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Zhang L, Zhuge Y, Ni J. BUB1 serves as a biomarker for poor prognosis in liver hepatocellular carcinoma. BMC Immunol 2025; 26:20. [PMID: 40069598 PMCID: PMC11895216 DOI: 10.1186/s12865-025-00698-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2024] [Accepted: 02/27/2025] [Indexed: 03/15/2025] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is the most frequent kind of liver cancer with high morbidity and mortality rates worldwide. Altered expression of BUB1 (budding uninhibited by benzimidazole 1) gene leads to chromosome instability and aneuploidy. This study investigated the expression of BUB1 and its prognostic value as well as its correlation with immune cell infiltration and immune checkpoints in HCC. RESULTS Using the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases, we found that BUB1 was up-regulated in HCC, thus prompting us to validate this observation by immunohistochemistry on 57 HCC paraffin embedded tissues from Wuxi No.2 People's Hospital. Kaplan-Meier survival analysis revealed that HCC patients with high BUB1 expression had shorter overall survival (OS) time as well as progression-free interval (PFI), and disease-specific survival (DSS) time compared to the patients with low BUB1 expression. Besides, STRING database showed that the top 10 co-expression genes were mainly involved in the regulation of cell division during the mitosis. Gene Ontology (GO) analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that BUB1 had a connection to cancer related pathways. Lastly, The Tumor Immune Estimation Resource (TIMER) analysis found that BUB1 was positively related to immune cell infiltration and some immune checkpoint gene in HCC. CLINICAL TRIAL NUMBER Not applicable. CONCLUSIONS Our present study demonstrated that BUB1 is a potential prognostic biomarker, and BUB1 may play a role in the tumor immune microenvironment in HCC.
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Affiliation(s)
- Lili Zhang
- Department of Gastroenterology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu Province, China.
- Department of Gastroenterology, Jiangnan University Medical Center, Wuxi No.2 People's Hospital, Wuxi, Jiangsu Province, China.
| | - Yuzheng Zhuge
- Department of Gastroenterology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu Province, China.
| | - Jingbin Ni
- Department of Gastroenterology, Jiangnan University Medical Center, Wuxi No.2 People's Hospital, Wuxi, Jiangsu Province, China
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Yang S, Ni H, Zhang A, Zhang J, Zang H, Ming Z. Significance of anatomical resection and wide surgical margin for HCC patients with MVI undergoing laparoscopic hepatectomy: A multicenter study. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2025; 51:109353. [PMID: 39489041 DOI: 10.1016/j.ejso.2024.109353] [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: 09/17/2024] [Revised: 10/24/2024] [Accepted: 10/29/2024] [Indexed: 11/05/2024]
Abstract
OBJECTIVE To investigate the impact of surgical resection margin and hepatic resection type on prognosis and compare their prognostic significance on patients with hepatocellular carcinoma (HCC) with or without microvascular invasion (MVI) who underwent laparoscopic liver resection (LLR). METHODS A retrospective analysis was conducted on 320 patients with HCC who underwent LLR. According to the grading of MVI, patients were classified as M0, M1 and M2. Patients were divided into the anatomical resection (AR) and nonanatomical resection (NAR) groups according to the hepatic resection type. Survival and Cox regression analyses were performed to explore the effects of AR and NAR, wide and narrow resection margin on overall survival (OS) and time to recurrence (TTR). RESULTS In the whole cohort, narrow resection margin was an independent risk factor for OS and TTR, whereas NAR was not. Subgroup analysis showed that narrow resection margin and NAR were both independent risk factors for OS and TTR in HCC patients with MVI. The 5-year OS and TTR rates of the two groups (NAR-wide resection margin and AR-narrow resection margin) with M1 were 85.3 % versus 62 % and 34.4 % versus 60.2 %. Similarly, the 5-year OS and TTR rates of the two groups (NAR-wide resection margin and AR-narrow resection margin) with M2 were 80.2 % versus 47.9 % and 30.8 % versus 64.8 %. CONCLUSIONS Anatomical hepatectomy and wide resection margin were independent protective factors for HCC patients with MVI receiving LLR. Nonetheless, wide resection margin had a greater impact on prognosis than anatomical hepatectomy.
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Affiliation(s)
- Shiye Yang
- Department of Comprehensive Surgery, Vascular Surgery, Nantong First People's Hospital, Affiliated Hospital 2 of Nantong University, 666 Shengli Road, Chongchuan District, Nantong City, Jiangsu Province, 226014, China
| | - Haishun Ni
- Department of General Surgery, Nantong Second People's Hospital, 298 Xinhua Road, Gangzha District, Nantong City, Jiangsu Province, 226002, China
| | - Aixian Zhang
- Department of Hepato-Biliary-Pancreatic Surgery, Chinese People's Liberation Army (PLA) General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100080, China
| | - Jixiang Zhang
- Department of Hepatobiliary Surgery, Zhongshan People's Hospital, 2 Sun Wen East Road, Zhongshan City, Guangdong Province, 528403, China
| | - Hong Zang
- Department of Comprehensive Surgery, Hepato-Biliary-Pancreatic Surgery, Nantong First People's Hospital, Affiliated Hospital 2 of Nantong University, 666 Shengli Road, Chongchuan District, Nantong City, Jiangsu Province, 226014, China.
| | - Zhibing Ming
- Department of Comprehensive Surgery, Vascular Surgery, Nantong First People's Hospital, Affiliated Hospital 2 of Nantong University, 666 Shengli Road, Chongchuan District, Nantong City, Jiangsu Province, 226014, China.
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Hu R, Xu J, Wang H, Wang J, Lei K, Zhao X, Zhang H, You K, Liu Z. Impact of preoperative transcatheter arterial chemoembolization (TACE) on postoperative long-term survival in patients with nonsmall hepatocellular carcinoma: a propensity score matching analysis. BMC Cancer 2024; 24:190. [PMID: 38336712 PMCID: PMC10858462 DOI: 10.1186/s12885-024-11978-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Accepted: 02/07/2024] [Indexed: 02/12/2024] Open
Abstract
BACKGROUND The purpose of this propensity score matching (PSM) analysis was to compare the effects of preoperative transcatheter arterial chemoembolization (TACE) and non-TACE on the long-term survival of patients who undergo radical hepatectomy. METHODS PSM analysis was performed for 387 patients with hepatocellular carcinoma (HCC) (single > 3 cm or multiple) who underwent radical resection of HCC at our centre from January 2011 to June 2018. The patients were allocated to a preoperative TACE group (n = 77) and a non-TACE group (n = 310). The main outcome measures were progression-free survival (PFS) and overall survival (OS) since the treatment date. RESULTS After PSM, 67 patients were included in each of the TACE and non-TACE groups. The median PFS times in the preoperative TACE and non-TACE groups were 24.0 and 11.3 months, respectively (p = 0.0117). The median OS times in the preoperative TACE and non-TACE groups were 41.5 and 29.0 months, respectively (p = 0.0114). Multivariate Cox proportional hazard regression analysis revealed that preoperative TACE (hazard ratio, 1.733; 95% CI, 1.168-2.570) and tumour thrombosis (hazard ratio, 0.323; 95% CI, 0.141-0.742) were independent risk factors significantly associated with OS. CONCLUSIONS Preoperative TACE is related to improving PFS and OS after resection of HCC. Preoperative TACE and tumour thrombus volume were also found to be independent risk factors associated with OS.
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Affiliation(s)
- Run Hu
- The Second Affiliated Hospital of Chongqing Medical University, 74# Linjiang Road, Yuzhong District, Chongqing, 400000, China
| | - Jie Xu
- The Second Affiliated Hospital of Chongqing Medical University, 74# Linjiang Road, Yuzhong District, Chongqing, 400000, China
| | - Hongxiang Wang
- The Second Affiliated Hospital of Chongqing Medical University, 74# Linjiang Road, Yuzhong District, Chongqing, 400000, China
| | - Jiaguo Wang
- The Second Affiliated Hospital of Chongqing Medical University, 74# Linjiang Road, Yuzhong District, Chongqing, 400000, China
| | - Kai Lei
- The Second Affiliated Hospital of Chongqing Medical University, 74# Linjiang Road, Yuzhong District, Chongqing, 400000, China
| | - Xiaoping Zhao
- The Second Affiliated Hospital of Chongqing Medical University, 74# Linjiang Road, Yuzhong District, Chongqing, 400000, China
| | - Huizhi Zhang
- The Second Affiliated Hospital of Chongqing Medical University, 74# Linjiang Road, Yuzhong District, Chongqing, 400000, China
| | - Ke You
- The Second Affiliated Hospital of Chongqing Medical University, 74# Linjiang Road, Yuzhong District, Chongqing, 400000, China
| | - Zuojin Liu
- The Second Affiliated Hospital of Chongqing Medical University, 74# Linjiang Road, Yuzhong District, Chongqing, 400000, China.
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Wicks JS, Dale BS, Ruffolo L, Pack LJ, Dunne R, Laryea MA, Hernandez-Alejandro R, Sharma AK. Comparable and Complimentary Modalities for Treatment of Small-Sized HCC: Surgical Resection, Radiofrequency Ablation, and Microwave Ablation. J Clin Med 2023; 12:5006. [PMID: 37568408 PMCID: PMC10419984 DOI: 10.3390/jcm12155006] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Revised: 07/20/2023] [Accepted: 07/28/2023] [Indexed: 08/13/2023] Open
Abstract
BACKGROUND Over the past decade, there has been continual improvement in both ablative and surgical technologies for the treatment of hepatocellular carcinoma (HCC). The efficacy of ablative therapy compared to surgical resection for HCC has not been thoroughly evaluated using multiple large-scale randomized controlled trials. By international consensus, if a patient is eligible, surgery is the primary curative treatment option, as it is believed to confer superior oncologic control. OBJECTIVE to determine the efficacies of percutaneous ablative therapies and surgical resection (SR) in the treatment of HCC. Data sources, study appraisal, and synthesis methods: A meta-analysis using 5 online databases dating back to 1989 with more than 31,000 patients analyzing patient and tumor characteristics, median follow-up, overall survival, and complication rate was performed. RESULTS Ablative therapies are suitable alternatives to surgical resection in terms of survival and complication rates for comparable patient populations. For the entire length of the study from 1989-2019, radiofrequency ablation (RFA) produced the highest 5-year survival rates (59.6%), followed by microwave ablation (MWA) (50.7%) and surgical resection (SR) (49.9%). In the most recent era from 2006 to 2019, surgical resection has produced the highest 5-year survival rate of 72.8%, followed by RFA at 61.7% and MWA at 50.6%. Conclusions and key findings: Depending on the disease state and comorbidities of the patient, one modality may offer superior overall survival rates over the other available techniques. Interventional ablative methods and surgical resection should be used in conjunction for the successful treatment of small-sized HCC.
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Affiliation(s)
- Jeffrey S. Wicks
- Department of Biology, University of Rochester, Rochester, NY 14642, USA;
| | - Benjamin S. Dale
- Department of Surgery, University of Rochester, Rochester, NY 14642, USA; (B.S.D.); (L.R.)
| | - Luis Ruffolo
- Department of Surgery, University of Rochester, Rochester, NY 14642, USA; (B.S.D.); (L.R.)
| | - Ludia J. Pack
- Department of Genetics, University of Rochester, Rochester, NY 14642, USA;
| | - Richard Dunne
- Division of Hematology/Oncology, Department of Medicine, University of Rochester, Rochester, NY 14642, USA;
| | - Marie A. Laryea
- Division of Gastroenterology/Hepatology, Department of Medicine, University of Rochester, Rochester, NY 14642, USA;
| | | | - Ashwani Kumar Sharma
- Division of Interventional Radiology, Department of Imaging Sciences, University of Rochester, Rochester, NY 14642, USA
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SOS1 regulates HCC cell epithelial-mesenchymal transition via the PI3K/AKT/mTOR pathway. Biochem Biophys Res Commun 2022; 637:161-169. [DOI: 10.1016/j.bbrc.2022.11.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Revised: 11/07/2022] [Accepted: 11/08/2022] [Indexed: 11/13/2022]
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Limitations of Nerve Fiber Density as a Prognostic Marker in Predicting Oncological Outcomes in Hepatocellular Carcinoma. Cancers (Basel) 2022; 14:cancers14092237. [PMID: 35565366 PMCID: PMC9103173 DOI: 10.3390/cancers14092237] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Revised: 04/21/2022] [Accepted: 04/25/2022] [Indexed: 02/07/2023] Open
Abstract
It has been shown that the presence and density of nerve fibers (NFs; NFD) in the tumor microenvironment (TME) may play an important prognostic role in predicting long-term oncological outcomes in various malignancies. However, the role of NFD in the prognosis of hepatocellular carcinoma (HCC) is yet to be explored. To this end, we aimed to investigate the impact of NFs on oncological outcomes in a large European single-center cohort of HCC patients. In total, 153 HCC patients who underwent partial hepatectomy in a curative-intent setting between 2010 and 2021 at our university hospital were included in this study. Group comparisons between patients with and without NFs were conducted and the association of recurrence-free survival (RFS) and overall survival (OS) with the presence of NFs and other clinico-pathological variables were determined by univariate and multivariable Cox regression models. Patients with NFs in the TME presented with a median OS of 66 months (95% CI: 30−102) compared to 42 months (95% CI: 20−63) for patients without NFs (p = 0.804 log-rank). Further, RFS was 26 months (95% CI: 12−40) for patients with NFs compared to 18 months (95% CI: 9−27) for patients without NFs (p = 0.666 log-rank). In a subgroup analysis, patients with NFD ≤ 5 showed a median OS of 54 months (95% CI: 11−97) compared to 48 months (95% CI: 0−106) for the group of patients with NFD > 5 (p = 0.787 log-rank). Correspondingly, the RFS was 26 months (95% CI: 10−42) in patients with NFD ≤ 5 and 29 months (95% CI: 14−44) for the subcohort with NFD > 5 (p = 0.421 log-rank). Further, group comparisons showed no clinico-pathological differences between patients with NFs (n = 76) and without NFs (n = 77) and NFs were not associated with OS (p = 0.806) and RFS (p = 0.322) in our Cox regression models. In contrast to observations in various malignancies, NFs in the TME and NFD are not associated with long-term oncological outcomes in HCC patients undergoing surgery.
