Malignant Liver Tumor In Children Research Articles

Feeding artery characteristics and enhancement patterns of hepatoblastoma patients treated with transarterial chemoembolization (TACE): Digital subtraction angiography evaluation.

Hepatoblastoma is one of the most common primary malignant liver tumors in children. The incidence of hepatoblastoma has been increasing, reaching 1.2 per million children now. The transarterial chemoembolization (TACE) procedure is one of the most practical and effective treatment options besides surgery. Digital subtraction angiography (DSA) is performed as the first step of the TACE procedure. The aim of this study was to provide information about the feeding arteries and enhancement pattern of the hepatoblastoma that was assessed by DSA before the TACE procedure. A retrospective study was conducted among hepatoblastoma cases that had undergone DSA on the TACE procedure to obtain information on the vascularity of the tumor. A total of 26 hepatoblastoma cases who had DSA examination as a part of their first TACE procedure were included, consisting of 15 boys and 11 girls, aged between 1-15 years. All cases were stage III and IV according to the Pre-Treatment Extent of Tumor (PRETEXT) staging classification. All hepatoblastoma cases had multiple feeding arteries, most of which were branches of the right hepatic artery. The largest diameter of the feeding artery was 1.82 mm, and the smallest was 0.63 mm. Most cases (84.62%) had strong contrast absorption, and spread evenly, either at the edges or in the center of the tumor. DSA is believed to be an accurate procedure to provide a detailed description of the feeding artery; enhancement patterns of hepatoblastoma were influenced by an adequate TACE.

Treatment Outcomes for Hepatoblastoma: 15-Years-Experience of a Single Institution – Sheikh Khalifa Medical City, Abu Dhabi, UAE

Background: Hepatoblastoma is the most common malignant liver tumor in children. Treatment protocols varies. In our center, we have adopted the Children’s Oncology Group (COG) AHEP0731 protocol, in addition to some experimental regimens for relapsed solid tumors. Methods: We aimed to investigate the outcome of the current hepatoblastoma treatment protocol at our center. 15 patients were included between January 2008 and June 2023. A retrospective review was carried to review the clinical presentation, serum α-fetoprotein (AFP) level at diagnosis, histological subtype, treatment, and outcomes. Results: 12 patients (80%) were symptomatic at time of diagnosis, with abdominal mass being the most common presenting complaint. Nine patients (60%) presented in stage 3 PRETEXT staging system. Epithelial histopathological subtype was predominant subtype. Thirteen patients have received preoperative chemotherapy, followed by surgical resection; only one patient underwent upfront surgical resection followed by chemotherapy. Preoperative chemotherapy consists of 2 to 4 cycles of Cisplatin, Fluorouracil, Vincristine and Doxorubicin (C5VD), followed by surgical resection. Four of them underwent neoadjuvent experimental chemotherapy utilizing agents such as Pazopanib, Pembrolizumab and Sorafenib. During followup, six patients died of progressive disease. The median survival time was 42 months (95% confidence interval: 18–42%). Five-year overall survival was 44.09% (95% confidence interval: 18–42%). Conclusions: The combination of surgery and chemotherapy for hepatoblastoma is an effective approach. Utilization of new-targeted therapies and relapsed solid tumors regimens may prolong life in patients who did not respond to standard therapy. Further studies are required to validate its usage on patients with advanced hepatoblastoma.

Differential diagnosis of benign and malignant liver tumors in children using the method of quantitative assessment of multiparametric magnetic resonance imaging data

Differential diagnosis of benign and malignant liver tumors in children using the method of quantitative assessment of multiparametric magnetic resonance imaging data

Upregulation of SERPINE2 Results in Poor Prognosis of Hepatoblastoma via Promoting Invasion Abilities.

