Search

Autologous fat grafting is among the safest and most effective treatments for soft-tissue restoration and augmentation, and many efforts have been made to improve its efficiency, including adipose-derived stem cell (ASC) supplementation. Here, we investigated the role of Notch ligand Delta-like ligand 4 (Dll4) in angiogenesis within grafted fat and its effect on graft retention, as well as the effect of Dll4 inhibition on ASC supplementation. Using a murine fat graft model, we investigated the expression of Dll4 in fat grafts and assessed the graft volume, vascularity, and perfusion within the graft, and ASC differentiation patterns depending on the blockade of Dll4. The underlying mechanism of Dll4 inhibition on ASC supplemented fat grafts was investigated using transcriptome analysis. Dll4 was highly expressed in vascular endothelial cells (ECs) within grafted fat, where Dll4-blocking antibody treatment-induced angiogenesis, promoting fat graft retention. In addition, its effect on fat graft retention was synergistically improved when ASCs were concomitantly supplemented. The expression of junctional proteins was increased in ECs, and inflammatory processes were downregulated in grafted fat upon ASC supplementation and Dll4 inhibition. Dll4 inhibition induced vascularization within the grafted fat, thereby promoting graft retention and exhibiting synergistic effects with concomitant ASC supplementation. This study serves as a basis for developing new potential therapeutic approaches targeting Dll4 to improve graft retention after cell-assisted transfer.

Immunomodulation is an essential consideration for cell replacement procedures. Unfortunately, lifelong exposure to nonspecific systemic immunosuppression results in immunodeficiency and has toxic effects on nonimmune cells. Here, we engineered hybrid spheroids of mesenchymal stem cells (MSCs) with rapamycin-releasing poly(lactic- co -glycolic acid) microparticles (RAP-MPs) to prevent immune rejection of islet xenografts in diabetic C57BL/6 mice. Hybrid spheroids were rapidly formed by incubating cell-particle mixture in methylcellulose solution while maintaining high cell viability. RAP-MPs were uniformly distributed in hybrid spheroids and sustainably released RAP for ~3 weeks. Locoregional transplantation of hybrid spheroids containing low doses of RAP-MPs (200- to 4000-ng RAP per recipient) significantly prolonged islet survival times and promoted the generation of regional regulatory T cells. Enhanced programmed death-ligand 1 expression by MSCs was found to be responsible for the immunomodulatory performance of hybrid spheroids. Our results suggest that these hybrid spheroids offer a promising platform for the efficient use of MSCs in the transplantation field.

Free muscle transfer for facial reanimation requires the sacrifice of motor nerves and muscles, which inevitably leads to donor site morbidity. To overcome this, the authors performed the interfascicular nerve splitting technique during neurovascular latissimus dorsi flap harvest. The aim of this study was to examine the efficacy of our interfascicular nerve splitting technique through the evaluation of donor site morbidity. Records of patients who underwent free latissimus dorsi flap using interfascicular nerve splitting technique between 2012 and 2016 were reviewed. Postoperative donor site morbidity was evaluated using electromyography, nerve conduction studies, and the Quick-Disabilities of Arm, Shoulder, and Hand questionnaire (QuickDASH). A total of 13 patients were analysed. Grades from electromyography and nerve conduction study were not significantly different between donor site and contralateral side (0.42±0.51 and 0.08±0.28, respectively, p = .073). QuickDASH scores showed different results over time. Preoperative QuickDASH scores averaged 1.57±2.34. At postoperative 6 months, the average QuickDASH score was 8.74±4.62, which was significantly different from the preoperative average (p = .001). At postoperative 12 months, QuickDASH scores averaged 2.62±3.19, which was an improvement from the postoperative 6-month score. However, it was not significantly different from the preoperative score (p = .059). The present study showed that interfascicular nerve splitting could minimize donor site morbidity. Also, our results suggest that the split nerve can function as a donor nerve. Our novel method could be a valuable option for minimizing donor site morbidity during facial reanimation surgery.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL)—a new category of anaplastic large cell lymphoma associated with textured breast implants—has a distinct variation in incidence and is especially rare in Asia. We report the first case of BIA-ALCL in Korea and present its histological and genetic characteristics. A 44-year-old female patient presented with a typical clinical course and symptoms, including breast augmentation with textured breast implants, late-onset peri-implant effusion, and CD30+ALK− histology, followed by bilateral implant removal and total capsulectomy. For histological analysis, we performed immunohistochemistry of the bilateral breast capsules. For transcriptome analysis, we identified highly upregulated gene sets employing RNA-sequencing and characterized the lymphoma immune cell components. In the lymphoma-associated capsule, CD30+ cells infiltrated not only the lymphoma lesion but also the peritumoral lesion. The morphologies of the myofibroblasts and vessels in the peritumoral lesion were similar to those in the tumoral lesion. We observed strong activation of the JAK/STAT3 pathway and expression of programmed death ligand-1 in the lymphoma. Unlike the molecular profiles of BIA-ALCL samples from Caucasian patients—all of which contained activated CD4+ T cells—the Asian patient’s profile was characterized by more abundant CD8+ T cells. This study contributes to a better understanding of the pathogenesis and molecular mechanisms of BIA-ALCL in Asian patients that will ultimately facilitate the development of clinical therapies. Level of Evidence: 5

Background The viable zone where adipocytes and/or adipose-derived stem cells survive is present at the surface of graft fat tissue; however, there is controversy regarding the zone thickness. Graft retention could be improved if more adipocytes are included in the zone. Objectives We hypothesize that a temporary reduction in adipocyte size prior to grafting could increase the number of adipocytes in the viable zone. We reduced the adipocyte size by treatment with MLN4924, which controls lipid accumulation in adipocytes, and investigated the histological and microenvironmental changes in grafted fat. Methods Subcutaneous fat harvested from wild-type C57BL/6J mice was chopped into small pieces; treated with dimethyl sulfoxide (control group), 0.25 μM MLN4924, or 0.5 μM MLN4924 for 4 days; and grafted into recipient C57BL/6J mice at the supraperiosteal plane of the skull. Results The reduced adipocyte size in response to MLN4924 treatment was restored within 8 weeks after fat grafting. The MLN4924-treated groups exhibited substantially greater graft volume, lower tissue hypoxia, and higher production of M2 macrophages compared with the control group. Conclusions Grafting with compact fat that had smaller adipocytes improved the microenvironment by modulating tissue hypoxia and macrophage polarization, leading to improved graft retention. Therefore, compact fat grafting may offer a new clinical strategy without the need for stem cell manipulation.

