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1
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Cai Y, Wang W, Jiao Q, Hu T, Ren Y, Su X, Li Z, Feng M, Liu X, Wang Y. Nanotechnology for the Diagnosis and Treatment of Liver Cancer. Int J Nanomedicine 2024; 19:13805-13821. [PMID: 39735328 PMCID: PMC11681781 DOI: 10.2147/ijn.s490661] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Accepted: 12/04/2024] [Indexed: 12/31/2024] Open
Abstract
Liver cancer has become a major global health challenge due to its high incidence, high rate of late diagnosis and limited treatment options. Although there are many clinical treatments available for liver cancer, the cure rate is still very low, and now researchers have begun to explore new aspects of liver cancer treatment, and nanotechnology has shown great potential for improving diagnostic accuracy and therapeutic efficacy and is therefore a promising treatment option. In diagnosis, nanomaterials such as gold nanoparticles, magnetic nanoparticles, and silver nanoparticles can realize highly sensitive and specific detection of liver cancer biomarkers, supporting diagnosis and real-time monitoring of the disease process. In terms of treatment, nanocarriers can realize precise targeted delivery of drugs, improve the bioavailability of liver cancer therapeutic drugs and reduce systemic toxic side effects. In addition, advanced technologies such as nanoparticle-based photothermal therapy and photodynamic therapy provide innovative solutions to overcome drug resistance and local tumor ablation. Therefore, in this paper, we will introduce nanotechnology for hepatocellular carcinoma in terms of tumor marker detection, targeted drug delivery, and synergistic PDT/CDT therapy.
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Affiliation(s)
- Yuxuan Cai
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China
| | - Weiwei Wang
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China
| | - Qinlian Jiao
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China
| | - Tangbin Hu
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China
| | - Yidan Ren
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China
| | - Xin Su
- Department of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250033, People’s Republic of China
| | - Zigan Li
- Department of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250033, People’s Republic of China
| | - Maoxiao Feng
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China
| | - Xiaoyan Liu
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China
| | - Yunshan Wang
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China
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Lee JS, Choi HW, Kim JS, Lee TY, Yoon YC. Update on Resection Strategies for Hepatocellular Carcinoma: A Narrative Review. Cancers (Basel) 2024; 16:4093. [PMID: 39682279 DOI: 10.3390/cancers16234093] [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: 11/12/2024] [Accepted: 12/03/2024] [Indexed: 12/18/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver cancer, the incidence of which is rising globally. Despite recent advancements in immunotherapeutic and surgical treatment modalities, the prognosis for HCC remains poor. The surgical treatment strategy for HCC comprises a multimodal effort that ranges from ablative therapy and surgical resection to liver transplantation. Thanks to collective efforts from the surgical society, there have been rapid advances in resection strategies, such as 3D printing for surgical planning and minimally invasive techniques to minimize surgical trauma. This review examines recent advancements in surgical techniques, patient selection criteria, and perioperative management for HCC resection. The purpose of this review was to provide clinicians and researchers with an up-to-date perspective on the evolving role of surgical resection in HCC treatment, and to identify key areas for future investigation to improve patient outcomes.
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Affiliation(s)
- Jun Suh Lee
- Department of Surgery, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
| | - Hyeong Woo Choi
- Department of Surgery, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
| | - Ji Su Kim
- Department of Surgery, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
| | - Tae Yoon Lee
- Department of Surgery, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
| | - Young Chul Yoon
- Department of Surgery, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
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Wang T, Chen H, Chen Z, Li M, Lu Y. Prediction model of early recurrence of multimodal hepatocellular carcinoma with tensor fusion. Phys Med Biol 2024; 69:125003. [PMID: 38776945 DOI: 10.1088/1361-6560/ad4f45] [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: 12/24/2023] [Accepted: 05/22/2024] [Indexed: 05/25/2024]
Abstract
Objective.In oncology, clinical decision-making relies on a multitude of data modalities, including histopathological, radiological, and clinical factors. Despite the emergence of computer-aided multimodal decision-making systems for predicting hepatocellular carcinoma (HCC) recurrence post-hepatectomy, existing models often employ simplistic feature-level concatenation, leading to redundancy and suboptimal performance. Moreover, these models frequently lack effective integration with clinically relevant data and encounter challenges in integrating diverse scales and dimensions, as well as incorporating the liver background, which holds clinical significance but has been previously overlooked.Approach.To address these limitations, we propose two approaches. Firstly, we introduce the tensor fusion method to our model, which offers distinct advantages in handling multi-scale and multi-dimensional data fusion, potentially enhancing overall performance. Secondly, we pioneer the consideration of the liver background's impact, integrating it into the feature extraction process using a deep learning segmentation-based algorithm. This innovative inclusion aligns the model more closely with real-world clinical scenarios, as the liver background may contain crucial information related to postoperative recurrence.Main results.We collected radiomics (MRI) and histopathological images from 176 cases diagnosed by experienced clinicians across two independent centers. Our proposed network underwent training and 5-fold cross-validation on this dataset before validation on an external test dataset comprising 40 cases. Ultimately, our model demonstrated outstanding performance in predicting early recurrence of HCC postoperatively, achieving an AUC of 0.883.Significance.These findings signify significant progress in addressing challenges related to multimodal data fusion and hold promise for more accurate clinical outcome predictions. In this study, we exploited global 3D liver background into modelling which is crucial to to the prognosis assessment and analyzed the whole liver background in addition to the tumor region. Both MRI images and histopathological images of HCC were fused at high-dimensional feature space using tensor techniques to solve cross-scale data integration issue.
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Affiliation(s)
- Tianyi Wang
- School of Computer Science and Engineering, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Haimei Chen
- Department of Radiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Zebin Chen
- Department of Liver Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Mingkai Li
- Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Yao Lu
- School of Computer Science and Engineering, Sun Yat-sen University, Guangzhou, People's Republic of China
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Wang J, Im Y, Wang R, Ma S. Partial Hepatectomy and Ablation for Survival of Early-Stage Hepatocellular Carcinoma Patients: A Bayesian Emulation Analysis. Life (Basel) 2024; 14:661. [PMID: 38929645 PMCID: PMC11204969 DOI: 10.3390/life14060661] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2024] [Revised: 05/19/2024] [Accepted: 05/21/2024] [Indexed: 06/28/2024] Open
Abstract
Partial hepatectomy and ablation therapy are two widely used surgical procedures for localized early-stage hepatocellular carcinoma (HCC) patients. This article aimed to evaluate their relative effectiveness in terms of overall survival. An emulation analysis approach was first developed based on the Bayesian technique. We estimated propensity scores via Bayesian logistic regression and adopted a weighted Bayesian Weibull accelerated failure time (AFT) model incorporating prior information contained in the published literature. With the Surveillance, Epidemiology, and End Results (SEER)-Medicare data, an emulated target trial with rigorously defined inclusion/exclusion criteria and treatment regimens for early-stage HCC patients over 66 years old was developed. For the main cohort with tumor size less than or equal to 5 cm, a total of 1146 patients were enrolled in the emulated trial, with 301 and 845 in the partial hepatectomy and ablation arms, respectively. The analysis suggested ablation to be significantly associated with inferior overall survival (hazard ratio [HR] = 1.35; 95% credible interval [CrI]: 1.14, 1.60). For the subgroup with tumor size less than or equal to 3 cm, there was no significant difference in overall survival between the two arms (HR = 1.15; 95% CrI: 0.88, 1.52). Overall, the comparative treatment effect of ablation and partial hepatectomy on survival remains inconclusive. This finding may provide further insight into HCC clinical treatment.
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Affiliation(s)
- Jiping Wang
- Department of Biostatistics, Yale School of Public Health, New Haven, CT 06510, USA;
| | - Yunju Im
- Department of Biostatistics, University of Nebraska Medical Center (UNMC), Omaha, NE 68198, USA;
| | - Rong Wang
- Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT 06510, USA;
- Yale Cancer Outcomes, Public Policy and Effectiveness Research (COPPER) Center, New Haven, CT 06520, USA
| | - Shuangge Ma
- Department of Biostatistics, Yale School of Public Health, New Haven, CT 06510, USA;
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Zhang C, An S, Lv R, Li K, Liu H, Li J, Tang Y, Cai Z, Huang T, Long L, Deng W. The dynamic variation position and predominant quasispecies of hepatitis B virus: Novel predictors of early hepatocarcinoma. Virus Res 2024; 341:199317. [PMID: 38242020 PMCID: PMC10831745 DOI: 10.1016/j.virusres.2024.199317] [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: 11/13/2023] [Revised: 01/03/2024] [Accepted: 01/10/2024] [Indexed: 01/21/2024]
Abstract
To find the predictors of early HCC based on the dynamic changes of HBV quasispecies, this study utilizing the second-generation sequencing (NGS) and high-order multiplex droplet digital PCR (ddPCR) technology to examine the HBV quasispecies in serum of total 247 subjects recruited from high-incidence area of HCC. In the discovery stage, 15 non-synonymous Single Nucleotide Polymorphisms (SNPs) with higher variant proportion in HCC case group were founded (all P<0.05). Furthermore, the variant proportions in some of these SNPs were observed changing regularly within 5 years before the onset of HCC, and 5 of them located in HBX, 2 in HBS and 2 in HBC. The HBV predominant quasispecies and their consensus sequences were identified by genetic evolution analysis, in which the high HBS and HBC quasispecies heterogeneity were found associated with the forming of multifarious quasispecies clones, and the HBX gene had the highest proportion of predominant quasispecies (46.7 % in HBX vs 12.7 % and 13.8 % in HBS and HBC respectively) with the key variations (G1512A, A1630G, T1753C/G/A, A1762T and G1764A) determined. In the validation stage, we confirmed that the combined double mutations of G1512A+A1630G, A1762T+G1764A, and the combined triple mutations of T1753C/G/A + A1762T+G1764A, all expressed higher in early HCC cases when comparing with control group (all P<0.05). We also demonstrated the advantages of ddPCR using in multi-variations detection in large-sample for early HCC surveillance and screening. So we think that the dynamic of key HBV variation positions and their different combinations determined by quasispecies anlysis in this study can act as the novel predictors of early hepatocarcinoma and suitable to popularize and apply in HCC screening.
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Affiliation(s)
- Chaojun Zhang
- Department of experimental research, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Sanchun An
- Department of experimental research, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Ruibo Lv
- Department of experimental research, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Kezhi Li
- Department of experimental research, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China; Guangxi Cancer Molecular Medicine Engineering Research Center, China
| | - Haizhou Liu
- Department of experimental research, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China; Guangxi Cancer Molecular Medicine Engineering Research Center, China
| | - Jilin Li
- Department of experimental research, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China; Guangxi Cancer Molecular Medicine Engineering Research Center, China
| | - Yanping Tang
- Department of experimental research, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China; Guangxi Cancer Molecular Medicine Engineering Research Center, China
| | - Zhengmin Cai
- Department of experimental research, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China; Guangxi Cancer Molecular Medicine Engineering Research Center, China
| | - Tianren Huang
- Department of experimental research, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China; Guangxi Cancer Molecular Medicine Engineering Research Center, China.
| | - Long Long
- Big data College of Nanning normal University, Nanning, Guangxi 530100, China.
| | - Wei Deng
- Department of experimental research, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China; Guangxi Cancer Molecular Medicine Engineering Research Center, China.
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Huang K, He Y, Liang T, Mo S, Liao Y, Gao Q, Liao X, Han C, Zhu G, Peng T. Analysis of clinicopathologic and imaging features of dual-phenotype hepatocellular carcinoma. Sci Rep 2024; 14:3314. [PMID: 38332165 PMCID: PMC10853567 DOI: 10.1038/s41598-024-53831-5] [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: 09/01/2023] [Accepted: 02/05/2024] [Indexed: 02/10/2024] Open
Abstract
Dual-phenotype hepatocellular carcinoma (DPHCC) is a new subtype of hepatocellular carcinoma (HCC). This study aimed to investigate the relationship between the computerized tomography scan (CT) imaging and clinicopathologic features of DPHCC. The CT imaging and clinicopathologic data of 97 HCC cases who underwent radical resection were collected retrospectively. The CT imaging feature was evaluated by the ratio of the average CT value of tumor to liver (TLR) in the plain scan, arterial, portal vein and delayed phases. The association between CT imaging and clinicopathologic features was analyzed using the t-test or chi-square test. Univariate and multivariate recurrence-free survival (RFS) analysis and overall survival (OS) were performed. The positive rates of cytokeratin 7 (CK7) and CK19 were 35.1% and 20.6% respectively. The positive rate of CK19 was significantly higher in cases with age < 47 years (P = 0.005), tumor diameter > 4 cm (P = 0.016) or AFP ≥ 400 ng/ml (P = 0.007). The TLR in the portal vein phase was significantly lower in CK19 positive group (P = 0.024). The recurrence risk was significantly higher in cases with CK19 positive (HR: 2.17, 95% CI 1.16 to 4.04, P = 0.013), tumor diameter > 4 cm (HR: 2.05, 95% CI 1.11 to 3.78, P = 0.019), AFP ≥ 400 ng/ml (HR: 2.50, 95% CI 1.37 to 4.54, P = 0.002) or CA199 ≥ 37 U/ml (HR: 2.23, 95% CI 1.12 to 4.42, P = 0.020). However, imaging features, pathological subtype, CK7 or CK19 expression were not significantly related to HCC OS in the univariate and multivariate analysis (all P > 0.05). The expression of CK19 may be associated with the enhancement feature of the portal vein phase CT image, and CK19 positive may suggest a worse RFS.
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Affiliation(s)
- Ketuan Huang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Shuang-Yong Rd. 6, Nanning, 530021, Guangxi Zhuang Autonomous Region, People's Republic of China
- Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Nanning, Guangxi Zhuang Autonomous Region, People's Republic of China
| | - Yongfei He
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Shuang-Yong Rd. 6, Nanning, 530021, Guangxi Zhuang Autonomous Region, People's Republic of China
- Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Nanning, Guangxi Zhuang Autonomous Region, People's Republic of China
| | - Tianyi Liang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Shuang-Yong Rd. 6, Nanning, 530021, Guangxi Zhuang Autonomous Region, People's Republic of China
- Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Nanning, Guangxi Zhuang Autonomous Region, People's Republic of China
| | - Shutian Mo
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Shuang-Yong Rd. 6, Nanning, 530021, Guangxi Zhuang Autonomous Region, People's Republic of China
- Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Nanning, Guangxi Zhuang Autonomous Region, People's Republic of China
| | - Yuan Liao
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Shuang-Yong Rd. 6, Nanning, 530021, Guangxi Zhuang Autonomous Region, People's Republic of China
- Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Nanning, Guangxi Zhuang Autonomous Region, People's Republic of China
| | - Qiang Gao
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Shuang-Yong Rd. 6, Nanning, 530021, Guangxi Zhuang Autonomous Region, People's Republic of China
- Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Nanning, Guangxi Zhuang Autonomous Region, People's Republic of China
| | - Xiwen Liao
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Shuang-Yong Rd. 6, Nanning, 530021, Guangxi Zhuang Autonomous Region, People's Republic of China
- Guangxi Key Laboratory of Enhanced Recovery After Surgery for Gastrointestinal Cancer, Nanning, Guangxi Zhuang Autonomous Region, People's Republic of China
| | - Chuangye Han
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Shuang-Yong Rd. 6, Nanning, 530021, Guangxi Zhuang Autonomous Region, People's Republic of China
- Guangxi Key Laboratory of Enhanced Recovery After Surgery for Gastrointestinal Cancer, Nanning, Guangxi Zhuang Autonomous Region, People's Republic of China
| | - Guangzhi Zhu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Shuang-Yong Rd. 6, Nanning, 530021, Guangxi Zhuang Autonomous Region, People's Republic of China
- Guangxi Key Laboratory of Enhanced Recovery After Surgery for Gastrointestinal Cancer, Nanning, Guangxi Zhuang Autonomous Region, People's Republic of China
| | - Tao Peng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Shuang-Yong Rd. 6, Nanning, 530021, Guangxi Zhuang Autonomous Region, People's Republic of China.
- Guangxi Key Laboratory of Enhanced Recovery After Surgery for Gastrointestinal Cancer, Nanning, Guangxi Zhuang Autonomous Region, People's Republic of China.
