背景 神经母细胞瘤(NB)是最常见的儿童颅外实体肿瘤,临床表现及预后差异较大.目的 探讨非高危NB患儿不同预后病理分型的临床特点和预后.设计 回顾性队列研究.方法 回顾性纳入 2007 年 3 月至 2020 年 12 月首都医科大学附属北京儿童医院肿瘤内科病房收治的初诊非高危NB患儿,根据INPC分类系统分为预后良好(FH)组和预后不良(UH)组,分析不同预后病理分型的临床特点和预后.生存分析采用Kaplan-Meier方法.主要结局指标 3 年和 5年总体生存率(OS)和无事件生存率(EFS).结果 445 例患儿纳入分析,FH组 313 例,＜18 月龄 164 例(52.4％),原发部位以纵隔最多见(52.7％),远处转移 52 例(16.6％);UH组 132 例,＜18 月龄 25 例(18.9％),原发部位以腹膜后最多见(49.2％),远处转移 10 例(7.6％).两组年龄分布、原发瘤灶部位和远处转移发生率差异均有统计学意义,性别、瘤灶最大直径和LDH水平差异均无统计学意义.中位随访时间 34(0.16～166)月.FH组和UH组 3 年EFS分别为 96.4％和 92％,5 年EFS分别为 95.4％和 87.8％,差异均有统计学意义(χ2分别为 1.63 和 4.75,P分别为 0.046 和 0.029).FH组和UH组3 年OS分别为 98.3％和 98.4％,5 年OS分别为 98％和 98.4％,差异无统计学意义(χ2分别为 0.76 和 0.54,P分别为 1.53 和0.82).结论 非高危NB患儿中,UH患儿较FH患儿发病年龄更大、原发瘤灶更多位于腹膜后、远处转移发生率更低.FH患儿较UH患儿有着更好的EFS,可考虑减轻化疗强度.

Objective:To analyze the clinical characteristics and prognostic factors of high-risk neuroblastoma (HR-NB) patients with skeletal metastasis.Methods:The clinical features of 336 newly treated HR-NB patients with skeletal metastases admitted to the Department of Medical Oncology of Beijing Children′s Hospital, Capital Medical University from January 2007 to December 2018 were analyzed retrospectively.Kaplan-Meier method was used for the survival analysis, and Log- Rank test was used for univariate prognosis analysis.The Cox model was used to analyze the multifactorial prognostic analysis. Results:A total of 336 HR-NB patients were recruited, involving 188 males and 148 females with the median age of onset of at 43 (4-148) months.Skeletal metastases affected the viscerocranium (89 cases, 26.5%), neurocranium (193 cases, 57.4%), vertebrae (298 cases, 88.7%), sternum and ribs (183 cases, 54.5%), pelvis (270 cases, 80.4%), upper limbs (182 cases, 54.2%) and lower limbs (240 cases, 71.4%). The 5-year event-free survival (EFS) rate and overall survival (OS) rate were (30.4±2.7)% and (41.3±2.9)%, respectively.Univariate analysis showed a significantly lower 5-year OS rate in skeletal metastatic HR-NB patients with poor prognostic classification, the morphology of neuroblastoma (stroma-poor) and ganglioneuroblastoma (intermixed), high index of mitosis-karyorrhexis index, lactate dehydrogenase≥587 U/L, serum ferritin≥92 μg/L, MYCN amplification and 1p loss of heterozygosity, and metastases in the viscerocranium, neurocranium, vertebrae, sternum and ribs, pelvis, upper limbs and lower limbs (all P<0.05). The 5-year OS rate of HR-NB patients with all 7 regions of skeletal metastases was only (14.2±5.9)%, which was significantly lower than that in patients with a single region metastasis or multi-region metastases[(66.0±10.2)% vs.(43.6±3.4)%, χ2=45.722, P<0.05]. Cox multifactorial analysis showed that MYCN amplification ( HR=4.165, 95% CI: 2.356-7.363) and the viscerocranium metastasis ( HR=2.560, 95% CI: 1.519-4.315) were the independent risk factors affecting the prognosis of HR-NB patients with skeletal metastases (all P<0.05). Conclusions:The prognosis is extremely poor in HR-NB patients with multiple skeletal metastases at the initial diagnosis.The amplification of MYCN and the viscerocranium metastasis are the poor prognostic factors for HR-NB patients with skeletal metastases.

目的 总结伴MYCN扩增的婴儿神经母细胞瘤(NB)临床特征及预后分析.方法 回顾性分析2010年1月1日-2021年12月31日在我院诊断并规律治疗的年龄≤12个月,同时伴有MYCN扩增的13例婴儿NB的临床资料,总结临床特征及评估预后,并以13例MYCN无扩增的婴儿NB做对照,随访截止2022年4月30日.结果(1)MYCN基因扩增的婴儿NB占同期本单位收治婴儿NB总数的5.5％(13/235),中位诊断年龄9(4～12)个月,中位随访时间28个月(13天～130个月).(2)13例MYCN基因扩增的婴儿NB均为高危,Ⅳ期11例,Ⅲ期1例;12例肿瘤原发部位为腹膜后/肾上腺,1例为纵膈;12例发生肿瘤转移,其中10例远处骨转移、9例骨髓转移、7例肝脏转移;11例接受手术治疗,其中3例化疗前行手术治疗,8例化疗后行手术治疗,2例仅化疗,平均化疗9.6个疗程;6例放疗,中位放疗剂量为20.1Gy;3例行自体造血干细胞移植治疗;11例手术治疗患儿中,6例瘤灶完整切除,4例部分切除,1例不详;5例无事件生存,8例事件发生的中位时间为17(0.2～88)个月,6例出现肿瘤复发或进展,其中5例化疗结束后复发,复发中位时间5(2～58)个月,1例在化疗中疾病进展,13例中7例死亡.(3)单因素分析显示LDH、NSE水平显著增高的MYCN扩增NB婴儿预后不良(P＜0.05);MYCN扩增组与MYCN无扩增组的预计5年无事件生存率(EFS)分别为21％和100％,具有显著性差异(P=0.0004),预计5年总生存率(OS)分别为33％和100％,具有显著差异(P=0.002);MYCN扩增组发生骨转移、骨髓转移、肝转移及LDH≥1500的比例显著较高(P＜0.05).结论 伴MYCN扩增的婴儿NB预后明显不良,且LDH、NSE水平显著增高者预后更差.

