Primary Liver Tumors In Children Research Articles

Risk for Recurrence in Long-Term Follow-Up of Children after Liver Transplantation for Hepatoblastoma or Hepatocellular Carcinoma.

The aim of this study was to assess the long-term results of liver transplantation (LT) in pediatric patients with unresectable hepatoblastoma (HB) or hepatocellular carcinoma (HCC) with special reference to the risk of tumor recurrence. We retrospectively analyzed data from 46 HB and 26 HCC patients who underwent LT between 1990 and 2022. In HCC patients, we compared outcomes depending on donor type. We evaluated the impact of a number of risk factors on recurrence-free survival after LT. Estimated patient survival after 5, 10, and 15 years was 82%, 73%, and 73% in the HB group and 79%, 75%, and 75% in the HCC group, respectively (p = 0.76). In the HCC group, living donor LT (LDLT) and deceased donor LT (DDLT) provided similar patient survival (p = 0.09). Estimated recurrence-free survival in patients who had three or fewer risk factors was significantly better than in patients with more than three risk factors (p = 0.0001). Adequate patient selection is necessary when considering LT for primary liver tumors in children. The presence of more than three risk factors is associated with a very high risk of recurrence and indicates poor prognosis, whereas extrahepatic disease may be considered a contraindication for transplantation.

Mesenchymal Hamartoma of the Liver Associated with Discontinuity of the Vena Cava

Primary liver tumors in children are infrequent, accounting for 0.5-2 % of all pediatric neoplasms. About two-thirds are malignant. The most common pediatric malignant liver tumours are, in order of frequency, hepatoblastoma, hepatocellular carcinoma, and embryonic sarcoma of the liver. Among benign tumors, the most frequent are hemangioendothelioma and mesenchymal hamartoma of the liver, and more rarely focal nodular hyperplasia and hepatocellular adenoma [1,2]. We report the case of an infant who was entrusted to us for the management of a large liver tumor. Radiology (CT scan and MRI), in addition to the elements in favor of a mesenchymal hamartoma of the right liver revealed a congenital anomaly associated, in this case, with the absence of the inferior vena cava in its intraabdominal portion. A right hepatectomy enlarged to segment IV was performed. The right renal vein drained into the right suprahepatic vein was preserved. Note that this tumor represents 50% of the total weight of the patient, which explains the difficulties and constraints that hindered the development and quality of life of the young patient.

Surgical perspectives of primary liver tumors in children: A series of 76 consecutive cases

Surgical perspectives of primary liver tumors in children: A series of 76 consecutive cases

Molecular Mechanisms of Hepatoblastoma.

Hepatoblastoma (HB) is the predominant primary liver tumor in children. While the prognosis is favorable when the tumor can be resected, the outcome is dismal for patients with progressed HB. Therefore, a better understanding of the molecular mechanisms responsible for HB is imperative for early detection and effective treatment. Sequencing analysis of human HB specimens unraveled the pivotal role of Wnt/β-catenin pathway activation in this disease. Nonetheless, β-catenin activation alone does not suffice to induce HB, implying the need for additional alterations. Perturbations of several pathways, including Hippo, Hedgehog, NRF2/KEAP1, HGF/c-Met, NK-1R/SP, and PI3K/AKT/mTOR cascades and aberrant activation of c-MYC, n-MYC, and EZH2 proto-oncogenes, have been identified in HB, although their role requires additional investigation. Here, we summarize the current knowledge on HB molecular pathogenesis, the relevance of the preclinical findings for the human disease, and the innovative therapeutic strategies that could be beneficial for the treatment of HB patients.

Histomorphological patterns of hepatoblastoma in a tertiary care hospital.

Hepatoblastoma (HB), rare malignancy in itself, is the most common primary liver tumor in children. Most common presenting features are abdominal distension or abdominal mass. Several patterns are associated with HB with different prognosis. Furthermore, some patterns have overlapping features with other childhood tumors. The aim of this study is to discuss various patterns of HB which we came across in a tertiary care hospital during our study. H and E slides were reviewed with respect to different patterns, postchemotherapy changes including extramedullary hematopoiesis, necrosis, osteoid metaplasia, necrosis, and fibrosis. Different patterns of HB should be kept in mind by the pathologists to avoid any misdiagnosis.

