記述言語：英語   掲載種別：研究論文（学術雑誌）  

UNLABELLED: Keloids are fibroproliferative lesions caused by abnormal dermal wound healing. Keloidal collagen (KC) is a pathognomic feature of keloids, but the mechanism by which it forms is unknown. This study aimed to evaluate the histopathology of KC and thereby gain clues into how it forms. METHODS: The cross-sectional study cohort consisted of a convenience series of patients with keloids who underwent surgical excision. Skin pieces (3 mm2) were collected from the keloid center and nearby control skin. Histopathology was conducted with light and electron microscopy and immunohistochemistry. KC composition was analyzed with protein shotgun analysis. RESULTS: Microscopic analyses revealed the ubiquitous close association between KC and αSMA-positive spindle-shaped cells that closely resembled myofibroblasts. Neither KC nor the spindle-shaped cells were observed in the control tissues. Compared with control skin, the collagen fibers in the KC were overall thinner, their diameter varied more, and their spacing was irregular. These features were particularly pronounced in the collagens in the vicinity of the spindle-shaped cells. Protein shotgun analysis did not reveal a specific collagen in KC but showed abnormally high abundance of collagens I, III, VI, XII, and XIV. CONCLUSIONS: These findings suggest that KC may be produced directly by myofibroblasts rather than simply being denatured collagen fibers. Because collagens VI and XII associate with myofibroblast differentiation, and collagen XIV associates with local mechanical stress, these collagens may reflect, and perhaps contribute to, the keloid-specific local conditions that lead to the formation of KC.

DOI： 10.1097/GOX.0000000000004897

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Pathological scars (including keloids, hypertrophic scars, and scar contractures) are present with high severity among certain populations, particularly in Asians and Africans who are highly prone to develop scars. Understanding the patho-mechanism that underlies scarring, such as mechanosignaling, systemic, and genetic factors, as well as optimal surgical techniques and integrated noninvasive therapeutic methods can guide clinicians to develop treatment protocols that can overcome these issues. This report summarizes a congress at Pacifico Yokohama (Conference Center) on December 19, 2021 involving researchers and clinicians from diverse disciplines who convened to discuss current clinical, preclinical, and most recent research advances in understanding pathological scarring, keloid and hypertrophic scar management, and research progress in wound healing. Presenters described the advances in scar therapies, understanding scarring mechanisms, and scar prevention and assessments tools. Moreover, presenters addressed the challenges during the COVID-19 pandemic and using telemedicine in management of scar patients.

DOI： 10.1097/GOX.0000000000004921

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記述言語：英語  

Fibroma of tendon sheath (FTS) is a rare soft tissue tumor that usually occurs in the upper extremity. Moreover, of the few cases reported in the feet, nearly all occur in the plantar region. We report the case of a large FTS in the dorsum of the left foot that grew quickly into a 4 cm-diameter lesion. The 44-year-old Japanese man noticed the tumor incidentally one year before presentation and could not recall any possible cause. Physical examination showed an elastic hard mass that spread over the third to fifth metatarsal bones. MRI showed iso-intense signals with central hypo-intensity on T1-weighted images and hypo-intense signals on T2-weighted images. Since a biopsy did not reveal any malignant findings, the lesion was excised surgically. The tumor was found to be multilocular, encapsulated, and to arise from the extensor digitorum brevis tendon. Histopathology showed scattered spindle fibroblasts and slit-like vascular structures within the dense collagenous matrix. The tumor was diagnosed on the basis of the clinical, demographic, surgical, and histopathological findings as an FTS arising from the extensor digitorum brevis tendon. A review of the literature revealed seven cases of FTS of the dorsum of the foot, which indicates its rarity. More than one-half of these cases were from Japan. While the cause of FTS remains unclear, trauma has been implicated. We suggest that the cultural background of the patient, which could promote kneeling-induced dorsal foot trauma, may have contributed to the onset/progression of our case. Level of Clinical Evidence: 4.

DOI： 10.1016/j.jpra.2022.11.005

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Keloids are laterally growing fibroproliferative skin disorders. Severe keloids spread widely, sometimes over joints, thus significantly limiting motor function. They are associated with recurrent, very painful draining infections. Here, we report a case of a giant keloid that was successfully treated by combination therapy comprising surgery (partial resection followed by local flap transposition) and subsequent radiotherapy and steroid-plaster therapy. The keloid was first noticed when the patient was 7 years old at the site of a Bacille Calmette-Guérin vaccination she had received on her left shoulder in infancy. The keloid grew rapidly and widely after adulthood. A malignant tumor was suspected at another hospital, but a biopsy at age 45 years indicated the lesion was a keloid. Later, the keloid grew from the shoulder onto the chest and back and over the anterior axilla. At age 62 years, the patient was referred to our hospital. Under general anesthesia, the keloid was partially resected and the wound was covered with a local flap. Postoperative radiotherapy was performed 1 week later. The residual keloid was treated for 18 months with steroid tape. At 18 months after surgery, no recurrence of the keloid was observed. The patient had no pain or movement restriction. She was extremely satisfied with the results and considered the treatment to have improved her quality of life. While a standard strategy for severe keloid remains to be established, combination therapy comprising surgery, postoperative radiotherapy, and steroid-plaster therapy that aims to reduce inflammation and skin tension may be an option.

DOI： 10.1272/jnms.JNMS.2022_89-610

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記述言語：英語  

INTRODUCTION: We encountered an extremely rare case of a vesicocutaneous fistula due to vesical diverticulitis with stones. CASE PRESENTATION: A 78-year-old male patient presented to our department with complaints of suppurative discharge in the suprapubic area. Computed tomography revealed an enlarged prostate, a vesical diverticulum with stones located on the ventral side, and an aberrant connection between the anterior bladder wall and the external surface of the skin. The patient was diagnosed with a vesicocutaneous fistula due to vesical diverticulitis and was successfully treated with a multidisciplinary approach including vesical diverticulectomy with stone removal and nonviable tissue debridement. The patient continues to receive regular outpatient follow-ups with urinary catheter changes. CONCLUSION: Vesicocutaneous fistulas due to vesical diverticulitis with stones are extremely rare. We should be aware that a vesical diverticulum with stones located on the ventral side might pose a high-risk factor for the formation of a vesicocutaneous fistula in elderly patients.

DOI： 10.1002/iju5.12546

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Dermatofibroma is a common benign skin lesion with a contested etiology: some believe it is a neoplasm while others propose minor injuries initiate it. Many dermatofibroma variants have been described, including keloidal dermatofibroma, which is unusual by bearing keloidal collagen. Keloidal dermatofibroma was first described in 1998 and only 15 cases have been reported. Since keloids are driven by skin injuries, the existence of keloidal dermatofibroma has been suggested to support the injury hypothesis of dermatofibroma etiology. To better understand keloidal dermatofibroma characteristics and gain clues regarding dermatofibroma etiology, consecutive keloidal dermatofibroma cases (n = 52) and dermatofibroma without keloidal collagen (n = 2077) that were histopathologically diagnosed in 2016-2019 were identified from the records of a Japanese dermatopathology laboratory and compared in terms of demographic, clinical, and histopathological characteristics by univariate analyses. Compared to other dermatofibromas, keloidal dermatofibromas occurred more frequently on the forearm and hand (P < 0.0001 and 0.0019), especially the wrist dorsum, and in the superficial skin layer (P < 0.0001). Keloidal dermatofibromas also demonstrated more cellularity and hemorrhage (both P < 0.0001). Correlation analyses between keloidal collagen amount and keloidal dermatofibroma size (a proxy of time-since-onset) did not support the notion that keloidal collagen deposition and keloidal dermatofibroma formation are triggered simultaneously. Recent injury, as indicated by fresh hemorrhage, was equally common in putatively older and younger keloidal dermatofibromas. Thus, keloidal collagen in keloidal dermatofibromas could be due to injury to preexisting dermatofibromas, which suggests that the keloidal dermatofibroma entity does not prove the injury hypothesis. Commonalities between keloids and keloidal dermatofibromas suggest a link between genetics, provocative events that induce myofibroblast differentiation, and keloidal collagen production.

