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Nousiainen R, Eloranta K, Saarela J, Hassinen A, Luck TJ, Cairo S, Indersie E, Potdar S, Feodoroff MJ, Lohi J, Paavolainen L, Wilson DB, Pietiäinen V, Heikinheimo M, Pihlajoki M. Functional screening identifies kinesin spindle protein inhibitor filanesib as a potential treatment option for hepatoblastoma. NPJ Precis Oncol 2025; 9:122. [PMID: 40281281 PMCID: PMC12032252 DOI: 10.1038/s41698-025-00915-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2024] [Accepted: 04/15/2025] [Indexed: 04/29/2025] Open
Abstract
Hepatoblastoma is a rare pediatric liver malignancy usually treated with surgery and chemotherapy. To explore new treatment options for hepatoblastoma, drug screening was performed using six cell models established from aggressive hepatoblastoma tumors and healthy pediatric primary hepatocytes. Of the 527 screened compounds, 98 demonstrated cancer-selective activity in at least one hepatoblastoma model. The kinesin spindle protein (KSP) inhibitor filanesib was effective in all models and was further evaluated. Filanesib induced G2/M arrest and apoptosis in hepatoblastoma cells at concentrations tolerable to primary hepatocytes. Prominent nuclear fragmentation was observed in filanesib-treated hepatoblastoma cells. Genes participating in cell cycle regulation were noted to be differentially expressed after filanesib treatment. Filanesib reduced the rate of tumor growth in 4/5 hepatoblastoma mice models. One of these models showed complete growth arrest. Our results suggest that filanesib is a potential candidate for hepatoblastoma treatment and should be investigated in future clinical trials.
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Affiliation(s)
- Ruth Nousiainen
- Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland
- iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki, Finland
| | - Katja Eloranta
- Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
- Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland.
- iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki, Finland.
| | - Jani Saarela
- Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland
| | - Antti Hassinen
- Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland
| | - Tamara J Luck
- Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland
- iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki, Finland
| | - Stefano Cairo
- XenTech, Evry, France
- Champions Oncology, Hackensack, NJ, USA
- Istituto di Ricerca Pediatrica, Padova, Italy
| | | | - Swapnil Potdar
- Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland
| | - Michaela J Feodoroff
- Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland
- iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki, Finland
| | - Jouko Lohi
- Department of Pathology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Lassi Paavolainen
- Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland
- iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki, Finland
| | - David B Wilson
- Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, USA
- Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA
| | - Vilja Pietiäinen
- Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland
- iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki, Finland
| | - Markku Heikinheimo
- Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA
- Faculty of Medicine and Health Technology, Center for Child, Adolescent, and Maternal Health Research, Tampere University, Tampere, Finland
| | - Marjut Pihlajoki
- Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
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Lee S, Jeon H, Han J, Song IK, Baek SH, Shim S, Eun H, Park MS, Jang H, Shin JE, Ihn K. Management of Neonatal Hepatic Hemangiomas: A Single-Center Experience Focused on Challenging Cases. J Clin Med 2024; 13:2839. [PMID: 38792380 PMCID: PMC11122465 DOI: 10.3390/jcm13102839] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2024] [Revised: 05/07/2024] [Accepted: 05/08/2024] [Indexed: 05/26/2024] Open
Abstract
Background: Management of hepatic hemangioma (HH) in infancy ranges from close monitoring to surgical resection. We analyzed the clinical characteristics and outcomes of HH according to its treatment options, with particular focus on challenging cases. Methods: Data of patients diagnosed with HHs in their first year of life and followed up for at least 1 year were retrospectively reviewed and divided into treatment and observation groups. Serial imaging results, serum alpha-fetoprotein (AFP) levels, medications, and clinical outcomes were compared. The detailed clinical progress in the treatment group was reviewed separately. Results: A total of 87 patients (75 in the observation group and 12 in the treatment group) were included. The median HH size at the initial diagnosis and the maximum size were significantly larger in the treatment group than the observation group (2.2 [0.5-10.3] cm vs. 1.0 [0.4-4.0] cm and 2.1 [0.7-13.2] vs. 1.1 [0.4-4.0], respectively; all p < 0.05]. The median initial and last serum AFP levels were significantly higher in the treatment group than in the observation group (76,818.7 vs. 627.2 and 98.4 vs. 8.7, respectively; all p < 0.05). Serum AFP levels in both groups rapidly declined during the first 3 months of life and were almost undetectable after 6 months. Among the challenging cases, a large (14 × 10 × 6.5 cm sized) focal HH was successfully treated using stepwise medical-to-surgical treatment. Conclusions: Patients with large HH and mild symptoms can be treated using stepwise pharmacotherapy. More aggressive surgical treatment of tumors unresponsive to initial pharmacotherapy may help shorten the treatment period and improve outcomes.
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Affiliation(s)
- Sumin Lee
- Division of Neonatology, Department of Pediatrics, Severance Children’s Hospital, Yonsei University College of Medicine, Seoul 03722, Republic of Korea; (S.L.); (J.H.); (I.-K.S.); (S.H.B.); (S.S.); (H.E.); (M.S.P.)
| | - Hojong Jeon
- Division of Pediatric Surgery, Department of Surgery, National Health Insurance Service Ilsan Hospital, Goyang-si 10444, Republic of Korea;
| | - Jungho Han
- Division of Neonatology, Department of Pediatrics, Severance Children’s Hospital, Yonsei University College of Medicine, Seoul 03722, Republic of Korea; (S.L.); (J.H.); (I.-K.S.); (S.H.B.); (S.S.); (H.E.); (M.S.P.)
| | - In-Kyu Song
- Division of Neonatology, Department of Pediatrics, Severance Children’s Hospital, Yonsei University College of Medicine, Seoul 03722, Republic of Korea; (S.L.); (J.H.); (I.-K.S.); (S.H.B.); (S.S.); (H.E.); (M.S.P.)
| | - Seung Hwan Baek
- Division of Neonatology, Department of Pediatrics, Severance Children’s Hospital, Yonsei University College of Medicine, Seoul 03722, Republic of Korea; (S.L.); (J.H.); (I.-K.S.); (S.H.B.); (S.S.); (H.E.); (M.S.P.)
| | - Sungbo Shim
- Division of Neonatology, Department of Pediatrics, Severance Children’s Hospital, Yonsei University College of Medicine, Seoul 03722, Republic of Korea; (S.L.); (J.H.); (I.-K.S.); (S.H.B.); (S.S.); (H.E.); (M.S.P.)
| | - Hoseon Eun
- Division of Neonatology, Department of Pediatrics, Severance Children’s Hospital, Yonsei University College of Medicine, Seoul 03722, Republic of Korea; (S.L.); (J.H.); (I.-K.S.); (S.H.B.); (S.S.); (H.E.); (M.S.P.)
| | - Min Soo Park
- Division of Neonatology, Department of Pediatrics, Severance Children’s Hospital, Yonsei University College of Medicine, Seoul 03722, Republic of Korea; (S.L.); (J.H.); (I.-K.S.); (S.H.B.); (S.S.); (H.E.); (M.S.P.)
| | - Hyeonguk Jang
- Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
| | - Jeong Eun Shin
- Division of Neonatology, Department of Pediatrics, Severance Children’s Hospital, Yonsei University College of Medicine, Seoul 03722, Republic of Korea; (S.L.); (J.H.); (I.-K.S.); (S.H.B.); (S.S.); (H.E.); (M.S.P.)
| | - Kyong Ihn
- Division of Pediatric Surgery, Department of Surgery, Severance Children’s Hospital, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
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Ruan W, Galvan NTN, Dike P, Koci M, Faraone M, Fuller K, Koomaraie S, Cerminara D, Fishman DS, Deray KV, Munoz F, Schackman J, Leung D, Akcan-Arikan A, Virk M, Lam FW, Chau A, Desai MS, Hernandez JA, Goss JA. The Multidisciplinary Pediatric Liver Transplant. Curr Probl Surg 2023; 60:101377. [PMID: 37993242 DOI: 10.1016/j.cpsurg.2023.101377] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Accepted: 08/29/2023] [Indexed: 11/24/2023]
Affiliation(s)
- Wenly Ruan
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston, TX
| | - Nhu Thao N Galvan
- Division of Abdominal Transplantation, Michael E. DeBakey Department of Surgery, Department of Pediatric Surgery, Texas Children's Hospital, Baylor College of Medicine, Houston, TX.
| | - Peace Dike
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston, TX
| | - Melissa Koci
- Division of Abdominal Transplantation, Michael E. DeBakey Department of Surgery, Department of Pediatric Surgery, Texas Children's Hospital, Baylor College of Medicine, Houston, TX
| | - Marielle Faraone
- Baylor College of Medicine, Texas Children's Hospital, Houston, TX
| | - Kelby Fuller
- Baylor College of Medicine, Texas Children's Hospital, Houston, TX
| | | | - Dana Cerminara
- Department of Pharmacy, Texas Children's Hospital, Houston, TX
| | - Douglas S Fishman
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston, TX
| | - Kristen Valencia Deray
- Department of Pediatrics, Department of Pharmacy, Baylor College of Medicine, Texas Children's Hospital, Houston, TX
| | - Flor Munoz
- Department of Pediatrics, Department of Pharmacy, Baylor College of Medicine, Texas Children's Hospital, Houston, TX
| | - Julie Schackman
- Division of Anesthesiology, Perioperative, & Pain Medicine, Department of Anesthesiology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX
| | - Daniel Leung
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston, TX
| | - Ayse Akcan-Arikan
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston, TX
| | - Manpreet Virk
- Division of Critical Care, Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston, TX
| | - Fong W Lam
- Division of Critical Care, Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston, TX
| | - Alex Chau
- Division of Interventional Radiology, Department of Radiology, Edward B. Singleton Department of Radiology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX
| | - Moreshwar S Desai
- Division of Critical Care, Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston, TX
| | - Jose A Hernandez
- Division of Interventional Radiology, Department of Radiology, Edward B. Singleton Department of Radiology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX
| | - John A Goss
- Division of Abdominal Transplantation, Michael E. DeBakey Department of Surgery, Department of Pediatric Surgery, Texas Children's Hospital, Baylor College of Medicine, Houston, TX
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Pihlajoki M, Eloranta K, Nousiainen R, Väyrynen V, Soini T, Kyrönlahti A, Parkkila S, Kanerva J, Wilson DB, Pakarinen MP, Heikinheimo M. Biology of childhood hepatoblastoma and the search for novel treatments. Adv Biol Regul 2023; 91:100997. [PMID: 39492287 DOI: 10.1016/j.jbior.2023.100997] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2023] [Accepted: 10/17/2023] [Indexed: 11/05/2024]
Abstract
Our research laboratory has a longstanding interest in developmental disorders and embryonic tumors, and recent efforts have focused on the pathogenesis of pediatric liver tumors. This review focuses on hepatoblastoma (HB), the most common pediatric liver malignancy. Despite advances in treatment, patients with metastatic HB have a poor prognosis, and survivors often have permanent side effects attributable to chemotherapy. In an effort to improve survival and lessen long-term complications of HB, we have searched for novel molecular vulnerabilities using a combination of patient derived cell lines, metabolomics, and RNA sequencing of human samples at diagnosis and follow-up. These studies have shed light on pathogenesis and identified putative targets for future therapies in children with advanced HB.
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Affiliation(s)
- Marjut Pihlajoki
- Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
| | - Katja Eloranta
- Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Ruth Nousiainen
- Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Ville Väyrynen
- Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Tea Soini
- Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Antti Kyrönlahti
- Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Seppo Parkkila
- Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; FICAN Mid, Tampere University, Tampere, Finland; Fimlab Ltd, Tampere University Hospital, Tampere, Finland
| | - Jukka Kanerva
- Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - David B Wilson
- Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, United States; Department of Pediatrics, Washington University in St. Louis, St. Louis, United States
| | - Mikko P Pakarinen
- Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Section of Pediatric Surgery, Pediatric Liver and Gut Research Group, Pediatric Research Department of Women's Health, Karolinska Institute, Stockholm, Sweden
| | - Markku Heikinheimo
- Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Pediatrics, Washington University in St. Louis, St. Louis, United States; Faculty of Medicine and Health Technology, Center for Child, Adolescent, and Maternal Health Research, Tampere University, Tampere, Finland
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Zhu Q, Hu Y, Jiang W, Ou ZL, Yao YB, Zai HY. Circ-CCT2 Activates Wnt/β-catenin Signaling to Facilitate Hepatoblastoma Development by Stabilizing PTBP1 mRNA. Cell Mol Gastroenterol Hepatol 2023; 17:175-197. [PMID: 37866478 PMCID: PMC10758885 DOI: 10.1016/j.jcmgh.2023.10.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Revised: 10/13/2023] [Accepted: 10/13/2023] [Indexed: 10/24/2023]
Abstract
BACKGROUND & AIMS Circ-CCT2 (hsa_circ_0000418) is a novel circular RNA that stems from the CCT2 gene. However, the expression of circ-CCT2 and its roles in hepatoblastoma are unknown. Our study aims to study the circ-CCT2 roles in hepatoblastoma development. METHODS Hepatoblastoma specimens were collected for examining the expression of circ-CCT2, TAF15, and PTBP1. CCK-8 and colony formation assays were applied for cell proliferation analysis. Migratory and invasive capacities were evaluated through wound healing and Transwell assays. The interaction between circ-CCT2, TAF15, and PTBP1 was validated by fluorescence in situ hybridization, RNA pull-down, and RNA immunoprecipitation. SKL2001 was used as an agonist of the Wnt/β-catenin pathway. A subcutaneous mouse model of hepatoblastoma was established for examining the function of circ-CCT2 in hepatoblastoma in vivo. RESULTS Circ-CCT2 was significantly up-regulated in hepatoblastoma. Overexpression of circ-CCT2 activated Wnt/β-catenin signaling and promoted hepatoblastoma progression, whereas knockdown of circ-CCT2 exerted opposite effects. Moreover, both TAF15 and PTBP1 were up-regulated in hepatoblastoma tissues and cells. TAF15 was positively correlated with the expression of circ-CCT2 and PTBP1 in hepatoblastoma. Furthermore, circ-CCT2 recruited and up-regulated TAF15 protein to stabilize PTBP1 mRNA and trigger Wnt/β-catenin signaling in hepatoblastoma. Overexpression of TAF15 or PTBP1 reversed knockdown of circ-CCT2-mediated suppression of hepatoblastoma progression. SKL2001-mediated activation of Wnt/β-catenin signaling reversed the anti-tumor effects of silencing of circ-CCT2, TAF15, or PTBP1. CONCLUSIONS Circ-CCT2 stabilizes PTBP1 mRNA and activates Wnt/β-catenin signaling through recruiting and up-regulating TAF15 protein, thus promoting hepatoblastoma progression. Our findings deepen the understanding of hepatoblastoma pathogenesis and suggest potential therapeutic targets.
