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Galli E, Patelli G, Villa F, Gri N, Mazzarelli C, Mangoni I, Sgrazzutti C, Ghezzi S, Sartore-Bianchi A, Belli LS, De Carlis L, Vanzulli A, Siena S, Bencardino K. Circulating blood biomarkers for minimal residual disease in hepatocellular carcinoma: A systematic review. Cancer Treat Rev 2025; 135:102908. [PMID: 40058162 DOI: 10.1016/j.ctrv.2025.102908] [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: 11/09/2024] [Revised: 02/24/2025] [Accepted: 02/25/2025] [Indexed: 04/08/2025]
Abstract
BACKGROUND Relapse after radical treatment remains a major concern in hepatocellular carcinoma (HCC), affecting 50-75 % of early-stage cases within 5 years. Early recurrence prediction is a clinical unmet need. Circulating blood biomarkers could provide a minimally invasive approach to detect minimal residual disease (MRD) post-intervention. Although alpha-fetoprotein has been the primary biomarker in this setting, its MRD sensitivity is limited to 50-70 %. This systematic review aims to summarize available evidence regarding the clinical validity and potential utility of emerging circulating blood biomarkers for MRD detection in HCC patients. METHODS We searched PubMed and Embase for peer-reviewed articles and abstracts published up to 2025, and ClinicalTrials.gov for ongoing trials on circulating blood biomarkers for MRD in HCC. RESULTS A total of 91 studies (74 with results and 17 ongoing, out of 2,386) were retrieved. We evaluated various blood biomarkers, including circulating DNA (cDNA, N = 24), circulating tumor cells (CTCs, N = 20), circulating RNA (cRNA, N = 8), and other miscellaneous (N = 22) for MRD detection in HCC. These biomarkers demonstrated encouraging results, albeit with notable heterogeneity. In particular, circulating tumor DNA (ctDNA) and CTCs stand as the most robust novel approaches, with 50-80 % sensitivity and specificity up to 94 %. Nonetheless, none of the 17 ongoing studies involve biomarker-driven intervention to prove clinical utility. CONCLUSIONS Novel circulating blood biomarkers are mature for MRD detection in HCC. However, variability in methodologies and results highlights the need for further validation. We encourage the investigation of CTCs and/or ctDNA in interventional trials to assess clinical utility. This biomarker-driven approach may enhance adjuvant treatment effectiveness in MRD-positive cases while minimizing toxicity in MRD-negative patients.
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Affiliation(s)
- Edoardogregorio Galli
- Department of Oncology and Hemato-Oncology, Università degli Studi di Milano (La Statale), Milan, Italy; Niguarda Cancer Center, Department of Hematology, Oncology and Molecular Medicine, Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Giorgio Patelli
- Department of Oncology and Hemato-Oncology, Università degli Studi di Milano (La Statale), Milan, Italy; Niguarda Cancer Center, Department of Hematology, Oncology and Molecular Medicine, Grande Ospedale Metropolitano Niguarda, Milan, Italy; IFOM ETS - The AIRC Institute of Molecular Oncology, Milan, Italy.
| | - Federica Villa
- Niguarda Cancer Center, Department of Hematology, Oncology and Molecular Medicine, Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Nicole Gri
- Department of Oncology and Hemato-Oncology, Università degli Studi di Milano (La Statale), Milan, Italy; Niguarda Cancer Center, Department of Hematology, Oncology and Molecular Medicine, Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Chiara Mazzarelli
- Hepatology and Gastroenterology Unit, Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Iacopo Mangoni
- Department of General Surgery and Transplantation, Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | | | - Silvia Ghezzi
- Niguarda Cancer Center, Department of Hematology, Oncology and Molecular Medicine, Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Andrea Sartore-Bianchi
- Department of Oncology and Hemato-Oncology, Università degli Studi di Milano (La Statale), Milan, Italy; Niguarda Cancer Center, Department of Hematology, Oncology and Molecular Medicine, Grande Ospedale Metropolitano Niguarda, Milan, Italy; Division of Clinical Research and Innovation, Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Luca Saverio Belli
- Hepatology and Gastroenterology Unit, Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Luciano De Carlis
- Department of General Surgery and Transplantation, Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Angelo Vanzulli
- Department of Oncology and Hemato-Oncology, Università degli Studi di Milano (La Statale), Milan, Italy; Department of Radiology, Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Salvatore Siena
- Department of Oncology and Hemato-Oncology, Università degli Studi di Milano (La Statale), Milan, Italy; Niguarda Cancer Center, Department of Hematology, Oncology and Molecular Medicine, Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Katia Bencardino
- Niguarda Cancer Center, Department of Hematology, Oncology and Molecular Medicine, Grande Ospedale Metropolitano Niguarda, Milan, Italy
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Yang C, Wang H, Liu J, Yang F, Lv L, Jiang Y, Cai Q. Pre- to postoperative alpha-fetoprotein ratio-based nomogram to predict tumor recurrence in patients with hepatocellular carcinoma. Front Oncol 2023; 13:1134933. [PMID: 37124520 PMCID: PMC10140353 DOI: 10.3389/fonc.2023.1134933] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Accepted: 03/20/2023] [Indexed: 05/02/2023] Open
Abstract
Background This study aimed to investigate the role of the alpha fetoprotein (AFP) ratio before and after curative resection in the prognosis of patients with hepatocellular carcinoma (HCC) and to develop a novel pre- to postoperative AFP ratio nomogram to predict recurrence free survival (RFS) for HCC patients after curative resection. Methods A total of 485 pathologically confirmed HCC patients who underwent radical hepatectomy from January 2010 to December 2018 were retrospectively analyzed. The independent prognostic factors of hepatocellular carcinoma were identified by multivariate COX proportional model analysis, and the nomogram model was constructed. The receiver operating characteristic and the C-index were used to evaluate the accuracy and efficacy of the model prediction, the correction curve was used to assess the calibration of the prediction model, and decision curve analysis was used to evaluate the clinical application value of the nomogram model. Results A total of 485 HCC patients were divided into the training cohort (n = 340) and the validation cohort (n = 145) by random sampling at a ratio of 7:3. Using X-tile software, it was found that the optimal cut-off value of the AFP ratio in the training cohort was 0.8. In both cohorts, the relapse-free survival of patients with an AFP ratio <0.8 (high-risk group) was significantly shorter than in those with an AFP ratio ≥0.8 (low-risk group) (P < 0.05). An AFP ratio <0.8 was an independent risk factor for recurrence of HCC after curative resection. Based on the AFP ratio, BCLC stage and cirrhosis diagnosis, a satisfactory nomogram was developed. The AUC of our nomogram for predicting 1-, 3-, and 5-year RFS was 0.719, 0.690, and 0.708 in the training cohort and 0.721, 0.682, and 0.681 in the validation cohort, respectively. Furthermore, our model demonstrated excellent stratification as well as clinical applicability. Conclusion The AFP ratio was a reliable biomarker for tumor recurrence. This easy-to-use AFP ratio-based nomogram precisely predicted tumor recurrence in HCC patients after curative resection.
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Affiliation(s)
- Chengkai Yang
- The Fuzong Clinical Medical College of Fujian Medical University, Fuzhou, China
| | - Huaxiang Wang
- The Fuzong Clinical Medical College of Fujian Medical University, Fuzhou, China
- Department of Hepatobiliary and Pancreatic Surgery, Taihe Hospital, Affiliated Hospital of Hubei University of Medicine, Shiyan, China
| | - Jianyong Liu
- Department of Hepatobiliary Surgery, 900 Hospital of The Joint Logistics Team, Fuzhou, China
| | - Fang Yang
- Department of Hepatobiliary Surgery, 900 Hospital of The Joint Logistics Team, Fuzhou, China
| | - Lizhi Lv
- Department of Hepatobiliary Surgery, 900 Hospital of The Joint Logistics Team, Fuzhou, China
| | - Yi Jiang
- Department of Hepatobiliary Surgery, 900 Hospital of The Joint Logistics Team, Fuzhou, China
- *Correspondence: Qiucheng Cai, ; Yi Jiang,
| | - Qiucheng Cai
- Department of Hepatobiliary Surgery, 900 Hospital of The Joint Logistics Team, Fuzhou, China
- *Correspondence: Qiucheng Cai, ; Yi Jiang,
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Xu M, Xu D, Deng Z, Tian G, Jiang T. Long-term outcomes of endoscopic ultrasound-guided laser ablation for liver tumors in the caudate lobe: 5 years of experience. Scand J Gastroenterol 2022; 58:558-564. [PMID: 36415178 DOI: 10.1080/00365521.2022.2148833] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
OBJECTIVES Liver tumor in the caudate lobe is challenging to treat, partly due to its deep location. Endoscopic ultrasound-guided laser ablation (EUS-LA) is a new attractive option for tumors in high-risk or difficult-to-reach locations. This prospective study investigated the long-term efficacy of EUS-LA for tumors in the caudate lobe, and factors that predict outcomes. METHODS From June 2016 to July 2021, twenty consecutive patients (aged 56.95 ± 10.06 years) with 25 caudate lobe tumors (15.64 ± 6.37 mm) underwent EUS-LA. Treatment outcomes were assessed and predictive factors were calculated via univariate and multivariate analyses. RESULTS Twenty-five tumors achieved complete ablation after the first or second session of EUS-LA. The treatment effectiveness was 100%. During a median follow up of 27 months (3-60), four tumors (16%) developed local tumor progression and 15 patients (75%) experienced intrahepatic distant recurrence. According to univariate and multivariate analyses, the significant prognostic factor of local tumor progression was tumor size >2 cm (p = 0.047). Significant prognostic factors of intrahepatic distant recurrence were: tumor number, alpha-fetoprotein level, and total bilirubin level (p = 0.020, 0.019, 0.010, respectively). No adverse events related to EUS-LA were observed. CONCLUSION EUS-LA is a viable, safe, and effective treatment option for patients with liver tumor in the caudate lobe. Tumor size >2 cm increases the risk of post-procedural local tumor progression. Intrahepatic tumor number, and pretreatment alpha-fetoprotein level and total bilirubin level are associated with intrahepatic distant recurrence. REGISTRATION Clinicaltrials.gov, ID: NCT02816944(June 29, 2016).
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Affiliation(s)
- Min Xu
- Department of Ultrasound Medicine, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Danxia Xu
- Department of Ultrasound Medicine, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Zhuang Deng
- Department of Ultrasound Medicine, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Guo Tian
- Department of Ultrasound Medicine, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Tian'an Jiang
- Department of Ultrasound Medicine, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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Luo B, Liu L, Bi J, Bao S, Zhang Y. Role of the pre- to postoperative alpha-fetoprotein ratio in the prognostic evaluation of liver cancer after radiofrequency ablation. Int J Biol Markers 2022; 37:306-313. [PMID: 35686334 DOI: 10.1177/03936155221101075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
OBJECTIVE This study aimed to investigate the role of the alpha fetoprotein (AFP) ratio before and after radiofrequency ablation (RFA) in the prognosis of patients with liver cancer. METHODS A total of 368 patients who underwent RFA for liver cancer in Shenzhen People's Hospital from 2010 to 2020 were randomly divided into the training group and the validation group. Levels of AFP before and after RFA were recorded and their ratios were calculated. RESULTS Using the X-tile software, it was found that the optimal cut-off value of the AFP ratio in the training group was 37.9. Both in the training group and the validation group, the relapse-free survival and overall survival of patients with an AFP ratio <37.9 (high-risk group) were significantly shorter than those with an AFP ratio >37.9 (low-risk group) (training group, relapse-free survival, P = 0.0003; overall survival, P = 0.0186; validation group, relapse-free survival, P = 0.0490, overall survival, P = 0.0031). An AFP ratio <37.9 was an independent risk factor for recurrence and survival of liver cancer after RFA. CONCLUSION The AFP ratio can predict the prognosis of patients with liver cancer after RFA. An AFP ratio <37.9 is an independent risk factor for tumor recurrence and survival after RFA.
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Affiliation(s)
- Biwei Luo
- Department of Hepatobiliary and Pancreas Surgery, ShenZhen People's Hospital(The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), ShenZhen, GuangDong, China.,Department of General Surgery, ShenZhen People's Hospital, ShenZhen, GuangDong, China
| | - Linsen Liu
- Department of Hepatobiliary and Pancreas Surgery, ShenZhen People's Hospital(The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), ShenZhen, GuangDong, China.,Department of General Surgery, ShenZhen People's Hospital, ShenZhen, GuangDong, China
| | - Jian'gang Bi
- Department of Hepatobiliary and Pancreas Surgery, ShenZhen People's Hospital(The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), ShenZhen, GuangDong, China.,Department of General Surgery, ShenZhen People's Hospital, ShenZhen, GuangDong, China
| | - Shiyun Bao
- Department of Hepatobiliary and Pancreas Surgery, ShenZhen People's Hospital(The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), ShenZhen, GuangDong, China.,Department of General Surgery, ShenZhen People's Hospital, ShenZhen, GuangDong, China
| | - Yusen Zhang
- Department of Hepatobiliary and Pancreas Surgery, ShenZhen People's Hospital(The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), ShenZhen, GuangDong, China.,Department of General Surgery, ShenZhen People's Hospital, ShenZhen, GuangDong, China
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Wu Y, Peng W, Shen J, Zhang X, Li C, Wen T. The impact of tumor burden at the initial hepatectomy on the recurrence-to-death survival after repeat surgical resection/radiofrequency ablation: a retrospective study. BMC Surg 2022; 22:193. [PMID: 35585534 PMCID: PMC9118788 DOI: 10.1186/s12893-022-01643-7] [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: 02/08/2022] [Accepted: 05/10/2022] [Indexed: 02/08/2023] Open
Abstract
Background Previous studies have reported the surgical resection (SR) and radiofrequency ablation (RFA) could achieve comparable recurrence-to-death survival (RTDS). However, the impact of primary tumor burden on RTDS of patients with recurrent hepatocellular carcinoma (HCC) following SR or RFA has not been clarified. Methods From January 2009 to March 2015, 171 patients who underwent initial hepatectomy and second curative treatments in West China Hospital were retrospectively analyzed. Survival analysis was performed by the Kaplan–Meier method. Risk factors were identified using the Cox proportional hazard model. Results At initial hepatectomy, 96 patients (56.1%) were diagnosed with HCC within the Milan criteria (MC), and 75 patients (43.9%) were HCC beyond the MC. The clinicopathological features and re-treatment methods of recurrent HCC were similar between patients with primary HCC within or beyond the MC. Patients with primary HCC within the MC had longer recurrence time (31.4 ± 24.2 months vs. 20.2 ± 16 months, P < 0.001). The 1- and 3- year RTDS within and beyond the MC group were 88.8%, 57.6% and 79.0%, 46.3%, respectively (P = 0.093). In multivariate analysis, the recurrence time, tumor size and AFP > 400 ng/mL at the time of recurrence were associated with RTDS. Conclusions The primary tumor burden had no impact on RTDS, but had an impact on recurrence time. The recurrence time had an impact on RTDS and might be a good index to reflect the biology of recurrent HCC.