DOI： 10.1111/1346-8138.16638

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Key risk factors for hypertrophic scarring and surgical-site infections are high-tension wounds, fat necrosis, and dead space. All could be prevented by appropriate superficial fascia suturing. However, the as-yet poorly researched anatomy of the superficial fascia should be delineated. This study is the first to quantify the superficial fascia throughout the human body in vivo. METHODS: Ultrasound was used to analyze the superficial and deep fascia of 10 volunteers at 73 points on 11 body regions, including the upper and lower trunk and limbs. Number, thickness and percentage of superficial fascia layers, and deep fascia and dermis thickness, were measured at each point. RESULTS: Seven hundred thirty ultrasound images were analyzed. Body regions varied markedly in terms of subcutaneous variables. Posterior chest had the thickest deep fascia and dermis and the highest average superficial fascia layer thickness [0.6 mm (95 percent CI, 0.6 to 0.7 mm)]. Anterior chest had the most superficial fascia layers [3.7 (95 percent CI, 3.5 to 3.8)]. Posterior and anterior chest had among the highest percentage of superficial fascia. Abdomen and especially gluteus had a low percentage of superficial fascia. Covariate analyses confirmed that posterior and anterior chest generally had higher superficial fascia content than gluteus and abdomen (both p < 0.001). They also showed that the dermis in the posterior and anterior chest increased proportionally to total fascia thickness. CONCLUSIONS: The superficial fascia, deep fascia, and dermis tend to be thick in high-tension areas such as the upper trunk. A site-specific surgical approach is recommended for subcutaneous sutures. CLINICAL RELEVANCE STATEMENT: Understanding the anatomical distribution of the superficial fascia and deep fascia will help surgeons optimize subcutaneous fasciae suturing, thereby potentially reducing the incidence of surgical-site infections and hypertrophic scars.

DOI： 10.1097/PRS.0000000000009631

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

UNLABELLED: Keloids are red' invasive scars that are driven by chronic inflammation in the reticular dermis. The role of blood vessels in keloid behavior remains poorly understood. In the present study with 32 keloid patients, we examined the hemodynamics of keloid tissue, the anatomy of the blood vessels feeding and draining the keloids, and the vascular histology of keloids. METHODS: Ten patients with large anterior chest keloids underwent near-infrared spectroscopy, which measured regional saturation of oxygen and total hemoglobin index in the keloid and surrounding skin. Another 10 patients with large chest keloids and three healthy volunteers underwent multidetector-low computed tomography. The extirpated chest keloids of 12 patients were subjected to histology with optical, CD31 immunohistochemical, and electron microscopy. RESULTS: All keloids had a low regional saturation of oxygen and a high total hemoglobin index, which is indicative of blood congestion. Multidetector-low computed tomography revealed dilation of the arteries and veins that were respectively feeding and draining the keloid leading edge. Hematoxylin-eosin staining and CD31 immunohistochemisty revealed considerable neovascularization in the keloid leading edge but not in the center. Electron microscopy showed that the lumens of many vessels in the keloid center appeared to be occluded or narrowed. CONCLUSIONS: Keloids seem to be congested because of increased neovascularization and arterial inflow at the leading edge and blocked outflow due to vascular destruction in the center. The surrounding veins seem to expand in response to this congested state. Methods that improve the blood circulation in keloids may be effective therapies.

DOI： 10.1097/GOX.0000000000004374

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出版者・発行元：Cold Spring Harbor Laboratory  

Abstract

For decades, it has been assumed that the foreign body response (FBR) to biomedical implants is primarily a reaction to the chemical and mechanical properties of the implant. Here, we show for the first time that a third independent variable, allometric tissue-scale forces (which increase exponentially with body size), can drive the biology of FBR in humans. We first demonstrate that pathological FBR in humans is mediated by immune cell-specific Rac2 mechanotransduction signaling, independent of implant chemistry or mechanical properties. We then show that mice, which are typically poor models of human FBR, can be made to induce a strikingly human-like pathological FBR by altering these extrinsic tissue forces. Altering these extrinsic tissue forces alone activates Rac2 signaling in a unique subpopulation of immune cells and results in a human-like pathological FBR at the molecular, cellular, and local tissue levels. Finally, we demonstrate that blocking Rac2 signaling negates the effect of increased tissue forces, dramatically reducing FBR. These findings highlight a previously unsuspected mechanism for pathological FBR and may have profound implications for the design and safety of all implantable devices in humans.

One-Sentence Summary

Allometric tissue-scale forces at the implant-tissue interface drive pathological foreign body response.

DOI： 10.1101/2022.01.14.476395

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Tissue repair and healing remain among the most complicated processes that occur during postnatal life. Humans and other large organisms heal by forming fibrotic scar tissue with diminished function, while smaller organisms respond with scarless tissue regeneration and functional restoration. Well-established scaling principles reveal that organism size exponentially correlates with peak tissue forces during movement, and evolutionary responses have compensated by strengthening organ-level mechanical properties. How these adaptations may affect tissue injury has not been previously examined in large animals and humans. Here, we show that blocking mechanotransduction signaling through the focal adhesion kinase pathway in large animals significantly accelerates wound healing and enhances regeneration of skin with secondary structures such as hair follicles. In human cells, we demonstrate that mechanical forces shift fibroblasts toward pro-fibrotic phenotypes driven by ERK-YAP activation, leading to myofibroblast differentiation and excessive collagen production. Disruption of mechanical signaling specifically abrogates these responses and instead promotes regenerative fibroblast clusters characterized by AKT-EGR1.

DOI： 10.1038/s41467-021-25410-z

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Neovascularization plays a critical role in skin graft survival. Up to date, the lack of specificity to solely track the newly sprouting blood vessels has remained a limiting factor in skin graft transplantation models. Therefore, the authors developed a new model by using Flt1-tdsRed BAC transgenic mice. Flt1 is a vascular endothelial growth factor receptor expressed by sprouting endothelial cells mediating neoangiogenesis. The authors determined whether this model reliably visualizes neovascularization by quantifying tdsRed fluorescence in the graft over 14 days. METHODS: Cross-transplantation of two full-thickness 1 × 1-cm dorsal skin grafts was performed between 6- to 8-week-old male Flt1 mice and KSN/Slc nude mice (n = 5). The percentage of graft area occupied by tdsRed fluorescence in the central and lateral areas of the graft on days 3, 5, 9, and 14 was determined using confocal-laser scanning microscopy. RESULTS: Flt1+ endothelial cells migrating from the transgenic wound bed into the nude graft were first visible in the reticular dermis of the graft center on day 3 (0.5 ± 0.1; p < 0.05). Peak neovascularization was observed on day 9 in the lateral and central parts, increasing by 2- to 4-fold (4.6 ± 0.8 and 4.2 ± 0.9; p < 0.001). Notably, some limited neoangiogenesis was displayed within the Flt grafts on nude mice, particularly in the center. No neovascularization was observed from the wound margins. CONCLUSION: The ability of the Flt1-tdsRed transgenic mouse model to efficiently identify the origin of the skin-graft vasculature and visualize graft neovascularization over time suggests its potential utility for developing techniques that promote graft neovascularization.

DOI： 10.1097/PRS.0000000000008039

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記述言語：英語  

We previously reported cases of anterior-neck reconstruction using super-thin and perforator-supercharged skin-pedicled flaps harvested from the pectoral area and back. Here, we reconstructed a neck-scar contracture with a long skin-pedicled flap from the pectoral area that survived without congestion despite not being supercharged with a perforator, as planned. The patient, a 67-year-old man, was admitted to our hospital due to neck-scar contracture after a chemical burn 3 years previously. During surgery, the scar was resected above the platysma. A large, 19 × 6-cm skin-pedicled flap was elevated from the left pectoral area. We planned to supercharge the flap by anastomosing the second intercostal perforator to the flap periphery but could not confirm the perforator intraoperatively. To promote flap survival, we did not elevate the flap pedicle more than absolutely necessary and then manipulated the flap very carefully. The flap survived fully and the contracture was effectively released. Thin flaps are useful for reconstructing exposed areas such as the face, neck, and dorsum of the hands that require good outcomes in terms of both function and aesthetics. However, if the flap is too large, ischemia/congestion could arise in the periphery unless the blood flow is stabilized by attaching a perforator. In our case, supercharging was not possible and we had to resort to careful intraoperative maneuvers to ensure flap survival. This approach was successful and suggests that although supercharging of thin and large flaps is preferred, unexpectedly unsuperchargeable flaps can be rescued by careful and finely tuned surgical judgment and techniques.

