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Huang R, Cui J. Impact of Linggui Zhugan decoction on microwave ablation outcomes and recurrence in liver cancer. World J Gastrointest Oncol 2025; 17:101177. [PMID: 39958537 PMCID: PMC11756010 DOI: 10.4251/wjgo.v17.i2.101177] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Revised: 11/05/2024] [Accepted: 12/02/2024] [Indexed: 01/18/2025] Open
Abstract
BACKGROUND Liver cancer is one of the most common malignant tumors of the digestive system, and early detection and effective treatment are crucial for improving the prognosis. Microwave ablation (MWA) has shown promising results as a local therapeutic method for liver cancer; however, further improvement of its efficacy remains a key focus of current research. AIM To evaluate the clinical efficacy of Linggui Zhugan decoction combined with MWA for the treatment of primary liver cancer. METHODS Data were collected from 164 patients with primary liver cancer who underwent MWA at our hospital between March 2019 and April 2021. Among them, 79 patients (control group) received routine treatments and 85 patients (research group) received Linggui Zhugan decoction in addition to routine treatment. The clinical efficacy, incidence of adverse reactions, and levels of serum alpha-fetoprotein (AFP), des-γ-carboxy prothrombin (DCP), AFP-L3, total bilirubin (TBil), alanine aminotransferase (ALT), CD4 cell count, CD8 cell count, and CD4/CD8 ratio were compared between the two groups, before and after treatment. The three-year recurrence rates between the two groups were compared, and independent prognostic factors for recurrence were identified. RESULTS The study results revealed that the objective response rate (ORR) in the research group was significantly higher than that in the control group (P = 0.005). After treatment, the CD4 cell count and CD4/CD8 ratio significantly increased, whereas the CD8 cell count and TBil, ALT, AFP, DCP, and AFP-L3 Levels were significantly lower in the research group than in the control group (P < 0.001). The Cox regression analysis revealed that the treatment regimen (P = 0.003), presence of cirrhosis (P = 0.019), tumor diameter (P = 0.037), Child-Pugh score (P = 0.003), pretreatment AFP level (P = 0.006), and AFP-L3 Level (P = 0.002) were independent prognostic factors for disease-free survival. CONCLUSION The combination of Linggui Zhugan decoction with MWA significantly improved the clinical efficacy and long-term prognosis of patients with primary liver cancer.
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Affiliation(s)
- Rui Huang
- Department of Acupuncture and Moxibustion, Baoji Central Hospital, Baoji 721000, Shaanxi Province, China
| | - Jing Cui
- Department of Liver Disease, Xi’an Daxing Hospital, Xi’an 710016, Shaanxi Province, China
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Xie H, Shi B, Fan J, Liu S, Ma Q, Dai J, Dong S, Liu Y, Meng H, Liu H, Yang Y, Mu X. A predictive model based on radiomics, clinical features, and pathologic indicators for disease-free survival after liver transplantation for hepatocellular carcinoma: a 7-year retrospective study. J Gastrointest Oncol 2024; 15:2187-2200. [PMID: 39554565 PMCID: PMC11565123 DOI: 10.21037/jgo-24-347] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2024] [Accepted: 09/04/2024] [Indexed: 11/19/2024] Open
Abstract
Background Disease-free survival (DFS) is an essential indicator for evaluating the prognosis of liver transplantation (LT) in hepatocellular carcinoma (HCC) patients. Despite progress in the prediction of DFS by radiomics, only preoperative clinical features have been combined in most studies. The aim of this study was to construct a nomogram model (NM) using preoperative clinical features, radiomics, and postoperative pathological indicators for more effective prediction of DFS. Methods This was a retrospective study of a single-center cohort comprising 139 HCC patients. Using the whole cohort, we constructed and assessed a clinical model (CM) based on alpha-fetoprotein (AFP) and alkaline phosphatase (ALP), a pathological model (PM) based on Ki-67 and tumor number, a radiomics model (RM) based on the radiomics score (Rad-score), and an NM based on the above five independent predictors. Results Significant correlations between the NM and DFS were observed in the training and validation cohorts. Among the four prediction models, the C-index of the NM was the highest [(training/validation cohort) CM: 0.664/0.676, PM: 0.737/0.691, RM: 0.706/0.697, NM: 0.817/0.760], and the areas under the receiver operating characteristic curves (AUCs) of the NM prediction of 1-year, 2-year, and 3-year DFS were also the highest [(training/validation cohort) 1-year, 2-year, and 3-year CM: 0.726/0.726, 0.685/0.744, 0.645/0.686, PM: 0.789/0.780, 0.801/0.748, 0.841/0.735, RM: 0.769/0.752, 0.717/0.805, 0.748/0.765, NM: 0.882/0.854, 0.867/0.849, 0.882/0.801]. The NM also exhibited the highest net clinical benefit. Conclusions Based on radiomics, clinical features, and pathological indicators, the NM could be used to effectively predict DFS after LT in HCC patients, guiding the follow-up and complementary treatment.
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Affiliation(s)
- Hao Xie
- Postgraduate Training Base of the Third Medical Center of Chinese PLA General Hospital, Jinzhou Medical University, Beijing, China
- Department of Radiology, the Jintang First People’s Hospital, Chengdu, China
| | - Bin Shi
- Department of Organ Transplantation, the Third Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Junzhen Fan
- Department of Pathology, the Third Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Shui Liu
- Department of Radiology, Aerospace Center Hospital, Beijing, China
| | - Qiaozhi Ma
- Department of Radiology, the Third Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Junnan Dai
- Department of Radiology, the Third Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Siqing Dong
- Department of Radiation Oncology, Jinzhou Central Hospital, Jinzhou, China
| | - Ying Liu
- School of Medical Imaging, Weifang Medical University, Weifang, China
| | - Han Meng
- Postgraduate Training Base of the Third Medical Center of Chinese PLA General Hospital, Jinzhou Medical University, Beijing, China
| | - Hui Liu
- Department of Radiology, the Jintang First People’s Hospital, Chengdu, China
| | - Ya Yang
- Department of Ultrasound Medicine, the Jintang First People’s Hospital, Chengdu, China
| | - Xuetao Mu
- Department of Radiology, the Third Medical Center of Chinese PLA General Hospital, Beijing, China
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Wehrle CJ, Hong H, Kamath S, Schlegel A, Fujiki M, Hashimoto K, Kwon DCH, Miller C, Walsh RM, Aucejo F. Tumor Mutational Burden From Circulating Tumor DNA Predicts Recurrence of Hepatocellular Carcinoma After Resection: An Emerging Biomarker for Surveillance. Ann Surg 2024; 280:504-513. [PMID: 38860385 DOI: 10.1097/sla.0000000000006386] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/12/2024]
Abstract
OBJECTIVE Describe the utility of circulating tumor DNA in the postoperative surveillance of hepatocellular carcinoma (HCC). BACKGROUND Current biomarkers for HCC like alpha-fetoprotein (AFP) are lacking. Circulating tumor DNA (ctDNA) has shown promise in colorectal and lung cancers, but its utility in HCC remains relatively unknown. METHODS Patients with HCC undergoing curative-intent resection from November 1, 2020, to July 1, 2023, received ctDNA testing using the Guardant360 platform. Tumor mutational burden (TMB) is calculated as the number of somatic mutations-per-megabase of genomic material identified. RESULTS Forty-seven patients had postoperative ctDNA testing. The mean follow-up was 27 months, and the maximum was 43.2 months. Twelve patients (26%) experienced recurrence. Most (n=41/47, 87.2%) had identifiable ctDNA postoperatively; 55.3% (n=26) were TMB-not detected versus 45.7% (n=21) TMB-detectable. Postoperative identifiable ctDNA was not associated with RFS ( P =0.518). Detectable TMB was associated with reduced RFS (6.9 vs 14.7 mo, P =0.049). There was a higher rate of recurrence in patients with TMB (n=9/21, 42.9%, vs n=3/26, 11.5%, P =0.02). Area under the curve for TMB-prediction of recurrence was 0.752 versus 0.550 for AFP. ROC analysis established a TMB cutoff of 4.8mut/mB for predicting post-operative recurrence ( P =0.002) and RFS ( P =0.025). AFP was not correlated with RFS using the lab-normal cutoff (<11 ng/mL, P =0.682) or the cutoff established by ROC analysis (≥4.6 ng/mL, P =0.494). TMB-high was associated with poorer RFS on cox-regression analysis (hazard ratio=5.386, 95% CI: 1.109-26.160, P =0.037), while microvascular invasion ( P =0.853) and AFP ( P =0.439) were not. CONCLUSIONS Identifiable TMB on postoperative ctDNA predicts HCC recurrence and outperformed AFP in this cohort. Perioperative ctDNA may be a useful surveillance tool following curative-intent hepatectomy. Larger-scale studies are needed to confirm this utility and investigate additional applications in HCC patients, including the potential for prophylactic treatment in patients with residual TMB after resection.
