Journal of Liver Cancer

Volume 23(1); March 2023

Guideline

2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma: J Liver Cancer. 2023;23(1):1-120. Published online December 9, 2022; DOI: https://doi.org/10.17998/jlc.2022.11.07

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Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the fourth most common cancer among men in South Korea, where the prevalence of chronic hepatitis B infection is high in middle and old age. The current practice guidelines will provide useful and sensible advice for the clinical management of patients with HCC. A total of 49 experts in the fields of hepatology, oncology, surgery, radiology, and radiation oncology from the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2018 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions. These guidelines provide useful information and direction for all clinicians, trainees, and researchers in the diagnosis and treatment of HCC.

Citations

Citations to this article as recorded by

Diagnostic performance of the 2022 KLCA-NCC criteria for hepatocellular carcinoma on magnetic resonance imaging with extracellular contrast and hepatobiliary agents: comparison with the 2018 KLCA-NCC criteria
Ja Kyung Yoon, Sunyoung Lee, Jeong Ah Hwang, Ji Eun Lee, Seung-seob Kim, Myeong-Jin Kim
Journal of Liver Cancer.2023; 23(1): 157. CrossRef
Radiologic features of hepatocellular carcinoma related to prognosis
Shin Hye Hwang, Hyungjin Rhee
Journal of Liver Cancer.2023; 23(1): 143. CrossRef
Current status of ultrasonography in national cancer surveillance program for hepatocellular carcinoma in South Korea: a large-scale multicenter study
Sun Hong Yoo, Soon Sun Kim, Sang Gyune Kim, Jung Hyun Kwon, Han-Ah Lee, Yeon Seok Seo, Young Kul Jung, Hyung Joon Yim, Do Seon Song, Seong Hee Kang, Moon Young Kim, Young-Hwan Ahn, Jieun Han, Young Seok Kim, Young Chang, Soung Won Jeong, Jae Young Jang, J
Journal of Liver Cancer.2023; 23(1): 189. CrossRef
Smoking Increases the Risk of Hepatocellular Carcinoma and Cardiovascular Disease in Patients with Metabolic-Associated Fatty Liver Disease
Jeong-Ju Yoo, Man Young Park, Eun Ju Cho, Su Jong Yu, Sang Gyune Kim, Yoon Jun Kim, Young Seok Kim, Jung-Hwan Yoon
Journal of Clinical Medicine.2023; 12(9): 3336. CrossRef

Editorials

How to optimize the treatment strategy for advanced-stage hepatocellular carcinoma with macrovascular invasion: Beom Kyung Kim; J Liver Cancer. 2023;23(1):121-123. Published online March 24, 2023; DOI: https://doi.org/10.17998/jlc.2023.3.10

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Impact of the updated KLCA-NCC criteria for diagnosis of “probable HCC” in liver MRI: comparisons between KLCA v2022 and v2018: Jeong Hee Yoon; J Liver Cancer. 2023;23(1):124-126. Published online March 21, 2023; DOI: https://doi.org/10.17998/jlc.2023.3.7

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Review Articles

Non-alcoholic fatty liver disease-related hepatocellular carcinoma: Darine Daher, Karim Seif El Dahan, Amit G. Singal; J Liver Cancer. 2023;23(1):127-142. Published online February 9, 2023; DOI: https://doi.org/10.17998/jlc.2022.12.30

