肾母细胞瘤动脉栓塞化疗及机理的研究
|
摘要
肾母细胞瘤为儿童最常见的恶性实体瘤之一，占小儿肾脏肿瘤第一位，3岁以前是发病的高峰期。该肿瘤早期症状不明显，但发展迅速，就诊时常肿瘤已巨大，难以完整切除，预后较差。随着以手术、化疗、放疗等综合治疗的应用，使肾母细胞瘤的总体治愈率已明显提高。其中，术前化疗在中晚期肾母细胞瘤治疗中的作用已得到公认。术前介入治疗(动脉栓塞化疗Transcatherter arterial chemo-embolization，TACE)在肝肿瘤治疗中的应用大大提高了肿瘤的完整切除率和生存率。但在肾母细胞瘤治疗中的应用尚少。肾动脉是肾母细胞瘤的主要供血血管，血流丰富，适于进行经动脉的化疗栓塞，而且化疗栓塞前的肾动脉造影还有助于与肾外肿瘤的鉴别诊断。因此本院在国内首先将TACE应用于肾母细胞瘤的治疗，在数字减影X线下(DSA)将化疗药与栓塞剂(碘化油)混合后经导管直接注入瘤肾供养血管，栓塞肿瘤血管。碘油长期滞留在瘤肾内，肿瘤血流明显减少。化疗药长时间局限在瘤肾内缓慢释放，剂量小而局部浓度高，能更好发挥
2004年浙江大学硕士论文
肿瘤细胞杀灭作用而全身毒副作用较小。
增殖细胞核抗原(PCNA)存在于细胞核内。静止期细胞内含量极少，增殖细
胞或转化细胞中表达量高，在G!晚期及S期表达量最高，M期末降解消失，是研
究细胞增殖活性的重要指标。PCNA的表达在肿瘤的发生发展中具有重要作用。
肿瘤的生长、肿瘤的转移及转移部位的生长均有赖于肿瘤组织新生血管的生
成，目前己知血管内皮生长因子(VEGF)是参与血管生成的最重要的一种生长因
子。它特异作用于血管内皮细胞，促进内皮细胞的有丝分裂和趋化作用，还增加
血管通透性，使管内的纤维蛋白原等外渗，不仅为内皮细胞迁移和新生毛细血管
网的建立提供必要的基质，也为肿瘤的生长提供良好的基质。
本研究旨在对肾母细胞瘤术前动脉栓塞化疗的方法、疗效、患儿的耐受程度、
毒副反应和作用机理包括肿瘤细胞退变情况、肿瘤细胞的增殖细胞核抗原(PCNA)
和血管内皮生长因子(VEGF)表达的改变等进行研究。进一步提高肾母细胞瘤，
尤其是晚期肾母细胞瘤的疗效。
材料与方法
.病例与分组:
肾母细胞瘤41例。住院后经腹部B超、CT和/或静脉肾盂造影初步诊断为
肾母细胞瘤。分为两组:①TACE组:23例，行术前动脉栓塞化疗，2周左右再行
肿瘤切除术;②对照组:18例，未应用术前动脉栓塞化疗而直接手术切除肿瘤。
2004年浙江大学硕士论文
组织分型按照国际小)匕肿瘤学会(SIOP)和美国Wilms，瘤研究组(NWTS一3)的
分型法分为“预后好的组织结构(FH)”和“预后差的组织结构(UH)”。分期根
据NWTS一3的标准。术前临床分期:TACE组23例包括I期6例、n期O例、m
期9例、W期1例、因肿瘤巨大难以分期7例，其中15例手术前进行细针肿瘤穿
刺活检，13例为良好组织学类型(FH)，1例不良组织学类型(UH)，1例为小片
脂肪、血管组织。对照组18例中包括I期8例、11期2例、111期3例、因肿瘤巨
大难以分期5例，均未作穿刺活检所有病例均经手术标本组织学检查证实为肾母
细胞瘤。所有病例均经手术切除标本组织学检查证实为肾母细胞瘤。
2.术前介入治疗(肾动脉栓塞化疗)方法:
利用数字减影血管造影(DsA)设备，采用seldinger技术，腹股沟部经皮穿
刺股动脉，插入猪尾巴导管作腹主动脉造影显示腹主动脉并了解双侧肾动脉走向。
然后以5一6F肾动脉导管(Cobra管)插入肾动脉。注入造影剂证实已进入肾动脉。
了解肿瘤的位置、大小、浸润的范围。经肾动脉造影证实为肾肿瘤后行栓塞化疗。
栓塞乳剂配方为:40%碘化油(或超液碘油)0.sml/kg，阿霉素或表阿霉素20mg/m
(体表面积)，生理盐水5一10ml，必要时(w期)可加入顺铂50mg/mZ(体表面
积)。用注射器将上述药物反复抽吸混成乳剂，缓慢(每分钟lml)注入瘤肾动脉，
透视下见栓塞剂分布至整个肿瘤，将小条明胶海绵与生理盐水一起注入栓塞肾动
脉主干。拔除导管后穿刺部位压迫止血，观察有无穿刺部位出血、穿刺侧下肢血
液循环和足背动脉搏动。手术时间平均92分钟。
2004年浙江大学硕士论文
3.临床观察和随访:
观察TACE后患儿的临床变化包括临床表现、全身情况、白细胞计数、肝肾功
