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Zhou RQ, Yang PJ, Liu TT, Han DD, Liu XL, Liu LG, Si S, Yang SW, Xu SS, Guo YW, Tan HD. Liver transplantation for combined hepatocellular cholangiocarcinoma: Current evidence, selection criteria, and therapeutic controversies. World J Gastrointest Surg 2025; 17:105783. [DOI: 10.4240/wjgs.v17.i5.105783] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2025] [Revised: 03/09/2025] [Accepted: 04/09/2025] [Indexed: 05/23/2025] Open
Abstract
Combined hepatocellular cholangiocarcinoma (cHCC-CCA) is a rare and aggressive primary liver malignancy characterized by features of both HCC and CCA. Preoperative diagnosis remains challenging because of overlapping imaging and histopathological features, which often lead to misclassification. Although liver resection is the primary curative therapy, the efficacy of liver transplantation (LT) remains controversial. Historically, LT has been considered contraindicated owing to the poor prognosis, high recurrence rate of cHCC-CCA, and the potential for organ wastage. Recent studies have suggested that LT may benefit carefully selected patients, particularly those with early-stage tumors or cirrhosis. However, there is no consensus on the criteria for LT in patients with cHCC-CCA. Lymphadenectomy and vascular resection strategies were discussed along with locoregional and systemic therapies. This review synthesized the current evidence on surgical strategies for cHCC-CCA, focusing on evolving LT criteria and outcomes.
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Affiliation(s)
- Rui-Quan Zhou
- Second Department of Hepatopancreatobiliary Surgery, China-Japan Friendship Hospital, Beijing 100029, China
| | - Pei-Jun Yang
- Second Department of Hepatopancreatobiliary Surgery, China-Japan Friendship Hospital, Beijing 100029, China
| | - Tian-Tong Liu
- Second Department of Hepatopancreatobiliary Surgery, China-Japan Friendship Hospital, Beijing 100029, China
| | - Dong-Dong Han
- Second Department of Hepatopancreatobiliary Surgery, China-Japan Friendship Hospital, Beijing 100029, China
| | - Xiao-Lei Liu
- Second Department of Hepatopancreatobiliary Surgery, China-Japan Friendship Hospital, Beijing 100029, China
| | - Li-Guo Liu
- Second Department of Hepatopancreatobiliary Surgery, China-Japan Friendship Hospital, Beijing 100029, China
| | - Shuang Si
- Second Department of Hepatopancreatobiliary Surgery, China-Japan Friendship Hospital, Beijing 100029, China
| | - Shi-Wei Yang
- Second Department of Hepatopancreatobiliary Surgery, China-Japan Friendship Hospital, Beijing 100029, China
| | - Shuai-Shuai Xu
- Second Department of Hepatopancreatobiliary Surgery, China-Japan Friendship Hospital, Beijing 100029, China
| | - Yi-Wen Guo
- Second Department of Hepatopancreatobiliary Surgery, China-Japan Friendship Hospital, Beijing 100029, China
| | - Hai-Dong Tan
- Second Department of Hepatopancreatobiliary Surgery, China-Japan Friendship Hospital, Beijing 100029, China
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Zhou C, Yang C, Zeng M. Is it necessary to distinguish between combined hepatocellular carcinoma-cholangiocarcinoma with less than 10% of cholangiocarcinoma components versus hepatocellular carcinoma? Hepatol Int 2024:10.1007/s12072-024-10730-1. [PMID: 39298106 DOI: 10.1007/s12072-024-10730-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2024] [Accepted: 09/06/2024] [Indexed: 09/21/2024]
Abstract
PURPOSE Whether there are differences in recurrence-free survival (RFS) prognosis between combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CCA) cases with a small proportion of CCA components and HCC cases remains unknown. We aim to investigate the differences in RFS prognosis between cHCC-CCAs with a small proportion of CCA components and HCCs. METHODS Patients with malignant liver neoplasms who underwent MRI and surgery were prospectively recruited. All cHCC-CCA patients were divided into different groups according to the ratio of CCA components. The primary end point was recurrence-free-survival. Cox regression analysis and Kaplan-Meier survival analysis was used to investigate and compare RFS prognosis. RESULTS One hundred sixty-four cHCC-CCA cases and 271 HCC cases were enrolled. There was no significant difference in RFS prognosis between cHCC-CCA cases with a CCA component of < 10% and HCC cases (log rank p = 0.169). There were no significant differences in some major HCC-favoring MR features, such as nonrim APHE (85.7% vs. 81.5%, p = 0.546), nonperipheral washout (80.0% vs. 84.1%, p = 0.534), and enhancing capsule (62.9% vs. 45.4%, p = 0.051) between them. In addition, some clinicopathological findings had no significant differences between cHCC-CCAs with a CCA component of < 10% and HCCs (all p > 0.05). CONCLUSIONS There were no significant differences in RFS prognosis, major HCC-favoring MRI features, and clinicopathological findings between cHCC-CCAs with a CCA component of < 10% and HCCs. Therefore, we suggest that cHCC-CCAs with pathological diagnosis of less than 10% of CCA components may be treated as HCCs in clinical setting.
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Affiliation(s)
- Changwu Zhou
- Department of Radiology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
| | - Chun Yang
- Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China.
| | - Mengsu Zeng
- Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China.
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Khessairi N, Mallek I, Laabidi T, Lahmar A, Bacha D, Slama SB. Synchronous presentation of hepatocellular carcinoma and intrahepatic cholangiocarcinoma: Report of an exceptional case with review of the literature. Int J Surg Case Rep 2024; 114:109140. [PMID: 38113560 PMCID: PMC10767223 DOI: 10.1016/j.ijscr.2023.109140] [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: 10/04/2023] [Revised: 12/05/2023] [Accepted: 12/06/2023] [Indexed: 12/21/2023] Open
Abstract
INTRODUCTION AND IMPORTANCE The occurrence of distinct synchronous hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (CC) is extremely rare. Less than 50 cases have been reported in the literature. The aim of our study was to describe the clinicopathological features of this association. CASE PRESENTATION A 75-year-old female patient with chronic hepatitis C cirrhosis presented with three hepatic nodules affecting segments IV, VIII and V during follow-up of her disease. Only the V-segment nodule was radiologically suspicious of malignancy (classified as LI-RADS5). These nodules were resected after discussion of the case in a multidisciplinary meeting. Histological examination showed that the nodules in segments VIII and V corresponded respectively to an HCC with immunohistochemistry showing HepPar1 (+), CK7(-) and CK19(-), and to an intrahepatic CC with immunohistochemistry showing HepPar1 (-), CK7(+) and CK19(+). The excision was radical. The post-operative course was uncomplicated. After a 6-month follow-up, the patient did not develop any locoregional recurrence or metastases. CLINICAL DISCUSSION Synchronous association of HCC and CC is very uncommon, and diagnosis is based on pathological and immunohistochemical examination. Infection with the HCV represents a major risk factor for simultaneous association. Synchronous presentation in HCV-infected individuals has been associated with a poorer prognosis compared with cases where only a single type of liver cancer is present. CONCLUSION The prognosis of this association is generally poor, notably due to the aggressive behavior of CC. Surgical resection remains the first-line treatment option, when possible, but comprehensive management of these complex cases requires a multidisciplinary approach tailored to each patient's specific circumstances.
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Affiliation(s)
- Nayssem Khessairi
- Department of Pathology, M. Slim University Hospital Center, Tunisia.
| | - Inès Mallek
- Department of Pathology, M. Slim University Hospital Center, Tunisia
| | - Taher Laabidi
- Department of Surgery, M. Slim University Hospital Center, Tunisia
| | - Ahlem Lahmar
- Department of Pathology, M. Slim University Hospital Center, Tunisia; University of Tunis El Manar, Faculty of Medicine of Tunis, Tunisia
| | - Dhouha Bacha
- Department of Pathology, M. Slim University Hospital Center, Tunisia; University of Tunis El Manar, Faculty of Medicine of Tunis, Tunisia
| | - Sana Ben Slama
- Department of Pathology, M. Slim University Hospital Center, Tunisia; University of Tunis El Manar, Faculty of Medicine of Tunis, Tunisia
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Goodwin B, Lou J, Butchy M, Wilson T, Atabek U, Spitz F, Hong Y. Hepatocellular-Cholangiocarcinoma Collision Tumors: An Update of Current Management Practices. Am Surg 2023; 89:2685-2692. [PMID: 36031932 DOI: 10.1177/00031348221124323] [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] [Indexed: 07/28/2023]
Abstract
Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is a rare form of primary hepatic collision tumor, with an incidence ranging from 0.4 to 14.2%. Given the diagnostic challenges and lack of randomized trials, standardized treatment has yet to be established. We aim to review the literature to summarize the diagnosis, molecular characteristics, current treatment modalities, and challenges for cHCC-CC. A literature review was performed using PubMed. We included studies investigating and describing cHCC-CC, focusing on surgical, medical, and radiologic treatments. Overall prognosis is poor, with a 5-year survival rate under 30%. Minor or major hepatectomy with R0 resection is the only curative treatment; however, recurrence is likely (as high as 50% within 5 years). The role of liver transplantation is also highly debated given the biliary nature of these tumors, with cHCC-CC as a relative contraindication for liver transplantation. Although gemcitabine-based treatments had higher progression-free survival over sorafenib, there is no standard chemotherapy regimen. Treatment with gemcitabine and platinum demonstrates improved disease control rates compared to gemcitabine in conjunction with 5-fluorouracil (78.4% verse 38.5% respectively). Additionally, platinum-containing chemotherapy regimens exhibit a higher overall response rate than non-platinum regimens (21.4% verse 7.0% respectively). These molecular-directed therapies have prolonged survival for HCC, but further investigation needs to be done to assess their utility in patients with cHCC-CC. cHCC-CC is a rare and complex subset of primary hepatic neoplasms with a dismal prognosis and unstandardized treatment options. Further trials need to be performed to investigate systemic chemotherapy and immunotherapy options for patients with unresectable disease.