Hepatoblastoma (HB) is the most common malignant liver tumor in children. High-risk patients, especially those with tumor metastasis, have poor prognosis. Serpin family E member 2 (SERPINE2) is overexpressed in a variety of tumors, especially adenocarcinoma, and promotes tumor invasion and metastasis. The function and mechanism of SERPINE2 in HB are still unclear. The purpose of this study was to investigate the potential clinical prognostic value and molecular mechanism of SERPINE2 in HB. We performed bioinformatics analyses on HB microarray data GSE131329 to study the role of SERPINE2. The expression level of SERPINE2 in HB and its clinical significance were further analyzed by quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, and immunohistochemistry. After constructing the SERPINE2 overexpression and knockdown in HepG2 and HUH6 cells, the 5-ethynyl-29-deoxyuridine (EdU) assay, wound healing assay, Transwell experiment, and apoptosis assay were performed to explore the role of SERPINE2 in HB progress. Upregulation of SERPINE2 was found in HB tissues and was associated with a poor prognosis. Moreover, the SERPINE2 expression was related to tumor size, vascular invasion, and tumor metastasis. The Cox regressions show that high SERPINE2 expression is an independent risk factor for HB. SERPINE2 overexpression remarkably enhanced HB cell migration and invasion and suppressed apoptosis, while knockdown of SERPINE2 exerted the opposite effect. In addition, SERPINE2 facilitated the epithelial to mesenchymal transformation (EMT) phenotype of HB cells in vitro. Our findings indicated that SERPINE2 accelerates HB progression, suggesting that SERPINE2 may be a potential prognostic biomarker and an underlying therapeutic target for HB.

Recent advances in surgical strategies and liver transplantation for hepatoblastoma.

Hepatoblastoma (HB) is the most common malignant liver tumor in children. Although the development of treatment strategies with advances in chemotherapy has greatly improved the prognosis of HB, surgical resection and liver transplantation still play a vital role in the treatment of HB. In recent years, technological innovations have led to the development of new surgical approaches for HB. In this review, we describe the latest research on the surgical management of HB, including new imaging technologies, minimally invasive approaches, and the application of associating liver partition portal vein ligation for staged hepatectomy. We also discuss the current role of liver transplantation, use of ante-situm or ex-situ liver resection with auto-transplantation, and management of metastatic HB.

TREATMENT/MANAGEMENT OF OTHER HEPATIC TUMORS

Pediatric liver neoplasias are rare, comprising 1–4% of all solid childhood tumors. More than half of these masses are due to hepatoblastoma and hepatocellular carcinomas, making remaining various liver tumors much more rarer. Hepatic mesenchymal hamartoma (HMH) is a benign tumor observed in children less than five- year-old. It is located in the right lobe of the liver more often. It has a cystic structure, and AFP is generally normal or slightly elevated. The treatment is complete resection. In rare cases, HMH can transform into undifferentiated embryonal sarcoma. Focal nodular hyperplasia is a well-circumscribed benign lesion, which is usually discovered incidentally as well as with oral contraceptive use, postchemotherapy status, and hereditary hemorrhagic telengiectasia. Typical imaging finding is a central scar in the mass lesion, which might overlap with fibrolamellar hepatocellular carcinoma. Asymptomatic cases might be managed with an expectant approach by careful monitoring whereas symptomatic cases might be treated with surgery or ablation therapy. Infantile hemangioma is the most common benign hepatic tumor in infancy. Symptoms at admission may include abdominal distention due to hepatomegaly, congestive heart failure, feeding problems, anemia, thrombocytopenia and consumptive coagulopathy, jaundice. Many of these hemangiomas are discovered incidentally and are localized. In most cases, these lesions are small enough to be of no clinical significance. In severe cases, propranolol, corticosteroids, mTOR inhibitors or cytotoxic agents can be used for treatment. Undifferentiated embryonal sarcoma of the liver (UESL) is the third most common malignant liver tumor in children. The median age of diagnosis of UESL is 10,5 years, in comparison to that of liver rhabdomyosarcoma which is 3.6 years. UESL is an aggressive malignancy that should be treated with multimodal therapy. Most important prognostic factor is the completeness of the resection. The survival is reported to range between 70% and 90% in various case series. Rhabdomyosarcomas are observed in the biliary tract. The usual sign in admission is obstructive jaundice with or without abdominal mass. Treatment is multimodal therapy. With CWS protocols, the 5-year overall (OS) and event free survival (EFS) rates were 58% and 47%, respectively. Hepatic angiosarcoma is a rare but highly aggressive malignancy of endothelial cells, previously known as infantile hemangioendothelioma type 2. There is a girl predominance. Despite multiagent aggressive treatment approaches including liver transplantation, the overall prognosis is still poor.

