Updated on 2021/10/26

写真a

 
HINOKI Akinari
 
Organization
Graduate School of Medicine Department of Rare/ Intractable Cancer Analysis Research Industry-Academia Collaborative Chair Designated professor
Title
Designated professor
External link

Degree 1

  1. 博士(医学) ( 2006.10   埼玉医科大学 ) 

Research Interests 6

  1. 小児外科

  2. 小児がん

  3. 希少性・難治性がん

  4. 医療機器

  5. 低侵襲手術

  6. Urine Metabolites

Current Research Project and SDGs 1

  1. Development of new diagnostic techniques for rare and refractory cancers

Education 1

  1. Saitama Medical University

    1992.4 - 1998.3

Professional Memberships 4

  1. 日本外科感染症学会

  2. 日本内視鏡外科学会

  3. 日本小児科学会   評議員

  4. 日本外科学会

Committee Memberships 3

  1. 日本小児外科学会   医薬品・医療機器検討委員会  

    2021.6   

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    Committee type:Academic society

  2. 独立行政法人医薬品医療機器総合機構(PMDA)   専門委員  

    2020.4   

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    Committee type:Government

  3. 日本小児外科学会   保険診療委員会  

    2016.6 - 2018.5   

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    Committee type:Academic society

 

Papers 82

  1. Single-incision laparoscopic percutaneous extraperitoneal closure (SILPEC) for inguinal hernia with prolapsed ovary. Reviewed

    Shirota C, Tainaka T, Sumida W, Yokota K, Makita S, Amano H, Okamoto M, Takimoto A, Yasui A, Nakagawa Y, Hinoki A, Uchida H

    Surgical endoscopy     2021.10

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    Language:English   Publisher:Surgical Endoscopy  

    Background: Most studies reporting the outcomes of laparoscopic ovarian prolapsed hernia operations with large sample sizes are based on intracorporeal closure, while studies on extraperitoneal closure have limited sample sizes. We proactively used the single-incision laparoscopic percutaneous extraperitoneal closure (SILPEC) technique and obtained favorable outcomes, which we report in this paper. Methods: We retrospectively reviewed patients who had undergone laparoscopic surgery for inguinal hernia at our institution. They were retrospectively classified into two groups based on the pre- or intraoperative diagnosis of hernia with a prolapsed ovary, namely the prolapse group and the non-prolapse group, respectively. The data were statistically analyzed and p < 0.05 was considered statistically significant. Results: A total of 771 subjects underwent SILPEC during the study period, including 400 girls. Among them, 63 girls were diagnosed with an ovarian prolapsed hernia. SILPEC was successfully performed through a single port in all cases, with a single exception, in whom the forceps was inserted directly through the right lower quadrant to pull up the ovary. The duration of surgery in the prolapse group was not higher than that in the non-prolapse group. During the SILPEC surgery, the ovaries were successfully reverted into the abdominal cavity by external compression of the inguinal area alone in 38 of the 63 patients. In the remaining 25 cases, the ovaries were reverted into the abdominal cavity by external compression of the inguinal area and traction of the round ligament with forceps. None of these cases failed to return to the ovaries. Conclusion: Our study results indicate that SILPEC may be performed safely for the treatment of ovarian prolapsed inguinal hernia. Since the ovary and fallopian tube are close to the internal inguinal ring due to the short round ligament, the procedure requires careful suturing with traction of the round ligament.

    DOI: 10.1007/s00464-021-08777-4

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  2. An imaging study on tracheomalacia in infants with esophageal atresia: the degree of tracheal compression by the brachiocephalic artery is a good indicator for therapeutic intervention Reviewed

    Sumida Wataru, Tainaka Takahisa, Shirota Chiyoe, Yokota Kazuki, Makita Satoshi, Takimoto Aitaro, Yasui Akihiro, Okamoto Masamune, Nakagawa Yoichi, Hinoki Akinari, Uchida Hiroo

    PEDIATRIC SURGERY INTERNATIONAL     2021.8

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    Language:Japanese   Publisher:Pediatric Surgery International  

    Purpose: Tracheomalacia (TM) is a frequent complication after esophageal atresia (EA) repair. This study aimed to review patients who underwent aortopexy for TM after EA repair and to compare their imaging features. Methods: The patients who underwent thoracoscopic EA repair and contrast-enhanced computed tomography (CECT) at our hospital between 2013 and 2020 were retrospectively reviewed. The ratio of the lateral and anterior–posterior diameter of the trachea (LAR) where the brachiocephalic artery (BCA) crosses the trachea was defined. The LAR of the patients who underwent CECT for asymptomatic pulmonary disease was set as a normal reference. The Z-score of each LAR was calculated and compared between the patients that did or did not undergo aortopexy. Results: A total of 51 patients represented the controls, 5 patients underwent aortopexy, and 12 patients were discharged without surgery. The mean LARs in the patients who underwent aortopexy, did not undergo aortopexy, and controls were 3.54, 1.54, and 1.15, respectively. The mean Z-score of the aortopexy group was 21.2. After successful aortopexy, each patient’s LAR decreased to < 1.5. Conclusion: Aortopexy was preferred if the trachea was compressed by the BCA. The LAR is a useful indicator for predicting the therapeutic effect of aortopexy.

    DOI: 10.1007/s00383-021-04985-0

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  3. Clinical characteristics and outcomes of the right congenital diaphragmatic hernia compared to the left: a 10-year single-center experience Reviewed

    Okamoto Masamune, Amano Hizuru, Uchida Hiroo, Hinoki Akinari, Tainaka Takahisa, Shirota Chiyoe, Sumida Wataru, Yokota Kazuki, Makita Satoshi, Takimoto Aitaro, Yasui Akihiro, Nakagawa Yoichi

    PEDIATRIC SURGERY INTERNATIONAL     2021.8

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    Language:Japanese   Publisher:Pediatric Surgery International  

    Purpose: The features of right-sided congenital diaphragmatic hernias (RCDHs) are quite different from those of left-sided CDHs (LCDHs). We have summarized the features of RCDHs experienced in our institution. Methods: This retrospective study analyzed the cases of patients with CDH registered at our institution between 2011 and 2020. Defects on each side were compared based on prenatal diagnosis, medical treatment, type of surgery, and outcomes. Results: A total of 101 patients underwent surgery at our institution during the neonatal period, and 11 had RCDHs. RCDHs and LCDHs were significantly different in terms of extracorporeal membrane oxygenation (36% vs. 6%, p = 0.002), patch repair (81% vs. 28%, p < 0.001), recurrence rate (36% vs. 11%, p = 0.022), and length of hospital stay (117 days vs. 51 days, p = 0.012). The severity of the fetal diagnosis did not reflect postnatal severity. All patients with RCDH survived to discharge, and there was no significant difference in survival rate between the right and left sides. Conclusion: Neonates with RCDH required more intensive treatments; however, the survival rate was comparable between RCDH and LCDH. RCDH was significantly different from LCDH and an optimal treatment strategy for RCDHs should be established.

    DOI: 10.1007/s00383-021-04999-8

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  4. Development of a novel diagnostic system for bile duct cancer using urinary metabolites. Reviewed

    Amano Hizuru, Hinoki Akinari, Uchida Hiroo, Yokota Kazuki, Ishigaki Takashi, Sakairi Minoru, Abe Mayumi, Terui Yasushi, Oda Hirohisa, Tainaka Takahisa, Shirota Chiyoe, Sumida Wataru, Makita Satoshi, Takimoto Aitaro, Okamoto Masamune, Yasui Akihiro, Nakagawa Yoichi

    CANCER RESEARCH   Vol. 81 ( 13 )   2021.7

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  5. NOVEL BIOMARKER DISCOVERY FOR CHILDHOOD RHABDOMYOSARCOMA USING URINARY METABOLITES Reviewed

    Amano Hizuru, Hinoki Akinari, Uchida Hiroo, Yokota Kazuki, Ishigaki Takashi, Sakairi Minoru, Abe Mayumi, Terui Yasushi, Oda Hirohisa, Tainaka Takahisa, Shirota Chiyoe, Sumida Wataru, Makita Satoshi, Takimoto Aitaro, Kano Yoko, Okamoto Masamune, Yasui Akihiro, Nakagawa Yoichi

    PEDIATRIC BLOOD & CANCER   Vol. 68   page: S46 - S46   2021.6

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  6. Double-balloon endoscopic retrograde cholangiography can make a reliable diagnosis and good prognosis for postoperative complications of congenital biliary dilatation Reviewed

    Shirota Chiyoe, Kawashima Hiroki, Tainaka Takahisa, Sumida Wataru, Yokota Kazuki, Makita Satoshi, Amano Hizuru, Takimoto Aitaro, Hinoki Akinari, Uchida Hiroo

    SCIENTIFIC REPORTS   Vol. 11 ( 1 ) page: 11052   2021.5

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    Bile duct and anastomotic strictures and intrahepatic stones are common postoperative complications of congenital biliary dilatation (CBD). We performed double-balloon endoscopic retrograde cholangiography (DBERC) for diagnostic and therapeutic purposes after radical surgery. We focused on the effectiveness of DBERC for the treatment of postoperative complications of CBD patients. Bile duct and anastomotic strictures and intrahepatic stones are common postoperative complications of congenital biliary dilatation (CBD). We performed double-balloon endoscopic retrograde cholangiography (DBERC) for diagnostic and therapeutic purposes after radical surgery. We focused on the effectiveness of DBERC for the treatment of postoperative complications of CBD patients. This retrospective study included 28 patients who underwent DBERC (44 procedures) after radical surgery for CBD between January 2011 and December 2019. Strictures were diagnosed as “bile duct strictures” if endoscopy confirmed the presence of bile duct mucosa between the stenotic and anastomotic regions, and as “anastomotic strictures” if the mucosa was absent. The median patient age was 4 (range 0–67) years at the time of primary surgery for CBD and 27.5 (range 8–76) years at the time of DBERC. All anastomotic strictures could be treated with only by 1–2 courses of balloon dilatation of DBERC, while many bile duct strictures (41.2%) needed ≥ 3 treatments, especially those who underwent operative bile duct plasty as the first treatment (83.3%). Although the study was limited by the short follow-up period after DBERC treatment, DBERC is recommended as the first-line treatment for hepatolithiasis associated with biliary and anastomotic strictures in CBD patients, and it can be safely performed multiple times.

    DOI: 10.1038/s41598-021-90550-7

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  7. Novel zinc alloys for biodegradable surgical staples Reviewed

    Amano Hizuru, Miyake Koichi, Hinoki Akinari, Yokota Kazuki, Kinoshita Fumie, Nakazawa Atsuko, Tanaka Yujiro, Seto Yasuhiro, Uchida Hiroo

    WORLD JOURNAL OF CLINICAL CASES   Vol. 8 ( 3 ) page: 504 - 516   2020.2

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  8. Identification and Validation of Novel Non-invasive Biomarkers in Patient Urine Samples for Diagnosis of New and Recurrent Neuroblastoma Reviewed

    Yokota Kazuki, Uchida Hiroo, Hinoki Akinari, Sakairi Minoru, Abe Mayumi, Tanaka Yujiro, Tainaka Takahisa, Shirota Chiyoe, Sumida Wataru, Oshima Kazuo, Makita Satoshi, Takimoto Aitaro, Kano Yoko, Inada Kosuke

    PEDIATRIC BLOOD & CANCER   Vol. 66   page: S106 - S106   2019.12

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  9. Factors associated with bleeding after endoscopic variceal ligation for children. Reviewed International journal

    Shinya Yokoyama, Yoji Ishizu, Masatoshi Ishigami, Takashi Honda, Teiji Kuzuya, Takanori Ito, Akinari Hinoki, Wataru Sumida, Chiyoe Shirota, Takahisa Tainaka, Satoshi Makita, Kazuki Yokota, Hiroo Uchida, Mitsuhiro Fujishiro

    Pediatrics international : official journal of the Japan Pediatric Society   Vol. 63 ( 10 ) page: 1223 - 1229   2021.10

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    BACKGROUND: Endoscopic variceal ligation (EVL) is a widely accepted treatment for esophagogastric varices in patients with portal hypertension. It is used for urgent treatment and prophylactic treatment of esophagogastric varices not only in adults, but also in pediatric patients. However, major life-threatening adverse events such as early rebleeding can occur. Although early rebleeding after EVL among children and adolescents has been reported, the risk factors remain obscure. This study evaluated the risk factors for early rebleeding after EVL in children and adolescents. METHODS: Subjects were children and adolescents with portal hypertension aged less than 18 years who underwent EVL for esophagogastric varices. Early rebleeding was defined as hematemesis, active bleeding or blood retention in the stomach, confirmed by esophagogastroduodenoscopy from 2 hours to 5 days after EVL. RESULTS: A total of 50 EVL sessions on 22 patients were eligible for this study. There were 4 episodes of early rebleeding. No other major adverse events have occurred. Multivariate analysis showed that EVL implemented at cardiac varices just below the esophagogastric junction (EGJ); within 5mm from the EGJ, is the independent factor of higher risk of early rebleeding: odds ratio 18.2 (95% Confidence interval: 1.40-237.0), p=0.02. CONCLUSIONS: Children and adolescents who undergo EVL for cardiac varices just below the EGJ have a higher risk of early rebleeding than those who do not.

    DOI: 10.1111/ped.14614

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  10. Late postoperative complications of congenital biliary dilatation in pediatric patients: a single-center experience of managing complications for over 20 years. Reviewed

    Hizuru Amano, Chiyoe Shirota, Takahisa Tainaka, Wataru Sumida, Kazuki Yokota, Satoshi Makita, Aitaro Takimoto, Yujiro Tanaka, Akinari Hinoki, Hiroki Kawashima, Hiroo Uchida

    Surgery today   Vol. 51 ( 9 ) page: 1488 - 1495   2021.9

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    PURPOSE: To investigate late complications after surgery for congenital biliary dilatation (CBD). METHODS: We retrospectively reviewed the patients treated for late postoperative complications of extrahepatic bile duct resection with bilioenteric anastomosis for CBD at our hospital between 1999 and 2019. RESULTS: Twenty-seven complications, including bile duct stenosis with (n = 19) or without (n = 3) hepatolithiasis, remnant intrapancreatic bile duct (n = 2), intestinal obstruction (n = 2), and refractory cholangitis (n = 1) were treated in 26 patients. The median age at radical surgery and the initial treatment of complications was 3 years, 2 months and 14 years, 5 months, respectively. The median period from radical surgery to initial treatment of complications was 7 years, 1 month. Before 2013, bile duct stenosis was initially treated with bile duct plasty (n = 11) or hepatectomy (n = 3), and 71.4% (n = 10) of patients needed further treatment; after 2013, double-balloon endoscopic retrograde cholangiography (DBERC) was used (n = 8), and 25% (n = 2) of patients needed further treatment. Patients with remnant intrapancreatic bile duct, intestinal obstruction, and refractory cholangitis required surgery. CONCLUSION: Long-term follow-up is necessary after surgery for congenital biliary dilatation. DBERC is thus considered to be useful for bile duct stenosis management.

    DOI: 10.1007/s00595-021-02238-0

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  11. Urinary N1,N12-diacetylspermine as a biomarker for pediatric cancer: a case-control study. Reviewed International journal

    Kazuki Yokota, Akinari Hinoki, Kyoko Hiramatsu, Hizuru Amano, Machiko Kawamura, Yachiyo Kuwatsuka, Takahisa Tainaka, Chiyoe Shirota, Wataru Sumida, Satoshi Makita, Masamune Okamoto, Aitaro Takimoto, Akihiro Yasui, Yoichi Nakagawa, Hiroo Uchida, Masao Kawakita

    Pediatric surgery international     2021.8

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    PURPOSE: Minimally invasive examinations are particularly important in pediatric patients. Although the significance of urinary N1,N12-diacetylspermine (DiAcSpm) as a tumor marker (TM) has been reported in many types of adult cancers, its usefulness in pediatric cancers has not been reported. This may be due to urinary DiAcSpm level variations with age. This study aims to measure the normal levels of urinary DiAcSpm in healthy individuals and investigate its usefulness as a TM in childhood cancer. METHODS: Urinary samples were collected from pediatric patients with and without cancer. The urinary DiAcSpm levels were measured, and the values were compared. RESULTS: A total of 32 patients with cancer and 405 controls were enrolled in the study. Of the 32 patients, 13 had neuroblastoma, 9 had malignant lymphoma (ML), and 10 had leukemia. In the control group, the urinary DiAcSpm values markedly fluctuated among those with young age, especially infants; meanwhile, the values converged among those aged roughly 10 years and above. The sensitivity of DiAcSpm was significantly different among the three types of cancers: neuroblastoma (30.8%), ML (77.8%), and leukemia (40%). CONCLUSION: The urinary DiAcSpm value is a useful TM for both screening and follow-up of ML.

