Published papers

Background Medium-sized to giant congenital melanocytic naevi (CMN) are difficult to treat, especially if the lesions appear on the face or extremities where treated areas are visible and cosmesis is important. Objectives In infants, nests of pigmented naevus reside more superficially and the skin is more transparent than in adults, so we treated medium-sized to giant CMN with early serial Q-switched ruby laser therapy from infancy. Patients and methods We treated nine patients with medium-sized to giant CMN on the face or upper limbs from 1 month of age with early serial Q-switched ruby laser therapy. The laser power was initially 5 J cm) 2 and increased in 0 5 J cm) 2 steps to a maximum of 10 J cm) 2. There were three treatment sites on the forehead, one on the temple, one on the cheek and four on the upper arm. Results It took 8-15 treatments for the CMN to become a colour similar to the surrounding skin. The mean number of treatments was 9 6. The colour was reduced to 0-20% of the colour of the baseline lesion in all nine patients. Partial slight repigmentation occurred in eight of these patients. These naevi were treated with an additional one or two Q-switched ruby laser irradiations and successfully lightened for at least 1 year. In the remaining patient, pigmentation returned to a level similar to the original lesion within 1 month of the last treatment. Therefore, the lesion was excised for cosmetic reasons. After the treatment series, the skin texture was fine and no patients had hypertrophic scarring. Conclusions Although treatment of one patient with the Q-switched ruby laser therapy failed, the remaining patients responded well and had good to excellent skin texture without hypertrophic scarring. Early serial Q-switched ruby laser treatment, starting from infancy, is a promising treatment method for this condition.

Background: Mono-L-aspartyl chlorin e6 (Talaporfin sodium) is a novel photosensitizer, and is currently being used in photodynamic therapy for various malignant tumors in combination with irradiation with a 664 nm laser. An interesting characteristic of Talaporfin sodium is that the skin photosensitivity after injection of this agent disappears faster than any other existing photosensitizers. This study examined the vascular events that occurred postirradiation in the chicken comb as a capillary malformation model after photosensitization with Talaporfin sodium. Materials and Methods: A single intravenous bolus injections of Talaporfin sodium was administered to the chickens, and a 1 cm diameter area of the comb of each animal was irradiated with a 664 nm visible red laser. The gross changes in the chicken combs were recorded for 7-14 days after photodynamic therapy. For the histological examination, HE, PTAH and Azan stained sections were analyzed. Results: All treated chicken combs had blanched after photodynamic therapy. Microscopy demonstrated an absence of erythrocytes and the vessel lumina were obliterated, leaving the normal overlying epidermis completely intact. Concomitantly with selective destruction of the capillaries in the target area, moderate invasion of inflammatory cells and a slight increase in the stroma were observed. Conclusions: In the chicken comb model, photodynamic therapy with Talaporfin sodium effectively achieved selective destruction of the microvasculature while leaving the epidermis intact. Our results strongly suggest that photodynamic therapy with Talaporfin sodium could be a feasible method to treat dermal hypervascular lesions.

Matrix metalloproteinases (MMPs) have been implicated in wound healing. To analyze the roles of MMP-9 and MMP-13 in wound healing, we generated full-thickness cutaneous wounds in MMP-9 knockout (KO), MMP-13 KO, MMP-9/13 double KO, and wildtype mice. Macroscopic wound closure was delayed in all of the KO mice, as compared with wild-type mice. The rate of re-epithelialization was significantly delayed in MMP-9 KO and MMP-13 KO mice and remarkably delayed in MMP-9/13 double KO mice, as compared with wild-type mice. Both MMP-9 and MMP-13 were expressed by the leading edges of epidermal cells in wild-type mice, and the migration of keratinocytes was suppressed by treatment with an MMP inhibitor or transfection of small interfering RNAs for MMP-9 or MMP-13, as compared with controls. The vascular density in wound granulation was significantly lower in both MMP-13 KO and MMP-9/13 double KO mice than in wild-type mice. Degradation of connective tissue growth factor in wound tissue was transiently prevented in MMP-13 KO mice. Morphometric analyses demonstrated a reduction in both wound contraction and myofibroblast formation in both MMP-13 KO and MMP-9/13 double KO mice. Proliferation and transforming growth factor-β1-induced myofibroblast differentiation of dermal fibroblasts from MMP-13 KO mice were decreased, as compared with wild-type dermal fibroblasts. These data suggest that MMP-13 plays a role in keratinocyte migration, angiogenesis, and contraction in wound healing, while MMP-9 functions in keratinocyte migration.

