Demographic review of aesthetic surgery for patients with facial palsy.

BACKGROUND: This study analyzed the demographic characteristics of patients with facial palsy who were treated using either dynamic or static procedures. This study aimed to compare the frequency of procedure implementation and age distribution between the two groups. METHODS: This study retrospectively analyzed the medical records of patients treated for facial palsy at a single institution from 2014 to 2022. Among cases included in our study, dynamic procedures involved cross-facial nerve graft and latissimus dorsi or gracilis muscle flap transfer. Static procedures included gold weight insertion, canthopexy, browlift, and thread lift/static slings. RESULTS: Among the 31 patients included in our study, eight (25.8%) incorporated dynamic techniques, and the average age of patients was 44.75 years (range, 24-68 years) with a male to female ratio of 1:4. The remaining 23 patients (74.2%) underwent a static procedure, of which the average age was 59.17 years (range, 23-81 years) which was statistically significantly higher than the average age of 44.75 of dynamic patients (p= 0.013). Regarding the timing of treatment after diagnosis, no patient underwent dynamic procedures more than 20 years after initial diagnosis. A greater diversity in the timing of treatment was observed in the static group. All patients who underwent dynamic procedures were treated using static procedures during the study period. CONCLUSION: Because aesthetics-based static techniques are typically quick outpatient procedures that can be performed under local anesthesia, our study shows that these are often preferred treatments for all age groups, especially for debilitated or older patients. Further research is required to investigate the long-term functional outcomes of these surgical techniques in a wider population of patients.

Open Reduction of an Isolated Anterior Nasal Spine Fracture: A Case Report and Review of the Literature.

A 14-year-old girl had a midfacial trauma event caused by hitting against an opening door and experienced discomfort and swelling of the columella and upper lip. Physical examination revealed mild tenderness on light palpation without any discomfort with upper lip movement. A computed tomography scan of the maxillofacial bones with three-dimensional reconstruction showed a fracture of the anterior nasal spine with obvious leftward displacement, mild-deviation of the caudal aspect of the nasal septum, and no sign of nasal bone fracture. Open reduction and internal fixation was performed with regard to aesthetic and functional concerns, including nasal septum deviation. The postoperative course was uneventful, and healing proceeded normally without complications. Herein, we emphasize the importance of differential diagnosis of isolated anterior nasal spine fractures in patients with midfacial trauma and clinicians' strategic decision-making in treatment modalities.

Breast Tissue Reconstruction Using Polycaprolactone Ball Scaffolds in a Partial Mastectomy Pig Model.

BACKGROUND: Breast cancer patients suffer from lowered quality of life (QoL) after surgery. Breast conservancy surgery (BCS) such as partial mastectomy is being practiced and studied as an alternative to solve this problem. This study confirmed breast tissue reconstruction in a pig model by fabricating a 3-dimensional (3D) printed Polycaprolactone spherical scaffold (PCL ball) to fit the tissue resected after partial mastectomy. METHODS: A 3D printed Polycaprolactone spherical scaffold with a structure that can help adipose tissue regeneration was produced using computer-aided design (CAD). A physical property test was conducted for optimization. In order to enhance biocompatibility, collagen coating was applied and a comparative study was conducted for 3 months in a partial mastectomy pig model. RESULTS: In order to identify adipose tissue and fibroglandular tissue, which mainly constitute breast tissue, the degree of adipose tissue and collagen regeneration was confirmed in a pig model after 3 months. As a result, it was confirmed that a lot of adipose tissue was regenerated in the PCL ball, whereas more collagen was regenerated in the collagen-coated Polycaprolactone spherical scaffold (PCL-COL ball). In addition, as a result of confirming the expression levels of TNF-a and IL-6, it was confirmed that PCL ball showed higher levels than PCL-COL ball. CONCLUSION: Through this study, we were able to confirm the regeneration of adipose tissue through a 3-dimensional structure in a pig model. Studies were conducted on medium and large-sized animal models for the final purpose of clinical use and reconstruction of human breast tissue, and the possibility was confirmed.

