This research investigated the impact of Ganoderma lucidum polysaccharides(GLP) on hepatoblastoma HepG2 and Huh6 cell models, as well as KM mouse model with in situ transplanted tumors, so as to provide a theoretical basis for the clinical application of GLP. Cell viability was assessed through the CCK-8 assay, whereas cell proliferation was evaluated by using the BeyoClick~(TM)EdU-488 test. Cell apoptosis was visualized via Hochest 33258 staining, and autophagy was detected through Mrfp-GFP-LC3 dual fluorescence staining. An in situ tumor transplantation model was created by using HepG2 cells in mice, and mice were treated with normal saline and GLP of 100, 200, and 300 mg·kg~(-1) for tumor count calculation and size assessment. Hematoxylin-eosin(HE) staining was used to observe pathological changes in tumor tissue and vital organs(liver, kidney, lung, spleen, and heart). Western blot analysis was conducted to measure the protein expressions of tumor protein P53(P53), B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), cleaved-caspase-3, Beclin-1, autophagy related protein-5(Atg-5), microtubule-associated protein-light chain-3Ⅰ(LC3Ⅰ)/LC3Ⅱ, autophagy adapter protein 62(P62), protein kinase B(Akt), p-Akt, mammalian target of rapamycin(mTOR), and p-mTOR. The in vitro experiment revealed that compared with the control group, after GLP treatment, tumor cell viability decreased significantly; apoptosis rate increased in a dose-dependent manner, and autophagic flux was inhibited. The in vivo experiments showed that compared with the model group, mice treated with GLP exhibited significantly fewer and smaller tumors. Western blot results showed that compared with the control group or model group, levels of P53, Bax, cleaved-caspase-3, Beclin-1, Atg-5, and LC3-Ⅱ/LC3-Ⅰ were significantly increased after GLP treatment, and the levels of Bcl-2, P62, p-Akt/Akt, and p-mTOR/mTOR were significantly decreased. These outcomes suggest that GLP promotes apoptosis and autophagy in hepatoblastoma cells by regulating the Akt/mTOR pathway.
Animals ; Humans ; Autophagy/drug effects* ; Reishi/chemistry* ; Mice ; Apoptosis/drug effects* ; TOR Serine-Threonine Kinases/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Liver Neoplasms/genetics* ; Hepatoblastoma/genetics* ; Polysaccharides/pharmacology* ; Cell Line, Tumor ; Signal Transduction/drug effects* ; Male ; Cell Proliferation/drug effects* ; Hep G2 Cells

OBJECTIVES: To assess the preliminary efficacy and safety of a dose-intensified C5VD regimen (cisplatin, 5-fluorouracil, vincristine, and doxorubicin) in children with locally advanced hepatoblastoma. METHODS: This prospective study enrolled 24 children with newly diagnosed, locally advanced hepatoblastoma who received the dose-intensified C5VD regimen at Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, and Shanghai Children's Hospital between January 2020 and December 2023. Clinical characteristics, treatment outcomes, and chemotherapy-related toxicities were analyzed. RESULTS: Of the 24 patients, 13 were male and 11 were female, with a median age at diagnosis of 18.7 months (range: 3.5-79.4 months). All patients achieved complete macroscopic resection of hepatic lesions without liver transplantation. Serum alpha-fetoprotein levels decreased significantly after two chemotherapy cycles. During a median follow-up of 38.4 months (range: 15.8-50.7 months), all patients maintained continuous complete remission, with 3-year event-free survival and overall survival rates of 100%. Across 144 chemotherapy cycles, the incidence rates of grade 3-4 neutropenia, thrombocytopenia, and infections were 97%, 77%, and 71%, respectively; no treatment-related deaths occurred. Notably, 5 patients (21%) developed Brock grade ≥3 hearing loss, of whom 1 required a hearing aid. CONCLUSIONS The dose-intensified C5VD regimen demonstrates significant efficacy with an overall favorable safety profile in the treatment of newly diagnosed, locally advanced pediatric hepatoblastoma. Grade 3-4 myelosuppression and infection are the predominant toxicities. However, high‑dose cisplatin-induced ototoxicity remains a concern, highlighting the need for improved otoprotective strategies.
Humans ; Hepatoblastoma/pathology* ; Male ; Female ; Infant ; Liver Neoplasms/pathology* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Child, Preschool ; Prospective Studies ; Doxorubicin/adverse effects* ; Child ; Cisplatin/adverse effects* ; Vincristine/adverse effects* ; Fluorouracil/adverse effects*

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

Carcinogenesis ; Cell Transformation, Neoplastic ; Hepatoblastoma ; Humans ; Liver ; Liver Neoplasms ; Organoids ; YAP-Signaling Proteins

Aged ; Female ; Hepatoblastoma ; Humans ; Liver Neoplasms/surgery* ; Tomography, X-Ray Computed

