A rare case of mixed adult Hepatoblastoma mimicking as Hepatocellular Carcinoma

@#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.

Clinical characteristics and prognosis of 83 children with newly treated hepatoblastoma / 中华儿科杂志

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.

Resultados del tratamiento del hepatoblastoma en los Andes Ecuatorianos / Results of the treatment of hepatoblastoma in the Ecuadorian Andes

RESUMEN: El hepatoblastoma (HB), es una neoplasia maligna, que se origina en el hígado. La supervivencia (SV) depende de la extensión de avance de la enfermedad. El objetivo de este estudio fue determinar diferencias en la SV actuarial global (SVAG) y libre de enfermedad (SVLE) en pacientes con HB, según la extensión de su enfermedad. Serie de casos con seguimiento. Se incluyeron pacientes de entre 4 y 160 meses de edad tratados en un centro oncológico de Los Andes ecuatorianos (2000-2019). Las variables resultado fueron: lóbulo afectado, metástasis pulmonar, infiltración vascular, estadio PRETEXT, riesgo, histología, niveles de alfafetoproteína (AFP), remisión completa (RC), SVAG y SVLE. Se utilizó estadística descriptiva y analítica (Chi2, exacto de Fisher y corrección por continuidad). Se realizaron análisis de SV con curvas de Kaplan Meier y log-rank. Fueron estudiados 28 pacientes (53,6 % hombres), con una mediana de edad de 40 meses. Se verificaron metástasis pulmonares e infiltración vascular en el 25,0 % y 35,7 % de los casos respectivamente. La histología, estadio clínico y riesgo alto fueron mayoritariamente tipo epitelial (42,8 %), PRETEXT II (50,0 %) y riesgo alto (67,8 %) respectivamente. La media de AFP al diagnóstico fue 1055712ng/ml y 9 pacientes alcanzaron RC. La SVAG y SVLE general a 19 años fue 33,1 % y 26,0 % respectivamente. Según su extensión, la SVAG y la SVLE para los pacientes de riesgo estándar y alto fueron 50,0 % y 25,4 % (p=0,148); y 50,0 % y 14,7 % (p=0,037) respectivamente. La SVAG y SVLE verificadas son menores a las reportadas en otros estudios. La SVLE según su extensión, presentó diferencia significativa, sin embargo, este resultado debe ser tomado con cautela debido al número pequeño de pacientes.

SUMMARY: Hepatoblastoma (HB), is a malignant neoplasm, which originates in the liver. Survival (SV) depends on the extent of disease progression. The objective of this study was to determine differences in overall SV (OS) and disease-free (DFS) in patients with HB, according to the extent of their disease. Case series with follow-up. Patients between 4 and 160 months of age treated at an oncology center in the Ecuadorian Andes (2000-2019) were included. The result variables were affected lobe, lung metastasis, vascular infiltration, PRETEXT stage, risk, histology, alpha-fetoprotein levels (AFP), complete remission (RC), OS and DFS. Descriptive and analytical statistics (Chi2, Fisher's exact and continuity correction) were used. SV analyzes were performed with Kaplan Meier and log-rank curves. In this analysis 28 patients (53.6 % men), with a median age of 40 months, were studied. Lung metastases and vascular infiltration were verified in 25.0 % and 35.7 % of the cases, respectively. Histology, clinical stage, and high risk were mainly epithelial type (42.8 %), PRETEXT II (50.0 %), and high risk (67.8 %), respectively. The mean AFP at diagnosis was 1055712 ng / ml and 9 patients achieved CR. OS and DFS at 19 years were 33.1 % and 26.0 % respectively. According to their extension, the OS and DFS for standard and high risk patients were 50.0 % and 25.4 % (p = 0.148); and 50.0 % and 14.7 % (p = 0.037) respectively. The verified OS and DFS are lower than those reported in other studies. DFS according to its extension, presented a significant difference, however, this result should be considered with caution due to the small number of patients.