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Affiliation(s)
- Chase J Wehrle
- Department of Hepato-pancreato-biliary & Liver Transplant Surgery, Cleveland Clinic Foundation, Digestive Diseases and Surgery Institute, Cleveland
| | - Hanna Hong
- Department of Hepato-pancreato-biliary & Liver Transplant Surgery, Cleveland Clinic Foundation, Digestive Diseases and Surgery Institute, Cleveland
| | - Suneel Kamath
- Department of Hematology and Oncology, Cleveland Clinic Foundation, Taussig Cancer Institute, Cleveland, OH
| | - Andrea Schlegel
- Department of Hepato-pancreato-biliary & Liver Transplant Surgery, Cleveland Clinic Foundation, Digestive Diseases and Surgery Institute, Cleveland
| | - Masato Fujiki
- Department of Hepato-pancreato-biliary & Liver Transplant Surgery, Cleveland Clinic Foundation, Digestive Diseases and Surgery Institute, Cleveland
| | - Koji Hashimoto
- Department of Hepato-pancreato-biliary & Liver Transplant Surgery, Cleveland Clinic Foundation, Digestive Diseases and Surgery Institute, Cleveland
| | - David Choon Hyuck Kwon
- Department of Hepato-pancreato-biliary & Liver Transplant Surgery, Cleveland Clinic Foundation, Digestive Diseases and Surgery Institute, Cleveland
| | - Charles Miller
- Department of Hepato-pancreato-biliary & Liver Transplant Surgery, Cleveland Clinic Foundation, Digestive Diseases and Surgery Institute, Cleveland
| | - R Matthew Walsh
- Department of Hepato-pancreato-biliary & Liver Transplant Surgery, Cleveland Clinic Foundation, Digestive Diseases and Surgery Institute, Cleveland
| | - Federico Aucejo
- Department of Hepato-pancreato-biliary & Liver Transplant Surgery, Cleveland Clinic Foundation, Digestive Diseases and Surgery Institute, Cleveland
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He L, Ji WS, Jin HL, Lu WJ, Zhang YY, Wang HG, Liu YY, Qiu S, Xu M, Lei ZP, Zheng Q, Yang XL, Zhang Q. Development of a nomogram for predicting liver transplantation prognosis in hepatocellular carcinoma. World J Gastroenterol 2024; 30:2763-2776. [PMID: 38899335 PMCID: PMC11185292 DOI: 10.3748/wjg.v30.i21.2763] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2024] [Revised: 04/24/2024] [Accepted: 05/13/2024] [Indexed: 06/03/2024] Open
Abstract
BACKGROUND At present, liver transplantation (LT) is one of the best treatments for hepatocellular carcinoma (HCC). Accurately predicting the survival status after LT can significantly improve the survival rate after LT, and ensure the best way to make rational use of liver organs. AIM To develop a model for predicting prognosis after LT in patients with HCC. METHODS Clinical data and follow-up information of 160 patients with HCC who underwent LT were collected and evaluated. The expression levels of alpha-fetoprotein (AFP), des-gamma-carboxy prothrombin, Golgi protein 73, cytokeratin-18 epitopes M30 and M65 were measured using a fully automated chemiluminescence analyzer. The best cutoff value of biomarkers was determined using the Youden index. Cox regression analysis was used to identify the independent risk factors. A forest model was constructed using the random forest method. We evaluated the accuracy of the nomogram using the area under the curve, using the calibration curve to assess consistency. A decision curve analysis (DCA) was used to evaluate the clinical utility of the nomograms. RESULTS The total tumor diameter (TTD), vascular invasion (VI), AFP, and cytokeratin-18 epitopes M30 (CK18-M30) were identified as important risk factors for outcome after LT. The nomogram had a higher predictive accuracy than the Milan, University of California, San Francisco, and Hangzhou criteria. The calibration curve analyses indicated a good fit. The survival and recurrence-free survival (RFS) of high-risk groups were significantly lower than those of low- and middle-risk groups (P < 0.001). The DCA shows that the model has better clinical practicability. CONCLUSION The study developed a predictive nomogram based on TTD, VI, AFP, and CK18-M30 that could accurately predict overall survival and RFS after LT. It can screen for patients with better postoperative prognosis, and improve long-term survival for LT patients.
