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Tabrizian P, Pero A, Schwartz M. Hepatic Resection for Hepatocellular Carcinoma. Clin Liver Dis 2025; 29:59-72. [PMID: 39608958 DOI: 10.1016/j.cld.2024.08.008] [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: 11/30/2024]
Abstract
Hepatic resection has long been considered the preferred treatment for hepatocellular carcinoma (HCC) when feasible, but its role, as well as the outcomes is evolving rapidly. This article explores the impact of the changing demographics of HCC, reviews current criteria for resection, considers the roles of liver transplantation and nonsurgical locoregional therapies vis-a-vis resection, highlights the potential of new systemic therapies (particularly immune checkpoint inhibitors) to improve outcomes, details the common complications associated with resection, and discusses recurrence of HCC after resection and its management.
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Affiliation(s)
- Parissa Tabrizian
- Recanati-Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, 1 Gustave Levy Place, New York, NY 10029, USA
| | - Adriana Pero
- Icahn School of Medicine at Mount Sinai, 1 Gustave Levy Place, New York, NY 10029, USA
| | - Myron Schwartz
- Recanati-Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, 1 Gustave Levy Place, New York, NY 10029, USA.
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Jiang C, Hou GM, Zhang ZH, Qiang ZY, Wang HC, Zhou J, Zeng Y. Anatomic versus nonanatomic resection for intrahepatic cholangiocarcinoma: a systematic review and meta-analysis. Int J Surg 2025; 111:1440-1453. [PMID: 40053809 PMCID: PMC11745696 DOI: 10.1097/js9.0000000000002134] [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: 07/16/2024] [Accepted: 11/05/2024] [Indexed: 03/09/2025]
Abstract
BACKGROUND The value of anatomic resection (AR) in intrahepatic cholangiocarcinoma (ICC) remains controversial. This study compares the perioperative safety and long-term outcomes of AR versus nonanatomic resection (NAR) in ICC patients. METHODS A systematic search was conducted in PubMed, Medline, Embase, Cochrane Library, China National Knowledge Infrastructure(CNKI), and Wanfang database for prospective or retrospective studies comparing the efficacy of AR and NAR in, ICC published to 1 June 2024. Meta-analyses were performed on surgical factors, perioperative outcomes, and long-term prognosis for both the entire cohort and the propensity score-matched (PSM) cohort. The primary outcome measures were overall survival (OS) and disease-free survival (DFS). RESULTS Seven studies, including 1801 ICC patients, were analyzed. In both the entire and the PSM cohort, the AR group demonstrated superior OS (HR=0.71, 95% CI=0.57-0.88, P=0.002 and HR=0.70, 95% CI=0.59-0.83, P<0.0001, respectively) and DFS (HR=0.75, 95% CI=0.62-0.91, P=0.004 and HR=0.68, 95% CI=0.58-0.79, P<0.00001, respectively) compared to the NAR group. AR significantly improves 1-year, 3-year, 5-year DFS, and 5-year OS(all P<0.05). In the PSM cohort, AR and NAR groups showed comparable blood loss, operative times, overall complications, and major complications (all P>0.05). Subgroup analysis revealed that among patients with tumor >5 cm, AR achieved better OS and DFS, whereas patients with tumors ≤5 cm did not experience survival benefits from AR. CONCLUSION This study suggests that AR, compared to NAR, can improve OS and DFS without increasing perioperative risks, particularly in ICC patients with tumors larger than 5 cm.
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Affiliation(s)
- Chuang Jiang
- Department of General Surgery and Laboratory of Liver Surgery, Division of Liver Surgery, State Key Laboratory of Biotherapy and Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Gui-Min Hou
- Department of Hepato-Biliary-Pancreatic Surgery, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Zhi-Hong Zhang
- Department of General Surgery and Laboratory of Liver Surgery, Division of Liver Surgery, State Key Laboratory of Biotherapy and Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Ze-Yuan Qiang
- Department of General Surgery and Laboratory of Liver Surgery, Division of Liver Surgery, State Key Laboratory of Biotherapy and Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Hai-Chuan Wang
- Department of General Surgery and Laboratory of Liver Surgery, Division of Liver Surgery, State Key Laboratory of Biotherapy and Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Jin Zhou
- Department of General Surgery and Laboratory of Liver Surgery, Division of Liver Surgery, State Key Laboratory of Biotherapy and Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Yong Zeng
- Department of General Surgery and Laboratory of Liver Surgery, Division of Liver Surgery, State Key Laboratory of Biotherapy and Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
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Lin ZY, Chen K, Chen JR, Chen WX, Li JF, Li CG, Song GQ, Liu YZ, Wang J, Liu R, Hu MG. Deep Neural Network and Radiomics-based Magnetic Resonance Imaging System for Predicting Microvascular Invasion in Hepatocellular Carcinoma. J Cancer 2024; 15:6223-6231. [PMID: 39513126 PMCID: PMC11540505 DOI: 10.7150/jca.93712] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2023] [Accepted: 09/25/2024] [Indexed: 11/15/2024] Open
Abstract
Background: Accurate preoperative evaluation of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) is crucial for surgeons to make informed decisions regarding appropriate treatment strategies. However, it continues to pose a significant challenge for radiologists. The integration of computer-aided diagnosis utilizing deep learning technology emerges as a promising approach to enhance the prediction accuracy. Methods: This experiment incorporated magnetic resonance imaging (MRI) scans with six different sequences. After a cross-sequence registration preprocess, a deep neural network was employed for the segmentation of hepatocellular carcinoma. The final prediction model was constructed by combining radiomics features with clinical features. The selection of clinical features for the final model was determined through univariate analysis. Results: In this study, we analyzed MRI scans obtained from a cohort of 420 patients diagnosed with HCC. Among them, 140 cases exhibited MVI, while the remaining 280 cases comprised the non-MVI group. The radiomics features demonstrated strong predictive capability for MVI. By extracting radiomic features from each MRI sequence and subsequently integrating them, we achieved the highest area under the curve (AUC) value of 0.794±0.033. Specifically, for tumor sizes ranging from 3 to 5 cm, the AUC reached 0.860±0.065. Conclusions: In this study, we present a fully automatic system for predicting MVI in HCC based on preoperative MRI. Our approach leverages the fusion of radiomics and clinical features to achieve accurate MVI prediction. The system demonstrates robust performance in predicting MVI, particularly in the 3-5 cm tumor group.
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Affiliation(s)
- Zhao-Yi Lin
- Medical School of Chinese PLA, 100853, China
- Faculty of Hepato-Biliary-Pancreatic Surgery, The First Medical Center of Chinese PLA General Hospital, 100853, China
| | - Kuang Chen
- Medical School of Chinese PLA, 100853, China
- Faculty of Hepato-Biliary-Pancreatic Surgery, The First Medical Center of Chinese PLA General Hospital, 100853, China
| | - Jia-Rui Chen
- Medical School of Chinese PLA, 100853, China
- Faculty of Hepato-Biliary-Pancreatic Surgery, The First Medical Center of Chinese PLA General Hospital, 100853, China
| | - Wei-Xiang Chen
- Department of Automation, Tsinghua University, 10084, China
| | - Jin-Feng Li
- Department of Radiology, The First Medical Center of Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China
| | - Cheng-Gang Li
- Faculty of Hepato-Biliary-Pancreatic Surgery, The First Medical Center of Chinese PLA General Hospital, 100853, China
| | - Guo-Quan Song
- Department of Radiology, The First Medical Center of Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China
| | - Yan-Zhe Liu
- Faculty of Hepato-Biliary-Pancreatic Surgery, The First Medical Center of Chinese PLA General Hospital, 100853, China
| | - Jin Wang
- Medical School of Chinese PLA, 100853, China
- Faculty of Hepato-Biliary-Pancreatic Surgery, The First Medical Center of Chinese PLA General Hospital, 100853, China
| | - Rong Liu
- Medical School of Chinese PLA, 100853, China
- Faculty of Hepato-Biliary-Pancreatic Surgery, The First Medical Center of Chinese PLA General Hospital, 100853, China
| | - Ming-Gen Hu
- Medical School of Chinese PLA, 100853, China
- Faculty of Hepato-Biliary-Pancreatic Surgery, The First Medical Center of Chinese PLA General Hospital, 100853, China
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Chen W, Hu Z, Li G, Zhang L, Li T. The State of Systematic Therapies in Clinic for Hepatobiliary Cancers. J Hepatocell Carcinoma 2024; 11:629-649. [PMID: 38559555 PMCID: PMC10981875 DOI: 10.2147/jhc.s454666] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2023] [Accepted: 03/16/2024] [Indexed: 04/04/2024] Open
Abstract
Hepatobiliary cancer (HBC) includes hepatocellular carcinoma and biliary tract carcinoma (cholangiocarcinoma and gallbladder carcinoma), and its morbidity and mortality are significantly correlated with disease stage. Surgery is the cornerstone of curative therapy for early stage of HBC. However, a large proportion of patients with HBC are diagnosed with advanced stage and can only receive systemic treatment. According to the results of clinical trials, the first-line and second-line treatment programs are constantly updated with the improvement of therapeutic effectiveness. In order to improve the therapeutic effect, reduce the occurrence of drug resistance, and reduce the adverse reactions of patients, the treatment of HBC has gradually developed from single-agent therapy to combination. The traditional therapeutic philosophy proposed that patients with advanced HBC are only amenable to systematic therapies. With some encouraging clinical trial results, the treatment concept has been revolutionized, and patients with advanced HBC who receive novel systemic combination therapies with multi-modality treatment (including surgery, transplant, TACE, HAIC, RT) have significantly improved survival time. This review summarizes the treatment options and the latest clinical advances of HBC in each stage and discusses future direction, in order to inform the development of more effective treatments for HBC.
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Affiliation(s)
- Weixun Chen
- Hepatic Surgery Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China
| | - Zhengnan Hu
- Hepatic Surgery Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China
| | - Ganxun Li
- Hepatic Surgery Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China
| | - Lei Zhang
- Hepatic Surgery Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China
| | - Tao Li
- Department of Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, People’s Republic of China
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Zeindler J, Hess GF, von Heesen M, Aegerter N, Reber C, Schmitt AM, Muenst S, Bolli M, Soysal SD, Kollmar O. Anatomic versus non-anatomic liver resection for hepatocellular carcinoma-A European multicentre cohort study in cirrhotic and non-cirrhotic patients. Cancer Med 2024; 13:e6981. [PMID: 38477510 DOI: 10.1002/cam4.6981] [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: 09/04/2023] [Revised: 11/20/2023] [Accepted: 01/18/2024] [Indexed: 03/14/2024] Open
Abstract
BACKGROUND The incidence of hepatocellular carcinoma (HCC) is increasing in the western world over the past decades. As liver resection (LR) represents one of the most efficient treatment options, advantages of anatomic (ALR) versus non-anatomic liver resection (NALR) show a lack of consistent evidence. Therefore, the aim of this study was to investigate complications and survival rates after both resection types. METHODS This is a multicentre cohort study using retrospectively and prospectively collected data. We included all patients undergoing LR for HCC between 2009 and 2020 from three specialised centres in Switzerland and Germany. Complication and survival rates after ALR versus NALR were analysed using uni- and multivariate Cox regression models. RESULTS Two hundred and ninety-eight patients were included. Median follow-up time was 52.76 months. 164/298 patients (55%) underwent ALR. Significantly more patients with cirrhosis received NALR (n = 94/134; p < 0.001). Complications according to the Clavien Dindo classification were significantly more frequent in the NALR group (p < 0.001). Liver failure occurred in 13% after ALR versus 8% after NALR (p < 0.215). Uni- and multivariate cox regression models showed no significant differences between the groups for recurrence free survival (RFS) and overall survival (OS). Furthermore, cirrhosis had no significant impact on OS and RFS. CONCLUSION No significant differences on RFS and OS rates could be observed. Post-operative complications were significantly less frequent in the ALR group while liver specific complications were comparable between both groups. Subgroup analysis showed no significant influence of cirrhosis on the post-operative outcome of these patients.
