Case selection in minimally invasive surgical treatment of neuroblastoma

PURPOSE: The experience with minimally invasive surgery (MIS) in the treatment of neuroblastoma (NB) is anecdotal. The purpose of this study was to evaluate a retrospective cohort of NB patients who underwent MIS resection of their primary tumors. METHODS: A retrospective study of NB patients who underwent MIS resection of their primary tumors over a 3-year period was undertaken. Study outcomes included complications, completeness of resection, and event-free and overall short-term survival. RESULTS: Of a total of 21 children who underwent surgical resection for NB during the period of study, 8 (38%) underwent selected MIS resection. Six of the eight (75%) tumors were adrenal in origin and the remainder were located in the posterior mediastinum. Distribution by International Neuroblastoma Staging System (INSS) stage was: stage 1 (3), stage 2 (2), and stage 4 (3). One stage 4 tumor was N-myc amplified. All stage 4 patients experienced a >50% tumor volume cytoreduction in response to preoperative chemotherapy. All MIS resections were performed without need for blood transfusion, or conversion to open procedure, and there were no perioperative complications. All eight patients were alive and disease-free at a median 18-month follow-up. CONCLUSIONS: With appropriate preoperative case selection based on anatomic features, MIS tumor resection in patients with NB can be performed safely and effectively.     

SNHG7-miR-653-5p-STAT2反馈通路在神经母细胞瘤进展中的调节作用研究

目的 研究lncRNA SNHG7在神经母细胞瘤(neuroblastoma,NB)进展中的作用,以及SNHG7-miR-653-5p-STAT2反馈通路在神经母细胞瘤进展中的调节作用.方法 从青岛大学附属医院收治的NB患儿体内获得92对NB组织及相邻非肿瘤组织.采用qRT-PCR检测SNHG7在神经母细胞瘤肿瘤组织及...     

SNHG7-miR-653-5p-STAT2反馈通路在神经母细胞瘤进展中的调节作用研究CSCD

目的研究lncRNA SNHG7在神经母细胞瘤(neuroblastoma,NB)进展中的作用,以及SNHG7-miR-653-5p-STAT2反馈通路在神经母细胞瘤进展中的调节作用。方法从青岛大学附属医院收治的NB患儿体内获得92对NB组织及相邻非肿瘤组织。采用qRT-PCR检测SNHG7在神经母细胞瘤肿瘤组织及细胞中的表达情况。采用Kaplan-Meier分析神经母细胞瘤患儿的总体存活率。采用比色法(MTT法)和集落形成法检测SNHG7对SK-N-SH和SH-SY5Y细胞的作用。采用Transwell侵袭及迁移试验检测SK-N-SH和SH-SY5Y细胞的侵袭和迁移能力。采用荧光素酶检测miR-653-5p和SNHG7、STAT2之间的作用。采用RIP测定及RNA下拉测定检验SNHG7和miR-653-5p在NB中的相对表达情况。采用Spearman相关分析探究SNHG7与miR-653-5p、STAT2的相关性。结果qRT-PCR显示,92对NB组织及相邻非肿瘤组织中,肿瘤组织(n=53)中SNHG7的表达量高于非肿瘤组织(n=39)。SNHG7高表达的NB患儿(n=53)总生存期随月份的增加而逐渐降低,SNHG7低表达的NB患儿(n=39)总生存期随月份的增加也逐渐降低,两组差异有统计学意义(P=0.004)。细胞功能试验:①MTT法和集落形成法检测结果显示,SNHG7的下调对SK-N-SH和SH-SY5Y细胞的存活和增殖有明显抑制作用;②Transwell试验检测结果显示,敲低SNHG7可明显抑制SK-N-SH和SH-SY5Y细胞的细胞迁移和侵袭能力(P<0.05);③荧光素酶检测显示,miR-653-5p能降低SNHG7-WT(野生型)的荧光素酶活性,且miR-653-5p与STAT2-WT(野生型)之间存在特异性的相互作用。Spearman相关分析显示:①NB组织中SNHG7与miR-653-5p表达水平呈负相关(r=-0.281,P=0.007);②STAT2的表达量与NB组织中miR-653-5p表达水平呈负相关(r=-0.295,P=0.004),STAT2的表达量与NB组织中SNHG7表达水平呈正相关(r=0.296,P=0.004)。结论SNHG7通过miR-653-5p/STAT2通路促使NB进展,这为NB提供了一个新的治疗靶点和预测预后的生物标志物。     

