Kyushu University Academic Staff Educational and Research Activities Database
List of Papers
Tatsuro Tajiri Last modified date:2023.12.06

Professor / Pediatric Surgery / Department of Clinical Medicine / Faculty of Medical Sciences

1. Beckwith-Wiedemann Syndrome (EMG Syndrome) Observed in Three Cases With Antenatally Diagnosed Omphaloceles
We experienced three typical cases of Beckwith-Wiedemann sundrome (EMG syndrome) . In common to three cases, omphalocele was antenatally found. At birth, the large statue for gastational age, the macroglossia and hypoglycemia were recognized. Type of omphalocele was a hernia into the umbilical cords and primary repair was performed on the first post-natal day in all three cases. Degree of hypoglycemia varied considerably among patients and a proper intravenous glucose infusion was necessary in each case. Three cases are alive without development of malignancies and now became 11-year-old, 7-year-old, 8-month-old, respectively. In antenatally diagnosed cases with omphalocele, association of Beckwith-Wiedemann syndrome should be carefully investigated to prevent irreversible hypoglycemia and to follow up the organ carcinogenesis..
2. T. Taguchi, Y. Shima, M. Nakao, Y. Fujii, T. Tajiri, K. Ogita, S. Suita, Activation of immediate early genes in relation to proliferation and apoptosis of enterocytes after ischemia-reperfusion injury of small intestine, Transplantation Proceedings, 10.1016/S0041-1345(02)02728-8, 34, 3, 983, 2002.05.
3. A Case of Endobronchial Leiomyoma Detected by Refractory Atelectasis
We experienced a 6-year-old boy with leiomyoma of the right intermediate bronchus detected by refractory atelectasis accompanying congenital immunodeficiency (lack of C_2, C_9).The preoperative bronchoscope findings revealed that the tumor, found at the right intermediate bronchus, obstructed the right middle and lower lobes. We successfully performed a complete tumor resection of the right middle and lower lobectomy. The patientis alive with no disease at 5 months postoperatively. Leiomyoma of the bronchus has been rarely reported in childhood. The relationship between leiomyoma and the congenital immunodeficiency is still unknown. A careful long follow up for such a case is necessary..
4. Hiroki Kai, Takeshi Shono, Tatsuro Tajiri, Sachiyo Suita, Long-term effects of intrauterine exposure to mono-n-butyl phthalate on the reproductive function of postnatal rats, Journal of Pediatric Surgery, 10.1016/j.jpedsurg.2004.10.009, 40, 2, 429-433, 2005.02, Purpose: Although it is well known that phthalate esters induce testicular dysfunction in both adult and immature rats, there have been few reports on the long-term effect of phthalate esters on the testicular function of male rats exposed to phthalate esters in utero. This study was designed to assess the long-term effects of the mono-n-butyl phthalate (MBP) ester on the testicular function of neonatal and adult rat offspring from pregnant dams exposed to phthalate esters during gestation. Methods: Pregnant rats were administered MBP [0.5 g/(kg body weight/•d)
4 days] by gavage from the 15th to the 18th gestational day. Rats administered solvent only were used as control subjects. After the rats' puberty, using male pups whose testes descended normally, the authors examined their fertility while also measuring their testicular weights, mean seminiferous tubular diameter, and the developmental grade of the germ cells (Johnsen score) in their testes. Next, in neonatal rats, the authors measured the testicular concentration of the Mullerian inhibiting substance (MIS) protein using enzyme-linked immunoassay and the expression level of the MIS messenger RNA using the quantitative polymerase chain reaction method as a marker of the Sertoli cells' function. Next the concentration of testosterone protein using a radioimmunoassay as a marker of the Leydig cells' function was measured. Results: The pregnancy rate of the female rats coupled with MBP-treated male rats decreased significantly in comparison with that of the female rats coupled with control male rats (P &lt
. 01). Both the testicular weight and the Johnsen score in the MBP-treated group were decreased significantly more than those of the control group (P &lt
. 05). Neither the concentration of the MIS protein nor the expression level of the MIS messenger RNA in the MBP-treated neonatal testes differed from those of the control testes, whereas the concentration of testosterone protein in the neonate testes decreased significantly in the MBP-treated group in comparison with that of the control group (P &lt
. 01). Conclusions: A prenatal short-time exposure to MBP induces a long-term effect on postnatal rats and impairs reproductive function in male offspring probably by inhibiting the Leydig cells' rather than Sertoli cells' function in the fetal period. © 2005 Elsevier Inc. All rights reserved..
5. Hiyama Eiso, Hayashi Yutaka, Fukuzawa Masahiro, Sasaki Fumiaki, Sugiyama Masahiko, Kondo Satoshi, Tajiri Tatsuro, Yoneda Akihiro, Akazawa Kouhei, Ohtaki Megu, IS-3 Heterogeneous subgroups in human neuroblastoma for clinically relevant risk stratification(International Session1), 日本小児外科学会雑誌, 10.11164/jjsps.42.3_379, 42, 3, 379-379, 2006.03.
6. Salem Mohamed, Kinoshita Yoshiaki, Tajiri Tatsuro, Souzaki Ryota, Tatsuta Kyosuke, Higashi Mayumi, Izaki Tomoko, Taguchi Tomoaki, IS-2 Association between Her 2 expression and histological differentiation of Wilms tumor(International Session1), 日本小児外科学会雑誌, 10.11164/jjsps.42.3_378, 42, 3, 378-378, 2006.05.
7. S-044 The role of surgical intervention in the treatment for neuroblastoma(Frontier of pediatric oncology I, the 44th Annual Meeting of Japanese Society of Pediatric Surgeons).
8. P-208A Clinical experience of immunotherapy utilizing dendritic cell against pediatric renal cell carcinoma(Oncology 3, the 44th Annual Meeting of Japanese Society of Pediatric Surgeons).
9. P-200A Evaluating system for MYCN amplification : Southern blot, Quantitative PCR, FISH, Microdissection(Oncology 2, the 44th Annual Meeting of Japanese Society of Pediatric Surgeons).
10. P-198A The clinical feature of 12- to 24-months-old children with neuroblastoma in 6-months screening era in Japan(Oncology 1, the 44th Annual Meeting of Japanese Society of Pediatric Surgeons).
11. B-024 Clinicopathological analysis of inflammatory pseudotumor and inflammatory myofibroblastic tumor(Oncology, the 44th Annual Meeting of Japanese Society of Pediatric Surgeons).
12. B-008 Risk and benefit of initial radical operation and preoperative chemotherapy for the treatment of Wilms' tumor(Oral Presentation Oncology 2,Better Life for Sick Children, Better Future for Pediatric Surgery,the 45th Annual Meeting of Japanese Society of Pediatric Surgeons).
13. B-004 Analysis of clinical and biological characteristics of neuroblastoma detected after ending of mass screening(Oral Presentation Oncology 1,Better Life for Sick Children, Better Future for Pediatric Surgery,the 45th Annual Meeting of Japanese Society of Pediatric Surgeons).
14. B-001 Clinical implications of the slight increase in the gene dosage of MYCN determined by quantitative PCR in neuroblastoma(Oral Presentation Oncology 1,Better Life for Sick Children, Better Future for Pediatric Surgery,the 45th Annual Meeting of Japanese Society of Pediatric Surgeons).
15. A Case Report of Intestinal Mesenteric Hernia in a Neonate
A 30-day-old boy was admitted to our hospital due to frequent vomiting that had persisted for 7 hours and unconsciousness. His abdomen was moderately dilated and there was a muscular rigidity on palpation. Laboratory data showed increasing leukocytosis, metabolic acidosis, hyperkalemia, and hyperglycemia. The abdominal X-ray showed a marked distension of the intestine in the upper abdomen. The abdominal ultra-sonography revealed dilated and thickened intestine with no peristalsis, and a small amount of ascites. Preoperative diagnosis was strangulated ileus of unknown origin. An emergent operation revealed a part of the ileum (120cm in length) was incarcerated into the defect (2cm in diameter) in the mesentery at the terminal ileum. The necrotic intestine was resected and mesenteric defect was closed. The postoperative course was uneventful and he was discharged 15 days after the operation. Although the intestinal mesenteric hernia is relatively rare, it should be included in a differential diagnosis of acute abdomen in neonates because it could be fatal unless emergent surgery is properly performed..
16. K. Tatsuta, S. Tanaka, T. Tajiri, S. Shibata, A. Komaru, Y. Ueda, M. Inoue, M. Hasegawa, S. Suita, K. Sueishi, T. Taguchi, Y. Yonemitsu, Complete elimination of established neuroblastoma by synergistic action of γ-irradiation and DCs treated with rSeV expressing interferon-β gene, Gene Therapy, 10.1038/gt.2008.161, 16, 2, 240-251, 2009.02, Dendritic cell (DC)-based immunotherapy has been investigated as a new therapeutic approach to intractable neuroblastomas
however, only limited clinical effect has been reported. To overcome the relatively low sensitivity of neuroblastomas against immunotherapy, we undertook a preclinical efficacy study to examine murine models to assess the combined effects of γ-irradiation pretreatment and recombinant Sendai virus (ts-rSeV/dF)-mediated murine interferon-β (mIFN-β) gene transfer to DCs using established c1300 neuroblastomas. Similar to intractable neuroblastomas in the clinic, established c1300 tumors were highly resistant to monotherapy with either γ-irradiation or DCs activated by ts-rSeV/dF without transgene (ts-rSeV/dF-null) that has been shown to be effective against other murine tumors, including B16F10 melanoma. In contrast, immunotherapy using DCs expressing mIFN-β through ts-rSeV/dF (ts-rSeV/dF-mIFNβ-DCs) effectively reduced tumor size, and its combination with γ-irradiation pretreatment dramatically enhanced its antitumor effect, resulting frequently in the complete elimination of established c1300 tumors 7-9mm in diameter, in a high survival rate among mice, and in the development of protective immunity in the mice against rechallenge by the tumor cells. These results indicate that the combination of ts-rSeV/dF-mIFNβ-DCs with γ-irradiation is a hopeful strategy for the treatment of intractable neuroblastomas, warranting further investigation in the clinical setting..
17. Teshiba Risa, Yamamoto Ken, Kinoshita Yoshiaki, Masumoto Kouji, Tajiri Tatsuro, Sumitomo Kenzo, Taguchi Tomoaki, IS2-06 Whole-Genome SNP linkage analysis in a familial multinodular goiter(Neoplasm,Share Smiles with Sick Children, Dreams and Innovation for Pediatric Surgery), 日本小児外科学会雑誌, 10.11164/jjsps.46.3_468, 46, 3, 468-468, 2010.05.
18. Hayato Fujita, Kenoki Ohuchida, Kazuhiro Mizumoto, Soichi Itaba, Tetsuhide Ito, Kohei Nakata, Jun Yu, Tadashi Kayashima, Ryota Souzaki, Tatsuro Tajiri, Tatsuya Manabe, Takao Ohtsuka, Masao Tanaka, Gene expression levels as predictive markers of outcome in pancreatic cancer after gemcitabine-based adjuvant chemotherapy, Neoplasia, 10.1593/neo.10458, 12, 10, 807-817, 2010.10, Background Andaims: The standard palliative chemotherapy for pancreatic ductal adenocarcinoma (PDAC) is gemcitabine-based chemotherapy
however, PDAC still presents a major therapeutic challenge. The aims of this study were to investigate the expression pattern of genes involved in gemcitabine sensitivity in resected PDAC tissues and to determine correlations of gene expression with treatment outcome. Materials And Methods: We obtained formalin-fixed paraffin-embedded (FFPE) tissue samples from 70 patients with PDAC. Of the 70 patients, 40 received gemcitabine-based adjuvant chemotherapy (AC). We measured hENT1, dCK, CDA, RRM1, and RRM2 messenger RNA (mRNA) levels by quantitative real-time reverse transcription-polymerase chain reaction and determined the combined score (GEM score), based on the expression levels of hENT1, dCK, RRM1, and RRM2, to investigate the association with survival time. By determining the expression levels of these genes in endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) cytologic specimens, we investigated the feasibility of individualized chemotherapy. RESULTS: High dCK (P =.0067), low RRM2 (P =.003), and high GEM score (P =.0003) groups had a significantly longer disease-free survival in the gemcitabine-treated group. A low GEM score (&lt
2) was an independent predictive marker for poor outcome to gemcitabine-based AC as shown by multivariate analysis (P =.0081). Altered expression levels of these genes were distinguishable in microdissected neoplastic cells from EUS-FNA cytologic specimens. Conclusions: Quantitative analyses of hENT1, dCK, RRM1, and RRM2 mRNA levels using FFPE tissue samples and microdissected neoplastic cells from EUS-FNA cytologic specimens may be useful in predicting the gemcitabine sensitivity of patients with PDAC. © 2010 Neoplasia Press, Inc..
19. Tajiri Tatsuro, Souzaki Ryota, Kinoshita Yoshiaki, Yosue Ryota, Taguchi Tomoaki, P-454 Surgical strategies for pediatric ovarian tumors, 日本小児外科学会雑誌, 10.11164/jjsps.47.4_558, 47, 4, 558-558, 2011.07.
20. A Case of Traumatic Main Pancreatic Duct Disruption Treated by External Drainage for Pancreatic Pseudocyst: a Review of 28 Cases Reported in Japan
Main pancreatic duct injury is rare in children and its therapeutic strategy is still controversial. Here, we report the case of a 6-year-old boy treated by only open drainage without distal pancreatectomy. He presented with abdominal pain after blunt abdominal trauma caused by a handlebar of a bicycle. An imaging study revealed main pancreatic duct injury with a giant pseudocyst, and he was transferred to our hospital 11 days after the onset of the injury. Endoscopic retrograde pancreatography (ERP) was performed, and cannulation into the pseudocyst was unsuccessful. On the day after ERP, he presented with acute abdominal pain with the rupture of the pseudocyst, requiring open drainage. His postoperative course was satisfactory and he was discharged 75 days after the onset with atrophy of the distal pancreas. Conservative management of pancreatic duct injury in children with or without drainage is associated with an extended hospital stay duration and the prolonged need for TPN. Operative management with pancreatic surgery could shorten the hospital stay but with the risk of surgical complications. Therefore, the choice of therapeutic strategy should depend on the patient's condition..
21. Comparison of Outcomes of Anterior Wrapping and Posterior Wrapping in Laparoscopic Fundoplication
Purpose: The operative method of fundoplication for gastroesophageal reflux disease (GERD) is divided into anterior wrapping (AW), such as Dor fundoplication, and posterior wrapping (PW), such as Toupet and Nissen fundoplications. Our institute introduced laparoscopic fundoplication in 2002. AW was performed until 2010, and PW has been performed since 2011. We examined the outcomes of AW and PW.
Methods: We examined 33 cases that we encountered from 2002 to 2013 and compared them retrospectively. The median age was 4 years (0-39 years), 26 patients were boys, and 7 were girls.
Results: Twenty-four patients showed severe motor and intellectual disabilities, six had congenital hiatal hernia, and three showed postoperative esophageal atresia. AW (Dor) was performed in 18 patients, and PW (Nissen fundoplication for 9 patients, Toupet fundoplication for 6 patients) was performed in 15 patients. Compared with AW (p Conclusions: In our institute, PW was found to be associated with significantly less operation time and intraoperative blood loss than AW. PW is a better procedure than AW for GERD. It was considered important to determine the condition of the patient in the selection of PW as the operative method. In particular, Nissen fundoplication is useful for patients with severe motor and intellectual disabilities..
22. Kanae Ogawa, Khaleque N Khan, Haruo Kuroboshi, Akemi Koshiba, Koki Shimura, Tatsuro Tajiri, Shigehisa Fumino, Hiroyuki Fujita, Tomoharu Okubo, Yoichiro Fujiwara, Go Horiguchi, Satoshi Teramukai, Akira Fujishita, Kyoko Itoh, Sun-Wei Guo, Jo Kitawaki, Taisuke Mori, Is neonatal uterine bleeding responsible for early-onset endometriosis?, Reproductive biology and endocrinology : RB&E, 10.1186/s12958-023-01099-1, 21, 1, 56-56, 2023.06, BACKGROUND: It has been hypothesized that the origin of early-onset endometriosis could be from endometrial mesenchymal stem cells (eMSCs) in neonatal uterine blood (NUB). There is no information on the possible mechanistic basis linking an association between NUB/neonatal endometrium and development of early-onset endometriosis. In this study we performed a series of experiments to clarify the mechanistic link between NUB and/or neonatal endometrium and development of early-onset endometriosis. METHODS: We retrospectively collected postmortem neonatal endometria (n = 15) and prospectively collected NUB (n = 18) of female babies for the analysis of different biological markers including eMSCs. Immunohistochemical analysis of neonatal endometria was performed to examine the expression patterns of ovarian steroid receptors (ER/PGR), decidualization (prolactin, IGFBP1), pre-decidualization (Glycodelin A, α-SMA), proliferation (Ki-67 index), vascularity (CD31 + cells), immunocompetent CD68+, CD45+, CD56 + cells and some putative markers of eMSCs. Cell transfer method and immunocytochemistry were used to investigate the eMSCs and/or endometrial cells in NUB. RESULTS: Immunohistochemical analysis of postmortem neonatal endometria revealed variable staining response to ER/PGR, decidual markers, and substantial proliferative and angiogenic activity. A moderate to strong immunoexpression of Glycodelin-A was found in both neonatal and adult endometria. The tissue infiltration of CD56+, CD45 + and CD68 + immunocompetent cells was significantly low in neonatal endometria than that in adult endometria (p = 0.0003, p 
23. 大平 美紀, 上條 岳彦, 瀧本 哲也, 中澤 温子, 松本 公一, 七野 浩之, 菱木 知郎, 家原 知子, 中村 洋子, 永瀬 浩喜, 米田 光宏, 福島 敬, 田尻 達郎, 中川原 章, 国際リスク分類システムと連携した神経芽腫分子生物学的データベースの構築と高リスク神経芽腫のゲノム解析(A retrospective study of 525 neuroblastoma cases by using updated follow-up data based on INRG variables(JCCG neuroblastoma committee: JNBSG)), 日本小児血液・がん学会雑誌, 53, 4, 223-223, 2016.11.
24. 大平 美紀, 七野 浩之, 久保 崇, 春田 雅之, 瀧本 哲也, 中澤 温子, 山崎 文登, 永瀬 浩喜, 田尻 達郎, 中川原 章, 市川 仁, 菱木 知郎, 上條 岳彦, 高リスク神経芽腫のがん遺伝子パネル解析(Genomic characterization of high-risk neuroblastoma by cancer panels), 日本癌学会総会記事, 78回, P-1176, 2019.09.
25. 大平 美紀, 七野 浩之, 久保 崇, 春田 雅之, 瀧本 哲也, 中澤 温子, 山崎 文登, 永瀬 浩喜, 田尻 達郎, 中川原 章, 市川 仁, 菱木 知郎, 上條 岳彦, 高リスク神経芽腫の小児がん用NCCオンコパネル解析, 日本癌学会総会記事, 79回, OE7-2, 2020.10.
26. 大平 美紀, 春田 雅之, 菅原 大樹, 七野 浩之, 菱木 知郎, 瀧本 哲也, 中澤 温子, 大喜多 肇, 東本 浩子, 牛島 俊和, 永瀬 浩喜, 市川 仁, 田尻 達郎, 中川原 章, 上條 岳彦, 日本小児がん研究グループ・神経芽腫委員会, 高リスク神経芽腫臨床試験例における各種ゲノムマーカーの後方視的解析, 日本癌学会総会記事, 80回, [J14-2], 2021.09.
27. 大平 美紀, 中村 洋子, 瀧本 哲也, 中澤 温子, 菱木 知郎, 松本 公一, 七野 浩之, 家原 知子, 永瀬 浩喜, 福島 敬, 米田 光宏, 田尻 達郎, 中川原 章, 上條 岳彦, 本邦で診断された神経芽腫605例の国際リスク分類マーカーの後方視的解析(Retrospective analysis of INRG clinical and genomic factors for 605 neuroblastomas in Japan), 日本癌学会総会記事, 81回, J-1067, 2022.09.
28. Jun Kono, Kouji Nagata, Keita Terui, Shoichiro Amari, Katsuaki Toyoshima, Noboru Inamura, Yuhki Koike, Masaya Yamoto, Tadaharu Okazaki, Yuta Yazaki, Hiroomi Okuyama, Masahiro Hayakawa, Taizo Furukawa, Kouji Masumoto, Akiko Yokoi, Noriaki Usui, Tatsuro Tajiri, The efficacy of the postnatal nasogastric tube position as a prognostic marker of left-sided isolated congenital diaphragmatic hernia, Pediatric Surgery International, 10.1007/s00383-022-05226-8, 38, 12, 1873-1880, 2022.09, PURPOSE: The prenatal diagnosis of the stomach position in congenital diaphragmatic hernia (CDH) has been a reliable prognostic factor, but few studies have focused on the postnatal position. We therefore evaluated the significance of the nasogastric (NG) tube position just after birth. METHODS: The Japanese CDH Study Group database enrolled 1037 CDH neonates over 15 years. In our multicenter retrospective study, 464 cases of left-sided isolated CDH with prenatal diagnoses were divided into two groups: NG tube below the diaphragm (BD; n = 190) or above the diaphragm (AD; n = 274). The primary outcome was the 90-day survival rate, and the secondary outcomes were mechanical ventilation duration, hospitalization duration, and recurrence rate. RESULTS: The BD group had a significantly higher 90-day survival rate (98.4 vs. 89.4%, p 
29. Hironori Goto, Yuhki Koga, Kenichi Kohashi, Hiroaki Ono, Junkichi Takemoto, Toshiharu Matsuura, Tatsuro Tajiri, Kenji Ihara, Yoshinao Oda, Shouichi Ohga, Pancreatoblastoma with a novel fusion gene of IQSEC1-RAF1., Pediatric blood & cancer, 10.1002/pbc.30155, 70, 4, e30155, 2022.12.
