There has been a long-standing need for guidelines on the diagnosis and treatment of keloids and hypertrophic scars that are based on an understanding of the pathomechanisms that underlie these skin fibrotic diseases. This is particularly true for clinicians who deal with Asian and African patients because these ethnicities are highly prone to these diseases. By contrast, Caucasians are less likely to develop keloids and hypertrophic scars, and if they do, the scars tend not to be severe. This ethnic disparity also means that countries vary in terms of their differential diagnostic algorithms. The lack of clear treatment guidelines also means that primary care physicians are currently applying a hotchpotch of treatments, with uneven outcomes. To overcome these issues, the Japan Scar Workshop (JSW) has created a tool that allows clinicians to objectively diagnose and distinguish between keloids, hypertrophic scars, and mature scars. This tool is called the JSW Scar Scale (JSS) and it involves scoring the risk factors of the individual patients and the affected areas. The tool is simple and easy to use. As a result, even physicians who are not accustomed to keloids and hypertrophic scars can easily diagnose them and judge their severity. The JSW has also established a committee that, in cooperation with outside experts in various fields, has prepared a Consensus Document on keloid and hypertrophic scar treatment guidelines. These guidelines are simple and will allow even inexperienced clinicians to choose the most appropriate treatment strategy. The Consensus Document is provided in this article. It describes (1) the diagnostic algorithm for pathological scars and how to differentiate them from clinically similar benign and malignant tumors, (2) the general treatment algorithms for keloids and hypertrophic scars at different medical facilities, (3) the rationale behind each treatment for keloids and hypertrophic scars, and (4) the body site-specific treatment protocols for these scars. We believe that this Consensus Document will be helpful for physicians from all over the world who treat keloids and hypertrophic scars.

Adult mammalian wounds leave visible scars, whereas skin wounds in developing mouse fetuses are scarless until a certain point in development when complete regeneration occurs, including the structure of the dermis and skin appendages. Analysis of the molecular mechanisms at this transition will provide clues for achieving scarless wound healing. The fibroblast growth factor (FGF) family is a key regulator of inflammation and fibrosis during wound healing. We aimed to determine the expression and role of FGF family members in fetal wound healing. ICR mouse fetuses were surgically wounded at embryonic day 13 (E13), E15, and E17. Expression of FGF family members and FGF receptor (FGFR) in tissue samples from these fetuses was evaluated using in situ hybridization and reverse transcription-quantitative polymerase chain reaction. Fgfr1 was downregulated in E15 and E17 wounds, and its ligand Fgf7 was upregulated in E13 and downregulated in E15 and E17. Recombinant FGF7 administration in E15 wounds suppressed fibrosis and promoted epithelialization at the wound site. Therefore, the expression level of Fgf7 may correlate with scar formation in late mouse embryos, and external administration of FGF7 may represent a therapeutic option to suppress fibrosis and reduce scarring.

Lymphaticovenular anastomosis (LVA) is a widely performed surgical procedure for the treatment of lymphedema. For good LVA outcomes, identifying lymphatic vessels and venules is crucial. Photoacoustic lymphangiography (PAL) is a new technology for visualizing lymphatic vessels. It can depict lymphatic vessels at high resolution; therefore, this study focused on how to apply PAL for lymphatic surgery. To visualize lymphatic vessels, indocyanine green was injected as a color agent. PAI-05 was used as the photoacoustic imaging device. Lymphatic vessels and veins were visualized at 797- and 835-nm wavelengths. First, it was confirmed whether the branching of the vasculature as depicted by the PAL was consistent with the actual branching of the vasculature as confirmed intraoperatively. Second, to use PAL images for surgical planning, preoperative photoacoustic images were superimposed onto the patient limb through augmented reality (AR) glasses (MOVERIO Smart Glass BT-30E). Lymphatics and venule markings drawn using AR glasses were consistent with the actual intraoperative images obtained during LVA. To anastomose multiple lymphatic vessels, a site with abundant venous branching was selected as the incision site; and selecting the incision site became easier. The anatomical morphology obtained by PAL matched the surgical field. AR-based marking could be very useful in future LVA.

