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Zhang H, Pan X, Wu Q, Wu Y, Zheng N, Ning S, Zeng D, Chen L, Li W, Wang J, Jiang T, Long X, Watabe H, Wu H, Wu Y, Wei Y, Yin X. Synthesis and characterization of functional chitosan-based microspheres as biodegradable yttrium-90 delivery system for radioembolization therapy. Int J Biol Macromol 2025; 312:144090. [PMID: 40360115 DOI: 10.1016/j.ijbiomac.2025.144090] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2024] [Revised: 01/02/2025] [Accepted: 05/08/2025] [Indexed: 05/15/2025]
Abstract
Transarterial radioembolization (TARE) using yttrium-90 (90Y)-labeled glass and resin microspheres is an emerging therapeutic technique for hepatocellular carcinoma (HCC). However, the non-biodegradability and rapid settlement of current commercial microspheres might hinder their even distribution and repetitive administration thus causing unsatisfactory therapeutic effects. In this context, novel functional chitosan-based microspheres (CPIs) that can efficiently label Y as a favorable TARE material were developed for the first time by successive grafting poly (glycidyl methacrylate) (PGMA) and iminodiacetic acid (IDA) onto chitosan microspheres (CMs). The results confirmed that the CPIs had desirable spherical shapes with average diameters of around 20.9 μm, an ideal settlement rate within 5 min, and considerable biodegradability at 10th weeks. It reached Y adsorption equilibrium within 30 min and maintained the maximum adsorption capacity up to 14.95 mg g-1 at pH 6.0 following pseudo-second-order kinetic and Langmuir models. Additionally, Y-labeled CPIs were rather stable in vitro, for which Y would firmly interact with the sodium carboxylate group and tertiary amine nitrogen atoms on IDA, and its leakage when shaken in phosphate-buffered saline for 24 h was barely detected. Altogether, these properties of the as-developed CPIs hold great potential as promising radioembolization microspheres for TARE therapy against liver cancer.
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Affiliation(s)
- Haoyu Zhang
- School of Nuclear Science and Technology, University of South China, 28 Changsheng West Road, Hengyang 421001, China
| | - Xiangni Pan
- School of Nuclear Science and Technology, University of South China, 28 Changsheng West Road, Hengyang 421001, China
| | - Qiang Wu
- School of Nuclear Science and Technology, University of South China, 28 Changsheng West Road, Hengyang 421001, China
| | - Yehuizi Wu
- School of Nuclear Science and Technology, University of South China, 28 Changsheng West Road, Hengyang 421001, China
| | - Ningchao Zheng
- School of Nuclear Science and Technology, University of South China, 28 Changsheng West Road, Hengyang 421001, China
| | - Shunyan Ning
- School of Nuclear Science and Technology, University of South China, 28 Changsheng West Road, Hengyang 421001, China
| | - Deqian Zeng
- School of Nuclear Science and Technology, University of South China, 28 Changsheng West Road, Hengyang 421001, China
| | - Lifeng Chen
- School of Nuclear Science and Technology, University of South China, 28 Changsheng West Road, Hengyang 421001, China
| | - Wenlong Li
- School of Nuclear Science and Technology, University of South China, 28 Changsheng West Road, Hengyang 421001, China
| | - Ji Wang
- School of Nuclear Science and Technology, University of South China, 28 Changsheng West Road, Hengyang 421001, China
| | - Tianjiao Jiang
- School of Nuclear Science and Technology, University of South China, 28 Changsheng West Road, Hengyang 421001, China
| | - Xizhi Long
- Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang 421001, China
| | - Hiroshi Watabe
- Division of Radiation Protection and Safety Control, Cyclotron and Radioisotope Center, Tohoku University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai, Miyagi 980-8578, Japan
| | - Hao Wu
- School of Nuclear Science and Engineering, Shanghai Jiao Tong University, 800 Dong Chuan Road, Shanghai 200240, China
| | - Yan Wu
- School of Nuclear Science and Engineering, Shanghai Jiao Tong University, 800 Dong Chuan Road, Shanghai 200240, China
| | - Yuezhou Wei
- School of Nuclear Science and Technology, University of South China, 28 Changsheng West Road, Hengyang 421001, China; School of Nuclear Science and Engineering, Shanghai Jiao Tong University, 800 Dong Chuan Road, Shanghai 200240, China
| | - Xiangbiao Yin
- School of Nuclear Science and Technology, University of South China, 28 Changsheng West Road, Hengyang 421001, China; Key Laboratory of Advanced Nuclear Energy Design and Safety, Ministry of Education, University of South China, 28 Changsheng West Road, Hengyang, China.
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Ziyaee F, Dehghani SM, Forooghi M, Bahador A, Foroutan H, Nikoupour H, Geramizadeh B, Haghighat M, Imanieh MH, Honar N, Shahramian I, Ataollahi M, Ansary N, Ghasemian M, Rouhafshari M, Radaei Z, Shahrebabaki MM, Khatouni MS. Hepatic tumors in Iranian children: Characteristics and survival predictors. Pediatr Neonatol 2025:S1875-9572(25)00064-6. [PMID: 40246679 DOI: 10.1016/j.pedneo.2024.10.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Revised: 10/01/2024] [Accepted: 10/14/2024] [Indexed: 04/19/2025] Open
Abstract
BACKGROUND Hepatic tumors are rare in children. This study was conducted to determine the characteristics of liver masses in children and identify the independent predictors of their survival. METHODS Medical records of children aged <18 years with a confirmed diagnosis of hepatic tumor diagnosed between January 2008 and December 2023 at two referral centers affiliated to Shiraz University of Medical Sciences, southern Iran, were reviewed. RESULTS There were 153 children with hepatic tumors. The median age of the patients was 2 (IQR, 1-5) years. Abdominal pain and distension, and presence of a palpable mass and fever were the most common signs and symptoms at presentation. The most common tumor was hepatoblastoma (64.5 %) followed by hepatocellular carcinoma (HCC, 9.9 %). Right hepatectomy and hepatic segmentectomy were the most common surgical approach used. Children with hepatoblastoma were significantly (p < 0.001) younger than those with HCC. The risk of hepatoblastoma in males was twice that in females. Jaundice was not common in those with hepatoblastoma but it was in HCC. About a quarter of patients died. After adjusting for covariates, abdominal pain (adj OR = 4.90) and distension (adj OR = 3.17), and a diagnosis of HCC (adj OR = 13.63) were independent predictors of a poor prognosis. CONCLUSIONS The characteristics of pediatric hepatic tumors in our study were similar to those reported in most studies. Abdominal pain and distension and presence of HCC or jaundice were independent predictors of a poor prognosis.
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Affiliation(s)
- Fateme Ziyaee
- Department of Pediatric Gastroenterology, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Seyed Mohsen Dehghani
- Department of Pediatric Gastroenterology, Shiraz University of Medical Sciences, Shiraz, Iran; Shiraz Transplant Center, Abu-Ali Sina Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mehdi Forooghi
- Department of Pediatric Surgery, Shiraz University of Medical Sciences, Shiraz, Iran.
| | - Ali Bahador
- Shiraz Transplant Center, Abu-Ali Sina Hospital, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Pediatric Surgery, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Hamidreza Foroutan
- Department of Pediatric Surgery, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Hamed Nikoupour
- Shiraz Transplant Center, Abu-Ali Sina Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Bita Geramizadeh
- Shiraz Transplant Center, Abu-Ali Sina Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mahmood Haghighat
- Department of Pediatric Gastroenterology, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mohammad Hadi Imanieh
- Department of Pediatric Gastroenterology, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Naser Honar
- Department of Pediatric Gastroenterology, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Iraj Shahramian
- Department of Pediatric Gastroenterology, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Maryam Ataollahi
- Department of Pediatric Gastroenterology, Shiraz University of Medical Sciences, Shiraz, Iran; Shiraz Transplant Center, Abu-Ali Sina Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Narges Ansary
- Department of Pediatric Gastroenterology, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mehdi Ghasemian
- , School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mahsa Rouhafshari
- Department of Pediatric Gastroenterology, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Zahra Radaei
- Department of Pediatric Gastroenterology, Shiraz University of Medical Sciences, Shiraz, Iran
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Ro E, Schooler GR, Morin CE, Khanna G, Towbin AJ. Update on the imaging evaluation of pediatric liver tumors from the ACR Pediatric LI-RADS Working Group. Abdom Radiol (NY) 2025; 50:1171-1179. [PMID: 39292279 DOI: 10.1007/s00261-024-04565-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2024] [Revised: 08/29/2024] [Accepted: 08/30/2024] [Indexed: 09/19/2024]
Affiliation(s)
- Esther Ro
- Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, USA.
- Northwestern University Feinberg School of Medicine, Chicago, USA.
| | - Gary R Schooler
- Cincinnati Children's Hospital, Cincinnati, USA
- University of Cincinnati College of Medicine, Cincinnati, USA
| | - Cara E Morin
- Cincinnati Children's Hospital, Cincinnati, USA
- University of Cincinnati College of Medicine, Cincinnati, USA
| | - Geetika Khanna
- Emory University and Children's Healthcare of Atlanta, Atlanta, USA
| | - Alexander J Towbin
- Cincinnati Children's Hospital, Cincinnati, USA
- University of Cincinnati College of Medicine, Cincinnati, USA
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Medio P, Matesanz S, Margareto M, Ostos P, Palomo C, Hernández Oliveros F, Moreno AA. Outcomes of Pediatric Hepatocellular Carcinoma: A Single-Center Experience With Resection Versus Transplantation. Pediatr Transplant 2024; 28:e14882. [PMID: 39523995 DOI: 10.1111/petr.14882] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Revised: 09/05/2024] [Accepted: 10/13/2024] [Indexed: 11/16/2024]
Abstract
BACKGROUND Pediatric hepatocellular carcinoma (HCC) presents significant challenges due to its aggressive nature, with survival depending on complete resection. We aimed to assess outcomes between liver resection (LR) and liver transplantation (LT). METHODS A total of 25 patients were retrieved, four of whom were classified as palliative at diagnosis. A subanalysis comparing cirrhotic liver (n = 14) versus de novo (n = 11) HCC was performed to identify confounding variables. Further evaluation focused on the 21 children with histologically confirmed HCC who underwent LR (n = 7) versus LT (n = 14). Kaplan-Meier survival curves were constructed. RESULTS The mean age was 7.8 ± 6.1 years for patients with cirrhotic liver and 12.1 ± 3.5 years for de novo HCC. Our group observed overall total survival rates of 100%, 85%, and 77% at 12, 36, and 60 months, respectively. De novo tumors had a higher recurrence rate and a poorer prognosis (p = 0.039 and p = 0.045). The disease-free survival at 60 months in our cohort was significantly lower among the LR group compared to the LT group (14% vs. 82%; p = 0.0081). Recurrence after initial management (n = 8) showed location differences between LR and LT. Preoperative alpha-fetoprotein (AFP) was elevated in 71% of children, but did not correlate with recurrence or compromised survival. Elevated AFP 3 months post-operation affected the course negatively (p = 0.044). Tumor number and diameter exhibited a trend towards poorer outcomes. CONCLUSIONS These findings emphasize the need for comprehensive pediatric surgical guidelines for HCC. We recommend LT over LR in pediatric cases. Extrahepatic disease post-neoadjuvant chemotherapy remains the only absolute contraindication.
