The use of selective lymphadenectomy in malignant blue naevus of the scalp.

Malignant blue naevus (MBN) is a rare cutaneous tumour with a close biological resemblance to malignant melanoma. MBN spreads to regional lymph nodes, creating a dilemma in managing patients with clinically negative nodal basins. Sentinel lymph node (SLN) biopsy has evolved as a powerful staging tool by identifying occult metastatic nodal disease in patients with cutaneous malignancies. Here, we report a patient with MBN of the occipital scalp who underwent wide local excision together with preoperative lymphoscintigraphy and intraoperative radiolymphoscintigraphy and vital dye injection to identify all draining SLNs. No occult nodal disease was identified. This report adds to the growing body of literature supporting the role of SLN biopsy in staging individuals with cutaneous malignancies, including MBN.

Osteomyocutaneous flap as a preclinical composite tissue allograft: swine model.

Composite tissue allotransplantation (CTA) constitutes one of the last frontiers of microsurgery. Prior to its clinical application, the long-term efficacy of modern immunotherapy must be tested in a pre-clinical CTA model. Based on the concept of osteomyocutaneous forearm flap, we developed a CTA flap model in swine. After identifying the vascular territory of the flaps in six pigs (vascular casting), flaps were transplanted from mismatched donor to recipient pigs (n = 6). Rejection was assessed daily by visual inspection and histopathology of biopsy specimens. Recipient pigs were able to ambulate immediately following surgery. There were no flap failures owing to technical or surgical complications. Rejection occurred over a period of 7 days as manifested by edema, cellular infiltration, epidermalysis, and thrombosis. This pre-clinical flap model is excellent for evaluating the effectiveness of modern immunotherapy because it is anatomically and immunologically relevant and because the minimal morbidity caused to the animal permits long-term studies.

Pharmacokinetic advantage of intra-arterial cyclosporin A delivery to vascularly isolated rabbit forelimb. I. Model development.

Effective antirejection therapy with minimal systemic morbidity is required if limb transplantation is to become a clinical reality. We investigated whether i.a. infusion of cyclosporin A (CSA) into the vascularly isolated rabbit forelimb will distribute drug homogeneously to the tissues and produce higher local drug levels than same-dose i.v. treatment, thereby improving the therapeutic index. CSA 4.0 mg/kg/day was infused continuously via osmotic minipump into either the right brachial artery (i.a. group) or jugular vein (i.v. group) of New Zealand rabbits. Ligation of all muscles at the right mid-arm level was performed in the i.a. group to eliminate collateral circulation and simulate allografting, while leaving bone and neurovasculature intact. On day 6, CSA concentrations were measured in skin, muscle, bone, and bone marrow samples taken from different compartments of the right and left forearms in the i.a. group and right forearm only in the i.v. group. There were no significant differences between compartmental CSA levels in all tissues examined on the locally treated, right side during i.a. infusion, indicating that drug streaming from the catheter tip is not occurring in our model. During i.a. infusion, mean CSA concentrations were 4- to 7-fold higher in the right limb than in the left limb in all four tissues examined. Tissue CSA levels in the left limb were equivalent to those achieved during i.v. infusion, but CSA concentrations in blood, kidney, and liver were higher during i.a. infusion. These favorable, preliminary, single-dose pharmacokinetic results warrant further investigation in our novel rabbit model.

Pharmacokinetic advantage of intra-arterial cyclosporin A delivery to vascularly isolated rabbit forelimb. II. Dose dependence.

A vascularly isolated rabbit forelimb model simulating conditions of composite tissue allografting was used to determine the regional pharmacokinetic advantage achievable in extremity tissue components during i.a. cyclosporin A (CSA) administration. CSA was infused continuously via osmotic minipump into the right brachial artery of New Zealand rabbits at multiple doses ranging from 1.0 to 8.0 mg/kg/day. On day 6, CSA concentrations were measured in aortic whole blood, as well as in skin, muscle, bone, and bone marrow samples from both right and left forelimbs. The variation of right-sided mean CSA concentrations with dose was tissue dependent and saturable in the case of skin and bone, whereas left-sided tissue concentrations correlated significantly with systemic blood levels. At 1.0 mg/kg/day, there were no significant differences between right and left mean CSA concentrations for all four tissues examined. However, with a doubling of the i.a. dose, huge increases in local tissue CSA concentrations were produced with only very modest increases in systemic whole-blood and tissue drug levels, resulting in a 4-fold regional advantage (right/left ratio of CSA concentrations) in bone and bone marrow, 7-fold in muscle, and 14-fold in skin. With further dose increases to 8.0 mg/kg/day, the regional advantage decreased to 4-fold in skin, increased to 9-fold in bone marrow, remained relatively constant in bone, and initially decreased and then increased to 9-fold in muscle. These favorable pharmacokinetic results suggest that reduced, local doses of CSA might be useful in preventing extremity composite tissue allograft rejection with decreased systemic drug exposure.

Pharmacokinetics of intra-arterial delivery of tacrolimus to vascularly isolated rabbit forelimb.

A vascularly isolated rabbit forelimb model simulating conditions of composite tissue allografting was used to determine the regional pharmacokinetic advantage achievable in extremity tissue components during i.a. tacrolimus (FK506) administration. FK506 was infused continuously via osmotic minipump into the right brachial artery of New Zealand rabbits at 0.05, 0.1, and 0.2 mg/kg/day. On day 6, FK506 concentrations were measured in aortic whole blood, heart, lung, liver, kidney, spleen, and fat, as well as in skin, muscle, bone, and bone marrow samples from both right and left forelimbs. The relative tissue concentrations of FK506 in descending order were [spleen approximately lung approximately kidney] > [heart approximately skin approximately muscle] > [fat approximately bone marrow] > [liver approximately bone approximately blood]. In marked contrast to previous results with i.a. cyclosporin A infusion, only a minimal regional advantage of local FK506 delivery (mean right/left concentration ratios 1.0-1.4) was obtained in all forearm tissues over the dose range studied. For each limb tissue, left-sided FK506 concentrations significantly correlated with systemic blood levels, and the left-sided tissue-to-whole-blood concentration ratio did not vary significantly with dose. We conclude that FK506 is pharmacokinetically inferior to cyclosporin A for continuous i.a. administration to the vascularly isolated rabbit forelimb, and hypothesize that this difference is the result of differences in the distribution of each drug within whole blood. Our findings suggest that, despite its demonstrated efficacy in experimental and clinical transplantation, FK506 would not be an appropriate immunosuppressant to deliver via the i.a. route for prevention of limb allograft rejection.