小儿恶性实体瘤雌激素受体

对６３例小儿常见恶性实体瘤石蜡切片进行雌激素受体（ＥＲ）酶联亲和组织化检测。ＥＲ阳性率睾丸内胚窦瘤为６０％（６／１０％），性腺外内胚窦瘤８０％（４／５），神经母细胞瘤６０％（９／１５），肾母细胞瘤２９％（４／１４），横纹肌肉瘤与非何杰金淋巴瘤为０（０／１１和０／６）。小儿恶性肿瘤ＥＲ检测对示肿瘤病因、指导内分泌治疗和鉴别诊断有一定意义。     

小儿常见恶性实体肿瘤耐药性分析

目的 通过对小儿常见的神经母细胞瘤、肾母细胞瘤、横纹肌肉瘤和恶性畸胎瘤的药敏检测,讨论各种常用化疗方案的治疗价值。方法 用17例肿瘤标本,其中神经母细胞瘤5例,化疗方案CCSG。肾母细胞瘤4例,化疗方案为DD方案。横纹肌肉瘤5例,CYVADIC:方案。恶性畸胎瘤3例,PVB方案。用流式细胞术荧光标记法,测定化疗药物敏感性。分析化疗疗效与耐药性。 结果 神经母细胞瘤对烷化剂类(CTX,IFO)、抗代谢药物(ACD)、VM26、TAL敏感性较高(P<0.05),化疗方案与药敏符合率约50％。肾母细胞瘤敏感的药物较多,化疗方案与药敏结果符合率约66.7％。以上两者疗效较好。横纹肌肉瘤耐药性较强。恶性畸胎瘤药敏对化疗方案符合率仪33_3％。两者疗效较差。结论 小儿实体恶性肿瘤现行化疗方案与肿瘤实际的药敏结果有一定的差距。用流式细胞仪测定肿瘤药物敏感性对预测化疗疗效及个体化化疗有指导意义     

PI3K／Akt信号通路与小儿恶性实体肿瘤研究进展

小儿恶性实体肿瘤包括神经母细胞瘤、肾母细胞瘤、肝母细胞瘤、横纹肌肉瘤等，是严重危害儿童健康的重要疾病之一。目前研究表明，细胞的存活、凋亡、分化或信号传导异常可能导致恶性肿瘤发生发展，其中以细胞信号传导异常尤为重要。已发现多条信号通路（如PI3K／Akt、MAPK通路，Ras途径等）与肿瘤关系密切，     

神经母细胞瘤,肾母细胞瘤的细胞培养在临床的应用

对我院手术切除的神经母细胞瘤6例、肾母细胞瘤14例的新鲜肿瘤标本及区域淋巴结（所取标本与病理标本等分）进行原代细胞培养。结果本组20例瘤体的细胞培养涂片检查与病理切片诊断一致。淋巴结细胞培养与病理切片诊断对照结果为：神经母细胞瘤病理切片阳性率33．3％，细胞培养阳性率50％；肾母细胞瘤病理切片诊断阳性率33．3％，细胞培养阳性率66．6％。可见常规的病理切片的局限性对于微小的转移灶，不一定被包含在片中而受到假阴性的影响，细胞培养可以弥补这一不足。     

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。     

肾母细胞瘤术前化疗疗效与耐药性

目的：探讨肾母细胞瘤术前化疗疗效规律及耐药性的生物学特性,确认其术前化疗的合适疗程。方法：选择15例按L化疗方案接受术前化疗5周以上,资料记录完整的患儿作为术前化疗疗效研究对象,测量术前化疗不同疗程肿瘤大小;对18例未术前化疗和经不同疗程术前化疗病理档案,采用JSD－单克隆抗体对肾母细胞瘤组织多药耐药蛋白（P-glycoprotein,P-gp)进行免疫组织化学检测,了解P－gp在术前化疗不同疗程的 表达特点。结果：术前化疗2周后,肿瘤体积缩小值最明显,术前化疗4周后,其体积缩小值减缓,部分病例有逐渐增大趋势;而术前化疗疗程越长,肿瘤细胞P－gp表达越强。结论：L术前化疗方案对肾母细胞瘤的疗效肯定,疗程以2－3周后最显著。其疗效降低可能与术前化疗后瘤组织对化疗药物耐药性明显增强有关。合适疗程为3－4周。     

