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1
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Jo HS, Park PJ, Yu YD, Choi YJ, Yu SH, Kim DS. Clinical significance of surgical resection for hepatocellular carcinoma with portal vein invasion: a nationwide cohort study. Hepatobiliary Surg Nutr 2024; 13:814-823. [PMID: 39507744 PMCID: PMC11534781 DOI: 10.21037/hbsn-23-578] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2023] [Accepted: 03/15/2024] [Indexed: 11/08/2024]
Abstract
Background Hepatocellular carcinoma (HCC) with portal vein invasion (PVI) is considered an advanced stage with a poor prognosis. Although current guidelines recommend systemic treatment for HCC with PVI, surgical resection could produce acceptable outcomes in selected patients. This study aimed to identify the clinical significance of surgical resection for HCC with PVI patients using a large-scale nationwide registry. Methods This retrospective, multicenter, observational cohort analyzed data from the Korean Primary Liver Cancer Registry. A total of 16,781 patients who were newly diagnosed with HCC between 2008 and 2018 were enrolled in this study. Patients with worse Child-Turcotte-Pugh scores (≥7) or performance status (≥2) were excluded. Among them, 998 patients who received treatment for HCC with PVI were included in the analysis and were divided into two groups: resection group of 151 (15.1%) and palliative group of 847 (84.9%) who received transarterial and systemic therapy according to the treatment intent. After matching the number and size of the tumors and model for end-stage liver disease (MELD) score between the groups, the final study cohort for analysis comprised 151 (26.6%) patients in the resection group and 417 (73.4%) in the palliative group. The primary endpoints were overall survival (OS) and cancer-specific survival (CSS). Results The number and maximum size of HCC did not differ between the resection and palliative groups after matching [1 (range, 1-5) vs. 1 (range, 1-6), P=0.11 and 5.5 (range, 1.2-20.6) vs. 6.0 (range, 1.0-20.5) cm, P=0.24, respectively]. Tumor markers, including alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II), also did not differ between the groups (P=0.29 and P=0.36, respectively). The 5-year OS and CSS rates of the resection and palliative groups were 44.8% and 17.4% (P<0.001) and 47.7% and 18.6% (P<0.001), respectively. Multivariate analysis showed that palliative treatment intent was the most significant risk factor for OS and CSS [odds ratio (OR) =2.24; 95% confidence interval (CI): 1.66-3.02; P<0.001 and OR =2.29; 95% CI: 1.68-3.12; P<0.001, respectively]. Conclusions Surgical resection could significantly improve OS and CSS in selected HCC with PVI patients who have preserved liver function and performance status.
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Affiliation(s)
- Hye-Sung Jo
- Division of HBP Surgery and Liver Transplantation, Department of Surgery, Korea University College of Medicine, Seoul, Republic of Korea
| | - Pyoung-Jae Park
- Division of Transplantation and Vascular Surgery, Department of Surgery, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea
| | - Young-Dong Yu
- Division of HBP Surgery and Liver Transplantation, Department of Surgery, Korea University College of Medicine, Seoul, Republic of Korea
| | - Yoo Jin Choi
- Division of HBP Surgery and Liver Transplantation, Department of Surgery, Korea University College of Medicine, Seoul, Republic of Korea
| | - Se Hyeon Yu
- Division of HBP Surgery and Liver Transplantation, Department of Surgery, Korea University College of Medicine, Seoul, Republic of Korea
| | - Dong-Sik Kim
- Division of HBP Surgery and Liver Transplantation, Department of Surgery, Korea University College of Medicine, Seoul, Republic of Korea
| | - Korean Liver Cancer Association
- Division of HBP Surgery and Liver Transplantation, Department of Surgery, Korea University College of Medicine, Seoul, Republic of Korea
- Division of Transplantation and Vascular Surgery, Department of Surgery, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea
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Bhangui P. Liver transplantation and resection in patients with hepatocellular cancer and portal vein tumor thrombosis: Feasible and effective? Hepatobiliary Pancreat Dis Int 2024; 23:123-128. [PMID: 37880019 DOI: 10.1016/j.hbpd.2023.10.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Accepted: 09/27/2023] [Indexed: 10/27/2023]
Abstract
Patients with locally advanced hepatocellular cancer (HCC) and portal vein tumor thrombosis (PVTT) have a dismal prognosis since limited treatment options are available for them. In recent years, effective systemic therapy, and advances in the understanding of technicalities and effectiveness of ablative therapies especially radiotherapy, have given some hope to prolong survival in them. This review summarized recent evidence in literature regarding the possible role of liver resection (LR) and liver transplantation (LT) in patients with locally advanced HCC and PVTT with no extrahepatic disease. Downstaging therapies have helped make curative resection or LT a reality in selected patients. This review emphasizes on the key points to focus on when considering surgery in these patients, who are usually relegated to palliative systemic therapy alone. Meticulous patient selection based on tumor biology, documented downstaging based on imaging and decrease in tumor marker levels, and an adequate waiting period to demonstrate stable disease, may help obtain satisfactory long-term outcomes post LR or LT in an intention to treat strategy in patients with HCC and PVTT.
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Affiliation(s)
- Prashant Bhangui
- Institute of Liver Transplantation and Regenerative Medicine, Medanta - The Medicity, Sector 38, Gurgaon, Delhi NCR 122001, India.
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3
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Gyoda Y, Ichida H, Kawano F, Takeda Y, Yoshioka R, Imamura H, Mise Y, Fukumura Y, Saiura A. A patient alive without disease 32 months after conversion surgery following lenvatinib treatment for hepatocellular carcinoma with a tumor thrombus originating in the middle hepatic vein and reaching the right atrium via the suprahepatic vena cava: a case report. Clin J Gastroenterol 2024; 17:311-318. [PMID: 38277091 DOI: 10.1007/s12328-023-01909-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2023] [Accepted: 12/12/2023] [Indexed: 01/27/2024]
Abstract
Conversion surgery for initially unresectable hepatocellular carcinoma appears to be increasing in incidence since the advent of new molecular target drugs and immune checkpoint inhibitors; however, reports on long-term outcomes are limited and the prognostic relevance of this treatment strategy remains unclear. Herein, we report the case of a 75-year-old man with hepatocellular carcinoma, 108 mm in diameter, accompanied by a tumor thrombus in the middle hepatic vein that extended to the right atrium via the suprahepatic vena cava. He underwent conversion surgery after preceding lenvatinib treatment and is alive without disease 51 months after the commencement of treatment and 32 months after surgery. Just before conversion surgery, after 19 months of lenvatinib treatment, the main tumor had reduced in size to 72 mm in diameter, the tip of the tumor thrombus had receded back to the suprahepatic vena cava, and the tumor thrombus vascularity was markedly reduced. The operative procedure was an extended left hepatectomy with concomitant middle hepatic vein resection. The tumor thrombus was removed under total vascular exclusion via incision of the root of the middle hepatic vein. Histopathological examination revealed that more than half of the liver tumor and the tumor thrombus were necrotic.
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Affiliation(s)
- Yu Gyoda
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan
| | - Hirofumi Ichida
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan
| | - Fumihiro Kawano
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan
| | - Yoshinori Takeda
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan
| | - Ryuji Yoshioka
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan
| | - Hiroshi Imamura
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan
| | - Yoshihiro Mise
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan
| | - Yuki Fukumura
- Department of Human Pathology, Juntendo University School of Medicine, Tokyo, Japan
| | - Akio Saiura
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan.
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Duan X, Li H, Chen P, Sun T, Kuang D, Lu H, Qiao B, Fan Z, Ren Z, Han X. Transcatheter arterial chemoembolization using CalliSpheres beads loaded with arsenic trioxide for unresectable large or huge hepatocellular carcinoma: a prospective study. Eur Radiol 2024; 34:1258-1267. [PMID: 37581654 DOI: 10.1007/s00330-023-10097-1] [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: 11/30/2022] [Revised: 05/22/2023] [Accepted: 06/25/2023] [Indexed: 08/16/2023]
Abstract
OBJECTIVES To determine the safety and efficacy of transcatheter arterial chemoembolization with CalliSpheres® beads loaded with arsenic trioxide (CBATO-TACE) in the first-line treatment of patients with large (5 cm ≤ maximum diameter < 10 cm) or huge (maximum diameter ≥ 10 cm) hepatocellular carcinoma (HCC). METHODS Patients were randomly allocated to the CBATO-TACE group and the conventional transcatheter arterial chemoembolization (cTACE) group. The primary endpoint was progression-free survival (PFS). The secondary endpoint was overall survival (OS), treatment response, and treatment-related adverse events (TRAEs). The extrahepatic collateral arteries, liver function, and liver fibrosis after the first TACE were also evaluated. RESULTS From September 2018 to September 2020, a total of 207 patients who underwent TACE were consecutively enrolled in this study. The median PFS was 9.5 months (range: 8.0 - 11.0) in the CBATO group, which was significantly longer than that in the cTACE group (6.0 months, range: 4.0-6.0) (p < 0.0001). Patients in the CBATO group had a median OS of 22 months (range: 20.0 - 27.0) compared with 16 months (range: 15.0 - 20.0) in the cTACE group (p = 0.0084). The most common TRAEs were fever (p = 0.043), and nausea and vomiting (p = 0.002), which were more observed in the cTACE group. In addition, the progressive disease time, pulmonary metastasis rate (p = 0.01), the mean number of extrahepatic collateral arteries (p = 0.01), and average number of TACE sessions (p = 0.025) were significantly decreased in the CBATO group. CONCLUSIONS CBATO-TACE achieved better therapeutic outcomes and similar safety profile compared to cTACE in large or huge HCC patients. Furthermore, CBATO-TACE was able to reduce extrahepatic collateral arteries production and extrahepatic lung metastasis. CLINICAL RELEVANCE STATEMENT Our study showed that CalliSpheres® beads loaded with arsenic trioxide (CBATO-TACE) were effective and safe for the treatment of large and giant HCC. In addition, CBATO-TACE can reduce lateral hepatic branch artery formation and extrahepatic pulmonary metastasis, which provides a new treatment approach for unresectable HCC. KEY POINTS • We compare long-term efficacy and safety of transcatheter arterial chemoembolization with CalliSpheres® beads loaded with arsenic trioxide (CBATO-TACE) and conventional transcatheter arterial chemoembolization (cTACE) in patients with large (5 cm ≤ maximum diameter < 10 cm) or huge HCC (maximum diameter ≥ 10 cm). • Compared with cTACE, CBATO-TACE significantly improved therapeutic outcomes, overall survival, and progression-free survival in patients with large or huge HCC. The safety assessment suggested that CBATO-TACE is a safe treatment that improves the quality of life and has good treatment adherence.
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Affiliation(s)
- Xuhua Duan
- Department of Interventional Radiology, The First Affiliated Hospital, Zhengzhou University, No. 1, East Jian She Road, Zhengzhou, 450052, Henan Province, People's Republic of China
| | - Hao Li
- Department of Interventional Radiology, The First Affiliated Hospital, Zhengzhou University, No. 1, East Jian She Road, Zhengzhou, 450052, Henan Province, People's Republic of China
| | - Pengfei Chen
- Department of Interventional Radiology, The First Affiliated Hospital, Zhengzhou University, No. 1, East Jian She Road, Zhengzhou, 450052, Henan Province, People's Republic of China
| | - Tao Sun
- Department of Hepatobiliary Surgery, The First Affiliated Hospital, Zhengzhou University, No. 1, East Jian She Road, Zhengzhou, 450052, Henan Province, People's Republic of China
| | - Donglin Kuang
- Department of Interventional Radiology, The First Affiliated Hospital, Zhengzhou University, No. 1, East Jian She Road, Zhengzhou, 450052, Henan Province, People's Republic of China
| | - Huibin Lu
- Department of Interventional Radiology, The First Affiliated Hospital, Zhengzhou University, No. 1, East Jian She Road, Zhengzhou, 450052, Henan Province, People's Republic of China
| | - Bingbing Qiao
- Department of Hepatobiliary Surgery, The First Affiliated Hospital, Zhengzhou University, No. 1, East Jian She Road, Zhengzhou, 450052, Henan Province, People's Republic of China
| | - Zhengjun Fan
- Department of Hepatobiliary Surgery, The First Affiliated Hospital, Zhengzhou University, No. 1, East Jian She Road, Zhengzhou, 450052, Henan Province, People's Republic of China
| | - Zhuangjian Ren
- Department of Interventional Radiology, The First Affiliated Hospital, Zhengzhou University, No. 1, East Jian She Road, Zhengzhou, 450052, Henan Province, People's Republic of China.
| | - Xinwei Han
- Department of Interventional Radiology, The First Affiliated Hospital, Zhengzhou University, No. 1, East Jian She Road, Zhengzhou, 450052, Henan Province, People's Republic of China.
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5
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Singal AG, Kanwal F, Llovet JM. Global trends in hepatocellular carcinoma epidemiology: implications for screening, prevention and therapy. Nat Rev Clin Oncol 2023; 20:864-884. [PMID: 37884736 DOI: 10.1038/s41571-023-00825-3] [Citation(s) in RCA: 182] [Impact Index Per Article: 91.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/25/2023] [Indexed: 10/28/2023]
Abstract
Hepatocellular carcinoma (HCC) mortality rates are increasing globally, and particularly in the Western world. Cirrhosis remains the predominant risk factor for HCC. However, epidemiological shifts in the incidence of HCC from patients with virus-related liver disease to those with non-viral aetiologies, including alcohol-associated and metabolic dysfunction-associated steatotic liver disease, have important implications for prevention, surveillance and treatment. Hepatitis B vaccination and antiviral therapy for hepatitis B and C are effective for primary prevention of virus-related HCCs, but chemoprevention strategies for non-viral liver disease remain an unmet need. Emerging data suggest associations between aspirin, statins, metformin and coffee and reduced HCC incidence, although none has been proved to be causally related. Secondary prevention of HCC via semi-annual surveillance is associated with improvements in early detection and thus reduced mortality; however, current tools, including abdominal ultrasonography, have suboptimal sensitivity for the detection of early stage HCC, particularly in patients with obesity and/or non-viral liver disease. Promising blood-based or imaging-based surveillance strategies are emerging, although these approaches require further validation before adoption in clinical practice. In the interim, efforts should be focused on maximizing use of the existing surveillance tools given their prevalent underuse globally. Remarkable advances have been made in the treatment of HCC, including expanded eligibility for surgical therapies, improved patient selection for locoregional treatments and increased systemic treatment options, including immune-checkpoint inhibitors. In this Review, we discuss trends in the epidemiology of HCC and their implications for screening, prevention and therapy.
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Affiliation(s)
- Amit G Singal
- Division of Digestive and Liver Diseases, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA.
| | - Fasiha Kanwal
- Section of Gastroenterology and Hepatology and Health Services Research, Department of Medicine, Baylor College of Medicine, Houston, TX, USA
- Section of Health Services Research, Department of Medicine, Baylor College of Medicine, Houston, TX, USA
- VA Health Services Research & Development Center for Innovations in Quality, Effectiveness, and Safety (IQuESt), Houston, TX, USA
- Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA
| | - Josep M Llovet
- Mount Sinai Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Translational Research in Hepatic Oncology, Liver Unit, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clinic, University of Barcelona, Barcelona, Spain
- Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain
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6
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Bogdanovic A, Djokic Kovac J, Zdujic P, Djindjic U, Dugalic V. Liver resection versus transarterial chemoembolisation for the treatment of intermediate hepatocellular carcinoma: a systematic review and meta-analysis. Int J Surg 2023; 109:1439-1446. [PMID: 37222718 PMCID: PMC10389385 DOI: 10.1097/js9.0000000000000344] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Accepted: 03/09/2023] [Indexed: 05/25/2023]
Abstract
BACKGROUND Transarterial chemoembolisation (TACE) is the primary treatment for intermediate-stage hepatocellular carcinoma (HCC), according to the updated Barcelona Clinic Liver Cancer (BCLC) staging system. Although growing evidence favours liver resection (LR) over TACE for intermediate-stage HCC, the best treatment option remains controversial. This meta-analysis aimed to compare the overall survival (OS) after LR versus TACE for intermediate-stage HCC. METHODS A comprehensive literature review of PubMed, Embase, Cochrane Library, and Web of Science was performed. Studies that compared the efficacy of LR and TACE in patients with intermediate (BCLC stage B) HCC were selected. According to the recent updated BCLC classification, intermediate stage of HCC was defined as follows: (a) four or more HCC nodules of any size, or (b) two or three nodules, but if at least one tumour is larger than 3 cm. The main outcome was OS, expressed as the hazard ratio. RESULTS Nine eligible studies of 3355 patients were included in the review. The OS of patients who underwent LR was significantly longer than that of patients who underwent TACE (hazard ratio=0.52; 95% CI: 0.39-0.69; I2=79%). Prolonged survival following LR was confirmed after sensitivity analysis of five studies using propensity score matching (HR=0.45; 95% CI: 0.34-0.59; I2=55%). CONCLUSION Patients with intermediate-stage HCC who underwent LR had a longer OS that those who underwent TACE. The role of LR in patients with BCLC stage B should be clarified in future randomised controlled trials.