能、心电图，B超比较TACE前后肿瘤大小的变化。B超下肿瘤体积计算方法:V
(ml)=0.523 x L x w xH(L、w、H分别为高、宽、厚的最大值)。以TACE前后
肿瘤体积之差除TACE前的体积的百分比为缩小的比例。比较两组肿瘤完整切除
率及2年无瘤生存率。
4.组织学及免疫组化检查:
栓塞化疗后2一3周手术切除瘤肾。肾母细胞瘤外科手术标本中性缓冲福尔马
林固定，常规取材、脱水、透明、浸蜡、包埋、连续切片4um3张，分别进行HE
染色行肿瘤细胞退变程度检查及PCNA、VEGF免疫组化染色并检查其表达强度。免
疫组化采用PowerVISion”Two一Step试剂盒(MaXim公司)，pCNA、vEGF一抗均为
Antibody oiagnostiCa Inc产品，严格按照说明书操作，设立阳性、阴性对照，
结果分析采用HP工AS一1000高清晰度病理彩色图文分析管理系统。
①肿瘤细胞退变程度的组织学检查，HE染色观察肿瘤细胞形态:按Tepper
Background
Wilms' tumor is one of the most common solid malignancy, and is the first place in renal tumor. It occurs mostly in children under 3 years old. Although there are no obvious symptoms at its early stage, Wilms' tumor growths so rapidly that it is normally difficult to be excised thoroughly and thus the patients have a bad prognosis. As treatment guidelines have established combining surgery, radiotherapy, and chemotherapy, especially preoperative chemotherapy, dramatic improvement has occurred in prognosis of Wilms' tumor, especially in advanced ones. Survival rate of Wilms' tumor increased markedly., Although higher survival rate has acquired in hepatic tumor in adult with the application of transcatherter arterial chemo-embolization (TACE) technique, it is few reported in Wilms tumor. The aim of TACE procedure is to reduce tumor vascularity with a resultant decrease in tumor mass improved tumor contours, easier nephrectomy and minimal intraoperative bleeding, and
the risk of intraoperative malignant cell spillage into the bloodstream that results in the metastasis will be greatly reduced. TACE is also useful in differential the diagnosis.
Proliferating cell nuclear antigen (PCNA) exists in the nucleolus of cell and is an important index to the activity of cell proliferation. Expression of PCNA plays a significant role in the emergence and development of Wilms' tumor.
