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Zheng G, Zheng M, Hu P, Zhu Y, Zhang W, Zhang F. Lasso-Based Nomogram for Predicting Early Recurrence Following Radical Resection in Hepatocellular Carcinoma. J Hepatocell Carcinoma 2025; 12:539-552. [PMID: 40099228 PMCID: PMC11911823 DOI: 10.2147/jhc.s510581] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2024] [Accepted: 03/01/2025] [Indexed: 03/19/2025] Open
Abstract
Background Hepatocellular carcinoma (HCC) is a common malignancy with a high recurrence rate following curative resection. This study aimed to identify factors contributing to early recurrence (within 2 years) and develop a Lasso-based nomogram for individualized risk assessment. Methods We conducted a retrospective analysis of 206 hCC patients who underwent curative resection at Taizhou Hospital, Zhejiang Province, from January 2019 to August 2022. Patients were randomly divided into training (n=144) and validation (n=62) cohorts. Lasso regression was used to identify potential recurrence risk factors among 17 candidate predictors. A Cox proportional hazards model was constructed based on variables selected by Lasso. Model performance was assessed using receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA). Results Five independent predictors of early HCC recurrence were identified: age, serum alanine aminotransferase (ALT) levels, cirrhosis, tumor diameter, and microvascular invasion (MVI). The nomogram demonstrated area under the curve (AUC) values for recurrence-free survival (RFS) of 0.828 (95% confidence interval [CI]: 0.753-0.904) at 1 year, 0.799 (95% CI: 0.718-0.880) at 2 years, and 0.742 (95% CI: 0.642-0.842) at 5 years in the training cohort. The corresponding AUCs in the validation cohort were 0.823 (95% CI: 0.686-0.960), 0.804 (95% CI: 0.686-0.922), and 0.857 (95% CI: 0.722-0.992) at 1, 2 and 5 years, respectively. Calibration curves and DCA confirmed the nomogram's high accuracy and clinical utility. Conclusion The Lasso-Cox regression nomogram effectively predicts HCC recurrence within two years post-hepatectomy, providing a valuable tool for personalized postoperative management to improve patient outcomes.
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Affiliation(s)
- Guoqun Zheng
- Department of Hepatopancreatobiliary Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, People’s Republic of China
| | - Minjie Zheng
- Department of Hepatopancreatobiliary Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, People’s Republic of China
| | - Peng Hu
- Department of Hepatopancreatobiliary Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, People’s Republic of China
| | - Yu Zhu
- Department of Hepatopancreatobiliary Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, People’s Republic of China
| | - Wenlong Zhang
- Department of Hepatopancreatobiliary Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, People’s Republic of China
| | - Fabiao Zhang
- Department of Hepatopancreatobiliary Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, People’s Republic of China
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Fu S, Xu Y, Mao Y, He M, Chen Z, Huang S, Li D, Lv Y, Wu J. Hepatic arterial infusion chemotherapy, lenvatinib plus programmed cell death protein-1 inhibitors: A promising treatment approach for high-burden hepatocellular carcinoma. Cancer Med 2024; 13:e7105. [PMID: 38686567 PMCID: PMC11058683 DOI: 10.1002/cam4.7105] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2023] [Revised: 12/18/2023] [Accepted: 03/03/2024] [Indexed: 05/02/2024] Open
Abstract
BACKGROUND Hepatic arterial infusion chemotherapy (HAIC) has demonstrated remarkable local therapeutic efficacy in treating patients with large unresectable hepatocellular carcinoma (HCC). Additionally, the combination of lenvatinib and programmed cell death protein-1 (PD-1) inhibitors has demonstrated promising antitumor effects in unresectable HCC. Therefore, we conducted a retrospective analysis to evaluate the efficacy and safety of combining HAIC with lenvatinib and PD-1 inhibitors as a first-line therapeutic approach in high-burden HCC patients. METHODS We conducted a retrospective analysis on patients diagnosed with high-burden HCC who had major portal vein tumor thrombosis (Vp3 and Vp4) or tumor occupancy exceeding 50% of the liver. These patients received a first-line treatment consisting of HAIC with a combination of 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX), along with lenvatinib and PD-1 inhibitors between November 2020 and June 2023. The primary endpoints of this study included progression-free survival (PFS) and overall survival (OS), while the secondary endpoints were objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events (TRAEs). RESULTS Ninety-one patients were enrolled in this study, with a median PFS of 8.8 months (95% confidence interval [CI]: 5.75-11.78) and a median OS of 14.3 months (95% CI: 11.23-17.31). According to RECIST 1.1 criteria, the ORR was 52.7%, and DCR was 95.6%. According to the mRECIST criteria, the ORR was 72.5%, and the DCR was 96.5%. Among all patients, 86 (94.5%) experienced TRAEs, and there were no instances of treatment-related deaths. CONCLUSION The combination of HAIC-FOLFOX with lenvatinib and PD-1 inhibitors as a first-line therapy has exhibited notable therapeutic efficacy and well-tolerated adverse events among patients with high-burden HCC.
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Affiliation(s)
- Shumin Fu
- Department of Oncology, The Second Affiliated Hospital, Jiangxi Medical CollegeNanchang UniversityNanchangJixangxiChina
| | - Yongkang Xu
- Department of Oncology, The Second Affiliated Hospital, Jiangxi Medical CollegeNanchang UniversityNanchangJixangxiChina
| | - Ye Mao
- Department of Oncology, The Second Affiliated Hospital, Jiangxi Medical CollegeNanchang UniversityNanchangJixangxiChina
| | - Mengting He
- Department of Oncology, The Second Affiliated Hospital, Jiangxi Medical CollegeNanchang UniversityNanchangJixangxiChina
| | - Zhimeng Chen
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Jiangxi Medical CollegeNanchang UniversityNanchangJixangxiChina
| | - Shenglan Huang
- Department of Oncology, The Second Affiliated Hospital, Jiangxi Medical CollegeNanchang UniversityNanchangJixangxiChina
| | - Dan Li
- Department of Oncology, The Second Affiliated Hospital, Jiangxi Medical CollegeNanchang UniversityNanchangJixangxiChina
| | - Yaqin Lv
- Department of Oncology, The Second Affiliated Hospital, Jiangxi Medical CollegeNanchang UniversityNanchangJixangxiChina
| | - Jianbing Wu
- Department of Oncology, The Second Affiliated Hospital, Jiangxi Medical CollegeNanchang UniversityNanchangJixangxiChina
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Hu Z, Yang Z, Wang J, Fu Y, Hu Z, Zhou Z, Chen M, Zhang Y. Survival benefit of neoadjuvant hepatic arterial infusion chemotherapy followed by hepatectomy for hepatocellular carcinoma with portal vein tumor thrombus. Front Pharmacol 2023; 14:1223632. [PMID: 37799969 PMCID: PMC10549930 DOI: 10.3389/fphar.2023.1223632] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Accepted: 09/06/2023] [Indexed: 10/07/2023] Open
Abstract
Background/purpose: The prognosis of hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) is generally poor and hepatectomy is optional for these patients. This study aims to explore the survival benefits of neoadjuvant hepatic arterial infusion chemotherapy (HAIC) for resectable HCC with PVTT. Methods: This retrospective study included 120 resectable HCC patients with PVTT who underwent hepatectomy, from January 2017 to January 2021 at Sun Yat-sen University Cancer Center. Of these patients, the overall survival (OS) and recurrence-free survival (RFS) of 55 patients who received hepatectomy alone (Surgery group) and 65 patients who received neoadjuvant HAIC followed by hepatectomy (HAIC-Surgery group) were compared. Logistic regression analysis was conducted to develop a model predicting the response to neoadjuvant HAIC. Results: The OS rates for the HAIC-Surgery group at 1, 3, and 5 years were 94.9%, 78%, and 66.4%, respectively, compared with 84.6%, 47.6%, and 37.2% in the Surgery group (p < 0.001). The RFS rates were 88.7%, 56.2%, and 38.6% versus 84.9%, 38.3%, and 22.6% (p = 0.002). The subgroup analysis revealed that the survival benefit of neoadjuvant HAIC was limited to patients who responded to it. The logistic model, consisting of AFP and CRP, that predicted the response to neoadjuvant HAIC performed well, with an area under the ROC curve (AUC) of 0.756. Conclusion: Neoadjuvant HAIC followed by hepatectomy is associated with a longer survival outcome than hepatectomy alone for HCC patients with PVTT and the survival benefit is limited to patients who respond to neoadjuvant FOLFOX-HAIC.
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Affiliation(s)
- Zili Hu
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Zhenyun Yang
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Jiongliang Wang
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Yizhen Fu
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Zhiwen Hu
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Zhongguo Zhou
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Minshan Chen
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Yaojun Zhang
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China
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Kaneko S, Tsuchiya K, Yasui Y, Inada K, Kirino S, Yamashita K, Osawa L, Hayakawa Y, Sekiguchi S, Higuchi M, Takaura K, Maeyashiki C, Tamaki N, Takeguchi T, Takeguchi Y, Nagano T, Nakanishi H, Itakura J, Takahashi Y, Himeno Y, Hoshi A, Kurosaki M, Izumi N. Strategy for advanced hepatocellular carcinoma based on liver function and portal vein tumor thrombosis. Hepatol Res 2020; 50:1375-1385. [PMID: 32924266 DOI: 10.1111/hepr.13567] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Revised: 08/06/2020] [Accepted: 08/19/2020] [Indexed: 02/08/2023]
Abstract
AIM Tyrosine kinase inhibitor (TKI) therapy resulted in better prognosis for patients with hepatocellular carcinoma (HCC). However, some cases with Barcelona Clinic Liver Cancer (BCLC) stage C disease still had poor prognosis. This study aimed to investigate prognosis and characteristics of patients with HCC treated with TKI based on liver function and the extent of portal vein tumor thrombosis (PVTT). METHODS Patients receiving TKI therapy (n = 345) were recruited retrospectively. Child-Pugh score and albumin-bilirubin (ALBI) score were used for assessment of liver function. The extent of PVTT was classified from Vp0 to Vp4. Radiotherapy or hepatic arterial infusion chemotherapy were carried out as additional therapy to TKI. The end-point for this analysis was overall survival (OS). RESULTS A total of 291 and 54 patients received sorafenib and lenvatinib as first-line TKI therapy, respectively. The median OS of patients treated with TKI were significantly stratified by ALBI grade (grade 1, 20.1 months; grade 2a, 16.3 months; grades 2b and 3, 9.8 months; P = 0.0003). The classification of PVTT significantly stratified the prognosis of patients treated with TKI (median OS: Vp0, 18.5 months; Vp1/2, 14.4 months; Vp3/4, 5.5 months; P < 0.0001). In the ALBI 2b/3 and Vp3/4 groups, the median OS of patients treated with TKI and additional therapies was significantly longer than those treated with TKI only (9.2 months vs.. 3.6 months; P = 0.0129). CONCLUSION Liver function and PVTT are useful for stratifying prognosis of HCC patients treated with TKI. The applicative classification could lead to appropriate therapy and better prognosis.
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Affiliation(s)
- Shun Kaneko
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Kaoru Tsuchiya
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Yutaka Yasui
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Kento Inada
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Sakura Kirino
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Koji Yamashita
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Leona Osawa
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Yuka Hayakawa
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Shuhei Sekiguchi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Mayu Higuchi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Kenta Takaura
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Chiaki Maeyashiki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Nobuharu Tamaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Takaya Takeguchi
- Department of Radiology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Yuko Takeguchi
- Department of Radiology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Takuya Nagano
- Department of Radiology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Hiroyuki Nakanishi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Jun Itakura
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Yuka Takahashi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Yoshiro Himeno
- Department of Radiology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Akihiko Hoshi
- Department of Radiology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Masayuki Kurosaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Namiki Izumi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
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Hu XG, Shen XY, Nan JN, Kim IG, Yoon JK, Hong SY, Kim MN, Kim BW, Wang HJ. 18F-fluorodeoxyglucose PET/CT as an independent predictor for patients with hepatocellular carcinoma combined with major portal vein tumor thrombus. Ann Surg Treat Res 2020; 99:8-17. [PMID: 32676477 PMCID: PMC7332322 DOI: 10.4174/astr.2020.99.1.8] [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: 12/02/2019] [Revised: 03/07/2020] [Accepted: 04/07/2020] [Indexed: 11/30/2022] Open
Abstract
PURPOSE Hepatocellular carcinoma (HCC) patients with major portal vein tumor thrombosis (mPVTT) complications were generally characterized by extremely poor prognoses. The aim of this study was to explore the role of 18F-fluorodeoxyglucose (18F-FDG) PET/CT imaging in predicting HCC complicated by mPVTT. METHODS Five hundred one HCC patients received surgery in our hospital during November 2008 to December 2014, among which 32 patients (6.4%) were diagnosed as HCC complicated by mPVTT. Six cases were excluded for reasons of complex medical conditions, including 2 cases of salvage liver transplantation, 2 cases of re-resection, 1 case of mPVTT combined with inferior vina cava tumor thrombosis, and 1 case of residual portal vein tumor thrombosis. Ultimately, 26 cases were enrolled in this study. The maximal tumor standardized uptake value (SUVmax) was identified as a predictive factor and detected. The univariate and multivariate regression analyses were performed to identify the prognostic factors for recurrence-free survival (RFS) and overall survival (OS) of HCC patients complicated by mPVTT. RESULTS Our results showed that the median OS was 16 months. The 1-, 3-, and 5-year cumulative OS was 55.6%, 31.7%, and 31.7%, respectively. The multivariate regression analysis revealed that SUVmax ≥ 4.65 was the only independent risk factor for RFS and OS. CONCLUSION SUVmax was an independent predictor for RFS and OS of patients suffering from both HCC and mPVTT. L ow SUVmax could serve as an effective factor for selecting candidates with low recurrence risks and for helping with improving patient survival after surgical resection.
