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*

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

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

Fucoidan is one of the main bioactive components of polysaccharides. The current study was focused on the anti-tumor effects of fucoidan on human heptoma cell line HepG2 and the possible mechanisms. Fucoidan treatment resulted in cell cycle arrest and apoptosis of HepG2 cells in a dose-dependent manner detected by MTT assay, flow cytometry and fluorescent microscopy. The results of flow cytometric analysis revealed that fucoidan induced G2/M arrest in the cell cycle progression. Hoechst 33258 and Annexin V/PI staining results showed that the apoptotic cell number was increased, which was associated with a dose-dependent up-regulation of Bax and down-regulation of Bcl-2 and p-Stat3. In parallel, the up-regulation of p53 and the increase in reactive oxygen species were also observed, which may play important roles in the inhibition of HepG2 growth by fucoidan. In the meantime, Cyclin B1 and CDK1 were down-regulated by fucoidan treatment. Down-regulation of p-Stat3 by fucoidan resulted in apoptosis and an increase in ROS in response to fucoidan exposure. We therefore concluded that fucoidan induces apoptosis through the down-regulation of p-Stat3. These results suggest that fucoidan may be used as a novel anti-cancer agent for hepatocarcinoma.
Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Blotting, Western ; CDC2 Protein Kinase ; genetics ; metabolism ; Cyclin B1 ; genetics ; metabolism ; Dose-Response Relationship, Drug ; Down-Regulation ; drug effects ; Flow Cytometry ; G2 Phase Cell Cycle Checkpoints ; genetics ; Gene Expression Regulation, Neoplastic ; drug effects ; Hep G2 Cells ; Hepatoblastoma ; genetics ; metabolism ; pathology ; Humans ; Liver Neoplasms ; genetics ; metabolism ; pathology ; Microscopy, Fluorescence ; Polysaccharides ; pharmacology ; Proto-Oncogene Proteins c-bcl-2 ; genetics ; metabolism ; Reactive Oxygen Species ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; STAT3 Transcription Factor ; genetics ; metabolism ; Tumor Suppressor Protein p53 ; genetics ; metabolism ; bcl-2-Associated X Protein ; genetics ; metabolism

OBJECTIVETo explore the expression and diagnostic significance of glypican-3 (GPC3) in hepatoblastoma.

METHODSFive tissue microarray paraffin blocks were constructed to include 54 cases of hepatoblastoma. The tumor tissue samples were obtained from 3 surgical biopsies, 33 needle biopsies, 5 stage I resection tumors, and 13 stage II resection tumors after transcatheter arterial chemoembolization. Ten samples of non-neoplastic hepatic tissue adjacent to tumor were used as control. Immunohistochemical staining of GPC3 (clone 1G12) was performed. Among the 54 cases of hepatoblastoma, 22 cases were fetal subtype, 24 cases were mixed fetal and embryonal subtype and 8 cases were mixed epithelial and mesenchymal type.

RESULTSGPC3 was positive in fetal epithelial cells (54/54, 100%), but negative or weakly positive in embryonic epithelial cells in all cases of hepatoblastoma. Undifferentiated small cells and all mesenchymal components were negative for the expression. Non-neoplastic hepatocytes adjacent to tumor were negative for GPC3 expression (0/10) .

CONCLUSIONSFetal epithelial components of hepatoblastoma express GPC3 protein detectable by immunohistochemistry. Normal hepatocytes after birth, small cell undifferentiated and embryonic epithelial components of hepatoblastoma do not or weakly express GPC3 protein. Therefore, GPC3 immunohistochemistry offers a valuable aid to the diagnosis of hepatoblastoma in infants and children.

Child ; Child, Preschool ; Diagnosis, Differential ; Epithelial Cells ; metabolism ; Female ; Glypicans ; metabolism ; Hepatoblastoma ; diagnosis ; metabolism ; pathology ; Humans ; Immunohistochemistry ; Infant ; Infant, Newborn ; Liver Neoplasms ; diagnosis ; metabolism ; pathology ; Male

BACKGROUNDHepatoblastoma (HB) is a rare childhood tumor. We investigated the effect of intraoperative management of the intrahepatic major vessels in children with HB.

METHODSBetween April 2005 and August 2012, surgical resection was performed on 50 children with hepatoblastoma. These children were divided into a vessel-ligation group (n = 20) and a vessel-repair group (n = 30). In the vessel-ligation group, the intrahepatic major vessels were ligated and removed together with the tumor and the affected liver lobe/liver parenchyma. In the vessel-repair group, the affected intrahepatic major vessels were dissected and preserved as much as possible and the normal liver lobe/liver parenchyma and blood supply from these vessels were also preserved. The outcomes were analyzed by postoperative follow-up.

RESULTSIn the vessel-ligation group, two patients gave up surgery, six patients underwent palliative resection, and 12 patients underwent en bloc resection; four patients died of liver failure and eight patients fully recovered and were discharged. In the vessel-repair group, all 30 patients underwent en bloc resection and were discharged after satisfactory healing. After a follow-up time of 5 - 36 months (median: 20 months), two patient in the vessel-ligation group survived and 22 patients in the vessel-repair group survived.

CONCLUSIONSPatients with HB can be successfully treated by tumor resection with vascular repair. This method prevents postoperative liver failure, ensures patient safety during the perioperative period, and allows for early chemotherapy.

