Sensate Reverse Medial Plantar Flap for Reliable Forefoot Reconstruction with Flow-through Anterolateral Thigh Flap.

A reverse medial plantar flap is a major option for reconstructing the plantar forefoot. However, reconstruction of the distal forefoot stretches the vessels, causing tightness, and the skin graft to the donor site adds pressure to the vessel, precipitating venous congestion. We used a reverse medial plantar flap to reconstruct the lateral distal forefoot with a flow-through of the anterolateral thigh (ALT) flap for donor site coverage to maintain physiological and stable blood flow. A 74-year-old woman presented to our hospital with a 20-year history of left forefoot skin tumor. The tumor was resected, and histological examination revealed porocarcinoma in the cystic poroid hidradenoma. Additional excision was performed, and the defect area was covered with a biodegradable artificial dermis. The skin defect of the lateral distal plantar area was reconstructed with a reverse medial plantar flap with a reverse flow Y-V pedicle extension method, and the donor site was reconstructed with an ALT flap interposing the lateral circumflex femoral artery with the transected posterior tibial artery. The flap was completely engrafted without any complications, including arterial ischemia or venous congestion, during or after surgery. A distally based reverse medial plantar flap with a reverse flow Y-V pedicle extension method and flow-through of the ALT flap should be considered for the reconstruction of the lateral distal forefoot with a large defect. This method can maximize flap extension and maintain stable arterial inflow and venous drainage without the major complications of venous congestion.

A Three-dimensionally Printed Acrylonitrile Butadiene Styrene Model for the Reduction of Nasomaxillary Fracture.

The successful reduction of a nasomaxillary fracture was performed using a three-dimensional printed model. A 16-year-old boy was struck in the left orbit by a baseball; subsequently, he was diagnosed with the nasal bone fracture at a hospital, and was referred to the authors' department. A left nasomaxillary fracture and nasal bone fracture were diagnosed by computed tomography. Standard triangulated language data for the mirror image of the frontal process of the right maxilla were obtained from digital imaging and communications in medicine data for preparing a three-dimensional printed acrylonitrile butadiene styrene model. On postinjury day 13, the frontal process fracture was reduced via transconjunctival and intraoral approaches. After the reduction of the fracture, an absorbable plate fitting to the shape of three-dimensional printed acrylonitrile butadiene styrene model was molded, and the maxillary frontal process and infraorbital rim were reduced and fixed with an absorbable plate and screws. Postoperative computed tomography demonstrated a favorable reduction. The intraoperative use of the 3D printed acrylonitrile butadiene styrene model was helpful in the nasomaxillary fracture reduction and fixation.

"Elephant-trunk" negative pressure wound therapy for fixing artificial dermis with basic fibroblast growth factor for critical limb ischemia.

INTRODUCTION: The treatment of intractable toe ulcer with critical limb ischemia (CLI) is a challenge because of its poor blood flow and the wound. Here, a novel fixation technique for artificial dermis with negative pressure wound therapy (NPWT) was reported. METHOD: After the amputation of toe, artificial dermis made of collagen-gelatin sponge (CGS) was grafted onto the wound where human recombinant basic fibroblast growth factor (bFGF) was sprayed. The foot was put on adhesive iodine-impregnated drape, the artificial-dermis area was covered with a sponge dressing of which another end reached to the drape, and the vacuum port was applied on the dressing sponge sandwiched with two drapes and connected to an NPWT system. Since the shape of sponge-dressing was similar to that of elephant-trunk, the technique in this study was named an "Elephant-trunk" technique. RESULT: During NPWT period, no complications such as air leakage, skin erosion, ischemic around tissue were confirmed. The artificial dermis was engrafted completely at one week after surgery, and the wound was confirmed to close completely. CONCLUSION: This NPWT technique with bFGF and CGS accelerated the healing of wound treated conservatively with artificial dermis in CLI patients.

Superficial Temporal Artery Pseudoaneurysm following Midface Thread-lift.