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Affiliation(s)
- Xu-Guang Hu
- Division of Hepatobiliary Surgery and Intervention, Department of Surgery, Jiangxi Cancer Hospital, Nan Chang, China
| | - Xue-Yin Shen
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Ajou University School of Medicine, Suwon, Korea
| | - Jin-Niang Nan
- Department of Clinical Medicine, Jiangxi Health Career College of China, Nan Chang, China
| | - In-Gyu Kim
- Health Insurance Review and Assessment Service, Seoul, Korea
| | - Joon-Kee Yoon
- Department of Nuclear Medicine and Molecular Imaging, Ajou University School of Medicine, Suwon, Korea
| | - Sung-Yeon Hong
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Ajou University School of Medicine, Suwon, Korea
| | - Mi-Na Kim
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Ajou University School of Medicine, Suwon, Korea
| | - Bong-Wan Kim
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Ajou University School of Medicine, Suwon, Korea
| | - Hee-Jung Wang
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Ajou University School of Medicine, Suwon, Korea
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Cheng E, Hung P, Wang SY. Geographic Variations of Potentially Curative Treatments for Hepatocellular Carcinoma in the United States: A SEER-Medicare Study. J Natl Compr Canc Netw 2020; 18:729-736. [DOI: 10.6004/jnccn.2020.7529] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2019] [Accepted: 01/06/2020] [Indexed: 11/17/2022]
Abstract
Background: Transplantation, surgical resection, radiofrequency ablation, and percutaneous ethanol injection are generally considered potentially curative treatments for patients with hepatocellular carcinoma (HCC). With the increasing incidence of HCC, it is critical to investigate geographic variations in curative treatments and their associations with survival among patients. Methods: A total of 6,782 patients with HCC during 2004 to 2011 were identified in the SEER-Medicare linked database and placed in quartiles based on the proportions undergoing potentially curative treatments per hospital referral region (HRR). Hierarchical Cox proportional hazards models were used to examine the association between regional potentially curative treatment patterns and survival across quartiles. Results: An average of 16.9% of patients with HCC underwent potentially curative treatments during 2004 to 2011, varying substantially from 0% to 34.5% across HRRs. Compared with patients residing in the lowest-quartile regions, those in the highest-quartile regions were more likely to be of other races (vs white or black), be infected with hepatitis B virus, and have more comorbidities. The 5-year survival was 4.7% in the lowest-quartile regions and 11.4% in the highest-quartile regions (P<.001). After controlling for confounders, patients in the highest-quartile regions had a lower risk of mortality (adjusted hazard ratio, 0.78; 95% CI, 0.72–0.85). Conclusions: Patients with HCC who resided in HRRs with higher proportions of potentially curative treatments had better survival. Given its proven survival benefits, prompt clinical and policy actions are needed to reduce variations in treatment utilization.
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Affiliation(s)
- En Cheng
- 1Department of Chronic Disease Epidemiology, School of Public Health, Yale University, New Haven, Connecticut
| | - Peiyin Hung
- 2Department of Health Services Policy and Management, Arnold School of Public Health, University of South Carolina, and
- 3Rural and Minority Health Research Center, Columbia, South Carolina; and
| | - Shi-Yi Wang
- 1Department of Chronic Disease Epidemiology, School of Public Health, Yale University, New Haven, Connecticut
- 4Cancer Outcomes, Public Policy, and Effectiveness Research Center, Yale Cancer Center, New Haven, Connecticut
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Yuan WH, Li AFY, Hsu HC, Hu YS, Lee RC. Initial clinical radiological findings and staging to predict prognosis of primary hepatic angiosarcoma: A retrospective analysis. PLoS One 2019; 14:e0225043. [PMID: 31710641 PMCID: PMC6844487 DOI: 10.1371/journal.pone.0225043] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2019] [Accepted: 10/27/2019] [Indexed: 12/13/2022] Open
Abstract
OBJECTIVE Primary hepatic angiosarcoma (PHA) is extremely rare and most patients die within 12 months of diagnosis. The object of the study is to determine the association of initial clinical-radiological features and staging with outcomes in patients with PHA. METHODS The medical records of adult patients with PHA were retrieved from an electronic medical record database and a pathology database and retrospectively reviewed. During 10 years, 22 eligible patients were included. Data extracted focused on the information before the first formal treatment with a pathological proof, including demographic characteristics, medical history, laboratory data, preliminary images, histopathological records, treatment, and follow-up survival period. Two radiologists blindly re-analyzed preliminary images of all 22 patients together and recorded tumor features and imaging stage based on the American Joint Committee on Cancer (AJCC) 8th edition tumor-node-metastasis (TNM) Staging System for hepatocellular carcinoma. A radiologist compiled the initial clinical data and preliminary image stage to analyze the association with patients' survival outcome. RESULTS Higher aspartate aminotransferase (AST), higher total bilirubin (TB), lower albumin (ALB), longer prothrombin time (PT) and lower platelet count of serum relative to the normal reference range were more common in patients who survived ≤ 90 days (all P < 0.05). Overall survival was much better in patients with single PHA than in those with other tumor patterns of multiple PHA (all P < 0.05). Overall survival determined by preliminary imaging showed significant differences between stage I and stage III (P = 0.044), stage I and stage IV (P = 0.011), and stage III and IV (P = 0.047). No patients were at stage II. CONCLUSIONS Initial serum levels of ALT, TB, ALB, and PT, platelet count, single mass in liver, and preliminary imaging staging could help predict survival outcomes of patients with PHA.
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Affiliation(s)
- Wei-Hsin Yuan
- Division of Radiology, Taipei Municipal Gan-Dau Hospital (managed by Taipei Veterans General Hospital), Taipei, Taiwan, Republic of China
- School of Medicine, National Yang Ming University, Taipei, Taiwan, Republic of China
- Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China
- * E-mail: , (WHY); (RCL)
| | - Anna Fen-Yau Li
- School of Medicine, National Yang Ming University, Taipei, Taiwan, Republic of China
- Department of Pathology, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China
| | - Hui-Chen Hsu
- Department of Medical Imaging, Taiwan Adventist Hospital, Taipei, Taiwan, Republic of China
| | - Yong-Sin Hu
- School of Medicine, National Yang Ming University, Taipei, Taiwan, Republic of China
- Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China
| | - Rheun-Chuan Lee
- School of Medicine, National Yang Ming University, Taipei, Taiwan, Republic of China
- Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China
- * E-mail: , (WHY); (RCL)
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Lee BH, Lee DS, Cho CW, Yun SS. Role and limitation of neoadjuvant hepatic arterial infusion chemotherapy in advanced hepatocelluar carcinoma patients with Child-Pugh class A. World J Surg Oncol 2019; 17:143. [PMID: 31416447 PMCID: PMC6694530 DOI: 10.1186/s12957-019-1685-6] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2019] [Accepted: 08/06/2019] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Patients with advanced hepatocellular carcinoma (HCC) have a poor oncologic outcome. In this study, we evaluated the role and limitation of neoadjuvant hepatic arterial infusion chemotherapy (HAIC) in advanced HCC patients with Child-Pugh class A and the efficacy of liver resection subsequent to downstaging after neoadjuvant HAIC. METHODS In the present retrospective study, 103 patients with advanced HCC, who underwent neoadjuvant HAIC from April 2003 to March 2015 were analyzed. Response to HAIC was evaluated by dividing time period into after 3 cycles and after 6 cycles, each defined as early and late period. Liver resection after neoadjuvant HAIC was offered in patients who were considered as possible candidates for curative resection with tumor-free margin as well as sufficient future liver remnant volume. RESULTS The median survival time (MST) in all patients was 14 ± 1.7 months. Response rate and disease control rate were 36.3% (37) and 81.4% (83) in early period, respectively, and 26.4% (14) and 47.2% (25), in late period, respectively (P = 0.028). Twelve patients (11.7%) underwent liver resection after neoadjuvant HAIC and the MST was 37 ± 6.6 months. One-, 3-, and 5-year recurrence-free survival after liver resection were 58.3%, 36.5%, and 24.3% respectively. Liver resection was identified as the only independent prognostic factor that associated with overall survival in multivariate analysis (P = 0.002) CONCLUSION: HAIC could be further alternative for the treatment of advanced HCC in patients with good liver function. If liver resection is possible after neoadjuvant HAIC, liver resection would provide better outcomes than HAIC alone.
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Affiliation(s)
- Beom-Hui Lee
- Department of Surgery, College of Medicine, Yeungnam University, 170 Hyeonchungno, Nam-gu, Daegu, 42415, Republic of Korea
| | - Dong-Shik Lee
- Department of Surgery, College of Medicine, Yeungnam University, 170 Hyeonchungno, Nam-gu, Daegu, 42415, Republic of Korea
| | - Chan Woo Cho
- Department of Surgery, College of Medicine, Yeungnam University, 170 Hyeonchungno, Nam-gu, Daegu, 42415, Republic of Korea
| | - Sung-Su Yun
- Department of Surgery, College of Medicine, Yeungnam University, 170 Hyeonchungno, Nam-gu, Daegu, 42415, Republic of Korea.
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Mähringer-Kunz A, Steinle V, Düber C, Weinmann A, Koch S, Schmidtmann I, Schotten S, Hinrichs JB, Graafen D, Pinto Dos Santos D, Galle PR, Kloeckner R. Extent of portal vein tumour thrombosis in patients with hepatocellular carcinoma: The more, the worse? Liver Int 2019; 39:324-331. [PMID: 30318826 DOI: 10.1111/liv.13988] [Citation(s) in RCA: 51] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2018] [Revised: 10/03/2018] [Accepted: 10/04/2018] [Indexed: 02/13/2023]
Abstract
BACKGROUND & AIMS Portal vein tumour thrombosis (PVTT) has a significant impact on the prognosis of patients with hepatocellular carcinoma (HCC). The degree of PVTT varies from sub-/segmental invasion to complete occlusion of the main trunk. Aim of this study was to evaluate whether the degree of PVTT correlates with prognosis. METHODS A total of 1317 patients with HCC treated at our tertiary referral centre between January 2005 and December 2016 were included. PVTT was diagnosed by contrast-enhanced computed tomography or magnetic resonance imaging. The extent of PVTT was documented according to the Liver Cancer Study Group of Japan classification: Vp0 = no PVTT, Vp1 = segmental portal vein invasion, Vp2 = right anterior/posterior portal vein, Vp3 = right/left portal vein and Vp4 = main trunk. Median overall survival (OS) was calculated for each group. RESULTS Portal vein tumour thrombosis was present in 484 (36.8%) patients. Median OS without PVTT was 35.7 months, significantly longer than in patients with PVTT (7.2 months, P < 0.001). The patients with PVTT were subclassified as follows: 103 Vp1, 87 Vp2, 143 Vp3 and 151 Vp4. The corresponding median OS yielded 14.6, 9.4, 5.8 and 4.8 months for Vp1-Vp4, respectively (P < 0.001). CONCLUSIONS Portal vein tumour thrombosis in patients with HCC is associated with a dismal prognosis. The results indicate an association between the extent of PVTT and OS. However, the extent of PVTT is not that decisive, as even minor PVTT leads to a very poor prognosis. Therefore, meticulous evaluation of cross-sectional imaging is crucial for the clinical management of patients with HCC.
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Affiliation(s)
- Aline Mähringer-Kunz
- Department of Diagnostic and Interventional Radiology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Verena Steinle
- Department of Diagnostic and Interventional Radiology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Christoph Düber
- Department of Diagnostic and Interventional Radiology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Arndt Weinmann
- Department of Internal Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.,Clinical Registry Unit (CRU), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Sandra Koch
- Clinical Registry Unit (CRU), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Irene Schmidtmann
- Institute of Medical Biostatistics, Epidemiology and Informatics, Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Sebastian Schotten
- Department of Diagnostic and Interventional Radiology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Jan B Hinrichs
- Department of Interventional and Diagnostic Radiology, Hannover Medical School, Hannover, Germany
| | - Dirk Graafen
- Department of Diagnostic and Interventional Radiology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | | | - Peter R Galle
- Department of Internal Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Roman Kloeckner
- Department of Diagnostic and Interventional Radiology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
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10
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Hai S, Hatano E, Okada T, Uyama N, Suzumura K, Fujimoto J. Is Noncurative Hepatic Resection Justified for Advanced Hepatocellular Carcinoma? Am Surg 2018. [DOI: 10.1177/000313481808401241] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
It has been obscure whether or not noncurative hepatic resection (Hx) has a favorable impact on the clinical course in patients with advanced hepatocellular carcinoma (HCC). The aim of this study is to clarify the significance of noncurative Hx for advanced HCC. Among 666 consecutive patients undergoing Hx for HCC in our department, 79 patients underwent noncurative Hx. These patients were classified as Group A (presence of macrovascular invasion [MVI]; n = 29), Group B (residual tumors in the remnant liver; n = 37), Group C (residual tumors in the remnant liver with MVI; n = 7), or Group D (residual tumors in the remnant liver with distant metastasis [with or without MVI]; n = 6). The three-year survival rates were 49.6 per cent in Group A, 30.3 per cent in Group B, 14.3 per cent in Group C, and 0.0 per cent in Group D, respectively (Groups A and B vs Group D, P < 0.05). Moreover, the survival rate was significantly higher in patients with ≤3 tumors than in those with ≥4 tumors ( P < 0.05), when Group B was divided into subgroups according to the number of residual tumors in the remnant liver. In conclusion, noncurative Hx might be acceptable for advanced HCC with MVI or ≤3 residual tumors in the remnant liver.
