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Shin H, Yu SJ. A concise review of updated global guidelines for the management of hepatocellular carcinoma: 2017-2024. JOURNAL OF LIVER CANCER 2025; 25:19-30. [PMID: 39925090 PMCID: PMC12010826 DOI: 10.17998/jlc.2025.02.03] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/25/2024] [Revised: 01/30/2025] [Accepted: 02/03/2025] [Indexed: 02/11/2025]
Abstract
Many guidelines for hepatocellular carcinoma (HCC) have been published and are regularly updated worldwide. HCC management involves a broad range of treatment options and requires multidisciplinary care, resulting in significant heterogeneity in management practices across international communities. To support standardized care for HCC, we systematically appraised 13 globally recognized guidelines and expert consensus statements, including five from Asia, four from Europe, and four from the United States. These guidelines share similarities but reveal notable discrepancies in surveillance strategies, treatment allocation, and other recommendations. Geographic differences in tumor biology (e.g., prevalence of viral hepatitis, alcohol-related liver disease, or metabolic dysfunction-associated steatotic liver disease) and disparities in available medical resources (e.g., organ availability, healthcare infrastructure, and treatment accessibility) complicate the creation of universally applicable guidelines. Previously, significant gaps existed between Asian and Western guidelines, particularly regarding treatment strategies. However, these differences have diminished over the years. Presently, variations are often more attributable to publication dates than to regional differences. Nonetheless, Asia-Pacific experts continue to diverge from the Barcelona Clinic Liver Cancer system, particularly with respect to surgical resection and locoregional therapies, which are viewed as overly conservative in Western guidelines. Advancements in systemic therapies have prompted ongoing updates to these guidelines. Given that each set of guidelines reflects distinct regional characteristics, strengths, and limitations, fostering collaboration and mutual complementarity is essential for addressing discrepancies and advancing global HCC care.
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Affiliation(s)
- Hyunjae Shin
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
- Liver Research Institute, Seoul National University, Seoul, Korea
| | - Su Jong Yu
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
- Liver Research Institute, Seoul National University, Seoul, Korea
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Yang SQ, Shi YS, Zou RQ, Dai YS, Liu F, Hu HJ, Li FY. Development and validation of an early recurrence predictive model for intrahepatic cholangiocarcinoma based on a systematic review and meta-analysis of 17 cohorts. Curr Probl Surg 2024; 61:101639. [PMID: 39647976 DOI: 10.1016/j.cpsurg.2024.101639] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2024] [Revised: 09/22/2024] [Accepted: 09/27/2024] [Indexed: 12/10/2024]
Affiliation(s)
- Si-Qi Yang
- Division of Biliary Tract Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Yu-Shan Shi
- Clinical Medical College, Ningxia Medical University, Ningxia Province, China
| | - Rui-Qi Zou
- Division of Biliary Tract Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Yu-Shi Dai
- Division of Biliary Tract Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Fei Liu
- Division of Biliary Tract Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Hai-Jie Hu
- Division of Biliary Tract Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
| | - Fu-Yu Li
- Division of Biliary Tract Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
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Zhou ZJ, Ye YH, Hu ZQ, Hou YR, Liu KX, Sun RQ, Wang PC, Luo CB, Li J, Zou JX, Zhou J, Fan J, Song CL, Zhou SL. Whole-exome sequencing reveals genomic landscape of intrahepatic cholangiocarcinoma and identifies SAV1 as a potential driver. Nat Commun 2024; 15:9960. [PMID: 39551842 PMCID: PMC11570600 DOI: 10.1038/s41467-024-54387-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Accepted: 11/07/2024] [Indexed: 11/19/2024] Open
Abstract
Intrahepatic cholangiocarcinoma (ICC) is the second most common primary hepatic malignancy after hepatocellular carcinoma, with poor prognosis and limited treatment options. The genomic features of ICC in Chinese patients remain largely unknown. In this study, we perform deep whole-exome sequencing of 204 Chinese primary ICCs and characterize genomic alterations and clonal evolution, and reveal their associations with patient outcomes. We identify six mutational signatures, including Signatures A and F, which are highly similar to previously described signatures linked to aristolochic acid and aflatoxin exposures, respectively. We also identify 13 significantly mutated genes in the ICC samples, including SAV1. We find that SAV1 was mutated in 2.9% (20/672) of 672 ICC samples. SAV1 mutation is associated with lower SAV1 protein levels, higher rates of tumor recurrence, and shorter overall patient survival. Biofunctional investigations reveal a tumor-suppressor role of SAV1: its inactivation suppresses Hippo signaling, leading to YAP activation, thereby promoting tumor growth and metastasis. Collectively, our results delineate the genomic landscape of Chinese ICCs and identify SAV1 as a potential driver of ICC.
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Affiliation(s)
- Zheng-Jun Zhou
- Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yu-Hang Ye
- Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Zhi-Qiang Hu
- Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yue-Ru Hou
- Institute of Cancer Stem Cell, Dalian Medical University, Dalian, Liaoning, China
| | - Kai-Xuan Liu
- Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Rong-Qi Sun
- Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Peng-Cheng Wang
- Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Chu-Bin Luo
- Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jia Li
- Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Ji-Xue Zou
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jian Zhou
- Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jia Fan
- Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Cheng-Li Song
- Institute of Cancer Stem Cell, Dalian Medical University, Dalian, Liaoning, China.
| | - Shao-Lai Zhou
- Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China.
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
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Qiu P, Feng Y, Zhao K, Shi Y, Li X, Deng Z, Wang J. Predictive models and treatment efficacy for liver cancer patients with bone metastases: A comprehensive analysis of prognostic factors and nomogram development. Heliyon 2024; 10:e38038. [PMID: 39386874 PMCID: PMC11462488 DOI: 10.1016/j.heliyon.2024.e38038] [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: 09/07/2023] [Revised: 09/16/2024] [Accepted: 09/16/2024] [Indexed: 10/12/2024] Open
Abstract
Background Bone metastasis considerably undermines the prognosis of advanced primary liver cancer patients. Though its impact is well-recognized, the clinical field still lacks robust predictive models that can accurately forecast patient outcomes and aid in treatment effectiveness evaluation. Addressing this gap is paramount for improving patient management and survival. Materials and methods We conducted an extensive analysis using data from the SEER database (2010-2020). COX regression analysis was applied to identify prognostic factors for primary liver cancer with bone metastasis (PLCBM). Nomograms were developed and validated to predict survival outcomes in PLCBM patients. Additionally, propensity score matching and Kaplan-Meier survival analyses lent additional insight by dissecting the survival advantage conferred by various treatment strategies. Results A total of 470 patients with PLCBM were included in our study. The median overall survival (OS) and cancer-specific survival (CSS) for these patients were both 5 months. We unveiled several independent prognosticators for OS and CSS, spanning demographic to therapeutic parameters like marital status, cancer grade, histological type, and treatments received. This discovery enabled the formulation of two novel nomograms-now verified to eclipse the predictive prowess of the traditional TNM staging system regarding discrimination and clinical utility. Additionally, propensity score matching analysis showed the effectiveness of surgeries, radiotherapy, and chemotherapy in improving OS and CSS outcomes for PLCBM patients. Conclusions Our investigation stands out by introducing pioneering nomograms for prognostic evaluation in PLCBM, a leap forward compared to existing tools. Far exceeding mere academic exercise, these nomograms hold immense clinical value, serving as a foundation for nuanced risk stratification systems and delivering dynamic, interactive guides, allowing healthcare professionals and patients to assess individual bone metastasis survival probabilities and personalize treatment selection.
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Affiliation(s)
- Peng Qiu
- Department of Biliary and Pancreatic Surgery, Cancer Research Center Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yunxiang Feng
- Department of Biliary and Pancreatic Surgery, Cancer Research Center Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Kai Zhao
- Department of Biliary and Pancreatic Surgery, Cancer Research Center Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yuanxin Shi
- Department of Biliary and Pancreatic Surgery, Cancer Research Center Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiangyu Li
- Department of Biliary and Pancreatic Surgery, Cancer Research Center Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zhengdong Deng
- Department of Pediatric Surgery, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jianming Wang
- Department of Biliary and Pancreatic Surgery, Cancer Research Center Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Affiliated Tianyou Hospital, Wuhan University of Science & Technology, Wuhan, China
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Kolck J, Hosse C, Beetz NL, Auer TA, Marth AA, Segger L, Krenzien F, Lurje G, Pelzer U, Geisel D, Schöning W, Fehrenbach U. Beyond body mass index: Body composition profiling for perioperative risk stratification in intrahepatic cholangiocarcinoma patients. Cancer Rep (Hoboken) 2024; 7:e2070. [PMID: 39324689 PMCID: PMC11425665 DOI: 10.1002/cnr2.2070] [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: 09/07/2023] [Revised: 02/25/2024] [Accepted: 03/30/2024] [Indexed: 09/27/2024] Open
Abstract
BACKGROUND AND AIMS Intrahepatic cholangiocarcinoma (iCC) is an aggressive tumor, usually detected at an advanced stage. Our aim was to investigate the potential of body composition analysis (BCA) derived from presurgical staging computed tomography (CT) in predicting perisurgical complications. METHODS In this retrospective cohort study, we enrolled 86 patients who underwent CT imaging prior to liver surgery. Cox and logistic regression were performed to assess risk factors for prolonged hospital and intensive care unit (ICU) stays, as well as the occurrence of various complications. BCA parameters served as covariates besides conventional risk factors. RESULTS Postoperative complications after resection of iCC significantly prolonged the overall length of hospitalization (p < .001). Presence of sarcopenia was associated with longer ICU stays. Complications were common, with 62.5% classified as Clavien-Dindo grade IIIa or lower and 37.5% as more severe. Subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were identified as risk factors for complications, including bile leakage (in 24 cases, p = .025), pleural effusions (in 26 cases, p = .025), and intra-abdominal abscess formation (in 24 cases, p = .043). SAT was associated with severe complications requiring interventional therapy, whereas VAT was correlated with abscess formation. Despite normal prevalence of obesity (22%), body mass index (BMI) did not have an impact on the development of perioperative complications. CONCLUSION BCA is a useful tool for preoperative risk stratification in patients with iCC and is superior to BMI assessment. Increased SAT and VAT were associated with the risk of perisurgical complications, prolonging hospitalization. Therefore, BCA derived from routine staging CT should be considered in the preoperative assessment of patients with iCC.
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Affiliation(s)
- Johannes Kolck
- Department of RadiologyCKV, Charité – Universitätsmedizin BerlinBerlinGermany
- Berlin Institute of Health at Charité – Universitätsmedizin BerlinBerlinGermany
| | - Clarissa Hosse
- Department of RadiologyCKV, Charité – Universitätsmedizin BerlinBerlinGermany
| | - Nick Lasse Beetz
- Department of RadiologyCKV, Charité – Universitätsmedizin BerlinBerlinGermany
- Berlin Institute of Health at Charité – Universitätsmedizin BerlinBerlinGermany
| | - Timo Alexander Auer
- Department of RadiologyCKV, Charité – Universitätsmedizin BerlinBerlinGermany
- Berlin Institute of Health at Charité – Universitätsmedizin BerlinBerlinGermany
| | | | - Laura Segger
- Department of RadiologyCKV, Charité – Universitätsmedizin BerlinBerlinGermany
| | - Felix Krenzien
- Berlin Institute of Health at Charité – Universitätsmedizin BerlinBerlinGermany
- Department of Surgery CCM/CVKCharité – Universitätsmedizin BerlinBerlinGermany
| | - Georg Lurje
- Department of Surgery CCM/CVKCharité – Universitätsmedizin BerlinBerlinGermany
| | - Uwe Pelzer
- Department of Hematology, Oncology and Cancer ImmunologyCharité – Universitätsmedizin BerlinBerlinGermany
| | - Dominik Geisel
- Department of RadiologyCKV, Charité – Universitätsmedizin BerlinBerlinGermany
| | - Wenzel Schöning
- Department of Surgery CCM/CVKCharité – Universitätsmedizin BerlinBerlinGermany
| | - Uli Fehrenbach
- Department of RadiologyCKV, Charité – Universitätsmedizin BerlinBerlinGermany
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Zhao C, Li X, Luo L, Chen C, He C. Modified staging system of positive lymph nodes based nomogram in intrahepatic cholangiocarcinoma. Cancer Cell Int 2023; 23:148. [PMID: 37516863 PMCID: PMC10386250 DOI: 10.1186/s12935-023-03005-6] [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: 02/02/2023] [Accepted: 07/26/2023] [Indexed: 07/31/2023] Open
Abstract
BACKGROUND Intrahepatic cholangiocarcinoma (iCCA) presents the similar trend and prevalence of lymph node metastasis to other biliary tract cancer. There is still a necessity and possibility for the current classification of lymph node in the 8th TNM of iCCA, which is the same as the criteria of hepatoma carcinoma (HCC), to further improve the prognostic capacity. We aim to explore the optimal positive lymph nodes cutoff value that could predict the survival outcomes of patients with iCCA and further establish a prognostic nomogram. METHOD Clinical characteristics were retrospectively collected in 292 patients with iCCA from Sun Yat-sen University Cancer Center (SYSUCC) for preliminary analysis. A retrospective analysis of 107 patients with iCCA in the First Hospital of Dalian Medical University (FHDMU) was performed for verification. R software was used to determine the optimal cutoff value of positive lymph nodes (PLN) and further establish the nomogram with the Cox regression model in the primary cohort. RESULTS In those patients who were graded into the N1 stage in 8th TNM staging system, the patients with PLN between 1 and 3 showed significantly better overall survival than those patients with more than 4 PLN (P < 0.0001). Moreover, there was a significant correlation between the new PLN classification and adverse clinical characteristic including Micro Invasion (P = 0.001), Lymph Vessel Invasion (P = 0.040), Satellite Sites (P < 0.001), and Tumor Size (P = 0.005). The PLN and ELN were both independent prognostic factors for survival outcomes in the multivariate analysis, and further showed large contribution to the nomogram. The nomogram achieved a satisfied C-index of 0.813 for overall survival (OS), 0.869 for progression-free survival (PFS) in the primary cohort, and 0.787 for OS, 0.762 for PFS in the validation cohort. CONCLUSION The modified classification of PLN in iCCA could accurately stratify the N1 stage patients in 8th TNM staging system into two groups with significantly different overall survival. The development of this nomogram can offer new evidence to precisely post-operative management of iCCA patients.
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Affiliation(s)
- Chongyu Zhao
- Department of Hepatobiliary Surgery, Xinqiao Hospital, Army Medical University, Chongqing, P. R. China
| | - Xiyuan Li
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P. R. China
- Department of Head and Neck Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P. R. China
| | - Li Luo
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P. R. China
| | - Cheng Chen
- Department of Cardiology, The First Affiliated Hospital of Dalian Medical University, Dalian, P. R. China
| | - Chaobin He
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P. R. China.
- Department of Pancreatobiliary Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P. R. China.