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Affiliation(s)
- Aleksandar Bogdanovic
- Clinic for Digestive Surgery
- School of Medicine, University of Belgrade, Belgrade, Serbia
| | - Jelena Djokic Kovac
- Center for Radiology and Magnetic Resonance Imaging, University Clinical Center of Serbia
- School of Medicine, University of Belgrade, Belgrade, Serbia
| | | | | | - Vladimir Dugalic
- Clinic for Digestive Surgery
- School of Medicine, University of Belgrade, Belgrade, Serbia
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Hsieh PM, Hsiao P, Chen YS, Yeh JH, Hung CM, Lin HY, Ma CH, Tang T, Huang YW, Cheng PN, Hsieh KC, Hu KC, Bair MJ, Lin CW. Clinical prognosis of surgical resection versus transarterial chemoembolization for single large hepatocellular carcinoma (≥5 cm): A propensity score matching analysis. Kaohsiung J Med Sci 2023; 39:302-310. [PMID: 36625289 DOI: 10.1002/kjm2.12640] [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: 10/11/2022] [Revised: 12/04/2022] [Accepted: 12/11/2022] [Indexed: 01/11/2023] Open
Abstract
Favorable prognostic factors and therapeutic strategies are important for patients with single large hepatocellular carcinoma (HCC). This retrospective study aimed to investigate the prognostic factors in patients with single large (≥5 cm) HCC with Child-Pugh (CP) class A patients and to recommend therapeutic strategies. Overall, 298 HCC patients with single and large (≥5 cm) tumors with CP class A, but without distant metastasis and macrovascular invasion were included, and their clinicopathological data, overall survival (OS), and progression-free survival (PFS) were recorded. OS and PFS was analyzed by the Kaplan-Meier method and Cox regression analysis. Propensity score matching (PSM) analysis was performed. The 298 HCC patients were 79.2% male and median age of 64 years. For the initial treatment, surgical resection (SR) and transarterial chemoembolization (TACE) was 50.8% and 49.2%, respectively. The OS and PFS were significantly higher in patients receiving SR than those receiving TACE before and after PSM. Furthermore, in multivariate analysis, cirrhosis (Hazard ratio [HR]: 2.04; 95% confidence interval [CI]: 1.35-3.03, p < 0.001, CP class A5/6 [HR: 4.01; 95% CI: 2.43-6.66, p < 0.001], and initial treatment [SR vs. TACE HR = 3.23; 95% CI: 2.13-5.01, p < 0.001]) remained significantly associated with mortality. Moreover, in multivariate analysis, CP class A5/6 (HR: 3.23; 95% CI: 1.89-5.88, p < 0.001), and initial treatment (Resection vs. TACE; HR = 4.17; 95% CI: 1.64-8.33, p = 0.039) remained significantly associated with recurrence. In conclusion, SR was associated with significantly higher OS and PFS rates than TACE before and after PSM for single large HCC patients.
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Affiliation(s)
- Pei-Min Hsieh
- Department of Surgery, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
| | - Pojen Hsiao
- Division of Gastroenterology and Hepatology, Department of Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.,Division of Gastroenterology and Hepatology, E-Da Dachang Hospital, I-Shou University, Kaohsiung, Taiwan.,School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Yaw-Sen Chen
- Department of Surgery, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.,School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Jen-Hao Yeh
- Division of Gastroenterology and Hepatology, Department of Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.,Division of Gastroenterology and Hepatology, E-Da Dachang Hospital, I-Shou University, Kaohsiung, Taiwan.,School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Chao-Ming Hung
- Department of Surgery, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.,School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Hung-Yu Lin
- Department of Surgery, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.,School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Ching-Hou Ma
- Department of Orthopedic Surgery, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
| | - TaoQian Tang
- Division of Gastroenterology and Hepatology, Department of Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.,Division of Gastroenterology and Hepatology, E-Da Dachang Hospital, I-Shou University, Kaohsiung, Taiwan
| | - Yu Wei Huang
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan.,Emergency and Critical Care Center, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.,School of Nursing, Fooyin University, Pingtung, Taiwan
| | - Pin-Nan Cheng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, National Cheng Kung University Hospital, Tainan, Taiwan
| | - Kun-Chou Hsieh
- Department of Surgery, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
| | - Kuang-Chun Hu
- Healthy Evaluation Center and Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan.,Mackay Junior College of Medicine, Nursing and Management, New Taipei, Taiwan
| | - Ming-Jong Bair
- Mackay Medical College, New Taipei, Taiwan.,Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, Taitung, Taiwan
| | - Chih-Wen Lin
- Division of Gastroenterology and Hepatology, Department of Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.,Division of Gastroenterology and Hepatology, E-Da Dachang Hospital, I-Shou University, Kaohsiung, Taiwan.,School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan.,Health Examination Center, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.,School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan.,Research Center for Traditional Chinese Medicine, China Medical University Hospital, Taichung, Taiwan
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8
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Zhang X, Jia N, Wang Y. Multi-input dense convolutional network for classification of hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Biomed Signal Process Control 2023. [DOI: 10.1016/j.bspc.2022.104226] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
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9
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Li YK, Zhao JF, Yang CL, Zhan GH, Zhang J, Qin SD, Zhou M, Li MJ, Huang JT, Kong FY, Huang H, Chen JH, Xiang BD. Effects of Clonorchis sinensis combined with Hepatitis B virus infection on the prognosis of patients with Hepatocellular Carcinoma following Hepatectomy. PLoS Negl Trop Dis 2023; 17:e0011012. [PMID: 36638133 PMCID: PMC9879467 DOI: 10.1371/journal.pntd.0011012] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2022] [Revised: 01/26/2023] [Accepted: 12/09/2022] [Indexed: 01/14/2023] Open
Abstract
BACKGROUND This study aimed to determine the impact of co-infection of Clonorchis sinensis (CS) and hepatitis B virus (HBV) on the prognosis of patients with hepatocellular carcinoma (HCC) following hepatectomy. METHODS The clinicopathological information of 946 patients with HCC following hepatectomy was retrospectively analyzed. The patients were divided into four groups depending on whether they had CS infection and/or HBV infection: double-negative group (infected with neither CS nor HBV), simple CS group (infected with only CS), simple HBV group (infected with only HBV), and double-positive group (co-infected with CS and HBV). Kaplan-Meier curves were used to evaluate the overall survival (OS) and recurrence-free survival (RFS), while log-rank tests were used to compare survival rates. Further, Cox regression was used to perform both univariate and multivariate survival analyses to identify variables linked to the prognosis of HCC. RESULTS The median overall survival (OS) and recurrence-free survival (RFS) in the double-positive, simple CS, simple HBV, and double-negative groups were 27 months and 9 months, 20 months and 7 months, 44 months and 12 months, and 42 months and 17 months, respectively. The double-positive group's 1-year, 3-year, and 5-year OS and RFS rates were 79.2% and 46.9%, 62.6% and 28.4%, 47.8%, and 12.2%, respectively. The simple CS group's 1-year, 3-year, and 5-year OS and RFS rates were 86.3% and 41.5%, 56.5% and 27.7%, 50.2%, and 18.5%, respectively. The simple HBV group's 1-year, 3-year, and 5-year OS and RFS rates were 89.8% and 56.0%, 72.5% and 30.5%, 63.8%, and 19.9%, respectively. The double-negative group's 1-year, 3-year, and 5-year OS and RFS rates were 91.5% and 62.3%, 76.1% and 32.9%, 64.0%, and 22.4%, respectively. Further, according to a Cox multivariate analysis, tumor size (> 5cm), Edmonson grade (III-IV), BCLC-C stage, and tumor satellite focus were independent risk factors for RFS and OS in patients with HCC. CONCLUSION Patients with HCC and Clonorchis sinensis infection experience a poor prognosis after hepatectomy, regardless of whether they are co-infected with HBV.
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Affiliation(s)
- Yuan-Kuan Li
- Department of Hepatobiliary Surgery, Guangxi Medical University Affiliated Tumor Hospital, Guangxi, China
| | - Jing-Fei Zhao
- Department of Hepatobiliary Surgery, Guangxi Medical University Affiliated Tumor Hospital, Guangxi, China
| | - Cheng-Lei Yang
- Department of Hepatobiliary Surgery, Guangxi Medical University Affiliated Tumor Hospital, Guangxi, China
| | - Guo-Hua Zhan
- Department of Hepatobiliary Surgery, Guangxi Medical University Affiliated Tumor Hospital, Guangxi, China
| | - Jie Zhang
- Department of Hepatobiliary Surgery, Guangxi Medical University Affiliated Tumor Hospital, Guangxi, China
| | - Shang-Dong Qin
- Department of Hepatobiliary Surgery, Guangxi Medical University Affiliated Tumor Hospital, Guangxi, China
| | - Min Zhou
- Department of Hepatobiliary Surgery, Guangxi Medical University Affiliated Tumor Hospital, Guangxi, China
| | - Min-Jun Li
- Department of Hepatobiliary Surgery, Guangxi Medical University Affiliated Tumor Hospital, Guangxi, China
| | - Jun-Tao Huang
- Department of Hepatobiliary Surgery, Guangxi Medical University Affiliated Tumor Hospital, Guangxi, China
| | - Feng-Yao Kong
- Department of Hepatobiliary Surgery, Guangxi Medical University Affiliated Tumor Hospital, Guangxi, China
| | - Hai Huang
- Department of Hepatobiliary Surgery, Guangxi Medical University Affiliated Wuming Hospital, Guangxi, China
| | - Jia-Hao Chen
- Department of Hepatobiliary Surgery, Guangxi Medical University Affiliated Wuming Hospital, Guangxi, China
| | - Bang-De Xiang
- Department of Hepatobiliary Surgery, Guangxi Medical University Affiliated Tumor Hospital, Guangxi, China
- * E-mail:
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10
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Su JY, Deng ZJ, Teng YX, Koh YX, Zhang WG, Zheng MH, Xie S, Huo RR, Chen CJ, Ma L, Zhong JH. Prognosis after hepatic resection of patients with hepatocellular carcinoma related to non-alcoholic fatty liver disease: meta-analysis. BJS Open 2023; 7:zrac167. [PMID: 36802244 PMCID: PMC9939291 DOI: 10.1093/bjsopen/zrac167] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Revised: 11/02/2022] [Accepted: 11/29/2022] [Indexed: 02/21/2023] Open
Abstract
BACKGROUND Whether the safety and efficacy of hepatic resection differ between patients whose hepatocellular carcinoma (HCC) is related to non-alcoholic fatty liver disease (NAFLD) or has other aetiologies is unknown. A systematic review was performed to explore potential differences between such conditions. METHODS PubMed, EMBASE, Web of Science, and Cochrane Library were systematically searched for relevant studies that reported hazard ratios (HRs) for overall and recurrence-free survival between patients with NAFLD-related HCC or HCC of other aetiologies. RESULTS The meta-analysis involved 17 retrospective studies involving 2470 patients (21.5 per cent) with NAFLD-related HCC and 9007 (78.5 per cent) with HCC of other aetiologies. Patients with NAFLD-related HCC were older and had higher body mass index (BMI), but were less likely to have cirrhosis (50.4 per cent versus 64.0 per cent, P < 0.001). The two groups suffered similar rates of perioperative complications and mortality. Patients with NAFLD-related HCC had slightly higher overall survival (HR 0.87, 95 per cent c.i. 0.75 to 1.02) and recurrence-free survival (HR 0.93, 95 per cent c.i. 0.84 to 1.02) than those with HCC of other aetiologies. In the various subgroup analyses, the only significant finding was that Asian patients with NAFLD-related HCC had significantly better overall survival (HR 0.82, 95 per cent c.i. 0.71 to 0.95) and recurrence-free survival (HR 0.88, 95 per cent c.i. 0.79 to 0.98) than Asian patients with HCC of other aetiologies. CONCLUSION The available evidence suggests that patients with NAFLD-related HCC have similar perioperative complications and mortality, but potentially longer overall and recurrence-free survival, compared with those with HCC of other aetiologies. Tailored surveillance strategies should be developed for patients with NAFLD without cirrhosis.
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Affiliation(s)
- Jia-Yong Su
- Hepatobiliary Surgery Department, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Zhu-Jian Deng
- Hepatobiliary Surgery Department, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Yu-Xian Teng
- Hepatobiliary Surgery Department, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Ye Xin Koh
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore
| | - Wan-Guang Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ming-Hua Zheng
- NAFLD Research Center, Department of Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Si Xie
- Hepatobiliary Surgery Department, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Rong-Rui Huo
- Hepatobiliary Surgery Department, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Chao-Jing Chen
- Hepatobiliary Surgery Department, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Liang Ma
- Hepatobiliary Surgery Department, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Jian-Hong Zhong
- Hepatobiliary Surgery Department, Guangxi Medical University Cancer Hospital, Nanning, China
- Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education; Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Nanning, China
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11
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Zhang J, Zhao J, Wei S, Huang P, Tu X, Su G, Gan Y, Gong W, Xiang B. Developing and Validating an Autophagy Gene-Set-Based Prognostic Signature in Hepatocellular Carcinoma Patients. Int J Gen Med 2022; 15:8399-8415. [DOI: 10.2147/ijgm.s388592] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Accepted: 11/17/2022] [Indexed: 11/29/2022] Open
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12
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Prognostic significance of combined α-fetoprotein and CA19-9 for hepatocellular carcinoma after hepatectomy. World J Surg Oncol 2022; 20:346. [PMID: 36258212 PMCID: PMC9580117 DOI: 10.1186/s12957-022-02806-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Accepted: 10/02/2022] [Indexed: 01/27/2023] Open
Abstract
Background The prognosis of hepatocellular carcinoma (HCC) varies considerably among patients with the same disease stage and characteristics, and only about two thirds show high levels of α-fetoprotein (AFP), a common prognostic indicator for HCC. Here, we assessed whether the combination of presurgical serum levels of AFP and carbohydrate antigen 19-9 (CA19-9) can predict the prognosis of HCC patients after hepatectomy. Methods The clinicopathological characteristics and post-hepatectomy outcomes of 711 HCC patients were retrospectively reviewed. The patients were classified into three groups based on whether their preoperative serum levels of both AFP and CA19-9 were higher than the respective cut-offs of 400 ng/ml and 37 U/ml [double positive (DP)], the level of only one marker was higher than the cut-off [single positive (SP)], or neither level was higher than the cut-off [negative (N)]. The overall survival (OS) and recurrence-free survival (RFS) rates were estimated using Kaplan–Meier curves. Univariate and multivariate survival analyses were performed to identify the clinicopathological factors significantly associated with HCC prognosis. Results The 1-year, 3-year, and 5-year RFS and OS rates in the N group were significantly higher than those in the SP group, while the DP group showed the lowest rates. Multivariate Cox regression analysis showed that large tumor size (> 5 cm), multiple tumors (≥ 2), incomplete tumor capsule, positive microvascular invasion, Barcelona Clinic Liver Cancer C stage, and CA19-9 level > 37 U/mL were independent risk factors for RFS and OS in HCC patients. Moreover, aspartate aminotransferase levels > 40 U/L proved to be an independent prognostic factor for OS. Conclusion The combination of serum AFP and CA19-9 levels may be a useful prognostic marker for HCC patients after hepatectomy.
