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1
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Moghadamnia M, Dashti-Khavidaki S, Alimadadi H. Role of mTOR Inhibitors in Pediatric Liver Transplant Recipients: A Systematic Review. Paediatr Drugs 2024; 26:673-693. [PMID: 39251556 DOI: 10.1007/s40272-024-00648-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/27/2024] [Indexed: 09/11/2024]
Abstract
BACKGROUND Immunosuppressive medications play a crucial role in determining both organ and patient survival following liver transplantation (LT). Typically, immunosuppressive protocols for pediatric LT patients rely on calcineurin inhibitors (CNIs). While inhibitors of mammalian target of rapamycin (mTOR) have demonstrated beneficial outcomes in adult recipients of liver allografts, such as improved renal function post-LT, their application in pediatric liver transplant recipients is a subject of debate due to uncertain efficacy and potential adverse effects. OBJECTIVES This review evaluates the potential roles of mTOR inhibitors in the context of pediatric LT patients. METHODS This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol for conduct and reporting. Databases until 31 August 2023 were searched using specific terms and keywords. All clinical studies focusing on mTOR inhibitors in pediatric LT were included. RESULTS Out of 888 identified articles, 30 studies, involving 386 children who had undergone liver transplantation and received mTOR-inhibitor-based immunosuppressive regimens, met the inclusion criteria. The beneficial impacts of switching from a CNI to an mTOR inhibitor or adding an mTOR inhibitor to CNI-reduced immunosuppression in LT pediatric patients with impaired kidney function are controversial, and high-powered clinical studies are need. It appears that enhancing immunosuppression by adding an mTOR inhibitor to CNI is helpful for pediatric LT recipients who are experiencing refractory acute rejection or chronic rejection. mTOR-inhibitor-containing regimens failed to reduce the occurrence of post-transplant lymphoproliferative disorders (PTLD) among children with LT that may be due to concomitant high CNI concentration among studied patients. The effectiveness of mTOR inhibitors in treating PTLD remains uncertain; however, in patients with PTLD who are at high risk of rejection, mTOR inhibitors may be administered. Conversion to or the addition of mTOR inhibitors to maintenance immunosuppression seems to be suitable for pediatric patients who received a transplant due to hepatic malignancies such as hepatoblastoma or hepatocellular carcinoma or for those with post-transplant primary or recurrent malignancies. Switching to an mTOR inhibitor may improve some CNI-related adverse effects such as gingival hyperplasia, neurotoxicity, nephropathy, hypertrophic cardiomyopathy, or thrombotic microangiopathy. CONCLUSION Although the exact role of mTOR inhibitors among pediatric patients who have received a liver transplant needs further study, two algorithms are presented in this review to guide conversion from CNIs to mTOR inhibitors or the addition of mTOR inhibitor to a CNI-minimization immunosuppressive regimen for pediatric patients who may benefit from this class of drugs. This review mainly consisted of retrospective studies with inadequate sample sizes and lacked a control group, which represents the main limitation of this study.
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Affiliation(s)
- Marjan Moghadamnia
- Department of Pharmacotherapy, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Simin Dashti-Khavidaki
- Liver Transplantation Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
- Department of Clinical Pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
| | - Hosein Alimadadi
- Department of Gastroenterology, Children's Medical Center, Tehran University of Medical Science, Tehran, Iran
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2
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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 II. Diagnostics (Basel) 2023; 13:3659. [PMID: 38132242 PMCID: PMC10743166 DOI: 10.3390/diagnostics13243659] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Revised: 12/04/2023] [Accepted: 12/06/2023] [Indexed: 12/23/2023] Open
Abstract
Malignant focal liver lesions (FLLs) represent various kinds of epithelial and mesenchymal tumors. In pediatric patients, the understanding of pediatric liver diseases and associated imaging manifestations is essential for making accurate diagnosis and differential diagnosis. This paper will discuss the latest knowledge of the common pediatric malignant FLLs, including undifferentiated embryonal sarcoma, rhabdomyosarcoma, epithelioid hemangioendothelioma, angiosarcoma, and malignant rhabdoid tumor. Medical imaging features are not only helpful for clinical diagnosis, but can also be useful in the evaluation and follow-up of pre- and post-treatment. The future perspectives of contrast-enhanced ultrasound (CEUS) enhancement patterns of FLLs in pediatric patients are also mentioned.
