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Inflammatory Response After Total Pancreatectomy and Islet Autotransplantation
Inflammatory Response After Total Pancreatectomy and Islet Autotransplantation J.E. Davies, S.A. White, H.A. Clayton, S.M. Swift, and A.R. Dennison
A
FTER total pancreatectomy (TP) and islet autotransplantation (AT) over 50% of patients still have the need for exogenous insulin at 1 year.1 Most islet AT are intraportal; however, this site could be potentially hostile, generating a non-specific inflammatory response in the immediate postoperative period. The liver is host to a variety of immunocompetent cells such as Ku ¨pffer cells that can phagocytose unwanted particulate material and release damaging cytokines (eg, interleukins) that are known to be damaging to islets.2,3 The latter observations taken together with TP for chronic pancreatitis have the potential to generate a complex inflammatory response inducing islet damage after AT. The aim of this study was to assess the systemic release of IL-6 TNF-a and C-reactive protein (CRP) after TP and intraportal islet AT. METHOD Seven patients underwent a pylorus preserving total pancreatectomy with or without (controls) simultaneous intraportal islet AT. Blood samples were taken preoperatively and postoperatively at the time intervals 6, 12, 24 hours and then at days 3, 5, 7 and 14. After centrifugation (3500 g for 10 min) the serum was divided into aliquots and immediately snap frozen in liquid nitrogen and stored at 270°C for later analysis. Cytokines were measured by enzyme amplified immunoassays (Medgenix, Life Screen, Herts, UK) and CRP was measured by latex enhanced turbidometry.
RESULTS
All results are expressed as mean values unless otherwise stated. Overall, four patients (4F; median, 40 years received an islet AT and three further patients (2M, 1F; median, 42 years) having TP alone. The duration of surgery did not significantly differ between either group (449 minutes versus 365 minutes), although those having an islet AT did have a slightly longer procedure. All patients had a peak rise in IL-6 at 6 hours after the procedure, being lower in those having TP alone (122 pg/dL versus 181 pg/dL). Those patients having an islet AT also showed a further peak at 7 days (38 pg/dL) thought to be because of one patient developing a chest infection. In
© 1998 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010 Transplantation Proceedings, 30, 307 (1998)
contrast, CRP peaked in both groups at 24 hours (17.5 mg/dL versus 15.05 mg/dL) with levels being slightly higher in those receiving an islet AT. Lastly, TNF-a peaked at 6 hours (48.9 pg/mL) in those having an islet AT but had rapidly fallen by 12 hours (7.23 pg/mL). Interestingly, patients having TP alone had raised preoperative levels of TNF-a (18.17 pg/mL versus 4.4 pg/mL), decreasing to 5.82 pg/mL by 6 hours. There was also a further peak at 1 week post-op: 12.84 pg/mL versus 9.53 pg/mL. CONCLUSION
The systemic release of CRP and IL-6 were not different between the two groups. There was a 10-fold difference in the levels of TNF-a at 6 hours post-op in those having and islet AT but were elevated preoperatively in those having a TP alone. The latter finding can probably be explained by the relapsing clinical course in these patients and the relatively small sample size. Despite supportive laboratory data (eg, hyperamylasaemia) patients have periods of quiescence and active pancreatitis, thus partly explaining the preoperative difference. The higher levels of TNF-a at 6 hours suggest that an islet AT (with contaminating exocrine tissue) is a greater insult than PT alone, although IL-6 and CRP are raised TNF-a remains relatively unchanged compared with the background levels consequent upon pancreatitis in those patients not receiving an islet AT. REFERENCES 1. International Islet Transplant Registry Report: 6:1, 1996 2. Vara E, Arias-Diaz C, Garcia C, et al: Pancreas 9:316, 1994 3. Vara E, Tamarit-Rodriguez J: Biochem J 278:243, 1991 From the Departments of Surgery, Leicester General Hospital (J.E.D., S.A.W., A.R.D.), and The University of Leicester (H.A.C., S.M.S.), Leicester, United Kingdom. Address reprint requests to Dr S.A. White, University of Leicester, Department of Surgery, CSB, PO Box 65, Leicester LE2 7LX, UK.
