Tang Xianglian,Liu Denghui,Li Yong.Difficulties and reflections on proper treatments of hepatoblastoma in children[J].Journal of Clinical Pediatric Surgery,2023,22(12):1104-1108.[doi:10.3760/cma.j.cn101785-202310045-002]
儿童肝母细胞瘤治疗难点与思考
- Title:
- Difficulties and reflections on proper treatments of hepatoblastoma in children
- Keywords:
- Hepatoblastoma; Chemoradiotherapy; Adjuvant; Surgical Procedures; Operative; Therapy; Child
- 摘要:
- 肝母细胞瘤(hepatoblastoma,HB)是儿童最常见的肝脏恶性肿瘤。化疗和手术仍然是HB治疗的基础。近年来,临床上对于HB的诊治能力已有显著提升,但仍然面临着诸多难点与挑战。本文从化疗药物与化疗方式的选择、肿瘤R0切除及其必要性思考、无法常规手术切除患儿的治疗探索、肝移植时机选择、转移和复发HB的治疗五个方面进行探讨,并对目前HB患儿治疗结局进行总结,供临床治疗与研究工作参考。
- Abstract:
- Hepatoblastoma (HB) has been the most common type of liver malignancy in children.Chemotherapy and surgery are still important treatments of HB.In recent years,clinical diagnoses and treatments of HB have significantly improved.However,many practical challenges persist.This review focused upon selecting chemotherapeutic agents and modalities,R0 (microscopically margin-negative) tumor resection and its necessity,handling inoperable cases,timing of liver transplantation and managements of metastatic and relapsing HB.
参考文献/References:
[1] Hafberg E,Borinstein SC,Alexopoulos SP.Contemporary management of hepatoblastoma[J].Curr Opin Organ Transplant,2019,24(2):113-117.DOI:10.1097/MOT.0000000000000618.
[2] 儿童肝母细胞瘤诊疗规范(2019年版)编写审定专家组.儿童肝母细胞瘤诊疗规范(2019年版)[J].临床肝胆病杂志,2019,35(11):2431-2434.DOI:10.3969/j.issn.1001-5256.2019.11.008. Expert Group for Drafting and Approving Guidelines for Diagnosing and Treating Hepatoblastoma (2019 Edition):Guidelines for Diagnosing and Treating Hepatoblastoma (2019)[J].J Clin Hepatol,2019,35(11):2431-2434.DOI:10.3969/j.issn.1001-5256.2019.11.008.
[3] Hou JY,Yeh TC,Huang TH,et al.A retrospective study of clinical features and outcome in patients with refractory or recurrent hepatoblastoma:a single institution experience[J].Pediatr Neonatol,2021,62(4):400-405.DOI:10.1016/j.pedneo.2021.03.018.
[4] Tian Y,Chen XH,Yu F,et al.Neoadjuvant chemotherapy or upfront surgery in hepatoblastoma:a multicenter retrospective study[J].Pediatr Blood Cancer,2023,70(9):e30470.DOI:10.1002/pbc.30470.
[5] Hu HM,Zhang WL,Li J,et al.Clinical application of irinotecan combined with first-line chemotherapeutics against pediatric hepatoblastoma with pulmonary metastasis[J].Pak J Pharm Sci,2022,35(5):1301-1306.
[6] Zhang YT,Feng LH,Zhong XD,et al.Vincristine and irinotecan in children with relapsed hepatoblastoma:a single-institution experience[J].Pediatr Hematol Oncol,2015,32(1):18-25.DOI:10.3109/08880018.2014.909913.
[7] Thompson PA,Malogolowkin MH,Furman WL,et al.Vincristine/irinotecan/temsirolimus upfront window treatment of high-risk hepatoblastoma:a report from the Children’s Oncology Group AHEP0731 Study Committee[J].Pediatr Blood Cancer,2023,70(7):e30365.DOI:10.1002/pbc.30365.