目的 通过收集中青年晕厥患者的临床资料,分析其临床特点,以期提高对18～60岁晕厥患者的临床理解和认识.方法 对2018年5月至2020年10月就诊北京天坛医院诊断为"晕厥"的青年、中年患者132例开展回顾性研究,按照年龄35、45岁为临界值把患者群体分为青年组(18～35岁)、青壮年组(36～45岁)、中年组(46～60岁),收集患者一般资料,临床及实验室检查结果、1个月内的预后转归等信息.采用单因素方差分析、非参数检验等统计学方法探讨患者晕厥发作及发生短期不良事件的特点,并详细解析典型病例.结果 中青年晕厥患者中神经介导性晕厥比例最高(80.30％),发生短期不良事件比例较低(27.36％),神经介导性晕厥的起始病因存在差异,与患者合并的基础疾病密切相关.心源性晕厥发生短期不良事件比例最高(61.11％),患者就诊时收缩压、末梢血氧饱和度、B型钠尿肽水平、血肌酐水平在短期不良事件发生与否的两组患者中存在显著差异(P<0.05).结论 中青年患者的晕厥发作虽然良性病因居多,但可能的严重病因在临床诊疗中不容忽略,要尽力查找原因及合并症,控制晕厥反复,避免不良事件发生.

Background The aim of this study was to summarize the clinical characteristics, therapeutic effects and prognosis of patients with rhabdomyosarcoma (RMS) and bone marrow metastasis, improve the understanding of this disease. Method This was a single-institution retrospective study involving the children with RMS, who presented with bone marrow metastasis at initial presentation to our hospital between 1st, Jan, 2006 and 31st, Dec,2019. Follow-up concluded on 31st, Dec, 2020 and the clinical data were collected and analysed. Result Between 1st Jan 2006 and 31st Dec 2019, 13 eligible patients presented to our hospital, including 10 males and 3 females, these eligible patients accounted for 4.5% of all RMS patients. The median age at onset was 5.6 years (range 1.7-14 years). The patients not only had unfavourable primary sites, but also had multiple metastases. The bone marrow aspirate samples of the patients comprised 8-95% blast-like cells. Nine of 13 patients were misdiagnosed with haematological malignancies or other solid tumours. With respect to histology, four of 13 children were classified as embryonal RMS and nine as alveolar RMS. Eleven patients underwent PAX-FOXO1 fusion testing; eight had the POX- FOXO1 fusion gene. Immunohistochemically(IHC) analysis revealed that the tumour cells were positive for Desmin, Vimentin, Myo-D1 and Myogenin. More importantly, the patients had extremely poor prognoses, the median EFS was 12.0 months (range 3-28.3 months) and the median OS was 27.0 months (range6-46.2 months). Conclusion This study demonstrates that children with RMS and bone marrow metastasis usually exhibit atypical primary sites and multiple metastases, with presentation mimicking haematological malignancies or other solid tumors at initial presentation. Pathology and IHC analysis combined with POX-FOXO1 fusion gene detections can effectively confirm the diagnosis. These patients are more likely to relapse or progress during early treatment and are prone to intracranial metastasis. While multidisciplinary therapy combined with Temozolomide may prevent it, further prospective research is required to evaluate the therapeutic effects.

Objective:To summarize the causes of death and severe complication in the early diagnosis of children with neuroblastoma (NB), and to analyze the relative factors of early death of children with NB, so as to raise awareness and reduce early mortality by early detection and early intervention.Methods:Patients with newly diagnosed NB in the Hematology Oncology Center of Beijing Children′s Hospital from April 2007 to December 2017 were included consecutively, and those died within 1 month after diagnosis were retrospectively analyzed.The general data of patients, immediate causes of death, complications, time elapsed between death and diagnosis, whether to receive chemotherapy and other information were collected.Results:A total of 654 cases were included for diagnosis, treatment and follow-up, 31 cases of which died in early stage, accounting for 4.7% of the total.The major complication were pulmonary infection in 18 cases (58.1%) and bone marrow suppression after chemotherapy in 17 cases (54.8%), tumor rupture hemorrhage in 16 cases (51.6%), multiple organ failure in 8 cases (25.8%). Risk factor analysis of the 31 early death cases with NB was conducted.Single factor analysis: there were statistical differences between early death group and non-early death group in risk grouping ( P=0.006 6), bone marrow invasion ( P=0.020 7), site of primary tumor ( P=0.016 7), age ( P=0.003 3), lactate dehydrogenase (LDH) level ( P<0.000 1), neuron-specific enolase (NSE) level ( P<0.000 1), serum ferritin level ( P=0.016 0), D dimer level ( P<0.000 1), fibrinogen level ( P=0.002 7), diameter of tumor ( P<0.000 1), hemoglobin ( P<0.000 1), platelet level ( P<0.000 1), serum albumin level ( P<0.000 1). Multiple-factor analysis: age younger than 30 months, OR=2.824 (95% CI: 1.084-7.359), LDH level greater than 1 004 IU/L, OR=6.991 (95% CI: 2.135-22.887), albumin level less than 36 g/L, OR= 65.237 (95% CI: 2.024-13.545), hemoglobin level less than 92 g/L, OR=5.358 (95% CI: 2.024-13.545), platelet level less than 192×10 9/L, OR=3.554 (95% CI: 1.267-9.965). Conclusions:Strengthening vital signs detection after admission, identifying severe life-threatening complications such as rupture of tumors as early as possible, implementing symptomatic interventions such as appropriate sedation and active transfusion of blood products as early as possible after invasive operation, and transferring to intensive care unit for respiratory support when necessary are important means to avoid early death.