DOI： 10.1097/GOX.0000000000003404

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: A universally accepted therapeutic strategy for umbilical keloids has not been determined. Our team has had considerable success with combination therapy composed of surgical excision followed by postoperative radiotherapy and steroid plaster/injection. Methods: All consecutive patients with umbilical keloids that developed from endoscopic surgical scars and underwent minimal-margin keloid excision followed by umbilicoplasty with a flap if needed, tension-reduction suturing, and postoperative radiotherapy in 2013-2017 in the keloid/scar-specialized clinic at the Department of Plastic, Reconstructive and Aesthetic Surgery of Nippon Medical School. The postsurgical radiotherapy regimen was 15 Gy administered in 2 fractions over 2 consecutive days. Radiotherapy was followed by tension-reducing wound self-management with silicone tape or, if needed, steroid plaster. The primary study focus was keloid recurrence during the 24-month follow-up period. Recurrence was defined as the growth of stiff red lesions in even small areas of the scar that was refractory to 2-6 months of steroid-plaster therapy. Results: The case series consisted of 34 patients with 34 lesions. Three lesions (8.8%) recurred. One recurrence was successfully treated by concomitant steroid plaster/injection. The other 2 cases were resistant to steroid injection and underwent reoperation without radiotherapy followed by 6 months of steroid-plaster therapy. None of the 3 cases recurred within 2 years of steroid plaster/injection completion or reoperation. Conclusion: Umbilical keloids can be successfully treated by customized treatment plans that involve appropriate surgical modalities (including umbilicoplasty, if required), postoperative radiotherapy (15 Gy/2 fractions/2 days), and wound/scar self-management with silicone tape and steroid plaster.

DOI： 10.1097/GOX.0000000000003181

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Hypertrophic scars (HSs) and keloids are histologically characterized by excessive extracellular matrix (ECM) deposition. ECM deposition depends on the balance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteases (TIMPs). TIMP-1 has been linked to ECM degradation and is therefore a promising therapeutic strategy. In this study, we generated super carbonate apatite (sCA) nanoparticle-encapsulated TIMP-1 small interfering RNA (siRNA) (siTIMP1) preparations and examined the effect of local injections on mouse HSs and on ex vivo-cultured keloids. The sCA-siTIMP1 injections significantly reduced scar formation, scar cross-sectional areas, collagen densities, and collagen types I and III levels in the lesions. None of the mice died or exhibited abnormal endpoints. Apatite accumulation was not detected in the other organs. In an ex vivo keloid tissue culture system, sCA-siTIMP1 injections reduced the thickness and complexity of collagen bundles. Our results showed that topical sCA-siTIMP1 injections during mechanical stress-induced HS development reduced scar size. When keloids were injected three times with sCA-siTIMP1 during 6 days, keloidal collagen levels decreased substantially. Accordingly, sCA-siRNA delivery may be an effective approach for keloid treatment, and further investigations are needed to enable its practical use.

DOI： 10.1016/j.omtn.2020.08.005

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

In 2006, we established a scar/keloid-specialized institution in the Department of Plastic, Reconstructive, and Aesthetic Surgery at Nippon Medical School (NMS) in Tokyo, Japan. In the ensuing 15 years, we treated approximately 2000 new scar/keloid patients annually. This extensive experience has greatly improved the efficacy of the treatments we offer. Therefore, we discuss here the latest NMS protocol for preventing and treating keloids and hypertrophic scars. While this protocol was optimized for Japanese patients, our experiences with a growing body of international patients suggest that it is also effective in other ethnicities. The extensive evidence-based experience underlying the NMS protocol suggests that it may be suitable as the foundation of a standard international prevention/treatment algorithm for pathological scars.

DOI： 10.1272/jnms.JNMS.2021_88-106

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Severe keloids are currently treated with surgical resection followed by radiation. Radiotherapy is essential for preventing recurrences. Fascia tensile reduction suturing may also prevent recurrence. We asked whether superficial fascia tensile reduction with or without deep fascia tensile reduction reduced skin mechanical tension and yielded good outcomes. METHODS: Geometric modeling on 3-dimensional anatomic shapes assessed the effect of superficial fascia tensile reduction with or without deep fascia tensile reduction on skin tension. A retrospective cohort study was performed on patients with severe anterior-chest keloids with Japan Scar Workshop-scar scale classification score ≥ 16 who underwent resection plus fascia tensile reduction plus radiotherapy between 2011 and 2016 and were followed for >18 months. Patient characteristics and 18-month postoperative outcomes were examined. Postoperative outcome was defined as rates of keloid disappearance, improvement, and obvious recurrence. RESULTS: Maximal mechanical forces placed on the dermis by dermal sutures, dermal sutures plus superficial fascia tensile reduction, and dermal sutures plus superficial fascia tensile reduction plus deep fascia tensile reduction were 4,700, 573, and 697 Pa, respectively. Adding deep fascia tensile reduction to superficial fascia tensile reduction decreased the force on the superficial fascia. Of 77 cohort patients, 27 and 50 underwent superficial fascia tensile reduction and superficial fascia tensile reduction plus deep fascia tensile reduction, respectively. Superficial fascia tensile reduction plus deep fascia tensile reduction patients underwent complete excision more often (60.0% vs 37.0%, P = .046). The groups did not differ in 18-month surgical outcome, including recurrence rate (P = .670). CONCLUSION: Our 2003 study showed that in anterior-chest keloids, resection plus non-fascial suturing plus radiotherapy led to a 43.1% recurrence. Thus, fascia tensile reduction suturing helps reduce anterior-chest keloid recurrence to ∼5.2%. Superficial fascia tensile reduction plus deep fascia tensile reduction is suitable for relatively large keloids that require total resection. Deep fascia tensile reduction may facilitate superficial fascia tensile reduction but may only be useful when it is technically difficult to achieve reduction with superficial fascia tensile reduction alone.

DOI： 10.1016/j.surg.2019.07.028

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Wound healing is a complex biological process, and imbalances of various substances in the wound environment may prolong healing and lead to excessive scarring. Keloid is abnormal proliferation of scar tissue beyond the original wound margins with excessive deposition of extracellular matrix (ECM) and chronic inflammation. Despite numerous previous research efforts, the pathogenesis of keloid remains unknown. Vascular endothelial cells (VECs) are a major type of inductive cell in inflammation and fibrosis. Despite several studies on vascular morphology in keloid formation, there has been no functional analysis of the role of VECs. In the present study, we isolated living VECs from keloid tissues and investigated gene expression patterns using microarray analysis. We obtained 5 keloid tissue samples and 6 normal skin samples from patients without keloid. Immediately after excision, tissue samples were gently minced and living cells were isolated. Magnetic-activated cell sorting of VECs was performed by negative selection of fibroblasts and CD45+ cells and by positive selection of CD31+cells. After RNA extraction, gene expression analysis was performed to compare VECs isolated from keloid tissue (KVECs) with VECs from normal skin (NVECs). After cell isolation, the percentage of CD31+ cells as measured by flow cytometry ranged from 81.8%-98.6%. Principal component analysis was used to identify distinct molecular phenotypes in KVECs versus NVECs and these were divided into two subgroups. In total, 15 genes were upregulated, and 3 genes were downregulated in KVECs compared with NVECs using the t-test (< 0.05). Quantitative RT-PCR and immunohistochemistry showed 16-fold and 11-fold overexpression of SERPINA3 and LAMC2, respectively. SERPINA3 encodes the serine protease inhibitor, α1-antichymotripsin. Laminin γ2-Chain (LAMC2) is a subunit of laminin-5 that induces retraction of vascular endothelial cells and enhances vascular permeability. This is the first report of VEC isolation and gene expression analysis in keloid tissue. Our data suggest that SERPINA3 and LAMC2 upregulation in KVECs may contribute to the development of fibrosis and prolonged inflammation in keloid. Further functional investigation of these genes will help clarify the mechanisms of abnormal scar tissue proliferation.