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Affiliation(s)
- Youwei Wu
- Department of Liver Surgery & Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Wei Peng
- Department of Liver Surgery & Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Junyi Shen
- Department of Liver Surgery & Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Xiaoyun Zhang
- Department of Liver Surgery & Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Chuan Li
- Department of Liver Surgery & Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Tianfu Wen
- Department of Liver Surgery & Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
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Hong SK, Lee KW, Lee S, Hong SY, Suh S, Han ES, Choi Y, Yi NJ, Suh KS. Impact of tumor size on hepatectomy outcomes in hepatocellular carcinoma: a nationwide propensity score matching analysis. Ann Surg Treat Res 2022; 102:193-204. [PMID: 35475226 PMCID: PMC9010965 DOI: 10.4174/astr.2022.102.4.193] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Revised: 02/19/2022] [Accepted: 02/22/2022] [Indexed: 11/30/2022] Open
Abstract
Purpose The aim of this study was to compare surgical outcomes after liver resection for hepatocellular carcinoma (HCC) according to tumor size using a large, nationwide cancer registry-based cohort and propensity score matching. Methods From 2008 to 2015, a total of 12,139 patients were diagnosed with liver cancer and registered in the Korean Primary Liver Cancer Registry. Patients without distant metastasis who underwent hepatectomy as a primary treatment were selected. We performed 1:1 propensity score matching between the small (<5 cm), large (≥5 cm and <10 cm), and huge (≥10 cm) groups. Results Overall, 265 patients in the small and large groups were compared, and 64 patients each in the large and huge groups were compared. The overall and progression-free survival rates were significantly lower in the large group than in the small group (P < 0.001 and P < 0.001, respectively). Overall survival tended to be poorer in the huge group than in the large group (P = 0.051). The progression-free survival rate was significantly lower in the huge group than in the large group (P = 0.002). Conclusion Although primary liver resection can be considered even in patients with huge HCC, greater caution with careful screening for recurrence is needed.
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Affiliation(s)
- Suk Kyun Hong
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Kwang-Woong Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Sola Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Su young Hong
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Sanggyun Suh
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Eui Soo Han
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - YoungRok Choi
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Nam-Joon Yi
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Kyung-Suk Suh
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
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Sun LY, Cen WJ, Tang WT, Deng L, Wang F, Ji XM, Yang JJ, Zhang RJ, Zhang XH, Du ZM. Alpha-Fetoprotein Ratio Predicts Alpha-Fetoprotein Positive Hepatocellular Cancer Patient Prognosis after Hepatectomy. DISEASE MARKERS 2022; 2022:7640560. [PMID: 35059044 PMCID: PMC8766187 DOI: 10.1155/2022/7640560] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/09/2021] [Accepted: 12/22/2021] [Indexed: 11/21/2022]
Abstract
BACKGROUND This study was conducted to investigate the effect of alpha-fetoprotein (AFP) ratio on the prognosis of AFP-positive hepatocellular carcinoma (HCC) patients after hepatectomy. METHODS We retrospectively included 879 HCC patients with AFP-positive who underwent hepatectomy from February 2012 to October 2017 and randomly divided into training cohort and validation cohort. AFP ratio was equal to the AFP level within one week before hepatectomy to AFP level within 20-40 days after surgery. The end point of follow-up was disease-free survival (DFS) and overall survival (OS). RESULTS AFP ratio was not associated with clinical characteristics in training cohort and validation cohort. According to the X-tile software, the optimum cut-off point was 17.8 for AFP ratio. Significant differences between AFP ratio high and AFP ratio low were observed in DFS and OS in both cohort (p < 0.05). Kaplan-Meier curves and receiver-operating curves were showed that AFP ratio was better than AFP level preoperation in predicting the prognosis of AFP-positive HCC patients after hepatectomy. The multivariate analysis demonstrated that AFP ratio was a significant independent risk factor for both OS and DFS in HCC patients with AFP-positive. CONCLUSIONS AFP ratio might be a prognosis predictor for HCC patients with AFP-positive after hepatectomy.
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Affiliation(s)
- Li-Yue Sun
- Second Department of Oncology, Guangdong Second Provincial General Hospital, 466 Xingang-Zhong Road, Guangzhou, China
| | - Wen-Jian Cen
- State Key Laboratory of Oncology in South China, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
- Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Wen-Ting Tang
- State Key Laboratory of Oncology in South China, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
- Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Ling Deng
- State Key Laboratory of Oncology in South China, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
- Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Fang Wang
- State Key Laboratory of Oncology in South China, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
- Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Xiao-Meng Ji
- State Key Laboratory of Oncology in South China, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
- Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Jiao-Jiao Yang
- State Key Laboratory of Oncology in South China, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
- Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Ren-Jing Zhang
- State Key Laboratory of Oncology in South China, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
- Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Xu-Hui Zhang
- Second Department of Oncology, Guangdong Second Provincial General Hospital, 466 Xingang-Zhong Road, Guangzhou, China
| | - Zi-Ming Du
- State Key Laboratory of Oncology in South China, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
- Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou, China
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Boral B, Ballı HT, Sözütok S, Pehlivan UA, Aikimbaev K. Clinical and prognostic significance of CD14 (+) HLA-DR (-/low) myeloid-derived suppressor cells in patients with hepatocellular carcinoma received transarterial radioembolization with Yttrium-90. Scand J Immunol 2021; 95:e13132. [PMID: 34936119 DOI: 10.1111/sji.13132] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2021] [Revised: 11/21/2021] [Accepted: 12/15/2021] [Indexed: 01/07/2023]
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. For unresectable HCC, transarterial radioembolization (TARE) with Yttrium-90 is a widely used treatment. The aim of this study was to investigate whether monocytic myeloid-derived suppressor cells (M-MDSC) and CD39+ T cells can be non-invasive predictive biomarkers of radiological response and prognosis in patients with HCC treated with TARE. This study was conducted on 39 patients with HCC who were treated with TARE between August 2018 and December 2019 and the control group consisted of 23 healthy volunteers. CD4+, CD8+, CD39+ T cells, Natural killer (NK) cells, myeloid cells (MC) and M-MDSC parameters are examined in the course of TARE treatment with student t test and Kaplan-Meier method. There were statistically significant differences in M-MDSC, CD39+ T cells and MC values between healthy controls and HCC patients. A statistically significant difference was found in M-MDSC and CD4+ T cells values in the HCC patient group who responded to the treatment compared to those who did not. Survival analysis found that patients with lower frequencies (under 3.81%) of M-MDSC showed more prominent differences of overall survival (OS) compared to patients with all high groups. We found that M-MDSC in the peripheral blood might be a useful non-invasive biomarker to predict OS. We have shown for the first time that M-MDSC is correlated with treatment response in HCC patients treated with TARE. Additionally, we have found that the percentage of CD39+ T cells is high in HCC patients and these cells are positively correlated with M-MDSC.
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Affiliation(s)
- Barış Boral
- Department of Immunology, Adana Health Practice and Research Center, University of Health Sciences, Adana, Turkey
| | | | - Sinan Sözütok
- Department of Radiology, Çukurova University School of Medicine, Adana, Turkey
| | - Umur Anıl Pehlivan
- Department of Radiology, Çukurova University School of Medicine, Adana, Turkey
| | - Kairgeldy Aikimbaev
- Department of Radiology, Çukurova University School of Medicine, Adana, Turkey
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Wang Q, Liu B, Qiao W, Li J, Yuan C, Long J, Hu C, Zang C, Zheng J, Zhang Y. The Dynamic Changes of AFP From Baseline to Recurrence as an Excellent Prognostic Factor of Hepatocellular Carcinoma After Locoregional Therapy: A 5-Year Prospective Cohort Study. Front Oncol 2021; 11:756363. [PMID: 34976804 PMCID: PMC8716397 DOI: 10.3389/fonc.2021.756363] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2021] [Accepted: 11/22/2021] [Indexed: 11/24/2022] Open
Abstract
Background Although many studies have confirmed the prognostic value of preoperative alpha-fetoprotein (AFP) in patients with hepatocellular carcinoma (HCC), the association between AFP at baseline (b-AFP), subsequent AFP at relapse (r-AFP), and AFP alteration and overall survival in HCC patients receiving locoregional therapy has rarely been systematically elucidated. Patients and Methods A total of 583 subjects with newly diagnosis of virus-related HCC who were admitted to Beijing You ‘an Hospital, Capital Medical University from January 1, 2012 to December 31, 2016 were prospectively enrolled. The influence of b-AFP, subsequent r-AFP, and AFP alteration on relapse and post-recurrence survival were analyzed. Results By the end of follow-up, a total of 431 (73.9%) patients relapsed and 200 (34.3%) died. Patients with positive b-AFP had a 24% increased risk of recurrence compared with those who were negative. Patients with positive r-AFP had a 68% increased risk of death after relapse compared with those who were negative. The cumulative recurrence-death survival (RDS) rates for 1, 3, 5 years in patients with negative r-AFP were 85.6% (184/215), 70.2%(151/215), and 67.4%(145/215), while the corresponding rates were 75.1% (154/205), 51.2% (105/205), and 48.8% (100/205) in those with positive AFP (P<0.001). 35 (21.6%) of the 162 patients with negative b-AFP turned positive at the time of recurrence, and of this subset, only 12 (34.3%) survived. Of the 255 patients with positive b-AFP, 86 (33.7%) turned negative at the time of relapse, and of this subset, only 30 (34.9%) died. The 1-, 3-, and 5-year cumulative RDS rates were also compared among groups stratified by AFP at baseline and relapse. The present study found that patients with positive AFP at baseline and relapse, as well as those who were negative turned positive, had the shortest RDS and OS. Conclusions Not only AFP at baseline but also subsequent AFP at relapse can be used to predict a post-recurrence survival, which can help evaluate mortality risk stratification of patients after relapse.
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Affiliation(s)
- Qi Wang
- Research Center for Biomedical Resources, Beijing You’an Hospital, Capital Medical University, Beijing, China
| | - Biyu Liu
- Research Center for Biomedical Resources, Beijing You’an Hospital, Capital Medical University, Beijing, China
| | - Wenying Qiao
- Research Center for Biomedical Resources, Beijing You’an Hospital, Capital Medical University, Beijing, China
| | - Jianjun Li
- Interventional Therapy Center for Oncology, Beijing You’an Hospital, Capital Medical University, Beijing, China
| | - Chunwang Yuan
- Interventional Therapy Center for Oncology, Beijing You’an Hospital, Capital Medical University, Beijing, China
| | - Jiang Long
- Interventional Therapy Center for Oncology, Beijing You’an Hospital, Capital Medical University, Beijing, China
| | - Caixia Hu
- Interventional Therapy Center for Oncology, Beijing You’an Hospital, Capital Medical University, Beijing, China
| | - Chaoran Zang
- Research Center for Biomedical Resources, Beijing You’an Hospital, Capital Medical University, Beijing, China
| | - Jiasheng Zheng
- Interventional Therapy Center for Oncology, Beijing You’an Hospital, Capital Medical University, Beijing, China
- *Correspondence: Yonghong Zhang, ; Jiasheng Zheng,
| | - Yonghong Zhang
- Research Center for Biomedical Resources, Beijing You’an Hospital, Capital Medical University, Beijing, China
- Interventional Therapy Center for Oncology, Beijing You’an Hospital, Capital Medical University, Beijing, China
- *Correspondence: Yonghong Zhang, ; Jiasheng Zheng,
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10
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Tipaldi MA, Ronconi E, Lucertini E, Krokidis M, Zerunian M, Polidori T, Begini P, Marignani M, Mazzuca F, Caruso D, Rossi M, Laghi A. Hepatocellular Carcinoma Drug-Eluting Bead Transarterial Chemoembolization (DEB-TACE): Outcome Analysis Using a Model Based On Pre-Treatment CT Texture Features. Diagnostics (Basel) 2021; 11:diagnostics11060956. [PMID: 34073545 PMCID: PMC8226518 DOI: 10.3390/diagnostics11060956] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 05/22/2021] [Accepted: 05/24/2021] [Indexed: 02/08/2023] Open
Abstract
(1) Introduction and Aim: The aim of this study is to investigate the prognostic value, in terms of response and survival, of CT-based radiomics features for patients with HCC undergoing drug-eluting beads transarterial chemoembolization (DEB-TACE). (2) Materials and Methods: Pre-treatment CT examinations of 50 patients with HCC, treated with DEB-TACE were manually segmented to obtain the tumor volumetric region of interest, extracting radiomics features with TexRAD. Response to therapy evaluation was performed basing on post-procedural CT examination compared to pre-procedural CT, using modified RECIST criteria for HCC. The prognostic value of texture analysis was evaluated, investigating the correlation between radiomics features, response to therapy and overall survival. Three models based on texture and clinical variables and a combination of them were finally built; (3) Results: Entropy, skewness, MPP and kurtosis showed a significant correlation with complete response (CR) to TACE (all p < 0.001). A predictive model to identify patients with a high and low probability of CR was evaluated with an ROC curve, with an AUC of 0.733 (p < 0.001). The three models built for survival prediction yielded an HR of 2.19 (95% CI: 2.03-2.35) using texture features, of 1.7 (95% CI: 1.54-1.9) using clinical data and of 4.61 (95% CI: 4.24-5.01) combining both radiomics and clinical data (all p < 0.0001). (4) Conclusion: Texture analysis based on pre-treatment CT examination is associated with response to therapy and survival in patients with HCC undergoing DEB-TACE, especially if combined with clinical data.
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Affiliation(s)
- Marcello Andrea Tipaldi
- Department of Surgical and Medical Sciences and Translational Medicine, Sapienza-University of Rome, 00189 Rome, Italy; (M.Z.); (M.R.); (A.L.)
- Department of Radiology, Sant’Andrea University of Hospital La Sapienza, 00189 Rome, Italy; (E.R.); (E.L.); (T.P.)
- Correspondence: ; Tel.: +39-06-33775391 (ext. 5893)
| | - Edoardo Ronconi
- Department of Radiology, Sant’Andrea University of Hospital La Sapienza, 00189 Rome, Italy; (E.R.); (E.L.); (T.P.)
| | - Elena Lucertini
- Department of Radiology, Sant’Andrea University of Hospital La Sapienza, 00189 Rome, Italy; (E.R.); (E.L.); (T.P.)
| | - Miltiadis Krokidis
- Department of Radiology, Areteion Hospital, National and Kapodistrian University of Athens, 11528 Athens, Greece;
- Department of Diagnostic, Interventional and Pediatric Radiology, Inselspital Bern University Hospital, University of Bern, 3010 Bern, Switzerland
| | - Marta Zerunian
- Department of Surgical and Medical Sciences and Translational Medicine, Sapienza-University of Rome, 00189 Rome, Italy; (M.Z.); (M.R.); (A.L.)
| | - Tiziano Polidori
- Department of Radiology, Sant’Andrea University of Hospital La Sapienza, 00189 Rome, Italy; (E.R.); (E.L.); (T.P.)
| | - Paola Begini
- Department of Liver Diseases Section, AOU Sant’Andrea Hospital, University of Hospital La Sapienza, 00189 Rome, Italy; (P.B.); (M.M.)
| | - Massimo Marignani
- Department of Liver Diseases Section, AOU Sant’Andrea Hospital, University of Hospital La Sapienza, 00189 Rome, Italy; (P.B.); (M.M.)
| | - Federica Mazzuca
- Department of Clinical and Molecular Oncology-Sapienza, University of Rome, Sant’Andrea University Hospital, via di Grottarossa 1035, 00189 Rome, Italy;
| | - Damiano Caruso
- Department of Radiological Sciences, Oncological and Pathological Sciences, University of Rome Sapienza, Sant’Andrea University Hospital, 00189 Rome, Italy;
| | - Michele Rossi
- Department of Surgical and Medical Sciences and Translational Medicine, Sapienza-University of Rome, 00189 Rome, Italy; (M.Z.); (M.R.); (A.L.)