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Affiliation(s)
- Qin Zhu
- Department of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan Province, P.R. China
| | - Yu Hu
- Department of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan Province, P.R. China
| | - Wei Jiang
- Department of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan Province, P.R. China
| | - Zheng-Lin Ou
- Department of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan Province, P.R. China
| | - Yuan-Bing Yao
- Department of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan Province, P.R. China
| | - Hong-Yan Zai
- Department of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan Province, P.R. China.
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Li P, Kong Y, Guo J, Ji X, Han X, Zhang B. Incidence and trends of hepatic cancer among children and adolescents in the United States from 2000 to 2017: Evidence from the Surveillance, Epidemiology, and End Results registry data. Cancer Causes Control 2023; 34:69-79. [PMID: 36244051 DOI: 10.1007/s10552-022-01640-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Accepted: 10/03/2022] [Indexed: 01/10/2023]
Abstract
OBJECTIVE Primary liver tumors are rare pediatric malignancies. Knowledge of the epidemiology of pediatric liver tumors is limited. This study aims to present the national incidence trends of pediatric liver tumors over 18 years, according to sociodemographic and histological subtype variation. METHODS The Surveillance, Epidemiology, and End Results registry was queried from 2000 to 2017 for 1,099 patients between ages 0 and 19 with liver tumors. Age-standardized incidence rates by age, sex, and race/ethnicity were examined among histological subtypes. Annual percentage change (APC) was calculated via joinpoint regression for various sociodemographic and histotype subgroups. RESULTS An increase of age-adjusted incidence rate of pediatric hepatic cancers was observed between 2000 and 2017 (APC, 1.7% [95% confidence interval or CI: 0.6%-2.8%], p-value = 0.006), which may likely attribute to the increasing incidence of hepatoblastoma and mesenchymal tumors (APC, 2.5% [95% CI: 1.1%-3.8%], p-value = 0.001). The incidence trend of hepatocellular carcinoma remained stable in the study period. The non-Hispanic Asian/Pacific Islander children and adolescents had a higher risk of hepatic tumors (incidence rate ratio or IRR, 1.42 [95% CI: 1.16-1.72], p-value = 0.0007) when compared with the non-Hispanic white subgroup, while a non-Hispanic black child was associated with a lower incidence rate (IRR, 0.64 [95% CI: 0.50-0.80], p-value < 0.0001). Significantly lower hepatic tumor incidence occurred in females than males, with an incidence rate ratio of 0.69 (95% CI: 0.61-0.78; p-value < 0.0001). Hepatic tumor incidence was also significantly lower in those aged 1-4 years (IRR, 0.47 [95% CI: 0.40-0.54]; p-value < 0.001) and 5-19 years (IRR, 0.09 [95% CI: 0.08-0.10]; p-value < 0.001) when compared with the youngest age group aged less than 1 year. These significant differences were also detected for the subgroup of hepatoblastoma and mesenchymal liver tumors but less among hepatocellular carcinomas (all p-values less than 0.0001). CONCLUSION Continued increasing incidence of pediatric hepatoblastoma and mesenchymal liver tumors was discovered and warranted further investigation. Additional findings include a lower incidence of hepatic cancer among non-Hispanic black individuals and higher incidence of hepatic cancer in non-Hispanic Asian/Pacific Islander, male, and aged 1-4-year children and adolescents.
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Affiliation(s)
- Peiyi Li
- Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.,Laboratory of Anesthesia and Critical Care Medicine, National-Local Joint Engineering Research Centre of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.,The Research Units of West China (2018RU012), Chinese Academy of Medical Sciences, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Yujia Kong
- Department of Public Health, Weifang Medical University, Weifang, Shandong, China
| | - Jing Guo
- Department of Health Policy and Management, School of Public Health, Peking University, Beijing, China
| | - Xu Ji
- Department of Pediatrics, Emory University School of Medicine/Aflac Cancer & Blood Disorders Center, Children's Healthcare of Atlanta, Atlanta, GA, USA
| | - Xuesong Han
- Surveillance and Health Equity Science, American Cancer Society, Atlanta, GA, USA
| | - Bo Zhang
- Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. .,Biostatistics and Research Design Center, Institutional Centers for Clinical and Translational Research, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
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Xing H, Yang C, Tan B, Zhang M. Competitive risk analysis of the therapeutic value of liver transplantation for liver cancer in children: A population-based study. Front Surg 2022; 9:938254. [PMID: 36117822 PMCID: PMC9470878 DOI: 10.3389/fsurg.2022.938254] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2022] [Accepted: 08/01/2022] [Indexed: 11/13/2022] Open
Abstract
BackgroundLiver transplantation (LT) is one of the most important treatments for children with liver cancer (CLCa) and has been increasingly used. However, there is a lack of large-scale and multicenter studies on the trend in the application and value of LT for the treatment of CLCa.MethodsWe analyzed the clinicopathological data of CLCa from 2000 to 2018 from the Surveillance, Epidemiology, and End Results (SEER) database. We explored the trend in the application of LT for the treatment of CLCa. LASSO Cox regression and the Log-Rank test were used to explore prognostic factors, and we built a nomogram using the screened factors. Propensity score matching was used to balance the baseline data of patients undergoing LT and other surgeries, and then the Log-Rank test was used to evaluate the therapeutic value of LT for CLCa.ResultsThe 1-year, 3-year, 5-year, and 10-year overall survival (OS) rates of CLCa were 88.7%, 80.6%, 76.8%, and 73.0%, respectively. Then, we established a nomogram using many variables including age of diagnosis, regional lymph node metastasis, summary stage, and therapy. Internally validated and externally verified, our nomogram had good predictive power and clinical applicability. LT was increasingly being used to treat CLCa. There was no statistically significant difference in the OS of CLCa between the LT and other surgeries groups. After LT, the hepatoblastoma group had a better prognosis than the hepatocellular carcinoma group.ConclusionWe built a well-performing nomogram to predict the OS of CLCa. LT could improve the prognosis of CLCa as other surgeries and could be considered an effective treatment choice for CLCa.
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Falqueto LE, Vilar PR, Campos HG, Schulz C, Mattos E Silva EDE. Primary Malignant Liver Tumors: eight-year experience in a Pediatric Hospital in Brazil. A cross-sectional study. Rev Col Bras Cir 2022; 49:e20223273. [PMID: 35703678 PMCID: PMC10578837 DOI: 10.1590/0100-6991e-20223273-en] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Accepted: 03/22/2022] [Indexed: 11/21/2022] Open
Abstract
INTRODUCTION liver tumors are rare neoplasms in childhood (1-2%), and about 2/3 are malignant. Hepatoblastoma (HB) is the most frequent, followed by hepatocellular carcinoma (HCC). In both, the main treatment is surgical resection. Currently, chemotherapy and liver transplantation have improved outcomes. OBJECTIVE study of the epidemiological profile and evolution of liver cancer cases in a referral pediatric hospital. METHODOLOGY a retrospective survey of medical records of patients aged up to 18 years with a diagnosis of primary malignant hepatic neoplasm between 2012 and 2020, carried out in the largest exclusively pediatric hospital in Brazil. RESULTS a total of 13 patients with malignant liver tumors (HB 12, HCC 1) were treated. Of the HB cases, 66,7% were male, with a mean age of 2 years and the main alteration in the palpable abdominal mass. Tumors involved an average of 3 liver segments, more in the right lobe (54%). Only one patient was treated with surgery without neoadjuvant therapy, another one underwent transplantation like the first treatment, and another 2 required liver transplantation as a rescue. The middle follow-up time of patients with HB was 39 months and only 1 case died due to febrile neutropenia. The 5-year overall and disease-free survival was 91.7% and 81.5%, respectively. CONCLUSION Advanced staging at the time of diagnosis has always been a poor prognostic factor in patients with primary malignant liver tumors. However, the results and survival have improved with the advancement of chemotherapy, surgical technique, and liver transplantation.
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Affiliation(s)
| | - Paula Rubio Vilar
- - Hospital Pequeno Príncipe, Cirurgia Pediátrica - Curitiba - PR - Brasil
| | | | - Claudio Schulz
- - Hospital Pequeno Príncipe, Cirurgia Pediátrica - Curitiba - PR - Brasil
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Moreira-Silva H, Amorim J, Santos-Silva E. Incidental Liver Lesions in children: A practical and evidence-based approach. Clin Res Hepatol Gastroenterol 2022; 46:101904. [PMID: 35318140 DOI: 10.1016/j.clinre.2022.101904] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2021] [Revised: 02/19/2022] [Accepted: 02/24/2022] [Indexed: 02/04/2023]
Abstract
Incidental liver lesions are increasingly being discovered in the context of the increased use of ultrasound studies and the majority are benign. In children, although individually rare, the differential diagnosis is broad and therefore a systematic approach is of utmost importance to reduce the radiological and disease burden in children and their families. This review article collected current evidence and provides fundamental information for the clinician regarding specific differential diagnoses and unique imaging features of benign liver lesions in children. Ultimately, we propose a practical stepwise approach mainly involving clinical and radiological workup. Laboratory tests and histopathological examination may be necessary in the presence of red flags or in indeterminate lesions.
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Affiliation(s)
- Helena Moreira-Silva
- Pediatric Gastroenterology Unit, Centro Materno Infantil do Norte, Centro Hospitalar Universitário do Porto, Largo da Maternidade de Júlio Dinis 45, Porto 4050-651, Portugal.
| | - João Amorim
- Radiology Department, Centro Materno Infantil do Norte, Centro Hospitalar Universitário do Porto, Porto, Portugal
| | - Ermelinda Santos-Silva
- Pediatric Gastroenterology Unit, Centro Materno Infantil do Norte, Centro Hospitalar Universitário do Porto, Largo da Maternidade de Júlio Dinis 45, Porto 4050-651, Portugal
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10
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Klunder MB, Bruggink JLM, Huynh LDH, Bodewes FAJA, van der Steeg AFW, Kraal KCJM, van de Ven CP(K, van Grotel M, Zsiros J, Wijnen MHWA, Molenaar IQ(Q, Porte RJ, de Meijer VE, de Kleine RH. Surgical Outcome of Children with a Malignant Liver Tumour in The Netherlands: A Retrospective Consecutive Cohort Study. CHILDREN (BASEL, SWITZERLAND) 2022; 9:children9040525. [PMID: 35455569 PMCID: PMC9028819 DOI: 10.3390/children9040525] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/27/2022] [Revised: 04/02/2022] [Accepted: 04/04/2022] [Indexed: 11/16/2022]
Abstract
Introduction: Six to eight children are diagnosed with a malignant liver tumour yearly in the Netherlands. The majority of these tumours are hepatoblastoma (HB) and hepatocellular carcinoma (HCC), for which radical resection, often in combination with chemotherapy, is the only curative treatment option. We investigated the surgical outcome of children with a malignant liver tumour in a consecutive cohort in the Netherlands. Methods: In this nationwide, retrospective observational study, all patients (age < 18 years) diagnosed with a malignant liver tumour, who underwent partial liver resection or orthotopic liver transplantation (OLT) between January 2014 and April 2021, were included. Children with a malignant liver tumour who were not eligible for surgery were excluded from the analysis. Data regarding tumour characteristics, diagnostics, treatment, complications and survival were collected. Outcomes included major complications (Clavien−Dindo ≥ 3a) within 90 days and disease-free survival. The results of the HB group were compared to those of a historical HB cohort. Results: Twenty-six children were analysed, of whom fourteen (54%) with HB (median age 21.5 months), ten (38%) with HCC (median age 140 months) and one with sarcoma and a CNSET. Thirteen children with HB (93%) and three children with HCC (30%) received neoadjuvant chemotherapy. Partial hepatic resection was possible in 19 patients (12 HB, 6 HCC, and 1 sarcoma), whilst 7 children required OLT (2 HB, 4 HCC, and 1 CNSET). Radical resection (R0, margin ≥ 1.0 mm) was obtained in 24 out of 26 patients, with recurrence only in the patient with CNSET. The mean follow-up was 39.7 months (HB 40 months, HCC 40 months). Major complications occurred in 9 out of 26 patients (35% in all, 4 of 14, 29% for HB). There was no 30- or 90-day mortality, with disease-free survival after surgery of 100% for HB and 80% for HCC, respectively. Results showed a tendency towards a better outcome compared to the historic cohort, but numbers were too small to reach significance. Conclusion: Survival after surgical treatment for malignant liver tumours in the Netherlands is excellent. Severe surgical complications arise in one-third of patients, but most resolve without long-term sequelae and have no impact on long-term survival.