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Affiliation(s)
- Paula Medio
- Faculty of Medicine, Autonomous University of Madrid, Madrid, Spain
| | - Sofía Matesanz
- Faculty of Medicine, Autonomous University of Madrid, Madrid, Spain
| | - María Margareto
- Faculty of Medicine, Autonomous University of Madrid, Madrid, Spain
| | - Paula Ostos
- Faculty of Medicine, Autonomous University of Madrid, Madrid, Spain
| | - Claudia Palomo
- Faculty of Medicine, Autonomous University of Madrid, Madrid, Spain
| | - Francisco Hernández Oliveros
- Division of Abdominal Organ Transplantation and Hepatobiliary Surgery, Department of Pediatric Surgery, La Paz University Hospital, Madrid, Spain
| | - Ane Andrés Moreno
- Division of Abdominal Organ Transplantation and Hepatobiliary Surgery, Department of Pediatric Surgery, La Paz University Hospital, Madrid, Spain
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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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Stefanowicz M, Kaliciński P, Ismail H, Kowalski A, Broniszczak D, Szymczak M, Pankowska-Woźniak K, Roszkiewicz A, Święszkowska E, Kamińska D, Szymańska S, Kowalewski G. Risk for Recurrence in Long-Term Follow-Up of Children after Liver Transplantation for Hepatoblastoma or Hepatocellular Carcinoma. CHILDREN (BASEL, SWITZERLAND) 2024; 11:193. [PMID: 38397305 PMCID: PMC10887907 DOI: 10.3390/children11020193] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Revised: 01/28/2024] [Accepted: 01/30/2024] [Indexed: 02/25/2024]
Abstract
The aim of this study was to assess the long-term results of liver transplantation (LT) in pediatric patients with unresectable hepatoblastoma (HB) or hepatocellular carcinoma (HCC) with special reference to the risk of tumor recurrence. We retrospectively analyzed data from 46 HB and 26 HCC patients who underwent LT between 1990 and 2022. In HCC patients, we compared outcomes depending on donor type. We evaluated the impact of a number of risk factors on recurrence-free survival after LT. Estimated patient survival after 5, 10, and 15 years was 82%, 73%, and 73% in the HB group and 79%, 75%, and 75% in the HCC group, respectively (p = 0.76). In the HCC group, living donor LT (LDLT) and deceased donor LT (DDLT) provided similar patient survival (p = 0.09). Estimated recurrence-free survival in patients who had three or fewer risk factors was significantly better than in patients with more than three risk factors (p = 0.0001). Adequate patient selection is necessary when considering LT for primary liver tumors in children. The presence of more than three risk factors is associated with a very high risk of recurrence and indicates poor prognosis, whereas extrahepatic disease may be considered a contraindication for transplantation.
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Affiliation(s)
- Marek Stefanowicz
- Department of Pediatric Surgery and Organ Transplantation, The Children’s Memorial Health Institute, 04-730 Warsaw, Poland; (M.S.); (H.I.); (A.K.); (D.B.); (M.S.); (K.P.-W.); (A.R.); (G.K.)
| | - Piotr Kaliciński
- Department of Pediatric Surgery and Organ Transplantation, The Children’s Memorial Health Institute, 04-730 Warsaw, Poland; (M.S.); (H.I.); (A.K.); (D.B.); (M.S.); (K.P.-W.); (A.R.); (G.K.)
| | - Hor Ismail
- Department of Pediatric Surgery and Organ Transplantation, The Children’s Memorial Health Institute, 04-730 Warsaw, Poland; (M.S.); (H.I.); (A.K.); (D.B.); (M.S.); (K.P.-W.); (A.R.); (G.K.)
| | - Adam Kowalski
- Department of Pediatric Surgery and Organ Transplantation, The Children’s Memorial Health Institute, 04-730 Warsaw, Poland; (M.S.); (H.I.); (A.K.); (D.B.); (M.S.); (K.P.-W.); (A.R.); (G.K.)
| | - Dorota Broniszczak
- Department of Pediatric Surgery and Organ Transplantation, The Children’s Memorial Health Institute, 04-730 Warsaw, Poland; (M.S.); (H.I.); (A.K.); (D.B.); (M.S.); (K.P.-W.); (A.R.); (G.K.)
| | - Marek Szymczak
- Department of Pediatric Surgery and Organ Transplantation, The Children’s Memorial Health Institute, 04-730 Warsaw, Poland; (M.S.); (H.I.); (A.K.); (D.B.); (M.S.); (K.P.-W.); (A.R.); (G.K.)
| | - Katarzyna Pankowska-Woźniak
- Department of Pediatric Surgery and Organ Transplantation, The Children’s Memorial Health Institute, 04-730 Warsaw, Poland; (M.S.); (H.I.); (A.K.); (D.B.); (M.S.); (K.P.-W.); (A.R.); (G.K.)
| | - Anna Roszkiewicz
- Department of Pediatric Surgery and Organ Transplantation, The Children’s Memorial Health Institute, 04-730 Warsaw, Poland; (M.S.); (H.I.); (A.K.); (D.B.); (M.S.); (K.P.-W.); (A.R.); (G.K.)
| | - Ewa Święszkowska
- Department of Oncology, The Children’s Memorial Health Institute, 04-730 Warsaw, Poland;
| | - Diana Kamińska
- Department of Gastroenterology, Hepatology, Nutritional Disorders and Pediatrics, The Children’s Memorial Health Institute, 04-730 Warsaw, Poland;
| | - Sylwia Szymańska
- Department of Pathomorphology, The Children’s Memorial Health Institute, 04-730 Warsaw, Poland;
| | - Grzegorz Kowalewski
- Department of Pediatric Surgery and Organ Transplantation, The Children’s Memorial Health Institute, 04-730 Warsaw, Poland; (M.S.); (H.I.); (A.K.); (D.B.); (M.S.); (K.P.-W.); (A.R.); (G.K.)
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Dong Y, Cekuolis A, Schreiber-Dietrich D, Augustiniene R, Schwarz S, Möller K, Nourkami-Tutdibi N, Chen S, Cao JY, Huang YL, Wang Y, Taut H, Grevelding L, Dietrich CF. Review on Pediatric Malignant Focal Liver Lesions with Imaging Evaluation: Part I. Diagnostics (Basel) 2023; 13:3568. [PMID: 38066809 PMCID: PMC10706220 DOI: 10.3390/diagnostics13233568] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2023] [Revised: 11/13/2023] [Accepted: 11/27/2023] [Indexed: 01/09/2024] Open
Abstract
Malignant focal liver lesions (FLLs) are commonly reported in adults but rarely seen in the pediatric population. Due to the rarity, the understanding of these diseases is still very limited. In children, most malignant FLLs are congenital. It is very important to choose appropriate imaging examination concerning various factors. This paper will outline common pediatric malignant FLLs, including hepatoblastoma, hepatocellular carcinoma, and cholangiocarcinoma and discuss them against the background of the latest knowledge on comparable/similar tumors in adults. Medical imaging features are of vital importance for the non-invasive diagnosis and follow-up of treatment of FLLs in pediatric patients. The use of CEUS in pediatric patients for characterizing those FLLs that remain indeterminate on conventional B mode ultrasounds may be an effective option in the future and has great potential to be integrated into imaging algorithms without the risk of exposure to ionizing radiation.
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Affiliation(s)
- Yi Dong
- Department of Ultrasound, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China; (Y.D.); (S.C.); (J.-Y.C.); (Y.-L.H.); (Y.W.)
| | - Andrius Cekuolis
- Ultrasound Section, Department of Pediatric Radiology, Radiology and Nuclear Medicine Centre, Vilnius University Hospital Santaros Klinikos, 08661 Vilnius, Lithuania; (A.C.); (R.A.)
| | | | - Rasa Augustiniene
- Ultrasound Section, Department of Pediatric Radiology, Radiology and Nuclear Medicine Centre, Vilnius University Hospital Santaros Klinikos, 08661 Vilnius, Lithuania; (A.C.); (R.A.)
| | - Simone Schwarz
- Department of Neonatology and Pediatric Intensive Care Medicine, Sana Kliniken Duisburg GmbH, 47055 Duisburg, Germany;
| | - Kathleen Möller
- Medical Department I/Gastroenterology, SANA Hospital Lichtenberg, 10365 Berlin, Germany;
| | - Nasenien Nourkami-Tutdibi
- Saarland University Medical Center, Hospital of General Pediatrics and Neonatology, 66421 Homburg, Germany;
| | - Sheng Chen
- Department of Ultrasound, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China; (Y.D.); (S.C.); (J.-Y.C.); (Y.-L.H.); (Y.W.)
| | - Jia-Ying Cao
- Department of Ultrasound, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China; (Y.D.); (S.C.); (J.-Y.C.); (Y.-L.H.); (Y.W.)
| | - Yun-Lin Huang
- Department of Ultrasound, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China; (Y.D.); (S.C.); (J.-Y.C.); (Y.-L.H.); (Y.W.)
| | - Ying Wang
- Department of Ultrasound, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China; (Y.D.); (S.C.); (J.-Y.C.); (Y.-L.H.); (Y.W.)