[8] Hu HM,Zhang WL,Zhang Y,et al.Individualized chemotherapy and efficacy analysis of hepatoblastoma in children[J].Pediatr Blood Cancer,2024,71(1):e30693.DOI:10.1002/pbc.30693.
[9] Failli M,Demir S,Del Río-?lvarez ?,et al.Computational drug prediction in hepatoblastoma by integrating pan-cancer transcriptomics with pharmacological response[J/OL].Hepatology,2023.https://doi.org/10.1097/hep.0000000000000601.DOI:10.1097/HEP.0000000000000601.
[10] Jiang YZ,Zhou SY,Shen G,et al.Microwave ablation combined with transcatheter arterial chemoembolization is effective for treating unresectable hepatoblastoma in infants and children[J].Medicine (Baltimore),2018,97(42):e12607.DOI:10.1097/MD.0000000000012607.
[11] Tang XL,He XB,Jiang H.Efficacy and safety of HIFU in combination with TACE in unresectable pediatric HB:a randomized,controlled,single-center clinical trial[J].Medicine (Baltimore),2022,101(48):e32022.DOI:10.1097/MD.0000000000032022.
[12] 中国抗癌协会肝癌专业委员会.肝动脉灌注化疗治疗肝细胞癌中国专家共识(2021版)[J].中华消化外科杂志,2021,20(7):754-759.DOI:10.3760/cma.j.cn115610-20210618-00288. Chinese Society of Liver Cancer,China Anti-Cancer Association:Chinese Expert Consensus on Hepatic Arterial Infusion Chemotherapy for Hepatocellular Carcinoma (2021 Edition)[J].Chin J Dig Surg,2021,20(7):754-759.DOI:10.3760/cma.j.cn115610-20210618-00288.
[13] Liu S,Feng J,Ren QH,et al.Evaluating the clinical efficacy and limitations of indocyanine green fluorescence-guided surgery in childhood hepatoblastoma:a retrospective study[J].Photodiagnosis Photodyn Ther,2023,44:103790.DOI:10.1016/j.pdpdt.2023.103790.
[14] Paraboschi I,De Coppi P,Stoyanov D,et al.Fluorescence imaging in pediatric surgery:state-of-the-art and future perspectives[J].J Pediatr Surg,2021,56(4):655-662.DOI:10.1016/j.jpedsurg.2020.08.004.
[15] Meyers RL,Tiao G,de Ville de Goyet J,et al.Hepatoblastoma state of the art:pre-treatment extent of disease,surgical resection guidelines and the role of liver transplantation[J].Curr Opin Pediatr,2014,26(1):29-36.DOI:10.1097/MOP.0000000000000042.
[16] Yang TY,Whitlock RS,Vasudevan SA.Surgical management of hepatoblastoma and recent advances[J].Cancers (Basel),2019,11(12):1944.DOI:10.3390/cancers11121944.
[17] Aronson DC,Weeda VB,Maibach R,et al.Microscopically positive resection margin after hepatoblastoma resection:what is the impact on prognosis? A Childhood Liver Tumours Strategy Group (SIOPEL) report[J].Eur J Cancer,2019,106:126-132.DOI:10.1016/j.ejca.2018.10.013.
[18] Ren XH,Li HB,Diao M,et al.Impact of microscopically margin-positive resection on survival in children with hepatoblastoma after hepatectomy:a retrospective cohort study[J].Int J Clin Oncol,2020,25(4):765-773.DOI:10.1007/s10147-019-01573-0.
[19] Fuchs J,Murtha-Lemekhova A,Rabaux-Eygasier L,et al.Evidence on indications and techniques to increase the future liver remnant in children undergoing extended hepatectomy:a systematic review and meta-analysis of individual patient data[J].Front Pediatr,2022,10:915642.DOI:10.3389/fped.2022.915642.
