Objective: To investigate the clinical features, survival and prognostic risk factors of children with hepatoblastoma (HB). Methods: Clinical data of 83 children with newly treated HB at the Department of Hematology and Oncology, Children's Hospital, the First Affiliated Hospital of Zhengzhou University from January 2012 to October 2019 were analyzed retrospectively. The sex, age, first clinical manifestations, pretreatment extent of disease (PRETEXT) stages, pathological types, initial alpha-fetoprotein (AFP), treatment methods and treatment outcome of all patients were summarized. The children diagnosed before 2018 were treated with "Wuhan Protocol", and those who diagnosed after 2018 were treated with the "Expert Consensus for Multidisciplinary Management of Hepatoblastoma"(CCCG-HB-2016) protocol. Kaplan-Meier survival analysis was used to calculate the survival rate, Log-Rank test was used in univariate analysis, and the Cox regression model was used in multivariate prognosis analysis. Results: Among 83 cases, there were 51 males and 32 females. The age of onset was 25.2 (9.0, 34.0) months old, and 64 cases (77%) were under 3 years old. The most common first clinical manifestation was abdominal mass in 45 cases (54%). There were 8 cases of PRETEXT stage Ⅰ, 43 cases of stage Ⅱ, 20 cases of stage Ⅲ and 12 cases of stage Ⅳ. During the follow-up period of 40 (17, 63) months, the 1-year overall survival (OS) rate and event-free survival (EFS) rate were (84±4) % and (79±5) %, respectively, and 5-year OS rate and EFS rate were (78±5) % and (76±5) %, respectively. Fifty-five cases were treated with "Wuhan Protocol", and the 5-year OS and EFS rate were (73±6) % and (71±6) %, respectively. Twenty-eight cases were treated with CCCG-HB-2016 protocol, and the 5-year OS and EFS rate were (88±7) % and (82±9) %, respectively. Multivariate COX regression analysis showed that AFP did not turn negative after 3 courses of postoperative chemotherapy (HR=9.228, 95%CI 1.017-83.692) and PRETEXT stage Ⅳ (HR=6.587, 95%CI 1.687-25.723) were independent risk factors affecting the prognosis of children with HB. Conclusions: The "Wuhan Protocol" and CCCG-HB-2016 protocol were effective in the treatment of children with HB. AFP did not turn negative after 3 courses of postoperative chemotherapy and PRETEXT stage Ⅳ were independent risk factors affecting the prognosis of children with HB.
Female ; Hepatoblastoma/drug therapy* ; Humans ; Infant ; Liver Neoplasms ; Male ; Prognosis ; Retrospective Studies ; Treatment Outcome

Hepatic osteodystrophy is frequent complication in patients with chronic liver disease, particularly with chronic cholestasis. We report a male infant with congenital hepatoblastoma, who had osteodystrophy complicated by multiple bone fractures despite adequate supplementation of fat-soluble vitamins including vitamin D. He was born by Caesarean section because of a 7 cm–sized abdominal mass detected by prenatal ultrasonography. The pathologic diagnosis was hepatoblastoma, PRETEXT staging III or IV. Whole body bone scan at the time of diagnosis showed no abnormal uptake. Oral vitamin D3 of 2,000 IU/day was administered with other fat-soluble vitamins. Serum direct bilirubin level gradually increased up to 28.9 mg/dL at postnatal 6 days and was above 5 mg/dL until 110 days of age. Bony changes consistent with rickets became apparent in left proximal humerus since 48 days of age, and multiple bone fractures developed thereafter. With resolving cholestasis by chemotherapy, his bony lesions improved gradually after add-on treatment of bisphosphonate and parenteral administration of vitamin D with calcium. High level of suspicion and prevention of osteodystrophy is needed in patients with hepatoblastoma, especially when cholestasis persists.
Bilirubin ; Calcium ; Cesarean Section ; Cholecalciferol ; Cholestasis ; Diagnosis ; Drug Therapy ; Female ; Fractures, Bone ; Hepatoblastoma ; Humans ; Humerus ; Infant ; Liver Diseases ; Male ; Pregnancy ; Rickets ; Ultrasonography, Prenatal ; Vitamin D ; Vitamins

Spontaneous rupture with internal bleeding of solid tumors has rarely been described at the time of diagnosis or during chemotherapy. This rare event must be regarded as a life threatening condition. In these emergency situations, control of hemorrhage, which is life-saving, can be achieved by transcatheter arterial embolization (TAE) and/or surgical resection. This report describes two infants presenting with acute hemorrhagic shock due to spontaneous tumor rupture of hepatoblastoma and neuroblastoma during chemotherapy. TAE successfully arrested the tumor bleeding and a visibly reduced the tumor size in both children. Spontaneous rupture of solid tumors occur infrequently in children, but is a life threatening situation. Careful monitoring for the occurrence of this rare event especially in very young children presenting with a large tumor mass.
Child ; Diagnosis ; Drug Therapy ; Emergencies ; Hemorrhage ; Hepatoblastoma ; Humans ; Infant ; Neuroblastoma ; Rupture ; Rupture, Spontaneous ; Shock, Hemorrhagic

OBJECTIVETo summarize the experience of the chemotherapy regimen cisplatin + fluorouracil + vincristine (C5V) for hepatoblastoma, and analyze the factors associated the outcome.