DOI： 10.3389/fcell.2020.00658

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Therapies for upper arm keloids include surgical excision followed by postoperative radiotherapy, silicone tape stabilization, and steroid plaster. However, a universally accepted therapeutic strategy for upper-arm keloids is lacking. Methods: All consecutive patients with single upper-arm keloids who underwent keloid excision followed by tension-reducing suturing, multiple z-plasties, and postoperative radiotherapy in 2013-2016 in the keloid/scar specialist clinic at the Department of Plastic, Reconstructive and Aesthetic Surgery of Nippon Medical School, were included in this case series study. Only keloids that arose from the small injury produced during Bacillus Calmette-Guérin vaccination were selected. The postsurgical radiotherapy regimen was 18 Gy administered in 3 fractions over 3 days. Radiotherapy was followed by tension-reducing wound self-management with silicone tape and, if needed, steroid plaster. The primary study objective was keloid recurrence during the 24-month follow-up period. Recurrence was defined as the growth of stiff red lesions in even small areas of the scar that was refractory to at least 2 months of steroid plaster therapy. Results: In total, 38 patients with 38 lesions were enrolled. Two lesions (5.3%) recurred. Both recurrences were successfully treated by concomitant steroid plaster and steroid injection. The recurrence patients were significantly more likely than the nonrecurrence patients to have multiple keloids. The 2 groups did not differ in terms of original keloid size. Conclusions: Upper-arm keloids can be successfully treated by customized plans that involve appropriate surgical modalities (including multiple z-plasties), postoperative radiotherapy (18 Gy/3 fractions/3 d), and postoperative wound/scar self-management with silicone tape and steroid plaster.

DOI： 10.1097/GOX.0000000000002496

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Fibroproliferative disorders result in excessive scar formation, are associated with high morbidity, and cost billions of dollars every year. Of these, keloid disease presents a particularly challenging clinical problem because the cutaneous scars progress beyond the original site of injury. Altered mechanotransduction has been implicated in keloid development, but the mechanisms governing scar progression into the surrounding tissue remain unknown. The role of mechanotransduction in keloids is further complicated by the differential mechanical properties of keloids and the surrounding skin. METHODS: The authors used human mechanical testing, finite element modeling, and immunohistologic analyses of human specimens to clarify the complex interplay of mechanical stress, strain, and stiffness in keloid scar progression. RESULTS: Changes in human position (i.e., standing, sitting, and supine) are correlated to dynamic changes in local stress/strain distribution, particularly in regions with a predilection for keloids. Keloids are composed of stiff tissue, which displays a fibrotic phenotype with relatively low proliferation. In contrast, the soft skin surrounding keloids is exposed to high mechanical strain that correlates with increased expression of the caveolin-1/rho signaling via rho kinase mechanotransduction pathway and elevated inflammation and proliferation, which may lead to keloid progression. CONCLUSIONS: The authors conclude that changes in human position are strongly correlated with mechanical loading of the predilection sites, which leads to increased mechanical strain in the peripheral tissue surrounding keloids. Furthermore, increased mechanical strain in the peripheral tissue, which is the site of keloid progression, was correlated with aberrant expression of caveolin-1/ROCK signaling pathway. These findings suggest a novel mechanism for keloid progression.

DOI： 10.1097/PRS.0000000000005717

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Reactive oxygen species (ROS) impair wound healing through destructive oxidation of intracellular proteins, lipids and nucleic acids. Intracellular superoxide dismutase (SOD1) regulates ROS levels and plays a critical role in tissue homoeostasis. Recent evidence suggests that age-associated wound healing impairments may partially result from decreased SOD1 expression. We investigated the mechanistic basis by which increased oxidative stress links to age-associated impaired wound healing. Fibroblasts were isolated from unwounded skin of young and aged mice, and myofibroblast differentiation was assessed by measuring α-smooth muscle actin and collagen gel contraction. Excisional wounds were created on young and aged mice to study the healing rate, ROS levels and SOD1 expression. A mechanistic link between oxidative stress and fibroblast function was explored by assessing the TGF-β1 signalling pathway components in young and aged mice. Age-related wounds displayed reduced myofibroblast differentiation and delayed wound healing, consistent with a decrease in the in vitro capacity for fibroblast-myofibroblast transition following oxidative stress. Young fibroblasts with normal SOD1 expression exhibited increased phosphorylation of ERK in response to elevated ROS. In contrast, aged fibroblasts with reduced SOD1 expression displayed a reduced capacity to modulate intracellular ROS. Collectively, age-associated wound healing impairments are associated with fibroblast dysfunction that is likely the result of decreased SOD1 expression and subsequent dysregulation of intracellular ROS. Strategies targeting these mechanisms may suggest a new therapeutic approach in the treatment of chronic non-healing wounds in the aged population.

DOI： 10.1111/exd.13404

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: The therapies for anterior chest wall keloids include surgical excision, postoperative radiotherapy, silicone taping stabilization, and steroid plaster. However, to date, there is no universally accepted combination treatment strategy for anterior chest wall keloids. Methods: All consecutive patients with single or multiple anterior chest wall keloids who underwent keloid excision, tension-reducing suturing, z-plasty, and postoperative radiotherapy in 2013-2016 in Nippon Medical School were included in this case series study. Only keloids that arose from small injuries such as folliculitis or acne were selected. The surgery was followed by tension-reducing self-management of the wounds with silicone tape and steroid plaster. The postsurgical radiotherapy modality was 18 Gy administered in 3 fractions over 3 days. The primary study outcome was keloid recurrence during the 24-month follow-up period. Recurrence was defined as the development of stiff and red lesions in even a small part of the scar that did not respond to 6 months of steroid plaster therapy. Results: In total, 141 patients with 141 lesions were enrolled. Of the 141 lesions, 15 (10.6%) recurred. All recurrences were successfully treated by steroid plaster and steroid injection. The recurrence patients did not differ from the nonrecurrence patients in terms of the size of the original keloid or gender distribution. Conclusions: Anterior chest wall keloids can be successfully treated by customized plans that involve appropriate surgical modalities (including z-plasty) followed by postoperative radiotherapy (18 Gy in 3 fractions over 3 days) and scar self-management with silicone tape and steroid plaster.

DOI： 10.1097/GOX.0000000000002177

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

There has been a long-standing need for guidelines on the diagnosis and treatment of keloids and hypertrophic scars that are based on an understanding of the pathomechanisms that underlie these skin fibrotic diseases. This is particularly true for clinicians who deal with Asian and African patients because these ethnicities are highly prone to these diseases. By contrast, Caucasians are less likely to develop keloids and hypertrophic scars, and if they do, the scars tend not to be severe. This ethnic disparity also means that countries vary in terms of their differential diagnostic algorithms. The lack of clear treatment guidelines also means that primary care physicians are currently applying a hotchpotch of treatments, with uneven outcomes. To overcome these issues, the Japan Scar Workshop (JSW) has created a tool that allows clinicians to objectively diagnose and distinguish between keloids, hypertrophic scars, and mature scars. This tool is called the JSW Scar Scale (JSS) and it involves scoring the risk factors of the individual patients and the affected areas. The tool is simple and easy to use. As a result, even physicians who are not accustomed to keloids and hypertrophic scars can easily diagnose them and judge their severity. The JSW has also established a committee that, in cooperation with outside experts in various fields, has prepared a Consensus Document on keloid and hypertrophic scar treatment guidelines. These guidelines are simple and will allow even inexperienced clinicians to choose the most appropriate treatment strategy. The Consensus Document is provided in this article. It describes (1) the diagnostic algorithm for pathological scars and how to differentiate them from clinically similar benign and malignant tumors, (2) the general treatment algorithms for keloids and hypertrophic scars at different medical facilities, (3) the rationale behind each treatment for keloids and hypertrophic scars, and (4) the body site-specific treatment protocols for these scars. We believe that this Consensus Document will be helpful for physicians from all over the world who treat keloids and hypertrophic scars.

DOI： 10.1186/s41038-019-0175-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Keloids can be treated in a number of ways, including by surgery. Multiple studies now show that while surgical monotherapy associates with extremely high rates of recurrence (50%-80%), postoperative radiotherapy can significantly reduce these recurrence rates. Ongoing improvements in radiation technology have further increased the safety and efficacy of this combination protocol. Of the various radiotherapies that have been used in this setting, electron beam (β-ray) irradiation is currently the best due to its excellent dose distribution and safety. The maximal biologically effective dose (BED) for keloids is 30 Gy (using an estimated α / β ratio of 10); increasing the dose has no further benefits and elevates side effects. Over the last two decades, we have modified and then fine-tuned our radiotherapy protocol for keloid excision wounds. Thus, our early protocol was used for all body sites and consisted of 15 Gy/3 fr/3 days. We then customised the radiotherapy protocol so that body sites that are highly prone to recurrence (e.g. the anterior chest) receive higher doses while low recurrence sites like the earlobe receive a much smaller dose. More recently, we tweaked this body site-customised protocol so that fewer fractions are employed. Therefore, we currently apply 18 Gy/3 fr/3 days to high-recurrence sites, 8 Gy/1 fr/1 day to earlobes and 15 Gy/2 fr/2 days to other body sites. These radiotherapy protocol changes were accompanied by the evolution of body site-customised surgical approaches. As a result of these developments, our overall keloid recurrence rate is now below 10%.