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Ziogas IA, Gleisner AL. Resection Versus Transplant for Hepatocellular Carcinoma: How to Offer the Best Modality. Surg Clin North Am 2024; 104:113-127. [PMID: 37953031 DOI: 10.1016/j.suc.2023.08.005] [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: 11/14/2023]
Abstract
Liver resection and liver transplantation are the mainstay of treatment for patients with hepatocellular carcinoma. Patient comorbidities, tumor resectability, and perioperative morbidity and mortality risk, specifically of post-hepatectomy liver failure, are determining factors when deciding between liver resection and liver transplantation in patients who do not have an obvious contraindication to either treatment. Liver resection is preferred in patients without cirrhosis, and it may be a reasonable choice in patient with cirrhosis but preserved liver function and no portal hypertension if the size and function of the future liver remnant are appropriate, especially if organ availability is scarce.
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Affiliation(s)
- Ioannis A Ziogas
- Department of Surgery, University of Colorado Anschutz Medical Campus, 12631 East 17th Avenue, Aurora, CO 80045, USA. https://twitter.com/IA_Ziogas
| | - Ana L Gleisner
- Department of Surgery, University of Colorado Anschutz Medical Campus, 12631 East 17th Avenue, Aurora, CO 80045, USA.
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Ni HH, Lu Z, Yang CL, Lv YT, Lu CX, Xiang BD. Clonorchis sinensis on the prognosis of patients with spontaneous rupture of Hepatocellular Carcinoma: An inverse probability of treatment weighting analysis. PLoS Negl Trop Dis 2024; 18:e0011987. [PMID: 38381766 PMCID: PMC10911612 DOI: 10.1371/journal.pntd.0011987] [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: 07/31/2023] [Revised: 03/04/2024] [Accepted: 02/12/2024] [Indexed: 02/23/2024] Open
Abstract
BACKGROUND We examined the impact of the Clonorchis sinensis (C. sinensis) infection on the survival outcomes of spontaneous rupture Hepatocellular Carcinoma (srHCC) patients undergoing hepatectomy. METHODS Between May 2013 and December 2021, 157 consecutive srHCC patients who underwent hepatectomy were divided into an no C. sinensis group (n = 126) and C. sinensis group (n = 31). To adjust for differences in preoperative characteristics an inverse probability of treatment weighting (IPTW) analysis was done, using propensity scores. Overall survival (OS) and recurrence-free survival (RFS) were compared before and after IPTW. Multivariate Cox regression analysis was performed to determine whether the C. sinensis infection was an independent prognostic factor after IPTW. RESULTS In original cohort, the no C. sinensis group did not show a survival advantage over the C. sinensis group. After IPTW adjustment, the median OS for the C. sinensis group was 9 months, compared to 29 months for the no C. sinensis group. C. sinensis group have worse OS than no C. sinensis group (p = 0.024), while it did not differ in RFS(p = 0.065). The multivariate Cox regression analysis showed that C. sinensis infection and lower age were associated with worse OS. CONCLUSIONS The C. sinensis infection has an adverse impact on os in srHCC patients who underwent hepatectomy.
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Affiliation(s)
- Hang-Hang Ni
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China
- Department of Hepatobiliary Surgery, Zhongshan City People’s Hospital, Zhongshan, People’s Republic of China
| | - Zhan Lu
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China
| | - Cheng-Lei Yang
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China
| | - Yu-Ting Lv
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China
| | - Chun-Xiu Lu
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China
| | - Bang-De Xiang
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China
- Key Laboratory of Early Prevention and Treatment for Regional High-Frequency Tumors, Ministry of Education, Nanning, People’s Republic of China
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9
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Pan B, Wang Z, Chen R, Zhang X, Qiu J, Wu X, Yao Y, Luo Y, Wang X, Tang N. Single-cell atlas reveals characteristic changes in intrahepatic HBV-specific leukocytes. Microbiol Spectr 2024; 12:e0286023. [PMID: 38032223 PMCID: PMC10782979 DOI: 10.1128/spectrum.02860-23] [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: 07/17/2023] [Accepted: 11/01/2023] [Indexed: 12/01/2023] Open
Abstract
IMPORTANCE Hepatitis B virus (HBV)-specific CD8+ T cells play a central role in the clearance of virus and HBV-related liver injury. Acute infection with HBV induces a vigorous, multifunctional CD8+ T cell response, whereas chronic one exhibits a weaker response. Our study elucidated HBV-specific T cell responses in terms of viral abundance rather than the timing of infection. We showed that in the premalignant stage, the degree of impaired T cell function was not synchronized with the viral surface antigen, which was attributed the liver's tolerance to the virus. However, after the development of hepatocellular carcinoma, T cell exhaustion was inevitable, and it was marked by the exhaustion of the signature transcription factor TOX.
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Affiliation(s)
- Banglun Pan
- Department of Hepatobiliary Surgery, Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Zengbin Wang
- Department of Immunology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China
| | - Rui Chen
- Department of Hepatobiliary Surgery, Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Xiaoxia Zhang
- Department of Hepatobiliary Surgery, Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Jiacheng Qiu
- Department of Hepatobiliary Surgery, Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Xiaoxuan Wu
- Department of Hepatobiliary Surgery, Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Yuxin Yao
- Department of Hepatobiliary Surgery, Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Yue Luo
- Department of Hepatobiliary Surgery, Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Xiaoqian Wang
- Department of Hepatobiliary Surgery, Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Cancer Center of Fujian Medical University, Fujian Medical University Union Hospital, Fuzhou, China
| | - Nanhong Tang
- Department of Hepatobiliary Surgery, Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Cancer Center of Fujian Medical University, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
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Zhou Y, Yuan K, Yang Y, Shan X, Ji Z, Zhou D, Ouyang J, Wang Z, Zhang Q, Zhou J, Li Q. Predictive Factors of Treatment Outcomes After Percutaneous Radiofrequency Ablation of Hepatocellular Carcinoma in the Hepatocaval Confluence: A Propensity Score Matching Analysis. Acad Radiol 2023; 30 Suppl 1:S92-S103. [PMID: 37173236 DOI: 10.1016/j.acra.2023.03.043] [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: 03/09/2023] [Revised: 03/30/2023] [Accepted: 03/31/2023] [Indexed: 05/15/2023]
Abstract
RATIONALE AND OBJECTIVES To compare the efficacy and complications of ultrasound-guided percutaneous radiofrequency ablation of hepatocellular carcinoma (HCC) in the hepatocaval confluence with those of HCC in the non-hepatocaval confluence and to explore the risk factors that lead to radiofrequency ablation failure and patient local tumor progression (LTP). MATERIALS AND METHODS From January 2017 to January 2022, 86 patients with HCC in the hepatocaval confluence who had radiofrequency ablation were included. A 1:1 propensity-matched group of patients with HCC in the non-hepatocaval confluence with comparable clinical baseline traits, such as tumor diameter and tumor number, served as the control group. The two groups' complications, primary efficacy rate (PER), technical success rate (TSR), and prognosis were estimated. RESULTS After PSM, no significant difference of TSR (91.7% vs 95.8%, p = 0.491) and PER (95.8% vs 97.2%, p = 1.000) and 1-, 3-, and 5-year LTP rate (12.5% vs 9.9%, 28.2% vs 27.7%, 40.8% vs 43.8%, p = 0.959) and 1-, 3-, and 5-year DFS rate (87.5% vs 87.5%, 62.3% vs 54.2%, 18.1% vs 22.6%, p = 0.437) and 1-, 3-, and 5-year OS rate (94.3% vs 95.7%, 72.7% vs 69.6%, 20.9% vs 33.6%, p = 0.904) was detected between the two groups. The tumor-to-IVC distance was an independent risk factor for radiofrequency ablation failure in HCC patients in the hepatocaval confluence (OR = 0.611, p = 0.022). Besides, tumor diameter was an independent risk factor for predicting LTP in patients with HCC in the hepatocaval confluence (HR = 2.209, p = 0.046). CONCLUSION HCC in the hepatocaval confluence can be effectively treated with radiofrequency ablation. To maximize treatment efficacy, the tumor-to-IVC distance and tumor diameter should be assessed before the operation begins.
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Affiliation(s)
- Yanzhao Zhou
- Department of Hepatobiliary Cancer, Liver Cancer Research Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China (Y.Z., Q.Z., Q.L.)
| | - Kun Yuan
- School of Public Health, Capital Medical University, Beijing, China (K.Y.)
| | - Yi Yang
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China (Y.Y., X.S., Z.J., D.Z., J.O., Z.W., J.Z.)
| | - Xiao Shan
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China (Y.Y., X.S., Z.J., D.Z., J.O., Z.W., J.Z.)
| | - Zemin Ji
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China (Y.Y., X.S., Z.J., D.Z., J.O., Z.W., J.Z.)
| | - Dezheng Zhou
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China (Y.Y., X.S., Z.J., D.Z., J.O., Z.W., J.Z.)
| | - Jingzhong Ouyang
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China (Y.Y., X.S., Z.J., D.Z., J.O., Z.W., J.Z.)
| | - Zhengzheng Wang
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China (Y.Y., X.S., Z.J., D.Z., J.O., Z.W., J.Z.)
| | - Qi Zhang
- Department of Hepatobiliary Cancer, Liver Cancer Research Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China (Y.Z., Q.Z., Q.L.)
| | - Jinxue Zhou
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China (Y.Y., X.S., Z.J., D.Z., J.O., Z.W., J.Z.)
| | - Qiang Li
- Department of Hepatobiliary Cancer, Liver Cancer Research Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China (Y.Z., Q.Z., Q.L.).
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11
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Lu Y, Liang L, Lu WF, Cheng J, Yao WF, Xie YM, Wang DD, Xu FQ, Xiao ZQ, Zhang JG, Liu JW, Zhang CW, Huang DS. The prognosis of elderly patients with hepatocellular carcinoma after curative hepatectomy a multicenter competing risk analysis. Clin Res Hepatol Gastroenterol 2023; 47:102147. [PMID: 37245639 DOI: 10.1016/j.clinre.2023.102147] [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: 04/01/2023] [Revised: 05/25/2023] [Accepted: 05/25/2023] [Indexed: 05/30/2023]
Abstract
BACKGROUND Non-cancer-specific death (NCSD) is an important factor that needs to be considered in patients with malignancy, as it can affect their long-term prognosis. In particular, the effect of age on patients with hepatocellular carcinoma (HCC) after hepatectomy requires clarification. This study aims to examine the impact of age on patients with HCC after hepatectomy and to identify independent risk factors of survival. METHODS Patients with HCC that fell within the Milan Criteria and had undergone curative hepatectomy were included in this study. The patients were divided into two groups: young patients (age <70) and elderly patients (age ≥70). Perioperative complications, cancer-specific death (CSD), recurrence, and NCSD were all recorded and analyzed. Multivariate analyses were performed to identify independent risk factors of survival using Fine and Gray's competing-risk regression model. RESULTS Among 1,354 analytic patients, 1,068 (78.7%) were stratified into the young group and 286 (21.3%) into the elderly group. The elderly group had a higher 5-year cumulative incidence of NCSD (12.6% vs. 3.7% for the young group, P < 0.001), but lower 5-year cumulative incidences of recurrence (20.3% vs. 21.1% for the young group, P = 0.041) and CSD (14.3% vs. 15.5% for the young group, P = 0.066). Multivariate competing-risk regression analyses revealed that age was independently associated with NCSD (subdistribution hazard ratio (SHR) 3.003, 95%CI: 2.082-4.330, P < 0.001), but not with recurrence (SHR 0.837, 95%CI: 0.659-1.060, P = 0.120) or CSD (SHR 0.736, 95%CI: 0.537-1.020, P = 0.158). CONCLUSION For patients with early-stage HCC after hepatectomy, older age was independently associated with NCSD, but not recurrence and CSD.
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Affiliation(s)
- Yi Lu
- Department of Clinical Medicine, Medical College of Soochow University, Suzhou, China; General Surgery, Cancer Center, Department of Hepatobiliary and Pancreatic Surgery and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China
| | - Lei Liang
- General Surgery, Cancer Center, Department of Hepatobiliary and Pancreatic Surgery and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China.
| | - Wen Feng Lu
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
| | - Jian Cheng
- General Surgery, Cancer Center, Department of Hepatobiliary and Pancreatic Surgery and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China
| | - Wei Feng Yao
- General Surgery, Cancer Center, Department of Hepatobiliary and Pancreatic Surgery and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China
| | - Ya Ming Xie
- General Surgery, Cancer Center, Department of Hepatobiliary and Pancreatic Surgery and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China
| | - Dong Dong Wang
- General Surgery, Cancer Center, Department of Hepatobiliary and Pancreatic Surgery and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China
| | - Fei Qi Xu
- General Surgery, Cancer Center, Department of Hepatobiliary and Pancreatic Surgery and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China
| | - Zun Qiang Xiao
- General Surgery, Cancer Center, Department of Hepatobiliary and Pancreatic Surgery and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China
| | - Jun Gang Zhang
- General Surgery, Cancer Center, Department of Hepatobiliary and Pancreatic Surgery and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China
| | - Jun Wei Liu
- General Surgery, Cancer Center, Department of Hepatobiliary and Pancreatic Surgery and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China
| | - Cheng Wu Zhang
- General Surgery, Cancer Center, Department of Hepatobiliary and Pancreatic Surgery and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China
| | - Dong Sheng Huang
- Department of Clinical Medicine, Medical College of Soochow University, Suzhou, China; General Surgery, Cancer Center, Department of Hepatobiliary and Pancreatic Surgery and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China; Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang, China.
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12
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Wicks JS, Dale BS, Ruffolo L, Pack LJ, Dunne R, Laryea MA, Hernandez-Alejandro R, Sharma AK. Comparable and Complimentary Modalities for Treatment of Small-Sized HCC: Surgical Resection, Radiofrequency Ablation, and Microwave Ablation. J Clin Med 2023; 12:5006. [PMID: 37568408 PMCID: PMC10419984 DOI: 10.3390/jcm12155006] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Revised: 07/20/2023] [Accepted: 07/28/2023] [Indexed: 08/13/2023] Open
Abstract
BACKGROUND Over the past decade, there has been continual improvement in both ablative and surgical technologies for the treatment of hepatocellular carcinoma (HCC). The efficacy of ablative therapy compared to surgical resection for HCC has not been thoroughly evaluated using multiple large-scale randomized controlled trials. By international consensus, if a patient is eligible, surgery is the primary curative treatment option, as it is believed to confer superior oncologic control. OBJECTIVE to determine the efficacies of percutaneous ablative therapies and surgical resection (SR) in the treatment of HCC. Data sources, study appraisal, and synthesis methods: A meta-analysis using 5 online databases dating back to 1989 with more than 31,000 patients analyzing patient and tumor characteristics, median follow-up, overall survival, and complication rate was performed. RESULTS Ablative therapies are suitable alternatives to surgical resection in terms of survival and complication rates for comparable patient populations. For the entire length of the study from 1989-2019, radiofrequency ablation (RFA) produced the highest 5-year survival rates (59.6%), followed by microwave ablation (MWA) (50.7%) and surgical resection (SR) (49.9%). In the most recent era from 2006 to 2019, surgical resection has produced the highest 5-year survival rate of 72.8%, followed by RFA at 61.7% and MWA at 50.6%. Conclusions and key findings: Depending on the disease state and comorbidities of the patient, one modality may offer superior overall survival rates over the other available techniques. Interventional ablative methods and surgical resection should be used in conjunction for the successful treatment of small-sized HCC.