Hepatectomía central combinada con ligadura de la vena porta derecha en un niño con hepatoblastoma bilobar: reporte de un caso / Central hepatectomy combined with ligation of the right portal vein in a child with bilobar hepatobastoma: a case report

Resumen El hepatoblastoma es un tumor maligno, la resección quirúrgica es la meta del tratamiento. Paciente de 7 meses de edad con masa hepática en los segmentos IV A y B, V y VIII, clasificada como PRETEXT III, se realizó hepatectomía central conservando segmentos VI, VII, II, III y doble derivación biliodigestiva. La vena porta derecha involucrada, se ligó para producir hiperplasia compensadora izquierda, conservando el derecho como auxiliar. Hígado izquierdo en 14 días aumentó 48.1 %. Como alternativa al trasplante, en un tiempo quirúrgico se combinó hepatectomía central con ligadura de la vena porta derecha.

Abstract Hepatoblastoma is a malignant tumor. Surgical resection is the goal of treatment. A 7-month-old female patient with a hepatic mass in segments IV A and B, V, and VIII, classified as PRETEXT III. A central hepatectomy preserving segments VI, VII, II, and III, and a double biliodigestive derivation were performed. The right portal vein involved was ligated to produce a compensatory hyperplasia of the left liver, retaining the right one as an auxiliary. At 14 days, the left liver had increased by 48.1%. As an alternative to transplantation, central hepatectomy was combined with ligation of the right portal vein in a single surgical time.

Hepatoblastoma del adulto: presentación de un caso / A case of adult hepatoblastoma

Resumen Fundamento: el hepatoblastoma del adulto (HBA) es un tumor hepático poco frecuente y con un mal pronóstico, lo cual contrasta con el hepatoblastoma infantil (HBI). Esta patología aún no ha sido comprendida completamente y hasta la fecha, no se han reportado de forma adecuada más de 50 casos en la literatura médica. Objetivo: presentar el caso de un paciente que fue egresado de nuestro hospital con el diagnóstico de carcinoma hepatocelular, aproximadamente con 3 meses de anterioridad. Caso clínico: paciente masculino de 60 años con historia de alcoholismo y de ser un fumador inveterado. Fue ingresado en nuestro hospital por dolor abdominal, en el momento del examen físico, puso de manifiesto un tumor palpable en la región del hipocondrio derecho. Este paciente había sido egresado aproximadamente 3 meses atrás, con el diagnóstico de carcinoma hepatocelular, en el curso de una cirrosis hepática. El hombre falleció por causa de la progresión de la enfermedad y la autopsia reveló la existencia de un HBA. Conclusiones : el HBA es un tumor infrecuente, de grave pronóstico y muchos casos son asintomáticos hasta el momento del diagnóstico. Dicho tumor, por lo regular, presenta un gran tamaño. Las enzimas hepáticas, la alfafetoproteína y los estudios imagenológicos revelan el diagnóstico de un hepatocarcinoma, el cual es un tumor frecuente en los adultos. Asimismo, el estudio histológico confirma el diagnóstico. Debido a su mal pronóstico, y a las mejores perspectivas de tratamiento en niños, hoy en día es lógico utilizar el tratamiento pediátrico en los adultos. Se necesitan más estudios de investigación para el manejo óptimo del HBA.

Abstract Background: In contrast to childhood hepatoblastoma, adult hepatoblastoma (HBA) is a rare and not-fully-understood liver tumor with a poor prognosis. To date, about 50 cases have been adequately reported in the medical literature. Objective: We present the case of a patient who was discharged from our hospital with a diagnosis of hepatocellular carcinoma approximately 3 months before returning. Clinical case: A 60-year-old male patient with a history of alcoholism and heavy smoking was admitted to our hospital for abdominal pain. Physical examination revealed a palpable tumor in the right hypochondrium region. This patient had been discharged approximately 3 months previously with a diagnosis of hepatocellular carcinoma in the course of liver cirrhosis. The patient died, and the autopsy revealed an HBA. Conclusions: Adult hepatoblastoma is an infrequent tumor with a severe prognosis. Many cases are asymptomatic until the time of diagnosis, and the tumor is usually very large. Liver enzymes, alpha-fetus protein, and imaging studies lead to a diagnosis of hepatocellular carcinoma which is a common tumor in adults. Histological study confirms the diagnosis. Due to the poor prognosis for HBA in contrast to better prospects for treatment of hepatoblastoma in children, it is logical to use pediatric treatment in adults. More research is needed for the optimal treatment of HBA.