DOI： 10.1177/2059513119891113

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

It is difficult to completely resect huge anterior chest wall keloids and then close the wound directly. We report here our retrospective analysis of our case series of patients with such keloids who underwent reconstruction with internal mammary artery perforator (IMAP) pedicled propeller flaps and then received postoperative high-dose-rate superficial brachytherapy. METHODS: All consecutive patients with large/severe keloids on the anterior chest wall who underwent keloid resection followed by reconstruction with IMAP-pedicled propeller flaps and then high-dose-rate superficial brachytherapy in our academic hospital were identified. All cases were followed for >18 months. Donor site position, perforator pedicle, flap size, angle of flap rotation, complications, and recurrence were documented. RESULTS: There were nine men and one woman. The average age was 37.9 years. The average follow-up duration was 28.7 months. The largest flap was 16 × 4 cm. The dominant perforators of the internal mammary artery were located in the sixth (n = 2), seventh (n = 5), eighth (n = 1), and ninth (n = 2) intercostal spaces. Twelve months after surgery, patients reported marked relief from keloid-associated pain and itching, except in two patients who underwent partial keloid resection; their remaining keloids were still troublesome but after conservative therapies, including steroid ointments/plasters, the keloids gradually ameliorated. Eighteen months after surgery, there was no keloid recurrence or new development of keloids on the donor site. CONCLUSIONS: IMAP-pedicled propeller flaps transfer skin tension from the anterior chest wall to the abdomen. Our series suggests that this approach combined with radiation therapy can control keloid recurrence.

DOI： 10.1097/GOX.0000000000001049

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Keloids are characterized by the formation of excessive scar tissue that extends beyond the area of the initial wound. Keloid redness is due to angiogenesis and chronic inflammation and is an important indicator of the severity of the lesion and the effectiveness of treatment. METHODS: The color of 33 untreated keloids from 30 patients was measured with a narrow-band reflectance colorimeter. The erythema and melanin levels in the keloids (Ek and Mk, respectively) were recorded with control data obtained from the flexor aspect of the forearm (Ec and Mc, respectively). The keloid color was also evaluated subjectively. RESULTS: The Ek or Mk values did not vary significantly according to symptom intensity, scar region, patient age, and patient sex. Younger patients (<40 years) and female patients had significantly higher Ek/Ec ratios than did older patients and male patients, respectively. Subjective keloid redness evaluations distinguished keloids with high Ek/Ec ratios from keloids with low Ek/Ec ratios (P<0.0001) but could not distinguish keloids with high Ek from keloids with low Ek. CONCLUSIONS: Subjective evaluations of keloids in Japanese subjects reflected Ek/Ec ratios, which were strongly affected by variation in background skin color. The subjective assessment of the color of keloids or other skin disorders should be performed with caution in Asian populations.

DOI： 10.1272/jnms.83.142

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Keloids are defined as a kind of dermal fibroproliferative disorder resulting from the accumulation of collagen. In the remodeling of extracellular matrix, the balance between matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs) is as critical as the proper production of extracellular matrix. We investigate the role of TIMPs and MMPs in the pathogenesis of keloids and examine the therapeutic potential of TIMP-2. METHODS: The expression of TIMPs and MMPs in most inflamed parts of cultured keloid fibroblasts (KFs) and peripheral normal skin fibroblasts (PNFs) in the same individuals and the reactivity of KFs to cyclic mechanical stretch were analyzed by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay (n = 7). To evaluate the effect of treating KFs with TIMP-2, collagen synthesis was investigated by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay, and microscopic analysis was used to examine the treatment effects of TIMP-2 on ex vivo cultures of keloid tissue (n = 6). RESULTS: TIMP-2 was downregulated in cultured KFs compared with PNFs in the same individuals, and the reduction in TIMP-2 was exacerbated by cyclic mechanical stretch. Administration of TIMP-2 (200 or 300 ng/mL) significantly suppressed expression of Col1A2 and Col3A1 mRNA and collagen type I protein in KFs. TIMP-2 also significantly reduced the skin dermal and collagen bundle thickness in ex vivo cultures of keloid tissue. CONCLUSION: These results indicated that downregulation of TIMP-2 in KFs is a crucial event in the pathogenesis of keloids, and the TIMP-2 would be a promising candidate for the treatment of keloids.

DOI： 10.1097/GOX.0000000000000503

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

BACKGROUND: Treatments for keloids on the cartilaginous part of the auricle (i.e., the upper part of the ear excluding the earlobe) include surgical excision, cryosurgery, postoperative radiation therapy, steroid injection, taping stabilization, and pressure therapy. However, to date, there is no universally accepted treatment strategy for auricle keloids. METHODS: In this retrospective cohort study, the 63 primary auricle keloids in all 57 patients who underwent surgery from 2006 to 2012 were included. Mild scars such as hypertrophic scars were excluded. All 63 scars were treated with surgery, namely, total excision or intralesional excision (core excision method), and postoperative adjuvant radiation therapy and self-managed scar stabilization with surgical tape. The postsurgical radiation therapy consisted of 15 Gy administered in three fractions over 3 days. The recurrence rates associated with the two surgical methods over 18 months of follow-up were recorded. RESULTS: Of the 57 patients, 91.2 percent were women. Of the 63 lesions, 95.2 percent and 4.8 percent were caused by piercing and trauma, respectively. All were primary keloids. Before 2009, all lesions (n = 37) were treated by total excision. After 2009, all lesions (n = 26) were treated by core excision. These methods were associated with recurrence rates of 8.1 percent and 0 percent, respectively, although this difference did not achieve statistical significance (p > 0.05). The overall recurrence rate was 4.8 percent. Complications such as wound dehiscence and pigmentation during the 18-month follow-up period were not observed. CONCLUSION: Auricle keloids can be treated by customized plans consisting of appropriate surgical modalities, postoperative radiotherapy, and self-management. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

DOI： 10.1097/PRS.0000000000000962

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The present retrospective cohort study was performed to determine the efficacy of contact-mode 1064 nm neodymium-yttrium-aluminum-garnet (Nd:YAG) laser laser for keloids and hypertrophic scars. The indication and limitations of this modality are discussed. METHODS: The cohort consisted of 102 consecutive Japanese patients (23 males and 79 females) with keloids and hypertrophic scars for more than 1 year. They were treated every 3-4 weeks for 1 year with a long-pulsed 1064 nm Nd:YAG laser (Cutera, Brisbane, Calif.) in contact mode. Thirty-eight patients had hypertrophic scars and 64 had keloids. The scars were evaluated before the treatment commenced and 1 month after the last session by using the Japan Scar Workshop Scar Scale 2011. Recurrence was assessed at 6 months after the termination of treatment. RESULTS: The average total Japan Scar Workshop score of the keloid and hypertrophic scar region groups dropped significantly after 1 year of treatment compared with before treatment (all P < 0.05). None of the hypertrophic scars or keloids deteriorated. However, 3 of the 34 anterior chest keloids (8.8%) did not respond. The following recurrence rates were observed 6 months after stopping laser treatment: 1 of the abdomen hypertrophic scars (4%), 18 of the anterior chest keloids (52.9%), 5 of the upper arm keloids (35.7%), and 4 of the scapula keloids (25%). CONCLUSIONS: Hypertrophic scars responded significantly better to 1064 nm Nd:YAG laser treatment than keloids. However, keloid recurrence occurred when there was remaining redness and induration, even if only a small part of the scar was affected.

DOI： 10.1097/GOX.0000000000000231

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Keloids are defined as overgrowths of scar tissue resulting from abnormal wound healing. They are characterized by excessive dermal deposition of thick, hyalinized collagen bundles resulting from an imbalance between the production and degradation of extracellular matrix (ECM) components. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are two important regulators of ECM degradation and remodeling. To evaluate the role played by knockdown of TIMPs in keloid formation, we transduced human keloid-derived fibroblasts (KFs) with small interfering RNAs targeting TIMP-1 or -2 (siTIMP-1 or siTIMP-2) using a lentiviral vector and assessed the biological effects. We found that MMP-1/TIMP-1 and MMP-1/TIMP-2 complexes were suppressed and that MMP-2 activity was upregulated in KFs expressing siTIMP-1 or siTIMP-2. In addition, increased degradation of collagen type I was observed in the supernatant of KFs expressing siTIMP-1, but not siTIMP-2, with the suppression of cell viability and induction of apoptosis. These results suggest that targeting TIMP-1 using small interfering RNA has significant therapeutic potential as an approach to treating keloids through degradation of their thick collagen bundles.

