|
1
|
Shabangu CS, Su WH, Li CY, Yu ML, Dai CY, Huang JF, Chuang WL, Wang SC. Systematic integration of molecular and clinical approaches in HCV-induced hepatocellular carcinoma. J Transl Med 2024; 22:268. [PMID: 38475805 PMCID: PMC10935926 DOI: 10.1186/s12967-024-04925-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Accepted: 01/23/2024] [Indexed: 03/14/2024] Open
Abstract
BACKGROUND MicroRNAs (miRNAs) play a crucial role in gene expression and regulation, with dysregulation of miRNA function linked to various diseases, including hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). There is still a gap in understanding the regulatory relationship between miRNAs and mRNAs in HCV-HCC. This study aimed to investigate the function and effects of persistent HCV-induced miRNA expression on gene regulation in HCC. METHODS MiRNA array data were used to identify differentially expressed miRNAs and their targets, and miRNAs were analyzed via DIANA for KEGG pathways, gene ontology (GO) functional enrichment, and Ingenuity Pathways Analysis (IPA) for hepatotoxicity, canonical pathways, associated network functions, and interactive networks. RESULTS Seventeen miRNAs in L-HCV and 9 miRNAs in S-HCV were differentially expressed, and 5 miRNAs in L-HCV and 5 miRNAs in S-HCV were significantly expressed in liver hepatocellular carcinoma (LIHC) tumors. Grouped miRNA survival analysis showed that L-HCV miRNAs were associated with survival in LIHC, and miRNA‒mRNA targets regulated viral carcinogenesis and cell cycle alteration through cancer pathways in LIHC. MiRNA-regulated RCN1 was suppressed through miRNA-oncogene interactions, and suppression of RCN1 inhibited invasion and migration in HCC. CONCLUSION Persistent HCV infection induced the expression of miRNAs that act as tumor suppressors by inhibiting oncogenes in HCC. RCN1 was suppressed while miRNAs were upregulated, demonstrating an inverse relationship. Therefore, hsa-miR-215-5p, hsa-miR-10b-5p, hsa-let-7a-5p and their target RCN1 may be ideal biomarkers for monitoring HCV-HCC progression.
Collapse
Affiliation(s)
- Ciniso Sylvester Shabangu
- Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan
| | - Wen-Hsiu Su
- Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan
- Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-Sen University, Kaohsiung, Taiwan
| | - Chia-Yang Li
- Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lung Yu
- Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-Sen University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan
- Hepatitis Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan
| | - Chia-Yen Dai
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan
- Hepatitis Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan
| | - Jee-Fu Huang
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan
- Hepatitis Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan
| | - Wan-Long Chuang
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan
- Hepatitis Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan
| | - Shu-Chi Wang
- Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan.
- Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan.
- Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-Sen University, Kaohsiung, Taiwan.
- Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
| |
Collapse
|
|
2
|
Berger JM, Alany A, Berchtold L, Puhr R, Friedrich A, Scheiner B, Prager GW, Preusser M, Berghoff AS, Bergen ES. Prognosticators of survival in patients with metastatic pancreatic cancer and ascites. ESMO Open 2023; 8:102048. [PMID: 37977000 PMCID: PMC10774951 DOI: 10.1016/j.esmoop.2023.102048] [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: 08/02/2023] [Revised: 09/27/2023] [Accepted: 09/28/2023] [Indexed: 11/19/2023] Open
Abstract
BACKGROUND Identification of factors associated with survival after ascites diagnosis in metastatic pancreatic cancer (mPC) patients may guide treatment decisions and help to maintain quality of life in this highly symptomatic patient collective. PATIENTS AND METHODS All patients treated for mPC at the Medical University of Vienna between 2010 and 2019 developing ascites throughout their course of disease were identified by retrospective chart review. General risk factors, metastatic sites, systemic inflammation and liver function parameters, as well as type of treatment after ascites diagnosis were investigated for associations with survival. RESULTS One hundred and seventeen mPC patients with ascites were included in this study. Median time from mPC to ascites diagnosis was 8.9 months (range 0-99 months) and median overall survival (OS) after ascites diagnosis was 27.4 days (range 21.3-42.6 days). Identified prognostic factors at ascites diagnosis independently associated with an impaired OS were presence of liver metastases [hazard ratio (HR): 2.07, 95% confidence interval (CI) 1.13-3.79, P = 0.018), peritoneal carcinomatosis (HR: 1.74, 95% CI 1.11-2.71, P = 0.015), and portal vein obstruction (HR: 2.52, 95% CI 1.29-4.90, P = 0.007). Compared with best supportive care, continuation of systemic therapy after ascites diagnosis was independently associated with survival (HR: 0.35, 95% CI 0.20-0.61, P < 0.001) with a median OS of 62 days (95% CI 51-129 days, P < 0.001) versus 16 days (95% CI 11-24 days), respectively. CONCLUSIONS Liver and peritoneal metastases as well as portal vein obstruction were found to be prognostic factors after ascites diagnosis in mPC patients. Continuation of systemic therapy after ascites diagnosis was associated with a longer OS, which needs to be evaluated in larger clinical trials including quality-of-life assessment.
Collapse
Affiliation(s)
- J M Berger
- Division of Oncology, Department of Medicine I, Medical University of Vienna, Vienna; Christian Doppler Laboratory for Personalized Immunotherapy, Department of Medicine I, Medical University of Vienna, Vienna
| | - A Alany
- Division of Oncology, Department of Medicine I, Medical University of Vienna, Vienna
| | - L Berchtold
- Division of Oncology, Department of Medicine I, Medical University of Vienna, Vienna
| | - R Puhr
- Division of Oncology, Department of Medicine I, Medical University of Vienna, Vienna
| | - A Friedrich
- Division of Oncology, Department of Medicine I, Medical University of Vienna, Vienna
| | - B Scheiner
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - G W Prager
- Division of Oncology, Department of Medicine I, Medical University of Vienna, Vienna
| | - M Preusser
- Division of Oncology, Department of Medicine I, Medical University of Vienna, Vienna; Christian Doppler Laboratory for Personalized Immunotherapy, Department of Medicine I, Medical University of Vienna, Vienna
| | - A S Berghoff
- Division of Oncology, Department of Medicine I, Medical University of Vienna, Vienna; Christian Doppler Laboratory for Personalized Immunotherapy, Department of Medicine I, Medical University of Vienna, Vienna
| | - E S Bergen
- Division of Oncology, Department of Medicine I, Medical University of Vienna, Vienna.
| |
Collapse
|
|
3
|
Chang PY, Lee RC, Liang PC, Liu YS, Chuang VP, Wu DK, Cheng YF, Huang JI, Tseng HS, Hung CF, Wu RH, Chern MC, Cheng HM, Wu CH, Cheng SM, Chiang CL, Liang HL. Multidisciplinary Taiwan consensus for the use of conventional TACE in hepatocellular carcinoma treatment. Front Oncol 2023; 13:1186674. [PMID: 37427137 PMCID: PMC10328116 DOI: 10.3389/fonc.2023.1186674] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Accepted: 06/05/2023] [Indexed: 07/11/2023] Open
Abstract
Developed in early 1980s, transarterial chemoembolization (TACE) with Lipiodol was adopted globally after large-scale randomized control trials and meta-analyses proving its effectiveness were completed. Also known as "conventional TACE" (cTACE), TACE is currently the first-line treatment for patients with unresectable intermediate stage hepatocellular carcinoma (HCC) and delivers both ischemic and cytotoxic effects to targeted tumors. Although new technology and clinical studies have contributed to a more comprehensive understanding of when and how to apply this widely-adopted therapeutic modality, some of these new findings and techniques have yet to be incorporated into a guideline appropriate for Taiwan. In addition, differences in the underlying liver pathologies and treatment practices for transcatheter embolization between Taiwan and other Asian or Western populations have not been adequately addressed, with significant variations in the cTACE protocols adopted in different parts of the world. These mainly revolve around the amount and type of chemotherapeutic agents used, the type of embolic materials, reliance on Lipiodol, and the degree of selectiveness in catheter positioning. Subsequently, interpreting and comparing results obtained from different centers in a systematic fashion remain difficult, even for experienced practitioners. To address these concerns, we convened a panel of experts specializing in different aspects of HCC treatment to devise modernized recommendations that reflect recent clinical experiences, as well as cTACE protocols which are tailored for use in Taiwan. The conclusions of this expert panel are described herein.
Collapse
Affiliation(s)
- Pi-Yi Chang
- Department of Radiology, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Rheun-Chuan Lee
- Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Po-Chin Liang
- Department of Radiology, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan
| | - Yi-Sheng Liu
- Department of Medical Imagine, National Cheng Kung University Hospital, Tainan, Taiwan
| | - Vicent P. Chuang
- Department of Radiology, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan
| | - Ding-Kwo Wu
- Department of Radiology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Yu-Fan Cheng
- Department of Radiology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Jen-I. Huang
- Department of Radiology, Tungs’ Taichung Metroharbor Hospital, Taichung, Taiwan
| | - Hsiuo-Shan Tseng
- Department of Radiology, Cheng Hsin General Hospital, Taipei, Taiwan
| | - Chien-Fu Hung
- Department of Radiology, Chang−Gung Memorial Hospital, Taoyuan, Taiwan
| | - Reng-Hong Wu
- Department of Radiology, Chi Mei Medical Center, Tainan, Taiwan
| | - Ming-Chih Chern
- Department of Radiology, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan
| | - Hua-Ming Cheng
- Department of Radiology, Chi Mei Medical Center, Tainan, Taiwan
| | - Chih-Horng Wu
- Department of Radiology, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan
| | - She-Meng Cheng
- Department of Radiology, MacKay Memorial Hospital, Taipei, Taiwan
| | - Chia-Ling Chiang
- Department of Radiology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Huei-Lung Liang
- Department of Radiology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| |
Collapse
|
|
4
|
Sakamoto K, Ogawa K, Tamura K, Honjo M, Funamizu N, Takada Y. Prognostic Role of the Intrahepatic Lymphatic System in Liver Cancer. Cancers (Basel) 2023; 15:2142. [PMID: 37046803 PMCID: PMC10093457 DOI: 10.3390/cancers15072142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2023] [Revised: 03/30/2023] [Accepted: 04/03/2023] [Indexed: 04/08/2023] Open
Abstract
Although several prognosticators, such as lymph node metastasis (LNM), were reported for hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), the prognostic impact of intrahepatic lymphatic vessel invasion (LVI) in liver cancer has rarely been reported. We sought to clarify the prognostic impact of intrahepatic lymphatic system involvement in liver cancer. We systematically reviewed retrospective studies that described LVI and clinical outcomes of liver cancer and also included studies that investigated tumor-associated lymphangiogenesis. We conducted a meta-analysis using RevMan software (version 5.4.1; Cochrane Collaboration, Oxford, UK). The prognostic impact of intrahepatic LVI in HCC was not reported previously. However, tumor-associated lymphangiogenesis reportedly correlates with prognosis after HCC resection. The prognostic impact of intrahepatic LVI was reported severally for ICC and a meta-analysis showed that overall survival was poorer in patients with positive LVI than with negative LVI after resection of ICC. Lymphangiogenesis was also reported to predict unfavorable prognosis in ICC. Regarding colorectal liver metastases, LVI was identified as a poor prognosticator in a meta-analysis. A few reports showed correlations between LVI/lymphangiogenesis and LNM in liver cancer. LVI and lymphangiogenesis showed worse prognostic impacts for liver cancer than their absence, but further study is needed.
Collapse
Affiliation(s)
- Katsunori Sakamoto
- Department of Hepato-Biliary-Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine, 454 Kou, Shitsukawa, Toon 791-0295, Ehime, Japan
| | | | | | | | | | | |
Collapse
|
|
5
|
Hussein MA, Radwan AFM, Fawzi MM, Rashed LA, Saad EHAI. MicroRNA 21as a novel biomarker in hepatitis C virus-related hepatocellular carcinoma. THE EGYPTIAN JOURNAL OF INTERNAL MEDICINE 2022. [DOI: 10.1186/s43162-022-00136-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Hepatocellular carcinoma is considered one of the most common cancers occurring in human population all over the world. It became an increasingly threatening malignancy due to both morbidity and mortality. Chronic viral hepatitis B and hepatitis C are two risk factors, which account for 80–90% of all HCC cases worldwide. Alfa Feto protien is used as a tumor marker for HCC diagnosis and prognosis prediction; however, its false negative rate when used alone is as high as 40% for patients with early-stage HCC. AFP levels remain normal in 15–30% of all the patients, even patients with advanced HCC. It has been demonstrated that miRNAs (MicroRNAs) are an important class of non-coding RNAs. They act as tumor oncogenes or suppressors and are involved in the HCC development. MiRNAs are endogenous nucleotides that can be found in intra- and extracellular spaces, such as the blood, urine, and saliva.
The study evaluated the miRNA 21 as a novel biomarker in patients with HCV related hepatocellular carcinoma.
Results
The study was conducted on three groups. Group (1) included 25 patients with liver cirrhosis due to hepatitis C virus infection. Group (2) included 25 patients with hepatocellular carcinoma (HCC) on top of liver cirrhosis due to hepatitis C virus infection. Group (3) included 10 normal control subjects. There was a significant difference in the mean level of miRNA between the three groups with p value < 0.001 with the highest value in group 2 ( 8.28 ± 2.55), then in group1 (5.04 ± 2.11) and the lowest in group 3 (control) (1.02 ± 0.07). MiRNA 21 has a sensitivity of 68% and a specificity of 96%, to differentiate between the liver cirrhosis group and HCC group.
Conclusion
miRNA 21 can be a promising marker for detection of patients with HCV-related hepatocellular carcinoma, with higher specificity compared to α feto protein; however, its cost is higher.
Collapse
|
|
6
|
Comparisons of Viral Etiology and Outcomes of Hepatocellular Carcinoma Undergoing Liver Resection between Taiwan and Vietnam. Viruses 2022; 14:v14112571. [PMID: 36423180 PMCID: PMC9695296 DOI: 10.3390/v14112571] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Revised: 11/17/2022] [Accepted: 11/19/2022] [Indexed: 11/22/2022] Open
Abstract
Epidemiologic data have suggested that etiologic variations of hepatocellular carcinoma (HCC) exist in different geographic areas, and might be associated with different outcomes. We compared the viral etiology, clinicopathological characteristics and surgical outcomes between 706 Taiwanese and 1704 Vietnamese patients with HCC undergoing liver resection. Vietnamese patients had a significantly higher ratio of hepatitis B virus (HBV) (p < 0.001) and a lower ratio of hepatitis C virus (HCV) (p < 0.001) and non-B non-C than Taiwanese patients. Among patients with HBV or non-B non-C, the mean age was younger in Vietnam than in Taiwan (p < 0.001, p = 0.001, respectively). The HCC patients in Vietnam had significantly higher serum alpha-fetoprotein (AFP) levels (p < 0.001), larger tumors (p < 0.001), and a higher ratio of macrovascular invasion (p < 0.001) and extrahepatic metastasis (p < 0.001), compared to those in Taiwan. Patients treated in Vietnam had a higher tumor recurrent rate (p < 0.001), but no difference in overall survival was found between both groups. In subgroup analysis, the recurrent rate of HCC was the highest in patients with dual HBV/HCV, followed by HCV or HBV, and non-B non-C (p < 0.001). In conclusion, although the viral etiology and clinicopathological characteristics of HCC differed, postoperative overall survival was comparable between patients in Taiwan and Vietnam.
