Comparison of leg volume ratio between inguinal lymphadenectomy and inguino-pelvic lymphadenectomy in patients with skin cancer of the lower extremity
Taku Maeda, Kosuke Ishikawa, Toshihiko Hayashi, Hiroshi Furukawa, Takahiro Miura, Masahiro Hojo, Emi Funayama, Yuhei Yamamoto
Journal of Plastic, Reconstructive & Aesthetic Surgery, 99, 397, 405, Elsevier BV, 2024年12月
研究論文（学術雑誌）

Physiological and Functional Restoration of the Modiolus Using a Double Tendon Sling in Patients With Full-Thickness Oral Defects
Taku Maeda, Toshihiko Hayashi, Kosuke Ishikawa, Takahiro Miura, Emi Funayama, Yuhei Yamamoto
Annals of Plastic Surgery, Ovid Technologies (Wolters Kluwer Health), 2024年10月18日
研究論文（学術雑誌）, Background

Reconstruction of the oral modiolus should be considered for facial defects involving the lip and cheek. We have performed free flap reconstruction using a novel technique that includes a vertical and a horizontal sling for full-thickness defects involving the oral commissure.

Patients and Methods

We used a free radial forearm flap and the palmaris longus tendon to correct lip and cheek defects in 6 patients (3 men, 3 women; age, 55–84 years). The tendon was divided into 2 portions for use as the double sling. One sling was used to connect the upper and lower stumps of the orbicularis oris in the vertical direction and the other to connect the vertical sling and masseter muscle. The outcomes assessed were esthetic appearance and functional results.

Results

The facial defects ranged in size from 3.0 cm × 4.0 cm to 7.0 cm × 6.0 cm and the mucosal defects from 1.5 cm × 4.0 cm to 6.5 cm × 5.0 cm. The length of the harvested tendon ranged from 11.5 to 13.5 cm. All flaps survived without complications. Good esthetic outcomes were achieved (excellent facial appearance, n = 1; no lip deviation or drooping, n = 5). Functionally, all patients had acceptable mouth opening and were able to eat a regular diet.

Conclusions

Good physiological and functional results can be achieved using a double tendon sling for reconstruction of the modiolus in patients with full-thickness defects involving the oral commissure.

Hypoxic culture enhances the antimicrobial activity of amnion-derived mesenchymal stem cells, thereby reducing bacterial load and promoting wound healing in diabetic mice
Riku Ishii, Shunsuke Ohnishi, Masahiro Hojo, Kosuke Ishikawa, Emi Funayama, Takahiro Miura, Naoto Okubo, Kazufumi Okada, Yuhei Yamamoto, Taku Maeda
Biochemical and Biophysical Research Communications, 150903, 150903, Elsevier BV, 2024年10月
研究論文（学術雑誌）

Distinct Roles of Omental and Latissimus Dorsi Flaps for Blocking Infection Pathways and Protecting A Left Ventricular Assist Device
Dongkyung Seo, Taku Maeda, Tomonori Ooka, Takahiro Miura, Kosuke Ishikawa, Emi Funayama, Satoru Wakasa, Yuhei Yamamoto
The Heart Surgery Forum, 27, 9, E998, E1002, Forum Multimedia Publishing LLC, 2024年09月10日
研究論文（学術雑誌）, Left ventricular assist devices (LVADs) are vital for managing severe heart failure in transplant-ineligible patients, but device exposure and infection pose significant challenges. This report details a 42-year-old man with dilated cardiomyopathy and bronchial asthma who presented with an externalized LVAD following a HeartMate II to HeartMate III exchange due to malfunction. Our tailored surgical strategy treated the LVAD driveline and main body as two distinct parts. This distinction is crucial, as major upstream infections typically originate from the driveline. We applied flaps to these parts for different purposes, maximizing their unique characteristics. The omental flap, chosen for its flexibility, blood supply, and immunological activation upon foreign body contact, covered the driveline. The latissimus dorsi flap provided vascularity and mechanical protection for the LVAD. Additionally, we review the omentum's basic physiological aspects, which are often unfamiliar to clinicians. Infection has not recurred in 6 months postoperatively, demonstrating the approach's effectiveness.

Leukocytoclastic Vasculitis-Induced Lower Leg Ulceration in the Course of Immune Checkpoint Inhibitor Therapy for Advanced Malignant Melanoma: A Case Report
Dongkyung Seo, Shin Ariga, Kosuke Ishikawa, Takahiro Miura, Rika Moku, Emi Funayama, Yuhei Yamamoto, Taku Maeda
Journal of Wound Management and Research, 20, 2, 168, 172, Korean Wound Management Society, 2024年06月30日
研究論文（学術雑誌）, Immune checkpoint inhibitors (ICIs) have expanded therapeutic options for advanced malignancies, offering new hope for conditions once deemed untreatable. However, the advent of ICIs has introduced a spectrum of immune-related adverse events (irAEs), including leukocytoclastic vasculitis (LCV), a rare but significant complication. This case report describes development of LCV after treatment with nivolumab and ipilimumab in a 70-year-old man with malignant melanoma, highlighting the diagnostic and management challenges of such irAEs. Despite extensive investigation, conventional pathology failed to identify the immune complexes typically associated with LCV. The clinical presentation, alongside a detailed medical history and the exclusion of infections, medications, and autoimmune diseases, was crucial in establishing a diagnosis. Ulcer resolution following discontinuation of ICI therapy and initiation of steroids further support the conclusion that LCV was an irAE in this patient. This case underscores the need for vigilant monitoring for irAEs for the variable onset after ICI therapy and the importance of thorough history-taking to guide diagnosis and treatment. With ICIs becoming increasingly prevalent in oncology, the incidence of ICI-induced ulcers like LCV is expected to rise, necessitating heightened awareness and multidisciplinary approaches to patient care.

Fluoroscopy- and endoscopy-guided transoral sclerotherapy using foamed polidocanol for oropharyngolaryngeal venous malformations in a hybrid operation room: A case series
Ishikawa K, Maeda T, Funayama E, Murao N, Miura T, Sasaki Y, Seo D, Mitamura S, Oide S, Yamamoto Y, Sasaki S
Journal of Clinical Medicine, 13, 8, 2369, 2024年04月18日, ［査読有り］, ［招待有り］
英語, 研究論文（学術雑誌）

Lymphatic drainage patterns of malignant skin tumors in the head and neck region: a single-center retrospective study
Nishio T, Maeda T, Ishikawa K, Murao N, Fuyama K, Yamamoto Y, Hayashi T
International Journal of Clinical Oncology, 2024年03月30日, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）

Refinement of Surgery for Postaxial Polysyndactyly of the Toes
Kosuke Ishikawa, Hiroshi Furukawa, Yuhei Yamamoto, Emi Funayama, Takahiro Miura, Taku Maeda
Annals of Plastic Surgery, Ovid Technologies (Wolters Kluwer Health), 2024年03月27日
研究論文（学術雑誌）, Purpose

Treatment for polysyndactyly of the toes aims at cosmetic improvement but the lateroplantar rotation of the new fifth toe remains challenging. This study evaluated our novel surgical procedure for postaxial polysyndactyly of the toes.

Materials and Methods

Patients with postaxial polysyndactyly involving the fourth, fifth, and sixth toes treated in 2007 to 2017 with a minimum follow-up duration of 1 year were retrospectively investigated. Our aims of surgery for this condition were to avoid excessive lateroplantar rotation of the new fifth toe by using a proximally elongated plantar “shark-fin flap” and to make the tip of this toe appear to be naturally pointing inward by using the dog-ear component of the flap on the tip of the toe. The excess skin of the shark-fin flap was grafted onto the lateral surface of the fourth toe. Lateroplantar rotation of the fifth toe in these patients was compared with that in photographs of the feet of 96 normal 4-year-old children.

Results

A total of 11 feet in 10 patients (6 male, 4 female; mean age 1.3 years) were analyzed. Syndactyly between the fourth and fifth toes was complete in 3 feet, incomplete at the level of the distal interphalangeal joint of the fifth toe in 5, and incomplete at the level of the proximal interphalangeal joint of the fifth toe in 3. Lateroplantar rotation of the fifth toe, evaluated by the mean angle between 2 intersecting lines extending from the proximal nail fold of the third and fifth toes, was 25 ± 10° in normal feet and 0 ± 12° in operated feet with polysyndactyly. The absolute left-right difference in this angle was 7 ± 5° in normal children and 22 ± 12° in patients with polysyndactyly. Valgus deformity of the new fifth toe improved in all patients during a mean postoperative follow-up of 3.8 years.

Conclusions

Using our procedure, no excessive lateroplantar rotation has been observed when the tip of the fifth toe is inclined inward using a dog-ear flap component. This procedure could be useful in patients in whom the cosmetic outcome is a priority.

Negative Pressure Wound Therapy with Instillation and Dwell Time in Patients on Hemodialysis
Erika Guilpain Kusajima, Kosuke Ishikawa, Emi Funayama, Takahiro Miura, Katsumi Horiuchi, Suguru Matsui, Tatsuya Saito, Hotaka Matsui, Yuhei Yamamoto, Taku Maeda
International Journal of Surgical Wound Care, 5, 1, 1, 7, Japan Society for Surgical Wound Care, 2024年03月01日
研究論文（学術雑誌）

Intranodal lymphangiography with lipiodol as a diagnostic and therapeutic approach for spontaneous cervical chyle leak
Sasaki Y, Sakuhara Y, Sasaki S, Maeda T, Yamamoto Y, Ishikawa K
Clinical Case Reports, 11, 12, e8161, 2023年12月19日, ［査読有り］
英語, 研究論文（学術雑誌）

Burn conversion possibly caused by COVID-19 infection: A case report
Dongkyung Seo, Taku Maeda, Yuhei Yamamoto, Emi Funayama, Takahiro Miura, Norifumi Matsuda, Kosuke Ishikawa
Burns Open, Elsevier BV, 2023年12月
研究論文（学術雑誌）

Partially involuting congenital hemangioma with pyogenic granuloma‐induced rapid progression following incisional biopsy in infancy: A case report
Yuki Sasaki, Kosuke Ishikawa, Takahiro Miura, Emi Funayama, Yuhei Yamamoto, Taku Maeda
Clinical Case Reports, 11, 10, Wiley, 2023年10月17日
研究論文（学術雑誌）, Key Clinical Message

We present a case of partially involuting congenital hemangioma (PICH) that showed rapid growth with ulceration after incisional biopsy. PICH does not typically grow after birth. However, if growth occurs due to stimuli like biopsy, it is essential to consider the possibility of pyogenic granuloma complication.

Targeted next-generation sequencing for detection of PIK3CA mutations in archival tissues from patients with Klippel–Trenaunay syndrome in an Asian population
Yuki Sasaki, Kosuke Ishikawa, Kanako C. Hatanaka, Yumiko Oyamada, Yusuke Sakuhara, Tadashi Shimizu, Tatsuro Saito, Naoki Murao, Tomohiro Onodera, Takahiro Miura, Taku Maeda, Emi Funayama, Yutaka Hatanaka, Yuhei Yamamoto, Satoru Sasaki
Orphanet Journal of Rare Diseases, 18, 1, Springer Science and Business Media LLC, 2023年09月04日
研究論文（学術雑誌）, Abstract

Background

Klippel–Trenaunay syndrome (KTS) is a rare slow-flow combined vascular malformation with limb hypertrophy. KTS is thought to lie on the PIK3CA-related overgrowth spectrum, but reports are limited. PIK3CA encodes p110α, a catalytic subunit of phosphatidylinositol 3-kinase (PI3K) that plays an essential role in the PI3K/AKT/mammalian target of rapamycin (mTOR) signaling pathway. We aimed to demonstrate the clinical utility of targeted next-generation sequencing (NGS) in identifying PIK3CA mosaicism in archival formalin-fixed paraffin-embedded (FFPE) tissues from patients with KTS.

Results

Participants were 9 female and 5 male patients with KTS diagnosed as capillaro-venous malformation (CVM) or capillaro-lymphatico-venous malformation (CLVM). Median age at resection was 14 years (range, 5–57 years). Median archival period before DNA extraction from FFPE tissues was 5.4 years (range, 3–7 years). NGS-based sequencing of PIK3CA achieved an amplicon mean coverage of 119,000x. PIK3CA missense mutations were found in 12 of 14 patients (85.7%; 6/8 CVM and 6/6 CLVM), with 8 patients showing the hotspot variants E542K, E545K, H1047R, and H1047L. The non-hotspot PIK3CA variants C420R, Q546K, and Q546R were identified in 4 patients. Overall, the mean variant allele frequency for identified PIK3CA variants was 6.9% (range, 1.6–17.4%). All patients with geographic capillary malformation, histopathological lymphatic malformation or macrodactyly of the foot had PIK3CA variants. No genotype–phenotype association between hotspot and non-hotspot PIK3CA variants was found. Histologically, the vessels and adipose tissues of the lesions showed phosphorylation of the proteins in the PI3K/AKT/mTOR signaling pathway, including p-AKT, p-mTOR, and p-4EBP1.

Conclusions

The PI3K/AKT/mTOR pathway in mesenchymal tissues was activated in patients with KTS. Amplicon-based targeted NGS could identify low-level mosaicism from low-input DNA extracted from FFPE tissues, potentially providing a diagnostic option for personalized medicine with inhibitors of the PI3K/AKT/mTOR signaling pathway.

Development of a simultaneous and noninvasive measuring method using high-frame rate videography and motion analysis software for the assessment of facial palsy recovery in a rat model
Takahiro Miura, Yuhei Yamamoto, Emi Funayama, Kosuke Ishikawa, Taku Maeda
Journal of Plastic, Reconstructive & Aesthetic Surgery, 82, 211, 218, Elsevier BV, 2023年07月
研究論文（学術雑誌）

Utility of Color Doppler Ultrasonography in Monitoring of a Free Jejunal Flap
Taku Maeda, Kosuke Ishikawa, Yoichiro Oda, Satoshi Kano, Nayuta Tsushima, Tomohiro Sakashita, Akihiro Homma, Yuhei Yamamoto, Emi Funayama
The Laryngoscope, Wiley, 2023年06月29日
研究論文（学術雑誌）

皮膚欠損用創傷被覆材Sorbactコンプレスを用いた広範囲熱傷デブリードマン後の局所療法　　　　　　　　　　　　　　　
石川 耕資, 北條 正洋, 星野 善允, 石井 浩子, 石井 陸, 佐々木 雄輝, 徐 東經, 松田 識郁, 三浦 隆洋, 前田 拓, 舟山 恵美, 山本 有平
熱傷, 49, 2, 103, 103, (一社)日本熱傷学会, 2023年06月
日本語

Therapeutic Potential of the Prolyl Hydroxylase Inhibitor Roxadustat in a Mouse Hindlimb Lymphedema Model
Yoshitada Hoshino, Masayuki Osawa, Emi Funayama, Kosuke Ishikawa, Takahiro Miura, Masahiro Hojo, Yuhei Yamamoto, Taku Maeda
Lymphatic Research and Biology, 21, 4, 372, 380, Mary Ann Liebert Inc, 2023年03月07日
研究論文（学術雑誌）

Effectiveness and safety of percutaneous sclerotherapy using absolute ethanol and/or polidocanol for maxillofacial venous malformations involving the masticatory muscles: A case series
Kosuke Ishikawa, Satoru Sasaki, Hiroshi Furukawa, Taku Maeda, Takahiro Miura, Yuki Sasaki, Yuhei Yamamoto, Emi Funayama
Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, 135, 3, 355, 362, Elsevier BV, 2023年03月
研究論文（学術雑誌）

Efficacy of hyperbaric oxygen after microtia reconstruction using costal cartilage: A retrospective case-control study
Naoki Murao, Akihiko Oyama, Yuhei Yamamoto, Emi Funayama, Kosuke Ishikawa, Taku Maeda
Undersea and Hyperbaric Medicine, Undersea and Hyperbaric Medical Society (UHMS), 2023年01月01日
研究論文（学術雑誌）, Introduction: Microtia reconstruction with autologous costal cartilage framework grafting is challenging because the three-dimensional structure of the ear is highly complex, and meeting the high aesthetic demands of patients can be difficult. If the skin flap overlying the framework is thinned to achieve a smooth and accentuated outline, a poor blood supply in the thin skin flap may lead to skin necrosis, exposure of the framework, and poor surgical results. Hyperbaric oxygen (HBO2) therapy can promote the healing of complex wounds and flaps. This study sought to determine the effectiveness of HBO2 therapy for prevention of postoperative complications after framework grafting in microtia reconstruction. Methods: We retrospectively evaluated postoperative complications and compared outcomes in pediatric patients who underwent costal cartilage grafting for microtia reconstruction at our institution between 2011 and 2015 according to whether or not they received postoperative HBO2 therapy. HBO2 therapy was applied once daily for a total of 10 sessions starting on the first postoperative day. Results: During the study period, eight patients received HBO2 therapy after costal cartilage grafting and 12 did not. There was no significant difference in the incidence of postoperative ulcers. However, the incidence of framework exposure was lower and the healing time was shorter in patients who received HBO2 therapy than in those who did not. Discussion: HBO2 therapy can be used safely in pediatric patients to reduce postoperative complications and improve the aesthetic outcome of microtia reconstruction. After costal cartilage grafting, HBO2 therapy should be considered as adjuvant therapy.

ProPlan CMFを用いた術前3Dシミュレーションに基づく下顎再建の経験　　　　　　　　　　　　　　　
北條 正洋, 前田 拓, 三浦 隆洋, 石川 耕資, 大澤 昌之, 舟山 恵美, 足利 雄一, 山本 有平
日本マイクロサージャリー学会学術集会プログラム・抄録集, 49回, 222, 222, (一社)日本マイクロサージャリー学会, 2022年12月
日本語

Sentinel node restoration by vascularized lymph node transfer in mice
Erika G. Kusajima, Yuhei Yamamoto, Kosuke Ishikawa, Takahiro Miura, Emi Funayama, Masayuki Osawa, Ryo Takagi, Taku Maeda
Microsurgery, Wiley, 2022年11月02日
研究論文（学術雑誌）

腓骨再建における術前3Dシミュレーションの活用　　　　　　　　　　　　　　　
石井 陸, 前田 拓, 三浦 隆洋, 石川 耕資, 舟山 恵美, 山本 有平
日本頭蓋顎顔面外科学会学術集会プログラム・抄録集, 40回, 136, 136, (一社)日本頭蓋顎顔面外科学会, 2022年11月
日本語

Restoration of lymph flow by flap transfer can prevent severe lower extremity lymphedema after inguino-pelvic lymphadenectomy
Taku Maeda, Yuhei Yamamoto, Toshihiko Hayashi, Hiroshi Furukawa, Kosuke Ishikawa, Takahiro Miura, Masahiro Hojo, Emi Funayama
Surgery Today, 53, 5, 588, 595, Springer Science and Business Media LLC, 2022年10月29日
研究論文（学術雑誌）

Streptococcal Toxic Shock Syndrome in a Pediatric Patient With Intramuscular Venous Malformation in the Neck
Norifumi Matsuda, Kosuke Ishikawa, Emi Funayama, Shintaro Mitamura, Satoru Sasaki, Yuhei Yamamoto, Taku Maeda
The Journal of Emergency Medicine, Elsevier BV, 2022年10月
研究論文（学術雑誌）

チームサージャリーにおける形成外科の貢献 新型コロナウイルス感染症が及ぼした影響　　　　　　　　　　　　　　　
松田 識郁, 石川 耕資, 前田 拓, 大澤 昌之, 舟山 恵美, 村尾 尚規, 林 利彦, 山本 有平
日本形成外科学会会誌, 42, 7, 369, 374, (一社)日本形成外科学会, 2022年07月
日本語, 序論/目的:形成外科において他科と共同で行うチームサージャリーは重要な分野であるが、その症例の多くは他科入院であるため、病院経営に対する形成外科の経済的貢献度は明らかになりにくい。チームサージャリーにおける形成外科の貢献度を明らかにすべく、他科共同手術の検討を行い、新型コロナウイルス感染症(以下、COVID-19)が及ぼした影響について考察した。方法:2017～2020年度の4年間に手術に協力した他科入院手術の検討を行った。結果:入院科はCOVID-19前では耳鼻咽喉科(31.4%)が最多であったが、COVID-19後では救急科(38.3%)が最多であった。COVID-19前後で形成外科入院総手術点数は減少したが、他科共同手術の形成外科手術点数は増加した。形成外科が関与した総手術点数は変化がなかった。結論:チームサージャリーにおける形成外科の貢献度とCOVID-19による影響が明らかにされた。幅広い領域において手術に協力することで、社会情勢や医療体制による影響を抑えられることが示された。(著者抄録)

好酸球性多発血管炎性肉芽腫症に伴う神経障害によって足部潰瘍を生じた1例　　　　　　　　　　　　　　　
石井 陸, 村尾 尚規, 石川 耕資, 舟山 恵美, 前田 拓, 大澤 昌之, 山本 有平
創傷, 13, 3, 124, 127, (一社)日本創傷外科学会, 2022年07月
日本語

チームサージャリーにおける形成外科の貢献 新型コロナウイルス感染症が及ぼした影響　　　　　　　　　　　　　　　
松田 識郁, 石川 耕資, 前田 拓, 大澤 昌之, 舟山 恵美, 村尾 尚規, 林 利彦, 山本 有平
日本形成外科学会会誌, 42, 7, 369, 374, (一社)日本形成外科学会, 2022年07月
日本語, 序論/目的:形成外科において他科と共同で行うチームサージャリーは重要な分野であるが、その症例の多くは他科入院であるため、病院経営に対する形成外科の経済的貢献度は明らかになりにくい。チームサージャリーにおける形成外科の貢献度を明らかにすべく、他科共同手術の検討を行い、新型コロナウイルス感染症(以下、COVID-19)が及ぼした影響について考察した。方法:2017〜2020年度の4年間に手術に協力した他科入院手術の検討を行った。結果:入院科はCOVID-19前では耳鼻咽喉科(31.4%)が最多であったが、COVID-19後では救急科(38.3%)が最多であった。COVID-19前後で形成外科入院総手術点数は減少したが、他科共同手術の形成外科手術点数は増加した。形成外科が関与した総手術点数は変化がなかった。結論:チームサージャリーにおける形成外科の貢献度とCOVID-19による影響が明らかにされた。幅広い領域において手術に協力することで、社会情勢や医療体制による影響を抑えられることが示された。(著者抄録)

リンパ節移植という局所外科的リンパ系再構築法がもたらす可能性 循環と免疫の観点から　　　　　　　　　　　　　　　
前田 拓, 石川 耕資, 村尾 尚規, 林 利彦, 古川 洋志, 舟山 恵美, 大澤 昌之, 山本 有平
リンパ学, 45, 1, 38, 41, 日本リンパ学会, 2022年06月
日本語

粉瘤様の外観を呈したPrimary dermal melanomaの治療経験　　　　　　　　　　　　　　　
草島 英梨香, 前田 拓, 石川 耕資, 三浦 隆洋, 舟山 恵美, 大澤 昌之, 吉田 哲也, 山本 有平
日本臨床皮膚外科学会総会・学術大会プログラム・抄録集, 40回, 31, 31, 日本臨床皮膚外科学会, 2022年05月
日本語

遊離空腸再建における合併症早期発見のためのカラーエコーの有用性について　　　　　　　　　　　　　　　
前田 拓, 林 利彦, 石川 耕資, 北條 正洋, 舟山 恵美, 三浦 隆洋, 山本 有平
頭頸部癌, 48, 2, 180, 180, (一社)日本頭頸部癌学会, 2022年05月
日本語

顕微鏡下マウスリンパ節移植モデルの開発 新たな材料を求めて　　　　　　　　　　　　　　　
北條 正洋, 前田 拓, 石川 耕資, 大澤 昌之, 舟山 恵美, 山本 有平
日本マイクロサージャリー学会学術集会プログラム・抄録集, 48回, 355, 355, (一社)日本マイクロサージャリー学会, 2021年12月
日本語

Combined internal and external negative pressure wound therapy: breakthrough treatment for lymphocutaneous intractable fistula
Takahiro Miura, Yuhei Yamamoto, Naoki Murao, Taku Maeda, Masayuki Osawa, Toshihiko Hayashi, Emi Funayama
Surgery Today, 51, 10, 1630, 1637, Springer Science and Business Media LLC, 2021年10月
研究論文（学術雑誌）

遊離広背筋弁で再建した頭蓋骨に及ぶIII度熱傷の1例
竹田 朋弘, 石川 耕資, 林 利彦, 前田 拓, 石井 陸, 佐々木 雄輝, 北條 正洋, 三浦 隆洋, 大澤 昌之, 舟山 恵美, 山本 有平
熱傷, 47, 3, 114, 121, (一社)日本熱傷学会, 2021年09月
日本語, 症例は76歳,女性.意識障害をきたし自宅の石油暖房機の前で倒れて頭部から頬部に熱傷を受傷した.初診時,左頭部に白色壊死を伴う14×11cm大のIII度熱傷を認めた.受傷後2日目の初回デブリードマンにより頭蓋骨露出を認めたが,周囲の帽状腱膜および骨膜は温存し人工真皮を移植した.露出した頭蓋骨,周囲の帽状腱膜および骨膜も壊死にいたり,広範囲に頭蓋骨が露出した.そのため受傷後17日目に良好な出血が得られるまで頭蓋骨外板を削り,遊離広背筋弁および筋弁上への網状植皮により再建した.熱傷深度が深く広範囲に頭蓋骨が露出した場合は,外板を削って肉芽増生後に植皮を行う方法は従来から行われてきたが,治癒まで長期間を要する.早期に血流の豊富な筋弁で被覆する方法は,露出骨の壊死の進行や感染を制御できる有用な再建法と考えられる.(著者抄録)

リンパ浮腫に対する最新研究と治療戦略 マウスリンパ節移植モデル リンパ節移植の循環系・免疫系作用に関する基礎研究
石川 耕資, 前田 拓, 草島 英梨香, 舟山 恵美, 林 利彦, 大澤 昌之, 古川 洋志, 山本 有平
リンパ学, 44, 1, 24, 27, 日本リンパ学会, 2021年07月
日本語

Breast reconstruction via fat grafting for a patient with bilateral congenital amastia ( Finlay‐Marks syndrome)
Riri Ito, Yuhei Yamamoto, Taku Maeda, Kosuke Ishikawa, Emi Funayama
Congenital Anomalies, 61, 4, 142, 143, Wiley, 2021年07月
研究論文（学術雑誌）

リンパ浮腫に対する最新研究と治療戦略 マウスリンパ節移植モデル リンパ節移植の循環系・免疫系作用に関する基礎研究
石川 耕資, 前田 拓, 草島 英梨香, 舟山 恵美, 林 利彦, 大澤 昌之, 古川 洋志, 山本 有平
リンパ学, 44, 1, 24, 27, 日本リンパ学会, 2021年07月
日本語

Topical Application of Conditioned Medium from Hypoxically Cultured Amnion-Derived Mesenchymal Stem Cells Promotes Wound Healing in Diabetic Mice.
Hiroko Takahashi, Shunsuke Ohnishi, Yuhei Yamamoto, Toshihiko Hayashi, Naoki Murao, Masayuki Osawa, Taku Maeda, Kosuke Ishikawa, Naoya Sakamoto, Emi Funayama
Plastic and reconstructive surgery, 147, 6, 1342, 1352, 2021年06月01日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Mesenchymal stem cells or their conditioned medium improve chronic wound healing, and their effect is enhanced by hypoxia. Diabetic foot ulcers are chronic wounds characterized by abnormal and delayed healing, which frequently require amputation. The authors evaluated the effect of topical application of conditioned medium from hypoxically cultured amnion-derived mesenchymal stem cells on wound healing in diabetic mice. METHODS: Amnion-derived mesenchymal stem cells were cultured under 21% oxygen to prepare normoxic conditioned medium and under 1% oxygen to prepare hypoxic conditioned medium. Hydrogels containing standard medium, normoxic conditioned medium, or hypoxic conditioned medium were topically applied to excisional wounds of mice with streptozotocin-induced diabetes. Ulcer tissues were harvested on day 9; immunohistochemical and quantitative polymerase chain reaction analyses were performed to analyze angiogenesis, inflammatory cell infiltration, and expression levels of inflammation-related genes. RESULTS: Hypoxic conditioned medium significantly enhanced wound closure, increased capillary density and epithelization, and reduced macrophage infiltration. It also tended to reduce the infiltration of neutrophils and enhance the infiltration of regulatory T cells; it showed a tendency to downregulate the expression of the inflammation-related genes interleukin-1β, interleukin-6, chemokine ligand 1, and chemokine ligand 2. Normoxic conditioned medium exhibited similar effects, although they were of lesser magnitude than those of hypoxic conditioned medium. CONCLUSIONS: Hydrogels containing hypoxically cultured, amnion-derived mesenchymal stem cell conditioned medium accelerated wound healing in diabetic mice by enhancing angiogenesis, accelerating epithelization, and suppressing inflammation. Therefore, topical application of amnion mesenchymal stem cell-derived hypoxic conditioned medium could be a novel treatment for diabetic foot ulcers.