Pattern and Outcome of Primary Liver Tumors in Children: Eight–year experience at South Egypt Cancer Institute

Pattern and Outcome of Primary Liver Tumors in Children: Eight–year experience at South Egypt Cancer Institute

The association of hepatoblastoma, prematurity and cerebral palsy: Case reports

Hepatoblastoma is the most common primary liver tumor in children and has a greater incidence in children with a history of prematurity and very low birth weight. To increase awareness of the association between prematurity and hepatoblastoma for health care providers who treat children with Cerebral Palsy (CP), we present two case reports. Two case reports of premature, very low birth weight infants with hepatoblastoma are described and a literature review of hepatoblastoma in the setting of prematurity and cerebral palsy is performed. Each patient had a history of 26-28 week prematurity, very low birth weight, and CP. Both presented with worsening constipation and abdominal distension that did not respond to oral medications. Appropriate referrals to the ER were made which lead to a diagnosis of hepatoblastoma. Pediatric rehabilitation was a source of referral for diagnosis in one patient and aided in the rehabilitation course following treatment for both patients. Hepatoblastoma is the most common primary liver tumor in children and has an increased incidence in children with a history of prematurity and very low birth weight. Providers who frequently care for the very low birth weight and premature children with CP should be aware of this correlation and include hepatoblastoma in the differential when managing patients with suddenly worsening constipation or abdominal distension. Pediatric physiatrists and other providers for these patients could be a source of referrals and diagnosis leading to timely treatment.

Hepatoblastoma experience in terms of surgery

Introduction: Although hepatoblastoma is a rare tumor, it is the most common abdominal malignant tumor after nephroblastoma and neuroblastoma in children under 3 years of age. In addition, 95% of primary liver tumors in children are hepatoblastoma.
 In this study, we aimed to present the patients with hepatoblastoma who had undergone surgery.
 Materials and Methods: Patients who were operated for hepatoblastoma in the last 10 years at Çukurova University Hospital were included in the study. Age, gender, complaints, blood Alpha Feto Protein (AFP) levels, whether or not neoadjuvant chemotherapy, size, stage, surgical findings, the presence of distant metastasis, post-operative complication, follow-up, and mortality were evaluated.
 Results: We operated on 22 patients with hepatoblastoma in the last 10 years. We have access to 17 patients’ data. The mean age of the patients was 22.4 years (4 months - 8 years). 88% of the patients were younger than 5 years old and 76% were younger than 3 years of age. Seven patients were male and 10 were female. Fourteen patients presented with abdominal distention and swelling. One was admitted to the hospital with weight loss, one with diarrhea and one with fever. In the first evaluation, 8 patients were stage 2 and 9 patients were stage 3 according to PRETEXT staging. We did not have stage 1 or 4 patients. Two patients had a tumor in the caudate lobe. AFP levels were high in 16 patients. The mean size of the mass was 11.5 cm in the first evaluation. The tru-cut biopsy was performed all the patients before taking neo-adjuvant chemotherapy. Thereafter, the patients underwent surgery. One patient was undergoing surgery for trans-arterial chemo-embolization (TACE) due to the fact that the tumor could not be excised after chemotherapy, and after TACE, the tumor was able to totally removed. In one patient, the surgical margin was excised positively due to the invasion of the vena cava. Two patients had portal vein thrombus and one was excised during surgery. Seven patients had right, 3 patients had right expanded, 3 patients had left expanded, 1 patient had segment 6-7 and 3 patients had left hepatectomy. The distant metastasis was in 2 patients (lungs). Mortality was in 1 patient.
 Conclusion: Multidisciplinary approach is very important in hepatoblastoma and other malignant masses. Not only pediatric oncology but also alternative treatment options such as trans-arterial chemotherapy should be evaluated.

