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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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Szeto W, Mannan R. Other Primary Epithelial Neoplasms of the Liver. Adv Anat Pathol 2025:00125480-990000000-00146. [PMID: 40202295 DOI: 10.1097/pap.0000000000000494] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/10/2025]
Abstract
Primary liver carcinoma (PLC) is the sixth most common malignancy worldwide and the third leading cause of cancer-related mortalities. Hepatocellular carcinoma (HCC) is the most prevalent form of PLC, followed by intrahepatic cholangiocarcinoma (iCCA). In addition, there is a group of rarer PLCs that do not fit neatly into the HCC or iCCA categories. This review explores this heterogeneous group, including combined hepatocellular-cholangiocarcinoma (cHCC-CCA), intermediate cell carcinoma (ICC), mixed hepatocellular-neuroendocrine carcinoma, and undifferentiated primary liver carcinoma. cHCC-CCA is a rare subtype of PLC, characterized by both hepatocytic and cholangiocytic differentiation within the same tumor. The latest WHO classification (2019, fifth edition) redefined cHCC-CCA by eliminating the "stem cell subtypes" and emphasized that diagnosis should primarily rely on morphologic features, supported by immunohistochemical staining to better define subtypes. Intermediate cell carcinoma is a subtype of cHCC-CCA and is comprised of monomorphic tumor cells that exhibit characteristics intermediate between hepatocytes and cholangiocytes, with immunohistochemical expression of hepatocytic and cholangiocytic markers within the same cell. Another rare entity, combined HCC and neuroendocrine carcinoma (NEC), contains an admixture of HCC and NEC components within the same tumor. Undifferentiated primary liver carcinoma, on the other hand, lacks definitive lineage differentiation beyond an epithelial phenotype. These heterogeneous PLCs pose diagnostic challenges owing to their mixed/unusual histologic features and overlapping immunohistochemical markers. They tend to have poor prognoses, highlighting the critical importance of accurate and timely diagnosis.
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Affiliation(s)
- Wai Szeto
- Department of Pathology, City of Hope National Medical Center, Duarte, CA
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Deiana C, Palloni A, Mosca M, Vasuri F, Chillotti S, Tavolari S, De Biase D, Frega G, Giovannetti E, Brandi G. Case Report: Long lasting response with TKI for combined hepatocellular-cholangiocarcinoma. Front Oncol 2025; 15:1459705. [PMID: 40171268 PMCID: PMC11958941 DOI: 10.3389/fonc.2025.1459705] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2024] [Accepted: 02/20/2025] [Indexed: 04/03/2025] Open
Abstract
Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare primary liver cancer, with intermediate biological characteristics between hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). Given its rarity and the lack of robust data from randomized clinical trials, treatment is not standardized, and the choice on how to best manage the disease is left to the expertise of each institution. In the metastatic setting, given the more aggressive behavior of the CCA component, the usual approach is to start treatment with chemotherapy instead of tyrosine-kinase inhibitors (TKIs). We present a case report on a Caucasian male with a poor response to first-line treatment with chemotherapy directed against CCA, but with an excellent and long overall survival (OS) of 71 months, thanks to HCC-directed treatment with TKI. Here, we highlight the difficulty in selecting an appropriate treatment upfront for this rare cancer and we also discuss future perspectives regarding predictive tools, especially considering the recent genomic analysis of cHCC-CCA, and regarding the potential use of immunotherapy and target therapy.
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Affiliation(s)
- Chiara Deiana
- Medical Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Andrea Palloni
- Medical Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Mirta Mosca
- Dipartimento di Oncologia Medica, Azienda Socio Sanitaria Territoriale (ASST) Sette Laghi, Varese, Italy
| | - Francesco Vasuri
- Pathology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Stefano Chillotti
- Pathology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Simona Tavolari
- Medical Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Dario De Biase
- Solid Tumor Molecular Pathology Laboratory, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Pharmacy and Biotechnology (FaBit), University of Bologna, Bologna, Italy
| | - Giorgio Frega
- Osteoncology, Soft Tissue and Bone Sarcomas, Innovative Therapy Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Ortopedico Rizzoli, Bologna, Italy
| | - Elisa Giovannetti
- Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center (VUmc), Amsterdam, Netherlands
- Cancer Pharmacology Lab, Fondazione Pisana per la Scienza, Pisa, Italy
| | - Giovanni Brandi
- Medical Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
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Majeed NF, Macey M, Amirfarzan MB, Sharifi S, Wortman JR. MRI features of combined hepatocellular-cholangiocarcinoma. Abdom Radiol (NY) 2025; 50:169-184. [PMID: 39031181 DOI: 10.1007/s00261-024-04476-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Revised: 06/22/2024] [Accepted: 06/24/2024] [Indexed: 07/22/2024]
Abstract
Combined hepatocellular cholangiocarcinoma (cHCC-CCA) is a rare liver tumor which has a more aggressive behavior and worse survival outcome than hepatocellular carcinoma (HCC), with a prognosis similar to that of intrahepatic cholangiocarcinoma (iCCA). With limited literature on the appearance of this tumor on MRI, it remains a diagnostic challenge. In this review, we looked at the currently described MRI findings in this uncommon entity. Based on studies conducted to date, a mixed pattern at imaging has demonstrated the highest specificity, seen as a combination of areas showing progressive enhancement of the lesion, arterial enhancement with washout, and areas of arterial enhancement without washout and/or hypovascularity. Tumor markers may aid in identification, particularly in cases where the imaging appearance mimics that of isolated HCC or iCCA. Intratumoral heterogeneity leads to difficulties with pathologic diagnosis from sampling due to the possibility of an incorrect diagnosis if the biopsy specimen does not contain adequate tissue comprising both histologic components.
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Affiliation(s)
- Noor Fatima Majeed
- Department of Radiology, Emory University School of Medicine, Atlanta, GA, USA.
| | - Mathew Macey
- Department of Radiology, Lahey Hospital and Medical Center, Burlington, MA, USA
| | | | - Sheida Sharifi
- Department of Radiology, Lahey Hospital and Medical Center, Burlington, MA, USA
| | - Jeremy R Wortman
- Department of Radiology, Lahey Hospital and Medical Center, Burlington, MA, USA
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Xiao Y, Wu F, Hou K, Wang F, Zhou C, Huang P, Yang C, Zeng M. MR radiomics to predict microvascular invasion status and biological process in combined hepatocellular carcinoma-cholangiocarcinoma. Insights Imaging 2024; 15:172. [PMID: 38981992 PMCID: PMC11233482 DOI: 10.1186/s13244-024-01741-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Accepted: 06/09/2024] [Indexed: 07/11/2024] Open
Abstract
OBJECTIVES To establish an MRI-based radiomics model for predicting the microvascular invasion (MVI) status of cHCC-CCA and to investigate biological processes underlying the radiomics model. METHODS The study consisted of a retrospective dataset (82 in the training set, 36 in the validation set) and a prospective dataset (25 patients in the test set) from two hospitals. Based on the training set, logistic regression analyses were employed to develop the clinical-imaging model, while radiomic features were extracted to construct a radiomics model. The diagnosis performance was further validated in the validation and test sets. Prognostic aspects of the radiomics model were investigated using the Kaplan-Meier method and log-rank test. Differential gene expression analysis and gene ontology (GO) analysis were conducted to explore biological processes underlying the radiomics model based on RNA sequencing data. RESULTS One hundred forty-three patients (mean age, 56.4 ± 10.5; 114 men) were enrolled, in which 73 (51.0%) were confirmed as MVI-positive. The radiomics model exhibited good performance in predicting MVI status, with the area under the curve of 0.935, 0.873, and 0.779 in training, validation, and test sets, respectively. Overall survival (OS) was significantly different between the predicted MVI-negative and MVI-positive groups (median OS: 25 vs 18 months, p = 0.008). Radiogenomic analysis revealed associations between the radiomics model and biological processes involved in regulating the immune response. CONCLUSION A robust MRI-based radiomics model was established for predicting MVI status in cHCC-CCA, in which potential prognostic value and underlying biological processes that regulate immune response were demonstrated. CRITICAL RELEVANCE STATEMENT MVI is a significant manifestation of tumor invasiveness, and the MR-based radiomics model established in our study will facilitate risk stratification. Furthermore, underlying biological processes demonstrated in the radiomics model will offer valuable insights for guiding immunotherapy strategies. KEY POINTS MVI is of prognostic significance in cHCC-CCA, but lacks reliable preoperative assessment. The MRI-based radiomics model predicts MVI status effectively in cHCC-CCA. The MRI-based radiomics model demonstrated prognostic value and underlying biological processes. The radiomics model could guide immunotherapy and risk stratification in cHCC-CCA.
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Affiliation(s)
- Yuyao Xiao
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Fei Wu
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Kai Hou
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Fang Wang
- Shanghai United Imaging Intelligence Co. Ltd, Shanghai, China
| | - Changwu Zhou
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Peng Huang
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Chun Yang
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China.
| | - Mengsu Zeng
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China.
- Shanghai Institute of Medical Imaging, Shanghai, China.
- Department of Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China.
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Zhang J, Dong W, Liu W, Fu J, Liao T, Li Y, Huo L, Jia N. Preoperative evaluation of MRI features and inflammatory biomarkers in predicting microvascular invasion of combined hepatocellular cholangiocarcinoma. Abdom Radiol (NY) 2024; 49:710-721. [PMID: 38112787 PMCID: PMC10909765 DOI: 10.1007/s00261-023-04130-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Revised: 11/07/2023] [Accepted: 11/12/2023] [Indexed: 12/21/2023]
Abstract
PURPOSE Microvascular invasion (MVI) is a significant prognostic factor in combined hepatocellular cholangiocarcinoma (cHCC-CCA). However, its diagnosis relies on postoperative histopathologic analysis. This study aims to identify preoperative inflammatory biomarkers and MR-imaging features that can predict MVI in cHCC-CCA. METHODS This retrospective study enrolled 119 patients with histopathologically confirmed cHCC-CCA between January 2016 and December 2021. Two radiologists, unaware of the clinical data, independently reviewed all MR image features. Univariable and multivariable analyses were performed to determine the independent predictors for MVI among inflammatory biomarkers and MRI characteristics. The area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the diagnostic performance. RESULTS Multivariable logistic regression analysis identified four variables significantly associated with MVI (p < 0.05), including two inflammatory biomarkers [albumin-to-alkaline phosphatase ratio (AAPR) and aspartate aminotransferase-to-neutrophil ratio index (ANRI)] and two MRI features (non-smooth tumor margin and arterial phase peritumoral enhancement). A combined model for predicting MVI was constructed based on these four variables, with an AUC of 0.802 (95% CI 0.719-0.870). The diagnostic efficiency of the combined model was higher than that of the imaging model. CONCLUSION Inflammatory biomarkers and MRI features could be potential predictors for MVI in cHCC-CCA. The combined model, derived from inflammatory biomarkers and MRI features, showed good performance in preoperatively predicting MVI in cHCC-CCA patients.
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Affiliation(s)
- Juan Zhang
- Department of Radiology, Eastern Hepatobiliary Surgery Hospital, Third Affiliated Hospital of Naval Medical University, Shanghai, China
| | - Wei Dong
- Department of Pathology, Eastern Hepatobiliary Surgery Hospital, Third Affiliated Hospital of Naval Medical University, Shanghai, China
| | - Wanmin Liu
- Department of Radiology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Jiazhao Fu
- Department of Organ Transplantation, Changhai Hospital, First Affiliated Hospital of Naval Medical University, Shanghai, China
| | - Tian Liao
- Department of Ultrasound, Changsha Hospital of Traditional Chinese Medicine, Changsha, China
| | - Yinqiao Li
- School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, China
| | - Lei Huo
- Department of Radiology, Eastern Hepatobiliary Surgery Hospital, Third Affiliated Hospital of Naval Medical University, Shanghai, China.
| | - Ningyang Jia
- Department of Radiology, Eastern Hepatobiliary Surgery Hospital, Third Affiliated Hospital of Naval Medical University, Shanghai, China.
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Chu KJ, Kawaguchi Y, Wang H, Jiang XQ, Hasegawa K. Update on the Diagnosis and Treatment of Combined Hepatocellular Cholangiocarcinoma. J Clin Transl Hepatol 2024; 12:210-217. [PMID: 38343605 PMCID: PMC10851068 DOI: 10.14218/jcth.2023.00189] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2023] [Revised: 08/15/2023] [Accepted: 09/21/2023] [Indexed: 10/24/2024] Open
Abstract
Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a unique type of liver tumor that contains both hepatocellular carcinoma and cholangiocarcinoma components within a single tumor. The fifth edition of the World Health Organization classification provides a definition and diagnostic criteria for cHCC-CCA. However, the heterogeneous histomorphology and presentation resulting from variation of the proportion of each component poses challenges for clinical diagnosis and treatment. A diagnosis of cHCC-CCA may be suggested by the synchronous elevation of serum tumor markers for hepatocellular carcinoma and cholangiocarcinoma, a mixed enhancement pattern on imaging, and a discrepancy between the elevation of tumor marker and the imaging enhancement pattern. Histopathological examination using hematoxylin and eosin staining is considered the gold standard for diagnosing cHCC-CCA, and comprehensive examination of resection or biopsy specimens is crucial for an accurate diagnosis. Currently, there is no standard treatment for cHCC-CCA, and surgery is the mainstay. Anatomic hepatectomy with lymphadenectomy is among the recommended surgical procedures. The role of liver transplantation in the management of cHCC-CCA is still uncertain. Transarterial chemoembolization may be effective for unresectable cHCC-CCA, particularly for hypervascular tumors. However, the available evidence does not support systemic therapy for advanced cHCC-CCA. The prognosis of cHCC-CCA is generally poor, and there is no established staging system. Further research is needed to better understand the histogenesis and clinical management of cHCC-CCA. This review provides an overview of the current literature on cHCC-CCA with a focus on its clinical characteristics, pathological diagnosis, and management.