    DOI: 10.1007/s00383-021-04987-y

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  12. A patient with very early onset FH-deficient renal cell carcinoma diagnosed at age seven. Reviewed International journal

    Rieko Taniguchi, Hideki Muramatsu, Yusuke Okuno, Taro Yoshida, Manabu Wakamatsu, Motoharu Hamada, Chiyoe Shirota, Wataru Sumida, Akinari Hinoki, Takahisa Tainaka, Yoshimitsu Gotoh, Toyonori Tsuzuki, Yukichi Tanaka, Seiji Kojima, Hiroo Uchida, Yoshiyuki Takahashi

    Familial cancer     2021.6

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    Hereditary leiomyomatosis and renal cell cancer (HLRCC) is caused by heterozygous germline variants in the fumarate hydratase (FH) gene and is associated with increased susceptibility to cutaneous leiomyomas, uterine leiomyomas, and renal cell carcinoma (RCC). HLRCC-associated RCC usually occurs in the middle age, with the median age being 40-44 years. This report describes a seven-year-old (84-month-old) male who developed a large right kidney tumor with multiple cystic lesions that contained enhanced solid components. There was no evidence of distant metastasis. The male patient underwent right nephrectomy and has been recovering well without metastasis or recurrence. Pathological examination revealed that tumor cells with relatively prominent nucleoli and surrounded by halos, were located in a limited area. Immunohistochemical staining was negative for FH. Whole-exome sequencing identified his germline variant in the FH gene and its loss of heterozygosity in the tumor. At nine years (114 months) of age, the male patient showed no recurrence of the tumor. This was the youngest-onset case of HLRCC-associated RCC to date. This report may affect the starting age for future RCC-surveillance programs for patients with HLRCC.

    DOI: 10.1007/s10689-021-00268-8

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  13. Correction to: Postoperative intestinal obstruction in patients with biliary atresia impedes biliary excretion and results in subsequent liver transplantation. Reviewed International journal

    Aitaro Takimoto, Wataru Sumida, Hizuru Amano, Chiyoe Shirota, Takahisa Tainaka, Kazuki Yokota, Satoshi Makita, Akihiro Yasui, Yoko Kanou, Akinari Hinoki, Hiroo Uchida

    Pediatric surgery international   Vol. 37 ( 6 ) page: 835 - 835   2021.6

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  14. Identification of novel neuroblastoma biomarkers in urine samples. Reviewed International journal

    Kazuki Yokota, Hiroo Uchida, Minoru Sakairi, Mayumi Abe, Yujiro Tanaka, Takahisa Tainaka, Chiyoe Shirota, Wataru Sumida, Kazuo Oshima, Satoshi Makita, Hizuru Amano, Akinari Hinoki

    Scientific reports   Vol. 11 ( 1 ) page: 4055 - 4055   2021.2

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    Urine is a complex liquid containing numerous small molecular metabolites. The ability to non-invasively test for cancer biomarkers in urine is especially beneficial for screening child patients. This study attempted to identify neuroblastoma biomarkers by comprehensively analysing urinary metabolite samples from children. A total of 87 urine samples were collected from 54 participants (15 children with neuroblastoma and 39 without cancer) and used to perform a comprehensive analysis. Urine metabolites were extracted using liquid chromatography/mass spectrometry and analysed by Metabolon, Inc. Biomarker candidates were extracted using the Wilcoxon rank sum test, random forest method (RF), and orthogonal partial least squares discriminant analysis (OPLS-DA). RF identified three important metabolic pathways in 15 samples from children with neuroblastoma. One metabolite was selected from each of the three identified pathways and combined to create a biomarker candidate (3-MTS, CTN, and COR) that represented each of the three pathways; using this candidate, all 15 cases were accurately distinguishable from the control group. Two cases in which known biomarkers were negative tested positive using this new biomarker. Furthermore, the predictive value did not decrease in cases with a low therapeutic effect. This approach could be effectively applied to identify biomarkers for other cancer types.

    DOI: 10.1038/s41598-021-83619-w

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  15. Postoperative intestinal obstruction in patients with biliary atresia impedes biliary excretion and results in subsequent liver transplantation. Reviewed International journal

    Aitaro Takimoto, Wataru Sumida, Hizuru Amano, Chiyoe Shirota, Takahisa Tainaka, Kazuki Yokota, Satoshi Makita, Akihiro Yasui, Yoko Kanou, Akinari Hinoki, Hiroo Uchida

    Pediatric surgery international   Vol. 37 ( 2 ) page: 229 - 234   2021.2

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    PURPOSE: This study aimed to investigate the negative effects of intestinal obstruction for jaundice-free native liver survival after Kasai portoenterostomy (PE) for biliary atresia (BA). METHODS: We retrospectively reviewed the records of patients who underwent PE for BA between 2006 and 2019. We evaluated the postoperative morbidity of intestinal obstruction for up to 2 years after PE and the effects of intestinal obstruction on jaundice-free native liver survival. On the basis of their initial operation, patients were divided into open portoenterostomy (Open-PE) and laparoscopic portoenterostomy (Lap-PE) groups, and morbidity was compared. RESULTS: Of the 87 patients reviewed, 6 (6.9%) patients developed postoperative intestinal obstruction and underwent surgery to relieve the obstruction. The morbidity of early postoperative intestinal obstruction was 1.68 per 10,000 person days. The jaundice-free native liver survival rate among patients who once achieved jaundice-free status after PE was significantly lower in the patients with intestinal obstruction compared to in those without intestinal obstruction (0% vs. 73.8%; RR = 3.81, p = 0.007). No significant differences were seen in postoperative intestinal obstructions between the Open-PE and Lap-PE groups (p = 0.242). CONCLUSIONS: Intestinal obstruction negatively impact jaundice-free native liver survival, even in patients who once achieved jaundice-free status after PE for BA.

    DOI: 10.1007/s00383-020-04807-9

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  16. Usefulness of web search queries for early detection of diseases in infants. Reviewed

    Shuji Yamaguchi, Akinari Hinoki, Kota Tsubouchi, Hizuru Amano, Akira Tajima, Hiroo Uchida

    Nagoya journal of medical science   Vol. 83 ( 1 ) page: 107 - 111   2021.2

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    Early detection of diseases is critical in infants. This study evaluates the usefulness of web searches in predicting diseases in order to encourage guardians to consult a doctor promptly if their children are ill. We collected six months of search queries from Yahoo! JAPAN Search between October 2016 and March 2017. Using a machine learning model, we investigated the accuracy of the search query's ability to predict the diagnosis of biliary atresia and hypertrophic pyloric stenosis. Both diseases were modeled with an accuracy of approximately 80%, and symptoms related to the disease were significant features in the model. These findings suggest the possibility of detecting diseases from web search queries performed by guardians. Through future research, we intend to propose a method that uses web search queries for early detection of these diseases by providing appropriate and timely information to support the guardians of patients.

    DOI: 10.18999/nagjms.83.1.107

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  17. Thoracoscopic surgery for congenital lung cysts: an attempt to limit pulmonary resection in cases of lesions involving multiple lobes. Reviewed International journal

    Chiyoe Shirota, Takahisa Tainaka, Wataru Sumida, Kazuki Yokota, Satoshi Makita, Aitaro Takimoto, Hizuru Amano, Akinari Hinoki, Yasuyuki Ono, Hiroo Uchida

    Pediatric surgery international   Vol. 37 ( 2 ) page: 213 - 221   2021.2

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    PURPOSE: Although we generally perform thoracoscopic lobectomy for congenital lung cysts (CLCs), we recently began performing thoracoscopic-limited pulmonary resection (segmentectomy or small partial lung resection) on relatively small lesions and on lesions involving multiple lobes. Our study aimed to determine the therapeutic outcomes of thoracoscopic CLC surgery. METHODS: We retrospectively reviewed patients aged ≤ 18 years who underwent their first CLC surgery at our facility between 2013 and 2020. RESULTS: A comparison between patients < 4 months old and those ≥ 4 months old showed no significant difference in operating time or incidence of complications. Blood loss volume (mL/kg) was significantly greater in patients < 4 months old and in patients who had undergone semi-urgent or urgent surgery. Operating time and postoperative complications were not increased in semi-urgent or urgent surgeries. There was no significant difference in operating time, blood loss volume, or postoperative complications between patients with a preoperative history of pneumonia and patients with no such history. CONCLUSION: In most patients, thoracoscopic surgery for CLC was safely performed. Limited pulmonary resection is considered difficult to perform thoracoscopically in children, but can be safely performed using new devices and navigation methods. LEVEL OF EVIDENCE: III.

    DOI: 10.1007/s00383-020-04793-y

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  18. Risk factors and outcomes of bile leak after laparoscopic surgery for congenital biliary dilatation. Reviewed International journal

    Yujiro Tanaka, Takahisa Tainaka, Akinari Hinoki, Chiyoe Shirota, Wataru Sumida, Kazuki Yokota, Kazuo Oshima, Satoshi Makita, Hizuru Amano, Aitaro Takimoto, Yoko Kano, Hiroo Uchida

    Pediatric surgery international   Vol. 37 ( 2 ) page: 235 - 240   2021.2

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    PURPOSE: One of the main causes of stricture at hepaticojejunostomy site after surgery for congenital biliary dilatation is inflammation or infection associated with bile leak. The aim of this study was to determine the risk factors and outcomes of bile leak after laparoscopic surgery. METHODS: We retrospectively reviewed the demographics and outcomes of patients who underwent laparoscopic surgery for congenital biliary dilatation between September 2013 and December 2019. Data from patients with bile leak were compared to data from patients without bile leak. RESULTS: Fourteen of 78 patients had bile leak. Hepatic duct diameter at anastomosis was the only risk factor of bile leak. Patients with the diameter ≤ 10 mm had higher incidence of bile leak than in patients with the diameter > 10 mm (P = 0.0023). Among them, bile leak occurred more frequently in patients operated on by non-qualified surgeons based on the Japan Society for Endoscopic Surgery endoscopic surgical skill qualification system than by qualified surgeons (P = 0.027). However, none of the patients with bile leak developed anastomotic stricture afterwards. CONCLUSION: Although good technical skill is necessary to avoid bile leak in narrow hepatic duct cases (≤ 10 mm), slight bile leak may not result in anastomotic stricture.

    DOI: 10.1007/s00383-020-04791-0

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  19. A Retrospective Study on the Effect of Surgical Experiences of Laparoscopic Kasai Portenterostomy

    Kurano Yui, Shirota Chiyoe, Hinoki Akinari, Tainaka Takahisa, Sumida Wataru, Yokota Kazuki, Makita Satoshi, Takimoto Aitaro, Uchida Hiroo

    Journal of the Japanese Society of Pediatric Surgeons   Vol. 57 ( 3 ) page: 596 - 599   2021

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    <p><i>Purpose</i>: The treatment outcomes of patients with laparoscopic surgery for biliary atresia (laparoscopic portoenterostomy) were retrospectively evaluated to determine whether to limit the laparoscopic surgery for biliary atresia to fully experienced surgeons.</p><p><i>Methods</i>: We included 37 patients with laparoscopic portoenterostomy for biliary atresia at our institution from 2014 to 2018. Twelve patients were treated by a surgeon fully experienced in laparoscopic portoenterostomy (Group A) and 23 patients were treated by other surgeons (Group B). Jaundice reduction and jaundice-free survival of patients with the native liver in the two groups were compared.</p><p><i>Results</i>: Differences in age at the time of surgery, body weight, perioperative blood loss, time of drain removal, and time that milk or formula feeding resumed in both groups were not significant. The duration of surgery was significantly shorter in Group A than in Group B. The jaundice-free survival rates of patients with the native liver were 58.3% in Group A and 60.9% in Group B at 6 months after surgery, 66.7% in Group A and 65.2% in Group B at 1 year after surgery, and 58.3% in Group A and 56.5% in Group B at 2 years after surgery. No significant difference was observed.</p><p><i>Conclusions</i>: In this study, no significant difference in the rate of jaundice-free survival of patients with the native liver depending on the amount of surgical experience was observed under the guidance of an operator who was skilled in laparoscopic portoenterostomy.</p>

    DOI: 10.11164/jjsps.57.3_596

  20. Intestinal region reconstruction of ileus cases from 3D CT images based on graphical representation and its visualization Reviewed

    Hirohisa Oda, Yuichiro Hayashi, Takayuki Kitasaka, Yudai Tamada, Aitaro Takimoto, Akinari Hinoki, Hiroo Uchida, Kojiro Suzuki, Hayato Itoh, Masahiro Oda, Kensaku Mori

    Medical Imaging 2021: Computer-Aided Diagnosis   Vol. 11597   2021

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    Language:Japanese   Publishing type:Research paper (international conference proceedings)   Publisher:SPIE  

    DOI: 10.1117/12.2581261

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  21. A novel Lugol's iodine staining technique to visualize the upper margin of the surgical anal canal intraoperatively for Hirschsprung disease: a case series. Reviewed International journal

    Kazuki Yokota, Hizuru Amano, Toyoki Kudo, Takeshi Yamamura, Yujiro Tanaka, Takahisa Tainaka, Chiyoe Shirota, Wataru Sumida, Satoshi Makita, Aitaro Takimoto, Masanao Nakamura, Mitsuhiro Fujishiro, Akinari Hinoki, Hiroo Uchida

    BMC surgery   Vol. 20 ( 1 ) page: 317 - 317   2020.12

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    BACKGROUND: In cases of Hirschsprung disease, complete and reproducible resection of the aganglionic bowel is ideal to achieve good postoperative bowel function. Reliable identification of the upper margin of the surgical anal canal, which is the squamous-columnar junction, is necessary during transanal pull-through. Here, we describe a novel staining technique using Lugol's iodine stain to visualize the upper margin of the surgical anal canal. METHODS: Lugol's iodine staining was performed in five patients with Hirschsprung disease treated using a single-stage laparoscopic transanal pull-through modified Swenson procedure. In two of these patients, endocytoscopic observation with ultra-high magnification was performed using methylene blue and crystal violet to mark the border of the squamous epithelium at 1 week before surgery. The alignment between the incisional line, which was revealed using Lugol's iodine staining and endocytoscopic marking, was evaluated. Complications, including postoperative bowel dysfunction, were evaluated. RESULTS: In all cases, Lugol's iodine staining produced a well-demarcated line. The endocytoscopic marking of the upper margin of the surgical anal canal was aligned with the line revealed by Lugol's iodine staining. There were no complications associated with the transanal pull-through procedure, including postoperative bowel dysfunction. CONCLUSIONS: Lugol's iodine staining could be a safe and practical method to visualize the upper margin of the surgical anal canal intraoperatively. This finding may be useful for surgeons to make a consistent removal of the aganglionic bowel during surgery for Hirschsprung disease.