| | - Heike Taut
- Children’s Hospital, Universitätsklinikum Dresden, Technische Universität Dresden, 01069 Dresden, Germany;
| | - Lara Grevelding
- Department of Pediatrics, Division of Pneumology, Allergology, Infectious Diseases and Gastroenterology, University Hospital Frankfurt, Goethe University, 60323 Frankfurt, Germany
| | - Christoph F. Dietrich
- Department Allgemeine Innere Medizin (DAIM), Kliniken Hirslanden Beau Site, Salem und Permanence, 3013 Bern, Switzerland
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Vij M, Menon J, Subbiah K, Raju LP, Gowrisankar G, Shanmugum N, Kaliamoorthy I, Rammohan A, Rela M. Pathologic and Immunophenotypic Characterization of Syncytial Giant Cell Variant of Pediatric Hepatocellular Carcinoma. A Distinct Subtype. Fetal Pediatr Pathol 2023; 42:709-718. [PMID: 37071763 DOI: 10.1080/15513815.2023.2201318] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Revised: 04/01/2023] [Accepted: 04/04/2023] [Indexed: 04/20/2023]
Abstract
INTRODUCTION Hepatocellular carcinoma (HCC) in pediatrics has a uniformly poor prognosis. Complete surgical resection or liver transplantation remain the only curative options. In contrast to adult HCC, literature on pediatric HCC is sparse and a majority of the distinct subtypes are undefined with regards to their histology, immunohistochemistry and prognosis. CASE REPORT Two infants, one with biliary atresia and another with transaldolase deficiency, underwent living donor liver transplants. Explant-liver histopathology revealed tumor with diffuse neoplastic syncytial giant cell pattern. Immunophenotypic characterization highlighted expression of epithelial cell adhesion molecule, alpha fetoprotein and metallothionein. CONCLUSION HCC with syncytial giant cells variant can occur in infants with underlying liver disease, specifically in our experience, with biliary atresia and another with transaldolase deficiency.
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Affiliation(s)
- Mukul Vij
- Department of Pathology, Dr. Rela Institute & Medical Centre, Chennai, Tamil Nadu, India
| | - Jagadeesh Menon
- The Institute of Liver Disease & Transplantation, Dr. Rela Institute & Medical Centre, Chennai, Tamil Nadu, India
| | - Komalavalli Subbiah
- The Institute of Liver Disease & Transplantation, Dr. Rela Institute & Medical Centre, Chennai, Tamil Nadu, India
| | - Lexmi Priya Raju
- Department of Pathology, Dr. Rela Institute & Medical Centre, Chennai, Tamil Nadu, India
| | - Gowripriya Gowrisankar
- Department of Pathology, Dr. Rela Institute & Medical Centre, Chennai, Tamil Nadu, India
| | - Naresh Shanmugum
- The Institute of Liver Disease & Transplantation, Dr. Rela Institute & Medical Centre, Chennai, Tamil Nadu, India
| | - Ilankumaran Kaliamoorthy
- The Institute of Liver Disease & Transplantation, Dr. Rela Institute & Medical Centre, Chennai, Tamil Nadu, India
| | - Ashwin Rammohan
- The Institute of Liver Disease & Transplantation, Dr. Rela Institute & Medical Centre, Chennai, Tamil Nadu, India
| | - Mohamed Rela
- The Institute of Liver Disease & Transplantation, Dr. Rela Institute & Medical Centre, Chennai, Tamil Nadu, India
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Long-Term Outcome Following Liver Transplantation for Primary Hepatic Tumors-A Single Centre Observational Study over 40 Years. CHILDREN (BASEL, SWITZERLAND) 2023; 10:children10020202. [PMID: 36832331 PMCID: PMC9954409 DOI: 10.3390/children10020202] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Revised: 01/11/2023] [Accepted: 01/17/2023] [Indexed: 01/24/2023]
Abstract
The incidence of pediatric liver tumors in general has been rising over the last years and so is the number of children undergoing liver transplantation for this indication. To contribute to the ongoing improvement of pre- and post-transplant care, we aim to describe outcome and risk factors in our patient cohort. We have compared characteristics and outcome for patients transplanted for hepatoblastoma to other liver malignancies in our center between 1983 and 2022 and analysed influential factors on tumor recurrence and mortality using nominal logistic regression analysis. Of 39 children (16 f) who had transplants for liver malignancy, 31 were diagnosed with hepatoblastoma. The proportion of malignant tumors in the transplant cohort rose from 1.9% (1983-1992) to 9.1% in the current decade (p < 0.0001). Hepatoblastoma patients were transplanted at a younger age and were more likely to have tumor extent beyond the liver. Post-transplant bile flow impairment requiring intervention was significantly higher compared to our total cohort (48 vs. 24%, p > 0.0001). Hearing loss was a common side effect of ototoxic chemotherapy in hepatoblastoma patients (48%). The most common maintenance immunosuppression were mTor-inhibitors. Risk factors for tumor recurrence in patients with hepatoblastoma were higher AFP before transplant (AFPpre-LTX), a low ratio of AFPmax to AFPpre-LTX and salvage transplantation. Liver malignancies represent a rising number of indications for liver transplantation in childhood. Primary tumor resection can spare a liver transplant with all its long-term complications, but in case of tumor recurrence, transplantation might have inferior outcome. The rate of acute biopsy-proven rejections and biliary complications in comparison to our total transplant cohort needs further investigations.
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10
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Grimaldi C, de Ville de Goyet J, Bici K, Cianci MC, Callea F, Morabito A. The role of liver transplantation in the care of primary hepatic vascular tumours in children. Front Oncol 2022; 12:1026232. [PMID: 36505841 PMCID: PMC9730342 DOI: 10.3389/fonc.2022.1026232] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Accepted: 10/31/2022] [Indexed: 11/25/2022] Open
Abstract
Liver transplantation (LT) is the standard of care for many liver conditions, such as end-stage liver diseases, inherited metabolic disorders, and primary liver malignancies. In the latter group, indications of LT for hepatoblastoma and hepatocellular carcinoma evolved and are currently available for many non-resectable cases. However, selection criteria apply, as the absence of active metastases. Evidence of good long-term outcomes has validated the LT approach for managing these malignancies in the context of specialist and multidisciplinary approach. Nevertheless, LT's role in treating primary vascular tumours of the liver in children, both benign and malignant, remains somewhat controversial. The rarity of the different diseases and the heterogeneity of pathological definitions contribute to the controversy and make evaluating the benefit/risk ratio and outcomes quite difficult. In this narrative review, we give an overview of primary vascular tumours of the liver in children, the possible indications and the outcomes of LT.
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Affiliation(s)
- Chiara Grimaldi
- Department of Pediatric Surgery, Meyer Children’s Hospital, University of Florence, Florence, Italy,*Correspondence: Chiara Grimaldi,
| | - Jean de Ville de Goyet
- Department of Pediatrics, IRCCS-Istituto Mediterraneo per i Trapianti e Terapie ad altra specializzazione (ISMETT) (Institute for Scientific-Based Care and Research-Mediterranean Institute for Transplantation and Advanced Specialized Therapies), Palermo, Italy
| | - Kejd Bici
- Department of Pediatric Surgery, Meyer Children’s Hospital, University of Florence, Florence, Italy
| | - Maria Chiara Cianci
- Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Florence, Italy
| | - Francesco Callea
- Department of Histopathology, Bugando Medical Centre, Catholic University of Healthy Allied Sciences, Mwanza, Tanzania
| | - Antonino Morabito
- Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Florence, Italy
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11
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Baumann U, Karam V, Adam R, Fondevila C, Dhawan A, Sokal E, Jacquemin E, Kelly DA, Grabhorn E, Pawlowska J, D'Antiga L, Jara Vega P, Debray D, Polak WG, de Ville de Goyet J, Verkade HJ. Prognosis of Children Undergoing Liver Transplantation: A 30-Year European Study. Pediatrics 2022; 150:189501. [PMID: 36111446 DOI: 10.1542/peds.2022-057424] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/14/2022] [Indexed: 01/17/2023] Open
Abstract
OBJECTIVES The European Liver Transplant Registry has been collecting data on virtually all pediatric liver transplant (PLT) procedures in Europe since 1968. We analyzed patient outcome over time and identified parameters associated with long-term patient outcome. METHODS Participating centers and European organ-sharing organizations provided retrospective data to the European Liver Transplant Registry. To identify trends, data were grouped into consecutive time spans: era A: before 2000, era B: 2000 to 2009, and the current era, era C: since 2010. RESULTS From June 1968 until December 2017, 16 641 PLT were performed on 14 515 children by 133 centers. The children <7 years of age represented 58% in era A, and 66% in the current era (P <.01). The main indications for PLT were congenital biliary diseases (44%) and metabolic diseases (18%). Patient survival at 5 years is currently 86% overall and 97% in children who survive the first year after PLT. The survival rate has improved from 74% in era A to 83% in era B and 85% in era C (P <.0001). Low-volume centers (<5 PLT/year) represented 75% of centers but performed only 19% of PLT and were associated with a decreased survival rate. In the current era, however, survival rates has become irrespective of volume. Infection is the leading cause of death (4.1%), followed by primary nonfunction of the graft (1.4%). CONCLUSIONS PLT has become a highly successful medical treatment that should be considered for all children with end-stage liver disease. The main challenge for further improving the prognosis remains the early postoperative period.
