Donor-Specific Portal Blood Transfusion in Intestinal Transplantation

Gruessner, Rainer W.G.; Nakhleh, Raouf E.; Harmon, James V.; Dunning, Michele; Gruessner, Angelika C.

doi:10.1097/00007890-199807270-00004

Cited by 28 publications

(6 citation statements)

References 17 publications

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“…Several previous studies have shown prolonged intestinal allograft survivals to 100–200 days in dogs and pigs under CYS, prednisone, or FK506 regimens (12–18). In those studies, the majority of recipients sustained rejection, malnutrition, and infectious complications.…”

Section: Discussionmentioning

confidence: 99%

Long‐Term Function and Morphology of Intestinal Autografts and Allografts in Outbred Dogs

Iwanami¹,

Ishikawa²,

Nalesnik³

et al. 2003

American Journal of Transplantation

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Although small bowel transplantation (SBTx) has become a clinical option, there have been few studies of long-term function and histopathology of intestinal grafts. Unrelated mongrel dogs received autologous (n = 4) or allogeneic (n = 11) orthotopic SBTx under oral cyclosporine. Intestinal graft function and routine/ immunohistopathology of full-thickness intestine were studied. Six allograft and all isograft recipients had comparable body weight gain and are currently alive (> 420 days). Five allograft recipients were sacrificed because of significant body weight loss and malnutrition at a median of 119 days. Analyses of intestinal function in long-surviving recipients revealed marginal reduction of D-xylose/cyclosporine absorption, intestinal transit time, in vitro muscle contractility, and mucosal enzyme activity compared with normal dogs. However, these changes were insignificant and no statistical difference was seen between auto and long-surviving allografts. In histopathological analysis, long-surviving allografts had normal mucosa with submucosal, muscularis propria, and perineural (Auerbach's plexus) inflammation. Five allorecipients with malnutrition had mucosal atrophy/erosion and significantly reduced intestinal absorption and motility. Thus, denervated intestinal allografts are able to efficiently digest and absorb nutrients to support life. Results also indicate that these allografts experienced low-grade chronic rejection as evidenced in the submucosa and muscle layers, despite the lack of clinical symptoms.

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Section: Discussionmentioning

confidence: 99%

Long‐Term Function and Morphology of Intestinal Autografts and Allografts in Outbred Dogs

Iwanami¹,

Ishikawa²,

Nalesnik³

et al. 2003

American Journal of Transplantation

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“…Consistent with our current findings, in a later study from the same center that analyzed recipients on tacrolimus, no immunologic impact of portal venous drainage was observed (43). Similarly, in an experimental porcine intestinal transplant study on the effect of tacrolimus vs. cyclosporine A immunosuppression, and of portal vs. systemic antigen infusion in portally drained small intestinal grafts, the type of immunosuppressive agent was more significant than the route of perioperative antigen administration (15). Thus, our results analyzed in conjunction with historical and experimental observations suggest that, while portal venous drainage may confer a modest immunologic benefit, any such benefit is relatively insignificant when compared with the combined effect of more powerful immunosuppression and increasing center experience: according to our multivariate analysis, even for recipients on tacrolimus, outcomes were better in the current than in the previous era.…”

Section: Discussionmentioning

confidence: 99%

“…Previous experimental studies have demonstrated that antigen presented to the liver via the portal vein can result in the induction of antigen‐specific systemic hyporesponsiveness (1–14). The distinct mechanisms leading to such a functionally tolerant state are not completely understood, but require the processing of antigen by hepatic macrophages (15–18).…”

Section: Introductionmentioning

confidence: 99%

Impact of Portal Venous Pancreas Graft Drainage on Kidney Graft Outcome in Simultaneous Pancreas-Kidney Recipients Reported to UNOS

Troppmann

Gjertson

Cecka

et al. 2004

American Journal of Transplantation

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Clinical data on the potential immunologic impact of portal (PD) vs. systemic (SD) venous pancreas graft drainage on outcome remains controversial.We reviewed the UNOS database to study the effect of PD vs. SD on the incidence of kidney graft rejection and survival in first cadaveric simultaneous pancreas-kidney (SPK) recipients transplanted 1994-2001. We studied three groups: all SPK (n = = 6629, 13% PD) (group I), SPK on tacrolimus (n = = 3563, 17% PD) (group II), and SPK on tacrolimus performed at centers with significant PD experience (n = = 948, 46% PD) (group III). The cumulative kidney graft rejection incidence for PD vs. SD was only significantly different in group I (for PD vs. SD, respectively: at 6 months, 31% vs. 36% [p = = 0.015]; at 1 year, 37% vs. 43% [p = = 0.006]). Kidney graft survival was similar in all groups for PD vs. SD. Multivariate analysis of group III showed only transplantation during the earlier era (1994-96), but not SD, to be an independent risk factor for kidney graft rejection.Portal venous pancreas graft drainage does not affect kidney graft rejection and survival in SPK recipients on tacrolimus. Our data suggests that the efficacy of current immunosuppressive protocols and increasing center experience are clinically much more relevant than any potential immunologic advantage of portal venous drainage in SPK recipients.

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“…But this therapy led to a higher risk of death from the development of severe infections, which stemmed from the side effects of immunosuppression. 56 Murase et al eliminated mature lymphoid elements from the bowel allografts using ex vivo irradiation; as a result, chronic rejection was prevented with adjunct donor BMC infusion without causing GVHD. 57 For decreasing the morbidity and mortality associated with the use of lethal conditioning regimens in a rat small bowel transplant model, low doses of TBI with ATS serum were also used.…”

Section: Intestine Transplantationmentioning

confidence: 99%

Chimerism and bone marrow based therapies in transplantation

Siemionow

Nasır

2007

Microsurgery

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Composite tissue allotransplantation holds a great potential for providing increased knowledge of anatomy and microsurgical experience for life-enhancing reconstructions. Many transplant cases around the world have made this a clinical reality at the present time. Composite tissue allotransplants contain multiple tissue types, including bone, muscle, vessels, nerves, skin, and immune cells and bear a huge antigenic load. Although immunosuppressive drugs are applied successfully to prevent allograft rejection, their side effects pose a barrier to worldwide use. Bone marrow therapy in many tolerance induction protocols, therefore, provides a guide to reaching the target of permanent immunotolerance. Multiple studies suggest that bone marrow is immunomodulatory and may facilitate allograft acceptance. In this review, bone marrow based therapy protocols of clinical and experimental models are presented in two major categories: solid organ and composite tissue transplantation.

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Donor-Specific Portal Blood Transfusion in Intestinal Transplantation

Abstract: Portal DST at the time of total bowel transplantation and posttransplant immunosuppression with tacrolimus prevent rejection and significantly increase graft survival. The combination of portal antigen presentation and tacrolimus needs to be studied in clinical bowel transplantation.

Cited by 28 publications

References 17 publications

Long‐Term Function and Morphology of Intestinal Autografts and Allografts in Outbred Dogs

Long‐Term Function and Morphology of Intestinal Autografts and Allografts in Outbred Dogs

Impact of Portal Venous Pancreas Graft Drainage on Kidney Graft Outcome in Simultaneous Pancreas-Kidney Recipients Reported to UNOS

Chimerism and bone marrow based therapies in transplantation

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