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Affiliation(s)
- Seikan Hai
- Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan
| | - Etsuro Hatano
- Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan
| | - Toshihiro Okada
- Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan
| | - Naoki Uyama
- Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan
| | - Kazuhiro Suzumura
- Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan
| | - Jiro Fujimoto
- Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan
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11
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Kotewall CN, Cheung TT. Optimizing hepatectomy for hepatocellular carcinoma in Asia-patient selection and special considerations. Transl Gastroenterol Hepatol 2018; 3:75. [PMID: 30505962 DOI: 10.21037/tgh.2018.09.09] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2018] [Accepted: 09/05/2018] [Indexed: 12/12/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is a common affliction in Asia. The treatment of HCC depends on the tumor status as well as the underlying liver function. Resection is the cornerstone of surgical management of HCC. For those unfit to undergo resection, local ablative therapy is a viable alternative. For patients with multiple small unresectable HCCs, liver transplantation offers another option, having the simultaneous benefit of removing the cancer in addition to replacing the pre-malignant and cirrhotic liver together. However, the paucity of liver grafts limits the applicability of this operation. In assessing for the appropriate treatment, the traditional TNM staging is not widely applied to HCC. Conventionally, doctors in the West have relied on the Barcelona staging system. Asian surgeons, on the other hand, have long adopted a more aggressive approach for their patients. Borne out of the need for a system which better suited Asian patients, the Hong Kong guidelines have been established. For the surgical resection of HCC, considerations must take into account issues regarding the tumor, the underlying liver and the patient. For the tumor, the size, the presence vascular invasion and presence of extra-hepatic metastasis will determine operability. Another important issue is the liver function and, by extension, the estimated residual liver volume after resection. Thirdly, patient factors i.e., fitness to undergo general anesthesia must be properly assessed. With improved surgical technique and better patient selection, peri-operative morbidity and long-term survival results after operation have improved drastically over the past decades.
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Affiliation(s)
| | - Tan To Cheung
- Department of Surgery, The University of Hong Kong, Hong Kong, China
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12
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Koh YX, Tan HL, Lye WK, Kam JH, Chiow AKH, Tan SS, Choo SP, Chung AYF, Goh BKP. Systematic review of the outcomes of surgical resection for intermediate and advanced Barcelona Clinic Liver Cancer stage hepatocellular carcinoma: A critical appraisal of the evidence. World J Hepatol 2018; 10:433-447. [PMID: 29988922 PMCID: PMC6033716 DOI: 10.4254/wjh.v10.i6.433] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2017] [Revised: 02/10/2018] [Accepted: 03/03/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To perform a systematic review to determine the survival outcomes after curative resection of intermediate and advanced hepatocellular carcinomas (HCC). METHODS A systematic review of the published literature was performed using the PubMed database from 1st January 1999 to 31st Dec 2014 to identify studies that reported outcomes of liver resection as the primary curative treatment for Barcelona Clinic Liver Cancer (BCLC) stage B or C HCC. The primary end point was to determine the overall survival (OS) and disease free survival (DFS) of liver resection of HCC in BCLC stage B or C in patients with adequate liver reserve (i.e., Child's A or B status). The secondary end points were to assess the morbidity and mortality of liver resection in large HCC (defined as lesions larger than 10 cm in diameter) and to compare the OS and DFS after surgical resection of solitary vs multifocal HCC. RESULTS We identified 74 articles which met the inclusion criteria and were analyzed in this systematic review. Analysis of the resection outcomes of the included studies were grouped according to (1) BCLC stage B or C HCC, (2) Size of HCC and (3) multifocal tumors. The median 5-year OS of BCLC stage B was 38.7% (range 10.0-57.0); while the median 5-year OS of BCLC stage C was 20.0% (range 0.0-42.0). The collective median 5-year OS of both stages was 27.9% (0.0-57.0). In examining the morbidity and mortality following liver resection in large HCC, the pooled RR for morbidity [RR (95%CI) = 1.00 (0.76-1.31)] and mortality [RR (95%CI) = 1.15 (0.73-1.80)] were not significant. Within the spectrum of BCLC B and C lesions, tumors greater than 10 cm were reported to have median 5-year OS of 33.0% and multifocal lesions 54.0%. CONCLUSION Indication for surgical resection should be extended to BCLC stage B lesions in selected patients. Further studies are needed to stratify stage C lesions for resection.
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Affiliation(s)
- Ye Xin Koh
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore 169608, Singapore.
| | - Hwee Leong Tan
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore 169608, Singapore
| | - Weng Kit Lye
- Center for Quantitative Medicine, Duke-NUS Graduate Medical School, Singapore 169857, Singapore
| | - Juinn Huar Kam
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore 169608, Singapore
| | - Adrian Kah Heng Chiow
- Department of General Surgery, Hepatopancreatobiliary Service, Changi General Hospital, Singapore 529889, Singapore
| | - Siong San Tan
- Department of General Surgery, Hepatopancreatobiliary Service, Changi General Hospital, Singapore 529889, Singapore
| | - Su Pin Choo
- Department of Medical Oncology, National Cancer Centre Singapore, Singapore 169610, Singapore
| | - Alexander Yaw Fui Chung
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore 169608, Singapore
| | - Brian Kim Poh Goh
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore 169608, Singapore
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13
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Burt AD, Alves V, Bedossa P, Clouston A, Guido M, Hübscher S, Kakar S, Ng I, Park YN, Reeves H, Wyatt J, Yeh MM, Ellis DW. Data set for the reporting of intrahepatic cholangiocarcinoma, perihilar cholangiocarcinoma and hepatocellular carcinoma: recommendations from the International Collaboration on Cancer Reporting (ICCR). Histopathology 2018; 73:369-385. [DOI: 10.1111/his.13520] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
- Alastair D Burt
- Faculty of Health and Medical Sciences; University of Adelaide; Adelaide Australia
| | - Venâncio Alves
- Department of Pathology; University of São Paulo School of Medicine; São Paulo Brazil
| | - Pierre Bedossa
- Pathology Department; AP-HP; Beaujon Hospital; Clichy France
- Centre de Recherche Bichat-Beaujon; University Paris-Diderot; Paris France
| | - Andrew Clouston
- Envoi Specialist Pathologists; Brisbane Queensland Australia
| | - Maria Guido
- Surgical Pathology and Cytopathology Unit; Department of Medicine-DIMED; University of Padova; Padova Italy
| | - Stefan Hübscher
- Department of Cellular Pathology; Institute of Immunology and Immunotherapy; University of Birmingham; Queen Elizabeth Hospital; Birmingham UK
| | | | - Irene Ng
- Department of Pathology; State Key Laboratory for Liver Research; The University of Hong Kong; Hong Kong Hong Kong
| | - Young N Park
- Department of Pathology Yonsei; Univesity College of Medicine Seodaemun-gu; Seoul Korea
| | - Helen Reeves
- Northern Institute for Cancer Research, Newcastle University; Newcastle upon Tyne UK
| | - Judith Wyatt
- Department of Histopathology; St James University Hospital; Leeds UK
| | - Matthew M Yeh
- Department of Pathology; University of Washington School of Medicine; Seattle WA USA
| | - David W Ellis
- Clinpath Laboratories; Kent Town South Australia Australia
- ICCR Steering Group Representative; Adelaide Australia
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14
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Tian MX, He WJ, Liu WR, Yin JC, Jin L, Tang Z, Jiang XF, Wang H, Zhou PY, Tao CY, Ding ZB, Peng YF, Dai Z, Qiu SJ, Zhou J, Fan J, Shi YH. A Novel Risk prediction Model for Patients with Combined Hepatocellular-Cholangiocarcinoma. J Cancer 2018; 9:1025-1032. [PMID: 29581782 PMCID: PMC5868170 DOI: 10.7150/jca.23229] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2017] [Accepted: 01/28/2018] [Indexed: 12/20/2022] Open
Abstract
Backgrounds: Regarding the difficulty of CHC diagnosis and potential adverse outcomes or misuse of clinical therapies, an increasing number of patients have undergone liver transplantation, transcatheter arterial chemoembolization (TACE) or other treatments. Objective: To construct a convenient and reliable risk prediction model for identifying high-risk individuals with combined hepatocellular-cholangiocarcinoma (CHC). Methods: 3369 patients who underwent surgical resection for liver cancer at Zhongshan Hospital were enrolled in this study. The epidemiological and clinical characteristics of the patients were collected at the time of tumor diagnosis. Variables (P <0.25 in the univariate analyses) were evaluated using backward stepwise method. A receiver operating characteristic (ROC) curve was used to assess model discrimination. Calibration was performed using the Hosmer-Lemeshow test and a calibration curve. Internal validation was performed using a bootstrapping approach. Results: Among the entire study population, 250 patients (7.42%) were pathologically defined with CHC. Age, HBcAb, red blood cells (RBC), blood urea nitrogen (BUN), AFP, CEA and portal vein tumor thrombus (PVTT) were included in the final risk prediction model (area under the curve, 0.69; 95% confidence interval, 0.51-0.77). Bootstrapping validation presented negligible optimism. When the risk threshold of the prediction model was set at 20%, 2.73% of the patients diagnosed with liver cancer would be diagnosed definitely, which could identify CHC patients with 12.40% sensitivity, 98.04% specificity, and a positive predictive value of 33.70%. Conclusions: Herein, the study established a risk prediction model which incorporates the clinical risk predictors and CT/MRI-presented PVTT status that could be adopted to facilitate the diagnosis of CHC patients preoperatively.
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Affiliation(s)
- Meng-Xin Tian
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China
| | - Wen-Jun He
- Department of Medical Statistic and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Wei-Ren Liu
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China
| | - Jia-Cheng Yin
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China
| | - Lei Jin
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China
| | - Zheng Tang
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China
| | - Xi-Fei Jiang
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China
| | - Han Wang
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China
| | - Pei-Yun Zhou
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China
| | - Chen-Yang Tao
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China
| | - Zhen-Bin Ding
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China
| | - Yuan-Fei Peng
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China
| | - Zhi Dai
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China
| | - Shuang-Jian Qiu
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China
| | - Jian Zhou
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China.,Institutes of Biomedical Sciences, Fudan University, Shanghai, People's Republic of China
| | - Jia Fan
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China.,Institutes of Biomedical Sciences, Fudan University, Shanghai, People's Republic of China
| | - Ying-Hong Shi
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China
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15
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Zhang YF, Le Y, Wei W, Zou RH, Wang JH, OuYang HY, Xiao CZ, Zhong XP, Shi M, Guo RP. Optimal surgical strategy for hepatocellular carcinoma with portal vein tumor thrombus: a propensity score analysis. Oncotarget 2018; 7:38845-38856. [PMID: 27072577 PMCID: PMC5122434 DOI: 10.18632/oncotarget.8642] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2015] [Accepted: 03/29/2016] [Indexed: 12/13/2022] Open
Abstract
OBJECTIVES The optimal surgical resection method for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) that maximizes both safety and long-term outcome has not yet been determined. The aim of this study was to compare the clinical outcomes following peeling off versus en bloc resection for PVTT. METHODS From 2005 to 2012, 252 patients with HCC and type I/II PVTT who underwent hepatic resection were divided into two groups according to whether they received en bloc resection (n = 113) or peeling off resection (n = 139). The clinical outcomes were compared before and after propensity score matching. RESULTS The propensity model matched 113 patients with en bloc resection for further analyses. After matching, overall survival (OS) and disease-free survival (DFS) rates were significantly increased in the en bloc group compared with the peeling off group (p = 0.011 and p = 0.015). A multivariate analysis indicated that en bloc resection independently improved both OS and DFS (HR = 1.471, 95% CI: 1.071-2.018, p = 0.017 and HR = 1.415, 95% CI: 1.068-1.874, P=0.016). The adverse events were not significantly different between the two groups. However, the peeling off group showed a significantly increased recurrence rate of vascular invasion compared with the en bloc group (23.9% vs. 9.7%, p = 0.005). Similar results were also demonstrated prior to the matched analysis. CONCLUSIONS An en bloc resection is safe and confers a survival advantage compared with a peeling off resection in HCC patients with PVTT; thus, en bloc resection should be recommended as a standard treatment for these patients when possible.