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Affiliation(s)
- Ulrich Baumann
- Hannover Medical School, Divisions of Paediatric Gastroenterology and Hepatology, Department for Paediatric Kidney, Liver, and Metabolic Diseases, Hannover, Germany.,Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom.,Liver Unit, Birmingham Women's and Children's Hospital, Birmingham, United Kingdom.,European Liver Transplant Registry, AP-HP Hôpital Paul Brousse, Research Unit "Chronotherapy, cancers and transplantation," University Paris-Saclay, Villejuif, France.,European Liver and Intestine Transplant Association, Padova, Italy.,European Reference Network TransplantChild, La Paz University Hospital, Madrid, Spain
| | - Vincent Karam
- European Liver Transplant Registry, AP-HP Hôpital Paul Brousse, Research Unit "Chronotherapy, cancers and transplantation," University Paris-Saclay, Villejuif, France.,European Liver and Intestine Transplant Association, Padova, Italy
| | - René Adam
- European Liver Transplant Registry, AP-HP Hôpital Paul Brousse, Research Unit "Chronotherapy, cancers and transplantation," University Paris-Saclay, Villejuif, France.,European Liver and Intestine Transplant Association, Padova, Italy
| | - Constantino Fondevila
- European Liver Transplant Registry, AP-HP Hôpital Paul Brousse, Research Unit "Chronotherapy, cancers and transplantation," University Paris-Saclay, Villejuif, France.,Department of General and Digestive Surgery, Hospital Universitario La Paz, IDIPAZ, CIBERehd, Madrid, Spain
| | - Anil Dhawan
- King's College Hospital, London, United Kingdom
| | - Etienne Sokal
- Cliniques Universitaires Saint Luc, Catholic University of Louvain, Brussels, Belgium
| | - Emmanuel Jacquemin
- Pediatric Hepatology and Liver Transplantation Unit, National Reference Centre for Biliary Atresia and Genetic Cholestasis, FILFOIE, ERN RARE LIVER, Bicêtre Hospital, Assistance Publique: Hôpitaux de Paris, University Paris-Saclay, Le Kremlin-Bicêtre; Inserm U1193, Hepatinov, University Paris-Saclay, Orsay, France
| | - Deirdre A Kelly
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom.,Liver Unit, Birmingham Women's and Children's Hospital, Birmingham, United Kingdom
| | - Enke Grabhorn
- European Reference Network TransplantChild, La Paz University Hospital, Madrid, Spain.,Childreńs Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Joanna Pawlowska
- European Reference Network TransplantChild, La Paz University Hospital, Madrid, Spain.,Department of Gastroenterology, Hepatology, Nutritional Disorders and Pediatrics, The Children's Memorial Health Institute, Warsaw, Poland
| | - Lorenzo D'Antiga
- European Reference Network TransplantChild, La Paz University Hospital, Madrid, Spain.,Paediatric Hepatology, Gastroenterology, and Transplantation, Hospital Papa Giovanni XXIII, Bergamo, Italy
| | - Paloma Jara Vega
- European Reference Network TransplantChild, La Paz University Hospital, Madrid, Spain.,Paediatric Hepatology Service, Coordinator ERN TransplantChild, Hospital Infantil Universitario La Paz, Madrid, Spain
| | - Dominique Debray
- European Reference Network TransplantChild, La Paz University Hospital, Madrid, Spain.,Pediatric Liver Unit and Reference Center for Biliary Atresia and Genetic Cholestasis, APHP-Hôpital Necker, Université de Paris, Paris, France
| | - Wojciech G Polak
- European Liver and Intestine Transplant Association, Padova, Italy.,Department of Surgery, Division of Hepatopancreatobiliary and Transplant Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Jean de Ville de Goyet
- Department for the Treatment and Study of Pediatric Abdominal Diseases and Abdominal Transplantation, ISMETT, Palermo, Italy
| | - Henkjan J Verkade
- European Liver and Intestine Transplant Association, Padova, Italy.,Dept. of Pediatrics, Beatrix Children's Hospital/University Medical Center Groningen, University of Groningen, ERN RareLiver, Groningen, The Netherlands
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12
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Boster JM, Superina R, Mazariegos GV, Tiao GM, Roach JP, Lovell MA, Greffe BS, Yanni G, Leung DH, Elisofon SA, McDiarmid SV, Gupta NA, Lobritto SJ, Lemoine C, Stoll JM, Vitola BE, Daniel JF, Sayed BA, Desai DM, Martin AE, Amin A, Anand R, Anderson SG, Sundaram SS. Predictors of survival following liver transplantation for pediatric hepatoblastoma and hepatocellular carcinoma: Experience from the Society of Pediatric Liver Transplantation (SPLIT). Am J Transplant 2022; 22:1396-1408. [PMID: 34990053 DOI: 10.1111/ajt.16945] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2021] [Revised: 12/28/2021] [Accepted: 12/28/2021] [Indexed: 01/25/2023]
Abstract
Management of unresectable pediatric hepatoblastoma (HB) and hepatocellular carcinoma (HCC) remains challenging. The Society of Pediatric Liver Transplantation (SPLIT) database was used to study survival predictors in pediatric liver transplantation (LT) for HB and HCC. Event-free survival (EFS), associated risk factors, and postoperative complications were studied in children requiring LT for HB/HCC at 16 SPLIT centers. Three-year EFS was 81% for HB (n = 157) and 62% for HCC (n = 18) transplants. Of HB transplants, 6.9% were PRETEXT II and 15.3% were POST-TEXT I/II. Tumor extent did not impact survival (p = NS). Salvage (n = 13) and primary HB transplants had similar 3-year EFS (62% versus 78%, p = NS). Among HCC transplants, 3-year EFS was poorer in older patients (38% in ≥8-year-olds vs 86% <8-year-olds) and those with larger tumors (48% for those beyond versus 83% within Milan criteria, p = NS). Risk of infection (HR 1.5, 95% CI 1.1-2.2, p = .02) and renal injury (HR 2.4, 95% CI 1.7-3.3, p < .001) were higher in malignant versus nonmalignant LT. Survival is favorable for pediatric HB and HCC LT, including outcomes after salvage transplant. Unexpected numbers of LTs occurred in PRE/POST-TEXT I/II tumors. Judicious patient selection is critical to distinguish tumors that are potentially resectable; simultaneously, we must advocate for patients with unresectable malignancies to receive organs.
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Affiliation(s)
- Julia M Boster
- Department of Pediatrics, Children's Hospital Colorado and University of Colorado, Aurora, Colorado, USA
| | - Riccardo Superina
- Department of Surgery, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA
| | - George V Mazariegos
- Department of Surgery, University of Pittsburgh Medical Center Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Gregory M Tiao
- Department of Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
| | - Jonathan P Roach
- Department of Surgery, Children's Hospital Colorado and University of Colorado, Aurora, Colorado, USA
| | - Mark A Lovell
- Department of Pathology, Children's Hospital Colorado and University of Colorado, Aurora, Colorado, USA
| | - Brian S Greffe
- Department of Pediatric Oncology, Children's Hospital Colorado and University of Colorado, Aurora, Colorado, USA
| | - George Yanni
- Department of Pediatrics, Children's Hospital Los Angeles, Los Angeles, California, USA
| | - Daniel H Leung
- Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas, USA
| | - Scott A Elisofon
- Department of Pediatrics, Boston Children's Hospital, Massachusetts, USA
| | - Suzanne V McDiarmid
- Department of Pediatrics, University of California and Los Angeles Mattel Children's Hospital, Los Angeles, California, USA
| | - Nitika A Gupta
- Department of Pediatrics, Children's Healthcare of Atlanta and Emory University School of Medicine, Atlanta, Georgia, USA
| | - Steven J Lobritto
- Department of Pediatrics, Columbia University Medical Center, New York, New York, USA
| | - Caroline Lemoine
- Department of Surgery, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA
| | - Janis M Stoll
- Department of Pediatrics, St. Louis Children's Hospital and Washington University School of Medicine, St. Louis, Missouri, USA
| | - Bernadette E Vitola
- Department of Pediatrics, Medical College of Wisconsin and Children's Hospital of Wisconsin, Milwaukee, Wisconsin, USA
| | - James F Daniel
- Department of Pediatrics, Children's Mercy Hospital, Kansas City, Missouri, USA
| | - Blayne A Sayed
- Department of Surgery, University Health Network and the Hospital for Sick Children, Toronto, Ontario, Canada
| | - Dev M Desai
- Department of Surgery, University of Texas Southwestern Medical Center and Children's Medical Center, Dallas, Texas, USA
| | - Abigail E Martin
- Department of Surgery, Nemours Children's Hospital Delaware and Sidney Kimmel Medical College of Thomas Jefferson University, Wilmington, Delaware, USA
| | - Arpit Amin
- Department of Surgery, University of Pittsburgh Medical Center Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | | | | | - Shikha S Sundaram
- Department of Pediatrics, Children's Hospital Colorado and University of Colorado, Aurora, Colorado, USA
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13
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Özçay F, Balci Sezer O, Sarialioğlu F, Boyvat F, Coşkun M, Haberal Reyhan N, Haberal M. Seventeen Years of Pediatric Liver Transplantation Experience for Cirrhosis and Hepatocellular Carcinoma. EXP CLIN TRANSPLANT 2022. [PMID: 35297328 DOI: 10.6002/ect.2021.0469] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
OBJECTIVES This was a retrospective analysis of liver transplant for pediatric patients with liver cirrhosis and hepatocellular carcinoma. MATERIALS AND METHODS Fourteen pediatric patients with chronic liver disease and hepatocellular carcinoma underwent liver transplant from 2004 to 2021. Preexisting diseases were tyrosinemia (n = 6), progressive familial intrahepatic cholestasis type 2 (n = 2) and type 3 (n = 3), cryptogenic cirrhosis (n = 2), hepatitis B and D (n = 1), and biliary atresia (n = 1). RESULTS Mean age was 9.43 ± 4.9 years (range, 13 months to 16 years). Three patients had 1 tumor, 4 had 2 tumors, and 7 had multiple (≥3) lesions. Six patients were classified as Pretreatment Extent of Disease Staging System for Hepatoblastoma (PRETEXT) stage IV, 3 as stage II, and 5 as stage I. Some patients received systemic chemotherapy before (n = 4) or after transplant (n = 3) or transarterial chemoembolization and microwave ablation pretransplant (n = 1). Hepatocellular carcinoma posttransplant recurrence was observed at 23, 47, and 108 months in 3 patients (21%). Recurrence sites were omentum (n = 1) and liver graft (n = 2). One patient was treated with hepatic resection, radiofrequency ablation, and radiotherapy, while the other received radiofrequency ablation and chemotherapy for graft tumor recurrence. Relapse-free patient survival rates were 92%, 82.5%, and 72.2% at 2, 4, and 10 years, respectively. Four recipients (28.5%) died; posttransplant cause of death was infection at 19 (n = 1) and 188 months (n = 1) or hepatocellular carcinoma recurrence at 79 (n = 1) and 165 months (n = 1). Median follow-up was 178 months (range, 13-204 months). Mean estimated survival was 171.25 ± 16.6 months. Overall patient posttransplant survival was 100%, 92.3%, 92.3%, 83%, and 72% at 1, 2, 5, 10, and 15 years, respectively. CONCLUSIONS Hepatocellular carcinoma was mainly associated with inherited liver diseases in our pediatric series. Liver transplant provided a long-term survival advantage to pediatric patients with preexisting cirrhosis and hepatocellular carcinoma.
