伴副肿瘤综合征儿童神经母细胞瘤临床特征分析

目的探讨伴有副肿瘤综合征儿童神经母细胞瘤的临床特点、治疗策略及预后。方法回顾性分析湖南省儿童医院2010年1月至2019年12月收治的9例伴副肿瘤综合征神经母细胞瘤患者的临床资料,包括一般资料、副肿瘤综合征症状、肿瘤情况、治疗策略及预后。随访截至2020年6月1日。结果9例中男5例,女4例;起病年龄为19.0~48.2个月,出现副肿瘤综合征症状至确诊神经母细胞瘤后开始治疗时间为2.1~5.7个月;神经系统受累5例,消化系统受累2例,心血管系统受累1例,血液系统受累1例(骨髓未受累);组织学分类:神经母细胞瘤3例,其中预后良好型2例,预后不良型1例;节细胞性神经母细胞瘤6例,其中结节型2例,混杂型4例。国际神经母细胞瘤分期系统(International Neuroblastoma Staging System,INSS)临床分期:Ⅱ期7例,Ⅲ期2例。美国儿童肿瘤协作组(Children's Oncology Group,COG)危险度分组:低危组3例,中危组6例。肿瘤N-MYC基因均无扩增;采用手术、系统化疗和(或)间断大剂量人血丙种球蛋白、糖皮质激素治疗等综合治疗可缓解副肿瘤综合征;所有患者获有效随访,随访时间23.0~67.5个月,平均随访(34.5±8.2)个月,无事件生存率66.7%,总体生存率100%。结论副肿瘤综合征在儿童神经母细胞瘤中可累及多个系统,但以神经系统最为常见,尽早切除原发肿瘤病灶、系统化疗及免疫抑制等综合治疗可有效缓解副肿瘤综合征,伴副肿瘤综合征的儿童神经母细胞瘤预后良好。     

青少年和成人神经母细胞瘤诊疗策略和挑战：病例报告并文献复习

目的探讨青少年和成人神经母细胞瘤(neuroblastoma, NB)的临床特点、诊治经验及预后。方法本研究为回顾性研究, 以上海交通大学医学院附属新华医院接受治疗及随访的1例最初误诊为嗜铬细胞瘤(pheochromocytoma, PHEO)的24岁NB患者为研究对象, 对其诊断过程、接受抗双唾液酸神经节苷脂(disialoganglioside, GD2)单克隆抗体免疫治疗和间变性淋巴瘤激酶(anaplastic lymphoma kinase, ALK)抑制剂劳拉替尼靶向治疗的临床特点进行分析。以关键词"青少年和成人神经母细胞瘤"检索万方数据库及中国知网相关文献;以"adolescent and neuroblastoma"或"adult and neuroblastoma"为检索词, 检索PubMed数据库相关文献。检索截止日期为2021年12月。排除14岁以下和原发颅内NB病例后进行文献复习, 总结该群体NB的临床特征、治疗方法以及治疗结局情况。结果患者男, 24岁, 因体检发现腹部肿块入院, 肿瘤原发部位为右侧肾上腺, 有淋巴结和骨转移, 手术切除腹部肿瘤, 经多次病理复核...     

新生儿期神经母细胞瘤三例

神经母细胞瘤(Neuroblastoma N B)是胚胎性交感神经系统肿瘤,为儿童常见实体瘤之一。占胚胎性肿瘤发病率8.7人/百万,5岁前发病率1/7000,近1/4发生在一岁以下,最幼者仅数月、数天,甚至分娩时肿瘤已存在,称先天性神经母细胞瘤。在新生儿期其临床特征,病期转归及预后,均有异于其他年龄组,目前尚少报告,今将临床所遇经病理证实3例,结合文献复习,特报告如下。临床资料3例男婴神经母细胞瘤的临床、病理资料见附表。     