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2 Citations

Abstract PDF

Non-alcoholic fatty liver disease (NAFLD), one of the most common causes of liver disease, is an increasingly common cause of hepatocellular carcinoma (HCC). Several demographic, clinical, and genetic factors contribute to HCC risk in NAFLD patients, which may inform risk stratification scores. Proven efficacious approaches to primary prevention approach in patients with non-viral liver disease remain an area of need. Semi-annual surveillance is associated with improved early tumor detection and reduced HCC-related mortality; however, patients with NAFLD have several challenges to effective surveillance, including under-recognition of at-risk patients, low surveillance utilization in clinical practice, and lower sensitivity of current tools for early-stage HCC detection. Treatment decisions are best made in a multidisciplinary fashion and are informed by several factors including tumor burden, liver dysfunction, performance status, and patient preferences. Although patients with NAFLD often have larger tumor burden and increased comorbidities compared to counterparts, they can achieve similar post-treatment survival with careful patient selection. Therefore, surgical therapies continue to provide a curative treatment option for patients diagnosed at an early stage. Although there has been debate about the efficacy of immune checkpoint inhibitors in patients with NAFLD, current data are insufficient to change treatment selection based on liver disease etiology.

Citations

Citations to this article as recorded by

Smoking Increases the Risk of Hepatocellular Carcinoma and Cardiovascular Disease in Patients with Metabolic-Associated Fatty Liver Disease
Jeong-Ju Yoo, Man Young Park, Eun Ju Cho, Su Jong Yu, Sang Gyune Kim, Yoon Jun Kim, Young Seok Kim, Jung-Hwan Yoon
Journal of Clinical Medicine.2023; 12(9): 3336. CrossRef
Reply: Validation of MELD 3.0 scoring system in East Asian patients with cirrhosis awaiting liver transplantation
Jeong-Ju Yoo, Sang Gyune Kim
Liver Transplantation.2023;[Epub] CrossRef

Radiologic features of hepatocellular carcinoma related to prognosis: Shin Hye Hwang, Hyungjin Rhee; J Liver Cancer. 2023;23(1):143-156. Published online March 9, 2023; DOI: https://doi.org/10.17998/jlc.2023.02.16

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Abstract PDF: The cross-sectional imaging findings play a crucial role in the diagnosis of hepatocellular carcinoma (HCC). Recent studies have shown that imaging findings of HCC are not only relevant for the diagnosis of HCC, but also for identifying genetic and pathologic characteristics and determining prognosis. Imaging findings such as rim arterial phase hyperenhancement, arterial phase peritumoral hyperenhancement, hepatobiliary phase peritumoral hypointensity, non-smooth tumor margin, low apparent diffusion coefficient, and the LR-M category of the Liver Imaging-Reporting and Data System have been reported to be associated with poor prognosis. In contrast, imaging findings such as enhancing capsule appearance, hepatobiliary phase hyperintensity, and fat in mass have been reported to be associated with a favorable prognosis. Most of these imaging findings were examined in retrospective, single-center studies that were not adequately validated. However, the imaging findings can be applied for deciding the treatment strategy for HCC, if their significance can be confirmed by a large multicenter study. In this literature, we would like to review imaging findings related to the prognosis of HCC as well as their associated clinicopathological characteristics.

Original Articles

Diagnostic performance of the 2022 KLCA-NCC criteria for hepatocellular carcinoma on magnetic resonance imaging with extracellular contrast and hepatobiliary agents: comparison with the 2018 KLCA-NCC criteria: Ja Kyung Yoon, Sunyoung Lee, Jeong Ah Hwang, Ji Eun Lee, Seung-seob Kim, Myeong-Jin Kim; J Liver Cancer. 2023;23(1):157-165. Published online February 23, 2023; DOI: https://doi.org/10.17998/jlc.2023.02.07