Various modifications of the gluteus maximus musculocutaneous flap have been reported. Among them, the split gluteus maximus musculocutaneous flap is easy to prepare and does not leave ambulatory insuffiency. However, the safety of extending the skin portion beyond the margin of the muscle has not yet been clarified. Angiography was performed systemically on 11 fresh cadavers, and the distance the margin of the gluteus maximus muscle could be extended was observed. Based on these anatomical data, reconstruction after total skin resection of perianal and lower gluteal hidradenitis suppurativa was performed with an extended split superior gluteal maximus musclocutaneous flap. Surgery was performed on three sides of two patients. From the anatomical results, we found that it is possible to extend the flap beyond the iliac crest several centimetres superiorly, and to the gluteal fold inferiorly, and several centimetres laterally. We designed the flap such that the extended area is situated in these areas. All flaps took well and did not show any congestion or necrosis. There were no recurrences at least 1 year after surgery. When reconstructing the lower part of the buttock, an extended split superior gluteus maximus musclocutaneous flap is easy to raise and leaves aesthetically satisfactory results. Thus it may be the first choice for reconstruction of the lower buttock.

The study goals were to demonstrate the superior laryngeal artery in detail with angiograms and to understand its vasculature three-dimensionally. Three fresh cadavers were totally injected with lead oxide-gelatin mixture. The larynx with the surrounding tissue was resected and radiographed stereoscopically with soft X ray system. We get informed consent from a person in question and the bereaved family. The superior laryngeal artery was divided into the ascending and descending branches. The ascending branch supplied the epiglottis chiefly from the ventral surface, and anastomosed with branches of the lingual artery. The descending branch supplied the vestibular and vocal folds, muscles of the larynx and mucosa over the muscles, and anastomosed with distal branches of the superior thyroid artery. Stereographic angiograms and macroscopic observation enabled us to understand vasculature of the superior laryngeal artery.

Background: Although skin grafting after resection of the hidradenitis suppurativa is frequently used, the contour after skin grafting is unsatisfactory. We studied four patients who suffered from severe gluteal hidradenitis suppurativa and needed total skin resection of the affected lesion. Methods: Reconstruction after total skin resection was performed with fasciocutaneous (FC) flaps of three different designs based on an arterial anatomical study: an island V-Y advancement flap based on the descending branch of the inferior gluteal artery; a rotation V-Y advancement flap based on the first perforator of the deep femoral artery and the descending branch of the inferior gluteal artery; and, a bilobed flap at each lobe containing either the descending branch or medial branch of the inferior gluteal artery. The flap designs were decided from the size and the location of the skin defect. Results: The contours after reconstruction were satisfactory and did not experience any recurrence of hidradenitis suppurativa for at least 1 year after operation. Conclusion: We showed three different designs of FC flaps to cover the gluteal skin defects based on the anatomical study. FC flaps may be chosen for reconstruction after resection of perianal hidradenitis suppurativa.

We combined a sternomastoid musculocutaneous (SMC) flap and an external jugular veno-accompanying-artery adipofascial (EJ VAF) flap, for head and neck defect reconstruction. The SMC flap provides a rich arterial flow and the EJ VAF flap good venous drainage, making a reliable flap easy-to-raise combination. The flap took well in two patients requiring head and neck reconstruction.

Rectangular flaps on the rat or mouse dorsum are frequently used for flap survival elongation research. However, since rectangular flaps are purely random, the survival rate varies among individuals. A reliable animal flap model with low individual variation is desirable for flap survival research, especially in the angiogenic field. We investigated the survival rate of paired flaps in the rat dorsum containing 3 vascular territories in each flap, and determined their usefulness for flap elongation research. Two symmetrical adjoining rectangular flaps (11×3 cm each) were drawn on the rat dorsum. Two days after material injection, flaps were elevated with only the deep circumflex iliac vessels as the vascular pedicle. Flaps were immediately sutured back and the flap survival area was measured 7 days after the operation. The control group (n = 9) had saline solution injected in both flaps. The bone marrow group (n = 8) had bone marrow injected in the right flap, and saline solution injected in the left flap. In the control group, the survival rate of the paired flaps was not statistically different (right flap, 89.0±5.6%; left flap, 89.3±4.5%). In the bone marrow group, the survival rate between the bone marrow injected flap (89.9±3.7%), and the saline flap (84.8±4.3%) was statistically different. The rat dorsal paired island skin flap model shows low difference in flap survival rate and uses an internal control. This is a suitable model for flap survival elongation research.

