Cancer Research and Treatment

Original Articles

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.

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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
CircLMTK2 Silencing Attenuates Gemcitabine Resistance in Pancreatic Cancer by Sponging miR-485-5p and to Target PAK1
Yeting Lu, Shuping Zhou, Gong Cheng, Yi Ruan, Yuan Tian, Kaiji Lv, Shuo Han, Xinhua Zhou, Xiangya Ding
Journal of Oncology.2022; 2022: 1. CrossRef
Effects of Radiotherapy and Chemotherapy on Postoperative Prognosis of Patients Undergoing Radical Surgery for Pancreatic Cancer—Based on SEER Database Analysis
媛媛苏
Advances in Clinical Medicine.2022; 12(10): 9540. CrossRef
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
Cancers.2021; 13(16): 4131. CrossRef
Hypoxia-Induced ZWINT Mediates Pancreatic Cancer Proliferation by Interacting With p53/p21
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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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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Proposal for Risk-Adjusted Surveillance Strategies in Extrahepatic Bile Duct Cancer with Cost-Effectiveness Validation: A Real-World Multi-institutional Cohort Analysis
Jae Sik Kim, Jinsil Seong, Kyubo Kim, Jeong Il Yu, Wonguen Jung, Tae Hyun Kim, Woo Chul Kim, Jin Hwa Choi, Ah Ram Chang, Younghee Park, Bae Kwon Jeong, Byoung Hyuck Kim, Tae Gyu Kim, Jin Hee Kim, Hae Jin Park, Hyun Soo Shin, Jung Ho Im, Eui Kyu Chie
International Journal of Radiation Oncology*Biology*Physics.2026; 125(5): 1445. CrossRef
Analysis of Risk Factors for Recurrence of Distal Bile Duct Cancer without Lymph Node Metastasis after Curative Resection: Is Adjuvant Therapy Really Required?
So Jeong Kim, Hee Seung Lee, Moon Jae Chung, Jeong Youp Park, Seung Woo Park, Seungmin Bang
Journal of Digestive Cancer Research.2026; 14(1): 43. CrossRef
Surgical Considerations for Biliary and Perihilar Neoplasms
Lily V. Saadat, William R. Jarnagin
Hematology/Oncology Clinics of North America.2026; 40(4): 521. CrossRef
Real-World Application of a Machine Learning-Based Early Recurrence Model for Guiding Adjuvant Chemotherapy Use in Patients with Gallbladder Cancer
Won-Gun Yun, Youngmin Han, Yoon Soo Chae, Young Jae Cho, Hye-Sol Jung, Joon Seong Park, Jin-Young Jang, Wooil Kwon
Gut and Liver.2026; 20(4): 694. CrossRef
Patterns, timing and predictors of recurrence following pancreaticoduodenectomy for distal cholangiocarcinoma: An international multicentre retrospective cohort study
Peter LZ. Labib, Thomas B. Russell, Jemimah L. Denson, Mark A. Puckett, Fabio Ausania, Elizabeth Pando, Keith J. Roberts, Ambareen Kausar, Vasileios K. Mavroeidis, Ricky H. Bhogal, Gabriele Marangoni, Sarah C. Thomasset, Adam E. Frampton, Duncan R. Spaldi
European Journal of Surgical Oncology.2024; 50(6): 108353. CrossRef
Liver Transplantation for Cholangiocarcinoma
Nadine Soliman, Ashton A. Connor, Sudha Kodali, Rafik Mark Ghobrial
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Durable Response to Pembrolizumab and Lenvatinib in a Patient with Chemotherapy-refractory Cholangiocarcinoma
Winn Soe P, Huang Yiwu
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Impact of adjuvant therapy on outcomes after curative‐intent resection for distal cholangiocarcinoma
Jing‐Jing Hou, Shishir K. Maithel, Sharon M. Weber, George Poultsides, Christopher L. Wolfgang, Ryan C. Fields, Jin He, Charles Scoggins, Kamron Idrees, Perry Shen, Xu‐Feng Zhang, Timothy M. Pawlik
Journal of Surgical Oncology.2023; 127(4): 607. CrossRef
The short- and long-term outcomes of pancreaticoduodenectomy for distal cholangiocarcinoma
Pavel Skalicky, Ondrej Urban, Jiri Ehrmann, Hana Svebisova, Dusan Klos, Jana Tesarikova, Cestmir Neoral, Katerina Knapkova, Martin Lovecek
Biomedical Papers.2022; 166(4): 386. CrossRef
Patterns of Regional Failure after Pancreaticoduodenectomy in Patients with Distal Extrahepatic Cholangiocarcinoma: Suggestion of the Clinical Target Volume for Elective Nodal Irradiation
W. Jung, Y. Park, K. Kim, H.J. Park, B.H. Kim
Clinical Oncology.2022; 34(1): e45. CrossRef
Pathological, molecular, and clinical characteristics of cholangiocarcinoma: A comprehensive review
Mukul Vij, Yogesh Puri, Ashwin Rammohan, Gowripriya G, Rajesh Rajalingam, Ilankumaran Kaliamoorthy, Mohamed Rela
World Journal of Gastrointestinal Oncology.2022; 14(3): 607. CrossRef
The prognostic value of the lymph node ratio in patients with distal cholangiocarcinoma after curative intended surgery: A single-center retrospective study
Chaeyung Oh, Hee Joon Kim, Sang Hwa Song, Eun Kyu Park, Young Hoe Hur, Yang Seok Koh, Chol Kyoon Cho
Annals of Hepato-Biliary-Pancreatic Surgery.2022; 26(2): 168. CrossRef
Etiology, Clinical Presentations, and Short-Term Treatment Outcomes of Extrahepatic Obstructive Jaundice in South-Western Uganda
