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Original Articles
Novel Bronchoscopy Method for Molecular Profiling of Lung Cancer: Targeted Washing Technique
Mi-Hyun Kim, Hayoung Seong, Hyojin Jang, Saerom Kim, Wanho Yoo, Soo Han Kim, Jeongha Mok, Kwangha Lee, Ki Uk Kim, Min Ki Lee, Jung Seop Eom
Received November 25, 2024  Accepted February 25, 2025  Published online February 26, 2025  
DOI: https://doi.org/10.4143/crt.2024.1128    [Accepted]
AbstractAbstract PDF
Purpose
There have been efforts to find alternative samples other than standard samples of tissue or plasma for mutational analyses for lung cancer patients. However, no other sample or technique has replaced the mutational analyses using standard samples. In this prospective study, we assessed a novel bronchoscopy method, named as targeted washing technique, for detecting the EGFR mutation.
Materials and Methods
A 3.0-mm ultrathin bronchoscope was precisely navigated to the target lung lesion with the assistance of virtual bronchoscopic navigation and fluoroscopy. Once the bronchoscope is placed in front of target lung lesion, 0.9% normal saline was instilled for targeted washing. EGFR testing using targeted washing fluid (TWF) was compared to standard methods using plasma or tumor tissue.
Results
In 41 TWF samples, the T790M mutation was detected in tissue, plasma, and TWF samples at rates of 22%, 10%, and 29%, respectively. The overall EGFR T790M detection rate using tissue, plasma, or TWF samples was 37%, with TWF samples increasing the T790M mutation detection rate by up to 10%. The accuracy of T790M mutation detection using TWF sample was 83% compared with standard samples. Four patients were found to have the EGFR T790M mutation solely through EGFR testing using TWF, which repeated rebiopsies using either plasma or tissue finally confirmed to have the T790M mutation.
Conclusion
We demonstrated the clinical potential of targeted washing technique for molecular testing, which can be a good option to overcome spatial heterogeneity, low sensitivity of plasma sample or technical limitations in collecting tumor tissues.
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Breast cancer
Molecular Classification of Breast Cancer Using Weakly Supervised Learning
Wooyoung Jang, Jonghyun Lee, Kyong Hwa Park, Aeree Kim, Sung Hak Lee, Sangjeong Ahn
Cancer Res Treat. 2025;57(1):116-125.   Published online June 25, 2024
DOI: https://doi.org/10.4143/crt.2024.113
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The molecular classification of breast cancer is crucial for effective treatment. The emergence of digital pathology has ushered in a new era in which weakly supervised learning leveraging whole-slide images has gained prominence in developing deep learning models because this approach alleviates the need for extensive manual annotation. Weakly supervised learning was employed to classify the molecular subtypes of breast cancer.
Materials and Methods
Our approach capitalizes on two whole-slide image datasets: one consisting of breast cancer cases from the Korea University Guro Hospital (KG) and the other originating from The Cancer Genomic Atlas dataset (TCGA). Furthermore, we visualized the inferred results using an attention-based heat map and reviewed the histomorphological features of the most attentive patches.
Results
The KG+TCGA-trained model achieved an area under the receiver operating characteristics value of 0.749. An inherent challenge lies in the imbalance among subtypes. Additionally, discrepancies between the two datasets resulted in different molecular subtype proportions. To mitigate this imbalance, we merged the two datasets, and the resulting model exhibited improved performance. The attentive patches correlated well with widely recognized histomorphologic features. The triple-negative subtype has a high incidence of high-grade nuclei, tumor necrosis, and intratumoral tumor-infiltrating lymphocytes. The luminal A subtype showed a high incidence of collagen fibers.
Conclusion
The artificial intelligence (AI) model based on weakly supervised learning showed promising performance. A review of the most attentive patches provided insights into the predictions of the AI model. AI models can become invaluable screening tools that reduce costs and workloads in practice.
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General
Clinicopathological Characteristics of NRG1 Fusion–Positive Solid Tumors in Korean Patients
Yoon Jin Cha, Chung Lee, Bio Joo, Kyung A Kim, Choong-kun Lee, Hyo Sup Shim
Cancer Res Treat. 2023;55(4):1087-1095.   Published online June 15, 2023
DOI: https://doi.org/10.4143/crt.2023.682
AbstractAbstract PDFPubReaderePub
Purpose
Neuregulin 1 (NRG1) gene fusion is a potentially actionable oncogenic driver. The oncoprotein binds to ERBB3-ERBB2 heterodimers and activates downstream signaling, supporting a therapeutic approach for inhibiting ERBB3/ERBB2. However, the frequency and clinicopathological features of solid tumors harboring NRG1 fusions in Korean patients remain largely unknown.
Materials and Methods
We reviewed archival data from next-generation sequencing panel tests conducted at a single institution, specifically selecting patients with in-frame fusions that preserved the functional domain. The clinicopathological characteristics of patients harboring NRG1 fusions were retrospectively reviewed.
