儿童神经母细胞瘤染色体分析

目的总结55例神经母细胞瘤（NB）患儿的染色体结果,分析与临床特点及近期治疗效果的关系,提高对伴有染色体异常NB的认识。方法回顾性分析55例NB患儿的临床资料,包括分期分组、肿瘤标记物、染色体结果、治疗方案及近期预后情况。结果55例NB患儿中有4例存在17q获得（7％）,1例患儿同时存在17q获得及1 p缺失（2％）,余50例（91％）患儿染色体检查均正常。伴有染色体异常的5例患儿肿瘤标记物在病初均有不同程度的增高,而且血神经元特异性烯醇化酶（NSE）高于染色体正常组;5例染色体异常患儿均为Ⅳ期、高危组,均伴有MYCN基因获得,其中1例在治疗过程中失访,余4例中有2例肿瘤进展,1例死亡,1例经化疗联合手术切除及自体造血干细胞移植,门诊随访33个月疾病稳定。结论结果提示染色体1 p缺失和17q获得可能是NB的预后不良因素,染色体异常在NB的诊断及预后评估中具有一定临床指导意义。但本研究中的异常染色体检出率偏低,考虑与常规检测的误差有关,方法学有待进一步改进。     

神经母细胞瘤4S期预后不良相关因素的研究进展

神经母细胞瘤(neuroblastoma, NB)是儿童常见的颅外恶性实体肿瘤,国际神经母细胞瘤分期系统(International Neuroblastoma Staging System, INSS)将NB分为Ⅰ～Ⅳ期和Ⅳs期,其中Ⅳs(或4S)期是NB的一个特殊分期,以高转移率和高自愈率为主要特点。临床上4S期NB总体预后较好,患儿5年总体生存率为84%～92%,5年无事件生存率约82%。但仍有少部分4S期NB患儿预后不佳,此类患儿往往伴有不利的预后因素,如MYCN基因扩增、染色体畸变等,本文将阐述4S期NB预后不良相关因素的研究进展。     

儿童神经母细胞瘤骨髓微小残留病变的临床意义分析

目的探讨儿童神经母细胞瘤(NB)患者骨髓微量NB细胞的动态变化及其与临床特征、治疗转归的关系。方法纳入33例确诊为NB并完善骨髓微量NB细胞监测的患儿,采用流式细胞仪(FCM)检测NB患儿治疗前后骨髓微量NB细胞,结合临床数据,进行Mann-Whitney U tests及Fisher精确概率法分析。结果 (1)初诊时骨髓转移与INRG分期、MYCN扩增状态、治疗疗效及是否复发均无显著相关性。(2)转移期患儿的骨髓转移发生率为69%,提示骨髓是NB肿瘤细胞主要转移地点。(3)治疗后骨髓微小残留病灶(MRD)持续阳性或由阴转阳患儿复发可能性大(P 0.001)。结论本研究初诊转移期患儿转移发生率过半,提示NB侵袭性强,骨髓为主要转移器官。监测骨髓MRD有助于早期发现疾病复发,指导临床治疗。     

伴染色体17q获得的神经母细胞瘤3例临床分析

目的探讨伴染色体17q获得的神经母细胞瘤(NB)的临床特点及预后。方法回顾性分析我中心同期诊治的3例伴染色体17q获得的NB患儿的临床特征和近期治疗效果。NB患儿的诊断标准、肿瘤分期、临床危险度分组、治疗方案和疗效标准均根据北京儿童医院NB方案(BCH-NB-2007方案)。随访到2012年5月31日。应用FISH方法进行肿瘤组织细胞遗传学检查。结果 3例患儿确诊年龄均>18个月,病程1～6个月。原发瘤灶位于腹膜后或肾上腺,伴广泛转移,如淋巴结、骨髓、多部位骨骼转移等。INSS分期均为Ⅳ期,属高危组。3例患儿的原发瘤灶均存在染色体17q获得,无N-myc基因扩增及染色体1p缺失。均按高危NB方案治疗,1例于治疗5个月出现肿瘤进展,表现为发热、骨痛,放弃治疗。另外2例随访9个月和4个月,未见肿瘤进展或新发瘤灶。结论染色体17q获得的NB临床表现呈高度恶性,广泛转移。染色体17q获得可能与其它临床危险因素共同影响NB预后。     

