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Arias Rivera AS, Xacur Trabulce A, Brener Chaoul M, De La Rosa Abaroa MA, Padilla Longoria R. Surgical Management of a Giant Inflammatory Hepatocellular Adenoma in a Young Female. Cureus 2024; 16:e62097. [PMID: 38989373 PMCID: PMC11236435 DOI: 10.7759/cureus.62097] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/10/2024] [Indexed: 07/12/2024] Open
Abstract
Hepatocellular adenomas are rare and benign primary neoplasms of phenotypically mature hepatocytes. Our understanding of this pathology has greatly improved due to advances in molecular and anatomic knowledge. This article provides an in-depth review of hepatic adenomas (HCA) while presenting the case of a 20-year-old patient with a giant inflammatory hepatocellular adenoma with an atypical presentation, in whom surgical intervention was performed via right hepatectomy. In the post-surgical course, the patient had an in-hospital stay of three days with no complications. During outpatient monitoring via laboratory tests and imaging at eight months, the patient did not present any trace of recurrence.
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Zhang Z, Ji J, Qiu G, Hou Z, Mi S, Jin Z, Dai Y, Xie Q, Zeng Y, Huang J. Surgical indications for solid hepatic benign tumors: An updated literature review. Biosci Trends 2023; 17:325-334. [PMID: 37599079 DOI: 10.5582/bst.2023.01152] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/22/2023]
Abstract
Hepatic hemangioma, focal nodular hyperplasia, and hepatic adenoma are the most common benign solid liver tumors. However, their surgical indications have been the subject of debate. Minimally invasive liver resection reduces the cost of surgery and may lead to overtreatment of benign liver tumors. Recently, there has been a growing understanding of the etiology, pathogenesis, and natural history of these tumors. Great progress has also been made in imaging. The use of MRI and contrast agents has improved the accuracy of non-invasive diagnosis of these tumors, and especially in the identification of specific molecular subtypes of liver adenoma. These factors have resulted in alterations of surgical indications for these tumors. This article examines recent literature and it discusses the surgical indications for hepatic hemangioma, focal nodular hyperplasia, and hepatic adenoma while summarizing modifications in clinical management.
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Affiliation(s)
- Zhihong Zhang
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, China
| | - Jun Ji
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, China
| | - Guoteng Qiu
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, China
| | - Ziqi Hou
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, China
| | - Shizheng Mi
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, China
| | - Zhaoxing Jin
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, China
| | - Yunlong Dai
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, China
| | - Qingyun Xie
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, China
| | - Yong Zeng
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, China
| | - Jiwei Huang
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, China
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Jackson DG, Koch RL, Pendyal S, Benjamin R, Kishnani PS. Development of hepatocellular adenomas in a patient with glycogen storage disease Ia treated with growth hormone therapy. JIMD Rep 2023; 64:303-311. [PMID: 37701330 PMCID: PMC10494510 DOI: 10.1002/jmd2.12381] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Accepted: 06/30/2023] [Indexed: 09/14/2023] Open
Abstract
Glycogen storage disease Ia (GSD Ia), also known as von Gierke disease, is caused by pathogenic variants in the G6PC1 gene (OMIM 232200) which encodes glucose-6-phosphatase. Deficiency of glucose-6-phosphatase impairs the processes of gluconeogenesis and glycogenolysis by preventing conversion of glucose-6-phosphate to glucose. Clinical features include fasting hypoglycemia, lactic acidosis, hypertriglyceridemia, hyperuricemia, hepatomegaly, and development of hepatocellular adenomas (HCAs) with potential for malignant transformation. Additionally, patients with GSD Ia often exhibit short stature, in some instances due to growth hormone (GH) deficiency. Patients with short stature caused by GH deficiency typically receive GH injections. Here, we review the literature and describe a female with GSD Ia who had short stature, failure of growth progression, and suspected GH deficiency. This patient received GH injections from ages 11 to 14 years under careful monitoring of an endocrinologist and developed HCAs during that time. To date, there is no reported long-term follow up data on patients with GSD Ia who have received GH therapy, and therefore the clinical outcomes post-GH therapy are unclear.
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Affiliation(s)
- David G. Jackson
- Division of Medical Genetics, Department of PediatricsDuke University Medical CenterDurhamNorth CarolinaUSA
| | - Rebecca L. Koch
- Division of Medical Genetics, Department of PediatricsDuke University Medical CenterDurhamNorth CarolinaUSA
| | - Surekha Pendyal
- Division of Medical Genetics, Department of PediatricsDuke University Medical CenterDurhamNorth CarolinaUSA
| | - Robert Benjamin
- Department of EndocrinologyDuke University Medical CenterDurhamNorth CarolinaUSA
| | - Priya S. Kishnani
- Division of Medical Genetics, Department of PediatricsDuke University Medical CenterDurhamNorth CarolinaUSA
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Corallo C, Bell J, Laverty A, Mohsin M, Prasad R, Albazaz R. Suspected focal nodular hyperplasia in male adults: 10-year experience from a large liver centre. Abdom Radiol (NY) 2023; 48:2292-2301. [PMID: 37043025 DOI: 10.1007/s00261-023-03896-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2023] [Revised: 03/20/2023] [Accepted: 03/21/2023] [Indexed: 04/13/2023]
Abstract
PURPOSE Focal nodular hyperplasia (FNH) is commonly found in females of reproductive age. In males, the diagnosis is made more cautiously due to its lower incidence and higher incidence of hepatocellular carcinoma, which can have overlapping imaging features. Follow-up or biopsy is sometimes required. This retrospective study aims to assess management of suspected FNH in male adult patients at our institution over a 10-year period. METHODS Male adults (≥ 18 years) suspected of having FNH from January 2010-June 2020 were identified using a departmental radiology information system search. Data was collected from radiology reports and patient pathway manager. RESULTS Of 342 patients with suspected FNH, 62 were male (18.1%; F:M of 4.5:1). We only included patients investigated and followed up by MRI, total of 57 patients. Median age was 40 years (range 18-74 years). Background liver disease present in 21/57 (36.8%), majority with hepatic steatosis. Average number of lesions per patient 1.7. 22/57 (38.6%) had at least one MRI follow-up using liver-specific contrast with 7 lesions demonstrating variation in size (range growth: -3.27 mm/year to + 4 mm/year). In 7 cases, MRI was not definitive; 6 required biopsy and 1 resection. Only 2/7 demonstrated malignancy. Of the total 57 patients, 6 have deceased and none due to a misdiagnosed or mismanaged hepatic lesion. CONCLUSION FNH is relatively uncommon in males, however, our data suggests that lesions with typical MRI characteristics do not require follow-up and diagnosis can be made confidently, similar to females. Any atypical features should prompt a biopsy.
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Affiliation(s)
- Carmelo Corallo
- Department of Radiology, Leeds Teaching Hospitals NHS Trust, St. James's University Hospital, Beckett Street Harehills, Leeds, LS9 7TF, UK.
| | - Joshua Bell
- Department of Radiology, Leeds Teaching Hospitals NHS Trust, St. James's University Hospital, Beckett Street Harehills, Leeds, LS9 7TF, UK
| | - Adam Laverty
- Department of Radiology, Leeds Teaching Hospitals NHS Trust, St. James's University Hospital, Beckett Street Harehills, Leeds, LS9 7TF, UK
| | - Maryam Mohsin
- Department of Radiology, Leeds Teaching Hospitals NHS Trust, St. James's University Hospital, Beckett Street Harehills, Leeds, LS9 7TF, UK
| | - Raj Prasad
- Department of Hepatobiliary and Transplant Surgery, Leeds Teaching Hospitals NHS Trust, St. James's University Hospital, Leeds, UK
| | - Raneem Albazaz
- Department of Radiology, Leeds Teaching Hospitals NHS Trust, St. James's University Hospital, Beckett Street Harehills, Leeds, LS9 7TF, UK
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Liu X, Espin-Garcia O, Khalvati F, Namdar K, Fischer S, Haider MA, Jhaveri KS. Hepatocellular adenoma subtyping by qualitative MRI features and machine learning algorithm of integrated qualitative and quantitative features: a proof-of-concept study. Clin Radiol 2023:S0009-9260(23)00231-3. [PMID: 37365116 DOI: 10.1016/j.crad.2023.05.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 03/23/2023] [Accepted: 05/24/2023] [Indexed: 06/28/2023]
Abstract
AIM To evaluate hepatocellular adenoma (HCA) subtyping using qualitative magnetic resonance imaging (MRI) features and feasibility of differentiating HCA subtypes using machine learning (ML) of qualitative and quantitative MRI features with histopathology as the reference standard. MATERIALS AND METHODS This retrospective study included 39 histopathologically subtyped HCAs (13 hepatocyte nuclear factor (HNF)-1-alpha mutated [HHCA], 11 inflammatory [IHCA], one beta-catenin-mutated [BHCA], and 14 unclassified [UHCA]) in 36 patients. HCA subtyping by two blinded radiologists using the proposed schema of qualitative MRI features and using the random forest algorithm was compared against histopathology. For quantitative features, 1,409 radiomic features were extracted after segmentation and reduced to 10 principle components. Support vector machine and logistic regression was applied to assess HCA subtyping. RESULTS Qualitative MRI features with proposed flow chart yielded diagnostic accuracies of 87%, 82%, and 74% for HHCA, IHCA, and UHCA respectively. The ML algorithm based on qualitative MRI features showed AUCs (area under the receiver operating characteristic curve [ROC] curve) of 0.846, 0.642, and 0.766 for diagnosing HHCA, IHCA, and UHCA, respectively. Quantitative radiomic features from portal venous and hepatic venous phase MRI demonstrated AUCs of 0.83 and 0.82, with a sensitivity of 72% and a specificity of 85% in predicting HHCA subtype. CONCLUSIONS The proposed schema of integrated qualitative MRI features with ML algorithm provided high accuracy for HCA subtyping while quantitative radiomic features provide value for diagnosis of HHCA. The key qualitative MRI features for differentiating HCA subtypes were concordant between the radiologists and the ML algorithm. These approaches appear promising to better inform clinical management for patients with HCA.
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Affiliation(s)
- X Liu
- Joint Department of Medical Imaging, University Health Network, Sinai Health System, University of Toronto, 585 University Ave., Toronto, ON, M5G 2N2, Canada
| | - O Espin-Garcia
- Department of Biostatistics, Princess Margaret Centre, University Health Network and Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, 610 University Ave, Toronto, ON, M5G 2M9, Canada
| | - F Khalvati
- Diagnostic Imaging, Neurosciences and Mental Health, Research Institute, The Hospital for Sick Children, 555 University Ave., Toronto, ON, M5G 1X8, Canada; Department of Medical Imaging, Institute of Medical Science (IMS), University of Toronto, 555 University Ave., Toronto, ON, M5G 1X8, Canada; Department of Mechanical and Industrial Engineering, University of Toronto, 555 University Ave., Toronto, ON, M5G 1X8, Canada
| | - K Namdar
- The Hospital for Sick Children, Institute of Medical Science, University of Toronto, 555 University Ave., Toronto, ON, M5G 1X8, Canada
| | - S Fischer
- Laboratory Medicine Program, University Health Network, University of Toronto, Laboratory Medicine and Pathobiology, 200 Elizabeth Street, Toronto, ON, M5G 2C4, Canada
| | - M A Haider
- Joint Department of Medical Imaging, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, 585 University Ave., Toronto, ON, M5G 2N2, Canada
| | - K S Jhaveri
- Joint Department of Medical Imaging, University Health Network, Sinai Health System, University of Toronto, 585 University Ave., Toronto, ON, M5G 2N2, Canada.
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Differentiation of focal nodular hyperplasia and hepatocellular adenoma using qualitative and quantitative imaging features and classification and regression tree analysis. Abdom Radiol (NY) 2023; 48:874-885. [PMID: 36528729 DOI: 10.1007/s00261-022-03766-0] [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: 09/21/2022] [Revised: 11/25/2022] [Accepted: 11/26/2022] [Indexed: 12/23/2022]
Abstract
PURPOSE To assess qualitative and quantitative analysis of gadoxetate disodium-enhanced hepatobiliary phase MR imaging (MRI) and assess the performance of classification and regression tree analysis for the differentiation of focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA). MATERIALS AND METHODS This retrospective study was approved by our local ethics committee. One hundred seventy patients suspected of having FNH or HCA underwent gadoxetate disodium-enhanced MRI. The reference standard was either pathology or follow-up imaging. Two readers reviewed images to identify qualitative imaging features and measure signal intensity on unenhanced, dynamic, and hepatobiliary phase images. For quantitative analysis, contrast enhancement ratio (CER), lesion-to-liver contrast (LLC), signal intensity ratio (SIR), and relative signal enhancement ratio (RSER) were calculated. A classification and regression tree (CART) analysis was developed. RESULTS Eighty-five patients met the inclusion criteria, with a total of 97 FNHs and 43 HCAs. For qualitative analysis, the T1 signal intensity on the hepatobiliary phase provided the highest overall classification performance (91.9% sensitivity, 90.1% specificity, and 90.9% accuracy). For quantitative analysis, RSER in the hepatobiliary phase with a threshold of 0.723 provided the highest classification performance (92.6% sensitivity and 89.4% specificity) to differentiate FNHs from HCAs. A CART model based on five qualitative imaging features provided an accuracy of 94.4% (95% confidence interval 90.0-98.9%). CONCLUSION Gadoxetate disodium-enhanced hepatobiliary phase provides high diagnostic performance as demonstrated in quantitative and qualitative analysis in differentiation of FNH and HCA, supported by a CART decision model.
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Schaible J, Schreyer AG, Mehrabi A, Longerich T, Kieser M, Kreimeyer S, Klauss M, Grenacher L. Subtyping of hepatocellular adenomas using Gd-EOB-DTPA: a qualitative and quantitative analysis. Acta Radiol 2023:2841851221149197. [PMID: 36650712 DOI: 10.1177/02841851221149197] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
BACKGROUND The goal of medical imaging is not only to identify the entity "hepatocellular adenoma," but to detect typical magnetic resonance (MR) patterns of the subtypes so that lesions with a higher malignant transformation rate could be differentiated from those that should just be controlled. PURPOSE To evaluate the differentiation between subtypes of hepatocellular adenomas using hepatobiliary specific contrast agent (Gd-EOB-DTPA) in MR imaging. MATERIAL/METHODS A total of 11 patients with 39 lesions with histologically proven hepatocellular adenomas were evaluated. Of the, 34 were inflammatory hepatocellular adenomas (IHCA) and 5 were HNF1α adenomas. No β-catenin-mutated adenoma was found. In all patients, a standard protocol considering the guidelines of the international consensus conference of Gd-EOB-DTPA was performed in a 1.5-T scanner. Besides a qualitative analysis of all sequences, we measured the quantitative signal intensity (SI) ratio in all examinations. RESULTS Qualitative analysis showed that best sequences for differentiation of HNF1α adenomas from IHCA were T1-weighted (T1W) precontrast (P = 0.03) and portalvenous phase (P < 0.0001) as well as arterial phase (P = 0.002). All adenomas were hypointense in hepatobiliary phase (15 min). The quantitative analyses of the SI ratio and of lesion-to-liver contrast (LLC) ratio show statistically significant differences in T1W precontrast (SI: P = 0.035; LLC: P = 0.049) and portalvenous phase (SI: P = 0.002; LLC: P = 0.002). CONCLUSION Subtyping of hepatocellular adenomas using Gd-EOB-DTPA is possible due to qualitative and quantitative analyses regarding T1W precontrast and portalvenous phase. In addition, the SI ratio and liver-to-lesion contrast ratio in the arterial phase gave additional qualitative information for differentiation.
