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Dasari BVM, Line PD, Sapisochin G, Hibi T, Bhangui P, Halazun KJ, Shetty S, Shah T, Magyar CTJ, Donnelly C, Chatterjee D. Liver transplantation as a treatment for cancer: comprehensive review. BJS Open 2025; 9:zraf034. [PMID: 40380811 PMCID: PMC12084677 DOI: 10.1093/bjsopen/zraf034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2024] [Revised: 01/30/2025] [Accepted: 02/07/2025] [Indexed: 05/19/2025] Open
Abstract
BACKGROUND Liver transplantation for cancer indications has gained momentum in recent years. This review is intended to optimize the care setting of liver transplant candidates by highlighting current indications, technical aspects and barriers with available solutions to facilitate the guidance of available strategies for healthcare professionals in specialized centres. METHODS A review of the most recent relevant literature was conducted for all the cancer indications of liver transplantation including colorectal cancer liver metastases, hilar cholangiocarcinoma, intrahepatic cholangiocarcinoma, neuroendocrine tumours, hepatocellular carcinoma and hepatic epitheloid haemangioendothelioma. RESULTS Transplant benefit from the best available evidence, including SECA I, SECA II, TRANSMET studies for colorectal liver metastases, various preoperative protocols for cholangiocarcinoma patients, standard, extended selection criteria for hepatocellular carcinoma and neuroendocrine tumours, are discussed. Innovative approaches to deal with organ shortages, including machine-perfused deceased grafts, living donor liver transplantation and RAPID procedures, are also explored. CONCLUSION Cancer indications for liver transplantation are here to stay, and the selection criteria among all cancer groups are likely to evolve further with improved prognostication of tumour biology using adjuncts such as radiomics, cancer genomics, and circulating DNA and RNA status. International prospective registry-based studies could overcome the limitations of smaller patient cohorts and lack of level 1 evidence.
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Affiliation(s)
- Bobby V M Dasari
- Department of Liver Transplantation and HBP Surgery, Queen Elizabeth Hospital, Birmingham, UK
- Department of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
| | - Pal-Dag Line
- Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway
| | - Gonzalo Sapisochin
- Department of Surgery, Multi-Organ Transplant Program, University Health Network, Toronto, Canada
| | - Taizo Hibi
- Department of Pediatric Surgery and Transplantation, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
| | - Prashant Bhangui
- Liver Transplantation and Hepatobiliary Surgery, Medanta Institute of Liver Transplantation and Regenerative Medicine, Medanta-The Medicity, Gurgaon (Delhi NCR), India
| | - Karim J Halazun
- Department of Liver Transplantation and Hepatobiliary Surgery, NYU Grossman School of Medicine, NYU Langone Health, New York, USA
| | - Shishir Shetty
- Department of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
- Department of Hepatology, Queen Elizabeth Hospital, Birmingham, UK
| | - Tahir Shah
- Department of Hepatology, Queen Elizabeth Hospital, Birmingham, UK
| | - Christian T J Magyar
- Department of Abdominal Transplant & HBP Surgical Oncology, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Canada
| | - Conor Donnelly
- Department of Liver Transplantation and Hepatobiliary Surgery, NYU Grossman School of Medicine, NYU Langone Health, New York, USA
| | - Dev Chatterjee
- BRC Clinical Fellow Liver Medicine, University Hospitals of Birmingham, Birmingham, UK
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Wang B, Chen X, Li R, Ai B, Ye F, Zhao J, Zhang Y, Huang Z, Li Z, Bi X, Zhao H, Cao D, Cai J, Zhou J, Yan T. Comprehensive evaluation of clinical outcomes in hepatic epithelioid hemangioendothelioma subsets: insights from SEER Database and departmental cohort analysis. Front Immunol 2024; 15:1491922. [PMID: 39502705 PMCID: PMC11534872 DOI: 10.3389/fimmu.2024.1491922] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Accepted: 10/07/2024] [Indexed: 11/08/2024] Open
Abstract
Background Epithelioid hemangioendothelioma (EHE), is an uncommon, intermediate-grade malignant vascular tumor that can manifest in diverse organs, including the liver, lungs, and bones. Given its unique malignancy profile and rarity, there lacks a consensus on a standardized treatment protocol for EHE, particularly for hepatic epithelioid hemangioendothelioma (HEHE). This study aims to elucidate factors influencing the clinical prognosis of EHE by analyzing data from the SEER database, complemented with insights from a departmental cohort of 9 HEHE cases. Through this, we hope to shed light on potential clinical outcomes and therapeutic strategies for HEHE. Methods Using SEER data from 22 registries, we analyzed 313 liver cancer patients with ICD-O-3 9130 and 9133 histology. Twelve variables were examined using Cox regression and mlr3 machine learning. Significant variables were identified and compared. Clinical data, imaging characteristics, and treatment methods of nine patients from our cohort were also presented. Result In univariate and multivariate Cox regression analyses, Age, Sex, Year of diagnosis, Surgery of primary site, Chemotherapy, and Median household income were closely related to survival outcomes. Among the ten survival-related machine learning models, CoxPH, Flexible, Mboost, and Gamboost stood out based on Area Under the Curve(AUC), Decision Curve Analysis(DCA), and Calibration Curve Metrics. In the feature importance analysis of these four selected models, Age and Surgery of primary site were consistently identified as the most critical factors influencing prognosis. Additionally, the clinical data of nine patients from our cohort not only demonstrated unique imaging characteristics of HEHE but also underscored the importance of surgical intervention. Conclusion For patients with resectable HEHE, surgical treatment is currently a highly important therapeutic approach.
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Affiliation(s)
- Bingchen Wang
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiao Chen
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Rongxuan Li
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Bolun Ai
- Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Feng Ye
- Department of Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jianjun Zhao
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yefan Zhang
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhen Huang
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhiyu Li
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xinyu Bi
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hong Zhao
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Dayong Cao
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jianqiang Cai
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jianguo Zhou
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Tao Yan
- Department of Anesthesiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Sawma T, Sultan A, Abdulmoneim S, Grotz T, Rosen CB, Taner T, Heimbach JK, Warner SG, Siontis BL, Ho TP, Robinson SI, Thiels CA. Management and Long-Term Outcomes of Patients With Hepatic Epithelioid Hemangioendothelioma. J Surg Oncol 2024; 130:1062-1069. [PMID: 39318157 DOI: 10.1002/jso.27807] [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: 07/13/2024] [Accepted: 07/26/2024] [Indexed: 09/26/2024]
Abstract
BACKGROUND AND OBJECTIVES Hepatic epithelioid hemangioendothelioma (HEHE) is an uncommon vascular neoplasm characterized by variable clinical behavior. Our aim was to describe the therapeutic approach for HEHE at diagnosis and define clinicopathological characteristics associated with tumor progression and long-term survival. METHODS This is a retrospective study that includes patients with HEHE who received treatment at Mayo Clinic Rochester between 1984 and 2023. RESULTS Eighty patients were included in the study (median age: 44 years; 62.5% female), 24 underwent liver transplantation, 26 underwent liver resection, and 30 were managed medically. The 3-year overall survival rates were 86.7%, 80.9%, and 51.1%, respectively. Notably, 26 patients had extrahepatic metastases at the time of diagnosis, four (16.7%) in the transplantation group, four (15.4%) in the resection group, and 18 (69.2%) in the nonsurgical group. On multivariable modeling, bone metastasis was independently associated with long-term mortality (HR 6.3, p < 0.001) while lung metastasis and surgical intervention were not associated with long-term mortality (HR 0.8, p = 0.8; HR 1.1, p = 0.9, respectively). CONCLUSION Bone metastasis emerged as a strong predictor of poor survival. Hence, aggressive surgical intervention may not be advantageous in patients with skeletal metastases but can still be offered for those with other extrahepatic metastases.
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Affiliation(s)
- Tedy Sawma
- Division of Hepatobiliary & Pancreas Surgery, Mayo Clinic, Rochester, Minnesota, USA
| | - Ahmer Sultan
- Division of Hepatobiliary & Pancreas Surgery, Mayo Clinic, Rochester, Minnesota, USA
| | - Samer Abdulmoneim
- Division of Hepatobiliary & Pancreas Surgery, Mayo Clinic, Rochester, Minnesota, USA
| | - Travis Grotz
- Division of Hepatobiliary & Pancreas Surgery, Mayo Clinic, Rochester, Minnesota, USA
| | - Charles B Rosen
- Division of Transplantation Surgery, Mayo Clinic, Rochester, Minnesota, USA
| | - Timucin Taner
- Division of Transplantation Surgery, Mayo Clinic, Rochester, Minnesota, USA
| | - Julie K Heimbach
- Division of Transplantation Surgery, Mayo Clinic, Rochester, Minnesota, USA
| | - Susanne G Warner
- Division of Hepatobiliary & Pancreas Surgery, Mayo Clinic, Rochester, Minnesota, USA
| | | | - Thanh P Ho
- Department of Medical Oncology, Mayo Clinic, Rochester, Minnesota, USA
| | - Steven I Robinson
- Department of Medical Oncology, Mayo Clinic, Rochester, Minnesota, USA
| | - Cornelius A Thiels
- Division of Hepatobiliary & Pancreas Surgery, Mayo Clinic, Rochester, Minnesota, USA
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Melehy A, Agopian V. Treating rare tumors with liver transplantation. Curr Opin Organ Transplant 2024; 29:30-36. [PMID: 37851086 DOI: 10.1097/mot.0000000000001118] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2023]
Abstract
PURPOSE OF REVIEW The success of liver transplantation (LT) in treating unresectable hepatocellular carcinoma (HCC) has resulted in interest in LT for other oncologic conditions. Here, we discuss the role of LT for rare oncologic indications including metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs), hepatic epitheliod hemangioendothelioma (HEHE), fibrolamellar hepatocellular carcinoma (FLC), and hepatic angiosarcoma (HAS). RECENT FINDINGS Conditions reviewed have been documented indications for LT in the available literature. We summarize the experience of LT for these indications and proposed management guidelines. SUMMARY GEP-NETs with isolated metastases to the liver can be treated with LT with excellent long-term outcomes (10-year survival 88%) if strict selection criteria are used (low-intermediate grade, Ki-67% < 20%, complete resection of primary tumor, stable disease for 6 months, <50% hepatic involvement). HEHE is a rare hepatic tumor for which LT can be performed with reported 10-year survival around 70%. FLC is a distinct clinical entity to HCC and is optimally treated with surgical resection though experience with LT is described in observational series (5-year survival 50%, recurrence in 10%). HAS is a rapidly progressive tumor with a dismal prognosis with or without treatment, including LT.
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Affiliation(s)
- Andrew Melehy
- Dumont-UCLA Transplant and Liver Cancer Centers, Department of Surgery, David Geffen School of Medicine at University of California, Los Angeles, California, USA
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Krendl FJ, Bellotti R, Sapisochin G, Schaefer B, Tilg H, Scheidl S, Margreiter C, Schneeberger S, Oberhuber R, Maglione M. Transplant oncology - Current indications and strategies to advance the field. JHEP Rep 2024; 6:100965. [PMID: 38304238 PMCID: PMC10832300 DOI: 10.1016/j.jhepr.2023.100965] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Revised: 10/31/2023] [Accepted: 11/04/2023] [Indexed: 02/03/2024] Open
Abstract
Liver transplantation (LT) was originally described by Starzl as a promising strategy to treat primary malignancies of the liver. Confronted with high recurrence rates, indications drifted towards non-oncologic liver diseases with LT finally evolving from a high-risk surgery to an almost routine surgical procedure. Continuously improving outcomes following LT and evolving oncological treatment strategies have driven renewed interest in transplant oncology. This is not only reflected by constant refinements to the criteria for LT in patients with HCC, but especially by efforts to expand indications to other primary and secondary liver malignancies. With new patient-centred oncological treatments on the rise and new technologies to expand the donor pool, the field has the chance to come full circle. In this review, we focus on the concept of transplant oncology, current indications, as well as technical and ethical aspects in the context of donor organs as precious resources.
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Affiliation(s)
- Felix J. Krendl
- Department of Visceral, Transplant and Thoracic Surgery, Center for Operative Medicine, Medical University of Innsbruck, Austria
| | - Ruben Bellotti
- Department of Visceral, Transplant and Thoracic Surgery, Center for Operative Medicine, Medical University of Innsbruck, Austria
| | - Gonzalo Sapisochin
- Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
| | - Benedikt Schaefer
- Department of Medicine I, Gastroenterology, Hepatology and Endocrinology, Medical University of Innsbruck, Austria
| | - Herbert Tilg
- Department of Medicine I, Gastroenterology, Hepatology and Endocrinology, Medical University of Innsbruck, Austria
| | - Stefan Scheidl
- Department of Visceral, Transplant and Thoracic Surgery, Center for Operative Medicine, Medical University of Innsbruck, Austria
| | - Christian Margreiter
- Department of Visceral, Transplant and Thoracic Surgery, Center for Operative Medicine, Medical University of Innsbruck, Austria
| | - Stefan Schneeberger
- Department of Visceral, Transplant and Thoracic Surgery, Center for Operative Medicine, Medical University of Innsbruck, Austria
| | - Rupert Oberhuber
- Department of Visceral, Transplant and Thoracic Surgery, Center for Operative Medicine, Medical University of Innsbruck, Austria
| | - Manuel Maglione
- Department of Visceral, Transplant and Thoracic Surgery, Center for Operative Medicine, Medical University of Innsbruck, Austria
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Feng L, Li M, Huang Z, Xu M. Hepatic epithelioid hemangioendothelioma-a single-institution experience with 51 cases. Front Oncol 2023; 13:1236134. [PMID: 37601682 PMCID: PMC10435877 DOI: 10.3389/fonc.2023.1236134] [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: 06/07/2023] [Accepted: 07/17/2023] [Indexed: 08/22/2023] Open
Abstract
Objectives The aim of the present study was to describe the experience at a single institution in the management of hepatic epithelioid hemangioendothelioma (HEHE). Methods We included 51 patients with histologically confirmed HEHE. We performed log-rank (Cox-Mantel) survival analyses using Kaplan-Meier methods to test differences in survival between patients in different groups. Univariate Cox regression analyses and multivariate proportional hazards regression model were carried out to identify independent prognostic factors. Results Different imaging modalities were used to diagnose HEHE with various presentations. Liver resection (LR), liver transplantation (LT), systemic treatment (ST), and surveillance had been used in our study. A significant difference was noted between the LR group and the surveillance group with respect to mean survival (p = 0.006), as was in the LR group and the ST group (p = 0.036), and in surgical approach (LR and LT) and nonsurgical approach (ST and surveillance) (p = 0.008). The mean survival between the ST group and the surveillance group was not significantly different (p = 0.851). LR (p = 0.010) and surgical approach (p = 0.014) were favorable predictors of outcome, while macrovascular invasion (MaVI) (p = 0.037), lung metastasis (p = 0.040), and surveillance (p = 0.033) were poor prognostic factors in univariate analysis. Multivariate analysis showed that LR (p = 0.010) and surgical approach (p = 0.014) were independently associated with good OS, while surveillance (p = 0.033) was independently associated with poor OS. After adjusting for confounding factors, patients in the LR group have much better OS than those in the surveillance group (p = 0.013). However, there was no significant difference in OS between the LR group and ST group (p = 0.254), as was in the ST group and the surveillance group (p = 0.857). Conclusions The definitive diagnosis of HEHE was dependent on histopathology, and it was not possible to make a specific diagnosis without biopsy because the radiological findings were similar to those in some hepatic malignancies. ST was not recommended for patients who were not candidates for surgical approaches, and surgical approaches should be warranted regardless of disease stage. The retrospective nature and the small size of the data limited the generalizability of the study, designing a worldwide database that contains all data about patients with HEHE independent of their therapy, which was highly recommended.
