Keigo Nara

Osaka City University, Ōsaka, Ōsaka, Japan

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Publications (20)32.41 Total impact

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    ABSTRACT: Introduction With the recent improvements in the prognosis of pediatric malignancies, the number of patients surviving long-term after surgery has been increasing. Therefore, the late effects of cancer treatments are important issues. In this study, we analyzed the problems associated with the treatment of pediatric patients during the long-term follow-up after surgery. Patients and Methods A total of 64 patients with pediatric malignancies who underwent surgical treatment and were followed up for more than 5 years and who were older than 13 years of age were included in this study. The average age was 20.8 (13-33) years, and the follow-up ranged from 5 to 31 years (mean, 17.7 years). Twenty-one patients (32.3%) received high-dose chemotherapy (HDC) and nine (14.1%) received radiotherapy. Results In this study, 46 patients (71.9%) developed at least one problem during the follow-up period. With regard to the surgical problems, 14 patients underwent nephrectomy, and 1 of them developed renal failure. One patient received cystectomy with urinary tract reconstruction. One patient received a partial vaginectomy. Two cases with ovarian tumors received oophorectomy, one of whom also received partial hysterectomy. Other complications such as ileus, scoliosis, and leg length discrepancies were seen in some patients. In terms of the medical problems, 15 patients showed growth retardation and 2 were treated with growth hormone therapy. Gonadal dysfunction was observed in 23 patients, and 8 of them were treated with hormone replacement therapy. Six patients developed hypothyroidism, two of whom were treated with thyroid hormone replacement therapy. Other medial issues, such as hearing impairment, low bone mineral density, and hepatitis, were seen in some patients. The rate of growth retardation, gonadal dysfunction, and hypothyroidism were significantly higher in the patients who received HDC (p < 0.05). There was one case of second malignancy of the parotid gland. Conclusion Various treatment-related complications may occur even many years after treatment, especially in patients who receive HDC. Medical problems, especially endocrine disorders, appear to be more serious than surgery-related problems. Lifetime medical surveillance and continuous follow-up by not only pediatric surgeons but also by various specialists, such as pediatric oncologists, pediatric endocrinologists, urologists, and gynecologists, are necessary.
    European Journal of Pediatric Surgery 08/2014; · 0.84 Impact Factor
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    ABSTRACT: Introduction An increasing number of children with advanced malignancies have recently received high-dose chemotherapy (HDC) with hematopoietic stem cell transplantation (HSCT), followed by surgery. In this study, we reviewed our experience with surgery after HDC and autologous (auto) or allogeneic (allo) HSCT to elucidate the problems associated with this treatment and establish the optimum surgical management strategy. Patients and Methods We retrospectively reviewed the cases of 24 children with advanced malignancy treated with HDC and HSCT before tumor resection at our institution. The tumors included 18 neuroblastomas, 5 soft tissue sarcomas, 2 hepatoblastomas, and 1 Wilms tumor. The source of hematopoietic stem cells was auto-HSCT in 19 patients and allo-HSCT in 5 patients. To be able to undergo surgery, it was necessary that the patient's general condition, including hemostasis, should be fairly good and that the results of hematological examinations should include a white blood cell (WBC) count of > 1,000/µL, hemoglobin level of > 10 g/dL and platelet count of > 5 × 10(4)/µL. Results The mean duration before WBC recovery after HSCT was 14.5 ± 1.4 days after auto-HSCT and 23.8 ± 1.2 days after allo-HSCT, respectively (p < 0.01). The mean duration before platelet recovery after HSCT was 46.5 ± 5.2 days for auto-HSCT and 48.6 ± 5.5 days for allo-HSCT (not significant [n.s.]). The mean interval between allo-HSCT and surgery was significantly longer (92.8 ± 6.2 days) than that between auto-HSCT and surgery (57.0 ± 3.9 days) (p < 0.01), likely because of the use of steroids and immunosuppressants after HSCT. The tumors were completely resected in all cases without severe complications. All the patients treated with allo-HSCT had an acute graft versus host (aGVH) reaction at 2 to 3 weeks after HSCT, and specifically required the administration of steroids and immunosuppressants to prevent aGVH. The postoperative complications included paralytic ileus in two cases and a tacrolimus-associated encephalopathy in one case involving allo-HSCT. In half of the patients, the WBC count was not elevated after surgery, whereas the postoperative serum C-reactive protein (CRP) level was elevated in all cases. Conclusions Our data indicate that surgical treatment can be safely performed even after HDC with HSCT if attention is paid to myelosuppression and the adverse effects of both chemotherapeutic agents and immunosuppressants.