Abstract Paired-like homeobox 2B (PHOX2B) is a highly sensitive and specific biomarker for diagnosing neuroblastoma, as well as detecting minimal residual disease in neuroblastoma. The clinical significance of PHOX2B expression in bone marrow (BM) and peripheral blood (PB) samples of newly diagnosed patients with very low-, low- and intermediate-risk neuroblastoma remains unknown, to the best of our knowledge. The expression level of PHOX2B in paired BM and PB samples of patients with newly diagnosed neuroblastoma was validated using reverse transcription-quantitative polymerase chain reaction (RTqPCR). Among the 132 patients, 26 exhibited a positive PHOX2B expression BM (19.7%) and 11 in PB (8.3%) samples. PHOX2B was highly expressed in BM and PB samples from patients aged <18 months, with International Neuroblastoma Risk Group Staging System stages M and MS, 1p loss of heterozygosity, and high levels of lactate dehydrogenase, serum ferritin and neuron-specific enolase (p < 0.05). In all eligible patients, the 2-year event-free survival (EFS) and overall survival (OS) rates were 94.7 ± 2.0% and 97.7 ± 1.3%, respectively. However, the 2-year EFS rates were significantly decreased to 76.9 ± 8.3% and 63.6 ± 14.5% in patients with a positive PHOX2B expression in BM and PB samples, respectively (p < 0.05). Similarly, the 2-year OS rates were also decreased to 88.5 ± 6.3% and 81.8 ± 11.6% in patients with a positive PHOX2B expression in BM and PB samples, respectively (p < 0.05). In conclusion, a positive PHOX2B expression in BM and PB samples at diagnosis had a strong adverse prognostic effect on patients with non-high-risk neuroblastoma.

目的 总结神经母细胞瘤(NB)患儿应用铂类药物化疗后毒性反应和药物基因多态性检测结果,探索二者之间的关联性,为指导临床个体化治疗提供依据.方法 连续纳入2016年2月1日-2017年5月31日期间,北京儿童医院血液肿瘤中心确诊并系统治疗的NB患儿.依据BCH-NB-2007危险度分组标准,分为低危、中危、高危组,接受含顺铂或卡铂方案化疗.化疗前留取外周血,采用荧光杂交方法对两种铂类化疗药物基因组DNA进行检测,化疗后记录患儿各系统毒副反应,并按国立癌症研究所常规毒性标准(NCI-CTCAE 5.0中文版)进行分级.进一步将3/4级毒性反应与药物基因检测结果进行关联性分析.结果 共纳入98例NB患儿,男50例,女48例.中位年龄为46(5 ～115)个月.中低危组单用卡铂者36例(36.7％).高危组62例(63.3％),其中单用顺铂者46例,顺铂+卡铂者16例.所有NB患儿在病初时留取血标本检测GSTP1基因多态性,AA型61例(62.2％),AG型33例(33.7％),GG型4例(4.1％);部分患儿(51例)还进行了XPC基因多态性的检测,其中GG型8例(15.7％),GT型24例(47.1％),TT型19例(37.3％).所有NB患儿中,出现3/4级毒性反应共61例(62.2％),其中以3/4级血液毒性最为常见(55例,56.1％);3/4级恶心呕吐、肝损害及电解质紊乱各2例,共占6％.分析3/4级毒副反应与所检测的两种药物基因多态性之间的相关性,GSTP1基因多态性与3/4级毒性反应相关,组间差异具有显著性,AA型毒副反应重于AG型和GG型(P＜0.05);XPC基因多态性与3/4级毒性反应相关性差异无显著性.结论 NB患儿应用铂类化疗毒性反应以血液系统毒性、消化道毒性为主,GSTP1基因多态性与3/4级毒性反应相关,AA型毒副反应最重;XPC基因多态性与3/4级毒性反应无相关性,有待扩大样本量加以验证.

Introduction: Metastatic neuroblastoma (NB) is an aggressive malignancy with a poor prognosis. Many patients present with relapsed high-risk NB after undergoing first-line treatment, and there is no standard therapy available in this setting. Patient concerns: The present study aimed to present the cases of 2 patients with recurrent high-risk NB. Diagnosis: Two children with International Neuroblastoma Stage System stage 4 high-risk NB chemotherapy. The disease recurrent after finishing the treatment. Interventions: Both patients (34 months old and 41 months old) experienced recurrence, received second-line treatment, and then received maintenance treatment using apatinib plus retinoic acid. The apatinib (10 mg/kg per day) and retinoic acid (160 mg/m(2)per day) were administered on alternating 2-week cycles, which was continued for 1 year. Outcomes: The 2 patients had achieved complete response by the 1-year follow-up after starting apatinib plus retinoic acid, and did not experience any adverse drug reactions. Conclusion: The outcomes from these cases suggest that apatinib plus isotretinoin might be an option for maintenance therapy in patients with recurrent high-risk NB.