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1 Citation

Abstract PDF Supplementary Material

Background/Aim
This study aimed to determine the diagnostic performance of 2022 Korean Liver Cancer Association-National Cancer Center (KLCA-NCC) imaging criteria compared with the 2018 KLCA-NCC for hepatocellular carcinoma (HCC) in high-risk patients using magnetic resonance imaging (MRI).
Methods
This retrospective study included 415 treatment-naïve patients (152 patients who underwent extracellular contrast agent [ECA]-MRI and 263 who underwent hepatobiliary agent [HBA]-MRI; 535 lesions, including 412 HCCs) with a high risk of HCC who underwent contrast-enhanced MRI. Two readers evaluated all lesions according to the 2018 and 2022 KLCA-NCC imaging diagnostic criteria, and the per-lesion diagnostic performances were compared.
Results
In “definite” HCC category of both 2018 and 2022 KLCA-NCC, HBA-MRI showed a significantly higher sensitivity for the diagnosis of HCC than ECA-MRI (77.0% vs. 64.3%, P=0.006) without a significant difference in specificity (94.7% vs. 95.7%, P=0.801). On ECAMRI, “definite” or “probable” HCC categories of the 2022 KLCA-NCC had significantly higher sensitivity than those of the 2018 KLCA-NCC (85.3% vs. 78.3%, P=0.002) with identical specificity (93.6%). On HBA-MRI, the sensitivity and specificity of “definite” or “probable” HCC categories of both 2018 and 2022 KLCA-NCC were not significantly different (83.3% vs. 83.6%, P>0.999 and 92.1% vs. 90.8%, P>0.999, respectively).
Conclusions
In “definite” HCC category of both 2018 and 2022 KLCA-NCC, HBA-MRI provides better sensitivity than ECA-MRI without compromising specificity. On ECA-MRI, “definite” or “probable” HCC categories of the 2022 KLCA-NCC may improve sensitivity in the diagnosis of HCC compared with the 2018 KLCA-NCC.

Citations

Citations to this article as recorded by

Impact of the updated KLCA-NCC criteria for diagnosis of “probable HCC” in liver MRI: comparisons between KLCA v2022 and v2018
Jeong Hee Yoon
Journal of Liver Cancer.2023; 23(1): 124. CrossRef

Use of doxorubicin-eluting bead transarterial chemoembolization for unresectable hepatocellular carcinoma with portal vein invasion: a prospective study: Su Jong Yu, Yun Bin Lee, Eun Ju Cho, Jeong-Hoon Lee, Hyo-Cheol Kim, Jin Wook Chung, Jung-Hwan Yoon, Yoon Jun Kim; J Liver Cancer. 2023;23(1):166-176. Published online March 3, 2023; DOI: https://doi.org/10.17998/jlc.2023.02.08

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Abstract PDF Supplementary Material: Background/Aim
To evaluate the applicability of transarterial chemoembolization (TACE) treatment with doxorubicin drug-eluting beads (DEBs) in advanced hepatocellular carcinoma (HCC) patients with portal vein invasion (PVI).
Methods
This prospective study was approved by the institutional review board and informed consent was obtained from all participants. A total of 30 HCC patients with PVI received DEB-TACE between 2015 and 2018. The following parameters were evaluated: complications during DEB-TACE, abdominal pain, fever, and laboratory outcomes, including liver function change. Overall survival (OS), time to progression (TTP), and adverse events were also analyzed and assessed.
Results
DEBs measuring 100–300 μm in diameter were loaded with doxorubicin (150 mg per procedure). There were no complications during DEB-TACE and no significant differences in the levels of prothrombin time, serum albumin, or total bilirubin at follow-up compared to baseline. The median TTP was 102 days (95% confidence interval [CI], 42–207 days) and the median OS was 216 days (95% CI, 160–336 days). Three patients (10%) had severe adverse reactions, including transient acute cholangitis (n=1), cerebellar infarction (n=1), and pulmonary embolism (n=1), but no treatment-related death occurred.
Conclusions
DEB-TACE may be a therapeutic option for advanced HCC patients with PVI.