Fabrication of 3D-Printed Implant for Two-Stage Ear Reconstruction Surgery and Its Clinical Application.

PURPOSE: Ear reconstruction is one of the most difficult areas in the field of reconstructive surgery. Due to limitations of the current practice, a novel method of auricular reconstruction is needed. Major advancements in three-dimensional (3D) printing technique have rendered the process of ear reconstruction more favorable. Herein, we present our experience in designing and clinically using 3D implants in both 1st and 2nd stage ear reconstruction surgery. MATERIALS AND METHODS: After obtaining 3D CT data from each patient, a 3D geometric ear model was created using mirroring and segmentation processes. The 3D-printed implant design resembles but does not exactly match the normal ear shape, and can be inserted in harmony with the currently used surgical technique. The 2nd stage implant was designed to minimize dead space and support the posterior ear helix. The 3D implants were finally fabricated with a 3D printing system and used in ear reconstruction surgery in our institute. RESULTS: The 3D implants were manufactured for application to the currently used two-stage technique while maintaining the shape of the patient's normal ear. The implants were successfully used for ear reconstruction surgery in microtia patients. A few months later, the 2nd stage implant was used in the 2nd stage operation. CONCLUSION: The authors were able to design, fabricate, and apply patient-specific 3D-printed ear implants for 1st and 2nd stage ear reconstruction surgeries. This design, combined with 3D bioprinting technique, may be a future alternative for ear reconstruction.

The Study of a Validated Assessment Scale for a Localized Submental Fat Volume.

BACKGROUND: This aim of this study was to develop an objective tool for rating submental fat applied to Koreans. METHODS: The study was conducted between April 2019 and October 2019. A total of 92 subjects were enrolled in the study. Clinical photos of the subjects were categorized using validated CR-SMFRS by three plastic surgeons and one dermatologist. The categorized photos were then shown to six different plastic surgeons for evaluation. RESULTS: The Cohen's kappa value for the six raters were 0.830, 0.742, 0.703, 0.907, 0.862, and 0.793 with statistical significance (p < 0.001). ICC value was between 0.860 and 0.966 (p < 0.001). Since the Cohen's value and ICC were above 0.6 for all raters, the ratings performed by all six raters were used in the analysis. The ICC values between raters were between 0.899 and 0.902. CONCLUSIONS: We came up with a set of reference photos that can be used for submental fat rating scale applicable to Korean subjects. LEVEL OF EVIDENCE: II.

Complications Including Capsular Contracture in Direct-to-Implant Breast Reconstruction With Textured Anatomical Versus Smooth Round Implants: A Single Center Retrospective Analysis.

PURPOSE: Implant-based breast reconstruction is the most common reconstruction method used after mastectomy in breast cancer patients. Many studies have compared the smooth round implants and textured anatomical implants. This study aimed to compare the complications, including capsular contracture, between these two implants used in direct-to-implant (DTI) breast reconstruction. METHODS: This retrospective chart review was performed using a prospectively maintained database from a single center. We identified patients who underwent mastectomy with DTI single-stage breast reconstruction at our hospital between August 2011 and June 2021. The overall complications, including capsular contracture, postoperative infection, seroma, hematoma, implant rupture, implant exposure, rippling, implant malposition, and nipple necrosis, were analyzed. RESULTS: In total, 340 breasts of 323 patients were reconstructed by the DTI approach using either textured anatomical (n = 203) or smooth round (n = 137) implants. The incidence of overall complications and capsular contracture was significantly lower with smooth round implants than with textured anatomical implants. Multivariate analysis showed that smooth round implants were associated with a reduced risk of overall complications (odds ratio [OR], 0.465; 95% confidence interval [CI], 0.265-0.813) and capsular contracture (OR, 0.475; 95% CI, 0.235-0.962). Particularly, smooth round implants were associated with a decreased risk of overall complications in patients not receiving adjuvant chemotherapy and a decreased risk of capsular contracture in patients with body mass index < 25 kg/m² and in those not receiving adjuvant radiotherapy. CONCLUSION: Smooth round implants demonstrated a decreased risk of overall complications and capsular contracture when compared with textured anatomical implants. These results may be utilized in counseling patients regarding the advantages and disadvantages of smooth round implants in DTI breast reconstruction.