30. Kosuke Kambe, Masafumi Iguchi, Mayumi Higashi, Shigeki Yagyu, Shigehisa Fumino, Tsunao Kishida, Osam Mazda, Tatsuro Tajiri, Development of minimally invasive cancer immunotherapy using anti-disialoganglioside GD2 antibody-producing mesenchymal stem cells for a neuroblastoma mouse model., Pediatric surgery international, 10.1007/s00383-022-05310-z, 39, 1, 43-43, 2022.12, PURPOSE: Mouse IgG anti-disialoganglioside GD2 antibody-secreting mouse mesenchymal stem cells (anti-GD2-MSCs) were developed, and their anti-tumor effects were validated in an in vivo neuroblastoma mouse model. METHODS: Anti-GD2 antibody constructs were generated, incorporating FLAG-tagged single-chain fragment variables against GD2 fused to a linker sequence, and a fragment of a stationary portion was changed from human IgG to mouse IgG and GFP protein. The construct was lentivirally introduced into mouse MSCs. A syngeneic mouse model was established through the subcutaneous transplantation of a tumor tissue fragment from a TH-MYCN transgenic mouse, and the homing effects of anti-GD2-MSCs were validated by In vivo imaging system imaging. The syngeneic model was divided into three groups according to topical injection materials: anti-GD2-MSCs with IL-2, IL-2, and PBS. The tumors were removed, and natural killer (NK) cells were counted. RESULTS: Anti-GD2-MSCs showed homing effects in syngeneic models. The growth rate of subcutaneous tumors was significantly suppressed by anti-GD2-MSCs with IL-2 (p 
31. Jun Kono, Koichiro Yoshimaru, Toshiharu Matsuura, Akihiko Tamaki, Junkichi Takemoto, Shinya Matsumoto, Taeko Hotta, Kenichi Kohashi, Yoshinao Oda, Tatsuro Tajiri, COVID19 detection in appendix of acute appendicitis in a child: a case report and review of literature., Surgical case reports, 10.1186/s40792-023-01618-7, 9, 1, 37-37, 2023.03, BACKGROUND: Gastrointestinal symptoms are one of the most common presentations of Coronavirus disease-19 (COVID-19), even in children. Higher rates of complicated appendicitis have been demonstrated in the era of the COVID-19 outbreak, and it has been recently suggested that acute appendicitis may occur as a complication of COVID-19. However, the relationship between appendicitis and COVID-19 remains unclear. CASE PRESENTATION: A 7-year-old male presented to the pediatric emergency department with 2 days' history of lower abdominal discomfort and tenderness. On examination, his abdomen was distended with diffuse mild tenderness at the lower abdomen, which was aggravated by movement. He was also tested and was found to be positive for SARS-CoV-2. Computed tomography showed perforated appendicitis with a fecalith. The patient was admitted and laparoscopic appendectomy was successfully performed. Postoperatively, a minor intra-abdominal abscess was present, which successfully treated with antibiotics. Histopathology showed a markedly inflamed appendix with mucosal ulceration and transmural neutrophilic inflammation, which was consistent with phlegmonous appendicitis. Reverse transcription quantitative polymerase chain reaction using a surgically extracted appendix specimen revealed the presence of SARS-CoV-2 virus, which indicated a pathophysiological relationship between appendicitis and COVID-19. CONCLUSION: The present case will provide further understanding of pediatric patients with concomitant COVID-19 and acute appendicitis..
32. S Suita, T Tajiri, K Akazawa, Y Sera, H Takamatsu, H Mizote, H Ohgami, N Kurosaki, T Hara, J Okamura, S Miyazaki, T Sugimoto, K Kawakami, M Tsuneyoshi, H Tasaka, H Yano, H Akiyama, K Ikeda, Mass screening for neuroblastoma at 6 months of age: Difficult to justify, JOURNAL OF PEDIATRIC SURGERY, 33, 11, 1674-1678, 1998.11, Background/Purpose: A statistical analysis of the mass screening for neuroblastoma in Japan based on a population study rarely has been reported. This study aims to evaluate retrospectively the effectiveness of mass screening at 6 months of age using the available population data.
Methods:The data on the neuroblastoma cases registered by the Committee for Pediatric Solid Malignant Tumors in the Kyushu area were analyzed based on both screened and unscreened populations in the Kyushu area.
Results: From 1988 to 1992, the cumulative incidence of neuroblastoma in children less than 5 years of age was 82 in 484,599 for screened children, and 11 in 92,966 for unscreened children, respectively. Fourteen of the 82 screened patients had negative findings at 6 months of age (MS-negative cases). No significant difference was observed in the cumulative mortality rates from neuroblastoma in children younger than 5 years of age between the screened children and the unscreened children. Six of seven patients who died among the screened children were MS-negative cases with stage III or IV disease. In addition, no significant difference was found in the cumulative mortality rates from the neuroblastoma cases in patients less than 5 years of age between the children screened from 1988 to 1992 (7 of 484,599) and all children from 1980 to 1984 (14 of 668,084).
Conclusions: These findings suggests that the majority of the patients detected by mass screening had a favorable prognosis, and, mass screening in Japan for children less than 6 months of age was not observed to reduce the incidence and mortality from neuroblastoma. Therefore, mass screening at 6 months of age was not found to improve substantially the prognosis of patients with unfavorable neuroblastoma identified over 1 year of age, which is the primary purpose of such mass screening for neuroblastoma.
Copyright (C) 1998 by W.B. Saunders Company..
33. H Hattori, A Matsuzaki, A Suminoe, K Ihara, M Eguchi, T Tajiri, S Suita, E Ishii, T Hara, Genomic imprinting of insulin-like growth factor-2 in infant leukemia and childhood neuroblastoma, CANCER, 88, 10, 2372-2377, 2000.05, BACKGROUND. Loss of imprinting (LOI) of insulin-like growth factor-2 (IGF-2) has been implicated in the pathogenesis of certain human cancers and tumor-predisposing overgrowth disorders, such as Beckwith-Wiedemann syndrome. In a previous study, the authors revealed that certain patients with childhood acute leukemia and neuroblastoma had had rapid somatic growth after birth, suggesting the involvement of growth factor(s) in tumorigenesis. In the current study, the authors examined whether relaxation of IGF-2 imprinting occurred in infant leukemia and childhood neuroblastoma.
METHODS. The genomic DNA of infant leukemia, childhood neuroblastoma, and control individuals was amplified by polymerase chain reaction (PCR). Patients who had heterozygous genotype were selected as informative cases using Apa I polymorphism in exon 9 of the IGF-2 gene. Total RNA was isolated from informative cases, followed by cDNA synthesis. cDNA was amplified by PCR, and direct sequence was performed for determining allele specific transcription.
RESULTS. Twenty of 22 infant leukemia blasts and ail of 16 neuroblastoma cells showed normal monoallelic expression of IGF-2 as well as 23 controls. The height and weight of two acute lymphoblastic leukemia patients with LOI were within normal ranges for Japanese children.
CONCLUSIONS. The current study revealed that the imprinting status of IGF-2 was generally maintained in infant leukemia and confirmed that it was maintained in childhood neuroblastoma. The results suggest that LOI of IGF-2 does not play a major role in the carcinogenesis of these diseases or in rapid physical growth of the patients. Cancer 2000;88:2372-7. (C) 2000 American Cancer Society..
34. Y Kinoshita, S Tamiya, Y Oda, K Mimori, H Inoue, S Ohta, T Tajiri, S Suita, M Tsuneyoshi, Establishment and characterization of malignant rhabdoid tumor of the kidney, ONCOLOGY REPORTS, 8, 1, 43-48, 2001.01, Malignant rhabdoid tumor of the kidney (MRTK) is a highly aggressive tumor which occurs in childhood and which is histologically characterized by the existence of eosinophilic intracytoplasmic inclusions. We established and characterized a cell line from this tumor with histological, immunohistochemical and cytogenetical analysis. Histologically, the tumor cells demonstrate typical eosinophilic inclusions, while immunohistochemically the cells demonstrate common mesenchymal and epithelial differentiation. Although the conventional karyotyping of this tumor lacked the abnormalities of 22q chromosome, Southern blot analysis and microsatellite analysis verified abnormalities of the BCR gene and of the hSNF5/INI1 gene. Despite the variety of locations, these common genetic abnormalities appear to contribute to distinguish rhabdoid tumor from such other small round cell tumors as primitive neuroectodermal tumor, rhabdomyosarcoma, poorly differentiated synovial sarcoma and desmoplastic small round cell tumor..
35. S Tanaka, T Tajiri, S Noguchi, K Shono, K Ihara, T Hara, S Suita, Clinical significance of a highly sensitive analysis for gene dosage and the expression level of MYCN in neuroblastoma, JOURNAL OF PEDIATRIC SURGERY, 10.1016/S0022-3468(03)00707-3, 39, 1, 63-68, 2004.01, Background: The amplification of the MYCN gene is one of the most powerful adverse prognosis factors in neuroblastoma, but the clinical significance of an enhanced expression of MYCN remains controversial. To reassess the clinical implications of MYCN amplification and expression in neuroblastoma, the status of amplification and the expression level of the MYCN gene of primary neuroblastoma samples were analyzed using highly sensitive analyses.
Methods: Using a quantitative polymerase chain reaction (PCR) method (TaqMan), the gene dosages (MYCN/p53) of 66 primary neuroblastoma samples were determined. In all 66 samples, the status of MYCN amplification has been determined previously by the Southern blotting method. Of the 54 samples with a single copy of MYCN based on the Southern blotting method, 23 samples were analyzed for MYCN amplification using the fluorescence in situ hybridization (FISH) method. The expression levels (MYCN/GAPDH) of 56 samples were determined by a quantitative reverse transcriptase (RT)-PCR method.
Results: Of the 54 samples with a single copy of MYCN based on the Southern blotting method, 46 samples showed MYCN gene dosages of less than 2.0, whereas the remaining 8 samples with dosages of more than 2.0 were tumors from patients with advanced-stage disease. The results of FISH supported the fact that these 8 samples contained a small number of MYCN-amplified cells. The cases of MYCN gene dosages of more than 2.0 were significantly associated with all other unfavorable prognostic factors (an age of > 1 year at diagnosis [P < .0001], nonmass screening [P = .0003], advanced stage [P < .0001], diploid or tetraploid JP < .00011, and a Shimada unfavorable histology [P < .0001]). MYCN gene dosages of more than 2.0 were significantly associated with a high expression of MYCN (P = .0459). However, the expression level of MYCN was not significantly associated with any other prognostic factors.
Conclusions: Quantitative PCR may thus be a useful modality for performing a highly sensitive and accurate assessment of the amplification and expression levels of the MYCN gene. In particular, the combination of the quantitative PCR system and the FISH method is considered to be a highly effective method for evaluating the status of MYCN amplification. In this highly sensitive analysis, MYCN amplification (MYCN/p53 greater than or equal to 2.0) was reconfirmed to be a strongly unfavorable factor, whereas the expression level of MYCN does not appear to be an independently significant prognosis factor. (C) 2004 Elsevier Inc. All rights reserved..
36. T. Iehara, H. Hosoi, K. Akazawa, Y. Matsumoto, K. Yamamoto, S. Suita, T. Tajiri, T. Kusafuka, E. Hiyama, M. Kaneko, F. Sasaki, T. Sugimoto, T. Sawada, MYCN gene amplification is a powerful prognostic factor even in infantile neuroblastoma detected by mass screening, BRITISH JOURNAL OF CANCER, 10.1038/sj.bjc.6603149, 94, 10, 1510-1515, 2006.05, MYCN is the most powerful prognostic factor in cases of older children. However, how MYCN is related to the prognosis of infantile cases is not clear. A mass screening program was carried out by measuring urinary catecholamine metabolites (VMA and HVA) from 6-month-old infants. Of 2084 cases detected by the screening program, MYCN amplification (MNA) was examined by Southern blot analyses in 1533 cases from 1987 to 2000. Of the 1533 cases examined, 1500 (97.8%) showed no MNA, 20 cases (1.3%) showed MNA from three to nine copies, and 13 (0.8%) cases showed more than 10 copies. The 4-year overall survival rates of these three groups (99, 89 and 53%, respectively) were significantly different (P < 0.001), indicating that MYCN copy number correlates with the prognosis. Cases with MNA more than 10 copies were more advanced than those without amplification (stage III, IV vs I, II, IVs; P < 0.001). Patients with MNA more than 10 copies had significantly higher serum levels of neuron-specific-enolase (NSE) and ferritin than non-amplified patients (P = 0.049, P = 0.025, respectively). MYCN amplification was strongly correlated with a poor prognosis in infantile neuroblastoma cases. Therefore, for the selection of appropriate treatment, an accurate determination of MNA is indispensable..
37. Y Shima, T Tajiri, T Taguchi, S Suita, Increased expression of c-fos and c-jun in the rat small intestinal epithelium after ischemia-reperfusion injury: a possible correlation with the proliferation or apoptosis of intestinal epithelial cells, JOURNAL OF PEDIATRIC SURGERY, 10.1016/j.pedsurg.2005.12.025, 41, 4, 830-836, 2006.04, Background and Purpose: An increased expression of immediate early genes, such as the c-fos and c-Jun, is observed in some organs after ischemia-reperfusion (I/R) injury. These factors have been revealed to potentially induce apoptosis and proliferation of the postischemic cells. The purpose of this study is to analyze the relationship between the expression patterns of such immediate early genes and the cellular responses in the intestinal epithelial cells (JECs) after I/R stress.
Methods: The rat small intestine was reperfused after 30 minutes ischemia. Semiquantitative reverse transcription-polymerase chain reaction was used to quantify c-fos and c-jun messenger RNAs. The proliferation and apoptosis of IECs were detected by immunohistochemistry and the in situ terminal deoxynucleotidyl transferase-mediated dUTP biotin nick-end labeling method, respectively. fios and c-jun showed characteristic patterns in the IECs
Results: The messenger RNA levels of the after the I/R stress. The proliferation of the cells was initially observed after the I/R stress, followed by apoptosis of the cells.
Conclusions: The sequential expression patterns of these factors are possibly related to the proliferation and apoptosis of the IECs. (c) 2006 Elsevier Inc. All rights reserved..
38. T Tajiri, S Tanaka, M Higashi, Y Kinoshita, Y Takahashi, K Tatsuta, S Suita, Biological diagnosis for neuroblastoma using the combination of highly sensitive analysis of prognostic factors, JOURNAL OF PEDIATRIC SURGERY, 10.1016/j.jpedsurg.2005.11.067, 41, 3, 560-566, 2006.03, Background/Purpose: To select the optimal treatment according to the degree of malignancy of neuroblastoma, it is essential to accurately and rapidly identify any genetic abnormalities associated with the prognosis. This study aims to assess the correlation between the combination of prognostic factors and the biologic findings of neuroblastoma using a highly sensitive analysis of prognostic factors.
Methods: In 44 neuroblastoma primary samples, we determined the gene dosages of MYCN and Survivin (as the target of 17q gain) and the expression levels of MYCN, Survivin, and BINI using highly sensitive analysis (the quantitative polymerase chain reaction method); furthermore, we assessed the correlation between the combination of their prognostic factors and the biology of neuroblastoma.
Results: The gene dosage of MYCN or Survivin was significantly associated with all known prognostic factors. The expression level of MYCN or Survivin was not significantly associated with any prognostic factors, whereas the expression level of BINI was significantly associated with 5 of 6 prognostic factors. Regarding the combination of MYCN amplification and 17q gain (the gene dosage of Survivin), and the low expression of BINI, the rates of advanced stages (stage III or IV) were 100% for the cases with 3 factors, 63% for the cases with 2 factors, 42% for the cases with I factor, and 0% for the cases with null factor. Furthermore, the survival rates were 20% for the cases with 3 factors, 50% for the cases with 2 factors, 100% for the cases with 1 factor, and 100% for the cases with null factor.
Conclusion: The combination of gene dosages of MYCN and Survivin and the expression level of BINI using the quantitative polymerase chain reaction method was significantly correlated with the clinical stage and the patients' outcome. This combination of biologic factors may enhance the accuracy to the conventional criteria, but this would have to be shown in a much larger study that is adequately powered to detect such an advantage. (c) 2006 Elsevier Inc. All rights reserved..
39. M. Salem, Y. Kinoshita, T. Tajiri, R. Souzaki, K. Tatsuta, M. Higashi, T. Izaki, K. Kohashi, M. Tsuneyoshi, T. Taguchi, Association between the HER2 expression and histological differentiation in Wilms tumor, Pediatric Surgery International, 10.1007/s00383-006-1762-0, 22, 11, 891-896, 2006.11, Human epidermal growth factor receptors (HER) play a critical role in the branching morphogenesis of renal tubules. In the current study, we analyzed the expression of HER2 in Wilms tumor and assessed the role of this gene in the tumorgenesis of Wilms tumor. During the period from 1960 to 2005, 40 patients with Wilms tumor were treated in our department. Twenty-four of those patients (except those with clear cell sarcoma of the kidney and malignant rhabdoid tumor of the kidney) were collected and assessed. The histological component of each Wilms tumor was divided into three categories (epithelial, blastemal, and mesenchymal) and the extent of HER2 protein expression was analyzed immunohistochemically. The normal kidney tissue accompanied with 12 cases of Wilms tumor was also examined. In the normal kidney, HER2 showed a strong immunoreactivity in the cell membranes of the collecting tubules and in the endothelial cells. Of 24 cases, 15 cases showed an epithelial component, while 24 cases had a blastemal component and 21 cases had a mesenchymal component, respectively. Among the 15 specimens with epithelial cell differentiation, eight (53.3%) showed HER2 immunoreactive epithelial cells. HER2 immunoreactive blastemal cells were present in 11 (45.8%) of 24 specimens with blastemal cells. On the other hand, only 3 (14.3%) of 21 specimens containing mesenchymal cells showed HER2 immunoreactivity. These results suggest that the extent of HER2 expression is associated with epithelial differentiation in Wilms tumor. These histological findings may therefore help to explain the development of Wilms tumor from the standpoint of histological differentiation. © 2006 Springer-Verlag..
40. Eiso Hiyama, Toru Sugimoto, Yutaka Hayashi, Masahiko Fukuzawa, Fumiaki Sasaki, Masahiko Sugiyama, Satoshi Kondo, Akihiro Yoneda, Tatsuro Tajiri, Hiroaki Yamaoka, Lehara Tomoko, Kohei Akazawa, Megu Ohtaki, Screening at 6 months of age reduced neuroblastoma incidence and mortality at elder age: Population based cohort study in Japan, PEDIATRIC BLOOD & CANCER, 49, 4, 418-418, 2007.10.
41. Masataka Ishimura, Shouichi Ohga, Yoshihisa Nagatoshi, Jun Okamura, Tatsuro Tajiri, Kenichi Kohashi, Yoshinao Oda, Hidetoshi Takada, Toshiro Hara, Malignant hepatic tumor occurring 10 yrs after a histocompatible sibling donor bone marrow transplantation for severe aplastic anemia, PEDIATRIC TRANSPLANTATION, 10.1111/j.1399-3046.2007.00802.x, 11, 8, 945-949, 2007.12, A 13-yr-old boy developed post-transplant liver tumor. At three yrs of age, this patient underwent a histocompatible sibling donor BMT for severe aplastic anemia, after a conditioning with antithymocyte globulin and cyclophosphamide. He became a HBV carrier after BMT. Stable mixed chimerism and mild thrombocytopenia, but no active hepatitis continued. At age 13, abdominal pain was a sign of massive tumor. Extremely high levels of alpha-fetoprotein indicated the clinical diagnosis of hepatoblastoma that might be the first report as post-BMT malignancy. The necropsy specimens revealed that the tumor was recipient cell-origin and showed the histopathological features of both hepatoblastoma and hepatocellular carcinoma. Prolonged mixed chimerism and hepatitis virus infection might induce a rare oncogenesis after non-irradiated conditioning..
42. Sachiyo Suita, T. Tajiri, M. Higashi, S. Tanaka, Y. Kinoshita, Y. Takahashi, K. Tatsuta, Insights into infant neuroblastomas based on an analysis of neuroblastomas detected by mass screening at 6 months of age in Japan, European Journal of Pediatric Surgery, 10.1055/s-2006-924640, 17, 1, 23-28, 2007.02, Background/Purpose: Mass screening (MS) for neuroblastoma (NB) at 6 months of age in Japan was discontinued in 2004. We have previously reported that the majority of NB detected by MS showed a good prognosis, with only a few cases demonstrating an unfavorable outcome (J Pediatr Surg 2002, Cancer 2001). This study aims to provide insights into infant NB by assessing the details of the clinical courses in patients treated with a standard regimen and the biological features of such cases using highly sensitive methods at one institution in Japan. Methods: In 76 NB detected through MS treated at Kyushu University Hospital, the clinical features and MYCN amplification, 1p deletion, 17q gain, the expression level of TrkA using FISH and the quantitative PCR were analyzed. Results: Of these 76 persons with NB treated at one institution, 97% are still alive, while 2 cases died from other diseases. Three patients experienced a recurrence after complete remission (CR), and 2 patients demonstrated refractory disease since the initial diagnosis. Two of the 3 NB patients with recurrence have demonstrated a 2nd CR, while one case still has multiple active diseases. Regarding the findings of highly sensitive biological analyses, 5/74 (7%) showed MYCN amplification, 2/24 (8%) cases had a 1p deletion, 3/33 (9%) cases had a 17q gain, 5/50 (10%) cases had diploidy, 1/25 (4%) cases had a low expression of TrkA, and 2/76 (3%) cases had an unfavorable histology. Of the 76 NB, 13 tumors (17%) had one or more unfavorable factors (UF). Of the 5 refractory NB, 1 case had 3 UF, 1 case had 2 UF, 1 case had 1 UF, and 2 cases had no UF. As a result, 60% of the refractory NB had one or more UF. Conclusions: Of the NB detected by MS at one institution in Japan, 17% had one or more unfavorable factors (UF) and might have a higher risk of recurrence than the patients with no UF, although the unfavorable biology of several refractory cases is still unclear even after highly sensitive analyses. At least one-fifth of the NB cases detected by MS are anticipated cases. In infantile neuroblastomas, it may therefore be most important to analyze biologically prognostic factors using highly sensitive methods followed by immediate surgical intervention. Since the MS program has been discontinued in Japan, it will be necessary in future to assess the mortality and characteristics of NB detected clinically. © Georg Thieme Verlag KG Stuttgart. New York..
43. Suguru Fukahori, Hirohisa Yano, Makoto Tsuneoka, Yoshiaki Tanaka, Minoru Yagi, Michihiko Kuwano, Tatsuro Tajiri, Tomoaki Taguchi, Masazumi Tsuneyoshi, Masarnichi Kojiro, Immunohistochemical expressions of Cap43 and Mina53 proteins in neuroblastoma, JOURNAL OF PEDIATRIC SURGERY, 10.1016/j.jpedsurg.2007.07.008, 42, 11, 1831-1840, 2007.11, Background: We studied the expressions of both Mina53, which is a myc target gene and is related to cell proliferation, and Cap43, which is related to metastasis Suppression and downregulation of MYCN gene, in neuroblastoma.
Methods: Forty-eight surgically obtained neuroblastoma specimens were immunohistochemically stained. The Cap43 and Mina53 expression levels were determined, and their relationship to clinical prognostic factors, biological prognostic factors, and the patients' prognosis were examined.
Results: The Cap43 expression score was significantly high in the cases that had one of the good prognostic factors (<1 year old, early stage, mass screening case, no MYCN gene amplification), whereas the Mina53 expression score was high in those with poor prognostic factors. Regarding the MYCN expression site, the Cap43 expression score was significantly high in the cases demonstrating cytoplasm expression, whereas the Mina53 expression score was significantly high in the cases demonstrating nucleus expression. A significant relationship was found between Cap43 and TrkA, between Mina53 and Ki-67, and between Mina53 and TrkA. The prognosis was significantly favorable in the Cap43 high-expression cases, whereas it was significantly poor in the Mina53 high-expression cases.
Conclusions: Cap43 and Mina53 are both considered to be important biological and prognostic factors in neuroblastoma. (c) 2007 Elsevier Inc. All rights reserved..
44. Mayumi Higashi, Tatsuro Tajiri, Yoshiaki Kinoshita, Kyosuke Tatsuta, Ryota Souzaki, Yoshihiko Maehara, Sachiyo Suita, Tomoaki Taguchi, High expressions of neuronatin isoforms in favorable neuroblastoma, JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY, 29, 8, 551-556, 2007.08, Neuroblastoma is a malignant solid tumor of children, which derives from the embryonal sympathoadrenal linage. Clinical cases can vary widely from a favorable to an unfavorable prognosis according to the presence of genetic aberrations, such as MYCN amplification. Our cDNA microarray analysis which compared the gene expressions between favorable and unfavorable neuroblastomas showed a high expression of the neuronatin (Nnat) gene in favorable neuroblastomas. Nnat is highly conserved in mammalian species, and its expression appears in nervous systems from the hindbrain to the peripherals during the prenatal periods. The Nnat mRNA expression, investigated in 63 of neuroblastoma samples by quantitative reverse-transcription polymerase chain reaction, was found to be significantly higher in the favorable prognosis groups than in the unfavorable groups. Nnat is an imprinted gene, and its expression in IMR32 neuroblastoma cell line was up-regulated by treatment with a demethylating agent. High expressions of Nnat isoforms induced in an IMR32 neuroblastoma cell line changed the cell morphology to the extension of the neural processes, which thus indicated the occurrence of cell differentiation. In conclusion, the high expressions of Nnat were found to be associated with good prognoses in neuroblastoma, which might indicate tumor differentiation, and its suppressions in unfavorable tumors are considered to be under epigenetic control..
