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Yang MC, Liu HY, Zhang YM, Guo Y, Yang SY, Zhang HW, Cui B, Zhou TM, Guo HX, Hou DW. The diagnostic value of a nomogram based on enhanced CT radiomics for differentiating between intrahepatic cholangiocarcinoma and early hepatic abscess. Front Mol Biosci 2024; 11:1409060. [PMID: 39247207 PMCID: PMC11377335 DOI: 10.3389/fmolb.2024.1409060] [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] [Received: 03/29/2024] [Accepted: 08/08/2024] [Indexed: 09/10/2024] Open
Abstract
Objective This study aimed to investigate the value of a CT-enhanced scanning radiomics nomogram in distinguishing between early hepatic abscess (EHA) and intrahepatic cholangiocarcinoma (ICC) and to validate its diagnostic efficacy. Materials and Methods Clinical and imaging data on 112 patients diagnosed with EHA and ICC who underwent double-phase CT-enhanced scanning at our hospital were collected. The contours of the lesions were delineated layer by layer across the three phases of CT scanning and enhancement using 3D Slicer software to define the region of interest (ROI). Subsequently, the contours were merged into 3D models, and radiomics features were extracted using the Radiomics plug-in. The data were randomly divided into training (n = 78) and validation (n = 34) cohorts at a 7:3 ratio, using the R programming language. Standardization was performed using the Z-score method, and LASSO regression was used to select the best λ-value for screening variables, which were then used to establish prediction models. The rad-score was calculated using the best radiomics model, and a joint model was constructed based on the rad-score and clinical scores. A nomogram was developed based on the joint model. The diagnostic efficacy of the models for distinguishing ICC and EHA was assessed using receiver operating characteristic (ROC) curve and area under the curve (AUC) analyses. Calibration curves were used to evaluate the reliability and accuracy of the nomograms, while decision curves and clinical impact curves were utilized to assess their clinical value. Results Compared with the ICC group, significant differences were observed in clinical data and imaging characteristics in the EHA group, including age, centripetal enhancement, hepatic pericardial depression sign, arterial perfusion abnormality, arterial CT value, and arteriovenous enhancement (p < 0.05). Logistic regression analysis identified centripetal enhancement, hepatic pericardial depression sign, arterial perfusion abnormality, arterial CT value, and arteriovenous enhancement as independent influencing factors. Three, five, and four radiomics features were retained in the scanning, arterial, and venous phases, respectively. Single-phase models were constructed, with the radiomics model from the arterial phase demonstrating the best diagnostic efficacy. The rad-score was calculated using the arterial-phase radiomics model, and nomograms were drawn in conjunction with the clinical model. The nomogram based on the combined model exhibited the highest differential diagnostic efficacy between EHA and ICC (training cohort: AUC of 0.972; validation cohort: AUC of 0.868). The calibration curves indicated good agreement between the predicted and pathological results, while decision curves and clinical impact curves demonstrated higher clinical utility of the nomograms. Conclusion The CT-enhanced scanning radiomics nomogram demonstrates high clinical value in distinguishing between EHA and ICC, thereby enhancing the accuracy of preoperative diagnosis.
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Affiliation(s)
- Meng-Chen Yang
- Department of Medical Imaging, Shangluo Central Hospital, Shangluo, China
| | - Hai-Yang Liu
- Department of Medical Imaging, Shangluo Central Hospital, Shangluo, China
| | - Yan-Ming Zhang
- Department of Medical Imaging, Shangluo Central Hospital, Shangluo, China
| | - Yi Guo
- Department of Medical Imaging, Shangluo Central Hospital, Shangluo, China
| | - Shang-Yu Yang
- Department of Medical Imaging, Shangluo Central Hospital, Shangluo, China
| | - Hua-Wei Zhang
- Department of Medical Imaging, Shangluo Central Hospital, Shangluo, China
| | - Bao Cui
- Department of Medical Imaging, Shangluo Central Hospital, Shangluo, China
| | - Tian-Min Zhou
- Department of Medical Imaging, Shangluo Central Hospital, Shangluo, China
| | - Hao-Xiang Guo
- Department of Medical Imaging, Shangluo Central Hospital, Shangluo, China
| | - Dan-Wei Hou
- Department of Medical Imaging, Shangluo Central Hospital, Shangluo, China
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Evans M, Kendall T. Practical considerations for pathological diagnosis and molecular profiling of cholangiocarcinoma: an expert review for best practices. Expert Rev Mol Diagn 2024; 24:393-408. [PMID: 38752560 DOI: 10.1080/14737159.2024.2353696] [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: 02/12/2024] [Accepted: 05/07/2024] [Indexed: 05/22/2024]
Abstract
INTRODUCTION Advances in precision medicine have expanded access to targeted therapies and demand for molecular profiling of cholangiocarcinoma (CCA) patients in routine clinical practice. However, pathologists face challenges in establishing a definitive intrahepatic CCA (iCCA) diagnosis while preserving sufficient tissue for molecular profiling. Additionally, they frequently face challenges in optimal tissue handling to preserve nucleic acid integrity. AREAS COVERED This article first identifies the challenges in establishing a definitive diagnosis of iCCA in a lesional liver biopsy while preserving sufficient tissue for molecular profiling. Then, the authors explore the clinical value of molecular profiling, the basic principles of single gene and next-generation sequencing (NGS) techniques, and the challenges in tissue sampling for genomic testing. They also propose an algorithm for best practice in tissue management for molecular profiling of CCA. EXPERT OPINION Several practical challenges face pathologists during tissue sampling and processing for molecular profiling. Optimized tissue processing, careful tissue handling, and selection of appropriate approaches to molecular testing are essential to ensure that the highest possible quality of diagnostic information is provided in the greatest proportion of cases.
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Affiliation(s)
- Matt Evans
- Cellular Pathologist, University Hospital Southampton NHS Foundation Trust, Southampton, UK
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Heumann P, Albert A, Gülow K, Tümen D, Müller M, Kandulski A. Current and Future Therapeutic Targets for Directed Molecular Therapies in Cholangiocarcinoma. Cancers (Basel) 2024; 16:1690. [PMID: 38730642 PMCID: PMC11083102 DOI: 10.3390/cancers16091690] [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: 03/25/2024] [Revised: 04/17/2024] [Accepted: 04/21/2024] [Indexed: 05/13/2024] Open
Abstract
We conducted a comprehensive review of the current literature of published data, clinical trials (MEDLINE; ncbi.pubmed.com), congress contributions (asco.org; esmo.org), and active recruiting clinical trains (clinicaltrial.gov) on targeted therapies in cholangiocarcinoma. Palliative treatment regimens were analyzed as well as preoperative and perioperative treatment options. We summarized the current knowledge for each mutation and molecular pathway that is or has been under clinical evaluation and discussed the results on the background of current treatment guidelines. We established and recommended targeted treatment options that already exist for second-line settings, including IDH-, BRAF-, and NTRK-mutated tumors, as well as for FGFR2 fusion, HER2/neu-overexpression, and microsatellite instable tumors. Other options for targeted treatment include EGFR- or VEGF-dependent pathways, which are known to be overexpressed or dysregulated in this cancer type and are currently under clinical investigation. Targeted therapy in CCA is a hallmark of individualized medicine as these therapies aim to specifically block pathways that promote cancer cell growth and survival, leading to tumor shrinkage and improved patient outcomes based on the molecular profile of the tumor.
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Affiliation(s)
- Philipp Heumann
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology, and Infectious Diseases University Hospital Regensburg Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany
| | | | | | | | | | - Arne Kandulski
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology, and Infectious Diseases University Hospital Regensburg Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany
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Wang J, Guan X, Shang N, Wu D, Liu Z, Guan Z, Zhang Z, Jin Z, Wei X, Liu X, Song M, Zhu W, Dai G. Dysfunction of CCT3-associated network signals for the critical state during progression of hepatocellular carcinoma. Biochim Biophys Acta Mol Basis Dis 2024; 1870:167054. [PMID: 38360074 DOI: 10.1016/j.bbadis.2024.167054] [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: 08/24/2023] [Revised: 01/25/2024] [Accepted: 01/30/2024] [Indexed: 02/17/2024]
Abstract
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors and is a serious threat to human health; thus, early diagnosis and adequate treatment are essential. However, there are still great challenges in identifying the tipping point and detecting early warning signals of early HCC. In this study, we aimed to identify the tipping point (critical state) of and key molecules involved in hepatocarcinogenesis based on time series transcriptome expression data of HCC patients. The phase from veHCC (very early HCC) to eHCC (early HCC) was identified as the critical state in HCC progression, with 143 genes identified as key candidate molecules by combining the DDRTree (dimensionality reduction via graph structure learning) and DNB (dynamic network biomarker) methods. Then, we ranked the candidate genes to verify their mRNA levels using the diethylnitrosamine (DEN)-induced HCC mouse model and identified five early warning signals, namely, CCT3, DSTYK, EIF3E, IARS2 and TXNRD1; these signals can be regarded as the potential early warning signals for the critical state of HCC. We identified CCT3 as an independent prognostic factor for HCC, and functions of CCT3 involving in the "MYCtargets_V1" and "E2F-Targets" are closely related to the progression of HCC. The predictive method combining the DDRTree and DNB methods can not only identify the key critical state before cancer but also determine candidate molecules of critical state, thus providing new insight into the early diagnosis and preemptive treatment of HCC.
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Affiliation(s)
- Jianwei Wang
- School of Computer and Artificial Intelligence, Zhengzhou University, Zhengzhou 45001, China; School of Life Sciences, Zhengzhou University, Zhengzhou 45001, China
| | - Xiaowen Guan
- School of Life Sciences, Zhengzhou University, Zhengzhou 45001, China
| | - Ning Shang
- School of Life Sciences, Zhengzhou University, Zhengzhou 45001, China
| | - Di Wu
- School of Life Sciences, Zhengzhou University, Zhengzhou 45001, China
| | - Zihan Liu
- School of Life Sciences, Zhengzhou University, Zhengzhou 45001, China
| | - Zhenzhen Guan
- School of Life Sciences, Zhengzhou University, Zhengzhou 45001, China
| | - Zhizi Zhang
- School of Life Sciences, Zhengzhou University, Zhengzhou 45001, China
| | - Zhongzhen Jin
- School of Life Sciences, Zhengzhou University, Zhengzhou 45001, China
| | - Xiaoyi Wei
- School of Life Sciences, Zhengzhou University, Zhengzhou 45001, China
| | - Xiaoran Liu
- School of Life Sciences, Zhengzhou University, Zhengzhou 45001, China
| | - Mingzhu Song
- School of Life Sciences, Zhengzhou University, Zhengzhou 45001, China
| | - Weijun Zhu
- School of Computer and Artificial Intelligence, Zhengzhou University, Zhengzhou 45001, China.
| | - Guifu Dai
- School of Life Sciences, Zhengzhou University, Zhengzhou 45001, China.
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Bragazzi MC, Venere R, Ribichini E, Covotta F, Cardinale V, Alvaro D. Intrahepatic cholangiocarcinoma: Evolving strategies in management and treatment. Dig Liver Dis 2024; 56:383-393. [PMID: 37722960 DOI: 10.1016/j.dld.2023.08.052] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Revised: 08/07/2023] [Accepted: 08/21/2023] [Indexed: 09/20/2023]
Abstract
Intrahepatic cholangiocarcinoma is the second most frequent primary liver cancer after hepatocellular carcinoma. According to International Classification of Diseases-11 (ICD-11), intrahepatic cholangiocarcinoma is identified by a specific diagnostic code, different with respect to perihilar-CCA or distal-CCA. Intrahepatic cholangiocarcinoma originates from intrahepatic small or large bile ducts including the second-order bile ducts and has a silent presentation that combined with the highly aggressive nature and refractoriness to chemotherapy contributes to the alarming increasing incidence and mortality. Indeed, at the moment of the diagnosis, less than 40% of intrahepatic cholangiocarcinoma are suitable of curative surgical therapy, that is so far the only effective treatment. The main goals of clinicians and researchers are to make an early diagnosis, and to carry out molecular characterization to provide the patient with personalized treatment. Unfortunately, these goals are not easily achievable because of the heterogeneity of this tumor from anatomical, molecular, biological, and clinical perspectives. However, recent progress has been made in molecular characterization, surgical treatment, and management of intrahepatic cholangiocarcinoma and, this article deals with these advances.
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Affiliation(s)
- Maria Consiglia Bragazzi
- Department of Medical-Surgical Sciences and Biotechnology, Sapienza University of Rome Polo Pontino, Italy.
| | - Rosanna Venere
- Department of Medical-Surgical Sciences and Biotechnology, Sapienza University of Rome Polo Pontino, Italy
| | - Emanuela Ribichini
- Department Translational and Precision, Sapienza University of Rome, Italy
| | - Francesco Covotta
- Department Translational and Precision, Sapienza University of Rome, Italy
| | - Vincenzo Cardinale
- Department Translational and Precision, Sapienza University of Rome, Italy
| | - Domenico Alvaro
- Department Translational and Precision, Sapienza University of Rome, Italy
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Huang X, Yu D, Gu X, Li J, Chen J, Zou Y, Liao J. A comparative study of clinicopathological and imaging features of HBV-negative and HBV-positive intrahepatic cholangiocarcinoma patients with different pathologic differentiation degrees. Sci Rep 2023; 13:19726. [PMID: 37957323 PMCID: PMC10643568 DOI: 10.1038/s41598-023-47108-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Accepted: 11/09/2023] [Indexed: 11/15/2023] Open
Abstract
Hepatitis B is a risk factor for the development of intrahepatic cholangiocarcinoma. The prognosis of HBV-related ICC remains to be further investigated. To investigate the clinical, pathological and imaging features of intrahepatic cholangiocarcinoma of hepatitis B virus-positive and -negative patients. Data from January 31, 2012 to December 31, 2019 of 138 patients were retrospectively analyzed. The patients were divided into hepatitis B virus-positive group (group A[n = 66]) and virus-negative group (group B[n = 72]), and the patients were divided into groups according to pathological differentiation degree and tumor size. The differences in clinical, imaging characteristics and the progression-free survival between groups were analyzed. There were significant differences in gender, age, HBc antibody, CA125 and AFP, tumor distribution site, maximum diameter, plain scan density, inferior hepatic angle, peritumoral bile duct dilatation, vascular encasement invasion, intrahepatic bile duct dilatation and lymphadenopathy between the two groups (P < 0.05); There were statistical differences in signs of vascular encasement invasion between the two groups with well-to-moderately differentiated tumors (P < 0.05); there were statistical differences in tumor density uniformity, signs of vascular encasement invasion and lymphadenopathy between the two groups with poorly differentiated tumors (P < 0.05). Large groups A and B showed differences in tumor density uniformity, vascular encasement invasion, arterial phase, overall reinforcement pattern, peritumoral bile duct stones and biliary dilatation (P < 0.05). There was no statistical difference in postoperative PFS between the two groups (P > 0.05). The clinical and imaging features of ICC of hepatitis B virus-positive and -negative patients are different, and there is little difference in postoperative disease-free survival time.
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Affiliation(s)
- Xiaoli Huang
- Department of Radiology, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, 530021, Guangxi, People's Republic of China
| | - Dan Yu
- Department of Radiology, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, 530021, Guangxi, People's Republic of China
- Department of Radiology, Yulin First People's Hospital, No. 495 Jiaoyuzhong Road, Yulin, 537000, Guangxi, China
| | - Xintao Gu
- Department of Radiology, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, 530021, Guangxi, People's Republic of China
| | - Jiansun Li
- Department of Radiology, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, 530021, Guangxi, People's Republic of China
| | - Jiaqi Chen
- Department of Radiology, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, 530021, Guangxi, People's Republic of China
| | - Yuanqiang Zou
- Department of Radiology, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, 530021, Guangxi, People's Republic of China
| | - Jinyuan Liao
- Department of Radiology, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, 530021, Guangxi, People's Republic of China.
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Liu N, Wu Y, Tao Y, Zheng J, Huang X, Yang L, Zhang X. Differentiation of Hepatocellular Carcinoma from Intrahepatic Cholangiocarcinoma through MRI Radiomics. Cancers (Basel) 2023; 15:5373. [PMID: 38001633 PMCID: PMC10670473 DOI: 10.3390/cancers15225373] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Revised: 10/25/2023] [Accepted: 11/06/2023] [Indexed: 11/26/2023] Open
Abstract
The purpose of this study was to investigate the efficacy of magnetic resonance imaging (MRI) radiomics in differentiating hepatocellular carcinoma (HCC) from intrahepatic cholangiocarcinoma (ICC). The clinical and MRI data of 129 pathologically confirmed HCC patients and 48 ICC patients treated at the Affiliated Hospital of North Sichuan Medical College between April 2016 and December 2021 were retrospectively analyzed. The patients were randomly divided at a ratio of 7:3 into a training group of 124 patients (90 with HCC and 34 with ICC) and a validation group of 53 patients (39 with HCC and 14 with ICC). Radiomic features were extracted from axial fat suppression T2-weighted imaging (FS-T2WI) and axial arterial-phase (AP) and portal-venous-phase (PVP) dynamic-contrast-enhanced MRI (DCE-MRI) sequences, and the corresponding datasets were generated. The least absolute shrinkage and selection operator (LASSO) method was used to select the best radiomic features. Logistic regression was used to establish radiomic models for each sequence (FS-T2WI, AP and PVP models), a clinical model for optimal clinical variables (C model) and a joint radiomics model (JR model) integrating the radiomics features of all the sequences as well as a radiomics-clinical model combining optimal radiomic features and clinical risk factors (RC model). The performance of each model was evaluated using the area under the receiver operating characteristic curve (AUC). The AUCs of the FS-T2WI, AP, PVP, JR, C and RC models for distinguishing HCC from ICC were 0.693, 0.863, 0.818, 0.914, 0.936 and 0.977 in the training group and 0.690, 0.784, 0.727, 0.802, 0.860 and 0.877 in the validation group, respectively. The results of this study suggest that MRI-based radiomics may help noninvasively differentiate HCC from ICC. The model integrating the radiomics features and clinical risk factors showed a further improvement in performance.
