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Aramaki O, Takayama T, Matsuyama Y, Kubo S, Kokudo N, Kurosaki M, Murakami T, Shiina S, Kudo M, Sakamoto M, Nakashima O, Fukumoto T, Iijima H, Eguchi S, Soejima Y, Makuuchi M. Reevaluation of Makuuchi's criteria for resecting hepatocellular carcinoma: A Japanese nationwide survey. Hepatol Res 2023; 53:127-134. [PMID: 36181504 DOI: 10.1111/hepr.13844] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Revised: 09/12/2022] [Accepted: 09/21/2022] [Indexed: 02/04/2023]
Abstract
AIM Although Makuuchi's criteria are widely used to determine the cut-off for safe liver resection, there have been few reports of concrete data supporting their validity. Here, we verified the utility of Makuuchi's criteria by comparing the operative mortality rates associated with liver resection between hepatocellular carcinoma (HCC) patients meeting or exceeding the criteria. METHODS A database was built using data from 15 597 patients treated between 2000 and 2007 for whom values for all three variables included in Makuuchi's criteria for liver resection (clinical ascites, serum bilirubin, and indocyanine green clearance) were available. The patients were divided into those fulfilling (n = 12 175) or exceeding (n = 3422) the criteria. The postoperative mortality (death for any reason within 30 days) and long-term survival were compared between the two groups. RESULTS The operative mortality rate was significantly lower in patients meeting the criteria than in those exceeding the criteria (1.07% vs. 2.01%, respectively; p < 0.001). On multivariate analysis, exceeded the criteria was significantly associated with the risk for operative mortality (relative risk 2.08; 95% confidence interval (CI), 1.23-3.52; p = 0.007). Surgical indication meeting or exceeding the criteria was an independent factor for overall survival (hazard ratio 1.27; 95% CI, 1.18-1.36; p < 0.001). CONCLUSION Makuuchi's criteria are suitable for determining the indication for resection of HCC due to the reduction in risk of operative mortality.
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Affiliation(s)
- Osamu Aramaki
- Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Tadatoshi Takayama
- Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan
| | | | - Shoji Kubo
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Norihiro Kokudo
- Department of Surgery, National Center for Global Health and Medicine, Tokyo, Japan
| | - Masayuki Kurosaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino, Japan
| | - Takamichi Murakami
- Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Shuichiro Shiina
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kinki University School of Medicine, Kobe, Japan
| | - Michiie Sakamoto
- Department of Pathology, Keio University School of Medicine, Tokyo, Japan
| | - Osamu Nakashima
- Laboratory Services Center, St. Mary's Hospital, Kurume, Japan
| | - Takumi Fukumoto
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Hiroko Iijima
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Hyogo College of Medicine, Nishinomiya, Japan
| | - Susumu Eguchi
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Yuji Soejima
- Department of Surgery, Division of Gastroenterological, Hapato-Biliary-Pancreatic, Transplantation, and Pediatric Surgery, Shinshu University School of Medicine, Matsumoto, Japan
| | - Masatoshi Makuuchi
- Department of Hepato-Biliary-Pancreatic Surgery, Japanese Red Cross Medical Center, Tokyo, Japan
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2
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Zhao L, Wang J, Kong J, Zheng X, Yu X. The impact of body mass index on short-term and long-term surgical outcomes of laparoscopic hepatectomy in liver carcinoma patients: a retrospective study. World J Surg Oncol 2022; 20:150. [PMID: 35538493 PMCID: PMC9087971 DOI: 10.1186/s12957-022-02614-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Accepted: 04/07/2022] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND It was generally accepted that obesity could increase the morbidity and mortality of surgical patients. However, the influence of body mass index (BMI) on short-term and long-term surgical outcomes of laparoscopic hepatectomy (LH) for patients with liver carcinoma remains unclear. The aim of this study was to evaluate the influence of BMI on surgical outcomes. METHODS From August 2003 to April 2016, 201 patients with liver carcinoma who underwent LH were enrolled in our study. Based on their BMI in line with the WHO's definition of obesity for the Asia-Pacific region, patients were divided into three groups: underweight (BMI< 18.5 kg/m2), normal weight (18.5≤BMI< 23 kg/m2), and overweight (BMI≥ 23 kg/m2). Demographics and surgical outcomes of laparoscopic hepatectomy were compared in different BMI stratification. We investigated overall survival and relapse-free survival across the BMI categories. RESULTS Of the 201 patients, 23 (11.44%) were underweight, 96 (47.76%) were normal weight, and 82 (40.80%) were overweight. The overall complication rate in the underweight group was much higher than that in the normal weight and overweight groups (p=0.048). Postoperative complications, underweight patients developed grade III or higher Clavien-Dindo classifications (p=0.042). Among the three BMI groups, there were no significant differences in overall and relapse-free survival with Kaplan-Meier analysis (p=0.104 and p=0.190, respectively). On the other hand, gender, age, liver cirrhosis, bile leak, ascites, and Clavien classification (III-IV) were not independent risk factors for overall and relapse-free survival in multivariable Cox proportional hazards models. CONCLUSIONS BMI status does not affect patients with liver carcinoma long-term surgical outcomes concerned to overall survival and relapse-free survival after laparoscopic hepatectomy. However, being underweight was associated with an increased perioperative complication rate, and perioperative careful monitoring might be required after hepatectomy for underweight with liver carcinoma.
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Affiliation(s)
- Lei Zhao
- Department of Anesthesiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, China
| | - Jiangang Wang
- Hangzhou Emergency Medical Center, Hangzhou, 310021, Zhejiang, China
| | - Jingxia Kong
- Department of Investment and Insurance, Zhejiang Financial College, Hangzhou, Zhejiang Province, China
| | - Xing Zheng
- Department of Anesthesiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, China
| | - Xin Yu
- Department of Anesthesiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, China.
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Sun B, Zhang W, Chen L, Sun T, Ren Y, Zhu L, Qian K, Zheng C. The safety and efficacy of percutaneous ethanol injection in the treatment of tumor thrombus in advanced hepatocellular carcinoma with portal vein tumor thrombus. Abdom Radiol (NY) 2022; 47:858-868. [PMID: 34820688 DOI: 10.1007/s00261-021-03349-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Revised: 11/08/2021] [Accepted: 11/09/2021] [Indexed: 11/28/2022]
Abstract
OBJECTIVES To compare the efficacy and safety of percutaneous ethanol injection (PEI) combined with transarterial chemoembolization (TACE + PEI) vs. TACE alone for the treatment of patients with advanced hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT). METHODS A total of 130 HCC patients with PVTT treated from May 2014 to August 2018 were retrospectively evaluated. Among them, 33 patients received TACE + PEI and 97 patients received TACE alone. PVTT was classified according to the Japanese Society of Hepatology; 97 patients had VP3 PVTT. Propensity score matching (PSM) was used to reduce selection bias. RESULTS Before PSM, the median overall survival (mOS) was 11 months (95% CI: 7.8-14.2) in the TACE + PEI group and 6 months (95% CI: 5.1-6.9) in the TACE group (p < 0.001), and the median progression-free survival (mPFS) was 5 months (95% CI: 3.7-6.3) in the TACE + PEI group and 2.5 months (95% CI: 2.1-2.9) in the TACE group (p < 0.001). Similar results were seen after PSM. Subgroup analysis showed that in patients with tumors > 5 cm in diameter and the VP3 subgroup, TACE + PEI brought a significant survival advantage over TACE alone before and after PSM. In the adverse event analysis, severe abdominal pain and bleeding after operation were seen in more patients in the TACE + PEI group than in the TACE group before PSM (P < 0.05). CONCLUSIONS For HCC patients with PVTT (especially those with tumor diameters > 5 cm and grade VP3), TACE combined with PEI for HCC patients with PVTT is safe and may provide better survival outcomes.
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Affiliation(s)
- Bo Sun
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China
- Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Weihua Zhang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China
- Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Lei Chen
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China
- Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Tao Sun
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China
- Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Yanqiao Ren
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China
- Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Licheng Zhu
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China
- Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Kun Qian
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China.
- Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
| | - Chuansheng Zheng
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China.
- Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
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Ma X, Mo M, Tan C, Tan JHJ, Huang H, Liu B, Huang D, Liu S, Zeng X, Qiu X. Liver-specific LINC01146, a promising prognostic indicator, inhibits the malignant phenotype of hepatocellular carcinoma cells both in vitro and in vivo. J Transl Med 2022; 20:57. [PMID: 35101062 PMCID: PMC8802422 DOI: 10.1186/s12967-021-03225-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Accepted: 12/29/2021] [Indexed: 01/27/2023] Open
Abstract
Abstract
Background
Long non-coding RNAs (lncRNAs) are involved in the development of hepatocellular carcinoma (HCC). We aimed to investigate the function of LINC01146 in HCC.
Methods
The expression of LINC01146 in HCC tissues was explored via The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and was verified using quantitative real-time polymerase chain reaction (qRT–PCR) in our HCC cohort. Kaplan–Meier analysis was used to assess the relationship between LINC01146 and the prognosis of HCC patients. Cell Counting Kit 8, colony formation assays, Transwell assays, flow cytometric assays, and tumour formation models in nude mice were conducted to reveal the effects of LINC01146 on HCC cells both in vitro and in vivo. Bioinformatic methods were used to explore the possible potential pathways of LINC01146 in HCC.
Results
LINC01146 was significantly decreased in HCC tissues compared with adjacent normal tissues and was found to be related to the clinical presentations of malignancy and the poor prognosis of HCC patients. Overexpression of LINC01146 inhibited the proliferation, migration, and invasion of HCC cells in vitro, while promoting their apoptosis. In contrast, downregulation of LINC01146 exerted the opposite effects on HCC cells in vitro. In addition, overexpression of LINC01146 significantly inhibited tumour growth, while downregulation of LINC01146 promoted tumour growth in vivo. Furthermore, the coexpressed genes of LINC01146 were mainly involved in the “metabolic pathway” and “complement and coagulation cascade pathway”.
Conclusion
LINC01146 expression was found to be decreased in HCC tissues and associated with the prognosis of HCC patients. It may serve as a cancer suppressor and prognostic biomarker in HCC.
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Božin T, Mustapić S, Bokun T, Patrlj L, Rakić M, Aralica G, Kujundžić M, Trkulja V, Grgurević I. Albi Score as a Predictor of Survival in Patients with Compensated Cirrhosis Resected for Hepatocellular Carcinoma: Exploratory Evaluation in Relationship to Palbi and Meld Liver Function Scores. Acta Clin Croat 2019; 57:292-300. [PMID: 30431722 PMCID: PMC6531997 DOI: 10.20471/acc.2018.57.02.09] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023] Open
Abstract
The aim of the study was to explore predictive value of the ALBI, PALBI and MELD scores on survival in patients resected for hepatocellular carcinoma with compensated liver cirrhosis and no macrovascular infiltration. In this retrospective study, longitudinal survival analysis was performed. We analyzed patient/tumor characteristics and MELD, ALBI and PALBI scores as liver function tests for predicting survival outcome. Survival was analyzed from the date of liver resection until death, liver transplantation, or end of follow-up. Patients were stratified for age, cirrhosis etiology, presence of esophageal varices, hepatocellular carcinoma stage, microvascular invasion, histologic differentiation, and resection margins. We identified 38 patients (alcoholic cirrhosis in 84.2% of patients) resected over an 8-year period. Median preoperative MELD score was 8, ALBI score -2.63, and PALBI score -2.38. During the follow-up period, 24 patients died. Estimated median survival time was 36 months. Microvascular invasion was observed in 33 patients. Higher ALBI score was associated with 23.1% higher relative risk of death. PALBI score was associated with 12.1% higher relative risk of death, whereas MELD score was not associated with the risk of death. In conclusion, ALBI score demonstrated significant predictive capabilities for survival in patients with compensated cirrhosis resected for hepatocellular carcinoma.