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13
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Wu JY, Wu JY, Li YN, Qiu FN, Zhou SQ, Yin ZY, Chen YF, Li B, Zhou JY, Yan ML. Lenvatinib combined with anti-PD-1 antibodies plus transcatheter arterial chemoembolization for neoadjuvant treatment of resectable hepatocellular carcinoma with high risk of recurrence: A multicenter retrospective study. Front Oncol 2022; 12:985380. [PMID: 36212494 PMCID: PMC9534527 DOI: 10.3389/fonc.2022.985380] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2022] [Accepted: 09/06/2022] [Indexed: 01/27/2023] Open
Abstract
Background Early recurrence is common after surgical resection (SR) for hepatocellular carcinoma (HCC) with high risk of recurrence and is associated with poor prognosis. The combinations of lenvatinib (LEN), anti-PD-1 antibodies (PD-1) and transcatheter arterial chemoembolization (TACE) (triple therapy) has shown better trend in tumor response and survival outcomes on unresectable HCC. It is unknown whether triple therapy for neoadjuvant treatment of resectable HCC with high risk of recurrence is effective. This article aimed to compare the outcomes of surgery alone and neoadjuvant combination treatment with triple therapy before SR in patients with HCC with high risk of recurrence. Methods A retrospective study was conducted on patients diagnosed with HCC with high risk of recurrence who received treatment with or without triple therapy. The records of 24 patients in the triple therapy group and 76 patients in the surgery-alone group were analyzed. Propensity score matching (PSM) was performed to minimize the influence of potential confounders. Results One hundred patients were enrolled. In the triple therapy group, 8 (33.3%) and 12 (50.0%) patients had complete and partial responses, respectively, as assessed by an investigator. Before PSM, the overall survival (OS) rates for the triple therapy group at 6, 12, 18, and 24 months were 100.0%, 100.0%, 100.0%, and 85.7%, respectively, compared with corresponding 92.1%, 73.7%, 53.9%, and 48.7% for the surgery-alone group (P<0.001). The disease-free survival (DFS) rates were 82.2%, 66.95%, 48.8%, and 48.8% for the triple therapy and 41.92%, 28.34%, 27.05%, and 22.99% for the surgery-alone group (P=0.003). After PSM, DFS and OS were significantly longer in the triple therapy group than in the surgery-alone group (DFS, p=0.019; OS, p=0.003). Conclusions Neoadjuvant combination treatment before SR had a high rate of tumor response and provided significantly better postoperative survival outcomes than surgery alone in patients with HCC with high risk of recurrence.
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Affiliation(s)
- Jun-Yi Wu
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
- Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, China
| | - Jia-Yi Wu
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
- Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, China
| | - Yi-Nan Li
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
- Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, China
| | - Fu-Nan Qiu
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
- Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, China
| | - Song-Qiang Zhou
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
- Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, China
| | - Zhen-Yu Yin
- Department of Hepatobiliary Surgery, Xiamen Traditional Chinese Medical Hospital, Xiamen, China
| | - Yu-Feng Chen
- Department of Hepatobiliary Surgery, The Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, China
| | - Bin Li
- Department of Hepato-Biliary-Pancreatic and Vascular Surgery, The First Affiliated Hospital of Xiamen University, Xiamen, China
| | - Jian-Yin Zhou
- Department of Hepatobiliary Surgery, Zhongshan Hospital of Xiamen University, Xiamen, China
| | - Mao-Lin Yan
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
- Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, China
- *Correspondence: Mao-Lin Yan,
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Glantzounis GK, Korkolis D, Sotiropoulos GC, Tzimas G, Karampa A, Paliouras A, Asimakopoulos AG, Davakis S, Papalampros A, Moris D, Felekouras E. Individualized Approach in the Surgical Management of Hepatocellular Carcinoma: Results from a Greek Multicentre Study. Cancers (Basel) 2022; 14:cancers14184387. [PMID: 36139548 PMCID: PMC9496943 DOI: 10.3390/cancers14184387] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2022] [Revised: 09/04/2022] [Accepted: 09/05/2022] [Indexed: 01/27/2023] Open
Abstract
Simple Summary Hepatocellular carcinoma (HCC) is the most common primary liver cancer with expected increasing frequency in the next few decades. The Barcelona Clinic Liver Cancer (BCLC) Staging System is a widely adopted tool for guiding the therapeutic algorithms of patients with HCC. This classification has been guiding clinical practice for the last two decades. However, emerging data demonstrate that patients beyond the traditional criteria of operability or resectability can benefit from surgical treatment. We present the Greek multicentre experience of treating HCC within and beyond BCLC guidelines. Abstract Background: Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the third leading cause of death worldwide. The management of HCC is complex, with surgical treatment providing long-term survival in eligible patients. This study aims to present the experience of aggressive surgical management of HCC in Greece. Methods: This is a retrospective multicentre clinical study with 242 patients. Results: Most patients were male (79%) and had a median age of 71 yrs. According to the most recent BCLC criteria, 172 patients (71.1%) were classified as BCLC 0-A stage, 33 patients (13.6%) were classified as BCLC B, and 37 (15.3%) were classified as BCLC C. A total of 54% of the patients underwent major hepatectomy. Major postoperative morbidity was 15.6%, and the 90-day postoperative mortality rate was 4.5%. The median follow-up was 33.5 months. Three- and five-year overall survival was 65% and 48%, respectively. The median overall survival was 55 months. Significantly, five-year survival was 55% for BCLC A, and 34% and 21% for BCLC B and C, respectively. In univariate analysis, cirrhosis, type of resection (R status), and BCLC stage were associated with overall survival. Multivariate analysis indicated that R1 and R2 resections compared to R0, and BCLC C compared to BCLC 0-A, were independently associated with increased mortality. Conclusions: Aggressive surgical treatment of HCC offers satisfactory long-term survival prospects. A significant percentage (29%) of HCCs that underwent liver resection were of the intermediate and advanced BCLC stage. The management of patients with HCC should be discussed in multidisciplinary tumour board meetings on a case-by-case basis to be more effective.
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Affiliation(s)
- Georgios K. Glantzounis
- Hepatobiliary and Pancreatic Surgery (HPB) Unit, Department of Surgery, University Hospital of Ioannina, Faculty of Medicine, University of Ioannina, 45500 Ioannina, Greece
- Correspondence: ; Tel.: +302-651099695 or +306-984189292; Fax: +302-651099890
| | | | - Georgios C. Sotiropoulos
- Second Propedeutic Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, 11527 Athens, Greece
| | - Georgios Tzimas
- HPB Unit, Department of Surgery, Hygeia Hospital, 15123 Athens, Greece
| | - Anastasia Karampa
- Hepatobiliary and Pancreatic Surgery (HPB) Unit, Department of Surgery, University Hospital of Ioannina, Faculty of Medicine, University of Ioannina, 45500 Ioannina, Greece
| | - Athanasios Paliouras
- Hepatobiliary and Pancreatic Surgery (HPB) Unit, Department of Surgery, University Hospital of Ioannina, Faculty of Medicine, University of Ioannina, 45500 Ioannina, Greece
| | | | - Spyridon Davakis
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, 11527 Athens, Greece
| | - Alexandros Papalampros
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, 11527 Athens, Greece
| | - Dimitrios Moris
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, 11527 Athens, Greece
| | - Evangelos Felekouras
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, 11527 Athens, Greece
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15
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Benatatos N, Papadopoulou I, Assimakopoulos SF, Mulita F, Iliopoulos E, Germanos S, Vailas M, Kalogeropoulou C, Kitrou P, Maroulis I. Surgical management in hepatocellular carcinoma with portal vein tumour thrombosis: is this the end of the road or a chance to expand the criteria for resectability? PRZEGLAD GASTROENTEROLOGICZNY 2022; 17:257-265. [PMID: 36514454 PMCID: PMC9743323 DOI: 10.5114/pg.2022.118138] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Accepted: 05/19/2022] [Indexed: 12/16/2022]
Abstract
Portal vein thrombosis is a common complication associated with malignancies such as hepatocellular carcinoma, with a dismal and negative impact on prognosis. A thorough literature search in Pubmed and Google Scholar, under the terms 'hepatocellular carcinoma AND portal vein thrombosis', regarding the surgical management of portal vein thrombosis was conducted by the authors, and the associated results are presented in this narrative review. Precise classification of portal vein thrombosis and identification of subgroups of patients that will benefit from surgery is of paramount importance. Evolution of novel surgical techniques in liver resection and associated low morbidity and mortality rates in specialized hepatobiliary centres worldwide have been linked with promising results from the adoption of surgical management in these patients, when compared to systemic chemotherapy or arterial chemoembolization management that has traditionally been followed in such cases.
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Affiliation(s)
| | | | - Stelios F. Assimakopoulos
- Department of Internal Medicine and Infectious Diseases, University Hospital of Patras, Patras, Greece
| | - Francesk Mulita
- Department of Surgery, University Hospital of Patras, Patras, Greece
| | | | | | - Michail Vailas
- Department of Surgery, University Hospital of Patras, Patras, Greece
| | | | - Panagiotis Kitrou
- Department of Interventional Radiology, University Hospital of Patras, Patras, Greece
| | - Ioannis Maroulis
- Department of Surgery, University Hospital of Patras, Patras, Greece
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16
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Berardi G, Guglielmo N, Colasanti M, Meniconi RL, Ferretti S, Mariano G, Usai S, Angrisani M, Pecoraro A, Lucarini A, Gasparoli C, Ettorre GM. Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) for advanced hepatocellular carcinoma with macrovascular invasion. Updates Surg 2022; 74:927-936. [PMID: 35305261 DOI: 10.1007/s13304-022-01277-7] [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: 02/09/2022] [Accepted: 03/07/2022] [Indexed: 01/27/2023]
Abstract
Patients with advanced hepatocellular carcinoma (HCC) and macrovascular invasion (MVI) have dismal prognosis and are referred to systemic treatment or palliation. To investigate the outcomes of patients with HCC and MVI undergoing the associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) procedure. Demographics and operative data were retrospectively reviewed. All types of hepatectomies and all types of ALPPS modifications were included. MVI was categorized according to the Japanese Liver Cancer Study Group classification. 28 patients were included. Viral aetiology was the most common cause of chronic liver disease (89.3%). 85.7% of patients were cirrhotic, with a median MELD score of 9 (7-10). MVI of the hepatic veins or inferior vena cava was diagnosed in 46.4% of patients while portal vein involvement was present in 64.2% of cases. Four patients (14.2%) were diagnosed with bile duct involvement. No patients died after Step 1 while complications occurred in 21.4% of cases. Following step 2, 3 patients (11.5%) died and 20 (69.2%) developed complications. Grade B and C post-hepatectomy liver failure occurred in 57.6% and 11.5% of patients, respectively. After a median follow-up of 18 months (7-35), median survival was 22 months (3-40). Eleven patients (39.3%) recurred. Median disease-free survival was 15 months (5-26). The ALPPS procedure is an extreme rescue approach in otherwise inoperable advanced HCC with MVI. The procedure is associated with high morbidity and mortality and patients' selection is pivotal. Oncological outcomes are safe and should be further investigated.
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Affiliation(s)
- Giammauro Berardi
- Department of General Surgery and Liver Transplantation, San Camillo Forlanini Hospital of Rome, Circonvallazione Gianicolense 87, 00152, Rome, Italy.
| | - Nicola Guglielmo
- Department of General Surgery and Liver Transplantation, San Camillo Forlanini Hospital of Rome, Circonvallazione Gianicolense 87, 00152, Rome, Italy
| | - Marco Colasanti
- Department of General Surgery and Liver Transplantation, San Camillo Forlanini Hospital of Rome, Circonvallazione Gianicolense 87, 00152, Rome, Italy
| | - Roberto Luca Meniconi
- Department of General Surgery and Liver Transplantation, San Camillo Forlanini Hospital of Rome, Circonvallazione Gianicolense 87, 00152, Rome, Italy
| | - Stefano Ferretti
- Department of General Surgery and Liver Transplantation, San Camillo Forlanini Hospital of Rome, Circonvallazione Gianicolense 87, 00152, Rome, Italy
| | - Germano Mariano
- Department of General Surgery and Liver Transplantation, San Camillo Forlanini Hospital of Rome, Circonvallazione Gianicolense 87, 00152, Rome, Italy
| | - Sofia Usai
- Department of General Surgery and Liver Transplantation, San Camillo Forlanini Hospital of Rome, Circonvallazione Gianicolense 87, 00152, Rome, Italy
| | - Marco Angrisani
- Department of General Surgery and Liver Transplantation, San Camillo Forlanini Hospital of Rome, Circonvallazione Gianicolense 87, 00152, Rome, Italy
| | - Alessandra Pecoraro
- Department of General Surgery and Liver Transplantation, San Camillo Forlanini Hospital of Rome, Circonvallazione Gianicolense 87, 00152, Rome, Italy
| | - Alessio Lucarini
- Department of General Surgery and Liver Transplantation, San Camillo Forlanini Hospital of Rome, Circonvallazione Gianicolense 87, 00152, Rome, Italy
| | - Camilla Gasparoli
- Department of General Surgery and Liver Transplantation, San Camillo Forlanini Hospital of Rome, Circonvallazione Gianicolense 87, 00152, Rome, Italy
| | - Giuseppe Maria Ettorre
- Department of General Surgery and Liver Transplantation, San Camillo Forlanini Hospital of Rome, Circonvallazione Gianicolense 87, 00152, Rome, Italy
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17
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Xu JX, Xing WT, Peng YC, Chen YY, Qi LN. Outcomes of postoperative adjuvant transarterial chemoembolization for hepatocellular carcinoma according to the Ki67 index. Future Oncol 2022; 18:2113-2125. [PMID: 35266821 DOI: 10.2217/fon-2021-1443] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023] Open
Abstract
Aim: To assess whether Ki67 is related to the efficacy of postoperative adjuvant transarterial chemoembolization (PA-TACE) in hepatocellular carcinoma patients at high risk of postsurgical recurrence. Methods: A total of 716 patients undergoing surgical resection with or without PA-TACE were retrospectively enrolled. Immunohistochemistry was used to analyze Ki67 expression. Results: There was no significant difference in tumor-free survival between patients who underwent resection with or without chemoembolization. However, chemoembolization was associated with significantly higher tumor-free survival rates among patients with 'low' (<30%) or 'moderate' (30-59%) levels of Ki67. Patients highly expressing Ki67 displayed higher rates of overall recurrence, earlier recurrence, multiple intrahepatic recurrence and extrahepatic metastasis. Conclusion: In patients with relatively high Ki67 levels, PA-TACE does not appear to improve outcomes.
