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ucosal Fibrosis in Intestinal Transplant Biopsies Correlatesositively With the Development of Chronic Rejection
. Tryphonopoulos, D. Weppler, S. Nishida, T. Kato, D. Levi, G. Selvaggi, J. Moon, J.R. Madariaga,. DelaGarza, A. Tzakis, and P. Ruiz
ABSTRACT
Endoscopic biopsies of intestinal allografts are limited to the superficial layers of thebowel. We investigated whether the presence of mucosal fibrosis in graft biopsies wasindicative of chronic allograft rejection. We examined graft biopsies of 182 intestinaltransplant recipients for the presence of mucosal fibrosis. Kaplan-Meier analysis showedthat within 5 years posttransplantation 33% of intestinal transplant patients had graftbiopsies positive for mucosal fibrosis. Although the presence of mucosal fibrosis did notaffect patient or graft survival, patients with this lesion were at higher risk of developing
chronic allograft enteropathy.RP
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NDOSCOPIC BIOPSIES of intestinal allografts arelimited to the superficial layers of the bowel, thus
imiting evaluation for chronic injury.1 The aim of our studyas to investigate whether the presence of mucosal fibrosis
n the graft biopsy was indicative of chronic rejection.
ATERIALS AND METHODS
ndoscopic graft biopsies of patients who had received an intesti-al graft from October 1994 to October 2004 were reviewed for theresence of mucosal fibrosis. Follow-up was until the end ofebruary 2005. Mucosal fibrosis was detected by microscopicxamination of the graft biopsy. Its presence was confirmed by aositive Trichrome stain.
Table 1. Patient Demographics
Group A(mucosal fibrosis)
Group B(no fibrosis) P
39 143ale/female 23/16 74/69 .4dult/pediatric 18/22 52/91 .3ype of graftIntestine 15 42 .3Liver-intestine 4 28 .2Modified multivisceral 6 8 .04Multivisceral 14 65 .3old ischemia time (min) 421 � 14 425 � 8 .8arm ischemia time (min) 39 � 1 41 � 2 .6onor age (y) 13.25 � 2.52 10.41 � 1.12 .3
mecipient age (y) 17.84 � 2.67 15.08 � 1.45 .4
2006 by Elsevier Inc. All rights reserved.60 Park Avenue South, New York, NY 10010-1710
ransplantation Proceedings, 38, 1685–1686 (2006)
ESULTSatients with Mucosal Fibrosis
mong 182 intestinal transplant patients, 39 (group A)howed mucosal fibrosis in their graft biopsies versus 143group B) who did not display this lesion. In group A, theatients including 22 pediatric and 18 adult recipients and6 female and 23 male subjects received isolated intestinaln � 15), liver-intestinal (n � 4), multivisceral (n � 14), or
From the Department of Surgery and Pathology, University ofiami, Miami, Florida, USA.Address reprint requests to Phillip Ruiz, University of Miami,
epartment of Surgery and Pathology, 1611 NW 12th Avenue,MH-Holtz Center #2101, Miami, FL, 33136, USA. E-mail: Pruiz@
ig 1. Kaplan-Meier curve of percentage of patients withoutucosal fibrosis at their graft biopsies.
ed.miami.edu
0041-1345/06/$–see front matterdoi:10.1016/j.transproceed.2006.05.019
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1686 TRYPHONOPOULOS, WEPPLER, NISHIDA ET AL
odified multivisceral grafts (n � 6). There were noignificant differences in the distribution of the types ofransplants between the two groups (Table 1).
Four recipients were transplanted from 1996 to 1997nder immunosuppression with tacrolimus and steroids.he rest of the patients, who were transplanted from998 until 2004, additionally received Zenapax (n � 25)r Campath-1H (n � 10) induction immunosuppression.welve patients transplanted between 1996 and 2000 also
eceived donor bone marrow infusions.Mucosal fibrosis was observed for the first time at 0.7 to
0 (mean: 7.3 � 1.2) months posttransplantation. Thebrosis lesion was mild in the majority of the cases (n � 35)nd moderate in a few (n � 4). Kaplan-Meier analysishowed that 33% of our intestinal transplant patients hadraft biopsies positive for mucosal fibrosis within 5 yearsosttransplantation (Fig 1).There was no significant difference in patient or graft
urvival when the patient displayed mucosal fibrosis (Fig 2).t the end of the follow-up period, 18 of the 39 patients in
roup A are still alive with functioning grafts at 0.02 to 6 yearsmedian 2.7 � 0.63) after the initial graft biopsy was positiveor mucosal fibrosis. The causes of death included chronicejection (n � 2); acute rejection (n � 8); sepsis (n � 6);raft-versus-host disease (n � 1); portal vein thrombosis
ig 2. Patient (A) and graft (B) survival. Group A: patients with pithout mucosal fibrosis.
n � 1); hemolysis (n � 2); and viral pneumonia (n � 1). b
resence of Chronic Rejection in the Explanted Grafts
n group A 13 full-thickness grafts were available for patho-ogical examination after total (n � 11) or partial (n � 2) graftesection. Nine grafts (69.2%) showed changes consistentith chronic rejection that were mild (n � 5) or moderate
n � 2), or severe (n � 2). Among group B, out of the 14xplanted grafts available for pathologic examination, nonead changes consistent with chronic rejection.
ISCUSSION
ucosal fibrosis was present in graft biopsies of about onehird of intestinal transplant patients at 5 years posttrans-lantation. The presence of mucosal fibrosis did not signif-
cantly affect patient or graft survival. Mucosal fibrosisdentified a group of recipients at higher risk for developinghronic allograft enteropathy.1
EFERENCE
1. Perez MT, Garcia M, Weppler D, et al: Temporal relation-hips between acute cellular rejection features and increaseducosal fibrosis in the early post-transplant period of human small
nce of mucosal fibrosis at their graft biopsies; group B: patients
reseowel allografts. Transplantation 73:555, 2002