氯雷他定治疗儿童哮喘的疗效与安全性评价

目的：评价新一代抗组胺药物氯雷他定治疗儿童哮喘的疗效和安全性,为儿童哮喘的治疗提供临床依据。方法：采用计算机及手工检索方式检索PubMed、MEDLINE、EMBASE、Cochrance、CNKI、CBMdisc等数据库（1990年1月至2010年12月）。对文献质量进行内部真实性评价,并按Cochrane协作网推荐的方法进行系统评价和分析。结果：检索到文献179篇,最终纳入11篇随机对照研究,共有317例哮喘儿童,其中氯雷他定治疗组159例,安慰剂治疗组（对照组）158例。所有纳入文献质量为B级。Meta分析的结果表明,治疗后氯雷他定组的临床评分、4周和8周的一秒用力呼气容积（FEV1）、8周的呼吸流速峰值（PEFR）均明显优于对照组（P<0.01）,差异均有统计学意义。而氯雷他定组乏力和心动过速及心悸的发生比率均低于对照组,差异有统计学意义。结论：采用氯雷他定治疗儿童哮喘安全有效,值得在临床进行推广。     

神经母细胞瘤造血干细胞移植治疗的进展

神经母细胞瘤是婴幼儿最常见的颅外神经系统来源的实体肿瘤, 异质性较强, 不同分期的预后差异极大, 高危组预后不良。神经母细胞瘤的治疗方案包括手术、化疗、放疗及造血干细胞移植等, 各具优缺点。目前高剂量化疗联合自体干细胞移植是儿童高危神经母细胞瘤的一线治疗方法。现综述近年有关神经母细胞瘤造血干细胞移植治疗的新进展。     

孟鲁司特治疗婴幼儿喘息疗效和安全性系统评价

目的 评价孟鲁司特对<2岁喘息患儿的疗效及安全性。方法 计算机检索EMBASE、PubMed、在研对照试验数据库、Cochrane图书馆、中文科技期刊全文数据库、中国期刊全文数据库和万方数字化期刊群,检索时间均从建库至2010年3月。并手工检索相关会议论文集、药厂资料及所有纳入文献的参考文献,获得孟鲁司特治疗<2岁喘息患儿安慰剂对照的RCT文献。采用Cochrane评价手册5.0.2推荐的方法评估纳入文献的方法学质量。以喘息相关病死率、临床症状评分和β2受体激动剂、糖皮质激素需求量为主要结局指标,以不良反应发生率和生活质量为次要结局指标。对无法进行定量合并的文献进行描述性分析。结果 共检索到相关文献906篇,其中符合纳入标准的6篇RCT文献进入系统评价。5篇文献为在研对照数据库登记的研究。纳入对象为喘息患儿。文献质量评价结果显示：4篇文献详细描述了随机化分组的方法,3篇文献描述了分配隐藏,6篇文献均采用双盲法,5篇文献存在选择性报告研究结果,2篇文献描述了其他偏倚来源。2篇RCT文献的失访率较高（分别为21.7%和32.1%）。因各纳入文献间存在明显的临床异质性,无法进行Meta分析,故而描述性分析。①纳入文献均无喘息相关死亡的报道;②孟鲁司特4 mg·d-1或8 mg·d-1组临床症状评分、使用β2受体激动剂和糖皮质激素等,与安慰剂组差异均无统计学意义（均P>0.05）;③纳入文献均报道了研究过程中药物不良反应的发生率,患儿对孟鲁司特有较好的耐受性。孟鲁司特组和安慰剂组不良反应发生率差异无统计学意义（P>0.05）。6篇文献均没有生活质量的评价指标。结论 现有研究尚不能证实孟鲁司特治疗<2岁婴幼儿喘息有效,治疗20周也未见明显的不良反应。     

新生儿期神经母细胞瘤3例报告

神经母细胞瘤(NB)是胚胎性交感神经系统肿瘤,为儿童常见实体瘤之一,5岁前发病率为1/7000,近1/4发生在1岁以下,最幼者仅数月、数天,甚至分娩时肿瘤已存在,称先天性神经母细胞瘤.此期临床特点及预后,均有异于年长儿,今将临床所遇经病理证实的新生儿期神经母细胞瘤3例报告如下.临床资料见附表.     