45. Eiso Hiyama, Hiroaki Yamaoka, Satoshi Kondo, Akihiro Yoneda, Tatsuro Tajiri, Masahiro Fukuzawa, Masahiko Sugiyama, Yutaka Hayashi, Fumiaki Sasaki, Megu Ohtaki, Heterogeneous subgroups in human neuroblastoma for clinically relevant risk stratification, PEDIATRIC SURGERY INTERNATIONAL, 10.1007/s00383-007-1998-3, 23, 11, 1051-1058, 2007.11, Neuroblastoma is a heterogeneous tumor and that may have a favorable or unfavorable prognosis. In Japan, a nation-wide neuroblastoma mass-screening (MS) project assessed 6-month-old infants between 1985 and 2003, and almost all neuroblastomas, including regressing or maturing tumors were thought to be detected in this period. To evaluate the heterogeneity of neuroblastoma subgroups, we analyzed patients with neuroblastoma who had been diagnosed during this period. The clinical courses of 4,209 patients with neuroblastoma, including 1,560 MS detected patients, whose tumors had been diagnosed between 1971 and 1995 were registered. The 2,520 cases registered between 1985 and 1995 were compared to 1,050 cases registered between 1971 and 1980 and analyzed by a multi-gene target model to determine the age distribution of neuroblastoma incidence. We hypothesized that three target genes were responsible for the progression of neuroblastoma: one pair of tumor suppressor gene alleles, one oncogene, and one gene controlling regression/differentiation. This simulation study revealed that the age distribution at initial diagnosis of neuroblastoma was divided into four groups based on post-fertilization age: 20-40, 40-50, 60-90, and 160-200 weeks. Since neuroblatoma in the first group occurred prenatal, post-natal clinical neuroblastoma can be classified into three age groups: 0-6 months, 1-2 years, and 3-4 years. The 0- to 6-month group consisted of mostly benign tumors, and the two older groups had predominantly malignant phenotypes. Our proposed model could explain qualitatively the distribution of neuroblastoma consisting of one subgroup with a favorable prognosis and two subgroups with unfavorable prognosis. For clinically relevant risk stratification, an age cutoff should be considered by the age distribution of these heterogeneous subgroups..
46. Tatsuro Tajiri, Mayumi Higashi, Ryota Souzaki, Kyousuke Tatsuta, Yoshiaki Kinoshita, Tomoaki Taguchi, Classification of neuroblastomas based on an analysis of the expression of genes related to prognosis, JOURNAL OF PEDIATRIC SURGERY, 10.1016/j.jpedsurg.2007.08.024, 42, 12, 2046-2049, 2007.12, Purpose: To select the optimal treatment according to the grade of malignancy of neuroblastoma (NB), it is essential to accurately and rapidly identify genetic abnormalities associated with the prognosis. We have identified BIN1 and neuronatin beta as the novel prognosis-related genes for NBs. This study aims to assess the correlation between the combination of the expression level of prognosis-related genes and the outcome of NB.
Methods: In 44 NB samples, the expression levels of TrkA, BIN], and neuronatin beta were determined using quantitative reverse transcriptase-polymerase chain reaction; furthermore, the correlation between the expression of these genes' expression levels and the clinical progression of NB were assessed.
Results: It was possible to classify 44 NBs into 4 groups regarding the grade of malignancy of NB. These 4 groups were all significantly associated with the clinical stages international NB staging system as well as the outcomes of the patients (P <.001, according to the trend test by Kruskal-Wallis exact test).
Conclusion: The combination of the expression levels of these genes using quantitative reverse transcriptase-polymerase chain reaction is indicated as the effective method to quickly and accurately evaluate the grade of malignancy of NBs. (c) 2007 Elsevier Inc. All rights reserved..
47. Y. Kinoshita, T. Tajiri, S. Ieiri, K. Nagata, T. Taguchi, S. Suita, K. Yamazaki, I. Yoshino, Y. Maehara, K. Kohashi, H. Yamamoto, Y. Oda, M. Tsuneyoshi, A case of an inflammatory myofibroblastic tumor in the lung which expressed TPM3-ALK gene fusion, PEDIATRIC SURGERY INTERNATIONAL, 10.1007/s00383-006-1821-6, 23, 6, 595-599, 2007.06, We herein describe a 4-year-old boy who after being treated for pneumonia showed an abnormal shadow at the hilus of the right lung on chest X-rays with continued inflammatory findings in his laboratory data. CT and MR investigations suggested the existence of a neoplasm at that site. An open biopsy was thus performed for a definite diagnosis. The histological findings and the expression of TPM3-ALK fusion gene confirmed a diagnosis of an inflammatory myofibroblastic tumor. A right upper and middle lobectomy including the tumor was thus performed for a complete resection. In addition to the histological diagnosis, the detection of the tumor specific fusion gene provided objective evidence in making a diagnosis..
48. 田尻 達郎, 田中 桜, 竜田 恭介, 米満 吉和, 上田 泰次, 田口 智章, 神経芽腫に対するセンダイウイルスベクターを用いた放射線併用樹状細胞免疫治療(Dendritic cell-based immunotherapy with local radiation using Sendai virus vector for neuroblastoma), 日本癌学会総会記事, 67回, 436-436, 2008.09.
49. Tatsuro Tajiri, Satoshi Ieiri, Yoshiaki Kinoshita, Kouji Masumoto, Yuko Nishimoto, Tomoaki Taguchi, Transumbilical approach for neonatal surgical diseases: woundless operation, PEDIATRIC SURGERY INTERNATIONAL, 10.1007/s00383-008-2230-9, 24, 10, 1123-1126, 2008.10, Purpose The transumbilical approach by means of a circumumbilical incision has up until recently been the main method for performing a pyloromyotomy. This study aims to assess the clinical usefulness of the transumbilical approach for neonates with a variety of surgical intraabdominal diseases in order to achieve minimally invasive surgery with excellent cosmetic results.
Methods In 14 neonates with surgical diseases (3 hypertrophic pyloric stenoses, 3 ileal atresias, 2 jejunal atresias, 1 duodenal stenosis, 1 duodenal atresia, 2 ovarian cysts, 1 malrotation, and 1 segmental dilatation of ileum), treatment using a transumbilical approach by means of a half circumumbilical incision was performed at our institution. The clinical features of 14 cases were evaluated.
Results Eight cases except for three patients with hypertrophic pyloric stenosis, two with ovarian cysts and one with intestinal malrotation underwent the operation within 4 days of birth. In 10 of 14 cases, the umbilicus was incised on its upper half circumference, while the umbilicus of 4 cases was incised on its lower half circumference. In one ileal atresia patient with a remarkable degree of oral intestinal dilatation, a slight additional transverse incision was added. In four cases (1 case with ileal atresia, 2 cases of an ovarian cyst, and 1 case with a segmental dilatation of the ileum), laparoscopy-assisted transumbilical surgery was performed. In all cases, no operative complications were encountered. Postoperatively, there was no wound in appearance and the umbilicus appeared to be normal.
Conclusion The transumbilical approach with or without laparoscopic assistance is considered to be a feasible, safe, and cosmetically excellent surgical procedure in neonates with a wide variety of surgical intraabdominal diseases..
50. Eiso Hiyama, Tomoko Iehara, Tohru Sugimoto, Masahiro Fukuzawa, Yutaka Hayashi, Fumiaki Sasaki, Masahiko Sugiyama, Satoshi Kondo, Akihiro Yoneda, Hiroaki Yamaoka, Tatsuro Tajiri, Kohei Akazawa, Mequ Ohtaki, Effectiveness of screening for neuroblastoma at 6 months of age: a retrospective population-based cohort study, LANCET, 10.1016/S0140-6736(08)60523-1, 371, 9619, 1173-1180, 2008.04, Background In Japan, a nationwide programme between 1984 and 2003 screened all infants for urinary catecholamine metabolites as a marker for neuroblastoma. Before 1989, this was done by qualitative spot tests for vanillylmandelic acid in urine, and subsequently by quantitative assay with high-performance liquid chromatography (HPLC). However, the Japanese government stopped the mass-screening programme in 2003, after reports that it did not reduce mortality due to neuroblastoma. We aimed to assess the effectiveness of the programme, by comparing the rates of incidence and mortality from neuroblastomas diagnosed before 6 years of age in three cohorts.
Methods We did a retrospective population-based cohort study on all children born between 1980 and 1998, except for a 2-year period from 1984. We divided these 22 289 695 children into three cohorts: children born before screening in 1980-83 (n=6 130 423); those born during qualitative screening in 1986-89 (n=5 290 412); and those born during quantitative screening 1990-98 (n=10 868 860). We used databases from hospitals, screening centres, and national cancer registries. Cases of neuroblastoma were followed up for a mean of 78.7 months.
Findings 21.56 cases of neuroblastorna per 100 000 births over 72 months were identified in the qualitatively screened group (relative risk [RR] 1 . 87, 95% Cl 1 . 66-2. 10), and 29.80 cases per 100 000 births over 72 months in the quantitatively screened group (RR 2.58, 2.33-2.86). The cumulative incidence of neuroblastorna in the prescreening cohort (11 . 56 cases per 100 000 births over 72 months) was lower than that in other cohorts (p<0 . 0001 for all comparisons), but more neuroblastomas were diagnosed after 24 months of age in this cohort (p=0 . 0002 for qualitative screening vs prescreening, p<0 . 0001 for quantitative screening vs prescreening). Cumulative mortality was lower in the qualititative screening (3.90 cases per 100 000 livebirths over 72 months) and quantitative screening cohorts (2.83 cases) than in the prescreening cohort (5.38 cases). Compared with the prescreening cohort, the relative risk of mortality was 0 . 73 (95% Cl 0 . 58-0.90) for qualitative screening, and 0 . 53 (0.42-0.63) for quantitative screening. Mortality rates for both the qualitative and quantitative screening groups were lower than were those for the prescreening cohort (p=0 . 0041 for prescreening vs qualitative screening, p<0. 0001 for prescreening vs quantitative screening).
Interpretation More infantile neuroblastomas were recorded in children who were screened for neuroblastoma at 6 months of age than in those who were not. The mortality rate from neuroblastoma in children who were screened at 6 months was lower than that in the prescreening cohort, especially in children screened by quantitative HPLC. Any new screening programme should aim to decrease mortality but also to minimise overdiagnosis of turnours with favourable prognoses (eg, by screening children at 18 months)..
51. Yoshinao Oda, Kenichi Kohashi, Hidetaka Yamamoto, Sadafumi Tamiya, Kimitoshi Kohno, Michihiko Kuwano, Yukihide Iwamoto, Tatsuro Tajiri, Tomoaki Taguchi, Masazumi Tsuneyoshi, Different expression profiles of Y-box-binding protein-1 and multidrug resistance-associated proteins between alveolar and embryonal rhabdomyosarcoma, CANCER SCIENCE, 10.1111/j.1349-7006.2008.00748.x, 99, 4, 726-732, 2008.04, Nuclear expression of the Y-box-binding protein-1 (YB-1) has been reported to regulate the expression of both P-glycoprotein (P-gp) and major vault protein (MVP), and to regulate proliferative activities in human malignancies. Based on morphology and molecular biology, rhabdomyosarcoma (RMS) can be divided into two major types: embryonal type and the more aggressive alveolar type. Thirty-five cases of embryonal RMS (ERMS) and 28 cases of alveolar RMS (ARMS) were examined immunohistochemically for the nuclear expression of YB-1 and the intrinsic expression of P-gp, multidrug resistance (MDR)-associated protein (MRP) 1, 2, and 3, breast-cancer resistant protein (BCRP) and MVP, and the findings were compared with proliferative activities as evaluated by the MIB-1-labeling index (LI). Moreover, mRNA levels of these MDR-related molecules were assessed using a quantitative reverse transcriptase-PCR method in 18 concordant frozen materials. P-gp expression was more frequently observed ARMS, compared with ERMS (P = 0.0332), whereas immunoreactivity for BCRP was more frequently recognized in ERMS (P = 0.0184). Nuclear expression of YB-1 protein was correlated with P-gp (P = 0.0359) and MVP (P = 0.0044) expression, and a higher MIB-1-labeling index (P = 0.0244) in ERMS, however, in ARMS no such relationships were observed. These immunohistochemical results indicate that different expression profiles of MDR-related molecules and their correlation with YB-1 nuclear expression support the concept that ERMS and ARMS are molecular biologically distinct neoplasms. Apart from ERMS, frequent P-gp expression in ARMS may be independent from YB-1 regulation. However, YB-1 may be a candidate for a molecular target in rhabdomyosarcoma therapy, especially in ERMS..
52. Yoshiaki Kinoshita, Tatsuro Tajiri, Ryota Souzaki, Kyousuke Tatsuta, Mayumi Higashi, Tomoko Izaki, Yukiko Takahashi, Tomoaki Taguchi, Diagnostic value of lectin reactive alpha-fetoprotein for neoinfantile hepatic tumors and malignant germ cell tumors - Preliminary study, JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY, 30, 6, 447-450, 2008.06, Background and Purpose: The serum alpha-fetoprotein (AFP) level has been used as a tumor marker for hepatoblastoma, and malignant germ cell tumors in pediatric patients. The AFP has 3 isoforms (L1, L2, L3), and the usefulness of the L3 fraction as a diagnostic marker for the adult hepatocellular carcinoma is well known. However, there are few reports dealing with various pediatric malignant tumors. In the current study, we analyzed the diagnostic value of AFP fractions for pediatric diseases, in particular, those occurring in the neoinfantile period.
Materials and Methods: From 2003 to 2006, two cases of hepatoblastoma, and 5 cases of germ cell tumor, all of which were neoinfantile, were treated in our department. In our analytical system (LiBASys), the level of the L3 fraction contains the majority of the L2 fraction. The total AFP (ng/mL) level and the L3 fraction (%) were measured to assess the usefulness of the L3 fraction as a diagnostic marker.
Results: In all cases of hepatoblastoma and yolk sac tumor, both the total AFP and the L3 fraction were high, either before treatment or in the presence of malignant tumors. Most of the cases of neonatal immature teratoma showed a high total AFP level during the neoinfantile period, however, the L3 fraction was around 10%, and decreased after surgical treatment. Only 1 case of the immature teratoma demonstrated malignant transformation, when the patient was 8 months old. As the total AFP and the AFP-L3 fraction were proportionally elevated, the patient was treated with additional surgical resection and chemotherapy. In the case of neonatal mature teratoma, the L3 fraction was below 0.5%, even when the total AFP level was high.
Discussion: Our results indicated that the level of the L3 fraction accurately confirmed the existence, or the malignant potential of hepatic tumor or germ cell tumor. The L3 fraction is useful as a tumor marker during the neoinfantile period..
53. Ryota Souzaki, Tatsuro Tajiri, Mayumi Higashi, Yoshiaki Kinoshita, Sakura Tanaka, Kenichi Kohashi, Masazumi Tsuneyoshi, Tomoaki Taguchi, Clinical implications of a slight increase in the gene dosage of MYCN in neuroblastoma determined using quantitative PCR, PEDIATRIC SURGERY INTERNATIONAL, 10.1007/s00383-008-2228-3, 24, 10, 1095-1100, 2008.10, Introduction Recently, determining the MYCN status in neuroblastoma (NB) using the quantitative PCR (Q-PCR) and FISH instead of the Southern blotting (SB) has been recommended. In order to assess the implications of the gene dosage of MYCN in NB, the MYCN status was evaluated using Q-PCR on DNA extracted from small areas of NB specimens obtained using laser capture microdissection (LCM).
Materials and methods MYCN gene dosages (MYCN/NAGK) were determined in 63 primary NB block samples, as well as in 243 microdissected tissues from 63 samples using Q-PCR. In 23 of 63 cases, the MYCN gene status was evaluated using FISH.
Results Nine block samples with the amplification of MYCN based on SB showed a remarkable increase of the MYCN gene dosage using Q-PCR. Twelve of 54 block samples with no amplification of MYCN based on SB showed a slight increase of the MYCN gene dosage (3.56 >= MYCN/NAGK > 1.84), and 8 of these 12 cases were in the advanced stage. Among these 12 cases, 1 case had several LCM areas with a high copy number of MYCN and several LCM areas which showed no increase of MYCN gene. Another case showed a slight increase in the MYCN gene dosage (3.65 <= MYCN/NAGK <= 4.82) in all LCM areas. In addition, a large number of cells with the MYCN gain were found using FISH in the block sample. In 2 other cases of 12 cases, although no LCM areas showed an increased gene dosage of MYCN, a small number of cells with MYCN amplification were found using FISH were found in the block sample.
Conclusion A slight increase in the gene dosage of MYCN detected by Q-PCR may indicate that the NB tissue contains a small number of cells with the MYCN amplification or a large number of cells with the MYCN gain, which are associated with the aggressive progression of NB..
54. Kouji Masumoto, Junko Akiyoshi, Kouji Nagata, Toru Uesugi, Shohei Taguchi, Tatsuro Tajiri, Tomoaki Taguchi, Chronological change in intramural components in severe proximally dilated jejunal atresia: An immunohistochemical study, JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION, 46, 5, 602-606, 2008.05.
55. Kenichi Kohashi, Yoshinao Oda, Hidetaka Yamamoto, Sadafumi Tamiya, Tomonari Takahira, Yukiko Takahashi, Tatsuro Tajiri, Tomoaki Taguchi, Sachiyo Suita, Masazumi Tsuneyoshi, Alterations of RB1 gene in embryonal and alveolar rhabdomyosarcoma: special reference to utility of pRB immunoreactivity in differential diagnosis of rhabdomyosarcoma subtype, JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY, 10.1007/s00432-008-0385-3, 134, 10, 1097-1103, 2008.10, Purpose Rhabdomyosarcoma (RMS), which is the most common pediatric soft tissue sarcoma, is classified into two major histologic subtypes, embryonal RMS (ERMS) and alveolar RMS (ARMS). RMS is occasionally reported to be the second neoplasm of hereditary retinoblastoma. Osteosarcoma is known as the most common second neoplasm of hereditary retinoblastoma, and tumorigenesis of osteosarcoma has been proven in previous studies to be related to the RB gene (RB1) alteration. Therefore, there might be a correlation between the tumorigenesis of RMS and RB1 alteration.
Methods We examined the RB protein (pRB) expression and RB1 alteration such as allelic imbalance (gain or loss) and homozygous deletion, using immunohistochemistry, microsatellite makers, and quantitative real-time PCR in 57 sporadic RMS.
Results Allelic imbalance was more frequently detected in ERMS (13/27), than in ARMS (3/20) (P = 0.04). Homozygous deletion on the protein-binding pocket domain of RB1 was found in 6 of 27 ERMS and in 2 of 20 ARMS (P = 0.24). Furthermore, immunohistochemical pRB labeling indexes (LI) in 31 ERMS (median value, 31%) were significantly reduced in comparison with those observed in 26 ARMS (median value, 85%) (P < 0.0001).
Conclusions Our results support the assertion that tumorigenesis of RMS may be associated with RB1 alteration especially in ERMS, as previously reported for osteosarcoma. As for the RB pathway, each subtype of RMS may have a different tumorigenesis. In addition, immunohistochemical pRB LI may have the potential to be a useful ancillary tool in the differential diagnosis of RMS subtypes..
56. Yukiko Takahashi, Yuko Nishimoto, Toshiharu Matsuura, Makoto Hayashida, Tatsuro Tajiri, Yuji Soejima, Akinobu Taketomi, Yoshihiko Maehara, Tomoaki Taguchi, Surgical complications after living donor liver transplantation in patients with biliary atresia: a relatively high incidence of portal vein complications, PEDIATRIC SURGERY INTERNATIONAL, 10.1007/s00383-009-2430-y, 25, 9, 745-751, 2009.09, The aim of this study is to present the surgical complications in living donor liver transplantation (LDLT) for biliary atresia (BA) as a treatment for end stage liver disease.
Twenty-nine LDLTs were performed in patients with BA between October 1996 and April 2008 in Department of Pediatric Surgery at Kyushu University Hospital. The initial immunosuppression was a combination of tacrolimus and steroids.
Twenty-eight of 29 cases with BA, who previously underwent Kasai's operation and LDLT was performed at a median age of 9.1 years (range 7 months to 28 years). Only one case was performed primary LDLT. Post-transplant complications included portal vein complications (n = 5), three of which successfully treated by Rex-shunt or ballooning. Others were bile leakage (n = 4), intestinal perforation (n = 4), and so on. The overall survival rate was 86.2% (25/29). One patient died of chronic rejection, surgical complications after LDLT in BA while others died of sepsis, multi-organ failure, and brain hemorrhage.
The incidence of portal vein complications and intestinal perforations was relatively high in LDLT for BA, possibly due to inflammation of the hepatoduodenal ligament and colonic adhesion to the liver. It is important to make an accurate diagnosis at an early stage and provide appropriate treatment..
57. Tatsuro Tajiri, Ryota Souzaki, Yoshiaki Kinoshita, Sakura Tanaka, Yuhki Koga, Aiko Suminoe, Akinobu Matsuzaki, Toshiro Hara, Tomoaki Taguchi, Risks and benefits of ending of mass screening for neuroblastoma at 6 months of age in Japan, JOURNAL OF PEDIATRIC SURGERY, 10.1016/j.jpedsurg.2009.07.050, 44, 12, 2253-2257, 2009.12, Purpose: The mass screening (MS) for neuroblastoma (NB) at 6 Months of age in Japan was discontinued in 2004. This study assessed the risks and benefits of MS based on an analysis of NB detected before or after discontinuation of MS in Japan.
Methods: The clinical features and Brodeur's genetic type based on MYCN, DNA ploidy, and other genetic aberrations were assessed in 113 NB patients (20 cases after and 93 cases [55 MS cases] before the discontinuation of MS) older than 6 months treated at one institution since 1985.
Results: The 20 patients with NBs detected after MS was discontinued ranged in age from 7 to 67 months, 12 patients were stage 4, and 11 patients would have been detected at 6 months of age if they had undergone MS. The Brodeur's genetic type of these 20 patients showed that 30% (6/20) were type 1 (low risk), 55% (11/20) were type 2A (intermediate risk), and 15% (3/20) were type 2B (high risk). Of 93 patients with NB detected before MS was discontinued, 60% (56/93) were type 1,18% (17/93) were type 2A, and 22% (20/93) were type 2B. Among the type 2A patients, 82% (9/11) of the patients detected after MS was discontinued showed stage 4, whereas only 50% (9/18) of those diagnosed before MS was discontinued were stage 4. The genetic analysis using single nucleotide polymorphism (SNP) array for type 2A showed that the pattern of genetic aberration was equivalent in those detected either before or after MS was discontinued.
Conclusions: There was a decrease of type 1 and an increase of type 2A NB in patients after MS was discontinued in Japan. These results suggest that most of the type 1 detected by MS has regressed, and most of the type 2A detected by MS has appeared sporadically as advanced NB in patients older than 1 year. (C) 2009 Elsevier Inc. All rights reserved..