Cleft lip in oto-palato-digital syndrome type I.
Erika Guilpain Kusajima, Taku Maeda, Naoki Murao, Emi Funayama, Yuhei Yamamoto
Congenital anomalies, 61, 3, 103, 104, 2021年05月, ［国際誌］
英語, 研究論文（学術雑誌）

Iatrogenic third-degree burn caused by off-label use of an infrared radiant heat lamp in a patient with accidental hypothermia
Kosuke Ishikawa, Taku Maeda, Toshihiko Hayashi, Ryuji Shichinohe, Naoki Murao, Masahiro Hojo, Riri Ito, Masayuki Osawa, Yuhei Yamamoto, Emi Funayama
Burns Open, 5, 1, 21, 24, Elsevier BV, 2021年01月
研究論文（学術雑誌）

Maggot debridement therapy in critical limb ischaemia: a case study.
Taku Maeda, Yuhei Yamamoto, Naoki Murao, Toshihiko Hayashi, Chu Kimura, Suguru Matsui, Tatsuya Saito, Hotaka Matsui, Masayuki Osawa, Emi Funayama
Journal of wound care, 29, Sup12, S28-S32, 2020年12月01日, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVE: In critical limb ischaemia (CLI), first-line therapy is revascularisation, but alternative treatment options are needed in certain cases. Maggot debridement therapy (MDT) is historically considered to be contraindicated in ischaemic ulcers. Wound care in patients with CLI is becoming increasingly diverse with the development of novel revascularisation strategies; therefore, CLI now needs to be reconsidered as an indication for MDT. METHOD: We retrospectively reviewed five legs with CLI (five male, one female) treated with MDT between January 2013 and December 2017. Changes in skin perfusion pressure (SPP) around the ulcer before and after MDT were evaluated. One or two cycles of MDT were performed (eight in total). We also evaluated the proportion of necrotic tissue in the ulcer and the presence of exposed necrotic bone. The proportion of necrotic tissue in the ulcer was classified as NT 1+ (<25%), NT 2+ (25-50%), NT 3+ (50-75%) or NT 4+ (>75%). RESULTS: When the proportion of necrotic tissue was >50%, with no exposed necrotic bone in the wound, an increase in SPP was observed after five (62.5%) of eight cycles of MDT. And with a proportion of necrotic tissue of <25% and/or exposed necrotic bone in the wound, a decrease in SPP was observed after three (37.5%) of eight cycles. Wound healing was accelerated in the presence of increased SPP. CONCLUSION: Effective MDT with increased SPP requires an ulcerative state of necrotic tissue grade > NT 3+, with no exposed necrotic bone.

Long-term outcomes and recurrence-free interval after the treatment of keloids with a standardized protocol.
T Maeda, E Funayama, Y Yamamoto, N Murao, M Osawa, K Ishikawa, T Hayashi
Journal of tissue viability, 2020年11月30日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Recurrence rates of keloids have generally been reported at one time point. However, the longer the duration after treatment, the greater the likelihood that such lesions will recur. In this study, we analysed the time to recurrence during long-term follow-up. MATERIAL AND METHODS: We retrospectively reviewed recurrence-free interval in 52 patients with keloid (age 8-79 years) who had been treated between June 2006 and January 2011 using a standardised protocol developed by our group. RESULTS: Mean duration of follow-up was 37.5 (range, 7-120) months in patients with keloid. Kaplan-Meier survival curves revealed a statistically significant difference in recurrence-free interval between ear keloids and keloids excluding ear keloids. Recurrence rate for keloids was high in the first 2 years after treatment. CONCLUSIONS: Kaplan-Meier analysis was useful for understanding the tendency of recurrence of keloids after treatment using a standardised protocol.

「頭頸部の難渋する良性疾患I(NF-1、血管疾患)」 口唇部の動静脈奇形に対する硬化療法・手術・レーザーによる複合的治療の検討　　　　　　　　　　　　　　　
石川 耕資, 村尾 尚規, 西尾 卓哉, 福田 摩莉佳, 竹田 朋弘, 藤田 宗純, 澤口 恵美, 舟山 恵美, 山本 有平, 佐々木 了
日本頭蓋顎顔面外科学会学術集会プログラム・抄録集, 38回, 83, 83, (一社)日本頭蓋顎顔面外科学会, 2020年11月
日本語

口蓋の潰瘍を伴う乳児血管腫に対するプロプラノロール内服による診断的治療の経験　　　　　　　　　　　　　　　
石川 耕資, 村尾 尚規, 西尾 卓哉, 福田 摩莉佳, 竹田 朋弘, 藤田 宗純, 澤口 恵美, 舟山 恵美, 山本 有平, 佐々木 了
日本頭蓋顎顔面外科学会学術集会プログラム・抄録集, 38回, 118, 118, (一社)日本頭蓋顎顔面外科学会, 2020年11月
日本語

A Comparison of Outcomes After Palatoplasty in Patients With Non-Syndromic Pierre Robin Sequence Versus Patients With Non-Syndromic Isolated Cleft Palate
Maeda Taku, Yuhei Yamamoto, Akihiko Oyama, Satoru Sasaki, Toshihiko Hayashi, Naoki Murao, Masayuki Osawa, Emi Funayama
The Journal of craniofacial surgery, 31, 8, 2231, 2234, NLM (Medline), 2020年11月01日
英語, 研究論文（学術雑誌）, The purpose of this retrospective study was to compare outcomes of cleft palate repair in patients with non-syndromic Pierre Robin sequence (NS-PRS) versus those with non-syndromic isolated cleft palate (NS-ICP). Pierre Robin sequence (PRS) was defined as a diagnosis of the triad of microretrognathia, glossoptosis, and cleft palate, and the severity of PRS was assessed based on the presence of respiratory and feeding problems. All patients underwent palatoplasty between January 2000 and December 2011. The authors examined age at palatoplasty, type of cleft palate, fistula rate, velopharyngeal (VP) function, nasal emission, hypernasality, and need for secondary speech surgery, in addition to PRS severity in the NS-PRS patients. A total of 15 NS-PRS patients and 40 NS-ICP patients were reviewed. The incidence of VP dysfunction, nasal emission, hypernasality, and secondary speech surgery was not significantly different between the NS-PRS patients and NS-ICP patients. Age at palatoplasty was significantly different between the 2 groups (P = 0.012) but type of CP was not (P = 1.00). Only 2 NS-PRS patients were classified as category III (severe), and all of the NS-PRS patients who had VP insufficiency were classified as PRS severity category I (not severe). The findings of this study indicate that NS-PRS patients may not have worse outcomes than NS-ICP patients.

A Comparison of Outcomes After Palatoplasty in Patients With Non-Syndromic Pierre Robin Sequence Versus Patients With Non-Syndromic Isolated Cleft Palate.
Maeda Taku, Yuhei Yamamoto, Akihiko Oyama, Satoru Sasaki, Toshihiko Hayashi, Naoki Murao, Masayuki Osawa, Emi Funayama
The Journal of craniofacial surgery, 2020年10月13日, ［国際誌］
英語, 研究論文（学術雑誌）, The purpose of this retrospective study was to compare outcomes of cleft palate repair in patients with non-syndromic Pierre Robin sequence (NS-PRS) versus those with non-syndromic isolated cleft palate (NS-ICP). Pierre Robin sequence (PRS) was defined as a diagnosis of the triad of microretrognathia, glossoptosis, and cleft palate, and the severity of PRS was assessed based on the presence of respiratory and feeding problems. All patients underwent palatoplasty between January 2000 and December 2011. The authors examined age at palatoplasty, type of cleft palate, fistula rate, velopharyngeal (VP) function, nasal emission, hypernasality, and need for secondary speech surgery, in addition to PRS severity in the NS-PRS patients. A total of 15 NS-PRS patients and 40 NS-ICP patients were reviewed. The incidence of VP dysfunction, nasal emission, hypernasality, and secondary speech surgery was not significantly different between the NS-PRS patients and NS-ICP patients. Age at palatoplasty was significantly different between the 2 groups (P = 0.012) but type of CP was not (P = 1.00). Only 2 NS-PRS patients were classified as category III (severe), and all of the NS-PRS patients who had VP insufficiency were classified as PRS severity category I (not severe). The findings of this study indicate that NS-PRS patients may not have worse outcomes than NS-ICP patients.

Ulcerated Infantile Hemangioma of the Hard Palate: Diagnostic Treatment With Oral Propranolol
Kosuke Ishikawa, Munezumi Fujita, Tomohiro Takeda, Shintaro Mitamura, Takuya Nishio, Emi Funayama, Toshihiko Hayashi, Masayuki Osawa, Taku Maeda, Yuhei Yamamoto, Satoru Sasaki
The Journal of craniofacial surgery, 31, 6, e600, e602, NLM (Medline), 2020年09月01日
英語, 研究論文（学術雑誌）, Infantile hemangiomas arising in the palate are rare. The authors describe a case of ulcerated infantile hemangioma of the hard palate with feeding difficulty. To our knowledge, this is the first reported case of immunohistochemically diagnosed palatal infantile hemangioma successfully treated using oral propranolol.

Ulcerated Infantile Hemangioma of the Hard Palate
Kosuke Ishikawa, Munezumi Fujita, Tomohiro Takeda, Shintaro Mitamura, Takuya Nishio, Emi Funayama, Toshihiko Hayashi, Masayuki Osawa, Taku Maeda, Yuhei Yamamoto, Satoru Sasaki
Journal of Craniofacial Surgery, Publish Ahead of Print, Ovid Technologies (Wolters Kluwer Health), 2020年07月03日
研究論文（学術雑誌）

カルシフィラキシーに対する創部ケア 周期的持続灌流を併用した陰圧閉鎖療法による新規アプローチ法(Wound Care for Calciphylaxis: A Novel Approach for Wound Management with Negative Pressure Wound Therapy with Instillation and Dwell Time)
Guilpain Kusajima Erika, Yamamoto Yuhei, Murao Naoki, Hayashi Toshihiko, Osawa Masayuki, Maeda Taku, Ishikawa Kosuke, Horiuchi Katsumi, Matsui Suguru, Saito Tatsuya, Matsui Hotaka, Funayama Emi
International Journal of Surgical Wound Care, 1, 1, 20, 26, (一社)日本創傷外科学会, 2020年06月
英語

Wound Care for Calciphylaxis
Erika Guilpain Kusajima, Yuhei Yamamoto, Naoki Murao, Toshihiko Hayashi, Masayuki Osawa, Taku Maeda, Kosuke Ishikawa, Katsumi Horiuchi, Suguru Matsui, Tatsuya Saito, Hotaka Matsui, Emi Funayama
International Journal of Surgical Wound Care, 1, 1, 20, 26, Japan Society for Surgical Wound Care, 2020年
研究論文（学術雑誌）

Application of Negative-pressure Wound Therapy after Radical Excision of Soft Tissue Malignancy
Taku Maeda, Naoki Murao, Toshihiko Hayashi, Emi Funayama, Masayuki Osawa, Kosuke Ishikawa, Yuhei Yamamoto
International Journal of Surgical Wound Care, 1, 2, 47, 52, Japan Society for Surgical Wound Care, 2020年
研究論文（学術雑誌）

眼外胚葉症候群(Oculoectodermal syndrome)の治療経験　　　　　　　　　　　　　　　
開田 ひろみ, 村尾 尚規, 舟山 恵美, 石川 耕資, 高橋 周子, 山本 有平
日本形成外科学会会誌, 39, 12, 623, 629, (一社)日本形成外科学会, 2019年12月
日本語, 症例は生後8日の男児で、出生時より頭頂部を中心に皮膚欠損創、左上眼瞼の部分欠損を認めた。その他、結膜デルモイド、くも膜嚢胞を疑う所見を認めたため眼外胚葉症候群が疑われた。頭部、眼瞼の皮膚欠損に対する加療目的に当科へ紹介となった。頭部皮膚欠損症、眼症状(上眼瞼欠損や眼球結膜デルモイド)に加え、くも膜嚢胞などの脳MRI所見より、眼外胚葉症候群の診断となった。角膜上皮障害に対しては眼軟膏の外用などの保存的治療を行い経過観察した。整容面や角膜上皮障害の改善目的で、眼瞼の組織量が増加する3歳時に左上眼瞼形成術を施行した。5歳時に左大腿部の瘤痛による跛行を認め、多発性の非骨化性線維腫として矛盾しない所見であった。現在、整形外科で骨皮質の形成を期待して経過観察中である。

Squamous cell carcinoma arising in a chronic leg ulcer in Klippel-Trenaunay syndrome after the Charles procedure: A case with 40 years of follow up.
Ishikawa K, Funayama E, Yamamoto Y, Furukawa H, Hayashi T, Murao N, Osawa M, Maeda T, Fujita M, Sasaki S
The Journal of dermatology, 46, 11, e403, e405, 2019年11月, ［査読有り］, ［国際誌］
英語

Advancement Flap Using Excess Skin for Upper Eyelid Full-Thickness Defects.
Ito R, Maeda T, Yamamoto Y, Funayama E, Murao N, Osawa M, Ishikawa K, Ikeda M, Hayashi T
The Journal of craniofacial surgery, 30, 8, 2614, 2616, 2019年11月, ［査読有り］

先天性顔面神経麻痺に対するネットワーク型神経再建を行った1例
古川 洋志, 山本 有平, 前田 拓, 林 利彦, 大澤 昌之, 舟山 恵美, 七戸 龍司
日本頭蓋顎顔面外科学会誌, 35, 3, 84, 88, (一社)日本頭蓋顎顔面外科学会, 2019年09月
日本語, 4歳女児。側頭骨内腫瘍による右顔面神経の圧迫が原因と思われる先天性顔面神経麻痺に対して1歳半時に右顔面神経減荷術と腫瘍摘出術が行われ、術後は一時的に改善したが、3歳時に不全麻痺と診断された。4歳で紹介受診し、顔面神経刺激での誘発筋電図で一部の患側表情筋に誘発電位を認めたため、ネットワーク型神経再建の適応と判断して手術を行った。右大耳介神経を採取して右舌下神経と右顔面神経との間にクロスリンク型に移植し、術後合併症を認めることなく経過したが、術後9年で表情筋の回復は認めず、改善が得られなかった最大の理由として発症から4年以上経過していることが考えられた。

Oculo-auriculo-fronto-nasal syndrome with duane retraction syndrome and dysplastic bony structure in the midline of nose
Ito R, Osawa M, Yamamoto Y, Murao N, Hayashi T, Maeda T, Ishikawa K, Oyama A, Funayama E
The Journal of Craniofacial Surgery, 30, 6, e576, e578, 2019年09月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Oculo-auriculo-fronto-nasal syndrome (OAFNS) is a rare anomaly characterized by features overlapping those of frontonasal dysplasia (FND) and the oculo-auriculo-vertebral spectrum (OAVS).1 The FND features malformation of frontonasal process-derived structures, characterized by anomalies in the central portion of the face. The OAVS is characterized by developmental anomalies of the first and second pharyngeal arches. The OAFNS is a condition with clinical features of both FND and OAVS. Here, the authors present the case of a male with OAFNS who not only exhibited typical OAFNS symptoms but also a dysplastic bony structure that bridged the anterior nasal spine and inferior nasal bones, and unilateral type 3 Duane retraction syndrome (absence of right-eye abduction). Abnormal nasal bones are characteristic of OAFNS; such abnormalities are absent from FND and OAVS. The authors reduced the dysplastic nasal bony structure via open external rhinoplasty, followed by lateral nasal osteotomy when he was 16 years of age. The nasal dorsum appeared natural after surgery and he was satisfied with the result.

Wound-healing problems associated with combined vascular malformations in Klippel–Trenaunay syndrome
Ishikawa K, Yamamoto Y, Funayama E, Furukawa H, Sasaki S
Advances in Wound Care, 8, 6, 246, 255, 2019年06月, ［査読有り］, ［招待有り］
英語, 研究論文（学術雑誌）, Significance: In Klippel–Trenaunay syndrome (KTS), management of a wound in the affected limb can be difficult because of the underlying vascular malformations present. This review describes the characteristics of KTS with wound complications in light of the genetic and molecular mechanisms of the disease. Recent Advances: KTS is a slow-flow combined vascular malformation characterized by the triad of capillary malformation, venous malformation with or without lymphatic malformation, and limb overgrowth. KTS is encompassed within the phosphatidylinositol-4,5-bisphosphate3-kinase catalytic subunit alpha (PIK3CA)-related overgrowth spectrum (PROS), having recently been linked to activating mutations in the PIK3CA gene. This clearly has implications for both molecular diagnosis and potential treatment strategies for the disease. Critical Issues: KTS should be distinguished from Parkes Weber syndrome, a fast-flow-type combined vascular malformation with limb overgrowth. Individualized management is needed for KTS and should be focused on the treatment of symptoms. Future Directions: Targeted therapies that inhibit the phosphoinositide 3-kinase signaling pathway are a potential treatment option for PROS.

Changes in high endothelial venules in lymph nodes after vascularized and nonvascularized lymph node transfer in a murine autograft model.
Ishikawa K, Funayama E, Maeda T, Hayashi T, Murao N, Osawa M, Ito R, Furukawa H, Oyama A, Yamamoto Y
Journal of surgical oncology, 119, 6, 700, 707, 2019年05月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND AND OBJECTIVES: Vascularized lymph node transfer (LNT) is gaining popularity in the treatment of lymphedema. However, it is unclear whether the vascularization of transferred lymph nodes (LNs) contributes to functional improvement. High endothelial venules (HEVs) are specialized vessels that allow lymphocytes to enter LNs. In this study, we compared the numbers of HEVs and lymphocytes in LNs after vascularized and nonvascularized LNT. METHODS: Fifty mice were divided into three groups (group 1, pedicled vascularized LNT; group 2, pedicled nonvascularized LNT; group 3, free nonvascularized LNT). Afferent lymphatic reconnection was confirmed by patent blue staining. The transferred LNs were harvested 4 weeks after surgery. HEVs, B-cells, and T-cells were subjected to immunohistochemical staining and quantified. RESULTS: Afferent lymphatic reconnection was observed in 13 of 20 transferred LNs in group 1, 11 of 15 in group 2, and 7 of 15 in group 3. The ratio of dilated/total HEVs in transferred LNs with afferent lymphatic reconnection was significantly higher in group 1 than in groups 2 and 3. No significant differences in numbers of B-cells and T-cells were found in the transferred LNs. CONCLUSIONS: We found that more functional HEVs were preserved in cases with successful afferent lymphatic reconnection after vascularized LNT than after nonvascularized LNT.

Feasibility of pedicled vascularized inguinal lymph node transfer in a mouse model: A preliminary study.
Ishikawa K, Maeda T, Funayama E, Hayashi T, Murao N, Osawa M, Furukawa H, Oyama A, Yamamoto Y
Microsurgery, 39, 3, 247, 254, 2019年03月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, PURPOSE: Vascularized lymph node transfer is becoming more common in the treatment of lymphedema, but suitable small animal models for research are lacking. Here, we evaluated the feasibility of pedicled vascularized inguinal lymph node transfer in mice. METHODS: Twenty-five mice were used in the study. An inguinal lymph node-bearing flap with a vascular pedicle containing the superficial caudal epigastric vessels was transferred into the ipsilateral popliteal fossa after excision of the popliteal lymph node. Indocyanine green (ICG) angiography was used to confirm vascularity of the flap. ICG lymphography was performed to evaluate lymphatic flow at 3 and 4 weeks postoperatively. Patent blue dye was injected into the ipsilateral hind paw to observe staining of the transferred lymph node at 4 weeks postoperatively. All transferred lymph nodes were then harvested and histologically evaluated by hematoxylin and eosin staining. RESULTS: In 16 of the 25 mice, ICG lymphography showed reconnection between the transferred lymph node and the afferent lymphatic vessels, as confirmed by patent blue staining. Histologically, these transferred lymph nodes with afferent lymphatic reconnection significantly regressed in size (0.37 ± 0.24 mm2 ) and showed clear follicle formation, whereas those without afferent lymphatic reconnection showed less size regression (1.31 ± 1.17 mm2 ); the cell population was too dense to allow identification of follicles. CONCLUSIONS: We established a mouse model of vascularized lymph node transfer with predictable afferent lymphatic reconnection. Both the vascularization and reconnection might be necessary for functional regeneration of the transferred lymph node.

NEDD4 Is Involved in Inflammation Development during Keloid Formation.
Fujita M, Yamamoto Y, Jiang JJ, Atsumi T, Tanaka Y, Ohki T, Murao N, Funayama E, Hayashi T, Osawa M, Maeda T, Kamimura D, Murakami M
The Journal of investigative dermatology, 139, 2, 333, 341, 2019年02月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Keloids mark a chronic inflammatory disease characterized by a fibroproliferative disorder of the skin. A genome-wide association study showed that single-nucleotide polymorphism rs8032158 in the neural precursor cell-expressed NEDD4 gene, which has six protein-coding transcript variants (TVs), is genetically linked to keloids. Here, we show that the high frequency of risk allele C in rs8032158 in keloid patients is associated with a selectively higher expression of TV3 of NEDD4 to activate the NF-κB pathway. Comparisons of keloid scars with normal skin samples that do not have the single-nucleotide polymorphism allele and were derived from different anatomical sites showed stronger expressions of NEDD4 TV3 and activated forms of NF-κB and STAT3 in keloid scars. Forced expression or selective knockdown of NEDD4 TV3 increased or decreased NF-κB activation in vitro. Furthermore, NEDD4 knockdown suppressed NF-κB-dependent inflammation development in vivo. Mechanistic analysis showed that NEDD4 TV3 is involved in NF-κB activation through its association with the adaptor protein RIP. These results suggest that NEDD4 TV3 is a potential diagnostic marker and therapeutic target for chronic skin diseases, including keloid.

Combination laser therapy as a non-surgical method for treating congenital melanocytic nevi from cosmetically sensitive locations on the body.
Funayama E, Yamamoto Y, Oyama A, Murao N, Hayashi T, Maeda T, Furukawa H, Osawa M
Lasers in medical science, 34, 9, 1925, 1928, 2019年02月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）

Comparison of Nasal Symmetry Between Presurgical Nasal Stenting and Postsurgical Nasal Retainer Placement in Unilateral Clefts.
Funayama E, Yamamoto Y, Oyama A, Furukawa H, Murao N, Hayashi T, Maeda T, Osawa M
The Journal of craniofacial surgery, 30, 1, 133, 136, 2019年01月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, The timing of cleft lip nose surgery remains controversial. The less invasive the procedure at the time of primary cleft lip repair, the less the growth and development of the nose is affected. Therefore, the nasal-stenting component of presurgical nasoalveolar molding has increasingly been used. However, not all cleft centers use such treatment. Conventional postsurgical placement of silicone nasal retainers remains popular. No report has yet compared presurgical nasal stenting (preNS) and postsurgical nasal retainer placement (postNR). In this study, postoperative nasal form outcomes after primary lip repair using preNS or postNR in patients with complete unilateral cleft lips, alveoli, and palates were compared. Patients in whom preNS alone was used for 6 months (group I) were compared with those receiving postNR (no preNS) for 6 months after primary nasal cartilage dissection (group II) and controls with no appliance (group III). Nasal anthropometric distances and angular relationships were measured photographically to assess nasal symmetry at 4 years of age in all groups. Compared to group III, groups I and II exhibited significantly greater nostril heights (P = 0.0075, P = 0.0015 respectively) and columellar deviation angles (P = 0.0020, P = 0.0221). Groups I and II did not differ significantly. No significant between-treatment difference in terms of nasal symmetry between preNS and postNR was observed. However, both treatments afforded significantly better results than no treatment. Since older infants tend to resist the placement of nasal devices, preNS is more feasible in this age group.