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Affiliation(s)
- Merel B. Klunder
- Department of Surgery, Division of Hepato-Pancreatico-Biliary Surgery and Liver Transplantation, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands; (M.B.K.); (R.J.P.); (V.E.d.M.)
| | - Janneke L. M. Bruggink
- Department of Surgery, Division of Pediatric Surgery, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands;
| | - Leon D. H. Huynh
- Department of Surgery, Princess Máxima Center for Pediatric Oncology, 2584 CS Utrecht, The Netherlands; (L.D.H.H.); (A.F.W.v.d.S.); (C.P.v.d.V.); (M.H.W.A.W.)
| | - Frank A. J. A. Bodewes
- Department of Pediatric Hepatology and Gastroenterology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands;
| | - Alida F. W. van der Steeg
- Department of Surgery, Princess Máxima Center for Pediatric Oncology, 2584 CS Utrecht, The Netherlands; (L.D.H.H.); (A.F.W.v.d.S.); (C.P.v.d.V.); (M.H.W.A.W.)
| | - Kathelijne C. J. M. Kraal
- Department of Pediatric Oncology, Princess Máxima Center for Pediatric Oncology, 2584 CS Utrecht, The Netherlands; (K.C.J.M.K.); (M.v.G.); (J.Z.)
| | - C. P. (Kees) van de Ven
- Department of Surgery, Princess Máxima Center for Pediatric Oncology, 2584 CS Utrecht, The Netherlands; (L.D.H.H.); (A.F.W.v.d.S.); (C.P.v.d.V.); (M.H.W.A.W.)
| | - Martine van Grotel
- Department of Pediatric Oncology, Princess Máxima Center for Pediatric Oncology, 2584 CS Utrecht, The Netherlands; (K.C.J.M.K.); (M.v.G.); (J.Z.)
| | - József Zsiros
- Department of Pediatric Oncology, Princess Máxima Center for Pediatric Oncology, 2584 CS Utrecht, The Netherlands; (K.C.J.M.K.); (M.v.G.); (J.Z.)
| | - Marc H. W. A. Wijnen
- Department of Surgery, Princess Máxima Center for Pediatric Oncology, 2584 CS Utrecht, The Netherlands; (L.D.H.H.); (A.F.W.v.d.S.); (C.P.v.d.V.); (M.H.W.A.W.)
| | - I. Q. (Quintus) Molenaar
- Department of Surgery, University of Utrecht, University Medical Center Utrecht, 2584 CX Utrecht, The Netherlands;
| | - Robert J. Porte
- Department of Surgery, Division of Hepato-Pancreatico-Biliary Surgery and Liver Transplantation, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands; (M.B.K.); (R.J.P.); (V.E.d.M.)
| | - Vincent E. de Meijer
- Department of Surgery, Division of Hepato-Pancreatico-Biliary Surgery and Liver Transplantation, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands; (M.B.K.); (R.J.P.); (V.E.d.M.)
| | - Ruben H. de Kleine
- Department of Surgery, Division of Hepato-Pancreatico-Biliary Surgery and Liver Transplantation, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands; (M.B.K.); (R.J.P.); (V.E.d.M.)
- Correspondence:
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11
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Hishiki T, Honda S, Takama Y, Inomata Y, Okajima H, Hoshino K, Suzuki T, Souzaki R, Wada M, Kasahara M, Mizuta K, Oue T, Yokoi A, Kazama T, Komatsu S, Saeki I, Miyazaki O, Takimoto T, Ida K, Watanabe K, Hiyama E. Feasibility of Real-Time Central Surgical Review for Patients with Advanced-Stage Hepatoblastoma in the JPLT3 Trial. CHILDREN (BASEL, SWITZERLAND) 2022; 9:children9020234. [PMID: 35204954 PMCID: PMC8870682 DOI: 10.3390/children9020234] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Revised: 02/01/2022] [Accepted: 02/05/2022] [Indexed: 12/16/2022]
Abstract
In the JPLT3 study, a real-time central surgical reviewing (CSR) system was employed aimed at facilitating early referral of candidates for liver transplantation (LTx) to centers with pediatric LTx services. The expected consequence was surgery, including LTx, conducted at the appropriate time in all cases. This study aimed to review the effect of CSR on institutional surgical decisions in cases enrolled in the JPLT3 study. Real-time CSR was performed in cases in which complex surgeries were expected, using images obtained after two courses of preoperative chemotherapy. Using the cloud-based remote image viewing system, an expert panel consisting of pediatric and transplant surgeons reviewed the images and commented on the expected surgical strategy or the necessity of transferring the patient to a transplant unit. The results were summarized and reported to the treating institutions. A total of 41 reviews were conducted for 35 patients, and 16 cases were evaluated as possible candidates for LTx, with the treating institutions being advised to consult a transplant center. Most of the reviewed cases promptly underwent definitive liver surgeries, including LTx per protocol.
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Affiliation(s)
- Tomoro Hishiki
- Department of Pediatric Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Chiba, Japan;
- Correspondence:
| | - Shohei Honda
- Department of Gastroenterological Surgery I, Hokkaido University Hospital, Sapporo 060-8648, Hokkaido, Japan;
| | - Yuichi Takama
- Department of Pediatric Surgery, Osaka City General Hospital, Osaka 534-0021, Osaka, Japan;
| | | | - Hideaki Okajima
- Department of Pediatric Surgery, Kanazawa Medical University, Kanazawa 920-0293, Ishikawa, Japan;
| | - Ken Hoshino
- Department of Pediatric Surgery, Keio School of Medicine, Keio University, Tokyo 108-8345, Tokyo, Japan;
| | - Tatsuya Suzuki
- Department of Pediatric Surgery, Fujita Health University Hospital, Toyoake 470-1192, Aichi, Japan;
| | - Ryota Souzaki
- Department of Pediatric Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Fukuoka, Japan;
| | - Motoshi Wada
- Department of Pediatric Surgery, Tohoku University School of Medicine, Sendai 980-8574, Miyagi, Japan; (M.W.); (T.K.)
| | - Mureo Kasahara
- Organ Transplantation Center, National Center for Child Health and Development, Tokyo 157-8535, Tokyo, Japan;
| | - Koichi Mizuta
- Transplant Center, Saitama Children’s Medical Center, Saitama 330-8777, Saitama, Japan;
| | - Takaharu Oue
- Department of Pediatric Surgery, Hyogo College of Medicine, Nishinomiya 663-8501, Hyogo, Japan;
| | - Akiko Yokoi
- Department of Pediatric Surgery, Kobe Children’s Hospital, Kobe 650-0047, Hyogo, Japan;
| | - Takuro Kazama
- Department of Pediatric Surgery, Tohoku University School of Medicine, Sendai 980-8574, Miyagi, Japan; (M.W.); (T.K.)
| | - Shugo Komatsu
- Department of Pediatric Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Chiba, Japan;
| | - Isamu Saeki
- Department of Pediatric Surgery, Hiroshima University Hospital, Hiroshima 734-8551, Hiroshima, Japan; (I.S.); (E.H.)
| | - Osamu Miyazaki
- Department of Diagnostic Radiology, National Center for Child Health and Development, Tokyo 157-8535, Tokyo, Japan;
| | - Tetsuya Takimoto
- Department of Childhood Cancer Data Management, National Center for Child Health and Development, Tokyo 157-8535, Tokyo, Japan;
| | - Kohmei Ida
- Department of Pediatrics, Teikyo University Mizonokuchi Hospital, Kawasaki 213-8507, Kanagawa, Japan;
| | - Kenichiro Watanabe
- Department of Hematology and Oncology, Shizuoka Children’s Hospital, Shizuoka 420-8660, Shizuoka, Japan;
| | - Eiso Hiyama
- Department of Pediatric Surgery, Hiroshima University Hospital, Hiroshima 734-8551, Hiroshima, Japan; (I.S.); (E.H.)
- Natural Science Center for Basic Research and Development, Hiroshima University, Hiroshima 734-8551, Hiroshima, Japan
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12
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Leoni J, Rougemont AL, Calinescu AM, Ansari M, Compagnon P, Wilde JCH, Wildhaber BE. Effect of Centralization on Surgical Outcome of Children Operated for Liver Tumors in Switzerland: A Retrospective Comparative Study. CHILDREN 2022; 9:children9020217. [PMID: 35204937 PMCID: PMC8870146 DOI: 10.3390/children9020217] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/26/2021] [Revised: 01/18/2022] [Accepted: 02/01/2022] [Indexed: 11/27/2022]
Abstract
Background: Pediatric liver surgery is complex, and complications are not uncommon. Centralization of highly specialized surgery has been shown to improve quality of care. In 2012, pediatric liver surgery was centralized in Switzerland in one national center. This study analyses results before and after centralization. Methods: Retrospective monocentric comparative study. Analysis of medical records of children (0–16 years) operated for any liver tumor between 1 January 2001 and 31 December 2020. Forty-one patients were included: 14 before centralization (before 1 January 2012) and 27 after centralization (after 1 January 2012). Epidemiological, pre-, intra-, and post-operative data were collected. Fischer’s exact and t-test were used to compare groups. Results: The two cohorts were homogeneous. Operating time was reduced, although not significantly, from 366 to 277 min. Length of postoperative stay and mortality were not statistically different between groups. Yet, after centralization, overall postoperative complication rate decreased significantly from 57% to 15% (p = 0.01), Clavien > III complications decreased from 50% to 7% (p < 0.01), and hepatic recurrences were also significantly reduced (40% to 5%, p = 0.03). Conclusion: Centralization of the surgical management of liver tumors in Switzerland has improved quality of care in our center by significantly reducing postoperative complications and hepatic recurrence.
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Affiliation(s)
- Jasmine Leoni
- Swiss Pediatric Liver Center, Geneva University Hospitals, 1205 Geneva, Switzerland; (J.L.); (A.-L.R.); (A.M.C.); (M.A.); (P.C.); (J.C.H.W.)
- Division of Child and Adolescent Surgery, Department of Women, Child and Adolescent, Geneva University Hospitals, 1205 Geneva, Switzerland
- Department of Pediatrics, Gynecology and Obstetrics, University of Geneva, 1205 Geneva, Switzerland
| | - Anne-Laure Rougemont
- Swiss Pediatric Liver Center, Geneva University Hospitals, 1205 Geneva, Switzerland; (J.L.); (A.-L.R.); (A.M.C.); (M.A.); (P.C.); (J.C.H.W.)
- Diagnostic Department, Division of Clinical Pathology, Swiss Pediatric Liver Center, Geneva University Hospitals, 1205 Geneva, Switzerland
| | - Ana M. Calinescu
- Swiss Pediatric Liver Center, Geneva University Hospitals, 1205 Geneva, Switzerland; (J.L.); (A.-L.R.); (A.M.C.); (M.A.); (P.C.); (J.C.H.W.)
- Division of Child and Adolescent Surgery, Department of Women, Child and Adolescent, Geneva University Hospitals, 1205 Geneva, Switzerland
- Department of Pediatrics, Gynecology and Obstetrics, University of Geneva, 1205 Geneva, Switzerland
| | - Marc Ansari
- Swiss Pediatric Liver Center, Geneva University Hospitals, 1205 Geneva, Switzerland; (J.L.); (A.-L.R.); (A.M.C.); (M.A.); (P.C.); (J.C.H.W.)
- Department of Pediatrics, Gynecology and Obstetrics, University of Geneva, 1205 Geneva, Switzerland
- Unit of Oncology and Haematology, Department of Women, Child and Adolescent, Geneva University Hospitals and CANSEARCH Research Platform in Pediatric Oncology and Hematology, 1205 Geneva, Switzerland
| | - Philippe Compagnon
- Swiss Pediatric Liver Center, Geneva University Hospitals, 1205 Geneva, Switzerland; (J.L.); (A.-L.R.); (A.M.C.); (M.A.); (P.C.); (J.C.H.W.)
- Department of Surgery, Division of Transplantation, University Hospitals of Geneva, 1205 Geneva, Switzerland
| | - Jim C. H. Wilde
- Swiss Pediatric Liver Center, Geneva University Hospitals, 1205 Geneva, Switzerland; (J.L.); (A.-L.R.); (A.M.C.); (M.A.); (P.C.); (J.C.H.W.)
- Division of Child and Adolescent Surgery, Department of Women, Child and Adolescent, Geneva University Hospitals, 1205 Geneva, Switzerland
- Department of Pediatrics, Gynecology and Obstetrics, University of Geneva, 1205 Geneva, Switzerland
| | - Barbara E. Wildhaber
- Swiss Pediatric Liver Center, Geneva University Hospitals, 1205 Geneva, Switzerland; (J.L.); (A.-L.R.); (A.M.C.); (M.A.); (P.C.); (J.C.H.W.)
- Division of Child and Adolescent Surgery, Department of Women, Child and Adolescent, Geneva University Hospitals, 1205 Geneva, Switzerland
- Department of Pediatrics, Gynecology and Obstetrics, University of Geneva, 1205 Geneva, Switzerland
- Correspondence:
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13
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FALQUETO LORAINEENTRINGER, VILAR PAULARUBIO, CAMPOS HELDERGROENWOLD, SCHULZ CLAUDIO, MATTOS E SILVA ELISANGELADE. Neoplasias Malignas Primárias do Fígado: experiência de oito anos de um Hospital Pediátrico no Brasil. Estudo transversal. Rev Col Bras Cir 2022. [DOI: 10.1590/0100-6991e-20223273] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
RESUMO Introdução: tumores hepáticos são neoplasias raras na infância (1-2%), sendo que cerca de 2/3 são malignos. O hepatoblastoma (HB) é o mais frequente, seguido do carcinoma hepatocelular (CHC). Em ambos, o principal tratamento é a ressecção cirúrgica completa. Atualmente, a quimioterapia e o transplante hepático têm melhorado os resultados. Objetivo: estudo do perfil epidemiológico e evolução dos casos de cânceres hepáticos em um hospital pediátrico de referência. Método: Levantamento retrospectivo de prontuários de pacientes até 18 anos com diagnóstico de neoplasia maligna primária hepática entre 2012 e 2020 realizado no maior hospital exclusivamente pediátrico do Brasil. Resultados: foram atendidos 13 pacientes com tumores malignos hepáticos (HB 12, CHC 1). Dos casos de HB, 66,7% eram do sexo masculino, com idade média de 2 anos e a principal alteração foi massa abdominal palpável. Os tumores envolviam em média 3 segmentos hepáticos, mais em lobo direito (54%). Um paciente foi tratado com cirurgia sem neoadjuvância, um foi submetido a transplante inicialmente e outros 2 necessitaram de transplante hepático como resgate. O tempo de seguimento dos pacientes com HB foi de 39 meses e apenas 1 caso foi a óbito por neutropenia febril. A sobrevida geral e livre de doença em 5 anos foi de 91,7% e 81,5% respectivamente. Conclusão: o estadiamento avançado no momento do diagnóstico sempre foi um fator de mau prognóstico em pacientes com tumores hepáticos malignos primários. Entretanto, os resultados e a sobrevida têm melhorado significativamente com o avanço da quimioterapia, da técnica cirúrgica e do transplante hepático.