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Ezzat R, Eltabbakh M, El Kassas M. Unique situation of hepatocellular carcinoma in Egypt: A review of epidemiology and control measures. World J Gastrointest Oncol 2021; 13:1919-1938. [PMID: 35070033 PMCID: PMC8713321 DOI: 10.4251/wjgo.v13.i12.1919] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Revised: 04/17/2021] [Accepted: 10/18/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the sixth most common primary malignancy worldwide, and the third most common cause of death among cancers worldwide. HCC occurs in several pre-existing conditions, including hepatitis C, hepatitis B virus, and non-alcoholic cirrhosis. Egypt used to be the country with the heaviest hepatitis C virus (HCV) burden. The relationship between HCV and HCC is an important research area. In Egypt, HCC is a significant public health problem. A possible cause for the increasing rates of detection of HCC in Egypt is the mass screening program that was carried by the government for detecting and treating HCV. A multidisciplinary approach is now widely applied to HCC management in health centers all over Egypt. Different treatment modalities are available in Egypt, with success rates comparable to global rates. The Egyptian health authorities have made the elimination of HCV from Egypt a special priority, and this approach should lead to a decrease in number of HCC cases in the near future. In this article we review the current situation of HCC in Egypt, including epidemiological aspects, relevant risk factors for HCC development, strategies, and efforts established by health authorities for the screening and prevention of both HCV and HCC in Egypt. We highlight the different modalities for HCC treatment.
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Affiliation(s)
- Reem Ezzat
- Internal Medicine Department, Faculty of Medicine, Assiut University, Assiut 71515, Egypt
| | - Mohamed Eltabbakh
- Tropical Medicine Department, Faculty of Medicine, Ain Shams University, Cairo 11566, Egypt
| | - Mohamed El Kassas
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo 11795, Cairo, Egypt
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Construction and Comprehensive Analyses of a Competing Endogenous RNA Network in Tumor-Node-Metastasis Stage I Hepatocellular Carcinoma. BIOMED RESEARCH INTERNATIONAL 2020; 2020:5831064. [PMID: 32104698 PMCID: PMC7036093 DOI: 10.1155/2020/5831064] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/26/2019] [Revised: 12/14/2019] [Accepted: 12/26/2019] [Indexed: 12/14/2022]
Abstract
Background Long noncoding RNAs (lncRNAs) can function as competing endogenous RNAs (ceRNAs) and interact with microRNAs (miRNAs) to regulate target gene expression, which can greatly influence tumor development and progression. Different tumor-node-metastasis (TNM) stages of hepatocellular carcinoma (HCC) defined by the American Joint Committee on Cancer (AJCC) have different clinical results. Our purpose was to comprehensively analyze differentially expressed (DE) lncRNAs, miRNAs, and mRNAs in stage I HCC and identify prognosis-associated RNAs. Methods RNA-seq data were obtained from The Cancer Genome Atlas (TCGA) database. A stage I HCC-associated miRNA-lncRNA-mRNA network was constructed. Next, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway analyses of ceRNA-associated DEmRNAs were performed using Database for Annotation, Visualization, and Integrated Discovery (DAVID) 6.8 and Clusterprofile in the R package. The protein-protein interaction (PPI) network of the above mRNAs was then constructed using STRING. Finally, the association between lncRNAs and mRNAs in the ceRNA network and prognosis of patients was further analyzed. Linear regression analysis of the above lncRNAs and mRNAs associated with overall survival was performed. Results After a comparison between HCC and adjacent nontumor tissues, 778 lncRNAs, 1608 mRNAs, and 102 miRNAs that were abnormally expressed were identified. The ceRNA network was composed of 56 DElncRNAs, 14 DEmiRNAs, and 30 DEmRNAs. Functional analysis results showed that 30 DEmRNAs were enriched in 14 GO biological process categories and 6 KEGG categories (false discovery rate (FDR) < 0.05). A PPI network was composed of 22 nodes and 58 edges. We detected 4 DElncRNAs (BPESC1, AC061975.6, AC079341.1, and CLLU1) and 6 DEmRNAs (CEP55, E2F1, E2F7, EZH2, G6PD, and SLC7A11) that had significant influences on the overall survival (OS) of stage I HCC patients (P < 0.05). lncRNA BPESC1 was positively correlated with mRNA CEP55 via miR-424, and lncRNA AC061975.6 was positively correlated with mRNA E2F1 via miR-519d. Conclusion Our study identified novel lncRNAs and mRNAs that were associated with the progression and prognosis of stage I HCC and further investigated the regulatory mechanism of lncRNA-mediated ceRNAs in the development of stage I HCC.
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Tsunedomi R, Yoshimura K, Suzuki N, Hazama S, Nagano H. Clinical implications of cancer stem cells in digestive cancers: acquisition of stemness and prognostic impact. Surg Today 2020; 50:1560-1577. [PMID: 32025858 DOI: 10.1007/s00595-020-01968-x] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2019] [Accepted: 01/14/2020] [Indexed: 02/06/2023]
Abstract
Digestive system cancers are the most frequent cancers worldwide and often associated with poor prognosis because of their invasive and metastatic characteristics. Recent studies have found that the plasticity of cancer cells can impart cancer stem-like properties via the epithelial-mesenchymal transition (EMT). Cancer stem-like properties such as tumor initiation are integral to the formation of metastasis, which is the main cause of poor prognosis. Numerous markers of cancer stem cells (CSCs) have been identified in many types of cancer. Therefore, CSCs, via their stem cell-like functions, may play an important role in prognosis after surgery. While several reports have described prognostic analysis using CSC markers, few reviews have summarized CSCs and their association with prognosis. Herein, we review the prognostic potential of eight CSC markers, CD133, CD44, CD90, ALDH1A1, EPCAM, SOX2, SOX9, and LGR5, in digestive cancers including those of the pancreas, colon, liver, gastric, and esophagus.
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Affiliation(s)
- Ryouichi Tsunedomi
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan.
| | - Kiyoshi Yoshimura
- Showa University Clinical Research Institute for Clinical Pharmacology and Therapeutics, 1-5-8 Hatanodai, Shinagawa, Tokyo, 142-8555, Japan
| | - Nobuaki Suzuki
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan
| | - Shoichi Hazama
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan.,Faculty of Medicine, Department of Translational Research and Developmental Therapeutics against Cancer, Yamaguchi University, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan
| | - Hiroaki Nagano
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan
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Liao H, Xiong T, Peng J, Xu L, Liao M, Zhang Z, Wu Z, Yuan K, Zeng Y. Classification and Prognosis Prediction from Histopathological Images of Hepatocellular Carcinoma by a Fully Automated Pipeline Based on Machine Learning. Ann Surg Oncol 2020; 27:2359-2369. [PMID: 31916093 DOI: 10.1245/s10434-019-08190-1] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2019] [Indexed: 02/05/2023]
Abstract
OBJECTIVE The aim of this study was to develop quantitative feature-based models from histopathological images to distinguish hepatocellular carcinoma (HCC) from adjacent normal tissue and predict the prognosis of HCC patients after surgical resection. METHODS A fully automated pipeline was constructed using computational approaches to analyze the quantitative features of histopathological slides of HCC patients, in which the features were extracted from the hematoxylin and eosin (H&E)-stained whole-slide images of HCC patients from The Cancer Genome Atlas and tissue microarray images from West China Hospital. The extracted features were used to train the statistical models that classify tissue slides and predict patients' survival outcomes by machine-learning methods. RESULTS A total of 1733 quantitative image features were extracted from each histopathological slide. The diagnostic classifier based on 31 features was able to successfully distinguish HCC from adjacent normal tissues in both the test [area under the receiver operating characteristic curve (AUC) 0.988] and external validation sets (AUC 0.886). The random-forest prognostic model using 46 features was able to significantly stratify patients in each set into longer- or shorter-term survival groups according to their assigned risk scores. Moreover, the prognostic model we constructed showed comparable predicting accuracy as TNM staging systems in predicting patients' survival at different time points after surgery. CONCLUSIONS Our findings suggest that machine-learning models derived from image features can assist clinicians in HCC diagnosis and its prognosis prediction after hepatectomy.
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Affiliation(s)
- Haotian Liao
- Department of Liver Surgery and Liver Transplantation, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
| | - Tianyuan Xiong
- Department of Cardiology, West China Hospital, Sichuan University, Chengdu, China
| | - Jiajie Peng
- School of Computer Science, Northwestern Polytechnical University, Xi'an, China
| | - Lin Xu
- Department of Liver Surgery and Liver Transplantation, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
| | - Mingheng Liao
- Department of Liver Surgery and Liver Transplantation, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
| | - Zhen Zhang
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
| | - Zhenru Wu
- Laboratory of Pathology, Department of Pathology, West China Hospital, Sichuan University, Chengdu, China
| | - Kefei Yuan
- Department of Liver Surgery and Liver Transplantation, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China.
| | - Yong Zeng
- Department of Liver Surgery and Liver Transplantation, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China.
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Zhang L, Kuang S, Chen J, Zhang Y, Zhao B, Peng H, Xiao Y, Fowler K, Wang J, Sirlin CB. The Role of Preoperative Dynamic Contrast-enhanced 3.0-T MR Imaging in Predicting Early Recurrence in Patients With Early-Stage Hepatocellular Carcinomas After Curative Resection. Front Oncol 2019; 9:1336. [PMID: 31850221 PMCID: PMC6892896 DOI: 10.3389/fonc.2019.01336] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2019] [Accepted: 11/15/2019] [Indexed: 12/12/2022] Open
Abstract
Objectives: Liver resection is potentially curative for early-stage hepatocellular carcinoma (eHCC) in patients with well-preserved liver function. The prognosis of these patients after resection is still unsatisfactory because of frequent early recurrence (ER). Therefore, we investigated the role of preoperative dynamic contrast-enhanced 3.0-T MR imaging in predicting ER of eHCC after curative resection. Methods From May 2014 to October 2017, we retrospectively analyzed 82 patients with eHCC who underwent dynamic MR imaging and subsequently underwent curative resection. Liver Imaging Reporting and Data System (LI-RADS) v2018 major and ancillary imaging features, as well as two non-LI-RADS MR imaging features (irregular tumor margin and tumor number), were evaluated. A multivariate Cox regression analysis was used to identify independent predictors, and two models (preoperative and postoperative prediction models) were developed. Results ER was observed in 25 patients (25/82, 30.5%). In the univariate analyses, preoperative alpha-fetoprotein (AFP) level >200 ng/ml, three MR imaging features (multifocal tumors, corona enhancement, and irregular tumor margin), and microvascular invasion (MVI) were associated with ER. In the multivariate analysis, corona enhancement (hazard ratio [HR]: 2.970; p = 0.013) and irregular tumor margin (HR: 2.377; p = 0.048) were independent predictors in the preoperative prediction model, and preoperative AFP level >200 ng/ml (HR: 2.493; p = 0.044) plus corona enhancement (HR: 3.046; p = 0.014) were independent predictors in the postoperative prediction model (microvascular invasion [MVI] was not; p = 0.061). When combined with both predictors, the specificity for ER in the preoperative prediction model was 98.2% (56/57), which was comparable to that of the postoperative prediction model [96.7% (55/57)]. Conclusions Our results demonstrated that preoperative MR imaging features (corona enhancement and irregular tumor margin) have the potential to preoperatively identify high-risk ER patients with eHCC, with a specificity >90%.
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Affiliation(s)
- Linqi Zhang
- Department of Radiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Sichi Kuang
- Department of Radiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Jingbiao Chen
- Department of Radiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yao Zhang
- Department of Radiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Binliang Zhao
- Department of Radiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Hao Peng
- Department of Nuclear Medicine, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China
| | - Yuanqiang Xiao
- Department of Radiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Kathryn Fowler
- Liver Imaging Group, Department of Radiology, University of California, San Diego, La Jolla, CA, United States
| | - Jin Wang
- Department of Radiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Claude B Sirlin
- Liver Imaging Group, Department of Radiology, University of California, San Diego, La Jolla, CA, United States
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12
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Yue CX, Liu YX, Yun ZY, Li N, Zhao CJ, Wang RT. Decreased platelet distribution width predicts a worse prognosis in patients undergoing surgical resection for hepatocellular carcinoma. Cancer Biomark 2019; 26:361-366. [PMID: 31594211 DOI: 10.3233/cbm-190474] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Affiliation(s)
- Chen-Xi Yue
- Department of Internal Medicine, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang, China
- Department of Internal Medicine, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang, China
| | - Yu-Xi Liu
- Department of Internal Medicine, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang, China
- Department of Internal Medicine, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang, China
| | - Zhi-Yuan Yun
- Department of Internal Medicine, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang, China
| | - Na Li
- Department of Internal Medicine, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang, China
| | - Chang-Jiu Zhao
- Department of Nuclear Medicine, The First Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, China
| | - Rui-Tao Wang
- Department of Internal Medicine, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang, China
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Chen Z, Jian Z, Wu X, Wang J, Peng J, Lao X. Clinical conditions and treatment requirements for long-term survival among hepatitis B-related hepatocellular carcinoma initially treated with chemoembolization. Cancer Med 2019; 8:5097-5107. [PMID: 31313476 PMCID: PMC6718579 DOI: 10.1002/cam4.2380] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2019] [Revised: 06/14/2019] [Accepted: 06/17/2019] [Indexed: 12/17/2022] Open
Abstract
OBJECTIVE Transarterial chemoembolization (TACE) is recommended to treat intermediate/advanced stage of hepatocellular carcinoma (HCC). However, the overall survival among initially TACE-treated patients varies significantly. The clinical characterization of long-term survival following TACE remains uncertain. We sought to identify clinical parameters and treatment requirements for long-term survival among patients with hepatitis B-related HCC who were initially treated with TACE. MATERIALS AND METHODS The included patients with HCC were admitted to our cancer center between December 2009 and May 2015. Patients who survived for >3 years were compared with those who died within 3 years. The clinical and laboratory findings that were associated with the survival were also analyzed. RESULTS One in six (17.9%) patients with HCC in this cohort survived for > 3 years after TACE. Body mass index (BMI) ≥ 23kg/m2 , aspartate aminotransferase levels ≤ 40 U/L, an activated partial thromboplastin time ≤ 34 seconds, α-fetoprotein (AFP) levels ≤ 25 ng/mL, antiviral therapy, tumor size ≤ 8 cm, solitary nodule, and the absence of vascular invasion were independently favorably associated with a 3-year survival. An absence of vascular invasion was the only independent factor associated with 3-year survival in patients who received resection and/or ablation after TACE. CONCLUSION In this cohort, a 3-year survival was associated with BMI, antivirus treatment, tumor status, hepatic function, and AFP level. Distant metastasis did not negatively impact the long-term survival among patients with hepatitis B-related HCC initially treated with TACE. Vascular invasion was the single impediment to long-term survival in patients who received add-on resection and/or ablation after TACE.
