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Wang MD, Lv SD, Diao YK, Xu JH, Chen FJ, Li YC, Gu WM, Wang H, Yang YZ, Zeng YY, Zhou YH, Wang XM, Li J, Chen TH, Liang YJ, Yao LQ, Gu LH, Wu H, Xu XF, Li C, Shen F, Yang T. Risk stratification model for predicting distant metastasis after hepatectomy for hepatocellular carcinoma: A multi-institutional analysis. Biosci Trends 2025; 19:211-220. [PMID: 40044158 DOI: 10.5582/bst.2024.01387] [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] [Indexed: 05/13/2025]
Abstract
Distant metastasis after hepatectomy for hepatocellular carcinoma (HCC) significantly impairs long-term outcome. This study aimed to identify patterns, risk factors, and develop a prediction model for distant metastasis at first recurrence following HCC resection. This multi-center retrospective study included patients undergoing curative hepatectomy for HCC. Risk factors for distant metastasis were identified using Cox regression. A nomogram was constructed and validated using the concordance index (C-index) and calibration curves. Among 2,705 patients, 1,507 experienced recurrence, with 342 (22.7 per cent) developing distant metastasis. Common metastatic sites included extrahepatic vessels (36.2 per cent), lungs (26.0 per cent), and lymph nodes (20.8 per cent). Patients with distant metastasis had significantly worse 5-year overall survival compared to those with intrahepatic recurrence (9.1 versus 41.1 per cent, p < 0.001). Independent risk factors included preoperative tumor rupture, tumor size over 5.0 cm, multiple tumors, satellite nodules, macro- and microvascular invasion, narrow resection margin, and intraoperative blood transfusion. The nomogram demonstrated excellent discrimination (C-index > 0.85) and accurately stratified patients into three risk categories. In conclusion, distant metastasis at first recurrence following HCC resection was associated with poor prognosis. The proposed nomogram facilitates accurate prediction of distant metastasis, potentially informing personalized postoperative monitoring and interventions for high-risk patients.
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Affiliation(s)
- Ming-Da Wang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
- Eastern Hepatobiliary Clinical Research Institute, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
| | - Shao-Dong Lv
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
| | - Yong-Kang Diao
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
- Eastern Hepatobiliary Clinical Research Institute, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
| | - Jia-Hao Xu
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
- Eastern Hepatobiliary Clinical Research Institute, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
| | - Fu-Jie Chen
- Department of Graduate, Bengbu Medical College, Bengbu, China
| | - Yu-Chen Li
- Department of Graduate, Bengbu Medical College, Bengbu, China
| | - Wei-Min Gu
- The First Department of General Surgery, the Fourth Hospital of Harbin, Heilongjiang, China
| | - Hong Wang
- Department of General Surgery, Liuyang People's Hospital, Hunan, China
| | - Yu-Ze Yang
- Department of Hepatobiliary and Pancreatic Surgery, General Surgery Centre, First Hospital of Jilin University, Changchun, China
| | - Yong-Yi Zeng
- Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital, Fujian Medical University, Fujian, China
| | - Ya-Hao Zhou
- Department of Hepatobiliary Surgery, Pu'er People's Hospital, Yunnan, China
| | - Xian-Ming Wang
- Department of General Surgery, First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong, China
| | - Jie Li
- Department of Hepatobiliary Surgery, Fuyang People's Hospital, Anhui, China
| | - Ting-Hao Chen
- Department of General Surgery, Ziyang First People's Hospital, Sichuan, China
| | - Ying-Jian Liang
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Harbin Medical University, Heilongjiang, China
| | - Lan-Qing Yao
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
- Eastern Hepatobiliary Clinical Research Institute, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
| | - Li-Hui Gu
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
- Eastern Hepatobiliary Clinical Research Institute, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
| | - Han Wu
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
- Eastern Hepatobiliary Clinical Research Institute, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
| | - Xin-Fei Xu
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
- Eastern Hepatobiliary Clinical Research Institute, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
| | - Chao Li
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
- Eastern Hepatobiliary Clinical Research Institute, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
| | - Feng Shen
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
- Eastern Hepatobiliary Clinical Research Institute, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
| | - Tian Yang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
- Eastern Hepatobiliary Clinical Research Institute, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
- Department of Graduate, Bengbu Medical College, Bengbu, China
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Magyar CTJ, Rajendran L, Li Z, Banz V, Vogel A, O'Kane GM, Chan ACY, Sapisochin G. Precision surgery for hepatocellular carcinoma. Lancet Gastroenterol Hepatol 2025; 10:350-368. [PMID: 39993401 DOI: 10.1016/s2468-1253(24)00434-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Revised: 12/12/2024] [Accepted: 12/17/2024] [Indexed: 02/26/2025]
Abstract
Hepatocellular carcinoma arises in the setting of cirrhosis in most cases, requiring multidisciplinary input to define resectability. In this regard, more precise surgical management considers patient factors and anatomical states, including resection margins, tumour biology, and perioperative therapy. Together with advances in surgical techniques, this integrated approach has resulted in considerable improvements in patient morbidity and oncological outcomes. Despite this, recurrence rates in hepatocellular carcinoma remain high. As the systemic treatment landscape in hepatocellular carcinoma continues to evolve and locoregional options are increasingly used, we review current and future opportunities to individualise the surgical management of patients with hepatocellular carcinoma.