58. Kenichi Kohashi, Yoshinao Oda, Mari Nakamori, Hidetaka Yamamoto, Sadafumi Tamiya, Taro Toubo, Yoshiaki Kinoshita, Tatsuro Tajiri, Tomoaki Taguchi, Masazumi Tsuneyoshi, Multifocal metanephric adenoma in childhood, PATHOLOGY INTERNATIONAL, 10.1111/j.1440-1827.2008.02324.x, 59, 1, 49-52, 2009.01, Metanephric adenoma is the most commonly occurring member of the metanephric tumor family, which also includes metanephric adenofibroma and metanephric stromal tumor. According to the World Health Organization classification, however, it is not commonly multifocal. Reported herein is the case of a 9-year-old boy with multifocal metanephric adenoma. Histologically, surgical sections showed multifocal proliferation of small rounded and uniform cells with smooth nuclear contours, scant pale-staining cytoplasm, dark-staining nuclei, and inconspicuous nucleoli: the cells were arranged in sheets and acinal, ductal, glomeruloid, and papillary structures. On immunohistochemistry the tumor cells were positive for vimentin, cytokeratins (CAM5.2, AE1/AE3, and CK18), and WT1, but negative for cytokeratin 7 (CK7) and epithelial membrane antigen (EMA). The Ki-67 labeling index was < 1%. In addition, cytogenetic analysis indicated a normal karyotype (46XY). Other histologically similar tumors are papillary renal cell carcinoma and nephroblastoma, and it is necessary to distinguish metanephric adenoma from those tumors because of malignancy. In contrast to those tumors, metanephric adenoma has inconspicuous nucleoli, loss of CK7 and EMA expression, and no mitotic figures. Thus, the histological and immunohistochemical features of the present case were compatible with metanephric adenoma..
59. Yuhki Koga, Akinobu Matsuzaki, Aiko Suminoe, Miho Hatano, Yusuke Saito, Yoshiaki Kinoshita, Tatsuro Tajiri, Tomoaki Taguchi, Kenichi Kohashi, Yoshinao Oda, Masazumi Tsuneyoshi, Toshiro Hara, Long-Term Survival After Autologous Peripheral Stem Cell Transplantation in Two Patients With Malignant Rhabdoid Tumor of the Kidney, PEDIATRIC BLOOD & CANCER, 10.1002/pbc.21958, 52, 7, 888-890, 2009.07, A 5-month-old male with stage It malignant rhabdoid tumor of the kidney (MRTK) and a 24-month-old male with stage III MRTK were treated with surgical resection of tumors and chemotherapy of alternating ICE (ifosfamide, carboplatin, and etoposide) and VDC (vincristine, doxorubicin, and cyclophosphamide), followed by high-dose chemotherapy using etoposide, carboplatin, and melphalan With autologous hematopoietic stem cell transplantation (SCT). Two patients have been alive without any evidence of disease for 30 and 37 months after diagnosis, respectively, and require no medication. Consolidation with SCT should be further studies for selected patients with high-risk MRTK. Pediatr Blood Cancer 2009;52:888-890. (C) 2009 Wiley-Liss, Inc..
60. Yoshiaki Kinoshita, Ryota Souzaki, Tatsuro Tajiri, Satoshi Ieiri, Makoto Hashizume, Tomoaki Taguchi, A preoperative evaluation for neo-infantile liver tumors using a three-dimensional reconstruction of multidetector row CT, ONCOLOGY REPORTS, 10.3892/or_00000298, 21, 4, 881-886, 2009.04, Multidetector row CT (MDCT), which has been used extensively in adult patients, has also recently been used for the evaluation of children. As pediatric surgeons, we pre-operatively examined 10 cases of liver tumors by MDCT and performed three-dimensional reconstruction and a volumetric analysis. Instead of angiography, which requires general anesthesia in children, this method can provide a fine image of the anatomy between the tumor and the vessels, as well as identify the presence of any anomalous vascular branches. It also makes it possible to calculate the residual liver volume for the proposed operation and to determine the optimal cut line. However, there are still certain problems associated with pediatric cases, including the determination of the appropriate volume of contrast medium, the occurrence of allergic reactions to the contrast medium, and the timing of enhancement. The resolution of the specific problems in the pediatric application of MDCT, and the development of a more effective procedure is thus required..
61. Yukiko Takahashi, Tatsuro Tajiri, Kouji Masumoto, Yoshiaki Kinoshita, Satoshi Ieiri, Toshiharu Matsuura, Mayumi Higashi, Tomoaki Taguchi, Umbilical crease incision for duodenal atresia achieves excellent cosmetic results, PEDIATRIC SURGERY INTERNATIONAL, 10.1007/s00383-010-2645-y, 26, 10, 963-966, 2010.10, The surgical procedure for treating congenital duodenal atresia has normally been performed by an upper abdominal transverse incision. Recently, duodenoduodenostomy has been attempted using an umbilical crease incision to improve the cosmetic results.
Eighteen cases of duodenal obstruction, including 15 atresia, 2 stenosis, and 1 atresia and stenosis, were treated from June 2001 to August 2009, in which 8 cases were performed via the umbilical crease incision and 10 cases via the conventional transverse incision. The clinical records of all cases were evaluated retrospectively.
All cases underwent radical operation safely. There were no differences in the operating time between the two kinds of incision. Two cases of umbilical crease incision showed minor complications. All the cases operated via the umbilical crease incision achieved a scarless abdomen within a few months after the operation.
The outcome of duodenal atresia is satisfactory with excellent cosmesis after a duodenoduodenostomy performed via the umbilical crease incision..
62. Ryota Souzaki, Tatsuro Tajiri, Yoshiaki Kinoshita, Sakura Tanaka, Yuhki Koga, Aiko Suminoe, Toshiro Hara, Kenichi Kohashi, Yoshinao Oda, Tomoaki Taguchi, Successful treatment of advanced pancreatoblastoma by a pylorus-preserving pancreatoduodenectomy after radiation and high-dose chemotherapy, PEDIATRIC SURGERY INTERNATIONAL, 10.1007/s00383-010-2655-9, 26, 10, 1045-1048, 2010.10, Pancreatoblastoma (PB) is a rare malignant pancreatic tumor in children and approximately 200 cases have been reported in the literature. The overall 5-year survival rate in PB is 43-50% and no standard treatment for PB has been established. This report presents the case of a 6-year-old female with advanced PB treated successfully by a pylorus-preserving pancreatoduodenectomy (PPPD) after induction chemotherapy, radiation and stem cell transplantation (SCT).
A 6-year-old girl was hospitalized for abdominal pain, fever, and vomiting. Abdominal computed tomography (CT) scan showed a 9-cm heterogeneous mass located at the pancreatic head and body, and the duodenum was completely compressed. The inferior vena cava, superior mesenteric artery, and vein were encased by the tumor. The tumor had well-defined margins and calcification. She showed severe anemia and her hemoglobin level was 4.0 g/dl, and the serum alpha-fetoprotein (AFP) level was elevated (884.8 ng/ml). Initially, a resection of the tumor was impossible. An open biopsy was performed and the histopathological diagnosis was PB. She underwent five cycles of the induction chemotherapy regimen for advanced neuroblastoma (cyclophosphamide, etoposide, vincristine, pirarubicin and cisplatin), and the tumor size was decreased to a diameter of 7.5 cm. Furthermore, chemotherapy with irinotecan and vincristine, radiotherapy (40 Gy) and SCT (etoposide, carboplatin, melphalan) was administered. The serum AFP level decreased to 41.1 ng/ml, and the tumor size was decreased to a diameter of 6.5 cm. Then she underwent a PPPD and the tumor was completely resected. The patient's recovery was uneventful, and the AFP returned to the normal values (6.2 ng/ml) after surgery. The child was administered mild postoperative chemotherapy using irinotecan and has been disease-free for 4 months and, and her serum AFP levels remain within normal values.
This is the first case of PB that was treated with SCT effectively before surgery. The combined therapy including the intensive chemotherapy with SCT and the radiation followed by surgical treatment is thought to be effective for the treatment of advanced PB..
63. Ryota Souzaki, Tatsuro Tajiri, Masae Souzaki, Yoshiaki Kinoshita, Sakura Tanaka, Kenichi Kohashi, Yoshinao Oda, Mitsuo Katano, Tomoaki Taguchi, Hedgehog signaling pathway in neuroblastoma differentiation, JOURNAL OF PEDIATRIC SURGERY, 10.1016/j.jpedsurg.2010.08.020, 45, 12, 2299-2304, 2010.12, Purpose: The hedgehog (Hh) signaling pathway is activated in some adult cancers. On the other hand, the Hh signaling pathway plays an important role in the development of the neural crest in embryos. The aim of this study is to show the activation of Hh signaling pathway in neuroblastoma (NB), a pediatric malignancy arising from neural crest cells, and to reveal the meaning of the Hh signaling pathway in NB development. Methods: This study analyzed the expression of Sonic hedgehog (Shh), GLI1, and Patched 1 (Ptch1), transactivators of Hh signaling pathway, by immunohistochemistry in 82 NB and 10 gang-lioneuroblastoma cases. All 92 cases were evaluated for the status of MYCN amplification. Results: Of the 92 cases, 67 (73%) were positive for Shh, 62 cases (67%) were positive for GLI1, and 73 cases (79%) were positive for Ptch1. Only 2 (10%) of the 20 cases with MYCN amplification were positive for Shh and GLI1, and 4 cases (20%) were positive for Ptch1 (MYCN amplification vs no MYCN amplification, P <=.01). The percentage of GLI1-positive cells in the cases with INSS stage 1 without MYCN amplification was significantly higher than that with INSS stage 4. Of 72 cases without MYCN amplification, 60 were GLI1-positive. Twelve cases were GLI1-negative, and the prognosis of the GLI1-positive cases was significantly better than that of the GLI1-negative cases (P =.015). Conclusions: Most of NBs without MYCN amplification were positive for Shh, GLI1, and Ptch1. In the cases without MYCN amplification, the high expression of GLI1 was significantly associated with early clinical stage and a good prognosis of the patients. In contrast to adult cancers, the activation of the Hh signaling pathway in NB may be associated with the differentiation of the NB. (C) 2010 Elsevier Inc. All rights reserved..
64. Tatsuro Tajiri, Ryota Souzaki, Yoshiaki Kinoshita, Sakura Tanaka, Yuhki Koga, Aiko Suminoe, Toshiro Hara, Kenichi Kohashi, Yoshinao Oda, Kouji Masumoto, Miki Ohira, Akira Nakagawara, Tomoaki Taguchi, Concordance for neuroblastoma in monozygotic twins: case report and review of the literature, JOURNAL OF PEDIATRIC SURGERY, 10.1016/j.jpedsurg.2010.08.025, 45, 12, 2312-2316, 2010.12, The patients were infant male twins born by cesarean delivery following a healthy pregnancy at 36 weeks' gestation to unrelated parents. At 4 months of age, twin 2 presented with hepatomegaly and a right suprarenal mass. Resection of an adrenal tumor and a liver tumor biopsy were performed. Twin 1 had no symptoms at 4 months of age. Screening by abdominal ultrasonography showed multiple masses in the liver but no adrenal mass. Metaiodobenzylguanidine scintigraphy showed positive findings in multiple liver masses. A laparoscopic biopsy for a liver tumor was performed. All primary tumor and liver tumor specimens from twin 2 and the liver tumor of twin 1 had the same histologic classification of neuroblastoma and nearly identical genetic aberrations, including a chromosome gain or loss using array-comparative genomic hybridization. From these clinical and pathologic findings and genetic analyses, we strongly demonstrate the transplacental metastatic spread from twin 2 to twin 1. In the literature, 9 pairs of concordant twin neuroblastomas, including the current twin, have been presented; and the clinical findings of 5 twin pairs may represent placental metastases from one twin with congenital neuroblastoma to the other twin. This study is the first report presenting the possibility of twin-to-twin metastasis in monozygotic twins with neuroblastoma based on an analysis of the clinical features and genetic aberrations. (C) 2010 Elsevier Inc. All rights reserved..
65. Ryota Souzaki, Tatsuro Tajiri, Risa Teshiba, Mayumi Higashi, Yoshiaki Kinoshita, Sakura Tanaka, Tomoaki Taguchi, The genetic and clinical significance of MYCN gain as detected by FISH in neuroblastoma, PEDIATRIC SURGERY INTERNATIONAL, 10.1007/s00383-010-2781-4, 27, 3, 231-236, 2011.03, MYCN amplification (MYCN-A) is a strong prognostic factor in neuroblastoma (NB). MYCN gain which is a low level of MYCN-A as determined by FISH. It is unclear whether the MYCN gain is the pre-status of MYCN-A. This study assessed the status of MYCN gene and chromosome 2p of MYCN-A, MYCN gain and no MYCN amplification using a single nucleotide polymorphism (SNP) array, and the clinical implication of MYCN gain in NB.
The status of the MYCN gene was determined by FISH in 47 primary NB samples and the status of chromosome 2p in all cases was analyzed using an SNP array.
8 of the 47 cases analyzed using FISH showed MYCN-A, 7 cases showed MYCN gain and 32 cases showed no MYCN amplification. An SNP array analysis showed that only 2 of 8 cases with MYCN-A by FISH had both amplification of MYCN region and distal 2p gain and other 6 cases had amplification of the MYCN region without distal 2p gain. All 7 cases with MYCN gain by FISH had distal 2p gain without amplification of the MYCN region, and all 32 cases with no MYCN amplification by FISH demonstrated neither the amplification of the MYCN region nor the 2p gain. 5-year overall survival rate of patients with MYCN gain (n = 7, 71.4%) was not significant different from that of patients with no MYCN amplification (n = 32, 90.6%) by FISH (p = 0.11).
These results suggested that the MYCN gain detected by FISH represents the 2p gain, and the MYCN gain is not considered to represent the pre-status of MYCN amplification..
66. Ryota Souzaki, Yoshiaki Kinoshita, Toshiharu Matsuura, Tatsuro Tajiri, Tomoaki Taguchi, Satoshi Ieiri, Jaesung Hong, Munenori Uemura, Kouzou Konishi, Morimasa Tomikawa, Kazuo Tanoue, Makoto Hashizume, Yuhki Koga, Aiko Suminoe, Toshiro Hara, Kenichi Kohashi, Yoshinao Oda, Successful resection of an undifferentiated sarcoma in a child using a real-time surgical navigation system in an open magnetic resonance imaging operation room, JOURNAL OF PEDIATRIC SURGERY, 10.1016/j.jpedsurg.2010.11.043, 46, 3, 608-611, 2011.03.
67. Tomoro Hishiki, Tadashi Matsunaga, Fumiaki Sasaki, Michihiro Yano, Kohmei Ida, Hiroshi Horie, Satoshi Kondo, Ken-Ichiro Watanabe, Takaharu Oue, Tatsuro Tajiri, Arata Kamimatsuse, Naomi Ohnuma, Eiso Hiyama, Outcome of hepatoblastomas treated using the Japanese Study Group for Pediatric Liver Tumor (JPLT) protocol-2: report from the JPLT, PEDIATRIC SURGERY INTERNATIONAL, 10.1007/s00383-010-2708-0, 27, 1, 1-8, 2011.01, Background In the recent years, surgical resection with pre-and/or postoperative chemotherapy has markedly improved the survival rate of hepatoblastoma patients. We herein report the results of patients treated with the current protocol of the Japanese Study Group for Pediatric Liver Tumor, JPLT-2.
Methods A total of 279 patients with malignant liver tumor were enrolled in JPLT-2. Data from 212 hepatoblastoma cases were analyzed. PRETEXT I patients were treated with primary resection followed by low doses of cisplatin-pirarubicin (tetrahydropyranyl-adriamycin). Otherwise, patients received preoperative cisplatin-pirarubicin (CITA), followed by surgery and postoperative chemotherapy. Ifosfamide, pirarubicin, etoposide, and carboplatin (ITEC) were given as a salvage treatment. High-dose chemotherapy with hematopoietic stem cell transplantation (SCT) was reserved for patients with metastatic diseases.
Results The 5-year overall survival rate (OS) in non-metastatic cases was 100% for PRETEXT I, 87.1% for PRETEXT II, 89.7% for PRETEXT III, and 78.3% for PRETEXT IV. The 5-year OS in metastatic cases was 43.9%. The outcome in non-metastatic PRETEXT IV cases was markedly improved, while the results of metastatic tumors remained poor.
Conclusions JPLT-2 protocol achieved satisfactory survival among children with non-metastatic hepatoblastoma. New approaches are needed for patients with metastatic diseases..
68. Risa Teshiba, Kouji Masumoto, Genshiro Esumi, Kouji Nagata, Yoshiaki Kinoshita, Tatsuro Tajiri, Tomoaki Taguchi, Ken Yamamoto, Identification of TCTE3 as a gene responsible for congenital diaphragmatic hernia using a high-resolution single-nucleotide polymorphism array, PEDIATRIC SURGERY INTERNATIONAL, 10.1007/s00383-010-2778-z, 27, 2, 193-198, 2011.02, Congenital diaphragmatic hernia (CDH) is a birth defect of the diaphragm associated with pulmonary hypoplasia. Although genetic factors have been suggested to play a role, the etiology of CDH is still largely unknown. In this study, we analyzed copy number variants (CNVs) using a single-nucleotide polymorphism (SNP) array to examine whether microdeletions contribute to the pathogenesis of this disease.
A total of 28 CDH patients, including 24 isolated and 4 non-isolated cases, were available. We performed CNV analysis using high-resolution SNP arrays (370K, 550K, 660K; Illumina Inc.) and CNstream software. Deletions in loci that have been suggested in previous studies to contain candidate genes affecting CDH were analyzed.
We detected 335, 6 and 133 deletions specific for patients in 14 (350K array), 3 (550K) and 11 (660K) cases, respectively. Among these deletions, no segments included the previously suggested candidate genes with the exception of an 18-kb deletion observed in the candidate locus 6q27 in two non-isolated patients. This deleted region contains exon 4 of the t-complex-associated-testis-expressed 3 (TCTE3) gene.
Because TCTE3 encodes a putative light chain of the outer dynein arm of cilia and human diseases caused by ciliary dysfunction show various phenotypes including skeletal defect, TCTE3 may be a genetic candidate influencing CDH..
69. Hayato Fujita, Kenoki Ohchida, Kazuhiro Mizumoto, Soichi Itaba, Tetsuhide Ito, Kohei Nakata, Jun Yu, Tadashi Kayashima, Akifumi Hayashi, Ryota Souzaki, Tatsuro Tajiri, Manabu Onimaru, Tatsuya Manabe, Takao OHTSuka, Masao Tanaka, High EGFR mRNA expression is a prognostic factor for reduced survival in pancreatic cancer after gemcitabine-based adjuvant chemotherapy, International Journal of Oncology, 10.3892/ijo.2011.908, 38, 3, 629-641, 2011.03, Pancreatic ductal adenocarcinoma (PDAC) still presents a major therapeutic challenge and a phase III clinical trial has revealed that the combination of gemcitabine and a human epidermal growth factor receptor type I (HER1/EGFR) targeting agent presented a significant benefit compared to treatment with gemcitabine alone. The aim of this study was to investigate EGFR mRNA expression in resected PDAC tissues and its correlation with patient prognosis. We obtained formalin-fixed paraffin-embedded (FFPE) tissue samples from 88 patients with PDAC who underwent pancreatectomy, and measured EGFR mRNA levels by quantitative real-time reverse transcription-polymerase chain reaction. The high-level EGFR group had significantly shorter disease-free-survival (p=0.029) and overall-survival (p=0.014) as shown by univariate analyses, although these did not reach statistical significance, as shown by multivariate analyses. However, we found that high EGFR expression was an independent prognostic factor in patients receiving gemcitabine-based adjuvant chemotherapy (p=0.023). Furthermore, we measured EGFR mRNA levels in 20 endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) cytological specimens. Altered EGFR levels were distinguishable in microdissected neoplastic cells from EUS-FNA cytological specimens compared to those in whole cell pellets. In conclusion, quantitative analysis of EGFR mRNA expression using FFPE tissue samples and microdissected neoplastic cells from EUS-FNA cytological specimens could be useful in predicting prognosis and sensitivity to gemcitabine in PDAC patients..
70. Chika Harada, Tomonobu Kawaguchi, Saiko Ogata-Suetsugu, Mizuho Yamada, Naoki Hamada, Takashige Maeyama, Ryota Souzaki, Tatsuro Tajiri, Tomoaki Taguchi, Kazuyoshi Kuwano, Yoichi Nakanishi, EGFR tyrosine kinase inhibition worsens acute lung injury in mice with repairing airway epithelium, American Journal of Respiratory and Critical Care Medicine, 10.1164/rccm.201002-0188OC, 183, 6, 743-751, 2011.03, Rationale: Epidermal growth factor receptor (EGFR) and its ligands play important roles in the regeneration of damaged epithelium and proliferation of various epithelial tumors. Although the EGFRtyrosine kinase inhibitor gefitinib is effective against advanced non - small cell lung cancer with EGFR mutations, some patients treated with this agent develop severe acute interstitial pneumonia. Characteristics of patients who develop interstitial pneumonia include older age, smoking history, and preexisting interstitial pneumonia suggesting a connection between airway injury and alveolar dysfunction. Objectives: The purpose of this study was to investigate the effects of gefitinib on airway repair after injury. Methods: C57BL/6J mice received intraperitoneally naphthalene at Day 0. Gefitinib (20, 90, or 200 mg/kg) was given daily at Days21 to 13 after naphthalene administration. Bronchoalveolar lavage fluid and lung tissue were obtained at Days 7 and 14. Terminal bronchial epithelial cells from Days 7 and 14 were retrieved with laser capture microdissection, and gene expression analyzed using microarray. Measurements and Main Results: Gefitinib treatment after naphthalene prolonged neutrophil sequestration and worsened acute lung injury. We found 17 genes with more than a threefold increase in bronchiolar epithelial cells from mice treated with 200 mg/kg of gefitinib after naphthalene at Day 14 compared with those treated with naphthalene alone. Up-regulated genes included S100A8, S100A6, and StefinA3. These genes are known to participate in neutrophil sequestration, acute inflammation, and airway remodeling. Conclusions: EGFR inhibition in repairing airway epithelial cells modulated significant expression of genes involved in the airway microenvironment, prolonged inflammation, and potentiated acute lung injury..
71. Ryota Souzaki, Tatsuro Tajiri, Risa Teshiba, Yoshiaki Kinoshita, Ryota Yosue, Kenichi Kohashi, Yoshinao Oda, Tomoaki Taguchi, Correlation between the number of segmental chromosome aberrations and the age at diagnosis of diploid neuroblastomas without MYCN amplification, JOURNAL OF PEDIATRIC SURGERY, 10.1016/j.jpedsurg.2011.09.005, 46, 12, 2228-2232, 2011.12, Background: In neuroblastomas (NBs) without MYCN amplification, segmental chromosome aberrations SCAs such as 1p loss, 11q loss, and 17q gain have been suggested to be associated with the prognosis of the patients. We assessed the correlation between the number of SCAs and other biological factors in primary NBs samples.
Method: The status of SCAs in 54 primary NBs samples was analyzed using the single-nucleotide polymorphism (SNP) array (Human CMV370-Duo; Illumina, San Diego, CA). The status of MYCN amplification was determined by an SNP array and the fluorescence in situ hybridization method. The DNA ploidy was determined by flow cytometry.