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Sintusek P, Phewplung T, Sanpavat A, Poovorawan Y. Liver tumors in children with chronic liver diseases. World J Gastrointest Oncol 2021; 13:1680-1695. [PMID: 34853643 PMCID: PMC8603454 DOI: 10.4251/wjgo.v13.i11.1680] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 04/27/2021] [Accepted: 08/23/2021] [Indexed: 02/06/2023] Open
Abstract
Liver tumors are rare in children, but the incidence may increase in some circumstances and particularly in chronic liver diseases. Most liver tumors consequent to chronic liver diseases are malignant hepatocellular carcinoma. Other liver tumors include hepatoblastoma, focal nodular hyperplasia, adenoma, pseudotumor, and nodular regenerative hyperplasia. Screening of suspected cases is beneficial. Imaging and surrogate markers of alpha-fetoprotein are used initially as noninvasive tools for surveillance. However, liver biopsy for histopathology evaluation might be necessary for patients with inconclusive findings. Once the malignant liver tumor is detected in children with cirrhosis, liver transplantation is currently considered the preferred option and achieves favorable outcomes. Based on the current evidence, this review focuses on liver tumors with underlying chronic liver disease, their epidemiology, pathogenesis, early recognition, and effective management.
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Affiliation(s)
- Palittiya Sintusek
- Thai Pediatric Gastroenterology, Hepatology and Immunology Research Unit, Department of Pediatrics, Division of Gastroenterology, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok 10330, Thailand
| | - Teerasak Phewplung
- Department of Radiology, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Bangkok 10330, Thailand
| | - Anapat Sanpavat
- Department of Pathology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
| | - Yong Poovorawan
- Center of Excellence in Clinical Virology, Chulalongkorn University, Bangkok 10330, Thailand
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15
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Feng SG, Bhandari R, Ya L, Zhixuan B, Qiuhui P, Jiabei Z, Sewi M, Ni Z, Jing W, Fenyong S, Ji M, Bhandari R. SNHG9 promotes Hepatoblastoma Tumorigenesis via miR-23a-5p/Wnt3a Axis. J Cancer 2021; 12:6031-6049. [PMID: 34539877 PMCID: PMC8425203 DOI: 10.7150/jca.60748] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Accepted: 07/29/2021] [Indexed: 12/18/2022] Open
Abstract
Background: Hepatoblastoma is a common hepatic tumor occurring in children between 0-5 years. Accumulating studies have shown lncRNA's potential role in distinct cancer progression and development, including hepatoblastoma. SnoRNA host gene 9 (SNHG9) is associated with the progression of distinct human cancers, but, its specific molecular mechanisms in hepatoblastoma is not unknown. Methods: In this study, we estimated SNHG9 expression in hepatoblastoma tissue and cell lines by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). Next, we downregulated and upregulated SNHG9 expression in hepatoblastoma cell lines and then determined cell proliferation (CCK-8), colony formation, and cellular apoptosis activity. The dual luciferase reporter activity, RNA immunoprecipitation (RIP), biotin RNA pull down and Spemann's Pearson correlation coefficient assay were performed to establish the interaction between SNHG9, WNt3a and miR- 23a-5p. A xenograft in-vivo tumorgenicity test was performed to elucidate the role of SNHG9 hepatoblastoma in tumorigenesis. SNHG9 role in Cisplatin drug resistance in hepatoblastoma was also determined. Results: SNHG9 was significantly upregulated in hepatoblastoma tissue and cell lines. SNHG9 overexpression on HUH6 & HepG2 resulted in a significant increase in cell proliferation and clonogenic activity while SNHG9 knock down resulted in a sustained inhibition of cell proliferation and clonogenic activity. Dual luciferase activity, RNA immunoprecipitation and biotin pull down confirmed the direct interaction of miR-23a-5p with SNHG9. The xenograft tumorgenicity test showed SNHG9 downregulation significantly inhibited the tumor growth in BALB/c mice. ROC and Kaplan-Meier analysis showed potential prognostic and diagnostic importance of SNHG9 in hepatoblastoma. Conclusion: We concluded that SNHG9/miR-23a-5p/Wnt3a axis promotes the progression hepatoblastoma tumor.
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Affiliation(s)
- Sun Gui Feng
- Department of Clinical Laboratory Medicine, Chengdu Second Peoples Hospital, Chengdu, Sichuan 610021, PR China.,Department of Clinical Laboratory Medicine, Shanghai Tenth People's Hospital, Tongji University of Medicine Shanghai, China
| | - Rajeev Bhandari
- Department of Clinical Laboratory Medicine, Chengdu Second Peoples Hospital, Chengdu, Sichuan 610021, PR China
| | - Liu Ya
- Department of Clinical Laboratory Medicine, Shanghai Tenth People's Hospital, Tongji University of Medicine Shanghai, China
| | - Bian Zhixuan
- Department of Clinical Laboratory Medicine, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China
| | - Pan Qiuhui
- Department of Clinical Laboratory Medicine, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China
| | - Zhu Jiabei
- Department of Clinical Laboratory Medicine, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China
| | - Mao Sewi
- Department of Clinical Laboratory Medicine, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China
| | - Zhen Ni
- Department of Clinical Laboratory Medicine, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China
| | - Wang Jing
- Department of Clinical Laboratory Medicine, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China
| | - Sun Fenyong
- Department of Clinical Laboratory Medicine, Shanghai Tenth People's Hospital, Tongji University of Medicine Shanghai, China
| | - Ma Ji
- Department of Clinical Laboratory Medicine, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China
| | - Ramesh Bhandari
- Department of Clinical Laboratory Medicine, Shanghai Tenth People's Hospital, Tongji University of Medicine Shanghai, China
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16
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Yağcı-Küpeli B, Ballı T. Hepatoblastoma treated successfully with drug-eluting bead transarterial chemoembolization: Outcome of seven-year follow-up. Pediatr Blood Cancer 2021; 68:e29063. [PMID: 33871930 DOI: 10.1002/pbc.29063] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2021] [Revised: 03/09/2021] [Accepted: 04/01/2021] [Indexed: 11/09/2022]
Affiliation(s)
- Begül Yağcı-Küpeli
- Adana City Education and Research Hospital, Department of Pediatric Hematology/Oncology, University of Health Sciences, Adana, Turkey
| | - Tuğsan Ballı
- Faculty of Medicine, Çukurova University, Deapartment of Radiology, Adana, Turkey
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17
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Fuchs J, Hoffmann K, Murtha-Lemekhova A, Kessler M, Günther P, Frongia G, Probst P, Mehrabi A. Establishing a Standardized Measure of Quality in Pediatric Liver Surgery: Definition and Validation of Textbook Outcome With Associated Predictors. Front Surg 2021; 8:708351. [PMID: 34368218 PMCID: PMC8333609 DOI: 10.3389/fsurg.2021.708351] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Accepted: 06/25/2021] [Indexed: 01/10/2023] Open
Abstract
Purpose: To establish comparable reporting of surgical results in pediatric liver surgery, the recently introduced composite outcome measures Textbook Outcome (TO) and Comprehensive Complication Index (CCI) are applied and validated in a pediatric surgery context for the first time. In a representative cohort of pediatric patients undergoing liver resection, predictive factors for TO and CCI are investigated, and outcomes are compared to available literature on surgical outcomes of pediatric liver resection. Methods: All liver resections for patients under 21 years of age performed at the Department of General, Visceral, Transplantation and Pediatric Surgery of the University of Heidelberg between 2009 and 2020 were included in the analysis. Criteria for TO were defined prior to the analysis. Univariate and Multivariate regression was applied to identify factors associated with TO and CCI. Results: Fifty-three pediatric patients underwent liver resections during the observation period. No 30- or 90-day mortality occurred. Twenty-three patients (43.4%) had a TO. CCI and TO showed highly significant correlation (b = −30.33, 95% CI [−37.44; −23.22], p < 0.001). Multivariate analyses revealed significant association between intraoperative blood loss (adjusted for circulating blood volume) and CCI (b = 0.70, 95%CI [0.22; 1.32], p = 0.008) and failure to achieve TO (OR = 0.85, 95%CI [0.69; 0.97], p = 0.048). Conclusion: TO and CCI are suited outcome measures in pediatric surgical studies and offer objective comparability of results. Their application in clinical studies will be a major step forward to establish evidence-based therapies in pediatric surgery. Systematic utilization of TO and CCI can aid in generating comparable studies on surgical techniques and outcomes in pediatric liver resection.
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Affiliation(s)
- Juri Fuchs
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Katrin Hoffmann
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Anastasia Murtha-Lemekhova
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Markus Kessler
- Division of Pediatric Surgery, Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Patrick Günther
- Division of Pediatric Surgery, Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Giovanni Frongia
- Department of General, Visceral, Thorax, Pediatric and Endocrine Surgery, Johannes Wesling Hospital Minden, Heidelberg, Germany
| | - Pascal Probst
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Arianeb Mehrabi
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
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Abstract
BACKGROUND Pediatric liver tumors are relatively rare, but thorough knowledge of their imaging features is still important. OBJECTIVES Frequency and imaging features of benign and malignant liver masses during childhood and adolescence. MATERIALS AND METHODS Discussion of relevant original articles, review manuscripts and expert recommendations concerning imaging of childhood liver tumors. RESULTS The most common malignant tumors of the liver are hepatoblastoma, which usually occur in younger children, as well as in some regions hepatocellular carcinoma. In contrast to most benign masses, such as focal nodular hyperplasia, simple cysts or fatty liver infiltrations, their imaging morphology is not very characteristic. Radiologically, sonography and magnetic resonance imaging (MRI) are used for assessment. Both methods benefit from intravenous contrast agent administration. CONCLUSIONS Childhood liver tumors show a broad spectrum of morphological manifestations. Some entities can be characterized using standard imaging, some require multimodal imaging or histological assessment. In addition to morphological imaging criteria, age and the medical history as well as laboratory data play an important role in establishing the correct diagnosis.
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Bannoura S, Putra J. Primary malignant vascular tumors of the liver in children: Angiosarcoma and epithelioid hemangioendothelioma. World J Gastrointest Oncol 2021; 13:223-230. [PMID: 33889274 PMCID: PMC8040065 DOI: 10.4251/wjgo.v13.i4.223] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2021] [Revised: 01/26/2021] [Accepted: 03/22/2021] [Indexed: 02/06/2023] Open
Abstract
Primary malignant vascular neoplasms of the liver, angiosarcoma and epithelioid hemangioendothelioma, are extremely rare entities in the pediatric population. International Society for the Study of Vascular Anomalies classification system is recommended for the pathologic diagnosis of hepatic vascular lesions in this age group. In this article, we highlight the clinicopathologic characteristics of hepatic angiosarcoma and epithelioid hemangioendothelioma in the pediatric population. Hepatic angiosarcoma in children shows a slight female predominance with an average age of 40 mo at diagnosis. The distinct histologic features include whorls of atypical spindled cells and eosinophilic globules, in addition to the general findings of angiosarcoma. Histologic diagnosis of pediatric hepatic angiosarcoma is not always straightforward, and the diagnostic challenges are discussed in the article. Hepatic epithelioid hemangioendothelioma also demonstrates a female predominance, but is more commonly identified in adolescents (median age at diagnosis: 12 years). Histologically, the lesion is characterized by epithelioid cells and occasional intracytoplasmic lumina with a background of fibromyxoid stroma. While WWTR1-CAMTA1 and YAP1-TFE3 fusions have been associated with epithelioid hemangioendothelioma, there are currently no known signature genetic alterations seen in pediatric hepatic angiosarcoma. Advancement in molecular pathology, particularly for pediatric hepatic angiosarcoma, is necessary for a better understanding of the disease biology, diagnosis, and development of targeted therapies.
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Affiliation(s)
- Sami Bannoura
- Department of Paediatric Laboratory Medicine, Hospital for Sick Children, 555 University Ave, Toronto M5G 1X8, Ontario, Canada
| | - Juan Putra
- Department of Paediatric Laboratory Medicine, Hospital for Sick Children, 555 University Ave, Toronto M5G 1X8, Ontario, Canada
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20
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Wang G, Xie X, Chen H, Zhong Z, Zhou W, Jiang H, Xie X, Zhou L. Development of a pediatric liver CEUS criterion to classify benign and malignant liver lesions in pediatric patients: a pilot study. Eur Radiol 2021; 31:6747-6757. [PMID: 33666698 DOI: 10.1007/s00330-021-07784-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2020] [Revised: 12/09/2020] [Accepted: 02/12/2021] [Indexed: 12/15/2022]
Abstract
OBJECTIVES To analyze the contrast-enhanced ultrasound (CEUS) characteristics of pediatric patients with focal liver lesions (FLLs) and develop a pediatric liver CEUS criterion to improve the diagnostic performance of CEUS in differentiating pediatric benign and malignant liver lesions. METHODS Between March 2011 and May 2020, patients < 18 years who underwent CEUS were retrospectively evaluated. The CEUS characteristics of FLLs were analyzed. A pediatric liver CEUS criterion categorized as CEUS-1 to CEUS-5 was developed. The diagnostic performance of the criterion (i.e., sensitivity, specificity, PPV, and NPV) was assessed. Chi-square and Mann-Whitney tests were used. RESULTS After exclusion, the study included 130 lesions (mean diameter, 7.1 cm; range, 0.8-17.0 cm) from 130 patients (mean age, 36.0 months; range, 0.03-204.0 months; 74 boys). Hyperenhancement with washout in patients < 5 years or with early washout (≤ 45 s) was used to predict hepatoblastoma, with a sensitivity and specificity of 90.7% (95% confidence interval [CI]: 77.9%, 97.4%) and 93.6% (95% CI: 84.3%, 98.2%), respectively. Peripheral discontinuous globular hyperenhancement was used to diagnose hemangioma, with a sensitivity and specificity of 84.6% (95% CI: 65.1%, 95.6%) and 100% (95% CI: 95.4%, 100.0%), respectively. The rates of malignancies within the pediatric liver CEUS-1, CEUS-2, CEUS-3, CEUS-4, and CEUS-5 categories were 0.0%, 0.0%, 5.6%, 50.0%, and 96.1%, respectively. Besides, the incidences of hepatoblastoma in pediatric liver CEUS-3, CEUS-4, and CEUS-5 were 5.6%, 16.7%, and 67.5%, respectively. CONCLUSIONS The pediatric liver CEUS criterion is useful in differentiating benign focal liver lesions from malignancies, especially hepatoblastoma from hemangioma. KEY POINTS • Hyperenhancement with washout in patients <v5 years or with early washout (≤ 45 s) were used to predict hepatoblastoma, with a sensitivity and specificity of 90.7% and 93.6%. • Peripheral discontinuous globular hyperenhancement was used to diagnose hemangioma, with a sensitivity and specificity of 84.6% and 100.0%. • The rates of malignancies within the pediatric liver CEUS-1, CEUS -2, CEUS-3, CEUS-4, and CEUS-5 categories were 0.0%, 0.0%, 5.6%, 50.0%, and 96.1%, respectively.