    European Journal of Pediatric Surgery 08/2014; · 0.84 Impact Factor
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    ABSTRACT: In pediatric LDLT, graft reduction is sometimes required because of the graft size mismatch. Dividing the portal triad and hepatic veins with a linear stapler is a rapid and safe method of reduction. We herein present a case with a left lateral segment reduction achieved using a linear stapler after reperfusion in pediatric LDLT. The patient was a male who had previously undergone Kasai procedure for biliary atresia. We performed the LDLT with his father's lateral segment. According to the pre-operative volumetry, the GV/SLV ratio was 102.5%. As the patient's PV was narrow, sclerotic and thick, we decided to put an interposition with the IMV graft of the donor between the confluence and the graft PV. The graft PV was anastomosed to the IMV graft. The warm ischemic time was 34 min, and the cold ischemic time was 82 min. The ratio of the graft size to the recipient weight (G/R ratio) was 4.2%. After reperfusion, we found that the graft had poor perfusion and decided to reduce the graft size. We noted good perfusion in the residual area after the lateral edge was clamped with an intestinal clamp. The liver tissue was sufficiently fractured with an intestinal clamp and then was divided with a linear stapler. The final G/R ratio was 3.6%. The total length of the operation was 12 h and 20 min. The amount of blood lost was 430 mL. No surgical complications, including post-operative hemorrhage and bile leakage, were encountered. We believe that using the linear stapler decreased the duration of the operation and was an acceptable technique for reducing the graft after reperfusion.
    Pediatric Transplantation 06/2014; 18(6):E197-E199. · 1.50 Impact Factor
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    ABSTRACT: The use of thoracoscopy and laparoscopy in the treatment of congenital diaphragmatic hernias (CDHs) has been recently reported; however, the use of these procedures still remains controversial due to CO(2) insufflation and limited working space. In addition, because of difficult techniques, it has not been widely accepted. Among CDH patients, mild cases whose lung is not hypoplastic, and not associated with persistent pulmonary hypertension of the neonate (PPHN) often develop small defects in the diaphragm that can be repaired using "direct closure." Because direct closure does not require as wide an operative field as that needed for patch closure, we repaired CDH through umbilical skin windows in two neonates with mild CDH to minimize the wounds. With the creation of additional radical small incisions, the surgeries were successfully performed without any intra- or postoperative complications, and the wounds were cosmetically pleasing. The repair of CDHs through umbilical skin windows is a feasible and useful approach in neonates with mild CDH.
    Pediatric Surgery International 05/2013; 29(5):529-32. · 1.22 Impact Factor
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    ABSTRACT: Background Survivin, an inhibitor of apoptosis, has been reported to be associated with a worse prognosis in some malignancies. However, its expression in hepatoblastoma (HB) remains to be elucidated. We assessed the survivin expression in HB specimens collected before and after chemotherapy to elucidate the impact of survivin on the outcome of HB therapy.Methods HB specimens were collected before and after 2 to 4 cycles of cisplatin-based chemotherapy from 16 patients. The survivin expression level was assessed by immunohistochemical staining and real-time polymerase chain reaction.Results Out of 16, 12 HB sections collected before chemotherapy were positive for survivin as determined by immunohistochemical staining. The intensity of survivin expression was found to significantly increase after chemotherapy. Surprisingly, all of the HB specimens obtained after chemotherapy were positive for survivin. The expression of survivin messenger ribonucleic acid from a human HB cell line, Huh-6 was significantly higher when the cells were cultured with cis-diamminedichloroplatinum(II) than when the cells were cultured without the drug.Conclusion Our results indicate that most of the primary HB tissue specimens express survivin, and its expression increased after chemotherapy, thus suggesting that survivin may concern with the survival of tumor cells, therefore be a candidate for the target of the treatment of HB.
