Rejection In Small Bowel Transplantation Research Articles

Histologic Analysis of Chronic Rejection in Small Bowel Transplantation

Chronic rejection is a significant barrier to small bowel allograft survival. Although chronic rejection primarily involves vessels of the submucosa, serosa, and mesentery, some mucosal alterations have been suggested to be correlative. We retrospectively investigated explanted small bowel allografts for clinical characteristics and histological alterations in the mucosa, submucosa, and serosa. Crypt epithelial mucin loss, submucosal fibrosis, and length of time to explant were all statistically associated with chronic rejection. Medium-sized and large-sized vessels of the serosa and mesentery preferentially demonstrated histologic changes of chronic rejection. These results further define chronic vascular rejection and the relationship between the mucosal changes and chronic rejection.

IS2-04 The Challenge of Acute Rejection in Small Bowel Transplantation

IS2-04 The Challenge of Acute Rejection in Small Bowel Transplantation

Characterization of the Ileal Microbiota in Rejecting and Nonrejecting Recipients of Small Bowel Transplants

Small bowel transplantation can be a life-preserving procedure for patients with irreversible intestinal failure. Allograft rejection remains a major source of morbidity and mortality and its accurate diagnosis and treatment are critical. In this study, we used pyrosequencing of 16S ribosomal RNA gene tags to compare the composition of the ileal microbiota present during nonrejection, prerejection and active rejection states in small bowel transplant patients. During episodes of rejection, the proportions of phylum Firmicutes (p < 0.001) and the order Lactobacillales (p < 0.01) were significantly decreased, while those of the phylum Proteobacteria, especially the family Enterobacteriaceae, were significantly increased (p < 0.005). Receiver-operating characteristic analysis revealed that relative proportions of several bacterial taxa in ileal effluents and especially Firmicutes, could be used to discriminate between nonrejection and active rejection. In conclusion, the findings obtained during this study suggest that small bowel transplant rejection is associated with changes in the microbial populations in ileal effluents and support microbiota profiling as a potential diagnostic biomarker of rejection. Future studies should investigate if the dysbiosis that we observed is a cause or a consequence of the rejection process.

Potential of intestinal microbiota profile as a diagnostic biomarker of small bowel transplant rejection

Transplantation: Potential of intestinal microbiota profile as a diagnostic biomarker of small bowel transplant rejection

PP73 FROM CHILDHOOD TO ADOLESCENCE: THE COELIAC DISEASE EXPERIENCE FROM THE POINT OF VIEW OF THOSE WHO ARE GROWING UP AND THOSE WHO ARE TAKING CARE OF THEM

Stool calprotectin is useful in monitoring rejection in small bowel transplantation. We report about our initial experience in Children’s Hospital “Bambino Gesu” in Rome on monitoring gut rejection by using stool calprotectin together with intestinal biopsies. Case 1: a 12 year-old boy underwent at the age of 8 SBTx for short gut syndrome; he experienced one ACR, recovered on steroid bolus and he did well for 6 months. Sirolimus was started for initial renal damage, but it had to be discontinued for severe thrombotic micro-angiopathy. A second severe ACR occurred 1 year after transplant and again medical therapy was effective in recovery. After 3 years of well being, with no previous evidence of rejection at histology, he was admitted in Rome for acute diarrhea following Rotavirus infection. Hystology revealed ACR, initially treated by steroid without any effects so repeated steroid bolus, infliximab and mesenchymal cell infusion were administered, but severe exfoliative rejection led to re-transplant, performed in Rome on TAC, steroid, MMF and basiliximab; at + 3 months, CMV enteritis occurred, successfully treated by ganciclovir. Before and after re-Tx, stool calprotectin levels were strict monitoring: normal levels ( 1000 mcg/g) if severe ACR, while in CMV infection levels were always below 800 mcg/g. Case 2: C.S. is now a 10 yr-old boy affected by CIPO who underwent SBTx at the age of 7 for recurrence of severe dehydration and hemorrhagic events; surgical procedure was uneventful, on basiliximab, TAC and steroid therapy. Six months after transplant he experienced ACR and severe CMV enteritis, with complete recovery. The follow-up was continued in Rome, where he underwent protocol biopsies without any evidence of rejection so far. Stool calprotectin levels were always within normal ranges (<250 mcg/g), according to histology. In our experience stool calprotectin levels appear to correlate to gut inflammation, and high levels seem to be more associated to rejection. This could be a useful tool to suspect graft dysfunction.