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Affiliation(s)
- Lei Feng
- Division of Biliary Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Manjie Li
- Radiology Department of West China Tianfu Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Zhuo Huang
- Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Mingqing Xu
- Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
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Dobrindt EM, Öllinger R, Flörcken A, Märdian S, Schmelzle M, Lurje G, Pratschke J, Schoening W. [Primary Hepatic Sarcoma - Recommendations for Therapy]. Zentralbl Chir 2023; 148:165-179. [PMID: 35211924 DOI: 10.1055/a-1728-6939] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Eva Maria Dobrindt
- Klinik für Chirurgie, Charité - Universitätsmedizin Berlin, Berlin, Deutschland
| | - Robert Öllinger
- Klinik für Chirurgie, Charité - Universitätsmedizin Berlin, Berlin, Deutschland
| | - Anne Flörcken
- Medizinische Klinik m.S. Hämatologie, Onkologie und Tumorimmunologie, Charité - Universitätsmedizin Berlin, Berlin, Deutschland
| | - Sven Märdian
- Zentrum für Muskuloskeletale Chirurgie, Charité - Universitätsmedizin Berlin, Berlin, Deutschland
| | - Moritz Schmelzle
- Klinik für Chirurgie, Charité - Universitätsmedizin Berlin, Berlin, Deutschland
| | - Georg Lurje
- Klinik für Chirurgie, Charité - Universitätsmedizin Berlin, Berlin, Deutschland
| | - Johann Pratschke
- Klinik für Chirurgie, Charité - Universitätsmedizin Berlin, Berlin, Deutschland
| | - Wenzel Schoening
- Klinik für Chirurgie, Charité - Universitätsmedizin Berlin, Berlin, Deutschland
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Ajay PS, Tsagkalidis V, Casabianca A, Burchard PR, Melucci AD, Chacon A, Goyal S, Switchenko JM, Kooby DA, Carpizo DR, Shah MM. A review of hepatic epithelioid hemangioendothelioma-Analyzing patient characteristics and treatment strategies. J Surg Oncol 2022; 126:1423-1429. [PMID: 35975699 PMCID: PMC9836828 DOI: 10.1002/jso.27066] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Accepted: 07/30/2022] [Indexed: 01/14/2023]
Abstract
BACKGROUND Hepatic epithelioid hemangioendothelioma (HEH) is a rare vascular tumor of unknown etiology and unpredictable natural history. To date, no large-scale studies have been published evaluating this disease due to its rare occurrence. METHODS The National Cancer Database was reviewed between 2004 and 2016 to identify patients with HEH. Univariate analysis with overall survival (OS) was performed by Cox proportional hazards model. Kaplan-Meier method was used to create OS curves and compared using the log-rank test. RESULTS We identified 229 patients with HEH. The majority of patients were female (61.1%), white (84.3%), and had a Charlson-Deyo score of 0 (75%). Chemotherapeutic intervention was seen in 26% of the patients while 33% received surgical intervention in the form of wedge/segmental liver resection (n = 27), hepatectomy lobectomy/extended lobectomy (n = 18), and liver transplant (n = 22). Five-year survival in surgical patients was 90.5%, 66.5% and 81%, respectively (p = 0.485). Age greater than 55 years (hazard ratio [HR], 2.78; p < 0.001), Asian ethnicity compared to white (HR, 2.84; p = 0.012), and a higher Charlson-Deyo score (score 1: HR, 2.28; p < 0.001 and score ≥2: HR, 2.76; p = 0.011) were associated with worse OS. CONCLUSION Treatment for HEH remains variable with only a third of the patients undergoing surgery. International collaboration is necessary to determine the optimal treatment for this rare disease.
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Affiliation(s)
- Pranay S. Ajay
- Division of Surgical Oncology, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Vasileios Tsagkalidis
- Department of Surgery, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA
| | - Anthony Casabianca
- Department of Surgery, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA
| | - Paul R. Burchard
- Department of Surgery, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA
| | - Alexa D. Melucci
- Department of Surgery, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA
| | - Alexander Chacon
- Department of Surgery, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA
| | - Subir Goyal
- Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA
| | - Jeffrey M. Switchenko
- Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA
| | - David A. Kooby
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Darren R. Carpizo
- Division of Surgical Oncology, Wilmot Caner Center, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA
| | - Mihir M. Shah
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia, USA
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Chu K, Li Z, Tang W, Jiang X. Updated information regarding management of hepatic epithelioid hemangioendothelioma. Intractable Rare Dis Res 2022; 11:211-214. [PMID: 36457586 PMCID: PMC9709622 DOI: 10.5582/irdr.2022.01113] [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: 10/12/2022] [Revised: 11/04/2022] [Accepted: 11/06/2022] [Indexed: 11/10/2022] Open
Abstract
Hepatic epithelioid hemangioendothelioma (HEHE) is a rare hepatic vascular tumor with a borderline biological behavior between hemangioma and hemangiosarcoma. It tends to be multiple or diffuse subcapsular lesions across the liver but has no characteristic clinical manifestations or imaging findings. On computed tomography and magnetic resonance imaging, these lesions usually have a hypodense appearance with heterogeneous enhancement and a "halo sign" or "lollipop sign" may be evident in some cases. HEHE is diagnosed mainly based on a pathological examination along with differential immunohistochemical markers such as CAMTA1, CD31, CD34, CD10, vimentin, and factor VIII antigen. Currently, there are no standardized treatment guidelines for HEHE, and surgery (curative resection and liver transplantation) remains the mainstay of treatment. Studies have indicated that extra-hepatic metastasis might not be a contraindication for resection or transplantation. Systemic chemotherapeutic agents including doxorubicin, vincristine, interferon-a, 5-fluorouracil, and thalidomide, as well as VEGF-related agents are being investigated, but no agents have been approved for the treatment of HEHE.
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Affiliation(s)
- Kaijian Chu
- Biliary Surgery Department No. 1, Eastern Hepatobiliary Surgical Hospital, Naval Medical University, Shanghai, China
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Zhizheng Li
- Biliary Surgery Department No. 1, Eastern Hepatobiliary Surgical Hospital, Naval Medical University, Shanghai, China
| | - Wei Tang
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
- International Health Care Center, National Center for Global Health and Medicine, Tokyo, Japan
| | - Xiaoqing Jiang
- Biliary Surgery Department No. 1, Eastern Hepatobiliary Surgical Hospital, Naval Medical University, Shanghai, China
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Epithelioid Hemangioendothelioma: Incidence, Mortality, Prognostic Factors, and Survival Analysis Using the Surveillance, Epidemiology, and End Results Database. JOURNAL OF ONCOLOGY 2022; 2022:2349991. [PMID: 36157226 PMCID: PMC9507694 DOI: 10.1155/2022/2349991] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Revised: 09/02/2022] [Accepted: 09/06/2022] [Indexed: 12/04/2022]
Abstract
Background Although epithelioid hemangioendothelioma (EHE) is a rare and aggressive vascular tumor, its demographic characteristics remain unclear. We used the surveillance, epidemiology, and end results (SEER) database to determine the clinical features, incidence, and prognostic factors associated with overall survival in patients with EHE. Methods The demographic and clinical data of patients with EHE were extracted from the SEER database (1975-2019) to calculate the incidence of EHE and survival rate in these patients. The Cox proportional hazards model and Kaplan-Meier method were used to analyze the prognostic factors of overall survival in these patients. A nomogram and time-dependent receiver operating characteristic (ROC) curve were employed to predict the 3- and 5-year survival rate. Results The overall incidence rate (IR) of EHE was 0.230 (95%confidence interval [CI] = 0.201–0.263) per 1,000,000 person-years. According to the age-stratified IR, the highest age-adjusted IR was observed in patients aged 60–79 years (0.524 per 1,000,000 person-years, 95%CI = 0.406–0.665). The majority (30.8%) of the tumors were located in the soft tissue and skin, followed by lesions in the abdomen (28%), respiratory system (19%), bone and joint (8.6%), and others. The 5-year overall survival rate was 55.6% (95%CI = 32.8–73.5%). Multiple Cox regression analysis revealed that age >80 years (hazard ratio [HR] = 8.57, 95%CI = 2.32–31.63, P < 0.001), African-American race (HR = 2.52, 95%CI = 1.31–4.85, P < 0.01), “American Indian/Alaska Native” or “Asian or Pacific Islander” (HR = 2.99, 95%CI = 1.5–5.96, P < 0.01) race, and respiratory tumors (HR = 2.55, 95%CI = 1.37–4.75, P < 0.01) were distinctly related to worse overall survival. The calibration plots demonstrated good consistency between nomogram-predicted and actual survival. The area under the time-dependent ROC curve was 0.721 (95%CI = 0.63–0.81) and 0.719 (95%CI = 0.63–0.81) for the 3- and 5-year survival, respectively. For the convenience of researchers and clinicians, we designed an online dynamics nomogram to predict the survival rate. Conclusion EHE is a relatively rare vascular tumor, which principally occurs in the soft tissue and skin. It most commonly occurs in patients aged 60–79 years and its incidence has increased in recent years. Age at diagnosis, race, and tumor location may affect the overall survival outcomes.
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Shenoy A, Parikh ND. CAQ Corner: Liver transplantation for rare hepatobiliary malignancies. Liver Transpl 2022; 29:644-652. [PMID: 35726389 DOI: 10.1002/lt.26533] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 05/12/2022] [Accepted: 05/26/2022] [Indexed: 01/12/2023]
Affiliation(s)
- Abhishek Shenoy
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA
| | - Neehar D Parikh
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA
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12
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Liu X, Yu H, Zhang Z, Si S, Huang J, Tan H, Teng F, Yang Z. MRI appearances of hepatic epithelioid hemangioendothelioma: a retrospective study of 57 patients. Insights Imaging 2022; 13:65. [PMID: 35380293 PMCID: PMC8982790 DOI: 10.1186/s13244-022-01213-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2021] [Accepted: 03/21/2022] [Indexed: 11/17/2022] Open
Abstract
Background Hepatic epithelioid hemangioendothelioma (HEH) is extremely rare and the MRI features have never been investigated in a large group of patients. Methods A retrospective study was designed to review the MRI images of HEH patients. Two radiologists separately evaluated signal intensity (SI) on unenhanced imaging, morphological features, contrast-enhancement pattern at dynamic study. The MRI features were compared between patients with HEH and hepatic metastatic tumor (HMT). Results Fifty-seven HEH patients were included in this study and a total of 412 lesions were evaluated. On per-lesion analysis, the rate of coalescent lesion and subcapsular lesion were 18.2% and 39.8%, respectively. Capsular retraction and lollipop sign were observed in 47 lesions (11.4%) and 60 lesions (14.6%), respectively. Large lesions (> 5 cm) had the highest rate of coalescent lesion, subcapsular lesion, capsular retraction and lollipop sign. Target sign appeared in 196 lesions (47.6%) on T2 weighted (T2W) and 146 lesions (35.4%) on portal phase. Medium lesions (2–5 cm) had the highest rate of target sign on both T2W (72.9%) and portal phase (55.2%). On per-patient analysis, compare with HEH patients, HMT patients seldom had the appearance of lollipop sign (66.7% versus 6.4%, p < 0.01), capsular retraction (59.6% versus 3.2%, p < 0.01) and target appearance on both T2Wand portal phase (64.9% versus 12.7%, p < 0.01). Conclusion MRI features of HEH correlated with the lesion size. Capsular retraction, lollipop sign and coexistence of target sign on both T2W and portal phase were relatively specific MRI features of HEH, which could be helpful in suggesting the diagnosis.
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Affiliation(s)
- Xiaolei Liu
- Department of Hepatobiliary Surgery, China-Japan Friendship Hospital, 2 Yinghua Dongjie, Hepingli, Beijing, 100029, China
| | - Hongwei Yu
- Department of Radiology, China-Japan Friendship Hospital, Beijing, China
| | - Zihuan Zhang
- Department of Hepatobiliary Surgery, China-Japan Friendship Hospital, 2 Yinghua Dongjie, Hepingli, Beijing, 100029, China
| | - Shuang Si
- Department of Hepatobiliary Surgery, China-Japan Friendship Hospital, 2 Yinghua Dongjie, Hepingli, Beijing, 100029, China
| | - Jia Huang
- Department of Hepatobiliary Surgery, China-Japan Friendship Hospital, 2 Yinghua Dongjie, Hepingli, Beijing, 100029, China
| | - Haidong Tan
- Department of Hepatobiliary Surgery, China-Japan Friendship Hospital, 2 Yinghua Dongjie, Hepingli, Beijing, 100029, China
| | - Feng Teng
- Department of Radiation Oncology, China-Japan Friendship Hospital, 2 Yinghua Dongjie, Hepingli, Beijing, 100029, China.
| | - Zhiying Yang
- Department of Hepatobiliary Surgery, China-Japan Friendship Hospital, 2 Yinghua Dongjie, Hepingli, Beijing, 100029, China.