- Department of Radiology, Sant’Andrea University of Hospital La Sapienza, 00189 Rome, Italy; (E.R.); (E.L.); (T.P.)
| | - Andrea Laghi
- Department of Surgical and Medical Sciences and Translational Medicine, Sapienza-University of Rome, 00189 Rome, Italy; (M.Z.); (M.R.); (A.L.)
- Department of Radiology, Sant’Andrea University of Hospital La Sapienza, 00189 Rome, Italy; (E.R.); (E.L.); (T.P.)
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11
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Bhatti ABH, Sheikh AAE, Mahmud US, Zeeshan S, Khan NY, Zia HH, Dar FS, Rana A. Clinical Profile and Treatment of Hepatocellular Carcinoma: A Single-Center Experience. South Asian J Cancer 2021; 10:76-80. [PMID: 34568219 PMCID: PMC8460341 DOI: 10.1055/s-0041-1729451] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Background Very few centers in Pakistan have all established treatments for hepatocellular carcinoma (HCC) available under one roof. With a dedicated hepato-pancreato-biliary surgery and liver transplant unit, we have gathered one of the largest data on HCC in our population. Aims The objective of the current study was to assess the clinical spectrum of HCC in Pakistani patients. Settings and Design This retrospective review of patients diagnosed with HCC was conducted between 2011 and 2016. Materials and Methods Patients were allocated to treatment groups based on the Barcelona clinic liver cancer (BCLC) staging algorithm and our local guidelines. The treatment options were grouped as curative (radiofrequency ablation [RFA], percutaneous ethanol injection [PEI], liver resection, and liver transplantation), palliative (transarterial chemoembolization [TACE]/sorafenib), and the best supportive care (BSC). Statistical Analysis Kaplan-Meier curves were used for the statistical analysis. Results The mean age was 57.9 ± 10.1 years (range: 18-90 years). The male-to-female ratio was (1,099/391) 2.8:1. Hepatitis B and hepatitis C were the most common underlying etiological factor in 1,350 of 1,490 (90.6%) patients. Macrovascular invasion (MVI) was seen in 492 of 1,490 (33%) patients. Out of the total, 191 (12.8%) additional patients were offered potentially curative treatments when compared with BCLC recommendations. The actuarial 5-year overall survival for patients who underwent liver transplant, RFA/PEI, TACE, sorafenib, and BSC was 87, 64, 18, 5, and 0%, respectively. Alpha fetoprotein cut-off of 400 ng/mL had a significant impact on survival irrespective of treatment received (41 vs. 11%, p < 0.0001). Conclusion MVI is the most frequent poor prognostic marker in our patients with HCC. Local treatment guidelines are effective in yielding comparable outcomes to BCLC.
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Affiliation(s)
- Abu B. H. Bhatti
- Department of Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Shifa International Hospital, Islamabad, Pakistan
| | - Abdul A. E. Sheikh
- Department of Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Shifa International Hospital, Islamabad, Pakistan
| | - Umair S. Mahmud
- Department of Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Shifa International Hospital, Islamabad, Pakistan
| | - Shagufta Zeeshan
- Department of Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Shifa International Hospital, Islamabad, Pakistan
| | - Nusrat Y. Khan
- Department of Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Shifa International Hospital, Islamabad, Pakistan
| | - Haseeb H. Zia
- Department of Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Shifa International Hospital, Islamabad, Pakistan
| | - Faisal S. Dar
- Department of Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Shifa International Hospital, Islamabad, Pakistan
| | - Atif Rana
- Department of Radiology, Shifa International Hospital, Islamabad, Pakistan
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12
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Chen HL, Chen YH, Du L, Song YP, Zhu B. Elevated serum alpha-fetoprotein levels are associated with poor prognosis of hepatocellular carcinoma after surgical resection: A systematic review and meta-analysis. Arab J Gastroenterol 2021; 22:12-22. [PMID: 33551350 DOI: 10.1016/j.ajg.2020.09.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2019] [Revised: 06/22/2020] [Accepted: 09/08/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND STUDY AIMS The relationship between the alpha-fetoprotein (AFP) level and the prognosis of hepatocellular carcinoma (HCC) after surgical resection remains unknown. This study aims to assess this relationship. PATIENTS AND METHODS PubMed and Web of Science were systematically utilised. Meta-analysis was conducted for the outcomes of the recurrence-free survival (RFS) and the overall survival (OS) by comparing the high AFP group with the low AFP group. RESULTS The studies included 61 manuscripts with 35,461 patients. The summary hazard ratio (HR) for RFS was 1.501 (95% CI 1.355-1.662; Z = 7.81, P < 0.00001) when comparing the high AFP group with the low AFP group. Sensitivity analysis only included adjusted HRs, with the summary HR being 1.563 (95% CI 1.381-1.768; Z = 7.10, P < 0.00001). The summary HR for OS was 1.565 (95% CI 1.439-1.701; Z = 10.52, P < 0.00001) when comparing two AFP groups. Sensitivity analysis showed that the summary HR was 1.611 (95% CI 1.456-1.782; Z = 9.24, P < 0.00001). CONCLUSION Our meta-analysis indicated that elevated serum AFP levels are associated with poor prognosis of HCC after surgical resection.
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Affiliation(s)
- Hong-Lin Chen
- Nantong University, School of Public Health, Nantong City, Jiangsu Province, China
| | - Yu-Hua Chen
- Nantong Health College of Jiangsu Province, Nantong City, Jiangsu Province, China
| | - Lin Du
- Nantong University, School of Public Health, Nantong City, Jiangsu Province, China
| | - Yi-Ping Song
- Nantong University, School of Public Health, Nantong City, Jiangsu Province, China
| | - Bin Zhu
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Nantong University, China.
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13
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Muscari F, Maulat C. Preoperative alpha-fetoprotein (AFP) in hepatocellular carcinoma (HCC): is this 50-year biomarker still up-to-date? Transl Gastroenterol Hepatol 2020; 5:46. [PMID: 33073041 DOI: 10.21037/tgh.2019.12.09] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2019] [Accepted: 12/12/2019] [Indexed: 12/12/2022] Open
Affiliation(s)
- Fabrice Muscari
- Department of Digestive Surgery and Transplantation, Toulouse University Hospital, Toulouse, France
| | - Charlotte Maulat
- Department of Digestive Surgery and Transplantation, Toulouse University Hospital, Toulouse, France
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14
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LncRNA KCNQ1OT1 regulates the invasion and migration of hepatocellular carcinoma by acting on S1PR1 through miR-149. Cancer Gene Ther 2020; 28:850-863. [PMID: 32753631 DOI: 10.1038/s41417-020-0203-x] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Revised: 07/07/2020] [Accepted: 07/22/2020] [Indexed: 02/06/2023]
Abstract
The aim of this study was to investigate the effect of lncRNA KCNQ1OT1 on HCC and to explore the possible underlying mechanisms. The expression levels of KCNQ1OT1, miR-149 and S1PR1 were detected by qRT-PCR assay. A dual luciferase reporter assay was used to detect the interaction between KCNQ1OT1 and miR-149, as well as miR-149 and S1PR1. The interaction between KCNQ1OT1 and miR-149 was further investigated by RNA pull-down assay. Wound healing assays and Transwell assays were carried out to determine cell migration and invasion. A xenograft tumour assay was used to validate the role of KCNQ1OT1 in vivo. KCNQ1OT1 and S1PR1 were significantly increased, but miR-149 was decreased in HCC cells. Luciferase reporter assays and RNA pull-down assays revealed that KCNQ1OT1 directly targeted miR-149. In addition, miR-149 bound to the 3'-UTR of S1PR1. Knockdown of KCNQ1OT1 or overexpression of miR-149 inhibited the invasion and migration of HCC cells. However, suppression of miR-149 could abrogate the effect of KCNQ1OT1 knockdown on the invasion and migration abilities of HCC cells. In vivo assays showed that KCNQ1OT1 knockdown suppressed tumour growth. This work suggests that lncRNA KCNQ1OT1 might act as a potential therapeutic target in HCC.
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15
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Liu W, Xu H, Ying X, Zhang D, Lai L, Wang L, Tu J, Ji J. Radiofrequency Ablation (RFA) Combined with Transcatheter Arterial Chemoembolization (TACE) for Patients with Medium-to-Large Hepatocellular Carcinoma: A Retrospective Analysis of Long-Term Outcome. Med Sci Monit 2020; 26:e923263. [PMID: 32667906 PMCID: PMC7382301 DOI: 10.12659/msm.923263] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND The aim of this study was to investigate the prognostic value of radiofrequency ablation (RFA) plus transcatheter arterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) patients with tumor size ranging from 3.0 to 10.0 cm. MATERIAL AND METHODS We retrospectively analyzed data on 201 patients with medium-to-large HCC. According to treatment procedure, the patients were divided into the TACE group (n=124) and the TACE+RFA group (n=77). We recorded data on patient safety, subcapsular hepatic hematoma, large amount of ascites, liver abscess, gallbladder injury, and local skin infection. The overall survival (OS) and progression-free survival (PFS) in the 2 groups were analyzed and compared between groups. RESULTS The median PFS was 4.00 months (3.00-5.00 months) in the TACE group and 9.13 months (6.64-11.62 months) in the TACE+RFA group (P<0.001). Median OS was 12.00 months (8.88-15.13 months) in the TACE group and 27.57 months (20.06-35.08 months) in the TACE+RFA group (P<0.001). In the TACE+RFA group, multivariate Cox regression analysis showed that tumor size ≤5 cm) (HR: 1.952, 95% CI: 1.213-3.143, P=0.006), hepatitis B (HR: 2.323, 95% CI: 1.096-4.923, P=0.028), TACE times (1 or >1) (HR: 1.867, 95% CI: 1.156-3.013, P=0.011), alpha-fetoprotein (AFP) level >200 ng/ml (HR: 2.426, 95% CI: 1.533-3.839, P<0.001), and AST level >40 U/L (HR: 1.946, 95% CI: 1.196-3.166, P=0.007) were independent prognostic factors for overall survival. CONCLUSIONS Combination therapy of TACE with RFA is a safe and effective treatment for patients with medium-to-large HCC, with the long-term beneficial effect of retarding tumor progression and improving PFS and OS.
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Affiliation(s)
- Weiwen Liu
- Department of Radiology, Lishui Central Hospital/Key Laboratory of Imaging Diagnosis and Minimally Invasive Interventional Research of Zhejiang, Lishui, Zhejiang, China (mainland)
| | - Huihong Xu
- Department of Radiology, Qingtian County People's Hospital of Lishui City, Lishui, Zhejiang, China (mainland)
| | - Xihui Ying
- Department of Radiology, Lishui Central Hospital/Key Laboratory of Imaging Diagnosis and Minimally Invasive Interventional Research of Zhejiang, Lishui, Zhejiang, China (mainland)
| | - Dengke Zhang
- Department of Radiology, Lishui Central Hospital/Key Laboratory of Imaging Diagnosis and Minimally Invasive Interventional Research of Zhejiang, Lishui, Zhejiang, China (mainland)
| | - Linqiang Lai
- Department of Radiology, Lishui Central Hospital/Key Laboratory of Imaging Diagnosis and Minimally Invasive Interventional Research of Zhejiang, Lishui, Zhejiang, China (mainland)
| | - Linyou Wang
- Department of Radiology, Taizhou Municipal Hospital of Zhejiang Province, Taizhou, Zhejiang, China (mainland)
| | - Jianfei Tu
- Department of Radiology, Lishui Central Hospital/Key Laboratory of Imaging Diagnosis and Minimally Invasive Interventional Research of Zhejiang, Lishui, Zhejiang, China (mainland)
| | - Jiansong Ji
- Department of Radiology, Lishui Central Hospital/Key Laboratory of Imaging Diagnosis and Minimally Invasive Interventional Research of Zhejiang, Lishui, Zhejiang, China (mainland)
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16
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Ince V, Carr BI, Bag HG, Koc C, Usta S, Ersan V, Baskiran A, Sahin TT, Yilmaz S. Gamma glutamyl transpeptidase as a prognostic biomarker in hepatocellular cancer patients especially with >5 cm tumors, treated by liver transplantation. Int J Biol Markers 2020; 35:91-95. [PMID: 32436751 DOI: 10.1177/1724600820921869] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Serum AFP levels are typically elevated in less than 50% of hepatocellular cancer (HCC) patients. Gamma-glutamyl transpeptidase (GGT) levels have been suggested to be a potentially useful HCC biomarker. AIMS To assess in a cohort of prospectively evaluated HCC patients who underwent liver transplant and whose survival was known; the occurrence, prognosis, and clinical characteristics of patients with elevated serum GGT levels. RESULTS Serum GGT levels were found to be elevated in a higher proportion in patients with either small or large HCC than alpha-fetoprotein (AFP) levels, and were significantly related to prognosis in patients with large size HCCs. There was no clear correlation between GGT and AFP levels, likely reflecting different HCC characteristics or HCC cell lineages associated with these two markers. Furthermore, elevated GGT was found in 24% of low-AFP patients with small tumors and 46% with large tumors. Elevated GGT levels were also significantly associated with microvascular invasion and tumor diameter. CONCLUSIONS Elevated serum GGT levels were associated with HCC size and worse survival, and were unrelated to AFP levels. GGT may be a useful prognostic tumor marker, especially for low-AFP HCC patients.