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Affiliation(s)
- Yong-Fa Zhang
- Department of Hepatobiliary Oncology of Sun Yat-sen University Cancer Center, Guangzhou, P.R. China.,State Key Laboratory of Oncology in South China, Guangzhou, P.R. China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, P.R. China
| | - Yong Le
- Department of Hepatobiliary Oncology of Sun Yat-sen University Cancer Center, Guangzhou, P.R. China.,State Key Laboratory of Oncology in South China, Guangzhou, P.R. China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, P.R. China
| | - Wei Wei
- Department of Hepatobiliary Oncology of Sun Yat-sen University Cancer Center, Guangzhou, P.R. China.,State Key Laboratory of Oncology in South China, Guangzhou, P.R. China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, P.R. China
| | - Ru-Hai Zou
- Department of Hepatobiliary Oncology of Sun Yat-sen University Cancer Center, Guangzhou, P.R. China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, P.R. China.,Department of Ultrasonography of Sun Yat-sen University Cancer Center, Guangzhou, P.R. China
| | - Jia-Hong Wang
- Department of Hepatobiliary Oncology of Sun Yat-sen University Cancer Center, Guangzhou, P.R. China.,State Key Laboratory of Oncology in South China, Guangzhou, P.R. China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, P.R. China
| | - Han-Yue OuYang
- Department of Hepatobiliary Oncology of Sun Yat-sen University Cancer Center, Guangzhou, P.R. China.,State Key Laboratory of Oncology in South China, Guangzhou, P.R. China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, P.R. China
| | - Cheng-Zuo Xiao
- Department of General surgery, Shenzhen Shajing Affiliated Hospital of Guangzhou Medical University, Shenzhen, P.R. China
| | - Xiao-Ping Zhong
- Department of Hepatobiliary Oncology of Sun Yat-sen University Cancer Center, Guangzhou, P.R. China.,State Key Laboratory of Oncology in South China, Guangzhou, P.R. China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, P.R. China
| | - Ming Shi
- Department of Hepatobiliary Oncology of Sun Yat-sen University Cancer Center, Guangzhou, P.R. China.,State Key Laboratory of Oncology in South China, Guangzhou, P.R. China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, P.R. China
| | - Rong-Ping Guo
- Department of Hepatobiliary Oncology of Sun Yat-sen University Cancer Center, Guangzhou, P.R. China.,State Key Laboratory of Oncology in South China, Guangzhou, P.R. China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, P.R. China
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16
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Hepatectomy after down-staging of hepatocellular carcinoma with portal vein tumor thrombus using chemoradiotherapy: A retrospective cohort study. Int J Surg 2017; 44:223-228. [DOI: 10.1016/j.ijsu.2017.06.082] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2017] [Accepted: 06/27/2017] [Indexed: 12/15/2022]
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17
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Ye JZ, Wang YY, Bai T, Chen J, Xiang BD, Wu FX, Li LQ. Surgical resection for hepatocellular carcinoma with portal vein tumor thrombus in the Asia-Pacific region beyond the Barcelona Clinic Liver Cancer treatment algorithms: a review and update. Oncotarget 2017; 8:93258-93278. [PMID: 29190996 PMCID: PMC5696262 DOI: 10.18632/oncotarget.18735] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2017] [Accepted: 04/25/2017] [Indexed: 01/27/2023] Open
Abstract
Portal vein tumor thrombus (PVTT) usually worsens prognosis of hepatocellular carcinoma (HCC), as characterized by aggressive disease progression, impaired liver function and tolerance to treatment. Conventionally, the European Association for the Study of the Liver (EASL) and the American Association for the Study of Liver Diseases (AASLD) accepted the Barcelona Clinical Liver Cancer (BCLC) treatment algorithms, identifying PVTT as an absolute contra-indication of surgical resection for HCC. HCC-PVTT patients are offered sorafenib as the standard treatment. Evidently, SHARP and Asia-Pacific trials demonstrated that sorafenib only improves overall survival by approximately 3 months in patients with advanced HCC. Besides, BCLC treatment algorithm does not provide different therapeutic recommendations for different degree of PVTT, and only supports single treatment option for each stage of HCC rather than a combination of comprehensive treatments, which limited individual and best care for every HCC-PVTT patients. In the past few years, many surgeons do not restrict surgical resection to HCC with PVTT. There have been new reports demonstrated that surgical treatment is feasible for selected HCC-PVTT patients with resectable tumor and moderate liver function to prolong survival period and elevate life quality as long as PVTT limited to the first-order branch, whereas non-surgical treatments fail to provide comparable therapeutic effects. At present, guidelines on HCC management from mainland China, Japan, and Hong Kong have been updated and a consensus of Asia-Pacific experts has established that portal venous invasion is not an absolute contradiction of surgical resection for HCC. This review summarized the emerging data on surgical resection for HCC-PVTT patients beyond the BCLC treatment algorithms and discussed recent therapeutic conceptualchanges in the Asia-Pacific region.
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Affiliation(s)
- Jia-Zhou Ye
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, PR China
| | - Yan-Yan Wang
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, PR China
| | - Tao Bai
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, PR China
| | - Jie Chen
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, PR China
| | - Bang-De Xiang
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, PR China
| | - Fei-Xiang Wu
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, PR China
| | - Le-Qun Li
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, PR China
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18
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Chok KS, Ng KK, Cheung TT, Chan AC, Chan SC, Lo CM. Resection of T4 hepatocellular carcinomas with adjacent structures, is it justified? Hepatobiliary Pancreat Dis Int 2017; 16:52-57. [PMID: 28119259 DOI: 10.1016/s1499-3872(16)60172-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND T4 hepatocellular carcinoma (HCC) with invasion to adjacent structure(s) may require resection of not only the tumor but also the invaded structure(s). This study aims to assess whether such combined resection for T4 HCC is justifiable. METHODS Adult patients with T4 HCC were divided into three groups. Group 1: tumors and invaded adjacent structures were resected together if histopathologically confirmed tumor invasion; group 2: same as group 1 but histopathologically confirmed tumor adhesion; group 3: tumor resection only. Group comparisons were made. RESULTS Totally 144 patients were included in the study. There were 71, 14 and 59 patients in groups 1, 2 and 3, respectively. The groups were comparable in demographics, complication and survival. Ten hospital deaths occurred (5, 0 and 5 in groups 1, 2 and 3, respectively; P=0.533). The 5-year overall survival (hospital mortality excluded) was 17.8% in group 1, 14.3% in group 2, and 28.9% in group 3 (P=0.191). The 5-year disease-free survival was 10.4% in group 1 and 14.5% in group 3 (no data for group 2 yet) (P=0.565). On multivariate analysis, macrovascular invasion and poor differentiation were risk factors for survival whereas combined resection did not impact patients' survival. CONCLUSIONS Combined resection achieved survival outcomes similar to tumor resection only. Patients with tumor invasion and those with tumor adhesion had comparable survival after combined resection. At centers with the required expertise, combined resection should be attempted to treat T4 HCCs with clinically suspected invasion of adjacent structures.
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Affiliation(s)
- Kenneth Sh Chok
- Department of Surgery, The University of Hong Kong, 102 Pok Fu Lam Road, Hong Kong, China.
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Kokudo T, Hasegawa K, Matsuyama Y, Takayama T, Izumi N, Kadoya M, Kudo M, Ku Y, Sakamoto M, Nakashima O, Kaneko S, Kokudo N. Survival benefit of liver resection for hepatocellular carcinoma associated with portal vein invasion. J Hepatol 2016; 65:938-943. [PMID: 27266618 DOI: 10.1016/j.jhep.2016.05.044] [Citation(s) in RCA: 361] [Impact Index Per Article: 40.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2016] [Revised: 05/20/2016] [Accepted: 05/30/2016] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS The presence of portal vein tumor thrombosis (PVTT) in patients with hepatocellular carcinoma (HCC) is regarded as indicating an advanced stage, and liver resection (LR) is not recommended. The aim of this study was to evaluate the survival benefit of LR for HCC patients with PVTT through the analysis of the data from a Japanese nationwide survey. METHODS We analyzed data for 6474 HCC patients with PVTT registered between 2000 and 2007. Of these patients, 2093 patients who underwent LR and 4381 patients who received other treatments were compared. The propensity scores were calculated and we successfully matched 1058 patients (66.1% of the LR group). RESULTS In the Child-Pugh A patients, the median survival time (MST) in the LR group was 1.77years longer than that in the non-LR group (2.87years vs. 1.10years; p<0.001) and 0.88years longer than that in the non-LR group (2.45years vs. 1.57years; p<0.001) in a propensity score-matched cohort. A subgroup analysis revealed that LR provides a survival benefit regardless of age, etiology of HCC, tumor marker elevation, and tumor number. The survival benefit was not statistically significant only in patients with PVTT invading the main trunk or contralateral branch. In the LR group, the postoperative 90-day mortality rate was 3.7% (68 patients). CONCLUSIONS As long as the PVTT is limited to the first-order branch, LR is associated with a longer survival outcome than non-surgical treatment. LAY SUMMARY The presence of portal vein tumor thrombosis in patients with hepatocellular carcinoma is regarded as indicating an advanced stage, and liver resection is not recommended. We performed a multicenter, nationwide study to assess the survival benefit of liver resection in hepatocellular carcinoma patients with portal vein tumor thrombosis using propensity score-based matching. As long as the portal vein tumor thrombosis is limited to the first-order branch, liver resection is associated with a longer survival outcome than non-surgical treatment.
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Affiliation(s)
- Takashi Kokudo
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Japan; Division of Gastroenterological Surgery, Saitama Cancer Center, Japan
| | - Kiyoshi Hasegawa
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Japan
| | - Yutaka Matsuyama
- Department of Biostatistics, School of Public Health, The University of Tokyo, Japan
| | - Tadatoshi Takayama
- Department of Digestive Surgery, Nihon University School of Medicine, Japan
| | - Namiki Izumi
- Department of Gastroenterology, Musashino Red Cross Hospital, Japan
| | - Masumi Kadoya
- Department of Radiology, Shinshu University School of Medicine, Japan
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kinki University School of Medicine, Japan
| | - Yonson Ku
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Japan
| | - Michiie Sakamoto
- Department of Pathology, Keio University School of Medicine, Japan
| | - Osamu Nakashima
- Department of Clinical Laboratory Medicine, Kurume University Hospital, Japan
| | - Shuichi Kaneko
- Department of Gastroenterology, Kanazawa University Hospital, Japan
| | - Norihiro Kokudo
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Japan.
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Itoh A, Sadamori H, Yabushita K, Monden K, Tatsukawa M, Hioki M, Hyodo T, Omonishi K, Ueki T, Ohno S, Sakaguchi K, Takakura N. Advanced hepatocellular carcinoma with hepatic vein tumor thrombosis and renal dysfunction after hepatic arterial infusion chemotherapy effectively treated by liver resection with active veno-venous bypass: report of a case. BMC Cancer 2016; 16:705. [PMID: 27586890 PMCID: PMC5009678 DOI: 10.1186/s12885-016-2749-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2015] [Accepted: 08/25/2016] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) patients with hepatic vein tumor thrombosis (HVTT) extending to the inferior vena cava (IVC) have an extremely poor prognosis. Here we report a case of HCC with HVTT and renal dysfunction after hepatic arterial infusion chemotherapy (HAIC) successfully treated by liver resection and active veno-venous bypass. CASE PRESENTATION A 77-year-old man was diagnosed to have a large HCC with intrahepatic metastases and HVTT extending to the IVC. Due to the advanced stage, HAIC with cisplatin was performed 13 times in a period of 17 months. As a consequence of this treatment, the size of the main HCC markedly decreased, and the advanced part of the HVTT went down to the root of the right hepatic vein (RHV). However, because of renal dysfunction, HAIC with cisplatin was discontinued and right hepatectomy with patch graft venoplasty of the root of the RHV was performed. Because progression of renal dysfunction had to be avoided, veno-venous bypass was activated during IVC clamping to prevent renal venous congestion and hypotension. Histological examination showed foci of a moderately differentiated HCC with extensive fibrosis and necrosis in the main HCC. Histologically, the HVTT in the RHV showed massive necrosis and tightly adhered to the vascular wall of the RHV. The postoperative function of the remnant liver was good, and no further deterioration of renal function was detected. The patient did not show signs of recurrence 15 month after surgery. CONCLUSION In the present case, HAIC using cisplatin in combination with hepatic resection and patch graft venoplasty of the IVC provided a good long-term outcome with no HCC recurrence. Renal function was preserved by using active veno-venous bypass during IVC clamping to prevent renal venous congestion and hypotension.
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Affiliation(s)
- Atene Itoh
- Department of Gastroenterological Surgery, Fukuyama City Hospital, 5-23-1 Zao, Fukuyama, 721-8511, Japan
| | - Hiroshi Sadamori
- Department of Gastroenterological Surgery, Fukuyama City Hospital, 5-23-1 Zao, Fukuyama, 721-8511, Japan.
| | - Kazuhisa Yabushita
- Department of Internal Medicine, Fukuyama City Hospital, Fukuyama, Japan
| | - Kazuteru Monden
- Department of Gastroenterological Surgery, Fukuyama City Hospital, 5-23-1 Zao, Fukuyama, 721-8511, Japan
| | - Masashi Tatsukawa
- Department of Internal Medicine, Fukuyama City Hospital, Fukuyama, Japan
| | - Masayoshi Hioki
- Department of Gastroenterological Surgery, Fukuyama City Hospital, 5-23-1 Zao, Fukuyama, 721-8511, Japan
| | - Tsuyoshi Hyodo
- Department of Radiology, Fukuyama City Hospital, Fukuyama, Japan
| | | | - Toru Ueki
- Department of Internal Medicine, Fukuyama City Hospital, Fukuyama, Japan
| | - Satoshi Ohno
- Department of Gastroenterological Surgery, Fukuyama City Hospital, 5-23-1 Zao, Fukuyama, 721-8511, Japan
| | - Kohsaku Sakaguchi
- Department of Internal Medicine, Fukuyama City Hospital, Fukuyama, Japan
| | - Norihisa Takakura
- Department of Gastroenterological Surgery, Fukuyama City Hospital, 5-23-1 Zao, Fukuyama, 721-8511, Japan
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21
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Tumor Regression in HCC Patient with Portal Vein Tumor Thrombosis after Intraportal Radiofrequency Thermal Ablation. Case Reports Hepatol 2016; 2016:6843121. [PMID: 27579192 PMCID: PMC4992757 DOI: 10.1155/2016/6843121] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2016] [Accepted: 07/13/2016] [Indexed: 12/21/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Portal vein tumor thrombosis (PVTT) is a frequent entity in HCC, which strictly limits the gold standard treatment options such as surgical resection and transarterial chemoembolization. Therefore, the prognosis of patients with PVTT is extremely poor and an emergence of seeking an alternative option for intervention is inevitable. We present a case of a 60-year-old male patient with HCC induced PVTT who was subjected to the intraportal RFA and stenting-VesOpen procedure. No additional medical intervention was performed. The repeated CT performed 5 months after the VesOpen procedure revealed significant decrease of the tumor size, patent right, and main portal vein and a recanalization of the left portal vein, which was not processed. At this time point, liver functional tests, appetite, and general condition of the patient were improved evidently. This report designates the RFA as an instrumental option of therapeutic intervention for HCC patients with PVTT.