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Affiliation(s)
| | - Sanda Mustapić
- Department of Gastroenterology, Hepatology and Clinical Nutrition, Dubrava University Hospital, Zagreb, Croatia
| | - Tomislav Bokun
- Department of Gastroenterology, Hepatology and Clinical Nutrition, Dubrava University Hospital, Zagreb, Croatia
| | - Leonardo Patrlj
- Department of Abdominal Surgery, Dubrava University Hospital, Zagreb, Croatia.,University of Zagreb, School of Medicine, Zagreb, Croatia
| | - Mislav Rakić
- Department of Abdominal Surgery, Dubrava University Hospital, Zagreb, Croatia
| | - Gorana Aralica
- University of Zagreb, School of Medicine, Zagreb, Croatia.,Department of Pathology, Dubrava University Hospital, Zagreb, Croatia
| | - Milan Kujundžić
- Department of Gastroenterology, Hepatology and Clinical Nutrition, Dubrava University Hospital, Zagreb, Croatia.,University of Zagreb, School of Medicine, Zagreb, Croatia
| | - Vladimir Trkulja
- Department of Pharmacology, University of Zagreb, School of Medicine, Zagreb, Croatia
| | - Ivica Grgurević
- Department of Gastroenterology, Hepatology and Clinical Nutrition, Dubrava University Hospital, Zagreb, Croatia.,University of Zagreb, School of Medicine, Zagreb, Croatia
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Lv Y, Wei W, Huang Z, Chen Z, Fang Y, Pan L, Han X, Xu Z. Long non-coding RNA expression profile can predict early recurrence in hepatocellular carcinoma after curative resection. Hepatol Res 2018; 48:1140-1148. [PMID: 29924905 DOI: 10.1111/hepr.13220] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2018] [Revised: 05/21/2018] [Accepted: 06/11/2018] [Indexed: 12/19/2022]
Abstract
AIM The aim of this study was to develop a novel long non-coding RNA (lncRNA) expression signature to accurately predict early recurrence for patients with hepatocellular carcinoma (HCC) after curative resection. METHODS Using expression profiles downloaded from The Cancer Genome Atlas database, we identified multiple lncRNAs with differential expression between early recurrence (ER) and non-early recurrence (non-ER) groups of patients with HCC. Least absolute shrinkage and selection operator for logistic regression models were used to develop an lncRNA-based classifier for predicting ER in the training set. An independent test set was used to validate the predictive value of this classifier. Furthermore, a co-expression network based on these lncRNAs and its highly related genes was constructed and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of genes in the network were carried out. RESULTS We identified 10 differentially expressed lncRNAs, including three that were upregulated and seven that were downregulated in the ER group. The lncRNA-based classifier was constructed based on seven lncRNAs (AL035661.1, PART1, AC011632.1, AC109588.1, AL365361.1, LINC00861, and LINC02084), and its accuracy was 0.83 in the training set, 0.87 in the test set, and 0.84 in the total set. Receiver operating characteristic curve analysis showed the area under the curve was 0.741 in the training set, 0.824 in the test set, and 0.765 in the total set. A functional enrichment analysis suggested that the genes highly related to four lncRNAs are involved in the immune system. CONCLUSION The expression profile of seven lncRNAs can effectively predict ER after surgical resection for HCC.
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Affiliation(s)
- Yufeng Lv
- Department of Medical Oncology, Affiliated Langdong Hospital of Guangxi Medical University, Nanning, China
| | - Wenhao Wei
- Department of Medical Oncology, Affiliated Langdong Hospital of Guangxi Medical University, Nanning, China
| | - Zhong Huang
- Department of Medical Oncology, Affiliated Langdong Hospital of Guangxi Medical University, Nanning, China
| | - Zhichao Chen
- Department of Medical Oncology, Affiliated Langdong Hospital of Guangxi Medical University, Nanning, China
| | - Yuan Fang
- Department of Medical Oncology, Affiliated Langdong Hospital of Guangxi Medical University, Nanning, China
| | - Lili Pan
- Department of Medical Oncology, Affiliated Langdong Hospital of Guangxi Medical University, Nanning, China
| | - Xueqiong Han
- Department of Medical Oncology, The First People's Hospital of Nanning, Nanning, China
| | - Zihai Xu
- Department of Medical Oncology, Affiliated Langdong Hospital of Guangxi Medical University, Nanning, China
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Lin CW, Chen YS, Lin CC, Lee PH, Lo GH, Hsu CC, Hsieh PM, Koh KW, Bair MJ, Dai CY, Huang JF, Chuang WL, Chen YL, Yu ML. Significant predictors of overall survival in patients with hepatocellular carcinoma after surgical resection. PLoS One 2018; 13:e0202650. [PMID: 30180193 PMCID: PMC6122804 DOI: 10.1371/journal.pone.0202650] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2018] [Accepted: 08/07/2018] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND The predictive factors of overall survival after hepatectomy for HCC remain controversial and need to be investigated. METHODS In total, 535 consecutive HCC patients undergoing resection were included and their clinicopathological data and overall survival were recorded. Both the tumor and adjacent non-tumor (ANT) tissues were subjected to immunohistochemistry analysis for the expression of autophagy-related markers. RESULTS Death was observed for 219 patients, and the cumulative overall survival rates at 1, 3, 5 and 7 years were 91.0%, 72.3%, 58.8%, and 27.7%, respectively. In the multivariate analysis, mortality was significantly associated with the following: diminished LC3 expression in both the tumor and ANT tissues, in the HCC tissues alone and in the ANT tissues alone (hazard ratio/95% confidence interval: 6.74/2.052-22.19, 6.70/1.321-33.98 and 2.58/1.499-4.915, respectively); recurrent HCC (5.11/3.136-8.342); HBV infection (2.75/1.574-4.784); cirrhosis (1.78/1.059-2.974); and antiviral therapy (0.42/0.250-0.697). The 5-year overall survival rates were 70.2%, 57.3%, 49.6% and 10.7% for patients with positive LC3 expression in both tissue types, in the HCC tissues alone, in the ANT tissues alone, and in neither tissue type, respectively. The 5-year overall survival rates were 56.7%, 47.3%, 51.2% and 38.7% for patients with HBV-related HCC, cirrhosis, no antiviral therapy, and recurrent HCC, respectively, and these rates were significantly lower than those in their counterparts. CONCLUSIONS Patients with recurrent HCC, HBV-related HCC, cirrhosis, and the absence of antiviral therapy showed significantly lower overall survival rates. Furthermore, LC3 expression in both the tumor and liver microenvironments were significantly predictive of overall survival after resection for HCC.
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MESH Headings
- Adult
- Aged
- Antiviral Agents/therapeutic use
- Biomarkers, Tumor/genetics
- Biomarkers, Tumor/metabolism
- Carcinoma, Hepatocellular/drug therapy
- Carcinoma, Hepatocellular/etiology
- Carcinoma, Hepatocellular/mortality
- Carcinoma, Hepatocellular/pathology
- Confidence Intervals
- Female
- Hepatectomy
- Hepatitis B/complications
- Hepatitis B/drug therapy
- Hepatitis B/mortality
- Hepatitis B/pathology
- Humans
- Liver Cirrhosis/drug therapy
- Liver Cirrhosis/mortality
- Liver Cirrhosis/pathology
- Liver Cirrhosis/surgery
- Liver Neoplasms/drug therapy
- Liver Neoplasms/etiology
- Liver Neoplasms/mortality
- Liver Neoplasms/pathology
- Male
- Microtubule-Associated Proteins/genetics
- Microtubule-Associated Proteins/metabolism
- Middle Aged
- Multivariate Analysis
- Neoplasm Recurrence, Local/drug therapy
- Neoplasm Recurrence, Local/mortality
- Neoplasm Recurrence, Local/pathology
- Neoplasm Recurrence, Local/surgery
- Prognosis
- Survival Rate
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Affiliation(s)
- Chih-Wen Lin
- Division of Gastroenterology and Hepatology, E-Da Dachang Hospital, I-Shou University, Kaohsiung, Taiwan
- Division of Gastroenterology and Hepatology, Department of Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
- Health Examination Center, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan
- * E-mail:
| | - Yaw-Sen Chen
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan
- Department of Surgery, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
| | - Chih-Che Lin
- Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Po-Huang Lee
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan
- Department of Surgery, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
| | - Gin-Ho Lo
- Division of Gastroenterology and Hepatology, Department of Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Chia-Chang Hsu
- Health Examination Center, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
| | - Pei-Min Hsieh
- Department of Surgery, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
| | - Kah Wee Koh
- Division of Gastroenterology and Hepatology, Department of Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
- Health Examination Center, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
| | - Ming-Jong Bair
- Division of Gastroenterology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, and Mackay Medical College, New Taipei City, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Yao-Li Chen
- Division of General Surgery, Department of Surgery, Changhua Christian Hospital, Changhua, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- College of Biological Science and Technology, National Chiao Tung University, Hsin-Chu, Taiwan
- Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan
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8
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Liu S, Miao C, Liu J, Wang C, Lu X. Four differentially methylated gene pairs to predict the prognosis for early stage hepatocellular carcinoma patients. J Cell Physiol 2018; 233:6583-6590. [DOI: 10.1002/jcp.26256] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2017] [Accepted: 11/07/2017] [Indexed: 02/03/2023]
Affiliation(s)
- Shaoguang Liu
- Department of Emergency SurgeryGansu Provincial HospitalGansuChina
| | - Changfeng Miao
- Department of General SurgeryGansu Provincial HospitalGansuChina
| | - Juan Liu
- Operating Room, Huai'an Second People's HospitalThe Affiliated Huai'an Hospital of Xuzhou Medical UniversityHuai'anChina
| | - Chang‐Cheng Wang
- Department of GastroenterologyHuai'an Second People's Hospital and The Affiliated Huai'an Hospital of Xuzhou Medical UniversityHuai'anJiangsuChina
| | - Xiao‐Jie Lu
- Liver Transplantation CenterThe First Affiliated Hospital of Nanjing Medical UniversityNanjingChina
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9
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Yang B, Li CL, Guo WH, Qin TQ, Jiao H, Fei ZJ, Zhou X, Duan LJ, Liao ZY. Intra-arterial ethanol embolization augments response to TACE for treatment of HCC with portal venous tumor thrombus. BMC Cancer 2018; 18:101. [PMID: 29378532 PMCID: PMC5789611 DOI: 10.1186/s12885-018-3989-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2017] [Accepted: 01/15/2018] [Indexed: 02/07/2023] Open
Abstract
Background The prognosis of hepatocellular carcinoma with portal vein tumor thrombus remains extremely poor. This pilot study aimed to evaluate the technical feasibility, effectiveness and safety of transcatheter chemoembolization for tumors in the liver parenchyma plus intra-arterial ethanol embolization for portal vein tumor thrombus. Methods A pilot study was carried out on 31 patients in the treatment group (transcatheter chemoembolization plus intra-arterial ethanol embolization) and 57 patients in the control group (transcatheter chemoembolization alone). Enhanced computed tomography/magnetic resonance images were repeated 4 weeks after the procedure to assess the response. Overall survival and complications were assessed until the patient died or was lost to follow-up. Results Median survival was 10.5 months in the treatment group (2.4 ± 1.7 courses) and 3.9 months in the control group (1.9 ± 1 courses) (P = 0.001). Patients in the treatment group had better overall survival (at 3, 6 and 12 months, respectively), compared to patients in the control group (90.3% vs. 59.6%, 64.5% vs. 29.8%, and 41.9% vs. 10.6%; p = 0.001). Furthermore, the rate of portal vein tumor thrombus regression was higher in the treatment group (93.1%) than in the control group (32.1%) (P < 0.001). Conclusions Based on the results of this study, transcatheter chemoembolization combined with intra-arterial ethanol embolization may be more effective than transcatheter chemoembolization alone for treating hepatocellular carcinoma with portal vein tumor thrombus. Intra-arterial ethanol embolization for treating portal vein tumor thrombus is safe, feasible and prolongs overall survival.