Objective: This study aimed to elucidate the role of the proangiogenic transcription factors Sox7 and Sox17 in the wound healing process and investigate the therapeutic potential of Dll4 blockade, which is an upstream regulator of Sox17, for the treatment of nonhealing wounds. Approach: After generating a full-thickness skin defect wound model of endothelial Sox7- and/or Sox17-deficient mice, we measured the wound healing rates and performed histological analysis. The effects of an anti-Dll4 antibody on wound angiogenesis in Sox7-deficient mice and db/db diabetic mice were assessed. Results: Sox7 and/or Sox17 deletion delayed wound healing. Moreover, the loss of Sox7 and Sox17 inhibited wound angiogenesis, without affecting the expression of the other. Of interest, after anti-Dll4 antibody treatment, Sox17 levels were increased and the suppression of angiogenesis was alleviated in Sox7-deficient mice and db/db diabetic mice. Consequently, Dll4 blockade effectively recovered the observed delay in wound healing. Innovation: The proangiogenic role of Sox7 and Sox17 in wound angiogenesis was addressed and effective treatment of nonhealing wounds by Dll4 blockade was suggested. Conclusion: This study revealed the proangiogenic role of the transcription factors Sox7 and Sox17 in wound angiogenesis. Furthermore, we suggest a novel method for treating nonhealing wounds by particularly targeting the Dll4-Sox17 axis.

Background Subdermal shaving is a surgical procedure for the treatment of axillary osmidrosis. In this procedure, a direct axillary incision is made, and the apocrine glands are removed. Insufficient subcutaneous tissue removal during subdermal shaving can lead to recurrence due to the presence of remaining apocrine glands, while excessive removal can injure the subdermal plexus and cause skin necrosis. We measured the depth of the apocrine glands from the basement membrane of the epidermis to develop a quantitative method of determining the thickness of the skin flap to be removed. Methods A chart review of patients who underwent subcutaneous shaving to treat osmidrosis between 2012 and 2019 was performed. Axillary subcutaneous tissues were harvested from five randomly chosen patients with osmidrosis before and after surgery. The apocrine gland depth was then measured via immunofluorescence (IF) staining of the collected tissues. A questionnaire was administered to 10 of the patients to investigate postoperative outcomes. Results Of the 47 total patients, six (12.8%) experienced recurrence, seven (14.9%) had complications, four (8.5%) had skin necrosis, two (4.3%) had hematomas, and one (2.1%) had an infection. One patient underwent reoperation due to hematoma. IF staining revealed the mean distance from the basal layer of the epidermis to the apocrine glands to be 1.4312±0.8064 mm. On the questionnaire, the mean patient rating of axillary odor was 8.6 pre-surgery and 4.4 post-surgery. Conclusions During subdermal shaving, the subcutaneous tissue must be preserved up to 14.312±8.064 mm from the epidermal basement membrane to remove the apocrine glands while preserving the subdermal plexus.

Lymphedema is a debilitating and progressive condition, which results in the accumulation of lymphatic fluid within the interstitial compartments of tissues and hypertrophy of adipose tissue due to the impairment of lymphatic circulation. The mainstay of current lymphedema treatment is nonsurgical management such as complex decongestive therapy and compression therapy. Recently, surgical treatment of lymphedema based on microsurgery has been developed to enable the functional recovery of lymphatic drainage and has complemented nonsurgical treatment. Lymphaticovenular anastomosis and vascularized lymph node transfer are representative physiologic surgeries in the treatment of lymphedema. Lymphaticovenular anastomosis is conducted to drain lymphatic fluid from obstructed lymphatic vessels to the venous circulation through surgically created lymphaticovenous shunts. Vascularized lymph node transfer involves harvesting lymph nodes with their vascular supply and transferring this vascularized tissue to the lymphedema lesion as a free flap. In addition to physiologic surgeries, ablative surgeries such as direct excision and liposuction also can be performed, especially for end-stage cases. Indications for surgical treatment vary across institutions. It is important not to delay physiologic surgery in mild to moderate cases of lymphedema.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a T-cell non-Hodgkin’s lymphoma that occurs in patients with at least one prior textured breast implant. BIA-ALCL has a relatively good prognosis when treated promptly. However, data on the methods and timing of the reconstruction process are lacking. Herein, we report the first case of BIA-ALCL in Republic of Korea in a patient who underwent breast reconstruction using implants and an acellular dermal matrix (ADM). A 47-year-old female patient was diagnosed with BIA-ALCL stage IIA (T4N0M0) and underwent bilateral breast augmentation using textured breast implants. She then underwent removal of both breast implants, total bilateral capsulectomy, adjuvant chemotherapy, and radiotherapy. There was no evidence of recurrence at 28 months postoperatively; therefore, the patient wished to undergo breast reconstruction surgery. A smooth surface implant was used to consider the patient’s desired breast volume and body mass index. The right breast was reconstructed with a smooth surface implant and an ADM in the prepectoral plane. Breast augmentation was performed on the left breast using a smooth surface implant. The patient was satisfied with the results and recovered fully with no complications.

