Clinical subtypes of Crohn's disease according to surgical outcome.

Patients with Crohn's disease are typically classified into perforator or nonperforator groups. The perforator group includes those who present with acute perforation, fistulas, or abscess formation. The nonperforator group presents with stricture, obstruction, or unresponsiveness to medical therapy. Our purpose was to investigate whether perianal disease constitutes a separate predictor of surgical outcome. The form of presentation was classified as perforator, nonperforator, or perianal disease in 91 patients undergoing 232 operations for Crohn's disease. Those with perforating complications presented with the highest Crohn's Disease Activity Index, followed by those with nonperforating complications, and then the perianal disease group. However, the perianal disease group appeared to have the most rapid rate of recurrence and subsequent surgery, followed next by the perforator, and then the nonperforator group. Recurrence rate and subsequent operation intervals for the perforator group appeared to lengthen when those patients were treated with steroids and/or immunosuppressants, as compared to nonsteroidal and/or antimicrobial agents. Recurrence rate and subsequent operation intervals appeared to lengthen for the nonperforator and perianal disease groups when they were treated with nonsteroidal and/or antimicrobial therapy, as compared to steroids and/or immunosuppressants. Our data indicate that perianal disease, as a form of presentation of Crohn's disease, has independent predictive value, although this is not accurately reflected by the Crohn's Disease Activity Index.

Localization of thrombospondin-1 and its cysteine-serine-valine-threonine-cysteine-glycine receptor in colonic anastomotic healing tissue.

Thrombospondin-1 (TSP-1) is a matrix protein implicated in mechanisms of wound healing. TSP-1 contains the sequence cysteine-serine-valine-threonine-cysteine-glycine (CSVTCG) that has been shown to function primarily as a cell adhesion domain. Our laboratory has isolated a novel receptor specific for the CSVTCG adhesive domain of TSP-1. Immunohistochemical staining techniques and computerized image analysis were used to identify and quantitate TSP-1 and its CSVTCG receptor in surgically created colon anastomotic wounds. Histopathologic and quantitative examination demonstrated increased expression of TSP-1 and its CSVTCG receptor in areas of wound healing. These findings suggest a role for TSP-1 and its CSVTCG receptor in wound healing. The control of expression and activity of these molecules may eventually be the basis for the development of wound healing agents that could significantly reduce the morbidity from surgical intervention.

Temporal expression of TGF-beta1, EGF, and PDGF-BB in a model of colonic wound healing.

BACKGROUND: Dehiscence of colonic anastomoses is a multifactorial phenomenon. One mechanism by which this can occur is a deficiency of colonic submucosal collagen. Peptide growth factors (PGFs) have been shown to play a role in the synthesis, deposition, and maturation of collagen. Specifically, in tissues other than the colon, the transforming growth factor-beta (TGF-beta1) gene has been shown to be temporally associated with expression of the procollagen gene. This study examines the temporal expression of the TGF-beta1, epidermal growth factor (EGF), and platelet-derived growth factor B (PDGF-BB) genes and their temporal relationship to the expression of the procollagen type 1 (PROC I) gene. MATERIALS AND METHODS: Forty-eight Sprague-Dawley rats underwent transection of the descending colon with primary anastomosis. Perianastomotic colonic tissue was harvested on Day 0 and postoperative days 3, 5, 6, 7, and 14. Colonic tissue was analyzed using semiquantitative reverse transcriptase-polymerase chain reaction and primers specific for the TGF-beta1, EGF, and PDGF-B growth factors. Relative expression ratios of PGFs and PROC I genes were calculated versus a constitutive gene. RESULTS: The data show that although all three of the PGFs genes were expressed in healing postoperative colonic tissue, only TGF-beta1 showed a significant increase in its level of expression versus a constitutive gene from a mean ratio of 0.4 +/- 0. 08 on Day 0 to a mean ratio of 1.9 +/- 0.27 on Day 7 (P < 0.0001 by ANOVA). The PROC I gene also showed a significant increase in expression (P < 0.001 by ANOVA) in the postoperative period which temporally correlated with the increase in the expression of the TGF-beta1 gene (r = 0.89, P < 0.05). CONCLUSIONS: The temporal correlation between an increase in the gene expression of TGF-beta1 and PROC I is initial evidence that that TGF-beta1 plays a significant role in collagen metabolism in a healing colonic anastomosis.

Intravenous butyrate and healing of colonic anastomoses in the rat.

PURPOSE: Intracolonic infusions of short chain fatty acids promote healing of colonic anastomoses. Because the intravenous route may have wider clinical application, we studied the effect of intravenous n-butyrate on the mechanical strength of colonic anastomoses in the rat. METHODS: After placement of an indwelling intravenous catheter, the descending colon was transected and an anastomosis was performed. Rats were then randomized to receive total parenteral nutrition (TPN group; n = 15) or total parenteral nutrition plus 130 mM/l of n-butyrate (TPN+BUT group; n = 13). On the fifth postoperative day, bursting pressure and bowel wall tension of the anastomoses were measured in situ. Anastomotic tissues were analyzed for hydroxyproline. RESULTS: The TPN+BUT group had a significantly higher bursting pressure (107.5 +/- 30.3 vs. 83 +/- 41.0 mmHg; P = 0.04) and bowel wall tension (20.7 +/- 7.6 vs. 14.1 +/- 9.9 Newton; P = 0.03). Tissue hydroxyproline was not different between the two groups (TPN, 45.8 +/- 9.2, and TPN+BUT, 47.9 +/- 2.9 microg/mg tissue nitrogen). CONCLUSIONS: We conclude that intravenous butyrate improves mechanical strength of a colonic anastomosis without a detectable change in total collagen content.