Therapeutic effect and clinical cost of multi-disciplinary team model of hepatoblastoma in children / 北京大学学报(医学版)

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.

Estudo genômico do tumor embrionário hepatoblastoma / Genomic study of the embryonal tumor hepatoblastoma

O hepatoblastoma, câncer de fígado mais comum na infância, é um tumor embrionário que se supõe surgir da interrupção da diferenciação hepática durante a embriogênese. O genoma deste tipo tumoral carrega poucas alterações somáticas, principalmente aneuploidias cromossômicas e mutações em CTNNB1. Essa relativa escassez de mutações somáticas representa um desafio à estratificação de risco dos pacientes e ao desenvolvimento de terapias direcionadas. Neste trabalho, investigamos por sequenciamento de exoma o espectro de mutações somáticas em um grupo de 10 hepatoblastomas, pareados com suas respectivas amostras germinativas, incluindo um caso de tumor congênito. Os dados genômicos revelaram que os hepatoblastomas tem número reduzido de mutações somáticas codificadoras não-sinônimas (média de ~6 variantes/tumor, com exclusão do caso congênito), totalizando 94 mutações (92 diferentes) nos 10 tumores, mapeadas em 87 genes. Apenas três genes apresentaram mutações detectadas em mais de uma amostra, CTNNB1, CX3CL1 e CEP164. As mutações foram validadas pelo sequenciamento de um painel composto pelos genes identificados no exoma, também utilizado para investigar estes genes em um grupo adicional de 12 tumores; apenas mutações em CTNNB1 foram detectadas neste grupo adicional. Mutações somáticas em CTNNB1 foram detectadas em ~54% do grupo estudado (22 hepatoblastomas): sete variantes patogênicas do tipo nucleotídeo único (SNV) ou indel foram identificadas em oito hepatoblastomas (~36%), uma delas nunca previamente descrita (A21_S33del); deleções intragênicas foram detectadas por sequenciamento Sanger em quatro outros tumores (~18%). A proteína ß-catenina foi avaliada por imunohistoquímica, apresentando translocação para o núcleo, o que indica ativação da via WNT; esse resultado também foi observado em tumores nos quais mutações em CTNNB1 não foram detectadas. O principal achado do estudo do exoma de hepatoblastomas foi a identificação de uma mutação somática recorrente no éxon 3 do gene CX3CL1 (A235G), observada em dois diferentes tumores. A análise de expressão gênica e proteica de CX3CL1 e de seu receptor CX3CR1 revelou aumento de expressão de CX3CL1 em hepatoblastomas; este resultado foi replicado em duas coortes independentes. O detalhamento da análise evidenciou um padrão bimodal: (a) linfócitos infiltrados em regiões tumorais de inflamação pós-quimioterapia eram negativos para essas proteínas, que deveriam estar expressas neste tipo celular em condições normais, enquanto as células tumorais as expressavam; (b) nas áreas de necrose tumoral pós-quimioterapia, houve detecção das proteínas CX3CL1/CX3CR1 nos linfócitos, mas não nas células tumorais. Em conjunto, estes resultados sugerem que a ativação da via CX3CL1/CX3CR1 ocorre em parte dos hepatoblastomas, independentemente da detecção de mutações, o que parece ser um achado relevante, potencialmente relacionado a inflamação e/ou resistência à quimioterapia. Adicionalmente, três assinaturas mutacionais foram detectadas nos hepatoblastomas, duas delas com predomínio das assinaturas do COSMIC, HB-S1 (COSMIC 1 e 6, presentes em todos os tipos de câncer) e HB-S2, com similaridades à assinatura COSMIC 29, relacionada apenas a carcinoma oral de células escamosas (gengivo-bucal) associado ao hábito de mascar tabaco; uma nova assinatura mutacional foi observada em um subconjunto de hepatoblastomas (HB-S3), com padrão inespecífico de pequeno aumento de mutações C>A. As assinaturas mutacionais já relatadas para câncer de fígado não foram evidentes nestes hepatoblastomas, sugerindo um processo mutacional diferente em sua origem. Por fim, análise de mutações germinativas no caso de hepatoblastoma congênito levou à identificação de variantes germinativas em genes de predisposição a câncer (BRCA1 e FAH), levantando a questão do papel da predisposição genética no desenvolvimento destes tumores embrionários (AU)