5岁以上神经母细胞瘤患者的临床特点及疗效分析

目的 总结5岁以上神经母细胞瘤（NB）患儿的临床特点及疗效,为改善其预后提供理论基础。方法 回顾性分析54例初治NB患儿临床资料,进行临床特点、疗效总结以及Kaplan-Meier生存分析。结果 54例患儿中男36例、女18例,均为3、4期。以腹膜后占位最多见（76%,41/54）,其次为纵隔占位（18%,10/54）、椎管内占位（4%,2/54）和盆腔占位（2%,1/54）。截止至随访日期,54例患儿中存活30例（56%）：无病生存23例（77%,其中9例为复发再度化疗后完全缓解）、肿瘤部分缓解6例（20%,均为复发再度化疗患儿）、进展1例（3%,为复发再度化疗后进展）;死亡24例（44%）,其中22例为复发再度化疗后死亡、2例为初治期间多脏器衰竭死亡;治疗、随访期间共38例复发。Kaplan-Meier生存分析提示：54例患儿平均生存时间53.8个月;3期患儿总生存率（OS）为80%,高于4期患儿（53%）,差异具有统计学意义（P < 0.01）;复发患儿平均生存时间（51.68个月）低于无复发病例（62.57个月）,差异有统计学意义（P < 0.01）。结论 年长儿NB临床分期多属晚期,但规律治疗仍可提高疗效,应增加患儿信心,坚持规范治疗。     

神经生长因子受体对神经母细胞瘤血管生成作用的研究(英文)

目的　神经生长因子受体 (TrkA)基因是神经母细胞瘤 (NB)良好预后的标识之一 ,其高表达不仅可以抑制NB增殖和诱导良性分化 ,对NB的血管生长可能有一定的影响。该实验探讨TrkA基因对NB血管生成的作用。方法　 1 5只裸鼠随机分为对照组、空载体组和实验组 (每组 5只 )。利用脂质体转染法将TrkA基因和pBPSTR1空载体转入NBSY5Y细胞 ,分别命名为SY5Y TrkA及SY5Y Vec细胞 ,未转染细胞为SY5Y细胞。将SY5Y ,SY5Y Vec ,SY5Y TrkA细胞分别接种在对照组、空载体组和实验组裸鼠皮下 ,接种 5 0d后处死动物 ,切除肿瘤 ,测量肿瘤体积 ;用RT PCR及免疫组织化学技术检测肿瘤内血管内皮生长因子 (VEGF)的表达 ;计算微血管密度 (MVD)。结果　SY5Y TrkA细胞TrkA表达明显高于SY5Y Vec及SY5Y细胞组 (P <0 .0 1 ) ;实验组肿瘤终体积小于对照组及空载体组 (0 .39± 0 .0 2cm3 vs 1 .74± 0 .4 9cm3 ) ;(0 .39± 0 .0 2cm3 vs 1 .80± 0 .75cm3 ) ,差异有显著性 (均P <0 .0 1 ) ;实验组VEGFmRNA表达低于对照组及空载体组 (0 .1 6± 0 .0 9vs 1 .4 5± 0 .77) ;(0 .1 6± 0 .0 9vs 1 .35± 0 .71 ) ,差异有显著性 (均P <0 .0 1 ) ;实验组VEGF蛋白表达低于对照组及空载体组 (2 .0 0± 0 .6 0vs 5 .6 7± 0 .4 9) ;(2 .0 0± 0 .6 0v     

Radical excision of primary tumor and lymph nodes in advanced neuroblastoma: combination with intensive induction chemotherapy

The role of surgery in the management of children with advanced neuroblastoma is still unclear; no radical surgical technique for resection of primary tumor and lymph nodes has been established. A radical procedure was developed and has been employed in 13 patients over 1 year of age with stage III or IV disease since 1985, together with intensive induction chemotherapy. For abdominal neuroblastoma, the area of retroperitoneal lymph node dissection was divided into six sections: to the left of the abdominal aorta, between the aorta and vena cava, and to the right of the vena cava, with further subdivision according to the level of the renal vein. After excision of the primary tumor, lymph node dissection was carried out systematically in all six sections; gross complete resection was possible in 12 of the 13 patients. All 12 patients attained complete remission at least once in the course of treatment, and 7 underwent autologous bone marrow transplantation. It is noteworthy that local control of the disease was satisfactory in all but 1 patient who had extensive involvement of both renal hila and showed recurrence in the remaining kidney. Eight patients are alive with an average follow-up of 44 months; 7 of them show no signs of disease. After reviewing the results of our previous series and this series, it was concluded that advances in operative techniques and the introduction of intensive induction chemotherapy did increase surgical resectability, the rate of complete remission, and the number of candidates for bone marrow transplantation. Improvement of survival in patients with advanced neuroblastoma may thus be expected. Offprint requests to: Y. Tsuchida     