Association between Immediate Breast Reconstruction and the Development of Breast Cancer-Related Lymphedema.

BACKGROUND: With the increasing number of patients undergoing immediate breast reconstruction after mastectomy, the impact of immediate breast reconstruction on the risk of breast cancer-related lymphedema has become an emerging area of interest. This study aimed to identify the association between immediate breast reconstruction and postoperative lymphedema. METHODS: A retrospective cohort study was conducted from 2006 to 2016 with 5900 consecutive patients who underwent mastectomy for primary breast cancer with or without immediate breast reconstruction. After excluding patients with synchronous contralateral breast cancer, lymphedema before mastectomy, history of procedures performed in the axillary region, and follow-up data of less than 1 year, the cumulative incidence of lymphedema after immediate breast reconstruction and after no reconstruction was calculated and compared using multivariate Cox regression analysis. RESULTS: Overall, 5497 patients (mean age, 51.7 years) were included, and 630 developed lymphedema. The 5-year cumulative incidence rate of lymphedema was significantly reduced in patients who underwent immediate breast reconstruction versus control patients (9.6% versus 12.2%; P = 0.02). In the multivariate analysis, immediate breast reconstruction status (hazard ratio, 0.75; 95% confidence interval, 0.56 to 0.99; P = 0.042) was an independent predictor for lymphedema. Similar significant associations were observed in the subgroup analyses of patients with a body mass index less than 30 kg/m2 (P = 0.024), in those with fewer than 10 dissected lymph nodes (P = 0.042), or in those with adjuvant radiotherapy (P = 0.048). CONCLUSIONS: Immediate breast reconstruction was associated with a reduced risk of lymphedema. These results may be used for predicting the development of lymphedema following breast reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

Cranioplasty and temporal hollowing correction with a three-dimensional printed bioresorbable mesh and double vertical suture anchor muscle sling: a case report.

Postoperative temporal hollowing is a common complication of craniotomy. Damage and repositioning of the temporalis muscle can lead to a depression in the temporal side of the skull with inferior bulging, worsening aesthetic outcomes. We report a case of cranioplasty with three-dimensional (3D) printed mesh involving an additional correction using a temporalis muscle sling to help address this problem. A 3D-printed bioabsorbable mesh was prepared based on preoperative facial computed tomography, and was fixed to the hollowed area for tissue augmentation. The temporalis muscle was elevated and fanned out to its original position, and a sling was attached to a screw that was fixed to the mesh. For reinforcement, an additional sling was attached to another screw fixed to the mesh 2-3 cm vertically above the first screw. Aesthetic results were confirmed immediately after surgery and later during outpatient follow-up. Both depression and lateral bulging were resolved, and there was no delayed drooping of the temporalis muscle on 6-month follow-up. There were no complications, and the patient was satisfied with the appearance. This is a simple yet effective technique with a low risk of complications, and should be considered for postoperative temporal hollowing patients, especially those with severe lateral bulging.

Breast Tissue Restoration after the Partial Mastectomy Using Polycaprolactone Scaffold.