Results
Out of 8,148 patients, NRG1 fusions were identified in 22 patients (0.27%). The average age of the patients was 59 years (range, 32 to 78 years), and the male-to-female ratio was 1:1.2. The lung was the most frequently observed primary site (n=13), followed by the pancreaticobiliary tract (n=3), gastrointestinal tract (n=2, stomach and rectum each), ovary (n=2), breast (n=1), and soft tissue (n=1). Histologically, all tumors demonstrated adenocarcinoma histology, with the exception of one case of sarcoma. CD74 (n=8) and SLC3A2 (n=4) were the most frequently identified fusion partners. Dominant features included the presence of fewer than three co-occurring genetic alterations, a low tumor mutation burden, and low programmed death-ligand 1 expression. Various clinical responses were observed in patients with NRG1 fusions.
Conclusion
Despite the rarity of NRG1 fusions in Korean patients with solid tumors, identification through next-generation sequencing enables the possibility of new targeted therapies.

Citations

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  • Continuous multimodal data supply chain and expandable clinical decision support for oncology
    Jee Suk Chang, Hyunwook Kim, Eun Sil Baek, Jeong Eun Choi, Joon Seok Lim, Jin Sung Kim, Sang Joon Shin
    npj Digital Medicine.2025;[Epub]     CrossRef
  • Expert Consensus on the Diagnosis and Treatment of NRG1/2 Gene Fusion Solid Tumors
    Chunwei Xu, Qian Wang, Dong Wang, Wenxian Wang, Wenfeng Fang, Ziming Li, Aijun Liu, Jinpu Yu, Wenzhao Zhong, Zhijie Wang, Yongchang Zhang, Jingjing Liu, Shirong Zhang, Xiuyu Cai, Anwen Liu, Wen Li, Ping Zhan, Hongbing Liu, Tangfeng Lv, Liyun Miao, Lingfen
    Global Medical Genetics.2024; 11(01): 086.     CrossRef
  • Analysis on the pathogenesis and treatment progress of NRG1 fusion-positive non-small cell lung cancer
    Hongyan Li, Lina Xu, Hongshun Cao, Tianyi Wang, Siwen Yang, Yixin Tong, Linlin Wang, Qiang Liu
    Frontiers in Oncology.2024;[Epub]     CrossRef
  • Analysis of CD74 Occurrence in Oncogenic Fusion Proteins
    Jasmine Vargas, Georgios Pantouris
    International Journal of Molecular Sciences.2023; 24(21): 15981.     CrossRef
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Comparison of the Data of a Next-Generation Sequencing Panel from K-MASTER Project with That of Orthogonal Methods for Detecting Targetable Genetic Alterations
Yoon Ji Choi, Jung Yoon Choi, Ju Won Kim, Ah Reum Lim, Youngwoo Lee, Won Jin Chang, Soohyeon Lee, Jae Sook Sung, Hee-Joon Chung, Jong Won Lee, Eun Joo Kang, Jung Sun Kim, Taekyu Lim, Hye Sook Kim, Yu Jung Kim, Mi Sun Ahn, Young Saing Kim, Ji Hyun Park, Seungtaek Lim, Sung Shim Cho, Jang Ho Cho, Sang Won Shin, Kyong Hwa Park, Yeul Hong Kim
Cancer Res Treat. 2022;54(1):30-39.   Published online May 20, 2021
DOI: https://doi.org/10.4143/crt.2021.218
AbstractAbstract PDFPubReaderePub
Purpose
K-MASTER project is a Korean national precision medicine platform that screened actionable mutations by analyzing next-generation sequencing (NGS) of solid tumor patients. We compared gene analyses between NGS panel from the K-MASTER project and orthogonal methods.
Materials and Methods
Colorectal, breast, non–small cell lung, and gastric cancer patients were included. We compared NGS results from K-MASTER projects with those of non-NGS orthogonal methods (KRAS, NRAS, and BRAF mutations in colorectal cancer [CRC]; epidermal growth factor receptor [EGFR], anaplastic lymphoma kinase [ALK] fusion, and reactive oxygen species 1 [ROS1] fusion in non–small cell lung cancer [NSCLC], and Erb-B2 receptor tyrosine kinase 2 (ERBB2) positivity in breast and gastric cancers).
Results
In the CRC cohort (n=225), the sensitivity and specificity of NGS were 87.4% and 79.3% (KRAS); 88.9% and 98.9% (NRAS); and 77.8% and 100.0% (BRAF), respectively. In the NSCLC cohort (n=109), the sensitivity and specificity of NGS for EGFR were 86.2% and 97.5%, respectively. The concordance rate for ALK fusion was 100%, but ROS1 fusion was positive in only one of three cases that were positive in orthogonal tests. In the breast cancer cohort (n=260), ERBB2 amplification was detected in 45 by NGS. Compared with orthogonal methods that integrated immunohistochemistry and in situ hybridization, sensitivity and specificity were 53.7% and 99.4%, respectively. In the gastric cancer cohort (n=64), ERBB2 amplification was detected in six by NGS. Compared with orthogonal methods, sensitivity and specificity were 62.5% and 98.2%, respectively.
