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Hiyama E, Hishiki T, Watanabe K, et al.
Resectability and tumor response after preoperative chemotherapy in hepatoblastoma treated by the Japanese Study Group for Pediatric Liver Tumor (JPLT)-2 protocol.
J Pediatr Surg. 2016; 51(12):2053-2057 [PubMed] Related Publications

BACKGROUND/PURPOSE: We aimed to clarify whether surgical resectability and tumor response after preoperative chemotherapy (preCTx) represented prognostic factors for patients with hepatoblastoma (HBL) in the JPLT-2 study (1999-2012).
METHODS: Patients (N=342) with HBL who underwent preCTx were eligible. PRETEXT, CHIC risk stratification (standard [SR], intermediate [IR] and high risk [HR]) at diagnosis, POST-TEXT, and tumor resectability were evaluated by imaging. Tumor response was classified into responders (CR or PR) and nonresponders (NC or PD) according to RECIST criteria.
RESULTS: There were 7 PRETEXT I, 106 II, 143 III, and 86 IV, including 71 metastatic HBLs. In POST-TEXT, 12 PRETEXT II, 42 III, and 58 IV were down-staged. The 5-year EFS/OS rates of 198 SR, 73 IR, and 71 HR-HBLs were 82/94%, 49/64%, and 28/34%, respectively. In 198 SR, 154 of 160 responders and 24 of 38 nonresponders survived event-free (P<0.01). In 73 IR, 12 of 24 whose tumors remained unresectable experienced recurrence, 9 of whom were nonresponders (P<0.01). In 71 HR, chemoresponders and tumor resectability after preCTx correlated with favorable outcomes (P<0.05).
CONCLUSIONS: Evaluation of response and tumor resectability after preCTx is useful for predicting prognosis in HBLs. To improve outcomes, we should reconsider surgical procedures according to resectability and chemoresponsiveness.
LEVEL OF EVIDENCE: Level II.

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Ellerkamp V, Bortel N, Schmid E, et al.
Photodynamic Therapy Potentiates the Effects of Curcumin on Pediatric Epithelial Liver Tumor Cells.
Anticancer Res. 2016; 36(7):3363-72 [PubMed] Related Publications

BACKGROUND/AIM: Curcumin (CUM) is a promising agent in complementary oncology. The present study analyzed the photoactive properties of curcumin on pediatric epithelial liver tumor cell lines.
MATERIALS AND METHODS: Hepatoblastoma cell lines (HuH6, HepT1) and hepatocellular carcinoma cell lines (HepG2, HC-AFW1) were treated with curcumin and exposed to blue light (phototherapy, 480 nm, 300 W). Cell viability (MTT tests), cellular oxidative stress (production of reactive oxygen species (ROS)) and cellular uptake/degradation of curcumin were analyzed.
RESULTS: Significant loss of viability resulted from 24-48 h incubation with curcumin. With photodynamic therapy (PDT), even short time incubation (1 h) with curcumin resulted in significantly lower half maximal inhibitory concentration (IC50) (p<0.001, two-way ANOVA). Significant ROS production was observed with PDT and curcumin.
CONCLUSION: Phototherapy strongly enhances the anticancer properties of curcumin in pediatric solid liver tumors in vitro.

Related: Liver Cancer Childhood Liver Cancer

Terashima T, Yamashita T, Arai K, et al.
Response to chemotherapy improves hepatic reserve for patients with hepatocellular carcinoma and Child-Pugh B cirrhosis.
Cancer Sci. 2016; 107(9):1263-9 [PubMed] Free Access to Full Article Related Publications

There is no established treatment for patients with advanced hepatocellular carcinoma (HCC) with Child-Pugh class B cirrhosis. The aim of the present study was to assess the efficacy of hepatic arterial infusion chemotherapy (HAIC) according to Child-Pugh score (CPS) and to evaluate the correlation of a patient's response to HAIC with hepatic reserve and outcome. We retrospectively reviewed the medical records of 377 patients treated with HAIC between March 2003 and February 2015. Subjects included 179 with Child-Pugh class B. Median overall survival was 12.1 months for patients with CPS = 7 (n = 75) and 11.9 months for patients with CPS = 8 (n = 58), which were significantly longer compared with those of patients with CPS = 9 (n = 46, 6.3 months). The objective response rates of patients with CPS = 7, 8 and 9 were 26.7%, 27.6% and 6.5%, respectively. The CPS of responders improved significantly after HAIC, whereas those of nonresponders did not. A multivariate analysis demonstrated that improved CPS, responses to HAIC and absence of extrahepatic lesions were independent favorable prognostic factors. Patients with CPS = 7 or 8 tolerated HAIC, but nine (19.6%) of patients with CPS = 9 were unable to complete one course. HAIC is effective and safe for patients with a CPS = 7 or 8 and improved hepatic reserve of responders significantly.