Child ; Child, Preschool ; Female ; Follow-Up Studies ; Hepatoblastoma ; blood supply ; pathology ; surgery ; Humans ; Infant ; Liver Neoplasms ; blood supply ; pathology ; surgery ; Male ; Neoplasm Staging

OBJECTIVETo study the expression of glucose-regulated protin 78 (GRP78) and glucose-regulated protin 94 (GRP94) in the liver tissues from children with hepatoblastoma (HB) and to investigate the possible clinicopathological values of GRP78 and GRP94 in HB.

METHODSLiver tissue specimens from 15 children with HB and 10 specimens of normal liver tissues were obtained. EnVison immunohistochemistry was used to detect the expression of GRP78 and GRP94 in the conventional paraffin-embedded liver sections.

RESULTSThe positive rates of GRP78 expression (53% vs 10%; P<0.05) and GRP94 expression (60% vs 10%; P<0.05) in HB liver tissues were significantly higher than those in the normal liver tissues. The positive rates of GRP78 expression in the cases without lymphnode metastasis or in clinical stage I-II were significantly lower than those in the cases with lymphnode metastasis or in clinical stage III-IV (P<0.05). GRP94 showed a decreased tendency of positive expression in the cases without lymphnode metastasis or in clinical stage I-II when compared with the cases with lymphnode metastasis or in clinical stage III-IV, although there were no statistical differences between them.

CONCLUSIONSGRP78 and GRP94 expression might play important roles in the pathogenesis and progression of pediatric HB.

Child ; Child, Preschool ; Female ; Heat-Shock Proteins ; analysis ; Hepatoblastoma ; chemistry ; pathology ; Humans ; Immunohistochemistry ; Infant ; Liver ; chemistry ; Liver Neoplasms ; chemistry ; pathology ; Male ; Membrane Glycoproteins ; analysis ; Neoplasm Staging

OBJECTIVETo study the effects of Qushi Huayu Decoction (QHD) contained serum on fatty deposition and tumor necrosis factor alpha (TNF-alpha) secretion of hepatic lipotoxicity model in vitro, for further investigating the mechanism of the decoction for preventing and treating fatty liver.

METHODSThe steatosis with TNF-alpha secretion lipotoxic model of HepG2 induced by long-chain free fatty acid (FFA) was duplicated. Groups of normal, model cells and model cells treated with different concentrations of QHD contained serum were set up to test the content of TNF-alpha in culture supernate and triglyceride (TG) in cells, as well as to observe the ultrastructural change of cells by oil-red staining and the protein expression and gene expression of cellular TNF-alpha.

RESULTSAfter being stimulated with FFA for 24 h, marked deposition of lipid with high content of TG presented in the cells of model group. Compared with the normal group, not only TNF-alpha content of culture supernate but also the protein expression and mRNA expression of intracellular TNF-alpha increased significantly. Contrast to the model group, the contents of TG in cells and TNF-alpha in supernate as well as the protein and mRNA expression of TNF-alpha in the model cell group treated with 10% QHD were lower significantly (all P < 0.01).

CONCLUSIONQHD could significantly inhibit the fatty deposition and TNF-alpha secretion in HepG2 cells induced by free fatty acid.

Animals ; Blotting, Western ; Cell Line, Tumor ; Drugs, Chinese Herbal ; pharmacology ; Fatty Acids ; pharmacology ; Hepatoblastoma ; genetics ; metabolism ; pathology ; Humans ; Liver Neoplasms ; genetics ; metabolism ; pathology ; Microscopy, Electron, Transmission ; RNA, Messenger ; biosynthesis ; genetics ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction ; Serum ; Triglycerides ; metabolism ; Tumor Necrosis Factor-alpha ; genetics ; metabolism

Autopsy ; Female ; Hepatoblastoma ; diagnosis ; diagnostic imaging ; pathology ; Humans ; Infant, Newborn ; Liver Neoplasms ; diagnosis ; diagnostic imaging ; pathology ; Neoplasm Staging ; Rare Diseases ; Tomography, X-Ray Computed

The undifferentiated (embryonal) sarcoma of the liver (USL) has previously been called malignant mesenchymoma, undifferentiated sarcoma and fibromyxosarcoma. USL was named as an entity by Stocker and Ishak in 1978 on the basis of an Armed Forces Institute of Pathology (AFIP) series of 31 cases. The USL is a rare primary neoplasm of a mesenchymal origin and it predominantly occurs in children. Stocker reported that it was fourth in frequency among the liver tumors of childhood, following hepatoblastoma, hemangioendothelioma and hepatocellular carcinoma. Although there has been controversy as to the most appropriate treatment, the studies have reported that long term survival is possible after complete surgical resection with or without perioperative chemotherapy. This tumor's frequency in the adult population is extremely low. We report here on a case of USL in an adult woman with the review of the relevant literature.
Adult* ; Arm ; Carcinoma, Hepatocellular ; Child ; Drug Therapy ; Female ; Hemangioendothelioma ; Hepatoblastoma ; Humans ; Liver Neoplasms ; Liver* ; Mesenchymoma ; Neoplasms, Germ Cell and Embryonal ; Pathology ; Sarcoma*