Association of Sociodemographic Factors with Surgical Management of Hepatoblastoma and Hepatocellular Carcinoma in Children.

OBJECTIVE: To evaluate for disparities in surgical care among US children with hepatoblastoma (HB) and hepatocellular carcinoma (HCC). STUDY DESIGN: In this retrospective National Cancer Database study (2004-2015), children aged <18 years with HB or HCC were included. Multivariable mixed-effects logistic regression was used to evaluate the association of sociodemographic factors (age, sex, race and ethnicity, insurance status, income, proximity to treating hospital) with the odds of undergoing surgical treatment after adjusting for disease-related factors (tumor size, metastasis, comorbidities) and hospital-level effects. Subgroup analyses by tumor histology were performed. RESULTS: A total of 811 children were included (HB: 80.9%; HCC: 19.1%), of which 610 (75.2%) underwent surgical treatment. Following adjustment, decreased odds of undergoing surgical treatment were associated with Black race (OR: 0.46 vs White, 95% CI [95% CI]: 0.26-0.80, P = .01), and having Medicaid (OR: 0.58 vs private, 95% CI: 0.38-0.88, P = .01) or no insurance (OR: 0.33 vs private, 95% CI: 0.13-0.80, P = .02). In children with HB, Black race was associated with decreased odds of undergoing surgical treatment (OR: 0.47 vs White, 95% CI: 0.25-0.89, P = .02). In children with HCC, Medicaid (OR: 0.10 vs private, 95% CI: 0.03-0.35, P < .001), or no insurance status (OR: 0.10 vs private, 95% CI: 0.01-0.83, P = .03) were associated with decreased odds of undergoing surgical treatment. Other than metastatic disease, no additional factors were associated with likelihood of surgical treatment in any group. CONCLUSIONS: Black race and having Medicaid or no insurance are independently associated with decreased odds of surgical treatment in children with HB and HCC, respectively. These children may be less likely to undergo curative surgery for their liver cancer.

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.

Glomerular filtration rate in liver transplant for unresectable hepatoblastoma.

Most children with hepatoblastoma manifest, at the time of LT, a decrease in renal function due to chemotherapy that could be further deteriorated by the use of calcineurin inhibitors. The purpose of this work was to examine the long-term follow-up of renal function in a cohort of children transplanted for unresectable hepatoblastoma. We present a retrospective observational study of 10 pediatric patients who received a LT for unresectable hepatoblastoma between 1996 and 2016. All patients included in this study were followed up on a regular basis and were assessed for GFR before transplantation and at least once a year during follow-up. All patients received standardized chemotherapy treatment for hepatoblastoma and immunosuppression according to hospital protocols. There was a marked decrease in GFR at the time of the LT in five patients presenting renal complications during the pretransplant cycles of chemotherapy. Three patients, one of them with prior kidney involvement, presented complications after LT, namely acute kidney failure and decrease in GFR. Those patients who presented with the lowest GFR at the time of LT eventually recovered renal function at levels similar to the rest of the group on follow-up. Chemotherapy-induced nephrotoxicity is a concern in patients treated for hepatoblastoma. Some individuals will develop low GFR after chemotherapy; therefore, strict follow-up is recommended, as low GFR may affect the doses of subsequent chemotherapy and immunosuppression. Stabilization of GFR levels and occasional improvement can be observed in the post-transplant period.

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 16 000 ng/dL, with a sensitivity of 71.43% and a specificity of 85.71%. Multivariate analysis showed that patients with higher values of pretransplant AFP (>16 000 ng/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.

Extensive Hepatectomy as an Alternative to Liver Transplant in Advanced Hepatoblastoma: A New Protocol Used in a Pediatric Liver Transplantation Center.

BACKGROUND: Surgery is a key factor in the treatment of hepatoblastoma, but choosing between an aggressive resection and liver transplant may be an extremely difficult task. The aim of this study was to describe the outcomes of patients with advanced hepatoblastoma: pretreatment extent of disease (PRETEXT)/post-treatment extent of disease (POST-TEXT) III and IV undergoing aggressive resections or living donor liver transplant in cases involving the entire liver. Based on this experience, a new protocol for the treatment of these patients was proposed. METHODS: A retrospective study included patients with advanced hepatoblastoma (POST-TEXT III and IV) who were referred for a liver transplant from 2010 to 2017. RESULTS: A total of 24 children were included: 13 (54.2%) were male, with a median age at diagnosis of 42 months (range, 15-120 months), and a history of prematurity was identified in 20.8% of the patients. Ten cases (41.7%) were staged as PRETEXT/POST-TEXT III, and 12 cases (50.0%) were staged as PRETEXT/POST-TEXT IV. Two patients were referred after posthepatectomy recurrence. Five patients underwent a liver transplant, with recurrence and death in 2 patients (40.0%) within a mean period of 6 months. In the extensive hepatectomy group, there was recurrence in 6 patients (31.6%), with disease-free outcomes and overall survival in 63.2% and 94.7% of patients, respectively. CONCLUSION: In cases of advanced hepatoblastoma, an extensive surgical approach is a valuable option. The fact that the team was fully prepared to proceed with living donor liver transplant allowed the surgeon to be more aggressive and to switch to transplantation when resection was not possible.