Vascular endothelial cell factor (VEGF) is one of the most important angiogenic factors that increase vascular permeability. VEGF stimulates capillary formation and has mitogenic effects on vascular endothelial cells. Objective
This content is to study the effect of preoperative transcatherter arterial chemo-embolization on Wilms' tumor, and to know the feasibility of TACE therapy for the children with Wilms' tumor, the side effect, degeneration of tumor cell. The expression of PCNA and VEGF were detected and compared between two groups. Methods
41 cases of Wilms' tumor that were diagnosed after abdominal Ultrasonography (US), computed tomography (CT) and/or intravenous urography IVU examination were collected. The patients were divided into two groups: 23 cases (therapy group) were performed TACE and then operated 2 weeks later. The rest were operated directly without TACE. At the time of diagnosis, six patients were stage I , three were stage III, one was stage IV and the rest were not staged because of too large mass in TACE
group. Eight patients were stage I , nine were stage II, two were stage III,and five patients could not be staged either with the same reason as TACE group in control group. All patients were confirmed by pathological examination of excised tumor.
TACE technique: With the Seldinger percutaneous puncture and catheterization technique, plain abdominal aortography and selective renal arteriography readily perform and reveal the typical finding of pathologic vascularity. They also estimate tumor localization, size and extent of surrounding tissue invasion. Then the renal artery of tumor was embolized with the compound of adrimycin (20mg/m2) , iodized oil (0.5mg/kg) and gelatin sponge. The average time of TACE was 92 minutes. Nephrectomy was performed 2 weeks later.
Clinical observation and following up: clinical symptom, white cell count, liver and kidney function analysis, electrocardiogram and tumor volume change pre- and post-TACE were observed. Whole tumor removal rate and 2-years relapse-free survival rate were compared between two groups.
Histology and immunohistochemistry: to observe the degeneration of tumor cell, such as necrotic, fragmentized and disappeared tumor call according to the Tepper criterion. A comparative analysis of the pathological finding was made in two groups, and monoclonal antibodies were used to detect the expression of PCNA and VEGF in tumor tissue.
Results
1. TACE procedure was succeeded in all two groups without serious side effects. The average time of procedure was 92 minutes. About 2 weeks later shrinkage of tumor volume was 35.6%,
2004年浙江大学硕士论文
肿瘤细胞杀灭作用而全身毒副作用较小。
增殖细胞核抗原(PCNA)存在于细胞核内。静止期细胞内含量极少，增殖细
胞或转化细胞中表达量高，在G!晚期及S期表达量最高，M期末降解消失，是研
究细胞增殖活性的重要指标。PCNA的表达在肿瘤的发生发展中具有重要作用。
