Cancer Research and Treatment

Original Articles

Concept of Depth of Invasion Can Improve Staging Performance in Patients with Resected Distal Cholangiocarcinoma: Validation of the American Joint Committee on Cancer Staging System: Won-Gun Yun, Yoon Soo Chae, Youngmin Han, Young Jae Cho, Hye-Sol Jung, Wooil Kwon, Joon Seong Park, Haeryoung Kim, Kyoung Bun Lee, Jin-Young Jang; Received April 12, 2025 Accepted August 22, 2025 Published online August 25, 2025; DOI: https://doi.org/10.4143/crt.2025.406 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Purpose
The American Joint Committee on Cancer (AJCC) staging system for distal cholangiocarcinoma (dCC) has evolved significantly. However, the prognostic correlation of the newly proposed staging system remains unclear. Therefore, we aimed to compare the staging performance between AJCC 7th and 8th editions for dCC.
Materials and Methods
We reviewed pathological slides of consecutive patients who underwent resection for dCC between 2000 and 2022. According to the AJCC 8th edition, depth of invasion was defined as the distance from the basement membrane of adjacent normal or dysplastic epithelium to the deepest tumor invasion. We analyzed changes in the T category from the AJCC 7th to 8th edition and assessed overall survival and recurrence based on these staging systems.
Results
Among 428 patients, application of the 8th edition resulted in down-staging of 272 (63.6%) patients and up-staging of only 13 (3.0%). Lymph node metastases were identified in 150 (35.1%) patients, with 29 (6.8%) having ≥ 4 metastatic nodes. The C-indices for overall survival and recurrence are 0.557 and 0.569 for the T category of the AJCC 7th edition, and 0.606 and 0.631 for that of the AJCC 8th edition (95% confidence interval for delta, 0.005 to 0.092 for survival, 0.023 to 0.100 for recurrence). Additionally, the T category of the 8th edition correlated more strongly with lymph node metastases than that of the 7th edition.
Conclusion
In dCC, the T category of the AJCC 8th edition demonstrates improved prognostic correlation and better alignment with lymph node metastases compared to that of the 7th edition.

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Gastrointestinal Cancer

Phase II Trial of Postoperative Adjuvant Gemcitabine and Cisplatin Chemotherapy Followed by Chemoradiotherapy with Gemcitabine in Patients with Resected Pancreatic Cancer: Kyung-Hun Lee, Eui Kyu Chie, Seock-Ah Im, Jee Hyun Kim, Jihyun Kwon, Sae-Won Han, Do-Youn Oh, Jin-Young Jang, Jae-Sung Kim, Tae-You Kim, Yung-Jue Bang, Sun Whe Kim, Sung W. Ha; Cancer Res Treat. 2021;53(4):1096-1103. Published online December 30, 2020; DOI: https://doi.org/10.4143/crt.2020.928

Purpose
Despite curative resection, the 5-year survival for patients with resectable pancreatic cancer is less than 20%. Recurrence occurs both locally and at distant sites and effective multimodality adjuvant treatment is needed.
Materials and Methods
Patients with curatively resected stage IB-IIB pancreatic adenocarcinoma were eligible. Treatment consisted of chemotherapy with gemcitabine 1,000 mg/m² on days 1 and 8 and cisplatin 60 mg/m² on day 1 every 3 weeks for two cycles, followed by chemoradiotherapy (50.4 Gy/28 fx) with weekly gemcitabine (300 mg/m²/wk), and then gemcitabine 1,000 mg/m² on days 1 and 8 every 3 weeks for four cycles. The primary endpoint was 1-year disease-free survival rate. The secondary endpoints were disease-free survival, overall survival, and safety.
Results
Seventy-four patients were enrolled. One-year disease-free survival rate was 57.9%. Median disease-free and overall survival were 15.0 months (95% confidence interval [CI], 11.6 to 18.4) and 33.0 months (95% CI, 21.8 to 44.2), respectively. At the median follow-up of 32 months, 57 patients (77.0%) had recurrence including 11 patients whose recurrence was during the adjuvant treatment. Most of the recurrences were systemic (52 patients). Stage at the time of diagnosis (70.0% in IIA, 51.2% in IIB, p=0.006) were significantly related with 1-year disease-free survival rate. Toxicities were generally tolerable, with 53 events of grade 3 or 4 hematologic toxicity and four patients with febrile neutropenia.
Conclusion
Adjuvant gemcitabine and cisplatin chemotherapy followed by chemoradiotherapy with gemcitabine and maintenance gemcitabine showed efficacy and good tolerability in curatively resected pancreatic cancer.