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Affiliation(s)
- Volkan Ince
- Department of Surgery, Liver Transplantation Institute, Inonu University, Malatya, Turkey
| | - Brian I Carr
- Department of Surgery, Liver Transplantation Institute, Inonu University, Malatya, Turkey
| | - Harika Gozukara Bag
- Department of Biostatistics, Medical School, Inonu University, Malatya, Turkey
| | - Cemalettin Koc
- Department of Surgery, Liver Transplantation Institute, Inonu University, Malatya, Turkey
| | - Sertac Usta
- Department of Surgery, Liver Transplantation Institute, Inonu University, Malatya, Turkey
| | - Veysel Ersan
- Department of Surgery, Liver Transplantation Institute, Inonu University, Malatya, Turkey
| | - Adil Baskiran
- Department of Surgery, Liver Transplantation Institute, Inonu University, Malatya, Turkey
| | - Tevfik Tolga Sahin
- Department of Surgery, Liver Transplantation Institute, Inonu University, Malatya, Turkey
| | - Sezai Yilmaz
- Department of Surgery, Liver Transplantation Institute, Inonu University, Malatya, Turkey
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17
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Mishra G, Dev A, Paul E, Cheung W, Koukounaras J, Jhamb A, Marginson B, Lim BG, Simkin P, Borsaru A, Burnes J, Goodwin M, Ramachandra V, Spanger M, Lubel J, Gow P, Sood S, Thompson A, Ryan M, Nicoll A, Bell S, Majeed A, Kemp W, Roberts SK. Prognostic role of alpha-fetoprotein in patients with hepatocellular carcinoma treated with repeat transarterial chemoembolisation. BMC Cancer 2020; 20:483. [PMID: 32471447 PMCID: PMC7257176 DOI: 10.1186/s12885-020-06806-4] [Citation(s) in RCA: 4] [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: 01/09/2020] [Accepted: 03/30/2020] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Repeat transarterial chemoembolisation (rTACE) is often required for hepatocellular carcinoma (HCC) to achieve disease control, however, current practice guidelines regarding treatment allocation vary significantly. This study aims to identify key factors associated with patient survival following rTACE to facilitate treatment allocation and prognostic discussion. METHOD Patients with HCC undergoing rTACE at six Australian tertiary centers from 2009 to 2014 were included. Variables encompassing clinical, tumour, treatment type and response factors were analysed against the primary outcome of overall survival. Univariate analysis and multivariate Cox regression modelling were used to identify factors pre- and post-TACE therapy significantly associated with survival. RESULTS Total of 292 consecutive patients underwent rTACE with mainly Child Pugh A cirrhosis (61%) and BCLC stage A (57%) disease. Median overall survival (OS) was 30 months (IQR 15.2-50.2) from initial TACE. On multivariate analysis greater tumour number (p = 0.02), higher serum bilirubin (p = 0.007) post initial TACE, and hepatic decompensation (p = 0.001) post second TACE were associated with reduced survival. Patients with serum AFP ≥ 200 ng/ml following initial TACE had lower survival (p = 0.001), compared to patients with serum AFP level that remained < 200 ng/ml post-initial TACE, with an overall survival of 19.4 months versus 34.7 months (p = 0.0001) respectively. CONCLUSION Serum AFP level following initial treatment in patients undergoing repeat TACE for HCC is a simple and useful clinical prognostic marker. Moreover, it has the potential to facilitate appropriate patient selection for rTACE particularly when used in conjunction with baseline tumour burden and severity of hepatic dysfunction post-initial TACE.
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Affiliation(s)
- Gauri Mishra
- Gastroenterology, Monash Health, Melbourne, Australia
| | - Anouk Dev
- Gastroenterology, Monash Health, Melbourne, Australia
| | - Eldho Paul
- School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
| | - Wa Cheung
- Radiology, Alfred Health, Melbourne, Australia
| | | | - Ashu Jhamb
- Radiology, St. Vincent's Hospital, Melbourne, Australia
| | - Ben Marginson
- Radiology, St. Vincent's Hospital, Melbourne, Australia
| | - Beng Ghee Lim
- Radiology, Royal Melbourne Hospital, Melbourne, Australia
| | - Paul Simkin
- Radiology, Royal Melbourne Hospital, Melbourne, Australia
| | - Adina Borsaru
- Radiology, Monash Health Eastern Health, Melbourne, Australia
| | - James Burnes
- Radiology, Monash Health Eastern Health, Melbourne, Australia
| | | | | | | | - John Lubel
- Department of Gastroenterology, The Alfred Hospital, 55 Commercial Rd, Melbourne, 3004, Australia
| | - Paul Gow
- Gastroenterology, Austin Health, Melbourne, Australia
| | - Siddharth Sood
- Gastroenterology, Royal Melbourne Hospital, Melbourne, Australia
| | | | - Marno Ryan
- Gastroenterology, St. Vincent's Hospital, Melbourne, Australia
| | - Amanda Nicoll
- Gastroenterology, Eastern Health, Melbourne, Australia
| | - Sally Bell
- Gastroenterology, Monash Health, Melbourne, Australia
| | - Ammar Majeed
- Department of Gastroenterology, The Alfred Hospital, 55 Commercial Rd, Melbourne, 3004, Australia
| | - William Kemp
- Department of Gastroenterology, The Alfred Hospital, 55 Commercial Rd, Melbourne, 3004, Australia
| | - Stuart K Roberts
- Department of Gastroenterology, The Alfred Hospital, 55 Commercial Rd, Melbourne, 3004, Australia.
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18
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α-Fetoprotein (AFP)-L3% and transforming growth factor B1 (TGFB1) in prognosis of hepatocellular carcinoma after radiofrequency. EGYPTIAN LIVER JOURNAL 2019. [DOI: 10.1186/s43066-019-0008-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Numerous hepatocellular carcinoma (HCC) biomarkers have been assessed in the diagnosis and prognosis of HCC. The aim of this study was to assess the value of α-fetoprotein (AFP)-L3% and transforming growth factor B1 (TGFB1) as prognostic markers in hepatocellular carcinoma after radiofrequency ablation (RFA). This observational cohort study included 40 patients with HCC diagnosed by triphasic computed tomography criteria indicated for radiofrequency ablation. Serum AFP, AFP-L3%, and TGFB1 were measured in all patients before and 3 months after radiofrequency ablation.
Results
Statistically significant lower levels of TGFB1, AFP, and AFP-L3% were noted in the HCC patients after radiofrequency ablation. Significant lower levels of TGFB1, AFP, and AFP-L3% were found in the no recurrence group in comparison to the recurrence group. The cutoff value of TGFB1 > 56.87 ng/mL, AFP > 74.9 ng/mL, and AFP-L3% > 8.5% was the best in the discrimination of tumor recurrence with sensitivity of 85.7%, 57.1%, and 100%; specificity of 54.6%, 84.9%, and 100%; and diagnostic accuracy of 64.5%, 69%, and 100%, respectively.
Conclusion
TGFB1 and AFP-L3% are good prognostic markers for HCC. They could be used to monitor the response of HCC to treatment.
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19
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Milan-out Criteria and Worse Intention-to-Treat Outcome Postliver Transplantation. Transplant Direct 2019; 5:e487. [PMID: 31723582 PMCID: PMC6791598 DOI: 10.1097/txd.0000000000000934] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2019] [Accepted: 07/23/2019] [Indexed: 12/13/2022] Open
Abstract
Milan criteria are widely used for liver transplantation selection in hepatocellular carcinoma but have been recognized to be too restrictive. Milan-out criteria are increasingly being adopted. Our aim was to analyze if liver transplantation waitlisted Milan-out hepatocellular carcinoma patients have different outcome than Milan patients.
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20
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Li XL, Zhu XD, Cai H, Li Y, Zhou J, Fan J, Tang ZY, Sun HC. Postoperative α-fetoprotein response predicts tumor recurrence and survival after hepatectomy for hepatocellular carcinoma: A propensity score matching analysis. Surgery 2019; 165:1161-1167. [PMID: 30846192 DOI: 10.1016/j.surg.2019.01.009] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2018] [Revised: 01/02/2019] [Accepted: 01/19/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND To investigate the prognostic values of the change of α-fetoprotein within 1 week after resection of hepatocellular carcinoma. METHODS We retrospectively analyzed patients with hepatocellular carcinoma who underwent curative hepatectomy as primary therapy at Zhongshan Hospital, Fudan University (Shanghai, China) from 2009 to 2011. We measured serum α-fetoprotein before (α-fetoprotein0) and 1 week after (α-fetoprotein7) hepatectomy, calculated change of α-fetoprotein, namely the α-fetoprotein response by the formula: AR = lgAFP7/lgAFP0 (lg = log10), analyzed the relationship between patient survival and α-fetoprotein response, and explored the potential clinical implications of the α-fetoprotein response. The results were validated in an independent cohort of patients from the same institute. RESULTS A total of 841 eligible patients were analyzed. We determined that the optimal cutoff value of the α-fetoprotein response was 0.8135 and subsequently classified patients from the exploration cohort into the α-fetoprotein responder (α-fetoprotein response ≤ 0.8135; n = 452) and α-fetoprotein nonresponder (α-fetoprotein response > 0.8135; n = 146). Multivariate Cox analysis showed that the α-fetoprotein response independently predicted overall survival (OS) and recurrence-free survival (RFS) time after resection (both P < .001). In patients with a higher risk of tumor recurrence (either single tumor with microvascular invasion or multiple tumors), α-fetoprotein responders were associated with better survival than the nonresponders (P < .05). The results were validated by propensity score matched population and another independent cohort. CONCLUSION The α-fetoprotein response is a reliable and simple predictive marker for evaluating the oncological effect of surgical resection for hepatocellular carcinoma with positive α-fetoprotein before resection, independent of tumor features.
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Affiliation(s)
- Xiao-Long Li
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China
| | - Xiao-Dong Zhu
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China
| | - Hao Cai
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China
| | - Yan Li
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China
| | - Jian Zhou
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China
| | - Jia Fan
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China
| | - Zhao-You Tang
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China
| | - Hui-Chuan Sun
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China.
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Down-regulation of siglec-2 (CD22) predicts worse overall survival from HBV-related early-stage hepatocellular carcinoma: a preliminary analysis from Gene Expression Omnibus. Biosci Rep 2018; 38:BSR20181423. [PMID: 30355653 PMCID: PMC6259014 DOI: 10.1042/bsr20181423] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2018] [Revised: 10/11/2018] [Accepted: 10/17/2018] [Indexed: 01/10/2023] Open
Abstract
Sialic-acid-binding immunoglobulin-like lectin (siglec) regulates cell death, anti-proliferative effects and mediates a variety of cellular activities. Little was known about the relationship between siglecs and hepatocellular carcinoma (HCC) prognosis. Siglec gene expression between tumor and non-tumor tissues were compared and correlated with overall survival (OS) from HCC patients in GSE14520 microarray expression profile. Siglec-1 to siglec-9 were all down-regulated in tumor tissues compared with those in non-tumor tissues in HCC patients (all P < 0.05). Univariate and multivariate Cox regression analysis revealed that siglec-2 overexpression could predict better OS (HR = 0.883, 95%CI = 0.806-0.966, P = 0.007). Patients with higher siglec-2 levels achieved longer OS months than those with lower siglec-2 levels in the Kaplan-Meier event analysis both in training and validation sets (P < 0.05). Alpha-fetoprotein (AFP) levels in siglec-2 low expression group were significantly higher than those in siglec-2 high expression group using Chi-square analysis (P = 0.043). In addition, both logistic regression analysis and ROC curve method showed that siglec-2 down-regulation in tumor tissues was significantly associated with AFP elevation over 300 ng/ml (P < 0.05). In conclusion, up-regulation of siglec-2 in tumor tissues could predict better OS in HCC patients. Mechanisms of siglec-2 in HCC development need further research.
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Kim J, Choi SJ, Lee SH, Lee HY, Park H. Predicting Survival Using Pretreatment CT for Patients With Hepatocellular Carcinoma Treated With Transarterial Chemoembolization: Comparison of Models Using Radiomics. AJR Am J Roentgenol 2018; 211:1026-1034. [PMID: 30240304 DOI: 10.2214/ajr.18.19507] [Citation(s) in RCA: 89] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
OBJECTIVE The purpose of this study was to investigate the use of radiomics features as prognostic biomarkers for predicting the survival of patients treated with transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). MATERIALS AND METHODS We retrospectively analyzed 88 patients with HCC treated with TACE. High-dimensional quantitative feature analysis was applied to extract 116 radiomics features of pretreatment CT. A radiomics score model was constructed from these features with the use of least absolute shrinkage and selection operator Cox regression. A clinical score model was constructed from clinical variables with the use of multivariate Cox regression. A combined score model was constructed using the radiomics and clinical models. We compared the three models (the radiomics score, clinical score, and combined score models) for predicting overall survival, using Kaplan-Meier analysis and the log-rank test. RESULTS The following radiomics features were selected for the radiomics score model: histogram-based features (median, kurtosis, and energy), shape-based features (spherical disproportion and surface-to-volume ratio), gray-level co-occurrence matrix (GLCM)-based features (energy, informational measure of correlation, maximum probability, contrast, and sum average), and intensity size zone matrix-based features (size zone variability). For the clinical score model, the Child-Pugh score, α-fetoprotein level, and HCC size were included. The combined score model included five radiomics features (surface area-to-volume ratio, kurtosis, median, gray-level co-occurrence matrix contrast, and size zone variability) and three clinical factors (Child-Pugh score, α-fetoprotein level, and HCC size). The combined model was a better predictor of survival (hazard ratio, 19.88; p < 0.0001) than the clinical score model or the radiomics score model. CONCLUSION A radiomics approach combined with conventional clinical variables could be effective in predicting the survival of patients with HCC treated with TACE.
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Affiliation(s)
- Jonghoon Kim
- 1 Department of Electrical and Computer Engineering, Sungkyunkwan University, Suwon, Korea
| | - Seung Joon Choi
- 2 Department of Radiology, Gachon University Gil Medical Center, Incheon, Korea
| | - Seung-Hak Lee
- 1 Department of Electrical and Computer Engineering, Sungkyunkwan University, Suwon, Korea
| | - Ho Yun Lee
- 3 Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Hyunjin Park
- 4 School of Electronic and Electrical Engineering, Sungkyunkwan University, 2066 Seobu-ro Jangan-gu, Suwon, Korea 16419
- 5 Center for Neuroscience Imaging Research, Institute for Basic Science, Suwon, Korea
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Chin KM, Allen JC, Teo JY, Kam JH, Tan EK, Koh Y, Goh KPB, Cheow PC, Raj P, Chow KHP, Chung YFA, Ooi LL, Chan CY, Lee SY. Predictors of post-hepatectomy liver failure in patients undergoing extensive liver resections for hepatocellular carcinoma. Ann Hepatobiliary Pancreat Surg 2018; 22:185-196. [PMID: 30215040 PMCID: PMC6125273 DOI: 10.14701/ahbps.2018.22.3.185] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2018] [Revised: 06/12/2018] [Accepted: 06/14/2018] [Indexed: 12/15/2022] Open
Abstract
Backgrounds/Aims To determine the prevalence of post-hepatectomy liver failure/insufficiency (PHLF/I) in patients undergoing extensive hepatic resections for hepatocellular carcinoma (HCC) and to assess the predictive value of preoperative factors for post-hepatectomy liver failure or insufficiency (PHLF/I). Methods A retrospective review of patients who underwent liver resections for HCC between 2001 and 2013 was conducted. Preoperative parameters were assessed and analyzed for their predictive value of PHLF/I. Definitions used included the 50–50, International Study Group of Liver Surgery (ISGLS) and Memorial Sloan Kettering Cancer Centre (MSKCC) criteria. Results Among the 848 patients who underwent liver resections for HCC between 2001 and 2013, 157 underwent right hepatectomy (RH) and extended right hepatectomy (ERH). The prevalence of PHLF/I was 7%, 41% and 28% based on the 50–50, ISGLS and MSKCC criteria, respectively. There were no significant differences in PHLF/I between RH and ERH. Model for End-Stage Liver Disease (MELD) score and bilirubin were the strongest independent predictors of PHLF/I based on the 50–50 and ISGLS/MSKCC criteria, respectively. Predictive models were developed for each of the criteria with multiple logistic regression. Conclusions MELD score, bilirubin, alpha-fetoprotein and platelet count showed significant predictive value for PHLF/I (all p<0.05). A composite score based on these factors serves as guideline for physicians to better select patients undergoing extensive resections to minimize PHLF.
