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.

Indocyanine green is a sensitive adjunct in the identification and surgical management of local and metastatic hepatoblastoma.

BACKGROUND: Hepatoblastoma is the most common primary pediatric liver malignancy. Indocyanine green (ICG) has been described as an adjunct to resection in small series. Its utility remains undefined in larger cohorts. METHODS: Records for 29 patients diagnosed with hepatoblastoma who received ICG prior to surgical resection from 2017 to 2020 at a single institution were retrospectively reviewed. The primary outcome was correlation between intraoperative ICG-avidity and histologic presence of hepatoblastoma. A secondary outcome included the histologic margin designation for resected liver specimens. RESULTS: ICG sensitivity was 91% for 120 resected thoracic specimens from 21 patients. Specificity was 57%. In 10% of operations, HB-positive specimens were resected solely on ICG-avidity. In an additional 40% of cases, ICG assisted in localizing a preoperatively diagnosed lesion. ICG sensitivity during thoracotomy and thoracoscopic surgery was 95 and 74%, respectively; primary and relapsed disease demonstrated sensitivity of 94 and 73%, respectively. Sensitivity was 92% for 25 resected liver specimens from nine patients with all parenchymal margins grossly negative for disease. Four multifocal lesions were identified with two resected solely by ICG-avidity. CONCLUSIONS: ICG is a sensitive adjunct for identifying local and metastatic hepatoblastoma, including lesions not visualized on preoperative imaging, and delineating margins during liver resection. False positives limit specificity; however, there were no adverse outcomes from additional resections. We noted that thoracoscopic surgery can be completed safely in patients with less significant disease burden, and conversion to thoracotomy, if necessary, is straightforward.

Liver Transplant for Posthepatectomy Liver Failure in Hepatoblastoma.

OBJECTIVES: Predicting the risk of posthepatectomy liver failure is important when performing extended hepatectomy. However, there is no established method to evaluate liver function and improve preoperative liver function in pediatric patients. MATERIALS AND METHODS: We show the clinical features of pediatric patients who underwent living donor liver transplant for posthepatectomy liver failure in hepatoblastoma. The subjects were 4 patients with hepatoblastoma who were classified as Pretreatment Extent of Disease III, 2 of whom had distal metastasis (chest wall and lung). RESULTS: Hepatic right trisegmentectomy was performed in 3 patients and extended left hepatectomy in 1 patient. The median alpha-fetoprotein level at the diagnosis of hepatoblastoma was 986300 ng/mL (range, 22500-2726350 ng/mL), and the median alpha-fetoprotein level before hepatectomy was 8489 ng/mL (range, 23-22500 ng/mL). The remnant liver volume after hepatectomy was 33.3% (range, 20% to 34.9%). Four patients had cholangitis after hepatectomy and progressed to posthepatectomy liver failure. The peak serum total bilirubin after hepatectomy was 11.4 mg/dL (range, 8.7-14.6 mg/dL). Living donor liver transplant was performed for these 4 patients with posthepatectomy liver failure, and they did not have a recurrence. CONCLUSIONS: When the predictive remnant liver volume by computed tomography-volumetry before extended hepatectomy for patients with hepatoblastoma is less than 40%, the possibility of posthepatectomy liver failure should be recognized.

Computed tomography imaging and clinical features of congenital hepatoblastoma: A retrospective analysis.