Association Between Panel Reactive Antibodies and Acute Small Bowel Rejection: Analysis of a Series of 324 Intestinal Transplants

Introduction Panel reactive antibodies (PRA) to class I and II HLA molecules have been associated with acute kidney graft rejection, but their role in small bowel transplantation has not been characterized. Methods Since 1994, 324 SBT, alone or as multivisceral transplantation (MVT), have been performed in 286 patients. Routine and surveillance biopsies were performed to rule out or confirm acute rejection (AR), and PRA quantification was performed at varying intervals. We obtained data from 110 patients and 651 PRA measurements. While AR grade (mild to severe, grades 1–3) was determined by histopathological analysis, the status of no AR was determined also by clinical data. When biopsy samples or PRA measurements were frequent around an AR episode within periods of 7 days, the highest value was used. Results A comparison could be made between 259 instances in which there was a PRA measurement and simultaneous rejection evaluation. Positive PRA showed association with AR ( P < 0.001). The positive and negative predictive values were 44% and 79%, respectively. No correlation was found in the severity of rejection. Conclusion The presence of increased levels of PRA is a risk factor of rejection in small bowel transplantation. Alloantibody-mediated injury to the graft contributes frequently to acute rejection of small bowel, and it is associated with cell-mediated immunity in variable proportion.

International Grading Scheme for Acute Cellular Rejection in Small-Bowel Transplantation: Single-Center Experience

A standardized grading scheme for the assessment of acute cellular rejection (ACR) in small-intestine transplantation was proposed in 2003 at the Eighth International Small Intestinal Transplantation Symposium. We have implemented the current grading scheme for ACR in small-bowel transplantation since October 2003. The pathologic diagnoses of those small-intestine biopsy samples, including ACR grade and other supplementary findings were evaluated. A total of 3484 small intestine biopsy samples from 155 patients were available for evaluation in this study. Frequency of grades 0, indeterminate, 1, 2, and 3 acute cellular rejection was 33.9%, 49.1%, 12.6%, 3.7%, and 0.8%, respectively. Duration of ACR episode strongly correlated with grade of ACR episode ( P < .001). Other supplementary findings included acute vascular rejection component, 2.2%; increase in lymphoplasmacytic infiltrate in lamina propria, 15.7%; mucosal fibrosis, 0.4%; and regenerative changes, 0.3%. Our data substantiate that this grading system is reliable and useful for clinical decision making in bowel transplantation. We suggest that an assessment and quantification of supplementary findings be considered a component of the International Pathology Grading Scheme.

Immediate Antibody-Mediated (Hyperacute) Rejection in Small-Bowel Transplantation and Relationship to Cross-Match Status and Donor-Specific C4d-Binding Antibodies: Case Report

Background The role of preformed donor-specific antibodies (DSAs) as a barrier to isolated intestinal transplantation (ITx) remains ambiguous; thus, a positive cross-match has not been a contraindication to ITx. Objective To report the case of a patient with Crohn's disease who underwent ITx and developed immediate antibody-mediated rejection on reperfusion of the allograft. Methods Percent reactive antibody testing was performed using pretransplantation serum samples and at transplantation using bead-based assays (Luminex, Luminex Corp, Austin, Tex) and flow cytometry solid-phase assays (FlowPRA single-antigen beads (One Lambda, Inc, Canoga Park, Calif). Serologic tests, flow cytometry cross-matching, and flow cytometry assays of C4d-binding serum antibodies were also performed. Histologic and immunofluorescent analysis of biopsy specimens was performed. Results HLA typing revealed no sharing of class I or II antigens between donor and recipient. Pretransplantation donor-specific antibodies (DSA) were present at transplantation. Cross-matching (performed during surgery) was positive for class I and II by serologic testing and flow cytometry. After reperfusion, the graft immediately developed severe ischemic injury and arteritis on mucosal biopsy specimens, with immunoglobulin deposition. The DSA C4d binding antibodies were also present. After intense immunosuppression and plasmapheresis, the graft and the biopsy histologic findings showed marked improvement (day 2). By day 7 posttransplantation, patient and graft status were stable. The patient has remained clinically stable for more than a year after transplantation. Conclusions Pretransplant DSA in ITx can be a risk factor for immediate (hyperacute) but potentially reversible antibody-mediated rejection. Thus, pretransplantation DSA and cross-match results are critical components to be considered in patients awaiting or undergoing ITx.