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Affiliation(s)
- Biao Yang
- Department of Abdominal Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Guoxue Lane No. 37, Chengdu, Sichuan Province, 610041, People's Republic of China
| | - Chun-Lin Li
- Department of Abdominal Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Guoxue Lane No. 37, Chengdu, Sichuan Province, 610041, People's Republic of China
| | - Wen-Hao Guo
- Department of Abdominal Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Guoxue Lane No. 37, Chengdu, Sichuan Province, 610041, People's Republic of China
| | - Tian-Qiang Qin
- Chinese Evidence-Based Medicine Centre, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China
| | - He Jiao
- Department of Radiology, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China
| | - Ze-Jun Fei
- Department of Radiology, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China
| | - Xuan Zhou
- Department of Radiology, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China
| | - Lin-Jia Duan
- Department of Radiology, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China
| | - Zheng-Yin Liao
- Department of Abdominal Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Guoxue Lane No. 37, Chengdu, Sichuan Province, 610041, People's Republic of China.
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Ao L, Song X, Li X, Tong M, Guo Y, Li J, Li H, Cai H, Li M, Guan Q, Yan H, Guo Z. An individualized prognostic signature and multi‑omics distinction for early stage hepatocellular carcinoma patients with surgical resection. Oncotarget 2018; 7:24097-110. [PMID: 27006471 PMCID: PMC5029687 DOI: 10.18632/oncotarget.8212] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2015] [Accepted: 03/02/2016] [Indexed: 12/31/2022] Open
Abstract
Previously reported prognostic signatures for predicting the prognoses of postsurgical hepatocellular carcinoma (HCC) patients are commonly based on predefined risk scores, which are hardly applicable to samples measured by different laboratories. To solve this problem, using gene expression profiles of 170 stage I/II HCC samples, we identified a prognostic signature consisting of 20 gene pairs whose within-sample relative expression orderings (REOs) could robustly predict the disease-free survival and overall survival of HCC patients. This REOs-based prognostic signature was validated in two independent datasets. Functional enrichment analysis showed that the patients with high-risk of recurrence were characterized by the activations of pathways related to cell proliferation and tumor microenvironment, whereas the low-risk patients were characterized by the activations of various metabolism pathways. We further investigated the distinct epigenomic and genomic characteristics of the two prognostic groups using The Cancer Genome Atlas samples with multi-omics data. Epigenetic analysis showed that the transcriptional differences between the two prognostic groups were significantly concordant with DNA methylation alternations. The signaling network analysis identified several key genes (e.g. TP53, MYC) with epigenomic or genomic alternations driving poor prognoses of HCC patients. These results help us understand the multi-omics mechanisms determining the outcomes of HCC patients.
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Affiliation(s)
- Lu Ao
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150086, China.,Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Department of Bioinformatics, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350001, China
| | - Xuekun Song
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150086, China
| | - Xiangyu Li
- Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Department of Bioinformatics, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350001, China
| | - Mengsha Tong
- Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Department of Bioinformatics, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350001, China
| | - You Guo
- Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Department of Bioinformatics, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350001, China
| | - Jing Li
- Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Department of Bioinformatics, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350001, China
| | - Hongdong Li
- Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Department of Bioinformatics, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350001, China
| | - Hao Cai
- Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Department of Bioinformatics, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350001, China
| | - Mengyao Li
- Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Department of Bioinformatics, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350001, China
| | - Qingzhou Guan
- Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Department of Bioinformatics, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350001, China
| | - Haidan Yan
- Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Department of Bioinformatics, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350001, China
| | - Zheng Guo
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150086, China.,Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Department of Bioinformatics, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350001, China
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11
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Hepatocellular carcinoma biology predicts survival outcome after liver transplantation in the USA. Indian J Gastroenterol 2017; 36:117-125. [PMID: 28194604 DOI: 10.1007/s12664-017-0732-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2016] [Accepted: 01/20/2017] [Indexed: 02/04/2023]
Abstract
PURPOSE The aim of this study is to evaluate the clinicopathologic prognostic factors of cancer-specific survival (CSS) in hepatocellular carcinoma (HCC) patients who underwent liver transplantation (LT) stratified by tumor size. METHODS From the Surveillance, Epidemiology, and End Results (SEER) 18 registries (2004-2012), we retrieved data of 570 patients who underwent LT for a solitary primary HCC lesion ≤5 cm. A two multivariable Cox models were constructed to identify prognostic factors of CSS in a two different tumor sizes (2 cm cutoff). RESULTS Out of 570 HCC patients (median age 57 years), 16% had microvascular invasion (MVI) and 12% had a poorly differentiated tumor. Male sex (odds ratio [OR] 2.6), tumor size >2 cm (OR 1.78), elevated AFP (OR 2.31), and poor tumor differentiation (OR 2.59) are significant predictors of MVI. With a median follow up of 41.5 months (range 1-107 months), the 5-year CSS rate was 90% in the absence of MVI compared to 75% in the presence of MVI (p<0.001). Multivariate models revealed that age ≥60 years (hazard ratio [HR] 2.08), MVI (HR 2.26), and poor tumor differentiation (HR 2.42), were significant risk factors of a dismal CSS with HCC size >2 cm, but not with HCC ≤2 cm. CONCLUSIONS Primary HCC tumor size ≤2 cm had an excellent prognosis after LT and was not affect by the presence of MVI or poor tumor differentiation.
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12
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Yang B, You X, Yuan ML, Qin TQ, Duan LJ, He J, Fei ZJ, Zhou X, Zan RY, Liao ZY. Transarterial Ethanol Ablation Combined with Transarterial Chemoembolization for Hepatocellular Carcinoma with Portal Vein Tumor Thrombus. HEPATITIS MONTHLY 2016; 16:e37584. [PMID: 27799963 PMCID: PMC5075224 DOI: 10.5812/hepatmon.37584] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/04/2016] [Revised: 05/23/2016] [Accepted: 06/19/2016] [Indexed: 02/05/2023]
Abstract
BACKGROUND The prognosis for hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is extremely poor. OBJECTIVES This study aimed to evaluate the safety and effectiveness of transarterial ethanol ablation (TEA) for the treatment of HCC with PVTT. METHODS Patients were treated with TEA for PVTT under cone-beam computed tomography and traditional transarterial chemoembolization (TACE) with epirubicin for intrahepatic lesions. RESULTS Seventeen men were successfully treated with TACE plus TEA. The mean overall survival was 18.3 ± 9.0 months (95% CI: 13.7 - 3.0 months). The quality of life (QoL) score increased from 56.9 ± 15.7 before the procedure to 88.5 ± 11.7 at 4 weeks after the procedure. Lipiodol accumulation grades of 3, 2, 1, and 0 were obtained in 3 (17.6%), 8 (47.1%), 6 (35.3%), and 0 (0%) patients, respectively. CONCLUSIONS TEA is a safe and effective method for treating patients with PVTT, offering advantages for QoL, response rate after TEA, and OS.
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Affiliation(s)
- Biao Yang
- Department of Abdominal Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
| | - Xin You
- Department of Abdominal Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
| | - Min lan Yuan
- Psychiatry Centre, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
| | - Tian Qiang Qin
- Chinese Evidence-Based Medicine Centre, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
| | - Lin Jia Duan
- Department of Radiology, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
| | - Jiao He
- Department of Radiology, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
| | - Ze Jun Fei
- Department of Radiology, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
| | - Xuan Zhou
- Department of Radiology, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
| | - Rui Yu Zan
- Department of Abdominal Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
| | - Zheng Yin Liao
- Department of Abdominal Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
- Corresponding Author: Zheng Yin Liao, Department of Abdominal Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China. Tel: +86-13981717611, E-mail:
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13
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Chiu CC, Wang JJ, Chen YS, Chen JJ, Tsai TC, Lai CC, Sun DP, Shi HY. Trends and predictors of outcomes after surgery for hepatocellular carcinoma: A nationwide population-based study in Taiwan. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2015; 41:1170-8. [PMID: 26048295 DOI: 10.1016/j.ejso.2015.04.023] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2014] [Revised: 04/19/2015] [Accepted: 04/27/2015] [Indexed: 02/07/2023]
Abstract
BACKGROUND Despite the huge and growing global burden of hepatocellular carcinoma (HCC), high-quality population-based studies of HCC prevalence and outcomes are scarce. PURPOSE To analyze trends and predictors of hospital resource utilization and mortality rates in a population of patients who had received HCC surgery. PATIENTS AND MATERIALS This population-based patient cohort study retrospectively analyzed 23,107 patients who had received surgical treatment for HCC from 1998 to 2009. RESULTS The prevalence rate of surgical treatment in HCC patients significantly increased by 167.4% from 4.857 per 100,000 persons in 1998 to 12.989 per 100,000 persons in 2009 (P < 0.001). Age, gender, Deyo-Charlson co-morbidity index score, hospital volume, surgeon volume, digestive system disease, hepatitis type and liver cirrhosis were significantly associated with HCC surgical outcomes (P < 0.05). Over the 12-year period analyzed, the estimated mean hospital treatment cost increased 9.4% whereas mean length of stay (LOS) decreased 25.3%. The estimated mean overall survival time after HCC surgery was 40.9 months (SD 1.2 months), and the overall in-hospital 1-, 3-, and 5-year survival rates were 97.2%, 79.9%, 61.1%, and 54.6%, respectively. CONCLUSIONS These population-based data reveal that the prevalence of HCC has increased, especially in older patients. Additionally, hospital treatment costs for HCC have increased despite decreases in LOS. These analytical results should be applicable to most countries with relatively small populations. Additionally, healthcare providers and patients should recognize that attributes of both the patient and the hospital may affect outcomes.
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Affiliation(s)
- C-C Chiu
- Department of General Surgery, Chi Mei Medical Center, Tainan and Liouying, Taiwan; Department of Electrical Engineering, Southern Taiwan University of Science and Technology, Tainan, Taiwan
| | - J-J Wang
- Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan
| | - Y-S Chen
- Department of Surgery, E-Da Hospital, Kaohsiung, Taiwan
| | - J-J Chen
- Department of Gastroenterology & Hepatology, Chi Mei Medical Center, Tainan and Liouying, Taiwan
| | - T-C Tsai
- Department of General Surgery, Chi Mei Medical Center, Tainan and Liouying, Taiwan
| | - C-C Lai
- Department of Intensive Care Medicine, Chi Mei Medical Center, Tainan and Liouying, Taiwan
| | - D-P Sun
- Department of General Surgery, Chi Mei Medical Center, Tainan and Liouying, Taiwan
| | - H-Y Shi
- Department of Healthcare Administration and Medical Informatics, Kaohsiung Medical University, Kaohsiung, Taiwan.
