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103. Circulating tumor cells: A step toward precision medicine in hepatocellular carcinoma

Author

Teng, Pai‐Chi, Agopian, Vatche G, Lin, Ting‐Yi, You, Sungyong, Zhu, Yazhen, Tseng, Hsian‐Rong, and Yang, Ju Dong

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Liver Disease, Rare Diseases, Clinical Research, Cancer, Liver Cancer, Digestive Diseases, Genetics, 4.2 Evaluation of markers and technologies, Detection, screening and diagnosis, 4.1 Discovery and preclinical testing of markers and technologies, Good Health and Well Being, Biomarkers, Biomarkers, Tumor, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Neoplastic Cells, Circulating, Precision Medicine, Prospective Studies, biomarker, circulating tumor cell, CTC digital scoring, CTC enumeration, hepatocellular carcinoma, Clinical Sciences, Gastroenterology & Hepatology, Clinical sciences
Abstract

Serum alpha-fetoprotein and radiologic imaging are the most commonly used tests for early diagnosis and dynamic monitoring of treatment response in hepatocellular carcinoma (HCC). However, the accuracy of these tests is limited, and they may not reflect the underlying biology of the tumor. Thus, developing highly accurate novel HCC biomarkers reflecting tumor biology is a clinically unmet need. Circulating tumor cells (CTCs) have long been proposed as a noninvasive biomarker in clinical oncology. Most CTC assays utilize immunoaffinity-based, size-based, and/or enrichment-free mechanisms followed by immunocytochemical staining to characterize CTCs. The prognostic value of HCC CTC enumeration has been extensively validated. Subsets of CTCs expressing mesenchymal markers are also reported to have clinical significance. In addition, researchers have been devoting their efforts to molecular characterizations of CTCs (e.g. genetics and transcriptomics) as molecular profiling can offer a more accurate readout and provide biological insights. As new molecular profiling techniques, such as digital polymerase chain reaction, are developed to detect minimal amounts of DNA/RNA, several research groups have established HCC CTC digital scoring systems to quantify clinically relevant gene panels. Given the versatility of CTCs to provide intact molecular and functional data that reflects the underlying tumor, CTCs have great potential as a noninvasive biomarker in HCC. Large-scale, prospective studies for HCC CTCs with a standardized protocol are necessary for successful clinical translation.

