Cancer Research and Treatment

Original Articles

Effectiveness and Safety of Regorafenib and TAS-102 in Patients with Metastatic Colorectal Cancer: A Nationwide Population-Based Study in Taiwan: Ya-Wen Chang, Chun-Nan Kuo, Chia-Lun Chang, Jason C. Hsu, Yu Ko; Received April 16, 2024 Accepted November 16, 2024 Published online November 18, 2024; DOI: https://doi.org/10.4143/crt.2024.376 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Purpose
This study aimed to examine the real-world effectiveness and safety of regorafenib and trifluridine/tipiracil (TAS-102) in metastatic colorectal cancer (mCRC) patients in Taiwan.
Materials and Methods
Data were extracted from Taiwan’s National Health Insurance Research Database to evaluate the clinical outcomes of mCRC patients treated with either regorafenib or TAS-102 between 2016 and 2019. Overall survival (OS) was compared using Kaplan-Meier curves and Cox’s proportional hazard models, adjusting for age, sex, Quan-CCI score, liver metastases, number of metastatic sites, and the use of anti–epidermal growth factor receptor medications. Additionally, OS was compared between regorafenib monotherapy and TAS-102 monotherapy, excluding patients who had received both regorafenib and TAS-102.
Results
A total of 2,608 patients in the regorafenib group and 521 patients in the TAS-102 group were identified. The median OS was 6.5 months for regorafenib and 7.5 months for TAS-102, with a significant difference observed (p=0.001). The mean duration of treatment was similar for regorafenib and TAS-102 (108 days vs. 101 days) with no significant difference. The safety profiles of the two drugs were distinct; a higher proportion of patients in the regorafenib group had hypertension and hand-foot skin reaction while nausea and vomiting were more common in the TAS-102 group. In the subgroup analysis, patients receiving TAS-102 monotherapy showed significantly longer OS than those receiving regorafenib monotherapy.
Conclusion
The findings of this study indicated that TAS-102 had superior survival outcomes compared to regorafenib in mCRC patients. This study provides insights into the effectiveness and safety profiles of regorafenib and TAS-102 in Taiwan.

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Breast cancer

Temporal Trend in Uptake of the National General Health Checkups and Cancer Screening Program among Korean Women with Breast Cancer: Thi Xuan Mai Tran, Soyeoun Kim, Chihwan Cha, Boyoung Park; Cancer Res Treat. 2024;56(2):522-530. Published online October 30, 2023; DOI: https://doi.org/10.4143/crt.2023.729

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study assessed the temporal trends of uptake of national general health and cancer screening among women with breast cancer in Korea between 2009 and 2016.
Materials and Methods
We retrospectively analyzed the claims data from the Korean National Health Insurance Service database. Participants included 101,403 breast cancer patients diagnosed between 2009 and 2016. Information on participation in national screening programs, including breast cancer screening, general health, and gastric, colorectal, and cervical cancers, up to 2020 was collected. Screening participation rates within the first 2 and 5 years postdiagnosis were calculated by diagnosis year and fitted with joinpoint regression models to assess temporal trends.
Results
Overall, the participation rate in breast cancer screening within 2 years postdiagnosis increased from 10.9% to 14.0% from 2009-2016, with an annual percentage change (APC) of 3.7% (p < 0.05). The participation rate in breast cancer screening was lower than that in general health checkup and screening for other cancers within 2 and 5 years postdiagnosis. A steady increase in screening trends was also observed for general health, gastric, colorectal, and cervical cancers, with APC of 5.3%, 5.7%, 6.9%, and 7.6% in the 2-year postdiagnosis rate, and APC of 3.6%, 3.7%, 3.7%, and 4.4% in 5-year postdiagnosis rate, respectively. The screening rate was highest among age groups 50-59 and 60-69 in 2009 and significant upward trends were observed in all age groups for general health checkup and gastric, colorectal, and cervical cancer screening.
Conclusion
Among female breast cancer survivors in Korea, the uptake rate of screenings for general health and various cancers, including breast, gastric, colorectal, and cervical cancers, has shown a gradual increase in recent years.

Citations

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Identifying potential medical aid beneficiaries using machine learning: A Korean Nationwide cohort study
Junmo Kim, Su Hyun Park, Hyesu Lee, Su Kyoung Lee, Jihye Kim, Suhyun Kim, Yong Jin Kwon, Kwangsoo Kim
International Journal of Medical Informatics.2025; 195: 105775. CrossRef
Screening Adherence for Second Primary Malignancies in Breast Cancer Survivors: Behaviors, Facilitators, and Barriers to Enhance Quality Care
Fernanda Mesa-Chavez, Misael Salazar-Alejo, Cynthia Villarreal-Garza
Seminars in Oncology.2024; 51(5-6): 156. CrossRef

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Gastrointestinal cancer

Specific Mutations in APC, with Prognostic Implications in Metastatic Colorectal Cancer: Huan Peng, Jun Ying, Jia Zang, Hao Lu, Xiaokai Zhao, Pengmin Yang, Xintao Wang, Jieyi Li, Ziying Gong, Daoyun Zhang, Zhiguo Wang; Cancer Res Treat. 2023;55(4):1270-1280. Published online April 24, 2023; DOI: https://doi.org/10.4143/crt.2023.415

Abstract PDF Supplementary Material PubReader ePub

Purpose
Loss-of-function mutations in the adenomatous polyposis coli (APC) gene are common in metastatic colorectal cancer (mCRC). However, the characteristic of APC specific mutations in mCRC is poorly understood. Here, we explored the clinical and molecular characteristics of N-terminal and C-terminal side APC mutations in Chinese patients with mCRC.
Materials and Methods
Hybrid capture-based next-generation sequencing was performed on tumor tissues from 275 mCRC pati-ents to detect mutations in 639 tumor-associated genes. The prognostic value and gene-pathway difference between APC specific mutations in mCRC patients were analyzed.
Results
APC mutations were highly clustered, accounting for 73% of all mCRC patients, and most of them were truncating mutations. The tumor mutation burden of the N-terminal side APC mutations group (n=76) was significantly lower than that of the C-terminal side group (n=123) (p < 0.001), further confirmed by the public database. Survival analysis showed that mCRC patients with N-terminus side APC mutations had longer overall survival than C-terminus side. Tumor gene pathway analysis showed that gene mutations in the RTK/RAS, Wnt and transforming growth factor β signaling pathways of the C-terminal group were significantly higher than those of the N-terminal group (p < 0.05). Additionally, KRAS, AMER1, TGFBR2, and ARID1A driver mutations were more common in patients with C-terminal side APC mutations.
Conclusion
APC specific mutations have potential function as mCRC prognostic biomarkers. There are obvious differences in the gene mutation patterns between the C-terminus and N-terminus APC mutations group, which may have certain guiding significance for the subsequent precise treatment of mCRC.

Citations

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In Silico Validation of OncoOrigin: An Integrative AI Tool for Primary Cancer Site Prediction with Graphical User Interface to Facilitate Clinical Application
Petar Brlek, Luka Bulić, Nidhi Shah, Parth Shah, Dragan Primorac
International Journal of Molecular Sciences.2025; 26(6): 2568. CrossRef
Wnt signaling in cancer: from biomarkers to targeted therapies and clinical translation
Muhammad Tufail, Can-Hua Jiang, Ning Li
Molecular Cancer.2025;[Epub] CrossRef
Advances in Precision Medicine Approaches for Colorectal Cancer: From Molecular Profiling to Targeted Therapies
Neelakanta Sarvashiva Kiran, Chandrashekar Yashaswini, Rahul Maheshwari, Sankha Bhattacharya, Bhupendra G. Prajapati
ACS Pharmacology & Translational Science.2024; 7(4): 967. CrossRef
Clinical implications of PD-L1 expression and pathway-related molecular subtypes in advanced Asian colorectal cancer patients
Qingqing Qiu
American Journal of Cancer Research.2024; 14(2): 796. CrossRef
Mechanism of APC truncation involved in colorectal cancer tumorigenesis (Review)
Tuya Wang, Jing Fu, Ye Huang, Chun Fu
Oncology Letters.2024;[Epub] CrossRef