肿瘤的生长、肿瘤的转移及转移部位的生长均有赖于肿瘤组织新生血管的生
成，目前己知血管内皮生长因子(VEGF)是参与血管生成的最重要的一种生长因
子。它特异作用于血管内皮细胞，促进内皮细胞的有丝分裂和趋化作用，还增加
血管通透性，使管内的纤维蛋白原等外渗，不仅为内皮细胞迁移和新生毛细血管
网的建立提供必要的基质，也为肿瘤的生长提供良好的基质。
本研究旨在对肾母细胞瘤术前动脉栓塞化疗的方法、疗效、患儿的耐受程度、
毒副反应和作用机理包括肿瘤细胞退变情况、肿瘤细胞的增殖细胞核抗原(PCNA)
和血管内皮生长因子(VEGF)表达的改变等进行研究。进一步提高肾母细胞瘤，
尤其是晚期肾母细胞瘤的疗效。
材料与方法
.病例与分组:
肾母细胞瘤41例。住院后经腹部B超、CT和/或静脉肾盂造影初步诊断为
肾母细胞瘤。分为两组:①TACE组:23例，行术前动脉栓塞化疗，2周左右再行
肿瘤切除术;②对照组:18例，未应用术前动脉栓塞化疗而直接手术切除肿瘤。
2004年浙江大学硕士论文
组织分型按照国际小)匕肿瘤学会(SIOP)和美国Wilms，瘤研究组(NWTS一3)的
分型法分为“预后好的组织结构(FH)”和“预后差的组织结构(UH)”。分期根
据NWTS一3的标准。术前临床分期:TACE组23例包括I期6例、n期O例、m
期9例、W期1例、因肿瘤巨大难以分期7例，其中15例手术前进行细针肿瘤穿
刺活检，13例为良好组织学类型(FH)，1例不良组织学类型(UH)，1例为小片
脂肪、血管组织。对照组18例中包括I期8例、11期2例、111期3例、因肿瘤巨
大难以分期5例，均未作穿刺活检所有病例均经手术标本组织学检查证实为肾母
细胞瘤。所有病例均经手术切除标本组织学检查证实为肾母细胞瘤。
2.术前介入治疗(肾动脉栓塞化疗)方法:
利用数字减影血管造影(DsA)设备，采用seldinger技术，腹股沟部经皮穿
刺股动脉，插入猪尾巴导管作腹主动脉造影显示腹主动脉并了解双侧肾动脉走向。
然后以5一6F肾动脉导管(Cobra管)插入肾动脉。注入造影剂证实已进入肾动脉。
了解肿瘤的位置、大小、浸润的范围。经肾动脉造影证实为肾肿瘤后行栓塞化疗。
栓塞乳剂配方为:40%碘化油(或超液碘油)0.sml/kg，阿霉素或表阿霉素20mg/m
(体表面积)，生理盐水5一10ml，必要时(w期)可加入顺铂50mg/mZ(体表面
积)。用注射器将上述药物反复抽吸混成乳剂，缓慢(每分钟lml)注入瘤肾动脉，
透视下见栓塞剂分布至整个肿瘤，将小条明胶海绵与生理盐水一起注入栓塞肾动
脉主干。拔除导管后穿刺部位压迫止血，观察有无穿刺部位出血、穿刺侧下肢血
液循环和足背动脉搏动。手术时间平均92分钟。
2004年浙江大学硕士论文
3.临床观察和随访:
观察TACE后患儿的临床变化包括临床表现、全身情况、白细胞计数、肝肾功
能、心电图，B超比较TACE前后肿瘤大小的变化。B超下肿瘤体积计算方法:V
(ml)=0.523 x L x w xH(L、w、H分别为高、宽、厚的最大值)。以TACE前后
肿瘤体积之差除TACE前的体积的百分比为缩小的比例。比较两组肿瘤完整切除
率及2年无瘤生存率。
4.组织学及免疫组化检查:
栓塞化疗后2一3周手术切除瘤肾。肾母细胞瘤外科手术标本中性缓冲福尔马
林固定，常规取材、脱水、透明、浸蜡、包埋、连续切片4um3张，分别进行HE
染色行肿瘤细胞退变程度检查及PCNA、VEGF免疫组化染色并检查其表达强度。免
疫组化采用PowerVISion”Two一Step试剂盒(MaXim公司)，pCNA、vEGF一抗均为
Antibody oiagnostiCa Inc产品，严格按照说明书操作，设立阳性、阴性对照，
结果分析采用HP工AS一1000高清晰度病理彩色图文分析管理系统。
①肿瘤细胞退变程度的组织学检查，HE染色观察肿瘤细胞形态:按Tepper
Background
Wilms' tumor is one of the most common solid malignancy, and is the first place in renal tumor. It occurs mostly in children under 3 years old. Although there are no obvious symptoms at its early stage, Wilms' tumor growths so rapidly that it is normally difficult to be excised thoroughly and thus the patients have a bad prognosis. As treatment guidelines have established combining surgery, radiotherapy, and chemotherapy, especially preoperative chemotherapy, dramatic improvement has occurred in prognosis of Wilms' tumor, especially in advanced ones. Survival rate of Wilms' tumor increased markedly., Although higher survival rate has acquired in hepatic tumor in adult with the application of transcatherter arterial chemo-embolization (TACE) technique, it is few reported in Wilms tumor. The aim of TACE procedure is to reduce tumor vascularity with a resultant decrease in tumor mass improved tumor contours, easier nephrectomy and minimal intraoperative bleeding, and
the risk of intraoperative malignant cell spillage into the bloodstream that results in the metastasis will be greatly reduced. TACE is also useful in differential the diagnosis.