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Affiliation(s)
- Jing-Xuan Xu
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, 530021, Guangxi Province, China.,Key Laboratory of Early Prevention & Treatment for Regional High Frequency Tumor, Ministry of Education, Nanning, 530021, Guangxi Province, China
| | - Wan-Ting Xing
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, 530021, Guangxi Province, China.,Key Laboratory of Early Prevention & Treatment for Regional High Frequency Tumor, Ministry of Education, Nanning, 530021, Guangxi Province, China
| | - Yu-Chong Peng
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, 530021, Guangxi Province, China.,Key Laboratory of Early Prevention & Treatment for Regional High Frequency Tumor, Ministry of Education, Nanning, 530021, Guangxi Province, China
| | - Yuan-Yuan Chen
- Department of Ultrasound, First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China
| | - Lu-Nan Qi
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, 530021, Guangxi Province, China.,Guangxi Liver Cancer Diagnosis & Treatment Engineering & Technology Research Center, Nanning, 530021, Guangxi Province, China.,Key Laboratory of Early Prevention & Treatment for Regional High Frequency Tumor, Ministry of Education, Nanning, 530021, Guangxi Province, China
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18
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Deng ZJ, Li L, Teng YX, Zhang YQ, Zhang YX, Liu HT, Huang JL, Liu ZX, Ma L, Zhong JH. Treatments of Hepatocellular Carcinoma with Portal Vein Tumor Thrombus: Current Status and Controversy. J Clin Transl Hepatol 2022; 10:147-158. [PMID: 35233384 PMCID: PMC8845160 DOI: 10.14218/jcth.2021.00179] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2021] [Revised: 06/30/2021] [Accepted: 07/12/2021] [Indexed: 01/27/2023] Open
Abstract
The proportions of patients with hepatocellular carcinoma (HCC) involving portal vein tumor thrombus (PVTT) varies greatly in different countries or regions, ranging from 13% to 45%. The treatment regimens for PVTT recommended by HCC guidelines in different countries or regions also vary greatly. In recent years, with the progress and development of surgical concepts, radiotherapy techniques, systematic therapies (for example, VEGF inhibitors, tyrosine kinase inhibitors and immune checkpoint inhibitors), patients with HCC involving PVTT have more treatment options and their prognoses have been significantly improved. To achieve the maximum benefit, both clinicians and patients need to think rationally about the indications of treatment modalities, the occurrence of severe adverse events, and the optimal fit for the population. In this review, we provide an update on the treatment modalities available for patients with HCC involving PVTT. Trials with large sample size for patients with advanced or unresectable HCC are also reviewed.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Liang Ma
- Correspondence to: Jian-Hong Zhong and Liang Ma, Hepatobiliary Surgery Department, Guangxi Medical University Cancer Hospital, Nanning, Guangxi 530021, China. ORCID: https://orcid.org/0000-0002-1494-6396 (JHZ), https://orcid.org/0000-0001-8106-373X (LM). Tel/Fax: +86-771-5301253, E-mail: (JHZ), (LM)
| | - Jian-Hong Zhong
- Correspondence to: Jian-Hong Zhong and Liang Ma, Hepatobiliary Surgery Department, Guangxi Medical University Cancer Hospital, Nanning, Guangxi 530021, China. ORCID: https://orcid.org/0000-0002-1494-6396 (JHZ), https://orcid.org/0000-0001-8106-373X (LM). Tel/Fax: +86-771-5301253, E-mail: (JHZ), (LM)
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19
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Duan X, Liu J, Han X, Ren J, Li H, Li F, Ju S. Comparison of Treatment Response, Survival Profiles, as Well as Safety Profiles Between CalliSpheres ® Microsphere Transarterial Chemoembolization and Conventional Transarterial Chemoembolization in Huge Hepatocellular Carcinoma. Front Oncol 2022; 11:793581. [PMID: 35127501 PMCID: PMC8814413 DOI: 10.3389/fonc.2021.793581] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Accepted: 12/15/2021] [Indexed: 12/11/2022] Open
Abstract
Purpose CalliSpheres® microspheres (CSM) are the first drug-eluting beads (DEB) developed in China. This study aimed to compare treatment response, survival, and safety profiles between DEB transarterial chemoembolization (DEB-TACE) with CSM and conventional TACE (cTACE) in huge hepatocellular carcinoma (HCC) patients. Methods A total of 71 patients with huge HCC who underwent DEB-TACE or cTACE were consecutively enrolled in this retrospective cohort study. Treatment response was assessed at first month (M1), third month (M3), and sixth month (M6) after TACE therapy; progression-free survival (PFS) and overall survival (OS) were evaluated; liver function indexes were recorded before TACE operation (M0), at first week (W1), M1 and M6 after TACE therapy; adverse events which occurred after TACE operation were recorded. Results DEB-TACE presented with higher objective response rate (60.0% vs. 29.7%, p < 0.05) and disease control rate (86.7% vs. 59.4%, p < 0.05) compared with cTACE at M3. Regarding survival profiles, PFS [median: 3.3 months (95% CI: 2.8–3.7) vs. 2.1 months (95% CI: 1.7–2.5)] as well as OS [median: 7.8 months (95% CI: 4.6–11.0) vs. 5.7 months (95% CI: 5.0–6.3)] were longer in DEB-TACE group compared with cTACE group (both p < 0.01). Multivariate Cox’s regression further illustrated that DEB-TACE vs. cTACE was an independent protective factor for PFS and OS (both p < 0.01). As for safety profiles, patients’ liver function injury was reduced in the DEB-TACE group compared with the cTACE group. The incidence of fever was lower, and CINV was less severe in the DEB-TACE group compared with the cTACE group (both p < 0.05), while no difference in occurrence of liver abscess, increase of ascites, or moderate pain between two groups was observed. Conclusion DEB-TACE with CSM presents with better treatment response, survival profiles, as well as safety profiles compared with cTACE in treatment for huge HCC patients.
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Affiliation(s)
- Xuhua Duan
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Juanfang Liu
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Xinwei Han
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Jianzhuang Ren
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Hao Li
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Fengyao Li
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Shuguang Ju
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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Elsanousi OM, Mohamed MA, Salim FH, Adam EA, Bedri S. Long-term outcome of novel combined surgical-injection treatment (COSIT) for large hepatocellular carcinoma: Stage 2A IDEAL prospective case series. Ann Med Surg (Lond) 2021; 72:103098. [PMID: 34888043 PMCID: PMC8636767 DOI: 10.1016/j.amsu.2021.103098] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Accepted: 11/20/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Large hepatocellular carcinoma (HCC) treatment options have obvious limitations. Our trial comprises ipsilateral hepatic artery ligation and extrahepatic collaterals division (HALED, reinforced by percutaneous tumor injection controlling residual HCC arterial supply. We aimed to evaluate the long term safety and feasibility of the Combined Surgical and Injection of alcohol Treatment (COSIT) as a novel therapy for the large HCC. MATERIAL AND METHODS Candidates' clinical data of the of this case series were prospectively and sequentially reported in accordance with stage 2a development IDEAL (Idea, Development, Exploration, Assessment and Long-term monitoring) recommendations. It included adult patients with HCC (diameter >5 cm) subjected to COSIT coming to our center during a five years' trial evaluating the long term outcome measures. Study ID (NCT03138044 ClinicalTrials.gov). RESULTS Patients were 21, their mean age (±standard deviation) was 61·9 (±9·3) years. Eleven (52.4%) patients had tumors diameter >10 cm. 17 (80.9%) patients were advanced BCLC stage. Six modifications were made in this injection phase till it came to a stability. The mean alcohol volume was 72.0 mls. The mean follow-up duration was 16 months. The median overall survival duration was 14 months. The one, three and five years' survival was 71.4%, 23.8% and 4.8%, respectively. Grade 3/4 and 4 Common Toxicity Criteria for Adverse Effects (v4.03) were encountered in 10 (47.6%) and one (4.8%) patients, respectively. CONCLUSION This preliminary findings of COSIT can be a promising alternative treatment for patients having large HCC. Consequently, a multicenter stage 2b Exploration IDEAL trial is suggested.
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Affiliation(s)
- Osama M. Elsanousi
- Department of Surgery, Ribat University Hospital, Faculty of Medicine, The National Ribat University, Sudan
| | | | - Fatima H. Salim
- Department of Medicine, Ribat University Hospital, Faculty of Medicine, The National Ribat University, Sudan
| | - Elsadig A. Adam
- Department of Pathology, Ribat University Hospital, Faculty of Medicine, The National Ribat University, Sudan
| | - Shahinaz Bedri
- Pathology Unit School of Medicine, Ahfad University for Women, P. O. Box: 167, Omdurman, Sudan
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Yamamoto M, Kobayashi T, Honmyo N, Oshita A, Abe T, Kohashi T, Onoe T, Fukuda S, Omori I, Imaoka Y, Ohdan H. Liver resection is associated with good outcomes for hepatocellular carcinoma patients beyond the Barcelona Clinic Liver Cancer criteria: A multicenter study with the Hiroshima Surgical study group of Clinical Oncology. Surgery 2021; 171:1303-1310. [PMID: 34756748 DOI: 10.1016/j.surg.2021.09.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Revised: 09/09/2021] [Accepted: 09/11/2021] [Indexed: 01/27/2023]
Abstract
BACKGROUND Liver resection for hepatocellular carcinoma beyond the Barcelona Clinic Liver Cancer criteria remains controversial. Strict candidate selection is crucial to achieve optimal results in this population. This study explored postoperative outcomes and developed a preoperative predictive formula to identify patients most likely to benefit from liver resection. METHODS In total, 382 patients who underwent liver resection for hepatocellular carcinoma beyond the Barcelona Clinic Liver Cancer resection criteria between 2000 and 2017 were identified from a multicenter database with the Hiroshima Surgical study group of Clinical Oncology. An overall survival prediction model was developed, and patients were classified by risk status. RESULTS The 5-year overall survival after curative resection was 50.0%. Overall survival multivariate analysis identified that a high a-fetoprotein level, macrovascular invasion, and high total tumor burden were independent prognostic risk factors; these factors were used to formulate risk scores. Patients were divided into low-, moderate-, and high-risk groups; the 5-year overall survival was 65.7%, 49.5%, and 17.0% (P < .001), and the 5-year recurrence-free survival was 31.3%, 26.2%, and 0%, respectively (P < .001). The model performance was good (C-index, 0.76). Both the early and extrahepatic recurrence increased with higher risk score. CONCLUSION The prognosis of patients with hepatocellular carcinoma beyond the Barcelona Clinic Liver Cancer resection criteria depended on a high a-fetoprotein level, macrovascular invasion, and high total tumor burden, and risk scores based on these factors stratified the prognoses. Liver resection should be considered in patients with hepatocellular carcinoma beyond the Barcelona Clinic Liver Cancer criteria with a low or moderate-risk score.
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Affiliation(s)
- Masateru Yamamoto
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Tsuyoshi Kobayashi
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan.
| | - Naruhiko Honmyo
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Akihiko Oshita
- Department of Gastroenterological Surgery, Hiroshima Prefectural Hospital, Hiroshima, Japan
| | - Tomoyuki Abe
- Department of Surgery, Onomichi General Hospital, Onomichi, Japan
| | - Toshihiko Kohashi
- Department of Surgery, Hiroshima City Asa Citizens Hospital, Hiroshima, Japan
| | - Takashi Onoe
- National Hospital Organization, Kure Medical Center/Chugoku Cancer Center, Institute for Clinical Research, Hiroshima, Japan
| | - Saburo Fukuda
- Department of Surgery, Chugoku Rosai Hospital, Kure, Japan
| | - Ichiro Omori
- Department of Surgery, National Hospital Organization Higashihiroshima Medical Center, Hiroshima, Japan
| | - Yasuhiro Imaoka
- Department of Surgery, National Hospital Organization Hiroshima-Nishi Medical Center, Hiroshima, Japan
| | - Hideki Ohdan
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
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Romano F, Chiarelli M, Garancini M, Scotti M, Zago M, Cioffi G, De Simone M, Cioffi U. Rethinking the Barcelona clinic liver cancer guidelines: Intermediate stage and Child-Pugh B patients are suitable for surgery? World J Gastroenterol 2021; 27:2784-2794. [PMID: 34135554 PMCID: PMC8173387 DOI: 10.3748/wjg.v27.i21.2784] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2021] [Revised: 02/24/2021] [Accepted: 04/29/2021] [Indexed: 02/06/2023] Open
Abstract
According to Barcelona Clinic Liver Cancer recommendations, intermediate stage hepatocellular carcinomas (stage B) are excluded from liver resection and are referred to palliative treatment. Moreover, Child-Pugh B patients are not usually candidates for liver resection. However, many hepatobiliary centers in the world manage patients with intermediate stage hepatocellular carcinoma or Child-Pugh B cirrhosis with liver resection, maintaining that hepatic resection is not contraindicated in selected patients with non–early-stage hepatocellular carcinoma and without normal liver function. Several studies demonstrate that resection provides the best survival benefit for selected patients in very early/early and even in intermediate stages of Barcelona Clinic Liver Cancer classification, and this treatment gives good results in the setting of multinodular, large tumors in patients with portal hypertension and/or Child-Pugh B cirrhosis. In this review we explore this controversial topic, and we show through the literature analysis how liver resection may improve the short- and long-term survival rate of carefully selected Barcelona Clinic Liver Cancer B and Child-Pugh B hepatocellular carcinoma patients. However, other large clinical studies are needed to clarify which patients with intermediate stage hepatocellular carcinoma are most likely to benefit from liver resection.
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Affiliation(s)
- Fabrizio Romano
- Department of Surgery, School of Medicine and Surgery, University of Milano-Bicocca, Monza 20900, Italy
| | - Marco Chiarelli
- Emergency and Robotic Surgery, A. Manzoni Hospital, ASST Lecco, Lecco 23900, Italy
| | - Mattia Garancini
- Department of General Surgery, San Gerardo Hospital, Monza 20900, Italy
| | - Mauro Scotti
- Department of General Surgery, San Gerardo Hospital, Monza 20900, Italy
| | - Mauro Zago
- Emergency and Robotic Surgery, A. Manzoni Hospital, ASST Lecco, Lecco 23900, Italy
| | - Gerardo Cioffi
- Department of Sciences and Technologies, Università degli Studi del Sannio di Benevento, Benevento 82100, Italy
| | | | - Ugo Cioffi
- Department of Surgery, University of Milan, Milano 20122, Italy
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23
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Zhou TY, Chen SQ, Wang HL, Weng SM, Zhou GH, Zhang YL, Nie CH, Zhu TY, Wang BQ, Yu ZN, Jing L, Chen F, Sun JH. Safety and efficacy of drug-eluting bead transarterial chemoembolization with CalliSpheres® microsphere for hepatocellular carcinoma with portal vein tumor thrombus: a preliminary study. J Cancer 2021; 12:4522-4529. [PMID: 34149916 PMCID: PMC8210571 DOI: 10.7150/jca.54650] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2020] [Accepted: 05/18/2021] [Indexed: 12/11/2022] Open
Abstract
Objective: To prospectively evaluate the safety and therapeutic effectiveness of drug-eluting beads transcatheter arterial chemoembolization (DEB-TACE) with CalliSpheres® microsphere (CSM) for the treatment of hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT), and to analyze the prognostic factors. Method: Between November 2015 and November 2017, consecutive 58 HCC patients with PVTT who received DEB-TACE with CSM treatment were prospectively enrolled in this study. The demographic characteristics, adverse events (AEs) and treatment response were collected. Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were performed to determine the independent factors correlated with OS. Results: The objective response rate (ORR) was 79.3% in terms of tumors and 44.8% in thrombi. The median PFS and OS of patients were 5.0 months and 9.0 months respectively. The cumulative survival rate at 3-, 6-, 9-, 12-, 18- and 24-month were 94.8%, 72.4%, 53.4%, 41.4%, 22.4% and 19.0%, respectively. In a stepwise multivariate Cox proportional hazards model, the higher Child-Pugh classification (HR=2.279; 95%CI, 1.042-4.985, p = 0.039) and tumor burden (p = 0.008) were the significant predictors of poorer OS after adjustment for known risk factors. The most common clinical AEs were postembolization syndrome (PES) and the most prevalent laboratory toxicity was transient liver function damage. Conclusion: DEB-TACE with CSM is safe and well-tolerated in HCC patients with PVTT, and reveals a favorable preliminary clinical outcome. The higher Child-Pugh classification and liver tumor burden are independent prognostic factors associated with poor survival for HCC patients with PVTT treated by DEB-TACE with CSM.