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Affiliation(s)
- Li He
- Department of Organ Transplantation, The Third Medical Centre of Chinese PLA General Hospital, Beijing 100039, China
- School of Clinical Medicine, Shandong Second Medical University, Weifang 261053, Shandong Province, China
| | - Wan-Sheng Ji
- Clinical Research Center, The Affiliated Hospital of Shandong Second Medical University, Weifang 261053, Shandong Province, China
| | - Hai-Long Jin
- Department of Organ Transplantation, The Third Medical Centre of Chinese PLA General Hospital, Beijing 100039, China
| | - Wen-Jing Lu
- Department of Laboratory Medicine, The Third Medical Centre of Chinese PLA General Hospital, Beijing 100039, China
| | - Yuan-Yuan Zhang
- Department of Laboratory Medicine, The Third Medical Centre of Chinese PLA General Hospital, Beijing 100039, China
| | - Hua-Guang Wang
- Physiatry Department, Naval Aviation University, Yantai 100071, Shandong Province, China
| | - Yu-Yu Liu
- Department of Organ Transplantation, The Third Medical Centre of Chinese PLA General Hospital, Beijing 100039, China
| | - Shuang Qiu
- Department of Organ Transplantation, The Third Medical Centre of Chinese PLA General Hospital, Beijing 100039, China
| | - Meng Xu
- Department of Organ Transplantation, The Third Medical Centre of Chinese PLA General Hospital, Beijing 100039, China
| | - Zi-Peng Lei
- Department of Organ Transplantation, The Third Medical Centre of Chinese PLA General Hospital, Beijing 100039, China
| | - Qian Zheng
- Department of Organ Transplantation, The Third Medical Centre of Chinese PLA General Hospital, Beijing 100039, China
| | - Xiao-Li Yang
- Department of Laboratory Medicine, The Third Medical Centre of Chinese PLA General Hospital, Beijing 100039, China
| | - Qing Zhang
- Department of Organ Transplantation, The Third Medical Centre of Chinese PLA General Hospital, Beijing 100039, China
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Li W, Zhao B, Wang Q, Lu J, Wu X, Chen X. Integrated analysis of tumour-derived exosome-related immune genes to predict progression and immune status of hepatocellular carcinoma. Clin Immunol 2023; 256:109774. [PMID: 37774907 DOI: 10.1016/j.clim.2023.109774] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Revised: 09/01/2023] [Accepted: 09/12/2023] [Indexed: 10/01/2023]
Abstract
Tumour-derived exosomes (TDEs) play an important role in tumourigenesis and progression by regulating components in the tumour microenvironment (TME), however, the role of TDE-related immune genes in hepatocellular carcinoma is not fully known. We systematically analysed TDE genes from ExoCarta and immune genes from Immport,Machine learning ultimately identified eight TDE-related prognostic immune genes and used them as the basis for constructing a risk model, which was constructed to better predict patients with hepatocellular carcinoma (HCC) compared with published prognostic models. There were significant differences between the high and low risk groups in terms of biological functioning. Low-risk group were more sensitive to immunotherapy, the sensitivity to oxaliplatin and cisplatin differed between the high- and low-risk groups, and knockout of the core gene RAC1 limited the malignant biological behaviour of hepatocellular carcinoma cells. In conclusion, TIRGs are effective in predicting the prognosis of patients with hepatocellular carcinoma and provide a new perspective on immunotherapy and chemotherapy for patients.
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Affiliation(s)
- Wenhua Li
- Shihezi University School of Medicine, Shihezi 832000, China; Key Laboratory for Prevention and Treatment of High Morbidity in Central Asia, National Health and Health Commission, Shihezi 832000, China
| | - Bin Zhao
- Shihezi University School of Medicine, Shihezi 832000, China; Key Laboratory for Prevention and Treatment of High Morbidity in Central Asia, National Health and Health Commission, Shihezi 832000, China
| | - Qianwen Wang
- Shihezi University School of Medicine, Shihezi 832000, China; Key Laboratory for Prevention and Treatment of High Morbidity in Central Asia, National Health and Health Commission, Shihezi 832000, China
| | - Junxia Lu
- Shihezi University School of Medicine, Shihezi 832000, China; Key Laboratory for Prevention and Treatment of High Morbidity in Central Asia, National Health and Health Commission, Shihezi 832000, China
| | - Xiangwei Wu
- Shihezi University School of Medicine, Shihezi 832000, China; The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi 832000, China; Key Laboratory for Prevention and Treatment of High Morbidity in Central Asia, National Health and Health Commission, Shihezi 832000, China.
| | - Xueling Chen
- Shihezi University School of Medicine, Shihezi 832000, China; Key Laboratory for Prevention and Treatment of High Morbidity in Central Asia, National Health and Health Commission, Shihezi 832000, China.
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Chen Y, Yin S, Liu R, Yang Y, Wu Q, Lin W, Li W. β-Sitosterol activates autophagy to inhibit the development of hepatocellular carcinoma by regulating the complement C5a receptor 1/alpha fetoprotein axis. Eur J Pharmacol 2023; 957:175983. [PMID: 37598926 DOI: 10.1016/j.ejphar.2023.175983] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2023] [Revised: 07/25/2023] [Accepted: 08/09/2023] [Indexed: 08/22/2023]
Abstract
Hepatocellular carcinoma (HCC) is highly refractory. β-Sitosterol has been reported to suppress proliferation and migration as well as interfere with cell metabolism in tumors. However, there is limited information on the effects of β-sitosterol on HCC. Herein, we used a xenograft mouse model to investigate the effects of β-sitosterol on HCC tumor growth. The molecular mechanism was elucidated using quantitative real-time PCR, western blotting, lentiviral transfection, CCK8, scratch, Transwell, and Ad-mCherry-GFP-LC3B assays. The results showed that HepG2 cells highly expressed complement C5a receptor 1. β-Sitosterol antagonized complement component 5a and exerted inhibitory effects on the proliferation and migration of HepG2 cells. The inhibitory effect of β-sitosterol was reversed by the knockdown of complement C5a receptor 1. Bioinformatics analysis suggested alpha fetoprotein (AFP) as a downstream factor of complement C5a receptor 1. β-Sitosterol inhibited AFP expression, which was reversed by complement C5a receptor 1 knockdown. The inhibitory effects of β-sitosterol on cell proliferation and migration were weakened by AFP overexpression. Furthermore, β-sitosterol induced autophagy in HepG2 cells, which was reversed by complement C5a receptor 1 knockdown and AFP overexpression. Blockade of autophagy by 3-MA attenuated β-sitosterol inhibition of proliferation and migration in HepG2 cells. Moreover, β-sitosterol inhibited HCC progression in vivo. Our findings demonstrate that β-sitosterol inhibits HCC advancement by activating autophagy through the complement C5a receptor 1/AFP axis. These findings recommend β-sitosterol as a promising therapy for HCC.
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Affiliation(s)
- Yuankun Chen
- Department of Infectious and Tropical Diseases, The Second Affiliated Hospital of Hainan Medical University, Hainan, Haikou 570100, China; Key Laboratory of Tropical Translational Medicine of Ministry of Health, Hainan Medical University, Hainan, Haikou 571199, China
| | - Song Yin
- Department of Infectious Disease, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Anhui, Hefei 230001, China; Wannan Medical College, Anhui, Wuhu 241002, China
| | - Rui Liu
- Department of Infectious and Tropical Diseases, The Second Affiliated Hospital of Hainan Medical University, Hainan, Haikou 570100, China; Key Laboratory of Tropical Translational Medicine of Ministry of Health, Hainan Medical University, Hainan, Haikou 571199, China
| | - Yijun Yang
- Department of Infectious and Tropical Diseases, The Second Affiliated Hospital of Hainan Medical University, Hainan, Haikou 570100, China; Key Laboratory of Tropical Translational Medicine of Ministry of Health, Hainan Medical University, Hainan, Haikou 571199, China
| | - Qiuping Wu
- Department of Infectious and Tropical Diseases, The Second Affiliated Hospital of Hainan Medical University, Hainan, Haikou 570100, China; Key Laboratory of Tropical Translational Medicine of Ministry of Health, Hainan Medical University, Hainan, Haikou 571199, China
| | - Wenyu Lin
- Liver Center and Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
| | - Wenting Li
- Department of Infectious and Tropical Diseases, The Second Affiliated Hospital of Hainan Medical University, Hainan, Haikou 570100, China; Key Laboratory of Tropical Translational Medicine of Ministry of Health, Hainan Medical University, Hainan, Haikou 571199, China; Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Anhui, Hefei 230022, China.