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Song P, Inagaki Y, Wang Z, Hasegawa K, Sakamoto Y, Arita J, Tang W, Kokudo N. High Levels of Gamma-Glutamyl Transferase and Indocyanine Green Retention Rate at 15 min as Preoperative Predictors of Tumor Recurrence in Patients With Hepatocellular Carcinoma. Medicine (Baltimore) 2015; 94:e810. [PMID: 26020384 PMCID: PMC4616400 DOI: 10.1097/md.0000000000000810] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2015] [Accepted: 04/02/2015] [Indexed: 02/06/2023] Open
Abstract
This study investigated the preoperative independent risk factors associated with survival and recurrence for patients with hepatocellular carcinoma (HCC) who underwent hepatic resection. In total, 384 consecutive patients who underwent curative hepatic resection for single primary HCC were studied. Predictive factors associated with 1-, 3-, and 5-year survival and recurrence-free survival (RFS) were assessed using a univariate log-rank test and multivariate Cox proportional hazards regression model. Gamma-glutamyl transferase (GGT) > 100 U/L was identified as a preoperative independent risk factor affecting 1-, 3-, and 5-year survival whereas GGT > 50 U/L and indocyanine green retention 15 min (ICG-R15) > 10% were identified as preoperative independent risk factors affecting 1-, 3-, and 5-year RFS. The 384 patients studied had a 1-, 3-, and 5-year RFS rate of 72.8%, 43.3%, and 27%, respectively. Patients with GGT > 50 U/L had a 1-, 3-, and 5-year RFS rate of 64.5%, 36.0%, and 21.7%. These patients had lower survival rates than did patients with GGT ≤ 50 U/L (P < 0.05). Patients with GGT > 50 U/L and ICG-R15 > 10% had a 1-, 3-, and 5-year RFS rate of 62.4%, 29.5%, and 14.1%, respectively. These patients had lower survival rates than did patients in the other 2 groups with different levels of GGT and ICG (P < 0.05, respectively). The same was also true for patients with a tumor < 5 cm in size. Combined information in the form of high levels of GGT and ICG-R15 is a preoperative predictor that warrants full attention when evaluating tumor recurrence postoperatively.
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Affiliation(s)
- Peipei Song
- From the Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
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15
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Pesi B, Ferrero A, Grazi GL, Cescon M, Russolillo N, Leo F, Boni L, Pinna AD, Capussotti L, Batignani G. Liver resection with thrombectomy as a treatment of hepatocellular carcinoma with major vascular invasion: results from a retrospective multicentric study. Am J Surg 2015; 210:35-44. [PMID: 25935229 DOI: 10.1016/j.amjsurg.2014.09.041] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2014] [Revised: 09/09/2014] [Accepted: 09/15/2014] [Indexed: 12/13/2022]
Abstract
BACKGROUND The role of liver resection (LR) of hepatocellular carcinoma with macroscopic vascular thrombosis (MVT) remains controversial. The aim of this study is to evaluate whether the presence of MVT should still be considered a contraindication for LR. METHODS Retrospective study was carried out on 62 patients who underwent LR and thrombectomy for hepatocellular carcinoma complicated by MVT. Of the 62 patients, 15 (36.5%) had tumor thrombus (TT) in the peripheral portal vein (Vp1), 5 (12.2%) in second branch (Vp2), and 21 (51.3%) in the first branch/portal vein trunk (Vp3), while on the hepatic/cava vein side, 8 (12.9%) had TT in the main trunk of the hepatic veins (Vv2) and 3 (4.8%) had TT reaching the vena cava/right atrium (Vv3). RESULTS Perioperative major morbidity was 14.5%, while in-hospital mortality was 4.8%. Overall, 1, 3, and 5-year survival rates were 53.3%, 30.1%, and 20%, and disease-free survival rates were 31.7%, 20.8%, and 15.6%, respectively. There were no differences in survival about the MVT localized in Vp1, Vp2, or Vp3 (P = .77), while we found a statistical trend between patients with Vv2 and Vv3 (P = .06). CONCLUSION Surgical resection seems to be justified in these patients, and the presence of MVT should no longer be considered an absolute contraindication for LR.
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Affiliation(s)
- Benedetta Pesi
- Gastrointestinal Surgery Unit, Department of Surgery and Translational Medicine, Careggi University Hospital, Largo Brambilla 3, Florence 50134, Italy
| | - Alessandro Ferrero
- Department of HPB and Digestive Surgery, Mauriziano Umberto I Hospital, Turin, Italy
| | - Gianluca L Grazi
- Liver Surgery and Transplantation Unit, Department of Emergency, Surgery and Transplants, S. Orsola-Malpighi University Hospital, Bologna, Italy
| | - Matteo Cescon
- Liver Surgery and Transplantation Unit, Department of Emergency, Surgery and Transplants, S. Orsola-Malpighi University Hospital, Bologna, Italy
| | - Nadia Russolillo
- Department of HPB and Digestive Surgery, Mauriziano Umberto I Hospital, Turin, Italy
| | - Francesca Leo
- Gastrointestinal Surgery Unit, Department of Surgery and Translational Medicine, Careggi University Hospital, Largo Brambilla 3, Florence 50134, Italy
| | - Luca Boni
- Department of Oncology/Core Research Laboratory, Careggi University Hospital, Florence, Italy
| | - Antonio D Pinna
- Liver Surgery and Transplantation Unit, Department of Emergency, Surgery and Transplants, S. Orsola-Malpighi University Hospital, Bologna, Italy
| | - Lorenzo Capussotti
- Department of HPB and Digestive Surgery, Mauriziano Umberto I Hospital, Turin, Italy
| | - Giacomo Batignani
- Gastrointestinal Surgery Unit, Department of Surgery and Translational Medicine, Careggi University Hospital, Largo Brambilla 3, Florence 50134, Italy.
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Wei CK, Tsai SJ, Yin WY, Chang CM, Chiou WY, Lee MS, Su YC, Lin HY, Hung SK. Treatment results and prognostic factors in resectable hepatocellular carcinoma—Results from a local general hospital. Tzu Chi Med J 2014. [DOI: 10.1016/j.tcmj.2014.06.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
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Feng K, Ma KS. Value of radiofrequency ablation in the treatment of hepatocellular carcinoma. World J Gastroenterol 2014; 20:5987-98. [PMID: 24876721 PMCID: PMC4033438 DOI: 10.3748/wjg.v20.i20.5987] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2013] [Revised: 02/21/2014] [Accepted: 04/01/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a malignant disease that substantially affects public health worldwide. It is especially prevalent in east Asia and sub-Saharan Africa, where the main etiology is the endemic status of chronic hepatitis B. Effective treatments with curative intent for early HCC include liver transplantation, liver resection (LR), and radiofrequency ablation (RFA). RFA has become the most widely used local thermal ablation method in recent years because of its technical ease, safety, satisfactory local tumor control, and minimally invasive nature. This technique has also emerged as an important treatment strategy for HCC in recent years. RFA, liver transplantation, and hepatectomy can be complementary to one another in the treatment of HCC, and the outcome benefits have been demonstrated by numerous clinical studies. As a pretransplantation bridge therapy, RFA extends the average waiting time without increasing the risk of dropout or death. In contrast to LR, RFA causes almost no intra-abdominal adhesion, thus producing favorable conditions for subsequent liver transplantation. Many studies have demonstrated mutual interactions between RFA and hepatectomy, effectively expanding the operative indications for patients with HCC and enhancing the efficacy of these approaches. However, treated tumor tissue remains within the body after RFA, and residual tumors or satellite nodules can limit the effectiveness of this treatment. Therefore, future research should focus on this issue.
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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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Choi SH, Choi GH, Kim SU, Park JY, Joo DJ, Ju MK, Kim MS, Choi JS, Han KH, Kim SI. Role of surgical resection for multiple hepatocellular carcinomas. World J Gastroenterol 2013; 19:366-74. [PMID: 23372359 PMCID: PMC3554821 DOI: 10.3748/wjg.v19.i3.366] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2012] [Revised: 12/03/2012] [Accepted: 12/15/2012] [Indexed: 02/06/2023] Open
Abstract
AIM: To clarify the role of surgical resection for multiple hepatocellular carcinomas (HCCs) compared to transarterial chemoembolization (TACE) and liver transplantation (LT).
METHODS: Among the HCC patients who were managed at Yonsei University Health System between January 2003 and December 2008, 160 patients who met the following criteria were retrospectively enrolled: (1) two or three radiologically diagnosed HCCs; (2) no radiologic vascular invasion; (3) Child-Pugh class A; (4) main tumor smaller than 5 cm in diameter; and (5) platelet count greater than 50 000/mm3. Long-term outcomes were compared among the following three treatment modalities: surgical resection or combined radiofrequency ablation (RFA) (n = 36), TACE (n = 107), and LT (n = 17). The survival curves were computed using the Kaplan-Meier method and compared with a log-rank test. To identify the patients who gained a survival benefit from surgical resection, we also investigated prognostic factors for survival following surgical resection. Multivariate analyses of the prognostic factors for survival were performed using the Cox proportional hazard model.
RESULTS: The overall survival (OS) rate was significantly higher in the surgical resection group than in the TACE group (48.1% vs 28.9% at 5 years, P < 0.005). LT had the best OS rate, which was better than that of the surgical resection group, although the difference was not statistically significant (80.2% vs 48.1% at 5 years, P = 0.447). The disease-free survival rates were also significantly higher in the LT group than in the surgical resection group (88.2% vs 11.2% at 5 years, P < 0.001). Liver cirrhosis was the only significant prognostic factor for poor OS after surgical resection. Clinical liver cirrhosis rates were 55.6% (20/36) in the resection group and 93.5% (100/107) in the TACE group. There were 19 major and 17 minor resections. En bloc resection was performed in 23 patients, multi-site resection was performed in 5 patients, and combined resection with RFA was performed in 8 patients. In the TACE group, only 34 patients (31.8%) were recorded as having complete remission after primary TACE. Seventy-two patients (67.3%) were retreated with repeated TACE combined with other therapies. In patients who underwent surgical resection, the 16 patients who did not have cirrhosis had higher 5-year OS and disease-free survival rates than the 20 patients who had cirrhosis (80.8% vs 25.5% 5-year OS rate, P = 0.006; 22.2% vs 0% 5-year disease-free survival rate, P = 0.048). Surgical resection in the 20 patients who had cirrhosis did not provide any survival benefit when compared with TACE (25.5% vs 24.7% 5-year OS rate, P = 0.225). Twenty-nine of the 36 patients who underwent surgical resection experienced recurrence. Of the patients with cirrhosis, 80% (16/20) were within the Milan criteria at the time of recurrence after resection.
CONCLUSION: Among patients with two or three HCCs, no radiologic vascular invasion, and tumor diameters ≤ 5 cm, surgical resection is recommended only in those without cirrhosis.
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Andreou A, Vauthey JN, Cherqui D, Zimmitti G, Ribero D, Truty MJ, Wei SH, Curley SA, Laurent A, Poon RT, Belghiti J, Nagorney DM, Aloia TA. Improved long-term survival after major resection for hepatocellular carcinoma: a multicenter analysis based on a new definition of major hepatectomy. J Gastrointest Surg 2013; 17:66-77; discussion p.77. [PMID: 22948836 PMCID: PMC3880185 DOI: 10.1007/s11605-012-2005-4] [Citation(s) in RCA: 88] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2012] [Accepted: 08/08/2012] [Indexed: 02/08/2023]
Abstract
BACKGROUND Advances in the surgical management of hepatocellular carcinoma (HCC) have expanded the indications for curative hepatectomy, including more extensive liver resections. The purpose of this study was to examine long-term survival trends for patients treated with major hepatectomy for HCC. PATIENTS AND METHODS Clinicopathologic data for 1,115 patients with HCC who underwent hepatectomy between 1981 and 2008 at five hepatobiliary centers in France, China, and the USA were assessed. In addition to other performance metrics, outcomes were evaluated using resection of ≥4 liver segments as a novel definition of major hepatectomy. RESULTS Major hepatectomy was performed in 539 patients. In the major hepatectomy group, median tumor size was 10 cm (range: 1-27 cm) and 22 % of the patients had bilateral lesions. The TNM Stage distribution included 29 % Stage I, 31 % Stage II, 38 % Stage III, and 2 % Stage IV. The postoperative histologic examination indicated that chronic liver disease was present in 35 % of the patients and tumor microvascular invasion was identified in 60 % of the patients. The 90-day postoperative mortality rate was 4 %. After a median follow-up time of 63 months, the 5-year overall survival rate was 40 %. Patients treated with right hepatectomy (n = 332) and those requiring extended hepatectomy (n = 207) had similar 90-day postoperative mortality rates (4 % and 4 %, respectively, p = 0.976) and 5-year overall survival rates (42 % and 36 %, respectively, p = 0.523). Postoperative mortality and overall survival rates after major hepatectomy were similar among the participating countries (p > 0.1) and improved over time with 5-year survival rates of 30 %, 40 %, and 51 % for the years 1981-1989, 1990-1999, and the most recent era of 2000-2008, respectively (p = 0.004). In multivariate analysis, factors that were significantly associated with worse survivals included AFP level >1,000 ng/mL, tumor size >5 cm, presence of major vascular invasion, presence of extrahepatic metastases, positive surgical margins, and earlier time period in which the major hepatectomy was performed. CONCLUSIONS This multinational, long-term HCC survival analysis indicates that expansion of surgical indications to include major hepatectomy is justified by the significant improvement in outcomes over the past three decades observed in both the East and the West.