The function of Piezo1 in hepatoblastoma metastasis and its potential transduction mechanism

BackgroundHepatoblastoma (HB) is the most common primary malignant liver tumor in children. The prognosis of HB metastasis is poor, despite the increasing diversity of treatment. Piezo, a ubiquitously expressed membrane mechano-transduction protein, is involved in the process of tumor cell migration. Under the gene expression profiling interactive analysis (GEPIA) database, Piezo1 was highly expressed in HB and negatively correlated with the overall survival time. MethodsFirstly, the expression of Piezo1 in both paracancerous and HB tissues (n = 7) was detected, and the prognostic value of Piezo1 was assessed in HB (n = 160) patients. Secondly, the inhibition and overexpression of Piezo1were executed in two HB cell lines, HepG2 and Huh 6. Methyl thiazolyl tetrazolium (MTT), wound healing and trans-well assays were performed to identify the effect of Piezo1 on the proliferation and metastasis of HB cells, respectively. In addition, a co-immunoprecipitation assay was performed to determine whether Piezo1 has an interaction with HIF-1α. Finally, the expressions level of Piezo1, HIF-1α, and VEGF by overexpression/inhibition each other were detected by RT-qPCR and western blots to find a possible signaling channel in HB metastasis. ResultsWe found that Piezo1 was highly expressed in HB tissues and associated with poor prognosis of patients. Piezo1 was related to cell proliferation in HepG2 and Huh 6 cells. We also found that Piezo1 stimulated HIF-1α expression. Meanwhile, overexpression of Piezo1 promoted the migration and invasion of HB cells, while the promotion was not detected when HIF-1α was suppressed. Additionally, the silencing of HIF-1α inhibited the expression of VEGF, but showed no effect on Piezo1 expression. ConclusionIn this study, we identified that Piezo1 was involved in HB metastasis, and the Piezo1-HIF-1α-VEGF axis could be a possible signaling pathway in HB metastasis.

USP7 promotes hepatoblastoma progression through activation of PI3K/AKT signaling pathway.

Hepatoblastoma (HB) is an embryonic solid tumor and the most common primary malignant liver tumor in children. HB usually occurs in infants and children. Although treatment diversity is increasing, some patients still have very poor prognosis. Many studies have investigated USP7 inhibitors for tumors. Using database information, we found that USP7 is highly expressed in HB. Lentivirus-mediated USP7 knockdown and overexpression was performed in HB cell lines HepG2 and Huh6. CCK8 and transwell assays were used to determine cell viability and metastasis. Flow cytometry was used to study cell cycle and apoptosis. Levels of proteins were detected using western blots. Downregulation of USP7 resulted in significant decrease in cell proliferation, clonal formation, and cell migration and invasion. With overexpression of USP7, cellular malignant behavior increased. Cell cycle assays showed that USP7 knockdown inhibited G1 to S phase transition in the cell cycle. Upregulation of USP7 promoted the transition. Animal experiments showed USP7 facilitated tumor growth in vivo. Western blots indicated that USP7 may affect HB tumorigenesis through the PI3K/AKT signaling pathway. Furthermore, USP7 inhibitor P5091 inhibited HB development and PI3K/AKT pathway. USP7 upregulation contributed to HB genesis and development through the PI3K/AKT signaling pathway. USP7 could be a potential target for future HB treatment.