DOI： 10.1038/jid.2013.396

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

BACKGROUND: Treatments for earlobe keloids include surgical excision, postoperative radiotherapy, steroid injection, taping stabilization, and pressure therapy. However, to date, there is no universally accepted treatment strategy for earlobe keloid therapy. METHODS: A total of 174 lesions in 145 patients who attended the keloid/scar specialist clinic at the Department of Plastic, Reconstructive, and Aesthetic Surgery, Nippon Medical School, between 2006 and 2011 were included and were classified as having primary keloids or recurring keloids. Mild scars, such as hypertrophic scars, were excluded from this study. Appropriate surgical approaches, postoperative adjuvant therapies, such as radiotherapy, and postsurgical self-management were applied. The postsurgical radiotherapy modalities were 15 Gy administered in three fractions over 3 days and 10 Gy administered in two fractions over 2 days. Recurrence during the following 18-month follow-up period was recorded. RESULTS: Of the 174 lesions, 85.6 percent were primary keloids and 14.4 percent were recurrent keloids. Their recurrence rates were 4.7 percent and 0 percent, respectively. The overall recurrence rate was 4.0 percent. Complications during the 18-month follow-up period were not observed. The groups treated with 15-Gy and 10-Gy postsurgical radiotherapy did not differ significantly in terms of recurrence rate (p>0.05). CONCLUSIONS: Earlobe keloids can be treated by customized plans that involve appropriate surgical modalities, postoperative radiotherapy, and self-management. Postsurgical radiotherapy with 10 Gy of radiotherapy administered in two fractions over 2 days can be used successfully to treat earlobe keloids. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

DOI： 10.1097/PRS.0b013e3182a4c35e

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Pathological cutaneous scars such as keloids and hypertrophic scars (HSs) are characterized by a diffuse redness that is caused by the overgrowth of capillary vessels due to chronic inflammation. Our group has been using long-pulsed, 1064-nm Nd:YAG laser in noncontact mode with low fluence and a submillisecond pulse duration to treat keloids and hypertrophic scars since 2006 with satisfactory results. The present study examined the efficacy of this approach in 22 Japanese patients with keloids (n = 16) or hypertrophic scars (n = 6) who were treated every 3 to 4 weeks. Treatment settings were as follows: 5 mm spot size diameter; 14 J/cm(2) energy density; 300 μs exposure time per pulse; and 10 Hz repetition rate. The responses of the pathological scars to the treatment were assessed by measuring their erythema, hypertrophy, hardness, itching, and pain or tenderness. Moreover, skin samples from 3 volunteer patients were subjected to histological evaluation and 5 patients underwent thermography during therapy. The average total scar assessment score dropped from 9.86 to 6.34. Hematoxylin and eosin staining and Elastica Masson-Goldner staining showed that laser treatment structurally changed the tissue collagen. This influence reached a depth of 0.5 to 1 mm. Electron microscopy revealed plasma protein leakage, proteoglycan particles, and a change in the collagen fiber fascicles. Further analyses revealed that noncontact mode Nd:YAG laser treatment is highly effective for keloids and hypertrophic scars regardless of patient age, the origin and multiplicity of scarring, the location of the scar(s), or the tension on the scar.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

A study was conducted to evaluate the early results of high-dose-rate superficial brachytherapy (HDR-SB) after keloidectomy. Between April 2008 and April 2009, 21 patients with 36 histologically confirmed keloids were treated with postoperative HDR-SB. The tube applicator was placed on the skin to match the area of the surgical wound, and a spacer 5 mm thick was placed between the skin and the applicator. A dose evaluation point was established below 2 mm from skin surface, and 20 Gy was delivered in 4 daily fractions to keloidectomy scars on the anterior chest wall, scapular region, lower jaw and suprapubic region. A dose of 15 Gy was delivered in 3 daily fractions to lesions in other areas. The median follow-up period was 18 months (range, 9 to 29 months). Therapeutic outcome was judged in terms of recurrence, control, or acute side effects. Three keloids (9.7%) in two patients showed local recurrence, with a median time to failure after HDR-SB of 12 months. All recurrences affected the anterior chest wall. Dysraphia occurred in only one patient with an anterior chest wall lesion. Excluding the cases of recurrence, acceptable cosmetic results were achieved. Our results indicate that HDR-SB is effective and safe for preventing recurrence of keloids.

DOI： 10.1269/jrr.10159

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We use evidence-based algorithms to treat abnormal scarring, including keloids and hypertrophic scars (HSs). This involves a multimodal approach that employs traditional methods such as surgical removal, postoperative radiotherapy, corticosteroid injection, laser, and silicone gel sheets. As a result, the rate of abnormal scarring recurrence has decreased dramatically over the past 10 years. However, several problems remain to be solved. First, despite the optimization of a radiotherapy protocol, over 10% of cases who are treated with surgery and postoperative radiotherapy still recur in our facility. Second, the treatment options for cases with huge keloids are very limited. To address these problems, we performed basic research on the mechanisms that drive the formation of keloids and HSs. Extrapolation of these research observations to the clinic has led to the development of two treatment strategies that have reduced the rate of abnormal scar recurrence further and provided a means to remove large scars. Our finite element analysis of the mechanical force distribution around keloids revealed high skin tension at the keloid edges and lower tension in the keloid center. Moreover, when a sophisticated servo-controlled device was used to stretch wounded murine dorsal skin, it was observed that the stretched samples exhibited upregulated epidermal proliferation and angiogenesis, which are also observed in keloids and HSs. Real-time RT-PCR also revealed that growth factors and neuropeptides are more strongly expressed in cyclically stretched skin than in statically stretched skin. These findings support the well-established notion that mechanical forces on the skin strongly influence the cellular behavior that leads to scarring. These observations led us to focus on the importance of reducing skin tension when keloids/HSs are surgically removed to prevent their recurrence. Clinical trials revealed that subcutaneous/fascial tensile reduction sutures, which apply minimal tension on the dermis, are more effective in reducing recurrence than the three-layered sutures used by plastic surgeons. Moreover, we have found that by using skin flaps (e.g., perforator flaps and propeller flaps), which release tension on the wound, in combination with postoperative radiotherapy, huge keloids can be successfully treated.

DOI： 10.1272/jnms.78.68

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記述言語：日本語   出版者・発行元：(一社)日本創傷治癒学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：(株)全日本病院出版会  

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記述言語：日本語   出版者・発行元：(株)医学出版  

ケロイドは、ニキビなどの真皮網状層まで達する強い炎症をきっかけに高張力部位に主に発生し、できた硬いケロイド塊が、張力がかかる方向に向かって拡大・増悪していく。大きくなった硬いケロイド塊は力学的悪循環を繰り返していくが、適切な手術加療および術後放射線治療は、この力学的悪循環をリセットする意味でも効用は大きい。筆者らは、疼痛・そう痒の症状が強く醜状が問題となる場合や、瘢痕拘縮で機能障害がある場合、その他、表皮嚢腫を合併する場合や感染を繰り返す潰瘍を有する場合などでは、手術・術後放射線加療を積極的に検討している。ケロイドの摘出・縫合法の工夫に加えて、術後放射線治療、そして後療法を行うことで、ケロイドを完治することができるようになっている。本稿では、ケロイドの手術加療のコンセプトや工夫、術後放射線治療、そして後療法について、概要を解説していく。(著者抄録)

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記述言語：日本語   出版者・発行元：(株)全日本病院出版会  

ケロイドは、病理組織学的にはKeloidal collagen(KC)といわれる特徴的なコラーゲン線維が出現することが知られており、今回、KCがどこから産生されるかに焦点をあて、臨床診断でケロイドと診断された患者より採取した検体を対象に、電子顕微鏡による組織学的評価を行った。その結果、ケロイド組織内の細胞はαーSMA陽性を示し、筋線維芽細胞の組織学的特徴を有していた。さらに、組織学的に線維芽細胞様と血管内皮細胞様の2種類の筋線維芽細胞が認められ、筋線維芽細胞がこれらの細胞から分化した可能性が示唆された。従来、KC細胞は線維芽細胞が産生したコラーゲン線維が硝子変性(ヒアリン化)したものと考えられてきたが、上記の結果から、KCは筋線維芽細胞により産生され、発生時点ですでにKCとしての特徴を有している可能性が示唆された。