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Ni J, Huang M, Ji W, Wang L, Sun T. Recent advances in Surface-enhanced Raman Scattering for Liver Cancer Detection. CHINESE JOURNAL OF ANALYTICAL CHEMISTRY 2022. [DOI: 10.1016/j.cjac.2022.100180] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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Zhao C, He C, Lu J, Huang X, Chen C, Lin X. Progression Patterns and Post-Progression Survival in Recurred Intrahepatic Cholangiocarcinoma Patients: A Novel Prognostic Nomogram Based on Multicenter Cohorts. Front Oncol 2022; 12:832038. [PMID: 35463346 PMCID: PMC9033166 DOI: 10.3389/fonc.2022.832038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Accepted: 03/09/2022] [Indexed: 11/13/2022] Open
Abstract
BackgroundThe post-progression survival (PPS) of recurred intrahepatic cholangiocarcinoma (iCCA) patients relates to the characteristics of tumor progression. Moreover, the prediction model of PPS in those patients has not been well established. This study aimed at developing a novel nomogram for predicting PPS in recurred iCCA patients.MethodClinical characteristics were retrospectively collected in 396 patients diagnosed with iCCA from cohorts of Sun Yat-sen University Cancer Center (SYSUCC) and the First Hospital of Dalian Medical University (FHDMU). The PPS in patients with different progression patterns was investigated. The nomogram of PPS was established with the Cox regression model in the primary cohort. Then the nomogram was verified in the external validation cohort.ResultsLiver progression was the commonest pattern (42.08%) in recurred iCCA patients, while patients with local LN progression had significantly better PPS than those with other patterns. The independent prognostic factors comprised elevated CEA levels, tumor differentiation, N stage 8th, adjuvant therapy, Local LN metastasis, Liver Metastasis only, and Multiple Metastasis. The nomogram constructed on these factors achieved satisfied C-indexes of 0.794 (95% CI 0.769–0.828) and 0.827 (0.779–0.876) for the training and validation cohorts, respectively. These values were significantly higher than those of the 8th TNM stage system (all p < 0.001). The recurred iCCA patients could be precisely classified into high- and low-risk groups according to the cutoff point of this nomogram (p < 0.01).ConclusionThe investigation of progression patterns and the development of this nomogram can offer new evidence to precisely postoperative and post-progression management of iCCA patients.
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Affiliation(s)
- Chongyu Zhao
- Department of Pancreatobiliary Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Chaobin He
- Department of Pancreatobiliary Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
- *Correspondence: Xiaojun Lin, ; Chaobin He,
| | - Jiawei Lu
- Department of Oncology, The Second Hospital of Dalian Medical University, Dalian, China
| | - Xin Huang
- Department of Pancreatobiliary Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Cheng Chen
- Department of Cardiology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Xiaojun Lin
- Department of Pancreatobiliary Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
- *Correspondence: Xiaojun Lin, ; Chaobin He,
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Zhang X, Zhou Y, Wu Z, Peng W, Li C, Yan L, Yang J, Wen T. Double-Negative α-Fetoprotein and Carbohydrate Antigen 19-9 Predict a Good Prognosis in Intrahepatic Cholangiocarcinoma: A Propensity Score Matching Analysis. Clin Transl Gastroenterol 2021; 12:e00425. [PMID: 34751187 PMCID: PMC8580197 DOI: 10.14309/ctg.0000000000000425] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Accepted: 09/23/2021] [Indexed: 02/05/2023] Open
Abstract
INTRODUCTION Carbohydrate antigen 19-9 (CA19-9) and α-fetoprotein (AFP) are routinely tested in patients with liver malignancies before surgery. However, few reports have explored the relevance of the expression pattern of these 2 tumor markers regarding the prognosis of intrahepatic cholangiocarcinoma (ICC). We herein combined these 2 tumor markers to investigate the influence on ICC malignancy and patient prognosis. METHODS From March 2009 to December 2019, 519 consecutive patients with newly diagnosed ICC who underwent R0 resection were enrolled and followed. The relationships between clinicopathological parameters and these 2 tumor markers were analyzed. Propensity score matching was used to eliminate the baseline differences. RESULTS A lower proportion of patients with double-negative AFP and CA19-9 had advanced tumor-node-metastasis stage, larger tumor diameter, multiple tumors, lymph node metastasis, microvascular invasion, and perineural invasion. With propensity score matching, patients were divided into double-negative and non-double-negative groups, with 128 patients in each group, and the 5-year recurrence-free survival and overall survival rates were 33.8 vs 15.2 (P < 0.001) and 45.3 vs 19.0, respectively (P < 0.001). In the multivariate Cox analyses, double negativity for the 2 tumor markers was an independent factor for recurrence-free survival (hazard ratios, 0.578; 95% CI, 0.442-0.755, P < 0.001) and overall survival (hazard ratios, 0.567; 95% CI, 0.434-0.741, P < 0.001). DISCUSSION Double negativity for CA19-9 and AFP indicated less invasive tumor characteristics in patients with ICC. Patients with double-negative tumor markers achieved better outcomes than those with non-double-negative markers, which is meaningful for prognostic counseling and therapeutic triage.
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Affiliation(s)
- Xiaoyun Zhang
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
- Laboratory of Liver Transplantation, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu Sichuan Province, China
- Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, China.
| | - Yongjie Zhou
- Laboratory of Liver Transplantation, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu Sichuan Province, China
- Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, China.
| | - Zhenru Wu
- Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, China.
| | - Wei Peng
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
- Laboratory of Liver Transplantation, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu Sichuan Province, China
| | - Chuan Li
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
- Laboratory of Liver Transplantation, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu Sichuan Province, China
| | - Lvnan Yan
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
- Laboratory of Liver Transplantation, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu Sichuan Province, China
| | - Jiayin Yang
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
- Laboratory of Liver Transplantation, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu Sichuan Province, China
| | - Tianfu Wen
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
- Laboratory of Liver Transplantation, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu Sichuan Province, China
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Hao X, Liu B, Hu X, Wei J, Han Y, Liu X, Chen Z, Li J, Bai J, Chen Y, Wang J, Niu M, Tian J. A Radiomics-based Approach for Predicting Early Recurrence in Intrahepatic Cholangiocarcinoma after Surgical Resection: A Multicenter Study. ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY. IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY. ANNUAL INTERNATIONAL CONFERENCE 2021; 2021:3659-3662. [PMID: 34892030 DOI: 10.1109/embc46164.2021.9630029] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
This work aimed to develop a noninvasive and reliable computed tomography (CT)-based imaging biomarker to predict early recurrence (ER) of intrahepatic cholangiocarcinoma (ICC) via radiomics analysis. In this retrospective study, a total of 177 ICC patients were enrolled from three independent hospitals. Radiomic features were extracted on CT images, then 11 feature selection algorithms and 4 classifiers were to conduct a multi-strategy radiomics modeling. Six established radiomics models were selected as stable ones by robustness-based rule. Among those models, Max-Relevance Min-Redundancy (MRMR) combined with Gradient Boosting Machine (GBM) yielded the highest areas under the receiver operating characteristics curve (AUCs) of 0.802 (95% confidence interval [CI]: 0.727-0.876) and 0.781 (95% CI: 0.655-0.907) in the training and test cohorts, respectively. To evaluate the generalization of the developed radiomics model, stratification analysis was performed regarding different centers. The MRMR-GBM-based model manifested good generalization with comparable AUCs in each hospital (p > 0.05 for paired comparison). Thus, the MRMR-GBM-based model could offer a potential imaging biomarker to assist the prediction of ER in ICC in a noninvasive manner.Clinical Relevance-The proposed radiomics model achieved satisfactory accuracy and good generalization ability in predicting ER in ICC, which might assist personalized surveillance and clinical treatment strategy making.
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Luo D, Zhao D, Zhang M, Hu C, Li H, Zhang S, Chen X, Huttad L, Li B, Jin C, Lin C, Han B. Alternative Splicing-Based Differences Between Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma: Genes, Immune Microenvironment, and Survival Prognosis. Front Oncol 2021; 11:731993. [PMID: 34760694 PMCID: PMC8574058 DOI: 10.3389/fonc.2021.731993] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Accepted: 09/29/2021] [Indexed: 12/17/2022] Open
Abstract
Alternative splicing (AS) event is a novel biomarker of tumor tumorigenesis and progression. However, the comprehensive analysis of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) is lacking. Differentially expressed analysis was used to identify the differentially expressed alternative splicing (DEAS) events between HCC or ICC tissues and their normal tissues. The correlation between DEAS events and functional analyses or immune features was evaluated. The cluster analysis based on DEAS can accurately reflect the differences in the immune microenvironment between HCC and ICC. Forty-five immune checkpoints and 23 immune features were considered statistically significant in HCC, while only seven immune checkpoints and one immune feature in ICC. Then, the prognostic value of DEAS events was studied, and two transcripts with different basic cell functions (proliferation, cell cycle, invasion, and migration) were produced by ADHFE1 through alternative splicing. Moreover, four nomograms were established in conjunction with relevant clinicopathological factors. Finally, we found two most significant splicing factors and further showed their protein crystal structure. The joint analysis of the AS events in HCC and ICC revealed novel insights into immune features and clinical prognosis, which might provide positive implications in HCC and ICC treatment.
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Affiliation(s)
- Dingan Luo
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Deze Zhao
- Department of Thoracic Surgery, Xiangya Hospital, Central South University, Changsha, China
| | - Mao Zhang
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Chuan Hu
- Medical College, Qingdao University, Qingdao, China
| | - Haoran Li
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Shun Zhang
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Xiaowu Chen
- Asian Liver Center, Department of Surgery, Medical School of Stanford University, Stanford, CA, United States
| | - Lakshmi Huttad
- Asian Liver Center, Department of Surgery, Medical School of Stanford University, Stanford, CA, United States
| | - Bailiang Li
- Department of Radiation Oncology, Medical School of Stanford University, Stanford, CA, United States
| | - Cheng Jin
- Department of Radiation Oncology, Medical School of Stanford University, Stanford, CA, United States
| | - Changwei Lin
- Department of Gastrointestinal Surgery, The Third Xiangya Hospital of Central South University, Changsha, China
| | - Bing Han
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
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12
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Zhang Y, Yu S, Zhu X, Ning X, Liu W, Wang C, Liu X, Zhao D, Zheng Y, Bao J. Explainable liver tumor delineation in surgical specimens using hyperspectral imaging and deep learning. BIOMEDICAL OPTICS EXPRESS 2021; 12:4510-4529. [PMID: 34457429 PMCID: PMC8367264 DOI: 10.1364/boe.432654] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Revised: 06/17/2021] [Accepted: 06/18/2021] [Indexed: 05/08/2023]
Abstract
Surgical removal is the primary treatment for liver cancer, but frequent recurrence caused by residual malignant tissue remains an important challenge, as recurrence leads to high mortality. It is unreliable to distinguish tumors from normal tissues merely under visual inspection. Hyperspectral imaging (HSI) has been proved to be a promising technology for intra-operative use by capturing the spatial and spectral information of tissue in a fast, non-contact and label-free manner. In this work, we investigated the feasibility of HSI for liver tumor delineation on surgical specimens using a multi-task U-Net framework. Measurements are performed on 19 patients and a dataset of 36 specimens was collected with corresponding pathological results serving as the ground truth. The developed framework can achieve an overall sensitivity of 94.48% and a specificity of 87.22%, outperforming the baseline SVM method by a large margin. In particular, we propose to add explanations on the well-trained model from the spatial and spectral dimensions to show the contribution of pixels and spectral channels explicitly. On that basis, a novel saliency-weighted channel selection method is further proposed to select a small subset of 5 spectral channels which provide essentially as much information as using all 224 channels. According to the dominant channels, the absorption difference of hemoglobin and bile content in the normal and malignant tissues seems to be promising markers that could be further exploited.
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Affiliation(s)
- Yating Zhang
- Department of Electronic Engineering, Tsinghua University, Beijing 100084, China
| | - Si Yu
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China
| | - Xueyu Zhu
- Department of Mathematics, University of Iowa, Iowa City, IA 52242, USA
| | - Xuefei Ning
- Department of Electronic Engineering, Tsinghua University, Beijing 100084, China
| | - Wei Liu
- Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China
| | - Chuting Wang
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China
| | - Xiaohu Liu
- Department of Electronic Engineering, Tsinghua University, Beijing 100084, China
- Currently with the School of Biomedical Engineering, School of Ophthalmology & Optometry, Wenzhou Medical University. Xueyuan Road 270, Wenzhou 325027, China
| | - Ding Zhao
- Department of Electronic Engineering, Tsinghua University, Beijing 100084, China
| | - Yongchang Zheng
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China
| | - Jie Bao
- Department of Electronic Engineering, Tsinghua University, Beijing 100084, China
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13
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Xu L, Wan Y, Luo C, Yang J, Yang P, Chen F, Wang J, Niu T. Integrating intratumoral and peritumoral features to predict tumor recurrence in intrahepatic cholangiocarcinoma. Phys Med Biol 2021; 66. [PMID: 34096890 DOI: 10.1088/1361-6560/ac01f3] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2020] [Accepted: 05/17/2021] [Indexed: 11/11/2022]
Abstract
Previous studies have suggested that the intratumoral texture features may reflect the tumor recurrence risk in intrahepatic cholangiocarcinoma (ICC). The peritumoral features may be associated with the distribution of microsatellites. Therefore, integrating the imaging features based on intratumoral and peritumoral areas may provide more accurate predictions in tumor recurrence (both early and late recurrences) than the predictions conducted based on the intratumoral area only. This retrospective study included 209 ICC patients. We divided the patient population into two sub-groups according to the order of diagnosis time: a training cohort (159 patients) and an independent validation cohort (50 patients). The MR imaging features were quantified based on the intratumoral and peritumoral (3 and 5 mm) areas. The radiomics signatures, clinical factor-based models and combined radiomics-clinical models were developed to predict the tumor recurrence. The prediction performance was measured based on the validation cohort using the area under receiver operating characteristic curve (AUC) index. For the prediction of early recurrence, the combined radiomics-clinical model of intratumoral area with 5 mm peritumoral area showed the highest performance (0.852(95% confidence interval (CI), 0.724-0.937)). The AUC for the clinical factor-based model was 0.805(95%CI, 0.668-0.903). For the prediction of late recurrence, the radiomics signature of intratumoral area with 5 mm peritumoral area had the optimal performance with an AUC of 0.735(95%CI, 0.591-0.850). The clinical factor-based showed inferior performance (0.598(95%CI, 0.450-0.735)). For both early and late recurrences prediction, the optimal models were all constructed using imaging features extracted based on intratumoral and peritumoral areas together. These suggested the importance of involving the intratumoral and peritumoral areas in the radiomics studies.
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Affiliation(s)
- Lei Xu
- Institute of Biomedical Engineering, Shenzhen Bay Laboratory, Shenzhen, People's Republic of China.,Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Institute of Translational Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China
| | - Yidong Wan
- Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Institute of Translational Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China
| | - Chen Luo
- Institute of Biomedical Engineering, Shenzhen Bay Laboratory, Shenzhen, People's Republic of China
| | - Jing Yang
- Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Institute of Translational Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China
| | - Pengfei Yang
- College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China
| | - Feng Chen
- Department of Radiology, the First Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China
| | - Jing Wang
- Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Institute of Translational Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China
| | - Tianye Niu
- Nuclear & Radiological Engineering and Medical Physics Programs, Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, Georgia, United States of America
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14
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Kim KM, Na JE, Shim SG, Sinn DH. Comparison of ICC patients with hepatitis B infection to those with no major risk factors for HCC. HPB (Oxford) 2021; 23:945-953. [PMID: 33132045 DOI: 10.1016/j.hpb.2020.10.011] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2020] [Revised: 09/10/2020] [Accepted: 10/14/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND There has been renewed interest in HBV-associated ICC, because it could share a common carcinogenesis disease process with HCC. We investigated whether there is a difference in clinical outcome between ICC patients with HBV infection and those without any major risk factors for HCC. METHODS A total of 253 curatively resected, surgically diagnosed ICC patients were analyzed and divided into two groups according to the presence or absence of major risk factors for HCC: an HBV group (n = 45) and a non-HCC-risk (NHR) group (n = 208). RESULTS Lymph node metastasis was more frequently observed in the NHR group (HBV vs. NHR: 8.89% vs. 24.52%, P = 0.027). Patients in the HBV group demonstrated more favorable survival than those in the NHR group. However, this difference was not statistically significant (5-year survival rate, 54.7% vs. 42.3%, P = 0.128). Cumulative recurrence rate in the HBV group was 62.2%, which was not significantly different from 63.0% in the NHR group (P = 1.000). CONCLUSION This study found that while ICC patients with HBV infection showed some favorable tumor characteristics, patients' stage-specific survival and recurrence rates were not significantly different compared to those without any major risk factors for HCC.