    European Journal of Pediatric Surgery 02/2013; · 0.84 Impact Factor
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    ABSTRACT: To evaluate the long-term quality of life (QOL) of patients who had undergone major neonatal surgery, the psychosocial and cognitive consequences of neonatal surgical stress were assessed when the patients reached school age. Seventy-two patients who had undergone major neonatal surgery were enrolled in this study. Their primary diseases were anorectal malformation (ARM) in 27 cases, esophageal atresia (EA) in 23, and congenital diaphragmatic hernia (CDH) in 22. Intelligence tests using Wechsler Intelligence Scale for Children III (WISC-III) or a developmental test and the Child Behavior Checklist were conducted through questionnaires and interviews with clinical psychologists. Mental retardation (MR) was apparent in 25% of EA, 20% of ARM, and 18% of CDH, significantly higher than the 2% to 3% commonly found in the general population. The clinical range (CR) of the Child Behavior Checklist was seen in 35% of EA, 59% of ARM, and 38% of CDH, which is also significantly higher than the 25% typically seen in the general population. No significant differences in MR and CR were seen among the primary diseases. The most important factors influencing MR and CR remain to be identified. To ensure true quality of life after neonatal surgical stress, pediatric surgeons must consider not only physical assessments but also cognitive, emotional, and psychosocial assessments.
    Journal of Pediatric Surgery 12/2011; 46(12):2250-3. · 1.38 Impact Factor
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    ABSTRACT: To evaluate the effectiveness of VQZ plasty, we analyzed our experience with continent catheterizable urinary stomas using VQZ plasty and V-flap techniques. We retrospectively reviewed the records of 25 patients who underwent Mitrofanoff procedures in 2000-2009. All stomas were created in the lower quadrant. There were 10 patients who underwent VQZ plasty and 15 in whom the V-flap technique was used. The stomal complications of these two groups were compared. Two patients (20%) with VQZ plasty and five (33.3%) with V-flap required surgical revision. Hypertrophic mucosae that excreted mucus and blood periodically were resected in two patients (13.3%) with V-flap. One patient (10%) with VQZ plasty had a surgical site infection. Although the stomal complication rate was lower in patients with VQZ plasty compared to those with V-flap, this difference was not statistically significant (P = 0.4). Our results show a tendency towards decreased stomal complications rates in patients with VQZ plasty, suggesting its superiority over the V-flap technique because of good cosmesis. To successfully construct VQZ stomas, surgeons should work to preserve the blood supply of skin flaps and reduce the subcutaneous dead space, and thus reduce the risk of surgical site infection.
    Journal of pediatric urology 08/2011; 7(4):433-7. · 1.38 Impact Factor
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    ABSTRACT: We report an extremely rare case of dermatofibrosarcoma protuberans located on the face of an 8-year-old boy. Although dermatofibrosarcoma protuberans typically has intermediate malignancy, the tumor in the present case was highly invasive and required a multistaged operation, including wide resection and full-thickness skin grafting. These operations were successfully performed, and the patient is alive without recurrence for 7 years.
    Journal of Pediatric Surgery 07/2011; 46(7):1438-41. · 1.38 Impact Factor
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    ABSTRACT: We determined the incidence of acquired undescended testes in boys with hypospadias. We retrospectively reviewed the records of 566 boys with hypospadias who were referred to our outpatient clinic between January 2000 and September 2009. Acquired undescended testes were defined as testes that were documented at the bottom of the scrotum at least once after birth by the pediatric urologist at our institution but were subsequently documented to have moved from a satisfactory scrotal position by the same pediatric urologist or an equally experienced pediatric urologist. However, this definition did not include undescended testes after inguinoscrotal surgery. We excluded boys with gender development disorders with testicular dysgenesis, those who underwent bilateral inguinoscrotal surgery and those without congenital cryptorchidism who were followed less than 3 months. Of the 566 boys with hypospadias 100 met study exclusion criteria. Of the 466 boys included in analysis 29 (6.2%) had congenital cryptorchidism and 15 (3.2%) had acquired undescended testes. Urethroplasty was performed in 413 boys, including 91 with distal, 132 with mid and 181 with proximal hypospadias. The incidence of congenital cryptorchidism and acquired undescended testes in boys with proximal hypospadias was significantly higher than that in boys with other types of hypospadias (p = 0.03 and 0.001, respectively). Boys with proximal hypospadias are at a higher risk for acquired undescended testes than those with other mild types of hypospadias. Thus, testicular location should be monitored regularly until after puberty.
