Periostin is induced by IL-4/IL-13 in dermal fibroblasts and promotes RhoA/ROCK pathway-mediated TGF-ß1 secretion in abnormal scar formation.

Excess scar formation can occur after skin injurふy and lead to abnormal scar formation, such as keloids and hypertrophic scars, which are characterised by substantial deposition of extracellular matrix in the dermis. Periostin, an extracellular matrix protein that plays a crucial role in skin development and maintaining homeostasis, is also involved in skin disorders such as systemic/limited scleroderma, wound closure, and abnormal scar formation. However, the mechanism of periostin involvement in abnormal scar formation is not yet fully understood. In this study, we investigated the mechanism by which periostin is involved in abnormal scar formation. Treatment of human dermal fibroblasts (HDFs) with IL-4 and IL-13, which are cytokines of Th2 type immune responses that are up-regulated in abnormal scars, dramatically elevated the levels of periostin mRNA and protein, and also promoted the secretion of periostin by HDFs. Transforming growth factor-ß1 (TGF-ß1) had the same effect on HDFs as IL-4 and IL-13. Stimulation of HDFs with periostin promoted RhoA/ROCK pathway-mediated TGF-ß1 secretion from HDFs. Our results suggest that IL-4 and IL-13 induce periostin expression and secretion, and in turn, secreted periostin induces RhoA/ROCK pathway-mediated TGF-ß1 secretion. Secreted TGF-ß1 then induces further periostin production and secretion, thereby promoting abnormal scar formation.

Immediate tracheal reconstruction with forearm flap and bone graft.

BACKGROUND: "Window" resection of the trachea is sometimes performed to remove tumors invading the trachea. Here, we present a novel reconstructive procedure to this end. METHODS: Eleven patients (mean age, 64 years; range, 46-80 years) were included. Primary diagnoses included thyroid cancer and adenoid cystic carcinoma of the trachea. All defects were partial and located in the neck (mean width and length, 3/5 circle and 7.5 rings; range, 1/2-2/3 circle and 5-9 rings). Immediate 2-stage reconstruction was performed using a forearm flap and free bone graft. The bone graft was utilized as a supportive skeleton. A tracheostoma was left open for several months following the initial surgery, and then closed. RESULTS: The mean flap size was 6.1 × 9.7 cm (range, 6-7 × 7-16 cm). Mean number of grafted bone strips and length were 1.6 (range, 1-3) and 6.1 cm (range, 4.5-7 cm). All flaps survived. Five patients developed complications in the neck, including surgical site infections (SSIs), recurrent nerve palsy, and lymphorrhea. Four patients developed donor site complications, including clavicular fracture and SSIs. Mean postoperative follow-up lasted 85 months (range, 11-149 months). Normal speech was restored in 9 patients. Stoma closure was abandoned in 2 patients, because 1 patient showed vocal cord fixation with advanced age and the other showed bone graft loss following SSI. CONCLUSIONS: Creating a tracheostoma during the first operation prevents postoperative airway compromise. Our bone graft placement easily achieves tracheal rigidity. This procedure is simple and safe for tracheal window defect repair.

Salvage Treatment of Failed Free Jejunal Flap Transfer: Our Experiences and Literature Review.

BACKGROUND: Although there have been many reports on the success of free jejunal flap transfer for pharyngoesophageal reconstruction, reports on salvage procedures for failed transfers remain sparse. In this report, we retrospectively reviewed our salvage procedures for failed jejunal transfers and previous articles describing salvage treatment in failed jejunal flap cases. METHODS: This report includes 6 cases of failed jejunal flap transfer, leading to necessary salvage surgery. We reviewed all cases to examine salvage procedures and early postoperative complications such as fistula formation. We also assessed postoperative late complications and swallowing function during long-term follow-up. A review of the literature was performed via PubMed. RESULTS: Rejejunal transfer was performed successfully in 3 of 6 cases. Gastric pull-up reconstruction was adopted in 2 cases. In 1 case, an external stoma was created because of the patient's poor medical condition. All 3 cases of rejejunal transfer and 1 gastric pull-up case recovered to resuming a normal diet. However, 1 gastric pull-up case required supplemental feeding with a jejunostomy tube. We reviewed 6 articles describing salvage treatment in failed jejunal flap cases. CONCLUSION: When free jejunal transfer fails, rejejunal transfer is optimal. However, in cases that lack suitable recipient vessels or have infection, a second jejunal transfer should not be considered. In such cases, gastric pull-up or colon interposition may be an alternative because they do not require vascular anastomosis. Pedicled pectoralis major flap is also an alternative, although the risk of salivary fistulas is very high.