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Somers N, Creytens D, Van Belle S, Sys G, Lapeire L. Diagnosis of epithelioid hemangioendothelioma eight days postpartum: Is there a link with pregnancy? A case report and review of the literature. Acta Clin Belg 2022; 77:157-162. [PMID: 32741263 DOI: 10.1080/17843286.2020.1802146] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
Epithelioid hemangioendothelioma (EHE) is a rare and heterogeneous malignant vascular tumor. Decision making on a treatment strategy is difficult and a standard of care does not exist. EHE shows a wide age distribution but is rare in children. It can appear anywhere in the body, although lung and liver involvement are most common. There is a female predominance for visceral lesions and several case reports in which EHE developed during or after pregnancy are described in literature, hinting towards a putative role of sex hormones in the course of the disease. We present a case of a 32-year-old woman diagnosed with symptomatic pulmonary metastatic hepatic EHE (HEHE) 8 days postpartum, while the patient was completely asymptomatic before. A wait and see policy was chosen and the patient became asymptomatic in the months following the diagnosis. Although no expression of estrogen and progesterone receptors was found in the diagnostic liver biopsy specimen, we presume that the increased level of sex hormones during pregnancy may have triggered disease progression. The clinical behaviour of the disease in this case report reinforces the suspicion of female hormonal involvement in this type of malignancy and hints toward the potential role of other pregnancy-related factors, e.g. placental growth factor (PlGF), in the development of the disease.
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Affiliation(s)
- Nicky Somers
- Medical School, Ghent University, Ghent, Belgium
| | - David Creytens
- Department of Pathology, Ghent University Hospital, Ghent, Belgium
- Cancer Research Institute Ghent (CRIG), Ghent University Hospital, Ghent, Belgium
| | - Simon Van Belle
- Department of Medical Oncology, Ghent University Hospital, Ghent, Belgium
| | - Gwen Sys
- Cancer Research Institute Ghent (CRIG), Ghent University Hospital, Ghent, Belgium
- Department of Orthopedics and Traumatology, Ghent University Hospital, Ghent, Belgium
| | - Lore Lapeire
- Cancer Research Institute Ghent (CRIG), Ghent University Hospital, Ghent, Belgium
- Department of Medical Oncology, Ghent University Hospital, Ghent, Belgium
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Liu X, Zhang Z, Huang J, Tan H, Yang Z. Efficacy and Safety of Interferon-Alpha 2b for Patients with Hepatic Epithelioid Hemangioendothelioma: Outcomes of a Case-Series Analysis. Cancer Manag Res 2021; 13:8273-8279. [PMID: 34764690 PMCID: PMC8572744 DOI: 10.2147/cmar.s334171] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2021] [Accepted: 10/29/2021] [Indexed: 12/15/2022] Open
Abstract
Background Hepatic epithelioid hemangioendothelioma (HEH) is a rare tumor type. No effective medicine or standard treatment for HEH has been established. Patients and Methods From March 2014 to April 2021, 62 patients with pathologically diagnosed HEH were observed regularly, and interferon-alpha 2b (IFN-a 2b) was administered to patients with progressive disease or reoccurrence. Adverse events (AEs) were assessed and recorded, and a tumor assessment scan was performed every 3 months. Results A total of 42 patients with HEH received IFN-a 2b treatment in this study. No severe (grade ≥3) AEs were reported in the group overall. The most common treatment-related AEs in patients receiving IFN-a 2b were fever (50.0%) and fatigue (21.4%). Partial response and complete response were achieved in 20 patients (47.6%) and 2 patients (4.8%), respectively, and the objective response rate was 52.4%. Stable disease was observed in 12 patients (28.6%), and the disease control rate was 81.0%. Progressive disease was observed in 8 patients (19.0%). The 1-, 3-, and 5-year progression-free survival rates were 81.0%, 69.2%, and 62.3%, respectively. Only 1 patient died as a result of disease progression during the study. The 1-, 3-, and 5-year overall survival rates were 100%, 97.2%, and 97.2%, respectively. Conclusion IFN-a 2b is a safe and effective treatment for patients with HEH. The encouraging results with IFN-a 2b use make it a promising option for patients who have other types of epithelioid hemangioendothelioma; additional clinical trials are needed.
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Affiliation(s)
- Xiaolei Liu
- Department of Hepatobiliary Surgery, China-Japan Friendship Hospital, Beijing, People's Republic of China
| | - Zihuan Zhang
- Department of Hepatobiliary Surgery, China-Japan Friendship Hospital, Beijing, People's Republic of China
| | - Jia Huang
- Department of Hepatobiliary Surgery, China-Japan Friendship Hospital, Beijing, People's Republic of China
| | - Haidong Tan
- Department of Hepatobiliary Surgery, China-Japan Friendship Hospital, Beijing, People's Republic of China
| | - Zhiying Yang
- Department of Hepatobiliary Surgery, China-Japan Friendship Hospital, Beijing, People's Republic of China
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15
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Serji B, Ramdani A, Mirali H, Bouhout T, Bennani A, El Harroudi T. Hepatic epithelioid hemangioendothelioma simulating liver metastasis: A case report. Ann Med Surg (Lond) 2021; 70:102885. [PMID: 34691426 PMCID: PMC8519773 DOI: 10.1016/j.amsu.2021.102885] [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: 08/26/2021] [Revised: 09/20/2021] [Accepted: 09/21/2021] [Indexed: 12/02/2022] Open
Abstract
Introduction Hepatic epithelioid hemangioendothelioma (HEHE) is a rare tumor of vascular origin. Liver involvement is often multinodular simulating metastases. Herein, we report a rare case of HEHE mimicking liver metastases in a female patient. Case presentation A 43-years-old female patient, presented with complaints of pain in the right upper quadrant. Laboratory tests were all within the normal range. Abdominal ultrasound revealed multiple heterogeneous hypoechoic liver lesions. A thoracic and abdominopelvic computed tomography showed bilateral pulmonary micronodules with multiple hypodense hepatic nodules involving both lobes. Percutaneous ultrasound-guided biopsy with pathological study and immunohistochemistry staining revealed the diagnosis of hepatic epithelioid hemangioendothelioma. Discussion HEHE usually involves both liver lobes with three radiological presentations: single nodular, multiple nodular, or diffuse types, the diffuse type reflects an advanced stage. 3/4 of the cases are initially misdiagnosed as liver metastases or primary liver tumors. The pathological study with the immunochemistry stainings confirms the diagnosis. There is no standard treatment for HEHE due to its rarity and lack of prospective randomized studies. Conclusion HEHE is a rare tumor of vascular origin of unknown etiology with malignant potential and unpredictable course. The therapeutic management of this rare condition is not codified and is discussed on a case-by-case basis. Surgical treatment remains the best option with an excellent outcome.
Hepatic epithelioid hemangioendothelioma is a rare tumor of vascular origin. The Clinical presentation and the radiological findings are not specific. Final Diagnosis is made upon pathological study and immunohistochemistry staining. Surgical treatment remain the treatment of choice.
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Affiliation(s)
- Badr Serji
- Surgical Oncology Department, Mohammed VI University Hospital, Regional Oncology Center, Oujda, Morocco.,Mohammed First University Oujda, Faculty of Medicine and Pharmacy Oujda, Oujda, Morocco
| | - Abdelbassir Ramdani
- Surgical Oncology Department, Mohammed VI University Hospital, Regional Oncology Center, Oujda, Morocco.,Mohammed First University Oujda, Faculty of Medicine and Pharmacy Oujda, Oujda, Morocco
| | - Houda Mirali
- Mohammed First University Oujda, Faculty of Medicine and Pharmacy Oujda, Oujda, Morocco.,Radiology Department, Mohammed VI University Hospital, Oujda, Morocco
| | - Tariq Bouhout
- Surgical Oncology Department, Mohammed VI University Hospital, Regional Oncology Center, Oujda, Morocco.,Mohammed First University Oujda, Faculty of Medicine and Pharmacy Oujda, Oujda, Morocco
| | - Amal Bennani
- Mohammed First University Oujda, Faculty of Medicine and Pharmacy Oujda, Oujda, Morocco.,Pathology Department, Mohammed VI University Hospital, Oujda, Morocco
| | - Tijani El Harroudi
- Surgical Oncology Department, Mohammed VI University Hospital, Regional Oncology Center, Oujda, Morocco.,Mohammed First University Oujda, Faculty of Medicine and Pharmacy Oujda, Oujda, Morocco
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Ostojic A, Mrzljak A, Mikulic D. Liver transplantation for benign liver tumors. World J Hepatol 2021; 13:1098-1106. [PMID: 34630877 PMCID: PMC8473500 DOI: 10.4254/wjh.v13.i9.1098] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 05/12/2021] [Accepted: 07/21/2021] [Indexed: 02/06/2023] Open
Abstract
Benign liver tumors are common lesions that are usually asymptomatic and are often found incidentally due to recent advances in imaging techniques and their widespread use. Although most of these tumors can be managed conservatively or treated by surgical resection, liver transplantation (LT) is the only treatment option in selected patients. LT is usually indicated in patients that present with life-threatening complications, when the lesions are diffuse in the hepatic parenchyma or when malignant transformation cannot be ruled out. However, due to the significant postoperative morbidity of the procedure, scarcity of available donor liver grafts, and the benign course of the disease, the indications for LT are still not standardized. Hepatic adenoma and adenomatosis, hepatic hemangioma, and hepatic epithelioid hemangioendothelioma are among the most common benign liver tumors treated by LT. This article reviews the role of LT in patients with benign liver tumors. The indications for LT and long-term outcomes of LT are presented.
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Affiliation(s)
- Ana Ostojic
- Department of Gastroenterology and Hepatology, University Hospital Center Zagreb, Zagreb 10000, Croatia
| | - Anna Mrzljak
- Department of Gastroenterology and Hepatology, University Hospital Center Zagreb, Zagreb 10000, Croatia
| | - Danko Mikulic
- Department of Surgery, University Hospital Merkur, Zagreb 10000, Croatia.
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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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18
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Talakić E, Janek E, Mikalauskas S, Schemmer P. Liver Transplantation in Malignancies: A Comprehensive and Systematic Review on Oncological Outcome. Visc Med 2021; 37:302-314. [PMID: 34540947 PMCID: PMC8406343 DOI: 10.1159/000517328] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Accepted: 05/20/2021] [Indexed: 12/13/2022] Open
Abstract
INTRODUCTION Liver transplantation (LT) is today's standard treatment for both end-stage liver disease and tumors; however, suitable grafts for LT are a scarce resource and outcome after LT is highly dependent on its underlying indication. Thus, patients must be carefully selected to optimize the number of life years gained per graft. This comprehensive and systematic review critically reflects the most recently published oncological outcome data after LT in malignancies based on the preoperative radiological findings. METHODS A systematic literature search was conducted to detect preferentially most recent high-volume series or large database analysis on oncological outcomes after LT for both primary liver cancer and liver metastases between January 1, 2019, and November 14, 2020. A comprehensive review on the radiological assessment of the reviewed liver malignancies is included and its preoperative value for an outcome-driven indication reflected. RESULTS Twenty most recent high-volume or relevant studies including a total number of 2,521 patients were identified including 4, 4, 4, 4, 3, and 1 publications on oncological outcome after LT for hepatocellular carcinoma, cholangiocellular carcinoma, hepatic epitheloid hemangioendothelioma, hepatoblastoma, and both metastatic neuroendocrine tumors and colorectal cancer, respectively. The overall survival is comparable to patients without tumors if patients with malignancies are well selected for LT; however, this is highly dependent on tumor entity, tumor stage, and both neoadjuvant and concomitant treatment. DISCUSSION/CONCLUSION LT is a promising option for better survival in patients with malignant liver tumors in selected patients; however, the indication must be critically discussed prior to LT in every single case in the context of organ shortage.
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Affiliation(s)
- Emina Talakić
- Division of General Radiology, Department of Radiology, Medical University Graz (MUG), Graz, Austria
- Transplant Center Graz, Medical University Graz (MUG), Graz, Austria
| | - Elmar Janek
- Division of General Radiology, Department of Radiology, Medical University Graz (MUG), Graz, Austria
- Transplant Center Graz, Medical University Graz (MUG), Graz, Austria
| | - Saulius Mikalauskas
- Transplant Center Graz, Medical University Graz (MUG), Graz, Austria
- General, Visceral and Transplant Surgery, Department of Surgery, Medical University Graz (MUG), Graz, Austria
| | - Peter Schemmer
- Transplant Center Graz, Medical University Graz (MUG), Graz, Austria
- General, Visceral and Transplant Surgery, Department of Surgery, Medical University Graz (MUG), Graz, Austria
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Merriam P, Nathenson MJ. Liver transplantation for hepatic epithelioid hemangioendothelioma. Cancer 2021; 127:3714-3716. [PMID: 34256414 DOI: 10.1002/cncr.33751] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Revised: 05/03/2021] [Accepted: 05/06/2021] [Indexed: 12/31/2022]
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Stacchiotti S, Miah AB, Frezza AM, Messiou C, Morosi C, Caraceni A, Antonescu CR, Bajpai J, Baldini E, Bauer S, Biagini R, Bielack S, Blay JY, Bonvalot S, Boukovinas I, Bovee JVMG, Boye K, Brodowicz T, Callegaro D, De Alava E, Deoras-Sutliff M, Dufresne A, Eriksson M, Errani C, Fedenko A, Ferraresi V, Ferrari A, Fletcher CDM, Garcia Del Muro X, Gelderblom H, Gladdy RA, Gouin F, Grignani G, Gutkovich J, Haas R, Hindi N, Hohenberger P, Huang P, Joensuu H, Jones RL, Jungels C, Kasper B, Kawai A, Le Cesne A, Le Grange F, Leithner A, Leonard H, Lopez Pousa A, Martin Broto J, Merimsky O, Merriam P, Miceli R, Mir O, Molinari M, Montemurro M, Oldani G, Palmerini E, Pantaleo MA, Patel S, Piperno-Neumann S, Raut CP, Ravi V, Razak ARA, Reichardt P, Rubin BP, Rutkowski P, Safwat AA, Sangalli C, Sapisochin G, Sbaraglia M, Scheipl S, Schöffski P, Strauss D, Strauss SJ, Sundby Hall K, Tap WD, Trama A, Tweddle A, van der Graaf WTA, Van De Sande MAJ, Van Houdt W, van Oortmerssen G, Wagner AJ, Wartenberg M, Wood J, Zaffaroni N, Zimmermann C, Casali PG, Dei Tos AP, Gronchi A. Epithelioid hemangioendothelioma, an ultra-rare cancer: a consensus paper from the community of experts. ESMO Open 2021; 6:100170. [PMID: 34090171 PMCID: PMC8182432 DOI: 10.1016/j.esmoop.2021.100170] [Citation(s) in RCA: 106] [Impact Index Per Article: 26.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Revised: 05/07/2021] [Accepted: 05/11/2021] [Indexed: 12/22/2022] Open
Abstract
Epithelioid hemangioendothelioma (EHE) is an ultra-rare, translocated, vascular sarcoma. EHE clinical behavior is variable, ranging from that of a low-grade malignancy to that of a high-grade sarcoma and it is marked by a high propensity for systemic involvement. No active systemic agents are currently approved specifically for EHE, which is typically refractory to the antitumor drugs used in sarcomas. The degree of uncertainty in selecting the most appropriate therapy for EHE patients and the lack of guidelines on the clinical management of the disease make the adoption of new treatments inconsistent across the world, resulting in suboptimal outcomes for many EHE patients. To address the shortcoming, a global consensus meeting was organized in December 2020 under the umbrella of the European Society for Medical Oncology (ESMO) involving >80 experts from several disciplines from Europe, North America and Asia, together with a patient representative from the EHE Group, a global, disease-specific patient advocacy group, and Sarcoma Patient EuroNet (SPAEN). The meeting was aimed at defining, by consensus, evidence-based best practices for the optimal approach to primary and metastatic EHE. The consensus achieved during that meeting is the subject of the present publication.