Our techniques for secondary alveolar bone grafting　　　　　　　　　　　　　　　
Masayuki Osawa, Akihiko Oyama, Emi Funayama, Yuhei Yamamoto
Japanese Journal of Plastic Surgery, 61, 7, 824, 834, Kokuseido Publishing Co. Ltd, 2018年07月01日
日本語, 研究論文（学術雑誌）, Secondary alveolar bone grafting is an essential surgical procedure in a series of treatments for cleft lip and palate. However, it is sometimes difficult to prepare the bed for safe alveolar bone grafting owing to the effects of prior surgery, such as primary lip plasty or palatoplasty. In this article, we describe techniques to deal with pitfalls associated with difficult cases experienced in our department to improve outcomes in alveolar bone grafting.

チームサージャリーにおける形成外科の貢献に関する10年間の検討　　　　　　　　　　　　　　　
石川 耕資, 古川 洋志, 小山 明彦, 舟山 恵美, 林 利彦, 村尾 尚規, 大澤 昌之, 前田 拓, 関堂 充, 山本 有平
日本形成外科学会会誌, 38, 6, 277, 282, (一社)日本形成外科学会, 2018年06月
日本語, 序論:チームサージャリーにおける形成外科の貢献度は明らかになりにくい。方法:2007〜2016年度に手術に協力した他科入院手術を前期と後期に分け、入院料、手術点数、形成外科の手術時間、人数を検討した。結果:他科共同手術は年平均65.5例(前期63.0例、後期68.0例)、入院科は耳鼻咽喉科25.2%、口腔外科・口腔内科23.8%が多くを占めた。他科共同手術における形成外科手術点数は、総手術点数の年平均58.1%(前期55.0%、後期61.1%)を占め、これは形成外科入院総手術点数の年平均33.9%(前期32.3%、後期35.5%)に相当した。他科共同手術における形成外科手術時間は、年平均294時間(4.5時間/件)、手術に参加した形成外科医は、年平均238人(3.6人/件)であった。結論:本検討によりチームサージャリーにおける形成外科の貢献度、形成外科におけるチームサージャリーの重要性が増していることが判明した。(著者抄録)

チームサージャリーにおける形成外科の貢献に関する10年間の検討　　　　　　　　　　　　　　　
石川 耕資, 古川 洋志, 小山 明彦, 舟山 恵美, 林 利彦, 村尾 尚規, 大澤 昌之, 前田 拓, 関堂 充, 山本 有平
日本形成外科学会会誌, 38, 6, 277, 282, (一社)日本形成外科学会, 2018年06月, ［査読有り］
日本語, 序論:チームサージャリーにおける形成外科の貢献度は明らかになりにくい。方法:2007〜2016年度に手術に協力した他科入院手術を前期と後期に分け、入院料、手術点数、形成外科の手術時間、人数を検討した。結果:他科共同手術は年平均65.5例(前期63.0例、後期68.0例)、入院科は耳鼻咽喉科25.2%、口腔外科・口腔内科23.8%が多くを占めた。他科共同手術における形成外科手術点数は、総手術点数の年平均58.1%(前期55.0%、後期61.1%)を占め、これは形成外科入院総手術点数の年平均33.9%(前期32.3%、後期35.5%)に相当した。他科共同手術における形成外科手術時間は、年平均294時間(4.5時間/件)、手術に参加した形成外科医は、年平均238人(3.6人/件)であった。結論:本検討によりチームサージャリーにおける形成外科の貢献度、形成外科におけるチームサージャリーの重要性が増していることが判明した。(著者抄録)

斗南病院における血管奇形患者116例の血液凝固系についての検討　　　　　　　　　　　　　　　
藤田 宗純, 佐々木 了, 石川 耕資, 舟山 恵美, 山本 有平
日本形成外科学会会誌, 38, 4, 183, 191, (一社)日本形成外科学会, 2018年04月
日本語, 序論:静脈奇形(venous malformation;以下VM)に代表される血管奇形の患者では、奇形血管内での凝固因子大量消費による凝固系異常(localized intravascular coagulopathy;以下LIC)を呈することが報告されている。方法:今回、斗南病院における116例の血管奇形患者の血液凝固系検査データについて検討した。結果:VMで最も多くLIC症例を認め、63例中21例であった。さらにVMでは、体表面積100cm2以上の病変、多発性の病変、症候群を有する症例では、DダイマーやFDPの上昇、フィブリノーゲンの低下がみられた。考察:上記の結果は、LICの病態の特徴であり、特に巨大VMや全身多発性VMの場合、LICをきたしている可能性が高い。結論:巨大VMや全身多発性VMの患者では、定期的にDダイマーやFDP、フィブリノーゲンの検査を行う必要があると考えられたため、報告した。(著者抄録)

Lymphatic Reconnection and Restoration of Lymphatic Flow by Nonvascularized Lymph Node Transplantation: Real-Time Fluorescence Imaging Using Indocyanine Green and Fluorescein Isothiocyanate-Dextran
Taku Maeda, Yuhei Yamamoto, Daisuke Iwasaki, Toshihiko Hayashi, Emi Funayama, Akihiko Oyama, Naoki Murao, Hiroshi Furukawa
Lymphatic Research and Biology, 16, 2, 165, 173, Mary Ann Liebert Inc., 2018年04月01日, ［査読有り］
英語, 研究論文（学術雑誌）, Background: Lymph node transplantation is being increasingly recognized as a method of reconstruction of the lymphatic system for the treatment of lymphedema. However, the mechanisms regulating the connections between the lymphatic vessels and the lymph nodes remain poorly understood. The objective of this study was to examine whether removal of a popliteal lymph node (PLN) could result in rerouting of lymph flow and whether a single transplanted nonvascularized lymph node could reconnect with a lymphatic vessel and restore lymph flow. Methods and Results: Thirty-six mice were allocated to undergo resection of a PLN alone (group 1) or a transplanted lymph node after resection of a PLN (group 2). Changes in lymph flow were observed using indocyanine green dye. The ability of the transplanted lymph node to reconnect with the lymphatic vessels was examined by fluorescein isothiocyanate (FITC)-dextran and immunohistochemical staining. In group 1, the flow of lymph was redirected to an inguinal lymph node (ILN) in 8 of 18 mice and continued to drain to the PLN in 10 mice. In group 2, the lymph continued to drain normally after removal of the PLN, and was also directed to an ILN in two mice. FITC-dextran demonstrated continuity of the transplanted PLN and the lymphatic vessels. Immunohistochemical staining showed that T cell and B cell populations in the transplanted lymph node were preserved. Conclusion: Lymphatic flow was rerouted after lymph node resection. A transplanted lymph node can be made viable with normal lymph flow by reconnecting the transplanted lymph node to a lymphatic vessel.

Immune-mediated antitumor effect of a transplanted lymph node.
Maeda T, Hayashi T, Furukawa H, Iwasaki D, Ishikawa K, Funayama E, Murao N, Osawa M, Oyama A, Yamamoto Y
International journal of cancer, 143, 5, 1224, 1235, 2018年03月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Lymph node (LN) transplantation is a recognized method for reconstruction of the lymphatic system and is used in the clinical setting to treat lymphedema. However, it is unclear whether transplanted LNs contribute to immune surveillance. In our study, we investigated whether a single transplanted non-vascularized LN, defined as a tumor-draining transplanted lymph node (TDTLN), could exert an immune-mediated antitumor effect. LN and lung metastases and primary tumor enlargement were evaluated in mice that were inoculated with B16-F10-luc2 melanoma cells in a hind limb footpad without (group 1) and with (group 2) popliteal lymph node (PLN) resection and in mice that underwent LN transplantation after PLN resection (group 3). The function of a TDTLN (group 3) and a tumor-draining popliteal lymph node (TDPLN; group 1) was evaluated in the context of cancer. LN and lung metastases were significantly aggravated by PLN resection but were significantly decreased by LN transplantation. Immunohistochemistry showed that the TDTLNs retained T-cells and B-cells and fluorescence-activated cell sorting analysis confirmed expansion of lymphocytes in these nodes; however, the degree of expansion in TDTLNs was different from that in TDPLNs. Expression of cytokines associated with immunostimulation was confirmed in the TDTLNs as well as in the TDPLNs. One of the differences in the immune-mediated antitumor effect of the TDPLNs and TDTLNs was ascribed to a difference in the site of lymphocyte homing to peripheral LNs through high endothelial venules. Non-vascularized LN transplantation had an immune-mediated antitumor effect.

Conditioned Medium Obtained from Amnion-Derived Mesenchymal Stem Cell Culture Prevents Activation of Keloid Fibroblasts.
Sato C, Yamamoto Y, Funayama E, Furukawa H, Oyama A, Murao N, Hosono H, Kawakubo K, Sakamoto N, Ohnishi S
Plastic and reconstructive surgery, 141, 2, 390, 398, LIPPINCOTT WILLIAMS & WILKINS, 2018年02月, ［査読有り］
英語, 研究論文（学術雑誌）, Background: Mesenchymal stem cells are a valuable cell source in regenerative medicine, and conditioned medium obtained from mesenchymal stem cells reportedly inhibits inflammation. Keloids are characterized by abnormal fibrosis, caused by fibroblasts in response to inflammation. In this study, the authors evaluated whether conditioned medium obtained from amnion-derived mesenchymal stem cells suppressed activation of keloid fibroblasts.Methods: Keloid (n = 7), mature (n = 5), and normal (n = 5) fibroblasts were harvested from patients. Fibroblasts were stimulated with transforming growth factor (TGF)-beta, and the effects of conditioned medium obtained from amni-on-derived mesenchymal stem cells on cell proliferation, activation, and expression of extracellular matrix-related genes were analyzed. The effect of concentrating the conditioned medium by ultrafiltration on fibroblast activation was also analyzed.Results: Conditioned medium obtained from amnion-derived mesenchymal stem cells significantly up-regulated proliferation of mature fibroblasts but tended to suppress that of keloid fibroblasts. Conditioned medium obtained from amnion-derived mesenchymal stem cells significantly suppressed the TGF-ss-induced up-regulation of a-smooth muscle actin in keloid and normal fibroblasts and collagen I in keloid fibroblasts, but not in mature fibroblasts. The conditioned medium obtained from amnion-derived mesenchymal stem cells concentrated by ultrafiltration and the filtrate significantly suppressed TGF-ss-induced a-smooth muscle actin expression.Conclusion: Conditioned medium obtained from amnion-derived mesenchymal stem cells prevents proliferation and activation of keloid fibroblasts and is a promising keloid treatment for administration as a topical agent.

Apert症候群との鑑別を要したoral-facial-digital syndrome type Iの1例　　　　　　　　　　　　　　　
伊藤 梨里, 小山 明彦, 林 利彦, 舟山 恵美, 古川 洋志, 山本 有平
日本頭蓋顎顔面外科学会誌, 33, 4, 132, 136, (一社)日本頭蓋顎顔面外科学会, 2017年12月
日本語, 4ヵ月女児。生下時より軟口蓋裂、舌裂、頬小帯の形成、両手第2・3指間の合指症を認め、頭位は生下時36.0cmから1週間に0.6cm拡大を呈して小泉門の膨隆を認めた。顔面には多発する小丘疹を認めApert症候群を疑ったが、生後6ヵ月時の頭部CT・MRIで脳梁の低形成、多房性の半球間裂嚢胞を認めた。頭蓋縫合の早期癒合は認めず、小泉門の膨隆および脳圧亢進は嚢胞内への嚢液貯留によるものであり、Apert症候群は否定された。臨床所見、画像所見から総合的にOral-facial-digital syndrome type Iと診断し、生後7ヵ月時にクモ膜嚢胞-腹腔シャント術を施行し、1歳11ヵ月時にFurlow法による軟口蓋形成術を施行した。6歳時に咽頭弁形成術を施行し、経過観察中である。

Vesiculobullous melanoma: an unusual manifestation of in-transit metastasis
E. Kusajima, H. Furukawa, E. Funayama, A. Oyama, T. Mitsuhashi, Y. Yamamoto
CLINICAL AND EXPERIMENTAL DERMATOLOGY, 42, 7, 767, 770, WILEY, 2017年10月, ［査読有り］
英語, 研究論文（学術雑誌）, Malignant melanoma (MM), a well-known skin cancer with a poor prognosis, has various clinical manifestations, but vesiculobullous lesions have seldom been reported. We report a case of MM forming amelanotic vesicles at the site of an in-transit metastasis, and we also review the published reports on vesiculobullous MM. Our patient was an 87-year-old man with a history of a treated plantar MM 2 years previously, who had recurrence of the MM and development of an in-transit metastasis in his lower leg. Histopathological findings revealed vesicles caused by infiltration of the tumour. A review of the English literature revealed nine cases with various clinical presentations of the vesicles or blisters. For patients with MM with vesiculobullous lesions, an accurate medical history and examination of biopsies are of primary importance for management.

Transarterial Embolization and Transmucosal Sclerotherapy That Led to Successful Deliveries in a Patient With Symptomatic Arteriovenous Malformation of the Tongue
Munezumi Fujita, Yuhei Yamamoto, Satoru Sasaki, Akihiko Oyama, Emi Funayama, Hiroshi Furukawa
JOURNAL OF CRANIOFACIAL SURGERY, 28, 7, E675, E678, LIPPINCOTT WILLIAMS & WILKINS, 2017年10月, ［査読有り］
英語, 研究論文（学術雑誌）, Patients with arteriovenous malformations (AVMs) are at risk of significant hemorrhage and AVMs are especially difficult to manage in those desiring future pregnancy. Few patients with successful deliveries have been previously reported. The authors report an unusual case of AVM of the tongue in a pregnant woman who presented with massive pulsatile bleeding from a ruptured artery in the tongue in late gestation, this was thought to be caused by the changes in hormonal balance and the increase in cardiac output. The bleeding was controlled with transarterial embolization and transmucosal absolute ethanol sclerotherapy. Furthermore, her second and third deliveries were successfully managed.
The authors managed symptomatic tongue AVM by combining transarterial embolization and transmucosal sclerotherapy, which was followed by successful deliveries. This patient supports the utility of transmucosal absolute ethanol sclerotherapy for tongue AVM and multidisciplinary medical care for a successful delivery.

Factors that Affected Functional Outcome After a Delayed Excision and Split-Thickness Skin Graft on the Dorsal Side of Burned Hands
Ryuji Shichinohe, Yuhei Yamamoto, Kunihiro Kawashima, Chu Kimura, Kentaro Ono, Katsumi Horiuchi, Tetsunori Yoshida, Naoki Murao, Toshihiko Hayashi, Emi Funayama, Akihiko Oyama, Hiroshi Furukawa
JOURNAL OF BURN CARE & RESEARCH, 38, 5, E851, E858, LIPPINCOTT WILLIAMS & WILKINS, 2017年09月, ［査読有り］
英語, 研究論文（学術雑誌）, Early excision and skin grafting is the principle treatment for a burned hand although there are occasions when it cannot be done such as severe general condition, delayed consultation, and the lack of a definitive assessment of burn depth. This study analyzes the factors that affected function after a delayed excision and skin graft for hands with a deep dermal burn. This study retrospectively evaluated 43 burned hands that required a delayed excision and split-thickness skin graft on the dorsal side. Cases were required to only have split-thickness skin grafting from the dorsum of the hand and fingers distally to at least the proximal interphalangeal joint at least 8 days after the injury. The hands were divided into two functional categories: Functional category A, normal or nearly normal joint movements, and functional category B, abnormal joint movements. Demographic data were assessed statistically by a univariate analysis following a multiple regression analysis by a stepwise selection. A significant difference was observed between the groups in the number of days from grafting to complete wound healing of the graft site and with or without an escharotomy in the analysis. These parameters were statistically significant predictors of functional category B. The functional outcome of a burned hand after a delayed excision and split-thickness skin graft on the dorsal side became degraded depending on the number of days from grafting to complete wound healing. Cases that underwent an escharotomy also showed deterioration in function.

Dominant lymph drainage patterns in the occipital and parietal regions: evaluation of lymph nodes in patients with skin cancer of the head
Taku Maeda, Yuhei Yamamoto, Hiroshi Furukawa, Akihiko Oyama, Emi Funayama, Naoki Murao, Toshihiko Hayashi
INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY, 22, 4, 774, 779, SPRINGER JAPAN KK, 2017年08月, ［査読有り］
英語, 研究論文（学術雑誌）, Background The purpose of this study was to evaluate the superficial lymph drainage patterns of primary skin cancers of the head arising from the occipital or parietal region.
Method The dominant patterns of lymph drainage were retrospectively reviewed in eight patients aged 36-85 years with skin cancers in the occipital or parietal region in whom sentinel lymph node biopsy or lymph node dissection had been performed at Hokkaido University Hospital between January 1981 and December 2015.
Results Lymph drainage was mainly to the occipital (6/8, 75%), level II (5/8, 63%), and level V lymph nodes (5/8, 63%). Of the six patients with drainage to the occipital lymph nodes, four (67%) also had drainage to level V nodes.
Conclusions The dominant lymph drainage pattern in patients with skin cancer arising from the occipital or parietal region was to the occipital, level II, and level V lymph nodes. Further, lymph tended to drain directly from the occipital region to the level V lymph nodes.

下顎再建後のプレート露出に対するVAC治療システムおよび高気圧酸素療法を用いた集学的治療　　　　　　　　　　　　　　　
前田 拓, 林 利彦, 古川 洋志, 村尾 尚規, 小山 明彦, 舟山 恵美, 山本 有平
日本形成外科学会会誌, 37, 6, 332, 332, (一社)日本形成外科学会, 2017年06月
日本語

Hinged mastoid fascial flapを用いたトリーチャーコリンズ症候群のlow hairline microtiaの再建　　　　　　　　　　　　　　　
前田 拓, 小山 明彦, 舟山 恵美, 古川 洋志, 林 利彦, 村尾 尚規, 山本 有平
日本形成外科学会会誌, 37, 6, 344, 344, (一社)日本形成外科学会, 2017年06月
日本語

Review and proposal of regional surgical management for melanoma: revisiting of integumentectomy and incontinuity dissection in treatment of skin melanoma
Toshihiko Hayashi, Hiroshi Furukawa, Takashi Kitamura, Ryuji Shichinohe, Naoki Murao, Akihiko Oyama, Emi Funayama, Taku Maeda, Yuhei Yamamoto
INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY, 22, 3, 569, 576, SPRINGER JAPAN KK, 2017年06月, ［査読有り］
英語, Background Past studies showed that integumentectomy and incontinuity could be effective procedures in the surgical management of melanoma patients. The present study reports on the historical background of these procedures. In addition, we analyze the ICG assisted integumentectomy and incontinuity techniques and algorithms that we had created when performing this procedure.
Method In accordance with our algorithm, we performed ICG assisted integumentectomy/incontinuity procedures on 17 patients with stage III melanomas between 2008 and 2016. We also investigated the locoregional recurrence rate in a control group comprising 60 patients at stage III without using the algorithm.
Results The former group exhibited a tendency of locoregional recurrence rate suppression. Melanoma cells in the dissected intervening tissue were microscopically identified in 2 out of 17 cases.
Conclusions Our ICG assisted integumentectomy or incontinuity procedures could be effective in controlling locoregional recurrence rates in melanoma cases. Moreover, our method can be generally applied because the dissection is only performed within the lymphatic pathway region identified using indocyanine green.

Full-Thickness Entire Nasal Alar Reconstruction Using a Forehead Flap in Asians: No Cartilaginous Infrastructural Lining Is Necessary
Emi Funayama, Yuhei Yamamoto, Hiroshi Furukawa, Naoki Murao, Ryuji Shichinohe, Takeshi Yamao, Toshihiko Hayashi, Akihiko Oyama
JOURNAL OF CRANIOFACIAL SURGERY, 28, 3, 734, 737, LIPPINCOTT WILLIAMS & WILKINS, 2017年05月, ［査読有り］
英語, 研究論文（学術雑誌）, Full-thickness defects of the entire nasal ala, including the rim, can be challenging to reconstruct. A forehead flap may provide a more imperceptible and natural-appearing reconstructed nasal ala. Previously, many authors have insisted adding cartilaginous infrastructural support for an entire, full-thickness defect to keep the postoperative alar structure symmetrical. They finally use a forehead flap after thinning of the distal covering portion subcutaneously, possibly for a Caucasian-type nasal ala. However, Asian skin has a thicker and more compact dermis than that of Caucasian skin, and the Asian ala is rounder and thicker. There may be another approach for an Asian-type nasal ala. The authors propose the possibility of nasal alar reconstruction for an entire, full-thickness defect in Asians using a forehead flap without structural support. Six patients with entire full-thickness nasal alar defects treated with full-thickness forehead flaps above the periosteum without structural support were reviewed. Five patients demonstrated esthetically good to excellent outcomes in color, texture, and symmetry. Their nasal linings were reconstructed using mucoperiosteal flaps or mucosal grafts. One patient treated with a nasal lining using a local flap showed a fair result esthetically. Asians forehead above the periosteum has adequate thickness and supportability to reconstruct the entire full-thickness nasal ala in Asians. No cartilage support is necessary.

Establishment of an Acquired Lymphedema Model in the Mouse Hindlimb: Technical Refinement and Molecular Characteristics
Daisuke Iwasaki, Yuhei Yamamoto, Naoki Murao, Akihiko Oyama, Emi Funayama, Hiroshi Furukawa
PLASTIC AND RECONSTRUCTIVE SURGERY, 139, 1, 67E, 78E, LIPPINCOTT WILLIAMS & WILKINS, 2017年01月, ［査読有り］
英語, 研究論文（学術雑誌）, Background: The pathophysiology of secondary lymphedema remains poorly understood. This study aimed to establish a consistent mouse hindlimb lymphedema model for further investigation of the mechanism and treatment of lymphedema.
Methods: The authors developed a novel postsurgical lymphedema model in the mouse hindlimb by modifying previously described methods. Lymphedema in the hindlimb was created by removing both the inguinal and popliteal lymph nodes together with the surrounding fat pads, followed by silicone splint placement in the inguinal region. Using this modified mouse model, the authors analyzed lymphatic function, histologic changes, and the expression of lymphangiogenic factors including vascular endothelial growth factor C at various time points.
Results: The splinted lymphedema model showed a significant increase of edema formation in the hindlimb compared with the sham surgery control animals. Indocyanine green lymphography revealed lymphatic drainage impairment shown by dermal backflow and rerouting of lymph flow in the lymphedema model. Histopathologic and immunohistochemical examinations showed a significant increase of skin thickness and abnormally dilated lymphatics in the lymphedema model. The expression of lymphangiogenic factors in lymphedematous tissues of the splinted lymphedema model was significantly increased compared with controls, depending on the degree of lymphedema.
Conclusions: This splinted lymphedema model closely simulates the volume response, histopathology, and lymphography characteristics of human acquired lymphedema. Given these similarities to human lymphedema, this refinement of a mouse hindlimb model of acquired lymphedema represents a promising platform for the study of lymphatic vascular insufficiency and for the evaluation of new therapeutic modalities.

3つのコンセプトを融合した片側唇裂口唇形成術の改良法 "ASSIST" technique　　　　　　　　　　　　　　　
小山 明彦, 舟山 恵美, 古川 洋志, 林 利彦, 村尾 尚規, 七戸 龍司, 山本 有平
日本頭蓋顎顔面外科学会誌, 32, 3, 182, 182, (一社)日本頭蓋顎顔面外科学会, 2016年10月
日本語

初回口蓋形成術後の言語成績の比較検討 非症候群性Pierre Robin Sequence VS非症候群性口蓋裂　　　　　　　　　　　　　　　
前田 拓, 舟山 恵美, 小山 明彦, 古川 洋志, 林 利彦, 村尾 尚規, 七戸 龍司, 山本 有平
日本頭蓋顎顔面外科学会誌, 32, 3, 183, 183, (一社)日本頭蓋顎顔面外科学会, 2016年10月
日本語

広範な先天性頭皮頭蓋骨欠損の治療経験 保存的治療か外科的治療か　　　　　　　　　　　　　　　
前田 拓, 小山 明彦, 舟山 恵美, 古川 洋志, 林 利彦, 村尾 尚規, 七戸 龍司, 山本 有平
日本頭蓋顎顔面外科学会誌, 32, 3, 216, 216, (一社)日本頭蓋顎顔面外科学会, 2016年10月
日本語

Reconstruction of Large Cheek Defect With/Without Sideburn Using Malar-Posterior Auricular-Cervico Flap
Toshihiko Hayashi, Yuhei Yamamoto, Akihiko Oyama, Emi Funayama, Ryuji Shichinohe, Naoki Murao, Hiroshi Furukawa
ANNALS OF PLASTIC SURGERY, 77, 2, 173, 177, LIPPINCOTT WILLIAMS & WILKINS, 2016年08月, ［査読有り］
英語, 研究論文（学術雑誌）, The cheek region is the most common site for malignant tumor occurrence and the treatment of malignant skin tumor requires extensive local excision. Many previous reports have covered methods of reconstruction using local flaps for skin defects in the cheek region.
In this article, we describe our experience with a surgical reconstruction using a new flap method for 8 patients with missing tissue in the cheek region. This flap is based on the concept of separately designing the flap with the 3 areas comprising the malar, posterior auricular, and cervical regions. We named the flap containing these 3 regions the malar-posterior auricular-cervico flap. Esthetically satisfactory outcomes were achieved in all cases.
In conclusion, we recommend our malar-posterior auricular-cervico flap to reconstruct the tissue defects of approximately 20 to 40 cm(2) after tumor excision in the cheek region. If preauricular skin is included in the design of this flap, the sideburn can be reconstructed using a part of the nape region with hair.