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Sönmez RE, Besson FL, Ghidaglia J, Lewin M, Gomez L, Salloum C, Pittau G, Ciacio O, Allard MA, Cherqui D, Adam R, Sa Cunha A, Azoulay D, Vibert E, Golse N. Towards refining the utility of dual (18F-FDG / 18F-Choline) PET/CT for the management of hepatocellular carcinoma: a tertiary center study. THE QUARTERLY JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING : OFFICIAL PUBLICATION OF THE ITALIAN ASSOCIATION OF NUCLEAR MEDICINE (AIMN) [AND] THE INTERNATIONAL ASSOCIATION OF RADIOPHARMACOLOGY (IAR), [AND] SECTION OF THE SOCIETY OF... 2023; 67:206-214. [PMID: 36345856 DOI: 10.23736/s1824-4785.22.03485-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Abstract
BACKGROUND The role of positron emission tomography/computed tomography (PET/CT) in hepatocellular carcinoma (HCC) management is not clearly defined. Our objective was to analyze the utility of dual-PET/CT (18F-FDG + 18F-Choline) imaging findings on the BCLC staging and treatment decision for HCC patients. METHODS Between January 2011 and April 2019, 168 consecutive HCC patients with available baseline dual-PET/CT imaging data were retrospectively analyzed. To identify potential refinement criteria for surgically-treated patients, survival Kaplan-Meier curves of various standard-of-care and dual-PET/CT baseline parameters were estimated. Finally, multivariate cox proportional hazard ratios of the most relevant clinico-biological and/or PET parameters were estimated. RESULTS Dual-PET/CT findings increased the score of BCLC staging in 21 (12.5%) cases. In 24.4% (N.=41) of patients, the treatment strategy was modified by the PET findings. Combining AFP levels at a threshold of 10 ng/mL with 18F-FDG or 18F-Choline N status significantly impacted DFS (P<0.05). In particular, the combined criteria of the N+ status assessed by 18F-Choline with AFP threshold of 10 ng/mL provided a highly predictive composite parameter for estimation of DFS according to multivariate analysis (HR=10.6, P<0.05). CONCLUSIONS The 18F-Choline / AFP composite parameter appears promising, and further prospective studies are mandatory to validate its oncological impact.
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Affiliation(s)
- Recep Erçin Sönmez
- Department of Hepatobiliary Surgery, Hepato-Biliary Center, Paul-Brousse Hospital, Assistance Publique Hôpitaux de Paris, Villejuif, France -
| | - Florent L Besson
- Department of Biophysics and Nuclear Medicine-Molecular Imaging, Paris-Saclay University Hospital, Assistance Publique-Hôpitaux de Paris, Le Kremlin-Bicêtre, France
- Paris-Saclay University, CEA, CNRS, Inserm, BioMaps, Orsay, France
- School of Medicine, Paris-Saclay Univrsity, Le Kremlin-Bicêtre, France
| | - Jerome Ghidaglia
- Department of Biophysics and Nuclear Medicine-Molecular Imaging, Paris-Saclay University Hospital, Assistance Publique-Hôpitaux de Paris, Le Kremlin-Bicêtre, France
| | - Maïté Lewin
- Department of Radiology, Paul-Brousse Hospital, Assistance Publique Hôpitaux de Paris, Centre Hépato-Biliaire, Villejuif, France
| | - Lea Gomez
- Department of Biophysics and Nuclear Medicine-Molecular Imaging, Paris-Saclay University Hospital, Assistance Publique-Hôpitaux de Paris, Le Kremlin-Bicêtre, France
| | - Chady Salloum
- Department of Hepatobiliary Surgery, Hepato-Biliary Center, Paul-Brousse Hospital, Assistance Publique Hôpitaux de Paris, Villejuif, France
| | - Gabriella Pittau
- Department of Hepatobiliary Surgery, Hepato-Biliary Center, Paul-Brousse Hospital, Assistance Publique Hôpitaux de Paris, Villejuif, France
| | - Oriana Ciacio
- Department of Hepatobiliary Surgery, Hepato-Biliary Center, Paul-Brousse Hospital, Assistance Publique Hôpitaux de Paris, Villejuif, France
| | - Marc Antoine Allard
- Department of Hepatobiliary Surgery, Hepato-Biliary Center, Paul-Brousse Hospital, Assistance Publique Hôpitaux de Paris, Villejuif, France
- Department of Pathogenesis and Treatment of Liver Diseases, Paris-Saclay University, INSERM, UMR-S 1193, Paris, France
| | - Daniel Cherqui
- Department of Hepatobiliary Surgery, Hepato-Biliary Center, Paul-Brousse Hospital, Assistance Publique Hôpitaux de Paris, Villejuif, France
- Department of Pathogenesis and Treatment of Liver Diseases, Paris-Saclay University, INSERM, UMR-S 1193, Paris, France
| | - René Adam
- Department of Hepatobiliary Surgery, Hepato-Biliary Center, Paul-Brousse Hospital, Assistance Publique Hôpitaux de Paris, Villejuif, France
- Research Group Chronotherapy, Cancers and Transplantation, Paris-Saclay University, Paris, France
| | - Antonio Sa Cunha
- Department of Hepatobiliary Surgery, Hepato-Biliary Center, Paul-Brousse Hospital, Assistance Publique Hôpitaux de Paris, Villejuif, France
- Department of Pathogenesis and Treatment of Liver Diseases, Paris-Saclay University, INSERM, UMR-S 1193, Paris, France
| | - Daniel Azoulay
- Department of Hepatobiliary Surgery, Hepato-Biliary Center, Paul-Brousse Hospital, Assistance Publique Hôpitaux de Paris, Villejuif, France
| | - Eric Vibert
- Department of Hepatobiliary Surgery, Hepato-Biliary Center, Paul-Brousse Hospital, Assistance Publique Hôpitaux de Paris, Villejuif, France
- Department of Pathogenesis and Treatment of Liver Diseases, Paris-Saclay University, INSERM, UMR-S 1193, Paris, France
| | - Nicolas Golse
- Department of Hepatobiliary Surgery, Hepato-Biliary Center, Paul-Brousse Hospital, Assistance Publique Hôpitaux de Paris, Villejuif, France
- Department of Pathogenesis and Treatment of Liver Diseases, Paris-Saclay University, INSERM, UMR-S 1193, Paris, France
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Bezjak M, Kocman B, Jadrijević S, Filipec Kanižaj T, Antonijević M, Dalbelo Bašić B, Mikulić D. Use of machine learning models for identification of predictors of survival and tumour recurrence in liver transplant recipients with hepatocellular carcinoma. ANNALS OF TRANSLATIONAL MEDICINE 2023; 11:345. [PMID: 37675331 PMCID: PMC10477658 DOI: 10.21037/atm-22-6469] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/20/2022] [Accepted: 05/19/2023] [Indexed: 09/08/2023]
Abstract
Background Hepatocellular carcinoma (HCC) is one of the leading indications for liver transplantation (LT) however, selection criteria remain controversial. We aimed to identify survival factors and predictors for tumour recurrence using machine learning (ML) methods. We also compared ML models to the Cox regression model. Methods Thirty pretransplant donor and recipient general and tumour specific parameters were analysed from 170 patients who underwent orthotopic liver transplantation for HCC between March 2013 and December 2019 at the University Hospital Merkur, Zagreb. Survival rates were calculated using the Kaplan-Meier method and multivariate analysis was performed using the Cox proportional hazards regression model. Data was also processed through Coxnet (a regularized Cox regression model), Random Survival Forest (RSF), Survival Support Vector Machine (SVM) and Survival Gradient Boosting models, which included pre-processing, variable selection, imputation of missing data, training and cross-validation of the models. The cross-validated concordance index (CI) was used as an evaluation metric and to determine the best performing model. Results Kaplan-Meier curves for 5-year survival time showed survival probability of 80% for recipient survival and 82% for graft survival. The 5-year HCC recurrence was observed in 19% of patients. The best predictive accuracy was observed in the RSF model with CI of 0.72, followed by the Survival SVM model (CI 0.70). Overall ML models outperform the Cox regression model with respect to their limitations. Random Forest analysis provided several relevant outcome predictors: alpha fetoprotein (AFP), donor C-reactive protein (CRP), recipient age and neutrophil to lymphocyte ratio (NLR). Cox multivariate analysis showed similarities with RSF models in identifying detrimental variables. Some variables such as donor age and number of transarterial chemoembolization treatments (TACE) were pointed out, but these were not influential in our RSF model. Conclusions Using ML methods in addition to classical statistical analysis, it is possible to develop sufficient prognostic models, which, compared to established risk scores, could help us quantify survival probability and make changes in organ utilization.