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Affiliation(s)
- Figen Özçay
- From the Department of Pediatric Gastroenterology, Başkent University, Ankara, Turkey
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14
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Kakos CD, Ziogas IA, Demiri CD, Esagian SM, Economopoulos KP, Moris D, Tsoulfas G, Alexopoulos SP. Liver Transplantation for Pediatric Hepatocellular Carcinoma: A Systematic Review. Cancers (Basel) 2022; 14:1294. [PMID: 35267604 PMCID: PMC8908995 DOI: 10.3390/cancers14051294] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2022] [Revised: 02/23/2022] [Accepted: 02/28/2022] [Indexed: 02/05/2023] Open
Abstract
Liver transplantation (LT) is the only potentially curative option for children with unresectable hepatocellular carcinoma (HCC). We performed a systematic review of the MEDLINE, Scopus, Cochrane Library, and Web of Science databases (end-of-search date: 31 July 2020). Our outcomes were overall survival (OS) and disease-free survival (DFS). We evaluated the effect of clinically relevant variables on outcomes using the Kaplan-Meier method and log-rank test. Sixty-seven studies reporting on 245 children undergoing LT for HCC were included. DFS data were available for 150 patients and the 1-, 3-, and 5-year DFS rates were 92.3%, 89.1%, and 84.5%, respectively. Sixty of the two hundred and thirty-eight patients (25.2%) died over a mean follow up of 46.8 ± 47.4 months. OS data were available for 222 patients and the 1-, 3-, and 5-year OS rates were 87.9%, 78.8%, and 74.3%, respectively. Although no difference was observed between children transplanted within vs. beyond Milan criteria (p = 0.15), superior OS was observed in children transplanted within vs. beyond UCSF criteria (p = 0.02). LT can yield favorable outcomes for pediatric HCC beyond Milan but not beyond UCSF criteria. Further research is required to determine appropriate LT selection criteria for pediatric HCC.
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Affiliation(s)
- Christos D. Kakos
- Surgery Working Group, Society of Junior Doctors, 15123 Athens, Greece; (C.D.K.); (I.A.Z.); (C.D.D.); (S.M.E.); (K.P.E.)
| | - Ioannis A. Ziogas
- Surgery Working Group, Society of Junior Doctors, 15123 Athens, Greece; (C.D.K.); (I.A.Z.); (C.D.D.); (S.M.E.); (K.P.E.)
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Charikleia D. Demiri
- Surgery Working Group, Society of Junior Doctors, 15123 Athens, Greece; (C.D.K.); (I.A.Z.); (C.D.D.); (S.M.E.); (K.P.E.)
- 2nd Department of Pediatric Surgery, “Papageorgiou” General Hospital, Aristotle University School of Medicine, 54124 Thessaloniki, Greece
| | - Stepan M. Esagian
- Surgery Working Group, Society of Junior Doctors, 15123 Athens, Greece; (C.D.K.); (I.A.Z.); (C.D.D.); (S.M.E.); (K.P.E.)
| | - Konstantinos P. Economopoulos
- Surgery Working Group, Society of Junior Doctors, 15123 Athens, Greece; (C.D.K.); (I.A.Z.); (C.D.D.); (S.M.E.); (K.P.E.)
- Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA;
| | - Dimitrios Moris
- Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA;
| | - Georgios Tsoulfas
- Department of Surgery, Aristotle University School of Medicine, 54124 Thessaloniki, Greece;
| | - Sophoclis P. Alexopoulos
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Vanderbilt University Medical Center, Nashville, TN 37232, USA
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15
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Wu WK, Ziogas IA, Matsuoka LK, Izzy M, Pai AK, Benedetti DJ, Alexopoulos SP. Waitlist mortality and post-liver transplant outcomes of pediatric patients with hepatocellular carcinoma and hepatoblastoma in the United States. Pediatr Blood Cancer 2022; 69:e29425. [PMID: 34736292 DOI: 10.1002/pbc.29425] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Revised: 09/21/2021] [Accepted: 10/10/2021] [Indexed: 11/09/2022]
Abstract
BACKGROUND Liver transplantation (LT) is offered in cases of advanced disease for both pediatric patients with hepatoblastoma (HBL) and those with hepatocellular carcinoma (HCC). Current United States organ allocation priorities differ between the two groups. METHODS We retrospectively examined the waitlist and posttransplant outcomes of pediatric LT candidates with HBL and HCC using the United Network for Organ Sharing registry (February 2002 to September 2020). RESULTS Six hundred sixty-eight children with HBL and 95 children with HCC listed for first LT were identified. Patients with HBL were younger (p < .001), had lower laboratory Model for End-stage Liver Disease (MELD)/Pediatric End-stage Liver Disease (PELD) scores (p < .001), and had lesser proportion with encephalopathy (p = .01). Patients with HCC had an increased risk of waitlist mortality in univariable (unadjusted subdistribution hazard ratio [sHR] = 4.37, 95% confidence interval [CI], 2.01-9.51, p < .001) and multivariable competing risk regression (adjusted sHR = 3.08, 95% CI 1.13-8.37, p = .03) accounting for age and laboratory MELD/PELD score. Five hundred ninety-five children underwent LT for HBL and 76 for HCC. Patients transplanted for HBL had a significantly higher proportion with status 1B exception (71.3% vs. 7.9%, p < .001). No difference was observed in patient (unadjusted log-rank test, p = .52; adjusted hazard ratio [HR] = 0.77, 95% CI, 0.40-1.48, p = .43) or graft survival (unadjusted log-rank test, p = .93; adjusted HR = 0.74, 95% CI 0.42-1.33, p = .32) between HCC and HBL recipients. CONCLUSION Waitlist mortality for pediatric LT candidates with HCC is significantly higher than for HBL, while posttransplant patient and graft survival are similar. This highlights an opportunity to improve equitable prioritization for children with HCC who may have reduced access to size-appropriate deceased donor organs and less effective bridge-to-transplant therapies.
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Affiliation(s)
- W Kelly Wu
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Ioannis A Ziogas
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Lea K Matsuoka
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Manhal Izzy
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Anita K Pai
- Department of Pediatrics, D. Brent Polk Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Daniel J Benedetti
- Department of Pediatrics, Division of Hematology-Oncology, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Sophoclis P Alexopoulos
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Vanderbilt University Medical Center, Nashville, Tennessee, USA
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16
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Pire A, Tambucci R, De Magnée C, Sokal E, Stephenne X, Scheers I, Zech F, Gurevich M, Brichard B, Reding R. Living donor liver transplantation for hepatic malignancies in children. Pediatr Transplant 2021; 25:e14047. [PMID: 34076944 DOI: 10.1111/petr.14047] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2021] [Revised: 05/03/2021] [Accepted: 05/04/2021] [Indexed: 12/21/2022]
Abstract
BACKGROUND Living donor liver transplantation is a treatment option for unresectable hepatic tumors in children. METHODS We enrolled 45 living donor transplantations performed between 1993 and 2018 for liver malignacies, which included hepatoblastoma (n = 33), hepatocellular carcinoma (n = 10), hepatic angiosarcoma (n = 1), and rhabdomyosarcoma (n = 1). RESULTS No mortality or major morbidities were encountered in any donor, and the complication rate was 9%. In the hepatoblastoma group, 5-year overall and event-free survival rate in recipients was 87.4% and 75.8%, respectively, and mortality was significantly higher in patients after rescue transplantation (p = .001). Inferior vena cava replacement in these recipients appeared to be associated with reduced mortality (p = .034), but this was not confirmed when rescue patients were excluded (p = .629). In hepatocellular carcinoma group, both 5-year overall and event-free survival rates were 75.4% each, and invasion of hepatic veins was significantly associated with increased risk of recurrence and death (p = .028). The patient with rhabdomyosarcoma died from EBV-induced lymphoma 2 months after transplantation. The patient with angiosarcoma was in complete remission at the last follow-up. Overall, 5-year graft survival rate was 81.3%, and one patient underwent re-transplantation due to chronic rejection. CONCLUSIONS Pediatric oncological liver transplantation has become a key player in the management of malignancies with cancer cure in 84% of patients in this series. Living donor liver transplantation for pediatric recipients with unresectable tumors might be a beneficial surgical option, which is technically safe for donors and recipients, thus, allowing timely planning according to chemotherapy protocols.
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Affiliation(s)
- Aurore Pire
- Pediatric and Transplantation Surgery, Cliniques Universitaires Saint-Luc, Brussels, Belgium
| | - Roberto Tambucci
- Pediatric and Transplantation Surgery, Cliniques Universitaires Saint-Luc, Brussels, Belgium
| | - Catherine De Magnée
- Pediatric and Transplantation Surgery, Cliniques Universitaires Saint-Luc, Brussels, Belgium
| | - Etienne Sokal
- Pediatric Hepatology and Gastroenterology, Cliniques Universitaires Saint-Luc, Brussels, Belgium
| | - Xavier Stephenne
- Pediatric Hepatology and Gastroenterology, Cliniques Universitaires Saint-Luc, Brussels, Belgium
| | - Isabelle Scheers
- Pediatric Hepatology and Gastroenterology, Cliniques Universitaires Saint-Luc, Brussels, Belgium
| | - Francis Zech
- Institute of Experimental and Clinical Research, Université Catholique de Louvain, Brussels, Belgium
| | - Micheal Gurevich
- Organ Transplantation Division, Schneider Children's Medical Center of Israel, Petah Tikva, Israel
| | - Bénédicte Brichard
- Pediatric Oncology, Cliniques Universitaires Saint-Luc, Brussels, Belgium
| | - Raymond Reding
- Pediatric and Transplantation Surgery, Cliniques Universitaires Saint-Luc, Brussels, Belgium
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17
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Abstract
Malignant primary liver tumors are rare in children. Yet a wide histologic spectrum is seen, particularly in hepatoblastoma, the most common malignant liver tumor in children. Furthermore, there can be significant morphologic overlap with hepatocellular carcinoma, the second most common pediatric liver malignancy, and tumors with hybrid features of hepatoblastoma and hepatocellular carcinoma are also reported (currently placed in the provisional category of malignant hepatocellular neoplasm, not otherwise specified). This review provides detailed morphologic descriptions and updates in the evolving clinical context of these tumors, and presents recent molecular advances that may further help in accurate classification of these tumors, which is critical in their management.
