小儿恶性肿瘤介入治疗进展

常用的肿瘤介入治疗包括经导管的动脉化疗栓塞(TACE)和经导管的动脉灌注化疗(TAIC或IAC)。TACE是将化疗药与栓塞剂注入肿瘤供血动脉,适用于肝、肾肿瘤。TAIC用于其他部位的肿瘤,只注入化疗药物而不用栓塞剂,进行局部的动脉大剂量冲击化疗,而避免邻近脏器受到栓塞。介入治疗所用的化疗药物有卡铂或顺铂,多柔比星或表柔比星,5-氟尿嘧啶,长春新碱或长春地辛等。栓塞剂有碘油、明胶海绵颗粒、微球颗粒等。根据肿瘤的状况,介入治疗可间隔4周重复1～3次,直至估计手术能完整切除肿瘤。国内TACE应用最多的儿童肿瘤为肝母细胞瘤和晚期肾母细胞瘤。TAIC被用于盆腔、卵巢、阴道、膀胱、骶尾部、腹腔、大网膜、肠系膜根部、臀部、上臂等部位恶性肿瘤的治疗。介入治疗与静脉用药全身化疗的交替应用具有更好的治疗作用。     

Ⅲ、Ⅳ期肾母细胞瘤综合治疗15年经验

目的总结近15年来对Ⅲ、Ⅳ期。肾母细胞瘤患儿的多模式综合治疗经验。方法1995年5月至2010年12月浙江大学医学院附属儿童医院共对26例单侧Ⅲ、Ⅳ期肾母细胞瘤患儿采用多模式的综合治疗。诊断标准：肾门、主动脉旁淋巴结转移;弥漫性腹腔播散或术时散落;腹膜有肿瘤种植;镜检或肉眼有肿瘤残留;局部浸润至重要脏器;肿瘤远处转移。全部病例按年限和治疗方式分为两组：①术前单纯介入治疗组（TACE组）11例,为1995年至2002年收治病例,采用术前肾动脉化疗栓塞（TACE）,1周后手术切除瘤肾,术后化疗或加放疗的综合治疗;②术前介入治疗加短期全身化疗组（T＋S组）15例,为2003年至2010年收治病例,采用术前TACE加2～3周静脉化疗,然后手术切除瘤肾,术后化疗或加放疗的综合治疗。TACE采用吡柔比星40mg／m。,长春地辛3mg／m2,超液碘油5～10mL。术前短期静脉化疗采用长春地辛3mg／（m2·周）,共2次;放线菌素D10we／（kg·d）,共5次。术后化疗和放疗按照北京儿童医院肾母细胞瘤治疗方案。TACE组与T＋s组分别有3例和9例接受术后放疗。结果两组患儿术后分期为：TACE组Ⅲ期10例,Ⅳ期1例;T＋S组Ⅲ期11例,Ⅳ期4例。两组各有弥漫问变型2例。两组肿瘤完整切除率分别为63．6％（7／11）和80．0％（12／15）,P=0．407。随访至2010年12月,两组平均随访时间分别为118（102—186）个月和43．5（1～92）个月,无瘤生存率分别为72．7％和100．0％,Kaplan-Meier生存分析显示两组差异有统计学意义（P=0．040）。结论本研究表明,术前动脉栓塞化疗加短期静脉化疗,手术切除瘤肾,术后继续化疗和放疗的多模式综合治疗是对Ⅲ、Ⅳ期肾母细胞瘤患儿的合理治疗方案。     

不可切除型肝母细胞瘤的术前介入治疗临床研究

目的探讨术前介入性动脉栓塞化疗（TACE）在不可切除型肝母细胞瘤治疗中的可行性。方法分析对8例经检查诊断为不可切除型肝母细胞瘤行TACE的治疗结果。结果8例患儿TACE后均有不同程度呕吐、发热、一过性肝功能损害，1例有骨髓抑制，无心、肾功能损害。有6例复查B超检查，肿瘤体积较前均有明显缩小，缩小比例为22．5％～57．5％；5例手术完整切除，均已无瘤存活1～4年，3例复诊检查发现有肺转移或多发转移，家属放弃进一步治疗后死亡。结论TACE具有化疗药物剂量小、全身副作用少、化疗效果好的优点，可作为一种术前治疗方法应用于不可切除型肝母细胞瘤。     