Charles Newton Odongo, Carlos Cabrera Dreque, David Mutiibwa, Felix Bongomin, Felix Oyania, Mvuyo Maqhawe Sikhondze, Moses Acan, Raymond Atwine, Fred Kirya, Martin Situma
Clinical and Experimental Gastroenterology.2022; Volume 15: 79. CrossRef
Lymph Node Ratio Nomogram-Based Prognostic Model for Resected Distal Cholangiocarcinoma
Marc Perez, Carsten Palnaes Hansen, Fernando Burdio, Gianluca Pellino, Adolfo Pisanu, Roberto Salvia, Marcello Di Martino, Mohammad Abu Hilal, Luca Aldrighetti, Benedetto Ielpo
Journal of the American College of Surgeons.2022; 235(5): 703. CrossRef
Surgical management of biliary malignancy
T. Peter Kingham, Victoria G. Aveson, Alice C. Wei, Jason A. Castellanos, Peter J. Allen, Daniel P. Nussbaum, Yinin Hu, Michael I. D'Angelica
Current Problems in Surgery.2021; 58(2): 100854. CrossRef
Survival benefit with adjuvant radiotherapy after resection of distal cholangiocarcinoma: A propensity‐matched National Cancer Database analysis
Sivesh K. Kamarajah, Filip Bednar, Clifford S. Cho, Hari Nathan
Cancer.2021; 127(8): 1266. CrossRef
Re-appraising the role of lymph node status in predicting survival in resected distal cholangiocarcinoma – A meta-analysis and systematic review
Ken Min Chin, Marcello Di Martino, Nicholas Syn, Benedetto Ielpo, Mohammad Abu Hilal, Brian K.P. Goh, Ye Xin Koh, Mikel Prieto
European Journal of Surgical Oncology.2021; 47(6): 1267. CrossRef
The Role of Adjuvant Chemoradiotherapy in Nonhilar Extrahepatic Bile Duct Cancer: A Long-Term Single-Institution Analysis
Won Ick Chang, Byoung Hyuck Kim, Hyun-Cheol Kang, Kyubo Kim, Kyung-Hun Lee, Do-Youn Oh, Hongbeom Kim, Wooil Kwon, Jin-Young Jang, Eui Kyu Chie
International Journal of Radiation Oncology*Biology*Physics.2021; 111(2): 395. CrossRef
Differences in Prognostic Factors and Recurrence Patterns After Curative-Intent Resection of Perihilar and Distal Cholangiocarcinomas
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Prognostic factors and patterns of recurrence after curative resection for patients with distal cholangiocarcinoma
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Proposed Modification of Staging for Distal Cholangiocarcinoma Based on the Lymph Node Ratio Using Korean Multicenter Database
Yunghun You, Yong Chan Shin, Dong Wook Choi, Jin Seok Heo, Sang Hyun Shin, Naru Kim, Kee-Taek Jang, Hongbeom Kim, Chang-Sup Lim, Sun Hee Chang, Kang Min Han, In Woong Han
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A. N. Polyakov, D. V. Podluzhny, Y. I. Patyutko, S. V. Chulkova, A. V. Egorova, I. S. Bazin, M. A. Shorikov, D. Yu. Frantsev, A. Yu. Syskova
Annaly khirurgicheskoy gepatologii = Annals of HPB Surgery.2020; 25(3): 123. CrossRef
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Eleni Gkika, Maria A. Hawkins, Anca-Ligia Grosu, Thomas B. Brunner
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Prognostic Significance of the Lymph Node Ratio in Surgical Patients With Distal Cholangiocarcinoma
Xiaocheng Li, Huapeng Lin, Yu Sun, Jianping Gong, Huyi Feng, Jingkai Tu
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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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Prognostic impact of splenic vessel involvement and tumor size in distal pancreatectomy for adenocarcinoma: a retrospective multicentric cohort study
Dominique Gantois, Théophile Guilbaud, Ugo Scemama, Edouard Girard, Olivier Picaud, Marine Lefevre, Myriam Elgani, Zeinab Hamidou, Vincent Moutardier, Paul Balandraud, Mircea Chirica, Louise Barbier, David Fuks, David Jérémie Birnbaum
Langenbeck's Archives of Surgery.2022; 407(1): 153. CrossRef
Splenic-vasculature involvement is associated with poor prognosis in resected distal pancreatic cancer
Feng Yin, Mohammed Saad, Jingmei Lin, Christopher R Jackson, Bing Ren, Cynthia Lawson, Dipti M Karamchandani, Belen Quereda Bernabeu, Wei Jiang, Teena Dhir, Richard Zheng, Christopher W Schultz, Dongwei Zhang, Courtney L Thomas, Xuchen Zhang, Jinping Lai,
Gastroenterology Report.2021; 9(2): 139. CrossRef
Meta-analysis of recurrence pattern after resection for pancreatic cancer
M Tanaka, A L Mihaljevic, P Probst, M Heckler, U Klaiber, U Heger, M W Büchler, T Hackert
British Journal of Surgery.2019; 106(12): 1590. CrossRef
Improved Survival in Patients with Resected Pancreatic Carcinoma Using Postoperative Intensity-Modulated Radiotherapy and Regional Intra-Arterial Infusion Chemotherapy
Ningyi Ma, Zheng Wang, Jiandong Zhao, Jiang Long, Jin Xu, Zhigang Ren, Guoliang Jiang
Medical Science Monitor.2017; 23: 2315. CrossRef
Role of Adjuvant Radiotherapy in Left-Sided Pancreatic Cancer—Population-Based Analysis with Propensity Score Matching
Yu Jin Lim, Kyubo Kim, Eui Kyu Chie, BoKyong Kim, Sung W. Ha
Journal of Gastrointestinal Surgery.2015; 19(12): 2183. CrossRef