Caspase-8在TRAIL诱导神经母细胞瘤细胞凋亡中的作用

目的：应用干扰素(IFNγ)诱导神经母细胞瘤（neuroblastoma, NB）细胞caspase 8的表达并观察其是否可以恢复NB细胞对肿瘤坏死因子相关凋亡诱导配体（TRAIL）的敏感性。方法：应用RT PCR方法检测IFNγ作用前后NB细胞caspase-8 mRNA的表达;应用Alamar Blue法及流式细胞术检测IFNγ、TRAIL、IFNγ+TRAIL、IFNγ+caspase-8抑制剂zIETD-FMK+TRAIL对NB细胞生长及凋亡的影响;应用比色法测定NB细胞caspase-8相对活性。结果：对TRAIL敏感的CHP212细胞表达caspase-8,且经IFNγ处理后caspase-8 表达水平逐步增加;对TRAIL不敏感的SY5Y细胞不表达caspase-8,IFNγ作用后其caspase-8 mRNA表达明显增加。IFNγ与TRAIL联用对SY5Y细胞有明显诱导凋亡作用。CHP212细胞caspase-8相对活性随TRAIL作用时间的延长逐步升高;IFNγ与TRAIL联合作用的SY5Y细胞caspase-8相对活性明显高于未加药物处理的对照组、IFNγ组、TRAIL组及抑制剂组。结论：表达caspase-8的NB细胞对TRAIL的诱导凋亡作用敏感,TRAIL诱导NB细胞凋亡过程中伴随caspase-8活性的增加。［中国当代儿科杂志,2010,12(11)：902-907］     

先天性神经母细胞瘤发病机制与临床特点的研究进展

神经母细胞瘤是儿童最常见的颅外实体肿瘤,来源于肾上腺髓质或交感神经节.先天性神经母细胞瘤约占神经母细胞瘤患儿总数的5％,大多数患儿于出生后1个月内确诊.与1岁以上神经母细胞瘤患儿相比,新生儿神经母细胞瘤有其独特的病程.本文就先天性神经母细胞瘤的发病机制、临床表现、治疗方法以及预测患儿长期预后的生物学因素进行综述.     

关于神经母细胞瘤外科治疗的几点思考

神经母细胞瘤手术复杂危险,极具挑战.尽管外科手术的水平高低难以被科学定量评估,且这种艰苦手术对于患儿生存获益的贡献还有不同的意见,但就神经母细胞瘤治疗而言,外科手术仍然是必须的,而且要努力做到更好.临床应努力创新各种技术方法,拓展微创手术,提高神经母细胞瘤的外科治疗效果.     

microRNA在神经母细胞瘤的研究进展

神经母细胞瘤是儿童最常见的颅外恶性实体肿瘤,肿瘤转移及复发是其死亡的重要原因.神经母细胞瘤的发生与胚胎发育异常密切相关,但其确切的发病机制、分化成熟及转移的机制并未完全阐明.微小RNA在机体胚胎发育过程和肿瘤的发生中起到重要作用,并与肿瘤发展及预后密切相关.该文就微小RNA在神经母细胞瘤的研究进展作一综述.     

神经母细胞瘤中hTR、hTERT基因的表达

目的探讨人端粒酶RNA（hTR）、人端粒酶逆转录酶（hTERT）基因在神经母细胞瘤自然逆转成熟及恶性增殖中的表达及其意义。方法应用原位杂交方法检测34例神经母细胞瘤、5例神经节神经母细胞瘤、8例神经节细胞瘤、16例胎儿肾上腺髓质、20例新生儿肾上腺髓质中hTR、hTERT基因的表达。结果hTR、hTERT基因在病理分型F型中的阳性表达均为46．15％（6／13）；uF型中阳性表达分别是85．71％（18／21）、90．48％（19／21）；两组比较差异有显著性意义（X^2=6．05，P〈0．05；X^2=8．10，P〈0．05）。在神经节神经母细胞瘤中hTR、hTERT基因的阳性表达均为20％。神经节细胞瘤中hTR、hTERT基因的阳性表达分别是25％、12．5％；二组与神经母细胞瘤比较差异有显著性意义（X^2=11．70，P〈0．05；X^2=10．81，P〈0．05）。在胎儿及新生儿肾上腺髓质中hTR、hTERT基因为弱阳性及阴性。结论在神经母细胞自然逆转成熟及恶性增殖是时hTR、hTERT起了重要的作用，当hTR、hTERT基因表达减弱，神经母细胞具有自然逆转成熟的趋势，当hTR、hTERT基因表达阳性，提示神经母细胞增殖力增强，因此hTR、hTERT基因的表达可作临床判断预后的指标。     