Facial thread-lifting has been popular because of its ease and safety with short down time. However, many physicians perform the procedure in cosmetic clinics, which can result in several complications. This report describes the surgical treatment of iatrogenic superficial temporal artery pseudoaneurysm (STAP) following thread-lifting. A 27-year-old man developed a painless, pulsating soft mass in the pre-auricular region after undergoing a thread-lift in a private cosmetic clinic 3 months before being referred to the authors' hospital. The mass was diagnosed as a STAP, using magnetic resonance imaging. The pseudoaneurysm was resected completely, and the superficial temporal artery was microsurgically reconstructed. Although there are some surgical procedures for treating STAP, such as surgical resection and embolization, the former is considered the first choice. Physicians should be trained before performing thread-lifting and must know the possibility of an iatrogenic STAP appearing after the procedure and the face and neck anatomy to prevent complications.

Comparison of contraction among three dermal substitutes: Morphological differences in scaffolds.

Various kinds of synthetic dermal substitutes are produced and used in clinical application and contribute to wound bed preparation for subsequent skin grafting. Although their appearance and outcomes are different, the criteria for the selection of proper synthetic dermal substitutes is not well defined yet. In this study, we focused on the contraction of dermal substitutes and compared the morphological differences in scaffolds. A marked contraction was observed with Pelnac® compared to Integra® and Terudermis® in vitro. We also showed that the pore size of Pelnac® was smaller than that of Integra® and Terudermis®. The shape of the pore was oval in Pelnac®, whereas those in Integra® and Terudermis® were more circular. Differences in the morphological structure may have affected the contraction of the synthetic dermal substitutes.

The use of laser Doppler imaging as a predictor of burn depth and hypertrophic scar postburn injury.

Hypertrophic scarring (HTS) is a fibroproliferative disorder that commonly develops after severe burn injuries. Overexpression of transforming growth factor-ß (TGF-ß) by an increased number of fibrocytes has been associated with increased extracellular matrix molecule expression leading to HTS. The most widely accepted adjuvant to clinical assessment of burn depth is laser Doppler imaging (LDI) and may predict injury to the dermis that corresponds to cellular and molecular changes associated with HTS. A prospective, blinded, control trial was performed comparing LDI and clinical assessment for the decision to operate. Immunohistochemistry and real-time reverse transcription polymerase chain reaction was performed to determine whether there is a correlation between histological assessment of burn depth and LDI, and the presence of fibrocytes was detected using confocal microscopy. The positive predictive value for a burn requiring a graft was calculated to be >90%. Immunohistochemistry on biopsy samples revealed an increased expression of TGF-ß, connective tissue growth factor, heat shock protein 47, and collagen type I in deep burn wounds compared to superficial burns. Using the fibrocyte-specific markers procollagen type I and lymphocyte-specific protein-1, there was an increased number of fibrocytes in deep burn areas compared to superficial burn. In deep burn injuries, increased infiltration of fibrocytes occurs leading to an overexpression of TGF-ß1 and connective tissue growth factor. More importantly, LDI was >90% accurate at predicting the need for excision and grafting. The accuracy of the decision to debride deep dermal burns to avoid HTS using both clinical parameters and LDI was supported by histological and biochemical measurements.

Impaired cutaneous wound healing in transforming growth factor-ß inducible early gene1 knockout mice.

Transforming growth factor-ß inducible early gene (TIEG) is induced by transforming growth factor-ß (TGF-ß) and acts as the primary response gene in the TGF-ß/Smad pathway. TGF-ß is a multifunctional growth factor that affects dermal wound healing; however, the mechanism of how TGF-ß affects wound healing is still not well understood because of the complexity of its function and signaling pathways. We hypothesize that TIEG may play a role in dermal wound healing, with involvement in wound closure, contraction, and reepithelialization. In this study, we have shown that TIEG1 knockout (TIEG1-/-) mice have a delay in wound closure related to an impairment in wound contraction, granulation tissue formation, collagen synthesis, and reepithelialization. We also found that Smad7 was increased in the wounds and appeared to play a role in this wound healing model in TIEG1-/- mice.