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Affiliation(s)
- Andreas Andreou
- Department of Surgical Oncology, The University of Texas MD, Anderson Cancer Center, Houston, TX, USA,
| | - Jean-Nicolas Vauthey
- Department of Surgical Oncology, The University of Texas MD, Anderson Cancer Center, Houston, TX, USA,
| | - Daniel Cherqui
- Department of Digestive and Hepatobiliary Surgery and Liver, Transplantation, Hôpital Henri Mondor, Créteil, France
| | - Giuseppe Zimmitti
- Department of Surgical Oncology, The University of Texas MD, Anderson Cancer Center, Houston, TX, USA,
| | - Dario Ribero
- Department of Surgical Oncology, The University of Texas MD, Anderson Cancer Center, Houston, TX, USA,
| | - Mark J. Truty
- Department of Surgical Oncology, The University of Texas MD, Anderson Cancer Center, Houston, TX, USA,
| | - Steven H. Wei
- Department of Surgical Oncology, The University of Texas MD, Anderson Cancer Center, Houston, TX, USA,
| | - Steven A. Curley
- Department of Surgical Oncology, The University of Texas MD, Anderson Cancer Center, Houston, TX, USA,
| | - Alexis Laurent
- Department of Digestive and Hepatobiliary Surgery and Liver, Transplantation, Hôpital Henri Mondor, Créteil, France
| | - Ronnie T. Poon
- Department of Surgery, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
| | | | - David M. Nagorney
- Department of Gastroenterologic and General Surgery, Mayo Clinic, Rochester, MN, USA
| | - Thomas A. Aloia
- Department of Surgical Oncology, The University of Texas MD, Anderson Cancer Center, Houston, TX, USA,
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Yang J, Yan L, Wang W. Current status of multimodal & combination therapy for hepatocellular carcinoma. Indian J Med Res 2012; 136:391-403. [PMID: 23041732 PMCID: PMC3510885] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/03/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. Surgery offers the only hope for cure. However, the potentially curable method is only possible for a small proportion of those afflicted, for the rest, palliative treatment is indicated. Despite all the treatment options when used as monotherapy, patients with HCC have a poor long term prognosis. In this setting, multimodal and combination therapy has emerged as an alternative treatment modality for HCC. Studies have looked at various forms of combination therapy, including neoadjuvant/adjuvant/downstaging therapy for surgery and the combined modality of non-operative therapies. The novel molecular targeted therapies are also being used as combination regimens for surgery or other non-operative therapies. Some forms of combination therapies, including downstaging therapy for surgery, salvage transplantation, and molecular targeted therapy have been shown to provide survival benefits for well selected patients, and need to be encouraged in the future. And others such as pre-operative bridging therapy for liver transplantation, adjuvant therapy for hepatic resection and combination of local and regional therapies have also shown some benefits in preliminary results, which need confirmation in further studies. In conclusion, multimodal and combination therapy is an encouraging treatment modality for HCC. Future research should continue to unravel the role of combination therapy with properly selected patients and appropriate end points.
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Affiliation(s)
- Jian Yang
- Division of Liver Transplantation, West China Hospital, West China Medical School of Sichuan University, Chengdu, PR China
| | - Lunan Yan
- Division of Liver Transplantation, West China Hospital, West China Medical School of Sichuan University, Chengdu, PR China,Reprint requests: Dr Lunan Yan, Division of Liver Transplantation, West China Hospital, West China School of Medicine, Sichuan University, 37# Guoxue Lane, Chengdu 610041, PR China e-mail:
| | - Wentao Wang
- Division of Liver Transplantation, West China Hospital, West China Medical School of Sichuan University, Chengdu, PR China
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Abstract
OBJECTIVE Patients with hepatocellular carcinoma (HCC) presenting with nonmicronodular or micronodular cirrhosis are usually treated by hepatectomy. The value of resection for patients with hepatitis B virus-related macronodular cirrhosis, however, remains unknown because of potentially fatal complications of this procedure. METHODS Clinicopathological data were analyzed for 85 resected HCC patients with hepatitis B virus-related macronodular cirrhosis. An additional 255 patients with nonmicronodular and micronodular cirrhosis were randomly selected during the same period as the control group. RESULTS Compared with nonmicronodular and micronodular cirrhosis patients, macronodular cirrhotic patients exhibited elevated alanine aminotransferase, aspartate aminotransferase, and γ-glutamyltransferase levels, higher Child-Pugh classification, higher indocyanine green retention rate at 15 min (ICG R15), and more number of total complications. No significant differences were observed between the two groups with regard to major complications, mortality, overall survival, and recurrence-free survival. The morbidity rate was relatively low in patients exhibiting low ICG R15 (<10%). Cox analysis identified small tumors (≤ 5 cm) and radical resection as independent prognostic factors that could predict long-term overall survival. Radical resection can result in high recurrence-free survival in macronodular cirrhotic patients. CONCLUSION Resection is safe for macronodular cirrhotic HCC patients, and radical resection provides a positive outcome. Small-sized patients are good candidates for hepatectomy. Macronodular cirrhosis should not rule out hepatectomy in patients with low ICG R15.
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Cheung TT, Chan SC, Ho CL, Chok KSH, Chan ACY, Sharr WW, Ng KKC, Poon RTP, Lo CM, Fan ST. Can positron emission tomography with the dual tracers [11 C]acetate and [18 F]fludeoxyglucose predict microvascular invasion in hepatocellular carcinoma? Liver Transpl 2011; 17:1218-25. [PMID: 21688383 DOI: 10.1002/lt.22362] [Citation(s) in RCA: 66] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Microvascular invasion is a poor prognostic indicator of the recurrence of hepatocellular carcinoma (HCC) after surgical treatment. Positron emission tomography (PET) with [(18) F]fludeoxyglucose ([(18) F]FDG) as a tracer has been employed to predict the prognosis before surgery for various kinds of tumors, but it has not been found to be sensitive enough for HCC. Thus, [(11) C]acetate has been adopted as an additional tracer. This study was designed to evaluate the ability of dual-tracer PET ([(18) F]FDG and [(11) C]acetate) to predict microvascular invasion before liver resection or transplantation. Fifty-eight HCC patients who were preoperatively examined with whole-body dual-tracer PET were studied. Twenty-five patients were [(18) F]FDG-positive, and 56 were [(11) C]acetate-positive. The sensitivity of [(18) F]FDG in detecting primary HCC was 43%, and the sensitivity of [(11) C]acetate was 93%. Twenty-nine patients had HCC with microvascular invasion according to the final pathological examination. The sensitivity, specificity, positive predictive value, and negative predictive value of [(18) F]FDG PET in predicting microvascular invasion were 55.2%, 69%, 64%, and 60.6%, respectively; the corresponding rates for [(11) C]acetate PET were 93.1%, 0%, 48.2%, and 0%. The factors associated with HCC recurrence, which included multifocal involvement, a large tumor size, microsatellite lesions, poor HCC differentiation, and an advanced stage of disease, were analyzed and compared with positive PET results. A tumor size greater than 5 cm was significantly associated with positive [(18) F]FDG PET results; [(11) C]acetate was not associated with poor prognostic indicators. Preoperative [(18) F]FDG PET may predict microvascular invasion. The addition of [(11) C]acetate improves the overall sensitivity of PET, but it has no incremental value in predicting microvascular invasion.
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Affiliation(s)
- Tan To Cheung
- Department of Surgery, University of Hong Kong, Hong Kong, China.
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Mittler J, McGillicuddy JW, Chavin KD. Laparoscopic liver resection in the treatment of hepatocellular carcinoma. Clin Liver Dis 2011; 15:371-84, vii-x. [PMID: 21689619 DOI: 10.1016/j.cld.2011.03.009] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Laparoscopic liver resection is an emerging technique in liver surgery. Although laparoscopy is well established for several abdominal procedures and is considered by some the preferred approach, laparoscopic hepatic resection has been introduced into clinical practice more widely since 2000. These procedures are performed only in experienced centers and only in a select group of patients. While initially performed only for benign hepatic lesions, the indications for laparoscopic resection have gradually broadened to encompass all kinds of malignant hepatic lesions, including hepatocellular carcinoma in patients with cirrhosis, for whom the advantages of the minimally invasive approach may be most evident.
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Affiliation(s)
- Jens Mittler
- Division of Transplant Surgery, Department of Surgery, Medical University of South Carolina (MUSC), 96 Jonathan Lucas Street Charleston, SC 29425, USA
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25
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Earl TM, Chapman WC. Conventional Surgical Treatment of Hepatocellular Carcinoma. Clin Liver Dis 2011; 15:353-70, vii-x. [PMID: 21689618 DOI: 10.1016/j.cld.2011.03.008] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Liver resection remains the standard therapy for solitary hepatocellular carcinoma in patients with preserved hepatic function. In well-selected patients, 5-year survival rates are good and can approach that of liver transplantation for early-stage disease. Patient selection is critical to optimizing therapeutic benefit, and the health of the native liver must be considered in addition to tumor characteristics. Hepatic recurrence after resection is common. The difficulty lies in deciding which patients with chronic liver disease and small solitary tumors are best served by resection and which should proceed with transplant evaluation; this is the focus of this article.
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Affiliation(s)
- T Mark Earl
- Section of Transplantation, Department of Surgery, Washington University School of Medicine, Washington University, 660 South Euclid Avenue, Campus Box 8109, St Louis, MO 63130, USA
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Giannelli G, Mazzocca A, Fransvea E, Lahn M, Antonaci S. Inhibiting TGF-β signaling in hepatocellular carcinoma. Biochim Biophys Acta Rev Cancer 2011; 1815:214-23. [PMID: 21129443 DOI: 10.1016/j.bbcan.2010.11.004] [Citation(s) in RCA: 52] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2010] [Revised: 11/18/2010] [Accepted: 11/20/2010] [Indexed: 12/17/2022]
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Dosimetric predictor identification for radiation-induced liver disease after hypofractionated conformal radiotherapy for primary liver carcinoma patients with Child-Pugh Grade A cirrhosis. Radiother Oncol 2010; 98:265-9. [PMID: 21056489 DOI: 10.1016/j.radonc.2010.10.014] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2009] [Revised: 10/13/2010] [Accepted: 10/14/2010] [Indexed: 01/12/2023]
Abstract
PURPOSE Radiation-induced liver disease (RILD) is the most severe complication in liver cancer treatment. The aim of this study was to identify dosimetric predictors for RILD in primary liver carcinoma (PLC) patients with Child-Pugh Grade A cirrhosis after hypofractionated conformal radiotherapy (CRT). METHODS AND MATERIALS A total of 114 eligible patients (mean age 45 years old) were enrolled and treated. The mean gross tumor volume (GTV) was (378.3±308.1) cm(3). A median dose of 53 Gy was delivered to the PLC by hypofractionated CRT (three fractions/week) with a median fraction size of 4.6 Gy (range: 4-6 Gy). RESULTS Patients were followed up for 1-79 months (median 19 months) after the completion of irradiation. RILD was diagnosed in nine (7.9%) patients. Univariate analyses revealed that GTV and the percentage of normal liver volume receiving more than 5-40 Gy irradiations (V(5-40)) were related to the risk of developing RILD. Multivariate analyses demonstrated that only GTV and V(20) were independent predictors. Using V(20) as the predictor for RILD, the accuracy, sensitivity, and specificity was 76.3%, 88.9%, and 75.2%, respectively. CONCLUSIONS Our data suggest that V(20) is the unique significant dosimetric predictor for RILD risks in PLC patients with Child-Pugh Grade A cirrhosis after hypofractionated CRT.
