RESUMO
The prognosis of patients with osteosarcoma who experience recurrence or progression (R/P) is extremely poor, and more effective and less toxic therapies are needed. In the current study, the clinical data of osteosarcoma patients who experienced R/P were retrospectively analyzed to verify the reliability of O-6-methylguanine-DNA methyltransferase (MGMT) protein expression or MGMT promoter methylation for predicting the response to off-label temozolomide (TMZ)-containing chemotherapy. Of the 30 evaluable patients, 9 (30%) showed no/low MGMT protein expression, whereas all 16 evaluable patients had unmethylated MGMT promoter irrespective of MGMT protein expression levels. Twenty-three patients received TMZ-containing chemotherapy for measurable lesions (n = 14) or as adjuvant therapy following resection of recurrent lesions (n = 9). Among 14 patients with radiologically measurable lesions, the objective response rate was higher in the MGMT no/low-expression group (50.0%) than in the MGMT intermediate/high-expression group with borderline significance (0%, p = 0.066). The 6-month progression-free survival (PFS) rate in patients with radiologically measurable lesions was significantly higher in the MGMT no/low-expression group (50.0%) than in the MGMT intermediate/high-expression group (0%, p = 0.036). In the multivariate analysis of the 23 patients receiving TMZ-containing chemotherapy, MGMT expression and disease status before TMZ-containing chemotherapy were significantly associated with PFS. No severe adverse effects were observed during TMZ-containing chemotherapy. MGMT protein expression, but not MGMT promoter methylation, could predict a favorable outcome in patients receiving TMZ-containing chemotherapy.
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Novel therapeutic strategies are urgently required for osteosarcoma, given the early age at onset and persistently high mortality rate. Modern transcriptomics techniques can identify differentially expressed genes (DEGs) that may serve as biomarkers and therapeutic targets, so we screened for DEGs in osteosarcoma. We found that osteosarcoma cases could be divided into fair and poor survival groups based on gene expression profiles. Among the genes upregulated in the poor survival group, siRNA-mediated knockdown of the glycosylation-related gene C1GALT1 suppressed osteosarcoma cell proliferation in culture. Gene expression, phosphorylation, and glycome array analyses also demonstrated that C1GALT1 is required to maintain ERK signaling and cell cycle progression. Moreover, the C1GALT1 inhibitor itraconazole suppressed osteosarcoma cell proliferation in culture, while doxycycline-induced shRNA-mediated knockdown reduced xenograft osteosarcoma growth in mice. Elevated C1GALT1 expression is a potential early predictor of poor prognosis, while pharmacological inhibition may be a feasible treatment strategy for osteosarcoma.
Assuntos
Ciclo Celular , Proliferação de Células , Galactosiltransferases , Sistema de Sinalização das MAP Quinases , Osteossarcoma , Osteossarcoma/genética , Osteossarcoma/tratamento farmacológico , Osteossarcoma/patologia , Osteossarcoma/metabolismo , Humanos , Galactosiltransferases/genética , Galactosiltransferases/metabolismo , Animais , Proliferação de Células/efeitos dos fármacos , Camundongos , Ciclo Celular/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Linhagem Celular Tumoral , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Masculino , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Camundongos NusAssuntos
Púrpura Trombocitopênica Idiopática , Receptores Fc , Proteínas Recombinantes de Fusão , Trombopoetina , Humanos , Lactente , Masculino , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Receptores Fc/uso terapêutico , Receptores de Trombopoetina/agonistas , Proteínas Recombinantes de Fusão/uso terapêutico , Trombopoetina/uso terapêuticoRESUMO
ABSTRACT: Aberrant micro-RNA (miRNA) expression profiles have been associated with disease progression and clinical outcome in pediatric cancers. However, few studies have analyzed genome-wide dysregulation of miRNAs and messenger RNAs (mRNAs) in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL). To identify novel prognostic factors, we comprehensively investigated miRNA and mRNA sequencing (miRNA-seq and mRNA-seq) data in pediatric BCP-ALL samples with poor outcome. We analyzed 180 patients, including 43 matched pairs at diagnosis and relapse. Consensus clustering of miRNA expression data revealed a distinct profile characterized by mainly downregulation of miRNAs (referred to as an miR-low cluster [MLC]). The MLC profile was not associated with any known genetic subgroups. Intriguingly, patients classified as MLC had significantly shorter event-free survival (median 21 vs 33 months; log-rank P = 3 ×10-5). Furthermore, this poor prognosis was retained even in hyperdiploid ALL. This poor prognostic MLC profiling was confirmed in the validation cohort. Notably, non-MLC profiling at diagnosis (n = 9 of 23; Fisher exact test, P = .039) often changed into MLC profiling at relapse for the same patient. Integrated analysis of miRNA-seq and mRNA-seq data revealed that the transcriptional profile of MLC was characterized by enrichment of MYC target and oxidative phosphorylation genes, reduced intron retention, and low expression of DICER1. Thus, our miRNA-mRNA integration approach yielded a truly unbiased molecular stratification of pediatric BCP-ALL cases based on a novel prognostic miRNA signature, which may lead to better clinical outcomes.
