Chronic Rejection of Small Bowel Grafts: Pediatric and Adult Study of Risk Factors and Morphologic Progression

Abstract

One hundred and seventy-two patients underwent small bowel transplantation at Children's Hospital of Pittsburgh and University of Pittsburgh Medical Center between May 1990 and August 2001. Thirty-four patients had complete or partial resection of their primary graft and in 15, histologic features of chronic rejection were present in the resected small bowel. This is a descriptive and correlative study of the demographic, perioperative, and histologic features associated with progression to intestinal graft failure. Variable features associated with an increased risk of chronic rejection included acute rejection within the 1st month, increased number and higher grade of acute rejection episodes, isolated small bowel grafts rather than small bowel-liver grafts, older recipient age, non-Caucasian race, and Caucasian to non-Caucasian transplant. The mucosal biopsies showed predictive changes many months before the grafts were excised. The mucosal biopsy diagnosis of chronic vascular rejection can be difficult because the affected vessels, the distal branches of the mesenteric arteries, and the larger arteries of the subserosa and submucosa are not routinely sampled. The possibility of underlying arteriopathy, however, can be inferred in some instances from the presence of secondary mucosal changes in the small bowel biopsies though the "early" changes lack specificity. It is the progression of biopsy findings over time that is predictive of outcome. It is important to recognize the persistence of "late" mucosal changes of chronic rejection so that patients are not subjected to increased immune suppression when it is unlikely to be of significant benefit.

Intestinal Regeneration, Residual Function and Immunological Priming Following Rescue Therapy After Rat Small Bowel Transplantation

“…In clinical transplantation, occurrence of an ACR episode within 30 days posttransplant and a higher number of ACR episodes have been associated with progression to chronic rejection (14). Our findings clearly demonstrate increased graft fibrosis after the treatment and recovery from acute rejection, even after only one episode of rejection in this experimental setting.…”

“…IL-6 mRNA elevation) and were accompanied with an upregulation of the fibrogenic marker VEGF. As chronic rejection of the intestine is mainly characterized by graft fibrosis, intimal hyperplasia of submucosal arteries and chronic ulcers with neutrophil-rich exudate and granulation tissue (14), it could be speculated that this increase in Sirius Red-positive areas along with the mentioned histological changes does indeed represent early stage fibrotic changes.…”

Glucagon-like peptide-2 acutely increases proximal small intestinal blood flow in TPN-fed neonatal piglets

“…These findings may be clinically relevant for the prevention and treatment of intestinal dysfunction in infants, especially those supported by TPN, to maintain mucosal growth and function. These results also may be clinically relevant by serving to augment blood flow and minimize tissue ischemia in chronic rejection in small boweltransplanted patients and during pancreatitis (21,23).…”

Current Status of Intestinal Failure and Intestinal Transplantation

“…The pathology of chronic rejection is intimal hyperplasia and obliterative arteriopathy in the submucosal layers. Endoscopic biopsies may show mucosal and submucosal fibrosis and atrophy, distorted villi, crypt damage, and occasionally arteriopathy of small arterioles [48]. However, a full thickness biopsy is needed to confirm this diagnosis, which is manifested by atherosclerotic-type lesions with eccentric intimal hyperplasia and concentric fibrous intimal thickening in the large and medium-size arteries.…”