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Affiliation(s)
- Ning Liu
- Medical Imaging Key Laboratory of Sichuan Province, Interventional Medical Center, Department of Radiology, Medical Research Center, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China; (N.L.); (Y.W.); (Y.T.); (J.Z.); (X.H.); (X.Z.)
- Hospital of Chengdu Office of People’s Government of Tibetan Autonomous Region (Hospital. C.T.), Chengdu 610041, China
| | - Yaokun Wu
- Medical Imaging Key Laboratory of Sichuan Province, Interventional Medical Center, Department of Radiology, Medical Research Center, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China; (N.L.); (Y.W.); (Y.T.); (J.Z.); (X.H.); (X.Z.)
| | - Yunyun Tao
- Medical Imaging Key Laboratory of Sichuan Province, Interventional Medical Center, Department of Radiology, Medical Research Center, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China; (N.L.); (Y.W.); (Y.T.); (J.Z.); (X.H.); (X.Z.)
| | - Jing Zheng
- Medical Imaging Key Laboratory of Sichuan Province, Interventional Medical Center, Department of Radiology, Medical Research Center, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China; (N.L.); (Y.W.); (Y.T.); (J.Z.); (X.H.); (X.Z.)
| | - Xiaohua Huang
- Medical Imaging Key Laboratory of Sichuan Province, Interventional Medical Center, Department of Radiology, Medical Research Center, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China; (N.L.); (Y.W.); (Y.T.); (J.Z.); (X.H.); (X.Z.)
| | - Lin Yang
- Medical Imaging Key Laboratory of Sichuan Province, Interventional Medical Center, Department of Radiology, Medical Research Center, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China; (N.L.); (Y.W.); (Y.T.); (J.Z.); (X.H.); (X.Z.)
| | - Xiaoming Zhang
- Medical Imaging Key Laboratory of Sichuan Province, Interventional Medical Center, Department of Radiology, Medical Research Center, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China; (N.L.); (Y.W.); (Y.T.); (J.Z.); (X.H.); (X.Z.)
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Shahbazian H, Mirza-Aghazadeh-Attari M, Borhani A, Mohseni A, Madani SP, Ansari G, Pawlik TM, Kamel IR. Multimodality imaging of hepatocellular carcinoma and intrahepatic cholangiocarcinoma. J Surg Oncol 2023; 128:519-530. [PMID: 37439096 DOI: 10.1002/jso.27396] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Revised: 07/03/2023] [Accepted: 07/04/2023] [Indexed: 07/14/2023]
Abstract
Hepatocellular carcinoma and intrahepatic cholangiocarcinoma are the two most common primary malignant tumors of the liver. The similarities and variations in imaging characteristics that may aid in distinguishing between these two primary tumors will be discussed and outlined in this review. Knowledge of imaging techniques that are currently available would assist in the differentiation between these primary malignancies.
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Affiliation(s)
- Haneyeh Shahbazian
- Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Mohammad Mirza-Aghazadeh-Attari
- Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Ali Borhani
- Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Alireza Mohseni
- Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Seyedeh Panid Madani
- Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Golnoosh Ansari
- Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center, and James Cancer Center, Columbus, Ohio, USA
| | - Ihab R Kamel
- Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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Alvaro D, Gores GJ, Walicki J, Hassan C, Sapisochin G, Komuta M, Forner A, Valle JW, Laghi A, Ilyas SI, Park JW, Kelley RK, Reig M, Sangro B. EASL-ILCA Clinical Practice Guidelines on the management of intrahepatic cholangiocarcinoma. J Hepatol 2023; 79:181-208. [PMID: 37084797 DOI: 10.1016/j.jhep.2023.03.010] [Citation(s) in RCA: 88] [Impact Index Per Article: 44.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2023] [Accepted: 03/10/2023] [Indexed: 04/23/2023]
Abstract
Intrahepatic cholangiocarcinoma (iCCA) develops inside the liver, between bile ductules and the second-order bile ducts. It is the second most frequent primary liver cancer after hepatocellular carcinoma, and its global incidence is increasing. It is associated with an alarming mortality rate owing to its silent presentation (often leading to late diagnosis), highly aggressive nature and resistance to treatment. Early diagnosis, molecular characterisation, accurate staging and personalised multidisciplinary treatments represent current challenges for researchers and physicians. Unfortunately, these challenges are beset by the high heterogeneity of iCCA at the clinical, genomic, epigenetic and molecular levels, very often precluding successful management. Nonetheless, in the last few years, progress has been made in molecular characterisation, surgical management, and targeted therapy. Recent advances together with the awareness that iCCA represents a distinct entity amongst the CCA family, led the ILCA and EASL governing boards to commission international experts to draft dedicated evidence-based guidelines for physicians involved in the diagnostic, prognostic, and therapeutic management of iCCA.
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Cerrito L, Ainora ME, Borriello R, Piccirilli G, Garcovich M, Riccardi L, Pompili M, Gasbarrini A, Zocco MA. Contrast-Enhanced Imaging in the Management of Intrahepatic Cholangiocarcinoma: State of Art and Future Perspectives. Cancers (Basel) 2023; 15:3393. [PMID: 37444503 PMCID: PMC10341250 DOI: 10.3390/cancers15133393] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2023] [Revised: 06/23/2023] [Accepted: 06/25/2023] [Indexed: 07/15/2023] Open
Abstract
Intrahepatic cholangiocarcinoma (iCCA) represents the second most common liver cancer after hepatocellular carcinoma, accounting for 15% of primary liver neoplasms. Its incidence and mortality rate have been rising during the last years, and total new cases are expected to increase up to 10-fold during the next two or three decades. Considering iCCA's poor prognosis and rapid spread, early diagnosis is still a crucial issue and can be very challenging due to the heterogeneity of tumor presentation at imaging exams and the need to assess a correct differential diagnosis with other liver lesions. Abdominal contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) plays an irreplaceable role in the evaluation of liver masses. iCCA's most typical imaging patterns are well-described, but atypical features are not uncommon at both CT and MRI; on the other hand, contrast-enhanced ultrasound (CEUS) has shown a great diagnostic value, with the interesting advantage of lower costs and no renal toxicity, but there is still no agreement regarding the most accurate contrastographic patterns for iCCA detection. Besides diagnostic accuracy, all these imaging techniques play a pivotal role in the choice of the therapeutic approach and eligibility for surgery, and there is an increasing interest in the specific imaging features which can predict tumor behavior or histologic subtypes. Further prognostic information may also be provided by the extraction of quantitative data through radiomic analysis, creating prognostic multi-parametric models, including clinical and serological parameters. In this review, we aim to summarize the role of contrast-enhanced imaging in the diagnosis and management of iCCA, from the actual issues in the differential diagnosis of liver masses to the newest prognostic implications.
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Affiliation(s)
| | - Maria Elena Ainora
- CEMAD Digestive Disease Center, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (L.C.); (R.B.); (G.P.); (M.G.); (L.R.); (M.P.); (A.G.); (M.A.Z.)
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Moris D, Palta M, Kim C, Allen PJ, Morse MA, Lidsky ME. Advances in the treatment of intrahepatic cholangiocarcinoma: An overview of the current and future therapeutic landscape for clinicians. CA Cancer J Clin 2023; 73:198-222. [PMID: 36260350 DOI: 10.3322/caac.21759] [Citation(s) in RCA: 217] [Impact Index Per Article: 108.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2022] [Revised: 08/25/2022] [Accepted: 08/29/2022] [Indexed: 01/27/2023] Open
Abstract
Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver tumor and remains a fatal malignancy in the majority of patients. Approximately 20%-30% of patients are eligible for resection, which is considered the only potentially curative treatment; and, after resection, a median survival of 53 months has been reported when sequenced with adjuvant capecitabine. For the 70%-80% of patients who present with locally unresectable or distant metastatic disease, systemic therapy may delay progression, but survival remains limited to approximately 1 year. For the past decade, doublet chemotherapy with gemcitabine and cisplatin has been considered the most effective first-line regimen, but results from the recent use of triplet regimens and even immunotherapy may shift the paradigm. More effective treatment strategies, including those that combine systemic therapy with locoregional therapies like radioembolization or hepatic artery infusion, have also been developed. Molecular therapies, including those that target fibroblast growth factor receptor and isocitrate dehydrogenase, have recently received US Food and Drug Administration approval for a defined role as second-line treatment for up to 40% of patients harboring these actionable genomic alterations, and whether they should be considered in the first-line setting is under investigation. Furthermore, as the oncology field seeks to expand indications for immunotherapy, recent data demonstrated that combining durvalumab with standard cytotoxic therapy improved survival in patients with ICC. This review focuses on the current and future strategies for ICC treatment, including a summary of the primary literature for each treatment modality and an algorithm that can be used to drive a personalized and multidisciplinary approach for patients with this challenging malignancy.
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Affiliation(s)
- Dimitrios Moris
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA
| | - Manisha Palta
- Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina, USA
| | - Charles Kim
- Department of Radiology, Duke University Medical Center, Durham, North Carolina, USA
| | - Peter J Allen
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA
| | - Michael A Morse
- Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA
| | - Michael E Lidsky
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA
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Bakrania A, Joshi N, Zhao X, Zheng G, Bhat M. Artificial intelligence in liver cancers: Decoding the impact of machine learning models in clinical diagnosis of primary liver cancers and liver cancer metastases. Pharmacol Res 2023; 189:106706. [PMID: 36813095 DOI: 10.1016/j.phrs.2023.106706] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2023] [Revised: 02/17/2023] [Accepted: 02/19/2023] [Indexed: 02/22/2023]
Abstract
Liver cancers are the fourth leading cause of cancer-related mortality worldwide. In the past decade, breakthroughs in the field of artificial intelligence (AI) have inspired development of algorithms in the cancer setting. A growing body of recent studies have evaluated machine learning (ML) and deep learning (DL) algorithms for pre-screening, diagnosis and management of liver cancer patients through diagnostic image analysis, biomarker discovery and predicting personalized clinical outcomes. Despite the promise of these early AI tools, there is a significant need to explain the 'black box' of AI and work towards deployment to enable ultimate clinical translatability. Certain emerging fields such as RNA nanomedicine for targeted liver cancer therapy may also benefit from application of AI, specifically in nano-formulation research and development given that they are still largely reliant on lengthy trial-and-error experiments. In this paper, we put forward the current landscape of AI in liver cancers along with the challenges of AI in liver cancer diagnosis and management. Finally, we have discussed the future perspectives of AI application in liver cancer and how a multidisciplinary approach using AI in nanomedicine could accelerate the transition of personalized liver cancer medicine from bench side to the clinic.
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Affiliation(s)
- Anita Bakrania
- Toronto General Hospital Research Institute, Toronto, ON, Canada; Ajmera Transplant Program, University Health Network, Toronto, ON, Canada; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
| | | | - Xun Zhao
- Toronto General Hospital Research Institute, Toronto, ON, Canada; Ajmera Transplant Program, University Health Network, Toronto, ON, Canada
| | - Gang Zheng
- Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada; Institute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada
| | - Mamatha Bhat
- Toronto General Hospital Research Institute, Toronto, ON, Canada; Ajmera Transplant Program, University Health Network, Toronto, ON, Canada; Division of Gastroenterology, Department of Medicine, University Health Network and University of Toronto, Toronto, ON, Canada; Department of Medical Sciences, Toronto, ON, Canada.
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Bowlus CL, Arrivé L, Bergquist A, Deneau M, Forman L, Ilyas SI, Lunsford KE, Martinez M, Sapisochin G, Shroff R, Tabibian JH, Assis DN. AASLD practice guidance on primary sclerosing cholangitis and cholangiocarcinoma. Hepatology 2023; 77:659-702. [PMID: 36083140 DOI: 10.1002/hep.32771] [Citation(s) in RCA: 125] [Impact Index Per Article: 62.5] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Accepted: 07/26/2022] [Indexed: 01/28/2023]
Affiliation(s)
- Christopher L Bowlus
- Division of Gastroenterology , University of California Davis Health , Sacramento , California , USA
| | | | - Annika Bergquist
- Karolinska Institutet , Karolinska University Hospital , Stockholm , Sweden
| | - Mark Deneau
- University of Utah , Salt Lake City , Utah , USA
| | - Lisa Forman
- University of Colorado , Aurora , Colorado , USA
| | - Sumera I Ilyas
- Mayo Clinic College of Medicine and Science , Rochester , Minnesota , USA
| | - Keri E Lunsford
- Rutgers University-New Jersey Medical School , Newark , New Jersey , USA
| | - Mercedes Martinez
- Vagelos College of Physicians and Surgeons , Columbia University , New York , New York , USA
| | | | | | - James H Tabibian
- David Geffen School of Medicine at UCLA , Los Angeles , California , USA
| | - David N Assis
- Yale School of Medicine , New Haven , Connecticut , USA
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Diagnosis of Cholangiocarcinoma. Diagnostics (Basel) 2023; 13:diagnostics13020233. [PMID: 36673043 PMCID: PMC9858255 DOI: 10.3390/diagnostics13020233] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2022] [Revised: 01/03/2023] [Accepted: 01/04/2023] [Indexed: 01/11/2023] Open
Abstract
Cholangiocarcinoma (CCA), a tumor of the bile duct epithelium, is increasing in incidence. CCA remains a highly fatal malignancy because early diagnosis is difficult. Based on its anatomical location, CCA can be categorized into the following three groups: perihilar, intrahepatic, and extrahepatic. Patients with CCA complain of asymptomatic jaundice, weight loss, and right upper quadrant abdominal discomfort. Imaging modalities, including transabdominal ultrasound, computed tomography, and magnetic resonance imaging, play an important role in detecting tumors as well as guiding biopsy procedures and staging workups in CCA. Characteristically, extrahepatic CCA shows abrupt changes in ductal diameter with upstream ductal dilation. Endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) are recommended as the next step in the evaluation of extrahepatic CCA. Tissue is obtained through EUS-FNA or ERCP (biopsy, brush cytology), and therapeutic intervention (such as stent insertion) is performed with ERCP. Moreover, several serum tumor markers (carbohydrate antigen 19-9 and carcinoembryonic antigen) can be useful in diagnosing CCA in some patients.
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Fowler KJ, Bashir MR, Fetzer DT, Kitao A, Lee JM, Jiang H, Kielar AZ, Ronot M, Kamaya A, Marks RM, Elsayes KM, Tang A, Sirlin CB, Chernyak V. Universal Liver Imaging Lexicon: Imaging Atlas for Research and Clinical Practice. Radiographics 2023; 43:e220066. [PMID: 36427260 DOI: 10.1148/rg.220066] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
The use of standardized terms in assessing and reporting disease processes has well-established benefits, such as clear communication between radiologists and other health care providers, improved diagnostic accuracy and reproducibility, and the enhancement and facilitation of research. Recently, the Liver Imaging Reporting and Data System (LI-RADS) Steering Committee released a universal liver imaging lexicon. The current version of the lexicon includes 81 vetted and precisely defined terms that are relevant to acquisition of images using all major liver imaging modalities and contrast agents, as well as lesion- and organ-level features. Most terms in the lexicon are applicable to all patients undergoing imaging of the liver, and only a minority of the terms are strictly intended to be used for patients with high risk factors for hepatocellular carcinoma. This pictorial atlas familiarizes readers with the liver imaging lexicon and includes discussion of general concepts, providing sample definitions, schematics, and clinical examples for a subset of the terms in the liver imaging lexicon. The authors discuss general, technical, and imaging feature terms used commonly in liver imaging, with the goal of illustrating their use for clinical and research applications. Work of the U.S. Government published under an exclusive license with the RSNA. Online supplemental material is available for this article.