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Affiliation(s)
- Miran Bezjak
- Division of Abdominal Surgery and Organ Transplantation, Department of Surgery, University Hospital Merkur, Zagreb, Croatia
| | - Branislav Kocman
- Division of Abdominal Surgery and Organ Transplantation, Department of Surgery, University Hospital Merkur, Zagreb, Croatia
| | - Stipislav Jadrijević
- Division of Abdominal Surgery and Organ Transplantation, Department of Surgery, University Hospital Merkur, Zagreb, Croatia
| | - Tajana Filipec Kanižaj
- Division of Gastroenterology, Department of Internal Medicine, University Hospital Merkur, Zagreb, Croatia
| | | | - Bojana Dalbelo Bašić
- Faculty of Electrical Engineering and Computing, Department of Electronics, Microelectronics, Computer and Intelligent Systems, Zagreb, Croatia
| | - Danko Mikulić
- Division of Abdominal Surgery and Organ Transplantation, Department of Surgery, University Hospital Merkur, Zagreb, Croatia
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Cen X, Lu Y, Lu J, Zhan P, Cheng Y, Luo C, Liu J, Xie C, Wang F. Upregulation of helicase-like transcription factor predicts poor prognosis and facilitates hepatocellular carcinoma progression. Hum Cell 2023:10.1007/s13577-023-00917-3. [PMID: 37227687 DOI: 10.1007/s13577-023-00917-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2022] [Accepted: 05/12/2023] [Indexed: 05/26/2023]
Abstract
Helicase-like transcription factor (HLTF) belongs to the family of SWI/SNF proteins, which has been reported to exert oncogenic function in several human cancers. However, to date, its functional role in hepatocellular carcinoma (HCC) has not been revealed. Here, we found that HLTF was highly expressed in HCC tissues compared to nontumor tissues. Additionally, upregulation of HLTF was significantly associated with poor prognosis of patients with HCC. Functional experiments demonstrated that knockdown of HLTF expression significantly inhibited the proliferation, migration, and invasion of HCC cells in vitro, and suppressed tumor growth in vivo. In conclusion, our results suggest that upregulation of HLTF is associated with the development of HCC, and HLTF may be a potential therapeutic target for HCC treatment.
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Affiliation(s)
- Xuesong Cen
- Xiamen Translational Medical Key Laboratory of Digestive System Tumor, Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma, School of Medicine, Zhongshan Hospital of Xiamen University, Xiamen University, 209 South Hubin Road, Xiamen, 361004, Fujian Province, China
| | - Yuyan Lu
- Xiamen Translational Medical Key Laboratory of Digestive System Tumor, Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma, School of Medicine, Zhongshan Hospital of Xiamen University, Xiamen University, 209 South Hubin Road, Xiamen, 361004, Fujian Province, China
| | - Jing Lu
- Xiamen Translational Medical Key Laboratory of Digestive System Tumor, Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma, School of Medicine, Zhongshan Hospital of Xiamen University, Xiamen University, 209 South Hubin Road, Xiamen, 361004, Fujian Province, China
| | - Ping Zhan
- Xiamen Translational Medical Key Laboratory of Digestive System Tumor, Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma, School of Medicine, Zhongshan Hospital of Xiamen University, Xiamen University, 209 South Hubin Road, Xiamen, 361004, Fujian Province, China
| | - Yizhe Cheng
- Xiamen Translational Medical Key Laboratory of Digestive System Tumor, Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma, School of Medicine, Zhongshan Hospital of Xiamen University, Xiamen University, 209 South Hubin Road, Xiamen, 361004, Fujian Province, China
| | - Changhong Luo
- Xiamen Translational Medical Key Laboratory of Digestive System Tumor, Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma, School of Medicine, Zhongshan Hospital of Xiamen University, Xiamen University, 209 South Hubin Road, Xiamen, 361004, Fujian Province, China
| | - Jie Liu
- Xiamen Translational Medical Key Laboratory of Digestive System Tumor, Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma, School of Medicine, Zhongshan Hospital of Xiamen University, Xiamen University, 209 South Hubin Road, Xiamen, 361004, Fujian Province, China
| | - Chengrong Xie
- Xiamen Translational Medical Key Laboratory of Digestive System Tumor, Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma, School of Medicine, Zhongshan Hospital of Xiamen University, Xiamen University, 209 South Hubin Road, Xiamen, 361004, Fujian Province, China.
| | - Fuqiang Wang
- Department of Hepatobiliary Surgery, Xiamen Key Laboratory of Liver Diseases, Xiamen Hospital of Traditional Chinese Medicine, Beijing University of Chinese Medicine, 1739 Xianyue Road, Xiamen, 361001, Fujian Province, China.
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10
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Laurent C, Rayar M, Maulat C, Muscari F, Marichez A, Gregoire E, Chopinet S, Mabrut JY, Boudjema K, Lesurtel M, Adam JP, Mohkam K, Chiche L. Liver transplantation and hepatocellular carcinoma: is TIPS deleterious? A multicentric retrospective study of the ARCHET research group with propensity score matching. Langenbecks Arch Surg 2023; 408:149. [PMID: 37052722 DOI: 10.1007/s00423-023-02875-8] [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: 12/16/2021] [Accepted: 03/30/2023] [Indexed: 04/14/2023]
Abstract
PURPOSE A transjugular intrahepatic portosystemic shunt (TIPS) before the liver transplantation (LT) has been considered a contraindication in cases of hepatocellular carcinoma (HCC) because of the risk of tumour growth. We aimed to assess the impact of TIPS on incidental HCC and oncological outcomes in transplanted patients with pre-existing HCC. METHODS All consecutive transplanted patients for cirrhosis who had a previous TIPS with or without HCC were included. Between 2007 and 2014, 1912 patients were transplanted. We included 122 (6.3%) patients having TIPS before LT. A 1:3 matched cohort of 366 patients (18.9%) having LT without previous TIPS was selected using a propensity score. Incidental HCC rate and risk factor of HCC recurrence were evaluated using multivariate analysis with a competing risk model. RESULTS Before LT, in the TIPS group, 27 (22.1%) had an HCC vs. 81 (22.1%) in the control group (p = 1). The incidental HCC rate was similar: 10.5% (10/95) in the TIPS group vs. 6.3% (18/285) in the control group (p = 0.17). Recurrence occurred in 1/27 (3.7%) patient in the TIPS group and in 7/81 (8.6%) patients in the control group, without significant difference (p = 0.51). After multivariate regression, patient's gender (p < 0.01) was significantly associated with HCC recurrence while a tumour within Milan criteria (p = 0.01, sHR: 0.17 [0.04; 0.7]) and an incidental HCC (p<0.01) were found to be protector factors against HCC recurrence. CONCLUSION TIPS did not worsen the prognosis of transplanted patients for HCC. TIPS should no longer be contraindicated for oncological reasons in patients with HCC waiting for an LT.