Related: Liver Cancer

Okazaki E, Yamamoto A, Nishida N, et al.
Three-dimensional conformal radiotherapy for locally advanced hepatocellular carcinoma with portal vein tumour thrombosis: evaluating effectiveness of the model for end-stage liver disease (MELD) score compared with the Child-Pugh classification.
Br J Radiol. 2016; 89(1063):20150945 [PubMed] Article available free on PMC after 01/07/2017 Related Publications

OBJECTIVE: The purpose of this study was to retrospectively evaluate the effectiveness of the model for end-stage liver disease (MELD) score compared with the Child-Pugh classification in patients who received three-dimensional conformal radiotherapy (3D CRT) for hepatocellular carcinoma (HCC) with portal vein tumour thrombosis (PVTT) by analyzing toxicity and prognostic factors.
METHODS: 56 consecutive patients who had locally advanced HCC with PVTT treated by 3D CRT between September 2007 and April 2013 were retrospectively reviewed.
RESULTS: The median survival time of all patients was 6.4 months. Receiver-operating characteristic (ROC) analysis identified MELD score = 7.5 [area under the curve (AUC) 0.81] and Child-Pugh score = 6.5 (AUC 0.86) as the best cut-off values for predicting the incidence of complications over Common Terminology Criteria for Adverse Events grade 2. There was no significant difference in the discrimination power between the MELD score and the Child-Pugh score on comparison of the two ROC curves (p = 0.17). On multivariate analysis, age, MELD score and radiotherapy dose were significant prognostic factors for overall survival (p = 0.021, 0.038 and 0.006, respectively). In contrast, the Child-Pugh classification, tumour response, PVTT response and the number of prior interventional radiologic treatments were not significant on multivariate analysis.
CONCLUSION: This study showed that the best MELD score cut-off value is 7.5 and that the MELD score is a better prognostic factor than the Child-Pugh classification in 3D CRT for HCC with PVTT.
ADVANCES IN KNOWLEDGE: The MELD score is useful for predicting the risk of severe toxicities and the prognosis of patients treated with 3D CRT for PVTT.

Related: Liver Cancer

Zhang EL, Yang F, Wu ZB, et al.
Therapeutic efficacy of percutaneous microwave coagulation versus liver resection for single hepatocellular carcinoma ≤3 cm with Child-Pugh A cirrhosis.
Eur J Surg Oncol. 2016; 42(5):690-7 [PubMed] Related Publications

AIMS: This study aimed to compare the therapeutic efficacy of liver resection (LR) and percutaneous microwave coagulation therapy (PMCT) for single hepatocellular carcinoma ≤3 cm (HCC) in cirrhotic livers.
METHODS: In this study, 190 patients with single HCC ≤3 cm and Child-Pugh A cirrhosis were retrospectively reviewed. Among these patients, 122 patients underwent LR, and 68 patients received PMCT. The therapeutic efficacy and complications were compared between the two procedures.
RESULTS: There was no treatment-related hospital mortality in either group. Major complications were significantly more frequent in the LR group compared to the PMCT group (22.1% vs 5.9%, p = 0.004). The 1-, 3-, and 5-year OS rates for the LR group and PMCT group were 98.4%, 93.6%, 55.2% and 97.1%, 87.7%, 51%, respectively. There was no significant difference in OS rates between the LR group and PMCT group (p = 0.153). The 1-, 3-, and 5-year DFS rates were 96.7%, 70.5% and 43.7%, respectively, in the LR group, which were significantly higher compared to the PMCT group (92.6%, 50.5% and 26.3%, p = 0.006). Subgroup analyses revealed that HCC patients with portal hypertension (PH), OS and DFS were similar between the two groups.
CONCLUSIONS: LR may provide better DFS and lower recurrence rates than PMCT for single HCC ≤3 cm and Child-Pugh A cirrhosis. For HCC patients with PH, PMCT may provide therapeutic effects that are similar to LR.

Related: Liver Cancer

Yuan XJ, Wang HM, Jiang H, et al.
Multidisciplinary effort in treating children with hepatoblastoma in China.
Cancer Lett. 2016; 375(1):39-46 [PubMed] Related Publications

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.

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Tan L, Meier T, Kuhlmann M, et al.
Distinct set of chromosomal aberrations in childhood hepatocellular carcinoma is correlated to hepatitis B virus infection.
Cancer Genet. 2016; 209(3):87-96 [PubMed] Related Publications

Hepatocellular carcinoma (HCC) is rarely observed in children and adolescents, but it is reported to be correlated with hepatitis B virus (HBV+) infections. This correlation is not easily explained, because in adults, HBV infections lead to the development of HCC only after decades, not within a few years. In HBV+ adulthood HCC, distinct chromosomal imbalances have been observed. Similar analyses have not been reported for childhood HCC. Here, we investigated whether chromosomal changes were associated with childhood HCC. We analysed formalin-fixed paraffin-embedded (FFPE) samples derived from 17 patients, 0-18 years old, who underwent partial hepatectomies due to HBV+ or HBV- associated HCC. In parallel, in 15 cases, we also analysed non-neoplastic liver tissues adjacent to the HCC. All samples were analysed with high resolution, microarray-based, comparative genomic hybridisation (aCGH). Overall, genomic aberrations in childhood HCC resembled those reported for adulthood HCC. In HBV+ HCC samples, chromosomes 1, 6, 7, 9, 17, 19, and 22 were significantly changed compared to those in HBV- HCC samples. Most interestingly, aberrations for chromosomes 7, 8, 9, 11, and 19 were also observed in corresponding non-neoplastic samples. A specific set of chromosomal abnormalities, including gains in chromosomes 8q, 9q, 11q, and 19, was significantly enriched in HBV+ compared to HBV- non-neoplastic tissues. In childhood HCC, HBV+ was correlated to increased chromosomal instability and specific chromosomal imbalances. A subset of aberrations might be essential in HCC carcinogenesis because they occurred in adjacent, non-neoplastic tissues. In particular, the gain in chromosome 19 appeared to be highly important.