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Affiliation(s)
- Kathryn J Fowler
- From the Liver Imaging Group, Department of Radiology, UC San Diego, San Diego, Calif (K.J.F., C.B.S.); Department of Radiology, Duke University Health System, Durham, NC (M.R.B.); Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Tex (D.T.F.); Department of Radiology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan (A.Kitao); Department of Radiology, Seoul National University College of Medicine, Seoul, South Korea (J.M.L.); Department of Radiology, West China Hospital, Sichuan University, Chengdu, China (H.J.); Joint Department of Medical Imaging, University of Toronto, Toronto, Ontario, Canada (A.Z.K.); Department of Radiology, Université Paris Cité, Paris, France, and Department of Radiology, Hôpital Beaujon, APHP.Nord, Clichy, France (M.R.); Department of Radiology, Stanford University School of Medicine, Stanford, Calif (A.Kamaya); Department of Radiology, Naval Medical Center San Diego, San Diego, Calif (R.M.M.); Department of Radiology, Uniformed Services University of the Health Sciences, Bethesda, Md (R.M.M.); Department of Radiology, University of Texas MD Anderson Cancer Center, Houston, Tex (K.M.E.); Department of Radiology, Radiation Oncology and Nuclear Medicine, Université de Montréal, Montréal, Quebec, Canada (A.T.); and Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065 (V.C.)
| | - Mustafa R Bashir
- From the Liver Imaging Group, Department of Radiology, UC San Diego, San Diego, Calif (K.J.F., C.B.S.); Department of Radiology, Duke University Health System, Durham, NC (M.R.B.); Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Tex (D.T.F.); Department of Radiology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan (A.Kitao); Department of Radiology, Seoul National University College of Medicine, Seoul, South Korea (J.M.L.); Department of Radiology, West China Hospital, Sichuan University, Chengdu, China (H.J.); Joint Department of Medical Imaging, University of Toronto, Toronto, Ontario, Canada (A.Z.K.); Department of Radiology, Université Paris Cité, Paris, France, and Department of Radiology, Hôpital Beaujon, APHP.Nord, Clichy, France (M.R.); Department of Radiology, Stanford University School of Medicine, Stanford, Calif (A.Kamaya); Department of Radiology, Naval Medical Center San Diego, San Diego, Calif (R.M.M.); Department of Radiology, Uniformed Services University of the Health Sciences, Bethesda, Md (R.M.M.); Department of Radiology, University of Texas MD Anderson Cancer Center, Houston, Tex (K.M.E.); Department of Radiology, Radiation Oncology and Nuclear Medicine, Université de Montréal, Montréal, Quebec, Canada (A.T.); and Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065 (V.C.)
| | - David T Fetzer
- From the Liver Imaging Group, Department of Radiology, UC San Diego, San Diego, Calif (K.J.F., C.B.S.); Department of Radiology, Duke University Health System, Durham, NC (M.R.B.); Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Tex (D.T.F.); Department of Radiology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan (A.Kitao); Department of Radiology, Seoul National University College of Medicine, Seoul, South Korea (J.M.L.); Department of Radiology, West China Hospital, Sichuan University, Chengdu, China (H.J.); Joint Department of Medical Imaging, University of Toronto, Toronto, Ontario, Canada (A.Z.K.); Department of Radiology, Université Paris Cité, Paris, France, and Department of Radiology, Hôpital Beaujon, APHP.Nord, Clichy, France (M.R.); Department of Radiology, Stanford University School of Medicine, Stanford, Calif (A.Kamaya); Department of Radiology, Naval Medical Center San Diego, San Diego, Calif (R.M.M.); Department of Radiology, Uniformed Services University of the Health Sciences, Bethesda, Md (R.M.M.); Department of Radiology, University of Texas MD Anderson Cancer Center, Houston, Tex (K.M.E.); Department of Radiology, Radiation Oncology and Nuclear Medicine, Université de Montréal, Montréal, Quebec, Canada (A.T.); and Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065 (V.C.)
| | - Azusa Kitao
- From the Liver Imaging Group, Department of Radiology, UC San Diego, San Diego, Calif (K.J.F., C.B.S.); Department of Radiology, Duke University Health System, Durham, NC (M.R.B.); Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Tex (D.T.F.); Department of Radiology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan (A.Kitao); Department of Radiology, Seoul National University College of Medicine, Seoul, South Korea (J.M.L.); Department of Radiology, West China Hospital, Sichuan University, Chengdu, China (H.J.); Joint Department of Medical Imaging, University of Toronto, Toronto, Ontario, Canada (A.Z.K.); Department of Radiology, Université Paris Cité, Paris, France, and Department of Radiology, Hôpital Beaujon, APHP.Nord, Clichy, France (M.R.); Department of Radiology, Stanford University School of Medicine, Stanford, Calif (A.Kamaya); Department of Radiology, Naval Medical Center San Diego, San Diego, Calif (R.M.M.); Department of Radiology, Uniformed Services University of the Health Sciences, Bethesda, Md (R.M.M.); Department of Radiology, University of Texas MD Anderson Cancer Center, Houston, Tex (K.M.E.); Department of Radiology, Radiation Oncology and Nuclear Medicine, Université de Montréal, Montréal, Quebec, Canada (A.T.); and Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065 (V.C.)
| | - Jeong Min Lee
- From the Liver Imaging Group, Department of Radiology, UC San Diego, San Diego, Calif (K.J.F., C.B.S.); Department of Radiology, Duke University Health System, Durham, NC (M.R.B.); Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Tex (D.T.F.); Department of Radiology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan (A.Kitao); Department of Radiology, Seoul National University College of Medicine, Seoul, South Korea (J.M.L.); Department of Radiology, West China Hospital, Sichuan University, Chengdu, China (H.J.); Joint Department of Medical Imaging, University of Toronto, Toronto, Ontario, Canada (A.Z.K.); Department of Radiology, Université Paris Cité, Paris, France, and Department of Radiology, Hôpital Beaujon, APHP.Nord, Clichy, France (M.R.); Department of Radiology, Stanford University School of Medicine, Stanford, Calif (A.Kamaya); Department of Radiology, Naval Medical Center San Diego, San Diego, Calif (R.M.M.); Department of Radiology, Uniformed Services University of the Health Sciences, Bethesda, Md (R.M.M.); Department of Radiology, University of Texas MD Anderson Cancer Center, Houston, Tex (K.M.E.); Department of Radiology, Radiation Oncology and Nuclear Medicine, Université de Montréal, Montréal, Quebec, Canada (A.T.); and Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065 (V.C.)
| | - Hanyu Jiang
- From the Liver Imaging Group, Department of Radiology, UC San Diego, San Diego, Calif (K.J.F., C.B.S.); Department of Radiology, Duke University Health System, Durham, NC (M.R.B.); Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Tex (D.T.F.); Department of Radiology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan (A.Kitao); Department of Radiology, Seoul National University College of Medicine, Seoul, South Korea (J.M.L.); Department of Radiology, West China Hospital, Sichuan University, Chengdu, China (H.J.); Joint Department of Medical Imaging, University of Toronto, Toronto, Ontario, Canada (A.Z.K.); Department of Radiology, Université Paris Cité, Paris, France, and Department of Radiology, Hôpital Beaujon, APHP.Nord, Clichy, France (M.R.); Department of Radiology, Stanford University School of Medicine, Stanford, Calif (A.Kamaya); Department of Radiology, Naval Medical Center San Diego, San Diego, Calif (R.M.M.); Department of Radiology, Uniformed Services University of the Health Sciences, Bethesda, Md (R.M.M.); Department of Radiology, University of Texas MD Anderson Cancer Center, Houston, Tex (K.M.E.); Department of Radiology, Radiation Oncology and Nuclear Medicine, Université de Montréal, Montréal, Quebec, Canada (A.T.); and Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065 (V.C.)
| | - Ania Z Kielar
- From the Liver Imaging Group, Department of Radiology, UC San Diego, San Diego, Calif (K.J.F., C.B.S.); Department of Radiology, Duke University Health System, Durham, NC (M.R.B.); Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Tex (D.T.F.); Department of Radiology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan (A.Kitao); Department of Radiology, Seoul National University College of Medicine, Seoul, South Korea (J.M.L.); Department of Radiology, West China Hospital, Sichuan University, Chengdu, China (H.J.); Joint Department of Medical Imaging, University of Toronto, Toronto, Ontario, Canada (A.Z.K.); Department of Radiology, Université Paris Cité, Paris, France, and Department of Radiology, Hôpital Beaujon, APHP.Nord, Clichy, France (M.R.); Department of Radiology, Stanford University School of Medicine, Stanford, Calif (A.Kamaya); Department of Radiology, Naval Medical Center San Diego, San Diego, Calif (R.M.M.); Department of Radiology, Uniformed Services University of the Health Sciences, Bethesda, Md (R.M.M.); Department of Radiology, University of Texas MD Anderson Cancer Center, Houston, Tex (K.M.E.); Department of Radiology, Radiation Oncology and Nuclear Medicine, Université de Montréal, Montréal, Quebec, Canada (A.T.); and Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065 (V.C.)
| | - Maxime Ronot
- From the Liver Imaging Group, Department of Radiology, UC San Diego, San Diego, Calif (K.J.F., C.B.S.); Department of Radiology, Duke University Health System, Durham, NC (M.R.B.); Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Tex (D.T.F.); Department of Radiology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan (A.Kitao); Department of Radiology, Seoul National University College of Medicine, Seoul, South Korea (J.M.L.); Department of Radiology, West China Hospital, Sichuan University, Chengdu, China (H.J.); Joint Department of Medical Imaging, University of Toronto, Toronto, Ontario, Canada (A.Z.K.); Department of Radiology, Université Paris Cité, Paris, France, and Department of Radiology, Hôpital Beaujon, APHP.Nord, Clichy, France (M.R.); Department of Radiology, Stanford University School of Medicine, Stanford, Calif (A.Kamaya); Department of Radiology, Naval Medical Center San Diego, San Diego, Calif (R.M.M.); Department of Radiology, Uniformed Services University of the Health Sciences, Bethesda, Md (R.M.M.); Department of Radiology, University of Texas MD Anderson Cancer Center, Houston, Tex (K.M.E.); Department of Radiology, Radiation Oncology and Nuclear Medicine, Université de Montréal, Montréal, Quebec, Canada (A.T.); and Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065 (V.C.)
| | - Aya Kamaya
- From the Liver Imaging Group, Department of Radiology, UC San Diego, San Diego, Calif (K.J.F., C.B.S.); Department of Radiology, Duke University Health System, Durham, NC (M.R.B.); Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Tex (D.T.F.); Department of Radiology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan (A.Kitao); Department of Radiology, Seoul National University College of Medicine, Seoul, South Korea (J.M.L.); Department of Radiology, West China Hospital, Sichuan University, Chengdu, China (H.J.); Joint Department of Medical Imaging, University of Toronto, Toronto, Ontario, Canada (A.Z.K.); Department of Radiology, Université Paris Cité, Paris, France, and Department of Radiology, Hôpital Beaujon, APHP.Nord, Clichy, France (M.R.); Department of Radiology, Stanford University School of Medicine, Stanford, Calif (A.Kamaya); Department of Radiology, Naval Medical Center San Diego, San Diego, Calif (R.M.M.); Department of Radiology, Uniformed Services University of the Health Sciences, Bethesda, Md (R.M.M.); Department of Radiology, University of Texas MD Anderson Cancer Center, Houston, Tex (K.M.E.); Department of Radiology, Radiation Oncology and Nuclear Medicine, Université de Montréal, Montréal, Quebec, Canada (A.T.); and Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065 (V.C.)
| | - Robert M Marks
- From the Liver Imaging Group, Department of Radiology, UC San Diego, San Diego, Calif (K.J.F., C.B.S.); Department of Radiology, Duke University Health System, Durham, NC (M.R.B.); Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Tex (D.T.F.); Department of Radiology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan (A.Kitao); Department of Radiology, Seoul National University College of Medicine, Seoul, South Korea (J.M.L.); Department of Radiology, West China Hospital, Sichuan University, Chengdu, China (H.J.); Joint Department of Medical Imaging, University of Toronto, Toronto, Ontario, Canada (A.Z.K.); Department of Radiology, Université Paris Cité, Paris, France, and Department of Radiology, Hôpital Beaujon, APHP.Nord, Clichy, France (M.R.); Department of Radiology, Stanford University School of Medicine, Stanford, Calif (A.Kamaya); Department of Radiology, Naval Medical Center San Diego, San Diego, Calif (R.M.M.); Department of Radiology, Uniformed Services University of the Health Sciences, Bethesda, Md (R.M.M.); Department of Radiology, University of Texas MD Anderson Cancer Center, Houston, Tex (K.M.E.); Department of Radiology, Radiation Oncology and Nuclear Medicine, Université de Montréal, Montréal, Quebec, Canada (A.T.); and Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065 (V.C.)
| | - Khaled M Elsayes
- From the Liver Imaging Group, Department of Radiology, UC San Diego, San Diego, Calif (K.J.F., C.B.S.); Department of Radiology, Duke University Health System, Durham, NC (M.R.B.); Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Tex (D.T.F.); Department of Radiology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan (A.Kitao); Department of Radiology, Seoul National University College of Medicine, Seoul, South Korea (J.M.L.); Department of Radiology, West China Hospital, Sichuan University, Chengdu, China (H.J.); Joint Department of Medical Imaging, University of Toronto, Toronto, Ontario, Canada (A.Z.K.); Department of Radiology, Université Paris Cité, Paris, France, and Department of Radiology, Hôpital Beaujon, APHP.Nord, Clichy, France (M.R.); Department of Radiology, Stanford University School of Medicine, Stanford, Calif (A.Kamaya); Department of Radiology, Naval Medical Center San Diego, San Diego, Calif (R.M.M.); Department of Radiology, Uniformed Services University of the Health Sciences, Bethesda, Md (R.M.M.); Department of Radiology, University of Texas MD Anderson Cancer Center, Houston, Tex (K.M.E.); Department of Radiology, Radiation Oncology and Nuclear Medicine, Université de Montréal, Montréal, Quebec, Canada (A.T.); and Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065 (V.C.)
| | - An Tang
- From the Liver Imaging Group, Department of Radiology, UC San Diego, San Diego, Calif (K.J.F., C.B.S.); Department of Radiology, Duke University Health System, Durham, NC (M.R.B.); Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Tex (D.T.F.); Department of Radiology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan (A.Kitao); Department of Radiology, Seoul National University College of Medicine, Seoul, South Korea (J.M.L.); Department of Radiology, West China Hospital, Sichuan University, Chengdu, China (H.J.); Joint Department of Medical Imaging, University of Toronto, Toronto, Ontario, Canada (A.Z.K.); Department of Radiology, Université Paris Cité, Paris, France, and Department of Radiology, Hôpital Beaujon, APHP.Nord, Clichy, France (M.R.); Department of Radiology, Stanford University School of Medicine, Stanford, Calif (A.Kamaya); Department of Radiology, Naval Medical Center San Diego, San Diego, Calif (R.M.M.); Department of Radiology, Uniformed Services University of the Health Sciences, Bethesda, Md (R.M.M.); Department of Radiology, University of Texas MD Anderson Cancer Center, Houston, Tex (K.M.E.); Department of Radiology, Radiation Oncology and Nuclear Medicine, Université de Montréal, Montréal, Quebec, Canada (A.T.); and Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065 (V.C.)
| | - Claude B Sirlin
- From the Liver Imaging Group, Department of Radiology, UC San Diego, San Diego, Calif (K.J.F., C.B.S.); Department of Radiology, Duke University Health System, Durham, NC (M.R.B.); Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Tex (D.T.F.); Department of Radiology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan (A.Kitao); Department of Radiology, Seoul National University College of Medicine, Seoul, South Korea (J.M.L.); Department of Radiology, West China Hospital, Sichuan University, Chengdu, China (H.J.); Joint Department of Medical Imaging, University of Toronto, Toronto, Ontario, Canada (A.Z.K.); Department of Radiology, Université Paris Cité, Paris, France, and Department of Radiology, Hôpital Beaujon, APHP.Nord, Clichy, France (M.R.); Department of Radiology, Stanford University School of Medicine, Stanford, Calif (A.Kamaya); Department of Radiology, Naval Medical Center San Diego, San Diego, Calif (R.M.M.); Department of Radiology, Uniformed Services University of the Health Sciences, Bethesda, Md (R.M.M.); Department of Radiology, University of Texas MD Anderson Cancer Center, Houston, Tex (K.M.E.); Department of Radiology, Radiation Oncology and Nuclear Medicine, Université de Montréal, Montréal, Quebec, Canada (A.T.); and Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065 (V.C.)
| | - Victoria Chernyak
- From the Liver Imaging Group, Department of Radiology, UC San Diego, San Diego, Calif (K.J.F., C.B.S.); Department of Radiology, Duke University Health System, Durham, NC (M.R.B.); Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Tex (D.T.F.); Department of Radiology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan (A.Kitao); Department of Radiology, Seoul National University College of Medicine, Seoul, South Korea (J.M.L.); Department of Radiology, West China Hospital, Sichuan University, Chengdu, China (H.J.); Joint Department of Medical Imaging, University of Toronto, Toronto, Ontario, Canada (A.Z.K.); Department of Radiology, Université Paris Cité, Paris, France, and Department of Radiology, Hôpital Beaujon, APHP.Nord, Clichy, France (M.R.); Department of Radiology, Stanford University School of Medicine, Stanford, Calif (A.Kamaya); Department of Radiology, Naval Medical Center San Diego, San Diego, Calif (R.M.M.); Department of Radiology, Uniformed Services University of the Health Sciences, Bethesda, Md (R.M.M.); Department of Radiology, University of Texas MD Anderson Cancer Center, Houston, Tex (K.M.E.); Department of Radiology, Radiation Oncology and Nuclear Medicine, Université de Montréal, Montréal, Quebec, Canada (A.T.); and Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065 (V.C.)
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Connor AA, Kodali S, Abdelrahim M, Javle MM, Brombosz EW, Ghobrial RM. Intrahepatic cholangiocarcinoma: The role of liver transplantation, adjunctive treatments, and prognostic biomarkers. Front Oncol 2022; 12:996710. [PMID: 36479082 PMCID: PMC9719919 DOI: 10.3389/fonc.2022.996710] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Accepted: 10/31/2022] [Indexed: 08/01/2023] Open
Abstract
Intrahepatic cholangiocarcinoma (iCCA) is a primary epithelial cell malignancy of the liver with rising incidence rate globally. Its insidious presentation, heterogeneous and aggressive biology, and recalcitrance to current therapies results in unacceptably high morbidity and mortality. This has spurred research efforts in the last decade to better characterize it molecularly with translation to improved diagnostic tools and treatments. Much of this has been driven by patient advocacy. This has renewed interest in orthotopic liver transplantation (LT) with adjunctive therapies for iCCA, which was historically disparaged due to poor recipient outcomes and donor organ scarcity. However, the optimal use of LT as a treatment for iCCA care remains unclear. Here, we review the epidemiology of iCCA, the history of LT as a treatment modality, alternative approaches to iCCA local control, the evidence for peri-operative systemic therapies, and the potential roles of biomarkers and targeted agents. In doing so, we hope to prioritize areas for continued research and identify areas where multidisciplinary care can improve outcomes.