Exploration of more effective neurorrhaphy in facial nerve reconstruction: A comparison focusing on the difference of neural window size and condition of the neurorrhaphy site
Kentaro Ono, Yuhei Yamamoto, Ryuji Shichinohe, Naoki Murao, Akihiko Oyama, Emi Funayama, Hiroshi Furukawa
JOURNAL OF PLASTIC RECONSTRUCTIVE AND AESTHETIC SURGERY, 69, 8, 1072, 1079, ELSEVIER SCI LTD, 2016年08月, ［査読有り］
英語, 研究論文（学術雑誌）, Background and aim: Various techniques have been introduced for reconstruction of the facial nerve. An improved method of neurorrhaphy to achieve satisfactory mimetic muscle function is required. We made and compared three different neurorrhaphy models to elucidate the effect of neural window size and condition of the neurorrhaphy site on axonal regeneration.
Methods: Rats were divided into four groups: group A, untreated incomplete palsy; group B, treatment by end-to-side neurorrhaphy through a small perineural window; group C, treatment by side-to-side neurorrhaphy through a large perineural window; and group D, treatment by side-to-side neurorrhaphy through a small perineural window. After surgery, mimetic muscle movement was evaluated. Retrograde-labeled neurons through the facial nuclei were counted, and mimetic muscle specimens were examined. The axon number was counted in nerve specimens.
Results: The facial palsy scores of groups B and C were significantly greater than those of groups A and D. With regard to the number of neurons at the facial nuclei, groups B and C had more neurons than groups A and D. Group D had significantly more neurons than group A. With respect to the number of axons, groups B, C, and D had significantly greater numbers than group A, but there were no significant differences between the reconstructed groups.
Conclusions: Window size and condition of the neurorrhaphy site, which affected mainly the number of axons, influenced axonal regeneration in nerve reconstruction. This result indicates the possibility of obtaining a better result for facial nerve or other peripheral nerve reconstruction with a tidbit of operative artifice. (C) 2016 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

当院における過去5年間の児童虐待の実態と形成外科の役割　　　　　　　　　　　　　　　
高橋 紀久子, 舟山 恵美, 本田 進, 北條 正洋, 木村 中
日本形成外科学会会誌, 36, 7, 304, 310, (一社)日本形成外科学会, 2016年07月
日本語, 当院における児童虐待の実態を明らかにすべく、2010年度から2015年度までの5年間に当院の児童虐待防止委員会に連絡のあった423例を対象とし、診療記録から、傷病の種類、診療科、対応手順などを調査した。委員会への連絡件数は年々増加傾向にあり、423例中、予防的介入依頼が397例(94%)で被虐待児の報告は26例(6%)であった。26例の傷病の内訳は体幹・四肢の外傷(8例)、熱傷(7例)、頭部外傷(7例)が多かった。治療にあたった診療科は形成外科が11例と最も多く、医療機関において形成外科は身体的虐待の早期発見のgatekeeperの役割になり得ることが示唆された。形成外科医師は、児童虐待に関する正しい知識を身につけ、多職種連携のもと児童虐待に対応していく責任があると考えられた。(著者抄録)

Reconstruction of low hairline microtia of Treacher Collins syndrome with a hinged mastoid fascial flap
T. Maeda, A. Oyama, E. Funayama, Y. Yamamoto
INTERNATIONAL JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY, 45, 6, 731, 734, CHURCHILL LIVINGSTONE, 2016年06月, ［査読有り］
英語, 研究論文（学術雑誌）, Treacher Collins syndrome (TCS) is a rare genetic disorder leading to congenital craniofacial malfoiniations. Although this syndrome presents with various symptoms, corrective surgery for bilateral microtia with low hairline is one of the most challenging operations given the complex contours of the external ear. In this technical note, a novel, simple procedure for dealing with the low hairline by using a hinged mastoid fascial flap simultaneously with costal cartilage grafting is described. Several techniques for the reconstruction of low hairline microtia have been reported previously, such as skin graft, skin flap, and tissue expander, but the high number of repeat operations and residual scars remain problematic. As a simultaneous procedure with framework grafting, the use of a temporoparietal flap with skin grafting is popular; however, its drawbacks include the operative scar, decreased hair growth, and hair thinning Patients with TCS show anatomical variations of the superficial temporal vessels supplying the temporoparietal flap. In contrast, due to the high vascularity of the mastoid fascia, the mastoid fascial flap can be elevated safely and easily as an anteriorly, posteriorly, superiorly, or inferiorly based flap.

初回口蓋形成術後の鼻咽腔閉鎖不全と二次修正術について 非症候性Pierre Robin Sequenceと非症候性口蓋裂　　　　　　　　　　　　　　　
前田 拓, 舟山 恵美, 小山 明彦, 古川 洋志, 林 利彦, 村尾 尚規, 七戸 龍司, 山本 有平
日本口蓋裂学会雑誌, 41, 2, 104, 104, (一社)日本口蓋裂学会, 2016年04月
日本語

Prevention of Lymphedematous Change in the Mouse Hindlimb by Nonvascularized Lymph Node Transplantation
Ryuta Shioya, Hiroshi Furukawa, Naoki Murao, Toshihiko Hayashi, Akihiko Oyama, Emi Funayama, Yuhei Yamamoto, Noriko Saito
ANNALS OF PLASTIC SURGERY, 76, 4, 442, 445, LIPPINCOTT WILLIAMS & WILKINS, 2016年04月, ［査読有り］
英語, 研究論文（学術雑誌）, Lymphedema is a condition characterized by progressive swelling and adipose deposition that occurs commonly after lymphadenectomy. Recent clinical studies have suggested that the transfer of lymph nodes to the lymphedematous limb can improve lymphatic function. In this report, we investigate dynamic modulation of lymphatic flow and the microscopic changes of lymphatic regeneration using a lymphedema mouse model that was treated with nonvascularized lymph node transplantation. To evaluate the effect of lymph node transplantation in this model, paw volume was measured using a water displacement plethysmometer; an indocyanine green fluorescence-sensitive camera system was used. The improvement of edema was evident in the paw of the transplantation group. The abnormal fluorescence image pattern gradually improved and disappeared 4 weeks postoperatively in the transplantation group. Uptake in the transplanted lymph node was observed 4 weeks postoperatively. This finding suggested that the transplanted lymph node was engrafted. A collateral pathway was observed in the ventral area 1 week postoperatively. The collateral pathway may have contributed to the early improvement of edema. Our findings suggest that lymph node transplantation can restore lymphatic function. This result has important conceptual implications in the treatment of postsurgical lymphedema.

小耳症耳介形成術後の皮膚潰瘍に対する治療戦略　　　　　　　　　　　　　　　
小山 明彦, 古川 洋志, 舟山 恵美, 林 利彦, 村尾 尚規, 七戸 龍司, 山本 有平
日本形成外科学会会誌, 36, 3, 137, 137, (一社)日本形成外科学会, 2016年03月
日本語

小耳症耳介形成術後の皮膚潰瘍の予防を目的とした高気圧酸素療法の有用性　　　　　　　　　　　　　　　
小山 明彦, 塩谷 隆太, 古川 洋志, 舟山 恵美, 林 利彦, 村尾 尚規, 七戸 龍司, 山本 有平
日本形成外科学会会誌, 36, 3, 138, 138, (一社)日本形成外科学会, 2016年03月
日本語

Neuregulin-1 released by biodegradable gelatin hydrogels can accelerate facial nerve regeneration and functional recovery of traumatic facial nerve palsy
Go Yasui, Yuhei Yamamoto, Ryuji Shichinohe, Emi Funayama, Akihiko Oyama, Toshihiko Hayashi, Hiroshi Furukawa
JOURNAL OF PLASTIC RECONSTRUCTIVE AND AESTHETIC SURGERY, 69, 3, 328, 334, ELSEVIER SCI LTD, 2016年03月, ［査読有り］
英語, 研究論文（学術雑誌）, Background and aim: Neuregulin-1 is an essential axoglial signal required for peripheral nerve development, and evidence that neuregulin-1 is also required for effective nerve repair is growing. In this study, the effects of neuregulin-1-impregnated gelatin hydrogels on nerve regeneration and functional recovery after anastomosis of the facial nerve were investigated in a rat model of traumatic facial nerve paralysis.
Materials and methods: Twenty-four adult male rats underwent complete resection of the facial nerve trunk, followed by end-to-end anastomosis with epineural sutures. The animals were then randomly allocated to one of three treatment groups (eight rats/group): no additional intervention (Group I), single-shot injection of neuregulin-1 into the epineurium of the facial nerve at the suture sites (Group II), or implantation of a hydrogel impregnated with neuregulin-1 at the injury site (Group III). After surgery, mimetic muscle movements were evaluated weekly. Eight weeks after surgery, the mimetic muscles were injected with a neural tracer (1,10-dioctadecyl-3,3,30,30-tetramethylindocarbocyanin perchlorate, DiI). Retrograde-labeled neurons were counted in the facial nuclei, and facial nerve specimens were stained with toluidine blue for histological examination of axon density.
Results: Group III exhibited significantly faster recovery of mimetic muscle function, a higher density of large-diameter axons (>5 mu m) in the facial nerve, and greater numbers of retrogradely labeled neurons in the ipsilateral facial nucleus compared with Groups I and II.
Conclusions: Continuous release of neuregulin-1 from impregnated gelatin hydrogels can accelerate facial nerve regeneration. (C) 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

A new primary cleft lip repair technique tailored for Asian patients that combines three surgical concepts: Comparison with rotation-advancement and straight-line methods
Emi Funayama, Yuhei Yamamoto, Hiroshi Furukawa, Naoki Murao, Ryuji Shichinohe, Toshihiko Hayashi, Akihiko Oyama
JOURNAL OF CRANIO-MAXILLOFACIAL SURGERY, 44, 1, 27, 33, CHURCHILL LIVINGSTONE, 2016年01月, ［査読有り］
英語, 研究論文（学術雑誌）, Various techniques have been described for unilateral cleft lip repair. These may be broadly classified into three types of procedure/concept: the straight-line method (SL; Rose-Thompson effect); rotation -advancement (RA; upper-lip Z-plasty); and the triangular flap method (TA; lower-lip Z-plasty). Based on these procedures, cleft lip repair has evolved in recent decades. The cleft lip repair method in our institution has also undergone several changes. However, we have found that further modifications are needed for Asian patients who have wider philtral dimples and columns than Caucasians, while following the principles of the original techniques mentioned above. Here, we have incorporated the advantages of each procedure and propose a refined hybrid operating technique, seeking a more appropriate procedure for Asian patients. To evaluate our new technique, a comparison study was performed to evaluate RA, SL, and our technique.
We have used our new technique to treat 137 consecutive cleft lip cases of all types and degrees of severity, with or without a cleft palate, since 2009. In the time since we adopted the hybrid technique, we have observed improved esthetics of the repaired lip. Our technique demonstrated higher glance impression average scores than RA/SL. (C) 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

美容外科教育 大学での美容外科教育の現状と課題 北海道大学病院における整容・美容外科の現状と教育の課題　　　　　　　　　　　　　　　
舟山 恵美, 小山 明彦, 古川 洋志, 村尾 尚規, 七戸 龍司, 林 利彦, 山本 有平
日本美容外科学会会報, 37, 4, 137, 137, (一社)日本美容外科学会, 2015年12月
日本語

北海道大学病院における急性期熱傷症例の過去5年間の検討　　　　　　　　　　　　　　　
藤田 宗純, 村尾 尚規, 山尾 健, 七戸 龍司, 林 利彦, 舟山 恵美, 小山 明彦, 古川 洋志, 山本 有平, 丸藤 哲
熱傷, 41, 4, 202, 202, (一社)日本熱傷学会, 2015年11月
日本語

Tessier No.3およびNo.4の合併症例 12年間のフォローアップ　　　　　　　　　　　　　　　
前田 拓, 小山 明彦, 岡本 亨, 舟山 恵美, 古川 洋志, 林 利彦, 村尾 尚規, 七戸 龍司, 山本 有平
日本頭蓋顎顔面外科学会誌, 31, 3, 247, 247, (一社)日本頭蓋顎顔面外科学会, 2015年10月
日本語

Effectiveness of intraoperative indocyanine-green fluorescence angiography during inguinal lymph node dissection for skin cancer to prevent postoperative wound dehiscence
Hiroshi Furukawa, Toshihiko Hayashi, Akihiko Oyama, Emi Funayama, Naoki Murao, Takeshi Yamao, Yuhei Yamamoto
SURGERY TODAY, 45, 8, 973, 978, SPRINGER, 2015年08月, ［査読有り］
英語, 研究論文（学術雑誌）, Purpose The incidence of postoperative wound dehiscence following inguinal lymph node dissection (ILND) is higher than that in other anatomic regions. To prevent wound dehiscence, intraoperative interventions, such as trimming off the ischemic part of the flap before wound closure based on indocyanine-green (ICG) fluorescence angiography, have been introduced in our institute. This report describes a retrospective clinical study of 17 cases, and the objective of the study was to evaluate the clinical efficacy of intraoperative intervention using ICG fluorescence angiography.
Method A total of 17 patients who underwent ILND for skin cancer between 2009 and 2013 at our institute were reviewed retrospectively, and the significance of variables, including intervention using ICG fluorescence angiography, was evaluated using Fisher's exact test.
Results There were nine cases of wound dehiscence, and two of these cases required a secondary skin graft. Only one case of wound dehiscence developed in the eight patients who underwent intervention based on ICG fluorescence angiography. This procedure was a significant factor influencing the risk of wound dehiscence (p = 0.003) in our study.
Conclusion Although this was a small case series, intraoperative intervention based on ICG fluorescence angiography was effective for preventing postoperative wound dehiscence after ILND.

北海道大学病院における広範囲熱傷の治療戦略 形成外科医の立場から　　　　　　　　　　　　　　　
藤田 宗純, 村尾 尚規, 七戸 龍司, 林 利彦, 舟山 恵美, 小山 明彦, 古川 洋志, 山本 有平, 宮本 大輔, 丸藤 哲
熱傷, 41, 2, 99, 99, (一社)日本熱傷学会, 2015年06月
日本語

上眼瞼全層欠損に対する余剰皮膚を利用したadvancement flapによる再建　　　　　　　　　　　　　　　
林 利彦, 古川 洋志, 七戸 龍司, 村尾 尚規, 小山 明彦, 舟山 恵美, 山本 有平
頭頸部癌, 41, 2, 215, 215, (一社)日本頭頸部癌学会, 2015年05月
日本語

Dental Arch Relationship Outcomes in One- and Two-Stage Palatoplasty for Japanese Patients With Complete Unilateral Cleft Lip and Palate
Tadashi Mikoya, Toyoko Shibukawa, Takafumi Susami, Yoshiaki Sato, Toshimoto Tengan, Hirotaka Katashima, Akihiko Oyama, Yusuke Matsuzawa, Yumi Ito, Emi Funayama
CLEFT PALATE-CRANIOFACIAL JOURNAL, 52, 3, 277, 286, ALLIANCE COMMUNICATIONS GROUP DIVISION ALLEN PRESS, 2015年05月, ［査読有り］
英語, 研究論文（学術雑誌）, Objective: To compare dental arch relationship outcomes following one-and two-stage palatal repair.
Design: Nonrandomized, clinical trial with concurrent control.
Setting: Hokkaido University Hospital.
Patients: Sixty-eight consecutively treated Japanese patients with complete unilateral cleft lip and palate.
Interventions: Thirty-one of the 68 patients underwent two-stage palatoplasty with delayed hard palate closure, and 37 patients underwent one-stage pushback palatoplasty.
Main Outcome Measures: Dental casts were taken at 4.9 to 6.3 (mean: 5.2) years of age in the two-stage group and at 4.0 to 6.3 (mean: 5.1) years of age in the one-stage group, and dental arch relationships were assessed using the 5-Year-Olds' Index (5-Y) by four raters and the Huddart/Bodenham Index (HB) by two raters.
Results: Intrarater and interrater reliabilities evaluated using weighted kappa statistics were good or better for the 5-Y and HB ratings. The mean 5-Y score was 2.94 in the two-stage group and 3.13 in the one-stage group (P value was not significant). However, there was a significant difference in distributions between the groups (P < .05). The HB scores of molars were significantly greater in the two-stage group than in the one-stage group (P < .05). The rank correlation coefficients between the 5-Y and total HB score (rho = -0.840, P < .01) and between the 5-Y and the score of the incisors in the HB (rho = -0.814, P < .01) were significantly increased.
Conclusions: These results suggest that the anteroposterior relationship was not significantly different between the groups, but the transversal relationship was better in the two-stage group than in the one-stage group.

Successful Conservative Management of a Large Congenital Scalp and Skull Defect
Taku Maeda, Akihiko Oyama, Emi Funayama, Hiroshi Furukawa, Kazutoshi Cho, Yuhei Yamamoto
JOURNAL OF CRANIOFACIAL SURGERY, 26, 3, E275, E277, LIPPINCOTT WILLIAMS & WILKINS, 2015年05月, ［査読有り］
英語, 研究論文（学術雑誌）, The authors report a case of a female baby born with large congenital scalp and skull defects with exposure of the cranial arachnoid mater.
The female patient was delivered by Caesarean section following diagnosis of a large cranial skin defect by ultrasound. The skin defect was present at the time of birth, measured 8.5 cm x 8.0 cm, and involved the full thickness of the cranium. The cranial arachnoid mater was exposed and veins running on the surface of the brain were observed.
There was no means to cover the large defect surgically and conservative treatment was initiated. Complete epithelialization of the scalp defect was acquired without fatal problems. In the course of treatment, Mepilex Transfer was very effective.
The repair of congenital defects of the scalp and skull is a major challenge not only because of the rarity but also because of severe morbidity. A surgical or conservative approach is chosen according to the situation. This rare case highlights two important clinical issues: that the congenital defects of the scalp and skull could not be managed with a surgical approach and in its place, a conservative approach using the special dressing Mepilex Transfer proved highly effective.

Dental arch relationship outcomes in one- and two-stage palatoplasty for Japanese patients with complete unilateral cleft lip and palate
Tadashi Mikoya, Toyoko Shibukawa, Takafumi Susami, Yoshiaki Sato, Toshimoto Tengan, Hirotaka Katashima, Akihiko Oyama, Yusuke Matsuzawa, Yumi Ito, Emi Funayama
Cleft Palate-Craniofacial Journal, 52, 3, 277, 286, American Cleft Palate Craniofacial Association, 2015年05月01日, ［査読有り］
英語, 研究論文（学術雑誌）, Objective: To compare dental arch relationship outcomes following one- and two-stage palatal repair. Design: Nonrandomized, clinical trial with concurrent control. Setting: Hokkaido University Hospital. Patients: Sixty-eight consecutively treated Japanese patients with complete unilateral cleft lip and palate. Interventions: Thirty-one of the 68 patients underwent two-stage palatoplasty with delayed hard palate closure, and 37 patients underwent one-stage pushback palatoplasty. Main Outcome Measures: Dental casts were taken at 4.9 to 6.3 (mean: 5.2) years of age in the two-stage group and at 4.0 to 6.3 (mean: 5.1) years of age in the one-stage group, and dental arch relationships were assessed using the 5-Year-Olds' Index (5-Y) by four raters and the Huddart/ Bodenham Index (HB) by two raters. Results: Intrarater and interrater reliabilities evaluated using weighted kappa statistics were good or better for the 5-Y and HB ratings. The mean 5-Y score was 2.94 in the two-stage group and 3.13 in the one-stage group (P value was not significant). However, there was a significant difference in distributions between the groups (P <
.05). The HB scores of molars were significantly greater in the two-stage group than in the one-stage group (P <
.05). The rank correlation coefficients between the 5-Y and total HB score (ρ = -0.840, P <
.01) and between the 5-Y and the score of the incisors in the HB (ρ = -0.814, P <
.01) were significantly increased. Conclusions: These results suggest that the anteroposterior relationship was not significantly different between the groups, but the transversal relationship was better in the two-stage group than in the one-stage group.

片側性唇顎口蓋裂の術前顎矯正および一期手術 術前・術後の歯槽形態の変化について　　　　　　　　　　　　　　　
岡本 亨, 小山 明彦, 舟山 恵美, 古川 洋志, 林 利彦, 村尾 尚規, 七戸 龍司, 山本 有平
日本口蓋裂学会雑誌, 40, 2, 111, 111, (一社)日本口蓋裂学会, 2015年04月
日本語

A case of combined soft tissue and intraosseous venous malformation of the thumb treated with sclerotherapy using a bone marrow aspiration needle.
Ishikawa K, Sasaki S, Furukawa H, Nagao M, Iwasaki D, Fujita M, Saito N, Oyama A, Yamamoto Y
Case reports in plastic surgery & hand surgery, 2, 2, 37, 39, Informa UK Limited, 2015年, ［査読有り］
研究論文（学術雑誌）

Combined therapy of NPWT and bipedicled flap as an alternative approach for giant abdominal wall defect with significant visceral edema: report of a case.
Yasui G, Furukawa H, Warabi T, Hayashi T, Oyama A, Funayama E, Yamamoto Y
Case reports in plastic surgery & hand surgery, 2, 2, 25, 28, 2015年, ［査読有り］

下顎再建後のプレート露出に対するVAC治療システムおよび高気圧酸素療法を用いた集学的治療　　　　　　　　　　　　　　　
前田 拓, 林 利彦, 古川 洋志, 七戸 龍司, 栗林 和代, 小野 貢伸, 村尾 尚規, 小山 明彦, 舟山 恵美, 山本 有平
日本マイクロサージャリー学会学術集会プログラム・抄録集, 41回, 166, 166, (一社)日本マイクロサージャリー学会, 2014年12月
日本語

Important points for primary cleft palate repair for speech derived from speech outcome after three different types of palatoplasty
Emi Funayama, Yuhei Yamamoto, Noriko Nishizawa, Tadashi Mikoya, Toru Okamoto, Satoko Imai, Naoki Murao, Hiroshi Furukawa, Toshihiko Hayashi, Akihiko Oyama
INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY, 78, 12, 2127, 2131, ELSEVIER IRELAND LTD, 2014年12月, ［査読有り］
英語, 研究論文（学術雑誌）, Objective: This study was performed to investigate speech outcomes after three different types of palatoplasty for the same cleft type. The objective of this study was to investigate the surgical techniques that are essential for normal speech on the basis of each surgical characteristic.
Methods: Thirty-eight consecutive nonsyndromic patients with unilateral complete cleft of the lip, alveolus, and palate were enrolled in this study. Speech outcomes, i.e., nasal emission, velopharyngeal insufficiency, and malarticulation after one-stage pushback (PB), one-stage modified Furlow (MF), or conventional two-stage MF palatoplasty, were evaluated at 4 (before intensive speech therapy) and 8 (after closure of oronasal fistula/unclosed hard palate) years of age.
Results: Velopharyngeal insufficiency at 4 (and 8) years of age was present in 5.9% (0.0%), 0.0% (0.0%), and 10.0% (10.0%) of patients who underwent one-stage PB, one-stage MF, or two-stage MF palatoplasty, respectively. No significant differences in velopharyngeal function were found among these three groups at 4 and 8 years of age. Malarticulation at 4 years of age was found in 35.3%, 10.0%, and 63.6% of patients who underwent one-stage PB, one-stage MF, and two-stage MF palatoplasty, respectively. Malarticulation at 4 years of age was significantly related to the presence of a fistula/unclosed hard palate (P < 0.01). One-stage MF palatoplasty that was not associated with postoperative oronasal fistula (ONF) showed significantly better results than two-stage MF (P < 0.01). Although the incidences of malarticulation at 8 years of age were decreased in each group compared to at 4 years of age, the incidence was still high in patients treated with two-stage MF (45.5%). On the whole, there was a significant correlation between ONF/unclosed hard palate at 4 years of age and malarticulation at 8 years of age (P < 0.05).
Conclusion: Appropriate muscle sling formation can compensate for a lack of retropositioning of the palate for adequate velopharyngeal closure. Early closure of the whole palate and the absence of a palatal fistula were confirmed to be essential for normal speech. To avoid fistula formation, multilayer repair of the whole palate may be critical. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

Combination of Tessier clefts 3 and 4: Case report of a rare anomaly with 12 years' follow-up
Taku Maeda, Akihiko Oyama, Toru Okamoto, Emi Funayama, Hiroshi Furukawa, Toshihiko Hayashi, Naoki Murao, Yoshiaki Sato, Yuhei Yamamoto
JOURNAL OF CRANIO-MAXILLOFACIAL SURGERY, 42, 8, 1985, 1989, CHURCHILL LIVINGSTONE, 2014年12月, ［査読有り］
英語, 研究論文（学術雑誌）, Tessier cleft types 3 and 4 are both rare craniofacial anomalies. Here we present the first case of a girl born with a combined anomaly of Tessier clefts 3 and 4 with severe bilateral cleft lip, a displaced premaxilla, and three-dimensional underdevelopment of the hard and soft tissues of the maxilla and zygoma. This type of rare facial cleft poses a major operative challenge. Over a period of years, presurgical alveolar molding with an active appliance was followed by seven operations. A satisfactory esthetic outcome was obtained. A multidisciplinary approach to treatment with a plastic surgeon in charge of the operations and an orthodontist in charge of the cleft deformity is essential. (C) 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Treg-enriched CD4+T cells attenuate collagen synthesis in keloid fibroblasts
Naoki Murao, Ken-ichiro Seino, Toshihiko Hayashi, Masaki Ikeda, Emi Funayama, Hiroshi Furukawa, Yuhei Yamamoto, Akihiko Oyama
EXPERIMENTAL DERMATOLOGY, 23, 4, 266, 271, WILEY-BLACKWELL, 2014年04月, ［査読有り］
英語, 研究論文（学術雑誌）, Keloid is an inflammatory and fibrotic disease with an unknown pathogenesis. Regulatory T cells (Tregs) of CD4+ lineage can suppress other effector CD4+ T cells and modulate the immune response. A relative decrease in the number of Tregs may be involved in the pathogenesis of inflammatory and fibrotic diseases. We therefore investigated the number of Tregs in keloids using immunohistochemistry and examined the interaction between Tregs and keloid fibroblasts (KFs) using a coculture system. It was found that the ratio of Tregs/CD4+ T cells was lower compared with that in other common inflammatory skin conditions. In addition, Treg-enriched CD4+ T cells reduced collagen synthesis by KFs. Our findings suggest that a local imbalance of Tregs contributes to the development of keloids and that correction of this imbalance might represent a novel therapeutic approach to keloid fibrosis.