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Effects of Some Korean Food Extracts on In Vitro Benzo(a)pyrean Metabolism by Rat Liver Microsomal Preparation and its DNA Pamaging Effect: Sun Whe Kim, Jin Pok Kim, Sang Chul Park; J Korean Cancer Assoc. 1989;21(1):18-35.

Abstract PDF: N umerous epidemiologic and experimental studies have proven that there is a close cause and effect relationship between diet and cancer. Several Korean traditional foods (ginseng, red pepper, maejoo, onion, natural salt, garlic) were chosen in order to find if there is any effect of those food materials on the chemical carcinogenesis. To evaluate effects of food extracts on the metabolism of chemical carcinogen, metabolite patterns of benzola)pyrene (B(a)p), especially of 3-hydroxy benzo(a)pyrene (3-OH) as major metabolite, 7, 8-dihydrodiol (7,8-diol), precursor of ultimate carcinogen 7,8-diol-9,10-epoxide, praduced by in vitro metabolism by rat liver Sg were analysed and compared with those in the presence of acetone soluble fractions of food materials, using high performance liquid chromatography (HPLC). And to find the biologic significance of these results, DNA damaging effect of B(a)p was measured and compared with that in the presence of food extracts using SOS chromotest. As a result of analysis using HPLC, 7,8-diol production rate was increased in the presence of the extracts of ginseng, onion and natural salt, while decreased in the presence of the extracts of maejoo, red pepper and garlic. 7,8-diol/3-OH ratio was markedly increased in the presence of red pepper and decreased in the presence of onion. In SOS chromotest, ginseng, red pepper and natural salt had enhancing effect in contrast that maejoo, onion and garlic had inhibitory effect of the SOS inducing act.ivity of B(a)p in the presence of S9. Namely, ginseng and natural salt increased both detoxifying and bioactivating metabolism of B(a) p and enhanced the DNA damaging effect, while maejoo and garlic decreased both detoxifying and bioactivating metabolism and DNA damaging effect. And by red pepper, the detoxifying metabolism was markedly decreased and bioactivation was relatively increased as well as DNA damaging effect. While the detoxifying metabolism was markedly increased by onion, bioactivation was relatively decreased as well as DNA damaging effect. Therefore, it is evident that various food extracts could have some effects on the metabolism of chemical carcinogen, specifically on the production of procarcinogen and the DNA damaging effect of chemical carcinogen.