应用血肌酸激酶或肌酸激酶MM同工酶筛查新生儿杜氏肌营养不良症的系统评价/Meta分析

背景：目前应用血CK或其同工酶（CK MM）筛查新生儿杜氏肌营养不良症（DMD）的临床研究较少,其准确性尚不明确。 目的：系统评价血CK或CK MM筛查新生儿DMD的准确性。 设计：系统评价/Meta分析。 方法：检索Medline（PubMed）、Embase、Cochrane Library、Web of Science、Scopus、中国知网数据库、中国生物医学文献数据库、万方数据库和维普中文期刊全文数据库,检索起始时间均为1975年1月1日,Medline（PubMed）检索截止时间为2022年11 月5日,其他数据库检索截止时间为2022年10月5日。纳入以血CK或CK MM筛查新生儿DMD的诊断准确性研究。采用QUADAS 2量表对纳入文献进行偏倚风险及临床适用性评价;提取文献数据,应用Stata 15.0和Meta Disc 1.4软件进行Meta分析;合并敏感度、特异度、阳性似然比（PLR）、阴性似然比(NLR)、诊断比值比(DOR),并绘制综合受试者工作特征曲线（SROC）,计算AUC和Q指数值。 主要结局指标：敏感度和特异度。 结果：CK筛查DMD纳入11篇文献,共1 351 953例新生儿;敏感度97%（95%CI:88%～99%）,特异度100%（95%CI:100%～100%）,PLR 1 131（95%CI:370～3 455）,NLR 0.01（95%CI:0.00～0.19）,DOR 16 476 (95%CI:4 115~65 963),AUC为0.995 4,Q指数为0.974 0;Deeks检验P=0.12,发表偏倚的可能较小。CK MM筛查DMD纳入5篇文献,共156 547例新生儿;敏感度和特异度均为100%（95%CI:100%~100%）,PLR 3 925（95%CI: 3 925~3 925）,NLR 0.00（95%CI:0.00~0.00）,DOR 23 094 (95%CI:5 773~92 384);AUC为0.925 2,Q指数为0.859 4。 结论:应用血CK或CK MM筛查新生儿DMD的准确性高,有助于早期诊断DMD。     

上海地区10万儿童神经母细胞瘤的群体筛查

上海地区１０万儿童神经母细胞瘤的群体筛查汤静燕王耀平朱亚忠方建华小儿神经母细胞瘤（ＮＢ）是儿童常见的实体瘤之一，由于它早期分泌儿茶酚胺代谢产物并从尿中排出，因此可以通过筛查尿中的儿茶酚胺代谢产物来发现早期肿瘤，以改变患儿的预后。为此，自１９９２年５月...     

糖皮质激素预防过敏性紫癜患儿肾损害随机对照试验的Meta分析

目的 评价糖皮质激素对过敏性紫癜（HSP）患儿肾损害的预防作用。方法 检索Cochrane图书馆、Medline、EMBASE、中国期刊全文数据库、万方数据库、中文科技期刊全文数据库等,收集有关糖皮质激素预防HSP患儿肾损害的RCT或类随机对照试验（quasi-RCT）文献,检索文献起止时间均为1990年1月至2012年6月。由2名作者进行资料提取和文献质量评价。应用RevMan 4.3软件进行Meta分析,根据异质性结果选择相应的效应模型分析;无法进行Meta分析时采用描述性分析。结果 5篇RCT和1篇quasi-RCT进入Meta分析。4篇文献描述了具体随机化方法,采用了充分的分配隐藏和盲法,纳入6篇文献均报道了失访和退出情况;4篇为低度偏倚风险,2篇为高度偏倚风险。Meta分析结果显示,诊断HSP后6个月以内肾损害的发生率,糖皮质激素预防组为22.2%(42/189),对照组为26.3%(50/190),合并RR=0.67（95%CI: 0.17～2.62）,差异无统计学意义,P=0.57;诊断HSP后6个月以上肾损害发生率,糖皮质激素预防组为109%(41/373),对照组为12.6%(46/364),合并RR=0.85（95%CI: 0.44～1.64）,差异无统计学意义,P=0.65。剔除2篇高度偏倚风险文献行敏感性分析,结果无改变。结论 本Meta分析结果尚不支持早期糖皮质激素治疗能预防HSP患儿肾脏损害。建议临床医生根据患儿具体临床表现和实验室检查,慎重应用糖皮质激素或辅以抗凝、抗过敏等对症治疗。     