An Analysis of Cheek Reconstruction After Tumor Excision in Patients With Melanoma
Toshihiko Hayashi, Hiroshi Furukawa, Akihiko Oyama, Emi Funayama, Akira Saito, Yuhei Yamamoto
JOURNAL OF CRANIOFACIAL SURGERY, 25, 2, E98, E101, LIPPINCOTT WILLIAMS & WILKINS, 2014年03月, ［査読有り］
英語, 研究論文（学術雑誌）, Background The most common site for melanoma occurrence is the cheek region, and the treatment of melanoma requires extensive local excision. This study evaluated factors that influence the selection of reconstructive procedures after excision of a cheek melanoma.
Methods A total of 26 cases (12 with skin grafts, 7 with local flaps, and 7 with free flaps) were included in the study. Factors in the selection of reconstructive procedures were evaluated by examining the size of the skin defects, patient age, and prognosis.
Results Free flaps were frequently used in cases with large areas of skin defect and with thicker melanomas. Skin grafts were used for a wide variety of tumor thicknesses and for older patients with thick melanomas (due to the general condition of the patients). The dividing line of the range of skin defects between local and free flaps was approximately 40 cm(2). Reconstruction procedures had no impact on prognosis.
Conclusions In deciding on a reconstruction procedure after the excision of a cheek melanoma, 3 factors are important: the range of the skin defect, the severity of the melanoma, and the age of the patient.

Dominant lymph drainage in the upper extremity and upper trunk region: evaluation of lymph drainage in patients with skin melanomas
Toshihiko Hayashi, Hiroshi Furukawa, Akihiko Oyama, Emi Funayama, Akira Saito, Yuhei Yamamoto
INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY, 19, 1, 193, 197, SPRINGER JAPAN KK, 2014年02月, ［査読有り］
英語, 研究論文（学術雑誌）, Background The objective of this study is to evaluate the lymph drainage from the primary focus to the regional lymph nodes in patients with melanomas of the upper extremity and upper trunk region.
Method The study is a retrospective study of 20 patients with upper extremity melanomas and 14 patients with upper trunk melanomas treated with axillary lymph node dissection (ALND) or sentinel lymph node biopsy at the hospital. ALND was performed in 14 cases. In these cases, 12 were curative dissections and 2 were elective dissections. The dominant lymph drainage patterns from the primary regions were analyzed.
Results Among the upper extremity and upper trunk region melanomas, lymph drainage to Level I was determined in all cases. In these two regions there were no cases of lymph drainage to Level II not passing through Level I. Furthermore, there were no cases where sentinel lymph node or metastasis of the lymph nodes was clearly determined in Level III. Among the upper extremity melanomas, lymph drainages to the cubital (10 %) and mid-arm nodes (5 %) were established. Among the scapular region melanomas, lymph drainages to the supraclavicular nodes (25 %) were determined.
Conclusions There was a dominant lymph drainage pattern of melanomas of the upper extremity and upper trunk region to Level I. No lymph node dissection of Level III in patients with melanomas of the upper extremity and upper trunk region is necessary unless preoperative examination determines a high possibility of metastasis-positive lymph nodes in level III.

Minor-Form/Microform Cleft Lip Repair The Importance of Identification and Utilization of Cupid Bow Peak on the Lateral Lip
Akihiko Oyama, Emi Funayama, Hiroshi Furukawa, Toshihiko Hayashi, Akira Saito, Yuhei Yamamoto
ANNALS OF PLASTIC SURGERY, 72, 1, 47, 49, LIPPINCOTT WILLIAMS & WILKINS, 2014年01月, ［査読有り］
英語, 研究論文（学術雑誌）, In minor-form or microform cleft lip, normal anatomical structures with slight displacement remain and should be used effectively to obtain symmetrical results.
We treated 7 patients with minor-form or microform cleft lip between 2005 and 2009. In all patients, the peak of Cupid bow with a natural curve of the white roll was recognized on the lateral lip. We modified the incision line to maintain the natural curve and obtained a symmetrical and natural-looking Cupid bow.
In this article, we emphasize the importance of preserving the remaining normal structure, particularly the curve of the white roll on the lateral lip, and suggest that the peak of the curve should be defined as Cupid bow peak of the cleft side. Details of our concept for the correction of minor-form or microform cleft lip are also introduced.

Flap reconstruction in two patients with rare blood coagulation disorders
Toshihiko Hayashi, Akira Saito, Hiroshi Furukawa, Akihiko Oyama, Emi Funayama, Yuhei Yamamoto
European Journal of Plastic Surgery, 37, 5, 297, 300, Springer Verlag, 2014年, ［査読有り］
英語, 研究論文（学術雑誌）, Coagulation disorders can be classified into two types: excessive bleeding and excessive clotting. Furthermore, the severity of the coagulation disorders can vary significantly among patients. We evaluated two relatively rare cases involving factor XIII subunit deficiency and antiphospholipid syndrome (APS) with concomitant systemic lupus erythematosus (SLE) in two patients undergoing flap reconstructions after tumor excision. In the patient with excessive bleeding as a result of a factor XIII subunit deficiency, flap necrosis occurred from a large subcutaneous hematoma that pressed on the perforator pedicle. Normal clotting function was restored during the surgery by administering a factor XIII preparation (Fibrogammin® P). The patient with excessive clotting as a result of APS and SLE suffered necrosis of the flaps after undergoing radial forearm free flap (RFFF) and pedicled pectoralis major musculocutaneous (PMMC) flap operations. With clotting factor deficiencies, there are patients in whom no evidence of a coagulation disorder exists preoperatively. It is important for surgeons to pay close attention to the potential for coagulation disorders patients and to consult with specialists promptly when indicated. Level of Evidence: Level V, risk/prognostic study. © 2014 Springer-Verlag.

Skin necrosis around bilateral buttock of hikikomori teenager
Hiroshi Furukawa, Akihiko Oyama, Emi Funayama, Toshihiko Hayashi, Yuhei Yamamoto
International Journal of Culture and Mental Health, 7, 1, 43, 45, 2014年, ［査読有り］
英語, 研究論文（学術雑誌）, Hikikomori, or severe social withdrawal, in Japan's young people has been a prominent public mental health concern since around 2000. A case of skin necrosis in a hikikomori teenager is reported in this article. From the patient's history and the shape of the skin ulcer, we diagnosed her necrotic ulcer was pressure sore, caused by sitting on the toilet seat for a long time. Antibiotic treatment, surgical debridement and skin were performed. The ulcer was healed eight weeks after admission. In future, the incidence that medical staff, not psychiatrists, encounters in hikikomori patients may increase because of the increase of the secondary disease based on hikikomori. The consensus about the causes, diagnosis and therapeutic interventions for hikikomori will be required not only by psychiatrists but also by all of the medical staff now, with urgency. © 2012 Taylor &
Francis.

遊離腓骨皮弁で再建した下顎骨粘液腫の1例　　　　　　　　　　　　　　　
佐藤 千草, 坂本 泰輔, 蕨 雄大, 舟山 恵美, 山本 有平
日本形成外科学会会誌, 33, 11, 835, 840, (一社)日本形成外科学会, 2013年11月
日本語, 22歳男。主訴は右下顎部の違和感であった。齲歯治療の際、X線写真で下顎骨体部からオトガイ部の透過像と下顎の左3番〜右4番の歯軸の乱れを指摘された。CTでは同部の骨内に腫瘍性病変と下顎骨における皮質骨の菲薄化および骨破壊像を認め、MRIではT1強調像で高信号を呈する内部がやや不均一な腫瘤により下顎骨が占拠されていた。生検の病理組織検査の結果下顎骨粘液腫と診断され、左4番〜右6番で歯槽・歯肉を含めた下顎骨区域切除と遊離腓骨皮弁による再建を施行した。術後、骨付き皮弁は完全生着し、5年経過して再発は認めず、義歯を使用して普通食の摂取も可能である。

Preliminary experience with intraoperative near-infrared fluorescence imaging in percutaneous sclerotherapy of soft-tissue venous malformations
Ishikawa, K., Sasaki, S., Furukawa, H., Nagao, M., Iwasaki, D., Saito, N., Yamamoto, Y.
Dermatologic Surgery, 39, 6, 907, 912, Ovid Technologies (Wolters Kluwer Health), 2013年06月01日, ［査読有り］
英語, 研究論文（学術雑誌）

Efficacy of percutaneous ethanol sclerotherapy for venous malformation in lower extremities: A retrospective review of 21 cases
Hiroshi Furukawa, Satoru Sasaki, Akihiko Oyama, Emi Funayama, Toshihiko Hayashi, Noriko Saito, Munetomo Nagao, William Mol, Yuhei Yamamoto
European Journal of Plastic Surgery, 36, 2, 105, 110, 2013年02月, ［査読有り］
英語, 研究論文（学術雑誌）, Background: Venous malformations (VM) of lower extremities have characteristic symptoms, especially swelling, pain at rest or with dependence, or in the morning, or with exertion. Sclerotherapy has been applied and has been showed to alleviate the associated signs and symptoms. The aim of this study is to evaluate the outcomes of ethanol sclerotherapy for VM of lower extremities. Methods: The 21 patients of intramuscular VM of the lower extremities, who received percutaneous sclerotherapy using absolute ethanol in our institute, were reviewed retrospectively. The average age at the time of the initial diagnosis was 18.6 years, and average follow-up period after last sclerotherapy is 19.4 ± 13.5 months. The postinterventional changes of the associated signs and symptoms were evaluated by utilizing original VM scoring system. Results: The average number of sclerotherapy sessions was 2.6 times per case. The average total amount of ethanol used in each patient was 41.3 ml. Sclerotherapy reduced the associated signs and symptoms in many of the patients (n = 19/21). Preinterventional VM score as the overall baseline status was 10, and the average VM score after sclerotherapy was 4.1. There was no inverse correlation between the amount of ethanol used and the VM score. In seven cases treated more than three times, reverse correlation between the "VM score" and the number of sclerotherapy sessions was demonstrated (p <
0.05, ρ = 0.8214). Conclusions: The characteristic symptoms and signs of the VM were improved by sclerotherapy. More than three sessions of ethanol sclerotherapy improved the overall status of extensive intramuscular VM in lower extremities. Level of Evidence: Level IV, therapeutic study. © 2012 Springer-Verlag.

A New Aspect of Metastasis in Cutaneous Cancer Two Cases of Presacral Squamous Cell Carcinoma With Metastases to Internal Iliac Nodes
Kohei Oashi, Toshihiko Hayashi, Hiroshi Furukawa, Arata Tsutsumida, Chu Kimura, Hiroshi Oyamatsu, Akihiko Oyama, Emi Funayama, Akira Saito, Yuhei Yamamoto
ANNALS OF PLASTIC SURGERY, 70, 1, 79, 81, LIPPINCOTT WILLIAMS & WILKINS, 2013年01月, ［査読有り］
英語, 研究論文（学術雑誌）, We report 2 cases of presacral squamous cell carcinoma. In these cases, it was suspicious that the tumor disseminated to the internal iliac nodes through the direct pathway called the neurovascular lymphatic space (NVLS) around the superior/inferior gluteal vessels or sciatic nerve bypassing external iliac nodes. NVLS was initially reported as accessory pathway which follows the major vessels forming a sheath like structure with an actual or potential space between the vessel wall and the enveloping membrane. NVLS has been reported to be observed as a tubular shadow within the neurovascular sheath by lymphangiographies of lymphedema patients using oil-based contrast material. These cases provide insights into the potential pathway through which a cutaneous tumor disseminates.

Pathophysiological characteristics of melanoma in-transit metastasis in a lymphedema mouse model
Kohei Oashi, Hiroshi Furukawa, Hiroshi Nishihara, Michitaka Ozaki, Akihiko Oyama, Emi Funayama, Toshihiko Hayashi, Yuji Kuge, Yuhei Yamamoto
Journal of Investigative Dermatology, 133, 2, 537, 544, Nature Publishing Group, 2013年, ［査読有り］
英語, 研究論文（学術雑誌）, In-transit metastasis (ITM) is a unique manifestation of intralymphatic tumor dissemination, characterized by the presence of melanoma cells between the primary lesion and the draining regional lymph node basin that is clinically associated with poor prognosis. In this study, we aimed to establish an experimental animal model of melanoma ITM, as research progress in this field has been hampered by a lack of suitable experimental models. We reproduced melanoma ITM in a mouse hind limb by transplanting melanoma cells into the footpad of a mouse with lymphedema (LE). The tumor cells at the ITM site were highly proliferative, and mice with ITMs were more likely than control mice to develop distant lymph node and lung metastases. Peritumoral lymphatic vessels and tumor-associated blood vessels were increased in the primary tumor site of the LE mice. Our established ITM melanoma mouse model enabled us to clarify the molecular determinants and pathophysiology of ITM. This ITM model is also comparable to the unfavorable clinical behavior of melanoma ITM in humans and, moreover, underlined the importance of lymphangiogenic factors in the tumor dissemination through the lymphatic system. © 2013 The Society for Investigative Dermatology.

皮膚がんに特化した腋窩リンパ節郭清術についての検討
古川 洋志, 林 利彦, 大芦 孝平, 小山 明彦, 舟山 恵美, 山本 有平, 堤田 新, 齋藤 亮, 皆川 英彦, 吉田 哲憲
Skin Cancer, 27, 3, 274, 274, The Japanese Skin Cancer Society, 2013年
日本語

皮膚がん治療における頸部郭清術の工夫
林 利彦, 古川 洋志, 大芦 孝平, 小山 明彦, 舟山 恵美, 山本 有平
Skin Cancer, 27, 3, 268, 268, The Japanese Skin Cancer Society, 2013年
日本語

ICGを併用したnavigation surgery－SLNBおよび腫瘍切除/所属リンパ節郭清に対する新たな取り組み－
林 利彦, 古川 洋志, 大芦 孝平, 小山 明彦, 舟山 恵美, 山本 有平
Skin Cancer, 27, 3, 294, 295, The Japanese Skin Cancer Society, 2013年
日本語

血管腫・血管奇形治療マニュアル 血管腫・血管奇形の保存的対処法
古川洋志, 舟山恵美, 山本有平
PEPARS, 71, 19, 25, 全日本病院出版会, 2012年11月15日
日本語

A New Model of Acquired Lymphedema in the Mouse Hind Limb A Preliminary Report
Kohei Oashi, Hiroshi Furukawa, Akihiko Oyama, Emi Funayama, Toshihiko Hayashi, Akira Saito, Yuhei Yamamoto
ANNALS OF PLASTIC SURGERY, 69, 5, 565, 568, LIPPINCOTT WILLIAMS & WILKINS, 2012年11月, ［査読有り］
英語, 研究論文（学術雑誌）, Lymphedema is known to be caused by many pathologic conditions; however, its correct diagnosis and optimal therapeutic strategies remain to be established. In this report, we describe an experimental model for acquired lymphedema in the lower extremity of the mouse that creates a lymphatic block in the groin induced by both radiation treatment and surgical division of the superficial and deep lymphatics. To evaluate the lymphatic system in this model, an indocyanine green fluorescence-sensitive camera system was used. This model has the advantages of relative technical simplicity and cost-effective use of a rodent animal model. Furthermore, a greater range of research tools such as antibodies and various databases are available for mice. This mouse model may be useful to anyone modeling lymphedema mechanisms, by providing a defined molecular context.

Effectiveness of combined pulsed dye and Q-switched ruby laser treatment for large to giant congenital melanocytic naevi
E. Funayama, S. Sasaki, H. Furukawa, T. Hayashi, T. Yamao, K. Takahashi, Y. Yamamoto, A. Oyama
BRITISH JOURNAL OF DERMATOLOGY, 167, 5, 1085, 1091, WILEY-BLACKWELL, 2012年11月, ［査読有り］
英語, 研究論文（学術雑誌）, Background There is no consensus on the most appropriate treatment for patients with large to giant congenital melanocytic naevi (CMN) because of the risk of melanoma development. Surgical excision followed by skin grafting or expanded skin coverage may cause unfavourable scarring. There is a balance to be achieved between minimizing the disfiguring appearance and the risk of malignant change. The pulsed dye laser (PDL) is commonly used for vascular lesions and is highly absorbed by melanin and haemoglobin. Its pulse duration is longer than that of Q-switched ruby lasers (QsRL), which can have nonspecific photothermolytic effects on surrounding nonpigmented naevus cells.
Objectives To investigate the effectiveness of combined treatment with the PDL and QsRL for large to giant CMN.
Methods Six patients with large to giant CMN were enrolled in this study. Treatment consisted of one pass of PDL treatment followed by one pass of QsRL treatment. Multiple rounds of treatment were applied to all patients.
Results All patients responded to this combined regimen, and the lesional colour was effectively reduced. The mean number of rounds of laser treatment required to achieve skin lightening was 7.7. No patients suffered severe hypertrophic scarring. No cases of recurrence or malignant transformation were observed. The histological results from the patient who underwent the most laser therapy in this study showed a remarkable reduction in the number of melanocytic naevus cells after treatment.
Conclusions This technique may enable the removal of most of the pigmented lesion and melanocytic naevus cells with minimal scarring.

インドシアニングリーン蛍光リンパ管造影による dermal lymphatic back-flow を標的とした, 乳がん術後上肢リンパ浮腫に対するリンパ管静脈移植術
古川, 洋志, 大澤, 昌之, 齋藤, 亮, 林, 利彦, 舟山, 恵美, 小山, 明彦, 関堂, 充, 山本, 有平
北海道醫學雜誌 = Acta medica Hokkaidonensia, 87, 6, 270, 270, 2012年11月
日本語, 研究論文（学術雑誌）

Vascularised fat flaps lose 44% of their weight 24 weeks after transplantation
Kohei Oashi, Hiroshi Furukawa, Sadanori Akita, Masahiro Nakashima, Katsuya Matsuda, Akihiko Oyama, Emi Funayama, Toshihiko Hayashi, Akiyoshi Hirano, Yuhei Yamamoto
JOURNAL OF PLASTIC RECONSTRUCTIVE AND AESTHETIC SURGERY, 65, 10, 1403, 1409, ELSEVIER SCI LTD, 2012年10月, ［査読有り］
英語, 研究論文（学術雑誌）, Background: Microsurgical transfer of the vascularised fat flaps has become a well-established method for soft-tissue augmentation because it has been believed to provide the restoration of symmetry without atrophy. Yet little has been reported on the long-term fate of the vascularised fat flaps. The purpose of this study was to evaluate the post-operative changes that occur in the vascularised fat flaps after transplantation.
Methods: The superficial epigastric fat flaps based on the superficial inferior epigastric vessels in rats were used for this study. Postoperative changes were analysed by comparing pre- and postoperative weight, histological examination and fluorescent angiography.
Results: The weight of vascularised fat flaps was 56 +/- 18% of the original weight (corrected for body weight gain) 24 weeks after transplantation. In histological examinations, the vascularised fat flaps had almost normal appearances throughout the experimental period. Apoptosis of adipocytes was detected in the vascularised fat flaps using terminal deoxynucleotidyl transferase (TdT)-mediated deoxy-uridine triphosphate (dUTP)-biotin nick end-labelling (TUNEL) method during the first 4 weeks after transplantation.
Conclusions: The vascularised fat flaps reduced in weight by about 44% over a period of 24 weeks after transplantation. Apoptosis may partly explain the weight loss.

Dominant lymph drainage in the facial region: evaluation of lymph nodes of facial melanoma patients
Toshihiko Hayashi, Hiroshi Furukawa, Akihiko Oyama, Emi Funayama, Akira Saito, Yuhei Yamamoto
INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY, 17, 4, 330, 335, SPRINGER JAPAN KK, 2012年08月, ［査読有り］
英語, 研究論文（学術雑誌）, The purpose of this study was to evaluate the superficial lymph drainage patterns from primary lesions, with the primary focus on cheek/eyelid and lip melanomas.
We conducted a retrospective study of 22 patients with facial melanomas who had undergone neck dissection or sentinel lymph node biopsy at the hospital from 1981 to April 2011. We then analyzed the dominant lymph drainage patterns from the cheek/eyelid and lip regions.
The cheek/eyelid regions have two lymph drainage patterns: one is to the parotid nodes and the other is to level IB. The lymph drainage patterns in the lip region are to level IA or IB. The lymph drainage patterns to superficial lymph nodes from the primary sites were determined in both regions.
Cheek/eyelid and lip melanomas have lymph drainage patterns different from those of malignant tumors of the oropharyngeal and larynx regions. Superficial lymph node groups also play an important role in facial melanomas.

A New Uniform Protocol of Combined Corticosteroid Injections and Ointment Application Reduces Recurrence Rates After Surgical Keloid/Hypertrophic Scar Excision
Toshihiko Hayashi, Hiroshi Furukawa, Akihiko Oyama, Emi Funayama, Akira Saito, Naoki Murao, Yuhei Yamamoto
DERMATOLOGIC SURGERY, 38, 6, 893, 897, WILEY-BLACKWELL, 2012年06月, ［査読有り］
英語, 研究論文（学術雑誌）, Background Published reports indicate that corticosteroid injections can prevent recurrence after keloid excision, but the side effects of repetitive intralesional steroid injections may preclude treatment maintenance. Additionally, few of these studies employed a standardized treatment protocol. Objectives To analyze the results of a new uniform treatment protocol combining corticosteroid injections and ointment application designed to reduce recurrence rates after excisional surgery in individuals with keloids or hypertrophic scars. Methods As a standard procedure, the first corticosteroid injection took place after removal of the sutures and then once every 2 weeks after that until it had been done five times. In addition, all postsurgical wounds received self-administered steroid ointment application twice daily for 6 months after suture removal. Results Postoperative follow-up in this series ranged from 24 to 57 months (median 32 months, mean 32.5 months). Recurrence occurred in three of the 21 keloid cases (14.3%) and one of the six hypertrophic scar cases (16.7%). Conclusion We evaluated a new standardized adjuvant corticosteroid therapy to prevent recurrence after surgical keloid or hypertrophic scar excision. Using this method, we achieved low recurrence rates.

Direction of innervation after interpositional nerve graft between facial and hypoglossal nerves in individuals with or without facial palsy: A rat model for treating incomplete facial palsy
Ryuji Shichinohe, Hiroshi Furukawa, Mitsuru Sekido, Akira Saito, Toshihiko Hayashi, Emi Funayama, Akihiko Oyama, Yuhei Yamamoto
JOURNAL OF PLASTIC RECONSTRUCTIVE AND AESTHETIC SURGERY, 65, 6, 763, 770, ELSEVIER SCI LTD, 2012年06月, ［査読有り］
英語, 研究論文（学術雑誌）, Background: The use of an interpositional nerve graft (IPNG) between the facial and hypoglossal nerves for incomplete facial palsy has recently been reported. However, its mechanism has not been elucidated. We established a rat model of IPNG to study incomplete facial palsy and confirmed the direction of innervation through the grafted nerve with or without facial nerve injury.
Methods: Twenty rats were divided into five groups (n = 4): a control group (group A), an incomplete facial palsy group (group B), an IPNG-treated group (group C), an incomplete facial palsy group treated with IPNG (group D) and an incomplete hypoglossal nerve palsy group treated with IPNG (group E). After surgery, mimetic muscle movement was evaluated using an original scoring system. Twelve weeks after surgery, the mimetic muscles of the tongue were injected with Fast Blue and DiI. Retrograde-labelled neurons were counted through the facial and hypoglossal nuclei, and mimetic muscle specimens stained with Masson's trichrome were examined.
Results: Fast Blue-labelled neurons were noted in the hypoglossal nucleus in groups C and D, and DiI-labelled neurons within the facial nucleus were noted in groups C and E. The group D facial palsy score statistically exceeded the group B score.
Conclusions: The results revealed that axonal regeneration through IPNG is bi-directional and is preferentially directed towards the injured side. Innervation from the hypoglossal nerve to mimetic muscles through IPNG prevents muscle atrophy and helps counter facial palsy. (C) 2012 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Sentinel lymph node biopsy using real-time fluorescence navigation with indocyanine green in cutaneous head and neck/lip mucosa melanomas
Toshihiko Hayashi, Hiroshi Furukawa, Akihiko Oyama, Emi Funayama, Akira Saito, Takeshi Yamao, Yuhei Yamamoto
HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK, 34, 5, 758, 761, WILEY-BLACKWELL, 2012年05月, ［査読有り］
英語, 研究論文（学術雑誌）, Background The triple technique (lymphoscintigraphy, patent-blue staining, and a gamma probe) constitutes a reliable method for the sentinel lymph node (SLN) biopsy. However, in head and neck melanomas, a shine-through phenomenon, which occurs because these SLNs are close to the primary focus, is irreversibly problematic. To get around the shine-through phenomenon, this study uses the fluorescence navigation with indocyanine green (ICG) as well as the triple technique.
Methods. ICG is a green dye and can be used as a marker with infrared fluorescence. ICG solution is intradermally injected around the tumor. By using Photodynamic Eye ( PDE) intraoperatively, it is possible to observe the injected ICG as SLNs in the fluorescence images.
Results. By use of the fluorescence imaging with ICG, clear identification of the SLN of the case became possible.
Conclusions. We think the fluorescence navigation with ICG will be a useful option for the SLN biopsy in head and neck melanomas. (C) 2011 Wiley Periodicals, Inc. Head Neck 34: 758-761, 2012

Reconstruction of periorbital defects following malignant tumour excision: A report of 50 cases
Akira Saito, Noriko Saito, Hiroshi Furukawa, Toshihiko Hayashi, Akihiko Oyama, Emi Funayama, Hidehiko Minakawa, Yuhei Yamamoto
JOURNAL OF PLASTIC RECONSTRUCTIVE AND AESTHETIC SURGERY, 65, 5, 665, 670, ELSEVIER SCI LTD, 2012年05月, ［査読有り］
英語, 研究論文（学術雑誌）, Background: Treatment in malignant periorbital tumours requires a radical resection of the tumour, and reconstruction of eyelid defects is difficult task because it should aim at gaining functional and aesthetical improvement.
Methods: We have reviewed 50 cases of malignant periorbital tumour that were treated surgically from 1992 to 2010. We assessed the type of reconstruction performed, and present or absent of any complication.
Results: The decision of the appropriate reconstructive procedure was based on the location of the tumour and the size of the defects. For the upper eyelid, switch flap from lower lid was performed in 11 out of 14 patients those defects exceeding 50% of the horizontal length. There were 21 complications (42%); major complications in 11 patients (22%) and minor complications in 10 patients (20%). Major complications have occurred only in upper eyelid or in lower eyelid. All of the major complications appeared in the patients with larger defects exceeding 50%.
Conclusions: The 72% of major complications were associated with reconstruction of larger defects in upper eyelid. It might be extremely difficult to obtain good results in the patients with large upper eyelid defects, although switch flap is applicable to such defects. (C) 2011 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Effectiveness of muscle coverage to manage osteomyelitis of very late onset in the irradiated chest wall
Emi Funayama, Hidehiko Minakawa, Hidekazu Otani, Akihiko Oyama, Hiroshi Furukawa, Toshihiko Hayashi, Noriko Saito, Akira Saito, Yuhei Yamamoto
SURGERY TODAY, 42, 3, 306, 311, SPRINGER, 2012年02月, ［査読有り］
英語, 研究論文（学術雑誌）, Radiation therapy for breast cancer has improved survival rates; however, a consequence of this is treatment-induced complications in longer-living patients. Decades after chest wall irradiation, very late onset radiation-induced osteomyelitis can develop, caused by osteoradionecrosis. This may lead to the development of small, but very refractory, skin ulcers. Many reports recommend well-vascularized tissue coverage after appropriate debridement for irradiation ulcers; however, when the ulcers are of very late onset, this sometimes causes recurrence of ulceration in non-muscle-covered areas after flap transfer. Thus, for very late onset cases, we propose treatment with an absolute muscle flap to cover both the obviously infected focus and the surrounding irradiated area. A muscle flap consisting of the entire latissimus dorsi, the shape of which is very large in the horizontal direction, satisfies this requirement. Latissimus dorsi muscle coverage for the treatment of very late onset osteomyelitis should be reappraised.