    The Journal of urology 06/2011; 185(6 Suppl):2440-3. · 3.75 Impact Factor
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    ABSTRACT: A nationwide survey on neonatal surgery conducted by the Japanese Society of Pediatric Surgeons has demonstrated that the mortality of neonatal intestinal perforation has risen over the past 15 years. The incidence of intestinal perforation in extremely low-birthweight (ELBW) neonates has been increasing as more ELBW neonates survive and as the live-birth rate of ELBW has increased. In contrast to necrotizing enterocolitis (NEC) and focal intestinal perforation (FIP), the pathogenesis of meconium-related ileus, defined as functional bowel obstruction characterized by delayed meconium excretion and microcolon, remains unclarified. The histology of 13 ELBW neonates with intestinal perforation secondary to meconium-related ileus was reviewed, and the radiology of 33 cases of meconium-related ileus diagnosed on contrast enema was reviewed. Specimens obtained from 16 ELBW neonates without gastrointestinal disease served as age-matched controls for histological assessment. The size of the ganglion cell nucleus in meconium-related ileus and in control subjects was 47.3 ± 22.0 µm(2) and 37.8 ± 11.6 µm(2), respectively, which was not significantly different. In all cases of meconium-related ileus, contrast enema demonstrated a microcolon or small-sized colon, with a gradual caliber change in the ileum and filling defects due to meconium in the ileum or colon, showing not-identical locations of caliber changes and filling defects. Morphological immaturity of ganglia was not suggested to be the pathogenesis of meconium-related ileus. Impaction of inspissated meconium is not the cause of obstruction, but the result of excessive water absorption in the hypoperistaltic bowel before birth, although the underlying mechanism responsible for the fetal hypoperistalsis remains unclear.
    Pediatrics International 04/2011; 53(6):887-91. · 0.88 Impact Factor
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    ABSTRACT: To describe the clinical features of children with ovotesticular disorder of sex development (DSD) and to review cases of ovotesticular DSD in Japan. Medical records of eight children diagnosed with ovotesticular DSD at our institute during the past 17 years were retrospectively evaluated. A review of 165 reported cases of ovotesticular DSD from Japanese institutions was carried out. Mean follow up was 8.2 years for six children, with two children lost to follow up. Mean age at first presentation was 2.4 months. All children were Japanese. The most common initial manifestation was ambiguous genitalia. The female:male ratio as the sex of rearing was 1:1. Gender reassignment, from male to female, was carried out in one child at 4-months-old. Genital surgery was always carried out in early childhood as per family desire. Appropriate gonadal tissue was preserved except for one child. No gonadal tumors were detected during follow up. Spontaneous pubertal development occurred in one boy. In reviewing Japanese data, the frequency of testes was higher than in other ethnicities and this was related to the higher incidence of 46,XY. According to our experience, most families in Japan desire early genital surgery in the case of ovotesticular DSD. Chromosomal and gonadal distributions in patients with ovotesticular DSD differ between Japanese and other ethnic groups. Treatment for these patients needs to be provided after considering the cultural and social backgrounds of DSD in Japan.
    International Journal of Urology 03/2011; 18(3):231-6. · 1.73 Impact Factor
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    ABSTRACT: The aim of this study is to evaluate our therapeutic strategy for persistent cloaca from the viewpoint of long-term functional outcome. This study covers 17 cases of persistent cloaca treated at our institution and followed for more than 3 years. As a definitive repair for anorectal and urogenital systems, simultaneous surgery with posterior sagittal approach or anorecto-urethrovagino-plasty (PSARUVP) was performed. The length of the common channel and the shape of the vagina determined the vaginoplasty methods. Fecal function was assessed with the scoring system of the Japan Study Group of Anorectal Anomalies. Anorectoplasty was performed with the posterior sagittal approach in 15 cases and with the perineal approach in two. Vaginoplasty was performed with total urogenital mobilization in nine cases, rectal interposition in four, vaginal flap in two and with other methods. Fecal function was classified as good in three cases, moderate in ten, and poor in four. In the poor cases, Malone's antegrade continence enema (MACE) was performed, which improved fecal function significantly. PSARUVP might be the optimal surgery for persistent cloaca at present; however, satisfactory fecal function could not be achieved in those cases with a longer common channel. MACE effectively compensated for the poor outcome and was especially successful at eliminating incontinence.