Hepatoblastoma (HB) is a rare pediatric malignant tumor of the liver. Most of these tumors arise in the embryo and this is usually discernible in the first 3 years of life; thus, its occurrence in the adult population seems to be unusual. We present this case due to its rarity and its potential to mimic other primary liver tumors in adults such as HCC. To the best of our knowledge with literature review, there are only 40 cases of adult HB reported worldwide. In this paper, we report a case of a 49-year-old female, diagnosed with Chronic Hepatitis B, admitted due to abdominal pain. Physical examination revealed hepatomegaly. Liver function test was unremarkable. AFP was elevated at >50,000ng/mI. Triphasic CT scan revealed a hypodense mass in the right lobe of the liver measuring approximately 11 × 11 × 13cm suggestive of HCC. Subsequently, patient underwent right hepatectomy. Pathological examination, however, demonstrated that the tumor showed a malignant neoplasm with epithelial and mesenchymal components consistent with adult HB, mixed type. Since treatment of adult HB is not yet established, studies have suggested that it is logical to follow the treatment protocol for childhood HB. Hence, this patient underwent chemotherapy with Cisplatin, Vincristine and 5-Fluorouracil. The low incidence of HB in adults presents a diagnostic challenge, requiring a high index of suspicion and a thorough evaluation. Since prognosis could be improved with early detection and treatment, it is important for clinicians not to overlook HB.
Hepatoblastoma ; Hepatomegaly

OBJECTIVE: To summarize and analyze the treatment process, long-term efficacy and clinical economics of children's hepatoblastoma (HB) in multi-disciplinary team (MDT) mode, so as to provide basis for the rational choice of diagnosis and treatment. METHODS: From January 2014 to February 2019, 13 cases of hepatoblastoma in children who completed the whole treatment course in the Pediatric Hematology Tumor Ward of Peking University First Hospital were collected and analyzed, and were followed up until June 30, 2020. There were 9 males and 4 females who were diagnosed and treated according to the MDT process in the hospital. The median age was 16 months (2-54 months), 69.23% (9/13) were under 2 years old. The characteristics, diagnosis and treatment process and treatment effect of the cases were summarized, and the cost of clinical treatment was analyzed. RESULTS: According to the pretreatment extent of disease(PRETEXT), there were 1, 9 and 3 children with stages Ⅱ, Ⅲ and Ⅳ. 76.92% (10/13) of the patients had the largest tumor diameter > 10 cm. All the patients received preoperative neoadjuvant chemotherapy (8 patients received 4 cycles of chemotherapy, and 6 patients changed the chemotherapy plan), surgical treatment and postoperative chemotherapy, the tumor volume decreased by more than 50% (64%-95%) in 12 cases, except 1 case with no significant increase of alpha fetal protein and multiple lesions.The median length of stay was 87 days (68-214 days), the median cost of stay was 200 000 yuan (115 000-500 000 yuan), the median length of stay was 7 days (5-17 days), the median cost of stay was 20 000 yuan (15 000-60 000 yuan), and the incidence of postoperative complications was 7.69% (1/13). All the patients were followed up for 16-69 months. All the patients survived. CONCLUSION Under the MDT mode, the treatment is seamless connection, the long-term prognosis of children with HB is good, and the total hospitalization cost and time are within the acceptable range. Standard preoperative neoadjuvant chemotherapy can significantly reduce the tumor, improve the resection rate, reduce postoperative complications, reduce the total individual expenditure, shorten the total hospital stay, and further improve the long-term disease-free survival rate.
Child ; Disease-Free Survival ; Female ; Hepatoblastoma/therapy* ; Humans ; Infant ; Liver Neoplasms/therapy* ; Male ; Neoadjuvant Therapy ; 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

Patients with Beckwith-Wiedemann syndrome (BWS) are predisposed to developing embryonal tumors, with hepatoblastoma being the most common type. Our patient showed hemihypertrophy, macroglossia, and paternal uniparental disomy in chromosome 11 and was diagnosed with BWS. When the patient was 9 months old, a 2.5×1.5 cm oval hypoechoic exophytic mass was detected in the inferior tip of his right liver. Preoperative imaging identified it as hepatoblastoma; however, histologic, immunohistochemistry, and electron microscopic findings were compatible with adrenal cortical neoplasm with uncertain malignant potential. The origin of the adrenal tissue seemed to be heterotopic. Here, we describe for the first time an adrenal cortical neoplasm with uncertain malignant potential arising in the heterotopic adrenal cortex located in the liver of a patient with BWS.
Adrenal Cortex ; Adrenal Gland Neoplasms ; Beckwith-Wiedemann Syndrome ; Chromosomes, Human, Pair 11 ; Hepatoblastoma ; Humans ; Immunohistochemistry ; Liver ; Macroglossia ; Uniparental Disomy

Gastric volvulus (GV) is an uncommon pathology, with 10-20% of cases occurring in children, typically before one year of age. It often occurs in people with congenital diaphragmatic hernias, intestinal malrotation, eventration of the diaphragm, paraesophageal hernias, wandering spleens, asplenism, or intra-abdominal adhesions. We report a rare case of chronic GV after left hemihepatectomy for hepatoblastoma in a child. The patient was a 9-year-old boy who complained of upper abdominal pain and postprandial upper abdominal distension for one year. At the age of 4 months, he was diagnosed with hepatoblastoma and had undergone left hemihepatectomy. The upper gastrointestinal contrast study revealed chronic organoaxial gastric volvulus. After a surgical procedure involving adhesiolysis and an anterior wall gastropexy, the patient improved and the symptoms resolved. Although GV is a rare disease, it should be suspected in a patient with a previous abdominal surgical history who is complaining of abdominal distension and pain.
Abdominal Pain ; Child ; Diaphragm ; Gastropexy ; Hepatectomy ; Hepatoblastoma ; Hernia, Hiatal ; Hernias, Diaphragmatic, Congenital ; Humans ; Male ; Pathology ; Rare Diseases ; Stomach Volvulus ; Wandering Spleen