北海道がんセンター形成外科における皮膚悪性腫瘍症例の統計
齋藤 亮, 皆川 英彦, 齋藤 典子, 舟山 恵美, 野崎 愛, 高橋 依子, 加藤 直子
Skin Cancer, 27, 2, 137, 142, The Japanese Skin Cancer Society, 2012年
日本語, 2001年から2011年までに，形成外科単独あるいは皮膚科を主とする他科との共同で手術治療を行った皮膚悪性腫瘍症例300例の統計的観察を行った。性別は男143例，女157例，年齢は平均71.5歳であった。年平均症例数は27.2例であり，近年漸減傾向にあった。疾患別頻度では基底細胞癌101例（34％），有棘細胞癌73例（24％）などであった。部位別頻度は頭頸部が64％，上肢10％，下肢14％，体幹8％，外陰部5％であった。当科受診の際に，他科もしくは他院から紹介があった症例は285例（95％）であり，そのうち当院・他院を合わせた皮膚科からの紹介が83％であった。当科が治療に携わった症例数は漸減傾向にあり，当院皮膚科常勤医の減少が主な理由と考えられた。皮膚悪性腫瘍患者が直接，形成外科を受診することは稀であり同施設あるいは他施設皮膚科との協力体制は必要不可欠であると考えられた。

INTRAOPERATIVE COLOR DOPPLER SONOGRAPHY IN THE ELEVATION OF ANTEROLATERAL THIGH FLAP
Akira Saito, Hiroshi Furukawa, Toshihiko Hayashi, Akihiko Oyama, Emi Funayama, Yuhei Yamamoto
MICROSURGERY, 31, 7, 582, 583, WILEY-BLACKWELL, 2011年10月, ［査読有り］
英語

北海道大学における整容・美容外科診療-大学病院の果たす役割
舟山 恵美, 山本 有平, 小山 明彦, 古川 洋志, 林 利彦
日形会誌 : 日本形成外科学会会誌 = Journal of Japan Society of Plastic and Reconstructive Surgery, 31, 9, 619, 627, 2011年09月20日
日本語

PRELIMINARY REPORT OF PREOPERATIVE ASSESSMENT OF ANTEROLATERAL THIGH FLAP PERFORATORS USING REAL-TIME VIRTUAL SONOGRAPHY SYSTEM
Akira Saito, Hiroshi Furukawa, Toshihiko Hayashi, Akihiko Oyama, Emi Funayama, Yuhei Yamamoto
MICROSURGERY, 31, 6, 499, 501, WILEY-BLACKWELL, 2011年09月, ［査読有り］
英語

Ethanol sclerotherapy with 'injection and aspiration technique' for giant lymphatic malformation in adult cases
Hiroshi Furukawa, Satoru Sasaki, Akihiko Oyama, Toshihiko Hayashi, Emi Funayama, Noriko Saito, Yuhei Yamamoto
JOURNAL OF PLASTIC RECONSTRUCTIVE AND AESTHETIC SURGERY, 64, 6, 809, 811, ELSEVIER SCI LTD, 2011年06月, ［査読有り］
英語, 研究論文（学術雑誌）, Ethanol is a commonly used sclerosant for lymphatic malformation (LM), and recent evidence has shown that macrocystic LMs respond very well to percutaneous sclerotherapy. However, the volume of absolute ethanol that can be injected safely is small (0.5-1ml/kg), and that is the reason it is often ineffective in extensive LM. We report two cases of giant LM with occasional high fever and pain or abnormal gait. To overcome dose limitation and to prevent systematic toxicities, we performed both injection of absolute ethanol and aspiration of it after 5 min exposure to LM. The injected maximum ethanol dose per one session is 70-260 ml and no systemic complication occurred. The 1-3 sessions of those procedures reduced the frequency of high fever and improved the swelling of those lesions. The injection and aspiration technique maximises the efficacy of sclerotherapy for extensive macrocystic LM in adults. (C) 2010 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Microsurgical Lymphaticovenous Implantation Targeting Dermal Lymphatic Backflow Using Indocyanine Green Fluorescence Lymphography in the Treatment of Postmastectomy Lymphedema
Hiroshi Furukawa, Masayuki Osawa, Akira Saito, Toshihiko Hayashi, Emi Funayama, Akihiko Oyama, Mitsuru Sekido, Yuhei Yamamoto
PLASTIC AND RECONSTRUCTIVE SURGERY, 127, 5, 1804, 1811, LIPPINCOTT WILLIAMS & WILKINS, 2011年05月, ［査読有り］
英語, 研究論文（学術雑誌）, Background: Microsurgical lymphaticovenous implantation in lymphedema is done to create a lymphaticovenous shunt by an implantation of collecting lymphatics into the small vein, as reported previously. The authors have recently introduced ultrasonograpy and indocyanine green fluorescence lymphography into this procedure.
Methods: Nine cases of postmastectomy lymphedema had received preoperative venous marking using ultrasonography and lymphatic mapping using indocyanine green fluorescence lymphography. The concept of modification is to pick up the most effective point for microsurgical lymphaticovenous implantation that involves both subcutaneous veins and the dermal backflow of excess lymphatics. Objective improvement was analyzed by the percent reduction of edema circumference at two points of the affected forearm.
Results: Preoperative lymphography showed a spotty image for dermal backflow in all nine extremities, a linear image on the dorsal hand in six extremities, and a linear image on the forearm in three extremities. With an average follow-up of 17 months, three patients had excellent results with the reduction of edema circumference more than 50 percent for both the distal and proximal sites of the treated forearm. Four patients had good results with the reduction of edema circumference more than 50 percent at the distal or proximal sites, two patients had fair results, and no patients had poor results. The average number of modified microsurgical lymphaticovenous implantations was 3.7 per case.
Conclusion: Modified microsurgical lymphaticovenous implantation is expected to provide favorable results with aminimum number of these modified implantations, even though no linear lymph channel was detected by preoperative indocyanine green fluorescence lymphography. (Plast. Reconstr. Surg. 127: 1804, 2011.)

小耳症手術において自然な形態を得るための要点 (特集 小耳症--私の手術法)
小山 明彦, 古川 洋志, 舟山 恵美
形成外科, 54, 3, 243, 250, 克誠堂出版, 2011年03月
日本語

How do the type and location of a vascular malformation influence growth in Klippel-Trénaunay syndrome?
Funayama E, Sasaki S, Oyama A, Furukawa H, Hayashi T, Yamamoto Y
Plastic and reconstructive surgery, 127, 1, 340, 346, 1, 2011年01月, ［査読有り］
英語, 研究論文（学術雑誌）, Background: Although Klippel-Trenaunay syndrome is a mixed vascular malformation characterized by abnormal growth in the extremities, no uniform diagnostic criteria have been established because of the variety in its manifestation. Consequently, no anatomical analysis based on a comparison study has been reported. In this study, the authors determine the frequency of various vascular malformations and abnormal growth and assess any statistical relationship between vascular malformation type/location and abnormal growth in terms of length and girth.
Methods: Thirty-five patients with Klippel-Trenaunay syndrome satisfying the criteria proposed by Oduber et al. in 2008 were enrolled. The type and location of the vascular malformation and abnormal circumferential growth were assessed by magnetic resonance imaging and ultrasonography. Bone girth was assessed by axial magnetic resonance imaging/computed tomography. Plain radiographs of the long bones were used to measure growth in length.
Results: The spectrum of vascular types was similar to that in previous reports. There was no significant association between leg length and vascular malformation type or location. Leg bone circumferential hypoplasia was observed in 50 percent of cases and was significantly related to the presence of intramuscular lesions. A single venous malformation in the subcutaneous tissue was significantly associated with the presence of subcutaneous hypertrophy. Patients with intramuscular lymphatic malformations had a significantly higher frequency of muscle hypoplasia.
Conclusion: The type and location of certain vascular malformations were significantly associated with abnormal subcutaneous tissue, muscle, and bone growth. (Plast. Reconstr. Surg. 127: 340, 2011.)

A New Modified Technique for Removing Epidermal Cysts Using a Trepan in One Stage with a Smaller Postoperative Scar and No Recurrence
Emi Funayama, Akihiko Oyama, Hiroshi Furukawa, Toshihiko Hayashi, Mariko Sugino, Yuhei Yamamoto
DERMATOLOGIC SURGERY, 36, 12, 2050, 2052, WILEY-BLACKWELL PUBLISHING, INC, 2010年12月, ［査読有り］
英語, 研究論文（学術雑誌）, The authors have indicated no significant interest with commercial supporters.

低蛋白血症が原因と推察された熱傷術後の創傷治癒遅延　　　　　　　　　　　　　　　
蕨 雄大, 大野 健太郎, 池田 正起, 大芦 耕平, 七戸 龍司, 林 利彦, 舟山 恵美, 山本 有平
熱傷, 36, 2, 108, 109, (一社)日本熱傷学会, 2010年06月
日本語

Reconstructive considerations in the treetment of soft tissue sarcomas of the cheek.　　　　　　　　　　　　　　　
Saito, N, Tsutsumida, A, Sekido, M, Furukawa, H, Oyama, A, Funayama, E, Saito, A, Yamamoto, Y
ACTA italica, 30, 103-106, 2010年01月
英語, 研究論文（学術雑誌）

Laminin-421 produced by lymphatic endothelial cells induces chemotaxis for human melanoma cells
Noriko Saito, Jun-ichi Hamada, Hiroshi Furukawa, Arata Tsutsumida, Akihiko Oyama, Emi Funayama, Akira Saito, Tsutomu Tsuji, Mitsuhiro Tada, Tetsuya Moriuchi, Yuhei Yamamoto
PIGMENT CELL & MELANOMA RESEARCH, 22, 5, 601, 610, WILEY-BLACKWELL PUBLISHING, INC, 2009年10月, ［査読有り］
英語, 研究論文（学術雑誌）, P>Melanoma has a high tendency to metastasize to lymph nodes, which is one of the clinicopathological factors to indicate poor prognosis. Recent investigations have shown the importance of lymphangiogenesis in lymph node metastasis in a variety of human tumors including melanoma. However, molecular mechanism of lymphatic metastasis is still poorly defined. We examined influence of interactions between normal lymphatic endothelial cells (LECs) and melanoma cells on cell migration. Medium conditioned with LEC (LEC-CM) contained chemotactic and chemokinetic activities for human melanoma cell lines. The chemotactic activity was fractionated in more than 100 kDa, and inactivated by heat-treatment. The chemotactic activity of LEC-CM was abolished by immunodepletion with anti-laminin-1 antibody. And immunoprecipitation and Western blot analyses revealed that LEC-CM contained laminin-421. When melanoma C8161 cells were treated with function-blocking antibodies to integrin alpha 3 or alpha 6, their chemotactic responses to LEC-CM were markedly reduced. Furthermore, the knock-down of tetraspanin CD151 weakened the chemotactic responses of C8161 and MeWo cells to LEC-CM. These data suggest that laminin-421 secreted by LEC possibly facilitates lymphatic metastasis through the induction of chemotaxis of melanoma cells.

Correction of involutional entropion using a rhytidoplasty technique
Masatsugu Kondo, Hidehiko Minakawa, Emi Funayama, Toshihiko Hayashi
European Journal of Plastic Surgery, 32, 4, 181, 184, 2009年08月, ［査読有り］
英語, 研究論文（学術雑誌）, The pathophysiology of involutional entropion is multifactorial and correction of the multiple causes may require use of a combination of procedures. Here, we report the outcome of treatment of entropion of the lower eyelid using the rhytidoplasty and modified Celsus-Hotz procedure for 29 Japanese patients. The patients comprised nine males and 20 females of age 44 to 86 years old (average age 69 years old). A postoperative assessment was performed in our office or by telephone interview. There were no cases of secondary ectropion and almost all of the patients were pleased with the results. This combined procedure is a simple approach with reduced invasiveness that can address almost all the main factors that contribute to formation of involutional entropion in Asian patients. In our patients, postoperative complications were rare and the results were satisfactory in terms of functional and aesthetic improvement. © 2009 Springer-Verlag.

Sebaceous carcinoma of the eyelids: a review of 21 cases.
Saito A, Tsutsumida A, Furukawa H, Saito N, Yamamoto Y
Journal of plastic, reconstructive & aesthetic surgery : JPRAS, 61, 1328, 1331, 11, 2008年11月, ［査読有り］

Simvastatin inhibits growth via apoptosis and the induction of cell cycle arrest in human melanoma cells.
Saito A, Saito N, Mol W, Furukawa H, Tsutsumida A, Oyama A, Sekido M, Sasaki S, Yamamoto Y
Melanoma research, 18, 85, 94, 2, 2008年04月, ［査読有り］

Intraoperative Simulation Device Using Negative Pressure for Construction of Framework in Microtia Reconstruction
Akihiko Oyama, Hideyuki Fujimori, Emi Funayama, Yuhei Yamamoto
PLASTIC AND RECONSTRUCTIVE SURGERY, 121, 3, 129E, 130E, LIPPINCOTT WILLIAMS & WILKINS, 2008年03月, ［査読有り］
英語

[Squamous cell carcinoma of the lower lip, completely responding to concurrent chemoradiotherapy with S-1].
Saito N, Tsutsumida A, Saito A, Furukawa H, Suzuki K, Nishioka T, Yamamoto Y
Gan to kagaku ryoho. Cancer & chemotherapy, 35, 495, 497, 3, 2008年03月, ［査読有り］

Salvage of cartilage framework exposure in microtia reconstruction using a mastoid fascial flap
Akihiko Oyama, Satoru Sasaki, Mol William, Emi Funayama, Yuhei Yamamoto
JOURNAL OF PLASTIC RECONSTRUCTIVE AND AESTHETIC SURGERY, 61, S110, S113, ELSEVIER SCI LTD, 2008年, ［査読有り］
英語, 研究論文（学術雑誌）, One of the common complications of microtia reconstruction with cartilage grafting is exposure of the framework. Recently, we used a mastoid fascial flap for salvage operations in two microtia patients, who had partial skin necrosis with resultant exposure of the cartilage framework. Following the excision of the necrotic skin, the anteriorly based mastoid fascial. flap was elevated and transferred as a hinge flap on to the portion of the exposed framework. Split-thickness skin grafts were applied over the mastoid fascial flap. Each skin graft took well and the relief of the reconstructed ear was preserved in both cases. This salvage method has a large advantage of not leaving any visible scars on the temporal region and the reliability of its rich blood supply. (C) 2006 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Forehead lipoma resection via a small remote incision using a surgical raspatory
Emi Funayama, Hidehiko Minakawa, Akihiko Oyama
JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY, 56, 3, 458, 459, MOSBY-ELSEVIER, 2007年03月, ［査読有り］
英語, 研究論文（学術雑誌）, Lipomas are benign tumors and, therefore, a Surgical technique that does not leave a visible scar would be an ideal method. A forehead lipoma can be extracted using a small remote incision with endoscopic assistance for aesthetic purposes. However, endoscope-assisted surgery is usually technically demanding, time-consuming, and less cost-effective. In this report, we propose an alternative approach to the surgical resection of a forehead lipoma with a small remote incision. Our method uses a surgical raspatory. Our technique allows the complete removal of the lipoma with no complications using a raspatory passed down a subcutaneous tunnel from an incision placed in an aesthetically advantageous site.

Velopharyngeal insufficiency in hemifacial microsomia: Analysis of correlated factors
Emi Funayama, Hiroharu H. Igawa, Noriko Nishizawa, Akihiko Oyama, Yuhei Yamamoto
OTOLARYNGOLOGY-HEAD AND NECK SURGERY, 136, 1, 33, 37, MOSBY-ELSEVIER, 2007年01月, ［査読有り］
英語, 研究論文（学術雑誌）, OBJECTIVE: To investigate the incidence of unilateral hypodynamic palate (UHP) and velopharyngeal insufficiency (VPI) in hemifacial microsomia (HFM), and to determine the dysmorphic manifestations having significant associations with UHP/ VPI in HFM.
STUDY DESIGN: This was a nonrandomized study of 48 patients with unilateral HFM without cleft palate. The correlation between each anomaly and UHP/VPI was analyzed statistically. In addition, we observed 4 HFM patients with cleft palate to examine the influence on cleft palate speech.
RESULTS: The incidence of UHP in HFM was 50.0% and that of VPI was 14.6%. All the VPI patients had UHP. Severe micrognathia and soft tissue deficiency, macrostomia, and mental retardation were significant risk factors for developing VPI in HFM. Moreover, UHP exacerbated speech in HFM with cleft lip and palate.
CONCLUSIONS: Significant correlations were detected between VPI and HFM. This finding should be helpful in the overall management of HFM. (c) 2007 American Academy of Otolaryngology-Head and Neck Surgery Foundation. All rights reserved.

Melanoma of thumb: retrospective study for amputation levels, surgical margin and reconstruction.
Furukawa H, Tsutsumida A, Yamamoto Y, Sasaki S, Sekido M, Fujimori H, Sugihara T
Journal of plastic, reconstructive & aesthetic surgery : JPRAS, 60, 1, 24, 31, 1, 2007年, ［査読有り］

Modification of thoracoscopy in pectus excavatum: insertion of both thoracoscope and introducer through a single incision to maximise visualisation.
Furukawa H, Sasaki S, William M, Sekido M, Tsutsumida A, Oyama A, Yamamoto Y
Scandinavian journal of plastic and reconstructive surgery and hand surgery / Nordisk plastikkirurgisk forening [and] Nordisk klubb for handkirurgi, 41, 4, 189, 192, 4, 2007年, ［査読有り］

CD10が陽性を示したatypical fibroxanthomaの1例
氏家 英之, 加藤 直子, 夏賀 健, 冨田 幸希, 皆川 英彦, 舟山 恵美, 國分 一郎
臨床皮膚科, 60, 13, 1262, 1264, (株)医学書院, 2006年12月
日本語, 79歳男、数か月前より右耳前部に無症候性で小豆大の紅色丘疹を自覚し、表面のびらん化、痂皮の付着を繰り返した。前立腺癌、高血圧症の既往があった。初診時、右耳前部にびらんを伴う暗赤色ドーム状隆起性腫瘍(径10mm)を認めた。毛細血管拡張性肉芽腫などの疑いで全摘出術を施行した。病理組織学的に真皮内に比較的境界明瞭な腫瘍塊を認め、腫瘍細胞は核に多形性を有する紡錘形の線維芽細胞様細胞が主体で、不規則な錯綜配列を呈した。免疫組織化学的にほとんど全ての腫瘍細胞の細胞質でvimentin、CD10陽性であった。atypical fibroxanthomaと診断し、拡大切除を行った。根治術後4か月の現在まで再発や転移は認めなかった。

リンパ節転移をきたした外陰部apocrine ductal carcinomaの1例　　　　　　　　　　　　　　　
夏賀 健, 加藤 直子, 氏家 英之, 冨田 幸希, 皆川 英彦, 舟山 恵美, 木村 中
日本皮膚科学会雑誌, 116, 4, 478, 478, (公社)日本皮膚科学会, 2006年04月
日本語

北海道がんセンターにおけるMerkel cell carcinoma 7例の検討　　　　　　　　　　　　　　　
氏家 英之, 加藤 直子, 夏賀 健, 冨田 幸希, 皆川 英彦, 舟山 恵美
日本皮膚科学会雑誌, 116, 4, 486, 486, (公社)日本皮膚科学会, 2006年04月
日本語

Treatment strategy for cutaneous malignant melanoma.
Tsutsumida A, Furukawa H, Yamamoto Y, Sugihara T
International journal of clinical oncology, 10, 5, 311, 317, 5, 2005年10月, ［査読有り］

二段階口蓋形成術法と一段階口蓋形成術法との比較検討 片側性完全唇顎口蓋裂児の5歳時までの歯槽弓形態変化
熊澤 龍一郎, 伊藤 裕美, 井上 農夫男, 川嶋 邦裕, 三古谷 忠, 松沢 祐介, 飯田 順一郎, 佐々木 了, 斉藤 豪紀, 松岡 真琴, 佐藤 嘉晃, 舟山 恵美, 山本 栄治, 戸塚 靖則, 杉原 平樹, 井川 浩晴
日本口蓋裂学会雑誌, 30, 2, 72, 72, (一社)日本口蓋裂学会, 2005年04月
日本語

Microvascularly augmented Occipito-Cervico-Dorsal flap (OCD flap)により再建した項部慢性膿皮症の1例　　　　　　　　　　　　　　　
皆川 知広, 木村 中, 七戸 龍司, 舟山 恵美, 小山 明彦
日本形成外科学会会誌, 25, 3, 235, 235, (一社)日本形成外科学会, 2005年03月
日本語

Medial pedicled orbicularis oculi flapによる内眼角再建の経験　　　　　　　　　　　　　　　
皆川 知広, 木村 中, 七戸 龍司, 舟山 恵美, 小山 明彦
道南医学会誌, 40, 98, 100, 道南医学会, 2005年03月
日本語, 50歳女.交通事故により顔面に多数の挫創・裂創を受傷し,同日縫合処置を受けた.その後開瞼時に右内眼角から下眼瞼がひきつれる感じが強くなった.受傷6ヵ月後,局所麻酔と静脈麻酔下に瘢痕拘縮の解除ならびに右上眼瞼からのmedial pedicled orbicularis oculi flapによる再建手術を施行した.皮弁のデザインは通常の上眼瞼除皺術に従い眼窩隔膜上で皮弁を挙上し,欠損部に移動した後,欠損形態に合わせて皮弁をトリミングし縫合した.患側からの皮弁だけで欠損部を被覆できたため,健側上眼瞼には除皺術のみを施行した.その後皮弁基部のふくらみに対し,局所麻酔下に修正手術を一度行った.皮弁移行後10ヵ月現在,開瞼時のひきつれ感は著明に改善し,良好な内眼角形態が再現されている

Apoptosis in keloids　　　　　　　　　　　　　　　
Emi Funayama, Thinle Chodon, Akihiko Oyama, Tsuneki Sugihara
Japanese Journal of Plastic and Reconstructive Surgery, 47, 5, 493, 500, 2004年05月
日本語, 研究論文（学術雑誌）, Keloid-derived fibroblasts are refractory to Fas-mediated apoptosis. This indicates that keloids form as a result of an abnormal wound healing process with a prolonged proliferative phase and a delayed remodeling phase that is due to an apoptosis resistant phenotype of the fibroblasts in the keloid lesion. This phenomenon is further enhanced by the overlying keloid keratinocytes.

