Efficacy of Immediate Postoperative Single Fractional 10 Gy Radiotherapy for Earlobe Keloids.

BACKGROUND: The ear is a common site for keloid formation, typically due to ear piercing or trauma. Auricular keloids are always difficult to treat and pose a challenging situation. The purpose of this study is to present our experience treating earlobe keloids through complete surgical excision followed by immediate postoperative single fraction 10 Gy radiation therapy either on the same day or the next day. METHODS: The authors retrospectively evaluated 48 patients with 71 earlobe keloids treated with complete surgical excision followed by single-fractional 10 Gy radiotherapy within 24 hours from May 2021 to December 2022. The outcome was reported with a recurrence-free rate and side effects. RESULTS: The mean follow-up period was 20.8 months. All patients tolerated the treatments well. The overall recurrence-free rate was 100%. There were only 2 grade III radiation dermatitis. There were no reports of second malignancies or severe complications. CONCLUSIONS: The authors have obtained excellent outcomes from treating earlobe keloids through complete excision followed by postoperative radiotherapy with a single fractional dose of 10 Gy on the same day or the next day.

Aesthetic reconstruction of retroauricular keloid: Creating a keystone flap from the mastoid-helix area.

Advances in aesthetic rhinoplasty using conchal cartilage grafts have led to a high occurrence of retroauricular keloids. The purpose of this study is to introduce our surgical experiences using a keystone flap in retroauricular keloids following conchal cartilage grafts. The present study is a retrospective review of patients with pathologically confirmed retroauricular keloids following conchal cartilage grafts. These cases were surgically excised and we covered the defect with a keystone flap followed by one-time steroid injection at postoperative day 14 and silicone gel sheeting application for 3 months. Treatment outcome was recorded as recurrence or non-recurrence. In all patients, a follow-up period of minimum 12 months was required. Of these patients, 90.0% had successful treatment of their auricular keloids, whereas 10.0% had recurrences. The postoperative course was uneventful. In conclusion, our aesthetic reconstruction using a keystone flap created from the mastoid-helix area is a useful treatment strategy in terms of retroauricular keloids following conchal cartilage grafts.

Complete excision of proliferating core in auricular keloids significantly reduces local recurrence: A prospective study.

Keloids are mysterious soft-tissue tumors that are characterized by excessive reparative processes composed of collagen-forming fibroblasts and inflammatory cells. Generally, complete tumor excision regardless of sufficient margin is considered as a first-line treatment because they are considered reactive rather than a neoplastic condition. Recently, a specific part of the keloids is being highlighted as an important microstructure for local recurrence, but there has been very little evidence. We conducted a prospective study to evaluate the relationship of recurrence and several clinicopathological parameters with specific focus on surgical resection margin. A total 87 cases of auricular keloids from 71 patients were included. The resection margins were carefully evaluated by an exhaustive grossing method and thorough microstructural assessment. During up to 48.8 months of the follow-up period, local recurrence has been monitored and documented. The clinicopathological data including symptoms, bilaterality, size, location, prior treatment and operation history, gross type and etiology were collected and analyzed. Positive margin status was significantly related to tumor recurrence (P < 0.0001). Complete excision warrants a lower recurrence of auricular keloids in an Asian population. The most reasonable explanation for this seems to be remnant "proliferating core", which may serve a key role in local recurrence.

Could -79 °C Spray-Type Cryotherapy Be an Effective Monotherapy for the Treatment of Keloid?