As breast conserving surgery increases in the surgical treatment of breast cancer, partial mastectomy is also increasing. Polycaprolactone (PCL) is a polymer that is used as an artifact in various parts of the human body based on the biocompatibility and mechanical properties of PCL. Here, we hypothesized that a PCL scaffold can be utilized for the restoration of breast tissue after a partial mastectomy. To demonstrate the hypothesis, a PCL scaffold was fabricated by 3D printing and three types of spherical PCL scaffold including PCL scaffold, PCL scaffold with collagen, and the PCL scaffold with breast tissue fragment were implanted in the rat breast defect model. After 6 months of implantation, the restoration of breast tissue was observed in the PCL scaffold and the expression of collagen in the PCL scaffold with collagen was seen. The expression of TNF-α was significantly increased in the PCL scaffold, but the expression of IL-6 showed no significant difference in all groups. Through this, it showed the possibility of using it as a method to conveniently repair tissue defects after partial mastectomy of the human body.

Effect of Mortalin on Scar Formation in Human Dermal Fibroblasts and a Rat Incisional Scar Model.

Wound healing is a complicated cascading process; disequilibrium among reparative processes leads to the formation of pathologic scars. Herein, we explored the role of mortalin in scar formation and its association with the interleukin-1α receptor using in vitro and in vivo models. To investigate the effects of mortalin, we performed an MTT cell viability assay, qRT-PCR, and Western blot analyses, in addition to immunofluorescence and immunoprecipitation studies using cultured fibroblasts. A rat incisional wound model was used to evaluate the effect of a mortalin-specific shRNA (dE1-RGD/GFP/shMot) Ad vector in scar tissue. In vitro, the mortalin-treated human dermal fibroblast displayed a significant increase in proliferation of type I collagen, α-smooth muscle actin, transforming growth factor-ß, phospho-Smad2/3-complex, and NF-κB levels. Immunofluorescence staining revealed markedly increased mortalin and interleukin-1α receptor protein in keloid tissue compared to those in normal tissue, suggesting that the association between mortalin and IL-1α receptor was responsible for the fibrogenic effect. In vivo, mortalin-specific shRNA-expressing Ad vectors significantly decreased the scar size and type-I-collagen, α-SMA, and phospho-Smad2/3-complex expression in rat incisional scar tissue. Thus, dE1-RGD/GEP/shMot can inhibit the TGF-ß/α-SMA axis and NF-κB signal pathways in scar formation, and blocking endogenous mortalin could be a potential therapeutic target for keloids.

Robotic DIEP Flap Harvest through a Totally Extraperitoneal Approach Using a Single-Port Surgical Robotic System.

SUMMARY: Deep inferior epigastric artery perforator (DIEP) flap surgery is one of the most common techniques for breast reconstruction using abdominal tissue. Although the DIEP flap reduces donor-site morbidity when compared with the conventional free transverse rectus abdominis musculocutaneous flap, violation of the anterior rectus sheath, rectus muscle, and motor nerves cannot be avoided. To further minimize tissue damage in the donor site, the use of a surgical robotic system for DIEP flap harvest with a totally extraperitoneal approach has been suggested. This totally extraperitoneal approach has a long learning curve because of the narrow preperitoneal space and the difficulty of converting a potential space to an actual space. Thus, the authors suggest a single-port robotic system optimized for narrow surgical spaces as a feasible option for DIEP flap harvest by a totally extraperitoneal approach, which has a shorter learning curve.

A 45-degree Upward Tension-Releasing Epicanthoplasty Performed in 712 Consecutive Cases.

