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     

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。     

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.     

Treatment of unresectable hepatoblastoma with cisplatin,vincristin and 5-fluorouracil

We here describe a 2.5 year old boy with a virilizing unresectable hepatoblastoma. Administration of cisplatin in combination with vincristine and 5-fluorouracil every third week was shown to be very effective and rendered the tumour resectable.Abbreviations AFP alpha-fetoprotein - hCG human chorion gonadotropin - 5-FU 5-fluorouracil     

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。     

复发肝母细胞瘤的治疗进展

复发肝母细胞瘤依然是治疗的难点.本文介绍了肝母细胞瘤复发时的特点,包括复发部位、复发率、肿瘤复发相关的危险因素.同时重点介绍复发肿瘤的治疗方法,包括不同复发部位的肿瘤再手术、化疗、放疗、靶向治疗等,综述了这些治疗措施的临床应用或实验室研究进展,并分别比较了各种治疗方法的有效率.     

Percutaneous radiofrequency ablation for treatment of hepatoblastoma recurrence

Radiofrequency ablation (RFA) has been widely reported as a minimally invasive treatment for liver tumours in adults, but has not been documented as a treatment for hepatoblastoma in a child. We report a 2-year-old boy with local recurrence of hepatoblastoma after partial hepatectomy. Percutaneous RFA was performed under real-time sonographic guidance. There was no imaging evidence of recurrence after a follow-up of 2 years. We consider this a promising technique in children.     

Positron emission tomography in recurrent hepatoblastoma

Early detection of recurrent hepatoblastoma is not always possible with conventional imaging methods such as computed tomography (CT) and magnetic resonance imaging (MRI). This article describes three cases of recurrent hepatoblastoma in which positron emission tomography (PET) using F¹⁸-fluoro-deoxy-glucose (FDG-PET) was used to locate the site of recurrence. In the first two patients, FDG-PET accurately located recurrent disease where it was not detected by conventional imaging modalities, including CT and MRI. In the third patient, FDG-PET imaging also located the recurrent disease in an MRI-identified adrenal metastasis. The technique of coregistration using PET with CT and MRI scans was used in the cases described. This improves the anatomical localization of metabolically active sites and was particularly useful for determining the surgical approach. The difficulties of conventional imaging in locating early tumor recurrence or metastatic disease in hepatoblastoma make FDG-PET imaging an important investigation that may impact patient management.     

Recurrent hepatoblastoma with localization by PET-CT

Hepatoblastoma is the most common primary liver tumor in children, accounting for 79% of pediatric liver malignancies in children younger than 15 years, with most cases reported before the age of 5 years. Localization of primary and recurrent disease is necessary for appropriate clinical decision-making and treatment. We present a case of recurrent hepatoblastoma heralded by rising alpha-fetoprotein levels. After unsuccessful localization by conventional CT and MRI, positron emission tomography CT imaging localized the sites of recurrence.     

Hemoperitoneum as the presenting sign of hepatoblastoma in a newborn

Hepatoblastoma is rarely diagnosed in the neonatal period. We report a neonate in whom massive hemoperitoneum was the presenting sign of hepatoblastoma: tumor injury during vaginal delivery resulted in tumor spread and hemoperitoneum leading to conservative surgical treatment. The authors propose that in cases where intrauterine ultrasonographic findings suggest a hepatic mass, cesarean section should be considered in order to improve the prognosis in cases of congenital hepatoblastoma.     

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.     

Radiological staging in children with hepatoblastoma

Hepatoblastoma is the most common malignant liver tumour of childhood. Accurate radiological staging is very important, especially in children who are treated according to the protocols of the International Childhood Liver Tumor Strategy Group (SIOPEL). These protocols use risk stratification, based almost entirely on imaging findings, to minimize the treatment for localized tumours and to intensify treatment for extensive tumours and those with extrahepatic spread.     

Renal function following liver transplantation for unresectable hepatoblastoma

Combination of cyclosporine (CsA) and tacrolimus immunosuppression post-liver transplantation (LT) and the chemotherapeutic drugs used to treat hepatoblastoma (HB), are nephrotoxic. We aimed to determine the severity and duration of nephrotoxicity in children following LT for unresectable HB. We reviewed all children undergoing LT for unresectable HB at the Liver Unit, Birmingham Children's Hospital, UK, from 1991 to July 2000. Thirty-six children undergoing LT for biliary atresia, matched for age and sex, were selected as controls to compare pre- and post-LT renal function. Renal function was determined by estimation of glomerular filtration rate (eGFR) derived from plasma creatinine using Schwartz's formula. Twelve children with HB (mean age of diagnosis 33 months) who underwent LT (mean age 47 months) and 36 controls (mean age of LT 34 months) were studied. CsA was the main immunosuppressive drug used in each group. The median eGFR before, and at 3, 6, 12, 24 and 36 months after LT in HB group was significantly lower than controls (93 vs. 152, 66 vs. 79, 62 vs. 86, 66 vs. 87, 64 vs. 94, 53 vs. 90 mL/min/1.73 m2, respectively; 0.01 < p < 0.03). The reductions in the median eGFR of both the HB group and controls before and at 36 months after LT were 49 and 41%, respectively. At 36 months after LT, there was a trend for partial recovery of the eGFR in the controls but not in the HB group. Children who underwent LT for unresectable HB had renal dysfunction before transplantation that persisted for 36 months after LT.     