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22
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Li N, Feng S, Xue J, Wei XB, Shi J, Guo WX, Lau WY, Wu MC, Cheng SQ, Meng Y. Hepatocellular carcinoma with main portal vein tumor thrombus: a comparative study comparing hepatectomy with or without neoadjuvant radiotherapy. HPB (Oxford) 2016; 18:549-56. [PMID: 27317960 PMCID: PMC4913143 DOI: 10.1016/j.hpb.2016.04.003] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2015] [Revised: 03/20/2016] [Accepted: 04/10/2016] [Indexed: 12/12/2022]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) with main portal vein tumor thrombus (mPVTT) has a poor prognosis even after surgical resection. Whether neoadjuvant radiotherapy improves surgical outcomes is currently unknown. The aim of this study was to compare the survival of patients with resectable HCC and mPVTT who underwent neoadjuvant therapy to those who underwent surgery alone. METHODS A non-randomized comparative study was performed. For patients in the neoadjuvant radiotherapy group, three-dimensional conformal radiotherapy was administrated with a daily fraction of 300 cGy in 6 consecutive days. Hepatectomy was carried out 4 weeks after completion of irradiation. RESULTS 95 patients were enrolled into this study. In the neoadjuvant radiotherapy group (n = 45), 12 patients showed gross radiological reduction in extent of PVTT. In 6 patients, the extent of PVTT was reduced to be within the ipsilateral side of the portal vein. When compared with patients who underwent surgery alone (n = 50), neoadjuvant radiotherapy significantly decreased the rates of HCC recurrence and HCC-related death, with hazard ratios of 0.36 (95% CI, 0.19-0.70) and 0.32 (95% CI, 0.18-0.57), respectively. CONCLUSION For patients with HCC with mPVTT, neoadjuvant radiotherapy before partial hepatectomy provided better postoperative survival outcomes than partial hepatectomy alone.
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Affiliation(s)
- Nan Li
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Shuang Feng
- Department of Radiotherapy, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Jie Xue
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Xu-Biao Wei
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Jie Shi
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Wei-Xing Guo
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Wan-Yee Lau
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China,Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China
| | - Meng-Chao Wu
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Shu-Qun Cheng
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China,Correspondence Shu-Qun Cheng, Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai, 200433, China.Department of Hepatic Surgery VIEastern Hepatobiliary Surgery HospitalSecond Military Medical University225 Changhai RoadShanghai200433China
| | - Yan Meng
- Department of Radiotherapy, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China,Correspondence Yan Meng, Department of Radiotherapy, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai, 200433, China.Department of RadiotherapyEastern Hepatobiliary Surgery HospitalSecond Military Medical University225 Changhai RoadShanghai200433China
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Abstract
The nuances of determining resectability for liver tumors can be difficult to navigate, owing to the variety of primary and secondary malignancies involving the liver, the range of patient-specific factors to consider, and the hepatic anatomic and functional variability that seems inevitable. The basic principles, however, are simple;if surgery is deemed appropriate from an oncologic standpoint, the patient is in reasonably good health, and the tumor can be safely removed without compromising the integrity of the future remnant, nearly all patients will be candidates for resection.
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Affiliation(s)
- Cecilia G Ethun
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, 1365C Clifton Road NE, Building C, 2nd Floor, Atlanta, GA 30322, USA
| | - Shishir K Maithel
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, 1365C Clifton Road NE, Building C, 2nd Floor, Atlanta, GA 30322, USA.
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24
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Sun JX, Shi J, Li N, Guo WX, Wu MC, Lau WY, Cheng SQ. Portal vein tumor thrombus is a bottleneck in the treatment of hepatocellular carcinoma. Cancer Biol Med 2016; 13:452-458. [PMID: 28154776 PMCID: PMC5250602 DOI: 10.20892/j.issn.2095-3941.2016.0059] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
The effect of portal vein tumor thrombus (PVTT) on the prognosis of patients with hepatocellular carcinoma has become clear over the past several decades. However, identifying the mechanisms and performing the diagnosis and treatment of PVTT remain challenging. Therefore, this study aimed to summarize the progress in these areas. A computerized literature search in Medline and EMBASE was performed with the following combinations of search terms: “hepatocellular carcinoma” AND “portal vein tumor thrombus.” Although several signal transduction or molecular pathways related to PVTT have been identified, the exact mechanisms of PVTT are still largely unknown. Many biomarkers have been reported to detect microvascular invasion, but none have proved to be clinically useful because of their low accuracy rates. Sorafenib is the only recommended therapeutic strategy in Western countries. However, more treatment options are recommended in Eastern countries, including surgery, radiotherapy (RT), transhepatic arterial chemoembolization (TACE), transarterial radioembolization (TARE), and sorafenib. Therefore, we established a staging system based on the extent of portal vein invasion. Our staging system effectively predicts the long-term survival of PVTT patients. Currently, several clinical trials had shown that surgery is effective and safe in some PVTT patients. RT, TARE, and TACE can also be performed safely in patients with good liver function. However, only a few comparative clinical trials had compared the effectiveness of these treatments. Therefore, more randomized controlled trials examining the extent of PVTT should be conducted in the future.
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Affiliation(s)
- Ju-Xian Sun
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgical Hospital, Shanghai 200438, China
| | - Jie Shi
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgical Hospital, Shanghai 200438, China
| | - Nan Li
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgical Hospital, Shanghai 200438, China
| | - Wei-Xing Guo
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgical Hospital, Shanghai 200438, China
| | - Meng-Chao Wu
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgical Hospital, Shanghai 200438, China
| | - Wan-Yee Lau
- Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, SAR 999077, China
| | - Shu-Qun Cheng
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgical Hospital, Shanghai 200438, China
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25
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Zhang YF, Guo RP, Zou RH, Shen JX, Wei W, Li SH, OuYang HY, Zhu HB, Xu L, Lao XM, Shi M. Efficacy and safety of preoperative chemoembolization for resectable hepatocellular carcinoma with portal vein invasion: a prospective comparative study. Eur Radiol 2015; 26:2078-88. [PMID: 26396105 DOI: 10.1007/s00330-015-4021-8] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2014] [Revised: 09/01/2015] [Accepted: 09/09/2015] [Indexed: 12/14/2022]
Abstract
OBJECTIVES To evaluate the outcomes of preoperative transarterial chemoembolization (TACE) for resectable hepatocellular carcinoma (HCC) with portal vein invasion. METHODS From February 2006 to July 2011, 320 patients initially diagnosed with resectable HCC and portal vein invasion were prospectively non-randomized into two arms. In the immediate resection arm (Arm 1, n = 205) patients received immediate surgical resection. 115 patients were included in the preoperative TACE arm (Arm 2), and eventually 85 patients underwent TACE followed by surgical resection. RESULTS The 1-, 3- and 5-year overall survival rates were 48.3 %, 18.7 % and 13.9 % for Arm 1 and 61.2 %, 31.7 % and 25.3 % for Arm 2 (P = 0.001), respectively. In the subgroup analysis of types I and II portal vein tumour thrombus (PVTT), the preoperative TACE arm demonstrated significantly better survival rates than the immediate resection arm (P I = 0.001, P II = 0.036). However, no significant difference was found for patients with type III PVTT (P III = 0.684). No significant difference was found between the two arms in terms of complications and mortality. CONCLUSIONS Preoperative TACE seems to confer a survival benefit for resectable HCC with PVTT, especially for types I and II PVTT, and preoperative TACE should therefore be recommended as a routine procedure. KEY POINTS • Preoperative TACE improves the clinical outcomes for patients with PVTT • Preoperative TACE could significantly improve the rate of en bloc thrombectomy • Preoperative TACE does not increase the related adverse events.
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Affiliation(s)
- Yong-Fa Zhang
- State Key Laboratory of Oncology in South China, Guangzhou, China.,Department of Hepatobiliary Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, 510060, People's Republic of China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China
| | - Rong-Ping Guo
- State Key Laboratory of Oncology in South China, Guangzhou, China.,Department of Hepatobiliary Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, 510060, People's Republic of China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China
| | - Ru-Hai Zou
- State Key Laboratory of Oncology in South China, Guangzhou, China.,Department of Ultrasound, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China
| | - Jing-Xian Shen
- State Key Laboratory of Oncology in South China, Guangzhou, China.,Department of Radiology, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China
| | - Wei Wei
- State Key Laboratory of Oncology in South China, Guangzhou, China.,Department of Hepatobiliary Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, 510060, People's Republic of China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China
| | - Shao-Hua Li
- State Key Laboratory of Oncology in South China, Guangzhou, China.,Department of Hepatobiliary Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, 510060, People's Republic of China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China
| | - Han-Yue OuYang
- State Key Laboratory of Oncology in South China, Guangzhou, China.,Department of Hepatobiliary Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, 510060, People's Republic of China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China
| | - Hong-Bo Zhu
- Department of Medical Oncology of the First Affiliated Hospital of the University of South China, Hengyang, China
| | - Li Xu
- State Key Laboratory of Oncology in South China, Guangzhou, China.,Department of Hepatobiliary Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, 510060, People's Republic of China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China
| | - Xiang-Ming Lao
- State Key Laboratory of Oncology in South China, Guangzhou, China.,Department of Hepatobiliary Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, 510060, People's Republic of China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China
| | - Ming Shi
- State Key Laboratory of Oncology in South China, Guangzhou, China. .,Department of Hepatobiliary Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, 510060, People's Republic of China. .,Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.
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Ogasawara S, Chiba T, Ooka Y, Kanogawa N, Motoyama T, Suzuki E, Tawada A, Azemoto R, Shinozaki M, Yoshikawa M, Yokosuka O. A prognostic score for patients with intermediate-stage hepatocellular carcinoma treated with transarterial chemoembolization. PLoS One 2015; 10:e0125244. [PMID: 25919025 PMCID: PMC4412579 DOI: 10.1371/journal.pone.0125244] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2014] [Accepted: 03/22/2015] [Indexed: 02/06/2023] Open
Abstract
Background Intermediate-stage hepatocellular carcinoma (HCC), defined according to the Barcelona Clinic Liver Cancer (BCLC) staging system, is a heterogeneous condition with variable clinical benefits from transarterial chemoembolization (TACE). This study aimed to develop a simple validated prognostic score based on the predictive factors for survival in patients with intermediate-stage HCC treated with TACE. Methods Three-hundred and fifty patients with intermediate-stage HCC undergoing initial TACE at Chiba University Hospital (training cohort; n = 187) and two affiliated hospitals (validation cohort; n = 163) were included. Following variables were entered into univariate and multivariate Cox regression models to develop a points-based clinical scoring system: gender, age, etiology, pretreatment, Child–Pugh score, aspartate aminotransferase, creatinine, C-reactive protein, alfa-fetoprotein, size of the largest lesion, and number and location of lesions. Results The number of lesions and the Child–Pugh score were identified as independent prognostic factors in the training cohort. The development of a 0–7-point prognostic score, named the Chiba HCC in intermediate-stage prognostic (CHIP) score, was based on the sum of three subscale scores (Child–Pugh score = 0, 1, 2, or 3, respectively, number of lesions = 0, 2, or 3, respectively, HCV-RNA positivity = 0 or 1, respectively). The generated scores were then differentiated into five groups (0–2 points, 3 points, 4 points, 5 points, and 6–7 points) by the median survival time (65.2, 29.2, 24.3, 13.1, and 8.4 months, respectively; p < 0.0001). These results were confirmed in the external validation cohort (p < 0.0001). Conclusions The CHIP score is easy-to-use and may assist in finding an appropriate treatment strategy for intermediate-stage HCC.
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Affiliation(s)
- Sadahisa Ogasawara
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Tetsuhiro Chiba
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
- * E-mail:
| | - Yoshihiko Ooka
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Naoya Kanogawa
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Tenyu Motoyama
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Eiichiro Suzuki
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Akinobu Tawada
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Ryosaku Azemoto
- Department of Gastroenterology, Kimitsu Chuo Hospital, Chiba, Japan
| | - Masami Shinozaki
- Department of Gastroenterology, Numazu City Hospital, Shizuoka, Japan
| | - Masaharu Yoshikawa
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Osamu Yokosuka
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
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27
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Zhong JH, Rodríguez AC, Ke Y, Wang YY, Wang L, Li LQ. Hepatic resection as a safe and effective treatment for hepatocellular carcinoma involving a single large tumor, multiple tumors, or macrovascular invasion. Medicine (Baltimore) 2015; 94:e396. [PMID: 25621684 PMCID: PMC4602643 DOI: 10.1097/md.0000000000000396] [Citation(s) in RCA: 107] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2014] [Revised: 11/25/2014] [Accepted: 11/26/2014] [Indexed: 01/27/2023] Open
Abstract
This systematic review examined whether the available evidence justifies using hepatic resection (HR) during later stages of hepatocellular carcinoma (HCC), which contravenes treatment guidelines but is current practice at many medical centers.Official guidelines and retrospective studies recommend different roles for HR for patients with large/multinodular HCC or with HCC involving macrovascular invasion (MVI).Several databases were systematically searched for studies examining the safety and efficacy of HR for treating HCC involving a single large tumor (>5 cm) or multiple tumors, or for treating HCC involving MVI.We identified 50 studies involving 14, 808 patients that investigated the use of HR to treat large/multinodular HCC, and 24 studies with 4389 patients that investigated HR to treat HCC with MVI. Median in-hospital mortality for patients with either type of HCC was significantly lower in Asian studies (2.7%) than in non-Asian studies (7.3%, P < 0.001). Median overall survival (OS) was significantly higher for all Asian patients with large/multinodular HCC than for all non-Asian patients at both 1 year (81% vs 65%, P < 0.001) and 5 years (42% vs 32%, P < 0.001). Similar results were obtained for median disease-free survival at 1 year (61% vs 50%, P < 0.001) and 5 years (26% vs 24%, P < 0.001). However, median OS was similar for Asian and non-Asian patients with HCC involving MVI at 1 year (50% vs 52%, P = 0.45) and 5 years (18% vs 14%, P = 0.94). There was an upward trend in 5-year OS in patients with either type of HCC.HR is reasonably safe and effective at treating large/multinodular HCC and HCC with MVI. The available evidence argues for expanding the indications for HR in official treatment guidelines.