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Affiliation(s)
- Brandon Goodwin
- Rowan University School of Osteopathic Medicine, Stratford, NJ, USA
| | | | | | - Traeden Wilson
- Cooper Medical School of Rowan University, Camden, NJ, USA
| | | | | | - Young Hong
- Cooper University Hospital, Camden, NJ, USA
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Xu RC, Wang F, Sun JL, Abuduwaili W, Zhang GC, Liu ZY, Liu TT, Dong L, Shen XZ, Zhu JM. A novel murine model of combined hepatocellular carcinoma and intrahepatic cholangiocarcinoma. J Transl Med 2022; 20:579. [PMID: 36494846 PMCID: PMC9733131 DOI: 10.1186/s12967-022-03791-z] [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: 08/16/2022] [Accepted: 11/24/2022] [Indexed: 12/13/2022] Open
Abstract
Primary liver cancer (PLC) is a common gastrointestinal malignancy worldwide. While hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are two major pathologic types of PLC, combined HCC and ICC (cHCC-ICC) is a relatively rare subtype that shares both hepatocyte and cholangiocyte differentiation. However, the molecular feature of this unique tumor remains elusive because of its low incidence and lack of a suitable animal model. Herein, we generated a novel spontaneous cHCC-ICC model using a Sleeping Beauty-dependent transposon plasmid co-expressing oncogenic Myc and AKT1 and a CRISPR-Cas9 plasmid expressing single-guide RNA targeting p53 into mouse hepatocytes via in situ electroporation. The histological and transcriptional analysis confirmed that this model exhibits cHCC-ICC features and activates pathways committing cHCC-ICC formation, such as TGF-β, WNT, and NF-κB. Using this model, we further screened and identified LAMB1, a protein involved in cell adhesion and migration, as a potential therapeutic target for cHCC-ICC. In conclusion, our work presents a novel genetic cHCC-ICC model and provides new insights into cHCC-ICC.
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Affiliation(s)
- Ru-Chen Xu
- grid.413087.90000 0004 1755 3939Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, 180 Fenglin Rd., Shanghai, 200032 China ,grid.413087.90000 0004 1755 3939Shanghai Institute of Liver Diseases, Shanghai, China
| | - Fu Wang
- grid.413087.90000 0004 1755 3939Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, 180 Fenglin Rd., Shanghai, 200032 China ,grid.413087.90000 0004 1755 3939Shanghai Institute of Liver Diseases, Shanghai, China
| | - Jia-Lei Sun
- grid.413087.90000 0004 1755 3939Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, 180 Fenglin Rd., Shanghai, 200032 China ,grid.413087.90000 0004 1755 3939Shanghai Institute of Liver Diseases, Shanghai, China
| | - Weinire Abuduwaili
- grid.413087.90000 0004 1755 3939Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, 180 Fenglin Rd., Shanghai, 200032 China ,grid.413087.90000 0004 1755 3939Shanghai Institute of Liver Diseases, Shanghai, China
| | - Guang-Cong Zhang
- grid.413087.90000 0004 1755 3939Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, 180 Fenglin Rd., Shanghai, 200032 China ,grid.413087.90000 0004 1755 3939Shanghai Institute of Liver Diseases, Shanghai, China
| | - Zhi-Yong Liu
- grid.413087.90000 0004 1755 3939Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, 180 Fenglin Rd., Shanghai, 200032 China ,grid.413087.90000 0004 1755 3939Shanghai Institute of Liver Diseases, Shanghai, China
| | - Tao-Tao Liu
- grid.413087.90000 0004 1755 3939Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, 180 Fenglin Rd., Shanghai, 200032 China ,grid.413087.90000 0004 1755 3939Shanghai Institute of Liver Diseases, Shanghai, China
| | - Ling Dong
- grid.413087.90000 0004 1755 3939Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, 180 Fenglin Rd., Shanghai, 200032 China ,grid.413087.90000 0004 1755 3939Shanghai Institute of Liver Diseases, Shanghai, China
| | - Xi-Zhong Shen
- grid.413087.90000 0004 1755 3939Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, 180 Fenglin Rd., Shanghai, 200032 China ,grid.413087.90000 0004 1755 3939Shanghai Institute of Liver Diseases, Shanghai, China ,grid.11841.3d0000 0004 0619 8943Key Laboratory of Medical Molecular Virology, Shanghai Medical College of Fudan University, Shanghai, China
| | - Ji-Min Zhu
- grid.413087.90000 0004 1755 3939Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, 180 Fenglin Rd., Shanghai, 200032 China ,grid.413087.90000 0004 1755 3939Shanghai Institute of Liver Diseases, Shanghai, China
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Lu L, Zhang C, Yu X, Zhang L, Feng Y, Wu Y, Xia J, Chen X, Zhang R, Zhang J, Jia N, Zhang S. The Value of Contrast-Enhanced Magnetic Resonance Imaging Enhancement in the Differential Diagnosis of Hepatocellular Carcinoma and Combined Hepatocellular Cholangiocarinoma. JOURNAL OF ONCOLOGY 2022; 2022:4691172. [PMID: 36157231 PMCID: PMC9499763 DOI: 10.1155/2022/4691172] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Accepted: 08/22/2022] [Indexed: 11/23/2022]
Abstract
Background The distinction between combined hepatocellular-cholangiocarcinoma (cHCC-CC) and hepatocellular carcinoma (HCC) before the operation has an important clinical significance for optimizing the treatment plan and predicting the prognosis of patients. Magnetic resonance imaging (MRI) has been widely used in the preoperative diagnosis and evaluation of primary liver malignant tumors. Purpose The aim is to study the value of preoperative clinical data and enhanced MRI in the differential diagnosis of HCC and cHCC-CC and obtain independent risk factors for predicting cHCC-CC. Study type. Retrospective. Population. The clinical and imaging data of 157 HCC and 59 cHCC-CC patients confirmed by pathology were collected. Field Strength/Sequence. 1.5T; cross-sectional T1WI (gradient double echo sequence); cross-sectional T2WI (fast spin echo sequence, fat suppression); enhancement (3D LAVA technology). Assessment. The differences between the HCC and cHCC-CC patients were compared. Statistic Tests. Using the t-test, chi-square test, and logistic regression analysis, P < 0.05 was considered statistically significant. Result 1. CHCC-CC was more likely to show multiple lesions than HCC (28.81% vs. 10.83%, P = 0.001) and more prone to microvascular invasion (MVI) (36.31% vs. 61.02%, P < 0.001). However, HCC had a higher incidence of liver cirrhosis than cHCC-CC (50.85% vs. 72.61%, P = 0.003). 2. The incidence of nonsmooth margin was higher in the cHCC-CC group (84.75% vs. 52.23%, P < 0.001). The incidence of peritumor enhancement in the arterial phase was higher in the cHCC-CC group (11.46% vs. 62.71%, P < 0.001) 3. According to the multivariate analysis, arterial peritumor enhancement (OR = 8.833,95%CI:4.033,19.346, P < 0.001) was an independent risk factor for cHCC-CC (P < 0.001)). It had high sensitivity (62.71%) and specificity (88.54%) in the diagnosis of cHCC-CC. Date Conclusions. Liver cirrhosis and the imaging findings of GD-DTPA-enhanced MRI are helpful for the differential diagnosis of HCC and cHCC-CC. In addition, the imaging sign of peritumoral enhancement in the arterial phase has high sensitivity and specificity for the diagnosis of cHCC-CC.