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Affiliation(s)
- Kwang Min Kim
- Department of Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, South Korea
| | - Ji Eun Na
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Sang Goon Shim
- Department of Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, South Korea
| | - Dong Hyun Sinn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
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15
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Chang KP, Lin SH, Chu YW. Artificial intelligence in gastrointestinal radiology: A review with special focus on recent development of magnetic resonance and computed tomography. Artif Intell Gastroenterol 2021; 2:27-41. [DOI: 10.35712/aig.v2.i2.27] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 03/21/2021] [Accepted: 04/20/2021] [Indexed: 02/06/2023] Open
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16
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Zhou Z, Wang P, Sun R, Li J, Hu Z, Xin H, Luo C, Zhou J, Fan J, Zhou S. Tumor-associated neutrophils and macrophages interaction contributes to intrahepatic cholangiocarcinoma progression by activating STAT3. J Immunother Cancer 2021; 9:e001946. [PMID: 33692217 PMCID: PMC7949476 DOI: 10.1136/jitc-2020-001946] [Citation(s) in RCA: 64] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/10/2021] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Tumor-associated neutrophils (TANs) and macrophages (TAMs) can each influence cancer growth and metastasis, but their combined effects in intrahepatic cholangiocarcinoma (ICC) remain unclear. METHODS We explored the distributions of TANs and TAMs in patient-derived ICC samples by multiplex immunofluorescent staining and tested their separate and combined effects on ICC in vitro and in vivo. We then investigated the mechanistic basis of the effects using PCR array, western blot analysis and ELISA experiments. Finally, we validated our results in a tissue microarray composed of primary tumor tissues from 359 patients with ICC. RESULTS The spatial distributions of TANs and TAMs were correlated with each other in patient-derived ICC samples. Interaction between TANs and TAMs enhanced the proliferation and invasion abilities of ICC cells in vitro and tumor progression in a mouse xenograft model of ICC. TANs and TAMs produced higher levels of oncostatin M and interleukin-11, respectively, in co-culture than in monoculture. Both of those cytokines activated STAT3 signaling in ICC cells. Knockdown of STAT3 abolished the protumor effect of TANs and TAMs on ICC. In tumor samples from patients with ICC, increased TAN and TAM levels were correlated with elevated p-STAT3 expression. All three of those factors were independent predictors of patient outcomes. CONCLUSIONS TANs and TAMs interact to promote ICC progression by activating STAT3.
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Affiliation(s)
- Zhengjun Zhou
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, China
| | - Pengcheng Wang
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, China
| | - Rongqi Sun
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, China
| | - Jia Li
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, China
| | - Zhiqiang Hu
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, China
| | - Haoyang Xin
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, China
| | - Chubin Luo
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, China
| | - Jian Zhou
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, China
| | - Jia Fan
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, China
| | - Shaolai Zhou
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, China
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17
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Sapisochin G, Ivanics T, Subramanian V, Doyle M, Heimbach JK, Hong JC. Multidisciplinary treatment for hilar and intrahepatic cholangiocarcinoma: A review of the general principles. Int J Surg 2020; 82S:77-81. [PMID: 32380231 DOI: 10.1016/j.ijsu.2020.04.067] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Revised: 04/25/2020] [Accepted: 04/28/2020] [Indexed: 02/07/2023]
Abstract
Cholangiocarcinoma (CCA) is a rare but devastating malignancy that presents late, and associated with a high mortality if untreated. CCA is locally aggressive and located in close proximity to vital structures i.e. the portal vein and hepatic artery. A complete extirpation of the tumor including microscopically detectable disease R0 resection offers the best possibility of long-term survival in patients with CCA. As such, the surgical approach to achieve a R0 resection is dictated by the location of the tumor and the presence of underlying liver disease. The present article focuses on the general principles of the multidisciplinary treatment of hilar and intrahepatic CCA.
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Affiliation(s)
- Gonzalo Sapisochin
- Multi-Organ Transplant and HPB Surgical Oncology, Division of General Surgery, University Health Network, Department of Surgery, University of Toronto, Canada
| | - Tommy Ivanics
- Multi-Organ Transplant and HPB Surgical Oncology, Division of General Surgery, University Health Network, Department of Surgery, University of Toronto, Canada
| | - Vijay Subramanian
- Transplant, Hepatobiliary and Pancreatic Surgery, Tampa General Hospital, Tampa, FL, USA
| | - Majella Doyle
- Division of Transplant and Hepatobiliary and Pancreatic Surgery, Department of Surgery, Washington University in St. Louis, St. Louis, MO, USA
| | - Julie K Heimbach
- Division of Transplant Surgery, Department of Surgery, Mayo Clinic, Rochester, MN, USA
| | - Johnny C Hong
- Division of Transplant Surgery, Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA.
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18
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Wang L, Lin ZG, Ke Q, Lou JY, Zheng SG, Bi XY, Wang JM, Guo W, Li FY, Wang J, Zheng YM, Li JD, Cheng S, Zhou WP, Zeng YY. Adjuvant transarterial chemoembolization following radical resection for intrahepatic cholangiocarcinoma: A multi-center retrospective study. J Cancer 2020; 11:4115-4122. [PMID: 32368294 PMCID: PMC7196258 DOI: 10.7150/jca.40358] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2019] [Accepted: 03/27/2020] [Indexed: 02/05/2023] Open
Abstract
Background and Aims: The prognosis of intrahepatic cholangiocarcinoma (ICC) after radical resection is far from satisfactory, but the effect of postoperative transarterial chemoembolization (p-TACE) remains controversial. This multi-center retrospective study was to evaluate the clinical value of p-TACE and identify the selected patients who would benefit from p-TACE. Methods: Data of ICC patients who underwent radical resection with/without p-TACE therapy was obtained from 12 hepatobiliary centers in China between Jan 2014 and Jan 2017. Overall survival (OS) was set as the primary endpoint, which was analyzed by the Kaplan-Meier method before and after propensity score matching (PSM). Subgroup analysis was conducted based on the established staging system and survival risk stratification. Results: A total of 335 patients were enrolled in this study, including 39 patients in the p-TACE group and 296 patients in the non-TACE group. Median OS in the p-TACE group was longer than that in the non-TACE group (63.0 months vs. 18.0 months, P=0.041), which was confirmed after 1:1 PSM (P=0.009). According to the 8th TNM staging system, patients with stage II and stage III stage would be benefited from p-TACE (P=0.021). Subgroup analysis stratified by risk factors showed that p-TACE could only benefit patients with risk factors <2 (P=0.027). Conclusion: Patients with ICC should be recommended to receive p-TACE following radical resection, especially for those with stage II, stage III or risk factors <2. However, the conclusion deserved further validation.
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Affiliation(s)
- Lei Wang
- Department of Radiation Oncology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou China, 350025
| | - Zi-Guo Lin
- Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou China, 350025
| | - Qiao Ke
- Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou China, 350025
| | - Jian-Ying Lou
- Department of hepatobiliary surgery, the Second Hospital affiliated to Zhejiang University, Hangzhou, China, 310009
| | - Shu-Guo Zheng
- Department of hepatobiliary surgery, the Southwest Hospital affiliated to the Army Medical University, Chongqing, China, 400038
| | - Xin-Yu Bi
- Department of Hepatobiliary Surgery, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China, 100021
| | - Jian-Ming Wang
- Department of hepatobiliary surgery, Tongji Hospital affiliated to affiliated to Tongji Medical College, Huazhong University of Science &Technology, Wuhan, Hubei, China, 430030
| | - Wei Guo
- Department of Hepatobiliary Surgery, Beijing Friendship Hospital affiliated to Capital Medical University, Beijing, China, 100053
| | - Fu-Yu Li
- Department of Hepatobiliary Surgery, the West China Hospital of Sichuan University, Chengdu, China, 610041
| | - Jian Wang
- Department of hepatobiliary surgery, Renji Hospital affiliated to Shanghai Jiaotong University, Shanghai, China, 200127
| | - Ya-Min Zheng
- Department of Hepatobiliary Surgery, Xuanwu Hospital affiliated to Capital Medical University, Beijing, China, 100050
| | - Jing-Dong Li
- Department of Hepatobiliary Surgery, the affiliated Hospital of Chuanbei Medical University, Nanchong, China, 637000
| | - Shi Cheng
- Department of Hepatobiliary Surgery, Tiantan Hospital affiliated to Capital Medical University, Beijing, China, 100050
| | - Wei-Ping Zhou
- Department of Hepatobiliary Surgery Ⅲ, Eastern Hepatobiliary Surgery Hospital, Secondary Military Medical University, Shanghai China, 200438
| | - Yong-Yi Zeng
- Department of Radiation Oncology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou China, 350025
- Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou China, 350025
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19
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Yang H, Wang J, Li Z, Yang Y, Yang L, Zhang Y, Shi Y, Cao Y, Zhou J, Wang Z, Chen Q. Risk Factors and Outcomes of Early Relapse After Curative Resection of Intrahepatic Cholangiocarcinoma. Front Oncol 2019; 9:854. [PMID: 31555597 PMCID: PMC6737003 DOI: 10.3389/fonc.2019.00854] [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: 07/14/2019] [Accepted: 08/19/2019] [Indexed: 12/24/2022] Open
Abstract
Early relapse after hepatectomy for intrahepatic cholangiocarcinoma (ICC) has a tremendous influence on the long-term survival outcomes of ICC patients. The purpose of our study was to investigate risk factors for early tumor relapse and confirm whether early relapse was correlated with ICC patients' long-term survival outcomes. Three hundred and twenty-two consecutive ICC patients undergoing partial hepatectomy at Liver Surgery Department of Zhongshan Hospital (Fudan University, Shanghai, China) between January 2005 and December 2011 were included in this retrospectively study. The definition of early relapse had been described as tumor relapse within 24 months after hepatectomy in ICC patients. We identified a total of 168 ICC patients with early relapse and 23 ICC patients with late relapse after hepatectomy. From the time of relapse, the long-term survival outcomes were worse among patients who had early vs. late relapse (median OS 16.5 vs. 44.7 months, respectively; P < 0.0001). The overall survival of the early relapse group was lower than that of the late relapse group (P < 0.0001). Multivariate Cox regression analysis indicated that multiple tumors (hazard ratio [HR], 1.951; 95% CI, 1.382-2.755; P < 0.001), lymphonodus metastasis (HR, 1.517; 95% CI, 1.061-2.168; P = 0.022), and higher serum CA19-9 levels (HR, 1.495; 95% CI, 1.095-2.039; P = 0.011) were independent risk factors of early relapse. Moreover, multiple tumors (HR, 1.641; 95% CI, 1.120-2.406; P = 0.011), lymphonodus metastasis (HR, 2.008; 95% CI, 1.367-2.949; P < 0.001), elevated NLR (HR, 1.921; 95% CI, 1.331-2.774; P < 0.001) and higher serum CA19-9 levels (HR, 1.990; 95% CI, 1.409-2.812; P < 0.001) were independent predictors of overall survival for ICC patients with early relapse. Collectively, our findings demonstrated that multiple tumors, lymphonodus metastasis, and higher serum CA19-9 levels were associated with the increased risks of early relapse and worse prognoses of ICC after curative-intent resection.
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Affiliation(s)
- Hua Yang
- Department of General Surgery, Shanghai Public Health Clinical Center, Zhongshan Hospital (South), Fudan University, Shanghai, China
| | - Jie Wang
- ENT Institute and Otorhinolaryngology Department, Eye & ENT Hospital, Fudan University, Shanghai, China
| | - Zehuan Li
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yi Yang
- Key Laboratory of Carcinogenesis and Cancer Invasion, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Ministry of Education, Shanghai, China
| | - Liuxiao Yang
- Key Laboratory of Carcinogenesis and Cancer Invasion, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Ministry of Education, Shanghai, China
| | - Yong Zhang
- Department of General Surgery, Shanghai Public Health Clinical Center, Zhongshan Hospital (South), Fudan University, Shanghai, China
| | - Yinghong Shi
- Key Laboratory of Carcinogenesis and Cancer Invasion, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Ministry of Education, Shanghai, China
| | - Ya Cao
- Key Laboratory of Carcinogenesis and Cancer Invasion, Cancer Research Institute, Central South University, Ministry of Education, Changsha, China
| | - Jian Zhou
- Key Laboratory of Carcinogenesis and Cancer Invasion, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Ministry of Education, Shanghai, China.,Institute of Biomedical Sciences, Fudan University, Shanghai, China.,State key Laboratory of Genetic Engineering, Fudan University, Shanghai, China
| | - Zheng Wang
- Key Laboratory of Carcinogenesis and Cancer Invasion, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Ministry of Education, Shanghai, China
| | - Qing Chen
- Department of General Surgery, Shanghai Public Health Clinical Center, Zhongshan Hospital (South), Fudan University, Shanghai, China
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20
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Gong ZJ, Cheng JW, Gao PT, Huang A, Sun YF, Zhou KQ, Hu B, Qiu SJ, Zhou J, Fan J, Yang XR. Clinical Characteristics and Prognostic Factors of Patients with Intrahepatic Cholangiocarcinoma with Fever: A Propensity Score Matching Analysis. Oncologist 2019; 24:997-1007. [PMID: 30910867 PMCID: PMC6656462 DOI: 10.1634/theoncologist.2018-0268] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2018] [Accepted: 02/04/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Patients with intrahepatic cholangiocarcinoma (ICC) rarely present fever as the initial symptom. We aimed to identify clinical characteristics and prognostic factors for these feverish patients. SUBJECTS, MATERIALS, AND METHODS This study retrospectively reviewed 31 patients with ICC with fever (≥38.0°C) treated at our hospital between January 2002 and December 2014. A propensity score was used to match patients with and without fever at a ratio of 1:2. RESULTS Patients with ICC with fever had higher serum γ-glutamyl transferase and carcinoembryonic antigen levels, larger tumors, poorer tumor differentiation, and worse prognosis (all p < .05) than those without fever. This was supported by propensity score matching (PSM) analysis. Univariate and multivariate analyses indicated that microvascular invasion, hilar lymph node metastasis, and temperature ≥ 38.6°C were related to prognosis. Patients with ICC with fever had higher levels of leucocytes, neutrophils, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) in peripheral blood before and after PSM analysis. Body temperature positively correlated with leucocytes (r = 0.599, p < .001), neutrophils (r = 0.644, p < .001), NLR (r = 0.681, p < .001), and PLR (r = 0.457, p = .010). CONCLUSION Patients with ICC with fever ≥38.0°C and ≥38.6°C had poor and extremely poor prognosis, respectively. Radical surgical treatment may improve the prognosis of patients with ICC with fever <38.6°C. However, systemic therapy (e.g., anti-inflammatory and immune therapy) may be preferable to surgery for these patients with fever ≥38.6°C. IMPLICATIONS FOR PRACTICE Patients with intrahepatic cholangiocarcinoma (ICC) with fever (≥38.0°C) as the initial symptom are extremely rare. Because their symptoms are similar to those of liver abscess, diagnosis is challenging, and most of these patients are already at an advanced stage at the time of diagnosis. Patients with ICC with fever had different clinical characteristics and worse prognosis than those without fever. The prognosis of those with temperature <38.6°C would be improved by timely surgical intervention. Those with fever ≥38.6°C had an extremely dismal outcome, although they all received radical surgical treatment. New therapeutic strategies are needed to improve survival for patients with ICC with temperature ≥38.6°C.