Related: CGH Liver Cancer Childhood Liver Cancer

Murawski M, Weeda VB, Maibach R, et al.
Hepatocellular Carcinoma in Children: Does Modified Platinum- and Doxorubicin-Based Chemotherapy Increase Tumor Resectability and Change Outcome? Lessons Learned From the SIOPEL 2 and 3 Studies.
J Clin Oncol. 2016; 34(10):1050-6 [PubMed] Related Publications

INTRODUCTION: The aim of this article is to present an experience of two prospective studies from the International Childhood Liver Tumor Strategy Group (SIOPEL 2 [S2] and SIOPEL [S3]) trials and to evaluate whether modified platinum- and doxorubicin-based chemotherapy is capable of increasing tumor resectability and changing patient outcomes.
METHODS: Between 1995 and 2006, 20 patients with hepatocellular carcinoma (HCC) were included in the S2 trial and 70 were included in the S3 trial. Eighty-five patients remained evaluable.
RESULTS: Response to preoperative chemotherapy was observed in 29 of 72 patients (40%) who did not have primary surgery, whereas 13 patients underwent upfront surgery. Thirty-three patients had a delayed resection. Thirty-nine tumors never became resectable. Complete tumor resection was achieved in 34 patients (40%), including seven of those treated with liver transplantation (LTX). After a median follow-up period of 75 months, 63 patients (74%) had an event (a progression during treatment, a relapse after treatment, or death from any cause). Sixty patients died. Twenty-three of 46 patients (50%) who underwent tumor resection died. Eighteen of 27 patients (63%) with complete tumor resection (without LTX) and 20 of 34 patients (59%) with LTX survived. Only one of seven patients (14%) with microscopically involved margins survived. Overall survival at 5 years was 22%.
CONCLUSION: Survival in pediatric HCC is more likely when complete tumor resection can be achieved. Intensification of platinum agents in the S2 and S3 trials has not resulted in improved survival. New treatment approaches in pediatric HCC should be postulated.

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Su L, Dong Q, Zhang H, et al.
Clinical application of a three-dimensional imaging technique in infants and young children with complex liver tumors.
Pediatr Surg Int. 2016; 32(4):387-95 [PubMed] Related Publications

INTRODUCTION: Three-dimensional (3D) imaging instead of two-dimensional (2D) computed tomography (CT) for diagnosis and preoperative planning in infants and young children with complex liver tumors is a promising technique for precision hepatectomy.
METHODS: This study was a retrospective analysis of 26 infants and young children with giant liver tumors involving the hepatic hilum who underwent precise hepatectomy at the Affiliated Hospital of Qingdao University between February 2012 and January 2015. All patients received upper abdominal contrast-enhanced CT scanning before surgery. 16 patients used Hisense CAS system for 3D reconstruction as the reconstruction group. While ten patients underwent 3D CT reconstruction by the CT Workstation as the control group. The clinical outcomes were analyzed and compared between the two groups. The 3D reconstruction of abdominal organs and blood vessels was generated using the Hisense CAS system. Diagnosis and preoperative planning assisted by the system was used for preoperative and intraoperative decision-making for precise hepatectomy.
RESULTS: All patients underwent successful surgery. The 3D models clearly demonstrated the association of liver tumors with the intrahepatic vascular system and provided a preoperative assessment of resectability, assisting surgeons in preoperative procedural planning. Anatomic hepatectomy was successfully completed in the reconstruction group. The mean operation time was shorter in the reconstruction group (137.81 ± 17.51 min) than in the control group (192 ± 34.66 min) (P < 0.01). The mean intraoperative blood loss was lesser in the reconstruction group (21.81 ± 14.05 ml) than in the control group (53.50 ± 21.35 ml) (P < 0.01). The difference was statistically significant.
DISCUSSION: 2D CT scan images cannot accurately display the spatial relationship between the tumor and surrounding vasculature. The 3D reconstruction model used in this study gave detailed and accurate anatomical information and allowed for the assessment of tumor resectability and provided a detailed road map for preoperative decision-making and predicted the postoperative liver function.
CONCLUSIONS: 3D visualization technology provides preoperative assessment and allows individualized surgical planning. Surgical controllability, accuracy, and safety can be improved in infants and young children undergoing precise hepatectomy for complex liver tumors.

Related: Liver Cancer

Ahmad N, Wheeler K, Stewart H, Campbell C
Hepatoblastoma in a mosaic trisomy 18 child with hemihypertrophy.
BMJ Case Rep. 2016; 2016 [PubMed] Related Publications

To date, there are 12 reported cases of hepatoblastoma in trisomy 18 patients, three of whom had a mosaic chromosome pattern. We report on an 18-month-old child who had hemihypertrophy and developmental delay, was found to have hepatoblastoma on surveillance ultrasound scan, and was subsequently diagnosed with mosaic trisomy 18 on array comparative genomic hybridisation from a peripheral blood sample and molecular cytogenetic analysis of the tumour specimen. Although hemihypertrophy has been associated with mosaic trisomies, there are only a couple of published case reports of hemihypertrophy or asymmetry in mosaic trisomy 18 patients and none in the reported cases of hepatoblastoma in a mosaic trisomy 18 setting. We have reviewed the published case reports of hepatoblastoma in trisomy 18 patients and found that they seem to tolerate the intensive treatment very well if there are no significant comorbidities.

Related: Chromosome 18 Hepatoblastoma Liver Cancer

Rosencrantz RA, LeCompte L, Yusuf Y
Beneath the Copper-Pediatric Wilson's Disease Cirrhosis and Hepatocellular Carcinoma: A Case Report with Literature Review.
Semin Liver Dis. 2015; 35(4):434-8 [PubMed] Related Publications

Primary hepatic malignancies are uncommon in pediatrics. Tumors such as hepatocellular carcinoma (HCC) develop typically in the setting of chronic liver disease. The incidence of HCC in Wilson's disease-related cirrhosis is disproportionately lower than in many other forms of end-stage liver disease. A preadolescent girl presented with Wilson's disease cirrhosis and a HCC requiring orthotopic liver transplantation. This case highlights the need to consider hepatic malignancies even in young Wilson's disease patients. Pediatric Wilson's disease and the hepatic tumor literature are reviewed.