Congenital hepatoblastoma (CHB) is the most common hepatic malignant tumor of fetus or neonates, but few studies focusing on the radiological characteristics of CHB have been reported to date.To investigate the characteristic clinical and computed tomography (CT) findings of CHB to facilitate recognition and noninvasive diagnosis.Medical records of 7 patients with CHB were retrospectively reviewed. The demographic, clinical, and laboratory data were extracted from the electronic medical records. Two pediatric radiologists evaluated the abdominal CT examinations for the hepatic tumor location, size, enhancement characteristics, vascular invasion, and intra-/extra-hepatic metastasis.Among the included 7 patients (3 males and 4 females), only 1 had an elevated serum alpha-fetoprotein level. All patients had solitary intrahepatic mass with a mean size of 4.7 cm (range: 2.9-10.2 cm), of which liver SV-VII were most involved. 4/7 tumors were round while 3/7 irregular or lobulated. 6/7 tumors were well-defined. Microhemorrhage, cystic necrosis, and coarse calcification were present in 5/7, 4/7, and 1/7 tumors, respectively. All lesions showed inhomogeneously significant enhancement, with multiple nodular or striped appearance in the center and periphery of the tumors on the arterial phase, and then the enhancement area showed progressive expansion and fusion filling over time but the attenuation gradually declined on the portal and delayed phases, and finally the majority (6/7) of tumors presented multiple band- or island-like characteristics with prominently peripheral enhancement on the delayed phase while the remaining 1 relatively small tumor showed nearly complete but inhomogenous enhancement. In addition, only 1/7 tumor had hilar hepatic bile duct and portal vein invasion and secondary intra-hepatic bile duct dilation. No metastatic lesions were identified in all patients at diagnosis. The abdominal aorta distal to the coeliac trunk was significantly narrowed in 3/7 patients. Pathological examinations suggested that 6/7 tumors showed fetal histology with only 1 containing mesenchymal elements.The relationship between serum alpha-fetoprotein and CHB could be more complicated and yet to be determined. Dynamic contrast-enhanced CT can facilitate recognition and noninvasive diagnosis of CHB, presenting a pattern of progressive expansion and fusion filling but inhomogeneously significant enhancement.

Novel treatment of refractory / recurrent pulmonary hepatoblastoma.

BACKGROUND: There is no consensus about how to manage pulmonary metastasis in patients with hepatoblastoma. We reviewed a treatment with a combination of oxaliplatin, vincristine, and topotecan (OVT) paired with radiofrequency ablation (RFA) of 12 patients with multiple refractory / recurrent pulmonary hepatoblastoma. METHODS: The medical records from patients with ≤21 years of age presenting with multiple deposits (≥2) of refractory / recurrent pulmonary hepatoblastoma were reviewed. The following data were extracted from each patient: age, gender, histological subtyping, cycles of OVT, tumor size, biomarkers, chemotherapy regimen and dosage, RFA details, treatment response, follow up, and patient outcomes. The primary outcome measure was the complete response (CR) of pulmonary diseases, and secondary outcomes were event-free survival rate and overall survival rate. RESULTS: Of 12 assessable patients, three (25%) (95% CI, 46.3-104) patients achieved PR (partial resopnse) after they finished OVT. After RFA, five (41.7%) (95% CI, 8.95-74.4) patients achieved CR (complete response). The 2 year event-free survival rate was 33% (95% CI, 20.5-64.6). The 2 year overall survival for the study group was 41.7% (95% CI, 8.9-74.4). All toxicity events were handled satisfactorily and no toxic related deaths were observed. CONCLUSIONS: Our review report shows that OVT combined with RFA can be a successful treatment modality for previously heavily treated refractory / recurrent pulmonary metastatic lesions from hepatoblastoma.

Reiterative Radiofrequency Ablation in the Management of Pediatric Patients with Hepatoblastoma Metastases to the Lung, Liver, or Bone.