Conclusion
The results of the K-MASTER NGS panel and orthogonal methods showed a different degree of agreement for each genetic alteration, but generally showed a high agreement rate.

Citations

Citations to this article as recorded by  
  • Genomic Profiling of Driver Gene Alterations in Patients With Non–Small Cell Lung Cancer, Patterns of Treatment and Impact on Survival Outcomes: A Single Center Experience of More Than 1200 Patients
    Minit Shah, Vanita Noronha, Vijay Patil, Ajay Kumar Singh, Nandini Menon, Supriya Goud, Srushti Shah, Sucheta More, Akhil Kapoor, Bal Krishna Mishra, Pratik Chandrani, Anuradha Chougule, Vinod Gupta, Priyanka Pange, Omshree Shetty, Trupti Pai, Rajiv Kaush
    Clinical Lung Cancer.2025;[Epub]     CrossRef
  • Integrated clinical and genomic models using machine-learning methods to predict the efficacy of paclitaxel-based chemotherapy in patients with advanced gastric cancer
    Yonghwa Choi, Jangwoo Lee, Keewon Shin, Ji Won Lee, Ju Won Kim, Soohyeon Lee, Yoon Ji Choi, Kyong Hwa Park, Jwa Hoon Kim
    BMC Cancer.2024;[Epub]     CrossRef
  • Supporting Biomarker-Driven Therapies in Oncology: A Genomic Testing Cost Calculator
    Albrecht Stenzinger, Brian Cuffel, Noman Paracha, Eric Vail, Jesus Garcia-Foncillas, Clifford Goodman, Ulrik Lassen, Gilles Vassal, Sean D Sullivan
    The Oncologist.2023; 28(5): e242.     CrossRef
  • Genomic analysis of plasma circulating tumor DNA in patients with heavily pretreated HER2 + metastatic breast cancer
    Kyoungmin Lee, Jongwon Lee, Jungmin Choi, Sung Hoon Sim, Jeong Eun Kim, Min Hwan Kim, Yeon Hee Park, Jee Hyun Kim, Su-Jin Koh, Kyong Hwa Park, Myoung Joo Kang, Mi Sun Ahn, Kyoung Eun Lee, Hee-Jun Kim, Hee Kyung Ahn, Han Jo Kim, Keon Uk Park, In Hae Park
    Scientific Reports.2023;[Epub]     CrossRef
  • Recommendations for the Use of Next-Generation Sequencing and the Molecular Tumor Board for Patients with Advanced Cancer: A Report from KSMO and KCSG Precision Medicine Networking Group
    Shinkyo Yoon, Miso Kim, Yong Sang Hong, Han Sang Kim, Seung Tae Kim, Jihun Kim, Hongseok Yun, Changhoon Yoo, Hee Kyung Ahn, Hyo Song Kim, In Hee Lee, In-Ho Kim, Inkeun Park, Jae Ho Jeong, Jaekyung Cheon, Jin Won Kim, Jina Yun, Sun Min Lim, Yongjun Cha, Se
    Cancer Research and Treatment.2022; 54(1): 1.     CrossRef
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Carcinoembryonic Antigen Improves the Performance of Magnetic Resonance Imaging in the Prediction of Pathologic Response after Neoadjuvant Chemoradiation for Patients with Rectal Cancer
Gyu Sang Yoo, Hee Chul Park, Jeong Il Yu, Doo Ho Choi, Won Kyung Cho, Young Suk Park, Joon Oh Park, Ho Yeong Lim, Won Ki Kang, Woo Yong Lee, Hee Cheol Kim, Seong Hyeon Yun, Yong Beom Cho, Yoon Ah Park, Kyoung Doo Song, Seok-Hyung Kim, Sang Yun Ha
Cancer Res Treat. 2020;52(2):446-454.   Published online September 25, 2019
DOI: https://doi.org/10.4143/crt.2019.261
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The purpose of this study was to investigate the role of carcinoembryonic antigen (CEA) levels in improving the performance of magnetic resonance imaging (MRI) for the prediction of pathologic response after the neoadjuvant chemoradiation (NCRT) for patients with rectal cancer.
Materials and Methods
We retrospectively reviewed the medical records of 524 rectal cancer patients who underwent NCRT and total mesorectal excision between January 2009 and December 2014. The performances of MRI with or without CEA parameters (initial CEA and CEA dynamics) for prediction of pathologic tumor response grade (pTRG) were compared by receiver-operating characteristic analysis with DeLong’s method. Cox regression was used to identify the independent factors associated to pTRG and disease-free survival (DFS) after NCRT.
