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Wu Z, Xia F, Wang W, Zhang K, Fan M, Lin R. Worldwide burden of liver cancer across childhood and adolescence, 2000-2021: a systematic analysis of the Global Burden of Disease Study 2021. EClinicalMedicine 2024; 75:102765. [PMID: 39170941 PMCID: PMC11338123 DOI: 10.1016/j.eclinm.2024.102765] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2024] [Revised: 07/13/2024] [Accepted: 07/15/2024] [Indexed: 08/23/2024] Open
Abstract
Background Liver cancer is a significant contributor to the global disease burden, of which hepatoblastomas are the most common liver tumors in children, with 90% of cases occurring within the first 5 years of life. It is important for pediatricians and subspecialists in pediatric gastroenterology and hepatology to have knowledge of the epidemiology and incidence trends of pediatric hepatic cancer, despite its rarity. In the present study, we first provide estimates of the incidence and mortality burden of hepatoblastoma and liver cancer from 2000 to 2021 in the childhood and adolescence. Methods Liver cancer burden and its attributable risk factors were estimated using data from the Global Burden of Disease Study (GBD) 2021. Percentage change was estimated to show the trend of liver cancer estimates from 2000 to 2021. The age-standardized rate (ASR) and estimated annual percentage change (EAPC) were utilized for measuring hepatoblastomas incidence and deaths rate trends. In accordance with the GBD framework, 95% uncertainty intervals (UIs) for all estimates by averaging the data from 1000 draws, with the lower and upper bounds of the 95% UIs. Findings Globally, from 2000 to 2021 in the age 5-19 years group, the incidence cases and deaths cases due to liver cancer decreased from 2449.2 (95% UI: 2235.9-2689.8) to 1692.9 (95% UI: 1482.0-1992.5) and 2248.5 (95% UI: 2053.7-2474.9) to 1516.6 (95% UI: 1322.1-1797.9), respectively. Meanwhile, from 2000 to 2021 in the age 20-24 years group, the incidence cases and deaths cases due to liver cancer decreased from 1453.5 (95% UI: 1327.8-1609.4) to 1285.1 (95% UI: 1159.2-1447.2) and 1432.3 (95% UI: 1307.6-1585.7) to 1195.5 (95% UI: 1066.1-1355.2), respectively. In addition, the prevalence of liver cancer decreased from 41.9% (95% UI: 18.7%-64.7%) to 26.4% (95% UI: 14.2%-39.1%) in the age 5-19 years group, and 46.6% (95% UI: 42.8%-51.5%) to 36.5% (95% UI: 33.1%-40.9%) in the age 20-24 years. From 2000 to 2021, in the age group of 5-19 years, the proportion of liver cancer incidence due to hepatitis B has decreased from 42.2% to 37.9%, while the proportion due to hepatitis C has increased from 1.1% to 1.6%. Additionally, there has been an increase in the proportion of NASH-induced liver cancer incidence from 5.2% to 9.4%, and alcohol use induced liver cancer incidence has also increased from 0.5% to 0.7% over the same period. Globally, from 2000 to 2021, the incidence cases and deaths cases due to hepatoblastoma decreased from 6131.8 (95% UI: 5234.8-6961.9) to 4045.6 (95% UI: 3250-4995.8) and 4059.2 (95% UI: 3494.5-4621.2) to 2416 (95% UI: 1940.2-3022.5), respectively. There was some variation in age-related sex-specific patterns, the highest number of hepatoblastoma incidence cases occurred in children between 2 and 4 years old and females in the age range of 12 months to 9 years had a higher number of new cases. Importantly, the incidence of hepatoblastoma was started to increase sharply after the age of 1 month. Interpretation The results of the present study are significant for liver health policy and practice in childhood and adolescence. Differentiated intervention and outreach strategies based on age and gender would be necessary to reduce the impact of liver cancer. Early screening and interventions for hepatoblastoma is important especially in the population of under 9 years old. Funding This study was supported by the National Key R&D Program of China (grant numbers 2023YFC2307000), National Natural Science Foundation of China [grant numbers 82170571 and 81974068], China Postdoctoral Science Foundation (grant numbers 2023M741283).
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Affiliation(s)
- Zenghong Wu
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Fangnan Xia
- Biomedical Materials Engineering Research Center, Hubei Key Laboratory of Polymer Materials, Ministry-of-Education Key Laboratory for the Green Preparation and Application of Functional Materials, School of Materials Science & Engineering, State Key Laboratory of Biocatalysis and Enzyme Engineering, Hubei University, Wuhan, China
| | - Weijun Wang
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Kun Zhang
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Mengke Fan
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Rong Lin
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Sakamoto S, Harikrishnan S, Uchida H, Yanagi Y, Fukuda A, Kasahara M. Liver transplantation for pediatric liver malignancies. Liver Transpl 2024:01445473-990000000-00440. [PMID: 39172014 DOI: 10.1097/lvt.0000000000000470] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Accepted: 08/15/2024] [Indexed: 08/23/2024]
Abstract
In the last few decades, collaboration between international pediatric oncology groups has resulted in significant improvement in survival after liver transplantation (LT) for pediatric liver tumors, and LT has become the accepted standard of care for unresectable pediatric liver tumors-either living donor liver transplantation or deceased donor liver transplantation. Hepatoblastoma and HCC are the common pediatric liver malignancies treated by LT, and LT is now the accepted treatment modality for unresectable nonmetastatic cases. The long-term survival rate is more than 80% in hepatoblastoma transplants. Furthermore, with the advent of living donor liver transplantation, the waitlist mortality, availability of a better graft quality with shorter ischemic times, and performance of LT with the appropriate timing between chemotherapy have all improved. Up to 80% of pediatric HCCs are unresectable, and studies have shown that LT for pediatric HCC has better outcomes than liver resection. Furthermore, LT has also shown better results than liver resection for cases of HCC not meeting Milan criteria. Given the rarity of pediatric liver malignancies and challenges in optimal management, a multidisciplinary treatment approach, research models building on what is already known, and consideration of newer treatment modalities are required for further improving the treatment of pediatric liver malignancies.
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Affiliation(s)
- Seisuke Sakamoto
- Organ Transplantation Center, National Center for Child Health and Development, Setagaya-ku, Tokyo, Japan
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Nalwa A, Nakra T, Yadav R, Walia R, Agarwala S, Jana M, Jain D, Das P, Mathur SR, Iyer VK. Cytomorphology of paediatric hepatocellular carcinoma: A useful diagnostic adjunct. Cytopathology 2023; 34:479-488. [PMID: 37357840 DOI: 10.1111/cyt.13266] [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: 11/23/2022] [Revised: 05/26/2023] [Accepted: 06/09/2023] [Indexed: 06/27/2023]
Abstract
INTRODUCTION Hepatocellular carcinoma (HCC) is a common primary malignancy of the liver but is rare in the paediatric age group; thus, it may be misdiagnosed as the more common tumour, hepatoblastoma. Management varies in both these tumours, and pathological diagnosis thus plays an important role for definitive therapy. Only a few case reports available in the literature have described the cytological characteristics of paediatric HCC. The present study was thus planned to evaluate the cytomorphological features of paediatric HCC. METHODS Cases diagnosed with HCC on ultrasound-guided fine needle aspiration cytology over a period of 14 years were retrieved. The cases were evaluated for detailed cytological features including cellularity, architecture, sinusoidal wrapping, trabecular thickness, necrosis, anisonucleosis, chromatin, nucleoli, nuclear contours, bi- or multinucleation, intranuclear and intracytoplasmic inclusions, naked nuclei, extra-medullary haematopoiesis, monomorphism, and nuclear overlapping. RESULTS Twelve cases of HCC were included in the study. The median age at diagnosis was 10 years. Serum alpha-fetoprotein level was raised in most of them. Five of the 12 cases were characterised as moderately differentiated, three as poorly differentiated, two as well differentiated, and two as the fibrolamellar type of HCC. Cytohistological correlation was performed in seven cases. CONCLUSIONS Ultrasound-guided fine needle aspiration serves as a useful tool to diagnose paediatric HCC and differentiate it from other primary hepatic malignancies, especially hepatoblastoma which closely mimics HCC in this age group, as serum alpha protein levels and imaging findings are unable to distinguish these two tumours.
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Affiliation(s)
- Aasma Nalwa
- Department of Pathology, All India Institute of Medical Sciences, Jodhpur, India
| | - Tripti Nakra
- Department of Pathology, University College of Medical Sciences, University of Delhi, Delhi, India
| | - Rajni Yadav
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Ritika Walia
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Sandeep Agarwala
- Department of Paediatric Surgery, All India Institute of Medical Sciences, New Delhi, India
| | - Manisha Jana
- Department of Radiodiagnosis, All India Institute of Medical Sciences, New Delhi, India
| | - Deepali Jain
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Prasenjit Das
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Sandeep R Mathur
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Venkateswaran K Iyer
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
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Sharma R. Descriptive epidemiology of incidence and mortality of primary liver cancer in 185 countries: evidence from GLOBOCAN 2018. Jpn J Clin Oncol 2021; 50:1370-1379. [PMID: 32719873 DOI: 10.1093/jjco/hyaa130] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2020] [Accepted: 07/03/2020] [Indexed: 12/24/2022] Open
Abstract
PURPOSE This study aims to examine the burden of primary liver cancer in 185 countries in 2018. METHODS The estimates of incidence, mortality and prevalence of primary liver cancer were procured from GLOBOCAN 2018. The development status of a country was measured using the human development index-a composite indicator of income per capita, education and life expectancy. RESULTS Globally, primary liver cancer resulted in an estimated 781 631 deaths at age-standardized mortality rate of 8.5/100 000, and 841 080 cases were estimated to be diagnosed in 2018. Males accounted for 596 574 cases and 548 375 deaths, which is more than twice the burden of primary liver cancer in females (cases: 244 506; deaths: 233 456). The global age-standardized incidence rate was 9.3/100 000 in 2018, varying from Morocco (1.1/100 000) to Mongolia (93.7/100 000). There were remarkable variations in terms of age-standardized mortality rate, too, which ranged from 1/100 000 in Nepal to 75.4/100 000 in Mongolia. East Asia was the top region contributing 55.6% of global cases and 54.7% of global deaths. CONCLUSIONS Since majority of the primary liver cancer burden pertains to hepatocellular carcinoma and screening approaches are yet to be fully proven, the policy focus must be on prevention approaches through the hepatitis-B vaccine, early detection of hepatitis-C infection, reduced alcohol consumption, obesity control, reduced aflatoxin exposure and containment of other modifiable risk factors.
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Affiliation(s)
- Rajesh Sharma
- University School of Management and Entrepreneurship, Delhi Technological University, Delhi, India
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Hu H, Zhang W, Wang Y, Zhang Y, Yi Y, Gao Y, Chen L, Huang D. Prognostic analysis for children with hepatoblastoma with lung metastasis: A single-center analysis of 98 cases. Asia Pac J Clin Oncol 2020; 17:e191-e200. [PMID: 32920996 DOI: 10.1111/ajco.13421] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2019] [Accepted: 06/15/2020] [Indexed: 12/19/2022]
Abstract
AIMS To analyze the factors affecting the prognosis of hepatoblastoma (HB) with lung metastasis in children. METHODS The HB patients with lung metastases admitted to Beijing Tongren Hospital, Capital Medical University were collected. The clinical data, overall results, and prognostic factors were analyzed. Multivariate analysis was done by the Cox proportional hazards model for patients' prognosis. RESULTS Finally, 98 HB patients (64 boys and 34 girls) with lung metastasis met the inclusion criteria, in which 64 patients had lung metastases at diagnosis (median age, 22.3 months) and 34 patients developed lung metastases while on treatment (median time, 6.5 months). The survival time and 5-year survival rate of patients with standard treatment were significantly longer than that of without standard treatment (P < .001). The survival time and 3-year survival rate had no difference between patients underwent lung metastasectomy and without lung metastasectomy (P = .099), between different diagnosis time of lung metastasis in HB patients (P = .37), between each histology type (P = .313), and different PRETEXT stage (P = .353). While the survival time and 3-year survival rate of patients with lung metastasis alone were significantly longer than that of patients with extrapulmonary involvement (P = .007). Multivariate Cox proportional hazards model revealed that the lung metastasis accompanied with extrapulmonary involvement was a risk factor affecting prognosis (HR = 0.460, 95% CI 0.239-0.888). CONCLUSIONS For HB children with lung metastatic, extrapulmonary involvement might be a high-risk factor of prognosis and standardized treatment with lung metastasectomy might prolong the survival time of them.