BACKGROUND AND PURPOSE: Conventional treatments of systemic chemotherapy and surgical resection for recurrent or metastatic hepatoblastoma (HB) may be inhibitive for the pediatric patient and family who have already been through extensive therapies. This single-institution case series evaluates the safety and efficacy of percutaneous radiofrequency ablation (RFA) in the management of metastatic HB. MATERIALS AND METHODS: Between March 2008 and February 2015, RFA was used as part of multidisciplinary management for HB recurrence or metastasis in 5 children (median 5.0 years old) in an attempt to provide locoregional control and preclude additional surgery. Combined local treatments of 38 metachronous metastases included surgical metastasectomy (14 lesions: 7 lung, 7 liver), percutaneous RFA (23 lesions: 21 lung, 1 liver, 1 bone), and stereotactic radiotherapy (1 liver lesion). RESULTS: For lesions treated with RFA (median diameter 6 mm, range 3-15 mm), local control was achieved in 22/23 metastases (95.6%) with median follow-up of 30.1 months after RFA (range 18.9-65.7). Median hospitalization was 3 days (2-7), with major complications limited to 1 pneumothorax requiring temporary small-caliber chest tube. Four children remain in complete remission with median follow-up of 67 months (range 41.2-88.8) after primary tumor resection, with mean disease-free survival of 31.7 months after last local treatment. One child succumbed to rapidly progressive disease 12 months after RFA (23.9 months after primary tumor resection). CONCLUSION: RFA provides a safe and effective reiterative treatment option in the multidisciplinary management of children with metastatic HB.

Metastasectomy of Hepatoblastoma Utilizing a Novel Overlay Fluorescence Imaging System.

BACKGROUND: The curability of hepatoblastoma (HB) largely depends on the achievement of radical surgical resection, even for metastatic tumors. However, the extension of the metastatic tumor when viewed through an endoscope with the conventional white-light mode is often unclear. Advancements in imaging technology utilizing indocyanine green (ICG) have facilitated precise resection of metastatic HBs, owing to the longer retention of ICG in such lesions than in other normal tissues. CASE: We utilized an endoscope loaded with the PINPOINT system (NOVADAQ Technologies, Inc., Ontario, Canada), which allows for real-time overlay visualization with the same focal range between the white-light mode and near-infrared mode. Metastatic HBs that have taken up ICG are visualized as an area of green color superimposed on a high-definition white-light image. A 19-year-old female who underwent liver transplantation for an unresectable HB 2 years earlier was noted to have metastases on the diaphragm and the pleura. Preoperative magnetic resonance imaging showed metastatic HBs on the right pleura extending from the ribs and the diaphragm. The margin of the metastatic tumor was more sharply demarcated by the PINPOINT system than that detected in the normal white-light mode. The tumor was successfully resected en bloc with real-time guidance utilizing the overlay image. The alphafetoprotein levels were normalized and have remained within normal limits in the 12 months since the operation. CONCLUSION: Novel overlay imaging technology with ICG makes it possible to achieve real-time precise resection of metastatic HBs.

Pediatric patient with end-stage kidney disease secondary to Eagle-Barrett syndrome and metastatic unresectable hepatoblastoma treated successfully with chemotherapy and liver-kidney transplant.

HBL is the most common malignant liver neoplasm in children. The etiology of HBL is largely unknown but there are certain syndromes, such as Beckwith-Wiedemann syndrome, that have been clearly associated with an increased incidence of this malignancy. EBS, also known as prune belly syndrome, is a congenital anomaly characterized by lax abdominal musculature, bilateral cryptorchidism requiring, in some cases, hemodialysis due to significant kidney and urinary tract dysfunctions. Despite an improvement on the survival rates of patients with advanced-stage HBL, the presence of concomitant end-stage renal disease that occurs in patients with EBS constitutes a therapeutic challenge for the clinician not only due to the use of nephrotoxic chemotherapy but also due to the potential need for multi-organ transplant. We report case of a 2-year-old male patient with EBS diagnosed with stage IV, metastatic HBL successfully treated with multi-agent chemotherapy while on dialysis whom then underwent a simultaneous liver-kidney transplant followed by adjuvant chemotherapy. Ultimately, the patient achieved cancer remission with normalization of his renal function. Our report emphasizes that patients with HBL in the setting of EBS will not only require careful kidney function monitoring while receiving chemotherapy, but they might also need to undergo multi-organ transplantation in order to achieve adequate cancer control and also normalization of their kidney function. Awareness of this unusual association calls for further investigation to potentially establish a genetic association between these two disease processes.

General paucity of genomic alteration and low tumor mutation burden in refractory and metastatic hepatoblastoma: comprehensive genomic profiling study.