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Affiliation(s)
- Jan Schaible
- Conradia, Diagnostic Imaging and Prevention Center, Munich, Germany
| | - Andreas G Schreyer
- Department of Radiology, University Medical Center Brandenburg an der Havel, Brandenburg, Germany
| | - Arianeb Mehrabi
- Department of Visceral Surgery, University of Heidelberg, Heidelberg, Germany
| | - Thomas Longerich
- Institute of Pathology, University of Heidelberg, Heidelberg, Germany
| | - Meinhard Kieser
- Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany
| | - Sylvia Kreimeyer
- Diagnostic and Interventional Radiology, University of Heidelberg, Heidelberg, Germany
| | - Miriam Klauss
- Diagnostic and Interventional Radiology, University of Heidelberg, Heidelberg, Germany
| | - Lars Grenacher
- Conradia, Diagnostic Imaging and Prevention Center, Munich, Germany.,Diagnostic and Interventional Radiology, University of Heidelberg, Heidelberg, Germany
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Kim TH, Woo S, Ebrahimzadeh S, McInnes MDF, Gerst SR, Do RK. Hepatic Adenoma Subtypes on Hepatobiliary Phase of Gadoxetic Acid-Enhanced MRI: Systematic Review and Meta-Analysis. AJR Am J Roentgenol 2023; 220:28-38. [PMID: 35920706 PMCID: PMC11759479 DOI: 10.2214/ajr.22.27989] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
BACKGROUND. Accumulating evidence indicates that hepatocellular adenoma (HCA) may have a higher frequency of hepatobiliary phase (HBP) iso- or hyperintensity than previously reported. OBJECTIVE. The purpose of this study was to evaluate the proportion of HCA that shows iso- or hyperintensity in the HBP of gadoxetic acid-enhanced MRI, stratified by HCA subtype (HNF1a-inactivated [H-HCA], inflammatory [I-HCA], β-catenin-activated [B-HCA], and unclassified [U-HCA] HCA), and to assess the diagnostic performance of HBP iso- or hyperintensity for differentiating focal nodular hyperplasia (FNH) from HCA. EVIDENCE ACQUISITION. PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched through February 14, 2022, for articles reporting HBP signal intensity on gadoxetic acid-enhanced MRI among pathologically proven HCAs, stratified by subtype. The pooled proportion of HBP iso- or hyperintensity was determined for each subtype and compared using metaregression. Diagnostic performance of HBP iso- or hyperintensity for differentiating FNH from all HCA subtypes combined and from B-HCA and U-HCA combined was assessed using bivariate modeling. EVIDENCE SYNTHESIS. Twenty-eight studies (12 original investigations, 16 case reports or case series) were included, yielding 364 patients with 410 HCAs (112 H-HCAs, 203 I-HCAs, 33 B-HCAs, 62 U-HCAs). Pooled proportion of HBP iso- or hyperintensity was 14% (95% CI, 4-26%) among all HCAs, 0% (95% CI, 0-2%) among H-HCAs, 11% (95% CI, 0-29%) among U-HCAs, 14% (95% CI, 2-31%) among I-HCAs, and 59% (95% CI, 26-88%) among B-HCAs; metaregression showed significant difference among subtypes (p < .001). In four studies reporting diagnostic performance information, HBP iso- or hyperintensity had sensitivity of 99% (95% CI, 57-100%) and specificity of 89% (95% CI, 82-94%) for differentiating FNH from all HCA subtypes and sensitivity of 99% (95% CI, 53-100%) and specificity of 65% (95% CI, 44-80%) for differentiating FNH from B-HCA or U-HCA. CONCLUSION. HCA subtypes other than H-HCA show proportions of HBP iso- or hyperintensity ranging from 11% (U-HCA) to 59% (B-HCA). Low prevalence of B-HCA has contributed to prior reports of high diagnostic performance of HBP iso- or hyperintensity for differentiating FNH from HCA. CLINICAL IMPACT. Radiologists should recognize the low specificity of HBP iso- or hyperintensity on gadoxetic acid-enhanced MRI for differentiating FNH from certain HCA subtypes.
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Affiliation(s)
- Tae-Hyung Kim
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065
| | - Sungmin Woo
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065
| | - Sanam Ebrahimzadeh
- Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada
| | - Matthew D F McInnes
- Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada
- Department of Radiology, Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada
| | - Scott R Gerst
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065
| | - Richard K Do
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065
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Pompili M, Ardito F, Brunetti E, Cabibbo G, Calliada F, Cillo U, de Sio I, Golfieri R, Grova M, Gruttadauria S, Guido M, Iavarone M, Manciulli T, Pagano D, Pettinari I, Santopaolo F, Soresi M, Colli A. Benign liver lesions 2022: Guideline for clinical practice of Associazione Italiana Studio del Fegato (AISF), Società Italiana di Radiologia Medica e Interventistica (SIRM), Società Italiana di Chirurgia (SIC), Società Italiana di Ultrasonologia in Medicina e Biologia (SIUMB), Associazione Italiana di Chirurgia Epatobilio-Pancreatica (AICEP), Società Italiana Trapianti d'Organo (SITO), Società Italiana di Anatomia Patologica e Citologia Diagnostica (SIAPEC-IAP) - Part II - Solid lesions. Dig Liver Dis 2022; 54:1614-1622. [PMID: 36089523 DOI: 10.1016/j.dld.2022.08.031] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Revised: 08/11/2022] [Accepted: 08/18/2022] [Indexed: 12/30/2022]
Abstract
Benign liver lesions are increasingly diagnosed in daily clinical practice due to the growing use of imaging techniques for the study of the abdomen in patients who have non-specific symptoms and do not have an increased risk of hepatic malignancy. They include simple or parasitic hepatic cysts and solid benign tumors which differ widely in terms of prevalence, clinical relevance, symptoms and natural history and often lead to significant clinical problems relating to diagnosis and clinical management. Following the need to have updated guidelines on the management of benign focal liver lesions, the Scientific Societies mainly involved in their management have promoted the drafting of a new dedicated document. This document was drawn up according to the present Italian rules and methodologies necessary to produce clinical, diagnostic, and therapeutic guidelines based on evidence. Here we present the second part of the guideline, concerning the diagnosis and clinical management of hemangioma, focal nodular hyperplasia, and hepatocellular adenoma.
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Affiliation(s)
- Maurizio Pompili
- Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Gemelli, Universitario "A. Gemelli" IRCCS, Università Cattolica del Sacro Cuore, Facoltà di Medicina e Chirurgia, "Agostino Gemelli", Largo A. Gemelli, 8, Roma 00168, Italy.
| | - Francesco Ardito
- Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Gemelli, Universitario "A. Gemelli" IRCCS, Università Cattolica del Sacro Cuore, Facoltà di Medicina e Chirurgia, "Agostino Gemelli", Largo A. Gemelli, 8, Roma 00168, Italy
| | - Enrico Brunetti
- Dipartimento di Scienze Cliniche, Chirurgiche, Diagnostiche e Pediatriche, Università di Pavia. Unità di Malattie Infettive e Immunologia, IRCCS Fondazione Ospedale San Matteo, Pavia, Italy
| | - Giuseppe Cabibbo
- Sezione di Gastroenterologia e Epatologia, Dipartimento di Promozione della Salute, Materno-Infantile, di Medicina Interna e Specialistica di Eccellenza "G. D'Alessandro" (PROMISE) Università di Palermo, Italy
| | - Fabrizio Calliada
- Dipartimento di Radiologia, Fondazione Policlinico San Matteo IRCCS, Università di Pavia, Italy
| | - Umberto Cillo
- Chirurgia Epatobiliare e Trapianto di Fegato, Ospedale Universitario di Padova, Italy
| | - Ilario de Sio
- Epatogastroenterologia, Università della Campania Luigi Vanvitelli, Facoltà di Medicina e Chirurgia, Napoli, Italy
| | - Rita Golfieri
- Dipartimento di Radiologia, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy
| | - Mauro Grova
- Sezione di Gastroenterologia e Epatologia, Dipartimento di Promozione della Salute, Materno-Infantile, di Medicina Interna e Specialistica di Eccellenza "G. D'Alessandro" (PROMISE) Università di Palermo, Italy
| | - Salvatore Gruttadauria
- Dipartimento per la cura e lo studio delle Patologie Addominali e dei Trapianti Addominali, Dipartimento di Chirurgia e Specialità Medico-Chirurgiche, IRCCS-ISMETT-UPMCI, Palermo, Università di Catania, Italy
| | - Maria Guido
- Dipartimento di Anatomia Patologica, Azienda ULSS2 Marca Trevigiana, Treviso, Italy; Dipartimento di Medicina - DIMED, Università di Padova, Italy
| | - Massimo Iavarone
- Divisione di Gastroenterologia ed Epatologia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy
| | - Tommaso Manciulli
- Dipartimento di Medicina Sperimentale e Clinica - Università degli Studi, Firenze, Italy
| | - Duilio Pagano
- Dipartimento per la cura e lo studio delle Patologie Addominali e dei Trapianti Addominali, IRCCS-ISMETT-UPMC, Palermo, Italy
| | - Irene Pettinari
- Dipartimento di Radiologia, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy
| | - Francesco Santopaolo
- Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Gemelli, Universitario "A. Gemelli" IRCCS, Università Cattolica del Sacro Cuore, Facoltà di Medicina e Chirurgia, "Agostino Gemelli", Largo A. Gemelli, 8, Roma 00168, Italy
| | - Maurizio Soresi
- Medicina Interna, Dipartimento di Promozione della Salute, Materno-Infantile, di Medicina Interna e Specialistica di Eccellenza "G. D'Alessandro" (PROMISE) Università di Palermo, Italy
| | - Agostino Colli
- Dipartimento di Medicina Trasfusionale ed Ematologia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy
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10
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Nault JC, Paradis V, Ronot M, Zucman-Rossi J. Benign liver tumours: understanding molecular physiology to adapt clinical management. Nat Rev Gastroenterol Hepatol 2022; 19:703-716. [PMID: 35835851 DOI: 10.1038/s41575-022-00643-5] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/01/2022] [Indexed: 12/08/2022]
Abstract
Improvements in understanding the pathophysiology of the different benign liver nodules have refined their nosological classification. New criteria have been identified using imaging, histology and molecular analyses for a precise diagnosis of these tumours. Improvement in the classification of liver tumours provides a more accurate prediction of disease progression and has modified patient management. Haemangioma and focal nodular hyperplasia, the most common benign liver tumours that develop in the absence of chronic liver disease, are usually easy to diagnose on imaging and do not require specific treatment. However, hepatocellular adenomas and cirrhotic macronodules can be difficult to discriminate from hepatocellular carcinoma. The molecular subtyping of hepatocellular adenomas in five major subgroups defined by HNF1A inactivation, β-catenin mutation in exon 3 or exon 7/8, and activation of inflammatory or Hedgehog pathways helps to identify the tumours at risk of malignant transformation or bleeding. New clinical, biological and molecular tools have gradually been included in diagnostic and treatment algorithms to classify benign liver tumours and improve patient management. This Review aims to explain the main pathogenic mechanisms of benign liver tumours and how this knowledge could influence clinical practice.
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Affiliation(s)
- Jean-Charles Nault
- Service d'hépatologie, Hôpital Avicenne, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, Bobigny, France. .,Unité de Formation et de Recherche Santé Médecine et Biologie Humaine, Université Paris Nord, Communauté d'Universités et Etablissements Sorbonne Paris Cité, Paris, France. .,Centre de Recherche des Cordeliers, Sorbonne Université, Inserm, Université de Paris Cité, team «Functional Genomics of Solid Tumors», Paris, France. .,Equipe labellisée Ligue Nationale Contre le Cancer, Labex OncoImmunology, Paris, France.
| | - Valérie Paradis
- Service de Pathologie, Hôpital Beaujon, AP-HP Nord, Clichy, France.,Université de Paris, INSERM U1149 "Centre de Recherche sur l'inflammation", CRI, Paris, France
| | - Maxime Ronot
- Université de Paris, INSERM U1149 "Centre de Recherche sur l'inflammation", CRI, Paris, France.,Department of Radiology, Assistance-Publique Hôpitaux de Paris, Hôpital Beaujon, AP-HP Nord, Clichy, France
| | - Jessica Zucman-Rossi
- Centre de Recherche des Cordeliers, Sorbonne Université, Inserm, Université de Paris Cité, team «Functional Genomics of Solid Tumors», Paris, France. .,Equipe labellisée Ligue Nationale Contre le Cancer, Labex OncoImmunology, Paris, France. .,Hôpital Européen Georges Pompidou, APHP, Paris, France.
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11
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Focal Benign Liver Lesions and Their Diagnostic Pitfalls. Radiol Clin North Am 2022; 60:755-773. [DOI: 10.1016/j.rcl.2022.05.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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12
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Reizine E, Meurgey A, Amaddeo G, Laurent A, Calderaro J, Mule S, Luciani A. Fat in mass in primary liver lesions: are usual MRI diagnostic criteria of both malignant and benign liver lesions still applicable? Abdom Radiol (NY) 2022; 47:2347-2355. [PMID: 35672475 DOI: 10.1007/s00261-022-03561-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Revised: 05/15/2022] [Accepted: 05/17/2022] [Indexed: 11/01/2022]
Abstract
PURPOSE To evaluate the accuracy of the usual MRI diagnostic patterns of primary liver lesions applied to the diagnosis of pathologically proven fat-containing liver lesions. MATERIALS AND METHODS This monocentric IRB approved retrospective study included all patients with pathologically proven focal liver lesions and documented intra-tumoral fat on pathology and who underwent preoperative liver MRI for characterization. Both liver morphology and usual lesion MRI features were analyzed and their distribution correlated to the final pathological result (Khi-2 or Fisher exact tests, Student t-test or Mann-Whitney U test, as appropriate). The Sensitivity (Se) and Specificity (Sp) of MRI patterns known to be associated to both Hepatocellular Carcinoma (HCC), Focal Nodular Hyperplasia (FNH), and Hepatocellular Adenoma (HCA) subtypes were evaluated. RESULTS Between March 2014 and November 2021, 66 lesions were included, corresponding to: 26 HCC, 32 HCA, 6 FNH and 2 hepatic angiomyolipoma (HAML). All lesions developed on a dysmorphic liver were HCC. A non-rim arterial phase hyperenhancement with a washout and an enhancing capsule had a 98% specificity for HCC diagnosis; A homogeneous dropout of signal on the opposed phase had a sensitivity of 92% and a specificity of 89% for the diagnosis of HNF1alpha inactivated subtype of HCA (HHCA). The FNH pattern was specific at 100% for the diagnosis of FNH with a 40% Se. Finally, the accuracy of inflammatory hepatocellular adenoma (IHCA) pattern had a low 60% Se but a high 89% Sp for IHCA diagnosis. CONCLUSION Known MRI patterns remain reliable for the accurate diagnosis of primary liver tumors on MRI even in fat-containing lesions.
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Affiliation(s)
- Edouard Reizine
- Department of Radiology, APHP, HU Henri Mondor, Creteil, Val-de-Marne, France.
- Faculté de Médecine, Universite Paris Est Creteil, 94010, Creteil, France.