Related: Liver Cancer Childhood Liver Cancer

Amesty MV, Chocarro G, Vilanova Sánchez A, et al.
Mesohepatectomy for Centrally Located Tumors in Children.
Eur J Pediatr Surg. 2016; 26(1):128-32 [PubMed] Related Publications

INTRODUCTION: Central hepatectomy or mesohepatectomy (MH) is a complex surgical technique rarely used in children. It is indicated in central tumors to preserve functioning liver mass avoiding an extended right hepatectomy. The purpose of this article is to analyze our experience with this technique.
METHODS: We reviewed five patients who underwent MH in the period from 2008 to 2014. Diagnoses were hepatoblastoma PRETEXT III (two cases), hepatic embryonal sarcoma (one case), focal nodular hyperplasia (one case), and vascular tumor with rapid growth in a newborn causing an acute liver failure, compartment syndrome, and multiple organ failure (one case). In all cases, the tumor was centrally located, including the segment IVb, with large displacement of the hepatic pedicle in two cases.
RESULTS: MH was standard in three cases and under total vascular exclusion in two cases. All children are alive with a mean follow-up of 38 (6-70) months. None of the children required reoperation because of bleeding. One child developed a biliary fistula in the cutting area that closed spontaneously. The newborn with the vascular tumor required the placement of a Gore-Tex patch (W. L. Gore & Associates, Inc, Flagstaff, Arizona, United States) to relieve the compartment syndrome. He subsequently underwent partial embolization of the tumor and MH under vascular exclusion.
CONCLUSIONS: In selected patients, MH is an alternative to trisegmentectomy and should be available in advanced pediatric hepatobiliary units.

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Liu B, Zhou L, Huang G, et al.
First Experience of Ultrasound-guided Percutaneous Ablation for Recurrent Hepatoblastoma after Liver Resection in Children.
Sci Rep. 2015; 5:16805 [PubMed] Article available free on PMC after 01/07/2017 Related Publications

This study aimed to summarize the first experience with ultrasound-guided percutaneous ablation treatment (PAT) for recurrent hepatoblastoma (HB) after liver resection in children. From August 2013 to October 2014, PAT was used to treat 5 children with a total of 8 recurrent HB (mean size, 1.4 ± 0.8 cm; size range, 0.7-3.1 cm), including 4 patients with 7 tumors in the liver and 1 patient with 1 tumor in the lung. Technical success was achieved in all patients (5/5, 100%). The complete ablation rate after the first ablation session was 80% (4/5) on a patient-by-patient basis and 87.5% (7/8) on a tumor-by-tumor basis. Only 1 patient developed a fever with temperature >39 °C; it lasted 4 days after radiofrequency ablation (RFA) and was resolved by conservative therapy. During the follow-up period, new intrahepatic recurrences after PAT were detected in two patients. One died due to tumor progression 4 months after ablation. The median overall survival time after PAT was 13.8 months. PAT is a safe and promising therapy for children with recurrent HB after liver resection, and further investigation in large-scale randomized clinical trials is required to determine its role in the treatment of this disease.

Related: Hepatoblastoma Liver Cancer Childhood Liver Cancer

Choi TW, Kim HC, Lee JH, et al.
The Safety and Clinical Outcomes of Chemoembolization in Child-Pugh Class C Patients with Hepatocellular Carcinomas.
Korean J Radiol. 2015 Nov-Dec; 16(6):1283-93 [PubMed] Article available free on PMC after 01/07/2017 Related Publications

OBJECTIVE: To evaluate the safety and clinical outcomes of chemoembolization in Child-Pugh class C patients with hepatocellular carcinomas (HCC).
MATERIALS AND METHODS: The study comprised 55 patients with HCC who were classified as Child-Pugh class C and who underwent initial chemoembolization between January 2003 and December 2012. Selective chemoembolization was performed in all technically feasible cases to minimize procedure-related complications. All adverse events within 30 days were recorded using the Common Terminology Criteria for Adverse Events (CTCAE). The tumor response to chemoembolization was evaluated using the modified Response Evaluation Criteria In Solid Tumors.
RESULTS: Thirty (54.5%) patients were within the Milan criteria, and 25 (45.5%) were beyond. The mortality of study subjects at 30 days was 5.5%. Major complications were observed in five (9.1%) patients who were all beyond the Milan criteria: two hepatic failures, one hepatic encephalopathy, and two CTCAE grade 3 increases in aspartate aminotransferase/alanine aminotransferase abnormality. The mean length of hospitalization was 6.3 ± 8.3 days (standard deviation), and 18 (32.7%) patients were discharged on the next day after chemoembolization. The tumor responses of the patients who met the Milan criteria were significantly higher (p = 0.014) than those of the patients who did not. The overall median survival was 7.1 months (95% confidence interval: 4.4-9.8 months).
CONCLUSION: Even in patients with Child-Pugh class C, chemoembolization can be performed safely with a selective technique in selected cases with a small tumor burden.