凋亡抑制因子及血管内皮生长因子在儿童肾母细胞瘤中的表达及意义

目的研究凋亡抑制因子（survivin）及血管内皮生长因子（VEGF）在肾母细胞瘤中的表达及其临床意义。方法应用免疫组织化学SABC法及RT-PCR方法研究Survivin及VEGF在52例肾母细胞瘤组织，47例瘤旁组织及8例肾组织在蛋白水平及mRNA水平的表达情况。结果52例肾母细胞瘤组织中Survivin免疫组织化学显示阳性表达率为61．5％（32／52），RT-PCR阳性率为67．3％（35／52）；47例瘤旁组织中免疫组织化学显示阳性表达率为4．3％（2／47），RT-PCR阳性率为6．4％（3／47）；肾组织中未见表达。52例肾母细胞瘤组织中VEGF免疫组织化学显示阳性表达率为75．0％（39／52），RT-PCR阳性率为71．2％（37／52）；47例瘤旁组织中免疫组织化学显示阳性表达率为19．1％（9／47），RT-PCR阳性率为23．4％（11／47）；肾组织中免疫组织化学显示阳性表达率为12．5％（1／8），RT-PCR阳性率为25．0％（2／8）。另外，Survivin及VEGF在不良组织型肾母细胞瘤组织及瘤旁组织中表达均明显增高。Survivin及VEGF阳性者2年存活率均低于其表达阴性者。结论Survivin，VEGF表达与肾母细胞瘤的临床病理学特点有关，其与肿瘤血管的生成，血管内皮细胞的凋亡，稳定性密切相关，进而影响肿瘤的侵袭力。其检测有利于肾母细胞瘤的诊断及其预后情况的评价。     

静脉肾盂造影不显影的肾母细胞瘤

对临床怀疑肾母细胞瘤病例结合静脉肾盂造影（ＩＶＰ）及病理检查进行对照研究。ＩＶＰ显影者占４４．８％，Ｘ线诊断为肾母细胞瘤中，有２例病理诊断分别为成神经细胞瘤和畸胎瘤；ｌ例ＩＶＰ无异常者，病理诊断为肾母细胞瘤。ＩＶＰ不显影者占５５．２％，病理诊断均为肾母细胞瘤。对于小儿腹部实质性肿块，如果ＩＶＰ不显影，仍应考虑有肾母细胞瘤可能。     

小儿胰母细胞瘤的诊断和治疗

目的：介绍小儿胰母细胞瘤的诊断治疗经验。临床资料：手术病理诊断８例。年龄１～８岁。男６例，女２例。多以腹块（６／８）、腹痛（４／８）就诊。可误诊为腹膜后神经母细胞瘤、畸胎瘤及黄疸性肝炎。５例ＡＦＰ有轻～中度升高（２０．５６～５９８．８７μｇ／Ｌ），Ｘ线平片及ＣＴ均可见不同程度钙化。肿瘤部位：胰头３例、胰体３例、胰尾２例。局部切除５例、扩大切除（Ｗｈｉｐｐｌｅ术）１例、活检２例。术后分期：Ⅰ、Ⅱ期３例，Ⅲ期２例，Ⅳ期３例。组织学特点：分界清，略分叶，肉眼见有包膜，光镜下与胚胎期８周时的胰胚基相似。治疗结果：本组６例化疗者均生存，最长者已８年。１例Ⅲ期患儿活检后化疗肿瘤消失、ＡＦＰ降至正常，无瘤生存至今已４年。１例Ⅳ期患儿化疗３年至今带瘤生存。化疗药物以长春新碱、环磷酰胺、阿霉素为主，复发者加放疗及顺铂。结论：胰母细胞瘤影像学检查有非特异性钙化。血ＡＦＰ值可作为瘤标用于诊断及随访。肿瘤对化疗敏感，难以一期切除者活检后先化疗，再酌情施行根治性手术。其预后比成人胰母细胞瘤及胰腺癌要好，应积极治疗。     

肾母细胞瘤切除术中探查对侧肾脏是必须的吗?

