Journal of Liver Cancer

Volume 22(1); March 2022

Editorial

Is multidisciplinary treatment effective for hepatocellular carcinoma with portal vein tumor thrombus?: Won Hyeok Choe; J Liver Cancer. 2022;22(1):1-3. Published online March 31, 2022; DOI: https://doi.org/10.17998/jlc.2022.03.15

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Nomogram for predicting overall survival in patients with large (>5 cm) hepatocellular carcinoma based on real-world practice
Nalee Kim, Jeong Il Yu, Hee Chul Park, Jung Yong Hong, Ho Yeong Lim, Myung Ji Goh, Yong-Han Paik
Journal of Liver Cancer.2023; 23(2): 350. CrossRef

Review Articles

Radioembolization for hepatocellular carcinoma: what clinicians need to know: Jin Woo Choi, Hyo-Cheol Kim; J Liver Cancer. 2022;22(1):4-13. Published online February 23, 2022; DOI: https://doi.org/10.17998/jlc.2022.01.16

5,128 Views
310 Downloads
5 Citations

Abstract PDF

Transarterial radioembolization (TARE) with yttrium 90 (⁹⁰Y) has been used in the management of hepatocellular carcinoma (HCC) for more than 10 years in Korea. There are two types of ⁹⁰Y radioactive microspheres available, namely, glass and resin microspheres, with comparable clinical outcomes. In general, TARE outperforms transarterial chemoembolization regarding post-embolization syndrome, time to progression, tumor downsizing for liver transplantation, and hospitalization stay. Although TARE is commonly recommended for patients with unresectable large HCCs, it can be an alternative to or performed in combination with ablation, surgical resection, and systemic treatment. This review aimed to address ⁹⁰Y radioactive microspheres, patient selection, clinical outcomes, simulation tests, radioembolization procedures, follow-up imaging, and complications.

Citations

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Transarterial chemoembolization as an alternative to radioembolization is associated with earlier tumor recurrence than in radioembolization-eligible patients
Sung Won Chung, Heejin Cho, Hyunjae Shin, Jeayeon Park, Ju Yeon Kim, Ji Hoon Hong, Moon Haeng Hur, Min Kyung Park, Yun Bin Lee, Su Jong Yu, Myungsu Lee, Yoon Jun Kim, Jin Chul Paeng, Jung-Hwan Yoon, Jin Wook Chung, Jeong-Hoon Lee, Hyo-Cheol Kim
Frontiers in Oncology.2023;[Epub] CrossRef
The evolution of immune checkpoint inhibitor combinations in advanced hepatocellular carcinoma – A systematic review
Brandon M. Meyers, Jennifer J. Knox, David M. Liu, Deanna McLeod, Ravi Ramjeesingh, Vincent C. Tam, Howard J. Lim
Cancer Treatment Reviews.2023; 118: 102584. CrossRef
Recent Advances in Image-Guided Locoregional Therapies for Primary Liver Tumors
Cody R. Criss, Mina S. Makary
Biology.2023; 12(7): 999. CrossRef
Multidisciplinary consensus recommendations for management of hepatocellular carcinoma in Middle East and North Africa region
Imam Waked, Sherif Alsammany, Sayed Hammad Tirmazy, Kakil Rasul, Jafar Bani‐Issa, Wael Abdel‐Razek, Ashraf Omar, Amr Shafik, Salem Eid, Amr Abdelaal, Ahmed Hosni, Gamal Esmat
Liver International.2023; 43(10): 2062. CrossRef
Impact of Low Skeletal Muscle Mass on Long-Term Outcomes in Hepatocellular Carcinoma Treated with Trans-Arterial Radioembolization: A Retrospective Multi-Center Study
Heechul Nam, Hyun Yang, Ho Soo Chun, Han Ah Lee, Joon Yeul Nam, Jeong Won Jang, Yeon Seok Seo, Do Young Kim, Yoon Jun Kim, Si Hyun Bae
Cancers.2023; 15(21): 5195. CrossRef