Related: Liver Cancer

Cai HY, Yu B, Feng ZC, et al.
Clinical significance of CD44 expression in children with hepatoblastoma.
Genet Mol Res. 2015; 14(4):13203-7 [PubMed] Related Publications

The aim of this study was to investigate the expression of CD44 and its clinical significance in children suffering from hepatoblastoma (HB). CD44 expression was detected with immunohistochemistry staining in 30 samples from hepatoblastoma children and 10 normal liver tissue samples from normal children. The data obtained was statistically analyzed using the chi-square test, using the SPSS (v.11.0) software. The rate of CD44 expression was significantly higher (66.7%) in hepatoblastoma tissues than in normal liver tissues (χ(2) = 4.848, P < 0.05). The rate of CD44 expression was significantly higher in children with stage III or IV hepatoblastoma (83.3%) than that in children with stage I and II hepatoblastoma (χ(2) ＝ 5.625, P < 0.05) (41.7%). Therefore, CD44 expression might play an important role in the pathogenesis, progression, and prognosis of HB in children.

Related: Hepatoblastoma Liver Cancer Childhood Liver Cancer

Bortel N, Armeanu-Ebinger S, Schmid E, et al.
Effects of curcumin in pediatric epithelial liver tumors: inhibition of tumor growth and alpha-fetoprotein in vitro and in vivo involving the NFkappaB- and the beta-catenin pathways.
Oncotarget. 2015; 6(38):40680-91 [PubMed] Article available free on PMC after 01/07/2017 Related Publications

In children with hepatocellular carcinoma (pHCC) the 5-year overall survival rate is poor. Effects of cytostatic therapies such as cisplatin and doxorubicin are limited due to chemoresistance and tumor relapse. In adult HCC, several antitumor properties are described for the use of curcumin. Curcumin is one of the best-investigated phytochemicals in complementary oncology without relevant side effects. Its use is limited by low bioavailability. Little is known about the influence of curcumin on pediatric epithelial hepatic malignancies. We investigated the effects of curcumin in combination with cisplatin on two pediatric epithelial liver tumor cell lines. As mechanisms of action inhibition of NFkappaB, beta-catenin, and decrease of cyclin D were identified. Using a mouse xenograft model we could show a significant decrease of alpha-fetoprotein after combination therapy of oral micellar curcumin and cisplatin. Significant concentrations of curcuminoids were found in blood samples, organ lysates, and tumor tissue after oral micellar curcumin administration. Micellar curcumin in combination with cisplatin can be a promising strategy for treatment of pediatric HCC.

Related: Apoptosis Liver Cancer Childhood Liver Cancer Angiogenesis and Cancer CTNNB1

Zimmermann E, Berentzen TL, Gamborg M, et al.
Sex-specific associations between birth weight and adult primary liver cancer in a large cohort of Danish children.
Int J Cancer. 2016; 138(6):1410-5 [PubMed] Related Publications

Whether the prenatal period is critical for the development of adult primary liver cancer (PLC) is sparsely investigated. Recently, attention has been drawn to potential sex-differences in the early origins of adult disease. The association between birth weight and adult PLC, separately in men and women was investigated, using a large cohort of 217,227 children (51% boys), born from 1936 to 1980, from the Copenhagen School Health Records Register, and followed them until 2010 in national registers. Hazard ratios (95% confidence intervals) of PLC (30 years or older) were estimated by Cox regression models stratified by birth cohort. During 5.1 million person-years of follow-up, 185 men and 65 women developed PLC. Sex modified the association between birth weight and adult PLC (p values for interaction = 0.0005). Compared with a sex-specific reference group of birth weights between 3.25 and 3.75 kg, men with birth weights between 2.00 and 3.25 kg and 3.75-5.50 kg, had HRs of 1.48 (1.06-2.05) and 0.85 (0.56-1.28), respectively. Among women the corresponding HRs were 1.71 (0.90-3.29) and 3.43 (1.73-6.82). Associations were similar for hepatocellular carcinoma only, across year of birth, and after accounting for diagnoses of alcohol-related disorders, viral hepatitis and biliary cirrhosis. Prenatal exposures influenced the risk of adult PLC, and the effects at the high birth weight levels appeared to be sex-specific. These findings underscore the importance of considering sex-specific mechanisms in the early origins of adult PLC.

Related: Liver Cancer Childhood Liver Cancer

Lautz TB, Shah SA, Superina RA
Hepatoblastoma in Children With Congenital Portosystemic Shunts.
J Pediatr Gastroenterol Nutr. 2016; 62(4):542-5 [PubMed] Related Publications

Two children developed hepatoblastoma concurrent with congenital portosystemic shunts (PSSs) (Abernethy malformations). Both underwent operative ligation of their PSSs. One received concurrent tumor resection, whereas the other was deemed initially unresectable and underwent biopsy followed by neoadjuvant chemotherapy. Although benign hepatic masses, such as focal nodular hyperplasia and nodular regenerative hyperplasia, are common in patients with Abernethy malformations, malignant tumors have also been documented and should always be considered in the differential diagnosis of a patient with a congenital PSS and a hepatic mass.