目的：探讨肾母细胞瘤切除术中对侧肾脏探查的必要性。方法：1979年10月至1994年12月，共81例肾母细胞瘤患儿均于术前接受B超、CT和IVU检查，所有患儿均在本院接受手术并化和放疗。15例患儿接受了MRI成像检查。结果：76例患儿术前诊断和为单侧或双侧（仅3例）肾母细胞瘤，与手术结果完全一致，4例患儿术前怀疑为神经母细胞瘤，1例疑为畸胎瘤。3例双侧者均为小肿瘤侧半肾切除和大肿瘤侧全肾切除，单侧者均未探查对侧肾脏。术后病理证实为肾母细胞瘤。根据NWTS的分期标准，Ⅰ期34例，Ⅱ期23例，Ⅲ期15例，Ⅳ期6例，Ⅴ期3例，结果：78例单侧患儿随访6－20年，5年生存率为79．49％，患儿死于转移，复发和化疗或放疗并发症，无一例患儿发现有对侧肾母细胞瘤。结论：肾母细胞瘤切除术中无必要探查对侧肾脏。     

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".     

儿童胚胎性肿瘤微卫星不稳定性和杂合性缺失的研究

目的 探讨二种儿童胚胎性肿瘤--肾母细胞瘤和神经母细胞瘤中微卫星不稳定性(microsatellite instability,MSI)与杂合性缺失(loss of heterozygosity,LOH)的状态.方法 提取30例肿瘤组织及15例外周血DNA,选取14个微卫星位点(BAT125、BAT26、D2S119、D2s123、D2S136、D2S288、D2S367、D2S391、D3S1029、D3S1076、D3S1277、D3S1561、133S1611及D3S1612),用PCR扩增及变性聚丙烯酰胺凝胶电泳方法 检测微卫星不稳定性和杂合性缺失.结果 30例肿瘤标本中8例出现MSI,包括5例肾母细胞瘤和3例神经母细胞瘤.1例神经母细胞瘤出现LOH;队T25、D2S119、132S123、I)2S136、D2S288、132S391、D3S1076、D3S1277及D3S1611 9个位点的MSI阳性率分别为16.7%(5/30),14.3%(1/7),14.3%(1/7),14.3%(1/7).28.6%(2/7),28.6%(1/7),14.3%A(1/7),14.3%(1/7)和14.3%(1/7);D2S119、133S1029、D2S367、及D3S1611 4个位点的LOH阳性率均为14.3%(1/7).结论微卫星不稳定性和杂合性缺失现象存在于部分儿童胚胎性肿瘤中,提示此类肿瘤具有基因组不稳定性,DNA错配修复系统异常可能与其发生有关.     

Irinotecan for children with relapsed solid tumors

Irinotecan is expected to become a new drug for childhood solid tumors. Sixteen children with relapsed solid tumors received irinotecan 180 mg/m²/day for 3 consecutive days, repeated once after 25 days off. Their original tumors were neuroblastoma in 7, rhabdomyosarcoma in 3, nephroblastoma and undifferentiated sarcoma in 2 each, and primitive neuroectodermal tumor and leiomyosarcoma in 1 each. The average age at trials was 6 years. Partial response was achieved in 5 (31.3%) (neuro-blastoma, rhabdomyosarcoma, nephroblastoma, undifferentiated sarcoma, and leiomyosarcoma), and decrease in tumor marker in the other 2. Irinotecan appears promising, and could become included in the first-line treatment.     

KAI1/CD82表达水平与肾母细胞瘤转移的相关性研究

目的探讨KA儿/CD82与肾母细胞瘤转移的相关关系。方法选取38例确诊为肾母细胞瘤的组织蜡块标本,按有无转移分为两组,采用免疫组织化学的方法检测KAI1/CD82的表达。结果肾母细胞瘤中无转移组和有淋巴结或远处转移组的KAI1/CD82阳性表达率分别为53.85%、33.33%,两者差异有统计学意义;Ⅰ、Ⅱ、Ⅲ、Ⅳ期肾母细胞瘤中,KAI1/CD82阳性表达率分别为62.50%、58.33%、33.33%、33.33%,各组间差异无统计学意义。无转移组和有淋巴结或远处转移组中,化疗组与未化疗组分别比较,差异均无统计学意义(P0.05)。结论肾母细胞瘤中KAI1/CD82的阳性表达率与肿瘤是否转移有关,与临床分期及术前是否化疗无关。     