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  22. Laparoscopic Kasai portoenterostomy is advantageous over open Kasai portoenterostomy in subsequent liver transplantation. Reviewed International journal

    Chiyoe Shirota, Naruhiko Murase, Yujiro Tanaka, Yasuhiro Ogura, Masahiro Nakatochi, Hideya Kamei, Nobuhiko Kurata, Akinari Hinoki, Takahisa Tainaka, Wataru Sumida, Kazuki Yokota, Satoshi Makita, Kazuo Oshima, Hiroo Uchida

    Surgical endoscopy   Vol. 34 ( 8 ) page: 3375 - 3381   2020.8

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    BACKGROUND: Native liver survival after laparoscopic Kasai portoenterostomy (Lap-PE) for biliary atresia (BA) is controversial. We examined whether a jaundice-free native liver survival rate is comparable between conventional Kasai portoenterostomy (Open-PE) and Lap-PE. Then, the impact of the two types of PE on subsequent living-donor liver transplantation (LTx) was addressed in this study. METHODS: The jaundice-free rate in 1- and 2-year-old patients who underwent Open-PE and Lap-PE from January 2006 to December 2017 was investigated. Additionally, perioperative data (duration from the start of surgery to the completion of hepatectomy and others) of patients aged 2 years or younger who underwent LTx after either Open-PE or Lap-PE from 2006 to 2017 were evaluated. RESULTS: Thirty-one (67%) out of 46 Open-PE patients and 23 (77%) out of 30 Lap-PE patients showed native liver survival with jaundice-free status at 1 year of age (p = 0.384); 29 (63%) out of 46 Open-PE patients and 19 (70%) out of 27 Lap-PE patients showed native liver survival with jaundice-free status at 2 years of age (p = 0.524); there were no significant differences. Additionally, there were 37 LTx cases after PE within 2 years of birth, including 29 Open-PE and 8 Lap-PE cases. The patients in the Lap-PE group had fewer adhesions and significantly shorter durations of surgery up to the completion of the recipient's hepatectomy and durations of post-LTx hospital stay compared to the Open-PE group. There were no differences in blood loss or duration of stay in intensive care unit between the Lap-PE and Open-PE groups. CONCLUSIONS: Jaundice-free native liver survival rate has been comparable between Open-PE and Lap-PE. Lap-PE resulted in fewer adhesions, contributing to better outcomes of subsequent LTx compared to Open-PE.

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  23. Safe diagnostic management of malignant mediastinal tumors in the presence of respiratory distress: a 10-year experience. Reviewed International journal

    Tomoko Tanaka, Hizuru Amano, Yujiro Tanaka, Yoshiyuki Takahashi, Tatsuro Tajiri, Takahisa Tainaka, Chiyoe Shirota, Wataru Sumida, Kazuki Yokota, Satoshi Makita, Yukiko Tani, Akinari Hinoki, Hiroo Uchida

    BMC pediatrics   Vol. 20 ( 1 ) page: 292 - 292   2020.6

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    BACKGROUND: The fundamental treatment for patients with pediatric malignant mediastinal tumors is chemotherapy. Therefore, accurate diagnosis is essential for selecting the appropriate chemotherapeutic regimen. However, malignant mediastinal tumors occasionally cause respiratory distress, and biopsies under general anesthesia are dangerous for such patients as invasive mechanical ventilation can aggravate airway obstruction caused by mass effect. In this study, we reviewed our 10-year diagnostic experience to evaluate the efficacy of our practices and confirm a safe diagnostic protocol for future patients. METHODS: We retrospectively reviewed medical records of children with malignant mediastinal tumors diagnosed at Nagoya University Hospital from 2007 to 2018 who demonstrated respiratory distress. Respiratory distress included dyspnea, massive pleural effusion, wheezing, and hypoxemia owing to tumors. Data on sex, age at onset, primary symptoms, location of tumor, management strategy (especially the method of diagnosis and definitive diagnosis), clinical course, prognosis during the acute phase (within 3 months from the onset of respiratory symptoms), and long-term outcome were collected. RESULTS: Twelve pediatric patients met the review criteria. There were seven anterior mediastinal tumors and five posterior mediastinal tumors. All anterior mediastinal tumors were diagnosed via bone marrow smear, thoracentesis, or core needle biopsy while maintaining spontaneous breathing. Regarding posterior tumors, two patients were diagnosed via a core needle biopsy and lymph node excisional biopsy under spontaneous breathing. Two cases were initially diagnosed solely using tumor markers. One patient with severe tracheal compression underwent tumor resection with extracorporeal membrane oxygenation stand-by. No patient died of diagnostic procedure-related complications. CONCLUSIONS: In 11 of the 12 cases reviewed, safe and accurate tumor diagnosis was accomplished without general anesthesia. A diagnostic strategy without general anesthesia considering the tumor location proved to be useful.

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  24. 術中膵管損傷に対して内視鏡的に膵管ステントを挿入した1例

    城田 千代栄, 檜 顕成, 内田 広夫, 田井中 貴久, 住田 亙, 横田 一樹, 牧田 智, 天野 日出, 滝本 愛太朗, 安井 昭洋, 石井 宏樹

    日本膵・胆管合流異常研究会プロシーディングス   Vol. 43 ( 0 ) page: 84 - 85   2020

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    DOI: 10.34410/jspbm.43.0_84

  25. 小児腹腔鏡手術における肝内胆管形成術

    田井中 貴久, 内田 広夫, 城田 千代栄, 住田 亙, 横田 一樹, 牧田 智, 滝本 愛太朗, 安井 昭洋, 石井 宏樹, 檜 顕成

    日本膵・胆管合流異常研究会プロシーディングス   Vol. 43 ( 0 ) page: 36 - 36   2020

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  26. Biodegradable Surgical Staple Composed of Magnesium Alloy. Reviewed International journal

    Hizuru Amano, Kotaro Hanada, Akinari Hinoki, Takahisa Tainaka, Chiyoe Shirota, Wataru Sumida, Kazuki Yokota, Naruhiko Murase, Kazuo Oshima, Kosuke Chiba, Yujiro Tanaka, Hiroo Uchida

    Scientific reports   Vol. 9 ( 1 ) page: 14671 - 14671   2019.10

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    Currently, surgical staples are composed of non-biodegradable titanium (Ti) that can cause allergic reactions and interfere with imaging. This paper proposes a novel biodegradable magnesium (Mg) alloy staple and discusses analyses conducted to evaluate its safety and feasibility. Specifically, finite element analysis revealed that the proposed staple has a suitable stress distribution while stapling and maintaining closure. Further, an immersion test using artificial intestinal juice produced satisfactory biodegradable behavior, mechanical durability, and biocompatibility in vitro. Hydrogen resulting from rapid corrosion of Mg was observed in small quantities only in the first week of immersion, and most staples maintained their shapes until at least the fourth week. Further, the tensile force was maintained for more than a week and was reduced to approximately one-half by the fourth week. In addition, the Mg concentration of the intestinal artificial juice was at a low cytotoxic level. In porcine intestinal anastomoses, the Mg alloy staples caused neither technical failure nor such complications as anastomotic leakage, hematoma, or adhesion. No necrosis or serious inflammation reaction was histopathologically recognized. Thus, the proposed Mg alloy staple offers a promising alternative to Ti alloy staples.

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  27. Relationship between Contact Pressure and Motion Artifacts in ECG Measurement with Electrostatic Flocked Electrodes Fabricated on Textile. Reviewed International journal

    Toshihiro Takeshita, Manabu Yoshida, Yusuke Takei, Atsushi Ouchi, Akinari Hinoki, Hiroo Uchida, Takeshi Kobayashi

    Scientific reports   Vol. 9 ( 1 ) page: 5897 - 5897   2019.4

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    To develop a wearable multi-lead electrocardiogram (ECG) measuring system, we fabricated the electrodes and wires by using electrostatic flocking technology on a textile. By using this technology, it was possible to fabricate many electrodes and wires, simultaneously. Also the flocked electrodes and wires had stretchability and washing resistance properties. To use dry electrodes, it is important to reduce the influence of motion artifacts (MAs). The results of the experiment with the skin phantom revealed that the contact pressure between the skin and the electrode is an important factor in MA reduction. Then, we conducted experiments with a human body to determine the relationship between the contact pressure and the MAs. Under the pressures of 200 Pa and 500 Pa, MAs were observed. Meanwhile, under the pressures of 1000 Pa, 2000Pa and 4000 Pa, the ECG signals under rest and deep breathing conditions were able to be measured without MAs. Considering the comfortability, the contact pressure from 1000 Pa to 2000 is preferable. Finally, we fabricated the wearable ECG measuring system and succeeded in measuring 18-lead ECG signals. The measured ECG waveform is in good agreement with the ECG waveform measured by a commercial system.

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  28. A Novel Laparoscopic Surgery Model with a Device to Expand the Abdominal Working Space in Rats: The Influence of Pneumoperitoneum and Skin Incision Length on Postoperative Inflammatory Cytokines. Reviewed International journal

    Naruhiko Murase, Takahisa Tainaka, Hiroo Uchida, Akinari Hinoki, Chiyoe Shirota, Kazuki Yokota, Kazuo Oshima, Ryo Shirotsuki, Kosuke Chiba, Yujiro Tanaka

    Journal of investigative surgery : the official journal of the Academy of Surgical Research   Vol. 32 ( 1 ) page: 55 - 60   2019.1

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    PURPOSE: Experimental models of laparoscopic surgery generally use large animals owing to a sufficient abdominal working space. We developed a novel laparoscopic surgery model in rats. We performed intestinal anastomosis to demonstrate the feasibility and reliability of this model. MATERIALS AND METHODS: We designed a device for rats that expanded the abdominal working space and allowed us to manipulate the intraperitoneal organs by hand under direct vision with pneumoperitoneum. We performed small bowel resection and intestinal anastomosis in rats using this model. To elucidate the effects of pneumoperitoneum and skin incision length, rats were randomly divided into four groups with differing surgical techniques: small incision group, large incision group, small incision + pneumoperitoneum group, and large incision + pneumoperitoneum group. Intraoperative abdominal pressure and postoperative cytokines were measured. RESULTS: One experimenter completed small bowel resection and hand-sewn anastomosis under direct vision without any difficulties or assistance. Carbon dioxide pneumoperitoneum was maintained at 8-10 mmHg during surgery in both pneumoperitoneum groups. Necropsies revealed no evidence of anastomotic leakage at 24 h after surgery. The interleukin-6 and C-reactive protein concentrations were significantly greater in large incision group than in small incision group, but were not significantly different between small incision + pneumoperitoneum group and small incision group. These cytokines concentrations were the greatest in large incision + pneumoperitoneum group. CONCLUSIONS: Our laparoscopic surgery model in rats is a simple and reliable experimental model. The length of skin incision might be a more influential determinant of surgical invasiveness than pneumoperitoneum.

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  29. Multicenter, retrospective, comparative study of laparoscopic and open Kasai portoenterostomy in children with biliary atresia from Japanese high-volume centers. Reviewed

    Naruhiko Murase, Akinari Hinoki, Chiyoe Shirota, Hirofumi Tomita, Naoki Shimojima, Hideyuki Sasaki, Masaki Nio, Kazunori Tahara, Yutaka Kanamori, Masato Shinkai, Hirotoshi Yamamoto, Yasuhiko Sugawara, Taizo Hibi, Tetsuya Ishimaru, Hiroshi Kawashima, Hiroyuki Koga, Atsuyuki Yamataka, Hiroo Uchida

    Journal of hepato-biliary-pancreatic sciences   Vol. 26 ( 1 ) page: 43 - 50   2019.1

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    BACKGROUND: Multicenter study was undertaken to analyze the results of laparoscopic and open Kasai portoenterostomy. METHODS: Subjects were infants with type III biliary atresia who underwent open operation (n = 106) or laparoscopic operation (n = 21) between January 2012 and December 2015. Clinical data were compared between open and laparoscopic operations (2016-0534). Propensity score matching was performed to reduce the effect of treatment selection bias. Multivariate analyses were used to estimate the effect of the surgical approach on the jaundice clearance rate and the native liver survival rate. RESULTS: The postoperative jaundice clearance rate and the 1-year native liver survival rate were not significantly different between open and laparoscopic operations. Rates of cholangitis and major complications of laparoscopic operation were comparable to those of open operation. Blood loss, time to resume oral intake, time to drain removal, and duration of analgesic usage of laparoscopic operation were significantly superior to those of open operation. Similar results were observed when analysis was adjusted based on propensity score. Multivariate analyses demonstrated that only age at operation was a poor prognostic factor. CONCLUSION: Laparoscopic Kasai portoenterostomy was associated with several favorable perioperative outcomes compared with open Kasai portoenterostomy. The difference of surgical approach was not a significant independent predictor.

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  30. Spaciousness Filters for Non-contrast CT Volume Segmentation of the Intestine Region for Emergency Ileus Diagnosis Reviewed

    Hirohisa Oda, Kohei Nishio, Takayuki Kitasaka, Benjamin Villard, Hizuru Amano, Kosuke Chiba, Akinari Hinoki, Hiroo Uchida, Kojiro Suzuki, Hayato Itoh, Masahiro Oda, Kensaku Mori

    Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)   Vol. 11840   page: 104 - 114   2019

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    © 2019, Springer Nature Switzerland AG. This paper proposes enhancement filters for shape-specific regions, based on radial structure tensor (RST) analysis, which we name “spaciousness filters”. RST analysis can be used in a similar way to Hessian analysis for classifying intensity structures. However, RST is insufficient for enhancing regions having little contrast or non-typical morphology. Our proposed filters enhance such regions by extending the ray search scheme of RST analysis to work as a filter evaluating spaciousness. We show applications to the abdominal CT of ileus patients having specific shapes. The intestines (including small intestines) of those patients consist of air, liquid and feces portions, and are not contrast-enhanced by barium. Enhancement of liquid and walls play key roles in the sufficient segmentation of intestines and division between neighboring regions. Experimental results on 7 clinical cases showed that the proposed intestine segmentation method produced higher Dice score (0.68) than traditional RST analysis (0.44), even without specific refinement processes like machine-learning-based false positive reduction.

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  31. Introduction of resection of intrahepatic bile duct stenosis-causing membrane or septum into laparoscopic choledochal cyst excision. Reviewed International journal

    Yujiro Tanaka, Takahisa Tainaka, Wataru Sumida, Akinari Hinoki, Chiyoe Shirota, Naruhiko Murase, Kazuo Oshima, Ryo Shirotsuki, Kosuke Chiba, Hiroo Uchida

    Pediatric surgery international   Vol. 34 ( 10 ) page: 1087 - 1092   2018.10

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    PURPOSE: We previously showed that meticulous probing and resection of the intrahepatic bile duct stenosis (IHBDS)-causing membrane or septum was effective in preventing hepatolithiasis after choledochal cyst excisions in open surgeries. Then, we introduced this maneuver into laparoscopic choledochal cyst excisions in 2014 and performed routine resections since then. The aim of this study was to show the feasibility of this method in laparoscopic surgery. METHODS: We retrospectively reviewed the demographics and outcomes of patients who underwent laparoscopic choledochal cyst excisions at our hospital between January 2014 and December 2017. The patients who underwent surgical treatment for IHBDS-causing membrane or septum were compared with those who did not undergo the procedure. The outcomes of the patients with IHBDS were also compared between patients who were ≥ 3 years of age and those < 3 years at operation. RESULTS: Seventeen of 35 patients underwent laparoscopic resection of IHBDS-causing membrane or septum. There were no complications related to the procedure although the operative time and intraoperative bleeding amount increased in the patients with IHBDS who were ≥ 3 years of age. CONCLUSIONS: Meticulous probing and excision of the IHBDS-causing membrane or septum is safe and feasible during laparoscopic choledochal cyst excision.

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  32. The impact of body weight on stapled anastomosis in pediatric patients. Reviewed International journal

    Hizuru Amano, Yujiro Tanaka, Takahisa Tainaka, Akinari Hinoki, Hiroshi Kawashima, Tomo Kakihara, Kaori Morita, Hiroo Uchida

    Journal of pediatric surgery   Vol. 53 ( 10 ) page: 2036 - 2040   2018.10

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    PURPOSE: The purpose of this study is to clarify the impact of body weight on outcomes of stapled anastomosis in pediatric patients. METHODS: A total of 253 pediatric patients who underwent intestinal anastomosis were classified according to body weight (<3.5 kg: light group, ≥3.5 kg: heavy group), and clinical outcomes of stapled and hand-sewn anastomoses were compared. RESULTS: The light and heavy groups included 77 (stapled: n = 13, hand-sewn: n = 64) and 176 (stapled: n = 58, hand-sewn: n = 118) patients, respectively. In both groups, stapled anastomosis was associated with reduced time to initial oral feeding (light group: 4 vs. 7 days, p = 0.006; heavy group: 3 vs. 5 days, p < 0.001) and full feeding (light group: 12 vs. 16 days, p = 0.026; heavy group: 7 vs. 9 days, p = 0.001), whereas its complication rate was not significantly different from that of hand-sewn anastomosis (light group: 30.8 vs. 12.5%, p = 0.112; heavy group: 3.4 vs. 2.5%, p = 0.665). In patients who underwent stapled anastomosis, the complication rate was significantly higher in the light group (30.8 vs. 3.4%, p = 0.009), with two cases of volvulus related to anastomotic dilatation. CONCLUSIONS: Stapled anastomosis is an effective procedure facilitating prompt oral feeding. However, the risk of complications, including volvulus related to anastomotic dilatation, should be considered among patients weighing <3.5 kg. LEVEL OF EVIDENCE: III.

