|
1
|
Han JW, Choi JY, Jung ES, Kim JH, Cho HS, Yoo JS, Sung PS, Jang JW, Yoon SK, Choi HJ, You YK. Association between the early high level of serum tacrolimus and recurrence of hepatocellular carcinoma in ABO-incompatible liver transplantation. World J Gastrointest Surg 2023; 15:2727-2738. [PMID: 38222009 PMCID: PMC10784835 DOI: 10.4240/wjgs.v15.i12.2727] [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: 09/11/2023] [Revised: 10/18/2023] [Accepted: 12/01/2023] [Indexed: 12/27/2023] Open
Abstract
BACKGROUND Clinical factors predicting graft survival (GS) after ABO-incompatible (ABOi) liver transplantation (LT), and differences between recipients with and without hepatocellular carcinoma (HCC) are unclear. AIM To analyze the impact of serial serum tacrolimus trough concentration in recipients with or without HCC) in ABOi living-donor liver transplantation (LDLT). METHODS We analyzed a historical cohort of 89 recipients who underwent ABOi LDLT, including 47 patients with HCC. RESULTS The 1-, 3-, 5-, and 10-year GS rates were 85.9%, 73.3%, 71.4%, and 71.4%, respectively, and there were no significant differences between HCC and non-HCC recipients. In multivariate Cox-regression analyses, tacrolimus trough concentrations below 5.4 ng/mL at 24 wk post-LT, in addition to the antibody-mediated rejection (AMR) were associated with poor-graft outcomes. In HCC patients, AMR [hazard ratio (HR) = 63.20, P < 0.01] and HCC recurrence (HR = 20.72, P = 0.01) were significantly associated with poor graft outcomes. HCCs outside Milan criteria, and tacrolimus concentrations at 4 wk post-LT > 7.3 ng/mL were significant predictive factors for HCC recurrence. After propensity score matching, patients with high tacrolimus concentrations at 4 wk had significantly poor recurrence-free survival. CONCLUSION Elevated tacrolimus levels at 4 wk after ABOi LDLT have been found to correlate with HCC recurrence. Therefore, careful monitoring and control of tacrolimus levels are imperative in ABOi LT recipients with HCC.
Collapse
Affiliation(s)
- Ji Won Han
- Department of Internal Medicine, The Catholic University of Korea, Seoul 06591, South Korea
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea
| | - Jong Young Choi
- Department of Internal Medicine, The Catholic University of Korea, Seoul 06591, South Korea
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea
| | - Eun Sun Jung
- Department of Hospital Pathology, The Catholic University of Korea, Seoul 06591, South Korea
| | - Ji Hoon Kim
- Department of Internal Medicine, The Catholic University of Korea, Seoul 06591, South Korea
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea
| | - Hee Sun Cho
- Department of Internal Medicine, The Catholic University of Korea, Seoul 06591, South Korea
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea
| | - Jae-Sung Yoo
- Department of Internal Medicine, The Catholic University of Korea, Seoul 06591, South Korea
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea
| | - Pil Soo Sung
- Department of Internal Medicine, The Catholic University of Korea, Seoul 06591, South Korea
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea
| | - Jeong Won Jang
- Department of Internal Medicine, The Catholic University of Korea, Seoul 06591, South Korea
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea
| | - Seung Kew Yoon
- Department of Internal Medicine, The Catholic University of Korea, Seoul 06591, South Korea
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea
| | - Ho Joong Choi
- Department of Surgery, The Catholic University of Korea, Seoul 06591, South Korea
| | - Young Kyoung You
- Department of Surgery, The Catholic University of Korea, Seoul 06591, South Korea
| |
Collapse
|
|
2
|
Li FY, Li JG, Wu SS, Ye HL, He XQ, Zeng QJ, Zheng RQ, An C, Li K. An Optimal Ablative Margin of Small Single Hepatocellular Carcinoma Treated with Image-Guided Percutaneous Thermal Ablation and Local Recurrence Prediction Base on the Ablative Margin: A Multicenter Study. J Hepatocell Carcinoma 2021; 8:1375-1388. [PMID: 34815974 PMCID: PMC8604653 DOI: 10.2147/jhc.s330746] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Accepted: 10/26/2021] [Indexed: 01/05/2023] Open
Abstract
Objective To explore the best ablative margin (AM) for single hepatocellular carcinoma (HCC) patients with image-guided percutaneous thermal ablation (IPTA) based on MRI–MRI fusion imaging, and to develop and validate a local tumor progression (LTP) predictive model based on the recommended AM. Methods Between March 2014 and August 2019, 444 treatment-naïve patients with single HCC (diameter ≤3 cm) who underwent IPTA as first-line treatment from three hospitals were included, which were randomly divided into training (n= 296) and validation (n = 148) cohorts. We measured the ablative margin (AM) by MRI–MRI fusion imaging based on pre-ablation and post-ablation images. Then, we followed up their LPT and verified the optimal AM. Risk factors related to LTP were explored through Cox regression models, the nomogram was developed to predict the LTP risk base on the risk factors, and subsequently validated. The predictive performance and discrimination were assessed and compared with conventional indices. Results The median follow-up was 19.9 months (95% CI 18.0–21.8) for the entire cohort. The results revealed that the tumor size (HR: 2.16; 95% CI 1.25–3.72; P = 0.003) and AM (HR: 0.72; 95% CI, 0.61–0.85; P < 0.001) were independent prognostic factors for LTP. The AM had a pronounced nonlinear impact on LTP, and a cut-off value of 5-mm was optimal. We developed and validated an LTP predictive model based on the linear tumor size and nonlinear AM. The model showed good predictive accuracy and discrimination (training set, concordance index [C-index] of 0.751; validation set, C-index of 0.756) and outperformed other conventional indices. Conclusion The 5-mm AM is recommended for the best IPTA candidates with single HCC (diameter ≤3 cm). We provided an LTP predictive model that exhibited adequate performance for individualized prediction and risk stratification.