婴儿肝母细胞瘤的介入治疗及延迟手术治疗

目的　评价经动脉栓塞化疗 (TACE)结合延迟手术治疗婴儿巨大肝母细胞瘤的效果。方法　 2 0 0 0年 1月～ 2 0 0 4年 1月不能手术切除的肝母细胞瘤 8例患儿 (男 6例 ,女 2例 )接受 1～ 3次栓塞化疗。年龄 2～ 12个月。每次栓塞化疗前均行数字减影血管造影 (DSA)检查 ,栓塞化疗时首先超选择进入肿瘤的供血动脉 ,经该动脉先灌注化疗药物和超液化碘油的混悬乳液 ,再使用弹簧圈栓塞该肿瘤血管。结果　每次TACE均未遇到任何大技术问题和明显化疗毒性反应。 6例TACE结合手术患儿及经 3次TACE及静脉化疗患儿均无瘤存活至今。另 1例 1个月后死于肺炎。结论　TACE是治疗婴儿肝母细胞瘤有效、安全的方法     

晚期肾母细胞瘤的术前治疗

目的　探讨晚期肾母细胞瘤术前治疗的必要性 ,并分析术前全身化疗和肾动脉化疗栓塞合并全身化疗的治疗效果。方法　 30例Ⅲ、Ⅳ期肾母细胞瘤分为 2组 :①未术前治疗组 11例 ;②术前治疗组 19例 (又分为全身化疗亚组 6例和肾动脉化疗栓塞合并全身化疗亚组 13例 )。结果　未术前治疗组手术死亡率 18.2 % (2 /11) ,肿瘤完整切除率 9.1% (1/11) ,2年无瘤生存率 9.1% (1/11)。术前治疗组手术死亡率 0 % (0 /19) ,肿瘤完整切除率 6 3.2 % (12 /19) ,2年无瘤生存率 73.7% (14 /19)。肿瘤完整切除率比较和 2年无瘤生存率比较差异均有高度显著性意义 (<0 .0 1)。术前治疗组中 ,肾动脉化疗栓塞合并全身化疗亚组完整切除率和 2年无瘤生存率均高于全身化疗亚组。结论　术前治疗可明显提高Ⅲ、Ⅳ期肾母细胞瘤的完整切除率和 2年无瘤生存率。术前肾动脉化疗栓塞与全身用药化疗并用疗效更好。     

动脉化疗栓塞术对小儿肾母细胞瘤细胞凋亡和增殖的影响

目的探讨动脉化疗栓塞术(TACE)对肾母细胞瘤(WT)细胞凋亡指数(AI)和细胞增殖指数(PI)的影响,并评价其在临床治疗中的地位。方法将24例肾母细胞瘤患儿按临床分期、病理分型进行配对设计研究,设动脉化疗栓塞组12例,全身化疗组12例,采用TUNEL法和免疫组织化学超敏二步法测定标本的细胞凋亡指数和细胞增殖指数。结果动脉化疗栓塞组AI高于全身化疗组(P<0.05),PI低于全身化疗组(P<0.05),AI与PI成负相关(P<0.05),动脉化疗栓塞组术后瘤体缩小,坏死程度高于全身化疗组(P<0.05),而骨髓抑制少(P<0.05)。结论与全身化疗组相对比,术前采用动脉化疗栓塞法能更有效地诱导肿瘤细胞凋亡,抑制肿瘤细胞增殖,促使肿瘤缩小、坏死,有利于手术根治,取得更好的疗效,提高生存率。     