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Affiliation(s)
- Guotao Wang
- Department of Medical Ultrasonics, Institute for Diagnostic and Interventional Ultrasound, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan Er Road, Guangzhou, 510080, People's Republic of China
| | - Xiaohua Xie
- Department of Medical Ultrasonics, Institute for Diagnostic and Interventional Ultrasound, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan Er Road, Guangzhou, 510080, People's Republic of China
| | - Huadong Chen
- Department of Pediatric Surgery, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan Er Road, Guangzhou, 510080, People's Republic of China
| | - Zhihai Zhong
- Department of Pediatric Surgery, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan Er Road, Guangzhou, 510080, People's Republic of China
| | - Wenying Zhou
- Department of Medical Ultrasonics, Institute for Diagnostic and Interventional Ultrasound, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan Er Road, Guangzhou, 510080, People's Republic of China
| | - Hong Jiang
- Department of Pediatric Surgery, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan Er Road, Guangzhou, 510080, People's Republic of China
| | - Xiaoyan Xie
- Department of Medical Ultrasonics, Institute for Diagnostic and Interventional Ultrasound, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan Er Road, Guangzhou, 510080, People's Republic of China
| | - Luyao Zhou
- Department of Medical Ultrasonics, Institute for Diagnostic and Interventional Ultrasound, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan Er Road, Guangzhou, 510080, People's Republic of China.
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21
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AlFawaz I, Ahmed B, Ali A, Ayas M, AlKofide A, Habib Z, Siddiqui K. Experience of treating pediatric hepatoblastoma at King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia - Timely surgical intervention playing a key role. Int J Pediatr Adolesc Med 2021; 8:39-43. [PMID: 33718576 PMCID: PMC7922831 DOI: 10.1016/j.ijpam.2020.11.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2020] [Revised: 09/10/2020] [Accepted: 11/05/2020] [Indexed: 12/04/2022]
Abstract
BACKGROUND Many studies have demonstrated that outcome in patients with hepatoblastoma is determined by tumor resectability and the presence or absence of metastatic disease. PURPOSE To evaluate and disseminate information on diagnosis, treatment, and outcome of hepatoblastoma patients at a tertiary care hospital in Saudi Arabia. PATIENTS AND METHODS Twenty-four pediatric patients with hepatoblastoma were treated at our institution between January 2005 and December 2012. The majority of our patients were stage III and above, while one-third of them presented with metastatic disease. Four (16.7%) had vascular invasion. Two-thirds of our patients (n = 16, 66.7%) had alpha-fetoprotein (AFP) level above 100,000 ng/mL. Twenty-one patients underwent surgery; two had upfront surgery before getting any chemotherapy, and 15 had surgery on schedule after pre-operative chemotherapy. Four patients had delayed surgery as the tumor was not resectable and received extra cycles of chemotherapy. Chemotherapy regimens used were based on SIOPEL study protocols until 2011 and Children's Oncology Group (COG) protocol from 2012 onwards. Relapse, progressive disease, or death from any cause were defined as events. RESULTS Five-year overall survival (OS) of the cohort over a median follow-up time of 56.1 months was 70.6% ± 9.4% with seven (29.2%) events of mortality. No significant difference was found for age at diagnosis (less than 2 years vs. more), stage of disease, AFP levels (less than 100,000 vs. more), vascular invasion, or presence of metastatic disease at presentation in terms of OS. However, children receiving upfront or scheduled as-per-protocol surgery fared better than those who had delayed surgery (as the tumor was not resectable and they received extra cycles of chemotherapy) or did not undergo any surgery (P-Value .001). CONCLUSION Favorable survival outcome could be achieved with complete tumor excision and adjuvant chemotherapy. Inability to perform surgical excision was the single most important predictor of mortality in our patients.
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Affiliation(s)
- Ibrahim AlFawaz
- Department of Pediatric Hematology/Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - Basheer Ahmed
- Department of Pediatric Hematology/Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - Afshan Ali
- Department of Pediatric Hematology/Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - Mouhab Ayas
- Department of Pediatric Hematology/Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - Amani AlKofide
- Department of Pediatric Hematology/Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - Zakaria Habib
- Department of Surgery King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - Khawar Siddiqui
- Department of Pediatric Hematology/Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
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22
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Karalexi MA, Servitzoglou M, Moschovi M, Moiseenko R, Bouka P, Ntzani E, Kachanov D, Petridou ET. Survival and prognostic factors for childhood malignant liver tumors: analysis of harmonized clinical data. Cancer Epidemiol 2021; 70:101850. [PMID: 33220637 DOI: 10.1016/j.canep.2020.101850] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2020] [Revised: 10/16/2020] [Accepted: 10/18/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Despite overall striking advances in survival of childhood liver tumors, outcomes remain poor for specific patient segments. We aimed to assess overall survival (OS) of this rare disease and evaluate the generalizability of prognostic variables included in international collaborative systems using, for the first time, harmonized clinical data from two geographically different cohorts (Greece and Moscow). METHODS Data for children (0-14 years) with liver tumors were retrieved from two Southern-Eastern European areas (Greece; 2001-2019 and Moscow; 2012-2019). Kaplan-Meier curves were constructed, and OS values were derived from Cox proportional models controlling for study variables. RESULTS A total of 171 newly diagnosed cases (54.4% males) were included. The OS5-year exceeded 80% in patients <5 years, reaching 85% among 133 patients with hepatoblastoma (HBL). By contrast, children with other than HBL histology, especially hepatocellular carcinoma (HCC) had significantly worse prognosis (hazard ratio [HR] HCC: 7.09, 95% confidence intervals [CI]: 2.56-19.65; HR other liver tumors: 5.18; 95%CI: 2.15-12.49). The OS5-year was poorer (40%-60%) in patients with extensive local, metastatic or relapsed disease. By contrast, a significantly lower risk of death was shown in case of microscopically margin-negative resection (HR: 0.06, 95%CI: 0.02-0.17) and liver transplantation (HR: 0.12, 95% CI: 0.02-0.63) compared to the non- operated group. CONCLUSIONS Outcomes of patients with liver tumors registered in two SEE areas were comparable to those reported by major collaborative trials. Ongoing clinical cancer registration could facilitate comparison of outcomes between different study groups in order to shape state of the art of treatment.
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Affiliation(s)
- Maria A Karalexi
- Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Marina Servitzoglou
- Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Maria Moschovi
- Pediatric Hematology/Oncology Unit, First Department of Pediatrics, National and Kapodistrian University of Athens, "Agia Sofia" Children's Hospital, Athens, Greece
| | - Roman Moiseenko
- Department of Clinical Oncology, Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia
| | - Panagiota Bouka
- Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Evangelia Ntzani
- Department of Hygiene and Epidemiology, School of Medicine, University of Ioannina, Greece; Center for Evidence Synthesis in Health, Brown University School of Public Health, Providence, RI, USA
| | - Denis Kachanov
- Department of Clinical Oncology, Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia
| | - Eleni Th Petridou
- Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, Athens, Greece; Clinical Epidemiology Unit, Department of Medicine, Karolinska Institute, Stockholm, Sweden.
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23
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Sudden and unexpected death in childhood due to an undiagnosed hepatoblastoma: Case report and review of literature. J Forensic Leg Med 2020; 77:102086. [PMID: 33242744 DOI: 10.1016/j.jflm.2020.102086] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Accepted: 11/14/2020] [Indexed: 11/20/2022]
Abstract
The sudden and unexpected death of an infant or child due to cancer is a particularly rare event. Most of the cases concern primary growths located in vital organs such as the heart or the brain. Only in an extremely small number of cases does it occur in infants or children affected by liver cancer. Herein we report the sudden and unexpected death of a 3-and-a-half-year-old infant, who due to an undiagnosed tumor of the liver, namely hepatoblastoma, suffered a major intra-abdominal (hemoperitoneum) bleed, leading to a fatal hemorrhagic trauma. In cases like these, it is of utmost importance to carry out both an autopsy as well as complete histological tests in order to determine if the hepatic tumor is the real cause of death or if it was a mere chance finding. In the case of sudden and unexplained deaths in infancy and childhood, the forensic pathologist should always consider that other complications, for example, those correlated with hepatoblastoma could, in fact, cause sudden death given that this particular tumor is often scarcely symptomatic and can remain undiscovered for a long period of time.
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24
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Eloranta K, Cairo S, Liljeström E, Soini T, Kyrönlahti A, Judde JG, Wilson DB, Heikinheimo M, Pihlajoki M. Chloroquine Triggers Cell Death and Inhibits PARPs in Cell Models of Aggressive Hepatoblastoma. Front Oncol 2020; 10:1138. [PMID: 32766148 PMCID: PMC7379510 DOI: 10.3389/fonc.2020.01138] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Accepted: 06/05/2020] [Indexed: 12/28/2022] Open
Abstract
Background: Hepatoblastoma (HB) is the most common pediatric liver malignancy. Despite advances in chemotherapeutic regimens and surgical techniques, the survival of patients with advanced HB remains poor, underscoring the need for new therapeutic approaches. Chloroquine (CQ), a drug used to treat malaria and rheumatologic diseases, has been shown to inhibit the growth and survival of various cancer types. We examined the antineoplastic activity of CQ in cell models of aggressive HB. Methods: Seven human HB cell models, all derived from chemoresistant tumors, were cultured as spheroids in the presence of relevant concentrations of CQ. Morphology, viability, and induction of apoptosis were assessed after 48 and 96 h of CQ treatment. Metabolomic analysis and RT-qPCR based Death Pathway Finder array were used to elucidate the molecular mechanisms underlying the CQ effect in a 2-dimensional cell culture format. Quantitative western blotting was performed to validate findings at the protein level. Results: CQ had a significant dose and time dependent effect on HB cell viability both in spheroids and in 2-dimensional cell cultures. Following CQ treatment HB spheroids exhibited increased caspase 3/7 activity indicating the induction of apoptotic cell death. Metabolomic profiling demonstrated significant decreases in the concentrations of NAD+ and aspartate in CQ treated cells. In further investigations, oxidation of NAD+ decreased as consequence of CQ treatment and NAD+/NADH balance shifted toward NADH. Aspartate supplementation rescued cells from CQ induced cell death. Additionally, downregulated expression of PARP1 and PARP2 was observed. Conclusions: CQ treatment inhibits cell survival in cell models of aggressive HB, presumably by perturbing NAD+ levels, impairing aspartate bioavailability, and inhibiting PARP expression. CQ thus holds potential as a new agent in the management of HB.
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Affiliation(s)
- Katja Eloranta
- Pediatric Research Center, Children's Hospital, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
| | | | - Emmi Liljeström
- Pediatric Research Center, Children's Hospital, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
| | - Tea Soini
- Pediatric Research Center, Children's Hospital, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.,Department of Medicine, Center for Infectious Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Antti Kyrönlahti
- Pediatric Research Center, Children's Hospital, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
| | | | - David B Wilson
- Department of Pediatrics, Washington University School of Medicine, St. Louis Children's Hospital, St. Louis, MO, United States.,Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, United States
| | - Markku Heikinheimo
- Pediatric Research Center, Children's Hospital, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.,Department of Pediatrics, Washington University School of Medicine, St. Louis Children's Hospital, St. Louis, MO, United States
| | - Marjut Pihlajoki
- Pediatric Research Center, Children's Hospital, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
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25
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Isolated hepatic lymphangiomas in children: Two case reports. JOURNAL OF PEDIATRIC SURGERY CASE REPORTS 2020. [DOI: 10.1016/j.epsc.2020.101430] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
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26
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Zavras N, Dimopoulou A, Machairas N, Paspala A, Vaos G. Infantile hepatic hemangioma: current state of the art, controversies, and perspectives. Eur J Pediatr 2020; 179:1-8. [PMID: 31758313 DOI: 10.1007/s00431-019-03504-7] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2019] [Revised: 08/11/2019] [Accepted: 10/09/2019] [Indexed: 12/13/2022]
Abstract
Infantile hepatic hemangioma (IHH) is a common vascular tumor, distinctive for its perinatal presentation, rapid growth during the first year of life, and subsequent involution. Although they generally follow a benign course, some tumors have been reported to undergo malignant transformation. The diagnosis of IHH is based on patient's medical history, physical examination, and imaging. Moreover, the management of this vascular tumor is based on clinical presentation and includes observational, medical, surgical, and radiological interventional treatment options. The present review presents the currently available data in the literature on the diverse aspects of the terminology, epidemiology, clinical presentation, pathogenesis, diagnosis, indications for surgery, malignant potential, and long-term outcomes of these tumors.Conclusion: No formal guidelines have yet been established for the treatment of these hepatic lesions, and the therapeutic strategies implemented vary widely from simple observation to medical, radiological, and surgical interventions in the prism of multidisciplinary teams.What is Known:• Infantile hepatic hemangioma is the most common benign tumor of the liver in infancy, but despite its benign nature, it can present with life-threatening complications.• The treatment strategies range from simple observation to a series of medical, surgical, and radiological interventions.What is New:• This review gives an overview of the developments and current status about the management of IHH.• The aim of this study is to clear up the confusion and controversy that exists about terminology, diagnosis, and treatment of IHH.