Citations

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Impact of chemotherapy dose capping on treatment intensity and survival in early breast cancer patients with high body surface area
A. Englisch, K. Eissler, D. Dannehl, J. Englisch, A. D. Hartkopf, S. Y. Brucker, E. M. Grischke, L. L. Volmer, T. Engler
Archives of Gynecology and Obstetrics.2026;[Epub] CrossRef
The adverse prognostic impact of reduced chemotherapy dose intensity appears attenuated in early breast cancer patients with treatment-relevant neutropenia: a retrospective cohort study
K. Eissler, T. Engler, D. Dannehl, B. Schönfisch, J. Englisch, A. D. Hartkopf, S. Y. Brucker, E. M. Grischke, L. L. Volmer, Alexander Englisch
Archives of Gynecology and Obstetrics.2026;[Epub] CrossRef
NUDT21 interacts with NDUFS2 to activate the PI3K/AKT pathway and promotes pancreatic cancer pathogenesis
Xiao-Dong Huang, Yong-Wei Chen, Lv Tian, Li Du, Xiao-Chen Cheng, Yu-Xin Lu, Dong-Dong Lin, Feng-Jun Xiao
Journal of Cancer Research and Clinical Oncology.2024;[Epub] CrossRef
Efficacy of Cisplatin-Containing Chemotherapy Regimens in Patients of Pancreatic Ductal Adenocarcinoma: A Systematic Review and Meta-analysis
Obaid Ur Rehman, Eeshal Fatima, Zain Ali Nadeem, Arish Azeem, Jatin Motwani, Habiba Imran, Hadia Mehboob, Alishba Khan, Omer Usman
Journal of Gastrointestinal Cancer.2024; 55(2): 559. CrossRef
OTUB1/NDUFS2 axis promotes pancreatic tumorigenesis through protecting against mitochondrial cell death
Xiao-Dong Huang, Li Du, Xiao-Chen Cheng, Yu-Xin Lu, Qiao-Wei Liu, Yi-Wu Wang, Ya-Jin Liao, Dong-Dong Lin, Feng-Jun Xiao
Cell Death Discovery.2024;[Epub] CrossRef
Impact of obesity on pathological complete remission in early stage breast cancer patients after neoadjuvant chemotherapy: a retrospective study from a German University breast center
Johannes Felix Englisch, Alexander Englisch, Dominik Dannehl, Kenneth Eissler, Christian Martin Tegeler, Sabine Matovina, Léa Louise Volmer, Diethelm Wallwiener, Sara Y. Brucker, Andreas Hartkopf, Tobias Engler
Archives of Gynecology and Obstetrics.2024; 311(2): 437. CrossRef
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Chunhong Sui, Yijia Luo, Xiao Xiao, Jiaxue Liu, Xiaotong Shao, Yingxue Xue, Cheng Wang, Wenliang Li
ChemistrySelect.2023;[Epub] CrossRef
Ivermectin and gemcitabine combination treatment induces apoptosis of pancreatic cancer cells via mitochondrial dysfunction
Da Eun Lee, Hyeon Woong Kang, So Yi Kim, Myeong Jin Kim, Jae Woong Jeong, Woosol Chris Hong, Sungsoon Fang, Hyung Sun Kim, Yun Sun Lee, Hyo Jung Kim, Joon Seong Park
Frontiers in Pharmacology.2022;[Epub] CrossRef
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Yeting Lu, Shuping Zhou, Gong Cheng, Yi Ruan, Yuan Tian, Kaiji Lv, Shuo Han, Xinhua Zhou, Xiangya Ding
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媛媛苏
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Zebrafish Patient-Derived Xenografts Identify Chemo-Response in Pancreatic Ductal Adenocarcinoma Patients
Alice Usai, Gregorio Di Franco, Margherita Piccardi, Perla Cateni, Luca Emanuele Pollina, Caterina Vivaldi, Enrico Vasile, Niccola Funel, Matteo Palmeri, Luciana Dente, Alfredo Falcone, Dimitri Giunchi, Alessandro Massolo, Vittoria Raffa, Luca Morelli
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Peng Chen, Zhiwei He, Jie Wang, Jian Xu, Xueyi Jiang, Yankun Chen, Xinyuan Liu, Jianxin Jiang
Frontiers in Cell and Developmental Biology.2021;[Epub] CrossRef