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Affiliation(s)
- Jasmin Zeindler
- Clarunis, University Centre for Gastrointestinal and Liver Diseases, Basel, Switzerland
| | - Gabriel Fridolin Hess
- Clarunis, University Centre for Gastrointestinal and Liver Diseases, Basel, Switzerland
| | - Maximilian von Heesen
- Department of General, Visceral, Vascular and Pediatric Surgery, University of Saarland, Homburg/Saar, Germany
- Department of General- and Visceral Surgery, University Hospital Göttingen, Göttingen, Germany
| | - Noa Aegerter
- Faculty of Medicine, University of Basel, Basel, Switzerland
| | - Cornelia Reber
- Faculty of Medicine, University of Basel, Basel, Switzerland
| | - Andreas Michael Schmitt
- The Royal Marsden NHS Foundation Trust, London, UK
- Department of Medical Oncology, University Hospital Basel, Basel, Switzerland
| | - Simone Muenst
- Institute of Medical Genetics and Pathology University Hospital Basel, Basel, Switzerland
| | - Martin Bolli
- Clarunis, University Centre for Gastrointestinal and Liver Diseases, Basel, Switzerland
| | - Savas Deniz Soysal
- Clarunis, University Centre for Gastrointestinal and Liver Diseases, Basel, Switzerland
| | - Otto Kollmar
- Clarunis, University Centre for Gastrointestinal and Liver Diseases, Basel, Switzerland
- Department of General, Visceral, Vascular and Pediatric Surgery, University of Saarland, Homburg/Saar, Germany
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Lee B, Cho JY, Han HS, Yoon YS, Lee HW, Lee JS, Kim M, Jo Y. Laparoscopic anatomical versus non-anatomical liver resection for hepatocellular carcinoma in the posterosuperior segments: a propensity score matched analysis. Hepatobiliary Surg Nutr 2023; 12:824-834. [PMID: 38115923 PMCID: PMC10727829 DOI: 10.21037/hbsn-21-578] [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: 12/30/2021] [Accepted: 05/13/2022] [Indexed: 12/21/2023]
Abstract
Background Since laparoscopic anatomical resection (LAR) for tumors, especially located in the posterosuperior (PS) segments of the liver remains difficult, laparoscopic non-anatomical resection (LNAR) are generally preferred. To compare the clinical outcomes between LAR and LNAR for hepatocellular carcinoma (HCC) located in the PS segments. Methods We retrospectively reviewed the data for 1,029 patients who underwent hepatectomy for HCC between 2004 and 2019. Of 167 patients who underwent laparoscopic hepatectomy for HCC in PS segments, 64 underwent LNAR and 103 underwent LAR. Patients were matched one-to-one using propensity score matching (46:46). Results LNAR was associated with significantly shorter operation time (P=0.001), lower estimated blood loss (P=0.001), lower transfusion rate (P=0.006) and shorter hospital stay (P=0.012) than LAR. The respective 1- ,3-, and 5-year overall survival rates (LAR: 95.3%, 87.1%, and 77.8%; LNAR: 96.7%, 91.6%, and 85.0%; P=0.262) and recurrence-free survival rates (LAR: 75.7%, 70.3%, and 68.9%; LNAR: 81.8%, 58.3%, and 55.3%; P=0.879) were similar. The intrahepatic recurrence rate was significantly higher in LNAR group than in LAR group (78.6% vs. 57.1%, P=0.023), but the post-recurrence treatments differed significantly between the two groups (P=0.016); the re-resection rate was much greater in the LNAR group (45.0% vs. 0%) group. The respective 1-, 3-, and 5-year post-recurrence survival rates were similar in the LAR and LNAR groups (P=0.212). After recurrence, survival in re-resection group was significantly greater than not (P=0.026). Conclusions LNAR is safe and feasible for HCC located in PS segments, and provided acceptable oncologic outcomes that are comparable to those of LAR. LNAR can be considered for patient with tumor located in PS segment when LAR is not feasible.
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Affiliation(s)
- Boram Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Jai Young Cho
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Ho-Seong Han
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Yoo-Seok Yoon
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Hae Won Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Jun Suh Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Moonhwan Kim
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Yeongsoo Jo
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
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Abdelhamed W, El-Kassas M. Hepatocellular carcinoma recurrence: Predictors and management. LIVER RESEARCH 2023; 7:321-332. [PMID: 39958776 PMCID: PMC11791921 DOI: 10.1016/j.livres.2023.11.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [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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Wehrle CJ, Woo K, Raj R, Chang J, Stackhouse KA, Dahdaleh F, Augustin T, Joyce D, Simon R, Kim J, Aucejo F, Walsh RM, Kwon DCH, Pawlik TM, Naffouje SA. Comparing Outcomes of Minimally Invasive and Open Hepatectomy for Primary Liver Malignancies in Patients with Low-MELD Cirrhosis. J Gastrointest Surg 2023; 27:2424-2433. [PMID: 37620660 DOI: 10.1007/s11605-023-05817-3] [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: 06/24/2023] [Accepted: 07/31/2023] [Indexed: 08/26/2023]
Abstract
INTRODUCTION Cirrhotic patients with primary liver cancer may undergo curative-intent resection when selected appropriately. Patients with T1 tumors and low-MELD are generally referred for resection. We aim to evaluate whether minimally invasive hepatectomy (MIH) is associated with improved outcomes versus open hepatectomy (OH). METHODS NSQIP hepatectomy database 2014-2021 was used to select patients with T1 Hepatocellular Carcinoma (HCC) or Intra-hepatic Cholangiocarcionoma (IHCC) and low-MELD cirrhosis (MELD ≤ 10) who underwent partial hepatectomy. Propensity score matching was applied between OH and MIH patients, and 30-day postoperative outcomes were compared. Multivariable regression was used to identify predictors of post-hepatectomy liver failure (PHLF) in the selected population. RESULTS There were 922 patients: 494 (53.6%) OH, 372 (40.3%) MIH, and 56 (6.1%) began MIH converted to OH (analyzed with the OH cohort). We matched 354 pairs of patients with an adequate balance between the groups. MIH was associated with lower rates of bile leak (HR 0.37 [0.19-0.72)], PHLF (HR 0.36 [0.15-0.86]), collections requiring drainage (HR 0.30 [0.15-0.63]), postoperative transfusion (HR 0.36 [0.21-0.61]), major (HR 0.45 [0.27-0.77]), and overall morbidity (HR 0.44 [0.31-0.63]), and a two-day shorter median hospitalization (3 vs. 5 days; HR 0.61 [0.45-0.82]). No difference was noted in operative time, wound, respiratory, and septic complications, or mortality. Regression analysis identified ascites, prior portal vein embolization (PVE), additional hepatectomies, Pringle's maneuver, and OH (vs. MIH) as independent predictors of PHLF. CONCLUSION MIH for early-stage HCC/IHCC in low-MELD cirrhotic patients was associated with improved postoperative outcomes over OH. These findings suggest that MIH should be considered an acceptable approach in this population of patients.
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Affiliation(s)
- Chase J Wehrle
- Department of General Surgery, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.
| | - Kimberly Woo
- Department of General Surgery, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, 44195, USA
| | - Roma Raj
- Department of General Surgery, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, 44195, USA
| | - Jenny Chang
- Department of General Surgery, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, 44195, USA
| | - Kathryn A Stackhouse
- Department of General Surgery, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, 44195, USA
| | - Fadi Dahdaleh
- Department of Surgical Oncology, Edward-Elmhurst Health, Elmhurst, IL, USA
| | - Toms Augustin
- Department of General Surgery, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, 44195, USA
| | - Daniel Joyce
- Department of General Surgery, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, 44195, USA
| | - Robert Simon
- Department of General Surgery, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, 44195, USA
| | - Jaekeun Kim
- Department of General Surgery, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, 44195, USA
| | - Federico Aucejo
- Department of General Surgery, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, 44195, USA
| | - R Matthew Walsh
- Department of General Surgery, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, 44195, USA
| | - David C H Kwon
- Department of General Surgery, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, 44195, USA
| | - Timothy M Pawlik
- Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer Research The Ohio State University, Wexner Medical Center, Columbus, OH, USA
| | - Samer A Naffouje
- Department of General Surgery, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, 44195, USA
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Ke Q, Wang L, Lin Z, Liu H, Lou J, Zheng S, Bi X, Wang J, Guo W, Li F, Wang J, Zheng Y, Li J, Cheng S, Zhou W, Liu J, Zeng Y. Anatomic versus non-anatomic resection for early-stage intrahepatic cholangiocarcinoma: a propensity score matching and stabilized inverse probability of treatment weighting analysis. BMC Cancer 2023; 23:850. [PMID: 37697239 PMCID: PMC10496223 DOI: 10.1186/s12885-023-11341-z] [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: 03/23/2023] [Accepted: 08/26/2023] [Indexed: 09/13/2023] Open
Abstract
BACKGROUND Radical resection is still the most cost-effectiveness curative strategy for intrahepatic cholangiocarcinoma (ICC), but it remains controversial on the survival benefit of anatomic resection (AR). In this study, we sought to compare the oncologic outcomes between AR versus non-AR (NAR) as the primary treatment for early-stage ICC patients. METHODS Data of ICC patients who underwent hepatectomy and staged at AJCC I were retrospectively collected from 12 hepatobiliary centers in China between Dec 2012 and Dec 2015. Propensity score matching (PSM) and stabilized inverse probability of treatment weighting (IPTW) analysis were performed to minimize the effect of potential confounders, and the perioperative and long-term outcomes between AR and NAR groups were compared. RESULTS Two hundred seventy-eight ICC patients staged at AJCC I were eligible for this study, including 126 patients receiving AR and 152 patients receiving NAR. Compared to the NAR group, the AR group experienced more intraoperative blood loss before and after PSM or stabilized IPTW (all P > 0.05); AR group also experienced more intraoperative transfusion after stabilized IPTW (P > 0.05). In terms of disease-free survival (DFS) and overall survival (OS), no significant differences were observed between the two groups before and after PSM or stabilized IPTW (all P > 0.05). Multivariable Cox regression analyses found that AR was not an independent prognostic factor for either DFS or OS (all P > 0.05). Further analysis also showed that the survival benefit of AR was not found in any subgroup stratified by Child-Pugh grade (A or B), cirrhosis (presence or absence), tumor diameter (≤ 5 cm or > 5 cm) and pathological type (mass-forming or non-mass-forming) with all P > 0.05. CONCLUSION Surgical approach does not influence the prognosis of patients with stage I primary ICC, and NAR might be acceptable and oncological safety.
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Grants
- 2020QH1242 the Startup Fund for Scientific Research, Fujian Medical University, Fujian, P.R.C
- 2020Y2013 Fujian Provincial Clinical Research Center for Hepatobiliary and Pancreatic Tumors, Fujian, P.R.C
- 201912002 the Key Clinical Specialty Discipline Construction Program of Fuzhou, Fujian, P.R.C
- 62275050 the National Natural Science Foundation of China, P.R.C
- 2019Y9108 the Joint Funds for the Innovation of Science and Technology of Fujian province, Fujian, P.R.C
- 2021ZQNZD013 The Major Scientific Research Project for Middle and Young People funded by the Fujian Provincial Health Commission, Fujian, P.R.C
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Affiliation(s)
- Qiao Ke
- Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, No. 312, Xihong Road, Fuzhou, Fujian, 350025, PR China
- Department of Hepatobiliary Surgery, Clinical Oncology School of Fujian Medical University, No. 420, Fuma Road, Fuzhou, Fujian, 350014, PR China
| | - Lei Wang
- Department of Oncology, the Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Ziguo Lin
- Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, No. 312, Xihong Road, Fuzhou, Fujian, 350025, PR China
| | - Hongzhi Liu
- Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, No. 312, Xihong Road, Fuzhou, Fujian, 350025, PR China
| | - Jianying Lou
- Department of Hepatobiliary Surgery, the Second Hospital Affiliated to Zhejiang University, Hangzhou, China
| | - Shuguo Zheng
- Department of Hepatobiliary Surgery, the Southwest Hospital Affiliated to the Army Medical University, Chongqing, China
| | - Xinyu Bi
- Department of Hepatobiliary Surgery, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Jianming Wang
- Department of Hepatobiliary Surgery, Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science &Technology, Wuhan, China
| | - Wei Guo
- Department of Hepatobiliary Surgery, Beijing Friendship Hospital Affiliated to Capital Medical University, Beijing, China
| | - Fuyu Li
- Department of Hepatobiliary Surgery, the West China Hospital of Sichuan University, Chengdu, China
| | - Jian Wang
- Department of Hepatobiliary Surgery, Renji Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China
| | - Yamin Zheng
- Department of Hepatobiliary Surgery, Xuanwu Hospital Affiliated to Capital Medical University, Beijing, China
| | - Jingdong Li
- Department of Hepatobiliary Surgery, the Affiliated Hospital of Chuanbei Medical University, Nanchong, China
| | - Shi Cheng
- Department of Hepatobiliary Surgery, Tiantan Hospital Affiliated to Capital Medical University, Beijing, China
| | - Weiping Zhou
- Department of Hepatobiliary Surgery III, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China
| | - Jingfeng Liu
- Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, No. 312, Xihong Road, Fuzhou, Fujian, 350025, PR China.