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  33. Single-stage laparoscopic transanal pull-through modified Swenson procedure without leaving a muscular cuff for short- and long-type Hirschsprung disease: a comparative study. Reviewed International journal

    Kazuki Yokota, Hiroo Uchida, Takahisa Tainaka, Yujiro Tanaka, Chiyoe Shirota, Akinari Hinoki, Takazumi Kato, Wataru Sumida, Kazuo Oshima, Kosuke Chiba, Tetsuya Ishimaru, Hiroshi Kawashima

    Pediatric surgery international   Vol. 34 ( 10 ) page: 1105 - 1110   2018.10

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    PURPOSE: The Soave procedure (SO) is performed most commonly for Hirschsprung disease. SO reduces the risk of injury to the pelvic structures; however, a residual aganglionic muscle cuff could interfere with bowel movement and lead to obstructive enterocolitis. The Swenson procedure is considered ideal in terms of peristalsis. Currently, laparoscopic surgery provides better visualization and facilitates precise dissection, possibly leading to feasible performance of the laparoscopic modified Swenson procedure (SW). We present our operative technique and the efficacy of the SW compared with that of SO. METHODS: We retrospectively reviewed the records of 16 and 27 patients who underwent SW and SO, respectively, between 2012 and 2017. RESULTS: Operative time, blood loss, length of stay, and frequency of bowel movements showed no significant difference between the two groups. In the SW group, temporary dysuria occurred in one patient, postoperative enterocolitis in two, wound infection in one, and severe perianal excoriation in four, whereas in the SO group, obstructive symptoms occurred in three patients, small-bowel obstruction in one, and severe perianal excoriation in three. The complications and outcomes were comparable between both groups. CONCLUSION: Laparoscopic SW was safe and feasible for the short-term follow-up outcomes.

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  34. Oral administration of eicosapentaenoic acid suppresses liver fibrosis in postoperative patients with biliary atresia. Reviewed International journal

    Wataru Sumida, Hiroo Uchida, Takahisa Tainaka, Chiyoe Shirota, Akinari Hinoki, Takazumi Kato, Kazuki Yokota, Kazuo Oshima, Ryo Shirotuki, Kosuke Chiba, Yujiro Tanaka

    Pediatric surgery international   Vol. 34 ( 10 ) page: 1059 - 1063   2018.10

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    PURPOSE: Biliary atresia (BA) is characterized by progressive inflammation of the biliary system. This inflammation persists and causes liver fibrosis, although jaundice disappears after Kasai portoenterostomy (KP). We aimed to confirm whether the oral administration of eicosapentaenoic acid (EPA) suppresses liver fibrosis in postoperative patients with BA. METHODS: We reviewed patients who underwent laparoscopic KP (lapKP) between January 2014 and September 2017. From December 2016, 30 mg/kg/day of EPA was orally administered to patients who opted to take medicine (EPA group). Patients who did not receive EPA were assigned to the non-EPA group. Mac-2 binding protein sugar chain modified isomer (M2BPGi) and hyaluronic acid (HA) levels were compared between the two groups in patients showing disappearance of jaundice at 6 months after the first lapKP. RESULTS: Seventeen patients in the non-EPA group and 11 in the EPA group were enrolled. At 6 months after the first lapKP, 10 patients in the non-EPA group and six in the EPA group were without jaundice. M2BPGi and HA levels were significantly lower in the EPA group. CONCLUSIONS: Liver fibrosis was suppressed in patients without jaundice 6 months after lapKP, who were administered EPA. We believe that periductular inflammation was alleviated by EPA supplementation.

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  35. Long-term outcomes and complications after laparoscopic-assisted anorectoplasty vs. posterior sagittal anorectoplasty for high- and intermediate-type anorectal malformation. Reviewed International journal

    Takahisa Tainaka, Hiroo Uchida, Yujiro Tanaka, Akinari Hinoki, Chiyoe Shirota, Wataru Sumida, Kazuki Yokota, Satoshi Makita, Kazuo Oshima, Kosuke Chiba, Tetsuya Ishimaru, Hiroshi Kawashima

    Pediatric surgery international   Vol. 34 ( 10 ) page: 1111 - 1115   2018.10

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    PURPOSE: Laparoscopic-assisted anorectoplasty (LAARP) is a minimally invasive procedure in which the levator ani muscle is left to potentially improve postoperative fecal continence. This study aimed to retrospectively evaluate postoperative complications and long-term outcomes of fecal continence after LAARP and compare them to those after posterior sagittal anorectoplasty (PSARP). METHODS: Forty-five male patients with high and intermediate anorectal malformation (aged ≥ 4 years) who underwent LAARP or PSARP (LAARP 29, PSARP 16) from 1999 to 2013 were included. Postoperative complications and postoperative fecal continence were retrospectively evaluated and compared. Postoperative complications were also compared before and after introducing a urethroscope during fistula resection. RESULTS: Complications after LAARP and PSARP were seen in 12 vs. 2 cases (p = 0.09) of mucosal prolapse and in 9 vs. 1 case (p = 0.07) of posterior urethral diverticulum (PUD), respectively. The incidence of PUD decreased after introduction of a urethroscopy from 40% in 8/20 cases to 11% in 1/9 cases. No significant difference was found in terms of fecal continence in both groups. CONCLUSION: Through our study, greater improvement of postoperative fecal continence after LAARP has not been shown. LAARP was at higher risk for mucosal prolapse and PUD. However, precise dissection of the urethral fistula could be performed after the introduction of urethroscopy.

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  36. Investigation of the feasibility and safety of single-stage anorectoplasty in neonates with anovestibular fistula. Reviewed International journal

    Chiyoe Shirota, Keisuke Suzuki, Hiroo Uchida, Hiroshi Kawashima, Akinari Hinoki, Takahisa Tainaka, Wataru Sumida, Naruhiko Murase, Kazuo Oshima, Kosuke Chiba, Satoshi Makita, Yujiro Tanaka

    Pediatric surgery international   Vol. 34 ( 10 ) page: 1117 - 1120   2018.10

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    PURPOSE: Anovestibular fistula (AVF) is the most common type of anorectal malformation in females. Delayed anorectoplasty with fistula dilatation is commonly performed during infancy; however, we have been actively performing anorectoplasty in neonates. We report the surgical complications and postoperative defecation function associated with single-stage anorectoplasty performed in neonates. METHODS: Patients who underwent surgery for AVF between 2007 and 2017 at two institutions were retrospectively studied. The operation time, amount of bleeding, time to start oral intake, perioperative complications, and Kelly's score were compared among patients who underwent surgery as neonates and those who underwent surgery as infants. RESULTS: Eighteen neonates and 17 infants underwent anterior sagittal anorectoplasty. The median operation time and time to start oral intake were significantly shorter in the neonatal group (72 min; 3 days, respectively) than in the infant group (110 min, p = 0.0002; 5 days, p = 0.0024, respectively). Postoperative wound disruption was significantly more frequent in the infant group. Of the ten patients each in the neonatal and infant groups, there was no significant difference in Kelly's score at age ≥ 4 years. CONCLUSION: Single-stage anorectoplasty in neonates with AVF can be feasibly performed and does not impair postoperative defecation function. LEVELS OF EVIDENCE: III.

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  37. Development of multi-lead ECG measurement wear using electrostatic flocking technology Reviewed

    T. Takeshita, M. Yosihda, A. Ouchi, A. Hinoki, H. Uchida, T. Kobayashi

    2018 International Conference on Electronics Packaging and iMAPS All Asia Conference, ICEP-IAAC 2018     page: 145 - 146   2018.6

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    We developed textile-based multi-lead ECG measurement wear. The textile-based ECG measurement wear was fabricated by printed electronics and electrostatic flocking technology. We also developed a wireless communication system of multi-lead ECG signals. Moreover, we succeeded to get 18-lead ECG signals around heart using the ECG measurement wear and the wireless measuring system.

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  38. Novel thoracoscopic navigation surgery for neonatal chylothorax using indocyanine-green fluorescent lymphography. Reviewed International journal

    Ryo Shirotsuki, Hiroo Uchida, Yujiro Tanaka, Chiyoe Shirota, Kazuki Yokota, Naruhiko Murase, Akinari Hinoki, Kazuo Oshima, Kosuke Chiba, Wataru Sumida, Masahiro Hayakawa, Takahisa Tainaka

    Journal of pediatric surgery   Vol. 53 ( 6 ) page: 1246 - 1249   2018.6

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    BACKGROUND: Postoperative chylothorax after surgery for esophageal atresia/tracheoesophageal fistula (TEF) is a rare but serious complication, especially in neonates. This study aimed to identify the thoracic duct and ligate chylous leakage sites, using thoracoscopic navigation of an indocyanine-green (ICG)-based near-infrared (NIR) fluorescence imaging system. METHODS: From November 2014 to April 2017, thoracoscopic intraoperative ICG-NIR imaging was performed in 10 newborns (11 surgeries) with first TEF operation or with persistent postoperative chylothorax after TEF operation. NIR imaging was performed 1h after an inter-toe injection of ICG. Thoracoscopic ligations against the NIR-detected leakage sites were performed with sutures. RESULTS: The thoracic duct or lymphatic leakage was directly visualized in each patient. In 8 surgeries with first thoracoscopic TEF operation, one case had suspected minor chylous leakage without postoperative chylothorax. Another case with no chylous leakage at the first operation resulted in chylothorax at postoperative day 11. In three neonates with postoperative chylothorax, leakage points were detected near the ablation site of the azygos vein during the first operation. These points were properly ligated, and postoperative chylous leakage ceased with no adverse events. CONCLUSIONS: Thoracoscopic ICG-NIR imaging encourages the repair of refractory chylothorax and seems reliable. LEVEL OF EVIDENCE: IV.

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  39. Evaluation of Surgical Devices Using an Artificial Pediatric Thoracic Model: A Comparison Between Robot-Assisted Thoracoscopic Suturing Versus Conventional Video-Assisted Thoracoscopic Suturing. Reviewed International journal

    Shinya Takazawa, Tetsuya Ishimaru, Kanako Harada, Kyoichi Deie, Akinari Hinoki, Hiroo Uchida, Naohiko Sugita, Mamoru Mitsuishi, Tadashi Iwanaka, Jun Fujishiro

    Journal of laparoendoscopic & advanced surgical techniques. Part A   Vol. 28 ( 5 ) page: 622 - 627   2018.5

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    BACKGROUND: Pediatric robot-assisted surgery is increasingly being performed, but it is difficult to perform this procedure in infants. A pediatric thoracoscopic model of a 1-year-old patient was developed in our previous study, and this model was used to evaluate the use of a surgical robot for infant surgery. METHODS: Eight pediatric surgeons performed an intracorporeal suturing and knot-tying task using the da Vinci Xi Robotic Surgical System. The task completion time, number of needle manipulations, and force applied during suturing of the robot-assisted thoracoscopic surgery (RATS) group were compared with those of the video-assisted thoracoscopic surgery (VATS) group whose data had been collected from the same 8 surgeons in our previous study. RESULTS: The RATS group showed a significantly shorter completion time than the VATS group in the knot-tying phase (P = .016) and in the total phase (P = .0078). The RATS group showed a significantly smaller number of manipulations than the VATS group in the total phase (P = .039). The RATS group showed a significantly smaller pushing force index than the VATS group in the suturing phase (P = .031), knot-tying phase (P = .031), and in the total phase (P = .031). A seventh rib in the model was dislocated in all RATS group cases. CONCLUSIONS: The da Vinci Surgical System might be useful in infants because of fast movement and small pushing force. However, the robotic 8 mm instruments were too large for use in the thoracic cavity of the 1-year-old infant.

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  40. Usefulness of fetal magnetic resonance imaging for postnatal management of congenital lung cysts: prediction of probability for emergency surgery. Reviewed International journal

    Chiyoe Shirota, Takahisa Tainaka, Toshiki Nakane, Yujiro Tanaka, Akinari Hinoki, Wataru Sumida, Naruhiko Murase, Kazuo Oshima, Kosuke Chiba, Ryo Shirotsuki, Hiroo Uchida

    BMC pediatrics   Vol. 18 ( 1 ) page: 105 - 105   2018.3

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    BACKGROUND: Emergency rescue lung resection is rarely performed to treat congenital lung cysts (CLCs) in neonates. Many reports have described fetal CLC treatment; however, prenatal predictors for postnatal respiratory failure have not been characterized. We hypothesized that fetal imaging findings are useful predictors of emergency surgery. METHODS: We retrospectively studied patients with CLC who underwent lung surgery during the neonatal period in our hospital between January 2001 and December 2015. The demographic data, fetal imaging findings, and intra- and postoperative courses of patients who underwent emergency surgery (Em group) were compared with those of patients who received elective surgery, i.e., non-emergency surgery (Ne group). RESULTS: The Em group and Ne group included 7 and 11 patients, respectively. No significant difference was noted in gestational age, time at prenatal diagnosis, birth weight, and body weight at surgery. The volumes of contralateral lung per thoracic volume were significantly smaller in the Em group than in the Ne group (p = 0.0188). Mediastinal compression was more common in the Em group (7/7) than in the Ne group (4/11) (p = 0.0128). CONCLUSIONS: This is the report describing neonatal emergency lobectomy in patients with CLC evaluated by fetal MRI using the lung volume ratio and mediastinal shift. In patients with CLC, mediastinal shift and significant decreases in contralateral lung volumes during the fetal stages are good prenatal predictors of postnatal emergency lung resection.

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  41. BESNet: Boundary-enhanced segmentation of cells in histopathological images Reviewed

    Hirohisa Oda, Holger R. Roth, Kosuke Chiba, Jure Sokolić, Takayuki Kitasaka, Masahiro Oda, Akinari Hinoki, Hiroo Uchida, Julia A. Schnabel, Kensaku Mori

    Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)   Vol. 11071   page: 228 - 236   2018

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    © Springer Nature Switzerland AG 2018. We propose a novel deep learning method called Boundary-Enhanced Segmentation Network (BESNet) for the detection and semantic segmentation of cells on histopathological images. The semantic segmentation of small regions using fully convolutional networks typically suffers from inaccuracies around the boundaries of small structures, like cells, because the probabilities often become blurred. In this work, we propose a new network structure that encodes input images to feature maps similar to U-net but utilizes two decoding paths that restore the original image resolution. One decoding path enhances the boundaries of cells, which can be used to improve the quality of the entire cell segmentation achieved in the other decoding path. We explore two strategies for enhancing the boundaries of cells: (1) skip connections of feature maps, and (2) adaptive weighting of loss functions. In (1), the feature maps from the boundary decoding path are concatenated with the decoding path for entire cell segmentation. In (2), an adaptive weighting of the loss for entire cell segmentation is performed when boundaries are not enhanced strongly, because detecting such parts is difficult. The detection rate of ganglion cells was 80.0% with 1.0 false positives per histopathology slice. The mean Dice index representing segmentation accuracy was 74.0%. BESNet produced a similar detection performance and higher segmentation accuracy than comparable U-net architectures without our modifications.

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  42. The efficacy of resection of intrahepatic bile duct stenosis-causing membrane or septum for preventing hepatolithiasis after choledochal cyst excision. Reviewed International journal

    Yujiro Tanaka, Takahisa Tainaka, Wataru Sumida, Chiyoe Shirota, Akinari Hinoki, Naruhiko Murase, Kazuo Oshima, Ryo Shirotsuki, Kosuke Chiba, Hiroo Uchida

    Journal of pediatric surgery   Vol. 52 ( 12 ) page: 1930 - 1933   2017.12

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    BACKGROUND/PURPOSE: We previously found that many patients who developed hepatolithiasis after choledochal cyst excisions had intrahepatic bile duct stenosis (IHBDS). In 1992, we started resection of the membrane or septum which was found at the site of IHBDS during choledochal cyst excisions. Since intrahepatic stones usually take years to form, the efficacy of this procedure has not been proved. METHODS: The records of patients who had IHBDS-causing membrane or septum and underwent choledochal cyst excision with Roux-Y hepaticojejunostomy between January 1979 and December 2006 were retrospectively analyzed. The patients who underwent surgical treatment for IHBDS-causing membrane or septum were compared with those who did not undergo the procedure. RESULTS: Sixty-nine patients met the criteria, and seven patients who were followed up for less than 5years were excluded from the study. Thirty-three patients underwent surgical treatment for IHBDS, and three of them developed intrahepatic stones. Meanwhile, 10 of 29 patients who did not undergo the procedure developed intrahepatic stones. A statistically significant difference in intrahepatic stone formation was observed between the two groups in a log-rank test (P=0.016). CONCLUSIONS: Meticulous probing and excision of the IHBDS-causing membrane or septum are effective for preventing hepatolithiasis after choledochal cyst excisions. TYPE OF STUDY: Retrospective Comparative Study. LEVEL OF EVIDENCE: Level III.