Stromal cell-derived factor 1 (SDF-1) and its receptor CXCR4 in the formation of postburn hypertrophic scar (HTS).

Recent data support the involvement of stromal cell-derived factor 1 (SDF-1) in the homing of bone marrow-derived stem cells to wound sites during skeletal, myocardial, vascular, lung, and skin wound repair as well as some fibrotic disorders via its receptor CXCR4. In this study, the role of SDF-1/CXCR4 signaling in the formation of hypertrophic scar (HTS) following burn injury and after treatment with systemic interferon α2b (IFNα2b) is investigated. Studies show SDF-1/CXCR4 signaling was up-regulated in burn patients, including SDF-1 level in HTS tissue and serum as well as CD14+ CXCR4+ cells in the peripheral blood mononuclear cells. In vitro, dermal fibroblasts constitutively expressed SDF-1 and deep dermal fibroblasts expressed more SDF-1 than superficial fibroblasts. Lipopolysaccharide increased SDF-1 gene expression in fibroblasts. Also, recombinant SDF-1 and lipopolysaccharide stimulated fibroblast-conditioned medium up-regulated peripheral blood mononuclear cell mobility. In the burn patients with HTS who received subcutaneous IFNα2b treatment, increased SDF-1/CXCR4 signaling was found prior to treatment which was down-regulated after IFNα2b administration, coincident with enhanced remodeling of their HTS. Our results suggest that SDF-1/CXCR4 signaling is involved in the development of HTS by promoting migration of activated CD14+ CXCR4+ cells from the bloodstream to wound sites, where they may differentiate into fibrocyte and myofibroblasts and contribute to the development of HTS.

Small leucine-rich proteoglycans, decorin and fibromodulin, are reduced in postburn hypertrophic scar.

Small leucine-rich proteoglycans (SLRPs) are extracellular matrix molecules that regulate collagen fibrillogenesis and inhibit transforming growth factor-ß activity; thus, they may play a critical role in wound healing and scar formation. Hypertrophic scarring is a dermal form of fibroproliferative disorders, which occurs in over 70% of burn patients and leads to disfigurement and limitations in function. By understanding the cellular and molecular mechanisms that lead to scarring after injury, new clinical therapeutic approaches can by developed to minimize abnormal scar formation in hypertrophic scarring and other fibroproliferative disorders. To study the expression and localization of SLRPs with connective tissue cells in tissue immunohistochemistry, immunofluorescence staining, immunoblotting, and reverse-transcription polymerase chain reaction were used in normal skin and hypertrophic scar (HTS). In normal skin, there was more decorin and fibromodulin accumulation in the superficial layers than in the deeper dermal layers. The levels of decorin and fibromodulin were significantly lower in HTS, whereas biglycan was increased when compared with normal skin. There was an increased expression of biglycan, fibromodulin, and lumican in the basement membrane and around basal epithelial cells. In contrast, these proteoglycans were absent or weakly expressed in HTS. The findings suggest that down-regulation of SLRPs after wound healing in deep injuries to the skin plays an important role in the development of fibrosis and HTS.

Toll-like receptors expressed by dermal fibroblasts contribute to hypertrophic scarring.