Published
2022

104. Comparing Low- or Standard-Dose Alteplase in Endovascular Thrombectomy: Insights From a Nationwide Registry

Author

Chen, Chih-Hao, Lee, Chung-Wei, Hsieh, Yi-Chen, Lin, Chun-Jen, Chen, Yu-Wei, Lin, Kuan-Hung, Sung, Pi-Shan, Tang, Chih-Wei, Chu, Hai-Jui, Tsai, Kun-Chang, Chou, Chao-Liang, Lin, Ching-Huang, Wei, Cheng-Yu, Yen, Shang-Yih, Chen, Po-Lin, Yeh, Hsu-Ling, Chan, Lung, Sung, Sheng-Feng, Lee, Meng, Liu, Hon-Man, Lin, Yen-Heng, Lee, I-Hui, Yeh, Shin-Joe, Lien, Li-Ming, Chiou, Hung-Yi, Lee, Jiunn-Tay, Tang, Sung-Chun, Jeng, Jiann-Shing, Tang, Sung-Chun, Jeng, Jiann-Shing, Lee, Chung-Wen, Chen, Chih-Hao, Lin, Yen-Heng, Yeh, Shin-Joe, Lee, Bo-Ching, Chung, Tai-Chun, Lin, Chun-Jen, Lee, I-Hui, Chi, Nai-Fang, Hsu, Li-Chi, Chung, Chih-Ping, Liu, Hung-Yu, Luo, Chao-Bao, Chang, Feng-Chi, Lin, Chung-Jung, Wu, Chia-Hung, Yu, Kai-Wei, Hwang, Hsuen-En, Lin, Te-Ming, Chen, Yu-Wei, Chen, Chi-Jen, Wang, Ching-Yi, Kuo, Yeh-Lin, Lu, Ping-Sheng, Chao, Yen-Tung, Su, Yi-Hsin, Lin, Pei-Ju, Chen, Yi-Chun, Fan, Li-Ling, Yang, Ju-Fang, Lin, Kuan-Hung, Lin, Chien-Jen, Yang, Sheng-Hsiang, Yang, Chun-Ming, Lin, Huey-Juan, Yeh, Poh-Shiow, Chang, Chia-Yu, Cheng, Tian-Junn, Lee, Wei-Jia, Ko, Ching-Chung, Tsui, Yu-Kun, Shih, Yun-Ju, Wu, Te-Chang, Sung, Pi-Shan, Chang Chun-Min Wang, Yu-Ming, Huang, Chih-Yuan, Chen, Chih-Hung, Hsieh, Meng-Tsang, Ou, Chang-Hsien, Lin, Wan-Ching, Chen, Li-Ching, Ann, Bi-Shin, Tang, Chih-Wei, Lai, Yen-Jun, Huang, Lih-Wen, Kuo, Ya-Ling, Peng, Szu-Hsiang, Pai Lin, Yi-Chun, Chu, Hai-Jui, Lin, Cheng-Huai, Sun, Yu, Lu, Chien-Jung, Lee, Chun-Yu, Liu, Chang-Hsiu, Tsai, Kun-Chang, Chen, Kuo-Wei, Tsai, Li-Kai, Hsiue, Yen-Chung, Cheng, Ya-Wen, Fu, Chuan-Hsiu, Chen, Wen-Yu, Chou, Chao-Liang, Po, Helen L., Lin, Ya-Ju, Hwang, Yung-Pin, Kuo, Shu-Fan, Huang, Chun-Chao, Jhou, Zong-Yi, Yu, Hui-Fen, Lin, Hsiao-Chu, Wei, Cheng-Yu, Chen, Chih-Lin, Wu, Pei-han, Tsai, Yi-Ching, Yen, Shang-Yih, Lee, Jiunn-tay, Chou, Chung-Hsing, Ko, Chien-An, Chen, Po-Lin, Tsuei, Yuang-Seng, Chen, Wen-Hsien, Liao, Nien-Chen, Liaw, Yeng-Fung, Yeh, Hsu-Ling, Lien, Li-Ming, Hsiao, Chen-Yu, Lin, Kuan-Yu, Yang, Tsui-Hua, Chan, Lung, Chen, Jia-Hung, Yu, Shun-Fan, Su, I-Chang, Lu, Yueh-Hsun, Sung, Sheng-Feng, Yang, Tzu-Hsien, Hsu, Yung-Chu, Su, Yu-Hsiang, Hung, Ling-Chien, Lin, Mao-Hsun, Su, Chien-Yu, Liu, Hon-Man, Huang, Yung-Chuan, Wan, Chih-Cheng, Lin, Ching-Huang, Yen, Cheng- Chang, Shih, Ching-Sen, Lin, Chun-Shien, Lee, Meng, Tsai, Yuan-Hsiung, Huang, Yen-Chu, Hung, Wei-Tse, and Lee, Jiann-Der

Published
2024
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105. Magnetic resonance imaging for characterization of hepatocellular carcinoma metabolism.