    Pediatric Surgery International 01/2011; 27(5):505-8. · 1.22 Impact Factor
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    ABSTRACT: Although it has been suggested that the MYCN oncoprotein functions may influence tumorigenesis and patient survival in neuroblastoma, the mechanism of these functions remains unclear. To elucidate such molecular and biological mechanisms, we performed knock-down of MYCN expression using RNA interference (RNAi) method. MYCN-siRNAs (MYCN-siRNA) were transfected into the MYCN-amplified cell line NB-1. To verify the sequence specificity of the siRNA, we prepared three control groups (siRNA control group: siRNAs with no significant homology to any known sequences in human genome, mock control group: reagent and PBS, and the untransfected control group). The cells were analyzed by real-time RT-PCR, Western blotting, immunocytochemistry for gene expression. Cell proliferation activity was measured by WST-1 assay. TUNEL staining was performed to evaluate apoptosis. After the MYCN-siRNA transfection, the expression level of the MYCN mRNA was significantly reduced to 30% of those of the three control groups (p<0.05). Western blotting revealed an obvious reduction in MYCN protein level in the MYCN-siRNA group. On immunocytochemistry, intensity of nuclear staining of MYCN was weaker in the MYCN-siRNA group than in the three control groups. On WST-1 viability assay, cell proliferation after the MYCN-siRNA transfection was significantly suppressed compared to the three control groups (p<0.05). The TUNEL positive cells were frequently observed in the MYCN-siRNA group. Additionally, after the MYCN-siRNA transfection, the morphologic change which was suggestive of neuronal cell differentiation was observed and TrkA and TrkC expressions were also significantly up-regulated. Using RNAi method, the knock-down of MYCN expression induced growth-inhibition, apoptotic activity and cell differentiation in MYCN-amplified NB-1 cell line.
    International Journal of Oncology 05/2007; 30(5):1189-96. · 2.66 Impact Factor
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    ABSTRACT: Recent evidence suggests an association between up-regulation of beta-catenin/Wnt signaling pathway and neuronal differentiation of neuroblastoma. We overexpressed beta-catenin into a human neuroblastoma cell line NB-1 and observed its effect on cellular morphology, growth potential and alteration in a known differentiation related gene, trkA. Expression plasmids containing wild-type and mutated forms of beta-catenin gene were transfected into NB-1 cells, using liposome-based transfection method. The mutated forms were a deletion of three nucleotides of codon 45 and a large deletion involving the whole exon 3. In the transient transfection model, cell viability assay demonstrated significant negative effect of mutated beta-catenin transfection, but not wild-type, on the cell proliferation. To investigate impacts of beta-catenin overexpression in detail, a stable transfection model was established. Clones with comparable expression of beta-catenin at the mRNA level were selected. Only the selected clones with mutated form of beta-catenin exhibited neurite extension pattern and stunned cell proliferation, in association with higher accumulation of total cellular beta-catenin protein as evidenced by Western blot and immunocytochemistry. Cell cycle progression demonstrated significantly higher G0-G1 fraction in each stable cell clone with beta-catenin expression plasmid. In addition, retarded G1/S transition was observed exclusively in the cell clones with mutated form. Concomitantly with overexpressed beta-catenin, up-regulations of trkA and Ha-ras were also identified. Our study suggests a potential availability of beta-catenin/Wnt signaling pathway as a target of molecular manipulation for treatment of high-risk neuroblastoma and a potential association between the pathway and the trkA/neurotrophin cascades.