Hepatoblastoma (HBL) is a hepatic malignancy of infants and young children, which is often cured by combinations of surgery and chemotherapy. Management of refractory and metastatic HBL is challenging. Comprehensive genomic profiling was performed on 31 refractory and metastatic HBL using a hybrid-capture, adaptor ligation-based next-generation sequencing assay. Tumor mutation burden (TMB) was calculated from a minimum of 1.11 Mb of sequenced DNA and reported as mutations/Mb. The results were analyzed for all classes of genomic alterations (GA). Activating CTNNB1 mutation was the most frequent GA seen in 19 (61%) of cases. All 3 (100%) mixed epithelial and mesenchymal HBL harbored CTNNB1 mutation. The small cell undifferentiated subtype showed SMARCB1 loss in both cases. There was no significant further correlation of GA with histologic subtype. In addition to the potential targeting of CTNNB1, other rarely identified possible targetable GA included ERBB4 (6%) and FBXW7, SRC and BRCA2 (each at 3%). The mean TMB was 3.5 mut/Mb, the median was 1.7 mut/Mb. There were 2 HBL with ≥10 mut/Mb. No alterations in TP53 were identified, and alterations in the DNA repair pathways were rare. Refractory and metastatic HBL is characterized by a general paucity of GA and is dominated by frequent CTNNB1 mutation and overall low TMB. Although potentially targetable GA are seen on occasion in HBL and a small number of cases have high TMB with potential to respond to immune checkpoint inhibitors, advanced HBL will remain a treatment challenge.

Clinical application of projection mapping technology for surgical resection of lung metastasis.

Indocyanine green fluorescent image-guided surgery was developed to identify primary and metastatic nodules of various malignancies. However, currently, surgeons need to identify the fluorescent image on a monitor, which impedes surgical procedures. Herein, we developed a novel projection mapping device that can cast the real-time fluorescent image onto the surface of the targeted organ. We performed surgical resection of a lung metastasis of hepatoblastoma using this technique. The projection mapping technique clearly detected the pulmonary lesion, and no other lesions were identified in the ipsilateral thorax. The patient is well and free of recurrence 2 years after surgery.

The role of pulmonary metastasectomy for hepatoblastoma in children with metastasis at diagnosis: Results from the JPLT-2 study.

BACKGROUND/PURPOSE: The purpose of this study was to clarify the role of pulmonary metastasectomy in hepatoblastomas with lung metastasis at diagnosis. We reviewed cases enrolled in the JPLT-2 study. METHODS: A total of 360 cases with hepatoblastoma were enrolled. The clinical courses and outcome of 60 cases with pulmonary metastasis at diagnosis were reviewed, focusing on metastasectomy. RESULTS: Induction chemotherapy resulted in eradication of nodules in 26, residual nodules in 33, and early treatment-related death in one. Of the 33 cases with residual nodules, 11 underwent complete resection of the lung lesions, and among these, progression was reported in five. Complete resection of the liver tumor was not achieved in two of these. Three underwent incomplete resection of lung nodules, eventually leading to progression. Twelve cases with incomplete or no liver tumor resection progressed regardless of the status of lung lesions. Contrarily, among patients who underwent complete resection of the liver tumor, half were cured without metastasectomy. CONCLUSIONS: Metastasectomy for residual pulmonary nodules after induction chemotherapy is effective provided that the liver tumor could be completely resected. TYPE OF STUDY: Prospective Cohort Study. LEVEL OF EVIDENCE: Level II.

A systematic surgical approach to hepatoblastoma with intracardiac extension.

Hepatoblastoma is very uncommon in children, and intracardiac extension is rare. The SIOPEL-4 regime for metastatic hepatoblastoma has extended the surgical options with good results. We successfully treated a boy aged 2 years and 9 months with hepatoblastoma, using a multidisciplinary surgical strategy involving an extended left hepatectomy, left adrenalectomy, biopsy of the paraaortic and coeliac lymph nodes, and resection of the inferior vena caval-right atrial extension of the hepatoblastoma, under cardiopulmonary bypass and deep hypothermia.