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Affiliation(s)
- Kai-Jian Chu
- Biliary Surgical Department No. 1, Eastern Hepatobiliary Surgical Hospital, The Naval Medical University, Shanghai, China
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yoshikuni Kawaguchi
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Han Wang
- Department of Pathology, Eastern Hepatobiliary Surgical Hospital, The Naval Medical University, Shanghai, China
| | - Xiao-Qing Jiang
- Biliary Surgical Department No. 1, Eastern Hepatobiliary Surgical Hospital, The Naval Medical University, Shanghai, China
| | - Kiyoshi Hasegawa
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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Lv TR, Hu HJ, Ma WJ, Liu F, Jin YW, Li FY. Meta-analysis of prognostic factors for overall survival and disease-free survival among resected patients with combined hepatocellular carcinoma and cholangiocarcinoma. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2024; 50:107279. [PMID: 38000116 DOI: 10.1016/j.ejso.2023.107279] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Revised: 11/09/2023] [Accepted: 11/15/2023] [Indexed: 11/26/2023]
Abstract
BACKGROUND Combined hepatocellular carcinoma and cholangiocarcinoma (CHCC-CC) is a rare subtype of primary liver malignancy and has been treated equally as intra-hepatic cholangiocarcinoma (IHCC) according to the 8th AJCC staging system. Owing to its rarity, its prognostic factors have been rarely explored and defined. METHODS PubMed, EMBASE, the Cochrane Library and Web of Science were searched up till January 1st, 2023 and eligible studies were restricted to studies reported prognostic factors of resected CHCC-CC. Standard Parmar modifications were used to determine pooled univariable hazard ratios (HRs). RESULTS A total of eleven studies with 1286 patients with resected classical CHCC-CC were finally included. Pooled results indicated that serum tumor biomarkers, including AFP, CA199, and CEA, were prognostic factors for postoperative overall survival (OS) and disease-free survival (DFS). Moreover, liver cirrhosis (P = 0.010), HBV infection (P = 0.030), and HCV infection (P < 0.001) were prognostic factors for OS. Age (HR = 1.03, P = 0.005) was a prognostic factor for DFS. Tumor size (OS: HR = 2, P < 0.001, DFS: HR = 2.15, P < 0.001), tumor number (OS: HR = 2.05, P < 0.001; DFS: HR = 1.96, P = 0.006), surgical margin (OS: HR = 2.33, <0.001001; DFS: HR = 2.35, P < 0.001), node metastasis (OS: HR = 2.96, P < 0.001; DFS: HR = 2.1, P < 0.001), vascular invasion (OS: HR = 2.17, P < 0.001; DFS: HR = 2.64, P < 0.001), and postoperative prophylactic trans-arterial chemotherapy embolization (PPTACE) (OS: HR = 1.67, P = 0.04; DFS: HR = 2.31, P < 0.001) were common prognostic factors for OS and DFS. CONCLUSION Various risk factors unmentioned in the 8th AJCC staging system were identified. These promising findings would facilitate a more personalized predictive model and help clinicians to stratify patients with different survival outcomes.
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Affiliation(s)
- Tian-Run Lv
- Department of Biliary Tract Surgery, General Surgrey, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Hai-Jie Hu
- Department of Biliary Tract Surgery, General Surgrey, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Wen-Jie Ma
- Department of Biliary Tract Surgery, General Surgrey, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Fei Liu
- Department of Biliary Tract Surgery, General Surgrey, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Yan-Wen Jin
- Department of Biliary Tract Surgery, General Surgrey, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Fu-Yu Li
- Department of Biliary Tract Surgery, General Surgrey, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China.
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Zhang J, Dong W, Li Y, Fu J, Jia N. Prediction of microvascular invasion in combined hepatocellular-cholangiocarcinoma based on preoperative contrast-enhanced CT and clinical data. Eur J Radiol 2023; 163:110839. [PMID: 37121101 DOI: 10.1016/j.ejrad.2023.110839] [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: 02/15/2023] [Revised: 04/11/2023] [Accepted: 04/14/2023] [Indexed: 05/02/2023]
Abstract
OBJECTIVE Microvascular invasion (MVI) is significantly associated with prognosis in combined hepatocellular-cholangiocarcinoma (cHCC-CCA) patients. The study aimed to explore the value of preoperative contrast-enhanced CT (CECT) features and clinical data in predicting MVI of cHCC-CCA. METHODS A total of 33 patients with MVI-positive and 27 with MVI-negative were enrolled, and underwent preoperative CECT imaging from January 2016 to December 2021. Preoperative clinical data and CECT imaging features were retrospectively analyzed. Univariable and multivariable logistic regression analysis were performed to identify potential predictors of MVI in cHCC-CCA. The diagnostic performance was evaluated by the receiver operating characteristic (ROC) curve and its area under the curve (AUC) value. RESULTS The mean age of the patients was 54.0 ± 10.3 years, and 53 of the 60 patients (88.3%) were male. Preoperative imaging features on CECT (non-smooth contour and arterial phase peritumoral enhancement) and clinical data (hepatitis B virus (HBV) infection and protein induced by vitamin K absence or antagonist-II (PIVKA-II)) were highly distinct between those in MVI-positive group and MVI-negative group. On multivariable logistic analysis, arterial phase peritumoral enhancement (odds ratio (OR), 6.514; 95% confidence interval (CI), 1.588-26.728, p = 0.012) and high serum PIVKA-II level (OR, 6.810; 95% CI, 1.796-25.820, p = 0.005) were independent predictors associated with MVI of cHCC-CCA. The combination of these two predictors had high sensitivity (31/33, 93.9%; 95% CI, 80.4% - 98.3%) in the prediction of MVI with an area under the receiver operating characteristic (ROC) curve of 0.763 (95% CI, 0.635-0.863). CONCLUSIONS The findings indicated that arterial phase peritumoral enhancement on preoperative CECT and high serum PIVKA-II level were identified as potential predictors for MVI in cHCC-CCA patients.
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Affiliation(s)
- Juan Zhang
- Department of Radiology, Eastern Hepatobilliary Surgery Hospital, Third Affiliated Hospital of Naval Medical University, Shanghai 200438, China
| | - Wei Dong
- Department of Pathology, Eastern Hepatobilliary Surgery Hospital, Third Affiliated Hospital of Naval Medical University, Shanghai 200438, China
| | - Yinqiao Li
- School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China
| | - Jiazhao Fu
- Department of Organ Transplantation, Changhai Hospital, First Affiliated Hospital of Naval Medical University, Shanghai 200433, China.
| | - Ningyang Jia
- Department of Radiology, Eastern Hepatobilliary Surgery Hospital, Third Affiliated Hospital of Naval Medical University, Shanghai 200438, China.
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Wu Y, Liu H, Chen Y, Zeng J, Huang Q, Zhang J, Zeng Y, Liu J. Prognostic significance of three-tiered pathological classification for microvascular invasion in patients with combined hepatocellular-cholangiocarcinoma following hepatic resection. Cancer Med 2023; 12:5233-5244. [PMID: 36354141 PMCID: PMC10028161 DOI: 10.1002/cam4.5328] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2022] [Revised: 08/01/2022] [Accepted: 09/12/2022] [Indexed: 11/12/2022] Open
Abstract
BACKGROUND AND OBJECTIVES Previous studies have reported that the microvascular invasion three-tiered grading (MiVI-TTG) scheme is a better prognostic predictor than the two-tiered microvascular invasion (MiVI) grading scheme in hepatocellular carcinoma. This study aims to explore the prognostic significance of MiVI-TTG in patients undergoing liver resection for combined hepatocellular-cholangiocarcinoma (cHCC) and to explore the risk factors for MiVI in cHCC. METHODS This research included 208 patients graded as M0, M1, or M2 using the MiVI-TTG scheme. Predictive performance was assessed by Cox regression analysis, Kaplan-Meier curve with Log rank test, Harrell's c-index, and time-dependent areas under the receiver operating characteristic curve (tdAUC). The clinical utility of the two schemes was evaluated by decision cure analysis (DCA). The risk factors for MiVI were evaluated using logistic regression analysis. RESULTS Among 208 cHCC patients, the proportions of M0, M1 and M2 were 38.9%, 36.5%, and 24.5%, respectively. Patients with severe MiVI status had worse recurrence-free survival and overall survival (OS) based on Kaplan-Meier analysis. M1, M2, and MiVI-positive were independent risk factors for early recurrence, while M2 and MiVI-positive were associated with overall survival (OS). MiVI-TTG had a larger c-index, tdAUC, and net benefit rate than the two-tiered MiVI grading scheme for predicting recurrence free survival and OS. AFP≥400 ng/ml was the independent risk factor for MiVI, and satellite nodules were independent risk factors for M2. CONCLUSIONS MiVI-TTG has a greater prognostic value than the two-tiered MiVI grading scheme in patients undergoing hepatic resection for cHCC.
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Affiliation(s)
- Yijun Wu
- Department of Hepatobiliary SurgeryMengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhouPeople's Republic of China
| | - Hongzhi Liu
- Department of Hepatobiliary SurgeryMengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhouPeople's Republic of China
| | - Yifan Chen
- Shengli Clinical Medical College of Fujian Medical University
| | - Jianxing Zeng
- Department of Hepatobiliary SurgeryMengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhouPeople's Republic of China
| | - Qizhen Huang
- Department of Hepatobiliary SurgeryMengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhouPeople's Republic of China
| | - Jinyu Zhang
- Department of Hepatobiliary SurgeryMengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhouPeople's Republic of China
| | - Yongyi Zeng
- Department of Hepatobiliary SurgeryMengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhouPeople's Republic of China
| | - Jingfeng Liu
- Fujian Medical University Cancer Hospital & Fujian Cancer HospitalFuzhouFujianPeople's Republic of China
- The Big Data Institute of Southeast Hepatobiliary Health InformationMengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhouPeople's Republic of China
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Xiao Y, Zheng X, Zhou C, Huang P, Wu F, Yang C, Zeng M. Combined hepatocellular carcinoma-cholangiocarcinoma with a predominant HCC component: better survival and MRI-based prediction. Eur Radiol 2023; 33:1412-1421. [PMID: 36112193 DOI: 10.1007/s00330-022-09131-5] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Revised: 07/22/2022] [Accepted: 08/29/2022] [Indexed: 02/03/2023]
Abstract
OBJECTIVES To determine the optimal cutoff value of HCC% for predicting the outcome of patients with combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CCA) and to investigate how preoperative MR features based on the Liver Imaging Reporting and Data System (LI-RADS ver. 2018) are related to the HCC% in cHCC-CCA. METHODS The study enrolled 107 patients pathologically confirmed to have single cHCC-CCA according to the 2019 WHO classification. A receiver operating characteristic (ROC) curve was used to find the optimal cutoff value of HCC% based on overall survival (OS). The preoperative MR imaging features and clinicopathological findings were retrospectively evaluated and compared between the high HCC% and low HCC% groups. RESULTS In total, 107 patients (mean age, males vs. females: 56.6 ± 10.7 years vs. 54.2 ± 12.8 years) were evaluated. Analysis of the relationship between HCC% and OS by ROC curve suggested that the optimal cutoff value was 65%, by which 51 (47.7%) patients were assigned to the high HCC% group. LI-RADS categorization (OR = 3.657, p = 0.006 vs. OR = 4.075, p = 0.004) and serum carcinoembryonic antigen (CEA) >5 ng/mL (OR = 0.348, p = 0.089 vs. OR = 0.298, p = 0.040) were significant predictors for HCC% in cHCC-CCA in both univariate and multivariate analysis. CONCLUSIONS cHCC-CCA patients with HCC components higher than 65% tend to exhibit better overall survival, and MRI-based LI-RADS categorization and serum CEA level are valuable for identifying HCC% in cHCC-CCA preoperatively. KEY POINTS • cHCC-CCA patients with HCC components higher than 65% tend to exhibit better overall survival. • MRI-based LI-RADS categorization and serum CEA level were significant predictors for HCC% in cHCC-CCA in both univariate and multivariate analyses and valuable for identifying HCC% in cHCC-CCA preoperatively.
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Affiliation(s)
- Yuyao Xiao
- Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
| | - Xinde Zheng
- Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
| | - Changwu Zhou
- Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China.,Shanghai Institute of Medical Imaging, Shanghai, China
| | - Peng Huang
- Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
| | - Fei Wu
- Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, 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. .,Shanghai Institute of Medical Imaging, Shanghai, China. .,Department of Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China.
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12
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Combining Preoperative Clinical and Imaging Characteristics to Predict MVI in Hepatitis B Virus-Related Combined Hepatocellular Carcinoma and Cholangiocarcinoma. J Pers Med 2023; 13:jpm13020246. [PMID: 36836479 PMCID: PMC9968216 DOI: 10.3390/jpm13020246] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Revised: 01/23/2023] [Accepted: 01/28/2023] [Indexed: 01/31/2023] Open
Abstract
BACKGROUND Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CCA) is a rare form of primary liver malignancy. Microvascular invasion (MVI) indicates poor postsurgical prognosis in cHCC-CCA. The objective of this study was to investigate preoperative predictors of MVI in hepatitis B virus (HBV) -related cHCC-CCA patients. METHODS A total of 69 HBV-infected patients with pathologically confirmed cHCC-CCA who underwent hepatectomy were included. Univariate and multivariate analyses were conducted to determine independent risk factors that were then incorporated into the predictive model associated with MVI. Receiver operating characteristic analysis was used to assess the predictive performance of the new model. RESULTS For the multivariate analysis, γ-glutamyl transpeptidase (OR, 3.69; p = 0.034), multiple nodules (OR, 4.41; p = 0.042) and peritumoral enhancement (OR, 6.16; p = 0.004) were independently associated with MVI. Active replication of HBV indicated by positive HBeAg showed no differences between MVI-positive and MVI-negative patients. The prediction score using the independent predictors achieved an area under the curve of 0.813 (95% CI 0.717-0.908). A significantly lower recurrence-free survival was observed in the high-risk group with a score of ≥1 (p < 0.001). CONCLUSION γ-glutamyl transpeptidase, peritumoral enhancement and multiple nodules were independent preoperative predictors of MVI in HBV-related cHCC-CCA patients. The established prediction score demonstrated satisfactory performance in predicting MVI pre-operatively and may facilitate prognostic stratification.
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13
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Li Y, Ni X, Liu X, Yang C, Wang Y, Lu X, Zhou C. Prognosis of Primary Liver Cancer Based on LI-RADS Classification with Extracellular Agent-Enhanced MRI. J Hepatocell Carcinoma 2023; 10:399-411. [PMID: 36926054 PMCID: PMC10010934 DOI: 10.2147/jhc.s394840] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2022] [Accepted: 02/20/2023] [Indexed: 03/11/2023] Open
Abstract
Objective The prognostic value of the Liver Imaging Reporting and Data System (LI-RADS) 2018 in differentiating hepatocellular carcinoma (HCC) from other primary liver cancers (PLC) with cirrhosis is unclear. We aim to evaluate the value of LI-RADS 2018 with agent-enhanced MRI in the postoperative prognosis of PLC patients with cirrhosis. Methods Between 2016 and 2021, 432 patients with cirrhosis and surgically proven single primary liver cancer were retrospectively evaluated. Two radiologists evaluated the preoperative MRI features independently and assigned each lesion a LI-RADS category. Overall survival (OS), recurrence-free survival (RFS), and their associated factors were evaluated by using the Kaplan-Meier method, Log rank test, and Cox proportional hazards model. Results The mean age of 432 patients (239 HCCs, 93 ICCs, and 100 cHCC-CCAs) was 57.27±10.92 years. The LR-M category showed poorer OS and RFS than the LR-4 or LR-5 category did for all primary liver cancers (P <0.001 for both), and so did HCCs with tumor size less than 30mm (P =0.003 and P =0.04, respectively). In the multivariable analysis, the LI-RADS category and tumor size > 30 mm had independent correlations with OS and RFS (all P < 0.05). Multivariable Cox analysis identified rim arterial phase hyperenhancement (APHE) as independent determinants of poor OS and RFS in primary liver cancers (all P < 0.05). Conclusion The LI-RADS categories can predict the postsurgical prognosis of primary liver cancers independently.