Hepatoblastoma, the most common liver cancer in infancy, is an embryonal tumor supposed to arise from differentiation impairment during embryogenesis. Hepatoblastomas genomes carry few somatic changes, mainly chromosomal aneuploidies and mutations in the CTNNB1 gene. This relative paucity of somatic mutations poses a challenge to risk stratification and development of targeted therapies. In this work, we investigated the burden of somatic mutations in a cohort of 10 hepatoblastomas paired with their respective germline samples, including a case of congenital tumor. Data revealed a low number of non-synonymous somatic coding mutations (mean of ~6 variants/tumor), totalizing 94 mutations in the 10 tumors, mapped in 87 genes; only three genes exhibited mutations detected in more than one sample, CTNNB1, CX3CL1 and CEP164. Target sequencing was used for validation and screening of the mutated genes in an additional group of 12 tumors; only CTNNB1 mutations were detected in this additional group. CTNNB1 mutations were detected in ~54% of the cohort (22 hepatoblastomas): seven single nucleotide variant or indel mutations were identified in eight hepatoblastomas (~36%), including the A21_S33del mutation, not previously reported; intragenic deletions were detected by Sanger sequencing in 4 tumors (~18%). The ß-catenin protein was evaluated by immunohistochemistry, presenting translocation to the nucleus, indicating activation of the WNT pathway; this result was also observed in tumors without CTNNB1 mutations. The main finding of the exome study was the identification of a recurrent somatic mutation in the exon 3 of the CX3CL1 gene (A235G) in two different hepatoblastomas. Gene expression and protein analysis of CX3CL1 and its receptor CX3CR1 revealed increased expression of CX3CL1 in hepatoblastomas, a result that was replicated in two independent cohorts. A bimodal pattern of expression was observed: (a) lymphocytes infiltrated in tumor regions of inflammation post-chemotherapy were negative for these proteins, which should be expressed in this cell type under normal conditions, while the tumor cells expressed them; (b) in areas of tumor necrosis after chemotherapy, CX3CL1/CX3CR1 proteins were detected in lymphocytes, but not in tumor cells. Taken together, these results suggest that activation of the CX3CL1/CX3CR1 pathway occurs in part of the hepatoblastomas, regardless of mutation detection, potentially related to inflammation and/or resistance to chemotherapy. Additionally, three mutational signatures were detected, two of them with a predominance of signatures of COSMIC, HB-S1 (COSMIC 1 and 6, present in all types of cancer) and HB-S2 (COSMIC 29 signature, related only to oral cell carcinoma gingival-buccal associated with the habit of chewing tobacco). A new mutational signature was observed in a subset of hepatoblastomas (HB-S3), with a non-specific pattern of small increase in C>A mutations. Mutational signatures already reported for liver cancer were not evident in these hepatoblastomas, suggesting a different mutational process. Finally, an exploration of germline mutations in the congenital hepatoblastoma led to the identification of variants in genes of cancer predisposition (BRCA1 and FAH), raising the question of the role of genetic predisposition in the development of these embryonal tumors (AU)

A Case of Congenital Hepatoblastoma Presented with Hepatic Osteodystrophy Complicated by Multiple Bone Fractures / 임상소아혈액종양

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.

Adrenal Cortical Neoplasm with Uncertain Malignant Potential Arising in the Heterotopic Adrenal Cortex in the Liver of a Patient with Beckwith-Wiedemann Syndrome

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.

Chronic Gastric Volvulus as a Late Complication of Hepatectomy for Hepatoblastoma in a Child: A Case Report / 대한소아소화기영양학회지

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.

Two Pediatric Cases of Spontaneous Ruptured Solid Tumors Successfully Treated with Transcutaneous Arterial Embolization / 임상소아혈액종양

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.

Metástases pulmonares em crianças: estamos operando desnecessariamente? / Pulmonary metastases in children: are we operating unnecessarily?