Related: Hepatoblastoma Liver Cancer

Zhou SJ, Zhang EL, Liang BY, et al.
Morphologic severity of cirrhosis determines the extent of liver resection in patients with hepatocellular carcinoma and Child-Pugh grade A cirrhosis.
J Surg Res. 2016; 200(2):444-51 [PubMed] Related Publications

BACKGROUND: Liver resection is the mainstay of treatment for patients with hepatocellular carcinoma and compensated cirrhosis. We investigated the relationship between the morphologic severity of cirrhosis and post-hepatectomy liver failure (PHLF) and evaluated the role of cirrhosis staging in determination of the extent limit for liver resection.
METHODS: The clinicopathologic data of 672 consecutive patients with Child-Pugh grade A liver function who underwent curative liver resection for hepatocellular carcinoma in Tongji Hospital from 2009 to 2013 were retrospectively reviewed. Severity of cirrhosis was staged morphologically and histologically. Risk factors for histologic cirrhosis and PHLF were analyzed. The extent limit of liver resection with reference to morphologic staging was studied.
RESULTS: Morphologic and histologic stages were significantly correlated (τ = 0.809, P < 0.001). Multivariate analysis showed that morphologic staging was the most crucial factor for histologic cirrhosis (odds ratio = 26.99, 95% confidence interval = 16.88-43.14, P < 0.001) and PHLF (odds ratio = 11.48, 95% confidence interval = 6.04-21.82, P < 0.001). The incidence of PHLF was high in patients with mild cirrhosis after resection of four or more liver segments (13.6%), those with moderate cirrhosis after major resection (38.1%), and those with severe cirrhosis or severe portal hypertension after resection of two or more liver segments (63.2% and 50.0%, respectively).
CONCLUSIONS: Morphologic severity of cirrhosis is an independent predictor of PHLF. Resection of fewer than four liver segments is justified in patients with mild cirrhosis. Major resection is not recommended in patients with moderate cirrhosis. In patients with severe cirrhosis or severe portal hypertension, only resection of fewer than two liver segments can be safely performed.

Related: Liver Cancer

Mirza W, McHugh K, Aslam M, et al.
CT Pelvis in Children; Should We Routinely Scan Pelvis for Wilms Tumor and Hepatoblastoma? Implications for Imaging Protocol Development.
J Coll Physicians Surg Pak. 2015; 25(10):768770-695 [PubMed] Related Publications

Wilms tumor and hepatoblastoma are the most common intra-abdominal solid organ childhood tumors. CT examination is one of the routinely performed procedures in hospitals for children with these tumors inspite of high radiation exposure associated with CT scans. Sixty patients (Wilms tumor = 45, hepatoblastoma = 16) were evaluated retrospectively. Higher proportion (44.4%) of metastatic disease was identified at presentation in the Wilms tumor subset as compared to hepatoblastoma (6.3%) [p=0.006]. Metastatic disease was noted in 6 patients having Wilms tumor on follow-up while it was also low in hepatoblastoma which was noted in only 2 patients (p > 0.05). No significant difference was identified in pelvic extension of disease at presentation in both studied population (p > 0.05). Pelvic metastasis was noted in 1 patient only with Wilms tumor on follow-up while no pelvic metastasis was seen in the hepatoblastoma patients (p-value > 0.05).

Related: Hepatoblastoma Kidney Cancer Liver Cancer Childhood Liver Cancer Wilms' Tumour Wilms Tumour

Pschierer K, Grothues D, Rennert J, et al.
Evaluation of the diagnostic accuracy of CEUS in children with benign and malignant liver lesions and portal vein anomalies.
Clin Hemorheol Microcirc. 2015; 61(2):333-45 [PubMed] Related Publications

OBJECTIVE: Comparison of the diagnostic findings of MRI, CT and CEUS in children with benign and malignant and portal venous anomalies of the liver.
MATERIALS/METHODS: Retrospective analysis of the diagnostic findings of CEUS, MRI and CT scans in 56 children (age 0-17 years) with a total of 60 benign and malignant liver lesions and anomalies of the portal vein/perfusion. All patients underwent CEUS using sulphur hexafluoride microbubbles and a multi-frequency probe (1-5 MHz, 6-9 MHz). Cine-loops were stored up to 3 minutes. MRI was performed in 38 lesions. CT was performed in 8 lesions.
RESULTS: Out of the 56 patients 49 liver lesions (48 benign, 1 malignant), 9 anomalies of the portal vein/perfusion and 2 of the biliary system were detected. 16/49 lesions were analyzed histopathologically. Using CEUS, the characterization of the lesions was possible in 45 out of 49 cases. In 32 cases, CEUS provided the exact diagnosis. Only two benign lesions were falsely categorized as malignant.Findings of MRI and CEUS were concordant in 84% of cases (n = 32/38). CEUS considered 1 benign lesion to be malignant. 2 lesions were not detectable and in 3 lesions no definite diagnosis was established using MRI.Findings of CT and CEUS were concordant in 5 of 8 cases. In 21 lesions CEUS as the only imaging modality was found to be sufficient for diagnostics.
CONCLUSION: Despite the restricted indications for using CEUS in children, it offers a high diagnostic detection rate (93%) for characterization of liver lesions and portal vein anomalies.

Related: Liver Cancer Childhood Liver Cancer

Qiao GL, Chen Z, Wang C, et al.
Pure fetal histology subtype was associated with better prognosis of children with hepatoblastoma: A Chinese population-based study.
J Gastroenterol Hepatol. 2016; 31(3):621-7 [PubMed] Related Publications

BACKGROUND AND AIM: The aim of this study is to identify the association between histologic types and the prognosis of hepatoblastoma (HB) in a large Asian cohort of a single institution and to explore the interaction of histologic types with other independently risk factors in the process of affecting prognosis of HB.
METHODS: We retrospectively reviewed 176 children with HB (82 female, 94 male) managed in our institution between May 1, 2001 and July 30, 2014. Prognostic factors were evaluated using Kaplan-Meier curves and Cox proportional hazards models.
RESULTS: For the entire cohort of 176 patients, the overall median survival was 80.4 months(95% CI: 71.6-89.2 months), and the 5-year event-free survival and overall survival rates were 54.6 and 66.7%. Descriptive survival statistics and Kaplan-Meier curves suggested that alpha fetoprotein levels, tumor metastases, multifocality, histologic types, and Pre-Treatment Extent of Disease staging System stage had prognostic significance in this relatively selected cohort. Moreover, after eliminating the impact of the interaction of different classification methods of histologic types, pure fetal histologic (PFH) was an independent prognostic factor of HB (hazard ratio [HR]: 2.752, P = 0.021). Further stratification analysis showed that the impaction of other identified risk factors on the influence of PFH on the prognosis of HB patients was different.
CONCLUSIONS: We have confirmed that the HB prognostic factors of HB and PFH was associated with better prognosis of children with HB based on an Asian population. PFH showed different significance in the process of affecting prognosis of HB with the interaction of other independent risk factors.

