High-dose chemotherapy in children with metastatic hepatoblastoma

BACKGROUND: Despite the advent of effective chemotherapy,a poor prognosis has been reported for patients with metastatic hepatoblastoma. To improve this prognosis, we conducted high-dose chemotherapy with autologous bone marrow rescue in patients with metastatic hepatoblastoma. METHODS AND RESULTS: Three patients were treated with high-dose chemotherapy. In patient 1, high-dose chemotherapy was given after the patient's first pulmonary relapse.Additional pulmonary metastases, which developed more than 6 months after high-dose chemotherapy, were treated by multiple thoracotomy without additional chemotherapy. Patient 2 presented additional pulmonary metastases soon after the end of the first thoracotomy and high-dose chemotherapy. Because of a decreased serum alpha-fetoprotein level after re-excision of the pulmonary metastases, a second round of high-dose chemotherapy was performed. In patient 3, multiple pulmonary metasteses responded to preoperative chemotherapy and disappeared according to the chest computed tomography. Intensive treatment with a high-dose chemotherapeutic regimen was performed at the end of postoperative chemotherapy. All three patients are alive and well, more than 6 years after receiving their diagnosis. CONCLUSION: The role of high-dose chemotherapy in treatment of metastatic hepatoblastoma could not be clarified,because of the small number of patients. However, the better outcome of our patients indicates that multimodal therapy, including high-dose chemotherapy, may improve the outcome of the patients with metastatic hepatoblastoma.     

High survival rates after liver transplantation for hepatoblastoma and hepatocellular carcinoma

Kosola S, Lauronen J, Sairanen H, Heikinheimo M, Jalanko H, Pakarinen M. High survival rates after liver transplantation for hepatoblastoma and hepatocellular carcinoma.
Pediatr Transplantation 2010: 14:646–650. © 2010 John Wiley & Sons A/S. Abstract: Unresectable malignant liver tumors may be treated by LTx. We evaluated the results of LTx for HB and HCC. All patients transplanted for HB or HCC between 1990 and 2007 were included. Effects of histologic tumor type, primary tumor resection, disease staging, and serum AFP levels at diagnosis and at transplantation on disease recurrence and survival were evaluated. Twelve patients with median age of five (range, 2–16) were transplanted and followed for a median of 11 (2–18) yr. Six patients had HB and six had HCC. At diagnosis, eight patients were staged as PRETEXT III and four patients as PRETEXT IV. Two patients had pulmonary metastases. All patients received neoadjuvant chemotherapy. Median time from diagnosis to LTx was seven (2–133) months. At LTx, none of the patients had radiological evidence of extrahepatic disease, and the median AFP level was 85 (6–15 180) μg/L. No routine chemotherapy after LTx was used.The overall one‐, five‐, and 10‐yr cumulative survival rates were 100%, 80%, and 67%, respectively. Survival was comparable between the two tumor types (4/6 for both). Two deaths occurred secondary to tumor recurrence, one of each tumor type. Both of these patients had an AFP response of <99%. Six of eight patients with primary LTx survived, when compared to two of four transplanted after primary resection. PRETEXT tumor staging had no effect on survival. LTx even without post‐transplantation chemotherapy is an effective treatment option for unresectable HB and HCC with comparable survival. Incomplete AFP response to chemotherapy and primary tumor resection were associated with decreased survival.     

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.     

Prognostic factors for event‐free survival in liver transplantation for hepatoblastoma: A single‐center experience

Hepatoblastoma (HB) is the most common malignant liver tumor in children. Twenty percent of the cases may remain unresectable after neoadjuvant chemotherapy and, for these patients, liver transplant (LT) is an accepted therapeutic option. To analyze the risk factors to event‐free survival (EFS) that influence the clinical outcome of patients with HB receiving LT, we retrospectively analyzed 21 patients with HB who underwent LT between January 1, 2005, and May 1, 2018. Overall survival (OS) was 90%. The univariate analysis shows that the AFP level at the time of LT was associated with a higher risk of EFS. With a ROC curve analysis, we established a cutoff point value of AFP levels at 16 000 ng/dL, with a sensitivity of 71.43% and a specificity of 85.71%. Multivariate analysis showed that patients with higher values of pretransplant AFP (>16 000 ng/dL) had a significantly higher risk of EFS than those transplanted with lower levels (HR: 10.180; 95% CI: 1.54‐66.97; P = .02). Efforts should be made to improve the selection of candidates for LT for unresectable HB, aiming at a better definition of chemoresistance as a risk factor of poor outcomes.     