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Affiliation(s)
- Tan-Yang Zhou
- Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.,Zhejiang Provincial Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou, Zhejiang Province, China
| | - Sheng-Qun Chen
- Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.,Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou 310003, Zhejiang Province, China
| | - Hong-Liang Wang
- Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.,Zhejiang Provincial Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou, Zhejiang Province, China
| | - Sheng-Ming Weng
- Department of Radiology, Jingning County People's Hospital, Lishui, Zhejiang Province, China
| | - Guan-Hui Zhou
- Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.,Zhejiang Provincial Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou, Zhejiang Province, China
| | - Yue-Lin Zhang
- Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.,Zhejiang Provincial Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou, Zhejiang Province, China
| | - Chun-Hui Nie
- Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.,Zhejiang Provincial Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou, Zhejiang Province, China
| | - Tong-Yin Zhu
- Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.,Zhejiang Provincial Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou, Zhejiang Province, China
| | - Bao-Quan Wang
- Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.,Zhejiang Provincial Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou, Zhejiang Province, China
| | - Zi-Niu Yu
- Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.,Zhejiang Provincial Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou, Zhejiang Province, China
| | - Li Jing
- Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.,Zhejiang Provincial Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou, Zhejiang Province, China
| | - Feng Chen
- Department of Radiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jun-Hui Sun
- Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.,Zhejiang Provincial Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou, Zhejiang Province, China.,Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou 310003, Zhejiang Province, China
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24
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Shehta A, Farouk A, Elghawalby AN, Elshobary M, Aboelenin A, Fouad A, Ali MA. Outcomes of Hepatic Resection for Hepatocellular Carcinoma Associated with Portal Vein Invasion. J Surg Res 2021; 266:269-283. [PMID: 34038849 DOI: 10.1016/j.jss.2021.04.011] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Revised: 04/02/2021] [Accepted: 04/10/2021] [Indexed: 01/27/2023]
Abstract
BACKGROUND To evaluate our experience of liver resection for hepatocellular carcinoma (HCC) patients associated with macroscopic portal vein invasion (PVI). METHODS Consecutive HCC patients who underwent liver resection for HCC between November 2009 & June 2019 were included. To overcome selection bias between patients with and without macroscopic PVI, we performed 1:1 match using propensity score matching (PSM). RESULTS Macroscopic PVI was detected in 37 patients (12.8%). We divided our patients into two groups according to the presence of macroscopic PVI. After PSM, 36 patients of PVI group were matched with 36 patients from Non-PVI group. After PSM, both groups were well balanced regarding tumor site, number, liver resection extent and type. Longer operation time and more blood loss were noted in PVI group. Higher incidence of post-operative morbidities occurred in PVI group especially, post-hepatectomy liver dysfunction. The 1-, 2-, and 3-y overall survival rates for Non-PVI group were 85.3%, 64.6%, and 64.6% & 69.8%, 42%, and 0% for PVI group, respectively (P = 0.009). There were no significant differences regarding the recurrence rate, site, and its management. The 1-, 2-, and 3-y disease-free survival (DFS) rates for Non-PVI group were 81.7%, 72.3%, and 21.7% & 67.7%, 42.3%, and 0% for PVI group, respectively (P = 0.172). CONCLUSION Surgical management of advanced HCCs with macroscopic PVI is feasible, and associated with comparable DFS but poorer overall survival, compared to patients without PVI.
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Affiliation(s)
- Ahmed Shehta
- Gastrointestinal Surgery Center, Department of Surgery, College of Medicine, Mansoura University, Mansoura, Egypt.
| | - Ahmed Farouk
- Gastrointestinal Surgery Center, Department of Surgery, College of Medicine, Mansoura University, Mansoura, Egypt
| | - Ahmed Nabieh Elghawalby
- Gastrointestinal Surgery Center, Department of Surgery, College of Medicine, Mansoura University, Mansoura, Egypt
| | - Mohamed Elshobary
- Gastrointestinal Surgery Center, Department of Surgery, College of Medicine, Mansoura University, Mansoura, Egypt
| | - Ahmed Aboelenin
- Gastrointestinal Surgery Center, Department of Surgery, College of Medicine, Mansoura University, Mansoura, Egypt
| | - Amgad Fouad
- Gastrointestinal Surgery Center, Department of Surgery, College of Medicine, Mansoura University, Mansoura, Egypt
| | - Mahmoud Abdelwahab Ali
- Gastrointestinal Surgery Center, Department of Surgery, College of Medicine, Mansoura University, Mansoura, Egypt
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25
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Development of a preoperative prognostic scoring system to predict benefits of hepatic resection in advanced hepatocellular carcinoma patients. Biosci Rep 2021; 41:228134. [PMID: 33835138 PMCID: PMC8035620 DOI: 10.1042/bsr20201928] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Revised: 02/26/2021] [Accepted: 03/09/2021] [Indexed: 02/08/2023] Open
Abstract
Objective: The present study aimed to identify risk factors for overall survival in advanced hepatocellular carcinoma (HCC) patients and establish a scoring system to select patients who would benefit from hepatic resection. Methods: Survival curves were analyzed using the Kaplan–Meier method and log-rank test. The prognostic scoring system was developed from training cohort using a Cox-regression model and validated in a external validation cohort Results: There were 401 patients in the training cohort, 163 patients in the external validation cohorts. The training cohort median survival in all patients was 12 ± 1.07 months, rate of overall survival was 49.6% at 1 year, 25.0% at 3 years, and 18.0% at 5 years. A prognostic scoring system was established based on age, body mass index, alkaline phosphatase, tumor number and tumor capsule. Patients were classified as low- risk group(≤3.5) or high-risk group(>3.5). High-risk patients had a median survival of 9 months, compared with 23 months in low-risk patients. The area under the receiver operating characteristic curve (AUC) of the prognostic scoring system was 0.747 (0.694–0.801), which is significantly better than AFP, Child-Pugh and ALBI. The AUC of validation cohorts was 0.716 (0.63–0.803). Conclusion: A prognostic scoring system for hepatic resection in advanced HCC patients has been developed based entirely on preoperative variables. Patients classified as low risk using this system may experience better prognosis after hepatic resection.
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Abstract
Hepatocellular carcinoma (HCC) is a lethal malignancy with poor prognosis. More than 80% of patients are diagnosed at an advanced stage, and most patients with HCC also have liver cirrhosis that complicates cancer management. No targeted treatment options currently exist outside genomics-based clinical trials. Multiple tyrosine kinase inhibitors (mTKIs) such as sorafenib, lenvatinib, cabozantinib, and regorafenib have been used to treat advanced hepatocellular carcinoma (aHCC). Immune checkpoint inhibitors including nivolumab and pembrolizumab have shown survival benefit. More recently, atezolizumab in combination with bevacizumab resulted in improved overall survival and progression-free survival, compared with sorafenib in patients with aHCC in the first-line setting. The combination of nivolumab with ipilimumab as an alternative in the treatment of patients treated with sorafenib has inspired various combination studies of immune checkpoint inhibitors. Currently, ongoing studies of systemic therapy consist of various immune-based combination therapies. Finally, there is no established adjuvant and neoadjuvant therapy although a few early phase studies show promising results. In this chapter, we summarize current approaches of systemic treatment in patients with liver cancer.
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Affiliation(s)
- Tarik Demir
- Department of Gastrointestinal Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, United States
| | - Sunyoung S Lee
- Department of Gastrointestinal Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, United States
| | - Ahmed O Kaseb
- Department of Gastrointestinal Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, United States.
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Kang KJ, Ahn KS. Is the Barcelona Clinic Liver Cancer guideline for treating intermediate to advanced staged hepatocellular carcinoma still appropriate? ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:1. [PMID: 33553294 PMCID: PMC7859792 DOI: 10.21037/atm-2020-132] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Affiliation(s)
- Koo Jeong Kang
- Division of Hepatobiliary-Pancreatic Surgery, Department of Surgery, School of Medicine, Keimyung University, Dongsan Hospital, Daegu, Republic of Korea
| | - Keun Soo Ahn
- Division of Hepatobiliary-Pancreatic Surgery, Department of Surgery, School of Medicine, Keimyung University, Dongsan Hospital, Daegu, Republic of Korea
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Mohammadifard M, Ghanaati H, Mohammadifard M. A review of applying transarterial chemoembolization (TACE) method for management of hepatocellular carcinoma. J Family Med Prim Care 2021; 10:3553-3560. [PMID: 34934646 PMCID: PMC8653440 DOI: 10.4103/jfmpc.jfmpc_2347_20] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2020] [Revised: 06/16/2021] [Accepted: 06/28/2021] [Indexed: 12/09/2022] Open
Abstract
Liver cancer is one of the most ordinary reasons for death among cancers. Hepatocellular carcinoma (HCC) is the most common type of liver cancer. In spite of the fact that various remedial methods have been approved particularly the survival effects of the transcatheter arterial chemoembolization (TACE) method have been accomplished widely in the HCC treatment. By applying the TACE method correctly, good survival outcomes can be achieved without harmfully affecting the hepatic functions. Transarterial chemoembolization mixes the effect of avascular necrosis (AVN) with the effect of regional chemotherapy those are under the influence of arterial embolization. By knowing the fact that the metastases of liver cancer and also perfusion indices in hepatocellular carcinoma (HCC) are via hepatic arteries, doctors chose the TACE method for the treatment of liver cancer. On the other hand, in this method, the radiologists can easily convey antitumor remedies via the arteries. Anyway, medium-level HCC is a sensitive stage of the heterogeneous disease that many patients suffer from, so specialists must consider it as a hazardous syndrome. The TACE procedure could be applied just in cases that the liver function of patients is appropriate yet, the patient liver portal vein do not have any problems and the patients do not have ascites disorder. This review is aimed to figure out the evident advantages of TACE especially by a comprehensive view on the medium level HCC. Because of that this treatment method is suggested as a first-line remedy. At last, the future landscape of the initial factors of research in managing HCC disorders have been summarized.
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Guan R, Hong W, Huang J, Peng T, Zhao Z, Lin Y, Yu M, Jian Z. The expression and prognostic value of GLYATL1 and its potential role in hepatocellular carcinoma. J Gastrointest Oncol 2020; 11:1305-1321. [PMID: 33457003 PMCID: PMC7807277 DOI: 10.21037/jgo-20-186] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2020] [Accepted: 09/20/2020] [Indexed: 01/17/2023] Open
Abstract
BACKGROUND Glycine-N-acyltransferase-like 1 (GLYATL1), which is involved in the detoxification of endogenous and exogenous acyl-CoA, promotes glutamine metabolism in xenobiotic metabolism. Recent evidence suggests an association between GLYATL1 and tumors. However, there are few comprehensive analyses of GLYATL1 in cancers. We evaluated the expression and prognostic value of GLYATL1 and explored the mechanism underlying the association between GLYATL1 and cancers. METHODS GLYATL1 mRNA expression across cancers was investigated in the Oncomine database and confirmed in the UALCAN and Gene Expression Profiling Interactive Analysis (GEPIA) databases. Next, its prognostic value in different cancers was revealed by PrognoScan and Kaplan-Meier plotter. According to clinicopathologic features, we conducted a subgroup analysis of the prognosis of GLYATL1 in a cohort of hepatocellular carcinoma (HCC) patients from The Cancer Genome Atlas (TCGA) and the GSE116174 dataset. We further investigated the GLYATL1 promoter methylation profile in HCC. Next, a protein-protein interaction (PPI) network was constructed via the Search Tool for the Retrieval of Interacting Genes (STRING) database. Finally, we utilized gene set enrichment analysis (GSEA) to identify significantly enriched pathways and confirmed their associations using the Tumor Immune Estimation Resource (TIMER) and GEPIA databases. RESULTS GLYATL1 is downregulated in many cancers and indicates a poor prognosis. Specifically, low GLYATL1 expression was associated with short overall survival (OS) in HCC patients. Interestingly, GLYATL1 expression was associated with poor OS in stage I-II HCC patients and was revealed as an independent prognostic factor. The promoter methylation level of GLYATL1 in HCC tissue was significantly higher than that in normal liver tissue. The PPI network suggested that GLYATL1 is co-expressed with ten genes, including CNGA3 and GNB5. GSEA revealed that GLYATL1 is predominantly negatively enriched in xenobiotic metabolism, and the gene association analysis in TIMER and GEPIA showed a significantly negative association between the expression of GLYATL1 and the expression of most genes involved in mitochondrial glutamine metabolism, including SLC1A5 and SLC1A11. CONCLUSIONS Our study is the first to shed light on the expression and prognostic value of GLYATL1 in cancers and provide a potential regulatory mechanism underlying HCC development.
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Affiliation(s)
- Renguo Guan
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Weifeng Hong
- Department of Medical Imaging, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
| | - Jianfeng Huang
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Tianyi Peng
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Zhen Zhao
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Ye Lin
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Min Yu
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Zhixiang Jian
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
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Wang L, Wang W, Rong W, Li Z, Wu F, Liu Y, Zheng Y, Zhang K, Siqin T, Liu M, Chen B, Wu J. Postoperative adjuvant treatment strategy for hepatocellular carcinoma with microvascular invasion: a non-randomized interventional clinical study. BMC Cancer 2020; 20:614. [PMID: 32611327 PMCID: PMC7329435 DOI: 10.1186/s12885-020-07087-7] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2020] [Accepted: 06/18/2020] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Microvascular invasion (MVI) is considered to be one of the important prognostic factors that affect postoperative recurrence in patients with hepatocellular carcinoma (HCC) with variable results across their treatment options. This study was carried out to investigate efficacy of postoperative adjuvant RT in HCC patients with MVI. METHODS This was single center, prospective study carried out in HCC patients with MVI, aged 35-72 years. All patients were non-randomly allocated to receive standard postoperative treatment of HBV/HCV and nutritional therapy or RT in addition to standard postoperative treatment (1:1). The primary endpoints assessed were relapse-free survival and overall survival. The prognostic factors associated with survival outcomes were also analyzed. The safety events were graded according to NCI-CTCAE v4.03 criteria. RESULTS Of the 115 patients eligible for study, 59 patients were included in analysis. Univariate analysis revealed that MVI classification (P = 0.009), post-operative treatment strategies (P = 0.009) were prognostic factors for worst RFS; tumor size (P = 0.011), MVI classification (P = 0.005) and post-operative treatment (P = 0.015) were associated for OS. The 1-, 2-, 3-year RFS rates were 86.2, 70.5 and 63.4% for patients in RT group, and 46.4, 36.1, and 36.1% in control group. For OS, corresponding rates were 96.6, 80.7, and 80.7% for patients in RT group and 79.7, 58.3, and 50.0% in control group. Subgroup classification of HCC patients according to low risk MVI showed significantly longer RFS (P = 0.035) and OS (P = 0.004) in RT group than control group, while for high risk MVI, RT depicted longer OS than control group with no significance (P = 0.106). Toxicities were usually observed in acute stage with no grade 4 toxicities. CONCLUSION Postoperative adjuvant RT following hepatectomy offers better RFS for HCC patients with MVI than with standard postoperative therapy. Also, it will be useful to control microscopic lesions in both M1 (low risk) and M2 (high risk) subgroups of HCC patients with MVI. TRIAL REGISTRATION Trial Registration number: ChiCTR1800017371 . Date of Registration: 2018-07-26. Registration Status: Retrospectively registered.
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Affiliation(s)
- Liming Wang
- Department of Hepatobiliary Surgery, National Cancer Center/ National Clinical Research Center for Cancer/ Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli Area, Chaoyang District, Beijing, 100021, China
| | - Weihu Wang
- Department of Radiation Oncology, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, 52 Fucheng Rd, Haidian District, Beijing, 100142, China
| | - Weiqi Rong
- Department of Hepatobiliary Surgery, National Cancer Center/ National Clinical Research Center for Cancer/ Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli Area, Chaoyang District, Beijing, 100021, China
| | - Zhuo Li
- Department of Pathology, National Cancer Center/ National Clinical Research Center for Cancer /Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli Area, Chaoyang District, Beijing, 100021, China
| | - Fan Wu
- Department of Hepatobiliary Surgery, National Cancer Center/ National Clinical Research Center for Cancer/ Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli Area, Chaoyang District, Beijing, 100021, China
| | - Yunhe Liu
- Department of Hepatobiliary Surgery, National Cancer Center/ National Clinical Research Center for Cancer/ Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli Area, Chaoyang District, Beijing, 100021, China
| | - Yiling Zheng
- Department of Hepatobiliary Surgery, National Cancer Center/ National Clinical Research Center for Cancer/ Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli Area, Chaoyang District, Beijing, 100021, China
| | - Kai Zhang
- Department of Hepatobiliary Surgery, National Cancer Center/ National Clinical Research Center for Cancer/ Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli Area, Chaoyang District, Beijing, 100021, China
| | - Tana Siqin
- Department of Hepatobiliary Surgery, National Cancer Center/ National Clinical Research Center for Cancer/ Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli Area, Chaoyang District, Beijing, 100021, China
| | - Mei Liu
- Laboratory of Cell and Molecular Biology & State Key Laboratory of Molecular Oncology, National Cancer Center/ National Clinical Research Center for Cancer /Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli Area, Chaoyang District, Beijing, 100021, China
| | - Bo Chen
- Department of Radiation Oncology, National Cancer Center/ National Clinical Research Center for Cancer /Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli Area, Chaoyang District, Beijing, 100021, China.
| | - Jianxiong Wu
- Department of Hepatobiliary Surgery, National Cancer Center/ National Clinical Research Center for Cancer/ Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli Area, Chaoyang District, Beijing, 100021, China.
