Fujino, Akihiro

写真a

Affiliation

School of Medicine, Department of Surgery (Pediatric Surgery) (Shinanomachi)

Position

Professor

External Links
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Profile 【 Display / hide 】

  • Pediatric surgeon. General, digestive surgery and thoracic surgery in children. In particular, committed to clinical and basic research of lymphatic disease, mainly lymphangioma (lymphatic malformations).

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Career 【 Display / hide 】

  • 2012.04
    -
    Present

    National Center for Child Health and Development, Department of Pediatric Surgery, 非常勤医師

  • 2007.10
    -
    Present

    National Center for Child Health and Development, Reproductive Cell Biology, 共同研究員

  • 2007.07
    -
    2012.03

    National Center for Child Health and Development, Department of Pediatric Surgery, 常勤医師

  • 2005.04
    -
    2007.06

    Massachusetts General Hospital, Pediatric Surgical Research Laboratories, Researcher

  • 2012.04
    -
    Present

    川崎市立川崎病院, 外科, 非常勤医師

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Academic Background 【 Display / hide 】

  • 1990.04
    -
    1996.03

    Keio University, School of Medicine

    University, Graduated

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Academic Degrees 【 Display / hide 】

  • 博士(医学）, Keio University, Dissertation, 2011.09

    Cell migration and activated PI3K/AKT-directed elongation in the developing rat Müllerian duct

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Licenses and Qualifications 【 Display / hide 】

  • 医師免許, 1996.07

  • 日本小児外科学会指導医, 2012.04

  • 日本小児外科学会専門医, 2012.04

  • 日本外科学会外科専門医, 2009.12

  • 日本がん治療認定医機構がん治療認定医, 2013.04

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Research Areas 【 Display / hide 】

  • Life Science / General surgery and pediatric surgery

  • Life Science / Experimental pathology

  • Life Science / Anatomy

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Research Keywords 【 Display / hide 】

  • lymphangioma

  • lymphatic malformation

  • lymphangiomatosis, generalized lymphatic anomaly

  • Müllerrian duct

  • Gorham's disease, Gorham-Stout Syndrome

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Proposed Theme of Joint Research 【 Display / hide 】

  • Regeneration of lymphatic vessel

    Interested in joint research with industry (including private organizations, etc.),  Desired form： Technical Consultation, Cooperative Research

    　View Summary

    The purpose of the research is to overcome lymphatic malformations.

    　View Message

    For lymphatic diseases caused by developmental abnormalities, removal of the lesion and induction of normal lymphatic vessel is required.

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Papers 【 Display / hide 】

  • Comparison of Postoperative Respiratory Function Between Patients After Thoracoscopic and Open Lobectomy

    Ishimaru T., Kanamori Y., Fujino A., Yoneda A., Fujiogi M., Yamamoto Y., Kano M., Koinuma G., Deie K., Kawashima H.

    Journal of Laparoendoscopic and Advanced Surgical Techniques 34 ( 4 ) 376 - 379 2024.04

    ISSN  10926429

    　View Summary

    Purpose: This study aimed to compare respiratory functions of patients after thoracoscopic lobectomy (TS) with those after thoracotomy (TR). Methods: This retrospective study was conducted in two centers, one of which adapted TS as a standard procedure in 2009 and the other performs it via TR. Data on patients who underwent lobectomy for congenital lung disease between 2009 and 2021 and underwent pulmonary function test (spirometry) were collected. Results: Ten patients underwent TS and 36 underwent TR. Distribution based on sex, prenatal diagnosis, pathological diagnosis, and resected lobe were similar between the two groups. The median [interquartile range] age at procedure in the TR group was significantly smaller than that in the TS group (13 [11-18] months versus 38 [13-79] months, P = .03). The procedure duration in the TR group was significantly shorter than that in the TS group (230 [171-264] minutes versus 264 [226-420] minutes, P = .02). Pulmonary function test was conducted at the age of eight in both groups, but the interval between the procedure, and the test was significantly shorter in the TS group (TR: 7 [5-8] years versus TS: 5 [2-7] years, P = .03). The ratio of forced vital capacity compared to predicted one (TR: 86.6 [76.6-95.3] versus TS: 88.7 [86.8-89.1], P = .58) and the ratio of forced expiratory volume in 1 second against that predicted (TR: 84.0 [80.5-88.7] versus TS: 88.7 [86.8-89.1], P = .08) were not significantly different between the two groups. Conclusions: Although TR was performed earlier than TS, respiratory function was similar between the two groups.