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  43. Intralobar pulmonary sequestration expanding toward the contralateral thorax: two case reports. Reviewed International journal

    Hizuru Amano, Jun Fujishiro, Akinari Hinoki, Hiroo Uchida

    BMC surgery   Vol. 17 ( 1 ) page: 110 - 110   2017.11

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    BACKGROUND: Intralobar pulmonary sequestration (ILS) is defined as a portion of parenchyma that is contained within the normal pleural investment of the lung but not connected to the tracheobronchial tree, and supplied by anomalous systemic arteries. As ILS is enveloped within the lobe of the normal lung, it is extremely rare for ILS to invade into the mediastinum. We report two atypical cases of infants with ILS expanded toward the posterior mediastinum and contralateral thorax through the pulmonary ligament. CASE PRESENTATION: The first case involved a baby boy diagnosed at 30 weeks gestation with a cystic area in his right lower lobe. A chest computed tomography (CT) scan at 29 days of life showed low-density masses in the right lower lung and posterior mediastinum. A complete thoracoscopic right lower lobectomy was performed at 19 months of age. After ligation of the aberrant systemic artery, the mediastinal mass was pulled into the right pleural cavity. The mass was observed to connect to the right lower lobe mass as a segment of lung parenchyma situated within the normal pleural investment of the lung, and the patient was diagnosed with ILS. The second case involved the detection by chest CT of a left lower lung cystic mass that protruded into the posterior mediastinum and contralateral chest of a one-month-old baby girl. A complete thoracoscopic left lower lobectomy was performed at the age of 18 months, and the cystic mass located in the right thoracic cavity was pulled easily into the left pleural cavity and resected. An anomalous systemic artery was identified and ligated, and the patient was also diagnosed with ILS. CONCLUSIONS: As the pulmonary ligament consists of two layers of mediastinal pleura, lower lung ILS with its visceral pleura covering can, though rarely, protrude into the mediastinum through the pulmonary ligament. Our two extremely rare cases of infants with ILS expanded toward the posterior mediastinum and contralateral thorax were successfully treated using a unilateral thoracoscopic approach. Pre-surgical differential diagnosis of mediastinal masses using contrast-enhanced multiple detector CT is important in informing the appropriate surgical approach.

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  44. New Navigation Surgery for Resection of Lymphatic Malformations Using Indocyanine Green Fluorescence Imaging

    Shirota Chiyoe, Hinoki Akinari, Takahashi Masataka, Tanaka Yujiro, Tainaka Takahisa, Sumida Wataru, Murase Naruhiko, Oshima Kazuo, Shirotsuki Ryo, Chiba Kosuke, Morimoto Yuji, Uchida Hiroo

    AMERICAN JOURNAL OF CASE REPORTS   Vol. 18   2017.5

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  45. New Navigation Surgery for Resection of Lymphatic Malformations Using Indocyanine Green Fluorescence Imaging.

    Shirota C, Hinoki A, Takahashi M, Tanaka Y, Tainaka T, Sumida W, Murase N, Oshima K, Shirotsuki R, Chiba K, Morimoto Y, Uchida H

    The American journal of case reports   Vol. 18   page: 529-531   2017.5

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  46. Laparoscopic resection of neuroblastomas in low- to high-risk patients without image-defined risk factors is safe and feasible. Reviewed International journal

    Chiyoe Shirota, Takahisa Tainaka, Hiroo Uchida, Akinari Hinoki, Kosuke Chiba, Yujiro Tanaka

    BMC pediatrics   Vol. 17 ( 1 ) page: 71 - 71   2017.3

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    BACKGROUND: Several studies have reported that minimally invasive surgery (MIS) might be considered for resecting neuroblastomas without image-defined risk factors (IDRFs); however, there are no studies comparing the outcomes of laparotomy and laparoscopy in IDRF-negative patients. Thus, we investigated the feasibility of laparoscopic surgery and compared the two abovementioned approaches. METHODS: To compare the effects of laparotomy with those of laparoscopy in patients with neuroblastomas without IDRFs, the following items were retrospectively compared: largest tumor dimension, volume of blood loss, time required to initiate postoperative feeding, locoregional recurrence rate, survival, etc. RESULTS: Nine patients without IDRFs (three at low-to-medium risk and six at high risk) underwent laparotomy, and seven patients without IDRFs (two at low-to-medium risk and five at high risk) underwent laparoscopy. Median duration of surgery was 221 (130-304) and 172 (122-253) min in the laparotomy and laparoscopy groups, respectively, showing no significant difference. Median postoperative time required for resuming meal consumption was significantly longer in the laparotomy (4 days; 2-5) group than that in the laparoscopy group (3 days; 2-3; p = 0.023). Median blood loss was significantly higher in the laparotomy group (5 ml/Kg;2.6-16) than that in the laparoscopy group (2.1 ml/Kg;0.1-4.0; P = 0.037). Median follow-up period was 81 (52-94) and 21 (17-28) months, locoregional recurrence rates were 22 and 0% at 1 year, 1-year progression-free survival rates were 78 and 100%, and overall survival rates were 67 and 100% in the laparotomy and laparoscopy groups, respectively, with no significant differences. CONCLUSIONS: MIS for the treatment of neuroblastomas without IDRFs in low- to high-risk patients is safe and feasible and does not compromise the treatment outcome.

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  47. Two-Stage Thoracoscopic Repair of Long-Gap Esophageal Atresia Using Internal Traction Is Safe and Feasible. Reviewed International journal

    Takahisa Tainaka, Hiroo Uchida, Akihide Tanano, Chiyoe Shirota, Akinari Hinoki, Naruhiko Murase, Kazuki Yokota, Kazuo Oshima, Ryo Shirotsuki, Kosuke Chiba, Hizuru Amano, Hiroshi Kawashima, Yujiro Tanaka

    Journal of laparoendoscopic & advanced surgical techniques. Part A   Vol. 27 ( 1 ) page: 71 - 75   2017.1

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    BACKGROUND: The treatment of long-gap esophageal atresia remains an issue for pediatric surgeons. Many techniques for treating long-gap esophageal atresia have been proposed, but the optimal method has not been established. The thoracoscopic esophageal elongation technique has recently been developed. We previously reported a case in which two-stage thoracoscopic repair was performed using internal esophageal traction without esophageal tearing, and we retrospectively reviewed the outcomes of this procedure in this study. METHODS: Five patients underwent thoracoscopic treatment involving internal esophageal traction for esophageal atresia involving a long gap or vascular ring over a 5-year period. RESULTS: Between November 2010 and November 2015, 5 patients were treated with thoracoscopic traction. All of these patients successfully underwent thoracoscopic-delayed primary anastomosis. Conversion to open thoracotomy was not required in any case. The postoperative complications experienced by the patients included minor anastomotic leakage in 2 cases, anastomotic stenosis in 1 case, gastroesophageal reflux (GER) in 4 cases, and a hiatal hernia in 1 case. None of the patients died. CONCLUSIONS: Two-stage thoracoscopic repair for esophageal atresia involving a long gap or vascular ring is a safe and feasible procedure; however, we must develop methods for treating minor anastomotic complications and GER due to esophageal traction in future.

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  48. Left thoracoscopic two-stage repair of tracheoesophageal fistula with a right aortic arch and a vascular ring Reviewed

    Kazuo Oshima, Hiroo Uchida, Takahisa Tainaka, Akihide Tanano, Chiyoe Shirota, Kazuki Yokota, Naruhiko Murase, Ryo Shirotsuki, Kosuke Chiba, Akinari Hinoki

    Journal of Minimal Access Surgery   Vol. 13 ( 1 ) page: 73 - 75   2017

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    © 2017 Journal of Minimal Access Surgery Published by Wolters Kluwer - Medknow. A right aortic arch (RAA) is found in 5% of neonates with tracheoesophageal fistulae (TEF) and may be associated with vascular rings. Oesophageal repairs for TEF with an RAA via the right chest often pose surgical difficulties. We report for the first time in the world a successful two-stage repair by left-sided thoracoscope for TEF with an RAA and a vascular ring. We switched from right to left thoracoscopy after finding an RAA. A proximal oesophageal pouch was hemmed into the vascular ring; therefore, we selected a two-stage repair. The TEF was resected and simple internal traction was placed into the oesophagus at the first stage. Detailed examination showed the patent ductus arteriosus (PDA) completing a vascular ring. The subsequent primary oesophago-oesophagostomy and dissection of PDA was performed by left-sided thoracoscope. Therefore, left thoracoscopic repair is safe and feasible for treating TEF with an RAA and a vascular ring.

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  49. Long-term outcomes after revision of Kasai portoenterostomy for biliary atresia. Reviewed

    Chiyoe Shirota, Hiroo Uchida, Yasuyuki Ono, Naruhiko Murase, Takahisa Tainaka, Kazuki Yokota, Kazuo Oshima, Ryo Shirotsuki, Akinari Hinoki, Hisami Ando

    Journal of hepato-biliary-pancreatic sciences   Vol. 23 ( 11 ) page: 715 - 720   2016.11

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    BACKGROUND: The indications for and efficacy of revision of portoenterostomy (PE) for biliary atresia (BA) needs to be reassessed in an era of liver transplantation. We therefore reviewed the long-term outcomes following revision of PE. METHODS: This was a retrospective study of the medical records of patients with BA who underwent PE and revision of PE. We investigated the role of revision on outcomes of jaundice-free native liver survival (approval number: 2015-0094). RESULTS: Portoenterostomy was performed in 76 patients, among whom 22 underwent revision. Revision for recurrent jaundice was performed for four of 51 patients, who were transiently jaundice free after initial PE, but only one achieved native liver survival. Revision for repeated cholangitis in two patients achieved native liver survival over 10 years. Revision was performed in 16 of the 25 patients in whom initial PE failed; of these, four survived with their native liver (ages 3, 12, 12, and 14 years). The PE revision did not significantly affect liver transplantation duration and survival outcome. CONCLUSIONS: Revision of PE was suitable for repeated cholangitis. Revision for recurrent jaundice, regardless of whether the initial PE was successful, could have a limited but positive effect in preventing long-term progressive liver failure.

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  50. Comparing surgical outcomes of complete thoracoscopic lobectomy for congenital cystic lung disease between neonatal and infantile patients. Reviewed

    Takahisa Tainaka, Hiroo Uchida, Yujiro Tanaka, Chiyoe Shirota, Kazuki Yokota, Naruhiko Murase, Kazuo Oshima, Ryo Shirotsuki, Kosuke Chiba, Akinari Hinoki

    Nagoya journal of medical science   Vol. 78 ( 4 ) page: 447 - 454   2016.11

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    Thoracoscopic lobectomy has recently become a widely used surgical treatment for congenital cystic lung disease, but significant issues can arise in some cases, such as a limited working space in neonates, a limited view in cases involving large cystic lesions. We reviewed the treatment outcomes of neonates that underwent complete thoracoscopic lobectomy or segmentectomy and evaluated the operative difficulties. From January 2008 to October 2015, 38 patients under the age of 1 year underwent complete thoracoscopic lobectomy or segmentectomy for cystic lung disease at our institution. We compared the intra- and postoperative data of the neonate group (N group) with those of the infant group (I group). Fourteen and 24 patients underwent thoracoscopic lobectomy or segmentectomy in the N group and I group, respectively. The operative time and amount of intraoperative blood loss did not differ significantly between the two groups (p=0.694 and p=0.878, respectively), but the duration of the postoperative hospitalization period was significantly longer (p<0.01) in the N group. The frequencies of postoperative complications did not differ significantly between the two groups. The operative time of thoracoscopic lobectomy was significantly longer in cases involving incomplete lobar fissures than in those involving normal lobar fissures. Surgical outcomes of complete thoracoscopic lobectomy for neonatal cases are almost equivalent compared with infantile cases, and thoracoscopic lobectomy takes longer in cases involving incomplete lobar fissures.

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  51. Steroid pulse therapy prevents restenosis following balloon dilatation for esophageal stricture. Reviewed International journal

    Kazuki Yokota, Hiroo Uchida, Akihide Tanano, Chiyoe Shirota, Takahisa Tainaka, Akinari Hinoki, Naruhiko Murase, Kazuo Oshima, Ryo Shirotsuki, Kosuke Chiba

    Pediatric surgery international   Vol. 32 ( 9 ) page: 875 - 879   2016.9

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    PURPOSE: This study aimed to evaluate the effectiveness of intravenous steroid pulse therapy following balloon dilatation for esophageal stenosis and stricture in children. METHODS: The study enrolled six children, including three with congenital esophageal stenosis and three with anastomotic strictures after surgery for esophageal atresia, all of whom were treated by balloon dilatation combined with high-dose intravenous methylprednisolone pulse therapy. Methylprednisolone was injected intravenously at a dose of 20 mg/kg/day for 2 days, starting from the day of dilatation, followed by 10 mg/kg/day for 2 days, for a total of 4 days. RESULTS: Esophageal stricture recurred in all three patients with congenital esophageal stenosis despite repeated balloon dilatation without methylprednisolone. However, the symptoms of dysphagia improved and did not recur after systemic steroid pulse therapy following balloon dilatation. Symptoms also resolved in all three patients with anastomotic strictures following balloon dilatation with systemic steroid pulse therapy. All six patients remained asymptomatic after 6-21 months follow-up, with no complications. CONCLUSION: Intravenous methylprednisolone pulse therapy following balloon dilatation is safe and effective for the treatment of esophageal stenosis and strictures in children.

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  52. Polylactic acid nanosheets in prevention of postoperative intestinal adhesion and their effects on bacterial propagation in an experimental model. Reviewed International journal

    A Hinoki, A Saito, M Kinoshita, J Yamamoto, D Saitoh, S Takeoka

    The British journal of surgery   Vol. 103 ( 6 ) page: 692 - 700   2016.5

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    BACKGROUND: Ultrathin films (nanosheets) adhere tightly to organ surfaces but prevent adhesion to other organs. The antiadhesive effect of nanosheets and their effect on bacterial propagation were investigated in a murine intestinal adhesion model. METHODS: Polylactic acid nanosheets (approximately 80 nm thick) were produced. Serosal defects were created by peeling off the intestinal serosa; these were left open or covered with nanosheets or Seprafilm® and the formation of intestinal adhesions was analysed. To examine bacterial propagation, a nanosheet or Seprafilm® was placed on intact murine jejunum followed by Escherichia coli inoculation at the site. RESULTS: Treatment both with nanosheets and with Seprafilm® reduced postoperative intestinal adhesion (mean adhesion score 0·67 for nanosheets, 0·43 for Seprafilm® and 2·87 for no antiadhesive treatment; P < 0·001 for nanosheets or Seprafilm® versus no adhesive treatment). Nanosheet treatment did not affect bacterial propagation in the peritoneal cavity, whereas Seprafilm®-treated mice showed bacterial propagation, leading to increased mortality. CONCLUSION: Nanosheets may be effective novel antiadhesive agents even in the presence of bacterial contamination. Surgical relevance Intra-abdominal adhesions following surgical contamination can trigger postoperative complications and lead to deterioration in long-term quality of life. However, currently there are no effective antiadhesion materials to prevent the formation of adhesions. Treatment with ultrathin nanosheets effectively reduced postoperative intestinal adhesion in an experimental mouse model, and did not affect bacterial propagation in the peritoneal cavity. These nanosheets are potent novel antiadhesive materials that potentially can be applied even in contaminated conditions.