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Affiliation(s)
- Soo-Jin Cho
- Department of Pathology, University of California San Francisco, 1825 4th Street Room M2369, Box 4066, San Francisco, CA 94143, USA.
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18
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Uchida H, Sakamoto S, Kasahara M, Ueno Y, Mochida S, Haga H, Okajima H, Eguchi S, Takada Y, Umeshita K, Kokudo N, Egawa H, Uemoto S, Ohdan H. An analysis of the outcomes in living donor liver transplantation for pediatric malignant hepatic tumors using nationwide survey data in Japan. Transpl Int 2021; 34:1408-1421. [PMID: 34021931 DOI: 10.1111/tri.13924] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Revised: 05/17/2021] [Accepted: 05/18/2021] [Indexed: 12/22/2022]
Abstract
Malignant hepatic tumors (MHTs) in children are rare and account for approximately 5% of candidates for pediatric liver transplantation (LT) in Japan. We conducted a national survey of pediatric patients undergoing living donor LT for MHTs between October 1990 and April 2018. In total, 116 children underwent LT for MHTs during this study period: 100 hepatoblastomas (HBLs), 10 hepatocellular carcinomas (HCCs), and six other MHTs. The overall patient survival rate at 5 years was 81.3% for HBL, 60.0% for HCC, and 80.0% for other MHTs (P = 0.047). In patients with HBL, there was no significant difference in the 1- and 5-year patient survival rates between patients undergoing primary LT and those who received salvage LT for tumor recurrence (89.7%, 81.6% vs. 88.0%, 76%; P = 0.526). The 5-year overall survival rate after LT for HBL significantly improved from 63.2% in 1996-2008 to 89.8% in 2009-2018 (P = 0.018). The presence of lung metastasis before LT had no significant influence on the long-term survival (P = 0.742). Five patients with HCC died, including two who fell outside the Milan criteria. In conclusion, LT for pediatric MHTs, especially HBL, is a valuable treatment option for select patients.
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Affiliation(s)
- Hajime Uchida
- Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
| | - Seisuke Sakamoto
- Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
| | - Mureo Kasahara
- Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
| | - Yoshiyuki Ueno
- Department of Gastroenterology, Faculty of Medicine, Yamagata University, Yamagata, Japan
| | - Satoshi Mochida
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, Saitama, Japan
| | - Hironori Haga
- Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan
| | - Hideaki Okajima
- Department of Pediatric Surgery, Kanazawa Medical University, Ishikawa, Japan
| | - Susumu Eguchi
- Department of Surgery, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
| | - Yasutsugu Takada
- Department of Hepato-Biliary-Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
| | - Koji Umeshita
- Department of Surgery, Osaka University, Osaka, Japan
| | - Norihiro Kokudo
- Department of Surgery, National Center for Global Health and Medicine, Tokyo, Japan
| | - Hiroto Egawa
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | | | - Hideki Ohdan
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
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19
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Abstract
PURPOSE Pediatric hepatocellular carcinoma is rarely seen in childhood. It constitutes approximately 1% of childhood solid organ malignancies. Pediatric hepatocellular carcinoma is the second most common malignant liver tumor after hepatoblastoma in children. In this review, we aimed to review the diagnosis and treatment of pediatric hepatocellular carcinoma in the light of the latest literature. METHODS We reviewed the literature in terms of the diagnosis and treatment of pediatric hepatocellular carcinoma. RESULTS Hepatocellular carcinoma (HCC) and hepatoblastoma constitute 0.5-1.5% of all childhood malignant tumors. HCC is responsible for 27% of all liver tumors and 4% of all pediatric liver transplantations. While 99.6% of HCC is seen in adults, only 0.4% of it is seen in pediatric patients. Etiological predisposition and biological behavior are different from adults. In a child with cirrhosis or liver disease, HCC should be suspected in the presence of a high level of AFP and an abnormal nodule on ultrasonography. Hepatoblastoma should be considered first in the differential diagnosis. CONCLUSION Treatment of pediatric HCC is challenging. Complete surgical resection is essential for the cure. To this end, different neoadjuvant chemotherapy protocols have been designed to convert non-resectable tumors into resectable tumors. For tumors that cannot be resected, liver transplantation for each patient with childhood HCC should be decided individually.
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Affiliation(s)
- Fatma İlknur Varol
- Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Faculty of Medicine, Inonu University, 244280, Malatya, Turkey.
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20
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Ziogas IA, Benedetti DJ, Matsuoka LK, Izzy M, Rauf MA, Pai AK, Bailey CE, Alexopoulos SP. Surgical management of pediatric hepatocellular carcinoma: An analysis of the National Cancer Database. J Pediatr Surg 2021; 56:772-777. [PMID: 32660779 DOI: 10.1016/j.jpedsurg.2020.06.013] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2020] [Revised: 06/03/2020] [Accepted: 06/07/2020] [Indexed: 12/16/2022]
Abstract
PURPOSE This study evaluates overall survival (OS) between liver transplantation (LT) and liver resection (LR), while assessing the effect of margin status, in children with hepatocellular carcinoma (HCC). METHODS The National Cancer Database was queried (2004-2015) for children (<18 years) with non-metastatic HCC undergoing surgery. RESULTS One hundred six children with HCC treated surgically (LT 34, LR 72) were identified. For T1 stage, no difference in OS was observed for LT vs. margin-negative liver resection [LR(-)] (log-rank, p = 0.47). For T2/T3/T4 stage, no difference in OS was observed for LT vs. LR(-) (log-rank, p = 0.08); both subgroups exhibited superior OS vs. margin-positive liver resection [LR(+)] (log-rank, LT vs. LR(+): p = 0.001 and LR(-) vs. LR(+): p = 0.04). On multivariable Cox regression: (i) histology (fibrolamellar vs. not) and T stage (T1 vs. T2/T3/T4) were not associated with OS (both p = 0.06), (ii) chemotherapy and size >5 cm were not associated with OS (both p ≥ 0.42), (iii) when compared to LT, both LR(-) (p = 0.03) and LR(+) (p = 0.001) were associated with increased likelihood of mortality. CONCLUSION Although margin-negative resection may be obtained with LT or LR, early LT consultation is warranted for children at high risk of LR(+) regardless of Milan criteria due to the negative impact of LR(+) on OS. TYPE OF STUDY Retrospective cohort study. LEVEL OF EVIDENCE III.
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Affiliation(s)
- Ioannis A Ziogas
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Daniel J Benedetti
- Department of Pediatrics, Division of Hematology-Oncology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Lea K Matsuoka
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Manhal Izzy
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Muhammad A Rauf
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Anita K Pai
- Department of Pediatrics, D. Brent Polk Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Christina E Bailey
- Department of Surgery, Division of Surgical Oncology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Sophoclis P Alexopoulos
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
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21
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Kelgeri C, Renz D, McGuirk S, Schmid I, Sharif K, Baumann U. Liver Tumours in Children: The Hepatologist's View. J Pediatr Gastroenterol Nutr 2021; 72:487-493. [PMID: 33264187 DOI: 10.1097/mpg.0000000000003006] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
ABSTRACT Diagnostic and therapeutic innovations have changed the way we now approach liver tumours in children and adolescents. Novel imaging tools, increasing awareness, and surveillance has led to early diagnosis of benign and malignant liver tumours. Multidisciplinary interventions have favourably altered the natural course in some liver tumours. The role of liver transplantation is expanding and has become fully integrated into today's therapeutic algorithms. Transarterial locoregional and ablation therapies have been successful in adults and are being explored in children to facilitate resectability and improve outcome. For the first time, North American, Japanese, and European experts have designed a global trial to optimize management of malignant liver tumours and aim to find signature molecular profiles that will translate to individualised treatment strategies.This article aims to offer an overview of recent advances in our understanding of liver tumours in children. It focuses on the paediatric hepatologist's view and their role in the multidisciplinary management of benign and malignant liver tumours.
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Affiliation(s)
- Chayarani Kelgeri
- Paediatric Liver Unit including Intestinal Transplantation, Birmingham Women's and Children's NHS Foundation Trust, UK
| | - Diane Renz
- Institute of Diagnostic and Interventional Radiology, Department of Paediatric Radiology, Medizinische Hochschule Hannover, Germany
| | - Simon McGuirk
- Department of Radiology, Birmingham Women's and Children's NHS Foundation Trust, Birmingham, UK
| | - Irene Schmid
- Paediatric Oncology, Ludwig Maximilians University, Munich, Germany
| | - Khalid Sharif
- Paediatric Liver Unit including Intestinal Transplantation, Birmingham Women's and Children's NHS Foundation Trust, Birmingham, UK
| | - Ulrich Baumann
- Paediatric Gastroenterology and Hepatology, Medizinische Hochschule Hannover, Germany
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22
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Bryan N, Zandieh A, Kallakury B, Kaufman S, Yazigi N, Girlanda R, Hawksworth J, Fishbein T, Matsumoto C, Kroemer A, Khan K. De novo hepatocellular carcinoma 18 years after liver and small bowel transplantation in a one-year-old pediatric patient. Pediatr Transplant 2021; 25:e13820. [PMID: 32844551 DOI: 10.1111/petr.13820] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2020] [Revised: 06/30/2020] [Accepted: 07/02/2020] [Indexed: 11/29/2022]
Abstract
De novo HCC following transplantation in a child is a rare occurrence. Even within the adult liver transplantation population, there are a limited number of published cases. In this report, we present a case of de novo HCC found in a child, post-multivisceral transplantation. A 19-year-old boy, at the age of one, received liver and small bowel transplantation due to short gut syndrome secondary to midgut volvulus and total parenteral nutrition-associated liver disease. Eighteen years later, he was found to have a large mass involving the right hepatic dome consistent with HCC. To the best of our knowledge, this is the second reported case after gut transplantation and the third case post-liver transplantation in the pediatric population.
