A rare case of severe Ebstein's anomaly and hepatoblastoma in a neonate.

Primary liver tumours in neonates with single-ventricle palliation are exceedingly rare. We present the first reported case of neonatal hepatoblastoma with severe Ebstein's anomaly following Starnes procedure. The patient's postoperative course highlights the challenges and complications in simultaneous management of these diagnoses. Transition from shunted single-ventricle physiology to bidirectional cavopulmonary connection improved end-organ function, permitting more aggressive hepatic malignancy treatment.

Pediatric Hepatoblastoma After Neoadjuvant Chemotherapy: Diagnostic Performance of MR in Staging POSTTEXT and Vascular Involvement.

BACKGROUND: The assessment of resectability after neoadjuvant chemotherapy of hepatoblastoma is dependent on Post-Treatment EXTENT of Disease (POSTTEXT) staging and its annotation factors P (portal venous involvement) and V (hepatic venous/inferior vena cava [IVC] involvement), but MR performance in assessing them remains unclear. PURPOSE: To assess the diagnostic performance of contrast-enhanced MR imaging for preoperative POSTTEXT staging and diagnosing vascular involvement in terms of annotation factors P and V in pediatric hepatoblastoma following neoadjuvant chemotherapy. STUDY TYPE: Retrospective. SUBJECTS: Thirty-five consecutive patients (17 males, median age, 24 months; age range, 6-98 months) with proven hepatoblastoma underwent preoperative MR imaging following neoadjuvant chemotherapy. FIELD STRENGTH/SEQUENCE: 3.0 T; T2-weighted imaging (T2WI), T2WI with fat suppression, diffusion weighted imaging, radial stack-of-the-star/Cartesian 3D Dixon T1-weighted gradient echo imaging. ASSESSMENT: Three radiologists independently assessed the POSTTEXT stages and annotation factors P and V based on the 2017 PRE/POSTTEXT system. The sensitivities and specificities were calculated for 1) diagnosing each POSTTEXT stage; 2) discrimination of stages III and IV (advanced) from those stages I and II (non-advanced) hepatoblastomas; and 3) annotation factors P and V. The combination of pathologic findings and surgical records served as the reference standard. STATISTICAL TESTS: Sensitivity, specificity, Fleiss kappa test. RESULTS: The sensitivity and specificity ranges for discriminating advanced from non-advanced hepatoblastomas were 73.3%-80.0% and 80.0%-90.0%, respectively. For annotation factor P, they were 66.7%-100.0% and 90.6%, respectively. For factor V, they were 75.0% and 67.7%-83.9%, respectively. There was excellent, substantial, and moderate agreement on POSTTEXT staging (Fleiss kappa = 0.82), factors P (Fleiss kappa = 0.64), and factors V (Fleiss kappa = 0.60), respectively. DATA CONCLUSION: MR POSTTEXT provides reliable discrimination between advanced and non-advanced tumors, and MR has moderate to excellent specificity at identifying portal venous and hepatic venous/IVC involvement. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.

The effect of donor graft type on survival after liver transplantation for hepatoblastoma in children.

BACKGROUND: Liver transplantation (LT) is the only potentially curative option for children with unresectable hepatoblastoma (HBL). Although post-transplant outcomes have improved in the contemporary era, the impact of donor graft type on survival remains unclear. METHODS: Using the United Network for Organ Sharing database (02/2002-06/2021), demographics, clinical characteristics, and patient and graft survival were analyzed in children (<18 years) who underwent LT for HBL according to donor graft type. The Kaplan-Meier method, log-rank tests, and Cox regression modeling were used to evaluate the effect of whole, partial, and split deceased donor liver transplantation (DDLT) and living donor liver transplantation (LDLT) on patient and graft survival. RESULTS: A total of 590 pediatric HBL LT recipients (344 whole graft DDLT; 62 partial graft DDLT; 139 split graft DDLT; 45 LDLT) were included. During 2012-2021 the proportion of LDLTs for HBL decreased to about 5% compared with about 11% during 2002-2011. No significant differences were identified by donor graft type in either patient survival (log-rank test, p = .45) or graft survival (log-rank test, p = .69). The results remained similar during the 2002-2011 era, while during the 2012-2021 era, split graft DDLT was associated with decreased graft loss risk versus whole graft DDLT (hazard ratio: 0.48, 95% confidence interval: 0.23-0.99, p = .046) without any other significant between-group differences. CONCLUSIONS: Utilizing non-whole liver grafts can increase access to LT in children with unresectable HBL while ensuring favorable outcomes. LDLT is underutilized in children with HBL in the United States, and efforts to explore LDLT options should be undertaken.