Cryotherapy has been regarded as an effective modality for the treatment of keloids, and the spray-type device is one of the novel cryotherapeutic units. However, the biological mechanisms and therapeutic effects of this technique are incompletely studied. We evaluated the clinical efficacy of our cryotherapy protocol with molecular and pathologic evidence for the treatment of keloids. We evenly split each of ten keloid lesions into a non-treated (C-) and treated (C+) area; the C+ area was subjected to two freeze-thaw cycles of spray-type cryotherapy using -79 °C spray-type CryoPen™. This treatment was repeated after an interval of two weeks. The proliferation and migration abilities of the fibroblasts isolated from the dermis under the cryotherapy-treated or untreated keloid tissues (at least 5 mm deep) were compared and pathologic findings of the full layer were evaluated. Molecular analysis revealed that the number of dermal fibroblasts was significantly higher in C+ group as compared with C- group. The dermal fibroblasts from C+ group showed more than two-fold increase in the migration ability as compared with the fibroblasts from C- group. The expression of matrix metallopeptidase 9 was increased by more than two-fold and a significant increase in transforming growth factor beta 1 expression and Smad2/3 phosphorylation level was observed in C+ group. C+ group showed more extensive lymphoplasmacytic infiltration with thicker fibrosis and occasional "proliferating core collagen" as compared with C- group. Thus, -79 °C spray-type cryotherapy is ineffective as a monotherapy and should be used in combination with intralesional corticosteroids or botulinum toxin A for favourable outcomes in the treatment of thick keloids.

Establishment of Patient-Derived Keloid Xenograft Model.

Recent advances on preclinical model based on patient-derived tumor xenografts have new insight into many clinical fields. According to our literature review, many authors believe that immunodeficient animals such as athymic rats and mice should be used to prevent tissue loss caused by acute rejection to establish patient-derived tumor xenografts models.However, recent advances showed that the microenvironment has gained attention as an important factor responsible for disease progression. Additionally, researchers attempt to come up with novel findings in chemotherapy drugs and immune modulator to control development of keloid. For these reasons, establishment of reliable animal model of keloids is very important.In this new model using an immunocompetent animal as a humanized-xenografts model, human keloid scar has been maintained for as long as 4 months. Results of migration assay have demonstrated that typical morphology of keloid fibroblast was preserved based on multiple time point observations despite its aging change. Quantitative real time polymerase chain reaction findings suggested that after implantation, there has been significant increase of vascular endothelial growth factor, CD34, and transforming growth factor beta 1 expression despite insignificant changes of hypoxia inducible factor 1 an matrix metallopeptidase 1, and matrix metallopeptidase 9 gene expression. These findings suggested that implantation of keloids within the immunocompetent animals yields is very useful experimental model in terms of fibrosis.In summary, the authors have successfully established and propagated patient-derived keloid model using the immunocompetent animals. This model could be used to test novel materials as well as combination therapies and is superior to the conventional cell line experiment models. In addition, the biology of the keloids can easily be assessed to identify predictive markers for responses to treatment regimens that are currently actively under research in various centers.

Botulinum Toxin A Upregulates Rac1, Cdc42, and RhoA Gene Expression in a Dose-Dependent Manner: In Vivo and in Vitro Study.

UNLABELLED: Angiogenesis is the development of new capillaries from existing blood vessels and is a prerequisite for the wound-healing process. Many lines of scientific evidences have shown that complicated roles of small guanosine triphosphatases (GTPases) (ras-related C3 botulinum toxin substrate 1 [Rac1], cell division control protein 42 [Cdc42], and ras homolog gene family, member A [RhoA]) in regulation of signal transduction pathways exist to transmit distinct cellular effects on the modulation of actin cytoskeleton remodeling such as cell cycle progression, cell survival, and cell motility. In addition, these small GTPases activate mitogen-activated protein kinase kinase kinases (MAP3Ks) leading to activated mitogen-activated protein kinase kinases (MAPKK), mitogen-activated protein kinase (MAPK), and various transcription factors such as vascular endothelial growth factor with involvement of MAPK signaling pathways.In this study, the authors hypothesized that botulinum toxin A increases angiogenesis via the expression of small GTPases in vivo and in vitro studies.In vivo experiment, 24 Sprague-Dawley rats were randomly divided into 2 groups: a control group and a botulinum toxin A group. Five days prior to superiorly based transverse rectus abdominis myocutaneous flap elevation, the botulinum toxin A (BoTA) group was pretreated with BoTA, while the control group was pretreated with normal saline. quantitative real-time polymerase chain reaction was performed to evaluate the expression of Rac1, RhoA, and Cdc42.The angiogenic effects of botulinum toxin A on human dermal fibroblasts were measured in vitro experiment. To understand the mechanism of botulinum toxin A on small GTPases production of fibroblasts, Rac1, Cdc42, and RhoA were measured using qRT-PCR.The relative messenger ribonucleic acid expression of Rac1, RhoA, and Cdc42 was significantly higher in the BoTA group than in the control group, in every zone and pedicle muscle, on postoperative days 1, 3, and 5. Levels of these molecules increased significantly in human dermal fibroblasts grown in the presence of BoTA compared with control group over 5 IU.Our in vivo and in vitro studies suggest that administration of BoTA upregulates the expression of RhoA, Rac1, and Cdc42 in a dose-dependent manner. MAPK signaling pathway might be involved in BoTA-induced angiogenesis mechanism. LEVEL OF EVIDENCE: N/A.