- Department of Hepatobiliary Surgery, Clinical Oncology School of Fujian Medical University, No. 420, Fuma Road, Fuzhou, Fujian, 350014, PR China.
| | - Yongyi Zeng
- Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, No. 312, Xihong Road, Fuzhou, Fujian, 350025, PR China.
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10
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Kim JH, Kim HS, Yoon JH, Joo I, Yoon JH, Kim YJ, Yu SJ, Lee JM. Anatomical ablation for small hepatocellular carcinomas using multiple applicators: a preliminary study. Cancer Imaging 2023; 23:78. [PMID: 37605251 PMCID: PMC10440891 DOI: 10.1186/s40644-023-00597-0] [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: 03/14/2023] [Accepted: 08/02/2023] [Indexed: 08/23/2023] Open
Abstract
BACKGROUND Anatomical ablation, defined as thermal ablation of tumor-bearing small portal territories, may provide excellent local tumor control in peripherally-located small hepatocellular carcinomas (HCC), which has been a major concern with percutaneous ablation alone. PURPOSE To evaluate the technical feasibility and therapeutic outcomes of anatomical ablation using multiple radiofrequency (RF) applicators for the ablation of tumor-bearing small portal territories of peripherally-located small (≤ 4 cm) HCCs. MATERIALS AND METHODS Patients with peripherally-located single HCCs (≤ 4 cm) to be treated with anatomical ablation using multiple RF applicators between January 2020 and March 2022 were enrolled in this prospective study. Anatomical ablation was performed for the index tumor under real-time US-CT/MR fusion imaging guidance, with one or two clustered electrode needles placed across the tumor-bearing portal vein branches. Technical success and complications of anatomical ablations were assessed. Cumulative incidence of local tumor progression (LTP) and recurrence-free survival were estimated using the Kaplan-Meier method. RESULTS Fifty-five HCCs (mean size, 1.77 ± 0.59 cm) in 55 participants (mean age, 66.4 ± 7.7 years; 39 men, 16 women) were treated with anatomical ablation; 98.2% (54/55) technical success was achieved. No major complications were noted. Among the 55 participants, LTP occurred in only one patient who had experienced technical failure of anatomical ablation. Estimated 1- and 2-year cumulative incidences of LTP were 0% and 3.7%, respectively. Five patients developed intrahepatic remote recurrence during the median follow-up period of 19.2 months (range, 3.7-28.8 months); therefore, estimated 1- and 2-year recurrence-free survival was 91.7% and 85.0%, respectively. CONCLUSION Anatomical ablation using multiple RF applicators provided the excellent results of local tumor control in patients with peripherally-located small (≤ 4 cm) HCCs. TRIAL REGISTRATION clinicaltrial.gov identifier: NCT05397860.
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Affiliation(s)
- Jae Hyun Kim
- Department of Radiology, Seoul National University Hospital, 101, Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
| | - Hee Soo Kim
- Department of Radiology, Seoul National University Hospital, 101, Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
| | - Jeong Hee Yoon
- Department of Radiology, Seoul National University Hospital, 101, Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
| | - Ijin Joo
- Department of Radiology, Seoul National University Hospital, 101, Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
| | - Jung-Hwan Yoon
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - Yoon Jun Kim
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - Su Jong Yu
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - Jeong Min Lee
- Department of Radiology, Seoul National University Hospital, 101, Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.
- Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul, Republic of Korea.
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11
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Abstract
Hematomas are often associated with benign processes such as sport-related injuries, postsurgical complications, and medications such as blood thinners. Rarely, hematomas can occur spontaneously without any identifiable cause or recollection of an inciting event. Such events can lead to inaccurately diagnosing a patient, which could delay or alter treatment and worsen the patient's prognosis. This patient reported sudden-onset abdominal pain with radiation to her back and denied any recent medication use or trauma while at home. The case highlights the key radiographic findings of magnetic resonance imaging (MRI) and contrast-enhanced ultrasound to eventually confirm an obscure case of hepatocellular carcinoma and help guide management.
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Affiliation(s)
- Alec Garfinkel
- Radiology, California Northstate University College of Medicine, Elk Grove, USA
| | - Alex Nagourney
- Internal Medicine, California Northstate University College of Medicine, Elk Grove, USA
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12
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Luque LM, Carlevaro CM, Llamoza Torres CJ, Lomba E. Physics-based tissue simulator to model multicellular systems: A study of liver regeneration and hepatocellular carcinoma recurrence. PLoS Comput Biol 2023; 19:e1010920. [PMID: 36877741 PMCID: PMC10019748 DOI: 10.1371/journal.pcbi.1010920] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Revised: 03/16/2023] [Accepted: 02/03/2023] [Indexed: 03/07/2023] Open
Abstract
We present a multiagent-based model that captures the interactions between different types of cells with their microenvironment, and enables the analysis of the emergent global behavior during tissue regeneration and tumor development. Using this model, we are able to reproduce the temporal dynamics of regular healthy cells and cancer cells, as well as the evolution of their three-dimensional spatial distributions. By tuning the system with the characteristics of the individual patients, our model reproduces a variety of spatial patterns of tissue regeneration and tumor growth, resembling those found in clinical imaging or biopsies. In order to calibrate and validate our model we study the process of liver regeneration after surgical hepatectomy in different degrees. In the clinical context, our model is able to predict the recurrence of a hepatocellular carcinoma after a 70% partial hepatectomy. The outcomes of our simulations are in agreement with experimental and clinical observations. By fitting the model parameters to specific patient factors, it might well become a useful platform for hypotheses testing in treatments protocols.
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Affiliation(s)
- Luciana Melina Luque
- Instituto de Física de Líquidos y Sistemas Biológicos - CONICET. La Plata, Argentina
- * E-mail: (LML); (CMC)
| | - Carlos Manuel Carlevaro
- Instituto de Física de Líquidos y Sistemas Biológicos - CONICET. La Plata, Argentina
- Departamento de Ingeniería Mecánica, Universidad Tecnológica Nacional, Facultad Regional La Plata, La Plata, Argentina
- * E-mail: (LML); (CMC)
| | | | - Enrique Lomba
- Instituto de Química Física Rocasolano - CSIC. Madrid, España
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13
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Nevola R, Ruocco R, Criscuolo L, Villani A, Alfano M, Beccia D, Imbriani S, Claar E, Cozzolino D, Sasso FC, Marrone A, Adinolfi LE, Rinaldi L. Predictors of early and late hepatocellular carcinoma recurrence. World J Gastroenterol 2023; 29:1243-1260. [PMID: 36925456 PMCID: PMC10011963 DOI: 10.3748/wjg.v29.i8.1243] [Citation(s) in RCA: 87] [Impact Index Per Article: 43.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Revised: 01/06/2023] [Accepted: 01/30/2023] [Indexed: 02/28/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most frequent liver neoplasm, and its incidence rates are constantly increasing. Despite the availability of potentially curative treatments (liver transplantation, surgical resection, thermal ablation), long-term outcomes are affected by a high recurrence rate (up to 70% of cases 5 years after treatment). HCC recurrence within 2 years of treatment is defined as "early" and is generally caused by the occult intrahepatic spread of the primary neoplasm and related to the tumor burden. A recurrence that occurs after 2 years of treatment is defined as "late" and is related to de novo HCC, independent of the primary neoplasm. Early HCC recurrence has a significantly poorer prognosis and outcome than late recurrence. Different pathogenesis corresponds to different predictors of the risk of early or late recurrence. An adequate knowledge of predictive factors and recurrence risk stratification guides the therapeutic strategy and post-treatment surveillance. Patients at high risk of HCC recurrence should be referred to treatments with the lowest recurrence rate and when standardized to combined or adjuvant therapy regimens. This review aimed to expose the recurrence predictors and examine the differences between predictors of early and late recurrence.
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Affiliation(s)
- Riccardo Nevola
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
- Internal Medicine and Hepatology Unit, Ospedale Evangelico Betania, Naples 80147, Italy
| | - Rachele Ruocco
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
| | - Livio Criscuolo
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
| | - Angela Villani
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
| | - Maria Alfano
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
| | - Domenico Beccia
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
| | - Simona Imbriani
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
| | - Ernesto Claar
- Internal Medicine and Hepatology Unit, Ospedale Evangelico Betania, Naples 80147, Italy
| | - Domenico Cozzolino
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
| | - Ferdinando Carlo Sasso
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
| | - Aldo Marrone
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
| | - Luigi Elio Adinolfi
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
| | - Luca Rinaldi
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
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14
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Yue Q, Zhou Z, Zhang X, Xu X, Liu Y, Wang K, Liu Q, Wang J, Zhao Y, Yin Y. Contrast-enhanced CT findings-based model to predict MVI in patients with hepatocellular carcinoma. BMC Gastroenterol 2022; 22:544. [PMID: 36577952 PMCID: PMC9798548 DOI: 10.1186/s12876-022-02586-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Accepted: 11/16/2022] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Microvascular invasion (MVI) is important in early recurrence and leads to poor overall survival (OS) in hepatocellular carcinoma (HCC). A number of studies have reported independent risk factors for MVI. In this retrospective study, we designed to develop a preoperative model for predicting the presence of MVI in HCC patients to help surgeons in their surgical decision-making and improve patient management. PATIENTS AND METHODS We developed a predictive model based on a nomogram in a training cohort of 225 HCC patients. We analyzed patients' clinical information, laboratory examinations, and imaging features from contrast-enhanced CT. Mann-Whitney U test and multiple logistic regression analysis were used to confirm independent risk factors and develop the predictive model. Internal and external validation was performed on 75 and 77 HCC patients, respectively. Moreover, the diagnostic performance of our model was evaluated using receiver operating characteristic (ROC) curves. RESULTS In the training cohort, maximum tumor diameter (> 50 mm), tumor margin, direct bilirubin (> 2.7 µmol/L), and AFP (> 360.7 ng/mL) were confirmed as independent risk factors for MVI. In the internal and external validation cohort, the developed nomogram model demonstrated good diagnostic ability for MVI with an area under the curve (AUC) of 0.723 and 0.829, respectively. CONCLUSION Based on routine clinical examinations, which may be helpful for clinical decision-making, we have developed a nomogram model that can successfully assess the risk of MVI in HCC patients preoperatively. When predicting HCC patients with a high risk of MVI, the surgeons may perform an anatomical or wide-margin hepatectomy on the patient.