Sorafenib and bevacizumab for recurrent metastatic hepatoblastoma: Stable radiographic disease with decreased AFP

We report the use of sorafenib and bevacizumab in combination for a patient with recurrent metastatic hepatoblastoma (HB). This combination demonstrated activity against our patient's refractory HB that had been extensively treated with multiple prior chemotherapeutic regimens. The patient had stabilization of radiographic disease coupled with an 83% decrease in his alpha‐fetoprotein level. Given the response in this setting and the paucity of other available options, consideration could be given to using this combination as therapy in patients with recurrent HB who have failed more traditional agents. Pediatr Blood Cancer 2012; 59: 939–940. © 2012 Wiley Periodicals, Inc.     

Cisplatin-resistant metastatic hepatoblastoma: Complete response to carboplatin,etoposide, and liver transplantation

A child with stage 4 hepatoblastoma failed to respond to treatment with cisplatin and adriamycin. She then showed a response to carboplatin with complete clearing of pulmonary metastases. Bilobar liver disease persisted, although significantly reduced in size. A liver transplant was subsequently performed and she remains in complete remission 36 months later. After the first course of carboplatin, there was a dramatic rise in alpha-feto protein which then fell exponentially. Carboplatin warrants further study in hepatoblastoma. © 1993 Wiley-Liss, Inc.     

Results of surgical resections with positive margins for children with hepatoblastoma: Case series from a single Asian center

The influence of margin status on the survival of patients with hepatoblastoma (HB) remains controversial. Here, we report long‐term follow‐up outcomes of 26 patients with HB who underwent hepatectomy with positive microscopic margins. Although these patients had microscopic residuals, the 5‐year overall survival and event‐free survival rates of those who had no metastases or macrovascular involvement (MVI) were 86.7% and 80.8%, respectively. This may support the hypothesis that patients with HB who undergo hepatectomy with positive microscopic residuals but without MVI or metastases can also achieve satisfactory survival rate. Further studies in this field are required.     

Primary chemotherapeutic management of unresectable and metastatic hepatoblastoma in children: Report of four cases

Four children presenting with unresectable hepatoblastomas and one with metastatic disease are reported. Following initial biopsy all were treated with chemotherapy which included Adriamycin. Three of the four children showed a significant reduction in tumor size, and in two, delayed resection of the primary lesion was possible. Chemotherapy including Adriamycin represents effective initial cytoreductive therapy for childhood hepatoblastoma, thereby reducing the morbidity and mortality associated with the extensive hepatic resection usually required for an untreated lesion.     

Relapsed hepatoblastoma

Successful treatment of recurrent hepatoblastoma (HB) relies largely on surgical resection. When tumors are responsive, chemotherapy can be used to render patients resectable. Various chemotherapeutic regimens studied in small numbers of patients on phase I/II trials have shown few responses. The best available data indicate that doxorubicin, if not given during intial treatment, and irinotecan are the most active agents in recurrent HB. Stem cell transplantation and radiation therapy have been reported in several patients with unclear successes. Advances in therapy for relapsed patients require concentrating enrollment in one or two phase I/II trials utilizing agents with promising preclinical data. Pediatr Blood Cancer 2012; 59: 813–817. © 2012 Wiley Periodicals, Inc.     