Intestinal Transplantation Comes of Age

Intestinal transplantation has evolved as a creditable therapeutic option that offers the only chance for cure for patients with intestinal failure who fail parenteral nutrition. The Editors of Transplantation are pleased to publish in this issue the first group of a series of selected articles based on papers presented at the Xth International Small Bowel Transplantation Symposium held in Los Angeles, CA on September 6–8, 2007. All of the articles to be published from this meeting have undergone our standard peer review process. The first articles included in this issue are described below. Additional articles will be published in succeeding issues. The intestine is less tolerant of ischemia than most other transplanted solid organs and, due to frequent significant donor organ size restraints in the majority of intestine recipients, donors are less likely to be procured locally, therefore emphasizing the need to minimize ischemia time. Schaefer et al. (Transplantation 2008; 85: 1300–1310) evaluated the efficacy of intravenous glycine administration in minimizing certain phenomena commonly associated with ischemia–reperfusion injury in a rat intestine model. Their data suggest that perioperative glycine treatment reduces molecular and cellular inflammatory responses within the graft and improves smooth muscle dysfunction posttransplantation. Protocol endoscopy with biopsy has been widely adopted as the standard for small bowel transplant rejection monitoring, but it is invasive, costly, and can be associated with complications. Akpinar et al. studied the use of Fecal Calprotectin levels (FCL) as a possible non-invasive marker for monitoring in small bowel transplant patients (Transplantation 2008; 85: 1281–1286). They present data to show that although no significant FCL difference was found between rejection and inflammation, FCL evolution in individuals could predict rejection days before histopathological diagnosis, suggesting its potential usefulness as a prescreening marker to avoid unnecessary biopsies. Induction immunosuppression is now common practice after intestinal and multivisceral transplantation. Vianna et al. (Transplantation 2008; 85: 1290–1293) describe their experience in 27 patients given antithymocyte globulin, rituximab, and steroids as induction therapy with Tacrolimus and tapered steroids as maintenance. One year patient and graft survival was 81% and 76%. Thirteen patients (48%) experienced 19 episodes of acute rejection; patients with multivisceral grafts experienced fewer episodes of acute rejection. Their data suggest that this induction regimen may have a protective effect against posttransplant lymphoproliferative disease and chronic rejection. Mian et al. (Transplantation 2008; 85: 1287–1289) present a retrospective analysis to determine factors affecting survival of intestinal transplantation in very young pediatric patients. Such patients awaiting intestinal transplantation have a high mortality rate due to long waiting times, scarcity of appropriate size donor organs, and mortality due to sepsis and liver failure. In children under 18 months of age, risks factors affecting survival to intestinal transplantation include small body size and advanced liver disease. No differences in residual small bowel length, presence of the colon, number of line infections or number of central lines were identified in the transplant and not transplanted groups. Intestinal transplantation is only one of a continuous of possible treatments for intestinal failure. Andres et al. (Transplantation 2008; 85: 1294–1299) examined the efficacy of repeat surgical bowel lengthening with the so-called reSTEP procedure (Repeat Serial Transverse Enteroplasty) after previous surgical lengthening procedures. They concluded that in the stable patient who is otherwise unable to wean from parenteral nutrition repeat lengthening via a reSTEP surgery resulted in discontinuation of parenteral nutrition in almost half of a carefully selected group of patients. Most importantly, such repeat procedures did not preclude intestinal transplantation. Anthony Monaco Peter J. Morris

Inducible Nitric Oxide Synthase Expression in the Intestinal Muscularis Mediates Severe Smooth Muscle Dysfunction During Acute Rejection in Allogenic Rodent Small Bowel Transplantation