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Affiliation(s)
- Nikolaos Zavras
- Department of Paediatric Surgery, "ATTIKON" General University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Anastasia Dimopoulou
- Department of Paediatric Surgery, "ATTIKON" General University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
| | - Nikolaos Machairas
- Third Department of Surgery, "ATTIKON" General University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Anna Paspala
- Third Department of Surgery, "ATTIKON" General University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - George Vaos
- Department of Paediatric Surgery, "ATTIKON" General University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
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Feng J, Polychronidis G, Heger U, Frongia G, Mehrabi A, Hoffmann K. Incidence trends and survival prediction of hepatoblastoma in children: a population-based study. Cancer Commun (Lond) 2019; 39:62. [PMID: 31651371 PMCID: PMC6813130 DOI: 10.1186/s40880-019-0411-7] [Citation(s) in RCA: 91] [Impact Index Per Article: 15.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2019] [Accepted: 10/16/2019] [Indexed: 12/21/2022] Open
Abstract
Background Hepatoblastoma is a rare disease that nevertheless accounts for the majority of liver malignancies in children. Due to limited epidemiological data, therapy for hepatoblastoma tends to be individualized. This study aimed to evaluate incidence trends of hepatoblastoma and to develop a nomogram to predict the survival of children with newly diagnosed hepatoblastoma on a population-based level. Methods Individuals up to 18 years of age with hepatoblastoma recorded in 18 registries of the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015 were examined. Joinpoint regression analyses were applied to assess incidence trends in annual percentage change (APC). Multivariable Cox regression was used to identify factors associated with overall survival (OS). A nomogram was constructed to predict OS in individual cases based on independent predictors. Concordance index (C-index) and calibration curves were used to evaluate predictive performance. Results Between 2004 and 2015, hepatoblastoma incidence increased significantly (APC, 2.2%; 95% confidence interval [CI] 0.5% to 3.8%, P < 0.05). In particular, this increase was observed among 2- to 4-year-old patients, males, and African–Americans. The 5- and 10-year OS rates were 81.5% and 81.0%, respectively. Age of 2 to 4 years, African–American ethnicity, and no surgery were independent predictors for short OS. Distant disease at presentation was found not to be an independent factor of survival. The nomogram had a C-index of 0.79 (95% CI 0.74–0.84) with appropriate calibration curve fitting. Conclusions We constructed a nomogram that integrates common factors associated with survival for hepatoblastoma patients. It provides accurate prognostic prediction for children with hepatoblastoma.
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Affiliation(s)
- Jincheng Feng
- Department of General, Visceral and Transplant Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany
| | - Georgios Polychronidis
- Department of General, Visceral and Transplant Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany
| | - Ulrike Heger
- Department of General, Visceral and Transplant Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany
| | - Giovanni Frongia
- Department of Pediatric Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany
| | - Arianeb Mehrabi
- Department of General, Visceral and Transplant Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany
| | - Katrin Hoffmann
- Department of General, Visceral and Transplant Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany.
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Herden U, Grabhorn E, Lenhartz H, Kütemeier R, Fischer L. Excellent Outcome Following Liver Transplantation for Hepatoblastoma Using an Extensive En Bloc Hepatectomy Technique. Transplant Proc 2019; 51:1887-1891. [PMID: 31262438 DOI: 10.1016/j.transproceed.2019.04.025] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2018] [Revised: 04/15/2019] [Accepted: 04/25/2019] [Indexed: 10/26/2022]
Abstract
BACKGROUND Hepatoblastoma is a rare malignancy but the most common primary hepatic malignancy in childhood. Pediatric liver transplantation (LT) offers the possibility to achieve a complete resection in otherwise unresectable tumors. Almost no data are available regarding specific surgical technique of LT in children with hepatoblastoma. METHODS We analyzed all children with hepatoblastoma and LT between 2007 and 2012. Special regard was given to the surgical technique and long-term follow-up. RESULTS Overall 7 children were transplanted with the diagnosis of hepatoblastoma (5 male, 2 female). Thereof, 4 children (median age was 11 months, range, 6-31 months) underwent "primary" LT for hepatoblastoma Pretreatment Extent of Disease III to IV. A 4-year-old boy received "salvage" LT for recurrent hepatoblastoma 2.5 years after successful liver resection. Another 15-year-old boy was transplanted as a prophylactic treatment after repeated liver resection for hepatoblastoma due to the high recurrence risk. A 14-year-old boy underwent LT due to complications following liver resection for hepatoblastoma during infancy. In all children, extensive en bloc hepatectomy was performed together with resection of the adjoining retroperitoneal tissue and regional lymphadenectomy. Actually, all children are alive without tumor recurrence median 7.1 years after LT (range, 5.7-10.7 years). CONCLUSION Our data show an excellent long-term outcome in selected children with hepatoblastoma undergoing standardized en bloc hepatectomy for "primary" and "rescue" LT with 100% overall and recurrence-free survival.
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Affiliation(s)
- Uta Herden
- Department of Visceral Transplant Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
| | - Enke Grabhorn
- Department of Paediatric Hepatology and Liver Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Henning Lenhartz
- Department of Paediatric Hepatology and Liver Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Robert Kütemeier
- Institute of Legal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Lutz Fischer
- Department of Visceral Transplant Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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29
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Wang Y, Jia L, Wang X, Fu L, Liu J, Qian L. Diagnostic Performance of 2-D Shear Wave Elastography for Differentiation of Hepatoblastoma and Hepatic Hemangioma in Children under 3 Years of Age. ULTRASOUND IN MEDICINE & BIOLOGY 2019; 45:1397-1406. [PMID: 30979592 DOI: 10.1016/j.ultrasmedbio.2019.02.007] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/28/2018] [Revised: 02/03/2019] [Accepted: 02/06/2019] [Indexed: 05/25/2023]
Abstract
The aim of the present study was to prospectively evaluate the clinical efficiency of 2-D shear wave elastography (2-D-SWE) for differentiating hepatoblastoma and hepatic hemangioma in children under 3 y of age. 2-D-SWE was performed in 109 consecutive patients with confirmed hepatic neoplasms by pathologic analysis or contrast-enhanced computed tomography plus follow-up observation, in which 71 patients were defined as the test group, and the remaining 38 patients were defined as the validation group. An elasticity value was obtained from each lesion. The diagnostic performance and optimal cut-off value were determined by receiver operating characteristic (ROC) analysis in the test group, and the accuracy of this threshold was analyzed in the validation group. The interclass correlation coefficient (ICC) and Spearman rank correlation tests were applied to assess the reproducibility of elastic measurement and the relationship between the elasticity value and potential influencing parameters. The mean elasticity values were 58.4 ± 19.5 kPa for hepatoblastoma and 19.0 ± 16.0 kPa for hemangioma (Z = -7.685, p = 0.000). The cut-off value in the test group was 39.5 kPa with an area under the ROC curve for differentiation of 0.915, sensitivity of 88.1% and specificity of 86.2%. The accuracy of this threshold in the validation group was 86.8%. The ICCs for inter- and intra-observer reproducibility for acquisition of the elastic measurement were 0.946 and 0.971, respectively. No significant correlation was found between the elasticity value and age for either hemangioma (r = 0.205, p = 0.167) or hepatoblastoma (r = 0.047, p = 0.715). The elasticity value was positively correlated with lesion size (r = 0.332, p = 0.023) in patients with hemangioma but not in patients with hepatoblastoma (r = 0.222, p = 0.082). As a complementary method, 2-D-SWE may aid the differentiation of hepatoblastoma and hemangioma.
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Affiliation(s)
- Yu Wang
- Department of Ultrasound, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
| | - Liqun Jia
- Department of Ultrasound, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China
| | - Xiaoman Wang
- Department of Ultrasound, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China
| | - Libing Fu
- Department of Pathology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China
| | - Jibin Liu
- Department of Radiology, Thomas Jefferson University, Philadelphia, PA, USA
| | - Linxue Qian
- Department of Ultrasound, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
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Weeda VB, Aronson DC, Verheij J, Lamers WH. Is hepatocellular carcinoma the same disease in children and adults? Comparison of histology, molecular background, and treatment in pediatric and adult patients. Pediatr Blood Cancer 2019; 66:e27475. [PMID: 30259629 DOI: 10.1002/pbc.27475] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2018] [Revised: 08/10/2018] [Accepted: 09/05/2018] [Indexed: 12/11/2022]
Abstract
Pediatric hepatocellular carcinoma (HCC) is rare, resulting in scattered knowledge of tumor biology and molecular background. Thus far, the variant in children has been treated as a different entity from adult HCC. We weigh the hypothesis that HCC in the pediatric and adult groups may be the same entity and may benefit from the same treatment. Although certain differences between adult and pediatric HCC are obvious and certain types of HCC may ask for a customized approach, in conventional HCC, similarities predominate, warranting treatment aiming at common molecular targets in adult and pediatric HCC patients.
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Affiliation(s)
- V B Weeda
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
| | - D C Aronson
- Department of Paediatric Surgery, University Children's Hospital Zürich, Zürich, Switzerland
| | - J Verheij
- Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands
| | - W H Lamers
- Tytgat Institute for Liver and Intestinal Research, Amsterdam, The Netherlands
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31
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Abstract
Although liver tumors are rare in the pediatric population, they are common in the setting of children with specific risk factors requiring increased awareness and, in some instances, screening. The evaluation of a liver mass in children is largely driven by the age at diagnosis, the presence of any medical comorbidities, and initial testing with alpha fetoprotein and imaging. Specific guidelines for the management of different tumors have been implemented in recent years such that a multidisciplinary approach is ideal and care should be provided by centers with experience in their management.
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Affiliation(s)
- Kenneth Ng
- Department of Pediatrics, Johns Hopkins School of Medicine, 600 North Wolfe Street, CMSC 2-117, Baltimore, MD 21287, USA
| | - Douglas B Mogul
- Department of Pediatrics, Johns Hopkins School of Medicine, 600 North Wolfe Street, CMSC 2-117, Baltimore, MD 21287, USA.
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32
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Baumann U, Adam R, Duvoux C, Mikolajczyk R, Karam V, D'Antiga L, Chardot C, Coker A, Colledan M, Ericzon BG, Line PD, Hadzic N, Isoniemi H, Klempnauer JL, Reding R, McKiernan PJ, McLin V, Paul A, Salizzoni M, Furtado ESB, Schneeberger S, Karch A. Survival of children after liver transplantation for hepatocellular carcinoma. Liver Transpl 2018; 24:246-255. [PMID: 29222922 DOI: 10.1002/lt.24994] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2017] [Revised: 11/06/2017] [Accepted: 11/06/2017] [Indexed: 12/12/2022]
Abstract
Hepatocellular carcinoma (HCC) in childhood differs from adult HCC because it is often associated with inherited liver disease. It is, however, unclear whether liver transplantation (LT) for HCC in childhood with or without associated inherited disease has a comparable outcome to adult HCC. On the basis of data from the European Liver Transplant Registry (ELTR), we aimed to investigate if there are differences in patient and graft survival after LT for HCC between children and adults and between patients with underlying inherited versus noninherited liver disease, respectively. We included all 175 children who underwent LT for HCC and were enrolled in ELTR between 1985 and 2012. Of these, 38 had an associated inherited liver disease. Adult HCC patients with (n = 79) and without (n = 316, matched by age, sex, and LT date) inherited liver disease served as an adult comparison population. We used multivariable piecewise Cox regression models with shared frailty terms (for LT center) to compare patient and graft survival between the different HCC groups. Survival analyses demonstrated a superior longterm survival of children with inherited liver disease when compared with children with HCC without inherited liver disease (hazard ratio [HR], 0.29; 95% CI, 0.10-0.90; P = 0.03) and adults with HCC with inherited liver disease (HR, 0.27; 95% CI, 0.06-1.25; P = 0.09). There was no survival difference between adults with and without inherited disease (HR, 1.05; 95% CI, 0.66-1.66; P = 0.84). In conclusion, the potential survival advantage of children with an HCC based on inherited disease should be acknowledged when considering transplantation and prioritization for these patients. Further prospective studies accounting for tumor size and extension at LT are necessary to fully interpret our findings. Liver Transplantation 24 246-255 2018 AASLD.