基于美国儿童肿瘤学组方案治疗68例神经母细胞瘤的中长期随访结局

目的基于美国儿童肿瘤学组(COG)危险度分级的化疗方案,探讨神经母细胞瘤(NB)患儿诊断年龄与预后的相关性。方法以2007年1月至2013年3月复旦大学附属儿科医院外科诊断为NB的连续病例为研究对象,划分低危、中危和高危,分析不同INSS分期NB患儿的5年总体生存率和5年无事件生存率(EFS),并对诊断年龄和5年EFS行受试者工作特征(ROC)曲线分析,获得与EFS相关的最佳诊断年龄界值。结果 68例NB患儿进入分析,男41例(60.3%),女27例;Ⅰ期7例(10.3%),Ⅱ期14例(20.6%),Ⅲ期11例(16.2%),Ⅳ期23例(33.8%),Ⅳs期13例(19.1%)。低危24例,中危14例,高危30例。128例高危患儿术前行诱导化疗,非常好的部分缓解率为60.7%(17/28),部分缓解率为14.3%。60/68例接受手术治疗,肉眼完整切除(GTR)率为71.7%。28例失访,32例随访至5年,5年总体生存率为65.6%,其中Ⅲ期为66.7%,Ⅳ期为22.2%;5年EFS为59.4%,其中Ⅲ期为50.0%,Ⅳ期为11.1%,GTR患儿5年EFS高于未GTR患儿(70.2%vs 57.4%)。35/30例MYCN基因扩增阳性(Ⅱ期1例,Ⅳ期4例),2年总体生存率为40%(2/5),2年EFS为20%(1/5);25例MYCN基因阴性患儿,2年总体生存率为92%(23/25),2年EFS为88%(22/25)。4诊断年龄和5年EFS的ROC曲线下面积为0.713,诊断年龄2.4岁时的敏感度为75.0%,特异度为66.7%。结论采用COG治疗方案的Ⅳ期患儿的5年总体生存率为22.2%,5年EFS为11.1%。GTR与NB的预后相关,诊断年龄2.4岁可能提示预后不良。     

伴有MYCN基因扩增的神经母细胞瘤133例病例系列报告

背景：伴有MYCN基因扩增的神经母细胞瘤（NB）患儿的长期生存率不容乐观,目前国内相关大宗病例报道不多。 目的：总结伴有MYCN基因扩增的NB患儿的临床特征、治疗效果及预后相关因素。 设计：病例系列报告。 方法：纳入2007年2月1日至2020年1月30日首都医科大学附属北京儿童医院血液肿瘤中心确诊NB且经荧光原位杂交法确定伴有MYCN扩增的患儿,分析患儿瘤灶部位、大小、转移部位、肿瘤标记物、病理亚型、治疗情况及影响预后的相关因素。 主要结局指标：3年生存影响因素。 结果：纳入133例MYCN扩增的NB患儿,占同期收治总NB患儿的12.0%。男82例,女51例,中位发病年龄（35.7±9.8）个月;原发瘤灶位于腹膜后及肾上腺区129例（97.0%）,位于后纵隔区域4例（3.0%）;骨髓转移81例（60.9%）,骨骼转移80例（60.2%）,中枢转移24例（18.1%）;99例（74.4%）血清LDH≥1 500 U·L-1,126例（94.7%）神经元特异性烯醇化酶≥100 ng·mL-1;原发瘤灶最大直径≥10 cm者89例（66.9%）。3年OS和EFS分别为（19.7±3.5）%和（19.0±3.6）%。78例进展复发,在诱导、巩固、维持及停药后进展复发分别为8、20、46和4例,进展复发的部位以原发瘤灶、骨髓、中枢神经系统及骨骼最常见,中位首次进展时间为11.3月。伴有骨髓、骨转移、合并1p36缺失、年龄＜18月及未行自体外周血造血干细胞移植患儿预后不良。 结论：伴有MYCN扩增的NB患儿原发瘤灶以腹膜后肾上腺区为主,早期远处转移率高,50%以上患儿在维持治疗期间肿瘤进展,3年OS仅为19.7%。伴有MYCN扩增的NB患儿迫切需要靶向治疗等新的治疗手段,以提高疗效,改善预后。     