Intensive chemotherapy in children with stage IV neuroblastoma

A retrospective analysis of effectiveness of sequential chemotherapy with cyclophosphamide, doxorubicin, cisplatin and etoposide in children with stage IV neuroblastoma was undertaken. Study group included 17 children of mores than one year old with median age of 3 years (range 18 months to 7 years). Fourteen were males and three females. Sites of primary tumor were abdomen in 12 patients, pelvis in 3, paravertebral in 1 and unknown in 1. Metastatic sites included bone marrow (88%), bone (82%), orbit (29.4%) and lymph node (11.7%). One patient had brain parenchymal disease and another had cerebrospinal fluid positivity for malignant cells. Fifteen of the 17 patients had major response with chemotherapy (complete response in two and partial response in 13). Ten of the 15 patients completed four courses of chemotherapy and five patients progressed while on chemotherapy and died. Only two of the ten patients, who had four courses chemotherapy are alive after 2 years. Hence the 2-year survival in this series is 11.7%. There was no toxic death in this study.     

Management of Wilms' tumor and neuroblastoma

Wilms' tumor and neuroblastoma resemble each other in usual presentation and by their occurrence in young children. However they represent a dichotomy in advances in treatment. In Wilms' tumor, survival of patients has dramatically improved as a result, of multimodal therapy, whereas in neuroblastoma little advance in treatment has occurred. Development of rational chemotherapeutic regimens through better understanding of drugs and of cell cycle kinetics as well as investigation of other modalities of therapy, i.e. immunotherapy, etc., may be helpful in improving survival in the years to come.     

Effects of the mass screenings for neuroblastoma in Japan

Sixty-eight cases of neuroblastoma detected during mass screening being performed by 11 local self-governing bodies of Japan were studied concerning age, clinical stage, and survival rate. Their average ages at the first screening, at the beginning of thorough examination, and at the start of therapy were 215.7, 245.6, and 264.7 days, respectively. This screening, which is aimed at the 6-month-old infants is considered to be acceptable, on the grounds that the majority of the cases (95.6%) were asymptomatic at the time of thorough examination, that for most of the cases (98.5%) the initiation of therapy was at under 1 year of age, and that their 60-month survival rate was 87.5%. However, there seems to be room for discussion of the best age at which subjects should be screened, because the 68 cases included some patients already with advanced stages at the time of thorough examination, and because false negative cases were identified besides the 68 positive cases.Abbreviations VMA vanillylmandelic acid - HVA homovanillic acid     

IFNγ联合TRAIL诱导神经母细胞瘤细胞凋亡的研究

目的探讨IENγ（γ干扰素）对TRAIL（肿瘤坏死因子相关凋亡诱导配体）诱导神经母细胞瘤细胞株SMS-KCNR（KCNR）细胞凋亡的影响及其发生机制。方法应用RT-PCR方法检测IFNγ作用前后KCNR细胞Caspase8的表达；应用四甲基偶氮唑蓝（MTT）比色法及流式细胞仪（FCM）检测IFNγ、TRAIL、IFNγ＋TRAIL及IFNγ＋Caspase8抑制剂（zIETD-FMK）＋TRAIL对KCNR细胞生长及凋亡的影响；应用比色法测定Caspase8相对活性。结果KCNR细胞不表达Caspase8，IFNγ作用48h后的KCNR细胞Caspase8表达明显增加；KCNR细胞对TRAIL不敏感，IFNγ诱导表达Caspase8的KCNR细胞对TRAIL敏感；IFNγ＋TRAIL组Caspase8相对活性明显高于TRAIL组及抑制剂组；zIETD-FMK能阻断Caspase8的活化而抑制TRAIL对KCNR细胞的诱导凋亡作用。结论IFNγ通过诱导Caspase8表达而逆转KCNR细胞对TRAIL诱导凋亡的耐受。     