While the transverse rectus abdominis myocutaneous (TRAM) flap is a popular option for abdominal-based breast reconstruction, abdominal wall morbidities such as bulging or hernia remain a concern. Here, we introduced a surgical technique for reinforcing the abdominal wall using an onlay autograft obtained from discarded zone IV tissue following a primary closure. We compared abdominal wall morbidities between patients receiving an onlay graft and those receiving primary closure only. We retrospectively reviewed the medical charts of patients who underwent breast reconstruction using a TRAM flap between December 2018 and May 2021. Additionally, we assessed donor-site morbidities based on physical examination. Of the 79 patients included, 38 had received a dermal graft and 41 had not. Donor-site morbidities occurred in 10 (24.5%) and 1 (2.6%) patients, and bulging occurred in 8 (19.5%) and 1 (2.6%) patients in the primary closure and dermal autograft groups, respectively. A statistically significant difference in the incidence of bulging was observed between the groups (p = 0.030). In conclusion, the introduction of a dermal autograft after primary closure can successfully ameliorate morbidities at the TRAM flap site.

Introduction:Chest wall osteoradionecrosis(ORN) in breast cancer is one of the most serious complications of radiation therapy. Treatment requires wide debridement and coverage with a well-vascularized flap. However, the extensive radiation-induced injury, and a limit to performing wide resection of the injured bones are challaged to treatment. Herein, we present our experience with chest wall ORN treated with contralateral breast Y-V flap.Case presentationAn 81-year-old woman diagnosed with ORN of the chest wall had a severe ptotic breast. Reconstruction was planned to cover the open wound of the chest wall using redundant contralateral breast tissue. The flap was elevated in the subfascial plane after an inverted-T incision was made in the lower pole and inframammary fold of the contralateral breast while preserving the perforators of the left lateral thoracic artery. The flap was spread in a Y-V advancement fashion to cover the open wound. The patient was discharged 2 weeks after surgery following suture removal. At 19 months post-operation, there were no complications or recurrences of ulcers. The patient was satisfied with the short recovery time and the surgical results.ConclusionThe contralateral breast Y-V flap allows simple and quick reconstruction, and having more options for chest wall reconstruction will allow for a more flexible treatment plan for each patient.

Nipple reconstruction methods include various techniques, such as the local flap technique, free nipple grafting, and filler injection. The local flap technique can provide less donor site morbidity than a free nipple graft, but leaves an additional scar near the nipple. We present a novel method for reconstruction of the nipple using a flap located on one side of the nipple. The flap has a teardrop shape consisting of a circle and two wings folded to one side. The two wings form a pillar and cap, and the de-epithelialized tip of one wing fills the internal dead space of the new nipple. We applied this nipple reconstruction technique in the case of a 61-year-old patient who had a vertical scar due to inverted-T reduction mammoplasty. The patient had lost her nipple in previous breast-conserving surgery. The immediate postoperative nipple projection was 10 mm. At the 7-month follow-up visit, the nipple projection was 7.5 mm. The teardrop flap is an innovative technique that leaves no additional scar by using the scar already present on one side of the nipple.

Background:Cell-assisted lipotransfer, a technique involving free fat grafting mixed with adipose-derived stromal cells, has gained popularity for enhancing fat graft retention. In terms of stem cell delivery, intravenous injection can be a novel alternative with clinical value. However, the effects

Background It remains unknown whether perfusion mapping using the SPY system can predict mastectomy skin flap necrosis in each type of breast surgery. We analyzed intraoperative indocyanine green (ICG) angiography images of breast cancer patients who underwent nipple-sparing mastectomy (NSM) with implant-based breast reconstruction, and evaluated the perfusion of the nipple-areolar complex (NAC) with the SPY Elite system to predict NAC necrosis with a single quantitative value. Methods We analyzed nipple perfusion in 30 patients from October 2016 to November 2018. After NSM, ICG injection and SPY angiography were performed to characterize NAC perfusion before immediate reconstruction. The nipple perfusion rate was measured by analyzing fluorescence at the central point of the nipple, and the presence of NAC necrosis was evaluated at 5 days and 1 month postoperatively. Results Three of the 30 patients developed NAC necrosis that secondarily healed within 1 month, and five developed NAC necrosis and underwent surgical debridement within 1 month. Seven of eight patients with a perfusion rate

Rationale: Central nervous system has low vascular permeability by organizing tight junction (TJ) and limiting endothelial transcytosis. While TJ has long been considered to be responsible for vascular barrier in central nervous system, suppressed transcytosis in endothelial cells is now emerging as a complementary mechanism. Whether transcytosis regulation is independent of TJ and its dysregulation dominantly causes diseases associated with edema remain elusive. Dll4 signaling is important for various vascular contexts, but its role in the maintenance of vascular barrier in central nervous system remains unknown. Objective: To find a TJ-independent regulatory mechanism selective for transcytosis and identify its dysregulation as a cause of pathological leakage. Methods and Results: We studied transcytosis in the adult mouse retina with low vascular permeability and employed a hypertension-induced retinal edema model for its pathological implication. Both antibody-based and genetic inactivation of Dll4 or Notch1 induce hyperpermeability by increasing transcytosis without junctional destabilization in arterial endothelial cells, leading to nonhemorrhagic leakage predominantly in the superficial retinal layer. Endothelial Sox17 deletion represses Dll4 in retinal arteries, phenocopying Dll4 blocking-driven vascular leakage. Ang II (angiotensin II)–induced hypertension represses arterial Sox17 and Dll4, followed by transcytosis-driven retinal edema, which is rescued by a gain of Notch activity. Transcriptomic profiling of retinal endothelial cells suggests that Dll4 blocking activates SREBP1 (sterol regulatory element-binding protein 1)-mediated lipogenic transcription and enriches gene sets favorable for caveolae formation. Profiling also predicts the activation of VEGF (vascular endothelial growth factor) signaling by Dll4 blockade. Inhibition of SREBP1 or VEGF-VEGFR2 (VEGF receptor 2) signaling attenuates both Dll4 blockade–driven and hypertension-induced retinal leakage. Conclusions: In the retina, Sox17-Dll4-SREBP1 signaling axis controls transcytosis independently of TJ in superficial arteries among heterogeneous regulations for the whole vessels. Uncontrolled transcytosis via dysregulated Dll4 underlies pathological leakage in hypertensive retina and could be a therapeutic target for treating hypertension-associated retinal edema.