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Affiliation(s)
- Zi-Jun Gong
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, People's Republic of China
- Department of General Surgery, Zhongshan Hospital, Biliary Tract Diseases Institute, Fudan University, Shanghai, People's Republic of China
| | - Jian-Wen Cheng
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, People's Republic of China
| | - Pin-Ting Gao
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, People's Republic of China
| | - Ao Huang
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, People's Republic of China
| | - Yun-Fan Sun
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, People's Republic of China
| | - Kai-Qian Zhou
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, People's Republic of China
| | - Bo Hu
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, People's Republic of China
| | - Shuang-Jian Qiu
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, People's Republic of China
| | - Jian Zhou
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, People's Republic of China
- Institutes of Biomedical Sciences, Fudan University, Shanghai, People's Republic of China
| | - Jia Fan
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, People's Republic of China
- Institutes of Biomedical Sciences, Fudan University, Shanghai, People's Republic of China
| | - Xin-Rong Yang
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, People's Republic of China
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Min JH, Kim YK, Choi SY, Kang TW, Lee SJ, Kim JM, Ahn S, Cho H. Intrahepatic Mass-forming Cholangiocarcinoma: Arterial Enhancement Patterns at MRI and Prognosis. Radiology 2019; 290:691-699. [DOI: 10.1148/radiol.2018181485] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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22
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Zhang XF, Chakedis J, Bagante F, Beal EW, Lv Y, Weiss M, Popescu I, Marques HP, Aldrighetti L, Maithel SK, Pulitano C, Bauer TW, Shen F, Poultsides GA, Soubrane O, Martel G, Groot Koerkamp B, Guglielmi A, Itaru E, Pawlik TM. Implications of Intrahepatic Cholangiocarcinoma Etiology on Recurrence and Prognosis after Curative-Intent Resection: a Multi-Institutional Study. World J Surg 2018; 42:849-857. [PMID: 28879598 DOI: 10.1007/s00268-017-4199-9] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND We sought to investigate the prognosis of patients following curative-intent surgery for intrahepatic cholangiocarcinoma (ICC) stratified by hepatitis B (HBV-ICC), hepatolithiasis (Stone-ICC), and no identifiable cause (conventional ICC) etiologic subtype. METHODS 986 patients with HBV-ICC (n = 201), stone-ICC (n = 103), and conventional ICC (n = 682) who underwent curative-intent resection were identified from a multi-institutional database. Propensity score matching (PSM) was used to mitigate residual bias. RESULTS HBV-ICC patients more often had cirrhosis, earlier stage tumors, a mass-forming lesion, well-to-moderate tumor differentiation, and an R0 resection versus stone-ICC or conventional ICC patients. Five-year recurrence-free survival among HBV-ICC and conventional ICC patients was 23.9 and 17.8%, respectively, versus a recurrence-free of only 8.3% among patients with stone-ICC. Similarly, 5-year overall survival among patients with stone-ICC was only 18.3% compared with 48.9 and 38.0% for patients with HBV-ICC and conventional ICC, respectively. On PSM, patients with stone-ICC group had equivalent long-term outcomes as HBV-ICC patients. In contrast, on PSM, stone-ICC patients had a median overall survival of only 18.0 months versus 44.0 months for patients with conventional ICC. Median overall survival after intrahepatic-only recurrence among patients who had stone-ICC (6.0 months) was worse than OS among HBV-ICC (13.0 months) or conventional ICC (12.0 months) (p = 0.006 and p = 0.082, respectively). CONCLUSIONS While HBV-ICC had a better prognosis on unadjusted analyses, these differences were mitigated on PSM suggesting no stage-for-stage differences in outcomes compared with stone-ICC or conventional ICC. In contrast, patients with stone-ICC had worse long-term outcomes. These data highlight the relative importance of ICC etiology relative to established clinicopathological factors in the prognosis of patients with ICC.
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Affiliation(s)
- Xu-Feng Zhang
- Department of Hepatobiliary Surgery and Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.,Department of Surgery, The Ohio State University, Wexner Medical Center, 395 W. 12th Avenue, Suite 670, Columbus, OH, USA
| | - Jeffery Chakedis
- Department of Surgery, The Ohio State University, Wexner Medical Center, 395 W. 12th Avenue, Suite 670, Columbus, OH, USA
| | - Fabio Bagante
- Department of Surgery, University of Verona, Verona, Italy
| | - Eliza W Beal
- Department of Surgery, The Ohio State University, Wexner Medical Center, 395 W. 12th Avenue, Suite 670, Columbus, OH, USA
| | - Yi Lv
- Department of Hepatobiliary Surgery and Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Matthew Weiss
- Department of Surgery, Johns Hopkins Hospital, Baltimore, MD, USA
| | - Irinel Popescu
- Department of Surgery, Fundeni Clinical Institute, Bucharest, Romania
| | - Hugo P Marques
- Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal
| | | | | | - Carlo Pulitano
- Department of Surgery, Royal Prince Alfred Hospital, University of Sydney, Sydney, Australia
| | - Todd W Bauer
- Department of Surgery, University of Virginia, Charlottesville, VA, USA
| | - Feng Shen
- Department of Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai, China
| | | | - Oliver Soubrane
- Department of Hepatobiliopancreatic Surgery and Liver Transplantation, AP-HP, Beaujon Hospital, Clichy, France
| | - Guillaume Martel
- Division of General Surgery, Department of Surgery, University of Ottawa, Ottawa, ON, Canada
| | - B Groot Koerkamp
- Department of Surgery, Erasmus University Medical Centre, Rotterdam, Netherlands
| | | | - Endo Itaru
- Gastroenterological Surgery Division, Yokohama City University School of Medicine, Yokohama, Japan
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State University, Wexner Medical Center, 395 W. 12th Avenue, Suite 670, Columbus, OH, USA.
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He C, Zhang Y, Song Y, Wang J, Xing K, Lin X, Li S. Preoperative CEA levels are supplementary to CA19-9 levels in predicting prognosis in patients with resectable intrahepatic cholangiocarcinoma. J Cancer 2018; 9:3117-3128. [PMID: 30210635 PMCID: PMC6134824 DOI: 10.7150/jca.25339] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2018] [Accepted: 06/23/2018] [Indexed: 12/13/2022] Open
Abstract
Background: There are few diagnostic tools that can be used to determine which patient with intrahepatic cholangiocarcinoma (ICC) can benefit from surgery actually, highlighting that the need for new preoperative stratification strategies. The aim of this study was to investigate the predictive values of preoperative biomarkers in survival analyses for patients with ICC after surgical resection. Methods: A total of 285 patients with ICC were retrospectively reviewed. Receiver operating charateristics (ROC) curves were used to evaluate the predictive effects of preoperative carbohydrate antigen 19-9 (CA19-9) with different cutoff values and carcinoembryonic antigen (CEA) in patients with ICC. Results: Preoperative CA19-9 with a cutoff value of 200 U/ml performed better in predicting overall survival (OS) and progression free survival (PFS) in ICC patients. Patients with preoperative CA19-9 value > 200 U/ml generally had a poor surgical response. However, surgical resection could also benefit patients whose CA19-9 levels decreased postoperatively or preoperative CEA levels were negative. Conclusions: With the cutoff value of 200U/ml, CA19-9 was a better preoperative biomarker for predicting survival for ICC patients after surgical resection. Combination of preoperative CA19-9 and CEA showed the strongest predictive power in survival analyses in these patients and should be recognized in daily clinical care.
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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, Guangdong, 510060, P.R. China
| | - Yu Zhang
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong, 510060, P.R. 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, Guangdong, 510060, P.R. 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, Guangdong, 510060, P.R. China
| | - Kaili Xing
- 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, Guangdong, 510060, P.R. 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, Guangdong, 510060, P.R. 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, Guangdong, 510060, P.R. China
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24
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Zhu WF, Cheng LX, Li M, Zuo D, Zhang N, Zhuang HJ, Xie D, Zeng QD, Hutchison JA, Zhao YL. Frequency Shift Raman-Based Sensing of Serum MicroRNAs for Early Diagnosis and Discrimination of Primary Liver Cancers. Anal Chem 2018; 90:10144-10151. [DOI: 10.1021/acs.analchem.8b01798] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Affiliation(s)
- Wen-Feng Zhu
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, 19B Yuquan Road, Shijingshan District, Beijing 100049, China
| | - Lin-Xiu Cheng
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, 19B Yuquan Road, Shijingshan District, Beijing 100049, China
- CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, No. 11 Beiyitiao, Zhongguancun, Beijing 100190, China
- University of the Chinese Academy of Sciences, 19A Yuquan Road, Shijingshan District, Beijing 100049, P. R. China
| | - Min Li
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, 19B Yuquan Road, Shijingshan District, Beijing 100049, China
| | - Duo Zuo
- Department of Cancer Cell Biology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, China
| | - Ning Zhang
- Department of Cancer Cell Biology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, China
| | - Hong-Jun Zhuang
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, 19B Yuquan Road, Shijingshan District, Beijing 100049, China
| | - Dan Xie
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, 19B Yuquan Road, Shijingshan District, Beijing 100049, China
| | - Qing-Dao Zeng
- CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, No. 11 Beiyitiao, Zhongguancun, Beijing 100190, China
| | - James A. Hutchison
- School of Chemistry and Bio21 Institute, University of Melbourne, 30 Flemington Road, Parkville Victoria 3052 Australia
| | - Yu-Liang Zhao
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, 19B Yuquan Road, Shijingshan District, Beijing 100049, China
- CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, No. 11 Beiyitiao, Zhongguancun, Beijing 100190, China
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Lei Z, Xia Y, Si A, Wang K, Li J, Yan Z, Yang T, Wu D, Wan X, Zhou W, Liu J, Wang H, Cong W, Wu M, Pawlik TM, Lau WY, Shen F. Antiviral therapy improves survival in patients with HBV infection and intrahepatic cholangiocarcinoma undergoing liver resection. J Hepatol 2018; 68:655-662. [PMID: 29155069 DOI: 10.1016/j.jhep.2017.11.015] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2017] [Revised: 10/19/2017] [Accepted: 11/01/2017] [Indexed: 02/08/2023]
Abstract
BACKGROUND & AIMS The impact of hepatitis B virus (HBV) infection on outcomes after resection of intrahepatic cholangiocarcinoma (ICC) has not been reported. The aim of this study was to examine the impact of antiviral therapy on survival outcomes after liver resection for patients with ICC and underlying HBV infection. METHODS Data on 928 patients with ICC and HBV infection who underwent liver resection at two medical centers between 2006 and 2011 were analyzed. Data on viral reactivation, tumor recurrence, cancer-specific survival (CSS) and overall survival (OS) were obtained. Survival rates were analyzed using the time-dependent Cox regression model adjusted for potential covariates. RESULTS Postoperative viral reactivation occurred in 3.3%, 8.3% and 15.7% of patients who received preoperative antiviral therapy, who did not receive preoperative antiviral therapy with a low, or a high HBV-DNA level (< or ≥2,000 IU/ml), respectively (p <0.001). A high viral level and viral reactivation were independent risk factors of recurrence (hazard ratio [HR] 1.22 and 1.34), CSS (HR 1.36 and 1.46) and OS (HR1.23 and 1.36). Five-year recurrence, CSS and OS were better in patients who received antiviral therapy (70.5%, 46.9% and 43.0%) compared with patients who did not receive antiviral therapy and had a high viral level (86.5%, 20.9% and 20.5%, all p <0.001), respectively. The differences in recurrence, CSS and OS were minimal compared with no-antiviral therapy patients with a low viral level (71.7%, 35.5% and 33.5%, p = 0.057, 0.051 and 0.060, respectively). Compared to patients with a high viral level who received no antiviral therapy, patients who initiated antiviral therapy either before or after surgery had better long-term outcomes (HR 0.44 and 0.54 for recurrence; 0.38 and 0.57 for CSS; 0.46 and 0.54 for OS, respectively). CONCLUSIONS Viral reactivation was associated with worse prognoses after liver resection for HBV-infected patients with ICC. Antiviral therapy decreased viral reactivation and prolonged long-term survival for patients with ICC and a high viral level. LAY SUMMARY Postoperative hepatitis B virus reactivation was associated with an increased complication rate and a decreased survival rate after liver resection in patients with ICC and hepatitis B virus infection. Antiviral therapy before liver resection reduced the risk of postoperative viral reactivation. Both pre- and postoperative antiviral therapy was effective in prolonging patient survival.
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Affiliation(s)
- Zhengqing Lei
- Department of Hepatic Surgery IV, The Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Yong Xia
- Department of Hepatic Surgery IV, The Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Anfeng Si
- Department of Hepatic Surgery IV, The Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Kui Wang
- Department of Hepatic Surgery II, The Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
| | - Jun Li
- Department of Hepatic Surgery IV, The Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Zhenlin Yan
- Department of Hepatic Surgery IV, The Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Tian Yang
- Department of Hepatic Surgery IV, The Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Dong Wu
- Department of Hepatic Surgery I, The Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Xuying Wan
- Department of Chinese Traditional Medicine, The Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Weiping Zhou
- Department of Hepatic Surgery III, The Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Jingfeng Liu
- Department of Hepatobiliary Surgery, The Mengchao Hepatobiliary Surgery Hospital, Fujian Medical University, Fuzhou, China
| | - Hongyang Wang
- National Scientific Center for Liver Cancer, Shanghai, China
| | - Wenming Cong
- Department of Pathology, The Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Mengchao Wu
- Department of Hepatic Surgery IV, The Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China; National Scientific Center for Liver Cancer, Shanghai, China
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State University, Wexner Medical Center, Columbus, OH, USA
| | - Wan Yee Lau
- Department of Hepatic Surgery IV, The Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China; Faculty of Medicine, the Chinese University of Hong Kong, Shatin, Hong Kong, China
| | - Feng Shen
- Department of Hepatic Surgery IV, The Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
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Wang M, Gao Y, Feng H, Warner E, An M, Jia J, Chen S, Fang M, Ji J, Gu X, Gao C. A nomogram incorporating six easily obtained parameters to discriminate intrahepatic cholangiocarcinoma and hepatocellular carcinoma. Cancer Med 2018; 7:646-654. [PMID: 29473340 PMCID: PMC5852370 DOI: 10.1002/cam4.1341] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2017] [Revised: 11/10/2017] [Accepted: 12/21/2017] [Indexed: 12/15/2022] Open
Abstract
Intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) are the most prevalent histologic types of primary liver cancer (PLC). Although ICC and HCC share similar risk factors and clinical manifestations, ICC usually bears poorer prognosis than HCC. Confidently discriminating ICC and HCC before surgery is beneficial to both treatment and prognosis. Given the lack of effective differential diagnosis biomarkers and methods, construction of models based on available clinicopathological characteristics is in need. Nomograms present a simple and efficient way to make a discrimination. A total of 2894 patients who underwent surgery for PLC were collected. Of these, 1614 patients formed the training cohort for nomogram construction, and thereafter, 1280 patients formed the validation cohort to confirm the model's performance. Histopathologically confirmed ICC was diagnosed in 401 (24.8%) and 296 (23.1%) patients in these two cohorts, respectively. A nomogram integrating six easily obtained variables (Gender, Hepatitis B surface antigen, Aspartate aminotransferase, Alpha-fetoprotein, Carcinoembryonic antigen, Carbohydrate antigen 19-9) is proposed in accordance with Akaike's Information Criterion (AIC). A score of 15 was determined as the cut-off value, and the corresponding discrimination efficacy was sufficient. Additionally, patients who scored higher than 15 suffered poorer prognosis than those with lower scores, regardless of the subtype of PLC. A nomogram for clinical discrimination of ICC and HCC has been established, where a higher score indicates ICC and poor prognosis. Further application of this nomogram in multicenter investigations may confirm the practicality of this tool for future clinical use.
