TGF-beta1 and IGF-1 and anastomotic recurrence of Crohn's disease after ileo-colonic resection.
BACKGROUND
After bowel resection, Crohn's disease (CD) recurs frequently in the site of the anastomosis. Alteration of normal healing processes may play a role in this phenomenon. Transforming growth factor beta (TGF-beta) and insulin-like growth factor (IGF-1) are involved in wound healing mechanisms with pro-fibrogenic properties. The aim of this study was to assess the expression of TGF-beta1 and insulin-like growth factor 1 (IGF-1) in the different zones of the bowel wall to understand why side-to-side anastomosis are associated to a lower recurrence rate compared to end-to-end ones.


METHODS
Seventeen patients affected by CD who underwent ileo-colonic resection from 2004 to 2005 were enrolled in this study. Full-thickness tissue samples were obtained from the mesenteric, the lateral, and the anti-mesenteric sides of the macroscopically diseased and healthy ileum for each patient. TGF-beta1 and IGF-1 messenger RNAs (mRNAs) were quantified by real-time polymerase chain reaction. Myeloperoxidase activity and histological disease activity were assessed to quantify the ileal inflammation. Vimentin, desmin, and alpha-smooth muscle actin were stained with immunohistochemistry to assess the fibroblast, smooth muscle cell, and myofibroblasts populations. Comparisons and correlations were carried out with nonparametric tests.


RESULTS
In diseased ileum, TGF-beta1 mRNA transcripts in the antimesenteric side were significantly lower than those of the mesenteric side (p = 0.05), and a significant correlation between TGFbeta-1 levels in diseased bowel and the sampling site was observed (tau = 0.36, p = 0.03). On the contrary, neither the IGF-1 mRNA transcripts nor the distribution of fibroblast, smooth muscle cell, and myofibroblasts populations showed any relation with the sampling site.


CONCLUSIONS
TGF-beta1 mRNA expression was lower in the anti-mesenteric side of the diseased ileum, and this was consistent with the success of side-to-side anastomosis in preventing CD recurrence. Since high expression of TGF-beta1 was associated to early recurrence, it seems rationale to construct the anastomosis on the anti-mesenteric side of the bowel.
Scarpa
Marco
M
Clinica Chirurgica I, Dipartimento di Scienze Chirurgiche e Gastroenterologiche, Policlinico Universitario, Università di Padova, via Giustiniani 2, 35128, Padova, Italy. marcoscarpa73@yahoo.it
Bortolami
Marina
M
Morgan
Susan L
SL
Kotsafti
Andromachi
A
Ruffolo
Cesare
C
D'Incà
Renata
R
Bertin
Eugenia
E
Polese
Lino
L
D'Amico
Davide F
DF
Sturniolo
Giacomo C
GC
Angriman
Imerio
I
D000328:Adult; D000368:Aged; D000714:Anastomosis, Surgical / Q000009:adverse effects; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D003106:Colon / Q000601:surgery*; D003424:Crohn Disease / Q000175:diagnosis / Q000601:surgery*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007082:Ileum / Q000601:surgery*; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D007813:Laparotomy / Q000379:methods; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011336:Probability; D012008:Recurrence; D018570:Risk Assessment; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*; D016896:Treatment Outcome
D015415:Biomarkers; D053773:Transforming Growth Factor beta1; D007334:Insulin-Like Growth Factor I