急性淋巴细胞白血病儿童染色体核型分析

目的 研究儿童急性淋巴细胞白血病(ALL)染色体变化的意义.方法 ALL患儿67例均于治疗前抽取骨髓标本1～2 mL,进行染色体核型检查,经短期培养法,收获有丝分裂期细胞,常规制片,应用G带技术进行染色体显带,分析20～30个中期细胞,根据人类染色体国际命名法描述核型.结果 1.初诊.ALL患儿67例中,克隆性核型异常37例,其中结构异常核型18例,数目异常核型16例,同时有数目和结构异常核型3例.2.t(9;22)易位的发生率为4%,且有1例t(9;22)易位中伴附加异常患儿死亡,说明t(9;22)易位核型也是小儿ALL预后不良的标志.3.t(12;21)易位是儿童ALL最常见的染色体异常,其预后良好,本组3例全部缓解.4.超二倍体和多倍体核型是预后良好的标志,而具有其他数目和结构异常核型的白血病,则预后不良.5.染色体核型正常组3例未能缓解,可能与染色体核型中微小片段改变而肉眼无法分析、临床治疗方案和病例的选择有关.结论 染色体核型分析对小儿ALL的指导治疗及预后判断具有重要作用,高二倍体核型和t(12;21)易位的ALL预后良好;而其他数目异常,t(9;22)易位和结构异常核型的ALL预后不良.     

1750例遗传咨询儿童细胞遗传学研究

目的探讨遗传咨询儿童染色体核型情况,研究染色体异常与疾病的关系。方法对1 750名遗传咨询儿童进行外周血染色体核型分析。用多重连接探针扩增技术(MLPA)检测染色体的亚端粒,确定小标记染色体(SMCs)的来源。结果共检出异常核型242例,异常率13.8%。常染色体数目异常181例,占异常核型的74.8%;常染色体结构异常28例,占11.6%;性染色体异常22例,占9.1%;染色体多态性11例,占4.5%。发现1例45,XX,psu dic(11;9)(p15;p24)核型,该核型为世界首次报道。结论染色体异常是导致儿童生长发育迟缓、智力低下和性分化异常等疾病的重要原因之一,常规染色体检查,可为临床诊断和治疗提供科学依据。     

骨髓转移的高危神经母细胞瘤治疗后骨髓缓解速度与预后关系

目的探讨伴骨髓转移的高危神经母细胞瘤(NB)患者治疗后骨髓缓解速度对预后的影响。方法收集中山大学肿瘤防治中心从2000年1月至2014年12月收治的初诊时已有骨髓转移的Ⅳ期高危NB患者的临床资料。将≤2个疗程化疗后骨髓获得完全缓解(CR)定义为快速骨髓缓解组,2个程化疗后骨髓获得CR定义为缓慢骨髓缓解组。并对综合治疗后获得CR或非常好的部分缓解(VGPR)的73例患者的预后进行单因素和多因素分析。结果纳入分析的73例患者,中位年龄4.0(1.6~9.8)岁,男52例、女2l例。快速骨髓缓解组19例,缓慢骨髓缓解组54例。全组4年无事件生存率(EFS)和总生存率(OS)分别为(15.6±4.9)%和(28.9±6.4)%。快速骨髓缓解组与缓慢骨髓缓解组4年EFS分别为(25.9±12.3)%和(12.4±5.0)%(P=0.033),4年0S分别为(51.6±15.2)%和(22.6±6.6)%(P=0.057)。单因素分析结果显示,骨髓缓慢缓解是影响骨髓转移的高危NB患儿EFS的不良因素(P0.05);无维持药物治疗、N-myc基因扩增是影响0S的不良因素(P0.05)。多因素分析结果示,N-MYC扩增、骨髓缓慢缓解为患者0S的独立不良预后因素(P0.05);仅骨髓缓慢缓解是EFS的独立不良预后因素(P0.05)。年龄≤2岁NB患者骨髓快速缓解的比例高于年龄2岁患者(x~2=5.608,spearman相关系数=0.277,P=0.018)。结论本研究显示骨髓转移的高危NB患者治疗后骨髓快速缓解者预后好于缓慢骨髓缓解者,有可能作为骨髓转移的高危NB患者的预后观察指标之一。     