This consensus paper provides key recommendations on the management of epithelioid hemangioendothelioma (EHE). Recommendations followed a consensus meeting between experts and a representative of the EHE advocacy group and SPAEN. Authorship includes a multidisciplinary group of experts from different institutions from Europe, North America and Asia.
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Affiliation(s)
- S Stacchiotti
- Adult Mesenchymal Tumor and Rare Cancer Unit, Cancer Medicine Department, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
| | - A B Miah
- The Royal Marsden Hospital and The Institute of Cancer Research, London, UK
| | - A M Frezza
- Adult Mesenchymal Tumor and Rare Cancer Unit, Cancer Medicine Department, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - C Messiou
- Department of Radiology, The Royal Marsden Hospital and The Institute of Cancer Research, London, UK
| | - C Morosi
- Radiology Department, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - A Caraceni
- Palliative Care Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - C R Antonescu
- Department of Pathology, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, USA
| | - J Bajpai
- Medical Oncology Department, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India
| | - E Baldini
- Department of Radiation Oncology, Dana-Farber Cancer Center/Brigham and Women's Hospital, Boston, USA
| | - S Bauer
- Department of Medical Oncology, West German Cancer Center, Sarcoma Center, University of Duisburg-Essen, University Hospital, Essen, Germany
| | - R Biagini
- Orthopaedic Department, Regina Elena National Cancer Institute, Rome, Italy
| | - S Bielack
- Klinikum Stuttgart - Olgahospital, Zentrum für Kinder-, Jugend- und Frauenmedizin, Stuttgart Cancer Center, Pädiatrische Onkologie, Hämatologie, Immunologie, Stuttgart, Germany
| | - J Y Blay
- Department of Medical Oncology, Centre Leon Berard, Université Claude Bernard Lyon, Unicancer, Lyon, France
| | - S Bonvalot
- Department of Surgical Oncology, Institut Curie, Université Paris Sciences et Lettres, Paris, France
| | | | - J V M G Bovee
- Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands
| | - K Boye
- Department of Oncology, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway
| | - T Brodowicz
- Medical University Vienna & General Hospital Department of Internal Medicine 1/Oncology, Vienna, Austria
| | - D Callegaro
- Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - E De Alava
- Institute of Biomedicine of Sevilla (IBiS), Virgen del Rocio University Hospital/CSIC/University of Sevilla/CIBERONC, Seville, Spain; Department of Normal and Pathological Cytology and Histology, School of Medicine, University of Seville, Seville, Spain
| | | | - A Dufresne
- Department of Medical Oncology, Centre Leon Berard, Université Claude Bernard Lyon, Unicancer, Lyon, France
| | - M Eriksson
- Department of Oncology, Skane University Hospital and Lund University, Lund, Sweden
| | - C Errani
- Orthopaedic Service, Musculoskeletal Oncology Department, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
| | - A Fedenko
- Medical Oncology Division, P.A. Herzen Cancer Research Institute, Moscow, Russian Federation
| | - V Ferraresi
- Sarcomas and Rare Tumors Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy
| | - A Ferrari
- Paediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - C D M Fletcher
- Department of Pathology Brigham & Women's Hospital, Boston, USA
| | - X Garcia Del Muro
- University of Barcelona and Genitourinary Cancer and Sarcoma Unit Institut Català d'Oncologia, Hospitalet, Barcelona, Spain
| | - H Gelderblom
- Department of Medical Oncology, Leiden University Medical Center, Leiden, The Netherlands
| | - R A Gladdy
- University of Toronto and Lunenfeld-Tanenbaum Research Institute, Toronto, Canada
| | - F Gouin
- Department of Surgery, Centre Leon Berard, Lyon, France
| | - G Grignani
- Division of Medical Oncology, Candiolo Cancer Institute, FPO - IRCCS, Candiolo, Italy
| | - J Gutkovich
- The EHE Foundation, Wisconsin, USA; NUY Langone Medical Center, New York, USA
| | - R Haas
- Department of Radiotherapy, the Netherlands Cancer Institute, Amsterdam, the Netherlands; Department of Radiotherapy, the Leiden University Medical Center, Leiden, the Netherlands
| | - N Hindi
- Group of Advanced Therapies and Biomarkers in Sarcoma, Institute of Biomedicine of Seville (IBIS, HUVR, CSIC, Universidad de Sevilla), Seville, Spain
| | - P Hohenberger
- Division of Surgical Oncology & Thoracic Surgery, Mannheim University Medical Center, University of Heidelberg, Heidelberg, Germany
| | - P Huang
- Division of Molecular Pathology, The Institute of Cancer Research, London, UK
| | - H Joensuu
- Department of Oncology, Helsinki University Hospital & Helsinki University, Helsinki, Finland
| | - R L Jones
- Department of Cancer, The Royal Marsden Hospital and The Institute of Cancer Research, London, UK
| | - C Jungels
- Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium
| | - B Kasper
- University of Heidelberg, Mannheim University Medical Center, Sarcoma Unit, Mannheim, Germany
| | - A Kawai
- Musculoskeletal Oncology and Rehabilitation Medicine, Rare Cancer Center National Cancer Center Hospital, Tokyo, Japan
| | - A Le Cesne
- International Department, Gustave Roussy, Villejuif, France
| | - F Le Grange
- UCLH - University College London Hospitals NHS Foundation Trust, London, UK
| | - A Leithner
- Department of Orthopaedics and Trauma Medical University Graz, Graz, Austria
| | - H Leonard
- Chair of Trustees of the EHE Rare Cancer Charity (UK), Charity number 1162472
| | - A Lopez Pousa
- Medical Oncology Department, Hospital Universitario Santa Creu i Sant Pau, Barcelona, Spain
| | - J Martin Broto
- Hospital Universitario Fundación Jimenez Diaz, Madrid, Spain
| | - O Merimsky
- Unit of Soft Tissue and Bone Oncology, Division of Oncology, Tel-Aviv Medical Center affiliated with Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - P Merriam
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, USA
| | - R Miceli
- Department of Clinical Epidemiology and Trial Organisation, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - O Mir
- Sarcoma Group, Gustave Roussy, Villejuif, France
| | - M Molinari
- University of Pittsburgh Medical Center, Thomas Starzl Transplant Institute, Pittsburgh, USA
| | | | - G Oldani
- Division of Abdominal Surgery, University Hospitals of Geneva, Geneva, Switzerland
| | - E Palmerini
- Chemotherapy Unit, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
| | - M A Pantaleo
- Division of Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - S Patel
- Sarcoma Center, The University of Texas M.D. Anderson Cancer Center, Houston, USA
| | | | - C P Raut
- Department of Surgery, Brigham and Women's Hospital, Boston, USA; Center for Sarcoma and Bone Oncology, Harvard Medical School, Boston, USA; Dana Farber Cancer Center, Harvard Medical School, Boston, USA
| | - V Ravi
- Sarcoma Center, The University of Texas M.D. Anderson Cancer Center, Houston, USA
| | - A R A Razak
- Princess Margaret Cancer Centre and Sinai Healthcare System & Faculty of Medicine, University of Toronto, Toronto, Canada
| | - P Reichardt
- Helios Klinikum Berlin-Buch, Department of Oncology and Palliative Care, Berlin, Germany
| | - B P Rubin
- Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, USA
| | - P Rutkowski
- Maria Sklodowska-Curie National Research Institute of Oncology, Department of Soft Tissue/Bone Sarcoma and Melanoma, Warsaw, Poland
| | - A A Safwat
- Aarhus University Hospital, Aarhus, Denmark
| | - C Sangalli
- Department of Radiation Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - G Sapisochin
- Multi-Organ Transplant and HPB Surgical Oncology, Division of General Surgery, Department of Surgery, University of Toronto, Toronto, Canada
| | - M Sbaraglia
- Department of Pathology, Azienda Ospedaliera Università Padova, Padua, Italy
| | - S Scheipl
- Department of Orthopaedics and Trauma, Medical University of Graz, Graz, Austria
| | | | - D Strauss
- Department of Surgery, The Royal Marsden Hospital and The Institute of Cancer Research, London, UK
| | - S J Strauss
- University College London Hospital, London, UK
| | - K Sundby Hall
- Department of Oncology, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway
| | - W D Tap
- Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, USA
| | - A Trama
- Department of Research, Evaluative Epidemiology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - A Tweddle
- Palliative Care, The Royal Marsden Hospital and The Institute of Cancer Research London
| | - W T A van der Graaf
- Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - M A J Van De Sande
- Department of Orthopedic Surgery Bone and Soft Tissue Tumor Unit, Leiden University Medical Center, Leiden, The Netherlands
| | - W Van Houdt
- Sarcoma and Melanoma Unit, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - G van Oortmerssen
- Co-Chair of Sarcoma Patients EuroNet (SPAEN), Woelfersheim, Germany & Chairman of the Dutch organisation for sarcoma patients (Patiëntenplatform Sarcomen), Guest researcher at Leiden University (Leiden Institute for Advanced Computer Science), Leiden University, Leiden, The Netherlands
| | - A J Wagner
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, USA
| | - M Wartenberg
- Chair of the Board of Directors of Sarcoma Patients EuroNet (SPAEN), Sarcoma Patients EuroNet (SPAEN), Woelfersheim, Germany
| | - J Wood
- The Royal Marsden NHS Foundation Trust, London, UK
| | - N Zaffaroni
- Molecular Pharmacology Unit, Department of Applied Research and Technological Development, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - C Zimmermann
- Department of Supportive Care, Princess Margaret Cancer Centre and Division of Palliative Medicine, Department of Medicine, University of Toronto, Toronto, Canada
| | - P G Casali
- Adult Mesenchymal Tumor and Rare Cancer Unit, Cancer Medicine Department, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - A P Dei Tos
- Department of Pathology, Azienda Ospedaliera Università Padova, Padua, Italy
| | - A Gronchi
- Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
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21
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Witte S, Weidema M, Kaal S, Versleijen-Jonkers Y, Flucke U, van der Graaf W, Desar I. The heterogeneity of Epithelioid Hemangioendothelioma (EHE): A case series and review of the literature with emphasis on treatment options. Semin Oncol 2021; 48:111-118. [PMID: 34176654 DOI: 10.1053/j.seminoncol.2021.04.002] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2019] [Revised: 04/07/2021] [Accepted: 04/14/2021] [Indexed: 12/28/2022]
Abstract
Epithelioid hemangioendothelioma (EHE) is an extremely rare vascular sarcoma with a very heterogeneous presentation and prognosis. We here present five cases of EHE emphasizing diversity in presentation, treatment, and prognosis. Furthermore, we present a review of the literature on EHE treatment options.
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Affiliation(s)
- Stijn Witte
- Department of Medical Oncology, Radboud University Medical Centre, Nijmegen, The Netherlands
| | - Marije Weidema
- Department of Medical Oncology, Radboud University Medical Centre, Nijmegen, The Netherlands
| | - Suzanne Kaal
- Department of Medical Oncology, Radboud University Medical Centre, Nijmegen, The Netherlands
| | | | - Uta Flucke
- Department of Medical Oncology, Radboud University Medical Centre, Nijmegen, The Netherlands
| | - Winette van der Graaf
- Department of Medical Oncology, Radboud University Medical Centre, Nijmegen, The Netherlands
| | - Ingrid Desar
- Department of Medical Oncology, Radboud University Medical Centre, Nijmegen, The Netherlands.
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22
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Chahrour MA, Khachfe HH, Habib JR, El-Asmar R, Saifi O, Jamali FR. Treatment and Prognosis of Hepatic Epithelioid Hemangioendothelioma: A SEER Database Analysis. World J Surg 2021; 45:2886-2894. [PMID: 33999226 DOI: 10.1007/s00268-021-06165-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/24/2021] [Indexed: 12/20/2022]
Abstract
BACKGROUND Hepatic epithelioid hemangioendothelioma (HEH) is a rare tumor that can affect multiple organs. Little is known about the pathophysiology, clinical course and management of this disease. The aim of this study is to determine survival rates and elucidate the role of various prognostic factors and therapeutic modalities as compared to surgery on patients with HEH. METHODS A retrospective analysis on patients diagnosed with HEH between 2004 and 2016 was performed utilizing the SEER database. Kaplan-Meier curves were constructed to determine overall and cancer-specific survival, and the log-rank test was used to compare between groups. To explore prognostic factors and treatment outcomes, univariable and multivariable Cox proportional hazard models were developed. RESULTS A total of 353 patients with HEH (median age: 50.4 years) were identified. The most common surgery performed was liver resection (90.8%). One-year OS in the surgical group and non-surgical group was 86.6% and 61.0%, respectively, while 5-year OS was 75.2% and 37.4%, respectively. On multivariable analysis, surgery emerged as a favorable prognostic factor [HR (95%CI): 0.404 (0.215-0.758) p value = 0.005]. Age > 65 years [HR (95%CI): 2.548 (1.442-4.506) p value = 0.001] and tumor size > 10 cm [HR (95%CI): 2.401 (1.319-4.37) p value = 0.004] were shown to be poor survival prognostic factors. CONCLUSION HEH is a rare disease that is poorly understood. Surgical intervention is associated with improved survival rates. Multicenter prospective collaborations are needed to improve our limited knowledge about this neoplasm and determine the optimal treatment strategy.
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Affiliation(s)
- Mohamad A Chahrour
- Department of Surgery, American University of Beirut Medical Center, Beirut, Lebanon
| | - Hussein H Khachfe
- Department of Surgery, American University of Beirut Medical Center, Beirut, Lebanon
| | - Joseph R Habib
- Department of Surgery, Johns Hopkins University, Baltimore, MD, USA
| | - Rudy El-Asmar
- Department of Surgery, American University of Beirut Medical Center, Beirut, Lebanon
| | - Omran Saifi
- Department of Radiation Oncology, Mayo Clinic, Jacksonville, FL, USA
| | - Faek R Jamali
- Division of General Surgery, Sheikh Shakhbout Medical City, Abu Dhabi, United Arab Emirates.