Results
The median follow-up was 64.0 months (range, 3.0 to 113.0 months). On multivariate analysis, poor tumor regression grade on MRI (mrTRG; p < 0.001), initial CEA (p < 0.001) and the mesorectal fascia involvement on MRI before NCRT (mrMFI; p=0.054) showed association with poor pTRG. The mrTRG plus CEA parameters showed significantly improved performances in the prediction of pTRG than mrTRG alone. All of mrTRG, mrMFI, and initial CEA were also identified as independent factors associated with DFS. The initial CEA further discriminated DFS in the subgroups with good mrTRG or that without mrMFI.
Conclusion
The CEA parameters significantly improved the performance of MRI in the prediction of pTRG after NCRT for patients with rectal cancer. The DFS was further discriminated by initial CEA level in the groups with favorable MRI parameters.

Citations

Citations to this article as recorded by  
  • Clinical outcomes of neoadjuvant chemoradiotherapy followed by total mesorectal excision in locally advanced rectal cancer with mesorectal fascia involvement
    Jeong Ha Lee, Nalee Kim, Jeong Il Yu, Gyu Sang Yoo, Hee Chul Park, Woo-Yong Lee, Seong Hyeon Yun, Hee Cheol Kim, Yong Beom Cho, Jung Wook Huh, Yoon Ah Park, Jung Kyong Shin, Joon Oh Park, Seung Tae Kim, Young Suk Park, Jeeyun Lee, Won Ki Kang
    Radiation Oncology Journal.2024; 42(2): 130.     CrossRef
  • Predicting the response to neoadjuvant chemoradiation for rectal cancer using nomograms based on MRI tumour regression grade
    S. Qin, Y. Chen, K. Liu, Y. Li, Y. Zhou, W. Zhao, P. Xin, Q. Wang, S. Lu, H. Wang, N. Lang
    Cancer/Radiothérapie.2024; 28(4): 341.     CrossRef
  • Body composition parameters combined with blood biomarkers and magnetic resonance imaging predict responses to neoadjuvant chemoradiotherapy in locally advanced rectal cancer
    Jianguo Yang, Qican Deng, Zhenzhou Chen, Yajun Chen, Zhongxue Fu
    Frontiers in Oncology.2023;[Epub]     CrossRef
  • Pretreatment blood biomarkers combined with magnetic resonance imaging predict responses to neoadjuvant chemoradiotherapy in locally advanced rectal cancer
    Xinyu Shi, Min Zhao, Bo Shi, Guoliang Chen, Huihui Yao, Junjie Chen, Daiwei Wan, Wen Gu, Songbing He
    Frontiers in Oncology.2022;[Epub]     CrossRef
  • Clinical implication and management of rectal cancer with clinically suspicious lateral pelvic lymph node metastasis: A radiation oncologist’s perspective
    Gyu Sang Yoo, Hee Chul Park, Jeong Il Yu
    Frontiers in Oncology.2022;[Epub]     CrossRef
  • High-Resolution T2-Weighted MRI to Evaluate Rectal Cancer: Why Variations Matter
    Kirsten L Gormly
    Korean Journal of Radiology.2021; 22(9): 1475.     CrossRef
  • MRI Assessment of Complete Response to Preoperative Chemoradiation Therapy for Rectal Cancer: 2020 Guide for Practice from the Korean Society of Abdominal Radiology
    Seong Ho Park, Seung Hyun Cho, Sang Hyun Choi, Jong Keon Jang, Min Ju Kim, Seung Ho Kim, Joon Seok Lim, Sung Kyoung Moon, Ji Hoon Park, Nieun Seo
    Korean Journal of Radiology.2020; 21(7): 812.     CrossRef
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  • 183 Download
  • 7 Web of Science
  • 7 Crossref
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Selection Criteria for Active Surveillance of Patients with Prostate Cancer in Korea: A Multicenter Analysis of Pathology after Radical Prostatectomy
Chang Wook Jeong, Sung Kyu Hong, Seok Soo Byun, Seong Soo Jeon, Seong Il Seo, Hyun Moo Lee, Hanjong Ahn, Dong Deuk Kwon, Hong Koo Ha, Tae Gyun Kwon, Jae Seung Chung, Cheol Kwak, Hyung Jin Kim
Cancer Res Treat. 2018;50(1):265-274.   Published online April 14, 2017
DOI: https://doi.org/10.4143/crt.2016.477
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Korean patients with prostate cancer (PC) typically present with a more aggressive disease than patients in Western populations. Consequently, it is unclear if the current criteria for active surveillance (AS) can safely be applied to Korean patients. Therefore, this study was conducted to define appropriate selection criteria for AS for patients with PC in Korea.
Materials and Methods
We conducted a multicenter retrospective study of 2,126 patients with low risk PC who actually underwent radical prostatectomy. The primary outcome was an unfavorable disease, which was defined by non-organ confined disease or an upgrading of the Gleason score to ≥ 7 (4+3). Predictive variables of an unfavorable outcome were identified by multivariate analysis using randomly selected training samples (n=1,623, 76.3%). We compared our selected criteria to various Western criteria for the primary outcome and validated our criteria using the remaining validation sample (n=503, 23.7%).