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Affiliation(s)
- Christian Tibor Josef Magyar
- HPB Surgical Oncology, University Health Network, Toronto, ON, Canada; Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada; Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Luckshi Rajendran
- HPB Surgical Oncology, University Health Network, Toronto, ON, Canada; Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada; Division of Transplant Surgery, Henry Ford Hospital, Detroit, MI, USA
| | - Zhihao Li
- HPB Surgical Oncology, University Health Network, Toronto, ON, Canada; Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
| | - Vanessa Banz
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Arndt Vogel
- Medical Oncology, Princess Margaret Cancer Center, University Health Network, Toronto, ON, Canada; Division of Gastroenterology and Hepatology, Toronto General Hospital, Toronto, ON, Canada; Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hanover, Germany
| | - Grainne Mary O'Kane
- Medical Oncology, Princess Margaret Cancer Center, University Health Network, Toronto, ON, Canada; Department of Medicine Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada; St Vincent's University Hospital and School of Medicine, University College Dublin, Dublin, Ireland
| | - Albert Chi-Yan Chan
- Department of Surgery, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Gonzalo Sapisochin
- HPB Surgical Oncology, University Health Network, Toronto, ON, Canada; Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada.
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Emmamally M, Sobnach S, Khan R, Kotze U, Bernon M, Sonderup MW, Spearman CW, Jonas E. Prevalence, management and outcomes of pulmonary metastases in hepatocellular carcinoma: a systematic review and meta-analysis. HPB (Oxford) 2024; 26:1339-1348. [PMID: 39168776 DOI: 10.1016/j.hpb.2024.08.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Revised: 06/11/2024] [Accepted: 08/02/2024] [Indexed: 08/23/2024]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) presents a significant global health burden, with varying survival rates across regions. The presence of pulmonary metastases (PM) in HCC predicts a poorer prognosis, yet the global understanding of the progression and management is limited. METHODS This study aims to systematically review the burden of PM in HCC, document current treatment approaches, and evaluate treatment effectiveness through meta-analysis. A comprehensive literature search was conducted across multiple databases. Articles were screened, and data extraction was performed independently by two reviewers. Statistical analyses were conducted to synthesise data and assess treatment outcomes. RESULTS A total of 82 articles were included, comprising a population of 3241 participants with documented PM. Our analysis revealed a linear relationship between the HCC population size and the occurrence of PM (p < 0.005). Surgical intervention demonstrated the lowest hazard ratio (0.128) and significantly improved survival rates compared to other treatment modalities. However, data quality limitations underscore the need for further research to delineate patient subsets benefitting from surgical intervention for PM. CONCLUSION Our findings advocate for continued investigation into PM management strategies, notably the role of surgical resection alongside systemic therapies, to improve outcomes in HCC patients with PM.