Location of Keloids and Its Treatment Modality May Influence the Keloid Recurrence in Children.

BACKGROUND: Until now, clinical studies dealing with pediatric keloids are extremely rare considering widespread controversies over the mode of inheritance of keloids. To the best of the authors' knowledge, there have been no reports analyzing this condition systemically. The purpose of this study was to summarize the baseline characteristics of a cohort of pediatric patients and recommend our effective regimens. A total of 203 pediatric patients with keloid were treated at our hospital. METHODS: The authors retrospectively analyzed data including patient age, sex, etiology, anatomic location, previous treatment history and modalities, and etiology. Of the 203 patients, 167 (82.3%) were women and 36 (17.7%) were men. The average age was 15 years (interquartile range 12-18 years). The locations of our keloids in order of frequency were the ear, upper and lower extremities, shoulder and deltoid area, chest, abdomen and perineum, and face and neck. The number of patients treated for a primary keloid was 174 (85.7%), and remaining 29 patients (14.3%) were treated for a recalcitrant/recurrent keloid that failed to respond to other prior treatments. These prior treatments included single therapies such as steroid injection, excision, laser therapy, and a combination of excision with intralesional steroid injection. RESULTS: Of these patients, 88.6% had successful treatment of their keloids, whereas 11.4% had recurrences. Events of keloid recurrence were associated with anatomic areas and treatment modalities. Keloids occurring at lower extremity and chest areas have high propensity to recur even after completion of successful treatment. In addition, combination treatments such as surgical excision followed by full-thickness skin grafting and steroid injections, and surgical excision followed by steroid injections are also associated with high recurrence rate. CONCLUSIONS: The authors successfully treated pediatric keloids selecting proper regimen according to anatomic locations. Based on our study of 230 pediatric keloids, 2 characteristics were linked to the risk of keloid recurrence.

Histomorphometric analysis of collagen architecture of auricular keloids in an Asian population.

BACKGROUND: Keloids are a pathologic condition of the reparative process, which present as excessive scar formation that involves various cells and cytokines. Many studies focusing on the histologic feature of keloids, however, have shown discordant results without consideration of architectural aspect of collagen structure. OBJECTIVE: The purpose of this study was to demonstrate a schematic illustration of collagen architecture of keloids, specifically auricular keloids, and to analyze each part on the histomorphologic and morphometric basis. MATERIALS AND METHODS: Thirty-nine surgically excised auricular keloids were retrieved from the file of Kangbuk Samsung Hospital. After exhaustive histomorphologic analysis, 3 distinctive structural parts, keloidal collagen, organizing collagen, and proliferating core collagen, were identified and mapped in every case. Cellularity of fibroblasts, blood vessel density, degree of inflammatory cell infiltration, and mast cells counts using Masson trichrome stain, Van Gieson stain, toluidine blue stain, and immunohistochemical stains for CD31 and smooth muscle actin were analyzed in each part of each case. Morphometric analysis on these parameters using ImageJ software was performed using 3 representative images of each part. RESULTS: Three parts were histomorphologically distinct by shape and array of collagen bundles, fibroblasts cellularity, blood vessel density, degree of inflammatory cells, and mast cell infiltration. Morphometric analysis revealed statistically significant difference between each part in fibroblasts cellularity, blood vessel density, degree of inflammatory cell infiltration, and mast cells count. All parameters were exceedingly high in whorling hypercellular fibrous nodules in proliferating core collagen showing simultaneous changes in other parts. CONCLUSION: Morphologically and morphometrically, 3 distinctive parts were identified in auricular keloids. Mast cell infiltrations, blood vessel density, and fibroblast cellularity are simultaneously increased or decreased according to these parts. Proliferating core collagen might serve as a proliferating center of keloids and might be a key portion for tumor growth and recurrence.