Acute rejection in small bowel transplantation is associated with dysmotility. Therefore, host and organ not only face the threat of destructive immunological processes but also the risk of bacterial translocation, endotoxemia, and systemic inflammatory response syndrome. We hypothesized that dysmotility during acute rejection is based on an alloreactive leukocyte infiltrate and coexpression of the kinetically active mediator inducible nitric oxide synthase (iNOS) in the muscularis propria. Allogenic and isogenic rat small bowel transplantation (SBTx; Brown Norway [BN] to Lewis and BN to BN) was performed without immunosuppression. Animals were sacrificed 4 and 7 d after SBTx. Leukocyte infiltration and iNOS protein was investigated by immunohistochemistry and immunohistology. Real-time reverse transcription polymer chain reaction was used to detect iNOS expression. Griess reaction was used to evaluate NO production. Spontaneous, bethanechol-stimulated, and L-N(6)-(1-iminoethyl)-L-Lysin-blocked jejunal circular muscle contractions were measured in a standard organ bath in vitro. On d 7 after SBTx, allogenic transplanted animals showed significant infiltration with ED-1- and ED-2-positive monocytes and macrophages within the muscularis parallel to the manifestation of acute rejection. Additionally, immunohistochemistry localized iNOS protein in leukocytes within the muscularis. Reverse transcription polymer chain reaction showed a significant increase in iNOS mRNA expression (460-fold) in allogenic transplanted muscularis compared to isogenic transplanted muscularis (2.5-fold). Compared to controls, allogenic grafts showed a 73% decrease in smooth muscle contractility, while isogenic grafts showed only an 8% decrease of contractility on d 7. L-N(6)-(1-iminoethyl)-L-Lysin application in vitro significantly improved muscle contractility and decreased NO production. The data show that inflammation associated iNOS expression in the intestinal graft muscularis is involved in motoric graft dysfunction during acute rejection.

International Grading Scheme for Acute Rejection in Small Bowel Transplantation: Implementation and Experience at the University of Miami

In 2003, an international collection of pathologists and clinicians proposed a unified grading system for acute cellular rejection in endoscopically derived small intestine allograft biopsies. This grading system was implemented at the University of Miami over the past 2 years and the results are presented herein. A total of 1136 small bowel allograft biopsies with sufficient tissue for analysis were obtained from 123 hospitalized, clinic, and referral patients. The overall most common diagnosis assessing all time periods was grade IND (40%), and grade 1 rejection or greater was present in 19% percent of biopsies. A suspected vascular component to the acute rejection as identified by specific mucosal vascular changes was present in 6% of cases. Clinical decision making was very consistent with different grades. Our experience has confirmed that this new grading system is reliable and identifies clinical subsets of patients that can receive different therapy. We recommend that this international grading system be implemented for acute cellular rejection in bowel allografts as a means to standardize pathological assessment of alloimmune-induced graft injury, which will allow comparisons between different centers and clinical trials.

Method for diagnosing rejection in small bowel transplantation.

Diagnosis of rejection in small bowel transplantation by the identification of a host-cell infiltrate is hampered by the physiological trafficking of host lymphocytes to the 'gut-associated lymphoid tissue' of the graft. This study compared physiological host-cell infiltration of small bowel grafts with that occurring in rejection and stable immunosuppression. Physiological host-cell infiltration, where the graft does not present an immune stimulus to the host, was assessed by transplanting bowel from DA to (DA x PVG) F1 hybrid rats. The extent of host-cell infiltration was determined by immunohistochemical analysis. In the lamina propria, considerable infiltration by host cells was seen, although it was significantly less than that in rejection or stable immunosuppression. By contrast, host cells were seen in the intraepithelial compartment only in rejection. Host-cell infiltration in the absence of an allogeneic stimulus suggests that histological identification of host cells in the lamina propria is not necessarily indicative of rejection. However, the presence of host cells in the intraepithelial compartment is specific for rejection in small bowel transplantation.

A study of the relationship between the graft length, site, and rejection in small bowel transplantation

A study of the relationship between the graft length, site, and rejection in small bowel transplantation

Rejection following donor or recipient preoperative treatment with FTY720 in rat small bowel transplantation