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Jarnagin W, Chapman WC, Curley S, D'Angelica M, Rosen C, Dixon E, Nagorney D. Surgical treatment of hepatocellular carcinoma: expert consensus statement. HPB (Oxford) 2010; 12:302-10. [PMID: 20590903 PMCID: PMC2951816 DOI: 10.1111/j.1477-2574.2010.00182.x] [Citation(s) in RCA: 80] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
As the number of effective treatment options has increased, the management of patients with hepatocellular carcinoma has become complex. The most appropriate therapy depends largely on the functional status of the underlying liver. In patients with advanced cirrhosis and tumor extent within the Milan criteria, liver transplantation is clearly the best option, as this therapy treats the cancer along with the underlying hepatic parenchymal disease. As the results of transplantation has become established in patients with limited disease, investigation has increasingly focused on downstaging patients with disease outside of Milan criteria and defining the upper limits of transplantable tumors. In patients with well preserved hepatic function, liver resection is the most appropriate and effective treatment. Hepatic resection is not as constrained by tumor extent and location to the same degree as transplantation and ablative therapies. Some patients who recur after resection may still be eligible for transplantation. Ablative therapies, particularly percutaneous radiofrequency ablation and transarterial chemoembolization have been used primarily to treat patients with low volume irresectable tumors. Whether ablation of small tumors provides long term disease control that is comparable to resection remains unclear.
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Affiliation(s)
- William Jarnagin
- Department of Surgery, Memorial – Sloan Kettering Cancer CenterNew York, NY
| | - William C Chapman
- Section of Transplantation, Barnes – Jewish Hospital, Washington School of MedicineSt. Louis, MO
| | - Steven Curley
- Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer CenterHouston, TX
| | - Michael D'Angelica
- Department of Surgery, Memorial – Sloan Kettering Cancer CenterNew York, NY
| | | | - Elijah Dixon
- Department of Surgery, University of CalgaryCalgary, Canada
| | - David Nagorney
- Department of Gastroenterologic and General Surgery, Mayo ClinicRochester, MN, USA
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29
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Cofer JB, Adams RB. Article Commentary: Fundamentals of Liver Surgery for the Practicing General Surgeon. Am Surg 2010. [DOI: 10.1177/000313481007600511] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Affiliation(s)
- Joseph B. Cofer
- Department of Surgery, University of Tennessee College of Medicine—Chattanooga, Chattanooga, Tennessee
| | - Reid B. Adams
- Department of Surgery, Division of Surgical Oncology, Hepatobiliary and Pancreatic Surgery, University of Virginia Health System, Charlottesville, Virginia
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Jarnagin WR. Management of small hepatocellular carcinoma: a review of transplantation, resection, and ablation. Ann Surg Oncol 2010; 17:1226-33. [PMID: 20405327 DOI: 10.1245/s10434-010-0978-3] [Citation(s) in RCA: 67] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2009] [Indexed: 12/13/2022]
Abstract
PURPOSE AND DESIGN The management of patients with early hepatocellular carcinoma has become increasingly complex. The most appropriate therapy largely depends on the functional status of the underlying liver. Here we review the modalities of transplantation, resection, and ablation in this patient population. RESULTS AND CONCLUSION In patients with cirrhosis and/or portal hypertension, and disease extent within the Milan criteria, liver transplantation is clearly the best option. This modality not only provides therapy for the cancer but also treats the underlying hepatic parenchymal disease. In patients with well-preserved hepatic function, on the other hand, liver resection remains the most appropriate and effective treatment. Hepatic resection is not constrained by the same variables of tumor extent and location that limit the applicability of transplantation and ablative therapies. In addition, patients whose disease recurs after resection are often still eligible for transplantation. Ablative therapies, particularly percutaneous radiofrequency ablation and transarterial embolization/chemoembolization, have been used primarily to treat patients with low-volume unresectable tumors. The question has increasingly been raised regarding whether ablation of small tumors (<3 cm) provides long-term disease control that is comparable to resection. Ablative therapies has also been used as a means of controlling disease in patients who are on transplantation waiting lists, although improved posttransplantation outcome using these techniques has yet to be proven prospectively. The major problem with assessing the efficacy of various treatment modalities in these patients is the heterogeneity of disease presentation, which often precludes the use of certain therapies and therefore makes the conduct of randomized control trial difficult.
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Jarnagin WR. Management of small hepatocellular carcinoma: a review of transplantation, resection, and ablation. Ann Surg Oncol 2010. [PMID: 20405327 DOI: 10.1245/s10434-010-0978-3.] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
PURPOSE AND DESIGN The management of patients with early hepatocellular carcinoma has become increasingly complex. The most appropriate therapy largely depends on the functional status of the underlying liver. Here we review the modalities of transplantation, resection, and ablation in this patient population. RESULTS AND CONCLUSION In patients with cirrhosis and/or portal hypertension, and disease extent within the Milan criteria, liver transplantation is clearly the best option. This modality not only provides therapy for the cancer but also treats the underlying hepatic parenchymal disease. In patients with well-preserved hepatic function, on the other hand, liver resection remains the most appropriate and effective treatment. Hepatic resection is not constrained by the same variables of tumor extent and location that limit the applicability of transplantation and ablative therapies. In addition, patients whose disease recurs after resection are often still eligible for transplantation. Ablative therapies, particularly percutaneous radiofrequency ablation and transarterial embolization/chemoembolization, have been used primarily to treat patients with low-volume unresectable tumors. The question has increasingly been raised regarding whether ablation of small tumors (<3 cm) provides long-term disease control that is comparable to resection. Ablative therapies has also been used as a means of controlling disease in patients who are on transplantation waiting lists, although improved posttransplantation outcome using these techniques has yet to be proven prospectively. The major problem with assessing the efficacy of various treatment modalities in these patients is the heterogeneity of disease presentation, which often precludes the use of certain therapies and therefore makes the conduct of randomized control trial difficult.
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Mannai S, Frikha N, Maghrebi H, Arfa N, Mestiri H, Khalfallah MT, Ammar MSB. The model of end-stage liver disease (MELD) score in predicting postoperative liver failure after hepatic resection of hepatocellular carcinoma in cirrhotic patients: The Tunisian experience. Arab J Gastroenterol 2010. [DOI: 10.1016/j.ajg.2009.12.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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Tsim NC, Frampton AE, Habib NA, Jiao LR. Surgical treatment for liver cancer. World J Gastroenterol 2010; 16:927-33. [PMID: 20180230 PMCID: PMC2828596 DOI: 10.3748/wjg.v16.i8.927] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2009] [Revised: 12/20/2009] [Accepted: 12/27/2009] [Indexed: 02/06/2023] Open
Abstract
Primary liver cancer is amongst the commonest tumors worldwide, particularly in parts of the developing world, and is increasing in incidence. Over the past three decades, surgical hepatic resection has evolved from a high risk, resource intensive procedure with limited application, to a safe and commonly performed operation with a range of indications. This article reviews the approach to surgical resection for malignancies such as hepatocellular cancer, metastatic liver deposits and neuroendocrine tumors. Survival data after resection is also reviewed, as well as indications for curative resection.
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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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Methylated cyclin D2 gene circulating in the blood as a prognosis predictor of hepatocellular carcinoma. Clin Chim Acta 2010; 411:516-20. [PMID: 20064498 DOI: 10.1016/j.cca.2010.01.004] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2009] [Revised: 01/04/2010] [Accepted: 01/04/2010] [Indexed: 01/28/2023]
Abstract
BACKGROUND Prognosis of hepatocellular carcinoma (HCC) remains poor because of high recurrence rate. We examined preoperatively the methylated CCND2 gene levels present in the serum following release from HCC cells as a prognosis predictor in patients undergoing curative hepatectomy. METHODS Quantitative real-time RT-PCR and quantitative methylation-specific PCR were used to measure methylated CCND2 gene and its mRNA levels. RESULTS The CCND2 mRNA levels were down-regulated in HCC with early intrahepatic recurrence (IHR) within 1year of curative hepatectomy. We also identified that this down-regulation was due to promoter hypermethylation. In 70 HCC patients who underwent curative hepatectomy, 39 patients sero-positive for the methylated CCND2 gene (>70pg/ml serum) exhibited a significantly shorter disease-free survival (DFS) period (P=0.02) than the 31 patients who were sero-negative for the methylated CCND2 gene. None of the sero-negative patients demonstrated early IHR, and this method of serum testing did not produce any false-negative predictions for early IHR. Multivariate analysis showed that the serum level of methylated CCND2 was an independent risk factor for DFS (hazard ratio of 1.866, 95% CI: 1.106-3.149). CONCLUSION Methylated CCND2 gene in the serum serves as a prognosis predictor of HCC after curative hepatectomy.
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Shim JH, Kim KM, Lee YJ, Ko GY, Yoon HK, Sung KB, Park KM, Lee SG, Lim YS, Lee HC, Chung YH, Lee YS, Suh DJ. Complete necrosis after transarterial chemoembolization could predict prolonged survival in patients with recurrent intrahepatic hepatocellular carcinoma after curative resection. Ann Surg Oncol 2009; 17:869-77. [PMID: 20033326 DOI: 10.1245/s10434-009-0788-7] [Citation(s) in RCA: 46] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2009] [Indexed: 12/17/2022]
Abstract
BACKGROUND We explored the predictors of response to transarterial chemoembolization (TACE) in patients with recurrent intrahepatic hepatocellular carcinoma (HCC) after hepatectomy and investigated the survival of these patients according to the response to TACE. METHODS We analyzed data from 199 consecutive HCC patients who underwent curative liver resection and who later received repeat TACE for intrahepatic HCC recurrence. RESULTS Of 199 patients, 139 (69.8%) achieved complete necrosis (CN) of HCC after repeated TACE (mean TACE session number, 1.3) and the other 60 (30.2%) (non-CN group) did not achieve CN. At hepatectomy, the CN group showed significantly smaller proportions of tumor capsular invasion, microvascular invasion, and pathologic tumor-node-metastasis stage III or IV HCCs. At first TACE, the CN group showed a significantly greater proportion of patients with time to recurrence > or = 1 year, Child-Pugh class A, serum alpha-fetoprotein (AFP) levels < 200 ng/mL, tumor size < 3 cm, solitary tumors, and nodular tumor types; portal vein invasion were less common than seen in the non-CN group. After multivariate analysis, tumor size < 3 cm and a single tumor at first TACE were independently related to attainment of CN after TACE. Median survival after first TACE was significantly longer in the CN group (48.9 versus 17.0 months). In a Cox regression model, CN after TACE was an independent predictor of favorable survival outcome after first TACE. CONCLUSIONS CN after repeat TACE for postresection intrahepatic recurrence was attained more commonly in patients with smaller tumor size and lower tumor number at first TACE and favored longer survival in recurrent patients.