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記述言語：日本語   出版者・発行元：(株)全日本病院出版会  

ケロイド・肥厚性瘢痕と子宮筋腫の関連を明らかにすることを目的に、子宮筋腫の既往のある患者へアンケート調査を行い、121名より有効回答を得た。その結果、子宮筋腫摘出を目的とした開腹手術後の異常瘢痕発生率は62.0%で、先行研究による産婦人科での下腹部開腹手術後の異常瘢痕発生率(27%)より著明に高いことが分かった。

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記述言語：日本語   出版者・発行元：(株)全日本病院出版会  

婦人科手術後に発生する肥厚性瘢痕およびケロイドの予防と早期治療を目的に当科(大学附属病院形成外科)では、2006年に産婦人科手術後患者を対象としたScar Control外来を立ち上げ、これまで1万人を超える症例の術後瘢痕経過を診察し、下腹部術後肥厚性瘢痕およびケロイドの発生について検討してきた。今回、2006〜2016年までに当院産婦人科にて手術治療を受けた症例1000例(縦瘢痕500例、横瘢痕500例)を対象に、術後下腹部瘢痕の1ヵ月後タイプ分類、下腹部術後肥厚性瘢痕およびケロイドの発生率(術後1年)、早期治療(ステロイド含有テープ治療)介入による下腹部術後肥厚性瘢痕およびケロイド抑制効果などについて検討した。その結果、下腹部術後肥厚性瘢痕およびケロイドの術後1年目の発生率は、縦瘢痕(500例)で27%、横瘢痕(500例)で24%であった。また、縦瘢痕については、術後1ヵ月時に6タイプの瘢痕に分類が可能で、それぞれのタイプにより術後1年目の瘢痕結果が異なっていたが、瘢痕タイプがA(評価項目である「赤み」「硬さ」「盛り上がり」のいずれも「なし」)以外の患者に術後1ヵ月目から保存的治療による早期治療介入を行うと、術後1年目の肥厚性瘢痕およびケロイドの発生率は低下した。

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

82歳。ペットボトルによる自慰後に陰茎がペットボトルの口から抜けなくなり、発熱、陰茎腫脹をきたした。前医にて陰茎絞扼症による尿閉の診断で膀胱瘻造設が行われた。陰茎根部から腹壁にかかる皮膚壊死、尿道損傷、敗血症の合併を認め、緊急陰茎全摘術後に複数回のデブリードマン、残存尿道摘除、抗生剤投与を行った。初診より12ヵ月経過現在、経過良好である。

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J04260&link_issn=&doc_id=20210301380004&doc_link_id=%2Fcw1nimed%2F2021%2F001701%2F005%2F0021-0024%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcw1nimed%2F2021%2F001701%2F005%2F0021-0024%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

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記述言語：日本語   出版者・発行元：克誠堂出版(株)  

当院では耳ケロイドに対し基本的に外科的切除+術後放射線治療の組み合わせを第一選択としており、外来受診、手術、放射線治療(1〜2日)、抜糸の最低4〜5日間の通院で治療が可能である。外科的切除では耳垂には楔状切除、耳介にはくり抜き法を基本とし、症例に応じてZ形成術や皮弁作成術を追加しており、術後はケロイドの再発予防を目的として十分な圧迫固定を行い、基本的には術後3日以内に放射線治療を開始している。また、術後は1〜1ヵ月半毎に6ヵ月〜数年間の経過観察を行い、術後創部の硬さを認める症例には早期よりステロイド治療を開始している。現時点で再発率の上昇はなく、放射線治療に伴う有害事象も認めていない。

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記述言語：日本語   出版者・発行元：克誠堂出版(株)  

当院では耳ケロイドに対し基本的に外科的切除+術後放射線治療の組み合わせを第一選択としており、外来受診、手術、放射線治療(1〜2日)、抜糸の最低4〜5日間の通院で治療が可能である。外科的切除では耳垂には楔状切除、耳介にはくり抜き法を基本とし、症例に応じてZ形成術や皮弁作成術を追加しており、術後はケロイドの再発予防を目的として十分な圧迫固定を行い、基本的には術後3日以内に放射線治療を開始している。また、術後は1〜1ヵ月半毎に6ヵ月〜数年間の経過観察を行い、術後創部の硬さを認める症例には早期よりステロイド治療を開始している。現時点で再発率の上昇はなく、放射線治療に伴う有害事象も認めていない。

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記述言語：日本語   出版者・発行元：医学図書出版(株)  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

DOI： 10.1272/manms.15.226

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：(株)全日本病院出版会  

姿勢変換に伴う皮膚の伸展変化率やその特徴、持続時間などをケロイドの好発部位との関係性において検討した。ヒトの基本3姿勢(座位、立位、臥位)に着目し、健常者10人の姿勢変化による皮膚の伸展の変化をケロイドの好発部位(前胸部、肩甲部、後肩部、下顎部)、低発生部位(上腕部、大腿外側)、無発生部位(前脛骨部、前額部)の3群に分けて調査した。ケロイド好発部位は体位変換によって、およそ20〜30%にも上る伸展刺激が加わっていることが判明した。また、低発生部位には10%程度の伸展刺激が加わっており、無発生部位に関してはおよそ5%にも満たない程度の伸展刺激しか加わっていないことが判明した。ケロイド好発部位においては、およそ20〜30%の最大の伸展変化を起こした姿勢変化の際、2関節以上の影響を受けて直交する2軸で正負の一致した強い伸展変化が起こっていることが示唆された。

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記述言語：日本語   出版者・発行元：(一社)日本創傷治癒学会  

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記述言語：日本語   出版者・発行元：(一社)日本創傷治癒学会  

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記述言語：日本語   出版者・発行元：(一社)日本創傷治癒学会  

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記述言語：日本語   出版者・発行元：(一社)日本創傷治癒学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：(株)全日本病院出版会  

瘢痕の発赤の原因である過剰増生している血管を標的として1064nmのロングパルスNd:YAGレーザーの接触照射の効果と適応について検討した。Nd:YAGレーザーの接触照射のみを施行し、12ヵ月以上経過観察できた30例を対象とした。各部位別(18点満点)では、施術前後の平均点の変化が、顔面6.3→0.7、頸部4.0→1.0、前胸部8.5→4.7、上肢5.0→3.1、下腹部7.0→3.7、下肢4.0→3.0であった。各項目毎(3点満点)では硬結1.77→0.8、隆起1.9→1.0、発赤2.0→1.O3、周囲発赤浸潤0.87→0.5、自発痛・圧痛0.4→0.13、そう痒0.4→0.13であった。Nd:YAG治療を開始した患者においては、Nd:YAGレーザーの効果が期待できると判断した患者を施術者が選択しているものの、概ね良好な結果を得ることができた。

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：(株)全日本病院出版会  

ケロイド・肥厚性瘢痕に対して手術治療を選択した場合、術後再発予防目的の瘢痕ケアにシリコーンジェルシートやサージカルテープが広く用いられているが、サージカルテープは皮膚の糜爛を生じることがある。著者らは、メンリッケヘルス社製のソフトシリコーンテープ「メピタック」を用いており、良好な結果が得られているので報告した。メピタックは固定が強固でありながらテープ交換時の疼痛・皮膚損傷が少なく、皮膚が脆弱・敏感な患者や、テープを同じ部位に継続して使用する場合に適していた。代表例として、サージカルテープで皮膚糜爛を生じたためメピタックに変更した1例を提示した。

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記述言語：日本語   出版者・発行元：(株)全日本病院出版会  

ケロイドに対する術後照射には電子線が多用されてきたが、長く平坦でない術創には均一な線量分布を得ることが困難であった。また、外部照射の代替法として組織内照射があるが、この方法は、アプリケータの留置期間を短縮するために非常に過密な照射スケジュールを要し、医療スタッフと患者の双方に時間的・身体的ストレスを負わせる。そこで著者らは高線量率小線源治療装置による表在照射(以下SBT)を2008年4月から開始した。今回、その方法を紹介し、2009年4月までに施行した21例36部位の成績を報告した。照射部位の内訳は、胸壁16、肩甲部7、下顎6、恥骨部4、その他3であり、成績は、経過観察期間中(9〜29ヵ月)に再発を3部位(8.3%)に認めたが、再発例を除く患者の美容的満足度は高かった。この成績は、以前報告した電子線の成績とほぼ同等であるが、SBTでは電子線と異なり、平坦でない術創でも均一な線量を投与できるため、照射部位の形態が下顎など曲面の症例で再発がないという特長が認められた。