Results
A non-organ confined disease rate of 14.9% was identified, with an increase in Gleason score ≥ 7 (4+3) of 8.7% and a final unfavorable disease status of 20.8%. The following criteria were selected: Gleason score ≤ 6, clinical stage T1-T2a, prostate-specific antigen (PSA) ≤ 10 ng/mL, PSA density < 0.15 ng/mL/mL, number of positive cores ≤ 2, and maximum cancer involvement in any one core ≤ 20%. These criteria provided the lowest unfavorable disease rate (11.7%) when compared to Western criteria (13.3%-20.7%), and their validity was confirmed using the validation sample (5.9%).
Conclusion
We developed AS criteria which are appropriate for Korean patients with PC. Prospective studies using these criteria are now warranted.

Citations

Citations to this article as recorded by  
  • Has Active Surveillance for Prostate Cancer Become Safer? Lessons Learned from a Global Clinical Registry
    Chris Bangma, Paul Doan, Lin Zhu, Sebastiaan Remmers, Daan Nieboer, Jozien Helleman, Monique J. Roobol, Mikio Sugimoto, Byung Ha Chung, Lui Shiong Lee, Mark Frydenberg, Laurence Klotz, Michael Peacock, Antoinette Perry, Anders Bjartell, Antti Rannikko, Mi
    European Urology Oncology.2025; 8(2): 324.     CrossRef
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    Takuma Kato, Ryuji Matsumoto, Akira Yokomizo, Yoichiro Tohi, Hiroshi Fukuhara, Yoichi Fujii, Keiichiro Mori, Takuma Sato, Junichi Inokuchi, Katsuyoshi Hashine, Shinichi Sakamoto, Hidefumi Kinoshita, Koji Inoue, Toshiki Tanikawa, Takanobu Utsumi, Takayuki
    BJU International.2024; 134(4): 652.     CrossRef
  • Establishment of Prospective Registry of Active Surveillance for Prostate Cancer: The Korean Urological Oncology Society Database
    Gyoohwan Jung, Jung Kwon Kim, Seong Soo Jeon, Jae Hoon Chung, Cheol Kwak, Chang Wook Jeong, Hanjong Ahn, Jae Young Joung, Tae Gyun Kwon, Sung Woo Park, Seok-Soo Byun
    The World Journal of Men's Health.2023; 41(1): 110.     CrossRef
  • The Role of Magnetic Resonance Imaging (MRI) and MRI-Targeted Biopsy for Active Surveillance
    Chang Wook Jeong
    Journal of Urologic Oncology.2023; 21(2): 97.     CrossRef
  • Incidence and mortality projections for major cancers among Korean men until 2034, with a focus on prostate cancer
    Sahyun Pak, Kyu-Won Jung, Eun-Hye Park, Young Hwii Ko, Young-Joo Won, Jae Young Joung
    Investigative and Clinical Urology.2022; 63(2): 175.     CrossRef
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    Yasmine Amrousy, Hesham Haffez, Doaa Abdou, Hanaa Atya
    Molecular Medicine Reports.2022;[Epub]     CrossRef
  • A single-center long-term experience of active surveillance for prostate cancer: 15 years of follow-up
    Sang Hun Song, Jung Kwon Kim, Hakmin Lee, Sangchul Lee, Sung Kyu Hong, Seok-Soo Byun
    Investigative and Clinical Urology.2021; 62(1): 32.     CrossRef
  • The clinical impact of strict criteria for active surveillance of prostate cancer in Korean population: Results from a prospective cohort
    Jungyo Suh, Hyeong Dong Yuk, Minyong Kang, Bum Sik Tae, Ja Hyeon Ku, Hyeon Hoe Kim, Cheol Kwak, Chang Wook Jeong
    Investigative and Clinical Urology.2021; 62(4): 430.     CrossRef
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    Kerri Beckmann, Aida Santaolalla, Jozien Helleman, Peter Carroll, Byung Ha Chung, Lui Shiong Lee, Antoinette Perry, Jose Rubio-Briones, Mikio Sugimoto, Bruce Trock, Riccardo Valdagni, Prokar Dasgupta, Mieke Van Hemelrijck, Oussama Elhage, Bruce Trock, Beh
    European Urology Open Science.2021; 34: 47.     CrossRef
  • Patients with Biopsy Gleason Score 3 + 4 Are Not Appropriate Candidates for Active Surveillance
    Juhyun Park, Sangjun Yoo, Min Chul Cho, Chang Wook Jeong, Ja Hyeon Ku, Cheol Kwak, Hyeon Hoe Kim, Hyeon Jeong
    Urologia Internationalis.2020; 104(3-4): 199.     CrossRef
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    Takumi Shiraishi, Osamu Ukimura
    Current Opinion in Urology.2018; 28(6): 529.     CrossRef
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    Kun Liu, Shuo Gu, Xuzhong Liu, Qing Sun, Yunyan Wang, Junsong Meng, Zongyuan Xu
    Oncotarget.2017; 8(42): 72933.     CrossRef
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Gastroenteropancreatic Neuroendocrine Tumors with Liver Metastases in Korea: A Clinicopathological Analysis of 72 Cases in a Single Institute
Yooju Shin, Sang Yun Ha, Jiyeon Hyeon, Boram Lee, Jeeyun Lee, Kee-Taek Jang, Kyoung-Mee Kim, Young Suk Park, Cheol-Keun Park
Cancer Res Treat. 2015;47(4):738-746.   Published online February 16, 2015
DOI: https://doi.org/10.4143/crt.2014.224
AbstractAbstract PDFPubReaderePub
Purpose
Management of gastroenteropancreatic (GEP) neuroendocrine tumors with liver metastases (NETLM) presents many clinical challenges. Assessment of the extent of disease and primary tumor site is crucial for management. In this study, we investigated the primary tumor sites and prognostic factors in GEP NETLM among Korean patients. Materials and Methods We reviewed the medical records of 72 Korean patients diagnosed with GEP NETLM between January 1999 and May 2013, focusing on their clinical and pathologic characteristics.