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Affiliation(s)
- Lun Lu
- Department of Radiology, Eastern Hepatobilliary Surgery Hospital, The Second Military Medical University, No. 225 Changhai Road Yangpu Area, Shanghai 200433, China
| | - ChenCai Zhang
- Department of Radiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Xian Yu
- Key Laboratory for Biorheological Science and Technology of Ministry of Education (Chongqing University), Chongqing University Cancer Hospital, Chongqing 400044, China
| | - Ling Zhang
- Department of Radiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - YaYuan Feng
- Department of Radiology, Eastern Hepatobilliary Surgery Hospital, The Second Military Medical University, No. 225 Changhai Road Yangpu Area, Shanghai 200433, China
| | - YuXian Wu
- Department of Radiology, Eastern Hepatobilliary Surgery Hospital, The Second Military Medical University, No. 225 Changhai Road Yangpu Area, Shanghai 200433, China
| | - JinJu Xia
- Department of Radiology, Eastern Hepatobilliary Surgery Hospital, The Second Military Medical University, No. 225 Changhai Road Yangpu Area, Shanghai 200433, China
| | - Xue Chen
- Department of Radiology, Eastern Hepatobilliary Surgery Hospital, The Second Military Medical University, No. 225 Changhai Road Yangpu Area, Shanghai 200433, China
| | - RuiPing Zhang
- Department of Radiology, Eastern Hepatobilliary Surgery Hospital, The Second Military Medical University, No. 225 Changhai Road Yangpu Area, Shanghai 200433, China
| | - Juan Zhang
- Department of Radiology, Eastern Hepatobilliary Surgery Hospital, The Second Military Medical University, No. 225 Changhai Road Yangpu Area, Shanghai 200433, China
| | - Ningyang Jia
- Department of Radiology, Eastern Hepatobilliary Surgery Hospital, The Second Military Medical University, No. 225 Changhai Road Yangpu Area, Shanghai 200433, China
| | - SiSi Zhang
- Department of Radiology, Eastern Hepatobilliary Surgery Hospital, The Second Military Medical University, No. 225 Changhai Road Yangpu Area, Shanghai 200433, China
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Gao L, Huang JY, Lu ZJ, Lu Q. Contrast-enhanced ultrasound manifestations of synchronous combined hepatocellular-cholangiocarcinoma and hepatocellular carcinoma: A case report. World J Clin Cases 2022; 10:3615-3623. [PMID: 35611203 PMCID: PMC9048564 DOI: 10.12998/wjcc.v10.i11.3615] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2021] [Revised: 02/08/2022] [Accepted: 02/23/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Synchronous combined hepatocellular-cholangiocarcinoma (CHC) and hepatocellular carcinoma (HCC) is very rare, with few literature reports and poor clinical outcomes associated with the disorder. Surgical resection is the main treatment, which makes the preoperative diagnosis very important. However, due to imaging manifestations overlapping with HCC, diagnosis of this type of synchronous cancer is challenging and it tends to be misdiagnosed as multiple HCC. Herein, we report the contrast-enhanced ultrasound (CEUS) manifestations of a case of synchronous CHC and HCC, aiming at adding to the understanding of this disease. CEUS displayed exquisite vascularity and tissue perfusion in real time with good spatial and temporal resolution and more accurately reflect tumor washin and washout times than contrast-enhanced computed tomography (CT) in this case. CASE SUMMARY The patient was a 69-year-old female with a 20-year history of chronic hepatitis B. Due to months of epigastric pain and anorexia, she reffered to our hospital for treatment. Five days before hospitalization, abdominal magnetic resonance imaging performed at another hospital detected a space-occupying lesion in the liver. After her hospitalization, laboratory tests showed elevated alpha-fetoprotein and carbohydrate antigen 19-9 level. Two suspicious liver lesions located in S4 and S6, respectively, were identified in a cirrhotic background by abdominal contrast-enhanced CT (CECT). Furthermore, the lesion in S4 and S6 were detected by CEUS and assigned to CEUS LI-RADS 5 and M categories, respectively. The patient underwent tumor radical resections. Post-operative pathology confirmed the S4 and S6 lesions to be HCC and CHC, respectively. A newly-found suspicious liver nodule with potential malignancy was detected in liver S1 by both CEUS and CECT 7 mo after operation. CONCLUSION The CEUS characteristics of CHC and HCC are different. CEUS features in combination with clinical information could help in effective diagnosis, clinical decision-making and better prognosis.
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Affiliation(s)
- Ling Gao
- Department of Ultrasound, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
- Department of Ultrasound, Chengdu BOE hospital, Chengdu 610219, Sichuan Province, China
| | - Jia-Yan Huang
- Department of Ultrasound, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Zi-Jian Lu
- Department of Pathology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Qiang Lu
- Department of Ultrasound, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
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Chen X, Sun S, Lu Y, Shi X, Wang Z, Chen X, Han G, Zhao J, Gao Y, Wang X. Promising role of liver transplantation in patients with combined hepatocellular-cholangiocarcinoma: a propensity score matching analysis. ANNALS OF TRANSLATIONAL MEDICINE 2022; 10:434. [PMID: 35571416 PMCID: PMC9096382 DOI: 10.21037/atm-21-5391] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Accepted: 01/28/2022] [Indexed: 12/12/2022]
Abstract
Background Combined hepatocellular-cholangiocarcinoma (CHC) is a rare but vital heterogeneous histological subtype of primary liver cancer (PLC) with no standardized treatment strategy. This study aimed to preliminarily investigate the role of liver transplantation (LT) in CHC and develop a novel risk scoring model (RSM) to evaluate the benefits of transplantation. Methods The study cohort was taken from the Surveillance, Epidemiology, and End Results database. The annual percent change (APC) in incidence or ratio was calculated utilizing the Joinpoint regression. Propensity score matching (PSM) was introduced to reduce the selection bias between groups. A novel RSM was developed based on the independent prognostic factors identified by the Cox regression model. The predictive performance of the RSM was compared with the Milan Criteria and the University of California, San Francisco (UCSF) Criteria, respectively. Results A total of 223 CHC patients were enrolled, and 60 (26.9%) of them received LT. The incidence-based mortality did not decrease between 2004 and 2015 (APC =1.7%, P=0.195). Although LT was considered an independent protective predictor for CHC, it showed a declining ratio from 33.3% in 2004 to 15.4% in 2015 (APC =-8.9%, P=0.012). The LT recipients had better outcomes than others who underwent hepatectomy or local destruction (P<0.05). Compared with other subtypes of PLC, the post-transplantation prognoses of CHC patients were similar to those with hepatocellular carcinoma (P>0.05) but significantly better than those with intrahepatic cholangiocarcinoma (ICC) (P<0.05). Based on the RSM (vascular invasion: 1 point; tumor size >2 cm: 1 point; multiple tumors: 2 points), patients were stratified into two prognostic subgroups: the low-risk (scoring ≤2) and the high-risk (scoring >2 or extrahepatic metastasis) groups. Patients in the low-risk group were more likely to benefit from LT. The predictive performance of the RSM outperformed the Milan and UCSF Criteria in both the training and validation sets. Conclusions Therapeutic strategies for CHC should be further improved. Patients with CHC should also be considered potential LT candidates. The novel RSM could be helpful to stratify patients and assist clinical decision-making.
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Affiliation(s)
- Xiaoyuan Chen
- School of Medicine, Southeast University, Nanjing, China.,Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.,Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, China.,NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Nanjing, China
| | - Shiquan Sun
- Department of Dermatovenereology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Yiwei Lu
- Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.,Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, China.,NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Nanjing, China
| | - Xiaoli Shi
- School of Medicine, Southeast University, Nanjing, China.,Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.,Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, China.,NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Nanjing, China
| | - Ziyi Wang
- Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.,Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, China.,NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Nanjing, China
| | - Xuejiao Chen
- Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.,Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, China.,NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Nanjing, China
| | - Guoyong Han
- Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.,Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, China.,NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Nanjing, China
| | - Jie Zhao
- Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.,Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, China.,NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Nanjing, China.,Department of General Surgery, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China
| | - Yun Gao
- Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.,Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, China.,NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Nanjing, China
| | - Xuehao Wang
- School of Medicine, Southeast University, Nanjing, China.,Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.,Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, China.,NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Nanjing, China
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Morbidity, Prognostic Factors, and Competing Risk Nomogram for Combined Hepatocellular-Cholangiocarcinoma. JOURNAL OF ONCOLOGY 2021; 2021:3002480. [PMID: 34925507 PMCID: PMC8683178 DOI: 10.1155/2021/3002480] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Revised: 10/09/2021] [Accepted: 10/21/2021] [Indexed: 12/14/2022]
Abstract
Background Combined hepatocellular-cholangiocarcinoma (CHC) is a rare and heterogeneous histological subtype of primary liver cancer, which is still poorly understood. This study aimed to describe the epidemiological and clinical features, investigate the prognostic indicators, and develop a competing risk nomogram for CHC. Methods The study cohort was taken from the Surveillance, Epidemiology, and End Results database. The annual percent change (APC) in incidence was calculated using the joinpoint regression. The nomogram was developed based on multivariate competing risk survival analyses and validated by calibration curves. Akaike information criterion, Bayesian information criterion, Harrell's C-index, and area under the receiver operating characteristic curves were obtained to compare prognostic performance. Decision curve analysis was introduced to examine the clinical value of the models. Results The overall incidence of CHC was 0.062 per 100,000 individuals in 2004 and 0.081 per 100,000 individuals in 2018, with an APC of 1.0% (P > 0.05). CHC displayed intermediate clinicopathological features of hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Race, tumor size, vascular invasion, extrahepatic invasion, distant metastasis, grade, surgery, and Metavir stage were confirmed as the independent predictors of cancer-specific survival. The constructed nomogram was well calibrated, which showed better discrimination power and higher net benefits than the current American Joint Committee on Cancer staging system. Patients with liver transplantation had better survival than those with hepatectomy, especially patients within the Milan Criteria (P=0.022 and P=0.015). There was no survival difference between liver transplantation and hepatectomy in patients beyond the Milan Criteria (P=0.340). Conclusion The morbidity of CHC remained stable between 2004 and 2018. The constructed nomogram could predict the prognosis with good performance, which was meaningful to individual treatment strategies optimization. CHC patients should also be considered as potential liver transplantation recipients, especially those within the Milan Criteria, but the finding still needs more evidence to be further confirmed.