Collapse
Affiliation(s)
- Feng-Yao Li
- Department of Ultrasound, Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Jian-Guo Li
- The Department of Infectious Disease,The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Song-Song Wu
- Shengli Clinical Medical College of Fujian Medical University, Department of Ultrasonography,Fujian Provincial Hospital, Fuzhou, People's Republic of China
| | - Huo-Lin Ye
- Department of Ultrasound, Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Xu-Qi He
- Department of Ultrasound, Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Qing-Jing Zeng
- Department of Ultrasound, Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Rong-Qin Zheng
- Department of Ultrasound, Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Chao An
- Department of Minimal Invasive Intervention, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China
| | - Kai Li
- Department of Ultrasound, Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China
| |
Collapse
|
|
3
|
Robb TJ, Tse R, Blenkiron C. Reviving the Autopsy for Modern Cancer Evolution Research. Cancers (Basel) 2021; 13:409. [PMID: 33499137 PMCID: PMC7866143 DOI: 10.3390/cancers13030409] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Revised: 01/14/2021] [Accepted: 01/20/2021] [Indexed: 12/14/2022] Open
Abstract
Outstanding questions plaguing oncologists, centred around tumour evolution and heterogeneity, include the development of treatment resistance, immune evasion, and optimal drug targeting strategies. Such questions are difficult to study in limited cancer tissues collected during a patient's routine clinical care, and may be better investigated in the breadth of cancer tissues that may be permissible to collect during autopsies. We are starting to better understand key tumour evolution challenges based on advances facilitated by autopsy studies completed to date. This review article explores the great progress in understanding that cancer tissues collected at autopsy have already enabled, including the shared origin of metastatic cells, the importance of early whole-genome doubling events for amplifying genes needed for tumour survival, and the creation of a wealth of tissue resources powered to answer future questions, including patient-derived xenografts, cell lines, and a wide range of banked tissues. We also highlight the future role of these programmes in advancing our understanding of cancer evolution. The research autopsy provides a special opportunity for cancer patients to give the ultimate gift-to selflessly donate their tissues towards better cancer care.
Collapse
Affiliation(s)
- Tamsin Joy Robb
- Department of Molecular Medicine and Pathology, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1051, New Zealand;
| | - Rexson Tse
- Department of Forensic Pathology, LabPLUS, Auckland City Hospital, Auckland 1051, New Zealand;
| | - Cherie Blenkiron
- Department of Molecular Medicine and Pathology, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1051, New Zealand;
- Auckland Cancer Society Research Centre, University of Auckland, Auckland 1051, New Zealand
| |
Collapse
|
|
4
|
Zhang Q, Lou Y, Bai XL, Liang TB. Intratumoral heterogeneity of hepatocellular carcinoma: From single-cell to population-based studies. World J Gastroenterol 2020; 26:3720-3736. [PMID: 32774053 PMCID: PMC7383842 DOI: 10.3748/wjg.v26.i26.3720] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Revised: 06/02/2020] [Accepted: 06/18/2020] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is characterized by high heterogeneity in both intratumoral and interpatient manners. While interpatient heterogeneity is related to personalized therapy, intratumoral heterogeneity (ITH) largely influences the efficacy of therapies in individuals. ITH contributes to tumor growth, metastasis, recurrence, and drug resistance and consequently limits the prognosis of patients with HCC. There is an urgent need to understand the causes, characteristics, and consequences of tumor heterogeneity in HCC for the purposes of guiding clinical practice and improving survival. Here, we summarize the studies and technologies that describe ITH in HCC to gain insight into the origin and evolutionary process of heterogeneity. In parallel, evidence is collected to delineate the dynamic relationship between ITH and the tumor ecosystem. We suggest that conducting comprehensive studies of ITH using single-cell approaches in temporal and spatial dimensions, combined with population-based clinical trials, will help to clarify the clinical implications of ITH, develop novel intervention strategies, and improve patient prognosis.