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Affiliation(s)
- Huimin Hu
- Department of Pediatrics, Beijing Tongren Hospital, Capital Medical University, Beijing, P.R. China
| | - Weiling Zhang
- Department of Pediatrics, Beijing Tongren Hospital, Capital Medical University, Beijing, P.R. China
| | - Yizhuo Wang
- Department of Pediatrics, Beijing Tongren Hospital, Capital Medical University, Beijing, P.R. China
| | - Yi Zhang
- Department of Pediatrics, Beijing Tongren Hospital, Capital Medical University, Beijing, P.R. China
| | - You Yi
- Department of Pediatrics, Beijing Tongren Hospital, Capital Medical University, Beijing, P.R. China
| | - Yanan Gao
- Department of Pediatrics, Beijing Tongren Hospital, Capital Medical University, Beijing, P.R. China
| | - Liping Chen
- Department of Pediatrics, Beijing Tongren Hospital, Capital Medical University, Beijing, P.R. China
| | - Dongsheng Huang
- Department of Pediatrics, Beijing Tongren Hospital, Capital Medical University, Beijing, P.R. China
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D'Souza AM, Towbin AJ, Gupta A, Alonso M, Nathan JD, Bondoc A, Tiao G, Geller JI. Clinical heterogeneity of pediatric hepatocellular carcinoma. Pediatr Blood Cancer 2020; 67:e28307. [PMID: 32307899 DOI: 10.1002/pbc.28307] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2019] [Revised: 02/11/2020] [Accepted: 03/16/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is often a chemoresistant neoplasm with a poor prognosis. Pediatric HCC may reflect unique biological and clinical heterogeneity. PROCEDURE An IRB-approved retrospective institutional review of patients with HCC treated between 2004 and 2015 was undertaken. Clinical, radiographic, and histologic data were collected from all patients. RESULTS Thirty-two patients with HCC, median age 11.5 years (range 1-20) were identified. Seventeen patients had a genetic or anatomic predisposition. Histology was conventional HCC (25) and fibrolamellar HCC (7). Evans staging was 1 (12); 2 (1); 3 (10); 4 (9). Sixteen patients underwent resection at diagnosis and five patients after neoadjuvant chemotherapy. Surgical procedures included liver transplantation (LT, 11), hemihepatectomy (9), and segmentectomy (1). Eighteen patients had medical therapy (13 neoadjuvant, 5 adjuvant). Most common initial medical therapy included sorafenib alone (7) and cisplatin/doxorubicin-based therapy (8). Overall, 14 (43.8%) patients survived with a median follow-up of 58.8 months (range 26.5-157.6). Cause of death was most often linked to lack of primary tumor surgery (11). Of the survivors, Evans stage was 1 (11), 2 (1), and 3 (2, both treated with LT). Four of 18 patients (22%) who received medical therapy, 8 of 17 patients with a predisposition (47%), and 14 of 21 patients (66%) who underwent surgery remain alive. CONCLUSIONS Genetic and anatomic predisposing conditions were seen in over half of this cohort. Evans stage 1 or 2 disease was linked to improved survival. LT trended toward improved survival. Use of known chemotherapy agents may benefit a smaller group of pediatric HCC and warrants formal prospective study through cooperative group trials.
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Affiliation(s)
- Amber M D'Souza
- Division of Pediatric Hematology/Oncology, University of Illinois College of Medicine at Peoria, Peoria, Illinois
| | - Alexander J Towbin
- Department of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Anita Gupta
- Division of Pathology and Laboratory Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Maria Alonso
- Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Jaimie D Nathan
- Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Alex Bondoc
- Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Greg Tiao
- Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - James I Geller
- Division of Pediatric Hematology/Oncology, University of Illinois College of Medicine at Peoria, Peoria, Illinois
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Uzunova L, Bailie H, Murray MJ. Fifteen-minute consultation: A general paediatrician's guide to oncological abdominal masses. Arch Dis Child Educ Pract Ed 2019; 104:129-134. [PMID: 30733241 DOI: 10.1136/archdischild-2018-315270] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2018] [Revised: 11/20/2018] [Accepted: 01/10/2019] [Indexed: 11/03/2022]
Abstract
The identification of an abdominal mass in a child, either coincidental or symptomatic, may be due to a tumour. An abdominal tumour may present with life-threatening symptoms, requiring prompt assessment and management. Although the discovery of such a finding usually warrants inpatient transfer or outpatient referral to the tertiary oncology centre, the initial evaluation, management and communication with the family by the general paediatrician is crucial. A thorough history and examination, which includes an organised, structured approach to abdominal masses, is paramount. The anatomical location of the mass, age of the patient and the presence of any associated symptoms or signs must be considered together in order to formulate a list of potential differential diagnoses and guide the next appropriate investigations. This article aims to guide general paediatricians through the assessment and initial management of a child presenting with an abdominal mass suspected to be a tumour.
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Affiliation(s)
- Lena Uzunova
- Department of Paediatric Haematology and Oncology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK
| | - Helen Bailie
- Department of Paediatrics, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
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D'Souza AM, Shah R, Gupta A, Towbin AJ, Alonso M, Nathan JD, Bondoc A, Tiao G, Geller JI. Surgical management of children and adolescents with upfront completely resected hepatocellular carcinoma. Pediatr Blood Cancer 2018; 65:e27293. [PMID: 29968976 DOI: 10.1002/pbc.27293] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2018] [Revised: 05/13/2018] [Accepted: 05/30/2018] [Indexed: 12/14/2022]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is an aggressive malignant neoplasm that is often chemoresistant. Complete surgical resection remains the mainstay of therapy. The role of liver transplantation (LT) in pediatric HCC is in evolution, as is the role of adjuvant chemotherapy for stage I disease. METHODS A retrospective review of patients < 18 years of age with completely resected HCC treated with surgical intervention alone at our institution from 2004 to 2015 was conducted. RESULTS Twelve patients with a median age of 12 years (range = 1-17; number of females = 7) with upfront resected HCC (Evans stage I) were identified. Four patients had HCC without identifiable risk factors (fibrolamellar-HCC = 2; early HCC arising in focal nodular hyperplasia = 1, well-differentiated [wd] HCC = 1). Four patients had early or wd-HCC in the context of portosystemic shunts (Abernethy = 2; mesocaval shunt and portal vein thrombosis = 2). Four patients had moderate to wd-HCC in the context of pre-existing liver disease with cirrhosis (progressive familial intrahepatic cholestasis type-2 = 2, alpha-1 antitrypsin deficiency = 1, Alagille syndrome = 1). Seven patients underwent LT (multifocal = 5; solitary = 2); five exceeded Milan criteria (MC) by imaging. Five patients underwent complete resection (segmentectomy = 2; hemihepatectomy = 3). Ten patients received no adjuvant chemotherapy. All patients are alive without evidence of disease with a median follow-up of 54.1 months (range = 28.1-157.7 months). CONCLUSIONS Pediatric and adolescent patients with upfront, completely resected HCC can be effectively treated without chemotherapy. LT should be considered for nonmetastatic HCC, especially in the context of pre-existing chronic liver disease, even when the tumor exceeds MC. Distinct pediatric selection criteria are needed to identify patients most suitable for LT.
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Affiliation(s)
- Amber M D'Souza
- Division of Oncology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Rachana Shah
- Division of Oncology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Anita Gupta
- Division of Pathology and Laboratory Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Alexander J Towbin
- Department of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Maria Alonso
- Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Jaimie D Nathan
- Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Alex Bondoc
- Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Greg Tiao
- Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - James I Geller
- Division of Oncology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
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Khanna R, Verma SK. Pediatric hepatocellular carcinoma. World J Gastroenterol 2018; 24:3980-3999. [PMID: 30254403 PMCID: PMC6148423 DOI: 10.3748/wjg.v24.i35.3980] [Citation(s) in RCA: 88] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2018] [Revised: 07/11/2018] [Accepted: 08/01/2018] [Indexed: 02/06/2023] Open
Abstract
Pediatric hepatocellular carcinoma (HCC) is the second common malignant liver tumor in children after hepatoblastoma. It differs from the adult HCC in the etiological predisposition, biological behavior and lower frequency of cirrhosis. Perinatally acquired hepatitis-B virus, hepatorenal tyrosinemia, progressive familial intrahepatic cholestasis, glycogen storage disease, Alagille’s syndrome and congenital portosystemic shunts are important predisposing factors. Majority of children (87%) are older than 5 years of age. Following mass immunization against hepatitis-B, there has been a drastic fall in the incidence of new cases of pediatric HCC in the Asia-Pacific region. Management is targeted on complete surgical removal either by resection or liver transplantation. There is a trend towards improving survival of children transplanted for HCC beyond Milan criteria. Chemotherapeutic regimens do not offer good results but may be helpful for down-staging of advanced HCC. Surveillance of children with chronic liver diseases with ultrasound and alpha-fetoprotein may be helpful in timely detection, intervention and overall improvement in outcome of HCC.
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Affiliation(s)
- Rajeev Khanna
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi 110070, India
| | - Sanjeev Kumar Verma
- Department of Pediatrics, King George Medical University, Uttar Pradesh 226003, India
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Angelico R, Grimaldi C, Saffioti MC, Castellano A, Spada M. Hepatocellular carcinoma in children: hepatic resection and liver transplantation. Transl Gastroenterol Hepatol 2018; 3:59. [PMID: 30363724 DOI: 10.21037/tgh.2018.09.05] [Citation(s) in RCA: 155] [Impact Index Per Article: 22.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2018] [Accepted: 09/03/2018] [Indexed: 12/12/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is a rare malignancy in children and at the time of diagnosis up to 80% of pediatric HCC are unresectable due to large and multiple lesions. The majority of pediatric HCC occurs on a background of normal liver, and consequently the absence of concomitant chronic liver disease generally allows tolerating pre- and post-operative chemotherapy. Based on the large experiences of adult HCC and pediatric hepatoblastoma, in the last years a multidisciplinary aggressive treatment composed of surgical resection and chemotherapy (based on cisplatin and doxorubicin) has been proposed, improving patient outcomes and recurrence rate in children with HCC. However, the overall survival rate in children with HCC is not satisfactory yet; while the 5-year survival rate may achieve up to 70-80% in non-metastatic resectable HCC, it remains <20% in children with unresectable HCC. The mainstay of the pediatric HCC therapeutic strategy is the radical tumor resection, weather by hepatic resection or liver transplantation, nevertheless the best surgical approaches as well as the optimal neoadjuvant and adjuvant treatment are still under debate. Different strategies have been explored to convert unresectable HCC into resectable tumors by extending criteria for surgical treatment and/or associating multi-modal treatments, such as systemic and local-regional therapy, but universal recommendation needs to be defined yet. The purpose of this review is to outline the role of different surgical approaches, including hepatic resection and liver transplantation, in pediatric HCC with or without underlying chronic liver disease.