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10
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Park JH, Chung YE, Seo N, Choi JY, Park MS, Kim MJ. Hepatobiliary phase signal intensity: A potential method of diagnosing HCC with atypical imaging features among LR-M observations. PLoS One 2021; 16:e0257308. [PMID: 34516587 PMCID: PMC8437291 DOI: 10.1371/journal.pone.0257308] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Accepted: 08/30/2021] [Indexed: 11/19/2022] Open
Abstract
Herein, we assessed whether hepatobiliary phase (HBP) signal intensity (SI) can be used to differentiate HCC and non-HCC malignancies within LR-M observations. 106 LR-M patients based on LI-RADS v2018 who underwent gadoxetate-disodium magnetic resonance imaging and surgery from January 2009 to December 2018 were included. SI of LR-M observation on HBP was analyzed by two radiologists and categorized into dark, low and iso-to-high groups. Tumor was classified as dark when more than 50% of tumor showed hypointensity compared to spleen, as low when more than 50% of tumor showed hyperintensity compared to spleen but hypointensity compared to liver parenchyma, and as iso-to-high if there was even a focal iso-intensity or hyperintensity compared to liver parenchyma. Analysis of clinicopathological factors and association between imaging and histology was performed. Out of 106 LR-M, 42 (40%) were showed dark, 61 (58%) showed low, and 3 (3%) showed iso-to-high SI in HBP. Three iso-to-high SI LR-M were HCCs (P = 0.060) and their major histologic differentiation was Edmondson grade 1 (P = 0.001). 43 out of 61 (71%) low SI LR-M were iCCA or cHCC-CCA (P = 0.002). Inter-reader agreement of HBP SI classification was excellent, with a kappa coefficient of 0.872. LR-M with iso-to-high SI in HBP is prone to being HCC while LR-M with low SI in HBP is prone to being tumor with fibrous stroma such as iCCA and cHCC-CCA. Classification of LR-M based on HBP SI may be a helpful method of differentiating HCC from non-HCC malignancies.
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Affiliation(s)
- Jae Hyon Park
- Department of Radiology, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Yong Eun Chung
- Department of Radiology, Yonsei University College of Medicine, Seoul, Republic of Korea
- * E-mail:
| | - Nieun Seo
- Department of Radiology, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jin-Young Choi
- Department of Radiology, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Mi-Suk Park
- Department of Radiology, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Myeong-Jin Kim
- Department of Radiology, Yonsei University College of Medicine, Seoul, Republic of Korea
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11
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Targetoid appearance on T2-weighted imaging and signs of tumor vascular involvement: diagnostic value for differentiating HCC from other primary liver carcinomas. Eur Radiol 2021; 31:6868-6878. [PMID: 33590319 DOI: 10.1007/s00330-021-07743-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Revised: 12/30/2020] [Accepted: 02/03/2021] [Indexed: 12/22/2022]
Abstract
OBJECTIVES To evaluate targetoid appearance on T2-weighted imaging and signs of tumor vascular involvement as potential new LI-RADS features for differentiating hepatocellular carcinoma (HCC) from other non-HCC primary liver carcinomas (PLCs). METHODS This IRB-approved, retrospective study was performed at two liver transplant centers. The final population included 375 patients with pathologically proven lesions imaged between 2007 and 2017 with contrast-enhanced CT or MRI. The cohort consisted of 165 intrahepatic cholangiocarcinomas and 74 combined hepatocellular-cholangiocarcinomas, with the addition of 136 HCCs for control. Two abdominal radiologists (R1; R2) independently reviewed the imaging studies (112 CT; 263 MRI) and recorded the presence of targetoid appearance on T2-weighted images and features of tumor vascular involvement including encasement, narrowing, tethering, occlusion, and obliteration. The sensitivity and specificity of each feature were calculated for the diagnosis of non-HCC PLCs. Cohen's kappa (k) test was used to assess inter-reader agreement. RESULTS The sensitivity of targetoid appearance on T2-weighted images for the diagnosis of non-HCC PLCs was 27.5% and 32.6% (R1 and R2) and the specificity was 98.2% and 97.3% (R1 and R2). Among the features of tumor vascular involvement, those providing the highest sensitivity for non-HCC PLCs were vascular encasement (R1: 34.3%; R2: 37.2%) and obliteration (R1: 25.5%; R2: 29.7%). The highest specificity for non-HCC PLCs was provided by tethering (R1: 100%; R2: 97.1%) and occlusion (R1: 99.3%; R2: 99.3%). The inter-reader agreement was moderate to substantial (k = 0.48-0.77). CONCLUSIONS Targetoid appearance on T2-weighted images and features of tumor vascular involvement demonstrated high specificity for non-HCC malignancy. KEY POINTS • Targetoid appearance on T2-weighted imaging and signs of tumor vascular involvement have high specificity (92-100%) for the diagnosis of non-HCC PLCs, regardless of the presence of liver risk factors. • In the subset of patients with risk factors for HCC, the sensitivity of signs of tumor vascular involvement decreases for both readers (1.7-20.3%), while the specificity increases reaching values higher than 94.2%. • The inter-reader agreement is substantial for targetoid appearance on T2-weighted images (k = 0.74) and moderate to substantial for signs of tumor vascular involvement (k = 0.48-0.77).
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12
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Azizi AA, Hadjinicolaou AV, Goncalves C, Duckworth A, Basu B. Update on the Genetics of and Systemic Therapy Options for Combined Hepatocellular Cholangiocarcinoma. Front Oncol 2020; 10:570958. [PMID: 33102226 PMCID: PMC7545907 DOI: 10.3389/fonc.2020.570958] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Accepted: 08/26/2020] [Indexed: 12/14/2022] Open
Abstract
Combined hepatocellular-cholangiocarcinoma (cHCC-ICC) is an uncommon and aggressive form of primary liver cancer. Currently, there are no international guidelines for optimal management. For localized tumors, radical resection represents the preferred treatment option, whereas for advanced tumors, systemic therapies recommended for intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) are often selected. Emerging information from comparative cohort studies, genomic and transcriptomic data sets are starting to build a case for rationalized approaches to systemic treatment in the advanced setting specific to cHCC-ICC.
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Affiliation(s)
- Alexander A Azizi
- Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom
| | - Andreas V Hadjinicolaou
- Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom
| | - Carla Goncalves
- Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom
| | - Adam Duckworth
- Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom
| | - Bristi Basu
- Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom.,Department of Oncology, University of Cambridge, Cambridge, United Kingdom
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13
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Liu X, Khalvati F, Namdar K, Fischer S, Lewis S, Taouli B, Haider MA, Jhaveri KS. Can machine learning radiomics provide pre-operative differentiation of combined hepatocellular cholangiocarcinoma from hepatocellular carcinoma and cholangiocarcinoma to inform optimal treatment planning? Eur Radiol 2020; 31:244-255. [PMID: 32749585 DOI: 10.1007/s00330-020-07119-7] [Citation(s) in RCA: 67] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Accepted: 07/29/2020] [Indexed: 12/15/2022]
Abstract
OBJECTIVE To differentiate combined hepatocellular cholangiocarcinoma (cHCC-CC) from cholangiocarcinoma (CC) and hepatocellular carcinoma (HCC) using machine learning on MRI and CT radiomics features. METHODS This retrospective study included 85 patients aged 32 to 86 years with 86 histopathology-proven liver cancers: 24 cHCC-CC, 24 CC, and 38 HCC who had MRI and CT between 2004 and 2018. Initial CT reports and morphological evaluation of MRI features were used to assess the performance of radiologists read. Following tumor segmentation, 1419 radiomics features were extracted using PyRadiomics library and reduced to 20 principle components by principal component analysis. Support vector machine classifier was utilized to evaluate MRI and CT radiomics features for the prediction of cHCC-CC vs. non-cHCC-CC and HCC vs. non-HCC. Histopathology was the reference standard for all tumors. RESULTS Radiomics MRI features demonstrated the best performance for differentiation of cHCC-CC from non-cHCC-CC with the highest AUC of 0.77 (SD 0.19) while CT was of limited value. Contrast-enhanced MRI phases and pre-contrast and portal-phase CT showed excellent performance for the differentiation of HCC from non-HCC (AUC of 0.79 (SD 0.07) to 0.81 (SD 0.13) for MRI and AUC of 0.81 (SD 0.06) and 0.71 (SD 0.15) for CT phases, respectively). The misdiagnosis of cHCC-CC as HCC or CC using radiologists read was 69% for CT and 58% for MRI. CONCLUSIONS Our results demonstrate promising predictive performance of MRI and CT radiomics features using machine learning analysis for differentiation of cHCC-CC from HCC and CC with potential implications for treatment decisions. KEY POINTS • Retrospective study demonstrated promising predictive performance of MRI radiomics features in the differentiation of cHCC-CC from HCC and CC and of CT radiomics features in the differentiation of HCC from cHCC-CC and CC. • With future validation, radiomics analysis has the potential to inform current clinical practice for the pre-operative diagnosis of cHCC-CC and to enable optimal treatment decisions regards liver resection and transplantation.
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Affiliation(s)
- Xiaoyang Liu
- Joint Department of Medical Imaging, University Health Network, University of Toronto, Toronto, Canada
| | - Farzad Khalvati
- Lunenfeld Tanenbaum Research Institute, University of Toronto, Toronto, Canada
| | - Khashayar Namdar
- Lunenfeld Tanenbaum Research Institute, University of Toronto, Toronto, Canada
| | - Sandra Fischer
- Department of Pathology, University Health Network, University of Toronto, Toronto, Canada
| | - Sara Lewis
- Department of Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Bachir Taouli
- Department of Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Masoom A Haider
- Department of Medical Imaging, Lunenfeld Tanenbaum Research Institute and Sinai Health System, University Health Network, University of Toronto, Toronto, Canada
| | - Kartik S Jhaveri
- Joint Department of Medical Imaging, University Health Network, University of Toronto, Toronto, Canada.