Assuntos
Linfoma de Burkitt , MicroRNAs , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Humanos , Criança , MicroRNAs/genética , MicroRNAs/metabolismo , RNA-Seq , Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Recidiva , RNA Mensageiro/genética , Ribonuclease III , RNA Helicases DEAD-boxRESUMO
There is no clear consensus on the most effective treatment for relapsed/refractory high-risk neuroblastoma (NB). We retrospectively assessed seven NB patients with relapsed/refractory disease who received high-dose carboplatin-irinotecan-temozolomide (HD-CIT). Five of seven patients showed favorable therapeutic response (complete remission or partial remission). Regarding toxicity, the cytopenia period tended to prolong when more than three cycles were repeated, but nonhematological toxicities were controllable with general supportive care. Due to its antitumor efficacy and well-tolerated nonhematologic toxicity, HD-CIT is a promising salvage chemotherapy for relapsed/refractory NB. However, it is important to pay attention to the exacerbation of hematological toxicity when repeating the regimen.
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Neuroblastoma , Humanos , Carboplatina , Irinotecano , Temozolomida , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica , Terapia de Salvação , Recidiva Local de NeoplasiaRESUMO
Neuroblastoma (NB) and pheochromocytoma (PCC) are derived from neural crest cells (NCCs); however, composite tumors with NB and PCC are rare, and their underlying molecular mechanisms remain unknown. To address this issue, we performed exome and transcriptome sequencing with formalin-fixed paraffin-embedded (FFPE) samples from the NB, PCC, and mixed lesions in a patient with a composite tumor. Whole-exome sequencing revealed that most mutations (80%) were shared by all samples, indicating that NB and PCC evolved from the same clone. Notably, all samples harbored both mutation and focal amplification in the FGFR1 oncogene, resulting in an extraordinarily high expression, likely to be the main driver of this tumor. Transcriptome sequencing revealed undifferentiated expression profiles for the NB lesions. Considering that a metastatic lesion was also composite, most likely, the primitive founding lesions should differentiate into both NB and PCC. This is the first reported case with composite-NB and PCC genetically proven to harbor an oncogenic FGFR1 alteration of a common cellular origin.