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Affiliation(s)
- Mengmeng Wang
- Department of Laboratory MedicineShanghai Eastern Hepatobiliary Surgery HospitalSecond Military Medical UniversityShanghai200438China
- Department of SurgeryUniversity of Michigan Medical SchoolAnn Arbor48109Michigan
| | - Yuzhen Gao
- Department of Laboratory MedicineShanghai Eastern Hepatobiliary Surgery HospitalSecond Military Medical UniversityShanghai200438China
| | - Huijuan Feng
- Department of Laboratory MedicineShanghai Eastern Hepatobiliary Surgery HospitalSecond Military Medical UniversityShanghai200438China
| | - Elisa Warner
- Department of SurgeryUniversity of Michigan Medical SchoolAnn Arbor48109Michigan
- Department of EpidemiologyUniversity of Michigan School of Public HealthAnn Arbor48109Michigan
| | - Mingrui An
- Department of SurgeryUniversity of Michigan Medical SchoolAnn Arbor48109Michigan
| | - Jian'an Jia
- Department of Laboratory MedicineShanghai Eastern Hepatobiliary Surgery HospitalSecond Military Medical UniversityShanghai200438China
| | - Shipeng Chen
- Department of Laboratory MedicineShanghai Eastern Hepatobiliary Surgery HospitalSecond Military Medical UniversityShanghai200438China
| | - Meng Fang
- Department of Laboratory MedicineShanghai Eastern Hepatobiliary Surgery HospitalSecond Military Medical UniversityShanghai200438China
| | - Jun Ji
- Department of Laboratory MedicineShanghai Eastern Hepatobiliary Surgery HospitalSecond Military Medical UniversityShanghai200438China
| | - Xing Gu
- Department of Laboratory MedicineShanghai Eastern Hepatobiliary Surgery HospitalSecond Military Medical UniversityShanghai200438China
| | - Chunfang Gao
- Department of Laboratory MedicineShanghai Eastern Hepatobiliary Surgery HospitalSecond Military Medical UniversityShanghai200438China
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Tian MX, He WJ, Liu WR, Yin JC, Jin L, Tang Z, Jiang XF, Wang H, Zhou PY, Tao CY, Ding ZB, Peng YF, Dai Z, Qiu SJ, Zhou J, Fan J, Shi YH. A Novel Risk prediction Model for Patients with Combined Hepatocellular-Cholangiocarcinoma. J Cancer 2018; 9:1025-1032. [PMID: 29581782 PMCID: PMC5868170 DOI: 10.7150/jca.23229] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2017] [Accepted: 01/28/2018] [Indexed: 12/20/2022] Open
Abstract
Backgrounds: Regarding the difficulty of CHC diagnosis and potential adverse outcomes or misuse of clinical therapies, an increasing number of patients have undergone liver transplantation, transcatheter arterial chemoembolization (TACE) or other treatments. Objective: To construct a convenient and reliable risk prediction model for identifying high-risk individuals with combined hepatocellular-cholangiocarcinoma (CHC). Methods: 3369 patients who underwent surgical resection for liver cancer at Zhongshan Hospital were enrolled in this study. The epidemiological and clinical characteristics of the patients were collected at the time of tumor diagnosis. Variables (P <0.25 in the univariate analyses) were evaluated using backward stepwise method. A receiver operating characteristic (ROC) curve was used to assess model discrimination. Calibration was performed using the Hosmer-Lemeshow test and a calibration curve. Internal validation was performed using a bootstrapping approach. Results: Among the entire study population, 250 patients (7.42%) were pathologically defined with CHC. Age, HBcAb, red blood cells (RBC), blood urea nitrogen (BUN), AFP, CEA and portal vein tumor thrombus (PVTT) were included in the final risk prediction model (area under the curve, 0.69; 95% confidence interval, 0.51-0.77). Bootstrapping validation presented negligible optimism. When the risk threshold of the prediction model was set at 20%, 2.73% of the patients diagnosed with liver cancer would be diagnosed definitely, which could identify CHC patients with 12.40% sensitivity, 98.04% specificity, and a positive predictive value of 33.70%. Conclusions: Herein, the study established a risk prediction model which incorporates the clinical risk predictors and CT/MRI-presented PVTT status that could be adopted to facilitate the diagnosis of CHC patients preoperatively.
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Affiliation(s)
- 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
| | - Wen-Jun He
- Department of Medical Statistic and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, 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
| | - Jia-Cheng Yin
- 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
| | - 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
| | - 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
| | - 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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28
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Zhang XF, Beal EW, Bagante F, Chakedis J, Weiss M, Popescu I, Marques HP, Aldrighetti L, Maithel SK, Pulitano C, Bauer TW, Shen F, Poultsides GA, Soubrane O, Martel G, Koerkamp BG, Itaru E, Pawlik TM. Early versus late recurrence of intrahepatic cholangiocarcinoma after resection with curative intent. Br J Surg 2017; 105:848-856. [PMID: 29193010 DOI: 10.1002/bjs.10676] [Citation(s) in RCA: 172] [Impact Index Per Article: 21.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2017] [Revised: 07/06/2017] [Accepted: 07/11/2017] [Indexed: 01/06/2023]
Abstract
BACKGROUND The objective of this study was to investigate the characteristics, treatment and prognosis of early versus late recurrence of intrahepatic cholangiocarcinoma (ICC) after hepatic resection. METHODS Patients who underwent resection with curative intent for ICC were identified from a multi-institutional database. Data on clinicopathological characteristics, initial operative details, timing and sites of recurrence, recurrence management and long-term outcomes were analysed. RESULTS A total of 933 patients were included. With a median follow-up of 22 months, 685 patients (73·4 per cent) experienced recurrence of ICC; 406 of these (59·3 per cent) developed only intrahepatic disease recurrence. The optimal cutoff value to differentiate early (540 patients, 78·8 per cent) versus late (145, 21·2 per cent) recurrence was defined as 24 months. Patients with early recurrence had extrahepatic disease more often (44·1 per cent versus 28·3 per cent in those with late recurrence; P < 0·001), whereas late recurrence was more often only intrahepatic (71·7 per cent versus 55·9 per cent for early recurrence; P < 0·001). From time of recurrence, overall survival was worse among patients who had early versus late recurrence (median 10 versus 18 months respectively; P = 0·029). In multivariable analysis, tumour characteristics including tumour size, number of lesions and satellite lesions were associated with an increased risk of early intrahepatic recurrence. In contrast, only the presence of liver cirrhosis was independently associated with an increased likelihood of late intrahepatic recurrence (hazard ratio 1·99, 95 per cent c.i. 1·11 to 3·56; P = 0·019). CONCLUSION Early and late recurrence after curative resection for ICC are associated with different risk factors and prognosis. Data on the timing of recurrence may inform decisions about the degree of postoperative surveillance, as well as help counsel patients with regard to their risk of recurrence.
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Affiliation(s)
- X-F Zhang
- Department of Hepatobiliary Surgery and Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.,Department of Surgery, The Ohio State University, Wexner Medical Center, Columbus, Ohio, USA
| | - E W Beal
- Department of Surgery, The Ohio State University, Wexner Medical Center, Columbus, Ohio, USA
| | - F Bagante
- Deparment of Surgery, University of Verona, Verona, Italy
| | - J Chakedis
- Department of Surgery, The Ohio State University, Wexner Medical Center, Columbus, Ohio, USA
| | - M Weiss
- Department of Surgery, Johns Hopkins Hospital, Baltimore, Maryland, USA
| | - I Popescu
- Department of Surgery, Fundeni Clinical Institute, Bucharest, Romania
| | - H P Marques
- Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal
| | - L Aldrighetti
- Department of Surgery, Ospedale San Raffaele, Milan, Italy
| | - S K Maithel
- Department of Surgery, Emory University, Atlanta, USA
| | - C Pulitano
- Department of Surgery, Royal Prince Alfred Hospital, University of Sydney, Sydney, New South Wales, Australia
| | - T W Bauer
- Department of Surgery, University of Virginia, Charlottesville, Virginia, USA
| | - F Shen
- Department of Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai, China
| | - G A Poultsides
- Department of Surgery, Stanford University, Stanford, California, USA
| | - O Soubrane
- Department of Hepatobiliopancreatic Surgery and Liver Transplantation, Assistance Publique - Hôpitaux de Paris, Beaujon Hospital, Clichy, France
| | - G Martel
- Division of General Surgery, Department of Surgery, University of Ottawa, Ottawa, Ontario, Canada
| | - B G Koerkamp
- Department of Surgery, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - E Itaru
- Gastroenterological Surgery Division, Yokohama City University School of Medicine, Yokohama, Japan
| | - T M Pawlik
- Department of Surgery, The Ohio State University, Wexner Medical Center, Columbus, Ohio, USA
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29
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Zhang XF, Bagante F, Chakedis J, Moris D, Beal EW, Weiss M, Popescu I, Marques HP, Aldrighetti L, Maithel SK, Pulitano C, Bauer TW, Shen F, Poultsides GA, Soubrane O, Martel G, Groot Koerkamp B, Guglielmi A, Itaru E, Pawlik TM. Perioperative and Long-Term Outcome for Intrahepatic Cholangiocarcinoma: Impact of Major Versus Minor Hepatectomy. J Gastrointest Surg 2017; 21:1841-1850. [PMID: 28744741 DOI: 10.1007/s11605-017-3499-6] [Citation(s) in RCA: 57] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2017] [Accepted: 07/06/2017] [Indexed: 01/31/2023]
Abstract
BACKGROUND The objective of the current study was to investigate both short- and long-term outcomes of patients undergoing curative-intent resection for intrahepatic cholangiocarcinoma (ICC) stratified by extent of hepatic resection relative to overall final pathological margin status. METHODS One thousand twenty-three patients with ICC who underwent curative-intent resection were identified from a multi-institutional database. Demographic, clinicopathological, and operative data, as well as overall (OS) and recurrence-free survival (RFS) were compared among patients undergoing major and minor resection before and after propensity score matching. RESULTS Overall, 608 (59.4%) patients underwent major hepatectomy, while 415 (40.6%) had a minor resection. Major hepatectomy was more frequently performed among patients who had large, multiple, and bilobar tumors. Roughly half of patients (n = 294, 48.4%) developed a postoperative complication following major hepatectomy versus only one fourth of patients (n = 113, 27.2%) after minor resection (p < 0.001). In the propensity model, patients who underwent major hepatectomy had an equivalent OS and RFS versus patients who had a minor hepatectomy (median OS, 38 vs. 37 months, p = 0.556; and median RFS, 20 vs. 18 months, p = 0.635). Patients undergoing major resection had comparable OS and RFS with wide surgical margin (≥10 and 5-9 mm), but improved RFS when surgical margin was narrow (1-4 mm) versus minor resection in the propensity model. In the Cox regression model, tumor characteristics and surgical margin were independently associated with long-term outcome. CONCLUSIONS Major hepatectomy for ICC was not associated with an overall survival benefit, yet was associated with increased perioperative morbidity. Margin width, rather than the extent of resection, affected long-term outcomes. Radical parenchymal-sparing resection should be advocated if a margin clearance of ≥5 mm can be achieved.
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Affiliation(s)
- Xu-Feng Zhang
- Department of Hepatobiliary Surgery and Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
- Department of Surgery, The Ohio State University Wexner Medical Center, 395 W. 12th Ave., Suite, Columbus, OH, 670, USA
| | - Fabio Bagante
- Department of Surgery, Johns Hopkins Hospital, Baltimore, MD, USA
| | - Jeffery Chakedis
- Department of Surgery, The Ohio State University Wexner Medical Center, 395 W. 12th Ave., Suite, Columbus, OH, 670, USA
| | - Dimitrios Moris
- Department of Surgery, The Ohio State University Wexner Medical Center, 395 W. 12th Ave., Suite, Columbus, OH, 670, USA
| | - Eliza W Beal
- Department of Surgery, The Ohio State University Wexner Medical Center, 395 W. 12th Ave., Suite, Columbus, OH, 670, USA
| | - Matthew Weiss
- Department of Surgery, Johns Hopkins Hospital, Baltimore, MD, USA
| | - Irinel Popescu
- Department of Surgery, Fundeni Clinical Institute, Bucharest, Romania
| | - Hugo P Marques
- Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal
| | | | | | - Carlo Pulitano
- Department of Surgery, Royal Prince Alfred Hospital, University of Sydney, Sydney, Australia
| | - Todd W Bauer
- Department of Surgery, University of Virginia, Charlottesville, VA, USA
| | - Feng Shen
- Department of Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai, China
| | | | - Oliver Soubrane
- Department of Hepatobiliopancreatic Surgery and Liver Transplantation, AP-HP, Beaujon Hospital, Clichy, France
| | - Guillaume Martel
- Division of General Surgery, Department of Surgery, University of Ottawa, Ottawa, ON, Canada
| | - B Groot Koerkamp
- Department of Surgery, Erasmus University Medical Centre, Rotterdam, Netherlands
| | - Alfredo Guglielmi
- Department of Surgery, The Ohio State University Wexner Medical Center, 395 W. 12th Ave., Suite, Columbus, OH, 670, USA
| | - Endo Itaru
- Gastroenterological Surgery Division, Yokohama City University School of Medicine, Yokohama, Japan
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center, 395 W. 12th Ave., Suite, Columbus, OH, 670, USA.
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30
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Berretta M, Cavaliere C, Alessandrini L, Stanzione B, Facchini G, Balestreri L, Perin T, Canzonieri V. Serum and tissue markers in hepatocellular carcinoma and cholangiocarcinoma: clinical and prognostic implications. Oncotarget 2017; 8:14192-14220. [PMID: 28077782 PMCID: PMC5355172 DOI: 10.18632/oncotarget.13929] [Citation(s) in RCA: 51] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2016] [Accepted: 10/28/2016] [Indexed: 12/12/2022] Open
Abstract
HCC represents the sixth most common cancer worldwide and the second leading cause of cancer-related death. Despite the high incidence, treatment options for advanced HCC remain limited and unsuccessful, resulting in a poor prognosis. Despite the major advances achieved in the diagnostic management of HCC, only one third of the newly diagnosed patients are presently eligible for curative treatments. Advances in technology and an increased understanding of HCC biology have led to the discovery of novel biomarkers. Improving our knowledge about serum and tissutal markers could ultimately lead to an early diagnosis and better and early treatment strategies for this deadly disease. Serum biomarkers are striking potential tools for surveillance and early diagnosis of HCC thanks to the non-invasive, objective, and reproducible assessments they potentially enable. To date, many biomarkers have been proposed in the diagnosis of HCC. Cholangiocarcinoma (CCA) is an aggressive malignancy, characterized by early lymph node involvement and distant metastasis, with 5-year survival rates of 5%-10%. The identification of new biomarkers with diagnostic, prognostic or predictive value is especially important as resection (by surgery or combined with a liver transplant) has shown promising results and novel therapies are emerging. However, the relatively low incidence of CCA, high frequency of co-existing cholestasis or cholangitis (primary sclerosing cholangitis –PSC- above all), and difficulties with obtaining adequate samples, despite advances in sampling techniques and in endoscopic visualization of the bile ducts, have complicated the search for accurate biomarkers. In this review, we attempt to analyze the existing literature on this argument.
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Affiliation(s)
| | - Carla Cavaliere
- Department of Onco-Ematology Medical Oncology, S.G. Moscati Hospital of Taranto Taranto, Italy
| | - Lara Alessandrini
- Division of Pathology, National Cancer Institute, Aviano (PN), Italy
| | - Brigida Stanzione
- Department of Medical Oncology, National Cancer Institute, Aviano (PN), Italy
| | - Gaetano Facchini
- Department of Medical Oncology, National Cancer Institute, "G. Pascale" Foundation, Naples, Italy
| | - Luca Balestreri
- Department of Radiology, National Cancer Institute, Aviano (PN), Italy
| | - Tiziana Perin
- Division of Pathology, National Cancer Institute, Aviano (PN), Italy
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31
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Zhou Y, Wu L, Xu D, Wan T, Si X. A pooled analysis of combined liver and inferior vena cava resection for hepatic malignancy. HPB (Oxford) 2017. [PMID: 28645571 DOI: 10.1016/j.hpb.2017.05.008] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Limited data are currently available to address the safety and efficacy of combined resection of the liver and inferior vena cava (IVC) for hepatic malignancies. METHODS A systematic review was performed to identify relevant studies. Pooled individual data were examined for the clinical outcome of combined resection of the liver and IVC for hepatic malignancies. RESULTS A total of 258 patients were described in 38 articles eligible for inclusion. Resections were performed for colorectal liver metastasis (CLM) [n = 128 (50%)], intrahepatic cholangiocarcinoma (ICC) [n = 51 (20%)], hepatocellular carcinoma (HCC) [n = 48 (19%)], and other pathologies [n = 31 (11%)]. There were 14 (5%) perioperative deaths. The median survival duration was 34 months, and the 1-, 3- and 5-year overall survival (OS) rate was 79%, 46% and 33%, respectively. The 5-year OS rate was 26% for CLM, 37% for ICC, and 30% for HCC. CONCLUSION Combined resection of the liver and IVC for hepatic malignancies is safe and applicable, and offers acceptable survival outcomes.