急性淋巴细胞白血病患儿染色体改变及预后分析

目的应用染色体核型分析技术,探讨染色体核型异常对儿童急性淋巴细胞白血病(ALL)患儿预后判断的意义。方法回顾性分析2007年-2014年收治的初诊且伴染色体异常ALL患儿共65例的临床资料。结果 (1) 65例异常核型中单纯数目异常者21例(32%),单纯结构异常者14例(22%),数目及结构同时异常者30例(46%);(2)染色体结构异常者中,t(12;21)2例,t(9;22)6例,t(1;19)3例,t(4;11)2例。染色体数量异常者中,超二倍体核型最多,有29例(57%);(3)至随访截止时间,本组病例中生存49例,死亡11例,失访5例,复发9例。超二倍体和t(12;21)预后好,亚二倍体、t(1;19)和t(4;11)预后差;(4)本组患儿融合基因阳性22例,包括BCR/ABL6例,MLL2例,TEL/AML1 8例,E2A/PBX1 6例。与染色体结果比对,8例TEL/AML1仅测得2例t(12;21),6例E2A/PBX1中测得2例t(1;19),另外一例t(1;19)对应的融合基因阴性。结论 (1)本组ALL患儿染色体改变以数目及结构同时异常为主,数目异常中以超二倍体核型最为常见。(2)染色体核型与ALL预后有密切联系。(3)t(12;21)及t(1;19)染色体检测阳性率低于融合基因阳性率。     

Distal chromosome 17 gains in neuroblastomas detected by comparative genomic hybridization (CGH) are associated with a poor clinical outcome

PROCEDURE: To establish the significance of chromosome 17 aberrations in the biology of neuroblastomas, the fresh-frozen material of 53 primary neuroblastomas (average patient age: 20.8 months; stage 1 or 2: n = 10; stage 3: n = 10; stage 4: n = 10; stage 4s: n = 23) was studied by means of comparative genomic hybridization (CGH). Follow-up data were available for 52 of 53 cases studied (average follow-up period: 26.4 months). Except for one, all cases had previously been analyzed for MYCN status (semiquantitative Southern blot analysis). Studies of LOH 1p36 (VNTR-PCR) had been performed on 28 of 53 cases. RESULTS: Chromosome 17 gains were detected in 46 of 53 (86.8%) cases. Whole chromosome gains were mostly restricted to localized tumors (stage 1 or 2: 9 of 10 cases; stage 4s:19 of 23; stage 3: 2 of 10; stage 4:0 of 10 cases), whereas distal 17 gains were significantly associated with clinically advanced tumor stages and patients aged over 1 year at diagnosis. Univariate analyses revealed a statistically significant correlation of distal 17q gains with overall survival (P< 0.01, MYCN amplification: P< 0.01; 1p deletion: P< 0.01) and an elevated recurrency rate (17q: P= 0.02, MYCN amplification: P = 0.05; 1p deletion P= 0.3). There was a strong coincidence of distal 17q gains and 1p deletion or MYCN amplification (P < 0.01). CONCLUSION: Our data indicate that distal chromosome 17q gains are of major prognostic relevance for neuroblastoma patients. However, studies on a larger series of tumors have to be performed to assess whether or not these alterations are independent prognostic markers of a poor clinical outcome.     

Comprehensive analysis of chromosome 1p deletions in neuroblastoma

BACKGROUND: Chromosome 1p deletions are common in advanced neuroblastomas, but the biological and clinical implications of this clonal rearrangement remain controversial. Previous studies of chromosome 1p loss of heterozygosity (LOH) have been limited by analyses of relatively small number of tumors derived from heterogeneously assessed and treated patient populations. Therefore, a strictly representative cohort of 288 Children's Cancer Group neuroblastoma patients treated on the most recent phase III therapeutic trials was identified. PROCEDURE: Primary tumors from these patients were analyzed for LOH at precisely mapped and highly informative 1p polymorphic loci located from 1p32 to 1p36.3 by multiplex PCR. RESULTS: Ninety-three primary tumor specimens (32%) had LOH at multiple 1p36 marker loci. All 1p deletions overlapped the previously determined smallest region of overlap (SRO). One tumor had a small terminal deletion completely within 1p36.3, allowing for further refinement of the 1p36 SRO. We found no evidence to support an additional, nonoverlapping region of LOH within 1p32-36. We confirmed the strong correlation of 1p36 LOH with MYCN amplification (P < 0.001), advanced disease stage (P < 0.001), and decreased both 3-year event-free survival and overall survival probabilities (P< 0.001). When stratified for MYCN amplification status or entered into a multivariate analysis, 1p36 LOH remained predictive for decreased event-free survival, but not overall survival probability. CONCLUSIONS: These data support the hypothesis that inactivation of a tumor suppressor gene within 1p36.3 is associated with an increased risk for disease relapse.     