Results
The most frequently encountered primary tumor sites were the pancreas (n=25, 35%), stomach (n=8, 11%), gall bladder (n=4, 6%) and rectum (n=3, 4%). Twenty-five patients (35%) had occult primary tumor. Twelve patients (17%) had histological grade G1 tumors, 30 patients (42%) had G2 tumors, and 30 patients (42%) had G3 tumors. The mean follow-up period after histological confirmation of hepatic metastases was 11.30±2.44 months for G3 tumors, 19.67±4.09 months for G2 tumors, and 30.67±6.51 months for G1 tumors. Multivariate analyses revealed that an unknown primary tumor site (p=0.001) and higher histological grade (p < 0.001) were independent prognostic indicators for shorter overall survival (OS). Most long-term survivors (OS > 24 months) had received antitumor treatment. Conclusion The primary tumor site most frequently associated with GEP NETLM was the pancreas. Unknown primary tumor and higher histological grade were independent prognostic indicators for shorter OS. Patients identified as being at a risk of shorter OS should be followed up closely.

Citations

Citations to this article as recorded by  
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    Huiyu Yang, Lin Zhao, Xiang Jing, Yanmin Kan
    Journal of Clinical Ultrasound.2025;[Epub]     CrossRef
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    Abuduhaibaier Sadula, Gang Li, Dianrong Xiu, Chen Ye, Siqian Ren, Xin Guo, Chunhui Yuan, Min Tang
    Computational and Mathematical Methods in Medicine.2022; 2022: 1.     CrossRef
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    Xiaoxiao Jiao, Wenqing Luan, Xiaoqian Peng, Lu Liu, Lianfeng Zhang, Lin Zhou
    Medicine.2020; 99(51): e23655.     CrossRef
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    Xiao-Ning Kang, Xiao-Yu Zhang, Jie Bai, Zun-Yi Wang, Wen-Jie Yin, Li Li
    World Journal of Gastrointestinal Oncology.2019; 11(5): 436.     CrossRef
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    Lingaku Lee, Tetsuhide Ito, Robert T Jensen
    Expert Review of Anticancer Therapy.2019; 19(12): 1029.     CrossRef
  • A Case Report: Gastric Mixed Neuroendocrine-Nonneuroendocrine Neoplasm with Aggressive Neuroendocrine Component
    Quang Duy Pham, Ichiro Mori, Robert Y. Osamura
    Case Reports in Pathology.2017; 2017: 1.     CrossRef
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    Mitsuru Sugimoto, Tadayuki Takagi, Rei Suzuki, Naoki Konno, Hiroyuki Asama, Ko Watanabe, Jun Nakamura, Hitomi Kikuchi, Yuichi Waragai, Mika Takasumi, Satoshi Kawana, Yuko Hashimoto, Takuto Hikichi, Hiromasa Ohira
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    Yong Gyun Won, Kyung-Jin Seo, Jiyeon Hyeon, Ok Ran Shin, Eundeok Chang, Der Sheng Sun, Hae Sung Won, Yoon Ho Ko, Sae Jung Na, Su Lim Lee, Young Mi Ku, Dong Soo Lee
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    Liangtao Ye, Huilin Ye, Quanbo Zhou, Zhihua Li, Qing Lin, Langping Tan, Wenchao Gao, Zhiqiang Fu, Shangyou Zheng, Rufu Chen
    International Journal of Surgery.2016; 29: 108.     CrossRef
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    Bita Geramizadeh, Ali Kashkooe, Seyed Ali Malekhosseini
    Hepatitis Monthly.2016;[Epub]     CrossRef
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    Deepak Kalyansingh Burad, Thomas Alex Kodiatte, Sayd Mohamed Rajeeb, Ashish Goel, Chundamannil Eapen Eapen, Banumathi Ramakrishna
    World Journal of Gastroenterology.2016; 22(40): 8956.     CrossRef
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    Kazuhiro Kishi, Akihiko Fujisawa, Minoru Horikita, Yoshihiro Nakai, Kazushi Ooshimo, Fumiko Kishi, Masako Kimura, Chun-che Lin, Tetsuji Takayama
    The Journal of Medical Investigation.2015; 62(3.4): 251.     CrossRef
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Current Trends of the Incidence and Pathological Diagnosis of Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs) in Korea 2000-2009: Multicenter Study
Mee-Yon Cho, Joon Mee Kim, Jin Hee Sohn, Mi-Jung Kim, Kyoung-Mee Kim, Woo Ho Kim, Hyunki Kim, Myeong-Cherl Kook, Do Youn Park, Jae Hyuk Lee, HeeKyung Chang, Eun Sun Jung, Hee Kyung Kim, So-Young Jin, Joon Hyuk Choi, Mi Jin Gu, Sujin Kim, Mi Seon Kang, Chang Ho Cho, Moon-Il Park, Yun Kyung Kang, Youn Wha Kim, Sun Och Yoon, Han Ik Bae, Mee Joo, Woo Sung Moon, Dae Young Kang, Sei Jin Chang
Cancer Res Treat. 2012;44(3):157-165.   Published online September 30, 2012
DOI: https://doi.org/10.4143/crt.2012.44.3.157
AbstractAbstract PDFPubReaderePub
PURPOSE