Hepatoblastoma relapses after front-line therapy according to SIOPEL protocols: clinical characteristics and outcome

Hepatoblastoma (HB) is the most common primary malignant liver tumor in children. Relapses of HB are rare and make up no more than 12% of cases among patients who have achieved complete response after the first-line therapy. The aim of the study was to analyze the incidence, clinical characteristics and outcome of HB relapses in patients treated according to SIOPEL protocols. This study is supported by the Independent Ethics Committee and approved by the Academic Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology. 74 patients with HB were treated for the period 02.2012–12.2018 (82 months). Patients were stratified and treated according to SIOPEL protocols. Relapses were detected in 7/70 (10,0%) patients, who achieved complete response after front-line therapy. We analyzed demographic data, initial tumor characteristics, details of front-line therapy, characteristics of HB relapses and treatment of relapse. Median age at the time of diagnosis of HB was 13,3 (range 0,6–62,9) months. Male:female ratio – 1:0,4. The distribution by PRETEXT stages: II – 2 (28,6%), III – 1 (14,3%), IV – 4 (57,1%). 4 (57,1%) patients had distant metastases. Patients were stratified to standard-risk group – 2 (28,6%) and high-risk group – 5 (71,4%). 3 (42,8%) underwent liver transplantation (LT). Median age at the time of relapse was 33,5 (range 11,9–74,4) months. Median time from the completion of front-line therapy to relapse – 5,3 (range 3,2–19,1) months. Median AFP level at relapse – 35,0 (range 1,8–34160,4) ng/ml. Methods of relapse detection: routine follow-up – 5 (71,4%), clinical symptoms – 2 (28,6%). The latter 2 patients with initially AFP-secreting HB had normal AFP levels at relapse. Pattern of relapse: systemic – 5 (71,4%), combined – 2 (28,6%). The majority of patients received irinotecan-based chemotherapy – 5 (71,4%). Chemotherapy was combined with surgery in 6 (85,7%) cases. Median follow-up time from the moment of relapse was 22,4 (range 5,2–51,3) months. Outcomes: 5 (71,4%) alive (4/5 – with no evidence of disease, 1/5 – with active disease), 2 (28,6%) died of the disease. 3-year overall survival after relapse was 66,6 ± 19,2%. The main conclusion of the study was that combination of second-line chemotherapy with surgical resections allowed achieving long-lasting survival in some HB relapsed patients, including patients who had previously undergone LT.

CLINICAL AND SUBCLINICAL FEATURES OF PEDIATRIC PATIENTS WITH HEPATOBLASTOMA AT NATIONAL CHILDREN HOSPITAL

Background: Hepatoblastoma is the most common malignant liver tumor in children. Aims: Study on clinical and subclinical features of pediatric patients with hepatoblastoma at National Children Hospital from 1/2016 to 8/2019. Materials and Methods: A total patients with operated Hepatoblastoma diagnosed by pathologists, at the Viet Nam National Children’s Hospital from January 2016 to August 2019. The study design is retrospective. Resullts: Study subject’s mean of age was 36,8 months (range 4 – 149 months), the common group of age was under 5 years old (76,7%), male’s more than female (56,7% and 43,3%). The most common clinical symptoms were hepatomegaly (50%), a palpable abdominal mass (30%), abdominal pain (13,3%), secondary anemia (13,3%), weight loss (6,7%), jaundice (3,3%). About laboratory test: 83,3% patients with anemia, 36,7% patients with thrombocytosis, 90% patients with hight GOT levels, 53,3% patients with hight GPT levels, 96,7% patients with hight serum AFP levels and the average value of AFP was 217160,7 ng/ml (range 575 – 1686328,6 ng/ml). Mean size of the tumor on computerized tomography was 5,48cm (range 2 – 15cm), 60% size of tumor ≤ 5cm, 96,7% had only one tumor, 70% primary tumor located to the right lobe of the liver, 76,7% were staged PRETEXT II, the most common hepatoblastoma histopathological subtypes was as follows: epithelial (80%). Conclusion: Clinical symptoms of hepatoblastoma are usually nonspecific. A routine check – up strategy for early detection of hepatoblastoma and the role of subclinical aids in diagnosis is very important.