側頭筋膜弁で再建した耳後部有棘細胞癌の1例　　　　　　　　　　　　　　　
木村 中, 舟山 恵美, 蔵盛 理保子, 古屋 和彦, 七戸 龍司, 皆川 知弘, 小山 明彦
道南医学会誌, 39, 196, 198, 道南医学会, 2004年04月
日本語, 81歳男.2年前より右耳後部に腫瘍が出現し,徐々に拡大した.大きさは21×17mmで,周辺の一部が黒色を呈していた.生検で有棘細胞癌と診断し,中枢側は髪の生え際,遠位側は耳輪の辺縁まで,それぞれ腫瘍から1.5cm,1cm離して耳介軟骨を含め切除した.耳介前面の皮膚のみ残り,再建は拘縮を避け,病理所見を確認するため,人工真皮を貼付し肉芽が形成されてから行う方針とした.病理所見で腫瘍巣は潰瘍表面から2.5mmまでで軟骨への浸潤はなく,surgical marginに腫瘍の残存はなかった.1ヵ月後に再建術を施行し,側頭部に皮切を入れ,筋膜を露出したが,既往脳外科手術の影響で十分な大きさが得られなかった.側頭筋膜を下方に移行し,耳介後面に縫着してその筋膜上に側頭部からの分層皮膚を移植した.術後3ヵ月で腫瘍の再発・転移はなく,耳輪部がやや拘縮して変形しているが,眼鏡・マスクをかけることに支障はない

Change of weight-bearing pattern before and after plantar reconstruction with free anterolateral thigh flap.
Sekido M, Yamamoto Y, Furukawa H, Sugihara T
Microsurgery, 24, 4, 289, 292, 4, 2004年, ［査読有り］

Keratinocytes promote proliferation and inhibit apoptosis of the underlying fibroblasts: An important role in the pathogenesis of keloid
E Funayama, T Chodon, A Oyama, T Sugihara
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 121, 6, 1326, 1331, BLACKWELL PUBLISHING INC, 2003年12月, ［査読有り］
英語, 研究論文（学術雑誌）, Interactions between epidermal keratinocytes and dermal fibroblasts play an important role in regulating tissue homeostasis and repair. Nevertheless, little is known about the role of keratinocytes in the pathogenesis of keloid. In this study, we investigated the influence of normal skin- and keloid-derived keratinocytes on normal skin- and keloid-derived fibroblasts utilizing a serum-free indirect coculture system. The keloid-derived fibroblasts showed a greater proliferation and minimal apoptosis when cocultured with normal skin- or keloid-derived keratinocytes, and the results were most significant in the latter. This difference was not observed when the fibroblasts were treated with conditioned medium obtained from normal skin- and keloid-derived keratinocytes. Nevertheless, conditioned medium-treated groups showed more proliferation and less apoptosis compared to the nonconditioned medium-treated control groups. We also analyzed the profile of factors involved in cell growth and apoptosis in fibroblasts cocultured with keratinocytes. Extracellular signal-regulated kinase and c-Jun N-terminal kinase phosphorylations and expression of Bcl-2 and transforming growth factor-beta1 were all significantly upregulated in the fibroblasts cocultured with keloid-derived keratinocytes. Together, these results strongly suggest that the overlying keratinocytes of the keloid lesion play an important role in keloidogenesis by promoting more proliferation and less apoptosis in the underlying fibroblasts through paracrine and double paracrine effects.

頭部血管肉腫の1手術例
木村 中, 舟山 恵美, 古屋 和彦, 横山 朋子, 林 利彦
Skin cancer : official organ of the Japanese Society for Skin Cancer = 皮膚悪性腫瘍研究会機関誌, 18, 1, 51, 55, The Japanese Skin Cancer Society, 2003年05月30日
日本語, Angiosarcoma of the scalp is a relatively rare malignant endothelial tumor. We experienced a case of angiosarcoma treated by wide local excision. An 85-year-old man was admitted to our hospital with a tumor which had appeared 1 month before on his left temporal region. The diagnosis of angiosarcoma was made based on the clinical features and histopathological finding of the lesions on the skin by a former institution. We performed wide local excision immediately circumferentially to a distance of more than 3-5cm from the tumor margin. At present, 13 months after surgery, no recurrence or metastasis has been observed. [Skin Cancer (Japan) 2003; 18: 51-55]

顎裂を伴わない唇裂患者の梨状孔の骨形態
木村 中, 舟山 恵美, 早坂 登喜子, 村井 茂, 横山 朋子
日本口蓋裂学会雑誌, 28, 1, 20, 27, 一般社団法人 日本口蓋裂学会, 2003年04月30日
日本語, 顎裂や口蓋裂を伴わない唇裂患者の上顎の骨形態にも変形が存在することは報告があるが,われわれは過去には特別に注意を払うことがなかった。しかし顎裂・口蓋裂を伴わない唇裂として長期間経過観察されていた症例の中で,梨状孔に骨欠損,あるいは骨の変形や左右非対称を認めた症例を経験したので報告した。症例は6例で,男性2例女性4例であった。右唇裂と診断されていたものが5例で左唇裂と診断されでいたものが1例であった。いずれの症例も唇裂と診断されており,顎裂は認めなかったが,三次元CTを撮影したところ梨状孔の骨形態に変形を認めた。6例中2例で自家骨を移植し,他の2例で人工骨を移植した。2例は骨に対する処置は行わなかった。顎裂を伴わない片側唇裂の症例で,患側鼻翼基部の陥凹を修正する際に軟部組織だけを形成しても良好な外鼻形態が形成できないことをしばしば経験するが,梨状孔の形態にも着目し,外鼻の支持組織である硬組織に変形が認められるときには,自家骨や人工骨の移植によって硬組織をしっかり形成することが重要と考えた。その際,唇裂のみの症例でも鼻筋の修正や鼻孔底の形成も重要であるが,それは個々の症例の変形の程度に応じて行わなければならない。

[A study of interaction between keratinocytes and fibroblasts in keloid].
Funayama E
[Hokkaido igaku zasshi] The Hokkaido journal of medical science, 77, 6, 533, 541, 北海道大学, 2002年11月, ［査読有り］
日本語

Two innovations of the star-flap technique for nipple reconstruction
YAMAMOTO Y, FURUKAWA H, OYAMA A, HORIUCHI K, FUNAYAMA E, TSUTSUMIDA A, SUGIHARA T, NOHIRA K
British Journal of Plastic Surgery, 54, 8, 723, 726, 2001年

Keloid-derived fibroblasts are refractory to Fas-mediated apoptosis and neutralization of autocrine transforming growth factor-beta 1 can abrogate this resistance
T Chodon, T Sugihara, HH Igawa, E Funayama, H Furukawa
AMERICAN JOURNAL OF PATHOLOGY, 157, 5, 1661, 1669, AMER SOC INVESTIGATIVE PATHOLOGY, INC, 2000年11月, ［査読有り］
英語, 研究論文（学術雑誌）, The pathogenesis of keloid remains poorly understood. As no effective therapy for keloid is as yet available, an Insight Into its pathogenesis may lead to novel approaches. Apoptosis has been found to mediate the decrease in cellularity during the transition between granulation tissue and scar. Here, we report that In contrast to hypertrophic scar-derived and normal skin-derived fibroblasts, keloid-derived fibroblasts are significantly resistant to both Fas-mediated and staurosporine-induced apoptosis, The caspases-3, -8, and -9 were not activated indicating that the block In the apoptotic pathway in keloid is upstream of the caspases. There were no significant differences in the level of expression of Fas, Bcl-2, acid Bax between the three groups but addition of transforming growth factor (TGF)-beta1 significantly inhibited Fas-mediated apoptosis in hypertrophic scar-derived and normal shin-derived fibroblasts and neutralization of autocrine TGF-beta1 with anti-TGF-beta1 antibody abrogated the resistance of keloid-derived fibroblasts, Anti-apoptotic activity was not observed with TGF-beta2, This is the first study linking refractory Fas-mediated apoptosis to cellular phenotype in keloids and indicating a pivotal role for the anti-apoptotic effect of TGF-beta1 in this resistance. Hence, it becomes important to treat keloids as a separate entity different from hypertrophic scars and enhancement of Fas-sensitivity could be a promising therapeutic target.

放射線照射後に生じた多発性基底細胞上皮腫の1例
木村 中, 南本 俊之, 浜田 美実, 佐々木 晴恵, 古屋 和彦, 舟山 恵美
Skin cancer : official organ of the Japanese Society for Skin Cancer = 皮膚悪性腫瘍研究会機関誌, 13, 2, 158, 162, The Japanese Skin Cancer Society, 1998年10月30日
日本語, Malignant skin tumors are known to develop in areas of chronic radiodermatitis. We experienced a patient with multiple basal cell carcinomas that developed about 50 years after irradiation. The patient was a 77-year-old man who underwent radiotherapy in his twenties for caries in the left shoulder joint. The dose given was unknown. Black skin tumor appeared initially about 10 years before the first consultation. The skin around the tumor began to erode about six months before presentation. Biopsy of the tumor was done at another institution and revealed basal cell carcinoma(BCC), so the patient was referred to our department. In addition to the BCC measuring 35×20mm in the left shoulder, BCC measuring 17×20mm and 15×15mm were found on the chest and the left axilla, respectively. The lesions were excised with a margin of 5mm from the radiodermatitis, and the resultant skin defects were covered with latissimus dorsi flaps. All three tumors were basal cell carcinomas. The patient died of an unrelated disease six years after surgery and there was no recurrence of his tumors.

New Design Concept of Nasolabial Flap for the Reconstruction of a Complex Defect in the Alar Base
Toshihiko Hayashi, Taku Maeda, Yuhei Yamamoto, Emi Funayama, Facial Plastic Surgery, 37, 1, 134, 135, 2021年02月01日
Thieme Medical Publishers, Inc., 英語, 速報，短報，研究ノート等（学術雑誌）

上肢の電撃傷に対して遊離大網移植術を施行した1例
高橋 紀久子, 坂本 泰輔, 舟山 恵美, 蕨 雄大, 岩嵜 大輔, 佐藤 千草, 木村 中, 創傷, 9, 4, 126, 130, 2018年10月
35歳男性。高電圧(22000V)の機器を整備中に左環指の指輪にアーク放電し、右前腕にIII度熱傷の電撃傷を受傷した。手背は左大腿部からの分層植皮、前腕は人工真皮の移植を行った。手背部は生着したが、前腕部は筋壊死が進行し、CTAで前腕部に尺骨動脈の血流途絶を認めた。デブリードマンと遊離大網移植による再建術を行ったが、術後2ヵ月より移植部に排膿を伴う多数の小瘻孔が出現する様になった。大網弁の深部に残存している腱組織が壊死に至った部分が感染巣と判断し、その都度、大網弁を切開し、壊死組織を除去した。術後3ヵ月より機能再建を目的に腱移行・腱移植術などを行った。受傷後9ヵ月に尺骨の骨髄炎を認め、腐骨を除去した。本例は感染巣の除去や機能再建術のため、大網弁の移植を計10回以上、様々な箇所を切開したが、切開部では良好な創治癒が得られた。受傷から創部が完全治癒するまで4年8ヵ月を要した。, (一社)日本創傷外科学会, 日本語

【顔面神経麻痺の治療アルゴリズム:ベストプラクティス】 当教室の顔面神経麻痺に対する外科治療のアルゴリズム　　　　　　　　　　　　　　　
古川 洋志, 大澤 昌之, 小山 明彦, 村尾 尚規, 林 利彦, 舟山 恵美, 山本 有平, 日本頭蓋顎顔面外科学会誌, 34, 1, 16, 20, 2018年04月
(一社)日本頭蓋顎顔面外科学会, 日本語

当科における馬顔面外傷の治療経験
藤田宗純, 小山明彦, 大澤昌之, 村尾尚規, 林利彦, 舟山恵美, 山本有平, 日本頭蓋顎顔面外科学会誌, 33, 3, 87‐92, 2017年09月25日
日本語

片側唇顎口蓋裂に対する一期手術全51症例の経過(その1)　　　　　　　　　　　　　　　
小山 明彦, 岡本 亨, 舟山 恵美, 佐藤 嘉晃, 西澤 典子, 今井 智子, 山本 有平, 日本口蓋裂学会雑誌, 42, 2, 93, 93, 2017年04月
(一社)日本口蓋裂学会, 日本語

片側唇顎口蓋裂に対する一期手術全51症例の経過(その2)　　　　　　　　　　　　　　　
小山 明彦, 岡本 亨, 舟山 恵美, 佐藤 嘉晃, 西澤 典子, 今井 智子, 山本 有平, 日本口蓋裂学会雑誌, 42, 2, 94, 94, 2017年04月
(一社)日本口蓋裂学会, 日本語

ケロイド・肥厚性瘢痕切除後の電子線照射とステロイド局注療法に関する考察 患者アンケート調査を通じて　　　　　　　　　　　　　　　
池田 正起, 林 利彦, 村尾 尚規, 舟山 恵美, 小山 明彦, 山本 有平, 瘢痕・ケロイド治療ジャーナル, 10, 1, 6, 2016年08月
ケロイド・肥厚性瘢痕切除後の電子線照射とステロイド局注療法について検討した。ケロイド、肥厚性瘢痕に対して手術療法を行った後にステロイド強化療法を行った40例(男性8名、女性32名、平均44.5歳)および電子線照射を行った5例(男性3名、女性2名、平均39.4歳)を対象にアンケートを実施し、24例から回答を得た。「電子線照射とステロイド強化療法の説明をきいて、ステロイド強化療法を選択された理由についてお答え下さい。」に関して45件の回答があった。最も多かった回答は「手術からその後の治療まで同じ主治医(形成外科)が行う方が安心」という項目で67%、次に「通院の頻度が自分に合っている」という項目で46%であった。「実際にステロイド強化療法を行ってみて、その結果についてどのようにお考えでしょうか」に関して24件の回答があり、「満足」が54%、「やや満足」と合わせると75%となった。電子線照射を選択した症例の治療選択理由は、植皮、皮弁を行った広範囲が3例、遠方で定期的な通院が不可能なため入院治療を行った例が1例、ステロイド注射の疼痛を理由に電子線照射を選択したが1例であった。, (株)全日本病院出版会, 日本語

自家培養表皮が効果的となりうる症例の選択 北海道大学病院における5年間の広範囲熱傷症例の検討　　　　　　　　　　　　　　　
藤田 宗純, 村尾 尚規, 山尾 健, 七戸 龍司, 林 利彦, 舟山 恵美, 小山 明彦, 古川 洋志, 山本 有平, 熱傷, 42, 2, 64, 70, 2016年06月
2009年1月より保険収載された自家培養表皮(ジェイス)は、自家植皮のための恵皮面積が確保できない重篤な広範囲熱傷において有効な治療の選択肢となっている。広範囲熱傷患者において自家培養表皮を使用するには、皮膚組織を採取してから培養、シート作成までに約3週間を要する点、感染対策や移植床の再構築を必須とする点など、乗り越えるべき問題も多い。計画どおりに移植まで到達する過程が重要であり、自家培養表皮の使用効果が十分に発揮できる症例を見極める必要がある。そこで、自家培養表皮の使用が効果的となりうる急性期熱傷症例の選択について、当院の過去5年間の治療結果をもとに検討した。2010年1月から2014年12月までの5年間に当院へ救急搬送後、形成外科で手術治療を行った急性期熱傷症例のうち、自家培養表皮使用の保険適応を満たす症例を対象とした。患者の年齢、性別、受傷部位、受傷面積、熱傷指数(以下BI)、熱傷予後指数(PBI)、転帰について検討した。さらに自家培養表皮移植を行った症例では、移植部位、移植床、移植方法、表皮形成率、BI層別(BI40〜50未満、BI60〜80未満)の生存率および表皮形成率について検討を加えた。自家培養表皮の保険適応症例は全9例(男性6例、女性3例)あり、年齢は19歳から72歳で、平均年齢は39.9歳であった。自家培養表皮を使用した症例は6例あった。自家培養表皮移植症例6例中4例がBI40から50未満で、生存率は100%、平均表皮形成率は62.5%であった。一方、6例中2例でBI60から80未満に使用し、2例とも死亡し、最終的な平均表皮形成率は0%であった。われわれの経験では、自家培養表皮の使用効果が得られやすい症例はBI40から50前後と考えられた。広範囲熱傷に対して自家培養表皮を適切に使用することで救命率の向上につながると思われる。(著者抄録), (一社)日本熱傷学会, 日本語

当科における色素性母斑のレーザー治療　　　　　　　　　　　　　　　
伊藤 梨里, 小山 明彦, 佐々木 了, 舟山 恵美, 古川 洋志, 林 利彦, 山本 有平, 日本レーザー医学会誌, 36, 4, 529, 529, 2016年01月
(NPO)日本レーザー医学会, 日本語

片側唇裂口蓋裂における口蓋形成術術式の違いによる言語成績の評価　　　　　　　　　　　　　　　
舟山 恵美, 小山 明彦, 西澤 典子, 三古谷 忠, 今井 智子, 岡本 亨, 佐藤 嘉晃, 山本 有平, 日本頭蓋顎顔面外科学会誌, 31, 3, 218, 218, 2015年10月
(一社)日本頭蓋顎顔面外科学会, 日本語

成人まで観察し得たCarpenter症候群の1症例　　　　　　　　　　　　　　　
伊藤 梨里, 小山 明彦, 舟山 恵美, 山本 有平, 日本頭蓋顎顔面外科学会誌, 31, 3, 247, 247, 2015年10月
(一社)日本頭蓋顎顔面外科学会, 日本語

Marchac Frontal Modelを用いたCraniosynostosis頭蓋形成~その有用性とわれわれの工夫~
小山明彦, 古川洋志, 舟山恵美, 林利彦, 山本有平, 黒田敏, 中山若樹, 日本形成外科学会会誌, 34, 10, 780, 2014年10月20日
日本語

解剖学的サブユニットに最大限配慮した片側唇裂初回口唇形成術 (特集 口唇裂初回手術 : 最近の術式とその中期的結果) -- (片側口唇裂初回口唇形成術)
小山 明彦, 舟山 恵美, 山本 有平, Pepars, 89, 16, 22, 2014年05月
全日本病院出版会, 日本語

常染色体22q11.2欠失症候群の経過分析　　　　　　　　　　　　　　　
村尾 尚規, 小山 明彦, 舟山 恵美, 山本 有平, 西澤 典子, 福田 諭, 日本形成外科学会会誌, 34, 4, 312, 312, 2014年04月
(一社)日本形成外科学会, 日本語

特異な臨床像を呈したMadelung病(両側対称性脂肪腫症)の1例　　　　　　　　　　　　　　　
伊藤 梨里, 舟山 恵美, 林 利彦, 古川 洋志, 小山 明彦, 山本 有平, 日本形成外科学会会誌, 34, 4, 311, 311, 2014年04月
(一社)日本形成外科学会, 日本語

片側唇顎口蓋裂に対する一期手術 全16例の短期経過　　　　　　　　　　　　　　　
小山 明彦, 舟山 恵美, 古川 洋志, 林 利彦, 山本 有平, 岡本 亨, 西澤 典子, 今井 智子, 佐藤 嘉晃, 日本形成外科学会会誌, 33, 11, 865, 865, 2013年11月
(一社)日本形成外科学会, 日本語

術式の違いによる片側唇顎口蓋裂4歳時言語成績の検討　　　　　　　　　　　　　　　
舟山 恵美, 小山 明彦, 山本 有平, 西澤 典子, 今井 智子, 三古谷 忠, 三上 愛, 佐々木 了, 岡本 亨, 日本形成外科学会会誌, 33, 11, 866, 866, 2013年11月
(一社)日本形成外科学会, 日本語

Real-time Virtual Sonography を用いた前外側大腿皮弁の術前評価
齋藤 亮, 古川 洋志, 林 利彦, 小山 明彦, 舟山 恵美, 山本 有平, 北海道醫學雜誌 = Acta medica Hokkaidonensia, 87, 6, 264, 264, 2012年11月01日
日本語

Hemifacial Microsomia における鼻咽腔閉鎖機能不全 : 関連因子の解析について
舟山 恵美, 日形会誌 : 日本形成外科学会会誌 = Journal of Japan Society of Plastic and Reconstructive Surgery, 32, 10, 775, 776, 2012年10月20日
日本語

片側唇顎口蓋裂に対する一期手術 全15例の短期経過　　　　　　　　　　　　　　　
小山 明彦, 岡本 亨, 舟山 恵美, 佐藤 嘉晃, 西澤 典子, 今井 智子, 山本 有平, 日本口蓋裂学会雑誌, 37, 2, 111, 111, 2012年04月
(一社)日本口蓋裂学会, 日本語

口蓋形成術術式の違いによる言語成績の検討 片側唇顎口蓋裂4歳時の評価　　　　　　　　　　　　　　　
舟山 恵美, 小山 明彦, 西澤 典子, 三古谷 忠, 今井 智子, 三上 愛, 佐々木 了, 日本口蓋裂学会雑誌, 37, 2, 133, 133, 2012年04月
(一社)日本口蓋裂学会, 日本語

口唇口蓋裂治療 未来へのネットワーク 理想的なチーム医療を目指して 北海道大学病院における口唇・口蓋裂チーム医療 歴史と現況　　　　　　　　　　　　　　　
小山 明彦, 舟山 恵美, 佐藤 嘉晃, 上田 康夫, 三古谷 忠, 西澤 典子, 今井 智子, 岡本 亨, 山本 有平, 日本口蓋裂学会雑誌, 37, 2, 75, 75, 2012年04月
(一社)日本口蓋裂学会, 日本語

壊死性筋膜炎の評価 : LRINEC score および予測死亡率評価ツールを用いて
前田 拓, 舟山 恵美, 山本 有平, 日形会誌 : 日本形成外科学会会誌 = Journal of Japan Society of Plastic and Reconstructive Surgery, 32, 2, 63, 68, 2012年02月20日
日本語

Hemifacial Microsomia における鼻咽腔閉鎖機能不全-関連因子の解析
舟山 恵美, 井川 浩晴, 西澤 典子, 小山 明彦, 山本 有平, 日形会誌 : 日本形成外科学会会誌 = Journal of Japan Society of Plastic and Reconstructive Surgery, 31, 11, 735, 740, 2011年11月20日
日本語

口蓋裂治療アップデート　　　　　　　　　　　　　　　
小山 明彦, 舟山 恵美, 西澤 典子, 今井 智子, 佐藤 嘉晃, 岡本 亨, 山本 有平, 耳鼻咽喉科展望, 54, 5, 279, 286, 2011年10月
耳鼻咽喉科展望会, 日本語

口蓋裂二次手術としてのFurlow法 鼻腔ファイバースコープ所見に基づく適応判断　　　　　　　　　　　　　　　
小山 明彦, 舟山 恵美, 古川 洋志, 林 利彦, 山本 有平, 西澤 典子, 日本形成外科学会会誌, 31, 5, 344, 344, 2011年05月
(一社)日本形成外科学会, 日本語

口蓋裂二次手術としてのFurlow法 鼻腔ファイバースコープ所見に基づく適応判断について　　　　　　　　　　　　　　　
小山 明彦, 西澤 典子, 佐々木 了, 舟山 恵美, 林 利彦, 大澤 昌之, 山本 有平, 日本頭蓋顎顔面外科学会誌, 26, 2, 143, 143, 2010年06月
(一社)日本頭蓋顎顔面外科学会, 日本語

上眼瞼除皺術による老人性眼瞼下垂症の治療経験--年齢による皮膚切除幅の検討
近藤 雅嗣, 皆川 英彦, 舟山 恵美, 形成外科, 53, 1, 73, 78, 2010年01月
克誠堂出版, 日本語

頭蓋顔面骨切り術の術前計画と手術の実際 上下顎 上下顎骨切り術の術前計画と手術の実際 Desirable ProfileとDesirable Occlusionの両立のために　　　　　　　　　　　　　　　
小山 明彦, 佐々木 了, 大澤 昌之, 上田 康夫, 佐藤 嘉晃, 舟山 恵美, 山本 有平, 日本頭蓋顎顔面外科学会誌, 25, 2, 88, 88, 2009年06月
(一社)日本頭蓋顎顔面外科学会, 日本語

皮膚の創傷治癒の基礎 (創傷治療)
舟山 恵美, 山本 有平, 治療, 91, 2, 227, 231, 2009年02月
南山堂, 日本語

北海道がんセンターにおける過去13年間の悪性黒色腫87例の検討　　　　　　　　　　　　　　　
山根 尚子, 加藤 直子, 大澤 倫子, 柳 輝希, 皆川 英彦, 舟山 恵美, 夏賀 健, 日本皮膚科学会雑誌, 119, 1, 66, 66, 2009年01月
(公社)日本皮膚科学会, 日本語

北海道がんセンターにおける過去14年間の悪性黒色腫90例の検討　　　　　　　　　　　　　　　
山根 尚子, 加藤 直子, 大澤 倫子, 柳 輝希, 伊藤 幹, 西村 真智子, 皆川 英彦, 舟山 恵美, 林 利彦, 夏賀 健, 日本皮膚科学会雑誌, 118, 10, 2024, 2024, 2008年09月
(公社)日本皮膚科学会, 日本語

私たちの考える痕跡唇裂の形態解剖とそれに基づく手術方法
小山 明彦, 山本 有平, 佐々木 了, 林 利彦, 舟山 恵美, 日本口蓋裂学会雑誌, 31, 2, 129, 129, 2006年04月30日
日本語

先天性両側鼻孔狭窄の1例
近藤 雅嗣, 皆川 英彦, 舟山 恵美, 山本 有平, 日形会誌 : 日本形成外科学会会誌 = Journal of Japan Society of Plastic and Reconstructive Surgery, 25, 10, 686, 689, 2005年10月20日
日本語

口蓋裂術後鼻咽腔閉鎖機能不全の発生要因の検討
小山 明彦, 井川 浩晴, 川嶋 邦裕, 佐々木 了, 西澤 典子, 舟山 恵美, 山本 有平, 杉原 平樹, 日本口蓋裂学会雑誌, 30, 2, 189, 189, 2005年04月30日
日本語

われわれの工夫(16)唇裂外鼻変形に対する手術におけるわれわれの工夫
木村 中, 舟山 恵美, 蔵盛 理保子, 形成外科, 47, 3, 241, 243, 2004年03月
克誠堂出版, 日本語

当科で経験した鼻部の基底細胞癌の検討
木村 中, 舟山 恵美, 本間 豊大, 小山 明彦, 北村 孝, 小林 朋子, 村尾 尚規, 日本頭蓋顎顔面外科学会誌 = Journal of the Japan Society of Cranio-Maxillo-Facial Surgery, 19, 2, 117, 124, 2003年09月25日
日本語

熱傷による耳介変形の再建の経験
木村 中, 南本 俊之, 畠 真也, 齋藤 亮, 皆川 英彦, 舟山 恵美, 小山 明彦, 熱傷, 26, 3, 131, 139, 2000年09月15日
日本語