Assuntos
Neoplasias das Glândulas Suprarrenais , Neuroblastoma , Feocromocitoma , Neoplasias das Glândulas Suprarrenais/genética , Neoplasias das Glândulas Suprarrenais/patologia , Humanos , Mutação , Neuroblastoma/genética , Neuroblastoma/patologia , Oncogenes , Feocromocitoma/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genéticaRESUMO
Due to the considerable success of cancer immunotherapy for leukemia, the tumor immune environment has become a focus of intense research; however, there are few reports on the dynamics of the tumor immune environment in leukemia. Here, we analyzed the tumor immune environment in pediatric B cell precursor acute lymphoblastic leukemia by analyzing serial bone marrow samples from nine patients with primary and recurrent disease by mass cytometry using 39 immunophenotype markers, and transcriptome analysis. High-dimensional single-cell mass cytometry analysis elucidated a dynamic shift of T cells from naïve to effector subsets, and clarified that, during relapse, the tumor immune environment comprised a T helper 1-polarized immune profile, together with an increased number of effector regulatory T cells. These results were confirmed in a validation cohort using conventional flow cytometry. Furthermore, RNA transcriptome analysis identified the upregulation of immune-related pathways in B cell precursor acute lymphoblastic leukemia cells during relapse, suggesting interaction with the surrounding environment. In conclusion, a tumor immune environment characterized by a T helper 1-polarized immune profile, with an increased number of effector regulatory T cells, could contribute to the pathophysiology of recurrent B cell precursor acute lymphoblastic leukemia. This information could contribute to the development of effective immunotherapeutic approaches against B cell precursor acute lymphoblastic leukemia relapse.
Assuntos
Biomarcadores Tumorais/genética , Medula Óssea/imunologia , Perfilação da Expressão Gênica/métodos , Recidiva Local de Neoplasia/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Adolescente , Medula Óssea/química , Criança , Pré-Escolar , Feminino , Citometria de Fluxo , Regulação Neoplásica da Expressão Gênica , Humanos , Lactente , Masculino , Recidiva Local de Neoplasia/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/imunologia , Análise de Sequência de RNA , Análise de Célula Única , Microambiente Tumoral , Regulação para Cima , Adulto JovemRESUMO
Bone marrow necrosis (BMN) describes necrosis of the myeloid tissues without cortical bone involvement. Imatinib, a tyrosine kinase inhibitor, can trigger BMN during the treatment of malignant disease. In such cases, it is necessary to reduce imatinib dose or discontinue its administration, which could influence treatment outcomes. Here, we report a 6-year-old boy with Philadelphia chromosome-positive acute lymphoblastic leukemia, who developed BMN in response to imatinib. We replaced imatinib with dasatinib, and necrotic lesions gradually disappeared and were never exacerbated. In Philadelphia chromosome-positive acute lymphoblastic leukemia with BMN, tyrosine kinase inhibitor replacement may allow continued chemotherapy without intensity reduction.
Assuntos
Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras , Medula Óssea , Criança , Humanos , Mesilato de Imatinib/uso terapêutico , Masculino , Necrose , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Inibidores de Proteínas Quinases/uso terapêuticoRESUMO
Neuroblastoma, the most common extracranial solid tumor of childhood, is thought to arise from neural crest-derived immature cells. The prognosis of patients with high-risk or recurrent/refractory neuroblastoma remains quite poor despite intensive multimodality therapy; therefore, novel therapeutic interventions are required. We examined the expression of a cell adhesion molecule CD146 (melanoma cell adhesion molecule [MCAM]) by neuroblastoma cell lines and in clinical samples and investigated the anti-tumor effects of CD146-targeting treatment for neuroblastoma cells both in vitro and in vivo. CD146 is expressed by 4 cell lines and by most of primary tumors at any stage. Short hairpin RNA-mediated knockdown of CD146, or treatment with an anti-CD146 polyclonal antibody, effectively inhibited growth of neuroblastoma cells both in vitro and in vivo, principally due to increased apoptosis via the focal adhesion kinase and/or nuclear factor-kappa B signaling pathway. Furthermore, the anti-CD146 polyclonal antibody markedly inhibited tumor growth in immunodeficient mice inoculated with primary neuroblastoma cells. In conclusion, CD146 represents a promising therapeutic target for neuroblastoma.