Rotation-advancement repair (RAR) has been the most widely used technique for unilateral cleft lip repair. We recently used a straight-line repair with medial orbicularis muscle lengthening (SLR-ml) technique, based on the hypothesis that it could minimize the postoperative scar appearance without causing s short-lip deformity when muscle reorientation is performed correctly. A retrospective cohort study was conducted on unilateral complete cleft lip patients who underwent cheiloplasty between 2009 and 2017. Two cheiloplasty techniques were compared: RAR and SLR-ml. Outcomes were evaluated by assessing follow-up photographs using three methods: (1) glance impression on a five-point scale, (2) Manchester Scar Scale, and (3) indirect anthropometry. Seventy-one patients were analysed: 41 in the RAR group (28 male, 13 female) and 30 in the SLR-ml group (15 male, 15 female). The glance impression (P=0.506) and Manchester Scar Scale (P=0.347) scores did not differ between the groups. According to the symmetry ratio (cleft side value/non-cleft side value), vertical lip height (P=0.804), horizontal lip length (P=0.881), and Cupid's bow width (P=0.122) did not differ significantly between the groups. The preoperative lip height discrepancy was not correlated with the postoperative vertical lip height. The SLR-ml method can be regarded as a successful tool for symmetric repair of unilateral cleft lip.

Background The big data provided by Health Insurance Review and Assessment (HIRA) contains data from nearly all Korean populations enrolled in the National Health Insurance Service. We aimed to identify the incidence of facial fractures and its trends in Korea using this big data from HIRA. Methods We used the Korean Standard Classification of Disease and Cause of Death 6, 7 for diagnosis codes. A total of 582,318 patients were included in the final analysis. All statistical analyses were performed using SAS software and SPSS software. Results The incidence of facial fractures consistently declined, from 107,695 cases in 2011 to 87,306 cases in 2016. The incidence of facial fractures was the highest in June 2011 (n = 26,423) and lowest in January 2014 (n = 10,282). Nasal bone fractures were the most common, followed by orbit and frontal sinus fractures. The percentage of nasal bone fractures declined, whereas those of orbital fractures increased from 2011 to 2016 (P < 0.001). Among orbital fractures, inferior wall fractures were the most common, followed by medial wall fractures. Among mandibular fractures, angle fractures were the most common, followed by condylar process and symphysis fractures. Although it was difficult to predict the most common type of zygomatic and maxilla fractures, their incidence consistently declined since 2011. Conclusion We observed trends in facial fractures in Korea using big data including information for nearly all nations in Korea. Therefore, it is possible to predict the incidence of facial fractures. This study is meaningful in that it is the first study that investigated the incidence of facial fractures by specific type., Graphical Abstract

Background: Acellular dermal matrix (ADM) in implant-based breast reconstruction can show various ultrasound (US) findings. However, there are limited reports on the US features of the ADM. The aims of this study were to evaluate US findings of the ADM in implant-based breast reconstruction and correlate them with histopathological findings. Methods: Between January 2015 and August 2020, 250 women who underwent implant-based breast reconstruction with ADM and a breast US examination at 6 months to 1 year after reconstruction were retrospectively analyzed. Abnormal US findings were classified as type 1 (focal thickening with decreased echogenicity), 2 (diffusely hyperechoic), or 3 (bright echogenic spots). ADM biopsy was performed in 33 patients who underwent second stage or revisional surgeries. Results: In total, 176 consecutive women with 207 US findings were analyzed. The US findings were normal in 52.2% of the women. The percentages of type 1, 2, and 3 patients were 13.5%, 11.1%, and 23. 2%, respectively. These patients had microscopic findings that showed patchy areas with chronic inflammatory infiltrates, dense collagen bundles without degenerative or inflammatory changes, and empty spaces or degenerated foci unaccompanied by inflammation. Conclusion: Knowing the various ADM presentations on US can help avoid unnecessary invasive procedures.

Background Monitoring free muscle flaps with skin grafts is difficult. To intensify the monitoring process for this type of flap, a small skin paddle was included in the flap and analyzed its effects. Methods A retrospective analysis of all patients who underwent scalp reconstruction with a free latissimus dorsi flap and skin graft between 1994 and 2016 was conducted. Flap monitoring was proceeded using a combination of clinical examination and handheld Doppler for both types of flaps. Results A total of 71 patients were included in this study and were divided into a study group (skin paddle included; n = 30) and a control group (conventional method; n = 41). The time between initial surgery to pedicle exploration was significantly shorter in the study group (11.3 ± 2.5 vs 79.8 ± 42.6 hours; P = .024). The flap salvage rate was significantly higher in the study group (100% vs 16.7%; P = .048). Conclusion The efficacy of flap monitoring and flap salvage outcomes were improved by including a small monitoring skin flap.

Rationale: Vascular endothelial growth factor (VEGF) signaling is a key pathway for angiogenesis and requires highly coordinated regulation. Although the Notch pathway-mediated suppression of excessive VEGF activity via negative feedback is well known, the positive feedback control for augmenting VEGF signaling remains poorly understood. Transcription factor Sox17 is indispensable for angiogenesis, but its association with VEGF signaling is largely unknown. The contribution of other Sox members to angiogenesis also remains to be determined. Objective: To reveal the genetic interaction of Sox7, another Sox member, with Sox17 in developmental angiogenesis and their functional relationship with VEGF signaling. Methods and Results: Sox7 is expressed specifically in endothelial cells and its global and endothelial-specific deletion resulted in embryonic lethality with severely impaired angiogenesis in mice, substantially overlapping with Sox17 in both expression and function. Interestingly, compound heterozygosity for Sox7 and Sox17 phenocopied vascular defects of Sox7 or Sox17 homozygous knockout, indicating that the genetic cooperation of Sox7 and Sox17 is sensitive to their combined gene dosage. VEGF signaling upregulated both Sox7 and Sox17 expression in angiogenesis via mTOR pathway. Furthermore, Sox7 and Sox17 promoted VEGFR2 (VEGF receptor 2) expression in angiogenic vessels, suggesting a positive feedback loop between VEGF signaling and SoxF. Conclusions: Our findings demonstrate that SoxF transcription factors are indispensable players in developmental angiogenesis by acting as positive feedback regulators of VEGF signaling.