METHODA retrospective analysis was conducted for the outcome of hepatoblastoma. Sixty-three patients who received the regimen of C5V as the first choice of chemotherapy were reviewed, including 37 males and 26 females. The age at diagnosis ranged from 2 days after birth to 124 months, median 15 months. Four patients with stage I, 16 patients with stage II, 28 patients with stage III, 15 patients with stage IV disease were enrolled in the study. Nine patients had primary tumor resection while the remain by 54 received neoadjuvant chemotherapy. The median follow-up time was 30 months.

RESULTForty patients had delayed surgery, including 35 patients with regimen C5V alone, the others were treated with regimen C5V and cisplatin + adriamycin (CITA). The mean time of neojuvant chemotherapy was (3.4 ± 1.7) cycles. The mean time of chemotherapy after surgery was (5.3 ± 2.0) cycles. In 12 cases the (24.5%) tumor recurred after surgery. The margin of resection less than 0.5 cm , vascular invasion, stage III or IV disease were all the high risks of relapse (P = 0.049,0.001,0.022, respectively). Two-year overall survival (OS) and 5-year OS of the study was 61.1% and 58.7%, respectively. The 2-year OS and 5-year OS of stage I to III were 75.0% and 75.0%, 100.0% and 100.0%, 65.8% and 61.4%. The 1-year OS and 3-year OS of stage IV was 20.0%, 13.3%, respectively. Univariate analysis showed that age at diagnosis less than 60 months, vascular invasion, thrombocythemia at diagnosis, stage III or IV, tumor resection was the prognostic factor (P = 0.019, <0.001,0.011, <0.001, respectively). Multivariate analysis showed that tumor resection and age at diagnosis less than 60 months were both the prognostic factor (P < 0.001, 0.004, respectively ).

CONCLUSIONThe regimen of C5V is useful for hepatoblastoma. Tumor resection is the key factor of treatment. Prognostic factor is composed of age, stage, and clinical sign at diagnosis.

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Child ; Child, Preschool ; Cisplatin ; administration & dosage ; Doxorubicin ; administration & dosage ; Female ; Fluorouracil ; administration & dosage ; Hepatoblastoma ; drug therapy ; Humans ; Infant ; Infant, Newborn ; Liver Neoplasms ; drug therapy ; Male ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Retrospective Studies ; Vincristine ; administration & dosage

Hepatoblastoma usually occurs in children under the age of 2 years, with very few cases reported in adults. We experienced a case of adult hepatoblastoma in a 36-year-old female with chronic hepatitis B . She had experienced sudden onset abdominal pain. Her serum alpha-fetoprotein level was markedly elevated, and abdominal CT showed a 9-cm mass with internal hemorrhage in the right hepatic lobe with hemoperitoneum, so an emergency hepatic central bisectionectomy was performed. The initial histologic examination revealed that the mass mimicked combined hepatocellular carcinoma and cholangiocarcinoma with spindle-cell metaplasia of the cholangiocarcinoma element. Follow-up abdominal CT performed 3 months later showed a 5.5-cm metastatic mass in the left subphrenic area. Laparoscopic splenectomy with mass excision was performed, and hepatoblastoma was confirmed histologically. A histologic re-examination of previously obtained surgical specimens also confirmed the presence of hepatoblastoma. Metastatic hepatoblastoma was found at multiple sites of the abdomen during follow-up, and so chemotherapy with cisplatin, 5-fluorouracil (5-FU), and vincristine was applied, followed by carboplatin and doxorubicin . Despite surgery and postoperative chemotherapy, she died 12 months after symptom onset.
Adult ; Carcinoma, Hepatocellular/pathology ; Cholangiocarcinoma/pathology ; Cisplatin/therapeutic use ; Diagnostic Errors ; Doxorubicin/therapeutic use ; Drug Therapy, Combination ; Female ; Fluorouracil/therapeutic use ; Hepatitis B, Chronic/complications/diagnosis ; Hepatoblastoma/drug therapy/*pathology/radiography ; Humans ; Liver Neoplasms/drug therapy/*pathology/radiography ; Tomography, X-Ray Computed ; Vincristine/therapeutic use

Hepatoblastoma, the most common primary liver tumor of early childhood, is a rare neoplasm, accounting for 0.8-2.0% of all pediatric cancers. The etiology is unknown. The most common method of testing for hepatoblastoma is alpha-fetoprotein (AFP). AFP is used as a biomarker for presence of residual liver tumor, therefore indicator of the successful treatment. Multimodal therapy is composed of chemotherapy and surgical intervention. In general, the cure of hepatoblastoma in children depends on complete resection of the primary tumor. While > or =90% of patients who undergone primary complete resection of their tumors can be cured, patients with unresectable or metastatic tumors show survival rate of < or =65%. Liver transplantation (LT) is a feasible treatment option for carefully selected patients who are free of extrahepatic disease prior to LT. The still dismal outcome of multifocal disseminated tumors warrants the investigation of new cytotoxic drug and substances against specific molecular targets.
alpha-Fetoproteins ; Child ; Drug Therapy ; Hepatoblastoma ; Humans ; Liver ; Liver Transplantation ; Survival Rate