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  53. In vivo estimation of optical properties of rat liver using single-reflectance fiber probe during ischemia and reperfusion Reviewed

    Sharmin Akter, Tomoki Tanabe, Satoshi Maejima, Satoko Kawauchi, Shunichi Sato, Akinari Hinoki, Suefumi Aosasa, Junji Yamamoto, Izumi Nishidate

    OPTICAL REVIEW   Vol. 23 ( 2 ) page: 354 - 359   2016.4

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    To quantify the changes in optical properties of in vivo rat liver tissue, we applied diffuse reflectance spectroscopy (DRS) system using single-reflectance fiber probe during ischemia and reperfusion evoked by hepatic portal occlusion (hepatic artery, portal vein and bile duct). Changes in the reduced scattering coefficient mu(s)', the absorption coefficient mu(a), the tissue oxygen saturation StO(2), and the oxidation of heme aa3 in cytochrome c oxidase (CcO) OHaa(3) of in vivo rat liver (n = 6) were evaluated. Heme aa(3) in CcO were significantly reduced (P &lt; 0.05) during ischemia, which indicates a sign of mitochondrial energy failure induced by oxygen insufficiency of liver tissue. We found that OHaa(3) obtained from the proposed method was unchanged immediately after the onset of ischemia and started gradually decreasing at 2 min after the onset of ischemia. Difference in the time course between OHaa3 and the conventional ratio metric analysis with mu(a)(605)/mu(a)(620) reported in literature demonstrates that the proposed method is effective in reduction of optical cross talk between hemoglobin and heme aa3. Our results suggest that DRS technique is applicable and useful for assessing in vivo tissue viability and hemodynamics in liver intraoperatively.

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  54. Subcutaneous endoscopically assisted ligation using miniport for the treatment of girls with inguinal hernia Reviewed

    Akinari Hinoki, Ikeda Rie, Daiki Kitagawa, Kazuki Koiwai, Takemaru Tanimizu, Kazuo Hase, Shigeki Takahashi

    Annals of Pediatric Surgery   Vol. 12 ( 2 ) page: 73 - 76   2016

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    Background: This report describes the first miniport method using subcutaneous endoscopically assisted ligation (SEAL) for the treatment of girls with inguinal hernia. To validate its safety and efficacy, the authors evaluated their early experiences. Methods: Between April 2014 and December 2014, 19 SEALs using miniport were performed on 14 patients at the Fukaya Red-Cross Hospital, Saitama, Japan. Their mean age was 6 years (range, 11-128 months). This technique was performed using two ports (a 5 mm port placed using the open technique and an additional 2 mm miniport). A 5 mm laparoscope was inserted via the umbilicus. The miniport was introduced percutaneously in the inguinal region under laparoscopic guidance and manipulated around the medial or lateral hemicircumference of the internal ring extraperitoneally to place a purse-string around the internal ring. The hernia sac and patent processus vaginalis were closed at the level of the internal inguinal ring extraperitoneally with circuit suturing using the 2 mm miniport. Only the umbilical fascia was closed with an absorbable suture. No skin sutures were applied. We collected data regarding operative time, complications, and recurrence. Results: The mean operative time was 20±6 min (unilateral, n=9) or 42±8 min (bilateral, n=5). The mean follow-up period was 12.8±2.5 (range, 9-19) months. No intraoperative complications associated with the procedure occurred and no hernial recurrences have been identified so far. Conclusion: SEAL using miniport proved to be a successful operative procedure compared with other laparoscopic percutaneous extraperitoneal closure procedures and produced excellent cosmetic results. SEAL using miniport for the treatment of girls with inguinal hernias appears to be safe, effective, and reliable.

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  55. Single-incision thoracoscopic surgery for spontaneous pneumothorax in a 14-year-old girl Reviewed

    Kazuki Koiwai, Takemaru Tanimizu, Akinari Hinoki, Ryosuke Satake, Daiki Kitagawa, Hiroaki Komuro, Kazuo Hase, Junji Yamamoto

    Annals of Pediatric Surgery   Vol. 12 ( 2 ) page: 71 - 72   2016

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    Single-incision thoracoscopic surgery has become popular because of its potential to further extend the benefits of thoracoscopic surgery, such as less pain, a faster recovery time, and improved cosmesis, but the limited visualization due to crowding of instruments requires a certain amount of skill, especially in children. We herein describe a single-access video-assisted thoracoscopic surgery for a pediatric spontaneous pneumothorax. This procedure was useful, led to less postoperative pain and a better cosmetic appearance, and resulted in satisfactory results.

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  56. Emergency hepatectomy for hepatic arteriovenous malformation combined with pulmonary hypertension in an infant Reviewed

    Naruhiko Murase, Hiroo Uchida, Akihide Tanano, Chiyoe Shirota, Akinari Hinoki, Takahisa Tainaka, Kazuki Yokota, Kazuo Oshima, Ryo Shirotsuki

    Journal of Pediatric Surgery Case Reports   Vol. 3 ( 12 ) page: 534 - 536   2015.12

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:Elsevier Inc.  

    Patients with hepatic arteriovenous malformations rarely present with pulmonary hypertension. We report the case of a 3-month-old boy who developed severe pulmonary hypertension due to a hepatic arteriovenous malformation. The use of pulmonary vasodilators to treat the patient's pulmonary hypertension worsened his high-output heart failure. This is the first case in which emergency hepatectomy rescued a patient with hepatic arteriovenous malformations who developed pulmonary hypertension.

    DOI: 10.1016/j.epsc.2015.10.017

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  57. Evaluation of light scattering and absorption properties of in vivo rat liver using a single-reflectance fiber probe during preischemia, ischemia-reperfusion, and postmortem. Reviewed International journal

    Sharmin Akter, Satoshi Maejima, Satoko Kawauchi, Shunichi Sato, Akinari Hinoki, Suefumi Aosasa, Junji Yamamoto, Izumi Nishidate

    Journal of biomedical optics   Vol. 20 ( 7 ) page: 076010 - 076010   2015.7

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    Diffuse reflectance spectroscopy (DRS) has been extensively used for characterization of biological tissues as a noninvasive optical technique to evaluate the optical properties of tissue. We investigated a method for evaluating the reduced scattering coefficient μ(s)', the absorption coefficient μ(a), the tissue oxygen saturation StO₂, and the reduction of heme aa3 in cytochrome c oxidase CcO of in vivo liver tissue using a single-reflectance fiber probe with two source-collector geometries. We performed in vivo recordings of diffuse reflectance spectra for exposed rat liver during the ischemia-reperfusion induced by the hepatic portal (hepatic artery, portal vein, and bile duct) occlusion. The time courses of μ a at 500, 530, 570, and 584 nm indicated the hemodynamic change in liver tissue as well as StO₂. Significant increase in μ(a)(605)/μ(a)(620) during ischemia and after euthanasia induced by nitrogen breathing was observed, which indicates the reduction of heme aa3, representing a sign of mitochondrial energy failure. The time courses of μ(s)' at 500, 530, 570, and 584 nm were well correlated with those of μ(a), which also reflect the scattering by red blood cells. On the other hand, at 700 and 800 nm, a temporary increase in μ(s)' and an irreversible decrease in μ(s)' were observed during ischemia-reperfusion and after euthanasia induced by nitrogen breathing, respectively. The change in μ(s)' in the near-infrared wavelength region during ischemia is indicative of the morphological changes in the cellular and subcellular structures induced by the ischemia, whereas that after euthanasia implies the hepatocyte vacuolation. The results of the present study indicate the potential application of the current DRS system for evaluating the pathophysiological conditions of in vivo liver tissue.

    DOI: 10.1117/1.JBO.20.7.076010

    PubMed

  58. A repressor protein, Mnt, is a novel negative regulator of vascular smooth muscle cell hypertrophy by angiotensin II and neointimal hyperplasia by arterial injury. Reviewed International journal

    Takehiko Takayanagi, Akito Eguchi, Akira Takaguri, Akinari Hinoki, Allison M Bourne, Katherine J Elliott, Peter J Hurlin, Satoru Eguchi

    Atherosclerosis   Vol. 228 ( 1 ) page: 90 - 3   2013.5

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    OBJECTIVE: The Max-interacting protein Mnt is a transcriptional repressor that can antagonize the transcriptional and proliferation-related activities of Myc. Here, we tested the hypothesis that Mnt is a negative regulator of pathological vascular remodeling. METHODS: Adenovirus encoding Mnt or control GFP was infected to cultured rat vascular smooth muscle cells (VSMC) and carotid arteries after a balloon angioplasty. RESULTS: In VSMC, adenoviral gene transfer of Mnt suppressed angiotensin II-induced protein expression of early growth response protein-1 (Egr1) and its promoter activation. Mnt adenovirus did not interfere with upstream signaling of angiotensin II. Angiotensin II-induced protein accumulation in VSMC was inhibited by Mnt adenovirus. Mnt adenovirus also inhibited platelet-derived growth factor-induced VSMC proliferation. Moreover, Mnt adenovirus prevented neointima formation in response to arterial injury. The adenoviral Mnt gene transfer also prevented Egr1 induction in neointima. CONCLUSION: These data identify Mnt as a previously unrecognized negative regulator of pathological vascular remodeling.

    DOI: 10.1016/j.atherosclerosis.2013.02.033

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  59. A disintegrin and metalloprotease 17 mediates neointimal hyperplasia in vasculature. Reviewed International journal

    Akira Takaguri, Keita Kimura, Akinari Hinoki, Allison M Bourne, Michael V Autieri, Satoru Eguchi

    Hypertension (Dallas, Tex. : 1979)   Vol. 57 ( 4 ) page: 841 - 5   2011.4

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    The requirement of a metalloprotease, a disintegrin and metalloprotease 17 (ADAM17) for the growth of cultured vascular smooth muscle cells has been demonstrated in vitro. However, whether this metalloprotease is responsible for vascular remodeling in vivo remains unanswered. Rat carotid arteries were analyzed 2 weeks after a balloon angioplasty. The neointimal cells were strongly positive for ADAM17 immunostaining. Marked inhibition of intimal hyperplasia was observed in a dominant-negative ADAM17 adenovirus-treated carotid artery. Proliferating cell nuclear antigen-positive cells and phospho-epidermal growth factor receptor-positive cells in the neointima were reduced by dominant-negative ADAM17 as well. In contrast, the neointima formation, proliferating cell nuclear antigen-positive cells, and phospho-epidermal growth factor receptor-positive cells were markedly enhanced by wild-type ADAM17 adenovirus. In conclusion, ADAM17 activation is involved in epidermal growth factor receptor activation and subsequent neointimal hyperplasia after vascular injury. ADAM17 could be a novel therapeutic target for pathophysiological vascular remodeling.

    DOI: 10.1161/HYPERTENSIONAHA.110.166892

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  60. Caveolin-1 negatively regulates a metalloprotease-dependent epidermal growth factor receptor transactivation by angiotensin II. Reviewed International journal

    Akira Takaguri, Heigoro Shirai, Keita Kimura, Akinari Hinoki, Kunie Eguchi, MaryEllen Carlile-Klusacek, Baohua Yang, Victor Rizzo, Satoru Eguchi

    Journal of molecular and cellular cardiology   Vol. 50 ( 3 ) page: 545 - 51   2011.3

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    A metalloprotease, ADAM17, mediates the generation of mature ligands for the epidermal growth factor receptor (EGFR). This is the key signaling step by which angiotensin II (AngII) induces EGFR transactivation leading to hypertrophy and migration of vascular smooth muscle cells (VSMCs). However, the regulatory mechanism of ADAM17 activity remains largely unclear. Here we hypothesized that caveolin-1 (Cav1), the major structural protein of a caveolae, a membrane microdomain, is involved in the regulation of ADAM17. In cultured VSMCs, infection of adenovirus encoding Cav1 markedly inhibited AngII-induced EGFR ligand shedding, EGFR transactivation, ERK activation, hypertrophy and migration, but not intracellular Ca(2+) elevation. Methyl-β-cyclodextrin and filipin, reagents that disrupt raft structure, both stimulated an EGFR ligand shedding and EGFR transactivation in VSMCs. In addition, non-detergent sucrose gradient membrane fractionations revealed that ADAM17 cofractionated with Cav1 in lipid rafts. These results suggest that lipid rafts and perhaps caveolae provide a negative regulatory environment for EGFR transactivation linked to vascular remodeling induced by AngII. These novel findings may provide important information to target cardiovascular diseases under the enhanced renin angiotensin system.

    DOI: 10.1016/j.yjmcc.2010.12.009

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  61. P115rgs, A G12/13 Inhibitor, Prevents Vascular Smooth Muscle Cell Activation and Neointima Formation in Response to Balloon Angioplasty

    Akira Takaguri, Katsuhiro Okuda, Katherine Elliott, Keita Kimura, Akinari Hinoki, Kunie Eguchi, Satoru Eguchi

    HYPERTENSION   Vol. 56 ( 5 ) page: E146 - E146   2010.11

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  62. Identification of a Repressor Protein, Mnt, as a Negative Regulator of Pathological Vascular Remodeling

    Akira Takaguri, Katsuhiro Okuda, Kathy Elliott, Akinari Hinoki, Kunie Eguchi, Satoru Eguchi

    HYPERTENSION   Vol. 56 ( 5 ) page: E118 - E118   2010.11

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  63. Caveolin-1 negatively regulates a metalloprotease-dependent EGF receptor transactivation by angiotensin II

    Akira Takaguri, Heigoro Shirai, Akinari Hinoki, Victor Rizzo, Satoru Eguchi

    FASEB JOURNAL   Vol. 24   2010.4

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  64. Pathological neovascularization is reduced by inactivation of ADAM17 in endothelial cells but not in pericytes. Reviewed International journal

    Gisela Weskamp, Karen Mendelson, Steve Swendeman, Sylvain Le Gall, Yan Ma, Stephen Lyman, Akinari Hinoki, Satoru Eguchi, Victor Guaiquil, Keisuke Horiuchi, Carl P Blobel

    Circulation research   Vol. 106 ( 5 ) page: 932 - 40   2010.3

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    RATIONALE: Pathological neovascularization is a critical component of diseases such as proliferative retinopathies, cancer and rheumatoid arthritis, yet much remains to be learned about the underlying causes. Previous studies showed that vascular endothelial growth factor (VEGF)-A activates the membrane-anchored metalloproteinase ADAM17 (a disintegrin and metalloproteinase 17) in endothelial cells, thereby stimulating crosstalk between VEGF receptor 2 and extracellular signal-regulated kinase. These findings raised interesting questions about the role of ADAM17 in angiogenesis and neovascularization in vivo. OBJECTIVE: The objective of this study was to inactivate ADAM17 in endothelial cells or in pericytes to determine how this affects developmental angiogenesis, pathological retinal neovascularization and heterotopic tumor growth. METHODS AND RESULTS: We generated animals in which floxed ADAM17 was removed by Tie2-Cre in endothelial cells, or by smooth muscle (sm) Cre in smooth muscle cells and pericytes. There were no evident developmental defects in either conditional knockout strain, but pathological retinal neovascularization and growth of heterotopically injected tumor cells was reduced in Adam17flox/flox/Tie2-Cre mice, although not in Adam17flox/flox/sm-Cre mice. Moreover, lack of ADAM17 in endothelial cells decreased ex vivo chord formation, and this could be largely restored by addition of the ADAM17 substrate HB-EGF (heparin-binding epidermal growth factor-like growth factor). Finally we found that ADAM17 is important for the VEGF receptor 2 stimulated processing of several receptors with known functions in endothelial cell biology. CONCLUSIONS: These results provide the first evidence for a role for ADAM17 in pathological neovascularization in vivo. Because ADAM17 does not appear to be required for normal developmental angiogenesis or vascular homeostasis, it could emerge as a good target for treatment of pathological neovascularization.