Background: Giant congenital nevocellular nevi (GCNN) are histologically characterized by the broad distribution of nevus cells in the epidermis and dermis. Objective: To characterize E-cadherin in GCNN and define its role in nevic cell migrations. Methods: Twenty-four cases were immunohistochemically examined and in five cases cells were isolated for primary culture for migration assays. Results: The nevus cells in the superficial region showed the immunoreactivity of E-cadherin in a membranous pattern, but those in the deep part of dermis had little immunoreactivity. Ultra-structural analysis of the superficial nevus cells revealed that E-cadherin immunodeposits in the fibrillar processes around the cell body in a spotted pattern. This distribution pattern is quite different from that in the adherens junction of skin squamous epithelial cells. Boyden chamber experiments were performed using primary cultures of intradermal nevus cells. EDTA pretreatment reduced cell migration to the E-cadherin positive side when the E-cadherin positive population was relatively large in the primary cultures. Conclusions: These results indicate that E-cadherin in the nevus cells may affect nevus cell motility rather than intercellular attachment.

To meet tissue requirements for oxygen, capillaries must be properly distributed without excess or shortage. In this process, tissue oxygen concentration is well known to determine capillary density via the hypoxia-induced cascade, in which HIFs and VEGF play key roles. However, some additional mechanisms modulating this cascade are suggested to be involved in precise capillary network formation. Here, we showed that leukemia inhibitory factor (LIF) was predominantly expressed in developing endothelium, while its receptor was expressed in surrounding cells such as retinal astrocytes. The retinas of Lif-/- mice displayed increased microvessel density accompanied by sustained tip cell activity, due to increased VEGF expression by astrocytes in the vascularized area. Lif-/- mice resisted hyperoxygen insult in the oxygen-induced retinopathy model, whereas they paradoxically had increased numbers of neovascular tufts. In an in vitro study, LIF inhibited hypoxia-induced VEGF expression and proliferation in cultured astrocytes. Lif-/- mice also exhibited similarly increased microvessel density and upregulated VEGF in various tissues outside the retina. Together, these findings suggest that tissues and advancing vasculature communicate to ensure adequate vascularization using LIF as well as oxygen, which suggests a new strategy for antiangiogenic therapy in human diseases such as diabetic retinopathy and cancer.

When moving a local flap, a dog ear sometimes appears at the base of the flap. If we try to correct the dog ear primarily, the blood supply to the flap may be disturbed. In such a case, the dog ear is prone to be corrected secondarily. In the present report we show a new technique for correcting a dog ear that enables correction to be done primarily and sufficiently. The principle of the technique is to de-epithelialise the dog ear portion and dig it in to the dermis to preserve the subdermal plexus at the base of the flap intact. This method is useful especially at the base of a transposition flap because the pedicle tends to be narrowed by the conventional correction.

Background: Curettage and dermabrasion are effective in treating giant congenital melanocytic naevi (GCMN). We report two patients with rapid, severe postoperative repigmentation. To the best of our knowledge this is the first report on the histological features of such patients. Objectives: We wish to call attention to histological features that may cause rapid, severe repigmentation after curettage and dermabrasion of medium to giant CMN. Patients/methods: From 1998 to 2002, we treated 23 patients with medium to giant CMN with curettage and dermabrasion. Patients being treated ranged in age from 1 month to 19 years. Histological samples were taken from the centre of naevi in all patients during surgery. Histological types were 12 intradermal and 11 compound. Follow-up after curettage lasted at least 3 years. Results: Among our 23 patients only two showed repigmentation soon after surgery. Histological sections from these two patients indicated naevoid cells in the deep dermis along hair follicles or sebaceous glands. However, no such pigmented naevoid cells along hair follicles were observed in samples from patients successfully treated with curettage and dermabrasion with less repigmentation. Conclusions: Although we saw only two cases of repigmentation soon after curettage and dermabrasion, we suspect a correlation between pigmented naevoid cells around hair follicles and repigmentation. If histological sections of skin biopsies show pigmented cells along hair follicles in the deep dermis, other treatments such as total skin resection followed by skin grafting or tissue expansion may be better choices than curettage or dermabrasion.

In reconstruction of the extremities, a distally based flap is useful for covering the distal parts. Distally based flaps are, however, prone to congestion in the peripheral part of the flap, followed by partial necrosis because of insufficient venous drainage caused by resistance of the venous valves. To rescue peripheral congestion of the distally based flap, venous anastomosis is effective so that the venous blood flows in the direction of the venous valve. We applied this idea to a patient who had skin defects around the knee after a wide resection of the skin tumor, and covered them with a distally based greater saphenous venoadipofascial-sartorius muscle combined flap. The whole area of the flap took well without congestion after anastomosis of the vein.