术前化疗治疗神经母细胞瘤的疗效随访及其影响因素

目的探索术前化疗治疗神经母细胞瘤患儿的远期疗效及对其生存的影响因素。方法对１３例经术前化疗后手术的病例进行２～６年的疗效随访，分析存活组与死亡组的临床分期、化疗时间、香草杏仁酸（ＶＭＡ）、病理标本增殖细胞核抗原（ＰＣＮＡ）、ＤＮＡ指数的差异。结果２年生存率为６９％（６／１３），５年生存率为２３％（３／１３），６例（４６％）无瘤生存至今。存活组化疗后ＶＭＡ、ＰＣＮＡ、ＤＮＡ指数较死亡组明显下降（Ｐ均＜０．０５）。结论术前化疗可以提高晚期神经母细胞瘤远期疗效和生存率，化疗后肿瘤增殖活性的抑制程度与临床疗效密切相关。     

16例双侧肾母细胞瘤的危险因素分析

目的 分析双侧肾母细胞瘤的危险因素。方法 用Kaplan-Meier生存分析方法对我院从1960～2002年收治的16例双侧肾母细胞瘤进行生存时间研究。结果 是否伴发畸形、是否术前化疗、病理分型为影响双侧肾母细胞瘤生存的危险因素；本组病例五年生存率为37．05％。结论 伴发畸形的双侧肾母细胞瘤预后较差。术前常规化疗是提高双侧肾母细胞瘤长期生存率的重要因素。根据组织学类型和临床分期，严格按照NWTS-5的标准，以使治疗个体化，是提高双侧肾母细胞生存率的重要因素。     

骨骼化血管提高儿童晚期神经母细胞瘤延期一期手术切除率

目的晚期神经母细胞瘤（Ⅲ～Ⅳ期）风险高，手术切除率低，直接影响治疗和预后。本文探讨提高儿童高风险神经母细胞瘤延期一期手术切除率的方法。方法对22例儿童高风险神经母细胞瘤予术前化疗，肿瘤有所缩小后手术，从正常部位血管-髂血管解剖入手，对腹膜后受肿瘤包裹、侵犯的大血管进行骨骼化处理，手术切除，并对结果进行分析。结果22例中，21例完全切除肿瘤，占95．45％，显著高于文献报道完全切除率，且无严重并发症及围手术期死亡病例。结论通过合适的手术方法，对腹膜后大血管行骨骼化处理，能够显著提高神经母细胞瘤延期一期手术完全切除率，且并发症少。     

肾母细胞瘤术前化疗方案及手术时期的选择评价

目的探讨肾母细胞瘤术前化疗与手术时期的选择。方法肾母细胞瘤患儿57例，男41例，女16例；年龄2个月。11岁，平均年龄6．3岁；因腹部肿块就诊43例，肉眼血尿就诊14例；肿瘤越过中线39例；排除化疗前即存在恶病质、肿瘤侵犯大血管及远处转移病例。所有病例随机分为标准化疗组与改良化疗组，标准化疗组26例，术前按全国推荐方案进行2个疗程的化疗；改良化疗组31例，实施1个疗程化疗方案。结果标准化疗组与改良化疗组全瘤切除率分别为69．2％、93．5％。结论术前化疗可有效提高肾母细胞瘤患儿术后存活率，但全瘤切除是保障患儿长期存活的基本条件，术前化疗与手术时期的选择对肾母细胞瘤患儿无瘤存活率具有重要意义。     

神经母细胞瘤综合治疗

目的 探讨神经母细胞瘤的综合治疗方法。方法 分析日本松户市立医院24例神经母细胞瘤的治疗效果。早期神经母细胞瘤，即1岁未满的病例和Ⅰ期、Ⅱ期、Ⅳs期的病例共13例，10例是由筛查发现。岛田分类10例是预后良好型，2例预后不良型；遗传因子N-myc扩增11例阴性。晚期神经母细胞瘤，即1岁以上的Ⅲ期、Ⅳb期和全年龄的Ⅳa期患者，共11例；岛田分类3例预后不良型；N-myc扩增2例阴性，1例10倍以上扩增；2例进行了末梢造血干细胞移植（PBSCT）。晚期患者诊治按照日本厚生省晚期神经母细胞瘤的综合诊疗方案进行。结果 13例早期神经母细胞瘤患者均Ⅰ期完成肿瘤切除术，经不同的术后化疗，全部临床缓解或治愈，生存率100％。晚神经母细胞瘤11例，10例患者在化疗2-4个疗程后进行了Ⅱ期肿瘤切除，淋巴结清除术，5年生存率为36.2％。结论神经母细胞瘤早期病例可通过手术切除、简单化疗而治愈。晚期病例，通过手术、化疗和放疗，配合造血干细胞移植等，可提高生存率。     