    Oncology Reports 01/2007; 16(6):1197-203. · 2.30 Impact Factor
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    ABSTRACT: Undifferentiated (embryonal) sarcoma of the liver (USL) is a rare hepatic tumor in children. Its pathogenesis is largely unknown, but lines of evidence suggest common links to that of mesenchymal hamartoma of the liver (MH). Previously, we found a p53 mutation in a case of pediatric USL. Recently, there was another published report, demonstrating further evidence of p53 alterations in the adult cases. In this study, we analyzed in three cases of pediatric USL and two cases of MH by using PCR-SSCP and direct sequencing technique. The study identified missense mutations in all three cases of USL, but none of MH. The mutations were found specifically in tumor tissue and not detected in the surrounding normal hepatic tissue. Mutation points were localized in exon 7 (Gly245Ser), exon 6 (Arg196Pro), and exon 8 (Arg273Pro), respectively. Immunohistochemical study of p53 protein expression revealed strong immunoreactivity in cases of USL and negative staining in MH. In summary, this study provided a novel data suggesting that mutations of p53 in pediatric USL are not random genetic events and highly possible to be involved in its tumorigenesis.
    Hepatology Research 09/2006; 35(4):229-34. · 2.07 Impact Factor
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    ABSTRACT: Feasibility of duct-to-duct biliary reconstruction in adult living related liver transplantation (LRLTx) has been recently reported; however, little has been known of its surgical outcome in children. To assess the feasibility and safety of duct-to-duct biliary reconstruction in children, the surgical outcomes of duct-to-duct biliary reconstruction were retrospectively analyzed. The subjects were three children who underwent LRLTx in our hospital each utilizing allografts with a right lobe, a left robe and a lateral segment, respectively. The cause of end-stage liver disease in each of them was fulminant Wilson's disease, fulminant hepatic failure and unresectable hepatoblastoma. Duct-to-duct anastomosis was performed in younger patients and adolescents with interrupted and continuous sutures, respectively. The diameter of bile duct in allografts was from 4 to 6 mm and 12 or 13 stitches were required for anastomosis. Post-operative choledochography from the external tube showed neither stenosis nor leakage and the tube was evacuated within 3 months after LRLTx. No biliary complications were observed with the median follow-up of 28 months. In conclusion, our results show that duct-to-duct biliary reconstructions in pediatric LRLTx seemed to be feasible and safe. Further studies are required to elucidate its real impact on pediatric LRLTx.
    Pediatric Transplantation 04/2006; 10(2):248-51. · 1.50 Impact Factor
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    ABSTRACT: Mutations of beta-catenin have been identified in the majority of pediatric hepatic malignancies, including hepatoblastoma (HB) and hepatocellular carcinoma (HCC), suggesting its important contribution in hepatic tumorigenesis in this age group. However, the role of beta-catenin/canonical Wnt signaling pathway in the neoplastic growth of cancer cells has not been directly studied. To address beta-catenin's capability in maintaining the malignant phenotype in established pediatric HB and HCC cell lines, HuH-6 and HepG2, harboring mutated and overexpressed beta-catenin, we carried out a series of in vitro analyses through a transfection of short interfering RNAs (siRNAs) to generate a loss-of-function model. HuH-7, another HB cell line derived from a pediatric patient without a stabilizing mutation was used for comparison. RNA interference successfully manipulated the degradation of overexpressed beta-catenin. In all cell lines, beta-catenin mRNA was suppressed by 80-90% after 48 h of transfection, and a reduction of its protein expression was demonstrated. In HuH-6 and HepG2, the pre-existing beta-catenin nuclear accumulation disappeared and reductions of beta-catenin downstream target genes, c-myc and cyclinD1, were also evidenced after the treatment. The in vitro proliferation of both cell lines was transiently inhibited. In contrast, the suppression of beta-catenin in HuH-7 did not lead to a significant change in the expression of target genes or cellular proliferation. Our data indicate that beta-catenin can be considered a specific target for gene therapy in pediatric hepatic tumors with mutations and overexpression of this gene.
    International Journal of Oncology 04/2006; 28(3):715-22. · 2.66 Impact Factor
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    ABSTRACT: The authors report on a child with tracheoesophageal fistula secondary to disc battery ingestion. Through a low cervical collar incision with limited sternal split, the fistula was primarily repaired, and the omohyoid muscle and thymus were mobilized to cover the suture lines. There are no signs of recurrent fistula 6 months after the operation. The anterior cervical approach with limited sternal split provided excellent access to the fistula. To the authors' knowledge, this is the first report of successful primary repair of a tracheoesophageal fistula secondary to disk battery ingestion.