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Affiliation(s)
- Christophe Laurent
- Department of Digestive Surgery and Liver Transplantation, Bordeaux University Hospital, Pessac, France.
| | - Michel Rayar
- Department of Visceral Surgery, University Hospital of Rennes, Rennes, France
| | - Charlotte Maulat
- Department of Visceral Surgery, Toulouse-Rangueil University Hospital, Toulouse, France
| | - Fabrice Muscari
- Department of Visceral Surgery, Toulouse-Rangueil University Hospital, Toulouse, France
| | - Arthur Marichez
- Department of Digestive Surgery and Liver Transplantation, Bordeaux University Hospital, Pessac, France
| | - Emilie Gregoire
- Department of General Surgery and Liver Transplantation, Hôpital de la Timone, Aix-Marseille University, Marseille, France
| | - Sophie Chopinet
- Department of General Surgery and Liver Transplantation, Hôpital de la Timone, Aix-Marseille University, Marseille, France
| | - Jean Yves Mabrut
- Department of General Surgery & Liver Transplantation, Hospices Civils de Lyon, Croix-Rousse University Hospital, Claude-Bernard Lyon 1 University, Lyon, France
| | - Karim Boudjema
- Department of Visceral Surgery, University Hospital of Rennes, Rennes, France
| | - Mickael Lesurtel
- Department of General Surgery & Liver Transplantation, Hospices Civils de Lyon, Croix-Rousse University Hospital, Claude-Bernard Lyon 1 University, Lyon, France
| | - Jean-Philippe Adam
- Department of Digestive Surgery and Liver Transplantation, Bordeaux University Hospital, Pessac, France
| | - Kayvan Mohkam
- Department of General Surgery & Liver Transplantation, Hospices Civils de Lyon, Croix-Rousse University Hospital, Claude-Bernard Lyon 1 University, Lyon, France
| | - Laurence Chiche
- Department of Digestive Surgery and Liver Transplantation, Bordeaux University Hospital, Pessac, France
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11
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Sha M, Chen C, Shen C, Jeong S, Sun HY, Xu N, Hang HL, Cao J, Tong Y. Clinical analysis of deceased donor liver transplantation in the treatment of hepatocellular carcinoma with segmental portal vein tumor thrombus: A long-term real-world study. Front Oncol 2022; 12:971532. [PMID: 36203429 PMCID: PMC9530398 DOI: 10.3389/fonc.2022.971532] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Accepted: 08/24/2022] [Indexed: 11/13/2022] Open
Abstract
Background Hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) have conventionally been regarded as a contraindication for liver transplantation (LT). However, the outcomes of deceased donor liver transplantation (DDLT) in patients with segmental PVTT remain unknown. The aim of this study is to evaluate the feasibility and effectiveness of DDLT in the treatment of HCC with segmental PVTT. Methods We retrospectively analyzed 254 patients who underwent DDLT for HCC in our institution from January 2015 to November 2019. To assess the risks of PVTT, various clinicopathological variables were evaluated. Overall (OS) and recurrence-free survival (RFS) analyses based on different PVTT types were performed in HCC patients. Results Of the 254 patients, a total of 46 patients had PVTT, of whom 35 had lobar PVTT and 11 had segmental PVTT in second-order branches or below. Alpha-fetoprotein (AFP) level, tumor maximal diameter, histological grade, micro-vascular invasion (MVI), RFS, and OS were significantly different between the control and PVTT groups. Lobar PVTT was associated with unfavorable 5-year RFS and OS compared with MVI group (28.6% and 17.1%, respectively). Instead, no significant difference was observed between the segmental PVTT and MVI group in terms of 5-year RFS and OS (RFS: 36.4% vs. 40.4%, p=0.667; OS: 54.5% vs. 45.1%, p=0.395). Further subgroup analysis showed segmental PVTT with AFP levels ≤100 ng/ml presented significantly favorable RFS and OS rates than those with AFP level >100 ng/ml (p=0.050 and 0.035, respectively). Conclusions In summary, lobar PVTT remains a contraindication to DDLT. HCC patients with segmental PVTT and AFP level ≤100 ng/ml may be acceptable candidates for DDLT.
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Affiliation(s)
- Meng Sha
- Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Chen Chen
- Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Chuan Shen
- Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Seogsong Jeong
- Department of Biomedical Informatics, CHA University School of Medicine, CHA University, Seongnam, South Korea
- Institute of Basic Medical Sciences, School of Medicine, CHA University, Seongnam, South Korea
- Institute for Biomedical Informatics, School of Medicine, CHA University, Seongnam, South Korea
| | - Han-yong Sun
- Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Ning Xu
- Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Hua-lian Hang
- Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Jie Cao
- Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Ying Tong
- Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- *Correspondence: Ying Tong,
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12
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Sun LY, Cen WJ, Tang WT, Deng L, Wang F, Ji XM, Yang JJ, Zhang RJ, Zhang XH, Du ZM. Alpha-Fetoprotein Ratio Predicts Alpha-Fetoprotein Positive Hepatocellular Cancer Patient Prognosis after Hepatectomy. DISEASE MARKERS 2022; 2022:7640560. [PMID: 35059044 PMCID: PMC8766187 DOI: 10.1155/2022/7640560] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/09/2021] [Accepted: 12/22/2021] [Indexed: 11/21/2022]
Abstract
BACKGROUND This study was conducted to investigate the effect of alpha-fetoprotein (AFP) ratio on the prognosis of AFP-positive hepatocellular carcinoma (HCC) patients after hepatectomy. METHODS We retrospectively included 879 HCC patients with AFP-positive who underwent hepatectomy from February 2012 to October 2017 and randomly divided into training cohort and validation cohort. AFP ratio was equal to the AFP level within one week before hepatectomy to AFP level within 20-40 days after surgery. The end point of follow-up was disease-free survival (DFS) and overall survival (OS). RESULTS AFP ratio was not associated with clinical characteristics in training cohort and validation cohort. According to the X-tile software, the optimum cut-off point was 17.8 for AFP ratio. Significant differences between AFP ratio high and AFP ratio low were observed in DFS and OS in both cohort (p < 0.05). Kaplan-Meier curves and receiver-operating curves were showed that AFP ratio was better than AFP level preoperation in predicting the prognosis of AFP-positive HCC patients after hepatectomy. The multivariate analysis demonstrated that AFP ratio was a significant independent risk factor for both OS and DFS in HCC patients with AFP-positive. CONCLUSIONS AFP ratio might be a prognosis predictor for HCC patients with AFP-positive after hepatectomy.