Clinical implications of single- versus multiple-site keloid disorder: a retrospective study in an Asian population.

BACKGROUND: There is strong evidence of genetic susceptibility in individuals with keloid disorder. The purpose of this cross-sectional study was to determine the clinical relevance of our proposed variables on the multiplicity of keloids by further investigating the presence of other keloids and a family history. METHODS: This was a retrospective review, using institutional review board-approved questionnaires, of patients with keloids who were seen at Kangbuk Samsung Hospital between December 2002 and February 2010. Eight hundred sixty-eight patients were included in our study. Comparisons between the 2 groups were made using Mann-Whitney tests for continuous variables and χ2 tests for categorical variables. RESULTS: In our patient group, younger age of onset and the presence of family history were significantly associated with the occurrence of keloids at multiple sites. The locations of extra-auricular keloids, in order of frequency, included the shoulder; anterior chest, including the breasts; deltoid; trunk and pubic area; upper extremities; lower extremities; and other sites. As compared to secondary keloids, primary keloids were significantly associated with both a lower degree of recurrence and the presence of other keloids. The presence or absence of family history was significantly associated with the presence or absence of other keloids and primary or secondary keloids. CONCLUSIONS: Keloid disorder is one of the most frustrating problems in wound healing and advances in our understanding of the differences of occurrence at a single site versus multiple sites might help in understanding pathogenesis and improving treatment.

Histologic changes of implanted gore bio-a in an experimental animal model.

Gore Bio-A has been reported to be an ideal synthetic bioabsorbable scaffold material for hernia repair. The purpose of this study was to determine the effectiveness of Gore Bio-A in soft tissue augmentation. Six New Zealand white rabbits were used in the study. Five subcutaneous pockets were created on the back of the rabbit, and 20 × 20 mm sized square shaped Gore Bio-A sheets, each 1.5 mm, 3 mm, 4.5 mm, 6 mm, and 7.5 mm in thickness, were implanted into each pocket (1 layer to 5 layers). To analyze the morphologic and histologic changes, the implants were harvested 1, 3, and 6 months after implantation. Following the gross analysis, absorption rate was accelerated with increased implant duration and decreased thickness. Histological analysis of the implants demonstrated progressive neovascularization, fibroblast infiltration, and neocollagenation over time. Six months after implantation, Gore Bio-A was almost absorbed and degenerated, not maintaining its volume. Based on this study, Gore Bio-A was revealed as a biocompatible material; however, it is not suitable for soft tissue augmentation because it is absorbed in the process of changing into soft tissue without maintaining its own volume. Therefore, this material is incomplete and needs more study to overcome this limitation.

Methylene blue dye-induced skin necrosis in immediate breast reconstruction: evaluation and management.