手术完全切除肿瘤对晚期神经母细胞瘤患儿生存率的影响

目的分析21例Ⅲ期、Ⅳ期腹膜后神经母细胞瘤患儿经血管骨骼化方法完全切除肿瘤后的临床疗效,探讨手术完全切除肿瘤对晚期神经母细胞瘤患儿生存率的影响。方法2003年至2008年,对本院收治的22例临床诊断为Ⅲ期、Ⅳ期神经母细胞瘤的患儿,经穿刺活检病理诊断明确为神经母细胞瘤后,按照最新国际标准化疗方案行4～6个疗程的化疗,待肿瘤体积缩小后,采用腹膜后大血管骨骼化的方法实施手术,21例完全切除肿瘤,并继续化疗等治疗。通过门诊复查及电话、信件随访的方式了解术后康复情况,包括有无原位复发、有无远隔转移、是否存活以及死亡原因等。结果21例延期一期手术完全切除肿瘤（占95．45％）,无严重的术后并发症及围手术期死亡。失访3例。随访病例中,无瘤存活10例,占55．56％;带瘤存活3例,占16．67％;死亡5例,占27．78％,5年总体生存率为72．22％（13／18）。结论通过腹膜后大血管骨骼化方法完全切除儿童Ⅲ期、Ⅳ期神经母细胞瘤,能显著提高术后生存率。     

胚胎干细胞基因Oct-4在神经母细胞瘤组织中的表达及意义

目的 探讨神经母细胞瘤组织中胚胎干细胞基因Oct-4的表达情况及其意义.方法 收集39例神经母细胞瘤和相应癌旁组织,应用实时定量PCR和Western印迹法检测Oct-4的表达,并分析其表达与临床病理参数的相关性.结果 术前未化疗的神经母细胞瘤Oct-4的mRNA相对表达量为6.53±1.74,明显强于瘤旁组织1.04±0.65,两组间差异有统计学意义(P＜0.05);其中Ⅲ～Ⅳ期肿瘤Oct-4 mRNA相对表达量8.81±0.67较Ⅰ～Ⅱ期肿瘤4.26±0.54高,差异有统计学意义(P＜0.05).Ⅲ～Ⅳ期肿瘤中术前未化疗的Oct-4 mRNA相对表达量8.81±0.67明显高于术前化疗的肿瘤3.15±0.42(P＜0.05).神经母细胞瘤Oct-4表达与患儿性别、年龄、肿瘤大小、肿瘤部位、病理分型等参数无相关性.结论 Oct-4可能与神经母细胞瘤的发生、发展相关,化疗药物的使用对其表达有抑制作用.     

Ⅲ,Ⅳ期神经母细胞瘤的外科处理：延期和二次手术

应用延期和二次手术治疗Ⅲ、Ⅳ期神经母细胞瘤１２例。术前化疗时间平均３．７９±２．０９月，ＣＴＸ化疗强度（ＤＩ）７３１．５±３５６．７ｍｇ·（ｍ￣２）￣（－１）／周。肿瘤切除率８３．３％，显著高于一期手术组（Ｐ＜０．０１）。重点探讨延期和二次手术的指征、时机和临床意义，强调延期和二次手术对Ⅲ、Ⅳ期神经母细胞瘤疗效提高和长期生存的积极作用。     

小儿纵隔交感神经源性肿瘤18例报告

本文报道自1964～1982年收治的18例小儿纵隔交惑神经源性肿瘤(神经母细胞瘤12例,神经节母细胞瘤4例,神经节细胞瘤2例),均位于后纵隔。呼吸道及神经压迫为常见症状,术前出现Horner征预示恶性。手术切除12例,本组神经母细胞瘤五年生存率25%。未行手术、单用化疗及Ⅲ、Ⅳ期病例均死亡。生存者均为2岁以下,Ⅰ、Ⅱ期和肿瘤全部切除的病例。强调早期手术,术后坚持化疗和放疗可提高生存率。神经母细胞瘤因具有自然消退特性,不能轻易放弃治疗。     