Hypertrophic scar (HTS), a fibroproliferative disorder (FPD), complicates burn wound healing. Although the pathogenesis is not understood, prolonged inflammation is a known contributing factor. Emerging evidence suggests that fibroblasts regulate immune/inflammatory responses through toll-like receptor 4 (TLR4) activated by lipopolysaccharide (LPS) through adaptor molecules, leading to nuclear factor kappa-light-chain-enhancer of activated B cells and mitogen-activated protein kinases activation, cytokine gene transcription and co-stimulatory molecule expression resulting in inflammation. This study explored the possible role of TLR4 in HTS formation. Paired normal and HTS tissue from burn patients was collected and dermal fibroblasts isolated and cultured. Immunohistochemical analysis of tissues demonstrated increased TLR4 staining in HTS tissue. Quantitative RT-PCR of three pairs of fibroblasts demonstrated mRNA levels for TLR4 and its legend myeloid differentiation factor 88 (MyD88) in HTS fibroblasts were increased significantly compared with normal fibroblasts. Flow cytometry showed increased TLR4 expression in HTS fibroblasts compared with normal. ELISA demonstrated protein levels for prostaglandin E2, interleukin (IL)-6, IL-8 and monocyte chemotactic protein-1 (MCP-1) were significantly increased in HTS fibroblasts compared to normal. When paired normal and HTS fibroblasts were stimulated with LPS, significant increases in mRNA and protein levels for MyD88, IL-6, IL-8, and MCP-1 were detected. However, when transfected with MyD88 small interfering RNA (siRNA), then stimulated with LPS, a significant decrease in mRNA and protein levels for these molecules compared to only LPS-stimulated fibroblasts was detected. In comparison, a scramble siRNA transfection did not affect mRNA or protein levels for these molecules. Results demonstrate LPS stimulates proinflammatory cytokine expression in dermal fibroblasts and MyD88 siRNA eliminates the expression. Therefore, controlling inflammation and manipulating TLR signaling in skin cells may result in novel treatment strategies for HTS and other FPD.

Bladder outlet obstruction: progression from inflammation to fibrosis.

OBJECTIVE: To investigate the progression of urodynamic changes, as well as histological and biochemical outcomes over a prolonged period of partial bladder outlet obstruction (pBOO) in an animal model with physiologically relevant pBOO. MATERIALS AND METHODS: Healthy, adult, female Fischer rats underwent surgical creation of a pBOO for either 2, 4, 8, or 13 weeks and were compared with sham-operated rats. Urodynamic measurements were used to compare bladder volumes and pressure. Tissue was grossly analysed with light microscopy and bladder weights and thicknesses were compared. Reverse transcription-polymerase chain reaction for collagen, transforming growth factor ß (TGF-ß), connective tissue growth factor (CTGF), hypoxia inducible factor 1α (HIF-1α), and platelet-derived growth factor (PDGF-A) was performed on all samples, as well as immunohistochemistry (IHC) for α-smooth muscle actin (α-SMA). Finally, mass spectrometry was used to quantify the collagen content of the bladders as a measure of fibrosis. RESULTS: After induction of pBOO, all rats remained healthy. Initial urodynamics showed an increase in capacity while maintaining normal pressures, but then deteriorated into small capacity, high-pressure bladders. Haematoxylin and eosin (H&E) staining showed an initial inflammatory response, and this was confirmed with significantly increased mRNA levels of TGF-ß, CTGF, HIF-1α, and PDGF. The progression to smooth muscle hypertrophy was evident on H&E and confirmed with increased bladder mass and thickness. IHC for α-SMA showed a progressive increase associated with the elevated bladder pressures. Masson's trichrome and mass spectrometry showed a progressive increase in collagen to 13 weeks. CONCLUSION: With this model, we have effectively replicated the clinical scenario, with significant pathophysiological changes occurring insidiously in otherwise healthy rats. We believe that our observed changes represent distinct phases of bladder decompensation; with an initial inflammatory response to the stress of the pBOO, smooth muscle hypertrophy to overcome the increased urethral resistance, and eventual decompensation to fibrosis. The time course of the inflammatory markers implies the need for early intervention to prevent this cascade. Novel strategies targeting these observed physiological responses could lead to improved preventative strategies, with respect to biochemical pathways and the time course of their initiation.

Scar and contracture: biological principles.

Dysregulated wound healing and pathologic fibrosis cause abnormal scarring, leading to poor functional and aesthetic results in hand burns. Understanding the underlying biologic mechanisms involved allows the hand surgeon to better address these issues, and suggests new avenues of research to improve patient outcomes. In this article, the authors review the biology of scar and contracture by focusing on potential causes of abnormal wound healing, including depth of injury, cytokines, cells, the immune system, and extracellular matrix, and explore therapeutic measures designed to target the various biologic causes of poor scar.