Shaping a Flap Using a Bioabsorbable Mold-A Preliminary Report.

BACKGROUND: We previously reported that good surgical outcomes can be obtained with breast mold made by 3-dimensional printing. However, detailed breast shape is often difficult to create. Accordingly, we aimed to determine whether transplanting a flap and bioabsorbable mold in vivo would yield better results by retaining the flap shape inside the mold during the scar formation period. METHODS: Vascularized adipose flaps were elevated in the bilateral inguinal region of male Sprague-Dawley rats (n = 7). A cone-shaped, bioabsorbable mold (LactoSorb mesh) was created using a template. On the experimental side, the flap was inserted into the mold and fixed. On the control side, a conical flap was created using absorbable sutures, based on a template. RESULTS: The flaps were harvested 3 months postoperatively, and flap volume, base area, and projection were measured with 3-dimensional imaging. Volume and base area on the mold side tended to be smaller than those on the control side (P = 0.18 and 0.13, respectively) and close to the values of the template. In addition, the ratio of projection and base area value was significantly greater on the mold side than on the control side (P = 0.04). Histology revealed little inflammatory cell invasion, and scar tissue thickness around the flap showed no significant difference between the 2 groups (P = 0.76). CONCLUSIONS: This study demonstrated that soft-tissue morphology can be controlled to some extent with a bioabsorbable mold. Its clinical application in breast reconstruction requires further investigation.

Cutaneous resurfacing around a permanent tracheostoma with an internal mammary artery perforator flap.

When soft tissue reconstruction near a permanent tracheostoma is needed, transfer of a thin and pliable flap is preferable in order to avoid occlusion of the newly created tracheostomal opening. Although microsurgical fasciocutaneous flap transfer may be desirable for such reconstruction, it is not always an option due to lack of recipient vessels for vascular anastomosis or a patient's poor medical condition that would prohibit a lengthy procedure. An alternative option is the internal mammary artery perforator flap, which is easy to elevate, has a long arc of rotation, and has a reliable blood supply. Here, we report three cases of cutaneous resurfacing around a permanent tracheostoma with an internal mammary artery perforator flap.

Free jejunal flap transfer containing multiple vascular pedicles for pharyngoesophageal reconstruction in conjunction with anterior mediastinal tracheostomy.

BACKGROUND: When pharyngoesophagectomy is performed in conjunction with anterior mediastinal tracheostomy, reconstructing both the trachea and alimentary tract is extremely difficult. We developed a novel 1-stage reconstructive procedure using a single free jejunal flap containing multiple vascular pedicles to decrease postoperative morbidity and mortality. Free jejunal flap transfer with multiple vascular pedicles could offer a viable option for reducing associated life-threatening complications. METHODS: We performed a retrospective review of 34 patients who underwent free jejunal flap transfer with multiple vascular pedicles in anterior mediastinal tracheostomy and pharyngoesophagectomy due to lesions involving both the airway and esophagus. In all cases, 1-stage reconstruction of the digestive tract and trachea was performed. Technical details and outcomes were analyzed. RESULTS: All 34 jejunal flaps (100%) survived. Major morbidity classified as Clavien-Dindo grades III and IV occurred in 10 (29.4%) and 0 (0%) patients, respectively during hospitalization. With regard to common complications, anastomotic leakage from transferred jejunal flaps and surgical site infections occurred in 0 (0%) and 7 (20.6%) patients, respectively. Five (14.7%) patients experienced tracheal stoma dehiscence. Donor site morbidity was observed in 2 (5.9%) patients. The overall in-hospital mortality rate was 2.9%. CONCLUSIONS: Our 1-stage reconstruction procedure achieved low morbidity and low mortality rates following anterior mediastinal tracheostomy and pharyngoesophagectomy. Only 1 jejunal flap transfer is needed to simultaneously reconstruct the trachea and alimentary tract in a safe and reliable manner with this procedure.