A clinical and pathological update on hepatocellular carcinoma: Salvatore Lorenzo Renne, Luca Di Tommaso; J Liver Cancer. 2022;22(1):14-22. Published online March 31, 2022; DOI: https://doi.org/10.17998/jlc.2022.03.18

6,215 Views
454 Downloads
9 Citations

Abstract PDF

It is estimated that more than 1 million individuals will be affected annually by hepatocellular carcinoma (HCC) by 2025. HCC can be broadly grouped into two major molecular subgroups, each of which is characterized by specific morphological and phenotypic features that mirror the genetic background. The use of these tissue biomarkers in the daily practice of pathologists promises to better allocate patients with HCC with adequate treatments. In turn, this will likely boost the attitude of clinicians toward obtaining a pre-treatment biopsy.

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Identification of gallbladder cancer by direct near-infrared measurement of raw bile combined with two-trace two-dimensional correlation analysis
Eunjin Jang, Woosuk Sohng, Dongho Choi, Hoeil Chung
The Analyst.2023; 148(2): 374. CrossRef
Measurement of Heavy Metal and Antioxidant-Oxidant Levels in Tissues Obtained From Three Different Localizations of Explant Hepatectomy of Patients With Hepatocellular Carcinoma
Cemalettin Koc, Sami Akbulut, Kemal Baris Sarici, Muhammed Mehdi Uremis, Ufuk Gunay Dogan, Zeynep Kucukakcali, Ibrahim Umar Garzali, Ertugrul Karabulut, Yusuf Turkoz, Sezai Yilmaz
Transplantation Proceedings.2023; 55(5): 1262. CrossRef
Adding MRI as a Surveillance Test for Hepatocellular Carcinoma in Patients with Liver Cirrhosis Can Improve Prognosis
Su Jong Yu, Jeong-Ju Yoo, Dong Ho Lee, Su Jin Kim, Eun Ju Cho, Se Hyung Kim, Jeong-Hoon Lee, Yoon Jun Kim, Jeong Min Lee, Jae Young Lee, Jung-Hwan Yoon
Biomedicines.2023; 11(2): 382. CrossRef
Development of a sorafenib-loaded solid self-nanoemulsifying drug delivery system: Formulation optimization and characterization of enhanced properties
Chaemin Lim, Dayoon Lee, Mikyung Kim, Subin Lee, Yuseon Shin, Jacob D. Ramsey, Han-Gon Choi, Eun Seong Lee, Yu Seok Youn, Kyung Taek Oh
Journal of Drug Delivery Science and Technology.2023; 82: 104374. CrossRef
Validation of MELD 3.0 scoring system in East Asian patients with cirrhosis awaiting liver transplantation
Jeong-Ju Yoo, Jong-In Chang, Ji Eun Moon, Dong Hyun Sinn, Sang Gyune Kim, Young Seok Kim
Liver Transplantation.2023; 29(10): 1029. CrossRef
Higher Number of Tumor-Infiltrating PD-L1+ Cells Is Related to Better Response to Multikinase Inhibitors in Hepatocellular Carcinoma
Ji Won Han, Ji Hoon Kim, Dong Hyun Kim, Jeong Won Jang, Si Hyun Bae, Jong Young Choi, Seung Kew Yoon, Jaegyoon Ahn, Hyun Yang, Pil Soo Sung
Diagnostics.2023; 13(8): 1453. CrossRef
Risk of dyslipidemia in chronic hepatitis B patients taking tenofovir alafenamide: a systematic review and meta-analysis
Eui Gwon Hwang, Eun-Ae Jung, Jeong-Ju Yoo, Sang Gyune Kim, Young Seok Kim
Hepatology International.2023; 17(4): 860. CrossRef
Recent application of artificial intelligence on histopathologic image-based prediction of gene mutation in solid cancers
Mohammad Rizwan Alam, Kyung Jin Seo, Jamshid Abdul-Ghafar, Kwangil Yim, Sung Hak Lee, Hyun-Jong Jang, Chan Kwon Jung, Yosep Chong
Briefings in Bioinformatics.2023;[Epub] CrossRef
Role of pelitinib in the regulation of migration and invasion of hepatocellular carcinoma cells via inhibition of Twist1
Sewoong Lee, Eunjeong Kang, Unju Lee, Sayeon Cho
BMC Cancer.2023;[Epub] CrossRef