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Affiliation(s)
- Yi Dong
- Department of Ultrasound, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, 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, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China; (Y.D.); (S.C.); (J.-Y.C.); (Y.-L.H.); (Y.W.)
| | - Jia-Ying Cao
- Department of Ultrasound, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China; (Y.D.); (S.C.); (J.-Y.C.); (Y.-L.H.); (Y.W.)
| | - Yun-Lin Huang
- Department of Ultrasound, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China; (Y.D.); (S.C.); (J.-Y.C.); (Y.-L.H.); (Y.W.)
| | - Ying Wang
- Department of Ultrasound, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, 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 of Ultrasound, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China; (Y.D.); (S.C.); (J.-Y.C.); (Y.-L.H.); (Y.W.)
- Department Allgemeine Innere Medizin (DAIM), Kliniken Hirslanden Beau Site, Salem und Permanence, 3013 Bern, Switzerland
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3
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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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4
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Aldén J, Baecklund F, Psaros Einberg A, Casswall T, Wessman S, Ericzon BG, Nowak G. Is primary hepatic angiosarcoma in children an indication for liver transplantation?-A single-centre experience and review of the literature. Pediatr Transplant 2021; 25:e14095. [PMID: 34288297 DOI: 10.1111/petr.14095] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Revised: 06/20/2021] [Accepted: 07/08/2021] [Indexed: 12/22/2022]
Abstract
PHA in the paediatric population is an extremely rare and aggressive malignant soft tissue neoplasm, with less than 50 cases published worldwide. The prognosis is dismal. If the tumour is unresectable, one treatment option is LT. In this article, the current available literature is reviewed and additionally, three cases of paediatric patients with PHA who underwent LT at Karolinska University Hospital, Sweden, are presented. Based on the literature and our own experience, there is undoubtedly possible good outcome of LT due to PHA. On the contrary, no patients have survived PHA without LT. PHA in paediatric patients should be recommended to LT in selected patients. Effect of modern adjuvant chemo and RT should be evaluated further based on international registry for such rare cases of PHA.
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Affiliation(s)
- Josefin Aldén
- Department of Transplantation Surgery, Karolinska University Hospital Huddinge, Stockholm, Sweden
| | - Fredrik Baecklund
- Paediatric Oncology Unit, Karolinska University Hospital Solna, Stockholm, Sweden
| | - Afrodite Psaros Einberg
- Department of Paediatric Gastroenterology, Hepatology and Nutrition, Karolinska University Hospital Huddinge, Stockholm, Sweden
| | - Thomas Casswall
- Department of Paediatric Gastroenterology, Hepatology and Nutrition, Karolinska University Hospital Huddinge, Stockholm, Sweden
| | - Sandra Wessman
- Department of Clinical Pathology and Cytology, Karolinska University Hospital Solna, Stockholm, Sweden
| | - Bo-Göran Ericzon
- Department of Transplantation Surgery, Karolinska University Hospital Huddinge, Stockholm, Sweden
| | - Greg Nowak
- Department of Transplantation Surgery, Karolinska University Hospital Huddinge, Stockholm, Sweden
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5
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Lang SA, Bednarsch J, Czigany Z, Joechle K, Kroh A, Amygdalos I, Strnad P, Bruns T, Heise D, Ulmer F, Neumann UP. Liver transplantation in malignant disease. World J Clin Oncol 2021; 12:623-645. [PMID: 34513597 PMCID: PMC8394155 DOI: 10.5306/wjco.v12.i8.623] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 06/15/2021] [Accepted: 07/23/2021] [Indexed: 02/06/2023] Open
Abstract
Liver transplantation for malignant disease has gained increasing attention as part of transplant oncology. Following the implementation of the Milan criteria, hepatocellular carcinoma (HCC) was the first generally accepted indication for transplantation in patients with cancer. Subsequently, more liberal criteria for HCC have been developed, and research on this topic is still ongoing. The evident success of liver transplantation for HCC has led to the attempt to extend its indication to other malignancies. Regarding perihilar cholangiocarcinoma, more and more evidence supports the use of liver transplantation, especially after neoadjuvant therapy. In addition, some data also show a benefit for selected patients with very early stage intrahepatic cholangiocarcinoma. Hepatic epithelioid hemangioendothelioma is a very rare but nonetheless established indication for liver transplantation in primary liver cancer. In contrast, patients with hepatic angiosarcoma are currently not considered to be optimal candidates. In secondary liver tumors, neuroendocrine cancer liver metastases are an accepted but comparability rare indication for liver transplantation. Recently, some evidence has been published supporting the use of liver transplantation even for colorectal liver metastases. This review summarizes the current evidence for liver transplantation for primary and secondary liver cancer.
