Language：Japanese   Publisher：Scientific Reports  

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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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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Language：Japanese   Publishing type：Research paper (scientific journal)  

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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Language：Japanese   Publishing type：Research paper (scientific journal)  

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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Language：Japanese   Publishing type：Research paper (scientific journal)  

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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DOI： 10.1007/s00383-021-04873-7

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Language：Japanese   Publishing type：Research paper (scientific journal)  

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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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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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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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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Language：Japanese   Publishing type：Research paper (scientific journal)  

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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Publisher：The Japanese Society of Pediatric Surgeons  

<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

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

DOI： 10.1117/12.2581261

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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.

DOI： 10.1186/s12893-020-00986-3

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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.

DOI： 10.1007/s00464-019-07108-y

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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.

DOI： 10.1186/s12887-020-02183-w

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Publisher：日本膵・胆管合流異常研究会  

DOI： 10.34410/jspbm.43.0_84

Publisher：日本膵・胆管合流異常研究会  

DOI： 10.34410/jspbm.43.0_36

Language：Japanese   Publishing type：Research paper (scientific journal)  

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.

DOI： 10.1038/s41598-019-51123-x

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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.

DOI： 10.1038/s41598-019-42027-x

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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.

DOI： 10.1080/08941939.2017.1366603

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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.

DOI： 10.1002/jhbp.594

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

© 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.

DOI： 10.1007/978-3-030-32689-0_11

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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.

DOI： 10.1007/s00383-018-4320-7

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Language：Japanese   Publishing type：Research paper (scientific journal)  

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.

DOI： 10.1016/j.jpedsurg.2018.04.030

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Language：Japanese   Publishing type：Research paper (scientific journal)  

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.

DOI： 10.1007/s00383-018-4318-1

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Language：Japanese   Publishing type：Research paper (scientific journal)  

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.

DOI： 10.1007/s00383-018-4313-6

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Language：Japanese   Publishing type：Research paper (scientific journal)  

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.

DOI： 10.1007/s00383-018-4323-4

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Language：Japanese   Publishing type：Research paper (scientific journal)  

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.

DOI： 10.1007/s00383-018-4324-3

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Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：Institute of Electrical and Electronics Engineers Inc.  

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.

DOI： 10.23919/ICEP.2018.8374690

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Language：Japanese   Publishing type：Research paper (scientific journal)  

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.

DOI： 10.1016/j.jpedsurg.2018.01.019

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Language：Japanese   Publishing type：Research paper (scientific journal)  

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.

DOI： 10.1089/lap.2017.0307

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Language：Japanese   Publishing type：Research paper (scientific journal)  

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.

DOI： 10.1186/s12887-018-1085-z

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

© 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.

DOI： 10.1007/978-3-030-00934-2_26

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Language：Japanese   Publishing type：Research paper (scientific journal)  

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.

DOI： 10.1016/j.jpedsurg.2017.08.056

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Language：Japanese   Publishing type：Research paper (scientific journal)  

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.

DOI： 10.1186/s12893-017-0313-z

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.12659/AJCR.903465

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PubMed

Language：Japanese   Publishing type：Research paper (scientific journal)  

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.

DOI： 10.1186/s12887-017-0826-8

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Language：Japanese   Publishing type：Research paper (scientific journal)  

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.

DOI： 10.1089/lap.2016.0207

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Language：Japanese   Publishing type：Research paper (scientific journal)  

© 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.

DOI： 10.4103/0972-9941.181771

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Language：Japanese   Publishing type：Research paper (scientific journal)  

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.

DOI： 10.1002/jhbp.395

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Language：Japanese   Publishing type：Research paper (scientific journal)  

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.

DOI： 10.18999/nagjms.78.4.447

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Language：Japanese   Publishing type：Research paper (scientific journal)  

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.

DOI： 10.1007/s00383-016-3939-5

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Language：English   Publishing type：Research paper (scientific journal)  

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.

DOI： 10.1002/bjs.10122

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OPTICAL SOC JAPAN  

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.

DOI： 10.1007/s10043-015-0171-9

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Lippincott Williams and Wilkins  

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.

DOI： 10.1097/01.XPS.0000473472.66487.e6

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Lippincott Williams and Wilkins  

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.

DOI： 10.1097/01.XPS.0000476011.68016.bc

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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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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

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Publishing type：Research paper (scientific journal)  

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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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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Publishing type：Research paper (scientific journal)  

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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Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

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Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

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Language：English   Publisher：FEDERATION AMER SOC EXP BIOL  

Web of Science

Publishing type：Research paper (scientific journal)  

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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PubMed

Publishing type：Research paper (scientific journal)  

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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PubMed

Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Web of Science

Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Web of Science

Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Web of Science

Publishing type：Research paper (scientific journal)  

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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PubMed

Publishing type：Research paper (scientific journal)  

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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PubMed

Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Web of Science

Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Web of Science

Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Web of Science

Publishing type：Research paper (scientific journal)  

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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PubMed

Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Web of Science

Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Web of Science

Publishing type：Research paper (scientific journal)  

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

Scopus

PubMed

Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Web of Science

Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Web of Science

Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Web of Science

DOI： 10.1007/s00383-006-1767-8

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

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.

PubMed