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Affiliation(s)
- Yanming Zhou
- Department of Hepatobiliary & Pancreatovascular Surgery, First Affiliated Hospital of Xiamen University, Xiamen, China.
| | - Lupeng Wu
- Department of Hepatobiliary & Pancreatovascular Surgery, First Affiliated Hospital of Xiamen University, Xiamen, China
| | - Dong Xu
- Department of Hepatobiliary & Pancreatovascular Surgery, First Affiliated Hospital of Xiamen University, Xiamen, China
| | - Tao Wan
- Department of Hepatobiliary & Pancreatovascular Surgery, First Affiliated Hospital of Xiamen University, Xiamen, China
| | - Xiaoying Si
- Department of Hepatobiliary & Pancreatovascular Surgery, First Affiliated Hospital of Xiamen University, Xiamen, China
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32
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Yuan L, Luo X, Lu X, Yi B, Chu K, Cai Q, Jiang X. Comparison of clinicopathological characteristics between cirrhotic and non-cirrhotic patients with intrahepatic cholangiocarcinoma: A large-scale retrospective study. Mol Clin Oncol 2017; 7:615-622. [PMID: 29046795 DOI: 10.3892/mco.2017.1387] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2016] [Accepted: 07/22/2017] [Indexed: 12/22/2022] Open
Abstract
The effect of cirrhosis on the characteristics of intrahepatic cholangiocarcinoma (ICC) has not been fully elucidated. The purpose of this study was to investigate how cirrhosis affects the clinicopathological characteristics and survival of surgically treated ICC patients. A total of 1,312 ICC patients surgically treated between January 2007 and December 2011 at a single institution were retrospectively reviewed and the clinicopathological data were compared between cirrhotic and non-cirrhotic patients. Univariate and multivariate analyses were performed to identify significant and independent prognostic factors in this cohort. A total of 302 patients (23.0%) were cirrhotic. Compared with cirrhotic patients, the tumors in non-cirrhotic patients were usually larger, less differentiated, and more likely to have lymphatic metastasis, vascular and perineural invasion. Following resection, cirrhotic patients achieved a longer survival compared with non-cirrhotic patients (16.0 vs. 13.0 months, respectively; P<0.038). Multivariate analysis demonstrated that hepatitis B virus infection and cirrhosis were independent favorable prognostic factors, while the presence of cholelithiasis, elevated carbohydrate antigen 19-9 and carcinoembryonic antigen levels, multiple tumors, lymphatic metastasis, vascular invasion and positive surgical margin status were independent unfavorable prognostic factors. Overall, the clinicopathological characteristics of ICC patients with and without cirrhosis differed significantly. Compared with cirrhotic patients, in whom the biological behavior of ICC was similar to that of HCC, non-cirrhotic patients exhibited higher-risk pathological characteristics, lower curative resection rate and worse survival.
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Affiliation(s)
- Lei Yuan
- The First Department of Biliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, P.R. China
| | - Xianwu Luo
- The First Department of Biliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, P.R. China
| | - Xinyuan Lu
- Department of Pathology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, P.R. China
| | - Bin Yi
- The First Department of Biliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, P.R. China
| | - Kaijian Chu
- The First Department of Biliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, P.R. China
| | - Quanyu Cai
- Department of Medical Imaging, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, P.R. China
| | - Xiaoqing Jiang
- The First Department of Biliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, P.R. China
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33
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Ahmed Mohammed HF, Roberts LR. Should AFP (or any biomarkers) be used for HCC surveillance? CURRENT HEPATOLOGY REPORTS 2017; 16:137-145. [PMID: 29085770 PMCID: PMC5659201 DOI: 10.1007/s11901-017-0349-7] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
A PURPOSE OF REVIEW To address the controversy around the use of biomarkers for hepatocellular carcinoma (HCC) surveillance in individuals with cirrhosis or chronic hepatitis B who are at risk for development of liver cancer. B RECENT FINDINGS Recent studies suggest that surveillance for hepatocellular carcinoma is beneficial, even after adjustment for lead time and other biases. Alpha fetoprotein (AFP) is complementary to ultrasound (US) in surveillance, particularly in obese patients and patients with infiltrative tumors. US and AFP are both associated with harms to patients from false positive over-diagnosis, with US appearing to cause greater harms. Including patient demographic characteristics and additional biomarkers into diagnostic models is beneficial. Recent studies emphasize the advantage of time trends in biomarkers over single cross-sectional measurements. C SUMMARY AFP and other biomarkers are complementary to US in surveillance for HCC, especially when applied in models including patient variables and incorporating time trends in biomarker levels. With advances in genetic and molecular analysis of tumors, we may be poised at the cusp of a revolution in HCC surveillance.
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Affiliation(s)
| | - Lewis R Roberts
- Department of Pediatrics, University of Minnesota School of Medicine, Minneapolis, MN
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34
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Kuang J, Li QY, Fan F, Shen NJ, Zhan YJ, Tang ZH, Yu WL. Overexpression of the X-linked ribosomal protein S4 predicts poor prognosis in patients with intrahepatic cholangiocarcinoma. Oncol Lett 2017; 14:41-46. [PMID: 28693133 PMCID: PMC5494819 DOI: 10.3892/ol.2017.6137] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2015] [Accepted: 01/11/2017] [Indexed: 12/27/2022] Open
Abstract
X-linked ribosomal protein S4 (RPS4X) has previously been reported to be associated with cisplatin resistance and clinical outcome in bladder and ovarian cancer. However, the value of RPS4X as a diagnostic and prognostic marker in intrahepatic cholangiocarcinoma (ICC) has not yet been investigated. The present study evaluated the expression pattern, and diagnostic and prognostic value of RPS4X in patients with ICC. Retrospective analysis was performed for a total of 201 patients with intrahepatic cholangiocarcinoma, and 8 patients with inflammation of the bile duct. Immunohistochemistry was performed using tissue microarrays to characterize the expression profile of RPS4X. Receiver operating characteristic (ROC) curves, the Kaplan-Meier estimator and Cox regression analysis were applied to evaluate the potential diagnostic and prognostic value of RPS4X in ICC. RPS4X was significantly upregulated in ICC tissues compared with the inflamed bile duct tissues. When differentiating ICC from normal controls, ROC analysis of RPS4X gave an area under the curve value of 0.9030 (sensitivity, 82.59%; specificity, 100%). RPS4X expression was significantly positively correlated with serum alkaline phosphatase levels. Survival analysis demonstrated that RPS4X expression levels were an independent prognostic factor for overall survival. Therefore, RPS4X expression levels may serve as a novel diagnostic and prognostic marker in ICC.
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Affiliation(s)
- Jie Kuang
- Department of Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China
| | - Qin-Yu Li
- Department of Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China
| | - Fei Fan
- Department II of Biliary Tract Surgery, Eastern Hepatobiliary Hospital, Shanghai 200438, P.R. China
| | - Ning-Jia Shen
- Department II of Biliary Tract Surgery, Eastern Hepatobiliary Hospital, Shanghai 200438, P.R. China
| | - Yong-Jie Zhan
- Department II of Biliary Tract Surgery, Eastern Hepatobiliary Hospital, Shanghai 200438, P.R. China
| | - Zhao-Hui Tang
- Department of General Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China
| | - Wen-Long Yu
- Department II of Biliary Tract Surgery, Eastern Hepatobiliary Hospital, Shanghai 200438, P.R. China
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35
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Liang Z, Liu X, Zhang Q, Wang C, Zhao Y. Diagnostic value of microRNAs as biomarkers for cholangiocarcinoma. Dig Liver Dis 2016; 48:1227-32. [PMID: 27476468 DOI: 10.1016/j.dld.2016.07.006] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2016] [Revised: 07/06/2016] [Accepted: 07/06/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND It has been reported that microRNAs might serve as biomarkers for cholangiocarcinoma (CCA) detection, but their diagnostic accuracy are unclear and controversial. AIM To evaluate the diagnostic accuracy of microRNAs for CCA. MATERIALS AND METHODS PubMed, Embase, Web of Science and Cochrane Library were systematically searched to identify relevant articles by using the key words "cholangiocarcinoma" and "microRNA". The methodological quality of each study was assessed by QUADAS-2. According to the inclusive and exclusive criteria, 11 articles were identified and analyzed by Meta-disc software v.1.4 and STATA 12.0 software package. RESULTS 11 articles with 430 CCA patients and 406 controls were identified. The results showed that the pooled sensitivity was 0.756 (95% CI: 0.693-0.810), specificity was 0.914 (95% CI: 0.861-0.947), positive likelihood ratio was 8.747 (95% CI: 5.320-14.381), negative likelihood ratio was 0.267 (95% CI: 0.208-0.341) and diagnostic odds ratio was 32.791 (95% CI: 17.327, 62.060). In addition, the area under the summary ROC cure (AUC) was 0.90 (95% CI: 0.87-0.93). CONCLUSION MicroRNAs have great potential as biomarkers for the diagnosis of CCA patients. However, the clinical application of microRNA assays for CCA diagnosis still needs further validation by more prospective studies.
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Affiliation(s)
- Zhenzhen Liang
- Dept. Epidemiology and Statistics, School of Public Health, Jilin University, Changchun, Jilin, China
| | - Xin Liu
- Dept. Epidemiology and Statistics, School of Public Health, Jilin University, Changchun, Jilin, China
| | - Qian Zhang
- Dept. Epidemiology and Statistics, School of Public Health, Jilin University, Changchun, Jilin, China
| | - Chunpeng Wang
- School of Mathematics and Statistics, Northeast Normal University, Changchun, Jilin, China.
| | - Yinlong Zhao
- Dept. Nuclear Medicine, 2nd Hospital, Jilin University, Changchun, China.
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36
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Yuan L, Luo X, Lu X, Huang B, Cai Q. Liver resection for intrahepatic cholangiocarcinoma in AJCC‑stage Ⅳ: An evaluation of the survival benefit and prognostic accuracy of current AJCC staging system on N and M classification. Oncol Rep 2016; 36:2663-2672. [PMID: 27666632 DOI: 10.3892/or.2016.5103] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2016] [Accepted: 07/01/2016] [Indexed: 11/06/2022] Open
Abstract
Intrahepatic cholangiocarcinoma (ICC) is usually confirmed in advanced stage at the time of diagnosis or after surgical exploration, however, indication of surgical treatment is usually controversial for ICC in advanced stages. This retrospective study aims to evaluate clinical value of surgery for such tumors, in order to identify the appropriate patients who will benefit from surgery, and to evaluate the prognostic accuracy of the current staging system for advanced ICC. From January 2007 to December 2011, 387 consecutive surgically treated patients with ICC in AJCC‑stage Ⅳ were evaluated. Survival was compared among different patients grouped by different elements of AJCC staging system. The prognostic importance of extent of lymph node (LN) metastasis relative to the AJCC N and M classification system was assessed. Our data showed that survival was much better for patients in AJCC‑stage ⅣA group (median survival time, MST, 9.0 months) than in AJCC‑stage ⅣB group (MST, 5.0 months) (P<0.001). While in AJCC‑stage ⅣB group, survival for patients in AnyTN2‑3M0 subgroup (MST, 9.0 months) was much better than in AnyTN0M1 subgroup (MST, 3.0 months); and better than in AnyTN2‑3M1 subgroup (MST, 4.0 months) (P<0.001). Overall, R0 and R1 liver resection should be indicated for patients in AJCC‑stage ⅣA group and AnyTN2‑3M0 subgroup in AJCC‑stage ⅣB group, as patients in these groups will benefit from surgery with relatively better survival. Staging of advanced ICC by N2‑3 instead of M1 for extended LN metastasis classification is superior in comparison with the AJCC staging system.
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Affiliation(s)
- Lei Yuan
- The First Department of Biliary Surgery, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, P.R. China
| | - Xianwu Luo
- The First Department of Biliary Surgery, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, P.R. China
| | - Xinyuan Lu
- Department of Pathology, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, P.R. China
| | - Bin Huang
- Department of Medical Imaging, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, P.R. China
| | - Quanyu Cai
- Department of Medical Imaging, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, P.R. China
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Hao XY, Cai JP, Liu X, Chen W, Hou X, Chen D, Lai JM, Liang LJ, Yin XY. EYA4 gene functions as a prognostic marker and inhibits the growth of intrahepatic cholangiocarcinoma. CHINESE JOURNAL OF CANCER 2016; 35:70. [PMID: 27469137 PMCID: PMC4966169 DOI: 10.1186/s40880-016-0133-z] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/07/2016] [Accepted: 07/19/2016] [Indexed: 02/08/2023]
Abstract
Background The molecular prognostic markers and carcinogenesis of intrahepatic cholangiocarcinoma (ICC) have not been well documented. The purpose of this study was to investigate the prognostic value of the eyes absent homolog 4 (EYA4) gene in ICC and its biological effects on ICC growth in vitro and in vivo. Methods One hundred twelve patients with ICC who underwent hepatectomy were enrolled in the study. EYA4 mRNA and EYA4 protein levels in ICC and adjacent non-tumoral tissues were evaluated using real-time quantitative polymerase chain reaction and immunohistochemical staining, respectively. EYA4 protein levels in ICC cells were determined using western blot analysis. The associations between EYA4 expression and clinicopathologic features of ICC were analyzed. To identify independent prognostic factors, univariate and multivariate analyses were performed. The biological effects of EYA4 on ICC cells were evaluated by establishing stable EYA4-overexpressing transfectants in vitro, and EYA4’s effects on tumor growth were evaluated by intra-tumoral injection of EYA4-expressing plasmids in a NOD/SCID murine model of xenograft tumors. Results ICC tissues had significantly lower EYA4 mRNA and protein levels compared with adjacent non-tumoral tissues (both P < 0.001). Univariate and multivariate analyses showed that EYA4 protein level, tumor number, adjacent organ invasion, lymph node metastasis, and tumor differentiation were independent prognostic factors for disease-free survival and overall survival (all P < 0.05). In vitro, EYA4 overexpression inhibited tumor cell growth, foci formation, and cell invasiveness. In vivo, intra-tumoral injection of EYA4-expressing plasmids significantly inhibited ICC growth in the murine xenograft model compared with the control group (P < 0.05). Conclusion EYA4 gene functioned as a molecular prognostic marker in ICC, and its overexpression inhibited tumor growth in vitro and in vivo.