Recent updates on the classification of hepatoblastoma according to the International Pediatric Liver Tumors Consensus: Se Un Jeong, Hyo Jeong Kang; J Liver Cancer. 2022;22(1):23-29. Published online March 17, 2022; DOI: https://doi.org/10.17998/jlc.2022.02.24

4,080 Views
386 Downloads
2 Citations

Abstract PDF

Hepatoblastoma is the most common pediatric liver malignancy and usually occurs within the first 3 years of life. In recent years, the overall incidence of hepatoblastoma has exhibited the greatest increase among all pediatric malignancies worldwide. The diagnosis of hepatoblastoma may be challenging due to the lack of a current consensus classification system. The International Pediatric Liver Tumors Consensus introduced guidelines and a consensus classification for the diagnosis of hepatoblastoma as either epithelial or mixed epithelial and mesenchymal and in the updated 5^th edition of the World Health Organization Classification of Digestive System Tumors.

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Adult hepatoblastoma: making the challenging distinction from hepatocellular carcinoma
Allison Kaye L. Pagarigan, Paulo Giovanni L. Mendoza
Journal of Liver Cancer.2023; 23(1): 219. CrossRef
Advances in Histological and Molecular Classification of Hepatocellular Carcinoma
Joon Hyuk Choi, Swan N. Thung
Biomedicines.2023; 11(9): 2582. CrossRef

Original Articles

Diagnostic performance of serum exosomal miRNA-720 in hepatocellular carcinoma: Jeong Won Jang, Ji Min Kim, Hye Seon Kim, Jin Seoub Kim, Ji Won Han, Soon Kyu Lee, Heechul Nam, Pil Soo Sung, Si Hyun Bae, Jong Young Choi, Seung Kew Yoon; J Liver Cancer. 2022;22(1):30-39. Published online March 21, 2022; DOI: https://doi.org/10.17998/jlc.2022.02.25

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121 Downloads

Abstract PDF Supplementary Material: Background/Aim
Hepatocellular carcinoma (HCC) is associated with poor prognosis, largely due to late detection. Highly accurate biomarkers are urgently needed to detect early-stage HCC. Our study aims to explore the diagnostic performance of serum exosomal microRNA (miR)-720 in HCC.
Methods
Exosomal miRNA was measured via quantitative real-time PCR. A correlation analysis of exosomal miR-720 and tumor or clinico-demographic data of patients with HCC was performed. The receiver operating characteristic (ROC) curve was used to assess the diagnostic capacity of serum exosomal miR-720 for HCC, in comparison with α-fetoprotein (AFP) and prothrombin induced by vitamin K absence or antagonist-II (PIVKA-II).
Results
MiR-720 was chosen as a potential HCC marker via miR microarray based on significant differential expression between tumor and non-tumor samples. Serum exosomal miR-720 was significantly upregulated in patients with HCC (n=114) versus other liver diseases (control, n=30), with a higher area under the ROC curve (AUC=0.931) than the other markers. Particularly, serum exosomal miR-720 showed superior performance in diagnosing small HCC (< 5 cm; AUC=0.930) compared with AFP (AUC=0.802) or PIVKA-II (AUC=0.718). Exosomal miR-720 levels showed marginal correlation with tumor size. The proportion of elevated miR-720 also increased with intrahepatic tumor stage progression. Unlike AFP or PIVKA-II showing a significant correlation with aminotransferase levels, the exosomal miR-720 level was not affected by aminotransferase levels.
Conclusions
Serum exosomal miR-720 is an excellent biomarker for the diagnosis of HCC, with better performance than AFP or PIVKA-II. Its diagnostic utility is maintained even in small HCC and is unaffected by aminotransferase levels.