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14
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Kim JH, Yoon JH, Joo I, Lee JM. Evaluation of Primary Liver Cancers Using Hepatocyte-Specific Contrast-Enhanced MRI: Pitfalls and Potential Tips. J Magn Reson Imaging 2020; 53:655-675. [PMID: 32700807 DOI: 10.1002/jmri.27213] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2020] [Revised: 04/24/2020] [Accepted: 04/24/2020] [Indexed: 12/11/2022] Open
Abstract
When radiologists interpret hepatic focal lesions seen on dynamic magnetic resonance imaging (MRI) scans, it is important not only to distinguish malignant lesions from benign ones but also to distinguish nonhepatocellular carcinoma (HCC) malignancies from HCCs. In addition, most major guidelines, including those of the American Association for the Study of Liver Disease, European Association for the Study of the Liver, and Korean Liver Cancer Association and National Cancer Center, allow for the noninvasive imaging diagnosis of HCC in at-risk patients. However, ~40% of HCC cases show atypical imaging features mimicking non-HCC malignancies. Furthermore, several benign and malignant lesions, such as flash-filling hemangioma and intrahepatic mass-forming cholangiocarcinoma, frequently look like HCC. In contrast, although multiparametric MRI options, including hepatobiliary phase and diffusion-weighted imaging, provide useful information that could help address these challenges, there remain several unresolved issues with regard to the noninvasive diagnostic criteria characterizing HCC. In this article, we discuss the typical imaging features and challenging situations related to primary liver cancers in MRI, while considering how to make a correct diagnosis. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY STAGE: 3.
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Affiliation(s)
- Jae Hyun Kim
- Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea.,Department of Radiology, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jeong Hee Yoon
- Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea.,Department of Radiology, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Ijin Joo
- Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea.,Department of Radiology, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jeong Min Lee
- Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea.,Department of Radiology, Seoul National University College of Medicine, Seoul, Republic of Korea.,Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul, Republic of Korea
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15
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Liu WR, Tian MX, Tao CY, Tang Z, Zhou YF, Song SS, Jiang XF, Wang H, Zhou PY, Qu WF, Fang Y, Ding ZB, Zhou J, Fan J, Shi YH. Adjuvant Transarterial chemoembolization does not influence recurrence-free or overall survival in patients with combined hepatocellular carcinoma and Cholangiocarcinoma after curative resection: a propensity score matching analysis. BMC Cancer 2020; 20:642. [PMID: 32650743 PMCID: PMC7350756 DOI: 10.1186/s12885-020-07138-z] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2020] [Accepted: 07/02/2020] [Indexed: 02/07/2023] Open
Abstract
Background The prognosis of patients with combined hepatocellular carcinoma and intrahepatic cholangiocarcinoma (CHC) is usually poor, and effective adjuvant therapy is missing making it important to investigate whether these patients may benefit from adjuvant transarterial chemoembolization (TACE). We aimed to evaluate the efficiency of adjuvant TACE for long-term recurrence and survival after curative resection before and after propensity score matching (PSM) analysis. Methods In this retrospective study, of 230 patients who underwent resection for CHC between January 1994 and December 2014, 46 (18.0%) patients received adjuvant TACE. Univariate and multivariate regression analyses were used to identify the independent predictive factors of survival. Cox regression analyses and log-rank tests were used to compare overall survival (OS) and disease-free survival (DFS) between patients who did or did not receive adjuvant TACE. Results A total of 230 patients (mean age 52.2 ± 11.9 years; 172 men) were enrolled, and 46 (mean age 52.7 ± 11.1 years; 38 men) patients received TACE. Before PSM, in multivariate regression analysis, γ-glutamyl transpeptidase (γ-GT), tumour nodularity, macrovascular invasion (MVI), lymphoid metastasis, and extrahepatic metastasis were associated with OS. Alanine aminotransferase (ALT), MVI, lymphoid metastasis, and preventive TACE (HR: 2.763, 95% CI: 1.769–4.314, p < 0.001) were independent prognostic factors for DFS. PSM created 46 pairs of patients. Before PSM, adjuvant preventive TACE was not associated with an increased risk of OS (HR: 0.911, 95% CI: 0.545–1.520, p = 0.720) or DFS (HR: 3.345, 95% CI: 1.686–6.638, p = 0.001). After PSM, the 5-year OS and DFS rates were comparable in the TACE group and the non-TACE group (OS: 22.7% vs 14.9%, respectively, p = 0.75; DFS: 11.2% vs 14.4%, respectively, p = 0.06). Conclusions The present study identified that adjuvant preventive TACE did not influence DFS or OS after curative resection of CHC.
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Affiliation(s)
- Wei-Ren Liu
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, 180 FengLin Road, Shanghai, 200032, China
| | - Meng-Xin Tian
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, 180 FengLin Road, Shanghai, 200032, China
| | - Chen-Yang Tao
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, 180 FengLin Road, Shanghai, 200032, China
| | - Zheng Tang
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, 180 FengLin Road, Shanghai, 200032, China
| | - Yu-Fu Zhou
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, 180 FengLin Road, Shanghai, 200032, China.,Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China
| | - Shu-Shu Song
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, 180 FengLin Road, Shanghai, 200032, China.,Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China
| | - Xi-Fei Jiang
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, 180 FengLin Road, Shanghai, 200032, China.,Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China
| | - Han Wang
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, 180 FengLin Road, Shanghai, 200032, China.,Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China
| | - Pei-Yun Zhou
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, 180 FengLin Road, Shanghai, 200032, China.,Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China
| | - Wei-Feng Qu
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, 180 FengLin Road, Shanghai, 200032, China.,Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China
| | - Yuan Fang
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, 180 FengLin Road, Shanghai, 200032, China.,Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China
| | - Zhen-Bin Ding
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, 180 FengLin Road, Shanghai, 200032, China.,Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China
| | - Jian Zhou
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, 180 FengLin Road, Shanghai, 200032, China.,Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China.,Institutes of Biomedical Sciences, Fudan University, Shanghai, China.,Shanghai Key Laboratory of Organ Transplantation, Shanghai, China.,State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China
| | - Jia Fan
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, 180 FengLin Road, Shanghai, 200032, China.,Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China.,Institutes of Biomedical Sciences, Fudan University, Shanghai, China.,Shanghai Key Laboratory of Organ Transplantation, Shanghai, China.,State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China
| | - Ying-Hong Shi
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, 180 FengLin Road, Shanghai, 200032, China. .,Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China. .,Institutes of Biomedical Sciences, Fudan University, Shanghai, China. .,Shanghai Key Laboratory of Organ Transplantation, Shanghai, China.
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16
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Panayotova GG, Paterno F, Guarrera JV, Lunsford KE. Liver Transplantation for Cholangiocarcinoma: Insights into the Prognosis and the Evolving Indications. Curr Oncol Rep 2020; 22:49. [PMID: 32297105 DOI: 10.1007/s11912-020-00910-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
PURPOSE OF REVIEW Cholangiocarcinoma (CCA) is a rare malignancy of the biliary ducts that can be classified as intrahepatic, perihilar, or distal based on anatomic location. Although surgical resection can be curative, complete excision with negative margins is often difficult to achieve. In patients with unresectable disease, long-term survival is rarely seen with medical therapy alone. A multimodal treatment approach, including liver transplantation (LT) for select patients with unresectable CCA, should be considered. RECENT FINDINGS While currently only an approved indication for early, liver-limited, perihilar cholangiocarcinoma, promising results have been achieved for LT in localized intrahepatic disease. The absolute indication for transplant for intrahepatic tumors is currently the subject of multiple investigations. Continued advances in neoadjuvant/adjuvant therapy and better understanding of tumor biology may further augment the number of candidates for surgical therapies, with liver transplant acting as a promising tool to improve patient outcomes. Thorough consideration for any expansion in the indication for liver transplant in malignancy is necessary in order to balance patient outcomes with utilization of the scarce donor organ resources.
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Affiliation(s)
- Guergana G Panayotova
- Division of Transplant and Hepatobiliary Surgery, Department of Surgery, Center for Immunity and Inflammation, Rutgers New Jersey Medical School, 185 South Orange Ave, MSB G586, Newark, NJ, 07103, USA
| | - Flavio Paterno
- Division of Transplant and Hepatobiliary Surgery, Department of Surgery, Center for Immunity and Inflammation, Rutgers New Jersey Medical School, 185 South Orange Ave, MSB G586, Newark, NJ, 07103, USA
| | - James V Guarrera
- Division of Transplant and Hepatobiliary Surgery, Department of Surgery, Center for Immunity and Inflammation, Rutgers New Jersey Medical School, 185 South Orange Ave, MSB G586, Newark, NJ, 07103, USA
| | - Keri E Lunsford
- Division of Transplant and Hepatobiliary Surgery, Department of Surgery, Center for Immunity and Inflammation, Rutgers New Jersey Medical School, 185 South Orange Ave, MSB G586, Newark, NJ, 07103, USA.
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17
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Leoni S, Sansone V, De Lorenzo S, Ielasi L, Tovoli F, Renzulli M, Golfieri R, Spinelli D, Piscaglia F. Treatment of Combined Hepatocellular and Cholangiocarcinoma. Cancers (Basel) 2020; 12:794. [PMID: 32224916 PMCID: PMC7226028 DOI: 10.3390/cancers12040794] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2020] [Revised: 03/15/2020] [Accepted: 03/23/2020] [Indexed: 02/07/2023] Open
Abstract
Combined hepatocellular and cholangiocarcinoma (HCC-CC) is a rare primary liver cancer. It is constituted by neoplastic cells of both hepatocellular and cholangiocellular derivation. Different histology types of HCC-CC have been reported, hinting at heterogeneous carcinogenic pathways leading to the development of this cancer. Due to its rarity and complexity, mixed HCC-CC is a scantly investigated condition with unmet needs and unsatisfactory outcomes. Surgery remains the preferred treatment in resectable patients. The risk of recurrence, however, is high, especially in comparison with other primary liver cancers such as hepatocellular carcinoma. In unresectable or recurring patients, the therapeutic options are challenging due to the dual nature of the neoplastic cells. Consequently, the odds of survival of patients with HCC-CC remains poor. We analysed the literature systematically about the treatment of mixed HCC-CC, reviewing the main therapeutic options and their outcomes and analysing the most interesting developments in this topic with a focus on new potential therapeutic avenues.