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Affiliation(s)
- Ashton A. Connor
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr Transplant Center, Houston Methodist Hospital, Houston, TX, United States
- Department of Surgery, Houston Methodist Hospital, Houston, TX, United States
| | - Sudha Kodali
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr Transplant Center, Houston Methodist Hospital, Houston, TX, United States
- Department of Medicine, Weill Cornell Medical College, New York, NY, United States
| | - Maen Abdelrahim
- Department of Medicine, Weill Cornell Medical College, New York, NY, United States
- Section of Gastrointestinal Oncology, Department of Medical Oncology, Houston Methodist Cancer Center, Houston, TX, United States
- Cockrell Center Phase 1 Unit, Cockrell Center for Advanced Therapeutics, Houston Methodist Hospital, Houston, TX, United States
| | - Milind M. Javle
- Department of Gastrointestinal Medical Oncology, MD Anderson Cancer Center, Houston, TX, United States
| | | | - R. Mark Ghobrial
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr Transplant Center, Houston Methodist Hospital, Houston, TX, United States
- Department of Surgery, Houston Methodist Hospital, Houston, TX, United States
- Department of Medicine, Weill Cornell Medical College, New York, NY, United States
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17
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Endoscopic Evaluation and Management of Cholangiocarcinoma. Gastroenterol Clin North Am 2022; 51:519-535. [PMID: 36153108 DOI: 10.1016/j.gtc.2022.06.003] [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: 02/21/2023]
Abstract
Cholangiocarcinoma is a rare malignancy of the biliary tract with a relatively poor prognosis. As a gastroenterologist, our main role is to differentiate between benign and malignant biliary disease, help achieve a diagnosis, and palliate jaundice related to biliary obstruction. This article focuses on summarizing the various tools currently available for endoscopic evaluation and management of cholangiocarcinoma.
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18
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Macias RIR, Cardinale V, Kendall TJ, Avila MA, Guido M, Coulouarn C, Braconi C, Frampton AE, Bridgewater J, Overi D, Pereira SP, Rengo M, Kather JN, Lamarca A, Pedica F, Forner A, Valle JW, Gaudio E, Alvaro D, Banales JM, Carpino G. Clinical relevance of biomarkers in cholangiocarcinoma: critical revision and future directions. Gut 2022; 71:1669-1683. [PMID: 35580963 DOI: 10.1136/gutjnl-2022-327099] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2022] [Accepted: 04/22/2022] [Indexed: 02/06/2023]
Abstract
Cholangiocarcinoma (CCA) is a malignant tumour arising from the biliary system. In Europe, this tumour frequently presents as a sporadic cancer in patients without defined risk factors and is usually diagnosed at advanced stages with a consequent poor prognosis. Therefore, the identification of biomarkers represents an utmost need for patients with CCA. Numerous studies proposed a wide spectrum of biomarkers at tissue and molecular levels. With the present paper, a multidisciplinary group of experts within the European Network for the Study of Cholangiocarcinoma discusses the clinical role of tissue biomarkers and provides a selection based on their current relevance and potential applications in the framework of CCA. Recent advances are proposed by dividing biomarkers based on their potential role in diagnosis, prognosis and therapy response. Limitations of current biomarkers are also identified, together with specific promising areas (ie, artificial intelligence, patient-derived organoids, targeted therapy) where research should be focused to develop future biomarkers.
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Affiliation(s)
- Rocio I R Macias
- Experimental Hepatology and Drug Targeting (HEVEPHARM) group, University of Salamanca, IBSAL, Salamanca, Spain
- Center for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, Madrid, Spain
| | - Vincenzo Cardinale
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy
| | - Timothy J Kendall
- Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK
| | - Matias A Avila
- Center for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, Madrid, Spain
- Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain
| | - Maria Guido
- Department of Medicine - DIMED, University of Padua, Padua, Italy
| | - Cedric Coulouarn
- UMR_S 1242, COSS, Centre de Lutte contre le Cancer Eugène Marquis, INSERM University of Rennes 1, Rennes, France
| | - Chiara Braconi
- Institute of Cancer Sciences, University of Glasgow, Glasgow, UK
| | - Adam E Frampton
- Department of Clinical and Experimental Medicine, University of Surrey, Guildford, Surrey, UK
| | - John Bridgewater
- Department of Medical Oncology, UCL Cancer Institute, London, UK
| | - Diletta Overi
- Department of Anatomical, Histological, Forensic Medicine and Orthopaedic Sciences, Sapienza University of Rome, Rome, Italy
| | - Stephen P Pereira
- Institute for Liver & Digestive Health, University College London, London, UK
| | - Marco Rengo
- Department of Radiological Sciences, Oncology and Pathology, Sapienza University of Rome, Rome, Italy
| | - Jakob N Kather
- Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany
| | - Angela Lamarca
- Medical Oncology/Institute of Cancer Sciences, The Christie NHS Foundation Trust/University of Manchester, Manchester, UK
| | - Federica Pedica
- Department of Pathology, San Raffaele Scientific Institute, Milan, Italy
| | - Alejandro Forner
- Center for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, Madrid, Spain
- BCLC group, Liver Unit, Hospital Clínic Barcelona. IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Juan W Valle
- Medical Oncology/Institute of Cancer Sciences, The Christie NHS Foundation Trust/University of Manchester, Manchester, UK
| | - Eugenio Gaudio
- Department of Anatomical, Histological, Forensic Medicine and Orthopaedic Sciences, Sapienza University of Rome, Rome, Italy
| | - Domenico Alvaro
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Jesus M Banales
- Center for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, Madrid, Spain
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), Ikerbasque, San Sebastian, Spain
- Department of Biochemistry and Genetics, School of Sciences, University of Navarra, Pamplona, Spain
| | - Guido Carpino
- Department of Movement, Human and Health Sciences, University of Rome 'Foro Italico', Rome, Italy
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19
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De Muzio F, Grassi F, Dell’Aversana F, Fusco R, Danti G, Flammia F, Chiti G, Valeri T, Agostini A, Palumbo P, Bruno F, Cutolo C, Grassi R, Simonetti I, Giovagnoni A, Miele V, Barile A, Granata V. A Narrative Review on LI-RADS Algorithm in Liver Tumors: Prospects and Pitfalls. Diagnostics (Basel) 2022; 12:1655. [PMID: 35885561 PMCID: PMC9319674 DOI: 10.3390/diagnostics12071655] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Revised: 06/27/2022] [Accepted: 07/05/2022] [Indexed: 11/16/2022] Open
Abstract
Liver cancer is the sixth most detected tumor and the third leading cause of tumor death worldwide. Hepatocellular carcinoma (HCC) is the most common primary liver malignancy with specific risk factors and a targeted population. Imaging plays a major role in the management of HCC from screening to post-therapy follow-up. In order to optimize the diagnostic-therapeutic management and using a universal report, which allows more effective communication among the multidisciplinary team, several classification systems have been proposed over time, and LI-RADS is the most utilized. Currently, LI-RADS comprises four algorithms addressing screening and surveillance, diagnosis on computed tomography (CT)/magnetic resonance imaging (MRI), diagnosis on contrast-enhanced ultrasound (CEUS) and treatment response on CT/MRI. The algorithm allows guiding the radiologist through a stepwise process of assigning a category to a liver observation, recognizing both major and ancillary features. This process allows for characterizing liver lesions and assessing treatment. In this review, we highlighted both major and ancillary features that could define HCC. The distinctive dynamic vascular pattern of arterial hyperenhancement followed by washout in the portal-venous phase is the key hallmark of HCC, with a specificity value close to 100%. However, the sensitivity value of these combined criteria is inadequate. Recent evidence has proven that liver-specific contrast could be an important tool not only in increasing sensitivity but also in diagnosis as a major criterion. Although LI-RADS emerges as an essential instrument to support the management of liver tumors, still many improvements are needed to overcome the current limitations. In particular, features that may clearly distinguish HCC from cholangiocarcinoma (CCA) and combined HCC-CCA lesions and the assessment after locoregional radiation-based therapy are still fields of research.
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Affiliation(s)
- Federica De Muzio
- Department of Medicine and Health Sciences V. Tiberio, University of Molise, 86100 Campobasso, Italy;
| | - Francesca Grassi
- Division of Radiology, Università degli Studi della Campania Luigi Vanvitelli, 81100 Naples, Italy; (F.G.); (F.D.); (R.G.)
| | - Federica Dell’Aversana
- Division of Radiology, Università degli Studi della Campania Luigi Vanvitelli, 81100 Naples, Italy; (F.G.); (F.D.); (R.G.)
| | - Roberta Fusco
- Medical Oncology Division, Igea SpA, 80013 Naples, Italy
| | - Ginevra Danti
- Division of Radiology, Azienda Ospedaliera Universitaria Careggi, 50134 Florence, Italy; (G.D.); (F.F.); (G.C.); (V.M.)
- Italian Society of Medical and Interventional Radiology (SIRM), SIRM Foundation, 20122 Milan, Italy; (P.P.); (F.B.)
| | - Federica Flammia
- Division of Radiology, Azienda Ospedaliera Universitaria Careggi, 50134 Florence, Italy; (G.D.); (F.F.); (G.C.); (V.M.)
- Italian Society of Medical and Interventional Radiology (SIRM), SIRM Foundation, 20122 Milan, Italy; (P.P.); (F.B.)
| | - Giuditta Chiti
- Division of Radiology, Azienda Ospedaliera Universitaria Careggi, 50134 Florence, Italy; (G.D.); (F.F.); (G.C.); (V.M.)
- Italian Society of Medical and Interventional Radiology (SIRM), SIRM Foundation, 20122 Milan, Italy; (P.P.); (F.B.)
| | - Tommaso Valeri
- Department of Clinical Special and Dental Sciences, University Politecnica delle Marche, 60126 Ancona, Italy; (T.V.); (A.A.); (A.G.)
- Department of Radiological Sciences, University Hospital Ospedali Riuniti, Via Tronto 10/a, 60126 Torrette, Italy
| | - Andrea Agostini
- Department of Clinical Special and Dental Sciences, University Politecnica delle Marche, 60126 Ancona, Italy; (T.V.); (A.A.); (A.G.)
- Department of Radiological Sciences, University Hospital Ospedali Riuniti, Via Tronto 10/a, 60126 Torrette, Italy
| | - Pierpaolo Palumbo
- Italian Society of Medical and Interventional Radiology (SIRM), SIRM Foundation, 20122 Milan, Italy; (P.P.); (F.B.)
- Area of Cardiovascular and Interventional Imaging, Department of Diagnostic Imaging, Abruzzo Health Unit 1, 67100 L’Aquila, Italy
| | - Federico Bruno
- Italian Society of Medical and Interventional Radiology (SIRM), SIRM Foundation, 20122 Milan, Italy; (P.P.); (F.B.)
- Emergency Radiology, San Salvatore Hospital, Via Lorenzo Natali 1, 67100 L’Aquila, Italy;
| | - Carmen Cutolo
- Department of Medicine, Surgery and Dentistry, University of Salerno, 84084 Fisciano, Italy;
| | - Roberta Grassi
- Division of Radiology, Università degli Studi della Campania Luigi Vanvitelli, 81100 Naples, Italy; (F.G.); (F.D.); (R.G.)
- Italian Society of Medical and Interventional Radiology (SIRM), SIRM Foundation, 20122 Milan, Italy; (P.P.); (F.B.)
| | - Igino Simonetti
- Radiology Division, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, Via Mariano Semmola, 80131 Naples, Italy; (I.S.); (V.G.)
| | - Andrea Giovagnoni
- Department of Clinical Special and Dental Sciences, University Politecnica delle Marche, 60126 Ancona, Italy; (T.V.); (A.A.); (A.G.)
- Department of Radiological Sciences, University Hospital Ospedali Riuniti, Via Tronto 10/a, 60126 Torrette, Italy
| | - Vittorio Miele
- Division of Radiology, Azienda Ospedaliera Universitaria Careggi, 50134 Florence, Italy; (G.D.); (F.F.); (G.C.); (V.M.)
- Italian Society of Medical and Interventional Radiology (SIRM), SIRM Foundation, 20122 Milan, Italy; (P.P.); (F.B.)
| | - Antonio Barile
- Emergency Radiology, San Salvatore Hospital, Via Lorenzo Natali 1, 67100 L’Aquila, Italy;
| | - Vincenza Granata
- Radiology Division, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, Via Mariano Semmola, 80131 Naples, Italy; (I.S.); (V.G.)
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20
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Utility of mean platelet volume in differentiating intrahepatic cholangiocarcinoma from hepatocellular carcinoma. BMC Gastroenterol 2022; 22:288. [PMID: 35668355 PMCID: PMC9171941 DOI: 10.1186/s12876-022-02348-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Accepted: 05/24/2022] [Indexed: 01/03/2023] Open
Abstract
Background Intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) are the most prevalent histologic types of primary liver cancer. HCC and ICC differ in treatment and prognosis, warranting an effective differential diagnosis between them. This study aimed to explore the clinical value of mean platelet volume (MPV) to discriminate between HCC and ICC. Material/methods We performed a retrospective analysis of ICC and HCC patients who were from the Harbin Medical University Cancer Hospital, China. Logistic regression analysis was used to identify the independent factors for the differentiation of HCC and ICC. A receiver operating characteristic curve was built to evaluate the diagnostic performance of the potential model. An independent validation study was performed to validate the diagnostic ability. Results ICC patients were detected in 146 out of 348 patients in the primary cohort. MPV levels were decreased in ICC patients compared with those in HCC patients. Logistic regression analysis revealed that MPV was an independent factor in distinguishing HCC from ICC. A combination of sex, hepatitis B surface antigen, MPV, alpha-fetoprotein, and carbohydrate antigen 19–9 demonstrated a good capability to differentiate HCC from ICC. Similar results were achieved in the validation cohort. Conclusions MPV may be a new marker to help distinguish ICC from HCC. Further validation studies are required. Supplementary Information The online version contains supplementary material available at 10.1186/s12876-022-02348-0.
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Fiz F, Jayakody Arachchige VS, Gionso M, Pecorella I, Selvam A, Wheeler DR, Sollini M, Viganò L. Radiomics of Biliary Tumors: A Systematic Review of Current Evidence. Diagnostics (Basel) 2022; 12:diagnostics12040826. [PMID: 35453878 PMCID: PMC9024804 DOI: 10.3390/diagnostics12040826] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2022] [Revised: 03/19/2022] [Accepted: 03/25/2022] [Indexed: 02/06/2023] Open
Abstract
Biliary tumors are rare diseases with major clinical unmet needs. Standard imaging modalities provide neither a conclusive diagnosis nor robust biomarkers to drive treatment planning. In several neoplasms, texture analyses non-invasively unveiled tumor characteristics and aggressiveness. The present manuscript aims to summarize the available evidence about the role of radiomics in the management of biliary tumors. A systematic review was carried out through the most relevant databases. Original, English-language articles published before May 2021 were considered. Three main outcome measures were evaluated: prediction of pathology data; prediction of survival; and differential diagnosis. Twenty-seven studies, including a total of 3605 subjects, were identified. Mass-forming intrahepatic cholangiocarcinoma (ICC) was the subject of most studies (n = 21). Radiomics reliably predicted lymph node metastases (range, AUC = 0.729−0.900, accuracy = 0.69−0.83), tumor grading (AUC = 0.680−0.890, accuracy = 0.70−0.82), and survival (C-index = 0.673−0.889). Textural features allowed for the accurate differentiation of ICC from HCC, mixed HCC-ICC, and inflammatory masses (AUC > 0.800). For all endpoints (pathology/survival/diagnosis), the predictive/prognostic models combining radiomic and clinical data outperformed the standard clinical models. Some limitations must be acknowledged: all studies are retrospective; the analyzed imaging modalities and phases are heterogeneous; the adoption of signatures/scores limits the interpretability and applicability of results. In conclusion, radiomics may play a relevant role in the management of biliary tumors, from diagnosis to treatment planning. It provides new non-invasive biomarkers, which are complementary to the standard clinical biomarkers; however, further studies are needed for their implementation in clinical practice.
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Affiliation(s)
- Francesco Fiz
- Department of Nuclear Medicine, IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy; (F.F.); (M.S.)
| | - Visala S Jayakody Arachchige
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20072 Milan, Italy; (V.S.J.A.); (M.G.); (I.P.); (A.S.); (D.R.W.)
| | - Matteo Gionso
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20072 Milan, Italy; (V.S.J.A.); (M.G.); (I.P.); (A.S.); (D.R.W.)
| | - Ilaria Pecorella
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20072 Milan, Italy; (V.S.J.A.); (M.G.); (I.P.); (A.S.); (D.R.W.)
| | - Apoorva Selvam
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20072 Milan, Italy; (V.S.J.A.); (M.G.); (I.P.); (A.S.); (D.R.W.)
| | - Dakota Russell Wheeler
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20072 Milan, Italy; (V.S.J.A.); (M.G.); (I.P.); (A.S.); (D.R.W.)
| | - Martina Sollini
- Department of Nuclear Medicine, IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy; (F.F.); (M.S.)