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Affiliation(s)
- Muhammad Emmamally
- Surgical Gastroenterology Unit, Division of General Surgery, University of Cape Town Health Sciences Faculty and Groote Schuur Hospital, Cape Town, South Africa
| | - Sanju Sobnach
- Surgical Gastroenterology Unit, Division of General Surgery, University of Cape Town Health Sciences Faculty and Groote Schuur Hospital, Cape Town, South Africa
| | - Rufaida Khan
- Surgical Gastroenterology Unit, Division of General Surgery, University of Cape Town Health Sciences Faculty and Groote Schuur Hospital, Cape Town, South Africa
| | - Urda Kotze
- Surgical Gastroenterology Unit, Division of General Surgery, University of Cape Town Health Sciences Faculty and Groote Schuur Hospital, Cape Town, South Africa
| | - Marc Bernon
- Surgical Gastroenterology Unit, Division of General Surgery, University of Cape Town Health Sciences Faculty and Groote Schuur Hospital, Cape Town, South Africa
| | - Mark W Sonderup
- Division of Hepatology, Department of Medicine, Faculty of Health Sciences, University of Cape Town Faculty and Groote Schuur Hospital, Cape Town, South Africa
| | - C Wendy Spearman
- Division of Hepatology, Department of Medicine, Faculty of Health Sciences, University of Cape Town Faculty and Groote Schuur Hospital, Cape Town, South Africa
| | - Eduard Jonas
- Surgical Gastroenterology Unit, Division of General Surgery, University of Cape Town Health Sciences Faculty and Groote Schuur Hospital, Cape Town, South Africa.
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Paganetti C, Heigl A, Rosenberg R, Vetter M, Haslbauer J, Steuerwald M. Case report: 65-year-old man with metachronous left sided adrenal metastasis of hepatocellular carcinoma. Int J Surg Case Rep 2024; 119:109683. [PMID: 38688153 PMCID: PMC11067464 DOI: 10.1016/j.ijscr.2024.109683] [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: 02/13/2024] [Revised: 04/18/2024] [Accepted: 04/20/2024] [Indexed: 05/02/2024] Open
Abstract
INTRODUCTION AND IMPORTANCE Due to therapeutic advances and improvements in follow-up care, the diagnosis and treatment of extrahepatic metastases of hepatocellular carcinoma [HCC] have gained clinical significance. However, adrenal gland metastases of HCC remain a rare clinical encounter. Several systemic and local treatment options are discussed in current literature. Adrenalectomy in cases of isolated adrenal metastases with well-controlled intrahepatic lesions has been shown to benefit patients in case series. PRESENTATION OF THE CASE This 65-year-old patient presented with suspected metachronous left sided adrenal metastasis seven years after bisegmentectomy for HCC and after undergoing trans-arterial chemoembolization [TACE] for multifocal intrahepatic recurrences while being listed for liver transplantation "beyond Milan criteria". Adrenalectomy was suggested for histopathological confirmation of the suspected metastasis and re-consideration for liver transplant. The resection was performed laparoscopically and metastasis of HCC was confirmed in histopathological analysis. Postoperatively, the patient recovered quickly. However, the patient decided against re-listing for liver transplantation. CLINICAL DISCUSSION Current literature suggests, that minimally-invasive adrenalectomy should be considered in patients with no more than two extrahepatic lesions, a Child-Pugh-Score of less than A5, low alpha-fetoprotein [AFP] levels <100 ng/ml and size <3 cm. The oncological goal should be to achieve a tumor free extrahepatic situation with a potential oncological benefit. CONCLUSION Our patient presented as an ideal candidate for resection of the adrenal gland metastasis and could have been re-assessed postoperatively for liver transplantation. Still, more research is needed to improve patient-selection for metastasectomy in HCC.