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Affiliation(s)
- Yubo Li
- Department of MRI, Henan Provincial Hospital of Traditional Chinese Medicine (the Second Affiliated Hospital of Henan University of Traditional Chinese Medicine), Zhengzhou, People's Republic of China.,Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.,Shanghai Institute of Medical Imaging, Shanghai, People's Republic of China.,Department of Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
| | - Xiaoyan Ni
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.,Shanghai Institute of Medical Imaging, Shanghai, People's Republic of China.,Department of Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
| | - Xinai Liu
- Department of MRI, Henan Provincial Hospital of Traditional Chinese Medicine (the Second Affiliated Hospital of Henan University of Traditional Chinese Medicine), Zhengzhou, People's Republic of China
| | - Chun Yang
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.,Shanghai Institute of Medical Imaging, Shanghai, People's Republic of China.,Department of Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
| | - Yi Wang
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.,Department of Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
| | - Xin Lu
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.,Shanghai Institute of Medical Imaging, Shanghai, People's Republic of China.,Department of Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
| | - Changwu Zhou
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.,Shanghai Institute of Medical Imaging, Shanghai, People's Republic of China.,Department of Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
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14
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Zhang G, Chen BW, Yang XB, Wang HY, Yang X, Xie FC, Chen XQ, Yu LX, Shi J, Lu YY, Zhao HT. Prognostic analysis of patients with combined hepatocellular-cholangiocarcinoma after radical resection: A retrospective multicenter cohort study. World J Gastroenterol 2022; 28:5968-5981. [PMID: 36405111 PMCID: PMC9669829 DOI: 10.3748/wjg.v28.i41.5968] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Revised: 09/24/2022] [Accepted: 10/14/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a form of rare primary liver cancer that combines intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma.
AIM To investigate overall survival (OS) and recurrence-free survival (RFS) after radical resection in patients with cHCC-CCA, and the clinicopathological factors affecting prognosis in two center hospitals of China.
METHODS We reviewed consecutive patients with cHCC-CCA who received radical resection between January 2005 and September 2021 at Peking Union Medical College and the 5th Medical Center of the PLA General Hospital retrospectively. Regular follow-up and clinicopathological characteristics were systematic collected for baseline and prognostic analysis.
RESULTS Our study included 95 patients who received radical resection. The majority of these patients were male and 82.7% of these patients were infected with HBV. The mean tumor size was 4.5 cm, and approximately 40% of patients had more than one lesion. The median OS was 26.8 (95%CI: 18.5-43.0) mo, and the median RFS was 7.27 (95%CI: 5.83-10.3) mo. Independent predictors of OS were CA19-9 ≥ 37 U/mL (HR = 8.68, P = 0.002), Child-Pugh score > 5 (HR = 5.52, P = 0.027), tumor number > 1 (HR = 30.85, P = 0.002), tumor size and transarterial chemoembolization (TACE) after surgery (HR = 0.2, P = 0.005).
CONCLUSION The overall postoperative survival of cHCC-CCA patients is poor, and most patients experience relapse within a short period of time after surgery. Preoperative tumor biomarker (CA19-9, alpha-fetoprotein) levels, tumor size, and Child-Pugh score can significantly affect OS. Adjuvant TACE after surgery prolongs RFS, suggesting that TACE is a possible option for postoperative adjuvant therapy in patients with cHCC-CCA.
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Affiliation(s)
- Ge Zhang
- Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Bo-Wen Chen
- 302 Clinical Medical School, Peking University, Beijing 100039, China
- Senior Department of Hepatology, The 5th Medical Center of the PLA General Hospital, Beijing 100039, China
| | - Xiao-Bo Yang
- Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Huai-Yuan Wang
- Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Xu Yang
- Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Fu-Cun Xie
- Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Xiang-Qi Chen
- Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Ling-Xiang Yu
- Senior Department of Hepatology, The 5th Medical Center of the PLA General Hospital, Beijing 100039, China
| | - Jie Shi
- Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Yin-Ying Lu
- 302 Clinical Medical School, Peking University, Beijing 100039, China
- Senior Department of Hepatology, The 5th Medical Center of the PLA General Hospital, Beijing 100039, China
- Guangdong Key Laboratory of Epigenetics, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518055, Guangdong Province, China
| | - Hai-Tao Zhao
- Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
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15
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Analysis of viral integration reveals new insights of oncogenic mechanism in HBV-infected intrahepatic cholangiocarcinoma and combined hepatocellular-cholangiocarcinoma. Hepatol Int 2022; 16:1339-1352. [PMID: 36123506 DOI: 10.1007/s12072-022-10419-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2022] [Accepted: 08/24/2022] [Indexed: 11/04/2022]
Abstract
BACKGROUND Integration of HBV DNA into the human genome could progressively contribute to hepatocarcinogenesis. Both intrahepatic cholangiocarcinoma (ICC) and combined hepatocellular-cholangiocarcinoma (CHC) are known to be associated with HBV infection. However, the integration of HBV and mechanism of HBV-induced carcinogenesis in ICC and CHC remains unclear. METHODS 41 patients with ICC and 20 patients with CHC were recruited in the study. We conducted HIVID analysis on these 61 samples to identify HBV integration sites in both the tumor tissues and adjacent non-tumor liver tissues. To further explore the effect of HBV integration on gene alteration, we selected paired tumors and adjacent non-tumor liver tissues from 3 ICC and 4 CHC patients for RNA-seq and WGS. RESULTS We detected 493 HBV integration sites in ICC patients, of which 417 were from tumor samples and 76 were from non-tumor samples. And 246 HBV integration sites were detected in CHC patients, of which 156 were located in the genome of tumor samples and 90 were in non-tumor samples. Recurrent HBV integration events were detected in ICC including TERT, ZMAT4, MET, ANKFN1, PLXNB2, and in CHC like TERT, ALKBH5. Together with our established data of HBV-infected hepatocellular carcinoma, we found that HBV preferentially integrates into the specific regions which may affect the gene expression and regulation in cells and involved in carcinogenesis. We further performed genomic and transcriptomic sequencing of three ICC and four CHC patients, and found that HBV fragments could integrate near some important oncogene like TERT, causing large-scale genome variations on nearby genomic sequences, and at the same time changing the expression level of the oncogenes. CONCLUSION Comparative analysis demonstrates numerous newly discovered mutational events in ICC and CHC resulting from HBV insertions in the host genome. Our study provides an in-depth biological and clinical insights into HBV-induced ICC and CHC.
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16
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Wang WQ, Li J, Liang BY, Lv X, Zhu RH, Wang JL, Huang ZY, Yang SH, Zhang EL. Anatomical liver resection improves surgical outcomes for combined hepatocellular-cholangiocarcinoma: A propensity score matched study. Front Oncol 2022; 12:980736. [PMID: 36059669 PMCID: PMC9433922 DOI: 10.3389/fonc.2022.980736] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Accepted: 07/29/2022] [Indexed: 11/13/2022] Open
Abstract
BackgroundThe efficacies of anatomical resection (AR) and non-anatomical resection (NAR) in the treatment of combined hepatocellular-cholangiocarcinoma (cHCC-CCA) remain unclear. This study aimed to compare the prognostic outcomes of AR with those of NAR for cHCC-CCA.MethodPatients diagnosed with pathology-confirmed cHCC-CCA, and who underwent curative resection at Tongji hospital between January 2010 and December 2019 were included in this retrospective study. A one-to-one propensity score matching (PSM) analysis was used to compare the long-term outcomes of AR to those of NAR.ResultsA total of 105 patients were analyzed, of whom 48 (45.7%) and 57 (54.3%) underwent AR and NAR, respectively. There were no significant differences in short-term outcomes between the two groups, including duration of postoperative hospital stay, the incidence of perioperative complications, and incidence of 30-day mortality. However, both, the 5-year overall survival (OS) and recurrence-free survival (RFS) rates of AR were significantly better than those of NAR (40.5% vs. 22.4%, P=0.002; and 37.3% vs. 14.4%, P=0.002, respectively). Multivariate analysis showed that NAR, multiple tumors, larger-sized tumors (>5 cm), cirrhosis, lymph node metastasis, and vascular invasion were independent risk factors for poor prognoses. Stratified analysis demonstrated similar outcomes following AR versus NAR for patients with tumors > 5cm in diameter, while AR had better survival than NAR in patients with tumors ≤5 cm in diameter. After PSM, when 34 patients from each group were matched, the 5-year OS and RFS rates of AR were still better than those of NAR.ConclusionPatients with cHCC-CCA who underwent AR had better long-term surgical outcomes than those who underwent NAR, especially for those with tumors ≤5 cm in diameter. However, no differences in the risk of surgical complications were detected between the two groups.
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Affiliation(s)
- Wen-qiang Wang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jian Li
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Bin-yong Liang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xing Lv
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Rong-hua Zhu
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jin-lin Wang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zhi-yong Huang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Shu-hong Yang
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- *Correspondence: Er-lei Zhang, ; Shu-hong Yang,
| | - Er-lei Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- *Correspondence: Er-lei Zhang, ; Shu-hong Yang,
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17
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Guo HL, Lu XZ, Hu HT, Ruan SM, Zheng X, Xie XY, Lu MD, Kuang M, Shen SL, Chen LD, Wang W. Contrast-Enhanced Ultrasound-Based Nomogram: A Potential Predictor of Individually Postoperative Early Recurrence for Patients With Combined Hepatocellular-Cholangiocarcinoma. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2022; 41:1925-1938. [PMID: 34751450 DOI: 10.1002/jum.15869] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Revised: 10/17/2021] [Accepted: 10/22/2021] [Indexed: 12/17/2022]
Abstract
PURPOSES To evaluate the postsurgical prognostic implication of contrast-enhanced ultrasound (CEUS) for combined hepatocellular-cholangiocarcinoma (CHC). To build a CEUS-based early recurrence prediction classifier for CHC, in comparison with tumor-node-metastasis (TNM) staging. METHODS The CEUS features and clinicopathological findings of each case were analyzed, and the Liver Imaging Reporting and Data System categories were assigned. The recurrence-free survival associated factors were evaluated by Cox proportional hazard model. Incorporating the independent factors, nomograms were built to estimate the possibilities of 3-month, 6-month, and 1-year recurrence and whose prognostic value was determined by time-dependent receiver operating characteristics, calibration curves, and hazard layering efficiency validation, comparing with TNM staging system. RESULTS In the multivariable analysis, the levels of carbohydrate antigen 19-9, prothrombin time and total bilirubin, and tumor shape, the Liver Imaging Reporting and Data System category were independent factors for recurrence-free survival. The LR-M category showed longer recurrence-free survival than did the LR-4/5 category. The 3-month, 6-month, and 1-year area under the curves of the CEUS-clinical nomogram, clinical nomogram, and TNM staging system were 0.518, 0.552, and 0.843 versus 0.354, 0.240, and 0.624 (P = .048, .049, and .471) vs. 0.562, 0.545, and 0.843 (P = .630, .564, and .007), respectively. The calibration curves of the CEUS-clinical model at different prediction time pionts were all close to the ideal line. The CEUS-clinical model effectively stratified patients into groups of high and low risk of recurrence in both training and validation set, while the TNM staging system only works on the training set. CONCLUSIONS Our CEUS-clinical nomogram is a reliable early recurrence prediction tool for hepatocellular-cholangiocarcinoma and helps postoperative risk stratification.
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Affiliation(s)
- Huan-Ling Guo
- Department of Medical Ultrasonics, Ultrasomics Artificial Intelligence X-Lab, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Xiao-Zhou Lu
- Department of Traditional Chinese Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Hang-Tong Hu
- Department of Medical Ultrasonics, Ultrasomics Artificial Intelligence X-Lab, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Si-Min Ruan
- Department of Medical Ultrasonics, Ultrasomics Artificial Intelligence X-Lab, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Xin Zheng
- Department of Medical Ultrasonics, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
| | - Xiao-Yan Xie
- Department of Medical Ultrasonics, Ultrasomics Artificial Intelligence X-Lab, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Ming-De Lu
- Department of Medical Ultrasonics, Ultrasomics Artificial Intelligence X-Lab, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Ming Kuang
- Department of Medical Ultrasonics, Ultrasomics Artificial Intelligence X-Lab, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Shun-Li Shen
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Li-Da Chen
- Department of Medical Ultrasonics, Ultrasomics Artificial Intelligence X-Lab, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Wei Wang
- Department of Medical Ultrasonics, Ultrasomics Artificial Intelligence X-Lab, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
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Chen Y, Lu Q, Zhu Y, Huang B, Dong Y, Wang W. Prediction of Microvascular Invasion in Combined Hepatocellular-Cholangiocarcinoma Based on Pre-operative Clinical Data and Contrast-Enhanced Ultrasound Characteristics. ULTRASOUND IN MEDICINE & BIOLOGY 2022; 48:1190-1201. [PMID: 35397928 DOI: 10.1016/j.ultrasmedbio.2022.02.014] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/13/2021] [Revised: 01/27/2022] [Accepted: 02/11/2022] [Indexed: 06/14/2023]
Abstract
The goal of the study described here was to define the predictive value of pre-operative clinical information and contrast-enhanced ultrasound (CEUS) imaging characteristics in combined hepatocellular-cholangiocarcinoma (CHC) patients with microvascular invasion (MVI). Seventy-six patients with pathologically confirmed CHC were enrolled in this study, comprising 18 patients with MVI-positive status and 58 with MVI-negative CHC nodules. The pre-operative clinical data and CEUS imaging features were retrospectively analyzed. Univariate and multivariate analyses were performed to identify the potential predictors of MVI in CHC. Recurrence-free survival (RFS) after hepatectomy was compared between patients with different MVI status using the log-rank test and Kaplan-Meier survival curves. Univariate analysis indicated that the following parameters of patients with CHC significantly differed between the MVI-positive and MVI-negative groups (p<0.05): tumor size, α-fetoprotein ≥400 ng/mL, enhancement patterns in arterial phase and marked washout during the portal venous phase on CEUS. On multivariate logistic regression analysis, only the CEUS characteristics of heterogeneous enhancement (odds ratio = 6.807; 95% confidence interval [CI]: 1.099, 42.147; p = 0.039) and marked washout (odds ratio = 4.380; 95% CI: 1.050,18.270; p = 0.043) were identified as independent predictors of MVI in CHC. The combination of the two risk factors in predicting MVI achieved a better diagnostic performance than each parameter alone, with an area under the receiver operating characteristic curve of 0.736 (0.622, 0.830). After hepatectomy, CHC patients with MVI exhibited earlier recurrence compared with those without MVI (hazard ratio = 1.859; 95% CI: 0.8699-3.9722, p = 0.046). The CEUS imaging features of heterogeneous enhancement in the arterial phase and marked washout during the portal venous phase were the potential predictors of MVI in CHC. Aside from that, CHC patients with MVI had an earlier recurrence rate than those without MVI after surgery.
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Affiliation(s)
- Yanling Chen
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Qing Lu
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yuli Zhu
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Beijian Huang
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China; Institute of Ultrasound Medicine and Engineering, Fudan University, Shanghai, China
| | - Yi Dong
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China; Shanghai Institute of Medical Imaging, Shanghai, China
| | - Wenping Wang
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China; Institute of Ultrasound Medicine and Engineering, Fudan University, Shanghai, China; Shanghai Institute of Medical Imaging, Shanghai, China.