BACKGROUNDS Cross-face nerve grafting (CFNG) is an important treatment for patients with facial palsy. Currently, two-stage CFNG is frequently performed. CFNG is performed first, followed by coaptation when innervation reaches the grafted nerve ending. The present study compared single-stage CFNG with conventional two-stage CFNG. METHODS We retrospectively reviewed data of 17 patients who underwent CFNG with zygomatic and buccal branch with hypoglossal crossover. Patients with single-stage (group 1) and two-stage (group 2) CFNG were comparatively analyzed 2 years postoperatively. There were nine and eight patients in groups 1 and 2, respectively. The patient's perioperative status was measured with imaging and animation using the Yanagihara grade, altitude, and angle differences of the oral commissure and eye closure. RESULTS Patients in group 1 could recognize their first postoperative spontaneous movement earlier than those in group 2 (268.3 ± 25.1 days vs. 327.5 ± 51.3 days, respectively, p = 0.015). The Yanagihara grade significantly improved for patients in both groups postoperatively (group 1: 12.8 ± 5.5 to 25.3 ± 6.1, p

Capsular contracture is one of the most common complications of expander–implant breast reconstruction. Recently, clinical reports have shown that use of an acellular dermal matrix (ADM) to cover breast implants decreases incidence of capsular contracture, but the underlying mechanism is unclear. Here, we examine how ADM reduces capsular formation in expander–implant breast reconstruction and identify cellular and molecular mechanisms of ADM-mediated reduction of capsular contracture in nonirradiated and irradiated patients. Thirty patients who underwent immediate two-stage implant-based breast reconstruction were included; 15 received radiotherapy. While the tissue expander was changed to permanent silicone implant, biopsies of the subpectoral capsule and ADM capsule were performed. Capsule thickness, immunohistochemistry of α-smooth muscle actin (αSMA), vimentin, CD31, F4/80 expression, αSMA and CD31 coexpression, and relative gene expression levels of transforming growth factor (TGF)-β1 and platelet-derived growth factor (PDGF)-B were investigated. Irradiated submuscular capsules were thicker than nonirradiated submuscular capsules, but the thickness of ADM capsules did not significantly differ between nonirradiated and irradiated groups. Levels of myofibroblasts, fibroblasts, vascularity, EndoMT, and macrophages were significantly lower in ADM capsules than in submuscular capsules. With the exception of EndoMT, all others were increased in irradiated submuscular capsules compared with nonirradiated submuscular capsule, while none significantly differed between nonirradiated and irradiated ADM capsules. Use of ADM reduced myofibroblasts, vascularity, fibroblasts, and EndoMT in capsule tissues. Moreover, ADM use decreased macrophages, a key regulator of tissue fibrosis, as well as TGF-β1 and PDGF-B expression. We hope that these results provide basic concepts important for prevention of capsular contracture.

Background— Intracranial aneurysm (IA) is a common vascular disorder that frequently leads to fatal vascular rupture. Although various acquired risk factors associated with IA have been identified, the hereditary basis of IA remains poorly understood. As a result, genetically modified animals accurately modeling IA and related pathogenesis have been lacking, and subsequent drug development has been delayed. Methods and Results— The transcription factor Sox17 is robustly expressed in endothelial cells of normal intracerebral arteries. The combination of Sox17 deficiency and angiotensin II infusion in mice induces vascular abnormalities closely resembling the cardinal features of IA such as luminal dilation, wall thinning, tortuosity, and subarachnoid hemorrhages. This combination impairs junctional assembly, cell-matrix adhesion, regeneration capacity, and paracrine secretion in endothelial cells of intracerebral arteries, highlighting key endothelial dysfunctions that lead to IA pathogenesis. Moreover, human IA samples showed reduced Sox17 expression and impaired endothelial integrity, further strengthening the applicability of this animal model to clinical settings. Conclusions— Our findings demonstrate that Sox17 deficiency in mouse can induce IA under hypertensive conditions, suggesting Sox17 deficiency as a potential genetic factor for IA formation. The Sox17 -deficient mouse model provides a novel platform to develop therapeutics for incurable IA.

Antiangiogenic therapy has a clinical benefit in only a subpopulation of high-grade glioma (HGG) patients. Kim et al. show that in an orthotopic HGG model, high levels of Sox7 in tumor vessels correlate with improved survival by anti-VEGFR2 antibody, suggesting a potential mechanism of heterogeneous therapeutic outcome to antiangiogenic therapy., High-grade glioma (HGG) is highly angiogenic, but antiangiogenic therapy has transient clinical benefit in only a fraction of patients. Vascular regulators of these heterogeneous responses remain undetermined. We found up-regulation of Sox7 and down-regulation of Sox17 in tumor endothelial cells (tECs) in mouse HGG. Sox7 deletion suppressed VEGFR2 expression, vascular abnormality, hypoxia-driven invasion, regulatory T cell infiltration, and tumor growth. Conversely, Sox17 deletion exacerbated these phenotypes by up-regulating Sox7 in tECs. Anti-VEGFR2 antibody treatment delayed tumor growth by normalizing Sox17-deficient abnormal vessels with high Sox7 levels but promoted it by regressing Sox7-deficient vessels, recapitulating variable therapeutic responses to antiangiogenic therapy in HGG patients. Our findings establish that Sox7 promotes tumor growth via vessel abnormalization, and its level determines the therapeutic outcome of VEGFR2 inhibition in HGG. In 189 HGG patients, Sox7 expression was heterogeneous in tumor vessels, and high Sox7 levels correlated with poor survival, early recurrence, and impaired vascular function, emphasizing the clinical relevance of Sox7 in HGG.