Results: Nine of 54 samples showed MYCN amplification. All 9 samples with MYCN amplification and 20 of 45 samples without MYCN amplification showed diploidy/tetraploidy, and the other 25 samples without MYCN amplification showed aneuploidy. The most frequent SCAs were 17q gain (26/54; 48.1%) and 11q loss (16/54; 29.6%), followed by 1p loss (15/54; 27.8%). The number of SCAs in diploidy/tetraploidy NBs without MYCN amplification (7.00 +/- 4.67) was higher than that in NBs with MYCN amplification (4.78 +/- 2.82) and in aneuploid NBs (1.64 +/- 2.78) (P < .05). In diploid/tetraploid NBs without MYCN amplification, there was a significant difference between an age at diagnosis less than 12 months (n = 7) and over 12 months (n = 13) (4.14 +/- 3.63 vs 8.54 +/- 4.54; P = .04). Moreover, the number of SCAs correlated with the age at diagnosis in diploid/tetraploid samples without MYCN amplification (r = 0.70, P = .0006). In NBs with MYCN amplification, the number of SCAs did not correlate with the age at diagnosis.
Conclusion: The number of SCAs significantly increased in proportion to age at diagnosis in diploid/tetraploid NBs without MYCN amplification. The increase in the number of these SCAs may play an important role in the prognosis of patients without MYCN amplification over 12 months of age. (C) 2011 Elsevier Inc. All rights reserved..
72. Tomoaki Taguchi, Kouji Nagata, Yoshiaki Kinoshita, Satoshi Ieiri, Tatsuro Tajiri, Risa Teshiba, Genshiro Esumi, Yuji Karashima, Sumio Hoka, Kouji Masumoto, The utility of muscle sparing axillar skin crease incision for pediatric thoracic surgery, PEDIATRIC SURGERY INTERNATIONAL, 10.1007/s00383-011-3013-2, 28, 3, 239-244, 2012.03, Posterolateral or standard axillar incisions for the pediatric thoracic surgery are occasionally associated with poor motor as well as cosmetic results, including chest deformities and large surgical scars. A muscle sparing axillar skin crease incision (MSASCI) was initially proposed by Bianchi et al. (in J Pediatr Surg 33:1798-1800, 1998) followed by Kalman and Verebely (in Eur J Pediatr Surg 12:226-229, 2002) resulting in satisfactory cosmetics. However, they performed operations through the third or fourth intercostals space (ICS), therefore the target organs were restricted in the upper two-thirds of the thoracic cavity.
Thoracic surgeries were performed using MSASCI in 27 patients (1-day to 9-year old). There were ten patients with esophageal atresia, seven with congenital cystic adenomatoid malformation, five with pulmonary sequestration, two with mediastinal neuroblastoma, two with right diaphragmatic hernia, and one with pulmonary hypertension. A thoracotomy was performed through the appropriate ICS (from third to eighth).
In all patients, the expected procedures, including pulmonary lower lobectomy, were successfully performed by MSASCI throughout the thoracic cavity. A good operational field was easily obtained in neonates and infants. Most of the patients achieved excellent motor and aesthetic outcomes.
MSASCI may become the standard approach for the thoracic surgery for small children..
73. Tatsuro Tajiri, Osamu Kimura, Shigehisa Fumino, Taizo Furukawa, Tomoko Iehara, Ryota Souzaki, Yoshiaki Kinoshita, Yuhki Koga, Aiko Suminoe, Toshiro Hara, Kenichi Kohashi, Yoshinao Oda, Tomoro Hishiki, Hajime Hosoi, Eiso Hiyama, Tomoaki Taguchi, Surgical strategies for unresectable hepatoblastomas, JOURNAL OF PEDIATRIC SURGERY, 10.1016/j.jpedsurg.2012.09.006, 47, 12, 2194-2198, 2012.12, Background: The aim of this study was to assess the surgical strategies for unresectable hepatoblastomas at the initial diagnosis based on the experience of two institutions.
Methods: The PRETEXT (Pretreatment evaluation of tumor extent) and POST-TEXT (Post treatment extent of disease) staging, surgical treatments, and clinical outcomes were retrospectively analyzed for 12 cases with PRETEXT III or IV and M(-) of 29 hepatoblastomas treated based on the JPLT-2 (The Japanese Study Group for Pediatric Liver Tumor-2) protocol at two institutions between 1998 and 2011.
Results: Two of the 9 cases with PRETEXT III status were downstaged to POST-TEXT II. One of the 3 cases with PRETEXT IV showed downstaging to POST-TEXT III. Four of the 7 cases with P2 or V3 (indicated for liver transplantation) in the PRETEXT staging system showed P2 or V3 in POST-TEXT staging after 2cycles of CITA (JPLT-2 standard regimen), and one case showed P2 or V3 in POST-TEXT staging at the initial operation and underwent primary liver transplantation. The initial surgical treatments were 1 lobectomy, 2 segmentectomies, 6 trisegmentectomies, 2 mesohepatectomies, and 1 primary liver transplantation. Both patients who underwent mesohepatectomies had bile leakage, and 1 of 5 trisegmentectomies had an acute obstruction of the right hepatic vein. Two patients underwent rescue living donor liver transplantation. Both of these patients showed P2 or V3 positive findings in POST-TEXT staging after 2 cycles of CITA.
Conclusions: POST-TEXT staging and P and V factors should be evaluated after 2cycles of CITA for unresectable hepatoblastomas detected at the initial diagnosis. The patients should be referred to the transplantation center if the POST-TEXT IV, P2, or V3 is positive at that time. Liver resection by trisegmentectomy is recommended in view of the incidence of surgical complications. Careful treatment, such as back-up transplantation, should thus be considered for liver resection in the cases with POST-TEXT IV, P2, or V3 status after initial 2cycles of CITA. (C) 2012 Elsevier Inc. All rights reserved..
74. Tatsuro Tajiri, Ryota Souzaki, Yoshiaki Kinoshita, Ryota Yosue, Kenichi Kohashi, Yoshinao Oda, Tomoaki Taguchi, Surgical intervention strategies for pediatric ovarian tumors: experience with 60 cases at one institution, PEDIATRIC SURGERY INTERNATIONAL, 10.1007/s00383-011-3004-3, 28, 1, 27-31, 2012.01, Purpose The aim of this study was to assess the surgical intervention strategies for pediatric ovarian tumors.
Methods The clinical features and treatment were analyzed for 60 children with ovarian tumors treated at our institution between 2000 and 2010.
Results Twenty-one of the 60 patients were prenatally diagnosed neonatal cases with cystic lesions. Of the 21 neonates, surgery included ultrasound-guided aspiration in 14 cases, salpingo-oophorectomy by umbilical crease incision in 6 cases with torsions, and cystectomy with ovarian preservation in one case with torsion. The mean age of the other 39 patients was 9.3 years. For 31 of these patients with benign lesions, surgery included tumor resection with ovarian preservation after aspiration of the cystic lesion through a modified Rocky Davis incision in 21 cases containing 3 torsion cases, and salpingo-oophorectomy in 10 cases, including 8 torsion cases. A salpingo-oophorectomy was performed for all eight of the patients with malignant tumors, including borderline lesions of mucinous or serous cyst adenoma, and postoperative chemotherapy was administered for two yolk sac tumors and one dysgerminoma. Only one case demonstrating a yolk sac tumor with lung metastasis at initial diagnosis died of disease after recurrence.
Conclusions The majority of pediatric ovarian tumors were benign disease, and the patients with malignant lesions had a good prognosis. In neonatal cases, an umbilical crease incision approach is feasible and provides excellent cosmesis. We recommend tumor resection with ovarian preservation through a minimally invasive approach (modified Rocky Davis incision) as the first line treatment for older pediatric patients with ovarian tumors other than those preoperatively diagnosed as malignant..
75. Tomoko Iehara, Eiso Hiyama, Tatsuro Tajiri, Akihiro Yoneda, Minoru Hamazaki, Masahiro Fukuzawa, Hajime Hosoi, Tohru Sugimoto, Tadashi Sawada, Is the prognosis of stage 4s neuroblastoma in patients 12 months of age and older really excellent?, EUROPEAN JOURNAL OF CANCER, 10.1016/j.ejca.2012.01.010, 48, 11, 1707-1712, 2012.07, Purpose: In the International Neuroblastoma Risk Group (INRG) classification system, stage 4s was changed into stage MS in children less than 18 months of age. Stage MS is defined as a metastatic disease with skin, liver and bone marrow, similar to INSS stage 4s. To evaluate the outcome of stage 4s cases in patients 12 months of age and over and to determine the appropriate treatment strategy.
Method: We performed a retrospective review of 3834 patients registered with the Japanese Society of Pediatric Oncology and Japanese Society of Pediatric Surgeons between 1980 and 1998.
Results: The rates of stage 4s patients were 10.7%, 6.3% and 3.3% in patients of <= 11 months of age, from >= 12 to <= 17 months of age, >= 18 months of age, respectively. The 5 year event-free survival rates were 89.4%, 100% and 53.1%, respectively. The rates of MYCN amplification and unfavourable histology were smaller in stage 4s groups than stage 4 groups in all ages.
Conclusion: In the children 12 months of age and older, stage 4s cases are markedly different from stage 4 cases in regard to the clinical features and prognosis. The prognosis of stage 4s cases from >= 12 to <= 17 months of age is excellent. The concept of stage MS appears to be appropriate. (C) 2012 Elsevier Ltd. All rights reserved..
76. Tatsuro Tajiri, Ryota Souzaki, Yoshiaki Kinoshita, Yuhki Koga, Aiko Suminoe, Toshiro Hara, Tomoaki Taguchi, Implications of surgical intervention in the treatment of neuroblastomas: 20-year experience of a single institution, SURGERY TODAY, 10.1007/s00595-011-0053-0, 42, 3, 220-224, 2012.02, The implications of surgical intervention for neuroblastomas were assessed in one institution.
We analyzed the clinical characteristics and extension of resection in 123 pediatric patients with neuroblastoma diagnosed between 1985 and 2004.
The 5-year survival rate of the 82 patients under 12 months of age, 59 of whom were treated with complete resection of the primary tumor, was 97%. The 5-year survival rate of the 41 patients over 12 months of age did not differ significantly according to whether complete (n = 19) or incomplete resection (n = 22) was performed (46 vs. 38%, respectively). No local recurrence was observed in ten patients over 12 months of age with stage 4 disease who underwent complete resection of the primary tumor; however, four of these ten patients died of metastatic recurrence.
Considering that the majority of infantile neuroblastomas in this study had favorable biology, complete resection might be unnecessary for patients under 12 years of age. For advanced neuroblastomas in patients over 12 months of age, the main treatment for metastasis is systemic chemotherapy, although extirpation of the primary tumor without extensive surgery might prevent local recurrence when combined with radiation therapy..
77. Review of Late-Presenting Congenital Diaphragmatic Hernia in Children
Purpose: Among patients with congenital diaphragmatic hernia (CDH), those with late-presenting CDH (LP-CDH) have been reported to have a better prognosis. However, it has also been reported that the diagnosis is not always easy, and delayed diagnosis may sometimes be life-threatening. This study reports on LP-CDH cases experienced in an institution for 23 years.
Methods: There were 10 LP-CDH cases (11.6%) between January 1987 and December 2010. They were retrospectively reviewed and investigated on the relationship with their ages at the LP-CDH onset, presenting symptoms, the period taken for diagnosis, contents of herniated organs, presence or absence of hernia sac and their outcome.
Results: The median age at diagnosis of LP-CDH was 1 year and 4 months (76 days to 15 years). Presenting symptoms were respiratory failure in 3, digestive symptom such as abdominal pain with vomiting in 6 cases. One case had no symptoms, and was found on routine chest X-ray examination at healthy check-up. The mean period from onset to diagnosis was 4.2 days. Hernia occurred in the gastrointestinal tracts in all cases, and none had liver herniation. Nine of 10 cases were rescued without any complications, although 1 case developed cardiopulmonary arrest on the way to our hospital and died without surgical intervention.
Conclusions: Unlike neonatal cases, LP-CDH cases often occur with digestive problems and diagnosis is often delayed. It should be noted that emergent chest X-ray and insertion of nasogastric tube to decompress stomach contents should be performed as soon as possible for their rescue when LP-CDH is suspected..
78. Tomoko Iehara, Minoru Hamazaki, Tatsuro Tajiri, Yoshifumi Kawano, Michio Kaneko, Hitoshi Ikeda, Hajime Hosoi, Tohru Sugimoto, Tadashi Sawada, Successful treatment of infants with localized neuroblastoma based on their MYCN status, International Journal of Clinical Oncology, 10.1007/s10147-012-0391-y, 18, 3, 389-395, 2013.06, Background: The aim of this study was to evaluate the effectiveness of post-surgical chemotherapy for infants with localized neuroblastoma without MYCN amplification (MNA), and determine whether risk classification using MNA is reasonable. Methods: Four hundred and fourteen eligible patients were registered between 1998 and 2004. Resectable patients in stage 1 and 2A/2B were treated by surgical resection only. Unresectable patients in stage 3 without MNA received either 6 cycles of regimen A or 3 cycles of regimen A plus 3 cycles of regimen C2
regimen A consisted of low doses of cyclophosphamide and vincristine and regimen C consisted of cyclophosphamide, vincristine and pirarubicin before surgical resection. The resectable and unresectable patients were randomly selected to receive post-surgical chemotherapy. The patients with MNA received intensive chemotherapy regimen D2, consisting of cyclophosphamide, vincristine, pirarubicin and cisplatin, and some of them received high-dose chemotherapy with stem cell transplantation. Results: The 5-year event-free survival (5-EFS) rates of stage 1 and 2A/2B patients without MNA were 97.2 and 89.0% respectively (p = 0.02). A total of 31 patients in stage 3 without MNA received post-surgical chemotherapy, and 30 patients did not. The 5-EFS rates of these two groups (96.0 and 96.2%, respectively) were not significantly different (p = 0.869). The 5-EFS rate for localized patients with MNA (n = 6) was 50.0%, and that of patients without MNA was 95.0% (p &lt
0.001). Conclusion: Post-surgical chemotherapy was therefore unnecessary for localized patients without MNA. This treatment strategy using MNA is considered to be appropriate in infants. © 2012 Japan Society of Clinical Oncology..
79. Osamu Kimura, Taizo Furukawa, Koji Higuchi, Yuuki Takeuchi, Shigehisa Fumino, Shigeyoshi Aoi, Tatsuro Tajiri, Impact of our new protocol on the outcome of the neonates with congenital diaphragmatic hernia, PEDIATRIC SURGERY INTERNATIONAL, 10.1007/s00383-012-3242-z, 29, 4, 335-339, 2013.04, Congenital diaphragmatic hernia (CDH) remains a defiant challenge for pediatric surgeons. Since 2003, we developed a new protocol aiming for the better outcome. In this study, the usefulness of our new protocol was evaluated.
Forty-six neonates with CDH at the age of less than 24 h were divided into two groups based on the difference of era and treatment protocols. In Group 1, 15 patients were treated between 1997 and 2002 and 31 patients were treated between 2003 and 2011 in Group 2. In the latter group, a new protocol was introduced focusing on the prevention of lung edema as well as lung injury by steroid administration and on the stabilization of cardiopulmonary function using continuous d-mannitol infusion. The survival rate and the postoperative intubation period (POIP) were compared between the two groups.
The overall survival rate was significantly increased from 53 % (8/15) to 81 % (25/31) (p < 0.05). In isolated CDH, the survival rate was increased from 58 to 93 %. The average POIP was remarkably shortened from 39.0 to 4.4 days (p < 0.01).
Our new protocol remarkably improved the survival rate and shortened the period of mechanical ventilation in neonates with CDH..
80. Kenichi Kohashi, Tetsuya Nakatsura, Yoshiaki Kinoshita, Hidetaka Yamamoto, Yuichi Yamada, Tatsuro Tajiri, Tomoaki Taguchi, Yukihide Iwamoto, Yoshinao Oda, Glypican 3 expression in tumors with loss of SMARCB1/INI1 protein expression, HUMAN PATHOLOGY, 10.1016/j.humpath.2012.06.014, 44, 4, 526-533, 2013.04, Glypican 3 (GPC3), a membrane-bound heparin sulfate proteoglycan, is mutated in Simpson-Golabi-Behmel syndrome, characterized by tissue overgrowth and an increased risk of embryonal malignancies such as Wilms tumor. Malignant rhabdoid tumor (MRT), originally described as a rhabdomyosarcomatoid variant of Wilms tumor, is a tumor with loss of SMARCB1/INI1 protein expression. We analyzed the frequency of GPC3 protein expression, GPC3 mRNA, and serum-soluble GPC3 levels in 71 cases of tumors with loss of SMARCB1/INI1 protein expression, including 14 MRTs, 48 epithelioid sarcomas (ES) (proximal-type, 21; distal-type, 27), 4 extraskeletal myxoid chondrosarcomas, and 5 pediatric undifferentiated soft-tissue sarcomas. We found that GPC3 overexpression of more than 10% of the labeling index was recognized in 6 (42.9%) MRTs, 1 (2.1%) proximal-type ES, and 3 (60%) pediatric undifferentiated soft-tissue sarcomas (MRT vs ES, P = .0003). All the remaining cases revealed GPC3-absent expression of less than 1% of the labeling index. The median values of GPC3 mRNA in the GPC3-absent expression group and overexpression group were 10.2 and 309, respectively, with a statistically significant difference between these 2 groups (P = .004). However, there was no statistically significant difference in the prognoses of these 2 groups of MRT (P = .99). In analyzable cases of small-number MRT and pediatric undifferentiated soft-tissue sarcoma, there is no significant correlation between GPC3 immunoreactivity and serum-soluble GPC3 level. Therefore, evaluation of GPC3 immunoexpression may be a useful diagnostic tool to distinguish ES from MRT, especially extrarenal MRT. It was suggested that MRTs with GPC3 overexpression may become a new target of GPC3 immunotherapy. (C) 2013 Elsevier Inc. All rights reserved..
81. Janette M. Rumbajan, Toshiyuki Maeda, Ryota Souzaki, Kazumasa Mitsui, Ken Higashimoto, Kazuhiko Nakabayashi, Hitomi Yatsuki, Kenichi Nishioka, Ryoko Harada, Shigehisa Aoki, Kenichi Kohashi, Yoshinao Oda, Kenichiro Hata, Tsutomu Saji, Tomoaki Taguchi, Tatsuro Tajiri, Hidenobu Soejima, Keiichiro Joh, Comprehensive analyses of imprinted differentially methylated regions reveal epigenetic and genetic characteristics in hepatoblastoma, BMC Cancer, 10.1186/1471-2407-13-608, 13, 2013.12, Background: Aberrant methylation at imprinted differentially methylated regions (DMRs) in human 11p15.5 has been reported in many tumors including hepatoblastoma. However, the methylation status of imprinted DMRs in imprinted loci scattered through the human genome has not been analyzed yet in any tumors.Methods: The methylation statuses of 33 imprinted DMRs were analyzed in 12 hepatoblastomas and adjacent normal liver tissue by MALDI-TOF MS and pyrosequencing. Uniparental disomy (UPD) and copy number abnormalities were investigated with DNA polymorphisms.Results: Among 33 DMRs analyzed, 18 showed aberrant methylation in at least 1 tumor. There was large deviation in the incidence of aberrant methylation among the DMRs. KvDMR1 and IGF2-DMR0 were the most frequently hypomethylated DMRs. INPP5Fv2-DMR and RB1-DMR were hypermethylated with high frequencies. Hypomethylation was observed at certain DMRs not only in tumors but also in a small number of adjacent histologically normal liver tissue, whereas hypermethylation was observed only in tumor samples. The methylation levels of long interspersed nuclear element-1 (LINE-1) did not show large differences between tumor tissue and normal liver controls. Chromosomal abnormalities were also found in some tumors. 11p15.5 and 20q13.3 loci showed the frequent occurrence of both genetic and epigenetic alterations.Conclusions: Our analyses revealed tumor-specific aberrant hypermethylation at some imprinted DMRs in 12 hepatoblastomas with additional suggestion for the possibility of hypomethylation prior to tumor development. Some loci showed both genetic and epigenetic alterations with high frequencies. These findings will aid in understanding the development of hepatoblastoma. © 2013 Rumbajan et al.
licensee BioMed Central Ltd..
82. Shigehisa Fumino, Koji Higuchi, Shigeyoshi Aoi, Taizo Furukawa, Osamu Kimura, Tatsuro Tajiri, Clinical analysis of liver fibrosis in choledochal cyst, PEDIATRIC SURGERY INTERNATIONAL, 10.1007/s00383-013-3368-7, 29, 11, 1097-1102, 2013.11, Although most patients with choledochal cyst (CC) have a favorable prognosis with prompt treatment, some of them are complicated with liver fibrosis, resulting in prolonged liver dysfunction even after definitive surgery. The aim of this study was to distinguish the high-risk group of liver fibrosis in patients with CC.
Fifteen patients who underwent liver biopsy during surgery for CC from 1981 to 2012 were enrolled in this study. Liver histology with H&E staining was graded according to Ohkuma's classification, and the correlation with the clinical characteristics was retrospectively assessed.
Their median age at biopsy was 13.4 months (range 1-42 months), and there were 7 in Ia, 2 in Ic, and 6 in IVa of the Todani classification. There were no significant differences in serum liver function test among those cyst types. The histological grades of liver fibrosis were as follows: grade 0 (no fibrosis) in 7 patients, grade 1 (mild) in 2, grade 2 (moderate) in 3, grade 3 (severe) in 2, grade 4 (cirrhosis) in 1. All 3 patients with grade 3 and 4 had CC with IVa and were under 18-month old. A 3-month-old girl with cirrhosis presented with severe jaundice resulting in living-donor liver transplantation despite bile drainage. A 16-month-old girl with grade 3 suffered from prolonged liver dysfunction and intractable ascites after surgery.
The progression of liver fibrosis is likely to be correlated with IVa, and the postoperative course might be unsatisfactory in advanced cases. The prompt surgical intervention is recommended especially for neonatal and infantile cases with type IVa cyst because irreversible liver cirrhosis could occur as early as in the infantile period..
83. Eiso Hiyama, Yuka Ueda, Yoshiyuki Onitake, Shou Kurihara, Kenichiro Watanabe, Tomoro Hishiki, Tatsuro Tajiri, Komei Ida, Michihiro Yano, Satoshi Kondo, Takaharu Oue, A cisplatin plus pirarubicin-based JPLT2 chemotherapy for hepatoblastoma: experience and future of the Japanese Study Group for Pediatric Liver Tumor (JPLT), PEDIATRIC SURGERY INTERNATIONAL, 10.1007/s00383-013-3399-0, 29, 10, 1071-1075, 2013.10, The Japanese Study Group for Pediatric Liver Tumor (JPLT) has conducted cooperative treatment studies on hepatoblastoma (HBL) since 1991. The JPLT2 protocol was launched in 1999 to evaluate the efficacy of cisplatin/pirarubicin (CITA) under risk stratification. European and North American groups showed the improvement of HBL patients by pre- and postoperative chemotherapeutic regimens. Therefore, we evaluated the results of JPLT study and considered the future aspect of JPLT.
A total of 389 children with malignant hepatic tumors were enrolled in JPLT-2 until 2010. Data from 331 HBL cases were analyzed.
Of the 331 patients enrolled, their 5-year overall survival and event-free survival rates were 83.3 and 68.0 %, respectively. While outcomes of standard-risk cases (tumors involving 3 or fewer sectors of the liver) were excellent, those of high-risk cases (tumors involving 4 sectors of the liver or with distant metastases) remained poor. For 26 high-risk or relapse/refractory HBL cases, high-dose chemotherapy (HDC) with stem cell transplantation (SCT) was carried out. Among them, 6 of 12 relapse or refractory cases died. Compared with other regimens, the CITA regimen achieved similar or superior rates of survival among children with standard-risk HBL, while HDC with SCT was not effective in patients with high-risk HBL. Presently, a global Children's Hepatic Tumor International Consortium (CHIC) project is ongoing, with a focus on international cooperation and risk stratification in the field of rare liver cancers in children. More promising strategies, including liver transplantation and new targeting drugs under global risk stratification, are being proposed..