Background Severe rejection of small bowel transplantation (SBTx) has been ascribed to abundant lymphoid tissues in the small intestine without well-established evidence. However, the role of donor lymphocytes in rejection is still unclear. The novel immunosuppressant, FTY720, is reported to transfer peripheral blood lymphocytes (PBLs) to lymphoid tissues such as mesenteric lymph nodes (MLNs) and Peyer patches (PP). In the present study, the number of donor lymphocytes in the graft was increased by FTY720, and the influence on rejection was studied in a rat model. Furthermore, the number of the PBL of recipient was decreased by FTY720 before SBTx and the effect on rejection was examined. Materials and methods Orthotopic total SBTx was performed in Brown–Norway and Lewis rats. In the donor pretreatment study, FTY720 was administrated to donor rats 24 h prior to harvesting to increase the number of graft lymphocytes (FTY donor-pretreated group). In contrast, MLNs were surgically removed from the grafts to decrease the number of graft lymphocytes (MLN-resected group). In the recipient pretreatment study, FTY720 was administrated to recipient rats 24 h before SBTx to decrease recipient PBL (FTY group). In contrast, a subclinical dose of cyclosporine A (CsA) was administrated after SBTx (CsA group). Rats were administrated preoperative FTY720 combined with post-SBTx CsA (FTY+CsA group). Graft survival, pathology, lymphocyte count, and subtype were examined. Results In the donor pretreatment study, pretreatment with FTY720 did not enhance graft rejection. MLN resection did not prolong graft survival. In the recipient pretreatment study, FTY720 caused a significant reduction in the number of infiltrating lymphocytes in the graft, as well as the percentage of recipient CD4 + and CD25 + cells within the graft. FTY720 and CsA synergistically prolonged graft survival. Conclusion SBTx rejection correlated with the number of recipient PBL, and not with the number of donor lymphocytes transplanted together with the graft. The pretreatment of the recipient with FTY720 was effective in the case of combined use of the low-dose postoperative CsA.

Laser-Doppler flowmetry is reliable for early diagnosis of small-bowel acute rejection in the mouse.

The purpose of the study was to investigate intestinal mucosal perfusion in mouse small-bowel transplantation (SBT), using laser-Doppler flowmetry. Heterotopic SBT was performed in syngeneic and allogeneic combinations. Mucosal perfusion was measured both in the native and in the grafted intestine at time of surgery and at 1, 3, 6, and 8 days postoperatively. Histology specimens were obtained at the same time and graded for rejection. No rejection was seen in the syngeneic group at any of the time points studied. The allografts displayed significant decreased mucosal perfusion on postoperative days 3, 6, and 8. Rejection was histologically evident on postoperative days 6 and 8. Laser-Doppler perfusion in the rejecting intestinal allograft was decreased before onset of histological features of rejection. Mucosal blood flow measured by laser-Doppler could be used as an early indicator of acute rejection in SBT.

Evaluation of the Acetaminophen Absorption Test for Early Detection of Orthotopic Small Bowel Transplant Rejection

We evaluated the efficiency of the acetaminophen (AC) absorption test as a marker of graft rejection in orthotopic small bowel transplantation (SBTX) in rats. Brown Norway (BN) rats were used as donors and Lewis (LEW) rats as recipients. Orthotopic allogenic SBTX was accomplished using a cuff technique for vessel anastomosis. Animals were divided into: group A (n = 9), untreated; group B (n = 15), extended small bowel resection; group C (n = 12), syngeneic SBTX without immunosuppressants; group D (n = 15), allogenic SBTX with tacrolimus (0.1 mg/kg per day); group E (n = 15), allogenic SBTX with tacrolimus (0.5mg/kg per day). Serum AC was measured 15 min following the instillation of 0.15 g/kg AC into the stomach on postoperative days (POD) 1, 3, and 7. Grafts were examined histologically. The group D grafts showed progressive acute rejection histologically, from normal on POD 1, to moderate on POD 3, and severe on POD 7. Serum AC in group D decreased significantly from 53.1 +/- 3.9 microg/ml on POD 1, to 35.0 +/- 12.0 microg/ml on POD 3, and 10.9 +/- 5.6 microg/ml on POD 7. No remarkable change was observed in the other groups. Serum AC correlated well with histological changes in rats subjected to SBTX, resulting in acute rejection. The AC absorption test could be useful for detection of progressive graft rejection in clinical SBTX.

Allograft rejection of small bowel transplantation in pigs.