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Affiliation(s)
- Jian-Hong Zhong
- From the Department of Hepatobiliary Surgery (J-HZ, ACR, Y-YW, L-QL), Affiliated Tumor Hospital of Guangxi Medical University, Nanning; Department of Research (ACR), Creaducate Enterprises Ltd, Kowloon, Hong Kong; and Department of Hepatobiliary Surgery (YK, LW), The Second Affiliated Hospital of Kunming Medical University, Kunming, PR China
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Morise Z, Kawabe N, Tomishige H, Nagata H, Kawase J, Arakawa S, Yoshida R, Isetani M. Recent advances in the surgical treatment of hepatocellular carcinoma. World J Gastroenterol 2014; 20:14381-14392. [PMID: 25339825 PMCID: PMC4202367 DOI: 10.3748/wjg.v20.i39.14381] [Citation(s) in RCA: 67] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2014] [Revised: 05/25/2014] [Accepted: 07/16/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. The treatment of HCC is complex and complicated by the severity of associated chronic liver disease, the stage of HCC, and the clinical condition of the patient. Liver resection (LR) is one of the most efficient treatments for patients with HCC, with an expected 5-year survival of 38%-61% depending on the stage of the disease. Improved liver function assessment, increased understanding of segmental liver anatomy from advanced imaging studies, and surgical technical progress are important factors that have led to reduced mortality in patients with HCC. The indication for LR may be expanded due to emerging evidences from laparoscopic hepatectomies and combined treatments with newly developed chemotherapies. Liver transplantation (LT) is considered as an ideal treatment for removal of existing tumors and the injured/preneoplastic underlying liver tissue with impaired liver function and the risk of multicentric carcinogenesis that results from chronically injured liver. However, LT is restricted to patients with minimal risk of tumor recurrence under immunosuppression. The expansion of criteria for LT in HCC patients is still under trial and discussion. Limited availability of grafts, as well as the risk and the cost of transplantation have led to considerable interest in expansion of the donor pool, living donor-related transplantation, and combined treatment involving LR and LT. This highlight presents evidence concerning recent studies evaluating LR and LT in HCC patients. In addition, alternative therapies for the treatment of early stage tumors and the management of patients on transplant waiting lists are discussed.
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Tan X, Xie P, Liu J, Wu H, Xie Y. Therapeutic value of transcatheter arterial chemoembolization combined with portal vein embolization for primary hepatocellular carcinoma with portal vein tumor thrombus: a pilot study. Asia Pac J Clin Oncol 2014; 11:e6-e12. [PMID: 25228074 DOI: 10.1111/ajco.12272] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/20/2014] [Indexed: 01/11/2023]
Abstract
AIM To compare clinical outcome and safety of transcatheter arterial chemoembolization (TACE) + portal vein embolization (PVE) with TACE alone in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT). METHODS We retrospectively collected patients of HCC with PVTT treated with TACE (5-FU, oxaliplatin and mitomycin) or TACE + PVE (doxorubicin) between October 2000 and July 2008. Outcomes evaluated include overall survival, response to treatment and side effects. RESULTS One hundred and sixteen patients were assessed. The median follow-up of TACE group and TACE + PVE group was 83 and 85 months, respectively. The tumor response rates were respectively 48/64 and 49/52. The 1-, 3- and 5-year overall survival rates for the TACE and TACE + PVE groups were 39/64, 16/64, 0/64 and 42/52, 19/52, 6/52 respectively (P = 0.015, 0.046 and 0.002, respectively). Three factors were shown as the risk factors which affect the survival of patients: treated by TACE + PVE or TACE; type of PVTT; and absence of cirrhosis. CONCLUSION TACE + PVE may be better than TACE alone to treat primary HCC with PVTT.
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Affiliation(s)
- Xuefen Tan
- Department of Chemotherapy Oncology, Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Jinan, Shandong Province, China
| | - Peng Xie
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Jinan, Shandong Province, China
| | - Jibing Liu
- Department of Interventional Radiology, Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Jinan, Shandong Province, China
| | - Huiyong Wu
- Department of Interventional Radiology, Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Jinan, Shandong Province, China
| | - Yinfa Xie
- Department of Interventional Radiology, Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Jinan, Shandong Province, China
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Morise Z, Kawabe N, Tomishige H, Nagata H, Kawase J, Arakawa S, Yoshida R, Isetani M. Recent advances in liver resection for hepatocellular carcinoma. Front Surg 2014; 1:21. [PMID: 25593945 PMCID: PMC4286985 DOI: 10.3389/fsurg.2014.00021] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2014] [Accepted: 06/03/2014] [Indexed: 12/11/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. The association of HCC with chronic liver disease (CLD) is well known and making treatment complex and challenging. The treatment of HCC must take into consideration, the severity of CLD, the stage of HCC, and the clinical condition of the patient. Liver resection (LR) is one of the most efficient treatments for patients with HCC. Better liver function assessment, increased understanding of segmental liver anatomy using more accurate imaging studies, and surgical technical progress are the important factors that have led to reduced mortality, with an expected 5 year survival of 38-61% depending on the stage of the disease. However, the procedure is applicable to <30% of all HCC patients, and 80% of the patients after LR recurred within 5 years. There are recent advances and prospects in LR for HCC in several aspects. Three-dimensional computed tomography imaging assisted preoperative surgical planning facilitates unconventional types of LR. Emerging evidences of laparoscopic hepatectomy and prospects for the use of newly developing chemotherapies as a combined therapy may lead to expanding indication of LR. LR and liver transplantation could be associated rather than considered separately with the current concepts of "bridging LR" and "salvage transplantation."
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Affiliation(s)
- Zenichi Morise
- Department of Surgery, Banbuntane Houtokukai Hospital, Fujita Health University School of Medicine, Nagoya, Japan
| | - Norihiko Kawabe
- Department of Surgery, Banbuntane Houtokukai Hospital, Fujita Health University School of Medicine, Nagoya, Japan
| | - Hirokazu Tomishige
- Department of Surgery, Banbuntane Houtokukai Hospital, Fujita Health University School of Medicine, Nagoya, Japan
| | - Hidetoshi Nagata
- Department of Surgery, Banbuntane Houtokukai Hospital, Fujita Health University School of Medicine, Nagoya, Japan
| | - Jin Kawase
- Department of Surgery, Banbuntane Houtokukai Hospital, Fujita Health University School of Medicine, Nagoya, Japan
| | - Satoshi Arakawa
- Department of Surgery, Banbuntane Houtokukai Hospital, Fujita Health University School of Medicine, Nagoya, Japan
| | - Rie Yoshida
- Department of Surgery, Banbuntane Houtokukai Hospital, Fujita Health University School of Medicine, Nagoya, Japan
| | - Masashi Isetani
- Department of Surgery, Banbuntane Houtokukai Hospital, Fujita Health University School of Medicine, Nagoya, Japan
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Yip VS, Gomez D, Tan CY, Staettner S, Terlizzo M, Fenwick S, Malik HZ, Ghaneh P, Poston G. Tumour size and differentiation predict survival after liver resection for hepatocellular carcinoma arising from non-cirrhotic and non-fibrotic liver: a case-controlled study. Int J Surg 2013; 11:1078-82. [PMID: 24129124 DOI: 10.1016/j.ijsu.2013.10.001] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2013] [Revised: 09/22/2013] [Accepted: 10/02/2013] [Indexed: 02/07/2023]
Abstract
AIMS The aims of this study were to assess the outcomes of patients who underwent potentially curative hepatic resection for hepatocellular carcinoma (HCC) in a background of non-cirrhotic/non-fibrotic livers, and to determine prognostic factors that influenced survival. METHODS Over a 15-year period, all patients undergoing hepatectomy for HCC were identified. Collated data included demographics, laboratory analysis, operative findings and histo-pathological data. Survival differences between these factors following liver resection were determined. RESULTS 57 patients were included with a median age of 70 years. The majority of patients underwent a hemi-hepatectomy or more radical resection (n = 37). Overall R0 resection rate was 90.4% (n = 51). The overall morbidity and mortality rates were 26.3% and 3.5%, respectively. The median follow-up period was 28 months. The 1-, 3- and 5- year disease-free survival was 65.4%, 41.8% and 39.1%, and the overall survival was 73.5%, 49.6% and 39.5%, respectively. AFP (p = 0.039) was the only predictor of poorer disease-free survival on univariate analysis. On multi-variable analysis, poorly differentiated tumour and large tumour size were independent predictors of overall survival. CONCLUSIONS Liver resection is a feasible treatment option for HCC in non-cirrhotic/non-fibrotic livers with good survival outcome. Tumour size and differentiation are adverse predictors of outcome in these patients.
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Affiliation(s)
- V S Yip
- North Western Hepatobiliary Unit, Aintree University Hospital NHS Foundation Trust, Liverpool, UK.
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Huang J, Zhang Y, Peng Z, Gao H, Xu L, Jiao LR, Chen M. A modified TNM-7 staging system to better predict the survival in patients with hepatocellular carcinoma after hepatectomy. J Cancer Res Clin Oncol 2013; 139:1709-19. [PMID: 23982274 DOI: 10.1007/s00432-013-1497-y] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2013] [Accepted: 08/15/2013] [Indexed: 02/08/2023]
Abstract
OBJECTIVE To evaluate the accuracy of the 7th edition of the American Joint Committee on Cancer staging system (TNM-7) for patients undergoing hepatectomy for hepatocellular carcinoma (HCC) and to propose a modified TNM system for better prediction of survival. METHODS Clinico-pathological data for 1,313 patients who underwent hepatectomy as initial treatment for HCC between 2000 and 2008 were retrieved from a prospective database. Overall survival (OS) and disease-free survival (DFS) were analyzed to evaluate the predictive value. RESULTS The 1-, 3-, 5-year OS and DFS of 1,313 patients were 79.2, 55.4, 45.5 %, and 52.6, 36.1, 31.8 %, respectively. Multivariate analysis revealed that major vascular invasion was the most important prognostic factor for both OS and DFS, along with tumour number and size. Patients with pT1 and pT2 disease had significantly better OS and DFS than those with pT3 disease (P < 0.001). There was no significant difference between pT3a and pT4 (P = 0.552) but patients with pT3b disease had a worse OS and DFS than those with pT4 disease (P = 0.006 and P < 0.001, respectively). A modified TNM system within the existing framework was proposed to combine the current pT3a and pT4 together as the new pT3 and to change pT3b to the new pT4. Analysis showed that this modified system had a better prognostic power than either TNM-6 or TNM-7. CONCLUSION TNM-7 would seem to be inaccurate for staging advanced HCC. The modified system can improve both the prognostic accuracy and the hazard discrimination of disease to be consistent among subgroups of HCC.
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Affiliation(s)
- Junting Huang
- Department of Hepatobiliary Surgery, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, China
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Kee KM, Wang JH, Lin CY, Wang CC, Cheng YF, Lu SN. Validation of the 7th edition TNM staging system for hepatocellular carcinoma: an analysis of 8,828 patients in a single medical center. Dig Dis Sci 2013; 58:2721-8. [PMID: 23703450 DOI: 10.1007/s10620-013-2716-8] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2012] [Accepted: 05/08/2013] [Indexed: 12/15/2022]
Abstract
BACKGROUND Major modification of the 7th tumor-node-metastasis (TNM) staging system for hepatocellular carcinoma (HCC) was divided into 6th stage IIIA to 7th IIIA (multiple tumors, any>5 cm) and IIIB (tumors involving a major vessel). This study aimed to validate 6th and 7th TNM systems in prognostic prediction, then analyze the impact of time, Child-Pugh classification and treatment modalities in survival. METHODS A total of 5,611 and 3,217 HCC patients were enrolled between 1986-2002 (past period) and 2003-2010 (recent period), respectively. The Akaike information criteria (AIC) within a Cox proportional hazard regression model were used to demonstrate the discriminatory ability for staging systems. RESULTS The 1-, 3-, and 5-year survival rates of past and recent periods were 44.8, 24.9, 17.1%, and 65.5, 44.5, 34.6%, respectively (p<0.001). Rates of smaller HCC detection and received curative treatment were significantly higher in the recent period than in the past period (p<0.001). Survival rates were different in each Child-Pugh class (all p<0.001). Patients receiving curative treatment had highest survival rates, followed by non-curative treatment, and untreated patients (p<0.05). In both periods, significant differences in survival curves existed between each of the stages in the 6th and 7th TNM staging (all p<0.05), and also between IIIA and IIIB in the 7th TNM (p<0.001). The AIC of two periods in the 6th and 7th TNM systems were decreased, with 77,895 and 77,630, and 19,162 and 19,135, respectively. CONCLUSION The 7th TNM provided better prognostic prediction than the 6th TNM after dividing into IIIA and IIIB. Survival rates of HCC have been improving in recent decades.
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Affiliation(s)
- Kwong-Ming Kee
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Ta Pei Road, Niao Sung District, Kaohsiung, 833, Taiwan
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Abstract
Hepatocellular carcinoma is one of the most common malignancies worldwide, and its incidence continues to rise in the United States. Partial hepatectomy and liver transplantation remains the mainstay of treatment for localized disease and provides significant improvement in long-term survival, as well as the potential for cure. The indications and criteria for resection and transplantation are well established, but continue to undergo significant modification over time. Surgical resection is the primary therapeutic modality in patients with well-compensated liver disease, and transplantation is highly effective in early-stage tumors in patients with severe underlying liver disease. The relative role for each of these modalities must be tailored to individual patients based on a rational approach designed to balance quality of life, organ allocation, and patient survival.