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Affiliation(s)
- Sven Arke Lang
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Jan Bednarsch
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Zoltan Czigany
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Katharina Joechle
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Andreas Kroh
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Iakovos Amygdalos
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Pavel Strnad
- Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Tony Bruns
- Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Daniel Heise
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Florian Ulmer
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Ulf Peter Neumann
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen 52074, Germany
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6
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Lucas B, Ravishankar S, Pateva I. Pediatric Primary Hepatic Tumors: Diagnostic Considerations. Diagnostics (Basel) 2021; 11:333. [PMID: 33670452 PMCID: PMC7922091 DOI: 10.3390/diagnostics11020333] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Revised: 02/12/2021] [Accepted: 02/15/2021] [Indexed: 02/06/2023] Open
Abstract
The liver is the third most common site of abdominal tumors in children. This review article aims to summarize current evidence surrounding identification and diagnosis of primary hepatic tumors in the pediatric population based upon clinical presentation, epidemiology, and risk factors as well as classical imaging, histopathological, and molecular diagnostic findings. Readers will be able to recognize the features and distinguish between benign and malignant hepatic tumors within different age groups.
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Affiliation(s)
- Bryony Lucas
- Rainbow Babies and Children’s Hospital—Department of Pediatrics, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA
| | - Sanjita Ravishankar
- Rainbow Babies and Children’s Hospital—Department of Pathology, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA
| | - Irina Pateva
- Rainbow Babies and Children’s Hospital—Department of Pediatric Hematology and Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA
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7
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Sindhi R, Rohan V, Bukowinski A, Tadros S, de Ville de Goyet J, Rapkin L, Ranganathan S. Liver Transplantation for Pediatric Liver Cancer. Cancers (Basel) 2020; 12:cancers12030720. [PMID: 32204368 PMCID: PMC7140094 DOI: 10.3390/cancers12030720] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2020] [Revised: 03/10/2020] [Accepted: 03/12/2020] [Indexed: 02/06/2023] Open
Abstract
Unresectable hepatocellular carcinoma (HCC) was first removed successfully with total hepatectomy and liver transplantation (LT) in a child over five decades ago. Since then, children with unresectable liver cancer have benefitted greatly from LT and a confluence of several equally important endeavors. Regional and trans-continental collaborations have accelerated the development and standardization of chemotherapy regimens, which provide disease control to enable LT, and also serve as a test of unresectability. In the process, tumor histology, imaging protocols, and tumor staging have also matured to better assess response and LT candidacy. Significant trends include a steady increase in the incidence of and use of LT for hepatoblastoma, and a significant improvement in survival after LT for HCC with each decade. Although LT is curative for most unresectable primary liver sarcomas, such as embryonal sarcoma, the malignant rhabdoid tumor appears relapse-prone despite chemotherapy and LT. Pediatric liver tumors remain rare, and diagnostic uncertainty in some settings can potentially delay treatment or lead to the selection of less effective chemotherapy. We review the current knowledge relevant to diagnosis, LT candidacy, and post-transplant outcomes for these tumors, emphasizing recent observations made from large registries or larger series.