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Affiliation(s)
- Ken Min Chin
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore
| | - John Carson Allen
- Duke-National University of Singapore (NUS) Medical School, Singapore
| | - Jin Yao Teo
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore.,Duke-National University of Singapore (NUS) Medical School, Singapore
| | - Juinn Huar Kam
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore.,Duke-National University of Singapore (NUS) Medical School, Singapore
| | - Ek Khoon Tan
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore.,Duke-National University of Singapore (NUS) Medical School, Singapore
| | - Yexin Koh
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore
| | - Kim Poh Brian Goh
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore.,Duke-National University of Singapore (NUS) Medical School, Singapore
| | - Peng Chung Cheow
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore.,Duke-National University of Singapore (NUS) Medical School, Singapore
| | - Prema Raj
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore.,Duke-National University of Singapore (NUS) Medical School, Singapore
| | - Kah Hoe Pierce Chow
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore.,Duke-National University of Singapore (NUS) Medical School, Singapore.,Department of Surgical Oncology, National Cancer Centre Singapore, Singapore
| | - Yaw Fui Alexander Chung
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore.,Duke-National University of Singapore (NUS) Medical School, Singapore
| | - London Lucien Ooi
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore.,Duke-National University of Singapore (NUS) Medical School, Singapore
| | - Chung Yip Chan
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore.,Duke-National University of Singapore (NUS) Medical School, Singapore
| | - Ser Yee Lee
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore.,Duke-National University of Singapore (NUS) Medical School, Singapore
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Rungsakulkij N, Suragul W, Mingphruedhi S, Tangtawee P, Muangkaew P, Aeesoa S. Prognostic role of alpha-fetoprotein response after hepatocellular carcinoma resection. World J Clin Cases 2018; 6:110-120. [PMID: 29988930 PMCID: PMC6033749 DOI: 10.12998/wjcc.v6.i6.110] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2018] [Revised: 05/11/2018] [Accepted: 05/30/2018] [Indexed: 02/05/2023] Open
Abstract
AIM To investigate whether the change in pre-/post-operation serum alpha-fetoprotein (AFP) levels is a predictive factor for hepatocellular carcinoma (HCC) outcomes. METHODS We retrospectively analyzed 334 HCC patients who underwent hepatic resection at our hospital between January 2006 and December 2016. The patients were classified into three groups according to their change in serum AFP levels: (1) the normal group, pre-AFP ≤ 20 ng/mL and post-AFP ≤ 20 ng/mL; (2) the response group, pre-AFP > 20 ng/mL and post-AFP decrease of ≥ 50% of pre-AFP; and (3) the non-response group, pre-AFP level > 20 ng/mL and post-AFP decrease of < 50% or higher than pre-AFP level, or any pre-AFP level < 20 ng/mL but post-AFP >20 ng/mL. RESULTS Univariate and multivariate analyses revealed that multiple tumors [hazard ratio (HR): 1.646, 95%CI: 1.15-2.35, P < 0.05], microvascular invasion (mVI) (HR: 1.573, 95%CI: 1.05-2.35, P < 0.05), and the non-response group (HR: 2.425, 95% CI: 1.42-4.13, P < 0.05) were significant independent risk factors for recurrence-free survival. Similarly, multiple tumors (HR: 1.99, 95%CI: 1.12-3.52, P < 0.05), mVI (HR: 3.24, 95%CI: 1.77-5.90, P < 0.05), and the non-response group (HR: 3.62, 95%CI: 1.59-8.21, P < 0.05) were also significant independent risk factors for overall survival. The non-response group had significantly lower overall survival rates and recurrence-free survival rates than both the normal group and the response group (P < 0.05). Thus, patients with no response regarding post-surgery AFP levels were associated with poor outcomes. CONCLUSION Serum AFP responses are significant prognostic factors for the surgical outcomes of HCC patients, suggesting post-resection AFP levels can direct the management of HCC patients.
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Affiliation(s)
- Narongsak Rungsakulkij
- Department of Surgery, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand
| | - Wikran Suragul
- Department of Surgery, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand
| | - Somkit Mingphruedhi
- Department of Surgery, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand
| | - Pongsatorn Tangtawee
- Department of Surgery, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand
| | - Paramin Muangkaew
- Department of Surgery, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand
| | - Suraida Aeesoa
- Department of Surgery, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand
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Rungsakulkij N, Suragul W, Mingphruedhi S, Tangtawee P, Muangkaew P, Aeesoa S. Prognostic factors in patients with HBV-related hepatocellular carcinoma following hepatic resection. Infect Agent Cancer 2018; 13:20. [PMID: 29930697 PMCID: PMC5994073 DOI: 10.1186/s13027-018-0192-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2018] [Accepted: 05/31/2018] [Indexed: 12/17/2022] Open
Abstract
Background To analyze prognostic factors following hepatic resection in patients with HBV-related hepatocellular carcinoma. Methods We retrospectively analyzed 217 patients with HBV-related hepatocellular carcinoma who underwent hepatic resection at our hospital between January 2006 and December 2015. Disease-free survival and overall survival rates were analyzed using the Kaplan–Meier method and the log-rank test. The association between recurrence and survival and various clinicopathological factors, including serum alpha-fetoprotein (AFP) level, platelet count, platelet-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio, antiplatelet therapy, antiviral therapy, hepatitis C virus infection, and tumor-related characteristics, were assessed using univariate and multivariate logistic regression analysis. Results The 1-, 3-, and 5-year overall survival rates were 91, 84, and 79%, respectively, and the recurrence-free survival rates were 72, 51, and 44%, respectively. High post-operative AFP level (hazard ratio [HR] 1.112, 95% confidence interval [CI]: 1.02–1.21, P = 0.007), multiple tumors (HR 1.991, 95% CI: 1.11–3.56, P = 0.021), and no antiviral treatment (HR 1.823, 95% CI: 1.07–3.09, P = 0.026) were independent risk factors for recurrence. High post-operative AFP level (HR 1.222, 95% CI: 1.09–1.36, P < 0.001), multiple tumors (HR 2.715, 95% CI: 1.05–7.02, P = 0.039), and recurrence (HR 12.824, 95% CI: 1.68–97.86, P = 0.014) were independent risk factors for mortality. No other factors analyzed were associated with outcomes in this patient cohort. Conclusions High post-operative serum alpha-fetoprotein level and multiple tumors, but not inflammatory factors, were risk factors for poor prognosis in HBV-related hepatocellular carcinoma patients after resection.
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Affiliation(s)
- Narongsak Rungsakulkij
- Department of Surgery, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 270 Praram VI Road, Ratchathewi, Bangkok, 10400 Thailand
| | - Wikran Suragul
- Department of Surgery, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 270 Praram VI Road, Ratchathewi, Bangkok, 10400 Thailand
| | - Somkit Mingphruedhi
- Department of Surgery, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 270 Praram VI Road, Ratchathewi, Bangkok, 10400 Thailand
| | - Pongsatorn Tangtawee
- Department of Surgery, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 270 Praram VI Road, Ratchathewi, Bangkok, 10400 Thailand
| | - Paramin Muangkaew
- Department of Surgery, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 270 Praram VI Road, Ratchathewi, Bangkok, 10400 Thailand
| | - Suraida Aeesoa
- Department of Surgery, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 270 Praram VI Road, Ratchathewi, Bangkok, 10400 Thailand
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Abdelaziz AO, Shousha HI, Abdelmaksoud AH, Saad Y, Elbaz TM, Soliman ZA, Salah A, Lithy R, Ahmed M, Nabil MM. A new prognostic score can predict survival after hepatocellular carcinoma treatment in a cohort of 1302 Egyptian hepatocellular carcinoma patients. Eur J Gastroenterol Hepatol 2018; 30:514-519. [PMID: 29465472 DOI: 10.1097/meg.0000000000001085] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
INTRODUCTION Survival of hepatocellular carcinoma (HCC) differs between regions and countries according to the different underlying factors and the degree of standard of care that enables early diagnosis and management. Our aim was to identify the most potent predictive factors of survival in Egyptian HCC patients receiving curative or palliative treatments. PATIENTS AND METHODS This retrospective study included 1302 HCC patients attending the HCC multidisciplinary clinic, Cairo University, between February 2009 and December 2016. Clinical, laboratory, tumor characteristics, and treatment data were collected. Prognostic scores for each of the treatment categories, curative or palliative, were developed using routine laboratory tests. RESULTS Patients were predominantly men, mean age 57.79±7.56 years. All cases developed HCC in addition to cirrhosis, mainly hepatitis C virus-related (88.2%). Most of the patients were Child-Pugh A (56.8%) or B (34.4%) and had single lesions. Transarterial chemoembolization was the most common line of treatment (42.08%). The overall median survival was 18.3 months from the date of diagnosis. Cigarette smoking, Child-Pugh score, performance status, number and size of the focal lesion, α-fetoprotein, and application of a specific treatment, particularly curative treatment, were the significant independent prognostic factors for survival. We found no impact of diabetes mellitus or hypertension on survival. Multidisciplinary HCC clinic predictive scores of survival after palliative and curative treatments were developed including independent prognostic factors, age, and portal vein status. CONCLUSION A new Egyptian prognostic score of tumor and patients factors can predict the survival of patients with HCC after palliative and curative treatments.
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Affiliation(s)
| | - Hend I Shousha
- Departments of Endemic Medicine and Hepatogastroenterology
| | | | - Yasmin Saad
- Departments of Endemic Medicine and Hepatogastroenterology
| | - Tamer M Elbaz
- Departments of Endemic Medicine and Hepatogastroenterology
| | | | - Ayman Salah
- General Surgery, Liver Surgery Unit, Faculty of Medicine, Cairo University, Egypt
| | - Rania Lithy
- Departments of Endemic Medicine and Hepatogastroenterology
| | - Mona Ahmed
- Departments of Endemic Medicine and Hepatogastroenterology
- Al-Razi general hospital authority of Abyan, Yemen
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Serum alpha-fetoprotein level per total tumor volume as a predictor of recurrence of hepatocellular carcinoma after resection. Surgery 2017; 163:1002-1007. [PMID: 29284589 DOI: 10.1016/j.surg.2017.10.063] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2017] [Revised: 10/18/2017] [Accepted: 10/24/2017] [Indexed: 02/08/2023]
Abstract
BACKGROUND Alpha-fetoprotein has been used as a predictor of recurrence for hepatocellular carcinoma and disease-free survival post-resection. Studies in East Asia have shown that serum alpha-fetoprotein per total tumor volume ratio is a better prognostic indicator than alpha-fetoprotein alone. Similar studies in the United States evaluating serum alpha-fetoprotein to total tumor volume ratio have not been conducted. Its relevance is incompletely understood. METHODS Consecutive patients undergoing resection for hepatocellular carcinoma at a single tertiary center between 2000 and 2013 were identified for inclusion in this retrospective cohort study. Patient demographics, associated liver disease, Child-Pugh and Model for End-Stage Liver Disease scores, preoperative imaging, surgical pathology, alpha-fetoprotein at diagnosis, last alpha-fetoprotein before surgery, and peak alpha-fetoprotein levels were recorded. Actual tumor volume by imaging volumetrics was used when available (n = 70). For the remaining cases, total tumor volume was calculated using the sum of the volumes of all the tumors ((4/3)πr3) where "r" is the mean radius of each lesion. Peak serum alpha-fetoprotein was used to calculate the alpha-fetoprotein to total tumor volume ratio. RESULTS A total of 124 patients resected for hepatocellular carcinoma between 2000 and 2013 were identified. Overall 1-, 3-, and 5-year survival post resection was 76%, 53%, and 35%, respectively. On multivariate analysis, peak alpha-fetoprotein to total tumor volume ratio > 20 (P < .001, HR = 3.72, 95% CI [1.82-7.58]) and lymphovascular space invasion (P = .002, HR = 3.30, 95% CI [1.57-6.94]) were found to affect hepatocellular carcinoma recurrence-free survival. CONCLUSION A variety of prognostic values predict the recurrence of hepatocellular carcinoma postresection. Peak preoperative alpha-fetoprotein to total tumor volume > 20 and lymphovascular space invasion has been shown to predict recurrence of hepatocellular carcinoma. Our study confirms findings from East Asian studies. But larger series are needed to establish this correlation in patients with hepatocellular carcinoma not treated by resection.
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Kuo HT, Que J, Lin LC, Yang CC, Koay LB, Lin CH. Impact of tumor size on outcome after stereotactic body radiation therapy for inoperable hepatocellular carcinoma. Medicine (Baltimore) 2017; 96:e9249. [PMID: 29390360 PMCID: PMC5815772 DOI: 10.1097/md.0000000000009249] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/23/2023] Open
Abstract
Stereotactic body radiation therapy (SBRT) for inoperable hepatocellular carcinoma (HCC) offers excellent local control rates. This study retrospectively analyzed the influence of different tumor size on treatment outcomes after SBRT.Between December 2008 and February 2014, 141 HCC patients were treated with Cyberknife SBRT. Patients were divided into 3 groups namely small tumors (≤4 cm), intermediate-sized (>4-<10 cm), and large (≥10 cm) tumors. Treatment outcomes, prognoses, and safety at each tumor size were compared and analyzed.A total of 52 patients with small tumors, 55 with intermediate tumors, and 34 patients with large tumors were retrospectively analyzed with a median follow-up of 16 months. Objective responses were achieved at 96.15%, 90.90%, and 76.47% for small, intermediate, and large tumors, respectively (P ≤ .0001) and the 3-year local control rates were 97.85%, 71.99%, and 82.14%, respectively (P = .0035). The 3-year overall survival rates were 50.26%, 45.29%, and 33.38% for small, intermediate, and large tumors, respectively (P = .3757). No significant differences were found in overall-survival, intra-hepatic recurrence free survival, disease-progression free survival, or distant metastasis-free survival.SBRT offers the best effective local control rate and response rate for small HCCs. However, tumor size did not significantly affect the overall survival rate, intra-hepatic recurrence free rate, or disease-progression free rate.
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Affiliation(s)
- Hsing-Tao Kuo
- Department of Internal Medicine, Division of Hepatology, Chi Mei Medical Center
- Department of Senior Citizen Service Management, Chia Nan University of Pharmacy and Science, Tainan, Taiwan
| | - Jenny Que
- Department of Radiation Oncology
- Department of Hospital and Health Care Administration
| | - Li-Ching Lin
- Department of Radiation Oncology
- Department of Optometry, Chung Hwa University of Medical Technology
| | | | - Lok-Beng Koay
- Department of Internal Medicine, Division of Hepatology, Chi Mei Medical Center
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Abstract
The encouraging results in immunotherapy for melanoma also led the way for translational and clinical research about immune-related mechanisms possibly relevant for gastrointestinal tumours. It is in fact now evident that the immune checkpoint modulation and in particular cell-mediated immune-response through programmed cell death-1 (PD-1) and the cytotoxic T-lymphocyte antigen-4 (CTLA4) receptors along with the regulatory T cells activity all have a relevant role in gastrointestinal cancers as well. This review aims to explore the state of the art of immunotherapy for gastrointestinal tumours, deepening recent scientific evidence regarding anti PD-1/PDL-1 and anti CTLA4 monoclonal antibodies, peptide based vaccine, DNA based vaccine, and pulsed dendritic cells, either alone or in combination with other antineoplastic medical therapy and locoregional treatments. Considering the non-negligible toxicity profile deriving from such a treatment approach, predictive biomarkers of response to immunotherapy in gastrointestinal cancer are also urgently needed in order to better select the patients' group with the highest likelihood of benefit.