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Affiliation(s)
- Simona Leoni
- Internal Medicine Unit, Department of Digestive Diseases, Bologna Authority Hospital S.Orsola-Malpighi, 40136 Bologna, Italy
| | - Vito Sansone
- Department of Medical and Surgical Sciences, University of Bologna, Via Massarenti 9, 40136 Bologna, Italy; (V.S.); (L.I.); (F.T.); (F.P.)
| | - Stefania De Lorenzo
- Oncology Unit, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40136 Bologna, Italy;
| | - Luca Ielasi
- Department of Medical and Surgical Sciences, University of Bologna, Via Massarenti 9, 40136 Bologna, Italy; (V.S.); (L.I.); (F.T.); (F.P.)
| | - Francesco Tovoli
- Department of Medical and Surgical Sciences, University of Bologna, Via Massarenti 9, 40136 Bologna, Italy; (V.S.); (L.I.); (F.T.); (F.P.)
| | - Matteo Renzulli
- Radiology Unit, Department of Experimental, Diagnostic and Specialty Medicine, Sant’Orsola Hospital, University of Bologna, 40136 Bologna, Italy; (M.R.); (R.G.); (D.S.)
| | - Rita Golfieri
- Radiology Unit, Department of Experimental, Diagnostic and Specialty Medicine, Sant’Orsola Hospital, University of Bologna, 40136 Bologna, Italy; (M.R.); (R.G.); (D.S.)
| | - Daniele Spinelli
- Radiology Unit, Department of Experimental, Diagnostic and Specialty Medicine, Sant’Orsola Hospital, University of Bologna, 40136 Bologna, Italy; (M.R.); (R.G.); (D.S.)
| | - Fabio Piscaglia
- Department of Medical and Surgical Sciences, University of Bologna, Via Massarenti 9, 40136 Bologna, Italy; (V.S.); (L.I.); (F.T.); (F.P.)
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18
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Gigante E, Ronot M, Bertin C, Ciolina M, Bouattour M, Dondero F, Cauchy F, Soubrane O, Vilgrain V, Paradis V. Combining imaging and tumour biopsy improves the diagnosis of combined hepatocellular-cholangiocarcinoma. Liver Int 2019; 39:2386-2396. [PMID: 31544304 DOI: 10.1111/liv.14261] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2019] [Revised: 08/08/2019] [Accepted: 09/17/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND & AIMS Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is by definition a highly heterogeneous tumour, which significantly impacts its diagnosis. The aim of the study was to evaluate the diagnostic performance of imaging using computed tomography and/or magnetic resonance (MR) and biopsy for the diagnosis of cHCC-CCA. METHODS cHCC-CCA resected between December 2006 and April 2017 with available pre-operative imaging and tumour biopsy were retrospectively included. cHCC-CCA diagnosis was based on morphological and immunophenotypical features. A total of 21 cHCC-CCA were compared to 21 intrahepatic cholangiocarcinoma (iCCA) as controls. All biopsies were reviewed. Two radiologists reviewed the cases and classified tumours into four patterns (type 1 [progressive enhancement of the entire lesion, iCCA type], type 2 [arterial enhancement with washout, HCC type], type 3 [mixed pattern with combinations of 1, 2 and 4] and type 4 [atypical pattern, areas of arterial enhancement without washout and/or hypovascular]). RESULTS The presence of a type 3 pattern at imaging had a 48% sensitivity and 81% specificity for cHCC-CCA diagnosis. The initial diagnosis performed on biopsy was cHCC-CCA in 8/21 patients (38%). After reviewing and including immunophenotypical markers, two more cases were diagnosed as cHCC-CCA (48% sensibility, 100% specificity). When either imaging or biopsy suggested the diagnosis of cHCC-CCA, the sensitivity and specificity were 60% and 82% respectively. CONCLUSIONS We showed that a two-step strategy combining imaging as the first step and biopsy as the second step improved the diagnostic performance of cHCC-CCA.
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Affiliation(s)
- Elia Gigante
- Department of Hepatology, Saint-Antoine Hospital, APHP, Paris, France
- INSERM U1149, Centre de Recherche sur l'Inflammation, Paris, France
| | - Maxime Ronot
- Department of Radiology, Beaujon Hospital, APHP, Clichy, France
| | - Caroline Bertin
- Department of Radiology, Beaujon Hospital, APHP, Clichy, France
| | - Maria Ciolina
- Department of Radiology, Beaujon Hospital, APHP, Clichy, France
| | - Mohamed Bouattour
- Department of Digestive Oncology, Beaujon Hospital, APHP, Clichy, France
| | - Federica Dondero
- Department of Hepatobiliary Surgery, Beaujon Hospital, APHP, Clichy, France
| | - François Cauchy
- INSERM U1149, Centre de Recherche sur l'Inflammation, Paris, France
- Department of Hepatobiliary Surgery, Beaujon Hospital, APHP, Clichy, France
| | - Olivier Soubrane
- Department of Hepatobiliary Surgery, Beaujon Hospital, APHP, Clichy, France
| | | | - Valérie Paradis
- INSERM U1149, Centre de Recherche sur l'Inflammation, Paris, France
- Department of Pathology, Beaujon Hospital, APHP, Clichy, France
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Chuang YH, Ou HY, Yu CY, Chen CL, Weng CC, Tsang LLC, Hsu HW, Lim WX, Huang TL, Cheng YF. Diffusion-weighted imaging for identifying patients at high risk of tumor recurrence following liver transplantation. Cancer Imaging 2019; 19:74. [PMID: 31730015 PMCID: PMC6858682 DOI: 10.1186/s40644-019-0264-y] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2019] [Accepted: 11/07/2019] [Indexed: 12/15/2022] Open
Abstract
Background Tumor recurrence is the major risk factor affecting post-transplant survival. In this retrospective study, we evaluate the prognostic values of magnetic resonance (MR) diffusion-weighted imaging (DWI) in liver transplantation for hepatocellular carcinoma (HCC). Methods From April 2014 to September 2016, 106 HCC patients receiving living donor liver transplantation (LDLT) were enrolled. Nine patients were excluded due to postoperative death within 3 months and incomplete imaging data. The association between tumor recurrence, explant pathologic findings, and DWI parameters was analyzed (tumor-to-liver diffusion weighted imaging ratio, DWIT/L; apparent diffusion coefficients, ADC). The survival probability was calculated using the Kaplan–Meier method. Results Sixteen of 97 patients (16%) developed tumor recurrence during the follow-up period (median of 40.9 months; range 5.2–56.5). In those with no viable tumor (n = 65) on pretransplant imaging, recurrence occurred only in 5 (7.6%) patients. Low minimum ADC values (p = 0.001), unfavorable tumor histopathology (p < 0.001) and the presence of microvascular invasion (p < 0.001) were risk factors for tumor recurrence, while ADCmean (p = 0.111) and DWIT/L (p = 0.093) showed no significant difference between the groups. An ADCmin ≤ 0.88 × 10− 3 mm2/s was an independent factor associated with worse three-year recurrence-free survival (94.4% vs. 23.8%) and overall survival rates (100% vs. 38.6%). Conclusions Quantitative measurement of ADCmin is a promising prognostic indicator for predicting tumor recurrence after liver transplantation.
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Affiliation(s)
- Yi-Hsuan Chuang
- Liver Transplantation Program, Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Dapi Rd, Niaosong Dist, Kaohsiung, Taiwan, Republic of China
| | - Hsin-You Ou
- Liver Transplantation Program, Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Dapi Rd, Niaosong Dist, Kaohsiung, Taiwan, Republic of China
| | - Chun-Yen Yu
- Liver Transplantation Program, Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Dapi Rd, Niaosong Dist, Kaohsiung, Taiwan, Republic of China
| | - Chao-Long Chen
- Liver Transplantation Program, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Ching-Chun Weng
- Liver Transplantation Program, Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Dapi Rd, Niaosong Dist, Kaohsiung, Taiwan, Republic of China
| | - Leo Leung-Chit Tsang
- Liver Transplantation Program, Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Dapi Rd, Niaosong Dist, Kaohsiung, Taiwan, Republic of China
| | - Hsien-Wen Hsu
- Liver Transplantation Program, Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Dapi Rd, Niaosong Dist, Kaohsiung, Taiwan, Republic of China
| | - Wei-Xiong Lim
- Liver Transplantation Program, Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Dapi Rd, Niaosong Dist, Kaohsiung, Taiwan, Republic of China
| | - Tung-Liang Huang
- Liver Transplantation Program, Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Dapi Rd, Niaosong Dist, Kaohsiung, Taiwan, Republic of China
| | - Yu-Fan Cheng
- Liver Transplantation Program, Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Dapi Rd, Niaosong Dist, Kaohsiung, Taiwan, Republic of China.