Objective:To improve the awareness of neuroblastoma (NB) with cervical lymph node metastasis in children patients by summarizing the clinical features of such patients and analyzing their survival situation.Methods:The research analyzed the medical records of 225 patients with cervical lymph node metastasis of NB from April 1, 2007 to May 31, 2017 in Beijing Children′s Hospital, Capital Medical University.The treatment were divided into 2 phases according to treatment time (one from April 1, 2007 to December 31, 2011 and the other from January 1, 2012 to May 31, 2017). The survival situation and treatment effect in each phase were analyzed.The following up time ended at Jan 1, 2018.Results:(1)Clinical features: total 225 cases admitted in the research with about 37.3% of all the NB patients.One hundred girls(44.4%) and 125 boys(55.6%). The age from 2 months to 147 months, the me-dian age of patients was 37 months.The age under 18 months were 27 cases(12.1%). The majority primary site of tumor was located in retroperitoneal(174 cases, 77.3%) and mediastinum(48 cases, 21.3%). There were 33 cases which metastasic site confined to cervical lymph node(4N stage, 14.7%); 139 cases (62.1%) with bone marrow metastasis, 159 cases (71.0%) with bone metastasis.The number of patients in high-risk group was 208 cases(91.2%), while the low-risk and the medium-risk group was 17 cases(7.5%). (2)Treatment effect and survival analysis: a total of 200 cases received systemic treatment and followed-up in our hospital.The follow up time from 2 months to 123 months, the median follow up time was 23 months.The 3 year overall survival (OS) rate of all the patients was 56.4%, the 3 year event free survival (EFS) rate was 52.0%.While the 5-year OS was 46.5%, and the 5-year EFS was 39.7%.According to the first phase of treatment(April 1, 2007 to December 31, 2011), the 3-year EFS was 49.6%, and the 3-year OS was 54.4%, the 5-year EFS was 39.5%, and the 5-year OS was 44.7%.According to the second phase of treatment(January 1, 2012 to May 31, 2017), the 3-year EFS was 58.1%, and the 3-year OS was 57.3%.The 5-year EFS was 48.7%, and the 5-year OS was 46.8%.About the 4N patients, the 3-year EFS was 71.2%, and the 3-year OS was 82.2%.The 5-year EFS was 61.5%, and the 5-year OS was 76.7%.Conclusions:Cervical lymph node is one of the most common distant metastasis of NB.More than half of the patient with bone or bone marrow metastasis.The prognosis of patients′ metastatic disease limited to cervical lymph nodes(4N stage), but still worse than the foreigner haver reported.The probable reason is the proportion of high-risk patients in the center is higher than the foreign research.

Objective To analyze the clinical characteristics of children with neuroblastoma (NB) complicated with lung or pleural metastasis,further to explore the correlation between characteristics and short-term outcome of NB,so as to provide a basis for clinical diagnosis and treatment.Methods A retrospective analysis was performed concerning the age of onset,clinical features,treatment and outcome of 36 patients with NB who were admitted at Blood Tumor Center,Beijing Children's Hospital of Capital Medical University from December 2007 to December 2017.The diagnostic criteria,therapeutic regimen and therapeutic efficacy criteria of the enrolled children were all based on the NB protocol of Beijing Children's Hospital of Capital Medical University (BCH-NB-2007),the clinical stage was based on international clinical stage of neuroblastoma (INSS stage),and stratified treatment was conducted according to the BCH-NB risk grouping standard.The follow-up period lasted till October 31,2018.Results (1) The common clinical features of grouped children:36 patients were selected into the group,accounted for 5.99％ (36/601 cases) in total hospitalized NB children,they were less than 10 years old,10 cases under 18 months,and the median age was 29.5 months (9-105 months);20 cases were male,and 16 cases were female;the primary tumor was located in the retroperitoneal site in 19 cases,accounting for 52.78％,9 cases in adrenal site,accounting for 25.00％,and 8 cases in mediastinal site,accounting for 22.22％.Risk groups:29 cases were in high-risk group,6 cases were in medium-risk group and 1 case was in low-risk group.The main symptoms were of pain onset in 8 cases,fever in 6 cases,local mass in 6 cases,abdominal mass in 4 cases,mediastinal mass in 3 cases,paleness in 3 cases,subcutaneous nodules in 2 cases,abdominal distension in 2 cases,lower limb swelling in 1 case,and diarrhea in 1 case.Among them,16 cases had respiratory system symptoms first,accounting for 44.4％.(2) Laboratory examination:there were 35 patients of neuron-specific enolase (NSE) ≥25 μg/L on the initial diagnosis,of which 11 cases were more than 370 μg/L,the value of serum lactate dehydrogenase (LDH) ≥ 717.5 U/L in 25 patients,accounting for 69.44％,and 10 cases were accompanied by N-myc gene amplification.(3) Imaging examination:on the first diagnosis,chest/abdomen CT showed 75.75％ (24/33 cases) of pleural or lung involvement,PET-CT showed 81.8％ (27/33 cases) of pleural or lung involvement,B-ultrasound showed 41.67 ％ (5/12 cases) of pleural or lung involvement;3 imaging examinations showed:1 positive in 16 cases,2 positive in 16 cases,and 3 positive in 4 cases.(4)Comparison of clinical features of pleural and pulmonary involvement:among the 30 children with pleural involvement,6 cases had respiratory symptoms,3 cases had respiratory symptoms on the 6 cases with pulmonary involvement only,and 4 cases with pleural and pulmonary involvement had no respiratory symptoms at first diagnosis.(5)Treatment and outcome:2 cases died because of critical condition after diagnosis,5 cases didn't receive the law treatment,29 cases accepted law stratification treatment,among them,1 case in low risk group,INSS-Ⅳ,alleviate current (CR);4 cases in the moderate group,INSS-Ⅳ,CR in 2 cases,partial response (PR) in 1 case,progress in 1 case,new tumor foci occurring after chemotherapy discontinuation for 13 months.Twenty-four cases were in the high-risk group,event occurred in 7 cases (29.17％) of them,1 case had progression by postoperative evaluation,4 cases of progression at 1.5,2.0,3.0 and 6.0 months after cessation of chemotherapy,and 2 cases had recurrence at 11 and 17 months after cessation of chemotherapy.Overall survival rate (OS) was 41.4％ for all children analyzed by Kaplan-Merier,and 32.9％ of them were predicted to have 3-year event-free survival.Conclusions Children with pulmonary or pleural metastasis of neuroblastoma have no specific respiratory symptoms.CT scan might be a useful method for diagnosing the group Ⅳ children with pulmonary or pleural metastasis of neuroblastoma.Moreover,there seemed to be no significant correlation between the N-myc gene expression and survival prognosis of these children.