Bone marrow karyotypes of children with nonlymphocytic leukemia.

Bone marrow (BM) karyotypes from 16 consecutive children presenting with nonlymphocytic leukemia were established with the use of banding techniques, before therapy. The two patients with chronic myeloid leukemia (CML) showed the Philadelphia (Ph1) translocation (9q+;22q-). Five of the 14 patients with an acute nonlymphocytic leukemia (ANLL) presented no acquired cytogenetic abnormalities, but one of these five showed a high level of hypodiploidy. One patient with AML evidenced a variant of the Ph1 chromosome originated as a translocation (12p+;22q-). Nonrandom abnormalities (-7; 7q-; +8; t(8;21); -21) were found in six patients, isolated or in association with otheraberrations. Among the random abnormalities, apparently balanced translocations and chromosomal deletions were observed. In ANLL, no correlation could be found between morphologic diagnosis and cytogenetic findings. On the other hand, the presence of BM cells with a normal karyotype at diagnosis was associated with an improved remission rate and survival time. Followup studies were performed in four ANLL patients with an abnormal cell clone at diagnosis. Three of them achieved hematologic remission; their BM karyotype was found to be normal at that stage. In the 4th patient, generalization of the abnormal karyotype in BM cells was seen in the terminal phase of the disease.     

儿童初治肝母细胞瘤83例临床特征及预后分析

目的探讨肝母细胞瘤(HB)患儿的临床特征、生存情况及预后危险因素。方法回顾性分析2012年1月至2019年10月郑州大学第一附属医院儿童医院血液肿瘤科收治的83例初治HB患儿的临床资料, 记录患儿的性别、年龄、首发临床表现、治疗前病变范围(PRETEXT)分期、病理类型、病初甲胎蛋白(AFP)、治疗方法及治疗结果。2018年之前确诊的患儿采用"武汉方案"治疗, 2018年之后确诊的患儿采用"儿童肝母细胞瘤多学科诊疗专家共识(CCCG-HB-2016)"方案治疗。Kaplan-Meier生存分析法计算生存率, 单因素分析采用Log-Rank检验, 多因素预后分析采用Cox回归模型。结果 83例患儿中男51例、女32例;发病年龄25.2(9.0, 34.0)月龄, <3岁64例(77%)。最常见的首发临床表现为腹部包块(45例, 54%)。PRETEXT Ⅰ期8例, Ⅱ期43例, Ⅲ期20例, Ⅳ期12例。随访时间40(17, 63)个月, 全组HB患儿1年总体生存率(OS)和无事件生存率(EFS)分别为(84±4)%和(79±5)%, 5年OS和EFS分别为(78±5)%和(76±...     

Genomic profile in high risk neuroblastoma by comparative genomic hybridization

Different subtypes of neuroblastoma (NB) carry associated genetic aberrations that predict their clinical course. Whole chromosome gains are usually associated with early clinical stages and good prognosis, while 1p deletion, 17q gain and MYCN amplification (MNA) are related to advanced stages and poor prognosis. High-risk neuroblastomas (NB-HR) include NB in children aged more than 1 year old, either stage 4 or any stages showing MNA except stage 1. The prognosis of NB-HR patients remains poor, despite aggressive therapy. Only MNA confers poor prognosis. Between January 2000 and February 2005, tumoral specimens from 60 patients with NB-HR were sent to the Spanish Reference Center for NB biological studies. In all cases, MYCN together with 1p36 status was analyzed by fluorescence in situ hybridization (FISH). Comparative genomic hybridization (CGH) was performed in 24 cases. Using FISH we detected 31 MNA cases including 29 with 1p36 deletion; there were 21 cases without MYCN amplification (MNNA) but 7 of these had 1p36 deletion; 8 cases showed MYCN gain (MNG) but 6 of these had 1p36 deletion. CGH showed other chromosomal alterations. Of 11 MNA cases, none had 11q loss and all of them showed 17q gain or 17 disomy. Of the 7 MNNA cases, there were 4 with 11q loss including 2 with 3p loss and all presented 17q gain or 17 disomy. The 6 MNG cases included 4 cases with 11q loss and 5 cases with 17q gain or 17 disomy. Genomic profiling by CGH in NB-HR confirms the interaction among genetic alterations, the prognostic significance of which should be evaluated to establish new treatment criteria.     