Clear cell hepatocellular carcinoma arising 25 years after the successful treatment of an infantile hepatoblastoma.

Primary liver tumors in children are rare with hepatoblastoma (HB) being the most common malignancy. Clear cell carcinoma, a variant of hepatocellular carcinoma (HCC), is another rare tumor of the liver that tends to affect adults. We describe the diagnosis and management of the only known documented case of a primary clear cell HCC arising twenty-five years after the patient was successfully treated with chemotherapy and surgical resection for a malignant HB as an infant. While some evidence has shown a genetic link between HB and various types of HCC, other research has shown distinct chromosomal alterations and molecular mechanisms unique to both. Further knowledge of liver tumorigenesis will help elucidate the complicated genetic, molecular, and environmental factors involved in the development of these two rare hepatic malignancies.

Surgical treatment of hepatic tumors in children: lessons learned from liver transplantation.

PURPOSE: Hepatectomy remains a complex operation even in experienced hands. The objective of the present study was to describe our experience in liver resections, in the light of liver transplantation, emphasizing the indications for surgery, surgical techniques, complications, and results. METHODS: The medical records of 53 children who underwent liver resection for primary or metastatic hepatic tumors were reviewed. Ultrasonography, computed tomographic (CT) scan, and needle biopsy were the initial methods used to diagnose malignant tumors. After neoadjuvant chemotherapy, tumor resectability was evaluated by another CT scan. Surgery was performed by surgeons competent in liver transplantation. As in liver living donor operation, vascular anomalies were investigated. The main arterial anomalies found were the right hepatic artery emerging from the superior mesenteric artery and left hepatic artery from left gastric artery. Hilar structures were dissected very close to liver parenchyma. The hepatic artery and portal vein were dissected and ligated near their entrance to the liver parenchyma to avoid damaging the hilar vessels of the other lobe. During dissection of the suprahepatic veins, the venous infusion was decreased to reduce central venous pressure and potential bleeding from hepatic veins and the vena cava. RESULTS: Fifty-three children with hepatic tumors underwent surgical treatment, 47 patients underwent liver resections, and in 6 cases, liver transplantation was performed because the tumor was considered unresectable. There were 31 cases of hepatoblastoma, with a 9.6% mortality rate. Ten children presented with other malignant tumors-3 undifferentiated sarcomas, 2 hepatocellular carcinomas, 2 fibrolamellar hepatocellular carcinomas, a rhabdomyosarcoma, an immature ovarian teratoma, and a single neuroblastoma. These cases had a 50% mortality rate. Six children had benign tumors-4 mesenchymal hamartoma, 1 focal nodular hyperplasia, and a mucinous cystadenoma. All of these children had a favorable outcome. Hepatic resections included 22 right lobectomies, 9 right trisegmentectomies, 8 left lobectomies, 5 left trisegmentectomies, 2 left segmentectomies, and 1 case of monosegment (segment IV) resection. The overall mortality rate was 14.9%, and all deaths were related to recurrence of malignant disease. The mortality rate of hepatoblastoma patients was less than other malignant tumors (P = .04). CONCLUSION: The resection of hepatic tumors in children requires expertise in pediatric surgical practice, and many lessons learned from liver transplantation can be applied to hepatectomies. The present series showed no mortality directly related to the surgery and a low complication rate.

The current management of hepatoblastoma: a combination of chemotherapy, conventional resection, and liver transplantation.

OBJECTIVE: To review our experience in the management of children who present with hepatoblastoma. STUDY DESIGN: Thirty patients treated for hepatoblastoma at a single institution were reviewed. RESULTS: Ten patients presented with stage I to stage II disease and underwent resection. Seventeen presented with stage III disease; two underwent initial resection of which one required rescue transplantation. The remaining 15 underwent biopsies, which were followed by chemotherapy. Nine patients had a reduction in tumor size and underwent conventional resection. One required rescue transplantation for residual disease. Five patients underwent primary transplantation for unresectable disease. One patient expired during chemotherapy. Three patients presented with stage IV disease and underwent biopsies, which were followed by chemotherapy. One patient responded but required "rescue" transplantation after conventional resection. Seven patients underwent aggressive conventional resection (trisegmentectomy or central liver resection); three had positive surgical margins and underwent transplantation. One developed recurrent disease. Five-year survival was 82.5% +/- 7.1%. There was no operative mortality during surgical therapy. All transplant recipients were tumor free, but one died from lymphoma 7 years post-transplant. CONCLUSION: Chemotherapy may reduce tumor size, allowing for conventional resection. If aggressive resection is necessary or bi-lobar disease persists, primary transplantation is recommended.

Liver transplantation and chemotherapy for hepatoblastoma and hepatocellular cancer in childhood and adolescence.