Modern-era successful liver transplantation outcomes in children with hepatic undifferentiated embryonal sarcoma.

BACKGROUND: Hepatic undifferentiated embryonal sarcoma (HUES) is the third most common primary hepatic malignancy in children. If unresectable, liver transplantation (LT) is the only curative option. Historically, HUES LT outcomes were not favorable; however, modern-era data are lacking. We aimed to describe LT outcomes in children with HUES and compared with LT outcomes in children transplanted for hepatoblastoma (HBL) and non-malignancy indications. METHODS: Children 18 years or younger with HUES who underwent LT from 1987 to 2021 were identified from the Scientific Registry of Transplant Recipients database. Graft and patient survival were studied in HUES and LT recipients with HBL and non-malignancy indications using Kaplan-Meier analysis. Cox regression was used to compare patient and graft survival among groups, controlling for confounders. RESULTS: Twenty-one children with HUES underwent LT during the study period with a median age at LT of 10 years (IQR: 8-12 years). One and five-year patient survival for HUES recipients was not significantly different from that of recipients with HBL (p = .3) or non-malignancy diagnoses (p = .6). There were no deaths due to HUES recurrence. In multivariable Cox regression, HUES did not increase risk of either patient or graft loss as compared to HBL (HR 2.36, p = .2) or non-malignancy indications (HR 0.74, p = .7). CONCLUSION: LT outcomes are more favorable in patients with HUES than historically described, and similar to LT outcomes of patients with HBL and non-malignancy indications. Transplant should be considered for HUES patients with unresectable localized tumors.

Navigating relapsed hepatoblastoma: Predictive factors and surgical treatment strategy.

OBJECTIVE: Hepatoblastoma (HB) is the most common primary hepatic malignancy in childhood. Relapse occurs in more than 50% of high-risk patients with a high mortality due to ineffective salvage therapies. The purpose of this study is to identify risk factors for relapsed HB and predictors of survival in a single tertiary referral center. METHODS: A retrospective chart review showed 129 surgically treated HB patients from October 2004 to July 2020. Of the cohort, 22 patients presented with relapsed HB. Relapse was defined as re-appearance of malignancy after 4 weeks of normalized AFP and disappearance of all tumors on imaging. RESULTS: Patients with relapsed HB had a 5-year overall survival (OS) of 45.4% compared to 93.1% in those without relapse (p = 0.001). When comparing PRETEXT IV, microvascular invasion, metastatic disease, and age on multivariate logistic regression, only PRETEXT IV was an independent risk factor for relapsed HB with an OR of 2.39 (95% CI: 1.16-4.96; p = 0.019). Mixed epithelial and mesenchymal HB (12/19, 63.2%) was the most common histology of primary tumors while pure epithelial HB (13/15, 86.6%) was the most common relapsed histology. Combination of surgical and medical therapy for relapsed disease was predictive of survival with an HR of 16.3 (95% CI: 1.783-149.091; p = 0.013) compared to only chemotherapy. CONCLUSIONS: This study demonstrates that PRETEXT IV staging is an independent predictor of relapsed disease. The most common relapsed histology was epithelial, suggesting a potential selection or resistance of this component. Surgical resection is a critical component of multimodal therapy for relapsed HB.

Critical elements of pediatric liver cancer surgery.

The appropriate management of pediatric liver malignancies, primarily hepatoblastoma and hepatocellular carcinoma, requires an in depth understanding of contemporary preoperative risk stratification, experience with advanced hepatobiliary surgery, and a good relationship with one's local or regional liver transplant center. While chemotherapy regimens have become more effective, operative indications more well-defined, and overall survival improved, the complexity of liver surgery in small children provides ample opportunity for protocol violation, inadequate resection, and iatrogenic morbidity. These guidelines represent the distillation of contemporary literature and expert opinion as a means to provide a framework for preoperative planning and intraoperative decision-making for the pediatric surgeon.