The effects of immune checkpoint modulators on the clinical course of patients with resectable hepatocellular carcinoma: Jihyun An, Hyo Jeong Kang, Eunsil Yu, Han Chu Lee, Ju Hyun Shim; J Liver Cancer. 2022;22(1):40-50. Published online March 17, 2022; DOI: https://doi.org/10.17998/jlc.2022.03.06

2,671 Views
108 Downloads

Abstract PDF Supplementary Material: Background/Aim
Immune checkpoint proteins regulating T-cell mediated anti-tumor immunity have been reported to affect clinical outcomes in multiple malignancies. This study aimed to investigate the prognostic effect of histological expression of immune checkpoint proteins in patients with resected hepatocellular carcinoma (HCC).
Methods
A total of 221 patients with HCC who underwent curative resection were included. Expression of programmed-cell death ligand-1 (PD-L1) in tumor cells (tPD-L1) and tumor infiltrating mononuclear cells (TIMCs) (iPD-L1), programmed-cell death-1 in TIMCs (iPD-1), and cytotoxic T lymphocyte antigen-4 in TIMCs (iCTLA-4) were measured immunohistochemically.
Results
Histo-positivity for iCTLA-4, iPD-1, iPD-L1, and tPD-L1 was 32.1%, 42.5%, 35.3%, and 14.9%, respectively. Multivariate logistic analyses revealed that male sex and tumor >5 cm were variables related to iCTLA-4 positivity (odds ratio [OR], 0.46 and 1.94, respectively; P<0.05). Poor differentiation was related to PD-L1 expression in both tumor cells and TIMCs (OR, 2.88 and 3.46, respectively; P<0.05). Microvascular invasion was significantly associated only with iPD-L1 (OR, 2.24; P<0.05). In time-dependent outcome analyses, expression of immune checkpoint proteins in TIMCs (i.e., iCTLA-4, iPD-1, and iPD-L1) was significantly related to longer overall survival and non-cancer-related survival (all P<0.05), but not to time-to-recurrence or cancer-specific deaths. Concurrent activation of the PD-1:PD-L1 and CTLA-4 pathways predicted improved outcomes in terms of overall survival and non-cancer related survival (P=0.06 and P=0.03, respectively).
Conclusions
Immune checkpoint proteins upregulated in TIMCs in HCC tissues have individual and additive effects in prolonging the survival of patients, specifically in terms of survival not related to cancer recurrence.

Case Reports

Complete response to local therapy for advanced hepatocellular carcinoma with lung metastasis: a case report: Daeun Kim, Seiyeon Park, Won Sohn, Hyun Pyo Hong, Byung Ik Kim; J Liver Cancer. 2022;22(1):51-56. Published online January 27, 2022; DOI: https://doi.org/10.17998/jlc.2021.12.28

2,473 Views
86 Downloads

Abstract PDF: The concept of oligometastasis is widely accepted for various types of solid tumors; accordingly, better outcomes can be anticipated with aggressive local interventions. The treatment of advanced hepatocellular carcinoma (HCC) with extrahepatic metastasis is systemic therapy. However, treatment responses to systemic therapy are poor. Recently, a small number of metastatic cancers (oligometastasis) have been controlled by local therapy rather than systemic therapy. Our study reports a case of a 66-year-old male patient with advanced HCC with lung metastasis, which was treated with local therapy. There were less than four metastases in the lungs, which were treated with wedge resection, radiofrequency, and radiation therapy. He repeatedly underwent local therapy for lung oligometastasis and locoregional therapy for intrahepatic HCC rather than systemic therapy; control by local therapy was possible as his liver function was preserved with Child-Turcotte-Pugh class A.

A case report of advanced hepatocellular carcinoma treated with hepatic arterial infusion chemotherapy and sorafenib combination therapy followed by metastasectomy of lung and muscle metastases: Sang Yi Moon, Sang Young Han, Yang-Hyun Baek; J Liver Cancer. 2022;22(1):57-62. Published online January 6, 2022; DOI: https://doi.org/10.17998/jlc.2021.12.20

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Abstract PDF: Currently, various tyrosine kinase inhibitors and immune checkpoint inhibitors have been suggested in the treatment guidelines for advanced hepatocellular carcinoma (HCC). However, sorafenib was the only systemic drug approved 10 years ago. In 2010, a woman diagnosed with HCC rupture and multiple lung metastases visited our hospital. At the time of visiting our hospital, she had undergone transarterial chemoembolization at another hospital to control bleeding due to HCC rupture. We treated her with hepatic arterial infusion chemotherapy and sorafenib combination therapy to increase the control of intrahepatic tumors in consideration of the modest efficacy of sorafenib. The intrahepatic tumor was almost controlled. Metastasectomy was performed to control lung oligometastasis. Subsequently, additional muscle metastasis was confirmed, and metastasectomy was performed. Although this is a very rare case, it shows that a multidisciplinary approach can improve the prognosis of patients with HCC.