Locoregional MYCN-amplified neuroblastoma

MYCN-amplification is strongly associated with other high-risk prognostic factors and poor outcome in neuroblastoma. Infrequently, amplification of MYCN has been identified in localized tumors with favorable biologic features. Outcome for these children is difficult to predict and optimal treatment strategies remain unclear. We report a 5-month-old who presented with an MYCN-amplified INSS stage 3, pelvic neuroblastoma. The tumor had favorable histology, hyperdiploidy, and lacked 1p36 and 11q23 aberrations. Although the patient met the criteria for high-risk neuroblastoma, because of the discordant prognostic markers we elected to treat her according to an intermediate-risk protocol. She remains event-free more than 18 months.     

Neuroblastoma in children: Update on clinicopathologic and genetic prognostic factors

Neuroblastoma is the most common extracranial solid tumor in childhood accounting for 8–10% of all childhood malignancies. The tumor is characterized by a spectrum of histopathologic features and a heterogeneous clinical phenotype. Modern multimodality therapy results in variable clinical response ranging from cure in localized tumors to limited response in aggressive metastatic disease. Accurate clinical staging and risk assessment based on clinical, surgical, biologic and pathologic criteria are of pivotal importance in assigning prognosis and planning effective treatment approaches. Numerous studies have analyzed the presence of several clinicopathologic and biologic factors in association with the patient's prognosis and outcome. Although patient's age, tumor stage, histopathologic classification, and MYCN amplification are the most commonly validated prognostic markers, several new gene mutations have been identified in sporadic and familial neuroblastoma cases that show association with an adverse outcome. Novel molecular studies have also added data on chromosomal segmental aberrations in MYCN nonamplified tumors. In this review, we provide an updated summary of the clinical, serologic and genetic prognostic indicators in neuroblastoma including classic factors that have consistently played a role in risk stratification of patients as well as newly discovered biomarkers that may show a potential significance in patients' management.     

The role of genetic and epigenetic alterations in neuroblastoma disease pathogenesis

Neuroblastoma is a highly heterogeneous tumor accounting for 15 % of all pediatric cancer deaths. Clinical behavior ranges from the spontaneous regression of localized, asymptomatic tumors, as well as metastasized tumors in infants, to rapid progression and resistance to therapy. Genomic amplification of the MYCN oncogene has been used to predict outcome in neuroblastoma for over 30 years, however, recent methodological advances including miRNA and mRNA profiling, comparative genomic hybridization (array-CGH), and whole-genome sequencing have enabled the detailed analysis of the neuroblastoma genome, leading to the identification of new prognostic markers and better patient stratification. In this review, we will describe the main genetic factors responsible for these diverse clinical phenotypes in neuroblastoma, the chronology of their discovery, and the impact on patient prognosis.     

The biologic basis for neuroblastoma heterogeneity and risk stratification

PURPOSE OF REVIEW: Neuroblastoma serves as the paradigm for the clinical utility of tumor-specific biologic data for prognostication. This review will describe the genetic and biologic basis for the diverse clinical phenotypes observed in neuroblastoma patients. It will also discuss the current approach to risk classification and how this may change in the future. RECENT FINDINGS: The biologic basis of neuroblastoma has come into clearer focus. PHOX2B is the first bona fide neuroblastoma predisposition gene identified, but is mutated in only a small subset of cases. Somatically acquired alterations at chromosome arms 3p and 11q are highly correlated with acquisition of metastases in the absence of MYCN amplification and may be useful as prognostic markers. The Children's Oncology Group risk classification system has been validated, with current emphasis on further refinement such as reevaluation of the age cutoff used to stratify therapy, and incorporation of additional molecular genetic markers is being studied prospectively. High-throughput genome scale analyses of neuroblastomas are further clarifying the genetic basis of this heterogeneous disease. SUMMARY: Neuroblastoma remains a significant challenge as high-risk patients are treated with intensive multimodal therapies but cure rates remain suboptimal. There is remarkable heterogeneity observed in tumor phenotype, ranging from spontaneous regression to relentless progression. There are literally dozens of clinical and biologic markers that have been proposed as being predictive of disease outcome, but large clinical correlative studies are sharpening the focus of which markers can be used by the clinician to optimize therapy for an individual patient.     