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Affiliation(s)
- Ju Hyun Shim
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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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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Ishizawa T, Mise Y, Aoki T, Hasegawa K, Beck Y, Sugawara Y, Kokudo N. Surgical technique: new advances for expanding indications and increasing safety in liver resection for HCC: the Eastern perspective. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2009; 17:389-93. [PMID: 19924372 DOI: 10.1007/s00534-009-0231-2] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/01/2009] [Accepted: 09/01/2009] [Indexed: 12/11/2022]
Abstract
PURPOSE We introduce recent advances in surgical techniques and perioperative management in liver resection for hepatocellular carcinoma (HCC). METHODS Our approaches to further enhancing the efficacy of resection for HCC, based on our presentation at "The 6th International Meeting of Hepatocellular Carcinoma: Eastern and Western Experiences" held in Seoul in December 2008, are presented, along with a review of recent advances in this field reported from eastern Asia. RESULTS In our series, liver resection enabled a 5-year overall survival rate of close to 60%, even among patients with multiple HCCs and those with portal hypertension in a background of Child-Pugh class A cirrhosis. Favorable long-term results were obtained by the precise evaluation of liver function using the indocyanine green (ICG) test and the application of perioperative treatments for gastroesophageal varices and severe thrombocytopenia. Furthermore, promising novel techniques have been applied to increase the efficacy of HCC resection, including the preoperative simulation of liver resection, using three-dimensional computed tomography, a "peeling-off" technique for resecting HCC with macroscopic portal venous tumor thrombus, ICG-fluorescent imaging, predeposit autologous plasma transfusion, and laparoscopic liver resection. CONCLUSIONS The safety and accuracy of liver resection for HCC has been continuously enhanced by advances in surgical techniques and perioperative care. Given that the resection of HCC offers a satisfactory overall survival rate for patients with portal hypertension and those with oligonodular multiple tumors, the surgical indications can now be expanded to include such second-best candidates.
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Affiliation(s)
- Takeaki Ishizawa
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
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Cunningham SC, Tsai S, Marques HP, Mira P, Cameron A, Barroso E, Philosophe B, Pawlik TM. Management of early hepatocellular carcinoma in patients with well-compensated cirrhosis. Ann Surg Oncol 2009; 16:1820-1831. [PMID: 19267161 DOI: 10.1245/s10434-009-0364-1] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2008] [Revised: 12/19/2008] [Accepted: 12/20/2008] [Indexed: 01/04/2025]
Abstract
Hepatocellular carcinoma (HCC) usually affects patients with chronic liver disease. While resection is the primary treatment of HCC in patients without cirrhosis, in the setting of moderate to severe cirrhosis, liver transplantation is the preferred therapy, as it simultaneously treats the tumor and the underlying liver condition. The optimal management of patients with HCC and early cirrhosis remains controversial. Although liver transplantation for HCC within the Milan criteria has been shown to have excellent long-term survival rates and low recurrence rates, its application is limited by organ availability. Due to the shortage of donors, a portion of patients drop out from the waiting list due to tumor progression. One alternative to transplantation is hepatic resection. In addition to the reported 50% 5-year survival rates, resection allows a better understanding of tumor biology through pathologic examination of the specimen, which may guide decision-making regarding salvage liver transplantation. Other nonsurgical locoregional therapies, such as transarterial chemoembolization and radiofrequency ablation, also serve as primary therapies and as a bridge to transplantation. The management of patients with early HCC is complex and multidimensional. The care of these patients is best served by a multidisciplinary approach, with consideration of the feasibility of transplantation weighed against the aggressiveness of the tumor biology and underlying hepatic dysfunction. All modalities of therapy should be viewed as complementary, not exclusive, therapeutic strategies.
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Affiliation(s)
- Steven C Cunningham
- Department of Surgery, University of Maryland Medical Center, Baltimore, MD, USA
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Prognostic role of vascular endothelial growth factor in hepatocellular carcinoma: systematic review and meta-analysis. Br J Cancer 2009; 100:1385-92. [PMID: 19401698 PMCID: PMC2694418 DOI: 10.1038/sj.bjc.6605017] [Citation(s) in RCA: 164] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is a highly vascular tumour that expresses vascular endothelial growth factor (VEGF). Various studies have evaluated the prognostic value of VEGF levels in HCC. Its overall test performance remains unclear, however. The aim was to perform a systematic review and meta-analysis of prognostic cohort studies evaluating the use of VEGF as a predictor of survival in patients with treated HCC. Eligible studies were identified through multiple search strategies. Studies were assessed for quality using the Newcastle–Ottawa Tool. Data were collected comparing disease-free and overall survival in patients with high VEGF levels as compared to those with low levels. Studies were pooled and summary hazard ratios were calculated. A total of 16 studies were included for meta-analysis (8 for tissue and 8 for serum). Methodological analysis indicated a trend for higher study quality with serum studies as compared to tissue-based investigations. Four distinct groups were pooled for analysis: tissue overall survival (n=251), tissue disease-free survival (n=413), serum overall survival (n=579), and serum disease-free survival (n=439). High tissue VEGF levels predicted poor overall (HR=2.15, 95% CI: 1.26–3.68) and disease-free (HR=1.69, 95% CI: 1.23–2.33) survival. Similarly, high serum VEGF levels predicted poor overall (HR=2.35, 95% CI: 1.80–3.07) and disease-free (HR=2.36, 95% CI 1.76–3.16) survival. A high degree of inter-study consistency was present in three of four groups analysed. Tissue and serum VEGF levels appear to have significant predictive ability for estimating overall survival in HCC and may be useful for defining prognosis in HCC.
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Abstract
Hepatitis B or C virus infection carries a high risk for genesis of hepatocellular carcinoma (HCC). Most of HCC patients were complicated with cirrhosis. The choice of therapeutic modality is depended on tumor location, metastasis and liver function. The only proven potentially curative therapy for HCC are hepatic resection or liver transplantation in highly selected patients. For the patients with non-resectable HCC, chemoembolization and ablation therapy may be used as the primary therapy. Agents for highly advanced HCC should be given based on clinical trials.
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Abstract
The indications and the results for liver resection for hepatocellular cancer (HCC) depend on the stage of the tumor at diagnosis, the functional reserve of the liver, and the use of suitably adapted surgical techniques. This article briefly discusses liver resection for HCC in patients who do not have chronic liver disease and then discusses liver resection for HCC in patients who have chronic liver disease.
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Ishizawa T, Hasegawa K, Aoki T, Takahashi M, Inoue Y, Sano K, Imamura H, Sugawara Y, Kokudo N, Makuuchi M. Neither multiple tumors nor portal hypertension are surgical contraindications for hepatocellular carcinoma. Gastroenterology 2008; 134:1908-16. [PMID: 18549877 DOI: 10.1053/j.gastro.2008.02.091] [Citation(s) in RCA: 568] [Impact Index Per Article: 33.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2007] [Revised: 01/23/2008] [Accepted: 02/28/2008] [Indexed: 12/02/2022]
Abstract
BACKGROUND & AIMS The surgical indications for multiple hepatocellular carcinomas (HCCs) and for HCC with portal hypertension (PHT) remain controversial. METHODS We reviewed 434 patients who had undergone an initial resection for HCC and divided them into a multiple (n = 126) or single (n = 308) group according to the number of tumors. We also classified 386 of the patients into a PHT group (n = 136) and a no-PHT (n = 250) group according to whether they had PHT (defined by the presence of esophageal varices or a platelet count of <100,000/microL in association with splenomegaly). RESULTS Among Child-Pugh class A patients, the overall survival rates in the multiple group were 58% at 5 years, and 56% in the PHT group, which were lower than those in the single group (68%, P = .035) and the no-PHT group (71%, P = .008). Among Child-Pugh class B patients with multiple HCCs, the 5-year overall survival rate was 19%. Multivariate analyses revealed that the presence of multiple tumors was an independent risk factor for postoperative recurrence (relative risk, 1.64; 95% confidence interval, 1.23-2.18; P = .001). A second resection resulted in satisfactory overall survival after the diagnosis of recurrence in the multiple (73% at 3 years) or PHT (73%) groups, as well as in the single (79%) or no PHT (81%) groups. CONCLUSIONS Resection can provide survival benefits even for patients with multiple tumors in a background of Child-Pugh class A cirrhosis, as well as in those with PHT.
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Affiliation(s)
- Takeaki Ishizawa
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
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Chemoembolization of hepatocellular carcinoma: patient status at presentation and outcome over 15 years at a single center. AJR Am J Roentgenol 2008; 190:608-15. [PMID: 18287429 DOI: 10.2214/ajr.07.2879] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
OBJECTIVE We report the outcome of the care of 209 patients with hepatocellular carcinoma with a focus on relevant scoring systems for predicting overall survival and time to progression and on changes in presentation status and outcome from 1991 to 2006. MATERIALS AND METHODS Hepatic arterial chemoembolization was performed on 209 patients in 375 sessions. Disease status was evaluated with the Child-Pugh, Okuda, Cancer of the Liver Italian Program, and American Joint Committee on Cancer (AJCC) systems. Changes in status at presentation from 1991 to 2006 and change in overall survival period and time to progression were analyzed. RESULTS Median and mean overall survival periods for the entire group were 376 and 574 +/- 61 days. Median and mean times to progression were 267 and 409 +/- 54 days. Forty-nine patients underwent liver transplantation a median of 143 days after chemoembolization. The median and mean overall survival times among patients not undergoing transplantations were 466 and 574 +/- 61 days. Okuda score (p < 0.0001) and AJCC stage (p = 0.014) were the best predictors of overall survival and time to progression, respectively. Patients with disease with an Okuda I score and in AJCC stage I or II had median and mean overall survival periods of 667 and 992 +/- 176 days and times to progression of 378 and 589 +/- 110 days. Clinical status at presentation, overall survival period (p = 0.64), and time to progression (p = 0.44) were unchanged from 1991 to 2006. The 30-day mortality was 3.2%. CONCLUSION Patients treated with hepatic arterial chemoembolization for HCC in Okuda score I and AJCC stage I or II have more durable survival than previously reported in a U.S. population.
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Radiation dose limits and liver toxicities resulting from multiple yttrium-90 radioembolization treatments for hepatocellular carcinoma. J Vasc Interv Radiol 2008; 18:1375-82. [PMID: 18003987 DOI: 10.1016/j.jvir.2007.07.016] [Citation(s) in RCA: 92] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
PURPOSE To assess the relationship between cumulative hepatic lobar radiation dose and liver toxicities in patients with hepatocellular carcinoma (HCC) treated with multiple sessions of yttrium-90 radioembolization. MATERIALS AND METHODS Forty-one patients with HCC (age range, 46-82 years) underwent radioembolization with 90Y. Patients were classified according to the Okuda scoring system. All patients received single liver lobar treatments on two or more occasions according to standard clinical 90Y embolization protocol. Cumulative radiation dose to each liver lobe was measured and patients were followed to assess liver toxicities. Statistical analysis was performed with the Student t test and Kaplan-Meier analysis. RESULTS Patients with Okuda stage I disease received more treatments than those with Okuda stage II disease (mean, 2.65 vs 2.24; P<.05). For average cumulative radiation dose, patients with Okuda stage I disease received 247 Gy (range, 88-482 Gy) and those with Okuda stage II disease received 198 Gy (range, 51-361 Gy; P<.05). A total of 13 toxicities occurred in seven patients (16%). Patients with Okuda stage I disease were given a greater cumulative dose than patients with Okuda stage II disease before worsening of liver function: 390 Gy versus 196 Gy (P<.005). For patients with Okuda stage I disease, a higher cumulative radiation dose was associated with occurrence of one or more toxicities: 222 Gy (no toxicities) versus 390 Gy (>or=1 toxicity; P<.005). No correlation between cumulative radiation dose and liver toxicities existed in patients with Okuda stage II disease. The maximum tolerated dose was between 222 and 390 Gy. Median survival times were 660 and 431 days for patients with Okuda stage I and stage II disease, respectively. CONCLUSIONS Patients with HCC can tolerate high cumulative radiation doses with 90Y therapy. Compared with patients with Okuda stage II disease, patients with Okuda stage I disease tolerate a higher cumulative radiation dose without liver toxicity, but liver toxicities increase with increasing cumulative radiation doses.
