Cancer Research and Treatment

Original Articles

Pediatric cancer

Malignant Hepatocellular Neoplasm, Not Otherwise Specified, Displays Poorer Chemoresponsiveness and Postoperative Prognosis Than Hepatoblastoma: In Hye Song, Sujin Gang, Hee Mang Yoon, Pyeong Hwa Kim, Bokyung Ahn, Jihun Kim, Deok Hoon Kim, Jung-Man Namgoong, Kyung-Nam Koh; Cancer Res Treat. 2026;58(2):642-655. Published online May 12, 2025; DOI: https://doi.org/10.4143/crt.2025.117

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Purpose
Malignant hepatocellular neoplasm, not otherwise specified (HCN-NOS) is a provisional diagnostic entity, characterised by intermediate or a combination of hepatoblastoma and pediatric hepatocellular carcinoma (p-HCC) features. We compared the characteristics of HCN-NOS with hepatoblastoma and p-HCC.
Materials and Methods
The records of 148 pediatric patients diagnosed with hepatocellular malignancy after resection were retrieved from the institutional database. Clinical parameters and histopathology slides were reviewed to re-establish each patient’s diagnosis. Molecular analyses were conducted in 37 patients.
Results
Patients were profiled as 21 (14.2%) with HCN-NOS, 109 (73.6%) with hepatoblastoma, and 18 (12.2%) with p-HCC. The median age was 8.6 years in HCN-NOS, 1.2 years in hepatoblastoma, and 7.9 years in p-HCC. Background liver disease was frequently observed in p-HCC (11/18, 61%) but infrequent in HCN-NOS (4/21, 19%) and hepatoblastoma (4/109, 3.7%). HCN-NOS presented with a more advanced PRETEXT stage (p=0.012), metastasis (p < 0.001), and lymphovascular invasion (p < 0.001) than hepatoblastoma and p-HCC. Patients with HCN-NOS received longer cycles of preoperative chemotherapy; however, they reported a lower decrease in serum alpha-fetoprotein and tumor size than hepatoblastoma (p=0.043, p=0.004, and p=0.044, respectively). HCN-NOS was an independent poor prognostic factor for event-free survival (hazard ratio, 4.968; 95% confidence interval, 2.004 to 12.32; p < 0.001).
Conclusion
The possibility of HCN-NOS should be considered in pediatric patients with liver cancer, especially those ≥ 5 years old with no background liver disease. Because HCN-NOS exhibits poor chemoresponsiveness and unfavourable postoperative prognosis, liver transplantation should be strongly considered.

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Conversion Hepatectomy After New FP Therapy for Malignant Hepatocellular Neoplasm, Not Otherwise Specified: A Case Report
Etsuko Moriyama, Hironori Koga, Takashi Niizeki, Hideki Iwamoto, Shigeo Shimose, Tomotake Shirono, Takahiko Tokushige, Masahito Nakano, Ryoko Kuromatsu, Toru Goto, Masaki Honda, Taizo Hibi, Yoshiki Mikami, Reiichiro Kondo, Jun Akiba, Takumi Kawaguchi
Hepatology Research.2026; 56(6): 1047. CrossRef

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Prognostic Value of POST-Treatment Extent of Tumor (POSTTEXT) System in Patients with Hepatoblastoma: Hana Jeong, Hee Mang Yoon, Pyeong Hwa Kim, Ah Young Jung, Young Ah Cho, Jin Seong Lee, Kyung-Nam Koh, Jung-Man Namgoong; Cancer Res Treat. 2025;57(4):1198-1206. Published online January 20, 2025; DOI: https://doi.org/10.4143/crt.2024.600

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Purpose
This study aimed to assess prognostic values of the POST-Treatment Extent of tumor (POSTTEXT) system and clinical factors after neoadjuvant chemotherapy in hepatoblastoma patients and evaluate benefits of post-treatment imaging and clinical factors concomitant with Children’s Hepatic Tumors International Collaboration–Hepatoblastoma Stratification (CHIC-HS) system.
Materials and Methods
This single-center retrospective study of hepatoblastoma cases (2006-2022) included pediatric patients receiving ≥ 4 cycles of neoadjuvant chemotherapy, with pre- and post-treatment imaging and complete medical records. Clinical data included age, sex, and serum α-fetoprotein (AFP) levels. Cox regression analyses identified predictors of event-free survival (EFS). Time-dependent receiver operating characteristic curves assessed the predictive power of combining the CHIC-HS risk stratification with post-treatment factors. Inter-reader agreement was analyzed using weighted kappa.
Results
Among the 109 hepatoblastoma patients, 73 (mean age, 2.2±2.7 years) met the inclusion criteria. Prognostic factors for EFS included AFP levels after the fourth cycle of neoadjuvant chemotherapy (hazard ratio [HR], 1.233; 95% confidence interval [CI], 1.086 to 1.400; p=0.001), tumor size change ratio (HR, 0.654; 95% CI, 0.448 to 0.955; p=0.030), and POSTTEXT annotation factor M (HR, 5.209; 95% CI, 1.639 to 16.553; p=0.005). Incorporating AFP levels after the fourth cycle of neoadjuvant chemotherapy into the CHIC-HS improved predictive power (p=0.043). POSTTEXT system showed better inter-reader agreement than PRE-Treatment Extent of tumor (PRETEXT).
Conclusion
Predictors of EFS in hepatoblastoma include AFP levels after the fourth cycle of neoadjuvant chemotherapy, tumor size change ratio, and metastasis (POSTTEXT M). Combining AFP levels after the fourth cycle of neoadjuvant chemotherapy to the CHIC-HS improved the predictive ability.

