Kanae Ikeda

Resveratrol inhibits fibrogenesis and induces apoptosis in keloid fibroblasts

Keloids are benign dermal fibrotic tumors arising during the wound healing process. The mechanisms of keloid formation and development still remain unknown, and no effective treatment is available. Resveratrol, a dietary compound, has anticancer properties and, from recent studies, it has been suggested that resveratrol may have an antifibrogenic effect on organs such as the liver and kidney. Based on this idea, we investigated its effect on the regulation of extracellular matrix expression, proliferation, and apoptosis of keloid fibroblasts. Type I collagen, α‐smooth muscle actin, and heat shock protein 47 expression decreased in resveratrol‐treated keloid fibroblasts in a dose‐dependent manner. In addition, resveratrol diminished transforming growth factor‐β1 production by keloid fibroblasts. We also demonstrated that it suppressed their proliferation and induced apoptosis of the fibroblasts. Conversely, resveratrol did not decrease type I collagen, α‐smooth muscle actin, and heat shock protein 47 mRNA expression in normal skin fibroblasts and barely suppressed cell proliferation. Our data indicate that resveratrol may have an antifibrogenic effect on keloid fibroblasts without any adversely effects on normal skin fibroblasts, suggesting the potential application of resveratrol for the treatment of keloids.

Fibroblasts induce expression of FGF4 in ovarian cancer stem-like cells/cancer-initiating cells and upregulate their tumor initiation capacity.

Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are defined as a small population of cells within cancer that contribute to cancer initiation and progression. Cancer-associated fibroblasts (CAFs) are stromal fibroblasts surrounding tumor cells, and they have important roles in tumor growth and tumor progression. It has been suggested that stromal fibroblasts and CSCs/CICs might mutually cooperate to enhance their growth and tumorigenic capacity. In this study, we investigated the effects of fibroblasts on tumor-initiating capacity and stem-like properties of ovarian CSCs/CICs. CSCs/CICs were isolated from the ovarian carcinoma cell line HTBoA as aldehyde dehydrogenase 1 high (ALDH1high) population by the ALDEFLUOR assay. Histological examination of tumor tissues derived from ALDH1high cells revealed few fibrous stroma, whereas those derived from fibroblast-mixed ALDH1high cells showed abundant fibrous stroma formation. In vivo tumor-initiating capacity and in vitro sphere-forming capacity of ALDH1high cells were enhanced in the presence of fibroblasts. Gene expression analysis revealed that fibroblast-mixed ALDH1high cells had enhanced expression of fibroblast growth factor 4 (FGF4) as well as stemness-associated genes such as SOX2 and POU5F1. Sphere-forming capacity of ALDH1high cells was suppressed by small-interfering RNA (siRNA)-mediated knockdown of FGFR2, the receptor for FGF4 which was expressed preferentially in ALDH1high cells. Taken together, the results indicate that interaction of fibroblasts with ovarian CSCs/CICs enhanced tumor-initiating capacity and stem-like properties through autocrine and paracrine FGF4-FGFR2 signaling.

Three cases of giant pilomatrixoma – considerations for diagnosis and treatment of giant skin tumours with abundant inner calcification present on the upper body

BACKGROUND Pilomatrixoma frequently occurs as a solitary, small tumour on the face or upper extremities of people younger than 20 years. METHODS We report three cases of giant pilomatrixoma. In all these cases, outward appearances and imaging investigations suggested malignant tumours. Preoperative biopsies suggested that case 1 was a basal cell carcinoma, but cases 2 and 3 had no malignant features on biopsy. Two of the cases experienced rare complications - hypercalcaemia caused by parathyroid-related protein (PTHrP) production and multiple occurrences. RESULTS All three tumours were removed with a 1-3-cm margin. The postoperative histopathologies showed pilomatrixoma in all three cases. CONCLUSIONS Rarely, pilomatrixoma develops to a giant size with various atypical outward appearances consistent with a malignant tumour. Preoperative clinical appearances frequently lead to misdiagnosis, and preoperative examinations are unreliable. Therefore, when a giant tumour with abundant inner calcification is present in a young patient, the possibility of a pilomatrixoma should be considered.

Modified thin abdominal wall flap (glove flap) for the treatment of acute burns to the hands and fingers

BACKGROUND Burns to the dorsum of the fingers and hands require debridement and immediate coverage by skin flap at the earliest opportunity. In such situations, the conventional abdominal wall flap is still commonly used as it is a convenient and safe technique, but the foremost problem with this flap is that it is thick and therefore cosmetically unacceptable; it is also functionally not very suitable as the bulkiness of the digits prevents full range of motion. We have developed a modified thin abdominal flap (glove flap) which attains good results. METHODS Incisions are made in the skin of the abdominal wall only where the hand is to be inserted and where each of the finger tips will be pulled through. The flap is undermined just under the skin to the depth that preserves the subcutaneous vascular networks to create a thin flap. The interdigital area of the flaps should not be undermined so as to create a glove-type pocket. The hand is then inserted in this subcutaneous pocket. After insertion of the injured hand for 10 to 14 days, the flap is resected and attached to the hand. RESULTS Seven hands of 5 patients were treated by this technique and all the flaps survived safely. The function of the hands and fingers, including range of motion (ROM) in each joint, was successfully salvaged. The reconstructed hands and fingers were aesthetically pleasing. CONCLUSIONS Although the abdominal wall flap is not a new technique, our modifications to this flap make it possible to acquire functionally and aesthetically better results. Although many excellent techniques such as perforator flaps have been reported recently, we conclude that the abdominal wall flap is still a very useful technique because it can be performed easily, safely and within a short time.