Sorafenib combined with radiation therapy for advanced hepatocellular carcinoma with portal and hepatic vein invasion extending to the inferior vena cava: a complete response case according to modified RECIST criteria: Yuri Cho, Bo Hyun Kim, Tae Hyun Kim, Young Hwan Koh, Joong-Won Park; J Liver Cancer. 2022;22(1):63-68. Published online February 14, 2022; DOI: https://doi.org/10.17998/jlc.2022.01.18

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87 Downloads
2 Citations

Abstract PDF

The prognosis of patients with advanced hepatocellular carcinoma (HCC) with tumor thrombus extending to the inferior vena cava (IVC) is extremely poor. Herein, we present a rare case of advanced HCC that was treated with sorafenib and radiotherapy, leading to complete remission. This patient had a 9 cm infiltrative HCC occupying almost the entire left lobe with a tumor thrombus extending through the hepatic vein, IVC, and left portal vein. The patient received 400 mg sorafenib twice daily. One year after the start of sorafenib, intensity-modulated radiation therapy for viable HCC and tumor thrombus was performed with a dose of 5,500 cGy. Twenty-seven months after the starting date of sorafenib, there was no intratumoral arterial enhancement, which suggested a complete response according to the modified RECIST criteria. This case suggests that the combination of sorafenib and radiotherapy might provide clinical benefits in patients with advanced HCC with IVC tumor thrombus.

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Feasibility of additional radiotherapy in patients with advanced hepatocellular carcinoma treated with atezolizumab plus bevacizumab
Tae Hyun Kim, Bo Hyun Kim, Yu Ri Cho, Young-Hwan Koh, Joong-Won Park
Journal of Liver Cancer.2023; 23(2): 330. CrossRef
Is multidisciplinary treatment effective for hepatocellular carcinoma with portal vein tumor thrombus?
Won Hyeok Choe
Journal of Liver Cancer.2022; 22(1): 1. CrossRef

Concurrent transarterial radioembolization and combination atezolizumab/ bevacizumab treatment of infiltrative hepatocellular carcinoma with portal vein tumor thrombosis: a case report: Min Kyung Park, Su Jong Yu; J Liver Cancer. 2022;22(1):69-74. Published online March 21, 2022; DOI: https://doi.org/10.17998/jlc.2022.03.09

2,757 Views
96 Downloads
3 Citations

Abstract PDF

Treatment options for advanced hepatocellular carcinoma (HCC) have been rapidly evolving. Herein, we describe a patient with advanced HCC and portal vein tumor thrombosis (PVTT) who responded decisively to a multidisciplinary approach. The patient had an ill-defined infiltrative HCC (diffuse subtype), with several intrahepatic metastasis and tumor invasion of left portal vein. Concurrent use of transarterial radioembolization (TARE) and systemic therapeutics (atezolizumab + bevacizumab) ultimately proved successful. There was marked reduction in tumor volume after TARE and an additional three cycles of atezolizumab plus bevacizumab. This concurrent treatment was well tolerated, without adverse events during immunotherapy. The impressive results achieved suggest that concurrent TARE and combination atezolizumab/bevacizumab is a promising treatment approach for advanced HCC with PVTT.