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Affiliation(s)
- Zhen‐Xin Chen
- Department of Hepatobiliary and Pancreatic SurgerySun Yat‐sen University Cancer CenterGuangzhouP. R. China
- State Key Laboratory of Southern ChinaGuangzhouP. R. China
- Collaborative Innovation Center for Cancer MedicineGuangzhouP. R. China
| | - Zhi‐Wei Jian
- Department of Hepatobiliary and Pancreatic SurgerySun Yat‐sen University Cancer CenterGuangzhouP. R. China
- State Key Laboratory of Southern ChinaGuangzhouP. R. China
- Collaborative Innovation Center for Cancer MedicineGuangzhouP. R. China
| | - Xi‐Wen Wu
- Department of Hepatobiliary and Pancreatic SurgerySun Yat‐sen University Cancer CenterGuangzhouP. R. China
- State Key Laboratory of Southern ChinaGuangzhouP. R. China
- Collaborative Innovation Center for Cancer MedicineGuangzhouP. R. China
| | - Jun‐Cheng Wang
- Department of Hepatobiliary and Pancreatic SurgerySun Yat‐sen University Cancer CenterGuangzhouP. R. China
- State Key Laboratory of Southern ChinaGuangzhouP. R. China
- Collaborative Innovation Center for Cancer MedicineGuangzhouP. R. China
| | - Jing‐Yuan Peng
- Department of Hepatobiliary and Pancreatic SurgerySun Yat‐sen University Cancer CenterGuangzhouP. R. China
- State Key Laboratory of Southern ChinaGuangzhouP. R. China
- Collaborative Innovation Center for Cancer MedicineGuangzhouP. R. China
| | - Xiang‐Ming Lao
- Department of Hepatobiliary and Pancreatic SurgerySun Yat‐sen University Cancer CenterGuangzhouP. R. China
- State Key Laboratory of Southern ChinaGuangzhouP. R. China
- Collaborative Innovation Center for Cancer MedicineGuangzhouP. R. China
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Kobayashi Y, Kiya Y, Sugawara T, Nishioka Y, Hashimoto M, Shindoh J. Expanded Makuuchi's criteria using estimated indocyanine green clearance rate of future liver remnant as a safety limit for maximum extent of liver resection. HPB (Oxford) 2019; 21:990-997. [PMID: 30711244 DOI: 10.1016/j.hpb.2018.12.001] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2018] [Revised: 11/19/2018] [Accepted: 12/04/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND Recent advances in liver surgery have dramatically improved the safety of hepatectomy for hepatocellular carcinoma (HCC). The aim of this study was to compare outcomes for patients fulfilling an extended criteria vs. those fulfilling the conventional criteria based on the bilirubin and indocyanine green (ICG) clearance (Makuuchi's criteria). METHODS The short term outcomes of patients undergoing hepatectomy for HCC and who fulfilled the expanded criteria (ICG clearance of future remnant liver [ICG-Krem] ≥ 0.05 estimated using 3-D volumetry) were retrospectively reviewed and were compared between those fulfilling the conventional criteria. Postoperative hepatic insufficiency (PHI) was defined as peak total bilirubin >7 mg/dL. RESULTS A total of 323 patients undergoing resection of whom 269 (83%) met conventional criteria (In-M) and 54 (17%) extended criteria (Ex-M). The overall morbidity rates were not significantly different. The incidence of PHI was 0.37% in In-M and 3.7% in Ex-M (P = 0.074), with no liver-related deaths. When the ICG-Krem ≥ 0.05 criterion was included, major hepatectomy was performed in 24 patients (41%) in Ex-M with no significant increase in major morbidity (13%), PHI(3.3%), or liver-related death (0%) compared with minor hepatectomy (n = 30) in Ex-M(10%, 4% and 0%, respectively). CONCLUSIONS Objective criteria using ICG clearance rate and 3-D volumetry may offer opportunities for safe surgical resection in selected patients exceeding the conventional criteria.
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Affiliation(s)
- Yuta Kobayashi
- Hepato-Biliary-Pancreatic Surgery Division, Department of Gastroenterological Surgery, Toranomon Hospital, Japan
| | - Yoshitaka Kiya
- Hepato-Biliary-Pancreatic Surgery Division, Department of Gastroenterological Surgery, Toranomon Hospital, Japan
| | - Toshitaka Sugawara
- Hepato-Biliary-Pancreatic Surgery Division, Department of Gastroenterological Surgery, Toranomon Hospital, Japan
| | - Yujiro Nishioka
- Okinaka Memorial Institute for Medical Disease, Tokyo, Japan
| | - Masaji Hashimoto
- Hepato-Biliary-Pancreatic Surgery Division, Department of Gastroenterological Surgery, Toranomon Hospital, Japan
| | - Junichi Shindoh
- Hepato-Biliary-Pancreatic Surgery Division, Department of Gastroenterological Surgery, Toranomon Hospital, Japan; Okinaka Memorial Institute for Medical Disease, Tokyo, Japan.
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Incidence of Occult Intrahepatic Metastasis in Hepatocellular Carcinoma Treated With Transplantation Corresponds to Early Recurrence Rates After Partial Hepatectomy. Ann Surg 2019; 267:922-928. [PMID: 28085695 DOI: 10.1097/sla.0000000000002135] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVE This study aimed to compare the incidence of radiologically unrecognized (occult) hepatocellular carcinoma (HCC) lesions in explant hepatectomy specimens from orthotopic liver transplants (OLTs) performed for HCC with rates of HCC intrahepatic recurrence after resection. SUMMARY OF BACKGROUND DATA Resection of HCC is associated with high rates of intrahepatic HCC recurrence. However, it is unclear whether these recurrences represent incomplete resection of unrecognized metastatic lesions from the primary tumor or subsequent de novo tumor formation due to inherent biological proclivity for HCC formation. METHODS We collected patient, tumor, and pathology data on HCC patients treated surgically from 3696 OLTs in the Organ Procurement and Transplantation (OPTN) national database, 299 OLTs at a single transplant center, and 232 partial hepatectomies from a hepatobiliary cancer center. RESULTS In the OPTN and high-volume transplant center cohorts, 37% and 42% of patients had occult HCC lesions on explant pathology, respectively. Among cancer center patients, the 2-year recurrence rate was 46%, and 74% of patients who recurred presented with liver only recurrence. CONCLUSION Although the transplant and resection populations differ, occult multifocality is common in transplant explants and similar to the 46% early recurrence rate following partial hepatectomy. These data suggest that noncurative resection often results from occult intrahepatic multifocality present at the time of resection rather than a malignant predisposition of the remnant liver with de novo tumorigenesis.
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Hara K, Takeda A, Tsurugai Y, Saigusa Y, Sanuki N, Eriguchi T, Maeda S, Tanaka K, Numata K. Radiotherapy for Hepatocellular Carcinoma Results in Comparable Survival to Radiofrequency Ablation: A Propensity Score Analysis. Hepatology 2019; 69:2533-2545. [PMID: 30805950 DOI: 10.1002/hep.30591] [Citation(s) in RCA: 88] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2018] [Accepted: 02/06/2019] [Indexed: 12/19/2022]
Abstract
Potentially curative treatments for early-stage hepatocellular carcinoma (HCC) have drawbacks and contraindications. Recently, radiotherapy has achieved good outcomes. We compared the outcomes of radiotherapy and radiofrequency ablation (RFA) for early-stage HCC. Consecutive patients with ≤3 early-stage HCC lesions and tumor diameters ≤3 cm treated with RFA or radiotherapy were reviewed. RFA was the first choice for HCC unsuitable for surgery. Otherwise, stereotactic body radiotherapy in five fractions was mainly performed. For HCC adjacent to the gastrointestinal tract, radiotherapy with mild hypofractionation was performed. Propensity score matching was performed to reduce the selection bias between the RFA and radiotherapy groups. Between 2012 and 2016, a total of 231 patients with 474 tumors and 143 patients with 221 tumors were eligible and were treated with RFA and radiotherapy, respectively. In an unmatched comparison, the 3-year local recurrence rate was significantly lower for radiotherapy than for RFA (5.3%; 95% confidence interval [CI], 2.7-9.2; versus 12.9%, 95% CI, 9.9-16.2) (P < 0.01). A propensity score matching analysis of 106 patients in each group successfully matched the two treatment groups with regard to Barcelona Clinic Liver Cancer staging, T stage, and tumor size but not the adjacency of the tumor to risk organs or first or salvage treatment. The 3-year overall survival rates for RFA and radiotherapy patients were comparable (69.1%; 95% CI, 58.2-77.7; and 70.4%; 95% CI, 58.5-79.4, respectively; P = 0.86). Conclusion: Radiotherapy has excellent local control and comparable overall survival in patients with well-compensated liver function, exhibiting advantageous characteristics and compensating for the deficiencies of other treatment modalities; radiotherapy appears to be an acceptable alternative treatment option for patients who are not candidates for RFA.
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Affiliation(s)
- Koji Hara
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Atsuya Takeda
- Radiation Oncology Center, Ofuna Chuo Hospital, Kamakura, Japan
| | | | - Yusuke Saigusa
- Department of Biostatistics, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Naoko Sanuki
- Radiation Oncology Center, Ofuna Chuo Hospital, Kamakura, Japan
| | | | - Shin Maeda
- Division of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan
| | - Katsuaki Tanaka
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Kazushi Numata
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan
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Zhang W, Chen J, Liu L, Wang L, Liu J, Su D. Prognostic value of preoperative computed tomography in HBV-related hepatocellular carcinoma patients after curative resection. Onco Targets Ther 2019; 12:3791-3804. [PMID: 31190879 PMCID: PMC6529036 DOI: 10.2147/ott.s199136] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2018] [Accepted: 03/05/2019] [Indexed: 12/12/2022] Open
Abstract
Background: Preoperative treatments are considered for patients with worse outcome to improve overall survival and reduce tumor relapse. This study developed a prognostic risk estimation for patients with hepatitis B virus (HBV)-related solitary hepatocellular carcinoma after curative resection, including preoperative computed tomography (CT) signatures. Methods: Preoperative multiphasic CTs for 166 patients with operable HCC were performed in our hospital from 15 November 2013 through 15 May 2015. Follow-up information, until 5 June 2017, included: CT, pathological and clinical characteristics, and recurrence and metastases of HCC confirmed by pathological or radiological diagnosis. The parameters were analyzed by the Kaplan-Meier method and Cox proportional hazards regression analysis. Results: In multivariate analyses, overall survival was not significantly associated with any of the analyzed prognostic risk factors, but did show that the following were significant prognostic risk factors for disease-free survival: larger tumor size, positive radiogenomic venous invasion, non-smooth tumor margin, and histological microvascular invasion. These were all incorporated into the nomogram. The calibration curves for predicting the probability of disease-free survival between the nomogram and actual observation showed good conformity. Conclusion: In patients with HBV-related HCC, CT signatures were a noninvasive significant indicator of disease-free survival. Thus, consideration of CT signatures may optimize preoperative treatment strategies for the individual patient.
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Affiliation(s)
| | - Jie Chen
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People's Republic of China
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Huang X, Wan F, Ma L, Phan JB, Lim RX, Li C, Chen J, Deng J, Li Y, Chen W, He M. Investigation of copper-cysteamine nanoparticles as a new photosensitizer for anti-hepatocellular carcinoma. Cancer Biol Ther 2019; 20:812-825. [PMID: 30727796 DOI: 10.1080/15384047.2018.1564568] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a primary malignancy of the liver and occurs predominantly in patients with underlying chronic liver disease and cirrhosis. HCC is now the third leading cause of cancer deaths worldwide, with over 500,000 people affected. However, there is no complete effective (ideal) treatment for liver cancer yet, and the new methods are expected to be discovered. Herein, for the first time, we report the anti-HCC effects of copper-cysteamine nanoparticles (Cu-Cy NPs), a new type of photosensitizers. An in vitro 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay shows that Cu-Cy NPs could significantly reduce the activity of HepG2 cells at a very low dose after a short time of ultraviolet radiation. In addition, we found that cell death was induced by Cu-Cy NPs, which is associated with cellular apoptosis. This implied that apoptosis might be the main mechanism of the Cu-Cy's anti-HCC activity. Furthermore, we found that Cu-Cy NPs obviously inhibited the tumor growth in vivo. More interestingly, we found that the soluble Cu-Cy NPs were able to enter exosomes which were secreted by tumor cells, and exosomes could be used to deliver Cu-Cy NPs to target tumor cells. All these observations suggest that Cu-Cy NPs have a good potential for cancer treatment.