Evaluating the clinical efficacy and limitations of indocyanine green fluorescence-guided surgery in childhood hepatoblastoma: A retrospective study.

BACKGROUND: Indocyanine green (ICG) fluorescence guided surgery has been used to treat childhood hepatoblastoma (HB), but the advantages and disadvantages of this technique have not been fully discussed. The purpose of this study is to summarize the experience and to explore the clinical value of this technique for children with HB. METHODS: 45 children with HB who underwent ICG fluorescence guided surgery (n = 22) and general surgery (n = 23) in our center from January 2020 to December 2022 were enrolled retrospectively. RESULTS: All the liver tumors in the ICG group showed hyperfluorescence, including total and partial fluorescent types. With the help of ICG navigation, minimally invasive surgery was performed in 3 cases. 18.2 % of cases with tumors could not be accurately identified under white light, but could be identified by fluorescence imaging. The fluorescent cutting lines of 59.1 % of cases were consistent with the safe cutting lines. In 36.4 % of cases, the fluorescence boundary was not clear because of tumor necrosis. In 36.4 % of cases, the fluorescence could not be detected on the inner edge of the tumors because of the depth. A total of 29 ICG (+) suspicious lesions were found during the operations, of which 5 were true positive lesions. CONCLUSION: ICG fluorescence guided surgery is safe and feasible in children with HB. This technique is helpful for locating tumors, determining margin and finding small lesions with negative imaging, especially in minimally invasive surgery. However, preoperative chemotherapy, tumor necrosis, tumor depth, and ICG administration impact the effect of fluorescence imaging.

Advances in pediatric liver transplantation from the pediatric surgeon's perspective.

Pediatric liver transplantation is a lifesaving state-of-the-art operation for children with various liver diseases, including cholestatic diseases, metabolic disorders, acute liver failure, and primary malignant liver tumors. Among these indications, transplantation for biliary atresia and hepatoblastoma is discussed in this review because pediatric surgeons are usually involved in their initial treatments. For biliary atresia, pediatric surgeons are advised to keep dissection of the hilar structures to a minimum during Kasai portoenterostomy in order to make total hepatectomy easier at transplantation. Early referral to a transplant team is recommended when worrisome signs of liver dysfunction, cirrhosis, portal hypertension and growth retardation are noted. Hepatoblastoma with multiplicity or located close to major vessels may indicate unresectability, and the transplant team needs to be consulted early after neoadjuvant chemotherapy is started. The graft size, including its thickness, needs to be evaluated before transplantation for small children, as tailoring the shape of the partial graft may be necessary during the transplant procedure.

Surgical Management and Outcomes of Patients with Multifocal Hepatoblastoma.

OBJECTIVE: To compare the outcomes of patients with multifocal hepatoblastoma (HB) treated at our institution with either orthotopic liver transplant (OLTx) or hepatic resection to determine outcomes and risk factors for recurrence. BACKGROUND: Multifocality in HB has been shown to be a significant prognostic factor for recurrence and worse outcome. The surgical management of this type of disease is complex and primarily involves OLTx to avoid leaving behind microscopic foci of disease in the remnant liver. METHODS: We performed a retrospective chart review on all patients <18 years of age with multifocal HB treated at our institution between 2000 and 2021. Patient demographics, operative procedure, post-operative course, pathological data, laboratory values, short- and long-term outcomes were analyzed. RESULTS: A total of 41 patients were identified as having complete radiologic and pathologic inclusion criteria. Twenty-three (56.1%) underwent OLTx and 18 (43.9%) underwent partial hepatectomy. Median length of follow-up across all patients was 3.1 years (IQR 1.1-6.6 years). Cohorts were similar in rates of PRETEXT designation status identified on standardized imaging re-review (p = .22). Three-year overall survival (OS) estimate was 76.8% (95% CI: 60.0%-87.3%). There was no difference in rates of recurrence or overall survival in patients who underwent either resection or OLTx (p = .54 and p = .92 respectively). Older patients (>72 months), patients with a positive porta hepatis margin, and patients with associated tumor thrombus experienced worse recurrence rates and survival. Histopathology demonstrating pleomorphic features independently associated with worse rates of recurrence. CONCLUSIONS: Through proper patient selection, multifocal HB was adequately treated with either partial hepatectomy or OLTx with comparable outcome results. HB with pleomorphic features, increased patient age at diagnosis, involved porta hepatis margin on pathology, and the presence of associated tumor thrombus may be associated with worse outcomes regardless of the local control surgery offered. LEVEL OF EVIDENCE: III.