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Affiliation(s)
- Rakesh Sindhi
- Hillman Center for Pediatric Transplantation, UPMC-Children’s Hospital of Pittsburgh, Pittsburgh, PA 15224, USA; (A.B.); (S.T.)
- Correspondence: ; Tel.: +1-412-692-7123
| | - Vinayak Rohan
- Medical University of South Carolina, Charleston, SC 29403, USA;
| | - Andrew Bukowinski
- Hillman Center for Pediatric Transplantation, UPMC-Children’s Hospital of Pittsburgh, Pittsburgh, PA 15224, USA; (A.B.); (S.T.)
| | - Sameh Tadros
- Hillman Center for Pediatric Transplantation, UPMC-Children’s Hospital of Pittsburgh, Pittsburgh, PA 15224, USA; (A.B.); (S.T.)
| | - Jean de Ville de Goyet
- Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), 90127 Palermo, Italy;
| | - Louis Rapkin
- Department of Hematology/Oncology, UPMC-Children’s Hospital of Pittsburgh, Pittsburgh, PA 15224, USA;
| | - Sarangarajan Ranganathan
- Department of Pathology, Children’s Hospital Medical Center of Cincinnati, Cincinnati, OH 45229, USA;
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8
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Pilbeam K, Eidenschink B, Sulciner M, Luquette M, Neglia J, Chinnakotla S. Success of chemotherapy and a liver transplant in a pediatric patient with hepatic angiosarcoma: A case report. Pediatr Transplant 2019; 23:e13410. [PMID: 31012199 DOI: 10.1111/petr.13410] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2018] [Revised: 10/31/2018] [Accepted: 11/06/2018] [Indexed: 12/14/2022]
Abstract
Hepatic angiosarcoma is an extremely rare diagnosis in children, with fewer than 50 pediatric cases reported in the literature worldwide. This aggressive vascular sarcoma carries a very dismal prognosis and is known to be resistant to radiation, chemotherapy, and other vascular-targeted agents. Complete surgical resection is felt to provide the best chance for long-term survival. In patients with tumors not amenable to resection, a liver transplant can be considered. However, very few such transplants have been reported, given that they remain controversial due to high cancer recurrence and mortality post-transplant. Herein, we report the unique case of a 2-year-old child with localized hepatic angiosarcoma not amendable to resection who successfully underwent a liver transplant and received chemotherapy with six cycles of doxorubicin, docetaxel, and ifosfamide.
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Affiliation(s)
- Kristy Pilbeam
- Department of Hematology/Oncology, Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, Indiana
| | | | - Megan Sulciner
- University of Minnesota Medical School, Minneapolis, Minnesota
| | - Mark Luquette
- Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota
| | - Joseph Neglia
- University of Minnesota Masonic Children's Hospital, University of Minnesota, Minneapolis, Minnesota
| | - Srinath Chinnakotla
- Liver Transplant Program, University of Minnesota Masonic Children's Hospital, University of Minnesota, Minneapolis, Minnesota
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9
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Abstract
Although liver tumors are rare in the pediatric population, they are common in the setting of children with specific risk factors requiring increased awareness and, in some instances, screening. The evaluation of a liver mass in children is largely driven by the age at diagnosis, the presence of any medical comorbidities, and initial testing with alpha fetoprotein and imaging. Specific guidelines for the management of different tumors have been implemented in recent years such that a multidisciplinary approach is ideal and care should be provided by centers with experience in their management.
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Affiliation(s)
- Kenneth Ng
- Department of Pediatrics, Johns Hopkins School of Medicine, 600 North Wolfe Street, CMSC 2-117, Baltimore, MD 21287, USA
| | - Douglas B Mogul
- Department of Pediatrics, Johns Hopkins School of Medicine, 600 North Wolfe Street, CMSC 2-117, Baltimore, MD 21287, USA.
