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.     

介入栓塞治疗后手术切除肝母细胞瘤

目的 评价介入栓塞对肝母细胞瘤的手术切除率及预后的影响.方法 回顾性分析2006年1月至2011年12月介入栓塞后经手术治疗的肝母细胞瘤33例患儿的临床资料.本组术前予介入栓塞治疗2～4个疗程后,均可手术切除,术后2周均予辅助化疗.结果 所有病例均获得肿瘤的完整切除,手术效果良好,术后随访6个月～5年,存活30例.结论 术前介入栓塞治疗可减少肿瘤血供,缩小肿瘤体积,提高手术切除率,综合治疗后可提高生存率.     

Cure of hepatoblastoma with transcatheter arterial chemoembolization

Until now surgical resection was still considered as the only choice of successful treatment of hepatoblastoma. Therefore, successful use of transcatheter arterial chemoembolization (TACE) alone to cure the unresectable hepatoblastoma in an infant was firstly reported. A 6-month-old boy presented with a huge abdominal mass and was found to have a hepatoblastoma of 17.5 cm x 11.5 cm x 10 cm on computed tomography (CT) scan. The serum alpha-fetoprotein (AFP) was elevated to 6250 ng/mL. On the first TACE the main feeding arteries were completely occluded by stainless steel embolization coils. After one month tumor shrinkage was 75%, but a newly formed feeding artery was found and embolized on second TACE. Since the third TACE no newly formed feeding artery was found and 6 courses of intravenous chemotherapy were consolidated. On the last DSA and CT the tumor was completely disappeared and AFP returned to normal. During the follow-up he remained disease-free for 33 months until the present report. TACE may provide an additional promising choice in the treatment of hepatoblastoma.     

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     

Hepatic arterial chemoembolization as an initial treatment for hepatoblastoma

Hepatic arterial chemoembolization using Lipiodol Ultra-fluid (Laboratoire Guerbet), doxorubicin HCl, and Gelfoam (Upjohn)(L-TAE) produced good results in an infant with a hepatoblastoma initially considered to be difficult to resect. Lipiodol selectively accumulated in the tumor, and a marked reduction in tumor size with decrease of alpha-fetoprotein was observed. One month after L-TAE, left hepatectomy was performed uneventfully with a good postoperative course. L-TAE appears to be a useful treatment for hepatoblastoma. Offprint requests to: I. Yamagiwa     

Preliminary experience with arterial chemoembolization for hepatoblastoma and hepatocellular carcinoma in children

The objective of this work was to test feasibility and efficacy of hepatic artery chemoembolization (HACE) in unresectable malignant liver tumors. Five patients aged from 1-12 years were treated in the Medical University of Gdansk from 1999 to 2002. All had locally advanced tumors, which did not respond to systemic chemotherapy: four, hepatoblastoma (HB) and one, hepatocellular carcinoma (HCC). Arteriography was performed and chemoembolization suspension (cisplatin + doxorubicin + mitomycin mixed with lipiodol) was injected, followed by gelatin foam particles. The procedure was performed one to three times in each patient. In four patients (three, HB, one, fibrolamellar HCC), tumor response was observed, with decrease in the diameter of the mass of 25-33% and fall in the AFP level of 83-99%. One child with HB was non-evaluable due to early death caused by systemic myelotoxicity. Two patients (2 HB) underwent macroscopically complete tumor resection, 1 is alive and well, and 1 died at the end of surgery for an unknown reason (possibly related to cardiotoxicity of earlier systemic chemotherapy). One HB patient was successfully transplanted after two HACE courses. The only HCC patient died because of pulmonary oil embolism immediately after the third HACE course. HACE can lead to tumor regression in most cases and may be considered an alternative for patients with unresectable liver tumors who do not respond to primary systemic chemotherapy and are not candidates for liver transplantation for various reasons.     

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。     

Combination chemotherapy and chemoembolization in the treatment of primary inoperable hepatoblastoma

A 33 months old girl and a 5 months old boy presented with unresectable hepatoblastoma (group III) and were treated with combination chemotherapy using Adriamycin, Cyclophosphamide, Cisplatinum (regimen I) and Adriamycin, Etoposide, Cisplatinum (regimen II). In both patients tumor size and alpha-fetoprotein levels decreased remarkably. Tumor regression was considerably enhanced by selective chemoembolization (Ethibloc, Adriamycin) of the right hepatic artery in one patient. After preoperative chemotherapy hepatoblastomas could be removed surgically. Local recurrence in the older patient was treated again successfully by surgery and chemotherapy. The patients are surviving disease-free 17 and 28 months from diagnosis. The efficacy of the treatment warrants prospective clinical trials in patients with unresectable hepatoblastoma.     