- INSERM Unit U 955, Equipe 18, 94010, Creteil, France.
| | - Azure Meurgey
- Department of Radiology, APHP, HU Henri Mondor, Creteil, Val-de-Marne, France
| | - Giuliana Amaddeo
- INSERM Unit U 955, Equipe 18, 94010, Creteil, France
- Department of Hepatology, APHP, HU Henri Mondor, Créteil, France
| | - Alexis Laurent
- INSERM Unit U 955, Equipe 18, 94010, Creteil, France
- Departement of Liver Surgery, APHP, HU Henri Mondor, Creteil, Val-de-Marne, France
| | - Julien Calderaro
- INSERM Unit U 955, Equipe 18, 94010, Creteil, France
- Department of Pathology, APHP, HU Henri Mondor, Creteil, Val-de-Marne, France
| | - Sebastien Mule
- Department of Radiology, APHP, HU Henri Mondor, Creteil, Val-de-Marne, France
- Faculté de Médecine, Universite Paris Est Creteil, 94010, Creteil, France
- INSERM Unit U 955, Equipe 18, 94010, Creteil, France
| | - Alain Luciani
- Department of Radiology, APHP, HU Henri Mondor, Creteil, Val-de-Marne, France
- Faculté de Médecine, Universite Paris Est Creteil, 94010, Creteil, France
- INSERM Unit U 955, Equipe 18, 94010, Creteil, France
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13
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Gatti M, Maino C, Tore D, Carisio A, Darvizeh F, Tricarico E, Inchingolo R, Ippolito D, Faletti R. Benign focal liver lesions: The role of magnetic resonance imaging. World J Hepatol 2022; 14:923-943. [PMID: 35721295 PMCID: PMC9157713 DOI: 10.4254/wjh.v14.i5.923] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2021] [Revised: 08/07/2021] [Accepted: 04/09/2022] [Indexed: 02/06/2023] Open
Abstract
Liver lesions are common findings in radiologists’ daily routine. They are a complex category of pathology that range from solitary benign lesions to primary liver cancer and liver metastases. Benign focal liver lesions can arise from different liver cell types: Epithelial (hepatocytes and biliary cells) and nonepithelial (mesenchymal cells). Liver magnetic resonance imaging (MRI) is a fundamental radiological method in these patients as it allows with its multiparametric approach optimal non-invasive tissue characterization. Furthermore, advanced liver MRI techniques such as diffusion-weighted imaging and hepatobiliary contrast agents have improved the detection of focal liver lesions and can be highly effective in differentiating pseudotumor from tumors, as well as benign from malignant lesions, and can also be used for differential diagnosis. Although histological examination can be useful in making a definitive diagnosis, MRI is an important modality in the diagnosis of liver lesions with a significant impact on patient care. This aim of this review is to provide a comprehensive overview of benign liver lesions on MRI.
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Affiliation(s)
- Marco Gatti
- Department of Surgical Sciences, University of Turin, Turin 10126, Italy
| | - Cesare Maino
- Department of Diagnostic Radiology, Ospedale San Gerardo, Monza 20900, Italy
| | - Davide Tore
- Department of Surgical Sciences, University of Turin, Turin 10126, Italy
| | - Andrea Carisio
- Department of Surgical Sciences, University of Turin, Turin 10126, Italy
| | - Fatemeh Darvizeh
- School of Medicine, Vita-Salute San Raffaele University, Milan 20121, Japan
| | | | - Riccardo Inchingolo
- Interventional Radiology Unit, “F. Miulli” Regional General Hospital, Acquaviva delle Fonti 70021, Italy
| | - Davide Ippolito
- Department of Diagnostic Radiology, School of Medicine, University of Milano-Bicocca, Monza 20900, Italy
- Department of Diagnostic Radiology, Ospedale San Gerardo, Monza 20900, Italy
| | - Riccardo Faletti
- Department of Surgical Sciences, University of Turin, Turin 10126, Italy
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14
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Michallek F, Sartoris R, Beaufrère A, Dioguardi Burgio M, Cauchy F, Cannella R, Paradis V, Ronot M, Dewey M, Vilgrain V. Differentiation of hepatocellular adenoma by subtype and hepatocellular carcinoma in non-cirrhotic liver by fractal analysis of perfusion MRI. Insights Imaging 2022; 13:81. [PMID: 35482151 PMCID: PMC9050986 DOI: 10.1186/s13244-022-01223-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Accepted: 04/08/2022] [Indexed: 11/30/2022] Open
Abstract
Background To investigate whether fractal analysis of perfusion differentiates hepatocellular adenoma (HCA) subtypes and hepatocellular carcinoma (HCC) in non-cirrhotic liver by quantifying perfusion chaos using four-dimensional dynamic contrast-enhanced magnetic resonance imaging (4D-DCE-MRI). Results A retrospective population of 63 patients (47 female) with histopathologically characterized HCA and HCC in non-cirrhotic livers was investigated. Our population consisted of 13 hepatocyte nuclear factor (HNF)-1α-inactivated (H-HCAs), 7 β-catenin-exon-3-mutated (bex3-HCAs), 27 inflammatory HCAs (I-HCAs), and 16 HCCs. Four-dimensional fractal analysis was applied to arterial, portal venous, and delayed phases of 4D-DCE-MRI and was performed in lesions as well as remote liver tissue. Diagnostic accuracy of fractal analysis was compared to qualitative MRI features alone and their combination using multi-class diagnostic accuracy testing including kappa-statistics and area under the receiver operating characteristic curve (AUC). Fractal analysis allowed quantification of perfusion chaos, which was significantly different between lesion subtypes (multi-class AUC = 0.90, p < 0.001), except between I-HCA and HCC. Qualitative MRI features alone did not allow reliable differentiation between HCA subtypes and HCC (κ = 0.35). However, combining qualitative MRI features and fractal analysis reliably predicted the histopathological diagnosis (κ = 0.89) and improved differentiation of high-risk lesions (i.e., HCCs, bex3-HCAs) and low-risk lesions (H-HCAs, I-HCAs) from sensitivity and specificity of 43% (95% confidence interval [CI] 23–66%) and 47% (CI 32–64%) for qualitative MRI features to 96% (CI 78–100%) and 68% (CI 51–81%), respectively, when adding fractal analysis. Conclusions Combining qualitative MRI features with fractal analysis allows identification of HCA subtypes and HCCs in patients with non-cirrhotic livers and improves differentiation of lesions with high and low risk for malignant transformation. Supplementary Information The online version contains supplementary material available at 10.1186/s13244-022-01223-6.
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Affiliation(s)
- Florian Michallek
- Department of Radiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117, Berlin, Germany.
| | - Riccardo Sartoris
- Université de Paris, CRI, U1149, Paris, France.,Department of Radiology, Hôpital Beaujon, AP-HP.Nord, 100 Boulevard du Général Leclerc, 92110, Clichy, France
| | - Aurélie Beaufrère
- Université de Paris, CRI, U1149, Paris, France.,Department of Pathology, Hôpital Beaujon, AP-HP.Nord, 100 Boulevard du Général Leclerc, 92110, Clichy, France
| | - Marco Dioguardi Burgio
- Université de Paris, CRI, U1149, Paris, France.,Department of Radiology, Hôpital Beaujon, AP-HP.Nord, 100 Boulevard du Général Leclerc, 92110, Clichy, France
| | - François Cauchy
- Department of HBP Surgery, Hôpital Beaujon, AP-HP.Nord, 100 Boulevard du Général Leclerc, 92110, Clichy, France
| | - Roberto Cannella
- Department of Radiology, Hôpital Beaujon, AP-HP.Nord, 100 Boulevard du Général Leclerc, 92110, Clichy, France.,Section of Radiology - BiND, University Hospital "Paolo Giaccone", Via del Vespro 129, 90127, Palermo, Italy.,Department of Health Promotion Sciences Maternal and Infant Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, 90127, Palermo, Italy
| | - Valérie Paradis
- Department of Pathology, Hôpital Beaujon, AP-HP.Nord, 100 Boulevard du Général Leclerc, 92110, Clichy, France
| | - Maxime Ronot
- Université de Paris, CRI, U1149, Paris, France.,Department of Radiology, Hôpital Beaujon, AP-HP.Nord, 100 Boulevard du Général Leclerc, 92110, Clichy, France
| | - Marc Dewey
- Department of Radiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117, Berlin, Germany.,DKTK (German Cancer Consortium), Partner Site, Berlin, Germany
| | - Valérie Vilgrain
- Université de Paris, CRI, U1149, Paris, France.,Department of Radiology, Hôpital Beaujon, AP-HP.Nord, 100 Boulevard du Général Leclerc, 92110, Clichy, France
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15
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Aziz H, Brown ZJ, Eskander MF, Aquina CT, Baghdadi A, Kamel IR, Pawlik TM. A Scoping Review of the Classification, Diagnosis, and Management of Hepatic Adenomas. J Gastrointest Surg 2022; 26:965-978. [PMID: 35083725 DOI: 10.1007/s11605-022-05246-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Accepted: 01/05/2022] [Indexed: 01/31/2023]
Abstract
BACKGROUND Hepatic adenomas (HA), or hepatocellular adenomas, are benign, solid liver lesions that develop in otherwise normal livers, often in the setting of increased estrogen levels. While considered a benign tumor, there is a risk for substantial complications such as hemorrhage and malignant transformation. We review the diagnosis, classification, and potential therapeutic management options for patients with HA. METHODS A scoping narrative review was conducted based on recent literature regarding classification, diagnosis, and management of HA. RESULTS While HAs are typically considered benign, complications such as hemorrhage and malignant transformation may occur in approximately 25% and 5% of patients, respectively. Recent advances in imaging and molecular profiling have allowed for the classification of HAs into subtypes allowing for patient risk stratification that helps guide management. Surgical resection should be considered in asymptomatic patients who are male, have an adenoma ≥5 cm in diameter, or have the β-catenin-activated subtype due to an increased risk of hemorrhage and/or malignant transformation. CONCLUSION Molecular profiling has aided in the stratification of patients relative to the risk of complications to predict better the potential behavior of HAs.
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Affiliation(s)
- Hassan Aziz
- Department of Surgery, Tufts University School of Medicine, Boston, MA, USA
| | - Zachary J Brown
- Department of Surgery, The Ohio State University Wexner Medical Center, 395 W. 12th Ave., Suite, Columbus, OH, 670, USA
| | - Mariam F Eskander
- Department of Surgery, The Ohio State University Wexner Medical Center, 395 W. 12th Ave., Suite, Columbus, OH, 670, USA
| | - Christopher T Aquina
- Department of Surgery, The Ohio State University Wexner Medical Center, 395 W. 12th Ave., Suite, Columbus, OH, 670, USA
| | | | - Ihab R Kamel
- Department of Radiology, Johns Hopkins University, Baltimore, MD, USA
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center, 395 W. 12th Ave., Suite, Columbus, OH, 670, USA.
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16
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Chopinet S, Beaufrère A, Soubrane O, Cauchy F, Paradis V. Reply to: "Malignant transformation of hepatocellular adenoma". JHEP Rep 2022; 4:100429. [PMID: 35141512 PMCID: PMC8810563 DOI: 10.1016/j.jhepr.2022.100429] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Revised: 12/17/2021] [Accepted: 12/20/2021] [Indexed: 11/16/2022] Open
Affiliation(s)
- Sophie Chopinet
- Department of HPB and Liver transplantation, Assistance Publique-Hôpitaux de Paris and Université de Paris, Hôpital Beaujon, Clichy, France
| | - Aurélie Beaufrère
- Department of pathology, Assistance Publique-Hôpitaux de Paris and Université de Paris, Hôpital Beaujon, Clichy, France
| | - Olivier Soubrane
- Department of HPB and Liver transplantation, Assistance Publique-Hôpitaux de Paris and Université de Paris, Hôpital Beaujon, Clichy, France
| | - François Cauchy
- Department of HPB and Liver transplantation, Assistance Publique-Hôpitaux de Paris and Université de Paris, Hôpital Beaujon, Clichy, France
| | - Valérie Paradis
- Department of pathology, Assistance Publique-Hôpitaux de Paris and Université de Paris, Hôpital Beaujon, Clichy, France
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17
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Desjonqueres E, Campani C, Marra F, Zucman-Rossi J, Nault JC. Preneoplastic lesions in the liver: Molecular insights and relevance for clinical practice. Liver Int 2022; 42:492-506. [PMID: 34982503 DOI: 10.1111/liv.15152] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2021] [Revised: 12/20/2021] [Accepted: 12/22/2021] [Indexed: 12/12/2022]
Abstract
Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) are the most frequent primary liver cancers, accounting for approximately 80% and 15%, respectively. HCC carcinogenesis occurs mostly in cirrhosis and is a complex multi-step process, from precancerous lesions (low-grade and high-grade dysplastic nodules) to progressed HCC. During the different stages of liver carcinogenesis, there is an accumulation of pathological, genetic and epigenetic changes leading to initiation, malignant transformation and finally tumour progression. In contrast, a small subset of HCC occurs in normal liver from the transformation of hepatocellular adenoma (HCA), a benign hepatocellular tumour. The recent molecular classification enables to stratify HCAs according to their risk of complication, in particular malignant transformation, associated with mutations in exon 3 of the catenin beta 1 (CTNNB1) gene. Cholangiocarcinoma (CCA) derives from the multistep malignant transformation of preneoplastic lesions, like biliary intraepithelial neoplasia (BilIN) and intraductal papillary neoplasm of the bile duct (IPNB), for which a pre-operative diagnosis remains difficult. Different genetic alterations are involved in BilIN and IPNB progression, leading to the development of tubular or intestinal adenocarcinoma. The aims of this review are to describe the main clinical and molecular features of preneoplastic lesions leading to the development of HCC and CCA, their implications in clinical practice and the perspectives for future research.
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Affiliation(s)
- Elvire Desjonqueres
- Service d'hépatologie, Hôpital Avicenne, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, Bobigny, France.,Unité de Formation et de Recherche Santé Médecine et Biologie Humaine, Université Paris 13, Communauté d'Universités et Etablissements Sorbonne Paris Cité, Paris, France.,Centre de Recherche des Cordeliers, Sorbonne Université, Inserm, Université de Paris, team « Functional Genomics of Solid Tumors », Paris, France.,Equipe labellisée Ligue Nationale Contre le Cancer, Labex OncoImmunology, Paris, France
| | - Claudia Campani
- Unité de Formation et de Recherche Santé Médecine et Biologie Humaine, Université Paris 13, Communauté d'Universités et Etablissements Sorbonne Paris Cité, Paris, France.,Centre de Recherche des Cordeliers, Sorbonne Université, Inserm, Université de Paris, team « Functional Genomics of Solid Tumors », Paris, France.,Equipe labellisée Ligue Nationale Contre le Cancer, Labex OncoImmunology, Paris, France.,Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Fabio Marra
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Jessica Zucman-Rossi
- Centre de Recherche des Cordeliers, Sorbonne Université, Inserm, Université de Paris, team « Functional Genomics of Solid Tumors », Paris, France.,Equipe labellisée Ligue Nationale Contre le Cancer, Labex OncoImmunology, Paris, France.,Hôpital Européen Georges Pompidou, APHP, Paris, France
| | - Jean-Charles Nault
- Service d'hépatologie, Hôpital Avicenne, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, Bobigny, France.,Unité de Formation et de Recherche Santé Médecine et Biologie Humaine, Université Paris 13, Communauté d'Universités et Etablissements Sorbonne Paris Cité, Paris, France.,Centre de Recherche des Cordeliers, Sorbonne Université, Inserm, Université de Paris, team « Functional Genomics of Solid Tumors », Paris, France.,Equipe labellisée Ligue Nationale Contre le Cancer, Labex OncoImmunology, Paris, France
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18
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Ziogas IA, Tasoudis PT, Serifis N, Alexopoulos SP, Montenovo MI, Shingina A. Liver Transplantation for Hepatic Adenoma: A UNOS Database Analysis and Systematic Review of the Literature. Transplant Direct 2022; 8:e1264. [PMID: 35018302 PMCID: PMC8735769 DOI: 10.1097/txd.0000000000001264] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Revised: 10/01/2021] [Accepted: 10/25/2021] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Liver transplantation (LT) has been employed for hepatic adenoma (HA) on a case-oriented basis. We aimed to describe the characteristics, waitlist, and post-LT outcomes of patients requiring LT for HA. METHODS All patients listed or transplanted for HA in the United States were identified in the United Network for Organ Sharing (UNOS) database (1987-2020). A systematic literature review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement. RESULTS A total of 199 HA patients were listed for LT in UNOS and the crude waitlist mortality was 9.0%. A total of 142 HA patients underwent LT; 118 of these were among those listed with an indication of HA who underwent LT, and 24 were diagnosed incidentally. Most did not experience hepatocellular carcinoma transformation (89.4%). Over a median follow-up of 62.9 mo, death was reported in 18.3%. The 1-, 3-, and 5-y patient survival rates were 94.2%, 89.7%, and 86.3% in the UNOS cohort. The systematic review yielded 61 articles reporting on 99 nonoverlapping patients undergoing LT for HA and 2 articles reporting on multicenter studies. The most common LT indications were suspected malignancy (39.7%), unresectable HA (31.7%), and increasing size (27.0%), whereas 53.1% had glycogen storage disease. Over a median follow-up of 36.5 mo, death was reported in 6.0% (n=5/84). The 1-, 3-, and 5-y patient survival rates were all 95.0% in the systematic review. CONCLUSIONS LT for HA can lead to excellent long-term outcomes in well-selected patients. Prospective granular data are needed to develop more optimal selection criteria and further improve outcomes.