As a result of various independently proposed nomenclatures and classifications, there is confusion in the diagnosis and prediction of biological behavior of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). A comprehensive nationwide study is needed in order to understand the biological characteristics of GEP-NETs in Korea.
MATERIALS AND METHODS
We collected 4,951 pathology reports from 29 hospitals in Korea between 2000 and 2009. Kaplan-Meier survival analysis was used to determine the prognostic significance of clinicopathological parameters.
RESULTS
Although the GEP-NET is a relatively rare tumor in Korea, its incidence has increased during the last decade, with the most significant increase found in the rectum. The 10-year survival rate for well-differentiated endocrine tumor was 92.89%, in contrast to 85.74% in well differentiated neuroendocrine carcinoma and 34.59% in poorly differentiated neuroendocrine carcinoma. Disease related death was most common in the biliary tract (62.2%) and very rare in the rectum (5.2%). In Kaplan-Meier survival analysis, tumor location, histological classification, extent, size, mitosis, Ki-67 labeling index, synaptophysin expression, lymphovascular invasion, perineural invasion, and lymph node metastasis showed prognostic significance (p<0.05), however, chromogranin expression did not (p=0.148). The 2000 and 2010 World Health Organization (WHO) classification proposals were useful for prediction of the prognosis of GEP-NET.
CONCLUSION
The incidence of GEP-NET in Korea has shown a remarkable increase during the last decade, however, the distribution of tumors in the digestive system differs from that of western reports. Assessment of pathological parameters, including immunostaining, is crucial in understanding biological behavior of the tumor as well as predicting prognosis of patients with GEP-NET.

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The Relation between Histopathologic Findings on Surgical Specimen and Outcomes in Patients with N2 Positive Stage IIIA Non-Small Cell Lung Cancer Receiving Preoperative Concurrent Radiochemotherapy and Surgery
Bo Kyong Kim, Kyoung Ju Kim, Yong Chan Ahn, Do Hoon Lim, Won Park, Joungho Han, Keunchil Park, Kwan Min Kim, Jhingook Kim, Young Mog Shim
Cancer Res Treat. 2003;35(6):497-501.   Published online December 31, 2003
DOI: https://doi.org/10.4143/crt.2003.35.6.497
AbstractAbstract PDF
PURPOSE
To evaluate the prognostic implication of histopathologic findings on the surgical specimens of N2 positive stage IIIA non-small cell lung cancer (NSCLC) patients who were treated with preoperative concurrent radiochemotherapy (CRCT) and surgery. MATERIALS AND METHODS: From May 1997 to April 2000, 48 patients with N2 positive stage IIIA NSCLC were treated with preoperative CRCT and surgery. Retrospective analyses were performed on 33 patients who underwent surgical resection. The thoracic radiation therapy (TRT) dose was 45 Gy over 5 weeks with a 1.8 Gy daily fraction using 10 MV X-rays. Chemotherapy consisted of two cycles of intravenous cisplatin (100 mg/m2, on days 1 and 29) and oral etoposide (50 mg/m2/day, on days 1~14 and 29~42), concurrently delivered with TRT. Surgery was performed around 4 weeks of the completion of CRCT. The median follow up was 18 months. The histopathologic findings, including the proportions of viable tumor cells, fibrosis, and necrosis, as well as the tumor and nodal statuses on the surgical specimens following the preoperative CRCT, were analyzed. RESULTS: The 3-year overall survival, disease-free survival, and local control rates were 46.1%, 49.5%, and 85.5%, respectively. Post-surgical stages decreased in 18 patients (54.5%), including 3 pathologic complete responses, were unchanged in 13 (39.4%), and increased in two (6.1%). On univariate analyses, the low proportion of the viable tumor cells was the only factor favorably affecting the overall survival rate (p=0.0386), and the histologic type of squamous cell carcinoma was a favorable factor affecting disease free survival rate (p=0.0452). On multivariate analyses, however, no factor affected the overall survival, disease free survival, or local control rates. CONCLUSION: The histopathologic findings of the proportion of viable tumor cells, fibrosis, and necrosis on the surgical specimens following preoperative CRCT had few prognostic implications on uni-and multi-variate analyses. Furthermore, the primary tumor and nodal responses to preoperative CRCT did not influence the outcomes. Longer-term follow-up with a larger number of patients, however, is awaited.