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Affiliation(s)
- Jeffrey S. Wicks
- Department of Biology, University of Rochester, Rochester, NY 14642, USA;
| | - Benjamin S. Dale
- Department of Surgery, University of Rochester, Rochester, NY 14642, USA; (B.S.D.); (L.R.)
| | - Luis Ruffolo
- Department of Surgery, University of Rochester, Rochester, NY 14642, USA; (B.S.D.); (L.R.)
| | - Ludia J. Pack
- Department of Genetics, University of Rochester, Rochester, NY 14642, USA;
| | - Richard Dunne
- Division of Hematology/Oncology, Department of Medicine, University of Rochester, Rochester, NY 14642, USA;
| | - Marie A. Laryea
- Division of Gastroenterology/Hepatology, Department of Medicine, University of Rochester, Rochester, NY 14642, USA;
| | | | - Ashwani Kumar Sharma
- Division of Interventional Radiology, Department of Imaging Sciences, University of Rochester, Rochester, NY 14642, USA
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13
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Peri V, Lee E, Fink M, Starkey G, Nikfarjam M, Yoshino O, Furtado R, Sinclair M, Testro A, Majumdar A, Jones R, Muralidharan V, Perini MV. A Single Centre Experience with Pre-Operative Markers in the Prediction of Outcomes after Liver Resection for Hepatocellular Carcinoma. J Gastrointest Surg 2023; 27:1376-1386. [PMID: 37095335 DOI: 10.1007/s11605-023-05681-1] [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: 12/16/2022] [Accepted: 04/08/2023] [Indexed: 04/26/2023]
Abstract
BACKGROUND AND AIM The C-reactive protein to albumin ratio, albumin-bilirubin index and platelet-albumin-bilirubin index have emerged as prognostic scores in hepatocellular carcinoma, although their clinical utility remains unclear, with ongoing investigation in multiple patient populations. This study aims to report survival outcomes and evaluate these indices in a cohort of patients undergoing liver resection for hepatocellular carcinoma in a tertiary Australian centre. METHODS This retrospective study reviewed data from the Department of Surgery at Austin Health and electronic health records (Cerner corporation). The impact of pre, intra and post-operative parameters on post-operative complications, overall and recurrence free survival were analyzed. RESULTS 163 liver resections were performed in 157 patients between 2007 and 2020. Post-operative complications occurred in 58 patients (35.6%), with pre-operative albumin < 36.5 g/L (3.41(1.41-8.29),p = 0.007) and open liver resection (3.93(1.38-11.21),p = 0.011) demonstrating independent predictive significance. 1,3 and 5-year overall survival was 91.0%, 76.7% and 66.9% respectively, with a median survival time of 92.7 months (81.3-103.9). Hepatocellular carcinoma recurred in 95 patients (58.3%) with a median time to recurrence of 27.8 months (15.6-39.9). 1,3 and 5 year recurrence-free survival rates were 94.0%, 73.7% and 55.1% respectively. Pre-operative C-reactive protein-albumin ratio > 0.034 was significantly associated with reduced overall (4.39(1.19-16.16),p = 0.026) and recurrence-free (2.53(1.21-5.30),p = 0.014) survival. CONCLUSION C-reactive protein-albumin ratio > 0.034 is a strong predictor of poor prognosis following liver resection for hepatocellular carcinoma. In addition, pre-operative hypoalbuminemia was associated with post-operative complications, and future studies are required to assess the potential benefits of albumin replacement in reducing post-surgical morbidity.
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Affiliation(s)
- Varun Peri
- Department of Surgery (Austin Precinct), LVL 8, LTB, Austin Hospital, The University of Melbourne, 145 Studley Road, Heidelberg, 3084, Australia
| | - Eunice Lee
- Department of Surgery (Austin Precinct), LVL 8, LTB, Austin Hospital, The University of Melbourne, 145 Studley Road, Heidelberg, 3084, Australia
- HPB & Liver Transplant Unit, 145 Studley Road, Austin HealthHeidelberg, 3084, Australia
| | - Michael Fink
- Department of Surgery (Austin Precinct), LVL 8, LTB, Austin Hospital, The University of Melbourne, 145 Studley Road, Heidelberg, 3084, Australia
- HPB & Liver Transplant Unit, 145 Studley Road, Austin HealthHeidelberg, 3084, Australia
| | - Graham Starkey
- HPB & Liver Transplant Unit, 145 Studley Road, Austin HealthHeidelberg, 3084, Australia
| | - Mehrdad Nikfarjam
- Department of Surgery (Austin Precinct), LVL 8, LTB, Austin Hospital, The University of Melbourne, 145 Studley Road, Heidelberg, 3084, Australia
- HPB & Liver Transplant Unit, 145 Studley Road, Austin HealthHeidelberg, 3084, Australia
| | - Osamu Yoshino
- HPB & Liver Transplant Unit, 145 Studley Road, Austin HealthHeidelberg, 3084, Australia
| | - Ruelan Furtado
- HPB & Liver Transplant Unit, 145 Studley Road, Austin HealthHeidelberg, 3084, Australia
| | - Marie Sinclair
- Victorian Liver Transplant Unit, 145 Studley Road, Austin HealthHeidelberg, 3084, Australia
| | - Adam Testro
- Victorian Liver Transplant Unit, 145 Studley Road, Austin HealthHeidelberg, 3084, Australia
| | - Avik Majumdar
- Victorian Liver Transplant Unit, 145 Studley Road, Austin HealthHeidelberg, 3084, Australia
| | - Robert Jones
- Department of Surgery (Austin Precinct), LVL 8, LTB, Austin Hospital, The University of Melbourne, 145 Studley Road, Heidelberg, 3084, Australia
- HPB & Liver Transplant Unit, 145 Studley Road, Austin HealthHeidelberg, 3084, Australia
| | - Vijayaragavan Muralidharan
- Department of Surgery (Austin Precinct), LVL 8, LTB, Austin Hospital, The University of Melbourne, 145 Studley Road, Heidelberg, 3084, Australia
- HPB & Liver Transplant Unit, 145 Studley Road, Austin HealthHeidelberg, 3084, Australia
| | - Marcos Vinicius Perini
- Department of Surgery (Austin Precinct), LVL 8, LTB, Austin Hospital, The University of Melbourne, 145 Studley Road, Heidelberg, 3084, Australia.
- HPB & Liver Transplant Unit, 145 Studley Road, Austin HealthHeidelberg, 3084, Australia.
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Deng M, Lei Q, Wang J, Lee C, Guan R, Li S, Wei W, Chen H, Zhong C, Guo R. Nomograms for predicting the recurrence probability and recurrence-free survival in patients with hepatocellular carcinoma after conversion hepatectomy based on hepatic arterial infusion chemotherapy: a multicenter, retrospective study. Int J Surg 2023; 109:1299-1310. [PMID: 37038994 PMCID: PMC10389618 DOI: 10.1097/js9.0000000000000376] [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: 12/04/2022] [Accepted: 03/24/2023] [Indexed: 04/12/2023]
Abstract
BACKGROUND This study aimed to establish and validate nomograms to predict the probability of recurrence and recurrence-free survival (RFS) in patients with hepatocellular carcinoma (HCC) after conversion hepatectomy based on hepatic arterial infusion chemotherapy (HAIC). METHODS Nomograms were constructed using data from a retrospective study of 214 consecutive patients treated with HAIC-based conversion liver resection between January 2016 and July 2020. Nomograms predicting the probability of tumor recurrence and RFS were established based on predictors selected by multivariate regression analysis. Predictive accuracy and discriminative ability of the nomogram were examined. Bootstrap method was used for internal validation. External validation was performed using cohorts ( n =128) from three other centers. RESULTS Recurrence rates in the primary and external validation cohorts were 63.6 and 45.3%, respectively. Nomograms incorporating clinicopathological features of tumor recurrence and RFS were generated. Concordance index (C-index) scores of the nomograms for predicting recurrence probability and RFS were 0.822 (95% CI, 0.703-0.858) and 0.769 (95% CI, 0.731-0.814) in the primary cohort, and 0.802 (95% CI, 0.726-0.878) and 0.777 (95% CI, 0.719-0.835) in the external validation cohort, respectively. Calibration curves indicated good agreement between the nomograms and actual observations. Moreover, the nomograms outperformed the commonly used staging systems. Patients with low risk, stratified by the median nomogram scores had better RFS (low risk vs. high risk, 36.5 vs. 5.2 months, P <0.001). The external validation cohort supported these findings. CONCLUSIONS The presented nomograms showed favorable accuracy for predicting recurrence probability and RFS in HCC patients treated with HAIC-based conversion hepatectomy. Identifying risk factors and estimating tumor recurrence may help clinicians in the decision-making process regarding adjuvant therapies for patients with HCC, which eventually achieves better oncological outcomes.
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Affiliation(s)
- Min Deng
- Department of Liver Surgery, Sun Yat-sen University Cancer Center
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine
| | - Qiucheng Lei
- Department of Hepatic Surgery, The Affiliated Foshan Hospital of Sun Yat-Sen University, Foshan, China
| | - Jiamin Wang
- Department of Gastroenterology, University of Chinese Academy of Sciences Shenzhen Hospital, Shenzhen
| | - Carol Lee
- Department of Surgery, The Chinese University of Hong Kong, Hong Kong Special Administrative Region
| | - Renguo Guan
- Department of Liver Surgery, Sun Yat-sen University Cancer Center
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine
| | - Shaohua Li
- Department of Liver Surgery, Sun Yat-sen University Cancer Center
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine
| | - Wei Wei
- Department of Liver Surgery, Sun Yat-sen University Cancer Center
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine
| | - Huanwei Chen
- Department of Hepatic Surgery, The Affiliated Foshan Hospital of Sun Yat-Sen University, Foshan, China
| | - Chong Zhong
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou
| | - Rongping Guo
- Department of Liver Surgery, Sun Yat-sen University Cancer Center
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine
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15
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Korean Liver Cancer Association (KLCA) and National Cancer Center (NCC) Korea. 2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma. JOURNAL OF LIVER CANCER 2023; 23:1-120. [PMID: 37384024 PMCID: PMC10202234 DOI: 10.17998/jlc.2022.11.07] [Citation(s) in RCA: 68] [Impact Index Per Article: 34.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/05/2022] [Accepted: 11/07/2022] [Indexed: 06/30/2023]
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the fourth most common cancer among men in South Korea, where the prevalence of chronic hepatitis B infection is high in middle and old age. The current practice guidelines will provide useful and sensible advice for the clinical management of patients with HCC. A total of 49 experts in the fields of hepatology, oncology, surgery, radiology, and radiation oncology from the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2018 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions. These guidelines provide useful information and direction for all clinicians, trainees, and researchers in the diagnosis and treatment of HCC.
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Affiliation(s)
- Korean Liver Cancer Association (KLCA) and National Cancer Center (NCC) Korea
- Corresponding author: KLCA-NCC Korea Practice Guideline Revision Committee (KPGRC) (Committee Chair: Joong-Won Park) Center for Liver and Pancreatobiliary Cancer, Division of Gastroenterology, Department of Internal Medicine, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang 10408, Korea Tel. +82-31-920-1605, Fax: +82-31-920-1520, E-mail:
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16
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Yang C, Wang H, Liu J, Yang F, Lv L, Jiang Y, Cai Q. Pre- to postoperative alpha-fetoprotein ratio-based nomogram to predict tumor recurrence in patients with hepatocellular carcinoma. Front Oncol 2023; 13:1134933. [PMID: 37124520 PMCID: PMC10140353 DOI: 10.3389/fonc.2023.1134933] [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: 12/31/2022] [Accepted: 03/20/2023] [Indexed: 05/02/2023] Open
Abstract
Background This study aimed to investigate the role of the alpha fetoprotein (AFP) ratio before and after curative resection in the prognosis of patients with hepatocellular carcinoma (HCC) and to develop a novel pre- to postoperative AFP ratio nomogram to predict recurrence free survival (RFS) for HCC patients after curative resection. Methods A total of 485 pathologically confirmed HCC patients who underwent radical hepatectomy from January 2010 to December 2018 were retrospectively analyzed. The independent prognostic factors of hepatocellular carcinoma were identified by multivariate COX proportional model analysis, and the nomogram model was constructed. The receiver operating characteristic and the C-index were used to evaluate the accuracy and efficacy of the model prediction, the correction curve was used to assess the calibration of the prediction model, and decision curve analysis was used to evaluate the clinical application value of the nomogram model. Results A total of 485 HCC patients were divided into the training cohort (n = 340) and the validation cohort (n = 145) by random sampling at a ratio of 7:3. Using X-tile software, it was found that the optimal cut-off value of the AFP ratio in the training cohort was 0.8. In both cohorts, the relapse-free survival of patients with an AFP ratio <0.8 (high-risk group) was significantly shorter than in those with an AFP ratio ≥0.8 (low-risk group) (P < 0.05). An AFP ratio <0.8 was an independent risk factor for recurrence of HCC after curative resection. Based on the AFP ratio, BCLC stage and cirrhosis diagnosis, a satisfactory nomogram was developed. The AUC of our nomogram for predicting 1-, 3-, and 5-year RFS was 0.719, 0.690, and 0.708 in the training cohort and 0.721, 0.682, and 0.681 in the validation cohort, respectively. Furthermore, our model demonstrated excellent stratification as well as clinical applicability. Conclusion The AFP ratio was a reliable biomarker for tumor recurrence. This easy-to-use AFP ratio-based nomogram precisely predicted tumor recurrence in HCC patients after curative resection.
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Affiliation(s)
- Chengkai Yang
- The Fuzong Clinical Medical College of Fujian Medical University, Fuzhou, China
| | - Huaxiang Wang
- The Fuzong Clinical Medical College of Fujian Medical University, Fuzhou, China
- Department of Hepatobiliary and Pancreatic Surgery, Taihe Hospital, Affiliated Hospital of Hubei University of Medicine, Shiyan, China
| | - Jianyong Liu
- Department of Hepatobiliary Surgery, 900 Hospital of The Joint Logistics Team, Fuzhou, China
| | - Fang Yang
- Department of Hepatobiliary Surgery, 900 Hospital of The Joint Logistics Team, Fuzhou, China
| | - Lizhi Lv
- Department of Hepatobiliary Surgery, 900 Hospital of The Joint Logistics Team, Fuzhou, China
| | - Yi Jiang
- Department of Hepatobiliary Surgery, 900 Hospital of The Joint Logistics Team, Fuzhou, China
- *Correspondence: Qiucheng Cai, ; Yi Jiang,
| | - Qiucheng Cai
- Department of Hepatobiliary Surgery, 900 Hospital of The Joint Logistics Team, Fuzhou, China
- *Correspondence: Qiucheng Cai, ; Yi Jiang,
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Wu F, Chen B, Dong D, Rong W, Wang H, Wang L, Wang S, Jin J, Song Y, Liu Y, Fang H, Tang Y, Li N, Zhu X, Li Y, Wang W, Wu J. Phase 2 Evaluation of Neoadjuvant Intensity-Modulated Radiotherapy in Centrally Located Hepatocellular Carcinoma: A Nonrandomized Controlled Trial. JAMA Surg 2022; 157:1089-1096. [PMID: 36197682 PMCID: PMC9535533 DOI: 10.1001/jamasurg.2022.4702] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2022] [Accepted: 07/16/2022] [Indexed: 01/11/2023]
Abstract
Importance Centrally located hepatocellular carcinoma (HCC) is a special type of HCC whose outcome is unsatisfactory when treated with surgery alone. No standard adjuvant or neoadjuvant treatment for this disease has been established that improves clinical outcomes. Objective To evaluate the effectiveness and safety of adding neoadjuvant intensity-modulated radiotherapy (IMRT) before surgery in patients with centrally located HCC. Design, Setting, and Participants This phase 2, single-center, single-group prospective nonrandomized controlled trial was conducted between December 16, 2014, and January 29, 2019, at the Cancer Institute and Hospital of the Chinese Academy of Medical Sciences in Beijing, China. The last follow-up was on July 30, 2021. Patients with centrally located HCC who underwent neoadjuvant IMRT and surgery were included in the analysis. Interventions Neoadjuvant IMRT followed by hepatectomy. Main Outcomes and Measures The primary end point was 5-year overall survival (OS). The secondary end points were tumor response to IMRT, 5-year disease-free survival (DFS), and treatment-related adverse events. Results Thirty-eight patients (mean [SD] age, 55.6 [9.3] years; 35 male [92.1%] individuals) completed the prescribed neoadjuvant IMRT without interruption. Radiographic tumor response to IMRT before surgery included partial response (16 [42.1%]) and stable disease (22 [57.9%]). Thirteen patients (34.2%) achieved major pathological response, of which 5 (13.2%) achieved pathologic complete response. With a median follow-up of 45.8 months, the median OS was not reached, and the OS rates were 94.6% at 1 year, 75.4% at 3 years, and 69.1% at 5 years. The median DFS was 45.8 months, and DFS rates were 70.3% at 1 year, 54.1% at 3 years, and 41.0% at 5 years. Radiotherapy-related grade 3 adverse events were observed in 3 patients (7.9%). Nineteen operative complications developed in 13 patients (34.2%), including grade I to II complications in 12 patients (31.6%) and grade IIIa complication in 1 patient (2.6%). No grade IIIb or higher operative complications were observed. Conclusions and Relevance Results of this trial suggest that neoadjuvant IMRT plus surgery is effective and well-tolerated in patients with centrally located HCC. These data may inform a future randomized clinical trial of this new treatment strategy. Trial Registration ClinicalTrials.gov Identifier: NCT02580929.