Related: Hepatoblastoma Liver Cancer Childhood Liver Cancer

Hiyama E, Hishiki T, Watanabe K, et al.
Mortality and morbidity in primarily resected hepatoblastomas in Japan: Experience of the JPLT (Japanese Study Group for Pediatric Liver Tumor) trials.
J Pediatr Surg. 2015; 50(12):2098-101 [PubMed] Related Publications

BACKGROUND: In the Japanese Study Group for Pediatric Liver Tumor (JPLT) protocols (JPLT-1 and 2) for evaluating the cure rate of risk-stratified hepatoblastoma, primary resection was permitted in PRETEXT I and II cases, followed by postoperative chemotherapy.
METHODS: In approximately 500 enrolled cases, resection was performed as the initial treatment in 60 cases, including all 18 PRETEXT I, 30 PRETEXT II, and 12 ruptured cases. The clinical features, surgical procedures, complications, and survival rates were compared in these three groups.
RESULTS: All 18 PRETEXT I cases underwent complete resection by lobectomy or segmentectomy (n=14) or nonanatomical partial hepatectomy (NPH) (n=4). The 30 PRETEXT II cases underwent primary resection by right or left lobectomy (n=16), NPH (n=10), or other procedures (n=4). Of these 30 cases, operational death occurred in 1 newborn, and recurrence occurred in 7 cases (14.6%), including 6 NPH cases and 4 older cases (aged >3years). Of the 12 ruptured cases, 7 (58.3%) showed recurrence. Event-free survival rates at 5years in the 3 groups were 88%, 70%, and 32%, respectively.
CONCLUSIONS: Primary resection for PRETEXT I or II HB cases should be performed by anatomical resection according to strict surgical guidelines. More intensified chemotherapy is required for primary resected cases whose tumors have ruptured.

Related: Hepatoblastoma Liver Cancer Childhood Liver Cancer

Pham TA, Gallo AM, Concepcion W, et al.
Effect of Liver Transplant on Long-term Disease-Free Survival in Children With Hepatoblastoma and Hepatocellular Cancer.
JAMA Surg. 2015; 150(12):1150-8 [PubMed] Related Publications

INTRODUCTION: Hepatoblastoma (HBL) and hepatocellular cancer (HCC) are the most common primary hepatic malignant neoplasms in childhood. Given the rarity of these childhood tumors and their propensity to present at advanced stages, updated long-term data are needed.
OBJECTIVE: To determine the efficacy of liver transplant in children with HBL or HCC.
DESIGN, PARTICIPANTS, AND SETTING: This single-institution retrospective medical record review and analysis spanned from January 1, 1997, through September 17, 2014, at Stanford University School of Medicine. A total of 40 patients younger than 18 years underwent liver transplant for treatment of HBL (n = 30) or HCC (n = 10) during the study period, with follow-up until September 17, 2014. Patients who underwent transplant for HCC included those with tumors that were greater in size than what is proposed by the Milan (a single tumor measuring ≤5 cm or ≤3 nodules measuring ≤3 cm) and University of California, San Francisco (single tumor measuring ≤6.5 cm or ≤3 nodules measuring ≤4.5 cm and a total diameter of ≤8 cm), criteria.
MAIN OUTCOMES AND MEASURES: Disease-free and overall patient survival and graft survival.
RESULTS: Using a Kaplan-Meier survival analysis, 1-, 5-, and 10-year disease-free survival after liver transplant was 93%, 82%, and 82%, respectively, for 30 patients with HBL and 90%, 78%, and 78%, respectively, for 10 patients with HCC. Risk factors associated with HBL recurrence after transplant included having pretreatment extent of disease stage IV lesions and a longer waiting list time and being older at the time of the transplant. Recurrence was found in 2 of 7 patients with HBL and pretransplant metastases, which were not found to be an independent risk factor for recurrence. Patients with HCC larger than the proposed Milan and University of California, San Francisco, criteria experienced good 5-year disease-free (82%) and overall (78%) survival after transplant. Being older at the time of transplant (18 vs 11 years; P = .04) and the presence of metastatic disease (1 patient vs none; P = .05) were associated with HCC tumor recurrence.
CONCLUSIONS AND RELEVANCE: Liver transplant combined with chemotherapy is an excellent treatment that provides long-term disease-free survival in children diagnosed with advanced HBL and HCC. Early addition to a waiting list and aggressive multimodal therapy provide excellent results. Transplant should still be considered in children with HCC larger than the Milan and University of California, San Francisco, criteria.