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Trastuzumab Combined with Irinotecan in Patients with HER2-Positive Metastatic Colorectal Cancer: A Phase II Single-Arm Study and Exploratory Biomarker Analysis: Ting Xu, Xicheng Wang, Ying Xin, Zhenghang Wang, Jifang Gong, Xiaotian Zhang, Yanyan Li, Congcong Ji, Yu Sun, Feilong Zhao, Depei Huang, Yuezong Bai, Jian Li, Lin Shen; Cancer Res Treat. 2023;55(2):626-635. Published online December 23, 2022; DOI: https://doi.org/10.4143/crt.2022.1058

Abstract PDF Supplementary Material PubReader ePub

Purpose
The human epidermal growth factor receptor 2 (HER2) is an established therapeutic target for various kinds of solid tumors. HER2 amplification occurs in approximately 1% to 6% of colorectal cancer. In this study, we aimed to assess the efficacy and safety of trastuzumab in combination with chemotherapy in HER2-positive metastatic colorectal cancer (mCRC).
Materials and Methods
An open-label, phase II trial (Clinicaltrials.gov: NCT03185988) was designed to evaluate the antitumor activity of trastuzumab and chemotherapy in HER2-positive digestive cancers excluding gastric cancer in 2017. Patients from this trial with HER2-positive, KRAS/BRAF wild-type, unresectable mCRC were analyzed in this manuscript. Eligible patients were treated with trastuzumab (8 mg/kg loading dose and then 6 mg/kg every 3 weeks) and irinotecan (120 mg/m² days 1 and 8 every 3 weeks). The primary endpoint was the objective response rate.
Results
Twenty-one HER2-positive mCRC patients were enrolled in this study. Seven patients (33.3%) achieved an objective res-ponse, and 11 patients (52.4%) had stable disease as their best response. The median progression-free survival (PFS) was 4.3 months (95% confidence interval, 2.7 to 5.9). Four of the 21 patients (19.0%) had grade 3 adverse events, including leukopenia, neutropenia, urinary tract infection, and diarrhea. No treatment-related death was reported. Exploratory analyses revealed that high tumor tissue HER2 copy number was associated with better therapeutic response and PFS. Alterations in the mitogen-activated protein kinase pathway, HER2 gene, phosphoinositide 3-kinase/AKT pathway, and cell cycle control genes were potential drivers of trastuzumab resistance in mCRC.
Conclusion
Trastuzumab combined with chemotherapy is a potentially effective and well-tolerated therapeutic regimen in mCRC with a high HER2 copy number.

Citations

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HER2-targeted therapy in colorectal cancer: a comprehensive review
Yeliz Benli, Helin Arıkan, Özge Akbulut-Çalışkan
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Mehrshad Ebrahimpour, Hamidreza Hosseinzadeh, Farshad Abedi, Mohammad Moeini Nodeh, Abolghasem Allahyari, Amirhossein Sahebkar, Omid Arasteh
Naunyn-Schmiedeberg's Archives of Pharmacology.2024; 397(7): 4601. CrossRef
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Zhen Liu, Yajie Yuan, Ning Wang, Peng Yu, Yuou Teng
European Journal of Medicinal Chemistry.2024; 279: 116872. CrossRef
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Amol A. Dixit, Deepa S. Mandlik, Satish K. Mandlik
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Nimotuzumab and irinotecan synergistically induce ROS‐mediated apoptosis by endoplasmic reticulum stress and mitochondrial‐mediated pathway in cervical cancer
Fei Teng, Lujun Zhao
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Current Targeted Therapy for Metastatic Colorectal Cancer
Tomokazu Ohishi, Mika K. Kaneko, Yukihiro Yoshida, Atsuo Takashima, Yukinari Kato, Manabu Kawada
International Journal of Molecular Sciences.2023; 24(2): 1702. CrossRef
Immune Checkpoint Inhibitor-Based Combination Therapy for Colorectal Cancer: An Overview
Jingjing Li, Xuanfu Xu
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Mechanism of multidrug resistance to chemotherapy mediated by P‑glycoprotein (Review)
Yichen Tian, Yongrong Lei, Yani Wang, Jiejuan Lai, Jianhua Wang, Feng Xia
International Journal of Oncology.2023;[Epub] CrossRef
Successful treatment with trastuzumab plus chemotherapy as the first‑line regimen in advanced small bowel adenocarcinoma harboring HER2 amplification: A report of two cases
Jingwen Wang, Xia Zhu, Jiayan Chen, Fei Liu, Xi Tang
Oncology Letters.2023;[Epub] CrossRef

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Universal Screening for Lynch Syndrome Compared with Pedigree-Based Screening: 10-Year Experience in a Tertiary Hospital: Min Hyun Kim, Duck-Woo Kim, Hye Seung Lee, Su Kyung Bang, Soo Hyun Seo, Kyung Un Park, Heung-Kwon Oh, Sung-Bum Kang; Cancer Res Treat. 2023;55(1):179-188. Published online March 21, 2022; DOI: https://doi.org/10.4143/crt.2021.1512

Abstract PDF PubReader ePub

Purpose
Universal screening for Lynch syndrome (LS) refers to routine tumor testing for microsatellite instability (MSI) among all patients with colorectal cancer (CRC). Despite its widespread adoption, real-world data on the yield is lacking in Korean population. We studied the yield of adopting universal screening for LS in comparison with pedigree-based screening in a tertiary center.
Materials and Methods
CRC patients from 2007-2018 were reviewed. Family histories were obtained and were evaluated for hereditary nonpolyposis colorectal cancer (HNPCC) using Amsterdam II criteria. Tumor testing for MSI began in 2007 and genetic testing was offered using all available clinicopathologic data. Yield of genetic testing for LS was compared for each approach and step.
Results
Of the 5,520 patients, tumor testing was performed in 4,701 patients (85.2%) and family histories were obtained from 4,241 patients (76.8%). Hereditary CRC (LS or HNPCC) was present in 69 patients (1.3%). MSI-high was present in 6.9%, and 25 patients had confirmed LS. Genetic testing was performed in 41.2% (47/114) of MSI-high patients, out of which 40.4% (19/47) were diagnosed with LS. There were six additional LS patients found outside of tumor testing. For pedigree-based screening, Amsterdam II criteria diagnosed 55 patients with HNPCC. Fifteen of these patients underwent genetic testing, and 11 (73.3%) were diagnosed with LS. Two patients without prior family history were diagnosed with LS and relied solely on tumor testing results.
Conclusion
Despite widespread adoption of routine tumor testing for MSI, this is not a fail-safe approach to screen all LS patients. Obtaining a thorough family history in combination with universal screening provides a more comprehensive ‘universal’ screening method for LS.

Citations

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Hereditary Colorectal Cancer: From Diagnosis to Surgical Options
Rami James N. Aoun, Matthew F. Kalady
Clinics in Colon and Rectal Surgery.2025; 38(03): 179. CrossRef
Colon cancer: the 2023 Korean clinical practice guidelines for diagnosis and treatment
Hyo Seon Ryu, Hyun Jung Kim, Woong Bae Ji, Byung Chang Kim, Ji Hun Kim, Sung Kyung Moon, Sung Il Kang, Han Deok Kwak, Eun Sun Kim, Chang Hyun Kim, Tae Hyung Kim, Gyoung Tae Noh, Byung-Soo Park, Hyeung-Min Park, Jeong Mo Bae, Jung Hoon Bae, Ni Eun Seo, Cha
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Universal screening of colorectal tumors for lynch syndrome: a survey of patient experiences and opinions
Alexander T. Petterson, Jennifer Garbarini, Maria J. Baker
Hereditary Cancer in Clinical Practice.2024;[Epub] CrossRef
Genetic Testing for Prostate Cancer, Urothelial Cancer, and Kidney Cancer
Hyunho Han, Minyong Kang, Seok-Soo Byun, Seok Joong Yun
Journal of Urologic Oncology.2023; 21(2): 128. CrossRef
Diagnosis of patients with Lynch syndrome lacking the Amsterdam II or Bethesda criteria
Miguel Angel Trujillo-Rojas, María de la Luz Ayala-Madrigal, Melva Gutiérrez-Angulo, Anahí González-Mercado, José Miguel Moreno-Ortiz
Hereditary Cancer in Clinical Practice.2023;[Epub] CrossRef
Hereditary Colorectal Cancer: State of the Art in Lynch Syndrome
Antonio Nolano, Alessia Medugno, Silvia Trombetti, Raffaella Liccardo, Marina De Rosa, Paola Izzo, Francesca Duraturo
Cancers.2022; 15(1): 75. CrossRef