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Affiliation(s)
- Roberta Angelico
- Division of Abdominal Transplantation and Hepatobiliopancreatic Surgery, Bambino Gesù Children's Hospital IRCCS, Rome, Italy
| | - Chiara Grimaldi
- Division of Abdominal Transplantation and Hepatobiliopancreatic Surgery, Bambino Gesù Children's Hospital IRCCS, Rome, Italy
| | - Maria Cristina Saffioti
- Division of Abdominal Transplantation and Hepatobiliopancreatic Surgery, Bambino Gesù Children's Hospital IRCCS, Rome, Italy
| | - Aurora Castellano
- Division of Oncohematology, Bambino Gesù Children's Hospital IRCCS, Rome, Italy
| | - Marco Spada
- Division of Abdominal Transplantation and Hepatobiliopancreatic Surgery, Bambino Gesù Children's Hospital IRCCS, Rome, Italy
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LaQuaglia MJ, Kim HB, Fynn-Thompson F, Baird C, Vakili K. Resection of hepatic tumors with central venous and right atrial extension using cardiopulmonary bypass. JOURNAL OF PEDIATRIC SURGERY CASE REPORTS 2018. [DOI: 10.1016/j.epsc.2017.09.038] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
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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] [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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13
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Pediatric Hepatocellular Carcinoma, a Single Center Study from the South of Iran: Case Series. HEPATITIS MONTHLY 2017. [DOI: 10.5812/hepatmon.11837] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
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14
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Schmid I, von Schweinitz D. Pediatric hepatocellular carcinoma: challenges and solutions. J Hepatocell Carcinoma 2017; 4:15-21. [PMID: 28144610 PMCID: PMC5248979 DOI: 10.2147/jhc.s94008] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a very rare entity in children, making it nearly impossible to orchestrate Phase II/III studies even as multinational cooperative trials. In contrast to adults, nearly 50% of the children have a response (α-fetoprotein decline and/or tumor shrinkage) to chemotherapeutic agents such as cisplatin and doxorubicin (PLADO), demonstrating that HCC in childhood can be chemotherapy sensitive. As a result, the main treatment options in pediatric HCC focus on systemic drug therapies and resection as the central therapy. In nonmetastatic patients with complete resection upfront, the 5-year event-free survival and overall survival has reached 80%–90%. In almost all reported studies, children received adjuvant chemotherapy (mostly PLADO), but it has never been proven that postoperative chemotherapy is superior to observation. No data are available for the effects of sorafenib. The 3-year survival is <20% in children with unresectable HCC independent of the chemotherapy given preoperatively. Currently, PLADO in combination with sorafenib is recommended with the goal of achieving operability status. Alternatively, data are promising for the combination of sorafenib with gemcitabine and oxaliplatin. For children with nonresectable and nonmetastastic liver tumors, it has been shown that the Milan criteria regarding liver transplantation are not applicable – individual decisions have to be made. Transarterial chemoembolization could be offered to patients with chemotherapy-resistant liver tumors for palliative care or potentially to achieve surgical resectability, and therefore cure. Information about the feasibility or effects of new agents or approaches as discussed in adult HCC patients is not available for childhood HCC. Research has to be done for characterizing the molecular and genomic mechanisms of pediatric HCC to support the development of novel therapeutic approaches and the implementation of personalized medicine.
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Affiliation(s)
| | - Dietrich von Schweinitz
- Department of Pediatric Surgery, Dr. von Hauner Children's Hospital, Ludwig-Maximilians-University, Munich, Germany
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15
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Wang J, Mao Y, Liu Y, Chen Z, Chen M, Lao X, Li S. Hepatocellular Carcinoma in Children and Adolescents: Clinical Characteristics and Treatment. J Gastrointest Surg 2017; 21:1128-1135. [PMID: 28397025 PMCID: PMC5486687 DOI: 10.1007/s11605-017-3420-3] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2017] [Accepted: 03/30/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) occurs rarely in children and adolescents (C&A), and its clinical characteristics, prognostic factors, and treatment were rarely explored. METHODS This retrospective study focused on 65 HCC patients aged ≤20 years from August 1994 to August 2012. Cox regression models and Kaplan-Meier curves were used to investigate prognostic factors and compare overall survival (OS), respectively. RESULTS We found 61.5% of patients to have multiple tumors, 30.8% to have portal vein tumor thrombus, and 16.9% to have distant metastasis. Diameter of tumors was 10.2 ± 4.1 cm. OS at 5 years was 15.8%. Multivariate analyses showed initial treatment (P < 0.001) to be a predictor for OS. For moderate-stage HCC, the median OS of patients who underwent resection was longer than that of patients who underwent transarterial chemoembolization (TACE) or supportive treatment (ST) (P < 0.001). For advanced-stage HCC, the median OS of patients who underwent TACE was longer than that of patients who underwent ST (P = 0.045). CONCLUSIONS HCC in C&A tends to be more advanced than that in adults, and resection remains the mainstay of treatment for those patients. Moreover, compared with ST, TACE may benefit C&A with moderate- and advanced-stage HCC, which needs further study.
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Affiliation(s)
- Juncheng Wang
- 0000 0001 2360 039Xgrid.12981.33Department of Hepatobiliary Oncology, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, No. 651 Dongfeng Road East, Guangzhou, 510060 China
| | - Yize Mao
- 0000 0001 2360 039Xgrid.12981.33Department of Hepatobiliary Oncology, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, No. 651 Dongfeng Road East, Guangzhou, 510060 China
| | - Yongcheng Liu
- 0000 0001 2360 039Xgrid.12981.33Department of Hepatobiliary Oncology, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, No. 651 Dongfeng Road East, Guangzhou, 510060 China ,0000 0004 1759 700Xgrid.13402.34Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310020 China
| | - Zhenxin Chen
- 0000 0001 2360 039Xgrid.12981.33Department of Hepatobiliary Oncology, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, No. 651 Dongfeng Road East, Guangzhou, 510060 China
| | - Minshan Chen
- 0000 0001 2360 039Xgrid.12981.33Department of Hepatobiliary Oncology, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, No. 651 Dongfeng Road East, Guangzhou, 510060 China
| | - Xiangming Lao
- 0000 0001 2360 039Xgrid.12981.33Department of Hepatobiliary Oncology, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, No. 651 Dongfeng Road East, Guangzhou, 510060 China
| | - Shengping Li
- 0000 0001 2360 039Xgrid.12981.33Department of Hepatobiliary Oncology, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, No. 651 Dongfeng Road East, Guangzhou, 510060 China
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16
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Tajiri H, Takano T, Tanaka H, Ushijima K, Inui A, Miyoshi Y, Ozono K, Abukawa D, Endo T, Brooks S, Tanaka Y. Hepatocellular carcinoma in children and young patients with chronic HBV infection and the usefulness of alpha-fetoprotein assessment. Cancer Med 2016; 5:3102-3110. [PMID: 27748053 PMCID: PMC5119965 DOI: 10.1002/cam4.917] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2016] [Revised: 08/13/2016] [Accepted: 08/18/2016] [Indexed: 12/18/2022] Open
Abstract
The aims of the study were to elucidate the clinical characteristics of patients who developed hepatocellular carcinoma (HCC) related to persistent HBV infection since childhood and to investigate usefulness of assessing alpha‐fetoprotein (AFP) in this population. A nationwide multicenter survey of children with chronic HBV infection was performed. Among 548 patients, 15 patients developed HCC at the median age of 15 years (range 9–36), including 13 males and 2 females. A case–control comparison showed that HBeAg seroconversion and liver cirrhosis were associated with the occurrence of HCC. Of the 15 HCC patients, 5 were treated with interferon and none of them responded to interferon therapy as compared with 12 of the 17 responders in the control group. Of the 15 patients, 10 died and 9 of the 10 who died never visited any medical facilities until diagnosis of HCC, while the remaining 5 surviving patients never stopped their clinic visits. The usefulness of AFP assessment was shown by the findings that AFP levels were elevated in all HCC cases, that elevations in AFP levels were detected prior to the diagnosis in the surviving patients, and that sensitivity of AFP as a diagnostic test for HCC was very high among 40 patients including our 14 and an additional 26 collected from the literature. HBeAg seroconversion and liver cirrhosis are associated with the occurrence of HCC. Regular measurement of AFP might be helpful to watch for the occurrence of HCC when following children and young patients with chronic HBV infection since childhood
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Affiliation(s)
- Hitoshi Tajiri
- Department of Pediatrics, Osaka General Medical Center, Osaka, Japan
| | - Tomoko Takano
- Department of Pediatrics, Osaka General Medical Center, Osaka, Japan
| | - Hideo Tanaka
- Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan
| | - Kosuke Ushijima
- Department of Pediatrics, Kurume University Medical Center, Kurume, Japan
| | - Ayano Inui
- Department of Pediatric Hepatology and Gastroenterology, Saiseikai Yokohama City Tobu Hospital, Yokohama, Japan
| | - Yoko Miyoshi
- Department of Pediatrics, Osaka University Hospital, Suita, Japan
| | - Keiichi Ozono
- Department of Pediatrics, Osaka University Hospital, Suita, Japan
| | - Daiki Abukawa
- Department of Pediatrics, Miyagi Children's Hospital, Sendai, Japan
| | - Takeshi Endo
- Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Stephen Brooks
- Department of Microbiology/Immunology, State University of New York at Buffalo, New York
| | - Yasuhito Tanaka
- Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
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17
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Murawski M, Weeda VB, Maibach R, Morland B, Roebuck DJ, Zimmerman A, Casanova M, Perilongo G, Laithier V, Kebudi R, Scopinaro MJ, Shun A, Brichard B, de Camargo B, Childs M, Aronson DC, Czauderna P. Hepatocellular Carcinoma in Children: Does Modified Platinum- and Doxorubicin-Based Chemotherapy Increase Tumor Resectability and Change Outcome? Lessons Learned From the SIOPEL 2 and 3 Studies. J Clin Oncol 2016; 34:1050-6. [PMID: 26811523 DOI: 10.1200/jco.2014.60.2250] [Citation(s) in RCA: 57] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
INTRODUCTION The aim of this article is to present an experience of two prospective studies from the International Childhood Liver Tumor Strategy Group (SIOPEL 2 [S2] and SIOPEL [S3]) trials and to evaluate whether modified platinum- and doxorubicin-based chemotherapy is capable of increasing tumor resectability and changing patient outcomes. METHODS Between 1995 and 2006, 20 patients with hepatocellular carcinoma (HCC) were included in the S2 trial and 70 were included in the S3 trial. Eighty-five patients remained evaluable. RESULTS Response to preoperative chemotherapy was observed in 29 of 72 patients (40%) who did not have primary surgery, whereas 13 patients underwent upfront surgery. Thirty-three patients had a delayed resection. Thirty-nine tumors never became resectable. Complete tumor resection was achieved in 34 patients (40%), including seven of those treated with liver transplantation (LTX). After a median follow-up period of 75 months, 63 patients (74%) had an event (a progression during treatment, a relapse after treatment, or death from any cause). Sixty patients died. Twenty-three of 46 patients (50%) who underwent tumor resection died. Eighteen of 27 patients (63%) with complete tumor resection (without LTX) and 20 of 34 patients (59%) with LTX survived. Only one of seven patients (14%) with microscopically involved margins survived. Overall survival at 5 years was 22%. CONCLUSION Survival in pediatric HCC is more likely when complete tumor resection can be achieved. Intensification of platinum agents in the S2 and S3 trials has not resulted in improved survival. New treatment approaches in pediatric HCC should be postulated.