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Establishment of SNU cell lines: november 1989-august 1990: Jae Gahb Park, You Me Jeon, Kyu Ju Park, Han Kwang Yang, Dong Young Noh, Sun Whe Kim, Seung Keun Oh, Kuhn Uk Lee, Yong Hyun Park, Kuk Jin Choe, Jin Pok Kim, Soo Tae Kim; J Korean Cancer Assoc. 1991;23(2):169-187.

Abstract PDF: No abstract available.

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The Effect of Splenectomy on the Prognosis of Gastric Cancer: Seong Chul Kim, Sun Whe Kim, Sung Han Bae, Jae Gahb Park, Jin Pok Kim; J Korean Cancer Assoc. 1989;21(1):74-82.

Abstract PDF: 1n the surgery of gastric cancer, combined splenectomy has been advocated in order to enhance the radical nature of the operation. In some cases, splenectomy is done due to incidental injury of the spleen during the operation. There may be micrometastasis of gastric cancer to the lymph node of the splenic hilum or the splenic artery. When gastrectomy with combined splenectomy be performed for gastric cancer, though it can remove the micrometastasis to ihe lymph node of the splenic hilum or splenic artery, postsplenectomy change will affect the body. In order to examine the effect of splenectomy-incidental or as a part of curative resection-on the postoperative course of the gastric cancer patients, we studied the cases of gastrectomy with splenectomy for stage II and stage III gastric cancer, and compared with those of gastrectomy without splenectomy for the same stage. The results were as follows; from 1970 to 1986, the number of cases of gastrectomy with splenectomy for stage II and stage III gastric cancer was 90, among which retrospective study was possible in 74 cases; stage II 25cases, stage III 49 cases. 1) The cumulative survival rates of gastrectomy with splenectomy group in stage II gastric cancer were 1 year 96.0%, 2 year 84.0%, 3 year 79.8%, 4 year 74.8%, and 5 year 69.0%-100%, 85.7%, 85.7%, 76.1%, 76.1% in radical subtotal gastrectomy with splenectomy group and 90.1%, 81.8%, 72.7%, 72.7 %, 62.3% in total gastrectomy with splenectomy group, respectively. In stage III gsstric cancer, gastrectomy with splenectomy showed that 1, 2, 3, 4 and 5 year survival rates were 89.8%, 46.9%, 23.5%, 17.1%, and 17.1%, respectively -88.0%, 36,0%, 20.0%, 16.09o, and 16. 0% in radical subtotal gastrectorny with splenectomy group and 91.7%, 58.3%, 26.9%, 17.9 %, and 17. 9% in total gastrectomy with splenectomy group. 2) The splenectomy had the negative effect on the stage III gastric cancer (p < 0.001, Log-rank test). The negative effect on the subtotal gastrectomy for stage Ill gastric cancer was statistically significant (p < 0.010) but not on the total gastrectomy for stage III gastric cancer. 3) The portion of lymphocytes to the white blood cells and the number of platelets per cubic millimeter increased postoperatively in the group surviving more than 3 years, which is consistent with the postsplenectomy change, but not in the patients who could not survive 3 years after operation. 4) The postoperative complications developed in 8 cases-pfeural effusion in 4 cases, LUQ abscess in 2 cases, fever, unknown origin in 1 case, and meningitis in 1 case.

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Significance of chromogranin-A expression in the bile duct cancer: Sun Whe Kim, Woo Ho Kim, Sam Je Cho, Yong Hyun Park; J Korean Cancer Assoc. 1993;25(4):501-506.

Abstract PDF: No abstract available.