BACKGROUND: Medial epicanthoplasty is commonly used to enhance the aesthetic outcomes of double-eyelid operations in Asia. However, epicanthoplasty can cause problems such as scarring and excessive exposure of the lacrimal lakes. OBJECTIVES: To resolve the problems associated with epicanthoplasty and to create more natural and long-lasting double-eyelid fold lines while minimizing incisions, we performed a 45-degree upward tension-releasing epicanthoplasty. MATERIALS AND METHODS: A total of 712 patients underwent 45-degree upward tension-releasing epicanthoplasty, with or without double eyelidplasty. A triangular skin flap was elevated at a 45-degree angle from the epicanthal fold. The surrounding area was dissected to eliminate the rigid connective tissue between the orbicularis muscle and the skin, which creates skin tension. The incisions were sutured, and a small incision toward the medial canthus was added to further decrease tension and create space for the triangular flap to be transposed. RESULTS: A total of 707 patients underwent 45-degree upward tension-releasing epicanthoplasty with the double-eyelid procedure, and 5 patients underwent 45-degree upward tension-releasing epicanthoplasty alone. No complications were observed for any patients, and 95% of patients were satisfied with this technique. CONCLUSIONS: The 45-degree upward tension-releasing epicanthoplasty can release the tension in the epicanthal fold, minimize scarring, and control lacrimal lake exposure. In particular, this method was effective for creating an in-out double-fold line starting from the epicanthus and for maintaining the double-eyelid line, which can reduce unnecessary incisional double-eyelid surgery.

Single-port robot-assisted prosthetic breast reconstruction with the da Vinci SP Surgical System: first clinical report.

Robot-assisted nipple-sparing mastectomy with immediate reconstruction is currently performed in an attempt to seek smaller and indistinct incisions. Robotic surgery system has been evolving under the concept of minimal invasive technique which is a recent trend in surgery. One of the latest version is the da Vinci SP Surgical System (Intuitive Surgical). In this report, we will share our experiences. Two patients underwent robot-assisted nipple-sparing mastectomy, each followed by immediate robot-assisted expander insertion and prepectoral direct-to-implant breast reconstruction, respectively. There was no open conversion or major postoperative complication. One patient experienced mild infection, which was resolved by intravenous antibiotic treatment. Simple docking process, multi-joint instruments, and third-arm functionality are among the new surgical system's advantages. The present cases suggest that robot-assisted nipple-sparing mastectomy with immediate reconstruction using the da Vinci SP Surgical System is feasible and safe. The promising features and potential application of da Vinci SP in breast reconstruction need further study.

Anterolateral thigh free flaps and radial forearm free flaps in head and neck reconstruction: A 20-year analysis from a single institution.

BACKGROUND: Reconstruction after removal of a malignant tumor in the head and neck region is crucial for restoring tissue integrity, function, and aesthetics. We retrospectively analyzed patients who underwent intraoral reconstruction surgery using radial forearm free flaps (RFFF) and anterolateral thigh free flaps (ALT) at a single institution to provide more information supporting the choice of a reconstruction method after removal of head and neck cancer. METHODS: The charts of 708 patients who underwent head and neck reconstruction between 1998 and 2018 at the Department of Plastic and Reconstructive Surgery at our institution were retrospectively reviewed. Patients' age, sex, and history of radiation therapy, diabetes mellitus, and smoking were retrieved. The primary cancer site, types of defects, and complications were investigated. RESULTS: Overall, 473 and 95 patients underwent reconstruction surgery with RFFF and ALT, respectively. RFFF was more often used in patients with cancers of the pharynx, larynx, esophagus, or tonsil, while ALT was more frequently used in patients with cancers of the mouth floor with tonsil or tongue involvement. The proportion of patients undergoing ALT increased gradually. Flap failure and donor site morbidities did not show significant differences between the two groups. CONCLUSIONS: RFFF and ALT flaps resulted in similar outcomes in terms of flap survival and donor site morbidity. ALT can be an option for head and neck reconstruction surgery in patients with large and complex defects or for young patients who want to hide their donor site scars.

Stromal vascular fraction injection to treat intractable radiation-induced rectovaginal fistula.

Rectovaginal fistula, which can arise after an injury to the vaginal canal or rectum, is a troublesome obstacle for patients' everyday life. In most cases, it can be covered with a local flap, but previous radiation therapy increases the recurrence rate, making it especially difficult to cure. As the application of stromal vascular fraction (SVF) obtained from enzymatically digested autologous adipose tissue has become increasingly common, several reports have advocated its effectiveness for the treatment of refractory wounds. In light of the angiogenic, regenerative characteristics of SVF, it was incorporated as a treatment option in two cases of rectovaginal fistula discussed here. As described in this report, irradiated rectovaginal fistulas in rectal cancer patients were successfully treated with SVF injection, and we suggest SVF as a feasible treatment option for cases of rectovaginal fistula that would otherwise be very difficult to cure.