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Affiliation(s)
- Nathan Bryan
- Department of Pediatrics, Medstar Georgetown University Hospital, Washington, DC, USA
| | - Arash Zandieh
- Department of Pediatrics, Medstar Georgetown University Hospital, Washington, DC, USA
| | - Bhaskar Kallakury
- Department of Pediatrics, Medstar Georgetown University Hospital, Washington, DC, USA
| | - Stuart Kaufman
- Department of Pediatrics, Medstar Georgetown University Hospital, Washington, DC, USA
| | - Nada Yazigi
- Department of Pediatrics, Medstar Georgetown University Hospital, Washington, DC, USA
| | - Rafaele Girlanda
- Department of Pediatrics, Medstar Georgetown University Hospital, Washington, DC, USA
| | - Jason Hawksworth
- Department of Pediatrics, Medstar Georgetown University Hospital, Washington, DC, USA
| | - Thomas Fishbein
- Department of Pediatrics, Medstar Georgetown University Hospital, Washington, DC, USA
| | - Cal Matsumoto
- Department of Pediatrics, Medstar Georgetown University Hospital, Washington, DC, USA
| | - Alexander Kroemer
- Department of Pediatrics, Medstar Georgetown University Hospital, Washington, DC, USA
| | - Khalid Khan
- Department of Pediatrics, Medstar Georgetown University Hospital, Washington, DC, USA
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23
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Lerut J, Karam V, Cailliez V, Bismuth H, Polak WG, Gunson B, Adam R. What did the European Liver Transplant Registry bring to liver transplantation? Transpl Int 2020; 33:1369-1383. [PMID: 32767799 DOI: 10.1111/tri.13716] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2020] [Revised: 07/06/2020] [Accepted: 08/04/2020] [Indexed: 11/30/2022]
Abstract
Since its foundation in 1985, the European Liver Transplant Registry has evolved to become an important tool to monitor the liver transplantation activity in Europe. The vast amount of data collected on 169 473 liver transplantations performed in 153 238 recipients has also resulted in scientific publications. Without doubt, several of these have influenced the daily practice of liver transplantation. This paper gives an overview of the development, the functioning, and the scientific activity of the European Liver Transplant Registry during more than three decades. Indeed, it can be said that the registry helped to advance the practice of liver transplantation not only in Europe but also worldwide.
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Affiliation(s)
- Jan Lerut
- Institut de Recherche Expérimentale et Clinique (IREC), Université catholique de Louvain, Brussels, Belgium
| | - Vincent Karam
- European Liver Transplant Registry, INSERM U 935, APHP Hôpital Paul Brousse, Université Paris-Saclay, Villejuif, France
| | - Valérie Cailliez
- European Liver Transplant Registry, INSERM U 935, APHP Hôpital Paul Brousse, Université Paris-Saclay, Villejuif, France
| | - Henri Bismuth
- European Liver Transplant Registry, INSERM U 935, APHP Hôpital Paul Brousse, Université Paris-Saclay, Villejuif, France
| | - Wojciech G Polak
- Division of Hepatopancreatobiliary and Transplant Surgery, Department of Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Bridget Gunson
- Liver Unit and National Institute of Health Research Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, University of Birmingham, Birmingham, UK
| | - Rene Adam
- European Liver Transplant Registry, INSERM U 935, APHP Hôpital Paul Brousse, Université Paris-Saclay, Villejuif, France
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24
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Ziogas IA, Ye F, Zhao Z, Matsuoka LK, Montenovo MI, Izzy M, Benedetti DJ, Lovvorn HN, Gillis LA, Alexopoulos SP. Population-Based Analysis of Hepatocellular Carcinoma in Children: Identifying Optimal Surgical Treatment. J Am Coll Surg 2020; 230:1035-1044.e3. [PMID: 32272204 DOI: 10.1016/j.jamcollsurg.2020.03.024] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2019] [Revised: 03/05/2020] [Accepted: 03/06/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) constitutes 0.5% of childhood malignancies and exhibits poor prognosis. Complete tumor extirpation either by partial liver resection (LR) or liver transplantation (LT) is the only curative treatment. Due to the poor initial outcomes of LT, LR has remained the mainstay of treatment for all but select children fulfilling the Milan criteria (originally designed for adults). METHODS We conducted a retrospective cohort study of pediatric HCC patients (younger than 18 years of age) registered in the Surveillance, Epidemiology, and End Results database between 2004 and 2015. Survival analysis was performed by means of Kaplan-Meier methods, 2-sided stratified log-rank tests, and Cox regression models. RESULTS Of 127 children with HCC, 46 did not undergo operation (36.2%), 32 underwent LT (25.2%), and 49 underwent LR (38.6%). Using the Kaplan-Meier method, the 5-year cancer-specific survival (CSS) rates for LT and LR were 87% and 63%, respectively. LT exhibited superior CSS vs LR (log-rank, p = 0.007). For T1 stage, LT showed equivalent CSS compared with LR (log-rank, p = 0.23), and for T2 and T3 stage, LT exhibited superior CSS (log-rank, p = 0.047 and p = 0.01, respectively). On multivariable Cox regression analysis, T3/T4 stage (adjusted hazard ratio 13.63; 95% CI, 2.9 to 64.07; p = 0.001), and LR (adjusted hazard ratio 7.51; 95% CI, 2.07 to 27.29; p = 0.002) were found to be independently associated with cancer-specific mortality. Fibrolamellar histology and lymph node status were not found to be associated with mortality. CONCLUSIONS Our findings suggest that children diagnosed with nonmetastatic advanced-stage HCC have a favorable prognosis after LT compared with LR. Early inclusion of an LT consultation after the initial diagnosis is warranted, especially in children with unresectable HCC or when complete tumor extirpation with LR is not feasible.
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Affiliation(s)
- Ioannis A Ziogas
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Vanderbilt University Medical Center, Nashville, TN
| | - Fei Ye
- Center for Quantitative Sciences and Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN
| | - Zhiguo Zhao
- Center for Quantitative Sciences and Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN
| | - Lea K Matsuoka
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Vanderbilt University Medical Center, Nashville, TN
| | - Martin I Montenovo
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Vanderbilt University Medical Center, Nashville, TN
| | - Manhal Izzy
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, Nashville, TN
| | - Daniel J Benedetti
- Department of Pediatrics, Division of Hematology-Oncology, Vanderbilt University Medical Center, Nashville, TN
| | - Harold N Lovvorn
- Department of Pediatrics, D. Brent Polk Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, TN
| | - Lynette A Gillis
- Department of Pediatric Surgery, Monroe Carell, Jr. Children's Hospital at Vanderbilt, Nashville, TN
| | - Sophoclis P Alexopoulos
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Vanderbilt University Medical Center, Nashville, TN.
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25
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Tiusanen T, Hukkinen M, Leskinen O, Soini T, Kanerva JA, Jahnukainen T, Mäkisalo H, Heikinheimo M, Pakarinen MP. Incidence and long-term outcomes of surgically treated childhood hepatic malignancies in Finland. Acta Paediatr 2020; 109:404-414. [PMID: 31350767 DOI: 10.1111/apa.14952] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2019] [Revised: 06/06/2019] [Accepted: 07/24/2019] [Indexed: 12/12/2022]
Abstract
AIM To analyse incidence, treatment and outcomes of paediatric liver malignancies in Finland during 1987-2017. METHODS Medical records and national cancer registry data of 47 children with liver malignancies were reviewed. Survival was calculated with the Kaplan-Meier method. RESULTS During follow-up, liver malignancy incidence remained stable at 1.1:106 . Altogether, 42 patients with hepatoblastoma (n = 24), hepatocellular carcinoma (n = 11) and undifferentiated embryonal sarcoma (n = 7) underwent surgery at median age 4.6 (interquartile range, 2.0-9.6) years and were followed up for 13 (7.0-19) years. Cumulative 5-year survival was 86% for hepatoblastoma, 41% for hepatocellular carcinoma and 67% for undifferentiated embryonal sarcoma. Five-year survival was decreased among hepatoblastoma patients aged ≥ 2.4 years (73% versus 100%, P = .040), with PRETreatment EXTent of disease IV (PRETEXT, 60% vs 100%, P = .004), and with recurrent disease (67% vs 88%, P = .029). Recurrent/residual disease associated with decreased 5-year survival in hepatocellular carcinoma (0% vs 83%, P = .028). Survival was similar among 19 transplanted and 23 resected patients. In total, 14 deaths occurred either for the underlying malignancy (n = 8), adverse effects of chemotherapy (n = 5) or unrelated reasons (n = 1). CONCLUSION Outcomes for PRETEXT I-III hepatoblastoma and un-metastasized hepatocellular carcinoma were encouraging. Adverse effects of chemotherapy significantly contributed to mortality.
