論文

Purpose: The aim of this study was to study the prognostic significance of circulating tumor cells (CTC) and the appropriate indications for aggressive surgery in advanced neuroblastoma. Materials and Methods: Micrometastasis was sequentially explored using our reverse transcriptase-polymerase chain reaction method in 29 neuroblastoma patients (International Neuroblastoma Staging System stage 4, n = 24; stage 3, n = 5) who treated at our department with the united chemotherapeutic regimen since 1991. Their medical records and detection of CTC and/or the bone marrow micrometastasis were retrospectively reviewed then analyzed statistically. Results: The overall survival rate was 58.6% (17/29). Circulating tumor cells were detected in 55.6% of the stage 4 patients, and all deaths were related to systemic metastases in the CTC-positive patients. The detection of CTC scarcely associated with MYCN amplification. In the patients showing MYCN amplification but no CTC, all deaths were related to local relapse or chemotherapy-associated complications. The survival rate was not significantly different between the patients with and without MYCN amplification (56.8% vs 52.7%). However, it was significantly lower in the patients with CTC and/or persistent bone marrow micrometastasis compared to those without detectable micrometastasis (33.8% vs 87.5%; P < .05). Conclusions: The presence of CTC and/or persistent micrometastasis may indicate a significantly high risk, regardless of MYCN amplification. Patients with MYCN amplification but no micrometastasis would be most benefited by highly intensive surgery. © 2008 Elsevier Inc. All rights reserved.

One of the most serious problems in patients with long-gap esophageal atresia or corrosive esophagitis is esophageal stricture, which may require esophageal resection and replacement. We describe two cases with persistent esophageal stricture successfully managed by high dose intravenous methylprednisolone following balloon dilatation. High-dose methylprednisolone with gradual tapering (daily 25, 15, 10, 5, 2 mg/kg for 4 days each) plus cimetidine and ampicillin for 1 week was intravenously administrated immediately after balloon dilatation of the esophageal stenosis. This was followed by oral prednisolone (daily 2, 1, 0.5 mg/kg for 1 week each) for persistent esophageal stricture. High dose intravenous methylprednisolone therapy was given to two patients. One patient was a 5-year-old boy with long-gap esophageal atresia who had undergone repair of the esophagus resulting in severe anastomotic stenosis of 3 cm in length. The other case was a 10-year-old boy with corrosive stenosis caused by alkali ingestion. Both patients had been requiring balloon dilatation of the esophagus with intralesional injection of dexamethasone every 3 weeks for more than 1 year to tolerate oral feeding. After the high-dose methylprednisolone protocol was initiated, the symptoms of dysphagia or choking dramatically improved in both patients, and they remained symptom-free for 8 and 7 months. There were complications of moon faces that resolved concomitantly with the withdrawal of oral prednisolone in both cases. High dose intravenous methylprednisolone in addition to intralesional injection of dexamethasone following balloon dilation is an effective therapeutic strategy for persistent esophageal strictures. © 2008 Springer-Verlag.

Ovulation induces cyclic rupture and regenerative repair of the ovarian coelomic epithelium. This process of repeated disruption and repair accompanied by complex remodeling typifies a somatic stem/progenitor cell-mediated process. Using BrdU incorporation and doxycycline inducible histone2B-green fluorescent protein pulse-chase techniques, we identify a label-retaining cell population in the coelomic epithelium of the adult mouse ovary as candidate somatic stem/progenitor cells. The identified population exhibits quiescence with asymmetric label retention, functional response to estrous cycling in vivo by proliferation, enhanced growth characteristics by in vitro colony formation, and cytoprotective mechanisms by enrichment for the side population. Together, these characteristics identify the label-retaining cell population as a candidate for the putative somatic stem/progenitor cells of the coelomic epithelium of the mouse ovary. © 2008 by The National Academy of Sciences of the USA.