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Surgical management of biliary fistula following associating liver partition and portal vein ligation for staged hepatectomy in pediatric hepatoblastoma: a case report and literature review
Gang Shen, Yunpeng Zhai, Huashan Zhao, Rui Guo, Hongxiu Xu, Sai Huang, Shisong Zhang
Frontiers in Oncology.2025;[Epub] CrossRef

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Children’s Hepatic Tumors International Collaboration-Hepatoblastoma Stratification (CHIC-HS) System for Pediatric Patients with Hepatoblastoma: A Retrospective, Hospital-Based Cohort Study in South Korea: Pyeong Hwa Kim, Hyun Joo Shin, Hee Mang Yoon, Young Hun Choi, Jung-Man Namgoong, Dae Yeon Kim, Kyung-Nam Koh, Mi-Jung Lee, Haesung Yoon, Chuhl Joo Lyu, Jung Woo Han, Seung Min Hahn, Young Ah Cho; Cancer Res Treat. 2022;54(1):253-258. Published online March 24, 2021; DOI: https://doi.org/10.4143/crt.2021.265

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Purpose
In 2017, the Children’s Hepatic Tumors International Collaboration-Hepatoblastoma Stratification (CHIC-HS) system was introduced. We aimed to evaluate the accuracy of CHIC-HS System for the prediction of event-free survival (EFS) in Korean pediatric patients with hepatoblastoma.
Materials and Methods
This two-center retrospective study included consecutive Korean pediatric patients with histopathologically confirmed hepatoblastoma from March 1988 through September 2019. We compared EFS among four risk groups according to the CHIC-HS system. Discriminatory ability of CHIC-HS system was also evaluated using optimism-corrected C-statistics. Factors associated with EFS were explored using multivariable Cox regression analysis.
Results
We included 129 patients (mean age, 2.6±3.3 years; female:male, 63:66). The 5-year EFS rates in the very low, low, intermediate, and high-risk groups, according to the CHIC-HS system were 90.0%, 82.8%, 73.5%, and 51.3%, respectively. The CHIC-HS system aligned significantly well with EFS outcomes (p=0.004). The optimism-corrected C index of CHIC-HS was 0.644 (95% confidence interval [CI], 0.561 to 0.727). Age ≥ 8 (vs. age ≤ 2; hazard ratio [HR], 2.781; 95% CI, 1.187 to 6.512; p=0.018), PRE-Treatment EXTent of tumor (PRETEXT) stage IV (vs. PRETEXT I or II; HR, 2.774; 95% CI, 1.228 to 5.974; p=0.009), and presence of metastasis (HR, 2.886; 95% CI, 1.457 to 5.719; p=0.002), which are incorporated as the first three nodes in the CHIC-HS system, were independently associated with EFS.
Conclusion
The CHIC-HS system aligned significantly well with EFS outcomes in Korean pediatric patients with hepatoblastoma. Age group, PRETEXT stage, and presence of metastasis were independently associated with EFS.

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Prognostic prediction of hepatoblastoma in children: development and validation of machine learning models—an SEER-based study
Jianfeng Luo, Kaikun Huang, Le Zheng, Long Li
Updates in Surgery.2026; 78(5): 2093. CrossRef
Biallelic ARID1A Alterations
Kalyani R. Patel, Martin Urbicain, Stephen F. Sarabia, Cintia R. Perez, Angela M. Major, Kevin E. Fisher, Angshumoy Roy, Frederic Askin, Andras Heczey, Andres F. Espinoza, Sanjeev A. Vasudevan, Pavel Sumazin, Dolores H. Lopez-Terrada
American Journal of Surgical Pathology.2026; 50(9): 1106. CrossRef
The importance of age as a prognostic predictor of childhood hepatoblastoma: an analysis of single-center childhood hepatoblastoma in China
Zhen Li, Hong Jiang, Yuan-Qi Wang, Wen-Qing Wang, Li-Bin Huang, Jun-Cheng Liu, Hong-Man Xue
BMC Pediatrics.2025;[Epub] CrossRef
Prognostic Value of POST-Treatment Extent of Tumor (POSTTEXT) System in Patients with Hepatoblastoma
Hana Jeong, Hee Mang Yoon, Pyeong Hwa Kim, Ah Young Jung, Young Ah Cho, Jin Seong Lee, Kyung-Nam Koh, Jung-Man Namgoong
Cancer Research and Treatment.2025; 57(4): 1198. CrossRef
Elevated serum uric acid is associated with the risk of advanced staging and vascular involvement in patients with hepatoblastoma: a 14-year retrospective study
Yunlan Zhou, Jinning Li, Yanhui Ma, Mengjie Tang, Xiaojun Yuan, Lisong Shen
Frontiers in Oncology.2023;[Epub] CrossRef