Metastatic paraganglioma and paraneoplastic-induced anemia in an adolescent: treatment with hepatic arterial chemoembolization

Mediastinal paragangliomas are rare neoplasms in children. Anemia, as a paraneoplastic syndrome, has been described in adults with metastatic paraganglioma. The management of paraneoplastic anemia from metastatic paraganglioma has been problematic, with no reports in the literature describing successful treatment. This article describes a 17-year-old Jehovah's Witness with a mediastinal paraganglioma, hepatic metastases, and severe anemia. The patient and his family refused blood products and the anemia was refractory to erythropoietin and elemental iron therapy. Serial chemoembolization of the hepatic lesions resulted in resolution of the anemia, allowing subsequent debulking of the mediastinal paraganglioma.     

Neoadjuvant chemotherapy before surgery of hepatoblastoma

Though surgical resection is the main stay of treatment for childhood hepatoblastoma (HB), many are unsuitable for radical surgery at diagnosis due to extensive intrahepatic and/or extra hepatic disease. We report experience in five patients of HB from a single institution (2001–2005) with preoperative Neoadjuvant chemotherapy (NACT) followed by surgery. Three patients received cisplatin, doxorubicin; and two cisplatin/vincristine/5-fluorouracil. All showed more than 50% reduction in tumor size confirmed by CT scan. Hepatic resection R0 was performed in all. There was no chemotherapy related toxicity nor post surgical morbidity or mortality. All are disease free at median follow up of 4 years. NACT produces adequate down staging of the HB with acceptable toxicity. Though cisplatin with doxorubicin produced good results, new protocol with cisplatin, vincristine and 5FU is promising without cardiotoxicity.     

Surgical treatment of hepatoblastoma

Surgical resection remains the cornerstone of cure in hepatoblastoma (HB). Meticulous review of contrast enhanced CT/MR imaging facilitates PRETEXT and POST‐TEXT grouping to determine optimal timing and desired extent of liver resection. Excellent knowledge of liver anatomy is essential and the dissection must ensure protection of the vascular inflow and outflow to the remaining liver at all times. Referral to a liver specialty center in advanced cases may facilitate resectability. Potential surgical complications include bleeding, vascular injury, cardiac arrest, liver failure, and bile leak. The risk of complications can be minimized with preoperative planning, appropriate referral, and precise surgical technique. Pediatr Blood Cancer 2012; 59: 800–808. © 2012 Wiley Periodicals, Inc.     

Successful treatment of multifocal unresectable hepatoblastoma with chemotherapy only

We report the case of a girl with multi-focal hepatoblastoma in whom chemotherapy alone has resulted in long term event-free survival and possibly cure, without any surgical procedure apart from biopsy for initial diagnosis. At presentation she had a large tumour arising from the left lobe of liver and two other separate masses were noted in the right lobe, but the lungs were free of metastases. Histology showed a foetal type of hepatoblastoma. The serum alpha-feto protein (AFP) level was 44,000 iu/litre. Chemotherapy was started using the triple drug regime recommended for “high risk” (of relapse) patients in the SIOPEL 2 hepatoblastoma protocol of the International Society of Paedaitric Oncology (SIOP). Within a few weeks her abdominal girth decreased, the child became much more comfortable. Drug-induced cardiotoxicity, ototoxicity and nephrotoxicity were not observed. After a total of 4 courses of chemotherapy (completed at the end of August 1998) a CT scan showed that all 3 tumours were smaller but that there were residual multifocal defects in the liver neither hepatic resection nor liver transplantation were considered safe or appropriate. 6.5 years after completion of chemotherapy and now aged 8.5 years the child is in normal health and at school with normal liver size, serum AFP levels and chest imaging.     