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Radiofrequency Ablation versus Stereotactic Body Radiation Therapy in the Treatment of Colorectal Cancer Liver Metastases: Jesang Yu, Dong Hwan Kim, Jungbok Lee, Yong Moon Shin, Jong Hoon Kim, Sang Min Yoon, Jinhong Jung, Jin Cheon Kim, Chang Sik Yu, Seok-Byung Lim, In Ja Park, Tae Won Kim, Yong Sang Hong, Sun Young Kim, Jeong Eun Kim, Jin-hong Park, So Yeon Kim; Cancer Res Treat. 2022;54(3):850-859. Published online October 13, 2021; DOI: https://doi.org/10.4143/crt.2021.674

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to compare the treatment outcomes of radiofrequency ablation (RFA) and stereotactic body radiation therapy (SBRT) for colorectal cancer liver metastases (CRLM) and to determine the favorable treatment modality according to tumor characteristics.
Materials and Methods
We retrospectively analyzed the records of 222 colorectal cancer patients with 330 CRLM who underwent RFA (268 tumors in 178 patients) or SBRT (62 tumors in 44 patients) between 2007 and 2014. Kaplan–Meier method and Cox models were used by adjusting with inverse probability of treatment weighting (IPTW).
Results
The median follow-up duration was 30.5 months. The median tumor size was significantly smaller in the RFA group than in the SBRT group (1.5 cm vs 2.3 cm, p<0.001). In IPTW-adjusted analysis, difference in treatment modality was not associated with significant differences in 1-year and 3-year recurrence-free survival (35% vs 43%, 22% vs 23%; p=0.198), overall survival (96% vs 91%, 58% vs 56%; p=0.508), and freedom from local progression (FFLP; 90% vs 72%, 78% vs 60%; p=0.106). Significant interaction effect between the treatment modality and tumor size was observed for FFLP (p=0.001). In IPTW-adjusted subgroup analysis of patients with tumor size >2 cm, the SBRT group had a higher FFLP compared with the RFA group (HR, 0.153; p<0.001).
Conclusion
SBRT and RFA showed similar local control in the treatment of patients with CRLM. Tumor size was an independent prognostic factor for local control and SBRT may be preferred for larger tumors.

Citations

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Ablative techniques in colorectal liver metastases: A systematic review, descriptive summary of practice, and recommendations for optimal data reporting
Wee Han Ng, Catarina Machado, Alice Rooney, Robert Jones, Jonathan Rees, Samir Pathak
European Journal of Surgical Oncology.2025; 51(2): 109487. CrossRef
Effects of maximum dose on local control after stereotactic body radiotherapy for oligometastatic tumors of colorectal cancer
Su Jin Kang, Jongmoo Park, Gyu-Seog Choi, Jong Gwang Kim, Jun Seok Park, Hye Jin Kim, Jin Ho Baek, Byung Woog Kang, An Na Seo, Shin-Hyung Park, Bong Kyung Bae, Min Kyu Kang, Soo Yeun Park, Devarati Mitra
PLOS ONE.2025; 20(1): e0313438. CrossRef
Treatment of Oligometastatic GI Cancers
Clayton T. Marcinak, Patrick B. Schwartz, Mustafa M. Basree, Newton Hurst, Michael Bassetti, Jeremy D. Kratz, Nataliya V. Uboha
American Society of Clinical Oncology Educational Book.2024;[Epub] CrossRef
Stereotactic radiotherapy for liver oligometastases: a pooled analysis following the estro/eortc consensus recommendations
D. Pezzulla, G. Chiloiro, E. M. Lima, G. Macchia, C. Romano, S. Reina, G. Panza, S. Cilla, A. G. Morganti, F. Cellini, M. A. Gambacorta, F. Deodato
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Interventionelle Therapieoptionen bei oligometastasierten Tumoren
Max Seidensticker
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Efficacy and safety of B-ultrasound-guided radiofrequency ablation in the treatment of primary liver cancer: Systematic review and meta-analysis
Xiong Zhang, Hong-Yi Zhu, Ming Yuan
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Wen-Yu Huang, Sheng Zheng, Dan Zhu, Ying-Lang Zeng, Juan Yang, Xue-Li Zeng, Pei Liu, Shun-Ling Zhang, Ming Yuan, Zhi-Xia Wang
World Journal of Gastrointestinal Surgery.2024; 16(9): 2860. CrossRef
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Hwa Kyung Byun, Gyu Sang Yoo, Soo-Yoon Sung, Jin-Ho Song, Byoung Hyuck Kim, Yoo-Kang Kwak, Yeon Joo Kim, Yeon-Sil Kim, Kyung Su Kim
Radiation Oncology Journal.2024; 42(4): 247. CrossRef
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Kyungmi Yang, Jeong Eun Lee, Won Park, Yong Chan Ahn, Seung Jae Huh
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Federica Borrelli de Andreis, Maria Alessandra Calegari, Angela Romano, Maria Gabriella Brizi, Luigi Sofo, Ivo Boskoski, Guido Costamagna, Fabia Attili
Current Problems in Cancer: Case Reports.2023; 9: 100216. CrossRef
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Chai Hong Rim, Jung Sue Lee, Soo Yeon Kim, Jinsil Seong
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Gyu Sang Yoo, Chai Hong Rim, Won Kyung Cho, Jae-Uk Jeong, Eui Kyu Chie, Hyeon-Min Cho, Jun Won Um, Yong Chan Ahn, Jong Hoon Lee
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Sara Mheid, Stefan Allen, Sylvia S. W. Ng, William A. Hall, Nina N. Sanford, Todd A. Aguilera, Ahmed M. Elamir, Rana Bahij, Martijn P. W. Intven, Ganesh Radhakrishna, Issa Mohamad, Jeremy De Leon, Hendrick Tan, Shirley Lewis, Cihan Gani, Teo Stanecu, Vero
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Evidence on percutaneous radiofrequency and microwave ablation for liver metastases over the last decade
Koji Tomita, Yusuke Matsui, Mayu Uka, Noriyuki Umakoshi, Takahiro Kawabata, Kazuaki Munetomo, Shoma Nagata, Toshihiro Iguchi, Takao Hiraki
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Gastrointestinal Cancer

LASSO-Based Machine Learning Algorithm for Prediction of Lymph Node Metastasis in T1 Colorectal Cancer: Jeonghyun Kang, Yoon Jung Choi, Im-kyung Kim, Hye Sun Lee, Hogeun Kim, Seung Hyuk Baik, Nam Kyu Kim, Kang Young Lee; Cancer Res Treat. 2021;53(3):773-783. Published online December 29, 2020; DOI: https://doi.org/10.4143/crt.2020.974

Abstract PDF Supplementary Material PubReader ePub

Purpose
The role of tumor-infiltrating lymphocytes (TILs) in predicting lymph node metastasis (LNM) in patients with T1 colorectal cancer (CRC) remains unclear. Furthermore, clinical utility of a machine learning–based approach has not been widely studied.
Materials and Methods
Immunohistochemistry for TILs against CD3, CD8, and forkhead box P3 in both center and invasive margin of the tumor were performed using surgically resected T1 CRC slides. Three hundred and sixteen patients were enrolled and categorized into training (n=221) and validation (n=95) sets via random sampling. Using clinicopathologic variables including TILs, the least absolute shrinkage and selection operator (LASSO) regression model was applied for variable selection and predictive signature building in the training set. The predictive accuracy of our model and the Japanese criteria were compared using area under the receiver operating characteristic (AUROC), net reclassification improvement (NRI)/integrated discrimination improvement (IDI), and decision curve analysis (DCA) in the validation set.
Results
LNM was detected in 29 (13.1%) and 12 (12.6%) patients in training and validation sets, respectively. Nine variables were selected and used to generate the LASSO model. Its performance was similar in training and validation sets (AUROC, 0.795 vs. 0.765; p=0.747). In the validation set, the LASSO model showed better outcomes in predicting LNM than Japanese criteria, as measured by AUROC (0.765 vs. 0.518, p=0.003) and NRI (0.447, p=0.039)/IDI (0.121, p=0.034). DCA showed positive net benefits in using our model.
Conclusion
Our LASSO model incorporating histopathologic parameters and TILs showed superior performance compared to conventional Japanese criteria in predicting LNM in patients with T1 CRC.