Chemotherapeutic approaches for newly diagnosed hepatoblastoma: Past, present, and future strategies

Surgical resection is the foundation of therapy in hepatoblastoma (HB), yet most patients have unresectable tumors at diagnosis 1 . Patients with resectable tumors have event‐free survival (EFS) of 80–90% and can be cured with cisplatin, 5‐fluorouracil, and vincristine. Patients whose tumors are unresectable but without overt metastases at diagnosis have EFS of 60–70%, and many can be rendered resectable without doxorubicin. Children with metastatic disease have fared poorly with 20–50% EFS 1 - 3 , and new approaches for these patients remain desperately needed. Dose intensification of cisplatin and doxorubicin appears beneficial in high‐risk patients. Future treatment strategies, which may be useful, include increasing intensity and/or duration of therapy, developing a maintenance regimen (oral irinotecan), using liver transplantation more often for patients to undergo complete resection, and identifying and incorporating novel agents. A better understanding of the biologic and pathologic factors is critical for predicting tumor behavior and developing more logical risk‐based treatments. Pediatr Blood Cancer 2012; 59: 809–812. © 2012 Wiley Periodicals, Inc.     

Long‐term outcomes of liver transplantation for hepatoblastoma: A single‐center 14‐year experience

HB is the most common primary liver tumor in children. Complete tumor excision, either by partial resection or by total hepatectomy and liver transplantation, in combination with chemotherapy provides the best chance for cure. We performed a retrospective analysis of patients who underwent liver transplantation for HB and herein present our 14‐year single‐institution experience. Twenty‐five patients underwent liver transplantation for HB at a median age of 26 months (IQR: 15‐44). Graft survival was 96%, 87%, and 80% at 1, 3, and 5 years, respectively. There were four patient deaths, three of them due to disease recurrence within the first year post‐transplant. Ten‐year overall survival was 84%. Three recipients initially presented with pulmonary metastases and underwent resection of metastatic disease, of which two are alive at 3.9 years. Of three patients who underwent salvage transplants, two are alive at 1.5 years after transplant. Non‐survivors were associated with lower median alpha fetoprotein value at presentation compared to survivors (21 707 vs 343 214; P = .04). In conclusion, the overall long‐term outcome of primary liver transplantation for HB is excellent. Tumor recurrence was the highest contributor to mortality. Even patients with completely treated pulmonary metastases prior to transplant demonstrated a favorable survival.     

Sialoblastoma and hepatoblastoma in a newborn infant

We report a case of a newborn infant who had simultaneous sialoblastoma and hepatoblastoma tumours at birth. The diagnoses were made on post mortem examination. Both of these are rare tumours in the neonatal period. Pediatr Blood Cancer 2009;52:883–885. © 2009 Wiley‐Liss, Inc.     

儿童肝母细胞瘤研究现状

肝母细胞瘤(hepatoblastoma,HB)是儿童期最常见的肝脏恶性肿瘤。HB起病隐匿,诊断和治疗都有一定的困难。近年来HB的发病率有上升趋势,对HB的研究也逐渐深入。文章就HB的病因、病理分型、临床分期、预后因素及治疗原则等研究结果作一综述。     

小儿亲体部分肝移植治疗肝母细胞瘤(附1例报告)

目的探讨小儿部分亲体肝移植治疗肝母细胞瘤的临床经验。方法对1例患肝母细胞瘤的4岁男童实施母亲供肝,左外肝叶亲体部分肝移植。结果供体于术后7d痊愈出院,受体于术后22d出院,无并发症。随访24个月,小儿生长发育良好,正常上学,无特殊不适。结论实施小儿亲体部分肝移植扩大了供肝来源,临床疗效好,可作为治疗肝母细胞瘤等小儿终末期肝病的有效治疗方法。     

The epidemiology of hepatoblastoma

Few causes of hepatoblastoma have been conclusively identified, mainly due to the extreme rarity of the disease. Inherited conditions including Familial Adenomatous Polyposis and Beckwith–Wiedemann Syndrome dramatically raise risk of hepatoblastoma but account for few cases overall. A small number of case–control studies investigating risk factors for sporadic hepatoblastoma have been conducted to date. Although most of these studies feature fewer than 200 cases, several clues have emerged. Most notably there is a roughly 20‐fold increased risk of hepatoblastoma among children with very low birth weight (<1,500 g) and a doubling of risk among those with moderately low birth weight (1,500–2,500 g). A modicum of evidence points to a possible role of parental tobacco use prior to or during pregnancy in the causation of hepatoblastoma as well. Pediatr Blood Cancer 2012; 59: 776–779. © 2012 Wiley Periodicals, Inc.