LIN28B gene polymorphisms modify hepatoblastoma susceptibility in Chinese children.

Hepatoblastoma is one of the malignant liver tumors in children. However, genetic mechanisms underpinning the initiation of hepatoblastoma remain largely unclear. The previous study showed that lin-28 homolog B (LIN28B) might play a role in the development of hepatoblastoma. To detect the association between LIN28B gene polymorphisms and hepatoblastoma risk in Chinese children, we conducted a five-center case-control study of 275 hepatoblastoma patients and 1018 cancer-free controls. Four potentially functional polymorphisms were genotyped using the Taqman method. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the strength of the associations. We found that the rs314276 C>A polymorphism (AA vs. CC: adjusted OR=2.05, 95% CI=1.36-3.10, P=0.0006; AA vs. CA/CC: adjusted OR=2.11, 95% CI=1.43-3.12, P=0.0002) and rs9404590 T>G (GG vs. TT: adjusted OR=1.89, 95% CI=1.20-3.00, P=0.007; GG vs. TT/TG: adjusted OR=1.87, 95% CI=1.20-2.92, P=0.006) were associated with increased hepatoblastoma risk. Combination analysis of risk genotypes showed that patients with four risk genotypes had a higher chance of developing hepatoblastoma than carriers of 1 to 3 risk genotypes. Stratification analysis showed the significant association between the rs314276 AA genotype and hepatoblastoma risk in both age and sex groups, as well as clinical stages III+IV cases. The rs9404590 GG genotype was associated with hepatoblastoma risk in participants' ≥17 months, in females, and for those with clinical stages III+IV disease. Furthermore, four risk genotypes confer higher hepatoblastoma susceptibility in both age and sex groups, as well as groups with clinical stages III+IV disease. Genotype-based gene expression analysis confirmed that the rs9404590 T>G polymorphism was significantly associated with altered LIN28B gene expression. We further validated our findings using false-positive probability analysis. This finding suggested that LIN28B gene polymorphisms may be associated with an increased predisposition to hepatoblastoma.

Hepatoblastoma relapses with a normal level of alpha-fetoprotein: report of two cases

Hepatoblastoma (HB) is the most common malignant liver tumor in children. The level of alpha-fetoprotein (AFP) is used for monitoring the response to antitumor therapy and for diagnosing relapses. The occurrence of HB relapses with normal AFP levels in patients who had elevated levels of this tumor marker at disease onset is considered to be an uncommon situation. The aim of this study was to describe cases in which AFP-negative hepatoblastoma relapses developed. The study participants included two HB patients who were initially stratified into high-risk and standard-risk groups and who received treatment at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology and the Petrovsky National Research Center of Surgery inMoscow. At the moment of relapse acknowledgement these patients had normal AFP levels, which was confirmed by serial measurements. Immunohistochemistry (IHC) tests were performed on paired samples of the tumor at disease onset and at disease relapse respectively to evaluate AFP expression. The presented clinical cases demonstrate that normal AFP levels, when accompanied by suspicious clinical symptoms, do not allow to exclude an HB relapse. The possibility of relapse with a normal AFP level reinforces the importance of following the current plan of screening tests, which includes not only an evaluation of AFP levels, but also other tests such as a chest X-ray and an abdominal ultrasound. Parents gave their consent to use information about the child in the article.

Rare malignant liver tumors in children.