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Affiliation(s)
- Maciej Murawski
- Maciej Murawski and Piotr Czauderna, Medical University of Gdansk, Gdansk, Poland; Viola B. Weeda and Daniel C. Aronson, Emma Children's Hospital Academic Medical Center, Amsterdam, the Netherlands; Rudolf Maibach, International Breast Cancer Study Group Coordinating Center; Arthur Zimmerman, Institute of Pathology, Berne, Switzerland; Bruce Morland, Birmingham Children's Hospital, Birmingham; Derek J. Roebuck, Great Ormond Street Hospital, London; Margaret Childs, University of Nottingham, Nottingham, United Kingdom; Michela Casanova, National Cancer Institute, Milan; Giorgio Perilongo, University of Padova, Padova, Italy; Veronique Laithier, Centre Hospitalier Régional et Universitaire de Besançon, Besançon, France; Rejin Kebudi, İstanbul University, Oncology Institute, İstanbul, Turkey; Marcelo J. Scopinaro, Hospital de Pediatrı´a SAMIC J.P. Garrahan, Buenos Aires, Argentina; Albert Shun, Children's Hospital at Westmead, Sydney, Australia; Benedicte Brichard, Cliniques Universitaires Saint Luc, University of Louvain, Brussels, Belgium; and Beatriz de Camargo, Cancer Hospital A.C. Camargo, São Paulo, Brazil
| | - Víola B Weeda
- Maciej Murawski and Piotr Czauderna, Medical University of Gdansk, Gdansk, Poland; Viola B. Weeda and Daniel C. Aronson, Emma Children's Hospital Academic Medical Center, Amsterdam, the Netherlands; Rudolf Maibach, International Breast Cancer Study Group Coordinating Center; Arthur Zimmerman, Institute of Pathology, Berne, Switzerland; Bruce Morland, Birmingham Children's Hospital, Birmingham; Derek J. Roebuck, Great Ormond Street Hospital, London; Margaret Childs, University of Nottingham, Nottingham, United Kingdom; Michela Casanova, National Cancer Institute, Milan; Giorgio Perilongo, University of Padova, Padova, Italy; Veronique Laithier, Centre Hospitalier Régional et Universitaire de Besançon, Besançon, France; Rejin Kebudi, İstanbul University, Oncology Institute, İstanbul, Turkey; Marcelo J. Scopinaro, Hospital de Pediatrı´a SAMIC J.P. Garrahan, Buenos Aires, Argentina; Albert Shun, Children's Hospital at Westmead, Sydney, Australia; Benedicte Brichard, Cliniques Universitaires Saint Luc, University of Louvain, Brussels, Belgium; and Beatriz de Camargo, Cancer Hospital A.C. Camargo, São Paulo, Brazil
| | - Rudolf Maibach
- Maciej Murawski and Piotr Czauderna, Medical University of Gdansk, Gdansk, Poland; Viola B. Weeda and Daniel C. Aronson, Emma Children's Hospital Academic Medical Center, Amsterdam, the Netherlands; Rudolf Maibach, International Breast Cancer Study Group Coordinating Center; Arthur Zimmerman, Institute of Pathology, Berne, Switzerland; Bruce Morland, Birmingham Children's Hospital, Birmingham; Derek J. Roebuck, Great Ormond Street Hospital, London; Margaret Childs, University of Nottingham, Nottingham, United Kingdom; Michela Casanova, National Cancer Institute, Milan; Giorgio Perilongo, University of Padova, Padova, Italy; Veronique Laithier, Centre Hospitalier Régional et Universitaire de Besançon, Besançon, France; Rejin Kebudi, İstanbul University, Oncology Institute, İstanbul, Turkey; Marcelo J. Scopinaro, Hospital de Pediatrı´a SAMIC J.P. Garrahan, Buenos Aires, Argentina; Albert Shun, Children's Hospital at Westmead, Sydney, Australia; Benedicte Brichard, Cliniques Universitaires Saint Luc, University of Louvain, Brussels, Belgium; and Beatriz de Camargo, Cancer Hospital A.C. Camargo, São Paulo, Brazil
| | - Bruce Morland
- Maciej Murawski and Piotr Czauderna, Medical University of Gdansk, Gdansk, Poland; Viola B. Weeda and Daniel C. Aronson, Emma Children's Hospital Academic Medical Center, Amsterdam, the Netherlands; Rudolf Maibach, International Breast Cancer Study Group Coordinating Center; Arthur Zimmerman, Institute of Pathology, Berne, Switzerland; Bruce Morland, Birmingham Children's Hospital, Birmingham; Derek J. Roebuck, Great Ormond Street Hospital, London; Margaret Childs, University of Nottingham, Nottingham, United Kingdom; Michela Casanova, National Cancer Institute, Milan; Giorgio Perilongo, University of Padova, Padova, Italy; Veronique Laithier, Centre Hospitalier Régional et Universitaire de Besançon, Besançon, France; Rejin Kebudi, İstanbul University, Oncology Institute, İstanbul, Turkey; Marcelo J. Scopinaro, Hospital de Pediatrı´a SAMIC J.P. Garrahan, Buenos Aires, Argentina; Albert Shun, Children's Hospital at Westmead, Sydney, Australia; Benedicte Brichard, Cliniques Universitaires Saint Luc, University of Louvain, Brussels, Belgium; and Beatriz de Camargo, Cancer Hospital A.C. Camargo, São Paulo, Brazil
| | - Derek J Roebuck
- Maciej Murawski and Piotr Czauderna, Medical University of Gdansk, Gdansk, Poland; Viola B. Weeda and Daniel C. Aronson, Emma Children's Hospital Academic Medical Center, Amsterdam, the Netherlands; Rudolf Maibach, International Breast Cancer Study Group Coordinating Center; Arthur Zimmerman, Institute of Pathology, Berne, Switzerland; Bruce Morland, Birmingham Children's Hospital, Birmingham; Derek J. Roebuck, Great Ormond Street Hospital, London; Margaret Childs, University of Nottingham, Nottingham, United Kingdom; Michela Casanova, National Cancer Institute, Milan; Giorgio Perilongo, University of Padova, Padova, Italy; Veronique Laithier, Centre Hospitalier Régional et Universitaire de Besançon, Besançon, France; Rejin Kebudi, İstanbul University, Oncology Institute, İstanbul, Turkey; Marcelo J. Scopinaro, Hospital de Pediatrı´a SAMIC J.P. Garrahan, Buenos Aires, Argentina; Albert Shun, Children's Hospital at Westmead, Sydney, Australia; Benedicte Brichard, Cliniques Universitaires Saint Luc, University of Louvain, Brussels, Belgium; and Beatriz de Camargo, Cancer Hospital A.C. Camargo, São Paulo, Brazil
| | - Arthur Zimmerman
- Maciej Murawski and Piotr Czauderna, Medical University of Gdansk, Gdansk, Poland; Viola B. Weeda and Daniel C. Aronson, Emma Children's Hospital Academic Medical Center, Amsterdam, the Netherlands; Rudolf Maibach, International Breast Cancer Study Group Coordinating Center; Arthur Zimmerman, Institute of Pathology, Berne, Switzerland; Bruce Morland, Birmingham Children's Hospital, Birmingham; Derek J. Roebuck, Great Ormond Street Hospital, London; Margaret Childs, University of Nottingham, Nottingham, United Kingdom; Michela Casanova, National Cancer Institute, Milan; Giorgio Perilongo, University of Padova, Padova, Italy; Veronique Laithier, Centre Hospitalier Régional et Universitaire de Besançon, Besançon, France; Rejin Kebudi, İstanbul University, Oncology Institute, İstanbul, Turkey; Marcelo J. Scopinaro, Hospital de Pediatrı´a SAMIC J.P. Garrahan, Buenos Aires, Argentina; Albert Shun, Children's Hospital at Westmead, Sydney, Australia; Benedicte Brichard, Cliniques Universitaires Saint Luc, University of Louvain, Brussels, Belgium; and Beatriz de Camargo, Cancer Hospital A.C. Camargo, São Paulo, Brazil
| | - Michela Casanova
- Maciej Murawski and Piotr Czauderna, Medical University of Gdansk, Gdansk, Poland; Viola B. Weeda and Daniel C. Aronson, Emma Children's Hospital Academic Medical Center, Amsterdam, the Netherlands; Rudolf Maibach, International Breast Cancer Study Group Coordinating Center; Arthur Zimmerman, Institute of Pathology, Berne, Switzerland; Bruce Morland, Birmingham Children's Hospital, Birmingham; Derek J. Roebuck, Great Ormond Street Hospital, London; Margaret Childs, University of Nottingham, Nottingham, United Kingdom; Michela Casanova, National Cancer Institute, Milan; Giorgio Perilongo, University of Padova, Padova, Italy; Veronique Laithier, Centre Hospitalier Régional et Universitaire de Besançon, Besançon, France; Rejin Kebudi, İstanbul University, Oncology Institute, İstanbul, Turkey; Marcelo J. Scopinaro, Hospital de Pediatrı´a SAMIC J.P. Garrahan, Buenos Aires, Argentina; Albert Shun, Children's Hospital at Westmead, Sydney, Australia; Benedicte Brichard, Cliniques Universitaires Saint Luc, University of Louvain, Brussels, Belgium; and Beatriz de Camargo, Cancer Hospital A.C. Camargo, São Paulo, Brazil
| | - Giorgio Perilongo
- Maciej Murawski and Piotr Czauderna, Medical University of Gdansk, Gdansk, Poland; Viola B. Weeda and Daniel C. Aronson, Emma Children's Hospital Academic Medical Center, Amsterdam, the Netherlands; Rudolf Maibach, International Breast Cancer Study Group Coordinating Center; Arthur Zimmerman, Institute of Pathology, Berne, Switzerland; Bruce Morland, Birmingham Children's Hospital, Birmingham; Derek J. Roebuck, Great Ormond Street Hospital, London; Margaret Childs, University of Nottingham, Nottingham, United Kingdom; Michela Casanova, National Cancer Institute, Milan; Giorgio Perilongo, University of Padova, Padova, Italy; Veronique Laithier, Centre Hospitalier Régional et Universitaire de Besançon, Besançon, France; Rejin Kebudi, İstanbul University, Oncology Institute, İstanbul, Turkey; Marcelo J. Scopinaro, Hospital de Pediatrı´a SAMIC J.P. Garrahan, Buenos Aires, Argentina; Albert Shun, Children's Hospital at Westmead, Sydney, Australia; Benedicte Brichard, Cliniques Universitaires Saint Luc, University of Louvain, Brussels, Belgium; and Beatriz de Camargo, Cancer Hospital A.C. Camargo, São Paulo, Brazil
| | - Veronique Laithier
- Maciej Murawski and Piotr Czauderna, Medical University of Gdansk, Gdansk, Poland; Viola B. Weeda and Daniel C. Aronson, Emma Children's Hospital Academic Medical Center, Amsterdam, the Netherlands; Rudolf Maibach, International Breast Cancer Study Group Coordinating Center; Arthur Zimmerman, Institute of Pathology, Berne, Switzerland; Bruce Morland, Birmingham Children's Hospital, Birmingham; Derek J. Roebuck, Great Ormond Street Hospital, London; Margaret Childs, University of Nottingham, Nottingham, United Kingdom; Michela Casanova, National Cancer Institute, Milan; Giorgio Perilongo, University of Padova, Padova, Italy; Veronique Laithier, Centre Hospitalier Régional et Universitaire de Besançon, Besançon, France; Rejin Kebudi, İstanbul University, Oncology Institute, İstanbul, Turkey; Marcelo J. Scopinaro, Hospital de Pediatrı´a SAMIC J.P. Garrahan, Buenos Aires, Argentina; Albert Shun, Children's Hospital at Westmead, Sydney, Australia; Benedicte Brichard, Cliniques Universitaires Saint Luc, University of Louvain, Brussels, Belgium; and Beatriz de Camargo, Cancer Hospital A.C. Camargo, São Paulo, Brazil
| | - Rejin Kebudi
- Maciej Murawski and Piotr Czauderna, Medical University of Gdansk, Gdansk, Poland; Viola B. Weeda and Daniel C. Aronson, Emma Children's Hospital Academic Medical Center, Amsterdam, the Netherlands; Rudolf Maibach, International Breast Cancer Study Group Coordinating Center; Arthur Zimmerman, Institute of Pathology, Berne, Switzerland; Bruce Morland, Birmingham Children's Hospital, Birmingham; Derek J. Roebuck, Great Ormond Street Hospital, London; Margaret Childs, University of Nottingham, Nottingham, United Kingdom; Michela Casanova, National Cancer Institute, Milan; Giorgio Perilongo, University of Padova, Padova, Italy; Veronique Laithier, Centre Hospitalier Régional et Universitaire de Besançon, Besançon, France; Rejin Kebudi, İstanbul University, Oncology Institute, İstanbul, Turkey; Marcelo J. Scopinaro, Hospital de Pediatrı´a SAMIC J.P. Garrahan, Buenos Aires, Argentina; Albert Shun, Children's Hospital at Westmead, Sydney, Australia; Benedicte Brichard, Cliniques Universitaires Saint Luc, University of Louvain, Brussels, Belgium; and Beatriz de Camargo, Cancer Hospital A.C. Camargo, São Paulo, Brazil
| | - Marcelo J Scopinaro