Collapse
|
|
7
|
Izzo F, Mason MC, Silberfein EJ, Massarweh NN, Hsu C, Tran Cao HS, Palaia R, Piccirillo M, Belli A, Patrone R, Fusco R, Granata V, Curley SA. Long-Term Survival and Curative-Intent Treatment in Hepatitis B or C Virus-Associated Hepatocellular Carcinoma Patients Diagnosed during Screening. BIOLOGY 2022; 11:biology11111597. [PMID: 36358298 PMCID: PMC9687526 DOI: 10.3390/biology11111597] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Revised: 10/24/2022] [Accepted: 10/31/2022] [Indexed: 11/06/2022]
Abstract
Background: We initiated a prospective screening trial in patients with hepatitis to diagnose HCC in the early stage and to evaluate the impact on long-term survival. Methods: From 1993−2006, 10,372 patients with chronic hepatitis B (14%), hepatitis C (81%), or both (5%) were enrolled in an HCC screening program. All patients underwent liver biopsy at enrollment. Transabdominal ultrasonography and serum alpha-fetoprotein were evaluated every 6 months. Abnormal screening results led to axial imaging and tumor biopsy. Results: Cirrhosis was confirmed on biopsy in 2074 patients (20%). HCC was diagnosed in 1016 patients (9.8%), all of whom had cirrhosis (49.0% HCC incidence in patients with cirrhosis). HCC was diagnosed at the initial screening in 165 patients (16.2%) and on follow-up in 851 patients (83.8%). The HCC diagnosis median time during follow-up screening was 6 years (range 4−10). Curative-intent treatment (resection, ablation, or transplant) was performed in 713 patients (70.2%). Overall survival at 5 and 10 years in those 713 patients was 30% and 4%, respectively, compared to no 5-year survivors in the 303 patients with advanced-stage disease (p < 0.001). Cause of death at 5 years in the 713 patients treated with curative intent was HCC in 371 patients (52%), progressive cirrhosis in 116 patients (16%), and other causes in 14 patients (2%). At 10 years, 456 patients (64%) had died from HCC, 171 (24%) from progressive cirrhosis, and 57 (8%) from other causes. Conclusions: Our screening program diagnosed early-stage HCC, permitting curative-intent treatment in 70%, but the 10-year survival rate is 4% due to HCC recurrence and progressive cirrhosis.
Collapse
Affiliation(s)
- Francesco Izzo
- Department of Surgical Oncology, IRCCS Fondazione “G. Pascale” National Cancer Institute, 80131 Naples, Italy
| | - Meredith C. Mason
- Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA
| | - Eric J. Silberfein
- Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA
| | - Nader N. Massarweh
- Surgical and Perioperative Care, Atlanta VA Health Care System, Decatur, GA 30033, USA
- Division of Surgical Oncology, Department of Surgery, Emory University School of Medicine, Atlanta, GA 30307, USA
- Department of Surgery, Morehouse School of Medicine, Atlanta, GA 30310, USA
| | - Cary Hsu
- Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA
| | - Hop S. Tran Cao
- Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA
| | - Raffaele Palaia
- Department of Surgical Oncology, IRCCS Fondazione “G. Pascale” National Cancer Institute, 80131 Naples, Italy
| | - Mauro Piccirillo
- Department of Surgical Oncology, IRCCS Fondazione “G. Pascale” National Cancer Institute, 80131 Naples, Italy
| | - Andrea Belli
- Department of Surgical Oncology, IRCCS Fondazione “G. Pascale” National Cancer Institute, 80131 Naples, Italy
| | - Renato Patrone
- Department of Surgical Oncology, IRCCS Fondazione “G. Pascale” National Cancer Institute, 80131 Naples, Italy
| | - Roberta Fusco
- Medical Oncolody Division, Igea SpA, 80013 Naples, Italy
- Italian Society of Medical and Interventional Radiology (SIRM), SIRM Foundation, via della Signora 2, 20122 Milan, Italy
| | - Vincenza Granata
- Division of Radiology, Istituto Nazionale Tumori IRCCS Fondazione Pascale—IRCCS di Napoli, 80131 Naples, Italy
- Correspondence:
| | - Steven A. Curley
- Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA
- Oncology Institute, Christus Trinity Mother Frances Health System, Tyler, TX 75702, USA
| |
Collapse
|
|
8
|
Zahran AM, Zahran ZAM, El-Badawy O, Abdel-Rahim MH, Ali WAM, Rayan A, Abbas El-Masry M, Abozaid MAA, Hetta HF. Prognostic impact of toll-like receptors 2 and 4 expression on monocytes in Egyptian patients with hepatocellular carcinoma. Immunol Res 2020; 67:157-165. [PMID: 31028612 DOI: 10.1007/s12026-019-09075-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Toll-like receptors (TLRs) have a role in chronic inflammation. Still, little is known about the expression of TLRs in hepatocellular carcinoma (HCC). Herein, we tried to assess the prognostic value of TLR2 and TLR4 expression on circulating monocytes in HCC patients and correlate their levels with some clinical, laboratory data, and treatment outcomes. Forty patients with hepatic focal lesions diagnosed radiologically as HCC by triphasic multislice CT pelviabdominal and chest, and in some patients MRI diffusion and 38 age and sex matching healthy controls were enrolled in the study. Subjects were evaluated for liver functions, alpha-fetoprotein (AFP), imaging, response to different treatments, and overall survival. TLR2 and TLR4 expression by monocytes was detected by flow cytometry. The expression of both TLR2 and TLR4 on monocytes was significantly increased in HCC patients than the controls, in patients with more progressive HCC than those with lower progression and in patients with poor response to treatment than patients with better treatment response. Moreover, their levels showed positive correlations with ALT, AST, and AFP and inverse correlations with the overall survival of HCC patients. The results of the current study suggest that increased expression ofTLR2 and TLR4 on peripheral monocytes might reflect the development and progression of HCC and can be used to indicate poor prognosis. In addition, high expression of TLR2 correlated significantly with poor response to treatment, while high expression of both TLR2 and TLR4 were associated with poor survival. Our findings will help to design more studies on the role of TLRs in HCC pathogenesis and prognosis which may provide new therapeutic targets for HCC.
Collapse
Affiliation(s)
- Asmaa M Zahran
- Department of Clinical Pathology, South Egypt Cancer Institute, Assiut University, Assiut, Egypt
| | | | - Omnia El-Badawy
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Mona H Abdel-Rahim
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Wageeh A M Ali
- Departmentof Radiodiagnosis, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Amal Rayan
- Departmentof Clinical Oncology, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Muhammad Abbas El-Masry
- Department of internal Medicine, Division of gastroenterology, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Mohamed A A Abozaid
- Department of internal Medicine, Division of gastroenterology, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Helal F Hetta
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut, Egypt. .,Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, 45267-0595, USA.
| |
Collapse
|
|
9
|
Hassanipour S, Vali M, Gaffari-Fam S, Nikbakht HA, Abdzadeh E, Joukar F, Pourshams A, Shafaghi A, Malakoutikhah M, Arab-Zozani M, Salehiniya H, Mansour-Ghanaei F. The survival rate of hepatocellular carcinoma in Asian countries: a systematic review and meta-analysis. EXCLI JOURNAL 2020; 19:108-130. [PMID: 32038120 PMCID: PMC7003639 DOI: 10.17179/excli2019-1842] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/23/2019] [Accepted: 11/19/2019] [Indexed: 12/18/2022]
Abstract
Hepatocellular carcinoma or Liver cancer (LC) is the sixth most common cancer and the fourth cause of death worldwide in 2018. There has not been a comprehensive study on the survival rate of patients with LC in Asia yet. Therefore, the present study was conducted to evaluate the survival rate of patients with LC in Asian countries. The methodology of the present study is based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) statement. The researchers searched five international databases including Medline/PubMed, Scopus, Embase, Web of Knowledge and ProQuest until July 1, 2018. We also searched Google Scholar for detecting grey literature. The Newcastle-Ottawa Quality Assessment Form was used to evaluate the quality of selected papers. A total of 1425 titles were retrieved. 63 studies met the inclusion criteria. Based on the random-effect model one-year, three-year and five-year survival rate of LC were 34.8 % (95 % CI; 30.3-39.3), 19 % (95 % CI ; 18.2-21.8) and 18.1 % (95 % CI ;16.1-20.1) respectively. According to the results of our study, the LC survival rate in Asian countries is relatively lower than in Europe and North America.
Collapse
Affiliation(s)
- Soheil Hassanipour
- GI Cancer Screening and Prevention Research Center, Guilan University of Medical Sciences, Rasht, Iran.,Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran
| | - Mouhebat Vali
- Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Saber Gaffari-Fam
- Road Traffic Injury Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hossein-Ali Nikbakht
- Social Determinants of Health Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Elham Abdzadeh
- GI Cancer Screening and Prevention Research Center, Guilan University of Medical Sciences, Rasht, Iran
| | - Farahnaz Joukar
- Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran.,Caspian Digestive Disease Research Center, Guilan University of Medical Sciences, Rasht, Iran
| | - Akram Pourshams
- Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran.,Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Afshin Shafaghi
- Caspian Digestive Disease Research Center, Guilan University of Medical Sciences, Rasht, Iran
| | - Mahdi Malakoutikhah
- Department of Occupational Health, Kashan University of Medical Sciences, Kashan, Iran
| | - Morteza Arab-Zozani
- Social Determinants of Health Research Center, Birjand University of Medical Sciences, Birjand, Iran.,Iranian Center of Excellence in Health Management, School of Management and Medical Informatics, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hamid Salehiniya
- Social Determinants of Health Research Center, Birjand University of Medical Sciences, Birjand, Iran
| | - Fariborz Mansour-Ghanaei
- GI Cancer Screening and Prevention Research Center, Guilan University of Medical Sciences, Rasht, Iran.,Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran.,Caspian Digestive Disease Research Center, Guilan University of Medical Sciences, Rasht, Iran
| |
Collapse
|
|
10
|
Zhang XP, Gao YZ, Jiang YB, Wang K, Chen ZH, Guo WX, Shi J, Zhang YJ, Chen MS, Lau WY, Cheng SQ. A serological scoring system to predict lymph node metastasis in patients with hepatocellular carcinoma. HPB (Oxford) 2019; 21:335-344. [PMID: 30104175 DOI: 10.1016/j.hpb.2018.07.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2018] [Revised: 06/25/2018] [Accepted: 07/09/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND Lymph node metastasis (LNM)has widely been recognized as a poor prognostic indicator for hepatocellular carcinoma (HCC) patients. Preoperative prediction of LNM is important for clinicians to decide on treatment. This study was designed to develop a simple and convenient system to predict LNM. METHODS Consecutive HCC patients who were suspected to have LNM were divided into a training, an internal validation and an external validation cohort. The receiver operating characteristic (ROC) analysis was used to determine the threshold value of the preoperative serological variables. A nomogram visualization system model was then established. RESULT Of the 287 patients, there were 31 patients who had LNM (10.8%), and 21 of 203 patients (10.3%) were in the training cohort and 10 of 84 patients (11.9%) in the internal validation cohort. Sixteen of 176 patients (9.1%) in the external validation cohort had LNM. The serological indices including neutrophil/lymphocyte rate, age, platelet, prothrombin time, and total protein, were included in the nomogram. The areas of the ROC curve were 0.846, 0.679 and 0.738 in predicting LNM in the training cohort, the internal validation cohort and the external validation cohort, respectively. CONCLUSION The scoring system constructed using the preoperative serological variables predicted LNM in HCC patients.
Collapse
Affiliation(s)
- Xiu-Ping Zhang
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Yu-Zhen Gao
- Department of Molecular Diagnosis, Clinical Medical College, Yangzhou University, China
| | - Ya-Bo Jiang
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Kang Wang
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Zhen-Hua Chen
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Wei-Xing Guo
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Jie Shi
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Yao-Jun Zhang
- Department of Hepatobiliary Oncology of Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Min-Shan Chen
- Department of Hepatobiliary Oncology of Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Wan Y Lau
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China; Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China
| | - Shu-Qun Cheng
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
| |
Collapse
|
|
11
|
Gon H, Kido M, Tanaka M, Kinoshita H, Komatsu S, Tsugawa D, Awazu M, Toyama H, Matsumoto I, Itoh T, Fukumoto T. Growth velocity of the portal vein tumor thrombus accelerated by its progression, alpha-fetoprotein level, and liver fibrosis stage in patients with hepatocellular carcinoma. Surgery 2018; 164:1014-1022. [DOI: 10.1016/j.surg.2018.06.025] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2018] [Revised: 06/01/2018] [Accepted: 06/12/2018] [Indexed: 12/11/2022]
|
|
12
|
Chang PY, Huang CC, Hung CH, Yu CY, Wu DK, Hwang JI, Liang PC, Wu RH, Tsai WL, Lin YJ, Liu YS, Liang HL, Lee RC, Chen CH. Multidisciplinary Taiwan Consensus Recommendations for the Use of DEBDOX-TACE in Hepatocellular Carcinoma Treatment. Liver Cancer 2018; 7:312-322. [PMID: 30488021 PMCID: PMC6249590 DOI: 10.1159/000487608] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2017] [Accepted: 02/11/2018] [Indexed: 02/04/2023] Open
Abstract
Transarterial chemoembolization (TACE) is the first-line treatment in patients with unresectable hepatocellular carcinoma (HCC). In recent years, there has been increasing clinical evidence that drug-eluting beads provide a combined ischemic and cytotoxic effect that may be superior to conventional TACE, with low systemic toxicity. The therapeutic value of TACE performed using the embolic microsphere DC Bead loaded with doxorubicin (drug-eluting bead doxorubicin [DEBDOX]) has been shown by several randomized controlled trials. Since Lencioni et al. [Cardiovasc Intervent Radiol 2012; 35: 980-985] published the first widely accepted technical recommendations on HCC embolization with DEBDOX-TACE in 2012, new studies have contributed to a better understanding of when and how to apply this new therapeutic modality, and they have yet to be incorporated into an updated guideline. Additionally, differences in the underlying liver pathology and practice of transcatheter embolization between Asian and Western populations have not been adequately addressed, and there remain significant variations in the TACE protocols adopted in different parts of the world. These mainly revolve around the number and type of chemotherapeutic agents used, type of embolic material, reliance on Lipiodol, and selectivity of catheter positioning. As a result of these issues, it has been difficult to interpret and compare results obtained from different centers in a systematic fashion. To address these concerns, we convened a panel of experts specializing in different aspects of HCC treatment to craft an updated set of recommendations that better reflect recent clinical experiences and are tailored to the use of DEBDOX-TACE in Taiwan. The conclusions of this expert panel are described in the following article.