Proliferating cell nuclear antigen (PCNA) exists in the nucleolus of cell and is an important index to the activity of cell proliferation. Expression of PCNA plays a significant role in the emergence and development of Wilms' tumor.
Vascular endothelial cell factor (VEGF) is one of the most important angiogenic factors that increase vascular permeability. VEGF stimulates capillary formation and has mitogenic effects on vascular endothelial cells. Objective
This content is to study the effect of preoperative transcatherter arterial chemo-embolization on Wilms' tumor, and to know the feasibility of TACE therapy for the children with Wilms' tumor, the side effect, degeneration of tumor cell. The expression of PCNA and VEGF were detected and compared between two groups. Methods
41 cases of Wilms' tumor that were diagnosed after abdominal Ultrasonography (US), computed tomography (CT) and/or intravenous urography IVU examination were collected. The patients were divided into two groups: 23 cases (therapy group) were performed TACE and then operated 2 weeks later. The rest were operated directly without TACE. At the time of diagnosis, six patients were stage I , three were stage III, one was stage IV and the rest were not staged because of too large mass in TACE
group. Eight patients were stage I , nine were stage II, two were stage III,and five patients could not be staged either with the same reason as TACE group in control group. All patients were confirmed by pathological examination of excised tumor.
TACE technique: With the Seldinger percutaneous puncture and catheterization technique, plain abdominal aortography and selective renal arteriography readily perform and reveal the typical finding of pathologic vascularity. They also estimate tumor localization, size and extent of surrounding tissue invasion. Then the renal artery of tumor was embolized with the compound of adrimycin (20mg/m2) , iodized oil (0.5mg/kg) and gelatin sponge. The average time of TACE was 92 minutes. Nephrectomy was performed 2 weeks later.
Clinical observation and following up: clinical symptom, white cell count, liver and kidney function analysis, electrocardiogram and tumor volume change pre- and post-TACE were observed. Whole tumor removal rate and 2-years relapse-free survival rate were compared between two groups.
Histology and immunohistochemistry: to observe the degeneration of tumor cell, such as necrotic, fragmentized and disappeared tumor call according to the Tepper criterion. A comparative analysis of the pathological finding was made in two groups, and monoclonal antibodies were used to detect the expression of PCNA and VEGF in tumor tissue.
Results
1. TACE procedure was succeeded in all two groups without serious side effects. The average time of procedure was 92 minutes. About 2 weeks later shrinkage of tumor volume was 35.6%,
引文
1．童尔昌，季海萍．小儿腹部外科学[M]．人民卫生出版社411-414．
2．黄澄如．小儿泌尿外科学[M]．山东科学技术出版社330-343．
3. Michael G, Levien MD, Kam A, et al. Postoperative chemotherapy in the National Wilms'Tumor Studies [J]. Semin Urol Oncol. 1999,17 (1):40-45.
4. Lalli AF, Peterson N, Brookstein JJ. Roentgen guided infractions of kidney and lungs, potential therapeutic technic [J]. Radiology.1969,93:434-437.
5．董淳强，杨体泉．肾母细胞瘤术前介入治疗的临床研究进展[J]．儿童肿瘤，2002，1(1)：47-49．
6．李民驹，沈来根，周银宝．小儿巨大肾母细胞瘤术前栓塞化疗[J]．实用肿瘤杂志，1997，12(3)：110-112．
7． 陈方，刘国华，张忠德，等．增殖细胞核抗原在肾母细胞瘤中的表达及其临床意义[J]．中华小儿外科杂志，1997，18(1)：6-7．
8．蒋学武，陈继东，王少洪．小儿肾母细胞瘤中增殖细胞核抗原的表达及其临床意义[J]．中华实验诊断学，2000，4(1)：10-11．
9．袁继炎，李福年，张文．Wilms瘤细胞增殖活性检测及意义[J]．中华实验外科杂志，1999，16(3)：266-268．
10．徐敏，施诚仁，张文竹，等．儿童实体瘤中血管内皮生长因子的表达[J]．中华小儿外科杂志，1999，20(5)：280-282．
11．于启海，郭宗远．血管内皮生长因子的表达与肾母细胞瘤[J]．中华小儿外科杂志，2003，24(1)：90-92．
12．吴后男，李玉林，张丽红，等．血管内皮生长因子和E26转录因子在乳腺癌中的表达及意义[J]．中华病理学杂志，2002，31(3)：222-226．
13. Godzinski J, Tournade ME Dc Kraker J, et al. The role of preoperative chemotherapy in the treatment of nephroblastoma: the SIOP experience [J]. Semin Urol Oncol, 1999,17 (1):28-32.