- Maciej Murawski and Piotr Czauderna, Medical University of Gdansk, Gdansk, Poland; Viola B. Weeda and Daniel C. Aronson, Emma Children's Hospital Academic Medical Center, Amsterdam, the Netherlands; Rudolf Maibach, International Breast Cancer Study Group Coordinating Center; Arthur Zimmerman, Institute of Pathology, Berne, Switzerland; Bruce Morland, Birmingham Children's Hospital, Birmingham; Derek J. Roebuck, Great Ormond Street Hospital, London; Margaret Childs, University of Nottingham, Nottingham, United Kingdom; Michela Casanova, National Cancer Institute, Milan; Giorgio Perilongo, University of Padova, Padova, Italy; Veronique Laithier, Centre Hospitalier Régional et Universitaire de Besançon, Besançon, France; Rejin Kebudi, İstanbul University, Oncology Institute, İstanbul, Turkey; Marcelo J. Scopinaro, Hospital de Pediatrı´a SAMIC J.P. Garrahan, Buenos Aires, Argentina; Albert Shun, Children's Hospital at Westmead, Sydney, Australia; Benedicte Brichard, Cliniques Universitaires Saint Luc, University of Louvain, Brussels, Belgium; and Beatriz de Camargo, Cancer Hospital A.C. Camargo, São Paulo, Brazil
| | - Albert Shun
- Maciej Murawski and Piotr Czauderna, Medical University of Gdansk, Gdansk, Poland; Viola B. Weeda and Daniel C. Aronson, Emma Children's Hospital Academic Medical Center, Amsterdam, the Netherlands; Rudolf Maibach, International Breast Cancer Study Group Coordinating Center; Arthur Zimmerman, Institute of Pathology, Berne, Switzerland; Bruce Morland, Birmingham Children's Hospital, Birmingham; Derek J. Roebuck, Great Ormond Street Hospital, London; Margaret Childs, University of Nottingham, Nottingham, United Kingdom; Michela Casanova, National Cancer Institute, Milan; Giorgio Perilongo, University of Padova, Padova, Italy; Veronique Laithier, Centre Hospitalier Régional et Universitaire de Besançon, Besançon, France; Rejin Kebudi, İstanbul University, Oncology Institute, İstanbul, Turkey; Marcelo J. Scopinaro, Hospital de Pediatrı´a SAMIC J.P. Garrahan, Buenos Aires, Argentina; Albert Shun, Children's Hospital at Westmead, Sydney, Australia; Benedicte Brichard, Cliniques Universitaires Saint Luc, University of Louvain, Brussels, Belgium; and Beatriz de Camargo, Cancer Hospital A.C. Camargo, São Paulo, Brazil
| | - Benedicte Brichard
- Maciej Murawski and Piotr Czauderna, Medical University of Gdansk, Gdansk, Poland; Viola B. Weeda and Daniel C. Aronson, Emma Children's Hospital Academic Medical Center, Amsterdam, the Netherlands; Rudolf Maibach, International Breast Cancer Study Group Coordinating Center; Arthur Zimmerman, Institute of Pathology, Berne, Switzerland; Bruce Morland, Birmingham Children's Hospital, Birmingham; Derek J. Roebuck, Great Ormond Street Hospital, London; Margaret Childs, University of Nottingham, Nottingham, United Kingdom; Michela Casanova, National Cancer Institute, Milan; Giorgio Perilongo, University of Padova, Padova, Italy; Veronique Laithier, Centre Hospitalier Régional et Universitaire de Besançon, Besançon, France; Rejin Kebudi, İstanbul University, Oncology Institute, İstanbul, Turkey; Marcelo J. Scopinaro, Hospital de Pediatrı´a SAMIC J.P. Garrahan, Buenos Aires, Argentina; Albert Shun, Children's Hospital at Westmead, Sydney, Australia; Benedicte Brichard, Cliniques Universitaires Saint Luc, University of Louvain, Brussels, Belgium; and Beatriz de Camargo, Cancer Hospital A.C. Camargo, São Paulo, Brazil
| | - Beatriz de Camargo
- Maciej Murawski and Piotr Czauderna, Medical University of Gdansk, Gdansk, Poland; Viola B. Weeda and Daniel C. Aronson, Emma Children's Hospital Academic Medical Center, Amsterdam, the Netherlands; Rudolf Maibach, International Breast Cancer Study Group Coordinating Center; Arthur Zimmerman, Institute of Pathology, Berne, Switzerland; Bruce Morland, Birmingham Children's Hospital, Birmingham; Derek J. Roebuck, Great Ormond Street Hospital, London; Margaret Childs, University of Nottingham, Nottingham, United Kingdom; Michela Casanova, National Cancer Institute, Milan; Giorgio Perilongo, University of Padova, Padova, Italy; Veronique Laithier, Centre Hospitalier Régional et Universitaire de Besançon, Besançon, France; Rejin Kebudi, İstanbul University, Oncology Institute, İstanbul, Turkey; Marcelo J. Scopinaro, Hospital de Pediatrı´a SAMIC J.P. Garrahan, Buenos Aires, Argentina; Albert Shun, Children's Hospital at Westmead, Sydney, Australia; Benedicte Brichard, Cliniques Universitaires Saint Luc, University of Louvain, Brussels, Belgium; and Beatriz de Camargo, Cancer Hospital A.C. Camargo, São Paulo, Brazil
| | - Margaret Childs
- Maciej Murawski and Piotr Czauderna, Medical University of Gdansk, Gdansk, Poland; Viola B. Weeda and Daniel C. Aronson, Emma Children's Hospital Academic Medical Center, Amsterdam, the Netherlands; Rudolf Maibach, International Breast Cancer Study Group Coordinating Center; Arthur Zimmerman, Institute of Pathology, Berne, Switzerland; Bruce Morland, Birmingham Children's Hospital, Birmingham; Derek J. Roebuck, Great Ormond Street Hospital, London; Margaret Childs, University of Nottingham, Nottingham, United Kingdom; Michela Casanova, National Cancer Institute, Milan; Giorgio Perilongo, University of Padova, Padova, Italy; Veronique Laithier, Centre Hospitalier Régional et Universitaire de Besançon, Besançon, France; Rejin Kebudi, İstanbul University, Oncology Institute, İstanbul, Turkey; Marcelo J. Scopinaro, Hospital de Pediatrı´a SAMIC J.P. Garrahan, Buenos Aires, Argentina; Albert Shun, Children's Hospital at Westmead, Sydney, Australia; Benedicte Brichard, Cliniques Universitaires Saint Luc, University of Louvain, Brussels, Belgium; and Beatriz de Camargo, Cancer Hospital A.C. Camargo, São Paulo, Brazil
| | - Daniel C Aronson
- Maciej Murawski and Piotr Czauderna, Medical University of Gdansk, Gdansk, Poland; Viola B. Weeda and Daniel C. Aronson, Emma Children's Hospital Academic Medical Center, Amsterdam, the Netherlands; Rudolf Maibach, International Breast Cancer Study Group Coordinating Center; Arthur Zimmerman, Institute of Pathology, Berne, Switzerland; Bruce Morland, Birmingham Children's Hospital, Birmingham; Derek J. Roebuck, Great Ormond Street Hospital, London; Margaret Childs, University of Nottingham, Nottingham, United Kingdom; Michela Casanova, National Cancer Institute, Milan; Giorgio Perilongo, University of Padova, Padova, Italy; Veronique Laithier, Centre Hospitalier Régional et Universitaire de Besançon, Besançon, France; Rejin Kebudi, İstanbul University, Oncology Institute, İstanbul, Turkey; Marcelo J. Scopinaro, Hospital de Pediatrı´a SAMIC J.P. Garrahan, Buenos Aires, Argentina; Albert Shun, Children's Hospital at Westmead, Sydney, Australia; Benedicte Brichard, Cliniques Universitaires Saint Luc, University of Louvain, Brussels, Belgium; and Beatriz de Camargo, Cancer Hospital A.C. Camargo, São Paulo, Brazil
| | - Piotr Czauderna
- Maciej Murawski and Piotr Czauderna, Medical University of Gdansk, Gdansk, Poland; Viola B. Weeda and Daniel C. Aronson, Emma Children's Hospital Academic Medical Center, Amsterdam, the Netherlands; Rudolf Maibach, International Breast Cancer Study Group Coordinating Center; Arthur Zimmerman, Institute of Pathology, Berne, Switzerland; Bruce Morland, Birmingham Children's Hospital, Birmingham; Derek J. Roebuck, Great Ormond Street Hospital, London; Margaret Childs, University of Nottingham, Nottingham, United Kingdom; Michela Casanova, National Cancer Institute, Milan; Giorgio Perilongo, University of Padova, Padova, Italy; Veronique Laithier, Centre Hospitalier Régional et Universitaire de Besançon, Besançon, France; Rejin Kebudi, İstanbul University, Oncology Institute, İstanbul, Turkey; Marcelo J. Scopinaro, Hospital de Pediatrı´a SAMIC J.P. Garrahan, Buenos Aires, Argentina; Albert Shun, Children's Hospital at Westmead, Sydney, Australia; Benedicte Brichard, Cliniques Universitaires Saint Luc, University of Louvain, Brussels, Belgium; and Beatriz de Camargo, Cancer Hospital A.C. Camargo, São Paulo, Brazil.
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Hepatocellular Carcinoma in the Pediatric Population: A Population Based Clinical Outcomes Study Involving 257 Patients from the Surveillance, Epidemiology, and End Result (SEER) Database (1973-2011). HPB SURGERY : A WORLD JOURNAL OF HEPATIC, PANCREATIC AND BILIARY SURGERY 2015; 2015:670728. [PMID: 26663981 PMCID: PMC4667027 DOI: 10.1155/2015/670728] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/16/2015] [Accepted: 10/29/2015] [Indexed: 02/06/2023]
Abstract
Introduction. Hepatocellular carcinoma (HCC) is a rare pediatric cancer accounting for 0.5% of all pediatric malignancies. This study examines a large cohort of HCC patients in an effort to define the factors impacting clinical outcomes in pediatric HCC patients compared to adults. Methods. Demographic and clinical data on 63,771 HCC patients (257 pediatric patients ≤ 19 and 63,514 adult patients age ≥ 20) were abstracted from the SEER database (1973–2011). Results. HCC was more common among males (59.5% pediatric and 75.1% adults) and Caucasians (50.4% and 50.5%), p < 0.05. Children more often presented with fibrolamellar variant HCC (24.1% versus 0.3%, p = 0.71) and advanced HCC, including distant disease (33.1% versus 20.8%, p < 0.001), and tumors > 4 cm in size (79.6% versus 62.0%, p = 0.02). Pediatric HCC patients undergoing surgery (13.107 versus 8.324 years, p < 0.001) had longer survival than adult HCC patients. Overall mortality was lower (65.8% versus 82.0%, p < 0.001) in the pediatric HCC group. Conclusion. HCC is a rare pediatric malignancy that presents most often as an advanced tumor, >4 cm in Caucasian males. Children with HCC achieve significantly longer mean overall survival compared to adults with HCC, primarily attributable to the more favorable fibrolamellar histologic variant, and more aggressive surgical intervention, which significantly improves survival.
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19
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Allan BJ, Wang B, Davis JS, Parikh PP, Perez EA, Neville HL, Sola JE. A review of 218 pediatric cases of hepatocellular carcinoma. J Pediatr Surg 2014; 49:166-71; discussion 171. [PMID: 24439603 DOI: 10.1016/j.jpedsurg.2013.09.050] [Citation(s) in RCA: 62] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2013] [Accepted: 09/30/2013] [Indexed: 11/27/2022]
Abstract
PURPOSE This study evaluates the incidence trends and clinical outcomes of children with hepatocellular carcinoma (HCC) and assesses factors predictive of patient survival. METHODS The Surveillance, Epidemiology, and End Results registry was queried from 1973 to 2009 for all patients between ages 0 and 19 with primary HCC. Demographics, tumor histology, surgical intervention, and patient survival were collected. RESULTS Overall, 218 patients were identified. The annual age-adjusted incidence was 0.05 cases per 100,000 in 2009. Fibrolamellar subtype tumors were exclusive to children >5years old and exhibited greater survival compared to non-fibrolamellar subtype (57% vs. 28%, respectively, p=0.002). Tumor extirpation for patients with resectable disease significantly improved overall survival at 5years compared to no surgery (60% vs. 0%, respectively, p<0.0001). Overall 5-, 10- and 20-year survival for the entire cohort was 24%, 23%, and 8%, respectively. Independent prognostic factors of lower mortality according to multivariate analysis were surgical resection (hazard ratio (HR)=0.18), non-Hispanic ethnicity (HR=0.52), and local disease at presentation (HR=0.46). CONCLUSION Over the past four decades, the incidence of HCC has remained relatively stable. Children of Hispanic ethnicity have high mortality rates. However, HCC resection for curative intent significantly improves outcomes.