[20] 姚伟,董岿然,肖现民,等.联合肝脏离断和门静脉结扎二步肝切除术治疗儿童肝母细胞瘤一例报告[J].中华小儿外科杂志,2018,39(8):597-603.DOI:10.3760/cma.j.issn.0253-3006.2018.08.009. Yao W,Dong KR,Xiao XM,et al.Associating liver partition and portal vein ligation for staged hepatectomy for hepatoblastoma:a report of one case[J].Chin J Pediatr Surg,2018,39(8):597-603.DOI:10.3760/cma.j.issn.0253-3006.2018.08.009.
[21] Wu YH,Zeng LX,Qiu RL,et al.Two-stage laparoscopic resection of giant hepatoblastoma in infants combined with liver partial partition and artery ligation[J].World J Surg Oncol,2021,19(1):63.DOI:10.1186/s12957-021-02156-y.
[22] 余辉,郑百俊,高亚,等.全腹腔镜ALPPS治疗小儿巨块型肝脏肿瘤[J].临床小儿外科杂志,2021,20(7):635-640,657.DOI:10.12260/lcxewkzz.2021.07.008. Yu H,Zheng BJ,Gao Y,et al.Total laparoscopic ALPPS in the treatment of massive liver tumor[J].J Clin Ped Sur,2021,20(7):635-640,657.DOI:10.12260/lcxewkzz.2021.07.008.
[23] Cai YL,Song PP,Tang W,et al.An updated systematic review of the evolution of ALPPS and evaluation of its advantages and disadvantages in accordance with current evidence[J].Medicine (Baltimore),2016,95(24):e3941.DOI:10.1097/MD.0000000000003941.
[24] Ye QF,Zeng C,Wang YF,et al.Long-term outcomes of ante-situm resection and auto-transplantation in conventionally unresectable hepatocellular carcinoma:a single-center experience[J].Ann Transplant,2018,23:81-88.DOI:10.12659/aot.905983.
[25] 康权,李英存,戴小科,等.体外循环辅助下半离体肝切除自体肝移植治疗儿童复杂肝脏肿瘤[J].中华小儿外科杂志,2018,39(10):725-728.DOI:10.3760/cma.j.issn.0253-3006.2018.10.002. Kang Q,Li YC,Dai XK,et al.Ex vivo hepatic resection and autotransplantation with cardiopulmonary bypass for hepatoblastoma in children:one case report[J].Chin J Pediatr Surg,2018,39(10):725-728.DOI:10.3760/cma.j.issn.0253-3006.2018.10.002.
[26] Hibi T,Rela M,Eason JD,et al.Liver transplantation for colorectal and neuroendocrine liver metastases and hepatoblastoma.Working group report from the ILTS transplant oncology consensus conference[J].Transplantation,2020,104(6):1131-1135.DOI:10.1097/TP.0000000000003118.
[27] Tang MJ,Ma XL,He XL,et al.A multicenter prospective study on the management of hepatoblastoma in children:a report from the Chinese Children’s Cancer Group[J/OL].World J Pediatr,2023,1-12.https://doi.org/10.1007/s12519-023-00750-6.DOI:10.1007/s12519-023-00750-6.
[28] Uchida H,Sakamoto S,Kasahara M,et al.An analysis of the outcomes in living donor liver transplantation for pediatric malignant hepatic tumors using nationwide survey data in Japan[J].Transpl Int,2021,34(8):1408-1421.DOI:10.1111/tri.13924.
[29] Boster JM,Superina R,Mazariegos GV,et al.Predictors of survival following liver transplantation for pediatric hepatoblastoma and hepatocellular carcinoma:experience from the Society of Pediatric Liver Transplantation (SPLIT)[J].Am J Transplant,2022,22(5):1396-1408.DOI:10.1111/ajt.16945.