Small bowel allograft rejection in large animals has yet to be well defined. There are no specific early signs of graft rejection. The present experiments were undertaken to compare acute small bowel allograft rejection in pigs with and without FK506 and also to examine the usefulness of mucosal biopsies. Thirty-six outbred Large-White pigs were divided into (1) group 1 (n = 9): nonimmunosuppressed recipients; (2) group 2 (n = 8): FK506-immunosuppressed recipients; (3) group 3 (n = 2): autotransplant controls; and (4) donors (n = 17). Orthotopic small bowel transplantations were performed with Thiry-Vella loops for daily biopsies. The survival rate of group 2 was significantly longer than that of group 1 (P < 0.05). One best survivor in group 2 was killed at postoperative day (POD) 365. Treatment by FK506 prevented rejection, but most of the pigs died of pneumonia. In group 1, rejection began on POD 3 and progressed to severe rejection rapidly within 7 days. In group 2, rejection began from POD 6 to POD 8, but either remained mild or spontaneously improved. The differences in the routine laboratory data and the tumor necrosis factor-alpha level were not evident between the groups. Histological studies of repeated graft biopsies are thus considered to be essential for detecting signs of graft rejection.

Endoscopic findings in transplanted allo-intestine of rats after discontinuance of immunosuppressive agent.

In clinical practice, graft rejection in small-bowel transplantation should be diagnosed before irreversible condition of the graft. We have already reported the usefulness of endoscopic examination for the early detection of acute rejection in a rat model. Here we evaluated rejection after discontinuance of methyl-deoxyspergualin by endoscopy. Heterotopic small-bowel transplantation was performed by the cuff method from a DA to a LEW rat. Endoscopic and histological examinations were performed through the stomas. Two-week administration of methyl-deoxyspergualin significantly prolonged graft survival. Graft rejection after discontinuance of the agent occurred much more slowly than rejection without the immunosuppressive drug. Erosive mucosal changes were endoscopically observed in the early phase of rejection in rats that did not receive the immunosuppressant. However, endoscopic findings after discontinuance of methyl-deoxyspergualin indicated edematous changes and thickening of the wall without erosion, and, histologically, the grafted intestine showed slowly-progressing rejection with flattened villi. If we pay attention to edematous changes and hardening of intestinal wall, and take selective biopsies, endoscopic examination may improve the early diagnosis of slowly progressive rejection in the clinical setting.

The Plasma FK506-Binding Protein 12 Level is Related to Acute Cellular Rejection in Small Bowel Transplantation

Since FK506 binding protein (FKBP12) inhibits dose-dependently the immunosuppressive activity of FK506 in vitro, plasma FKBP12 levels were measured after rat small bowel transplantation (SBTx). The mean plasma FKBP12 level in untreated recipients increased significantly at the onset of acute cellular rejection (ACR) compared to that in FK506-treated recipients without rejection at the same time after SBTx (P < 0.05). In both groups, however, the mean plasma FKBP12 level did not increase at 1 day after SBTx. These results suggest that plasma FKBP levels may be affected by ACR, but not by ischemia-reperfusion injury. Therefore, the plasma FKBP12 level should be considered as one of the parameters related to the immunosuppressive activity of FK506 in SBTx.

Serotonin (5-HT): An enteroendocrine marker of rejection after small bowel allotransplantation in the pig

The histopathologic findings of mucosal epithelial cell injury in acute and chronic rejection in small bowel transplantation are well known. Several studies have been done on the pig either as autotransplantation, allotrans-plantation, orthotopic, or enterotopic transplantation, with or without immunosuppression. Very few investigations on the enteroendocrine system have been done. In particular, none have been done on rejection in pigs after intestinal transplantation. On the other hand, changes in the enteroendocrine markers (somatostatin and chromogranin A) have been examined in detail after auxiliary small bowel transplantation in dogs without immunosuppression, showing no apparent changes on the 7th postoperative day, even if in a severe rejection status. Recent studies on rats have evaluated the presence of serotonin after small bowel allotransplantation with different times of preservation, and after reperfusion. The authors concluded that the number of serotonin-positive cells decreased with a preservation time of more than 1 hour in Ringer lactate at 4°C. We too have examined the modifications of argentaffin as well as serotonin-positive cells in the harvested small bowel of pigs perfused with Belzer solution (4°C) and preserved in Ringer lactate at 4°C, after preservation and reperfusion in the combined liver-small bowel allotransplantation. We noticed that the argentaffin and serotonin cells were preserved up to 20 hours and that after reperfusion the most important injury was due to the disappearance of these cells from the crypts. In this study, we studied the modifications of the intestinal enterochromaffin cells after combined liver-small bowel and small bowel alone allotransplantation in pigs, with the aim of evaluating a correlation with rejection.