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Affiliation(s)
- Bassan J Allan
- Department of Surgery, Division of Pediatric Surgery, DeWitt-Daughtry Family, University of Miami Miller School of Medicine, Miami, FL 33136, USA
| | - Bo Wang
- Department of Surgery, Division of Pediatric Surgery, DeWitt-Daughtry Family, University of Miami Miller School of Medicine, Miami, FL 33136, USA
| | - James S Davis
- Department of Surgery, Division of Pediatric Surgery, DeWitt-Daughtry Family, University of Miami Miller School of Medicine, Miami, FL 33136, USA
| | - Punam P Parikh
- Department of Surgery, Division of Pediatric Surgery, DeWitt-Daughtry Family, University of Miami Miller School of Medicine, Miami, FL 33136, USA
| | - Eduardo A Perez
- Department of Surgery, Division of Pediatric Surgery, DeWitt-Daughtry Family, University of Miami Miller School of Medicine, Miami, FL 33136, USA
| | - Holly L Neville
- Department of Surgery, Division of Pediatric Surgery, DeWitt-Daughtry Family, University of Miami Miller School of Medicine, Miami, FL 33136, USA
| | - Juan E Sola
- Department of Surgery, Division of Pediatric Surgery, DeWitt-Daughtry Family, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
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20
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McAteer JP, Goldin AB, Healey PJ, Gow KW. Surgical treatment of primary liver tumors in children: outcomes analysis of resection and transplantation in the SEER database. Pediatr Transplant 2013; 17:744-50. [PMID: 23992390 DOI: 10.1111/petr.12144] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/28/2013] [Indexed: 12/20/2022]
Abstract
Adjusted survival outcomes following hepatic resection and transplantation for pediatric liver tumors have not been compared. To address this question, we conducted a retrospective cohort study using the SEER registry. While SEER lacks certain specifics regarding staging, chemotherapy, comorbidities, and recurrence, important hypothesis-generating data are available and were analyzed using Kaplan-Meier statistics and Cox proportional hazards regression. All SEER patients under the age of 20 yr undergoing surgery for HB (n = 318) or HCC (n = 80) between 1998 and 2009 were included. Of HB patients, 83.3% underwent resection and 16.7% transplantation. Advanced disease, vascular invasion, and satellite lesions were more common among transplant patients. Unadjusted five-yr survival was equivalent, as was the adjusted hazard of death for transplant relative to resection (HR = 0.58, p = 0.63). Of HCC patients, 75.0% underwent resection and 25.0% transplantation. Transplant patients had a higher prevalence of vascular invasion and satellite lesions. Five-yr survival was 53.4% after resection and 85.3% after transplant, and the adjusted hazard of death was significantly lower after transplantation (HR = 0.05, p = 0.045). While transplantation is generally reserved for unresectable tumors, the favorable survival seen in HCC patients suggests that liberalized transplant criteria might improve survival, although further prospective data are needed.
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Affiliation(s)
- Jarod P McAteer
- Division of Pediatric General and Thoracic Surgery, Seattle Children's Hospital, Seattle, WA, USA; Department of Surgery, University of Washington School of Medicine, Seattle, WA, USA
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21
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McAteer JP, Goldin AB, Healey PJ, Gow KW. Hepatocellular carcinoma in children: epidemiology and the impact of regional lymphadenectomy on surgical outcomes. J Pediatr Surg 2013; 48:2194-201. [PMID: 24210185 DOI: 10.1016/j.jpedsurg.2013.05.007] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2013] [Revised: 05/02/2013] [Accepted: 05/03/2013] [Indexed: 12/19/2022]
Abstract
BACKGROUND Factors influencing survival in children with HCC have not been studied. The objective of this study was to identify prognostic factors in pediatric HCC, and to determine whether regional lymphadenectomy is associated with improved survival. METHODS We performed a retrospective cohort study using the Surveillance, Epidemiology and End Results (SEER) registry. All patients <20 years old diagnosed with HCC from 1973-2009 were included. Disease-specific survival was compared using Kaplan-Meier statistics and Cox proportional-hazards regression. RESULTS We identified 238 patients (139 Male: 99 Female). Overall, 112 (47%) received an operation (resection/transplantation). Observed mortality and adjusted hazard of disease-specific death was greater for females (HR=2.07, p=0.013) and older children. Among operative patients, 44% were documented to have a regional lymphadenectomy. Although demographic factors did not differ between lymphadenectomy and non-lymphadenectomy groups, patients who underwent lymphadenectomy had a greater proportion of metastatic disease (24% vs. 15%) and fibrolamellar HCC (53% vs. 31%). Five-year survival for lymphadenectomy patients was superior to non-lymphadenectomy (70% vs. 57%). Adjusted mortality for lymphadenectomy was also improved relative to non-lymphadenectomy (HR=0.26, p=0.013). CONCLUSIONS HCC in children is associated with poor survival, especially among children older than 4 years and girls. In surgical candidates, regional lymphadenectomy may be associated with improved survival.
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Affiliation(s)
- Jarod P McAteer
- Division of Pediatric General and Thoracic Surgery, Seattle Children's Hospital, Seattle, WA 98105, USA; Department of Surgery, University of Washington School of Medicine, Seattle, WA 98195, USA.
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22
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Clinical characteristics and outcome of hepatocellular carcinoma in children and adolescents. Pediatr Surg Int 2013; 29:763-70. [PMID: 23794023 DOI: 10.1007/s00383-013-3334-4] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/11/2013] [Indexed: 02/07/2023]
Abstract
PURPOSE Hepatocellular carcinoma (HCC) rarely occurs in children and adolescents and has been reported to be highly hepatitis B related more than 10 years ago. However, after global vaccination for hepatitis B virus (HBV), the characteristics and outcome of pediatric HCC remain undefined. METHODS Patients with HCC admitted from 2004 to 2010 were retrospectively reviewed in a large tertiary hospital. RESULTS 45 (1.97 %) pediatric HCC were diagnosed (age ≤18 years), with predominantly male patients (93.3 %). 32 (71.1 %) children were HBV positive, 30 of whom had vertical transmission from their mothers. HBV positivity was associated with liver cirrhosis and portal vein invasion, and thus compromised survival. Advanced disease prevented surgical resection due to large tumor size (>10 cm, 66.7 %), early metastasis (24.4 %), bilateral involvement (57.8 %) and portal vein invasion (46.7 %). The median survival for resectable, transarterial chemotherapy and embolization and untreated patients was 28.6, 4 and 5 months, respectively (p < 0.001). Patients with distal metastasis had significantly poorer survival rate than those without metastasis (p < 0.001). CONCLUSION Screening of children whose mothers are HBV carriers is important in early detection of pediatric HCC. HBV-associated HCC in pediatric patients, especially in endemic areas, should be detected earlier for more resectability and improvement of surgical prognosis.
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Hoh A, Dewerth A, Vogt F, Wenz J, Baeuerle PA, Warmann SW, Fuchs J, Armeanu-Ebinger S. The activity of γδ T cells against paediatric liver tumour cells and spheroids in cell culture. Liver Int 2013; 33:127-36. [PMID: 23088518 DOI: 10.1111/liv.12011] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2012] [Accepted: 08/13/2012] [Indexed: 12/22/2022]
Abstract
BACKGROUND Chemoresistance and advanced tumour stage at time of diagnosis are the major reasons for poor treatment results in hepatoblastoma (HB) and paediatric hepatocellular carcinoma (HCC). Positive results with transplantation of liver and bone marrow revealed the impact of the immune system on the treatment of liver malignancies. AIM Cytotoxic-immune-cells-like natural killer (NK) and T cells are major player in the defence against developing tumours. This study aimed to specifically analyse the ability of ex-vivo expanded γδ T cells to recognise and lyse HB and HCC cell lines in coculture assays. METHODS Cell viability after treatment with γδ T cells was evaluated with two HB (HUH6 and HepT1) and one HCC cell line (HC-AFW1) using a MTT-based cytotoxicity assay. The binding of T cells to target cells was monitored using immunofluorescence microscopy. RESULTS Incubation of hepatic tumour cell lines with γδ T cells led to a significant decrease in tumour cell viability. This was enhanced by zoledronic acid and histone deacetylase inhibitors. MT110, an EpCAM/CD3-bispecific BiTE antibody could bluntly enhance tumour cell lysis close to completion. γδ T cells efficiently interacted with HB and HCC cells in a spheroid culture model. CONCLUSION Bispecific antibodies such as MT110 might be used to intensify the antitumoural effect of γδ T cells in context of adoptive immune cell transfer. Optimised immunotherapeutic strategies might therefore improve the outcome of high risk hepatoblastoma and hepatocellular carcinoma.
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MESH Headings
- Antibodies, Bispecific/pharmacology
- Antigens, Neoplasm/immunology
- CD3 Complex/immunology
- Carcinoma, Hepatocellular/immunology
- Carcinoma, Hepatocellular/pathology
- Cell Adhesion Molecules/immunology
- Cell Line, Tumor
- Cell Survival
- Coculture Techniques
- Cytotoxicity, Immunologic/drug effects
- Diphosphonates/pharmacology
- Epithelial Cell Adhesion Molecule
- Hepatoblastoma/immunology
- Hepatoblastoma/pathology
- Histone Deacetylase Inhibitors/pharmacology
- Humans
- Imidazoles/pharmacology
- Liver Neoplasms/immunology
- Liver Neoplasms/pathology
- Lymphocyte Activation/drug effects
- Microscopy, Fluorescence
- Receptors, Antigen, T-Cell, gamma-delta/immunology
- Single-Chain Antibodies/pharmacology
- Spheroids, Cellular
- T-Lymphocytes/drug effects
- T-Lymphocytes/immunology
- Zoledronic Acid
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Affiliation(s)
- Alexander Hoh
- Department of Paediatric Surgery and Urology, University Childreǹs Hospital, Tuebingen, Germany
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Duigenan S, Anupindi SA, Nimkin K. Imaging of multifocal hepatic lesions in pediatric patients. Pediatr Radiol 2012; 42:1155-68; quiz 1285. [PMID: 22565297 DOI: 10.1007/s00247-012-2400-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2011] [Revised: 02/25/2012] [Accepted: 03/05/2012] [Indexed: 02/08/2023]
Abstract
Imaging plays a vital role in detection and characterization of multifocal liver lesions in children. Numerous causes for these lesions exist, including benign and malignant neoplasms, infectious lesions, and congenital and inflammatory conditions. The imaging spectrum of multifocal liver lesions in children is presented with emphasis on key imaging features, differential diagnoses and helpful relevant clinical features.
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Affiliation(s)
- Shauna Duigenan
- Division of Pediatric Radiology, Massachusetts General Hospital, Boston, MA, USA.
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25
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Abstract
Liver tumors in children can be classified into benign or malignant; some of the benign lesions can have the potential of malignant transformation, and therefore the therapeutic approach may change. These neoplasms account for nearly 1-2% of all pediatric tumors and they have gained significant attention in the last decades due to data suggesting that the incidence may be increasing 5% annually. We know that with new and improved imaging modalities some of these lesions may be detected more often than before. Recent studies showed that liver cancer represented 2% of malignancies in infants by 1980s and this was doubled in incidence to 4% in the following 10 yr. In this review our aim is to discuss all primary liver tumors in children with attention to their clinicopathological and immunohistochemical features followed by the current standard of care.
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Affiliation(s)
- Sukru Emre
- Department of Surgery, Yale University School of Medicine, Yale, New Haven, CT, USA.
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26
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Schmid I, Häberle B, Albert MH, Corbacioglu S, Fröhlich B, Graf N, Kammer B, Kontny U, Leuschner I, Scheel-Walter HG, Scheurlen W, Werner S, Wiesel T, von Schweinitz D. Sorafenib and cisplatin/doxorubicin (PLADO) in pediatric hepatocellular carcinoma. Pediatr Blood Cancer 2012; 58:539-44. [PMID: 21922643 DOI: 10.1002/pbc.23295] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2011] [Accepted: 07/06/2011] [Indexed: 01/14/2023]
Abstract
PURPOSE Overall survival is poor in children with primary unresectable hepatocellular carcinoma. Sorafenib has been shown to significantly improve progression-free survival in adult hepatocellular carcinoma (HCC) patients. We evaluated the experience of PLADO (cisplatin 80 mg/m(2) /day, doxorubicin 2 × 30 mg/m(2) /day) in combination with sorafenib in pediatric HCC patients. PATIENTS AND METHODS Clinical data of 12 patients (7-16 years), 7 with unresectable tumor, were retrospectively assessed. RESULTS In total 6/12 (50%) patients are in complete remission after a median follow-up of 20 months (4 with PLADO/sorafenib/resection, 2 with liver transplantation after local relapse). Of the seven patients with unresectable tumor, PLADO/sorafenib resulted in partial response (PR) in four, stable disease (SD) in two, and progression in one. Three are alive in CR after complete resection after 12 (alternative therapy after two cycles PLADO/sorafenib), 12 and 18 months (six cycles PLADO/sorafenib), respectively. All four patients with elevated alpha-fetoprotein levels had a marked drop after two cycles. Of the five patients with primary complete tumor resection one is alive disease-free at 27 months. Four had local or metastatic relapses (13, 7, 12, and 13 months), two of whom were rescued by liver transplantation (CR after 25 and 32 months). The main toxicity attributable to sorafenib was a hand-foot skin reaction (HFSR) in seven patients. CONCLUSION Sorafenib in combination with PLADO may be a promising approach in pediatric HCC; HFSR was the most important toxicity. Data based on prospective studies are needed to evaluate pharmacokinetics, resectability rates, and survival in pediatric HCC treated with sorafenib.