A rare case report of extrahepatic hepatoblastoma in a child.

Hepatic malignancies account for 1-4% of all childhood solid tumours and Hepatoblastoma is the most common malignant liver tumour in children. Its extrahepatic origin is rare. Here we present the case of a three-year-old boy who came with a large non-tender mass in the right upper abdomen for six months. Ultrasound abdomen revealed a huge heterogenous mass anterior to the right kidney and inferior to the liver with internal vascularity and calcifications, mimicking a neuroblastoma. Tru-cut needle biopsy showed foetal-type hepatoblastoma. After neoadjuvant chemotherapy, the tumour was explored. It was found to be adherent to the inferior surface of the liver with no capsular breech. Hence differentiating it from exophytic growth of hepatoblastoma. The tumour was completely resected. The postoperative course was uneventful and adjuvant chemotherapy was given. So far only a few cases of extrahepatic hepatoblastoma have been reported.

Effectiveness of indocyanine green fluorescence imaging in resection of hepatoblastoma.

OBJECTIVE: The present research aimed to analyze the application of indocyanine green (ICG) fluorescence contrast technique in the resection of hepatoblastoma (HB) in children, and to discuss the use of ICG in the surgery of HB and the value of guidance. METHODS: We retrospectively analyzed the data of 23 children with HB resected using ICG fluorescence contrast technique at the Children's Hospital of Nanjing Medical University from June 2020 to September 2022, including 16 boys and 7 girls, aged 5 days to 80 months. The patients were administered with an ICG injection of 0.1 mg/kg around 24-48 h before surgery. The surgical margin was detected by real-time fluorescence imaging and confirmed by postoperative pathology. RESULTS: All primary lesions showed bright fluorescence in 23 HB cases. 22 had clear borders with normal liver tissue, while one neonatal case showed no difference between tumor and background. 13 anatomic resection and 10 non-anatomic resection were performed with ICG fluorescence navigation. The surface of the residual liver was scattered with multiple tumor fluorescence, which was then locally enucleated according to the fluorescence. 22 isolated specimens were dissected and fluorescently visualized. Pathology identified deformed, vacuolated and densely arranged hepatocytes resembling pseudo-envelope changes without tumor residual, due to the compression of the tissue at the site of circumferential imaging. CONCLUSION: The ring ICG fluorescence imaging of HB indicates the tumor resection boundary effectively, especially in multiple lesions cases.

Lung and right atrial metastases from hepatoblastoma in children: A case series and literature review.

Hepatoblastoma (HB) in children with both lung and right atrial metastases is an unusual situation. The therapy for these cases is challenging and the prognosis is not good. We present three children with HB showing both lung and right atrial metastases and who underwent surgery and received preoperative/postoperative adjuvant-combined chemotherapy to achieve complete remission. Therefore, HB with lung and right atrial metastases could have a good prognosis through active and multidisciplinary treatment.

Aggressive Pursuit of No Evidence of Disease Status in Hepatoblastoma Improves Survival: An Observational Study.

BACKGROUND: The utility of repeated surgical interventions in hepatoblastoma to achieve no evidence of disease (NED) is not well-defined. We examined the effect of aggressive pursuit of NED status on event-free (EFS) and overall survival (OS) in hepatoblastoma with subgroup analysis of high-risk patients. METHODS: Hospital records were queried for patients with hepatoblastoma from 2005 to 2021. Primary outcomes were OS and EFS stratified by risk and NED status. Group comparisons were performed using univariate analysis and simple logistic regression. Survival differences were compared with log-rank tests. RESULTS: Fifty consecutive patients with hepatoblastoma were treated. Forty-one (82%) were rendered NED. NED was inversely correlated with 5-year mortality (OR 0.006; CI 0.001-0.056; P < .01). Ten-year OS (P < .01) and EFS (P < .01) were improved by achieving NED. Ten-year OS was similar between 24 high-risk and 26 not high-risk patients when NED was attained (P = .83). Fourteen high-risk patients underwent a median of 2.5 pulmonary metastasectomies, 7 for unilateral disease, and 7 for bilateral, with a median of 4.5 nodules resected. Five high-risk patients relapsed, and three were salvaged. CONCLUSIONS: NED status is necessary for survival in hepatoblastoma. Repeated pulmonary metastasectomy and/or complex local control strategies to obtain NED can achieve long-term survival in high-risk patients. LEVEL OF EVIDENCE: Level III - Treatment Study - Retrospective Comparative Study.