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Affiliation(s)
- Ch Paganetti
- Department of Surgery, Cantonal Hospital Baselland, Liestal, Switzerland.
| | - A Heigl
- Department of Surgery, Cantonal Hospital Baselland, Liestal, Switzerland
| | - R Rosenberg
- Department of Surgery, Cantonal Hospital Baselland, Liestal, Switzerland
| | - M Vetter
- Department of Oncology, Cancer Center, Medical University Clinic, Cantonal Hospital Baselland, Liestal, Switzerland
| | - J Haslbauer
- Department of Pathology, Cantonal Hospital Baselland, Liestal, Switzerland
| | - M Steuerwald
- Praxis für Gastroenterologie und Hepatologie, Liestal, Switzerland
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Abdelhamed W, El-Kassas M. Hepatocellular carcinoma recurrence: Predictors and management. LIVER RESEARCH (BEIJING, CHINA) 2023; 7:321-332. [PMID: 39958776 PMCID: PMC11791921 DOI: 10.1016/j.livres.2023.11.004] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/03/2023] [Revised: 09/14/2023] [Accepted: 11/17/2023] [Indexed: 02/18/2025]
Abstract
Hepatocellular carcinoma (HCC), the sixth most common cancer globally, is associated with high mortality rates and more than 830,000 annual deaths. Despite advances in the available management options including surgical resection and local ablative therapies, recurrence rates after the initial treatment exceed 50%, even among patients who have undergone curative-intent therapy. Moreover, postsurgical HCC recurrence occurs in about 70% of cases five years postoperatively. The management of recurrent HCC remains undefined. This review discusses different predictors for HCC recurrence after each treatment modality and different approaches available to stratify these patients. More specific guidelines for managing HCC recurrence and strict surveillance protocols for such recurrence after initial HCC management are needed.
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Affiliation(s)
| | - Mohamed El-Kassas
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt
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Gao YX, Ning QQ, Yang PX, Guan YY, Liu PX, Liu ML, Qiao LX, Guo XH, Yang TW, Chen DX. Recent advances in recurrent hepatocellular carcinoma therapy. World J Hepatol 2023; 15:460-476. [PMID: 37206651 PMCID: PMC10190692 DOI: 10.4254/wjh.v15.i4.460] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Revised: 12/20/2022] [Accepted: 03/24/2023] [Indexed: 04/20/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most prevalent form of primary liver cancer, accounting for 75%-85% of cases. Although treatments are given to cure early-stage HCC, up to 50%-70% of individuals may experience a relapse of the illness in the liver after 5 years. Research on the fundamental treatment modalities for recurrent HCC is moving significantly further. The precise selection of individuals for therapy strategies with established survival advantages is crucial to ensuring better outcomes. These strategies aim to minimize substantial morbidity, support good life quality, and enhance survival for patients with recurrent HCC. For individuals with recurring HCC after curative treatment, no approved therapeutic regimen is currently available. A recent study presented novel approaches, like immunotherapy and antiviral medication, to improve the prognosis of patients with recurring HCC with the apparent lack of data to guide the clinical treatment. The data supporting several neoadjuvant and adjuvant therapies for patients with recurring HCC are outlined in this review. We also discuss the potential for future clinical and translational investigations.
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Affiliation(s)
- Yu-Xue Gao
- Beijing Institute of Hepatology, Beijing You An Hospital, Capital Medical University, Beijing 100069, China
- Beijing Precision Medicine and Transformation Engineering Technology Research Center of Hepatitis and Liver Cancer, Beijing 100069, China
| | - Qi-Qi Ning
- Beijing Institute of Hepatology, Beijing You An Hospital, Capital Medical University, Beijing 100069, China
- Beijing Precision Medicine and Transformation Engineering Technology Research Center of Hepatitis and Liver Cancer, Beijing 100069, China
| | - Peng-Xiang Yang
- Beijing Institute of Hepatology, Beijing You An Hospital, Capital Medical University, Beijing 100069, China
