- Email: [email protected]
A systematic review of the extra-pancreatic infectious complications in acute pancreatitis
Abstracts / Pancreatology 14 (2014) S1eS129
O-47. A systematic review of the extra-pancreatic infectious complications in acute pancreatitis Lisa Brown, Todd Hore, Anthony Phillips, John Windsor, Max Petrov University of Auckland, New Zealand Background: Extra-pancreatic infectious complications (EIC) in patients with AP has been shown to influence morbidity and mortality. Further, on review of the bacteriology of infection of necrosis, close to half of the bacteria are not of enteric origin. This raises the possibility of systemic infection as the origin of infection. Aims: The aim of this systematic review was to assess the incidence of EIC in patients with AP, its potential impace and the timing of diagnosis of the infection. Patients & methods: Search performed on Ovid MEDLINE (1946 to present), Embase (1980 to present) and Cochrane Libraries. Search terms used 'Pancreatitis' AND 'Infection' AND ('Complication' OR 'Outcome'), using PRISMA guidelines. Results: A total of 1041 papers were screened, with 19 studies included in the final analysis. The studies consisted of two prospective non-RCT's and 17 RCTs. A total number of 1,741 patients with AP were included, with a combined mortality of 10%. The total prevalence of extra-pancreatic inffection was 26%, with pneumonia (and other respiratory inctions) the most common at 9.2%. Two studies (n¼781 patients) reported diagnosis of EIC at a median of 7.5 days. Compared with pancreatic infection, reported in four studies (n¼843 patients) occuring later at a median of 23.4 days. Conclusion: Extra-pancreatic infections is a common complication in patients with AP with respiratory infection the most prevalent. EICs are most likely to occur early in the cours of AP. Recognition should be made of the occurrence of EIC in AP, with prevention/treatment modalities administered early to curb morbidity and mortality.
O-48. Disruption of fractalkine/CX3CR1 signaling attenuates acute pancreatitis and pancreatic pain Jan DHaese a, Tom D. D'Haese a, Hamza Sezgin a, Timo Kehl a, Ihsan Ekin Demir a, Frank Bergmann b, Helmut Friess a, Güralp O. Ceyhan a a Department of Surgery, Klinikum Rechts der Isar, Technische €t München, Munich, Germany, Germany Universita b Institute of Pathology, University of Heidelberg, Heidelberg, Germany, Germany
Background: Acute pancreatitis (AP) is characterized by vast inflammatory cell infiltration and severe abdominal pain. Fractalkine is a chemokine that chemoattracts inflammatory cells through its highly selective receptor CX3CR1 and has been suggested to aggravate pancreatic inflammation and pain. Spinal cord microglia express the receptor CX3CR1 and have been shown to modulate pain in chronic pain states. Aims: We aimed to investigate the course of acute cerulein pancreatitis in CX3CR1-/- mice and the potential therapeutic implications of CX3CR1 neutralization. Materials & methods: AP was induced in CX3CR1-knockout and CX3CR1-blocking treated wild-type mice by repetitive intraperitoneal cerulein injections. Hyperalgesia was assessed by systematic behavioral observation and measurement of abdominal mechanical sensitivity. Pancreatic and spinal cord tissue was harvested after sacrifice for further analyses. Results: Histological severity of AP in CX3CR1-knockout mice vs wildtype controls was comparable. CX3CR1-blocking treated mice however showed an attenuated AP with significantly less pancreatic inflammatory cell infiltration. Both knockout and treated mice showed significantly less
S17
pain related behaviour (p < 0.0001) with a clear dose-response correlation. Intrapancreatic IL6 and MCP-1 levels were lower in treated mice when compared to their controls. On the spinal cord level, CX3CR1-blocking treated mice showed a dose dependent decrease of microglial activation measured by p-p38 Immunohistochemistry. Conclusion: Fractalkine signaling seems to be crucial in initiating and maintaining pancreatic hyperalgesia in acute pancreatitis, most likely by triggering of the local inflammatory reaction and activating spinal cord microglia via the highly selective receptor CX3CR1. Therefore, these novel findings reveal CX3CR1 as a promising new target for the treatment of acute pancreatitis.