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10
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Masand PM. Magnetic resonance imaging features of common focal liver lesions in children. Pediatr Radiol 2018; 48:1234-1244. [PMID: 30078045 DOI: 10.1007/s00247-018-4218-5] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2018] [Revised: 07/06/2018] [Accepted: 07/17/2018] [Indexed: 12/29/2022]
Abstract
Magnetic resonance imaging (MRI) is commonly used to characterize focal liver masses in the pediatric population. MRI is the preferred modality because of its superior contrast resolution and utility for obtaining functional sequences such as diffusion-weighted imaging (DWI). MR exams performed with a hepatocyte-specific gadolinium-based contrast agent can characterize focal liver lesions, which helps in differentiating a common benign entity such as focal nodular hyperplasia from other liver pathology when the background liver is normal. The most common benign focal lesion is a hemangioma, and metastases followed by hepatoblastoma are the most common malignant lesions. This article can help radiologists become familiar with the pre- and post-contrast imaging features of common pediatric liver masses.
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Affiliation(s)
- Prakash M Masand
- Cardiovascular Imaging, Department of Pediatric Radiology, Texas Children's Hospital, 6701 Fannin St., Houston, TX, 77030, USA. .,Baylor College of Medicine, Houston, TX, USA.
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11
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Tran Minh M, Mazzola A, Perdigao F, Charlotte F, Rousseau G, Conti F. Primary hepatic angiosarcoma and liver transplantation: Radiological, surgical, histological findings and clinical outcome. Clin Res Hepatol Gastroenterol 2018; 42:17-23. [PMID: 28416360 DOI: 10.1016/j.clinre.2017.02.006] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2016] [Accepted: 02/09/2017] [Indexed: 02/04/2023]
Abstract
Angiosarcoma is a rare type of soft tissue sarcoma that accounts for less than 1% of all sarcomas and only 2% of all primary hepatic tumours. Thorotrast, arsenic, and vinyl chloride monomer are frequently listed as occupational exposure risks. The estimated latency is long (10-40 years) in occupational cases and very long (60 years or more) in non-occupational cases. The symptoms and CT-scan appearance of hepatic angiosarcoma (HAS) are non-specific. We present a case of a 65-year-old Caucasian male with history of cryptogenic cirrhosis, low alpha-foetoprotein levels and a single, 4-cm nodule of potential atypical hepatocellular carcinoma (no washout at MRI and CT-scan) in segment VIII. Laparoscopic radiofrequency ablation (a biopsy of the neoplastic lesion was technically impossible) was performed, followed by liver transplantation (LT) 6 months later. High-grade multifocal HAS was found in the explanted liver, with extensive involvement of the venous portal structures. No complications were observed during the postoperative course, and initial immunosuppression included tacrolimus, mycophenolate mofetil and corticosteroids. Because of the histological findings, tacrolimus was switched to everolimus as the main immunosuppressive drug one month after LT. Despite this conversion, the patient developed bone metastases 3 months after LT and peritoneal carcinosis one month later. This case report suggests that everolimus conversion does not inhibit the development of tumour metastases. Consequently, HAS remains an absolute contraindication to LT because of the poor outcome. If LT has been performed for incidental HAS, new molecular therapies (e.g. vascular endothelial growth factor antagonists) should be considered immediately after LT to improve the outcome.
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Affiliation(s)
- M Tran Minh
- Unité Médicale de Transplantation Hépatique, Hôpital Pitié-Salpétrière, AP-HP, 75013 Paris, France; Medicina Traslazionale, Università Piemonte Orientale Amedeo Avogrado, Novara, Italy
| | - A Mazzola
- Unité Médicale de Transplantation Hépatique, Hôpital Pitié-Salpétrière, AP-HP, 75013 Paris, France
| | - F Perdigao
- Service de Chirurgie Hépatobiliaire et Transplantation Hépatique, Hôpital Pitié-Salpétrière, AP-HP, 75013 Paris, France
| | - F Charlotte
- Service d'Anatomie et Cytologie Pathologique, Hôpital Pitié-Salpétrière, AP-HP, 75013 Paris, France
| | - G Rousseau
- Service de Chirurgie Hépatobiliaire et Transplantation Hépatique, Hôpital Pitié-Salpétrière, AP-HP, 75013 Paris, France
| | - F Conti
- Unité Médicale de Transplantation Hépatique, Hôpital Pitié-Salpétrière, AP-HP, 75013 Paris, France; UMR_S 938, CDR Saint-Antoine, Sorbonne Universités, UPMC Université Paris 06, 75005 Paris, France.