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記述言語：日本語   出版者・発行元：(株)全日本病院出版会  

前胸部の巨大なケロイドに対し皮弁手術目的でMDCTによる皮膚穿通枝造影検査を施行した9例の画像をもとに、ケロイドと周囲皮膚における「動静脈分布」「内胸動静脈穿通枝分布」「血管構造」の解析を行った。その結果、ケロイド中心部は血行不良であるのに対し、ケロイド表面から周囲にかけては著明な血管新生と血流量増加が認められ、これはケロイド本体の虚血に伴う代償性変化、またはケロイド自体の炎症に伴う炎症性変化ではないかと推測された。内胸動静脈穿通枝の分布については、ケロイド周囲に位置する穿通枝が他部位の穿通枝に比べて有意に拡張していた。

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記述言語：日本語   出版者・発行元：(一社)日本創傷外科学会  

肥厚性瘢痕やケロイドは創傷治癒過程での異常が原因で生じる皮膚の線維増殖性疾患であり,慢性的に持続する炎症が特徴的である。文献的考察から,ケロイド・肥厚性瘢痕の局所的因子として,(1)創にかかる周期的な皮膚張力,(2)不適切な湿潤環境,(3)異物反応,アレルギー反応,(4)感染の反復に加え,その後の「炎症の持続」があると考えられた。特に(1)〜(4)の原因となる「物理的刺激の軽減」と対症療法としての「炎症の軽減」に重点を置くことにより,現在の治療がどのような目的で行われているか医師も患者も理解しやすくなり,治療が円滑に進むと考えられた。また,われわれが行っている物理的刺激の軽減に関与する治療法として,1.減張縫合の改善,2.Z形成術,3.Small Wave Incision,4.くり抜き法,5.皮弁による再建,6.ジェルシートやテープによる創の固定,また炎症の軽減に関与する治療法として,1.術後放射線療法,2.ケロイドに対する放射線単独治療,3.レーザー治療,4.副腎皮質ホルモン剤の工夫,について考察した。(著者抄録)

DOI： 10.11310/jsswc.3.82

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記述言語：日本語   出版者・発行元：(株)全日本病院出版会  

耳ケロイドは、発生部位が耳介軟骨部か耳垂部かによって治療後の再発率が異なることが示されている。そこで著者等は、それぞれの部位に適した治療法を確立するために検討を行ってきた。2002年以前の治療方法は両部位ともケロイドの単純切除術+一期的縫縮術と術後15Gy/3分割/3日間の電子線照射を行っており、耳垂部ケロイドの再発率は5.7%(2/35例)と概ね良好であったが、耳介軟骨部ケロイドの再発率は38.5%(5/13例)と高かった。このため2003年から治療方法を変更した。具体的には、耳介軟骨部のケロイドに対しては、皮膚に生じた張力を減弱させる目的で、腫瘤は全てを切除するのではなく、内部の瘢痕組織を主に切除して皮膚を残す「くり抜き法」を施行するようにした。術後の電子線照射は従来どおり15Gy/3分割/3日間とし、再発率は10%(2/20例)に低下した。耳垂部のケロイドに対しては、単純切除術と6-0 Prolineによる縫合を行った後10Gy/2分割/2日間の電子線照射を行うようにし、再発率は6.7%(8/120例)となった。

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記述言語：日本語   出版者・発行元：(株)全日本病院出版会  

著者等はケロイド・肥厚性瘢痕に対し、プローベを病変部から2〜3cm離して照射を行う非接触ロングパルスNd:YAGレーザー照射を施行している。すなわち、1064nm Nd:YAGレーザー(キュテラ社製)の非接触モードで治療を行っている。今回、本法を施行したケロイド16例と肥厚性瘢痕6例の成績を報告した。照射条件は5mmスポットでエネルギーを14J/cm2に設定し、1例あたり平均14セッションの治療を行った。治療成績の評価方法は、「紅斑」「肥厚」「硬結」「そう痒」「疼痛」の5項目についてそれぞれ0〜3点の4段階評価を行い、その合計点を治療前後で比較し。結果、治療前の平均点は9.86点で、治療後は6.34に低下(改善)した。本レーザーの有用性を色素レーザーと比較するためハーフサイドテストを行い、照射部の組織学的差異について検討した結果、本レーザーの非接触照射を行った瘢痕の血管に変化は認めなかったのに対し、色素レーザー照射を行った瘢痕には血管の有意な減少を認めた。

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記述言語：日本語   出版者・発行元：(株)全日本病院出版会  

著者等は巨大なケロイドに対して皮弁を用いた再建術を行っており、特に、血管茎を軸に回転させて移動するプロペラ皮弁を好んで用いてきた。今回、切除後一期的縫縮が不可能なケロイドに対してプロペラ皮弁を使用し術後1年以上経過観察しえた13例の成績を報告した。手術部位は胸部が10例、肩が1例、恥骨上部が2例で、皮弁は部位別にそれぞれ内胸動脈穿通枝茎プロペラ皮弁、胸背動静脈茎プロペラ皮弁、浅腸骨回旋動静脈プロペラ皮弁を使用した。皮弁の挙上方法は、血管茎を同定した後、少なくとも浅筋膜を含むように挙上し、皮弁内の浅筋膜や深筋膜を移植床の筋膜と縫合することで皮弁の皮膚にかかる張力を軽減させる工夫を行った。皮弁採取部位に対しては、筋膜レベルで確実に減張縫合を行い、真皮縫合は最小限とした。術後は20Gy/4分割/4日間の密封小線源による高線量率表在照射を皮弁採取部と移植床縫合部双方に行い、抜糸後はサージカルテープによるテーピング固定を行った。手術成績は全例で皮弁の完全生着が得られ、ケロイドの再発は1例も認めていない。

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記述言語：日本語   出版者・発行元：(一社)日本頭蓋顎顔面外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本熱傷学会  

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記述言語：日本語   出版者・発行元：(NPO)日本レーザー医学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：(一社)日本褥瘡学会  

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記述言語：日本語   出版者・発行元：(株)全日本病院出版会  

くり抜き法の手術手技について解説し、本法を施行した12例の成績を報告した。12例の術後観察期間は12〜21ヵ月で、再発したものは1例もなかった。一般に耳介の手術は再発率が高いといわれているが、くり抜き法は整容的に優れているだけでなく再発率も低いことが示された。巨大なケロイドほどその有用性は高く、治療に難渋する症例に対して推奨される方法と考えられた。

CiNii Research

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記述言語：日本語   出版者・発行元：(一社)日本頭蓋顎顔面外科学会  

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記述言語：日本語   出版者・発行元：日本外科系連合学会  

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記述言語：日本語  

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記述言語：日本語  

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記述言語：日本語   出版者・発行元：(一社)日本熱傷学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本頭蓋顎顔面外科学会  

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記述言語：日本語   出版者・発行元：(株)全日本病院出版会  

肥厚性瘢痕治療やケロイドの症状軽減に汎用されるシリコンジェルシート(SGS)の減張効果について有限要素法(FEM)を用いて検討した。その結果、SGSの厚さが正常皮膚と同じで硬さ半分としたモデルでは瘢痕両端の応力(張力)が最高値を示し、高応力部位は瘢痕と正常組織の境界から正常組織に広がるように認められた。しかし、SGSをのせたモデルでは瘢痕両端の応力は低下し、SGS辺縁の正常皮膚に起こる応力変化の上昇を認めた。SGSの硬さでは柔らかいほど瘢痕周囲応力変化の低減を認めず、硬さが正常皮膚とほぼ等しくなると瘢痕周囲応力変化は変わらないことが判明した。SGSの厚さでは正常皮膚の半分以下では瘢痕周囲応力の低減効果が減弱し、SGSが厚くなるのに比例しSGS辺縁の正常皮膚の応力変化は上昇した。以上より、SGSの効果は瘢痕の安静・減張であることがシミュレーションで示唆され、力学的に理想的なSGSの硬さは正常皮膚に近く、厚さは正常皮膚の0.5〜1.0倍と考えられた。

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記述言語：日本語   出版者・発行元：(一社)日本美容外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本熱傷学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：日本シミュレーション外科学会  

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記述言語：日本語   出版者・発行元：日本外科系連合学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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