Abstract Background To improve cure rates for neuroblastoma (NB), it is important and necessary to evaluate therapy response. Our investigation focuses on using plasma cell free DNA (cfDNA) as a biomarker to determine tumor burden and minimal residual disease (MRD) of NB patients during chemotherapy. Methods Total 58 NB patients were recruited from July 2016 to December 2017. Therapy regime and risk classification were based on COG standard and BCH‐NB‐2007 protocol. RECIST study was used to judge response to therapy at the end of fourth cycle of chemotherapy (CC4) and maintenance stage (MS) respectively. Serial quantifications of cfDNA, NSE, and LDH were examined at four stages, including newly diagnosed, second and CC4, and maintenance. Results During early chemotherapy, 65.5% of NB kids responded well. Consistently, cfDNA, NSE, and LDH levels were down‐regulated in NB patients with partial remission (PR) compared to those with stable disease (SD). In both training and predicting sets, the levels of cfDNA were significantly comparable between PR and SD only at CC4 stage. To predict the insufficient response to early chemotherapy, the optimal AUC value of cfDNA was 0.732 and 0.747 in training and predicting sets respectively, with a sensitivity of 63.2% and 80% specificity at 11.59 ng/ml and a sensitivity of 68.4% and 90% specificity at 10.35 ng/ml. At MS, responded NB patients were slightly increased up to 70%. This evaluation was confirmed by further decrease in cfDNA and NSE levels during intermediate chemotherapy in comparison with early stage. Conclusion The dynamic change of cfDNA was considered as a surrogate biomarker to evaluate tumor burden and MRD of NB during early and intermediate therapy periods.

Objective: To analyze the clinical characteristics of newly treated high-risk group neuroblastoma (NB) patients with bone marrow metastasis and to explore the prognostic factors. Methods: The clinical features (sex, age, stage, risk group, pathological type, metastatic site, etc.) of 203 newly treated high-risk NB patients with bone marrow metastasis admitted to Hematology Oncology Center, Beijing Children's Hospital from January 2007 to December 2016 were analyzed retrospectively. There were 118 males (58.1%) and 85 females (41.9%). Kaplan-Meier method was used for survival analysis and Cox regression was used to analyze the prognostic factors. Results: The age at onset of the 203 patients was 41 months (9-147 months). The metastatic sites at diagnosis were as follows: bone in 195 cases (96.1%), distant lymph nodes in 104 cases (51.2%), skull and endomeninx in 61 cases (30.0%), orbit in 30 cases (14.8%), pleura in 16 cases (7.9%), liver in 13 cases(6.4%), canalis spinalis in 13 cases (6.4%), other sites in 11 cases (5.4%) and skin and soft tissue in 10 cases (4.9%). In all, 194 cases were enrolled for prognostic analysis. The follow-up time was 36 months (1 day-138 months) , and the 5-years event free survival (EFS) and overall survival (OS) were 36.1% and 39.7%, respectively. A total of 118 patients (60.8%) had events (first relapse or death) with the time to event occurrence was 15 months (1 day-72 months), whereas 112 patients (57.7%) died with the event occurrence to death time was 3 months (1 day-21 months). There was no significant difference in 5-years OS between radiotherapy group and non-radiotherapy group (42.3% vs. 38.3%, χ(2)=3.671, P=0.055). The 5-years OS in transplantation group was significantly better than the non-transplantation group (44.3% vs. 35.5%, χ(2)=8.878, P=0.003), and the radiotherapy combined transplantation group also had a better 5-years OS rate than the non-radiotherapy combined transplantation group (45.8% vs. 37.3%, χ(2)=5.945, P=0.015). Univariate survival analysis showed lactate dehydrogenase ≥ 1 500 U/L, the amplification of MYCN, the metastatic sites of orbit, canalis spinalis and pleura were associated with poor prognosis of newly diagnosed high-risk NB patients (χ(2)=21.064, 13.601, 3.998, 6.183, 15.307, all P<0.05). The amplification of MYCN and the metastatic sites of pleura were risk factors for prognosis of newly diagnosed high-risk NB patients by Cox regression models (HR=1.896,1.100, 95%CI: 1.113-3.231, 1.020-1.187, both P<0.05). Conclusions: The prognosis is unfavorable in high-risk group NB patients with BM metastasis. Radiotherapy combined with transplantation can further improve the prognosis of these patients. The amplification of MYCN and the metastatic sites of pleura were the poor prognostic factors for high-risk NB patients with bone marrow metastasis.