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23
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Finotti M, Auricchio P, Vitale A, Gringeri E, Cillo U. Liver transplantation for rare liver diseases and rare indications for liver transplant. Transl Gastroenterol Hepatol 2021; 6:27. [PMID: 33824931 DOI: 10.21037/tgh-19-282] [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: 10/14/2019] [Accepted: 06/12/2020] [Indexed: 12/13/2022] Open
Abstract
Liver transplantation (LT) is currently considered the gold standard treatment for end-stage liver failure. Compared to the first decades of its use, LT is associated with lower comorbidity and mortality, with a 5-year survival over 70%. Worldwide, liver cirrhosis and hepatocellular carcinoma represent the major indications to LT. However, almost 1% of LT is performed for rare diseases or rare indications, which include non-hepatocellular malignancy, vascular disorders, metabolic and congenital liver disorders. These diseases can lead to hepatocellular necrosis, biliary tree abnormality and/or hepatomegaly. Most of these diseases are not associated with liver failure but in highly selected patients, LT represent an effective therapy improving the overall survival and quality of life. Rare indications for LT often overlap with rare diseases. However, rare LT indications for non-rare diseases are rising in the last decades, especially for benign primary liver tumor, colon rectal liver metastasis, neuroendocrine liver metastasis, and cholangiocarcinoma (CCA). Non-rare diseases with rare indication for LT and rare adult disease with an indication for LT are categorized and discussed in detail, focusing on some disorders for which the literature provides a more definitive evidence base. Early referral to a transplant center is encouraged to provide an effective therapeutic option in these non-standard indications for LT.
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Affiliation(s)
- Michele Finotti
- Department of Surgery, Oncology and Gastroenterology, Hepatobiliary Surgery and Liver Transplantation Unit, Padova University Hospital, Padova, Italy
| | - Pasquale Auricchio
- Department of Surgery, Oncology and Gastroenterology, Hepatobiliary Surgery and Liver Transplantation Unit, Padova University Hospital, Padova, Italy
| | - Alessandro Vitale
- Department of Surgery, Oncology and Gastroenterology, Hepatobiliary Surgery and Liver Transplantation Unit, Padova University Hospital, Padova, Italy
| | - Enrico Gringeri
- Department of Surgery, Oncology and Gastroenterology, Hepatobiliary Surgery and Liver Transplantation Unit, Padova University Hospital, Padova, Italy
| | - Umberto Cillo
- Department of Surgery, Oncology and Gastroenterology, Hepatobiliary Surgery and Liver Transplantation Unit, Padova University Hospital, Padova, Italy
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24
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Na BG, Hwang S, Ahn CS, Kim KH, Moon DB, Ha TY, Song GW, Jung DH, Park GC, Yoon YI, Kang WH, Cho HD, Kim SH, Hong SM, Lee SG. Prognosis of hepatic epithelioid hemangioendothelioma after living donor liver transplantation. KOREAN JOURNAL OF TRANSPLANTATION 2021; 35:15-23. [PMID: 35769618 PMCID: PMC9235330 DOI: 10.4285/kjt.20.0049] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Revised: 11/05/2020] [Accepted: 11/06/2020] [Indexed: 12/24/2022] Open
Abstract
Background Epithelioid hemangioendothelioma (EHE) is a rare borderline vascular tumor. Due to its rarity and protean behavior, the optimal treatment of hepatic EHE has not yet been standardized. This single-center study describes outcomes in patients with hepatic EHE who underwent living donor liver transplantation (LDLT). Methods The medical records of patients who underwent LDLT for hepatic EHE from 2007 to 2016 were reviewed. Results During 10-year period, four patients, one man and three women, of mean age 41.3±11.1 years, underwent LDLT for hepatic EHE. Based on imaging modalities, these patients were preoperatively diagnosed with EHE or hepatocellular carcinoma, with percutaneous liver biopsy confirming that all four had hepatic EHE. The tumors were multiple and scattered over entire liver, precluding liver resection. Blood tumor markers were not elevated, except that CA19-9 and des-γ-carboxy prothrombin was slightly elevated in one patient. Mean model for end-stage liver disease score was 10.8±5.7. All patients underwent LDLT using modified right liver grafts, with graft-recipient weight ratio of 1.11±0.19, and all recovered uneventfully after LDLT. One patient died due to tumor recurrence at 9 months, whereas the other three have done well without tumor recurrence, resulting in 5-year disease-free and overall patient survival rates of 75% each. The patient with tumor recurrence was classified as a high-risk patient based on the original and modified hepatic EHE-LT scoring systems. Conclusions LDLT can be an effective treatment for patients with unresectable hepatic EHEs that are confined within the liver and absence of macrovascular invasion and lymph node metastasis.
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Affiliation(s)
- Byeong-Gon Na
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Shin Hwang
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Chul-Soo Ahn
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Ki-Hun Kim
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Deok-Bog Moon
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Tae-Yong Ha
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Gi-Won Song
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Dong-Hwan Jung
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Gil-Chun Park
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Young-In Yoon
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Woo-Hyoung Kang
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hwui-Dong Cho
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sang Hoon Kim
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Seung-Mo Hong
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sung-Gyu Lee
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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25
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Chu KKW, Wong KHC, Chok KSH. Expanding Indications for Liver Transplant: Tumor and Patient Factors. Gut Liver 2021; 15:19-30. [PMID: 32102130 PMCID: PMC7817931 DOI: 10.5009/gnl19265] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2019] [Revised: 11/29/2019] [Accepted: 11/29/2019] [Indexed: 12/16/2022] Open
Abstract
During the past few decades, liver transplant has developed from a high-mortality procedure to an almost routine procedure with good survival outcomes. The development of living donor liver transplant has increased the availability of liver grafts, and the scope of indications for liver transplant has been expanding ever since. The aim of this review is to provide an overview of such an expansion of scope. Various criteria have been proposed to expand the eligibility of patients with hepatocellular carcinoma exceeding the Milan criteria for liver transplant. Furthermore, liver transplant is increasingly performed as a treatment modality for cholangiocarcinoma, neuroendocrine liver metastasis and colorectal liver metastasis. The number of elderly patients receiving liver transplant is on the rise. Combined organ transplantation has also been adopted to treat patients with multiple organ failure. Going forward, further development of preoperative noninvasive predictors in tumor, patient and even donor factors is needed to identify patients at risk of poor outcomes and hence optimize patient management.
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Affiliation(s)
- Kevin Ka-Wan Chu
- Department of Surgery, The University of Hong Kong, Hong Kong, China
| | | | - Kenneth Siu-Ho Chok
- Department of Surgery and State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China
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26
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Chen LJ, Han YD, Zhang M. Diagnosis value preoperative localization of insulinoma by diffusion-weighted imaging: A pilot study. Medicine (Baltimore) 2020; 99:e23048. [PMID: 33285682 PMCID: PMC7717785 DOI: 10.1097/md.0000000000023048] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Insulinoma is the most common functional neuroendocrine tumor that originates from the islet of beta cells. Insulinoma is usually an isolated benign tumor and small in size (<2 cm). Due to the small size of the lesion, it often leads to difficulty in clinical preoperative localization diagnosis. However, we have unexpectedly discovered that the diffusion-weighted-imaging (DWI) adds great value in the preoperative localization diagnosis of insulinoma in non-invasive examination technique.We verified using operative pathology data and retrospectively analyzed the clinical and imageology findings of 5 cases who reported to have an insulinoma. All the 5 cases underwent DWI examination, among non-contrast enhanced magnetic resonance imaging (MRI) in 1 case, contrast-enhanced MRI in 4 cases.Five cases of DWI showed a nodular high signal <1.3 cm with pancreatic tail in 3 cases, pancreatic neck, and pancreatic head in 1 case each, respectively. Non-contrast enhanced MRI showed suspicious abnormal signals in the tail of the pancreas were detected in 1 case. MRI enhanced scans presented 2 cases with abnormal enhancement in the arterial phase and 2 cases without abnormal enhancement in arterial phase. Also, 3 cases showed mild persistence enhanced in the portal venous phase and delayed phase. However, 1 case remained normal in the portal venous phase and the delay period.DWI examination has high clinical value in the localization diagnosis of insulinoma and thus it can be used as a routine examination for preoperative localization diagnosis.
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Affiliation(s)
- Li-Jun Chen
- The Department for Radiology, Gao Xin Hospital Xi’an
| | - Yue-Dong Han
- The Department for Radiology, Gao Xin Hospital Xi’an
| | - Ming Zhang
- The First Affiliated Hospital of Xi’an Jiao Tong University, Xi’an, ShannXi, China
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27
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Brahmbhatt M, Prenner S, Bittermann T. Liver Transplantation for Hepatic Epithelioid Hemangioendothelioma Is Facilitated by Exception Points With Acceptable Long-term Outcomes. Transplantation 2020; 104:1187-1192. [PMID: 31577674 DOI: 10.1097/tp.0000000000002982] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Hepatic epithelioid hemangioendothelioma (HEHE) is a rare vascular tumor with a high mortality rate. HEHE is now a formally recognized indication for exception point priority in the United States under the new National Liver Review Board. The role of liver transplantation (LT) and exception point waitlist priority in the United States for patients with HEHE remains understudied. METHODS This was a retrospective cohort study using the United Network for Organ Sharing transplant database. From February 27, 2002 to January 31, 2018, 131 adults waitlisted for LT with HEHE were identified by free-text entry. RESULTS Exception point applications were submitted for 91.6% (120/131) of patients. All patients with fully reviewed applications received exception points at least once during waitlisting, and 85% (103/120) upon first submission. Among the 88 patients transplanted, median model for end-stage liver disease score at LT was 7 ((interquartile range [IQR]: 6-11) and waiting time 78.5 days (IQR: 29.5-237.5). Unadjusted post-LT survival of HEHE recipients at 1-, 3-, and 5-years from LT was 88.6%, 78.9%, and 77.2%. Unadjusted post-LT patient and graft survival of HEHE patients was not different from patients with hepatocellular carcinoma within Milan receiving exception point priority (P = 0.08). An increased rate of graft failure due to hepatic artery thrombosis ≤14 days from initial LT was observed in HEHE versus non-HEHE patients (4.6% versus 0.5%). CONCLUSIONS The majority of HEHE recipients receive exception points at a universal approval rate allowing prompt access to deceased donor LT.
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Affiliation(s)
- Mihir Brahmbhatt
- Division of General Internal Medicine, University of Pennsylvania, Philadelphia, PA
| | - Stacey Prenner
- Division of Gastroenterology & Hepatology, University of Pennsylvania, Philadelphia, PA
| | - Therese Bittermann
- Division of Gastroenterology & Hepatology, University of Pennsylvania, Philadelphia, PA.,Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA
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28
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Krasnodębski M, Grąt M, Morawski M, Wierzchowski M, Jastrzębski M, Remiszewski P, Zając K, Patkowski W, Zieniewicz K. Hepatic Epithelioid Hemangioendothelioma: A Rare Disease With Favorable Outcomes After Liver Transplantation. Transplant Proc 2020; 52:2447-2449. [PMID: 32217012 DOI: 10.1016/j.transproceed.2020.02.101] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Accepted: 02/05/2020] [Indexed: 11/28/2022]
Abstract
BACKGROUND Hepatic epithelioid hemangioendothelioma (HEHE) is a rare vascular tumor with indolent behavior in terms of malignancy. The treatment of choice is either resection in the case of resectable lesions or liver transplantation (LT) for the disseminated intrahepatic form. The aim of this study was to investigate the outcomes of patients with HEHE treated by LT. MATERIAL AND METHODS There were 18 patients with HEHE who underwent LT between 2002 and 2018 included in this retrospective study. The study group was comprised of young recipients (median age of 39 years) and mainly women (15 of 18; 83.3%). Two recipients had concomitant tumors of epithelioid hemangioendothelioma in the liver and lungs prior to LT. The survival probability was calculated using the Kaplan-Meier estimator. RESULTS According to histopathological data, none of the patients had a macrovascular invasion. In 4 patients (22.2%), the disease had spread to the hilar lymph nodes. The maximum diameter of the tumor in the studied group was 18 cm. The survival probability after 1, 5, and 15 years was 94.0%, 82.6%, and 41.3%, respectively. No disease recurrence was observed during a median follow-up of 65.9 months. CONCLUSION Liver transplantation provides favorable outcomes for selected patients with a hepatic form of epithelioid hemangioendothelioma.
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Affiliation(s)
- Maciej Krasnodębski
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Warsaw, Poland.
| | - Michał Grąt
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
| | - Marcin Morawski
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
| | - Michał Wierzchowski
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
| | - Maciej Jastrzębski
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
| | - Piotr Remiszewski
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
| | - Krzysztof Zając
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
| | - Waldemar Patkowski
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
| | - Krzysztof Zieniewicz
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
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Kou K, Chen YG, Zhou JP, Sun XD, Sun DW, Li SX, Lv GY. Hepatic epithelioid hemangioendothelioma: Update on diagnosis and therapy. World J Clin Cases 2020; 8:3978-3987. [PMID: 33024754 PMCID: PMC7520791 DOI: 10.12998/wjcc.v8.i18.3978] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2020] [Revised: 08/12/2020] [Accepted: 08/21/2020] [Indexed: 02/05/2023] Open
Abstract
With an estimated incidence of only 1-2 cases in every 1 million people, hepatic epithelioid hemangioendothelioma (HEHE) is a rare vascular endothelial cell tumor occurring in the liver and consisting of epithelioid and histiocyte-like vascular endothelial cells in mucus or a fibrotic matrix. HEHE is characterized as a low-to-moderate grade malignant tumor and is classified into three types: solitary, multiple, and diffuse. Both the etiology and characteristic clinical manifestations of HEHE are unclear. However, HEHE has a characteristic appearance on imaging including ultrasound, magnetic resonance imaging, and positron emission tomography/computerized tomography. Still, its diagnosis depends mainly on pathological findings, with immunohistochemical detection of endothelial markers cluster of differentiation 31 (CD31), CD34, CD10, vimentin, and factor VIII antigen as the basis of diagnosis. Hepatectomy and/or liver transplantation are the first choice for treatment, but various chemotherapeutic drugs are reportedly effective, providing a promising treatment option. In this review, we summarize the literature related to the diagnosis and treatment of HEHE, which provides future perspectives for the clinical management of HEHE.