Indocyanine green navigation in minimally invasive resection of multiple metachronous pulmonary metastases of hepatoblastoma.

Pulmonary metastases from hepatoblastoma (HB) have traditionally been identified by preoperative computed tomography scan image evaluation, and intraoperative visual and palpatory examinations through thoracotomy have been generally recommended. However, the safety and accuracy of surgery can be problematic in patients with small multiple lung metastases due to postoperative respiratory dysfunction risk secondary to decreased residual lung capacity in wedge resections. We present an 8-month-old patient with metastatic HB with multiple metachronous pulmonary lesions in whom thoracoscopic lung resections were performed guided by indocyanine green (ICG) administered intravenously 24 h earlier (0.5 mg/kg). ICG fluorescence allowed identification and limited resection of lung parenchyma, avoiding postoperative respiratory dysfunction. A total of 16 lung lesions were resected during four operations (two bilateral and two right thoracoscopies), with no postoperative complications. ICG-guided thoracoscopic surgery allowed identification and resection of metastatic nodules in both lungs during the same procedure, achieving a hospital stay of less than 3 days for each intervention. The patient is currently 24 months old and remains asymptomatic, with no distant disease at the last imaging control. ICG-guided resection via a thoracoscopic approach is particularly useful in patients with multiple and/or metachronous metastases requiring multiple surgical interventions.

Surgical management in hepatoblastoma: points to take.

Hepatoblastoma is the most common primary malignant paediatric liver tumour and surgery remains the cornerstone of its management. The aim of this article is to present the principles of surgical treatment of hepatoblastoma. All aspects of surgery in hepatoblastoma are discussed, from biopsy, through conventional and laparoscopic liver resections, to extreme resection with adjacent structures, staged hepatectomy and transplantation.

Repeat hepatectomy for pediatric recurrent chemotherapy-resistant hepatoblastoma: a report of 18 cases.

BACKGROUND AND AIMS: Repeat hepatectomy for adult recurrent hepatocellular carcinoma significantly prolongs the overall survival, but repeat hepatectomy for pediatric recurrent hepatoblastoma (HB) is rarely reported, and the outcomes are warranted to be investigated. METHODS: All patients between May 2015 and December 2020 with recurrent HB after intended surgical cure were retrospectively evaluated. Clinicopathologic features, surgical details and outcomes were analyzed during a median following-up of 24 months after repeat hepatectomy. Survival analysis was performed using the Kaplan-Meier estimate. RESULTS: A total of 18 patients of recurrent HB undergoing repeat hepatectomy with radical cure intention were included. There were 11 males and 7 females. The median age was 29 months (range 5-87 months) at first hepatectomy, and the median time to the recurrence from the first hepatectomy was 7 months. The operating time of the repeat hepatectomy was 5.0 h (range 3.5-9.0 h) and the mean blood loss was 592 ml (range 50-3200 ml). Radical resection (R0) was achieved in 12 patients (66.7%), with a postoperative hospital stay of 7.9 ± 1.8 days. No serious postoperative complications or mortality occurred. The overall survival (OS) rate was 55.6% (10/18) and the event-free survival (EFS) rate was 33.3% (6/18). Those with no lung metastases, not high-risk stratification, and achieving R0 hepatectomy, anatomic hepatectomy had longer OS rate (all P < 0.05) after repeat hepatectomy. Two of three patients with re-recurrence HB undergoing salvage liver transplantation were alive with a tumor-free survival. CONCLUSIONS: Repeat hepatectomy for recurrent HB can be carried out safely. However, only a highly selected subgroup of patients might actually benefit from this procedure.