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Zhou YW, Li QF, Chen YY, Wang K, Pu D, Chen XR, Li CH, Jiang L, Wang Y, Li Q, Yang Y, Gou HF, Bi F, Liu JY, Chen Y, Qiu M. Clinicopathologic features, treatment, survival, and prognostic factors of combined hepatocellular and cholangiocarcinoma: A nomogram development based on SEER database and validation in multicenter study. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2022; 48:1559-1566. [PMID: 35115213 DOI: 10.1016/j.ejso.2022.01.023] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Revised: 10/07/2021] [Accepted: 01/23/2022] [Indexed: 02/05/2023]
Abstract
PURPOSE The aim of the study was to comprehensively understand the combined hepatocellular and cholangiocarcinoma (CHC) and develop a nomogram for prognostic prediction of CHC. METHODS Data were collected from the Surveillance, Epidemiology and End Results (SEER) database (year 2004-2014). Propensity-score matching (PSM) was used to match the demographic characteristic of the CHC versus hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). A nomogram model was established to predict the prognosis in terms of cancer specific survival (CSS). The established nomogram was externally validated by a multicenter cohort. RESULTS A total of 71,756 patients enrolled in our study including 62,877 HCC patients, 566 CHC patients, and 8303 ICC patients. The CHC, HCC, and ICC are not exactly similar in clinical characteristic. After PSM, the CSS of CHC was better than HCC but comparable to ICC. Tumor size, M stage, surgery, chemotherapy, and surgery were independently prognostic factors of CHC and were included in the establishment of novel nomogram. The c-index of the novel nomogram in SEER training set and multicenter validation was 0.779 and 0.780, respectively, which indicated that the model was with better discrimination power. In addition, decision curve analyses proved the favorable potential clinical effect of the predictive model. Lastly, a risk classification based on nomogram also verified the reliability of the model. CONCLUSION CHC had better survival than HCC but was comparable to ICC. The nomogram was established based on tumor size, M stage, chemotherapy, surgery, and radiotherapy and well validated by external multicenter cohort.
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Affiliation(s)
- Yu-Wen Zhou
- Department of Biotherapy, Cancer Center, West China Hospital of Sichuan University, Chengdu, China; Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, China
| | - Qing-Fang Li
- Department of Biotherapy, Cancer Center, West China Hospital of Sichuan University, Chengdu, China; Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, China
| | - Yue-Yun Chen
- Department of Biotherapy, Cancer Center, West China Hospital of Sichuan University, Chengdu, China; Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, China
| | - Kai Wang
- Institute for Emergency Medicine and Disaster Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, China
| | - Dan Pu
- Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Xiao-Rong Chen
- Department of Abdominal Oncology, Cancer Center, West China Hospital of Sichuan University, Chengdu, China
| | - Chun-Hong Li
- Department of Oncology, Suining Central Hospital, Suining, China
| | - Li Jiang
- Department of Abdominal Oncology, Sichuan Cancer Hospital, Chengdu, China
| | - Yan Wang
- Department of Oncology, The First People's Hospital of Long Quan Yi District, Chengdu, China
| | - Qiu Li
- Department of Abdominal Oncology, Cancer Center, West China Hospital of Sichuan University, Chengdu, China
| | - Yu Yang
- Department of Abdominal Oncology, Cancer Center, West China Hospital of Sichuan University, Chengdu, China
| | - Hong-Feng Gou
- Department of Abdominal Oncology, Cancer Center, West China Hospital of Sichuan University, Chengdu, China
| | - Feng Bi
- Department of Abdominal Oncology, Cancer Center, West China Hospital of Sichuan University, Chengdu, China
| | - Ji-Yan Liu
- Department of Biotherapy, Cancer Center, West China Hospital of Sichuan University, Chengdu, China; Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, China.
| | - Ye Chen
- Department of Abdominal Oncology, Cancer Center, West China Hospital of Sichuan University, Chengdu, China.
| | - Meng Qiu
- Department of Abdominal Oncology, Cancer Center, West China Hospital of Sichuan University, Chengdu, China.
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Risk stratification of LI-RADS M and LI-RADS 4/5 combined hepatocellular cholangiocarcinoma: prognostic values of MR imaging features and clinicopathological factors. Eur Radiol 2022; 32:5166-5178. [PMID: 35316365 DOI: 10.1007/s00330-022-08691-w] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Revised: 02/17/2022] [Accepted: 02/24/2022] [Indexed: 12/17/2022]
Abstract
OBJECTIVES To investigate the role of clinicopathological factors and MR imaging factors in risk stratification of combined hepatocellular cholangiocarcinoma (cHCC-CCA) patients who were classified as LR-M and LR-4/5. METHODS We retrospectively identified consecutive patients who were confirmed as cHCC-CCA after surgical surgery in our institution from June 2015 to November 2020. Two radiologists evaluated the preoperative MR imaging features independently, and each lesion was assigned with a LI-RADS category. Preoperative clinical data were also collected. Multivariate Cox proportional hazards model was applied to separately identify the independent factors correlated with the recurrence of cHCC-CCAs in LR-M and LR-4/5. Risk stratifications were conducted separately in LR-M and LR-4/5. Recurrence-free survival (RFS) rates and overall survival (OS) rates were analyzed by using the Kaplan-Meier survival curves and log-rank test. RESULTS A total of 131 patients with single primary lesion which met the 2019 WHO classification criteria were finally included. Corona enhancement, delayed central enhancement, and microvascular invasion (MVI) were identified as predictors of RFS in LR-M. Mosaic architecture, CA19-9, and MVI were independently associated with RFS in LR-4/5. Based on the number of these independent predictors, patients were stratified into favorable-outcome groups (LR-ML subgroup and LR-4/5L subgroup) and dismal-outcome groups (LR-MH subgroup and LR-4/5H subgroup). The corresponding median RFS for LR-ML, LR-MH, LR-5L, and LR-5H were 25.6 months, 8.2 months, 51.7 months, and 18.1 months. CONCLUSION Our study explored the prognostic values of imaging and clinicopathological factors for LR-M and LR-4/5 cHCC-CCA patients, and different survival outcomes were observed among four subgroups after conducting risk stratifications. KEY POINTS • Corona enhancement, delayed central enhancement, and MVI were identified as predictors of RFS in cHCC-CCAs which were classified into LR-M. Mosaic architecture, CA19-9, and MVI were independently associated with RFS in cHCC-CCAs which were classified into LR-4/5. • Based on the identified risk factors, LR-M and LR-4/5 cHCC-CCA patients could be stratified into two subgroups respectively, with significantly different RFS and OS. • cHCC-CCA patients from LR-M did not always have worse RFS and OS than those from LR-4/5 in some cases.
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21
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Wu Y, Liu H, Zeng J, Chen Y, Fang G, Zhang J, Zhou W, Zeng Y, Liu J. Development and validation of nomogram to predict very early recurrence of combined hepatocellular-cholangiocarcinoma after hepatic resection: a multi-institutional study. World J Surg Oncol 2022; 20:60. [PMID: 35227269 PMCID: PMC8883704 DOI: 10.1186/s12957-022-02536-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Accepted: 02/18/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND AND OBJECTIVES Combined hepatocellular cholangiocarcinoma (cHCC) has a high incidence of early recurrence. The objective of this study is to construct a model predicting very early recurrence (VER) (i.e., recurrence within 6 months after surgery) of cHCC. METHODS One hundred thirty-one consecutive patients from Eastern Hepatobiliary Surgery Hospital served as a development cohort to construct a nomogram predicting VER by using multi-variable logistic regression analysis. The model was internally and externally validated in a validation cohort of 90 patients from Mengchao Hepatobiliary Hospital using the C concordance statistic, calibration analysis, and decision curve analysis (DCA). RESULTS The VER nomogram contains microvascular invasion (MiVI), macrovascular invasion (MaVI), and CA19-9 > 25 mAU/mL. The model shows good discrimination with C-indexes of 0.77 (95% CI: 0.69-0.85) and 0.76 (95% CI: 0.66-0.86) in the development cohort and validation cohort respectively. Decision curve analysis demonstrated that the model is clinically useful and the calibration of our model was favorable. Our model stratified patients into two different risk groups, which exhibited significantly different VER. CONCLUSIONS Our model demonstrated favorable performance in predicting VER in cHCC patients.
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Affiliation(s)
- Yijun Wu
- Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, People's Republic of China
| | - Hongzhi Liu
- Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, People's Republic of China
| | - Jianxing Zeng
- Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, People's Republic of China
| | - Yifan Chen
- Shengli Clinical Medical College of Fujian Medical University, Fuzhoum, People's Republic of China
| | - Guoxu Fang
- Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, People's Republic of China
| | - Jinyu Zhang
- Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, People's Republic of China
| | - Weiping Zhou
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, People's Republic of China
| | - Yongyi Zeng
- Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, People's Republic of China.
| | - Jingfeng Liu
- Fujian Medical University Cancer Hospital & Fujian Cancer Hospital, No. 420, Fuma Road, Fuzhou, 350014, Fujian, People's Republic of China.
- The Big Data Institute of Southeast Hepatobiliary Health Information, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, People's Republic of China.
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Hou GM, Jiang C, Du JP, Yuan KF. Sarcopenia predicts an adverse prognosis in patients with combined hepatocellular carcinoma and cholangiocarcinoma after surgery. Cancer Med 2021; 11:317-331. [PMID: 34866356 PMCID: PMC8729053 DOI: 10.1002/cam4.4448] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2021] [Revised: 11/05/2021] [Accepted: 11/08/2021] [Indexed: 02/05/2023] Open
Abstract
Background The prognostic value of sarcopenia in combined hepatocellular carcinoma and cholangiocarcinoma (cHCC‐CC) patients after surgery has not been evaluated, while the efficacy of the available tumor stage for cHCC‐CC remains controversial. Methods All consecutive cHCC‐CC patients after surgery were retrieved. The patients were stratified by the sex‐specific medians of the psoas muscle index into groups with or without sarcopenia. Prognosis was analyzed using the Kaplan–Meier (K–M) method, and the K–M curves were adjusted by inverse probability weighting (IPW). A nomogram based on Cox regression analysis was established and further compared with primary liver cancer (PLC) stages by internal validation based on bootstrap resampling and k‐fold cross‐validation. Results A total of 153 patients were stratified into sarcopenia and non‐sarcopenia groups. The sarcopenia group revealed statistically worse overall survival (OS) and disease‐free survival (DFS) using the K–M method and K–M curves adjusted by IPW. Multivariate Cox regression analyses suggested sarcopenia as an independent risk factor for OS (HR = 1.55; p = 0.040) and DFS (HR = 1.55; p = 0.019). Subgroup analysis based on baseline variables showed sarcopenia as a stable risk factor for the prognosis. Our nomogram outperformed PLC stages in prognostic prediction, as evidenced by the best c‐index, area under the curve, and positive improvement of the net reclassification index and integrated discrimination improvement. A fivefold cross‐validation revealed consistent results. Decision curve analysis revealed higher net benefits of the nomogram than PLC stages. Conclusions Sarcopenia is an independent and stable risk factor for the prognosis of cHCC‐CC patients after surgery. Our nomogram might aid high‐risk patient identification and clinical decisions.
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Affiliation(s)
- Gui-Min Hou
- Department of Liver Surgery & Liver Transplantation, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
| | - Chuang Jiang
- Department of Liver Surgery & Liver Transplantation, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
| | - Jin-Peng Du
- Department of Liver Surgery & Liver Transplantation, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
| | - Ke-Fei Yuan
- Department of Liver Surgery & Liver Transplantation, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
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23
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Tang YY, Zhao YN, Zhang T, Chen ZY, Ma XL. Comprehensive radiomics nomogram for predicting survival of patients with combined hepatocellular carcinoma and cholangiocarcinoma. World J Gastroenterol 2021; 27:7173-7189. [PMID: 34887636 PMCID: PMC8613648 DOI: 10.3748/wjg.v27.i41.7173] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2021] [Revised: 06/26/2021] [Accepted: 09/03/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Combined hepatocellular carcinoma (HCC) and cholangiocarcinoma (cHCC-CCA) is defined as a single nodule showing differentiation into HCC and intrahepatic cholangiocarcinoma and has a poor prognosis. AIM To develop a radiomics nomogram for predicting post-resection survival of patients with cHCC-CCA. METHODS Patients with pathologically diagnosed cHCC-CCA were randomly divided into training and validation sets. Radiomics features were extracted from portal venous phase computed tomography (CT) images using the least absolute shrinkage and selection operator Cox regression and random forest analysis. A nomogram integrating the radiomics score and clinical factors was developed using univariate analysis and multivariate Cox regression. Nomogram performance was assessed in terms of the C-index as well as calibration, decision, and survival curves. RESULTS CT and clinical data of 118 patients were included in the study. The radiomics score, vascular invasion, anatomical resection, total bilirubin level, and satellite lesions were found to be independent predictors of overall survival (OS) and were therefore included in an integrative nomogram. The nomogram was more strongly associated with OS (hazard ratio: 8.155, 95% confidence interval: 4.498-14.785, P < 0.001) than a model based on the radiomics score or only clinical factors. The area under the curve values for 1-year and 3-year OS in the training set were 0.878 and 0.875, respectively. Patients stratified as being at high risk of poor prognosis showed a significantly shorter median OS than those stratified as being at low risk (6.1 vs 81.6 mo, P < 0.001). CONCLUSION This nomogram may predict survival of cHCC-CCA patients after hepatectomy and therefore help identify those more likely to benefit from surgery.
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Affiliation(s)
- You-Yin Tang
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Yu-Nuo Zhao
- Department of Biotherapy, West China Hospital and State Key Laboratory of Biotherapy, Sichuan University, West China Hospital, Chengdu 610041, Sichuan Province, China
| | - Tao Zhang
- West China School of Medicine of Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Zhe-Yu Chen
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Xue-Lei Ma
- Department of Biotherapy, West China Hospital and State Key Laboratory of Biotherapy, Sichuan University, West China Hospital, Chengdu 610041, Sichuan Province, China
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24
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Zhou C, Ni X, Lu X, Wang Y, Qian X, Yang C, Zeng M. MR Features Based on LI-RADS Ver. 2018 Correlated with Cytokeratin 19 Expression in Combined Hepatocellular Carcinoma-Cholangiocarcinoma. J Hepatocell Carcinoma 2021; 8:975-983. [PMID: 34458204 PMCID: PMC8387586 DOI: 10.2147/jhc.s325686] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2021] [Accepted: 08/12/2021] [Indexed: 12/14/2022] Open
Abstract
Purpose To investigate the significance of MR features based on the Liver Imaging Reporting and Data System (LI-RADS ver. 2018) for identifying the expression of cytokeratin 19 (CK-19) in patients with combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CCA) before surgery. Patients and Methods The study enrolled 174 patients pathologically confirmed to have cHCC-CCA according to the 2019 WHO classification. The preoperative MR imaging features and clinicopathological findings were retrospectively evaluated and compared between the CK-19-positive and CK-19-negative cHCC-CCA groups. Results One hundred seventy-four patients (mean age, males vs females: 56.6 ± 10.0 years vs 54.7 ± 14.2 years) were evaluated. The presence of mosaic architecture, targetoid appearance, cholangiectasis, hepatic capsule retraction, and corona enhancement was significantly higher in the CK-19-positive group (all p < 0.05), while nonrim arterial phase hyperenhancement (APHE) was more common in the CK-19-negative group (p = 0.04). The univariate analysis showed that hepatitis B virus infection, CEA > 5 ng/mL, tumor size, nonrim APHE, mosaic architecture, targetoid appearance, cholangiectasis, hepatic capsule retraction, and corona enhancement were significant risk factors for CK-19-positive cHCC-CCA (all p < 0.05). Unfortunately, the multivariate analysis revealed that only corona enhancement (OR = 2.359, p = 0.03) was an independent risk factor associated with CK-19-positive cHCC-CCA. Conclusion Corona enhancement is significantly correlated with CK-19 positivity in patients with cHCC-CCA.