巨大仙尾部奇形腫(SCT)の新生児期手術と周術期管理について検討した。胎児SCTは9例で、1例が妊娠中断、8例が帝王切開分娩となった。腫瘍切除術は平均日齢5.25に施行され1例が死亡、7例が生存退院した。胎児水腫合併2例中、1例は妊娠20週にSCTを疑われた。出生後は腫瘤内出血により循環動態が不安定で、同日摘出術を施行したが術中大量出血による心停止を繰り返し術中死した。残りの1例は妊娠24週にSCTを疑われた。妊娠30週4日に全身麻酔下に母体に超音波ガイド下で経皮的に穿刺針を腫瘍内の栄養血管周囲に刺入し、RFAを施行した。術後胎児心拍出量の低下を認め、腫瘍の増大は止まった。日齢4に腫瘍切除術を施行した。術後経過は順調で日齢73に退院となった。

Kawasaki disease is a pediatric systemic vasculitis of unknown etiology for which a genetic influence is suspected. We identified a functional SNP (itpkc_3) in the inositol 1,4,5-trisphosphate 3-kinase C (ITPKC) gene on chromosome 19q13.2 that is significantly associated with Kawasaki disease susceptibility and also with an increased risk of coronary artery lesions in both Japanese and US children. Transfection experiments showed that the C allele of itpkc_3 reduces splicing efficiency of the ITPKC mRNA. ITPKC acts as a negative regulator of T-cell activation through the Ca2+/NFAT signaling pathway, and the C allele may contribute to immune hyper-reactivity in Kawasaki disease. This finding provides new insights into the mechanisms of immune activation in Kawasaki disease and emphasizes the importance of activated T cells in the pathogenesis of this vasculitis. © 2008 Nature Publishing Group.

当科で2007年7月までに経験した新生児消化管出血46例について臨床的検討を行った。原疾患は胃破裂が最も多く19例(41%)、次いで中腸軸捻転5例(11%)、胃穿孔4例(9%)、十二指腸穿孔3例(7%)、新生児メレナ3例(7%)の順であった。出生時体重を疾患別にみると胃破裂群は他の疾患より軽い傾向にあり、2500g未満の7例は全て胃破裂であった。一方、中腸軸捻転群は重い傾向にあり、胃破裂群とは有意差が認められた。入院時日齢を疾患別にみると、胃破裂や胃穿孔は日齢4日前後であるのに対して新生児メレナは日齢1日前後と早期に入院していた。症状を疾患別にみると、新生児メレナとアレルギー性疾患では下血や血便が多く、上部消化管穿孔性疾患では吐血や経鼻胃管からの出血が多いという特徴が認められた。

In our search for genes required for the development and function of mouse gonads, we identified Gng13 (guanine nucleotide binding protein 13, gamma), a gene with an embryonic expression pattern highly restricted to the ovary. Based on reverse transcriptase-polymerase chain reaction (RT-PCR) and whole-mount in situ hybridization, Gng13 is expressed in both XX and XY gonads at embryonic day (E) 11.5, but becomes up-regulated in the XX gonad by E12.5. Expression is retained after treatment with busulfan, a chemical known to eliminate germ cells, pointing to the soma as a site of Gng13 transcription. In situ hybridization of embryonic ovarian tissue sections further localized the expression to the cortex of the developing XX gonad. Gng13 expression in the adult is also highly restricted. Northern blot analyses and Genomic Institute of the Novartis Research Foundation expression profiling of adult tissues detected very high expression in the cerebrum and cerebellum, in addition to, a weaker signal in the ovary. Gng13 belongs to a well-known family of signal transduction molecules with functions in many aspects of development and organ physiology. Here, we report that, in the developing mouse embryo, expression of Gng13 mRNA is highly restricted to the cortex of the XX gonad during sexual differentiation, suggesting a role for this gene during ovarian development. © 2007 Wiley-Liss, Inc.

During our search for genes required for gonadal development and function in the mouse, we identified D6Mm5e (DNA segment, Chr 6. Miriam Meisler 5, expressed), a gene with an expression pattern highly restricted to the embryonic ovary and the postnatal testis. Based on RT-PCR, Northern blot, and in situ hybridization analyses, we show that D6Mm5e is expressed in the germ cells of the female embryo upon their initial entry into meiosis, and in male germ cells during the last stages of spermatogenesis. Two transcripts are detected in the gonads resulting from the alternative splicing of exon 8. This splicing event does not introduce a frame shift, and creates an mRNA product that uses the same stop codon as the longer transcript. Although D6Mm5e does not belong to any known protein family and does not contain any known protein signature motifs, the high level of evolutionary conservation and the cellular and temporal expression suggest that D6Mm5e may have a role in male and female gametogenesis. Here we report the gonad-restricted mRNA expression profile of D6Mm5e in the mouse, and the evolutionary conservation of its amino acid sequence. © 2006 Wiley-Liss, Inc.