A destabilized tumor vasculature leads to limited drug delivery, hypoxia, detrimental tumor microenvironment, and even metastasis. We performed a side-by-side comparison of ABTAA (Ang2-Binding and Tie2-Activating Antibody) and ABA (Ang2-Blocking Antibody) in mice with orthotopically implanted glioma, with subcutaneously implanted Lewis lung carcinoma, and with spontaneous mammary cancer. We found that Tie2 activation induced tumor vascular normalization, leading to enhanced blood perfusion and chemotherapeutic drug delivery, markedly lessened lactate acidosis, and reduced tumor growth and metastasis. Moreover, ABTAA favorably altered the immune cell profile within tumors. Together, our findings establish that simultaneous Tie2 activation and Ang2 inhibition form a powerful therapeutic strategy to elicit a favorable tumor microenvironment and enhanced delivery of a chemotherapeutic agent into tumors.

Background Repairing orbital wall fractures can result in serious complications, including enophthalmos, diplopia, or even blindness. Especially, surgeons worry about damaging the optic nerve while dissecting the optic canal area. We avoid these complications by using a navigation system that was adapted to stereotactic concept based on three-dimensional imaging of the patient's anatomy. Here, we report 5 cases of orbital wall fracture that were repaired using a navigation system. Methods The Navigation System II (Stryker, Freiburg, Germany) and the iNtellect Cranial Navigation (version 1.1) platform were used for each operation. A computer-assisted navigation surgery was performed according to the following procedures: (1) image set, (2) planning, (3) apparatus setup, (4) registration, and (5) intraoperative navigation. Operations were performed under general anesthesia. Dissection was performed up to the periosteum immediately anterior to the optic canal, near the fracture. Vulnerable surrounding structures were identified with the intraoperative pointer. After navigation, we inserted an implant into the defect, successfully, avoiding damage to the optic canal and optic nerve. Results None of the patients had any surgical complications. Postoperative computed tomography scans demonstrated that the fractures were corrected, and continuity was maintained without displacement. The three-dimensional image allowed us to easily visualize intraoperative anatomical structure, allowing us to avoid unnecessary procedures and to correct the orbital wall. The mean volume of fractured orbital cavity was 29.2 cm(3) (range, 28.3-30.4 cm(3)) preoperatively and 27.0 cm(3) (range, 25.9-28.5 cm(3)) postoperatively; thus, the defects were corrected by 2.2 cm(3) (range, 1.3-2.8 cm(3)) on average. Conclusions We used a navigation system to perform accurate and safe surgery in patients with extensive orbital wall fracture, including around the optic canal. By using the functions to visualize the locations indicated by the pointer, we were able to perform successful dissections and implantations in areas adjacent to the optic canal. The good outcomes obtained here provide evidence that surgical correction of the orbital wall using a navigation system is useful in cases of deep, extensive orbital wall fracture.

To improve the biocompatibility and mechanical strength of porous hydroxyapatite (HA) scaffolds that have high osteoconduction, we coated them with 1, 5, or 10 wt% poly(L-lactic acid) (PLLA). In the 5 and 10 wt% PLLA-coated groups, osteoblast proliferation rates were higher than those in non-coated and 1 wt% PLLA-coated groups. The alkaline phosphatase (ALP) activity was highest in the 5 wt% PLLA-coated group. In addition, the porosity was highest in the non-coated HA group (82 %), whereas it was 72, and 41 % in the 5, and 10 wt% PLLA-coated groups, respectively. Scaffold strength increased in proportion to the concentration of PLLA coating. Overall, the 5 wt% PLLA scaffold had best characteristics when considering osteoblast proliferation, ALP activity, porosity, and compressive strength. We next tested this scaffold in an in vivo alveolar defect rabbit model. Multi-detector row computed tomography showed that non-coated and 5 wt% PLLA-coated HA groups had a similar high density. Adequate osteogenesis was observed by histological analysis in the non-coated HA and 5 wt% PLLA-coated HA groups. In addition, sufficient mineralization was observed in the coated scaffolds by X-ray fluorescence spectroscopy without significant adverse effects. Therefore, based on our findings, a PLLA-coated porous HA scaffold may be a suitable bone substitute for the correction of bone defects.

Hydroxyapatite (HA) is a well-known biocompatible bone substitute. Porous HA is more resorbable and osteoconductive compared with non-porous HA, and has been studied both experimentally and clinically. However, the mechanical strength of porous HA scaffolds is known to be weak. In this study, we developed a porous HA scaffold coated with a synthetic biodegradable polymer, poly(l-lactic acid) (PLLA), to strengthen the scaffold. PLLA-coated HA pellets were used to investigate the in vitro proliferation and alkaline phosphatase (ALP) activity of osteoblasts. PLLA-coated porous HA scaffolds were observed using scanning electron microscopy to investigate surface characteristics, porosity, and mechanical strength. PLLA coating concentration varied from 2 to 10 wt%. Osteoblast proliferation was higher in HA samples coated with PLLA compared with non-coated. ALP activity was highest on 8 wt% PLLA-coating after 3 days and on 4 wt% and 6 wt% PLLA after 9 and 12 days. Porous HA scaffolds with higher concentrations of PLLA were found to have a smoother, flatter surface. This enhanced proliferation and attachment of osteoblasts onto the porous HA scaffold. PLLA solution at a concentration of 10 wt% decreased scaffold porosity to half that of HA scaffolds with no PLLA coating. Scaffold mechanical strength was increased two-fold with a PLLA concentration of 2 wt%. Based on in vitro experimentation, it can be concluded that PLLA-coating on porous HA scaffolds enhances both the biocompatibility and the mechanical strength.