RESUMO Objetivo: determinar, em pacientes pediátricos portadores de neoplasias malignas, as características de nódulos pulmonares identificados à tomografia computadorizada, capazes de diferenciar nódulos benignos de metástases. Métodos: estudo retrospectivo de pacientes submetidos a ressecções pulmonares de nódulos diagnosticados como metástases em um período de sete anos. Achados de tomografia e da cirurgia, assim como resultados dos exames anatomopatológicos foram comparados. Resultados: nove pacientes, submetidos a 11 intervenções cirúrgicas, foram estudados. Entre as variáveis estudadas, apenas o tamanho do nódulo, maior do que 12,5mm provou ser estatisticamente significante para predizer malignidade. Conclusão: esse estudo sugere que, entre as características tomográficas de nódulos pulmonares de crianças portadoras de neoplasias malignas, apenas o tamanho da lesão foi preditor de malignidade.

ABSTRACT Objective: to determine, in pediatric patients with malignant neoplasms, the characteristics of pulmonary nodules identified on computed tomography, as well as the possibility of differentiating benign lesions from metastases. Methods: we conducted a retrospective study of patients submitted to pulmonary resections of nodules diagnosed as metastases in a period of seven years. We compared computed tomography and surgery findings, as well as results of anatomopathological examinations. Results: we studied nine patients submitted to 11 surgical interventions. Among the studied variables, only nodule size greater than 12.5mm proved to be statistically significant to predict malignancy. Conclusion: among the tomographic characteristics of pulmonary nodules in children with malignant neoplasms, only the size of the lesion was a predictor of malignancy.

Clinical Implication of Surgically treated Abdominoperineal Soild Tumor in the Newborn : A Single-Center Experience

PURPOSE: Abdominoperineal solid tumors presenting in neonates often require surgical intervention during the neonatal period. Although we report our single-center experience, this study would be meaningful to understand the clinical implications of these neoplasms. METHODS: We retrospectively reviewed and analyzed the clinical data and characteristics of 22 patients (≤28 days old) diagnosed with histopathologically confirmed abdominoperineal solid neoplasms (benign or malignant) after surgical resection. RESULTS: The mean gestational age and postnatal age at the time of operation were 38.3±1.8 weeks and 13.5±8.3 days, respectively. Most patients (18/22, 81.8%) were diagnosed during antenatal care visits; however, 4 (18.2%) were identified after birth. The mean tumor size was 6.4×5.3 cm (3.5–17.0 cm), and tumors occurred most frequently within the sacrococcygeal region (8/22, 36.4%). Histopathologically, 14 patients (63.6%) demonstrated benign tumors and 8 (36.4%) demonstrated malignant tumors. Germ cell tumors and hepatoblastomas were the most commonly observed tumors. Fortunately, all patients showed a localized pattern of tumor involvement without distant metastasis. No recurrence or mortality was observed during the follow-up period (mean 66.4±44.2 months). CONCLUSION: Abdominoperineal solid tumors occurring in neonates show variable clinical patterns during the antenatal and postnatal monitoring/screening periods. We conclude that aggressive and multidisciplinary approaches could achieve good clinical results in these patients.

Series de Pediatría Garrahan. El niño con cáncer / Garrahan Pediatrics Series. The child with cancer

La sobrevida de los niños con enfermedades oncológicas ha aumentado de manera considerable en las últimas décadas y este logro se alcanzó, entre otros factores, gracias a la detección temprana de la patología, los avances en los métodos diagnósticos, la administración de terapéuticas específicas adaptadas al riesgo y la adecuada implementación de medidas de soporte. Sin embargo, el cuidado de estos pacientes sigue representando un difícil desafío y requiere la conformación de equipos en los que el pediatra cumple un rol fundamental en la atención conjunta con el oncólogo y en la coordinación de la intervención de los demás especialistas. Este nuevo volumen aborda esta interesante temática y entre sus características destacadas se encuentran: El estudio de importantes temas, como la prevención del cáncer en pediatría en el mundo y en la Argentina, y la necesidad de construir programas de integración, educación e investigación en el cáncer pediátrico; el niño con una masa abdominal, con sus estrategias diagnósticas y las eventuales urgencias metabólicas, infectológicas y nutricionales durante el período de inducción, y cómo anticiparlas y prevenirlas; las situaciones clínicas de riesgo, como la compresión medular, el síndrome de vena cava superior y las complicaciones asociadas con la utilización de irinotecán; los aspectos ginecológicos en las niñas con cáncer, como las conductas frente al riesgo de sangrado menstrual durante el período de inducción, la actividad sexual y el embarazo durante el tratamiento, y la preservación de la fertilidad; y la leucemia linfoblástica aguda en etapa de reinducción, período especialmente significativo por la elevada morbilidad y las dificultades en el soporte clínico que requieren estos pacientes. La inclusión en todos los capítulos de casos clínicos ejemplificadores con su evolución y desenlace, textos destacados con los conceptos más importantes y puntos clave para recordar. Una obra sólida y práctica, que transmite la experiencia de los profesionales de una institución del prestigio internacional del Hospital de Pediatría Prof. Dr. Juan P. Garrahan, dedicada a todos los pediatras dondequiera que trabajen al servicio de los niños.