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Affiliation(s)
- Li-Yue Sun
- Second Department of Oncology, Guangdong Second Provincial General Hospital, 466 Xingang-Zhong Road, Guangzhou, China
| | - Wen-Jian Cen
- State Key Laboratory of Oncology in South China, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
- Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Wen-Ting Tang
- State Key Laboratory of Oncology in South China, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
- Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Ling Deng
- State Key Laboratory of Oncology in South China, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
- Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Fang Wang
- State Key Laboratory of Oncology in South China, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
- Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Xiao-Meng Ji
- State Key Laboratory of Oncology in South China, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
- Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Jiao-Jiao Yang
- State Key Laboratory of Oncology in South China, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
- Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Ren-Jing Zhang
- State Key Laboratory of Oncology in South China, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
- Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Xu-Hui Zhang
- Second Department of Oncology, Guangdong Second Provincial General Hospital, 466 Xingang-Zhong Road, Guangzhou, China
| | - Zi-Ming Du
- State Key Laboratory of Oncology in South China, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
- Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou, China
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Magro B, Pinelli D, De Giorgio M, Lucà MG, Ghirardi A, Carrobio A, Baronio G, Del Prete L, Nounamo F, Gianatti A, Colledan M, Fagiuoli S. Pre-Transplant Alpha-Fetoprotein > 25.5 and Its Dynamic on Waitlist Are Predictors of HCC Recurrence after Liver Transplantation for Patients Meeting Milan Criteria. Cancers (Basel) 2021; 13:5976. [PMID: 34885087 PMCID: PMC8656660 DOI: 10.3390/cancers13235976] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2021] [Revised: 11/22/2021] [Accepted: 11/25/2021] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND AND AIM Hepatocellular carcinoma (HCC) recurrence rates after liver transplantation (LT) range between 8 and 20%. Alpha-fetoprotein (AFP) levels at transplant can predict HCC recurrence, however a defined cut-off value is needed to better stratify patients. The aim of this study was to evaluate the rate of HCC recurrence at our centre and to identify predictors, focusing on AFP. METHODS We retrospectively analysed 236 consecutive patients that were waitlisted for HCC who all met the Milan criteria from January 2001 to December 2017 at our liver transplant centre. A total of twenty-nine patients dropped out while they were waitlisted, and 207 patients were included in the final analysis. All survival analyses included the competing-risk model. RESULTS The mean age was 56.8 ± 6.8 years. A total of 14% were female (n = 29/207). The median MELD (model for end-stage liver disease) at LT was 12 (9-16). The median time on the waitlist was 92 (41-170) days. The HCC recurrence rate was 16.4% (n = 34/208). The mean time to recurrence was 3.3 ± 2.8 years. The median AFP levels at transplant were higher in patients with HCC recurrence (p < 0.001). At multivariate analysis, the AFP value at transplant that was greater than 25.5 ng/mL (AUC 0.69) was a strong predictor of HCC recurrence after LT [sHR 3.3 (1.6-6.81); p = 0.001]. The HCC cumulative incidence function (CIF) of recurrence at 10 years from LT was significantly higher in patients with AFP > 25.5 ng/mL [34.3% vs. 11.5% (p = 0.001)]. Moreover, an increase in AFP > 20.8%, was significantly associated with HCC recurrence (p = 0.034). CONCLUSIONS In conclusion, in our retrospective study, the AFP level at transplant > 25.5 ng/mL and its increase greater than 20.8% on the waitlist were strong predictors of HCC recurrence after LT in a cohort of patients that were waitlisted within the Milan criteria. However further studies are needed to validate these data.
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Affiliation(s)
- Bianca Magro
- Gastroenterology, Hepatology and Liver Transplantation, Department of Medicine-Papa Giovanni, XXIII Hospital, 24122 Bergamo, Italy; (M.D.G.); (M.G.L.); (S.F.)
| | - Domenico Pinelli
- Unit of Hepato-Biliary Surgery and Liver Transplantation, ASST Papa Giovanni XXIII, 24122 Bergamo, Italy; (D.P.); (G.B.); (L.D.P.); (F.N.); (M.C.)
| | - Massimo De Giorgio
- Gastroenterology, Hepatology and Liver Transplantation, Department of Medicine-Papa Giovanni, XXIII Hospital, 24122 Bergamo, Italy; (M.D.G.); (M.G.L.); (S.F.)
| | - Maria Grazia Lucà
- Gastroenterology, Hepatology and Liver Transplantation, Department of Medicine-Papa Giovanni, XXIII Hospital, 24122 Bergamo, Italy; (M.D.G.); (M.G.L.); (S.F.)
| | - Arianna Ghirardi
- FROM Research Foundation, Papa Giovanni XXIII Hospital, 24122 Bergamo, Italy; (A.G.); (A.C.)
| | - Alessandra Carrobio
- FROM Research Foundation, Papa Giovanni XXIII Hospital, 24122 Bergamo, Italy; (A.G.); (A.C.)
| | - Giuseppe Baronio
- Unit of Hepato-Biliary Surgery and Liver Transplantation, ASST Papa Giovanni XXIII, 24122 Bergamo, Italy; (D.P.); (G.B.); (L.D.P.); (F.N.); (M.C.)
| | - Luca Del Prete
- Unit of Hepato-Biliary Surgery and Liver Transplantation, ASST Papa Giovanni XXIII, 24122 Bergamo, Italy; (D.P.); (G.B.); (L.D.P.); (F.N.); (M.C.)
| | - Franck Nounamo
- Unit of Hepato-Biliary Surgery and Liver Transplantation, ASST Papa Giovanni XXIII, 24122 Bergamo, Italy; (D.P.); (G.B.); (L.D.P.); (F.N.); (M.C.)
| | - Andrea Gianatti
- Pathology Unit, ASST Papa Giovanni XXIII, 24122 Bergamo, Italy;
| | - Michele Colledan
- Unit of Hepato-Biliary Surgery and Liver Transplantation, ASST Papa Giovanni XXIII, 24122 Bergamo, Italy; (D.P.); (G.B.); (L.D.P.); (F.N.); (M.C.)
| | - Stefano Fagiuoli
- Gastroenterology, Hepatology and Liver Transplantation, Department of Medicine-Papa Giovanni, XXIII Hospital, 24122 Bergamo, Italy; (M.D.G.); (M.G.L.); (S.F.)