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Jin C, Li C, Peng W, Wen TF, Yan LN, Li B, Wang WT, Yang JY, Xu MQ. Changes of platelet times neutrophil to lymphocyte ratio predict BCLC stage A hepatocellular carcinoma survival. Medicine (Baltimore) 2017; 96:e7821. [PMID: 28816981 PMCID: PMC5571718 DOI: 10.1097/md.0000000000007821] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Platelet, neutrophil, and lymphocyte ratio (PNLR) has its own unique role in influencing postoperative recurrence for patients with hepatocellular carcinoma (HCC). Surgical stress can change systemic inflammatory response of patients. Thus the aim of this study was to identify the prognostic value of changes of platelet times neutrophil to lymphocyte ratio in hepatitis B related HCC within Barcelona clinical liver cancer (BCLC) stage A.Data of patients with HCC within BCLC stage A were reviewed. Pre-, intra- and postoperative variables were retrospectively and statistically analyzed. The postoperative variable was calculated based on the data obtained on the first postoperative month following liver resection.A total of 556 patients were included in present study. During the follow-up period, 257 patients experienced recurrence and 150 patients died. Multivariate analyses suggested multiple tumors (hazard ratio [HR] = 2.409; 95% confidence interval [CI] = 1.649-3.518; P < .001), microvascular invasion (MVI) (HR = 1.585; 95% CI = 1.219-2.061; P = .001), and increased postoperative PNLR (HR = 1.900; 95% CI = 1.468-2.457; P < .001) independently associated with postoperative recurrence, whereas MVI (HR = 1.834; 95% CI = 1.324-2.542; P < .001), postoperative neutrophil to lymphocyte ratio (NLR) (HR = 1.151; 95% CI = 1.025-1.294; P = .018) and increased postoperative PNLR (HR = 2.433; 95% CI = 1.667-3.550; P < .001) contributed to postoperative mortality. The 5-year recurrence-free survival and overall survival rates of patients with increased postoperative PNLR (N = 285) versus those with decreased postoperative PNLR (N = 271) were 36.8% versus 61.5% and 47.6% versus 76.4% respectively (P < .001).Changes of PNLR was a powerful prognostic indicator of poor outcomes in patients with HCC within BCLC stage A. PNLR should be monitored in our postoperative follow-up.
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Yang W, Wu H, Zhang ZY, Lee JC, Wang S, Wang YJ, Wu W, Chen MH, Yan K. Long-term outcome of percutaneous radiofrequency ablation in recurrent hepatocellular carcinoma after liver transplantation. Int J Hyperthermia 2017; 34:68-76. [PMID: 28540818 DOI: 10.1080/02656736.2017.1324179] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Affiliation(s)
- Wei Yang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Ultrasound, Peking University Cancer Hospital and Institute, Haidian District, Beijing, China
| | - Hao Wu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Ultrasound, Peking University Cancer Hospital and Institute, Haidian District, Beijing, China
- Department of Ultrasound, The Third Affiliated Hospital of Southern Medical University (Academy of Orthopedics Guangdong Province), Guangzhou, China
| | - Zhong-yi Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Ultrasound, Peking University Cancer Hospital and Institute, Haidian District, Beijing, China
| | - Jung-chieh Lee
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Ultrasound, Peking University Cancer Hospital and Institute, Haidian District, Beijing, China
| | - Song Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Ultrasound, Peking University Cancer Hospital and Institute, Haidian District, Beijing, China
| | - Yan-jie Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Ultrasound, Peking University Cancer Hospital and Institute, Haidian District, Beijing, China
| | - Wei Wu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Ultrasound, Peking University Cancer Hospital and Institute, Haidian District, Beijing, China
| | - Min-hua Chen
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Ultrasound, Peking University Cancer Hospital and Institute, Haidian District, Beijing, China
| | - Kun Yan
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Ultrasound, Peking University Cancer Hospital and Institute, Haidian District, Beijing, China
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Zhao Y, Li H, Bai W, Liu J, Lv W, Sahu S, Guan S, Qin X, Wang W, Ren W, Mu W, Guo W, Gu S, Ma Y, Yin Z, Guo W, Wang W, Wang Y, Duran R, Fan D, Zhang Z, Han G. Early sorafenib-related adverse events predict therapy response of TACE plus sorafenib: A multicenter clinical study of 606 HCC patients. Int J Cancer 2017; 139:928-37. [PMID: 27038145 DOI: 10.1002/ijc.30124] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2015] [Revised: 02/04/2016] [Accepted: 03/22/2016] [Indexed: 12/18/2022]
Abstract
The purpose of our study was to test the hypothesis that sorafenib-related dermatologic adverse events (AEs) as an early biomarker can predict the long-term outcomes following the combination therapy of transarterial chemoembolization (TACE) plus sorafenib (TACE-S). The intermediate-stage hepatocellular carcinoma patients who received either TACE-S or TACE-alone treatment were consecutively included into analysis. In the TACE-S group, patients with ≥ grade 2 dermatologic AEs within the first month of sorafenib initiation were defined as responders; whereas those with < grade 2 were defined as nonresponders. In the TACE-S group, the median overall survival (OS) of the responders was significantly longer than that of nonresponders (28.9 months vs. 16.8 months, respectively; p = 0.004). Multivariate analysis demonstrated that nonresponders were significantly associated with an increased risk of death compared with responders (HR = 1.9; 95% confidence Interval-CI: 1.3-2.7; p = 0.001). The survival analysis showed that the median OS was 27.9 months (95% CI: 25.0-30.8) among responders treated with TACE-S vs.18.3 months (95% CI: 14.5-22.1) among those who received TACE-alone (p = 0.046). The median time to progression was 13.1 months (95% CI: 4.4-21.8) in the TACE-S group, a duration that was significantly longer than that in the TACE-alone group [5 months (95% CI: 6.4-13.3), p = 0.014]. This study demonstrated that sorafenib-related dermatologic AEs are clinical biomarkers to identify responders from all of the patients for TACE-S therapy. Sorafenib-related dermatologic AEs, clinical biomarkers, can predict the efficacy of TACE-S in future randomized controlled trials.
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Affiliation(s)
- Yan Zhao
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Hailiang Li
- Department of Interventional Radiology, Henan Cancer Hospital, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China
| | - Wei Bai
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Jueshi Liu
- Department of Interventional Radiology and Vascular Surgery, Hunan Provincial People's Hospital, Changsha, China
| | - Weifu Lv
- Department of Radiology, Anhui Provincial Hospital, Hefei, China
| | - Sonia Sahu
- Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston
| | - Sheng Guan
- Second Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Xiao Qin
- Department of Hepatobiliary Surgery & Vascular Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Wenhui Wang
- Department of Interventional Medicine, The First Affiliated Hospital of Lanzhou University, Lanzhou, China
| | - Weixin Ren
- Department of Interventional Radiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Wei Mu
- Department of Radiology, The Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Weidong Guo
- Cancer Treatment Center, Baogang Hospital of Inner Mongolia, Baotou, China
| | - Shanzhi Gu
- Department of Interventional Radiology, Hunan Cancer Hospital of Central South University, Changsha, China
| | - Yilong Ma
- Department of Interventional Therapy, Tumor Hospital of Guangxi Medical University, Nanning, China
| | - Zhanxin Yin
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Wengang Guo
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Wenjun Wang
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Yongji Wang
- Department of Medical Statistics, Fourth Military Medical University, Xi'an, China
| | - Rafael Duran
- Department of Radiology, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland
| | - Daiming Fan
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China.,State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Zhuoli Zhang
- Department of Radiology, Northwestern University, Chicago
| | - Guohong Han
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China
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Chen Y, Li L, Qian X, Ge Y, Xu G. High expression of TRIM11 correlates with poor prognosis in patients with hepatocellular carcinoma. Clin Res Hepatol Gastroenterol 2017; 41:190-196. [PMID: 28065743 DOI: 10.1016/j.clinre.2016.09.010] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2016] [Revised: 09/20/2016] [Accepted: 09/27/2016] [Indexed: 02/08/2023]
Abstract
BACKGROUND Tripartite Motif Containing 11 (TRIM11), a member of TRIM proteins is overexpressed in gliomas and lung cancer. However, the role of TRIM11 in hepatocellular carcinoma (HCC) is unknown. BASIC PROCEDURES Herein, we aimed to investigate the expression and clinical significance role of TRIM11 in HCC. MAIN FINDING In this study, our data showed significant higher TRIM11 in HCC tissues (n=117) than in the matched non-tumor liver (NTL) tissues (P<0.01). In consistent with above data, we also found TRIM11 protein expression was significantly increased compared with the matched NTL (P<0.01) by immunohistochemistry analysis. Additionally, our results showed that TRIM11 protein expression in HCC tissues was significantly associated with pathological grade (P<0.01), tumor postoperative metastasis (P=0.031), recurrence (P=0.022), and serum a-fetoprotein (AFP) (P<0.01). Moreover, patients' survival was negatively correlated with TRIM11 protein expression. Furthermore, we found that TRIM11 protein was an independent prognostic factor for disease-free (P<0.01) and overall survival (P<0.01) in HCC patients. PRINCIPAL CONCLUSIONS Our data showed that TRIM11 expression was significantly elevated in HCC tissues. The overexpression of TRIM11 is closely associated with HCC progression and poor survival of the patients, indicating TRIM11 is a potential therapeutic target for HCC patients.
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Affiliation(s)
- Yue Chen
- Anhui Medical University, No. 81 Meishan Road, Hefei 230032, China; Anhui Provincial Hospital, No. 17 Lujiang Road, Hefei 230001, China; Department of General Surgery, Hefei Second People's Hospital, No. 246 Heping Road, Hefei 230011, China
| | - Liang Li
- Department of General Surgery, Hefei Second People's Hospital, No. 246 Heping Road, Hefei 230011, China
| | - Xiaoxing Qian
- Department of General Surgery, Hefei Second People's Hospital, No. 246 Heping Road, Hefei 230011, China
| | - Yongsheng Ge
- Department of Hepatic Surgery, Anhui Provincial Hospital, No. 17 Lujiang Road, Hefei 230001, China
| | - Geliang Xu
- Anhui Medical University, No. 81 Meishan Road, Hefei 230032, China; Department of Hepatic Surgery, Anhui Provincial Hospital, No. 17 Lujiang Road, Hefei 230001, China.
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Wang J, Mao Y, Liu Y, Chen Z, Chen M, Lao X, Li S. Hepatocellular Carcinoma in Children and Adolescents: Clinical Characteristics and Treatment. J Gastrointest Surg 2017; 21:1128-1135. [PMID: 28397025 PMCID: PMC5486687 DOI: 10.1007/s11605-017-3420-3] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2017] [Accepted: 03/30/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) occurs rarely in children and adolescents (C&A), and its clinical characteristics, prognostic factors, and treatment were rarely explored. METHODS This retrospective study focused on 65 HCC patients aged ≤20 years from August 1994 to August 2012. Cox regression models and Kaplan-Meier curves were used to investigate prognostic factors and compare overall survival (OS), respectively. RESULTS We found 61.5% of patients to have multiple tumors, 30.8% to have portal vein tumor thrombus, and 16.9% to have distant metastasis. Diameter of tumors was 10.2 ± 4.1 cm. OS at 5 years was 15.8%. Multivariate analyses showed initial treatment (P < 0.001) to be a predictor for OS. For moderate-stage HCC, the median OS of patients who underwent resection was longer than that of patients who underwent transarterial chemoembolization (TACE) or supportive treatment (ST) (P < 0.001). For advanced-stage HCC, the median OS of patients who underwent TACE was longer than that of patients who underwent ST (P = 0.045). CONCLUSIONS HCC in C&A tends to be more advanced than that in adults, and resection remains the mainstay of treatment for those patients. Moreover, compared with ST, TACE may benefit C&A with moderate- and advanced-stage HCC, which needs further study.
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Affiliation(s)
- Juncheng Wang
- 0000 0001 2360 039Xgrid.12981.33Department of Hepatobiliary Oncology, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, No. 651 Dongfeng Road East, Guangzhou, 510060 China
| | - Yize Mao
- 0000 0001 2360 039Xgrid.12981.33Department of Hepatobiliary Oncology, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, No. 651 Dongfeng Road East, Guangzhou, 510060 China
| | - Yongcheng Liu
- 0000 0001 2360 039Xgrid.12981.33Department of Hepatobiliary Oncology, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, No. 651 Dongfeng Road East, Guangzhou, 510060 China ,0000 0004 1759 700Xgrid.13402.34Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310020 China
| | - Zhenxin Chen
- 0000 0001 2360 039Xgrid.12981.33Department of Hepatobiliary Oncology, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, No. 651 Dongfeng Road East, Guangzhou, 510060 China
| | - Minshan Chen
- 0000 0001 2360 039Xgrid.12981.33Department of Hepatobiliary Oncology, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, No. 651 Dongfeng Road East, Guangzhou, 510060 China
| | - Xiangming Lao
- 0000 0001 2360 039Xgrid.12981.33Department of Hepatobiliary Oncology, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, No. 651 Dongfeng Road East, Guangzhou, 510060 China
| | - Shengping Li
- 0000 0001 2360 039Xgrid.12981.33Department of Hepatobiliary Oncology, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, No. 651 Dongfeng Road East, Guangzhou, 510060 China
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Li W, Wang Y, Gao W, Zheng J. Combination of transcatheter arterial chemoembolization and CT-guided percutaneous segment ablation for hepatocellular carcinoma therapy: A retrospective study. Medicine (Baltimore) 2016; 95:e5422. [PMID: 27893681 PMCID: PMC5134874 DOI: 10.1097/md.0000000000005422] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Treatment option for liver cancer patients with large tumor >5 cm and/or portal vein tumor thrombosis is very limited. New treatment strategy is badly needed. Our study is to determine the safety and treatment efficacy of a new minimally invasive treatment strategy-liver segment thermal ablation.Late-stage hepatocellular carcinoma patients were included and treated with percutaneous ablation to destroy the entire tumor-containing liver segment to reduce reoccurrence and prolong survival. Transcatheter arterial chemoembolization was used before ablation to label tumor margin. The patients were followed up routinely.The patients were followed up for 8 to 95 months. Mean overall survival (OS) (n = 6) was 21.5 months (range 8-95). For patients in BCLC stage B (n = 2), average OS was 16 months; for those in stage C (n = 4), mean OS was 25 months (range 15-95). Out of all 6 patients, 2 reoccurred within 1 year, and 1 reoccurred after 13 months postoperatively. The average alpha-fetoprotein was dropped from 1153.69 to 41.22 μg/L postoperatively. No severe intra or postoperative complications were observed.Our preliminary data indicated that transcatheter arterial chemoembolization + segment ablation is safe and benefits survival significantly for late-stage hepatocellular carcinoma patients. A prospective multicenter, randomized trial comparing focal and segment ablation is now ongoing in China (Trial Registry Number, ChiCTR-TRC-12002786).