Treatment of facial angiofibroma of tuberous sclerosis using cultured epithelial autografts.

Treatment of facial angiofibroma of tuberous sclerosis is problematic, because the skin lesions involve entire dermis. Five patients aged from 14 to 33 (mean: 23.6) years old with angiofibroma of tuberous sclerosis were treated with cultured epithelial autografts between 1995 and 2004. The entire area of the facial lesions was excised using a razor to remove large nodules, and then the remaining lesions were further abraded to a rather deep layer of the dermis to smooth the skin and remove small nodules. Then a cultured autologous epithelium was grafted onto the wound. In all patients, epithelization was complete within 10 (mean: 9) days after the surgery. All patients were followed up for more than 6 months and showed neither depigmentation due to scar formation nor hypertrophic scars. In some patients, some pebbly regrowth had occurred at 5 years postoperatively, but the appearance was quite acceptable.

Novel application method of artificial dermis: one-step grafting procedure of artificial dermis and skin, rat experimental study.

BACKGROUND: Currently, to treat skin defects with artificial dermis (AD), two surgical procedures where the artificial dermis grafting and another secondary skin grafting are required. The purpose of this study was to achieve simultaneous grafting of the artificial dermis and the split-skin. To enhance the wound angiogenesis, cultured endothelial cells, fibroblasts and PDWHF (platelet derived wound healing factor) were employed. METHODS: The experiment consists of following two parts: (1) Investigation to obtain faster angiogenesis into the bilayer artificial dermis: full-thickness wounds created on the back of the rats were treated with the artificial dermis (Terudermis, with silicone sheet, TERUMO Co., Japan). Prior to the artificial dermis grafting, following four groups were established; control group (AD alone, n=6), PDWHF group (AD treated with PDWHF, n=6), cultured cells group (AD treated with cultured endothelial cells and fibroblasts, n=6), combination group (AD treated with PDWHF and cultured cells, n=6). (2) Trial of one-stage grafting of the AD and the skin: simultaneous grafting of the artificial dermis and skin was performed using the same rat model. Before making skin defects, split thickness skin were harvested. Then the skin grafting was carried out immediately after the AD grafting. To allow grafting of the skin onto the artificial dermis, the AD without silicone sheet (Terudermis without silicone sheet, TERUMO Co., Japan) were used. Two groups, control group (AD alone, n=3) and treatment group (AD with PDWF and cultures, n=3) were established. RESULTS: (1) When the artificial dermis were treated with PDWHF, cultured endothelial cells and fibroblasts, vascular invasion into the artificial dermis was observed 5 days after the surgery. (2) In the treatment group, the skin grafted immediately after the artificial dermis grafting was completely taken. CONCLUSIONS: The present study revealed that treatment with PDWHF, combined with cultured endothelial cells and fibroblasts, accelerated wound angiogenesis. By this method, one-step grafting procedure of the artificial dermis and the skin is possible.

Treatment of phacomatosis pigmentovascularis: a combined multiple laser approach.

BACKGROUND: Phacomatosis pigmentovascularis (PPV) consists of a capillary malformation with a variety of melanocytic lesions, which involve various regions of the body and are difficult to treat with conventional therapeutic tools. OBJECTIVE: We described two cases with PPV (type IIa and IIb) that were successfully treated with different lasers. METHODS: The areas involved by both melanocytic lesions and port-wine stains were treated using the Q-switched ruby laser, the Q-switched Alexandrite laser, and the flashlamp pumped pulsed-dye laser. RESULTS: Removal of a good portion of cutaneous and vascular lesions using combined multiple laser approach was achieved after 6 sessions in the first case under general anesthesia and after 31 sessions under local anesthesia in the second case. CONCLUSION: PPV type II can be treated successfully by laser treatment. We prefer to start combined multiple laser treatment of PPV in childhood period under general anesthesia because it will reduce the number of treatment, improve the patient's quality of life, and increase the cost-effectiveness of the treatment.