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Affiliation(s)
- Xuejing Huang
- a Department of Public Health School , Guangxi Medical University , Nanning , China
| | - Fengjie Wan
- a Department of Public Health School , Guangxi Medical University , Nanning , China
| | - Lun Ma
- b Department of Physics and the SAVANT Center , The University of Texas at Arlington , Arlington , TX , USA
| | - Jonathan B Phan
- b Department of Physics and the SAVANT Center , The University of Texas at Arlington , Arlington , TX , USA
| | - Rebecca Xueyi Lim
- b Department of Physics and the SAVANT Center , The University of Texas at Arlington , Arlington , TX , USA
| | - Cuiping Li
- a Department of Public Health School , Guangxi Medical University , Nanning , China
| | - Jiagui Chen
- a Department of Public Health School , Guangxi Medical University , Nanning , China
| | - Jinghuan Deng
- a Department of Public Health School , Guangxi Medical University , Nanning , China
| | - Yasi Li
- c College of Global Public Health , New York University , New York , NY , USA
| | - Wei Chen
- b Department of Physics and the SAVANT Center , The University of Texas at Arlington , Arlington , TX , USA
| | - Min He
- a Department of Public Health School , Guangxi Medical University , Nanning , China.,d Key Laboratory of High-Incidence-Tumor Prevention & Treatment (Guangxi Medical University) , Ministry of Education , Nanning , P.R. China.,e Department of Animal Center , Guangxi Medical University , Nanning , China
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Lurje G, Bednarsch J, Czigany Z, Amygdalos I, Meister F, Schöning W, Ulmer TF, Foerster M, Dejong C, Neumann UP. Prognostic factors of disease-free and overall survival in patients with hepatocellular carcinoma undergoing partial hepatectomy in curative intent. Langenbecks Arch Surg 2018; 403:851-861. [DOI: 10.1007/s00423-018-1715-9] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2018] [Accepted: 09/24/2018] [Indexed: 02/07/2023]
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Wei Y, Dai F, Yi Y, Ye W, Zhao W. Impact of local tumor lesion treatments and preoperative indicators on the survival of patients with small hepatocellular carcinomas. Oncol Lett 2018; 16:5050-5058. [PMID: 30250572 PMCID: PMC6144377 DOI: 10.3892/ol.2018.9263] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2017] [Accepted: 03/02/2018] [Indexed: 11/07/2022] Open
Abstract
The prognosis for small hepatocellular carcinomas (SHCC) remains uncertain. The aim of the present study was to compare three local tumor lesion treatments and identify the prognostic factors in patients with SHCC by analyzing preoperative indicators. A retrospective study was performed using data from 206 patients with SHCC from 2006–2015. All of the patients had undergone transarterial chemoembolization (TACE) alone, TACE plus percutaneous microwave coagulation therapy (PMCT) or surgical resection (SR). The Kaplan-Meier method was used to calculate the survival rates. Multivariate analysis was conducted using Cox regression analysis. The median survival time of patients with SHCC was 27 (range, 14–49) months in the TACE group, 29.5 (range, 16–52) months in the TACE-PMCT group and 36.5 (range, 26–52) months in the SR group (P=0.091). The 1, 3 and 5-year survival rates for patients with SHCC were 82.4, 64.9 and 46.8% in the TACE group; 89.0, 72.6 and 58.3% in the TACE-PMCT group and 88.8, 72.3 and 58.6% in the SR group (P=0.181), respectively. Analysis from the Cox regression model demonstrated that preoperative α-fetoprotein (AFP; <400 ng/ml vs. ≥400 ng/ml; HR=0.548; P=0.036) was an independent predictor of the survival time of patients with SHCC. Analysis of patients with preoperative AFP levels of ≥400 ng/ml revealed that the median survival time in the SR group was 36 (range, 28.25–52) months, significantly longer than the TACE (17 months; range, 12–44 months) and TACE-PMCT group (27 months; range, 14–55 months; P=0.035). The 1, 2 and 3-year survival rates for patients with SHCC with ≥400 ng/ml AFP were: 70.8, 55.5 and 49.9% in the TACE group; 83.7, 68.0 and 60.8% in the TACE-PMCT group; and 90.9, 81.8 and 61.0% in SR group, respectively (P=0.664). However, there was no significant difference among the three groups in the survival time of patients with SHCC with <400 ng/ml preoperative AFP. The observations indicated that SR is not significantly different for overall survival time in the patients with SHCC between the two groups; this method can be employed for patients with SHCC. This was based on the median survival time of patients with ≥400 ng/ml AFP in the SR group who had a longer survival time and a higher survival rate than in the TACE and TACE-PMCT group.
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Affiliation(s)
- Yanyan Wei
- Department of Liver Disease, The Second Hospital of Nanjing, Medical School of Southeast University, Nanjing, Jiangsu 210000, P.R. China
| | - Feng Dai
- Department of Liver Disease, The Second Hospital of Nanjing, Medical School of Southeast University, Nanjing, Jiangsu 210000, P.R. China
| | - Yongxiang Yi
- Department of Liver Disease, The Second Hospital of Nanjing, Medical School of Southeast University, Nanjing, Jiangsu 210000, P.R. China
| | - Wei Ye
- Department of Liver Disease, The Second Hospital of Nanjing, Medical School of Southeast University, Nanjing, Jiangsu 210000, P.R. China
| | - Wei Zhao
- Department of Liver Disease, The Second Hospital of Nanjing, Medical School of Southeast University, Nanjing, Jiangsu 210000, P.R. China
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Nakano R, Ohira M, Kobayashi T, Ide K, Tahara H, Kuroda S, Shimizu S, Kimura T, Nagata Y, Aikata H, Chayama K, Ohdan H. Hepatectomy versus stereotactic body radiotherapy for primary early hepatocellular carcinoma: A propensity-matched analysis in a single institution. Surgery 2018; 164:219-226. [PMID: 29801728 DOI: 10.1016/j.surg.2018.03.006] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2017] [Revised: 02/14/2018] [Accepted: 03/10/2018] [Indexed: 12/20/2022]
Abstract
OBJECTIVE To evaluate the efficacy of both surgical resection and stereotactic body radiotherapy for small hepatocellular carcinoma. BACKGROUND Although the number of stereotactic body radiotherapies being performed for hepatocellular carcinoma has gradually increased, data comparing surgical resection and stereotactic body radiotherapy are limited. METHODS Between 2008 and 2015, a total of 281 patients with 1 to 3 small hepatocellular carcinoma tumors (≤3 cm in diameter), treated initially with curative intent (surgical resection, 254; stereotactic body radiotherapy, 27), were retrospectively analyzed. Overall survival and disease-free survival were compared in a propensity score matching analysis. RESULTS Patients in the surgical resection group tended to be younger, had more tumors, and had better hepatic function than those in the stereotactic body radiotherapy group (P < .05). The percent recurrence of the same sub-segment in the stereotactic body radiotherapy group was significantly higher than that in the surgical resection group (P = .0034). Propensity score analysis revealed that 54 patients with surgical resection and 27 with stereotactic body radiotherapy had the same baseline characteristics. The 5-year overall survival and disease-free survival rates for the surgical resection and stereotactic body radiotherapy groups were 75.2% vs 47.8% (P = .0149) and 33.8% vs 16.4% (P = .0512), respectively. Multivariate analysis showed that surgical resection was a significant favorable factor for overall survival and disease-free survival of patients with one to three small hepatocellular carcinomas. CONCLUSION Surgical resection provided better long-term overall survival and disease-free survival in patients with small hepatocellular carcinoma tumors. However, stereotactic body radiotherapy may be an effective alternative treatment for inoperable patients with early hepatocellular carcinoma.
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Affiliation(s)
- Ryosuke Nakano
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Japan; Liver Research Project Center, Hiroshima University, Japan
| | - Masahiro Ohira
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Japan; Liver Research Project Center, Hiroshima University, Japan; Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Japan.
| | - Tsuyoshi Kobayashi
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Japan; Liver Research Project Center, Hiroshima University, Japan
| | - Kentaro Ide
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Japan; Liver Research Project Center, Hiroshima University, Japan
| | - Hiroyuki Tahara
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Japan; Liver Research Project Center, Hiroshima University, Japan
| | - Shintaro Kuroda
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Japan; Liver Research Project Center, Hiroshima University, Japan
| | - Seiichi Shimizu
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Japan; Liver Research Project Center, Hiroshima University, Japan
| | - Tomoki Kimura
- Department of Radiation Oncology, Institute of Biomedical & Health Sciences, Hiroshima University, Japan
| | - Yasushi Nagata
- Department of Radiation Oncology, Institute of Biomedical & Health Sciences, Hiroshima University, Japan
| | - Hiroshi Aikata
- Liver Research Project Center, Hiroshima University, Japan; Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Japan
| | - Kazuaki Chayama
- Liver Research Project Center, Hiroshima University, Japan; Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Japan
| | - Hideki Ohdan
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Japan; Liver Research Project Center, Hiroshima University, Japan
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22
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How we approach it: treatment options for hepatocellular carcinoma. Am J Gastroenterol 2018; 113:791-794. [PMID: 29713029 DOI: 10.1038/s41395-018-0008-9] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2017] [Accepted: 11/21/2017] [Indexed: 12/11/2022]
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Yang C, Su H, Liao X, Han C, Yu T, Zhu G, Wang X, Winkler CA, O'Brien SJ, Peng T. Marker of proliferation Ki-67 expression is associated with transforming growth factor beta 1 and can predict the prognosis of patients with hepatic B virus-related hepatocellular carcinoma. Cancer Manag Res 2018; 10:679-696. [PMID: 29692627 PMCID: PMC5901156 DOI: 10.2147/cmar.s162595] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the most frequent malignancy of the liver. Transforming growth factor beta 1 (TGFB1) and marker of proliferation Ki-67 (MKI67) regulate cell proliferation, differentiation, and growth. The association between MKI67 and TGFB1 expression and its clinical implications in HCC remain unknown.
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Affiliation(s)
- Chengkun Yang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, China
| | - Hao Su
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, China
| | - Xiwen Liao
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, China
| | - Chuangye Han
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, China
| | - Tingdong Yu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, China
| | - Guangzhi Zhu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, China
| | - Xiangkun Wang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, China
| | - Cheryl Ann Winkler
- Basic Research Laboratory, CCR, NCI, Leidos Biomedical Research, Frederick National Laboratory, Frederick, MD, USA
| | - Stephen J O'Brien
- Laboratory of Genomic Diversity, National Cancer Institute, NIH, Frederick, MD, USA.,Theodosius Dobzhansky Center for Genome Bioinformatics, St. Petersburg State University, St Petersburg, Russia.,Guy Harvey Oceanographic Center, Halmos College of Natural Sciences and Oceanography, Nova Southeastern University, Fort Lauderdale, FL, USA
| | - Tao Peng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, China
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Benzoni E, Lorenzin D, Favero A, Adani G, Baccarani U, Molaro R, Zompicchiatti A, Saccomano E, Avellini C, Bresadola F, Uzzau A. Liver Resection for Hepatocellular Carcinoma: a Multivariate Analysis of Factors Associated with Improved Prognosis. the Role of Clinical, Pathological and Surgical Related Factors. TUMORI JOURNAL 2018; 93:264-8. [PMID: 17679461 DOI: 10.1177/030089160709300306] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Aims and background Hepatocellular carcinoma (Hcc) is the third most common cause of cancer death. The aim of this study is to examine the factors associated with improved prognosis in Hcc after liver resection. Patients and methods From September 1989 to March 2005, 134 consecutive patients had liver resection for Hcc on cirrhosis at our department. We performed 54 major liver resections and 80 limited resections. All patients enrolled in the study were followed-up three times during the first year after resection and twice the next years. Results In-hospital mortality rate was 7.4%, about 50% of these cases were Child-Pugh B patients. Morbidity rate was 47.7%, caused by the rising of ascites, temporary liver impairment function, biliary fistula, hepatic abscess, hemoperitoneum and pleural effusion. Overall survival resulted to be influenced by etiology (P = 0.03), underlying liver disease, in particular Child A vs BC (P = 0.04), Endmondson-Steiner grading (P = 0.01), the absence of a capsule (P = 0.004), the presence of more than one lesion (P = 0.02), lesion's size over 5 cm (P = 0.04), Pringle maneuver length over than 20 minutes (P = 0.03), an amount of resected liver volume lesser than 50% of total liver volume (P = 0. 03), and the relapse of Hcc (P = 0.01). Conclusions The treatment of hepatocellular carcinoma should be both the most radical to obtain the best outcome and to reduce the recurrence's rate, and the most suitable according to the patient's condition, lesion's characteristics and underlying liver disease: because of the large number of factors affecting the outcome of Hcc, unfortunately, we are still far from an agreement upon a group of criteria useful to select the best candidates for liver resection.
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Affiliation(s)
- Enrico Benzoni
- Department of Surgery, School of Medicine, University of Udine, Udine, Italy.