Subclassification of advanced-stage hepatocellular carcinoma with macrovascular invasion: combined transarterial chemoembolization and radiotherapy as an alternative first-line treatment: Sujin Jin, Won-Mook Choi, Ju Hyun Shim, Danbi Lee, Kang Mo Kim, Young-Suk Lim, Han Chu Lee, Jinhong Jung, Sang Min Yoon, Jonggi Choi; J Liver Cancer. 2023;23(1):177-188. Published online March 23, 2023; DOI: https://doi.org/10.17998/jlc.2023.03.04

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1 Citation

Abstract PDF Supplementary Material

Background/Aim
The Barcelona Clinic Liver Cancer (BCLC) guidelines recommend systemic therapy as the only first-line treatment for patients with BCLC stage C hepatocellular carcinoma (HCC) despite its heterogeneity of disease extent. We aimed to identify patients who might benefit from combined transarterial chemoembolization (TACE) and radiation therapy (RT) by subclassifying BCLC stage C.
Methods
A total of 1,419 treatment-naïve BCLC stage C patients with macrovascular invasion (MVI) who were treated with combined TACE and RT (n=1,115) or systemic treatment (n=304) were analyzed. The primary outcome was overall survival (OS). Factors associated with OS were identified and assigned points by the Cox model. The patients were subclassified into three groups based on these points.
Results
The mean age was 55.4 years, and 87.8% were male. The median OS was 8.3 months. Multivariate analysis revealed a significant association of Child-Pugh B, infiltrative-type tumor or tumor size ≥10 cm, main or bilateral portal vein invasion, and extrahepatic metastasis with poor OS. The sub-classification was categorized into low (point ≤1), intermediate (point=2), and high (point ≥3) risks based on the sum of points (range, 0–4). The OS in the low, intermediate, and high-risk groups was 22.6, 8.2, and 3.8 months, respectively. In the low and intermediate-risk groups, patients treated with combined TACE and RT exhibited significantly longer OS (24.2 and 9.5 months, respectively) than those who received systemic treatment (6.4 and 5.1 months, respectively; P<0.0001).
Conclusions
Combined TACE and RT may be considered as a first-line treatment option for HCC patients with MVI when classified into low- and intermediate-risk groups.

Citations

Citations to this article as recorded by

How to optimize the treatment strategy for advanced-stage hepatocellular carcinoma with macrovascular invasion
Beom Kyung Kim
Journal of Liver Cancer.2023; 23(1): 121. CrossRef

Current status of ultrasonography in national cancer surveillance program for hepatocellular carcinoma in South Korea: a large-scale multicenter study: Sun Hong Yoo, Soon Sun Kim, Sang Gyune Kim, Jung Hyun Kwon, Han-Ah Lee, Yeon Seok Seo, Young Kul Jung, Hyung Joon Yim, Do Seon Song, Seong Hee Kang, Moon Young Kim, Young-Hwan Ahn, Jieun Han, Young Seok Kim, Young Chang, Soung Won Jeong, Jae Young Jang, Jeong-Ju Yoo; J Liver Cancer. 2023;23(1):189-201. Published online March 24, 2023; DOI: https://doi.org/10.17998/jlc.2023.03.11

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Abstract PDF Supplementary Material: Background/Aim
Abdominal ultrasonography (USG) is recommended as a surveillance test for high-risk groups for hepatocellular carcinoma (HCC). This study aimed to analyze the current status of the national cancer surveillance program for HCC in South Korea and investigate the effects of patient-, physician-, and machine-related factors on HCC detection sensitivity.
Methods
This multicenter retrospective cohort study collected surveillance USG data from the high-risk group for HCC (liver cirrhosis or chronic hepatitis B or C >40 years of age) at eight South Korean tertiary hospitals in 2017.
Results
In 2017, 45 experienced hepatologists or radiologists performed 8,512 USG examinations. The physicians had a mean 15.0±8.3 years of experience; more hepatologists (61.4%) than radiologists (38.6%) participated. Each USG scan took a mean 12.2±3.4 minutes. The HCC detection rate by surveillance USG was 0.3% (n=23). Over 27 months of follow-up, an additional 135 patients (0.7%) developed new HCC. The patients were classified into three groups based on timing of HCC diagnosis since the 1st surveillance USG, and no significant intergroup difference in HCC characteristics was noted. HCC detection was significantly associated with patient-related factors, such as old age and advanced fibrosis, but not with physician- or machine-related factors.
Conclusions
This is the first study of the current status of USG as a surveillance method for HCC at tertiary hospitals in South Korea. It is necessary to develop quality indicators and quality assessment procedures for USG to improve the detection rate of HCC.