102例儿童肝母细胞瘤的治疗及预后分析

目的分析儿童肝母细胞瘤(HB)手术结合化疗的疗效及预后,了解风险因素对预后的影响。方法 2006年9月-2014年6月北京同仁医院收治HB患儿102例。男55例,女47例。通过分析临床资料,研究HB的临床疗效及预后。结果 102例患儿经综合治疗后完全缓解(CR)52例占51.0%,部分缓解(PR)20例占19.6%,死亡28例占27.4%,进展2例(2.0%)。随访至2015年1月1日,平均随访时间27.54±19.95个月,2年总生存率(0S)76.5%,3年无事件生存(EFS)60.5%。对随访时间超过12个月的81例患儿进行Kaplan-Meier生存分析,5年平均生存时间71.1个月,95%可信区间61.2~80.9个月。结论儿童HB经规律化疗结合手术治疗后疗效肯定,但应对PLT、反复复发以及远处转移病例加强随访预防复发。     

肝母细胞瘤多学科治疗方案的研究进展

肝母细胞瘤(hepatoblastoma,HB)是胚胎性肿瘤的一种,恶性程度较高,好发于3岁以下儿童。手术切除为HB首选治疗方案,手术切除的完整性关系到肿瘤预后。HB对化疗敏感,可辅助化疗、放疗等治疗手段。目前主流化疗方案为C5V(cisplatin+5-Fluorouracil+vincristine,顺铂+5-氟尿嘧啶+长春新碱)方案。对难治性HB可实施肝移植,且自体肝移植术在临床上已有成功案例。此外,靶向治疗(如针对NK1R及PI3K/Akt等通路的靶向药物治疗)已进入临床试验,而免疫治疗尚处于研发阶段。     

Surgical treatment of hepatoblastoma in children

Hepatoblastoma is the most common liver malignancy in children. With rare exceptions, complete tumour resection is required to cure the patient. Radical tumour resection can be obtained either with standard partial hepatectomy or orthotopic liver transplantation. At present, the surgical approach to hepatoblastoma differs significantly between treatment groups in different parts of the world. Our aim was to review current surgical policy in hepatoblastoma. All aspects of surgery in hepatoblastoma are discussed, including biopsy, tumour resection principles, modern achievements in the field of liver surgery, and the indications and potential contraindications for liver transplantation. Every effort should be made to resect hepatoblastoma completely either by standard partial hepatectomy or by the use of liver transplantation in difficult or clearly unresectable cases.     

Novel therapeutic approaches in the treatment of children with hepatoblastoma

Hepatoblastoma is the most common liver tumor diagnosed in children. Children with persistently unresectable disease, metastatic disease at presentation, recurrent disease, or slowly declining alpha-fetoprotein levels are at high risk for recurrence, exhibit an extremely poor prognosis, and are in desperate need of novel therapeutic agents and strategies. Four high-risk patients were treated. One patient with a local recurrence was treated with irinotecan followed by orthotopic liver transplant. Three patients were treated with tandem high-dose chemotherapy (HDT) with autologous stem cell rescue (two with primary metastatic disease and one with recurrent disease). All three of the patients treated with HDT had relapse (two of them subsequently received irinotecan); the remaining patient underwent surgical resection of a solitary recurrent pulmonary metastasis. Irinotecan demonstrated significant antitumor effects in all three treated patients and was well tolerated. None of the three patients treated with HDT remained disease-free, although the patient who underwent surgical resection of a solitary recurrent pulmonary metastasis remains disease-free 6 years from diagnosis. Further exploration of the use of irinotecan is warranted in high-risk patients with hepatoblastoma.     

Intrahepatic arterial injections of cisplatin-phosphatidylcholine-Lipiodol suspension in two unresectable hepatoblastoma cases

Two cases with unresectable hepatoblastoma were treated by intrahepatic arterial injections of cisplatin-phosphatidylcholine-Lipiodol suspension (CPLS), combined with systemic chemotherapy. Unfortunately, the first patient who was given three injections of CPLS in association with systemic chemotherapy died of progressive disease 18 months after the commencement of the therapy. However, the second patient who received about 1 year of systemic chemotherapy followed by three injections of CPLS prior to subtotal tumor resection, plus four injections after surgery, is now alive and healthy 22 months after the commencement of treatment, with no detectable serum alpha-fetoprotein (AFP), although the AFP level on admission was 695,000 ng/ml. In the surgical specimens of case 2, there were areas with Lipiodol deposits rich in platinum and replaced by marked fibrosis around necrotic tumor nodules. Intrahepatic arterial injection of CPLS in combination with systemic chemotherapy and surgery should be considered as an effective method for unresectable cases.