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Ling LLL, Hsu CC, Yong CC, Elsarawy AM, Chan YC, Wang CC, Li WF, Lin TL, Kuo FY, Cheng YF, Lin LM, Chen CL, Lin CC. FDG-PET predicted unfavorable tumor histology in living donor liver transplant recipients; a retrospective cohort study. Int J Surg 2019; 69:124-131. [DOI: 10.1016/j.ijsu.2019.07.035] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2019] [Revised: 07/26/2019] [Accepted: 07/26/2019] [Indexed: 02/07/2023]
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Metal implants influence CT scan parameters leading to increased local radiation exposure: A proposal for correction techniques. PLoS One 2019; 14:e0221692. [PMID: 31442288 PMCID: PMC6707604 DOI: 10.1371/journal.pone.0221692] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2018] [Accepted: 08/13/2019] [Indexed: 12/14/2022] Open
Abstract
Metal implants not only deteriorate image quality, but also increase radiation exposure. The purpose of this study was to evaluate the effect of metal hip prosthesis on absorbed radiation dose and assess the efficacy of organ dose modulation (ODM) and metal artifact reduction (MAR) protocols on dose reduction. An anthropomorphic phantom was scanned with and without bilateral metal hip prostheses, and surface and deep level radiation doses were measured at the abdomen and pelvis. Finally, the absorbed radiation doses at pelvic and abdominal cavities in the reference, ODM, and two MAR scans (Gemstone spectral imaging, GE) were compared. The Mann Whitney-U test and Kruskal-Wallis test were performed to compare the volume CT dose index (CTDIvol) and mean absorbed radiation doses. Unilateral and bilateral metal hip prostheses increased CTDIVOL by 14.4% and 30.5%, respectively. MAR protocols decreased absorbed radiation doses in the pelvis. MAR showed the most significant dose reduction in the deep pelvic cavity followed by ODM. However, MAR protocols increased absorbed radiation doses in the upper abdomen. ODM significantly reduced absorbed radiation in the pelvis and abdomen. In conclusion, metal hip implants increased radiation doses in abdominopelvic CT scans. MAR and ODM techniques reduced absorbed radiation dose in abdominopelvic CT scans with metal hip prostheses.
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Hepatocellular carcinoma (HCC) versus non-HCC: accuracy and reliability of Liver Imaging Reporting and Data System v2018. Abdom Radiol (NY) 2019; 44:2116-2132. [PMID: 30798397 DOI: 10.1007/s00261-019-01948-x] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
PURPOSE The Liver Imaging Reporting and Data System (LI-RADS) was created to standardize the diagnostic criteria for hepatocellular carcinoma (HCC) and has undergone multiple revisions including a recent update in 2018 (v2018). The primary aim of this study was to determine the diagnostic performance and interrater reliability (IRR) of LI-RADS v2018 for distinguishing HCC from non-HCC primary hepatic malignancy in patients 'at-risk' for HCC. A secondary aim was to assess the impact of changes introduced in the v2018 diagnostic algorithm. METHODS This retrospective study combined a 10-year experience of pathologically proven primary liver malignancies from two large liver transplant centers. Two blinded readers independently evaluated each lesion and assigned a LI-RADS diagnostic category, additionally scoring all relevant imaging features. Changes in category based on the reader-provided features and the new v2018 criteria were assessed by a study coordinator. RESULTS The final study cohort comprised 105 HCCs and 73 non-HCC primarily liver malignancies. LI-RADS had a high specificity for distinguishing HCC from non-HCC (89% and 90% for reader 1 and reader 2, respectively), and IRR was moderate to substantial for final LI-RADS category and most features. Revision of the LI-RADS v2018 diagnostic algorithm resulted in very few changes [5 (2.8%) and 3 (1.7%) for reader 1 and reader 2, respectively] in overall lesion classification. CONCLUSION LI-RADS diagnostic categories and features had moderate to substantial IRR and high specificity for distinguishing HCC from non-HCC primary liver malignancy. Revision of LI-RADS v2018 diagnostic algorithm resulted in reclassification of very few lesions.
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Li DB, Si XY, Wang SJ, Zhou YM. Long-term outcomes of combined hepatocellular-cholangiocarcinoma after hepatectomy or liver transplantation: A systematic review and meta-analysis. Hepatobiliary Pancreat Dis Int 2019; 18:12-18. [PMID: 30442549 DOI: 10.1016/j.hbpd.2018.10.001] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2018] [Accepted: 10/17/2018] [Indexed: 02/05/2023]
Abstract
BACKGROUND Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is a rare primary liver malignancy. We conducted a systematic review and meta-analysis to assess the evidence available on the long-term outcomes of cHCC-CC patients after either hepatectomy or liver transplantation (LT). DATA SOURCES Relevant studies published between January 2000 and January 2018 were identified by searching PubMed and Embase and reviewed systematically. Data were pooled using a random-effects model. RESULTS A total of 42 observational studies involving 1691 patients (1390 for partial hepatectomy and 301 for LT) were included in the analysis. The median tumor recurrence and 5-year overall survival (OS) rates were 65% (range 38%-100%) and 29% (range 0-63%) after hepatectomy versus 54% (range 14%-93%) and 41% (range 16%-73%) after LT, respectively. Meta-analysis found no significant difference in OS and tumor recurrence between LT and hepatectomy groups. CONCLUSION Hepatectomy rather than LT should be considered as the prior treatment option for cHCC-CC.
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Affiliation(s)
- De-Bang Li
- Department III of General Surgery, the First Hospital of Lanzhou University, Lanzhou 730000, China
| | - Xiao-Ying Si
- Department of Hepatobiliary & Pancreatovascular Surgery, First Affiliated Hospital of Xiamen University, Xiamen 361003, China
| | - Shi-Jie Wang
- Department of Hepatobiliary & Pancreatovascular Surgery, First Affiliated Hospital of Xiamen University, Xiamen 361003, China
| | - Yan-Ming Zhou
- Department of Hepatobiliary & Pancreatovascular Surgery, First Affiliated Hospital of Xiamen University, Xiamen 361003, China.
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Stavraka C, Rush H, Ross P. Combined hepatocellular cholangiocarcinoma (cHCC-CC): an update of genetics, molecular biology, and therapeutic interventions. J Hepatocell Carcinoma 2018; 6:11-21. [PMID: 30643759 PMCID: PMC6312394 DOI: 10.2147/jhc.s159805] [Citation(s) in RCA: 93] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Combined hepatocellular cholangiocarcinoma (CC) is a rare and aggressive primary hepatic malignancy with significant histological and biological heterogeneity. It presents with more aggressive behavior and worse survival outcomes than either hepatocellular carcinoma or CC and remains a diagnostic challenge. An accurate diagnosis is crucial for its optimal management. Major hepatectomy with hilar node resection remains the mainstay of treatment in operable cases. Advances in the genetic and molecular characterization of this tumor will contribute to the better understanding of its pathogenesis and shape its future management.
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Affiliation(s)
- Chara Stavraka
- Department of Medical Oncology, Guy's Cancer, Guy's & St Thomas' NHS Foundation Trust, London, UK,
| | - Hannah Rush
- Department of Medical Oncology, Guy's Cancer, Guy's & St Thomas' NHS Foundation Trust, London, UK,
| | - Paul Ross
- Department of Medical Oncology, Guy's Cancer, Guy's & St Thomas' NHS Foundation Trust, London, UK, .,Department of Oncology, King's College Hospital NHS Foundation Trust, London, UK,
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How to utilize LR-M features of the LI-RADS to improve the diagnosis of combined hepatocellular-cholangiocarcinoma on gadoxetate-enhanced MRI? Eur Radiol 2018; 29:2408-2416. [PMID: 30552477 DOI: 10.1007/s00330-018-5893-1] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2018] [Revised: 10/23/2018] [Accepted: 11/14/2018] [Indexed: 12/21/2022]
Abstract
OBJECTIVES To investigate the diagnostic accuracy of each LR-M feature defined in version 2017 of the Liver Imaging Reporting and Data System (LI-RADS) and determine the optimal LR-M feature for differentiating combined hepatocellular-cholangiocarcinoma (cHCC-CCA) and hepatocellular carcinoma (HCC) on gadoxetate-enhanced magnetic resonance imaging (MRI). METHODS Ninety-nine patients with pathologically proven cHCC-CCA (n = 33) or HCC (n = 66) after surgery were identified. Two radiologists retrospectively assessed preoperative gadoxetate-enhanced MRI for features favoring non-HCC malignancies (LR-M features) according to LI-RADS version 2017. Multivariate logistic regression analysis was performed to determine the independent differential features. The sensitivity and specificity for diagnosing cHCC-CCA were calculated for each LR-M feature. RESULTS Targetoid appearance showed the highest sensitivity (75.8%, 95% confidence interval [CI] 60.6%, 87.3%) to correctly identify cHCC-CCA as LR-M. At least one LR-M feature was observed in 31 (93.9%) patients with cHCC-CCA and 34 (51.5%) patients with HCC. The sensitivity and specificity for diagnosing cHCC-CCA using the presence of any one of the LR-M features were 93.9% (95% CI 80.7, 98.9) and 48.5% (95% CI 41.9, 51.0), respectively. The presence of three LR-M features yielded the highest diagnostic accuracy of 80.8% (95% CI 72.1, 86.1) with a reduced sensitivity of 54.5% (95% CI 41.4, 62.5). CONCLUSION The majority of cHCC-CCA cases can be properly categorized as LR-M when any one of the LR-M features defined in the LI-RADS version 2017 is used as a determiner. However, approximately half of HCC cases also show at least one LR-M feature. KEY POINTS • Targetoid appearance, including rim APHE, peripheral "washout" appearance, and delayed central enhancement, was the LR-M feature that identified cHCC-CCA as a non-HCC malignancy with the highest sensitivity. • Most cHCC-CCA cases can be properly categorized as LR-M when the presence of any one of the LR-M features was used as the determiner. • Approximately half of HCC cases also showed at least one LR-M feature.