17q gain in neuroblastoma predicts adverse clinical outcome. U.K. Cancer Cytogenetics Group and the U.K. Children's Cancer Study Group

BACKGROUND: It is now recognized that gain of chromosome 17 material is the most frequent genetic abnormality of neuroblastoma cells. Several studies have linked 17q gain with known adverse prognostic factors: patient age >1 year, advanced stage disease, deletion of chromosome arm 1 p, and amplification of the MYCN oncogene. We sought to further investigate the clinical and prognostic associations of chromosome 17 status in relation to other well-established predictive factors. PROCEDURE: In a collaborative study by UK cytogenetics centres, we compiled a series of 104 neuroblastoma tumours for which the status of chromosome 17 was confidently defined by cytogenetics, metaphase or interphase FISH, or CGH analysis. The results were correlated with data on 1p and MYCN, and with centrally collated clinical and survival information. RESULTS: Gain of 17q (i.e., unbalanced gain of segment 17q21-qter) was found in 66.3% of tumours, while 33.7% showed a '17q normal' status (i.e., no gain at all, or gain of whole chromosome 17 relative to ploidy). Gain of 17q was strongly associated with advanced stage disease, patient age >1 year, 1p deletion, and MYCN amplification (all P< 0.01). In univariate analysis, 17q gain was a significant predictor of adverse outcome (projected 5 year relapse-free survival 15.6% compared to 75.2% in cases lacking this feature in tumour cells; (P < 0.0001). In multivariate analysis, 17q gain was more strongly associated with adverse outcome than was either stage (Stage 4 vs other combined) or 1p status. CONCLUSION: We conclude that gain of chromosome segment 17q21-qter is of great biological and clinical importance in neuroblastoma, and that its detection at diagnosis should be a priority.     

Cytogenetic Analysis of Childhood Endodermal Sinus Tumors: A Pediatric Oncology Group Study

Most adult germ cell tumors have a consistent cytogenetic abnormality, i(12p), and are aneuploid. Many pediatric germ cell tumors are biologically distinct from their adult counterparts, particularly endodermal sinus tumors (ESTs) of young children. We report cytogenetic and ploidy analysis of nine ESTs involving children under 3 years of age (four extragonadal and five testicular). Structural abnormalities were present in seven tumors and were identifiable in six: 5/6 had a structural abnormality of chromosome 1, usually terminal deletion of 1p; 5/6 showed 6q deletion; 3/6 had structural abnormalities of 3p; 2/6 showed abnormalities of chromosome 2. None showed an i(12p) or abnormality of chromosome 12. Ploidy analysis of the tumors correlated with the cytogenetic analysis; in particular, the tumor that was cytogenetically normal showed no aneuploid peaks. To determine if a marker chromosome was derived from chromosome 12 or if karyotypically normal cases included nondividing tumor cells, interphase fluorescence in situ hybridization using an alpha satellite probe for chromosome 12 was performed. These studies showed no evidence of an i(12p). We conclude that ESTs in young children show cytogenetic differences from their adult counterparts and that loci on 1p, 6q, and 3q need to be further studied.     