Gynecomastia is a benign, excessive development of the male breast that occurs at an overall incidence of 32–36 %. The authors effectively removed peripheral fat tissues with power-assisted liposuction (PAL) and periareolar glandular tissues with a cartilage shaver in a series of patients. The small periareolar incisions were not easily recognized. Between February 2010 and April 2012, the charts of 15 patients (28 breasts) treated with PAL and a cartilage shaver were retrospectively reviewed. The mean volume of fat tissue removed with liposuction was 319 mL, and the mean volume of glandular tissue removed with the cartilage shaver was 70 mL. The mean follow-up period was 11.2 months. No infection, nipple–areola complex necrosis, nipple retraction, or saucer deformity was encountered in this series. Intraoperative bleeding occurred in one patient. Mild asymmetries developed in three patients. Use of PAL and a cartilage shaver for the treatment of gynecomastia allows for effective removal of both the fat and the glandular tissue of the breast through a minimal periareolar incision. This technique can achieve excellent aesthetic results with inconspicuous scarring. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

In this report, the authors present the experience on the reconstruction of the totally degloved foot and extremely long soft tissue defect of a lower limb with the combined free tissue transfer using the anterolateral thigh flap as a link in two male patients between October 2009 and December 2010. The anterolateral thigh flap has been commonly used as a link between the recipient site and the distal flap. The anterolateral thigh flap and latissimus dorsi muscle flap were selected for the distal flap, according to their reconstructive needs. Two combined free flaps survived without major complication. The authors could salvage of the lower extremity through the reconstruction of complex wound with the combined free tissue transfer using the anterolateral thigh flap as a link. This combined flap may be an alternative for reconstruction of complex soft tissue defect in the lower extremity. © 2012 Wiley Periodicals, Inc. Microsurgery, 2012.

Poly(l-lactic acid) (PLLA) is a synthetic polyester that has been widely used in medicine. However, the degradation of PLLA can be accompanied by an inflammatory reaction, and it is difficult to control the duration of the degradation of PLLA. Thus, a sustained NSAID release porous structured PLLA was fabricated by using a solvent dispersion method. This novel drug release system would provide a consistent release of NSAIDs at a desirable concentration. PLLA and NSAIDs (Sulindac) were dissolved in methylene chloride. After they had homogenously dispersed, the solvent was isolated. Non-porous and porous PLLA substrates mixed with various concentrations (1, 5, and 9 %) of Sulindac were prepared. A morphological examination with a scanning electron microscope was performed. The elution experiment of Sulindac was implemented for 5 days. The drug release and the degradation of the compound in simulated body fluids were examined. No Sulindac particles were identified on the surface of the non-porous compound, however, they were found on that of the porous one. No porosity was found in the cross-section of the non-porous compound. During a 5 day period, the amount of the release of Sulindac was 3.9–17.6 mg/L in the non-porous compound and 21.5–35.1 mg/L in the porous one. In the non-porous compound, the amount of Sulindac released was found to be 3–5 ppm for 20–150 days. In the porous compound, it was found to be 137.7 ppm for 10 days initially. As time elapsed, however, there was a tendency of the release rate to gradually decrease. The authors attempted to prepare a sustained drug release system, which can maintain the concentration of drugs during a longer period in an in vivo setting. This compound could be applied in various ways in the field of material engineering.

Recently, the reverse-flow (distally based) anterolateral thigh flap has been used for soft tissue reconstruction around the knee [1-5], and it has several advantages such as a long pedicle, a sufficient amount of tissue, possible composite transfer with fascia lata and minimal donor site morbidity [1]. However, this flap has a risk of venous congestion from the reverse blood flow and resistance of the venous valves [2-4]. This might cause the development of flap failure. In the cases of flap-threatening venous congestion after the reconstruction of an oncologic defect of the knee with reverse-flow anterolateral thigh island flap, the authors performed venous supercharge using the greater saphenous vein with a reliable vessel diameter and salvaged the flap successfully. We present the clinical considerations in the salvage of a venous congested reverse-flow anterolateral thigh flap and the clinical course of this flap with a literature review. A 54-year-old male patient presented with a mass of 7×6 cm on the left knee. Biopsy of the lesion revealed a myxofibrosarcoma. The distant metastasis was not detected in preoperative evaluation. After wide excision of the malignancy, a soft tissue defect with a dimension of 8×8 cm over the left knee was noted (Fig. 1). We planned for the reconstruction the composite defect using a distally based anterolateral thigh island flap. Fig. 1 After wide excision of the myxofibrosarcoma, a soft tissue defect with a dimension of 8×8 cm over the left knee was noted. The perforators were detected with a hand held Doppler probe preoperatively. The anterolateral thigh island flap including a musculocutaneous perforator was elevated and the descending branch of the lateral circumflex femoral vessel was dissected distally. The descending branch contained two venae comitantes. Two valve areas were observed at the pedicle between the flap and the descending branch. We clamped the pedicle proximally to assess the retrograde flow into the flap. After observation for the flap circulation, the pedicle was ligated proximally. Venous engorgement was detected at the area proximal to the venous valve before the flap insetting. The pedicle measured 16 cm in length, with the pivot point located 7 cm above the patella. A split-thickness skin graft was performed to the closure of the donor-site without any tension. The refilling of the flap was relatively rapid immediately postoperatively; however, the venous congestion was not significant. Venous congestion of the flap developed slowly postoperatively at 10 hours, and worsened at 15 hours, threatening the survival of the flap; a reoperation was thus performed. A thrombus had formed at the proximal site of the venous valve and obstructed the venous drainage. After opening the ligated proximal venous end, we removed the thrombus and planned venous supercharge. The greater saphenous vein was detected at the medial side of the knee, and dissected 30 cm in length to reach the proximal venous end of the descending branch of the lateral circumflex femoral vessel. The venous supercharge was performed through the anastomosis of the greater saphenous vein and the vena comitans of the descending branch of the lateral circumflex femoral artery (Fig. 2). The diameter of the greater saphenous vein was 2 mm. After the venous supercharge, the congestion of the flap was improved and the flap survived. Partial necrosis developed in the distal part of the flap. The necrotic tissue was debrided and covered with minor wound revision (Fig. 3). Fig. 2 The scheme of the venous supercharge of the distally based anterolateral thigh island flap using the greater saphenous vein. DB, the descending branch of the lateral circumflex femoral vessel; P, the perforator to the anterolateral thigh island flap; ... Fig. 3 Appearance of the flap 2 months after the operation. Through a review of the literature of cases of reverse-flow anterolateral thigh flap (Appendix), we find that the flap has a noticeable clinical course (Fig. 4). If the perforators do not arise from the descending branch of the lateral circumflex femoral artery, the flap should be raised as a free flap or a bifurcation of the transverse and descending branch of lateral circumflex femoral vessel should be included or a bypass vein graft used [1,2]. Fig. 4 The clinical course of reverse-flow anterolateral thigh flap. ALT, anterolateral thigh; LCFA, lateral circumflex femoral artery. In a large number of cases, this flap had no complications [1,5]. Two cases of necrosis of partial flap among 17 cases were reported by Demirseren et al. [5], while no vascular complications in 3 cases were noted by Pan et al. [1] who claimed that the flap is safe and reliable. However, the reverse-flow anterolateral thigh flap has a risk of venous congestion because of the reverse blood flow and resistance of the venous valves [2,3]. The authors believe that the kinking and tension of the pedicle after the flap insetting were also possible causes of venous congestion. Some previous reported cases of venous congestion have been resolved with conservative treatment, but we experienced flap-threatening venous congestion, salvaged by venous supercharge using the greater saphenous vein. It is crucial to make a proper decision when venous congestion develops during or after a reverse-flow anterolateral flap operation. If the venous congestion occurs directly after the temporary clamping of the proximal portion of the pedicle, some alternatives which can save the flap are available, such as venous augmentation [3,4], vein graft for bypass [2], or free flap [1]. However, if the venous congestion occurs insidiously, as in this case, there is a need for close monitoring of the flap. Furthermore, if the venous congestion is severe enough to threaten the survival of the flap, reoperation needs to be performed. We believe that the venous engorgement between the venous valve and the flap is an indicator of the potential need for supercharge in the reverse-flow anterolateral thigh flap of slowly developed venous congestion according to our clinical experience. The reverse-flow anterolateral thigh flap could be worthwhile method in the soft tissue reconstruction around the knee through a consideration of the clinical course and preparation for venous congestion and salvage operation.