小儿肾母细胞瘤、神经母细胞瘤肿瘤组织培养的临床应用

目的：对比组织法与病理切片在肿瘤淋巴结转移的阳性率。方法：对14例肾母细胞瘤、6例神经母细胞瘤进行肿瘤组织、淋巴组织瘤旁培养，涂片进行病理诊断、并与传统的病理切片对比，结果：肿瘤组织培养与病理切片结果完全一致。对区域淋巴结转移的诊断，淋巴结组织培养优于病理切片，两者淋巴结转移的阳性率，肾母细胞瘤为66．6％（6／9）和33．3％（3／9）；神经母细胞瘤为50％（3／6）和33．3％（2／6），结论：淋巴结组织培养对肿瘤淋巴结转移的诊断率高于病理切片，对临床分期、治疗及预后判断具有重要的指导意义。     

Neuroblastoma preoperatively treated as nephroblastoma: does inadequate therapy worsen the prognosis?

BACKGROUND: The current standard in the treatment of nephroblastoma is preoperative chemotherapy based on radiological appearance. After subsequent surgical removal few tumours proved histologically to be neuroblastoma. We asked whether initial chemotherapy according to nephroblastoma trials would change the prognosis for those neuroblastoma patients. RESULTS: Out of 1603 patients registered in the German neuroblastoma trials, 29 patients (1.8 %) have preoperatively been treated according nephroblastoma protocols. Advanced stages (11 stage 3, 12 stage 4) were dominant. Diagnostic work up of those patients revealed elevation of catecholamine metabolites in only 39 % (compared to 80 % of the control patients) and mIBG uptake in only 71 % (compared to 89 % of the control patients). Elevation of NSE was observed in 92 % of patients (control group 72 %). Patients with preoperative nephroblastoma treatment were older than the patients of the control group. Risk factors like MYCN amplification or elevation of LDH were more often detected. The outcome of the patients with preoperative chemotherapy according nephroblastoma trials was worse than that of the control group, but risk group adapted survival analysis revealed no disadvantage. CONCLUSION: The prognosis of children with neuroblastoma tumours, which have been radiologically classified as nephroblastoma, is inferior compared to the prognosis of patients without preoperative nephroblastoma therapy. The difference appears to be associated rather with more unfavourable biology than with the element "preoperative chemotherapy".     

Complete surgical resection plus chemotherapy prolongs survival in children with stage 4 neuroblastoma

The factors that affect survival in patients with stage 4 neuroblastoma vary. Several prospective and retrospective studies have provided conflicting conclusions regarding the benefit of combining aggressive chemotherapy with complete surgical resection. We analyzed our experience to evaluate the effect of complete surgical resection of the primary tumor on survival when disseminated disease has been controlled by chemotherapy. We retrospectively reviewed the medical records of 44 consecutive children with neuroblastoma treated between 1990 and 2000. Twenty-six children with stage 4 disease were enrolled. Most were treated with surgical resection combined with chemotherapy. The survival rate was compared based on the timing (primary versus delayed until chemotherapy had been given) and results of surgery (complete tumor resection, microscopic residual disease, and gross residual disease). The mean survival (52.8 months) of children with delayed complete surgical resection (CSR) was statistically superior to that of those with microscopic residual (20.8 months, p=0.0111) or gross residual tumor (12.2 months, p=0.0141). In the CSR group, 1-, 2-, 3-, and 5-year survival rates were 88%, 77%, 77%, and 65%, respectively, vs. 80%, 40%, 20%, and 0% in the microscopic residual group. In conclusion, complete resection of the primary tumor with no residual disease was associated with improved survival in children with advanced neuroblastoma whose metastatic disease had been controlled by chemotherapy.     