Case Reports

Parenchymal-sparing hepatectomy for multiple bilobar colorectal liver metastases in a Jehovah’s witness: a case report: Shehan Ratnayake, Duminda Subasinghe, Vihara Dassanayake, Sivasuriya Sivaganesh; J Liver Cancer. 2023;23(1):202-205. Published online February 15, 2023; DOI: https://doi.org/10.17998/jlc.2023.01.27

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Abstract PDF: Parenchymal-sparing hepatectomy (PSH), though technically challenging, is emerging as a choice of treatment for colorectal liver metastases (CRLM). PSH in Jehovah’s witness (JW) patients, for whom transfusion is not an option, involves complex surgical and medicolegal issues. A 52-year-old JW male with synchronous, multiple, bilobar liver metastases from a rectal adenocarcinoma was referred following neoadjuvant chemotherapy. At surgery, 10 metastatic deposits were observed and confirmed by intraoperative ultrasonography. Parenchymal-sparing non-anatomical resections were performed using a cavitron ultrasonic aspirator with the application of intermittent Pringle maneuvres. Histology confirmed multiple CRLMs with tumor-free resection margins. PSH is increasingly employed for CRLMs to preserve residual liver volume and minimize morbidity without compromising oncological outcomes. It is technically challenging, especially in the presence of bilobar, multi-segmental disease. This case illustrates the feasibility of performing complex hepatic surgery in special patient groups by meticulous planning and preparation involving multiple specialties and the patient.

A case of successful surgical treatment for peritoneal seeding of hepatocellular carcinoma after radiotherapy and atezolizumab plus bevacizumab combination treatment: Yuri Cho, Bo Hyun Kim, Tae Hyun Kim, Young Hwan Koh, Joong-Won Park; J Liver Cancer. 2023;23(1):206-212. Published online February 24, 2023; DOI: https://doi.org/10.17998/jlc.2023.02.09

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1 Citation

Abstract PDF

Peritoneal seeding of hepatocellular carcinoma (HCC) is incurable and has poor prognosis. A 68-year-old man underwent surgical resection for a 3.5 cm single nodular HCC at the tip of segment 3 and transarterial chemoembolization for a 1.5 cm-sized recurrent HCC at the tip of segment 6. 3 months later, an increasing 1 cm pelvic nodule on the rectovesical pouch warranted radiotherapy. Although it stabilized, a new 2.7 cm-sized peritoneal nodule in the right upper quadrant (RUQ) omentum appeared 3.5 years after radiotherapy. Hence, omental mass and small bowel mesentery mass excision were performed. 3 years later, recurrent peritoneal metastases in the RUQ omentum and rectovesical pouch progressed. 33 cycles of atezolizumab and bevacizumab treatment elicited stable disease response. Finally, laparoscopic left pelvic peritonectomy was performed without tumor recurrence. Herein, we present a case of HCC with peritoneal seeding that was successfully treated with surgery after radiotherapy and systemic therapy, leading to complete remission.

Citations

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;[Epub] CrossRef

A case of nearly complete response in hepatocellular carcinoma with disseminated lung metastasis by combination therapy of nivolumab and ipilimumab after treatment failure of atezolizumab plus bevacizumab: Hyung Jun Kim, Sang Youn Hwang, Jung Woo Im, Ki Jeong Jeon, Wan Jeon; J Liver Cancer. 2023;23(1):213-218. Published online March 9, 2023; DOI: https://doi.org/10.17998/jlc.2023.02.23

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Abstract PDF: Recently, the efficacy of immuno-oncologic agents for advanced hepatocellular carcinoma (HCC) has been proven in several trials. In particular, atezolizumab with bevacizumab (AteBeva), as a first-line therapy for advanced HCC, has shown tremendous advances in the IMBrave150 study. However, second or third-line therapy after treatment failure with AteBeva has not been firmly established. Moreover, clinicians have continued their attempts at multidisciplinary treatment that includes other systemic therapy and radiotherapy (RT). Here, we report a case that showed a near complete response (CR) of lung metastasis to nivolumab with ipilimumab therapy after achieving a near CR of intrahepatic tumor using sorafenib and RT in a patient with advanced HCC who had experienced treatment failure of AteBeva.