经导管动脉化疗栓塞在肝母细胞瘤综合治疗中的应用评价及文献回顾

目的：探讨经导管动脉化疗栓塞术（TACE ）在肝母细胞瘤综合治疗中的作用及疗效。方法回顾性总结2005年-2013年收治的10例经TACE 治疗的肝母细胞瘤患儿的临床资料。随访治疗后患儿的全身情况、血AFP值及瘤体体积大小的变化及生存情况。结果患儿10例,男女比例4∶1,发病中位年龄9.5个月（1个月～10岁）,10例患儿首诊后均予以1～4次TACE 治疗,其中6例TACE＋手术＋化疗,1例TACE＋化疗,3例在TACE 治疗后放弃继续治疗。介入治疗后肿瘤体积较前均有明显缩减（26.2％～10.00％,平均70.0％）,血清AFP值下降明显（28.5％～99.7％,平均83.6％）。所有患儿在接受TACE 治疗后均出现不同程度的发热、呕吐、一过性肝功能损害（Ⅰ度3例,Ⅱ度2例,Ⅲ度1例）、轻度骨髓抑制、贫血等不适,未见明显心脏毒性及肾毒性损害。随访时间2～114个月,平均随访时间为36.1个月,1年存活率100％（7／7）,2年存活率86％（6／7）,3年存活率71％（5／7）。6例患儿在接受TACE治疗后成功行手术切除,术后均接受全身化疗,1例仅经过4次TACE治疗及化疗后肿瘤消失,未行手术治疗,均无瘤存活至今。3例放弃治疗患儿分别于2～8个月后死亡。结论 TACE治疗可作为肝母细胞瘤术前重要的辅助治疗方式,能够使肿瘤体积明显缩小,血供减少,促进肿瘤包膜增厚,为尽可能完整切除创造了条件,能够改善肝母细胞瘤患儿的生活质量,提高长期存活率。     

经导管动脉化疗栓塞联合手术治疗儿童肝母细胞瘤

目的 探讨对不能切除的小儿肝母细胞瘤实行动脉化疗栓塞术(TACE)治疗的临床可行性、疗效及作用.方法 8例常规不能切除的肝母细胞瘤经TACE治疗20次,再行Ⅱ期外科手术切除,比较分析治疗前后临床症状、体征和血AFP的变化、术中情况及随访远期疗效.结果 TACE术后4～6周复查,和术前相比.肿瘤体积缩小67.68%～95.91%,平均缩小87.91%(t=3.754,P=0.007),血AFP下降94.46%～99.97%,平均98.45%(t=2.931,P=0.022),无明显的化疗毒性反应,所有患儿手术完整切除肿瘤,术后病理显示肿瘤明显坏死.随访8～24个月,所有患儿均获无瘤生存.结论 TACE治疗肝母细胞瘤安全有效,无严重并发症,能使部分不能Ⅰ期手术的患儿重新获得手术机会,并对减少术中肿瘤细胞的扩散和术中出血、改善预后有较大作用,可作为无远处转移肝母细胞瘤的术前辅助治疗.     

肾母细胞瘤手术前介入治疗的疗效评价

目的　评价肾母细胞瘤术前介入性肾动脉栓塞化疗的可行性及疗效。方法　观察分析17例肾母细胞瘤患儿TACE前后临床症状的变化及反应 ,同时与 2 2例单纯手术者比较术中情况和远期疗效。观察指标有 ,肿瘤体积 ,术中情况 ,肿瘤切除。结果　TACE后肿瘤平均缩小 4 1.7%。,总有效率 76 .5 % (13/17) ;术前介入组肿瘤完全切除率、术中平均出血量、肿瘤坏死区域面积分别为 :10 0 %、(14 2 .2± 73.2 )ml、6 0 .0 % ,单纯手术组分别为 6 3.6 %、(2 5 8.2± 2 14 .4 )ml、15 .0 % ;术前介入组 15例 (15 /17)获随访 ,2年无瘤生存率 73.3% (11/15 ) ;单纯手术组 14例 (14 /2 2 )获随访 ,2年无瘤生存率 4 2 .9% (6 /14 )。结论　肾母细胞瘤TACE ,能有效杀死肿瘤细胞 ,控制肿瘤生长 ,提高肿瘤完整切除率 ,改善预后 ,无严重并发症 ,是有效的术前治疗方法     