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Affiliation(s)
- Ioannis A. Ziogas
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Vanderbilt University Medical Center, Nashville, TN
- Surgery Working Group, Society of Junior Doctors, Athens, Greece
| | - Panagiotis T. Tasoudis
- Surgery Working Group, Society of Junior Doctors, Athens, Greece
- School of Health Sciences, University of Thessaly, Larissa, Greece
| | - Nikolaos Serifis
- Surgery Working Group, Society of Junior Doctors, Athens, Greece
- Division of Transplantation, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Sophoclis P. Alexopoulos
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Vanderbilt University Medical Center, Nashville, TN
| | - Martin I. Montenovo
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Vanderbilt University Medical Center, Nashville, TN
| | - Alexandra Shingina
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN
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19
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Nault JC, Blanc JF, Moga L, Calderaro J, Dao T, Guiu B, Hocquelet A, Paradis V, Salamé E, de Lédinghen V, Bourlière M, Bureau C, Ganne-Carrié N. Non-invasive diagnosis and follow-up of benign liver tumours. Clin Res Hepatol Gastroenterol 2022; 46:101765. [PMID: 34333196 DOI: 10.1016/j.clinre.2021.101765] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2021] [Accepted: 07/23/2021] [Indexed: 02/04/2023]
Abstract
Hepatocellular benign liver tumours are mainly developed on normal liver and include hepatic hemangioma, focal nodular hyperplasia and hepatocellular adenoma from the most frequent to the less frequent. The diagnosis of hepatic hemangioma and of simple hepatic biliary cysts can be performed using non-invasive criteria using liver ultrasonography or contrast enhanced MRI. Most of the time the diagnosis of focal nodular hyperplasia can be achieved using contrast-enhanced ultrasonography or contrast enhanced MRI with an additional value of hepatobiliary contrast-agent in this setting. Rarely, if a doubt persists, a tumour and non-tumour liver biopsy can be required in order to establish the diagnosis. As hepatic hemangioma, simple hepatic biliary cysts and focal nodular hyperplasia are not associated with complications, they don't require any treatments or follow-up. Hepatocellular adenomas are mainly diagnosed at histology on surgical samples or liver biopsy even if some radiological features are highly suggestive of several subtypes of hepatocellular adenomas. Finally, the management of hepatocellular adenomas should be guided according to the tumour size, gender but also to the molecular subtypes.
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Affiliation(s)
- Jean-Charles Nault
- Service d'hépatologie, Hôpital Avicenne, APHP; Université Sorbonne Paris Nord, Bobigny & INSERM UMR 1138, Centre de Recherche des Cordeliers, Université de Paris France.
| | - Jean-Frédéric Blanc
- Service d'hépato-gastroentérologie et d'oncologie digestive, Hôpital Haut-Lévêque, CHU Bordeaux, Pessac & INSERM U1053, Université de Bordeaux, Bordeaux France
| | - Lucile Moga
- Service d'Hépatologie et Transplantation Hépatique, Hôpital Beaujon, APHP, Clichy France
| | - Julien Calderaro
- Service de département de pathologie, Hôpital Henri-Mondor, APHP, Créteil France
| | - Thông Dao
- Service d'hépato-gastro-entérologie et nutrition, CHU Caen Normandie, Caen France
| | - Boris Guiu
- Service de radiologie diagnostique et interventionnelle Saint Eloi, CHU Montpellier, Montpellier France
| | - Arnaud Hocquelet
- Service de radiodiagnostic et radiologie interventionnelle, CHUV Lausanne, Lausanne Switzerland
| | | | - Ephrem Salamé
- Unité de Chirurgie Digestive Endocrinienne et Bariatrique, CHU Tours, Tours France
| | - Victor de Lédinghen
- Service d'hépato-gastroentérologie et d'oncologie digestive, Hôpital Haut-Lévêque, CHU Bordeaux, Pessac & INSERM U1053, Université de Bordeaux, Bordeaux France
| | - Marc Bourlière
- Service d'hépato-gastroentérologie, Hôpital Saint Joseph & INSERM UMR 1252 IRD SESSTIM Aix Marseille Université, Marseille
| | - Christophe Bureau
- Service d'hépatologie, Hôpital Rangueil, CHU Toulouse, Toulouse France
| | - Nathalie Ganne-Carrié
- Service d'hépatologie, Hôpital Avicenne, APHP; Université Sorbonne Paris Nord, Bobigny & INSERM UMR 1138, Centre de Recherche des Cordeliers, Université de Paris France
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20
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Paradis V, Beaufrère A. Regenerative Nodules and Liver Tumors in Vascular Liver Diseases. VASCULAR DISORDERS OF THE LIVER 2022:215-236. [DOI: 10.1007/978-3-030-82988-9_14] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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21
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Bioulac-Sage P, Gouw ASH, Balabaud C, Sempoux C. Hepatocellular Adenoma: What We Know, What We Do Not Know, and Why It Matters. Histopathology 2021; 80:878-897. [PMID: 34856012 DOI: 10.1111/his.14605] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Revised: 11/21/2021] [Accepted: 11/25/2021] [Indexed: 11/27/2022]
Abstract
In the last 2 decades there has been significant progress in research and diagnosis of hepatocellular adenoma (HCA), resulting in the establishment of a molecular and immunohistological HCA classification. This review aims to fine-tune the current expertise in order to enhance the histopathological diagnostic possibilities, by refining issues that are already known, addressing diagnostic difficulties and identifying still unknown aspects of HCA. We will discuss novel methods to identify HCA subtypes, in particular the sonic hedgehog HCAs and the interpretation of glutamine synthetase patterns for the recognition of beta-catenin mutated HCAs. The major complications of HCAs, bleeding and malignant transformation, will be considered, including the dilemmas of atypical and borderline lesions. Paragraphs on HCAs in different clinical and geographical settings, e.g. pregnancy, cirrhosis and non-western countries are included. The natural history of the different HCA subtypes in relation with age, sex and risk factors is a feature still insufficiently investigated. This is also true for the risks of clinical bleeding and malignant transformation in association with HCA subtypes. As HCA is a relatively rare tumor, a multicenter and multidisciplinary approach across geographical boundaries will be the appropriate method to establish prospective programs to identify, classify and manage HCAs, focusing on several aspects, e.g. etiology, underlying liver disease, complications, regression and growth. Updating what we know, identifying and addressing features that we do not know matters to warrant optimal patient management.
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Affiliation(s)
| | - Annette S H Gouw
- Departement of Pathology and Medical Biology, University Medical Center Groningen, Groningen, the Netherlands
| | | | - Christine Sempoux
- Service of Clinical Pathology, Institute of Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
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22
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Jusufi MS, Habbel VSA, Oldhafer KJ. Chirurgie bei gutartigen soliden Lebertumoren. TUMORDIAGNOSTIK & THERAPIE 2021; 42:599-608. [DOI: 10.1055/a-1593-7868] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
ZusammenfassungDiese Übersicht konzentriert sich auf die 3 häufigsten gutartigen Lebertumoren – hepatische Hämangiome, fokale noduläre Hyperplasien und hepatozelluläre Adenome – und bietet einen Überblick über die klinischen Präsentationen, das diagnostische Vorgehen, das konservative Management sowie die interventionelle und chirurgische Behandlung.
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Affiliation(s)
| | | | - Karl J. Oldhafer
- Asklepios Campus Hamburg, Medizinische Fakultät der Semmelweis Universität, Hamburg, Germany
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23
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Chopinet S, Cauchy F, Hobeika C, Beaufrère A, Poté N, Farges O, Dokmak S, Bouattour M, Ronot M, Vilgrain V, Paradis V, Soubrane O. Long-term outcomes following resection of hepatocellular adenomas with small foci of malignant transformation or malignant adenomas. JHEP Rep 2021; 3:100326. [PMID: 34368664 PMCID: PMC8326806 DOI: 10.1016/j.jhepr.2021.100326] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Revised: 05/12/2021] [Accepted: 06/11/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND & AIMS Malignant transformation of hepatocellular adenoma (MT-HCA) may occur in up to 5% of tumours. However, the prognostic value of this event remains poorly described. In this study, we aimed to analyse the long-term outcomes of patients undergoing liver resection (LR) for MT-HCA compared to those of patients resected for hepatocellular carcinoma (HCC) occurring on normal liver parenchyma (NP-HCC). METHODS This single-centre retrospective study included all patients who underwent LR for MT-HCA at Beaujon Hospital between 2001 and 2019. MT-HCAs were classified as small foci of malignant transformation HCA (SF-HCA) and as malignant HCA (M-HCA) in cases of predominant HCC foci. Recurrence-free survival (RFS) of MT-HCA was compared with that of NP-HCC after propensity score matching. RESULTS Forty patients (24 men, 16 women) underwent LR for MT-HCA, including 23 with SF-HCA and 17 with M-HCA. Of these cases, 16/40 (40%) had β-catenin mutations, 19/40 (47.5%) were inflammatory, 1 was HNF1α-mutated HCA and 4 (10%) were unclassified HCA. Microvascular invasion (12% vs. 0%, p = 0.091) and satellite nodules (25% vs. 4%, p = 0.028) were more frequently observed in M-HCA than in SF-HCA. After a median follow-up of 67 months, 10 (25%) patients with MT-HCA had tumour recurrence, including 9 with M-HCA and 1 with SF-HCA (p = 0.007). M-HCA was linked to significantly poorer 1-, 3-, 5- and 10-year RFS rates than SF-HCA (76%, 63%, 39%, 37% vs. 100%, 100%, 100%, 91%, p = 0.003). Multivariate analysis showed that SF-HCA was independently associated with improved RFS (hazard ratio 0.064; 95% CI 0.008-0.519; p = 0.01). After propensity score matching, NP-HCC was associated with significantly poorer 1-, 3-, 5- and 10-year RFS rates than MT-HCA (p = 0.01). CONCLUSIONS HCA with malignant transformation yields a better long-term prognosis than NP-HCC. Among MT-HCA, SF-HCA is associated with a better prognosis than M-HCA. LAY SUMMARY The prognostic relevance of malignant transformation of hepatocellular adenoma (HCA) remains unknown. Thus, the aim of our study was to compare the outcomes of patients undergoing liver resection for malignant transformation to those of patients undergoing liver resection for hepatocellular carcinoma (HCC). The main long-term risk after resection for carcinoma is recurrence. In this study, 10/40 patients with malignant transformation of HCA relapsed after resection and we identified age >55 years, presence of satellite nodes, and microvascular invasion as risk factors for long-term recurrence. Compared to patients with HCC, patients who underwent liver resection for HCA with malignant transformation had better long-term survival.
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Key Words
- H-HCA, HNF1α-mutated HCAs
- HCA, hepatocellular adenoma
- HCC, hepatocellular carcinoma
- Hepatocellular adenoma
- IHCA, inflammatory HCA
- LFABP, liver fatty acid binding protein
- LR, liver resection
- MT-HCA, malignant transformation HCA
- NP-HCC, HCC occurring on normal parenchyma
- RFS, recurrence-free survival
- SF-HCA, small foci of malignant transformation HCA
- U-HCA, unclassified HCA
- liver resection
- malignant transformation
- recurrence
- β-HCA, β-catenin-mutated HCA
- β-IHCA, β-catenin-mutated inflammatory HCA
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Affiliation(s)
- Sophie Chopinet
- Department of HPB and Liver Transplantation, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris and Université de Paris, Clichy, France
| | - François Cauchy
- Department of HPB and Liver Transplantation, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris and Université de Paris, Clichy, France
| | - Christian Hobeika
- Department of HPB and Liver Transplantation, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris and Université de Paris, Clichy, France
| | - Aurélie Beaufrère
- Department of Pathology, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris and Université de Paris, Clichy, France
| | - Nicolas Poté
- Department of Pathology, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris and Université de Paris, Clichy, France
| | - Olivier Farges
- Department of HPB and Liver Transplantation, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris and Université de Paris, Clichy, France
| | - Safi Dokmak
- Department of HPB and Liver Transplantation, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris and Université de Paris, Clichy, France
| | - Mohamed Bouattour
- Department of Oncology, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris and Université de Paris, Clichy, France
| | - Maxime Ronot
- Department of Radiology, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris and Université de Paris, Clichy, France
| | - Valérie Vilgrain
- Department of Radiology, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris and Université de Paris, Clichy, France
| | - Valérie Paradis
- Department of Pathology, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris and Université de Paris, Clichy, France
| | - Olivier Soubrane
- Department of HPB and Liver Transplantation, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris and Université de Paris, Clichy, France
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24
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Haring MPD, Cuperus FJC, Duiker EW, de Haas RJ, de Meijer VE. Scoping review of clinical practice guidelines on the management of benign liver tumours. BMJ Open Gastroenterol 2021; 8:e000592. [PMID: 34362758 PMCID: PMC8351490 DOI: 10.1136/bmjgast-2020-000592] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2020] [Accepted: 07/18/2021] [Indexed: 12/18/2022] Open
Abstract
OBJECTIVE Benign liver tumours (BLT) are increasingly diagnosed as incidentalomas. Clinical implications and management vary across and within the different types of BLT. High-quality clinical practice guidelines are needed, because of the many nuances in tumour types, diagnostic modalities, and conservative and invasive management strategies. Yet, available observational evidence is subject to interpretation which may lead to practice variation. Therefore, we aimed to systematically search for available clinical practice guidelines on BLT, to critically appraise them, and to compare management recommendations. DESIGN A scoping review was performed within MEDLINE, EMBASE, and Web of Science. All BLT guidelines published in peer-reviewed, and English language journals were eligible for inclusion. Clinical practice guidelines on BLT were analysed, compared, and critically appraised using the Appraisal of Guidelines, Research and Evaluation (AGREE II) checklist regarding hepatic haemangioma, focal nodular hyperplasia (FNH), and hepatocellular adenoma (HCA). Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations (PRISMA) for scoping reviews were adhered to. RESULTS The literature search yielded unique 367 papers, 348 were excluded after screening of title/abstract, and 16 after full-text screening. Three guidelines were included: the American College of Gastroenterology (ACG; 2014), Brazilian Society of Hepatology (SBH; 2015), and European Association for the Study of the Liver (EASL; 2016). There was no uniformity in the assessment methods for grading and gravity of recommendations between guidelines. Among observed differences were: (1) indications for biopsy in all three tumours; (2) advices on contraceptive pills and follow-up in FNH and HCA; (3) use of an individualised approach to HCA; (4) absence of recommendations for treatment of HCA in men; and (5) approaches to HCA subtype identification on magnetic resonance imaging. CONCLUSION Recognising differences in recommendations can assist in harmonisation of practice standards and identify unmet needs in research. This may ultimately contribute to improved global patient care.