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The Broad Variability in Dental Age Observed among Childhood Survivors Is Cancer Specific: Patrycja Proc, Joanna Szczepańska, Małgorzata Zubowska, Beata Zalewska-Szewczyk, Wojciech Młynarski; Cancer Res Treat. 2021;53(1):252-260. Published online August 24, 2020; DOI: https://doi.org/10.4143/crt.2020.275

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Purpose
The study aimed to assess the differences in dental maturation between childhood cancer survivors and healthy children.
Materials and Methods
Fifty-nine cancer patients including 16 (27.1%) girls and 43 (72.8%) boys, aged between 4 and 16 years, underwent dental and radiographic examinations. The mean duration of anticancer therapy was 16.8 months (range, 1 to 47 months), and 4.6 years (range, 8 to 123 months) had passed since the termination of disease. The control group consisted of 177 panoramic radiographs of age- and sex-matched healthy individuals. Dental age (DA) was estimated with Demirjian’s scale and delta age, i.e., DA–chronological age (CA), was used to compare groups.
Results
The DA of cancer survivors was accelerated by almost 1 year compared to their CA (9.9±3.1 vs. 8.9±2.8, p=0.040). The greatest difference was observed among patients with brain tumor: delta (DA–CA) was 2.2±1.1 years. Among all cancer patients, only children with familial adenomatous polyposis (FAP)-associated hepatoblastoma (HP) demonstrated delayed DA, with regard to both other cancer survivors (p=0.011) and healthy patients (p=0.037). All four patients with HP suffered from FAP, and three of them had documented adenomatous polyposis coli (APC) genes mutation. The DA of cancer patients having teeth with short roots was significantly greater than that of the cancer survivors without this anomaly (12.8±3.2 vs. 9.0±2.4, p < 0.001).
Conclusion
DA in children may be altered by cancer disease.

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Dental management of long-term childhood cancer survivors: a systematic review
K. Seremidi, S. Gizani, G. Dahllöf, M. Barr-Agholme, D. Kloukos, G. Tsilingaridis
European Archives of Paediatric Dentistry.2024; 25(5): 611. CrossRef
Dental age estimation in children that have undergone antineoplastic treatment
A. Mitsea, K. Seremidi, A. Tsiligianni, S. Gizani
European Archives of Paediatric Dentistry.2022; 23(2): 243. CrossRef
Comparative Study of Malocclusions between Cancer Patients and Healthy Peers
Patrycja Proc, Joanna Szczepanska, Anna Herud, Malgorzata Zubowska, Wojciech Fendler, Monika Lukomska-Szymanska, Wojciech Mlynarski
International Journal of Environmental Research and Public Health.2022; 19(7): 4045. CrossRef

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Expression and Intracellular Localization of Hepatitis C Viral Core Protein in Human Hepatoma Cell Line Transfected with Viral cDNA: Dong Wan Kim, Sun Hee Kim; J Korean Cancer Assoc. 1997;29(1):11-18.

Abstract PDF: PURPOSE
Establishment of the human liver cell lines which permanently express the HCV proteins is important for the large scale production of viral antigen and analysis of the mechanism of hepatocellular carcinogenesis by HCV. Here, we attempted to establish the human hepatoblastoma cell lines which stably express the HCV core protein and examined the intracellular localization of the core protein.
MATERIALS AND METHODS
The cDNA of HCV core protein and neomycin resistance gene were expressed in HepG2 cells by the SRalpha promoter and human EF-1alpha gene promoter, respectively. The core protein was detected by immunofluorescence assay and western blotting.
RESULTS
We obtained several HepG2 cell clones which express HCV core protein stably. In transient expression assay, the core protein was localized in the cytoplasm in about 90%, and localized in the nucleus in about 10% of the core-expressing HepG2 cells. But, in the stably expressing HepG2 cell clones, the core protein was localized only in the cytoplasm. No HepG2 cell containing core protein in the nucleus was found in all of the cells which stably express the core protein.
CONCLUSION
The EF-1alpha gene promoter is highly efficient in the colony formation by neomycin resistance gene and is very useful for the isolation of human liver cell clones which express foreign genes stably. HCV core protein is localized in both nuclear and cytoplasm of human liver cell in short term but the cells containing the core protein in nucleus seem to disappear in long term culture.

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