Author

Wang, Lixia, Yang, Ju, Yoo, Charles, Lai, Keane, Braun, Jonathan, McGovern, Dermot, Xie, Yibin, Pandol, Stephen, Lu, Shelly, and Li, Debiao

Subjects
hepatocellular carcinoma, hypoxia, magnetic resonance imaging, metabolism, positron emission tomography/MR, tumor micro environment
Abstract

With a better understanding of the pathophysiological and metabolic changes in hepatocellular carcinoma (HCC), multiparametric and novel functional magnetic resonance (MR) and positron emission tomography (PET) techniques have received wide interest and are increasingly being applied in preclinical and clinical research. These techniques not only allow for non-invasive detection of structural, functional, and metabolic changes in malignant tumor cells but also characterize the tumor microenvironment (TME) and the interactions of malignant tumor cells with the TME, which has hypoxia and low pH, resulting from the Warburg effect and accumulation of metabolites produced by tumor cells and other cellular components. The heterogeneity and complexity of the TME require a combination of images with various parameters and modalities to characterize tumors and guide therapy. This review focuses on the value of multiparametric magnetic resonance imaging and PET/MR in evaluating the structural and functional changes of HCC and in detecting metabolites formed owing to HCC and the TME.

Published
2022

106. Provider Attitudes Toward Risk-Based Hepatocellular Carcinoma Surveillance in Patients With Cirrhosis in the United States.

Author

Kim, Nicole, Rozenberg-Ben-Dror, Karine, Jacob, David, Rich, Nicole, Singal, Amit, Aby, Elizabeth, Yang, Ju, Nguyen, Veronica, Pillai, Anjana, Fuchs, Michael, Moon, Andrew, Shroff, Hersh, Agarwal, Parul, Perumalswami, Ponni, Chandna, Shaun, Zhou, Kali, Patel, Yuval, Latt, Nyan, Wong, Robert, Duarte-Rojo, Andres, Lindenmeyer, Christina, Frenette, Catherine, Ge, Jin, Mehta, Neil, Yao, Francis, Benhammou, Jihane, Bloom, Patricia, Leise, Michael, Kim, Hyun-Seok, Levy, Cynthia, Barnard, Abbey, Khalili, Mandana, and Ioannou, George

Subjects
Computed Tomography, Liver Cancer, Magnetic Resonance Imaging, Screening, Ultrasound, Attitude of Health Personnel, Carcinoma, Hepatocellular, Diagnostic Tests, Routine, Early Detection of Cancer, Humans, Liver Cirrhosis, Liver Neoplasms, Ultrasonography, United States, alpha-Fetoproteins
Abstract

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) surveillance rates are suboptimal in clinical practice. We aimed to elicit providers opinions on the following aspects of HCC surveillance: preferred strategies, barriers and facilitators, and the impact of a patients HCC risk on the choice of surveillance modality. METHODS: We conducted a web-based survey among gastroenterology and hepatology providers (40% faculty physicians, 21% advanced practice providers, 39% fellow-trainees) from 26 US medical centers in 17 states. RESULTS: Of 654 eligible providers, 305 (47%) completed the survey. Nearly all (98.4%) of the providers endorsed semi-annual HCC surveillance in patients with cirrhosis, with 84.2% recommending ultrasound ± alpha fetoprotein (AFP) and 15.4% recommending computed tomography (CT) or magnetic resonance imaging (MRI). Barriers to surveillance included limited HCC treatment options, screening test effectiveness to reduce mortality, access to transportation, and high out-of-pocket costs. Facilitators of surveillance included professional society guidelines. Most providers (72.1%) would perform surveillance even if HCC risk was low (≤0.5% per year), while 98.7% would perform surveillance if HCC risk was ≥1% per year. As a patients HCC risk increased from 1% to 3% to 5% per year, providers reported they would be less likely to order ultrasound ± AFP (83.6% to 68.9% to 57.4%; P < .001) and more likely to order CT or MRI ± AFP (3.9% to 26.2% to 36.1%; P < .001). CONCLUSIONS: Providers recommend HCC surveillance even when HCC risk is much lower than the threshold suggested by professional societies. Many appear receptive to risk-based HCC surveillance strategies that depend on patients estimated HCC risk, instead of our current one-size-fits all strategy.