Upfront window vincristine/irinotecan treatment of high-risk hepatoblastoma: A report from the Children's Oncology Group AHEP0731 study committee.

BACKGROUND: The identification of new therapies for high-risk (HR) hepatoblastoma is challenging. Children's Oncology Group study AHEP0731 included a HR stratum to explore the efficacy of novel agents. Herein, the authors report the response rate to the combination of vincristine (V) and irinotecan (I) and the outcome of patients with high-risk hepatoblastoma. METHODS: Patients with newly diagnosed metastatic hepatoblastoma or those with a serum α-fetoprotein (AFP) level <100 ng/mL were eligible. Patients received 2 cycles of V at a dose of 1.5 mg/m2 /day intravenously on days 1 and 8 and I at a dose of 50 mg/m2 /day intravenously on days 1 to 5. Patients were defined as responders if they had either a 30% decrease in tumor burden according to Response Evaluation Criteria In Solid Tumors (RECIST) or a 90% (>1 log10 ) decline in their AFP level. Responders were to receive 2 additional cycles of VI intermixed with 6 cycles of the combination of cisplatin, doxorubicin, 5-fluorouracil, and vincristine (C5VD). Nonresponders were to receive 6 cycles of C5VD alone. RESULTS: A total of 32 patients with a median age at diagnosis of 26 months (range, 11-159 months) were enrolled between September 2009 and February 2012. Fourteen of 30 evaluable patients were responders (RECIST and AFP in 6 patients, RECIST only in 3 patients, and AFP only in 5 patients). The median AFP decline after 2 cycles of VI for the entire group was 345,565 ng/mL (85% of the initial AFP). The 3-year event-free and overall survival rates were 49% (95% confidence interval, 30%-65%) and 62% (95% confidence interval, 42%-77%), respectively. CONCLUSIONS: The VI combination appears to have substantial activity against HR hepatoblastoma. The ultimate impact of this regimen in improving the outcomes of children with HR hepatoblastoma remains to be determined. Cancer 2017;123:2360-2367. © 2017 American Cancer Society.

Risk-stratified staging in paediatric hepatoblastoma: a unified analysis from the Children's Hepatic tumors International Collaboration.

BACKGROUND: Comparative assessment of treatment results in paediatric hepatoblastoma trials has been hampered by small patient numbers and the use of multiple disparate staging systems by the four major trial groups. To address this challenge, we formed a global coalition, the Children's Hepatic tumors International Collaboration (CHIC), with the aim of creating a common approach to staging and risk stratification in this rare cancer. METHODS: The CHIC steering committee-consisting of leadership from the four major cooperative trial groups (the International Childhood Liver Tumours Strategy Group, Children's Oncology Group, the German Society for Paediatric Oncology and Haematology, and the Japanese Study Group for Paediatric Liver Tumours)-created a shared international database that includes comprehensive data from 1605 children treated in eight multicentre hepatoblastoma trials over 25 years. Diagnostic factors found to be most prognostic on initial analysis were PRETreatment EXTent of disease (PRETEXT) group; age younger than 3 years, 3-7 years, and 8 years or older; α fetoprotein (AFP) concentration of 100 ng/mL or lower and 101-1000 ng/mL; and the PRETEXT annotation factors metastatic disease (M), macrovascular involvement of all hepatic veins (V) or portal bifurcation (P), contiguous extrahepatic tumour (E), multifocal tumour (F), and spontaneous rupture (R). We defined five clinically relevant backbone groups on the basis of established prognostic factors: PRETEXT I/II, PRETEXT III, PRETEXT IV, metastatic disease, and AFP concentration of 100 ng/mL or lower at diagnosis. We then carried the additional factors into a hierarchical backwards elimination multivariable analysis and used the results to create a new international staging system. RESULTS: Within each backbone group, we identified constellations of factors that were most predictive of outcome in that group. The robustness of candidate models was then interrogated using the bootstrapping procedure. Using the clinically established PRETEXT groups I, II, III, and IV as our stems, we created risk stratification trees based on 5 year event-free survival and clinical applicability. We defined and adopted four risk groups: very low, low, intermediate, and high. INTERPRETATION: We have created a unified global approach to risk stratification in children with hepatoblastoma on the basis of rigorous statistical interrogation of what is, to the best of our knowledge, the largest dataset ever assembled for this rare paediatric tumour. This achievement provides the structural framework for further collaboration and prospective international cooperative study, such as the Paediatric Hepatic International Tumour Trial (PHITT). FUNDING: European Network for Cancer Research in Children and Adolescents, funded through the Framework Program 7 of the European Commission (grant number 261474); Children's Oncology Group CureSearch grant contributed by the Hepatoblastoma Foundation; Practical Research for Innovative Cancer Control and Project Promoting Clinical Trials for Development of New Drugs and Medical Devices, Japan Agency for Medical Research; and Swiss Cancer Research grant.