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Affiliation(s)
- Martijn P D Haring
- Department of Surgery, University Medical Centre Groningen, Groningen, The Netherlands
| | - Frans J C Cuperus
- Department of Hepatology and Gastroenterology, University Medical Centre Groningen, Groningen, The Netherlands
| | - Evelien W Duiker
- Department of Medical Biology and Pathology, University Medical Centre Groningen, Groningen, The Netherlands
| | - Robbert J de Haas
- Department of Radiology, University Medical Centre Groningen, Groningen, The Netherlands
| | - Vincent E de Meijer
- Department of Surgery, University Medical Centre Groningen, Groningen, The Netherlands
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25
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Zhang H, Ding R, Chen D. Value of miR-21 levels as potential biomarkers in the early diagnosis of hepatocellular carcinoma：a meta-analysis. Biomarkers 2021; 26:586-597. [PMID: 34266326 DOI: 10.1080/1354750x.2021.1955976] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
BACKGROUND Many studies have reported that miR-21 levels are different between hepatocellular carcinoma (HCC) patients and healthy controls, which could be used as a potential diagnostic biomarker for HCC. However, the diagnostic value of miR-21 for HCC varied greatly in previous studies. Therefore, this meta-analysis aims to provide higher grade evidence to investigate the diagnostic value of miR-21 for HCC. METHODS The databases of PubMed, Embase, Web of Science, and Chinese databases (CNKI and VIP) were searched. The indices of miR-21 in the diagnosis of HCC were pooled using bivariate random-effect models. QUADAS-2 was used to evaluate the quality of included studies. All statistical analyses were performed by STATA (12.0) software. RESULTS Totally, 1589 subjects from 14 publications were included in this study. The pooled sensitivity, specificity, positive likelihood ratios (PLR), negative likelihood ratios (NLR), and area under the curve (AUC) were 0.83 (0.77-0.88), 0.80 (0.74-0.85), 4.12 (3.04-5.57), 0.21 (0.15-0.30), and 0.88 (0.85-0.91), respectively. Subgroup analysis showed that the AUC was higher in Non-China subgroup, qRT-PCR subgroup, and plasma subgroup than that in China subgroup, ddPCR subgroup, and serum subgroup, respectively. However, the AUC was not significantly different between the healthy control subgroup and chronic hepatitis control subgroup. Significant heterogeneity was found in this meta-analysis, while no evident publication bias was identified. CONCLUSIONS miR-21 is a valuable biomarker for the early diagnosis of HCC.
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Affiliation(s)
- Huiying Zhang
- School of Public Health, Anhui Medical University, Hefei, China
| | - Rui Ding
- School of Public Health, Anhui Medical University, Hefei, China
| | - Daojun Chen
- School of Public Health, Anhui Medical University, Hefei, China
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26
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Herman P, Fonseca GM, Kruger JAP, Jeismann VB, Coelho FF. Guidelines for the Treatment of Hepatocellular Adenoma in the Era of Molecular Biology: An Experience-Based Surgeons' Perspective. J Gastrointest Surg 2021; 25:1494-1502. [PMID: 32666496 DOI: 10.1007/s11605-020-04724-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Accepted: 06/28/2020] [Indexed: 01/31/2023]
Abstract
BACKGROUND Hepatocellular adenoma (HA) is a rare benign liver tumor with increasing incidence affecting young women. In the last years, much has changed in diagnosis, classification, and treatment, due to the identification of different molecular subtypes. With the evolving knowledge, especially on molecular characteristics of the disease, we are far from a consensus of how to deal with such a multifaceted benign disease METHODS: In the last 20 years, we have treated 134 patients with HA with a mean age of 28 years, being 126 women. Fifty patients had a history of abdominal pain and 13 patients had an acute episode of pain due to rupture and bleeding. Until 2009, adenomas larger than 4 cm in diameter were resected, regardless of gender. From 2010 to 2016, only adenomas larger than 5 cm were referred for surgical treatment. Since 2016, resection was indicated in all female patients with non-steatotic adenomas larger than 5 cm and all adenomas in men. RESULTS AND DISCUSSION One hundred twenty-four patients were submitted to resection, being in 21 major resections. Since 2010, 74% of resections were done laparoscopically. Patients with ruptured adenomas were treated with transarterial embolization. Morbidity rate was 8.1% with no mortality. Authors discuss point-by-point all the aspects and presentations of the disease and the best approach. We proposed a therapeutic guideline based on the best available evidence and in our experience. CONCLUSIONS Due to the complexity of the disease, the treatment of HA is one the best examples of an individualized approach.
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Affiliation(s)
- Paulo Herman
- Digestive Surgery Division, Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, Brazil.
| | - Gilton Marques Fonseca
- Digestive Surgery Division, Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, Brazil
| | - Jaime Arthur Pirola Kruger
- Digestive Surgery Division, Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, Brazil
| | - Vagner Birk Jeismann
- Digestive Surgery Division, Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, Brazil
| | - Fabricio Ferreira Coelho
- Digestive Surgery Division, Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, Brazil
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27
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Elbanna KY, Kielar AZ. Computed Tomography Versus Magnetic Resonance Imaging for Hepatic Lesion Characterization/Diagnosis. Clin Liver Dis (Hoboken) 2021; 17:159-164. [PMID: 33868658 PMCID: PMC8043714 DOI: 10.1002/cld.1089] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2020] [Revised: 12/07/2020] [Accepted: 01/03/2021] [Indexed: 02/04/2023] Open
Affiliation(s)
- Khaled Y. Elbanna
- Toronto Joint Department of Medical ImagingUniversity Health NetworkSinai Health System and Women’s College HospitalUniversity of TorontoTorontoONCanada
| | - Ania Z. Kielar
- Toronto Joint Department of Medical ImagingUniversity Health NetworkSinai Health System and Women’s College HospitalUniversity of TorontoTorontoONCanada,The University of OttawaOttawaCanada
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28
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Subramanian M, Low HM, Kim MJ, Tan CH. Benign focal liver lesions masquerading as primary liver cancers on MRI. ACTA ACUST UNITED AC 2021; 26:168-175. [PMID: 32229432 DOI: 10.5152/dir.2019.19235] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are the most common primary liver malignancies. HCC and ICC have characteristic imaging findings, but a number of benign entities can appear similar and can cause diagnostic dilemma. Ideally, accurate and timely diagnosis of these conditions can help the patient to avoid a needle biopsy or even unnecessary treatment. In this article, we present various benign liver lesions that display imaging characteristics that are similar to HCC and ICC on magnetic resonance imaging (MRI) and discuss salient features that may assist in accurate diagnosis.
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Affiliation(s)
| | - Hsien Min Low
- Department of Diagnostic Radiology, Tan Tock Seng Hospital, Novena, Singapore
| | - Myeong-Jin Kim
- Department of Diagnostic Radiology, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Cher Heng Tan
- Department of Diagnostic Radiology, Tan Tock Seng Hospital, Novena, Singapore
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29
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Vernuccio F, Austin S, Meyer M, Guy CD, Kishnani PS, Marin D. "Bull’s eye” appearance of hepatocellular adenomas in patients with glycogen storage disease type I — atypical magnetic resonance imaging findings: Two case reports. World J Clin Cases 2021; 9:871-877. [PMID: 33585634 PMCID: PMC7852632 DOI: 10.12998/wjcc.v9.i4.871] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2020] [Revised: 12/10/2020] [Accepted: 12/29/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hepatocellular adenomas are rare tumors that can occur in patients with glycogen storage disease type I.
CASE SUMMARY We herein report two cases of histologically proven hepatocellular adenomas in patients with glycogen storage disease type I. Magnetic resonance imaging (MRI) was performed after bolus injection of gadoxetate disodium, a liver-specific gadolinium-based MRI contrast agent. In the present cases, some of the hepatocellular adenomas showed unexpectedly a “bull’s eye” appearance on T2-weighted and post-contrast images, which was not previously described as imaging findings of hepatocellular adenomas in glycogen storage disease. A bull’s eye appearance on T2-weighted images can be encountered in both benign (i.e., abscess) or malignant (i.e., epithelioid hemangioendothelioma, cholangio-carcinoma, and metastases) hepatic lesions.
CONCLUSION We present two cases of hepatocellular adenomas in patients with glycogen storage disease type 1, in which gadoxetate disodium-MRI showed atypical imaging findings for hepatocellular adenomas. At present there is no systematic study evaluating MRI findings of hepatocellular adenomas in patients with glycogen storage disease, further studies are needed to specifically investigate this issue.
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Affiliation(s)
- Federica Vernuccio
- Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, Palermo 90100, Italy
| | - Stephanie Austin
- Departments of Pediatrics, Duke University Medical Center, Durham, NC 27710, United States
| | - Mathias Meyer
- Department of Radiology, Duke University Medical Hospital, Durham, NC 27708, United States
| | - Cynthia D Guy
- Department of Pathology, Duke University, Durham, NC 27710, United States
| | - Priya S Kishnani
- Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, United States
| | - Daniele Marin
- Department of Radiology, Duke University Medical Center, Durham, NC 27710, United States
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30
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Mittal S, Gopal P, Khatri G, Singal AG. Evaluation and Management of Hepatocellular Adenomas. Clin Liver Dis (Hoboken) 2021; 17:57-60. [PMID: 33680436 PMCID: PMC7916436 DOI: 10.1002/cld.949] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2019] [Revised: 12/29/2019] [Accepted: 02/05/2020] [Indexed: 02/04/2023] Open
Affiliation(s)
- Sukul Mittal
- Division of Digestive and Liver DiseasesUT Southwestern Medical CenterDallasTX
- Department of PathologyUT Southwestern Medical CenterDallasTX
- Department of RadiologyUT Southwestern Medical CenterDallasTX
| | - Purva Gopal
- Division of Digestive and Liver DiseasesUT Southwestern Medical CenterDallasTX
- Department of PathologyUT Southwestern Medical CenterDallasTX
- Department of RadiologyUT Southwestern Medical CenterDallasTX
| | - Gaurav Khatri
- Division of Digestive and Liver DiseasesUT Southwestern Medical CenterDallasTX
- Department of PathologyUT Southwestern Medical CenterDallasTX
- Department of RadiologyUT Southwestern Medical CenterDallasTX
| | - Amit G. Singal
- Division of Digestive and Liver DiseasesUT Southwestern Medical CenterDallasTX
- Department of PathologyUT Southwestern Medical CenterDallasTX
- Department of RadiologyUT Southwestern Medical CenterDallasTX
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31
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Moosavi B, Shenoy-Bhangle AS, Tsai LL, Reuf R, Mortele KJ. MRI characterization of focal liver lesions in non-cirrhotic patients: assessment of added value of gadoxetic acid-enhanced hepatobiliary phase imaging. Insights Imaging 2020; 11:101. [PMID: 32960337 PMCID: PMC7509030 DOI: 10.1186/s13244-020-00894-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Accepted: 07/16/2020] [Indexed: 12/15/2022] Open
Abstract
Background To evaluate the added value of the hepatobiliary (HPB) phase in gadoxetic acid-enhanced magnetic resonance imaging (MRI) in characterizing newly discovered indeterminate focal liver lesions in non-cirrhotic patients. Results One-hundred and twenty-five non-cirrhotic patients (median age, 46 years; range, 20–85 years; 100 females) underwent gadoxetic acid-enhanced MRI, including the 20-min delayed HPB phase, for characterization of newly discovered focal liver lesions. Images were independently evaluated by two blinded, board-certified abdominal radiologists (R1 and R2) who characterized liver lesions without and with assessment of the HPB phase images in two separate readout sessions. Confidence in diagnosis was scored on a scale from 0 to 3. Inter-observer agreement was assessed using Cohen κ statistics. Change in diagnosis and confidence in diagnosis were evaluated by Wilcoxon signed rank test. There was no significant change in diagnosis before and after evaluation of the HPB phase for both readers (p = 1.0 for R1; p = 0.34 for R2). Confidence in diagnosis decreased from average 2.8 ± 0.45 to 2.6 ± 0.59 for R1 and increased from 2.6 ± 0.83 to 2.8 ± 0.46 for R2. Change in confidence was only statistically significant for R1 (p = 0.003) but not significant for R2 (p = 0.49). Inter-reader agreement in diagnosis was good without (k = 0.66) and with (k = 0.75) inclusion of the HPB phase images. Conclusions The added information obtained from the HPB phase of gadoxetic acid-enhanced MRI does not change the diagnosis or increase confidence in diagnosis when evaluating new indeterminate focal liver lesions in non-cirrhotic patients.
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Affiliation(s)
- Bardia Moosavi
- Department of Radiology, Hull Hospital, Gatineau, Quebec, J8Y1W7, Canada.
| | - Anuradha S Shenoy-Bhangle
- Division of Abdominal Imaging, Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave, Boston, MA, 02215, USA
| | - Leo L Tsai
- Division of Abdominal Imaging, Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave, Boston, MA, 02215, USA
| | - Robert Reuf
- Department of Radiology, Hull Hospital, Gatineau, Quebec, J8Y1W7, Canada.,Division of Abdominal Imaging, Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave, Boston, MA, 02215, USA
| | - Koenraad J Mortele
- Department of Radiology, Hull Hospital, Gatineau, Quebec, J8Y1W7, Canada.,Division of Abdominal Imaging, Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave, Boston, MA, 02215, USA
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32
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Oldhafer KJ, Habbel V, Horling K, Makridis G, Wagner KC. Benign Liver Tumors. Visc Med 2020; 36:292-303. [PMID: 33005655 DOI: 10.1159/000509145] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2020] [Accepted: 06/03/2020] [Indexed: 12/12/2022] Open
Abstract
Background Due to the frequent use of medical imaging including ultrasonography, the incidence of benign liver tumors has increased. There is a large variety of different solid benign liver tumors, of which hemangioma, focal nodular hyperplasia (FNH), and hepatocellular adenoma (HCA) are the most frequent. Advanced imaging techniques allow precise diagnosis in most of the patients, which reduces the need for biopsies only to limited cases. Patients with benign liver tumors are mostly asymptomatic and do not need any kind of treatment. Symptoms can be abdominal pain and pressure effects on adjacent structures. The 2 most serious complications are bleeding and malignant transformation. Summary This review focuses on hepatic hemangioma (HH), FNH, and HCA, and provides an overview on clinical presentations, surgical and interventional treatment, as well as conservative management. Treatment options for HHs, if indicated, include liver resection, radiofrequency ablation, and transarterial catheter embolization, and should be carefully weighed against possible complications. FNH is the most frequent benign liver tumor without any risk of malignant transformation, and treatment should only be restricted to symptomatic patients. HCA is associated with the use of oral contraceptives or other steroid medications. Unlike other benign liver tumors, HCA may be complicated by malignant transformation. HCAs have been divided into 6 subtypes based on molecular and pathological features with different risk of complication. Key Message The vast majority of benign liver tumors remain asymptomatic, do not increase in size, and rarely need treatment. Biopsies are usually not needed as accurate diagnosis can be obtained using modern imaging techniques.