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Affiliation(s)
- Irene Schmid
- Department of Pediatric Hematology and Oncology, Children's Hospital of the Ludwig-Maximilians-University, Munich, Germany.
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Romano F, Stroppa P, Bravi M, Casotti V, Lucianetti A, Guizzetti M, Sonzogni A, Colledan M, D'Antiga L. Favorable outcome of primary liver transplantation in children with cirrhosis and hepatocellular carcinoma. Pediatr Transplant 2011; 15:573-9. [PMID: 21797955 DOI: 10.1111/j.1399-3046.2011.01528.x] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The outcome of HCC after transplantation (OLT) in children is not well known. Unfavorable features based on adult reports may lead to contraindicate OLT even in children. We reviewed a cohort of children with cirrhosis and HCC to evaluate their outcome after primary transplantation. We considered children with cirrhosis and HCC who had a primary OLT. We retrospectively recorded demographic, medical and surgical features, and MC as predictors of outcome. Among 456 children transplanted in the last 15 yr, 10 (2%), median age at diagnosis 1.8 yr (range 0.5-7.2), had HCC in biliary atresia (3), BSEP deficiency (3), tyrosinemia type 1 (2), complications of choledocal cyst and glycogen storage disease type IV (1 each). At HCC discovery, median AFP was 2322 ng/mL (3-35,000), high or rising in 9/10 patients. Six patients were outside the MC. Median time on the waiting list was 38 days (1-152). Two patients died from early complications of OLT. In the other eight patients, there was no tumor recurrence after a median follow-up of four yr. Children with cirrhosis may develop HCC at a very young age. The outcome appears excellent even outside MC. Primary liver transplantation is advisable for children with cirrhosis, HCC, and no extrahepatic disease.
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Affiliation(s)
- Fabrizio Romano
- Department of Surgical Science, S. Gerardo Hospital, Milan, Italy
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Abstract
Management of pediatric liver tumors has significantly improved over the last 2 decades. The management options for hepatocelluar carcinoma (HCC) are not well defined. In the pediatric context, the main clinical aims are to reduce chemotherapy toxicity (predominantly ototoxicity and nephrotoxicity) in children treated for hepatoblastoma and to investigate additional modes of treatment for HCC. An increasing number of children develop HCC in the background of chronic liver disease, and screening methods need to be better observed.
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Affiliation(s)
- Nedim Hadzic
- King's College Hospital Denmark Hill, London SE5 9RS, UK.
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Chung EM, Lattin GE, Cube R, Lewis RB, Marichal-Hernández C, Shawhan R, Conran RM. From the Archives of the AFIP: Pediatric Liver Masses: Radiologic-Pathologic Correlation Part 2. Malignant Tumors. Radiographics 2011; 31:483-507. [DOI: 10.1148/rg.312105201] [Citation(s) in RCA: 138] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
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Rasalkar DD, Chu WCW, Cheng FWT, Hui SK, Ling SC, Li CK. A pictorial review of imaging of abdominal tumours in adolescence. Pediatr Radiol 2010; 40:1552-61; quiz 1589-90. [PMID: 20602098 DOI: 10.1007/s00247-010-1738-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2010] [Revised: 04/09/2010] [Accepted: 05/09/2010] [Indexed: 10/19/2022]
Abstract
Neoplastic abdominal tumours, particularly those originating from embryonal tissue (such as hepatoblastoma and nephroblastoma) and neural crest cells (such as neuroblastoma), are well-documented in young children. Neoplasms of adulthood, most commonly carcinoma of different visceral organs, are also well-documented. Abdominal tumours in adolescence constitute a distinct pathological group. The radiological features of some of these tumours have been described only in isolated reports. The purpose of this pictorial essay was to review the imaging findings of various kinds of abdominal tumours in adolescent patients (with an age range of 10-16 years) who presented to the Children Cancer Center of our institution in the past 15 years. Some tumours, though rare, have characteristic imaging appearances (especially in CT) that enable an accurate diagnosis before definite histological confirmation.
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Affiliation(s)
- Darshana D Rasalkar
- Department of Diagnostic Radiology and Organ Imaging, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong, China
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Caruso S, Mamone G, Marrone G, Milazzo M, Carollo V, Miraglia R, Maruzzelli L, Pasta A, Minervini MI, Spada M, Riva S, Luca A, Gridelli B. Focal liver diseases in neonatal and pediatric liver transplant candidates: a pictorial essay. Clin Transplant 2009; 24:592-8. [PMID: 19888996 DOI: 10.1111/j.1399-0012.2009.01139.x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
The aim of this review is to present the wide spectrum of common and uncommon focal liver diseases affecting neonatal and pediatric liver transplant candidates, analyzed using ultrasonography (US), 16- or 64-multidetector row helical CT (MDCT) and 1.5-T magnetic resonance (MR) fast imaging. Correlation of imaging findings and explanted liver or histology is illustrated in representative cases. Associated uncommon congenital anomalies are shown.
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Affiliation(s)
- Settimo Caruso
- Department of Radiology, Istituto Mediterraneo Trapianti e Terapie ad Alta Specializzazione (IsMeTT), Palermo, Italy.
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Ismail H, Broniszczak D, Kaliciński P, Markiewicz-Kijewska M, Teisseyre J, Stefanowicz M, Szymczak M, Dembowska-Bagińska B, Kluge P, Perek D, Kościesza A, Dzik E, Lembas A, Teisserye M. Liver transplantation in children with hepatocellular carcinoma. Do Milan criteria apply to pediatric patients? Pediatr Transplant 2009; 13:682-92. [PMID: 19496985 DOI: 10.1111/j.1399-3046.2009.01062.x] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
HCC constitutes 25-30% of primary malignant liver tumors in children. Conventional surgical excision is not possible in more than 50% of patients. LTx has recently become an important therapeutic option for adults and children with primary liver tumors. The aim of this study was a retrospective analysis of the clinical and pathological data of children with HCC treated with LTx in relation to Milan criteria assessed at diagnosis and then immediately before transplantation, in comparison with a group of patients treated conventionally. Between 1990 and 2007 we have treated 21 children diagnosed with HCC. Patients were divided into two groups: group I, 10 children treated conventionally and group II, 11 children treated with LTx regardless of previous therapy. The outcome of our patients treated conventionally with resection and chemotherapy is very poor--the disease-free survival rate is 30%. In contrast, despite that only 3 children having fulfilled adult Milan criteria, early clinical results of LTx are much superior. Total hepatectomy followed by LTx is the main treatment option for the majority of children with HCC. Decisions on the type of surgical treatment is made individually, but very early in the course of treatment.
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Affiliation(s)
- H Ismail
- Departments of Pediatric Surgery and Organ Transplantation, Children's Memorial Health Institute, Warsaw, Poland.
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Liu TT, Yi CS, Chou ASB, Lee MC, Chen MC, Wang LY, Lin HH, Hu CT. Comparison Between the CLIP and Okuda Staging Systems for Prediction of Survival Time of Patients with Hepatocellular Carcinoma in Eastern Taiwan. Tzu Chi Med J 2009. [DOI: 10.1016/s1016-3190(09)60006-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022] Open
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Patterns of hepatoblastoma and hepatocellular carcinoma in children after universal hepatitis B vaccination in taiwan: a report from a single institution in southern Taiwan. J Pediatr Hematol Oncol 2009; 31:91-6. [PMID: 19194190 DOI: 10.1097/mph.0b013e31818b3784] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
BACKGROUND To retrospectively evaluate clinical features, treatment, and outcome of patients with hepatoblastoma (HB) and hepatocellular carcinoma (HCC). METHODS From January 1994 to December 2007, 16 patients of HB and 13 cases of HCC were reviewed. RESULTS The mean age of HB patients was much younger than HCC patients (1.2 vs. 11.5 y). There was an 84.6% positive rate for hepatitis B surface antigen in HCC, but none for HB. Mean serum alpha-fetoprotein level was higher with HCC (654,158 ng/mL) than the HB patients (352,843 ng/mL), especially higher in HCC with lung metastasis. Among the HB patients, 12 (75%) had thrombocytosis and 6 (37.5%) had microcytic anemia with high or normal ferritin, whereas only 3 of 13 with HCC (23.1%) had thrombocytosis and none had microcytic anemia. All HBs were resectable either before or after chemotherapy, but only 4 (30.8%) HCCs were resectable. Five-year disease-free survival rate was significantly higher in HB (87%) than in HCC (30%, P<0.001). CONCLUSIONS Hepatitis B infection was still the most important factor associated with HCC in children even after the national vaccination program against hepatitis B. Extreme thrombocytosis, anemia, alpha-fetoprotein levels are important factors associated with difference in long-term outcomes in children with HB and HCC.
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Abstract
Hepatocellular carcinoma (HCC) is a rare pediatric neoplasm exceptionally reported in infants and fibrolamellar hepatocarcinoma (FLC) a HCC variant. Controversy exists whether FLC has a better prognosis than classic HCC, although recent studies of children and young adults with FLC did not report a better outcome. We present a 4-month-old male infant without any related metabolic or infectious disease who developed a metastatic and multifocal FLC. Serum alpha-fetoprotein determinations were always normal. Induction chemotherapy using cisplatin and Adriamycin resulted in a partial response, however, refractory disease developed and regional metastasis precluded surgical resection. The child died from tumoral progression.
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37
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Abstract
Imaging is a standard part of the evaluation of pediatric liver disease. Advances in MR imaging have improved detection, characterization, and staging of hepatic lesions. This article addresses the MR imaging appearances of various focal hepatic lesions that can present in children. Techniques for performing hepatic MR imaging also are reviewed.
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Affiliation(s)
- Marilyn J Siegel
- Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 South Kingshighway Boulevard, St. Louis, MO 63110, USA.
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38
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Sex hormone influence on hepatitis in young male A/JCr mice infected with Helicobacter hepaticus. Infect Immun 2008; 76:4071-8. [PMID: 18559427 DOI: 10.1128/iai.00401-08] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023] Open
Abstract
Hepatitis B virus (HBV), the leading cause of human hepatocellular carcinoma, is especially virulent in males infected at an early age. Likewise, the murine liver carcinogen Helicobacter hepaticus is most pathogenic in male mice infected before puberty. We used this model to investigate the influence of male sex hormone signaling on infectious hepatitis. Male A/JCr mice were infected with H. hepaticus or vehicle at 4 weeks and randomized into surgical and pharmacologic treatment groups. Interruption of androgen pathways was confirmed by hormone measurements, histopathology, and liver gene and Cyp4a protein expression. Castrated males and those receiving the competitive androgen receptor antagonist flutamide had significantly less severe hepatitis as determined by histologic activity index than intact controls at 4 months. Importantly, the powerful androgen receptor agonist dihydrotestosterone did not promote hepatitis. No effect on hepatitis was evident in males treated with the 5alpha-reductase inhibitor dutasteride, the peroxisome proliferator-activated receptor-alpha agonist bezafibrate, or the nonsteroidal anti-inflammatory drug flufenamic acid. Consistent with previous observations of hepatitis-associated liver-gender disruption, transcriptional alterations involved both feminine (cytochrome P450 4a14) and masculine (cytochrome P450 4a12 and trefoil factor 3) genes, as well gender-neutral (H19 fetal liver mRNA, lipocalin 2, and ubiquitin D) genes. Hepatitis was associated with increased unsaturated C(18) long-chain fatty acids (oleic acid and linoleic acid) relative to saturated stearic acid. Our results indicate that certain forms of androgen interruption can inhibit H. hepaticus-induced hepatitis in young male mice, whereas androgen receptor agonism does not worsen disease. This raises the possibility of targeted hormonal therapy in young male patients with childhood-acquired HBV.
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Abstract
Two patients with solid tumors were treated with 21-day continuous infusion topotecan as palliation therapy. Case 1: A 10-year-old girl was diagnosed with progressive, metastatic hepatocellular carcinoma. Twenty-one-day continuous infusion topotecan was started and she has had a partial response. Case 2: A 17-year-old girl developed a malignant fibrous histiocytoma as a second malignant neoplasm. After partial resection and failure of multiagent chemotherapy, she started continuous infusion topotecan and was disease-free for 58 months when she died of pneumonia. These cases suggest that topotecan given as 21-day continuous infusion is efficacious for palliation care.