目的 总结首都医科大学附属北京儿童医院血液肿瘤中心近10年诊治的肝母细胞瘤(hepatoblastoma,HB)患儿临床特点和治疗效果,结合随访资料,为探讨HB的合理诊疗策略,减少不良反应,提高患儿的无事件生存率提供依据.方法 分析2009年2月至2018年5月,在首都医科大学附属北京儿童医院新诊断的、规律诊治,并坚持长期随访的HB患儿.采用以手术治疗、化学药物治疗和放射治疗的多学科联合诊治方案.化学药物治疗方案采用A方案(顺铂+长春新碱+氟尿嘧啶)以及B方案(顺铂+阿霉素)的联合化学药物治疗方案.记录患儿年龄、性别、病程、病初血清甲胎蛋白(alpha fetal protein,AFP)、临床分期、病理类型、治疗方法和治疗效果,随访至2018年11月30日.结果 共收治51例患儿,其中6例患儿因在笔者医院治疗时间短、回当地治疗未纳入临床总结中;3例患儿治疗前因肿瘤破裂出血等合并症死亡.余42例接受系统治疗并随访.中位年龄19(2 ～102)个月.临床分期:Ⅱ期1例,Ⅲ期34例,Ⅳ期7例.病初血清AFP:31.6 ～2 200 000 μg/L(中位数192 274.5 μg/L).39例患儿中位随访时间36(6～ 115)个月.5年无事件生存率为74.72％.患儿化学药物治疗后全血细胞计数下降不明显,化学药物治疗期间无严重感染发生.化学药物治疗期间无明确心脏毒性指征.仅1例患儿出现短期听力受损.结论 手术联合化学药物治疗是HB的主要治疗手段,现行方案中阿霉素和顺铂剂量患儿耐受性好,5年无事件生存率较高,临床需要密切随访这些患儿的远期预后.

目的 总结和分析伴有骨转移的神经母细胞瘤(NB)患儿的初诊时细胞因子水平,为进一步寻求更为有效的治疗,改善生存率提供依据.方法 选择自2011年12月1日-2017年4月30日期间,于首都医科大学附属北京儿童医院血液肿瘤病房确诊的伴有骨转移NB患儿作为研究组,无骨转移患儿作为对照组.诊断、分期等根据北京儿童医院-2007-NB方案.测定每例患儿病初外周血细胞因子水平:干扰素-γ(IFN-γ),肿瘤坏死因子-α(TNF-α)表达水平.回顾性分析不同临床特征NB患儿病初在细胞因子水平上有无差异.结果 216例伴有骨转移NB患儿中,男女比例约为1.6:1,中位年龄37.5个月.初诊时IFN-γ骨转移组较无骨转移组降低;TNF-α骨转移组较无骨转移组升高(P＜0.05).有发热或骨痛组患儿较无发热或无骨痛组患儿TNF-α水平升高(P值均为0.00).此外,初诊时骨转移组患儿同时存在骨髓转移者较无骨髓转移患儿IFN-γ降低,TNF-α升高(P＜0.01).结论 外周血细胞因子水平,特别是TNF-α及IFN-γ,可以间接反映NB患儿骨转移情况.测定TNF-α及IFN-γ的表达水平在一定程度上可作为评估和监测有无骨骼转移辅助手段.

Objective To summarize the clinical features of neuroblastoma (NB)with N - myc gene amplifi-cation in order to analyze tumor shrinkage and bone marrow remission in the early stage of chemotherapy,and to eva-luate the children's initial sensitivity to chemotherapy. Methods The medical records of 38 patients with N - myc am-plification of NB were reviewed (bone marrow or tumor tissues were positive during fluorescence in situ hybridization probe),who were treated between February 2012 to December 2016 at the Hematology Oncology Center,Beijing Chil-dren's Hospital,Capital Medical University. The regimens included chemotherapy,surgery,stem cell transplantation, radiotherapy,and maintenance treatment. The data were reviewed for the medical history. The variations of biomarker, bone marrow cells and the primary site were analyzed before and after 2 courses of CAV (Cyclophosphamide + Adriamy-cin + Vincristine)regimen chemotherapy,in order to observe the short - term effect of chemotherapy and the results were described with statistics. Results Total 38 cases were studied,22 boys(58. 9％)and 16 girls(42. 1％). The median age was 30 months. The primary sites of 37 cases of tumor were located in the retroperitoneal and adrenal area,1 case located in the posterior mediastinum. Bone marrow cytology was negative in 12 cases of them,but bone marrow biopsy suggested bone marrow metastasis,while bone marrow cytomorpholigic examinations were positive in the other 26 cases. Of all the 37 cases the lactate dehydrogenase (LDH)levels were reported higher than the normal value. LDH level was under 500 U/ L in one case,9 cases above 4000 U/ L. The neuron specific enolase (NSE)level of all the cases was higher than the normal and NSE level in 36 cases was higher than 100 μg/ L. In one patient the diameter of tumor was less than 5 cm,lager than 10 cm in 32 cases. The lesion of 33 tumor cases before chemotherapy by enhanced CT was ≤100 cm3 in 12 cases,> 100 - 500 cm3 in 11 cases,among which 6 cases ranged from 500 - 1000 cm3 ,4 cases larger than 1000 cm3 . All the 38 cases received 2 courses of chemotherapy. LDH levels of 4 cases became normal,and LDH levels fell under 500 U/ L in 18 cases,while LDH levels of the other 3 cases were above 1000 U/ L. Among 38 cases, the NSE level in 6 cases was reduced to normal,and 16 cases reduced to 25 - 100 μg/ L. The bone marrow examination of 36 cases reversed to negative. According to the image examination,the overall response rate after 2 courses of chemo-therapy was 84. 8％ . One case achieved very good partial remission,21 cases achieved partial response,7 cases a-chieved metastatic remission,2 cases had no remission,while 2 cases showed progression. After 2 courses of chemother-apy,the tumor diameter in 7 cases was less than 5 cm,while that of 22 cases was above 10 cm. Conclusions The ma-jority primary site of NB with N - myc gene amplification is located in retroperitoneal and adrenal area. Patients with the huge tumor have a heavy burden and the biomarker is always high at the early stage. NB with N - myc gene amplifica-tion is sensitive to chemotherapy. After 2 courses of chemotherapy,there is a sharp decrease in the level of biomarker and the tumor burden. Chemotherapy can diminish the burden of tumor in early stage. But because of the huge burden and the huge size of tumor,it's not the best time for surgery and stem cell collection. The patients should go on receiving chemotherapy for remission of disease.