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Dohi C, Nouso K, Miyahara K, Morimoto Y, Wada N, Kinugasa H, Takeuchi Y, Kuwaki K, Onishi H, Ikeda F, Nakamura S, Shiraha H, Takaki A, Okada H. Potential of alpha-fetoprotein as a prognostic marker after curative radiofrequency ablation of hepatocellular carcinoma. Hepatol Res 2016; 46:916-923. [PMID: 26670077 DOI: 10.1111/hepr.12636] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2015] [Revised: 12/02/2015] [Accepted: 12/06/2015] [Indexed: 02/08/2023]
Abstract
AIM Recurrence of hepatocellular carcinoma (HCC) is observed frequently, even after curative treatments. The aim of this study is to elucidate the risk factors for recurrence of HCC after radiofrequency ablation (RFA), focusing on the carcinogenic potential of the liver assessed by α-fetoprotein (AFP). METHODS We enrolled 357 consecutive patients who underwent complete ablation by RFA for primary HCC (≤3 cm, ≤3 tumors) and analyzed the correlation between 17 critical parameters, including AFP and HCC recurrence. RESULTS Recurrence was observed in 236 patients during a mean observation period of 54.3 months. Multivariate analysis revealed that multiple tumors (risk ratio [RR] = 1.70, 95% confidence interval [CI] = 1.27-2.26, P < 0.001), high AFP (>10 ng/mL, RR = 1.45, 95% CI = 1.09-1.94, P < 0.001) and high des-γ-carboxyprothrombin (>40 mAU/mL, RR = 1.52, 95% CI = 1.13-2.02, P < 0.005) were significantly correlated with recurrence. AFP was selected as a significant factor even when the cut-off level was set lower (≤5 ng/mL). The risk of recurrence increased linearly according to the increase of the lowest AFP level after RFA and the adjusted ratios relative to AFP less than 5 ng/mL were 1.56, 2.14, 2.57 and 3.13 in AFP 5-10 ng/mL, 10-20 ng/mL, 20-50 ng/mL and over 50 ng/mL, respectively. In addition, the recurrence rate was predicted by the AFP level after RFA, regardless of the level before the treatment. CONCLUSION AFP less than 5 ng/mL after curative RFA was an important predictor of a better prognosis and was considered to indicate the low carcinogenic potential of the non-cancerous liver.
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Affiliation(s)
- Chihiro Dohi
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Kazuhiro Nouso
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
- Department of Gastroenterology, Okayama City Hospital, Okayama, Japan
| | - Koji Miyahara
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Yuki Morimoto
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Nozomu Wada
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Hideaki Kinugasa
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Yasuto Takeuchi
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Kenji Kuwaki
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Hideki Onishi
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Fusao Ikeda
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Shinichiro Nakamura
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Hidenori Shiraha
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Akinobu Takaki
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Hiroyuki Okada
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
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Charrière B, Maulat C, Suc B, Muscari F. Contribution of alpha-fetoprotein in liver transplantation for hepatocellular carcinoma. World J Hepatol 2016; 8:881-890. [PMID: 27478538 PMCID: PMC4958698 DOI: 10.4254/wjh.v8.i21.881] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2016] [Revised: 05/30/2016] [Accepted: 06/29/2016] [Indexed: 02/06/2023] Open
Abstract
Alpha-fetoprotein (AFP) is the main tumor biomarker available for the management of hepatocellular carcinoma (HCC). Although it is neither a good screening test nor an accurate diagnostic tool for HCC, it seems to be a possible prognostic marker. However, its contribution in liver transplantation for HCC has not been fully determined, although its use to predict recurrence after liver transplantation has been underlined by international societies. In an era of organ shortages, it could also have a key role in the selection of patients eligible for liver transplantation. Yet unanswered questions remain. First, the cut-off value of serum AFP above which liver transplantation should not be performed is still a subject of debate. We show that a concentration of 1000 ng/mL could be an exclusion criterion, whereas values of < 15 ng/mL indicate patients with an excellent prognosis whatever the size and number of tumors. Monitoring the dynamics of AFP could also prove useful. However, evidence is lacking regarding the values that should be used. Today, the real input of AFP seems to be its integration into new criteria to select patients eligible for a liver transplantation. These recent tools have associated AFP values with morphological criteria, thus refining pre-existing criteria, such as Milan, University of California, San Francisco, or “up-to-seven”. We provide a review of the different criteria submitted within the past years. Finally, AFP can be used to monitor recurrence after transplantation, although there is little evidence to support this claim. Future challenges will be to draft new international guidelines to implement the use of AFP as a selection tool, and to determine a clear cut-off value above which liver transplantation should not be performed.
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Higher Ratio of Serum Alpha-Fetoprotein Could Predict Outcomes in Patients with Hepatitis B Virus-Associated Hepatocellular Carcinoma and Normal Alanine Aminotransferase. PLoS One 2016; 11:e0157299. [PMID: 27304617 PMCID: PMC4909194 DOI: 10.1371/journal.pone.0157299] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2016] [Accepted: 05/26/2016] [Indexed: 12/14/2022] Open
Abstract
Background The role of serum alpha-fetoprotein (AFP) levels in the surveillance and diagnosis of hepatocellular carcinoma (HCC) is controversial. The aim of this study was to investigate the value of serially measured serum AFP levels in HCC progression or recurrence after initial treatment. Methods A total of 722 consecutive patients newly diagnosed with HCC and treated at the National Cancer Center, Korea, between January 2004 and December 2009 were enrolled. The AFP ratios between 4–8 weeks post-treatment and those at the time of HCC progression or recurrence were obtained. Multivariate logistic regression analysis was performed to correlate the post-treatment AFP ratios with the presence of HCC progression or recurrence. Results The etiology of HCC was related to chronic hepatitis B virus (HBV) infection in 562 patients (77.8%), chronic hepatitis C virus (HCV) infection in 74 (10.2%), and non-viral cause in 86 (11.9%). There was a significant decrease in serum AFP levels from the baseline to 4 to 8 weeks after treatment (median AFP, 319.6 ng/mL vs. 49.6 ng/mL; p< 0.001). Multivariate analysis showed that an AFP ratio > 1.0 was an independently associated with HCC progression or recurrence. Among the different causes of HCC analyzed, this association was significant only for HCC related to chronic hepatitis B (p< 0.001) and non-viral causes (p<0.05), and limited only to patients who had normal alanine aminotransferase (ALT) levels. Conclusion Serial measurements of serum AFP ratios could be helpful in detecting progression or recurrence in treated patients with HBV-HCC and normal ALT.
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Rapisarda V, Loreto C, Malaguarnera M, Ardiri A, Proiti M, Rigano G, Frazzetto E, Ruggeri MI, Malaguarnera G, Bertino N, Malaguarnera M, Catania VE, Di Carlo I, Toro A, Bertino E, Mangano D, Bertino G. Hepatocellular carcinoma and the risk of occupational exposure. World J Hepatol 2016; 8:573-90. [PMID: 27168870 PMCID: PMC4858622 DOI: 10.4254/wjh.v8.i13.573] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2015] [Revised: 04/01/2016] [Accepted: 04/14/2016] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common type of liver cancer. The main risk factors for HCC are alcoholism, hepatitis B virus, hepatitis C virus, nonalcoholic steatohepatitis, obesity, type 2 diabetes, cirrhosis, aflatoxin, hemochromatosis, Wilson's disease and hemophilia. Occupational exposure to chemicals is another risk factor for HCC. Often the relationship between occupational risk and HCC is unclear and the reports are fragmented and inconsistent. This review aims to summarize the current knowledge regarding the association of infective and non-infective occupational risk exposure and HCC in order to encourage further research and draw attention to this global occupational public health problem.
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Affiliation(s)
- Venerando Rapisarda
- Venerando Rapisarda, Dario Mangano, Occupational Medi-cine Unit, Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy
| | - Carla Loreto
- Venerando Rapisarda, Dario Mangano, Occupational Medi-cine Unit, Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy
| | - Michele Malaguarnera
- Venerando Rapisarda, Dario Mangano, Occupational Medi-cine Unit, Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy
| | - Annalisa Ardiri
- Venerando Rapisarda, Dario Mangano, Occupational Medi-cine Unit, Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy
| | - Maria Proiti
- Venerando Rapisarda, Dario Mangano, Occupational Medi-cine Unit, Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy
| | - Giuseppe Rigano
- Venerando Rapisarda, Dario Mangano, Occupational Medi-cine Unit, Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy
| | - Evelise Frazzetto
- Venerando Rapisarda, Dario Mangano, Occupational Medi-cine Unit, Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy
| | - Maria Irene Ruggeri
- Venerando Rapisarda, Dario Mangano, Occupational Medi-cine Unit, Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy
| | - Giulia Malaguarnera
- Venerando Rapisarda, Dario Mangano, Occupational Medi-cine Unit, Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy
| | - Nicoletta Bertino
- Venerando Rapisarda, Dario Mangano, Occupational Medi-cine Unit, Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy
| | - Mariano Malaguarnera
- Venerando Rapisarda, Dario Mangano, Occupational Medi-cine Unit, Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy
| | - Vito Emanuele Catania
- Venerando Rapisarda, Dario Mangano, Occupational Medi-cine Unit, Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy
| | - Isidoro Di Carlo
- Venerando Rapisarda, Dario Mangano, Occupational Medi-cine Unit, Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy
| | - Adriana Toro
- Venerando Rapisarda, Dario Mangano, Occupational Medi-cine Unit, Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy
| | - Emanuele Bertino
- Venerando Rapisarda, Dario Mangano, Occupational Medi-cine Unit, Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy
| | - Dario Mangano
- Venerando Rapisarda, Dario Mangano, Occupational Medi-cine Unit, Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy
| | - Gaetano Bertino
- Venerando Rapisarda, Dario Mangano, Occupational Medi-cine Unit, Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy
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Gai JQ, Sheng X, Qin JM, Sun K, Zhao W, Ni L. The effect and mechanism of bufalin on regulating hepatocellular carcinoma cell invasion and metastasis via Wnt/β-catenin signaling pathway. Int J Oncol 2015; 48:338-48. [PMID: 26648168 DOI: 10.3892/ijo.2015.3250] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2015] [Accepted: 10/11/2015] [Indexed: 01/30/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a highly malignant tumor with an extremely poor prognosis. Our preliminary study indicated that bufalin could restrain the proliferation of human hepatoma BEL-7402 cells in a time- and dose-dependent manner. In the present study, the colony formation assay, the Transwell invasion assay, the western blot analysis and the immunofluorescence method were respectively used to investigate the effect and mechanism of bufalin against HCC cell invasion and metastasis. We found that: i) bufalin had significant inhibitory effect on the cell proliferation of BEL-7402 cells; ii) bufalin markedly inhibited the migration and invasion of BEL-7402 cells; iii) bufalin could suppress the phosphorylation of GSK-3β Ser9 site in BEL-7402 cells, decrease the expression of β-catenin, cyclin D1, metalloproteinases-7 (MMP-7) and cyclooxygenase-2 (COX-2) in the cytoplasm, and increase the expression of E-cadherin and β-catenin on the cell membrane; and iv) the expression of α-fetoprotein significantly decreased and the expression of albumin increased in BEL-7402 cells after bufalin was used. Our results indicate that: i) bufalin can regulate the expression of associated factors in Wnt/β-catenin signaling pathway of BEL-7402 cells through suppressing the phosphorylation of GSK-3β Ser9 site; ii) bufalin can strengthen intercellular E-cadherin/β-catenin complex to control epithelial-mesenchymal transition; and iii) bufalin can reverse the malignant phenotype and promote the differentiation and maturation by regulating the AFP and ALB expression in BEL-7402 cells. These are very important mechanisms of bufalin on the inhibition of the invasion and metastasis of HCC cells.
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Affiliation(s)
- Ji Qin Gai
- Department of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China
| | - Xia Sheng
- Department of Pathology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China
| | - Jian Min Qin
- Department of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China
| | - Kang Sun
- Department of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China
| | - Wei Zhao
- Department of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China
| | - Lei Ni
- Department of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China
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Serum levels of chemokines CCL4 and CCL5 in cirrhotic patients indicate the presence of hepatocellular carcinoma. Br J Cancer 2015; 113:756-62. [PMID: 26270232 PMCID: PMC4559820 DOI: 10.1038/bjc.2015.227] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Revised: 03/03/2015] [Accepted: 05/13/2015] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Most hepatocellular carcinomas (HCCs) are diagnosed at an advanced stage. The prognostic value of serum tumour markers alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) is limited. The aim of our study is to evaluate the diagnostic value of serum growth factors, apoptotic and inflammatory mediators of cirrhotic patients with and without HCC. METHODS Serum samples were collected from cirrhotic potential liver transplant patients (LTx) with (n=61) and without HCC (n=78) as well as from healthy controls (HCs; n=39). Serum concentrations of CRP, neopterin and IL-6 as markers of inflammation and thrombopoietin (TPO), GCSF, FGF basic and VEGF, HMGB1, CK-18 (M65) and CK18 fragment (M30) and a panel of proinflammatory chemokines (CCL2, CCL3, CCL4, CCL5, CXCL5 and IL-8) were measured. Chi square, Fisher exact, Mann-Whitney U-tests, ROC curve analysis and forward stepwise logistic regression analyses were applied. RESULTS Patients with HCC had higher serum TPO and chemokines (P<0.001 for TPO, CCL4, CCL5 and CXCL5) and lower CCL2 (P=0.008) levels than cirrhotic patients without HCC. Multivariate forward stepwise regression analysis for significant parameters showed that among the studied parameters CCL4 and CCL5 (P=0.001) are diagnostic markers of HCC. Serum levels of TPO and chemokines were lower, whereas M30 was significantly higher in cirrhotic patients than in HCs. CONCLUSIONS High serum levels of inflammatory chemokines such as CCL4 and CCL5 in the serum of cirrhotic patients indicate the presence of HCC.