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Affiliation(s)
- Xiao-Yi Hao
- Departments of Pancreatobiliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, Zhongshan 2nd Road, Guangzhou, 510080, Guangdong, P. R. China
| | - Jian-Peng Cai
- Departments of Pancreatobiliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, Zhongshan 2nd Road, Guangzhou, 510080, Guangdong, P. R. China
| | - Xin Liu
- Departments of Pancreatobiliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, Zhongshan 2nd Road, Guangzhou, 510080, Guangdong, P. R. China
| | - Wei Chen
- Departments of Pancreatobiliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, Zhongshan 2nd Road, Guangzhou, 510080, Guangdong, P. R. China
| | - Xun Hou
- Departments of Pancreatobiliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, Zhongshan 2nd Road, Guangzhou, 510080, Guangdong, P. R. China
| | - Dong Chen
- Departments of Pancreatobiliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, Zhongshan 2nd Road, Guangzhou, 510080, Guangdong, P. R. China
| | - Jia-Ming Lai
- Departments of Pancreatobiliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, Zhongshan 2nd Road, Guangzhou, 510080, Guangdong, P. R. China
| | - Li-Jian Liang
- Departments of Pancreatobiliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, Zhongshan 2nd Road, Guangzhou, 510080, Guangdong, P. R. China
| | - Xiao-Yu Yin
- Departments of Pancreatobiliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, Zhongshan 2nd Road, Guangzhou, 510080, Guangdong, P. R. China.
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Song P, Tang Q, Feng X, Tang W. Biomarkers: evaluation of clinical utility in surveillance and early diagnosis for hepatocellular carcinoma. Scand J Clin Lab Invest Suppl 2016; 245:S70-6. [PMID: 27438343 DOI: 10.1080/00365513.2016.1210328] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second most common cause of death from cancer worldwide. Strategies to surveil and diagnose HCC in an earlier stage are urgently needed since this is when curable interventions can be offered to achieve long-term disease-free survival. Over the past few decades, research has suggested measuring alpha-fetoprotein (AFP) concentration and performing abdominal ultrasound (US) as part of routine surveillance of HCC every 6 months for high-risk patients, and many HCC guidelines worldwide have also recommended these examinations. Over the past 5 years, however, the role of serum biomarkers in HCC surveillance and diagnosis has diminished due to advances in imaging modalities. AFP was excluded from the surveillance and/or diagnostic criteria in the HCC guidelines published by some Western countries. In Asian countries, serum biomarkers such as AFP, the Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), and des-γ-carboxyprothrombin (DCP) are still recommended for HCC surveillance and are being used as an adjunctive diagnostic tool in accordance with HCC guidelines. Moreover, novel biomarkers including Dickkopf-1 (DKK1), midkine (MDK), and microRNA (miRNA) are being studied in this regard. China accounts for 50% of HCC cases worldwide, so identifying biomarkers of HCC is paramount. Recent studies have indicated the clinical utility of simultaneous measurement of AFP and DCP for the early detection of HCC in China. They are predominantly used for cases caused by HBV infection. Additional large-scale prospective studies should be conducted to establish the utility of these biomarkers.
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Affiliation(s)
- Peipei Song
- a Department of Human and Engineered Environmental Studies, Graduate School of Frontier Sciences , The University of Tokyo , Kashiwa-Shi , Chiba , Japan ;,b Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine , The University of Tokyo , Tokyo , Japan
| | - Qi Tang
- b Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine , The University of Tokyo , Tokyo , Japan
| | - Xiaobin Feng
- c Department of Hepatobiliary Surgery, Southwest Hospital , Third Military Medical University , Chongqing , China
| | - Wei Tang
- b Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine , The University of Tokyo , Tokyo , Japan ;,c Department of Hepatobiliary Surgery, Southwest Hospital , Third Military Medical University , Chongqing , China
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Zhao YJ, Chen WX, Wu DS, Zhang WY, Zheng LR. Differentiation of mass-forming intrahepatic cholangiocarcinoma from poorly differentiated hepatocellular carcinoma: based on the multivariate analysis of contrast-enhanced computed tomography findings. Abdom Radiol (NY) 2016; 41:978-89. [PMID: 27193795 DOI: 10.1007/s00261-015-0629-z] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
PURPOSE We aim to gain further insight into identifying differential radiological features of mass-forming intrahepatic cholangiocarcinoma (mICC) from poorly differentiated hepatocellular carcinoma (pHCC) on contrast-enhanced computed tomography (CT). MATERIALS AND METHODS 107 patients with pathologically confirmed mICC (n = 48) and pHCC (n = 59) who had undergone preoperative contrast-enhanced CT were enrolled. Qualitative analysis of CT images were evaluated for tumor demarcation, shape, presence of satellite nodules, capsular retraction, biliary involvement, intratumoral arteries, tortuous tumoral vessels, vascular invasion, portal vein tumor thrombus, arterial enhancement pattern, portal venous phase enhancement, and washout pattern. Quantitative analysis was performed for mean attenuation of tumor and tumor-to-liver contrast during each phase. The degree of arterial enhancement was graded based on quantitative measurements. RESULTS A lobulated shape, indistinct margin, peripheral rim enhancement in the arterial phase, and the presence of bile duct dilatation were CT features favoring mICC, whereas a round shape, partially indistinct margin, heterogeneous enhancement in the arterial phase, washout pattern and the presence of tortuous tumoral vessels were CT features favoring pHCC in the univariate analysis (P < 0.05). Tumor-to-liver contrast of pHCC was greater than that of mICC during the arterial phase (P = 0.015). In the multivariate analysis, bile duct dilatation, tortuous tumoral vessels, and a washout pattern were independent CT features for distinguishing between the two types. (P = 0.003, P = 0.003, P = 0.044, respectively). CONCLUSION The absence of a washout pattern and tortuous tumoral vessels and presence of bile duct dilatation are more indicative of mICC than of pHCC on contrast-enhanced CT.
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Affiliation(s)
- Yi-Jun Zhao
- Department of Radiology, West China Hospital of Sichuan University, NO. 37, Guoxue Alley, Chengdu, 610041, Sichuan, China
| | - Wei-Xia Chen
- Department of Radiology, West China Hospital of Sichuan University, NO. 37, Guoxue Alley, Chengdu, 610041, Sichuan, China.
| | - Dong-Sheng Wu
- Department of Radiology, No. 4 West China Hospital of Sichuan University, NO. 18, South Renmin Road, Chengdu, Sichuan, China
| | - Wen-Yan Zhang
- Department of Pathology, West China Hospital of Sichuan University, NO. 37, Guoxue Alley, Chengdu, Sichuan, China
| | - Li-Rong Zheng
- Department of Radiology, West China Hospital of Sichuan University, NO. 37, Guoxue Alley, Chengdu, 610041, Sichuan, China
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Wang LJ, He CC, Sui X, Cai MJ, Zhou CY, Ma JL, Wu L, Wang H, Han SX, Zhu Q. MiR-21 promotes intrahepatic cholangiocarcinoma proliferation and growth in vitro and in vivo by targeting PTPN14 and PTEN. Oncotarget 2016; 6:5932-46. [PMID: 25803229 PMCID: PMC4467412 DOI: 10.18632/oncotarget.3465] [Citation(s) in RCA: 90] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2014] [Accepted: 01/20/2015] [Indexed: 12/27/2022] Open
Abstract
Intrahepatic cholangiocarcinoma (ICC) constitutes the second-most common primary hepatic malignancy. MicroRNAs (miRNAs) play important roles in the pathogenesis of ICC. However, the clinical significance of miR-21 levels in ICC remains unclear. Here, we investigated the role of miR-21 in ICC and found that its expression was significantly upregulated in serum of ICC patients. Serum miR-21 levels robustly distinguished ICC patients from control subjects. Further experiments showed that inhibition of miR-21 suppressed ICC cell proliferation in vitro and tumor growth in vivo. Specifically, inhibition of miR-21 induced cell cycle arrest and apoptosis. Moreover, PTPN14 and PTEN were identified as direct and functional targets of miR-21. Finally, we showed high expression levels of miR-21 were closely related to adverse clinical features, diminished survival, and poor prognosis in ICC patients. This study revealed functional and mechanistic links between miR-21 and tumor suppressor genes, PTPN14 and PTEN, in the pathogenesis of ICC. MiR-21 not only plays important roles in the regulation of cell proliferation and tumor growth in ICC, but is also a diagnostic and prognostic marker, and a potential therapeutic target for ICC.
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Affiliation(s)
- Li-Juan Wang
- Department of Oncology, the First Affiliated Hospital of Medical school of Xi'an Jiaotong University, Xi'an, Shaanxi Province, P.R. China
| | - Chen-Chen He
- Department of Oncology, the First Affiliated Hospital of Medical school of Xi'an Jiaotong University, Xi'an, Shaanxi Province, P.R. China
| | - Xin Sui
- Department of Oncology, the First Affiliated Hospital of Medical school of Xi'an Jiaotong University, Xi'an, Shaanxi Province, P.R. China
| | - Meng-Jiao Cai
- Department of Oncology, the First Affiliated Hospital of Medical school of Xi'an Jiaotong University, Xi'an, Shaanxi Province, P.R. China
| | - Cong-Ya Zhou
- Department of Oncology, the First Affiliated Hospital of Medical school of Xi'an Jiaotong University, Xi'an, Shaanxi Province, P.R. China
| | - Jin-Lu Ma
- Department of Oncology, the First Affiliated Hospital of Medical school of Xi'an Jiaotong University, Xi'an, Shaanxi Province, P.R. China
| | - Lei Wu
- Department of Oncology, the First Affiliated Hospital of Medical school of Xi'an Jiaotong University, Xi'an, Shaanxi Province, P.R. China.,Center of Radiotherapy, Shaanxi Provincial Tumor Hospital, Shaanxi Province, P.R. China
| | - Hao Wang
- Department of Oncology, the First Affiliated Hospital of Medical school of Xi'an Jiaotong University, Xi'an, Shaanxi Province, P.R. China.,Center of Radiotherapy, Shaanxi Provincial Tumor Hospital, Shaanxi Province, P.R. China
| | - Su-Xia Han
- Department of Oncology, the First Affiliated Hospital of Medical school of Xi'an Jiaotong University, Xi'an, Shaanxi Province, P.R. China
| | - Qing Zhu
- Department of Oncology, the First Affiliated Hospital of Medical school of Xi'an Jiaotong University, Xi'an, Shaanxi Province, P.R. China
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Joo I, Lee JM. Recent Advances in the Imaging Diagnosis of Hepatocellular Carcinoma: Value of Gadoxetic Acid-Enhanced MRI. Liver Cancer 2016; 5:67-87. [PMID: 26989660 PMCID: PMC4789886 DOI: 10.1159/000367750] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Magnetic resonance imaging (MRI) using gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DPTA), or gadoxetic acid for short, is a hepatocyte-specific contrast agent which is now increasingly used for the detection and characterization of focal hepatic lesions, particularly in patients at high-risk of developing hepatocellular carcinomas (HCC). In fact, several recent guidelines now recognize gadoxetic acid-enhanced MRI (Gd-EOB-MRI) as the primary diagnostic imaging modality for the noninvasive diagnosis of HCC, although it must be noted that several major guidelines still include only extracellular contrast media-enhanced computed tomography and MRI. The primary merits of Gd-EOB-MRI lie in the fact that it can provide not only dynamic imaging, but also hepatobiliary phase (HBP) imaging which can lead to high lesion-to-liver contrast and give additional information regarding hepatocyte uptake via organic anion transporting polypeptides. This, in turn, allows higher sensitivity in detecting small HCCs and helps provide additional information regarding the multistep process of hepatocarcinogenesis. Indeed, many recent studies have investigated the diagnostic value of Gd-EOB-MRI for early HCCs as well as its role as a potential imaging biomarker in predicting outcome. We herein review the recent advances in the imaging diagnosis of HCCs focusing on the applications of Gd-EOB-MRI and the challenging issues that remain.
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Affiliation(s)
- Ijin Joo
- Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea,Department of Radiology, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jeong Min Lee
- Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea,Department of Radiology, Seoul National University College of Medicine, Seoul, Republic of Korea,Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul, Republic of Korea,*Jeong Min Lee, MD, Ph.D, Department of Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 110-744 (Republic of Korea), Tel. +82 2 2072 3154, E-Mail
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Simo KA, Halpin LE, McBrier NM, Hessey JA, Baker E, Ross S, Swan RZ, Iannitti DA, Martinie JB. Multimodality treatment of intrahepatic cholangiocarcinoma: A review. J Surg Oncol 2016; 113:62-83. [DOI: 10.1002/jso.24093] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2015] [Accepted: 10/31/2015] [Indexed: 02/06/2023]
Affiliation(s)
- Kerri A. Simo
- Hepatobiliary and Pancreas Surgery; ProMedica Health System; Toledo Ohio
- ProMedica Cancer Institute; ProMedica Health System; Toledo Ohio
- Department of Surgery; University of Toledo Medical College; Toledo Ohio
| | - Laura E. Halpin
- Department of Surgery; University of Toledo Medical College; Toledo Ohio
| | - Nicole M. McBrier
- Hepatobiliary and Pancreas Surgery; ProMedica Health System; Toledo Ohio
- ProMedica Cancer Institute; ProMedica Health System; Toledo Ohio
| | | | - Erin Baker
- Hepatobiliary and Pancreas Surgery; Carolinas Medical Center; Charlotte North Carolina
| | - Samuel Ross
- Hepatobiliary and Pancreas Surgery; Carolinas Medical Center; Charlotte North Carolina
| | - Ryan Z. Swan
- Hepatobiliary and Pancreas Surgery; Carolinas Medical Center; Charlotte North Carolina
| | - David A. Iannitti
- Hepatobiliary and Pancreas Surgery; Carolinas Medical Center; Charlotte North Carolina
| | - John B. Martinie
- Hepatobiliary and Pancreas Surgery; Carolinas Medical Center; Charlotte North Carolina
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Song PP, Xia JF, Inagaki Y, Hasegawa K, Sakamoto Y, Kokudo N, Tang W. Controversies regarding and perspectives on clinical utility of biomarkers in hepatocellular carcinoma. World J Gastroenterol 2016; 22:262-274. [PMID: 26755875 PMCID: PMC4698491 DOI: 10.3748/wjg.v22.i1.262] [Citation(s) in RCA: 83] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2015] [Revised: 07/27/2015] [Accepted: 10/13/2015] [Indexed: 02/06/2023] Open
Abstract
The prevalence of hepatocellular carcinoma (HCC) worldwide parallels that of persistent infection with the hepatitis B virus (HBV) and/or hepatitis C virus (HCV). According to recommendations by the World Health Organization guidelines for HBV/HCV, alpha-fetoprotein (AFP) testing and abdominal ultrasound should be performed in routine surveillance of HCC every 6 mo for high-risk patients. These examinations have also been recommended worldwide by many other HCC guidelines over the past few decades. In recent years, however, the role of AFP in HCC surveillance and diagnosis has diminished due to advances in imaging modalities. AFP was excluded from the surveillance and/or diagnostic criteria in the HCC guidelines published by the American Association for the Study of Liver Diseases in 2010, the European Association for the Study of the Liver in 2012, and the National Comprehensive Cancer Network in 2014. Other biomarkers, including the Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), des-γ-carboxyprothrombin, Dickkopf-1, midkine, and microRNA, are being studied in this regard. Furthermore, increasing attention has focused on the clinical utility of biomarkers as pre-treatment predictors for tumor recurrence and as post-treatment monitors. Serum and tissue-based biomarkers and genomics may aid in the diagnosis of HCC, determination of patient prognosis, and selection of appropriate treatment. However, further studies are needed to better characterize the accuracy and potential role of these approaches in clinical practice.
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Yang CC, Yang H, Guo MJ, Li WH, Wu YF. Contrast-enhanced CT imaging in distinguishing intrahepatic cholangiocarcinoma from poorly differentiated hepatocellular carcinoma. Shijie Huaren Xiaohua Zazhi 2015; 23:4725-4732. [DOI: 10.11569/wcjd.v23.i29.4725] [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] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the contrast-enhanced computed tomography (CT) features in differentiating intrahepatic cholangiocarcinoma (ICC) from poorly differentiated hepatocellular carcinoma (p-HCC).
METHODS: Sixty-eight patients with pathologically confirmed ICC (n = 28) or p-HCC (n = 40) were enrolled. The clinical and imaging features were investigated retrospectively.