84. Kohei Sakai, Osamu Kimura, Taizo Furukawa, Shigehisa Fumino, Koji Higuchi, Junko Wakao, Koseki Kimura, Shigeyoshi Aoi, Kouji Masumoto, Tatsuro Tajiri, Prenatal administration of neuropeptide bombesin promotes lung development in a rat model of nitrofen-induced congenital diaphragmatic hernia, JOURNAL OF PEDIATRIC SURGERY, 10.1016/j.jpedsurg.2014.09.015, 49, 12, 1749-1752, 2014.12, Background/purpose: Fetal medical treatment to improve lung hypoplasia in congenital diaphragmatic hernia (CDH) has yet to be established. The neuropeptide bombesin (BBS) might play an important role in lung development. The present study aims to determine whether prenatally administered BBS could be useful to promote fetal lung development in a rat model of nitrofen-induced CDH.
Methods: Pregnant rats were administered with nitrofen (100 mg) on gestation day 9.5 (E9.5). BBS (50 mg/kg/day) was then daily infused intraperitoneally from E14, and fetal lungs were harvested on E21. The expression of PCNA was assessed by both immunohistochemical staining and RT-PCR to determine the amount of cell proliferation. Lung maturity was assessed as the expression of TTF-1, a marker of alveolar epithelial cell type II.
Results: The lung-body-weight ratio was significantly increased in CDH/BBS(+) compared with CDH/BBS(-) (p < 0.05). The number of cells stained positive for PCNA and TTF-1 was significantly decreased in CDH/BBS (+) compared with CDH/BBS(-) (p < 0.01). The TTF-1 mRNA expression levels were significantly decreased in CDH/BBS(+) compared with CDH/BBS(-) (p < 0.05).
Conclusions: Prenatally administered BBS promotes lung development in a rat model of nitrofen-induced CDH. Neuropeptide BBS could help to rescue lung hypoplasia in fetal CDH. (C) 2014 Elsevier Inc. All rights reserved..
85. Shigehisa Fumino, Koseki Kimura, Tomoko Iehara, Motoki Nishimura, Satoaki Nakamura, Ryota Souzaki, Akihiro Nishie, Tomoaki Taguchi, Hajime Hosoi, Tatsuro Tajiri, Validity of image-defined risk factors in localized neuroblastoma: A report from two centers in Western Japan, JOURNAL OF PEDIATRIC SURGERY, 10.1016/j.jpedsurg.2015.08.039, 50, 12, 2102-2106, 2015.12, Background: Japanese Neuroblastoma Study Group (JNBSG) has been employing image-defined risk factors (IDRFs) since 2010. However, the report from INRG in 2011 supplemented description stating that isolated contact is considered to be IDRF-positive only in renal vessels. The aim of this study was to evaluate the validity of IDRFs by comparing the previous (PG) and new guidelines (NG).
Methods: IDRFs of patients with localized neuroblastoma treated at two centers in Western Japan from 2002 to 2013 were retrospectively reviewed by radiologists.
Results: 47 neuroblastomas (abdomen 38, pelvis 2, mediastinum 7) were evaluated. For abdominal neuroblastomas, IDRFs were present in 15/38 (39.5%) using PG and in 31/38 (81.6%) using NG. Moreover, the IDRF-positive rate increased from 26.7% (4/15) to 80.0% (12/15) in 15 cases diagnosed during mass screening. Of the IDRF-positive cases, complete primary resection was achieved in 2/15 (13.3%) using PG and 17/31 patients (54.8%) using NG. There were two major surgical renal complications in the IDRF-positive cases based on the use of either guidelines, and the specificity decreased from 64% to 19%.
Conclusions: According to NG, the IDRF-positive rate increased, and the resection rate decreased. NG may overestimate surgical risks, leading to unnecessary chemotherapy and a prolonged hospital stay. (c) 2015 Elsevier Inc. All rights reserved..
86. Taizo Furukawa, Osamu Kimura, Kouhei Sakai, Mayumi Higashi, Shigehisa Fumino, Shigeyoshi Aoi, Tatsuro Tajiri, Surgical intervention strategies for pediatric congenital cystic lesions of the lungs: A 20-year single-institution experience, JOURNAL OF PEDIATRIC SURGERY, 10.1016/j.jpedsurg.2015.08.019, 50, 12, 2025-2027, 2015.12, Background: The aim of this study was to assess surgical intervention strategies for congenital cystic lesions of the lungs (CCL), focusing on the safety of lung resection.
Materials and methods: The clinical features of 27 children (CCAM, n = 16; bronchial atresia, n = 4; bronchogenic cyst, n = 3; pulmonary sequestration, n = 3; lobar emphysema, n = 1) who were treated at our institution between 1995 and 2014 were analyzed.
Results: Of the 27 patients, 14 were asymptomatic, and 13 were symptomatic. The youngest symptomatic patient presented with pneumonia at 9 months of age. The mean age at surgery was 4 months in the asymptomatic group and 4.1 years in the symptomatic group. The mean operating time was 167 minutes in the asymptomatic group and 275 minutes in the symptomatic group (P < 0.001). The mean amount of intraoperative bleeding was 15 g in the asymptomatic group and 83.4 g in the symptomatic group (P < 0.05). All of the prenatally diagnosed patients underwent surgery within six months of birth. Three patients had remnant cystic lesions, all of which involved cystic lesions located over the lobulation anomalies of the lung.
Conclusions: To minimize surgical invasiveness, surgery for CCL should be performed during the asymptomatic period or within six months after birth. (c) 2015 Elsevier Inc. All rights reserved..
87. Successful laparoscopic extirpation of a large omental lipoblastoma in a child..
88. 経肛門的根治術を施行した直腸膜様閉鎖症の1例.
89. 先天性右横隔膜ヘルニア根治術後に肝捻転を生じた1例.
90. 【最近の漏斗胸・鳩胸の治療】 Nuss法術後出血に対する留意点.
91. 【小児疾患診療のための病態生理 3 改訂第5版】 血液・腫瘍性疾患 性腺腫瘍.
92. 【小児固形がんの最新のトピックス】 外科治療の役割と考え方.
93. 【小児固形がんの最新のトピックス】 神経芽腫のトピックス.
94. 【小児がん医療の現状と今後】 小児がん医療における小児外科医の役割.
95. 【先天性横隔膜ヘルニア最新の治療と今後の課題】 患児の術前術後の管理 鎮静の方法.
96. 【リンパ管奇形のすべて】 難治性リンパ管腫症に対するeverolimus(mTOR阻害剤)による治療経験.
97. 【シリーズ:こんなときどうする?(頭頸部・胸部編)】 術後難治性横隔膜ヘルニア門離解 再発防止のポイント.
98. 【この一冊でわかる甲状腺疾患】 小児の副甲状腺手術 異所性副甲状腺腫に対する術中intactPTH測定を併用したラジオナビゲーション手術.
99. Koseki Kimura, Tsunao Kishida, Junko Wakao, Tomoko Tanaka, Mayumi Higashi, Shigehisa Fumino, Shigeyoshi Aoi, Taizo Furukawa, Osam Mazda, Tatsuro Tajiri, Tumor-homing effect of human mesenchymal stem cells in a TH-MYCN mouse model of neuroblastoma, JOURNAL OF PEDIATRIC SURGERY, 10.1016/j.jpedsurg.2016.09.041, 51, 12, 2068-2073, 2016.12, Background: Human mesenchymal stem cells (hMSCs) are multipotent stem-like cells that are reported to have tumor-suppression effects and migration ability toward damaged tissues or tumors. The aim of this study was to analyze the tumor-homing ability of hMSCs and antitumor potency in a transgenic TH-MYCN mouse model of neuroblastoma (NB).
Methods: hMSCs (3 x 10(6)) labeled with DiR, a lipophilic near-infrared dye, were intraperitoneally (i.p.) or intravenously (i.v.) administered to the TH-MYCN mice. hMSC in vivo kinetics were assayed using the IVIS (R) imaging system for 24 h after injection. Immunohistochemistry using human CD90 antibody was also performed to confirm the location of hMSCs in various organs and tumors. Furthermore, the survival curve of TH-MYCN mice treated with hMSCs was compared to a control group administered PBS.
Results: i.p. hMSCs were recognized in the tumors of TH-MYCN mice by IVIS. hMSCs were also located inside the tumor tissue. Conversely, most of the i.v. hMSCs were captured by the lungs, and migration into the tumors was not noted. There was no significant difference in the survival between the hMSC and control groups.
Conclusion: The present study suggested that hMSCs may be potential tumor-specific therapeutic delivery vehicles in NB according to their homing potential to tumors. (C) 2016 Elsevier Inc. All rights reserved..
100. Shigehisa Fumino, Junnosuke Maniwa, Yuki Takeuchi, Kohei Sakai, Mayumi Higashi, Shigeyoshi Aoi, Taizo Furukawa, Osamu Kimura, Tatsuro Tajiri, Surgical intervention and perioperative risk factors of retroperitoneal teratomas in children: a single institution experience, PEDIATRIC SURGERY INTERNATIONAL, 10.1007/s00383-016-3938-6, 32, 9, 909-914, 2016.09, Retroperitoneal teratomas (RTs) are rare among germ cell tumors and predominantly occur in infants. RTs are often difficult to manage by perioperative management. In this study, we retrospectively reviewed our series of RTs.
Seventy patients with germ cell tumors were treated from 1989 to 2015 in our institution. Fourteen patients had RTs (3 boys and 11 girls). The median age at diagnosis was 5.5 months (range 0-64), and three were antenatally diagnosed.
All except one patient underwent total tumor excision. They exhibited dense adhesions with major vessels, and ligation of the splenic and gastroduodenal arteries was required in two patients. Injuries of PV and renal artery occurred in two patients. IVC injury in a neonate with a giant mass caused circulatory failure and brain death occurred postoperatively. Other major complications included injury of the diaphragm and bile duct. An infant whose tumor compressed the superior mesenteric artery developed enteritis while waiting for surgery and non-occlusive mesenteric ischemia, resulting in massive intestinal necrosis. The perioperative complication rate was 50 %.
Surgery for RTs remains challenging, and a preoperative evaluation of the vascular anatomy is crucial due to the high complication rate. Moreover, pre- and intraoperative fluid management is important to avoid any unexpected fatalities..
101. Tomoko Iehara, Shigeki Yagyu, Kunihiko Tsuchiya, Yasumichi Kuwahara, Mitsuru Miyachi, Tatsuro Tajiri, Tohru Sugimoto, Tadashi Sawada, Hajime Hosoi, Residual tumor in cases of intermediate-risk neuroblastoma did not influence the prognosis, JAPANESE JOURNAL OF CLINICAL ONCOLOGY, 10.1093/jjco/hyw050, 46, 7, 661-666, 2016.07, Background: It remains unclear whether a residual tumor mass following therapy influences the prognosis of neuroblastoma.
Methods: We retrospectively reviewed 20 patients with intermediate-risk tumors treated at our institution between 1993 and 2012 to elucidate whether additional treatment is required for residual tumors.
Results: The patient ages at diagnosis ranged from 0 days to 7 years. The 5-year overall survival rate was 94.4%. Thirteen patients had Stage 3 disease and seven patients had Stage 4 disease. Nine patients showed intraspinal extension. Twelve patients had a residual tumor mass at the completion of therapy, and eight showed intraspinal extension. Five of these 12 patients showed metaiodobenzylguanidine (MIBG) uptake at the end of treatment, but the uptake disappeared during the follow-up period. Except for one patient who died due to treatment complications, the rest are all alive, and nine are alive with a residual mass. We examined the residual mass in four patients and found that these tissues had differentiated into a ganglioneuroma or changed to a necrotic tissue. For the three patients with neurological symptoms at the end of treatment, some slight neurological symptoms still remained during the follow-up. Five patients with an intraspinal mass eventually presented with new symptoms.
Conclusions: The presence of a residual mass at the end of treatment did not influence the patients' prognosis. Therefore, an invasive radical surgical resection and additional treatment may not be necessary. Cases with a residual intraspinal mass also require a long-term follow-up to assess the neurological prognosis..
102. Tatsuro Tajiri, Neuroblastoma, Operative General Surgery in Neonates and Infants, 10.1007/978-4-431-55876-7_60, 365-370, 2016.06, Neuroblastoma is unique in its biological heterogeneity. As a result, it is crucial that the therapies selected for its treatment are appropriate according to the patient's classification based on several risk factors, including the patient's age, staging, and the grade of the tumor's biological malignancy. Surgery is one of the key options in the multidisciplinary therapies, with surgeries for neuroblastoma classified into three categories: Radical primary resection, open biopsy, and radical second-look operations. It is necessary to select the appropriate surgery on an individual basis. Recently, the Japan Neuroblastoma Study Group (JNBSG) has been performing clinical studies using a classification system that includes three risk groups (low, intermediate, and high) based on the risk classifications of the Children's Oncology Group (COG). The surgical guidelines combine the low and intermediate groups to create two groups of patients: The low- and intermediate-risk group and the high-risk group..
103. Tomoko Tanaka, Mayumi Higashi, Koseki Kimura, Junko Wakao, Shigehisa Fumino, Tomoko Iehara, Hajime Hosoi, Toshiyuki Sakai, Tatsuro Tajiri, MEK inhibitors as a novel therapy for neuroblastoma: Their in vitro effects and predicting their efficacy, JOURNAL OF PEDIATRIC SURGERY, 10.1016/j.jpedsurg.2016.09.043, 51, 12, 2074-2079, 2016.12, Background: A recent study reported that relapsed neuroblastomas had frequent RAS-ERK pathway mutations. We herein investigated the effects and pathways of MEK inhibitors, which inhibit the RAS-ERK pathway, as a new molecular-targeted therapy for refractory neuroblastomas.
Method: Five neuroblastoma cell lines were treated with trametinib (MEK inhibitor) or CH5126766 (RAF/MEK inhibitor). Growth inhibition was analyzed using a cell viability assay. ERK phosphorylation and the MYCN expression were analyzed by immunoblotting or immunohistochemistry. RAS/RAF mutations were identified by direct sequencing or through the COSMIC database.
Results: Both MEK inhibitors showed growth inhibition effects on cells with ERK phosphorylation, but almost no effect on cells without. In immunoblotting analyses, ERK phosphorylation and MYCN expression were suppressed in ERK active cells by these drugs. Furthermore, phosphorylated-ERK immunohistochemistry corresponded to the drug responses. Regarding the relationship between RAS/Raf mutations and ERK phosphorylation, ERK was phosphorylated in one cell line (NLF) without RAS/Raf mutations.
Conclusion: MEK inhibitors are a promising molecular-targeted therapeutic option for ERK active neuroblastomas. The efficacy of MEK inhibitors corresponds to ERK phosphorylation, while RAS/RAF mutations are not always detected in drug-sensitive cells. Phosphorylated-ERK immunohistochemistry is thus a useful method to analyze ERK activity and predict the therapeutic effects of MEK inhibitors. (C) 2016 Elsevier Inc. All rights reserved..
104. 術前MRCPにて画像診断し得た重複胆管を伴った膵・胆管合流異常の1例.
105. 腹腔鏡下大腸全摘術を施行した14歳colitic cancerの1例
The case of a 14-year-old girl who developed ulcerative colitis (UC) at 6 years of age and visited our hospital for treatment is presented. She was diagnosed with well-differentiated adenocarcinoma during lower gastrointestinal tract endoscopy as a follow-up evaluation. The patient then underwent laparoscopic total colectomy, D3 dissection, ileal pouch-anal anastomosis, and ileostomy. UC often occurs concurrently with colon cancer, and the frequency of colon cancer in UC patients is reportedly 1.8% within 10 years, 8.3% within 20 years, and 18.4% within 30 years of developing UC. In our institution, we have performed laparoscopic total colectomy for UC since 2007. Laparoscopic surgery may be a viable treatment option for the removal of colitic cancer in UC patients..
106. 学童期に短腸症候群となり、その後腸管延長術(STEP)により腸管吸収が改善した1例.
107. 女児低位鎖肛におけるcut back手術後の再手術症例の検討.
108. 回腸捻転を伴う続発性双極性大網捻転の1例.
109. 【小児科ケースカンファレンス】 血液、腫瘍 固形腫瘍(神経芽腫).
110. 【小児外科領域の先端的医療の展開(I):再生医療の最前線】 横隔膜の再生治療.
111. 【小児外来必携 お子さまの病気を専門医がわかりやすく説明します(II)】 鼠径ヘルニア 生後2ヵ月のとき、鼠径ヘルニアの診断で、1歳になったら手術といわれていたのですが、その後ふくれなくなりました.
112. Maho Inoue, Shigeyoshi Aoi, Akihiro Taniguchi, Kohei Sakai, Mayumi Higashi, Shigehisa Fumino, Taizo Furukawa, Tatsuro Tajiri, Laparoscopic intraperitoneal onlay mesh for pediatric incisional hernia-a case report., Surgical case reports, 10.1186/s40792-017-0400-5, 3, 1, 122-122, 2017.12, BACKGROUND: The incidence of incisional hernia in pediatric patients is low in comparison with that reported in adults. In the pediatric population, primary closure has generally been favored. However, synthetic or biomedical mesh offers advantages in the repair of larger defects when primary closure is difficult. The use of laparoscopic intraperitoneal onlay mesh (IPOM) in the adult population has been well documented. In the pediatric population, a few laparoscopic approaches with direct suturing have been proposed; however, there are no reports of laparoscopic repair with the use of IPOM. CASE PRESENTATION: The patient was a 1-year-old girl with epigastric incisional hernia after an operation to correct a complete arteriovenous septal defect. The fascial defect (size 30 × 35 mm) was large; thus, direct suturing was considered to be associated with a high risk of thoracic deformation and recurrence. Laparoscopic IPOM was performed. The fascial defect was detected precisely through the laparoscopy, and non-absorbable mesh was placed through a 12-mm trocar. Minimal incisions were required for the trocars, and extensive dissection of the abdominal wall structure was not needed. This procedure allowed for the integrity and functional status of the abdominal wall to be maintained. CONCLUSION: Laparoscopic IPOM is a minimally invasive and cosmetically acceptable method that can be applied to the treatment of large incisional hernias in children..
113. Kumiko Uryu, Riki Nishimura, Keisuke Kataoka, Yusuke Sato, Atsuko Nakazawa, Hiromichi Suzuki, Kenichi Yoshida, Masafumi Seki, Mitsuteru Hiwatari, Tomoya Isobe, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Satoru Miyano, Katsuyoshi Koh, Ryoji Hanada, Akira Oka, Yasuhide Hayashi, Miki Ohira, Takehiko Kamijo, Hiroki Nagase, Tetsuya Takimoto, Tatsuro Tajiri, Akira Nakagawara, Seishi Ogawa, Junko Takita, Identification of the genetic and clinical characteristics of neuroblastomas using genome-wide analysis., Oncotarget, 10.18632/oncotarget.22495, 8, 64, 107513-107529, 2017.12, To provide better insight into the genetic signatures of neuroblastomas, we analyzed 500 neuroblastomas (included specimens from JNBSG) using targeted-deep sequencing for 10 neuroblastoma-related genes and SNP arrays analysis. ALK expression was evaluated using immunohistochemical analysis in 259 samples. Based on genetic alterations, the following 6 subgroups were identified: groups A (ALK abnormalities), B (other gene mutations), C (MYCN amplification), D (11q loss of heterozygosity [LOH]), E (at least 1 copy number variants), and F (no genetic changes). Groups A to D showed advanced disease and poor prognosis, whereas groups E and F showed excellent prognosis. Intriguingly, in group A, MYCN amplification was not a significant prognostic marker, while high ALK expression was a relevant indicator for prognosis (P = 0.033). Notably, the co-existence of MYCN amplification and 1p LOH, and the co-deletion of 3p and 11q were significant predictors of relapse (P = 0.043 and P = 0.040). Additionally, 6q/8p LOH and 17q gain were promising indicators of survival in patients older than 5 years, and 1p, 4p, and 11q LOH potentially contributed to outcome prediction in the intermediate-risk group. Our genetic overview clarifies the clinical impact of genetic signatures and aids in the better understanding of genetic basis of neuroblastoma..
114. Yuanyuan Li, Miki Ohira, Yong Zhou, Teng Xiong, Wen Luo, Chao Yang, Xiangchun Li, Zhibo Gao, Rui Zhou, Yohko Nakamura, Takehiko Kamijo, Yasuhiko Kaneko, Takeshi Taketani, Junichi Ueyama, Tatsuro Tajiri, Hongyan Zhang, Jian Wang, Huanming Yang, Ye Yin, Akira Nakagawara, Genomic analysis-integrated whole-exome sequencing of neuroblastomas identifies genetic mutations in axon guidance pathway, ONCOTARGET, 10.18632/oncotarget.18079, 8, 34, 56684-56697, 2017.08, Neuroblastoma (NB) is a childhood solid malignant tumor originating from precursor cells of the peripheral nervous system. We have previously established a risk classification system based on DNA copy number profiles. To further explore the pathogenesis of NBs in distinct risk groups, we performed whole-exome sequencing analysis of 57 primary and 7 recurrent/metastatic tumors with unique chromosomal aberration profiles as categorized by our genomic sub-grouping system. Overall, a low frequency of somatic mutations was found. Besides ALK (4/64, 6.3%), SEMA6C, SLIT1 and NRAS, genes involved in the axon guidance pathway, were identified as recurrently mutated in 6 of 64 tumors (9.4%). Pathway enrichment analysis revealed enrichment of 25 mutated genes in the mitogen-activated protein kinase (MAPK) pathway, 13 genes in the Wnt pathway, and 12 genes in the axon guidance pathway. Genomic analyses demonstrated that primary and matched recurrent or metastatic tumors obtained from sporadic and monozygotic twin NBs were clonally related with variable extents of genetic heterogeneity. Monozygotic twin NBs displayed different evolutionary trajectories. These results indicate the involvement of the axon guidance, MAPK and Wnt pathways in NB and demonstrate genomic diversity with NB progression..
115. Junko Wakao, Tsunao Kishida, Shigehisa Fumino, Koseki Kimura, Kenta Yamamoto, Shin-ichiro Kotani, Katsura Mizushima, Yuji Naito, Toshikazu Yoshikawa, Tatsuro Tajiri, Osam Mazda, Efficient direct conversion of human fibroblasts into myogenic lineage induced by co-transduction with MYCL and MYOD1, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 10.1016/j.bbrc.2017.05.059, 488, 2, 368-373, 2017.06, The skeletal muscle consists of contractile myofibers and plays essential roles for maintenance of body posture, movement, and metabolic regulation. During the development and regeneration of the skeletal muscle tissue, the myoblasts fuse into multinucleated myotubes that subsequently form myofibers. Transplantation of myoblasts may make possible a novel regenerative therapy against defects or dysfunction of the skeletal muscle. It is reported that rodent fibroblasts are converted into myoblast-like cells and fuse to form syncytium after forced expression of exogenous myogenic differentiation 1 (MYOD1) that is a key transcription factor for myoblast differentiation. But human fibroblasts are less efficiently converted into myoblasts and rarely fused by MYOD1 alone. Here we found that transduction of v-myc avian myelocytomatosis viral oncogene lung carcinoma derived homolog (MYCL) gene in combination with MYOD1 gene induced myoblast-like phenotypes in human fibroblasts more strongly than MYOD1 gene alone. The rate of conversion was approximately 90%. The directly converted myoblasts (dMBs) underwent fusion in an ERK5 pathway-dependent manner. The dMBs also formed myofiber-like structure in vivo after an inoculation into mice at the subcutaneous tissue. The present results strongly suggest that the combination of MYCL plus MYOD1 may promote direct conversion of human fibroblasts into functional myoblasts that could potentially be used for regenerative therapy for muscle diseases and congenital muscle defects. (C) 2017 Elsevier Inc. All rights reserved..