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Affiliation(s)
- Qi Yue
- Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
- Department of Hepatobiliary Surgery, Nanjing Drum Tower Hospital Clinical College of Jiangsu University, Nanjing, China
| | - Zheyu Zhou
- Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
- Department of General Surgery, Nanjing Drum Tower Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Graduate School of Peking Union Medical College, Nanjing, China
| | - Xudong Zhang
- Department of Hepato-Biliary-Pancreatic Surgery, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou, China
| | - Xiaoliang Xu
- Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Yang Liu
- Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Kun Wang
- Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Qiaoyu Liu
- Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Jincheng Wang
- Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Yu Zhao
- Department of Medical Imaging, School of Medical Imaging, Nanjing Medical University, Jiangning, Nanjing, China
| | - Yin Yin
- Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
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15
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Kwon JH, Lee JW, Lee JW, Lee YJ. Effects of Anatomical or Non-Anatomical Resection of Hepatocellular Carcinoma on Survival Outcome. J Clin Med 2022; 11:1369. [PMID: 35268459 PMCID: PMC8910990 DOI: 10.3390/jcm11051369] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Revised: 02/18/2022] [Accepted: 02/28/2022] [Indexed: 02/07/2023] Open
Abstract
Background: The relative benefit of anatomical resection (AR) versus non-anatomical resection (NAR) in hepatocellular carcinoma (HCC) remains controversial. This study compared the survival outcomes and recurrence rates of HCCs analysed according to tumour size and the extent of resection. Methods: Consecutive patients with HCC who underwent curative resection at Asan Medical Center between January 1999 and December 2009 were included in this study. We performed propensity score matching (PSM) according to tumour size to compare the survival outcomes between AR and NAR. A total of 986 patients were analysed; 812 and 174 patients underwent AR and NAR, respectively. Results: Before PSM, regardless of tumour size, the AR group demonstrated significantly better 5-year overall survival (OS) and recurrence-free survival (RFS) than the NAR group (p < 0.001). After PSM, the AR group demonstrated better OS and RFS rates than the NAR group when tumour size was less than 5 cm, but there was no significant difference in the OS and RFS rates between the two groups when tumour size was equal to or greater than 5 cm. In tumours less than 5 cm in size, AR was the most significant factor associated with OS and RFS. However, this prognostic effect of AR was not demonstrated in tumours with sizes equal to or greater than 5 cm. Conclusion: In patients with HCCs smaller than 5 cm, AR reduced the risk of tumour recurrence and improved OS. In HCCs larger than 5 cm, AR and NAR showed comparable survival outcomes.
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Affiliation(s)
- Jae Hyun Kwon
- Department of Surgery, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang-si 14068, Gyeonggi-do, Korea; (J.H.K.); (J.W.L.)
| | - Jung-Woo Lee
- Department of Surgery, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang-si 14068, Gyeonggi-do, Korea; (J.H.K.); (J.W.L.)
| | - Jong Woo Lee
- Department of Surgery, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang-si 14068, Gyeonggi-do, Korea; (J.H.K.); (J.W.L.)
| | - Young Joo Lee
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05535, Korea;
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16
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Fang Y, Yang Y, Li N, Zhang XL, Huang HF. Emerging role of long noncoding RNAs in recurrent hepatocellular carcinoma. World J Clin Cases 2021; 9:9699-9710. [PMID: 34877309 PMCID: PMC8610931 DOI: 10.12998/wjcc.v9.i32.9699] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2021] [Revised: 06/08/2021] [Accepted: 09/08/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) remains one of the most frequent types of liver cancer and is characterized by a high recurrence rate. Recent studies have proposed that long non-coding RNAs (lncRNAs) are potential biomarkers in several recurrent tumor types. It is now well understood that invasion, migration, and metastasis are important factors for tumor recurrence. Moreover, some of the known risk factors for HCC may affect the expression levels of several types of lncRNAs and thus affect the recurrence of liver cancer through lncRNA regulation. In this paper, we review the biological functions, molecular mechanisms, and roles of lncRNAs in HCC and summarize current knowledge about lncRNAs as potential biomarkers in recurrent HCC.
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Affiliation(s)
- Yuan Fang
- Organ Transplantation Center, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan Province, China
| | - Yang Yang
- Department of Otorhinolaryngology, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan Province, China
| | - Na Li
- Organ Transplantation Center, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan Province, China
| | - Xiao-Li Zhang
- Department of Gastrointestinal and Hernia Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan Province, China
| | - Han-Fei Huang
- Organ Transplantation Center, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan Province, China
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17
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He YZ, He K, Huang RQ, Wang ZL, Ye SW, Liu LW, Luo QJ, Hu ZM. Preoperative evaluation and prediction of clinical scores for hepatocellular carcinoma microvascular invasion: a single-center retrospective analysis. Ann Hepatol 2021; 19:654-661. [PMID: 32768591 DOI: 10.1016/j.aohep.2020.07.002] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Revised: 07/07/2020] [Accepted: 07/08/2020] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Microvascular invasion (MVI) of is generally considered to be an important prognostic factor for hepatocellular carcinoma (HCC) after operation, An accurate prediction of MVI before operation is helpful for clinical decision-making before operation. MATERIAL AND METHODS A retrospective analysis of 227 cases of hepatocellular carcinoma patients after hepatectomy has been confirmed the pathological result whether there was MVI, and has been determined the independent risk factors of MVI. Based on these independent risk factors, we constructed a clinical scoring risk model for predicting MVI. RESULTS Among the 227 patients with HCC, 74 (34.6%) were MVI positive. Using receiver operating characteristic (ROC) curve and logistic regression model, we found that alpha-fetoprotein(AFP)≥158 ng/mL(odds ratio[OR] = 4.152,95% confidence interval [95%CI]:1.602∼10.760,p = 0.003), Des-γ-carboxy prothrombin (DCP)≥178mAU/mL(OR = 9.730,95%CI:3.392∼27.910,p < 0.001), circulating tumor cells (CTCs)≥3/3.2 ml(OR = 7.747,95%CI:3.019∼19.881,P < 0.001), maximum tumor diameter≥59 mm(OR = 3.467,95%CI:1.368∼8.669,p = 0.008) and tumor margin unsmoothness(OR = 0.235,95%CI:0.096∼0.573,p = 0.001) were independent risk factors for MVI, they predicted that the area under the curve of MVI was 0.752, 0.777, 0.857, 0.743 and 0.333, respectively. Based on these five independent risk factors, we constructed a clinical scoring risk model for predicting MVI. The model predicts that the area under the curve of MVI is 0.922, and its prevalence rate from 0 to 5 are 3.1%(1/32), 5.3%(4/76), 12.2%(5/41), 66.7%(20/30), 87.9%(29/33), 100%(15/15), respectively (P < 0.001). CONCLUSION Based on AFP, DCP, CTC, maximum tumor diameter and tumor margin unsmoothness, we constructed a model to predict the risk of MVI clinical score, so as to make a more accurate individualized treatment plan before operation, which has important clinical significance and application prospect to improve the curative effect of HCC.
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Affiliation(s)
- Yong Zhu He
- Department of Hepatobiliary Surgery, Zhongshan Hospital Affiliated to Sun Yat-sen University, Zhongshan City, Guangdong Province, China; Guangdong Medical University,Zhanjiang City, Guangdong Province, China
| | - Kun He
- Department of Hepatobiliary Surgery, Zhongshan Hospital Affiliated to Sun Yat-sen University, Zhongshan City, Guangdong Province, China
| | - Rui Qin Huang
- Department of Hepatobiliary Surgery, Zhongshan Hospital Affiliated to Sun Yat-sen University, Zhongshan City, Guangdong Province, China
| | - Ze Liang Wang
- Department of Hepatobiliary Surgery, Zhongshan Hospital Affiliated to Sun Yat-sen University, Zhongshan City, Guangdong Province, China; Guangdong Medical University,Zhanjiang City, Guangdong Province, China
| | - Shao Wei Ye
- Department of Hepatobiliary Surgery, Zhongshan Hospital Affiliated to Sun Yat-sen University, Zhongshan City, Guangdong Province, China; Guangdong Medical University,Zhanjiang City, Guangdong Province, China
| | - Li Wen Liu
- Department of Hepatobiliary Surgery, Zhongshan Hospital Affiliated to Sun Yat-sen University, Zhongshan City, Guangdong Province, China
| | - Qi Jie Luo
- Department of Hepatobiliary Surgery, Zhongshan Hospital Affiliated to Sun Yat-sen University, Zhongshan City, Guangdong Province, China
| | - Ze Min Hu
- Department of Hepatobiliary Surgery, Zhongshan Hospital Affiliated to Sun Yat-sen University, Zhongshan City, Guangdong Province, China.
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18
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Liang X, Zheng J, Xu J, Tao L, Cai J, Liang Y, Feng X, Cai X. Laparoscopic anatomical portal territory hepatectomy using Glissonean pedicle approach (Takasaki approach) with indocyanine green fluorescence negative staining: how I do it. HPB (Oxford) 2021; 23:1392-1399. [PMID: 33593657 DOI: 10.1016/j.hpb.2021.01.014] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2020] [Revised: 11/10/2020] [Accepted: 01/25/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Laparoscopic anatomical resection (LAR) is a highly challenging procedure. This study aimed to describe our experience of the LAR with an indocyanine green fluorescence negative staining (ICGNS) by the Glissonean pedicle transection (Takasaki) approach. METHODS From April 2017 to December 2019, 43 consecutive patients underwent LAR with ICGNS strategy in our medical team. The details of the ICGNS strategy were described. The demographic and clinicopathological data of the included patients were retrospectively analyzed. RESULTS The extent of resections included right hemihepatectomy (n = 12), left hemihepatectom (n = 4), left lateral sectionectomy (n = 3), Right anterior sectionectomy (n = 3), Right posterior sectionectomy (n = 6), central hepatectomy (n = 2), single anterolateral segmentectomy (n = 5), single posterosuperior segmentectomy (n = 6), and bisegmentectomy (n = 2). The mean operation time was 212 ± 53 min, and the median estimated blood loss was 200 (100-300) ml. The overall complication rate was 30.2% (grade I, 14%; grade II, 14%; grade III, 2.3%). The median duration of postoperative hospital stay was 6 (4-7) days. CONCLUSION ICGNS is a safe and feasible LAR strategy that greatly facilitates selecting the liver transection plane, although its benefits need to be verified by large-sample comparative studies.
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Affiliation(s)
- Xiao Liang
- Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China; Key Laboratory of Laparoscopic Technology of Zhejiang Province, China
| | - Junhao Zheng
- Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China
| | - Junjie Xu
- Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China
| | - Liye Tao
- Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China
| | - Jingwei Cai
- Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China
| | - Yuelong Liang
- Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China
| | - Xu Feng
- Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China
| | - Xiujun Cai
- Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China; Key Laboratory of Laparoscopic Technology of Zhejiang Province, China; Zhejiang Minimal Invasive Diagnosis and Treatment Technology Research Center of Severe Hepatobiliary Disease, China; Zhejiang Research and Development Engineering Laboratory of Minimally Invasive Technology and Equipment, China; Zhejiang University Cancer Center, China.
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19
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A novel online calculator based on noninvasive markers (ALBI and APRI) for predicting post-hepatectomy liver failure in patients with hepatocellular carcinoma. Clin Res Hepatol Gastroenterol 2021; 45:101534. [PMID: 33067168 DOI: 10.1016/j.clinre.2020.09.001] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2020] [Revised: 08/12/2020] [Accepted: 09/01/2020] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND AIM Post-hepatectomy liver failure (PHLF) remains the primary cause of in-hospital mortality after hepatectomy. Identifying predictors of PHLF is important to improve surgical safety. We sought to identify the predictive accuracy of two noninvasive markers, albumin-bilirubin (ALBI) and aspartate aminotransferase to platelet count ratio index (APRI), to predict PHLF among patients with hepatocellular carcinoma (HCC), and to build up an online prediction calculator. METHODS Patients who underwent resection for HCC between 2013 and 2016 at 6 Chinese hospitals were retrospectively analyzed. The independent predictors of PHLF were identified using univariate and multivariate analyses; derivative data were used to construct preoperative and postoperative nomogram models. Receiver operating characteristic (ROC) curves for the two predictive models, and ALBI, APRI, Child-Pugh, model for end-stage liver disease (MELD) scores were compared relative to predictive accuracy for PHLF. RESULTS Among the 767 patients in the analytic cohort, 102 (13.3%) experienced PHLF. Multivariable logistic regression analysis identified high ALBI grade (>-2.6) and high APRI grade (>1.5) as independent risk factors associated with PHLF in both the preoperative and postoperative models. Two nomogram predictive models and corresponding web-based calculators were subsequently constructed. The areas under the ROC curves for the postoperative and preoperative models, APRI, ALBI, MELD and Child-Pugh scores in predicting PHLF were 0.844, 0.789, 0.626, 0.609, 0.569, and 0.560, respectively. CONCLUSIONS ALBI and APRI demonstrated more accurate ability to predict PHLF than Child-Pugh and MELD. Two online calculators that combined ALBI and APRI were proposed as useful preoperative and postoperative tools for individually predicting the occurrence of PHLF among patients with HCC.