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Computed Tomography–Determined Sarcopenia Is a Useful Imaging Biomarker for Predicting Postoperative Outcomes in Elderly Colorectal Cancer Patients: Hailun Xie, Yizhen Gong, Jiaan Kuang, Ling Yan, Guotian Ruan, Shuangyi Tang, Feng Gao, Jialiang Gan; Cancer Res Treat. 2020;52(3):957-972. Published online April 17, 2020; DOI: https://doi.org/10.4143/crt.2019.695

Abstract PDF PubReader ePub

Purpose
This study aimed to establish whether computed tomography (CT)–determined sarcopenia is a useful imaging biomarker for postoperative outcome in elderly colorectal cancer (CRC) patients, and construct sarcopenia-based nomograms to predict individual outcomes after surgery.
Materials and Methods
CT imaging data of 298 elderly CRC patients who underwent surgery in 2012-2014 were retrospectively analyzed. Skeletal muscle mass was determined by CT, and sarcopenia was diagnosed based on the optimal cutoff value determined by X-tile program. The correlation between sarcopenia and risk of preoperative nutrition and postoperative complications was evaluated. A Cox proportional hazards model was used to determine survival predictors. Sarcopenia-based nomograms were developed based on multivariate analysis, and calibrated using concordance index and calibration curves.
Results
A total 132 patients (44.3%) had sarcopenia based on the optimum cutoff values (29.9 cm2/m2 for women and 49.5 cm2/m2 for men). Sarcopenia was an independent risk factor for preoperative nutrition (p < 0.001; odds ratio [OR], 3.405; 95% confidence interval [CI], 1.948 to 5.954) and postoperative complications (p=0.008; OR, 2.192; 95% CI, 1.231 to 3.903). Sarcopenia was an independent predictor for poor progression-free survival (p < 0.001; hazard ratio [HR], 2.175; 95% CI, 1.489 to 3.179) and overall survival (p < 0.001; HR, 2.524; 95% CI, 1.721 to 3.703). Based on multivariate analysis, we produced four nomograms that had better predictive performance.
Conclusion
CT-determined sarcopenia is a useful imaging biomarker for predicting preoperative nutritional risk, postoperative complications, and long-term outcomes in elderly CRC patients. The sarcopenia-based nomograms can provide a scientific basis for guiding therapeutic schedule and follow-up strategies.

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Genetic Risk Score, Combined Lifestyle Factors and Risk of Colorectal Cancer: Young Ae Cho, Jeonghee Lee, Jae Hwan Oh, Hee Jin Chang, Dae Kyung Sohn, Aesun Shin, Jeongseon Kim; Cancer Res Treat. 2019;51(3):1033-1040. Published online October 18, 2018; DOI: https://doi.org/10.4143/crt.2018.447

Abstract PDF Supplementary Material PubReader ePub

Purpose
Both genetic and lifestyle factors contribute to the risk of colorectal cancer, but each individual factor has a limited effect. Therefore, we investigated the association between colorectal cancer and the combined effects of genetic factors or/and lifestyle risk factors.
Materials and Methods
In a case-control study of 632 colorectal cancer patients and 1,295 healthy controls, we quantified the genetic risk score for colorectal cancer using 13 polymorphisms. Furthermore, we determined a combined lifestyle risk score including obesity, physical activity, smoking, alcohol consumption, and dietary inflammatory index. The associations between colorectal cancer and risk score using these factors were examined using a logistic regression model.
Results
Higher genetic risk scores were associated with an increased risk of colorectal cancer (odds ratio [OR], 2.57; 95% confidence interval [CI], 1.89 to 3.49 for the highest tertile vs. lowest tertile). Among the modifiable factors, previous body mass index, physical inactivity, heavy alcohol consumption, and a high inflammatory diet were associated with an increased risk of colorectal cancer. A higher lifestyle risk score was associated with an increased risk of colorectal cancer (OR, 5.82; 95% CI, 4.02 to 8.44 for the highest tertile vs. lowest tertile). This association was similar in each genetic risk category.
Conclusion
Adherence to a healthy lifestyle is associated with a substantially reduced risk of colorectal cancer regardless of individuals’ genetic risk.

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Sandra Caramujo-Balseiro, Carlos Faro, Lina Carvalho
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Yanyi Huang, Jinzhong Duanmu, Yushu Liu, Mengyun Yan, Taiyuan Li, Qunguang Jiang
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Individual and Joint Associations of Genetic Risk and Healthy Lifestyle Score with Colorectal Neoplasms Among Participants of Screening Colonoscopy
Vanessa Erben, Prudence R. Carr, Feng Guo, Korbinian Weigl, Michael Hoffmeister, Hermann Brenner
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Marjan Ostovarpour, Mohammad Khalaj-Kondori, Tayyebeh Ghasemi
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Sepideh Kadkhoda, Reza Taslimi, Farshid Noorbakhsh, Farzaneh Darbeheshti, Javad Tavakkoly Bazzaz, Soudeh Ghafouri-Fard, Abbas Shakoori
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Jia Yang, Li Zhao, Nan Zhang, Zhenhua Du, Yanyan Li, Xia Li, Deli Zhao, Jialin Wang
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Justina Ucheojor Onwuka, Dapeng Li, Yupeng Liu, Hao Huang, Jing Xu, Ying Liu, Yuanyuan Zhang, Yashuang Zhao
BMC Cancer.2020;[Epub] CrossRef
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Massimo Rugge
The Lancet Oncology.2020; 21(10): 1258. CrossRef
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Shatha A. Alduraywish, Leen A. Altamimi, Ashwaq A. Almajed, Bushra A. Kokandi, Rawan S. Alqahtani, Shatha G. Alghaihb, Fahad M. Aldakheel
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Protective Effect of Green Tea Consumption on Colorectal Cancer Varies by Lifestyle Factors
Hyejin Kim, Jeonghee Lee, Jae Hwan Oh, Hee Jin Chang, Dae Kyung Sohn, Aesun Shin, Jeongseon Kim
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Jorjani Biomedicine Journal.2019; 7(4): 49. CrossRef

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Thymidylate Synthase, Thymidine Phosphorylase, VEGF and p53 Protein Expression in Primary Colorectal Cancer for Predicting Response to 5-fluorouracil-based Chemotherapy: Myung-Ju Ahn, Jung-Hye Choi, Ho-Suk Oh, Young-Yeul Lee, In-Soon Kim, Il-Young Choi, Kang-Hong Lee, Kang-Won Song, Chan-Kum Park; Cancer Res Treat. 2005;37(4):216-222. Published online August 31, 2005; DOI: https://doi.org/10.4143/crt.2005.37.4.216

Abstract PDF PubReader ePub

Purpose

In the treatment of advanced metastatic colorectal cancer, several new agents, such as irinotecan and oxaliplatin, have been developed, which have improved both disease free and overall survivals. Among these agents, 5-fluorouracil (5-FU) still remains one of the most active agents, and the selection of patients who can benefit from 5-FU-based chemotherapy is still important, as those unlikely to benefit could be spared the harmful side effects. The expression levels of thymidylate synthase (TS), thymidine phosphorylase (TP) and p53 have been known to be associated with the clinical response to 5-FU-based therapy as well as the prognosis, and that of vascular endothelial growth factor (VEGF) is associated with poor survival.

Materials and Methods

The relationship between the expressions of TS, TP, VEGF and p53 in primary tumors, using immunohistochemistry, and the response of 45 metastatic colorectal cancer patients (M:F=25:20, median age 59 yrs) to 5-FU-based chemotherapy were evaluated.

