Dissociation between peripheral blood chimerism and tolerance to hindlimb composite tissue transplants: preferential localization of chimerism in donor bone.

BACKGROUND: Mixed chimerism induces donor-specific tolerance to composite tissue allotransplants (CTAs). In the present studies, we used a nonmyeloablative conditioning approach to establish chimerism and promote CTA acceptance. METHODS: Wistar Furth (RT1A(u)) rats were conditioned with 600 to 300 cGy total body irradiation (TBI, day-1), and 100 x 10(6) T-cell-depleted ACI (RT1A(abl)) bone marrow cells were transplanted on day 0, followed by a 11-day course of tacrolimus and one dose of antilymphocyte serum (day 10). Heterotopic osteomyocutaneous flap transplantation was performed 4 to 6 weeks after bone marrow transplantation. RESULTS: Mixed chimerism was initially achieved in almost all recipients, but long-term acceptance of CTA was only achieved in rats treated with 600 cGy TBI. When anti-alphabeta-T-cell receptor (TCR) monoclonal antibody (mAb) (day-3) was added into the regimens, donor chimerism was similar to recipients preconditioned without anti-alphabeta-TCR mAb. However, the long-term CTA survival was significantly improved in chimeras receiving more than or equal to 300 cGy TBI plus anti-alphabeta-TCR mAb. Higher levels of donor chimerism were associated with CTA acceptance. The majority of flap acceptors lost peripheral blood chimerism within 6 months. However, donor chimerism persisted in the transplanted bone at significantly higher levels compared with other hematopoietic compartments. The compartment donor chimerism may be responsible for the maintenance of tolerance to CTA. Long-term acceptors were tolerant to a donor skin graft challenge even in the absence of peripheral blood chimerism. CONCLUSIONS: Mixed chimerism established by nonmyeloablative conditioning induces long-term acceptance of CTA, which is associated with persistent chimerism preferentially in the transplanted donor bone.

A modified model of hindlimb osteomyocutaneous flap for the study of tolerance to composite tissue allografts.

Composite tissue allotransplantation (CTA) is the new frontier in transplantation. More than 25 hand allograft transplants have been performed worldwide, and the feasibility has been well established. The classical experimental model of CTA involves rat orthotopic hindlimb transplantation, a time-consuming procedure associated with high mortality and morbidity. We describe a rat heterotopic osteomyocutaneous flap that serves as a nonfunctional CTA, allowing the study of tolerance induction to a highly antigenic vascularized allograft of bone, muscle, and skin while minimizing the morbidity and mortality of full hind limb transplantation. In the present studies, we explored whether establishing chimerism by nonmyeloablative conditioning would induce tolerance to CTA. When compared with the classic hind limb transplantation model, these results demonstrate that our heterotopic hind limb flap is less morbid and as an effective experimental model for the study of CTA tolerance.

Bilateral reduction mammoplasty in combination with lumpectomy for treatment of breast cancer in patients with macromastia.

BACKGROUND: Bilateral reduction mammoplasty has been described as a surgical option for treatment of breast cancer in women with large, pendulous breasts. Using this technique can provide unique surgical oncologic challenges. METHODS: Retrospective chart review. RESULTS: Thirty-seven patients were identified. The average weight of tissue removed was 653 g. Tumor size ranged from 0.6 to 5.2 cm. One patient had microscopically positive surgical margins on final pathology. The tumor bed was not marked, and completion mastectomy was required. Two patients had unexpected malignancy in the contralateral breast. One patient required completion mastectomy for positive nonoriented margins. In another patient, tissue from the contralateral side was oriented, and mastectomy was avoided. CONCLUSIONS: Bilateral reduction mammoplasty with lumpectomy is an ideal option in women with macromastia. We recommend marking the tumor bed on the flaps and pedicle as well as orienting tissue removed from the contralateral side as maneuvers that will decrease need for completion mastectomy.