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Antwi SO, Habboush YY, Chase LA, Lee DD, Patel T. Response to Loco-Regional Therapy Predicts Outcomes After Liver Transplantation for Combined Hepatocellular-Cholangiocarcinoma. Ann Hepatol 2018; 17:969-979. [PMID: 30600299 DOI: 10.5604/01.3001.0012.7197] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND AIM Combined hepatocellular-cholangiocarcinoma (HCC-CCA) is a rare liver malignancy distinct from either hepatocellular carcinoma (HCC) or cholangiocarcinoma. Liver transplantation (LT) is not recommended for HCC-CCA because of suboptimal outcomes. Non-invasive diagnosis of HCC-CCA is extremely challenging; thus, some HCC-CCAs are presumed as HCC on imaging and listed for LT with the correct diagnosis ultimately made on explant pathology. We compared HCC-CCA with HCC to determine the utility of response to pre-transplant loco-regional therapy (LRT) in predicting outcomes for HCC-CCA after LT as a potential means of identifying appropriate HCC-CCA patients for LT. MATERIAL AND METHODS Retrospective review of 19 patients with pathologically confirmed HCC-CCA were individually matched to 38 HCC patients (1:2) based on age, sex, and Milan criteria at listing was performed. The modified response evaluation criteria in solid tumors was used to categorize patients as responders or non-responders to pre-transplant LRT based on imaging performed before and after LRT. Overall survival (OS) and recurrence-free survival (RFS) were examined. RESULTS OS at 3 years post-transplant was 74% for HCC-CCA and 87% for HCC. RFS at 3 years was 74% for HCC-CCA, and 87% for HCC. Among responders to LRT, the 3-year OS was 92% for HCC-CCA and 88% for HCC; among non-responders, 3-year OS was 43% for HCC-CCA and 83% for HCC. Higher 3-year OS was observed among HCC-CCA responders (77%) compared with HCC-CCA non-responders (23%). CONCLUSIONS OS was similarly high among.
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Affiliation(s)
- Samuel O Antwi
- Department of Transplantation, Mayo Clinic, Jacksonville, FL, USA
| | - Yacob Y Habboush
- Department of Transplantation, Mayo Clinic, Jacksonville, FL, USA
| | - Lori A Chase
- Department of Transplantation, Mayo Clinic, Jacksonville, FL, USA
| | - David D Lee
- Department of Transplantation, Mayo Clinic, Jacksonville, FL, USA
| | - Tushar Patel
- Department of Transplantation, Mayo Clinic, Jacksonville, FL, USA
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Jeon SK, Joo I, Lee DH, Lee SM, Kang HJ, Lee KB, Lee JM. Combined hepatocellular cholangiocarcinoma: LI-RADS v2017 categorisation for differential diagnosis and prognostication on gadoxetic acid-enhanced MR imaging. Eur Radiol 2018; 29:373-382. [PMID: 29955948 DOI: 10.1007/s00330-018-5605-x] [Citation(s) in RCA: 94] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2018] [Revised: 06/01/2018] [Accepted: 06/07/2018] [Indexed: 12/12/2022]
Abstract
OBJECTIVES To investigate the performance of the Liver Imaging Reporting and Data System (LI-RADS) v2017 for combined hepatocellular cholangiocarcinoma (cHCC-CCA) in the differential diagnosis from hepatocellular carcinoma (HCC) and prediction of prognosis on gadoxetic acid-enhanced MRI (Gd-EOB-MRI). METHODS Patients at high risk of HCC with pathologically confirmed cHCC-CCAs (n = 70) and a matched control of HCCs (n = 70) who had undergone Gd-EOB-MRI were included. LI-RADS category was assigned for each lesion by two radiologists. Imaging features and surgical outcomes were compared between cHCC-CCAs of LR-M and LR-5/4 using the χ2 test or Fisher's exact test. Recurrence-free survival (RFS) was estimated using Kaplan-Meier survival curves and compared using the log-rank test. RESULTS cHCC-CCAs and HCCs were categorised as LR-M, LR-5/4 and LR-TIV in 61.4% (43/70), 37.1% (26/70) and 1.4% (1/70) and 10.0% (7/70), 88.6% (62/70) and 1.4% (1/70), respectively. cHCC-CCAs of LR-5/4, in comparison to LR-M, showed significantly higher frequencies of major HCC features: arterial hyperenhancement (96.2% (25/26) vs. 58.1% (25/43), p = 0.001), washout appearance (80.8% (21/26) vs. 48.8% (21/43), p = 0.011) and enhancing capsule (34.6% (9/26) vs. 11.6% (5/43), p = 0.031). After curative surgery, patients with cHCC-CCAs of LR-M showed a higher early recurrence rate (≤ 6 months) than did those with LR-5/4 (27.8% (10/36) vs. 4.8% (1/21), p = 0.041), whereas no significant difference was observed in RFS (log-rank p = 0.084). CONCLUSIONS By using LI-RADS on Gd-EOB-MRI, a substantial proportion of cHCC-CCAs can be categorised as non-LR-M. In addition, cHCC-CCAs mimicking HCCs on imaging (LR-5/4) may indicate better surgical outcomes with regard to early recurrence than those of LR-M. KEY POINTS • cHCC-CCAs can be categorised as either LR-M or non-LR-M on Gd-EOB-MRI. • cHCC-CCAs of LR-5/4 frequently demonstrate major HCC imaging features. • LI-RADS categorisation may provide prognostic information after surgery in cHCC-CCAs.
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Affiliation(s)
- Sun Kyung Jeon
- Department of Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Korea
- Department of Radiology, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Korea
| | - Ijin Joo
- Department of Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Korea.
- Department of Radiology, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Korea.
| | - Dong Ho Lee
- Department of Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Korea
- Department of Radiology, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Korea
| | - Sang Min Lee
- Department of Radiology, Hallym University Sacred Heart Hospital, Anyang, Korea
| | - Hyo-Jin Kang
- Department of Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Korea
- Department of Radiology, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Korea
| | - Kyoung-Bun Lee
- Department of Pathology, Seoul National University Hospital, Seoul, Korea
| | - Jeong Min Lee
- Department of Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Korea
- Department of Radiology, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Korea
- Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul, Korea
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Ma KW, Chok KSH, She WH, Cheung TT, Chan ACY, Dai WC, Fung JYY, Lo CM. Hepatocholangiocarcinoma/intrahepatic cholangiocarcinoma: are they contraindication or indication for liver transplantation? A propensity score-matched analysis. Hepatol Int 2018; 12:167-173. [PMID: 29450868 DOI: 10.1007/s12072-018-9847-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2017] [Accepted: 01/29/2018] [Indexed: 02/08/2023]
Abstract
BACKGROUND Uncommon primary hepatic malignancies such as intrahepatic cholangiocarcinoma (ICC) and hepatocholangiocarcinoma (HCC-CC) were generally considered contraindications for liver transplantation(LT), and studies comparing the efficacy of LT and resection (LR) for ICC/HCC-CC were scarce. OBJECTIVE To compare the survival outcomes of ICC/HCC-CC patients treated by LT and LR in a propensity score-matched population. METHOD This is a retrospective study from 1995 to 2015. Consecutive patients with the pathological diagnosis of ICC or HCC-CC in the surgical specimens were included. All patients had either hepatectomy or LT with curative intent. Factors associated with survival were identified with multivariate analysis using cox-regression model. Propensity score-matched analysis was performed. RESULT There were 181 patients diagnosed to have ICC/HCC_CC. Nine patients received LT (all with incidental ICC/HCC-CC) and 172 received hepatectomy. The median follow-up period was 27.5 months. The median age was 60 years (range 3-86); Hepatitis B and C carrier status was found in 48.1 and 2.3% of the patients, respectively. The median tumor size was 6 cm and 71.3% of them had solitary tumor. Microvascular invasion was present in 47% of the patients. After propensity score matching, there were 54 (9 in LT and 45 in LR group) patients for analysis. Cox-regression analysis showed that early AJCC (7th) staging and LT were the independent factors associated with overall survival. Patients in the LT group had significantly better overall survival (5-year OS 77.8 vs 36.6%, log-rank p = 0.013). CONCLUSION ICC/HCC-CC are uncommon tumors with poor long-term oncological outcomes despite curative hepatectomy. Liver transplantation might be a better treatment option for patients with early ICC/HCC-CC.
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Affiliation(s)
- Ka Wing Ma
- Department of Surgery, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, China
| | - Kenneth Siu Ho Chok
- Department of Surgery, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, China.
- State Key Laboratory for Liver Research, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, China.
| | - Wong Hoi She
- Department of Surgery, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, China
| | - Tan To Cheung
- Department of Surgery, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, China
- State Key Laboratory for Liver Research, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, China
| | - Albert Chi Yan Chan
- Department of Surgery, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, China
- State Key Laboratory for Liver Research, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, China
| | - Wing Chiu Dai
- Department of Surgery, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, China
| | - James Yan Yue Fung
- Department of Medicine, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, China
- State Key Laboratory for Liver Research, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, China
| | - Chung Mau Lo
- Department of Surgery, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, China
- State Key Laboratory for Liver Research, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, China
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