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20072 Milan, Italy; (V.S.J.A.); (M.G.); (I.P.); (A.S.); (D.R.W.)
| | - Luca Viganò
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20072 Milan, Italy; (V.S.J.A.); (M.G.); (I.P.); (A.S.); (D.R.W.)
- Division of Hepatobiliary and General Surgery, Department of Surgery, IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy
- Correspondence: ; Tel.: +39-02-8224-7361
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22
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Terzi E, Giamperoli A, Iavarone M, Leoni S, De Bonis L, Granito A, Forgione A, Tovoli F, Piscaglia F. Prognosis of Single Early-Stage Hepatocellular Carcinoma (HCC) with CEUS Inconclusive Imaging (LI-RADS LR-3 and LR-4) Is No Better than Typical HCC (LR-5). Cancers (Basel) 2022; 14:336. [PMID: 35053498 PMCID: PMC8773738 DOI: 10.3390/cancers14020336] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Accepted: 01/05/2022] [Indexed: 02/07/2023] Open
Abstract
The American College of Radiology (ACR) released the Liver Imaging Report and Data System (LI-RADS) scheme, which categorizes hepatic nodules in risk classes from LR-1 to LR-5 (according to the degree of risk to be HCC) and LR-M (probable malignancy not specific for HCC). The aim of this study was to test whether HCC with different LR patterns on CEUS have different overall survival (OS) and recurrence-free survival (RFS). We retrospectively enrolled 167 patients with the first definitive diagnosis of single HCC (by using CT/MRI or histological techniques if CT/MRI were inconclusive) for whom CEUS examination was available. The median size of HCC lesions was 2.2 cm (range 1.0-7.2 cm). According to CEUS LI-RADS classification, 28 patients were in LR-3, 48 in LR-4, 83 in LR-5, and 8 in LR-M. Patient liver function and nodule characteristics were not statistically different between CEUS LI-RADS classes. Using univariate analysis, CEUS LI-RADS class was not found to be a predictor of survival (p = 0.347). In conclusion, HCC showing the CEUS LI-RADS classes LR-3 and LR-4 have no better clinical outcome than typical HCC. Such data support the EASL policy, aimed at conclusive diagnostic investigations of indeterminate nodules up to obtaining histological proof to avoid leaving aggressive HCC not timely treated.
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Affiliation(s)
- Eleonora Terzi
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCSS Azienda Ospedaliero Universitaria di Bologna, 40138 Bologna, Italy; (E.T.); (S.L.); (A.G.); (F.T.)
| | - Alice Giamperoli
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy; (A.G.); (L.D.B.); (A.F.)
| | - Massimo Iavarone
- A.M. & A. Migliavacca Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca’ Grande Maggiore Hospital, University of Milan, 20122 Milan, Italy;
| | - Simona Leoni
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCSS Azienda Ospedaliero Universitaria di Bologna, 40138 Bologna, Italy; (E.T.); (S.L.); (A.G.); (F.T.)
| | - Ludovico De Bonis
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy; (A.G.); (L.D.B.); (A.F.)
| | - Alessandro Granito
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCSS Azienda Ospedaliero Universitaria di Bologna, 40138 Bologna, Italy; (E.T.); (S.L.); (A.G.); (F.T.)
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy; (A.G.); (L.D.B.); (A.F.)
| | - Antonella Forgione
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy; (A.G.); (L.D.B.); (A.F.)
| | - Francesco Tovoli
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCSS Azienda Ospedaliero Universitaria di Bologna, 40138 Bologna, Italy; (E.T.); (S.L.); (A.G.); (F.T.)
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy; (A.G.); (L.D.B.); (A.F.)
| | - Fabio Piscaglia
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCSS Azienda Ospedaliero Universitaria di Bologna, 40138 Bologna, Italy; (E.T.); (S.L.); (A.G.); (F.T.)
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy; (A.G.); (L.D.B.); (A.F.)
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23
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Li H, Feng Y, Liu C, Li J, Li J, Wu H, Wang G, Li D. Importance of Normalization of Carbohydrate Antigen 19-9 in Patients With Intrahepatic Cholangiocarcinoma. Front Oncol 2021; 11:780455. [PMID: 35004301 PMCID: PMC8728073 DOI: 10.3389/fonc.2021.780455] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Accepted: 11/30/2021] [Indexed: 01/06/2023] Open
Abstract
BACKGROUND Although carbohydrate antigen 19-9 (CA19-9) is an established prognostic marker for intrahepatic cholangiocarcinoma (ICC) patients, the significance of elevated preoperative CA19-9 that normalized after resection remains unknown. This study aimed to investigate whether elevated preoperative CA19-9 that normalized after curative resection had an impact on prognosis among patients with ICC. METHODS Patients who underwent curative resection for stage I to III ICC between 2009 and 2018 were identified. Patients were categorized into three cohorts: normal preoperative CA19-9, elevated preoperative CA19-9 but normalized postoperative CA19-9, and persistently elevated postoperative CA19-9. Overall survival (OS), recurrence-free survival (RFS), and hazard function curves over time were analyzed. RESULTS A total of 511 patients (247 [48.3%] male; median age, 58 years) were included. Patients with elevated preoperative CA19-9 (n = 378) were associated with worse RFS and OS than those with normal preoperative CA19-9 (n = 152) (both p < 0.001). Patients with persistently elevated postoperative CA19-9 (n = 254) were correlated with lower RFS and OS than the combined cohorts with normal postoperative CA19-9 (n = 257) (both p < 0.001). The hazard function curves revealed that the risk of recurrence and mortality peaked earlier and higher in the elevated postoperative CA19-9 group than the other 2 groups. Multivariate analyses identified persistently elevated, rather than normalized, postoperative CA19-9 as an independent risk factor for shorter RFS and OS in ICC. CONCLUSIONS Elevated preoperative serum CA19-9 that normalizes after curative resection is not an indicator of poor prognosis in ICC. Patients with persistently elevated postoperative CA19-9 are at increased risk of recurrence and death.
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Affiliation(s)
- Hui Li
- Department of Liver Surgery & Liver Transplantation, West China Hospital, Sichuan University, Chengdu, China
- Department of Hepatobiliary Pancreatic Tumor Center, Chongqing University Cancer Hospital, Chongqing, China
| | - Yuan Feng
- Department of Liver Surgery & Liver Transplantation, West China Hospital, Sichuan University, Chengdu, China
- Department of General Surgery, Nanping District People's Hospital, Nanchong, China
| | - Chang Liu
- Department of Liver Surgery & Liver Transplantation, West China Hospital, Sichuan University, Chengdu, China
| | - Jiawang Li
- Department of Hepatobiliary Pancreatic Tumor Center, Chongqing University Cancer Hospital, Chongqing, China
| | - Jiaxin Li
- Department of Liver Surgery & Liver Transplantation, West China Hospital, Sichuan University, Chengdu, China
| | - Hong Wu
- Department of Liver Surgery & Liver Transplantation, West China Hospital, Sichuan University, Chengdu, China
| | - Genshu Wang
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Dewei Li
- Department of Hepatobiliary Pancreatic Tumor Center, Chongqing University Cancer Hospital, Chongqing, China
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Fariduddin MM, Syed W, Birjees A, Naqvi MR. Liver infarct masquerading as intrahepatic cholangiocarcinoma. Proc (Bayl Univ Med Cent) 2021; 34:693-695. [PMID: 34732990 DOI: 10.1080/08998280.2021.1930968] [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: 10/21/2022] Open
Abstract
Cholangiocarcinoma is one of the most lethal tumors because of its complex location and lack of good chemoradiotherapy options. When it is diagnosed, urgent intervention is needed, often involving radical surgical resection. It generally presents as a liver mass with biliary obstruction. We discuss the case of a young patient presenting with liver dysfunction and imaging mimicking a liver mass concerning for cholangiocarcinoma, where he actually had a liver infarct from splanchnic venous thrombosis from primary myelofibrosis.
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Affiliation(s)
- Maria Mohammed Fariduddin
- Department of Internal Medicine, State University of New York Upstate Medical University, Syracuse, New York
| | - Wajihuddin Syed
- Department of Hematology and Oncology, State University of New York Upstate Medical University, Syracuse, New York
| | - Ayesha Birjees
- Department of General Medicine, Fathima Institute of Medical Sciences, Kadapa, India
| | - Muhammad Raza Naqvi
- Department of Hematology and Oncology, State University of New York Upstate Medical University, Syracuse, New York
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Brindley PJ, Bachini M, Ilyas SI, Khan SA, Loukas A, Sirica AE, Teh BT, Wongkham S, Gores GJ. Cholangiocarcinoma. Nat Rev Dis Primers 2021; 7:65. [PMID: 34504109 PMCID: PMC9246479 DOI: 10.1038/s41572-021-00300-2] [Citation(s) in RCA: 423] [Impact Index Per Article: 105.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/03/2021] [Indexed: 02/08/2023]
Abstract
Cholangiocarcinoma (CCA) is a highly lethal adenocarcinoma of the hepatobiliary system, which can be classified as intrahepatic, perihilar and distal. Each anatomic subtype has distinct genetic aberrations, clinical presentations and therapeutic approaches. In endemic regions, liver fluke infection is associated with CCA, owing to the oncogenic effect of the associated chronic biliary tract inflammation. In other regions, CCA can be associated with chronic biliary tract inflammation owing to choledocholithiasis, cholelithiasis, or primary sclerosing cholangitis, but most CCAs have no identifiable cause. Administration of the anthelmintic drug praziquantel decreases the risk of CCA from liver flukes, but reinfection is common and future vaccination strategies may be more effective. Some patients with CCA are eligible for potentially curative surgical options, such as resection or liver transplantation. Genetic studies have provided new insights into the pathogenesis of CCA, and two aberrations that drive the pathogenesis of non-fluke-associated intrahepatic CCA, fibroblast growth factor receptor 2 fusions and isocitrate dehydrogenase gain-of-function mutations, can be therapeutically targeted. CCA is a highly desmoplastic cancer and targeting the tumour immune microenvironment might be a promising therapeutic approach. CCA remains a highly lethal disease and further scientific and clinical insights are needed to improve patient outcomes.
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Affiliation(s)
- Paul J. Brindley
- Department of Microbiology, Immunology & Tropical Medicine, and Research Center for Neglected Diseases of Poverty, School of Medicine and Health Sciences, George Washington University, Washington, DC, USA
| | | | - Sumera I. Ilyas
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Shahid A. Khan
- Liver Unit, Division of Digestive Diseases, Imperial College London, London, UK
| | - Alex Loukas
- Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland, Australia
| | - Alphonse E. Sirica
- Department of Pathology, Virginia Commonwealth University School of Medicine, Richmond, VA, USA
| | - Bin Tean Teh
- Laboratory of Cancer Epigenome, Division of Medical Sciences, National Cancer Centre, Singapore, Singapore
| | - Sopit Wongkham
- Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Gregory J. Gores
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA,
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A radiomic-based model of different contrast-enhanced CT phase for differentiate intrahepatic cholangiocarcinoma from inflammatory mass with hepatolithiasis. Abdom Radiol (NY) 2021; 46:3835-3844. [PMID: 33728532 DOI: 10.1007/s00261-021-03027-6] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Revised: 02/17/2021] [Accepted: 02/25/2021] [Indexed: 12/24/2022]
Abstract
BACKGROUND Intrahepatic cholangiocarcinoma (ICC) is hard to distinguish from inflammatory mass (IM) complicated with hepatolithiasis in clinical practice preoperatively. This study looked to develop and confirm the radiomics models to make a distinction between ICC with hepatolithiasis from IM and to compare the results of different contrast-enhanced computed tomography (CT) phase. METHODS The models were developed in a training cohort of 110 patients from January 2005 to June 2020. Radiomics features were extracted from both arterial phase and portal venous phase contrast-enhanced computed tomography (CT) scans. The radiomics scores based on radiomics features, were built by logistic regression after using the least absolute shrinkage and selection operator (LASSO) method. The rad-scores of two contrast -enhanced CT phases and clinical features were incorporated into a novel model. The performance of the models were determined by theirs discrimination, calibration, and clinical usefulness. The models were externally validated in 35 consecutive patients. RESULTS The radiomics signature comprised two features in arterial phase (training cohort, AUC = 0.809, sensitivity 0.700, specificity 0.848, and accuracy 0.774;validation cohort, AUC = 0.790, sensitivity 0.714, specificity 0.800, and accuracy 0.757) and three related features in portal venous phase (training cohort, AUC = 0.801, sensitivity 0.800, specificity 0.717, and accuracy 0.759; validation cohort, AUC = 0.830, sensitivity 0.700, specificity 0.750, and accuracy 0.775) showed significant association with ICC in both cohorts (P < 0.05).We also developed a model only based on clinical variables (training cohort, AUC = 0.778, sensitivity 0.567, specificity 0.891, and accuracy 0.729; validation cohort, AUC = 0.788, sensitivity 0.571, specificity 0.950, and accuracy 0.761). The radiomics-based model contained rad-score of two phases and two clinical factors (CEA and CA19-9) showed the best performance (training cohort, AUC = 0.864, sensitivity 0.867, specificity 0.804, and accuracy 0.836; validation cohort, AUC = 0.843, sensitivity 0.643, specificity 0.980, and accuracy 0.821). CONCLUSIONS Our radiomics-based models provided a diagnostic tool for differentiate intrahepatic cholangiocarcinoma (ICC) from inflammatory mass (IM) with hepatolithiasis both in arterial phase and portal venous phase. To go a step further, the diagnostic accuracy will improved by a clinico-radiologic model.
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Rompianesi G, Di Martino M, Gordon-Weeks A, Montalti R, Troisi R. Liquid biopsy in cholangiocarcinoma: Current status and future perspectives. World J Gastrointest Oncol 2021; 13:332-350. [PMID: 34040697 PMCID: PMC8131901 DOI: 10.4251/wjgo.v13.i5.332] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 03/02/2021] [Accepted: 03/31/2021] [Indexed: 02/06/2023] Open
Abstract
Cholangiocarcinoma (CCA) are a heterogeneous group of tumors in terms of aetiology, natural history, morphological subtypes, molecular alterations and management, but all sharing complex diagnosis, management, and poor prognosis. Several mutated genes and epigenetic changes have been detected in CCA, with the potential to identify diagnostic and prognostic biomarkers and therapeutic targets. Accessing tumoral components and genetic material is therefore crucial for the diagnosis, management and selection of targeted therapies; but sampling tumor tissue, when possible, is often risky and difficult to be repeated at different time points. Liquid biopsy (LB) represents a way to overcome these issues and comprises a diverse group of methodologies centering around detection of tumor biomarkers from fluid samples. Compared to the traditional tissue sampling methods LB is less invasive and can be serially repeated, allowing a real-time monitoring of the tumor genetic profile or the response to therapy. In this review, we analysis the current evidence on the possible roles of LB (circulating DNA, circulating RNA, exosomes, cytokines) in the diagnosis and management of patients affected by CCA.
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Affiliation(s)
- Gianluca Rompianesi
- Hepato-Bilio-Pancreatic, Minimally Invasive and Robotic Surgery Unit, Department of Clinical Medicine and Surgery, Federico II University Hospital, Napoli 80131, Italy
| | - Marcello Di Martino
- Hepato-Bilio-Pancreatic Surgery Unit, Department of General and Digestive Surgery, Hospital Universitario La Princesa, Madrid 28006, Spain
| | - Alex Gordon-Weeks
- Nuffield Department of Surgical Sciences, University of Oxford, Oxford OX3 9DU, United Kingdom
| | - Roberto Montalti
- Hepato-Bilio-Pancreatic, Minimally Invasive and Robotic Surgery Unit, Department of Clinical Medicine and Surgery, Federico II University Hospital, Napoli 80131, Italy
| | - Roberto Troisi
- Hepato-Bilio-Pancreatic, Minimally Invasive and Robotic Surgery Unit, Department of Clinical Medicine and Surgery, Federico II University Hospital, Napoli 80131, Italy
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Reig M, Forner A, Ávila MA, Ayuso C, Mínguez B, Varela M, Bilbao I, Bilbao JI, Burrel M, Bustamante J, Ferrer J, Gómez MÁ, Llovet JM, De la Mata M, Matilla A, Pardo F, Pastrana MA, Rodríguez-Perálvarez M, Tabernero J, Urbano J, Vera R, Sangro B, Bruix J. Diagnosis and treatment of hepatocellular carcinoma. Update of the consensus document of the AEEH, AEC, SEOM, SERAM, SERVEI, and SETH. Med Clin (Barc) 2021; 156:463.e1-463.e30. [PMID: 33461840 DOI: 10.1016/j.medcli.2020.09.022] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Revised: 09/12/2020] [Accepted: 09/15/2020] [Indexed: 12/12/2022]
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver neoplasm and one of the most common causes of death in patients with cirrhosis of the liver. In parallel, with recognition of the clinical relevance of this cancer, major new developments have recently appeared in its diagnosis, prognostic assessment and in particular, in its treatment. Therefore, the Spanish Association for the Study of the Liver (AEEH) has driven the need to update the clinical practice guidelines, once again inviting all the societies involved in the diagnosis and treatment of this disease to participate in the drafting and approval of the document: Spanish Society for Liver Transplantation (SETH), Spanish Society of Diagnostic Radiology (SERAM), Spanish Society of Vascular and Interventional Radiology (SERVEI), Spanish Association of Surgeons (AEC) and Spanish Society of Medical Oncology (SEOM). The clinical practice guidelines published in 2016 and accepted as National Health System Clinical Practice Guidelines were taken as the reference documents, incorporating the most important recent advances. The scientific evidence and the strength of the recommendation is based on the GRADE system.