肝肿瘤切除术治疗POST-TEXTⅢ期和Ⅳ期肝母细胞瘤的中长期疗效分析

目的探讨肝肿瘤切除术治疗POST-TEXT(post-treatment extent of disease)Ⅲ期和Ⅳ期肝母细胞瘤的中长期治疗效果。方法回顾性分析2009年1月至2019年6月复旦大学附属儿科医院肿瘤外科收治的POST-TEXTⅢ期和Ⅳ期肝母细胞瘤患儿的临床资料(包括PRETEXT分期、甲胎蛋白、CT或MRI影像学资料、肿瘤切除术式及预后结果)。采用SPSS18.0统计软件包中的Kaplan-Meier法进行生存分析。结果本研究共纳入POST-TEXTⅢ期和Ⅳ期肝母细胞瘤患儿37例,其中男25例,女12例,发病年龄2~91个月,平均发病年龄(23.92±22.45)个月。POST-TEXTⅢ期和Ⅳ期分别为34例和3例,其中1例PRETEXTⅡ期病例治疗过程中升级为POST-TEXTⅣ期,3例PRETEXTⅣ期病例治疗过程中降级为POST-TEXTⅢ期。新辅助化疗2个、4个和6个疗程内手术人数分别为8例(21.6%)、22例(59.4%)和7例(18.9%)。除2例被建议行肝移植手术后放弃治疗外,其余35例均进行肝肿瘤切除术,其中肝三叶切除术7例,扩大半肝切除术8例,不规则肝切除术4例,肝中叶切除术12例,ALPPS(associating liver partition and portal vein ligation for staged hepatectomy)术4例。平均手术时间(262.29±107.16)min,术中平均出血量(236.86±212.41)m L。采用Glisson蒂横断技术22例,平均出血量(147.73±137.46)m L,胆漏发生率27.3%,与未采用该技术的病例比较,出血量明显减少[(147.73±137.46)m L vs.(387.69±235.69)m L,P=0.001],胆漏发生率相似(27.3%vs.23.1%,P=0.784)。术中切缘>1 cm者7例(20.0%),切缘0.5~1 cm者15例(42.9%),切缘<0.5 cm者7例(18.9%),紧贴肿瘤边缘切除者6例(16.2%)。随访时间4~124个月,术后肿瘤复发7例,平均复发时间(6±3.96)个月。肿瘤复发率与手术方式及术中切缘距离均无相关性(P>0.05)。5年总体生存率为72.3%,5年无瘤生存率为67.4%。根据切缘距离分类,切缘>1 cm、切缘0.5~1 cm、切缘<0.5 cm及紧贴肿瘤者5年总体生存率分别为85.7%、78.0%、83.3%和53.3%,各组间差异均无统计学意义(P=0.701)。结论对于POST-TEXTⅢ期和Ⅳ期的肝母细胞瘤,根据肿瘤累及的不同部位选择相应的术式,可以取得较好的治疗效果。熟练掌握Glisson鞘分离技术可以减少术中出血和胆道损伤的发生。手术中只需确保一定的切缘距离,就可以减少肿瘤复发,提高远期生存率。     

Cytogenetic abnormalities and clinical outcome in Wilms tumor: a study by the U.K. cancer cytogenetics group and the U.K. Children's Cancer Study Group

BACKGROUND: Tumor genetic features reported to correlate with adverse outcome in Wilms tumor include karyotype complexity, losses of material from the short arm of chromosome 1 and from the long arms of chromosomes 11, 16 and 22 and gain of material from the long arm of chromosome 1. This study sought to test these associations in a large series of tumors studied by cytogenetic analysis. Identification of markers associated with elevated risk of relapse and fatal outcome could allow more effective treatment stratification at presentation. PROCEDURE: Thirteen member laboratories of the U.K. Cancer Cytogenetics Group provided results from a 12-year period. Karyotype abnormalities were correlated with clinical data (age, tumor stage, and histology) and outcome data provided by the central register of the U.K. Children's Cancer Study Group. RESULTS: Of 127 abnormal karyotypes, 78 included a reputedly "poor prognosis" feature. Univariate survival analysis showed no significant adverse effect for karyotype complexity, 1p loss or 11q loss. The poor outcome of cases with 16q loss was of borderline significance, but this effect was restricted to those tumors with unbalanced translocation der(16)t(1q;16q). The association between relapse risk and gain of 1q material was not significant. Only monosomy 22 was a significant marker of poor outcome in univariate analysis (13 cases showing 50% relapse free survival at 5 years compared to 79% survival for the remaining 114 cases, P = 0.02). In multivariate analysis, significant independent predictors of poor outcome were 1q gain (Hazard Ratio 3.4), stage IV disease (HR 5.0), and monosomy 22 (HR 5.9). CONCLUSIONS: Loss of chromosome 22 identifies high risk Wilms tumors. The prognostic significance of 1q gain, 16q loss and unbalanced translocation der(16)t(1q;16q) is unresolved and warrants further investigation.