IMPORTANCE:Childhood solid tumors account for the highest proportion of childhood cancers and are one of the leading causes of death in childhood. However, their pathogenesis is unclear.OBJECTIVE:To explore prenatal and perinatal risk factors for solid malignancies in children.METHODS:We enrolled 71 consecutive pediatric patients (44 boys and 27 girls; median age, 30 months) with solid tumors who were diagnosed and treated at our center from January 2013 to December 2016 as the case group. We also enrolled 211 age- and residence-matched healthy children (ratio of approximately 3:1 with the case group) as the control group. We conducted a questionnaire-based survey with the parents of these 282 children. Univariate and multivariate conditional logistic regression analyses of the collected data were performed.RESULTS:Confirmed solid malignancies included neuroblastoma (n = 32), rhabdomyosarcoma (n = 18), retinoblastoma (n = 7), renal tumors (n = 3), and other tumors (n = 11). Risk factors for solid childhood tumors in the univariate analysis were the parents' age, gravidity, parity, abortion history, vaginal bleeding, family history of malignancy, and prenatal use of folic acid or hematinics/iron supplements (P < 0.05), and those in the multivariate analysis were higher parity (odds ratio [OR], 2.482; 95% confidence interval [CI], 1.521-4.048), family history of malignancy (OR, 3.667; 95% CI, 1.679-8.009), and prenatal use of hematinics/iron supplements (OR, 2.882; 95% CI, 1.440-5.767). In contrast, use of prenatal folic acid was protective (OR, 0.334; 95% CI, 0.160-0.694).INTERPRETATION:A family history of malignancy, use of prenatal hematinics/iron supplements, and higher parity are risk factors for solid childhood tumors, whereas use of prenatal folic acid is a protective factor.

Objective To summarize the clinical data and characteristics of neuroblastoma (NB) with pancreatic infiltration and to assess the clinical features and the prognosis of NB.Methods According to NB protocol at Beijing Children's Hospital,Capital Medical University(BCH-NB-2007),based on Hong Kong NB protocol,the patients were divided into 3 groups of low-risk (LR) group,medium risk (MR) group and high-risk (HR) group.All children were followed up till March 31,2017.Diagnosis of pancreatic infiltration of NB was made by abdominal enhancement of CT,enhanced magnetic resonance imaging (MRI) or 18-fluorodeoxyglucose-positron emission tomography-computed tomography(18F-FDG-PET/CT),any of which could suggest NB pancreatic infiltration or postoperative pathology prompted NB to infiltrate the pancreas.Retrospective summary and analysis of indicators were performed,which included the initial diagnosis of primary tumor and metastatic tumor site,tumor markers,clinical stage,risk group,imaging features and treatment.Results (1) Totally 50 eligible patients were included:27 females,23 males,median age of 33 months (7-129 months),10 cases ≤ 18 months,40 cases ＞ 18 months;3 cases were of International Neuroblastoma Staging System(INSS)-Ⅲ,47 cases of INSS-Ⅳ;2 caes of LR,3 cases of MR,45 cases of HR;28 cases had a fever,27 cases with abdominal mass,14 cases with abdominal pain,9 cases with limb pain,5 cases with vomiting,4 cases with diarrhea,and 1 case with jaundice.Forty-nine cases of primary tumor were located in the retroperitoneal adrenal gland,and 1 case in the pelvic cavity.Thirty-two cases had tumor diameter≥ 10 cm.(2)Tumor markers and imaging features:the median serum lactate dehydrogenase (LDH) value in 50 cases was 669 U/L (263-6 762 U/L),of them 19 cases ＞ 1 000 U/L.A total of 80％ cases had neuron specific enolase (NSE) ＞ 0.15 ng/L.Nine cases had elevated amylase (AMY),and 7 cases had elevated lippase (LPS),and all the levels were elevated in 5 cases.A total of 41 cases had pancreas infiltration by abdominal ultrasound,44 cases had pancreas infiltration by abdominal enhancement computed tomography (CT),100％ (14/14 cases)of pancreas infiltration was confirmed by abdominal reconstruction enhancement nuclear imaging MRI,and NB pancreas infiltration was proved in 41.3％ (19/46 cases) by 18F-FDG-PET/CT.Comparison of the above 4 imaging studies:one imaging examination index was positive in 7 cases,accounting for 14.0％,2 positive in 26 cases,accounting for 52.0％,3 positive in 15 cases,accounting for 30.0％,and 4 positive in 2 cases,accounting for 4.0％.(3) Treatment outcomes:totally 50 cases received treatment,including 2 cases of LR,all cases were of INSS-Ⅲ,and 1 case with complete remission (CR).Three cases of MR belonging to INSS-Ⅳ had complete resection of the tumor,1 case had recurrence and died,and the other two were stable.Forty-five cases with HR,median follow-up lasting for 15 (4-53) months,16 cases had occurrence (35.6％),3 cases were relapsed after stopping treatment for 2,3,18 months,respectively;tumor progressed in 12 patients during treatment,and 1 case got severe intracranial infection and gave up treatment before death.Kaplan-Meier analysis showed the expected 3-year event free survival(EFS) rate was 22.1％,and 3-year overall survival(OS) rate was 38.5％.Conclusions Preliminary results show that 90％ with pancreatic infiltration of NB belong to Ⅳ HR group of children,and almost primary tumor is almost located in the retroperitoneal ragion.NB with pancreatic infiltration clinical manifestations is hidden and nonspecific.More than half of the children have no obvious abdominal pain or vomiting,and so imaging examination is needed to determine the situation of pancreatic metastasis further.Abdominal reconstruction enhancement MRI has a high sensitivity and specificity for pancreatic metastatic lesions,which can be used as the basis for early diagnosis.The overall prognosis is poor.The expected 3-year EFS rate can be 22.1％,3-year OS rate was 38.5％.