Collapse
Affiliation(s)
- Pi-Yi Chang
- Department of Radiology, Taichung Veterans General Hospital, Taichung City, Taiwan
| | - Chun-Chieh Huang
- Department of Radiology, Far Eastern Memorial Hospital, Taipei, Taiwan
| | - Chao-Hung Hung
- Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung City, Taiwan
| | - Chih-Yung Yu
- Department of Radiology, Tri-Service General Hospital, Taipei, Taiwan
| | - Ding-Kwo Wu
- Department of Radiology, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung City, Taiwan
| | - Jen-I Hwang
- Department of Radiology, Tungs' Taichung Metro Harbor Hospital, Taichung City, Taiwan
| | - Po-Chin Liang
- Department of Radiology, National Taiwan University Hospital, Taipei, Taiwan
| | - Reng-Hong Wu
- Department of Radiology, Chi Mei Hospital, Tainan City, Taiwan
| | - Wei-Lun Tsai
- Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung City, Taiwan
| | - Yih-Jyh Lin
- Department of Surgery, National Cheng Kung University Hospital, Tainan City, Taiwan
| | - Yi-Sheng Liu
- Department of Diagnostic Radiology, National Cheng Kung University Hospital, Tainan City, Taiwan
| | - Huei-Lung Liang
- Department of Radiology, Kaohsiung Veterans General Hospital, Kaohsiung City, Taiwan
| | - Rheun-Chuan Lee
- Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Chien-Hung Chen
- Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch and National Taiwan University College of Medicine, Douliu City, Taiwan,*Chien-Hung Chen, MD, PhD, Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, and National Taiwan University College of Medicine, No. 579, Sec. 2, Yunlin Road, Douliu City, Yunlin County 640 (Taiwan), E-Mail
| |
Collapse
|
|
13
|
Chen KD, Lin CC, Tsai MC, Huang KT, Chiu KW. Tumor microenvironment mediated by suppression of autophagic flux drives liver malignancy. Biomed J 2018; 41:163-168. [PMID: 30080656 PMCID: PMC6138774 DOI: 10.1016/j.bj.2018.03.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2017] [Revised: 03/23/2018] [Accepted: 03/26/2018] [Indexed: 01/10/2023] Open
Abstract
The physiological role of autophagy in the catabolic process of the body involves protein synthesis and degradation in homeostasis under normal and stressed conditions. In hepatocellular carcinoma (HCC), the role of tumor microenvironment (TME) has been concerned as the main issue in fighting against this deadly malignancy. During the last decade, the crosstalk between tumor cells and their TME in HCC extensively accumulated. However, a deeper knowledge for the actual function of autophagy in this interconnection which involved in supporting tumor development, progression and chemoresistance in HCC is needed but still largely unknown. Recent studies have shown that coagulants tissue factor (TF) and factor VII (FVII) has a pathological role in promoting tumor growth by activating protease-activated receptor 2 (PAR2). Autophagy-associated LC3A/B-II formation was selectively suppressed by FVII/PAR2 signaling which mediated by mTOR activation through Atg7 but not Atg5/Atg12 axis. The coagulant-derived autophagic suppression seemed potentiate a vicious circle of malignancy in producing more FVII and PAR2 which facilitate in vivo and in vitro tumor progression of HCC and the investigations are consistent with the clinical observations. In this review, we briefly summarize the current understanding of autophagy and discuss recent evidence for its role in HCC malignancy.
Collapse
Affiliation(s)
- Kuang-Den Chen
- Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
| | - Chih-Che Lin
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Ming-Chao Tsai
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Kuang-Tzu Huang
- Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - King-Wah Chiu
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| |
Collapse
|
|
14
|
Chen Y, Wu Y, Zhang X, Zeng H, Liu Y, Wu Q, Chen Y, Zhu G, Pan Q, Jin L, Guo L, Sun F. Angiopoietin-2 (Ang-2) is a useful serum tumor marker for liver cancer in the Chinese population. Clin Chim Acta 2018; 478:18-27. [PMID: 29253494 DOI: 10.1016/j.cca.2017.12.017] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2017] [Revised: 11/22/2017] [Accepted: 12/12/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND We estimated the diagnostic and prognostic value of serum angiopoietin-2 (Ang-2) in liver cancer patients. METHODS Tissue Ang-2 was measured using immunohistochemistry (IHC). Cell localization of Ang-2 was tested using immunofluorescence (IF). Cell viability and apoptosis were evaluated using MTT and caspase3/7 assays, respectively. Colony-formation was measured using a soft agar assay. Serum Ang-2 was examined using enzyme-linked immunosorbent assay (ELISA) and Western blotting. RESULTS Ang-2 was up-regulated in liver cancer compared to the levels in normal tissues. Serum Ang-2 concentrations were much higher in liver cancer patients than in healthy individuals and those with chronic liver disease (CLD). Inhibitions of Ang-2 using specific shRNA decreased cell proliferation. Serum Ang-2 decreased significantly after surgery. Serum Ang-2 was positively correlated with serum alpha-fetoprotein (AFP; R=0.375, P=0.005). Receiver operating characteristic (ROC) curves suggested that serum Ang-2 could be used with relatively high sensitivity and specificity in differentiating liver cancer patients from CLD patients or healthy controls, with corresponding AUC values of 0.742 and 0.924, respectively. Serum Ang-2 was negatively correlated with overall survival. Subgroup analysis also showed that Ang-2 retained its prognostic value in overall survival prediction in different risk subgroups. CONCLUSION Serum Ang-2 may be a useful tumor marker in predicting liver cancer prognosis.
Collapse
Affiliation(s)
- Yuxin Chen
- Department of Clinical Laboratory, Shanghai Tenth People's Hospital of Tongji University, Shanghai 200072, China
| | - Yanping Wu
- Department of Geriatrics, Zhong Da Hospital of Southeast University, Nanjing 210009, China
| | - Xiao Zhang
- Department of Clinical Laboratory, Shanghai Tenth People's Hospital of Tongji University, Shanghai 200072, China
| | - Hong Zeng
- Department of Pathology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China
| | - Ya Liu
- Department of Clinical Laboratory, Shanghai Tenth People's Hospital of Tongji University, Shanghai 200072, China
| | - Qi Wu
- Department of Clinical Laboratory, Shanghai Tenth People's Hospital of Tongji University, Shanghai 200072, China
| | - Yan Chen
- Department of Clinical Laboratory, Shanghai Tenth People's Hospital of Tongji University, Shanghai 200072, China
| | - GuoQing Zhu
- Department of Clinical Laboratory, Shanghai Tenth People's Hospital of Tongji University, Shanghai 200072, China
| | - Qiuhui Pan
- Department of Laboratory Medicine, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai 200127,China
| | - Lei Jin
- College of Allied Health Professions, Shanghai University of Medicine and Health Sciences, 279 Zhouzhu Highway, Pudong New Area, Shanghai 201318, China.
| | - Lin Guo
- Department of Clinical Laboratory, Shanghai Cancer Center, Fudan University, China; Department of Oncology, Shanghai Medical School, Fudan University, Shanghai 200032, China..
| | - Fenyong Sun
- Department of Clinical Laboratory, Shanghai Tenth People's Hospital of Tongji University, Shanghai 200072, China.
| |
Collapse
|
|
15
|
Ahn HS, Han SH, Kim YH, Park BJ, Kim DH, Lee JB, Park SY, Song CS, Lee SW, Choi C, Myoung J, Choi IS. Adverse fetal outcomes in pregnant rabbits experimentally infected with rabbit hepatitis E virus. Virology 2017; 512:187-193. [PMID: 28982029 DOI: 10.1016/j.virol.2017.09.020] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2017] [Revised: 08/29/2017] [Accepted: 09/22/2017] [Indexed: 01/16/2023]
Abstract
Hepatitis E virus (HEV) causes severe hepatitis in pregnant women, with associated poor fetal outcomes. To study HEV viral pathogenesis, pregnant rabbits were infected with low- and high-dose rabbit HEV at 2 weeks gestation. HEV was identified in the serum, feces, and liver tissue of infected rabbits, and dose-dependent fetal mortality rates ranging from 67% to 80% were observed. The aspartate transaminase (AST)/alanine transaminase ratio was significantly higher (P < 0.01) in high-dose infected rabbits than low-dose infected and negative control rabbits 14 days post infection (dpi). Tumor necrosis factor-α (TNF-α) was significantly higher in low-dose (P < 0.01) and high-dose infected rabbits (P < 0.001) than in negative controls 7 dpi. High-dose HEV-infected rabbits produced significantly more interferon-γ (IFN-γ; P < 0.05) than negative control rabbits at 7 and 14 dpi. High levels of AST, TNF-α, and IFN-γ may substantially influence adverse fetal outcomes in pregnant rabbits infected with high-dose HEV.
Collapse
Affiliation(s)
- Hee-Seop Ahn
- Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea
| | - Sang-Hoon Han
- Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea
| | - Yong-Hyun Kim
- Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea
| | - Byung-Joo Park
- Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea
| | - Dong-Hwi Kim
- Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea
| | - Joong-Bok Lee
- Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea
| | - Seung-Yong Park
- Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea
| | - Chang-Seon Song
- Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea
| | - Sang-Won Lee
- Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea
| | - Changsun Choi
- Department of Food and Nutrition, School of Food Science and Technology, Chung-Ang University, Ansung 17546, Republic of Korea
| | - Jinjong Myoung
- Korea Zoonosis Research Institute, Chonbuk National University, Jeonju 54896, Republic of Korea
| | - In-Soo Choi
- Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea.
| |
Collapse
|
|
16
|
Waziry R, Grebely J, Amin J, Alavi M, Hajarizadeh B, George J, Matthews GV, Law M, Dore GJ. Survival following hospitalization with hepatocellular carcinoma among people notified with hepatitis B or C virus in Australia (2000-2014). Hepatol Commun 2017; 1:736-747. [PMID: 29404490 PMCID: PMC5678911 DOI: 10.1002/hep4.1073] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2017] [Revised: 06/27/2017] [Accepted: 06/29/2017] [Indexed: 12/23/2022] Open
Abstract
We assessed trends in HCC survival in patients with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection in New South Wales, Australia. Data on HBV (n = 54,399) and HCV (n = 96,908) notifications (1993‐2012) were linked to a hospitalization database (July 2000‐June 2014), the New South Wales Cancer Registry, and the New South Wales Death Registry. A total of 725 (1.3%) first HBV‐hepatocellular carcinoma (HCC) and 1,309 (1.4%) first HCV‐HCC hospitalizations were included. Death occurred in 60.4% of HBV‐HCC and 69.6% of HCV‐HCC patients. Median survival following first HBV‐HCC hospitalization improved from 0.6 years (95% confidence interval [CI] 0.39‐1.28) in 2000‐2004 to 2.8 years (1.54‐5.54) in 2010‐2014. Median survival following first HCV‐HCC hospitalization was 0.8 years (0.45‐1.33) in 2000‐2004 and 0.9 (0.67‐1.18) in 2010‐2014. One‐year HBV‐HCC survival in 2010‐2014 compared to 2000‐2004 improved for those with (94% versus 81%) and without (42% versus 33%) potentially curative procedures (liver resection, liver transplantation, and radiofrequency ablation). Factors associated with improved survival following HBV‐HCC were later study period (hazard ratio [HR] = 0.74; 95% CI, 0.57‐0.97) and potentially curative procedures (liver resection, liver transplantation, and radiofrequency ablation) (HR = 0.23; 95% CI, 0.17‐0.29), while male gender (HR = 1.37; 95% CI, 1.03‐1.82), human immunodeficiency virus coinfection (HR = 3.06; 95% CI, 1.36‐6.88), and Charlson Comorbidity Index ≥3 (HR = 1.81; 95% CI, 1.35‐2.40) were associated with reduced survival. Factors associated with improved survival following HCC‐HCV were Asia‐Pacific country of birth (HR = 0.68; 95% CI, 0.55‐0.84) and potentially curative procedures (HR = 0.21; 95% CI, 0.17‐0.25), while age (HR = 1.01; 95% CI, 1.01‐1.02), rural place of residence (HR = 1.46; 95% CI, 1.22‐1.74), and human immunodeficiency virus coinfection (HR = 2.71; 95% CI, 1.19‐6.15) were associated with reduced survival. Conclusion: All‐cause survival following HBV‐HCC has improved considerably, suggesting an impact of more effective antiviral therapy and earlier HCC diagnosis; in contrast, all‐cause survival for HCV‐HCC is unchanged. (Hepatology Communications 2017;1:736–747)
Collapse
Affiliation(s)
- Reem Waziry
- The Kirby Institute UNSW Sydney Sydney Australia
| | | | - Janaki Amin
- Faculty of Medicine and Health Sciences Macquarie University Sydney Australia
| | - Maryam Alavi
- The Kirby Institute UNSW Sydney Sydney Australia
| | | | - Jacob George
- Storr Liver Unit Westmead Millennium Institute and Westmead Hospital, University of Sydney Sydney Australia
| | | | - Matthew Law
- The Kirby Institute UNSW Sydney Sydney Australia
| | | |
Collapse
|
|
17
|
Surgical Resection of Metachronous Lymph Node Metastasis From Hepatocellular Carcinoma: Three Case Reports and Review of the Literature. Int Surg 2017. [DOI: 10.9738/intsurg-d-15-00114.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
The prognosis for hepatocellular carcinoma (HCC) patients with lymph node (LN) metastasis is generally poor, and no consensus has yet been reached on the optimum treatment strategy. We observed 3 cases involving patients with HCC and associated metachronous LN metastasis, who benefited from surgical resection of the metastatic LNs. Each of the 3 patients had solitary LN metastasis for which selective LN resection was performed, and all had C-type cirrhosis as a background disease. There were no other uncontrolled lesions at the time of LN resection. However, additional treatments were required in cases 1 and 3 to control intrahepatic lesions that recurred following the lymphadenectomy. The overall survival in cases 1 and 3 has been >5 years, with case 1 still under observation. Case 2 also remains under follow-up at 6 months after surgery. Surgical resection could be a beneficial strategy for treatment of metachronous LN metastasis arising from HCC in some cases, particularly those involving a solitary LN metastasis with no other uncontrolled lesions.