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Affiliation(s)
- Changwu Zhou
- Shanghai Institute of Medical Imaging, Shanghai, People's Republic of China.,Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
| | - Xiaoyan Ni
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
| | - Xin Lu
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
| | - Yi Wang
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
| | - Xianling Qian
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
| | - Chun Yang
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
| | - Mengsu Zeng
- Shanghai Institute of Medical Imaging, Shanghai, People's Republic of China.,Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
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Fragkou N, Sideras L, Panas P, Emmanouilides C, Sinakos E. Update on the association of hepatitis B with intrahepatic cholangiocarcinoma: Is there new evidence? World J Gastroenterol 2021; 27:4252-4275. [PMID: 34366604 PMCID: PMC8316913 DOI: 10.3748/wjg.v27.i27.4252] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 04/12/2021] [Accepted: 06/18/2021] [Indexed: 02/06/2023] Open
Abstract
Intrahepatic cholangiocarcinoma (iCCA) is a subgroup of cholangiocarcinoma that accounts for about 10%-20% of the total cases. Infection with hepatitis B virus (HBV) is one of the most important predisposing factors leading to the formation of iCCA. It has been recently estimated based on abundant epidemiological data that the association between HBV infection and iCCA is strong with an odds ratio of about 4.5. The HBV-associated mechanisms that lead to iCCA are under intense investigation. The diagnosis of iCCA in the context of chronic liver disease is challenging and often requires histological confirmation to distinguish from hepatocellular carcinoma. It is currently unclear whether antiviral treatment for HBV can decrease the incidence of iCCA. In terms of management, surgical resection remains the mainstay of treatment. There is a need for effective treatment modalities beyond resection in both first- and second-line treatment. In this review, we summarize the epidemiological evidence that links the two entities, discuss the pathogenesis of HBV-associated iCCA, and present the available data on the diagnosis and management of this cancer.
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Affiliation(s)
- Nikolaos Fragkou
- Fourth Department of Internal Medicine, Aristotle University of Thessaloniki, Thessaloniki 54642, Greece
| | - Lazaros Sideras
- Fourth Department of Internal Medicine, Aristotle University of Thessaloniki, Thessaloniki 54642, Greece
| | - Panteleimon Panas
- Fourth Department of Internal Medicine, Aristotle University of Thessaloniki, Thessaloniki 54642, Greece
| | | | - Emmanouil Sinakos
- Fourth Department of Internal Medicine, Aristotle University of Thessaloniki, Thessaloniki 54642, Greece
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26
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Zhou C, Wang Y, Ma L, Qian X, Yang C, Zeng M. Combined hepatocellular carcinoma-cholangiocarcinoma: MRI features correlated with tumor biomarkers and prognosis. Eur Radiol 2021; 32:78-88. [PMID: 34279688 DOI: 10.1007/s00330-021-08188-y] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2021] [Revised: 03/23/2021] [Accepted: 03/26/2021] [Indexed: 10/20/2022]
Abstract
OBJECTIVES To determine how MRI features are correlated to biomarkers, and to the prognostic factors for recurrence-free survival (RFS) and overall survival (OS) in combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CCA) patients. METHODS The study enrolled 160 cHCC-CCA patients pathologically confirmed according to the 2019 WHO classification. The preoperative MRI features and clinical data were retrospectively evaluated and compared between patients grouped by AFP or CA19-9 level and with pathological findings. The RFS and OS of cHCC-CCA patients were estimated using Kaplan-Meier survival curves and compared using the log-rank test. Moreover, predictors of RFS and OS were investigated using Cox regression analyses. RESULTS One hundred and sixty patients (mean age, males vs. females: 55.7 ± 10.2 years vs. 54.9 ± 14.0 years) were evaluated. The incidence of nodule-in-nodule architecture, mosaic architecture, intratumoral hemorrhage, hepatic capsule retraction, arterial phase peritumoral enhancement, and portal vein thrombus was significantly higher in patients with AFP > 20 ng/ml (all p < 0.05). Multivariate Cox regression analysis indicated that age (HR 1.031, p = 0.03), CA19-9 > 37 U/ml (HR 1.880, p = 0.04), arterial phase peritumoral enhancement (HR 2.287, p = 0.01), and delayed enhancement (HR 0.377, p = 0.02) were independent predictors of poor RFS, while arterial phase peripheral enhancement (HR 2.391, p = 0.04) was an independent predictor of poor OS. CONCLUSIONS cHCC-CCA imaging features are complex and not correlated with AFP or CA19-9. Age, CA19-9 > 37 U/ml, arterial phase peritumoral enhancement, and delayed enhancement are independent predictors of poor RFS. Arterial phase peripheral enhancement is an independent predictor of poor OS. KEY POINTS • The imaging features of combined hepatocellular carcinoma-cholangiocarcinoma are complex and are not correlated with the alpha fetoprotein or CA19-9 levels. • Age, CA19-9 > 37 U/ml, arterial phase peritumoral enhancement, and delayed enhancement are independent predictors of poor recurrence-free survival in combined hepatocellular carcinoma-cholangiocarcinoma patients. • Arterial phase peripheral enhancement is an independent predictor of poor overall survival in patients with combined hepatocellular carcinoma-cholangiocarcinoma.
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Affiliation(s)
- Changwu Zhou
- Shanghai Institute of Medical Imaging, Shanghai, China.,Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
| | - Yi Wang
- Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
| | - Li Ma
- Shanghai Institute of Medical Imaging, Shanghai, China
| | - Xianling Qian
- Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
| | - Chun Yang
- Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China.
| | - Mengsu Zeng
- Shanghai Institute of Medical Imaging, Shanghai, China. .,Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China.
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27
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Chen PD, Chen LJ, Chang YJ, Chang YJ. Long-Term Survival of Combined Hepatocellular-Cholangiocarcinoma: A Nationwide Study. Oncologist 2021; 26:e1774-e1785. [PMID: 34213048 DOI: 10.1002/onco.13893] [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: 02/01/2021] [Accepted: 06/18/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Combined hepatocellular-cholangiocarcinoma (HCC-CC) is an aggressive primary liver cancer. However, the clinical features are not clearly understood because of limited literature and the complex nature of both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). METHODS The records of 100,754 patients with newly diagnosed liver cancer between 2004 and 2013 were obtained from the Taiwan Cancer Registry. The primary outcome measures were overall survival and local recurrence-free survival. The median follow-up time was 60 months (29-120 months). RESULTS HCC-CC tended to share some characteristics with HCC, including increased frequency of stage I cases, high individual tumor rates, and similar patterns of viral hepatitis B and hepatitis C infections. In contrast, HCC-CC showed malignant behavior similar to that of CC, as high-grade tumor cell differentiation and presentation of jaundice were predominant in HCC-CC and CC compared with HCC. Overall survival and local recurrence-free survival rates of HCC-CC were between HCC and CC rates. The mortality rate of HCC-CC was 79.2% (HCC, 77.5%; CC, 93.5%) and the local recurrence rate of HCC-CC was 65.3% (HCC, 74.6%; CC, 88.4%). Surgical treatment was an independent factor for the long-term prognosis of HCC-CC, whereas transarterial chemoembolization (TAcE) promoted survival in both surgical and nonsurgical groups. CONCLUSION Our data confirmed that, although it reflects the malignant behavior of CC, HCC-CC should mainly be characterized as a subtype of HCC. With careful selection of patients, curative resection and TAcE might benefit the survival of patients with HCC-CC. IMPLICATIONS FOR PRACTICE Combined hepatocellular-cholangiocarcinoma (HCC-CC) is a rare cancer that shares demographic characteristics, as well as survival probabilities, with both hepatocellular carcinoma and cholangiocarcinoma. It occurs frequently in patients with hepatitis B virus infection, cirrhotic liver background, and early-stage disease. Compared with 20% of initial resection rates of its counterparts, HCC-CC has higher initial resection rate (55%). Although short-term overall survival is inferior to HCC, its long-term overall survival is similar with HCC.
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Affiliation(s)
- Po-Da Chen
- Department of Surgery, National Taiwan University and Hospital, Taipei, Taiwan.,Department of Surgical Oncology, National Taiwan University Cancer Center, Taipei, Taiwan
| | - Li-Ju Chen
- University of Taipei, Taipei, Taiwan.,Department of Ophthalmology, HepingFuyou Branch, Taipei City Hospital, Taipei, Taiwan
| | - Yao-Jen Chang
- Department of Surgery, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan.,School of Medicine, Buddhist Tzu Chi University, Hualien, Taiwan
| | - Yun-Jau Chang
- Department of Surgery, National Taiwan University and Hospital, Taipei, Taiwan.,Department of General Surgery, Zhong-Xing Branch, Taipei City Hospital, Taipei, Taiwan
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Yoon J, Hwang JA, Lee S, Lee JE, Ha SY, Park YN. Clinicopathologic and MRI features of combined hepatocellular-cholangiocarcinoma in patients with or without cirrhosis. Liver Int 2021; 41:1641-1651. [PMID: 33503328 DOI: 10.1111/liv.14798] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2020] [Revised: 12/11/2020] [Accepted: 01/13/2021] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIMS Differences in combined hepatocellular-cholangiocarcinomas (cHCC-CCAs) arising in high-risk patients with or without liver cirrhosis have not been elucidated. This study aimed to compare the clinicopathologic and imaging characteristics of cHCC-CCAs in patients with or without cirrhosis and to determine the prognostic factors for recurrence-free survival (RFS) after curative resections of single cHCC-CCAs. METHODS This retrospective study included 113 patients with surgically resected single cHCC-CCAs who underwent preoperative magnetic resonance imaging from January 2008 to December 2019 at two tertiary referral centres. Clinical, pathologic and imaging features of tumours were compared in high-risk patients with or without cirrhosis. Imaging features were assessed using the Liver Imaging Reporting and Data System (LI-RADS) version 2018. RFS and associated factors were evaluated using Cox proportional hazards regression analysis, Kaplan-Meier analysis and log-rank test. RESULTS cHCC-CCAs arising from cirrhotic livers had a smaller mean tumour size (2.9 cm vs. 4.5 cm; P < .001) and were more frequently categorized as LR-5 or 4 (41.2% vs. 20.0%; P = .024) than those arising from non-cirrhotic livers. In multivariable analysis, a tumour size of > 3 cm (hazard ratio [HR], 2.081; 95% confidence interval [CI], 1.180-3.668; P = .011) and the LR-M category (HR, 2.302; 95% CI, 1.198-4.424; P = .012) were independent predictors associated with worse RFS. CONCLUSIONS The tumour size and distribution of LI-RADS categories of cHCC-CCAs differed in high-risk patients with or without cirrhosis. And LR-M category was a worse prognosis predictor after curative resections than LR-5 or 4 category.
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Affiliation(s)
- Jongjin Yoon
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jeong A Hwang
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Sunyoung Lee
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Ji E Lee
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.,Department of Radiology, Soonchunhyang University College of Medicine, Bucheon Hospital, Bucheon, Republic of Korea
| | - Sang Y Ha
- Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Young N Park
- Department of Pathology, BK21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea
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Panayotova G, Lunsford KE, Latt NL, Paterno F, Guarrera JV, Pyrsopoulos N. Expanding indications for liver transplantation in the era of liver transplant oncology. World J Gastrointest Surg 2021; 13:392-405. [PMID: 34122730 PMCID: PMC8167850 DOI: 10.4240/wjgs.v13.i5.392] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Revised: 02/23/2021] [Accepted: 05/07/2021] [Indexed: 02/06/2023] Open
Abstract
Despite numerous advances and emerging data, liver transplantation in the setting of gastrointestinal malignancies remains controversial outside of certain accepted indications. In an era of persistent organ shortage and increasing organ demand, allocation of liver grafts must be considered carefully. While hepatocellular carcinoma and hilar cholangiocarcinoma have become accepted indications for transplantation, tumor size and standardized multi-disciplinary treatment protocols are necessary to ensure optimal patient outcomes. As more studies seeking to expand the oncologic indications for liver transplantation are emerging, it is becoming increasingly clear that tumor biology and response to therapy are key factors for optimal oncologic outcomes. In addition, time from diagnosis to transplantation appears to correlate with survival, as stable disease over time portends better outcomes post-operatively. Identifying aggressive disease pre-transplant remains difficult with current imaging and tissue sampling techniques. While tumor size and stage are important prognostic predictors for most malignancies, patient and tumor selection protocols are necessary. As the fields of medical and surgical oncology continue to evolve, it is clear that a protocolized interdisciplinary treatment approach is necessary for combatting any cancer effectively. Disease stability over time and response to neoadjuvant therapy may be the best predictors for successful patient outcomes and can be easily incorporated in our treatment paradigms. Current data evaluating liver transplantation for expanded oncologic indications such as: expanded criteria hepatocellular carcinoma, intrahepatic cholangiocarcinoma, mixed tumors, and liver limited metastatic colorectal carcinomas, incorporate multi-modal therapies and evaluation of tumor treatment response. While further investigation is necessary, initial results suggest there is an expanded role for transplant surgery in malignancy in a new era of liver transplant oncology.
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Affiliation(s)
- Guergana Panayotova
- Division of Transplant and Hepatobiliary Surgery, Department of Surgery, Rutgers New Jersey Medical School, Newark, NJ 07103, United States
| | - Keri E Lunsford
- Division of Transplant and Hepatobiliary Surgery, Department of Surgery, Rutgers New Jersey Medical School, Newark, NJ 07103, United States
- Center for Immunity and Inflammation, Institute for Infectious and Inflammatory Diseases, Rutgers New Jersey Medical School, Newark, NJ 07103, United States
| | - Nyan L Latt
- Division of Gastroenterology and Hepatology, Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103, United States
| | - Flavio Paterno
- Division of Transplant and Hepatobiliary Surgery, Department of Surgery, Rutgers New Jersey Medical School, Newark, NJ 07103, United States
| | - James V Guarrera
- Division of Transplant and Hepatobiliary Surgery, Department of Surgery, Rutgers New Jersey Medical School, Newark, NJ 07103, United States
| | - Nikolaos Pyrsopoulos
- Division of Gastroenterology and Hepatology, Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103, United States
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30
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Beaufrère A, Calderaro J, Paradis V. Combined hepatocellular-cholangiocarcinoma: An update. J Hepatol 2021; 74:1212-1224. [PMID: 33545267 DOI: 10.1016/j.jhep.2021.01.035] [Citation(s) in RCA: 129] [Impact Index Per Article: 32.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2020] [Revised: 01/08/2021] [Accepted: 01/18/2021] [Indexed: 12/13/2022]
Abstract
Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a tumour that exhibits both hepatocytic and biliary differentiation. Classical risk factors for hepatocellular carcinoma (HCC) seem to also predispose patients to the development of cHCC-CCA. The pathological definition of cHCC-CCA has significantly evolved over time. The last 2019 WHO classification highlighted that the diagnosis of cHCC-CCA should be primarily based on morphology using routine stainings, with additional immunostaining used to refine the identification of subtypes. Among them, "intermediate cell carcinoma" is recognised as a specific subtype, while "cholangiolocellular carcinoma" is now considered a subtype of iCCA. Increasing molecular evidence supports the clonal nature of cHCC-CCA and parallels its biphenotypic histological appearance, with genetic alterations that are classically observed in HCC and/or iCCA. That said, the morphological diagnosis of cHCC-CCA is still challenging for radiologists and pathologists, especially on biopsy specimens. Identification of cHCC-CCA's cell of origin remains an area of active research. Its prognosis is generally worse than that of HCC, and similar to that of iCCA. Resection with lymph node dissection is unfortunately the only curative option for patients with cHCC-CCA. Thus, there remains an urgent need to develop specific therapeutic strategies for this unique clinical entity.