14. Ritchey M.L. Primary nephrectomy for Wilms'tumor:approach of the National Wilms'Tumor Study Group [J]. Uro. 1996,47 (6):787-791.
15．刘广健，徐辉雄，吕明德，等．三维超声体积自动测量技术测量肝脏肿瘤体积的临床研究[J]．中国超声医学杂志，2003，19(1)：70-73．
16. Tepper M, Vidone RA, Hays MA, et al. Preoperative irradiation in rectal cancer: initial comparison of clinical tolerance, surgical and pathologic findings[J]. Am J Roentgenol Radium Ther Nucl Med. 1968,102(3):587-95.
17．魏光辉，金先庆，李旭良，等．肾母细胞瘤术前化疗前后P-糖蛋白表达的变化及临床意义[J]．重庆医科大学学报，2001，26(1)：34-36．
18．高解春，陈莲，毕允力．术前化疗在肾母细胞瘤的应用及其组织病理观察[J]．中华泌尿外科杂志，1996，17(11)：654-656．
19．魏光辉，金先庆．术前化疗在肾母细胞瘤的应用及研究进展[J]．国外医学：泌尿系统分册，2001，21(2)：96-97．
20. Zupancic B, Bradic I, Batinica S, et al. Our 10-year experience with embolized Wilms'tumor [J]. Eur J Pediatr Surg.1995,5 (2):88-91.
21．李民驹，唐达星，周银宝，等．中晚期肾母细胞瘤术前介入治疗的临床研究[J]．中华小儿外科杂志，2001，22(1)：10-13．
22．李家平，杨建勇，李桂生，等．肾母细胞瘤术前介入治疗的临床病理学研究[J]．中华放射学杂志，2002，36(7)：644-548．
23．李家平，郭文波，杨建勇，等．术前介入治疗对肾母细胞瘤细胞增殖和凋亡的影响[J]．中华小儿外科杂志，2002，23(3)：205-207．
24. Pritchard J, Imeson J, Barnes J, et al. Results of the United Kingdom Children's Cancer Study Group first Wilms'Tumor Study [J]. J Clin Oncol. 1995,13 (1):124-33.
25. Rowe DH, Kayton ML, O'Toole KM, et al. Pathological angiogenesis in a murine model of human Wilms'tumor[J]. J Pediatr Surg. 1999,34(5):676-679.
26. Kayton ML, Rowe DH, O'Toole KM, et al. Metastasis correlates with production of vascular endothelial growth factor in a murine model of human Wilms'tumor, [J] J Pediatr Surg, 1999, 34 (5):743-748.
2．黄澄如．小儿泌尿外科学[M]．山东科学技术出版社330-343．
3. Michael G, Levien MD, Kam A, et al. Postoperative chemotherapy in the National Wilms'Tumor Studies [J]. Semin Urol Oncol. 1999,17 (1):40-45.
4. Lalli AF, Peterson N, Brookstein JJ. Roentgen guided infractions of kidney and lungs, potential therapeutic technic [J]. Radiology.1969,93:434-437.
