prediction was examined on the basis of the comparison between these two groups., Results: The ratios of inorganic phosphate/gamma-adenosine triphosphate (Pi/gamma-ATP) and Pi/beta-ATP reflected the extent of graft damage, and the differences were statistically significant among groups 1, 2, and 3. On the basis of analyses of receiver operator characteristic curves, the optimum cutoff levels between the viable and nonviable groups were 1.6 and 2.2 for Pi/gammaATP and Pi/betaATP, respectively. The accuracy rates of these ratios were both 83%., Conclusion: (31)P-NMR spectroscopy combined with TLM preservation could provide an objective, rapid, and possibly noninvasive means to assess pancreas graft viability and to determine suitability of damaged pancreata for organ transplantation.

Background: The purpose of this study is to examine the possibility of a long-term preservation of the ischemically damaged intestine by the cavitary two-layer method (TLM) in canine small intestinal transplantation., Methods: The grafts were allotransplanted without preservation immediately (group 1) or after 30 minutes of warm ischemia (group 2). The ischemically damaged grafts were also allotransplanted after cold preservation for 24 hours in University of Wisconsin (UW) solution (group 3) or the cavitary TLM (group 4). Seven-day survivals, tissue adenosine triphosphate (ATP) concentrations, absorption tests, and histopathology were examined., Results: seven-day survivals in groups 1, 2, 3, and 4 were 8 of 8, 6 of 8, 0 of 8, and 6 of 8, respectively. In group 4, significant recovery of ATP tissue level was seen after preservation compared with group 3, and absorption function and regeneration of the graft mucosa recovered at day 14., Conclusions: Ischemically damaged canine small intestine could be preserved for 24 hours by the cavitary TLM.