Loss of EGFR-ASAP1 signaling in metastatic and unresectable hepatoblastoma.

Hepatoblastoma (HBL), the most common childhood liver cancer is cured with surgical resection after chemotherapy or with liver transplantation if local invasion and multifocality preclude resection. However, variable survival rates of 60-80% and debilitating chemotherapy sequelae argue for more informed treatment selection, which is not possible by grading the Wnt-ß-catenin over activity present in most HBL tumors. A hypothesis-generating whole transcriptome analysis shows that HBL tumors removed at transplantation are enriched most for cancer signaling pathways which depend predominantly on epidermal growth factor (EGF) signaling, and to a lesser extent, on aberrant Wnt-ß-catenin signaling. We therefore evaluated whether EGFR, ASAP1, ERBB2 and ERBB4, which signal downstream after ligation of EGF, and which show aberrant expression in several other invasive cancers, would also predict HBL tumor invasiveness. Immunohistochemistry of HBL tumors (n = 60), which are histologically heterogeneous, shows that compared with well-differentiated fetal cells, less differentiated embryonal and undifferentiated small cells (SCU) progressively lose EGFR and ASAP1 expression. This trend is exaggerated in unresectable, locally invasive or metastatic tumors, in which embryonal tumor cells are EGFR-negative, while SCU cells are EGFR-negative and ASAP1-negative. Loss of EGFR-ASAP1 signaling characterizes undifferentiated and invasive HBL. EGFR-expressing HBL tumors present novel therapeutic targeting opportunities.

Surgical treatment of pulmonary metastases in pediatric solid tumors.

Most children who succumb to solid malignancies do so because of the burden of metastatic disease or due to complications associated with the therapy administered to treat metastatic disease. Approximately one-quarter of children with solid tumors will present with metastatic disease, and an additional 20% ultimately develop metastatic disease, most commonly in the lung. The role of surgery in the treatment of metastatic solid tumors, given its disseminated nature, is not intuitive, yet there are circumstances in which surgical resection of metastatic disease can potentially be curative. However, the utility of surgery is very much dependent on histology, and generally is most appropriate for those malignancies with histologies that are refractory to other adjuvant therapies.

Multidisciplinary effort in treating children with hepatoblastoma in China.

The purpose of this study is to report the first nationwide protocol (Wuhan Protocol) developed by Chinese Children's Cancer Group and the results of multidisciplinary effort in treating hepatoblastoma. In this study, we reported the final analysis, which includes 153 hepatoblastoma patients in 13 hospitals from January 2006 to December 2013. The 6-year overall survival and event-free survival rates were 83.3 ± 3.1% and 71.0 ± 3.7%, respectively, in this cohort. The univariate analysis revealed that female (P = 0.027), under 5 years of age (P = 0.039), complete surgical resection (P = 0.000), no metastases (P = 0.000), and delayed surgery following neoadjuvant chemotherapy (P = 0.000) had better prognosis. In multivariate analysis, male, 5 years of age or above, stage PRETEXT III or IV, and incomplete surgical resection were among the some adverse factors contributing to poor prognosis. The preliminary results from this study showed that patients who underwent treatment following Wuhan Protocol had similar OS and EFS rates compared to those in developed countries. However, the protocol remains to be further optimized in standardizing surgical resection (including liver transplantation), refining risk stratification and risk-based chemotherapy.