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Affiliation(s)
- Karl J Oldhafer
- Department für Chirurgie, Klinik für Leber-, Gallenwegs- und Pankreaschirurgie, Asklepios Klinik Barmbek, Hamburg, Germany.,Semmelweis University Budapest, Asklepios Campus Hamburg, Hamburg, Germany
| | - Victoria Habbel
- Department für Chirurgie, Klinik für Leber-, Gallenwegs- und Pankreaschirurgie, Asklepios Klinik Barmbek, Hamburg, Germany.,Semmelweis University Budapest, Asklepios Campus Hamburg, Hamburg, Germany
| | | | - Georgios Makridis
- Department für Chirurgie, Klinik für Leber-, Gallenwegs- und Pankreaschirurgie, Asklepios Klinik Barmbek, Hamburg, Germany.,Semmelweis University Budapest, Asklepios Campus Hamburg, Hamburg, Germany
| | - Kim Caroline Wagner
- Department für Chirurgie, Klinik für Leber-, Gallenwegs- und Pankreaschirurgie, Asklepios Klinik Barmbek, Hamburg, Germany.,Semmelweis University Budapest, Asklepios Campus Hamburg, Hamburg, Germany
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Abstract
Focal nodular hyperplasia and hepatocellular adenoma are benign liver lesions that occur most frequently in women and may be found as incidental findings on imaging. hepatocellular adenomas may be infrequently associated with malignant progression or risk of rupture and as such, require surveillance or definitive treatments based on their size threshold. It is important clinically to differentiate these lesions, and utilizing imaging modalities such as contrast enhanced ultrasound or magnetic resonance imaging can be helpful in diagnosis. Further molecular subtyping of hepatocellular adenoma lesions may be beneficial to describe risk factors and potential future clinical complications.
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Affiliation(s)
- Lauren Myers
- Division of Gastroenterology and Hepatology, Oregon Health and Science University, 3181 Southwest Sam Jackson Park Road, MNP 4112, Portland, OR 97239, USA.
| | - Joseph Ahn
- Division of Gastroenterology and Hepatology, Oregon Health and Science University, 3181 Southwest Sam Jackson Park Road, MNP 4112, Portland, OR 97239, USA
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Rodrigues BT, Mei SLCY, Fox A, Lubel JS, Nicoll AJ. A systematic review on the complications and management of hepatic adenomas: a call for a new approach. Eur J Gastroenterol Hepatol 2020; 32:923-930. [PMID: 32433418 DOI: 10.1097/meg.0000000000001766] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
Hepatic adenomas are benign hepatic lesions with heterogeneous characteristics. Awareness of complications, including haemorrhage and malignant transformation, has improved alongside a concurrent rise in their detection. Monitoring and management guidelines, however, remain inconsistent. This systematic review analyses the natural history of hepatic adenomas, and existing and novel risk factors associated with haemorrhage and malignant transformation. Results of this systematic review commonly identified male sex, and the beta-catenin histopathological hepatic adenoma subtype, as risk factors for malignant transformation, whilst those associated with haemorrhage included lesion size and number, exophytic nature, and recent hormone use. Overall, females demonstrated higher rates of haemorrhage, whilst males exhibited a higher risk of hepatocellular carcinoma development. This systematic review highlights that tumour size and subtype may not be as characteristically linked with complications as previously thought. We have additionally reported novel risk factors contributing to development of hepatic adenoma-related complications. We conclude by highlighting the risk of taking a conservative approach to seemingly low-risk lesions and suggest revised practice guidelines.
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Affiliation(s)
- Beverly T Rodrigues
- Department of Gastroenterology, Eastern Health.,School of Medicine, Monash University, Eastern Health Clinical School, Monash University
| | | | - Adrian Fox
- Department of Gastroenterology, Eastern Health
| | - John S Lubel
- Department of Gastroenterology, Alfred Health, Melbourne, Victoria 3128, Australia
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35
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Wang L, Wang C, Li W, Meng F, Li Y, Fan H, Zhou Y, Bharathi G, Gao S, Yang Y. Multiple hepatocellular adenomas associated with long-term administration of androgenic steroids for aplastic anemia: A case report and literature review. Medicine (Baltimore) 2020; 99:e20829. [PMID: 32664077 PMCID: PMC7360229 DOI: 10.1097/md.0000000000020829] [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: 12/26/2022] Open
Abstract
INTRODUCTION Anabolic steroids are widely administered to patients with aplastic anemia (AA) and are associated with numerous medical complications. To assist with future diagnoses, we report about a young boy with multiple hepatocellular adenomas (HAs) induced by long-term use of anabolic androgenic steroids (AAS) for AA and present a related literature review. PATIENT CONCERN A 15-year-old boy who was diagnosed with AA in 2011 had been treated with stanozolol (6 mg per day) and ciclosporin A (120-150 mg per day) for almost 4 years. He presented with epigastric pain and fever, and abdominal computed tomography showed a lesion of heterogenous density measuring 13.5 × 13.0 × 8.0 cm in the left hepatic lobe, which was initially misdiagnosed as a liver abscess. DIAGNOSIS The patient went into hemorrhagic shock twice after invasive manipulation that aimed at diagnosis and was finally diagnosed with HA using fine needle aspiration. INTERVENTIONS The patient discontinued AAS and only reserved ciclosporin A for AA treatment. OUTCOMES Follow-up abdominal computed tomography performed 4 years after AAS discontinuation showed obvious regression of the hepatic lesions. CONCLUSION It is of great importance for hematologists to completely understand that the long-term use of AAS may cause HA, which carries a great risk of hemorrhage and malignant transformation.
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Affiliation(s)
| | - Cong Wang
- Department of Radiology, The First Hospital of Jilin University
| | | | - Fanyang Meng
- Department of Radiology, The First Hospital of Jilin University
| | | | | | - Yanhua Zhou
- Department of Hematology, the Qianwei Hospital of Jilin Province, Changchun, Jilin, China
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36
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Klompenhouwer AJ, de Man RA, Dioguardi Burgio M, Vilgrain V, Zucman‐Rossi J, Ijzermans JNM. New insights in the management of Hepatocellular Adenoma. Liver Int 2020; 40:1529-1537. [PMID: 32464711 PMCID: PMC7383747 DOI: 10.1111/liv.14547] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2020] [Revised: 04/30/2020] [Accepted: 05/21/2020] [Indexed: 12/12/2022]
Abstract
Hepatocellular adenoma (HCA) are benign liver tumours that may be complicated by haemorrhage or malignant transformation to hepatocellular carcinoma. Epidemiological data are fairly outdated, but it is likely to assume that the incidence has increased over the past decades as HCA are more often incidentally found due to the more widespread use of imaging techniques and the increased incidence of obesity. Various molecular subgroups have been described. Each of these molecular subgroups are defined by specific gene mutations and pathway activations. Additionally, they are all related to specific risk factors and show a various biological behaviour. These molecular subgroups may be identified using immunohistochemistry and molecular characterization. Contrast-enhanced MRI is the recommended imaging modality to analyse patients with suspected hepatocellular adenoma allowing to determine the subtype in up to 80%. Surgical resection remains to be the golden standard in treating HCA, although resection is deemed unnecessary in a large number of cases, as studies have shown that the majority of HCA will regress over time without complications such as haemorrhage or malignant transformation occurring. It is preferable to treat patients with suspected HCA in high volume centres with combined expertise of liver surgeons, hepatologists, radiologists and (molecular) pathologists.
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Affiliation(s)
| | - Robert A. de Man
- Department of Gastroenterology and HepatologyErasmus MC University Medical CenterRotterdamthe Netherlands
| | - Marco Dioguardi Burgio
- Department of RadiologyHauts‐de‐SeineUniversity Hospitals Paris Nord Val de SeineBeaujon, APHPClichyFrance,Centre de Recherche sur l'inflammation (CRI)INSERM U1149et Université de ParisParisFrance
| | - Valerie Vilgrain
- Department of RadiologyHauts‐de‐SeineUniversity Hospitals Paris Nord Val de SeineBeaujon, APHPClichyFrance,Centre de Recherche sur l'inflammation (CRI)INSERM U1149et Université de ParisParisFrance
| | - Jessica Zucman‐Rossi
- Centre de Recherche des CordeliersSorbonne Université, INSERMUniversité de ParisParisFrance,Oncology DepartmentAPHPHôpital européen Georges PompidouParisFrance
| | - Jan N. M. Ijzermans
- Department of SurgeryErasmus MC University Medical CenterRotterdamthe Netherlands
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37
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Krause K, Tanabe KK. ASO Author Reflections: Developing Personalized Care for Hepatocellular Adenoma Based on Subtype Classification. Ann Surg Oncol 2020; 27:3339-3340. [PMID: 32548754 DOI: 10.1245/s10434-020-08681-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2020] [Indexed: 11/18/2022]
Affiliation(s)
- Kate Krause
- Division of Surgical Oncology, Massachusetts General Hospital, Boston, MA, USA
| | - Kenneth K Tanabe
- Division of Surgical Oncology, Massachusetts General Hospital, Boston, MA, USA.
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Krause K, Tanabe KK. A Shifting Paradigm in Diagnosis and Management of Hepatic Adenoma. Ann Surg Oncol 2020; 27:3330-3338. [PMID: 32542565 DOI: 10.1245/s10434-020-08580-w] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2020] [Indexed: 12/14/2022]
Abstract
BACKGROUND New insights into molecular pathogenesis of hepatocellular adenomas (HCA) have allowed sub-classification based on distinct genetic alterations and a fresh look at characterizations of natural history. Clinically, this is important in understanding risk factors for two feared complications: malignant transformation and hemorrhage. METHODS PubMed literature search for hepatocellular adenoma over all years, excluding case reports and articles focusing on multiple adenomas or adenomatosis. RESULTS The β-catenin exon 3 mutated HCA accounts for about 10% of all HCAs and is associated with the highest risk of malignant transformation. The HF1α subtype accounts for 30-40% of all HCAs and has the lowest risk of malignant transformation. Gender has also emerged as an increasingly important risk factor and males with HCA are at considerably higher risk of malignant transformation, regardless of tumor size. The increasing use of gadoxetic-enhanced MRI has allowed for improved differentiation of HCAs from focal nodular hyperplasia, as well as the identification of specific radiologic features of some subtypes, particularly the inflammatory and HF1α HCAs. CONCLUSIONS Classification of HCA by subtype has important implications for patient counseling and treatment given variable risks of malignant transformation and hemorrhage. Males and those with β-catenin exon 3 mutated HCAs are two groups who should always be counselled to undergo surgical resection. On the other hand, in the lower risk HF1α subtype observation is appropriate in lesions < 5 cm and may even be considered in larger lesions as longer follow-up data is aggregated and tumorigenesis is better understood.
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Affiliation(s)
- Kate Krause
- Division of Surgical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Kenneth K Tanabe
- Division of Surgical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
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39
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Gregory J, Paisant A, Paulatto L, Raynaud L, Bertin C, Kerbaol A, Vullierme MP, Paradis V, Vilgrain V, Ronot M. Limited added value of contrast-enhanced ultrasound over B-mode for the subtyping of hepatocellular adenomas. Eur J Radiol 2020; 128:109027. [PMID: 32361381 DOI: 10.1016/j.ejrad.2020.109027] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2019] [Revised: 03/30/2020] [Accepted: 04/15/2020] [Indexed: 12/21/2022]
Abstract
PURPOSE To compare the features of hepatocellular adenoma subtypes (HCAs) in B-mode and contrast-enhanced ultrasound (CEUS). METHOD Thirty-three patients (31 women [94 %] and two men [6%], median age [Q1-Q3] 43.5 years old [35-51]) with 44 pathologically proven and subtyped HCAs (including 29 inflammatory HCAs [I-HCA] and 15 HNF1-α inactivated HCAs [H-HCA]) who underwent CEUS were included. The features of HCA on B-mode and CEUS were independently reviewed by two radiologists and compared between HCA subtypes. RESULTS I-HCAs were mostly hypoechoic (23/29, 79 %) or isoechoic (4/29, 14 %) with B-mode. Twelve of them (41 %) were heterogeneous. All H-HCAs except one demonstrated homogeneous hyperechogenicity (93 %) (p = 0.001). Moderate or marked liver steatosis was only observed in I-HCAs (12/29, 41 %) (p = 0.001). Arterial hyperenhancement was observed on CEUS in 27/29 (93 %) I-HCAs and in 14/15 (93 %) H-HCAs (p=0.98). Washout was present in 6/29 (21 %) I-HCAs and 1/15 (7%) H-HCAs (p=0.27). A total of 23/29 (79 %) I-HCAs and 15/15 (100 %) HCAs were homogeneous on portal and delayed phase acquisitions (p=0.04). The specificity for identifying an H-HCA was 100 % when the lesion was homogeneous and hyperechoic on B-mode, and the sensibility to rule out an H-HCA was 100 % if neither of these two features was present in a liver with obvious steatosis. CONCLUSIONS Most CEUS features, especially enhancement patterns, do not significantly differ between HCA subtypes. When HCA is suspected on CEUS, B-mode features should be considered, and a combination of lesion hyperechogenicity, homogeneity and the absence of obvious liver steatosis may be useful to distinguish H-HCAs from I-HCAs.
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Affiliation(s)
- Jules Gregory
- Assistance Publique - Hôpitaux de Paris, Hôpitaux Universitaires Paris Nord Val de Seine, Hôpital Beaujon, Clichy, France; Université de Paris, Faculté de Médecine, Paris, France
| | - Anita Paisant
- Assistance Publique - Hôpitaux de Paris, Hôpitaux Universitaires Paris Nord Val de Seine, Hôpital Beaujon, Clichy, France
| | - Luisa Paulatto
- Assistance Publique - Hôpitaux de Paris, Hôpitaux Universitaires Paris Nord Val de Seine, Hôpital Beaujon, Clichy, France
| | - Lucas Raynaud
- Assistance Publique - Hôpitaux de Paris, Hôpitaux Universitaires Paris Nord Val de Seine, Hôpital Beaujon, Clichy, France
| | - Caroline Bertin
- Assistance Publique - Hôpitaux de Paris, Hôpitaux Universitaires Paris Nord Val de Seine, Hôpital Beaujon, Clichy, France
| | - Anne Kerbaol
- Assistance Publique - Hôpitaux de Paris, Hôpitaux Universitaires Paris Nord Val de Seine, Hôpital Beaujon, Clichy, France
| | - Marie-Pierre Vullierme
- Assistance Publique - Hôpitaux de Paris, Hôpitaux Universitaires Paris Nord Val de Seine, Hôpital Beaujon, Clichy, France; Université de Paris, Faculté de Médecine, Paris, France
| | - Valérie Paradis
- Assistance Publique - Hôpitaux de Paris, Hôpitaux Universitaires Paris Nord Val de Seine, Hôpital Beaujon, Clichy, France; Université de Paris, Faculté de Médecine, Paris, France; INSERM U1149, Centre de Recherche de l'Inflammation (CRI), Paris, France
| | - Valérie Vilgrain
- Assistance Publique - Hôpitaux de Paris, Hôpitaux Universitaires Paris Nord Val de Seine, Hôpital Beaujon, Clichy, France; Université de Paris, Faculté de Médecine, Paris, France; INSERM U1149, Centre de Recherche de l'Inflammation (CRI), Paris, France
| | - Maxime Ronot
- Assistance Publique - Hôpitaux de Paris, Hôpitaux Universitaires Paris Nord Val de Seine, Hôpital Beaujon, Clichy, France; Université de Paris, Faculté de Médecine, Paris, France; INSERM U1149, Centre de Recherche de l'Inflammation (CRI), Paris, France.
