Naoaki Rikihisa

Port-wine stain (PWS) is a congenital vascular malformation commonly treated with pulsed dye laser (PDL) therapy. PDL exploits selective photothermolysis, in which hemoglobin in red blood cells (RBCs) absorbs laser energy, generating localized heat that induces endothelial damage. However, in microvessels, axial RBC migration creates a hemoglobin-depleted cell-free layer along the vessel walls, reducing laser efficacy. Hemoglobin vesicles (HbVs)—nano-sized artificial RBCs—distribute uniformly within these layers, offering the potential to enhance hemoglobin distribution and laser absorption. To investigate the impact of HbV administration on PDL therapy, a three-dimensional numerical model of human skin tissue containing vascular networks was developed. Monte Carlo simulations were used to evaluate laser absorption, and thermal conduction analysis was performed to compute temperature distributions and estimate thermal damage via the Arrhenius model. Two conditions were considered: Case 1 (without HbV administration) and Case 2 (with HbV administration). In Case 2, HbV administration increased optical absorption in vessel walls and enhanced thermal damage, particularly in subpapillary vessels. The threshold energy fluence required to induce irreversible thermal damage was reduced, and heat flux at the upper vessel walls was elevated. These findings indicate that HbV administration enhances the homogeneity and efficacy of PDL-induced vascular damage, potentially allowing effective treatment at lower energy fluences while minimizing off-target tissue injury. The study provides a theoretical basis for optimizing PDL parameters in PWS therapy and underscores the potential of patient-specific treatment protocols using artificial blood substitutes.

We devised a surgical tape that prevents skin tears while maintaining adhesive strength. Under the assumption that microscopic damage to the skin is reflected in pain felt on the skin, we statistically analyzed skin pain when the tape was peeled off to show the skin protection effect of the mesh on the new tape. This tape has a three-layer structure consisting of a tape substrate, adhesive, and mesh. When the tape is applied to the skin, a mesh is located between the adhesive and the skin. The adhesive contacts the skin through the mesh holes and fixes the substrate to the skin; it does not come into contact with the skin at the mesh body; therefore, the adhesive-skin contact area is reduced. In this experiment, we used surgical tape with and without mesh. At 8 hours after the application of each tape to the forearm of five adult males, it was removed. All tapes were peeled off while maintaining an angle of approximately 120° between the skin and tape substrate. For the tape with mesh, the tape substrate was peeled off in two ways: peeling off the substrate together with the mesh and peeling off the substrate, leaving the mesh on the skin. A perception and pain quantification analyzer (Pain Vision™) was used to quantify pain. The data were compared and examined statistically (Friedman’s test and Wilcoxon’s coded rank test). The least pain was experienced while peeling off the tape substrate, leaving the mesh on the skin. There was a significant difference in pain levels among the three tape removal methods. There was also a significant difference between the two peeling methods in the experimental group. The skin protection effect of the mesh reduced pain when the surgical tape was removed.

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Artificial red blood cells (i.e. hemoglobin [Hb] vesicles [Hb‐Vs]) function effectively as photosensitizers in flashlamp‐pumped pulsed‐dye laser (PDL) treatment for port‐wine stains in animal models. Hb‐Vs deliver more Hb to the vicinity of the endothelial cells. Both Hb‐Vs and red blood cells absorb the laser energy and generate heat, supporting the removal of very small blood vessels and deeper subcutaneous blood vessels with PDL irradiation in in vivo experiments. Here, we analyzed the photosensitizing effect of Hb‐Vs in PDL irradiation on large blood vessels and surrounding soft tissues. We histopathologically analyzed markers of damage to the large vessels and surrounding dermal tissue in a rabbit auricle model following PDL irradiation alone or subsequent to the addition of intravenous Hb‐V injection. Markers were graded on a five‐point scale and statistically compared. The changes in laser light absorption and reflection in a human skin model caused by the administration of Hb‐Vs were evaluated using Monte Carlo light‐scattering programs. Histological markers of damage to blood vessels were significantly greater in Hb‐V‐injected arteries and veins measuring 1–3 mm in diameter as compared with the controls. However, Hb‐V injection significantly reduced PDL‐induced necrosis and hemorrhage in the surrounding tissues. During computer simulation, photon absorption increased within the vessel layer and decreased around the layer. Intravenous Hb‐Vs increase the extent of damage in larger vessel walls but significantly reduce damage to the surrounding skin after subsequent PDL irradiation. These beneficial effects are the result of improving vessel selectivity by Hb‐Vs in vessels. Hb‐V administration prior to PDL irradiation therapy could mechanically improve the outcomes and safety profiles of port‐wine stain treatment protocols.