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12
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Grassia KL, Peterman CM, Iacobas I, Margolin JF, Bien E, Padhye B, Meyers RL, Adams DM. Clinical case series of pediatric hepatic angiosarcoma. Pediatr Blood Cancer 2017; 64. [PMID: 28521077 DOI: 10.1002/pbc.26627] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2017] [Revised: 04/03/2017] [Accepted: 04/10/2017] [Indexed: 12/11/2022]
Abstract
Hepatic angiosarcoma is a rare, aggressive, malignant neoplasm with fewer than 50 cases reported in children. Prognosis is poor, with a minority surviving beyond 2 years after diagnosis. We report eight cases of pediatric hepatic angiosarcoma, diagnosed at a mean age of 3 years. Seven were initially diagnosed with an infantile hepatic hemangioendothelioma (IHHE) or hemangioma and the eighth with a "vascular tumor." Two patients, who received liver transplant, survived. We suggest hepatic hemangiomas can rarely transform into angiosarcomas and a subset of IHHEs (Type II) are actually a low-grade form of angiosarcoma rather than a benign lesion.
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Affiliation(s)
- Kalee L Grassia
- University of Cincinnati College of Medicine, Cincinnati, Ohio.,Division of Hematology/Oncology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Caitlin M Peterman
- Tufts University School of Medicine, Boston, Massachusetts.,Department of Dermatology, Harvard Medical School, Boston Children's Hospital, Boston, Massachusetts
| | - Ionela Iacobas
- Division of Hematology/Oncology, Baylor College of Medicine, Houston, Texas
| | - Judith F Margolin
- Division of Hematology/Oncology, Baylor College of Medicine, Houston, Texas
| | - Ewa Bien
- Department of Pediatrics, Hematology, and Oncology, Medical University of Gdansk, Gdansk, Poland
| | - Bhavna Padhye
- Department of Oncology, The Children's Hospital at Westmead, Sydney, Australia
| | - Rebecka L Meyers
- Department of Surgery, University of Utah Health Center, Salt Lake City, Utah
| | - Denise M Adams
- Division of Hematology/Oncology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.,Department of Hematology/Oncology, Harvard Medical School, Boston Children's Hospital, Boston, Massachusetts
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13
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Miloh T, Barton A, Wheeler J, Pham Y, Hewitt W, Keegan T, Sanchez C, Bulut P, Goss J. Immunosuppression in pediatric liver transplant recipients: Unique aspects. Liver Transpl 2017; 23:244-256. [PMID: 27874250 DOI: 10.1002/lt.24677] [Citation(s) in RCA: 67] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2016] [Accepted: 11/03/2016] [Indexed: 02/07/2023]
Abstract
Pediatric liver transplantation has experienced improved outcomes over the last 50 years. This can be attributed in part to establishing optimal use of immunosuppressive agents to achieve a balance between minimizing the risks of allograft rejection and infection. The management of immunosuppression in children is generally more complex and can be challenging when compared with the use of these agents in adult liver transplant patients. Physiologic differences in children alter the pharmacokinetics of immunosuppressive agents, which affects absorption, distribution, metabolism, and drug excretion. Children also have a longer expected period of exposure to immunosuppression, which can impact growth, risk of infection (bacterial, viral, and fungal), carcinogenesis, and likelihood of nonadherence. This review discusses immunosuppressive options for pediatric liver transplant recipients and the unique issues that must be addressed when managing this population. Further advances in the field of tolerance and accommodation are needed to relieve the acute and cumulative burden of chronic immunosuppression in children. Liver Transplantation 23 244-256 2017 AASLD.