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Yan K, Chen MH, Yang W, Wang YB, Gao W, Hao CY, Xing BC, Huang XF. Radiofrequency ablation of hepatocellular carcinoma: long-term outcome and prognostic factors. Eur J Radiol 2007; 67:336-347. [PMID: 17765421 DOI: 10.1016/j.ejrad.2007.07.007] [Citation(s) in RCA: 90] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2007] [Revised: 06/16/2007] [Accepted: 07/19/2007] [Indexed: 12/14/2022]
Abstract
PURPOSE To investigate the efficacy of radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC), and the prognostic factors for post-RFA survival rate. METHODS From 1999 to 2006, 266 patients with 392 HCCs underwent ultrasound guided RFA treatment. They were 216 males and 50 females, average age 59.4+/-15.4 years (24-87 years). The HCC were 1.2-6.7 cm in diameters (average 3.9+1.3 cm). There were 158 patients with single tumor, and the rest had multiple (2-5) tumors. Univariate and multivariate analysis with 19 potential variables were examined to identify prognostic factors for post-RFA survival rate. RESULTS The overall post-RFA survival rates at 1st, 3rd, and 5th year were 82.9%, 57.9% and 42.9%, respectively. In the 60 patients with stage I HCC (AJCC staging), the 1-, 3-, 5-year survival rate were 94.8%, 76.4% and 71.6%, significantly higher than the 148 patients with stage II-IV tumors (81.8%, 57.6% and 41.2%, P=0.006). For the 58 patients with post-surgery recurrent HCC, the survival rates were 73.2%, 41.9% and 38.2% at the 1st, 3rd, and 5th year, which were significantly lower than those of stage I HCC (P=0.005). Nine potential factors were found with significant effects on survival rate, and they were number of tumors, location of tumors, pre-RFA liver function enzymes, Child-Pugh classification, AJCC staging, primary or recurrent HCC, tumor pathological grading, using mathematical protocol in RFA procedure and tumor necrosis 1 month after RFA. After multivariate analysis, three factors were identified as independent prognostic factors for survival rate, and they were Child-Pugh classification, AJCC staging and using mathematical protocol. CONCLUSION Identifying prognostic factors provides important information for HCC patient management before, during and after RFA. This long-term follow-up study on a large group of HCC patients confirmed that RFA could not only achieve favorable outcome on stage I HCC, but also be an effective therapy for stage II-IV or recurrent HCC.
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Affiliation(s)
- Kun Yan
- Department of Ultrasound, Peking University School of Oncology, Beijing Cancer Hospital & Institute, No. 52 Fu-cheng Road, Hai-dian District, Beijing 100036, China
| | - Min Hua Chen
- Department of Ultrasound, Peking University School of Oncology, Beijing Cancer Hospital & Institute, No. 52 Fu-cheng Road, Hai-dian District, Beijing 100036, China.
| | - Wei Yang
- Department of Ultrasound, Peking University School of Oncology, Beijing Cancer Hospital & Institute, No. 52 Fu-cheng Road, Hai-dian District, Beijing 100036, China
| | - Yan Bin Wang
- Department of Ultrasound, Peking University School of Oncology, Beijing Cancer Hospital & Institute, No. 52 Fu-cheng Road, Hai-dian District, Beijing 100036, China
| | - Wen Gao
- Department of Ultrasound, Peking University School of Oncology, Beijing Cancer Hospital & Institute, No. 52 Fu-cheng Road, Hai-dian District, Beijing 100036, China
| | - Chun Yi Hao
- Department of Ultrasound, Peking University School of Oncology, Beijing Cancer Hospital & Institute, No. 52 Fu-cheng Road, Hai-dian District, Beijing 100036, China
| | - Bao Cai Xing
- Department of Surgery, Peking University School of Oncology, Beijing Cancer Hospital & Institute, No. 52 Fu-cheng Road, Hai-dian District, Beijing 100036, China
| | - Xin Fu Huang
- Department of Surgery, Peking University School of Oncology, Beijing Cancer Hospital & Institute, No. 52 Fu-cheng Road, Hai-dian District, Beijing 100036, China
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Capussotti L, Ferrero A, Viganò L, Polastri R, Tabone M. Liver resection for HCC with cirrhosis: surgical perspectives out of EASL/AASLD guidelines. Eur J Surg Oncol 2007; 35:11-5. [PMID: 17689043 DOI: 10.1016/j.ejso.2007.06.005] [Citation(s) in RCA: 45] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2007] [Accepted: 06/20/2007] [Indexed: 02/06/2023] Open
Abstract
EASL/AASLD guidelines clearly define indications for liver surgery for HCC: patients with single HCC and completely preserved liver function without portal hypertension. These guidelines exclude from operation many patients that could benefit from radical resection and that are daily scheduled for hepatectomy in surgical centers. Patients with large tumors or with portal vein thrombosis cannot be transplanted or treated by interstitial treatments. In selected cases liver resection may obtain good long-term outcomes, significantly better than non-curative therapies. In cases of multinodular HCC, liver transplantation is the treatment of choice within Milan criteria; patients beyond these limits can benefit from liver resection, especially if only two nodules are diagnosed: even if they have a worse prognosis, survival results after liver surgery are better than those reported after TACE or conservative treatments. EASL/AASLD guidelines excluded from operating patients with portal hypertension but data about this topic are not conclusive and further studies are necessary. Selected patients with mild portal hypertension could probably be scheduled for liver resection and, considering the shortage of donors, listing for transplantation could be avoided. In conclusion, guidelines for HCC treatment should consider good results of liver resection for advanced HCC, and indications for hepatectomy should be expanded in order not to exclude from radical therapy patients that could benefit from it.
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Affiliation(s)
- L Capussotti
- Department of Surgery, Ospedale Mauriziano Umberto I, Largo Turati 62, Torino, Italy.
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Williams R, White J, Croce M, Dilawari R. Surgical Options in the Treatment of Hepatocellular Carcinoma. Am Surg 2007. [DOI: 10.1177/000313480707300704] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
In response to an increase in hepatitis C virus infection in the United States, we reviewed our experience with surgically treated hepatocellular carcinoma in an academic setting to assess the proper treatment protocol for patients who are amenable to surgical therapy. A chart review was conducted on all patients with a diagnosis of hepatocellular carcinoma and surgical therapy from 1990 to 2006 identified through the tumor registries at three university-affiliated institutions. Data on patient characteristics, tumor features, and complications were collected. Outcomes evaluated included recurrence and survival. One hundred three patients were identified; 44 underwent resection, 49 underwent transplantation, and 11 underwent radiofrequency ablation. Patients undergoing transplantation had more severe liver disease and less advanced tumors. Recurrence was lower in the transplant group. Survival in the resection group was 65 per cent, 28 per cent, and 24 per cent at 1, 3, and 5 years. Survival in the transplanted group was 83 per cent, 65 per cent, and 52 per cent at 1, 3, and 5 years. Transplantation offers better survival than resection for patients with hepatocellular carcinoma. Patients with stage I disease may be eligible for resection based on small tumor size and liver function; however, these patients should be considered for transplantation to improve their long-term survival.
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Affiliation(s)
- Regan Williams
- Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee
| | - Jared White
- Department of Surgery, University of Alabama, Birmingham, Alabama
| | - Martin Croce
- Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee
| | - Raza Dilawari
- Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee
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Ho MC, Lin JJ, Chen CN, Chen CC, Lee H, Yang CY, Ni YH, Chang KJ, Hsu HC, Hsieh FJ, Lee PH. A gene expression profile for vascular invasion can predict the recurrence after resection of hepatocellular carcinoma: a microarray approach. Ann Surg Oncol 2007; 13:1474-84. [PMID: 17009164 DOI: 10.1245/s10434-006-9057-1] [Citation(s) in RCA: 51] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND Recurrence after hepatocellular carcinoma (HCC) resection is the major obstacle to improved survival. The presence of vascular invasion (VI) in pathology specimens is a well-known unfavorable prognostic factor for HCC recurrence. Though some VI-related genes have been reported, their association with recurrence-free survival is not known. We hypothesized that a gene expression profile for VI can predict the recurrence of HCC after liver resection. METHODS Eighteen patients receiving complete HCC resection were included as a "training group". Genome-wide gene expression profile was obtained for each tumor using a microarray technique. Datasets were subjected to clustering analysis supervised by the presence or absence of VI to obtain 14 discriminative genes. We then applied those genes to execute pattern recognition using the k-Nearest Neighbor (KNN) classification method, and the best model for this VI gene signature to predict recurrence-free survival in the training group was obtained. The resulting model was then tested in an independent "test group" of 35 patients. RESULTS A 14-gene profile was extracted which could accurately separate ten patients with VI and eight patients without VI in the "training group". In the "test group", significant difference in disease-free survival was found between patients predicted to have and not to have recurrence (P = .02823). In patients with stage_I disease, this model can also predict outcomes (P = .000205). CONCLUSIONS Using the 14-gene expression profile extracted from microarrays based on the presence of VI can effectively predict recurrence after HCC resection. This approach might facilitate "personalized medicine" for HCC patients after surgical resection.
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Affiliation(s)
- Ming-Chih Ho
- Department of Surgery, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, 100, Taiwan
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Shah SA, Cleary SP, Wei AC, Yang I, Taylor BR, Hemming AW, Langer B, Grant DR, Greig PD, Gallinger S. Recurrence after liver resection for hepatocellular carcinoma: risk factors, treatment, and outcomes. Surgery 2006; 141:330-9. [PMID: 17349844 DOI: 10.1016/j.surg.2006.06.028] [Citation(s) in RCA: 323] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2006] [Revised: 05/17/2006] [Accepted: 06/24/2006] [Indexed: 02/06/2023]
Abstract
BACKGROUND Tumor recurrence remains the major cause of death after curative resection for hepatocellular carcinoma (HCC). The purpose of this study was to identify risk factors for the recurrence of HCC and to examine long-term outcomes after resection. METHODS From July 1992 to July 2004, 193 consecutive patients who underwent hepatic resection as primary therapy with curative intent for HCC were included in this single-center analysis. The perioperative mortality rate was 5%. Time to recurrence (disease-free survival) and overall survival were determined by Kaplan-Meier analysis. Demographic, tumor, and treatment characteristics were tested for their prognostic significance by univariate and multivariate analysis with the log-rank test and the Cox proportional hazards model, respectively. RESULTS Median overall survival for the entire cohort was 71 +/- 11 months; disease-free survival was 34 months (range, 1-149 months). After a median follow-up time of 34 months, 98 patients (51%) experienced recurrent cancer; initial tumor recurrence was confined to the liver in 86 patients (88%). With the use of multivariate analysis, preoperative vascular invasion detected on radiologic imaging studies; postoperative vascular invasion found on pathologic assessment, and intermediate and poor tumor differentiation and tumor size and number were significant predictors of disease-free survival. Of the 98 patients who had tumor recurrence, 53 patients (54%) underwent additional therapy (ablation, 31 patients; re-resection, 11 patients; transarterial chemoembolization, 8 patients; liver transplantation, 3 patients) with improvement in survival. CONCLUSION Despite recurrences in >50% of patients, long-term survival can be achieved after resection of HCC. Identification of risk factors, close follow-up evaluation, and early detection are mandatory because recurrences that are confined to the liver may be amenable to treatment with an additional survival benefit.
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Affiliation(s)
- Shimul A Shah
- Department of Surgery, Toronto General Hospital, University of Toronto, Toronto, Canada.
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