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Affiliation(s)
- María Reig
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Hepatología, Hospital Clínic, IDIBAPS, Universidad de Barcelona, European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Barcelona, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España
| | - Alejandro Forner
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Hepatología, Hospital Clínic, IDIBAPS, Universidad de Barcelona, European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Barcelona, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España
| | - Matías A Ávila
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España; Programa de Hepatología, Centro de Investigación Médica Aplicada, Universidad de Navarra-IDISNA, Pamplona, España
| | - Carmen Ayuso
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España; Servicio de Radiodiagnóstico, Hospital Clínic Barcelona, IDIBAPS, Universidad de Barcelona, Barcelona, España
| | - Beatriz Mínguez
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España; Servicio de Hepatología, Hospital Universitario Vall d́Hebron, Grupo de Investigación en Enfermedades Hepáticas (VHIR), Vall d'Hebron Barcelona Hospital Campus, Universidad Autónoma de Barcelona. Barcelona, España
| | - María Varela
- Sección de Hepatología, Servicio de Aparato Digestivo, Hospital Universitario Central de Asturias. Oviedo, España
| | - Itxarone Bilbao
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España; Servicio de Cirugía Hepatobiliopancreática y Trasplantes Digestivos, Hospital Universitario Vall d'Hebron, Universidad Autónoma de Barcelona. Barcelona, España
| | - José Ignacio Bilbao
- Unidad de Radiología Vascular e Intervencionista, Departamento de Radiodiagnóstico, Clínica Universidad de Navarra, Pamplona, España
| | - Marta Burrel
- Servicio de Radiodiagnóstico, Hospital Clínic Barcelona, IDIBAPS, Universidad de Barcelona, Barcelona, España
| | - Javier Bustamante
- Servicio de Gastroenterología y Hepatología, Sección de Hepatología y Trasplante, Hospital Universitario de Cruces, Baracaldo, España
| | - Joana Ferrer
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Cirugía Hepatobiliopancreática, Hospital Clínic, IDIBAPS, Universidad de Barcelona, Barcelona, España
| | - Miguel Ángel Gómez
- Unidad de Cirugía Hepatobiliopancreática y Trasplantes, Hospital Universitario Virgen del Rocío, Sevilla, España
| | - Josep María Llovet
- Grupo de Investigación Traslacional en Oncología Hepática, Servicio de Hepatología, Hospital Clínic, IDIBAPS, Universidad de Barcelona, Barcelona, España
| | - Manuel De la Mata
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España; Unidad Clínica de Aparato Digestivo, Hospital Universitario Reina Sofía, Córdoba, España
| | - Ana Matilla
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España; Sección de Hepatología, Servicio de Aparato Digestivo, Hospital General Universitario Gregorio Marañón, Madrid, España
| | - Fernando Pardo
- Servicio de Cirugía Hepatobiliopancreática y Trasplante, Clínica Universidad de Navarra, Pamplona, España
| | - Miguel A Pastrana
- Servicio de Radiodiagnóstico, Hospital Universitario Puerta de Hierro, Universidad Autónoma de Madrid, Madrid, España
| | - Manuel Rodríguez-Perálvarez
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España; Unidad Clínica de Aparato Digestivo, Hospital Universitario Reina Sofía, Córdoba, España
| | - Josep Tabernero
- Servicio de Oncología Médica, Hospital Universitario Vall d'Hebron, Universidad Autónoma de Barcelona, Barcelona, España
| | - José Urbano
- Unidad de Radiología Vascular e Intervencionista, Servicio de Radiodiagnóstico, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, Madrid, España
| | - Ruth Vera
- Servicio de Oncología Médica, Complejo hospitalario de Navarra, Navarrabiomed-IDISNA, Pamplona, España
| | - Bruno Sangro
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España; Unidad de Hepatología y Área de Oncología HBP, Clínica Universidad de Navarra-IDISNA, Pamplona, España.
| | - Jordi Bruix
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Hepatología, Hospital Clínic, IDIBAPS, Universidad de Barcelona, European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Barcelona, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España.
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Caraiani C, Boca B, Bura V, Sparchez Z, Dong Y, Dietrich C. CT/MRI LI-RADS v2018 vs. CEUS LI-RADS v2017-Can Things Be Put Together? BIOLOGY 2021; 10:412. [PMID: 34066607 PMCID: PMC8148521 DOI: 10.3390/biology10050412] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Revised: 04/17/2021] [Accepted: 04/30/2021] [Indexed: 12/27/2022]
Abstract
Different LI-RADS core documents were released for CEUS and for CT/MRI. Both documents rely on major and ancillary diagnostic criteria. The present paper offers an exhaustive comparison of the two documents focusing on the similarities, but especially on the differences, complementarity, and added value of imaging techniques in classifying liver nodules in cirrhotic livers. The major diagnostic criteria are defined, and the sensitivity and specificity of each major diagnostic criteria are presented according to the literature. The existing differences between techniques in assessing the major diagnostic features can be then exploited in order to ensure a better classification and a better clinical management of liver nodules in cirrhotic livers. Ancillary features depend on the imaging technique used, and their presence can upgrade or downgrade the LI-RADS score of an observation, but only as far as LI-RADS 4. MRI is the imaging technique that provides the greatest number of ancillary features, whereas CEUS has fewer ancillary features than other imaging techniques. In the final part of the manuscript, some recommendations are made by the authors in order to guidephysicians as to when adding another imaging technique can be helpful in managing liver nodules in cirrhotic livers.
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Affiliation(s)
- Cosmin Caraiani
- Department of Medical Imaging, “Iuliu Hațieganu” University of Medicine and Pharmacy Cluj-Napoca, 400012 Cluj-Napoca, Romania;
| | - Bianca Boca
- Department of Medical Imaging, “Iuliu Hațieganu” University of Medicine and Pharmacy Cluj-Napoca, 400012 Cluj-Napoca, Romania;
- Department of Radiology, County Clinical Emergency Hospital Cluj-Napoca, 400006 Cluj-Napoca, Romania;
- Department of Radiology, “George Emil Palade” University of Medicine, Pharmacy, Science and Technology of Târgu Mureș, 540139 Târgu Mureș, Romania
| | - Vlad Bura
- Department of Radiology, County Clinical Emergency Hospital Cluj-Napoca, 400006 Cluj-Napoca, Romania;
- Department of Radiology, Addenbrooke’s Hospital and University of Cambridge, Cambridge CB2 0QQ, UK
| | - Zeno Sparchez
- Department of Gastroenterology and Hepatology, Regional Institute of Gastroenterology and Hepatology “Prof. Dr. Octavian Fodor”, 400158 Cluj-Napoca, Romania
- 3rd Medical Department, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400162 Cluj-Napoca, Romania
| | - Yi Dong
- Ultrasound Department, Zhongshan Hospital, Fudan University, Shanghai 200032, China;
| | - Christoph Dietrich
- Department Allgemeine Innere Medizin (DAIM), Kliniken Hirslanden Beau Site, Salem und Permancence, 3013 Bern, Switzerland;
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Liver Imaging and Data System (LI-RADS) Version 2018 and Other Imaging Features in Intrahepatic Cholangiocarcinoma in Chinese Adults with vs. without Chronic Hepatitis B Viral Infection. Can J Gastroenterol Hepatol 2021; 2021:6639600. [PMID: 33748033 PMCID: PMC7952186 DOI: 10.1155/2021/6639600] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Revised: 02/08/2021] [Accepted: 02/20/2021] [Indexed: 12/14/2022] Open
Abstract
PURPOSE To describe liver imaging reporting and data system (LI-RADS) version 2018 and other MRI imaging features in intrahepatic mass-forming cholangiocarcinoma (iCCA) in Chinese adults with vs. without chronic hepatitis B viral (HBV) infection. METHODS We retrospectively enrolled 89 patients with pathologically proven iCCA after multiphase imaging performed between 2004 and 2017 at a tertiary medical center in southern China. Based on whether patients had chronic HBV, iCCA was divided into two subgroups: HBV-positive (n = 50 patients, including 9 with cirrhosis) vs. HBV-negative (n = 39 patients, including 14 with hepatolithiasis and 25 with no identifiable risk factor for iCCA; none had cirrhosis). Two independent abdominal radiologists in consensus reviewed the largest mass in each patient to assign LI-RADS v2018 features; they also scored each observation's shape and location. Imaging features were compared using chi-square or Fisher's exact tests. RESULTS Most iCCAs in HBV-positive (88% (44/50)) and HBV-negative (97% (38/39)) patients had at least one LR-M feature. Compared to iCCAs in HBV-negative patients, iCCAs in HBV-positive patients were more likely to have at least one major feature of HCC (46% (23/50) vs. 8% (3/39), P < 0.001) and more likely to be smooth (42% (21/50) vs. 10% (4/39), P = 0.001). Six of 50 (12%) iCCAs in HBV-positive patients and 1/39 (3%) iCCAs in HBV-negative patients had at least one major feature of HCC without any LR-M feature. CONCLUSIONS In this retrospective single-center study in Chinese adults, iCCAs in HBV-positive patients were more likely to resemble HCCs than iCCAs in HBV-negative patients.
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31
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Kingham TP, Aveson VG, Wei AC, Castellanos JA, Allen PJ, Nussbaum DP, Hu Y, D'Angelica MI. Surgical management of biliary malignancy. Curr Probl Surg 2021; 58:100854. [PMID: 33531120 PMCID: PMC8022290 DOI: 10.1016/j.cpsurg.2020.100854] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Accepted: 06/12/2020] [Indexed: 02/07/2023]
Affiliation(s)
| | - Victoria G Aveson
- New York Presbyterian Hospital-Weill Cornel Medical Center, New York, NY
| | - Alice C Wei
- Memorial Sloan Kettering Cancer Center, New York, NY
| | | | - Peter J Allen
- Duke Cancer Center, Chief, Division of Surgical Oncology, Duke University School of Medicine, Durham, NC
| | | | - Yinin Hu
- Division of Surgical Oncology, University of Maryland, Baltimore, MD
| | - Michael I D'Angelica
- Memorial Sloan Kettering Cancer Center, Professor of Surgery, Weill Medical College of Cornell University, New York, NY..
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32
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Italian Clinical Practice Guidelines on Cholangiocarcinoma - Part I: Classification, diagnosis and staging. Dig Liver Dis 2020; 52:1282-1293. [PMID: 32893173 DOI: 10.1016/j.dld.2020.06.045] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2020] [Revised: 06/29/2020] [Accepted: 06/30/2020] [Indexed: 12/11/2022]
Abstract
Cholangiocarcinoma (CCA) is the second most common primary liver cancer, characterized by a poor prognosis and resistance to chemotherapeutics. The progressive increase in CCA incidence and mortality registered worldwide in the last two decades and the need to clarify various aspects of clinical management have prompted the Italian Association for the Study of the Liver (AISF) to commission the drafting of dedicated guidelines in collaboration with a group of Italian scientific societies. These guidelines have been formulated in accordance with the Italian National Institute of Health indications and developed by following the GRADE method and related advancements.
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Rizzo A, Ricci AD, Tavolari S, Brandi G. Circulating Tumor DNA in Biliary Tract Cancer: Current Evidence and Future Perspectives. Cancer Genomics Proteomics 2020; 17:441-452. [PMID: 32859625 PMCID: PMC7472453 DOI: 10.21873/cgp.20203] [Citation(s) in RCA: 80] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2020] [Revised: 05/19/2020] [Accepted: 05/29/2020] [Indexed: 02/06/2023] Open
Abstract
Peripheral blood of cancer patients "physiologically" presents cells and cellular components deriving from primary or metastatic sites, including circulating tumor cells (CTCs), circulating free DNA (cfDNA) and exosomes containing proteins, lipids and nucleic acids. The term circulating tumor DNA (ctDNA) indicates the part of cfDNA which derives from primary tumors and/or metastatic sites, carrying tumor-specific genetic or epigenetic alterations. Analysis of ctDNA has enormous potential applications in all stages of cancer management, including earlier diagnosis of cancer, identification of driver alterations, monitoring of treatment response and detection of resistance mechanisms. Thus, ctDNA has the potential to profoundly change current clinical practice, by moving from tissue to peripheral blood as a source of information. Herein, we review current literature regarding the potential role for ctDNA in biliary tract cancer (BTC) patients, with a particular focus on state-of-the-art techniques and future perspectives of this highly aggressive disease.
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Affiliation(s)
- Alessandro Rizzo
- Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola-Malpighi University Hospital, Bologna, Italy
| | - Angela Dalia Ricci
- Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola-Malpighi University Hospital, Bologna, Italy
| | - Simona Tavolari
- Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola-Malpighi University Hospital, Bologna, Italy
| | - Giovanni Brandi
- Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola-Malpighi University Hospital, Bologna, Italy
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Abstract
Cholangiocarcinoma is a highly lethal biliary epithelial tumor that is rare in the general population but has increased rates in patients with primary sclerosing cholangitis (PSC). It is heterogenous, and management varies by location. No effective prevention exists, and screening is likely only feasible in PSC. Patients often present in an advanced state with jaundice, weight loss, and cholestatic liver enzymes. Diagnosis requires imaging with magnetic resonance cholangiopancreatography, laboratory testing, and endoscopic retrograde cholangiopancreatography. Potentially curative options include resection and liver transplant with neoadjuvant or adjuvant chemoradiation. Chemotherapy, radiation, and locoregional therapy provide some survival benefit in unresectable disease.
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Affiliation(s)
- Adam P Buckholz
- Division of Gastroenterology and Hepatology, NewYork-Presbyterian/Weill Cornell Medical College, 1305 York Avenue, 4th Floor, New York, NY 10021, USA
| | - Robert S Brown
- Division of Gastroenterology and Hepatology, NewYork-Presbyterian/Weill Cornell Medical College, 1305 York Avenue, 4th Floor, New York, NY 10021, USA.
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35
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Cheng N, Khoo N, Chung AYF, Goh BKP, Cheow PC, Chow PKH, Lee SY, Ooi LL, Jeyaraj PR, Kam JH, Koh YX, Chan CY, Teo JY. Pre-operative Imaging Characteristics in Histology-Proven Resected Intrahepatic Cholangiocarcinoma. World J Surg 2020; 44:3862-3867. [PMID: 32720003 DOI: 10.1007/s00268-020-05698-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/08/2020] [Indexed: 12/14/2022]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are the most common primary liver cancers. With the increasing incidence of ICC over the past two decades in Asia, it is essential to differentiate between HCC and ICC. However, ICC may mimic the radiological appearance of HCC on computed tomography scans (CT) and magnetic resonance imaging (MRI), leading to misdiagnosis of ICC. The objective of this study is to evaluate and describe the association of specific pre-operative imaging characteristics (arterial enhancement, portal venous washout) in patients with histologically proven resected ICC in our centre. METHODS Data on patients with histology-proven ICC and mixed hepatocellular-cholangiocarcinomas (HCC-CC) who had undergone surgical resection at Singapore General Hospital (SGH) were identified from a prospectively maintained database. Pre-operative cross-sectional imaging reports were analysed. RESULTS Ninety-one patients underwent resection between 1 January 2000 and 31 December 2016. Among those with no risk factors for HCC, a significant percentage of patients with ICC (24.3%) show imaging characteristics of both arterial phase hyperenhancement and non-peripheral venous washout. Among patients with risk factors for HCC, between 20.0 and 33.3% of patients with pure ICC fulfilled the imaging criteria for HCC, and this proportion was generally even higher in the mixed HCC-CC group. CONCLUSIONS A significant proportion of patients with pure ICC showed pre-operative imaging characteristics which fulfilled the diagnostic criteria for HCC. The differential of ICC should be borne in mind in populations where both malignancies are endemic.
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Affiliation(s)
- Nicole Cheng
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Outram Road, Singapore, 169608, Singapore.,Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Nathanelle Khoo
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Outram Road, Singapore, 169608, Singapore
| | - Alexander Y F Chung
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Outram Road, Singapore, 169608, Singapore.,Duke-NUS Medical School, National University of Singapore, Singapore, Singapore
| | - Brian K P Goh
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Outram Road, Singapore, 169608, Singapore.,Duke-NUS Medical School, National University of Singapore, Singapore, Singapore
| | - Peng Chung Cheow
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Outram Road, Singapore, 169608, Singapore.,Duke-NUS Medical School, National University of Singapore, Singapore, Singapore
| | - Pierce K H Chow
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Outram Road, Singapore, 169608, Singapore.,Duke-NUS Medical School, National University of Singapore, Singapore, Singapore
| | - Ser Yee Lee
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Outram Road, Singapore, 169608, Singapore.,Duke-NUS Medical School, National University of Singapore, Singapore, Singapore
| | - London L Ooi
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Outram Road, Singapore, 169608, Singapore.,Duke-NUS Medical School, National University of Singapore, Singapore, Singapore
| | - Prema Raj Jeyaraj
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Outram Road, Singapore, 169608, Singapore.,Duke-NUS Medical School, National University of Singapore, Singapore, Singapore
| | - Juinn Huar Kam
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Outram Road, Singapore, 169608, Singapore.,Duke-NUS Medical School, National University of Singapore, Singapore, Singapore
| | - Ye Xin Koh
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Outram Road, Singapore, 169608, Singapore
| | - Chung Yip Chan
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Outram Road, Singapore, 169608, Singapore.,Duke-NUS Medical School, National University of Singapore, Singapore, Singapore
| | - Jin Yao Teo
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Outram Road, Singapore, 169608, Singapore. .,Duke-NUS Medical School, National University of Singapore, Singapore, Singapore.