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Affiliation(s)
- Fan Wu
- Department of Hepatobiliary Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Bo Chen
- Department of Radiation Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Dezuo Dong
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Weiqi Rong
- Department of Hepatobiliary Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hongzhi Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Liming Wang
- Department of Hepatobiliary Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Shulian Wang
- Department of Radiation Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jing Jin
- Department of Radiation Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yongwen Song
- Department of Radiation Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yueping Liu
- Department of Radiation Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hui Fang
- Department of Radiation Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yuan Tang
- Department of Radiation Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ning Li
- Department of Radiation Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xianggao Zhu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Yexiong Li
- Department of Radiation Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Weihu Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Jianxiong Wu
- Department of Hepatobiliary Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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18
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2022 KLCA-NCC Korea Practice Guidelines for the Management of Hepatocellular Carcinoma. Korean J Radiol 2022; 23:1126-1240. [PMID: 36447411 PMCID: PMC9747269 DOI: 10.3348/kjr.2022.0822] [Citation(s) in RCA: 80] [Impact Index Per Article: 26.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Accepted: 10/28/2022] [Indexed: 11/18/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the fourth most common cancer among men in South Korea, where the prevalence of chronic hepatitis B infection is high in middle and old age. The current practice guidelines will provide useful and sensible advice for the clinical management of patients with HCC. A total of 49 experts in the fields of hepatology, oncology, surgery, radiology, and radiation oncology from the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2018 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions. These guidelines provide useful information and direction for all clinicians, trainees, and researchers in the diagnosis and treatment of HCC.
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19
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Ruffolo LI, Zambrano D, Dale BS, Nimmagadda SV, Hack M, Gaba H, Belt BA, Burchard PR, LanzDuret-Hernandez JM, Dokus MK, Aponte JP, Tomiyama K, Nair A, Pineda-Solis K, Hernandez-Alejandro R. Inferior Survival Is Associated With Socioeconomic Deprivation in Hepatocellular Carcinoma. J Surg Res 2022; 279:228-239. [DOI: 10.1016/j.jss.2022.05.035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Revised: 04/14/2022] [Accepted: 05/06/2022] [Indexed: 10/31/2022]
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20
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2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma. Clin Mol Hepatol 2022; 28:583-705. [PMID: 36263666 PMCID: PMC9597235 DOI: 10.3350/cmh.2022.0294] [Citation(s) in RCA: 174] [Impact Index Per Article: 58.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Accepted: 09/23/2022] [Indexed: 01/27/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the fourth most common cancer among men in South Korea, where the prevalence of chronic hepatitis B infection is high in middle and old age. The current practice guidelines will provide useful and sensible advice for the clinical management of patients with HCC. A total of 49 experts in the fields of hepatology, oncology, surgery, radiology, and radiation oncology from the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2018 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions. These guidelines provide useful information and direction for all clinicians, trainees, and researchers in the diagnosis and treatment of HCC.
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21
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Yang D, Zhu M, Xiong X, Su Y, Zhao F, Hu Y, Zhang G, Pei J, Ding Y. Clinical features and prognostic factors in patients with microvascular infiltration of hepatocellular carcinoma: Development and validation of a nomogram and risk stratification based on the SEER database. Front Oncol 2022; 12:987603. [PMID: 36185206 PMCID: PMC9515492 DOI: 10.3389/fonc.2022.987603] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2022] [Accepted: 08/29/2022] [Indexed: 11/29/2022] Open
Abstract
Background The goal is to establish and validate an innovative prognostic risk stratification and nomogram in patients of hepatocellular carcinoma (HCC) with microvascular invasion (MVI) for predicting the cancer-specific survival (CSS). Methods 1487 qualified patients were selected from the Surveillance, Epidemiology and End Results (SEER) database and randomly assigned to the training cohort and validation cohort in a ratio of 7:3. Concordance index (C-index), area under curve (AUC) and calibration plots were adopted to evaluate the discrimination and calibration of the nomogram. Decision curve analysis (DCA) was used to quantify the net benefit of the nomogram at different threshold probabilities and compare it to the American Joint Committee on Cancer (AJCC) tumor staging system. C-index, net reclassification index (NRI) and integrated discrimination improvement (IDI) were applied to evaluate the improvement of the new model over the AJCC tumor staging system. The new risk stratifications based on the nomogram and the AJCC tumor staging system were compared. Results Eight prognostic factors were used to construct the nomogram for HCC patients with MVI. The C-index for the training and validation cohorts was 0.785 and 0.776 respectively. The AUC values were higher than 0.7 both in the training cohort and validation cohort. The calibration plots showed good consistency between the actual observation and the nomogram prediction. The IDI values of 1-, 3-, 5-year CSS in the training cohort were 0.17, 0.16, 0.15, and in the validation cohort were 0.17, 0.17, 0.17 (P<0.05). The NRI values of the training cohort were 0.75 at 1-year, 0.68 at 3-year and 0.67 at 5-year. The DCA curves indicated that the new model more accurately predicted 1-year, 3-year, and 5-year CSS in both training and validation cohort, because it added more net benefit than the AJCC staging system. Furthermore, the risk stratification system showed the CSS in different groups had a good regional division. Conclusions A comprehensive risk stratification system and nomogram were established to forecast CSS for patients of HCC with MVI.
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Affiliation(s)
- Dashuai Yang
- Department of Hepatobiliary Surgery, Renmin Hospital of Wuhan University, Wuhan, China
| | - Mingqiang Zhu
- Department of Hepatobiliary Surgery, Renmin Hospital of Wuhan University, Wuhan, China
| | - Xiangyun Xiong
- Department of Hepatobiliary Surgery, Renmin Hospital of Wuhan University, Wuhan, China
| | - Yang Su
- Department of Gastrointestinal Surgery, Tongji Hospital, Tongji Medical College in Huazhong University of Science and Technology, Wuhan, China
| | - Fangrui Zhao
- Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Yong Hu
- Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, China
- *Correspondence: Youming Ding, ; Yong Hu,
| | - Guo Zhang
- Department of neurosurgery, Renmin Hospital of Wuhan University, Wuhan, China
| | - Junpeng Pei
- Department of Hepatobiliary Surgery, Renmin Hospital of Wuhan University, Wuhan, China
| | - Youming Ding
- Department of Hepatobiliary Surgery, Renmin Hospital of Wuhan University, Wuhan, China
- *Correspondence: Youming Ding, ; Yong Hu,
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22
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Zhang Y, Lei X, Xu L, Lv X, Xu M, Tang H. Preoperative and postoperative nomograms for predicting early recurrence of hepatocellular carcinoma without macrovascular invasion after curative resection. BMC Surg 2022; 22:233. [PMID: 35715787 PMCID: PMC9205542 DOI: 10.1186/s12893-022-01682-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Accepted: 06/06/2022] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Postoperative early recurrence (ER) is a major obstacle to long-term survival after curative liver resection (LR) in patients with hepatocellular carcinoma (HCC). This study aimed to establish preoperative and postoperative nomograms to predict ER in HCC without macrovascular invasion. METHODS Patients who underwent curative LR for HCC between January 2012 and December 2016 were divided into training and internal prospective validation cohorts. Nomograms were constructed based on independent risk factors derived from the multivariate logistic regression analyses in the training cohort. The predictive performances of the nomograms were validated using the internal prospective validation cohort. RESULTS In total, 698 patients fulfilled the eligibility criteria. Among them, 265 of 482 patients (55.0%) in the training cohort and 120 of 216 (55.6%) patients in the validation cohort developed ER. The preoperative risk factors associated with ER were age, alpha-fetoprotein, tumor diameter, and tumor number, and the postoperative risk factors associated with ER were age, tumor diameter, tumor number, microvascular invasion, and differentiation. The pre- and postoperative nomograms based on these factors showed good accuracy, with concordance indices of 0.712 and 0.850 in the training cohort, respectively, and 0.754 and 0.857 in the validation cohort, respectively. The calibration curves showed optimal agreement between the predictions by the nomograms and actual observations. The area under the receiver operating characteristic curves of the pre- and postoperative nomograms were 0.721 and 0.848 in the training cohort, respectively, and 0.754 and 0.844 in the validation cohort, respectively. CONCLUSIONS The nomograms constructed in this study showed good performance in predicting ER for HCC without macrovascular invasion before and after surgery. These nomograms would be helpful for doctors when determining treatments and selecting patients for regular surveillance or administration of adjuvant therapies.
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Affiliation(s)
- Yanfang Zhang
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Xuezhong Lei
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Liangliang Xu
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, China
| | - Xiaoju Lv
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Mingqing Xu
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, China.
| | - Hong Tang
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China.
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23
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Cao P, Hong H, Yu Z, Chen G, Qi S. A Novel Clinically Prognostic Stratification Based on Prognostic Nutritional Index Status and Histological Grade in Patients With Gallbladder Cancer After Radical Surgery. Front Nutr 2022; 9:850971. [PMID: 35600830 PMCID: PMC9116425 DOI: 10.3389/fnut.2022.850971] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2022] [Accepted: 04/05/2022] [Indexed: 11/13/2022] Open
Abstract
Purpose Gallbladder carcinoma (GBC) is the most common malignancy of the biliary tract, with a 5-year survival rate of 5%. The prognostic models to predict the prognosis of patients with GBC remain controversial. Therefore, to construct a prognosis prediction of GBC, a retrospective cohort study was carried out to investigate the prognostic nutritional index and histological grade in the long-term outcome of patients with GBC after radical surgery (RS). Methods A retrospective study of a total of 198 patients with GBC who underwent surgical treatment were enrolled. The hematological indicators, imageological data, and perioperative clinical data were acquired for statistical analysis and poor prognosis model construction. Results Prognostic nutrition index (PNI) < 45.88, maximum tumor diameter (MTD) > 2.24 cm, and jaundice (JD) were all associated with a poor prognosis in multivariate logistic regression analysis. The prognosis prediction model was based on the three risk factors, which indicated a superior predictive ability in the primary cohort [area under the curve (AUC) = 0.951] and validation cohort (AUC = 0.888). In multivariate Cox regression analysis, poorly differentiation (PD) was associated with poor 3-year survival. In addition, Kaplan-Meier (KM) survival analysis suggested that GBC patients with high-risk scores and PD had a better prognosis after RS (p < 0.05), but there was no significant difference in prognosis for patients with non-poorly differentiation (NPD) or low-risk scores after RS (p > 0.05). Conclusion Our prediction model for GBC patients with prognosis evaluation is accurate and effective. For patients with PD and high-risk scores, RS is highly recommended; a simple cholecystectomy can also be considered for acceptance for patients with NPD or low-risk score. The significant findings provide a new therapeutic strategy for the clinical treatment of GBC.
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Affiliation(s)
- Peng Cao
- Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China
- Department of Hepatobiliary Surgery and Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital, Fujian Medical University Cancer Center, Fuzhou, China
| | - Haijie Hong
- Department of Hepatobiliary Surgery and Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital, Fujian Medical University Cancer Center, Fuzhou, China
| | - Zijian Yu
- Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China
| | - Guodong Chen
- Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China
| | - Shuo Qi
- Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China
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24
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Zhang XF, Xue F, Bagante F, Ratti F, Marques HP, Silva S, Soubrane O, Lam V, Poultsides GA, Popescu I, Grigorie R, Alexandrescu S, Martel G, Workneh A, Guglielmi A, Hugh T, Aldrighetti L, Lv Y, Pawlik TM. Non-transplantable Recurrence After Resection for Transplantable Hepatocellular Carcinoma: Implication for Upfront Treatment Choice. J Gastrointest Surg 2022; 26:1021-1029. [PMID: 34797558 DOI: 10.1007/s11605-021-05206-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Accepted: 11/13/2021] [Indexed: 01/31/2023]
Abstract
OBJECTIVES To identify the preoperative risk factors for prediction of non-transplantable recurrence (NTR) after tumor resection for early-stage hepatocellular carcinoma (HCC) to assist in patient selection relative to upfront liver resection (LR) versus liver transplantation (LT). METHODS Patients who underwent curative resection for transplantable HCC and chronic liver disease were identified from an international multi-institutional database. NTR was defined as recurrence beyond the Milan or UCSF criteria, and the preoperative risk factors of NTR were investigated. RESULTS Among 293 patients with transplantable HCC within Milan criteria and 320 within UCSF criteria, 113 (38.6%) and 131 (40.9%) patients developed tumor recurrence, respectively. Among patients who recurred, NTR was present in 32 (28.3%) patients within Milan and 35 (26.7%) within UCSF criteria. When either Milan or UCSF criteria was adopted, three preoperative risk factors including liver cirrhosis, tumor size > 3 cm, and multiple lesions were consistently identified as risk factors associated with NTR after curative resection. By summing up the three factors, a scoring model was established and the incidence of NTR among patients with 0, 1 or ≥ 2 risk factors incrementally increased from 4.5%, 13.3% to 20.5% when Milan criteria was used, and from 4.5%, 12.4% to 33.9% when UCSF criteria was adopted. The model demonstrated very good discriminatory power on internal validation (n = 5,000) (c-index 0.689 for Milan criteria, and 0.715 for UCSF criteria). CONCLUSIONS Whereas surgical resection may be optimal first-line treatment for patients with no or one risk factor, patients with ≥ 2 risk factors should be considered for upfront liver transplantation.
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Affiliation(s)
- Xu-Feng Zhang
- Department of Hepatobiliary Surgery and Institute of Advanced Surgical Technology and Engineering, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.,Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, 395 W. 12th Ave., Suite 670, Columbus, OH, USA
| | - Feng Xue
- Department of Hepatobiliary Surgery and Institute of Advanced Surgical Technology and Engineering, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Fabio Bagante
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, 395 W. 12th Ave., Suite 670, Columbus, OH, USA.,Department of Surgery, University of Verona, Verona, Italy
| | | | - Hugo P Marques
- Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal
| | - Silvia Silva
- Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal
| | - Olivier Soubrane
- Department of Hepatobiliopancreatic Surgery, APHP, Beaujon Hospital, Clichy, France
| | - Vincent Lam
- Department of Surgery, Westmead Hospital, Sydney, Australia
| | | | - Irinel Popescu
- Department of Surgery, Fundeni Clinical Institute, Bucharest, Romania
| | - Razvan Grigorie
- Department of Surgery, Fundeni Clinical Institute, Bucharest, Romania
| | | | | | - Aklile Workneh
- Department of Surgery, University of Ottawa, Ottawa, Canada
| | | | - Tom Hugh
- Department of Surgery, School of Medicine, The University of Sydney, Sydney, Australia
| | | | - Yi Lv
- Department of Hepatobiliary Surgery and Institute of Advanced Surgical Technology and Engineering, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Timothy M Pawlik
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, 395 W. 12th Ave., Suite 670, Columbus, OH, USA.
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Preoperative application of systemic inflammatory biomarkers combined with MR imaging features in predicting microvascular invasion of hepatocellular carcinoma. Abdom Radiol (NY) 2022; 47:1806-1816. [PMID: 35267069 DOI: 10.1007/s00261-022-03473-w] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Revised: 02/21/2022] [Accepted: 02/21/2022] [Indexed: 02/07/2023]
Abstract
PURPOSE To investigate whether systemic inflammatory biomarkers compared with the imaging features interpreted by radiologists can offer complementary value for predicting the risk of microvascular invasion (MVI) in patients with hepatocellular carcinoma (HCC). METHODS A total of 156 patients with histologically confirmed HCC between Jan 2018 and Dec 2020 were retrospectively enrolled in the primary cohort. Preoperative clinical-inflammatory biomarkers and MR imaging of the patients were recorded and then evaluated as an inflammatory score (Inflam-score) and imaging feature score (Radio-score). Six Inflam-scores and 12 Radio-scores were determined from each patient by univariate analysis. Logistic regression was performed to select risk factors for MVI and establish a predictive nomogram. Decision curve analysis was applied to estimate the incremental value of the Inflam-score to the Radio-score for predicting MVI. RESULTS Four Radio-scores and 2 Inflam-scores, namely, larger tumor size, non-smooth tumor margin, presence of satellite nodules, presence of peritumoral enhance, higher neutrophil-lymphocyte ratio (NLR), and lower prognostic nutritional index (PNI), were significantly associated with MVI (p < 0.05). An MVI risk prediction nomogram was then constructed with an area under the curve (AUC) of 0.868 (95% CI 0.806-0.931). Adding Inflam-scores to Radio-scores improved the sensitivity of the model from 60.9 to 80.4% in receiver operating characteristic (ROC) curve analysis and led to a net benefit in decision curve analysis. CONCLUSION Systemic inflammatory biomarkers are complementary tools that provide additional benefit to conventional imaging estimation for predicting MVI in HCC patients.