5．董淳强，杨体泉．肾母细胞瘤术前介入治疗的临床研究进展[J]．儿童肿瘤，2002，1(1)：47-49．
6．李民驹，沈来根，周银宝．小儿巨大肾母细胞瘤术前栓塞化疗[J]．实用肿瘤杂志，1997，12(3)：110-112．
7． 陈方，刘国华，张忠德，等．增殖细胞核抗原在肾母细胞瘤中的表达及其临床意义[J]．中华小儿外科杂志，1997，18(1)：6-7．
8．蒋学武，陈继东，王少洪．小儿肾母细胞瘤中增殖细胞核抗原的表达及其临床意义[J]．中华实验诊断学，2000，4(1)：10-11．
9．袁继炎，李福年，张文．Wilms瘤细胞增殖活性检测及意义[J]．中华实验外科杂志，1999，16(3)：266-268．
10．徐敏，施诚仁，张文竹，等．儿童实体瘤中血管内皮生长因子的表达[J]．中华小儿外科杂志，1999，20(5)：280-282．
11．于启海，郭宗远．血管内皮生长因子的表达与肾母细胞瘤[J]．中华小儿外科杂志，2003，24(1)：90-92．
12．吴后男，李玉林，张丽红，等．血管内皮生长因子和E26转录因子在乳腺癌中的表达及意义[J]．中华病理学杂志，2002，31(3)：222-226．
13. Godzinski J, Tournade ME Dc Kraker J, et al. The role of preoperative chemotherapy in the treatment of nephroblastoma: the SIOP experience [J]. Semin Urol Oncol, 1999,17 (1):28-32.
14. Ritchey M.L. Primary nephrectomy for Wilms'tumor:approach of the National Wilms'Tumor Study Group [J]. Uro. 1996,47 (6):787-791.
15．刘广健，徐辉雄，吕明德，等．三维超声体积自动测量技术测量肝脏肿瘤体积的临床研究[J]．中国超声医学杂志，2003，19(1)：70-73．
16. Tepper M, Vidone RA, Hays MA, et al. Preoperative irradiation in rectal cancer: initial comparison of clinical tolerance, surgical and pathologic findings[J]. Am J Roentgenol Radium Ther Nucl Med. 1968,102(3):587-95.
17．魏光辉，金先庆，李旭良，等．肾母细胞瘤术前化疗前后P-糖蛋白表达的变化及临床意义[J]．重庆医科大学学报，2001，26(1)：34-36．
18．高解春，陈莲，毕允力．术前化疗在肾母细胞瘤的应用及其组织病理观察[J]．中华泌尿外科杂志，1996，17(11)：654-656．
19．魏光辉，金先庆．术前化疗在肾母细胞瘤的应用及研究进展[J]．国外医学：泌尿系统分册，2001，21(2)：96-97．
20. Zupancic B, Bradic I, Batinica S, et al. Our 10-year experience with embolized Wilms'tumor [J]. Eur J Pediatr Surg.1995,5 (2):88-91.
21．李民驹，唐达星，周银宝，等．中晚期肾母细胞瘤术前介入治疗的临床研究[J]．中华小儿外科杂志，2001，22(1)：10-13．
22．李家平，杨建勇，李桂生，等．肾母细胞瘤术前介入治疗的临床病理学研究[J]．中华放射学杂志，2002，36(7)：644-548．
23．李家平，郭文波，杨建勇，等．术前介入治疗对肾母细胞瘤细胞增殖和凋亡的影响[J]．中华小儿外科杂志，2002，23(3)：205-207．
24. Pritchard J, Imeson J, Barnes J, et al. Results of the United Kingdom Children's Cancer Study Group first Wilms'Tumor Study [J]. J Clin Oncol. 1995,13 (1):124-33.
25. Rowe DH, Kayton ML, O'Toole KM, et al. Pathological angiogenesis in a murine model of human Wilms'tumor[J]. J Pediatr Surg. 1999,34(5):676-679.
26. Kayton ML, Rowe DH, O'Toole KM, et al. Metastasis correlates with production of vascular endothelial growth factor in a murine model of human Wilms'tumor, [J] J Pediatr Surg, 1999, 34 (5):743-748.