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Yang C, Wang X, Liao X, Han C, Yu T, Qin W, Zhu G, Su H, Yu L, Liu X, Lu S, Chen Z, Liu Z, Huang K, Liu Z, Liang Y, Huang J, Xiao K, Peng M, Winkle CA, O'Brien SJ, Peng T. Aldehyde dehydrogenase 1 (ALDH1) isoform expression and potential clinical implications in hepatocellular carcinoma. PLoS One 2017; 12:e0182208. [PMID: 28792511 PMCID: PMC5549701 DOI: 10.1371/journal.pone.0182208] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2017] [Accepted: 07/16/2017] [Indexed: 01/01/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most prevalent and life-threatening malignancies worldwide. There are few diagnostic and prognostic biomarkers and druggable targets for HCC. Aldehyde dehydrogenase 1 (ALDH1) is a marker of stem cells in a variety of cancers, but the mRNA levels and prognostic value of ALDH1 isoforms in HCC patients remain unknown. In the present study, gene ontology annotation of the ALDH1 family was performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID), and the gene pathway analsis was performed using GeneMANIA software. The initial prognostic value of ALDH1 expression in 360 HCC patients was assessed using the OncoLnc database. The expression levels of ALDH1 isoforms in normal liver tissues and clinical specimens of cancer vs. normal control datasets were determined using the GTEx and Oncomine databases, respectively. We then analyzed the prognostic value of ALDH1 expression in 212 hepatitis B virus (HBV)-related HCC patients using the GEO database. We found that the ALDH1 isoform showed high aldehyde dehydrogenase activity. The ALDH1A1, ALDH1B1, and ALDH1L1 genes encoded for the ALDH1 enzyme. High ALDH1B1 expression had protective qualities in HCC patients. Moreover, HBV-related HCC patients who showed high ALDH1L1 gene expression had a better clinical outcomes. In addition, high ALDH1A1 expression was associated with a 57-month recurrence-free survival in HBV-related HCC patients. High ALDH1B1 expression was protective for HCCs with multiple nodules and high serum alpha-fetoprotein (AFP) level. Furthermore, high serum AFP levels contributed to lower ALDH1L1. ALDH1A1, ALDH1B1, and ALDH1L1, all of which were considered promising diagnostic and prognostic markers as well as potential drug targets.
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Affiliation(s)
- Cheng–kun Yang
- Department of Hepatobiliary Surgery, The first Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, China
| | - Xiang–kun Wang
- Department of Hepatobiliary Surgery, The first Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, China
| | - Xi–wen Liao
- Department of Hepatobiliary Surgery, The first Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, China
| | - Chuang–ye Han
- Department of Hepatobiliary Surgery, The first Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, China
| | - Ting–dong Yu
- Department of Hepatobiliary Surgery, The first Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, China
| | - Wei Qin
- Department of Hepatobiliary Surgery, The first Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, China
| | - Guang–zhi Zhu
- Department of Hepatobiliary Surgery, The first Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, China
| | - Hao Su
- Department of Hepatobiliary Surgery, The first Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, China
| | - Long Yu
- Department of Hepatobiliary and Pancreatic Surgery, The first Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
| | - Xiao–guang Liu
- Department of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong Province, China
| | - Si–cong Lu
- Department of Hepatobiliary Surgery, The first Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, China
| | - Zhi–wei Chen
- Department of Hepatobiliary Surgery, The first Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, China
| | - Zhen Liu
- Department of Hepatobiliary Surgery, The first Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, China
| | - Ke–tuan Huang
- Department of Hepatobiliary Surgery, The first Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, China
| | - Zheng–tao Liu
- Department of Hepatobiliary Surgery, The first Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, China
| | - Yu Liang
- Department of Hepatobiliary Surgery, The first Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, China
| | - Jian–lu Huang
- Department of Hepatobiliary Surgery, Third Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, China
| | - Kai–yin Xiao
- Department of Hepatobiliary Surgery, The first Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, China
| | - Min–hao Peng
- Department of Hepatobiliary Surgery, The first Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, China
| | - Cheryl Ann Winkle
- Laboratory of Genomic Diversity, National Cancer Institute, NIH, Frederick, MD, United States of America
| | - Stephen J. O'Brien
- Laboratory of Genomic Diversity, National Cancer Institute, NIH, Frederick, MD, United States of America
| | - Tao Peng
- Department of Hepatobiliary Surgery, The first Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, China
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CT-based radiomics signature: a potential biomarker for preoperative prediction of early recurrence in hepatocellular carcinoma. Abdom Radiol (NY) 2017; 42:1695-1704. [PMID: 28180924 DOI: 10.1007/s00261-017-1072-0] [Citation(s) in RCA: 158] [Impact Index Per Article: 19.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
PURPOSE To develop a CT-based radiomics signature and assess its ability for preoperatively predicting the early recurrence (≤1 year) of hepatocellular carcinoma (HCC). METHODS A total of 215 HCC patients who underwent partial hepatectomy were enrolled in this retrospective study, and all the patients were followed up at least within 1 year. Radiomics features were extracted from arterial- and portal venous-phase CT images, and a radiomics signature was built by the least absolute shrinkage and selection operator (LASSO) logistic regression model. Preoperative clinical factors associated with early recurrence were evaluated. A radiomics signature, a clinical model, and a combined model were built, and the area under the curve (AUC) of operating characteristics (ROC) was used to explore their performance to discriminate early recurrence. RESULTS Twenty-one radiomics features were chosen from 300 candidate features to build a radiomics signature that was significantly associated with early recurrence (P < 0.001), and they presented good performance in the discrimination of early recurrence alone with an AUC of 0.817 (95% CI: 0.758-0.866), sensitivity of 0.794, and specificity of 0.699. The AUCs of the clinical and combined models were 0.781 (95% CI: 0.719-0.834) and 0.836 (95% CI: 0.779-0.883), respectively, with the sensitivity being 0.784 and 0.824, and the specificity being 0.619 and 0.708, respectively. Adding a radiomics signature into conventional clinical variables can significantly improve the accuracy of the preoperative model in predicting early recurrence (P = 0.01). CONCLUSIONS The radiomics signature was a significant predictor for early recurrence in HCC. Incorporating radiomics signature into conventional clinical factors performed better for preoperative estimation of early recurrence than with clinical variables alone.
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He C, Peng W, Li C, Wen TF. Thymalfasin, a promising adjuvant therapy in small hepatocellular carcinoma after liver resection. Medicine (Baltimore) 2017; 96:e6606. [PMID: 28422855 PMCID: PMC5406071 DOI: 10.1097/md.0000000000006606] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
There is limited information available concerning the effect of thymalfasin (Tα1) as an adjuvant therapy in hepatocellular carcinoma (HCC) patient who received liver resection. The present study aimed to evaluate whether Tα1 can improve the prognosis of small HCC patients after liver resection.A total of 206 patients with small HCC who underwent liver resection were analyzed in our retrospective cohort study. Patients were divided into 2 groups: group A (resection + Tα1, n = 44) and group B (resection, n = 162). Clinical data, overall survival (OS), and recurrence-free survival (RFS) were compared. Prognostic factors were identified using multivariate analysis.After a median follow-up of 47.0 months, 134 patients (65%) had recurrence, and 62 patients (30.09%) died. The 1, 3, and 5-year OS rate of patients in group A was 97.7%, 90.6%, and 82.9%, respectively, and 95.1%, 80.5%, and 62.9%, respectively, for patients in group B (P = .014). The 1, 3, and 5-year RFS rate of patients in group A was 70.5%, 56.8%, and 53.3%, respectively, and 65.8%, 41.3%, and 32.1%, respectively, for patients in group B (P = .015). Multivariate analysis indicated that Tα1 was an independent prognostic factor for both OS (P = .015, hazard ratio 0.349, 95% confidence interval 0.149-0.816) and RFS (P = .019, hazard ratio 0.564, 95% confidence interval 0.349-0.910).Tα1 as an adjuvant therapy after liver resection may improve the prognosis of small HCC patients after liver resection.
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Park JG, Park SY, Tak WY, Kweon YO, Jang SY, Lee YR, Hur K, Lee HJ, Lee HW. Early complications after percutaneous radiofrequency ablation for hepatocellular carcinoma: an analysis of 1,843 ablations in 1,211 patients in a single centre: experience over 10 years. Clin Radiol 2017; 72:692.e9-692.e15. [PMID: 28364952 DOI: 10.1016/j.crad.2017.03.001] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2016] [Revised: 01/24/2017] [Accepted: 03/01/2017] [Indexed: 12/12/2022]
Abstract
AIM To evaluate the incidence of adverse events and associated factors after radiofrequency ablation (RFA) in patients with hepatocellular carcinoma within 30 days. MATERIALS AND METHODS The early complications that occurred within 30 days after RFA at a single institution from January 2000 to July 2010 were reviewed in order to evaluate the morbidity, mortality, and risk factors associated with the complications. In total, 1,211 patients (845 men, 70.5%) with a mean age of 68 years (range, 27-88 years) underwent 1,843 RFA procedures. RESULTS The overall incidence rate of complications was 6.8% (125 cases). Major complications (n=36, 2%) included liver abscess (n=15, 0.8%), intraperitoneal bleeding (n=8, 0.4%), liver failure (n=5, 0.3%), variceal bleeding (n=3, 0.2%), haemothorax (n=2, 0.1%), cholecystitis (n=2, 0.1%), and bowel perforation (n=1, 0.1%). Among the minor complications (n=89, 4.8%), the most common was the post RFA syndrome accompanied by pain and fever (n=75, 4.1%). Other minor complications included significant pleural effusion (n=7, 0.4%), skin wound infection (n=4, 0.2%), and thermal injuries to the skin (n=3, 0.2%). Procedural infections significantly increased with tumour size (OR=1.379; 95% confidence interval [CI], 1.191-1.579; p<0.001), and multiple overlapping ablations (OR=1.118; 95% CI, 1.019-1.227, p=0.018). Thrombocytopenia (<50,000/μl), prothrombin time, and serum albumin level were significantly associated with post-RFA bleeding episodes (p=0.041, p=0.021, and p=0.003, respectively). The overall mortality rate was 0.3% (three cases of hepatic failure, two case of sepsis, and one case of renal failure). CONCLUSIONS RFA is a safe and effective local treatment for hepatocellular carcinoma. Careful selection of patients and appropriate RFA planning could decrease procedural mortality and morbidity.
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Affiliation(s)
- J G Park
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Yeungnam University, Daegu, Republic of Korea
| | - S Y Park
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
| | - W Y Tak
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
| | - Y O Kweon
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - S Y Jang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Y R Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - K Hur
- Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - H J Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Yeungnam University, Daegu, Republic of Korea
| | - H W Lee
- Department of Pathology, Dongsan Medical Center, School of Medicine, Keimyung University, Daegu, Republic of Korea
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Reinterpretation of Outside Hospital MRI Abdomen Examinations in Patients With Cirrhosis: Is the OPTN Mandate Necessary? AJR Am J Roentgenol 2016; 207:782-788. [DOI: 10.2214/ajr.16.16209] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
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Oyama K, Kanki K, Shimizu H, Kono Y, Azumi J, Toriguchi K, Hatano E, Shiota G. Impact of Preferentially Expressed Antigen of Melanoma on the Prognosis of Hepatocellular Carcinoma. Gastrointest Tumors 2016; 3:128-135. [PMID: 28611979 DOI: 10.1159/000448137] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2016] [Accepted: 06/24/2016] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Retinoids, vitamin A and its derivatives, have an antitumor effect on hepatocellular carcinoma (HCC). The function of retinoids is exerted by the complex of retinoic acid (RA) with the heterodimer of retinoid X receptor and the RA receptor. The preferentially expressed antigen of melanoma (PRAME) acts as a dominant repressor of RA signaling by binding to the complex. The significance of PRAME on the prognosis of HCC remains to be clarified. METHODS PRAME mRNA expression was examined by quantitative real-time polymerase chain reaction in both tumor and non-tumor tissues of 100 HCC patients who received surgical resection. The effect of PRAME knockdown on DR5-mediated RA transcriptional activity was examined. RESULTS In tumor tissues, there were significant associations among PRAME expression, clinical stage, tumor markers, and tumor numbers. In non-tumor tissues, there were significant associations among PRAME expression, overall survival, and disease-free survival. The knockdown of PRAME caused no reduction in DR5-mediated transcriptional activity of RA, suggesting that PRAME acts via other mechanisms than the DR5 RA-responsive elements. CONCLUSION Our findings indicate that PRAME expression is a novel prognostic marker in HCC patients.