Assuntos
Anticorpos/uso terapêutico , Antígeno CD146/antagonistas & inibidores , Terapia de Alvo Molecular/métodos , Neuroblastoma/terapia , RNA Interferente Pequeno/uso terapêutico , Animais , Apoptose , Antígeno CD146/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular , Quinase 1 de Adesão Focal/metabolismo , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Técnicas de Silenciamento de Genes , Xenoenxertos , Humanos , Camundongos , NF-kappa B/metabolismo , Recidiva Local de Neoplasia , Transplante de Neoplasias , Neuroblastoma/metabolismo , Neuroblastoma/patologia , Prognóstico , Transdução de Sinais , Esferoides Celulares , Transdução Genética/métodosRESUMO
Growing teratoma syndrome is a well-recognized condition associated with both intracranial and extracranial nongerminomatous germ cell tumors (NGGCTs), which mostly manifest as rapid growth of cystic and solid components during or within several months after treatment. Here, we report a patient with NGGCT who experienced slow growth of intracranial growing teratoma syndrome with intraventricular lipid accumulation over 10 years without any clinical symptoms. Considering the clinicopathologic heterogeneity of this syndrome, long-term clinical and radiologic follow-up is required for all patients with intracranial NGGCT.
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Neoplasias Encefálicas/patologia , Lipídeos/análise , Teratoma/patologia , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/metabolismo , Pré-Escolar , Humanos , Metabolismo dos Lipídeos , Masculino , Pinealoma/diagnóstico , Pinealoma/metabolismo , Pinealoma/patologia , Teratoma/diagnóstico , Teratoma/metabolismoAssuntos
Braquiterapia/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/etiologia , Neoplasias Primárias Múltiplas/terapia , Neoplasias Induzidas por Radiação/etiologia , Segunda Neoplasia Primária/etiologia , Radioterapia Adjuvante/efeitos adversos , Retinoblastoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Crioterapia , Dasatinibe/uso terapêutico , Enucleação Ocular , Humanos , Lactente , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Fotocoagulação , Masculino , Melfalan/uso terapêutico , Neoplasias Induzidas por Radiação/tratamento farmacológico , Segunda Neoplasia Primária/tratamento farmacológico , Indução de RemissãoRESUMO
Compared to cerebral radiation-induced cavernous hemangiomas (RICHs), little is known about intraspinal RICHs. A 13-year-old male suddenly developed symptomatic spinal hemorrhage eight years after hematopoietic stem cell transplantation using a total body irradiation (TBI) based myeloablative regimen. A solitary small hemangioma was detected on follow-up T2 star weighted magnetic resonance imaging of the spine. His neurological symptoms gradually improved with supportive treatment and rehabilitation, although he experienced rebleeding 2 years later. Intraspinal RICH is very rare but should be recognized as a possible late adverse effect in pediatric patients who received TBI.
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Hemangioma Cavernoso do Sistema Nervoso Central/etiologia , Hemorragia/etiologia , Neoplasias Induzidas por Radiação/etiologia , Neoplasias da Medula Espinal/etiologia , Irradiação Corporal Total/efeitos adversos , Adolescente , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapiaRESUMO
BKV-HC is a serious complication of allogeneic HSCT. To characterize the incidence, risk factors, and clinical outcomes of post-HSCT BKV-HC, we retrospectively analyzed 112 patients who underwent one or more allogeneic HSCTs at our hospital between 2001 and 2017. Twenty underwent second or third HSCT thereafter. Ten patients developed BKV-HC at a median of 30 days after HSCT. The 100-day cumulative incidences of grade 0-4 and grade 2-4 BKV-HC were 7.8% and 6.2%, respectively. HSCTs performed in 2011-2017 associated with significantly higher 100-day cumulative incidence of grade 2-4 BKV-HC (14.0%) than HSCTs performed in 2001-2010 (1.3%, P = 0.004). On multivariate analysis, second or third HSCT was the only independent significant risk factor for development of grade 2-4 BKV-HC (P = 0.015). Serial PCR monitoring of urine and blood BKV load did not predict BKV-HC. The recent increase in the incidence of BKV-HC may reflect recent innovations in transplant technologies that facilitate second or third HSCT, which are known to cause prolonged immune deficiency. If safe and effective treatment or prophylaxis becomes available, it could be used to target the high-risk patients for BKV-HC.