Adult hepatoblastoma: making the challenging distinction from hepatocellular carcinoma: Allison Kaye L. Pagarigan, Paulo Giovanni L. Mendoza; J Liver Cancer. 2023;23(1):219-224. Published online March 13, 2023; DOI: https://doi.org/10.17998/jlc.2023.02.24

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17 Downloads

Abstract PDF: Hepatoblastoma is an exceptionally rare malignancy in adults with just over 70 non-pediatric cases reported in literature. Recounted is a case of a 49-year-old female who presented with acute right upper quadrant abdominal pain, elevated serum alpha fetoprotein and a large liver mass on imaging. Hepatectomy was performed under clinical suspicion of hepatocellular carcinoma. Immunomorphologic characteristics of the tumor proved consistent with hepatoblastoma of mixed epithelial and mesenchymal type. Hepatocellular carcinoma remains to be the primary differential diagnosis for adult hepatoblastoma, however, distinguishing between these two neoplasms requires close histomorphologic assessment and immunohistochemical profiling as clinical, radiologic and gross pathologic findings typically overlap. Making this distinction is highly crucial in the timely initiation of surgical and chemotherapeutic interventions for this inherently aggressive and rapidly fatal disease.

Favorable response of hepatocellular carcinoma with portal vein tumor thrombosis after radiotherapy combined with atezolizumab plus bevacizumab: Yong Tae Kim, Jina Kim, Jinsil Seong; J Liver Cancer. 2023;23(1):225-229. Published online March 16, 2023; DOI: https://doi.org/10.17998/jlc.2023.02.27

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Abstract PDF: Recently, the superiority of atezolizumab plus bevacizumab (AteBeva) over sorafenib was proven in the IMbrave150 trial, and AteBeva became the first-line systemic treatment for untreated, unresectable hepatocellular carcinoma (HCC). While the results are encouraging, more than half of patients with advanced HCC are still being treated in a palliative setting. Radiotherapy (RT) is known to induce immunogenic effects that may enhance the therapeutic efficacy of immune checkpoint inhibitors. Herein, we report the case of a patient with advanced HCC with massive portal vein tumor thrombosis treated with a combination of RT and AteBeva, who showed near complete response in tumor thrombosis and favorable response to HCC. Although this is a rare case, it shows the importance of reducing the tumor burden via RT to combination immunotherapy in patients with advanced HCC.

The development of hepatocellular carcinoma during long-term treatment for recurrent non-small cell lung cancer: a case report: Seong Kyun Na, Seong Hee Kang; J Liver Cancer. 2023;23(1):230-234. Published online March 27, 2023; DOI: https://doi.org/10.17998/jlc.2023.03.03

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Abstract PDF: Multiple primary malignancies (MPMs) are defined as the presence of two or more malignancies in different organs, without a subordinate relationship. Although rarely reported, hepatocellular carcinoma (HCC) occasionally presents with simultaneous or metachronous primary malignancies in other organs. In this report, we describe a patient with lung adenocarcinoma and lymph node and bone metastases, treated with five chemotherapeutic regimens for 24 months. Changing the chemotherapy regimen based on the suspicion of metastasis of a new liver mass did not lead to improvements. This prompted a liver biopsy and a revised diagnosis of HCC. Sixth-line treatment with the concurrent use of cisplatin-paclitaxel for lung cancer and sorafenib for HCC, stabilized the disease. The concurrent treatment was not tolerated and was discontinued owing to adverse events. Considering our findings, treatment with increased efficacy and lower toxicity for MPMs is warranted.

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