Collapse
Affiliation(s)
- Qi Zhang
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
- Key Laboratory of Pancreatic Disease of Zhejiang Province, Hangzhou 310003, Zhejiang Province, China
- Innovation Center for the Study of Pancreatic Diseases of Zhejiang Province, Hangzhou 310003, Zhejiang Province, China
- Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou 310003, Zhejiang Province, China
| | - Yu Lou
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
- Key Laboratory of Pancreatic Disease of Zhejiang Province, Hangzhou 310003, Zhejiang Province, China
| | - Xue-Li Bai
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
- Key Laboratory of Pancreatic Disease of Zhejiang Province, Hangzhou 310003, Zhejiang Province, China
- Innovation Center for the Study of Pancreatic Diseases of Zhejiang Province, Hangzhou 310003, Zhejiang Province, China
- Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou 310003, Zhejiang Province, China
| | - Ting-Bo Liang
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
- Key Laboratory of Pancreatic Disease of Zhejiang Province, Hangzhou 310003, Zhejiang Province, China
- Innovation Center for the Study of Pancreatic Diseases of Zhejiang Province, Hangzhou 310003, Zhejiang Province, China
- Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou 310003, Zhejiang Province, China
| |
Collapse
|
|
5
|
Abstract
Hepatocellular carcinoma (HCC), the most common form of primary liver cancer, typically develops on the background of chronic liver disease and is an aggressive disease with dismal prognosis. Studies using next-generation sequencing of multiple regions of the same tumour nodule suggest different patterns of HCC evolution and confirm the high molecular heterogeneity in a subset of patients. Different hypotheses have been proposed to explain tumour evolution, including clonal selection or neutral and punctuated acquisition of genetic alterations. In parallel, data indicate a fundamental contribution of nonmalignant cells of the tumour microenvironment to cancer clonal evolution. Delineating these dynamics is crucial to improve the treatment of patients with HCC, and particularly to help understand how HCC evolution drives resistance to systemic therapies. A number of new minimally invasive techniques, such as liquid biopsies, could help track cancer evolution in HCC. These tools might improve our understanding of how systemic therapies affect tumour clonal composition and could facilitate implementation of real-time molecular monitoring of patients with HCC.
Collapse
|
|
6
|
Rebouissou S, Nault JC. Advances in molecular classification and precision oncology in hepatocellular carcinoma. J Hepatol 2020; 72:215-229. [PMID: 31954487 DOI: 10.1016/j.jhep.2019.08.017] [Citation(s) in RCA: 326] [Impact Index Per Article: 65.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2019] [Revised: 07/16/2019] [Accepted: 08/06/2019] [Indexed: 02/08/2023]
Abstract
Hepatocellular carcinoma (HCC) arises from hepatocytes through the sequential accumulation of multiple genomic and epigenomic alterations resulting from Darwinian selection. Genes from various signalling pathways such as telomere maintenance, Wnt/β-catenin, P53/cell cycle regulation, oxidative stress, epigenetic modifiers, AKT/mTOR and MAP kinase are frequently mutated in HCC. Several subclasses of HCC have been identified based on transcriptomic dysregulation and genetic alterations that are closely related to risk factors, pathological features and prognosis. Undoubtedly, integration of data obtained from both preclinical models and human studies can help to accelerate the identification of robust predictive biomarkers of response to targeted biotherapy and immunotherapy. The aim of this review is to describe the main advances in HCC in terms of molecular biology and to discuss how this knowledge could be used in clinical practice in the future.
Collapse
Affiliation(s)
- Sandra Rebouissou
- Centre de Recherche des Cordeliers, Sorbonne Université, Inserm, USPC, Université Paris Descartes, Université Paris Diderot, Université Paris 13, Functional Genomics of Solid Tumors Laboratory, F-75006 Paris, France
| | - Jean-Charles Nault
- Centre de Recherche des Cordeliers, Sorbonne Université, Inserm, USPC, Université Paris Descartes, Université Paris Diderot, Université Paris 13, Functional Genomics of Solid Tumors Laboratory, F-75006 Paris, France; Liver Unit, Hôpital Jean Verdier, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, Bondy, France; Unité de Formation et de Recherche Santé Médecine et Biologie Humaine, Université Paris 13, Communauté d'Universités et Etablissements Sorbonne Paris Cité, Paris, France.
| |
Collapse
|
|
7
|
The strengths and weaknesses of gross and histopathological evaluation in hepatocellular carcinoma: a brief review. SURGICAL AND EXPERIMENTAL PATHOLOGY 2019. [DOI: 10.1186/s42047-019-0047-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
|