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Abdelmeguid NE, Khalil MI, Badr NS, Alkhuriji AF, El-Gerbed MS, Sultan AS. Ameliorative effects of colostrum against DMBA hepatotoxicity in rats. Saudi J Biol Sci 2021; 28:2254-2266. [PMID: 33911940 PMCID: PMC8071819 DOI: 10.1016/j.sjbs.2021.01.016] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Revised: 12/09/2020] [Accepted: 01/07/2021] [Indexed: 02/07/2023] Open
Abstract
Colostrum, the sole diet for newborns, is an emerging nutraceutical. To date, the chemopreventive effect of Bovine Colostrum against liver injury induced by the potent carcinogen, 7,12-dimethyl-Benz[a]anthracene (DMBA) is unexplored. Humans are daily exposed to DMBA which is a highly lipophilic environmental organic pollutant. The study aimed to investigate the hepatoprotective role of Bovine Colostrum against DMBA-induced hepatotoxicity using a rat model. Fifty male rats were divided into five groups; GI (control), GII (olive oil, vehicle for DMBA), GIII (DMBA), GIV (DMBA + Bovine Colostrum), GV (Bovine Colostrum). After 12 weeks, body weight changes and mortality were calculated. Histological and ultrastructural examinations of liver tissue were performed. Expressions of p53, TGFβ2, TNF-α, S6K2, and c20orf20 were assessed by RT-PCR. Post-treatment with Bovine Colostrum increased both the body weight and the survival rate of rats treated with DMBA. In addition, remarkable protection against the pathological effect of DMBA was noted. Ultrastructurally, Bovine Colostrum ameliorated/prevented most of the toxic effects of DMBA on hepatocytes, including irregularities of nuclear envelope, clumping, and margination of heterochromatin aggregates, segregated nucleoli, and mitochondrial pleomorphism. Bovine Colostrum administration down-regulated p53, C20orf20, and S6K2 mRNA levels, and up-regulated TNF-α and TGFβ2. In conclusion, Bovine Colostrum have a protective effect against DMBA-induced toxicity on the liver of albino rats. Consequently, Bovine Colostrum may prevent polycyclic aromatic hydrocarbons-induced hepatotoxicity and may be useful in promoting human health if supplemented in the diet.
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Key Words
- BC, Bovine Colostrum
- CAM, Complementary and Alternative Medicine
- Colostrum
- DMBA
- DMBA, 7,12-dimethyl-Benz[a]anthracene
- Hepatoprotective
- IGF, insulin-like growth factor
- IL-1β, cytokines including interleukin-1 beta
- IL-6, interleukin-6
- INF-γ, interferon-gamma
- Nutraceutical
- PAHs, polycyclic aromatic hydrocarbons
- ROS, reactive oxygen species
- S6K, 40S ribosomal protein S6 kinase
- S6K2
- TGFβ, transforming growth factor-beta
- TNFα, tumor necrosis factor-alpha
- p53
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Affiliation(s)
| | - Mahmoud I. Khalil
- Department of Biological Sciences, Faculty of Science, Beirut Arab University, Lebanon
- Molecular Biology Unit, Zoology Department, Faculty of Science, Alexandria University, Alexandria, Egypt
| | - Nada S. Badr
- Zoology Department, Faculty of Science, Damanhur University, Damanhur, Egypt
| | - Afrah F. Alkhuriji
- Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia
| | | | - Ahmed S. Sultan
- Biochemistry Department, Faculty of Science, Alexandria University, Alexandria, Egypt
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21
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Laparoscopic hepatectomy for hepatic angiomyolipoma with preoperative diagnosis of other malignancy: a report of 2 cases. Surg Case Rep 2021; 7:44. [PMID: 33555457 PMCID: PMC7870739 DOI: 10.1186/s40792-021-01125-7] [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: 10/06/2020] [Accepted: 01/27/2021] [Indexed: 11/10/2022] Open
Abstract
Background Hepatic angiomyolipoma (HAML) is a rare liver tumor, and hepatectomy is the only effective treatment. Due to the difficulty of correct diagnosis of HAML before surgery by image studies, more than 36.6% of reported HAMLs are misdiagnosed as other malignant liver tumors before surgery. As there are only few reported cases in which HAMLs were removed using laparoscopic hepatectomy, the effectiveness of laparoscopic hepatectomy for such HAMLs in which are diagnosed as other malignant liver tumor before surgery has not been reported. Case presentation Case 1: a 58-year-old female with a history of treatment for autoimmune hepatitis was preoperatively diagnosed with hepatocellular carcinoma (size: 20 mm) in segment 7 (S7) of the liver. The tumor was removed by laparoscopic partial resection and was diagnosed as a HAML through a pathological examination. The patient’s postoperative course was good, and she was recurrence-free at 37 months after the hepatectomy. Case 2: a 29-year-old female with a history of surgery for a right mature cystic teratoma was referred to our department to receive treatment for a growing 20-mm liver tumor with some calcification, which arose in S3 of the liver. A metastatic liver tumor derived from the mature cystic teratoma was suspected, and laparoscopic left lateral sectionectomy was performed. The liver tumor was diagnosed as a HAML after a pathological examination. The patient’s postoperative course was unremarkable, and more than 54 months have passed since the hepatectomy without any recurrence. Conclusions Two cases in which HAMLs were preoperatively diagnosed as other malignant liver tumor were successfully removed by laparoscopic hepatectomy with a correct postoperative diagnosis. Laparoscopic hepatectomy for the present 2 cases of HAML seemed to be effective for providing a correct diagnosis after the curative removement of liver tumor with a smaller invasion compared to open hepatectomy, and for denying risk of dissemination of the malignant tumor by needle biopsy that had to be considered before ruling out malignant tumor.
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Lin YJ, Ho CM. Is the Rationale of Anatomical Liver Resection for Hepatocellular Carcinoma Universally Adoptable? A Hypothesis-Driven Review. MEDICINA (KAUNAS, LITHUANIA) 2021; 57:131. [PMID: 33540784 PMCID: PMC7913024 DOI: 10.3390/medicina57020131] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/04/2021] [Revised: 01/30/2021] [Accepted: 02/01/2021] [Indexed: 02/08/2023]
Abstract
Surgical resection is the first-line curative treatment modality for resectable hepatocellular carcinoma (HCC). Anatomical resection (AR), described as systematic removal of a liver segment confined by tumor-bearing portal tributaries, may improve survival by reducing the risk of tumor recurrence compared with non-AR. In this article, we propose the rationale for AR and its universal adoption by providing supporting evidence from the advanced understanding of a tumor microenvironment and accumulating clinical experiences of locoregional tumor ablation therapeutics. AR may be advantageous because it completely removes the en-bloc by interrupting tumor vascular supply and thus extirpates the spreading of tumor microthrombi, if they ever exist, within the supplying portal vein. However, HCC is a hypervascular tumor that can promote neoangiogenesis in the local tumor microenvironment, which in itself can break through the anatomical boundary within the liver and even retrieve nourishment from extrahepatic vessels, such as inferior phrenic or omental arteries. Additionally, increasing clinical evidence for locoregional tumor ablation therapies, such as radiofrequency ablation, predominantly performed as a non-anatomical approach, suggests comparable outcomes for surgical resection, particularly in small HCC and colorectal, hepatic metastases. Moreover, liver transplantation for HCC, which can be considered as AR of the whole liver followed by implantation of a new graft, is not universally free from post-transplant tumor recurrence. Overall, AR should not be considered the gold standard among all surgical resection methods. Surgical resection is fundamentally reliant on choosing the optimal margin width to achieve en-bloc tumor niche removal while balancing between oncological radicality and the preservation of postoperative liver function. The importance of this is to liberate surgical resilience in hepatocellular carcinoma. The overall success of HCC treatment is determined by the clearance of the theoretical niche. Developing biomolecular-guided navigation device/technologies may provide surgical guidance toward the total removal of microscopic tumor niche to achieve superior oncological outcomes.
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Affiliation(s)
| | - Cheng-Maw Ho
- Department of Surgery, National Taiwan University Hospital and College of Medicine, 7 Chung-Shan South Road, Taipei 100, Taiwan;
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23
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Is It Just a Matter of Surgical Extension to Achieve the Cure of Hepatocarcinoma? A Meta-Analysis of Propensity-Matched and Randomized Studies for Anatomic Versus Parenchyma-Sparing Liver Resection. J Gastrointest Surg 2021; 25:94-103. [PMID: 31898106 DOI: 10.1007/s11605-019-04494-5] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2019] [Accepted: 11/26/2019] [Indexed: 02/08/2023]
Abstract
BACKGROUND The benefit of anatomic (AR) versus parenchyma-sparing resection (PSR) in hepatocarcinoma (HCC) is still debated. The aim of the study was to compare AR vs. PSR in terms of overall survival (OS) and disease-free survival (DFS). METHODS A systematic review was conducted using Medline and Google Scholar. To reduce intra- and inter-study heterogeneity, only propensity-matched studies and randomized clinical trials (RCT) were evaluated and a generic inverse variance meta-analysis was run. A sub-analysis was performed in case of tumor microvascular invasion (MVI). RESULTS Eleven propensity-matched and one RCT were evaluated, with a total of 3445 patients (AR = 1776 and PSR = 1669). Tumor burden and liver function were comparable among studies (I2 < 50%, p > 0.5). OS was similar between AR and PSR (HR 0.93; 95%CI, 0.75-1.15; p = 0.50, I2 = 41%). DFS was improved in AR at 1 year (RR 0.84; 95%CI, 0.72-0.97; p = 0.02; I2 = 36%) and 3 years (RR 0.90; 95%CI, 0.83-0.98; p = 0.02; I2 = 40%) but not at 5 years (RR 0.94; 95%CI, 0.87-1.01; p = 0.07; I2 = 41%). Furthermore, in the presence of MVI, no difference in OS and DFS was observed between AR and PSR. CONCLUSION When liver function and tumor burden are comparable, AR and PSR achieved similar overall survival. AR improved local control in the early period after surgery. Furthermore, in the presence of MVI, the extension of surgery was not associated with better OS and DFS.
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Chen Z, Zheng Z, Feng L, Huo Z, Huang L, Fu M, Chen Q, Ke Y, Yang J, Hou B. Overexpression of miR-382 Sensitizes Hepatocellular Carcinoma Cells to γδ T Cells by Inhibiting the Expression of c-FLIP. MOLECULAR THERAPY-ONCOLYTICS 2020; 18:467-475. [PMID: 32953981 PMCID: PMC7479278 DOI: 10.1016/j.omto.2020.07.012] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Accepted: 07/27/2020] [Indexed: 12/15/2022]
Abstract
Human γδ T lymphocytes were reported to display anti-tumor effects against multiple cancers, including hepatocellular carcinoma (HCC). Aberrant expression of microRNAs (miRNAs) leads to a low response to immunotherapy. Thirty-five HCC tumor tissues and their adjacent healthy tissues were collected from patients with primary HCC who underwent tumor resection in the Third People’s Hospital of Hainan Province, China. The purity of the resulting γδ T cells was identified by anti-γδ-T cell receptor-phycoerythrin (anti-γδ-TCR-PE) and anti-CD3-fluorescein isothiocyanate (anti-CD3-FITC) antibodies on flow cytometry. Human HCC cell lines HepG2 and PLC were cultured. We observed that ex vivo, expanded human γδ T cells were able to induce cell lysis of HCC. Furthermore, as miR-382 was observed to be downregulated in HCC tissues and cell lines, we found that overexpression of miR-382 increased the sensitivity of HCC cells to γδ T cells. We proved that mRNA of cellular FADD-like interleukin-1β-converting enzyme-inhibitory protein (c-FLIP) was the target of miR-382. Inhibition of c-FLIP by miR-382 significantly promotes the cell lysis of HCC through strengthening the activation caspase 8 induced by γδ T cell treatment. In conclusion, overexpression of miR-382 promotes HCC cell lysis induced by γδ T cells through inhibiting the expression of c-FLIP.