O-49. Acute pancreatic ascites causes mitochondrial dysfunction in endothelial cells Catherine Yang, Kathryn Askelund, Anthony Hickey, Shorena Nachkebia, John Windsor, Anthony Phillips University of Auckland, New Zealand Background: Early organ-specific mitochondrial dysfunction has been demonstrated in experimental models of acute pancreatitis (AP). This dysfunction has been implicated in mediating severity of AP but the mechanism for this is unclear. There is lack of consensus in the literature about merits of draining pancreatic ascites. Aims: The aim of this study was to elucidate the role of pancreatic ascites in mitochondrial dysfunction and severity of AP. Materials & methods: Severe taurocholate pancreatitis was induced in 16 male Wistar rats. Pancreatic ascites was pooled and filtered. Severity of AP was verified serologically and on autopsy. Sterility of ascites confirmed after incubation in media for 24 hours. Ascites and controls were incubated with human microvascular endothelial cells (HMEC-1), for 2 hours (n¼6) of triplicates. Cellular viability was assessed with Prestoblue, mitochondrial membrane potential with JC-1, superoxide production with MitoSox, lactate dehydrogenase, IL-6 and IL-8 levels were also measured. Results: There was a dose response effect. Addition of 5% AP-conditioned ascites to cells caused a 28% decrease in cellular viability (p<0.0001), 2.0 times decrease in the mitochondrial membrane potential ratio (p<0.05), a 463% increase in superoxide production (p<0.05); a trend for increased lactate dehydrogenase and non-significant increases in IL-6 and IL-8 levels. Conclusion: This study found the addition of pancreatic ascites to healthy endothelial cells induced mitochondrial damage similar to that seen in organs with severe AP. This provides a new perspective on the debate regarding peritoneal lavage. Further work to investigate toxic mechanisms of ascites is now warranted.
O-50. A computer-based automated algorithm for assessing acinar cell loss after experimental pancreatitis John Eisses a, Amy Davis b, Akif Tosun c, John Ozolek b, Gustavo Rohde c, Sohail Husain a a
Children's Hospital of Pittsburgh, Gastroenterology, United States Children's Hospital of Pittsburgh, pathology, United States c Carnegie Mellon University, Biomedical engineering, United States b
Background: The change in exocrine mass is an important parameter to follow in experimental models of pancreatic injury and regeneration. However, at present, the quantitative assessment of exocrine content by histology is tedious and operator-dependent, requiring manual assessment of acinar area on serial pancreatic sections.
O-47. A systematic review of the extra-pancreatic infectious complications in acute pancreatitis Lisa Brown, Todd Hore, Anthony Phillips, John Windsor, Max Petrov University of Auckland, New Zealand Background: Extra-pancreatic infectious complications (EIC) in patients with AP has been shown to influence morbidity and mortality. Further, on review of the bacteriology of infection of necrosis, close to half of the bacteria are not of enteric origin. This raises the possibility of systemic infection as the origin of infection. Aims: The aim of this systematic review was to assess the incidence of EIC in patients with AP, its potential impace and the timing of diagnosis of the infection. Patients & methods: Search performed on Ovid MEDLINE (1946 to present), Embase (1980 to present) and Cochrane Libraries. Search terms used 'Pancreatitis' AND 'Infection' AND ('Complication' OR 'Outcome'), using PRISMA guidelines. Results: A total of 1041 papers were screened, with 19 studies included in the final analysis. The studies consisted of two prospective non-RCT's and 17 RCTs. A total number of 1,741 patients with AP were included, with a combined mortality of 10%. The total prevalence of extra-pancreatic inffection was 26%, with pneumonia (and other respiratory inctions) the most common at 9.2%. Two studies (n¼781 patients) reported diagnosis of EIC at a median of 7.5 days. Compared with pancreatic infection, reported in four studies (n¼843 patients) occuring later at a median of 23.4 days. Conclusion: Extra-pancreatic infections is a common complication in patients with AP with respiratory infection the most prevalent. EICs are most likely to occur early in the cours of AP. Recognition should be made of the occurrence of EIC in AP, with prevention/treatment modalities administered early to curb morbidity and mortality.