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36
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Kim JH, Joo I, Lee JM. Atypical Appearance of Hepatocellular Carcinoma and Its Mimickers: How to Solve Challenging Cases Using Gadoxetic Acid-Enhanced Liver Magnetic Resonance Imaging. Korean J Radiol 2020; 20:1019-1041. [PMID: 31270973 PMCID: PMC6609440 DOI: 10.3348/kjr.2018.0636] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2018] [Accepted: 03/17/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) can be diagnosed noninvasively with contrast-enhanced dynamic computed tomography, magnetic resonance imaging, or ultrasonography on the basis of its hallmark imaging features of arterial phase hyperenhancement and washout on portal or delayed phase images. However, approximately 40% of HCCs show atypical imaging features, posing a significant diagnostic challenge for radiologists. Another challenge for radiologists in clinical practice is the presentation of many HCC mimickers such as intrahepatic cholangiocarcinoma, combined HCC-cholangiocarcinoma, arterioportal shunt, and hemangioma in the cirrhotic liver. The differentiation of HCCs from these mimickers on preoperative imaging studies is of critical importance. Hence, we will review the typical and atypical imaging features of HCCs and the imaging features of its common mimickers. In addition, we will discuss how to solve these challenges in practice.
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Affiliation(s)
- Jae Hyun Kim
- Department of Radiology, Seoul National University Hospital, Seoul, Korea.,Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
| | - Ijin Joo
- Department of Radiology, Seoul National University Hospital, Seoul, Korea.,Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
| | - Jeong Min Lee
- Department of Radiology, Seoul National University Hospital, Seoul, Korea.,Department of Radiology, Seoul National University College of Medicine, Seoul, Korea.,Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul, Korea.
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37
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Wang DC, Jang HJ, Kim TK. Characterization of Indeterminate Liver Lesions on CT and MRI With Contrast-Enhanced Ultrasound: What Is the Evidence? AJR Am J Roentgenol 2020; 214:1295-1304. [PMID: 32182094 DOI: 10.2214/ajr.19.21498] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
OBJECTIVE. CT or MRI is most commonly used for characterizing focal hepatic lesions. However, findings on CT and MRI are occasionally indeterminate. Contrast-enhanced ultrasound (CEUS), with its unique characteristics as a purely intravascular contrast agent and real-time evaluation of enhancement, is a useful next step. The purpose of this article is to review the evidence for performing CEUS in the assessment of indeterminate hepatic lesions seen on CT and MRI. CONCLUSION. CEUS is a useful problem-solving tool in the evaluation of liver lesions that are indeterminate on CT and MRI. Uses include detection of arterial phase hyperenhancement; differentiation between hepatocellular carcinoma and intrahepatic cholangiocarcinoma; determination of benign versus malignant tumor thrombus, benign versus neoplastic cystic hepatic lesions, and hepatocellular adenoma versus focal nodular hyperplasia; and monitoring for recurrence in postablative therapies. CEUS can help establish a confident diagnosis and determine the need for further invasive diagnosis or treatment.
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Affiliation(s)
- David C Wang
- Department of Medical Imaging, Faculty of Medicine, University of Toronto, Toronto, ON, Canada
- Joint Department of Medical Imaging, University Health Network, Mount Sinai Hospital and Women's College Hospital, University of Toronto, 585 University Ave, Toronto, ON M5G 2N2, Canada
| | - Hyun-Jung Jang
- Joint Department of Medical Imaging, University Health Network, Mount Sinai Hospital and Women's College Hospital, University of Toronto, 585 University Ave, Toronto, ON M5G 2N2, Canada
| | - Tae Kyoung Kim
- Joint Department of Medical Imaging, University Health Network, Mount Sinai Hospital and Women's College Hospital, University of Toronto, 585 University Ave, Toronto, ON M5G 2N2, Canada
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38
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Viganò L, Lleo A, Muglia R, Gennaro N, Samà L, Colapietro F, Roncalli M, Aghemo A, Chiti A, Di Tommaso L, Solbiati L, Colombo M, Torzilli G. Intrahepatic cholangiocellular carcinoma with radiological enhancement patterns mimicking hepatocellular carcinoma. Updates Surg 2020; 72:413-421. [PMID: 32323164 DOI: 10.1007/s13304-020-00750-5] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Accepted: 03/18/2020] [Indexed: 02/07/2023]
Abstract
Non-invasive diagnosis of hepatocellular carcinoma (HCC) in cirrhotic patients requires demonstration of wash-in and wash-out on contrast-enhanced imaging. Recent studies have reported misclassification of mass-forming intrahepatic cholangiocarcinoma (MFCCC) as HCC. We aimed to analyze the contrast enhancement patterns of MFCCC, focusing especially on lesions mimicking HCC. We retrospectively evaluated all consecutive patients with MFCCC who underwent surgery between 2007 and 2017. Patients with mixed HCC-MFCCC were excluded. Two expert radiologists reviewed preoperative CT and MRI. Full-nodule hyperenhancement in the arterial phase in conjunction with hypoenhancement in the portal/late phase was classified as an "HCC-like pattern". Imaging of MFCCCs with an HCC-like pattern was reviewed by an additional radiologist blinded to clinical data. Ninety-two patients were analyzed. All patients were investigated with multiphase CT and 85 with MRI. Twelve tumors (13%) showed full-nodule arterial hyperenhancement. Of these, four were hypoenhancing in the portal/late phase. Overall, 4/92 (4%) MFCCCs (4/45 in patients with cirrhosis/hepatitis, 9%) showed an HCC-like pattern accounting for misclassification as HCC on imaging review. HCC-like MFCCCs accounted for 9% of single tumors ≤ 50 mm. All HCC-like MFCCCs occurred in patients with cirrhosis or hepatitis, whereas only 47% of non-HCC-like MFCCCs did so (p = 0.053). After a median follow-up of 29 months, all patients with HCC-like MFCCCs are alive and disease free (median 64 months). In conclusion, MFCCC was misdiagnosed as typical HCC in 4% of all cases and in 9% of patients with single tumors ≤ 50 mm or with cirrhosis/hepatitis. The risk of misdiagnosis should be considered prior to treatment planning.
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Affiliation(s)
- Luca Viganò
- Division of Hepatobiliary and General Surgery, Department of Surgery, Humanitas Clinical and Research Center, IRCCS, Via Manzoni 56, Rozzano, 20089, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
| | - Ana Lleo
- Division of Internal Medicine and Hepatology, Department of Internal Medicine, Humanitas Clinical and Research Center, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
| | - Riccardo Muglia
- Department of Radiology, Humanitas Clinical and Research Center, Milan, Italy
| | - Nicolò Gennaro
- Department of Radiology, Humanitas Clinical and Research Center, Milan, Italy
| | - Laura Samà
- Division of Hepatobiliary and General Surgery, Department of Surgery, Humanitas Clinical and Research Center, IRCCS, Via Manzoni 56, Rozzano, 20089, Milan, Italy
| | - Francesca Colapietro
- Division of Internal Medicine and Hepatology, Department of Internal Medicine, Humanitas Clinical and Research Center, Milan, Italy
| | - Massimo Roncalli
- Pathology Unit, Humanitas Clinical and Research Center, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
| | - Alessio Aghemo
- Division of Internal Medicine and Hepatology, Department of Internal Medicine, Humanitas Clinical and Research Center, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
| | - Arturo Chiti
- Department of Radiology, Humanitas Clinical and Research Center, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
| | - Luca Di Tommaso
- Pathology Unit, Humanitas Clinical and Research Center, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
| | - Luigi Solbiati
- Department of Radiology, Humanitas Clinical and Research Center, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
| | - Massimo Colombo
- Division of Internal Medicine and Hepatology, Department of Internal Medicine, Humanitas Clinical and Research Center, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
| | - Guido Torzilli
- Division of Hepatobiliary and General Surgery, Department of Surgery, Humanitas Clinical and Research Center, IRCCS, Via Manzoni 56, Rozzano, 20089, Milan, Italy.
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy.
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Abstract
Intrahepatic cholangiocarcinoma (ICC) arises from the epithelial cells of the intrahepatic and extrahepatic bile ducts and occurs proximal to the segmental biliary ducts. Risk factors include chronic hepatitis and cirrhosis, biliary inflammatory diseases, and hepatobiliary flukes, although in most cases, no known risk factor is identified. ICC is highly aggressive, with long-term survival only observed in patients with a complete R0 surgical resection. Technical and physiologic resectability should be considered when performing an operative plan. Nodal involvement is among the most important prognostic factors associated with survival and a porta hepatis lymphadenectomy should be performed at the time of resection. Adjuvant chemotherapy can provide a significant survival benefit for patients with more advanced or aggressive tumors. Systemic, locoregional, and targeted therapies exist for patients with unresectable or metastatic disease.
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Affiliation(s)
- Ramy El-Diwany
- Department of Surgery, Johns Hopkins University, 600 N. Wolfe St, Tower 110 Baltimore, MD 21287, USA
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State University, 320 W. 10th Avenue, M-260 Starling Loving Hall, Columbus, OH 43210, USA
| | - Aslam Ejaz
- Department of Surgery, Johns Hopkins University, 600 N. Wolfe St, Tower 110 Baltimore, MD 21287, USA.
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40
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Iavarone M, Viganò M, Piazza N, Occhipinti V, Sangiovanni A, Maggioni M, D'Ambrosio G, Forzenigo LV, Motta F, Lampertico P, Rumi MG, Colombo M. Contrast imaging techniques to diagnose hepatocellular carcinoma in cirrhotics outside regular surveillance. Ann Hepatol 2020; 18:318-324. [PMID: 31036496 DOI: 10.1016/j.aohep.2018.09.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2018] [Revised: 09/26/2018] [Accepted: 09/28/2018] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND AIM The American Association for the Study of the Liver (AASLD) recommends contrast computerized tomography (CT-scan) and magnetic resonance (MRI) to diagnose hepatocellular carcinoma (HCC) arising in cirrhotic patients under semiannual surveillance with abdominal ultrasound (US). A US guided fine needle biopsy (FNB) serves the same purpose in radiologically undiagnosed tumors and incidentally detected nodules in cirrhotics outside surveillance. In this population, we evaluated the performance of radiological diagnosis of HCC according to 2010 AASLD recommendations. MATERIALS AND METHODS All cirrhotic patients with a liver nodule incidentally detected by US were prospectively investigated with a sequential application of CT-scan/MRI examination and a FNB. RESULTS Between 2011 and 2015, 94 patients (mean age 67 years) had a liver nodule (total 120) detected by US in the context of histologically confirmed cirrhosis. Mean nodules diameter was 40 (10-160) mm, 87 (73%) <5cm. At histology, 84 (70%) nodules were HCC, 8 (7%) intrahepatic cholangiocarcinoma, 6 (5%) metastases, 2 (2%) neuroendocrine tumors and 20 (16%) benign lesions. Hyperenhancement in arterial phase followed by wash-out in venous phases on at least one radiological technique was demonstrated in 62 nodules (61 HCC, 1 high grade dysplastic nodule), with a specificity of 97% (IC95%: 85-100%), sensitivity 73% (IC95%: 62-81%) and diagnostic accuracy 80%, being 64% for ≥5cm HCC. Sensitivity of AFP >200ng/mL was 12% (IC95%: 6-23%). CONCLUSION A single contrast imaging technique showing a typical contrast pattern confidently identifies HCC also in cirrhotic patients with an incidental liver nodule, thereby reducing the need for FNB examinations.
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Affiliation(s)
- Massimo Iavarone
- C.R.C. "A.M. & A. Migliavacca Center for Liver Disease" and Division of Gastroenterology and Hepatology, University of Milan and Fondazione IRCCS Ca' Granda Maggiore Hospital, Milan, Italy.
| | - Mauro Viganò
- Hepatology Unit, Ospedale San Giuseppe, Università di Milano, Milan, Italy
| | - Nicole Piazza
- C.R.C. "A.M. & A. Migliavacca Center for Liver Disease" and Division of Gastroenterology and Hepatology, University of Milan and Fondazione IRCCS Ca' Granda Maggiore Hospital, Milan, Italy
| | | | - Angelo Sangiovanni
- C.R.C. "A.M. & A. Migliavacca Center for Liver Disease" and Division of Gastroenterology and Hepatology, University of Milan and Fondazione IRCCS Ca' Granda Maggiore Hospital, Milan, Italy
| | - Marco Maggioni
- Department of Pathology, Fondazione IRCCS Ca' Granda, Milan, Italy
| | | | | | - Fabio Motta
- Radiology Unit, Ospedale San Giuseppe, Milan, Italy
| | - Pietro Lampertico
- C.R.C. "A.M. & A. Migliavacca Center for Liver Disease" and Division of Gastroenterology and Hepatology, University of Milan and Fondazione IRCCS Ca' Granda Maggiore Hospital, Milan, Italy
| | - Maria-Grazia Rumi
- Hepatology Unit, Ospedale San Giuseppe, Università di Milano, Milan, Italy
| | - Massimo Colombo
- Center for Translational Hepatology Research, Clinical and Research Center Humanitas Hospital, Rozzano, Italy
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Abstract
Hepatocellular carcinoma (HCC), the most common form of primary liver cancer, typically develops on the background of chronic liver disease and is an aggressive disease with dismal prognosis. Studies using next-generation sequencing of multiple regions of the same tumour nodule suggest different patterns of HCC evolution and confirm the high molecular heterogeneity in a subset of patients. Different hypotheses have been proposed to explain tumour evolution, including clonal selection or neutral and punctuated acquisition of genetic alterations. In parallel, data indicate a fundamental contribution of nonmalignant cells of the tumour microenvironment to cancer clonal evolution. Delineating these dynamics is crucial to improve the treatment of patients with HCC, and particularly to help understand how HCC evolution drives resistance to systemic therapies. A number of new minimally invasive techniques, such as liquid biopsies, could help track cancer evolution in HCC. These tools might improve our understanding of how systemic therapies affect tumour clonal composition and could facilitate implementation of real-time molecular monitoring of patients with HCC.
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42
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Chen L, Zeng F, Yao L, Fang T, Liao M, Long J, Xiao L, Deng G. Nomogram based on inflammatory indices for differentiating intrahepatic cholangiocarcinoma from hepatocellular carcinoma. Cancer Med 2020; 9:1451-1461. [PMID: 31903730 PMCID: PMC7013079 DOI: 10.1002/cam4.2823] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2019] [Revised: 12/18/2019] [Accepted: 12/22/2019] [Indexed: 12/12/2022] Open
Abstract
Objective To establish nomogram based on inflammatory indices for differentiating intrahepatic cholangiocarcinoma (ICC) from hepatocellular carcinoma (HCC). Methods A cohort of 422 patients with HCC or ICC hospitalized at Xiangya Hospital between January 2014 and December 2018 was included in the study. Univariate and multivariate analysis was performed to identify the independent differential factors. Through combining these independent differential factors, a nomogram was established for differential diagnosis between ICC and HCC. The accuracy of nomogram was evaluated by using receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). The results were validated using a prospective study on 98 consecutive patients operated on from January 2019 to November 2019 at the same institution. Results Sex (OR = 9.001, 95% CI: 3.268‐24.792, P < .001), hepatitis (OR = 0.323, 95% CI: 0.121‐0.860, P = .024), alpha‐fetoprotein (AFP) (OR = 0.997, 95% CI: 0.995‐1.000, P = .046), carbohydrate antigen 19‐9 (CA199) (OR = 1.016, 95% CI: 1.007‐1.025, P < .001), and aspartate transaminase‐to‐neutrophil ratio index (ANRI) (OR = 0.904, 95% CI: 0.843‐0.969, P = .004) were the independent differential factors for ICC. Nomogram was established with well‐fitted calibration curves through incorporating these 5 factors. Comparing model 1 including gender, hepatitis, AFP, and CA199 (C index = 0.903, 95% CI: 0.849‐0.957) and model 2 enrolling AFP and CA199 (C index = 0.850, 95% CI: 0.791‐0.908), the nomogram showed a better discrimination between ICC and HCC, with a C index of 0.920 (95% CI, 0.872‐0.968). The results were consistent in the validation cohort. DCA also confirmed the conclusion. Conclusion A nomogram was established for the differential diagnosis between ICC and HCC preoperatively, and better therapeutic choice would be made if it was applied in clinical practice.