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Abstract
Kasai portoenterostomy (PE) increases the survival for children with biliary atresia (BA) and consequently postpones subsequential liver transplantation. All long-term survivors, however, develop complications of biliary cirrhosis. We report a case of hepatocellular carcinoma (HCC) in a 19-year-old male patient with BA and Kasai PE. The preoperative abdominal ultrasound and magnetic resonance imaging showed a large hepatic mass (diameter 10 cm). The serum alpha-fetoprotein level was within normal range. Pathologic findings of the mass, after orthotopic liver transplantation, demonstrated a well-differentiated HCC (T1N0M0). HCC is a rare complication of BA, but will intensively impair the survival. Therefore, clinicians should be alert to the development of HCC in this very young patient group. Repeated sequential magnetic resonance imaging of the native liver in patients with Kasai PE is necessary to monitor possible malignant transformation of liver nodules that may potentially develop as a result of chronic cholestatic liver disease.
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41
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Beaunoyer M, Vanatta JM, Ogihara M, Strichartz D, Dahl G, Berquist WE, Castillo RO, Cox KL, Esquivel CO. Outcomes of transplantation in children with primary hepatic malignancy. Pediatr Transplant 2007; 11:655-60. [PMID: 17663690 DOI: 10.1111/j.1399-3046.2007.00751.x] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
HBL and HCC are the most common hepatic malignancies in children. The role of OLT in children with HCC is still a matter of debate. The aim of this study was to review our experience of OLT for HCC. Medical records of patients (<18 yr) who underwent OLT for HCC were reviewed and compared to children who underwent OLT for HBL and for indications other than malignancy. There were 25 patients: HCC (10 cases) and HBL (15 cases). The actuarial patient survival for HCC at one and five yr was 100% and 83.3%, for the HBL group the survival was 86.7% at both one and five yr, and for indications (n=377) other than malignancy the patient survival for pediatric OLT at our center was 87.7% and 84.7% at one and five yr, respectively. The actuarial recurrence free survival at five yr was 83.3% for HCC and 66.8% for HBL. In conclusion, OLT is a good therapeutic modality for children with HCC and HBL.
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Affiliation(s)
- Mona Beaunoyer
- Divisions of Transplantation, Lucile Salter Packard Children's Hospital and Stanford University School of Medicine, Stanford, CA 94304, USA
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Wang JD, Chang TK, Chen HC, Jan SL, Huang FL, Chi CS, Lin CC. Pediatric liver tumors: initial presentation, image finding and outcome. Pediatr Int 2007; 49:491-6. [PMID: 17587274 DOI: 10.1111/j.1442-200x.2007.02384.x] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Few reports have been carried out on the characteristics of pediatric liver tumors. METHODS A retrospective study of 57 patients diagnosed with liver tumors from 1989 through 2004 was conducted. They were classified into groups; 10 benign, 33 primary malignant and 14 metastatic liver tumors. Their demographics, initial presentations, laboratory data, image findings and outcomes were investigated and compared. RESULTS Hepatocellular carcinoma (HCC) with 91% hepatitis B virus-related, constituted 23 of 33 primary malignant liver tumors and had the poorest survival rate. Initially, 70% of patients with primary malignant liver tumors were at disseminated stages. All of HCC and 88% of hepatoblastoma had elevated serum levels of aphal-fetoprotein. However, abnormal liver function tests as alanine aminotransferase, total bilirubin, albumin and alkaline phosphatase were uncommon in patients with pediatric liver tumors. Metastatic liver tumors compared with primary malignant liver tumors showed hypo-echogenicity in abdominal ultrasound (US) exam and a lesser presence of vessel invasion and contrast enhancement in computed tomography studies (P < 0.01). CONCLUSIONS It is important to diagnose primary malignant liver tumors before their clinical symptoms and signs develop. Children with chronic hepatitis B virus infection must be followed every 6 months by serum aphal-fetoprotein and abdominal US even when their liver function tests are normal. Image studies with abdominal US and computed tomography scan can differentiate between primary and metastatic liver tumors.
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Affiliation(s)
- Jiaan-Der Wang
- Department of Pediatrics, Taichung Veterans General Hospital, Taichung, Taiwan.
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43
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Milla SS, Lee EY, Buonomo C, Bramson RT. Ultrasound Evaluation of Pediatric Abdominal Masses. ACTA ACUST UNITED AC 2007. [DOI: 10.1016/j.cult.2007.08.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
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Stringer MD. The role of liver transplantation in the management of paediatric liver tumours. Ann R Coll Surg Engl 2007; 89:12-21. [PMID: 17316514 PMCID: PMC1963524 DOI: 10.1308/003588407x155527] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
In recent years, considerable progress has been made in the treatment of children with hepatoblastoma largely due to effective pre-operative chemotherapy. Total hepatectomy and liver transplantation has emerged as an effective treatment for the small proportion of children with unresectable hepatoblastoma limited to the liver. A 5-year survival of 70% can be achieved in such cases. In contrast, the results of liver transplantation in children with hepatocellular cancer remain poor because these tumours are usually advanced with evidence of major vascular invasion and/or extrahepatic spread at the time of presentation. An exception is those children in whom the hepatocellular carcinoma is detected during surveillance of chronic liver disease - they typically have smaller tumours and frequently have a good prognosis after liver transplantation. The role of liver transplantation in children with other primary hepatic malignancies remains uncertain because experience is very limited. Liver transplantation is rarely needed in the management of children with benign liver tumours but, if other treatments have failed, it can be a life-saving intervention.
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Affiliation(s)
- Mark D Stringer
- Children's Liver & GI Unit, St James's University Hospital, Leeds, UK.
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45
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Ozçay F, Canan O, Bilezikçi B, Torgay A, Karakayali H, Haberal M. Effect of living donor liver transplantation on outcome of children with inherited liver disease and hepatocellular carcinoma. Clin Transplant 2007; 20:776-82. [PMID: 17100729 DOI: 10.1111/j.1399-0012.2006.00571.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
We described six children with heritable liver disease and hepatocellular carcinoma treated with living-related liver transplantation. Underlying liver diseases were type-1 tyrosinemia (three patients), progressive familial intrahepatic cholestasis type II (two patients), and Wilson's disease (one patient). Two of the tumors were found incidentally during liver transplantation. Number of nodules was 12, 15, 3, 2, and 1 (in two patients). Three patients were treated with chemotherapy before the procedure. Chemotherapy was not given to any patient after liver transplantation. The mean follow-up was 17.7 +/- 6 months (range: 7-24). All patients are tumor recurrence free. Both graft and patient survival rates are 100% at a median of 18.5 months follow-up. Physicians in charge of treating children with heritable liver disease should screen them periodically for the development of hepatocellular carcinoma. Liver transplantation may offer these children better survival rates.
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Affiliation(s)
- Figen Ozçay
- Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Baskent University Faculty of Medicine, Ankara, Turkey.
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46
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Liver transplantation for hepatocellular carcinoma in children. Curr Opin Organ Transplant 2006. [DOI: 10.1097/01.mot.0000244644.70222.80] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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47
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Arikan C, Kilic M, Nart D, Ozgenc F, Ozkan T, Tokat Y, Yagci RV, Aydogdu S. Hepatocellular carcinoma in children and effect of living-donor liver transplantation on outcome. Pediatr Transplant 2006; 10:42-7. [PMID: 16499586 DOI: 10.1111/j.1399-3046.2005.00395.x] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Hepatocellular carcinoma (HCC) is primarily observed in the older children and in most cases it develops in association with liver cirrhosis. Liver transplantation offers a good chance for long-term cure. To evaluate the outcome of children with HCC and the impact of living-donor orthotopic liver transplantation (OLT) on survival a retrospective review of radiographic, laboratory, pathologic, and therapeutic data in 13 children (six female and seven male) with chronic liver disease accompanied with HCC were studied. The patients were divided into two groups according to therapeutic modality: transplanted and non-transplanted patients. Kaplan-Meier survival curves in various therapeutic groups were plotted. The mean age of patients was 6.4 +/- 4.8 yr. Pediatric end-stage liver disease score was adapted to model for end-stage liver disease score for HCC and ranged between 1-44 and 18-44, respectively. The underlying liver diseases were tyrosinemia type 1 (n = 6), chronic hepatitis B infection (n = 6), glycogen storage disease type 1 (n = 1). Alfa-feto protein levels were elevated in all patients except one. Median number of tumor nodules was three (1-10), median maximal diameter of tumor nodules was 3.4 cm (0.5-8). Eleven patients were eligible for OLT whereas two patients were not eligible. Seven of the 11 patients considered for transplantation underwent living-donor OLT. Remaining four patients died while waiting on cadaveric transplant list. Overall 1 and 4-yr survival rates for all patients were 53.3 and 26.6%, respectively, and were found significantly higher in transplanted children than non-transplanted children (72%, 72% vs. 33% and 16.6%). No patient had tumor recurrence at median of 36-month follow-up after OLT. OLT is a life-saving procedure for children with chronic liver disease accompanying with HCC. Living-donor OLT avoids the risk of tumor progression and transplant ineligibility in these children.
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Affiliation(s)
- C Arikan
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Ege University School of Medicine, Izmir, Turkey.
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48
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Affiliation(s)
- M Beth McCarville
- Department of Radiological Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA
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49
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Yu SB, Kim HY, Eo H, Won JK, Jung SE, Park KW, Kim WK. Clinical Characteristics and Prognosis of Pediatric Hepatocellular Carcinoma. World J Surg 2005; 30:43-50. [PMID: 16369702 DOI: 10.1007/s00268-005-7965-z] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
INTRODUCTION Hepatocellular carcinoma (HCC) is a rare pediatric malignancy that is usually advanced at diagnosis, with a relatively poor prognosis. Extensive treatment, including complete tumor resection, is believed to be necessary for cure. This study was performed to analyze treatment results and to search for prognostic factors of pediatric HCC. METHODS Between March 1982 and February 2004 a total of 16 children had been diagnosed as having HCC in our institution, and a retrospective analysis was performed. RESULTS The median age at diagnosis was 10.5 years, and the male/female ratio was 11:5. As a predisposing condition, hepatitis B virus (HBV) infections were present in 11 (68.8%) and liver cirrhosis in 8 (50.0%). Including 1 patient with a liver transplant, 4 patients (25.0%) underwent a primary operation with complete tumor resection, and 11 (68.8%) received neoadjuvant chemotherapy because of their inoperable state at diagnosis. After neoadjuvant chemotherapy, complete tumor resection was performed in four (36.4%). Thus complete resection was undertaken in a total of eight patients (50.0%). The estimated 5-year survival rate of all patients was 27.3%. The 5-year survival rate for patients who underwent complete tumor resection was 62.5%, and for those who underwent palliative resection or no operation it was 0%. The statistically significant prognostic factors were tumor stage, presence of metastasis, and complete tumor resection. CONCLUSIONS This study confirmed that complete tumor resection is essential for cure in pediatric patients with HCC, and neoadjuvant chemotherapy improves the tumors' resectability.
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Affiliation(s)
- Seung-Beom Yu
- Department of Surgery, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul , 110-744, Korea
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50
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Richter A, Grabhorn E, Schulz A, Schaefer HJ, Burdelski M, Ganschow R. Hepatoblastoma in a child with progressive familial intrahepatic cholestasis. Pediatr Transplant 2005; 9:805-8. [PMID: 16269056 DOI: 10.1111/j.1399-3046.2005.00380.x] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
End-stage liver cirrhosis because of metabolic or infectious diseases predisposes to hepatic malignancies like hepatocellular carcinoma. We report the first case of hepatoblastoma incidentally detected in the explanted liver of a 2-yr-old child undergoing liver transplantation for cirrhosis because of progressive familial intrahepatic cholestasis (PFIC). The diagnosis was difficult to obtain. The hepatoblastoma was not seen on ultrasound examination of the cirrhotic liver. As we could confirm retrospectively, alpha fetoprotein (AFP) was found elevated prior to transplantation. Two years after successful transplantation, there are no signs of malignancy detectable by clinical and radiological methods. We conclude from this case that PFIC may induce hepatoblastoma and that children with liver cirrhosis should undergo routine screening of serum AFP concentration.
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Affiliation(s)
- A Richter
- Department of Pediatrics, Hamburg School of Medicine, University of Hamburg, Germany.
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