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The Effect of Adjuvant Therapy for Curatively Resected Extrahepatic Bile Duct Cancer: Won Shik Han, Sang Jae Park, Sun Whe Kim, Ki Hwan Kim, Sung Whan Ha, Yung Jue Bang, Noe Kyeong Kim, Yong Hyun Park; J Korean Cancer Assoc. 1999;31(6):1253-1260.

Abstract PDF: PURPOSE
This study was attempted to evaluate the effect of adjuvant radiotherapy and chemotherapy after curative resection of extrahepatic bile duct cancer.
MATERIALS AND METHODS
The authors performed a retrospective analysis of 57 patients with extrahepatic bile duct cancer not involving the hepatic duct confluence and curatively resected at Seoul National University Hospital between 1990 and 1995. Resection margins of all cases were confirmed pathologically as free of cancer cells. Among 57 patients, 29 received adjuvant therapy. Total 4000 cGy of external beam radiation was delivered to each. 5-fluorouracil (5-FU) was administered as a radiosensitizer. After 4 weeks of radiation therapy, 5-FU maintenance chemotherapy was started and given every 4 weeks up to 12 cycles or until evidence of relapse.
RESULTS
The overall median survival of 57 patients was 24 months. I- and 2-year overall survival rate was 73.7 and 52.6%. There was no difference in overall survival rate between adjuvant therapy group (n=29) and operation-only group (n 28). We tried to evaluate the effect on survival of adjuvant therapy according to lymph node status. Patients of Tl stage were excluded from analysis. Adjuvant therapy had no survival benefit in the lymph node positive group. But in the lymph node negative group, 1- and 2-year survival rate of patients who underwent adjuvant therapy were 89.5% and 68.4% whereas 1 and 2-year survival rate of patients in operation-only group were 57.9% and 36.8%, which was statistically significant (p=0.0278, 0.0472). And by multivariate analysis, the survival improvement of 1- and 2-year survival rate in adjuvant therapy group was due to adjuvant therapy itself.
CONCLUSION
Our trial of external beam radiotherapy combined with 5-FU chemotherapy after curative resection of extrahepatic bile duct cancer did not show improved overall survival. However the 1- and 2-year survival rate of patients with negative lymph node and advanced T stage ( > T 1) were improved in adjuvant therapy group, so adjuvant therapy may give survival benefit to a certain patient group with negative lymph node.

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Effect of intracelluar cyclic AMP on EGF receptor binding in human gastric adenocarcinoma cells: Sun Whe Kim, Jin Pok Kim; J Korean Cancer Assoc. 1993;25(2):166-169.

Abstract PDF: No abstract available.

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Clinical Significance of p53, c-erbB-2, Chromogranin A and PCNA in the Ampullary Carcinoma: Ki Hwan Kim, Sun Whe Kim, Woo Ho Kim, Yong Hyun Park; J Korean Cancer Assoc. 2001;33(1):84-91.

Abstract PDF: PURPOSE
To determine the clinical significance of p53, c-erbB-2, chromogranin A (CgA), proliferating cell nuclear antigen (PCNA) expression in ampullary carcinoma, a retrospective study was performed.
MATERIALS AND METHODS
The cases of 96 patients who underwent curative resection for ampullary carcinoma during the ten-year period (1986-95) were reviewed. And, using paraffin-embedded tumor tissues, immunohistochemical (IHC) staining for p53, c-erbB-2, CgA, and PCNA was performed.
RESULTS
The overall five-year survival rate (5-YSR) for these 96 patients was 58%. With regard to TNM stage, the 5-YSR was 71% for stage I (n=36), 62% for stage II (n=29), and 39% for stage III (n=31), respectively. IHC expression rate was 17.6% for c-erbB-2, 19.2% for CgA, and 42.9% for p53. The relative proportion of labelling index of PCNA (<25%, 25-50%, >50%) was 30.8%, 25.3%, and 44.0%, respectively. The PCNA labelling index showedsignificant correlation with tumor size (p=0.032). The PCNA labelling index, c-erbB-2, CgA and p53 were not correlated to extent of invasion, lymph node metastasis, stage, or histologic type. CgA and c-erbB-2 expression and the PCNA labelling index thus had no prognostic value. With regard to p53, the 5-YSR of p53 negative cases was 68.6%; that of p53 positive cases was 47%, with significant difference (p=0.038).
CONCLUSION
This result suggests that p53 expression is related to poor prognosis of ampullary carcinoma, and that c-erbB-2 and CgA expression, and the PCNA labelling index, are not significant prognostic factors.