Optimizing vector application for gene transfer into human hepatoblastoma cells

Gene targeting is currently of distinct interest as an innovative additive treatment option in various malignancies. Its role in pediatric liver tumors has not yet been evaluated thoroughly. For the first time the authors systematically analyzed both lipid-based transfection as well as transduction with adenovirus vectors (Ad) and Sendai virus vectors (SeVV) in order to optimize gene transfer into hepatoblastoma (HB) cells. Two HB cell lines were infected with Ad or SeVV coding for green fluorescent protein (Ad-GFP, SeVV-GFP); transduction efficiencies and apoptosis were assessed using flow cytometry. Furthermore, lipofection of HB cell lines with plasmid-constructs comprising liver-specific promoters was performed using Lipofectamine™ 2000 and FuGENE 6™; lipofection efficiency was monitored by flow cytometry, microscopy, and luciferase activity. The Ad-GFP showed higher transduction rates (61–86%) than the SeVV-GFP (4–24%) depending on the HB cell line used. Infections with first generation SeVV vectors (SeVV-GFP) led to increased target cell apoptosis (7–43%) compared to Ad-GFP (4–16%). The Lipofectamine™ 2000 revealed a higher transfection efficiency than the FuGENE 6™ for both HB cell lines tested. The liver-specific promoters were found to be differently active in the HB cell lines. This study delineates recombinant adenovirus vectors as a promising tool for gene transduction in the HB cells. Furthermore, enhanced activity of the liver-specific promoters in HUH6 cells compared to HepT1 cells supports the observation of varying biological behavior in histologically differing HB tissues.S. W. Warmann and S. Armeanu shared equally in the authorship of this paper and J. Fuchs and M. Bitzer share the senior authorship.     

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.     

Atypical radical liver resection in hepatoblastoma

Five consecutive patients (age at presentation 2 1/2–30 months) with hepatoblastoma during a 4-year period are reported. The youngest died due to uncontrolled spontaneous hepatic bleeding prior to any treatment. After considerable tumor shrinkage was achieved by preoperative combined chemotherapy (doxorubicin and cisplatinum), an atypical liver resection with ultrasound knife equipment (USK) was successfully carried out in four patients, all of whom were discharged from the pediatric surgical department free of symptoms on 4th to 10th postoperative day. No recurrences and no tumor metastases occurred following the completion of postoperative chemotherapy. Atypical liver resection with USK is a safe surgical modality that allows the liver parenchyma to be crushed while leaving the bile ducts and vessels intact. These structures can be identified and divided separately. Complete tumor removal from the parenchyma can be performed radically regardless of the surgical resectability as defined by the anatomic borders of the liver segments.     

缺氧诱导因子及其相关蛋白在肝母细胞瘤中的表达

目的 探讨缺氧诱导因子及其相关蛋白在肝母细胞瘤(hepatoblastoma,HB)中表达情况及其作用.方法 选择1998年至2009年入住我院并接受手术的肝母细胞瘤患儿及胆道闭锁患儿各30例,分为三组:肝母细胞瘤肿瘤组织、距肿瘤组织边缘5 cm以外的正常肝脏组织以及胆道闭锁活检肝组织,肿瘤组中以PRETEXT分期系统,将肿瘤组分为低分组(Ⅰ组+Ⅱ组,10例)和高分组(Ⅲ组+Ⅳ组,20例).采用免疫组织化学染色方法检测HIF-1α、HIF-2α、VEGF、GLUT-1、TGF-α在上述标本中的表达情况,并且比较各组的表达情况差异.结果 5种蛋白的阳性表达均主要表现为细胞质内棕黄色颗粒.肿瘤组HIF-1α、HIF-2a、VEGF、GLUT-1、TGF-a表达明显高于其他两组(P<0.01).肿瘤高分组中HIF-1α及TGF-α的表达水平高于低分组(P<0.05),而HIF-2α、VEGF、GLUT-1的表达两者无显著差别.结论 缺氧诱导因子及其相关蛋白在肝母细胞瘤中的表达均有增加,提示HIF可能在肝母细胞瘤的发生发展中起着重要作用,其中HIF-1α还可能是潜在的预后判断指标之一.