  • The Prospective Natural History Study of Patients with Intractable Venous Malformation and Klippel–Trenaunay Syndrome to Guide Designing a Proof-of-Concept Clinical Trial for Novel Therapeutic Intervention

    Fujino A., Kuniyeda K., Nozaki T., Ozeki M., Ohyama T., Sato I., Kamibeppu K., Tanaka A., Uemura N., Kanmuri K., Nakamura K., Kobayashi F., Suenobu S., Nomura T., Hayashi A., Nagao M., Kato A., Aramaki-Hattori N., Imagawa K., Ishikawa K., Ochi J., Horiuchi S., Nagabukuro H.

    Lymphatic Research and Biology 22 ( 1 ) 27 - 36 2024.02

    ISSN  15396851

    　View Summary

    Background: The natural history of venous malformation (VM) and Klippel–Trenaunay Syndrome (KTS) has not been quantitatively studied. To obtain benchmarks to guide designing clinical trials to assess safety and efficacy of novel drug candidates, the clinical course of the patients was followed for 6 months. Methods and Results: This is a multicenter prospective observational study evaluating the change rate in lesion volume from baseline with magnetic resonance images, as the primary endpoint. In addition, disease severities, performance status (PS), pain visual analog scale (VAS) score, quality of life (QoL), infections, and coagulation markers were also evaluated. Thirty-four patients (VM = 17, KTS = 17, 1–53 of age; median 15.9 years) with measurable lesion volume were analyzed. There was no statistically significant difference in the lesion volume between baseline and day 180, and the mean change rate (standard deviation) was 1.06 (0.28). There were no baseline characteristics that affected the change in lesion volume over 6 months. However, there were patients who showed more than 20% volume change and it was suggested that the lesion volume was largely impacted by local infection. There were no statistically significant changes in pain VAS score, severity, PS, QoL score, D-dimer, and platelet count over 6 months within all patients analyzed. Conclusion: The results showed the representative natural course of VM and KTS for a 6-month period with objective change of lesion volume and other factors, suggesting that it is scientifically reasonable to conduct a Phase 2 proof-of-concept study without a placebo arm, using the results of this study as the control.

  • Sirolimus treatment for intractable lymphatic anomalies: an open-label, single-arm, multicenter, prospective trial

    Ozeki M., Endo S., Yasue S., Nozawa A., Asada R., Saito A.M., Hashimoto H., Fujimura T., Yamada Y., Kuroda T., Ueno S., Watanabe S., Nosaka S., Miyasaka M., Umezawa A., Matsuoka K., Maekawa T., Hirakawa S., Furukawa T., Fumino S., Tajiri T., Takemoto J., Souzaki R., Kinoshita Y., Fujino A.

    Frontiers in Medicine 11 2024

    　View Summary

    Introduction: Intractable lymphatic anomalies (LAs) include cystic lymphatic malformation (LM; macrocystic, microcystic, or mixed), generalized lymphatic anomaly, and Gorham–Stout disease. LAs can present with severe symptoms and poor prognosis. Thus, prospective studies for treatments are warranted. We conducted a prospective clinical trial of sirolimus for intractable LAs. Methods: This was an open-label, single-arm, multicenter, prospective trial involving five institutions in Japan. All patients with LAs received oral sirolimus once daily, and the dose was adjusted to ensure that the trough concentration remained within 5–15 ng/mL. We prospectively assessed the drug response (response rate for radiological volumetric change in target lesion), performance state, change in respiratory function, visceral impairment (pleural effusion, ascites, bleeding, pain), laboratory examination data, quality of life (QOL), and safety at 12, 24, and 52 weeks of administration. Results: Eleven patients with LAs (9 generalized lymphatic anomaly, 1 cystic LM, 1 Gorham–Stout disease) were treated with sirolimus, of whom 6 (54.5%; 95% confidence interval: 23.4–83.3%) demonstrated a partial response on radiological examination at 52 weeks of administration. No patients achieved a complete response. At 12 and 24 weeks of administration, 8 patients (72.7%) already showed a partial response. However, patients with stable disease showed minor or no reduction after 12 weeks. Adverse events, such as stomatitis, acneiform dermatitis, diarrhea, and fever, were common with sirolimus. Sirolimus was safe and tolerable. Conclusion: Sirolimus can reduce the lymphatic tissue volume in LAs and may lead to improvements in clinical symptoms and QOL.