介入治疗在小儿腹部恶性肿瘤的应用

目的 对巨大腹部肿瘤采用介入治疗,为肿瘤完整切除创造有利条件。方法 对１２例腹部恶性肿瘤患儿进行介入治疗,其中男７例,女５例。年龄２个月￣７岁。肝母细胞瘤６例,神经母细胞瘤３例,肾母细胞瘤２例肾上腺皮质癌１例。采用Ｓｅｌｄｉｎｇｅｒ’ｓ技术进行动脉插管造影,确定肿瘤主要供血动脉,进行肿瘤供血动脉超选择性插管,局部注入化疗药物,然后用碘油、明胶海绵或白芨微球栓塞肿瘤的供血动脉。结果 １２例中７例手术     

Chemotherapy-Induced Histologic Changes in Wilms' Tumors

The nephrectomy specimens of 21 patients with Wilms' tumor who received preoperative chemotherapy consisting of vincristine and actinomycin D, alone or in combination, were studied pathologically; 1 patient also received radiation therapy. Pathological material from 20 randomly selected patients with Wilms' tumor who did not receive preoperative chemotherapy was reviewed and used as a control. Twenty tumors were of favorable histology, and one was unfavorable; all control tumors were of favorable histology. The histological changes were diffuse. The most marked changes occurred in the undifferentiated stroma of 18 tumors: the stroma was edematous; had a fibrovascular background, granulation tissue, and histiocytes; and lacked atypical cells. The blastematous nodules were reduced in size and necrotic or undergoing necrosis in 5 cases. Differentiated elements, including glomeruloid, tubular, and rhabdomyoblastic components, were unaffected. Vascular changes, consisting of fibrinoid necrosis, thrombosis, and acute inflammation were prominent in 15 instances. Two tumors of favorable histology, including one that was a rhabdomyomatous Wilms' tumor, and the tumor of unfavorable histology were unchanged by the therapy. In contrast, the histological changes present in only 4 of the control group, while similar, were rather minimal and focal. This evaluation helps to define the susceptibility of the different elements in Wilms' tumor to chemotherapy.     

Chemotherapy-induced histologic changes in Wilms' tumors

The nephrectomy specimens of 21 patients with Wilms' tumor who received preoperative chemotherapy consisting of vincristine and actinomycin D, alone or in combination, were studied pathologically; 1 patient also received radiation therapy. Pathological material from 20 randomly selected patients with Wilms' tumor who did not receive preoperative chemotherapy was reviewed and used as a control. Twenty tumors were of favorable histology, and one was unfavorable; all control tumors were of favorable histology. The histological changes were diffuse. The most marked changes occurred in the undifferentiated stroma of 18 tumors: the stroma was edematous; had a fibrovascular background, granulation tissue, and histiocytes; and lacked atypical cells. The blastematous nodules were reduced in size and necrotic or undergoing necrosis in 5 cases. Differentiated elements, including glomeruloid, tubular, and rhabdomyoblastic components, were unaffected. Vascular changes, consisting of fibrinoid necrosis, thrombosis, and acute inflammation were prominent in 15 instances. Two tumors of favorable histology, including one that was a rhabdomyomatous Wilms' tumor, and the tumor of unfavorable histology were unchanged by the therapy. In contrast, the histological changes present in only 4 of the control group, while similar, were rather minimal and focal. This evaluation helps to define the susceptibility of the different elements in Wilms' tumor to chemotherapy.     

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。     

胎儿横纹肌瘤型肾母细胞瘤

目的 探讨胎儿横纹肌瘤型肾母细胞瘤（ＦＲＮ）特点和恰当的治疗方法。方法 从１９５５～１９９６年３６９例肾母细胞瘤中检出ＦＲＮ１０例。回顾性分析其临床表现、病理组织学特点和预后。结果 １０例ＦＲＮ均因腹部肿大或腹部肿物入院。经术前放、化疗肿瘤不缩小。６例单侧病变做瘤肾切除,５例获随访均长期存活。４例双侧病变中１例做双侧单纯肿瘤切除,３例做一侧瘤肾切除,对侧肾部分切除或单纯肿瘤切除,随访存活２年。结论     