116. Shigehisa Fumino, Kohei Sakai, Mayumi Higashi, Shigeyoshi Aoi, Taizo Furukawa, Masaaki Yamagishi, Masayoshi Inoue, Tomoko Iehara, Hajime Hosoi, Tatsuro Tajiri, Advanced surgical strategy for giant mediastinal germ cell tumor in children, Journal of Pediatric Surgery Case Reports, 10.1016/j.epsc.2017.09.023, 27, 51-55, 2017.12, Purpose Giant mediastinal germ cell tumor (MGCT) requires a well-planned advanced surgical approach. We retrospectively reviewed our surgical strategy for giant MGCT. Methods Five children (median age, 5 years) with giant MGCT were treated in our institute from 2012 to 2016. Results The initial diagnosis was made by tumor markers and image inspection in all cases. Benign teratomas (2 girls) and malignancies (3 boys) were treated with upfront surgery and radical tumorectomy after neo-adjuvant chemotherapy, respectively. After detailed 3D-CT, radical tumor excision was performed supported by a skilled pediatric cardiovascular surgeon. The basic approach was as follows: under cardiopulmonary support (CPS) or with CPS on standby, via median sternotomy, the pericardium and phrenic nerve were resected en bloc with the tumor, followed by diaphragmatic plication. Open biopsy was performed via lateral thoracotomy in 1 patient who showed dense adhesion and fistula formation in the lung
lobectomy via hemi-clamshell incision was required. No deaths or severe sequelae occurred in this series. Conclusions Resectability is the most important predictor of outcomes for MGCTs. Preoperative 3D-CT and CPS can enable complete resection and ensure surgical safety. Well-functioned surgical team is critical success factor in such advanced surgery..
117. 骨盤内病変を有する仙尾部奇形腫に対する低侵襲手術.
118. 術前3D-CTが有用であった乳児巨大後腹膜奇形腫の一摘除例.
119. 膵芽腫の一例.
120. 腹腔内全体を占拠する巨大大網嚢腫に対し単孔式腹腔鏡手術で全摘し得た1幼児例.
121. 胎児・新生児期診断された先天性胆道拡張症の外科治療の注意点.
122. 縦隔悪性腫瘍術後乳び胸に対して胸腔鏡下ポリグリコール酸シート併用組織接着剤被覆が有効であった1幼児例.
123. 神経芽腫に対する内視鏡外科手術の適応基準の作成と標準化へ向けた挑戦 全国調査からみた現状と集約化および臨床試験へ向けた可能性.
124. 成人重症心身障害者に発症した褥瘡を小児病棟管理で改善しえた1例.
125. 先天性横隔膜ヘルニアの低形成肺における気管支軟骨の組織計測学的解析.
126. サブスペシャル領域を見据えた新専門医制度のあり方 小児外科からみた新専門医制度のあり方 日本小児外科学会の取り組み.
127. 【「内視鏡外科手術の最前線」】 小児外科における内視鏡手術Up-to-Date.
128. Akari Takai, Tomoko Iehara, Mitsuru Miyachi, Yoshiki Okumura, Tatsuji Hasegawa, Sachiko Tokuda, Kazuyuki Ikeda, Masaaki Yamagishi, Tatsuro Tajiri, Hajime Hosoi, Successful treatment of a hepatic-hemangioendothelioma infant presenting with hypothyroidism and tetralogy of Fallot, Pediatrics and Neonatology, 10.1016/j.pedneo.2017.08.002, 59, 2, 216-218, 2018.04.
129. Kawakubo N, Tanaka S, Kinoshita Y, Tajiri T, Yonemitsu Y, Taguchi T, Sequential actions of immune effector cells induced by viral activation of dendritic cells to eliminate murine neuroblastoma., Journal of pediatric surgery, 10.1016/j.jpedsurg.2017.08.019, 53, 8, 1615-1620, 2018.08.
130. Tomoro Hishiki, Kimikazu Matsumoto, Miki Ohira, Takehiko Kamijo, Hiroyuki Shichino, Tatsuo Kuroda, Akihiro Yoneda, Toshinori Soejima, Atsuko Nakazawa, Tetsuya Takimoto, Isao Yokota, Satoshi Teramukai, Hideto Takahashi, Takashi Fukushima, Takashi Kaneko, Junichi Hara, Michio Kaneko, Hitoshi Ikeda, Tatsuro Tajiri, Akira Nakagawara, Results of a phase II trial for high-risk neuroblastoma treatment protocol JN-H-07: a report from the Japan Childhood Cancer Group Neuroblastoma Committee (JNBSG)., International journal of clinical oncology, 10.1007/s10147-018-1281-8, 23, 5, 965-973, 2018.10, BACKGROUND: The Japanese Children's Cancer Group (JCCG) Neuroblastoma Committee (JNBSG) conducted a phase II clinical trial for high-risk neuroblastoma treatment. We report the result of the protocol treatment and associated genomic aberration studies. METHODS: JN-H-07 was a single-arm, late phase II trial for high-risk neuroblastoma treatment with open enrollment from June 2007 to February 2009. Eligible patients underwent five courses of induction chemotherapy followed by high-dose chemotherapy with hematopoietic stem cell rescue. Surgery for the primary tumor was scheduled after three or four courses of induction chemotherapy. Radiotherapy was administered to the primary tumor site and to any bone metastases present at the end of induction chemotherapy. RESULTS: The estimated 3-year progression-free and overall survival rates of the 50 patients enrolled were 36.5 ± 7.0 and 69.5 ± 6.6%, respectively. High-dose chemotherapy caused severe toxicity including three treatment-related deaths. In response to this, the high-dose chemotherapy regimen was modified during the trial by infusing melphalan before administering carboplatin and etoposide. The modified high-dose chemotherapy regimen was less toxic. Univariate analysis revealed that patients younger than 547 days and patients whose tumor showed a whole chromosomal gains / losses pattern had a significantly poor prognosis. Notably, the progression-free survival of cases with MYCN amplification were not inferior to those without MYCN amplification. CONCLUSIONS: The outcome of patients treated with the JN-H-07 protocol showed improvement over the results reported by previous studies conducted in Japan. Molecular and genetic profiling may enable a more precise stratification of the high-risk cohort..
131. Paternal uniparental disomyタイプのBeckwith-Wiedemann症候群に合併した肝芽腫の1例.
132. Kawakubo N, Harada Y, Ishii M, Souzaki R, Kinoshita Y, Tajiri T, Taguchi T, Yonemitsu Y, Natural antibody against neuroblastoma of TH-MYCN transgenic mice does not correlate with spontaneous regression., Biochemical and Biophysical Research Communications, 10.1016/j.bbrc.2018.07.097, 503, 3, 1666-1673, 2018.09.
133. Tanaka T, Fumino S, Shirai T, Konishi E, Tajiri T, Mesenchymal hamartoma of the chest wall in a 10-year-old girl mimicking malignancy: a case report., Skeletal radiology, 10.1007/s00256-018-3106-2, 48, 4, 643-647, 2018.10.
134. Taizo Furukawa, Yuki Takeuchi, Tomoko Tanaka, Koichiro Yoshimaru, Tomoaki Taguchi, Tatsuro Tajiri, Localized isolated hypoganglionosis in an infant, Journal of Pediatric Surgery Case Reports, 10.1016/j.epsc.2017.09.036, 28, 48-50, 2018.01.
135. In vivo effects of short- and long-term MAPK pathway inhibition against neuroblastoma..
136. Munehiro Ohashi, Yasuhiro Umemura, Nobuya Koike, Yoshiki Tsuchiya, Yutaka Inada, Hitomi Watanabe, Tomoko Tanaka, Yoichi Minami, Osamu Ukimura, Tsuneharu Miki, Tatsuro Tajiri, Gen Kondoh, Yasuhiro Yamada, Kazuhiro Yagita, Disruption of circadian clockwork in in vivo reprogramming-induced mouse kidney tumors, Genes to Cells, 10.1111/gtc.12552, 23, 2, 60-69, 2018.02, The circadian clock, which regulates cellular physiology, such as energy metabolism, resides in each cell level throughout the body. Recently, it has been elucidated that the cellular circadian clock is closely linked with cellular differentiation. Moreover, the misregulation of cellular differentiation in mouse embryonic stem cells (ESCs) induced abnormally differentiated cells with impaired circadian clock oscillation, concomitant with the post-transcriptional suppression of CLOCK proteins. Here, we show that the circadian molecular oscillation is disrupted in dysdifferentiation-mediated mouse kidney tumors induced by partial in vivo reprogramming, resembling Wilms tumors. The expression of CLOCK protein was dramatically reduced in the tumor cells despite the Clock mRNA expression. We also showed that a similar loss of CLOCK was observed in human Wilms tumors, suggesting that the circadian molecular clockwork may be disrupted in dysdifferentiation-mediated embryonal tumors such as Wilms tumors, similar to the in vivo reprogramming-induced mouse kidney tumors. These results support our previous reports and may provide a novel viewpoint for understanding the pathophysiological nature of cancers through the correlation between cellular differentiation and circadian clock..
137. Akari Takai, Tatsuji Hasegawa, Taizo Furukawa, Tatsuro Tajiri, Hajime Hosoi, Ultrasonographic findings of multiple intussusception in an extremely preterm infant., Archives of disease in childhood, 10.1136/archdischild-2018-314885, 104, 5, 488-488, 2019.05.
138. Taizo Furukawa, Kohei Sakai, Mayumi Higashi, Shigehisa Fumino, Shigeyoshi Aoi, Tatsuro Tajiri, Thoracoscopic resection for mediastinal thymolipoma in a child., Asian journal of endoscopic surgery, 10.1111/ases.12627, 12, 2, 218-221, 2019.04, Thymolipoma is a rare disease among benign tumors. We herein report the case of a child who underwent thoracoscopic resection of a large thymolipoma. A 3-year-old boy was diagnosed with an anterior mediastinal solid tumor. Thoracic imaging revealed a fat density mass that was 8.0 × 5.0 × 3.5 cm in size. Given the MRI findings of the tumor, we suspected that the lesion was a teratoma. We decided to perform thoracoscopic exploration and, if possible, resection of the solid tumor sequentially. We successfully resected the tumor thoracoscopically. A histological examination revealed thymolipoma. For large mediastinal tumors in the intrathoracic space in children, the thoracoscopic approach is recommended when the tumor is preoperatively considered to be benign and resectable..
139. Higashi Mayumi, Sakai Kohei, Fumino Shigehisa, Aoi Shigeyoshi, Furukawa Taizo, Tajiri Tatsuro, The roles played by the MYCN, Trk, and ALK genes in neuroblastoma and neural development(和訳中), Surgery Today, 49, 9, 721-727, 2019.09.
140. A. Yoneda, T. Iehara, I. Yokota, H. Takahashi, S. Teramukai, T. Kamijo, A. Nakazawa, T. Takimoto, A. Kikuta, H. Ikeda, A. Nakagawara, T. Tajiri, The Evaluation of the New Guideline for Assessing Image-Defined Risk Factors in the Low-Risk Protocol (JN-L-10) from the Japan Children's Cancer Group Neuroblastoma Committee, PEDIATRIC BLOOD & CANCER, 66, S84-S84, 2019.12.
141. Ozeki Michio, Nozawa Akifumi, Yasue Shiho, Endo Saori, Asada Ryuta, Hashimoto Hiroya, Sozaki Ryota, Fumino Shigehisa, Furukawa Taizo, Tajiri Tatsuro, Fukao Toshiyuki, Sirolimus Treatment for Intractable Vascular Anomalies: An Interim Analysis of an Open-Label, Single-Arm, Multicenter, Prospective Study, PEDIATRIC BLOOD & CANCER, 66, S5-S5, 2019.12.
142. Tomoko Iehara, Akihiro Yoneda, Isao Yokota, Hideto Takahashi, Satoshi Teramukai, Takehiko Kamijyo, Atsuko Nakazawa, Tetsuya Takimoto, Atsushi Kikuta, Shigeki Yagyu, Hitoshi Ikeda, Akira Nakagawara, Tatsuro Tajiri, Results of a prospective clinical trial JN-L-10 using image-defined risk factors to inform surgical decisions for children with low-risk neuroblastoma disease: A report from the Japan Children's Cancer Group Neuroblastoma Committee., Pediatric blood & cancer, 10.1002/pbc.27914, 66, 11, e27914, 2019.11, BACKGROUND: The present study sought to reduce the incidence of treatment complications of low-risk neuroblastoma by using image-defined risk factors (IDRFs) to inform the timing of surgical resection. PROCEDURES: Eligible patients included children (
143. Norio Nakagawa, Ken Kikuchi, Shigeki Yagyu, Mitsuru Miyachi, Tomoko Iehara, Tatsuro Tajiri, Toshiyuki Sakai, Hajime Hosoi, Mutations in the RAS pathway as potential precision medicine targets in treatment of rhabdomyosarcoma., Biochemical and biophysical research communications, 10.1016/j.bbrc.2019.03.038, 512, 3, 524-530, 2019.05, Precision medicine strategies for treating rhabdomyosarcoma (RMS), a childhood malignancy, have not been developed. We examined the effect of CH5126766, a potent selective dual RAF/MEK inhibitor, on RMS cell lines. Among the eleven cell lines studied, one NRAS and two HRAS mutated cell lines were detected. CH5126766 inhibited the proliferation and growth in all of the RAS-mutated RMS cell lines, while it induced G1 cell cycle arrest in two of them. G1 cell cycle arrest was accompanied by p21 up-regulation and RB dephosphorylation. CH5126766 also suppressed the in vivo growth of RAS-mutated RMS tumor, and the mice showed improved survival. Thus, our results demonstrate that CH5126766 is an effective RAF/MEK inhibitor in RAS-mutated RMS. This study not only shows that in RMS, mutations in the RAS pathway can be a target for precision medicine, but also demonstrates that the evaluation of the gene mutation status is important in childhood malignancies..
144. Shigehisa Fumino, Tatsuro Tajiri, Noriaki Usui, Masanori Tamura, Haruhiko Sago, Shigeru Ono, Shunsuke Nosaka, Akihiro Yoneda, Ryota Souzaki, Mayumi Higashi, Kohei Sakai, Ken Takahashi, Takahiro Sugiura, Tomoaki Taguchi, Japanese clinical practice guidelines for sacrococcygeal teratoma, 2017., Pediatrics international : official journal of the Japan Pediatric Society, 10.1111/ped.13844, 61, 7, 672-678, 2019.07, BACKGROUND: Sacrococcygeal teratoma (SCT) is the most common extragonadal germ cell tumor in neonates and infants. Although most cases of infantile SCT are benign tumors by nature, some develop into extremely large lesions, leading to massive bleeding, high-output heart failure, disseminated intravascular coagulation, and even fatal outcomes during the neonatal period. In addition, some patients may present with tumor recurrence, malignant transformation, long-term sequelae (including bladder and bowel dysfunction) and lower leg palsy during the long-term follow up. SCT, however, is very rare, and there are few opportunities to encounter this disease, therefore general physicians without expert credentials currently lack information relevant to clinical practice. For this reason, the research project committee has compiled guidelines concerning SCT. METHODS: The purpose of these guidelines was to share information concerning the treatment and follow up of infantile SCT. The guidelines were developed using the methodologies in the Medical Information Network Distribution System. A comprehensive search of the English- and Japanese-language articles in PubMed and Ichu-Shi Web identified only case reports or case series, and the recommendations were developed through a process of informal consensus. RESULTS: The clinical questions addressed the risk factors, the efficacy of cesarean section, the initial devascularization of tumor feeding vessels, interventional radiology, recommended clinical studies for follow up and possible long-term complications. CONCLUSIONS: These are the first guidelines for SCT to be established in Japan, and they may have huge clinical value and significance in terms of developing therapeutic strategies and follow up, potentially contributing to the improvement of the prognosis and quality of life of SCT patients..
145. Akifumi Nozawa, Michio Ozeki, Shiho Yasue, Saori Endo, Norio Kawamoto, Hidenori Ohnishi, Shigehisa Fumino, Taizo Furukawa, Tatsuro Tajiri, Takanobu Maekawa, Akihiro Fujino, Ryota Souzaki, Toshiyuki Fukao, Immunologic Effects of Sirolimus in Patients With Vascular Anomalies., Journal of pediatric hematology/oncology, 10.1097/MPH.0000000000001650, 42, 5, e355-e360, 2019.11, Emerging data have suggested that sirolimus may be a treatment option for complicated vascular anomalies (VAs). The present study aimed to investigate the immunologic effects of sirolimus treatment for 6 months in patients with VAs. Blood samples obtained from the patients enrolled in 2 multicenter studies to investigate the efficacy of sirolimus for VAs before and after sirolimus treatment for 6 months were used. Data for total white blood cell count, absolute lymphocyte count, serum immunoglobulins (Igs) levels (IgG, IgA, IgM), lymphocyte proliferation assays with mitogens including phytohemagglutinin and concanavalin A, and flow cytometric analysis of lymphocyte subsets were evaluated. A total of 18 patients with VAs receiving sirolimus treatment were included in the study. Comparisons of white blood cell, absolute lymphocyte count, IgG, IgA, IgM, and reaction rates of phytohemagglutinin and concanavalin A revealed no significant differences before and after treatment. No significant differences were observed in the absolute counts of lymphocyte subtypes before and after treatment, except for regulatory T-cell counts, which were significantly decreased after treatment. Severe infections were not observed during sirolimus treatment. The immunologic parameters assessed in the present study were hardly affected by sirolimus treatment for 6 months in patients with VAs..
146. Inoue, Maho, Tsuchiya, Yoshiki, Koike, Nobuya, Umemura, Yasuhiro, Inokawa, Hitoshi, Togashi, Yuichi, Maniwa, Junnosuke, Higashi, Mayumi, Fumino, Shigehisa, Tajiri, Tatsuro, Yagita, Kazuhiro, Enhanced metastatic growth after local tumor resection in the presence of synchronous metastasis in a mouse allograft model of neuroblastoma, PEDIATRIC SURGERY INTERNATIONAL, 10.1007/s00383-019-04568-0, 35, 12, 1403-1411, 2019.12, Purpose We investigated how local tumor resection affects metastatic lesions in neuroblastoma. Methods MYCN Tg tumor-derived cells were injected subcutaneously into 129(+Ter)/SvJcl wild-type mice. First, the frequency of metastasis-bearing mice was investigated immunohistochemically (metastatic ratio) at endpoint or post-injection day (PID) 90. Second, the threshold volume of local tumor in mice bearing microscopic lymph node metastasis (mLNM) was investigated at PID 30. Finally, local tumors were resected after exceeding the threshold. Mice were divided into local tumor resection (Resection) and observation (Observation) groups, and the metastatic ratio and volume of LNM were compared between the groups at endpoint or PID 74. Results The metastatic ratio without local resection was 88% at PID 78-90. The threshold local tumor volume in the mice with mLNM was 745 mm(3) at PID 30, so local tumors were resected after exceeding 700 mm(3). The metastatic ratio and LNM volume were significantly greater in the Resection group (n = 16) than in the Observation group (n = 16) (94% vs. 38%, p
147. Ozeki, Michio, Asada, Ryuta, Saito, Akiko M., Hashimoto, Hiroya, Fujimura, Takumi, Kuroda, Tatsuo, Ueno, Shigeru, Watanabe, Shoji, Nosaka, Shunsuke, Miyasaka, Mikiko, Umezawa, Akihiro, Matsuoka, Kentaro, Maekawa, Takanobu, Yamada, Yohei, Fujino, Akihiro, Hirakawa, Satoshi, Furukawa, Taizo, Tajiri, Tatsuro, Kinoshita, Yoshiaki, Souzaki, Ryota, Fukao, Toshiyuki, Efficacy and safety of sirolimus treatment for intractable lymphatic anomalies: A study protocol for an open-label, single-arm, multicenter, prospective study (SILA), REGENERATIVE THERAPY, 10.1016/j.reth.2018.12.001, 10, 84-91, 2019.06, Introduction: Lymphatic anomalies (LAs) refer to a group of diseases involving systemic dysplasia of lymphatic vessels. These lesions are classified as cystic lymphatic malformation (macrocystic, microcystic or mixed), generalized lymphatic anomaly, and Gorham-Stout disease. LAs occur mainly in childhood, and present with various symptoms including chronic airway problems, recurrent infection, and organ disorders. Individuals with LAs often experience progressively worsening symptoms with a deteriorating quality of life. Although limited treatment options are available, their efficacy has not been validated in prospective clinical trials, and are usually based on case reports. Thus, there are no validated standards of care for these patients because of the lack of prospective clinical trials.Methods: This open-label, single-arm, multicenter, prospective study will assess the efficacy and safety of a mammalian target of the rapamycin inhibitor sirolimus in the treatment of intractable LAs. Participants will receive oral sirolimus once a day for 52 weeks. The dose is adjusted so that the nadir concentration remains within 5-15 ng/ml. The primary endpoint is the response rate of radiological volumetric change of the target lesion confirmed by central review at 52 weeks after treatment. The secondary endpoints are the response rates at 12 and 24 weeks, respiratory function, pleural effusion, ascites, blood coagulation parameters, bleeding, pain, quality of life, activities of daily living, adverse events, side effects, laboratory examinations, vital signs, and pharmacokinetic data.Results: This is among the first multicenter studies to evaluate sirolimus treatment for intractable LAs, and few studies to date have focused on the standard assessment of the efficacy for LAs treatment. Our protocol uses novel, uncomplicated methods for radiological assessment, with reference to the results of our previous retrospective survey and historical control data from the literature.Conclusions: We propose a multicenter study to investigate the efficacy and safety of sirolimus for intractable LAs (SILA study; trial registration UMIN000028905). Our results will provide pivotal data to support the approval of sirolimus for the treatment of intractable LAs. (C) 2019, The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V..
148. Kiyokazu Kim, Mayumi Higashi, Shigehisa Fumino, Tatsuro Tajiri, Derivation of neural stem cells from human teratomas., Stem cell research, 10.1016/j.scr.2019.101633, 41, 101633-101633, 2019.12, Human teratoma is a germ cell tumor that contains normal tissues (e.g., hair, skin or cartilage) differentiated from embryonal germ layers. Because of the feature of this tumor, we hypothesized that human teratomas contain multipotent stem cells that can develop into various non-cancerous normal tissues. In this study, we cultured neurospheres originally derived from a human infantile teratoma tissue, and the sphere cells were found to possess the characteristics of neural stem cells. Tumor tissues were obtained from an infantile immature teratoma at the time of surgical resection. In the primary cell culture, colonies were formed in two weeks and were individually cultured in serum-free conditioned neural stem cell medium (NSC medium). Colonies changed into spheres and grew in smooth round forms, or attached to the bottom of the dishes and extended processes and filaments around. Sphere cells were dissociated into single cells, and new spheres (secondary spheres) were formed in NSC medium. Cell differentiation was induced by culturing cells in serum-containing medium (differentiation medium), as cells spread and attached to the bottom of dishes and changed form. The expression of Nestin, Sox2, CXCR4, and (stem cell markers), β3-tubulin (a neural marker) GFAP (a glial marker) CNPase, SOX10 (oligodendrocyte markers) and NF-L in cells was analyzed by immunofluorescence and a Q-PCR. Nestin, SOX2, CXCR4 were abundant in both primary and secondary spheres. Neural and glial markers (β3-tubulin and GFAP, respectively) were increased in cells cultured in differentiation medium while stem cell markers were diminished. The oligodendrocyte markers SOX10 and CNPase were also found in both spheres and differentiated cells. In conclusion, spheres with the characteristics of neural stem cells were obtained from the primary culture of a human infantile teratoma. These spheres are considered to have the potential to undergo a natural course of neural development in humans..