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Qi X, Wang D, Su C, Li H, Guo X. Hepatic resection versus transarterial chemoembolization for the initial treatment of hepatocellular carcinoma: A systematic review and meta-analysis. Oncotarget 2015; 6:18715-33. [PMID: 26243835 PMCID: PMC4621923 DOI: 10.18632/oncotarget.4134] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2015] [Accepted: 04/23/2015] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND & AIMS According to the Barcelona Clinic Liver Cancer (BCLC) staging system, hepatic resection and transarterial chemoembolization (TACE) should be recommended in patients with hepatocellular carcinoma (HCC) within and beyond the BCLC stage A, respectively. We conducted a systematic review and meta-analysis to compare the overall survival between HCC patients undergoing hepatic resection and TACE. METHODS PubMed, EMBASE, and Cochrane library databases were searched. All relevant studies were considered, if they reported the survival data in HCC patients undergoing hepatic resection and TACE. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated for the comparison of cumulative overall survival. Odds ratios (ORs) with 95%CIs were calculated for the comparison of 1-, 3-, and 5-year survival rates. Subgroup analyses were performed according to the BCLC stages and portal vein tumor thrombus (PVTT). Sensitivity analyses were performed in moderate- and high-quality studies and in studies published after 2005. RESULTS Fifty of 2029 retrieved papers were included. One, 15, and 34 studies were of high-, moderate-, and low-quality, respectively. The overall meta-analysis demonstrated a statistically significantly higher overall survival in hepatic resection group than in TACE group (HR=0.60, 95%CI=0.55-0.66). Additionally, 1-, 3-, and 5-year survival rates were statistically significantly higher in hepatic resection group than in TACE group (OR=1.82, 95%CI=1.56-2.14; OR=3.09, 95%CI=2.60-3.67; OR=3.48, 95%CI=2.83-4.27). The subgroup meta-analyses confirmed the statistical significance in HCC within the BCLC stage A (HR=0.72, 95%CI=0.64-0.80), in HCC beyond the BCLC stage A (HR=0.60, 95%CI=0.51-0.69), in HCC within the BCLC stage B alone (HR=0.48, 95%CI=0.25-0.90), and in HCC with PVTT (HR=0.78, 95%CI=0.68-0.91). The statistical significance was also confirmed by sensitivity analyses in moderate- and high-quality studies (HR=0.62, 95%CI=0.53-0.71) and in studies published after 2005 (HR=0.59, 95%CI=0.53-0.66). CONCLUSIONS Based on a systematic review and meta-analysis, hepatic resection may be considered in HCC beyond the BCLC stage A. However, given the limitations of study quality, more well-designed randomized controlled trials should be warranted to confirm these findings.
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Affiliation(s)
- Xingshun Qi
- Department of Gastroenterology, General Hospital of Shenyang Military Area, Shenyang, China
| | - Diya Wang
- Department of Occupational and Environmental Health Sciences, Fourth Military Medical University, Xi'an, China
| | - Chunping Su
- Library of Fourth Military Medical University, Xi'an, China
| | - Hongyu Li
- Department of Gastroenterology, General Hospital of Shenyang Military Area, Shenyang, China
| | - Xiaozhong Guo
- Department of Gastroenterology, General Hospital of Shenyang Military Area, Shenyang, China
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Abstract
Liver-related biomarkers have been developed and validated mainly in patients with chronic hepatitis C for the prediction of liver fibrosis or cirrhosis, which is a final pathway of chronic liver injury. They are noninvasive, traceable, and easy-to-use. Biomarkers provide implications related to screening, diagnosis, treatment, and prognosis of chronic hepatitis. For the improvement of performance and coverage, biomarker panels, imaging biomarkers, and even genetic biomarkers have been developed. With the advancement of genomics and proteomics, earlier and more precise prediction is expected in the near future. In this review, multiple biomarker panels for the estimation of the degree of fibrosis in chronic hepatitis C, biomarkers for the screening and diagnosis of hepatitis C, biomarkers for the treatment of hepatitis C, biomarkers for the prediction of complications related to the chronic hepatitis C, and future perspectives will be summarized.
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Affiliation(s)
- Seung Ha Park
- Department of Internal Medicine, Inje University College of Medicine, Busan, South Korea
| | - Chang Seok Bang
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, South Korea
| | - Dong Joon Kim
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, South Korea.
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Ozkan ZG, Poyanli A, Ucar A, Kuyumcu S, Akyuz F, Keskin S, Saglam S, Yilmaz E, Karaca C, Turkmen C. Favorable survival time provided with radioembolization in hepatocellular carcinoma patients with and without portal vein thrombosis. Cancer Biother Radiopharm 2015; 30:132-138. [PMID: 25760644 DOI: 10.1089/cbr.2014.1748] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023] Open
Abstract
PURPOSE Although some algorithms are defined for the treatment of advanced hepatocellular carcinoma (HCC), the expected survival cannot be prolonged as it is intended. Treatment options for this group of patients are limited. Radioembolization with yttrium-90 (Y-90) microspheres is a new treatment modality, which has also been used in advanced HCC patients. In this study, the authors aimed to assess the efficiency of radioembolization with Y-90 microspheres and evaluate prognostic factors that influence the survival in HCC patients. PATIENTS AND METHODS The authors retrospectively evaluated data of 29 HCC patients who had radioembolization with Y-90 resin or glass microspheres between May 2009 and January 2014. Patient survival was evaluated by using the Kaplan-Meier method. Subgroup comparisons in terms of age, sex, prior treatment status before radioembolization, tumor burden, time between HCC diagnosis and radioembolization, alpha fetoprotein (AFP) level before radioembolization, presence of portal vein thrombosis (PVT), hepatopulmonary shunt ratio, extrahepatic disease burden, multifocality, bilaterality, Eastern Cooperative Oncology Group (ECOG), Child-Pugh, and Barcelona Clinic Liver Cancer (BCLC) status were performed to evaluate prognostic factors that affected survival. RESULTS There were 29 HCC patients (mean age: 59.9±12 years) in the patient group. Grade ≤1 and 2 ECOG performance status was present in 19 and 10 patients, respectively. Twenty-six patients were classified as Child A and 3 patients as Child B. According to the BCLC staging system, 18 patients were in stage B and 11 patients were in stage C. PVT was diagnosed in 12 patients. The median follow-up was 15 months. The median overall survival was 17±2.5 months. BCLC disease stage was a significant prognostic variable associated with survival, but other parameters, even the presence of PVT, were found to be not significantly affecting survival. CONCLUSION Radioembolization provides favorable survival time in advanced HCC patients. Even patients who are not eligible for transarterial chemoembolization due to PVT can have radioembolization without a decrease in the median survival time.
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Affiliation(s)
- Zeynep Gozde Ozkan
- 1 Nuclear Medicine Department, Istanbul Medical Faculty, Istanbul University , Istanbul, Turkey
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Bertino G, Demma S, Ardiri A, Proiti M, Malaguarnera G, Bertino N, Malaguarnera M, Malaguarnera M. The immune system in hepatocellular carcinoma and potential new immunotherapeutic strategies. BIOMED RESEARCH INTERNATIONAL 2015; 2015:731469. [PMID: 25893197 PMCID: PMC4393929 DOI: 10.1155/2015/731469] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/25/2014] [Revised: 12/11/2014] [Accepted: 12/12/2014] [Indexed: 02/08/2023]
Abstract
BACKGROUND Hepatocellular carcinoma is a major health problem worldwide and the third most common cause of cancer-related death. HCC treatment decisions are complex and dependent upon tumor staging. Several molecular targeted agents have been evaluated in clinical trials in advanced HCC. Despite of only modest objective response rates according to the Response Evaluation Criteria in Solid Tumors, several studies showed encouraging results in terms of prolongation of the time to progression, disease stabilization, and survival. Cellular immunotherapy would improve the immune state and has potential in enhancing the therapeutic outcome for HCC patients. MATERIALS AND METHODS A search of the literature was made using cancer literature, the PubMed, Scopus, and Web of Science (WOS) database for the following keywords: "hepatocellular carcinoma," "molecular hepatocarcinogenesis," "targeted therapy," "molecular immunological targets," "tumour-associated antigens," "Tregs," "MDSCs," "immunotherapy." DISCUSSION AND CONCLUSION Treatment strategies combining blockade of immunoregulatory cell types such as Tregs and MDSCs and of inhibitory receptors, with vaccine-induced activation of TAA-specific T cells, may be necessary to achieve the most effective therapeutic antitumour activity in HCC. In the future, new therapeutic options will be represented by a blend of immunotherapy-like vaccines and T-cell modulators, supplemented by molecularly targeted inhibitors of tumor signaling pathways.
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Affiliation(s)
- Gaetano Bertino
- Department of Medical and Pediatric Sciences, Hepatology Unit, University of Catania, Policlinic, Via S. Sofia No. 78, 95123 Catania, Italy
| | - Shirin Demma
- Department of Medical and Pediatric Sciences, Hepatology Unit, University of Catania, Policlinic, Via S. Sofia No. 78, 95123 Catania, Italy
| | - Annalisa Ardiri
- Department of Medical and Pediatric Sciences, Hepatology Unit, University of Catania, Policlinic, Via S. Sofia No. 78, 95123 Catania, Italy
| | - Maria Proiti
- Department of Medical and Pediatric Sciences, Hepatology Unit, University of Catania, Policlinic, Via S. Sofia No. 78, 95123 Catania, Italy
| | - Giulia Malaguarnera
- Research Centre “The Great Senescence”, University of Catania, Cannizzaro Hospital, Via Messina No. 829, 95100 Catania, Italy
| | - Nicoletta Bertino
- Faculty of Pharmacy, University of Catania, Viale Andrea Doria No. 6, 95123 Catania, Italy
- Faculty of Pharmacy, University of Catania, University of Catania Policlinic, Via S. Sofia No. 78, 95123 Catania, Italy
| | - Mariano Malaguarnera
- Department of Medical and Pediatric Science, Research Centre “The Great Senescence”, University of Catania, Cannizzaro Hospital, Via Messina No. 829, 95100 Catania, Italy
| | - Michele Malaguarnera
- Research Centre “The Great Senescence”, University of Catania, Cannizzaro Hospital, Via Messina No. 829, 95100 Catania, Italy
- International Ph.D. Program in Neuropharmacology, University of Catania, Cannizzaro Hospital, Via Messina No. 829, 95100 Catania, Italy
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Zhang JW, Li Y, Zeng XC, Zhang T, Fu BS, Yi HM, Zhang Q, Jiang N. miR-630 overexpression in hepatocellular carcinoma tissues is positively correlated with alpha-fetoprotein. Med Sci Monit 2015; 21:667-73. [PMID: 25731670 PMCID: PMC4356187 DOI: 10.12659/msm.892515] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2014] [Accepted: 10/13/2014] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND MicroRNA-630 (miR-630) has been shown to be involved in various human malignancies. However, its role in hepatocellular carcinoma (HCC) remains unknown. MATERIAL AND METHODS TaqMan qRT-PCR assay was performed to detect the expression of miR-630 in 42 pairs of HCC tissues and corresponding noncancerous hepatocellular tissues, and its correlations with clinicopathologic features and serum alpha-fetoprotein (AFP) level of patients were analyzed. RESULTS The present study found that miR-630 expression was significantly increased in HCC tissues and cells compared with their normal counterparts. miR-630 expression level did not significantly chang at stage I but was markedly increased at advanced TNM stage (stage II~III). In addition, the increased expression of miR-630 in tissues of HCC appeared in patients who exhibited elevated serum levels of AFP (>25 ng/ml), but not in those with normal AFP levels (≤25 ng/ml). The miR-630 expression in carcinoma tissues revealed a positive correlation with the levels of serum alpha-fetoprotein (AFP; R2=0.768). CONCLUSIONS These results suggest that miR-630 is associated with tumor progression of hepatocellular carcinoma and may be a potential prognosis indicator.
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Affiliation(s)
- Jian-wen Zhang
- Department of Hepatic Surgery, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Yang Li
- Department of Hepatic Surgery, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Xian-Cheng Zeng
- Department of General Surgery, Zengcheng People’s Hospital, (BoJi-Affiliated Hospital of Sun Yat-Sen University), Zengcheng, Guangdong, China
| | - Tong Zhang
- Department of Hepatic Surgery, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Bin-Sheng Fu
- Department of Hepatic Surgery, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Hui-Min Yi
- Department of Hepatic Surgery, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Qi Zhang
- Department of Hepatic Surgery, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Nan Jiang
- Department of Hepatic Surgery, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
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Liu J, Gao Y, Yang B, Jia X, Zhai D, Li S, Zhang Q, Jing L, Wang Y, Du Z, Wang Y. Overexpression of squamous cell carcinoma antigen 1 is associated with the onset and progression of human hepatocellular carcinoma. Arch Med Res 2015; 46:133-141. [PMID: 25819271 DOI: 10.1016/j.arcmed.2015.03.003] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2014] [Accepted: 03/12/2015] [Indexed: 12/16/2022]
Abstract
BACKGROUND AND AIMS Previous studies indicated Squamous Cell Carcinoma Antigen 1 (SCCA1) may be involved in tumorigenesis and progress of various human malignancies by inhibiting cell apoptosis and promoting cell proliferative activity. The aim of the study was to further investigate SCCA1 expression in different extent of liver diseases and evaluate the clinical significance and prognostic value in HCC. METHODS Eighty nine patient-matched tumors and peritumoral surgical specimens and 56 liver biopsies specimens from 23 patients with chronic hepatitis B (CHB), 19 with dysplastic nodule (DN), and 14 with HCC were enrolled. An additional four normal liver (NL) samples were used as controls. SCCA1 expression in liver tissue was measured by immunochemistry. Another 28 HCC specimens and paired non-tumor tissues were used for SCCA1 detection by Western blot. The prognostic value of SCCA1 expression in HCC was evaluated by the Cox proportional hazards regression model analysis. RESULTS Western blot analysis showed SCCA1 positive rate in HCC was higher than the matched adjacent noncancerous tissues (p <0.001). Immunohistochemistry revealed that SCCA1-positive rate increased gradually from NL, CHB, PNT to DN and HCC (p <0.05). Clinicopathological analysis showed that SCCA1 expression was positively associated with tumor differentiation (p = 0.043) and patients' Child-Pugh score (p = 0.021). The SCCA1-poistive group showed better overall survival than the negative group (p = 0.029). Importantly, SCCA1 expression was an independent prognostic factor for the overall survival of HCC patients (hazard ratio = 3.757, p <0.001). CONCLUSION SCCA1 expression pattern may relate to the progression of chronic liver diseases. Furthermore, our study supports a potential association of negative SCCA1 expression with poor outcome in HCC.
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Affiliation(s)
- Jiao Liu
- Third Central Clinical College of Tianjin Medical University, Tianjin, China
| | - Yingtang Gao
- Key Laboratory of Artificial Cell, Institute for Hepatobiliary Disease, Third Central Hospital of Tianjin, Tianjin, China
| | - Bin Yang
- Key Laboratory of Artificial Cell, Institute for Hepatobiliary Disease, Third Central Hospital of Tianjin, Tianjin, China
| | - Xiaobo Jia
- Third Central Clinical College of Tianjin Medical University, Tianjin, China
| | - Daokuan Zhai
- Department of Science and Education, Third Central Hospital of Tianjin, Tianjin, China
| | - Shilei Li
- Deparment of Hepatobiliary, Shengli Oilfield Central Hospital, Dongying, Shangdong, China
| | - Qin Zhang
- Department of Pathology, Third Central Hospital of Tianjin, Tianjin, China
| | - Li Jing
- Key Laboratory of Artificial Cell, Institute for Hepatobiliary Disease, Third Central Hospital of Tianjin, Tianjin, China
| | - Yajie Wang
- Third Central Clinical College of Tianjin Medical University, Tianjin, China
| | - Zhi Du
- Key Laboratory of Artificial Cell, Institute for Hepatobiliary Disease, Third Central Hospital of Tianjin, Tianjin, China; Department of Hepatobiliary Surgery, Third Central Hospital of Tianjin, Tianjin, China
| | - Yijun Wang
- Department of Hepatobiliary Surgery, Third Central Hospital of Tianjin, Tianjin, China.
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