- Beijing Precision Medicine and Transformation Engineering Technology Research Center of Hepatitis and Liver Cancer, Beijing 100069, China
| | - Yuan-Yue Guan
- Beijing Institute of Hepatology, Beijing You An Hospital, Capital Medical University, Beijing 100069, China
- Beijing Precision Medicine and Transformation Engineering Technology Research Center of Hepatitis and Liver Cancer, Beijing 100069, China
| | - Peng-Xiang Liu
- Beijing Institute of Hepatology, Beijing You An Hospital, Capital Medical University, Beijing 100069, China
- Beijing Precision Medicine and Transformation Engineering Technology Research Center of Hepatitis and Liver Cancer, Beijing 100069, China
| | - Meng-Lu Liu
- Beijing Institute of Hepatology, Beijing You An Hospital, Capital Medical University, Beijing 100069, China
- Beijing Precision Medicine and Transformation Engineering Technology Research Center of Hepatitis and Liver Cancer, Beijing 100069, China
| | - Lu-Xin Qiao
- Beijing Institute of Hepatology, Beijing You An Hospital, Capital Medical University, Beijing 100069, China
- Beijing Precision Medicine and Transformation Engineering Technology Research Center of Hepatitis and Liver Cancer, Beijing 100069, China
| | - Xiang-Hua Guo
- Beijing Institute of Hepatology, Beijing You An Hospital, Capital Medical University, Beijing 100069, China
- Beijing Precision Medicine and Transformation Engineering Technology Research Center of Hepatitis and Liver Cancer, Beijing 100069, China
| | - Tong-Wang Yang
- Beijing Institute of Hepatology, Beijing You An Hospital, Capital Medical University, Beijing 100069, China
- Academician Workstation, Changsha Medical University, Changsha 410219, Hunan Province, China
- Hunan Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, Changsha Medical University, Changsha 410219, Hunan Province, China
| | - De-Xi Chen
- Beijing Institute of Hepatology, Beijing You An Hospital, Capital Medical University, Beijing 100069, China
- Beijing Precision Medicine and Transformation Engineering Technology Research Center of Hepatitis and Liver Cancer, Beijing 100069, China
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Papaconstantinou D, Tsilimigras DI, Pawlik TM. Recurrent Hepatocellular Carcinoma: Patterns, Detection, Staging and Treatment. J Hepatocell Carcinoma 2022; 9:947-957. [PMID: 36090786 PMCID: PMC9450909 DOI: 10.2147/jhc.s342266] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Accepted: 08/29/2022] [Indexed: 01/27/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths worldwide with the incidence of recurrence being as high as 88% even among patients who have undergone curative-intent treatment. Despite improvements in overall survival, recurrence remains a challenge necessitating accurate reappraisal of patient and disease status. To that end, accurate staging of recurrent HCC is a necessity to provide better care for these patients. Risk factors for poor survival after HCC recurrence have been identified and include characteristics of the primary disease, such as tumor multifocality, large size (≥5 cm), macroscopic vascular or microscopic lymphovascular invasion, preoperative a-fetoprotein (AFP) levels, R0 resection, and the presence of impaired liver function. Close surveillance with imaging is warranted following curative-intent therapy, with magnetic resonance imaging (MRI) being the preferred approach to identify small, early recurrent HCCs. Treatment decisions at the time of recurrence involve ruling out extrahepatic disease and identifying candidates for potentially curative-intent repeat treatment options. Patients with recurrent disease are, however, very diverse in terms of tumor morphology and biologic behavior, as well as residual hepatic functional reserve. Patients with preserved liver function may benefit from repeat liver resection or ablation. Patients with recurrence within the Milan criteria may even be candidates for salvage liver transplantation, while multimodality treatment with combination of liver-directed therapies appears to enhance oncologic outcomes for individuals with advanced recurrent disease. A “one-size-fits-all” approach in staging recurrent HCC does not exist. Rather, individualized and evidence-based decision-making is necessary in order to optimize outcomes for patients with recurrent HCC.