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Affiliation(s)
- Kai Kou
- Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun 130021, Jilin Province, China
| | - Yu-Guo Chen
- Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun 130021, Jilin Province, China
| | - Jian-Peng Zhou
- Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun 130021, Jilin Province, China
| | - Xiao-Dong Sun
- Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun 130021, Jilin Province, China
| | - Da-Wei Sun
- Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun 130021, Jilin Province, China
| | - Shu-Xuan Li
- Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun 130021, Jilin Province, China
| | - Guo-Yue Lv
- Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun 130021, Jilin Province, China
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Fan YH, Tang HN, Zhou JP, Fang Q, Li SX, Kou K, Lv GY. Fast-growing epithelioid hemangioendothelioma of the liver: A case report. Medicine (Baltimore) 2020; 99:e22077. [PMID: 32899078 PMCID: PMC7478780 DOI: 10.1097/md.0000000000022077] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023] Open
Abstract
RATIONALE Hepatic epithelioid hemangioendothelioma (HEH) is a rare vascular tumor of the liver with malignant potential. It can be of solitary type, multifocal type, or diffuse type. Although there are some characteristic features on radiologic imaging, the definitive diagnosis of HEH is based on histopathology. The surgical treatment of HEH includes liver resection and transplant. PATIENT CONCERNS A middle-aged woman presented with easy fatiguability and anorexia for 1 month was found to have multifocal lesions on radiological imaging. DIAGNOSIS HEH was diagnosed by needle biopsy. It can be seen from imaging that this case is a multifocal form. The largest lesion increased from 3 to 3.3 cm within 2 months, with an increase of 9.45%; no other relevant literatures have been reported. INTERVENTIONS The possibility of liver transplantation was suggested to the patient. However, the patient refused transplantation and was successfully treated by radical right hepatectomy and resection of the left lobe lesion. OUTCOMES She remained disease-free throughout a year follow-up period. CONCLUSION HEH is a rare disease with characteristic radiological and pathological features. Although liver transplantation is the preferred treatment for multifocal HEH, surgical excision represents one alternative when the lesions can be guaranteed to be completely excised.
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Sanduzzi-Zamparelli M, Rimola J, Montironi C, Nunes V, Alves VAF, Sapena V, da Fonseca LG, Forner A, Carrilho FJ, Díaz A, Fuster C, Ferrer J, Fuster J, Ayuso C, Solé M, Bruix J, Reig M. Hepatic epithelioid hemangioendothelioma: An international multicenter study. Dig Liver Dis 2020; 52:1041-1046. [PMID: 32535084 DOI: 10.1016/j.dld.2020.05.003] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2020] [Revised: 05/02/2020] [Accepted: 05/04/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Hepatic epithelioid hemangioendothelioma is an ultra-rare hepatic vascular tumor, diagnosed more frequently in females. The knowledge about this tumor derives mainly from small case series with sub-optimal treatment outcomes. The aim of this study is to identify the clinical and radiological issues helpful to develop an international prospective registry. METHODS We conducted an international multicentric and retrospective study of patients with hepatic hemangioendothelioma. The clinical, pathological and radiological images collected during follow-up were reviewed. Central radiological revision was performed and 3 patterns of contrast were defined. RESULTS Between 1994 and 2016, 27 patients with hepatic hemangioendothelioma were identified in three institutions but the final diagnosis was hepatic angiosarcoma in one. The majority were females, median age was 38.7-years and 17 patients were asymptomatic at diagnosis. No patient had Two out of ten (20%) patients had surgical specimens with positive macro-vascular invasion and 50% had extrahepatic disease, and the most frequent pattern was the progressive-central-contrast-uptake. After a median follow-up of 6.7-years, the 5- and 10-year survival rates are 91.5% and 51.9%, respectively. CONCLUSIONS This multicentric study shows the heterogeneous profile of patients with hepatic hemangioendothelioma, reflecting the need to establish a reference network in order to better characterize these patients and ultimately develop a personalized treatment strategy.
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Affiliation(s)
- Marco Sanduzzi-Zamparelli
- BCLC group. Liver Unit. Hospital Clinic de Barcelona. IDIBAPS. CIBERehd. University of Barcelona, Barcelona, Spain
| | - Jordi Rimola
- BCLC group. Radiology Department, Hospital Clínic de Barcelona. CIBERehd. University of Barcelona, Barcelona, Catalonia-Spain
| | | | - Vinicius Nunes
- Universidade Federal da Bahia, Salvador da Bahía, Brazil
| | - Venancio Avancini Ferreira Alves
- Department of Pathology, University of São Paulo School of Medicine CICAP Hospital Alemão Oswaldo Cruz, São Paulo, São Paulo, Brazil
| | - Víctor Sapena
- BCLC group. Liver Unit. Hospital Clinic de Barcelona. IDIBAPS. CIBERehd. University of Barcelona, Barcelona, Spain
| | - Leonardo Gomes da Fonseca
- Clinical Oncology Instituto do Cancer de São Paulo Hospital das Clinicas, University of São Paulo School of Medicine, São Paulo, Brazil
| | - Alejandro Forner
- BCLC group. Liver Unit. Hospital Clinic de Barcelona. IDIBAPS. CIBERehd. University of Barcelona, Barcelona, Spain
| | - Flair José Carrilho
- Division of Clinical Gastroenterology and Hepatology Hospital das Clinicas, University of São Paulo School of Medicine, São Paulo, Brazil
| | - Alba Díaz
- BCLC group. Department of Pathology. Hospital Clinic de Barcelona. IDIBAPS. University of Barcelona, Barcelona, Spain
| | - Carla Fuster
- BCLC group. Department of Pathology. Hospital Clinic de Barcelona. IDIBAPS. University of Barcelona, Barcelona, Spain
| | - Joana Ferrer
- BCLC group. Liver Surgery and Transplant Unit Digestive and Metabolic DIseases Institute. Hospital Clinic de Barcelona. University of Barcelona, Barcelona, Spain
| | - Josep Fuster
- BCLC group. Liver Surgery and Transplant Unit Digestive and Metabolic DIseases Institute. Hospital Clinic de Barcelona. University of Barcelona, Barcelona, Spain
| | - Carmen Ayuso
- BCLC group. Radiology Department, Hospital Clínic de Barcelona. CIBERehd. University of Barcelona, Barcelona, Catalonia-Spain
| | - Manel Solé
- BCLC group. Department of Pathology. Hospital Clinic de Barcelona. IDIBAPS. University of Barcelona, Barcelona, Spain
| | - Jordi Bruix
- BCLC group. Liver Unit. Hospital Clinic de Barcelona. IDIBAPS. CIBERehd. University of Barcelona, Barcelona, Spain
| | - Maria Reig
- BCLC group. Liver Unit. Hospital Clinic de Barcelona. IDIBAPS. CIBERehd. University of Barcelona, Barcelona, Spain.
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Hepatic Epithelioid Hemangioendothelioma as a Rare Indication for Liver Transplantation. Transplant Proc 2020; 52:1453-1454. [PMID: 32241636 DOI: 10.1016/j.transproceed.2020.01.090] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2019] [Accepted: 01/10/2020] [Indexed: 12/23/2022]
Abstract
BACKGROUND Hepatic epithelioid hemangioendothelioma (HEHE) is a rare neoplasm of vascular origin, with nonspecific presentation and unpredictable clinical course. Several therapeutic options are available according to the literature, including chemotherapy and radiotherapy, liver resection (LR), and liver transplantation (LT). METHODS We present 2 cases of patients with HEHE treated with liver transplantation in our center, a 30-year-old man and a 42-year-old woman, diagnosed with several lesions involving both liver lobes. RESULTS Levels of tumor markers (carcinoembryonic antigen [CEA], cancer antigen 19.9 [Ca19.9], and alpha-fetoprotein [AFP]) were negative. Percutaneous biopsy revealed HEHE in both cases. Due to the bilobar location, liver transplantation was performed. Postoperative course was unremarkable, and no significant complications developed. At this time, 10 and 5 years' follow-up has concluded, respectively. Both patients remain alive, asymptomatic, with normal liver function and no sign of recurrence. CONCLUSIONS HEHE is an uncommon malignant hepatic disease. Most cases present with bilobar involvement, and LT is probably the most useful treatment with favorable outcomes according to the literature and our experience. Further studies are needed to establish the optimal management of this rare entity.
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Virarkar M, Saleh M, Diab R, Taggart M, Bhargava P, Bhosale P. Hepatic Hemangioendothelioma: An update. World J Gastrointest Oncol 2020; 12:248-266. [PMID: 32206176 PMCID: PMC7081107 DOI: 10.4251/wjgo.v12.i3.248] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Revised: 02/21/2020] [Accepted: 02/23/2020] [Indexed: 02/05/2023] Open
Abstract
Primary epithelioid hemangioendotheliomas of the liver (EHL) are rare tumors with a low incidence. The molecular background of EHL is still under investigation, with WWTR1-CAMPTA1 mutation may function as a tumor marker. Commonly, this tumor is misdiagnosed with angiosarcoma, cholangiocarcinomas, metastatic carcinoma, and hepatocellular carcinoma (sclerosing variant). Characteristic features on imaging modalities such as ultrasound, computed tomography, magnetic resonance imaging and positron emission tomography/computed tomography guide in diagnosis and staging. The "halo sign" and the "lollipop sign" on computed tomography and magnetic resonance imaging are described in the literature. Currently, there are no standardized guidelines for treating EHL with treatment options are broad including: chemotherapy, ablation, surgery and liver transplantation with inconsistent results.
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Affiliation(s)
- Mayur Virarkar
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
| | - Mohammed Saleh
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
| | - Radwan Diab
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
| | - Melissa Taggart
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
| | - Peeyush Bhargava
- Department of Radiology, The University of Medical Branch, Galveston, TX 77555, United States
| | - Priya Bhosale
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
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Telli TA, Okten IN, Tuylu TB, Demircan NC, Arikan R, Alan O, Ercelep O, Ones T, Yildirim AT, Dane F, Yumuk PF. VEGF-VEGFR pathway seems to be the best target in hepatic epithelioid hemangioendothelioma: A case series with review of the literature. Curr Probl Cancer 2020; 44:100568. [PMID: 32201052 DOI: 10.1016/j.currproblcancer.2020.100568] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2020] [Accepted: 03/02/2020] [Indexed: 12/15/2022]
Abstract
Epithelioid hemangioendothelioma (EHE) is a rare vascular tumor originating from endothelial cells. Clinical aspect of the disease covers a wide spectrum from a low-grade tumor to a fatal cancer. Most common sites of EHE are reported as lung, liver and bone. Hepatic EHE (HEHE) is a clinical form with an incidence of less than 1 person in a million. Due to rarity of the disease, there is no standard therapy established. Surgery and liver transplantation still seem to be the best approach if possible. However, most of the patients present with unresectable or metastatic disease. Many conventional chemotherapeutic agents and antiangiogenic drugs have been reported previously in the literature with inconsistent outcomes. Here we report 4 cases of HEHE, who benefit distinctly from anti-VEGF treatments in different settings. While combination of paclitaxel and bevacizumab resulted in partial response in 3 patients, one of them also achieved long-term disease stabilization with bevacizumab maintenance with no adverse event. Two of the patients had clear benefit from pazopanib during the course of disease. One patient was treated with thalidomide for 18 months with stable disease, and is still being followed without any treatment. Although targeting VEGF-VEGFR pathway seems to be the best approach in HEHE, randomized studies are urgently needed to support these findings.
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Affiliation(s)
- Tugba Akin Telli
- Division of Medical Oncology, Department of Internal Medicine, Marmara University School of Medicine, Istanbul, Turkey
| | - Ilker Nihat Okten
- Division of Medical Oncology, Department of Internal Medicine, Medeniyet University School of Medicine, Istanbul, Turkey
| | - Tuğba Basoglu Tuylu
- Division of Medical Oncology, Department of Internal Medicine, Marmara University School of Medicine, Istanbul, Turkey
| | - Nazim Can Demircan
- Division of Medical Oncology, Department of Internal Medicine, Marmara University School of Medicine, Istanbul, Turkey
| | - Rukiye Arikan
- Division of Medical Oncology, Department of Internal Medicine, Marmara University School of Medicine, Istanbul, Turkey
| | - Ozkan Alan
- Division of Medical Oncology, Department of Internal Medicine, Marmara University School of Medicine, Istanbul, Turkey
| | - Ozlem Ercelep
- Division of Medical Oncology, Department of Internal Medicine, Marmara University School of Medicine, Istanbul, Turkey
| | - Tunc Ones
- Department of Nucleer Medicine, Marmara University School of Medicine, Istanbul, Turkey
| | | | - Faysal Dane
- Division of Medical Oncology, Department of Internal Medicine, Marmara University School of Medicine, Istanbul, Turkey
| | - Perran Fulden Yumuk
- Division of Medical Oncology, Department of Internal Medicine, Marmara University School of Medicine, Istanbul, Turkey
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Noh OK, Kim SS, Yang MJ, Lim SG, Hwang JC, Cho HJ, Cheong JY, Cho SW. Treatment and prognosis of hepatic epithelioid hemangioendothelioma based on SEER data analysis from 1973 to 2014. Hepatobiliary Pancreat Dis Int 2020; 19:29-35. [PMID: 31822393 DOI: 10.1016/j.hbpd.2019.11.006] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2019] [Accepted: 11/25/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND Hepatic epithelioid hemangioendothelioma (HEH) is a rare tumor of vascular origin with an unknown etiology, a low incidence, and a variable natural course. We evaluated the management and prognosis of HEH from the Surveillance, Epidemiology and End Results (SEER) program and changes in treatment modalities of HEH over 30 years. METHODS From 1973 to 2014 in the SEER database, we selected patients diagnosed with HEH. We analyzed the clinical characteristics, patterns of management, and clinical outcomes of patients with HEH. RESULTS We identified 79 patients with HEH (median age: 54.0 years; male to female ratio: 1:2.6). The initial extent of disease was local in 22 (27.8%) patients, regional metastasis in 22 (27.8%), distant metastasis in 31 (39.2%) and unknown in 4 (5.1%). The median size of primary tumor was 3.85 cm (interquartile range, 2.50-7.93 cm). Among 74 patients with available management data, the most common management was no treatment (29/74, 39.2%), followed by chemotherapy only (22/74, 29.7%), liver resection-based (13/74, 17.6%), and transplantation-based therapy (6/74, 8.1%). The 5-year cancer-specific survival rate was 57.8%. Patients who underwent surgical treatment had significantly higher survival than those who underwent non-surgical treatment (5-year survival; 88% vs. 49%, P = 0.019). Multivariate analysis revealed that surgical therapy was the only independent prognostic factor for survival (hazard ratio: 0.20, P = 0.040). CONCLUSIONS Resection or liver transplantation is worth considering for treatment of patients with HEH.