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Affiliation(s)
- Ulrich Baumann
- Department for Pediatric Kidney, Liver, and Metabolic Diseases, Division of Pediatric Gastroenterology and Hepatology, Hannover Medical School, Hannover, Germany
| | - René Adam
- European Liver Transplant Registry, INSERM U 935, AP-HP Hôpital Paul Brousse, Université Paris-Sud, Villejuif, France
| | - Christophe Duvoux
- Department of Hepatology and Liver Transplant Unit, Henri Mondor Hospital AP-HP, Paris Est University, Créteil, France
| | - Rafael Mikolajczyk
- Research Group Epidemiological and Statistical Methods, Helmholtz Centre for Infection Research, Braunschweig, Germany
- German Center for Infection Research, Hannover-Braunschweig Site, Braunschweig, Germany
| | - Vincent Karam
- European Liver Transplant Registry, INSERM U 935, AP-HP Hôpital Paul Brousse, Université Paris-Sud, Villejuif, France
| | - Lorenzo D'Antiga
- Pediatric Hepatology, Gastroenterology and Transplantation, Hospital Papa Giovanni XXIII, Bergamo, Italy
| | - Christophe Chardot
- Hopital Necker Enfants Malades, Service de Chirurgie Pediatrique, Paris, France
| | - Ahmet Coker
- Division of Hepatobiliary and Liver Transplantation, Department of Surgery Division, Ege University Medical School, Izmir, Turkey
| | - Michele Colledan
- Papa Giovanni 23 Hospital, Chirurgia III e Centro Trapianti di Fegato, Bergamo, Italy
| | - Bo-Goran Ericzon
- Department of Transplantation Surgery, Huddinge Hospital, Huddinge, Sweden
| | - Pål Dag Line
- Radiumhospitalet Medical Center Liver Transplant Unit, Rikshospitalet, Oslo, Norway
| | | | - Helena Isoniemi
- Transplantation and Liver Surgery Clinic, U.C.Helsingfors, Helsinki, Finland
| | - Jürgen L Klempnauer
- Klinik für Viszeral und Transplantationschirurgie, Hannover Medical School, Hannover, Germany
| | - Raymond Reding
- Cliniques Universitaires Saint Luc, Catholic University of Louvain, Brussels, Belgium
| | | | - Valérie McLin
- Swiss Center for Liver Disease in Children, Hôpitaux Universitaires de Genève, Genève, Switzerland
| | - Andreas Paul
- Klinik für allgemeine und Transplantationschirurgie, C.U.K. GHS Essen, Essen, Germany
| | - Mauro Salizzoni
- Centro de Trapianti de Fegato, Azienda Ospedaliera S. Giovanni Battista, Torino, Italy
| | - Emanuel San Bento Furtado
- Gabinete de Coordenacao de Colheita de Orgaos e Transplantacao, Hospitais da Universidade de Coimbra, Coimbra, Portugal
| | - Stefan Schneeberger
- Department of General and Transplant Surgery, University Hospital, Innsbruck, Austria
| | - André Karch
- Research Group Epidemiological and Statistical Methods, Helmholtz Centre for Infection Research, Braunschweig, Germany
- German Center for Infection Research, Hannover-Braunschweig Site, Braunschweig, Germany
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Hishiki T, Watanabe K, Ida K, Hoshino K, Iehara T, Aoki Y, Kazama T, Kihira K, Takama Y, Taguchi T, Fujimura J, Honda S, Matsumoto K, Mori M, Yano M, Yokoi A, Tanaka Y, Fuji H, Miyazaki O, Yoshimura K, Takimoto T, Hiyama E. The role of pulmonary metastasectomy for hepatoblastoma in children with metastasis at diagnosis: Results from the JPLT-2 study. J Pediatr Surg 2017; 52:2051-2055. [PMID: 28927977 DOI: 10.1016/j.jpedsurg.2017.08.031] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2017] [Accepted: 08/28/2017] [Indexed: 12/11/2022]
Abstract
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.
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Affiliation(s)
- Tomoro Hishiki
- Japan Children's Cancer Group (JCCG) liver tumor committee (JPLT).
| | | | - Kohmei Ida
- Japan Children's Cancer Group (JCCG) liver tumor committee (JPLT)
| | - Ken Hoshino
- Japan Children's Cancer Group (JCCG) liver tumor committee (JPLT)
| | - Tomoko Iehara
- Japan Children's Cancer Group (JCCG) liver tumor committee (JPLT)
| | - Yuki Aoki
- Japan Children's Cancer Group (JCCG) liver tumor committee (JPLT)
| | - Takuro Kazama
- Japan Children's Cancer Group (JCCG) liver tumor committee (JPLT)
| | - Kentaro Kihira
- Japan Children's Cancer Group (JCCG) liver tumor committee (JPLT)
| | - Yuichi Takama
- Japan Children's Cancer Group (JCCG) liver tumor committee (JPLT)
| | - Tomoaki Taguchi
- Japan Children's Cancer Group (JCCG) liver tumor committee (JPLT)
| | - Junya Fujimura
- Japan Children's Cancer Group (JCCG) liver tumor committee (JPLT)
| | - Shohei Honda
- Japan Children's Cancer Group (JCCG) liver tumor committee (JPLT)
| | | | - Makiko Mori
- Japan Children's Cancer Group (JCCG) liver tumor committee (JPLT)
| | - Michihiro Yano
- Japan Children's Cancer Group (JCCG) liver tumor committee (JPLT)
| | - Akiko Yokoi
- Japan Children's Cancer Group (JCCG) liver tumor committee (JPLT)
| | - Yukichi Tanaka
- Japan Children's Cancer Group (JCCG) liver tumor committee (JPLT)
| | - Hiroshi Fuji
- Japan Children's Cancer Group (JCCG) liver tumor committee (JPLT)
| | - Osamu Miyazaki
- Japan Children's Cancer Group (JCCG) liver tumor committee (JPLT)
| | | | - Tetsuya Takimoto
- Japan Children's Cancer Group (JCCG) liver tumor committee (JPLT)
| | - Eiso Hiyama
- Japan Children's Cancer Group (JCCG) liver tumor committee (JPLT)
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Lee E, Hodgkinson N, Fawaz R, Vakili K, Kim HB. Multivisceral transplantation for abdominal tumors in children: A single center experience and review of the literature. Pediatr Transplant 2017; 21. [PMID: 28393434 DOI: 10.1111/petr.12904] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/19/2017] [Indexed: 12/29/2022]
Abstract
Standard management of intra-abdominal pediatric solid tumors requires complete resection. However, tumors with multiple organ and vascular involvement present a unique surgical challenge. We conducted a retrospective chart review of four patients, aged 2-14 years, undergoing MVT for intra-abdominal tumors with significant involvement of the visceral arteries and/or portomesenteric venous system at our institution. Indications for MVT included hepatocellular carcinoma, inflammatory myofibroblastic tumor, and two cases of hepatoblastoma. Grafts included liver, stomach, small bowel, and pancreas in all patients, with two patients also receiving spleens, and one, a partial esophageal transplant. Median hospital stay was 80 days. Postoperative complications included reoperation for abdominal hematoma and bowel obstruction, steroid responsive intestinal rejection, wound dehiscence, fungemia, seizures, and chyle leak with pleural effusion. One patient developed Epstein-Barr virus-associated complications which responded well to treatment. On follow-up (range 2.8-7.8 years), all patients have satisfactory graft function and no evidence of recurrent disease. MVT is an effective means of achieving complete gross resection of intra-abdominal malignancies in patients with multiple organ and vascular involvement.
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Affiliation(s)
- Eliza Lee
- Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA
| | - Nicole Hodgkinson
- Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA
| | - Rima Fawaz
- Division of Gastroenterology, Hepatology, & Nutrition, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA
| | - Khashayar Vakili
- Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA
| | - Heung Bae Kim
- Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA
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Rutter S, Morotti RA, Peterec S, Gallagher PG. Hepatic Malignancy in an Infant with Wolf-Hirschhorn Syndrome. Fetal Pediatr Pathol 2017; 36:256-262. [PMID: 28266898 DOI: 10.1080/15513815.2017.1293201] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
INTRODUCTION Wolf-Hirschhorn syndrome (WHS) is a contiguous gene syndrome involving deletions of the chromosome 4p16 region associated with growth failure, characteristic craniofacial abnormalities, cardiac defects, and seizures. CASE REPORT This report describes a six-month-old girl with WHS with growth failure and typical craniofacial features who died of complex congenital heart disease. Genetic studies revealed a 9.8 Mb chromosome 4p-terminal deletion. At autopsy, the liver was grossly unremarkable. Routine sampling and histologic examination revealed two hepatocellular nodular lesions with expanded cell plates and mild cytologic atypia. Immunohistochemical staining revealed these nodules were positive for glutamine synthetase and glypican 3, with increased Ki-67 signaling and diffuse CD34 expression in sinusoidal endothelium. These findings are consistent with hepatoblastoma or hepatocellular carcinoma. CONCLUSIONS A possible association between WHS and hepatic malignancy may be an important consideration in the care and management of WHS patients.
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Affiliation(s)
- Sara Rutter
- a Department of Pathology , Yale University School of Medicine , New Haven , Connecticut , USA
| | - Raffaella A Morotti
- a Department of Pathology , Yale University School of Medicine , New Haven , Connecticut , USA.,b Department of Pediatrics , Yale University School of Medicine , New Haven , Connecticut , USA
| | - Steven Peterec
- b Department of Pediatrics , Yale University School of Medicine , New Haven , Connecticut , USA
| | - Patrick G Gallagher
- a Department of Pathology , Yale University School of Medicine , New Haven , Connecticut , USA.,b Department of Pediatrics , Yale University School of Medicine , New Haven , Connecticut , USA.,c Department of Genetics , Yale University School of Medicine , New Haven , Connecticut , USA
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36
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Hiyama E, Hishiki T, Watanabe K, Ida K, Yano M, Oue T, Iehara T, Hoshino K, Koh K, Tanaka Y, Kurihara S, Ueda Y, Onitake Y. 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; 51:2053-2057. [PMID: 27712887 DOI: 10.1016/j.jpedsurg.2016.09.038] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2016] [Accepted: 09/12/2016] [Indexed: 11/19/2022]
Abstract
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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Affiliation(s)
- Eiso Hiyama
- Department of Pediatric Surgery, Hiroshima University Hospital, Hiroshima, 734-8551, Japan; Japanese Study Group for Pediatric Liver Tumor.
| | | | | | - Kohmei Ida
- Japanese Study Group for Pediatric Liver Tumor
| | | | | | | | - Ken Hoshino
- Japanese Study Group for Pediatric Liver Tumor
| | | | | | - Sho Kurihara
- Department of Pediatric Surgery, Hiroshima University Hospital, Hiroshima, 734-8551, Japan
| | - Yuka Ueda
- Department of Pediatric Surgery, Hiroshima University Hospital, Hiroshima, 734-8551, Japan
| | - Yoshiyuki Onitake
- Department of Pediatric Surgery, Hiroshima University Hospital, Hiroshima, 734-8551, Japan
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Kader MA, Essawy MG, Abdel Wahed SR, Alredy MM, Ismail AM, Abdel Hakeem GL, Riad KF. The utility of 64-multidetector computed tomography in the diagnosis and staging of hepatoblastoma patients. THE EGYPTIAN JOURNAL OF RADIOLOGY AND NUCLEAR MEDICINE 2016. [DOI: 10.1016/j.ejrnm.2016.07.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022] Open
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Bortel N, Armeanu-Ebinger S, Schmid E, Kirchner B, Frank J, Kocher A, Schiborr C, Warmann S, Fuchs J, Ellerkamp V. 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 2016; 6:40680-91. [PMID: 26515460 PMCID: PMC4747361 DOI: 10.18632/oncotarget.5673] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2015] [Accepted: 09/13/2015] [Indexed: 12/18/2022] Open
Abstract
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.
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Affiliation(s)
- Nicola Bortel
- Department of Pediatric Surgery and Pediatric Urology, University Hospital Tuebingen, D-72076 Tuebingen, Germany
| | - Sorin Armeanu-Ebinger
- Department of Pediatric Surgery and Pediatric Urology, University Hospital Tuebingen, D-72076 Tuebingen, Germany
| | - Evi Schmid
- Department of Pediatric Surgery and Pediatric Urology, University Hospital Tuebingen, D-72076 Tuebingen, Germany
| | - Bettina Kirchner
- Department of Pediatric Surgery and Pediatric Urology, University Hospital Tuebingen, D-72076 Tuebingen, Germany
| | - Jan Frank
- Institute of Biological Chemistry and Nutrition, University of Hohenheim, Division of Biofunctionality and Safety of Food, D-70599 Stuttgart, Germany
| | - Alexa Kocher
- Institute of Biological Chemistry and Nutrition, University of Hohenheim, Division of Biofunctionality and Safety of Food, D-70599 Stuttgart, Germany
| | - Christina Schiborr
- Institute of Biological Chemistry and Nutrition, University of Hohenheim, Division of Biofunctionality and Safety of Food, D-70599 Stuttgart, Germany
| | - Steven Warmann
- Department of Pediatric Surgery and Pediatric Urology, University Hospital Tuebingen, D-72076 Tuebingen, Germany
| | - Jörg Fuchs
- Department of Pediatric Surgery and Pediatric Urology, University Hospital Tuebingen, D-72076 Tuebingen, Germany
| | - Verena Ellerkamp
- Department of Pediatric Surgery and Pediatric Urology, University Hospital Tuebingen, D-72076 Tuebingen, Germany
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Abstract
Hepatoblastoma is rarely reported to metastasize to the brain. A comprehensive review of the literature was undertaken to characterize such patients and to examine the various therapies utilized to treat them. We identified 39 patients, including 1 previously unreported case from our institution. Although only 19 of these patients had much demographic information reported, it is notable that 24% (4/17) were older than 4 years at their original primary tumor diagnosis and 63% (7/11) had evidence of pulmonary metastases (at original diagnosis or recurrence) before the occurrence of brain metastasis. On the basis of the limited data published about this rare presentation and the known association of poor outcome with older age at diagnosis, we recommend additional neuroimaging in older hepatoblastoma patients when they present for evaluation of a pulmonary recurrence even when they are neurologically asymptomatic, with the aim of early identification and surgical resection of these lesions. The role of radiotherapy as an adjunct treatment for multiple cerebral lesions looks promising and needs to be explored further.
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40
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Pinto RB, Ramos ARL, Backes AN, dos Santos BJ, Provenzi VO, Carbonera MR, Roenick ML, dos Santos PPA, Falhauber F, de Souza MV, Bassols JV, Artigalás O. Hirschsprung disease and hepatoblastoma: case report of a rare association. SAO PAULO MED J 2016; 134:171-5. [PMID: 26465815 PMCID: PMC10496547 DOI: 10.1590/1516-3180.2014.9200311] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2014] [Revised: 07/07/2014] [Accepted: 11/03/2014] [Indexed: 01/01/2023] Open
Abstract
CONTEXT Hirschsprung disease is a developmental disorder of the enteric nervous system that is characterized by absence of ganglion cells in the distal intestine, and it occurs in approximately 1 in every 500,000 live births. Hepatoblastoma is a malignant liver neoplasm that usually occurs in children aged 6 months to 3 years, with a prevalence of 0.54 cases per 100,000. CASE REPORT A boy diagnosed with intestinal atresia in the first week of life progressed to a diagnosis of comorbid Hirschsprung disease. Congenital cataracts and sensorineural deafness were diagnosed. A liver mass developed and was subsequently confirmed to be a hepatoblastoma, which was treated by means of surgical resection of 70% of the liver volume and neoadjuvant chemotherapy (ifosfamide, cisplatin and doxorubicin). CONCLUSION It is known that Hirschsprung disease may be associated with syndromes predisposing towards cancer, and that hepatoblastoma may also be associated with certain congenital syndromes. However, co-occurrence of hepatoblastoma and Hirschsprung disease has not been previously described. We have reported a case of a male patient born with ileal atresia, Hirschsprung disease and bilateral congenital cataract who was later diagnosed with hepatoblastoma.