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Affiliation(s)
- Aurélie Beaufrère
- Université de Paris, INSERM U1149, Hôpital Beaujon, Clichy, France; Pathology Department, Hôpital Beaujon, AP-HP, Clichy, France
| | | | - Valérie Paradis
- Université de Paris, INSERM U1149, Hôpital Beaujon, Clichy, France; Pathology Department, Hôpital Beaujon, AP-HP, Clichy, France.
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31
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Hou GM, Liu HL, Wu H, Zeng Y. Prediction of Prognosis for cHCC-CC Patients After Surgery: Comparison of Tumor Marker Score Based on AFP, CEA, CA19-9, and Other Clinical Stages. Ann Surg Oncol 2021; 28:7647-7660. [PMID: 33900502 DOI: 10.1245/s10434-021-09949-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Accepted: 03/19/2021] [Indexed: 02/05/2023]
Abstract
BACKGROUND The effectiveness of clinical stage as a prognostic factor in combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) patients is controversial. PATIENTS AND METHODS Medical records of all pathologically confirmed cHCC-CC patients from 2000 to 2017 at West China Hospital were retrieved. Tumor marker score (TMS) was determined from optimal AFP, CEA, and CA19-9 cutoff values. Interaction and subgroup analysis were conducted according to potential confounders. Prognostic value of TMS and other prognostic models were evaluated by Kaplan-Meier (K-M) analysis, c-index, and time-dependent receiver operating curves (td-ROC). RESULTS Optimal cutoff values for preoperative AFP, CEA, and CA19-9 were 10.76 ng/mL, 5.24 ng/mL, and 31.54 U/mL, respectively. Among 128 patients, 24, 58, and 46 were classified into TMS 0, TMS 1, and TMS ≥ 2, respectively. TMS could stratify our series into groups of statistically different prognosis. Subgroup analysis according to potential confounders and test for interactions showed that TMS 1 and TMS ≥ 2 were stable risk factors relative to TMS 0. Univariate (HR: TMS1 = 2.30, p = 0.014; TMS ≥ 2 = 5.1, p < 0.001) and multivariate Cox regression analyses (HR: TMS1 = 1.72, p = 0.124; TMS ≥ 2 = 4.15, p < 0.001) identified TMS as an independent prognostic risk factor. TMS had good discrimination (c-index 0.666, 95% CI 0.619-0.714), and calibration plots revealed favorable consistency. Area under the curve (AUC) value of td-ROC for TMS and integrated AUC was higher than for other clinical stages at any month within 5 years postoperation. CONCLUSION TMS exhibited optimal prognostic value over other widely used clinical stages for cHCC-CC after surgery and may guide clinicians in prognostic prediction.
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Affiliation(s)
- Gui-Min Hou
- Department of Liver Surgery and Liver Transplantation Center, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.,Laboratory of Liver Surgery, West China Hospital, Sichuan University, Chengdu, China.,Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan Province, China
| | - Hai-Ling Liu
- Department of Liver Surgery and Liver Transplantation Center, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.,Laboratory of Liver Surgery, West China Hospital, Sichuan University, Chengdu, China.,Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan Province, China
| | - Hong Wu
- Department of Liver Surgery and Liver Transplantation Center, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.,Laboratory of Liver Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Yong Zeng
- Department of Liver Surgery and Liver Transplantation Center, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China. .,Laboratory of Liver Surgery, West China Hospital, Sichuan University, Chengdu, China. .,Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan Province, China.
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32
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Tang Y, Wang L, Teng F, Zhang T, Zhao Y, Chen Z. The clinical characteristics and prognostic factors of combined Hepatocellular Carcinoma and Cholangiocarcinoma, Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma after Surgical Resection: A propensity score matching analysis. Int J Med Sci 2021; 18:187-198. [PMID: 33390787 PMCID: PMC7738961 DOI: 10.7150/ijms.50883] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Accepted: 10/13/2020] [Indexed: 02/05/2023] Open
Abstract
Background: Clinical characteristics and prognosis among combined hepatocellular carcinoma (HCC) and cholangiocarcinoma (cHCC-CC) with HCC and intrahepatic cholangiocarcinoma (ICC) were inconsistent in previous studies. The aim of this study was to compare postoperative prognosis among cHCC-CC, HCC and ICC, and investigated the prognostic risk factor of cHCC-CC after surgical resection. Methods: A total of 1041 eligible patients with pathological diagnosis of cHCC-CC (n=135), HCC (n=698) and ICC (n=208) were enrolled in this study. Univariate and multivariate Cox analysis were applied for assessing important risk factors. cHCC-CC were further 1:1 matched with HCC and ICC on important clinical risk factors. Survival curves of matched and unmatched cohorts were depicted by Kaplan-Meier method with log-rank test. Results: Patients with cHCC-CC had similar rate of sex, age and cirrhosis with HCC (p<0.05) and comparable incidence of hepatitis B or C with ICC (p=0.197). Patients of cHCC-CC had intermediate prognosis between HCC and ICC, with median overall survival (OS) time of cHCC-CC, HCC and ICC of 20.5 months, 35.7 months and 11.6 months (p<0.001). In matched cohorts, the OS of cHCC-CC were worse than HCC (p<0.001) but comparable with ICC (p=0.06), while the disease-free survival (DFS) of cHCC-CC was worse than HCC but better than ICC (p<0.05). And lymph node infiltration and postoperative transarterial chemoembolization (TACE) were independent risk factors of cHCC-CC associated with prognosis. Conclusion: The long term survival of cHCC-CC was worse than HCC but comparable with ICC when matched on albumin level, tumor size, lymph node infiltration, tumor stage and margin. Presence of lymph node infiltration and no postoperative TACE were associated with poor prognosis of cHCC-CC.
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Affiliation(s)
- Youyin Tang
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, No. 37 GuoXue Alley, Chengdu 610041, P.R. China
| | - Lingyan Wang
- Department of Obstetrics and Gynecology Nursing, Key Laboratory of Birth Defects and Related Disease of Women and Children, West China Second University Hospital, Sichuan University, No. 20 South Renmin Road, Chengdu 610041, P.R. China
| | - Fei Teng
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, No. 37 GuoXue Alley, Chengdu 610041, P.R. China
| | - Tao Zhang
- Department of Biotherapy, West China Hospital and State Key Laboratory of Biotherapy, Sichuan University, No. 37 GuoXue Alley, Chengdu 610041, P.R. China
| | - Yunuo Zhao
- Department of Biotherapy, West China Hospital and State Key Laboratory of Biotherapy, Sichuan University, No. 37 GuoXue Alley, Chengdu 610041, P.R. China
| | - Zheyu Chen
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, No. 37 GuoXue Alley, Chengdu 610041, P.R. China
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33
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Schizas D, Mastoraki A, Routsi E, Papapanou M, Tsapralis D, Vassiliu P, Toutouzas K, Felekouras E. Combined hepatocellular-cholangiocarcinoma: An update on epidemiology, classification, diagnosis and management. Hepatobiliary Pancreat Dis Int 2020; 19:515-523. [PMID: 32753331 DOI: 10.1016/j.hbpd.2020.07.004] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Accepted: 07/17/2020] [Indexed: 02/08/2023]
Abstract
BACKGROUND Combined hepatocellular-cholangiocarcinoma (CHC) is a rare subtype of primary hepatic malignancies, with variably reported incidence between 0.4%-14.2% of primary liver cancer cases. This study aimed to systematically review the epidemiological, clinicopathological, diagnostic and therapeutic data for this rare entity. DATA SOURCES We reviewed the literature of diagnostic approach of CHC with special reference to its clinical, molecular and histopathological characteristics. Additional analysis of the recent literature in order to evaluate the results of surgical and systemic treatment of this entity has been accomplished. RESULTS The median age at CHC's diagnosis appears to be between 50 and 75 years. Evaluation of tumor markers [alpha fetoprotein (AFP), carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA)] along with imaging patterns provides better opportunities for CHC's preoperative diagnosis. Reported clinicopathologic prognostic parameters possibly correlated with increased tumor recurrence and grimmer survival odds include advanced age, tumor size, nodal and distal metastases, vascular and regional organ invasion, multifocality, decreased capsule formation, stem-cell features verification and increased GGT as well as CA19-9 and CEA levels. In case of inoperable or recurrent disease, combinations of cholangiocarcinoma-directed systemic agents display superior results over sorafenib. Liver-directed methods, such as transarterial chemoembolization (TACE), percutaneous ethanol injection (PEI), hepatic arterial infusion chemotherapy (HAIC), radioembolization and ablative therapies, demonstrate inferior efficacy than in cases of hepatocellular carcinoma (HCC) due to CHC's common hypovascularity. CONCLUSIONS CHC demonstrates an overlapping clinical and biological pattern between its malignant ingredients. Natural history of the disease seems to be determined by the predominant tumor element. Gold standard for diagnosis is histology of surgical specimens. Regarding therapeutic interventions, major hepatectomy is acknowledged as the cornerstone of treatment whereas minor hepatectomy and liver transplantation may be applied in patients with advanced cirrhosis. Despite all therapeutic attempts, prognosis of CHC remains dismal.
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Affiliation(s)
- Dimitrios Schizas
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
| | - Aikaterini Mastoraki
- Fourth Department of Surgery, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece.
| | - Eleni Routsi
- Fourth Department of Surgery, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece
| | - Michail Papapanou
- Fourth Department of Surgery, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece
| | | | - Pantelis Vassiliu
- Fourth Department of Surgery, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece
| | - Konstantinos Toutouzas
- First Department of Propaedeutic Surgery, National and Kapodistrian University of Athens, Hippocration Hospital, Athens, Greece
| | - Evangelos Felekouras
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
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Raevskaya O, Appelman H, Razumilava N. A Contemporary Approach to Diagnosis and Treatment of Combined Hepatocellular-Cholangiocarcinoma. ACTA ACUST UNITED AC 2020; 19:478-485. [PMID: 33415066 DOI: 10.1007/s11901-020-00556-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Purpose of review To provide updates on terminology, epidemiology, diagnosis, and treatment of combined hepatocellular-cholangiocarcinoma (cHCC-CCA). Recent findings cHCC-CCAs are tumors that in the same nodule contain a variable degree of HCC and CCA components with a transition zone. cHCC-CCAs develop in cirrhotic and non-cirrhotic livers like and is associated with poor outcomes. Mutations in TP53, TERT promoter, and ARID1A are the most common genetic aberrations in cHCC-CCA. Fusion gene PTMS-AP1G1 is unique for cHCC-CCA. A biopsy is required for diagnosis. Surgical resection remains treatment of choice, while liver transplantation for early cHCC-CCA is associated with favorable outcomes. Gemcitabine-based therapy shows benefits for advanced cHCC-CCA. Summary cHCC-CCAs are a heterogeneous group of primary liver cancers with unique biological behavior. Multicenter studies are required for a molecular analysis to inform novel therapeutic approaches, and understand epidemiology and benefits of liver transplantation, liver-directed and targeted therapies for this rare aggressive cancer.
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Affiliation(s)
- Olga Raevskaya
- Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
| | - Henry Appelman
- Department of Pathology, University of Michigan, Ann Arbor, MI, USA
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Gentile D, Donadon M, Di Tommaso L, Samà L, Franchi E, Costa G, Lleo A, Torzilli G. Is the outcome after hepatectomy for transitional hepatocholangiocarcinoma different from that of hepatocellular carcinoma and mass-forming cholangiocarcinoma? A case-matched analysis. Updates Surg 2020; 72:671-679. [PMID: 32445033 DOI: 10.1007/s13304-020-00802-w] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2020] [Accepted: 05/13/2020] [Indexed: 02/06/2023]
Abstract
Hepatocholangiocarcinoma (HCC-CC) is a rare malignancy containing features of both hepatocellular carcinoma (HCC) and mass-forming cholangiocarcinoma (MFCCC), of which the outcome after hepatectomy remains to be clarified. The aim of this study was to analyze the characteristics and outcomes of patients with transitional HCC-CC and compare them with those of patients with HCC and MFCCC. Our prospectively maintained database was queried, and 14 transitional HCC-CC patients were identified over a total of 406 consecutive hepatic resections. A 1:1:1 match was performed with HCC and MFCCC patients operated in the same period. A total of 42 patients were matched according to tumor stage (T1-2-3, N0, M0), number of tumors, R0 resection, no 90-day mortality, and follow-up. Primary endpoints were disease-free survival (DFS) and overall survival (OS). Disease-free survival rates at 1-, 3-, and 5-year were 71.4%, 57.1%, 35.7% for transitional HCC-CC patients; 85.7%, 40.4%, 10.1% for HCC patients; 85.1%, 34.0%, 22.7% for MFCCC patients (5-year DFS: HCC-CC vs. HCC, p = 0.575; HCC-CC vs. MFCCC, p = 0.766, respectively). Similarly, OS rates at 1-, 3-, and 5-year were 92.9%, 71.4%, 64.3% for transitional HCC-CC patients; 100%, 64.3%, 41.7% for HCC patients; 100%, 54.5%, 43.6% for MFCCC patients (5-year OS: HCC-CC vs. HCC, p = 0.891; HCC-CC vs. MFCCC, p = 0.673, respectively). When accurately matched with respect to tumor burden, transitional HCC-CC patients show similar outcomes to those of HCC and MFCCC patients. Further evaluations of differences in tumor biology are necessary to better characterize the prognosis of transitional HCC-CC patients.
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Affiliation(s)
- Damiano Gentile
- Department of Hepatobiliary and General Surgery, Humanitas Clinical and Research Center-IRCCS, Rozzano, Milan, Italy
| | - Matteo Donadon
- Department of Hepatobiliary and General Surgery, Humanitas Clinical and Research Center-IRCCS, Rozzano, Milan, Italy
- Department of Biomedical Science, Humanitas University, Pieve Emanuele, Milan, Italy
| | - Luca Di Tommaso
- Department of Biomedical Science, Humanitas University, Pieve Emanuele, Milan, Italy
- Department of Pathology, Humanitas Clinical and Research Center-IRCCS, Rozzano, Milan, Italy
| | - Laura Samà
- Department of Hepatobiliary and General Surgery, Humanitas Clinical and Research Center-IRCCS, Rozzano, Milan, Italy
| | - Eloisa Franchi
- Department of Hepatobiliary and General Surgery, Humanitas Clinical and Research Center-IRCCS, Rozzano, Milan, Italy
| | - Guido Costa
- Department of Hepatobiliary and General Surgery, Humanitas Clinical and Research Center-IRCCS, Rozzano, Milan, Italy
| | - Ana Lleo
- Department of Biomedical Science, Humanitas University, Pieve Emanuele, Milan, Italy
- Department of Internal Medicine, Humanitas Clinical and Research Center-IRCCS, Rozzano, Milan, Italy
| | - Guido Torzilli
- Department of Hepatobiliary and General Surgery, Humanitas Clinical and Research Center-IRCCS, Rozzano, Milan, Italy.