Targeting PIM Kinases Affects Maintenance of CD133 Tumor Cell Population in Hepatoblastoma

Hepatoblastoma is the most common primary liver tumor in children, but treatment has not changed significantly in the past 20 years. We have previously demonstrated that Proviral Integration site for Moloney murine leukemia (PIM) kinases promote tumorigenesis in hepatoblastoma. Stem cell-like cancer cells (SCLCCs) are a subset of cells thought to be responsible for chemoresistance, metastasis, relapse, and recurrence. The aim of this study was to identify SCLCCs in hepatoblastoma and determine the role of PIM kinases in SCLCCs. Hepatoblastoma cells were separated into CD133-enriched and CD133-depleted populations and the frequency of SCLCCs was assessed. CD133 expression was determined in the presence or absence of the PIM inhibitor, AZD1208. The effects of AZD1208 on proliferation, apoptosis, and motility were assessed in vitro and the effect of AZD1208 on tumor growth was examined in vivo. We identified CD133 as a marker for SCLCCs in hepatoblastoma and showed that PIM kinases promote a SCLCC phenotype. PIM kinase inhibition with AZD1208 decreased proliferation, migration, and invasion and increased apoptosis in both SCLCCs and non-SCLCCs in a long-term passaged hepatoblastoma cell line and patient-derived xenograft. Additionally, tumor growth in mice implanted with hepatoblastoma SCLCCs was decreased with PIM inhibition such that 57% of the tumors regressed. These findings identify CD133 as a marker for SCLCCs in hepatoblastoma and provide evidence that inhibition of PIM kinases decreases stemness and tumorigenicity of SCLCCs in hepatoblastoma, making them potential therapeutic targets for the treatment of hepatoblastoma.

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 26months (IQR: 15-44). Graft survival was 96%, 87%, and 80% at 1, 3, and 5years, 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 3.9years. Of three patients who underwent salvage transplants, two are alive at 1.5years after transplant. Non-survivors were associated with lower median alpha fetoprotein value at presentation compared to survivors (21707 vs 343214; 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.

Pattern and Outcome of primary Liver Tumors in Children: A 10 years report from single oncology center in Upper Egypt

Primary malignant liver tumors are uncommon in children with hepatoblastoma (HB) andhepatocellular carcinoma (HCC) are the most common.

Pattern and Outcome of primary Liver Tumors in Children: A 10 years report from single oncology center in Upper Egypt

Pattern and Outcome of primary Liver Tumors in Children: A 10 years report from single oncology center in Upper Egypt

Hepatoblastoma Biology Using Isotope Ratio Mass Spectrometry: Utility of a Unique Technique for the Analysis of Oncological Specimens.

Hepatoblastoma is the most common primary liver tumor in children. However, it occurs rarely, with an incidence of 0.5-1.5 cases per million children. There is no clear explanation of the relationship between clinicopathologic features, therapy, and outcome in hepatoblastoma cases, so far. One of the most widely accepted prognostic factors in hepatoblastoma is histology of the tumor. The aim of the study was to determine the potential differences in biology of hepatoblastoma histological subtypes at the atomic level using the unique method of isotope ratio mass spectrometry, which is especially valuable in examination of small groups of biological samples. Twenty-four measurements of nitrogen stable isotope ratio, carbon stable isotope ratio and total carbon to nitrogen mass ratio in fetal and embryonal hepatoblastoma tissue were performed using a Sercon 20-22 Continuous Flow Isotope Ratio Mass Spectrometer (CF-IRMS) coupled with a Sercon SL elemental analyzer for simultaneous carbon-nitrogen-sulfur (NCS) analysis. A difference of about 1.781‰ in stable nitrogen isotope 15N/14N ratio was found between examined hepatoblastoma histological subtypes. The prognosis in liver tumors cases in children may be challenging particularly because of the lack of versatile methods of its evaluation. Isotope ratio mass spectrometry allows one to determine the difference between hepatoblastoma histological subtypes and clearly indicates the cases with the best outcome.