Related: Hepatoblastoma Liver Cancer Childhood Liver Cancer

Qureshi SS, Bhagat M, Kembhavi S, et al.
Benign liver tumors in children: outcomes after resection.
Pediatr Surg Int. 2015; 31(12):1145-9 [PubMed] Related Publications

PURPOSE: Benign liver tumors in children are rare and data regarding the surgical outcomes are deficient. We reviewed our experience in the management of these tumors particularly the extent, safety, and effectiveness of surgical resection.
METHODS: Between March 2005 and March 2014, 10/90 liver resections were performed for benign liver tumors. Three other patients received conservative treatment. Demographic characteristics, operative management, morbidity, and mortality were analyzed.
RESULTS: The median age of the patients was 12 months. The distribution of pathology was infantile hepatic hemangioendothelioma/hemangioma (n = 7), mesenchymal hamartoma (n = 4), adenoma (n = 1) and focal nodular hyperplasia (n = 1). Median tumor size was 12.25 cm (range 3.5-21 cm) with a median tumor volume of 576.64 cm(3) (range 13.9-1822.64 cm(3)). Non-anatomic resection was performed in 6/10 patients and the median blood loss was 100 ml (range 10-850 ml). Median length of hospital stay was 7 days (range 5-9 days). There were no mortality, none of the patients had a local recurrence, and all are alive at a median follow-up of 33 months.
CONCLUSIONS: Two-third patients with benign liver tumors were managed with surgical excision, which comprised 11% of our resectional practice. Non-anatomical resection whenever feasible can be performed safely and does not compromise the oncological outcomes.

Related: Liver Cancer

Chiorean L, Cui XW, Tannapfel A, et al.
Benign liver tumors in pediatric patients - Review with emphasis on imaging features.
World J Gastroenterol. 2015; 21(28):8541-61 [PubMed] Article available free on PMC after 01/07/2017 Related Publications

Benign hepatic tumors are commonly observed in adults, but rarely reported in children. The reasons for this remain speculative and the exact data concerning the incidence of these lesions are lacking. Benign hepatic tumors represent a diverse group of epithelial and mesenchymal tumors. In pediatric patients, most benign focal liver lesions are inborn and may grow like the rest of the body. Knowledge of pediatric liver diseases and their imaging appearances is essential in order to make an appropriate differential diagnosis. Selection of the appropriate imaging test is challenging, since it depends on a number of age-related factors. This paper will discuss the most frequently encountered benign liver tumors in children (infantile hepatic hemangioendothelioma, mesenchymal hamartoma, focal nodular hyperplasia, nodular regenerative hyperplasia, and hepatocellular adenoma), as well as a comparison to the current knowledge regarding such tumors in adult patients. The current emphasis is on imaging features, which are helpful not only for the initial diagnosis, but also for pre- and post-treatment evaluation and follow-up. In addition, future perspectives of contrast-enhanced ultrasound (CEUS) in pediatric patients are highlighted, with descriptions of enhancement patterns for each lesion being discussed. The role of advanced imaging tests such as CEUS and magnetic resonance imaging, which allow for non-invasive assessment of liver tumors, is of utmost importance in pediatric patients, especially when repeated imaging tests are needed and radiation exposure should be avoided.

Related: Liver Cancer Childhood Liver Cancer

Tannuri AC, Cristofani LM, Teixeira RA, et al.
New concepts and outcomes for children with hepatoblastoma based on the experience of a tertiary center over the last 21 years.
Clinics (Sao Paulo). 2015; 70(6):387-92 [PubMed] Article available free on PMC after 01/07/2017 Related Publications

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.

Related: Cisplatin Doxorubicin Hepatoblastoma Liver Cancer Childhood Liver Cancer

Takeyama E, Tanaka M, Fujishiro J, et al.
A case of alpha-fetoprotein-producing gastric cancer in a child presenting with rupture of multiple liver metastases.
Pediatr Surg Int. 2015; 31(9):885-8 [PubMed] Related Publications

We report a 14-year-old boy with alpha-fetoprotein-producing gastric cancer (AFPGC) who was found with ruptured metastatic tumor in the liver. AFPGC is exceedingly rare in pediatric age. It often shows metastases to the liver and should be included in differential diagnoses of liver tumors with increased serum AFP.

Related: Stomach Cancer Gastric Cancer

Guo X, Li Q, Zhu YP
Childhood Hepatosplenic T-cell Lymphoma with Skin Involvement.
Indian Pediatr. 2015; 52(5):427-8 [PubMed] Related Publications

BACKGROUND: Hepatosplenic T-cell lymphoma is a rare malignancy in childhood.
CASE CHARACTERISTICS: A 12-year-old boy who presented a pyrexia of unknown origin, multiple skin and lesions and marked hepatosplenomegaly.
OBSERVATION: Bone marrow aspirate cytology showed no blast cells. Splenectomy was done, and spleen showed infiltration with atypical lymphoid cells positive for CD3, CD8 and T-cell-restricted intracellular antigen.
OUTCOME: The skin rash of patient subsided with chemotherapy.
MESSAGE: Skin involvement may be an unusual clinical manifestation of hepatosplenic T-cell lymphoma.

Related: Liver Cancer Childhood Liver Cancer

Millar AJ
Liver tumours in children: current surgical management and role of transplantation.
S Afr Med J. 2014; 104(11 Pt 2):813-5 [PubMed] Related Publications

This article reviews the current surgical management of liver tumours in children in the light of improved chemotherapy, surgical techniques and outcomes from transplantation. It is a principle of management that complete removal of a tumour must be achieved for cure. Neoadjuvant chemotherapy may downstage advanced local disease to enable safe curative tumour resection. When this is not achievable, transplant is indicated. Conventional indications for transplant are unresectable stages 3 and 4 tumours confined to the liver. With the realisation that lifelong immunosuppressive therapy has considerable adverse consequences, there has been a recent trend towards extreme and 'acrobatic' liver resection to avoid transplantation, but still obtain a cure. The current literature is reviewed in the light of these trends and our own experience.

Related: Liver Cancer Childhood Liver Cancer

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