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Affiliation(s)
- Tamir Miloh
- Texas Children's Hospital and Baylor College of Medicine, Houston, TX
| | - Andrea Barton
- Texas Children's Hospital and Baylor College of Medicine, Houston, TX
| | | | - Yen Pham
- Texas Children's Hospital and Baylor College of Medicine, Houston, TX
| | | | | | | | | | - John Goss
- Texas Children's Hospital and Baylor College of Medicine, Houston, TX
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14
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Millan M, Delgado A, Caicedo LA, Arrunategui AM, Meneses CA, Villegas JI, Serrano O, Caicedo L, Duque M, Echeverri GJ. Liver Angiosarcoma: Rare tumour associated with a poor prognosis, literature review and case report. Int J Surg Case Rep 2016; 28:165-168. [PMID: 27718433 PMCID: PMC5061303 DOI: 10.1016/j.ijscr.2016.09.044] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2016] [Revised: 09/26/2016] [Accepted: 09/27/2016] [Indexed: 12/13/2022] Open
Abstract
Liver Angiosarcoma is rare and aggressive tumour that requires surgical management. Partial Hepatectomy is the ideal surgical management for Liver Angiosarcoma. Liver transplant does not improve the survival of Liver Angiosarcoma patients. Introduction Liver angiosarcoma is a very uncommon tumour of mesenchymal origin, representing between 0.1–2% of all primary tumours of the liver, affecting mainly men in their sixth or seventh decade of life, with a high mortality in the first years (Chaudhary et al., 2015). Literature reports of its surgical treatment vary from a total or partial hepatectomy with or without liver transplant. Presentation of case A 37 year old male, with a 7 year history of a fatty liver, was found to have a 12 cm diameter tumour in a cirrhotic liver, during an abdominal Computed Tomography (CT) scan. Patient was asymptomatic with negative tumour markers, yet tumour liver biopsy revealed a Liver Angiosarcoma with positive immunohistochemistry for neoplastic cells CD31 and CD34. Patient was deemed candidate for a partial hepatectomy of the affected liver segments which was done without complications and no evidence of other tumour lesions was found during surgery. Patient continued oncologic management with ongoing chemotherapy. Discusion Liver Angiosarcoma, although rare, persists with a high mortality due to its aggressive nature. Never the less liver transplantation, although proven to be an effective treatment for many pathologies that culminate in liver failure, fails to improve patients’ survival and prognosis, when compared to partial hepatectomy as surgical management to for liver Angiosarcoma, Conclusion Partial hepatectomy as surgical management, followed by adjuvant therapy, for Liver Angiosarcoma continues to prove favourable results and prognosis compared to Liver Transplantation.
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Affiliation(s)
- Mauricio Millan
- Transplant Surgery Department, Fundación Valle de Lilí, Cali, Colombia; Centro para la Investigación en Cirugía Avanzada y Trasplantes, Universidad ICESI, Cali, Colombia
| | - Alejandro Delgado
- Centro de Investigaciones Clínicas, Fundación Valle del Lilí, Cali, Colombia; Centro para la Investigación en Cirugía Avanzada y Trasplantes, Universidad ICESI, Cali, Colombia
| | - Luis A Caicedo
- Transplant Surgery Department, Fundación Valle de Lilí, Cali, Colombia; Centro para la Investigación en Cirugía Avanzada y Trasplantes, Universidad ICESI, Cali, Colombia
| | | | | | - Jorge I Villegas
- Transplant Surgery Department, Fundación Valle de Lilí, Cali, Colombia; Centro para la Investigación en Cirugía Avanzada y Trasplantes, Universidad ICESI, Cali, Colombia
| | - Oscar Serrano
- Transplant Surgery Department, Fundación Valle de Lilí, Cali, Colombia; Centro para la Investigación en Cirugía Avanzada y Trasplantes, Universidad ICESI, Cali, Colombia
| | - Liliana Caicedo
- Transplant Surgery Department, Fundación Valle de Lilí, Cali, Colombia; Centro para la Investigación en Cirugía Avanzada y Trasplantes, Universidad ICESI, Cali, Colombia
| | - Mauricio Duque
- Transplant Surgery Department, Fundación Valle de Lilí, Cali, Colombia; Centro para la Investigación en Cirugía Avanzada y Trasplantes, Universidad ICESI, Cali, Colombia
| | - Gabriel J Echeverri
- Transplant Surgery Department, Fundación Valle de Lilí, Cali, Colombia; Centro para la Investigación en Cirugía Avanzada y Trasplantes, Universidad ICESI, Cali, Colombia.