Results

Thirty-seven patients were treated with 5-FU/LV/irinotecan (FOLFIRI) and 8 with 5-FU/LV/oxaplatin (FOLFOX). The overall response rate was 28.9% (13/45). When immunohistochemically analyzed with monoclonal antibodies against TS, TP, VEGF and p53, 55.6% of the patients (25/45) were positive for TS, 48.9% (22/45) for TP, 82.2% (37/45) for VEGF, and 80% (36/45) for p53. There was a significant difference in the intensity of TS expression between the clinical responders and non-responders (p=0.036). In terms of the staining pattern of TS expression, diffuse staining was correlated with a poor response (p=0.012) and poor survival (p=0.045). However, there was no correlation between the expressions of TP, VEGF or P53 and the response to chemotherapy.

Conclusion

These results suggest that the expression of TS in primary colorectal cancer might be an important prognostic factor for chemotherapy response and survival, and might be a useful therapeutic marker for the response of chemotherapy.

Citations

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Epigenetic Approaches to Overcome Fluoropyrimidines Resistance in Solid Tumors
Laura Grumetti, Rita Lombardi, Federica Iannelli, Biagio Pucci, Antonio Avallone, Elena Di Gennaro, Alfredo Budillon
Cancers.2022; 14(3): 695. CrossRef
Immunoexpression of TS, p53, COX2, EGFR, MSH6 and MLH1 biomarkers and its correlation with degree of differentiation, tumor staging and prognostic factors in colorectal adenocarcinoma: a retrospective longitudinal study
Wilson Roberto Batista, Gianni Santos, Flávia Maria Ribeiro Vital, Delcio Matos
Sao Paulo Medical Journal.2019; 137(1): 33. CrossRef
Thymidine phosphorylase expression and prognosis in colorectal cancer treated with 5‑fluorouracil‑based chemotherapy: A meta‑analysis
Jia Che, Lun Pan, Xiangling Yang, Zhiting Liu, Lanlan Huang, Chuangyu Wen, Aihua Lin, Huanliang Liu
Molecular and Clinical Oncology.2017;[Epub] CrossRef
Does anti-p53 antibody status predict for clinical outcomes in metastatic colorectal cancer patients treated with fluoropyrimidine, oxaliplatin, plus bevacizumab as first-line chemotherapy?
Hiroki Osumi, Eiji Shinozaki, Mitsukuni Suenaga, Yosuke Kumekawa, Mariko Ogura, Masato Ozaka, Satoshi Matsusaka, Keisho Chin, Noriko Yamamoto, Nobuyuki Mizunuma
BMC Cancer.2015;[Epub] CrossRef
Comparison of thymidine phosphorylase expression and prognostic factors in gallbladder and bile duct cancer
Hye Sung Won, Myung Ah Lee, Eun-Seon Chung, Dong-Goo Kim, Young Kyoung You, Tae Ho Hong, In-Seok Lee
BMC Cancer.2010;[Epub] CrossRef

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Phase II Study of Irinotecan, 5-Fluorouracil, and Leucovorin in Relapsed or Metastatic Colorectal Cancer as First-line Therapy: Young-Woong Won, Young-Hyo Lim, Ho-Yong Park, Ho-Suk Oh, Jung-Hye Choi, Young-Yeul Lee, In-Soon Kim, Il-Young Choi, Myung-Ju Ahn; Cancer Res Treat. 2004;36(4):235-239. Published online August 31, 2004; DOI: https://doi.org/10.4143/crt.2004.36.4.235

Abstract PDF PubReader ePub

Background

The purpose of this study was to assess the efficacy and toxicity of biweekly irinotecan plus 5-fluorouracil (FU) and leucovorin (LV) in patients with relapsed or metastatic colorectal cancer.

Materials and Methods

Between March 2002 and May 2004, 24 patients with histologically confirmed relapsed or metastatic colorectal cancer were enrolled in this study. One chemotherapy cycle consisted of irinotecan 180 mg/m² on days 1 and 15; 5-FU 400 mg/m² bolus IV with 600 mg/m² by a 22 hour intravenous infusion on days 1, 2, 15 and 16; and leucovorin 20 mg/m² on days 1, 2, 15 and 16, every 4 weeks.

Results

The median age of the 24 was 57.5 years (range, 38~69). Their metastatic sites included: the liver (62.5%), lung (20.8%), peritoneum (16.7%), lymph node (12.5%), ovary (8.3%) and pelvis/vagina (8.3%). Twenty-two patients were evaluable for a response. Six and 7 patients achieved partial responses and stable diseases, respectively. The overall response rate was 27.3% (95% Confidence interval; 10.3~44.5%). The median follow-up duration for surviving patients was 14.7 months (range, 1.7~26.5). Median overall survival (OS) and 1-year OS rates were 19 months and 86.3%, respectively. Median response duration and median progression free survival were 7.47 and 5.57 months, respectively. A total of 83 cycles (median 4 cycles) were administered. The main non-hematologic toxicities were nausea/vomiting (44.5%/18.1%) and diarrhea (8.4%). The most common hematologic toxicity was NCI grade I/II anemia (31.3%) and grade I/II neutropenia was 10.8%. There was no life-threatening toxicity.

Conclusion

The results suggested that irinotecan, 5-FU and leucovorin combination chemotherapy in a biweekly schedule is a practical and tolerable treatment option in patients with advanced colorectal cancer.

Citations

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A Phase I Study of UGT1A1 *28/*6 Genotype-Directed Dosing of Irinotecan (CPT-11) in Korean Patients with Metastatic Colorectal Cancer Receiving FOLFIRI
Kyu-Pyo Kim, Yong Sang Hong, Jae-Lyun Lee, Kyun Seop Bae, Ho-Sook Kim, Jae-Gook Shin, Jung Shin Lee, Tae Won Kim
Oncology.2015; 88(3): 164. CrossRef
Effect of an Irinotencan, 5-Fluorouracil, and Leucovorin Combination Chemotherapy (FOLFIRI) in Metastatic Colorectal Cancer
Seung Hyun Lee, Byung Kwon Ahn, Sung Uhn Baek
Journal of the Korean Society of Coloproctology.2007; 23(5): 333. CrossRef
A Phase II Study of Irinotecan, 5-Fluorouracil and Leucovorin for Treatment in Patients with Previously Untreated Advanced Colorectal Cancer
Sang-Byung Bae, Nam-Su Lee, Han-Jo Kim, Kyoung-Ha Kim, Hyun-Jung Kim, Chan-Kyu Kim, Kyu-Taeg Lee, Sung-Kyu Park, Jong-Ho Won, Dae-Sik Hong, Hee-Sook Park
Cancer Research and Treatment.2006; 38(2): 72. CrossRef
Irinotecan, Continuous 5-Fluorouracil, and Low dose of Leucovorin (modified FOLFIRI) as First Line of Therapy in Recurrent or Metastatic Colorectal Cancer
Myung-Ah Lee, Jae-Ho Byun, Byoung-Young Shim, In-Sook Woo, Jin-Hyung Kang, Young Seon Hong, Kyung Shik Lee, Myung Gyu Choi, Suk Kyun Chang, Seong Taek Oh, Sung Il Choi, Doo Suk Lee
The Korean Journal of Internal Medicine.2005; 20(3): 205. CrossRef
Responsiveness of CPT-11 in Respect to hMLH1 and hMSH2 Protein Expression in the Primary Colorectal Cancer
In Ja Park, Hee Cheol Kim, Chang Sik Yu, Heung Moon Chang, Jea Hwan Lee, Jong Hoon Kim, Tae Won Kim, Jung Sun Kim, Jin Cheon Kim
Cancer Research and Treatment.2004; 36(6): 360. CrossRef

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Protracted Venous Infusion of 5-Fluorouracil as a Chemotherapy in Colorectal Cancer: Hyun Sik Jeong, Won Seog Kim, Sook In Jung, Jong Tae Lee, Ki Hyun Kim, Sung Soo Yoon, Won Ki Kang, Hong Ghi Lee, Ken Chil Park, Poong Lyul Rhee, Hae Jun Kim, Ho Kyun Chun, Chan Hyung Park; J Korean Cancer Assoc. 1999;31(1):120-125.