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Hereditary Breast Cancer : Report of three families: Hwan Young Yoo, Sun Whe Kim, Jae Gahb Park, Kuk Jin Choe; J Korean Cancer Assoc. 1994;26(4):642-650.

Abstract PDF: Hereditary breast cancer (HBC) is known to comprise about 5% of all breast cancers. HBC is also known to have early age of onset, be usually bilateral, snd have genetic heterogeneity and verticaI transmission by autosomal dominant pattern. Authors experienced three Korean families with hereditary breast cancer, sa hereby report the cases. A 71-year old female patient (proband of family SNU-Bl) visited our clinic with the chief complaint of upper outer quadrant mass in right breast. She had the past medical history of right nephrectomy four years ago due to renal cell carcinoma. On family history patients younger sister died with uterine cancer. Patients daughter had modified radical mastectomy due to breast cancer at the age of 36 years. Other family members had no specific medical history. The second family (SNU-B2) had three breast cancer patients associated with gastrointestinal tract cancer patients; they occurred between sisters. Their father died with advanced gastric cancer at the age of 67 years, and two elder brothers of the sisters had lung cancer and rectal cancer, each. Other family member had no specific medical history. The third family (SNU-B3) involves twenty-five-year old female patient (proband of SNU- B3) who visited our clinic due to the bilateral breast masses. Mammography and subsectuent fine needle aspiration cytology revealed that both breast mass contained malignant cells. Uterine mass and mutiple solid and cystic left ovarian masses were found by pelvic ultrasonography. On family history, Patients mother had had metachronous bilateral breast cancers at the premenopausal age and died of multiple metastases, and patients sister was found ta have breast cancer. She discharged without treatment by her wilL With the progress of molecular biology, genetic meohanisms of HBC will be found. As HBC has different diagnostic and therapeutic implications, and careful history taking can reveal this entity, it may be the surgeonss responsibility to detect HBC.

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Evaluation of the Cell Mediated Cytotoxicity Against SS-1 Cell Line in the Stomach Cancer Patients - A Comparison with the NK cell activity against K-562 cell -: Ik Chang Oh, Sun Whe Kim, Jae Gahb Park, Jin Pok Kim; J Korean Cancer Assoc. 1985;17(1):72-85.

Abstract PDF: The human natural killer cell mediated cytotoxicity against K-562 myeloid cell line and lymphocyte mediated cytotoxicity against SS- I (Seoul National University, Adenocarcinoma of the Stomach- I) cell line were investigated in a 16-hour "Cr release assay hy using, as effectar cells, peripheral blood lymphocytes from 30 healthy donors, 60 stomach cancer patients and 15 colorectal cancer patients with a 40: 1 effector-to-target cell ratio. The lymphocyte mediated cytotoxicity of those effector cells against K-562 and SS-I was compared with each other to find any difference if present, and the value of the SS- I as a target cell in vitro cytotoxicity test was investigated. The NK cell activity of control group against K-562 was 61. 5 +- 10.5%, that of stomach cancer patients was 44.3-11. 6% and that of colorectal cancer patients was 46.4 +- 7.2%. Tbe lymphocyte mediated cytotoxicity of control group against SS- I was 66.8+9.9%, that of stomach cancer patients was 46.4+13.2% and that of colorectal cancer patients was 50.8+-11.7%. There was no difference of NK cell activity against K-562 and of cytotoxicity against SS- I between male and female sex in each target cell group. There was no evidence of carrelation between the degree of NK cell activity of atomach cancer patients and the severity of the cancer as shown with clinical atage, and the T-cell count of the stomach cancer patients. The NK cell activity did not vary with the patient's age in the stomach cancer patients. The cytotoxicity of the lymphocytes from the stomach cancer patients and the colorectal cancer patients against both target cells were significantly lower than those of control group. And there was no significant difference between the cytotoxicity of stomach cancer patients and that of colorectal cancer patients against both traget cells. The spontaneous lymphocyte mediated cytotoxicity against SS-I was significantly higher than that against K-562 in the control group; this means that SS-I has antigen or structure which can be recognized by the human NK cells. With those results, it seems that the SS-I cell line is another target cell which can be used in vitro cytotoxicity test for various cancer patients especially somach and colorectal cancer patients.