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Affiliation(s)
- Kenji Oyama
- Tottori University Hospital Cancer Center, Tottori University, Yonago, Japan.,Division of Molecular and Genetic Medicine, Department of Genetic Medicine and Regenerative Therapeutics, Graduate School of Medicine, Tottori University, Yonago, Japan
| | - Keita Kanki
- Division of Molecular and Genetic Medicine, Department of Genetic Medicine and Regenerative Therapeutics, Graduate School of Medicine, Tottori University, Yonago, Japan.,Department of Biomedical Engineering, Faculty of Engineering, Okayama University of Science, Okayama, Japan
| | - Hiroki Shimizu
- Division of Molecular and Genetic Medicine, Department of Genetic Medicine and Regenerative Therapeutics, Graduate School of Medicine, Tottori University, Yonago, Japan
| | - Yohei Kono
- Division of Molecular and Genetic Medicine, Department of Genetic Medicine and Regenerative Therapeutics, Graduate School of Medicine, Tottori University, Yonago, Japan
| | - Junya Azumi
- Division of Molecular and Genetic Medicine, Department of Genetic Medicine and Regenerative Therapeutics, Graduate School of Medicine, Tottori University, Yonago, Japan
| | - Kan Toriguchi
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Etsuro Hatano
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Goshi Shiota
- Division of Molecular and Genetic Medicine, Department of Genetic Medicine and Regenerative Therapeutics, Graduate School of Medicine, Tottori University, Yonago, Japan
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Li J, Zhou J, Yang PH, Xia Y, Shi YH, Wu D, Lv G, Zheng W, Wang K, Wan XY, Lau WY, Wu MC, Fan J, Shen F. Nomograms for survival prediction in patients undergoing liver resection for hepatitis B virus related early stage hepatocellular carcinoma. Eur J Cancer 2016; 62:86-95. [DOI: 10.1016/j.ejca.2016.04.011] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2015] [Revised: 04/10/2016] [Accepted: 04/18/2016] [Indexed: 01/06/2023]
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Liu W, Wang N, Lu M, Du XJ, Xing BC. MBD2 as a novel marker associated with poor survival of patients with hepatocellular carcinoma after hepatic resection. Mol Med Rep 2016; 14:1617-23. [PMID: 27315121 PMCID: PMC4940051 DOI: 10.3892/mmr.2016.5404] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2015] [Accepted: 05/31/2016] [Indexed: 01/17/2023] Open
Abstract
Methyl-CpG binding domain 2 (MBD2) leads to the silencing of methylated genes in cancer cells and was implicated in the activation of prometastatic genes in hepatocellular carcinoma (HCC). The present study aimed to investigate the expression status of MBD2 in HCC and the correlation with surgical outcomes. The correlation between clinical prognostic factors and MBD2 were also evaluated. MBD2 expression was analyzed by western blotting in 20 paired HCC and paratumor liver (PTL) tissues. In addition, immunohistochemistry was performed on the 159 HCC samples following hepatic resection performed between January 2003 and October 2008. The correlation between clinicopathological factors and MBD2 expression was also evaluated by statistical analysis to determine the prognostic value of MBD2 expression in HCC. Postoperative prognostic factors were evaluated using univariate and multivariate analyses. Compared with PTL tissues, MBD2 expression was shown to be upregulated in 10 of the 20 HCC tissues (50%) by western blotting. The immunohistochemistry data indicated significant increase of the MBD2 expression level in 81 cases (50.94%) compared with the PTL tissues (0/159, 0%, P<0.001). The upregulated MBD2 expression in HCC tissues was correlated with BCLC stage B, tumor size >5 cm and microscopic vascular invasion. Multivariate analysis revealed that MBD2 was an independent prognostic factor for overall survival [HR, 2.089; P=0.001] and disease-free survival (HR, 1.601; P=0.022). In conclusion, MBD2 expression was elevated in HCC tissue, which suggesting MBD2 as a candidate prognostic marker of HCC.
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Affiliation(s)
- Wei Liu
- Hepatopancreatobiliary Surgery Department Ⅰ, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing 100142, P.R. China
| | - Na Wang
- Hepatopancreatobiliary Surgery Department Ⅰ, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing 100142, P.R. China
| | - Min Lu
- Department of Cell Biology and Cancer Research Center, Peking University Health Science Center, Beijing 100083, P.R. China
| | - Xiao-Juan Du
- Department of Cell Biology and Cancer Research Center, Peking University Health Science Center, Beijing 100083, P.R. China
| | - Bao-Cai Xing
- Hepatopancreatobiliary Surgery Department Ⅰ, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing 100142, P.R. China
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Jin Y, Zhou L, Liang ZY, Jin KM, Zhou WX, Xing BC. Clinicopathologic and Prognostic Significance of Carboxyl Terminus of Hsp70-interacting Protein in HBV-related Hepatocellular Carcinoma. Asian Pac J Cancer Prev 2016; 16:3709-13. [PMID: 25987026 DOI: 10.7314/apjcp.2015.16.9.3709] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Many factors, including molecular ones, were demonstrated to be associated with long-term prognosis of hepatocellular carcinoma (HCC). Thus far, the expression and clinicopathologic and prognostic significance of the carboxyl terminus of Hsp70-interacting protein (CHIP) in B-type hepatitis virus (HBV)- related HCC remain unknown. MATERIALS AND METHODS CHIP expression was detected by immunohistochemical staining of surgical samples from 79 patients with HCC with HBsAg positivity. In addition, correlations with clinicopathologic parameters and patient survival were evaluated. RESULTS It was found that positive CHIP staining was observed in tumor, but not non-tumor, tissues. High expression of CHIP was significantly related to larger tumor size, with marginally significant associations noted for presence of portal vein invasion and higher serum a-fetoprotein level. In addition, univariate analysis showed that high CHIP expression was a powerful predictor for dismal overall and disease-free survival. However, independent prognostic implications of CHIP were not proven in multivariate Cox regression test. CONCLUSIONS CHIP is overexpressed in HBV-related HCC and is associated with unfavorable biological behavior as well as poor prognosis. However, its prognostic role needs to be further validated.
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Affiliation(s)
- Ye Jin
- Clinical Research Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, China E-mail :
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Liu J, Liu JF, Wang K, Yan ZL, Wan XY, Huang AM, Wang YZ, Li J, Xia Y, Shi LH, Jiao BH, Zhang Y, Shen F. Loss of function of Notch1 identifies a poor prognosis group of early stage hepatocellular carcinoma following hepatectomy. Oncol Rep 2015; 34:3174-86. [PMID: 26398566 DOI: 10.3892/or.2015.4300] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2015] [Accepted: 08/10/2015] [Indexed: 11/06/2022] Open
Abstract
Notch1 has previously been implicated in the carcinogenesis of hepatocellular carcinoma (HCC). The present study aimed to investigate the prognostic value of Notch1 in early stage HCC patients after hepatectomy. The differential expression of Notch1 in paired tumor and non-tumorous tissue was evaluated by RT-PCR, western blotting and immunohistochemistry. The correlation between Notch1 expression and the surgical outcome of patients at BCLC stage 0/A and its ≤5 cm subgroup was retrospectively investigated in 206 patients from the Eastern Hepatobiliary Surgery Hospital (training cohort), and prospectively validated in 185 patients from the same center and retrospectively verified in 129 patients from the Fujian Medical University (validation cohort 1 and 2, respectively). Compared with paired non-tumorous tissues, loss of Notch1 was observed in tumor tissue. Patients with normal Notch1 had better prognosis than those with loss of Notch1 in the training cohort and ≤5 cm subgroup (time to recurrence: 38.5±6.1 vs. 16.0±3.2 months, P<0.001 and 53.0±6.1 vs. 21.7±3.5 months, P=0.004; 1-, 3-, 5-year survival rates: 91, 64 and 49% vs. 73, 31 and 22%, P<0.001 and 93, 71, 57% vs. 76, 39, 24%, P<0.001). Notch1 expression was an independent factor for recurrence and survival (hazard ratio: 1.901, 2.154; 2.038 and 2.337). Moreover, Notch1 status affected early tumor recurrence, as the 2-year recurrence rate was 61.2 vs. 26.9% (P<0.001) and 51.2 vs. 21.3% (P=0.002) in tumors with reduced or increased Notch1 expression in this cohort and subgroup. These results were fully confirmed by the study in our prospective and retrospective validation cohorts. The status of Notch1 is useful for predicting the prognosis of patients with early stage HCC undergoing hepatectomy.
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Affiliation(s)
- Jian Liu
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, P.R. China
| | - Jing-Feng Liu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, P.R. China
| | - Kui Wang
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, P.R. China
| | - Zhen-Lin Yan
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, P.R. China
| | - Xu-Ying Wan
- Department of Clinical Database, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, P.R. China
| | - Ai-Min Huang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, P.R. China
| | - Yi-Zhou Wang
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, P.R. China
| | - Jun Li
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, P.R. China
| | - Yong Xia
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, P.R. China
| | - Le-Hua Shi
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, P.R. China
| | - Bing-Hua Jiao
- Department of Biochemistry and Molecular Biology, Second Military Medical University, Shanghai, P.R. China
| | - Yongjie Zhang
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, P.R. China
| | - Feng Shen
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, P.R. China
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Lu J, Xiong XZ, Li FY, Ye H, Lin YX, Zhou RX, Cai YL, Jin YW, Cheng NS. Prognostic Significance of Sarcomatous Change in Patients with Hepatocellular Carcinoma After Surgical Resection. Ann Surg Oncol 2015; 22 Suppl 3:S1048-56. [PMID: 26286198 DOI: 10.1245/s10434-015-4818-3] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2015] [Indexed: 02/05/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) with sarcomatous change (SC) is a rare malignancy associated with high aggressiveness and poor prognosis; however, its prognostic significance remains unclear. METHODS From January 1994 to April 2012, surgically resected HCCs with SC (n = 52) at West China Hospital were retrospectively reviewed. HCC with SC was defined as the concomitant presence of the sarcomatous component occupying at least 10 % (but not predominantly) of the HCC-bearing tissue. To validate its prognostic significance, we compared the clinicopathological features and survival rates of these patients with a cohort of 214 randomly selected ordinary HCC patients during the same period. RESULTS The clinicopathological characteristics of HCC with SC were similar to those of ordinary HCC, with the exception of capsule formation, adjacent organ invasion, lymph node metastasis, and TNM staging. A total of 45 (86.5 %) HCC patients with SC experienced a recurrence, with a median time to recurrence of 6.0 months. Overall survival (OS) rates in the sarcomatous HCC group at 1, 2, and 3 years were 55.8, 25, and 17.3 %, respectively, which were significantly lower than those in the ordinary HCC group (p < 0.001). On multivariable analysis, macrovascular invasion, satellite nodules, and R1/R2 resection were identified as independent risk factors for shorter disease-free survival and OS. CONCLUSIONS The presence of SC in HCC was uncommon, and was associated with much poorer prognosis than ordinary HCC. Radical resection with negative margin is essential for improving the prognosis. Future prospective studies are warranted to determine if recurrent patients can benefit from postoperative adjuvant therapies.
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Affiliation(s)
- Jiong Lu
- Department of Bile Duct Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Xian-Ze Xiong
- Department of Bile Duct Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Fu-Yu Li
- Department of Bile Duct Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Hui Ye
- Department of Bile Duct Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Yi-Xin Lin
- Department of Bile Duct Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Rong-Xing Zhou
- Department of Bile Duct Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Yu-Long Cai
- Department of Bile Duct Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Yan-Wen Jin
- Department of Bile Duct Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Nan-Sheng Cheng
- Department of Bile Duct Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
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Wu CH, Ho MC, Jeng YM, Liang PC, Hu RH, Lai HS, Shih TTF. Assessing hepatic fibrosis: comparing the intravoxel incoherent motion in MRI with acoustic radiation force impulse imaging in US. Eur Radiol 2015; 25:3552-9. [PMID: 25991478 DOI: 10.1007/s00330-015-3774-4] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2014] [Revised: 03/27/2015] [Accepted: 04/07/2015] [Indexed: 12/21/2022]
Abstract
OBJECTIVES This study compared the diagnostic performance of intravoxel incoherent motion (IVIM) in magnetic resonance imaging (MRI) and acoustic radiation force impulse imaging (ARFI) in ultrasound (US) for liver fibrosis (LF) evaluation. METHODS A total of 49 patients scheduled for liver surgery were recruited. LF in the non-tumorous liver parenchyma at the right lobe was estimated using a slow diffusion coefficient, fast diffusion coefficient (D fast), perfusion fraction (f) of the IVIM parameters, the total apparent diffusion coefficient of conventional diffusion-weighted imaging and the shear wave velocity (Vs) of ARFI. LF was graded using the Metavir scoring system on histological examination. The Spearman rank correlation coefficient for correlation and analysis of variance was used for determining difference. The diagnostic performance was compared using receiver operating characteristic curve analysis. RESULTS LF exhibited significant correlation with the three parameters D fast, f, and Vs (r = -0.528, -0.337, and 0.481, respectively, P < 0.05). The D fast values in the F4 group were significantly lower than those in the F0, F1 and F2 groups. D fast exhibited a non-inferior performance for diagnosing all fibrosis grades compared with that of Vs. CONCLUSIONS Both IVIM and ARFI provide reliable estimations for the noninvasive assessment of LF. KEY POINTS • Liver fibrosis can be diagnosed and graded using noninvasive imaging modalities. • ARFI and IVIM can be incorporated into routine examinations. • IVIM can differentiate liver cirrhosis from none to moderate liver fibrosis. • The diagnostic performances of IVIM and ARFI are equal.
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Affiliation(s)
- Chih-Horng Wu
- Department of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan.,Department of Radiology, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Ming-Chih Ho
- Department of Surgery, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.
| | - Yung-Ming Jeng
- Department of Pathology, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
| | - Po-Chin Liang
- Department of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan.,Department of Radiology, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Rey-Heng Hu
- Department of Surgery, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
| | - Hong-Shiee Lai
- Department of Surgery, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
| | - Tiffany Ting-Fang Shih
- Department of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan. .,Department of Radiology, National Taiwan University College of Medicine, Taipei, Taiwan.
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Ang SF, Ng ESH, Li H, Ong YH, Choo SP, Ngeow J, Toh HC, Lim KH, Yap HY, Tan CK, Ooi LLPJ, Chung AYF, Chow PKH, Foo KF, Tan MH, Cheow PC. The Singapore Liver Cancer Recurrence (SLICER) Score for relapse prediction in patients with surgically resected hepatocellular carcinoma. PLoS One 2015; 10:e0118658. [PMID: 25830231 PMCID: PMC4382157 DOI: 10.1371/journal.pone.0118658] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2014] [Accepted: 01/08/2015] [Indexed: 12/14/2022] Open
Abstract
Background and Aims Surgery is the primary curative option in patients with hepatocellular carcinoma (HCC). Current prognostic models for HCC are developed on datasets of primarily patients with advanced cancer, and may be less relevant to resectable HCC. We developed a postoperative nomogram, the Singapore Liver Cancer Recurrence (SLICER) Score, to predict outcomes of HCC patients who have undergone surgical resection. Methods Records for 544 consecutive patients undergoing first-line curative surgery for HCC in one institution from 1992–2007 were reviewed, with 405 local patients selected for analysis. Freedom from relapse (FFR) was the primary outcome measure. An outcome-blinded modeling strategy including clustering, data reduction and transformation was used. We compared the performance of SLICER in estimating FFR with other HCC prognostic models using concordance-indices and likelihood analysis. Results A nomogram predicting FFR was developed, incorporating non-neoplastic liver cirrhosis, multifocality, preoperative alpha-fetoprotein level, Child-Pugh score, vascular invasion, tumor size, surgical margin and symptoms at presentation. Our nomogram outperformed other HCC prognostic models in predicting FFR by means of log-likelihood ratio statistics with good calibration demonstrated at 3 and 5 years post-resection and a concordance index of 0.69. Using decision curve analysis, SLICER also demonstrated superior net benefit at higher threshold probabilities. Conclusion The SLICER score enables well-calibrated individualized predictions of relapse following curative HCC resection, and may represent a novel tool for biomarker research and individual counseling.