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Affiliation(s)
- Zhong Chen
- Department of General Surgery, The Third People's Hospital of Hainan Province, Sanya City, 572000 Hainan Province, China
| | - Zhiang Zheng
- Department of General Surgery, The Third People's Hospital of Hainan Province, Sanya City, 572000 Hainan Province, China
| | - Lan Feng
- Department of General Surgery, The Third People's Hospital of Hainan Province, Sanya City, 572000 Hainan Province, China
| | - Zhenqing Huo
- Department of General Surgery, The Third People's Hospital of Hainan Province, Sanya City, 572000 Hainan Province, China
| | - Liju Huang
- Department of General Surgery, The Third People's Hospital of Hainan Province, Sanya City, 572000 Hainan Province, China
| | - Mingchang Fu
- Department of General Surgery, The Third People's Hospital of Hainan Province, Sanya City, 572000 Hainan Province, China
| | - Qiuzan Chen
- Department of General Surgery, The Third People's Hospital of Hainan Province, Sanya City, 572000 Hainan Province, China
| | - YanZhuang Ke
- Department of General Surgery, The Third People's Hospital of Hainan Province, Sanya City, 572000 Hainan Province, China
| | - Jinjun Yang
- Department of General Surgery, The Third People's Hospital of Hainan Province, Sanya City, 572000 Hainan Province, China
| | - Benxin Hou
- Department of General Surgery, The Third People's Hospital of Hainan Province, Sanya City, 572000 Hainan Province, China
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Lyu Z, Ma M, Xu Y, Wang X, Zhu Y, Ren W, Li T. Expression and prognostic significance of epithelial tissue-specific transcription factor ESE3 in hepatocellular carcinoma. Int J Clin Oncol 2020; 25:1334-1345. [PMID: 32347431 DOI: 10.1007/s10147-020-01675-0] [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] [Received: 08/09/2019] [Accepted: 03/31/2020] [Indexed: 01/29/2023]
Abstract
BACKGROUND Epithelium-specific ETS 3 (ESE3) is down-regulated frequently in several malignancies and involved in carcinogenesis and progression. However, ESE3 expression pattern and its relationship with clinical features and prognosis in hepatocellular carcinoma (HCC) are still largely unknown. METHODS ESE3 expression was analyzed by quantitative real-time PCR and western blotting in HCC cell lines, and then, it was analyzed by immunohistochemistry in HCC tissues and peritumoral normal tissues from total 94 HCC patients. The relationship between ESE3 expression and clinical features was investigated to illustrate the potential prognostic value in HCC. ESE3 roles on HCC progression were evaluated in vitro and vivo by MTT assay and mice tumor model, respectively. RESULTS ESE3, mainly located in the cytoplasm, was remarkably down-regulated in HCC tissues and cell lines. Low ESE3 expression was positively associated with tumor progression and metastasis features. Kaplan-Meier analysis demonstrated that low ESE3 expression contributed to poor recurrence-free survival (RFS) and overall survival (OS) (both p < 0.01) of patients, and maintained its prognostic value in predicting poor RFS and OS of "Early-stage" HCC patients regardless of clinical features being studied. Multivariate survival analysis was also identified ESE3 as an independent prognostic factor for RFS (p = 0.05 for marginal significance) and OS (p = 0.031). ESE3 expression restoration in cells led to a significant inhibition in HepG2 cell proliferation in vitro and vivo (both p < 0.001). CONCLUSIONS Down-regulated ESE3 expression in HCC tissues could serve as a potential therapeutic target against HCC and appears to be as a poor prognostic indicator for prognosis, especially in "Early-stage" HCC patients.
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Affiliation(s)
- Zhuozhen Lyu
- Department of Infectious Diseases, Shandong Provincial Hospital Affiliated To Shandong University, 324#, Jing 5 Road, Jinan, 250021, China
| | - Mingze Ma
- Department of Infectious Diseases, Shandong Provincial Hospital Affiliated To Shandong University, 324#, Jing 5 Road, Jinan, 250021, China
| | - Yantian Xu
- Department of Liver Transplantation and Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated To Shandong University, 324#, Jing 5 Road, Jinan, 250021, China
| | - Xinxing Wang
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated To Shandong University, 324#, Jing 5 Road, Jinan, 250021, China
| | - Yuhua Zhu
- Department of Infectious Diseases, Shandong Provincial Hospital Affiliated To Shandong University, 324#, Jing 5 Road, Jinan, 250021, China
| | - WanHua Ren
- Department of Infectious Diseases, Shandong Provincial Hospital Affiliated To Shandong University, 324#, Jing 5 Road, Jinan, 250021, China.
| | - Tao Li
- Department of Infectious Diseases, Shandong Provincial Hospital Affiliated To Shandong University, 324#, Jing 5 Road, Jinan, 250021, China.
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Dai Q, Zhang C, Yuan Z, Sun Q, Jiang Y. Current discovery strategies for hepatocellular carcinoma therapeutics. Expert Opin Drug Discov 2020; 15:243-258. [PMID: 31809618 DOI: 10.1080/17460441.2020.1696769] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2019] [Accepted: 11/20/2019] [Indexed: 02/06/2023]
Abstract
Introduction: The global incidence of hepatocellular carcinoma (HCC) is not expected to decline significantly over the next 30 years. And although the latest gene sequencing studies have established its genetic map, the potentially targetable drivers of HCC are, so far, difficult to identify. To date, only seven drugs have been approved by the FDA for unresectable HCC treatment; thus, effective therapeutic breakthroughs are still needed urgently.Areas covered: In this review, the authors discuss both genetic and epigenetic alterations in HCC and introduce the current progress with some of the representative molecular targeting inhibitors, listing some of the approved drugs for the targets of HCC. The structure-activity relationship of molecules (e.g. thalidomide, bortezomil) used for HCC is also discussed.Expert opinion: Effective therapeutic targets and effective drugs for HCC treatment are an urgent unmet need. Better understanding and characterization of genetic and epigenetic alterations, which are important to hepatocarcinogenesis, may help to understand the molecular pathogenesis of HCC, as well as provide novel therapeutic lead compounds for HCC treatment.
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Affiliation(s)
- Qiuzi Dai
- Department of Chemistry, Tsinghua University, Beijing, PR China
- National & Local United Engineering Lab for Personalized Anti-tumor Drugs, The State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Biology, the Graduate School at Shenzhen, Tsinghua University, Shenzhen, PR China
- Shenzhen Bay Laboratory, Shenzhen, PR China
| | - Cunlong Zhang
- Shenzhen Bay Laboratory, Shenzhen, PR China
- National & Local United Engineering Lab for Personalized Anti-tumor Drugs, Shenzhen Kivita Innovative Drug Discovery Institute, The Graduate School at Shenzhen, Tsinghua University, Shenzhen, PR China
| | - Zigao Yuan
- National & Local United Engineering Lab for Personalized Anti-tumor Drugs, The State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Biology, the Graduate School at Shenzhen, Tsinghua University, Shenzhen, PR China
- Shenzhen Bay Laboratory, Shenzhen, PR China
- National & Local United Engineering Lab for Personalized Anti-tumor Drugs, Shenzhen Kivita Innovative Drug Discovery Institute, The Graduate School at Shenzhen, Tsinghua University, Shenzhen, PR China
| | - Qinsheng Sun
- National & Local United Engineering Lab for Personalized Anti-tumor Drugs, The State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Biology, the Graduate School at Shenzhen, Tsinghua University, Shenzhen, PR China
- Shenzhen Bay Laboratory, Shenzhen, PR China
- National & Local United Engineering Lab for Personalized Anti-tumor Drugs, Shenzhen Kivita Innovative Drug Discovery Institute, The Graduate School at Shenzhen, Tsinghua University, Shenzhen, PR China
| | - Yuyang Jiang
- National & Local United Engineering Lab for Personalized Anti-tumor Drugs, The State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Biology, the Graduate School at Shenzhen, Tsinghua University, Shenzhen, PR China
- Shenzhen Bay Laboratory, Shenzhen, PR China
- Department of Pharmacology and Pharmaceutical Sciences, School of Medicine, Tsinghua University, Beijing, P. R. China
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Ju M, Yopp AC. The Utility of Anatomical Liver Resection in Hepatocellular Carcinoma: Associated with Improved Outcomes or Lack of Supportive Evidence? Cancers (Basel) 2019; 11:E1441. [PMID: 31561585 PMCID: PMC6826719 DOI: 10.3390/cancers11101441] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2019] [Revised: 09/19/2019] [Accepted: 09/24/2019] [Indexed: 01/27/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide. Surgical resection of HCC remains one of the mainstays of curative therapies and is associated with five-year overall survival rates approaching 60%. Despite improved perioperative outcomes, locoregional recurrence within the first two years following hepatic resection is of significant concern with recurrence rates of up to 50%. The use of anatomical resection surgical approaches, whereby the portal venous blood flow is ligated proximal to the tumor bed, is postulated to reduce recurrence rates due to reduction of micrometastatic disease. The aim of this review is to characterize the definition of an anatomical resection (AR) during partial hepatectomy, discuss the theoretical advantages of AR during hepatic resection for HCC, and to present evidence of the impact of AR on outcome measures in patients with HCC. Based on current data, there is a lack of conclusive evidence to support the universal use of AR in cirrhotic patients with HCC. A randomized clinical trial is warranted to further clarify the debate between AR versus non-anatomical resection (NAR) for HCC.
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Affiliation(s)
- Michelle Ju
- Department of Surgery, Division of Surgical Oncology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
| | - Adam C Yopp
- Department of Surgery, Division of Surgical Oncology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
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Oncological Outcomes of Hepatic Resection vs Transplantation for Localized Hepatocellular Carcinoma. Transplant Proc 2019; 51:1147-1152. [PMID: 31101189 DOI: 10.1016/j.transproceed.2019.01.093] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2018] [Accepted: 01/21/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND Scarce data are available comparing outcomes of hepatic resection vs orthotopic liver transplantation (OLT) for localized hepatocellular carcinoma (HCC) patients both meeting and exceeding the Milan criteria. This study compared the clinical and oncological outcomes of patients undergoing hepatic resection vs transplantation localized HCC. METHOD Between January 2005 and February 2017, clinical and oncological outcomes of patients who underwent liver resection (n = 38) vs OLT (n = 28) for localized HCC were compared using a prospectively maintained database. RESULTS A total of 66 patients (with a median age of 62) who met the study criteria were analyzed. Comparable postoperative complications (13.2% vs 28.6%, P = .45) and perioperative mortality rates (7.9% vs 10.7%, P = .2) were noted for the resection vs OLT groups. While Child-Pugh Class A patients were more prevalent in the resection group (78.9% vs 7.1%, P = .0001), the rate of patients who met the Milan criteria was higher in the OLT group (89.3% vs 34.25, P = .0001). Recurrence rates were 36.8% in the resection group and 3.6% in the OLT group at the end of the median follow-up period (32 vs 39 months, respectively). The HCC-related mortality rate was significantly higher in the resection group (39.5% vs 10.7%, P = .034). However, a subgroup analysis of patients who met the Milan criteria revealed similar rates of recurrence and HCC-related mortality (15.4% vs 8%, P = .63). Based on logistic regression analysis, number of tumors (P = .034, odds ratio: 2.1) and "resection"-type surgery (P = .008, odds ratio: 20.2) were independently associated with recurrence. CONCLUSION Compared to liver transplantation, hepatic resection for localized hepatocellular carcinoma is associated with a higher rate of recurrence and disease-related mortality.