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Correlation of Ultrasonographic Findings and Pathologic Prognostic Predictions in Breast Cancer
Hyung Il Seo, Hi Sook Kwak, Hong Jae Jo, Tae Yong Jeon, Young Tae Bae, Mun Sup Sim
Cancer Res Treat. 2001;33(4):296-301.   Published online August 31, 2001
DOI: https://doi.org/10.4143/crt.2001.33.4.296
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PURPOSE
Increased technologic capabilities have allowed for the expanded use of ultrasound beyond simple differentiation of a lesion as solid versus cystic nature, allowing us to classify lesions into various categories based on a number of descriptive features. The purpose of this study was to investigate whether to predict the preoperative prognosis of breast cancer through the correlation between ultrasonographic images and the grade of malignancy.
MATERIALS AND METHODS
The patient population for this study consisted of 107 patients with infiltrative ductal carcinoma who were evaluated using ultrasound technology. Ultrasonographic findings were divided as follows: Type I, round or oval shape and regular border; Type II, partially round or oval shape and partially irregular border; and Type III, irregular shape and irregular border.
RESULTS
1. The frequency of grade 1 (G1) was significantly higher in the Type I group than the othergroups. 2. In the 2.0 cm sized mass, the lymph node metastasis rate was significantly lower in the Type I group than the other groups. 3. In all the groups, Estrogen receptor (ER) positivity was insignificant regardless of tumor size and type. 4. In the 2.0 cm sized mass, c-erbB-2 positivity was significantly lower in the Type I than the other groups. There was no clear difference among the three groups in tumors greater than 2.0 cm in size.
CONCLUSION
These results show that our classification of ultrasonographic images reflect the grade of malignancy in terms of clinicopathological features in breast cancers less than 2.0 cm in size. Therefore, ultrasonographic findings may help predict the preoperative prognosis in T1 size breast cancer, although further study is required.
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Clinicopathologic Characteristics and p53, c-erbB2, nm23 Protein Expression in Gastric Remnant Cancer
Joo Ho Lee, Yoe Kyu Youn, Woo Ho Kim, Hang Jong Yu, Byoung Jo Suh, Han Kwang Yang, Kuk Jin Choe, Jin Pok Kim
J Korean Cancer Assoc. 2000;32(1):26-37.
AbstractAbstract PDF
PURPOSE
The goal of this study was to evaluate the clinicopathologic characteristics and to investigate the expression of p53, c-erbB2, and nm23 protein in gastric remnant cancer.
MATERIALS AND METHODS
We evaluated the clinicopathologic characteristics and expression of p53, c-erbB2, and nm23 protein in 37 cases gastric remnant cancer (GRC) that detected at least 5 years after initial surgery, and compare them with adenocarcinoma from intact stomach. Twenty-seven patients among the 37 patients of GRC and 271 patients of primary gastric cancer (PGC) were chosen for immunohistochemical staining against p53, c-erbB2, and nm23.
RESULTS
The median age was 59 years, male was predominant and median time interval between operations were 15 years. GRC initially operated for benign disease were detected later after initial gastrectomy and had a tendency toward lymph node metastasis than those initially operated for malignant disease. Resection was performed in 31 patients (81.0%) in whom 28 patient (71.0%) with curative intent. The overall 5-year survival rate was 44.8%. Multivariate analysis had revealed that depth of invasion was the most significant prognostic factor. p53, c-erbB2, and nm23 protein expression rates of GRC were 44.4%, 14.8%, and 66.7%, respectively and those of PGC were 45.4%, 16.2%, and 85.1%, respectively. p53 protein was more frequently expressed in well differentiated, Laurens intestinal carcinoma in both GRC and PGC. p53 protein expression and depth of invasion had an inverse relationship only in GRC. c-erbB2 protein was more frequently expressed in well differentiated, Laurens intestinal carcinoma in PGC. nm23 protein expression was more frequently expressed in the group of positive lymph node metastasis in GRC.
CONCLUSION
Early detection by periodic endoscopic follow-up and radical resection is a reasonable treatment policy for GRC. The results of p53, c-erbB2, and nm23 expression suggest that they might have somewhat different roles in the pathogenesis and progression in GRC and PGC, so further study may be of benefit hereafter.
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Cancer Res Treat : Cancer Research and Treatment
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