In this report, the authors present the experience on the reconstruction of the totally degloved foot and extremely long soft tissue defect of a lower limb with the combined free tissue transfer using the anterolateral thigh flap as a link in two male patients between October 2009 and December 2010. The anterolateral thigh flap has been commonly used as a link between the recipient site and the distal flap. The anterolateral thigh flap and latissimus dorsi muscle flap were selected for the distal flap, according to their reconstructive needs. Two combined free flaps survived without major complication. The authors could salvage of the lower extremity through the reconstruction of complex wound with the combined free tissue transfer using the anterolateral thigh flap as a link. This combined flap may be an alternative for reconstruction of complex soft tissue defect in the lower extremity.

Approximately half of the patients who have neurofibroma also develop vascular deformities and vascular malformations inside the neurofibroma masses [1]. Therefore, there is a high-risk of hemorrhage during surgery. Many methods have been reported for reducing hemorrhage such as hypotensive anesthesia [2], preoperative arterial embolization [3], and vasa vasorum ligation [1]; however, the effectiveness of these methods is questionable. If the neurofibroma mass is localized, the continuous loop-shaped suture ligation procedure [4] will help reduce the bleeding. We report our experience with reducing hemorrhage by comparing several surgical methods for hemostasis in extensive giant neurofibromas. A 69-year-old female patient presented with extensive giant neurofibromas throughout her body and massive neurofibromas on her buttocks and thighs, along with aggravating lower back pain, difficulty in walking, and mood disorder. The dimensions of the mass were 50×50×16 cm and it covered most of the patient's lower extremities (Fig. 1). The patient's weight was 67 kg. A preoperative pelvic magnetic resonance imaging was performed and there was no sign of malignancy, hematoma, or necrosis. There was neither skin ulcer nor skin necrosis. Fig. 1 Giant neurofibroma on the abdomen, both buttocks, and thighs in a 69-year-old woman. Note the 50×50×16 cm sized mass. Anterior and posterior view. During the first operation, we used Bovie electrocautery (ValleyLab, Boulder, CO, USA), bipolar cautery, and hemoclips. However, we stopped the surgery because of massive intraoperative bleeding. The patient received 15 units of packed red blood cells and 5 units of fresh frozen plasma during the transfusion. Subsequently, the authors planned a second-stage operation. During the first operation we resected 10 kg of weighed mass during a 9 hours and 40 minutes operation. During the second operation we controlled hemorrhage using hemostatic forceps and manual ligature. The total mass resected during the second operation was 13 kg. The patient received 5 units of packed red blood cells intraoperatively and 3 units postoperatively. The second operation time was 9 hours and 15 minutes. Compressive dressings were maintained after the surgery. The patient's vital signs were hemodynamically stable and there were no complications, such as lymphedema or bleeding; however, wound healing was delayed. A negative pressure wound therapy was helpful for promoting wound healing. Four months after the two operations, the wound was well healed, and the shape of the buttocks and thighs were anatomically appropriate (Fig. 2). The patient's lower back pain also improved and she regained a normal gait. Fig. 2 Postoperative result 4 months after the second operation. Right lateral and posterior view. The authors resected almost the same quantity of tumor mass during each operation from the patient; however, the amount of bleeding during the second operation was much less than that during the first operation. Therefore, we believe that a tedious process of hemostasis using hemostatic forceps and manual ligature was more effective than electrocautery for reducing hemorrhage during surgery.