The genetic and epigenetic landscapes of hepatoblastomas

Primary liver cancers are rare in children, and the most common type is hepatoblastoma (HB), an embryonal tumor with histological features that resemble different stages of liver cell differentiation. However, mainly because of its rarity, molecular data on HB tumorigenesis remain scarce. This article reviews the current knowledge regarding genetic and epigenetic alterations reported in HB cases, with emphasis on the recent findings of next-generation sequencing studies (AU)

False Positive Diagnosis of Hepatocellular Carcinoma in Liver Resection Patients

The diagnosis of hepatocellular carcinoma (HCC) is based on imaging studies particularly in high-risk patients without histologic confirmation. This study evaluated the prevalence and characteristics of false-positively diagnosed HCC in a liver resection cohort for HCC. A retrospective review was performed of 837 liver resection cases for clinically diagnosed HCC between 2005 and 2010 at our institute. High-risk patients with tumors > 1 cm with one or two image findings consistent with HCC and tumors 0.05) compared to non-HCC patients except for higher rate of history of alcoholism (P < 0.05) observed in non-HCC patients. Four of 18 non-HCC patients (22.2%) showed diagnostic discordance on the dynamic imaging study. Despite the recent progression in diagnostic imaging techniques, 2.2% of cases were false-positively diagnosed as HCC in a liver resection patient cohort; and the final diagnosis was benign disease in 0.8% of liver resection patients clinically diagnosed with HCC.

Hirschsprung disease and hepatoblastoma: case report of a rare association / Doença de Hirschsprung e hepatoblastoma: relato de caso de uma associação rara

ABSTRACT CONTEXT: Hirschsprung disease is a developmental disorder of the enteric nervous system that is characterized by absence of ganglion cells in the distal intestine, and it occurs in approximately 1 in every 500,000 live births. Hepatoblastoma is a malignant liver neoplasm that usually occurs in children aged 6 months to 3 years, with a prevalence of 0.54 cases per 100,000. CASE REPORT: A boy diagnosed with intestinal atresia in the first week of life progressed to a diagnosis of comorbid Hirschsprung disease. Congenital cataracts and sensorineural deafness were diagnosed. A liver mass developed and was subsequently confirmed to be a hepatoblastoma, which was treated by means of surgical resection of 70% of the liver volume and neoadjuvant chemotherapy (ifosfamide, cisplatin and doxorubicin). CONCLUSION: It is known that Hirschsprung disease may be associated with syndromes predisposing towards cancer, and that hepatoblastoma may also be associated with certain congenital syndromes. However, co-occurrence of hepatoblastoma and Hirschsprung disease has not been previously described. We have reported a case of a male patient born with ileal atresia, Hirschsprung disease and bilateral congenital cataract who was later diagnosed with hepatoblastoma.