Abstract PDF: PURPOSE
The administration of 5-fluorouracil (5-FU) by protracted intravenous infusion is an alternative to the bolus administration of 5-FU in patients with advanced colorectal cancers. This study was performed to evaluate the response rate and toxicities of protracted infusion of 5-FU in patients with advanced or recurrent colorectal cancers who had been treated with 5-FU by bolus or shortterm continuous administration.
MATERIALS AND METHODS
Between March 1995 and June 1997, twenty-eight patients with advanced colorectal cancer previously exposed to 5-FU based chemotherapy were enrolled in this triaL Patients received 5-FU (250 mg/m(2)/day days 1-28) or 5-FU plus leucovorin (5-FU; 200 mg/m/day days 1-28, leucovorin; 20 mg/m IV days 1, 8, 15, 21) by ambulatory infusion pump. Treatment course was repeated every 42 days until disease progression.
RESULT
Twenty-eight patients entered. All 28 patients were assessable for response and toxicity. Five (19%) patients achieved a partial response, with the median response duration of 15 weeks (range; 7-22 weeks), and median survival time of entire patients was 54 weeks (range 7-151+ weeks). Gastrointestinal toxicity, specifically stomatitis was a major toxicity (grade 2, 12%; grade 3, 4%), but hand-foot syndrome was less frequent (5%) compared with other trials with protracted infusion of 5-FU reported in the literature. Hematologic toxicity was generally of low grade.
CONCLUSION
Prolonged intravenous infusion of 5-FU can produce a response rate of 19% with low toxicity among patients refractory to bolus or short-term infusion of S-FU.

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Treatment of Hepatic Metastasis of Colorectal Cancer: A Retrospective Analysis of the Outcome in 99 Patients: Jin Cheon Kim, Chang Nam Kim, Chang Sik Yu, Han Il Lee, Sang We Kim, Je Hwan Lee, Woo Kun Kim, Gyeong Hoon Kang, Moon Kyu Lee; J Korean Cancer Assoc. 1998;30(6):1175-1183.

Abstract PDF: PURPOSE
Among various modalities of treatment in hepatic metastasis of colorectal cancer, hepatic resection has been proven to be the most effective treatment. This analysis was intended to determine important prognostic parameters and to understand clinically significant factors during hepatic resection and follow-up period in patients with hepatic metastasis from colorectal cancer.
MATERIALS AND METHODS
Among 1,022 colorectal cancer patients treated at Asan Medical Center from July 1989 to December 1995, 99 patients were found to have liver metastasis at the time of first diagnosis or during follow-up period. These 99 patients were the subject of analysis in this retrospective clinical study. Surgical resection with curative intent was done in 35 patients and chemotherapy in 46 patients. Eighteen patients were with no treatment or misssed during follow-up. Survival rate was analysed according to clinicopathological parameters: sex, age, location of primary tumor, preoperative serum CEA level, TNM staging of primary tumor, number of hepatic metastasis, distribution, synchronous or metachronous lesions, diesase free interval, mode of treatment, type of resection, tumor free resection margin.
RESULTS
Overall survival of the patients with hepatic metastasis was significantly related with numbers of metastasis (<4 vs. >4), distribution (unilobar vs. bilobar), synchronous or metachronous lesions, disease free interval ( < 12 vs. > 12 months), mode of treatment (hepatic resection vs. chemotherapy vs, no treatment, p<0.01. A multivariate analysis showed a significant association of survival with mode of treatment (p<0.01). Survival of patients with hepatic resection was significantly related with resection margin (positive vs. < 1 cm vs. > 1 cm), TNM staging of primary tumor (II vs. III), number of hepatic metastasis (p<0.01), disease free interval (p<0.05). A multivariate analysis showed a significant correlation with survival for tumor free resection margin (p<0.01).
CONCLUSION
An aggressive approach of hepatic resection in the colorectal liver metastasis will improve survival, if the lesion pennits. In patients with hepatic resection, tumor free resection margin was the most important prognostic parameter by the uniand multivariate analysis. Therefore, every effort should be made to ensure that the clear margin be kept at least more than 1 cm during hepatic resection.

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Multiple Primary Malignant Neoplasm with Colorectal Cancer: Hee Chul Kim, Chang Nam Kim, Chun Sik Jung, Chang Sik Yu, Jin Cheon Kim; J Korean Cancer Assoc. 1998;30(4):668-674.

Abstract PDF: PURPOSE
The incidence of multiple primary malignant neoplasm has increased in recent decades. The etiologies and epidemiologies of multiple primary malignant neoplasm are still remained to be verified. A group of patients with multiple primary malignant neoplasms accompanied by colorectal cancer was analyzed to determine the relationship between certain cancers and colorectal cancer.
MATERIALS AND METHODS
From Jan. 1989 to Jun 1997, there were 56 patients with colorectal cancers accompanied by cancers of another organs. The retrospective analysis was done on the basis of cancer origin and intervals between the cancers.
RESULTS
The male-to-female ratio was 25 to 31. The characteristics of colorectal cancers in multiple primary malignant neoplasm were similar to the colorectal cancers without other cancers. Among 56 patients, 50 patients had the double primaries and 6 had the triple primaries. In the patients with double primaries, extracolonic cancers were found in the stomach(16), hepatobiliary system(12), urologic system(6), gynecologic organ(6) and others. In the patients with triple primaries, extracolic cancers were found in the stomach(5), uterus(2), lung(2) and others. The patients with family history of malignancy were 10 cases and the rate in the triple primaries seemed to be higher than double primaries.
CONCLUSION
It could be desirable to follow-up and work-up the patients with colorectal cancer keeping in mind that the malignancy in other organs especially stomach might be present.

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The Comparative Study between Peripharal Venous Blood and Draining Venous Blood CEA Levels in Colorectal Cancer: Kyung Bum Lee, Eun Sook Lee, Young Chul Kim; J Korean Cancer Assoc. 1998;30(2):306-312.

Abstract PDF: PURPOSE
In colon cancer, CEA(carcinoembryonic antigen) has become one of the useful tools for the management of patients because the antigen has been found to be useful as a monitor for detection, staging, recurrence, determining the response to therapy, and estimating the prognosis or survival. Many investigators have been analyzing the peripheral CEA levels for these purpose. Correlation between CEA levels of peripheral and portal blood, and histopathologic variables, was examined in 92 patients. This study evaluates importance of draining vein CEA levels in sensitivity and specificity of the prognosis.
MATERIALS AND METHODS
In 92 patients, comparison between peripheral and draining venous blood CEA levels was performed in order to get better sensitivity and specificity and precise prognosis of CEA in colorectal cancer. Stage, tumor site, tumor emboli, lymph nodes, ascitic fluid cytology and differentiations were considered.
RESULTS
There was no significant difference in peripheral and draining venous blood CEA levels in these variables. CEA positive rate of peripheral and draining vein were 57% and 60%. It has statistically no significance. More elevated CEA levels of draining vein than peripheral levels was detected in Duke C comparison (p=0.013). And more elevated CEA levels was observed in more advanced stages(33%, 59%, 63%, 83%) in draining vein(p < or = 0.01).
CONCLUSION
The prognosis of elevated CEA level in draining venous blood CEA levels in advanced stage is significant in prediction of patients prognosis and degree of advanced cancers.

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Microvessel Count and Overexpression of p53 in Early Colorectal Cancer: Young Min Kim, Gyeong Hoon Kang, Suk Kyun Yang, Chang Sik Yu, Jin Cheon Kim; J Korean Cancer Assoc. 1998;30(1):80-88.