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??Objective??To summarize the efficacy and safety of arsenic trioxide combined with chemotherapy for children with recurrent/refractory neuroblastoma. Methods??Retrospective analysis was made in seven cases of neuroblastoma treated with traditional chemotherapy combined with venous arsenic trioxide after diagnosis with poor prognosis or the condition deteriorated. Results??Among the seven patients treated with chemotherapy combined with venous arsenic trioxide for 3 to 7 courses??4 were effective and 3 were ineffective. Patient 3 was treated with arsenic trioxide combined with following regimen after tumor was not resected totally??and patient 5??6 and 7 were given arsenic trioxide combined with preoperative chemotherapy. Patient 3 and patient 5 achieved complete remission after combination chemotherapy??and patient 6 and patient 7 showed decreased tumor volume and tumor marker. Patient 1??2 and 4 were given arsenic trioxide after failure of conventional chemotherapy. Metastasis in patient 1 disappeared at first??but the disease relapsed after 11 months. The tumor responded poorly and increased in size and number in patient 2 and patient 4. Patient 1 the use of arsenic trioxide was stopped in patient 1 because of prolonged QT interval??0.51s????who returned normal after symptomatic treatment. Five patients are still alive and they have lived for 3.5 y??3.0 y??1.2 y??1.0 y and 0.7 y??respectively. Conclusion??Venous arsenic trioxide combined with chemotherapy can be a choice of treatment for recurrent/refractory neuroblastoma??whose effect and safety requires further investigation.     

A 23-year experience with malignant renal tumors in infancy and childhood.

A retrospective analysis of 77 children treated between 1974 and 1996 was undertaken to evaluate morbidity and the evolution of therapy. A Wilms' tumor (WT) was present in 73 children. 74% of patients (pats.) with WT survived (54 of 73 pats.). Histological specimens of 67 patients were re-evaluated, including 4 children with non-WT histology. Among patients with Wilms' tumors (WT), nephroblastoma (NB) of intermediate risk predominated (73%; 46 of 63 pats.). Low-risk tumors occurred in 5 of 63 children (8%; mesoblastic nephroma 3, cystic partially diff. NB 1, completely necrotic NB 1). High-risk WT were diagnosed in 12 of 63 patients (19%) (NB with anaplasia 10, clear cell sarcoma 1, malignant rhabdoid tumor 1). Nephrogenic rests were present in 14 cases. We observed 3 children of school age with renal carcinoma and one patient with an intrarenal neuroblastoma. WT histology was the most important factor determining prognosis (p = 0.018). The risk for relapses was 2.6-fold higher in patients with high-risk WT compared to the standard risk group. Stages were re-evaluated according to SIOP 93-01. Comparing relapse-free survival of stages I, II and III, respectively, there was a reduced survival rate for stage III (p=0.019). According to the SIOP/GPOH protocol in 1989, the regimen was switched from primary surgery to preoperative chemotherapy without biopsy in 1989 (11 pats.). Compared to earlier years, survival improved (n.s.). In 3 patients preoperative diagnosis by means of imaging failed. During preoperative chemotherapy a venous occlusive disease of the liver occurred in 2 patients. Preoperative chemotherapy led to an impressive tumor shrinkage in the majority of patients. 2 patients of the preoperative group died (focal anaplastic NB). Long-term morbidity was analysed in 49 patients and included radiation-induced scoliosis (35), chest-wall deformity (3), congestive cardiomyopathy after relapse (1) and arterial hypertension (2). Over the years there was a trend to reduce frequency and dose of irradiation. Prognosis of WT is excellent but unfavorable histology (high risk) predicts a poor prognosis. In our experience, reduction of tumor volume due to preoperative chemotherapy facilitates tumor removal by surgery and may prevent tumor spillage and the deleterious effects of radiation in young children. Surgery without delay is necessary if the diagnosis is unclear or the tumor fails to respond to preoperative chemotherapy.     

Surgical complications in the treatment of Wilms' tumor.