Metformin Inhibits Transforming Growth Factor ß-Induced Fibrogenic Response of Human Dermal Fibroblasts and Suppresses Fibrosis in Keloid Spheroids.

ABSTRACT: Accumulation of excessive extracellular matrix (ECM) and aberrant transforming growth factor ß (TGF-ß) signaling pathway function can be potential therapeutic targets for keloid treatment. In this study, we examined the antifibrotic effect of metformin as a suppressor of TGF-ß signaling pathways in human dermal fibroblasts (HDFs) and keloid spheroids. Human dermal fibroblasts were stimulated with TGF-ß (10 ng/mL) and treated with metformin (10 mM). The mRNA and protein expression of ECM components were evaluated by quantitative polymerase chain reaction, western blot, and immunofluorescence assay. In addition, we immunohistochemically examined the expression levels of ECM proteins in keloid spheroids. After addition of metformin (10 mM), collagen types I and III and elastin mRNA levels were significantly decreased in HDFs, and collagen type I protein level was significantly decreased. In addition, the expression levels of collagen types I and III, fibronectin, and elastin were significantly reduced in keloid spheroids after treatment with metformin (100 mM). Collagen types I and III and p-Smad2/3 complex proteins were decreased in metformin-treated keloid spheroids. These findings indicated that metformin inhibits the expression of ECM components in TGF-ß-stimulated HDFs and keloid spheroids. Therefore, we suggest the potential of metformin as an effective agent for the treatment of keloids.

Hypofractionated Radiotherapy With Volumetric Modulated Arc Therapy Decreases Postoperative Complications in Prosthetic Breast Reconstructions: A Clinicopathologic Study.

BACKGROUND: Emerging radiation technologies are expected to provide a positive impact on the reduction in postoperative complications in patients receiving prosthetic breast reconstruction. This study aimed to determine whether hypofractionated radiation therapy(RT) with volumetric modulated arc therapy(VMAT) is superior to conventional RT in the setting of prosthetic reconstruction. METHODS: From retrospective data collections, postoperative complications were compared for all patients with mastectomy and staged prosthetic reconstruction without RT, with hypofractionation using 40 Gy in 15 fractions with VMAT (Hypo-VMAT) or conventional RT (50 Gy over 5 weeks). After harvesting subpectoral capsules from patients with informed consents, histologic analysis including immunohistochemistry and immunofluorescence for collagen type I, α-smooth muscle actin, CD34 and CD31 expression was performed. RESULTS: A total of 288 reconstructions without RT, 55 reconstructions with Hypo-VMAT, and 29 reconstructions with conventional RT were examined. During average follow-up period of 34.8 months, rates of overall complications were 6.3% in the no-radiation group, 18.2% in Hypo-VMAT group and 44.8% in conventional-RT group with significant differences (no-RT vs Hypo-VMAT: p=0.006; Hypo-VMAT vs conventional-RT: p=0.012). Levels of myofibroblasts and tissue fibrosis were lower in the Hypo-VMAT group than in conventional-RT group (p=0.016 and p=0.040, respectively), while those of progenitor cells and microvessel density were higher in the Hypo-VMAT group than in conventional-RT group (p<0.001 and p<0.001, respectively). CONCLUSION: We demonstrated that hypofractionated RT with VMAT served to reduce radiation-related morbidities in prosthetic reconstruction from a clinicopathologic perspective, compared to conventional RT. It may offer a practical strategy to mitigate radiation-related complications in clinical settings.