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Combining immunotherapy with transarterial radioembolization
ZeynepCeren Balaban Genc, Efe Soydemır, SevalAy Ersoy, Tunc Ones
Indian Journal of Nuclear Medicine.2023; 38(2): 145. CrossRef
The New Era of Systemic Treatment for Hepatocellular Carcinoma: From the First Line to the Optimal Sequence
Maria Cerreto, Ferdinando Cardone, Lucia Cerrito, Leonardo Stella, Francesco Santopaolo, Maria Pallozzi, Antonio Gasbarrini, Francesca Romana Ponziani
Current Oncology.2023; 30(10): 8774. CrossRef
Is multidisciplinary treatment effective for hepatocellular carcinoma with portal vein tumor thrombus?
Won Hyeok Choe
Journal of Liver Cancer.2022; 22(1): 1. CrossRef

Multidisciplinary treatment with immune checkpoint inhibitors for advanced stage hepatocellular carcinoma: Ahlim Lee, Jaejun Lee, Hyun Yang, Soo-Yoon Sung, Chang Ho Jeon, Su Ho Kim, Moon Hyung Choi, Young Joon Lee, Ho Jong Chun, Si Hyun Bae; J Liver Cancer. 2022;22(1):75-83. Published online March 18, 2022; DOI: https://doi.org/10.17998/jlc.2022.03.04

3,084 Views
83 Downloads
2 Citations

Abstract PDF

Hepatocellular carcinoma (HCC) is a cytotoxic chemotherapy-resistant tumor and most HCCs arise in a background of liver cirrhosis of various causes. Although the IMBrave150 trial showed remarkable advancements in the treatment of unresectable HCC with atezolizumab plus bevacizumab (AteBeva), therapeutic outcomes were unsatisfactory in more than half of the patients. Accordingly, many ongoing trials combine conventional modalities with new drugs such as immune checkpoint inhibitors for better treatment outcomes, and they are expected to benefit patients with limited responses to conventional treatment. Here, two patients with advanced stage HCC with preserved liver function and good performance status showed partial response after treatment with combination or sequential therapy of AteBeva, hepatic arterial infusion chemotherapy, radiation therapy, and transarterial chemoembolization. These findings indicate the efficacy of multidisciplinary treatment against advanced HCC. Additional studies are required to establish optimal treatment strategies.

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Citations to this article as recorded by

Feasibility of additional radiotherapy in patients with advanced hepatocellular carcinoma treated with atezolizumab plus bevacizumab
Tae Hyun Kim, Bo Hyun Kim, Yu Ri Cho, Young-Hwan Koh, Joong-Won Park
Journal of Liver Cancer.2023; 23(2): 330. CrossRef
Is multidisciplinary treatment effective for hepatocellular carcinoma with portal vein tumor thrombus?
Won Hyeok Choe
Journal of Liver Cancer.2022; 22(1): 1. CrossRef

Long-term survival after CCRT and HAIC followed by ALPPS for hepatocellular carcinoma with portal vein invasion: a case report: In-Jung Kim, Sung Hwan Yoo, Jung Il Lee, Kwan Sik Lee, Hyun Woong Lee, Jin Hong Lim; J Liver Cancer. 2022;22(1):84-90. Published online March 22, 2022; DOI: https://doi.org/10.17998/jlc.2022.03.07

2,160 Views
66 Downloads
1 Citation

Abstract PDF

There are various methods for treating advanced hepatocellular carcinoma with portal vein invasion, such as systemic chemotherapy, transarterial chemoembolization, transarterial radioembolization, and concurrent chemoradiotherapy. These methods have similar clinical efficacy but are designed with a palliative aim. Herein, we report a case that experienced complete remission through “associating liver partition and portal vein ligation for staged hepatectomy (ALPPS)” after concurrent chemoradiotherapy and hepatic artery infusion chemotherapy. In this patient, concurrent chemoradiotherapy and hepatic artery infusion chemotherapy induced substantial tumor shrinkage, and hypertrophy of the nontumor liver was sufficiently induced by portal vein ligation (stage 1 surgery) followed by curative resection (stage 2 surgery). Using this approach, long-term survival with no evidence of recurrence was achieved at 16 months. Therefore, the optimal use of ALPPS requires sufficient consideration in cases of significant hepatocellular carcinoma shrinkage for curative purposes.

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Is multidisciplinary treatment effective for hepatocellular carcinoma with portal vein tumor thrombus?
Won Hyeok Choe
Journal of Liver Cancer.2022; 22(1): 1. CrossRef

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