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40
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Vernuccio F, Ronot M, Dioguardi Burgio M, Cauchy F, Choudhury KR, Dokmak S, Soubrane O, Valla D, Zucman-Rossi J, Paradis V, Vilgrain V. Long-term Evolution of Hepatocellular Adenomas at MRI Follow-up. Radiology 2020; 295:361-372. [PMID: 32181728 DOI: 10.1148/radiol.2020191790] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Background Hepatocellular adenomas (HCAs) are rare benign liver tumors. Guidelines recommend continued surveillance of patients diagnosed with HCAs, but these guidelines are mainly based on small studies or expert opinion. Purpose To analyze the long-term evolution of HCAs, including solitary and multiple lesions, and to identify predictive features of progression with MRI. Materials and Methods In a retrospective study, patients diagnosed with pathologically proven solitary or multiple HCAs between January 2004 and December 2015 were included; β-catenin-mutated HCAs and HCAs with foci of malignancy were considered to be at risk for progression. MRI examinations were analyzed, and tumor evolution was evaluated by using Response Evaluation Criteria in Solid Tumors, version 1.1. Student t, Mann-Whitney, χ2, Fisher exact, and McNemar tests were used, as appropriate. Results In total, 118 patients (mean age, 40 years ± 10 [standard deviation]; 108 women) were evaluated, including 41 with a solitary HCA (mean age, 40 years ± 14; 36 women) and 77 with multiple HCAs (mean age, 40 years ± 10; 72 women). At a median follow-up of 5 years, 37 of 41 (90%) patients with a solitary HCA and 55 of 77 (71%) patients with multiple HCAs showed stable or regressive disease. After resection of solitary HCAs, new lesions appeared in only two of 29 (7%) patients, both of whom had HCAs at risk of progression. In patients with multiple HCAs, hepatocyte nuclear factor 1α-inactivated HCAs showed a higher rate of progression compared with inflammatory HCAs (11 of 26 [42%] vs seven of 37 [19%], P = .04) despite lower use (28 of 32 patients [88%] vs 45 of 45 patients [100%]; P = .03) and shorter duration (mean, 12.0 years ± 7.5 vs 19.2 years ± 9.2; P = .001) of oral contraceptive intake. Conclusion Long-term MRI follow-up showed that 78% of hepatocellular adenomas had long-term stability or regression. After resection of solitary hepatocellular adenomas, new lesions occurred only in hepatocellular adenomas at risk of progression. Patients with multiple hepatocellular adenomas were more likely to show progressive disease, with hepatic nuclear factor 1α-inactivated hepatocellular adenomas being the most common subtype showing progression. © RSNA, 2020 Online supplemental material is available for this article.
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Affiliation(s)
- Federica Vernuccio
- From the University of Paris, Paris, France (F.V., M.R., F.C., O.S., D.V., V.P., V.V.); Departments of Radiology (M.R., M.D.B., V.V.), Liver Transplantation and Hepatobiliary Surgery (F.C., S.D., O.S.), and Hepatology (D.V.), and Pathology Department (V.P.), University Hospitals Paris Nord Val de Seine, Beaujon, Clichy, Hauts-de-Seine, France; INSERM, UMR 1149, Paris, France (M.R., F.C., O.S., D.V., M.D.B., V.P., V.V.); Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC (K.R.C.); INSERM, UMR 1162, Génomique Fonctionnelle des Tumeurs Solides, Université Paris Descartes, Université Paris Diderot, Université Paris 13, Labex Immuno-Oncology, Paris, France (J.Z.), Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy (F.V.)
| | - Maxime Ronot
- From the University of Paris, Paris, France (F.V., M.R., F.C., O.S., D.V., V.P., V.V.); Departments of Radiology (M.R., M.D.B., V.V.), Liver Transplantation and Hepatobiliary Surgery (F.C., S.D., O.S.), and Hepatology (D.V.), and Pathology Department (V.P.), University Hospitals Paris Nord Val de Seine, Beaujon, Clichy, Hauts-de-Seine, France; INSERM, UMR 1149, Paris, France (M.R., F.C., O.S., D.V., M.D.B., V.P., V.V.); Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC (K.R.C.); INSERM, UMR 1162, Génomique Fonctionnelle des Tumeurs Solides, Université Paris Descartes, Université Paris Diderot, Université Paris 13, Labex Immuno-Oncology, Paris, France (J.Z.), Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy (F.V.)
| | - Marco Dioguardi Burgio
- From the University of Paris, Paris, France (F.V., M.R., F.C., O.S., D.V., V.P., V.V.); Departments of Radiology (M.R., M.D.B., V.V.), Liver Transplantation and Hepatobiliary Surgery (F.C., S.D., O.S.), and Hepatology (D.V.), and Pathology Department (V.P.), University Hospitals Paris Nord Val de Seine, Beaujon, Clichy, Hauts-de-Seine, France; INSERM, UMR 1149, Paris, France (M.R., F.C., O.S., D.V., M.D.B., V.P., V.V.); Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC (K.R.C.); INSERM, UMR 1162, Génomique Fonctionnelle des Tumeurs Solides, Université Paris Descartes, Université Paris Diderot, Université Paris 13, Labex Immuno-Oncology, Paris, France (J.Z.), Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy (F.V.)
| | - François Cauchy
- From the University of Paris, Paris, France (F.V., M.R., F.C., O.S., D.V., V.P., V.V.); Departments of Radiology (M.R., M.D.B., V.V.), Liver Transplantation and Hepatobiliary Surgery (F.C., S.D., O.S.), and Hepatology (D.V.), and Pathology Department (V.P.), University Hospitals Paris Nord Val de Seine, Beaujon, Clichy, Hauts-de-Seine, France; INSERM, UMR 1149, Paris, France (M.R., F.C., O.S., D.V., M.D.B., V.P., V.V.); Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC (K.R.C.); INSERM, UMR 1162, Génomique Fonctionnelle des Tumeurs Solides, Université Paris Descartes, Université Paris Diderot, Université Paris 13, Labex Immuno-Oncology, Paris, France (J.Z.), Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy (F.V.)
| | - Kingshuk R Choudhury
- From the University of Paris, Paris, France (F.V., M.R., F.C., O.S., D.V., V.P., V.V.); Departments of Radiology (M.R., M.D.B., V.V.), Liver Transplantation and Hepatobiliary Surgery (F.C., S.D., O.S.), and Hepatology (D.V.), and Pathology Department (V.P.), University Hospitals Paris Nord Val de Seine, Beaujon, Clichy, Hauts-de-Seine, France; INSERM, UMR 1149, Paris, France (M.R., F.C., O.S., D.V., M.D.B., V.P., V.V.); Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC (K.R.C.); INSERM, UMR 1162, Génomique Fonctionnelle des Tumeurs Solides, Université Paris Descartes, Université Paris Diderot, Université Paris 13, Labex Immuno-Oncology, Paris, France (J.Z.), Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy (F.V.)
| | - Safi Dokmak
- From the University of Paris, Paris, France (F.V., M.R., F.C., O.S., D.V., V.P., V.V.); Departments of Radiology (M.R., M.D.B., V.V.), Liver Transplantation and Hepatobiliary Surgery (F.C., S.D., O.S.), and Hepatology (D.V.), and Pathology Department (V.P.), University Hospitals Paris Nord Val de Seine, Beaujon, Clichy, Hauts-de-Seine, France; INSERM, UMR 1149, Paris, France (M.R., F.C., O.S., D.V., M.D.B., V.P., V.V.); Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC (K.R.C.); INSERM, UMR 1162, Génomique Fonctionnelle des Tumeurs Solides, Université Paris Descartes, Université Paris Diderot, Université Paris 13, Labex Immuno-Oncology, Paris, France (J.Z.), Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy (F.V.)
| | - Olivier Soubrane
- From the University of Paris, Paris, France (F.V., M.R., F.C., O.S., D.V., V.P., V.V.); Departments of Radiology (M.R., M.D.B., V.V.), Liver Transplantation and Hepatobiliary Surgery (F.C., S.D., O.S.), and Hepatology (D.V.), and Pathology Department (V.P.), University Hospitals Paris Nord Val de Seine, Beaujon, Clichy, Hauts-de-Seine, France; INSERM, UMR 1149, Paris, France (M.R., F.C., O.S., D.V., M.D.B., V.P., V.V.); Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC (K.R.C.); INSERM, UMR 1162, Génomique Fonctionnelle des Tumeurs Solides, Université Paris Descartes, Université Paris Diderot, Université Paris 13, Labex Immuno-Oncology, Paris, France (J.Z.), Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy (F.V.)
| | - Dominique Valla
- From the University of Paris, Paris, France (F.V., M.R., F.C., O.S., D.V., V.P., V.V.); Departments of Radiology (M.R., M.D.B., V.V.), Liver Transplantation and Hepatobiliary Surgery (F.C., S.D., O.S.), and Hepatology (D.V.), and Pathology Department (V.P.), University Hospitals Paris Nord Val de Seine, Beaujon, Clichy, Hauts-de-Seine, France; INSERM, UMR 1149, Paris, France (M.R., F.C., O.S., D.V., M.D.B., V.P., V.V.); Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC (K.R.C.); INSERM, UMR 1162, Génomique Fonctionnelle des Tumeurs Solides, Université Paris Descartes, Université Paris Diderot, Université Paris 13, Labex Immuno-Oncology, Paris, France (J.Z.), Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy (F.V.)
| | - Jessica Zucman-Rossi
- From the University of Paris, Paris, France (F.V., M.R., F.C., O.S., D.V., V.P., V.V.); Departments of Radiology (M.R., M.D.B., V.V.), Liver Transplantation and Hepatobiliary Surgery (F.C., S.D., O.S.), and Hepatology (D.V.), and Pathology Department (V.P.), University Hospitals Paris Nord Val de Seine, Beaujon, Clichy, Hauts-de-Seine, France; INSERM, UMR 1149, Paris, France (M.R., F.C., O.S., D.V., M.D.B., V.P., V.V.); Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC (K.R.C.); INSERM, UMR 1162, Génomique Fonctionnelle des Tumeurs Solides, Université Paris Descartes, Université Paris Diderot, Université Paris 13, Labex Immuno-Oncology, Paris, France (J.Z.), Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy (F.V.)
| | - Valérie Paradis
- From the University of Paris, Paris, France (F.V., M.R., F.C., O.S., D.V., V.P., V.V.); Departments of Radiology (M.R., M.D.B., V.V.), Liver Transplantation and Hepatobiliary Surgery (F.C., S.D., O.S.), and Hepatology (D.V.), and Pathology Department (V.P.), University Hospitals Paris Nord Val de Seine, Beaujon, Clichy, Hauts-de-Seine, France; INSERM, UMR 1149, Paris, France (M.R., F.C., O.S., D.V., M.D.B., V.P., V.V.); Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC (K.R.C.); INSERM, UMR 1162, Génomique Fonctionnelle des Tumeurs Solides, Université Paris Descartes, Université Paris Diderot, Université Paris 13, Labex Immuno-Oncology, Paris, France (J.Z.), Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy (F.V.)
| | - Valérie Vilgrain
- From the University of Paris, Paris, France (F.V., M.R., F.C., O.S., D.V., V.P., V.V.); Departments of Radiology (M.R., M.D.B., V.V.), Liver Transplantation and Hepatobiliary Surgery (F.C., S.D., O.S.), and Hepatology (D.V.), and Pathology Department (V.P.), University Hospitals Paris Nord Val de Seine, Beaujon, Clichy, Hauts-de-Seine, France; INSERM, UMR 1149, Paris, France (M.R., F.C., O.S., D.V., M.D.B., V.P., V.V.); Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC (K.R.C.); INSERM, UMR 1162, Génomique Fonctionnelle des Tumeurs Solides, Université Paris Descartes, Université Paris Diderot, Université Paris 13, Labex Immuno-Oncology, Paris, France (J.Z.), Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy (F.V.)
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Reizine E, Luciani A. Reply to "Intrapatient Comparison of the Hepatobiliary Phase of Gd-BOPTA and Gd-EOB-DTPA in the Differentiation of Hepatocellular Adenoma From Focal Nodular Hyperplasia". J Magn Reson Imaging 2020; 52:1279-1280. [PMID: 32022384 DOI: 10.1002/jmri.27074] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2020] [Revised: 01/11/2020] [Accepted: 01/13/2020] [Indexed: 11/05/2022] Open
Abstract
LEVEL OF EVIDENCE 5 TECHNICAL EFFICACY STAGE: 3 CONFLICT OF INTEREST: None. FINANCIAL SUPPORT None. J. Magn. Reson. Imaging 2020;52:1279-1280.
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Affiliation(s)
- Edouard Reizine
- Department of Radiology, APHP, HU Henri Mondor, Creteil, France
| | - Alain Luciani
- Department of Radiology, APHP, HU Henri Mondor, Creteil, France.,Faculté de Médecine, Universite Paris Est Creteil, Creteil, France.,INSERM Unit U 955, Creteil, France
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Vilgrain V, Raynaud L, Paulatto L, Ronot M. Imaging of liver tumours: What's new? Liver Int 2020; 40 Suppl 1:154-159. [PMID: 32077596 DOI: 10.1111/liv.14353] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2019] [Accepted: 12/26/2019] [Indexed: 02/13/2023]
Abstract
Liver tumours are very common and malignant tumours represent a major cause of cancer-related death. Imaging plays an important role at many different stages of the care pathway. This review discusses new aspects and new roles for imaging and for MRI, in particular. MRI is already the best tool for the characterization and staging of benign and malignant liver tumours and it could also become a useful screening tool, especially for hepatocellular carcinoma. Liver imaging will be increasingly quantitative in the future, integrating new approaches such as those of artificial intelligence.