Congenital malformation syndromes associated with peripheral neuroblastic tumors: A systematic review

Malformation syndromes with predisposition to peripheral neuroblastic tumors (pNT), including neuroblastoma, ganglioneuroblastoma, and ganglioneuroma, may provide clues to critical mutations influencing pNT development. Our objective was to identify and characterize features of pNT associated with specific malformation syndromes. A systematic review of the literature was performed using MEDLINE, Scopus, and Web of Science. We identified 154 of 1014 papers that met eligibility, comprising 207 cases. The patient's age, tumor histology, and frequency of multiple primary tumors varied by malformation syndrome. Genomic studies and systematized reporting are necessary to elucidate cancer risk and the distinct clinical and biological pNT patterns within syndromes.     

Surgical management of neuroblastoma

Neuroblastoma treatment remains challenging but has been advanced by the establishment of clinical and biological variables that determine prognostic risk. Risk-based therapy currently is the hallmark of neuroblastoma treatment. Initially, stage and age were the prime determinants of survival used in clinical practice. The Shimada histopathologic classification added to the former 2 and biochemical markers like the serum ferritin, lactic dehydrogenase, and neuron-specific enolase also provided information regarding prognosis. The current era of neuroblastoma therapy has been influenced heavily by advances in molecular biology, most notably the identification of the MYCN oncogene and the application of recombinant DNA methods to identification of chromosomal deletions. Current risk assessment includes age, stage, histopathology, and biochemical markers but also analyses performed on DNA extracted from fresh tumors. This places the onus of obtaining an adequate quantity and quality of fresh neuroblastoma tissue directly on the pediatric surgeon who performs the initial biopsy.     

Telomerase is a strong indicator for assessing the proneness to progression in neuroblastomas

BACKGROUND: As traditional parameters do not ensure completely accurate prognostic grouping in neuroblastoma (NB), new molecular markers are needed for assessing the individual patient's prognosis more precisely. PROCEDURE, RESULTS, AND CONCLUSIONS: Based on 133 NB, we show that telomerase activity (TA) is a powerful, independent prognostic marker for all stages and is capable of differentiating between good and poor outcome in putative 'favorable' clinical or biological subgroups of NB patients. Analysis of gene and protein expression of telomerase subunits suggests that the presence or absence of TA in NB is strongly correlated with expression levels of both the catalytic subunit hTERT and the internal RNA component (hTR).     

Neonatal oncology.

All known tumor types have been reported in the neonate. A numerical listing and discussion are beyond the scope of this review. Wells and Fraumeni give some insight into common congenital malignant neoplasms. Table 2 lists the percentage of neonatal deaths caused by type-specific cancers. Retinoblastoma is probably the most common malignant tumor in the neonate. About seven per cent of these tumors have been apparent at birth. This tumor is not discussed in either article because it is not lethal until muypes in neonatal and pediatric patients. Some congenital malformations in the in the neonate are recognized as being frankly benign (cysts), potentially malignant (teratomas), and frankly malignant (neuroblastoma). A high percentage of teratomas are benign in the newborn period. Leukemia in the newborn appears to be more aggressive yet neuroblastoma has a better prognosis. More studies are needed to help us define why the neonate does better with some tumors and worse with others. Surface cell markers on neonatal leukemia, B and T cell function studies, and other immunologic surveillance studies are needed. Study of neonatal oncology may add to our knowledge of carcinogenesis and oncogenesis in the future.