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Affiliation(s)
- Soo Fan Ang
- Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Republic of Singapore
- * E-mail: (MHT); (SFA)
| | - Elizabeth Shu-Hui Ng
- Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Republic of Singapore
| | - Huihua Li
- Health Services Research, Singapore General Hospital, Singapore, Republic of Singapore
- Centre for Quantitative Medicine, Duke-National University of Singapore Graduate Medical School, Singapore, Republic of Singapore
| | - Yu-Han Ong
- Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Republic of Singapore
| | - Su Pin Choo
- Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Republic of Singapore
| | - Joanne Ngeow
- Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Republic of Singapore
| | - Han Chong Toh
- Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Republic of Singapore
| | - Kiat Hon Lim
- Department of Pathology, Singapore General Hospital, Singapore, Republic of Singapore
| | - Hao Yun Yap
- Department of General Surgery, Singapore General Hospital, Singapore, Republic of Singapore
| | - Chee Kiat Tan
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore, Republic of Singapore
| | - London Lucien Peng Jin Ooi
- Department of Hepatobiliary and Transplant Surgery, Singapore General Hospital, Singapore, Republic of Singapore
| | - Alexander Yaw Fui Chung
- Department of Hepatobiliary and Transplant Surgery, Singapore General Hospital, Singapore, Republic of Singapore
| | - Pierce Kah Hoe Chow
- Division of Surgical Oncology, National Cancer Centre Singapore, Singapore, Republic of Singapore
- Office of Clinical Sciences, Duke-National University of Singapore Graduate Medical School, Singapore, Republic of Singapore
| | - Kian Fong Foo
- Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Republic of Singapore
| | - Min-Han Tan
- Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Republic of Singapore
- * E-mail: (MHT); (SFA)
| | - Peng Chung Cheow
- Department of Hepatobiliary and Transplant Surgery, Singapore General Hospital, Singapore, Republic of Singapore
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Kang TW, Kim JM, Rhim H, Lee MW, Kim YS, Lim HK, Choi D, Song KD, Kwon CHD, Joh JW, Paik SW, Paik YH, Ahn JH. Small Hepatocellular Carcinoma: Radiofrequency Ablation versus Nonanatomic Resection--Propensity Score Analyses of Long-term Outcomes. Radiology 2015; 275:908-19. [PMID: 25688888 DOI: 10.1148/radiol.15141483] [Citation(s) in RCA: 126] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
PURPOSE To compare radiofrequency (RF) ablation with nonanatomic resection (NAR) as first-line treatment in patients with a single Barcelona Clinic Liver Cancer (BCLC) stage 0 or A hepatocellular carcinoma (HCC) and to evaluate the long-term outcomes of both therapies. MATERIALS AND METHODS This retrospective study was approved by the institutional review board. The requirement for informed consent was waived. Data were reviewed from 580 patients with HCCs measuring 3 cm or smaller (BCLC stage 0 or A) who underwent ultrasonographically (US) guided percutaneous RF ablation (n = 438) or NAR (n = 142) as a first-line treatment. Local tumor progression, intrahepatic distant recurrence, disease-free survival, and overall survival rates were analyzed by using propensity score matching to compare therapeutic efficacy. In addition, major complications and length of postoperative hospital stay were compared. RESULTS Before propensity score matching (n = 580), the 5-year cumulative rates of local tumor progression for RF ablation and NAR (20.9% vs 12.7%, respectively; P = .093) and overall survival rates (85.5% vs 90.9%, respectively; P = .194) were comparable, while the 5-year cumulative intrahepatic distant recurrence rates (62.7% vs 36.6%, respectively; P < .001) and disease-free survival rates (31.7% vs 61.1%, respectively; P < .001) in the NAR group were significantly better than those in the RF ablation group. After matching (n = 198), there were no significant differences in therapeutic outcomes between the RF ablation and NAR groups, including 5-year cumulative intrahepatic distant recurrence (47.0% vs 40.2%, respectively; P = .240) and disease-free survival rates (48.9% vs 54.4%, respectively; P = .201). RF ablation was superior to NAR for major complication rates and length of postoperative hospital stay (P < .001). CONCLUSION In patients with one BCLC stage 0 or A (≤ 3 cm) HCC who received RF ablation or NAR as first-line treatment, there were no significant differences in long-term therapeutic outcomes; however, RF ablation was associated with fewer major complications and a shorter hospital stay after treatment.
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Affiliation(s)
- Tae Wook Kang
- From the Department of Radiology and Center for Imaging Science (T.W.K., H.R., M.W.L., Y.S.K., H.K.L., D.C., K.D.S.), Department of Surgery (J.M.K., C.H.D.K., J.W.J.), Division of Hepatology, Department of Medicine (S.W.P., Y.H.P.), and Biostatics Unit, Samsung Biomedical Research Institute (J.H.A.), Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-Dong, Gangnam-gu, Seoul 135-710, Korea
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Han DH, Choi GH, Park JY, Ahn SH, Kim KS, Choi JS, Han KH. Lesson from 610 liver resections of hepatocellular carcinoma in a single center over 10 years. World J Surg Oncol 2014; 12:192. [PMID: 24961934 PMCID: PMC4101710 DOI: 10.1186/1477-7819-12-192] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2014] [Accepted: 06/11/2014] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Recent advances in surgical techniques and perioperative management have led to improved surgical outcomes, especially perioperative outcomes. The aim of this study was to review our experience with hepatic resection for hepatocellular carcinoma (HCC) over a ten-year period to determine how to improve long-term surgical outcomes. METHODS From January 1996 to December 2007, 610 patients underwent curative resection for HCC at Yonsei University Health System, Seoul, Korea. Prognostic factors for disease-free and overall survival were identified, and surgical outcomes were compared between two time periods: before 2003 and after 2003. RESULTS The 1-, 3-, and 5-year overall survival rates were 90.1%, 74.9% and 64.4%, respectively. The patients after 2003 tended to have improved overall survival. The survival rate after recurrence in patients with tumors > 3 cm was significantly greater after 2003. (P = 0.044). CONCLUSIONS The improved survival rates after 2003 may be explained by better selection of surgical candidates, a reduced perioperative transfusion rate due to improved surgical techniques, and active multimodal treatment for recurrent HCC.
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Affiliation(s)
- Dai Hoon Han
- Department of Surgery, Yonsei University College of Medicine, 250 Seongsanno, Seodaemoon-gu, Seoul 120-752, Korea
- Yonsei Liver Cancer Special Clinic, Yonsei University College of Medicine, Seoul, Korea
| | - Gi Hong Choi
- Department of Surgery, Yonsei University College of Medicine, 250 Seongsanno, Seodaemoon-gu, Seoul 120-752, Korea
- Yonsei Liver Cancer Special Clinic, Yonsei University College of Medicine, Seoul, Korea
| | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Cancer Special Clinic, Yonsei University College of Medicine, Seoul, Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Cancer Special Clinic, Yonsei University College of Medicine, Seoul, Korea
| | - Kyung Sik Kim
- Department of Surgery, Yonsei University College of Medicine, 250 Seongsanno, Seodaemoon-gu, Seoul 120-752, Korea
- Yonsei Liver Cancer Special Clinic, Yonsei University College of Medicine, Seoul, Korea
| | - Jin Sub Choi
- Department of Surgery, Yonsei University College of Medicine, 250 Seongsanno, Seodaemoon-gu, Seoul 120-752, Korea
- Yonsei Liver Cancer Special Clinic, Yonsei University College of Medicine, Seoul, Korea
| | - Kwang-Hyub Han
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Cancer Special Clinic, Yonsei University College of Medicine, Seoul, Korea
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Zhou L, Rui JA, Wang SB, Chen SG, Qu Q. Clinicopathological Predictors of Poor Survival and Recurrence After Curative Resection in Hepatocellular Carcinoma Without Portal Vein Tumor Thrombosis. Pathol Oncol Res 2014; 21:131-8. [DOI: 10.1007/s12253-014-9798-2] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2013] [Accepted: 05/12/2014] [Indexed: 01/14/2023]
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Lee JI, Kim JK, Chang HY, Lee JW, Kim JM, Chung HJ, Kim YS, Lee KS. Impact of postoperative hepatitis B virus reactivation in hepatocellular carcinoma patients who formerly had naturally suppressed virus. J Gastroenterol Hepatol 2014; 29:1019-27. [PMID: 24325315 DOI: 10.1111/jgh.12472] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/27/2013] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIM Hepatitis B virus (HBV) replication detected before the resection of hepatocellular carcinoma (HCC) is to be controlled by antiviral agents. However, management strategy for patients with preoperatively undetectable HBV DNA without antiviral therapy is not clearly delineated. This study investigated viral reactivation after the liver resection in non-replicating HBV DNA-related HCC patients and its impact on the surgical outcome. METHODS From 198 patients that underwent liver resection due to HBV-related HCC, 101 patients who had serially checked serum HBV DNA were analyzed. RESULTS From 101 patients, 33 patients had baseline undetectable HBV DNA. Eleven patients (11/33, 33.3%) had viral replication after the liver resection. The postoperative viral reactivation (HR: 2.144; 95% CI: 1.122-4.097; P = 0.021), along with the existence of satellite nodules (HR: 3.034; 95% CI: 1.1.376-6.689; P = 0.006), existence of microvascular invasion (HR: 2.479; 95% CI: 1.303-4.718; P = 0.006), and HBeAg positivity (HR: 2.059; 95% CI: 1.155-3.670; P = 0.014) predicted recurrence after the surgery. Quantification of intrahepatic total and covalently closed circular DNA (cccDNA) was done in 14 patients whose baseline serum HBV DNA was undetectable without the use of antiviral agent. Amount of intrahepatic cccDNA expressed as copies/hepatocyte in patients with postoperative viral reactivation showed significantly higher than those in patients with sustained negative serum HBV DNA (P = 0.010). CONCLUSIONS This study shows that naturally suppressed preoperative HBV without application of antiviral agent does not ensure undetectable serum HBV after the surgery, and postoperative viral reactivation might be associated with HCC recurrence.
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Affiliation(s)
- Jung Il Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Liver Cirrhosis Clinical Trial Center, Seoul, Republic of Korea
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Li Z. Lymph node mapping in rabbit liver cancer with nanocarbon and methylene blue injecta. ASIAN PAC J TROP MED 2014; 6:400-3. [PMID: 23608381 DOI: 10.1016/s1995-7645(13)60046-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2013] [Revised: 04/15/2013] [Accepted: 05/01/2013] [Indexed: 12/22/2022] Open
Abstract
OBJECTIVE To discuss the value of lymph node mapping in rabbit liver cancer with nanocarbon and methylene blue injecta. METHODS Rabbit liver cancer model was established by transplanting VX2 cells with laparotomy in celiac planting method. Twenty Japan white rabbits were divided into two groups randomly. Each group had 10 rabbits. Lymph node mapping in two groups rabbit liver cancer were observed. Two groups rabbit liver cancer and local lymph nodes were removed. The number and location of local lymph nodes were recorded, and then the samples were obtained from both groups. RESULTS The lymph nodes dyed time was (100.50±29.92) s in nanocarbon group, and (11.20±4.18) s in methylene blue group with statistical significance between two groups (P=0.000). In the comparison of lymph node fading time, nanocarbon group was (2.22±0.74) h, methylene blue group was (1.63±0.54) h, nanocarbon group was longer than the methylene blue group, but without statistical significance (P=0.058). The accuracy was 87.5% (35/40) in methylene blue group, while, the nanocarbon group was 87.2% (34/39), with statistical significance (P=1.000). CONCLUSIONS Experimental results show that application of nanocarbon injection and methylene blue injection during resection of liver cancer and local lymph nodes in rabbit liver cancer model has obvious tracer function in liver cancer and lymphatic drainage. It can reduce the complexity and risk of the operation, and avoid the blindness in the process of traditional lymph node dissection surgery. Besides, they can effectively reduce the number of residual lymph nodes after operation. It can achieve the lymph node dissection more thoroughly, promptly, easily and safely.
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Affiliation(s)
- Zhong Li
- General Surgery Department, Affiliated Hospital of Armed Police Logistics College, Tianjin 300162, China.