Abstract PDF: PURPOSE
Angiogenesis, playing a critical role in tumor growth, development, and metastatic process, is alleged to be related to the prognostic factors and patient's survival of the colo-rectal cancer. The p53 gene, present in short arm of chromosome 17, is involved in multistep colo-rectal carcinogenesis. The correlation of p53 gene and angiogenesis has been recently reported. So, we designed to assess (1) the rate of p53 overexpression, (2) the prognostic significance of microvessel count, and (3) the relationship of p53 overexpression and angiogenesis in early colo-rectal cancer(ECC) patients. MATERIAL AND METHODS: The study material included 68 ECC from 65 patients, 40 mucosal (m-ECC) and 28 submucosal ECCs (sm-ECC). Immunostainings against p53 and factor VIII-related antigen were done and the results were analyzed with respect to tumor depth, site, and differentiation. And also the correlation between p53 overexpression and microvessel counts(MVC) was performed.
RESULT
The rate of p53 overexpression was higher in sm-ECC than in m-ECC (p < 0.05). The rate of p53 overexpression was highest in sigmoid colon and statistically significantly different compared with other sites. The differentiation of the tumor was closely correlated with p53 overexpression and the poorer the differentiation, the more overexpression of p53 (p<0.05). There was no significant difference between MVCs of m-ECC and sm-ECC (27.2+/-5.5 and 29.8 +/-6.0,respectively). However, MVC were higher in sigmoid colon than in any other sites (p<0.05). MVC did not show significant correlation with tumor differentiation or p53 overexpression.
CONCLUSION
These data indicate that p53 overexpression is correlated with tumor depth and differentiation but not MVC. The significance of higher MVC and p53 overexpression in sigmoid colon are reserved for further studies.

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Hepatic Intraarterial Chemotherapy in Unresectable Hepatic Metastases of Colorectal Cancer: Jin Cheon Kim, Han Il Lee, Chang Sik Yu, Hee Won Chung, Sang Wee Kim, Jeong Sin Lee, Kun Choon Park; J Korean Cancer Assoc. 1997;29(2):227-234.

Abstract PDF: PURPOSE
Unresectable hepatic metastases of colorectal cancer does not seem to be amenable to the various treatment modalities. We modified hepatic intraarterial chemotherapy by different installation of port and regimen.
MATERIALS AND METHODS
Between July 1989 to December 1995, 27 patients of colorectal cancer with unresectable liver metastases were randomly allocated into either hepatic intraarterial (HA, 11 patients) or systemic intravenous (IV, 16 patients) chemotherapy after primary tumor resection. Chemo-port was installed with preservation of hepatic arterial flow. One cycle of HA regimen included 5-fluorouracil (5-FU) and mitomycin-C (MMC) with or without leucovorin (LV) for 14 days every month. The IV regimen included 5-FU and LV for 5 days every month. Both HA and IV chemotherapy were continued from 6 to 12 cycles.
RESULTS
The response exceeding partial remission was experienced in six patients (55%) among 11 patients in the HA group, while only two (13%) patients showed response among sixteen patients in the IV group. One year survival was not different between two groups. Although lethal toxicity was not found, patients showed marked increase of the performance scale (ECOG) in both groups.
CONCLUSION
Although survival benefit was not prominent, higher response rate with tolerable complication was found in the HA group. Prudent selection of effective drugs and combination of systemic chemotherapy are needed to improve the survival with minimal complication.

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Prognostic Significance of p53 Protein Expression in Colorectal Cancer: Kang Choon Lee, Dong Wook Choi, Nan Mo Moon, Yong Kyu Kim, Nam Sun Paik, Jong Inn Lee, Dae Yong Hwang, Ja June Jang; J Korean Cancer Assoc. 1994;26(6):878-885.

Abstract PDF: Molecular carcinogenesis model in colorectal cancer was proposed by Vogelstein in 19B9, that is, the accumulation of a series of genetic alterations results in malignant transformation from normal epithelium. Among them, p 53 gene mutation is known to take place in late stage, and is detected in more than 70% of colorectal cancers. Also, it was suggested that genetic alteration of p53 gene was related to worse prognosis in colorectal cancer patients. On the other hand, it is controversial still now whether p53 oncoprotein expression have relation with poor prognosis in colorectal cancers or not. So, we studied the p53 protein expression in l39 case of colorectal cancer patients who underwent curative surgical resection in Korean Cancer Center Hospital from Jan. 1984 to Dec. 1988 with immunohistochemical technique using Pab 1801, which is monoclonal antibody to p53 protein. We also analyzed the relevance between p53 protein expression and the conventional prognostic parameters. The positive rate of p53 protein expression was 43.9%. We didn't find any relevance between positive p53 protein expression and the conventional prognostic parameters except significantly lower expression rate in mucinous carcinoma(p=0.02). And, we could not detect any prognostic significance of p53 protein expression in resectable colorectal cancer patients. In conclusion, nuclear p53 protein expression by immunohistochemistry is considered to have no prognostic impact in resectable colorectal cancer patients. and we suggest that further study shou1d be going on including multiple genetic alteraions, and cytoplasmic p53 protein expression to detect the factors influencing on prognosis.

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Leucovorin , 5-Fluorouracil and Cisplatin ( LV - FP ) Chemotherapy for Advanced Colorectal Cancer: Young Jin Yuh, Young Hyuck Im, Yoon Koo Kang, Bong Seog Kim, Hyung Gun Kim, Tae Yong Son, Sang Goo Lee, Eun Mee Cheon, You Cheoul Kim, Chang Min Kim, Weon Seon Hong, Jhin Oh Lee, Tae Woong Kang; J Korean Cancer Assoc. 1995;27(1):44-52.

Abstract PDF: The biochemical modulation of 5-fluorouracil(5-FU) by leucovorin has been demonstrated to enhance the activity of 5-FU in patients with advanced colorectal cancer and the synergism between 5-FU and cisplatin is well known in advanced gastrointestinal tract cancers. We conducted a phase II trial to evaluate the effect of a combination of leucovorin, 5-FU, and cisplatin(LV-FP) in patients with advanced colorectal cancer. LV-FP regimen consisted of leu- covorin 20 mg/m/day IV in day 1-5, 5-FU 1,000 mg/m/day continuous IV. infusion in day 1-5, and cisplatin 20 mg/m/day IV in day 1-5. The regimen was repeated every 3 weeks. Among 46 patients with histologically confirmed advanced colorectal adenocarcinoma, 31 patients had measurable lesion(s) with median age of 55 years(22-70 years). 27 patients had previous histo- ry of chemotherapy and l9 were previously untreated. There was no complete respanse. 11 patients responded partially to the regimen to make the response rate 35%(l1/31). The median time to progression was 16 weeks (2-44 weeks), and the median survival time was 42 weeks(l+~80 weeks). There was no difference in response rates between the previously treated and the previously untreated. Hematologic toxicities were mild and non-hematologic toxicities were also tolerable. There was no treatment-related mortality. These results indicate that the LV-FP regimen is safe and effective in advanced colorectal adenocarcinoma.

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Assessment of Cell Proliferation in Primary and Recurrent Colorectal Cancers - Expression of Transforming Growth Factor - α and Prolifer: Jin Sil Seong, Sun Hee Sung, Jung Woon Lee, Hyun Soo Shin, Charn Il Park, Oh Hun Kwon; J Korean Cancer Assoc. 1995;27(2):223-230.

Abstract PDF: Cell proliferation potential has been found to be a significant biological parameter correlated with the clinical outcome. This study was ta investigate the cell proliferation potential in primary and recurrent colorectal tumor tissues. Using paraffin-embedded tissues from the paired primary and recurrent tumors of l0 patients, a simple hematoxylineosin stain was done and immunohistochemical stains for trans- forming growth factor-a(TGF-a) and proliferating cell nuclear antigen(PCNA) were performed through a labeled streptavidine biotin method. DNA contents and S-phase fraction(SPF) of the cells were assessed by flowcytometric DNA analysis. The degree of differentiation was poorer in the recurrent tumors than in primary tumors. In 4 primary tumors with mixed adenocacinoma and mucinous adenocarcinoma, only the mucinous adenocarcinoma companent was shown in the recurrent tumors. There was no difference in TGF-a expression between the primary and the recurrent tumors however, PCNA was overexpressed in the recurrent tumors comparing to the primary tumors. Flow cytometric DNA analysis was successful in 7 paired cases. There was change of the ploidy from the diploidy to the aneuploidy in 4 cases. SPF showed remarkable increase in the recurrent tumors comparing to the primary tumors. These results show high proliferative potential of the recurrent colorectal tumors, which can be measured using PCNA expression and SPF as biomarkers. Based on the results of this study, an effort to establish more refined method to predict recurrence should be pursued.

