Small bowel transplantation has become the treatment of choice for patients with chronic gut failure whose illness cannot be maintained on home parenteral nutrition. Outcomes have improved as a result of refinements in patient selection, surgical techniques, and the prevention, diagnosis, and treatment of graft rejection. Early listing is important because of the shortage of organ donors. Rejection rates are still 50% or more, despite the use of potent immune suppression. Sepsis rates are also higher for patients who have had small bowel transplantation than for those who have received other organs because of bacterial translocation from the gut secondary to preservation injury and graft rejection. Graft and patient survival rates after small bowel transplantation are comparable to rates after lung transplantation. Successful transplant recipients resume unrestricted oral diets.

Small bowel transplantation

The term ‘intestinal failure’ is now often used to describe gastrointestinal function insufficient to satisfy body nutrient and fluid requirements. The first recognized condition of intestinal failure was short bowel syndrome. Severe motility disorders such as chronic intestinal pseudo-obstruction s

Intestinal transplantation: indications, results and strategy.

Background

This study describes the impact of prolonged cold storage on microvascular reperfusion injury of transplanted rat small bowel isografts.



Methods

In vivo fluorescence microscopy was used to assess intestinal microcirculation after 6, 12, 18 and 24 h of cold (4°C) ischaemia in University of Wisconsin solution and 20–90 min of reperfusion. Sham-operated animals served as controls.



Results

Whereas 6 and 12 h of ischaemia did not affect functional capillary density of the intestinal graft mucosa, villous perfusion was significantly impaired after 18 and 24 h of cold preservation. Similarly, microvascular perfusion of circular and longitudinal muscle was not affected after 6 h, but deteriorated following prolonged cold ischaemia. Leucocyte–endothelial cell interaction in submucosal venules was significantly enhanced after 6 h of ischaemia with peak values after 12 and 18 h. A progressive reduction of lymphatic capillary drainage indicated an ischaemia time-related deterioration in graft function.



Conclusion

The results provide evidence that leucocyte–endothelial cell interaction in submucosal venules of the transplanted intestine is a primary step in the manifestation of reperfusion injury following short periods of cold ischaemia. © 1998 British Journal of Surgery Society Ltd

In vivo assessment of the influence of cold preservation time on microvascular reperfusion injury after experimental small bowel transplantation.

All studies involving small intestinaltransplantation and absorptive function are reviewed.The effects ischemia-reperfusion, lymphatic disruption,denervation, rejection, immunosuppressive medication, and infection are elucidated as far as thestudies allow. Species differences are discussed.Conclusions regarding the major absorptive defects aredrawn.

Absorptive function following small intestinal transplantation.