Malignant hepatic tumors in children are rare, comprising 1.3% of all pediatric malignancies. Following hepatoblastoma, hepatocellular carcinoma is the second most common. Other malignant hepatic tumors seen in childhood include those of mesenchymal origin including undifferentiated embryonal sarcoma, angiosarcoma, rhabdomyosarcoma and epithelioid hemangioendothelioma, as well as biliary tumors such as cholangiocarcinoma. Diagnosis can be challenging because of their rarity, and the recognition of distinctive imaging features for certain tumors such as epithelioid hemangioendothelioma and biliary rhabdomyosarcoma can focus the differential diagnosis and expedite the diagnostic process. A complete MRI examination with hepatocyte-specific contrast media and diffusion-weighted imaging helps to focus the differential diagnosis, and, although findings are often nonspecific, in some cases typical features on MRI can be helpful in diagnosis. Histopathological analysis is usually required for definitive diagnosis. Hepatic tumors tend to be aggressive, and full staging is imperative to establish disease extent. Significant proportions are not amenable to upfront surgical resection and often require a multimodality approach including neoadjuvant chemotherapy within a multidisciplinary setting. Facilitating complete surgical resection is usually required for better survival. In this review, we emphasize pathology and imaging features for rare liver tumors that are useful in reaching a prompt diagnosis. We also discuss general clinical findings, prognosis and management of these tumors.

Hepatoblastoma and Pediatric Hepatocellular Carcinoma: An Update.

Hepatoblastomas (HBs) and pediatric hepatocellular carcinomas (HCCs) together account for almost 80% of primary malignant liver tumors in children and adolescents/young adults. Children's Hepatic International Collaboration (CHIC), Children's Oncology Group (COG), SociétéInternationale d'Oncologie Pédiatrique (SIOP), and International Childhood Liver Tumors Strategy Group trials have contributed to define prognostic factors and risk stratification in these tumors. The recently proposed histologic International Consensus classification of HB and HCC in children based on retrospective analysis from CHIC cases represents the base to define entities with homogeneous clinicopathologic and molecular features. This review will provide a morphologic guide for the upcoming International Liver Tumor treatment trial (Pediatric Hepatic International Tumour Trial) to be conducted through several continents. There will be an emphasis on molecular features and immunohistochemical markers for the definition of the individual histologic subtypes of HB and to better characterize the group of liver tumors in the provisional category of hepatocellular neoplasm-not otherwise specified. A brief overview of HCC in children will also be provided.

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 16000ng/dL, with a sensitivity of 71.43% and a specificity of 85.71%. Multivariate analysis showed that patients with higher values of pretransplant AFP (>16000ng/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.

CEUS in paediatric hepatic lesions

Focal liver lesions (FLL) are commonly observed in adult patients and rarely reported in children. The reasons for this remain speculative and the exact data concerning the incidence of these lesions in childhood are lacking. Primary hepatic tumors are a diverse group of epithelial and mesenchymal tumors accounting for 0.5 and 2.0% of all pediatric neoplasms. Focal liver lesions in children can be benign, malignant, or indeterminate. About one-third of the pediatric primary liver masses are benign. In pediatric patients, most benign focal liver lesions are inborn and may grow like the rest of the body. Knowledge of pediatric liver diseases and their imaging appearances is essential in order to make an appropriate differential diagnosis. Selection of the appropriate imaging test is challenging, since it depends on a number of age-related factors. The presentation will focus on the most frequently encountered benign and malignant liver tumors in children (infantile hepatic hemangioendothelioma, mesenchymal hamartoma, focal nodular hyperplasia, nodular regenerative hyperplasia, and hepatocellular adenoma, hepatocellular carcinoma and metastases) .

Targeting LRH‑1 in hepatoblastoma cell lines causes decreased proliferation.