- Department of Biomedical Science, Humanitas University, Pieve Emanuele, Milan, Italy.
- Division of Hepatobiliary and General Surgery, Department of Surgery, Humanitas University, Humanitas Clinical and Research Center-IRCCS, Via Manzoni, 56, 20089, Rozzano, Milano, Italy.
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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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Radiological features and outcomes of combined hepatocellular-cholangiocarcinoma in patients undergoing surgical resection. J Formos Med Assoc 2020; 119:125-133. [DOI: 10.1016/j.jfma.2019.02.012] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2018] [Revised: 02/01/2019] [Accepted: 02/23/2019] [Indexed: 12/14/2022] Open
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Song P, Midorikawa Y, Nakayama H, Higaki T, Moriguchi M, Aramaki O, Yamazaki S, Aoki M, Teramoto K, Takayama T. Patients' prognosis of intrahepatic cholangiocarcinoma and combined hepatocellular-cholangiocarcinoma after resection. Cancer Med 2019; 8:5862-5871. [PMID: 31407490 PMCID: PMC6792494 DOI: 10.1002/cam4.2495] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2019] [Revised: 07/30/2019] [Accepted: 08/01/2019] [Indexed: 12/12/2022] Open
Abstract
Combined hepatocellular-cholangiocarcinoma (cHCC-CC) and intrahepatic cholangiocarcinoma (ICC) are classified into one category, but comparison of prognosis of the two carcinomas remains controversial. The aim of the current study was to investigate surgical outcomes for patients with ICC or cHCC-CC who underwent resection in order to elucidate whether the classification of ICC and cHCC-CC is justified. Subjects were 61 patients with ICC and 29 patients with cHCC-CC who underwent liver resection from 2001 to 2017. Clinic-pathological data from the two groups were compared. Tumor number and vascular invasion were independent risk factors for recurrence-free survival (RFS) in both groups (P < .001 for both). Of note, for patients with ICC, tumor cut-off size of 5 cm showed statistical significance in median RFS (>5 cm vs ≤5 cm, 0.5 years vs 4.0 years, P = .003). For patients with cHCC-CC, tumor cut-off size of 2 cm showed statistical significance in median RFS (>2 cm vs ≤2 cm, 0.6 years vs 2.6 years, P = .038). The median RFS of patients with cHCC-CC was 0.9 years (95% confidence interval: 0.3-1.6), which was poorer than that of patients with ICC (1.3 years, 0.5-2.1) (P = .028); the rate of RFS at 5 years was 0% and 37.7% respectively. Our study supports the concept of classifying ICC and cHCC-CC into different categories because of a significant difference in RFS between the two.
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Affiliation(s)
- Peipei Song
- Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Yutaka Midorikawa
- Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Hisashi Nakayama
- Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Tokio Higaki
- Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Masamichi Moriguchi
- Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Osamu Aramaki
- Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Shintaro Yamazaki
- Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Masaru Aoki
- Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Kenichi Teramoto
- Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Tadatoshi Takayama
- Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan
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Wakizaka K, Yokoo H, Kamiyama T, Ohira M, Kato K, Fujii Y, Sugiyama K, Okada N, Ohata T, Nagatsu A, Shimada S, Orimo T, Kamachi H, Taketomi A. Clinical and pathological features of combined hepatocellular-cholangiocarcinoma compared with other liver cancers. J Gastroenterol Hepatol 2019; 34:1074-1080. [PMID: 30462849 DOI: 10.1111/jgh.14547] [Citation(s) in RCA: 62] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2018] [Revised: 11/09/2018] [Accepted: 11/11/2018] [Indexed: 02/05/2023]
Abstract
BACKGROUND AND AIM Combined hepatocellular-cholangiocarcinoma (CHC) is a primary liver cancer containing both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) elements. Its reported clinicopathological features and prognoses have varied because of its low prevalence. This study aimed to clarify these aspects of CHC. METHODS We enrolled 28 patients with CHC, 1050 with HCC, and 100 with ICC and compared the clinicopathological characteristics and prognosis of CHC with HCC and ICC. We also analyzed prognostic factors, recurrence patterns, and management in CHC patients. RESULTS The incidences of hepatitis B virus and high α-fetoprotein and protein induced by vitamin K absence or antagonists-II levels were significantly higher among CHC compared with ICC patients. Multiple tumors were more frequent in CHC compared with the other groups, while vascular invasion and lymph node metastasis were more frequent in the CHC than the HCC group. The 5-year overall survival and disease-free survival rates for CHC were 25.1% and 22.6%, respectively. Overall survival was significantly lower than for HCC (P < 0.001) but not ICC (P = 0.152), while disease-free survival was significantly lower than for HCC and ICC (P = 0.008 and P = 0.005, respectively). Multivariate analysis identified carcinoembryonic antigen levels and tumor size as independent predictors in patients with CHC. CONCLUSIONS The clinical features of CHC, including sex, hepatitis B virus infection, α-fetoprotein, and protein induced by vitamin K absence or antagonists-II levels, were similar to HCC, while its prognosis and pathological features, including vascular invasion and lymph node metastasis, were similar to ICC. Carcinoembryonic antigen levels and tumor size were independent prognostic factors in patients with CHC.
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Affiliation(s)
- Kazuki Wakizaka
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Hideki Yokoo
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Toshiya Kamiyama
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Masafumi Ohira
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Koichi Kato
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Yuki Fujii
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Ko Sugiyama
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Naoki Okada
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Takanori Ohata
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Akihisa Nagatsu
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Shingo Shimada
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Tatsuya Orimo
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Hirofumi Kamachi
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Akinobu Taketomi
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
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Competing risk analyses of overall survival and cancer-specific survival in patients with combined hepatocellular cholangiocarcinoma after surgery. BMC Cancer 2019; 19:178. [PMID: 30813928 PMCID: PMC6391817 DOI: 10.1186/s12885-019-5398-6] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2018] [Accepted: 02/20/2019] [Indexed: 12/15/2022] Open
Abstract
Background Our objective was to identify risk factors affecting overall survival (OS) and cancer-specific survival (CSS) and build nomograms to predict survival based on a large population-based cohort. Methods Two hundred and thirty patients diagnosed with CHCC between 2004 and 2015 were retrospectively extracted from the Surveillance, Epidemiology, and End Results (SEER) database as a training cohort. In addition, Ninety-nine patients diagnosed with CHCC between 2000 and 2017 were retrospectively extracted from Sun Yat-Sen University Cancer Center (SYSUCC) as an external validation. Nomograms for predicting probability of OS and CSS were established. Performance of the nomograms was measured by concordance index (C-index) and the area under receiver operating characteristic (ROC) curve (AUC). Results In training cohort, the 1-, 2 and 3-year OS were 67.7, 46.8 and 37.9%, and the 1-, 2 and 3-year CSS were 73.1, 52.0 and 43.0%, respectively. The established nomograms were well calibrated in both training and validation cohort, with concordance indexes (C-index) of 0.652 and 0.659, respectively for OS prediction; 0.706 and 0.763, respectively for CSS prediction. Nomograms also displayed better discriminatory compared with 8th edition tumor-node-metastasis (TNM) stage system for predicting OS and CSS. Conclusion We constructed nomograms to predict OS and CSS based on a relatively large cohort. The established nomograms were well validated and could serve to improve predictions of survival risks and guide management of patients with CHCC after surgery.
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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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Lunsford KE, Court C, Seok Lee Y, Lu DS, Naini BV, Harlander-Locke MP, Busuttil RW, Agopian VG. Propensity-Matched Analysis of Patients with Mixed Hepatocellular-Cholangiocarcinoma and Hepatocellular Carcinoma Undergoing Liver Transplantation. Liver Transpl 2018; 24:1384-1397. [PMID: 29573187 DOI: 10.1002/lt.25058] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2017] [Revised: 04/30/2018] [Accepted: 03/13/2018] [Indexed: 12/13/2022]
Abstract
Mixed hepatocellular-cholangiocarcinomas (HCC-CCAs) are rare tumors with both hepatocellular and biliary differentiation. While liver transplantation (LT) is the gold standard treatment for patients with unresectable hepatocellular carcinoma (HCC), it is contraindicated in known HCC-CCA because of concerns of poor prognosis. We sought to compare posttransplant oncologic outcomes for HCC-CCA and a matched cohort of HCC LT recipients. A retrospective, single-center analysis (1984-2015) identified 12 patients with mixed HCC-CCA who were matched 1:3 to patients with HCC on both pretransplant (radiologic diameter and alpha-fetoprotein) and explant (pathologic diameter, grade/differentiation, and vascular invasion) tumor characteristics. Compared with HCC patients matched on pretransplant characteristics (n = 36), HCC-CCA had higher explant tumor grade, more poorly differentiated tumors, but similar T stage and vascular invasion. HCC-CCA recipients trended toward inferior recurrence-free survival at 5 years (28% versus 61%; P = 0.12) and greater recurrence (HCC-CCA: 50%, median time to recurrence 297 days versus HCC: 22%, median time to recurrence 347 days; P = 0.07). However, when matched to a separate HCC cohort with similar explant pathology, HCC-CCA had similar 5-year recurrence-free survival (42% versus 44%; P = 0.45) and posttransplant recurrence (50% versus 27%; P = 0.13). All 6 HCC-CCA recurrences occurred with poorly differentiated tumors (median survival 21.3 months), without a single recurrence in 5 of the 12 HCC-CCA patients with well-moderately differentiated tumors (median survival 60.2 months). Mixed HCC-CCA tumors are more likely poorly differentiated tumors compared with HCC with similar pretransplant characteristics. However, compared with HCC with similar pathologic characteristics, they display similar recurrence-free survival and are not inherently more aggressive tumors. Low-grade, well-moderately differentiated HCC-CCAs have excellent survival with a low risk for post-LT recurrence, and they should not be excluded from LT. Improved pretransplant identification of pathologic characteristics in HCC-CCA may allow for successful utilization of LT in this subset of patients.
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Affiliation(s)
- Keri E Lunsford
- J.C. Walter Center for Transplantation, Department of Surgery, Weill Cornell Medical College, Houston Methodist Hospital and Research Institute, Houston, TX
| | - Colin Court
- Division of Liver and Pancreas Transplantation, Departments of Surgery, David Geffen School of Medicine at University of California, Los Angeles, CA
| | - Yong Seok Lee
- Radiology, David Geffen School of Medicine at University of California, Los Angeles, CA
| | - David S Lu
- Radiology, David Geffen School of Medicine at University of California, Los Angeles, CA
| | - Bita V Naini
- Pathology, David Geffen School of Medicine at University of California, Los Angeles, CA
| | - Michael P Harlander-Locke
- Division of Liver and Pancreas Transplantation, Departments of Surgery, David Geffen School of Medicine at University of California, Los Angeles, CA
| | - Ronald W Busuttil
- Division of Liver and Pancreas Transplantation, Departments of Surgery, David Geffen School of Medicine at University of California, Los Angeles, CA
| | - Vatche G Agopian
- Division of Liver and Pancreas Transplantation, Departments of Surgery, David Geffen School of Medicine at University of California, Los Angeles, CA
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He C, Mao Y, Wang J, Song Y, Huang X, Lin X, Li S. The Predictive Value of Staging Systems and Inflammation Scores for Patients with Combined Hepatocellular Cholangiocarcinoma After Surgical Resection: a Retrospective Study. J Gastrointest Surg 2018; 22:1239-1250. [PMID: 29667093 DOI: 10.1007/s11605-018-3756-3] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2017] [Accepted: 03/21/2018] [Indexed: 01/31/2023]
Abstract
BACKGROUND Combined hepatocellular cholangiocarcinoma (cHCC-CC) is a rare form of primary liver tumor. A specific staging system for predicting survival in patients with cHCC-CC is not available. The aim of the present study was to evaluate the ability of staging systems and inflammation-based scores to predict overall survival (OS) and progression-free survival (PFS) of patients with cHCC-CC after surgical resection. METHODS The data from 99 patients with cHCC-CC after surgical resection from June 2000 and January 2017 were retrospectively collected. Patients were allocated into HCC (hepatocellular carcinoma)-dominant (IHD) group and ICC (intrahepatic cholangiocarcinoma)-dominant (IID) group based on radiological characteristics. Similarly, patients were also divided into HCC-dominant (PHD) group and ICC-dominant (PID) group based on pathological characteristics. Univariate and multivariate analyses were performed to identify variables associated with OS and PFS. The prognostic value of staging systems and inflammation-based scores were analyzed and compared using receiver operating characteristic (ROC) curves. RESULTS The 1-, 2-, and 3-year OS rates were 82.6, 66.3, and 59.6%, respectively. The 1-, 2-, and 3-year PFS rates were 52.2, 38.1, and 31.5%, respectively. Independent prognostic factors identified by multivariate analyses included HCC-TNM staging system and tumor diameter both for OS and PFS analyses. HCC-TNM staging system displayed higher area under ROC curve (AUC) values than the other staging systems or inflammation-based scores. CONCLUSIONS HCC-TNM staging system was able to adequately predict prognosis of patients with cHCC-CC after surgical resection, especially for patients with HCC-dominant characteristics in clinical practice.
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Affiliation(s)
- Chaobin He
- Department of Hepatobiliary and Pancreatic Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, Guangdong, People's Republic of China
| | - Yize Mao
- Department of Hepatobiliary and Pancreatic Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, Guangdong, People's Republic of China
| | - Jun Wang
- Department of Hepatobiliary and Pancreatic Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, Guangdong, People's Republic of China
| | - Yunda Song
- Department of Hepatobiliary and Pancreatic Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, Guangdong, People's Republic of China
| | - Xin Huang
- Department of Hepatobiliary and Pancreatic Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, Guangdong, People's Republic of China
| | - Xiaojun Lin
- Department of Hepatobiliary and Pancreatic Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, Guangdong, People's Republic of China
| | - Shengping Li
- Department of Hepatobiliary and Pancreatic Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, Guangdong, People's Republic of China.