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15
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Chaudhary P, Bhadana U, Singh RAK, Ahuja A. Primary hepatic angiosarcoma. Eur J Surg Oncol 2015; 41:1137-43. [PMID: 26008857 DOI: 10.1016/j.ejso.2015.04.022] [Citation(s) in RCA: 75] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2014] [Revised: 04/22/2015] [Accepted: 04/27/2015] [Indexed: 02/07/2023] Open
Abstract
Primary hepatic angiosarcoma is a rare, aggressive tumor; composed of spindle or pleomorphic cells that line, or grow into, the lumina of pre-existing vascular spaces like sinusoids and terminal hepatic venules; with only about 200 cases diagnosed annually worldwide but it is the most common primary malignant mesenchymal tumor of the liver in adults and accounts for 2% of all primary hepatic malignancies. HAS occurs in association with known chemical carcinogens, but 75% of the tumors have no known etiology. Patients present with vague symptoms like abdominal pain, weight loss, fatigue or an abdominal mass. Hepatic angiosarcoma is usually multicentric and involves both lobes, entire liver may also found to be involved. CD31 is the most reliable marker. These tumors lack specific features on imaging, so, pathological diagnosis is necessary. There are no established treatment guidelines because of low frequency and aggressive nature of tumor, chemotherapy is only palliative, liver resection is indicated for solitary mass and liver transplant is contraindicated. The aim of this article is to comprehensively review all the available literature and to present detailed information and an update on primary hepatic angiosarcoma.
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Affiliation(s)
- P Chaudhary
- Lady Hardinge Medical College and Associated Dr Ram Manohar Lohia Hospital, New Delhi, India.
| | - U Bhadana
- Lady Hardinge Medical College and Associated Dr Ram Manohar Lohia Hospital, New Delhi, India
| | - R A K Singh
- Dr Ram Manohar Lohia Hospital, New Delhi, India
| | - A Ahuja
- Department of Pathology, Dr Ram Manohar Lohia Hospital, New Delhi, India
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16
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Yoon HS, Choi YS, Im HJ. Hepatic angiosarcoma mimicking congenital cytomegalovirus infection in an infant with thrombocytopenia. Pediatr Int 2015; 57:e81-3. [PMID: 25711970 DOI: 10.1111/ped.12558] [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: 05/15/2014] [Revised: 07/24/2014] [Accepted: 10/01/2014] [Indexed: 11/28/2022]
Abstract
Hepatic angiosarcomas are uncommon, highly aggressive tumors, rarely seen in children. A 3-month-old female infant was admitted to hospital for evaluation of multiple petechiae on her body. She had hepatosplenomegaly and scattered petechiae over her entire body. Laboratory tests indicated thrombocytopenia and positive cytomegalovirus (CMV) polymerase chain reaction. Ganciclovir was started, and the platelet count increased. After 4 months the patient was readmitted to hospital for drowsy mental status and eventually died from severe bleeding. Needle biopsy of the liver was performed after receiving written consent from the parents. Pathological findings of the liver lesion included features consistent with hepatic angiosarcoma. There have been no previous reports of hepatic angiosarcoma in Korean infants. Here, we report an infant with hepatosplenomegaly and thrombocytopenia who was diagnosed with hepatic angiosarcoma mimicking congenital CMV infection.
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Affiliation(s)
- Hoi Soo Yoon
- Department of Pediatrics, Kyung Hee University Medical Center, Seoul, Korea
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