OBJECTIVE: To describe our experience with total hepatectomy and liver transplantation as treatment for primary hepatoblastoma (HBL) and hepatocellular carcinoma (HCC) in children. STUDY DESIGN: A retrospective analysis of the perioperative course of 31 children with unresectable primary HBL (n = 12) and HCC (n = 19) who underwent transplantation between May 1989 and December 1998. Systemic (n = 18) and intraarterial (n = 7) neoadjuvant chemotherapy were administered; follow-up ranged from 1 to 185 months. RESULTS: For HBL, 1-year, 3-year, and 5-year posttransplantation survival rates were 92%, 92%, and 83%, respectively. Intravenous invasion, positive hilar lymph nodes, and contiguous spread did not have a significant adverse effect on outcome; distant metastasis was responsible for 2 deaths. Intraarterial chemotherapy was effective in all patients treated. For HCC, the overall 1-year, 3-year, and 5-year disease-free survival rates were 79%, 68%, and 63%, respectively. Vascular invasion, distant metastases, lymph node involvement, tumor size, and gender were significant risk factors for recurrence. Intraarterial chemotherapy was effective in 1 of 3 patients. Six patients died of recurrent HCC, and 3 deaths were unrelated to recurrent tumor. CONCLUSION: Liver transplantation for unresectable HBL and HCC can be curative. Risk factors for recurrence were significant only for HCC, with more advanced stages amenable to cure in the HBL group.

Manejo multidisciplinario de tumores hepáticos malignos en el niño: una experiencia nacional reciente / Multidisciplinary management of hepatic malignant tumors in children: report of 6 cases

Background: malignant hepatic tumors (Mht) are rare in children. Among them hepatoblastoma (HB) is the most common. Aim: to report the results of the multidisciplinary management in 6 consecutive children: five HB and one metastatic Wilms tumor (MWT). Patients and methods: the mean age of patients was 42 months. All HB patients had elevated serum alfafetoprotein (median 150,000 ng/ml). All patients received preoperative chemotherapy: HB patients received carboplatin/doxorrubicin alternating with cisplatin, and the MWT patient, vincristine alone. Surgery included two formal right and two formal left hepatectomies, one extensive central resection with partial left segmentectomy, and one lateral segmentectomy. Extracorporeal circulation was used in the child with atrial involvement. All patients received postoperative chemotherapy. Results: all tumors had variable regresion on preoperative chemotherapy. Complete resection with negative margins was achieved in all patients. The degree of tumor necrosis on histology ranged from 60 percent to 90 percent. Alfafetoprotein levels fell to under 10 ng/ml in all HB cases, one to three months after surgery. All patients survive free of disease at a median follow up of 19 months. Conclusion: a multidisciplinary approach including the well timed used of chemotherapy and surgery is highly effective in the management of pediatric malignant tumors

Hepatoblastoma: experiencia en el tratamiento de 20 niños / Hepatoblastoma: experience in the treatment of 20 children

Introducción: el hepatoblastoma es el principal tumor maligno primario del hígado en niños. El objetivo del presente trabajo es analizar el perfil clínico, tipo de cirugía, complicaciones postoperatorias y sobrevida libre de enfermedad de acuerdo a la modalidad quirúrgica empleada, en niños con hepatoblastoma. Material y métodos: se revisaron los expedientes de pacientes con hepatoblastoma atendidos entre enero de 1985 y diciembre de 1995. Se registraron edad, sexo, manifestaciones clínicas, exámenes de laboratorio, alfa-feto proteína pre y postoperatoria, estudios de gabinete, tipo de procedimiento quirúrgico, complicaciones trans y postoperatorias variedad histológica, estudio, tipo de quimioterapia y sobrevida libre de enfermedad. Resultados: se analizaron 20 pacientes de cuatro meses a 13 años de edad. La principal e invariable manifestación clínica fue una masa abdominal. En once pacientes se encontraron niveles de alfa-feto proteína entre 100-10,000 ng/mL. En 12 pacientes se practicó hemihepatectomía; en cuatro, trisegmentectomía y en el resto, biopsia incisional diagnóstica. Hubo sangrado masivo en cuatro pacientes durante el transoperatorio; ninguno falleció. Todos los pacientes en estadio IV fallecieron. El tipo de resección, completa o incompleta, no fue estadísticamente significativo (p=0.49) para la sobrevida; ésta fue 7/20 con un seguimiento de cuatro a 104 meses. Conclusiones: 1. los niveles de alfa-feto proteína son útiles para la viginalcia y el diagnóstico de pacientes con hepatoblastoma. 2. La mayor sobrevida ocurre en pacientes operados y que recibieron quimioterapia. 3. Un segundo abordaje quirúrgico es preferible después de la citorreducción con quimioterapia en pacientes con tumores muy voluminosos o multicéntricos. 4. La conducta actual para el tratamiento del hepatoblastoma debe ser cirugía más quimioterapia independientemente del estadio

[Epithelial hepatoblastomas in the adult]. / Hepatoblastomas epiteliales en el adulto.

Hepatoblastoma is the most frequent primary malignant liver neoplasm in childhood; in adults it is extremely rare and only 27 cases have been published. The prognosis of this neoplasm is poor because it is usually discovered late. Surgery, chemotherapy and liver transplantation have been tried with poor results. We present two adult patients who were diagnosed with an epithelial hepatoblastoma. The pathogenesis, histologic features and current management is reviewed.