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Lou L, Chen YX, Jin L, Li X, Tao X, Zhu J, Chen X, Wu S, Ye W, He J, Ding G. Enhancement of invasion of hepatocellular carcinoma cells through lysophosphatidic acid receptor. J Int Med Res 2013; 41:55-63. [PMID: 23569130 DOI: 10.1177/0300060512474124] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
OBJECTIVES Lysophosphatidic acid (LPA) is a bioactive lipid mediator involved in tumour progression, cell invasion and metastasis. The mechanism of action of LPA in the invasive and metastatic capacity of human hepatocellular carcinoma (HCC) is not fully understood. This study investigated the effects of LPA on HCC cell invasion and induction of matrix metalloproteinase (MMP) -2 and -9. METHODS LPA receptor levels in HCC cell lines were detected by Western blot analysis; HCC cell invasion was analysed by the Transwell® system. The LPA receptor blocker Ki16425 was used to determine whether HCC cell invasion was LPA dependent. Expression of the MMP2 and MMP9 genes in HCC cells was determined by real-time quantitative reverse transcription-polymerase chain reaction (qPCR). RESULTS LPA increased HCC cell invasion, which was LPA-receptor dependent. Real-time RT-qPCR showed that LPA increased MMP9, but not MMP2, expression in HCC cells. Pharmacological inhibition of LPA receptors with Ki16452 significantly attenuated LPA-induced HCC cell invasion. CONCLUSIONS HCC invasiveness is facilitated by LPA and may be relevant to tumour progression. Thus, LPA receptors may be a potential therapeutic target for HCC.
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Affiliation(s)
- Lianqing Lou
- Department of Infectious Diseases, The Affiliated Yiwu Hospital of Wenzhou Medical College, Zhejiang Yiwu, China
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NAGANO HIROAKI, KOBAYASHI SHOGO, MARUBASHI SHIGERU, WADA HIROSHI, EGUCHI HIDETOSHI, TANEMURA MASAHIRO, TOMIMARU YOSHITO, UMESHITA KOJI, DOKI YUICHIRO, MORI MASAKI. Combined IFN-α and 5-FU treatment as a postoperative adjuvant following surgery for hepatocellular carcinoma with portal venous tumor thrombus. Exp Ther Med 2013; 5:3-10. [PMID: 23251233 PMCID: PMC3524132 DOI: 10.3892/etm.2012.736] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2011] [Accepted: 11/30/2011] [Indexed: 12/13/2022] Open
Abstract
The efficacy of combination therapy with subcutaneous interferon (IFN)-α and intra-arterial 5-fluorouracil (5-FU) as a postoperative adjuvant for resectable advanced hepatocellular carcinoma (HCC) invading the major branches of the portal vein (PVTT) was examined. The prognosis of HCC with PVTT (Vp3 or 4) is extremely poor. Recently, we reported the possibility of combination therapy with IFN-α and intra-arterial 5-FU for intractable HCC with PVTT as a postoperative adjuvant and this is the second report. Patients with HCC with PVTT were included (n=50). Thirty consecutive patients with HCC and PVTT were treated with 3 cycles of a combination therapy consisting of arterial 5-FU infusion (300 mg/mm(3)/day, 5 days/week, for the initial 2 weeks) and IFN subcutaneous injection (5 MIU, 3 times/week, 4 weeks) as a postoperative adjuvant following hepatic resection; another 20 patients receiving no IFN/5-FU chemotherapy acted as controls. Results for the IFN/5-FU adjuvant treatment group were as follows: disease-free survival (n=9, 15-109 months), survival with recurrence (n=6, 30-92 months), cancer death (n=9, 14-60 months), death from other causes but no recurrence (n=5, 13-87 months) and death from other causes with recurrence (n=1, 22 months). The 1-year survival rate was 100% in patients treated with IFN/5-FU, and 30% in those without IFN/5-FU as historical controls (n=20). There was a significant difference in disease-free and overall survival rates between the two groups (P<0.0001). In conclusion, IFN/5-FU combination therapy may be a very promising postoperative adjuvant treatment for HCC with PVTT.
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Affiliation(s)
| | | | | | | | | | | | | | - KOJI UMESHITA
- Health Science, Graduate School of Medicine, Osaka University, Osaka,
Japan
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A case of hepatocellular carcinoma with portal vein tumor thrombosis successfully treated by a combination of intra-arterial infusion 5-fluorouracil, cisplatin, and systemic interferon-α therapies. Int Surg 2012; 97:230-4. [PMID: 23113851 DOI: 10.9738/cc24.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
A 58-year-old female with hepatitis C was referred to our hospital after computed tomography (CT) revealed a tumor in the right lobe of her liver. After thorough examination, tumor thrombosis was detected on the main trunk of the portal vein, and we decided to administer a combination of subcutaneous interferon-alfa and intra-arterial 5-fluorouracil. However, after 2 cycles of treatment, this regimen was ineffective, and thus cisplatin (CDDP) was added for the third cycle. On completion of 5 treatment cycles, the tumor and portal vein tumor thrombosis were not detected by CT or (18)F-2-fluoro-2-deoxy-D-glucose positron emission tomography. Hence, chemotherapy was considered effective and stopped. Two years after chemotherapy, Alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonists-II (PIVKA-II) levels were within normal limits. Combination therapies have been recognized recently, and judging from the above case, the addition of CDDP to the combination regimen can prove beneficial.
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Zhou YM, Sui CJ, Li B, Xu F, Kan T, Yang JM. Results of en bloc resection for hepatocellular carcinoma extending to adjacent organs. Can J Surg 2012; 55:222-6. [PMID: 22617536 DOI: 10.1503/cjs.028410] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND To curatively resect hepatocellular carcinoma (HCC) with adjacent organ extension, the combined resection of these organs is inevitable. We analyzed the safety and effectiveness of en bloc resection for HCC extending to adjacent organs. METHODS From December 2002 to May 2006, we compared the surgical outcomes of patients with HCC extending to adjacent organs with those of closely matched, randomly selected patients with HCC without adjacent organ extension. RESULTS We included 42 patients whose HCC extended to adjacent organs and 126 patients whose HCC did not extend to adjacent organs. There was no significant difference in survival, operative morbidity or mortality between the groups. In patients with HCC extending to adjacent organs, histopathological examination of the specimen revealed true tumour invasion in 13 and adhesion in 29 patients. Those with tumour invasion were more likely to have a high incidence of capsule infiltration, microvascular invasion and early intrahepatic recurrence (≤ 1 yr after hepatectomy). The 5-year overall survival of patients with tumour invasion was 11.5%, whereas that of patients with tumour adhesion was 38.1% (p = 0.033). CONCLUSION En bloc resection is a safe and effective therapy for HCC extending to adjacent organs. Tumour invasion to adjacent organs exhibits a more aggressive clinical behaviour and is associated with worse survival than tumour adhesion.
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Affiliation(s)
- Yan-Ming Zhou
- Department of Hepato-Biliary-Pancreato-Vascular Surgery, First Affiliated Hospital of Xiamen University, Xiamen, China
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Chan SC, Fan ST, Chok KSH, Cheung TT, Chan ACY, Fung JYY, Poon RTP, Lo CM. Survival advantage of primary liver transplantation for hepatocellular carcinoma within the up-to-7 criteria with microvascular invasion. Hepatol Int 2012; 6:646-656. [PMID: 22016140 PMCID: PMC3360855 DOI: 10.1007/s12072-011-9318-3] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2011] [Accepted: 10/01/2011] [Indexed: 02/06/2023]
Abstract
PURPOSE Microvascular invasion of hepatocellular carcinoma (HCC) is considered a poor prognostic factor of liver resection (LR) and liver transplantation (LT), but its significance for lesions within the up-to-7 criteria is unclear. This study investigated the survival benefit of primary LT against LR for HCC with microvascular invasion and within the up-to-7 criteria. METHODS Adult patients who underwent LR or LT as the primary treatment for HCC were included for study. Patients with prior local ablation, neoadjuvant systemic chemotherapy, targeted therapy, positive resection margin, or metastatic spread were excluded. RESULTS There were 471 LR patients and 95 LT recipients (70 with living donor, 25 with deceased donor). Seventy-seven (81.1%) LT recipients had HCC within the up-to-7 criteria. Twenty-five (26.3%) LT recipients had HCC with either macrovascular (n = 4) or microvascular (n = 21) invasion. The 5-year survival rate was 85.7% for LT recipients with HCC within the up-to-7 criteria, unaffected by the presence or absence of vascular invasion (88.2 vs. 85.1%). The rate was comparable with that of LR patients with HCC without vascular invasion (81.2%, p 0.227), but far superior to that of LR patients with lesions with vascular invasion (50.0%, p < 0.0001). Overall survivals were compromised by multiple tumors [odds ratio (OR) 1.902, confidence interval (CI) 1.374-2.633, p = 0.0001], vascular invasion (OR 2.678, CI 1.952-3.674, p < 0.0001), blood transfusion (OR 2.046, CI 1.337-3.131, p = 0.001), and being beyond the up-to-7 criteria (OR 1.457, CI 1.041-2.037, p = 0.028). LT was a favorable factor for survival (OR 0.243, CI 0.130-0.454, p < 0.0001). CONCLUSION Primary LT for HCC with microvascular invasion and within the up-to-7 criteria doubled the chance of cure as compared with LR.
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Affiliation(s)
- See Ching Chan
- State Key Laboratory for Liver Research, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, China
- Department of Surgery, The University of Hong Kong, Hong Kong, China
| | - Sheung Tat Fan
- State Key Laboratory for Liver Research, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, China
- Department of Surgery, The University of Hong Kong, Hong Kong, China
| | | | - Tan To Cheung
- Department of Surgery, The University of Hong Kong, Hong Kong, China
| | - Albert C. Y. Chan
- Department of Surgery, The University of Hong Kong, Hong Kong, China
| | - James Y. Y. Fung
- Department of Medicine, The University of Hong Kong, Hong Kong, China
| | - Ronnie T. P. Poon
- State Key Laboratory for Liver Research, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, China
- Department of Surgery, The University of Hong Kong, Hong Kong, China
| | - Chung Mau Lo
- State Key Laboratory for Liver Research, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, China
- Department of Surgery, The University of Hong Kong, Hong Kong, China
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Song MK, Kim YJ, Song M, Choi HS, Park YK, Ryu JC. Polycyclic aromatic hydrocarbons induce migration in human hepatocellular carcinoma cells (HepG2) through reactive oxygen species-mediated p38 MAPK signal transduction. Cancer Sci 2011; 102:1636-44. [PMID: 21635667 PMCID: PMC11158662 DOI: 10.1111/j.1349-7006.2011.02000.x] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023] Open
Abstract
Although polycyclic aromatic hydrocarbons (PAHs) are carcinogenic and have been extensively studied with regard to tumor formation, few studies have investigated the involvement of these environmental chemicals in tumor migration and invasion. Polycyclic aromatic hydrocarbons induce reactive oxygen species (ROS) and activate MAPK signal transduction. The p38 signaling transduction pathway, one of the most typical MAPK pathways, plays an essential role in regulating cell migration. Therefore, we investigated whether three PAHs, benzo[a]anthracene (B[a]A), benzo[k]fluoranthene (B[k]F), and indeno[1,2,3-c,d]pyrene (IND), induce migration in human hepatocellular carcinoma cell line HepG2 through ROS-mediated p38 MAPK signal transduction. Reactive oxygen species generation and p38 MAPK activity both increased in a dose-dependent manner and were prevented by SB203580, an inhibitor of p38 MAPK, and N-acetylcysteine (NAC), a ROS scavenger. Expression of migration-related genes was also increased by B[a]A, B[k]F, and IND in a dose-dependent manner and was inhibited by SB203580 and NAC. The migration of HepG2 cells, observed using the Transwell migration assay, also increased in a dose-dependent manner and was prevented by SB203580 and NAC. Our results indicate that the ROS-mediated p38 MAPK signaling pathway plays an essential role in the PAH-induced migration of HepG2 cells.
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Affiliation(s)
- Mi-Kyung Song
- Cellular and Molecular Toxicology Laboratory, Korea Institute of Science and Technology, Seoul, Korea
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Treatment strategy for hepatocellular carcinoma with major portal vein or inferior vena cava invasion: a single institution experience. J Am Coll Surg 2011; 212:796-803. [PMID: 21530845 DOI: 10.1016/j.jamcollsurg.2011.01.002] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2010] [Revised: 12/27/2010] [Accepted: 01/03/2011] [Indexed: 02/07/2023]
Abstract
BACKGROUND The prognosis of patients with hepatocellular carcinoma (HCC) invading the main trunk of the portal vein and the inferior vena cava is dismal. The best strategy for treatment is not well known. STUDY DESIGN We retrospectively reviewed the medical records of 641 patients treated for HCC between 1990 and June 2009. Eighty-four (13%) of these patients had HCC, with a tumor thrombus invading the main trunk or the first-order branch of the portal vein, or the inferior vena cava. Thirty-four patients underwent hepatectomy and 50 patients underwent transcatheter arterial chemoembolization (TACE). We specifically focused on these 34 patients to describe our results of surgical treatment for advanced HCC. RESULTS Among the 34 patients who underwent hepatectomy, preoperative TACE was performed in 15 patients. Six patients were identified as having a tumor size reduction or necrosis of 50% or higher (TE3) by TACE. The median operative duration was 355 minutes. Postoperative morbidity and mortality rates were 44% and 2.9%, respectively. The 5-year survival rate after hepatectomy was 20%, which was better than that of patients after TACE alone. The response after preoperative TACE (hazard ratio 4.65; 95% CI, 1.39 to 15.5) and tumor diameter (hazard ratio 2.78; 95% CI, 1.16 to 6.64) were identified as significant favorable preoperative prognostic factors for survival using the multivariable Cox model. Patients with tumors smaller than 10 cm and TE3 effect had a more favorable survival than patients with tumors 10 cm or larger and who did not have a good TACE outcome. CONCLUSIONS A combination of aggressive surgical treatment and effective preoperative TACE treatment for HCC with major vascular invasion may be beneficial for selected patients.