Collapse
|
|
18
|
Fukumoto T, Kido M, Takebe A, Tanaka M, Kinoshita H, Kuramitsu K, Komatsu S, Tsugawa D, Goto T, Asari S, Toyama H, Ajiki T, Ku Y. New macroscopic classification and back-flow thrombectomy for advanced hepatocellular carcinoma with portal vein tumor thrombus invading the contralateral second portal branch. Surg Today 2017; 47:1094-1103. [PMID: 28324163 DOI: 10.1007/s00595-017-1507-9] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2016] [Accepted: 01/10/2017] [Indexed: 12/13/2022]
Abstract
PURPOSE Patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) invading the portal trunk (Vp4) are poor surgical candidates because of the technical difficulties involved. To overcome the limitations, we developed a technique of back-flow thrombectomy (BFT) based on the inherent portal hemodynamics and the macroscopic form of PVTT. METHODS Forty-six patients with multiple HCC and Vp4 PVTT underwent hepatectomy with tumor thrombectomy. We used the BFT to treat 24 patients, 18 of whom had PVTT in the contralateral second portal branch. The form of PVTT was classified macroscopically into the floating and expansive types. RESULTS The rate of complete removal by BFT of PVTT in the contralateral second portal branch was 89%. The patency rates at the thrombectomy site in all 46 patients and in the 24 BFT patients, 3 months after hepatectomy were 93 and 90%, respectively. The median OS of all 46 patients was 15 months, with 1- and 3-year OS rates of 58.5 and 17.1%, respectively. The median OS of the 24 patients treated with BFT vs. the 22 not treated with BFT was 14 and 15 months, respectively. CONCLUSIONS BFT can expand the therapeutic time window for patients with HCC and deep-seated PVTT and may improve their survival.
Collapse
Affiliation(s)
- Takumi Fukumoto
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
| | - Masahiro Kido
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Atsushi Takebe
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Motofumi Tanaka
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Hisoka Kinoshita
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Kaori Kuramitsu
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Shohei Komatsu
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Daisuke Tsugawa
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Tadahiro Goto
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Sadaki Asari
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Hirochika Toyama
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Tetsuo Ajiki
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Yonson Ku
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| |
Collapse
|
|
19
|
Bauschke A, Altendorf-Hofmann A, Malessa C, Schüle S, Zanow J, Settmacher U. Which factors affect the long-term survival of patients with hepatocellular carcinoma UICC stage IV? J Cancer Res Clin Oncol 2016; 142:2593-2601. [PMID: 27630023 DOI: 10.1007/s00432-016-2260-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2016] [Accepted: 09/06/2016] [Indexed: 12/14/2022]
Abstract
AIM In the 7th edition of the TNM classification, not only HCC with distant metastases but also those with regional lymph node metastases are classified as stage IV. MATERIALS AND METHODS, RESULTS From our prospectively recorded tumor registry, 138 patients (17 %) with HCC were in stage IV. Among those were 68 and 70, respectively, in stage IVA (regional lymph node metastases) and IVB (distant metastases). The tumors were less frequently treated with resection or local ablative treatment (chemoembolization, RFA, SIRT, percutaneous radiation) than patients in stage I-III. Ten HCCs were resected. Five of the resected patients were in stage IVA and five in stage IVB. After tumor resection, patients lived longer than those who underwent local or systemic treatment only (p = 0.003 or p = 0.001, respectively). In the univariate survival analysis, the stage IV patients' long-term survival was decreased statistically significantly through elevated bilirubin, low albumin, Okuda stage III and BCLC stage D. Patients' age and sex, pre-treatment AFP level, Child stage and the presence of venous invasion did not influence survival. In the multivariate analysis (Cox regression), tumor resection and BCLC stage were independent prognostic factors. CONCLUSION Patients with HCC in TNM stage IV have a very poor prognosis. Only few patients are eligible for resection because of the extent of tumor growth, comorbidities and general condition. These, however, benefit markedly from tumor resection with lymph node dissection and possibly resection of distant metastases.
Collapse
Affiliation(s)
- A Bauschke
- Department of General, Visceral and Vascular Surgery, University Hospital Jena, Erlanger Allee 101, 07740, Jena, Germany.
| | - A Altendorf-Hofmann
- Department of General, Visceral and Vascular Surgery, University Hospital Jena, Erlanger Allee 101, 07740, Jena, Germany
| | - C Malessa
- Department of General, Visceral and Vascular Surgery, University Hospital Jena, Erlanger Allee 101, 07740, Jena, Germany
| | - S Schüle
- Department of General, Visceral and Vascular Surgery, University Hospital Jena, Erlanger Allee 101, 07740, Jena, Germany
| | - J Zanow
- Department of General, Visceral and Vascular Surgery, University Hospital Jena, Erlanger Allee 101, 07740, Jena, Germany
| | - U Settmacher
- Department of General, Visceral and Vascular Surgery, University Hospital Jena, Erlanger Allee 101, 07740, Jena, Germany
| |
Collapse
|
|
20
|
Kee KM, Wang JH, Wang CC, Cheng YF, Lu SN. Hepatocellular Carcinoma associated with Extra-hepatic Primary Malignancy: its Secular change, Clinical Manifestations and Survival. Sci Rep 2016; 6:30156. [PMID: 27444261 PMCID: PMC4957107 DOI: 10.1038/srep30156] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2015] [Accepted: 06/29/2016] [Indexed: 12/17/2022] Open
Abstract
Clinical manifestations between hepatocellular carcinoma (HCC) and extra-hepatic primary malignancy (EHPM) are lack of large-scale study. We enrolled 14555 HCC patients between 1986 and 2013 retrospectively. The EHPM was classified as prior, synchronous and metachronous group based on before, within and after 6 months of HCC diagnosis, respectively. The incidence rate of EHPM is 3.91% (95% confidence interval [CI]: 3.60–4.23%). Urogenital cancers, kidney and bladder, were at unexpected higher ranks. Older in age, Child-Pugh A cirrhosis, negativity of HBsAg and anti-HCV, and earlier BCLC staging are independent factors associated with EHPM. The survival rates of EHPM improve over time and also better than HCC-alone. Cox proportional-hazards regression shows independent poor prognostic factors are age >60, male, AFP levels ≥400 ng/ml, positivity of HBsAg, Child-Pugh B vs. A, Non-metachronous group, respectively, treated with local ablation, transcatheter arterial embolization, radiotherapy and supportive care vs. surgery, respectively, TNM stage IIIA vs. I, and BCLC stages A, B, C and D vs. 0, respectively. Survival of EHPM improve could be explained by early diagnosis and improve treatment of cancers.
Collapse
Affiliation(s)
- Kwong Ming Kee
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Jing-Houng Wang
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chih-Chi Wang
- Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Yu-Fan Cheng
- Department of Radiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Sheng-Nan Lu
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| |
Collapse
|
|
21
|
Yang P, Zeng ZC, Wang BL, Zhang JY, Fan J, Zhou J, Hu Y. The Degree of Lipiodol Accumulation Can Be an Indicator of Successful Treatment for Unresectable Hepatocellular Carcinoma (HCC) Patients - in the Case of Transcatheter Arterial Chemoembolization (TACE) and External Beam Radiotherapy (EBRT). J Cancer 2016; 7:1413-20. [PMID: 27471557 PMCID: PMC4964125 DOI: 10.7150/jca.15405] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2016] [Accepted: 05/18/2016] [Indexed: 01/26/2023] Open
Abstract
PURPOSE Transcatheter arterial chemoembolization (TACE) in combination with external beam radiotherapy (EBRT) results in improved survival due to better local control in patients with unresectable hepatocellular carcinoma (HCC). The purpose of this study was to investigate lipiodol accumulation, as it reflects tumor burden and is a potential prognostic factor, in HCC patients treated with TACE/EBRT. METHODS AND MATERIALS We retrospectively studied 147 patients with unresectable HCC treated with TACE and EBRT. Clinical features, adverse reactions, and prognostic factors were analyzed. All patients were treated with TACE 1-6 times in combination with EBRT (44-66 Gy) in dose of 2 Gy/fraction given once a day five times a week. Tumor status and laboratory findings were followed. The degree of lipiodol accumulation was assessed by computed tomography before EBRT, and was categorized as either complete/intense or low/moderate. RESULTS The response rate of tumor size after EBRT was 68.2%, median survival was 23.1 months, and overall survival rates were 86.6%, 49.2%, and 28.2% at 1, 2, and 3 years, respectively. Univariate analysis showed that lower hemoglobin levels, higher alkaline phosphatase levels, Child-Pugh B, negative alpha-fetoprotein (AFP) response after EBRT, poor treatment response after EBRT, tumor diameter >10 cm, and poor lipiodol accumulation were unfavorable prognostic factors. On multivariate analysis, higher hemoglobin levels, Child-Pugh A, decreased AFP levels after treatment, Helical Tomotherapy (HT) and intense lipiodol accumulation after TACE were significant favorable predictors. CONCLUSIONS The degree of lipiodol accumulation before EBRT is a prognostic factor in patients with unresectable HCC. Increased AFP levels after EBRT are always associated with poor survival. HT is recommended as a potentially better EBRT modality than three-dimensional conformal radiation therapy (3D-CRT).
Collapse
Affiliation(s)
- Ping Yang
- 1. Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Zhao-Chong Zeng
- 1. Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Bin-Liang Wang
- 1. Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Jian-Ying Zhang
- 1. Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Jia Fan
- 2. Department of Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Jian Zhou
- 2. Department of Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Yong Hu
- 1. Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| |
Collapse
|
|
22
|
Hsiao WD, Peng CY, Chuang PH, Lai HC, Cheng KS, Chou JW, Chen YY, Yu CJ, Feng CL, Su WP, Chen SH, Kao JT. Evaluation of dose-efficacy of sorafenib and effect of transarterial chemoembolization in hepatocellular carcinoma patients: a retrospective study. BMC Gastroenterol 2016; 16:50. [PMID: 27117280 PMCID: PMC4847248 DOI: 10.1186/s12876-016-0464-x] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2015] [Accepted: 04/15/2016] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND Transarterial chemoembolization (TACE) and sorafenib are the therapeutic standard for intermediate and advanced stage hepatocellular carcinoma (HCC) patients respectively. High costs with adverse events (AE) of sorafenib might limit sorafenib dosage, further affecting therapeutic response. To attain greatest benefit, we evaluated the efficacy of different doses and effect of TACE during and after sorafenib discontinuation in patients representing Child-Pugh Classification Class A with venous or extra-hepatic invasion. METHODS A total 156 patients met the criteria and were divided into Groups I (n = 52) accepting 800 mg/day; II (n = 58) accepting 800 mg/day and reduced to 400 mg/day owing to AE; and III (n = 46) accepting 400 mg/day. TACE was performed during and after sorafenib discontinuation and therapeutic response bimonthly to four-monthly was rated thereafter. RESULTS Median duration of sorafenib treatment and patients' survival were 4.00 ± 0.45 and 7.50 ± 1.44 months in all cases; 2.50 ± 0.90 and 5.00 ± 1.10 months in Group I; 5.50 ± 1.27 and 16.50 ± 1.86 months in Group II; 4.00 ± 0.94 and 6.50 ± 2.49 months in Group III. Group II presented the best response and survival benefit (p = 0.010 and p = 0.011 respectively). Child-Pugh Classification score 5 (Hazard Ratio = 0.492, p = 0.049), absent AE (3.423, p = 0.015), tumor numbers ≤ 3 (0.313, p = 0.009), sorafenib duration ≤ 1 cycle (3.694, p = 0.004), and absent TACE (3.197, p = 0.008) significantly correlated with patient survival. TACE benefit appeared in separate and total cases during (p = 0.002, p = 0.595, p = 0.074, p = 0.002 respectively) and after discontinuation of sorafenib administration (p = 0.001, p = 0.034, p = 0.647, p = 0.001 respectively). CONCLUSIONS Low-dosage sorafenib not only appeared tolerable and lowered economic pressure but also provided satisfactory results. TACE benefited patient's survival during and after sorafenib discontinuation.
Collapse
Affiliation(s)
- Wang-De Hsiao
- Division of Hepato-Gastroenterology, Department of Internal Medicine, China Medical University Hospital, No. 2, Yuh-Der Road, Taichung, 404, Taiwan
| | - Cheng-Yuan Peng
- School of Medicine, China Medical University, Taichung, Taiwan
- Division of Hepato-Gastroenterology, Department of Internal Medicine, China Medical University Hospital, No. 2, Yuh-Der Road, Taichung, 404, Taiwan
| | - Po-Heng Chuang
- Division of Hepato-Gastroenterology, Department of Internal Medicine, China Medical University Hospital, No. 2, Yuh-Der Road, Taichung, 404, Taiwan
| | - Hsueh-Chou Lai
- Division of Hepato-Gastroenterology, Department of Internal Medicine, China Medical University Hospital, No. 2, Yuh-Der Road, Taichung, 404, Taiwan
| | - Ken-Sheng Cheng
- Division of Hepato-Gastroenterology, Department of Internal Medicine, China Medical University Hospital, No. 2, Yuh-Der Road, Taichung, 404, Taiwan
| | - Jen-Wei Chou
- Division of Hepato-Gastroenterology, Department of Internal Medicine, China Medical University Hospital, No. 2, Yuh-Der Road, Taichung, 404, Taiwan
| | - Yang-Yuan Chen
- School of Medicine, China Medical University, Taichung, Taiwan
- Division of Hepato-Gastroenterology, Department of Internal Medicine, China Medical University Hospital, No. 2, Yuh-Der Road, Taichung, 404, Taiwan
| | - Cheng-Ju Yu
- Division of Hepato-Gastroenterology, Department of Internal Medicine, China Medical University Hospital, No. 2, Yuh-Der Road, Taichung, 404, Taiwan
| | - Chun-Lung Feng
- Division of Hepato-Gastroenterology, Department of Internal Medicine, China Medical University Hospital, No. 2, Yuh-Der Road, Taichung, 404, Taiwan
| | - Wen-Pang Su
- Division of Hepato-Gastroenterology, Department of Internal Medicine, China Medical University Hospital, No. 2, Yuh-Der Road, Taichung, 404, Taiwan
| | - Sheng-Hung Chen
- Division of Hepato-Gastroenterology, Department of Internal Medicine, China Medical University Hospital, No. 2, Yuh-Der Road, Taichung, 404, Taiwan
| | - Jung-Ta Kao
- School of Medicine, China Medical University, Taichung, Taiwan.