先天性鼻咽腔閉鎖機能不全を呈したHemifacial Microsomiaの1例　　　　　　　　　　　　　　　
舟山 恵美, 井川 浩晴, 坂村 律生, 杉原 平樹, 畠 真也, 西澤 典子, 日本頭蓋顎顔面外科学会誌, 15, 1, 172, 172, 1999年04月
(一社)日本頭蓋顎顔面外科学会, 日本語

手指切断を要した熱傷例の検討
木村 中, 南本 俊之, 國分 一郎, 舟山 恵美, 熱傷, 25, 1, 28, 36, 1999年03月15日
日本語

手指切断を要した熱傷例の検討
木村 中, 南本 俊之, 國分 一郎, 舟山 恵美, 熱傷, 24, 4, 219, 219, 1998年11月15日
日本語

入浴中のてんかん発作による熱傷の2例
木村 中, 北村 孝, 金澤 浩之, 舟山 恵美, 熱傷, 24, 1, 30, 35, 1998年03月15日
日本語

入浴中のてんかん発作により手術を要する熱傷を受傷した2例
木村 中, 北村 孝, 金澤 浩之, 舟山 恵美, 熱傷, 23, 4, 327, 327, 1997年11月15日
日本語

爪下外骨腫の治療 : 爪床欠損を伴うものに人工真皮を用いた経験
木村 中, 金澤 浩之, 小山 明彦, 舟山 恵美, 日本形成外科学会会誌, 16, 5, 332, 342, 1996年05月31日
日本語

美容外科に必須の形成外科の基本知識と手技 （形成外科 増刊号 第58巻 2015年）
杠俊介, 野平久仁彦, 山脇孝徳, 三川信之, 渡辺頼勝, 山下昌信, 倉片優, 柏克彦, 上田和毅, 舟山恵美, 平林慎一, 川上重彦, 清川兼輔
克誠堂出版, 2015年, ［共著］

続発性リンパ浮腫における急性期重症化を防ぐ！レグネース１を標的とした新たな治療法
科学研究費助成事業
2024年04月01日 - 2027年03月31日
佐藤 千草, 舟山 恵美, 松田 識郁, 石川 耕資, 前田 拓
日本学術振興会, 基盤研究(C), 北海道大学, 24K12817

リキッドバイオプシーによる脈管奇形の遺伝子診断と個別化医療への応用
科学研究費助成事業
2023年04月01日 - 2026年03月31日
石川 耕資, 山本 有平, 舟山 恵美, 前田 拓
日本学術振興会, 基盤研究(C), 北海道大学, 23K09072

低酸素応答システム活性化薬剤を用いた下肢慢性創傷の新治療
科学研究費助成事業
2020年04月01日 - 2023年03月31日
大澤 昌之, 舟山 恵美, 山本 有平, 前田 拓, 石川 耕資, 林 利彦
創傷治癒過程において酸素環境は重要である。生体は低酸素状態に対する適応応答としてHIF-1α (hypoxia inducible factor-1 alpha) を発現することで、血管新生などの創傷治癒の多段階で作用し、創傷治癒を促進するとされる。
本研究は、リンパ浮腫・虚血・糖尿病を念頭に置いたマウス下肢慢性創傷モデルを用いてHIF-1α調整薬剤の創傷治癒に与える影響を検証し、生体が本来もつ低酸素応答システムを利用した、新たな慢性創傷に対する治療法の開発を目的とした。
本年度は、２年目の計画に従い、初年度で行ったマウス後肢リンパ浮腫モデルを利用した創傷モデルの作成、Roxadustat（HIF-1α安定化薬）およびYC-１（HIF-1α阻害薬）の容量用法の検討に基づき、薬剤投与群と非投与群の間で創傷治癒期間および各タイムポイントでの創傷閉鎖割合に差があるかどうかを検討した。
作成した群は、①皮膚切開のみのコントロール（手術なし・薬剤非投与群）②リンパ浮腫モデル（薬剤非投与群）③リンパ浮腫モデル（Roxadustat投与群）④リンパ浮腫モデル（YC-1投与群）の4群であり、それぞれ大腿部に創傷を作成した。
皮膚切開のみのコントロール（手術なし・薬剤非投与群）に比してリンパ浮腫モデル（薬剤非投与群）は有意に創傷治癒期間が遅延した。また、通常のリンパ浮腫モデル（薬剤非投与群）に比して、Roxadustat（HIF-1α安定化薬）を使用した群で、創傷治癒期間の短縮および創閉鎖割合が促進し、YC-１（HIF-1α阻害薬）を使用した群で、創傷治癒期間の延長および創閉鎖割合が減少する傾向が見られた。また、薬剤を投与したリンパ浮腫モデル群間で後肢の周径の差および皮膚厚の差を認めた。これにより、リンパ浮腫の動態に対しても薬剤による影響がある可能性が示唆された。
日本学術振興会, 基盤研究(C), 北海道大学, 20K09841

低酸素応答システムからケロイド病態を斬る！～局所免疫の正常化と炎症・線維化の抑制
科学研究費助成事業
2020年04月01日 - 2023年03月31日
村尾 尚規, 山本 有平, 林 利彦, 舟山 恵美, 前田 拓, 石川 耕資
ケロイドは創傷治癒過程の異常により炎症と線維化が亢進した状態である。抗原とサイトカインの刺激を受けたCD4陽性T細胞、制御性T細胞とTh17細胞は相互に制御しバランスを保っており、炎症性疾患の発症や病態は制御性T細胞とTh17細胞のバランスにより影響される。われわれは既報でケロイド内では制御性T細胞の発現が低下し、免疫バランスの破綻により 炎症が遷延し線維化が亢進することを報告した。一方、近年ケロイド内は、低酸素状態であることがわかってきた。低酸素誘導因子(hypoxia-inducible factor、HIF)は、酸素供給が滞った組織内の細胞で活性化し 様々な遺伝子の発現を誘導し、生体の環境への適応を促す転写因子である。HIFは低酸素適応応答だけでなく、炎症や悪性腫瘍の病態にも関与する。HIFのサブタイプの中でも、ケロイド内ではHIF-1αの発現が亢進しており、低酸素状態を反映していると考えられる。HIF-1αはTh17細胞への分化を促進するが、制御性T細胞への分化を抑制し、免疫バランスを破綻させる。ケロイドにおいても持続的なHIF-1αの発現亢進が制御性T細胞とTh17細胞の免疫バランスを破綻させることで、ケロイド病態を悪化させている可能性があると仮定し、本研究を計画した。本年度は、文書による同意を得て、17例のケロイド患者からケロイド組織の採取を行い、そのうち15例から血液サンプルを採取することができた。採取した組織の部位別内訳は、耳垂7例、耳介6例、頚部1例、肩部1例、臍部2例であった。パラフィンブロック作成及び初代培養を行い、線維芽細胞を凍結保存した。また、採取した血液検体からLeucosep管を用いて末梢血単核球を分離し、凍結保存した。今後はこれらの検体を使用して共培養を行う予定である。
日本学術振興会, 基盤研究(C), 北海道大学, 20K09858

内臓脂肪の潜在能力：循環と免疫賦活におけるhyper 2-way player
科学研究費助成事業
2019年04月01日 - 2022年03月31日
山本 有平, 林 利彦, 舟山 恵美, 石川 耕資, 前田 拓, 小山 明彦, 古川 洋志
近年，局所のリンパ機能破綻に対するリンパ系再構築法としてさまざまな材料を用いた再建が報告されている。本研究では内臓脂肪の中でも免疫的に中心の役割を担うとされる大網に着目し，マウスを用いた動物実験モデルで検証を行った。
有茎組織弁として血流を保持した状態での移植を行う有茎大網移植モデルと，より侵襲の少ない遊離大網移植モデルを考案し，各群のリンパ系再構築に関する寄与を比較・検証した。結果いずれの群でもリンパ系の再構築を促進する可能性が示唆された。
日本学術振興会, 基盤研究(B), 北海道大学, 19H03811

羊膜由来幹細胞の大いなる可能性～理想的な乳房再建を目指して　　　　　　　　　　　　　　　
科学研究費補助金(基盤研究(C))
2018年04月 - 2021年03月
舟山恵美
日本学術振興会, 研究代表者, 競争的資金

下肢慢性創傷の治癒促進に向けた低酸素応答システム制御の試み
科学研究費助成事業
2017年04月01日 - 2020年03月31日
七戸 龍司, 舟山 恵美, 山本 有平, 村尾 尚規
日本学術振興会, 基盤研究(C), 北海道大学, 17K11526

機能的リンパ組織移植法の開発!　　　　　　　　　　　　　　　
科学研究費補助金(基盤研究(B))
2016年04月 - 2019年03月
山本 有平
日本学術振興会, 競争的資金

郭清術後のリンパ組織再構築術～悪性黒色腫予後の改善を目指して！　　　　　　　　　　　　　　　
科学研究費補助金(基盤研究(B))
2015年04月 - 2018年03月
古川 洋志
日本学術振興会, 競争的資金

ケロイドの免疫細胞治療を目指して！～制御性T細胞は炎症＆線維化を抑制する～　　　　　　　　　　　　　　　
科学研究費補助金(基盤研究(B))
2014年04月 - 2017年03月
村尾 尚規
日本学術振興会, 競争的資金

リンパ浮腫を薬で治す！～DDS技術を駆使したVEGF-C徐放治療の開発　　　　　　　　　　　　　　　
科学研究費補助金(基盤研究(C))
2014年04月 - 2017年03月
小山 明彦
日本学術振興会, 競争的資金

筋肉内静脈網を利用したNeurotization～培養シュワン細胞の血管内遊走　　　　　　　　　　　　　　　
科学研究費補助金(挑戦的萌芽研究)
2014年04月 - 2016年03月
古川 洋志
日本学術振興会, 競争的資金

免疫抑制剤による新しいケロイド治療を目指して ～共培養モデルを用いた検討～　　　　　　　　　　　　　　　
科学研究費補助金(挑戦的萌芽研究)
2013年04月 - 2016年03月
山本有平
日本学術振興会, 競争的資金

悪性黒色腫における腫瘍免疫の破綻を解明する！～マウスリンパ浮腫モデルを用いて～　　　　　　　　　　　　　　　
科学研究費補助金(基盤研究(B))
2013年04月 - 2016年03月
山本 有平
学術振興会, 競争的資金

皮弁移植後リンパ流を可視化する！～光イメージングを用いた再生メカニズムの解明
科学研究費助成事業
2012年04月01日 - 2015年03月31日
堀内 勝己, 山本 有平, 古川 洋志, 小山 明彦, 舟山 恵美, 林 利彦, 大澤 昌之, 関堂 充, 林 利彦
マウス後肢リンパ浮腫モデルにおいて足底に注入したインドシアニングリーン（ICG）の蛍光強度の変化をin vivo imaging systemを用いて経時的に測定した。蛍光強度の低下とリンパ流の改善は相関するものと考えた。また足の体積を測定することにより浮腫（むくみ）の程度を定量化し、経時的な観察を行った。浮腫の改善の傾きと、蛍光強度の低下（＝リンパ流の回復）の間に一定の相関関係を認めた。
リンパ浮腫の動物モデルを用いた研究において、浮腫の程度を定量化する手法はまだ確立されていない。本研究の結果は今後ひとつの定量化の手法としてリンパ浮腫研究の発展に貢献する可能性があると考えられる。
日本学術振興会, 基盤研究(C), 北海道大学, 24592704

側側縫合によるNetwork型再建～神経信号付加の更なる効率化～　　　　　　　　　　　　　　　
科学研究費補助金(挑戦的萌芽研究)
2013年04月 - 2015年03月
大澤 昌之
日本学術振興会, 競争的資金

皮膚線条はケロイドの対極の病態である！～膠原線維とエストロゲンの知られざる関係
科学研究費助成事業
2012年04月01日 - 2014年03月31日
古川 洋志, 山本 有平, 小山 明彦, 舟山 恵美, 林 利彦, 堀内 勝己, 粛藤 典子
選択的エストロゲン受容体調節薬（SERM、selective estrogen receptor modulator）はエストロゲン受容体に結合し作用するが、受容体の存在する組織によって作動薬または拮抗薬として作用する。SERMのケロイド線維芽細胞に対する効果を検討した。ケロイド線維芽細胞にエストロゲン受容体が存在することを確認し、ケロイド線維芽細胞をSERMで刺激した。SERMは薬剤の種類や濃度によってケロイド線維芽細胞の細胞増殖を抑制する可能性があった。
日本学術振興会, 挑戦的萌芽研究, 北海道大学, 24659777

顔面神経麻痺再建における Ａｃｔｉｖｅ Ａｘｏｎａｌ Ｇｕｉｄａｎｃｅ
科学研究費助成事業
2012年04月01日 - 2014年03月31日
齋藤 亮, 山本 有平, 古川 洋志, 小山 明彦, 舟山 恵美, 大澤 昌之
9週齢のwistar male ratを用いた基礎実験において、顔面神経本幹を切断後に切断端同士を端々神経縫合を行った場合、術後４週において縫合部より軸索再生が起こり、顔面表情筋に達していることが確認できた。また同モデルで神経縫合部にbFGF含浸のMedGelを貼付してcontrol releaseすることにより、軸索再生が促進させることが示唆された。最終的な表情筋の運動もbFGFを作用させた方が改善することが示唆された。これにより、神経断裂後の顔面神経麻痺の治療において、徐放化bFGFが果たす役割が期待される。
日本学術振興会, 挑戦的萌芽研究, 北海道大学, 24659776

リンパ浮腫の外科治療に新展開！～血管柄付リンパ節移植による生体修飾メカニズム探求
科学研究費助成事業
2012年04月01日 - 2014年03月31日
齋藤 典子, 山本 有平, 古川 洋志, 小山 明彦, 舟山 恵美, 齋藤 亮
リンパ浮腫の外科治療の基礎的研究を行った。マウス後肢リンパ浮腫モデルにおいて摘出した膝窩リンパ節部に対側腋窩リンパ節を移植する「リンパ節移植モデル」を開発した。リンパ節を移植したモデルにおいては浮腫の程度の軽減と早期の回復傾向が見られた。
インドシアニングリーンと近赤外線カメラを用いてリンパ流のイメージングを行ったところリンパ節移植モデルにおいて側副路の形成と、移植したリンパ節の生着を示す所見が得られ、これらがリンパ流の回復に寄与しているものと考えられた。
日本学術振興会, 挑戦的萌芽研究, 北海道大学, 24659775

メラノーマ治療成績向上を目指して～ヒアルロン酸修飾インターフェロンβ徐放剤の開発
科学研究費助成事業
2011年04月01日 - 2014年03月31日
齋藤 亮, 山本 有平, 古川 洋志, 小山 明彦, 舟山 恵美, 林 利彦, 田畑 泰彦, 村尾 尚規, 齋藤 典子
亜鉛を介した配位結合により，インターフェロンβとヒアルロン酸が複合体を形成する可能性がある。ラットを用いた生体内実験において複合体形成による徐放効果と考えられる結果を得ることができた。インターフェロンβ，ヒアルロン酸を混合することによりリンパ節に対する徐放効果がある。インターフェロンβをリンパ系を標的に徐放化させることにより，メラノーマの術後補助療法としてのインターフェロンβの効果をより高め，局所の再発とリンパ節転移，あるいはin transit転移を防ぐ有効な治療法となりうる。
日本学術振興会, 基盤研究(B), 北海道大学, 23390406

唇顎口蓋裂治療における再生医学～機能性Ｓｃａｆｆｏｌｄを応用した顎裂再建
科学研究費助成事業
2011年 - 2013年
小山 明彦, 山本 有平, 古川 洋志, 舟山 恵美, 林 利彦, 齋藤 亮, 田畑 泰彦
局所投与されたgranulocyte colony-stimulating factor (G-CSF)が，生体吸収性バイオセラミックスであるbeta-tricalcium phosphate (β-TCP)の骨伝導能を高める作用が認められるか検証した。
ゼラチンハイドロゲルを用いて5μgのG-CSFを徐放化した場合，β-TCPの骨伝導能，生体吸収性の双方を促進する結果が得られた．この徐放化G-CSFとβ-TCPを組み合わせた骨再生法は，頭蓋顎顔面領域の骨欠損治療に対する応用の可能性を有していると考えられる．
日本学術振興会, 挑戦的萌芽研究, 北海道大学, 23659826

ケロイド治療への新たな視点 ～皮膚に対する抗線維化薬の応用～
科学研究費助成事業
2011年 - 2013年
林 利彦, 山本 有平, 古川 洋志, 小山 明彦, 舟山 恵美, 斎藤 亮, 村尾 尚規
ピルフェニドンは特発性肺線維症の治療薬として現在使用されている新しい抗線維化薬である。一方，ケロイドは線維芽細胞の過剰な増殖やα-Smooth muscle Action（α-SMA）や1型コラーゲンなどの過剰な産生といった特徴を持つ皮膚疾患である。本研究では，このケロイド由来の線維芽細胞に対して，ピルフェニドンがどのような作用を持つか実験と検討を行い，新たなケロイド治療薬の可能性を探った。
実験結果からピルフェニドンはケロイド線維芽細胞の細胞増殖と1型コラーゲン産生，α-SMA発現を抑制することが示された。これらの所見からピルフェニドンはケロイド治療に有用である可能性がある。
日本学術振興会, 基盤研究(C), 北海道大学, 23592637

TGF-βの拮抗因子としてのHGF?ケロイド治療の新たな可能性を探る?
科学研究費助成事業
2011年 - 2012年
山本 有平, 古川 洋志, 小山 明彦, 舟山 恵美, 林 利彦, 斎藤 亮
HGF(hepatocytegrowthfactor、肝細胞増殖因子)は肝などの臓器でTGF-β(transforminggrowthfactor-β)に拮抗し線維化を抑制する作用を持つ。HGFはケロイド線維芽細胞においてもTGF-βに拮抗しI型コラーゲンmRNA発現を抑制した。HGFがTGF-βに拮抗する機序の一つとして、TGF-βが受容体に結合して以降の細胞内伝達系を阻害する可能性が考えられた。
日本学術振興会, 挑戦的萌芽研究, 北海道大学, 23659825

ケロイド線維芽細胞の起源を探る-ケモカインに誘導されるfibrocyte-
科学研究費補助金(基盤研究(C))
2010年 - 2012年
舟山 恵美, 山本 有平, 古川 洋志, 小山 明彦, 林 利彦, 齋藤 亮
A)ケロイド組織におけるfibrocyteの存在の有無の確認同意の得られた患者からケロイド組織を採取し,凍結標本,永久標本とした。Fibrocyteの存在の確認のために免疫組織化学染色に使用する抗体を吟味し,CD34の他にLSP-1,pro-collagen Iを用いる方針として,これらを準備した。また,連続切片上でfibrocyteの局在をより詳細に確認するためポドプラニン(リンパ管内皮マーカー),vWF(血管内皮細胞マーカー)等の併用も検討中である。現在,使用する抗体について組み合わせと条件を検討している。上記抗体によってfibroblastとfibrocyteを識別できることを証明するため,患者から採取した組織検体からfibroblastを,血液検体からfibrocyteを培養し,それぞれについて評価を行う方針である。B)ケロイド組織内のケモカインの発現について血管内皮細胞にCXCL12(SDF-1)が発現していたことについて,さらに複数の検体についても染色を行った。血管内皮細胞以外の発現についても現在確認中である。CXCL12と対となるCXCR4についても染色を行ったが,非特異的な所見であったため条件を再検討している。また今後,その他のケモカインとしてCCL3についても染色を行い,組織内のケモカインおよびケモカインレセプターの発現を評価する予定である。なお,上記Aと同...
文部科学省, 基盤研究(C), 北海道大学, 研究代表者, 競争的資金, 22591988

光イメージングによる癌転移機構解明‐メラノーマがリンパから血流に入る瞬間を捉える
科学研究費補助金(基盤研究(B))
2010年 - 2012年
古川 洋志, 山本 有平, 小山 明彦, 舟山 恵美, 林 利彦, 齋藤 亮
【目的】本研究課題は、リンパ節が血流とリンパ流を繋ぐ"道"として作用していることを証明し、その"道"が皮膚癌(その中でも特に悪性黒色腫)の転移にどのように関与しているかを解明することを最終目的としている。そのために、まず今年度は正常なリンパ節の構造と機能をイメージング技術で画像化することを目指した。【方法】研究にはマウスのリンパ節を用いた。まず最初にリンパ節内の血流とリンパ流の分布を調べるために、蛍光物質で標識したゼラチンを血流とリンパ流に乗せて潅流した。蛍光標識ゼラチンは、赤色の蛍光色素と緑色の蛍光色素の2種類を用いて、2色分作成した。一方の蛍光標識ゼラチンをリンパ節の潅流領域の皮下に注射してリンパ流に乗せ、もう一方の蛍光標識ゼラチンを心臓から注入して血流に乗せた。そのリンパ節を摘出した。摘出したリンパ節を薄切し、免疫蛍光染色と組み合わせて蛍光顕微鏡で観察した。【結果】摘出したリンパ節を薄切し、血管およびリンパ洞に対して免疫蛍光染色を行って蛍光顕微鏡で観察したところ、皮下注射した蛍光標識ゼラチンは、リンパ洞内に分布していることが確認できた。同様に心臓から注入した蛍光標識ゼラチンは血管内に分布していることが確認できた。リンパ節内では血流とリンパ流が近接して存在し、お互いに密接に絡み合うように分布していた。2種類の蛍光標識ゼラチンが混ざり合っているところは確認できなかった。【考...
文部科学省, 基盤研究(B), 北海道大学, 連携研究者, 競争的資金, 22390330

運動神経信号付加は本当に起こっているのか?～顔面表情筋mRNA発現変化を捉える～
科学研究費補助金(基盤研究(B))
2010年 - 2012年
山本 有平, 関堂 充, 羽藤 直人, 古川 洋志, 小山 明彦, 舟山 恵美
顔面神経麻痺に対する再建後の運動神経信号の付加が起こっていることを確認するために,顔面表情筋で発現するメッセンジャーRNAであるMyogeninに注目した。Myogeninは筋細胞の分化に重要な役割を果たす遺伝子である。予備的な実験として,ラットを用いて顔面神経本幹を切断したモデルと,切断直後に断端同士を縫合したモデルを作成し,1～28日後の期間,時系列で上口唇の筋肉におけるMyogeninの発現をアガロースゲルによる電気泳動で定量的解析を行い,その後リアルタイムPCRを用いて定量解析を行った。同時に,同じく時系列で眼輪筋の採取を行い,眼輪筋の垂直断面における筋細胞の断面積を測定した。また,逆行性神経トレーサーにより,縫合モデルにおける神経繊維の連続性を確認した。結果,アガロースゲル電気泳動においては両モデルにおいて術直後からMyogeninの発現の上昇が認められ,7～14日後にピークを認めたが,その後発現の低下速度には明らかな差が認められ,切断後縫合モデルにおいてより速やかな発現低下を認めた。又リアルタイムPCRにおいては,切断モデルにおいて術後14日まで発現の上昇が認められた後,速やかに発現の低下が認められたのに対し,切断後縫合モデルにおいては4日で発現がピークを迎え,その後徐々に低下を認めた。更に筋細胞の断面積の解析では切断モデルでは筋萎縮の進行が期間中続いたのに対し,...
文部科学省, 基盤研究(B), 北海道大学, 連携研究者, 競争的資金, 22390331

浸潤型ケロイド細胞は存在するのか!-効率的なケロイド治療を目指して-
科学研究費補助金(基盤研究(B))
2008年 - 2010年
佐々木 了, 林 利彦, 関堂 充, 林 利彦, 山本 有平, 古川 洋志, 小山 明彦, 舟山 恵美, 関堂 充, 堤田 新, 齋藤 亮
活性化し周囲に浸潤するケロイド線維芽細胞周囲にはTリンパ球が浸潤している。活性化したケロイド線維芽細胞は1型コラーゲン産生、TGF-β発現、α-SMA発現が高まっている。よって、ケロイド線維芽細胞とTリンパ球の共培養によりケロイド病態の再現を試みた。結果、Tリンパ球の存在下でケロイド線維芽細胞の1型コラーゲン産生、TGF-β発現はむしろ低下する傾向にあった。Tリンパ球のサブセットによってはケロイド線維芽細胞に対して抑制的にはたらく可能性が示唆された。
文部科学省, 基盤研究(B), 北海道大学, 連携研究者, 競争的資金, 20390454

メラノーマとリンパ管のinteraction-転移促進因子は産生されるのか?-
科学研究費補助金(基盤研究(B))
2008年 - 2010年
堤田 新, 小山 明彦, 齋藤 亮, 浜田 淳一, 山本 有平, 古川 洋志, 舟山 恵美, 林 利彦, 齋藤 亮
本研究では、リンパ管内皮細胞の産生する液性因子が悪性黒色腫細胞の増殖・遊走性に対してどのような影響を及ぼすのかについて調べた。ヒト新生児真皮由来リンパ管内皮細胞の培養上清(LEC-CM)に含まれる悪性黒色腫細胞遊走刺激因子について検討し、その結果、LEC-CMに含まれるラミニン421が悪性黒色腫細胞の遊走性を刺激していることが示唆された。
文部科学省, 基盤研究(B), 北海道大学, 連携研究者, 競争的資金, 20390455

癌のリンパ行性転移の撲滅を目指して～リンパ系ドラッグデリバリーシステムの開発～
科学研究費補助金(基盤研究(B))
2007年 - 2009年
古川 洋志, 関堂 充, 田畑 泰彦, 久下 裕司, 山本 有平, 堤田 新, 舟山 恵美, 林 利彦, 小山 明彦, 田畑 泰彦
本研究では、ゼラチン導入ヒアルロン酸を作成し、これと、近赤外観察カメラを用いたセンチネルリンパ節生検などで近年臨床応用が盛んになされている、インドシアニングリーン(ICG)とを複合体化させることに成功した。本複合体粒子の物性と、実際に動物の体内に投与した場合の動態について検討を行ったところ、複合体化により十分な蛍光強度の増大・持続時間の延長が得られ、ICG単体よりも効率よくリンパ系に分布する可能性が高いことが示唆された。
文部科学省, 基盤研究(B), 北海道大学, 連携研究者, 競争的資金, 19390450