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Validation of the 8th AJCC Cancer Staging System for Pancreas Neuroendocrine Tumors Using Korean Nationwide Surgery Database: Yunghun You, Jin-Young Jang, Song Cheol Kim, Yoo-Seok Yoon, Joon Seong Park, Chol Kyoon Cho, Sang-Jae Park, Jae Do Yang, Woo Jung Lee, Tae Ho Hong, Keun Soo Ahn, Chi-Young Jeong, Hyeon Kook Lee, Seung Eun Lee, Young Hoon Roh, Hee Joon Kim, Hongbeom Kim, In Woong Han; Cancer Res Treat. 2019;51(4):1639-1652. Published online April 19, 2019; DOI: https://doi.org/10.4143/crt.2019.023

Abstract PDF PubReader ePub

Purpose
The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for pancreatic neuroendocrine tumor (PNET) included several significant changes. We aim to evaluate this staging system compared to the 7th edition AJCC staging system and European Neuroendocrine Tumors Society (ENETS) system.
Materials and Methods
We used Korean nationwide surgery database (2000-2014). Of 972 patients who had undergone surgery for PNET, excluding patients diagnosed with ENETS/World Health Organization 2010 grade 3 (G3), only 472 patients with accurate stage were included.
Results
Poor discrimination in overall survival rate (OSR) was noted between AJCC 8th stage III and IV (p=0.180). The disease-free survival (DFS) curves of 8th AJCC classification were well separated between all stages. Compared with stage I, the hazard ratio of II, III, and IV was 3.808, 13.928, and 30.618, respectively (p=0.007, p < 0.001, and p < 0.001). The curves of OSR and DFS of certain prognostic group in AJCC 7th and ENETS overlapped. In ENETS staging system, no significant difference in DFS between stage IIB versus IIIA (p=0.909) and IIIA versus IIIB (p=0.291). In multivariable analysis, lymphovascular invasion (p=0.002), perineural invasion (p=0.003), and grade (p < 0.001) were identified as independent prognostic factors for DFS.
Conclusion
This is the first large-scale validation of the AJCC 8th edition staging system for PNET. The revised 8th system provides better discrimination compared to that of the 7th edition and ENETS TNM system. This supports the clinical use of the system.

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Trends in Gallbladder Cancer Incidence and Survival in Korea: Youngjun Wi, Hyeongtaek Woo, Young-Joo Won, Jin-Young Jang, Aesun Shin; Cancer Res Treat. 2018;50(4):1444-1451. Published online January 24, 2018; DOI: https://doi.org/10.4143/crt.2017.279

Abstract PDF Supplementary Material PubReader ePub

Purpose
The current study was undertaken to examine the trend in gallbladder cancer (GBC) incidence and survival in Korea.
Materials and Methods
GBC incidence data by histologic typewere obtained from the Korea Central Cancer Registry. Age-standardized incidence rates were calculated using the mid-year Korean population of 2000 as a standard population, and a joinpoint regression model was used to calculate the annual percent change (APC) in incidence rates. Incidence by Surveillance, Epidemiology and End Results (SEER) summary stage and by geographical areas and female-to-male incidence rate ratios was also described.
Results
The number of new GBC cases increased between 1999 and 2013. Nevertheless, the agestandardized incidence rate decreased by 0.5% per year in men (p < 0.01), whereas the incidence rate in women did not change significantly over the same period (APC, –0.2; p=0.6). The most common histologic type was adenocarcinoma in both sexes. Based on the SEER stage, the distant stage was the most frequent stage (41%), followed by the regional stage (37%). Ulsan (4.31/100,000 for men and 4.09/100,000 forwomen in 2009- 2013) and Gyeongsangnam-do (4.15/100,000 for men and 3.54/100,000 for women) showed the highest GBC incidence, whereas the lowest incidence was observed in Seoul and Gyeonggi-do. There were no significant sex differences in the incidence of GBC (femaleto-male incidence rate ratio, 0.96).
Conclusion
The overall incidence of GBC in Korea did not change significantly over the 15-year period. Incidence for men and women was similar. However, geographical variation was found.