- Division of Hepato-Gastroenterology, Department of Internal Medicine, China Medical University Hospital, No. 2, Yuh-Der Road, Taichung, 404, Taiwan.
| |
Collapse
|
|
23
|
Li J, Hou Y, Cai XB, Liu B. Sorafenib after resection improves the outcome of BCLC stage C hepatocellular carcinoma. World J Gastroenterol 2016; 22:4034-4040. [PMID: 27099447 PMCID: PMC4823254 DOI: 10.3748/wjg.v22.i15.4034] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2015] [Revised: 10/27/2015] [Accepted: 12/30/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate whether sorafenib use after resection impacts tumor relapse and survival in Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC).
METHODS: This retrospective study enrolled 36 male BCLC stage C HCC patients with portal vein thrombus and Child-Pugh class A liver function. Twenty-four patients received only surgical resection (SR), and 12 patients received oral sorafenib within 30 d after surgery. The primary outcomes were time to progression (TTP) (the time from surgical resection until HCC recurrence or extrahepatic metastases) and overall survival (OS). The secondary outcome was the rate of postoperative recurrence or metastasis. TTP and OS were analyzed using Kaplan Meier curves.
RESULTS: There were no significant differences between the two groups in the serum levels of alpha-fetoprotein, copies of hepatitis B virus-DNA, preoperative laboratory results, degree of hepatic fibrosis, types of portal vein tumor thrombus, number of satellite lesions, tumor diameter, pathological results, volume of blood loss, volume of blood transfusion, or surgery time (all P > 0.05). Patients in the SR + sorafenib group had a significantly longer TTP (29 mo vs 22 mo, P = 0.041) and a significantly longer median OS (37 mo vs 30 mo, P = 0.01) compared to patients in the SR group. The SR group had 18 cases (75%) of recurrence/metastasis while the SR + sorafenib group had six cases (50%) of recurrence/metastasis. A total of 19 patients died after surgery (five in the SR + sorafenib group and 14 in the SR group). The most common sorafenib-related adverse events were skin reactions, diarrhea, and hypertension, all of which were resolved with treatment.
CONCLUSION: Sorafenib after SR was well-tolerated. Patients who received sorafenib after SR had better outcomes compared to patients who received only SR.
Collapse
|
|
24
|
Yeh JH, Hung CH, Wang JH, Chen CH, Kee KM, Kuo CM, Yen YH, Cheng YF, Chen YY, Hsu HC, Lu SN. Modifiable Prognostic Factors of Hepatocellular Carcinoma in Patients with Non-Surgical Treatment. PLoS One 2015; 10:e0144893. [PMID: 26661388 PMCID: PMC4685988 DOI: 10.1371/journal.pone.0144893] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2015] [Accepted: 11/24/2015] [Indexed: 02/08/2023] Open
Abstract
Background & aims Current hepatocellular carcinoma (HCC) staging systems only use baseline characteristics to predict outcome. We aimed to explore modifiable factors of the prognosis in HCC cases had undergone non-surgical treatment. Methods All HCC cases in Kaohsiung Chang Gung Memorial hospital in southern Taiwan from 2002 to 2012 must met all below criteria: (1) met international diagnostic guidelines, (2) underwent the initial treatments in our hospital (3) treated by non-surgical treatment modalities and (4) survived more than two years, with follow-up time longer than five years. Results A total 698 patients were enrolled: 451 (24.6%, group A) survivied between 2 to 5 years, and 247 (13.5%, group B) had survived > 5 years. Aside from liver function reserve and BCLC stages, four interventional factors: initial treatment modality, outcomes of 1st or 2nd treatment, and anti-viral therapy to chronic viral hepatitis were associated with prognosis. After propensity score matching, multiple logistic regression of 223 well-matched pairs showed that recurrence within one year after 1st treatment (OR: 2.17, 95% CI: 1.35–3.48), incomplete 2nd treatment (2.01, 1.27–3.17) and absence of anti-viral agents (1.68, 1.09–2.59) were independent poor prognostic factors. Conclusion Complete treatment and anti-viral agents to chronic hepatitis were both independent modifiable prognostic factors of HCC patients had undergone non-surgical treatment. Based on these findings, timely treatment to achieve maximal locoregional control and anti-viral treatment should be provided as possible.
Collapse
Affiliation(s)
- Jen-Hao Yeh
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chao-Hung Hung
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Jing-Houng Wang
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chien-Hung Chen
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Kwong-Ming Kee
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chung-Mou Kuo
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Yi-Hao Yen
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Yu-Fan Cheng
- Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Yen-Yang Chen
- Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Hsuan-Chi Hsu
- Department of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Sheng-Nan Lu
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
- * E-mail:
| |
Collapse
|
|
25
|
Pinato DJ, Karamanakos G, Ishizuka M, Smirne C, Pirisi M, Kubota K, Sharma R. The Kings Score refines prognostic prediction in hepatocellular carcinoma: a novel application. Liver Int 2015; 35:2458-65. [PMID: 25845291 DOI: 10.1111/liv.12841] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2014] [Accepted: 03/20/2015] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS There are a number of prognostic scores in hepatocellular carcinoma (HCC), none of which is optimal in predicting overall survival (OS) in the individual patient, particularly in intermediate stage disease, where patients are not surgically treatable but may qualify for a wide range of palliative interventions. We evaluated the prognostic role of a biochemical algorithm, the Kings Score (KS), in the palliative setting of care. METHODS We used the algorithm [age x AST x INR]/platelet count to derive the KS. Full clinical data including Barcelona Clinic Liver Cancer (BCLC) stage were studied in a training set of 97 patients from the UK. Independent predictors of survival identified in multivariate analysis were validated in an independent cohort of 766 patients from Japan and Italy. RESULTS In both training and validation sets, KS was confirmed as an independent predictor of OS (P < 0.01). Ad-hoc subgroup analysis revealed the KS to be prognostic in the palliative setting, being able to subclassify patients presenting with intermediate and advanced disease according to BCLC criteria (P < 0.001). CONCLUSION The KS integrates into the BCLC system to improve prognostic substratification in the palliative setting of care. The KS may help reducing disease heterogeneity and refine treatment allocation in intermediate-advanced HCC.
Collapse
Affiliation(s)
- David J Pinato
- Division of Experimental Medicine, Imperial College London, Hammersmith Hospital, London, UK
| | - Georgios Karamanakos
- Division of Experimental Medicine, Imperial College London, Hammersmith Hospital, London, UK
| | - Mitsuru Ishizuka
- Department of Gastroenterological Surgery, Dokkyo Medical University, Mibu, Tochigi, Japan
| | - Carlo Smirne
- Department of Translational Medicine, Università degli Studi del Piemonte Orientale "A. Avogadro", Novara, Italy
| | - Mario Pirisi
- Department of Translational Medicine, Università degli Studi del Piemonte Orientale "A. Avogadro", Novara, Italy.,Interdisciplinary Research Center of Autoimmune Diseases, Università degli Studi del Piemonte Orientale "A. Avogadro", Novara, Italy
| | - Keiichi Kubota
- Department of Gastroenterological Surgery, Dokkyo Medical University, Mibu, Tochigi, Japan
| | - Rohini Sharma
- Division of Experimental Medicine, Imperial College London, Hammersmith Hospital, London, UK
| |
Collapse
|
|
26
|
Hung CH, Hu TH, Lu SN, Kuo FY, Chen CH, Wang JH, Huang CM, Lee CM, Lin CY, Yen YH, Chiu YC. Circulating microRNAs as biomarkers for diagnosis of early hepatocellular carcinoma associated with hepatitis B virus. Int J Cancer 2015; 138:714-20. [PMID: 26264553 DOI: 10.1002/ijc.29802] [Citation(s) in RCA: 61] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2015] [Revised: 07/22/2015] [Accepted: 07/28/2015] [Indexed: 12/14/2022]
Abstract
Hepatocarcinogenesis is a multistep process that evolves from cirrhosis or dysplastic nodule (DN), and eventually leads to overt hepatocellular carcinoma (HCC). Differentiation between early HCC and DN is an important issue in the clinical setting. This study aims to investigate the potential of circulating microRNA (miRNA) levels in the diagnosis of early HCC. RNA was extracted from sera of 30 chronic hepatitis B patients with pathologically proven DN and 120 age- and sex-matched patients with early HCC. Paired samples were collected from ten patients with DN who developed overt HCC in the follow-up. A panel of ten cancer-associated miRNAs was analyzed by quantitative real-time reverse-transcription polymerase chain reaction. Serum levels of miR-16, miR-122, miR-221, let-7b and miR-15b were significantly lower in patients with DN than in the HCC group. When DN progressed to overt HCC, serum miR-122, miR-let-7b and miR-15b levels increased significantly (p = 0.046, 0.043 and 0.044, respectively). As a single marker, α-fetoprotein (AFP) and miR-122 as well as let-7b had the similar performance for differentiate HCC from DN. As limited to subjects with normal AFP, let-7b resulted in a sensitivity of 84.8% and a specificity of 50% in separating HCC and DN with a cutoff value of 3.5 (p = 0.001). In conclusion, miR-122 and let-7b, which are upregulated in the serum of early-HCC patients, can be useful markers for differentiating early HCC from DN in chronic hepatitis B patients.
Collapse
Affiliation(s)
- Chao-Hung Hung
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Tsung-Hui Hu
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Sheng-Nan Lu
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Fang-Ying Kuo
- Department of Pathology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chien-Hung Chen
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Jing-Houng Wang
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chao-Min Huang
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chuan-Mo Lee
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chih-Yun Lin
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Yi-Hao Yen
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Yi-Chun Chiu
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| |
Collapse
|
|
27
|
A retrospective analysis of cirrhotic patients receiving Chinese herbal medicine in addition to conventional care: Survival and safety. Eur J Integr Med 2015. [DOI: 10.1016/j.eujim.2014.11.003] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
|
|
28
|
Zhu Q, Li N, Zeng X, Han Q, Li F, Yang C, Lv Y, Zhou Z, Liu Z. Hepatocellular carcinoma in a large medical center of China over a 10-year period: evolving therapeutic option and improving survival. Oncotarget 2015; 6:4440-4450. [PMID: 25686836 PMCID: PMC4414202 DOI: 10.18632/oncotarget.2913] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2014] [Accepted: 12/11/2014] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is among the most common and lethal cancers worldwide, especially in China. METHODS We retrospectively analyzed data from patients who were diagnosed and treated HCC between 2002 and 2011 in a large hospital in northwest China and compared the data between periods 2002-2006 (P1) and 2007-2011 (P2). RESULTS 2045 patients were included in analysis. The HCC stages at diagnosis according to the Barcelona clinic liver cancer staging system had no significant change. Treatment options of liver transplantation, transcatheter arterial chemoembolization and other therapy decreased while percutaneous local ablation and supportive care increased from P1 to P2. Options of surgical resection and systematic therapy had no significant change. Patient survival rates at 1, 3 and 5 years significantly improved from P1 to P2. The treatments with increasing option trend had a higher magnitude of survival increase and vise versa. CONCLUSION Over the last 10 years, the patient survival had a significant increase which was mainly a result of the optimal therapeutic selections according to disease stages in this center. However, the proportion of patients diagnosed at early stages of HCC remained low and did not increase, a result calling for implementing surveillance system for at risk patients.
Collapse
Affiliation(s)
- Qianqian Zhu
- Department of Infectious Diseases, First Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, 710061 Shaanxi, China
| | - Na Li
- Department of Infectious Diseases, First Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, 710061 Shaanxi, China
| | - Xiaoyan Zeng
- Department of Laboratory Medicine, First Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, 710061 Shaanxi, China
| | - Qunying Han
- Department of Infectious Diseases, First Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, 710061 Shaanxi, China
| | - Fang Li
- Department of Infectious Diseases, First Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, 710061 Shaanxi, China
| | - Cuiling Yang
- Department of Infectious Diseases, First Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, 710061 Shaanxi, China
| | - Yi Lv
- Department of Hepatobiliary Surgery, First Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, 710061 Shaanxi, China
- Institute of Advanced Surgical Technology and Engineering, Xi’an Jiaotong University, Xi’an, 710061 Shaanxi, China
| | - Zhihua Zhou
- Department of Infectious Diseases, First Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, 710061 Shaanxi, China
| | - Zhengwen Liu
- Department of Infectious Diseases, First Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, 710061 Shaanxi, China
- Institute of Advanced Surgical Technology and Engineering, Xi’an Jiaotong University, Xi’an, 710061 Shaanxi, China
| |
Collapse
|
|
29
|
Liu PH, Hsia CY, Lee YH, Hsu CY, Huang YH, Su CW, Lee RC, Lin HC, Huo TI. Surgical resection versus transarterial chemoembolization for BCLC stage C hepatocellular carcinoma. J Surg Oncol 2015; 111:404-9. [PMID: 25643842 DOI: 10.1002/jso.23854] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2014] [Accepted: 11/08/2014] [Indexed: 01/03/2023]
Abstract
BACKGROUND Sorafenib is the only recommended treatment for patients with Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC). We aimed to compare surgical resection (SR) and transarterial chemoembolization (TACE) for advanced (BCLC stage C) HCC patients. METHODS A total of 264 and 389 advanced HCC patients received SR and TACE, respectively. Among them, 163 matched pairs of patients were identified from each treatment arm by propensity score matching analysis to compare long-term survival. RESULTS Of all patients, the SR group had better liver functional reserve than the TACE group. In the matched propensity model, the baseline characteristics were similar between patients receiving SR and TACE. SR provided significantly better long-term survival than TACE in all patients and in patients selected in the propensity model (both P < 0.001). In the Cox proportional hazards model, patients receiving TACE had a 2.393-fold increased risk of mortality compared with patients receiving SR (95% confidence interval: 1.610-3.556, P < 0.001). CONCLUSIONS SR provides significantly better long-term survival than TACE in patients with BCLC stage C HCC, and should be an integral part in the management of advanced HCC. Multidisciplinary approaches for these patients and further amendment to the BCLC classification scheme are required.
Collapse
Affiliation(s)
- Po-Hong Liu
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan; Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | | | | | | | | | | | | | | | | |
Collapse
|
|
30
|
Abstract
Small hepatocellular carcinomas (HCCs) usually arise in cirrhosis, often with associated thrombocytopenia. Many patients with large HCCs have normal blood platelet counts. In this review, we compare parameter and phenotype patterns of patients with small (≤ 3 cm) and larger HCCs. A retrospective analysis was undertaken of a 4,139-patient HCC database to compare patient demographics, and liver and tumor characteristics associated with small and large HCCs, especially with respect to platelet counts. We found that patients with larger HCCs had more tumor nodules and portal vein thrombosis (PVT) positivity, and had higher blood alpha-fetoprotein (AFP), bilirubin, and platelet counts. In patients with larger tumors and normal platelets (43.7% of the cohort), tumors were larger and AFP levels were higher, with lower bilirubin and aspartate aminotransferase (AST) levels than in patients with larger tumors and thrombocytopenia (17.5%). A parsimonious multinomial regression model showed a high odds ratio for AFP and platelets for tumors>3 cm with PVT. We conclude that platelet levels are associated with distinct large HCC phenotypes.