RESUMO CONTEXTO: A doença de Hirschsprung é uma desordem do desenvolvimento do sistema nervoso entérico, que é caracterizada pela ausência de células ganglionares no intestino distal, ocorrendo em cerca de 1 a cada 500.000 nascimentos. O hepatoblastoma é uma neoplasia maligna do fígado que geralmente ocorre em crianças de 6 meses a 3 anos, com prevalência de 0,54 casos por 100.000. RELATO DE CASO: Um menino com diagnóstico de atresia intestinal na primeira semana de vida evoluiu com diagnóstico concomitante de doença de Hirschsprung. Catarata congênita e surdez neurossensorial foram diagnosticadas. Surgiu lesão hepática com posterior confirmação de hepatoblastoma, tratado com ressecção cirúrgica de 70% do volume hepático e quimioterapia neoadjuvante (ifosfamida, cisplatina e doxorubicina). CONCLUSÃO: Sabe-se que a doença de Hirschsprung pode estar associada a síndromes de predisposição ao câncer, da mesma forma que o hepatoblastoma já foi correlacionado a certas síndromes congênitas malformativas. No entanto, até o momento, a associação de hepatoblastoma com a doença de Hirschsprung não foi descrita. Relatamos o caso de um menino que nasceu com atresia ileal, doença de Hirschsprung, catarata congênita bilateral e com posterior diagnóstico de hepatoblastoma.

Screening and identification of apolipoprotein A-I as a potential marker for hepatoblastoma in children / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To screen and identify serum biomarkers for childhood hepatoblastoma (HB).</p><p><b>METHODS</b>The serum samples from 30 children with hepatoblastoma (HB), 20 children with systemic inflammatory response syndrome, and 20 normal children were treated with magnetic bead-based weak cation exchange chromatography. The platform of surface-enhanced laser desorption/ionization-time of flight-mass spectrometry (SELDI-TOF-MS) was used to eliminate the interference of inflammatory factors and to screen out the differentially expressed proteins in serum between tumor group and normal group. After the purification and separation of target proteins were performed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, matrix-assisted laser desorption/ionization-time of flight-mass spectrometry was used to determine their amino acid sequences. The SwissProt database was searched for matched proteins. Finally, real-time PCR and ELISA were used to verify and measure the expression of target proteins.</p><p><b>RESULTS</b>After SELDI-TOF-MS was used for screening and elimination of the interference of inflammatory factors, a differentially expression protein with a mass-to-charge ratio of 9 348 Da was found in serum between HB group and normal group, and the HB group had significantly lower expression of this protein than the normal group (p<0.05). This protein was identified as apolipoprotein A-1 (Apo A-I). Real-time PCR and ELISA verified the low mRNA and protein expression of Apo A-I in serum in the HB group and high expression in serum in the normal group.</p><p><b>CONCLUSIONS</b>Apo A-I can be used as a non-inflammatory protein marker for HB and has a certain value in the early diagnosis of HB.</p>

New concepts and outcomes for children with hepatoblastoma based on the experience of a tertiary center over the last 21 years

OBJECTIVE: The aim of this study was to summarize the experience of a tertiary center in treating hepatoblastoma for the last 21 years. PATIENTS AND METHODS: Fifty-eight cases were included. The tumor extent and prognosis were assessed using the PRETEXT system. The following data were analyzed: age at diagnosis, comorbidities, prematurity, treatment modalities, histopathological findings, surgical details and complications, treatment outcomes, chemotherapy schedules, side effects and complications. Treatment outcomes included the occurrence of local or distant recurrence, the duration of survival and the cause of death. The investigation methods were ultrasonography, CT scan, serum alpha-fetoprotein level measurement and needle biopsy. Chemotherapy was then planned, and the resectability of the tumor was reevaluated via another CT scan. RESULTS: The mean numbers of neoadjuvant cycles and postoperative cycles of chemotherapy were 6±2 and 1.5±1.7, respectively. All children except one were submitted for surgical resection, including 50 partial liver resections and 7 liver transplantations. Statistical comparisons demonstrated that long-term survival was associated with the absence of metastasis (p=0.04) and the type of surgery (resection resulted in a better outcome than transplantation) (p=0.009). No associations were found between vascular invasion, incomplete resection, histological subtype, multicentricity and survival. The overall 5-year survival rate of the operated cases was 87.7%. CONCLUSION: In conclusion, the experience of a Brazilian tertiary center in the management of hepatoblastoma in children demonstrates that long survival is associated with the absence of metastasis and the type of surgery. A multidisciplinary treatment involving chemotherapy, surgical resection and liver transplantation (including transplantations using tissue from living donors) led to good outcomes and survival indexes. .

Recent Update in Hepatoblastoma / 임상소아혈액종양

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.