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Expression and Significance of c-erbB-2 in Radically Resected Colorectal Cancer: Hyun Cheol Chung, Sun Young Rha, Joon Oh Park, Seung Hun Song, Jae Yong Cho, Jung Bae Aha, Hye Ran Lee, Chong In Lee, Nae Choon Yoo, Joo Hang Kim, Jae Kyung Roh, Jin Sil Seong, Gwi Eon Kim, Jin Sik M; J Korean Cancer Assoc. 1995;27(3):389-403.

Abstract PDF: Overexpression of c-erbB-2 oncoprotein has been shown to correlate with poor prognosis and drug-resistance to the conventional chemotherapy with 5-fluorouracil in breast and gastric cancers. To evaluate the clinical significance of c-erbB-2 overexpreseion in colorectal cancer, immunohistochemical staining was performed with the paraffin-embedded tiasues of 141 colorectal cancer patients with curative surgery. The follow-up duration ranged from 7 to 61 months(median 30 months). Two-year disease- free and overall survival rate of the total patients were 77%, 91%, respectively. The c-erbB-2 positive rate was 24.8%, Even if patients with c-erbB-2 overexpression showed a tendency of poor prognosis than c-erbB-2 negative patients, T-factor and the TNM stage were independent prognostic factors in multivariate analysis. In subset analysis with c-erbB-2 negative patienta, there were no differences in recurrence rate and 2-year disease-free survival rate between pa- tients with chemotherapy and without chemotherapy(20.0% versus 26.1%)(80.0% versus 82.0%). However, in c-erbB-2 positive patients, those subgroup with chemotherapy showed tendencies toward advantages in relapse rate and 2-year disease-free survival rate than those of subgroup without chemotherapy(21.0% versus 50.0%; p=0.09)(76.0% versus 50.0%: p=0.06). Also, there was a tendency of increased time to relapse in patients with chemotherapy comparing to that of the patients without chemotherapy(7.5 months versus l7.0 months; p = 0.09). In stage III, patients with c-erbB-2 overexpression showed increased 2-year disease-free survival rate with chemotherapy as comparing to that of patients without chemotherapy(81.0% versus 29.0%; p= 0.003). Again, this survival benefit was not found in c-erbB-2 negative stage III patients regard- less of chemotherapy. In conclusion, c-erbB-2 overexyression might be a marker of relative drug resistance to 5-FU which will be converted with the high dose treatment of modulation with leucovorin. A prospective randomized trial is warrented to confirm this suggestion and for the clinical applica- tion of c-erbB-2 overexpression.

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The Effect of Perioperative Blood Transfusion on the Prognosis of Colorectal Cancer Patients: Hee Jung Choi, Jin Hyuk Choi, Soon Nam Lee, Eung Bum Park, Kyung Ja Lee; J Korean Cancer Assoc. 1995;27(3):403-411.

Abstract PDF: Except for the weli known prognostic factors of cancer, the studies that perioperative transfusion of surgically resectable cancer could influence the survival of cancer patients were continued to be investigated. The explanation of deleterious effects of transfusion has been supported by the results that the incidences of renal allograft rejection were decreased by pretransplantation tranafusion, and transfusion resulted in changes of mononuclear cell function and inhibited natural killer cell activity. But definite proof of this adverse eifect has not been settled. We investigated whether perioperative transfusion can diminish the eurvival rate of patients with colorectal cancer and transfusion itself can become prognostic factor by way of retrospec- tive analysis of 104 surgically resected colorectal cancer patients. Five year survival rate of 46.2% in transfusion group(n=53) is significantly decreased compared with the rate of 73.8% in non-transfusion group(n=51) (P<0.05). In subgroup analysis, there is no difference in survival rate by stage, the amount and component of blood transfusion. There are many other variables that can affect survival rate of cancer patient except for transfusion, multivariate Cox regression analysis was performed. The tumor differentiation is the greatest relative risk, but transfusion itself is not an independent prognostic value. In conclusion, perioperative transfusion and the swvival rate did not show direct relationship in these surgically resected coiorectal cancer patients. Nevertheless the difference in survival rate between transfusion group and non-transfusion group is significant, judicious use of blood products, use of frozen washed red blood cells that are totally lacking in white cells might be necessary. To confirm the direct causal relationship between perioperative transfusion and the survival in colorectal cancer, the larger prospective investigations are thought to be needed.

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Lymph Node Micrometastases from Dukes'B Colorectal Cacner : Immunohistochemical detection , and prognostic significance: Kwan Sik Lee, Il Woo Whang, Mae Ja Park, Ik Soo Kim, In Soo Suh, Soo Han Jun; J Korean Cancer Assoc. 1996;28(1):43-50.

Abstract PDF: This study was performed to identify micrometastases in lymph nodes from colorectal cancer considered free of disease by the routine hematoxylin-eosin stain, using immunohistochemistry according to ABC method. All 993 lymph nodes from 56 patients with Dukes'B colorectal cancer were stained retrospectively with antibody against cytokeratin(antikeratin AEl/AE3, Boeringer Mannheim). Single tumor cells and small clusters of tumor cells were detected in nodes of 20 patients(35.7%), mainly in the subcapsular sinuses. Twenty nine of the 36 patients with cytokeratin-negative lymph nodes lived after a mean followup of 55 months. But, 8 of the 20 patients with cytokeratin-positive lymph nodes lived over the same time period. Multivariate analyses were performed with several prognostic factors: age, histologic differentiation, vascular and lymphatic invasion, and presence of micrometastases. The most significant factor for both survival and recurrence was the presence of micrometastases(P= 0.0403 and P=0.0364 respectively). The presence of cytokeratin-positive cells within lymph nodes of Dukes'B colorectal cancer correlated with a poor prognosis.

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Hereditary Nonpolyposis Colorectal Cancer in Korean: Jae Hwan Oh, Hye Jung Han, Ja Lok Ku, Yuan Ying, Kwang Yun Kim, Kwang Yun Kim, Sung Kim, Young Jin Kim, Chung Yong Kim, Jin Cheon Kim, Jin Cheon Kim, Nam Geun Oh, Choong Yoon, Kee Hyung Lee, Kuk Jin Cho; J Korean Cancer Assoc. 1996;28(2):207-215.

Abstract PDF: Hereditaty nonpolyposis colon cancer (HNPCC) accounts for about 5% of all colorectal cancer. Mutations in the DNA mismatch repair genes (hMLH1, hMSH2 and PMS families) are responsible to HNPCC. To study the characteristics and optimal treatment modality of Korean HNPCC patients, we analysed the 29 HNPCC families registered in the Korean Hereditary Colorectal Cancer Registry. The control group consisted of 791 colorectal cancer patients treated in Seoul National University Hospital between 199I and 1994. Twenty-nine HNPCC families included 116 (79 males and 37 females) colorectal cancer patients. Following findings were significantly different from those of control group. ¨c Their average age at diagnosis was younger (44 years) than that of control group (56 years). ¨e Thirty-nine percent of colorectal cancer were located proximal to splenic flexure compared to 24% of cantrol group. ¨e Fifty percent of cancers located in sigmoid colon or rectum, but in control group 73% of cancers located in those area. In Western series, however, only 23.3% of cancers located in the sigmoid colon or rectum. Operative and pathologic records were available from 45 HNPCC patients. Forty-four percent of those 45 HNPCC patients had multiple colorectal cancers including polyps. Thirty-eight percent of HNPCC Patients had the tumors in both sides of the large bowel. Forty-five patients received 52 operations, but only 13 cases (25% ) were total or subtotal colectomy. Endometrial cancer and stomach cancer were the most frequent extracolonic cancers in HNPCC. HNPCC should be suspected in colorectal cancer patients with early age of onset and proximal colon involvement, or multiple colorectal cancers. We confirmed that the extent of the resection for HNPCC patients should be more than subtotal colectomy. Screening for endometrial and stomach cancer was necessary in families with those cancers. Especially woman with HNPCC should be considered hysterectomy and bilateral salpingo-oophorectomy at the time of colectomy.

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