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Affiliation(s)
- O Kyu Noh
- Department of Radiation Oncology, Ajou University School of Medicine, Suwon, Korea; Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, Korea; Office of Biostatistics, Ajou Research Institute for Innovative Medicine, Ajou University Medical Center, Suwon, Korea
| | - Soon Sun Kim
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea.
| | - Min Jae Yang
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea
| | - Sun Gyo Lim
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea
| | - Jae Chul Hwang
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea
| | - Hyo Jung Cho
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea
| | - Jae Youn Cheong
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea
| | - Sung Won Cho
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea
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Kim KS, Kim JM, Lee JS, Choi GS, Cho JW, Lee SK. Stent insertion and balloon angioplasty for portal vein stenosis after liver transplantation: long-term follow-up results. ACTA ACUST UNITED AC 2020; 25:231-237. [PMID: 31063137 DOI: 10.5152/dir.2019.18155] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
PURPOSE It is not easy to determine whether balloon angioplasty or stenting should be performed in patients with portal vein stenosis after liver transplantation. We aimed to propose appropriate indication by evaluating long-term outcomes of balloon angioplasty and stent insertion in adult liver transplant patients. METHODS We retrospectively reviewed 31 patients with portal vein stenosis among 1369 patients who underwent adult liver transplantation from January 2001 to December 2015. When stenosis was confirmed by venography, angioplasty was performed first. When there was no flow improvement or pressure gradient was not decreased after angioplasty, stent insertion was performed. We also performed primary stent insertion without angioplasty for diffuse stenosis, kinking, external compression, and near occlusion of portal vein in venography. We assessed patency in patients who underwent percutaneous transluminal angioplasty and stent insertion through regular outpatient follow-up and evaluated technical and clinical success and long-term results. RESULTS Technical success was 85% and 100% in balloon angioplasty and stent insertion, respectively. Clinical success was achieved in 78% of balloon angioplasties and in 100% of stent insertions. At 1, 5, and 10 years after balloon angioplasty, patency rates were 87%, 82%, and 68% respectively, and the rates of stent patency were all 100%. Portal vein size measured during the operation of patients with and without recurrence were 19±4.2 mm and 19±3.0 mm (P = 0.956), respectively. The balloon size of patients with and without recurrence were 11±1.95 mm and 14±1.66 mm, respectively (P = 0.013), when balloon angioplasty was performed after stenosis diagnosis. CONCLUSION Stent insertion can be considered when fibrotic changes are expected due to repeated inflammation and when the balloon size to be used is small. Balloon angioplasty seems less risky for anastomotic ruptures in portal vein stenosis in the early post liver transplantation period.
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Affiliation(s)
- Kyeong Sik Kim
- Department of Surgery-Transplantation, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jong Man Kim
- Department of Surgery-Transplantation, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Ji Soo Lee
- Department of Surgery-Transplantation, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Gyu Sung Choi
- Department of Surgery-Transplantation, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jae-Won Cho
- Department of Surgery-Transplantation, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Suk-Koo Lee
- Department of Surgery-Transplantation, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
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Cao L, Hong J, Zhou L, Ye Y, Liu Y, Yu J, Zheng S. Selection of treatment for hepatic epithelioid hemangioendothelioma: a single-center experience. World J Surg Oncol 2019; 17:183. [PMID: 31699108 PMCID: PMC6839190 DOI: 10.1186/s12957-019-1729-y] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2019] [Accepted: 10/15/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hepatic epithelioid hemangioendothelioma (HEHE) is a rare angiogenic tumor with no recognized effective treatment. Treatment options used worldwide include liver transplantation (LT), liver resection (LR), radiofrequency ablation (RFA), chemotherapy, and observation. The aim of this study was to describe the efficacy of different treatment options used for HEHE at our center. METHODS The medical charts of 12 patients with HEHE (9 women and 3 men) who were diagnosed and treated at the First Affiliated Hospital of Zhejiang University, China, between January 2011 and December 2017 were retrospectively reviewed. RESULTS The patients were diagnosed by postoperative histopathology or fine needle aspiration biopsy. Two patients with diffuse lesions received LT and were alive without recurrence at the last follow-up. Three patients received LR as the initial treatment, and all of them developed recurrence during the follow-up period. One patient received RFA and remained free of disease, while the remaining six patients opted for simple observation rather than treatment. One of the patients who received LR passed away because of tumor recurrence within 32 months after surgery; the other patients showed no significant disease activity after treatments for their recurrent lesions. As of April 2018, the mean follow-up duration was 39.6 ± 20.1 months (15-82 months). CONCLUSIONS There are multiple strategies for HEHE. Considering its indolent course, initial observation for assessment of the lesion behavior may aid in the selection of appropriate treatment. Surgery or LT is suitable for patients with disease progression during the observation period. However, our sample size was small, and further studies are required to gather more information that can aid in optimal treatment selection.
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Affiliation(s)
- Linping Cao
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China
| | - Jiawei Hong
- Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China
| | - Lingfeng Zhou
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China
| | - Yufu Ye
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China
| | - Yuanxing Liu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China
| | - Jun Yu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China
| | - Shusen Zheng
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China. .,Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China.
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Liver transplantation for unresectable malignancies: Beyond hepatocellular carcinoma. Eur J Surg Oncol 2019; 45:2268-2278. [PMID: 31387755 DOI: 10.1016/j.ejso.2019.07.024] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2019] [Revised: 07/02/2019] [Accepted: 07/18/2019] [Indexed: 12/12/2022] Open
Abstract
Indications for liver transplantation have expanded over the past few decades owing to improved outcomes and better understanding of underlying pathologies. In particular, there has been a growing interest in the field of transplant oncology in recent years that has led to considerable developments which have pushed the boundaries of malignant indications for liver transplantation beyond hepatocellular carcinoma (HCC). In this article, we review and summarise the published evidence for liver transplantation in non-HCC primary and metastatic liver malignancies and highlight ongoing clinical trials that address unresolved questions therein. We also examine the current technical, immunological and oncological challenges that face liver transplantation in this growing field and explore potential approaches to overcome these barriers.
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39
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Recent advances in liver transplantation for cancer: The future of transplant oncology. JHEP Rep 2019; 1:377-391. [PMID: 32039389 PMCID: PMC7005652 DOI: 10.1016/j.jhepr.2019.07.004] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2019] [Revised: 07/15/2019] [Accepted: 07/16/2019] [Indexed: 02/06/2023] Open
Abstract
Liver transplantation is widely indicated as a curative treatment for selected patients with hepatocellular carcinoma. However, with recent therapeutic advances, as well as efforts to increase the donor pool, liver transplantation has been carefully expanded to patients with other primary or secondary malignancies in the liver. Cholangiocarcinoma, colorectal and neuroendocrine liver metastases, and hepatic epithelioid haemangioendothelioma are amongst the most relevant new indications. In this review we discuss the fundamental concepts of this ambitious undertaking, as well as the newest indications for liver transplantation, with a special focus on future perspectives within the recently established concept of transplant oncology.
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40
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Lazăr DC, Avram MF, Romoșan I, Văcariu V, Goldiș A, Cornianu M. Malignant hepatic vascular tumors in adults: Characteristics, diagnostic difficulties and current management. World J Clin Oncol 2019; 10:110-135. [PMID: 30949442 PMCID: PMC6441663 DOI: 10.5306/wjco.v10.i3.110] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2019] [Revised: 02/23/2019] [Accepted: 03/12/2019] [Indexed: 02/06/2023] Open
Abstract
Malignant vascular tumors of the liver include rare primary hepatic mesenchymal tumors developed in the background of a normal liver parenchyma. Most of them are detected incidentally by the increased use of performing imaging techniques. Their diagnosis is challenging, involving clinical and imaging criteria, with final confirmation by histology and immunohistochemistry. Surgery represents the mainstay of treatment. Liver transplantation (LT) has improved substantially the prognosis of hepatic epithelioid hemangioendothelioma (HEHE), with 5-year patient survival rates of up to 81%, based on the European Liver Intestine Transplantation Association-European Liver Transplant Registry study. Unfortunately, the results of surgery and LT are dismal in cases of hepatic angiosarcoma (HAS). Due to the disappointing results of very short survival periods of approximately 6-7 mo after LT, because of tumor recurrence and rapid progression of the disease, HAS is considered an absolute contraindication to LT. Recurrences after surgical resection are high in cases of HEHE and invariably present in cases of HAS. The discovery of reliable prognostic markers and the elaboration of prognostic scores following LT are needed to provide the best therapeutic choice for each patient. Studies on a few patients have demonstrated the stabilization of the disease in a proportion of patients with hepatic vascular tumors using novel targeted antiangiogenic agents, cytokines or immunotherapy. These new approaches, alone or in combination with other therapeutic modalities, such as surgery and classical chemotherapy, need further investigation to assess their role in prolonging patient survival. Personalized therapeutic algorithms according to the histopathological features, behavior, molecular biology and genetics of the tumors should be elaborated in the near future for the management of patients diagnosed with primary malignant vascular tumors of the liver.
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Affiliation(s)
- Daniela Cornelia Lazăr
- Department of Internal Medicine I, University Medical Clinic, University of Medicine and Pharmacy “Victor Babeş”, Timişoara 300041, Romania
| | - Mihaela Flavia Avram
- Department of Surgery X, 1st Surgery Clinic, University of Medicine and Pharmacy “Victor Babeş”, Timişoara 300041, Romania
| | - Ioan Romoșan
- Department of Internal Medicine I, University Medical Clinic, University of Medicine and Pharmacy “Victor Babeş”, Timişoara 300041, Romania
| | - Violetta Văcariu
- Department of Internal Medicine I, University Medical Clinic, University of Medicine and Pharmacy “Victor Babeş”, Timişoara 300041, Romania
| | - Adrian Goldiș
- Department of Gastroenterology and Hepatology, University of Medicine and Pharmacy “Victor Babeş”, Timişoara 300041, Romania
| | - Mărioara Cornianu
- Department of Pathology, University of Medicine and Pharmacy “Victor Babeş”, Timişoara 300041, Romania
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López-Gutiérrez JC. Clinical and economic impact of surgery for treating infantile hemangiomas in the era of propranolol: overview of single-center experience from La Paz Hospital, Madrid. Eur J Pediatr 2019; 178:1-6. [PMID: 30421264 DOI: 10.1007/s00431-018-3290-z] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2018] [Revised: 06/09/2018] [Accepted: 11/05/2018] [Indexed: 11/25/2022]
Abstract
Propranolol has changed the management of infantile hemangiomas (IHs). We summarize the evolution of surgical treatment for IH at La Paz Children's Hospital (Madrid) in the era of propranolol, with a focus on hepatic IHs.Retrospectively, we compared surgical treatment of IHs in children referred during the periods 2004-2009 and 2009-2014. Hepatic IH mortality rates before and after the introduction of propranolol therapy were evaluated specifically.The majority of hemangiomas needing surgical excision were located on the head/face/scalp of female patients. Since the introduction of propranolol therapy, surgery for IH has decreased from about 60 to 6 procedures/year at our institution and no transplants for hepatic IH have been registered.Conclusions: Surgical procedures for IH have decreased by about 90% at our institution since the introduction of propranolol treatment and hepatic IH have not needed liver transplantation. Referrals for surgery for IH are generally the consequence of absent or delayed propranolol treatment. Given the significant reduction in the number of surgical procedures, propranolol can be considered as having a strong economic and social impact. What is Known: • The use of oral propranolol solution is currently considered as the treatment of choice in the management of infantile hemangiomas. • Propranolol treatment achieves better outcomes and less side effects than systemic corticosteroids. What is New: • Social and financial impact of the significant reduction in the number of reconstructive surgical procedures and liver transplants due to the use of propranolol in tertiary health institutions remains to be analyzed.
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Cousin S, Le Loarer F, Crombé A, Karanian M, Minard-Colin V, Penel N. [Epithelioid hemangioendothelioma]. Bull Cancer 2018; 106:73-83. [PMID: 30527817 DOI: 10.1016/j.bulcan.2018.11.004] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2018] [Revised: 10/28/2018] [Accepted: 11/01/2018] [Indexed: 12/14/2022]
Abstract
We describe herein the inaugural manifestations, the radiological and histological diagnosis criteria for and the outcome of epithelioid hemangioendothelioma (EHE). Most of EHE (90%) display a specific reciprocal chromosomic translocation t(1;3)(p36;q23-25), which is associated with the synthesis of fusion protein WWTR1/CAMTA1. EHE are low-grade vascular sarcomas. EHE could be initially localized or multifocal. At localized stage, EHE are best treated with focal treatments. At multifocal stage, the upfront strategy is watchful follow-up. Some multifocal EHE display very indolent course with spontaneous stable disease for years or decades. In case of progressive multifocal EHE, there is no consensual treatment. Diagnostic and clinical management of EHE requires interdisciplinary expertise from labeled centers.
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Affiliation(s)
- Sophie Cousin
- Institut Bergonié, département d'oncologie médicale, 229, cours de l'Argonne, 33000 Bordeaux, France
| | - François Le Loarer
- Institut Bergonié, département d'anatomopathologie, 229, cours de l'Argonne, 33000 Bordeaux, France
| | - Amandine Crombé
- Institut Bergonié, département d'imagerie médicale, 229, cours de l'Argonne, 33000 Bordeaux, France
| | - Marie Karanian
- Centre Léon Bérard, département d'anatomopathologie, 28, Promenade Léa et Napoléon Bullukian, 69008 Lyon, France
| | - Véronique Minard-Colin
- Institut Gustave Roussy, département d'oncologie pédiatrique, 114, rue Edouard-Vaillant, 94800 Villejuif, France
| | - Nicolas Penel
- Centre Oscar Lambret, département d'oncologie médicale, 3, rue Frédéric Combemale, 59000 Lille, France; Hôpital Claude Huriez, service d'oncologie médicale, rue Michel Polonowski, 59000 Lille, France.