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Affiliation(s)
- Lang Chen
- Xiangya Hospital, Central South University, Changsha, China
| | - Furong Zeng
- Xiangya Hospital, Central South University, Changsha, China
| | - Lei Yao
- Xiangya Hospital, Central South University, Changsha, China
| | - Tongdi Fang
- Xiangya Hospital, Central South University, Changsha, China
| | - Mengting Liao
- Xiangya Hospital, Central South University, Changsha, China
| | - Jing Long
- Xiangya Hospital, Central South University, Changsha, China
| | - Liang Xiao
- Xiangya Hospital, Central South University, Changsha, China
| | - Guangtong Deng
- Xiangya Hospital, Central South University, Changsha, China
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Azer SA. Deep learning with convolutional neural networks for identification of liver masses and hepatocellular carcinoma: A systematic review. World J Gastrointest Oncol 2019; 11:1218-1230. [PMID: 31908726 PMCID: PMC6937442 DOI: 10.4251/wjgo.v11.i12.1218] [Citation(s) in RCA: 44] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2019] [Revised: 07/09/2019] [Accepted: 10/03/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Artificial intelligence, such as convolutional neural networks (CNNs), has been used in the interpretation of images and the diagnosis of hepatocellular cancer (HCC) and liver masses. CNN, a machine-learning algorithm similar to deep learning, has demonstrated its capability to recognise specific features that can detect pathological lesions. AIM To assess the use of CNNs in examining HCC and liver masses images in the diagnosis of cancer and evaluating the accuracy level of CNNs and their performance. METHODS The databases PubMed, EMBASE, and the Web of Science and research books were systematically searched using related keywords. Studies analysing pathological anatomy, cellular, and radiological images on HCC or liver masses using CNNs were identified according to the study protocol to detect cancer, differentiating cancer from other lesions, or staging the lesion. The data were extracted as per a predefined extraction. The accuracy level and performance of the CNNs in detecting cancer or early stages of cancer were analysed. The primary outcomes of the study were analysing the type of cancer or liver mass and identifying the type of images that showed optimum accuracy in cancer detection. RESULTS A total of 11 studies that met the selection criteria and were consistent with the aims of the study were identified. The studies demonstrated the ability to differentiate liver masses or differentiate HCC from other lesions (n = 6), HCC from cirrhosis or development of new tumours (n = 3), and HCC nuclei grading or segmentation (n = 2). The CNNs showed satisfactory levels of accuracy. The studies aimed at detecting lesions (n = 4), classification (n = 5), and segmentation (n = 2). Several methods were used to assess the accuracy of CNN models used. CONCLUSION The role of CNNs in analysing images and as tools in early detection of HCC or liver masses has been demonstrated in these studies. While a few limitations have been identified in these studies, overall there was an optimal level of accuracy of the CNNs used in segmentation and classification of liver cancers images.
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Affiliation(s)
- Samy A Azer
- Department of Medical Education, King Saud University College of Medicine, Riyadh 11461, Saudi Arabia
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44
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Di Tommaso L, Spadaccini M, Donadon M, Personeni N, Elamin A, Aghemo A, Lleo A. Role of liver biopsy in hepatocellular carcinoma. World J Gastroenterol 2019; 25:6041-6052. [PMID: 31686761 PMCID: PMC6824282 DOI: 10.3748/wjg.v25.i40.6041] [Citation(s) in RCA: 98] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2019] [Revised: 10/04/2019] [Accepted: 10/17/2019] [Indexed: 02/06/2023] Open
Abstract
The role of liver biopsy in the diagnosis of hepatocellular carcinoma (HCC) has been challenged over time by the ability of imaging techniques to characterize liver lesions in patients with known cirrhosis. In fact, in the diagnostic algorithm for this tumor, histology is currently relegated to controversial cases. Furthermore, the risk of complications, such as tumor seeding and bleeding, as well as inadequate sampling have further limited the use of liver biopsy for HCC management. However, there is growing evidence of prognostic and therapeutic information available from microscopic and molecular analysis of HCC and, as the information content of the tissue sample increases, the advantages of liver biopsy might modify the current risk/benefit ratio. We herein review the role and potentiality of liver biopsy in the diagnosis and management of HCC. As the potentiality of precision medicine comes to the management of HCC, it will be crucial to have rapid pathways to define prognosis, and even treatment, by identifying the patients who could most benefit from target-driven therapies. All of the above reasons suggest that the current role of liver biopsy in the management of HCC needs substantial reconsideration.
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Affiliation(s)
- Luca Di Tommaso
- Pathology Unit, Humanitas Clinical and Research Center IRCCS, Rozzano 20089, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele 20090, Italy
| | - Marco Spadaccini
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele 20090, Italy
| | - Matteo Donadon
- Division of Hepatobiliary and General Surgery, Department of General Surgery, Humanitas Clinical and Research Center IRCCS, Rozzano 20089, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele 20090, Italy
| | - Nicola Personeni
- Division of Medical Oncology and Hematology, Humanitas Cancer Center, Humanitas Clinical and Research Center IRCCS, Rozzano 20089, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele 20090, Italy
| | - Abubaker Elamin
- Pathology Unit, Humanitas Clinical and Research Center IRCCS, Rozzano 20089, Italy
| | - Alessio Aghemo
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, Humanitas Clinical and Research Center IRCCS, Rozzano 20089, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele 20090, Italy
| | - Ana Lleo
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, Humanitas Clinical and Research Center IRCCS, Rozzano 20089, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele 20090, Italy
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45
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Assessment of primary liver carcinomas other than hepatocellular carcinoma (HCC) with LI-RADS v2018: comparison of the LI-RADS target population to patients without LI-RADS-defined HCC risk factors. Eur Radiol 2019; 30:996-1007. [DOI: 10.1007/s00330-019-06448-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2019] [Revised: 08/12/2019] [Accepted: 09/10/2019] [Indexed: 12/20/2022]
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46
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Huguet JM, Lobo M, Labrador JM, Boix C, Albert C, Ferrer-Barceló L, Durá AB, Suárez P, Iranzo I, Gil-Raga M, Burgos CBD, Sempere J. Diagnostic-therapeutic management of bile duct cancer. World J Clin Cases 2019; 7:1732-1752. [PMID: 31417920 PMCID: PMC6692271 DOI: 10.12998/wjcc.v7.i14.1732] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Revised: 06/18/2019] [Accepted: 06/26/2019] [Indexed: 02/05/2023] Open
Abstract
Biliary tract cancer, or cholangiocarcinoma, comprises a heterogeneous group of malignant tumors that can emerge at any part of the biliary tree. This group is the second most common type of primary liver cancer. Diagnosis is usually based on symptoms, which may be heterogeneous, and nonspecific biomarkers in serum and biopsy specimens, as well as on imaging techniques. Endoscopy-based diagnosis is essential, since it enables biopsy specimens to be taken. In addition, it can help with locoregional staging of distal tumors. Endoscopic retrograde cholangiopancreatography is a key technique for the evaluation and treatment of malignant biliary tumors. Correct staging of cholangiocarcinoma is essential in order to be able to determine the degree of resectability and assess the results of treatment. The tumor is staged based on the TNM classification of the American Joint Committee on Cancer. The approach will depend on the classification of the tumor. Thus, some patients with early-stage disease could benefit from surgery; complete surgical resection is the cornerstone of cure. However, only a minority of patients are diagnosed in the early stages and are suitable candidates for resection. In the subset of patients diagnosed with locally advanced or metastatic disease, chemotherapy has been used to improve outcome and to delay tumor progression. The approach to biliary tract tumors should be multidisciplinary, involving experienced endoscopists, oncologists, radiologists, and surgeons.
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Affiliation(s)
- José María Huguet
- Digestive Disease Department, General University Hospital of Valencia, Valencia 46014, Spain
| | - Miriam Lobo
- Medical Oncology Department, General University Hospital of Valencia, Valencia 46014, Spain
| | - José Mir Labrador
- Unidad Hepática Avanzada, Servicio de Cirugía General y Digestiva, General University Hospital of Valencia, Valencia 46014, Spain
| | - Carlos Boix
- Digestive Disease Department, General University Hospital of Valencia, Valencia 46014, Spain
| | - Cecilia Albert
- Digestive Disease Department, General University Hospital of Valencia, Valencia 46014, Spain
| | - Luis Ferrer-Barceló
- Digestive Disease Department, General University Hospital of Valencia, Valencia 46014, Spain
| | - Ana B Durá
- Digestive Disease Department, General University Hospital of Valencia, Valencia 46014, Spain
| | - Patricia Suárez
- Digestive Disease Department, General University Hospital of Valencia, Valencia 46014, Spain
| | - Isabel Iranzo
- Digestive Disease Department, General University Hospital of Valencia, Valencia 46014, Spain
| | - Mireia Gil-Raga
- Medical Oncology Department, Hospital de Requena, Requena 46340, Spain
| | - Celia Baez de Burgos
- Unidad Hepática Avanzada, Servicio de Cirugía General y Digestiva, General University Hospital of Valencia, Valencia 46014, Spain
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Liu M, Liu L, Jin E. Gastric sub-epithelial tumors: identification of gastrointestinal stromal tumors using CT with a practical scoring method. Gastric Cancer 2019; 22:769-777. [PMID: 30535637 DOI: 10.1007/s10120-018-00908-6] [Citation(s) in RCA: 18] [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: 10/16/2018] [Accepted: 11/26/2018] [Indexed: 02/07/2023]
Abstract
OBJECTIVES To determine CT features that can identify gastrointestinal stromal tumors (GISTs) among gastric sub-epithelial tumors (SETs) and to explore a practical scoring method. METHODS Sixty-four patients with gastric SETs (51 GISTs and 13 non-GISTs) from hospital I were included for primary analyses, and 92 (67 GISTs and 25 non-GISTs) from hospital II constituted a validation cohort. Pre-operative CT images were reviewed for imaging features: lesion location, growth pattern, lesion margin, enhancement pattern, dynamic pattern, attenuation at each phasic images and presence of necrosis, superficial ulcer, calcification, and peri-lesion enlarged lymph node (LN). Clinical and CT features were compared between the two groups (GISTs versus non-GISTs) and a GIST-risk scoring method was developed; then, its performance for identifying GISTs was tested in the validation cohort. RESULTS Seven clinical and CT features were significantly suggestive of GISTs rather than non-GISTs: older age (> 49 years), non-cardial location, irregular margin, lower attenuation on unenhanced images (≤ 43 HU), heterogeneous enhancement, necrosis, and absence of enlarged LN (p < 0.05). At validation step, the established scoring method with cut-off score dichotomized into ≥ 4 versus < 4 for identifying GISTs revealed an AUC of 0.97 with an accuracy of 92%, a sensitivity of 100% and a negative predictive value (NPV) of 100%. CONCLUSIONS Gastric GISTs have special CT and clinical features that differ from non-GISTs. With a simple and practical scoring method based on the significant features, GISTs can be accurately differentiated from non-GISTs.
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Affiliation(s)
- Ming Liu
- Department of Radiotherapy, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Liheng Liu
- Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China.
| | - Erhu Jin
- Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
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Yang HK, Burns PN, Jang HJ, Kono Y, Khalili K, Wilson SR, Kim TK. Contrast-enhanced ultrasound approach to the diagnosis of focal liver lesions: the importance of washout. Ultrasonography 2019; 38:289-301. [PMID: 31311068 PMCID: PMC6769186 DOI: 10.14366/usg.19006] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2019] [Accepted: 03/17/2019] [Indexed: 12/12/2022] Open
Abstract
Contrast-enhanced ultrasound (CEUS) is a powerful technique for differentiating focal liver lesions (FLLs) without the risks of potential nephrotoxicity or ionizing radiation. In the diagnostic algorithm for FLLs on CEUS, washout is an important feature, as its presence is highly suggestive of malignancy and its characteristics are useful in distinguishing hepatocellular from nonhepatocellular malignancies. Interpreting washout on CEUS requires an understanding that microbubble contrast agents are strictly intravascular, unlike computed tomography or magnetic resonance imaging contrast agents. This review explains the definition and types of washout on CEUS in accordance with the 2017 version of the CEUS Liver Imaging Reporting and Data System and presents their applications to differential diagnosis with illustrative examples. Additionally, we propose potential mechanisms of rapid washout and describe the washout phenomenon in benign entities.
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Affiliation(s)
- Hyun Kyung Yang
- Joint Department of Medical Imaging, University of Toronto, Toronto, Canada
| | - Peter N Burns
- Department of Medical Biophysics, Sunnybrook Research Institute, University of Toronto, Toronto, Canada
| | - Hyun-Jung Jang
- Joint Department of Medical Imaging, University of Toronto, Toronto, Canada
| | - Yuko Kono
- Departments of Medicine and Radiology, University of California, San Diego, CA, USA
| | - Korosh Khalili
- Joint Department of Medical Imaging, University of Toronto, Toronto, Canada
| | - Stephanie R Wilson
- Diagnostic Imaging, Department of Radiology, University of Calgary, Calgary, Canada
| | - Tae Kyoung Kim
- Joint Department of Medical Imaging, University of Toronto, Toronto, Canada
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Mao Y, Zhu Y, Qiu Y, Kong W, Mao L, Zhou Q, Chen J, He J. Predicting peritumoral Glisson's sheath invasion of intrahepatic cholangiocarcinoma with preoperative CT imaging. Quant Imaging Med Surg 2019; 9:219-229. [PMID: 30976546 PMCID: PMC6414767 DOI: 10.21037/qims.2018.12.11] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2018] [Accepted: 12/04/2018] [Indexed: 01/19/2023]
Abstract
BACKGROUND To investigate the differences of clinicopathological characteristics and computed tomography (CT) features between intrahepatic cholangiocarcinomas (ICC) with and without peritumoral Glisson's sheath invasion (PGSI), and to construct a nomogram to predict PGSI of ICCs preoperatively. METHODS The clinicopathological characteristics and CT features of 84 ICCs were retrospectively analyzed and compared between ICCs with (30/84, 35.7%) and without PGSI (54/84, 64.3%). Multivariate logistic regression analysis was used to identify preoperative independent predictors of PGSI in ICCs. A nomogram was constructed to predict PGSI preoperatively. RESULTS ICCs with and without PGSI differed significantly in the presence of abdominal pain, serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels, TNM and T stages, tumor location, intratumoral calcifications, intrahepatic bile duct dilatation, intrahepatic bile duct calculus, morphologic type and dynamic enhancement pattern on CT images (all P<0.05). Abdominal pain, serum CEA level, intrahepatic bile duct dilatation, and morphologic type were independent predictors of PGSI in ICCs. A nomogram based on those predictors was constructed to predict PGSI preoperatively with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.908 (P<0.001). CONCLUSIONS Clinicopathological characteristics and CT features differed significantly between ICCs with and without PGSI. A nomogram including abdominal pain, serum CEA level, intrahepatic bile duct dilatation, and morphologic type could predict PGSI accurately.
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Affiliation(s)
- Yingfan Mao
- Department of Radiology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China
| | - Yong Zhu
- Department of Radiology, Jiangsu Province Hospital of Traditional Chinese Medicine, the Affiliated Hospital of the Nanjing University of Chinese Medicine, Nanjing 210008, China
| | - Yudong Qiu
- Department of Hepatopancreatobiliary Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China
| | - Weiwei Kong
- Department of Oncology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China
| | - Liang Mao
- Department of Hepatopancreatobiliary Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China
| | - Qun Zhou
- Department of Radiology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China
| | - Jun Chen
- Department of Pathology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China
| | - Jian He
- Department of Radiology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China
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Sagrini E, Iavarone M, Stefanini F, Tovoli F, Vavassori S, Maggioni M, Renzulli M, Salvatore V, Stefanescu H, Colombo M, Bolondi L, Piscaglia F. Imaging of combined hepatocellular-cholangiocarcinoma in cirrhosis and risk of false diagnosis of hepatocellular carcinoma. United European Gastroenterol J 2019; 7:69-77. [PMID: 30788118 PMCID: PMC6374835 DOI: 10.1177/2050640618815378] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2018] [Accepted: 10/13/2018] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Diagnosis of hepatocellular carcinoma can be achieved by imaging in cirrhotic patients. Combined hepatocellular-cholangiocarcinoma is a primary liver tumor and its imaging patterns have been poorly investigated. Misdiagnosis for either hepatocellular carcinoma or benign lesions can occur. We aimed to evaluate the enhancement pattern of combined hepatocellular-cholangiocarcinoma in cirrhosis with imaging techniques and to estimate the risk of misdiagnosis for hepatocellular carcinoma. METHODS All histology-confirmed combined hepatocellular-cholangiocarcinoma in cirrhosis seen in two Italian centers between 2003 and 2016, in which at least one imaging technique had been performed, was retrospectively collected. The enhancement pattern was analyzed for all available imaging modalities. RESULTS A total of 37 combined hepatocellular-cholangiocarcinoma nodules were identified. Contrast-enhanced ultrasound, computed tomography, and magnetic resonance imaging had been performed in 27, 34, and 17 nodules, respectively. Contrast-enhanced ultrasound was at higher risk of misdiagnosis for pure hepatocellular carcinoma than computed tomography (p = 0.005) or magnetic resonance imaging (p = 0.040). Only six of 24 combined hepatocellular-cholangiocarcinoma lesions submitted to both contrast-enhanced ultrasound and computed tomography showed coincident patterns; contrast-enhanced ultrasound correctly suggested a condition of malignancy in a higher number of cases than computed tomography (p < 0.001) and magnetic resonance imaging (p = 0.002). CONCLUSIONS Contrast-enhanced ultrasound misdiagnosed a higher number of combined hepatocellular-cholangiocarcinoma as hepatocellular carcinoma than computed tomography and magnetic resonance imaging. However, the latter techniques were able to identify features of malignancy less often.
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Affiliation(s)
- Elisabetta Sagrini
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Massimo Iavarone
- First Division of Gastroenterology, University of Milan, Milan, Italy
| | - Federico Stefanini
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Francesco Tovoli
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Sara Vavassori
- First Division of Gastroenterology, University of Milan, Milan, Italy
| | - Marco Maggioni
- First Division of Gastroenterology, University of Milan, Milan, Italy
| | - Matteo Renzulli
- Radiology Unit, S. Orsola-Malpighi Bologna Authority Hospital, Bologna, Italy
| | - Veronica Salvatore
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Horia Stefanescu
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Massimo Colombo
- First Division of Gastroenterology, University of Milan, Milan, Italy
| | - Luigi Bolondi
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Fabio Piscaglia
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
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