    DOI: 10.1161/CIRCRESAHA.109.207415

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  65. p21-activated kinase 1 participates in vascular remodeling in vitro and in vivo. Reviewed International journal

    Akinari Hinoki, Keita Kimura, Sadaharu Higuchi, Kunie Eguchi, Akira Takaguri, Kazuhiro Ishimaru, Gerald D Frank, William T Gerthoffer, Laura J Sommerville, Michael V Autieri, Satoru Eguchi

    Hypertension (Dallas, Tex. : 1979)   Vol. 55 ( 1 ) page: 161 - 5   2010.1

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    Vascular smooth muscle cell hypertrophy, proliferation, or migration occurs in hypertension, atherosclerosis, and restenosis after angioplasty, leading to pathophysiological vascular remodeling. Angiotensin II and platelet-derived growth factor are well-known participants of vascular remodeling and activate a myriad of downstream protein kinases, including p21-activated protein kinase (PAK1). PAK1, an effector kinase of small GTPases, phosphorylates several substrates to regulate cytoskeletal reorganization. However, the exact role of PAK1 activation in vascular remodeling remains to be elucidated. Here, we have hypothesized that PAK1 is a critical target of intervention for the prevention of vascular remodeling. Adenoviral expression of dominant-negative PAK1 inhibited angiotensin II-stimulated vascular smooth muscle cell migration. It also inhibited vascular smooth muscle cell proliferation induced by platelet-derived growth factor. PAK1 was activated in neointima of the carotid artery after balloon injury in the rat. Moreover, marked inhibition of the neointima hyperplasia was observed in a dominant-negative PAK1 adenovirus-treated carotid artery after the balloon injury. Taken together, these results suggest that PAK1 is involved in both angiotensin II and platelet-derived growth factor-mediated vascular smooth muscle cell remodeling, and inactivation of PAK1 in vivo could be effective in preventing pathophysiological vascular remodeling.

    DOI: 10.1161/HYPERTENSIONAHA.109.143057

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  66. Identification of HGF as a Novel Vascular ADAM Metalloprotease Substrate by Phage Display

    Sadaharu Higuchi, Keita Kimura, Akira Takaguri, Akinari Hinoki, Kunie Eguchi, Gerald D. Frank, Satoru Eguchi

    CIRCULATION   Vol. 120 ( 18 ) page: S1141 - S1141   2009.11

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  67. Signal Cross-Talk Between PDGF Receptor beta and G12/13 Mediates Vascular Smooth Muscle Cell Migration by PDGF-BB: Implication in Neointima Formation

    Akinari Hinoki, Keita Kimura, Kunie Eguchi, Sadaharu Higuchi, Kazuhiro Ishimaru, Michael V. Autieri, Laura J. Sommerville, Gerald D. Frank, Satoru Eguchi

    ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY   Vol. 29 ( 7 ) page: E56 - E57   2009.7

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  68. Role of PAK1 Activation in Migration of VSMC in Vitro and in Arterial Neointima Formation in Vivo

    Keita Kimura, Akinari Hinoki, Kazuhiro Ishimaru, Sadaharu Higuchi, Kunie Eguchi, Michael V. Autieri, Laura J. Sommerville, Gerald D. Frank, Satoru Eguchi

    ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY   Vol. 29 ( 7 ) page: E57 - E57   2009.7

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  69. Endothelial nitric oxide synthase inhibits G12/13 and rho-kinase activated by the angiotensin II type-1 receptor: implication in vascular migration. Reviewed International journal

    Hiroyuki Suzuki, Keita Kimura, Heigoro Shirai, Kunie Eguchi, Sadaharu Higuchi, Akinari Hinoki, Kazuhiro Ishimaru, Eugen Brailoiu, Danny N Dhanasekaran, Laura N Stemmle, Timothy A Fields, Gerald D Frank, Michael V Autieri, Satoru Eguchi

    Arteriosclerosis, thrombosis, and vascular biology   Vol. 29 ( 2 ) page: 217 - 24   2009.2

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    BACKGROUND: Although, endothelial nitric oxide (NO) synthase (eNOS) is believed to antagonize vascular remodeling induced by the angiotensin II (AngII) type-1 receptor, the exact signaling mechanism remains unclear. METHODS AND RESULTS: By expressing eNOS to vascular smooth muscle cells (VSMCs) via adenovirus, we investigated a signal transduction mechanism of the eNOS gene transfer in preventing vascular remodeling induced by AngII. We found marked inhibition of AngII-induced Rho/Rho-kinase activation and subsequent VSMC migration by eNOS gene transfer whereas G(q)-dependent transactivation of the epidermal growth factor receptor by AngII remains intact. This could be explained by the specific inhibition of G(12/13) activation by eNOS-mediated G(12/13) phosphorylation. CONCLUSIONS: The eNOS/NO cascade specifically targets the Rho/Rho-kinase system via inhibition of G(12/13) to prevent vascular migration induced by AngII, representing a novel signal cross-talk in cardiovascular protection by NO.

    DOI: 10.1161/ATVBAHA.108.181024

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  70. Distinct roles of protease-activated receptors in signal transduction regulation of endothelial nitric oxide synthase. Reviewed International journal

    Hiroyuki Suzuki, Evangeline D Motley, Kunie Eguchi, Akinari Hinoki, Heigoro Shirai, Vabren Watts, Laura N Stemmle, Timothy A Fields, Satoru Eguchi

    Hypertension (Dallas, Tex. : 1979)   Vol. 53 ( 2 ) page: 182 - 8   2009.2

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    Protease-activated receptors (PARs), such as PAR1 and PAR2, have been implicated in the regulation of endothelial NO production. We hypothesized that PAR1 and PAR2 distinctly regulate the activity of endothelial NO synthase through the selective phosphorylation of a positive regulatory site, Ser(1179), and a negative regulatory site, Thr(497), in bovine aortic endothelial cells. A selective PAR1 ligand, TFLLR, stimulated the phosphorylation of endothelial NO synthase at Thr(497). It had a minimal effect on Ser(1179) phosphorylation. In contrast, a selective PAR2 ligand, SLIGRL, stimulated the phosphorylation of Ser(1179) with no noticeable effect on Thr(497). Thrombin has been shown to transactivate PAR2 through PAR1. Thus, thrombin, as well as a peptide mimicking the PAR1 tethered ligand, TRAP, stimulated phosphorylation of both sites. Also, thrombin and SLIGRL, but not TFLLR, stimulated cGMP production. A G(q) inhibitor blocked thrombin- and SLIGRL-induced Ser(1179) phosphorylation, whereas it enhanced thrombin-induced Thr(497) phosphorylation. In contrast, a G(12/13) inhibitor blocked thrombin- and TFLLR-induced Thr(497) phosphorylation, whereas it enhanced the Ser(1179) phosphorylation. Although a Rho-kinase inhibitor, Y27632, blocked the Thr(497) phosphorylation, other inhibitors that targeted Rho-kinase failed to block TFLLR-induced Thr(497) phosphorylation. These data suggest that PAR1 and PAR2 distinctly regulate endothelial NO synthase phosphorylation and activity through G(12/13) and G(q), respectively, delineating the novel signaling pathways by which the proteases act on protease-activated receptors to potentially modulate endothelial functions.

    DOI: 10.1161/HYPERTENSIONAHA.108.125229

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  71. Involvement of Adam17 in Neointima Formation after Vascular Injury; Potential Role of Tyrosine Phosphorylation on its Activity

    Akinari Hinoki, Sadaharu Higuchi, Keita Kimura, Kunie Eguchi, Michael V. Autieri, Laura J. Sommerville, Gerald D. Frank, Satoru Eguchi

    CIRCULATION   Vol. 118 ( 18 ) page: S372 - S372   2008.10

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  72. Caveolin-1 regulates ADAM17-dependent EGF receptor transactivation induced by angiotensin II

    Akinari Hinoki, Keita Kimura, Sadaharu Higuchi, Kunie Eguchi, Baohua Yang, Victor Rizzo, Gerald D. Frank, Satoru Eguchi

    HYPERTENSION   Vol. 52 ( 4 ) page: E57 - E57   2008.10

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  73. ADAM17 is a new therapeutic target for neointima formation after vascular injury: Impact of tyrosine phosphorylation on its activity

    Keita Kimura, Akinari Hinoki, Sadaharu Higuchi, Heigoro Shirai, Kunie Eguchi, Michael V. Autieri, Laura J. Sommerville, Gerald D. Frank, Satoru Eguchi

    HYPERTENSION   Vol. 52 ( 4 ) page: E76 - E76   2008.10

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  74. Central role of Gq in the hypertrophic signal transduction of angiotensin II in vascular smooth muscle cells. Reviewed International journal

    Haruhiko Ohtsu, Sadaharu Higuchi, Heigoro Shirai, Kunie Eguchi, Hiroyuki Suzuki, Akinari Hinoki, Eugen Brailoiu, Andrea D Eckhart, Gerald D Frank, Satoru Eguchi

    Endocrinology   Vol. 149 ( 7 ) page: 3569 - 75   2008.7

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    The angiotensin II (AngII) type 1 receptor (AT(1)) plays a critical role in hypertrophy of vascular smooth muscle cells (VSMCs). Although it is well known that G(q) is the major G protein activated by the AT(1) receptor, the requirement of G(q) for AngII-induced VSMC hypertrophy remains unclear. By using cultured VSMCs, this study examined the requirement of G(q) for the epidermal growth factor receptor (EGFR) pathway, the Rho-kinase (ROCK) pathway, and subsequent hypertrophy. AngII-induced intracellular Ca(2+) elevation was completely inhibited by a pharmacological G(q) inhibitor as well as by adenovirus encoding a G(q) inhibitory minigene. AngII (100nm)-induced EGFR transactivation was almost completely inhibited by these inhibitors, whereas these inhibitors only partially inhibited AngII (100nm)-induced phosphorylation of a ROCK substrate, myosin phosphatase target subunit-1. Stimulation of VSMCs with AngII resulted in an increase of cellular protein and cell volume but not in cell number. The G(q) inhibitors completely blocked these hypertrophic responses, whereas a G protein-independent AT(1) agonist did not stimulate these hypertrophic responses. In conclusion, G(q) appears to play a major role in the EGFR pathway, leading to vascular hypertrophy induced by AngII. Vascular G(q) seems to be a critical target of intervention against cardiovascular diseases associated with the enhanced renin-angiotensin system.

    DOI: 10.1210/en.2007-1694

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  75. Involvement of caveolin-1 in a metalloprotease-dependent EGF receptor transactivation and subsequent cell hypertrophy induced by angiotensin II

    Sadaharu Higuchi, Akinari Hinoki, Heigoro Shirai, Kunie Eguchi, Gerald D. Frank, MaryEllen Carlile, Baohua Yang, Victor Rizzo, Satoru Eguchi

    ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY   Vol. 28 ( 6 ) page: E45 - E45   2008.6

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  76. ADAM17 mediates neointima formation: Potential requirement of its tyrosine phosphorylation

    Akinari Hinoki, Sadaharu Higuchi, Heigoro Shirai, Kunie Eguchi, Gerald D. Frank, Satoru Eguchi

    ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY   Vol. 28 ( 6 ) page: E45 - E45   2008.6

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  77. Novel role of protein kinase C-delta Tyr 311 phosphorylation in vascular smooth muscle cell hypertrophy by angiotensin II. Reviewed International journal

    Hidekatsu Nakashima, Gerald D Frank, Heigoro Shirai, Akinari Hinoki, Sadaharu Higuchi, Haruhiko Ohtsu, Kunie Eguchi, Archana Sanjay, Mary E Reyland, Peter J Dempsey, Tadashi Inagami, Satoru Eguchi

    Hypertension (Dallas, Tex. : 1979)   Vol. 51 ( 2 ) page: 232 - 8   2008.2

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    We have shown previously that activation of protein kinase C-delta (PKC delta) is required for angiotensin II (Ang II)-induced migration of vascular smooth muscle cells (VSMCs). Here, we have hypothesized that PKC delta phosphorylation at Tyr(311) plays a critical role in VSMC hypertrophy induced by Ang II. Immunoblotting was used to monitor PKC delta phosphorylation at Tyr(311), and cell size and protein measurements were used to detect hypertrophy in VSMCs. PKC delta was rapidly (0.5 to 10.0 minutes) phosphorylated at Tyr(311) by Ang II. This phosphorylation was markedly blocked by an Src family kinase inhibitor and dominant-negative Src but not by an epidermal growth factor receptor kinase inhibitor. Ang II-induced Akt phosphorylation and hypertrophic responses were significantly enhanced in VSMCs expressing PKC delta wild-type compared with VSMCs expressing control vector, whereas the enhancements were markedly diminished in VSMCs expressing a PKC delta Y311F mutant. Also, these responses were significantly inhibited in VSMCs expressing kinase-inactive PKC delta K376A compared with VSMCs expressing control vector. From these data, we conclude that not only PKC delta kinase activation but also the Src-dependent Tyr(311) phosphorylation contributes to Akt activation and subsequent VSMC hypertrophy induced by Ang II, thus signifying a novel molecular mechanism for enhancement of cardiovascular diseases induced by Ang II.

    DOI: 10.1161/HYPERTENSIONAHA.107.101253

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  78. Rho-kinase mediates activation of PAK1 and its interaction with mnt by angiotensin II in vascular smooth muscle cells: Novel combination analysis using a phage display and LC/MS analysis

    Heigoro Shirai, Sadaharu Higuchi, Akinari Hinoki, Gerald D. Frank, Evangeline D. Motley, Tomoyuki Oe, Satoru Eguchi

    HYPERTENSION   Vol. 50 ( 4 ) page: E96 - E96   2007.10

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  79. Novel involvement of caveolin-1 in adam 17-dependent EGF receptor transactivation induced by angiotensin II

    Heigoro Shirai, Sadaharu Higuchi, Akinari Hinoki, Kunie Eguchi, Gerald D. Frank, MaryEllen Carlile-Klusacek, Baohua Yang, Victor Rizzo, Satoru Eguchi

    CIRCULATION   Vol. 116 ( 16 ) page: 236 - 236   2007.10

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  80. Distinct molecular regulation and eNOS sensitivity of Rho/ROCK activation and EGFR transactivation through the angiotensin II type 1 receptor

    Akinari Hinoki, Heigoro Shirai, Sadaharu Higuchi, Kunie Eguchi, Gerald D. Frank, Gerald D. Frank

    HYPERTENSION   Vol. 50 ( 4 ) page: E97 - E97   2007.10

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  81. Suppression of proinflammatory cytokine production in macrophages by lansoprazole.

    Hinoki A, Yoshimura K, Fujita K, Akita M, Ikeda R, Nagashima M, Nomura M, Satomi A

    Pediatric surgery international   Vol. 22 ( 11 ) page: 915 - 23   2006.11

  82. Suppression of proinflammatory cytokine production in macrophages by lansoprazole. Reviewed International journal

    Akinari Hinoki, Kazunori Yoshimura, Keiko Fujita, Masumi Akita, Rie Ikeda, Masabumi Nagashima, Masahiko Nomura, Akira Satomi

    Pediatric surgery international   Vol. 22 ( 11 ) page: 915 - 23   2006.11

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    Macrophages (MPs) produce increased levels of proinflammatory cytokines in Crohn's disease; these cytokines are thought to play a central role in the occurrence of the disease. Biologics are currently available for anti-cytokine therapy, but treating intestinal inflammation through direct suppression of proinflammatory cytokine production could be more effective. P-ATPase inhibitors have been reported to be anti-inflammatory, and these inhibitors might suppress the production of MP proinflammatory cytokines. In this study, we examined the effect of two types of ATPase inhibitors on the expression patterns of typical proinflammatory cytokines. Peritoneal MPs from 6- to 8-week-old mice were cultured for 48 h in the presence of lansoprazole (P-ATPase inhibitor), bafilomycin A(1) (V-ATPase inhibitor), or the control solvent dimethylsulfoxide. The MPs were then examined for cytokine expression by quantitative real-time polymerase chain reaction (PCR), and culture supernatants were examined for cytokine production with a multiplex assay in a suspension array system. The possible existence of P-ATPase mRNA in MPs was explored using reverse-transcriptase PCR. P-ATPase mRNA was not detected in MP cells. However, all examined proinflammatory cytokines decreased significantly in their mRNA and protein expression in the lansoprazole-treated group. Conversely, bafilomycin A(1) increased the levels of these cytokines. Lansoprazole might be useful for the treatment of inflammatory bowel diseases (IBDs), including Crohn's disease, as it suppresses the production of relevant MP proinflammatory cytokines. However, because P-ATPase was not detected in MPs, the mechanism is unclear and remains to be studied further in an IBD animal model.