A Prospective Randomized Study: The Usefulness and Efficacy of Negative Pressure Wound Therapy with Lipidocolloid Polyester Mesh Compared to Traditional Negative Pressure Wound Therapy for Treatment of Pressure Ulcers.

To improve healing of pressure ulcer wounds, it is important to optimize the conditions of the area surrounding the wound. Negative pressure wound therapy (NPWT) promotes wound healing, however, the removal of NPWT can cause pain or focal bleeding, delaying wound healing or causing infection. In this study, we reviewed the efficacy of the lipidocolloid non-adherent dressing (Urgotul®) as a wound contact layer. A total of 38 patients from the same facility who applied NPWT from April 2016 to October 2019 were included and divided into two groups; NPWT with the lipidocolloid non-adherent dressing (group 1, experimental group, 19 patients) and NPWT only (group 2, control group, 19 patients). The condition of the wound was examined prior to NPWT application, at one week, and again at three weeks after application. No significant differences were found between groups for general characteristics, bacterial culture or photo analysis. However, when comparing groups based on the time of examination, there was a significant reduction of the wound size in group 1 (p = 0.001) but not in group 2 (p = 0.082). Therefore, the current study finds that using the lipidocolloid non-adherent dressing as a wound contact layer in NPWT stimulates healing by shrinking the size of the pressure ulcer wound.

Sex-related and racial variations in orbital floor anatomy.

BACKGROUND: Repair of the orbital floor following trauma or tumor removal remains a challenge because of its complex three-dimensional shape. The purpose of the present study is to understand normal orbital floor anatomy by investigating its differences across four groups (Caucasian American and East Asian, males and females) via facial bone computed tomography (CT). METHODS: A total of 48 orbits in 24 patients between 20 and 60 years of age were evaluated. Although most patients underwent CT scanning following trauma, the orbital walls were intact in all patients. Linear and angular measurements of the orbital floor were obtained from CT images. RESULTS: Orbital floor width, length, angle between the orbital floor and medial wall, and distance from the inferior orbital rim to the lowest point of the orbital floor did not show a statistically significant difference between groups. Angles made by the infraorbital rim, the lowest point of the floor, and the anterior border of the infraorbital fissure were statistically significantly wider in East Asian females than in male groups. The floor depth in East Asian females was significantly smaller compared to all the other groups. CONCLUSION: East Asian female population had smaller curvature and depth of an orbital floor than the other groups, which means racial and sex-related differences should be considered in the orbital floor reconstruction.

Inhibition of Wnt signaling pathway suppresses radiation-induced dermal fibrosis.

Progressive fibrosis of the dermal tissues is a challenging complication of radiotherapy whose underlying mechanism is not fully understood, and there are few available treatments. The canonical Wnt/ß-catenin signaling pathway plays an important role in fibrosis as well as in the epithelial-to-mesenchymal transition (EMT). We investigated whether inhibition of Wnt/ß-catenin signaling with sLRP6E1E2, a molecule that binds to extracellular Wnt ligands, ameliorated radiation-induced fibrosis both in vitro and in vivo. Radiation with a single dose of 2 Gy not only facilitated fibrosis in cultured human dermal fibroblasts via activation of the Wnt/ß-catenin pathway but also initiated EMT in cultured keratinocytes, developing collagen-producing mesenchymal cells. sLRP6E1E2-expressing adenovirus treatment exerted anti-fibrotic activity in irradiated cultured dermal fibroblasts and keratinocytes. In a mouse model, a single fraction of 15 Gy was delivered to the dorsal skins of 36 mice randomized into three groups: those receiving PBS, those receiving control adenovirus, and those receiving decoy Wnt receptor-expressing adenovirus (dE1-k35/sLRP6E1E2). The mice were observed for 16 weeks, and excessive deposition of type I collagen was suppressed by sLRP6E1E2-expressing adenovirus treatment. These results demonstrate that the modulation of the Wnt/ß-catenin pathway has the potential to decrease the severity of radiation-induced dermal fibrosis.