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Paro A, Dalmacy D, Tslimigras DI, Cloyd J, Ejaz A, Pawlik TM. Association of County-Level Upward Economic Mobility with Stage at Diagnosis and Receipt of Curative-Intent Treatment among Patients with Hepatocellular Carcinoma. Ann Surg Oncol 2022; 29:5177-5185. [PMID: 35441305 DOI: 10.1245/s10434-022-11726-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Accepted: 03/21/2022] [Indexed: 12/18/2022]
Abstract
BACKGROUND Upward economic mobility represents the ability of children to surpass their parents financially and improve their economic status. The extent to which it contributes to socioeconomic disparities in health outcomes remains largely unknown. METHODS Patients diagnosed with hepatocellular carcinoma (HCC) in 2004-2015 were identified from the SEER-Medicare linked database. Information on county-level upward economic mobility was obtained from the Opportunity Atlas, and its impact on early-stage diagnosis (tumor size ≤ 5 cm, no nodal involvement or distant metastases, no major vascular invasion or extrahepatic extension) and receipt of curative-intent treatment (resection, transplantation, or ablation) was examined. RESULTS Among 9190 Medicare beneficiaries diagnosed with HCC, the majority were White (64.9%, n = 5965). Overall, 44.7% (n = 4105) of patients were diagnosed with early-stage HCC and 29.7% (n = 2731) underwent curative-intent treatment. While higher upward economic mobility was not associated with HCC diagnosis at an early stage (OR 0.94, 95% CI 0.83-1.06), patients with early-stage HCC from areas of high upward economic mobility had increased odds of undergoing curative-intent treatment (OR 1.25, 95% CI 1.03-1.51). Upward economic mobility had no impact on the likelihood to undergo curative-intent treatment for early-stage HCC among White (OR 1.15, 95% CI 0.91-1.45), Black (OR 1.94, 95% CI 0.85-4.45) or Asian patients (OR 0.77, 95% CI 0.44-1.36). In contrast, non-White patients other than Blacks or Asians diagnosed with early-stage HCC had markedly higher odds of receiving curative-intent treatment if the individual resided in an area characterized by higher versus lower upward economic mobility (OR 2.58, 95% CI 1.50-4.46). CONCLUSIONS While community-level economic mobility was not associated with stage of diagnosis, it affected the likelihood of undergoing curative-intent treatment for early-stage HCC, especially among minority patients other than Black or Asian patients.
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Affiliation(s)
- Alessandro Paro
- Department of Surgery, James Cancer Hospital and Solove Research Institute, The Ohio State University, Wexner Medical Center, Columbus, OH, USA
| | - Djhenne Dalmacy
- Department of Surgery, James Cancer Hospital and Solove Research Institute, The Ohio State University, Wexner Medical Center, Columbus, OH, USA
| | - Diamantis I Tslimigras
- Department of Surgery, James Cancer Hospital and Solove Research Institute, The Ohio State University, Wexner Medical Center, Columbus, OH, USA
| | - Jordan Cloyd
- Department of Surgery, James Cancer Hospital and Solove Research Institute, The Ohio State University, Wexner Medical Center, Columbus, OH, USA
| | - Aslam Ejaz
- Department of Surgery, James Cancer Hospital and Solove Research Institute, The Ohio State University, Wexner Medical Center, Columbus, OH, USA
| | - Timothy M Pawlik
- Department of Surgery, James Cancer Hospital and Solove Research Institute, The Ohio State University, Wexner Medical Center, Columbus, OH, USA.
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27
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Lee WC. Value of alpha-fetoprotein in hepatocellular carcinoma. Transl Gastroenterol Hepatol 2021; 6:52. [PMID: 34805574 DOI: 10.21037/tgh.2019.12.19] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2019] [Accepted: 12/23/2019] [Indexed: 12/21/2022] Open
Affiliation(s)
- Wei-Chen Lee
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan
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Yang D, Wu H, Nong W, Zheng M, Li A, Wang Y, Li M, Chen Q, Yuan S, Yu J, Liao W. A new model based on gamma-glutamyl transpeptidase to platelet ratio (GPR) predicts prognostic outcome after curative resection of solitary hepatocellular carcinoma. Clin Res Hepatol Gastroenterol 2021; 45:101509. [PMID: 33744828 DOI: 10.1016/j.clinre.2020.07.014] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Revised: 07/11/2020] [Accepted: 07/17/2020] [Indexed: 02/04/2023]
Abstract
BACKGROUND This study intends to explore the potential clinical value of gamma-glutamyl transpeptidase to platelet ratio (GPR) and the new multi-factor scoring model for recurrence and prognosis prediction in solitary HCC patients who received radical resection. METHODS This study retrospectively analyzed 295 HCC patients after curative resection. According to the Receiver Operating Characteristic (ROC) curve, the optimal cut-off value of GPR for predicting prognosis of HCC after resection was determined. The Kaplan Meier method and Cox regression analysis were performed to assess the important potential factors in the prognosis of HCC and determine the independent risk factors. Assign a value to each independent risk factor and establish a new scoring model. Then, using GPR and the new scoring model to evaluate overall survival (OS) and postoperative recurrence probability. RESULTS When GPR's cut-off value was selected as 0.30, its predictive efficiency for postoperative prognosis was more favorable than those of other cut-off values (0.76, 0.84 and 0.94). GPR, tumor size, microvascular invasion and neutrophil to lymphocyte ratio (NLR) were identified as independent prognostic predictors. Using these variables, a novel prognostic scoring model was devised and established to identify different levels of risk: high, intermediate and low risk groups. We found that patients with high GPR level and of high risk group would have a poorer OS and a higher recurrence rate after radical resection. CONCLUSIONS GPR may serve as a promising predictor for postoperative prognosis and recurrence probability of HCC, and the new prognostic scoring model may be available for postoperative management among HCC patients.
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Affiliation(s)
- Dongye Yang
- Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, 541001, Guangxi, PR China; Section of Academic Affairs of Guilin Medical University, Guilin, 541001, Guangxi, PR China
| | - Hongliang Wu
- Otolaryngology Head and Neck Surgery, Affiliated Hospital of Guilin Medical University, Guilin, 541001, Guangxi, PR China
| | - Wenxiong Nong
- Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, 541001, Guangxi, PR China
| | - Min Zheng
- Department of Cardiothoracic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, PR China
| | - Angui Li
- Department of Cardiothoracic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, PR China
| | - Yang Wang
- Department of Cardiothoracic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, PR China
| | - Mu Li
- Department of Cardiothoracic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, PR China
| | - Qian Chen
- Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, 541001, Guangxi, PR China
| | - Shengguang Yuan
- Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, 541001, Guangxi, PR China.
| | - Junxiong Yu
- Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, 541001, Guangxi, PR China.
| | - Weijia Liao
- Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, 541001, Guangxi, PR China.
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Liu G, Wu D, Wen Y, Cang S. Immune-associated molecular occurrence and prognosis predictor of hepatocellular carcinoma: an integrated analysis of GEO datasets. Bioengineered 2021; 12:5253-5265. [PMID: 34424809 PMCID: PMC8806587 DOI: 10.1080/21655979.2021.1962147] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second most common cause of cancer-related deaths worldwide. As immune response failure is the main factor in the occurrence and poor prognosis of HCC, our study aimed to develop an immune-associated molecular occurrence and prognosis predictor (IMOPP) of HCC. To that end, we discovered a 4-gene immune-associated gene signature: C-C motif chemokine ligand 14 (CCL14), kallikrein B1 (KLKB1), vasoactive intestinal peptide receptor 1 (VIPR1), and cluster of differentiation 4 (CD4). When tested on three cohorts as an immune-associated molecular occurrence predictor (IMOP), it had high sensitivity, specificity, and area under the receiver operating characteristics curve. When tested as an immune-associated molecular prognosis predictor (IMPP), it stratified the HCC prognosis for overall survival (Kaplan-Meier analysis, log rank P = 0.0016; Cox regression, HR = 1.832, 95% CI = 1.173-2.859, P = 0.008) and disease-free survival (Kaplan-Meier analysis, log rank P = 0.0227). IMPP also significantly correlated with the clinicopathological characteristics of HCC; integrating it with clinicopathological characteristics improved the accuracy of a nomogram for overall survival prediction (C-index: 0.7097 vs. 0.6631). In HCC tumor microenviroments, the proportion of CD8+ T cells significantly differed between IMOP-stratified groups. We conclude that IMOPP can potentially predict the occurrence of HCC in high-risk populations and improve prognostic accuracy by providing new biomarkers for risk stratification. In addition, we believe that the IMOP mechanism may be related to its effect on the proportion of CD8+ T cells in tumor-infiltrating lymphocytes.
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Affiliation(s)
- Guanjun Liu
- Department of Oncology, Henan Provincial People's Hospital, Zhengzhou, Henan, P.R. China.,Department of Oncology, People's Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China.,Department of Oncology, People's Hospital of Henan University, Zhengzhou, Henan, P.R. China
| | - Dongmei Wu
- Department of Radiotherapy, Xinxiang Center Hospital, Xinxiang, Henan, P.R. China
| | - Yiyang Wen
- Department of Oncology, Henan Provincial People's Hospital, Zhengzhou, Henan, P.R. China.,Department of Oncology, People's Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China.,Department of Oncology, People's Hospital of Henan University, Zhengzhou, Henan, P.R. China
| | - Shundong Cang
- Department of Oncology, Henan Provincial People's Hospital, Zhengzhou, Henan, P.R. China.,Department of Oncology, People's Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China.,Department of Oncology, People's Hospital of Henan University, Zhengzhou, Henan, P.R. China
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Wei T, Zhang XF, Xue F, Bagante F, Ratti F, Marques HP, Silva S, Soubrane O, Lam V, Poultsides GA, Popescu I, Grigorie R, Alexandrescu S, Martel G, Workneh A, Guglielmi A, Hugh T, Aldrighetti L, Endo I, Pawlik TM. Multi-Institutional Development and External Validation of a Nomogram for Prediction of Extrahepatic Recurrence After Curative-Intent Resection for Hepatocellular Carcinoma. Ann Surg Oncol 2021; 28:7624-7633. [PMID: 34019181 DOI: 10.1245/s10434-021-10142-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Accepted: 04/26/2021] [Indexed: 12/24/2022]
Abstract
BACKGROUNDS Extrahepatic recurrence of hepatocellular carcinoma (HCC) after surgical resection is associated with unfavorable prognosis. The objectives of the current study were to identify the risk factors and develop a nomogram for the prediction of extrahepatic recurrence after initial curative surgery. METHODS A total of 635 patients who underwent curative-intent resection for HCC between 2000 and 2017 were identified from an international multi-institutional database. The clinicopathological characteristics, risk factors, and long-term survival of patients with extrahepatic recurrence were analyzed. A nomogram for the prediction of extrahepatic recurrence was established and validated in 144 patients from an external cohort. RESULTS Among the 635 patients in the derivative cohort, 283 (44.6%) experienced recurrence. Among patients who recurred, 80 (28.3%) patients had extrahepatic ± intrahepatic recurrence, whereas 203 (71.7%) had intrahepatic recurrence only. Extrahepatic recurrence was associated with more advanced initial tumor characteristics, early recurrence, and worse prognosis versus non-extrahepatic recurrence. A nomogram for the prediction of extrahepatic recurrence was developed using the β-coefficients from the identified risk factors, including neutrophil-to-lymphocyte ratio, multiple lesions, tumor size, and microvascular invasion. The nomogram demonstrated good ability to predict extrahepatic recurrence (c-index: training cohort 0.786; validation cohort: 0.845). The calibration plots demonstrated good agreement between estimated and observed extrahepatic recurrence (p = 0.658). CONCLUSIONS An externally validated nomogram was developed with good accuracy to predict extrahepatic recurrence following curative-intent resection of HCC. This nomogram may help identify patients at high risk of extrahepatic recurrence and guide surveillance protocols as well as adjuvant treatments.
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Affiliation(s)
- Tao Wei
- Department of Hepatobiliary Surgery and Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.,Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xu-Feng Zhang
- Department of Hepatobiliary Surgery and Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.,Division of Surgical Oncology, Department of Surgery, Medical Center and James Comprehensive Cancer Center, The Ohio State University Wexner, Columbus, OH, USA
| | - Feng Xue
- Department of Hepatobiliary Surgery and Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Fabio Bagante
- Division of Surgical Oncology, Department of Surgery, Medical Center and James Comprehensive Cancer Center, The Ohio State University Wexner, Columbus, OH, USA.,Department of Surgery, University of Verona, Verona, Italy
| | | | - Hugo P Marques
- Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal
| | - Silvia Silva
- Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal
| | - Olivier Soubrane
- Department of Hepatobiliopancreatic Surgery, APHP, Beaujon Hospital, Clichy, France
| | - Vincent Lam
- Department of Surgery, Westmead Hospital, Sydney, NSW, Australia
| | | | - Irinel Popescu
- Department of Surgery, Fundeni Clinical Institute, Bucharest, Romania
| | - Razvan Grigorie
- Department of Surgery, Fundeni Clinical Institute, Bucharest, Romania
| | | | | | - Aklile Workneh
- Department of Surgery, University of Ottawa, Ottawa, ON, Canada
| | | | - Tom Hugh
- Department of Surgery, School of Medicine, The University of Sydney, Sydney, NSW, Australia
| | | | - Itaru Endo
- Yokohama City University School of Medicine, Yokohama, Japan
| | - Timothy M Pawlik
- Division of Surgical Oncology, Department of Surgery, Medical Center and James Comprehensive Cancer Center, The Ohio State University Wexner, Columbus, OH, USA.
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31
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Zou J, Li S, Wang Q, Mei J, Lu L, Lin W, Wen Y, Li Y, Wei W, Guo R. Surgical strategies for hepatocellular carcinoma located in the left lateral lobe: A propensity score-matched and prognostic nomogram study. Cancer Med 2021; 10:3274-3287. [PMID: 33932132 PMCID: PMC8124126 DOI: 10.1002/cam4.3894] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Revised: 03/09/2021] [Accepted: 03/21/2021] [Indexed: 12/24/2022] Open
Abstract
PURPOSE For hepatocellular carcinoma (HCC) located in the left lateral lobe, the optimal surgical procedure is still controversial. This study aimed to optimize surgical strategies and to construct a nomogram to predict the postoperative survival of patients with HCC. METHODS Between 1 January 2005 and 30 September 2018, a total of 493 patients were enrolled. Propensity score matching (PSM) was performed between the left lateral lobectomy (LLL) and left hepatectomy (LH) groups (1:1). The study endpoints were overall survival (OS), recurrence-free survival (RFS), and safety. A nomogram was generated using a multivariate Cox proportional hazards model. The discriminative ability and calibration of the nomogram were evaluated using C-statistics and calibration plots. RESULTS After matching, 87 pairs were included. The LH group had better 1-, 3-, and 5-year OS rates than the LLL group (88%, 73%, and 69% vs. 73%, 57%, and 49%, respectively; p = 0.017). The 1-, 3-, and 5-year RFS rates of the LH group were similar to those of the LLL group (64%, 49%, and 46% vs. 63%, 51%, and 42%, respectively; p = 0.652). There were no significant differences in postoperative complications. Eight factors were integrated into the nomogram and it had good discriminative ability and calibration. CONCLUSION Our data revealed that compared to LLL, LH may result in better OS and have similar postoperative complications for HCC. The nomogram may serve as a practical tool for the individual prognostic evaluation of patients with HCC.