Hydroxyapatite implantation for the repair of a congenital nasal anomaly: 10 years follow-up.

Frontonasal dysplasia is a rare congenital anomaly characterized by ocular hypertelorism, a broad nasal root, and vertical median cleft of the nose and/or upper lip and palate. We report a case of frontonasal dysplasia in which hydroxyapatite was used to treat a nasal deformity in early childhood. In the 10 years of follow-up of our case, there were no complications such as infection, malpositioning, or exposure, and computed tomography revealed no resorption or malpositioning of the implant. Hydroxyapatite implants may be a viable alternative to autologous bone/cartilage grafts for the repair of congenital nasal anomalies until nasal development is completed.

Efficacy of STRATAFIX in Inframammary Fold Recreation in Autologous Breast Reconstruction.

Supplemental Digital Content is available in the text.

Free Flap Survival Despite Internal Jugular Vein Thrombosis in Head and Neck Reconstruction.

Microvascular free tissue transfer is one of the most common techniques of reconstruction for complex head and neck surgical defects. Generally, venous thrombosis is more likely to occur than arterial thrombosis in vascular anastomosis. Thus, recipient veins must be chosen carefully. Although the internal jugular vein is preferred as a recipient vein by many microsurgeons, internal jugular vein thrombosis is a potential complication, as shown in our report. Therefore, we consider that the external jugular vein still is an option as a recipient for venous anastomosis and that it is better to perform multiple vein anastomoses with 2 different venous systems, such as the internal and external jugular systems, than anastomoses within the same venous system.

STRATAFIX for Abdominal Wall Repair following Abdominal Flap Harvest.

Supplemental Digital Content is available in the text.

DIEP Flap Breast Reconstruction in Patients with Breast Ptosis: 2-Stage Reconstruction Using 3-Dimensional Surface Imaging and a Printed Mold.

BACKGROUND: Autologous breast reconstruction can be performed for breasts with ptosis to a certain extent, but if patients desire to correct ptosis, mastopexy of the contralateral breast is indicated. However, accurate prediction of post-mastopexy breast shape is difficult to make, and symmetrical breast reconstruction requires certain experience. We have previously reported the use of three-dimensional (3D) imaging and printing technologies in deep inferior epigastric artery perforator (DIEP) flap breast reconstruction. In the present study, these technologies were applied to the reconstruction of breasts with ptosis. METHODS: Eight breast cancer patients with ptotic breasts underwent two-stage unilateral DIEP flap breast reconstruction. In the initial surgery, tissue expander (TE) placement and contralateral mastopexy are performed simultaneously. Four to six months later, 3D bilateral breast imaging is performed after confirming that the shape of the contralateral breast (post-mastopexy) is somewhat stabilized, and a 3D-printed breast mold is created based on the mirror image of the shape of the contralateral breast acquired using analytical software. Then, DIEP flap surgery is performed, where the breast mold is used to determine the required flap volume and to shape the breast mound. RESULTS: All flaps were engrafted without any major perioperative complications during both the initial and DIEP flap surgeries. Objective assessment of cosmetic outcome revealed that good breast symmetry was achieved in all cases. CONCLUSIONS: The method described here may allow even inexperienced surgeons to achieve reconstruction of symmetrical, non-ptotic breasts with ease and in a short time. While the requirement of two surgeries is a potential disadvantage, our method will be particularly useful in cases involving TEs, i.e., delayed reconstruction or immediate reconstruction involving significant skin resection.

Infectious Complications following Breast Reconstruction Using Tissue Expanders in Patients with Atopic Dermatitis.

Infectious complications represent one of the most prominent factors contributing to tissue expander (TE) loss in breast reconstruction procedures. Several patient characteristics that increase the risk for surgical-site infection or TE infection have been reported, but no study has focused on the relationship between atopic dermatitis (AD) and TE infection or surgical-site infection. Recently, we investigated 203 cases of breast reconstruction surgeries performed using TEs and noted that all 3 patients who had AD developed infectious complications that ultimately led to TE removal. Considering its pathophysiology, it is likely that patients with AD relatively easily develop infectious complications due to barrier dysfunction, abnormalities in innate immune responses, or colony formation by Staphylococcus aureus. Particular caution should be exercised for breast reconstruction using man-made materials in cases complicated by AD.