Benefit of early inflow exclusion during living donor liver transplantation for unresectable hepatoblastoma

BackgroundHepatoblastoma (HB) is a highly malignant primary liver tumor in children. Although liver transplantation (LT) is an effective treatment for unresectable HB with good long-term outcomes, post-transplant survival is mainly affected by recurrence, despite adjuvant chemotherapy. Novel strategies are needed to improve the outcomes in patients undergoing LT for unresectable HB. Patients and methodsTwelve children received LT for unresectable HB. In 9 patients, we applied early exclusion of hepatic inflow (hepatic artery and portal vein) and creation of a temporary portocaval shunt during LT. ResultThere were differences in the duration of and the blood loss during operation as compared with previously reports. The estimated glomerular filtration rate was well preserved at 3, 6, and 12months and the latest follow-up after LT, and the recurrence-free survival was 88.9%. ConclusionEarly inflow control during LT for unresectable HB may benefit recurrence-free survival by minimizing blood loss and tumor dissemination, preserving renal function and allowing early adjuvant chemotherapy.

Pediatric hepatoblastoma: diagnosis and treatment.

Hepatoblastoma (HBL) is the most common primary liver tumor in children, and is usually diagnosed during the first 3 years of life. Collaborative multicenter studies have led to improved diagnostic and treatment strategies. The pretreatment extent of disease (PRETEXT) staging system has become a consensus classification, and an international pathological classification system has also been developed. Clinical trials examining multimodal therapy, which consists of complete surgical resection plus liver transplantation and chemotherapy, have led to improved outcomes for children with HBL. Recently, the Children's Hepatic Tumors International Collaboration (CHIC), which includes major multicenter study groups, created a shared database that merges data on all children underwent therapy in the clinical trials of these groups until 2008. CHIC has developed a global approach to risk stratification of pediatric HBL for use in future global clinical trials. The aim of this review is to report the recent developments on the diagnosis and treatment of pediatric HBL.

Exome sequencing of hepatoblastoma reveals novel mutations and cancer genes in the Wnt pathway and ubiquitin ligase complex.

Hepatoblastoma (HB) is the most common primary liver tumor in children. Mutations in the β-catenin gene that lead to constitutive activation of the Wnt pathway have been detected in a large proportion of HB tumors. To identify novel mutations in HB, we performed whole-exome sequencing of six paired HB tumors and their corresponding lymphocytes. This identified 24 somatic nonsynonymous mutations in 21 genes, many of which were novel, including three novel mutations targeting the CTNNB1 (G512V) and CAPRIN2 (R968H/S969C) genes in the Wnt pathway, and genes previously shown to be involved in the ubiquitin ligase complex (SPOP, KLHL22, TRPC4AP, and RNF169). Functionally, both the CTNNB1 (G512V) and CAPRIN2 (R968H/S969C) were observed to be gain-of-functional mutations, and the CAPRIN2 (R968H/S969C) was also shown to activate the Wnt pathway in HB cells. These findings suggested the activation of the Wnt pathway in HB, which was confirmed by immunohistochemical staining of the β-catenin in 42 HB tumors. We further used short hairpin RNA (shRNA)-mediated interference to assess the effect of 21 mutated genes on HB cell survival. The results suggested that one novel oncogene (CAPRIN2) and three tumor suppressors (SPOP, OR5I1, and CDC20B) influence HB cell growth. Moreover, we found that SPOP S119N is a loss-of-function mutation in HB cells. We finally demonstrated that one of the mechanisms by which SPOP inhibits HB cell proliferation is through regulating CDKN2B expression. These results extend the landscape of genetic alterations in HB and highlight the dysregulation of Wnt and ubiquitin pathways in HB tumorigenesis.

Role of liver transplantation in the management of hepatoblastoma in the pediatric population.