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Affiliation(s)
- Jingwen Zou
- Department of Liver SurgerySun Yat‐sen University Cancer CenterGuangzhouP. R. China
- State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhouP. R. China
| | - Shaohua Li
- Department of Liver SurgerySun Yat‐sen University Cancer CenterGuangzhouP. R. China
- State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhouP. R. China
| | - Qiaoxuan Wang
- State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhouP. R. China
- Department of Radiation OncologySun Yat‐sen University Cancer CenterGuangzhouP. R. China
| | - Jie Mei
- Department of Liver SurgerySun Yat‐sen University Cancer CenterGuangzhouP. R. China
- State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhouP. R. China
| | - Lianghe Lu
- Department of Liver SurgerySun Yat‐sen University Cancer CenterGuangzhouP. R. China
- State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhouP. R. China
| | - Wenping Lin
- Department of Liver SurgerySun Yat‐sen University Cancer CenterGuangzhouP. R. China
- State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhouP. R. China
| | - Yuhua Wen
- Department of Liver SurgerySun Yat‐sen University Cancer CenterGuangzhouP. R. China
- State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhouP. R. China
| | - Yuechao Li
- Department of Liver SurgerySun Yat‐sen University Cancer CenterGuangzhouP. R. China
- State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhouP. R. China
| | - Wei Wei
- Department of Liver SurgerySun Yat‐sen University Cancer CenterGuangzhouP. R. China
- State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhouP. R. China
| | - Rongping Guo
- Department of Liver SurgerySun Yat‐sen University Cancer CenterGuangzhouP. R. China
- State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhouP. R. China
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Preoperative prediction of pathologic grade of HCC on gadobenate dimeglumine-enhanced dynamic MRI. Eur Radiol 2021; 31:7584-7593. [PMID: 33860826 DOI: 10.1007/s00330-021-07891-0] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2020] [Revised: 03/04/2021] [Accepted: 03/15/2021] [Indexed: 02/08/2023]
Abstract
PURPOSE To evaluate the value of gadobenate dimeglumine-enhanced MRI in predicting the pathologic grade of hepatocellular carcinoma (HCC). MATERIALS AND METHODS Patients with pathologically proven HCC who underwent preoperative gadobenate dimeglumine-enhanced dynamic MRI were included. Two radiologists blinded to pathology results evaluated images in consensus. Lesions were evaluated quantitatively in terms of ratio of enhancement (RE), and qualitatively based on image features related to tumor aggressiveness. Logistic regression and ROC analyses were used to determine the value of these parameters to predict pathologic grade. RESULTS In total, 221 patients (194 males, 27 females, aged 52.9 ± 11.7 years) with 49 poorly differentiated HCCs and 172 well/moderately differentiated HCCs were evaluated. Features significantly related to poorer pathologic grade at univariate analysis included lower RE in the early arterial phase (EAP) (p = 0.001), nonsmooth margins (p = 0.001), absence of capsule (p < 0.001), arterial peritumoral hyperenhancement (p < 0.001), higher AFP (p = 0.004), multiple tumors (p = 0.026), and larger tumor size (p = 0.028). At multivariate analysis, lower RE (EAP) (OR = 0.144, p = 0.002), absence of capsule (OR = 0.281, p = 0.004), and arterial peritumoral hyperenhancement (OR = 4.117, p < 0.001) were independent predictive factors for poorer pathologic grade. ROC analysis showed lower RE (EAP) was predictive of poorer pathologic grade (AUC = 0.667). AUC increased to 0.797 when combined with absence of capsule and presence of peritumoral hyperenhancement. CONCLUSIONS Lower RE (EAP), absence of capsule, and arterial peritumoral hyperenhancement were predictive biomarkers for poorer pathologic grade of HCC on gadobenate dimeglumine-enhanced dynamic MRI. KEY POINTS • Gadobenate dimeglumine-enhanced dynamic MRI was a useful quantitative biomarker for preoperative prediction of pathologic grade in patients with HCC. • Lower RE in the early arterial phase, absence of capsule, and arterial peritumoral hyperenhancement were potential imaging indicators for preoperative prediction of poorer pathologic grade of HCC on gadobenate dimeglumine-enhanced MRI. • A lower RE in the early arterial phase was effective at predicting poorer pathologic grade of HCCs but prediction is improved when combined with absence of capsule and presence of peritumoral hyperenhancement.
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Preoperative immune landscape predisposes adverse outcomes in hepatocellular carcinoma patients with liver transplantation. NPJ Precis Oncol 2021; 5:27. [PMID: 33772139 PMCID: PMC7997876 DOI: 10.1038/s41698-021-00167-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2020] [Accepted: 03/03/2021] [Indexed: 01/15/2023] Open
Abstract
Immune class in hepatocellular carcinoma (HCC) has been shown to possess immunogenic power; however, how preestablished immune landscapes in premalignant and early HCC stages impact the clinical outcomes of HCC patients remains unexplored. We sequenced bulk transcriptomes for 62 malignant tumor samples from a Korean HCC cohort in which 38 patients underwent total hepatectomy, as well as for 15 normal and 47 adjacent nontumor samples. Using in silico deconvolution of expression mixtures, 22 immune cell fractions for each sample were inferred, and validated with immune cell counting by immunohistochemistry. Cell type-specific immune signatures dynamically shifted from premalignant stages to the late HCC stage. Total hepatectomy patients displayed elevated immune infiltration and prolonged disease-free survival compared to the partial hepatectomy patients. However, patients who exhibited an infiltration of regulatory T cells (Tregs) during the pretransplantation period displayed a high risk of tumor relapse with suppressed immune responses, and pretreatment was a potential driver of Treg infiltration in the total hepatectomy group. Treg infiltration appeared to be independent of molecular classifications based on transcriptomic data. Our study provides not only comprehensive immune signatures in adjacent nontumor lesions and early malignant HCC stages but also clinical guidance for HCC patients who will undergo liver transplantation.
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Chen HL, Chen YH, Du L, Song YP, Zhu B. Elevated serum alpha-fetoprotein levels are associated with poor prognosis of hepatocellular carcinoma after surgical resection: A systematic review and meta-analysis. Arab J Gastroenterol 2021; 22:12-22. [PMID: 33551350 DOI: 10.1016/j.ajg.2020.09.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2019] [Revised: 06/22/2020] [Accepted: 09/08/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND STUDY AIMS The relationship between the alpha-fetoprotein (AFP) level and the prognosis of hepatocellular carcinoma (HCC) after surgical resection remains unknown. This study aims to assess this relationship. PATIENTS AND METHODS PubMed and Web of Science were systematically utilised. Meta-analysis was conducted for the outcomes of the recurrence-free survival (RFS) and the overall survival (OS) by comparing the high AFP group with the low AFP group. RESULTS The studies included 61 manuscripts with 35,461 patients. The summary hazard ratio (HR) for RFS was 1.501 (95% CI 1.355-1.662; Z = 7.81, P < 0.00001) when comparing the high AFP group with the low AFP group. Sensitivity analysis only included adjusted HRs, with the summary HR being 1.563 (95% CI 1.381-1.768; Z = 7.10, P < 0.00001). The summary HR for OS was 1.565 (95% CI 1.439-1.701; Z = 10.52, P < 0.00001) when comparing two AFP groups. Sensitivity analysis showed that the summary HR was 1.611 (95% CI 1.456-1.782; Z = 9.24, P < 0.00001). CONCLUSION Our meta-analysis indicated that elevated serum AFP levels are associated with poor prognosis of HCC after surgical resection.
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Affiliation(s)
- Hong-Lin Chen
- Nantong University, School of Public Health, Nantong City, Jiangsu Province, China
| | - Yu-Hua Chen
- Nantong Health College of Jiangsu Province, Nantong City, Jiangsu Province, China
| | - Lin Du
- Nantong University, School of Public Health, Nantong City, Jiangsu Province, China
| | - Yi-Ping Song
- Nantong University, School of Public Health, Nantong City, Jiangsu Province, China
| | - Bin Zhu
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Nantong University, China.
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Vitiello GA, Wang A, Lee RM, Russell MC, Yopp A, Ryon EL, Goel N, Luu S, Hsu C, Silberfein E, Correa-Gallego C, Berman RS, Lee AY. Surgical resection of early stage hepatocellular carcinoma improves patient survival at safety net hospitals. J Surg Oncol 2021; 123:963-969. [PMID: 33497478 DOI: 10.1002/jso.26381] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Revised: 12/30/2020] [Accepted: 01/04/2021] [Indexed: 12/22/2022]
Abstract
BACKGROUND AND OBJECTIVES Surgical resection is indicated for hepatocellular carcinoma (HCC) patients with Child A cirrhosis. We hypothesize that surgical intervention and survival are limited by advanced HCC presentation at safety net hospitals (SNHs) versus academic medical centers (AMCs). METHODS Patients with HCC and Child A cirrhosis in the US Safety Net Collaborative (2012-2014) were evaluated. Demographics, clinicopathologic features, operative characteristics, and outcomes were compared between SNHs and AMCs. Liver transplantation was excluded. Kaplan-Meier and Cox proportional-hazards models were used to identify the effect of surgery on overall (OS). RESULTS A total of 689 Child A patients with HCC were identified. SNH patients frequently presented with T3/T4 stage (35% vs. 24%) and metastases (17% vs. 8%; p < .05). SNH patients were as likely to undergo surgery as AMC patients (17% vs. 18%); however, SNH patients were younger (56 vs. 64 years), underwent minor hepatectomy (65% vs. 38%), and frequently harbored well-differentiated tumors (23% vs. 2%; p < .05). On multivariate analysis, surgical resection and stage, but not hospital type, were associated with improved OS. CONCLUSIONS Although SNH patients present with advanced HCC, survival outcomes for early stage HCC are similar at SNHs and AMCs. Identifying barriers to early diagnosis at SNH may increase surgical candidacy and improve outcomes.
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Affiliation(s)
- Gerardo A Vitiello
- Department of Surgery, New York University Langone Health, New York, New York, USA
| | - Annie Wang
- Department of Surgery, New York University Langone Health, New York, New York, USA
| | - Rachel M Lee
- Department of Surgery, Emory University, Atlanta, Georgia, USA
| | - Maria C Russell
- Department of Surgery, Emory University, Atlanta, Georgia, USA
| | - Adam Yopp
- Department of Surgery, University of Texas Southwestern Medical School, Dallas, Texas, USA
| | - Emily L Ryon
- Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Neha Goel
- Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Sommer Luu
- Department of Surgery, Baylor College of Medicine, Houston, Texas, USA
| | - Cary Hsu
- Department of Surgery, Baylor College of Medicine, Houston, Texas, USA
| | - Eric Silberfein
- Department of Surgery, Baylor College of Medicine, Houston, Texas, USA
| | | | - Russell S Berman
- Department of Surgery, New York University Langone Health, New York, New York, USA
| | - Ann Y Lee
- Department of Surgery, New York University Langone Health, New York, New York, USA
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36
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Yan B, Su BB, Bai DS, Qian JJ, Zhang C, Jin SJ, Jiang GQ. A practical nomogram and risk stratification system predicting the cancer-specific survival for patients with early hepatocellular carcinoma. Cancer Med 2020; 10:496-506. [PMID: 33280269 PMCID: PMC7877377 DOI: 10.1002/cam4.3613] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2020] [Revised: 10/26/2020] [Accepted: 10/29/2020] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Our purpose was to establish and validate a nomogram model in early hepatocellular carcinoma (HCC) patients for predicting the cancer-specific survival (CSS). METHODS We extracted eligible data of relevant patients between 2010 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database. Further, we divided all patients into two groups (training and validation cohorts) at random (7:3). Nomogram was established using effective risk factors based on univariate and multivariate analysis. The effective performance of nomogram was evaluated using concordance index (C-index), calibration plots, decision curve analysis (DCA), and receiver operating characteristic curve (ROC). RESULTS We selected 3620 patients with early HCC including the training cohort (70%, 2536) and the validation cohort (30%, 1084). The nomogram-related C-indexes were 0.755 (95% CI: 0.739-0.771) and 0.737 (95% CI: 0.712-0.762), in the training and validation cohorts, respectively. The calibration plots showed good consistency of 3-and 5-year CSS between the actual observation and the nomogram prediction. The 3-, 5-year DCA curves also indicated that the nomogram has excellent clinical utility. The 3-, 5-year area under curve (AUC) of ROC in the training cohort were 0.783, 0.779, respectively, and 0.767, 0.766 in the validation cohort, respectively. With the establishment of nomogram, a risk stratification system was also established that could divide all patients into three risk groups, and the CSS in different groups (i.e., low risk, intermediate risk, and high risk) had a good regional division. CONCLUSIONS We developed a practical nomogram in early HCC patients for predicting the CSS, and a risk stratification system follow arisen, which provided an applicable tool for clinical management.
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Affiliation(s)
- Bing Yan
- Department of Hepatobiliary Surgery, Clinical Medical College, Yangzhou University, Yangzhou, China.,Department of Hepatobiliary Surgery, The Second Clinical College, Dalian Medical University, Dalian, China
| | - Bing-Bing Su
- Department of Hepatobiliary Surgery, Clinical Medical College, Yangzhou University, Yangzhou, China
| | - Dou-Sheng Bai
- Department of Hepatobiliary Surgery, Clinical Medical College, Yangzhou University, Yangzhou, China
| | - Jian-Jun Qian
- Department of Hepatobiliary Surgery, Clinical Medical College, Yangzhou University, Yangzhou, China
| | - Chi Zhang
- Department of Hepatobiliary Surgery, Clinical Medical College, Yangzhou University, Yangzhou, China
| | - Sheng-Jie Jin
- Department of Hepatobiliary Surgery, Clinical Medical College, Yangzhou University, Yangzhou, China
| | - Guo-Qing Jiang
- Department of Hepatobiliary Surgery, Clinical Medical College, Yangzhou University, Yangzhou, China
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Gelli M, Sebagh M, Porcher R, Romanelli E, Vibert E, Sa Cunha A, Castaing D, Rosmorduc O, Samuel D, Adam R, Cherqui D. Liver Resection for Early Hepatocellular Carcinoma: Preoperative Predictors of Non Transplantable Recurrence and Implications for Treatment Allocation. Ann Surg 2020; 272:820-826. [PMID: 32833755 DOI: 10.1097/sla.0000000000004259] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
BACKGROUND AND AIMS LR and LT are the standard curative options for early HCC. LT provides best long-term survival but is limited by organ shortage. LR, readily available, is hampered by high recurrence rates. Salvage liver transplantation is an efficient treatment of recurrences within criteria. The aim of the study was to identify preoperative predictors of non transplantable recurrence (NTR) to improve patient selection for upfront LR or LT at initial diagnosis. STUDY DESIGN Consecutive LR for transplantable HCC between 2000 and 2015 were studied. A prediction model for NTR based on preoperative variables was developed using sub-distribution hazard ratio after multiple imputation and internal validation by bootstrapping. Model performance was evaluated by the concordance index after correction for optimism. RESULTS A total of 148 patients were included. Five-year overall survival and recurrence free survival were 73.6% and 29.3%, respectively (median follow-up 45.8 months). Recurrence rate was 54.8%. NTR rate was 38.2%. Preoperative model for NTR identified >1 nodule [sub-distribution hazard ratio 2.35 95% confidence interval (CI) 1.35-4.09], AFP >100 ng/mL (2.14 95% CI 1.17-3.93), and F4 fibrosis (1.93 95% CI 1.03-3.62). The apparent concordance index of the model was 0.664 after correction for optimism. In the presence of 0, 1, and ≥2 factors, NTR rates were 2.6%, 22.7%, and 40.9%, respectively. The number of prognostic factors was significantly associated with the pattern of recurrence (P = 0.001) and 5-year recurrence free survival (P < 0.001). CONCLUSIONS Cirrhosis, >1 nodule, and AFP >100 ng/mL were identified as preoperative predictors of NTR. In the presence of 2 factors or more upfront transplantation should be probably preferred to resection in regard of organ availability. Other patients are good candidates for LR and salvage liver transplantation should be encouraged in eligible patients with recurrence.
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Affiliation(s)
- Maximiliano Gelli
- Hepatobiliary Center Paul Brousse Hospital, APHP-Université Paris Saclay, Villejuif, France
| | - Mylène Sebagh
- Department of Pathology, APHP - Université Paris Saclay, Hôpital Paul Brousse, Villejuif, France
| | - Raphaël Porcher
- Centre de Recherche Épidémiologie et Statistique (CRESS-UMR1153) Université Paris Descartes-Hôpital Hôtel-Dieu, Paris, France
| | - Elena Romanelli
- Hepatobiliary Center Paul Brousse Hospital, APHP-Université Paris Saclay, Villejuif, France
| | - Eric Vibert
- Hepatobiliary Center Paul Brousse Hospital, APHP-Université Paris Saclay, Villejuif, France
| | - Antonio Sa Cunha
- Hepatobiliary Center Paul Brousse Hospital, APHP-Université Paris Saclay, Villejuif, France
| | - Denis Castaing
- Hepatobiliary Center Paul Brousse Hospital, APHP-Université Paris Saclay, Villejuif, France
| | - Olivier Rosmorduc
- Hepatobiliary Center Paul Brousse Hospital, APHP-Université Paris Saclay, Villejuif, France
| | - Didier Samuel
- Hepatobiliary Center Paul Brousse Hospital, APHP-Université Paris Saclay, Villejuif, France
| | - René Adam
- Hepatobiliary Center Paul Brousse Hospital, APHP-Université Paris Saclay, Villejuif, France
| | - Daniel Cherqui
- Hepatobiliary Center Paul Brousse Hospital, APHP-Université Paris Saclay, Villejuif, France
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Zhang C, Yang M, Ericsson AC. The Potential Gut Microbiota-Mediated Treatment Options for Liver Cancer. Front Oncol 2020; 10:524205. [PMID: 33163393 PMCID: PMC7591398 DOI: 10.3389/fonc.2020.524205] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2020] [Accepted: 09/21/2020] [Indexed: 02/06/2023] Open
Abstract
Primary liver cancer is one of the leading causes of cancer death worldwide. Surgical and non-surgical treatments are optional for liver cancer therapy based on the cancer stage. Accumulating studies show that the gut-liver axis influences the progression of liver diseases, including liver inflammation, fibrosis, cirrhosis, and cancer. However, the role of gut microbiota and their derived components and metabolites in liver cancer remains to be further clarified. In this review, we discuss the roles of gut microbiota and specific bacterial species in HCC and the strategies to modulate gut microbiota to improve antitumor therapy. Given the limitation of current treatments, gut microbiota-mediated therapy is a potential option for HCC treatment, including fiber diet and vegetable diet, antimicrobials, probiotics, and pharmaceutical inhibitors. Also, gut microbiota can be used as a marker for early diagnosis of HCC. HCC occurs dependent on various environmental and genetic factors, including diet and sex. Furthermore, gut microbiota impacts the immunotherapy of HCC treatment. Therefore, a better understanding of the role of the gut-liver axis in liver cancer is critically important to improve therapeutic efficacy.