Wilms' tumor and neuroblastoma

Significant differences exist between the European and North American treatment protocols for Wilms' tumor and neuroblastoma. There are variations in biopsy technique, timing and extent of initial surgery, chemotherapy protocols and dosage routines, as well as the type of salvage therapy. With the consolidation of the two major North American study groups into a single entity (Children's Oncology Group), the European and North American study groups represent the only remaining large-scale venues for treatment comparison. It is important to study and understand the variation in treatment protocols in order to maintain an open forum of scientific investigation that will lead to improving the care and outcome of children with cancer. It is anticipated that the unification of the North American groups will lead to greater interest and scientific cooperation with the European study group. This paper will serve as a forum for such a discussion at a local level.     

神经母细胞瘤多药耐药机制的研究

神经母细胞瘤(neuroblastoma,NB)是儿童最常见的颅外实体恶性肿瘤,临床表现多种多样,肿瘤转移及复发是其死亡的主要原因.目前NB治疗方法主要集中在手术治疗、系统化疗、放射治疗、清髓治疗联合移植、肿瘤靶向治疗等,但高危患儿的治疗效果仍不容乐观.研究表明多药耐药(multidrug resist-ance,MDR)是成功治疗NB的主要障碍,因此全面认识NB耐药机制对于提高患儿生存率具有十分重要的意义.该文从多方面就NB耐药机制进行综述.     

Cochrane系统评价方法对神经母细胞瘤分子与生物标记物的Meta分析

目的针对神经母细胞瘤已报道的生物标记进行系统评价及Meta分析,评价他们在筛查、诊断、预后以及检测治疗中的临床价值。方法对1990￣2007年的相关文献应用定义明确的检索策略进行文献检索。运用Cochrane系统评价方法,检索Cochrane图书馆临床对照试验资料库(2007年第2期)、PubMed(1990～2007年)、Embase(1990～2007年)和Cancerlit,应用RevMan4.2软件进行统计分析。结果共有536篇研究论文,报道208种不同的肿瘤标记,涉及筛查、诊断、检测及预后等4种临床相关的研究领域。样本量小,统计报告质量差,异质性大以及出版偏倚等是研究报告中存在的主要问题,限制了数据抽出合并等定量分析处理过程。预后研究文献量相对较大,进行Meta分析显示,MYCN、染色体1p、CD44及多药耐药等13种标记是潜在的重要预后判断工具。结论系统评价是神经母细胞瘤肿瘤标记的重要研究方法,可进一步确定一些重要的肿瘤标记,在将来的研究及治疗策略中需引起重视。另外,通过系统评价可以突出显示原始肿瘤标记研究中存在的普遍问题,例如报告的异质性及质量较差。这些问题需要更适当的临床研究提供证据。肿瘤研究...     

小儿神经母细胞瘤17例报告

目的总结小儿神经母细胞瘤(NB)的诊断与治疗经验。方法根据病理、骨髓、影像学、尿3-甲氨基-4羟基杏仁酸(VMA)测定,分析17例NB临床资料。结果男10例,女7例。平均年龄5·3岁。就诊前平均病程2·8月。后腹膜为首发部位占11/17(64·7%)。主要症状为发热9/17(53%)。主要体征为肿块占17/17(100%)。诊断:病理确诊者16例;影像加胸水培养发现神经细胞1例。病理分类:病理确诊的16例中,神经母细胞瘤者12例,神经节母细胞瘤者4例。临床分期:Ⅳ期13例;Ⅲ期2例;Ⅱ期2例。其它化验:乳酸脱氢酶(LDH)共做7例均增高。ESR共做3例均增高。Hb共做17例,降低4例,平均102·6g/L,范围64~122g/L。治疗:Ⅲ、Ⅳ期者在化疗前或化疗中择期手术,Ⅱ期者手术后化疗。15例未坚持完成治疗,未治自动出院1例,正在治疗1例。结论①对骨关节肌肉疼痛、发热、体检未发现任何阳性体征,但影像学发现腹腔结节或肿物,排除感染性疾病以后,医生应提高警惕,早作腹腔探查术。②对术前已确诊的病例,需由多学科(小儿肿瘤内科、病理科、手术科、放疗科、放射科)密切配合,联合讨论最佳的治疗方案。③外科医生术中要提供分期的重要依据,以便化疗。术后加强与小儿肿瘤内科联系,以提高长期无病生存率。