Collapse
Affiliation(s)
- Brian I Carr
- Department of Liver Tumor Biology, IRCCS S. de Bellis, Castellana Grotte, Italy.
| | - Chih-Yun Lin
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung Memorial Hospital, Kaohsiung Medical Center and Chang Gung University, Kaohsiung, Taiwan
| | - Sheng-Nan Lu
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung Memorial Hospital, Kaohsiung Medical Center and Chang Gung University, Kaohsiung, Taiwan
| |
Collapse
|
|
31
|
Li H, Wu JS, Wang XT, Lv P, Gong LS, Liu G, Tian BN, Li YY, Jiang B. Factors predicting surgical resection in patients with intrahepatic cholangiocarcinoma and cirrhosis. J INVEST SURG 2014; 27:219-25. [PMID: 24476002 DOI: 10.3109/08941939.2014.880138] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
Here, we investigate the potential factors that affect the outcome of patients with intrahepatic cholangiocarcinomas (ICC) and cirrhosis. We retrospectively reviewed the clinical data and pathological features of 58 patients with ICC and cirrhosis who underwent liver resection between July 2000 and March 2008, and analyzed the prognostic risk factors by means of univariate and multivariate analyses. The overall morbidity and mortality were 40% and 3.3%, respectively. The overall median survival was 24 months, and the 1-, 3-, and 5-year actuarial survival rates were 53%, 18%, and 10%, respectively. Univariate analysis showed that Child-Pugh classification, hypoalbuminemia, vascular invasion, lymphnodes metastasis, tumor-nodes-metastasis (TNM) staging system, positive surgical margins, and high perioperative blood transfusion volumes were all significantly associated with poor survival. Multivariate analysis confirmed that hypoalbuminemia, vascular invasion, positive surgical margins, and high perioperative blood transfusion volume were survival related, with hazard ratios (HR) of 2.58, 3.12, 3.57, and 1.98, respectively. Surgical resection is an effective treatment for patients affected by ICC and cirrhosis. Predictive factors, including hypoalbuminemia, vascular invasion, positive surgical margins, and high perioperative blood transfusion volumes are all related to poor survival.
Collapse
Affiliation(s)
- Hao Li
- Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital , Changsha , China
| | | | | | | | | | | | | | | | | |
Collapse
|
|
32
|
Tsai HJ, Hsieh MY, Tsai YC, Liu ZY, Hsieh HY, Lee CM, Chien CH, Chiu YW, Chuang HY, Huang CT. Liver function tests may be useful tools for advanced cancer patient care: a preliminary single-center result. Kaohsiung J Med Sci 2013; 30:146-52. [PMID: 24581215 DOI: 10.1016/j.kjms.2013.09.005] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2013] [Accepted: 05/07/2013] [Indexed: 10/25/2022] Open
Abstract
Accurate prognostication in advanced cancer may facilitate better palliative care. An objective marker may be more applicable and appropriate than a subjective evaluation by physicians. The aim of this study was to evaluate liver function tests as useful prognostic factors for survival in patients with advanced cancer. We recruited advanced cancer patients from January 2007 to December 2009. Data on age, sex, cancer diagnosis, site of metastases, clinical symptoms, and performance status were collected at the time of admission to the palliative care unit. Analyzed laboratory data were obtained on the Day 1 of admission to the palliative care unit. A total of 522 patients were enrolled; 322 (61.7%) of them were males. The mean age was 60.6 ± 13.2 years. Multiple logistic regression analysis adjusting for age and sex demonstrated aspartate transaminase (AST) > 80 IU/L [odds ratio (OR) = 2.01, p = 0.010] and alanine transaminase > 80 IU/L (OR = 1.89, p = 0.047) were independently significant prognostic factors of death within 14 days. AST > 80 IU/L (OR = 3.67, p = 0.017) and albumin < 3.0 g/dL (OR = 1.98, p = 0.048) were independently significant prognostic factors of death within 6 months. Liver function tests may be useful prognostic factors for patients in the palliative care unit, in addition to being useful for patients with hepatobiliary cancer or liver metastasis. These biochemical tests of liver function with cutoff values can easily be used in palliative care.
Collapse
Affiliation(s)
- Hui-Ju Tsai
- Department of Family Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan
| | - Ming-Yen Hsieh
- Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan; Faculty of Medicine, Kaohsiung Medical University, Taiwan
| | - Yi-Chun Tsai
- Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Medicine, Kaohsiung Medical University, Taiwan
| | - Zi-Yun Liu
- Department of Nursing, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Hui-Ya Hsieh
- Department of Nursing, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chiou-Mei Lee
- Department of Family Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ching-Hsin Chien
- Department of Nursing, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yu-Wen Chiu
- Department of Family Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan; Faculty of Medicine, Kaohsiung Medical University, Taiwan
| | - Hung-Yi Chuang
- Department of Family Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Public Health, Kaohsiung Medical University, Kaohsiung, Taiwan.
| | - Chia-Tsuan Huang
- Department of Family Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Faculty of Medicine, Kaohsiung Medical University, Taiwan
| |
Collapse
|
|
33
|
Izzo F, Piccirillo M, Albino V, Palaia R, Belli A, Granata V, Setola S, Fusco R, Petrillo A, Orlando R, Tosone G, Scordino F, Curley SA. Prospective screening increases the detection of potentially curable hepatocellular carcinoma: results in 8,900 high-risk patients. HPB (Oxford) 2013; 15:985-90. [PMID: 23607636 PMCID: PMC3843617 DOI: 10.1111/hpb.12080] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2012] [Accepted: 01/21/2013] [Indexed: 02/06/2023]
Abstract
OBJECTIVES Historically, only 10% of patients with hepatocellular carcinoma (HCC) are diagnosed with early-stage, potentially curable disease. In this study, chronic hepatitis virus-infected patients were prospectively screened to determine: (i) the proportion of patients diagnosed with potentially curable HCC, and (ii) survival following curative therapy. METHODS The study included 8900 chronic hepatitis virus-infected patients enrolled in a prospective screening programme, of whom 1335 (15.0%) were infected with hepatitis B virus (HBV), 7120 (80.0%) with hepatitis C virus (HCV), and 445 (5.0%) with both HBV and HCV. Screening was conducted every 6 months and included serum alpha-fetoprotein (AFP) measurement and ultrasonography. Curative treatments included liver transplantation, resection, radiofrequency ablation and/or ethanol injection. RESULTS Hepatocellular carcinoma was diagnosed in 765 (8.6%) patients. Of 1602 patients with cirrhosis, 758 (47.3%) developed HCC. Curative treatment was possible in 523 (68.4%) of the 765 HCC patients. Two- and 5-year rates of overall survival in the curative treatment group were 65% and 28%, respectively, compared with 10% and 0% in the advanced disease group (P < 0.001). CONCLUSIONS Prospective screening of patients at high risk for the development of HCC increases the proportion of patients diagnosed with potentially curable disease. This may result in an increase in the number of longterm survivors. Screening strategies should focus on patients with chronic HBV or HCV infection who have progressed to cirrhosis because more than 40% of these patients will develop HCC.
Collapse
Affiliation(s)
- Francesco Izzo
- Division of Surgical Oncology, G. Pascale National Cancer InstituteNaples, Italy
| | - Mauro Piccirillo
- Division of Surgical Oncology, G. Pascale National Cancer InstituteNaples, Italy
| | - Vittorio Albino
- Division of Surgical Oncology, G. Pascale National Cancer InstituteNaples, Italy
| | - Raffaele Palaia
- Division of Surgical Oncology, G. Pascale National Cancer InstituteNaples, Italy
| | - Andrea Belli
- Division of Surgical Oncology, G. Pascale National Cancer InstituteNaples, Italy
| | - Vincenza Granata
- Department of Radiology, G. Pascale National Cancer InstituteNaples, Italy
| | - Sergio Setola
- Department of Radiology, G. Pascale National Cancer InstituteNaples, Italy
| | - Roberta Fusco
- Department of Radiology, G. Pascale National Cancer InstituteNaples, Italy
| | - Antonella Petrillo
- Department of Radiology, G. Pascale National Cancer InstituteNaples, Italy
| | - Raffaele Orlando
- Department of Infectious Disease, University of Naples Federico IINaples, Italy
| | - Grazia Tosone
- Department of Infectious Disease, University of Naples Federico IINaples, Italy
| | - Fabrizio Scordino
- Department of Infectious Disease, University of Naples Federico IINaples, Italy
| | - Steven A Curley
- Department of Surgical Oncology, University of Texas MD Anderson Cancer CenterHouston, TX, USA
| |
Collapse
|
|
34
|
Kee KM, Wang JH, Lin CY, Wang CC, Cheng YF, Lu SN. Validation of the 7th edition TNM staging system for hepatocellular carcinoma: an analysis of 8,828 patients in a single medical center. Dig Dis Sci 2013; 58:2721-8. [PMID: 23703450 DOI: 10.1007/s10620-013-2716-8] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2012] [Accepted: 05/08/2013] [Indexed: 12/15/2022]
Abstract
BACKGROUND Major modification of the 7th tumor-node-metastasis (TNM) staging system for hepatocellular carcinoma (HCC) was divided into 6th stage IIIA to 7th IIIA (multiple tumors, any>5 cm) and IIIB (tumors involving a major vessel). This study aimed to validate 6th and 7th TNM systems in prognostic prediction, then analyze the impact of time, Child-Pugh classification and treatment modalities in survival. METHODS A total of 5,611 and 3,217 HCC patients were enrolled between 1986-2002 (past period) and 2003-2010 (recent period), respectively. The Akaike information criteria (AIC) within a Cox proportional hazard regression model were used to demonstrate the discriminatory ability for staging systems. RESULTS The 1-, 3-, and 5-year survival rates of past and recent periods were 44.8, 24.9, 17.1%, and 65.5, 44.5, 34.6%, respectively (p<0.001). Rates of smaller HCC detection and received curative treatment were significantly higher in the recent period than in the past period (p<0.001). Survival rates were different in each Child-Pugh class (all p<0.001). Patients receiving curative treatment had highest survival rates, followed by non-curative treatment, and untreated patients (p<0.05). In both periods, significant differences in survival curves existed between each of the stages in the 6th and 7th TNM staging (all p<0.05), and also between IIIA and IIIB in the 7th TNM (p<0.001). The AIC of two periods in the 6th and 7th TNM systems were decreased, with 77,895 and 77,630, and 19,162 and 19,135, respectively. CONCLUSION The 7th TNM provided better prognostic prediction than the 6th TNM after dividing into IIIA and IIIB. Survival rates of HCC have been improving in recent decades.
Collapse
Affiliation(s)
- Kwong-Ming Kee
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Ta Pei Road, Niao Sung District, Kaohsiung, 833, Taiwan
| | | | | | | | | | | |
Collapse
|
|
35
|
Tseng CH. Type 2 diabetes, smoking, insulin use, and mortality from hepatocellular carcinoma: a 12-year follow-up of a national cohort in Taiwan. Hepatol Int 2013; 7:693-702. [PMID: 26201803 DOI: 10.1007/s12072-012-9405-0] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2012] [Accepted: 09/18/2012] [Indexed: 02/07/2023]
Abstract
BACKGROUND The effect of smoking and insulin use in the association between diabetes and hepatocellular carcinoma (HCC) is not known. MATERIALS AND METHODS Age-standardized HCC mortality trends during 1995-2006 in the general population were calculated. A total of 88,694 type 2 diabetic patients aged ≥25 years recruited in 1995-1998 were followed till 2006. Age- and sex-specific mortality rates and the mortality rate ratios (vs. the average mortality rates in the general population) were calculated. Risk factors were evaluated by Cox regression. RESULTS The age-standardized mortality trend slightly increased significantly in women but was steady in men. For diabetic patients aged ≥25 years, 830 men and 515 women died of HCC during 1995-2006. Mortality rate ratios (95 % confidence interval) were larger with the decreasing age: 7.36 (6.52, 8.31), 2.48 (2.22, 2.78), 1.79 (1.59, 2.02), and 1.87 (1.51, 2.32) for age 25-54, 55-64, 65-74, and ≥75 years for men, respectively, 10.12 (7.73, 13.25), 4.08 (3.57, 4.67), 2.45 (2.15, 2.78), and 1.71 (1.34, 2.19) for women. Age, male sex, lower BMI, smoking, and insulin use were associated with HCC mortality, but diabetes duration was not. Smoking and insulin use carried a significantly higher risk of 22-29 % and 37-58 %, respectively, without interaction. A dose-responsive pattern between the duration of insulin use and HCC mortality was noted, with a relative risk of 1.5-1.7 in those who used insulin for ≥10 years. CONCLUSIONS Diabetic patients have a higher risk of HCC mortality, which is more remarkable in the younger age. Smoking and insulin are potentially modifiable risk factors.
Collapse
Affiliation(s)
- Chin-Hsiao Tseng
- Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
- Department of Internal Medicine, National Taiwan University Hospital, No. 7 Chung-Shan South Road, Taipei, Taiwan.
| |
Collapse
|
|
36
|
Surgical resection improves the survival of selected hepatocellular carcinoma patients in Barcelona clinic liver cancer stage C. Dig Liver Dis 2013; 45:510-5. [PMID: 23218990 DOI: 10.1016/j.dld.2012.10.019] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2012] [Revised: 10/17/2012] [Accepted: 10/28/2012] [Indexed: 02/08/2023]
Abstract
BACKGROUND Sorafenib is the only approved agent recommended by the American Association Study of Liver Disease guidelines for hepatocellular carcinoma patients in Barcelona Clinic Liver Cancer stage C. AIMS To calculate and compare overall survival rates in hepatocellular carcinoma patients in Barcelona Clinic Liver Cancer stage C treated with various therapies or supportive care alone. METHODS This was a retrospective study, in which medical data from 411 newly diagnosed hepatocellular carcinoma patients in Barcelona Clinic Liver Cancer stage C and Child-Pugh class A were analyzed and compared. RESULTS Eighty-eight patients were treated with supportive care and 323 were treated with surgical resection (68/323, 21.1%), local ablation therapy (8/323, 2.5%), transarterial embolization (140/323, 43.3%), systemic chemotherapy or radiotherapy (96/323, 29.7%), and sorafenib (11/323, 3.4%). Median survival was 11 months (95% confidence interval, 9.0-13.1) in treated patients compared with 3.9 months in the supportive care group (hazard ratio, 0.45; 95% confidence interval, 0.35-0.59; p<0.001). Patients who underwent surgical resection had the longest survival compared to patients undergoing other treatments (33.4 months versus 8.1 months, p<0.001). CONCLUSIONS Surgical resection resulted in excellent outcomes. Although sorafenib is currently recommended, oncologists should endeavour to select optimal candidates for surgical resection to gain more survival benefit.