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Detection of recurrent hepatocellular carcinoma on post-operative surveillance: comparison of MDCT and gadoxetic acid-enhanced MRI. ACTA ACUST UNITED AC 2014; 39:291-9. [DOI: 10.1007/s00261-013-0064-y] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
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Abul Seoud RA, Mabrouk MS. TMT-HCC: a tool for text mining the biomedical literature for hepatocellular carcinoma (HCC) biomarkers identification. COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE 2013; 112:640-648. [PMID: 23978553 DOI: 10.1016/j.cmpb.2013.07.014] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/01/2013] [Revised: 07/04/2013] [Accepted: 07/22/2013] [Indexed: 06/02/2023]
Abstract
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide. New insights into the pathogenesis of this lethal disease are urgently needed. Chromosomal copy number alterations (CNAs) can lead to activation of oncogenes and inactivation of tumor suppressors in human cancers. Thus, identification of cancer-specific CNAs will not only provide new insight into understanding the molecular basis of tumor genesis but also facilitate the identification of HCC biomarkers using CNA. This paper presents the TMT-HCC system; it is a tool for text mining the biomedical literature for hepatocellular carcinoma (HCC) biomarkers identification. TMT-HCC provides researchers with a powerful way to identify and discern molecular biomarkers of HCC to inform diagnosis, prognosis, and treatment driver genes with causal roles in carcinogenesis is to detect genomic regions that under frequent alterations in cancers (CNAs). TMT-HCC also extracts protein-protein interactions from the full text of the scientific papers. The results provided that the integration of genomic and transcriptional data offers powerful potential for identifying novel cancer genes in HCC pathogenesis.
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Affiliation(s)
- Rania A Abul Seoud
- Faculty of Engineering, Department of Electrical Engineering, Communication and Electronics Section, El Fayoum University, Fayoum 63514, Egypt.
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Hayashi T, Ohtsuka M, Okamura D, Seki N, Kimura F, Shimizu H, Yoshidome H, Kato A, Yoshitomi H, Furukawa K, Miyazaki M. Cytoskeleton-associated protein 2 is a potential predictive marker for risk of early and extensive recurrence of hepatocellular carcinoma after operative resection. Surgery 2013; 155:114-23. [PMID: 24238125 DOI: 10.1016/j.surg.2013.06.009] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2013] [Accepted: 06/20/2013] [Indexed: 01/22/2023]
Abstract
BACKGROUND De principe transplantation is an attractive strategy for the treatment of patients with hepatocellular carcinoma (HCC). The most important issue for this strategy is how to predict the risk of early and extensive recurrence. The present study aimed to identify a molecule associated with early and extensive recurrence of HCC after resection. METHODS Differentially expressed genes were screened by DNA microarray analysis with the use of 12 HCC samples from patients who had different clinical courses based on the timing and extent of recurrence after operative resection. Furthermore, the obtained results were validated in 60 independent samples by quantitative real-time reverse transcription-polymerase chain reaction. Immunohistochemistry was performed to assess gene expression at the protein level. RESULTS Microarray analysis and quantitative reverse transcription-polymerase chain reaction revealed cytoskeleton-associated protein 2 (CKAP2) as a candidate gene associated with early and extensive recurrence of HCC after resection. This observation was confirmed through examination of independent set samples, in which patients with greater-level CKAP2 mRNA expression exhibited shorter recurrence-free survival. Immunohistochemistry showed CKAP2 protein expression was associated with early (≤3 years) and extensive recurrence (beyond Milan criteria) after operative resection. CONCLUSION Immunohistochemical CKAP2 expression might be a potential biologic marker for identifying HCC patients at risk of early and extensive recurrence after operative resection.
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Affiliation(s)
- Tatsuya Hayashi
- Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Masayuki Ohtsuka
- Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
| | - Daiki Okamura
- Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Naohiko Seki
- Department of Functional Genomics, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Fumio Kimura
- Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Hiroaki Shimizu
- Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Hiroyuki Yoshidome
- Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Atsushi Kato
- Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Hideyuki Yoshitomi
- Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Katsunori Furukawa
- Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Masaru Miyazaki
- Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
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Faber W, Stockmann M, Schirmer C, Möllerarnd A, Denecke T, Bahra M, Klein F, Schott E, Neuhaus P, Seehofer D. Significant impact of patient age on outcome after liver resection for HCC in cirrhosis. Eur J Surg Oncol 2013; 40:208-13. [PMID: 24275202 DOI: 10.1016/j.ejso.2013.10.018] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2013] [Revised: 09/30/2013] [Accepted: 10/21/2013] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVE Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. The majority of patients with HCC have cirrhosis. Beside liver transplantation the resection is an established curative treatment option for patients with HCC in cirrhosis. However, the long term success is limited by a high tumor recurrence rate. Furthermore, by many patients surgical resection is restricted by poor liver function. The purpose of this study was to investigate the influence of patient age on long term outcome after liver resection in patients with HCC in cirrhotic liver. Further purpose was to define the potential prognostic factors. PATIENTS AND METHODS The outcome of 141 patients with liver cirrhosis after curative resection was analyzed using a prospective database. Only patients with postoperative histological assurance of HCC were included in the database. Patients with fibrolamellar HCC were excluded. RESULTS By patients below 70 years of age the 1-, 3- and 5-year survival rates were 78.5%, 56.5% and 47.1%. By patients over 70 years the 1-, 3- and 5-year survival rates were 59.9%, 40.3% and 6.7%. Cumulative survival of the total collective was significant influenced by patient age, Clavien grade, positive lymph vessels, mechanical ventilation and BMI. The overall postoperative morbidity was 44.7%. No intraoperative deaths were observed, but 11 patients (8 older than 70 and 3 younger than 70 years) died during the hospital stay. Clavien grade correlated with preoperative increased GGT, need for intraoperative blood and fresh frozen plasma transfusion. CONCLUSIONS Patient age and postoperative complications are more relevant for the outcome than many tumor factors, especially by patients over 70 years of age. In contrast, the prognosis of patients below 70 years of age is significantly better and a 5 year survival rate above 50% could be shown in our patients. However, by carefully selected elderly patients with HCC in cirrhosis an acceptable long term survival is reachable.
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Affiliation(s)
- W Faber
- Department of General, Visceral and Transplantation Surgery, Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany.
| | - M Stockmann
- Department of General, Visceral and Transplantation Surgery, Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany
| | - C Schirmer
- Department of General, Visceral and Transplantation Surgery, Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany
| | - A Möllerarnd
- Department of General, Visceral and Transplantation Surgery, Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany
| | - T Denecke
- Department of Radiology, Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany
| | - M Bahra
- Department of General, Visceral and Transplantation Surgery, Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany
| | - F Klein
- Department of General, Visceral and Transplantation Surgery, Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany
| | - E Schott
- Department of Gastroenterology and Hepatology, Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum, Germany
| | - P Neuhaus
- Department of General, Visceral and Transplantation Surgery, Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany
| | - D Seehofer
- Department of General, Visceral and Transplantation Surgery, Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany
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Chen Y, Huang A, Gao M, Yan Y, Zhang W. Potential therapeutic value of dendritic cells loaded with NY‑ESO‑1 protein for the immunotherapy of advanced hepatocellular carcinoma. Int J Mol Med 2013; 32:1366-72. [PMID: 24085111 DOI: 10.3892/ijmm.2013.1510] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2013] [Accepted: 09/17/2013] [Indexed: 12/25/2022] Open
Abstract
NY‑ESO‑1 is one of the most immunogenic cancer-testis (CT) antigens. Cancer vaccine trials based on NY‑ESO‑1 are currently ongoing. Dendritic cells (DCs) are the most potent antigen-presenting cells. The immune functions of DCs in a number of tumors have been identified; however, the potential therapeutic value of DCs pulsed with NY‑ESO‑1 in hepatocellular carcinoma (HCC) has not been extensively investigated. The objectives of the present study were to evaluate T cell response following stimulation with DCs pulsed with the recombinant NY‑ESO‑1 protein (rESO) and to establish a correlation between NY‑ESO‑1 expression and clinicopathological features in HCC patients. DCs were generated with granulocyte/macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL‑4) from human peripheral blood mononuclear cells. A mixed T cell reaction with DCs loaded with recombinant NY‑ESO‑1 protein (rESO-DCs) was evaluated by MTT assay. T cell responses against HCC cell lines were analyzed by measuring lactate dehydrogenase (LDH) activity. The protein levels of NY‑ESO‑1 were detected by immunohistochemistry (IHC) in a tissue microarray (TMA) containing 190 HCC samples. NY‑ESO‑1 transcript abundance was determined by reverse transcriptase-polymerase chain reaction (RT-PCR) in 54 out of the 190 HCC samples. The results revealed that mature DCs were induced and that rESO‑DCs significantly stimulated T cell proliferation. The specific lysis of T cells stimulated with rESO‑DCs was significantly higher in the NY‑ESO‑1-positive HCC cells compared with the NY‑ESO‑1-negative cells and the other controls (p<0.01). NY‑ESO‑1 was expressed in 15.8% (30/190)of the HCC samples, as shown by IHC and in 24.1% (13/54) of the samples, as shown by RT-PCR. The frequency of NY‑ESO‑1 expression was significantly higher in HCC patients with portal vein tumor thrombosis (24.6%) compared with those without thrombosis (11.2%, p=0.013). Our data suggest that DCs loaded with NY‑ESO‑1 protein stimulate antigen-specific T cell responses against HCC cells in vitro. NY‑ESO‑1 may thus be used as a potential target for immunotherapy in advanced HCC.
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Affiliation(s)
- Yuqing Chen
- Department of Pathology, Fujian Medical University, Fuzhou, Fujian 350004 P.R. China
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Abstract
Over 3 decades have passed since the first report of small hepatocellular carcinoma (SHCC), which has been confirmed as one of the most significant prognostic factors. Obviously, it is indeed very important to know when an early SHCC will become more aggressive and lead to worse clinical outcome once it grows beyond a critical size. However, so far, no consensus has been achieved on the size criterion for SHCC among different authors or different clinical practice guidelines that have been used worldwide, although there are currently numerous cutoff values for tumor size used to define SHCC, including 5, 3 and 2 cm in diameter, etc. Herein, based on our current understanding concerning the pathobiological features of SHCC, we briefly review the history of SHCC study, analyze the advantages and limitations of the above criteria for SHCC, and discuss the pathobiological characteristics as well as the clinical significance of SHCC.
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Affiliation(s)
- Wen-Ming Cong
- Department of Pathology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Changhai Road 225, Shanghai, 200438, China.
| | - Meng-Chao Wu
- Department of Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Changhai Road 225, Shanghai, 200438, China
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Mortality predicted accuracy for hepatocellular carcinoma patients with hepatic resection using artificial neural network. ScientificWorldJournal 2013; 2013:201976. [PMID: 23737707 PMCID: PMC3659648 DOI: 10.1155/2013/201976] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2013] [Accepted: 04/03/2013] [Indexed: 12/15/2022] Open
Abstract
The aim of this present study is firstly to compare significant predictors of mortality for hepatocellular carcinoma (HCC) patients undergoing resection between artificial neural network (ANN) and logistic regression (LR) models and secondly to evaluate the predictive accuracy of ANN and LR in different survival year estimation models. We constructed a prognostic model for 434 patients with 21 potential input variables by Cox regression model. Model performance was measured by numbers of significant predictors and predictive accuracy. The results indicated that ANN had double to triple numbers of significant predictors at 1-, 3-, and 5-year survival models as compared with LR models. Scores of accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC) of 1-, 3-, and 5-year survival estimation models using ANN were superior to those of LR in all the training sets and most of the validation sets. The study demonstrated that ANN not only had a great number of predictors of mortality variables but also provided accurate prediction, as compared with conventional methods. It is suggested that physicians consider using data mining methods as supplemental tools for clinical decision-making and prognostic evaluation.
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Giuliante F, Ardito F, Pinna AD, Sarno G, Giulini SM, Ercolani G, Portolani N, Torzilli G, Donadon M, Aldrighetti L, Pulitanò C, Guglielmi A, Ruzzenente A, Capussotti L, Ferrero A, Calise F, Scuderi V, Federico B, Nuzzo G. Liver resection for hepatocellular carcinoma ≤3 cm: results of an Italian multicenter study on 588 patients. J Am Coll Surg 2012; 215:244-54. [PMID: 22634119 DOI: 10.1016/j.jamcollsurg.2012.04.013] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2011] [Revised: 04/02/2012] [Accepted: 04/03/2012] [Indexed: 12/12/2022]
Abstract
BACKGROUND The best treatment for patients with small hepatocellular carcinoma (S-HCC) is still controversial. The aim of this study was to evaluate operative and long-term results after liver resection (LR) for S-HCC, defined as tumor ≤3 cm. STUDY DESIGN Retrospective multicenter study of 588 LRs for S-HCC from 8 Italian hepatobiliary surgery units (years 1992 to 2008). Primary outcomes included operative risk. Logistic regression analysis was used to evaluate risk factors for postoperative mortality. Secondary outcomes were overall survival (OS) and disease-free survival (DFS), estimated by the Kaplan-Meier method. RESULTS Postoperative mortality was 1.9%, morbidity was 35.7% (major morbidity 7.3%), and blood transfusion rate was 13.8%. Child-Pugh class B and blood transfusions were associated with higher postoperative mortality. Rates of microvascular invasion and microsatellite nodules were 37.0% and 23.1%. After a median follow-up of 38.4 months, 5- and 10-year OS rates were 52.8% and 20.3%, with DFS of 32.4% and 21.7%. Local recurrence rate was 1.4%. Between the years 2000 and 2008, 5-year OS was significantly higher than that between the years 1992 and 1999 (61.9% vs 42.6%; p < 0.001). In multivariable analysis, Child-Pugh class B, portal hypertension, and microsatellite lesions were independently associated with poor OS. Microsatellite lesion was the only variable independently associated with poor DFS. CONCLUSIONS Liver resection for S-HCC has improved over the years, with decreased operative risk. Long-term survival after LR has increased. Despite small tumor size, rates of microsatellite nodules and microvascular invasion are not negligible. Presence of microsatellite lesions was the only variable identified as being associated with poor both OS and DFS.
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Affiliation(s)
- Felice Giuliante
- Hepato-Biliary Surgery Unit, Department of Surgery, University Hospital Agostino Gemelli, Catholic University of the Sacred Heart, Rome, Italy.
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