Interactions between epithelial and dermal cells are essential for hair follicle morphogenesis and maintenance. In experimental trials of hair regeneration, isolated dermal cells have been shown to possess hair‐inducing capacity. However, dermal cells lose this potential immediately after cultivation. Sphere‐forming multipotent cells derived from the dermis possess hair‐inducing capacity. These previous findings raise the question of whether hair‐inducing capacity depends on the identity as dermal cells or the process of sphere formation. To address this issue, we compared the in vitro and in vivo characteristics of two‐dimensionally cultured or thereafter sphere formation–induced dermal and lung mesenchymal cells. We show that sphere‐forming mesenchymal cells exhibited higher expression of Wnt signalling genes. Sphere‐forming cells but not two‐dimensionally cultured cells possessed in vivo hair‐inducing capacity. These data suggest that various mesenchymal cells attain hair‐inducing capacity through the process of sphere formation.

Background Dermal backflow (DBF), which refers to lymphatic reflux due to lymphatic valve insufficiency, is a diagnostic finding in lymphedema. However, the three-dimensional structure of DBF remains unknown. Photoacoustic lymphangiography (PAL) is a new technique that enables the visualization of the distribution of light-absorbing molecules, such as hemoglobin or indocyanine green (ICG), and can provide three-dimensional images of superficial lymphatic vessels and the venous system. This study reports the use of PAL to visualize DBF structures in the extremities of patients with lymphedema after cancer surgery. Methods Patients with a clinical or lymphographic diagnosis of lymphedema who previously underwent surgery for cancer at one of two participating hospitals were included in this study. PAL was performed using the PAI-05 system. ICG was administered subcutaneously in the affected hand or foot, and ICG fluorescence lymphography was performed using a nearinfrared camera system prior to PAL. Results Between April 2018 and January 2019, 21 patients were enrolled and examined using PAL. The DBF was composed of dense, interconnecting, three-dimensional lymphatic vessels. It was classified into three patterns according to the composition of the lymphatic vessels: a linear structure of lymphatic collectors (pattern 1), a network of lymphatic capillaries and lymphatic collectors in an underlying layer (pattern 2), and lymphatic capillaries and precollectors with no lymphatic collectors (pattern 3). Conclusions PAL showed the structure of DBF more precisely than ICG fluorescence lymphography. The use of PAL to visualize DBF assists in understanding the pathophysiology and assessing the severity of cancer-related lymphedema.

Background Lymphaticovenular anastomosis (LVA) is a minimally invasive surgical procedure used to treat lymphedema. Volumetric measurements and quality-of-life assessments are often performed to assess the effectiveness of LVA, but there is no method that provides information regarding postoperative morphological changes in lymphatic vessels and veins after LVA. Photoacoustic lymphangiography (PAL) is an optical imaging technique that visualizes the distribution of light-absorbing molecules, such as hemoglobin or indocyanine green (ICG), and provides three-dimensional images of superficial lymphatic vessels and the venous system simultaneously. In this study, we performed PAL in lymphedema patients before and after LVA and compared the images to evaluate the effect of LVA. Methods PAL was performed using the PAI-05 system in three patients (one man, two women) with lymphedema, including one primary case and two secondary cases, before LVA. ICG fluorescence lymphography was performed in all cases before PAL. Follow-up PAL was performed between 5 days and 5 months after LVA. Results PAL enabled the simultaneous visualization of clear lymphatic vessels that could not be accurately seen with ICG fluorescence lymphography and veins. We were also able to observe and analyze morphological changes such as the width and the number of lymphatic vessels and veins during the follow-up PAL after LVA. Conclusions By comparing preoperative and postoperative PAL images, it was possible to analyze the morphological changes in lymphatic vessels and veins that occurred after LVA. Our study suggests that PAL would be useful when assessing the effect of LVA surgery.