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Affiliation(s)
- Dimitrios Papaconstantinou
- Third Department of Surgery, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Diamantis I Tsilimigras
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA
| | - Timothy M Pawlik
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA
- Correspondence: Timothy M Pawlik, Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, The Ohio State University, Wexner Medical Center, 395 W. 12th Ave., Suite 670, Columbus, OH, USA, Tel +1 614 293 8701, Fax +1 614 293 4063, Email
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Arita J, Ichida A, Nagata R, Mihara Y, Kawaguchi Y, Ishizawa T, Akamatsu N, Kaneko J, Hasegawa K. Conversion surgery after preoperative therapy for advanced hepatocellular carcinoma in the era of molecular targeted therapy and immune checkpoint inhibitors. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2022; 29:732-740. [PMID: 35306748 DOI: 10.1002/jhbp.1135] [Citation(s) in RCA: 41] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Revised: 01/06/2022] [Accepted: 01/24/2022] [Indexed: 11/12/2022]
Abstract
BACKGROUND Optimal strategies for advanced hepatocellular carcinoma (HCC) tumors, such as those with vascular tumor thrombus and those with extrahepatic metastases are unclear. METHODS A literature review was conducted focusing on conversion surgery for HCC after molecular targeted therapy and therapy using immune checkpoint inhibitors. RESULTS Upfront surgical resection of advanced HCC tumors has been challenged at some institutions because of lack of promising therapeutic options. Preoperative transcatheter arterial chemoembolization, hepatic arterial infusion chemotherapy, and radiotherapy in patients with unresectable HCC were developed to improve long-term outcome, but the results were not promising. Nonetheless, the recent advent of molecular targeted therapies and immune check-point inhibitors, enabling frequent tumor responses, has accelerated the use of conversion surgery after these therapies in patients with initially unresectable HCC. Increasing numbers of conversion surgeries after lenvatinib therapy has been reported, and the first prospective clinical trial assessing conversion surgery after lenvatinib therapy in initially unresectable HCC has been commenced. Furthermore, the superiority of combination therapy using atezolizumab and bevacizumab over sorafenib, a conventional first-line drug for unresectable HCC, in terms of overall survival and tumor response has been demonstrated, and the use of this regimen alongside conversion surgery is expected in addition to lenvatinib. CONCLUSION The literature demonstrated the feasibility of conversion surgery after systemic therapy. Further clinical investigation of surgery after systemic therapy for advanced HCC may be undertaken by clearly distinguishing the tumor status as technically unresectable or oncologically unresectable but technically resectable.
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Affiliation(s)
- Junichi Arita
- Hepato-Biliary and Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
| | - Akihiko Ichida
- Hepato-Biliary and Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
| | - Rihito Nagata
- Hepato-Biliary and Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
| | - Yuichiro Mihara
- Hepato-Biliary and Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
| | - Yoshikuni Kawaguchi
- Hepato-Biliary and Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
| | - Takeaki Ishizawa
- Hepato-Biliary and Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
| | - Nobuhisa Akamatsu
- Hepato-Biliary and Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
| | - Junichi Kaneko
- Hepato-Biliary and Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
| | - Kiyoshi Hasegawa
- Hepato-Biliary and Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
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9
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Shimagaki T, Yoshizumi T, Itoh S, Iseda N, Tomiyama T, Morinaga A, Wang H, Kurihara T, Nagao Y, Toshima T, Harada N, Kinjo N, Maeda T, Mori M. The ratio of serum des-gamma-carboxy prothrombin to tumor volume as a new biomarker for early recurrence of resected hepatocellular carcinoma. Hepatol Res 2022; 52:381-389. [PMID: 35089647 DOI: 10.1111/hepr.13750] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 12/24/2021] [Accepted: 01/17/2022] [Indexed: 02/08/2023]
Abstract
BACKGROUND Early recurrence (ER) of hepatocellular carcinoma (HCC) (within 1 year after resection) is known to be a poor prognostic factor. The aim was to identify the risk factors associated with ER after HCC resection. METHODS Data were analyzed retrospectively from patients who underwent primary resection for HCC from two hospitals. For cross-validation, HCC resection cases were divided into the training and testing cohort. The clinicopathological factors between the ER and non-ER groups and factors for predicting ER and prognosis after HCC resection were compared. RESULTS Out of 173 patients in the training dataset, 33 patients had ER and the ER group showed larger tumor size, more intrahepatic metastasis (IM), and a higher ratio of serum des-gamma-carboxy prothrombin (DCP) to tumor volume (TV) (DCP/TV) than the non-ER group. Out of 203 patients in the testing dataset, 30 patients had ER and the ER group demonstrated larger tumor size, more IM, and higher serum alpha-fetoprotein, AFP/TV, DCP/TV, AFP/tumor maximum diameter (TMD), and DCP/TMD than the non-ER group. The patients were divided into high and low DCP/TV groups and high serum DCP/TV was associated with unfavorable overall survival in the training and testing dataset. Multivariate analysis confirmed that high serum DCP/TV and IM were independently associated with ER. CONCLUSION Preoperative high serum DCP/TV may be useful for stratifying patients at risk of early HCC recurrence after curative resection.