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KAKENHI (Grants-in-Aid for Scientific Research) 18

  1. Possible treatment strategy of one-carbon metabolism on pancreatic cancer management

    Grant number:21K07147  2021.4 - 2024.3

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    Authorship:Coinvestigator(s) 

  2. 腎芽腫患児の代謝物網羅解析によるバイオマーカーの探索と創薬への挑戦

    Grant number:21K07805  2021.4 - 2024.3

    田中 裕次郎, 大澤 毅, 内田 広夫, 檜 顕成, 大島 一夫, 城田 千代栄, 田井中 貴久, 住田 亙, 横田 一樹

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    腎芽腫は小児腎腫瘍の90%を占めるが、全体の約10%に予後不良群を認め、診断バイオマーカーが存在しない。最近メタボロミクス技術の発展により生体内の代謝情報を鋭敏且つ包括的に捉えることが可能となり、様々な癌種において新たなバイオマーカーや病態の解明が進んでいる。腎芽腫においても代謝変動の解明が病因解明や新規治療法の開発に寄与すると考えられるが、その代謝変動に着目した診断マーカーや創薬は前例がない。本研究では腎芽腫をターゲットに尿だけでなく、血液、がん組織を加えた腎芽腫50サンプルの代謝物変動を捉えるメタボローム解析を行い、疾患特異的なバイオマーカー探索とその病態解明に挑む。

  3. Development of fluorescent probes for diagnosis and treatment of pediatric surgical diseases

    Grant number:21K08640  2021.4 - 2024.3

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  4. The establish of off the job training for pediatric minimally invasive surgery and automated analysis system of operative technique

    Grant number:19H04225  2019.4 - 2022.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)  Grant-in-Aid for Scientific Research (B)

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    Authorship:Coinvestigator(s) 

  5. Development of a self-supporting ultrathin polymer film (nanosheet) for preventing postoperative suture failure and adhesion

    Grant number:20K08979  2020.4 - 2023.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

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    Authorship:Coinvestigator(s) 

  6. Development of tracheal stents made from new biodegradable Magnesium alloy

    Grant number:19K22654  2019.6 - 2021.3

    Grant-in-Aid for Challenging Research (Exploratory)

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    Authorship:Coinvestigator(s) 

  7. Single cell transcriptome analysis for the intestinal immunity of neonates

    Grant number:18K19503  2018.6 - 2020.3

    Grant-in-Aid for Challenging Research (Exploratory)

    SAWA SHINICHIRO

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    Authorship:Coinvestigator(s) 

    The first aim of this project was to understand composition and function of immune cells in human neonatal gut. We succeeded in setting up single cell transcriptome analysis about human intestinal cells. The second aim was to clarify etiology of neonatal necrotizing colitis (NEC). In NEC patients, intestinal inflammation and tissue necrosis is evident. Using single cell transcriptome analysis, we identified enhanced expression of chemokine receptors and adhesion molecules on T cells in NEC patients.

  8. リンパ管腫のリンパ動態に基づいた光線力学療法による根治の試み

    Grant number:18K08559  2018.4 - 2021.3

    高橋 正貴

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    Authorship:Coinvestigator(s) 

    本研究では、病変特異的な異常リンパ動態を利用して、病変にのみICGを取り込ませ、蛍光イメージングによる局在診断の有用性を検証する。さらに同部位に近赤外光を照射した際に発生する温熱を利用して、リンパ管腫を選択的に治療する光温熱治療の有効性を実証する。
    申請者らはすでに、In vitro実験の検証により、リンパ管腫リンパ管内皮細胞(以下HL-LEC)はICGを取り込み、取り込んだ細胞に近赤外光を照射すると、100%近い細胞の細胞死を誘導することも確認している。また、設定温度が47度以上で確実に細胞死を誘導することを確認している。
    今回、申請者は既に確立した背部皮下リンパ管腫モデルマウスを用いてICGによる蛍光イメージングならびに光温熱治療の治療効果を確認した。背部皮下のリンパ管腫モデルマウスにICGを嚢胞内に打ち込み、近赤外光を照射したところ、病理組織学的に移植片のリンパ管内皮細胞を細胞死に導くことができることを確認した。
    申請書類と同等の進捗状況である。
    申請者らが樹立したリンパ管腫内皮細胞に発光遺伝子(Nano-Lantern)を導入した細胞系を確立している。それを用いて治療効果の検証には、生体イメージングシステム(IVIS&#174;)で、病変の増殖・縮退を経時的に繰り返し観察する。この細胞を用いて作製したモデルマウスにおいては、体外から無侵襲(体毛の剃毛すら不要)かつ短時間(~1 s)に腫瘍局在、サイズ等を検出することができる。一方で超音波イメージングでは50 μmの分解能で、嚢胞や周辺組織を描出できる。定量的な治療効果の検証ができると期待していたが、Nano-Lantern入りHL-LECはIVISで発光せず、定量的な比較が困難であることが判明した。また、モデルマウスの作成に3-4か月を要する。
    現時点では当初の予定通りに進んでいるが、上記事項を考慮して研究を進めていく。
    動物モデルで治療効果の有効性が明らかなので、対照群と比較して量的に有効性を示す必要性がある。
    移植細胞の特殊性と上述した事項から、現時点では定量的評価が困難である。定量的評価を確立させる必要が有るために、HL-LECにfflucやAka-Lucの導入し、In vivo imaging systemを用いて経時的に半定量的評価を行うモデルマウスの作成を予定している。
    それらの体表モデルを用いて体表からの照射を行い、コントロール群との治療効果の比較、照射部位の副作用の比較検討を定量的行う。
    次のステップとして臨床で遭遇する深部体腔内のリンパ管腫病変を想定し、筋肉内病変モデルや後腹膜腫瘍モデルなどのマウスを作製して、本診断・治療法の有効性を確認する。実臨床に即した照射方法として体表照射のみならず、手術時併用を想定に開創時の照射などを検討予定である。

  9. Challenge to Optimize allocation of Pediatric Surgical Resources by using Remote Medical Platform

    Grant number:17H06280  2017.6 - 2020.3

    Grant-in-Aid for Challenging Research (Pioneering)

    Shirota Chiyoe

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    Authorship:Coinvestigator(s) 

    By developing an application and using one-to-many mobile telemedicine to securely link medical sites, we aimed to solve pediatric surgery medical infrastructure and at the same time spread and develop highly specialized telemedicine support. Many doctors can use the application to create a situation where dispersed cases in each region are aggregated in one place (one-to-many remote video conference, image sharing is possible on a smartphone). Can be shared in real time, participate in the consideration of treatment policy, and exchange opinions. We have started to provide highly specialized telemedicine support, which is available 24 hours a day, by securely linking medical fields with desired doctors and hospitals in Japan. The effective use of the system has made it possible to virtually consolidate a specialist with valuable cases.

  10. Establishment of an analytical workflow to elucidate the molecular biology of the pathogenesis of gastrointestinal diseases in neonates

    Grant number:17H04235  2017.4 - 2020.3

    Tanaka Yujiro

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    Authorship:Coinvestigator(s) 

    Lymphocytes of 71 resected human bowels were examined using flow cytometry. Type 3 innate lymphoid cells (ILC3), which is known to regulate bowel immunity, was detected in all specimens. However, the percentage of ILC3 was not constant according to the condition of patients, e.g. gestational week and disease. Studying the bowel specimens of emergency laparotomy in human neonates, we also investigated the differences in gene expression between necrotizing enteritis and non-necrotic intestinal perforation. We studied the gene expression on a cell-by-cell basis of about 10,000 cells per each case, so we can assess what cells were specifically showing abnormal responses. To date, there have been no reports of gene expression analysis on a cell-by-cell basis. In necrotizing enteritis, T cells were dominant and pathways concerning inflammation, e.g. MYC targets, mTORC1 signaling, TNFA signaling were activated. In non-necrotic intestinal perforation, innate monocytic cells were the major.

  11. Highly efficient cancer treatment system combined with a drug-delivery photoabsorbent agent and a tempreature-controled laser system

    Grant number:17H02114  2017.4 - 2020.3

    Morimoto Yuji

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    Authorship:Coinvestigator(s) 

    The applicants have been developing a novel cancer treatment system combined with a drug delivery system light-absorbing agent (ICG lactosome) and photothermal therapy using near-infrared light irradiation system.
    In this project, we have developed a laparoscopic camera with an ultra-compact thermosensor array and established a temperature-controlled, endoscopic laser ablation system.

  12. a new wearable multi-lead electrocardiogram measuring system for super-ageing society

    Grant number:16K12957  2016.4 - 2019.3

    UCHIDA HIROO

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    Authorship:Coinvestigator(s) 

    To develop a wearable multi-lead electrocardiogram (ECG) measuring system, we fabricated the electrode and wiring by using electrostatic flocking technology on a textile. By using this technology, it was possible to fabricate many electrodes and wiring, simultaneously. The fabricated wiring and electrodes had stretchability and wash resistance properties. To use dry electrodes, it is important to reduce the influence of motion artifacts (MAs). we conducted experiments with a human body to determine the relationship between the contact pressure and the MAs. under the pressures of 1000 Pa , 2000Pa and 4000Pa, the ECG signals under rest and deep breathing conditions were able to be measured without MAs. Finally, we fabricated the wearable ECG measuring system and succeeded in measuring 18-lead ECG signals. The measured ECG waveform is in good agreement with the ECG waveform measured by a commercial system.

  13. Development of a new biodegradable magnesium alloy for medical equipment

    Grant number:16H03197  2016.4 - 2019.3

    UCHIDA HIROO

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    Authorship:Coinvestigator(s) 

    We focus on Mg alloy because it is biodegradable, and has excellent biocompatibility. Mg-based medical devices have already been clinically used as vascular stents and orthopaedic screws. However, Mg staples can easily fracture or degrade at the corners of the B-shape after stapling because of their vulnerability to stress corrosion. Another concern is the production of hydrogen gas caused by the rapid corrosion of Mg in physiological environments.
    To address the above challenges, we first redesigned the optimal staple shape to a more rounded form without acute bending points to reduce stress concentrations introduced by stapling and anastomosing. We also developed a novel Mg alloy with sufficiently high ductility to be finely processed to form the shape of a staple and stapled without fracturing. These two patents made us successful in developing Mg alloy staples, and we have confirmed them to be suitable for surgical stapling by rabbit intestinal anastomosis.

  14. Development of a next generation photothermal therapy using a light-absorbing drug that selectively accumulates in lesions for pediatric cancer

    Grant number:16K15741  2016.4 - 2018.3

    TAINAKA Takahisa

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    Authorship:Coinvestigator(s) 

    Even accompanied with infiltration / metastasis, pediatric solid cancer can be curable if the tumor can be completely removed by multidisciplinary treatment, but it is not easy in actual clinical practice. However, applicants have developed a new DDS (Drug Delivery System) type drug "ICG lactosome", which made it possible to carry out diagnosis and therapy simultaneously (Theranostics).ICG lactosome was proved to selectively accumulate in tumor. By fluorescence diagnosis and photothermal treatment using ICG lactosome, we succeeded in shrinking tumors of infiltrated neuroblastoma model mice.Photothermally treated tumor-bearing mice of which the tumor temperature was maintained at 43°C or more during the treatment showed almost completely tumor-extinction.

  15. Development of Retained Surgical Gauze Detection System before Closing Surgical Incisions.

    Grant number:15K15258  2015.4 - 2018.3

    Hinoki Akinari

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    Authorship:Principal investigator 

    Grant amount:\3510000 ( Direct Cost: \2700000 、 Indirect Cost:\810000 )

    We found retained surgical gauze while creating several types of surgical gauze detection devices and surgical gauze for detection and detecting eddy current of metallic fiber included in the surgical gauze for detection. Actually, metallic fiber were included in surgical gauze and the change of eddy current was detected from the outside of the body before closing incisions, and the presence or absence of remnant gauze was verified. With respect to silver, the search for degradation kinetics in Both quantitative results of metallic element (silver) and pH change of the extract were very small, and it was judged that the influence of silver itself on the human body was extremely small. Considering biocompatibility, metallic resistance, actual detection distance, and decomposition dynamics in simulated environment of silver in the body, at present, it is necessary to set 4 or 16 circular sections (closed loop windings 3 to 7 times) of silver fibers.

  16. THE DEVELOPMENT OF LAPAROSCOPIC SURGERY USING THE PERINEAL APPROACH THROUGH THE PRESACRAL SPACE

    Grant number:25670562  2013.4 - 2017.3

    TANIMIZU TAKEMARU

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    Authorship:Coinvestigator(s) 

    Paying attention anatomically to the fact that there are no major blood vessels or nerve plexus in the presacral space median, the possibility of laparoscopic surgery using the presacral route was examined. To confirm the feasibility, difficulty and safety of the surgical technique LSPAPS(Laparoscopic Surgery using the Perineal Approach through the Presacral Space) four examinations were carried out: 1. Animal Experiment,
    2. Verification by Imaging, 3. Confirmation of Normal Anatomy on Cadavers 4. Histological Examination.

  17. Management against surgical stress in compromised hosts

    Grant number:25293369  2013.4 - 2016.3

    Kinoshita Manabu

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    Authorship:Coinvestigator(s) 

    Compromised hosts enhanced productions of ROS and proinflammatory cytokines against surgical stress. Regulation of such inflammatory responses improves organ damage but these responses are beneficial for bacterial elimination and liver regeneration. Resident Kupffer cells (KC) are important for bacterial elimination while bone marrow-derived recruiting KC are involved in TNF-FasL-mediated hepatic injuries. Compromised hosts showed decreased resident KC but increased recruiting KC, leading to exacerbation of infection and organ injury. Restoration of KC phenotypic alteration and their functions are crucial for management against surgical stress. We also investigated the efficacy of nanosheet for sealing and stopping massive hemorrhage and developed the antimicrobial silver-loaded nanosheet. We examined the efficacy of hemostatic nanoparticles against massive hemorrhage with coagulopathy and also investigated the immunostimulative effect of photodynamic therapy in mouse MRSA arthritis.

  18. Development of Gauze Detection System before Closing a Surgical Incision Using Disturbance of Magnetic Field by Magnetized Body

    Grant number:24659254  2012.4 - 2016.3

    Hinoki Akinari

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    Authorship:Principal investigator 

    Grant amount:\1690000 ( Direct Cost: \1300000 、 Indirect Cost:\390000 )

    We tried to structure the gauze detection system before closing a surgical incision, which can detect remnant gauze outside the body in a short time even if it remains inside the body during surgery. We found remnant gauze while creating several types of gauze detection devices and gauze for detection and detecting a metallic fiber included in the gauze for detection. By the past improvement of the gauze detection system before closing a surgical incision, gauze for detection can be now detected about 30cm away from it even though the detection distance was about 10cm when we initially started this study. We cannot specify the position of the remnant gauze by image still now however we created a prototype of gauze detection device, which appeals to visual and auditory senses at the same time.

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Industrial property rights 5

  1. 新規検査開発サーバ及び新規検査開発方法

    東海国立大学機構,日立製作所

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    Date applied:2020.2

    Announcement no:2021-128115  Date announced:2021.9

    Country of applicant:Domestic   Country of acquisition:Domestic

  2. 尿中腫瘍マーカーによるがん検出方法、キット及び装置

    東海国立大学機構,日立製作所

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    Date applied:2018.11

    Announcement no:2020-079729  Date announced:2020.5

    Country of applicant:Domestic   Country of acquisition:Domestic

  3. 医療用線状材料

    法人名大,三井金属鉱業

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    Date applied:2018.6

    Announcement no:WO 2018/230415  Date announced:2018.12

    Country of applicant:Foreign country   Country of acquisition:Foreign country

  4. 小児がん検査用尿中代謝物マーカー

    東海国立大学機構,日立製作所

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    Date applied:2018.3

    Announcement no:2019-168319  Date announced:2019.10

    Country of applicant:Domestic   Country of acquisition:Domestic

  5. 生体吸収性ステープル

    法人名大,産業技術総合研究所

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    Date applied:2016.10

    Announcement no:WO 2017/061616  Date announced:2017.4

    Country of applicant:Foreign country   Country of acquisition:Foreign country

 

Teaching Experience (On-campus) 1

  1. Pediatric Surgery

    2021

Teaching Experience (Off-campus) 1

  1. 小児外科

    2020.4 National Defense Medical College)

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    Level:Undergraduate (specialized)