T. Lysyy1, M. Finotti1,2, R. Morotti1, A. S. Munoz-Abraham1, A. Bertacco2, R. Agarwal1, C. Ibarra1, R. Patron1, A. Alkukhun1, F. D’Amico1,2, M. Rodriguez-Davalos1, D. Mulligan1, J. Geibel1 1Yale University School Of Medicine,Surgery,New Haven, CT, USA 2University Of Padua,Transplantation And Heptobiliary/Surgery,Padua, PADUA, Italy
Introduction: The human small intestine is the most ischemia-sensitive organ among all transplanted abdominal organs. Intestinal transplantation (IT) is an effective alternative for total parenteral nutrition in patients with short-bowel syndrome or intestinal failure. Postoperative complications of IT (including graft failure, acute rejection, and necrosis) are correlated to poor preservation and prolonged ischemia time. In this study, we evaluated the sensitivity of human small intestinal grafts to ischemic injury in two different hypothermic preservation conditions, and compared the extent of ischemic damage in both proximal (jejunum) and distal (ileum) segments.
Methods: Eighteen human small intestines were procured: 14 grafts were obtained on site with cold ischemia time (CIT) range of 1-4 hours (avg. 2.03 hrs), and 4 were shipped to our institution with CIT range of 5-9 hours (avg. 7.56 hrs). Histological samples were collected from jejunum and ileum intestinal segments at different time points (2 samples per time point from each segment, n=208 samples). The first set of samples was obtained at the time of procurement/organ delivery (T0) (baseline histological assessment). A second set was obtained at T0 with samples stored at 4oC for mean 8.6 hours (T8). A third set was obtained after mean 8.6 hours of continuous hypothermic perfusion using an intestinal perfusion unit (IPU) (PT8). All samples were fixed with 10% formalin prior to a blinded histological evaluation. Samples were scored using the Park/Chiu system. Scores were analyzed with Graph Pad Prism 6 for each group.
Results:In the group with CIT 1-4 hrs at T0, there was no histological score difference between the jejunum and ileum (mean score in proximal samples 0.928 vs distal 0.961). However, at T8 (mean score in proximal was 2.10 vs distal 1.39, (p<0.0005)) and PT8 (mean proximal 1.89 vs distal 1.25, (p<0.0005)), there is a statistically significant difference in the ischemic scores of the jejunum and ileum. In the second group with CIT 5-9 hrs the mean ischemic scores at T0 were 2.38 in jejunum and 1 in ileum (p<0.0232). At T8, the mean scores were 3 for jejunum and 3.75 for ileum, with no statistical difference (p>0.05). Similarly, at PT8 (mean ischemic scores: proximal 3.12 vs distal 3.87), there was no difference in the degree of ischemia between the two segments, (p>0.05).
Conclusion:The proximal segment (jejunum) of the human intestine is more susceptible to ischemia than the distal segment (ileum). Prolonged CIT (5-9 hrs) increases the degree of ischemic damage, affecting the jejunum more than ileum. The early use of the intestinal perfusion unit after procurement (<5 hours) appeared to reduce ischemic injury in the jejunum compared to static cold storage. Furthermore, selective transplantation of the more distal segment of the small intestine (ileum) could reduce ischemia-related postoperative complications and improve clinical outcomes and patient survival.