RESULTS: Univariate analysis showed that lobulated shape (P = 0.010), bile duct dilation (P = 0.031), intratumoral artery (P = 0.020), rim enhancement (P = 0.002), delayed enhancement (P = 0.021) and quick washout (P < 0.001) were associated with the differences between ICC and p-HCC. Multivariate logistic regression analysis revealed that intratumoral artery was a significant, independent predictive factor of ICC (P = 0.026), with 13 (46.43%) ICCs showing this feature. Quick washout significantly favored p-HCC (P = 0.015), and 25 p-HCCs (62.5%) showed this feature.
CONCLUSION: The presence of an intratumoral artery in the arterial phase on contrast-enhanced dynamic CT is an important factor for predicting ICC, while a quick washout is a predictable finding for p-HCC. Accurate imaging diagnosis between ICC and p-HCC can provide an objective basis for making reasonable, timely treatment.
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Wengert GJ, Bickel H, Breitenseher J, Ba-Ssalamah A. [Primary liver tumors : hepatocellular versus intrahepatic cholangiocellular carcinoma]. Radiologe 2015; 55:27-35. [PMID: 25575724 DOI: 10.1007/s00117-014-2705-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
CLINICAL ISSUE Hepatocellular carcinoma (HCC) and intrahepatic cholangiocellular carcinoma (ICC) are the most commonly occurring and important primary liver tumors. Originating from one pluripotent liver stem cell both tumor entities can occur in a cirrhotic liver and also in patients without cirrhosis. Several risk factors have been identified as causative for both carcinomas; therefore, tumor screening is advantageous, especially for high-risk patients who could be diagnosed in an early stage to allow curative treatment. Surgical resection, interventional procedures and transplantation are available as curative treatment options when diagnosed in time. STANDARD RADIOLOGICAL METHODS Common characteristic features and morphology in cross-sectional imaging by ultrasound (US), multidetector computed tomography (CT) and magnetic resonance imaging (MRI) as well as screening aspects are presented and discussed. METHODICAL INNOVATIONS Recent findings show a better understanding of the carcinogenesis model of both liver tumors originating from one pluripotent liver stem cell. Further developments of modern cross-sectional imaging modalities, especially MRI in combination with diffusion-weighted imaging and intravenous administration of hepatocyte-specific contrast agents enable early detection, exact differentiation, staging and treatment evaluation of HCC and ICC ACHIEVEMENTS: In this article we discuss modern, multiparametric imaging modalities, which allow a complete and reliable diagnosis of the majority of these tumor entities. PRACTICAL RECOMMENDATIONS Contrast-enhanced MRI, using hepatocyte-specific contrast agents, is currently the most accurate procedure for the noninvasive diagnosis and treatment evaluation of HCC and ICC.
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Affiliation(s)
- G J Wengert
- Universitätsklinik für Radiologie und Nuklearmedizin, Allgemeines Krankenhaus, Medizinische Universität Wien, Währinger-Gürtel 18-20, 1090, Wien, Österreich,
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Suzuki H, Komuta M, Bolog A, Yokobori T, Wada S, Araki K, Kubo N, Watanabe A, Tsukagoshi M, Kuwano H. Relationship between 18-F-fluoro-deoxy-D-glucose uptake and expression of glucose transporter 1 and pyruvate kinase M2 in intrahepatic cholangiocarcinoma. Dig Liver Dis 2015; 47:590-6. [PMID: 25912843 DOI: 10.1016/j.dld.2015.03.017] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2014] [Revised: 03/08/2015] [Accepted: 03/17/2015] [Indexed: 12/11/2022]
Abstract
BACKGROUND Cholangiocellular carcinoma is characterized by elevated glucose consumption, resulting in an increased uptake of 18F-2-fluoro-2-deoxy-d-glucose (18F-FDG). This study investigates the relationship between 18F-FDG uptake and tumour glucose metabolism. METHODS This was a retrospective analysis of 19 patients with cholangiocellular carcinoma. Immunohistochemistry for glucose transporter 1 and pyruvate kinase type M2 were performed. Overall tumour glucose metabolism was evaluated by measuring 18F-FDG uptake and the protein expression levels of glucose transporter 1 and pyruvate kinase type M2. RESULTS 18F-FDG uptake had a strong positive correlation with histological differentiation. Both tumour status (p=0.044) and tumour size (p=0.011) were correlated with primary tumour 18F-FDG uptake. Glucose transporter 1 expression correlated with histological differentiation (p=0.017), while pyruvate kinase type M2 expression tended to correlate with lymph node metastasis (p=0.051). Glucose transporter 1 expression was strongly related to the standard uptake value (p=0.001), but that of pyruvate kinase type M2 was not (p=0.461). CONCLUSIONS Glucose transporter 1 expression exhibits a strong correlation with 18F-FDG uptake in cholangiocellular carcinoma tissue, while pyruvate kinase type M2 expression was not associated with fluoro-2-deoxy-d-glucose uptake. In addition to its glycolytic function, pyruvate kinase type M2 has a variety of roles and its expression may enhance tumour cell invasion and promote the lymph node metastasis of intrahepatic cholangiocarcinoma.
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Affiliation(s)
- Hideki Suzuki
- Department of General Surgical Science (Surgery I), Graduate School of Medicine, Gunma University, Japan.
| | - Mina Komuta
- Pathology Service, Saint-Luc University, Belgium
| | - Altan Bolog
- Department of General Surgical Science (Surgery I), Graduate School of Medicine, Gunma University, Japan
| | - Takehiko Yokobori
- Department of General Surgical Science (Surgery I), Graduate School of Medicine, Gunma University, Japan
| | - Satoshi Wada
- Department of General Surgical Science (Surgery I), Graduate School of Medicine, Gunma University, Japan
| | - Kenichiro Araki
- Department of General Surgical Science (Surgery I), Graduate School of Medicine, Gunma University, Japan
| | - Norio Kubo
- Department of General Surgical Science (Surgery I), Graduate School of Medicine, Gunma University, Japan
| | - Akira Watanabe
- Department of General Surgical Science (Surgery I), Graduate School of Medicine, Gunma University, Japan
| | - Mariko Tsukagoshi
- Department of General Surgical Science (Surgery I), Graduate School of Medicine, Gunma University, Japan
| | - Hiroyuki Kuwano
- Department of General Surgical Science (Surgery I), Graduate School of Medicine, Gunma University, Japan
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Lin MT, Chang KC, Chou YP, Tseng PL, Yen YH, Wang CC, Tsai MC, Cheng YF, Eng HL, Wu CK, Hu TH. The validation of the 2010 American Association for the Study of Liver Diseases guideline for the diagnosis of hepatocellular carcinoma in an endemic area. J Gastroenterol Hepatol 2015; 30:345-51. [PMID: 25092265 DOI: 10.1111/jgh.12699] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/28/2014] [Indexed: 01/10/2023]
Abstract
BACKGROUND AND AIM Hepatocellular carcinoma (HCC) diagnosis could be made with one typical imaging study in a cirrhotic liver by the guideline of the American Association for the Study of Liver Diseases (AASLD) in 2010. Patients with hepatitis B who may not have fully developed cirrhosis could be applied. We aim to retrospectively analyze and validate the diagnostic power of the 2010 guideline in an HCC endemic area (Taiwan). METHODS From January 2006 to December 2010, a total of 648 patients with liver tumor post-surgical resection were reviewed. The fibrotic scores were verified by METAVIR score 4. Among the 648 patients, 569 (87.8%) were HCC patients. Hepatitis B accounts for 54.5%, hepatitis C 21.9%, hepatitis B + C 2.8%, and non-hepatitis B or C 20.7% of patients. Two hundred eighty-eight of 648 (44%) patients were with cirrhotic liver. RESULTS The diagnostic sensitivity, specificity, positive predictive value (PPV), negative predictive value, and accuracy of the 2010 AASLD guideline f are 99.1%, 36.7%, 91.9%, 85.3%, and 91.5%, respectively. Cirrhotic liver exhibited a higher PPV (P < 0.001) but lower specificity (P = 0.0479) than non-cirrhotic liver. In both cirrhotic and non-cirrhotic condition, no difference existed in patients with hepatitis B or hepatitis C (P > 0.05). CONCLUSIONS Similar sensitivity of HCC diagnosis existed between cirrhotic and non-cirrhotic liver, and across different fibrotic stages. But cirrhotic liver exhibited a higher PPV. Hepatitis B or C has no decisive effect in HCC diagnosis.
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Affiliation(s)
- Ming-Tsung Lin
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
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Wu ZF, Wu XY, Zhu N, Xu Z, Li WS, Zhang HB, Yang N, Yao XQ, Liu FK, Yang GS. Prognosis after resection for hepatitis B virus-associated intrahepatic cholangiocarcinoma. World J Gastroenterol 2015; 21:935-943. [PMID: 25624728 PMCID: PMC4299347 DOI: 10.3748/wjg.v21.i3.935] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2014] [Revised: 07/12/2014] [Accepted: 09/19/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the prognostic factors after resection for hepatitis B virus (HBV)-associated intrahepatic cholangiocarcinoma (ICC) and to assess the impact of different extents of lymphadenectomy on patient survival.
METHODS: A total of 85 patients with HBV-associated ICC who underwent curative resection from January 2005 to December 2006 were analyzed. The patients were classified into groups according to the extent of lymphadenectomy (no lymph node dissection, sampling lymph node dissection and regional lymph node dissection). Clinicopathological characteristics and survival were reviewed retrospectively.
RESULTS: The cumulative 1-, 3-, and 5-year survival rates were found to be 60%, 18%, and 13%, respectively. Multivariate analysis revealed that liver cirrhosis (HR = 1.875, 95%CI: 1.197-3.278, P = 0.008) and multiple tumors (HR = 2.653, 95%CI: 1.562-4.508, P < 0.001) were independent prognostic factors for survival. Recurrence occurred in 70 patients. The 1-, 3-, and 5-year disease-free survival rates were 36%, 3% and 0%, respectively. Liver cirrhosis (HR = 1.919, P = 0.012), advanced TNM stage (stage III/IV) (HR = 2.027, P < 0.001), and vascular invasion (HR = 3.779, P = 0.02) were independent prognostic factors for disease-free survival. Patients with regional lymph node dissection demonstrated a similar survival rate to patients with sampling lymph node dissection. Lymphadenectomy did not significantly improve the survival rate of patients with negative lymph node status.
CONCLUSION: The extent of lymphadenectomy does not seem to have influence on the survival of patients with HBV-associated ICC, and routine lymph node dissection is not recommended, particularly for those without lymph node metastasis.
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Amini N, Ejaz A, Spolverato G, Maithel SK, Kim Y, Pawlik TM. Management of lymph nodes during resection of hepatocellular carcinoma and intrahepatic cholangiocarcinoma: a systematic review. J Gastrointest Surg 2014; 18:2136-48. [PMID: 25300798 DOI: 10.1007/s11605-014-2667-1] [Citation(s) in RCA: 84] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2014] [Accepted: 09/22/2014] [Indexed: 01/31/2023]
Abstract
The role of lymph node dissection (LND) in the treatment of patients with hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICC) remains controversial. We sought to systematically review all available evidence to determine the role of LND in patients with HCC and ICC. Studies that reported on LND, lymph node metastasis (LNM), and short- and long-term outcomes for patients with HCC or ICC survival were identified from PubMed, Cochrane, Embase, Scopus, and Web of Science databases. Data were extracted, synthesized, and analyzed using standard techniques. A total of 603 and 434 references were identified for HCC and ICC, respectively. Among HCC patients, the overall prevalence of LND was 51.6 % (95 % confidence interval (CI) 19.7-83.5) with an associated LNM incidence of 44.5 % (95 % CI 27.4-61.7). LNM was associated with a 3- and 5-year survival of 27.5 and 20.8 %, respectively. Among ICC patients, most patients 78.5 % (95 % CI 76.2-80.7) underwent LND; 45.2 % (95 % CI 39.2-51.2) had LNM. Three and 5-year survival among ICC patients with LNM was 0.2 % (95 % CI 0-0.7) and 0 %, respectively. While there are insufficient data to recommend a routine LND in all patients with HCC or ICC, the potential prognostic value of LND suggests that LND should at least be considered at the time of surgery.
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Affiliation(s)
- Neda Amini
- Department of Surgery, Johns Hopkins Hospital, 600 N. Wolfe Street, Blalock 688, Baltimore, MD, 21287, USA
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Atanasov G, Schmelzle M, Thelen A, Wiltberger G, Hau HM, Krenzien F, Petersen TO, Moche M, Jonas S. Selective hypertrophy of the lobus caudatus as a novel approach enabling extended right hepatectomy in the presence of a non-perfused left lateral liver lobe. Clin J Gastroenterol 2014; 7:370-5. [PMID: 25285175 PMCID: PMC4176950 DOI: 10.1007/s12328-014-0511-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2013] [Accepted: 06/23/2014] [Indexed: 11/29/2022]
Abstract
Introduction Portal vein embolization (PVE) is a well-established technique to enhance functional hepatic reserves of segments II and III before curative extended right hepatectomy for tumors of the right liver lobe. However, an adequate hepatopetal flow of the left lateral portal vein branches is required for a sufficient PVE-associated hypertrophy. Case report Here, we report a 65-year old patient suffering from a locally advanced intrahepatic cholangiocarcinoma in the right liver lobe and segment IV. A curative extended right hepatectomy after preoperative PVE of liver segments IV–VIII was initially impossible because of partial thrombosis of the left lateral portal vein branches resulting in an ischemic-type atrophy of segments II and III. However, due to a massive hypertrophy of the caudate lobe following PVE of liver segments IV–VIII, subsequent extended right hepatectomy with intraoperative thrombectomy of segments II and III was made possible. Conclusions To our knowledge this is the first case in which an extended right hepatectomy for a liver malignancy, in the presence of atrophic left lateral section, was made possible by a massive PVE-associated hypertrophy of the caudate lobe.
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Affiliation(s)
- Georgi Atanasov
- Department of Visceral-, Transplantation-, Thoracic- and Vascular Surgery, University Hospital Leipzig, Liebigstrasse 20, 04103 Leipzig, Germany
| | - Moritz Schmelzle
- Department of Visceral-, Transplantation-, Thoracic- and Vascular Surgery, University Hospital Leipzig, Liebigstrasse 20, 04103 Leipzig, Germany ; Translational Centre for Regenerative Medicine, Leipzig University, Leipzig, Germany
| | - Armin Thelen
- Department of Visceral-, Transplantation-, Thoracic- and Vascular Surgery, University Hospital Leipzig, Liebigstrasse 20, 04103 Leipzig, Germany
| | - Georg Wiltberger
- Department of Visceral-, Transplantation-, Thoracic- and Vascular Surgery, University Hospital Leipzig, Liebigstrasse 20, 04103 Leipzig, Germany
| | - Hans-Michael Hau
- Department of Visceral-, Transplantation-, Thoracic- and Vascular Surgery, University Hospital Leipzig, Liebigstrasse 20, 04103 Leipzig, Germany
| | - Felix Krenzien
- Department of Visceral-, Transplantation-, Thoracic- and Vascular Surgery, University Hospital Leipzig, Liebigstrasse 20, 04103 Leipzig, Germany
| | - Tim-Ole Petersen
- Department of Diagnostic and Interventional Radiology, University Hospital Leipzig, Leipzig, Germany
| | - Michael Moche
- Department of Diagnostic and Interventional Radiology, University Hospital Leipzig, Leipzig, Germany
| | - Sven Jonas
- Department of Visceral-, Transplantation-, Thoracic- and Vascular Surgery, University Hospital Leipzig, Liebigstrasse 20, 04103 Leipzig, Germany ; Translational Centre for Regenerative Medicine, Leipzig University, Leipzig, Germany
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