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Hack SP, Spahn J, Chen M, Cheng AL, Kaseb A, Kudo M, Lee HC, Yopp A, Chow P, Qin S. IMbrave 050: a Phase III trial of atezolizumab plus bevacizumab in high-risk hepatocellular carcinoma after curative resection or ablation. Future Oncol 2020; 16:975-989. [PMID: 32352320 DOI: 10.2217/fon-2020-0162] [Citation(s) in RCA: 144] [Impact Index Per Article: 28.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023] Open
Abstract
Hepatocellular carcinoma recurs in 70-80% of cases following potentially curative resection or ablation and the immune component of the liver microenvironment plays a key role in recurrence. Many immunosuppressive mechanisms implicated in HCC recurrence are modulated by VEGF and/or immune checkpoints such as PD-L1. Atezolizumab (PD-L1 inhibitor) plus bevacizumab (VEGF inhibitor) has been shown to significantly improve overall survival, progression-free survival and overall response rate in unresectable HCC. Dual PD-L1/VEGF blockade may be effective in reducing HCC recurrence by creating a more immune-favorable microenvironment. We describe the rationale and design of IMbrave 050 (NCT04102098), a randomized, open-label, Phase III study comparing atezolizumab plus bevacizumab versus active surveillance in HCC patients at high-risk of recurrence following curative resection or ablation. The primary end point is recurrence-free survival. Clinical Trial Registration: NCT04102098.
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Affiliation(s)
- Stephen P Hack
- Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080, USA
| | - Jessica Spahn
- Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080, USA
| | - Minshan Chen
- Department of Hepatobiliary Surgery, Cancer Centre of Sun Yat-sen University, Guangzhou, PR China
| | - Ann-Lii Cheng
- National Taiwan University Cancer Center & National Taiwan University Hospital, Taipei, Taiwan
| | - Ahmed Kaseb
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Masatoshi Kudo
- Department of Gastroenterology & Hepatology, Kindai University School of Medicine, Osaka, Japan
| | - Han Chu Lee
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Adam Yopp
- Department of Surgery, Division of Surgical Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
| | - Pierce Chow
- Division of Surgical Oncology, National Cancer Centre, Singapore
| | - Shukui Qin
- PLA Cancer Center, People's Liberation Army (PLA) 81 Hospital, Nanjing 210016, PR China
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Zhang J, Qi YP, Ma N, Lu F, Gong WF, Chen B, Ma L, Zhong JH, Xiang BD, Li LQ. Overexpression of Epcam and CD133 Correlates with Poor Prognosis in Dual-phenotype Hepatocellular Carcinoma. J Cancer 2020; 11:3400-3406. [PMID: 32231746 PMCID: PMC7097958 DOI: 10.7150/jca.41090] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2019] [Accepted: 02/02/2020] [Indexed: 01/27/2023] Open
Abstract
Background: Dual-phenotype hepatocellular carcinoma (DPHCC) is associated with high rate of post-operative recurrence and low rate of survival, which may reflect the post-operative persistence of cancer stem cells (CSCs). Here we explored the potential correlation between DPHCC and expression of CSCs markers. Methods: In this retrospective study, we included 19 patients with DPHCC and 61 patients with non-DPHCC treated in 2015 by liver resection. Paraffin-embedded tumor tissue specimens were analyzed using immunohistochemistry as well as immunofluorescence double-staining. Rates of recurrence-free survival and overall survival were compared between the two groups using the Kaplan-Meier method, and expression of the CSC markers CD133, CD90, and EpCAM were compared using real-time quantitative PCR and western blotting. Results: Overall survival rates were significantly lower for patients with DPHCC than patients with non-DPHCC at 1 year (78.9% vs 93.4%), 2 years (52.6% vs 72.1%), and 3 years (42.1% vs 67.2%) (P = 0.019). Multivariate Cox proportional hazard modeling identified CK19 positivity (P = 0.016) and multiple nodules (P = 0.023) as independent predictors of poor recurrence-free survival. Independent predictors of poor overall survival were CK19 positivity (P = 0.032), Barcelona Clinic Liver Cancer stage C (P = 0.025) and carbohydrate antigen 19-9 (CA19-9) >37 ng/ml (P = 0.016). Expression of CD133 and EpCAM mRNA and protein were significantly higher in DPHCC tissue than non-DPHCC tissue, while CD90 expression was similar between the groups. Conclusions: These results suggest that DPHCC is associated with significantly lower overall survival than non-DPHCC, and that the poor prognosis among DPHCC patients may be related to the presence of CSCs expressing CD133 and EpCAM.
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Affiliation(s)
- Jie Zhang
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Guangxi, China
| | - Ya-Peng Qi
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Guangxi, China
| | - Ning Ma
- Graduate School of Health Science, Suzuka University of Medical Science, Suzuka, Japan
| | - Fei Lu
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Guangxi, China
| | - Weng-Feng Gong
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Guangxi, China
| | - Bin Chen
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Guangxi, China
| | - Liang Ma
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Guangxi, China
| | - Jian-Hong Zhong
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Guangxi, China
| | - Bang-De Xiang
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Guangxi, China
| | - Le-Qun Li
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Guangxi, China
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Development of a nomogram to predict outcome after liver resection for hepatocellular carcinoma in Child-Pugh B cirrhosis. J Hepatol 2020; 72:75-84. [PMID: 31499131 DOI: 10.1016/j.jhep.2019.08.032] [Citation(s) in RCA: 106] [Impact Index Per Article: 21.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2019] [Revised: 08/29/2019] [Accepted: 08/31/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS Treatment allocation in patients with hepatocellular carcinoma (HCC) on a background of Child-Pugh B (CP-B) cirrhosis is controversial. Liver resection has been proposed in small series with acceptable outcomes, but data are limited. The aim of this study was to evaluate the outcomes of patients undergoing liver resection for HCC in CP-B cirrhosis, focusing on the surgical risks and survival. METHODS Patients were retrospectively pooled from 14 international referral centers from 2002 to 2017. Postoperative and oncological outcomes were investigated. Prediction models for surgical risks, disease-free survival and overall survival were constructed. RESULTS A total of 253 patients were included, of whom 57.3% of patients had a preoperative platelet count <100,000/mm3, 43.5% had preoperative ascites, and 56.9% had portal hypertension. A minor hepatectomy was most commonly performed (84.6%) and 122 (48.2%) were operated on by minimally invasive surgery (MIS). Ninety-day mortality was 4.3% with 6 patients (2.3%) dying from liver failure. One hundred and eight patients (42.7%) experienced complications, of which the most common was ascites (37.5%). Patients undergoing major hepatectomies had higher 90-day mortality (10.3% vs. 3.3%; p = 0.04) and morbidity rates (69.2% vs. 37.9%; p <0.001). Patients undergoing an open hepatectomy had higher morbidity (52.7% vs. 31.9%; p = 0.001) than those undergoing MIS. A prediction model for surgical risk was constructed (https://childb.shinyapps.io/morbidity/). The 5-year overall survival rate was 47%, and 56.9% of patients experienced recurrence. Prediction models for overall survival (https://childb.shinyapps.io/survival/) and disease-free survival (https://childb.shinyapps.io/DFsurvival/) were constructed. CONCLUSIONS Liver resection should be considered for patients with HCC and CP-B cirrhosis after careful selection according to patient characteristics, tumor pattern and liver function, while aiming to minimize surgical stress. An estimation of the surgical risk and survival advantage may be helpful in treatment allocation, eventually improving postoperative morbidity and achieving safe oncological outcomes. LAY SUMMARY Liver resection for hepatocellular carcinoma in advanced cirrhosis (Child-Pugh B score) is associated with a high rate of postoperative complications. However, due to the limited therapeutic alternatives in this setting, recent studies have shown promising results after accurate patient selection. In our international multicenter study, we provide 3 clinical models to predict postoperative surgical risks and long-term survival following liver resection, with the aim of improving treatment allocation and eventually clinical outcomes.
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Wang L, Li Q, Zhang J, Lu J. A Novel Prognostic Scoring Model Based on Albumin and γ-Glutamyltransferase for Hepatocellular Carcinoma Prognosis. Cancer Manag Res 2019; 11:10685-10694. [PMID: 31920379 PMCID: PMC6934113 DOI: 10.2147/cmar.s232073] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2019] [Accepted: 11/15/2019] [Indexed: 01/27/2023] Open
Abstract
AIM To investigate the predictive value of albumin (ALB) and γ-glutamyltransferase (GGT) in hepatocellular carcinoma (HCC) patients undergoing curative resection. We sought to establish a new scoring model for predicting the prognosis of HCC patients undergoing curative resection. PATIENTS AND METHODS A retrospective analysis was performed in 303 HCC patients who underwent curative resection. Preoperative risk factors for survival were investigated using univariate and multivariate analyses. On the basis of significant factors, a prognostic scoring model was established. The overall survival (OS) and recurrence-free survival (RFS) were compared between different groups. RESULTS Multivariate Cox regression showed that preoperative decreased ALB levels and elevated GGT levels were significantly associated with poor OS and RFS. Multivariate analysis showed that ALB level, GGT level, portal vein tumor thrombus, and tumor number were independent prognostic factors for both OS and RFS. Thereafter, we established a preoperative prognostic scoring model combining the four risk factors. The results revealed that higher risk scores might mean worse OS and RFS. CONCLUSION Preoperative ALB and GGT levels are potentially useful biomarkers for predicting the prognostic outcomes in HCC patients undergoing curative resection. Our new prognostic scoring model qualifies as a novel prognostic predictor for HCC patients after curative resection.
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Affiliation(s)
- Liguang Wang
- Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong250021, People’s Republic of China
| | - Qun Li
- Department of Infectious Disease, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong250021, People’s Republic of China
| | - Jie Zhang
- Department of Infectious Disease, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong250021, People’s Republic of China
| | - Jun Lu
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong250021, People’s Republic of China
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Liu J, Xie S, Duan X, Chen J, Zhou X, Li Y, Li Z, Han X. Assessment of efficacy and safety of the transcatheter arterial chemoembolization with or without apatinib in the treatment of large hepatocellular carcinoma. Cancer Chemother Pharmacol 2019; 85:69-76. [PMID: 31813003 DOI: 10.1007/s00280-019-04004-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2019] [Accepted: 11/26/2019] [Indexed: 02/06/2023]
Abstract
PURPOSE The goal of this study was to assess the clinical efficacy and safety of the transcatheter arterial chemoembolization (TACE) in combination with apatinib or TACE treatment alone in patients with large hepatocellular carcinoma (HCC). METHODS A total of 82 patients with large HCC were consecutively enrolled between January 2016 and December 2017. Of the 82 patients, 34 underwent the combined treatment, while 48 underwent TACE alone. The treatment response was assessed at first month and third month after TACE therapy, and the survival rate at median follow-up time was also compared between the two treatment groups. Furthermore, progression-free survival (PFS), overall survival (OS) and treatment-related complications were assessed and compared. RESULTS Patients treated with TACE + apatinib presented with better objective response rate and disease control rate compared to those who only underwent TACE. Median OS as well as median PFS was longer in the TACE plus apatinib group compared to the TACE alone group. Multivariate Cox's regression analysis further illustrated that TACE plus apatinib compared to TACE alone was an independent protective factor for PFS and OS. CONCLUSION TACE combined with apatinib is a safe and promising treatment approach for patients with large HCC.
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Affiliation(s)
- Juanfang Liu
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, No. 1, East Jian She Road, Zhengzhou, 450052, Henan, People's Republic of China
| | - Shanshan Xie
- Department of Magnetic Resonance Imaging, The First Affiliated Hospital of Zhengzhou University, No. 1, East Jian She Road, Zhengzhou, 450052, Henan, People's Republic of China
| | - Xuhua Duan
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, No. 1, East Jian She Road, Zhengzhou, 450052, Henan, People's Republic of China.,Department of Magnetic Resonance Imaging, The First Affiliated Hospital of Zhengzhou University, No. 1, East Jian She Road, Zhengzhou, 450052, Henan, People's Republic of China
| | - Jianjian Chen
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, No. 1, East Jian She Road, Zhengzhou, 450052, Henan, People's Republic of China
| | | | - Yahua Li
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, No. 1, East Jian She Road, Zhengzhou, 450052, Henan, People's Republic of China
| | - Zhaonan Li
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, No. 1, East Jian She Road, Zhengzhou, 450052, Henan, People's Republic of China
| | - Xinwei Han
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, No. 1, East Jian She Road, Zhengzhou, 450052, Henan, People's Republic of China.
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Luo Y, Fu HY, Huang HL, Li HJ, Zhang J, Zhou YJ, Xu B, Wang J. Transcatheter arterial chemoembolization combined with microwave ablation for treatment of early liver cancer: Efficacy and prognostic factors for progression-free survival. Shijie Huaren Xiaohua Zazhi 2019; 27:1201-1208. [DOI: 10.11569/wcjd.v27.i19.1201] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Transcatheter arterial chemoembolization (TACE) and microwave ablation (MWA) are the main methods for the treatment of liver cancer worldwide. TACE can block the blood vessels of liver cancer and clearly show the area where the tumor is located. The solid tumor can be completely ablated by MWA. However, postoperative recurrence is still a difficult problem to solve.
AIM To assess the efficacy of TACE combined with MWA in the treatment of liver cancer at early Barcelona clinic liver cancer (BCLC) stage and identify the factors affecting recurrence.
METHODS A retrospective analysis was performed on 42 patients with post-hepatitis B virus (HBV) liver cancer at early BCLC stage who underwent TACE combined with MWA at our hospital from February 2016 to November 2017. After surgery, the efficacy was evaluated and complications were recorded. The patients were followed at 1 mo, 2 mo, 3, mo 6 mo, 12 mo, and 18 mo after WMA for CT, alpha fetoprotein (AFP), liver function, or hepatic angiography, and the time to recurrence was recorded.
RESULTS By the last follow-up, the total effective rate was 61.5% and the lesion control rate was 84.2%. The median progression-free-survival (PFS) was 7.3 mo (range, 2.3-34). Univariate analysis showed that female patients had a PFS of 14 mo and male patients had a PFS of 11 mo. Patients ≥ 60 years of age had a PFS of 3.8 mo, and patients < 60 years of age had a PFS of 8.9 mo. The PFS of patients with tumor < 3 cm, 3 to 5 cm, and 5-10 cm was 14, 10.5, and 11.2 mo, respectively. The PFS of patients with single tumor and multiple tumors was 13.6 and 4 mo, respectively. The PFS of patients with Child A and Child B disease was 20.8 mo vs 11.2 mo. The PFS of BCLC stage 0 patients and BCLC stage A patients was 15.5 mo vs 11.2 mo. HBV-DNA positive patients had a PFS of 11.2 mo, and HBV-DNA negative patients had a PFS of 13.3 mo. The median PFS of HBeAg-positive cases was 11.2 mo, and that of HBeAg-negative cases was 13.3 mo. Univariate analysis showed that gender, age, Child grade, number of tumors, and BCLC stage were significantly correlated with PFS, but tumor size, preoperative HBV-DNA, and HBeAg status did not. In multivariate analysis, Child grade, BCLC stage, and gender were identified to be independent risk factors for PFS in early BCLC stage liver cancer patients undergoing sequential treatment of TACE and MWA (P < 0.05).
CONCLUSION TACE combined with MWA is safe and effective in the treatment of early BCLC stage liver cancer. Child grade, BCLC stage, and gender may affect postoperative recurrence.