Relapsed hepatoblastoma confined to the lung is effectively treated with pulmonary metastasectomy.

BACKGROUND: In children diagnosed with hepatoblastoma (HB), the lungs are the most common site of metastasis at both initial presentation and relapse. Previous studies have encouraged pulmonary metastasectomy to achieve a disease-free state after resection of the primary hepatic lesion. However, there is no consensus about how to manage recurrent pulmonary metastasis. PROCEDURE: A retrospective, multi-institutional review was performed from 2005 to 2014 to identify HB patients ≤18years of age who had disease recurrence associated with pulmonary metastases alone. RESULTS: Ten patients between the ages of 8 and 33months were identified. Pulmonary metastatic recurrence was detected by measuring alpha-fetoprotein (AFP) levels and/or with CT scans of the chest. All patients subsequently underwent pulmonary metastasectomy without post-operative complications. At last follow-up, 8 patients were alive and had normal AFP levels. The 8 survivors had a median follow-up from therapy completion of 18.5months. Two patients who presented with extrapulmonary recurrence subsequently died of treatment refractory disease. CONCLUSIONS: This review supports surgical resection as a safe and, in the context of multimodal therapy, efficacious approach to manage HB patients who present with isolated pulmonary relapse.

Heart Failure and Main Pulmonary Artery Obstruction Caused by Right Ventricular Metastatic Adult Hepatoblastoma: A Case Report.

We report a case of a 18-year-old boy who presented with dyspnea and right upper quadrant abdominal dull pain. According to urgent echocardiography, a dense sessile mass occupied the right ventricule. Tumor resection was performed, followed by further adjuvant therapy. The specimen was histopathologically investigated and eventually diagnosed as metastatic adult hepatoblastoma. We discuss its clinical features and treatment in the light of the current knowledge. It is important for us to be aware that adjuvant chemotherapy might be an effective alternative in the treatment of hepatoblastoma combined with ventricle invasion. Early cardiac surgery may be advised in patients with cardiac function impairment.

Expression of RECK and MMPs in Hepatoblastoma and Neuroblastoma and Comparative Analysis on the Tumor Metastasis.

OBJECTIVE: To explore the expression of RECK and relevant matrix metalloproteinases (MMPs) in hepatoblastoma (HB) and neuroblastoma (NB) and their clinical significance in the tumor metastasis. MATERIALS AND METHODS: Forty-five wax-stone samples of HB and 43 wax-stone samples of NB removed by surgical resection and confirmed by pathology in Linyi Yishui Central Hospital were selected. According to presence and absence of metastasis, both NB and HB samples were divided into metastatic group and non-metastatic group, namely NB metastatic group (n=28), NB non-metastatic group (n=15), HB metastatic group (n=15) and HB non-metastatic group (n=30). The expression of RECK, membrane type-1 matrix metalloproteinase (MT1-MMP) in HB tissue and RECK, MMP-14 in NB tissue was detected using immunohistochemical method, and the correlation between RECK and MT1-MMP, MMP-14 was analyzed. RESULTS: The metastatic rate of NB was dramatically higher than that of HB, with statistical significance (P=0.003). The positive rate of RECK expression in NB group (30.2%) was slightly lower than in HB group (40.0%), but no significant difference was presented (P=0.338). The positive rate of MMPs expression in NB metastatic group was evidently higher than in HB metastatic group (P=0.024). The results of Spearman correlation analysis revealed that the expression of RECK in HB and NB tissues had a significantly-negative correlation with MT1-MMP and MMP-14, respectively (r=-0.499, P=0.012; r=-0.636, P=0.000). CONCLUSIONS: In HB and NB tissues, RECK is expressed lowly, while relevant MMPs highly, and RECK inhibits the tumor invasion and metastasis through negative regulation of relevant MMPs.