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Long-Term Outcome of Distal Cholangiocarcinoma after Pancreaticoduodenectomy Followed by Adjuvant Chemoradiotherapy: A 15-Year Experience in a Single Institution: Byoung Hyuck Kim, Kyubo Kim, Eui Kyu Chie, Jeanny Kwon, Jin-Young Jang, Sun Whe Kim, Do-Youn Oh, Yung-Jue Bang; Cancer Res Treat. 2017;49(2):473-483. Published online August 23, 2016; DOI: https://doi.org/10.4143/crt.2016.166

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study was conducted to evaluate the long-term outcome in patients undergoing pancreaticoduodenectomy (PD) followed by adjuvant chemoradiotherapy for distal cholangiocarcinoma (DCC) in a high-volume center and to identify the prognostic impact of clinicopathologic factors.
Materials and Methods
A total of 132 consecutive patients who met the inclusion criteria were retrieved from the institutional database from January 1995 to September 2009. All patients received adjuvant treatments at a median of 45 days after the surgery. Median follow-up duration was 57 months (range, 6 to 225 months) for all patients and 105 months for survivors (range, 13 to 225 months).
Results
The 5-year locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) rates were 70.7%, 55.7%, 49.4%, and 48.1%, respectively. Univariate analysis revealed poorly differentiated (P/D) tumors and lymph node (LN) metastasis were significantly associated with DMFS and OS. Additionally, preoperative carbohydrate antigen 19-9 level was significantly correlated with DFS, LRRFS, and DMFS. Upon multivariate analysis for OS, P/D tumors (p=0.015) and LN metastasis (p=0.003) were significant prognosticators that predicted inferior OS. Grade 3 or higher late gastrointestinal toxicity occurred in only one patient (0.8%).
Conclusion
Adjuvant chemoradiotherapy after PD for DCC is an effective and tolerable strategy without significant side effects. During long-term follow-up, we found that prognosis of DCC was mainly influenced by histologic differentiation and LN metastasis. For patients with these risk factors, further research should focus on improving adjuvant strategies as well as other treatment approaches.

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Prognostic Value of Splenic Artery Invasion in Patients Undergoing Adjuvant Chemoradiotherapy after Distal Pancreatectomy for Pancreatic Adenocarcinoma: Byoung Hyuck Kim, Kyubo Kim, Eui Kyu Chie, Jin-Young Jang, Sun Whe Kim, Sae-Won Han, Do-Youn Oh, Seock-Ah Im, Tae-You Kim, Yung-Jue Bang, Ijin Joo, Sung W. Ha; Cancer Res Treat. 2015;47(2):274-281. Published online September 12, 2014; DOI: https://doi.org/10.4143/crt.2014.025

Abstract PDF PubReader ePub

Purpose
The purpose of this study was to evaluate the outcome of adjuvant chemoradiotherapy (CRT) after distal pancreatectomy (DP) in patients with pancreatic adenocarcinoma, and to identify the prognostic factors for these patients.
Materials and Methods
We performed a retrospective review of 62 consecutive patients who underwent curative DP followed by adjuvant CRT between 2000 and 2011. There were 31 men and 31 women, and the median age was 64 years (range, 38 to 80 years). Adjuvant radiotherapy was delivered to the tumor bed and regional lymph nodes with a median dose of 50.4 Gy (range, 40 to 55.8 Gy). All patients received concomitant chemotherapy, and 53 patients (85.5%) also received maintenance chemotherapy. The median follow-up period was 24 months.
Results
Forty patients (64.5%) experienced relapse. Isolated locoregional recurrence developed in 5 patients (8.1%) and distant metastasis in 35 patients (56.5%), of whom 13 had both locoregional recurrence and distant metastasis. The median overall survival (OS) and disease-free survival (DFS) were 37.5 months and 15.4 months, respectively. On multivariate analysis, splenic artery (SA) invasion (p=0.0186) and resection margin (RM) involvement (p=0.0004) were identified as significant adverse prognosticators for DFS. Also, male gender (p=0.0325) and RM involvement (p=0.0007) were associated with a significantly poor OS. Grade 3 or higher hematologic and gastrointestinal toxicities occurred in 22.6% and 4.8% of patients, respectively.
Conclusion
Adjuvant CRT may improve survival after DP for pancreatic body or tail adenocarcinoma. Our results indicated that SA invasion was a significant factor predicting inferior DFS, as was RM involvement. When SA invasion is identified preoperatively, neoadjuvant treatment may be considered.

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Journal of Gastrointestinal Surgery.2015; 19(12): 2183. CrossRef

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