  • Evaluation of safety and efficacy of autologous oral mucosa-derived epithelial cell sheet transplantation for prevention of anastomotic restenosis in congenital esophageal atresia and congenital esophageal stenosis

    Fujino A., Fuchimoto Y., Mori T., Kano M., Yamada Y., Ohno M., Baba Y., Isogawa N., Arai K., Yoshioka T., Abe M., Kanai N., Takagi R., Maeda M., Umezawa A.

    Stem Cell Research and Therapy 14 ( 1 )  2023.12

    　View Summary

    Background: We performed the first autologous oral mucosa-derived epithelial cell sheet transplantation therapy in a patient with refractory postoperative anastomotic stricture in congenital esophageal atresia (CEA) and confirmed its safety. In this study, patients with CEA and congenital esophageal stenosis were newly added as subjects to further evaluate the safety and efficacy of cell sheet transplantation therapy. Methods: Epithelial cell sheets were prepared from the oral mucosa of the subjects and transplanted into esophageal tears created by endoscopic balloon dilatation (EBD). The safety of the cell sheets was confirmed by quality control testing, and the safety of the transplantation treatment was confirmed by 48-week follow-up examinations. Results: Subject 1 had a stenosis resected because the frequency of EBD did not decrease after the second transplantation. Histopathological examination of the resected stenosis revealed marked thickening of the submucosal layer. Subjects 2 and 3 did not require EBD for 48 weeks after transplantation, during which time they were able to maintain a normal diet by mouth. Conclusions: Subjects 2 and 3 were free of EBD for a long period of time after transplantation, confirming that cell sheet transplantation therapy is clearly effective in some cases. In the future, it is necessary to study more cases; develop new technologies such as an objective index to evaluate the efficacy of cell sheet transplantation therapy and a device to achieve more accurate transplantation; identify cases in which the current therapy is effective; and find the optimal timing of transplantation; and clarify the mechanism by which the current therapy improves stenosis. Trial registration: UMIN, UMIN000034566, registered 19 October 2018, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000039393.

  • Historical Cohort Study of Congenital Isolated Hypoganglionosis of the Intestine: Determining the Best Surgical Interventions

    Yamada Y., Mori T., Takahashi N., Fujimura T., Kano M., Kato M., Takahashi M., Shimojima N., Watanabe T., Yoshioka T., Kanamori Y., Kuroda T., Fujino A.

    Biomolecules 13 ( 10 )  2023.10

    　View Summary

    No standard diagnostic method or surgical treatment for congenital isolated hypoganglionosis (CIHG) has been established. This study aimed to analyze the clinical outcomes of patients with CIHG and identify the best surgical interventions provided thus far. Data on surgical interventions in 19 patients were collected between 1992 and 2020, including the type of enterostomy, type of revision, and length of the intestines. Ganglion cells in the myenteric plexus were enumerated using Hu C/D staining. The ratio of the length of the small intestine to its height was defined as the intestinal ratio (IR). The outcomes were assessed using the stoma output, growth parameters including the body mass index (BMI), and parenteral nutrition (PN) dependency. All patients required a diverting enterostomy. The IR ranged from 0.51 to 1.75 after multiple non-transplant surgeries. The stoma types were tube-stoma, end-stoma, Santulli-type, and Bishop–Koop (BK)-type. Patients with Santulli- or BK-type stomas had better BMIs and less PN dependency in terms of volume than those with end-stomas or tube-stomas. Two patients with BK-type stomas were off PN, and three who underwent an intestinal transplantation (Itx) achieved enteral autonomy. The management of CIHG involves a precise diagnosis using Hu C/D staining, neonatal enterostomy, and stoma revision using the adjusted IR and Itx if other treatments do not enable enteral autonomy.