0041-1345/98/$19.00 PII S0041-1345(97)01280-3 307
A
FTER total pancreatectomy (TP) and islet autotransplantation (AT) over 50% of patients still have the need for exogenous insulin at 1 year.1 Most islet AT are intraportal; however, this site could be potentially hostile, generating a non-specific inflammatory response in the immediate postoperative period. The liver is host to a variety of immunocompetent cells such as Ku ¨pffer cells that can phagocytose unwanted particulate material and release damaging cytokines (eg, interleukins) that are known to be damaging to islets.2,3 The latter observations taken together with TP for chronic pancreatitis have the potential to generate a complex inflammatory response inducing islet damage after AT. The aim of this study was to assess the systemic release of IL-6 TNF-a and C-reactive protein (CRP) after TP and intraportal islet AT. METHOD Seven patients underwent a pylorus preserving total pancreatectomy with or without (controls) simultaneous intraportal islet AT. Blood samples were taken preoperatively and postoperatively at the time intervals 6, 12, 24 hours and then at days 3, 5, 7 and 14. After centrifugation (3500 g for 10 min) the serum was divided into aliquots and immediately snap frozen in liquid nitrogen and stored at 270°C for later analysis. Cytokines were measured by enzyme amplified immunoassays (Medgenix, Life Screen, Herts, UK) and CRP was measured by latex enhanced turbidometry.
RESULTS
All results are expressed as mean values unless otherwise stated. Overall, four patients (4F; median, 40 years received an islet AT and three further patients (2M, 1F; median, 42 years) having TP alone. The duration of surgery did not significantly differ between either group (449 minutes versus 365 minutes), although those having an islet AT did have a slightly longer procedure. All patients had a peak rise in IL-6 at 6 hours after the procedure, being lower in those having TP alone (122 pg/dL versus 181 pg/dL). Those patients having an islet AT also showed a further peak at 7 days (38 pg/dL) thought to be because of one patient developing a chest infection. In
© 1998 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010 Transplantation Proceedings, 30, 307 (1998)
contrast, CRP peaked in both groups at 24 hours (17.5 mg/dL versus 15.05 mg/dL) with levels being slightly higher in those receiving an islet AT. Lastly, TNF-a peaked at 6 hours (48.9 pg/mL) in those having an islet AT but had rapidly fallen by 12 hours (7.23 pg/mL). Interestingly, patients having TP alone had raised preoperative levels of TNF-a (18.17 pg/mL versus 4.4 pg/mL), decreasing to 5.82 pg/mL by 6 hours. There was also a further peak at 1 week post-op: 12.84 pg/mL versus 9.53 pg/mL. CONCLUSION
The systemic release of CRP and IL-6 were not different between the two groups. There was a 10-fold difference in the levels of TNF-a at 6 hours post-op in those having and islet AT but were elevated preoperatively in those having a TP alone. The latter finding can probably be explained by the relapsing clinical course in these patients and the relatively small sample size. Despite supportive laboratory data (eg, hyperamylasaemia) patients have periods of quiescence and active pancreatitis, thus partly explaining the preoperative difference. The higher levels of TNF-a at 6 hours suggest that an islet AT (with contaminating exocrine tissue) is a greater insult than PT alone, although IL-6 and CRP are raised TNF-a remains relatively unchanged compared with the background levels consequent upon pancreatitis in those patients not receiving an islet AT. REFERENCES 1. International Islet Transplant Registry Report: 6:1, 1996 2. Vara E, Arias-Diaz C, Garcia C, et al: Pancreas 9:316, 1994 3. Vara E, Tamarit-Rodriguez J: Biochem J 278:243, 1991 From the Departments of Surgery, Leicester General Hospital (J.E.D., S.A.W., A.R.D.), and The University of Leicester (H.A.C., S.M.S.), Leicester, United Kingdom. Address reprint requests to Dr S.A. White, University of Leicester, Department of Surgery, CSB, PO Box 65, Leicester LE2 7LX, UK.
0041-1345/98/$19.00 PII S0041-1345(97)01280-3 307