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Lerut J, Iesari S. Vascular tumours of the liver: a particular story. Transl Gastroenterol Hepatol 2018; 3:62. [PMID: 30363746 PMCID: PMC6182012 DOI: 10.21037/tgh.2018.09.02] [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: 08/27/2018] [Accepted: 09/03/2018] [Indexed: 12/12/2022] Open
Abstract
Vascular tumours of the liver represent an underrated chapter of medical and surgical hepatology. These tumours cover a wide spectrum ranging from the frequent and most benign hepatic haemangioma (HH), via the rare and intermediately aggressive hepatic epithelioid haemangioendothelioma (HEHE) to the rare and most malignant hepatic haemangiosarcoma (HHS). In contrast to the treatment algorithms for hepatocellular and cholangiocellular cancer, the diagnostic and therapeutic approaches to HEHE and HHS are not well developed. The related uncertainty is explained by their rare occurrence and their protean clinical, morphological (imaging) and histopathological presentation and behaviour. This article gives an update about these particular tumours based on the analysis of the recent literature and of the studies on vascular tumours published by the European Liver Intestine Transplantation Association (ELITA)-European Liver Transplant Registry (ELTR). It focuses also on the place of liver transplantation (LT) in the respective therapeutic algorithms. The differential diagnosis between these vascular and other tumour types may be very difficult. Correct diagnosis is of utmost importance and is based on a high index of clinical suspicion and on the integration of clinical, radiological, histological [including immunohistochemistry (IHC) and molecular biology findings]. Surgery, be it partial or total hepatectomy (LT), should be proposed whenever possible, because it is the therapeutic mainstay. In HEHE, LT provides excellent results, with long-term disease-free survivals (DFS) reaching 75%. Good results can be obtained even in case of (frequent) extrahepatic spread. Based on the extensive ELITA-ELTR study a HEHE-LT prognostic score has been proposed in order to estimate the risk of recurrence after LT. In contrast, results of surgery and LT are extremely poor for HHS, for the almost invariably rapid recurrence (within 6 months) and related death within 2 years. LT remains a contraindication for HHS. Due to the still important recurrence rate after surgical resection (25% in HEHE and almost 100% in HHS), there is an urgent need to develop pharmacological treatments targeting angiogenic and non-VEGF angiogenic pathways. To date, some prospective pilot studies and case reports have shown some short-term stabilisation of the disease in small groups of patients. In order to make progress, combination of surgery, anti-angiogenic and immunotherapy seems worthwhile. To complete the panel of vascular liver tumours, infantile haemangioendothelioma, haemangiopericytoma, nodular regenerative hyperplasia (NRH) and hepatic small vessel neoplasms (HSVN) are also discussed.
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Affiliation(s)
- Jan Lerut
- Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain (UCL), Brussels, Belgium
| | - Samuele Iesari
- Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain (UCL), Brussels, Belgium
- Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, L’Aquila, Italy
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Kamarajah SK, Robinson D, Littler P, White SA. Small, incidental hepatic epithelioid haemangioendothelioma the role of ablative therapy in borderline patients. J Surg Case Rep 2018; 2018:rjy223. [PMID: 30151113 PMCID: PMC6101624 DOI: 10.1093/jscr/rjy223] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2018] [Accepted: 08/02/2018] [Indexed: 02/07/2023] Open
Abstract
Primary hepatic epithelioid hemangioendothelioma (HEHE) is an extremely rare tumor of vascular origin with an incidence of <0.1 per 100 000 population. We describe a 70-year-old man with renal cell carcinoma managed via robotic right partial nephrectomy who was also found to have a solitary 10 mm lesion on a pre-operative staging computer tomography (CT) scan. The patient underwent percutaneous biopsy and local ablation of the lesion consistent with an epithelioid hepatic haemangioendothelioma. Post-procedure CT scan after 1 month showed adequate ablation margins with no new lesions. The role of local ablation for solitary, small HEHE is discussed.
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Affiliation(s)
- Sivesh K Kamarajah
- Department of Hepatopancreatobiliary and Transplantation Surgery, Freeman Hospital, Newcastle upon Tyne, UK
| | - Daniel Robinson
- Department of Hepatopancreatobiliary and Transplantation Surgery, Freeman Hospital, Newcastle upon Tyne, UK
| | - Pete Littler
- Department of Hepatopancreatobiliary and Transplantation Surgery, Freeman Hospital, Newcastle upon Tyne, UK
| | - Steven A White
- Department of Hepatopancreatobiliary and Transplantation Surgery, Freeman Hospital, Newcastle upon Tyne, UK
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Hepatic epithelioid hemangioendothelioma: A misdiagnosed rare liver tumor. Presse Med 2018; 47:182-185. [PMID: 29373279 DOI: 10.1016/j.lpm.2017.10.026] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2017] [Revised: 09/21/2017] [Accepted: 10/25/2017] [Indexed: 02/06/2023] Open
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Haberal Reyhan N. Liver Transplant for Nonhepatocellular Carcinoma Malignancy. EXP CLIN TRANSPLANT 2017; 15:69-73. [PMID: 28302003 DOI: 10.6002/ect.tond16.l18] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
Liver transplant is now an acceptable and effective treatment for specific nonhepatocellular malignancies. Worldwide, hilar cholangiocarcinoma accounts for 3% of all primary gastrointestinal malignancies and for 10% of primary hepatobiliary malignancies. For patients who have early-stage, unresectable cholangiocarcinoma, liver transplant preceded by neoadjuvant radiotherapy can result in tumor-free margins, accomplish a radical resection, and treat the underlying primary sclerosing cholangitis when present. Hepatic epithelioid hemangioendothelioma is a rare tumor of vascular origin with a variable malignant potential. Excellent results have been reported with liver transplant for patients with unresectable hepatic epithelioid hemangioendothelioma, with 1-year and 10-year survival rates of 96% and 72%. Hepatoblastoma is the most common primary hepatic malignancy in children. The long-term survival rate after transplant ranges from 66% to 77% in patients with unresectable tumors and good response to chemotherapy. Metastatic liver disease is not an indication for liver transplant, with the exception of cases in which the primary tumor is a neuroendocrine tumor. Indication for liver transplant for hepatic metastasis from neuroendocrine tumors is mainly for patients with unresectable tumors and for palliation of medically uncontrollable symptoms. Posttransplant survival in those patients with low tumor activity index is excellent, despite recurrence of the tumor. Some recent data on liver transplant for unresectable hepatic metastases from colorectal cancer have reported limited survival benefits compared with previous reports. However, due to the high rate of tumor recurrence in a very short time after liver transplant, especially in the era of organ shortage, this indication has not been favored by the transplant community. The indications for liver transplant for nonhepatocellular carcinoma malignancy and its limitations have evolved dramatically over the past decades and will continue to be redefined through future research and investigations.
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47
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Lai Q, Feys E, Karam V, Adam R, Klempnauer J, Oliverius M, Mazzaferro V, Pascher A, Remiszewski P, Isoniemi H, Pirenne J, Foss A, Ericzon BG, Markovic S, Lerut JP. Hepatic Epithelioid Hemangioendothelioma and Adult Liver Transplantation: Proposal for a Prognostic Score Based on the Analysis of the ELTR-ELITA Registry. Transplantation 2017; 101:555-564. [PMID: 28212256 DOI: 10.1097/tp.0000000000001603] [Citation(s) in RCA: 69] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Hepatic epithelioid hemangioendothelioma (HEHE) is a rare vascular tumor which has an intermediate aggressive behavior. Although the value of liver transplantation (LT) is well established, its place in the management of HEHE is still unclear. The aim of this study is to confirm, based on a very large patient cohort, the value of LT in the management of HEHE and to identify risk factors for post-LT recurrence. METHODS The outcome of 149 transplant recipients with HEHE recorded in the European Liver Transplant Registry during the period November 1984 to May 2014 was analyzed. Median post-LT follow-up was 7.6 years (interquartile range, 2.8-14.4). RESULTS Cox regression analysis showed that macrovascular invasion (hazard ratio [HR], 4.8; P < 0.001), pre-LT waiting time of 120 days or less (HR, 2.6; P = 0.01) and hilar lymph node invasion (HR = 2.2; P = 0.03), but not pre-LT extrahepatic disease, were significant risk factors for recurrence. These findings, which were also confirmed in a propensity score analysis, allowed the development of a HEHE-LT score enabling stratification of patients in relation to their risk of tumor recurrence. Patients with a score of 2 or less had a much better 5-year disease-free survival compared to those having a score of 6 or higher (93.9% vs 38.5%; P < 0.001). CONCLUSIONS The analysis of this (largest in the world) HEHE adult liver recipient cohort clearly confirms the value of LT in the treatment of this rare disorder and also permits identification of patients at risk of posttransplant recurrence. Posttransplant follow-up should take the HEHE-LT score into account. Extrahepatic disease localization is reconfirmed not to be a contraindication for LT.
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Affiliation(s)
- Quirino Lai
- 1 Starzl Abdominal Transplant Unit, University Hospitals St. Luc, Université catholique Louvain, Brussels, Belgium. 2 Centre Hépatobiliaire Paul Brousse, Paris, France. 3 Medizinsche Hochschule Hannover, Hannover, Germany. 4 Transplancenter IKEM, Prague, Czech Republic. 5 Istituto Nazionale Tumori, Milano, Italy. 6 Charité Campus Virchow Klinikum, Berlin, Germany. 7 Department of General Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland. 8 UCJ Helsingfors, Helsinki, Finland. 9 Department Abdominal transplantation Surgery, Universitaire Ziekenhuizen Gasthuisberg KULeuven, Belgium. 10 Rikshospitalet, Oslo Universitetssykehus, Oslo, Norway. 11 Karolinska University Hospital, Huddinge, Stockholm, Sweden. 12 University Medical Centre Ljubljana, Ljubljana, Slovenia
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Giardino A, Miller FH, Kalb B, Ramalho M, Martin DR, Rodacki K, Woosley JT, Semelka RC. Hepatic epithelioid hemangioendothelioma: a report from three university centers. Radiol Bras 2016; 49:288-294. [PMID: 27818541 PMCID: PMC5094816 DOI: 10.1590/0100-3984.2015.0059] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
Objective To determine common imaging findings of hepatic epithelioid
hemangioendothelioma on magnetic resonance images. Materials and Methods A search was made of three institutional databases between January 2000 and
August 2012. Seven patients (mean age, 47 years; range, 21-66 years; 6
women) with pathology-confirmed diagnosis of hepatic epithelioid
hemangioendothelioma who had undergone magnetic resonance imaging were
identified. None of the patients had received any treatment for hepatic
epithelioid hemangioendothelioma at the time of the initial magnetic
resonance imaging examination. Results Hepatic epithelioid hemangioendothelioma tumors appeared as focal masses in
7/7 patients, greater than 5 in number, with a coalescing lesion in 1/5, and
peripheral localization in 6/7. Capsular retraction was present in 4/7, and
was associated with peripherally located lesions. Early ring enhancement was
appreciated in the majority of lesions in 7/7 patients. Centripetal
progressive enhancement was shown in 5/7 patients on venous phase that
exhibited a distinctive thick inner border of low signal on venous phase
images, and a central core of delayed enhancement. Small lesions did not
show this. Conclusion The combination of multifocal round-configuration lesions that are
predominantly peripheral and exhibit early peripheral ring enhancement and
late appearance of an inner thick border of low signal and central core of
high signal may represent an important feature for hepatic epithelioid
hemangioendothelioma.
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Affiliation(s)
- Antonello Giardino
- MD, Department of Radiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Universitá degli Studi di Milano, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy
| | - Frank H Miller
- MD, FACR, Department of Radiology, Northwestern Memorial Hospital, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Bobby Kalb
- MD, Department of Radiology, University of Arizona Medical Center, Tucson, Arizona, USA; Department of Radiology, The Emory Clinic, Wesley Woods Geriatric Hospital, Atlanta, GA, USA
| | - Miguel Ramalho
- Department of Radiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Radiology, Hospital Garcia de Orta, Almada, Portugal
| | - Diego R Martin
- MD, PhD, Department of Radiology, University of Arizona Medical Center, Tucson, Arizona, USA; Department of Radiology, The Emory Clinic, Wesley Woods Geriatric Hospital, Atlanta, GA, USA
| | - Karina Rodacki
- MD, Department of Radiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Ecomax - Centro de Diagnóstico por Imagem, Blumenau, SC, Brazil
| | - John T Woosley
- MD, PhD, Department of Pathology & Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Richard C Semelka
- MD, Department of Radiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
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Liver transplantation for hepatobiliary malignancies: a new era of "Transplant Oncology" has begun. Surg Today 2016; 47:403-415. [PMID: 27130463 DOI: 10.1007/s00595-016-1337-1] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2015] [Accepted: 04/06/2016] [Indexed: 01/10/2023]
Abstract
The indications of liver transplantation for hepatobiliary malignancies have been carefully expanded in a stepwise fashion, despite the fundamental limitations in oncological, immunological, and technical aspects. A new era of "Transplant Oncology," the fusion of transplant surgery and surgical oncology, has begun, and we stand at the dawn of a paradigm shift in multidisciplinary cancer treatment. For hepatocellular carcinoma, new strategies have been undertaken to select recipients based on biological and dynamic markers instead of conventional morphological and static parameters, opening the doors for a more deliberate expansion of the Milan criteria and locoregional therapies before liver transplantation. Neoadjuvant chemoradiation therapy followed by liver transplantation for unresectable perihilar cholangiocarcinoma developed by the Mayo Clinic provided excellent outcomes in a US multicenter study; however, the surgical indications are not necessarily universal and await international validation. Similarly, an aggressive multidisciplinary approach has been applied for other tumors, including intrahepatic cholangiocarcinoma, hepatoblastoma, liver metastases from colorectal and neuroendocrine primary and gastrointestinal stromal tumors as well as rare tumors, such as hepatic undifferentiated embryonal sarcoma and infantile choriocarcinoma. In conclusion, liver transplantation is an important option for hepatobiliary malignancies; however, prospective studies are urgently needed to ensure the appropriate patient selection, organ allocation and living donation policies, and administration of antineoplastic immunosuppression.
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Aggressive Recurrence of Primary Hepatic Epithelioid Haemangioendothelioma after Liver Transplantation. Can J Gastroenterol Hepatol 2016; 2016:6135297. [PMID: 27446853 PMCID: PMC4904699 DOI: 10.1155/2016/6135297] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2015] [Accepted: 09/15/2015] [Indexed: 12/11/2022] Open
Abstract
HEHE is a rare neoplasm of vascular origin that occurs in the liver; UNOS reported a favorable outcome after liver transplantation in 110 patients with 1-year and 5-year survival of 80% and 64%. Case Report. A 40-year-old lady presented with a three-month history of right upper abdominal pain with nausea, vomiting, and significant loss of weight associated with scleral icterus and progressive abdominal distension. Examination revealed jaundice, hepatomegaly, and ascites. Serum bilirubin was 26.5 mg/dL and ALP was 552 CT. Abdomen and pelvis showed diffuse infiltrative neoplastic process of the liver with a mass effect and stretching of the hepatic and portal veins, in addition to bile duct dilatation. Viral hepatitis markers were negative and serum alpha fetoprotein was within reference range. Liver biopsy was consistent with HEHE, with positive endothelial markers (CD31, CD34, and factor VIII-related antigen). She underwent living related liver transplantation on June 2013 and was discharged after 20 days with normal liver enzymes. Four months later, she presented with diffuse disease recurrence. Liver biopsy confirmed disease recurrence; she received supportive treatment and unfortunately she died 2 weeks later. Conclusion. HEHE can have rapid and aggressive recurrence after liver transplantation.
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