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Affiliation(s)
- Chunye Zhang
- Department of Veterinary Pathobiology, University of Missouri, Columbia, MO, United States
| | - Ming Yang
- Department of Surgery, University of Missouri, Columbia, MO, United States
| | - Aaron C. Ericsson
- Department of Veterinary Pathobiology, University of Missouri, Columbia, MO, United States
- University of Missouri Metagenomics Center, University of Missouri, Columbia, MO, United States
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Zeng J, Lin K, Liu H, Huang Y, Guo P, Zeng Y, Zeng J, Liu J. Prognosis Factors of Young Patients Undergoing Curative Resection for Hepatitis B Virus-Related Hepatocellular Carcinoma: A Multicenter Study. Cancer Manag Res 2020; 12:6597-6606. [PMID: 32848453 PMCID: PMC7425652 DOI: 10.2147/cmar.s261368] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2020] [Accepted: 06/30/2020] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND The prognosis of young and older patients with hepatocellular carcinoma (HCC) is controversial. We aim to compare the clinicopathological features and prognosis of young (age ≤40 years) versus older patients (aged >40 years) with hepatitis B virus (HBV)-related HCC after curative resection. METHODS A total of 4504 patients with HBV-related HCC who underwent curative resection were included in this study and divided into young group (n=699) and older group (n=3805). Subgroup analyses were conducted to compare. Independent risk factors were identified by Cox regression analysis. RESULTS Young patients had better ALBI grade, lower rates of liver cirrhosis, higher rates of elevated serum AFP levels, larger tumor size, higher rates of microvascular invasion and macrovascular invasion, higher rates of Edmondson grade III-IV, lower rates of tumor capsular, more advanced AJCC TNM stages and more advanced BCLC stages than older patients (All p<0.05). Meanwhile, young patients had a worse overall survival (OS) rate (p=0.0091) and a worse recurrence-free survival (RFS) rate (p=0.045) than older patients. Multivariate analysis revealed that AFP, resection margin, tumor size, tumor capsular, and macrovascular invasion were associated with OS. The independent risk factors associated with RFS were ALB, tumor size, microvascular invasion, and macrovascular invasion. CONCLUSION Young patients had better liver function, more aggressive tumor characteristics, and worse prognosis than older patients. A tumor size of ≥5 cm and macrovascular invasion were associated with poor OS and RFS in young patients. If tumors could be detected at the early stage by more frequent surveillance, long-term survival can be expected in the young patients.
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Affiliation(s)
- Jianxing Zeng
- Department of Hepatic Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou350025, People’s Republic of China
- The First Affiliated Hospital of Fujian Medical University, Fuzhou350005, People’s Republic of China
- The Liver Center of Fujian Province, Fujian Medical University, Fuzhou350025, People’s Republic of China
| | - Kongying Lin
- Southeast Big Data Institute of Hepatobiliary Health, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou350025, People’s Republic of China
| | - Huocheng Liu
- Department of Hepatic Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou350025, People’s Republic of China
| | - Yao Huang
- Department of Hepatic Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou350025, People’s Republic of China
- The First Affiliated Hospital of Fujian Medical University, Fuzhou350005, People’s Republic of China
- The Liver Center of Fujian Province, Fujian Medical University, Fuzhou350025, People’s Republic of China
| | - Pengfei Guo
- Southeast Big Data Institute of Hepatobiliary Health, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou350025, People’s Republic of China
| | - Yongyi Zeng
- Department of Hepatic Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou350025, People’s Republic of China
- The First Affiliated Hospital of Fujian Medical University, Fuzhou350005, People’s Republic of China
- The Liver Center of Fujian Province, Fujian Medical University, Fuzhou350025, People’s Republic of China
| | - Jinhua Zeng
- Department of Hepatic Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou350025, People’s Republic of China
- The First Affiliated Hospital of Fujian Medical University, Fuzhou350005, People’s Republic of China
- The Liver Center of Fujian Province, Fujian Medical University, Fuzhou350025, People’s Republic of China
| | - Jingfeng Liu
- Department of Hepatic Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou350025, People’s Republic of China
- The First Affiliated Hospital of Fujian Medical University, Fuzhou350005, People’s Republic of China
- The Liver Center of Fujian Province, Fujian Medical University, Fuzhou350025, People’s Republic of China
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Ruff SM, Rothermel LD, Diggs LP, Wach MM, Ayabe RI, Martin SP, Boulware D, Anaya D, Davis JL, Mullinax JE, Hernandez JM. Tumor grade may be used to select patients with multifocal hepatocellular carcinoma for resection. HPB (Oxford) 2020; 22:1004-1010. [PMID: 31734237 PMCID: PMC7771330 DOI: 10.1016/j.hpb.2019.10.1531] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2019] [Revised: 07/23/2019] [Accepted: 10/13/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND While resection is a recommended treatment for patients with stage 1 hepatocellular carcinoma (HCC), it remains controversial for multifocal disease. We sought to identify patients with multifocal HCC with survival after resection similar to patients with clinical stage 1 HCC. METHODS The National Cancer Database was queried to identify patients that underwent resection for HCC. RESULTS In this study, 2990 patients with a single tumor, and 1087 patients with multifocal disease confined to one lobe underwent resection. In the multifocal cohort, patients with clinical stage 3 (HR 1.54, CI 1.31-1.81, p < 0.0001) or 4 (HR 2.27, CI 1.57-3.29, p < 0.0001) disease, and those with moderately-differentiated (HR 1.32, CI 1.06-1.64, p = 0.012) or poorly differentiated/undifferentiated tumors (HR 1.53, CI 1.20-1.95, p = 0.0006) were associated with worse overall survival (OS). There was no difference in OS between patients with well-differentiated clinical stage 2 multifocal HCC and those with all grades of clinical stage 1 HCC (median of 84.8 (CI 66.3-107.2) vs 76.2 months (CI 71.2-81.3), respectively, p = 0.356). CONCLUSIONS Patients with well-differentiated, clinical stage 2 multifocal HCC confined to one lobe experience similar OS following hepatic resection to patients with clinical stage 1 disease. These findings may impact the management of select patients with multifocal HCC.
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Affiliation(s)
- Samantha M Ruff
- Surgical Oncology Program, National Cancer Institute, National Institutes of Health, 10 Center Drive Bethesda, MD, 20892, USA
| | - Luke D Rothermel
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center & Research Institute, 12902 USF Magnolia Drive Tampa, FL, 33612, USA
| | - Laurence P Diggs
- Surgical Oncology Program, National Cancer Institute, National Institutes of Health, 10 Center Drive Bethesda, MD, 20892, USA
| | - Michael M Wach
- Surgical Oncology Program, National Cancer Institute, National Institutes of Health, 10 Center Drive Bethesda, MD, 20892, USA
| | - Reed I Ayabe
- Surgical Oncology Program, National Cancer Institute, National Institutes of Health, 10 Center Drive Bethesda, MD, 20892, USA
| | - Sean P Martin
- Surgical Oncology Program, National Cancer Institute, National Institutes of Health, 10 Center Drive Bethesda, MD, 20892, USA
| | - David Boulware
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center & Research Institute, 12902 USF Magnolia Drive Tampa, FL, 33612, USA
| | - Daniel Anaya
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center & Research Institute, 12902 USF Magnolia Drive Tampa, FL, 33612, USA
| | - Jeremy L Davis
- Surgical Oncology Program, National Cancer Institute, National Institutes of Health, 10 Center Drive Bethesda, MD, 20892, USA
| | - John E Mullinax
- Sarcoma Department, H. Lee Moffitt Cancer Center & Research Institute, 12902 USF Magnolia Drive Tampa, FL, 33612, USA
| | - Jonathan M Hernandez
- Surgical Oncology Program, National Cancer Institute, National Institutes of Health, 10 Center Drive Bethesda, MD, 20892, USA.
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Ling YH, Chen JW, Wen SH, Huang CY, Li P, Lu LH, Mei J, Li SH, Wei W, Cai MY, Guo RP. Tumor necrosis as a poor prognostic predictor on postoperative survival of patients with solitary small hepatocellular carcinoma. BMC Cancer 2020; 20:607. [PMID: 32600297 PMCID: PMC7325084 DOI: 10.1186/s12885-020-07097-5] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2019] [Accepted: 06/22/2020] [Indexed: 02/08/2023] Open
Abstract
Background Small hepatocellular carcinoma (sHCC) is a special subtype of HCC with the maximum tumor diameter ≤ 3 cm and excellent long-term outcomes. Surgical resection or radiofrequency ablation provides the greatest chance for cure; however, many patients still undergo tumor recurrence after primary treatment. To date, there is no clinical applicable method to assess biological aggressiveness in solitary sHCC. Methods In the current study, we retrospectively evaluated tumor necrosis of 335 patients with solitary sHCC treated with hepatectomy between December 1998 and 2010 from Sun Yat-sen University Cancer Center. Results The presence of tumor necrosis was observed in 157 of 335 (46.9%) sHCC patients. Further correlation analysis showed that tumor necrosis was significantly correlated with tumor size and vascular invasion (P = 0.026, 0.003, respectively). The presence of tumor necrosis was associated closely with poorer cancer-specific overall survival (OS) and recurrence-free survival (RFS) as evidenced by univariate (P < 0.001; hazard ratio, 2.821; 95% CI, 1.643–4.842) and multivariate analysis (P = 0.005; hazard ratio, 2.208; 95% CI, 1.272–3.833). Notably, the combined model by tumor necrosis, vascular invasion and tumor size can significantly stratify the risk for RFS and OS and improve the ability to discriminate sHCC patients’ outcomes (P < 0.0001 for both). Conclusions Our results provide evidence that tumor necrosis has the potential to be a parameter for cancer aggressiveness in solitary sHCC. The combined prognostic model may be a useful tool to identify solitary sHCC patients with worse outcomes.
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Affiliation(s)
- Yi-Hong Ling
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.,Department of Pathology, Sun Yat-sen University Cancer Center, No. 651, Dongfeng Road East, Guangzhou, 510060, China
| | - Jie-Wei Chen
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.,Department of Pathology, Sun Yat-sen University Cancer Center, No. 651, Dongfeng Road East, Guangzhou, 510060, China
| | - Shi-Hong Wen
- Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Chao-Yun Huang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.,Department of Pathology, Sun Yat-sen University Cancer Center, No. 651, Dongfeng Road East, Guangzhou, 510060, China
| | - Peng Li
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.,Department of Pathology, Sun Yat-sen University Cancer Center, No. 651, Dongfeng Road East, Guangzhou, 510060, China
| | - Liang-He Lu
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.,Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, No. 651, Dongfeng Road East, Guangzhou, 510060, China
| | - Jie Mei
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.,Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, No. 651, Dongfeng Road East, Guangzhou, 510060, China
| | - Shao-Hua Li
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.,Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, No. 651, Dongfeng Road East, Guangzhou, 510060, China
| | - Wei Wei
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.,Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, No. 651, Dongfeng Road East, Guangzhou, 510060, China
| | - Mu-Yan Cai
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China. .,Department of Pathology, Sun Yat-sen University Cancer Center, No. 651, Dongfeng Road East, Guangzhou, 510060, China.
| | - Rong-Ping Guo
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China. .,Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, No. 651, Dongfeng Road East, Guangzhou, 510060, China.
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Chen Q, Tan L, Jin Z, Liu Y, Zhang Z. Downregulation of CRABP2 Inhibit the Tumorigenesis of Hepatocellular Carcinoma In Vivo and In Vitro. BIOMED RESEARCH INTERNATIONAL 2020; 2020:3098327. [PMID: 32685464 PMCID: PMC7334762 DOI: 10.1155/2020/3098327] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Accepted: 06/16/2020] [Indexed: 12/14/2022]
Abstract
Cellular retinoic acid-binding protein 2 (CRABP2) binds retinoic acid (RA) in the cytoplasm and transports it into the nucleus, allowing for the regulation of specific downstream signal pathway. Abnormal expression of CRABP2 has been detected in the development of several tumors. However, the role of CRABP2 in hepatocellular carcinoma (HCC) has never been revealed. The current study aimed to investigate the role of CRABP2 in HCC and illuminate the potential molecular mechanisms. The expression of CRABP2 in HCC tissues and cell lines was detected by western blotting and immunohistochemistry assays. Our results demonstrated that the expression levels of CRABP2 in HCC tissues were elevated with the tumor stage development, and it was also elevated in HCC cell lines. To evaluate the function of CRABP2, shRNA-knockdown strategy was used in HCC cells. Cell proliferation, metastasis, and apoptosis were analyzed by CCK-8, EdU staining, transwell, and flow cytometry assays, respectively. Based on our results, knockdown of CRABP2 by shRNA resulted in the inhibition of tumor proliferation, migration, and invasion in vitro, followed by increased tumor apoptosis-related protein expression and decreased ERK/VEGF pathway-related proteins expression. CRABP2 silencing in HCC cells also resulted in the failure to develop tumors in vivo. These results provide important insights into the role of CRABP2 in the development and development of HCC. Based on our findings, CRABP2 may be used as a novel diagnostic biomarker, and regulation of CRABP2 in HCC may provide a potential molecular target for the therapy of HCC.
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Affiliation(s)
- Qingmin Chen
- Department of General Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, China
| | - Ludong Tan
- Department of General Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, China
| | - Zhe Jin
- Department of General Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, China
| | - Yahui Liu
- Department of General Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, China
| | - Ze Zhang
- Department of General Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, China
- Department of Hepatobiliary-Pancreatic Surgery, China-Japan Union Hospital of Jilin University, 126 Xiantai Street, Changchun, Jilin 130000, China
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Wang H, Yu H, Qian YW, Cao ZY, Wu MC, Cong WM. Impact of Surgical Margin on the Prognosis of Early Hepatocellular Carcinoma (≤5 cm): A Propensity Score Matching Analysis. Front Med (Lausanne) 2020; 7:139. [PMID: 32478080 PMCID: PMC7232563 DOI: 10.3389/fmed.2020.00139] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2019] [Accepted: 03/30/2020] [Indexed: 12/11/2022] Open
Abstract
Aim: The influence of surgical margin on the prognosis of patients with early solitary hepatocellular carcinoma (HCC) (≤5 cm) is undetermined. Methods: The data of 904 patients with early solitary HCC who underwent liver resection were collected for recurrence-free survival (RFS) and overall survival (OS). Propensity score matching (PSM) was performed to balance the potential bias. Results: Log-rank tests showed that 2 mm was the best cutoff value to discriminate the prognosis of early HCC. Liver resection with a >2 mm surgical margin distance (wide-margin group) led to better 5-year RFS and OS rate compared with liver resection with a ≤2 mm surgical margin distance (narrow-margin group) among patients both before (RFS: 59.1% vs. 39.6%, P < 0.001; OS: 85.3% vs. 73.7%, P < 0.001) and after PSM (RFS: 56.3% vs. 41.0%, P < 0.001; OS: 83.0% vs. 75.0%, P = 0.010). Subgroup analysis showed that a wide-margin resection significantly improved the prognosis of patients with microvascular invasion (RFS: P < 0.001; OS: P = 0.001) and patients without liver cirrhosis (RFS: P < 0.001; OS: P = 0.001) after PSM. Multivariable Cox regression analysis revealed that narrow-margin resection is associated with poorer RFS [hazard ratio (HR) = 1.781, P < 0.001), OS (HR = 1.935, P < 0.001], and early recurrence (HR = 1.925, P < 0.001). Conclusions: A wide-margin resection resulted in better clinical outcomes than a narrow-margin resection among patients with early solitary HCC, especially for those with microvascular invasion and without cirrhosis. An individual strategy of surgical margin should be formulated preoperation according to both tumor factors and background liver factors.