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Alvite Canosa M, Pita Fernández S, Quintela Fandiño J, Aguirrezabalaga J, Otero A, Suárez F, Corbal G, Fernández C, Gutiérrez MG. [Surgical treatment of liver cancer: experience of the A Coruña UHC (Spain)]. Cir Esp 2011; 89:223-9. [PMID: 21353668 DOI: 10.1016/j.ciresp.2010.12.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2010] [Revised: 10/21/2010] [Accepted: 12/02/2010] [Indexed: 12/18/2022]
Abstract
INTRODUCTION Liver cancer (LC) is one of the most frequent tumours, in which the potentially curative treatment is surgery: partial surgical resection or liver transplant. OBJECTIVES To determine the morbidity and mortality, survival, and their associated factors in patients with LC, according to the type of surgical treatment: partial surgical resection or liver transplant. MATERIAL AND METHODS A retrospective, observational follow-up study of LC patients diagnosed and treated from June 1994 to December 2007. A descriptive analysis of the variables was performed, as well as a Kaplan- Meier survival analysis and Cox regression. RESULTS The incidence of tumour recurrence in the 150 transplant patients was 13.3%, with a survival at 1, 3, and 5 years of 89.3%, 73.1% and 61.4%, respectively. The multivariate analysis showed that only the histological grade/differentiation was an independent risk factor. In the 33 patients with partial surgical resection, the incidence of tumour was 51.5%, with a survival at 1, 3, and 5 years of 90.9%, 60.2%, and 38.6%, respectively. A significantly higher mortality was observed in patients with higher tumour and TNM staging. CONCLUSIONS The survival throughout follow-up was higher in liver transplant, and tumour recurrence was more frequent in patients with partial surgical resection. The survival results in transplanted patients are consistent with the Spanish and European Liver Transplant Register and with the United Network for Organ Sharing register.
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Affiliation(s)
- Marlén Alvite Canosa
- Unidad de Cirugía Hepatobiliopancreática y Trasplante Hepático, Complejo Hospitalario Universitario de A Coruña, A Coruña, España.
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Application of tumor-node-metastasis staging 2002 version in locally advanced hepatocellular carcinoma: is it predictive of surgical outcome? BMC Cancer 2010; 10:535. [PMID: 20925965 PMCID: PMC2958946 DOI: 10.1186/1471-2407-10-535] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2010] [Accepted: 10/07/2010] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Locally advanced (pT3-4N0M0) hepatocellular carcinoma (HCC) is a heterogeneous group of tumors, which consists of four different categories, including HCC with "multiple tumors more than 5 cm", "major vascular invasion", "invasion of adjacent organs", and "perforation of visceral peritoneum". The aim of our study was to verify whether the 2002 version of the Tumor-Node-Metastasis staging system could predict surgical outcomes in patients with locally advanced HCC. METHODS We retrospectively reviewed 298 patients with pT3-4N0M0 HCC who underwent hepatic resection from 1993 to 2000 in an academic tertiary hospital. Overall survival (OS) and cumulative recurrence rate (CRR) of the four categories of locally advanced HCC patients were compared. RESULTS In multivariate analysis, major vascular invasion was identified as the most significant factor (HR = 3.291, 95% CI 2.362-4.584, P < 0.001) followed by cirrhosis status on OS, and was found to be the only independent factor of CRR (HR = 2.242, 95% CI 1.811-3.358, P < 0.001) in patients with locally advanced HCC. Among the four categories of locally advanced HCC, OS was significantly worse, and CRR was significantly higher in patients with HCC with major vascular invasion (pT3) than with multiple tumors more than 5 cm (pT3); or tumor invasion of adjacent organs (pT4); or perforation of visceral peritoneum (pT4). No significant differences were observed in OS or CRR between the latter three groups of patients. CONCLUSIONS HCC with major vascular invasion, which are classified as pT3 under the current TNM staging, have the worst prognosis when compared with the other categories of pT3-4 disease. There is a need to redefine the T classification and to stratify locally advanced HCC.
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Cheung TT, Ng KK, Chok KS, Chan SC, Poon RT, Lo CM, Fan ST. Combined resection and radiofrequency ablation for multifocal hepatocellular carcinoma: prognosis and outcomes. World J Gastroenterol 2010; 16:3056-3062. [PMID: 20572310 PMCID: PMC2890947 DOI: 10.3748/wjg.v16.i24.3056] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2010] [Revised: 03/12/2010] [Accepted: 03/19/2010] [Indexed: 02/06/2023] Open
Abstract
AIM To analyze the combined treatment of resection and intraoperative radiofrequency ablation (RFA) for multifocal hepatocellular carcinoma in terms of prognosis and surgical outcomes. METHODS This study was a retrospective case comparison study using prospectively collected data. The study covered the period from April 2001 to December 2006. The data of 200 patients with histologically confirmed hepatocellular carcinoma were reviewed. Nineteen patients (17 men and 2 women) having received resection in combination with RFA were chosen as subjects of the study (the combination group). Fifty-four patients (43 men and 11 women) having received resection alone were selected for comparison (the resection group). The two groups matched tumor number and tumor size, and all the patients in the two groups displayed no tumor rupture, major vascular involvement and distant metastasis. Their demographics, preoperative assessment, disease recurrence patterns, overall survival and disease-free survival were compared. RESULTS In the combination group, the median age was 65 years (range, 34-77 years), the median tumor number was 3 (range, 2-9), and the median tumor size was 6 cm (range, 1.2-14 cm). In the resection group, the median age was 51.5 years (range, 27-80 years, P = 0.003), the median tumor number was 3 (range, 2-9, P = 0.574), and the median tumor size was 6 cm (range, 1-14 cm, P = 0.782). The two groups were similar in characteristics of tumors and comorbidities, and had comparable results in preoperative liver function tests. All patients had Child-Pugh class A status. Bilobar involvement occurred in 14 patients (73.6%) in the combination group and 3 patients (5.5%) in the resection group (P = 0.04). Six patients (32%) in the combination group and 35 patients (65%) in the resection group underwent major hepatectomy. Thirteen patients (68%) in the combination group and 19 patients (35%) in the resection group underwent minor hepatectomy (P = 0.012). The combination group had fewer major resections (32% vs 65%, P = 0.012), less blood loss (400 vs 657 mL, P = 0.007), shorter operation time (270 vs 400 min, P = 0.001), and shorter hospital stay (7 vs 8.5 d, P = 0.042). The two groups displayed no major differences in surgical complications (15.8% vs 31.5%, P = 0.24), disease recurrence (63.2% vs 50%, P = 0.673), hospital mortality (5.3% vs 5.6%, P = 1), and overall survival (53 vs 44.5 mo, P = 0.496). CONCLUSION Safe and effective for selected patients with multifocal hepatocellular carcinoma, the combination of resection and intraoperative RFA widens the applicability of surgical intervention for the disease.
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An aggressive approach leads to improved survival in hepatocellular carcinoma patients with portal vein tumor thrombus. J Cancer Res Clin Oncol 2010; 137:139-49. [PMID: 20340033 PMCID: PMC3015200 DOI: 10.1007/s00432-010-0868-x] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2010] [Accepted: 03/09/2010] [Indexed: 02/06/2023]
Abstract
PURPOSE Many physicians express a relatively nihilistic approach to the treatment of hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). Consensus among surgeons regarding the indications for an aggressive approach has not been reached. Current study was aimed to determine whether an aggressive approach, with an extended resection with thrombectomy and adjuvant therapy, would lead to an improved survival for HCC patients with PVTT. METHODS A retrospective review of 116 HCC patients with PVTT admitted from 1996 to 2006 was conducted. Patients were divided into 2 time-period (TP) cohorts, of them, 51 cases in the first 5 years (TP1) and 65 in the last 5 years (TP2). RESULTS Surgical operations were performed on 68 patients. Twenty-one surgical resections were performed in TP1 and forty-seven in TP2. The extent of liver resections, as well as the frequency of thrombectomy, was greater in TP2 (P = 0.039). During both time-periods, an aggressive therapy was associated with improved survival (P < 0.02 TP1, P < 0.001 TP2). Overall survival of all patients in TP2 was significantly greater than in TP1 (P < 0.001), with a median survival of 15 months in TP2, whereas in TP1, the survival was only 9 months. The median 1-, 3-year survivals in TP2 (54 and 34%, respectively) were also greater than that in TP1 (31 and 7%, respectively). A multiple logistic regression analysis revealed that radical resection and adjuvant therapy were the independent predictors of overall survival. CONCLUSIONS An aggressive approach, combining extended liver resection with thrombectomy and adjuvant therapy, leads to an improved survival in the HCC patients with PVTT.
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Affiliation(s)
- Charles H Cha
- Surgical Oncology, Department of Surgery, Yale University School of Medicine, New Haven, Connecticut, USA
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Morris-Stiff G, Gomez D, de Liguori Carino N, Prasad K. Surgical management of hepatocellular carcinoma: Is the jury still out? Surg Oncol 2009; 18:298-321. [DOI: 10.1016/j.suronc.2008.08.003] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2008] [Accepted: 08/19/2008] [Indexed: 02/07/2023]
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Goldsmith PJ, Toogood GJ, Lodge JPA, Prasad KR. Salvage transplantation for stage IVa hepatocellular carcinoma, what are the guidelines? Clin Transplant 2009; 23:581. [DOI: 10.1111/j.1399-0012.2009.01039.x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Nodules less than 20 mm and vascular invasion are predictors of survival in small hepatocellular carcinoma. J Clin Gastroenterol 2009; 43:191-5. [PMID: 19142170 DOI: 10.1097/mcg.0b013e31817ff199] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND The aims of this study were to analyze the overall survival of patients with cirrhosis and small hepatocellular carcinoma (HCC) and identify independent pretreatment predictors of survival in Brazil. METHODS Between 1998 and 2003, 74 patients with cirrhosis and small HCC were evaluated. Predictors of survival were identified using the Kaplan-Meier survival curves and the Cox model. RESULTS The overall survival rates were 80%, 41%, and 17% at 12, 36, and 60 months, respectively. The mean length of follow-up after HCC diagnosis was 23 months (median 22 mo, range: 1 to 86 mo) for the entire group. Univariate analysis showed that model for endstage liver disease (MELD) score (P=0.016), Child-Pugh classification (P=0.007), alpha-fetoprotein level (P=0.006), number of nodules (P=0.041), tumor diameter (P=0.009), and vascular invasion (P<0.0001) were significant predictors of survival. Cox regression analysis identified vascular invasion (relative risk=14.60, confidence interval 95%=3.3-64.56, P<0.001) and tumor size >20 mm (relative risk=2.14, confidence interval 95%=1.07-4.2, P=0.030) as independent predictors of decreased survival. Treatment of HCC was related to increased overall survival. CONCLUSIONS Identification of HCC smaller than 20 mm is associated with longer survival. Presence of vascular invasion, even in small tumors, maybe associated with poor prognosis. Treatment of small tumors of up to 20 mm diameter is related to increased survival.
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Lin CY, Kee KM, Wang JH, Lee CM, Chen CL, Changchien CS, Hu TH, Cheng YF, Hsu HC, Wang CC, Chen TY, Lu SN. Is the Cancer of the Liver Italian Program system an adequate weighting for survival of hepatocellular carcinoma? Evaluation of intrascore prognostic value among 36 subgroups. Liver Int 2009; 29:74-81. [PMID: 18331238 DOI: 10.1111/j.1478-3231.2008.01702.x] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND The Cancer of the Liver Italian Program (CLIP) staging system for hepatocellular carcinoma (HCC) was subdivided into 36 subgroups. We aimed to validate the prognostic value of CLIP scoring. METHODS This study included 3868 HCC cases treated between 1986 and 2002. Survival and prognostic impact of all subgroups were analysed. RESULTS In primary CLIP, comparisons of each score showed a significant difference (P<0.001) and exhibited a linear trend (P<0.001). A CLIP score of 0 was used as control group. Portal vein thrombosis, Child-Pugh B, alpha-fetoprotein (AFP) > or =400 ng/ml and multinodular with tumour extension < or =50% of the four subgroups with a CLIP score of 1 exhibited decreasing univariate hazard ratios and 95% confidence intervals, with values of 2.99 (2.05-4.37), 2.39 (2.00-2.86), 1.66 (1.40-1.96) and 1.39 (1.18-1.63) respectively. Homogeneity in the same score was evaluated by comparing subgroup survival curves. For scores 1-5, 83.3% (5/6), 57.1% (16/28), 24.4% (11/45), 3.6% (1/28) and 16.7% (1/6) pairs of survival curves significantly differed, respectively, with decreasing linear trend (P<0.001). CONCLUSION Different prognostic weighting of four predictive factors caused intrascore heterogeneity. Lower CLIP scores were associated with increased differences in intrascore. In conclusion, the CLIP staging scoring system is a reasonable ordinal scale, but the clinician must be aware of the heterogeneity of mortality risk within a given score.
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Affiliation(s)
- Chih-Yun Lin
- Department of Internal Medicine, Division of Hepatogastroenterology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
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