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Affiliation(s)
- Toivo Tiusanen
- Pediatric Liver and Gut Research Group Children's Hospital Helsinki University Hospital University of Helsinki Helsinki Finland
- Pediatric Research Center Children's Hospital Helsinki University Hospital University of Helsinki Helsinki Finland
| | - Maria Hukkinen
- Pediatric Liver and Gut Research Group Children's Hospital Helsinki University Hospital University of Helsinki Helsinki Finland
- Pediatric Research Center Children's Hospital Helsinki University Hospital University of Helsinki Helsinki Finland
- Section of Pediatric Surgery Children's Hospital Helsinki University Hospital University of Helsinki Helsinki Finland
| | - Outi Leskinen
- HUS Medical Imaging Center Children's Hospital Helsinki University Hospital University of Helsinki Helsinki Finland
| | - Tea Soini
- Pediatric Research Center Children's Hospital Helsinki University Hospital University of Helsinki Helsinki Finland
| | - Jukka A. Kanerva
- Pediatric Research Center Children's Hospital Helsinki University Hospital University of Helsinki Helsinki Finland
| | - Timo Jahnukainen
- Pediatric Research Center Children's Hospital Helsinki University Hospital University of Helsinki Helsinki Finland
- Department of Pediatric Nephrology and Transplantation Children's Hospital Helsinki University Hospital University of Helsinki Helsinki Finland
| | - Heikki Mäkisalo
- Department of Liver and Transplantation Surgery University Hospital University of Helsinki Helsinki Finland
| | - Markku Heikinheimo
- Pediatric Research Center Children's Hospital Helsinki University Hospital University of Helsinki Helsinki Finland
- Department of Pediatrics Washington University St. Louis MO USA
| | - Mikko P. Pakarinen
- Pediatric Liver and Gut Research Group Children's Hospital Helsinki University Hospital University of Helsinki Helsinki Finland
- Pediatric Research Center Children's Hospital Helsinki University Hospital University of Helsinki Helsinki Finland
- Section of Pediatric Surgery Children's Hospital Helsinki University Hospital University of Helsinki Helsinki Finland
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26
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Lleo A, de Boer YS, Liberal R, Colombo M. The risk of liver cancer in autoimmune liver diseases. Ther Adv Med Oncol 2019; 11:1758835919861914. [PMID: 31320937 PMCID: PMC6628541 DOI: 10.1177/1758835919861914] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2019] [Accepted: 06/13/2019] [Indexed: 12/13/2022] Open
Abstract
Hepatocellular carcinoma (HCC), the dominant primary malignancy of the liver, has almost invariably a fatal outcome that can be averted only by early diagnosis and treatment. While the close association of HCC with chronic viral hepatitis and alcohol abuse has impacted favourably on screening and treatment of this deadly tumour, at the same time it has long obscured the etiologic role of autoimmune liver diseases. Recently, a systematic analysis of 25 published cohorts disclosed a 3.1 × 1000 patients/year incidence of HCC in autoimmune hepatitis patients that tripled in those with cirrhosis. HCC is also a sequela of primary biliary cholangitis, where the incidence is more relevant in males, those with advanced liver disease and nonresponders to ursodeoxycholic acid therapy. Cholangiocarcinoma (CCA), the second ranking primary cancer of the liver, is also on the rise with its intrahepatic pattern, in part reflecting an association with chronic liver diseases of diverse aetiology. In the USA and northern Europe, perihilar CCA is a frequent complication of primary sclerosing cholangitis, a cholestatic disorder thought to be immune mediated. International Guidelines clearly recommend HCC screening with abdominal ultrasonography every 6 months in autoimmune cirrhotic patients. While surveillance of patients with autoimmune liver disorders who are at risk of HCC affects both early diagnosis and radical therapy of this tumour, this is not the case for CCA, where early diagnosis is challenged by the lack of sensitive and accurate tests for screening.
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Affiliation(s)
- Ana Lleo
- Department of Biomedical Sciences, Humanitas
University, Division of Internal Medicine and Hepatology, Department of
Gastroenterology, Humanitas Clinical and Research Center IRCCS, Via A.
Manzoni 56, 20089 Rozzano (MI), Italy
| | - Ynto S. de Boer
- Department of Gastroenterology and Hepatology,
Amsterdam University Medical Centers - VU University Medical Center, The
Netherlands
| | | | - Massimo Colombo
- Humanitas Clinical and Research Center, IRCCS,
Rozzano, Italy
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27
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Agazzi R, Tessitore P, Sironi S. Diagnostic and Interventional Radiology. PEDIATRIC HEPATOLOGY AND LIVER TRANSPLANTATION 2019:67-97. [DOI: 10.1007/978-3-319-96400-3_5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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28
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Chen HL, Wu SH, Hsu SH, Liou BY, Chen HL, Chang MH. Jaundice revisited: recent advances in the diagnosis and treatment of inherited cholestatic liver diseases. J Biomed Sci 2018; 25:75. [PMID: 30367658 PMCID: PMC6203212 DOI: 10.1186/s12929-018-0475-8] [Citation(s) in RCA: 93] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2018] [Accepted: 10/03/2018] [Indexed: 12/17/2022] Open
Abstract
Background Jaundice is a common symptom of inherited or acquired liver diseases or a manifestation of diseases involving red blood cell metabolism. Recent progress has elucidated the molecular mechanisms of bile metabolism, hepatocellular transport, bile ductular development, intestinal bile salt reabsorption, and the regulation of bile acids homeostasis. Main body The major genetic diseases causing jaundice involve disturbances of bile flow. The insufficiency of bile salts in the intestines leads to fat malabsorption and fat-soluble vitamin deficiencies. Accumulation of excessive bile acids and aberrant metabolites results in hepatocellular injury and biliary cirrhosis. Progressive familial intrahepatic cholestasis (PFIC) is the prototype of genetic liver diseases manifesting jaundice in early childhood, progressive liver fibrosis/cirrhosis, and failure to thrive. The first three types of PFICs identified (PFIC1, PFIC2, and PFIC3) represent defects in FIC1 (ATP8B1), BSEP (ABCB11), or MDR3 (ABCB4). In the last 5 years, new genetic disorders, such as TJP2, FXR, and MYO5B defects, have been demonstrated to cause a similar PFIC phenotype. Inborn errors of bile acid metabolism also cause progressive cholestatic liver injuries. Prompt differential diagnosis is important because oral primary bile acid replacement may effectively reverse liver failure and restore liver functions. DCDC2 is a newly identified genetic disorder causing neonatal sclerosing cholangitis. Other cholestatic genetic disorders may have extra-hepatic manifestations, such as developmental disorders causing ductal plate malformation (Alagille syndrome, polycystic liver/kidney diseases), mitochondrial hepatopathy, and endocrine or chromosomal disorders. The diagnosis of genetic liver diseases has evolved from direct sequencing of a single gene to panel-based next generation sequencing. Whole exome sequencing and whole genome sequencing have been actively investigated in research and clinical studies. Current treatment modalities include medical treatment (ursodeoxycholic acid, cholic acid or chenodeoxycholic acid), surgery (partial biliary diversion and liver transplantation), symptomatic treatment for pruritus, and nutritional therapy. New drug development based on gene-specific treatments, such as apical sodium-dependent bile acid transporter (ASBT) inhibitor, for BSEP defects are underway. Short conclusion Understanding the complex pathways of jaundice and cholestasis not only enhance insights into liver pathophysiology but also elucidate many causes of genetic liver diseases and promote the development of novel treatments.
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Affiliation(s)
- Huey-Ling Chen
- Departments of Pediatrics, National Taiwan University College of Medicine and Children's Hospital, 17F, No. 8, Chung Shan S. Rd, Taipei, 100, Taiwan. .,Department of Medical Education and Bioethics, National Taiwan University College of Medicine, No. 1, Jen Ai Rd Section 1, Taipei, 100, Taiwan. .,Hepatitis Research Center, National Taiwan University Hospital, Changde St. No.1, Zhongzhen Dist., Taipei 100, Taiwan.
| | - Shang-Hsin Wu
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, No. 7 Chung Shan S. Rd, Taipei 100, Taiwan
| | - Shu-Hao Hsu
- Graduate Institute of Anatomy and Cell Biology, Nationatl Taiwan University College of Medicine, No. 1 Jen Ai Rd Section 1, Taipei 100, Taiwan
| | - Bang-Yu Liou
- Departments of Pediatrics, National Taiwan University College of Medicine and Children's Hospital, 17F, No. 8, Chung Shan S. Rd, Taipei, 100, Taiwan
| | - Hui-Ling Chen
- Hepatitis Research Center, National Taiwan University Hospital, Changde St. No.1, Zhongzhen Dist., Taipei 100, Taiwan
| | - Mei-Hwei Chang
- Departments of Pediatrics, National Taiwan University College of Medicine and Children's Hospital, 17F, No. 8, Chung Shan S. Rd, Taipei, 100, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Changde St. No.1, Zhongzhen Dist., Taipei 100, Taiwan
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29
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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: 92] [Impact Index Per Article: 13.1] [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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30
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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 PMCID: PMC6182038 DOI: 10.21037/tgh.2018.09.05] [Citation(s) in RCA: 155] [Impact Index Per Article: 22.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [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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Weiss KE, Sze DY, Rangaswami AA, Esquivel CO, Concepcion W, Lebowitz EA, Kothary N, Lungren MP. Transarterial chemoembolization in children to treat unresectable hepatocellular carcinoma. Pediatr Transplant 2018; 22:e13187. [PMID: 29707868 DOI: 10.1111/petr.13187] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/26/2018] [Indexed: 01/20/2023]
Abstract
Children with unresectable HCC have a dismal prognosis and few approved treatment options. TACE is an effective treatment option for adults with HCC, but experience in children is very limited. Retrospective analysis was performed of 8 patients aged 4-17 years (4 male, mean 12.5 years) who underwent TACE for unresectable HCC. Response to TACE was evaluated by change in AFP, RECIST and tumor volume, PRETEXT, and transplantation eligibility by UCSF and Milan criteria. Post-procedure mean follow-up was 8.2 years. Mean overall change in tumor volume for the 8 patients was 51%. Percent change in AFP ranged from a decrease of 100% to an increase of 89.3%, with a mean change of -49.6%. Two patients did not undergo resection or transplantation and died of progressive disease. Six patients underwent orthotopic liver transplantation with mean first TACE-to-transplant interval of 141 days (range 11-514). Following transplantation, 5 patients were alive at the end of the follow-up period and one died of recurrent disease. Based on our initial experience, TACE for children with unresectable HCC appears to be a safe and effective method for managing hepatic tumor burden and for downstaging and bridging to liver transplantation.
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Affiliation(s)
- Krista E Weiss
- Division of Interventional Radiology, Stanford University Medical Center, Stanford, CA, USA
| | - Daniel Y Sze
- Division of Interventional Radiology, Stanford University Medical Center, Stanford, CA, USA
| | - Arun A Rangaswami
- Department of Pediatric Oncology, Stanford University Medical Center, Stanford, CA, USA
| | - Carlos O Esquivel
- Department of Pediatric Transplant Surgery, Stanford University Medical Center, Stanford, CA, USA
| | - Waldo Concepcion
- Department of Pediatric Transplant Surgery, Stanford University Medical Center, Stanford, CA, USA
| | - Edward A Lebowitz
- Division of Interventional Radiology, Stanford University Medical Center, Stanford, CA, USA
| | - Nishita Kothary
- Division of Interventional Radiology, Stanford University Medical Center, Stanford, CA, USA
| | - Matthew P Lungren
- Division of Interventional Radiology, Stanford University Medical Center, Stanford, CA, USA
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