Hepatoblastoma is the most common malignant liver tumor in children. Since it is often unresectable and exhibits drug resistance, the treatment of advanced hepatoblastoma is challenging. The orphan nuclear receptor liver receptor homolog-1 (LRH-1) serves prominent roles in malignancy; however, to the best of our knowledge, the role of LRH-1 in hepatoblastoma remains unknown. In the present study, human hepatoblastoma cell lines were analyzed; the mRNA and protein expression levels of LRH-1 were significantly higher in HepG2 and HuH6 cells compared with those in HepT1 cells and control THLE-2 cells. Knockdown of LRH-1 resulted in decreased HepG2 and HuH6 cell proliferation via downregulation of cyclin D1 (CCND1) and c-Myc. Furthermore, treatment with an LRH-1 antagonist (LRA) inhibited the proliferation and colony formation of cell lines in a dose-dependent manner, and induced cell cycle arrest at G1 phase through inhibition of CCND1 expression. Finally, LRA treatment enhanced the cytotoxic effects of doxorubicin on hepatoblastoma cells. Collectively, these findings suggested that LRH-1 may have an important role in the progression of hepatoblastoma and implicated LRA as a novel, potential therapeutic agent for the treatment of hepatoblastoma.

Hepatoblastoma misdiagnosed as infantile hemangioendothelioma in a child – a case report

Infantile hemangioendothelioma (IHH) is the most common benign tumor of the liver in children, which accounts for 12% of all pediatric liver tumors, and hepatoblastoma (HBL) is the most common malignant liver tumor in children. Although they share some clinical manifestations, the treatment strategies and prognoses are quite different. The most important alternative diagnosis to IHH in children is HBL. Histopathologic confirmation of a radiologically suspected hemangioendothelioma is often obtained before medical treatment is initiated. We are presenting here a case of HBL in a 2-year-male child misdiagnosed as having IHH on imaging studies.

Pediatric hepatocellular carcinoma.

Pediatric hepatocellular carcinoma (HCC) is the second common malignant liver tumor in children after hepatoblastoma. It differs from the adult HCC in the etiological predisposition, biological behavior and lower frequency of cirrhosis. Perinatally acquired hepatitis-B virus, hepatorenal tyrosinemia, progressive familial intrahepatic cholestasis, glycogen storage disease, Alagille’s syndrome and congenital portosystemic shunts are important predisposing factors. Majority of children (87%) are older than 5 years of age. Following mass immunization against hepatitis-B, there has been a drastic fall in the incidence of new cases of pediatric HCC in the Asia-Pacific region. Management is targeted on complete surgical removal either by resection or liver transplantation. There is a trend towards improving survival of children transplanted for HCC beyond Milan criteria. Chemotherapeutic regimens do not offer good results but may be helpful for down-staging of advanced HCC. Surveillance of children with chronic liver diseases with ultrasound and alpha-fetoprotein may be helpful in timely detection, intervention and overall improvement in outcome of HCC.

Isoorientin triggers apoptosis of hepatoblastoma by inducing DNA double-strand breaks and suppressing homologous recombination repair

Hepatoblastoma (HB) is the most common malignant liver tumor in children. DNA and DNA-associated processes are one of the most important targets of chemotherapeutic agents. Isoorientin (Iso), a natural flavonoid compound, can be extracted from several plant species. The effects of Iso and its molecular mechanisms on hepatic malignancies remain unclear. Herein, the anti-tumor effects of Iso in HB and its underlying mechanisms were explored. We found that Iso significantly inhibited the proliferation of HB cells both in vitro and in vivo. Mechanistic studies showed that Iso triggered cell apoptosis by inducing DNA double-stranded breaks and blocking the initiation process of homologous recombination repair, which was related to the attenuation of ataxia telangiectasia mutated (ATM) activation and inhibiting the binding of phosphorylated ataxia telangiectasia mutated (pATM) and the MRE11-RAD50-NBS1 (MRN) complex. Furthermore, Iso markedly sensitized HB cells to the anti-proliferative effects of the poly ADP-ribose polymerase (PARP) inhibitor olaparib both in vivo and in vitro. Taken together, our study first showed that Iso was a DNA-damage agent, and the combination of Iso with a PARP inhibitor might be a promising strategy for treating HB patients.