149. Takayama, Shohei, Sakai, Kohei, Fumino, Shigehisa, Furukawa, Taizo, Kishida, Tsunao, Mazda, Osam, Tajiri, Tatsuro, An intra-amniotic injection of mesenchymal stem cells promotes lung maturity in a rat congenital diaphragmatic hernia model, PEDIATRIC SURGERY INTERNATIONAL, 10.1007/s00383-019-04561-7, 35, 12, 1353-1361, 2019.12, Purpose We aimed to evaluate the effect of human mesenchymal stem cells (hMSCs) on congenital diaphragmatic hernia (CDH) by intra-amniotic injection in a rat CDH model. Methods Nitrofen (100 mg) was administered to pregnant rats at E9.5. hMSCs (1.0 x 10(6)) or PBS was injected into each amniotic cavity at E18, and fetuses were harvested at E21. The fetal lungs were classified into normal, CDH, and CDH-hMSCs groups. To determine the lung maturity, we assessed the alveolar histological structure by H&E and Weigert staining and the alveolar arteries by Elastica Van Gieson (EVG) staining. TTF-1, a marker of type II alveolar epithelial cells, was also evaluated by immunohistochemical staining and real-time reverse transcription polymerase chain reaction. Results The survival rate after intra-amniotic injection was 72.1%. The CDH-hMSCs group had significantly more alveoli and secondary septa than the CDH group (p
150. Eiso Hiyama, Tomoro Hishiki, Kenichiro Watanabe, Kohmei Ida, Yuka Ueda, Sho Kurihara, Michihiro Yano, Ken Hoshino, Akiko Yokoi, Yuichi Takama, Yuki Nogami, Tomoaki Taguchi, Makiko Mori, Kentaro Kihira, Osamu Miyazaki, Hiroshi Fuji, Shohei Honda, Tomoko Iehara, Takuro Kazama, Junya Fujimura, Yukichi Tanaka, Takeshi Inoue, Tatsuro Tajiri, Satoshi Kondo, Takaharu Oue, Kenichi Yoshimura, Outcome and Late Complications of Hepatoblastomas Treated Using the Japanese Study Group for Pediatric Liver Tumor 2 Protocol., Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 10.1200/JCO.19.01067, 38, 22, JCO1901067-2498, 2020.05, PURPOSE: We report here the outcomes and late effects of the Japanese Study Group for Pediatric Liver Tumors (JPLT)-2 protocol, on the basis of cisplatin-tetrahydropyranyl-adriamycin (CITA) with risk stratification according to the pretreatment extent of disease (PRETEXT) classification for hepatoblastoma (HB). PATIENTS AND METHODS: From 1999 to 2012, 361 patients with untreated HB were enrolled. PRETEXT I/II patients were treated with up-front resection, followed by low-dose CITA (stratum 1) or received low-dose CITA, followed by surgery and postoperative chemotherapy (stratum 2). In the remaining patients, after 2 cycles of CITA, responders received the CITA regimen before resection (stratum 3), and nonresponders were switched to ifosfamide, pirarubicin, etoposide, and carboplatin (ITEC; stratum 4). Intensified chemotherapeutic regimens with autologous hematopoietic stem-cell transplantation (SCT) after resection were an optional treatment for patients with refractory/metastatic disease. RESULTS: The 5-year event-free and overall survival rates of HB patients were 74.2% and 89.9%, respectively, for stratum 1, 84.8% and 90.8%%, respectively, for stratum 2, 71.6% and 85.9%%, respectively, for stratum 3, and 59.1% and 67.3%%, respectively, for stratum 4. The outcomes for CITA responders were significantly better than those for nonresponders, whose outcomes remained poor despite salvage therapy with a second-line ITEC regimen or SCT. The late effects, ototoxicity, cardiotoxicity, and delayed growth, occurred in 61, 18, and 47 patients, respectively. Thirteen secondary malignant neoplasms (SMNs), including 10 leukemia, occurred, correlating with higher exposure to pirarubicin and younger age at diagnosis. CONCLUSION: The JPLT-2 protocol achieved up-front resectability in PRETEXT I/II patients with no annotation factors, and satisfactory survival in patients who were CITA responders in the remaining patients. However, outcomes for CITA nonresponders were unsatisfactory, despite therapy intensification with ITEC regimens and SCT. JPLT-2 had a relatively low incidence of cardiotoxicity but high rates of SMNs..
151. Yasumichi Kuwahara, Tomoko Iehara, Eisuke Ichise, Yoshiki Katsumi, Kazutaka Ouchi, Kunihiko Tsuchiya, Mitsuru Miyachi, Eiichi Konishi, Hiroyasu Sasajima, Satoaki Nakamura, Shigehisa Fumino, Tatsuro Tajiri, Pascal D Johann, Michael C FrÜhwald, Tatsushi Yoshida, Tsukasa Okuda, Hajime Hosoi, Novel Two MRT Cell Lines Established from Multiple Sites of a Synchronous MRT Patient., Anticancer research, 10.21873/anticanres.14636, 40, 11, 6159-6170, 2020.11, BACKGROUND/AIM: Malignant rhabdoid tumor (MRT) is a rare, aggressive neoplasm found in young children, caused by inactivation of a single gene, SNF5 (INI1, SMARCB1). MRT cases with multifocal tumors at diagnosis are categorized as synchronous MRT, often with a germline mutation of SNF5. The aim of this study was to establish new models useful in clarifying the biological basis of synchronous MRT. MATERIALS AND METHODS: We established two novel MRT cell lines, designated as KP-MRT-KS and KP-MRT-KSa, derived from different lesions and at a different time from a synchronous multifocal 7-month-old female MRT patient. RESULTS: Both cells showed typical morphology of MRT, with a compound genomic mutation in exons 2 and 5 of the SNF5 gene. The exon 2 mutation was found in the germline. CONCLUSION: These cell lines could serve as powerful tools for unveiling the molecular mechanism of refractory synchronous MRT..
152. So Tando, Kohei Sakai, Shohei Takayama, Kenji Fukunaga, Mayumi Higashi, Shigehisa Fumino, Shigeyoshi Aoi, Taizo Furukawa, Tatsuro Tajiri, Hiroshi Ogi, Kyoko Itoh, Maldevelopment of intrapulmonary bronchial cartilage in congenital diaphragmatic hernia., Pediatric pulmonology, 10.1002/ppul.24799, 55, 7, 1771-1780, 2020.07, BACKGROUND: Pulmonary hypoplasia is an important cause of morbidity and mortality in infants with congenital diaphragmatic hernia (CDH). This study aimed to verify our hypothesis that the abnormal development of bronchial cartilage as well as alveolar immaturity, might play a central role in hypoplasia of the lung in human CDH. METHOD: We retrospectively analyzed autopsied lungs from 10 CDH cases and compared with nine age-matched controls to assess the bronchial cartilage and alveolar maturity using morphological techniques. RESULT: Ki-67 and thyroid transcription factor-1 (TTF-1) expression in the alveoli significantly increased in bilateral lungs with CDH. The shortest distance from the bronchial cartilage to the pleura was significantly shorter in ipsilateral (left) lungs with CDH, showing a positive correlation with the radial alveolar count (RAC). Regarding the small bronchial cartilages less than 20 000 μm2 , the average cartilage area significantly decreased in left lungs with CDH, and tended to decrease in right lungs with CDH. In addition, cartilage around the bronchi less than 200 μm in diameter tended to be smaller in left lungs with CDH. In contrast, regarding the cartilage around the bronchi 200 to 400 μm in diameter, the ratio of the total cartilage area relative to the bronchial diameter tended to be higher in left lungs with CDH, although there was a large variation. CONCLUSIONS: These opposite directional cartilage abnormalities around the distal and more proximal bronchi support our hypothesis that abnormal development of bronchial cartilage might play an important role in the hypoplastic lung in CDH..
153. Mami Uemura, Mayumi Higashi, Montri Pattarapanawan, Shohei Takami, Naoki Ichikawa, Hiroki Higashiyama, Taizo Furukawa, Jun Fujishiro, Yuki Fukumura, Takashi Yao, Tatsuro Tajiri, Masami Kanai-Azuma, Yoshiakira Kanai, Gallbladder wall abnormality in biliary atresia of mouse Sox17+/- neonates and human infants., Disease models & mechanisms, 10.1242/dmm.042119, 13, 4, 2020.01, Biliary atresia (BA) is characterized by the inflammation and obstruction of the extrahepatic bile ducts (EHBDs) in newborn infants. SOX17 is a master regulator of the fetal EHBDs formation. In mouse Sox17+/- BA models, SOX17 reduction causes cell-autonomous epithelial shedding together with the ectopic appearance of SOX9-positive cystic duct-like epithelia in the gallbladder walls, resulting in the BA-like symptoms during the perinatal period. However, the similarities with the human BA gallbladders are still unclear. In the present study, we conducted the phenotypic analysis with the Sox17+/- BA neonate mice, in order to compare with the gallbladder wall phenotype of human BA infants. The most characteristic phenotype of the Sox17+/- BA gallbladders is the ectopic appearance of SOX9-positive peribiliary glands (PBGs), so-called pseudopyloric glands (PPGs). Next we examined SOX17/SOX9 expression profiles of human gallbladders in thirteen BA infants. Among them, five BA cases showed a loss or drastic reduction of SOX17-positive signals throughout the whole region of gallbladder epithelia (SOX17-low group). Even in the remaining eight gallbladders (SOX17-high group), the epithelial cells near the decidual sites were frequently reduced in the SOX17-positive signal intensity. Most interestingly, the most characteristic phenotype of human BA gallbladders is the increased density of PBG/PPG-like glands in the gallbladder body, especially near the epithelial decidual site, indicating the PBG/PPG formation as a common phenotype between human BA and mouse Sox17+/- BA gallbladders. These findings provide the first evidence of the potential contribution of SOX17 reduction and PBG/PPG formation to the early pathogenesis in human BA gallbladders..
154. 桑原 康通, 家原 知子, 勝見 良樹, 土屋 邦彦, 宮地 充, 田尻 達郎, 忠垣 憲次郎, 吉田 達士, 奥田 司, 細井 創, DANメチル化プロファイルを用いたラブドイド腫瘍患者の同時多発病変より樹立した新規2細胞株の解析, 日本癌学会総会記事, 79回, OE14-2, 2020.10.
155. Tomoko Iehara, Akihiro Yoneda, Atsushi Kikuta, Toshihiro Muraji, Kazuaki Tokiwa, Hideto Takahashi, Satoshi Teramukai, Tetsuya Takimoto, Shigeki Yagyu, Hajime Hosoi, Tatsuro Tajiri, A phase II JN-I-10 efficacy study of IDRF-based surgical decisions and stepwise treatment intensification for patients with intermediate-risk neuroblastoma: a study protocol., BMC pediatrics, 10.1186/s12887-020-02061-5, 20, 1, 212-212, 2020.05, BACKGROUND: Few clinical trials have been reported for patients with intermediate-risk neuroblastoma because of the scarcity of the disease and the variety of clinical and biological characteristics. A multidisciplinary treatment that consists of multidrug chemotherapy and surgery is expected to lead to a good prognosis with few complications. Therefore, a clinical trial for patients with intermediate-risk tumors was designed to establish a standard treatment that reduces complications and achieves good outcomes. METHODS: We planned a prospective phase 2, single-arm study of the efficacy of image-defined risk factors (IDRF)-based surgical decision and stepwise treatment intensification for patients with intermediate-risk neuroblastomas. For the localized tumor group, IDRF evaluations will be performed after each three-course chemotherapy, and surgery will be performed when appropriate. For patients with metastatic tumors, a total of five chemotherapy courses will be performed, and primary lesions will be removed when the IDRF becomes negative. The primary endpoint is 3-year progression-free survival rate, and the secondary endpoints include 3-year progression-free survival rates and overall survival rates of the localized group and the metastasis group and the incidence of adverse events. From international results, 75% is considered an appropriate 3-year progression-free survival rate. If this trial's expected 3-year progression-free survival rate of 85% is statistically greater than 75% in the lower limit of the 95.3% confidence interval, with an accuracy 10% (85 ± 10%), both groups require more than 65 patients. DISCUSSION: This study is the first clinical trial on the efficacy of IDRF-based surgical decision and stepwise treatment intensification for patients with intermediate-risk neuroblastomas. We expect that this study will contribute to the establishment of a standard treatment for patients with intermediate-risk neuroblastoma. TRIAL REGISTRATION: UMIN000004700, jRCTs051180203; Registered on December 9, 2010..
156. Miki Ohira, Yohko Nakamura, Tetsuya Takimoto, Atsuko Nakazawa, Tomoro Hishiki, Kimikazu Matsumoto, Hiroyuki Shichino, Tomoko Iehara, Hiroki Nagase, Takashi Fukushima, Akihiro Yoneda, Tatsuro Tajiri, Akira Nakagawara, Takehiko Kamijo, Retrospective Analysis of INRG Clinical and Genomic Factors for 605 Neuroblastomas in Japan: A Report from the Japan Children's Cancer Group Neuroblastoma Committee (JCCG-JNBSG)., Biomolecules, 10.3390/biom12010018, 12, 1, 2021.12, Neuroblastomas (NBs) exhibit broad and divergent clinical behaviors and tumor risk classification at diagnosis is crucial for the selection of an appropriate therapeutic strategy for each patient. The present study aimed to validate the clinical relevance of International Neuroblastoma Risk Group (INRG) prognostic and genomic markers in a Japanese NB cohort using a retrospective analysis. Follow-up data based on 30 common INRG queries in 605 NB cases diagnosed in Japan between 1990 and 2014 were collected and the genome signature of each tumor sample was integrated. As previously indicated, age, tumor stage, MYCN, DNA ploidy, the adrenals as the primary tumor site, serum ferritin and lactate dehydrogenase (LDH) levels, segmental chromosome aberrations, and the number of chromosome breakpoints (BP) correlated with lower survival rates, while the thorax as the primary tumor site and numerical chromosome aberrations correlated with a favorable prognosis. In the patient group with stage 4, MYCN non-amplified tumors (n = 225), one of the challenging subsets for risk stratification, age ≥ 18 months, LDH ≥ 1400 U/L, and BP ≥ 7 correlated with lower overall and event-free survival rates (p
157. Takafumi Kawano, Ryota Souzaki, Wataru Sumida, Tetsuya Ishimaru, Jun Fujishiro, Tomoro Hishiki, Yoshiaki Kinoshita, Hiroshi Kawashima, Hiroo Uchida, Tatsuro Tajiri, Akihiro Yoneda, Takaharu Oue, Tatsuo Kuroda, Tsugumichi Koshinaga, Eiso Hiyama, Masaki Nio, Yukihiro Inomata, Tomoaki Taguchi, Satoshi Ieiri, Laparoscopic approach for abdominal neuroblastoma in Japan: results from nationwide multicenter survey., Surgical endoscopy, 10.1007/s00464-021-08599-4, 36, 5, 3028-3038, 2021.06, BACKGROUND: Some neuroblastoma (NB) cases are suitable for minimally invasive surgery (MIS), but indication and technical issue are unclear. We assessed the current status of MIS for abdominal NB after mass screening period in Japan. METHODS: Preliminary questionnaires requesting the numbers of NB cases that underwent MIS from 2004 to 2016 were sent to 159 Japanese institutes of pediatric surgery. The secondary questionnaires were then sent to the institutions that reported MIS cases of NB in order to collect detailed data. RESULTS: One hundred and thirty-four (84.2%) institutions responded to the preliminary questionnaires, and 83 (52.2%) reported managing operative cases. The total number of operative cases was 1496. MIS was performed for 175 (11.6%) cases, of which the completed forms of 140 patients were returned, including 100 abdominal NB cases. The male/female ratio was 51/49. Forty-seven cases underwent a laparoscopic biopsy, and 2 (4.3%) cases were converted to laparotomy due to bleeding. Sixty-five cases underwent MIS for radical resection, and 7 (10.8%) were converted to laparotomy. The reasons for open conversion were bleeding and severe adhesion. Regarding open conversion, there were no significant relationships between conversion and neo-adjuvant chemotherapy, biopsies, stage, size, or MYCN amplification. We found no relationship between resectability and vascular encasement in this study. There was relationship between the resected tumor size and the patients' height, which was expressed using the following formula: [Formula: see text] (x, patients height, y, tumor size; p = 0.004219, SE: 1.55566). Postoperative complications after radical resection were recognized in 7 (10.8%) cases. CONCLUSIONS: MIS was performed in limited cases of abdominal NB. A laparoscopic biopsy with careful attention to bleeding is feasible. The resected tumor size was shown to correlate with the patients' height. Tumor size within 6 cm of maximum diameter can be resected safely..
158. Takafumi Kawano, Ryota Souzaki, Wataru Sumida, Naoki Shimojima, Tomoro Hishiki, Yoshiaki Kinoshita, Hiroo Uchida, Tatsuro Tajiri, Akihiro Yoneda, Takaharu Oue, Tatsuo Kuroda, Seiichi Hirobe, Tsugumichi Koshinaga, Eiso Hiyama, Masaki Nio, Yukihiro Inomata, Tomoaki Taguchi, Satoshi Ieiri, Current thoracoscopic approach for mediastinal neuroblastoma in Japan-results from nationwide multicenter survey., Pediatric surgery international, 10.1007/s00383-021-04998-9, 37, 12, 1651-1658, 2021.08, BACKGROUND: Minimally invasive surgery (MIS) is appropriate for the treatment of some neuroblastomas (NBs); however, the indications and technical issues are unclear. This study aimed to clarify the current status of MIS for mediastinal NB in Japan. METHODS: Preliminary questionnaires requesting the numbers of neuroblastoma cases in which MIS was performed from 2004 to 2016 were sent to 159 Japanese institutes of pediatric surgery. Secondary questionnaires were sent to institutions with MIS cases to collect detailed data. RESULTS: One hundred thirty-four (84.2%) institutions returned the preliminary questionnaire and 83 institutions (52.2%) reported a total of 1496 operative cases. MIS was performed for 175 (11.6%) cases. Among the 175 cases, completed forms of 140 patients were returned and 40 (male, n = 28; female, n = 12) cases had mediastinal NB. Fourteen patients received thoracoscopic biopsy, none were converted to thoracotomy. Twenty-eight patients received MIS for radical resection, none were converted to thoracotomy. Perioperative complications (Horner's syndrome) were recognized after radical resection in one (2.5%) case. CONCLUSIONS: MIS was performed in a limited number of mediastinal NB cases. A thoracoscopic approach would be feasible for mediastinal NB..
159. Koichiro Yoshimaru, Akihiko Tamaki, Toshiharu Matsuura, Kenichi Kohashi, Keisuke Kajihara, Keiko Irie, Yuko Hino, Yasuyuki Uchida, Yukihiro Toriigahara, Yuki Kawano, Takeshi Shirai, Yoshinao Oda, Tatsuro Tajiri, Tomoaki Taguchi, Palisading-like arrangement of immature ganglion cell in myenteric ganglia is a unique pathological feature of immaturity of ganglia., Journal of pediatric surgery, 10.1016/j.jpedsurg.2022.02.035, 57, 7, 1269-1273, 2022.07, BACKGROUND: Immaturity of ganglia (IG), an allied disorder of Hirschsprung disease (AD-HSCR), develops as neonatal ileus, but the dysmotility spontaneously resolves after several months. The diagnosis of IG using HE staining is often difficult. We herein report a new pathological finding of IG called the 'palisading-like pattern', which may be helpful for improving the diagnostic accuracy. METHODS: Cases of IG that were managed over the past 28 years were retrospectively reviewed. We investigated the clinical course and pathological findings for Hematoxylin-Eosin (HE) staining. The conventional diagnostic criteria for IG were (1) a normal or slightly increased number of ganglion cells and (2) ganglion cells with small nuclei. RESULTS: Among the 155 cases, 28 were diagnosed with IG, and 10 were retrospectively confirmed by HE staining. A palisading-like pattern was confirmed at the time of the initial ileostomy (median age, 2.5 days), and the palisading-like pattern had completely disappeared by the time of stoma closure (median age, 215 days) in all 10 cases. A palisading-like pattern is not present in other diseases. CONCLUSIONS: Even if immunostaining data are not available for a further analysis, the detection of a palisading-like pattern on HE staining makes an accurate diagnosis possible. LEVEL OF EVIDENCE: LEVEL IV..
160. Junichi Hara, Chika Nitani, Hiroyuki Shichino, Tatsuo Kuroda, Tomoro Hishiki, Toshinori Soejima, Tetsuya Mori, Kimikazu Matsumoto, Yoji Sasahara, Tomoko Iehara, Takako Miyamura, Yoshiyuki Kosaka, Tetsuya Takimoto, Akira Nakagawara, Tatsuro Tajiri, Outcome of children with relapsed high-risk neuroblastoma in Japan and analysis of the role of allogeneic hematopoietic stem cell transplantation., Japanese journal of clinical oncology, 10.1093/jjco/hyac007, 52, 5, 486-492, 2022.05, BACKGROUND: In Japan, allogeneic hematopoietic stem cell transplantation is widely performed for recurrent neuroblastomas. This retrospective study aimed to investigate the prognosis of recurrent neuroblastoma in Japan and explore the effectiveness of allogeneic hematopoietic stem cell transplantation. METHODS: Clinical characteristics and data on the treatment of patients with high-risk neuroblastoma who experienced first progression between 2003 and 2010 after attaining complete remission or partial remission were collected from hospitals participating in the Japanese Neuroblastoma Research Group. RESULTS: Data from 61 patients who fulfilled these criteria were collected. The median interval from disease onset to first progression was 19 months (range, 7-65 months), whereas the median observation time of the surviving patients was 18 months (range, 1-69 months). All patients were treated with chemotherapy, where 22 and 3 patients received allogeneic and autologous hematopoietic stem cell transplantation, respectively. Seven patients were alive in second complete remission, and 39 died, including two in complete remission. The 3-year progression-free survival and overall survival rates were 15.3% (SE: 6.1%) and 16.9% (SE: 6.5%), respectively. For patients with allogeneic hematopoietic stem cell transplantation, the 3-year progression-free survival and overall survival were 28.3% (standard error, 12.0%) and 24.3% (standard error, 11.5%), respectively, and for patients without allogeneic hematopoietic stem cell transplantation, the 3-year progression-free survival and overall survival were 6.0% (standard error 5.5%) and 12.0% (standard error 7.6%), respectively. The duration of initial remission (≥ 18 months) and implementation of allogeneic hematopoietic stem cell transplantation were independently predictive of progression-free survival (P = 0.002 and P = 0.017), whereas for overall survival, only allogeneic hematopoietic stem cell transplantation was predictive (P = 0.012). CONCLUSION: Although allogeneic hematopoietic stem cell transplantation contributed to some improvement in prognosis, it was insufficient..