Examination of Müllerian inhibiting substance (MIS) signaling in the rat in vivo and in vitro revealed novel developmental stage- and tissue-specific events that contributed to a window of MIS responsiveness in Müllerian duct regression. The MIS type II receptor (MISRII)-expressing cells are initially present in the coelomic epithelium of both male and female urogenital ridges, and then migrate into the mesenchyme surrounding the male Müllerian duct under the influence of MIS. Expression of the genes encoding MIS type I receptors, Alk2 and Alk3, is also spatiotemporally controlled; Alk2 expression appears earlier and increases predominantly in the coelomic epithelium, whereas Alk3 expression appears later and is restricted to the mesenchyme, suggesting sequential roles in Müllerian duct regression. MIS induces expression of Alk2, Alk3 and Smad8, but downregulates Smad5 in the urogenital ridge. Alk2-specific small interfering RNA (siRNA) blocks both the transition of MISRII expression from the coelomic epithelium to the mesenchyme and Müllerian duct regression in organ culture. Müllerian duct regression can also be inhibited or accelerated by siRNA targeting Smad8 and Smad5, respectively. Thus, the early action of MIS is to initiate an epithelial-to-mesenchymal transition of MISRII-expressing cells and to specify the components of the receptor/SMAD signaling pathway by differentially regulating their expression.

＜Key Points＞(1)HPSは噴水状嘔吐を主訴とし新生児から乳児期に発症する。(2)診断は病歴と腹部超音波検査で容易に行うことができる。(3)治療は従来の手術療法と硫アトによる内科的治療がある。それぞれに利点・欠点があるため、家族の意向も考慮しつつ選択する必要がある。(著者抄録)

【目的】長期留置型の中心静脈カテーテル(CVC)は小腸不全患児にとって生命維持に必要なlife lineであり、カテーテル関連血流感染症(CRBSI)は最も重篤な合併症の一つである。今回、CRBSIに対しエタノールロック療法(ELT)を施行し、CVC温存が可能であった症例を検討したので報告する。【対象と方法】国立成育医療研究センター外科において2008年1月から2010年6月までに生後3ヵ月以上でCRBSIの診断に至った11症例に対し、のべ21件のELTが施行され、これらを対象として診療録をもとに後方視的に検討を行った。【結果】21件中17件(81%)でELT治療が成功したと判断された。CRBSIの原因菌はグラム陽性菌が71%、グラム陰性菌が19%、真菌が10%であった。真菌はすべて治療成功例であった。また成功例はすべて、治療終了後28日未満での再発を認めていない。また有害事象は、頭痛や酩酊状態など軽症例で、新たに治療が必要となるような重篤な有害事象は認めなかった。【結論】エタノールロック療法はカテーテル温存療法としてCRBSIに対して有効かつ安全な治療法であることが示唆された。一方で長期的な問題を生じる可能性等については不明な点もあり、今後も症例の蓄積が必要である。(著者抄録)

To determine the most appropriate treatment strategy for neonates with coexisting congenital heart diseases (CHD) requiring surgery, 408 neonates treated in our department between 2002 and 2009 were retrospectively reviewed. Of the 408 neonates, 37 (9.1%) had coexisting CHD. Among the pediatric diseases requiring surgery, esophageal atresia (46.7%), anorectal malformation (24.1%), and tracheobronchial anomalies (75.0%) were frequently associated with CHD, and the survival rate among patients with coexisting CDH was 24.3%, about 2-fold higher than among those without coexisting CHD. Clinical observations in the present series suggested that fatal conditions such as tracheoesophageal fistula should be repaired immediately after birth, followed by palliative cardiac surgery to stabilize the circulatory status if necessary. Thereafter, radical repair of cardiac and pediatric anomalies should be performed, taking into account the balance between surgical stress and cardiac reserve. For this purpose, proper assessment of surgical stress and cardiac function and collaboration among specialists in relevant fields are essential during the perinatal period to determine the treatment strategy for patients with multiple-organ anomalies.