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Affiliation(s)
- Valérie Vilgrain
- Department of Radiology, APHP, University Hospitals Paris Nord Val de Seine, Beaujon, Clichy, France.,University of Paris, CRI INSERM, Paris, France
| | - Lucas Raynaud
- Department of Radiology, APHP, University Hospitals Paris Nord Val de Seine, Beaujon, Clichy, France
| | - Luisa Paulatto
- Department of Radiology, APHP, University Hospitals Paris Nord Val de Seine, Beaujon, Clichy, France
| | - Maxime Ronot
- Department of Radiology, APHP, University Hospitals Paris Nord Val de Seine, Beaujon, Clichy, France.,University of Paris, CRI INSERM, Paris, France
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Growth of hepatocellular adenoma during pregnancy: A prospective study. J Hepatol 2020; 72:119-124. [PMID: 31550458 DOI: 10.1016/j.jhep.2019.09.011] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2019] [Revised: 08/28/2019] [Accepted: 09/10/2019] [Indexed: 12/29/2022]
Abstract
BACKGROUND & AIMS The presence of hepatocellular adenoma (HCA) in pregnant women requires special consideration, as it has been reported to carry the risk of growth and clinically significant haemorrhage. In this prospective study we assessed aspects of growth of HCA <5 cm during pregnancy. METHODS This was a multicentre prospective cohort study in pregnant women with suspected HCA <5 cm on imaging. Definitive HCA diagnosis was established by MRI with hepatobiliary contrast agents (LCE-MRI), preferably before pregnancy. If at study inclusion a definitive diagnosis was lacking, LCE-MRI was performed after giving birth. Growth of the adenoma (defined as an increase of >20%) was closely monitored with ultrasound examinations throughout pregnancy. RESULTS Of the 66 women included, 18 were excluded from analysis because postpartum LCE-MRI did not confirm the diagnosis of HCA and showed the lesion to be focal nodular hyperplasia. The remaining 48 women, with an HCA confirmed by LCE-MRI, were followed during 51 pregnancies. Median age was 30 years (IQR 27-33) and median body mass index 31.9 kg/m2 (IQR 26.3-36.6). Growth of HCA was seen in 13 of the pregnancies (25.5%); the median increase was 14 mm (IQR 8-19). One woman whose HCA grew to >70 mm successfully underwent transarterial embolization at week 26 of pregnancy to prevent further growth. The other 50 pregnancies proceeded without complications. CONCLUSION This study suggests that an HCA <5 cm confers minimal risk to a pregnant woman and none to her child. HCA increased in size during a quarter of pregnancies, so we recommend close monitoring with ultrasound examinations, enabling intervention if needed. In light of the large proportion of misdiagnosed HCA, LCE-MRI should be performed to prevent unnecessary anxiety in women with a benign liver lesion. LAY SUMMARY The presence of hepatocellular adenoma in pregnant women requires special consideration, as it carries the risk of growth and haemorrhage. In this study we followed 48 patients with hepatocellular adenoma <5 cm during 51 pregnancies and found that a hepatocellular adenoma during pregnancy confers minimal risk to the pregnant woman and none to her child.
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Jiang Y, He J, Li Y, Guo Y, Tao H. The Diagnostic Value of MicroRNAs as a Biomarker for Hepatocellular Carcinoma: A Meta-Analysis. BIOMED RESEARCH INTERNATIONAL 2019; 2019:5179048. [PMID: 31871941 PMCID: PMC6907051 DOI: 10.1155/2019/5179048] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/10/2019] [Revised: 10/15/2019] [Accepted: 11/05/2019] [Indexed: 12/24/2022]
Abstract
BACKGROUND Recently, the role of microRNAs (miRNAs) in diagnosing cancer has been attracted increasing attention. However, few miRNAs have been applied in clinical practice. The purpose of this study was to evaluate the diagnostic efficacy of miRNAs for hepatocellular carcinoma (HCC) at early stages clinically. METHODS A literature search was carried out using PubMed, Web of Science, and EMBASE databases. We explored the diagnostic value of miRNAs in distinguishing HCC from healthy individuals. The quality assessment was performed in Review Manager 5.3 software. The overall sensitivity and specificity and 95% confidence intervals (CIs) were obtained with random-effects models through Stata 14.0 software. And heterogeneity was assessed using Q test and I 2 statistics. Meta-regression and subgroup analyses were conducted based on the sample, nation, quality of studies, and miRNA profiling. The publication bias was evaluated through Deeks' funnel plot. RESULTS A total of 34 studies, involving in 2747 HCC patients and 2053 healthy individuals, met the inclusion criteria in the 33 included literature studies. In the summary receiver operating characteristic (sROC) curve, AUC was 0.92 (95% CI, 0.90-0.94), with 0.84 (95% CI, 0.79-0.88) sensitivity and 0.87 (95% CI, 0.83-0.90) specificity. There was no publication bias (P=0.48). CONCLUSION miRNAs in vivo can be acted as a potential diagnostic biomarker for HCC, which can facilitate the early diagnosis of HCC in clinical practice.
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Affiliation(s)
- Yao Jiang
- Department of Clinical Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Jimin He
- Department of Neurosurgery, Suining Central Hospital, Suining, China
| | - Yiqin Li
- Department of Clinical Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Yongcan Guo
- Clinical Laboratory of Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, China
| | - Hualin Tao
- Department of Clinical Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, China
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Tran Cao HS, Marcal LP, Mason MC, Yedururi S, Joechle K, Wei SH, Vauthey JN. Benign hepatic incidentalomas. Curr Probl Surg 2019; 56:100642. [DOI: 10.1067/j.cpsurg.2019.05.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2019] [Accepted: 05/09/2019] [Indexed: 12/13/2022]
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Zulfiqar M, Sirlin CB, Yoneda N, Ronot M, Hecht EM, Chernyak V, Matsui O, Bastati N, Ba‐Ssalamah A, Chatterjee D, Bashir M, Fowler KJ. Hepatocellular adenomas: Understanding the pathomolecular lexicon, MRI features, terminology, and pitfalls to inform a standardized approach. J Magn Reson Imaging 2019; 51:1630-1640. [DOI: 10.1002/jmri.26902] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2019] [Revised: 08/02/2019] [Accepted: 08/05/2019] [Indexed: 12/15/2022] Open
Affiliation(s)
- Maria Zulfiqar
- Mallinckrodt Institute of RadiologyWashington University School of Medicine St Louis Missouri USA
| | - Claude B. Sirlin
- Department of RadiologyUniversity of California San Diego San Diego California USA
| | | | - Maxime Ronot
- Department of RadiologyHôpitaux Universitaires Paris Nord Val de Seine, Cinchy France
| | | | - Victoria Chernyak
- Department of Radiology, Montefiore Medical CenterAlbert Einstein College of Medicine New York New York USA
| | - Osamu Matsui
- Department of RadiologyKanazawa University Japan
| | - Nina Bastati
- Department of Biomedical Imaging and Image‐guided therapyMedical University of Vienna Vienna Austria
| | - Ahmed Ba‐Ssalamah
- Department of Biomedical Imaging and Image‐guided therapyMedical University of Vienna Vienna Austria
| | - Deyali Chatterjee
- Department of PathologyWashington University School of Medicine St Louis Missouri USA
| | - Mustafa Bashir
- Department of RadiologyDuke University Durham North Carolina USA
| | - Kathryn J. Fowler
- Department of RadiologyUniversity of California San Diego San Diego California USA
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Cannella R, Brancatelli G, Rangaswamy B, Minervini MI, Borhani AA, Furlan A. Enhancement pattern of hepatocellular adenoma (HCA) on MR imaging performed with Gd-EOB-DTPA versus other Gd-based contrast agents (GBCAs): An intraindividual comparison. Eur J Radiol 2019; 119:108633. [PMID: 31437747 DOI: 10.1016/j.ejrad.2019.08.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2019] [Revised: 07/20/2019] [Accepted: 08/05/2019] [Indexed: 01/28/2023]
Abstract
PURPOSE To conduct an intraindividual comparison of the enhancement pattern of hepatocellular adenoma (HCA) on dynamic MRI study obtained following the injection of Gadoxetic acid (Gd-EOB-DTPA) and other gadolinium-based contrast agents (GBCAs). METHOD This is a retrospective, Institutional Review Board-approved study conducted in a single institution. A search of medical records between 2008 and 2017 revealed 17 patients (all females) with at least one pathologically-proven HCA who underwent liver MRI with Gd-EOB-DTPA and another GBCA within 1 year. Enhancement of each lesion on hepatic arterial (HAP), portal venous (PVP), 2 min and 4-5 minutes phases was subjectively evaluated by two abdominal radiologists. Lesions were categorized as hyper-, iso- or hypointense compared to the surrounding liver parenchyma. The presence of a peripheral pseudocapsule was also recorded. The differences in lesion enhancement were assessed using the McNemar Test. A p-value <0.05 was considered statistically significant. RESULTS The final population included 35 HCAs (83% inflammatory subtype). There was no significant difference in lesion size (P = 0.708) and enhancement on HAP (P = 0.625) or PVP (P = 0.125). HCAs showed more frequently hypointensity on 2 min (13/35 vs. 1/35, P < 0.001) and 4-5 minutes (P < 0.001) images obtained after injection of Gd-EOB-DTPA compared to those obtained after other GBCAs. A pseudocapsule was more frequently noted after administration of Gd-EOB-DTPA (13/35 vs 1/35, P = 0.002). CONCLUSIONS Enhancement pattern of HCA differs significantly after the injection of Gd-EOB-DTPA compared to other GBCAs. Lesion hypointensity on 2 min and 4-5 minutes images is more frequent when using Gd-EOB-DTPA.
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Affiliation(s)
- Roberto Cannella
- Abdominal Imaging Division, Department of Radiology, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA, 15213, USA; Section of Radiology - BiND., University Hospital "Paolo Giaccone", Via del Vespro 129, 90127, Palermo, Italy
| | - Giuseppe Brancatelli
- Section of Radiology - BiND., University Hospital "Paolo Giaccone", Via del Vespro 129, 90127, Palermo, Italy
| | - Balasubramanya Rangaswamy
- Abdominal Imaging Division, Department of Radiology, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA, 15213, USA
| | - Marta I Minervini
- Division of Transplant Pathology, Department of Pathology, UPMC Montefiore, University of Pittsburgh, PA, United States
| | - Amir A Borhani
- Abdominal Imaging Division, Department of Radiology, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA, 15213, USA
| | - Alessandro Furlan
- Abdominal Imaging Division, Department of Radiology, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA, 15213, USA.
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Abstract
INTRODUCTION Surgery is advocated in hepatocellular adenomas (HCA) >5 cm that do not regress to <5 cm after 6-12 months. The aim of this study was to develop a model for these patients, estimating the probability of HCA regression to <5 cm at 1 and 2 years follow-up. METHODS Data were derived from a multicenter retrospective cohort of female patients diagnosed with HCA >5 cm at first follow-up. Potential predictors included age, body mass index, and HCA diameter at diagnosis (T0), HCA-subtype (hepatocyte nuclear factor 1α inactivated HCA, inflammatory-HCA, unclassified HCA) and "T0-T1 regression-over-time" (percentage of regression between T0 and first follow-up (T1) divided by weeks between T0 and T1). Cox proportional hazards regression was used to develop a multivariable model with time to regression of HCA < 5 cm as outcome. Probabilities at 1 and 2 years follow-up were calculated. RESULTS In total, 180 female patients were included. Median HCA diameter at T0 was 82.0 mm and at T1 65.0 mm. Eighty-one patients (45%) reached the clinical endpoint of regression to <5 cm after a median of 34 months. No complications occurred during follow-up. In multivariable analysis, the strongest predictors for regression to <5 cm were HCA diameter at T0 (logtransformed, hazard ratio (HR) 0.05), T0-T1 regression-over-time (HR 2.15) and HCA subtype inflammatory-HCA (HR 2.93) and unclassified HCA (HR 2.40), compared to hepatocyte nuclear factor 1α inactivated HCA (reference). The model yielded an internally validated c-index of 0.79. DISCUSSION In patients diagnosed with HCA > 5 cm that still exceed 5 cm at first follow-up, regression to <5 cm can be predicted at 1 and 2 years follow-up using this model. Although external validation in an independent population is required, this model may aid in decision-making and potentially avoid unnecessary surgery.
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Abstract
OBJECTIVE To describe the MRI findings of the effects of exogenous sex steroids on the liver. FINDINGS Estrogens, progesterone and synthetic testosterone are exogenous sex steroids that may result in a variety of liver diseases, including tumour formation and vascular disorders. These hormones are mainly administered in the form of the oral contraceptive pill (OCP) and anabolic steroids. Both are implicated in hepatic adenoma formation. The HNF-1α-mutated and inflammatory adenoma subgroups are more commonly seen in association with the OCP whereas there is an increased incidence of the β-catenin positive subtype with anabolic steroid use. Furthermore, anabolic steroids are associated with hepatocellular carcinoma resulting from malignant transformation of β-catenin positive adenomas. The oral contraceptive pill may also induce vascular disorders within the liver, some of which are related to the prothrombotic effect of the hormones, such as hepatic and portal vein thrombosis. Other hepatic vascular abnormalities resulting from exogenous sex steroids include veno-occlusive disease and peliosis hepatis.
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Glinka J, Clariá RS, Fratanoni E, Spina J, Mullen E, Ardiles V, Mazza O, Pekolj J, de Santibañes M, de Santibañes E. Malignant transformation of hepatocellular adenoma in a young female patient after ovulation induction fertility treatment: A case report. World J Gastrointest Surg 2019; 11:229-236. [PMID: 31123560 PMCID: PMC6513787 DOI: 10.4240/wjgs.v11.i4.229] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2019] [Revised: 04/17/2019] [Accepted: 04/23/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hepatocellular adenoma (HCA) is a rare benign liver tumor usually affecting young women with a history of prolonged use of hormonal contraception. Although the majority is asymptomatic, a low proportion may have significant complications such as bleeding or malignancy. Despite responding to the hormonal stimulus, the desire for pregnancy in patients with small HCA is not contraindicated. However, through this work we demonstrate that intensive hormonal therapies such as those used in the treatment of infertility can trigger serious complications
CASE SUMMARY A 33-year-old female with a 10-year history of oral contraceptive use was diagnosed with a hepatic tumor as an incidental finding in an abdominal ultrasound. The patient showed no symptoms and physical examination was unremarkable. Laboratory functional tests were within normal limits and tests for serum tumor markers were negative. An abdominal magnetic resonance imaging (MRI) was performed, showing a 30 mm × 29 mm focal lesion in segment VI of the liver compatible with HCA or Focal Nodular Hyperplasia with atypical behavior. After a total of six years of follow-up, the patient underwent ovulation induction treatment for infertility. On a following MRI, a suspected malignancy was warned and hence, surgery was decided. The surgical specimen revealed malignant transformation of HCA towards trabecular hepatocarcinoma with dedifferentiated areas. There was non-evidence of tumor recurrence after three years of clinical and imaging follow-up.
CONCLUSION HCAs can be malignant regardless its size and low-risk appearance on MRI when an ovultation induction therapy is indicated.
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Affiliation(s)
- Juan Glinka
- Department of General Surgery, Hepato-bilio-pancreatic Unit, Hospital Italiano de Buenos Aires, Buenos Aires C1181ACH, Argentina
| | - Rodrigo Sanchez Clariá
- Department of General Surgery, Hepato-bilio-pancreatic Unit, Hospital Italiano de Buenos Aires, Buenos Aires C1181ACH, Argentina
| | - Eugenia Fratanoni
- Department of General Surgery, Hepato-bilio-pancreatic Unit, Hospital Italiano de Buenos Aires, Buenos Aires C1181ACH, Argentina
| | - Juan Spina
- Department of Radiology, Hospital Italiano de Buenos Aires, Buenos Aires C1181ACH, Argentina
| | - Eduardo Mullen
- Department of Surgical Pathology, Hospital Italiano de Buenos Aires, Buenos Aires C1181ACH, Argentina
| | - Victoria Ardiles
- Department of General Surgery, Hepato-bilio-pancreatic Unit, Hospital Italiano de Buenos Aires, Buenos Aires C1181ACH, Argentina
| | - Oscar Mazza
- Department of General Surgery, Hepato-bilio-pancreatic Unit, Hospital Italiano de Buenos Aires, Buenos Aires C1181ACH, Argentina
| | - Juan Pekolj
- Department of General Surgery, Hepato-bilio-pancreatic Unit, Hospital Italiano de Buenos Aires, Buenos Aires C1181ACH, Argentina
| | - Martín de Santibañes
- Department of General Surgery, Hepato-bilio-pancreatic Unit, Hospital Italiano de Buenos Aires, Buenos Aires C1181ACH, Argentina
| | - Eduardo de Santibañes
- Department of General Surgery, Hepato-bilio-pancreatic Unit, Hospital Italiano de Buenos Aires, Buenos Aires C1181ACH, Argentina
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