Collapse
|
|
37
|
Zhou J, Yan T, Bi X, Zhao H, Huang Z, Zhang Y, Li Y, Feng L, Wang J, Cai J. Evaluation of seven different staging systems for alpha-fetoprotein expression in hepatocellular carcinoma after hepatectomy. Tumour Biol 2013; 34:1061-70. [PMID: 23322323 DOI: 10.1007/s13277-013-0646-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2012] [Accepted: 01/02/2013] [Indexed: 01/11/2023] Open
Abstract
Alpha-fetoprotein (AFP) represents the most important biomarker for hepatocellular carcinoma (HCC). The aim of this study was to identify the optimal staging system to predict the survival of AFP-negative and AFP-positive patients. This study analyzed the data of 431 AFP-negative HCC patients who had previously undergone surgery and 471 AFP-positive HCC candidates. Kaplan-Meier (K-M) survival estimates were plotted, and the P values were assessed using log-rank tests. The Akaike information criterion (AIC) was calculated using the results of a Cox's regression to compare the overall assessment of the seven different staging systems. The AFP-positive group displayed characteristics of poor tumor biological behavior (tumor multiplicity [P = 0.032], low grade differentiation [P = 0.000] and carcinoma cell embolus [P = 0.031]), poor liver function (Child-Pugh B classification [P = 0.003], abnormal prothrombin time activity [P = 0.037] and moderate/severe cirrhosis [P = 0.000]) and increased operative difficulties (transfusion; P = 0.001). TNM7th staging showed the lowest AIC value (1,279.528) for the AFP-negative group, while the Barcelona Clinic Liver Cancer (BCLC) staging system revealed the lowest AIC value (1,991.233) for the AFP-positive group. In conclusion, among the seven favorable staging systems, BCLC staging was superior for the AFP-positive group, while the TNM7th was a more appropriate staging model for the AFP-negative group.
Collapse
Affiliation(s)
- Jianguo Zhou
- Department of Abdominal Surgery, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100021, China
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
38
|
Muszbek N, Kreif N, Valderrama A, Benedict A, Ishak J, Ross P. Modelling survival in hepatocellular carcinoma. Curr Med Res Opin 2012; 28:1141-53. [PMID: 22563794 DOI: 10.1185/03007995.2012.691422] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
OBJECTIVES To identify the pattern of the risk of death over long-term in unresectable hepatocellular carcinoma by determining the appropriate distribution to extrapolate overall survival and to assess the role of the Weibull distribution as the standard survival model in oncology. RESEARCH DESIGN AND METHODS To select the appropriate distribution, three types of data sources have been analysed. Patient level data from two randomized controlled trials and published Kaplan-Meier curves from a systematic literature review provided short term follow-up data. They were supplemented with patient level data, with long-term follow-up from the Cancer Institute New South Wales, Australia. Published Kaplan-Meier curves were read in and a time-to-event dataset was created. Distributions were fitted to the data from the different sources separately. Their fit was assessed visually and compared using statistical criteria based on log-likelihood, the Akaike information criterion (AIC), and the Bayesian information criterion (BIC). RESULTS Based on both published and patient-level, and both short- and long-term follow-up data, the Weibull distribution, used very often in cost-effectiveness models in oncology, does not seem to offer a good fit in hepatocellular carcinoma among the different survival models. The best fitting distribution appears to be the lognormal, with loglogistic as the second-best fitting function. Results were consistent between the different sources of data. CONCLUSIONS In unresectable hepatocellular carcinoma, the Weibull model, which is often treated at the gold standard, does not appear to be appropriate based on different sources of data (two clinical trials, a retrospective database and published Kaplan-Meier curves). Lognormal distribution seems to be the most appropriate distribution for extrapolating overall survival.
Collapse
|
|
39
|
Raoul JL, Bruix J, Greten TF, Sherman M, Mazzaferro V, Hilgard P, Scherubl H, Scheulen ME, Germanidis G, Dominguez S, Ricci S, Nadel A, Moscovici M, Voliotis D, Llovet JM. Relationship between baseline hepatic status and outcome, and effect of sorafenib on liver function: SHARP trial subanalyses. J Hepatol 2012; 56:1080-1088. [PMID: 22245896 DOI: 10.1016/j.jhep.2011.12.009] [Citation(s) in RCA: 96] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2011] [Revised: 12/06/2011] [Accepted: 12/12/2011] [Indexed: 12/14/2022]
Abstract
BACKGROUND & AIMS Hepatic markers are utilized in many classification systems of patients with hepatocellular carcinoma and, by measuring organ damage and tumor stage, can influence treatment. Moreover, elevated serum concentrations of aminotransferases and alpha-fetoprotein are indicators of poor prognosis in patients with hepatocellular carcinoma. We examined the effects of sorafenib on hepatic markers by performing exploratory subset analyses of the Sorafenib HCC Assessment Randomized Protocol (SHARP) trial in patients categorized by baseline concentrations of alanine aminotransferase/aspartate aminotransferase, alpha-fetoprotein, and bilirubin; and by evaluating the effects of sorafenib on bilirubin concentrations during treatment. METHODS Patients (n=602) were grouped by baseline concentrations of alanine aminotransferase/aspartate aminotransferase (not significantly elevated, mildly elevated, or moderately elevated), alpha-fetoprotein (normal or elevated), and bilirubin (normal or elevated). Bilirubin was measured at baseline and on day 1 of each cycle. RESULTS Patients with elevated baseline concentrations of alanine aminotransferase/aspartate aminotransferase, alpha-fetoprotein, or bilirubin had shorter overall survival (OS) than those with normal baseline concentrations, irrespective of treatment group. No notable differences in safety profiles were observed between patients with normal vs. elevated alanine aminotransferase/aspartate aminotransferase, alpha-fetoprotein, or bilirubin. Median changes from baseline in bilirubin concentration at the last cycle of treatment were +0.17 and +0.19 mg/dl in the sorafenib and placebo groups, respectively. CONCLUSIONS These subset analyses suggest that sorafenib is safe and effective for hepatocellular carcinoma, irrespective of baseline alanine aminotransferase/aspartate aminotransferase, alpha-fetoprotein, or bilirubin concentration and that hepatic function remains stable over the course of sorafenib therapy.
Collapse
Affiliation(s)
- Jean-Luc Raoul
- Institut Paoli-Calmettes, Marseille, France; Institut National de la Santé et de la Recherche Médicale (INSERM) U991, Rennes, France.
| | - Jordi Bruix
- Barcelona Clínic Liver Cancer (BCLC) Group, Liver Unit, CIBERehd, Institut d'Investigacions Biomèdiques, August Pi i Sunyer (IDIBAPS), Hospital Clínic Barcelona, Barcelona, Spain
| | - Tim F Greten
- Medizinische Hochschule Hannover, Abteilung fur Gastroenterologie, Hepatologie und Endokrinologie, Hannover, Germany
| | | | - Vincenzo Mazzaferro
- National Cancer Institute, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Foundation, Milan, Italy
| | | | - Hans Scherubl
- Medizinische Klinik "Charite", Campus Benjamin Franklin, Berlin, Germany
| | - Max E Scheulen
- Innere Klinik (Tumorforschung), West German Cancer Center, Universitätsklinikum Essen, Essen, Germany
| | - Georgios Germanidis
- AHEPA University Hospital, First Department of Medicine, Thessaloniki, Greece
| | - Sophie Dominguez
- Centre Oscar Lambret, Departement de Cancerologie Digestive et Urologique, Lille, France
| | | | - Andrea Nadel
- Bayer HealthCare Pharmaceuticals, Montville, NJ, USA
| | | | | | - Josep M Llovet
- Barcelona Clínic Liver Cancer (BCLC) Group, Liver Unit, CIBERehd, Institut d'Investigacions Biomèdiques, August Pi i Sunyer (IDIBAPS), Hospital Clínic Barcelona, Barcelona, Spain; Mount Sinai Liver Cancer Program, Mount Sinai School of Medicine, New York, NY, USA; Institució Catalana de Recerca I Estudis Avançats, Catalonia, Spain
| |
Collapse
|
|
40
|
Gish RG, Lencioni R, Di Bisceglie AM, Raoul JL, Mazzaferro V. Role of the multidisciplinary team in the diagnosis and treatment of hepatocellular carcinoma. Expert Rev Gastroenterol Hepatol 2012; 6:173-85. [PMID: 22375523 DOI: 10.1586/egh.11.105] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
It has long been appreciated that hepatocellular carcinoma (HCC) is a complex disease. HCC is typically preceded by liver cirrhosis, which is itself caused by various types of hepatitis of both viral and nonviral etiologies. Thus, the treatment of patients with HCC requires multiple healthcare professionals, including hepatologists, medical oncologists, surgical oncologists, transplantation surgeons, diagnostic radiologists, pathologists, nurses, nurse practitioners and interventional radiologists. These specialists should meet regularly to review patients' progress, ensure that treatments are individualized for each patient and agree on next steps. We review case presentations provided by the authors to illustrate the benefits and advantages of the multidisciplinary team matrix in the management of patients with HCC, including the effects of this treatment technique on patient outcome, survival and quality of life.
Collapse
Affiliation(s)
- Robert G Gish
- Center for Hepatobiliary Disease, University of California, San Diego, 200 West Arbor Drive, San Diego, CA 92103-8413, USA.
| | | | | | | | | |
Collapse
|
|
41
|
He J, Zeng ZC, Fan J, Zhou J, Sun J, Chen B, Yang P, Wang BL, Zhang BH, Zhang JY. Clinical features and prognostic factors in patients with bone metastases from hepatocellular carcinoma after liver transplantation. BMC Cancer 2011; 11:492. [PMID: 22107882 PMCID: PMC3298548 DOI: 10.1186/1471-2407-11-492] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2011] [Accepted: 11/22/2011] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Little is known about the clinical features and prognostic factors of bone metastases of hepatocellular carcinoma (HCC) following liver transplantation (LT). METHODS All adult patients undergoing LT from 2001 to 2010 were reviewed. Patients with HCC bone metastases after LT received external beam radiotherapy(EBRT) during this period. Demographic variables, laboratory values, and tumor characteristics were determined before LT and EBRT. Total radiation dose ranged from 8 to 60 Gy(median dose 40.0 Gy). RESULTS The trunk was the most common site of bone metastases with finding of expansile soft-tissue masses in 23.3% of patients. Overall pain relief from EBRT occurred in 96.7% (29/30). No consistent dose-response relationship was found for palliation of with doses between 30 and 56 Gy (P = 0.670). The median survivals from the time of bone metastases was 8.6 months. On univariate and multivariate analyses, better survival was significantly associated with a better Karnofsky performance status (KPS) and well-controlled intrahepatic tumor, but not with lower alpha-fetoprotein levels. The median time from LT to bone metastases was 7.1 months. Patients exceeding the Shanghai criteria presented with bone metastases earlier than those within the Fudan criteria. Patients with soft-tissue extension always had later bone metastases. The majority of deaths were caused by liver failure due to hepatic decompensation or tumor progression. CONCLUSION The prognostic factors of bone metastases of HCC following LT are KPS and well-controlled intrahepatic. Even though survival is shorter for these patients, EBRT provides effective palliation of pain.
Collapse
Affiliation(s)
- Jian He
- Department of Radiation Oncology, Fudan University, Shanghai, China
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
42
|
Pinter M, Sieghart W, Hucke F, Graziadei I, Vogel W, Maieron A, Königsberg R, Weissmann A, Kornek G, Matejka J, Stauber R, Buder R, Grünberger B, Schöniger-Hekele M, Müller C, Peck-Radosavljevic M. Prognostic factors in patients with advanced hepatocellular carcinoma treated with sorafenib. Aliment Pharmacol Ther 2011; 34:949-59. [PMID: 21883324 DOI: 10.1111/j.1365-2036.2011.04823.x] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
BACKGROUND Sorafenib is the new reference standard for patients with advanced hepatocellular carcinoma (HCC). AIM To identify prognostic factors in sorafenib-treated HCC patients and to evaluate outcomes with respect to liver function. METHODS In this retrospective study, 148 HCC patients received sorafenib 400 mg b.d. across 11 Austrian institutions. Seventy-eight HCC patients who received best supportive care (BSC) in the pre-sorafenib era served as a control. RESULTS In sorafenib-treated patients, low baseline α-fetoprotein, low Child-Pugh (CP) score, compensated cirrhosis, and low baseline aspartate aminotransferase (AST) were associated with significantly longer overall survival (OS) on univariate analysis. CP score and baseline AST remained independent prognostic factors on multivariate analysis. In patients with Barcelona Clinic liver Cancer (BCLC) stage B or C HCC (sorafenib: n = 139; BSC: n = 39), CP-A patients had a median OS of 11.3 (sorafenib [n = 76]) vs. 6.4 (BSC [n = 17]) months (P = 0.010), and CP-B patients had a median OS of 5.5 (sorafenib [n = 55]) vs. 1.9 (BSC [n = 22]) months (P = 0.021). In the sorafenib group, median OS according to baseline AST was 11.8 (<100 U/L [n = 58]) vs. 3.9 (≥100 U/L [n = 15]) months for CP-A patients (P = 0.127), and 6.5 (<100 U/L [n = 33]) vs. 2.1 (≥100 U/L [n = 21]) months for CP-B patients (P = 0.011). There was no survival difference between sorafenib and BSC in patients with BCLC stage D HCC (1.5 vs. 1.4 months; P = 0.116). CONCLUSIONS Sorafenib was associated with improved survival in both CP-A and CP-B patients. In CP-B patients, baseline AST may be helpful in determining which patients are most likely to benefit from sorafenib.