[30] Xie HW,Liu G,Shen Z,et al.Surgical resection of chemotherapy-insensitive pulmonary metastases in children with hepatoblastoma in China:a single-center experience[J].J Cancer Res Ther,2022,18(5):1387-1391.DOI:10.4103/jcrt.jcrt_1992_21.
[31] Wu PV,Rangaswami A.Current approaches in hepatoblastoma-new biological insights to inform therapy[J].Curr Oncol Rep,2022,24(9):1209-1218.DOI:10.1007/s11912-022-01230-2.
[32] Lake CM,Bondoc AJ,Dasgupta R,et al.Indocyanine green is a sensitive adjunct in the identification and surgical management of local and metastatic hepatoblastoma[J].Cancer Med,2021,10(13):4322-4343.DOI:10.1002/cam4.3982.
[33] Li F,Zhang WL,Hu HM,et al.Factors influencing recurrence after complete remission in children with hepatoblastoma:a 14-year retrospective study in China[J].PLoS One,2021,16(11):e0259503.DOI:10.1371/journal.pone.0259503.
[34] Hiyama E,Hishiki T,Watanabe K,et al.Outcome and late complications of hepatoblastomas treated using the Japanese study group for pediatric liver tumor 2 protocol[J].J Clin Oncol,2020,38(22):2488-2498.DOI:10.1200/JCO.19.01067.
[35] 李潇然,叶进冬,赵頔,等.再次肝切除治疗复发性儿童肝母细胞瘤[J].中华普通外科杂志,2022,37(5):366-367.DOI:10.3760/cma.j.cn113855-20210616-00364. Li XR,Ye JD,Zhao D,et al.Re-hepatectomy for recurrent childhood hepatoblastoma[J].Chin J Gen Surg,2022,37(5):366-367.DOI:10.3760/cma.j.cn113855-20210616-00364.
[36] Takahashi N,Yamada Y,Hoshino K,et al.Living donor liver re-transplantation for recurrent hepatoblastoma in the liver graft following complete eradication of peritoneal metastases under indocyanine green fluorescence imaging[J].Cancers (Basel),2019,11(5):730.DOI:10.3390/cancers11050730.
相似文献/References:
[1]陈立才,李朋飞,黄一敏,等. 抗EpCAM单克隆抗体治疗肝母细胞瘤的动物实验研究[J].临床小儿外科杂志,2019,18(01):63.
Chen Licai,Li Pengfei,Huang Yimin,et al. Targeting therapy of antiEpCAM monoclonal antibody in hepatoblastoma animal model.[J].Journal of Clinical Pediatric Surgery,2019,18(12):63.
[2]成英杰,单慈,石寒菡,等.MicroRNAs在肝母细胞瘤诊断、鉴别诊断及预后评估中的研究进展[J].临床小儿外科杂志,2019,18(08):660.[doi:10.3969/j.issn.1671-6353.2019.08.009]
Cheng Yingjie,Shan Ci,Shi Hanhan,et al.Research advances of MicroRNAs in the diagnosis,differential diagnosis and prognostic evaluation of hepatoblastoma[J].Journal of Clinical Pediatric Surgery,2019,18(12):660.[doi:10.3969/j.issn.1671-6353.2019.08.009]
[3]王焕民.重视安全与历练,提高小儿肝胆肿瘤诊治水平[J].临床小儿外科杂志,2023,22(12):1101.[doi:10.3760/cma.j.cn101785-202310061-001]
Wang Huanmin.Further improving the diagnoses and treatments of pediatric hepatobiliary tumors[J].Journal of Clinical Pediatric Surgery,2023,22(12):1101.[doi:10.3760/cma.j.cn101785-202310061-001]