Assuntos
Vírus BK , Cistite/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hemorragia/etiologia , Infecções por Polyomavirus/etiologia , Infecções Tumorais por Vírus/etiologia , Adolescente , Criança , Pré-Escolar , Cistite/diagnóstico , Cistite/epidemiologia , Feminino , Seguimentos , Hemorragia/diagnóstico , Hemorragia/epidemiologia , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Análise Multivariada , Infecções por Polyomavirus/diagnóstico , Infecções por Polyomavirus/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Transplante Homólogo , Infecções Tumorais por Vírus/diagnóstico , Infecções Tumorais por Vírus/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Information on long-term follow up of childhood-onset anorexia nervosa is scarce. This study investigated long-term (>10 years) course, outcome and prognostic factors for hospitalized childhood-onset anorexia nervosa restricting type (ANR). METHODS: Forty-one ANR girls admitted to a single regional center participated. Median age at first admission was 13.3 years (range, 8.6-15.6 years). The longitudinal clinical course was retrospectively determined for a median follow-up period of 17.1 years (range, 10.4-21.1 years). We analyzed physical, psychological, and social variables to predict partial remission (PR) and full remission (FR). RESULTS: The completion rate of follow up >10 years was high at 97%. At final evaluation (n = 38), distribution of prognosis was as follows: FR, n = 27 (71%); PR, n = 6 (16%); and non-remission, n = 5 (13%). The cumulative ratio of PR and FR increased during the first 5-6 years, and gradually reached a plateau at around 10 years. More than 10 years after the onset, one patient eventually achieved FR, and one patient died. Seven patients were rehospitalized and two died due to suicide during the entire follow up. On multivariate analysis, family disorders/problems rating score was a significant predictor of PR and FR. CONCLUSIONS: This study included hospitalized ANR children aged ≤15 years, the youngest cohort ever reported. Long-term prognosis is generally favorable, but the mortality rate was 5%. Careful long-term follow up >10 years is needed to evaluate outcome of childhood-onset ANR, and family therapy is important in high-risk patients with family disorders/problems.
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Anorexia Nervosa/diagnóstico , Hospitalização , Adolescente , Anorexia Nervosa/mortalidade , Anorexia Nervosa/terapia , Criança , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Readmissão do Paciente/estatística & dados numéricos , Prognóstico , Modelos de Riscos Proporcionais , Psicoterapia , Recidiva , Indução de Remissão , Estudos Retrospectivos , Suicídio/estatística & dados numéricos , Adulto JovemRESUMO
Neurogenic pulmonary edema (NPE) is a clinical entity that can occur following central nervous system disorders. However, NPE occurs quite rarely in early childhood, and there has only been one report about pediatric NPE associated with febrile seizures. Two cases are reported here. One case involved a 2-year-old girl who presented with febrile seizures, which rapidly progressed to severe NPE. Since the NPE occurred in the emergency department room, the patient was able to be resuscitated via immediate endotracheal intubation. The other case involved an 11-month-old boy who developed respiratory distress following a 50-min episode of febrile status epilepticus. Both patients required respiratory management in the intensive care unit. However their conditions were dramatically improved within several days and fully recovered without any sequelae.