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Kang KJ, Ahn KS. Privileged indication of anatomical resection for the hepatocellular carcinoma with microportal invasion? Transl Gastroenterol Hepatol 2019; 4:3. [PMID: 30854490 PMCID: PMC6378245 DOI: 10.21037/tgh.2018.12.10] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2018] [Accepted: 12/26/2018] [Indexed: 11/06/2022] Open
Affiliation(s)
- Koo Jeong Kang
- Division of Hepatobiliary & Pancreatic Surgery, Department of Surgery, Keimyung University, Dongsan Medical Center, Daegu, Republic of Korea
| | - Keun Soo Ahn
- Division of Hepatobiliary & Pancreatic Surgery, Department of Surgery, Keimyung University, Dongsan Medical Center, Daegu, Republic of Korea
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Ueda J, Yoshida H, Mamada Y, Taniai N, Yoshioka M, Hirakata A, Kawano Y, Shimizu T, Kanda T, Takata H, Uchida E. Evaluation of the Impact of Preoperative Values of Hyaluronic Acid and Type IV Collagen on the Outcome of Patients with Hepatocellular Carcinoma After Hepatectomy. J NIPPON MED SCH 2018; 85:221-227. [PMID: 30259891 DOI: 10.1272/jnms.jnms.2018_85-34] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
BACKGROUND Recently, some reports have revealed a relationship between post-hepatectomy prognosis in hepatocellular carcinoma (HCC) and hepatic fibrosis markers. We evaluated the relationship between these markers of hepatic fibrosis, clinicopathological findings, and prognosis. METHODS Three hundred and sixty patients underwent hepatectomy for HCC in the Nippon Medical School Hospital between 1993 and 2013. We divided these patients into two groups: normal serum hyaluronic acid (HA) levels and abnormal levels. We also divided patients into groups with normal serum type IV collagen levels and abnormal levels. RESULTS The overall survival rate and recurrence-free survival rate of the normal group were significantly higher than those of the abnormal group. In the normal hyaluronic acid group, serum albumin and prothrombin time were significantly higher than in the abnormal group, and age, hepatitis C virus antibody (HCV)-Ab positivity, Child-Pugh grade B, liver cirrhosis, indocyanine green retention rate at 15 min (ICGR15), type IV collagen level, and type IV collagen 7s level were significantly lower than those in the abnormal group. In the normal type IV collagen group, HCV-Ab positivity, liver cirrhosis, ICGR15, HA level, and type IV collagen 7s level were significantly lower than those in the abnormal group, and the serum albumin level was significantly higher than that in the abnormal group. Multivariate analysis independently revealed the significant effect of serum type IV collagen on the overall survival rate as well as the significant effect of serum HA on the recurrence-free survival rate in patients who underwent hepatectomy for HCC. CONCLUSIONS Preoperative examinations of serum hyaluronic acid levels and type IV collagen levels are imperative for hepatic resection for HCC because these markers are significantly associated with liver function and prognosis.
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Affiliation(s)
- Junji Ueda
- Department of Gastrointestinal Hepato-Biliary-Pancreatic Surgery, Nippon Medical School.,Department of Surgery, Nippon Medical School Tama Nagayama Hospital
| | - Hiroshi Yoshida
- Department of Gastrointestinal Hepato-Biliary-Pancreatic Surgery, Nippon Medical School
| | - Yasuhiro Mamada
- Department of Gastrointestinal Hepato-Biliary-Pancreatic Surgery, Nippon Medical School
| | - Nobuhiko Taniai
- Department of Gastrointestinal Hepato-Biliary-Pancreatic Surgery, Nippon Medical School
| | - Masato Yoshioka
- Department of Gastrointestinal Hepato-Biliary-Pancreatic Surgery, Nippon Medical School
| | - Atsushi Hirakata
- Department of Surgery, Nippon Medical School Tama Nagayama Hospital
| | - Youichi Kawano
- Department of Gastrointestinal Hepato-Biliary-Pancreatic Surgery, Nippon Medical School
| | - Tetsuya Shimizu
- Department of Gastrointestinal Hepato-Biliary-Pancreatic Surgery, Nippon Medical School
| | - Tomohiro Kanda
- Department of Gastrointestinal Hepato-Biliary-Pancreatic Surgery, Nippon Medical School
| | - Hideyuki Takata
- Department of Surgery, Nippon Medical School Tama Nagayama Hospital
| | - Eiji Uchida
- Department of Gastrointestinal Hepato-Biliary-Pancreatic Surgery, Nippon Medical School
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Famularo S, Di Sandro S, Giani A, Lauterio A, Sandini M, De Carlis R, Buscemi V, Romano F, Gianotti L, De Carlis L. Long-term oncologic results of anatomic vs. parenchyma-sparing resection for hepatocellular carcinoma. A propensity score-matching analysis. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2018; 44:1580-1587. [PMID: 29861336 DOI: 10.1016/j.ejso.2018.05.018] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2017] [Revised: 04/30/2018] [Accepted: 05/11/2018] [Indexed: 12/29/2022]
Abstract
PURPOSE The extent of liver resection for the optimal treatment of hepatocellular carcinoma (HCC) is debated. The purpose of this study was to compare the impact of anatomic resection (AR) vs. parenchyma-sparing resection (PSR) on disease recurrence and patient survival. METHODS We retrospectively analyzed patients with HCC who underwent liver resection from January 2001 to August 2015. Patients receiving AR or PSR were compared by a propensity score analysis (PSA) (caliper = 0.1). The primary outcomes were disease-free survival (DFS) and overall survival (OS) rates, and assessed by the Kaplan-Meier method. RESULTS 455 consecutive patients were evaluated. After PSA 354 patient were studied (177 pairs for each group). The median follow-up time was 28.2 months. The median OS was 47.5 months (95% CI: 30.0-65.9) for AR and 56.5 months (95% CI 33.2-79.6) for PSR (p = 0.169). The median DFS was 29.2 months (95% CI 17.6-40.8) for AR and 24.8 months (95% CI: 15.2-34.2) for PSR (p = 0.337). The multivariate regression model showed that cirrhosis (HR 2.85, 95% CI: 1.53-5.32; p = 0.001), BCLC grade B (HR 4.15, 95% CI: 1.33-12.95; p = 0.014), microvascular invasion (HR 1.55, 95% CI: 1.03-2.31; p = 0.033), presence of satellitosis (HR 1.94, 95% CI: 1.25-3.01; p = 0.003), severe complications (HR 6.09, 95% CI: 2.26-16.40; p > 0.001) were independently associated with poor long-term oncologic outcomes. CONCLUSIONS The extent of resection did not significantly affect overall and disease-free survival while tumor characteristics and underlying liver function appeared significant determinants.
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Affiliation(s)
- Simone Famularo
- School of Medicine and Surgery, University of Milan-Bicocca, Monza, Italy; Department of Surgery, San Gerardo Hospital, Monza, Italy
| | - Stefano Di Sandro
- Department of General Surgery and Transplantation, Ca'Granda Niguarda Hospital, Milan, Italy
| | - Alessandro Giani
- School of Medicine and Surgery, University of Milan-Bicocca, Monza, Italy; Department of Surgery, San Gerardo Hospital, Monza, Italy
| | - Andrea Lauterio
- Department of General Surgery and Transplantation, Ca'Granda Niguarda Hospital, Milan, Italy
| | - Marta Sandini
- School of Medicine and Surgery, University of Milan-Bicocca, Monza, Italy; Department of Surgery, San Gerardo Hospital, Monza, Italy
| | - Riccardo De Carlis
- Department of General Surgery and Transplantation, Ca'Granda Niguarda Hospital, Milan, Italy
| | - Vincenzo Buscemi
- Department of General Surgery and Transplantation, Ca'Granda Niguarda Hospital, Milan, Italy
| | - Fabrizio Romano
- School of Medicine and Surgery, University of Milan-Bicocca, Monza, Italy; Department of Surgery, San Gerardo Hospital, Monza, Italy
| | - Luca Gianotti
- School of Medicine and Surgery, University of Milan-Bicocca, Monza, Italy; Department of Surgery, San Gerardo Hospital, Monza, Italy.
| | - Luciano De Carlis
- School of Medicine and Surgery, University of Milan-Bicocca, Monza, Italy; Department of General Surgery and Transplantation, Ca'Granda Niguarda Hospital, Milan, Italy
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Song T, Wang C, Guo C, Liu Q, Zheng X. Pentraxin 3 overexpression accelerated tumor metastasis and indicated poor prognosis in hepatocellular carcinoma via driving epithelial-mesenchymal transition. J Cancer 2018; 9:2650-2658. [PMID: 30087705 PMCID: PMC6072810 DOI: 10.7150/jca.25188] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2018] [Accepted: 05/08/2018] [Indexed: 12/13/2022] Open
Abstract
As a pattern recognition receptor, pentraxin 3 (PTX3) has been found to exert the pleiotropic roles on a variety of cancers. However, the accurate clinical significance of PTX3 in hepatocellular carcinoma (HCC) has not been well defined. The aim of the present investigation was to determine the expression characteristics, prognostic significance, and the relevant biological effect of PTX3 in HCC. The expression of PTX3 was evaluated in tumor and adjacent liver tissues from 210 HCC patients using immunohistochemistry staining. And it was found that a marked up-regulation in the expression of PTX3 in the HCC specimens, which was remarkably correlated with high serum AFP level (P = 0.006), larger tumor size (P <0.001), liver cirrhosis (P = 0.004), advanced TNM stage (P = 0.022), PVTT (P = 0.010), intra-hepatic metastases (P = 0.019), and MVI (P <0.001). PTX3 was identified as an independent predictive factor of poor prognosis by multivariate analysis. Ectopic expression of PTX3 enhanced proliferation, migration, invasion capacities of Huh7 cells and induced EMT phenotype. Silencing PTX3 obtained the opposite results. Moreover, the in vivo experiments confirmed PTX3 induced EMT and promoted proliferation and growth of HCC cells. Collectivelly, these data indicated that PTX3 could accelerate HCC progression through activating EMT and served as a potential predictive factor and therapeutic target for HCC.
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Affiliation(s)
- Tao Song
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China
| | - Cong Wang
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China
| | - Cheng Guo
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China
| | - Qingguang Liu
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China
| | - Xin Zheng
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China
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Kang WH, Kim KH, Jung DH, Park GC, Kim SH, Cho HD, Lee SG. Long-term results of laparoscopic liver resection for the primary treatment of hepatocellular carcinoma: role of the surgeon in anatomical resection. Surg Endosc 2018; 32:4481-4490. [PMID: 29691651 DOI: 10.1007/s00464-018-6194-0] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2017] [Accepted: 04/20/2018] [Indexed: 12/22/2022]
Abstract
BACKGROUND Liver resection is a potentially curative therapy for hepatocellular carcinoma (HCC). LLR is a newly developed and safe technique associated with shorter hospital stay, less pain, better cosmetic outcomes, and similar complication rates as open surgery; however, data on its long-term outcomes remain scarce. METHODS We retrospectively examined the clinical and follow-up data of 234 patients who underwent LLR (performed by a single surgeon in all cases) for the primary treatment of HCC between July 2007 and December 2015 at Asan Medical Center. RESULTS The mean patient age was 55.63 (range 31-76) years; 167 were men. The median follow-up duration was 38 (range 6-116) months. A total of 227 patients (97.0%) had Child-Turcotte-Pugh grade A disease. Of them, 167 (71.4%) underwent anatomical resections and 63 (28.6%) underwent non-anatomical partial hepatectomies. Overall survival rates were 98.3, 91.7, and 87.1%, and recurrence-free survival rates were 82.1, 67.5, and 55.3% at 1, 3, and 5 years, respectively. In Cox regression analysis, anatomical resection was a risk factor for recurrence (univariate analysis: hazard ratio [HR] 0.49; 95% confidence interval [CI] 0.31-0.75; p = 0.001; multivariate analysis: HR 0.59; 95% CI 0.38-0.94; p = 0.025). CONCLUSIONS LLR is an acceptable primary treatment for patients with HCC with good hepatic function and with an appropriate anatomical structure, and is associated with improved prognosis. LLR can achieve lower recurrence rates through anatomical resection.