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Affiliation(s)
- Yu Luo
- Department of Cancer Intervention, the 3rd People's Hospital of Kunming, Kunming 650200, Yunnan Province, China
| | - Hai-Yan Fu
- Department of Cancer Intervention, the 3rd People's Hospital of Kunming, Kunming 650200, Yunnan Province, China
| | - Hong-Li Huang
- Department of Cancer Intervention, the 3rd People's Hospital of Kunming, Kunming 650200, Yunnan Province, China
| | - Hong-Juan Li
- Department of Cancer Intervention, the 3rd People's Hospital of Kunming, Kunming 650200, Yunnan Province, China
| | - Jie Zhang
- Department of Cancer Intervention, the 3rd People's Hospital of Kunming, Kunming 650200, Yunnan Province, China
| | - Yu-Jun Zhou
- Department of Cancer Intervention, the 3rd People's Hospital of Kunming, Kunming 650200, Yunnan Province, China
| | - Bin Xu
- Department of Cancer Intervention, the 3rd People's Hospital of Kunming, Kunming 650200, Yunnan Province, China
| | - Jie Wang
- Department of Cancer Intervention, the 3rd People's Hospital of Kunming, Kunming 650200, Yunnan Province, China
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Cerrito L, Annicchiarico BE, Iezzi R, Gasbarrini A, Pompili M, Ponziani FR. Treatment of hepatocellular carcinoma in patients with portal vein tumor thrombosis: Beyond the known frontiers. World J Gastroenterol 2019; 25:4360-4382. [PMID: 31496618 PMCID: PMC6710186 DOI: 10.3748/wjg.v25.i31.4360] [Citation(s) in RCA: 70] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2019] [Revised: 06/24/2019] [Accepted: 07/19/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma is one of the most frequent malignant tumors worldwide: Portal vein tumor thrombosis (PVTT) occurs in about 35%-50% of patients and represents a strong negative prognostic factor, due to the increased risk of tumor spread into the bloodstream, leading to a high recurrence risk. For this reason, it is a contraindication to liver transplantation and in several prognostic scores sorafenib represents its standard of care, due to its antiangiogenetic action, although it can grant only a poor prolongation of life expectancy. Recent scientific evidences lead to consider PVTT as a complex anatomical and clinical condition, including a wide range of patients with different prognosis and new treatment possibilities according to the degree of portal system involvement, tumor biological aggressiveness, complications caused by portal hypertension, patient's clinical features and tolerance to antineoplastic treatments. The median survival has been reported to range between 2.7 and 4 mo in absence of therapy, but it can vary from 5 mo to 5 years, thus depicting an extremely variable scenario. For this reason, it is extremely important to focus on the most adequate strategy to be applied to each group of PVTT patients.
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MESH Headings
- Antineoplastic Combined Chemotherapy Protocols/therapeutic use
- Carcinoma, Hepatocellular/complications
- Carcinoma, Hepatocellular/mortality
- Carcinoma, Hepatocellular/therapy
- Chemoembolization, Therapeutic/methods
- Contrast Media/administration & dosage
- Disease-Free Survival
- Hepatectomy
- Humans
- Hypertension, Portal/etiology
- Hypertension, Portal/mortality
- Hypertension, Portal/therapy
- Liver Neoplasms/complications
- Liver Neoplasms/mortality
- Liver Neoplasms/therapy
- Liver Transplantation
- Neoadjuvant Therapy/methods
- Neoplasm Invasiveness/pathology
- Neoplasm Recurrence, Local/epidemiology
- Neoplasm Recurrence, Local/pathology
- Neoplasm Recurrence, Local/prevention & control
- Patient Selection
- Portal Vein/diagnostic imaging
- Portal Vein/pathology
- Prognosis
- Survival Analysis
- Thrombectomy
- Time Factors
- Ultrasonography/methods
- Venous Thrombosis/etiology
- Venous Thrombosis/mortality
- Venous Thrombosis/therapy
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Affiliation(s)
- Lucia Cerrito
- Division of Internal Medicine, Gastroenterology and Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Brigida Eleonora Annicchiarico
- Division of Internal Medicine, Gastroenterology and Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Roberto Iezzi
- Department of Bioimaging and Radiological Sciences, Institute of Radiology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Antonio Gasbarrini
- Division of Internal Medicine, Gastroenterology and Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Maurizio Pompili
- Division of Internal Medicine, Gastroenterology and Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Francesca Romana Ponziani
- Division of Internal Medicine, Gastroenterology and Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
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Jang TY, Huang CI, Yeh ML, Lin ZY, Chen SC, Chuang WL. The prognosis of bulky hepatocellular carcinoma with nonmajor branch portal vein tumor thrombosis. Medicine (Baltimore) 2019; 98:e15066. [PMID: 30921239 PMCID: PMC6455711 DOI: 10.1097/md.0000000000015066] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
A bulky, solitary hepatocellular carcinoma (HCC) with nonmajor branch portal vein tumor thrombosis (PVTT) was staged as T2 in the tumor-node-metastasis (TNM) system. We aimed to evaluate the prognosis of this group of patients.A total of 2643 patients with HCC in a medical center were consecutively enrolled. The stage of HCC was determined according to the 7th edition of American Joint Committee on Cancer staging system. Patients who were diagnosed as having solitary HCC larger than 5 cm with nonmajor portal vein thrombosis (VP1-VP2) and no lymphadenopathy or metastasis were included.Bulky HCC with nonmajor branch PVTT and without metastasis and lymphadenopathy was identified in 0.15% (4 out of 2643 patients) of the patients with HCC. Child-Pugh scores of the patients were A to B. Tumor sizes all were larger than 5 cm (mean: 6.8 ± 1.0 cm). All patients had nonmajor branch of PVTT. Three patients initially received trans-arterial chemoembolization (TACE) therapy, and 1 patient refused treatment because of old age. The response to TACE was poor: 2 patients rapidly progressed to main portal vein thrombosis, and their tumors enlarged within a half year. Only 1 patient's disease remained stable but progressed gradually 2 years later. The median survival time was 16.5 months. The 1- year, 2-year, and 3-year survival rate was 100%, 50%, and 0%, respectively.Solitary HCC > 5 cm with PVTT of a nonmajor branch gave dismal prognoses and required aggressive treatment such as hepatic resection or combination therapy. In our opinion, it should be staged as T3 rather than a T2 in the TNM staging system.
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Affiliation(s)
- Tyng-Yuan Jang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung
- Department of Internal Medicine, Pingtung Hospital, Ministry of Health and Welfare, Pingtung
| | - Ching-I. Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Zu-Yau Lin
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Shinn-Cherng Chen
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
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Solaini L, Cucchetti A, Piccino M, Gardini A, La Barba G, Serenari M, Cescon M, Ercolani G. Critical systematic review on hepatic resection and transarterial chemoembolization for hepatocellular carcinoma. Future Oncol 2019; 15:439-449. [PMID: 30620230 DOI: 10.2217/fon-2018-0269] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
Whether to submit to transarterial chemoembolization (TACE) or hepatic resection (HR) patients with hepatocellular carcinoma (HCC) is still a debated issue. We conducted a systematic review to critically analyze what evidence supports the use of TACE, in a specific clinical condition that can define HCC as 'intermediate'. In addition, we analyzed literature regarding the comparison between TACE and HR. Direct comparisons, between HR and TACE, strongly support the adoption of surgery for patients with large or multinodular HCCs since, albeit 'nonideal' surgical candidates, these patients can still obtain a survival benefit. Multidisciplinary teams can mitigate the different decision-making approach of surgeons and hepatologists with the aim of obtaining the best quality of care.
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Affiliation(s)
- Leonardo Solaini
- General and Oncology Surgery, Morgagni-Pierantoni Hospital, Forli, 47121, Italy.,Department of Medical & Surgical Sciences - DIMEC, Alma Mater Studiorum - University of Bologna, Bologna, 40138, Italy
| | - Alessandro Cucchetti
- General and Oncology Surgery, Morgagni-Pierantoni Hospital, Forli, 47121, Italy.,Department of Medical & Surgical Sciences - DIMEC, Alma Mater Studiorum - University of Bologna, Bologna, 40138, Italy
| | - Marco Piccino
- Division of General & Hepatobiliary Surgery, Department of Surgery, University of Verona Medical School, Verona, 37134, Italy
| | - Andrea Gardini
- General and Oncology Surgery, Morgagni-Pierantoni Hospital, Forli, 47121, Italy
| | - Giuliano La Barba
- General and Oncology Surgery, Morgagni-Pierantoni Hospital, Forli, 47121, Italy
| | - Matteo Serenari
- Department of Medical & Surgical Sciences - DIMEC, Alma Mater Studiorum - University of Bologna, Bologna, 40138, Italy
| | - Matteo Cescon
- Department of Medical & Surgical Sciences - DIMEC, Alma Mater Studiorum - University of Bologna, Bologna, 40138, Italy
| | - Giorgio Ercolani
- General and Oncology Surgery, Morgagni-Pierantoni Hospital, Forli, 47121, Italy.,Department of Medical & Surgical Sciences - DIMEC, Alma Mater Studiorum - University of Bologna, Bologna, 40138, Italy
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Zhang XP, Gao YZ, Chen ZH, Wang K, Cheng YQ, Guo WX, Shi J, Zhong CQ, Zhang F, Cheng SQ. In-hospital Mortality after Surgical Resection in Hepatocellular Carcinoma Patients with Portal Vein Tumor Thrombus. J Cancer 2019; 10:72-80. [PMID: 30662527 PMCID: PMC6329847 DOI: 10.7150/jca.27102] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2018] [Accepted: 10/03/2018] [Indexed: 02/07/2023] Open
Abstract
Background: Survival benefit of surgical resection for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) has been approved recently. However, risk factors for in-hospital mortality in these patients remain unclear. We aimed to determine risk factors and reduce the mortality of these patients. Methods: We analyzed data for 521 of all 1531 HCC patients with PVTT underwent surgery. The primary outcome measure was in-hospital mortality after surgical resection. Univariate and Multivariate cox-regression were performed to identify independent predictors of in-hospital mortality. The methods of Kaplan-Meier, bootstrap and ten-fold-cross validation were applied to validate the risk factors. Results: 521 of 1531 patients in 2004-2012 occurred for the diagnosis of HCC associated with PVTT and underwent surgical resection as a training cohort. Other 325 patients in 2013-2016 were included as a validation cohort. Overall mortality of postoperative in-patients was 3.3% (17/521) and 2.8 % (9/325), respectively. Univariate analysis of mortality revealed that frequency of hospitalization, total albumin, different types of PVTT, bleeding volume, blood transfusion, resection volume, and tumor volume were related with mortality. Therefore, the bootstrap validation reflected that the risk factors of multivariate cox regression in model1(frequency of hospitalization, bleeding volume, and tumor volume) and model 2 (frequency of hospitalization, bleeding volume and total albumin) were stable with mortality in hospital. Ten-fold cross-validation of cox regression analysis showed that the mean C-statistic with 95%CI of model1 and model2 respectively were 0.887(0.779-0.976) and 0.867(0.789-0.966) for predicting in-hospital mortality. Consistency results of models were in the training cohort and validation cohort. Conclusion: Total albumin, tumor volume, intraoperative bleeding and frequency of hospitalization were independent predictive factors for in-hospital mortality in HCC patients with PVTT under surgery. Further study is warranted to utilize these factors to lower in-hospital mortality.
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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 School, Yangzhou University, Yangzhou, China
| | - Zhen-Hua Chen
- 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
| | - Yu-Qiang Cheng
- 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
| | - Cheng-Qian Zhong
- LongYan First Hospital, Affiliated to Fujian Medical University, FuJian, China
| | - Fan Zhang
- Department of Hepatic Surgery, BinZhou medical University Hospital, BinZhou, China
| | - Shu-Qun Cheng
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University. Shanghai, China
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Zhao LY, Huo RR, Xiang X, Torzilli G, Zheng MH, Yang T, Liang XM, Huang X, Tang PL, Xiang BD, Li LQ, You XM, Zhong JH. Hepatic resection for elderly patients with hepatocellular carcinoma: a systematic review of more than 17,000 patients. Expert Rev Gastroenterol Hepatol 2018; 12:1059-1068. [PMID: 30145919 DOI: 10.1080/17474124.2018.1517045] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND With the aging population and increasing incidence of hepatic malignancies in elderly patients, establishing the safety and efficacy of hepatic resection for elderly patients with hepatocellular carcinoma (HCC) is crucial. The present systematic review investigates postoperative morbidity, hospital mortality, median survival time, overall and disease-free survival in elderly patients with undergoing hepatic resection. METHODS Some databases were systematically searched for prospective or retrospective studies to reveal the safety and efficacy of hepatic resection for elderly patients with primary HCC. RESULTS Fifty studies involving 4,169 elderly patients and 13,158 young patients with HCC were included into analyses. Elderly group patients had similar rate of median postoperative morbidity (28.2% vs. 29.6%) but higher mortality (3.0% vs. 1.2%) with young group patients. Moreover, elderly group patients had slightly lower median survival time (55 vs. 58 months), 5-years overall survival (51% vs. 56%) and 5-years disease-free survival (27% vs. 28%) than young group patients. There was an upward trend in 5-years overall and disease-free survival in either elderly or young group. CONCLUSION Though old age may increase the risk of hospital mortality for patients with HCC after hepatic resection, elderly patients can obtain acceptable long-term prognoses from hepatic resection.
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Affiliation(s)
- Ling-Yun Zhao
- a Hepatobiliary Surgery Department , Affiliated Tumor Hospital of Guangxi Medical University , Nanning , China
| | - Rong-Rui Huo
- a Hepatobiliary Surgery Department , Affiliated Tumor Hospital of Guangxi Medical University , Nanning , China
| | - Xiao Xiang
- a Hepatobiliary Surgery Department , Affiliated Tumor Hospital of Guangxi Medical University , Nanning , China
| | - Guido Torzilli
- b Department of Surgery, Division of Hepatobiliary and General Surgery , Humanitas University, Humanitas Research Hospital-IRCCS , Rozzano, Milan , Italy
| | - Ming-Hua Zheng
- c Department of Hepatology , Liver Research Center, the First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China
| | - Tian Yang
- d Department of Hepatobiliary Surgery , Eastern Hepatobiliary Surgery Hospital, Second Military Medical University , Shanghai , China
| | - Xin-Min Liang
- e Grade 2016 , Basic medical college of Guangxi Medical University , Nanning , China
| | - Xi Huang
- e Grade 2016 , Basic medical college of Guangxi Medical University , Nanning , China
| | - Pei-Ling Tang
- e Grade 2016 , Basic medical college of Guangxi Medical University , Nanning , China
| | - Bang-De Xiang
- a Hepatobiliary Surgery Department , Affiliated Tumor Hospital of Guangxi Medical University , Nanning , China.,f Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center , Nanning , China
| | - Le-Qun Li
- a Hepatobiliary Surgery Department , Affiliated Tumor Hospital of Guangxi Medical University , Nanning , China.,f Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center , Nanning , China
| | - Xue-Mei You
- a Hepatobiliary Surgery Department , Affiliated Tumor Hospital of Guangxi Medical University , Nanning , China.,f Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center , Nanning , China
| | - Jian-Hong Zhong
- a Hepatobiliary Surgery Department , Affiliated Tumor Hospital of Guangxi Medical University , Nanning , China.,f Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center , Nanning , China
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Lalisang TJ, Moenadjat Y, Siregar NC, Stephanie M. Overexpression of p53 in extra large (more than 10 cm) hepatocellular carcinoma. MEDICAL JOURNAL OF INDONESIA 2018. [DOI: 10.13181/mji.v27i2.1980] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Background: Extra large hepatocellular carcinoma (HCC) of >10 cm managed in our center shows a specific characteristic in tropical regions. This type of HCC exhibits distinct p53 expression. This study aimed to determine the association between p53 expression and tumor size and behavior. Method: Subjects with HCC who underwent surgical resection in our hospital during 2012–2015 were enrolled in thisstudy. Subject’s characteristics, tumor size, histopathology findings, and tumor behavior were variables observed. Animmunohistochemical study on p53 expression was conducted to determine its association with those variables.Results: This study involved 38 subjects with tumor size ranging from 3 cm to 25 cm in diameter and 20 subjects (52.8%) with tumor size ranging from 10 cm to 25 cm in diameter. Only 13 samples were evaluated for p53 expression. Five subjects with >10 cm (extra large) tumor showed highly/overexpressed p53 (intensity>50%), two subjects with strong p53 expression (intensity>5%–50%), and two subjects with weak expression. Three subjects with <10 cm (large) tumor showed strong expression of p53 (5%–9%) and a subject with 3 cm tumor showed weak p53 expression (<5%). Highly expressed p53 was found in patients with microvascular invasion, inflammatory response, mitosis, and necrosis.Conclusion: Overexpression of p53 was associated with extra large and poorly differentiated HCC.