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Affiliation(s)
- Han Wang
- Department of Pathology, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
| | - Hua Yu
- Department of Pathology, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
| | - You-Wen Qian
- Department of Pathology, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
| | - Zhen-Ying Cao
- Department of Pathology, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
| | - Meng-Chao Wu
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
| | - Wen-Ming Cong
- Department of Pathology, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
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Xu L, Li L, Wang P, Zhang M, Zhang Y, Hao X, Yan L, Li B, Wen T, Xu M. Novel Prognostic Nomograms for Hepatocellular Carcinoma Patients with Microvascular Invasion: Experience from a Single Center. Gut Liver 2020; 13:669-682. [PMID: 30970430 PMCID: PMC6860039 DOI: 10.5009/gnl18489] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2018] [Revised: 12/26/2018] [Accepted: 12/28/2018] [Indexed: 02/05/2023] Open
Abstract
Background/Aims Microvascular invasion (MVI) is an established risk factor for hepatocellular carcinoma (HCC). However, prediction models that specifically focus on the individual prognoses of HCC patients with MVI is lacking. Methods A total of 385 HCC patients with MVI were randomly assigned to training and validation cohorts in a 2:1 ratio. The outcomes were disease-free survival (DFS) and overall survival (OS). Prognostic nomograms were established based on the results of multivariate analyses. The concordance index (C-index), calibration plots and Kaplan-Meier curves were employed to evaluate the accuracy, calibration and discriminatory ability of the models. Results The independent risk factors for both DFS and OS included age, tumor size, tumor number, the presence of gross vascular invasion, and the presence of Glisson’s capsule invasion. The platelet-to-lymphocyte ratio was another risk factor for OS. On the basis of these predictors, two nomograms for DFS and OS were constructed. The C-index values of the nomograms for DFS and OS were 0.712 (95% confidence interval [CI], 0.679 to 0.745; p<0.001) and 0.698 (95% CI, 0.657 to 0.739; p<0.001), respectively, in the training cohort and 0.704 (95% CI, 0.650 to 0.708; p<0.001) and 0.673 (95% CI, 0.607 to 0.739; p<0.001), respectively, in the validation cohort. The calibration curves showed optimal agreement between the predicted and observed survival rates. The Kaplan-Meier curves suggested that these two nomograms had satisfactory discriminatory abilities. Conclusions These novel predictive models have satisfactory accuracy and discriminatory abilities in predicting the prognosis of HCC patients with MVI after hepatectomy.
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Affiliation(s)
- Liangliang Xu
- Department of Liver Surgery, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Lian Li
- Department of Liver Surgery, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Peng Wang
- Department of Liver Surgery, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Ming Zhang
- Department of Liver Surgery, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Yanfang Zhang
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Xiangyong Hao
- Department of General Surgery, Gansu Provincial Hospital, Lanzhou, China
| | - Lvnan Yan
- Department of Liver Surgery, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Bo Li
- Department of Liver Surgery, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Tianfu Wen
- Department of Liver Surgery, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Mingqing Xu
- Department of Liver Surgery, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
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Wang S, Yang Y, Sun L, Qiao G, Song Y, Liu B. Exosomal MicroRNAs as Liquid Biopsy Biomarkers in Hepatocellular Carcinoma. Onco Targets Ther 2020; 13:2021-2030. [PMID: 32210570 PMCID: PMC7069575 DOI: 10.2147/ott.s232453] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2019] [Accepted: 02/04/2020] [Indexed: 12/21/2022] Open
Abstract
Purpose Hepatocellular carcinoma (HCC) has a high incidence in China and exploring effective ways for early diagnosis is an important method to improve the prognosis of patients with HCC. Additional studies reported that. Some kinds of microRNA (miRNA) in plasma will change accordingly during HCC progress, and this change can be used to diagnose HCC, especially with miRNA-122, miRNA-21 and miRNA-96. We were aiming at investigating the values of the exosomal miRNAs in diagnosis and prognosis for HCC patients. Patients and Methods Blood samples from 50 patients with HCC and 50 patients with hepatic cirrhosis and 50 healthy volunteers were obtained. The diagnostic accuracy of the plasma and exosomal miRNAs and the comparisons among different groups were measured by the area under the curve (AUC) on receiver operating characteristic (ROC) curve analysis. Results Expression levels of miRNA-21 and miRNA-96 were significantly higher in patients with HCC and of miRNA-122 were significantly lower in HCC compared with cirrhotic patients in both exosomes and plasma. Among different groups, exosomal miRNA-122, miRNA-21 and miRNA-96 were significantly more accurate in diagnosing HCC than those miRNAs in plasma and the alpha-fetoprotein (AFP) level. The miRNA panel had high accuracy in discriminating HCC from the cirrhosis group (AUC 0.924; 95% CI; sensitivity 82%, specificity 92%) and healthy volunteers’ group. Exosomal miRNA-21 and miRNA-96 with low expression and miRNA-122 with high expression could be associated with a patient’s survival time. However, the miRNA panel could better predict the HCC patient’s survival time compared with each miRNA individually. Conclusion This study showed that the expression levels of miRNA-122, miRNA-21 and miRNA-96 in exosomes were more significantly changed than those miRNAs in plasma in patients with HCC compared with cirrhotic patients, and the exosomal miRNA panel containing miRNA-122, miRNA-21 and miRNA-96 could be defined as a diagnostic biomarker for patients with HCC. We also conclude that different expression of exosomal miRNAs, especially the miRNA panel, could predict the HCC patient’s prognosis.
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Affiliation(s)
- Shuo Wang
- Department of Medical Oncology, Beijing Shijitan Hospital, Beijing, People's Republic of China
| | - Yongxiang Yang
- Outpatient Department, PLA Rocket Force Characteristic Medical Center, Beijing, People's Republic of China
| | - Lili Sun
- Department of Stomatology, Beijing Chuiyangliu Hospital, Beijing, People's Republic of China
| | - Guoliang Qiao
- Department of Medical Oncology, Beijing Shijitan Hospital, Beijing, People's Republic of China
| | - Yunlong Song
- Department of Pharmacy, PLA Rocket Force Characteristic Medical Center, Beijing, People's Republic of China
| | - Bing Liu
- Department of Disease Control and Prevention, PLA Rocket Force Characteristic Medical Center, Beijing, People's Republic of China
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Tang C, Zhao R, Ni H, Zhao K, He Y, Fang S, Chen Q. Molecule mechanisms of Ganoderma lucidum treated hepatocellular carcinoma based on the transcriptional profiles and miRNA-target network. Biomed Pharmacother 2020; 125:110028. [PMID: 32106374 DOI: 10.1016/j.biopha.2020.110028] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2020] [Revised: 02/13/2020] [Accepted: 02/17/2020] [Indexed: 12/19/2022] Open
Abstract
Ganoderma lucidum has salutary effects on tumor treatment, including pancreatic cancer and hepatocellular carcinoma. However, the molecular mechanisms underlying Ganoderma lucidum therapy is obscure. In this study, the Hepa1-6-bearing C57 BL/6 mouse model was utilized to explore the therapeutic efficacy of Ganoderma lucidum extract (GLE), documenting that it could effectively inhibit tumor growth. The microRNA (miRNA) profiles of GLE-treated and untreated mice were detected, and 25 differentially expressed (DE) miRNAs were determined, including 24 up-expressed and one down-expressed miRNAs. Using the ClusterOne algorithm, 8 hub miRNAs were isolated from the established miRNA-target network. The qRT-PCR assay demonstrated that these 8 miRNAs were up-expressed in the GLE treated tumor mice. Furthermore, the mRNA profiles showed that there are 76 DE mRNAs between GLE treated and model groups. The protein-protein interaction (PPI) network shows that Cntn1, Irs1, Nfkbia, Rybp and Ywhaz playing important roles, and qRT-PCR further revealed they were down-expressed in GLE treated Hepa1-6-bearing C57 BL/6 mice. The rebuilt miRNA-target network was shown that these 5 mRNAs were regulated by mmu-mir-23a-5p, -3102-3p, -337-3p, and -467a-3p, respectively. This study suggested that these 4 interesting miRNAs were potential biomarkers for evaluation of GLE efficacy, which may down-regulate the expression of Cntn1, Irs1, Nfkbia, Rybp and Ywhaz, and mediate many signaling pathways occurring in tumor treatment.
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Affiliation(s)
- Chenchen Tang
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Ruolin Zhao
- Department of Basic Medicine, Naval Medical University, Shanghai 200433, China
| | - Hongmei Ni
- School of Basic Medicine College, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Kunpeng Zhao
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - YuMin He
- School of Basic Medicine College, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Shengquan Fang
- Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China.
| | - Qilong Chen
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
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Wan S, Nie Y, Zhu X. Development of a prognostic scoring model for predicting the survival of elderly patients with hepatocellular carcinoma. PeerJ 2020; 8:e8497. [PMID: 32117619 PMCID: PMC7006515 DOI: 10.7717/peerj.8497] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2019] [Accepted: 12/31/2019] [Indexed: 12/19/2022] Open
Abstract
Background The number of elderly hepatocellular carcinoma (HCC) patients is increasing, and precisely assessing of the prognosis of these patients is necessary. We developed a prognostic scoring model to predict survival in elderly HCC patients. Methods We extracted data from 4,076 patients ≥65 years old from the Surveillance, Epidemiology, and End Results (SEER) database and randomly divided them into training and validation groups. Cox regression analysis was used to screen for meaningful independent prognostic factors. The receiver operating characteristic curve reflected the model's discrimination power. Results Age, race, American Joint Committee on Cancer stage, degree of tumour differentiation, tumour size, alpha-fetoprotein and tumour therapy were independent prognostic factors for survival in elderly HCC patients. We developed a prognostic scoring model based on the seven meaningful variables to predict survival in elderly HCC patients. The AUCs of the model were 0.805 (95% CI [0.788-0.821]) and 0.788 (95% CI [0.759-0.816]) in the training and validation groups, respectively. We divided the patients into low-risk groups and high-risk groups according to the optimal cut-off value. The Kaplan-Meier survival curve showed that in the training and validation groups, the survival rate of the low-risk group was significantly higher than that of the high-risk group (P < 0.001). Conclusion Based on a large population, we constructed a prognostic scoring model for predicting survival in elderly HCC patients. The model may provide a reference for clinicians for preoperative and postoperative evaluations of elderly HCC patients.
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Affiliation(s)
- Sizhe Wan
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Yuan Nie
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Xuan Zhu
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China
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Zhang L, Kuang S, Chen J, Zhang Y, Zhao B, Peng H, Xiao Y, Fowler K, Wang J, Sirlin CB. The Role of Preoperative Dynamic Contrast-enhanced 3.0-T MR Imaging in Predicting Early Recurrence in Patients With Early-Stage Hepatocellular Carcinomas After Curative Resection. Front Oncol 2019; 9:1336. [PMID: 31850221 PMCID: PMC6892896 DOI: 10.3389/fonc.2019.01336] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2019] [Accepted: 11/15/2019] [Indexed: 12/12/2022] Open
Abstract
Objectives: Liver resection is potentially curative for early-stage hepatocellular carcinoma (eHCC) in patients with well-preserved liver function. The prognosis of these patients after resection is still unsatisfactory because of frequent early recurrence (ER). Therefore, we investigated the role of preoperative dynamic contrast-enhanced 3.0-T MR imaging in predicting ER of eHCC after curative resection. Methods From May 2014 to October 2017, we retrospectively analyzed 82 patients with eHCC who underwent dynamic MR imaging and subsequently underwent curative resection. Liver Imaging Reporting and Data System (LI-RADS) v2018 major and ancillary imaging features, as well as two non-LI-RADS MR imaging features (irregular tumor margin and tumor number), were evaluated. A multivariate Cox regression analysis was used to identify independent predictors, and two models (preoperative and postoperative prediction models) were developed. Results ER was observed in 25 patients (25/82, 30.5%). In the univariate analyses, preoperative alpha-fetoprotein (AFP) level >200 ng/ml, three MR imaging features (multifocal tumors, corona enhancement, and irregular tumor margin), and microvascular invasion (MVI) were associated with ER. In the multivariate analysis, corona enhancement (hazard ratio [HR]: 2.970; p = 0.013) and irregular tumor margin (HR: 2.377; p = 0.048) were independent predictors in the preoperative prediction model, and preoperative AFP level >200 ng/ml (HR: 2.493; p = 0.044) plus corona enhancement (HR: 3.046; p = 0.014) were independent predictors in the postoperative prediction model (microvascular invasion [MVI] was not; p = 0.061). When combined with both predictors, the specificity for ER in the preoperative prediction model was 98.2% (56/57), which was comparable to that of the postoperative prediction model [96.7% (55/57)]. Conclusions Our results demonstrated that preoperative MR imaging features (corona enhancement and irregular tumor margin) have the potential to preoperatively identify high-risk ER patients with eHCC, with a specificity >90%.
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Affiliation(s)
- Linqi Zhang
- Department of Radiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Sichi Kuang
- Department of Radiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Jingbiao Chen
- Department of Radiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yao Zhang
- Department of Radiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Binliang Zhao
- Department of Radiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Hao Peng
- Department of Nuclear Medicine, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China
| | - Yuanqiang Xiao
- Department of Radiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Kathryn Fowler
- Liver Imaging Group, Department of Radiology, University of California, San Diego, La Jolla, CA, United States
| | - Jin Wang
- Department of Radiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Claude B Sirlin
- Liver Imaging Group, Department of Radiology, University of California, San Diego, La Jolla, CA, United States
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Wei F, Liu H, Liang X, Yu T. Population‐level utilization of anatomic resection in early hepatocellular carcinoma (≤5 cm): post‐operative, middle‐ and long‐term outcomes. ANZ J Surg 2019; 90:547-552. [PMID: 31770828 DOI: 10.1111/ans.15567] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2019] [Revised: 10/07/2019] [Accepted: 10/09/2019] [Indexed: 12/11/2022]
Affiliation(s)
- Fangqiang Wei
- Department of Hepatobiliary and Pancreatic SurgeryZhejiang Provincial People's Hospital, Hangzhou Medical College Hangzhou China
| | - Hui Liu
- Zhejiang Provincial Key Laboratory of Laparoscopic TechnologySir Run Run Shaw Hospital, School of Medicine, Zhejiang University Hangzhou China
| | - Xiao Liang
- Department of General SurgerySir Run Run Shaw Hospital, School of Medicine, Zhejiang University Hangzhou China
| | - Tunan Yu
- Department of General SurgerySir Run Run Shaw Hospital, School of Medicine, Zhejiang University Hangzhou China
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Lu W, Tang H, Yang Z, Jiang K, Chen Y, Lu S. Clinical predictors of small solitary hepatitis B virus-related hepatocellular carcinoma microinvasion. ANZ J Surg 2019; 89:E438-E442. [PMID: 31508888 DOI: 10.1111/ans.15403] [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: 06/01/2019] [Revised: 07/17/2019] [Accepted: 07/18/2019] [Indexed: 11/29/2022]
Abstract
BACKGROUND Microinvasion serves as a reliable indicator of poor prognosis after hepatectomy or transplantation for hepatocellular carcinoma (HCC). However, microinvasion is difficult to detect with current imaging modalities and is usually diagnosed histopathologically. The aim of this study is to identify the preoperative clinical predictors of microinvasion of small solitary hepatitis B virus (HBV)-related HCC. METHODS From January 2000 to December 2009, 110 patients with HBV-related small primary solitary HCC (tumour diameter ≤3.0 cm) who underwent hepatectomy at Chinese PLA General Hospital were enrolled. The independent predictors of microinvasion, such as microvascular invasion and microscopic satellite nodules, were analysed. The prognosis of patients with microinvasion was compared with that of patients without microinvasion. RESULTS Of the 110 patients, 31 (28.2%) exhibited microinvasion. Among them, 16 (51.6%) had microvascular invasion with microscopic satellite nodules, five (16.1%) had microscopic satellite nodules without microvascular invasion and 10 (32.3%) had microvascular invasion without microscopic satellite nodules. Two independent predictors of microinvasion were identified: serum alpha-fetoprotein >20 ng/mL and a viral load of >104 copies/mL. Patients without microinvasion exhibited a significantly better prognostic outcome compared with those with microinvasion. CONCLUSION Regarding HBV-related small HCC, patients presenting with alpha-fetoprotein levels >20 ng/mL and a high viral load (HBV-DNA >104 copies/mL) are at substantial risk for microinvasion.
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Affiliation(s)
- Wenping Lu
- Department of Hepatobiliary Surgery, First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Haowen Tang
- Department of Hepatobiliary Surgery, First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Zhanyu Yang
- Department of Hepatobiliary Surgery, First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Kai Jiang
- Department of Hepatobiliary Surgery, First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Yongliang Chen
- Department of Hepatobiliary Surgery, First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Shichun Lu
- Department of Hepatobiliary Surgery, First Medical Center of Chinese PLA General Hospital, Beijing, China
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