化疗对肾母细胞瘤细胞凋亡及坏死的影响

目的 了解化疗对肾母细胞瘤细胞凋亡和坏死的影响。方法 对４４例肾母细胞瘤进行随机分组，Ａ组２６例，给予ＶＡＣ术前化疗，其中８例尚加用了介入化疗，Ｂ组１８例，Ｉ期手术治疗。用ＴＵＮＥＬ技术和常规病理检查观察了全部标本的凋亡和坏死情况，并分组进行了比较。结果 术前化疗后Ａ组瘤体凋亡指数（ＡＩ）较Ｂ组明显增加；Ａ组中化疗时间超过两周的病例ＡＩ较不足两周病例也有明显上升；但死亡和获两年以上生存病例，介入和     

Renal cell carcinoma in children

Renal cell carcinoma is a rare tumor in childhood, however, rare tumors must be kept in mind if tumor therapy protocols like the SIOP-9 or SIOP 93-01 Wilms' tumor trial include preoperative chemotherapy based on clinical and radiologic findings without further histologic tumor confirmation. We present a 12-year-old boy initially believed to have a stage IV Wilms' tumor with pulmonary metastasis. Following chemotherapy with doxorubicin, vincristine, and actinomycin D, subsequent tumor nephrectomy revealed a highly differentiated renal cell carcinoma (pT₂pN₀). Wedge resection of the lung showed no evidence of a pulmonary metastasis (M₀). The benefit of preoperative chemotherapy with regard to downstaging of the tumor must be considered carefully, taking into account the risk of incorrect tumor diagnosis.     

Controversies in the management of Wilms' tumor

Wilms' tumor is the most common malignant renal tumor of childhood; it represents 5% to 6% of childhood cancers in the United States. The survival rate of children with Wilms' tumor has improved dramatically, partly due to large multicenter studies conducted by the National Wilms' Tumor Study Group and the International Society of Pediatric Oncology. To ensure optimal patient outcome, the surgical management of these patients must be appropriate. Controversial issues in the management of Wilms' tumor include the value of preoperative chemotherapy; whether pre-resection biopsy is indicated and if so, how this is best performed; indications for partial nephrectomy; the treatment of low-risk patients with surgery only; and the reliability of preoperative imaging to assess the contralateral kidney.     

Bilateral Wilms' tumor--surgical aspects.

Four to eight percent of all Wilms' tumors are bilateral. Achieving curative resection of such tumors by partial nephrectomy or tumor enucleation while maintaining sufficient renal function represents a surgical challenge. Effective preoperative chemotherapy facilitates this aim considerably. Seven patients who were diagnosed to have bilateral synchronous Wilms' tumors between 1990 and 1994 are being reviewed. At the time of initial diagnosis, their mean age was 24.4 months, range 7 to 45 months. In 4 cases, pre-operative imaging did not reveal the full extent of the lesions, and in one of these, involvement of the second kidney was only detected by surgical exploration. Five of the children received at least 4 weeks of neo-adjuvant chemotherapy without primary biopsy, followed by bilateral tumor resection. One child had to be operated on as an emergency without any preliminary treatment, and in one, chemotherapy was interrupted after 3 weeks because of veno-occlusive disease. After a follow-up period of 66 months on the average (range 50 to 81 months), five of the patients are free of recurrence and clinically well--one with a kidney graft. The remaining two patients have died. Discussion is focussed on different management strategies of this rather rare pathology considering SIOP und NWTS protocols.     

Radiological diagnostics and radiotherapy in Wilms' tumor (author's transl)

The possibilities of diagnosing Wilms' tumor correctly have been greatly extended by the introduction of computerised tomography and ultrasonic examination. In view of the fact that Wilms' tumor is subjected to combined treatment involving chemotherapy, surgery and radiotherapy, it appears justified to reduce the dose to 20--30 Gy, depending upon the age of the child and the extension of the tumor. It is believed that preoperative radiotherapy will yield better surgical possibilities in large tumours. Radiotherapy can be omitted in infants in the stages I and II as well as in children in stage I.     

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.