Reverse facial artery flap from the submental region

BACKGROUND Of all the local flaps that allow elevation of a sufficiently large-sized flap while also leaving an inconspicuous donor-site scar, the submental island flap is frequently used for the reconstruction of a defect in the lower two-thirds of the face. However, this flap has certain disadvantages such as the technique being slightly difficult to perform and, more importantly, that it carries a significant risk of injury to the facial nerve. METHODS Here, we propose the reverse facial artery flap, elevated from the submandibular region. Our method creates a flap that includes only the platysma under the skin island, without either the submental or facial artery. However, above the superior border of the skin island, the flap includes the facial artery along with subcutaneous soft tissue. The blood circulation of the skin island is in a random pattern and that of the subcutaneous pedicle is in an axial pattern. RESULTS Four cases were treated using our method. There were no complications in all four cases, and the results were also cosmetically very good. CONCLUSIONS As compared to the submental island flap, our method is easier to perform and carries a much lower risk of damage to the marginal mandibular branch of the facial nerve, as the facial artery crosses over the facial nerve at only one point. In addition, the method produces a thin flap. Therefore, when considering correction of a small-sized defect in the lower two-thirds of the face, our method has a number of advantages over the submental island flap.

The reverse superficial temporal artery flap from the preauricular region, for the small facial defects

BACKGROUND For the reconstruction of facial defects, the retroauricular flap is generally used. However, this flap has disadvantages, such as venous return disturbance and reddish skin colour peculiar to the retroauricular region. METHODS Here, we report the reverse superficial temporal artery (STA) flap, elevated from the preauricular region. In our method, the flap is retrogradely elevated including the STA under the skin island in the preauricular region and the temporoparietal fascia around the superficial temporal vessels in the temporal region. The donor site is closed primarily or by the retroauricular flap. RESULTS Five cases with a pedicled flap and one case with a free flap were treated using our method. In one case, a minor congestion of the flap occurred postoperatively, and temporary facial nerve palsy in another case. In all cases, the results were cosmetically good, and the scar at the donor site was inconspicuous. CONCLUSIONS As compared to the retroauricular flap, our method is easier to perform and the flap has a reliable blood circulation. Moreover, it can be used with both a pedicled and a free flap, leaving an inconspicuous scar at the donor site, and a colour match without reddish skin. Therefore, when considering reconstruction of small-sized defects on the face, our method is more useful than the retroauricular flap.

The acute surgical management of injury to the helix and antihelix in patients with large body surface area burns.

Deformity or loss of the ear may be caused by superficial dermal burns or deep burns. The depth of ear burns is progressive because the ear protrudes from head and is easily affected by external pressure. Therefore, burn wounds of the ear should be debrided as early as possible, before irreversible changes of the cartilage, and covered with healthy tissue. We describe a surgical procedure for treatment of the extensively burned ear. With this technique, the helix is covered by a postauricular advancement flap, and the antihelix is covered by a skin graft. Because the procedure is straightforward and can be completed within a short time, it can be performed at the same time as other life-saving measures. The use of a skin flap permits adequate debridement in terms of both depth and width, minimising the risk of infection. The helix can be reconstructed to provide a natural appearance, and late ulcer formation due to external irritation is prevented. We have treated 15 ears on 11 patients with this procedure and have consistently obtained a satisfactory outcome.

Reconstruction of a red lip that has a defect in one half, using the remaining red lip

It is difficult to reconstruct the red lip and achieve good functional results such as normal sphincter force, sensitivity and movement of the lip. In addition, it is also difficult to attain colour and texture matches. We reconstruct a red lip that has a defect in one half, using the remaining red lip. Using the technique reported herein, we can achieve excellent functional and aesthetic results. Functionally, sphincter force and sensation recover early and the movement of the lip returns to normal. In addition, the reconstructed lip develops a symmetrical and natural appearance.

Primary reconstruction of the umbilicus, using two rectangular subcutaneous pedicle flaps

thermography provides us the perfect tool to test if the same technique can help us improve free flap surgery. This case supports the case for further research into dynamic thermography to preoperatively image the abdominal wall. It allowed us to non-invasively assess the vasculature, plan surgery, and prepare the patient for a modified operation. One challenge which we currently are investigating solutions for is a reliable method of providing a calibrated scale on the thermographic images so as to allow easy correlation visually, as well as with other imaging modalities such as CT angiography.

Double combined Z-plasty for wide-scar contracture release.

Z-plasty is one of the most widely employed techniques in plastic surgery and mainly serves the following purposes: elongation along the axis of the scar, dispersal of the scar followed by breaking up the straight-line scar and realigning the scar within the lines of minimal tension. It is useful especially to release linear-scar contracture, yet difficult for wide scars. This report describes a novel technique to release contracture effectively for any wide scars using a new design called double combined Z-plasty. The design is simple. The main limb is set to incise the wide scar, and this main limb is shared as a peripheral limb by two other Z-plasty designs. From the main limb, each central limb is designed along the margin of the scar in the opposite direction. The main and central limbs have 90° between them. Other peripheral limbs are then designed facing laterally to the intact skin to make 60° for the central limb. After skin incision, two triangular intact skin flaps could be inserted into the wide scar from both sides, making it possible to release contracture. We performed this technique on eight patients. All wounds healed well and scar contracture was satisfactorily released. This procedure is very useful for wide-scar contracture, compared to conventional Z-plasty.