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Affiliation(s)
- Raquel Borges Pinto
- MD. Physician, Department of Pediatric Gastroenterology, Hospital da Criança Conceição, Grupo Hospitalar Conceição (GHC), Porto Alegre, Rio Grande do Sul, Brazil.
| | - Ana Regina Lima Ramos
- MD. Physician, Department of Pediatric Gastroenterology, Hospital da Criança Conceição, Grupo Hospitalar Conceição (GHC), Porto Alegre, Rio Grande do Sul, Brazil.
| | - Ariane Nadia Backes
- MD. Physician, Department of Pediatric Surgery, Hospital da Criança Conceição, Grupo Hospitalar Conceição (GHC), Porto Alegre, Rio Grande do Sul, Brazil.
| | - Beatriz John dos Santos
- MD. Physician, Department of Pediatric Gastroenterology, Hospital da Criança Conceição, Grupo Hospitalar Conceição (GHC), Porto Alegre, Rio Grande do Sul, Brazil.
| | - Valentina Oliveira Provenzi
- MD. Physician, Department of Pathological Anatomy, Hospital Nossa Senhora da Conceição, Grupo Hospitalar Conceição (GHC), Porto Alegre, Rio Grande do Sul, Brazil.
| | - Mário Rafael Carbonera
- MD. Physician, Department of Pediatric Surgery, Hospital da Criança Conceição, Grupo Hospitalar Conceição (GHC), Porto Alegre, Rio Grande do Sul, Brazil.
| | - Maria Lúcia Roenick
- MD. Resident, Department of Pediatric Surgery, Hospital da Criança Conceição, Grupo Hospitalar Conceição (GHC), Porto Alegre, Rio Grande do Sul, Brazil.
| | - Pedro Paulo Albino dos Santos
- MD. Physician, Department of Pediatric Oncology and Hematology, Hospital da Criança Conceição, Grupo Hospitalar Conceição (GHC), Porto Alegre, Rio Grande do Sul, Brazil.
| | - Fabrizia Falhauber
- MD. Physician, Department of Pediatric Oncology and Hematology, Hospital da Criança Conceição, Grupo Hospitalar Conceição (GHC), Porto Alegre, Rio Grande do Sul, Brazil.
| | - Meriene Viquetti de Souza
- MD. Resident, Department of Pediatrics, Hospital da Criança Conceição, Grupo Hospitalar Conceição (GHC), Porto Alegre, Rio Grande do Sul, Brazil.
| | - João Vicente Bassols
- MD. Physician, Department of Pediatric Surgery, Hospital da Criança Conceição, Grupo Hospitalar Conceição (GHC), Porto Alegre, Rio Grande do Sul, Brazil.
| | - Osvaldo Artigalás
- MD. Physician, Department of Medical Genetics, Hospital da Criança Conceição, Grupo Hospitalar Conceição (GHC), Porto Alegre, Rio Grande do Sul, Brazil.
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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; 50:2098-101. [PMID: 26388131 DOI: 10.1016/j.jpedsurg.2015.08.035] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2015] [Accepted: 08/24/2015] [Indexed: 11/24/2022]
Abstract
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.
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Felsted AE, Shi Y, Masand PM, Nuchtern JG, Goss JA, Vasudevan SA. Intraoperative ultrasound for liver tumor resection in children. J Surg Res 2015; 198:418-23. [PMID: 25940155 DOI: 10.1016/j.jss.2015.03.087] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2015] [Revised: 03/11/2015] [Accepted: 03/27/2015] [Indexed: 01/10/2023]
Abstract
BACKGROUND Primary hepatic neoplasms in children are rare tumors. All malignant and medically refractive benign primary pediatric liver tumors ultimately require surgical resection for cure. Accurate preoperative imaging including multidetector helical computerized tomography or magnetic resonance imaging (MRI) is necessary to determine resectability. In the literature intraoperative ultrasound (IOUS) has proven to be a vital adjunct to liver surgery in adults, but this is not well established in children. MATERIALS AND METHODS Between April 2003 and November 2014, children (<18-y-old) with a primary liver neoplasm, preoperatively evaluated with multidetector helical computerized tomography or MRI, who had IOUS used at the time of surgery were retrospectively reviewed. RESULTS Preoperative evaluation with high-resolution MRI and IOUS were discordant in 4 of 19 patients (21%). In one case, right hepatic vein involvement was not accurately assessed with MRI. Two cases showed tumor involvement in segment IV by MRI; however, IOUS revealed no medial segment involvement. The final patient had a large (>5 cm), solitary hepatic adenoma on MRI, but IOUS in this case revealed diffuse adenomatosis. The operative management was altered in three of these cases. CONCLUSIONS Although MRI can provide a detailed view of the hepatic anatomy and is an invaluable tool for preoperative planning for the pediatric patient with a primary liver neoplasm, IOUS may provide further and more up to date delineation of tumor extent and should be considered a crucial element in operative planning for hepatectomy in children.
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Affiliation(s)
- Amy E Felsted
- Division of Pediatric Surgery, Michael E. DeBakey Department of Surgery, Texas Children's Hospital Liver Tumor Center, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas
| | - Yan Shi
- Division of Pediatric Surgery, Michael E. DeBakey Department of Surgery, Texas Children's Hospital Liver Tumor Center, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas
| | - Prakash M Masand
- Department of Radiology, Texas Children's Hospital Liver Tumor Center, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas
| | - Jed G Nuchtern
- Division of Pediatric Surgery, Michael E. DeBakey Department of Surgery, Texas Children's Hospital Liver Tumor Center, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas
| | - John A Goss
- Division of Abdominal Transplantation, Michael E. DeBakey Department of Surgery, Texas Children's Hospital Liver Tumor Center, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas
| | - Sanjeev A Vasudevan
- Division of Pediatric Surgery, Michael E. DeBakey Department of Surgery, Texas Children's Hospital Liver Tumor Center, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas.
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Abstract
Children with cancer undergo a host of surgeries and procedures that require anesthesia during the various phases of the disease. A safe anesthetic plan includes consideration of the direct effects of tumor, toxic effects of chemotherapy and radiation therapy, the specifics of the surgical procedure, drug-drug interactions with chemotherapy agents, pain syndromes, and psychological status of the child. This article provides a comprehensive overview of the anesthetic management of the child with cancer, focuses on a systems-based approach to the impact from both tumor and its treatment in children, and presents a discussion of the relevant anesthetic considerations.
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Affiliation(s)
- Gregory J Latham
- Department of Anesthesiology and Pain Medicine, Seattle Children's Hospital, University of Washington School of Medicine, 4800 Sand Point Way Northeast, MB.11.500.3, Seattle, WA 98105, USA.
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Rapini N, Lidano R, Pietrosanti S, Vitiello G, Grimaldi C, Postorivo D, Nardone AM, Del Bufalo F, Brancati F, Manca Bitti ML. De novo 13q13.3-21.31 deletion involving RB1 gene in a patient with hemangioendothelioma of the liver. Ital J Pediatr 2014; 40:5. [PMID: 24433316 PMCID: PMC3896849 DOI: 10.1186/1824-7288-40-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2013] [Accepted: 12/12/2013] [Indexed: 01/29/2023] Open
Abstract
Interstitial deletions of the long arm of chromosome 13 (13q) are related with variable phenotypes, according to the size and the location of the deleted region. The main clinical features are moderate/severe mental and growth retardation, cranio-facial dysmorphism, variable congenital defects and increased susceptibility to tumors. Here we report a 3-year-old girl carrying a de novo 13q13.3-21.32 interstitial deletion. She showed developmental delay, growth retardation and mild dysmorphism including curly hair, high forehead, short nose, thin upper lip and long philtrum. An abnormal mass was surgically removed from her liver resulting in a hemangioendothelioma. Array analysis allowed us to define a deleted region of about 27.87 Mb, which includes the RB1 gene. This is the first report of a 13q deletion associated with infantile hemangioendothelioma of the liver.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Francesco Brancati
- Medical Genetics Unit, Policlinico Tor Vergata University Hospital, Viale Oxford, 81-00133 Rome, Italy.
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45
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Finegold MJ, López-Terrada DH. Hepatic Tumors in Childhood. PATHOLOGY OF PEDIATRIC GASTROINTESTINAL AND LIVER DISEASE 2014:547-614. [DOI: 10.1007/978-3-642-54053-0_14] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Allan BJ, Parikh PP, Diaz S, Perez EA, Neville HL, Sola JE. Predictors of survival and incidence of hepatoblastoma in the paediatric population. HPB (Oxford) 2013; 15:741-6. [PMID: 23600968 PMCID: PMC3791112 DOI: 10.1111/hpb.12112] [Citation(s) in RCA: 83] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2013] [Accepted: 03/17/2013] [Indexed: 12/12/2022]
Abstract
OBJECTIVES This study evaluates current trends in incidence, clinical outcomes and factors predictive of survival in children with hepatoblastoma (HB). METHODS The Surveillance, Epidemiology and End Results (SEER) database was queried for the period 1973-2009 for all patients aged <20 years with HB. RESULTS A total of 606 patients were identified. The age-adjusted incidence was 0.13 patients per 100 000 in 2009. An annual percentage change of 2.18% (95% confidence interval (CI) 1.10-3.27; P < 0.05) was seen over the study period. Overall survival rates at 5, 10 and 20 years were 63%, 61% and 59%, respectively. Ten-year survival rates significantly improved in patients with resectable disease who underwent operative treatment in comparison with those with non-resectable HB (86% versus 39%; P < 0.0001). Multivariate analysis showed surgical treatment (hazard ratio (HR) = 0.23, 95% CI 0.17-0.31; P < 0.0001), Hispanic ethnicity (HR = 0.61, 95% CI 0.43-0.89; P = 0.01), local disease at presentation (HR = 0.43, 95% CI 0.29-0.63; P < 0.0001) and age < 5 years (HR = 0.63, 95% CI 0.41-0.95; P < 0.03) to be independent prognostic factors of survival. CONCLUSIONS The incidence of paediatric HB has increased over time. Hepatoblastoma is almost exclusively seen in children aged < 5 years. When HB presents after the age of 5 years, the prognosis is most unfavourable. Tumour extirpation markedly improves survival in paediatric patients with local disease.
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Affiliation(s)
- Bassan J Allan
- Division of General Surgery, University of Miami Miller School of MedicineMiami, FL, USA
| | - Punam P Parikh
- Division of General Surgery, University of Miami Miller School of MedicineMiami, FL, USA
| | - Sofia Diaz
- Division of General Surgery, University of Miami Miller School of MedicineMiami, FL, USA
| | - Eduardo A Perez
- Division of Paediatric Surgery, DeWitt-Daughtry Family Department of Surgery, University of Miami Miller School of MedicineMiami, FL, USA
| | - Holly L Neville
- Division of Paediatric Surgery, DeWitt-Daughtry Family Department of Surgery, University of Miami Miller School of MedicineMiami, FL, USA
| | - Juan E Sola
- Division of Paediatric Surgery, DeWitt-Daughtry Family Department of Surgery, University of Miami Miller School of MedicineMiami, FL, USA
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Hiyama E. Current therapeutic strategies for childhood hepatic malignant tumors. Int J Clin Oncol 2013; 18:943-5. [PMID: 24057320 DOI: 10.1007/s10147-013-0607-9] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2013] [Indexed: 10/26/2022]
Abstract
The two main malignant hepatic tumors in children are hepatoblastomas (HBLs) and hepatocellular carcinomas (HCCs). The past two decades have brought significant improvement to the outcomes of children diagnosed with malignant hepatic tumors, especially HBL, due to improvements in diagnosis and treatment. Histological diagnosis is essential for differential diagnosis of these tumors. In surgery, liver resection has become a safe and secure technique because of progress in anatomical knowledge and surgical dissection; also liver transplantation has become widely used for unresectable tumors. Moreover, the introduction of effective chemotherapeutic regimens has significantly improved the survival of children with HBL due to an increase in the number of patients ultimately undergoing tumor resection, and a reduction in the incidence of post-surgical recurrence. These improvements are the result of multicenter cooperative trials conducted by the Japanese Study Group for Pediatric Liver Tumor, the Children's Oncology Group, and the International Childhood Liver Tumor Strategy Group, including work of the German Association of Pediatric Hematology and Oncology. This paper summarizes the results of these studies and calls on the current international collaboration study called the Children's Hepatic Tumors International Collaboration Project to establish global clinical research on childhood hepatic malignant tumors.
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Affiliation(s)
- Eiso Hiyama
- Department of Pediatric Surgery, Hiroshima University Hospital, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8551, Japan,
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Kelly DA, Bucuvalas JC, Alonso EM, Karpen SJ, Allen U, Green M, Farmer D, Shemesh E, McDonald RA. Long-term medical management of the pediatric patient after liver transplantation: 2013 practice guideline by the American Association for the Study of Liver Diseases and the American Society of Transplantation. Liver Transpl 2013; 19:798-825. [PMID: 23836431 DOI: 10.1002/lt.23697] [Citation(s) in RCA: 108] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2013] [Accepted: 06/15/2013] [Indexed: 12/15/2022]
Affiliation(s)
- Deirdre A Kelly
- Liver Unit, Birmingham Children's Hospital, National Health Service Trust, Birmingham, United Kingdom.
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Lin WC, Cheng CS, Lin CH. Spontaneous Regression of Infantile Hepatic Hemangioendothelioma. J Med Ultrasound 2013. [DOI: 10.1016/j.jmu.2013.04.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
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Abstract
We present a young patient with metastatic Ewing sarcoma that had hepatic lesions. As we were unaware of hepatic metastases in Ewing sarcoma, liver biopsy was performed. The pathologic findings were diagnostic of mesenchymal hamartoma of the liver. Surprisingly, the combined chemotherapy for metastatic sarcoma resulted in almost complete resolution of the hamartoma in the liver. This option may be useful in extreme cases when resection is not feasible.
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