Hepatoblastoma (HB) is the most common primary liver tumor in children and accounts for two-thirds of all malignant liver neoplasms in the pediatric population. For patients with advanced HB (unresectable or unresponsive to chemotherapy), combined treatment with chemotherapy and liver transplantation is an excellent option. The etiology of HB is mostly obscure because of its extreme rarity although some inherited syndromes and very low birth weight have been associated with it. The prognosis for children with HB has significantly improved in the past three decades thanks to advancements in chemotherapy, surgical resection and postoperative care. In 2002 a surgical staging system called pretreatment extent of disease (PRETEXT) was designed to allow a universal, multidisciplinary approach to patients with HB. Between one-third to two-thirds of patients initially present with unresectable tumors or distant metastases, but up to 85% of these tumors become operable after neoadjuvant chemotherapy. Patients with PRETEXT categories 1, 2, and some 3 are referred for neoadjuvant chemotherapy followed by surgical resection with the goal of complete tumor removal. Classic treatments regimens include a combination of cisplatin, fluorouracil, and vincristine or cisplatin and doxorubicin. Liver transplantation is the only treatment option for unresectable HB. In 2010 the pediatric end-stage liver disease, a pediatric-specific scoring system that determines a patient's ranking on the liver transplant list, began to award additional "exception" points for patients with HB. We analyzed the Standard Transplant Analysis and Research dataset to assess the impact of changes in exception point criteria for HB on outcomes after liver transplantation at Texas Children's Hospital in Houston, Texas. We found that patients who were listed for transplantation with current HB exception criteria experienced a shorter waitlist time but survival was similar between the two eras.

Surgical treatment of primary liver tumors in children: Outcomes analysis of resection and transplantation in the SEER database

Adjusted survival outcomes following hepatic resection and transplantation for pediatric liver tumors have not been compared. To address this question, we conducted a retrospective cohort study using the SEER registry. While SEER lacks certain specifics regarding staging, chemotherapy, comorbidities, and recurrence, important hypothesis-generating data are available and were analyzed using Kaplan-Meier statistics and Cox proportional hazards regression. All SEER patients under the age of 20yr undergoing surgery for HB (n=318) or HCC (n=80) between 1998 and 2009 were included. Of HB patients, 83.3% underwent resection and 16.7% transplantation. Advanced disease, vascular invasion, and satellite lesions were more common among transplant patients. Unadjusted five-yr survival was equivalent, as was the adjusted hazard of death for transplant relative to resection (HR=0.58, p=0.63). Of HCC patients, 75.0% underwent resection and 25.0% transplantation. Transplant patients had a higher prevalence of vascular invasion and satellite lesions. Five-yr survival was 53.4% after resection and 85.3% after transplant, and the adjusted hazard of death was significantly lower after transplantation (HR=0.05, p=0.045). While transplantation is generally reserved for unresectable tumors, the favorable survival seen in HCC patients suggests that liberalized transplant criteria might improve survival, although further prospective data are needed.

Current concepts in pediatric liver tumors

Liver tumors in children can be classified into benign or malignant; some of the benign lesions can have the potential of malignant transformation, and therefore the therapeutic approach may change. These neoplasms account for nearly 1-2% of all pediatric tumors and they have gained significant attention in the last decades due to data suggesting that the incidence may be increasing 5% annually. We know that with new and improved imaging modalities some of these lesions may be detected more often than before. Recent studies showed that liver cancer represented 2% of malignancies in infants by 1980s and this was doubled in incidence to 4% in the following 10 yr. In this review our aim is to discuss all primary liver tumors in children with attention to their clinicopathological and immunohistochemical features followed by the current standard of care.

Multiple hepatic mesenchymal hamartomas in a premature associated with placental mesenchymal dysplasia

Placental mesenchymal dysplasia (PMD) is an uncommon disorder that has to be differentiated histologically from a partial mole. In contrast to a hydatitiform mole, PMD can coexist with a viable fetus. Placental mesenchymal dysplasia is characterized by placentomegaly and dilatation of the chorionic vessels. In our case, multiple hepatic mesenchymal hamartomas in a preterm were associated with PMD. This association is an extremely rare anomaly. Mesenchymal hamartomas occur in 5% of all primary liver tumors in children and are generally benign lesions.