采用交替或多药联合化疗治疗晚期神经母细胞瘤

目的：观察交替化疗与多药联合化疗治疗晚期儿童神经母细胞瘤的疗效,毒性反应及对生存期的影响。方法：对29例晚期神经母细胞瘤的患儿给予术前或术后化疗,14例采用COAVIP或VP方案交替化疗共155疗程,15例采用COPE等多药联合化疗共84疗程。结果：交替化疗组14例可评价疗效13例,CR0,PR12例,NC1例,PD0。有效率12／13（92．3％）。化疗后手术完整切除率10／13（76．9％）。多药联合化疗组15例,可评价疗效11例,CR1例,PR5例,NC3例,PD2例,有效率6／11（54．5％）。化疗后手术切除率为5／11（45．5％）。两组比较P＜0．05（X^2检验）,化疗的毒性反应主要表现为骨髓抑制,恶心呕吐等,均为可逆尾。两组生存期比较经秩和检验P＞0．05无统计学差异。结论：交替化疗较之多药联合化疗治疗晚期儿童神经母细胞瘤疗效好,手术切除率高。毒性反应大致相同,两组生存期也大致相同。     

维生素A对大鼠肾母细胞瘤发生影响的实验研究

目的 通过对Wistar幼鼠维生素A（Vit A)缺乏饮食组和正常饮食组对1，2－二甲基肼（1，2－dimethylhydrazine,DMH)所诱导的肾母细胞瘤成瘤率和肾源性剩余（nephrogenic rest,NR)检出率的比较，证实维生素A对肿瘤形成的影响，以及肾源性剩余在肾母细胞瘤发生中的作用。方法 建立DMH诱导的Wistar幼鼠的肾母细胞瘤动物模型，将其分成二组，分别给予正常饮食和维生素A缺乏饮食。1年内观察肿瘤生成和肾源性剩余形成情况。结果 30只正常饮食组检出肾母细胞瘤4只，占13.3%(4/30)，NR数为2只，占3.3%(2/60)。30只Vit A缺乏饮食组，检出肾母细胞瘤11只，占36.7%(11/30)，NR数10只，占16.7%(10/60)。两组成瘤率和NR检出率相比（χ^2检验）差别有显著性意义（P＜0.05)。结论 Vit A在肾母细胞瘤的发生中起了重要的作用，其缺乏状态可能与肾胚基细胞的分化停止或迟滞有关。     

p53 mutations and loss of p53 function confer multidrug resistance in neuroblastoma

BACKGROUND: Neuroblastomas often acquire sustained drug resistance during therapy. Sensitivities to carboplatin, etoposide, or melphalan were determined for 18 neuroblastoma cell lines; eight were sensitive and ten were resistant. As p53 mutations are rare in neuroblastomas studied at diagnosis, we determined if acquired p53 mutations and loss of function conferred multidrug resistance. RESULTS: Loss of p53 function (p53-LOF), defined as a failure to induce p21 and/or MDM2 in response to melphalan, was seen in 1/8 drug-sensitive and 6/10 drug-resistant cell lines. In four cell lines p53-LOF was associated with mutations in the DNA binding region of p53, while three cell lines with LOF and four cell lines with functional p53 had no evidence of p53 muta-tions. Nonfunctional and mutated p53 was detected in one resistant cell line, while a sensitive cell line derived from the same patient prior to treatment had functional and wild type (wt) p53. We transfected HPV 16 E6 (which mediates degradation of p53, causing LOF) into two drug-sensitive neuroblastoma cell lines with functional p53. LC(90) values of HPV 16 E6 transfected cell lines were 3-7-fold (melphalan), 8-109-fold (carboplatin), and 2-158-fold (etoposide) greater than that of LXSN-transfected controls. CONCLUSIONS: These data suggest that some neuroblastomas acquire p53 mutations during therapy, which is associated with a loss of p53 function, and can confer high-level multidrug resistance.     

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.     

Beckwith-wiedemann syndrome and neural crest tumors

We report 2 cases of thoracic neural crest tumors complicating the course in patients with Beckwith-Wiedemann syndrome (BWS). In the first patient, a thoracic neuroblastoma was fortuitously discovered at age 3 months on a chest film prior to a partial glossectomy. In the follow-up left nephroblastoma and a right kidney simple cyst appeared. In the second patient, a thoracic tumor which proved to be a mature ganglioneuroma was discovered at age 4 years on a follow up spinal radiograph. Although less frequent than nephroblastoma and/or adrenal tumors, the occurrence of thoracic neuroblastoma in BWS suggests that periodic chest radiograph and assays of HVA, VMA and Dopamine should be included in the follow-up protocol.