[4]林宇,王焕民,杨深,等.经导管动脉栓塞术治疗肝母细胞瘤破裂的初步探索[J].临床小儿外科杂志,2023,22(12):1109.[doi:10.3760/cma.j.cn101785-202310011-003]
Lin Yu,Wang Huanmin,Yang Shen,et al.Preliminary exploration of transcatheter arterial embolization for ruptured hepatoblastoma[J].Journal of Clinical Pediatric Surgery,2023,22(12):1109.[doi:10.3760/cma.j.cn101785-202310011-003]
[5]徐晓钢,曾纪晓,罗媛圆,等.全球首例不阻断第一肝门的机器人肝切除术治疗儿童肝母细胞瘤[J].临床小儿外科杂志,2023,22(12):1114.[doi:10.3760/cma.j.cn101785-202307016-004]
Xu Xiaogang,Zeng Jixiao,Luo Yuanyuan,et al.Robotic hepatectomy in a 14-month-old child of hepatoblastoma without the first hepatic portal control:a first case report in the world[J].Journal of Clinical Pediatric Surgery,2023,22(12):1114.[doi:10.3760/cma.j.cn101785-202307016-004]
[6]刘百慧,解鲁璐,姚伟,等.联合肝脏离断和门静脉结扎二步肝切除术治疗儿童巨大肝母细胞瘤[J].临床小儿外科杂志,2023,22(12):1119.[doi:10.3760/cma.j.cn101785-202309028-005]
Liu Baihui,Xie Lulu,Yao Wei,et al.Application of associating liver partition and portal vein ligation during two-stage hepatectomy for massive hepatoblastoma[J].Journal of Clinical Pediatric Surgery,2023,22(12):1119.[doi:10.3760/cma.j.cn101785-202309028-005]
[7]杨丽媛,顾松,王晶,等.m6A修饰在肝母细胞瘤中的研究进展[J].临床小儿外科杂志,2023,22(12):1130.[doi:10.3760/cma.j.cn101785-202209040-007]
Yang Liyuan,Gu Song,Wang Jing,et al.Research advances of m6A modification in hepatoblastoma[J].Journal of Clinical Pediatric Surgery,2023,22(12):1130.[doi:10.3760/cma.j.cn101785-202209040-007]
[8]周恩卿,董瑞.黄连素在儿童胚胎源性肿瘤中的研究进展[J].临床小儿外科杂志,2023,22(12):1135.[doi:10.3760/cma.j.cn101785-202208042-008]
Zhou Enqing,Dong Rui.Research advances of berberine in pediatric embryonal tumors[J].Journal of Clinical Pediatric Surgery,2023,22(12):1135.[doi:10.3760/cma.j.cn101785-202208042-008]
[9]姚伟,宋治莹,杨家健,等.单侧肾母细胞瘤新辅助化疗后保留肾单位手术的初步疗效分析[J].临床小儿外科杂志,2024,(04):372.[doi:10.3760/cma.j.cn101785-202403060-013]
Yao Wei,Song Zhiyin,Yang Jiajian,et al.Preliminary analysis of nephron sparing surgery for unilateral Wilms tumor after neoadjuvant chemotherapy[J].Journal of Clinical Pediatric Surgery,2024,(12):372.[doi:10.3760/cma.j.cn101785-202403060-013]
[10]杨维,刘珊,任清华,等.多灶性肝母细胞瘤手术切除的单中心研究[J].临床小儿外科杂志,2024,(06):543.[doi:10.3760/cma.j.cn101785-202310006-007]
Yang Wei,Liu Shan,Ren Qinghua,et al.Hepatectomy for multifocal hepatoblastoma:a single-center report[J].Journal of Clinical Pediatric Surgery,2024,(12):543.[doi:10.3760/cma.j.cn101785-202310006-007]
备注/Memo
收稿日期:2023-10-25。
基金项目:湖南省自然科学基金-面上项目(2023JJ30323); 2022年湖南省卫生健康高层次人才-医学学科青年骨干人才(09260); 湖南省儿童实体瘤临床医学研究中心(2023SK4058); 湖南省临床医疗技术创新引导项目(2020SK50501)
通讯作者:李勇,Email:liyongpuwaike@163.com