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K-ras Mutation in Ampulla of Vater Cancer: Sang Jae Park, Sun Whe Kim, Woo Ho Kim, Jin Young Jang, Yong Hyun Park; J Korean Cancer Assoc. 2000;32(5):981-988.

Abstract PDF: PURPOSE
The aims of this study was to elucidate the role of the K-ras mutation (codon 12) in the carcinogenesis of ampulla of Vater cancer.
MATERIALS AND METHODS
31 cases of radically resected ampullary cancer cases were enrolled. 18 cases harbored the adenomatous portions adjacent to carcinomatous portions. Utilizing a two-step nested PCR with RFLP method, we examined the K-ras mutation in a total of 90 samples (normal mucosas (N=31), carcinomatous portions (N=31), adenomatous portions (N=18), and metastatic lymph nodes (N=10)).
RESULTS
In the carcinomatous portion, K-ras mutations in codon 12 were detected in 48.4%. In the adenomatous portions, 10 cases (55.6%) out of 18 displayed the K-ras mutation. In the metastatic lymph nodes, K-ras mutation was found in 4 cases out of 10. After sequencing, 4 mutant types (GTT, GAT, GCT and TGT) of codon 12 (normally GGT) in the ampulla of Vater cancer were detected and the mutated types in the adenomatous portions, carcinomatous portions and metastatic lymph nodes in the same cases were identical. CONCLUSION: The presence of concomitant K-ras mutation in both the adenomatous and carcinomatous portions in some cases may suggest the role of K-ras mutation in the early carcinogenesis of ampulla of Vater cancer.

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Local Recurrence after Curative Resection for Rectal and Rectosigmoid Carcinoma : Relationship with various factors including extent of distal clearance: Jin Pok Kim, Jae Gahb Park, Sun Whe Kim; J Korean Cancer Assoc. 1985;17(1):85-94.

Abstract PDF: The hospital records of 267 patients who had undergone curative resection for rectal or rectosigmoid cancer at Seoul National University Hospital between 1974 and 1982 were reviewed. Of these, 34 patients were lost to follow-up and the status of recurrence of 51 patients were unknown. The remaining 182 Patients were analysed to ascertain whether there is any correlation between local recurrence rate and various factors including the length of normal rectum removed below the tumor. Fifty one patients(28%) developed local recurrence; 39/115(34%) after abdominoperineal excision and 12/67(18%) after sphincter- saving operation. Clinical stage, location of tumor, histolagic differentiation, number of .etastatic lymph nodes and adhesion to surrounding tissue as an operative finding were 'ound to have an influence on the local recurrence rate. There was no difference in the ocal recurrence rate between two types of operation for Dukes C lesion excluding low rectal :ancers. Of the 67 patients who had undergone sphincter-saving operation, the length of the ectum excised below the tumor was less than 2 cm in 10 patients(group 1), 2 cm or more .nd less than 5 cm in 15 patients(group 2) and 5 cm or more in 42 patients(group 3). The ates of local recurrence of group 1, 2 and 3 were 30i.(3/10), 13. 3%(2/15) and 16. 7%(7/42). But the proportian of the patients who had metastatic lymph nodes, especially multiple ymph node involvement was significantly larger in group 1 than in other groups. All the cases in group 1 developed local recurrence at the anastomosis site. These results suggest hat clinical stage and other risk factors has more important role on increasing rate of local :currence than the length of the rectum excised below tumor, but a margin less than 2 cm elow the tumor increases the risk of suture line recurrence.

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Multiple Primary Colorectal Cancers: Sun Whe Kim, Jae Gahb Park, Jin Pok Kim; J Korean Cancer Assoc. 1985;17(1):94-103.

Abstract PDF: The medical records of 425 patients with colorectal cancer operated at the Seoul National University Hoapital between 1978 and 1983 were examined. Fourteen cases (3.3%) of multiple primary colorectal cancers were identified. Eleven pat,ients (2.6%) were found to have synchronous multiple cancer and 5 patients (l.2%), metachranous cancer. Two of 14 patients (0.5%) were found to have both synchronous and metachronous cancers. A total of 34 tumora was involved; 12 in the rectum, 4 in the hepatic flexure, 3 each in the ascending, transverse, descending and sigmoid colon and rectosigmoid area, 2 in the cecum and one in the appendix. Seven patients (50%) had concomitant adenomatous polyp and 2 of them had family history of colorectal cancer. Seven of 13 patients with available pathology report had regional lymph ncde metastasis and one of them had metastatic nodules on the mesentery. All the patients with synchronous tumors except one were treated by standard partial colectomy for each tumors. Five patients with metachranous tumors were treated in the same way, but two of them had subtotal colectomy for second metachronous cancer.