O-48. Disruption of fractalkine/CX3CR1 signaling attenuates acute pancreatitis and pancreatic pain Jan DHaese a, Tom D. D'Haese a, Hamza Sezgin a, Timo Kehl a, Ihsan Ekin Demir a, Frank Bergmann b, Helmut Friess a, Güralp O. Ceyhan a a Department of Surgery, Klinikum Rechts der Isar, Technische €t München, Munich, Germany, Germany Universita b Institute of Pathology, University of Heidelberg, Heidelberg, Germany, Germany
Background: Acute pancreatitis (AP) is characterized by vast inflammatory cell infiltration and severe abdominal pain. Fractalkine is a chemokine that chemoattracts inflammatory cells through its highly selective receptor CX3CR1 and has been suggested to aggravate pancreatic inflammation and pain. Spinal cord microglia express the receptor CX3CR1 and have been shown to modulate pain in chronic pain states. Aims: We aimed to investigate the course of acute cerulein pancreatitis in CX3CR1-/- mice and the potential therapeutic implications of CX3CR1 neutralization. Materials & methods: AP was induced in CX3CR1-knockout and CX3CR1-blocking treated wild-type mice by repetitive intraperitoneal cerulein injections. Hyperalgesia was assessed by systematic behavioral observation and measurement of abdominal mechanical sensitivity. Pancreatic and spinal cord tissue was harvested after sacrifice for further analyses. Results: Histological severity of AP in CX3CR1-knockout mice vs wildtype controls was comparable. CX3CR1-blocking treated mice however showed an attenuated AP with significantly less pancreatic inflammatory cell infiltration. Both knockout and treated mice showed significantly less
S17
pain related behaviour (p < 0.0001) with a clear dose-response correlation. Intrapancreatic IL6 and MCP-1 levels were lower in treated mice when compared to their controls. On the spinal cord level, CX3CR1-blocking treated mice showed a dose dependent decrease of microglial activation measured by p-p38 Immunohistochemistry. Conclusion: Fractalkine signaling seems to be crucial in initiating and maintaining pancreatic hyperalgesia in acute pancreatitis, most likely by triggering of the local inflammatory reaction and activating spinal cord microglia via the highly selective receptor CX3CR1. Therefore, these novel findings reveal CX3CR1 as a promising new target for the treatment of acute pancreatitis.
O-49. Acute pancreatic ascites causes mitochondrial dysfunction in endothelial cells Catherine Yang, Kathryn Askelund, Anthony Hickey, Shorena Nachkebia, John Windsor, Anthony Phillips University of Auckland, New Zealand Background: Early organ-specific mitochondrial dysfunction has been demonstrated in experimental models of acute pancreatitis (AP). This dysfunction has been implicated in mediating severity of AP but the mechanism for this is unclear. There is lack of consensus in the literature about merits of draining pancreatic ascites. Aims: The aim of this study was to elucidate the role of pancreatic ascites in mitochondrial dysfunction and severity of AP. Materials & methods: Severe taurocholate pancreatitis was induced in 16 male Wistar rats. Pancreatic ascites was pooled and filtered. Severity of AP was verified serologically and on autopsy. Sterility of ascites confirmed after incubation in media for 24 hours. Ascites and controls were incubated with human microvascular endothelial cells (HMEC-1), for 2 hours (n¼6) of triplicates. Cellular viability was assessed with Prestoblue, mitochondrial membrane potential with JC-1, superoxide production with MitoSox, lactate dehydrogenase, IL-6 and IL-8 levels were also measured. Results: There was a dose response effect. Addition of 5% AP-conditioned ascites to cells caused a 28% decrease in cellular viability (p<0.0001), 2.0 times decrease in the mitochondrial membrane potential ratio (p<0.05), a 463% increase in superoxide production (p<0.05); a trend for increased lactate dehydrogenase and non-significant increases in IL-6 and IL-8 levels. Conclusion: This study found the addition of pancreatic ascites to healthy endothelial cells induced mitochondrial damage similar to that seen in organs with severe AP. This provides a new perspective on the debate regarding peritoneal lavage. Further work to investigate toxic mechanisms of ascites is now warranted.
O-50. A computer-based automated algorithm for assessing acinar cell loss after experimental pancreatitis John Eisses a, Amy Davis b, Akif Tosun c, John Ozolek b, Gustavo Rohde c, Sohail Husain a a
Children's Hospital of Pittsburgh, Gastroenterology, United States Children's Hospital of Pittsburgh, pathology, United States c Carnegie Mellon University, Biomedical engineering, United States b
Background: The change in exocrine mass is an important parameter to follow in experimental models of pancreatic injury and regeneration. However, at present, the quantitative assessment of exocrine content by histology is tedious and operator-dependent, requiring manual assessment of acinar area on serial pancreatic sections.