We present our data on the treatment of Wilms' Tumor (WT) with an emphasis on both the positive effect and the adverse effect of preoperative chemotherapy with regard to surgical intervention. From 1980 to 2000 70 children were treated. 57 % received preoperative chemotherapy (ChTx) and 43 % were operated on primarily. 75 % of the tumors responded to ChTx with significant shrinkage of the size. After preoperative ChTx 54 % of the cases were regrouped as stage I, whereas after primary operation 46 % of the patients were grouped as stage I, thus indicating a downstaging with preoperative ChTx. In 8 % of the patients with preoperative chemotherapy intraoperative complications occurred with a rupture of the tumor in 1 case. In contrast, there were intraoperative complications in 25 % of the patients with a primary operation with rupture of the tumor in 3 cases. 1 child (1.5 %) was treated with chemotherapy who did not have a Wilms' tumor but a benign nephroma (CMN). 3 cases had a clear cell sarcoma (CCSK) and in one case histology revealed a rhabdoid tumor (MRTK). In one case of CCSK only histology of the metastases disclosed the correct diagnosis. The rate of postoperative complications such as ileus was the same for both groups. Irrespective of the known adverse effects such as changing tumor histology, which may affect the correct staging, and the remaining risk of an initial inadequate treatment, our data show that the regimen of preoperative chemotherapy as proposed by the SIOP study should not be abandoned. However, the relatively small number of our patients does not allow a significant statement to be made but confirms the results of past SIOP studies.     

晚期儿童神经母细胞瘤的临床和预后分析

目的：探讨晚期儿童神经母细胞瘤的临床特点、治疗策略和预后。方法：对63例确诊为III～IV期的神经母细胞瘤患者的临床资料进行回顾性分析,有60例患者接受了手术切除和（或）化疗和（或）局部放疗,其中14例患者还接受了自体外周血造血干细胞移植治疗。结果：63例患者中,男女比例为2.7∶1,中位年龄4岁;常见首发症状为发热、腹痛、腹部肿块、腿痛或关节疼痛;常见原发部位为肾上腺（38%）、腹膜后（35%）、后纵隔（17%）、盆腔（6%）和颈部（2%）;确诊时常见转移部位为局部（41%）和（或）远处（37%）淋巴结、骨髓（60%）、骨（46%）、肝脏（16%）。中位生存时间32.7个月,2年生存率44.3%。年龄>1岁（P<0.05）、血清神经元特异性烯醇化酶>100 mg/L（P<0.05）、血清乳酸脱氢酶>1 500 U/L（P<0.01）、血清铁蛋白>150 mg/L（P<0.05）是预后不良指标。完整切除原发肿瘤可延长患者总体生存时间（P<0.05）;强烈化疗联合自体外周血造血干细胞移植的综合治疗可延长患者总体生存时间（P<0.01）。结论：晚期儿童神经母细胞瘤临床表现多样,预后差,熟悉其临床和实验室检查特点尽早明确诊断、完整切除原发肿瘤、进行自体外周血造血干细胞移植支持下的强烈化疗的综合治疗有利于改善预后。［中国当代儿科杂志,2007,9（4）：351-354］     

术前多基因联合检测指导化疗对进展期神经母细胞瘤儿童手术切除率及预后的影响

目的 探索术前多基因联合对进展期神经母细胞瘤(NB)患儿手术切除率及预后的影响.方法 收集2013年1月至2015年l月本院收治的采取手术治疗的进展期(Ⅲ、Ⅳ期) NB 患儿 46例,均经病理确诊.根据INSS 分期及COG危险度分层,本组病例Ⅲ期 19 例 (41.3%) ,Ⅳ期 27 例 (58.7%) ,中危15例(32.6%),高危31例(67.4%).46例患儿均行术前新辅助化疗及手术治疗.依据术前是否行多基因联合检测分为多基因联合检测化疗组和常规化疗组.多基因联合检测组患儿,根据药敏结果参考选择化疗方案,如常规方案中有一种药物敏感,则可选择该方案进行化疗.如常规方案中无敏感药物或化疗两个疗程后评估提示化疗效果欠佳,则根据药敏结果选用包含至少一个敏感药物的化疗方案.结果 3例ERCC阴性中危患者最初使用方案无铂类药物,肿瘤缩小不满意,后根据药敏检测更换包含铂类药物方案后肿瘤缩小明显,均在更换方案后2~3个疗程行手术,其余4例中危患儿均提示TOPOIIα高表达,选用了OPEC方案及卡铂+足叶乙甙/阿霉素轮换.高危患儿中5例TOPOI阴性患儿最初均使用CT方案,第二或三个疗程时根据药敏结果换用OPEC方案.其余患儿检测结果提示对铂类、足叶乙甙或蒽环类其中之一敏感,使用OPEC方案化疗.多基因联合检测组术前化疗3~6个疗程,平均 4.6个疗程,常规化疗组术前化疗4~8个疗程,平均 5.6个疗程.多基因联合检测组患儿肿瘤瘤体缩减率明显高于常规化疗组.两组患儿手术切除率差异无统计学意义.本资料所有患儿均获得随访,随访时间14~30个月,平均21个月,总体生存率为60.9%,中危组患儿2年生存率为80%,高危组期患儿2年生存率51.6%.多基因联合检测化疗组2年生存率为中危85.7%,高危53.8%,总生存率为65%,常规化疗组2年生存率为中危75%,高危50%,总生存率为57.7%.两组相比差异无统计学意义.结论 进展期神经母细胞瘤患儿联合检测ERCC1、TOPOI 和TOPOIIα表达指导个体化化疗,有效率有所提高,化疗不良反应减少,改善了患儿生活质量.     