目的 总结以腹泻为首发症状的神经母细胞瘤(NB)的临床特点、腹泻症状缓解与治疗、转归情况,提高对以腹泻为主要表现NB的认识.方法 回顾性分析2015年-2017年北京儿童医院血液肿瘤中心病房收治的以腹泻为首发症状的NB患者临床特点及治疗、转归情况.结果 入组患者共11例,中位确诊年龄为18月,中低危组(7/11),高危组(4/11).肿瘤原发部位见于肾上腺区或腹膜后(9/11)及纵隔内(2/11),无骨髓或中枢转移,尿HVA、VMA中位值较正常升高约2.4～3.6倍,血清LDH、NSE中位值较正常范围升高约1.1 ～2.1倍.11例患儿中6例首先进行了手术切除肿瘤,并均在术后使腹泻得到了控制.其余5例患者先进行了术前化疗,除2例患者腹泻症状在接受化疗前自行缓解外,其余3例患者在化疗期间腹泻症状得到一定缓解,其中有1例同时应用了奥曲肽对症治疗,直到手术切除肿瘤后腹泻完全停止.所有患者化疗5～8个周期,目前中位随访时间为18个月,总体生存率及无事件生存率均为100％.结论 以腹泻为首发症状的NB确诊年龄偏小,中低危组所占比例较高,肿瘤标志物的中位水平较正常值升高不显著.手术切除肿瘤是最有效缓解腹泻症状的治疗方法.

Objective To explore the feasibility of immunotherapy intermittently with high dose intravenous immunoglobulin(HD-IVIG)impact therapy combined with prednisone on the basis of systematic chemotherapy to control the clonic symptoms of children with neuroblastoma(NB).Methods A retrospective analysis was made based on the clinical data of 8 NB children with combined clonus,who were admitted in Beijing Children's Hospital,Capital Medical University from May 2011 to February 2017.And analysis and summary were also made according to patients' clinical data,neurological symptoms,therapy methods and prognosis.The follow-up visiting was ended on March 1,2017.Results Eight patients were investigated,3 male and 5 female,with onset age ranged from 10.0 to 35.5 months (the median age was 17.5 months),and the period from occurrence of clonic symptoms to a definite diagnosis and starting treatment was 1.25 to 6.50 months (the median time was 3.60 months).All patients developed kinds of neurological syndrome clinically,such as clonus on the trunk and limbs,and 5 cases of them were involved in combined opsoclonus-myoclonus syndrome (OMS).All patients went for their first-time consultancy at the Neurology Department of Beijing Children's Hospital,Capital Medical University or local hospitals.The primary tumor focus was found in unilateral adrenal gland in 2 cases,1 case in bilateral adrenal glands,2 case in retroperitoneal region,2 cases in mediastinum and 1 cases in presacral region.The image examination indicated 1 case with a tumor focus,the diameter of it more than 5 cm.Except for 1 case involved in the local invasion of tumor in vertebral body,the images examination of all other patients showed the focus in the primary location,without visible distant metastasis or no abnormality was seen by head magnetic resonance imaging (MRI) examination.Initially,four cases had normal neuronal specific enolase (NSE) and 4 had higher NSE;one case had higher urine vanillylmandelic acid (VMA) and 7 normal;3 cases had higher urine homovanillic acid(HVA) and 5 normal.Among 8 patients,the pathological pattern of 6 cases was NB,in which 4 cases were of differentiated type and 2 cases of poorly differentiated type;the pathological pattern of 2 cases was ganglion cell NB,in which 1 case was of nodular type and 1 case of mixed type.N-MYC was not amplified.Clinical staging:5 cases of stage Ⅱ and 3 cases of stage Ⅲ.Clinical grouping:7 cases of intermediate risk group and 1 case of low risk group.So far,1 case lost follow-up in that the child didn't receive regular diagnosis and treatment due to economic problem,so significant improvement of clonic symptoms was not seen,all other patients were given the immunotherapy with intermittent HD-IVIG impact therapy and oral administration of prednisone based on systematic chemotherapy:immunoglobulin was applied respectively before,during and after chemotherapy in multiple impact treatments;3 cases received 4 courses of treatment,2 cases received 3 courses of treatment and 2 cases received 2 courses of treatment.Prednisone was given orally during the application of immunoglobulin,from the full dose and with the course of treatment of 1.0 to 5.5 months,3 months on average;then the dose was gradually reduced.With the follow-up up to now,hormone was discontinued in 4 cases and the total course of treatment was 8 to 12 months,10 months on average.One month after the treatment of patients in 4 cases,the clonic symptoms were improved or disappeared in 5 to 12 months;the clonus of patients in 2 cases was improved respectively 3 months after treatment and half a year after drug withdrawal,in which the symptoms of 1 case disappeared completely 1 year after treatment and the slight clonic symptoms of 1 case still existed by the update follow-up.Except for 1 case of patient lost to follow-up,the regular primary tumor focus of all patients indicated that the disease conditions were in a stable state.Conclusions The immunotherapy intermittently applied with HD-IVIG impact therapy in combination with prednisone based on regular systematic chemotherapy can effectively control the clonic symptoms of children with NB.The earlier the intervene treatment for clonic symptoms is recommended,so that the faster recovery of symptoms can be achieved.Early diagnosis and early treatment play a helpful role in the recovery of children with neurological symptoms.