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Affiliation(s)
- Tomonari Shimagaki
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.,Department of Surgery, Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital, Hiroshima, Japan
| | - Tomoharu Yoshizumi
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Shinji Itoh
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Norifumi Iseda
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Takahiro Tomiyama
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Akinari Morinaga
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Huanlin Wang
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Takeshi Kurihara
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yoshihiro Nagao
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Takeo Toshima
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Noboru Harada
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Nao Kinjo
- Department of Surgery, Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital, Hiroshima, Japan
| | - Takashi Maeda
- Department of Surgery, Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital, Hiroshima, Japan
| | - Masaki Mori
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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10
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Moon SY, Han SY, Baek YH. A case report of advanced hepatocellular carcinoma treated with hepatic arterial infusion chemotherapy and sorafenib combination therapy followed by metastasectomy of lung and muscle metastases. JOURNAL OF LIVER CANCER 2022; 22:57-62. [PMID: 37383533 PMCID: PMC10035714 DOI: 10.17998/jlc.2021.12.20] [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: 11/17/2021] [Revised: 12/08/2021] [Accepted: 12/12/2021] [Indexed: 06/30/2023]
Abstract
Currently, various tyrosine kinase inhibitors and immune checkpoint inhibitors have been suggested in the treatment guidelines for advanced hepatocellular carcinoma (HCC). However, sorafenib was the only systemic drug approved 10 years ago. In 2010, a woman diagnosed with HCC rupture and multiple lung metastases visited our hospital. At the time of visiting our hospital, she had undergone transarterial chemoembolization at another hospital to control bleeding due to HCC rupture. We treated her with hepatic arterial infusion chemotherapy and sorafenib combination therapy to increase the control of intrahepatic tumors in consideration of the modest efficacy of sorafenib. The intrahepatic tumor was almost controlled. Metastasectomy was performed to control lung oligometastasis. Subsequently, additional muscle metastasis was confirmed, and metastasectomy was performed. Although this is a very rare case, it shows that a multidisciplinary approach can improve the prognosis of patients with HCC.
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Affiliation(s)
- Sang Yi Moon
- Department of Internal Medicine, Dong-A University College of Medicine, Busan, Korea
| | - Sang Young Han
- Department of Internal Medicine, On Hospital, Busan, Korea
| | - Yang-Hyun Baek
- Department of Internal Medicine, Dong-A University College of Medicine, Busan, Korea
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11
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Long HY, Huang TY, Xie XY, Long JT, Liu BX. Treatment strategies for hepatocellular carcinoma with extrahepatic metastasis. World J Clin Cases 2021; 9:5754-5768. [PMID: 34368295 PMCID: PMC8316954 DOI: 10.12998/wjcc.v9.i21.5754] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2021] [Revised: 04/20/2021] [Accepted: 05/25/2021] [Indexed: 02/06/2023] Open
Abstract
Extrahepatic metastasis (EHM) of hepatocellular carcinoma (HCC) has increasingly been seen due to improved survival with effective management of intrahepatic lesions. The presence of EHM indicates an advanced stage of HCC, for which systemic therapy serves as the standard treatment modality. Since the approval of Sorafenib as the first systemic agent in 2007, it took almost a decade to show its efficacy in both first and further lines of setting until the landscape of systemic drugs was finally expanded. Moreover, with inspiring results from immunotherapy trials in HCC, it appears that the introduction of immunotherapy may lead to an evolution in the portfolio of HCC treatment. Although the locoregional approach in the management of EHM is not recommended for advanced-stage HCC, efforts have been made to demonstrate its efficacy in symptom relief and potential benefit for overall survival. This review provides a summary of recent updates of the systemic agents in the treatment of advanced HCC, with an emphasis on aggressive locoregional management of EHM by various treatment modalities.
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Affiliation(s)
- Hai-Yi Long
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, China
| | - Tong-Yi Huang
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, China
| | - Xiao-Yan Xie
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, China
| | - Jian-Ting Long
- Department of Medical Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
| | - Bao-Xian Liu
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, China
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