Endothelial cell-derived endothelin-1 is involved in abnormal scar formation by dermal fibroblasts through RhoA/Rho-kinase pathway.

Hypertrophic scars and keloids are characterized by excessive dermal deposition of extracellular matrix due to fibroblast-to-myofibroblast differentiation. Endothelin-1 (ET-1) is primarily produced by vascular endothelial cells and plays multiple roles in the wound-healing response and organ fibrogenesis. In this study, we investigated the pathophysiological significance of ET-1 and involvement of RhoA, a member of the Rho GTPases, in hypertrophic scar/keloid formation. We found that ET-1 expression on dermal microvascular endothelial cells (ECs) in hypertrophic scars and keloids was higher than that in normal skin and mature scars. We also confirmed that ET-1 induced myofibroblast differentiation and collagen synthesis in cultured human dermal fibroblasts through the RhoA/Rho-kinase pathway. Finally, since hypertrophic scar/keloid formation was most prominent in areas exposed to mechanical stretch, we examined how mechanical stretch affected ET-1 secretion in human dermal microvascular ECs, and found that mechanical stretch increased ET-1 gene expression and secretion from ECs. Taken together, these results suggest that dermal microvascular ECs release ET-1 in response to mechanical stretch, and thereby contribute to the formation of hypertrophic scars and keloids through the RhoA/Rho-kinase pathway.

A two-tiered structure device based on stereolithography for residual mandible repositioning in mandibular reconstruction with fibular flap.

OBJECTIVE: We invented a two-tiered structure device based on stereolithography for residual mandible repositioning in mandibular reconstruction with fibular flap, and examined its usefulness. PATIENTS AND METHODS: A total of eight patients (six carcinomas and two osteomyelitis) who had undergone mandibular reconstruction with fibular flap were included. Mandibular defects according to Jewer's classification were L for five, LC for two, and H for one patient (range of bone defect size, 7.7-13.3 cm). Based on a stereolithographic mandibular model, a two-tiered structure device was made preoperatively with resin, and was applied during surgery to define the accurate position of residual mandible following segmental mandibulectomy. Postoperative aesthetic and functional outcomes, including dental status, diet, and speech were evaluated. RESULTS: The device was applied without any problems during surgery. Follow-up period ranged from eight to twenty-two months. Good postoperative alignment of the grafts and occlusion were also achieved in all eight patients. Five patients were able to return to eating meals as they had pre-surgery, and two patients required dental rehabilitation with dentures. As for speech, four patients scored ten points, three patients scored eight points, and one patient scored four points in Hirose's scoring system, which means that seven patients was rated as excellent, and one patient was rated as poor. Aesthetic outcomes were excellent in three patients, good in three patients, and fair in two patients. CONCLUSION: Our device was easy to prepare, successfully maintained the precise position of the residual mandible, and facilitated bone graft cutting and insetting during reconstruction. © 2016 Wiley Periodicals, Inc. Microsurgery 37:509-515, 2017.

Divided and Sliding Superficial Temporal Artery Flap for Primary Donor-site Closure.

Superficial temporal artery (STA) flaps are often used for reconstruction of hair-bearing areas. However, primary closure of the donor site is not easy when the size of the necessary skin island is relatively large. In such cases, skin grafts are needed at the donor site, resulting in baldness. We have solved this issue by applying the divided and sliding flap technique, which was first reported for primary donor-site closure of a latissimus dorsi musculocutaneous flap. We applied this technique to the hair-bearing STA flap, where primary donor-site closure is extremely beneficial for preventing baldness consequent to skin grafting. The STA flap was divided into 3, and creation of large flap was possible. Therefore, we concluded that the divided and sliding STA flap could at least partially solve the donor-site problem. Although further investigation is necessary to validate the maximum possible flap size, this technique may be applicable to at least small defects that are common after skin cancer ablation or trauma.

Reconstruction after Excision of Hidradenitis Suppurativa: Are Skin Grafts Better than Flaps?