BACKGROUND: For early breast cancer patients, skin-sparing mastectomy or nipple-sparing mastectomy with sentinel lymph node biopsy has become the mainstream treatment for immediate breast reconstruction in possible cases. However, a few cases of skin necrosis caused by methylene blue dye (MBD) used for sentinel lymph node localization have been reported. METHODS: Immediate breast reconstruction using a silicone implant was performed on 35 breasts of 34 patients after mastectomy. For sentinel lymph node localization, 1% MBD (3 mL) was injected into the subareolar area. The operation site was inspected in the postoperative evaluation. RESULTS: Six cases of immediate breast reconstruction using implants were complicated by methylene blue dye. One case of local infection was improved by conservative treatment. In two cases, partial necrosis and wound dehiscence of the incision areas were observed; thus, debridement and closure were performed. Of the three cases of wide skin necrosis, two cases underwent removal of the dead tissue and implants, followed by primary closure. In the other case, the breast implant was salvaged using latissimus dorsi musculocutaneous flap reconstruction. CONCLUSIONS: The complications were caused by MBD toxicity, which aggravated blood disturbance and skin tension after implant insertion. When planning immediate breast reconstruction using silicone implants, complications of MBD should be discussed in detail prior to surgery, and appropriate management in the event of complications is required.

Clinical features and outcomes of foot keloids treated using complete surgical excision and full thickness skin grafting followed by corticosteroid injections.

BACKGROUND: Keloids are often resistant to treatment and have high recurrence rates. To the best of the authors' knowledge, however, there have been very few case reports related to foot keloids. The purpose of this retrospective case-series was to summarize the baseline characteristics of a cohort of patients, introduce our treatment regimen for the successful treatment of foot keloids. METHODS: Patients were treated with surgical excision followed by full thickness skin grafting combined with postoperative steroid injections combined with silicone gel sheeting over a period of eight years from December 2004 to November 2012 at our institution. Subjective outcome was evaluated using Patient Scar Assessment Scales. The final objective outcome was judged by two independent physicians at the time of 12 months after treatment as recurrence or non-recurrence. RESULTS: Of 79 patients, 75 (94.9%) were women and 4 (5.1%) were men. The average age was 18 (range 7-43) years. The average pretreatment total size of the lesions was 50 (range 18-150) cm. The number of patients treated for a primary foot keloid was 29 (36.7%), and 70 patients (63.3%) were treated for a recurrent keloid that failed to respond to prior treatments. Prior treatments included single therapies such as surgical excision alone (4 patients, 5.1%), prior steroid injection alone (33 patients, 41.8%), and laser therapy (2 patients, 2.5%). Other therapies included combination treatments (11 patients, 13.9%). Most patients reported improved Patient Scar Assessment Scale by lapse of time. All patients completed the treatment regimen and follow-up of 12 months. Of these patients, 62 patients (78.5%) achieved successful treatment, while the remaining 17 (21.5%) experienced recurrence. CONCLUSIONS: We successfully treated foot keloids using complete surgical excision and full thickness skin grafting followed by four corticosteroid injections (at one month intervals).

The effects of sterilization methods on lyophilized cartilage grafts in an experimental model.

BACKGROUND: Cartilage graft is an effective method for reconstructing the bony framework of the face and covering the bony defect site. As a process method of cartilages, lyophilization has the advantages of long-term storage and easy handling. We hypothesized that the type of procedure used to sterilize lyophilized cartilage may affect outcomes after implantation into the body. We compared the effects of ethylene oxide (EO) gas, γ-irradiation, and autoclaving methods on cartilage grafts. METHODS: After sterilization, lyophilized human rib cartilage was inserted into subperiosteal pockets created in New Zealand white rabbit skulls. We assessed the weights and ratios of the remaining cartilage and examined histologic changes throughout the implantation period. RESULTS: Over a 5-week period, the γ-irradiated grafts remained more than the other grafts, but after more than 5 weeks, there were no significant differences between γ-irradiated and EO gas-sterilized cartilages. Autoclave-sterilized cartilages were totally resorbed at 10 weeks. CONCLUSIONS: Over 10 weeks of follow-up, based on persistence measurements and histologic appearance, there was little difference between γ-irradiated and EO gas-sterilized lyophilized cartilage used in experimental bone grafts.