Clinically, FK506 is superior to CsA after solitary small bowel transplantation (SBTx). Development of diarrhea after SBTx has been the rationale for adding the colon to small bowel grafts. However, the additional lymphoid and bacterial content transferred with total small plus large bowel transplants (TBTx) might aggravate the alloimmune response-rejection and graft-versus-host disease (GVHD)-and increase the risk of infection. We studied the incidence of rejection, GVHD, and infection after TBTx and the impact of CsA versus FK506. We performed orthotopic TBTx with portal drainage after total enterectomy in outbred Yorkshire Landrace pigs, divided into 3 groups : control pigs (n=6) received no immunosuppression ; CsA pigs (n=14) received CsA (5 mg/kg), antilymphocyte globulin (10 mg/kg for 10 days), prednisone (2 mg/kg), and AZA (2.5 mg/kg) ; and FK506 pigs (n=9) received FK506 (0.2 mg/kg) and prednisone (2 mg/kg). Trough CsA whole blood levels were >400 ng/ml for the first 7 days and >200 ng/ml thereafter. FK506 levels were >15 ng/ml. We excluded from further analysis 5 early deaths (<3 days) due to anesthesiologic (n=2) or technical reasons (n=3). Median survival of control pigs was 9.5 days (range, 4-13). Cyclosporine did not extend survival: median, 9 days (range, 5-31) (P=0.6). FK506 prolonged survival : median, 37 days (range, 21-49) (P<0.001 vs. control and CsA pigs). Of FK506 pigs, 60% gained weight (+75 g/day), whereas 100% of controls and 75% of CsA pigs lost weight (-550 g/day and -300 g/day, respectively). All control pigs died of rejection within 2 weeks versus none of the FK506 pigs. However, 36% of CsA pigs died of rejection. Groupwise comparison showed less rejection in FK506 versus control pigs (P<0.001) and in FK506 versus CsA pigs (P<0.03), but no difference between CsA and control pigs. None of the control pigs died of GVHD versus 18% of CsA pigs (by day 31) and 37% of FK506 pigs (by day 49). Groupwise comparison showed increased GVHD in FK506 versus control pigs (P<0.001) and a tendency toward increased GVHD in FK506 versus CsA pigs (P=0.08). None of the control pigs died of infection alone versus 22% of CsA pigs (by day 31) and 67% of FK506 pigs (by day 49). Groupwise comparison showed increased infection in FK506 versus control pigs (P<0.001). We detected significant endotoxemia early and late postoperatively. But we saw no specific correlation between endotoxemia, rejection, GVHD, or infection. Based on this study, we have drawn several conclusions: (1) In untreated pigs, TBTx provokes a severe rejection response, but no lethal GVHD. (2) Cyclosporine and particularly FK506 pigs have a high incidence of infection and lethal GVHD, a complication that we had not seen after solitary SBTx. (3) FK506 is superior to CsA in controlling rejection and in prolonging graft and recipient survival ; FK506, however, does not reduce GVHD, but rather tends to augment it. (4) TBTx causes endotoxemia. As with solitary SBTx, FK506 is superior to CsA after TBTx. However, long-term survival is difficult to achieve in FK506 recipients because of the development of GVHD and infection.

Combined transplantation of small and large bowel: FK506 versus cyclosporine A in a porcine model

This study tests the hypothesis that small bowel transplantation alters the function of the intestine. The function of the small intestine was investigated after syngeneic (BN----BN or Lew----Lew) and fully allogeneic (BN----Lew) orthotopic total small intestinal transplantation (SIT) using a two-stage model. All animals were treated with cyclosporine A throughout the 60-day study period. Syngeneic transplantation reduced weight gain in the (BN----BN) rats, but not in the (Lew----Lew) animals. Allogeneic transplantation caused a reduction in weight gain for the first 30 days posttransplantation, which may have been associated with graft-versus-host disease. Thereafter, the rate of growth of allogeneic SIT animals was normal. Dietary fat absorption was reduced in all groups of transplanted animals. Intestinal permeability to mannitol and polyethylene glycol 400 (PEG-400) was increased by syngeneic transplantation in all groups, with further permeability increases to mannitol, lactulose, PEG-400, and 51Cr-EDTA after allogeneic SIT. The glucose-stimulated intestinal short circuit current was reduced by both syngeneic and allogeneic SIT, but the maximal active transport rate for glucose uptake was increased, as was the passive uptake of fatty acids. These functional alterations were not associated with changes in intestinal morphology or evidence of rejection. These findings demonstrate that: (1) SIT results in significant changes in the transport characteristics of the bowel, but these have a minimal impact on the well-being of the animal overall; (2) SIT induces an increase in intestinal permeability to mannitol and PEG-400, with a further increase in permeability to all markers following allogeneic SIT; (3) following SIT, and the immune events associated with allogeneic SIT, significant adaptation of the transplanted intestine occurs. We suggest that denervation of the small intestine after SIT is the underlying cause of the changes observed.

Intestinal function following allogeneic small intestinal transplantation in the rat.

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Intestinal function following allogeneic small intestinal transplantation in the rat.