Small-Bowel Allograft Biopsies in the Management of Small-Intestinal and Multivisceral Transplant Recipients: Histopathologic Review and Clinical Correlations

Abstract

Context.—Intestinal transplant has become a standard treatment option in the management of patients with irreversible intestinal failure. The histologic evaluation of small-bowel allograft biopsy specimens plays a central role in assessing the integrity of the graft. It is essential for the management of acute cellular and chronic rejection; detection of infections, particularly with respect to specific viruses (cytomegalovirus, adenovirus, Epstein-Barr virus); and immunosuppression-related lymphoproliferative disease. Objective.—To provide a comprehensive review of the literature and illustrate key histologic findings in small-bowel biopsy specimen evaluation of patients with small-bowel or multivisceral transplants. Data Sources.—Literature review using PubMed (US National Library of Medicine) and data obtained from national and international transplant registries in addition to case material at Columbia University, Presbyterian Hospital, and Mount Sinai Medical Center, New York, New York. Conclusions.—Key to the success of small-bowel transplantation and multivisceral transplantation are the close monitoring and appropriate clinical management of patients in the posttransplant period, requiring coordinated input from all members of the transplant team with the integration of clinical, laboratory, and histopathologic parameters.

Immunosuppressive therapies after intestinal transplant modulate the expression of Th1 signature genes during acute cellular rejection. Implications in the search for rejection biomarkers

“…Mild rejection or grade one is characterized by a patchy mild increase in lamina propria inflammation with increased crypt apoptosis, usually more than six apoptotic bodies in 10 consecutive crypts. Even though crypt apoptosis is the most important feature for diagnosis of rejection, increased number of apoptotic bodies may be noted in other inflammatory and infection processes such as viral enteritis (4). Therefore, the treatment of rejection must be indicated after an accurate differential diagnosis is made.…”

“…The diagnosis of ACR is based on endoscopy, histopathological analysis of graft biopsies, and presence of clinical symptoms. As most ITx programs have established follow-up programs based on this strategy, important experience has been gained using this approach (3,4). However, additional tools to help in the diagnostic procedure are awaited due to the complexity of the differential diagnosis and the limitations of endoscopy procedures to access to the full surface of the total graft, because rejection process can show heterogeneous presentation at different intestinal segments (5).…”

Macrochimerism in Intestinal Transplantation: Association With Lower Rejection Rates and Multivisceral Transplants, Without GVHD

“…Protocol biopsies were usually performed 2 times per week for the first month, 1 time per week for the following 2 months, and once a month until one year post-transplant. The pathologic scoring scheme used to grade acute cellular rejection at our institution relies mostly on the apoptotic body count, as previously reported (22)f. Antibody-mediated rejection (AMR) was characterized by the following features: presence of diffuse C4d capillary staining in the lamina propria, associated with vascular changes and circulating DSA. Mixed rejection referred to the co-existence of ACR and AMR.…”

Choice of Allograft in Patients Requiring Intestinal Transplantation: A Critical Review

“…The intestinal allograft is highly immunogenic and chimeric, containing a large amount of lymphoid tissue (gut-associated lymphoid tissue) with the genotype of the epithelial cells remaining mainly that of the donor [2, 35, 43]. The outcomes of IITx are thus marked by high rates of ACR [35].…”