The objective was to prepare guidelines to perform the current optimum treatment by organizing effective and efficient treatments of hemangiomas and vascular malformations, confirming the safety, and systematizing treatment, employing evidence-based medicine (EBM) techniques and aimed at improvement of the outcomes. Clinical questions (CQs) were decided based on the important clinical issues. For document retrieval, key words for literature searches were set for each CQ and literature published from 1980 to the end of September 2014 was searched in Pubmed, Cochrane Library, and Japana Centra Revuo Medicina (JCRM). The strengths of evidence and recommendations acquired by systematic reviews were determined following the Medical Information Network Distribution System (MINDS) technique. A total of 33 CQs were used to compile recommendations and the subjects included efficacy of resection, sclerotherapy/embolization, drug therapy, laser therapy, radiotherapy, and other conservative treatment, differences in appropriate treatment due to the location of lesions and among symptoms, appropriate timing of treatment and tests, and pathological diagnosis deciding the diagnosis. Thus, the Japanese Clinical Practice Guidelines for Vascular Anomalies 2017 have been prepared as the evidence-based guidelines for the management of vascular anomalies.

Our previous study proposed using artificial blood cells (hemoglobin vesicles, Hb-Vs) as photosensitizers in dye laser treatment for port-wine stains (PWSs). Dye laser photons are absorbed by red blood cells (RBCs) and hemoglobin (Hb) mixture, which potentially produce more heat and photocoagulation and effectively destroy endothelial cells. Hb-Vs combination therapy will improve clinical outcomes of dye laser treatment for PWSs because very small vessels do not contain sufficient RBCs and they are poor absorbers/heaters of lasers. In the present study, we analyzed the relationship between vessel depth from the skin surface and vessel distraction through dye laser irradiation following intravenous Hb-Vs injection using a chicken wattle model. Hb-Vs were administered and chicken wattles underwent high-energy irradiation at energy higher than in the previous experiments. Hb-Vs location in the vessel lumen was identified to explain its photosensitizer effect using human Hb immunostaining of the irradiated wattles. Laser irradiation with Hb-Vs can effectively destroy deep vessels in animal models. Hb-Vs tend to flow in the marginal zone of both small and large vessels. Increasing laser power combined with Hb-Vs injection contributed for deep vessel impairment because of the synergetic effect of both methods. Newly added Hb tended to flow near the target endothelial cells of the laser treatment. In Hb-Vs and RBC mixture, heat transfer to endothelial cells from absorbers/heater may increase. Hb-Vs function as photosensitizers to destroy deep vessels within a restricted distance that the photon can reach.

We suggest a novel method that uses artificial blood cells (hemoglobin vesicles, Hb-Vs) as photosensitizers in dye laser treatment (at 595-nm wavelength) for port-wine stains (i.e., capillary malformations presenting as red birthmarks) based on the results of animal experiments. As compared with human red blood cells, Hb-Vs have the same absorbance of 595 nm wavelength light and produce the same level of heat following dye laser irradiation. Small sized Hb-Vs (250 nm) distribute in the plasma phase in blood and tend to flow in the marginal zone of microvessels. Intravenous injections of Hb-Vs caused the dilatation of microvessels, and dye laser treatment with Hb-Vs destroyed the vessel wall effectively. Following the intravenous injection of Hb-Vs, the microvessels contained more Hb that absorbed laser photons and produced heat. This extra Hb tended to flow near the endothelial cells, which were the target of the laser treatment. These attributes of Hb-Vs will potentially contribute to enhancing the efficacy of dye laser treatment for port-wine stains. Hemoglobin is a type of porphyrin. Thus, our proposed treatment may have aspects of photodynamic therapy using porphyrin that leads to a cytotoxicity effect by active oxygen.

Background: Early excision and skin grafting are commonly used to treat deep dermal burns (DDBs) of the dorsum of the hand. Partial-thickness debridement (PTD) is one of the most commonly used procedures for the excision of burned tissue of the dorsum of the hand. In contrast, full-thickness debridement (FTD) has also been reported. However, it is unclear whether PTD or FTD is better. Methods: In this hospital-based retrospective study, we compared the outcomes of PTD followed by a medium split-thickness skin graft (STSG) with FTD followed by a thick STSG to treat a DDB of the dorsum of the hand in Japanese patients. To evaluate postoperative pigmentation of the skin graft, quantitative analyses were performed using the red, green, and blue (RGB) and the hue, saturation, and brightness (HSB) color spaces. We have organized the manuscript in a manner compliant with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement. Results: Data from 11 patients were analyzed. Six hands (five patients) received grafts in the PTD group and eight hands (six patients) received grafts in the FTD group. Graft take was significantly better in the FTD group (median 98 %, interquartile range 95–99) than in the PTD group (median 90 %, interquartile range 85–90) (P < 0.01). Quantitative skin color analyses in both the RGB and HSB color spaces showed that postoperative grafted skin was significantly darker than the adjacent control area in the PTD group, but not in the FTD group. Conclusions: There is a possibility that FTD followed by a thick STSG is an option that can reduce the risk of hyperpigmentation after surgery for DDB of the dorsum of the hand in Japanese patients. Further investigation is needed to clarify whether the FTD or the thick STSG or both are the factor for the control of hyperpigmentation.