AIM: To investigate the cytotoxic effects of the six protoberberine alkaloids (PAs) from Rhizoma Coptidis on HepG2 cells. METHOD: A systematic screening was conducted to investigate the dynamic response of HepG2 cells to the PAs using the impedance-based xCELLigence system. Cisplatin was selected as the positive control. The real time, concentration-response curves and the 50% inhibitory concentrations (IC50) were acquired to evaluate the anticancer activity of the PAs. RESULTS: All of the six PAs inhibited cell growth and induce death in HepG2 cells in a time- and concentration-dependent manner. The IC50 values of cisplatin, berberine, columbamine, coptisine, epiberberine, jatrorrhizine, and palmatine were 5.13, 42.33, 226.54, 36.90, 302.72, 383.54, and 456.96 μg·mL(-1), respectively. The results obtained using the xCELLigence system corresponded well with those of the conventional methods. CONCLUSION The xCELLigence system is a reliable and efficient tool for real-time screening of the cytotoxic effect of compounds in cell-based in vitro assays. Coptisine and berberine, with methylenedioxy group at C2 and C3 on the phenyl ring showed stronger effect.than the other four PAs. However, compared with cisplatin, the six PAs didn't show obvious cytotoxic effect on HepG2 cells. These results provided some useful data for the evaluation of the anticancer compounds, and the clinical application of traditional Chinese medicine.
Antineoplastic Agents, Phytogenic ; pharmacology ; therapeutic use ; Berberine ; analogs & derivatives ; pharmacology ; therapeutic use ; Berberine Alkaloids ; pharmacology ; therapeutic use ; Cell Death ; drug effects ; Cisplatin ; pharmacology ; therapeutic use ; Coptis ; chemistry ; Drug Evaluation, Preclinical ; methods ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Electric Impedance ; Hep G2 Cells ; Hepatoblastoma ; drug therapy ; physiopathology ; Humans ; Inhibitory Concentration 50 ; Liver Neoplasms ; drug therapy ; physiopathology ; Phytotherapy ; Rhizome ; chemistry

Antineoplastic Agents, Phytogenic ; therapeutic use ; Camptothecin ; adverse effects ; analogs & derivatives ; therapeutic use ; Child ; Child, Preschool ; Female ; Hepatoblastoma ; drug therapy ; Humans ; Liver Neoplasms ; drug therapy ; Male ; Neoplasm Recurrence, Local ; drug therapy

OBJECTIVETo evaluate the efficacy and safety of the ICE regimen (iphosphamide + carboplatin + etoposide) used in treating children with hepatoblastoma in the Shanghai Children's Medical Center.

METHODSFrom June 2000 to June 2008, 14 children with newly diagnosed hepatoblastoma (7 males and 7 females) were enrolled. Their median age on diagnosis was 1.33 years (range: 0.25-8.25 years). Six patients had stage I disease, 1 had stage II, 5 had stage III, and 2 had stage IV diseases. Thirteen children had markedly increased serum AFP level, and 1 had normal serum AFP level. Multidisciplinary co-operation treatment was performed. Eight patients had primary surgery while 3 patients had pre-operation chemotherapy before surgery. ICE chemotherapy regimen was used. Totally, 73 courses of chemotherapy were administered for the 14 children and 25 out of the 73 courses were performed before operation.

RESULTSTwelve patients responded to the treatment (85.7%) and 2 failed. Ten patients (71.4%) achieved complete remission after treatment, and two had partial remission. By July 31st, 2008, 9 patients survived without any event, with a median follow-up duration of 35 months (range: 16-96 months). The 5-year overall survival rate was 70.71+/-12.37%, and the 5-year event-free survival rate was 64.29+/-12.81%. One patient had disease relapse and two patients were lost to follow-up after they achieved partial remission.

CONCLUSIONSThe ICE regimen combined with operation is effective and safe in treating children with hepatoblastoma.

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carboplatin ; administration & dosage ; Child ; Child, Preschool ; Etoposide ; administration & dosage ; Female ; Hepatoblastoma ; drug therapy ; Humans ; Ifosfamide ; administration & dosage ; Infant ; Liver Neoplasms ; drug therapy ; Male

Hepatoblastoma is the most common primary malignant hepatic tumor in infancy and childhood. But congenital hepatoblastomas are extremely rare and show distinctive, but important features when compared with tumors diagnosed in children beyond the neonatal age. They have different clinical presentations, higher incidence of pure fetal histology, significant risk for systemic metastasis, and worse outcome. The treatment of congenital hepatoblastoma should be the same as in older children, i.e., primary chemotherapy with delayed resection. We report a case of congenital hepatoblastoma in a 29-day-old boy who was known to have a well-defined ovoid hypoechoic mass at liver demonstrated by fetal sonography.
Child ; Drug Therapy ; Hepatoblastoma* ; Humans ; Incidence ; Liver ; Male ; Neoplasm Metastasis