Primary tumor control in patients with stage 3/4 unfavorable neuroblastoma treated with tandem double autologous stem cell transplants

OBJECTIVE: To assess the efficacy and toxicity of local radiotherapy in achieving local control in patients with stage 4 or high-risk stage 3 neuroblastoma treated with induction chemotherapy and tandem stem cell transplants. METHODS: Fifty-two children with stage 4 or high-risk stage 3 neuroblastoma were treated on a standardized protocol that included five cycles of induction chemotherapy, surgical resection of the primary tumor when feasible, local radiotherapy, and then consolidation with tandem myeloablative cycles with autologous peripheral blood stem cell rescue. Local radiotherapy (10.5-18 Gy) was administered to patients with gross or microscopic residual disease prior to the myeloablative cycles. Thirty-seven patients received local radiotherapy to the primary tumor or primary tumor bed. Two patients with unknown primaries each received radiotherapy to single, unresectable, bulky metastatic sites. The second of the myeloablative regimens included 12 Gy of total body irradiation. RESULTS: Of the 52 consecutively treated patients analyzed, 44 underwent both transplants, 6 underwent a single transplant, and 2 progressed during induction. Local radiotherapy did not prolong recovery of hematopoiesis following transplants, did not increase peritransplant morbidity, and did not prolong the hospital stay compared with patients who had not received local radiotherapy. Local control was excellent. Of 11 patients with disease recurrence after completion of therapy, 9 failed in bony metastatic sites 3 to 21 months after the completion of therapy, 1 recurred 67 months following therapy in the previously bulky metastatic site that had been irradiated, and 1 had local recurrence concurrent with distant progression 15 months following the second transplant. The three-year event-free survival was 63%, with a median follow-up of 29.5 months. The actuarial probability of local control was 97%. CONCLUSIONS: The use of induction chemotherapy, aggressive multimodality therapy for the primary tumor, followed by tandem myeloablative cycles with stem cell transplant in patients with stage 4 or high risk stage 3 neuroblastoma has resulted in acceptable toxicity, a very low local recurrence risk, and an improvement in survival.     

Clinical Experiences in the Treatment of Neuroblastoma with 131I-Metaiodobenzylguanidine

Treatment of neuroblastoma is an unsolved problem of pediatric oncology. In spite of highly intensified chemotherapy, the long-term survival rate of children with a metastatic neuroblastoma is below 10%. We therefore used ¹³¹I-metaiodobenzylguanidine (MIBG) for the first time to treat children with a neuroblastoma in relapse or primary unresponsiveness to chemotherapy. We had previously demonstrated that MIBG is useful for the scintigraphic imaging of neuroblastoma lesions and had investigated the cytotoxicity and uptake of MIBG in various neuroblastoma cell lines. We treated 6 children with neuroblastoma in a total of 19 courses. Three of the children suffered from a relapse of neuroblastoma; 3 had never gained a remission. Four of the 6 children lost their bone pain and fever during the first 3 days. In 5 of the 6 children the solid tumor as well as the bone marrow infiltration responded to MIBG treatment, with responses ranging from transitory decrease of the tumor mass to complete disappearance of abdominal tumors. We also witnessed a stabilization of osteolytic lesions, a decrease in elevated serum catecholamines, and a decrease in bone marrow infiltration. Five of the 6 children died of tumor progression 55-249 days after the first MIBG treatment.