    Journal of Pediatric Surgery 03/2004; 39(2):243-4. · 1.38 Impact Factor
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    ABSTRACT: The incidence of hepatoblastoma (HB) in children of low birth weight is increasing. In the authors' institute, 5 infants of extremely low birth weight (ELBW) were found to have HB. The purpose of this study was to identify the characteristics of these infants to elucidate the pathogenesis of HB arising in ELBW infants. Birth weight (BW) ranged from 554 to 750 g (mean, 654 g) and gestational age from 23 to 29 weeks (mean, 25.8 weeks). Medical records of the 5 patients were reviewed, and perinatal treatments were compared with those of ELBW infants without HB. One patient with intraabdominal hemorrhage had emergency operation, which was followed by early postoperative death. The parents of one child refused treatment because of associated severe anomalies. He died of the growing tumor 4 months after diagnosis. The remaining 3 patients had radical operation performed after intraarterial chemoembolization and systemic chemotherapy. One died of hepatic failure 7 months after operation. Two are alive 5 and 9 months after operation. The incidence of HB among ELBW infants was estimated to be about 0.5% in our institute. The mean durations of mechanical ventilation, oxygen inhalation, and hospitalization during the neonatal periods in cases of HB were significantly longer than those in BW matched control infants (P <.01). ELBW children have a high risk for HB. In follow-up of ELBW infants, serum alpha-fetoprotein or abdominal ultrasonography may be useful to detect early HB. The children with HB received perinatal treatments for a significantly longer time, which suggests that perinatal intensive and long-term medical treatments may be involved in the tumorigenesis in the highly sensitive immature liver.
    Journal of Pediatric Surgery 01/2003; 38(1):134-7; discussion 134-7. · 1.38 Impact Factor
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    ABSTRACT: The feasibility of oral administration of tacrolimus in the presence of an intestinal stoma after liver transplantation (LTx) has not been adequately demonstrated. A 10-month-old girl underwent LTx with biliary reconstruction using a Roux-en Y loop. She developed intestinal perforation and underwent a jejunostomy at 40-50 cm distal to the jejunojejunostomy of the Roux-en Y loop on day 8 post-LTx. Tacrolimus was given twice daily via a nasogastric tube or orally; the initial dose of tacrolimus was 0.10 mg/kg/day. Until the time of intestinal perforation, the trough level of tacrolimus ranged from 13.0 to 19.6 ng/mL. The dose-normalized trough concentration (DNTC) of tacrolimus ranged from 130 to 196 per mg.mL (control: 80-145 per mg.mL). For a 2-week period when the patient was septic, the tacrolimus dose was reduced to 0.05 mg/kg/day, with a subsequent trough level of 3.6-5.1 ng/mL (DNTC: 72-102 per mg.mL). After 3 weeks, the dose was increased to 0.175 mg/kg/day with the disappearance of infection; the trough level ranged from 8.5 to 9.7 ng/mL with a peak level of 26.3 ng/mL (DNTC: 48.5-55.4 per mg.mL). After the initiation of oral feeding, the dose was slightly increased to 0.20 mg/kg/day with the trough level ranging from 8.1 to 9.8 ng/mL (DNTC: 40.5-49 per mg.mL). After closure of the jejunostomy, the dose of tacrolimus was reduced to 0.075 mg/kg/day to maintain the same trough level (7.9-9.1 ng/mL) and the DNTC ranged from 105 to 121 per mg.mL. In conclusion, oral administration of tacrolimus may achieve the therapeutic level, even in the presence of jejunostomy after LTx, although the bioavailability is decreased.
    Pediatric Transplantation 07/2001; 5(3):204-9. · 1.50 Impact Factor

Publication Stats

110 Citations
32.41 Total Impact Points


  • 2006–2014
    • Osaka City University
      • Department of Pediatrics
      Ōsaka, Ōsaka, Japan
    • Prince of Songkla University
      Amphoe Muang Songkhla, Songkhla, Thailand
  • 2006–2013
    • Osaka University
      • Division of Pediatric Surgery
      Ibaraki, Osaka-fu, Japan
  • 2011
    • Osaka Medical Center and Research Institute for Maternal and Child Health
      Izumi, Ōsaka, Japan