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Affiliation(s)
- Woo-Hyoung Kang
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Ki-Hun Kim
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.
| | - Dong-Hwan Jung
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Gil-Chun Park
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Seok-Hwan Kim
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Hwui-Dong Cho
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Sung-Gyu Lee
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
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Lee W, Han HS, Ahn S, Yoon YS, Cho JY, Choi Y. Correlation between Resection Margin and Disease Recurrence with a Restricted Cubic Spline Model in Patients with Resected Hepatocellular Carcinoma. Dig Surg 2018; 35:520-531. [PMID: 29342456 DOI: 10.1159/000485805] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2016] [Accepted: 11/27/2017] [Indexed: 12/31/2022]
Abstract
BACKGROUND The relationship between resection margin (RM) and recurrence of resected hepatocellular carcinoma (HCC) is unclear. METHODS We reviewed clinical data for 419 patients with HCC. The oncologic outcomes were compared between 2 groups of patients classified according to the inflexion point of the restricted cubic spline plot. RESULTS The patients were divided according to an RM of <1 cm (n = 233; narrow RM group) or ≥1 cm (n = 186; wide RM group). The 5-year recurrence-free survival (RFS) rate was lower (34.8 vs. 43.8%, p = 0.042) and recurrence near the resection site was more frequent (4.7 vs. 0%, p = 0.010) in the narrow RM group. Patients with multiple lesions, or prior transarterial chemoembolization (TACE) or radiofrequency ablation (RFA) were excluded from subgroup analyses. In patients with a 2-5 cm HCC, the 5-year RFS was greater in the wide RM group (54.4 vs. 32.5%, p = 0.036). Narrow RM (hazard ratio 1.750, 95% CI 1.029-2.976, p = 0.039) was independently associated with disease recurrence. CONCLUSION In patients with a single 2-5 cm HCC without prior TACE/RFA, an RM of ≥1 cm was associated with lower risk of recurrence after liver resection.
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Affiliation(s)
- Woohyung Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea.,Department of Surgery, Gyeongsang National University Changwon Hospital, Gyeongsang National University College of Medicine, Changwong-si, Republic of Korea
| | - Ho-Seong Han
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
| | - Soyeon Ahn
- Medical Research Collaborating Center, Seoul National University Bundang Hospital, Seoul National University, Seongnam, Republic of Korea
| | - Yoo-Seok Yoon
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
| | - Jai Young Cho
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
| | - YoungRok Choi
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
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Xu H, Liu F, Li H, Wei Y, Li B. Outcomes following laparoscopic versus open major hepatectomy: a meta-analysis. Scand J Gastroenterol 2017; 52:1307-1314. [PMID: 28880729 DOI: 10.1080/00365521.2017.1373846] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
OBJECTIVE The role of laparoscopic major hepatectomy (LMH) remains uncertain in current liver surgery. This meta-analysis aimed to compare surgical and oncological outcomes of LMH versus open major hepatectomy (OMH). METHODS A systematic search was conducted in PubMed, Embase, and the Cochrane Library database to identify all relevant publications. The statistical analysis was performed using Review Manager version 5.3. Continuous variables were calculated by standardized mean differences (SMD) with 95% confidence interval (CI), whereas dichotomous variables were calculated by odds ratio (OR) with 95%CI. RESULTS A total of 10 eligible studies with 1130 patients were identified, of which 455 (40.3%) patients in the LMH group and 675 (59.7%) patients in the OMH group. LMH was associated with less blood loss (SMD = -0.30, 95%CI: -0.43 to -0.18, p < .00001), less transfusion requirement (OR = 0.49, 95%CI: 0.29-0.82, p = .007), decreased postoperative morbidity (OR = 0.56, 95%CI: 0.42-0.76, p = .0001), and shorter hospital stay (SMD = -0.46, 95%CI: -0.69 to -0.24, p < .0001) when compared with the OMH group. But the operative time was significantly longer in LMH group (SMD = 0.61, 95%CI: 0.79-1.86, p = .01). Both the two groups achieved similar surgical margin and R0 resection rate for malignant lesions. CONCLUSIONS This meta-analysis demonstrated that LMH appeared to be feasible and safe in current liver surgery. LMH is associated with less blood loss, decreased postoperative morbidity, shorter hospital stay, and comparable oncological outcomes compared with OMH.
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Affiliation(s)
- Hongwei Xu
- a Department of Liver Surgery , Center of Liver Transplantation , Chengdu , Sichuan Province , China
| | - Fei Liu
- a Department of Liver Surgery , Center of Liver Transplantation , Chengdu , Sichuan Province , China
| | - Hongyu Li
- b Department of Pancreatic Surgery , West China Hospital of Sichuan University , Chengdu , Sichuan Province , China
| | - Yonggang Wei
- a Department of Liver Surgery , Center of Liver Transplantation , Chengdu , Sichuan Province , China
| | - Bo Li
- a Department of Liver Surgery , Center of Liver Transplantation , Chengdu , Sichuan Province , China
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Christ B, Dahmen U, Herrmann KH, König M, Reichenbach JR, Ricken T, Schleicher J, Ole Schwen L, Vlaic S, Waschinsky N. Computational Modeling in Liver Surgery. Front Physiol 2017; 8:906. [PMID: 29249974 PMCID: PMC5715340 DOI: 10.3389/fphys.2017.00906] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2017] [Accepted: 10/25/2017] [Indexed: 12/13/2022] Open
Abstract
The need for extended liver resection is increasing due to the growing incidence of liver tumors in aging societies. Individualized surgical planning is the key for identifying the optimal resection strategy and to minimize the risk of postoperative liver failure and tumor recurrence. Current computational tools provide virtual planning of liver resection by taking into account the spatial relationship between the tumor and the hepatic vascular trees, as well as the size of the future liver remnant. However, size and function of the liver are not necessarily equivalent. Hence, determining the future liver volume might misestimate the future liver function, especially in cases of hepatic comorbidities such as hepatic steatosis. A systems medicine approach could be applied, including biological, medical, and surgical aspects, by integrating all available anatomical and functional information of the individual patient. Such an approach holds promise for better prediction of postoperative liver function and hence improved risk assessment. This review provides an overview of mathematical models related to the liver and its function and explores their potential relevance for computational liver surgery. We first summarize key facts of hepatic anatomy, physiology, and pathology relevant for hepatic surgery, followed by a description of the computational tools currently used in liver surgical planning. Then we present selected state-of-the-art computational liver models potentially useful to support liver surgery. Finally, we discuss the main challenges that will need to be addressed when developing advanced computational planning tools in the context of liver surgery.
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Affiliation(s)
- Bruno Christ
- Molecular Hepatology Lab, Clinics of Visceral, Transplantation, Thoracic and Vascular Surgery, University Hospital Leipzig, University of Leipzig, Leipzig, Germany
| | - Uta Dahmen
- Experimental Transplantation Surgery, Department of General, Visceral and Vascular Surgery, University Hospital Jena, Jena, Germany
| | - Karl-Heinz Herrmann
- Medical Physics Group, Institute for Diagnostic and Interventional Radiology, University Hospital Jena, Friedrich Schiller University Jena, Jena, Germany
| | - Matthias König
- Department of Biology, Institute for Theoretical Biology, Humboldt University of Berlin, Berlin, Germany
| | - Jürgen R Reichenbach
- Medical Physics Group, Institute for Diagnostic and Interventional Radiology, University Hospital Jena, Friedrich Schiller University Jena, Jena, Germany
| | - Tim Ricken
- Mechanics, Structural Analysis, and Dynamics, TU Dortmund University, Dortmund, Germany
| | - Jana Schleicher
- Experimental Transplantation Surgery, Department of General, Visceral and Vascular Surgery, University Hospital Jena, Jena, Germany.,Department of Bioinformatics, Friedrich Schiller University Jena, Jena, Germany
| | | | - Sebastian Vlaic
- Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Jena, Germany
| | - Navina Waschinsky
- Mechanics, Structural Analysis, and Dynamics, TU Dortmund University, Dortmund, Germany
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Görtz M, Galli U, Longerich T, Zöller M, Erb U, Schemmer P. De novo synthesis of C4.4A in hepatocellular carcinoma promotes migration and invasion of tumor cells. Oncol Rep 2017; 38:2697-2704. [PMID: 29048672 PMCID: PMC5780022 DOI: 10.3892/or.2017.5980] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2017] [Accepted: 08/31/2017] [Indexed: 01/12/2023] Open
Abstract
C4.4A is a glycoprotein that is upregulated in several human malignancies, including colorectal, breast and renal cell carcinomas. Due to its highly restricted expression in healthy tissue, C4.4A was proposed as a potential diagnostic marker. Thus, the present study was designed to evaluate C4.4A expression and function in hepatocellular carcinoma (HCC) for the first time. Immunohistochemistry was performed to detect expression of C4.4A in human sections of healthy liver, primary HCC in the liver and metastatic HCC in the lung. To assess the contribution of C4.4A to HCC progression proliferation, apoptosis, migration and invasion assays were performed with C4.4A knockdown Huh7 and HepG2 cells. C4.4A is absent in healthy liver tissue. However, intense expression was seen in 59% of primary HCCs and strong expression in 80% of HCC lung metastases. C4.4A expression was also observed in human HCC cell lines, which strongly increased under hypoxic conditions. A C4.4A knock-down revealed that C4.4A is involved in both migration and invasion of HCC cells. Taken together, C4.4A expression in both primary and metastatic HCC suggests its potential value as a diagnostic marker for HCC. Due to its absence in healthy liver tissue, C4.4A might even serve as a possible therapeutic target, particularly for metastatic HCC.
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Affiliation(s)
- Magdalena Görtz
- Department of General and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Uwe Galli
- Department of General and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Thomas Longerich
- Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany
| | - Margot Zöller
- Tumor Cell Biology, Department of General and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Ulrike Erb
- Tumor Cell Biology, Department of General and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Peter Schemmer
- Department of General and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
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Ling N, Zhou X, Ji Y, Li W, Ji C, Qi Z. Immuno-modulatory and cellular antioxidant activities of κ-selenocarrageenan in combination with Epirubicin in H22 hepatoma-bearing mice. Biomed Pharmacother 2017; 91:132-137. [PMID: 28448867 DOI: 10.1016/j.biopha.2017.04.064] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2016] [Revised: 03/15/2017] [Accepted: 04/13/2017] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Human hepatocellular carcinoma (HCC) has a high rate of tumor recurrence and metastasis, resulting in shortened survival time. The aim of this study is to evaluate the synergistic anti-tumor effects and underlying mechanism of κ-selenocarrageenan (KSC) in combination with the chemotherapy drug epirubicin (EPI) in H22 tumor-bearing mice. METHODS Hepatocellular carcinoma H22 cells were implanted into mice. After the transplants were successfully established, the animals were divided into four groups: namely the control group, the KSC group, the EPI group and the KSC+EPI group. The effects of KSC and EPI on tumor growth, survival time, thymus index, spleen index, white blood cells (WBC), splenocyte proliferation, natural killer (NK) cell activity, serum TNF-α and IL-2 levels, and antioxidant enzymes in the liver cells were determined. RESULTS KSC and/or EPI significantly reduced tumor weight and prolonged the survival time. Furthermore, KSC could attenuate EPI-induced atrophy in the thymus and spleen, as well as other toxicities, which may indicate an additive effect of this combination against organ dysfunction and cellular injury. KSC significantly promoted Con A- and LPS-stimulated splenocyte proliferation, enhanced NK cell activity, and reversed the inhibition of NK activity induced by EPI (P<0.01). In addition, KSC could elevate serum TNF-α and IL-2 levels, increase the GSH-Px, SOD, CAT and GSH activity levels in liver tissue, and reduce MDA content. CONCLUSIONS These results suggest that KSC can regulate immune function in mice and suppress the growth of tumor in H22 tumor-bearing mice, and its synergistic antitumor activity with epirubicin may be related to its antioxidant and immuno-modulatory effects.
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Affiliation(s)
- Na Ling
- College of Science, Harbin University of Commerce, Harbin 150076, Heilongjiang Province, China.
| | - Xiaojun Zhou
- College of Life Science, Luoyang Normal University, Luoyang 471022, Henan Province, China.
| | - Yubin Ji
- College of Science, Harbin University of Commerce, Harbin 150076, Heilongjiang Province, China
| | - Wenlan Li
- College of Science, Harbin University of Commerce, Harbin 150076, Heilongjiang Province, China
| | - Chenfeng Ji
- College of Science, Harbin University of Commerce, Harbin 150076, Heilongjiang Province, China
| | - Zheng Qi
- College of Science, Harbin University of Commerce, Harbin 150076, Heilongjiang Province, China
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