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There have been few coherent reports on extraintestinal infection or bacteremia caused by Campylobacter jejuni (C. jejuni) or C. coli in Japan. To clarify the clinical and microbiological characteristics of invasive infections caused by these two species, we retrospectively analyzed the records of patients from whom these pathogens had been isolated from sterile sites between 2000 and 2015. During this study period, we identified 9 patients. The clinical syndrome of all of these patients was bacteremia. Three patients had underlying diseases with both liver cirrhosis and malignant neoplasm, and all of these patients were aged 60 years or older. The remaining 6 patients were immunocompetent and younger than 40 years of age. All 9 patients had a fever of 38.5 degrees C or higher. The proportion of patients with gastrointestinal symptoms was lower for the 3 patients with underlying diseases, compared with the 6 patients without underlying diseases (1/3 cases vs, 4/6 cases). Of the 8 strains evaluated for antimicrobial susceptibility, all were susceptible to imipenem/cilastatin, kanamycin and erythromycin, and 2 were resistant to levofloxacin. Antimicrobial treatment was administered to 8 patients, but one spontaneously recovered without any treatment. We were able to follow the outcomes of 8 patients, and all of these patients completely recovered without relapses. We also reviewed 14 Japanese patients reported in the Japanese and English literature and found similar clinical features consisting of a high-grade fever and an association with underlying diseases and gastrointestinal symptoms. Of note, 3 agammaglobulinemic patients presented with bacteremia and extraintestinal infections and had multiple relapses. Based on the findings of our 9 cases and previous reports, the affected patients were divided into two groups according to clinical syndrome and therapeutic intervention. One group consisted of previously healthy children or young adults showing bacteremia. Most of them had enterocolitis complications but had a good prognosis. The other group consisted of patients with underlying diseases or elderly patients who presented with bacteremia alone or bacteremia with extraintestinal infections. The latter group, especially among those with humoral immunodeficiency, should be parentally treated with antimicrobial agents and requires careful monitoring for relapse. This is the largest case series study to examine invasive C. jejuni/coli infections in Japan, and it provides important epidemiological information on this rare infection.
Assuntos
Antibacterianos/uso terapêutico , Bacteriemia/microbiologia , Infecções por Campylobacter/tratamento farmacológico , Campylobacter jejuni/isolamento & purificação , Cilastatina/uso terapêutico , Imipenem/uso terapêutico , Adulto , Infecções por Campylobacter/diagnóstico , Criança , Pré-Escolar , Combinação Imipenem e Cilastatina , Combinação de Medicamentos , Feminino , Humanos , Japão , Masculino , Testes de Sensibilidade Microbiana/métodos , Pessoa de Meia-Idade , Adulto JovemRESUMO
Little is known about the clinical characteristics of invasive infections caused by nontyphoidal Salmonella sp. in childhood and the temporal changes of their incidence over a long period of time. In order to clarify these issues, we retrospectively analyzed the records of 17 such infected children admitted between August 1994 and December 2014 to our center. We divided the study period into the first (1994-1999), second (2000-2004), third (2005-2009), and fourth (2010-2014) periods. The ages of the 17 patients ranged from 2 days to 13 years. Clinical syndrome included bacteremia with enteritis (n = 13), followed by bacteremia or sepsis alone, (n = 2), osteomyelitis (n = 1), and meningitis (n = 1). The affected patient numbers in the first to fourth periods were 10, 5, 2, and 0, respectively, and the decreasing trend was significant (trend p < 0.001). This significant trend held up even after correction by the number of in-patients during each quarter period (trend p = 0.009). In the 14 cases of bacteremia with or without enteritis, excluding two neonatal cases and one case of osteomyelitis, most patients (n = 13, 93%) had WBC of <15,000/µL with a wide range of serum CRP levels (0.8-20.4mg/dL) on admission. Thus, it was very difficult to diagnose these bacteremia cases based on blood tests alone, and we needed to consider such risk factors of bacteremia as high fever, poor general condition, and younger age. O group serotypes of the isolates were as follows: O9 (n = 11), O7 (n = 5), and O4 (n = 1). Of the 15 strains evaluated, two strains were resistant to ampicillin and one each was resistant and intermediately resistant to fosfomycin. All strains were susceptible to cefotaxime, ofloxacin or levofloxacin, and trimethoprim-sulfamethoxazole. We were also presented with two rare cases : one involved sepsis due to vertical transmission and the other involved meningitis. The latter case had clinical relevance in that recurrence developed 3 weeks after treatment with susceptible antibiotics. In conclusion, this study is the first report on invasive infections caused by nontyphoidal Salmonella sp. in childhood in Japan, and provides important information on their clinical features and incidence trends over the last 20 years.