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Jiang Y, Tang H, Wang Z, Sun Y, Meng W, Wang G, Li H, Yi S, Wang G, Yang Y, Chen G. Two Nomograms to Select Hepatocellular Carcinoma Patients with Macroscopic Vascular Invasion for Hepatic Resection. J Cancer 2018; 9:3287-3294. [PMID: 30271488 PMCID: PMC6160689 DOI: 10.7150/jca.25899] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2018] [Accepted: 07/17/2018] [Indexed: 01/27/2023] Open
Abstract
Background: Hepatocellular carcinoma (HCC) patients with macroscopic vascular invasion (MaVI) have limited lifespans. According to recent studies, surgical treatment may be the most promising option. However, the current staging system does not select patients who will benefit most from hepatic resection. Study design: A total of 123 patients undergoing hepatic resection for HCC with macroscopic vascular invasion (MaVI) between 2010 and 2014 at The Third Affiliated Hospital of Sun Yat-sen University were selected. We developed nomograms for overall survival (OS) and recurrence-free survival (RFS) using a Cox proportional hazards model. We assessed nomogram model performance based on the concordance index (C-index) and a calibration plot. Results: The 1- and 3-year overall survival (OS) rates for all patients were 84% and 71%, respectively. Correspondingly, the 1- and 3-year recurrence-free survival (RFS) rates were 55% and 35%, respectively. In the multivariate Cox model, the extent of vascular invasion, tumour count, fibrinogen, HBV DNA load and serum potassium significantly affected prognosis. The C-index of the two nomograms were 0.80 and 0.69 for OS and RFS respectively. Based on our nomogram, patients predicted to have 1-year and 3-year RFS rates of more than 80% and 56% had actual 1-year and 3-year RFS rates of 81.8% and 57.1%, respectively, including 9.0% and 17.1% of the HCC patients with MaVI in our database. Conclusion: Surgical treatments are a therapeutic option that can provide more survival benefit for HCC patients with MaVI. With the help of our nomograms, selected HCC patients with MaVI can benefit from hepatic resection and have the same survival rate as that for early-stage HCC patients.
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Affiliation(s)
- Yiquan Jiang
- Department of Hepatic Surgery and Liver Transplantation Center of the Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-sen University; Organ Transplantation Research Center of Guangdong Province
| | - Hui Tang
- Key Laboratory of Liver Disease Research of Guangdong Province, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Zixian Wang
- Department of Medical Oncology, Sun Yat-Sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou 510060, China
| | - Yuanjing Sun
- Department of Hepatic Surgery and Liver Transplantation Center of the Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-sen University; Organ Transplantation Research Center of Guangdong Province
| | - Wei Meng
- Department of Hepatic Surgery and Liver Transplantation Center of the Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-sen University; Organ Transplantation Research Center of Guangdong Province
| | - Guoying Wang
- Department of Hepatic Surgery and Liver Transplantation Center of the Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-sen University; Organ Transplantation Research Center of Guangdong Province
| | - Hua Li
- Department of Hepatic Surgery and Liver Transplantation Center of the Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-sen University; Organ Transplantation Research Center of Guangdong Province
| | - Shuhong Yi
- Department of Hepatic Surgery and Liver Transplantation Center of the Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-sen University; Organ Transplantation Research Center of Guangdong Province
| | - Genshu Wang
- Department of Hepatic Surgery and Liver Transplantation Center of the Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-sen University; Organ Transplantation Research Center of Guangdong Province
| | - Yang Yang
- Department of Hepatic Surgery and Liver Transplantation Center of the Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-sen University; Organ Transplantation Research Center of Guangdong Province.,Key Laboratory of Liver Disease Research of Guangdong Province, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Guihua Chen
- Department of Hepatic Surgery and Liver Transplantation Center of the Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-sen University; Organ Transplantation Research Center of Guangdong Province.,Key Laboratory of Liver Disease Research of Guangdong Province, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
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Hyun MH, Lee YS, Kim JH, Lee CU, Jung YK, Seo YS, Yim HJ, Yeon JE, Byun KS. Hepatic resection compared to chemoembolization in intermediate- to advanced-stage hepatocellular carcinoma: A meta-analysis of high-quality studies. Hepatology 2018; 68:977-993. [PMID: 29543988 DOI: 10.1002/hep.29883] [Citation(s) in RCA: 145] [Impact Index Per Article: 20.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2017] [Revised: 12/21/2017] [Accepted: 02/28/2018] [Indexed: 01/27/2023]
Abstract
UNLABELLED According to the American Association for the Study of Liver Diseases (AASLD) treatment guidelines for hepatocellular carcinoma (HCC), the role of surgery has been expanded beyond the Barcelona Clinic Liver Cancer (BCLC) algorithm. We compared primary hepatectomy (PH) with transarterial chemoembolization (TACE) in patients with intermediate- to advanced-stage (BCLC stage B/C) HCC to determine the current evidence. Through a database search, we included 18 high-quality studies (one randomized controlled trial [RCT], five propensity-score matching nonrandomized comparative trials [NRCTs], and 12 NRCTs) that compared survival outcomes of 5,986 patients after PH and TACE. We found significant survival benefits for PH over TACE in BCLC stage B/C patients (hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.51-0.67; P < 0.00001; I2 = 84%). According to the BCLC, both stage B and stage C patients showed significantly better overall survival (OS) for PH compared to TACE (HR, 0.53; 95% CI, 0.43-0.65; P < 0.00001; I2 = 77%; HR, 0.67; 95% CI, 0.59-0.77; P < 0.00001; I2 = 79%, respectively). Five-year survival rates for PH were significantly higher than those for TACE in BCLC stage B/C, stage B, and BCLC stage C patients (odds ratio [OR], 2.71, 2.77, and 3.03, respectively; all P < 0.00001). Survival benefits persisted across subgroup, sensitivity, and metaregression analyses; interstudy heterogeneity remained constant. CONCLUSION This meta-analysis suggests that surgical resection provides survival benefits in patients with intermediate- to advanced-stage HCC. The evidence found herein may assist in the choice of treatment modality based on diverse definitions of operability. (Hepatology 2018).
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Affiliation(s)
- Myung Han Hyun
- Division of Oncology and Hematology, Department of Internal Medicine, Korea University Medical Center, Seoul, Korea
| | - Young-Sun Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Medical Center, Seoul, Korea
| | - Ji Hoon Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Medical Center, Seoul, Korea
| | - Chan Uk Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Medical Center, Seoul, Korea
| | - Young Kul Jung
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Medical Center, Seoul, Korea
| | - Yeon Seok Seo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Medical Center, Seoul, Korea
| | - Hyung Joon Yim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Medical Center, Seoul, Korea
| | - Jong Eun Yeon
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Medical Center, Seoul, Korea
| | - Kwan Soo Byun
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Medical Center, Seoul, Korea
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Adjuvant transarterial chemoembolization for patients with hepatocellular carcinoma involving microvascular invasion. Am J Surg 2018; 217:739-744. [PMID: 30103903 DOI: 10.1016/j.amjsurg.2018.07.054] [Citation(s) in RCA: 52] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2018] [Revised: 07/06/2018] [Accepted: 07/12/2018] [Indexed: 01/27/2023]
Abstract
BACKGROUND Microvascular invasion (MVI) has recently been reported to be an independent prognostic factor in patients with hepatocellular carcinoma (HCC). This study compared the outcomes of adjuvant transarterial chemoembolization (A-TACE) after hepatic resection (HR) in patients with HCC involving MVI. METHODS This prospective study involved 200 consecutive patients with MVI-HCC who underwent HR alone (n = 109) or HR with A-TACE (n = 91).The Kaplan-Meier method was used to compare disease-free survival (DFS) and overall survival (OS). RESULTS The two groups showed similar DFS at 1, 2, and 3 years (P = 0.077). The A-TACE group showed significantly higher OS than the HR-only group (P = 0.030). Subgroup analysis showed that A-TACE was associated with significantly higher DFS and OS among patients with a tumor diameter >5 cm or with multinodular tumors. CONCLUSIONS A-TACE may improve postoperative outcomes for MVI-HCC patients, especially those with tumor diameter >5 cm or multinodular tumors.
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Xu W, Rao Q, An Y, Li M, Xu G, Sang X, Lu X, Zhang Z, Mao Y. Proposal for subclassification to select patients for hepatectomy with intermediate hepatocellular carcinoma and Child-Pugh A liver function: A double-center study from China. Medicine (Baltimore) 2018; 97:e11800. [PMID: 30095644 PMCID: PMC6133538 DOI: 10.1097/md.0000000000011800] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/27/2023] Open
Abstract
Increasing evidence has shown that hepatectomy provides a longer overall survival (OS) for patients with hepatocellular carcinoma (HCC) in the intermediate stage. Unfortunately, not all patients benefit from liver resection, even if hepatectomy is feasible. This study aimed to propose a subclassification to select patients for surgical resection.OS of patients with intermediate-stage HCC who underwent hepatectomy at Beijing Friendship Hospital or Peking Union Medical College Hospital were reviewed. Patients were divided into 2 groups based on the results of survival analysis. The prognosis of these patients was compared with that in those who were treated by trans-arterial chemoembolization (TACE) in each subgroup.A total of 259 patients with intermediate-stage HCC who were initially treated by hepatectomy were included. Multivariate analysis showed that cumulative tumor size and tumor number independently affected tumor recurrence and survival time of these patients. Patients were then divided into group A (tumor size <11 cm and tumor number < 4; n = 205) and group B (tumor size ≥11 cm and tumor number ≥ 4; n = 54). Multivariate analysis showed that hepatectomy was independently associated with longer OS compared with TACE in patients in group A (hazard ratio = 0.67, 95% confidence interval = 0.49-0.90), but not in group B.Surgical management of intermediate-stage HCC should be performed with more complexity than current practice. Hepatic resection could be considered as the first-line treatment only for patients with HCC who have a cumulative tumor size of less than 11 cm and <4 tumors.
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Affiliation(s)
- Wei Xu
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Cancer Invasion and Metastasis Research, National Clinical Research Center for Digestive Diseases Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China
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Tissue miRNA 483-3p expression predicts tumor recurrence after surgical resection in histologically advanced hepatocellular carcinomas. Oncotarget 2018; 9:17895-17905. [PMID: 29707155 PMCID: PMC5915163 DOI: 10.18632/oncotarget.24860] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2017] [Accepted: 02/27/2018] [Indexed: 02/07/2023] Open
Abstract
The choice of surgical treatment for hepatocellular carcinoma (HCC) depends on several prognostic variables, among which histological features, like microvascular invasion and tumor grade, are well established. This study aims to identify the tissue miRNAs predictive of recurrence after liver resection in "histologically advanced" HCC. We selected 54 patients: 15 retrospective resected patients without recurrence (group A), 19 retrospective resected patients with HCC recurrence (group B), and 20 prospective patients (group C), with 4 recurrence cases. All selected HCC were "histologically advanced" (high Edmondson grade and/or presence of microvascular invasion). A wide spectrum of miRNAs was studied with TaqMan Human microRNA Arrays; qRT-PCR assays were used to validate results on selected miRNAs; immunohistochemistry for IGF2 was applied to study the mechanism of miR-483-3p. As a result, a significant differential expression between group A and B was found for 255 miRNAs. Among them we selected miR-483-3p and miR-548e (P<0.001). As a single variable (group C), HCC with miR-483-3p downregulation (mean fold increase 0.21) had 44.4% of recurrence cases; HCC with miR-483-3p upregulation (mean fold increase 5.94) showed no recurrence cases (P=0.011). At immunohistochemistry (group C), the HCC with loss of cytoplasmic IGF2 expression showed a down-regulation of miR-483-3p (fold increase 0.57). In conclusion, in patients with "histologically advanced" HCC, the analysis of specific tissue miRNAs (particularly miR-483-3p) could help identify the recurrence risk and choose which treatment algorithm to implement (follow-up, resection or transplantation). This could have an important impact on patient survival and transplantation outcome, improving organ allocation.
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Zhang J, Li H, Gao D, Zhang B, Zheng M, Lun M, Wei M, Duan R, Guo M, Hua J, Liu Q, Bai J, Liu H, Zheng J, Yao H. A prognosis and impact factor analysis of DC-CIK cell therapy for patients with hepatocellular carcinoma undergoing postoperative TACE. Cancer Biol Ther 2018; 19:475-483. [PMID: 29400599 DOI: 10.1080/15384047.2018.1433501] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
Dendritic cell-cytokine-induced killer (DC-CIK) cell therapy has been experimentally implemented for enhancing anti-tumoral immunity in patients with hepatocellular carcinoma (HCC) undergoing postoperative transcatheter arterial chemoembolization (POTACE). We performed a retrospective study to evaluate the clinical efficacies of DC-CIK cell therapy and its correlations with several immune factors of the primary tumors. The overall survival time of HCC patients with HBV infection in the study group (POTACE plus DC-CIK cell therapy) was significantly longer than that of the control group (POTACE alone). The expression level of PD-L1 but not the tumor-infiltrated CD8 and CD4 T cells in the tumor tissues showed significant negative correlations with relapse-free survival (RFS) and overall survival (OS), which was also an independent prognostic factor for the five-years' suvival of patients with HCC receiving POTACE treatment. Furthermore, our study validated that PD-L1 expression was significantly inversely correlated with the survival time of HCC patients receiving POTACE plus DC-CIK cell therapy treatment. More importantly, DC-CIK cell therapy provided the best clinical benefits to HCC patients with the low PD-L1 expression receiving POTACE, which indicate that PD-L1 expression level can serve as a pivotal predictor for the therapeutic efficacy of DC-CIK cell therapy for HCC patients receiving POTACE treatment.
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Affiliation(s)
- Jian Zhang
- a Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University , Xuzhou , Jiangsu , China
| | - Huizhong Li
- a Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University , Xuzhou , Jiangsu , China
| | - Dazhi Gao
- a Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University , Xuzhou , Jiangsu , China.,d The Department of Radiology , Nanjing General Hospital, Nanjing Military Command of PLA , Nanjing , Jiangsu , China
| | - Baofu Zhang
- a Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University , Xuzhou , Jiangsu , China
| | - Maojin Zheng
- b Department of Pathology , School of Biomedical Sciences, Xuzhou Medical University , Xuzhou , Jiangsu , China
| | - Mingyin Lun
- a Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University , Xuzhou , Jiangsu , China
| | - Mengxue Wei
- a Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University , Xuzhou , Jiangsu , China
| | - Rui Duan
- a Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University , Xuzhou , Jiangsu , China
| | - Maomao Guo
- a Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University , Xuzhou , Jiangsu , China
| | - Jiajun Hua
- a Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University , Xuzhou , Jiangsu , China
| | - Qian Liu
- a Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University , Xuzhou , Jiangsu , China
| | - Jin Bai
- a Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University , Xuzhou , Jiangsu , China
| | - Hui Liu
- b Department of Pathology , School of Biomedical Sciences, Xuzhou Medical University , Xuzhou , Jiangsu , China.,c The Affiliated Hospital of Xuzhou Medical University , Xuzhou , Jiangsu , China
| | - Junnian Zheng
- a Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University , Xuzhou , Jiangsu , China.,c The Affiliated Hospital of Xuzhou Medical University , Xuzhou , Jiangsu , China
| | - Hong Yao
- a Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University , Xuzhou , Jiangsu , China
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