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The effectiveness of transarterial chemoembolization in recurrent hepatocellular-cholangiocarcinoma after resection. PLoS One 2018; 13:e0198138. [PMID: 29879137 PMCID: PMC5991684 DOI: 10.1371/journal.pone.0198138] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2018] [Accepted: 05/14/2018] [Indexed: 12/13/2022] Open
Abstract
Background Combined hepatocellular-cholangiocarcinoma (cHCC-CC) can present as a hypervascular or peripherally enhancing tumor in dynamic imaging. We evaluated the effect of transarterial chemoembolization (TACE) on prognosis according to post-operative recurrence imaging patterns. Methods We retrospectively analyzed 42 cHCC-CC and 59 hepatocellular carcinoma (HCC-control) patients at the Asan Medical Center. We classified recurrent cHCC-CC according to enhancement pattern (globally enhancing: GE cHCC-CC, peripherally enhancing: PE cHCC-CC) and evaluated tumor response, time-to-local progression (TTPlocal), and overall survival (OS). Results The GE cHCC-CC group had a significantly higher best objective response rate (complete remission + partial response) than the PE cHCC-CC group (36% vs 0%, P = 0.005), and it was comparable to that of the HCC-control group (35.6%, P = 0.97). TTPlocal in the GE cHCC-CC group was significantly shorter than in the HCC-control group (6.6 vs 27.1 months, P < 0.001), and was not significantly different from that in the PE cHCC-CC group (5.3 months, P = 0.12). OS was 12.4 months, 52.8 months, and 67.5 months in the PE cHCC-CC, GE cHCC-CC, and HCC-control groups, respectively (Ps < 0.05). The adjusted hazard ratios (HRs) for TTPlocal and OS revealed an independent association with enhancement pattern of recurrent cHCC-CC (TTPlocal: HR 2.46; 95% CI 1.10–5.46; P = 0.03; OS: HR 5.97; 95% CI 2.38–14.96; P < 0.001). Conclusions The GE cHCC-CC group showed better response and prognosis after TACE than the PE cHCC-CC group, but poorer response and prognosis than the HCC-control group. Enhancement patterns at recurrence were crucially associated with tumor response and overall survival.
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He C, Mao Y, Lao X, Li S, Lin X. Neutrophil-to-lymphocyte ratio predicts overall survival of patients with combined hepatocellular cholangiocarcinoma. Oncol Lett 2018; 15:4262-4268. [PMID: 29541193 PMCID: PMC5835899 DOI: 10.3892/ol.2018.7882] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2016] [Accepted: 07/20/2017] [Indexed: 12/13/2022] Open
Abstract
The neutrophil-to-lymphocyte ratio (NLR) has been regarded as a prognostic factor in various types of cancer. The present study aimed to identify the association between NLR and combined hepatocellular cholangiocarcinoma (cHCC-CC) in patients who underwent surgical resection. The present study retrospectively reviewed 59 patients who were diagnosed with cHCC-CC and treated with surgical resection between January 2000 and October 2014 at the Department of Hepatobiliary and Pancreatic Surgery at Sun Yat-sen University Cancer Center (Guangzhou, China). The patients were divided into two groups: NLR≤2.75 and NLR>2.75. Patients with stage I and II or stage III and IV disease were classified into early- and advanced-stage groups, respectively, according to the Tumor-Node-Metastasis (TNM) staging system. Overall survival time (OS) was estimated using the Kaplan-Meier method. Univariate and multivariate Cox regression models were used to evaluate the prognostic value of NLR. The NLR value was significantly higher in the HCC advanced-stage group compared with that in the HCC early-stage group according to the TNM staging system (3.19 vs. 2.00; P=0.001). The median survival time was 83.6 months in the NLR≤2.75 group and 15 months in the NLR>2.75 group (P=0.004). Upon multivariate analysis, NLR>2.75 was an independent prognostic factor for poor cHCC-CC outcomes. Overall, the easily evaluated pre-treatment NLR may be an independent prognostic factor for patients with cHCC-CC treated by surgical resection.
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Affiliation(s)
- Chaobin He
- Department of Hepatobiliary Oncology, Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510060, P.R. China
| | - Yize Mao
- Department of Hepatobiliary Oncology, Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510060, P.R. China
| | - Xiangming Lao
- Department of Hepatobiliary Oncology, Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510060, P.R. China
| | - Shengping Li
- Department of Hepatobiliary Oncology, Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510060, P.R. China
| | - Xiaojun Lin
- Department of Hepatobiliary Oncology, Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510060, P.R. China
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Tao CY, Liu WR, Jin L, Tang Z, Tian MX, Jiang XF, Wang H, Zhou PY, Fang Y, Ding ZB, Peng YF, Dai Z, Qiu SJ, Zhou J, Fan J, Shi YH. Surgical Treatment of Combined Hepatocellular-Cholangiocarcinoma is as Effective in Elderly Patients as it is in Younger Patients: A Propensity Score Matching Analysis. J Cancer 2018; 9:1106-1112. [PMID: 29581790 PMCID: PMC5868178 DOI: 10.7150/jca.23921] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2017] [Accepted: 01/28/2018] [Indexed: 12/11/2022] Open
Abstract
Aims: To compare the long-term prognosis of younger and elderly patients with combined hepatocellular-cholangiocarcinoma (CHC) who underwent curative resection between 1993 and 2014 at our center. Methods: Two hundred and thirteen patients who underwent liver resection for CHC were enrolled in our study. The overall survival (OS) and disease-free survival (DFS) of elderly patients (age≥60, n=52) and younger patients (age<60, n=161) were compared by multivariate analysis and propensity score matching (PSM) analysis. Results: Among the 213 CHC patients, the elderly patients had a higher rate of worse Child-Pugh grade (P=0.027), abnormal serum albumin (P<0.001) and lymphoid metastases (P=0.024). The proportion of HBV-positive CHC patients (74.6%, 159/213) was much higher than that observed in healthy cohorts. Younger patients had a higher rate of hepatitis B virus (HBV) infection compared to older patients (83.9% vs 46.2%, P<0.001). OS and DFS of the elderly and younger patients before and after propensity score matching were comparable. Conclusion: Elderly and younger patients who underwent liver resection for CHC have comparable long-term OS and DFS.
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Affiliation(s)
- Chen-Yang Tao
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China
| | - Wei-Ren Liu
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China
| | - Lei Jin
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China
| | - Zheng Tang
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China
| | - Meng-Xin Tian
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China
| | - Xi-Fei Jiang
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China
| | - Han Wang
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China
| | - Pei-Yun Zhou
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China
| | - Yuan Fang
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China
| | - Zhen-Bin Ding
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China
| | - Yuan-Fei Peng
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China
| | - Zhi Dai
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China
| | - Shuang-Jian Qiu
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China
| | - Jian Zhou
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China.,Institutes of Biomedical Sciences, Fudan University, Shanghai, People's Republic of China
| | - Jia Fan
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China.,Institutes of Biomedical Sciences, Fudan University, Shanghai, People's Republic of China
| | - Ying-Hong Shi
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China
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Ye J, Xie X, Liu B, Zhang X, Wang W, Huang X, Lu M, Huang G. Imaging Features on Contrast-Enhanced Ultrasound and Clinical Characteristics of Hepatitis B Virus-Related Combined Hepatocellular-Cholangiocarcinoma: Comparison with Hepatitis B Virus-Related Hepatocellular Carcinoma. ULTRASOUND IN MEDICINE & BIOLOGY 2017; 43:2530-2536. [PMID: 28847498 DOI: 10.1016/j.ultrasmedbio.2017.07.016] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/28/2017] [Revised: 07/18/2017] [Accepted: 07/20/2017] [Indexed: 06/07/2023]
Abstract
The objective of this study was to compare the clinical characteristics and imaging features on contrast-enhanced ultrasound (CEUS) of hepatitis B virus (HBV)-related combined hepatocellular-cholangiocarcinoma (CHC) and hepatocellular carcinoma (HCC). Thirty-one pathologically proven CHCs were included and 31 HCCs were randomly selected as controls. Elevated carbohydrate antigen (CA) 19-9 alone and simultaneous elevation of α-fetoprotein and CA19-9 were more frequent in CHC than in HCC patients (p = 0.004 and 0.029, respectively). On CEUS, homogeneous, heterogeneous and peripheral irregular rim-like enhancement was illustrated in 8 (25.8%), 12 (38.7%) and 11 (35.5%) CHCs and in 6 (19.4%), 23 (74.1%) and 2 (6.5%) HCCs, respectively (p = 0.007). Multivariate logistic regression analysis revealed CA19-9 elevation (p = 0.011, odds ratio [OR] = 6.545) and peripheral irregular rim-like enhancement on CEUS (p = 0.017, OR = 7.718) were independent variables. A receiver operating characteristic curve was plotted and the area under the curve was 0.740. CHC should be watched for in HBV-infected patients with liver tumor manifesting peripheral irregular rim-like enhancement on CEUS, accompanied by CA19-9 elevation.
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Affiliation(s)
- Jieyi Ye
- Division of Interventional Ultrasound, Department of Medical Ultrasonics, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China; and Institute of Diagnostic and Interventional Ultrasound, Sun Yat-Sen University, Guangzhou, China
| | - Xiaoyan Xie
- Division of Interventional Ultrasound, Department of Medical Ultrasonics, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China; and Institute of Diagnostic and Interventional Ultrasound, Sun Yat-Sen University, Guangzhou, China
| | - Baoxian Liu
- Division of Interventional Ultrasound, Department of Medical Ultrasonics, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China; and Institute of Diagnostic and Interventional Ultrasound, Sun Yat-Sen University, Guangzhou, China
| | - Xiaoer Zhang
- Division of Interventional Ultrasound, Department of Medical Ultrasonics, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China; and Institute of Diagnostic and Interventional Ultrasound, Sun Yat-Sen University, Guangzhou, China
| | - Wei Wang
- Division of Interventional Ultrasound, Department of Medical Ultrasonics, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China; and Institute of Diagnostic and Interventional Ultrasound, Sun Yat-Sen University, Guangzhou, China
| | - Xiaowen Huang
- Division of Interventional Ultrasound, Department of Medical Ultrasonics, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China; and Institute of Diagnostic and Interventional Ultrasound, Sun Yat-Sen University, Guangzhou, China
| | - Mingde Lu
- Division of Interventional Ultrasound, Department of Medical Ultrasonics, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China; and Institute of Diagnostic and Interventional Ultrasound, Sun Yat-Sen University, Guangzhou, China
| | - Guangliang Huang
- Division of Interventional Ultrasound, Department of Medical Ultrasonics, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China; and Institute of Diagnostic and Interventional Ultrasound, Sun Yat-Sen University, Guangzhou, China.
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Gera S, Ettel M, Acosta-Gonzalez G, Xu R. Clinical features, histology, and histogenesis of combined hepatocellular-cholangiocarcinoma. World J Hepatol 2017; 9:300-309. [PMID: 28293379 PMCID: PMC5332419 DOI: 10.4254/wjh.v9.i6.300] [Citation(s) in RCA: 74] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2016] [Revised: 11/08/2016] [Accepted: 01/03/2017] [Indexed: 02/06/2023] Open
Abstract
Combined hepatocellular-cholangiocarcinoma (CHC) is a rare tumor with poor prognosis, with incidence ranging from 1.0%-4.7% of all primary hepatic tumors. This entity will be soon renamed as hepato-cholangiocarcinoma. The known risk factors for hepatocellular carcinoma (HCC) have been implicated for CHC including viral hepatitis and cirrhosis. It is difficult to diagnose this tumor pre-operatively. The predominant histologic component within the tumor largely determines the predominant radiographic features making it a difficult distinction. Heterogeneous and overlapping imaging features of HCC and cholangiocarcinoma should raise the suspicion for CHC and multiple core biopsies (from different areas of tumor) are recommended before administering treatment. Serum tumor markers CA19-9 and alpha-fetoprotein can aid in the diagnosis, but it remains a challenging diagnosis prior to resection. There is sufficient data to support bipotent hepatic progenitor cells as the cell of origin for CHC. The current World Health Organization classification categorizes two main types of CHC based on histo-morphological features: Classical type and CHC with stem cell features. Liver transplant is one of the available treatment modalities with other management options including transarterial chemoembolization, radiofrequency ablation, and percutaneous ethanol injection. We present a review paper on CHC highlighting the risk factors, origin, histological classification and therapeutic modalities.
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Mao Y, Xu S, Hu W, Huang J, Wang J, Zhang R, Li S. Imaging features predict prognosis of patients with combined hepatocellular-cholangiocarcinoma. Clin Radiol 2016; 72:129-135. [PMID: 27916195 DOI: 10.1016/j.crad.2016.11.003] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2016] [Revised: 10/31/2016] [Accepted: 11/02/2016] [Indexed: 12/30/2022]
Abstract
AIM To evaluate the prognostic value of imaging patterns in combined hepatocellular-cholangiocarcinoma. MATERIALS AND METHODS A total of 36 patients with histopathologically confirmed combined hepatocellular-cholangiocarcinoma were enrolled. Pretreatment imaging was conducted to evaluate the tumour enhancement patterns, based on which the disease was classified as two subtypes: radiographic hepatocellular carcinoma-dominant (n=26) and radiographic cholangiocarcinoma-dominant (n=10). Moreover, based on the proportion of components, all combined hepatocellular-cholangiocarcinoma cases were divided into histopathological hepatocellular carcinoma-dominant (n=26) or histopathological cholangiocarcinoma-dominant (n=10). The Kaplan-Meier method was used to compare patient outcome between the two subtypes of each classification. Univariate Cox regression analysis were employed to evaluate the prognostic relevance of the imaging and histopathological classification. RESULTS Consistency between histopathological and imaging classification was not high. Only 66.7% of patients had consistent classification. Moreover, the median overall survival of the radiographic cholangiocarcinoma-dominant and radiographic hepatocellular carcinoma-dominant population was 15.03 and 40.4 months, respectively (p=0.012); however, no significant difference was observed between histopathological type, with median overall survival being 32.07 and 40.4 months in the histopathological cholangiocarcinoma-dominant group and histopathological hepatocellular carcinoma-dominant group, respectively (p=0.784). CONCLUSION There was an association between imaging patterns and overall survival in combined hepatocellular-cholangiocarcinoma. Postoperative re-evaluation of imaging patterns could help to assess patient outcome.
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Affiliation(s)
- Y Mao
- State Key Laboratory of Oncology in Southern China, Guangzhou, 510060, China; Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, No. 651 Dongfeng Road East, 510060, Guangzhou, China
| | - S Xu
- Department of Ultrasound, The Third Affiliated Hospital of Sun Yat-Sen University, 600 Tianhe Road, Guangzhou, 510630, Guangdong Province, PR China
| | - W Hu
- State Key Laboratory of Oncology in Southern China, Guangzhou, 510060, China; Department of Pathology, Sun Yat-Sen University Cancer Center, No. 651 Dongfeng Road East, 510060, Guangzhou, China
| | - J Huang
- State Key Laboratory of Oncology in Southern China, Guangzhou, 510060, China; Department of Pathology, Sun Yat-Sen University Cancer Center, No. 651 Dongfeng Road East, 510060, Guangzhou, China
| | - J Wang
- State Key Laboratory of Oncology in Southern China, Guangzhou, 510060, China; Department of Ultrasound, Sun Yat-Sen University Cancer Center, No. 651 Dongfeng Road East, 510060, Guangzhou, China
| | - R Zhang
- State Key Laboratory of Oncology in Southern China, Guangzhou, 510060, China; Department of Radiology, Sun Yat-Sen University Cancer Center, No. 651 Dongfeng Road East, 510060, Guangzhou, China.
| | - S Li
- State Key Laboratory of Oncology in Southern China, Guangzhou, 510060, China; Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, No. 651 Dongfeng Road East, 510060, Guangzhou, China.
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Clinicopathological Features and Post-resection Prognosis of Double Primary Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma. World J Surg 2016; 41:825-834. [DOI: 10.1007/s00268-016-3787-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
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