Published
2022

107. Hepatocellular carcinoma surveillance: current practice and future directions

Author

Ahn, Joseph C, Lee, Yi-Te, Agopian, Vatche G, Zhu, Yazhen, You, Sungyong, Tseng, Hsian-Rong, and Yang, Ju Dong

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Rare Diseases, Hepatitis, Chronic Liver Disease and Cirrhosis, Cancer, Digestive Diseases, Prevention, Liver Disease, Infectious Diseases, Liver Cancer, Detection, screening and diagnosis, 4.1 Discovery and preclinical testing of markers and technologies, Good Health and Well Being, Hepatocellular carcinoma, alpha-fetoprotein, cirrhosis, hepatitis B virus, liquid biopsy, surveillance, under-utilization
Abstract

Hepatocellular carcinoma (HCC) is among the leading causes of cancer incidence and mortality worldwide. Surveillance of individuals with cirrhosis or other conditions that confer a high risk of HCC development is essential for early detection and improved overall survival. Biannual ultrasonography with or without alpha-fetoprotein is widely recommended as the standard method for HCC surveillance, but it has limited sensitivity in early disease and may be inadequate in certain individuals. This review article will provide a comprehensive overview of the current landscape of HCC surveillance, including the rationale and indications for HCC surveillance, standard methods for HCC surveillance, and their strengths/limitations. Alternative surveillance methods such as the role of cross-sectional imaging, emerging circulating biomarkers, as well as the problem of under-utilization of HCC surveillance and surveillance-related harms will also be discussed in this review.

Published
2022

110. The Mortality and Overall Survival Trends of Primary Liver Cancer in the United States

Author

Lee, Yi-Te, Wang, Jasmine J, Luu, Michael, Noureddin, Mazen, Kosari, Kambiz, Agopian, Vatche G, Rich, Nicole E, Lu, Shelly C, Tseng, Hsian-Rong, Nissen, Nicholas N, Singal, Amit G, and Yang, Ju Dong

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Liver Cancer, Rare Diseases, Cancer, Liver Disease, Aging, Digestive Diseases, Good Health and Well Being, Aged, Bile Duct Neoplasms, Bile Ducts, Intrahepatic, Carcinoma, Hepatocellular, Cholangiocarcinoma, Humans, Liver Neoplasms, United States, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

BackgroundRecent trends of hepatocellular carcinoma (HCC) mortality and outcome remain unknown in the United States. We investigated the recent trends of primary liver cancer (excluding intrahepatic cholangiocarcinoma) mortality and HCC stage, treatment, and overall survival (OS) in the United States.MethodsThe National Center for Health Statistics Database was analyzed to investigate the trend of primary liver cancer mortality. We analyzed the Surveillance, Epidemiology, and End Results 18 Database to assess the temporal trend of tumor size, stage, treatment, and OS of HCC. We investigated the association between HCC diagnosis year and OS using Cox regression analysis. All statistical tests were 2-sided.ResultsDuring 2000-2018, liver cancer mortality rates increased until 2013, plateaued during 2013-2016 (annual percent change = 0.1%/y, 95% confidence interval [CI] = -2.1%/y to 2.4%/y, P = .92), and started to decline during 2016-2018 (annual percent change = -1.5%/y, 95% CI = -3.2%/y to 0.2%/y, P = .08). However, mortality continues to increase in American Indian and Alaska Native, individuals aged 65 years or older, and in 33 states. There was a 0.61% (95% CI = 0.53% to 0.69%, P

Published
2021

125. Neoadjuvant sintilimab in combination with concurrent chemoradiotherapy for locally advanced gastric or gastroesophageal junction adenocarcinoma: a single-arm phase 2 trial

Author

Wei, Jia, Lu, Xiaofeng, Liu, Qin, Fu, Yao, Liu, Song, Zhao, Yang, Zhou, Jiawei, Chen, Hui, Wang, Meng, Li, Lin, Yang, Ju, Liu, Fangcen, Zheng, Liming, Yin, Haitao, Yang, Yang, Zhou, Chong, Zeng, Ping, Zhou, Xiaoyu, Ding, Naiqing, Chen, Shiqing, Zhao, Xiaochen, Yan, Jing, Fan, Xiangshan, Guan, Wenxian, and Liu, Baorui