After surgical excision of hidradenitis suppurativa, reconstruction with a skin graft or a flap is performed when primary closure is not possible. However, the recurrence rate is reportedly high even after wide surgical excision. It is still unclear which reconstruction method provides the lowest recurrence rate. In this report, we present a case of intractable hidradenitis suppurativa in the bilateral perineal region. After wide excision and repair with bilateral groin flaps, a unilateral groin flap was replaced with a split-thickness skin graft because of flap necrosis. Although the skin graft repair region has been recurrence free for 4 years postoperatively, other regions with flap repair showed recurrence 1 year postoperatively, leading to reexcision and repair with a split-thickness skin graft. The current case provides an opportunity to reconsider the optimal surgical strategy for hidradenitis suppurativa. Taking into consideration the fact that hair follicles and sweat glands are involved in the etiology of hidradenitis suppurativa, split-thickness skin grafting, which lack cutaneous appendages, may be superior to flap repair or primary closure in terms of recurrence.

Aesthetic outcomes of inframammary fold recreation in two-stage, implant-based, breast reconstruction.

BACKGROUND: When the inframammary fold (IMF) is excised in mastectomy procedures for oncologic reasons, it must be recreated to restore a natural breast shape. Despite refinements in surgical techniques, postoperative loss of a well-defined IMF can occur. This study aimed to assess the outcomes of IMF recreation after two-stage, implant-based breast reconstruction. METHODS: We retrospectively reviewed 75 consecutive patients who underwent unilateral, two-stage, implant-based breast reconstruction between 2013 and 2015 at the authors' institution. Among them, IMF recreation was performed in 37 patients through a modified Nava's internal method. Aesthetic outcomes of the recreated IMFs were evaluated by observer assessment of two criteria, and critical factors affecting IMF outcomes were also analyzed. RESULTS: We found that contralateral breast ptosis (p < 0.05) and lack of postmastectomy radiotherapy (PMRT, p < 0.01) were significant predictors of better IMF outcomes. Nipple-sparing mastectomy and skin-sparing mastectomy resulted in better IMF outcomes, as compared with non-skin-sparing mastectomy (p < 0.05 for each), while no significant difference was observed between them in patients who did not undergo PMRT (p = 0.19). Similarly, larger implant volume, but not projection of implant, was a predictor of better IMF outcomes when limited to patients who did not undergo PMRT (p < 0.05). Age, body mass index, timing of reconstruction, and extent of overexpansion had no significant effect on IMF outcomes. CONCLUSIONS: Based on these critical factors, the shape of the reconstructed breast and the need for reshaping the contralateral breast can be predicted. Special attention should be paid to patients with non-skin-sparing mastectomy and PMRT. When these patients desire a medium- to large-sized ptotic breast, conversion to autologous reconstruction can achieve symmetrical breast reconstruction.

Differentiated adipose-derived stem cells promote the recovery of nociceptor function in rats.

The loss of nociceptive function in the skin because of trauma or surgery can impair the quality of life. The recovery of nociceptor function is mediated by two different axonal responses: nerve growth factor (NGF)-dependent collateral sprouting of undamaged nerves and NGF-independent regeneration of damaged nerves. We reported previously that adipose-derived stem cells (ASCs) can transdifferentiate into Schwann cell (SC)-like cells (dASCs) and that transplantation of dASCs increases axonal density in skin flaps. In the present study, we used an animal model that allowed for the individual assessment of collateral sprouting and regeneration. In-vitro differentiation of ASCs to dASCs significantly increased the production of NGF and brain-derived neurotrophic factor (BDNF) to levels comparable with SCs. In-vivo experiments showed that dASC and SC transplantation significantly increased the area of the mechano-nociceptive field in both collateral sprouting and regeneration models, whereas ASC transplantation exerted no significant effect. Antibody blocking experiment showed that these effects of dASC transplantation in the regeneration model were partly mediated by BDNF. Interestingly, the final areas of nociceptive fields between the two experimental models did not differ significantly for any treatment condition. These results indicate that dASC transplantation differentially facilitates collateral sprouting and axonal regeneration by delivering NGF and other neurotrophic factors (e.g. BDNF), respectively. Although there is a limit to nociceptive field enlargement irrespective of axonal response, dASC transplantation could present a new approach for improving nociceptive function in denervated skin.