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Papers, etc., Registered in KOARA 【 Display / hide 】

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Reviews, Commentaries, etc. 【 Display / hide 】

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Presentations 【 Display / hide 】

  • 肝巨大血管腫　全国調査から標準化治療へ

    Fujino Akihiro

    第31回日本小児外科学会秋季シンポジウム, 

    2015.10
    , 

    Oral presentation (invited, special)

  • リンパ管腫（嚢胞性リンパ管奇形）の治療標準化について

    Fujino Akihiro

    第31回日本小児外科学会秋季シンポジウム (熊本) , 

    2015.10
    , 

    Symposium, workshop panel (nominated), 日本小児外科学会

  • リンパ管腫（リンパ管奇形）とリンパ管腫症に対する新しい薬物療法の選択肢

    Fujino Akihiro

    第31回日本小児外科学会秋季シンポジウム, 

    2015.10
    , 

    Oral presentation (invited, special)

  • 難治性胸腹水を呈するリンパ管関連疾患の外科的治療

    Fujino Akihiro

    第31回日本小児外科学会秋季シンポジウム, 

    2015.10
    , 

    Oral presentation (general)

  • 日本のリンパ管腫患者に対する硬化療法の検討－平成21-23年度厚生労働省難治性疾患克服研究事業結果報告－

    Fujino Akihiro

    第31回日本小児外科学会秋季シンポジウム (熊本) , 

    2015.10
    , 

    Oral presentation (general), 日本小児外科学会

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Research Projects of Competitive Funds, etc. 【 Display / hide 】

  • Biological analysis for elucidation of pathogenesis of lymphangioma using human and mouse lymphangioma model

    2015.04
    -
    2019.03

    Grant-in-Aid for Scientific Research, Research grant, Principal investigator

  • Research for establishing clinical guidelines, and for the clinical application of pathological and cell biological findings of congenital lymphatic diseases

    2014.06
    -
    Present

    日本医療研究開発機構, Health and Labour Sciences Research Grants, Research grant, Principal investigator

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Awards 【 Display / hide 】

  • Best Poster Award at the 4th World Congress of the WOFAPS 2013

    2013.10, The World Federation of Associations of Pediatric Surgeons, The clinical criteria for 'intractable' lymphangioma led by Japanese pediatric surgeons

    Type of Award： International academic award (Japan or overseas)

  • 平成23年度刀林賞

    2012.06, 慶應義塾大学医学部外科同窓会, リンパ管腫内リンパ液動態の検討

    Type of Award： Keio commendation etc.

    　View Description

    リンパ管腫内リンパ液動態の検討

  • 第45回日本小児外科学会学術集会　ベストポスター会長賞

    2008.05, The Japanese Society of Pediatric Surgeons, ヒトリンパ管腫モデル動物の作成

    Type of Award： Award from Japanese society, conference, symposium, etc.

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Courses Taught 【 Display / hide 】

  • SURGERY: SEMINAR

    2024

  • SURGERY: PRACTICE

    2024

  • SURGERY

    2024

  • PATHOPHYSIOLOGICAL ISSUES IN ACUTE CARE

    2024

  • LECTURE SERIES, SURGERY

    2024

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Courses Previously Taught 【 Display / hide 】

  • 外科学（小児）

    Keio University

    2015.04
    -
    2016.03
    , 

    Spring Semester

  • Pediatric Surgery

    Keio University

    2015.04
    -
    2016.03
    , 

    Spring Semester, Lecture, Within own ｆaculty, 1h, 100people

    pediatric surgery

  • Pediatric Surgery

    Keio University

    2013.04
    -
    2014.03
    , 

    Spring Semester, Lecture, Within own ｆaculty, 1h, 100people

    pediatric surgery

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Memberships in Academic Societies 【 Display / hide 】

  • The Japanese Society of Pediatric Surgeons, 

    1999
    -
    Present

  • Japan Surgical Society, 

    1996
    -
    Present

  • Japanese Society of Pediatric Hematology/ Oncology, 

    2002
    -
    Present

  • The Japanese Society of Lymphology, 

    2008
    -
    Present

  • Japanese Society of Emergency Pediatrics, 

    2014
    -
    Present

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Committee Experiences 【 Display / hide 】

  • 2015.08
    -
    Present

    規約委員会, 特定非営利活動法人　日本小外科学会

  • 2015.08
    -
    Present

    庶務委員会, 特定非営利活動法人　日本小児外科学会

  • 2015.04
    -
    Present

    自動車乗車中の子どもの安全推進合同委員会, 特例社団法人　日本小児保健協会

  • 2014.11
    -
    Present

    邦文誌編集委員会, 一般社団法人　日本外科学会

  • 2013
    -
    Present

    データベース委員会, 特定非営利活動法人　日本小児外科学会

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