Published
2023
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133. The Impact of Sino-US Trade Frictions on Foreign Trade in the Yangtze River Delta Region

Author

Yang, Ju, Guo, Tinglu, Dou, Runliang, Editor-in-Chief, Liu, Jing, Editor-in-Chief, Khasawneh, Mohammad T., Editor-in-Chief, Balas, Valentina Emilia, Series Editor, Bhowmik, Debashish, Series Editor, Khan, Khalil, Series Editor, Masehian, Ellips, Series Editor, Mohammadi-Ivatloo, Behnam, Series Editor, Nayyar, Anand, Series Editor, Pamucar, Dragan, Series Editor, Shu, Dewu, Series Editor, Qiu, Daowen, editor, Jiao, Yusheng, editor, and Yeoh, William, editor

Published
2023
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142. Liver cancer in 2021: Global burden of disease study

Author

Tan, En Ying, Danpanichkul, Pojsakorn, Yong, Jie Ning, Yu, Zhenning, Tan, Darren Jun Hao, Lim, Wen Hui, Koh, Benjamin, Lim, Ryan Yan Zhe, Tham, Ethan Kai Jun, Mitra, Kartik, Morishita, Asahiro, Hsu, Yao-Chun, Yang, Ju Dong, Takahashi, Hirokazu, Zheng, Ming-Hua, Nakajima, Atsushi, Ng, Cheng Han, Wijarnpreecha, Karn, Muthiah, Mark D., Singal, Amit G., and Huang, Daniel Q.

Published
2024
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143. Covalent Chemistry‐Mediated Multimarker Purification of Circulating Tumor Cells Enables Noninvasive Detection of Molecular Signatures of Hepatocellular Carcinoma

Author

Sun, Na, Lee, Yi‐Te, Kim, Minhyung, Wang, Jasmine J, Zhang, Ceng, Teng, Pai‐Chi, Qi, Dongping, Zhang, Ryan Y, Tran, Benjamin V, Lee, Yue Tung, Ye, Jinglei, Palomique, Juvelyn, Nissen, Nicholas N, Han, Steven‐Huy B, Sadeghi, Saeed, Finn, Richard S, Saab, Sammy, Busuttil, Ronald W, Posadas, Edwin M, Liang, Li, Pei, Renjun, Yang, Ju Dong, You, Sungyong, Agopian, Vatche G, Tseng, Hsian‐Rong, and Zhu, Yazhen

Subjects
Digestive Diseases, Genetics, Prevention, Rare Diseases, Liver Disease, Biotechnology, Cancer, Clinical Research, Liver Cancer, 4.1 Discovery and preclinical testing of markers and technologies, Detection, screening and diagnosis, Good Health and Well Being, circulating tumor cells, click chemistry, hepatocellular carcinoma, nanosubstrate, transcriptome profiling
Abstract

Transcriptomic profiling of tumor tissues introduces a large database, which has led to improvements in the ability of cancer diagnosis, treatment, and prevention. However, performing tumor transcriptomic profiling in the clinical setting is very challenging since the procurement of tumor tissues is inherently limited by invasive sampling procedures. Here, we demonstrated the feasibility of purifying hepatocellular carcinoma (HCC) circulating tumor cells (CTCs) from clinical patient samples with improved molecular integrity using Click Chips in conjunction with a multimarker antibody cocktail. The purified CTCs were then subjected to mRNA profiling by NanoString nCounter platform, targeting 64 HCC-specific genes, which were generated from an integrated data analysis framework with 8 tissue-based prognostic gene signatures from 7 publicly available HCC transcriptomic studies. After bioinformatics analysis and comparison, the HCC CTC-derived gene signatures showed high concordance with HCC tissue-derived gene signatures from TCGA database, suggesting that HCC CTCs purified by Click Chips could enable the translation of HCC tissue molecular profiling into a noninvasive setting.

Published
2021

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