Collapse
Affiliation(s)
- M Pinter
- Department of Gastroenterology and Hepatology, AKH & Medizinische Universität Wien, Austria
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
43
|
Yu MC, Chan KM, Lee CF, Lee YS, Eldeen FZ, Chou HS, Lee WC, Chen MF. Alkaline phosphatase: does it have a role in predicting hepatocellular carcinoma recurrence? J Gastrointest Surg 2011; 15:1440-1449. [PMID: 21541770 DOI: 10.1007/s11605-011-1537-3] [Citation(s) in RCA: 79] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2010] [Accepted: 04/04/2011] [Indexed: 01/31/2023]
Abstract
BACKGROUNDS Surgical resection remains the first line of treatment for earlier stages of hepatocellular carcinoma (HCC), and it offers the best prognosis for long-term survival. Nevertheless, the recurrence rates after resection are still high in reports. Therefore, it is still essential to explore any potential prognostic factors to attain relatively longer-term survival of HCC patients. MATERIALS AND METHODS In the period from 1983 to 2005, 1,685 patients who underwent hepatectomy at Chang Gung Memorial hospital were enrolled in the study, and their clinicopathological data were retrospectively reviewed for survival analysis. RESULTS The 1-, 3-, 5-, and 10-year disease-free survival (DFS) rates in this series were 60.3%, 39.7%, 31.3%, and 24.0%, respectively, whereas the 1-, 3-, 5-, and 10-year overall survival (OS) rates were 80.1%, 59.1%, 46.6%, and 27.7%, respectively. Gross vascular invasion, tumor status, lymph node involvement, satellite lesion, positive surgical margin, alkaline phosphatase (ALP), albumin, presence of cirrhosis, and Child grade B or C were independent prognostic factors for prediction of DFS; while α-fetoprotein, ALP, surgical factors, including complications, blood transfusion, positive resection margin, and tumor characters including tumor status, vascular invasion, and lack of tumor encapsulation were found to be independent predicting factors for OS, as determined by Cox regression analysis. Interestingly, we found that preoperative level of ALP was one of the most important independent predictors of recurrence, even more important that α-fetoprotein (AFP) as we noticed that elevation of ALP above (82 U/L) predicted poor prognosis in patients where AFP levels was less than 66 ng/ml. It is worth to mention that ALP was statistically related to other liver function tests, but not tumor characters by hierarchical clustering; which means that we were able to correlate ALP with prognosis statistically, but not with pathological criteria of the tumor; to elucidate these finding, further basic science research is required. CONCLUSION ALP among liver function tests, in addition to other tumor characters were independent factors for DFS and OS; our results suggest that preoperative ALP levels could be utilized to monitor and predict recurrence in high risk HCC patients.
Collapse
Affiliation(s)
- Ming-Chin Yu
- Department of Surgery, Chang Gung Memorial Hospital, Kuei Shan Hsiang, Taoyuan county, Taiwan
| | | | | | | | | | | | | | | |
Collapse
|
|
44
|
Lee CW, Chan KM, Lee CF, Yu MC, Lee WC, Wu TJ, Chen MF. Hepatic resection for hepatocellular carcinoma with lymph node metastasis: clinicopathological analysis and survival outcome. Asian J Surg 2011; 34:53-62. [PMID: 21723467 DOI: 10.1016/s1015-9584(11)60020-1] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2010] [Revised: 12/13/2010] [Accepted: 04/14/2011] [Indexed: 01/29/2023] Open
Abstract
OBJECTIVE Lymph node metastasis (LNM) rarely occurs in hepatocellular carcinoma (HCC). Few studies have reported the potential risk factors of LNM and the influence of LNM on the progression and prognosis of HCC. The purposes of this study were to explore the clinicopathological characteristics of operable HCC with LNM and to demonstrate the effects of LNM on HCC prognosis. METHODS A retrospective review of 2,034 HCC patients undergoing surgery from 1982 to 2005 was performed. The influence of LNM was assessed by clinicopathological factors, tumour recurrence, and overall survival. A total of 66 randomly selected patients matched for clinicopathological variables were used to analyse the difference in survival. RESULTS A total of 25 patients (1.23%) were reported to have LNM. Higher preoperative carcinoembryonic antigen levels (> 10 ng/mL) were significantly associated with a higher incidence of LNM than were low preoperative carcinoembryonic antigen levels (≤ = 10 ng/mL) (15.38%vs. 3.79%, p = 0.042). Furthermore, HCC with LNM (N1 disease) was larger in size (mean, 9.44 vs. 5.85 cm, p = 0.016) and significantly associated with vascular invasion, worse histological grade, and nonencapsulation (p = 0.002, < 0.001, and < 0.001, respectively). Finally, patients with HCC accompanied by LNM had shorter mean disease-free survival and overall survival (p = 0.001 and < 0.001, respectively). CONCLUSION This study identified the worst prognosis of HCC in a population with LNM. HCC with LNM tends to be the infiltrating type with larger tumour size (> 5 cm), presence of microvascular invasion, and worse histological grade. Liver resection with lymphadenectomy is possibly beneficial for patients with HCC accompanied by LNM.
Collapse
Affiliation(s)
- Chao-Wei Lee
- Department of Surgery, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan
| | | | | | | | | | | | | |
Collapse
|
|
45
|
Kao CC, Chen MK, Kuo WH, Chen TY, Su SC, Hsieh YH, Liu CL, Chou MC, Tsai HT, Yang SF. Influence of glutathione-S-transferase theta (GSTT1) and micro (GSTM1) gene polymorphisms on the susceptibility of hepatocellular carcinoma in Taiwan. J Surg Oncol 2010; 102:301-7. [PMID: 20672314 DOI: 10.1002/jso.21643] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
BACKGROUND AND OBJECTIVES Hepatocellular carcinoma (HCC) is one of the most frequent malignant neoplasms worldwide and is the second leading cause of cancer death in Taiwan. Genetic polymorphism has been reported as a factor for increased susceptibility of HCC. Glutathione-S-transferases theta (GSTT1) and micro (GSTM1) play essential roles in detoxification of ingested xenobiotics and modulation of the susceptibility of gene-related cancer. The aim of this study was to estimate the relationships between these two gene polymorphisms and HCC risk and clinicopathological status in Taiwanese. METHODS Polymerase chain reaction (PCR) was used to determine gene polymorphisms of 102 patients with HCC and 386 healthy controls. RESULTS Both gene polymorphisms were not associated with the clinical pathological status of HCC and serum levels of liver-related clinical pathological markers. While no relationship between GSTM1 gene polymorphism and HCC susceptibility was found, individuals of age <56 years old with GSTT1 present genotype have a risk of 2.77-fold (95% CI: 1.09-7.09) for HCC compared to that with null variant, after adjustment for other confounders. CONCLUSIONS GSTT1 and GSTM1 null genotypes do not associate with increased risk of HCC.
Collapse
Affiliation(s)
- Chia-Chun Kao
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
46
|
Wang W, Feng X, Zhang T, Jin J, Wang S, Liu Y, Song Y, Liu X, Yu Z, Li Y. Prospective evaluation of microscopic extension using whole-mount preparation in patients with hepatocellular carcinoma: Definition of clinical target volume for radiotherapy. Radiat Oncol 2010; 5:73. [PMID: 20731853 PMCID: PMC2936917 DOI: 10.1186/1748-717x-5-73] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2010] [Accepted: 08/23/2010] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND To define the clinical target volume (CTV) for radiotherapy in patients with hepatocellular carcinoma (HCC). METHODS A prospective study was conducted to histologically evaluate the presence and the distance of microscopic extension (ME) for resected HCC on the basis of examination of whole-mount preparations of carcinoma tissue sections. RESULTS A total of 380 whole-mount slides prepared from tumor samples of 76 patients with HCC were examined. Patients with elevated pretreatment AFP levels exhibited higher risk of ME as compared to those with normal pretreatment AFP levels (93.9% vs. 69.8%, P < 0.01). ME positivity was 16.7% for Grade 1, 79.1% for Grade 2, and 96.3% for Grade 3 tumors (P < 0.01). The mean distance of ME was 0.0 ± 0.1 mm (range 0-0.2 mm) for Grade 1, 0.9 ± 0.9 mm (range 0-4.5 mm) for Grade 2, and 1.9 ± 1.9 mm (range 0-8.0 mm) for Grade 3 tumors (P < 0.01). CONCLUSIONS The CTV margins for tumor Grades 1, 2, and 3 HCC, are recommended to be 0.2 mm, 4.5 mm, and 8.0 mm beyond the gross tumor margin, respectively, to account for possible ME of the tumors in all patients.
Collapse
Affiliation(s)
- Weihu Wang
- Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, PR China
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
47
|
Ikeda M, Maeda S, Ashihara H, Nagahama H, Tanaka M, Sasaki Y. Transcatheter arterial infusion chemotherapy with cisplatin-lipiodol suspension in patients with hepatocellular carcinoma. J Gastroenterol 2010; 45:60-7. [PMID: 19655081 DOI: 10.1007/s00535-009-0109-8] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2008] [Accepted: 07/12/2009] [Indexed: 02/04/2023]
Abstract
PURPOSE The aim of this study was to investigate the antitumor efficacy of treatment, identify prognostic factors, and construct a prognostic index in patients with hepatocellular carcinoma treated by transcatheter arterial infusion chemotherapy (TAI) using cisplatin suspended in lipiodol. METHODS We analyzed the outcomes in a total of 94 consecutive patients with previously untreated hepatocellular carcinoma who were treated by TAI using cisplatin suspended in lipiodol. RESULTS Twenty-seven patients (29%) showed complete response and 21 patients (22%) showed partial response, with an overall response rate of 51% (95% confidence interval, 41-61%). The median survival time was 2.5 years and the proportions of survivors at 1, 2, and 5 years were 81.6, 65.2, and 18.3%, respectively. The results of multivariate analysis indicated a significant association of serum albumin > or =3.0 g/dL, maximum tumor size < or =3.0 cm, absence of ascites, and unilateral distribution of the tumors with a favorable survival. For clinical application, we also propose a prognostic index based on a combination of these prognostic factors. Based on this index, the patients were classified into three groups: those with good, intermediate, and poor prognosis. The median survival times in these three groups were 4.3, 2.7, and 1.1 years, respectively (p < 0.01). CONCLUSIONS TAI with cisplatin suspended in lipiodol exhibited favorable tumor efficacy and survival in patients with hepatocellular carcinoma. The prognostic factors identified and the index proposed based on these factors may be useful for predicting life expectancy, determining treatment strategies, and designing future clinical trials.
Collapse
Affiliation(s)
- Masafumi Ikeda
- Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1, Honjo, Kumamoto 860-8556, Japan
| | | | | | | | | | | |
Collapse
|
|
48
|
Weng CJ, Hsieh YH, Tsai CM, Chu YH, Ueng KC, Liu YF, Yeh YH, Su SC, Chen YC, Chen MK, Yang SF. Relationship of insulin-like growth factors system gene polymorphisms with the susceptibility and pathological development of hepatocellular carcinoma. Ann Surg Oncol 2010; 17:1808-15. [PMID: 20119675 DOI: 10.1245/s10434-009-0904-8] [Citation(s) in RCA: 58] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2009] [Indexed: 12/16/2022]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is one of the major causes of cancer-related death worldwide. The insulin-like growth factors (IGFs) system consists of a group of proteins which may induce cell proliferation and inhibit cell apoptosis through several signal pathways, leading to transformation of normal cells into cancer cells. However, the impact of genetic polymorphisms of the IGFs system on HCC has not been clarified. METHODS In this case-control study, a total of 102 HCC patients and 306 age- and gender-matched controls were recruited. The genetic polymorphisms of the IGFs system genes, including IGF-1, IGF-2, IGF-1receptor (IGF-1R), IGF-2R, IGF binding protein (IGFBP-3), and insulin (INS) genes, were analyzed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and real-time PCR genotyping analysis. RESULTS A significant difference (p = 0.02) between case and control group in the distribution frequency of IGF-2 +3580 polymorphism was observed. Multiple regression model analysis showed that the presence of AA or AG at IGF-2R may exhibit a potential protective effect against hepatitis C [odds ratio (OR) = 0.35, 95% confidence interval (CI) = 0.15-0.82]. The combination of IGF-2 +3580 AA genotype and IGF-2R GG genotype may present a significantly lower risk of HCC (OR = 0.20, 95% CI = 0.05-0.87). Additionally, no polymorphisms of any IGFs system genes were associated with liver-related clinicopathological markers in serum. CONCLUSIONS Among IGFs system genes, IGF-2 and IGF-2R gene polymorphisms and combination could be considered as the most important factors contributing to increased susceptibility and pathological development of HCC.
Collapse
|
|
49
|
Kuo YH, Lu SN, Chen CL, Cheng YF, Lin CY, Hung CH, Chen CH, Changchien CS, Hsu HC, Hu TH, Lee CM, Wang JH. Hepatocellular carcinoma surveillance and appropriate treatment options improve survival for patients with liver cirrhosis. Eur J Cancer 2010; 46:744-51. [PMID: 20060710 DOI: 10.1016/j.ejca.2009.12.018] [Citation(s) in RCA: 77] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2009] [Revised: 12/10/2009] [Accepted: 12/14/2009] [Indexed: 01/12/2023]
Abstract
OBJECTIVE/AIM Hepatocellular carcinoma (HCC) surveillance is a common practice for patients with liver cirrhosis. The aims of the study were to assess impacts of surveillance and therapeutic options on survival of patients with HCC. METHODS A total of 1436 cirrhotic patients with newly diagnosed HCC were enrolled between January 2002 and December 2004. Patients with HCC detected within periodic surveillance were the surveillance group (n=318, 22.1%). The other patients with HCC incidentally detected were the non-surveillance group (n=1118, 77.95%). Initial treatment options were recorded and overall survival was analysed. RESULTS Compared with patients in the non-surveillance group, larger proportions of patients in the surveillance group possessed small tumours, at an early stage without vascular invasion or metastases, and afforded more curative treatment options including surgical resection, radiofrequency ablation and percutaneous ethanol injection. The overall survival was better for patients in surveillance (3-year survival rate: 59.1% versus 29.3%, p<0.001), early stages by Barcelona Clinic Liver Cancer (BCLC) staging or curative treatment options. Multivariate analysis demonstrated surveillance, hepatitis aetiology, alpha-fetoprotein, tumour gross type, tumour stage and treatment options were associated factors for patients' survival. Moreover, surveillance patients in curative BCLC stage following the treatment guideline for HCC proposed by the American association for the study of liver disease (AASLD) had a significantly better 3-year survival rate (77.1% versus 55.2%, p<0.001). CONCLUSIONS HCC surveillance for cirrhotic patients could detect HCC at early and curative stages. However, appropriate treatment options following AASLD guideline further improve the survival for patients in early stage.
Collapse
Affiliation(s)
- Yuan-Hung Kuo
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, 123 Ta-Pei Rd., Niao-Sung, Kaohsiung County 819, Taiwan
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
50
|
Chan SL, Chan ATC, Yeo W. Role of alpha-fetoprotein in hepatocellular carcinoma: prognostication, treatment monitoring or both? Future Oncol 2009; 5:889-899. [PMID: 19663737 DOI: 10.2217/fon.09.64] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
Despite recent breakthroughs in the treatment for both early and advanced hepatocellular carcinoma, the development of markers for prognostication and treatment monitoring remains to be explored. Serum alpha-fetoprotein has been frequently measured at diagnosis and serially during treatment by clinicians for decades, with an aim for prognostication of disease and monitoring of treatment response. In this review, the evidence regarding the prognostic value of serum alpha-fetoprotein and the value of serial alpha-fetoprotein in the monitoring of treatment efficacy will be discussed, with emphasis on recent data.
Collapse
Affiliation(s)
- Stephen L Chan
- Department of Clinical Oncology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China
| | | | | |
Collapse
|