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Tu HB, Chen LH, Huang YJ, Feng SY, Lin JL, Zeng YY. Novel model combining contrast-enhanced ultrasound with serology predicts hepatocellular carcinoma recurrence after hepatectomy. World J Clin Cases 2021; 9:7009-7021. [PMID: 34540956 PMCID: PMC8409194 DOI: 10.12998/wjcc.v9.i24.7009] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2021] [Revised: 06/12/2021] [Accepted: 07/05/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Surgery is the primary curative option in patients with hepatocellular carcinoma (HCC). However, recurrence within 2 years is observed in 30%-50% of patients, being a major cause of mortality. AIM To construct and verify a non-invasive prediction model combining contrast-enhanced ultrasound (CEUS) with serology biomarkers to predict the early recurrence of HCC. METHODS Records of 744 consecutive patients undergoing first-line curative surgery for HCC in one institution from 2016-2018 were reviewed, and 292 local patients were selected for analysis. General characteristics including gender and age, CEUS liver imaging reporting and data system (LIRADS) parameters including wash-in time, wash-in type, wash-out time, and wash-out type, and serology biomarkers including alanine aminotransferase, aspartate aminotransferase, platelets, and alpha-fetoprotein (AFP) were collected. Univariate analysis and multivariate Cox proportional hazards regression model were used to evaluate the independent prognostic factors for tumor recurrence. Then a nomogram called CEUS model was constructed. The CEUS model was then used to predict recurrence at 6 mo, 12 mo, and 24 mo, the cut-off value was calculate by X-tile, and each C-index was calculated. Then Kaplan-Meier curve was compared by log-rank test. The calibration curves of each time were depicted. RESULTS A nomogram predicting early recurrence (ER), named CEUS model, was formulated based on the results of the multivariate Cox regression analysis. This nomogram incorporated tumor diameter, preoperative AFP level, and LIRADS, and the hazard ratio was 1.123 (95% confidence interval [CI]: 1.041-1.211), 1.547 (95%CI: 1.245-1.922), and 1.428 (95%CI: 1.059-1.925), respectively. The cut-off value at 6 mo, 12 mo, and 24 mo was 100, 80, and 50, and the C-index was 0.748 (95%CI: 0.683-0.813), 0.762 (95%CI: 0.704-0.820), and 0.762 (95%CI: 0.706-0.819), respectively. The model showed satisfactory results, and the calibration at 6 mo was desirable; however, the calibration at 12 and 24 mo should be improved. CONCLUSION The CEUS model enables the well-calibrated individualized prediction of ER before surgery and may represent a novel tool for biomarker research and individual counseling.
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Affiliation(s)
- Hai-Bin Tu
- Department of Ultrasound, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, Fujian Province, China
| | - Li-Hong Chen
- Department of Ultrasound, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, Fujian Province, China
| | - Yu-Jie Huang
- Department of Ultrasound, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, Fujian Province, China
| | - Si-Yi Feng
- Department of Ultrasound, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, Fujian Province, China
| | - Jian-Ling Lin
- Department of Ultrasound, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, Fujian Province, China
| | - Yong-Yi Zeng
- Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, Fujian Province, China
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15
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Ferstl PG, Filmann N, Heilgenthal EM, Schnitzbauer AA, Bechstein WO, Kempf VAJ, Villinger D, Schultze TG, Hogardt M, Stephan C, Mutlak H, Weiler N, Mücke MM, Trebicka J, Zeuzem S, Waidmann O, Welker MW. Colonization with multidrug-resistant organisms is associated with in increased mortality in liver transplant candidates. PLoS One 2021; 16:e0245091. [PMID: 33481811 PMCID: PMC7822319 DOI: 10.1371/journal.pone.0245091] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2020] [Accepted: 12/21/2020] [Indexed: 02/07/2023] Open
Abstract
Objectives Rising prevalence of multidrug-resistant organisms (MDRO) is a major health problem in patients with liver cirrhosis. The impact of MDRO colonization in liver transplantation (LT) candidates and recipients on mortality has not been determined in detail. Methods Patients consecutively evaluated and listed for LT in a tertiary German liver transplant center from 2008 to 2018 underwent screening for MDRO colonization including methicillin-resistant Staphylococcus aureus (MRSA), multidrug-resistant gram-negative bacteria (MDRGN), and vancomycin-resistant enterococci (VRE). MDRO colonization and infection status were obtained at LT evaluation, planned and unplanned hospitalization, three months upon graft allocation, or at last follow-up on the waiting list. Results In total, 351 patients were listed for LT, of whom 164 (47%) underwent LT after a median of 249 (range 0–1662) days. Incidence of MDRO colonization increased during waiting time for LT, and MRDO colonization was associated with increased mortality on the waiting list (HR = 2.57, p<0.0001. One patients was colonized with a carbapenem-resistant strain at listing, 9 patients acquired carbapenem-resistant gram-negative bacteria (CRGN) on the waiting list, and 4 more after LT. In total, 10 of these 14 patients died. Conclusions Colonization with MDRO is associated with increased mortality on the waiting list, but not in short-term follow-up after LT. Moreover, colonization with CRGN seems associated with high mortality in liver transplant candidates and recipients.
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Affiliation(s)
- Philip G. Ferstl
- Department for Internal Medicine I / Gastroenterology and Hepatology, University Hospital, Goethe University, Frankfurt am Main, Germany
- * E-mail:
| | - Natalie Filmann
- Institute of Biostatistics and Mathematical Modeling, Goethe University, Frankfurt am Main, Frankfurt, Germany
| | - Eva-Maria Heilgenthal
- Department for Internal Medicine I / Gastroenterology and Hepatology, University Hospital, Goethe University, Frankfurt am Main, Germany
| | - Andreas A. Schnitzbauer
- Department of General and Visceral Surgery, University Hospital, Goethe University, Frankfurt am Main, Germany
| | - Wolf O. Bechstein
- Department of General and Visceral Surgery, University Hospital, Goethe University, Frankfurt am Main, Germany
| | - Volkhard A. J. Kempf
- Institute for Medical Microbiology and Infection Control, University Hospital, Goethe University, Frankfurt am Main, Germany
- University Center for Infectious Diseases (UCI), University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany
- University Center of Competence for Infection Control of the State of Hesse, Frankfurt Main, Germany
| | - David Villinger
- Institute for Medical Microbiology and Infection Control, University Hospital, Goethe University, Frankfurt am Main, Germany
- University Center for Infectious Diseases (UCI), University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany
- University Center of Competence for Infection Control of the State of Hesse, Frankfurt Main, Germany
| | - Tilman G. Schultze
- Institute for Medical Microbiology and Infection Control, University Hospital, Goethe University, Frankfurt am Main, Germany
- University Center for Infectious Diseases (UCI), University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany
- University Center of Competence for Infection Control of the State of Hesse, Frankfurt Main, Germany
| | - Michael Hogardt
- Institute for Medical Microbiology and Infection Control, University Hospital, Goethe University, Frankfurt am Main, Germany
- University Center for Infectious Diseases (UCI), University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany
- University Center of Competence for Infection Control of the State of Hesse, Frankfurt Main, Germany
| | - Christoph Stephan
- Department for Internal Medicine II / Infectious Diseases, University Hospital, Goethe University, Frankfurt am Main, Germany
| | - Haitham Mutlak
- Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital, Goethe University, Frankfurt am Main, Germany
| | - Nina Weiler
- Department for Internal Medicine I / Gastroenterology and Hepatology, University Hospital, Goethe University, Frankfurt am Main, Germany
| | - Marcus M. Mücke
- Department for Internal Medicine I / Gastroenterology and Hepatology, University Hospital, Goethe University, Frankfurt am Main, Germany
| | - Jonel Trebicka
- Department for Internal Medicine I / Gastroenterology and Hepatology, University Hospital, Goethe University, Frankfurt am Main, Germany
| | - Stefan Zeuzem
- Department for Internal Medicine I / Gastroenterology and Hepatology, University Hospital, Goethe University, Frankfurt am Main, Germany
| | - Oliver Waidmann
- Department for Internal Medicine I / Gastroenterology and Hepatology, University Hospital, Goethe University, Frankfurt am Main, Germany
| | - Martin-Walter Welker
- Department for Internal Medicine I / Gastroenterology and Hepatology, University Hospital, Goethe University, Frankfurt am Main, Germany
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