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Significance of CEA Measurement in Colorectal Carcinoma: Jin Pok Kim, Sun Whe Kim; J Korean Cancer Assoc. 1986;18(2):215-225.

Abstract PDF: Preoperative plasma CEA levels were measured in 502 Patients with colorectal cancer and were examined for clinical significance in disease extent and prognosis. The progress of 261 Patients operated upon for cure of colorectal carcinoma was followed postoperatively with a standardized protocol and significance of plasma CEA level for detection of recurrence, timing of detection and site of recurrence was analysed. The preoperative CEA levels showed normal value(less than 2. 5 ng/ml) in 27. 7% of cases, however, it showed relatively good correlation with disease extent, resectability, histologic differentiation, survival and disease free survival, significant difference of which were noted between lower than 5 ng/ml group and 5 ng/ml or higher group. TVhen the upper limit for CEA of 5 ng/ml was allowed, sensitivity, specificity and pre- dictive value for recurrence were 78.3%, 89.3% and 80% respectively. Median interval between CEA elevation and clinical recurrence was 2.1 months. Site of recurrence-locore- gional or distant-was correlated with CEA level at recurrence.

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Testing of LAK Cell Activity Using a Tetrazolium-based Colorimetric ( MTT ) Assay: Jae Gahb Park, Oh Hoong Kwon, Sun Whe Kim, Jin Pok Kim, Kyung Soo Hahm, Moon H. Han; J Korean Cancer Assoc. 1987;19(2):68-79.

Abstract PDF: Peripheral blood lymphocytes of normal individuals can be activated by culture with recombinant Interleukin-2 (donated by Genetic Engineering Center, KAIST, Seoul, Korea) leading to expression of cytotoxic activity toward on colorectal carcinoma cell line SNU-C5. After 4 days incubation, the LAK cells were removed by 4 times washing and the number of live target cells in the microtest plates were counted by the tetazolium-based colorimetric (MTT) assay and the survival rate of the target cells was calculated against the control in which the target cells were incubated without Interleukin-2 and effector cells. During 5 days culture, the recombinant KAIST Interleukin-2 induced the potent LAK cells at the concentration of 0.1 U/ml. After 4 days incubation, almost all target cells (SNU-C5) were killed by the LAK cells of 5 days culture when the Effector:Target ratio were 10 : 1 and 5 : l. SNU C5 represented high adhesiveness to the culture flask and microtest plate bottom, so it can be used for the tetazolium based colorimetric (MTT) assay. Tetrazolium-based colorimetric (MTT) assay shows good carrelation between spectrophotometric absorbance and cell number, and it is long-term assay over other cytotoxicity test methods, so semiautomated MTT assay offers a valid. rapid, and simple method to assess cytotoxicity of LAK cells.

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Operative Treatment for Recurrent Gastrointestinal Malignancies: Seung Ik Ahn, Sun Whe Kim, Jae Gahb Park, Jin Pok Kim; J Korean Cancer Assoc. 1987;19(2):87-95.

Abstract PDF: Total of 146 patients, operated between January, 1974 and December, 1985 for recurrent or metastatic gastrointestinal malignancies were evaluated. Among them, the recurrent stomach cancers were 91 cases and the recurrent colorectal cancers were 37 cases. Age incidence was most prevalent in the 5th decade of life and male to female ratio was 1.1:l. In reoperated stomach cancers the recurrence was closely related to the clinical stage, histologic differentiation or number of metastatic lymph nodes, but in reoperated colorectal cancers those relations were not found. In 83 (64.8%) of 128 cases recurrences were detected within the first 2 years after primary operation and 59 (46.1%) were the local recurrences only. Clinical status due to the recurrences mainly were the intesinal obstruction and recurrence at anastomotic site. In recurrent colorectal cancers, distant metastasis were related with the higher CEA level and local recurrencies were related with the lower CEA level. In 11 (12.1%) of the recurrent stomach cancers and 10 (27.0%) of recurrent colorectal cancers, curative operations were performed. The postoperative complications were 2 cases and postoperative mortalities were 3 cases. The recurrent colorectal cancers revealed the loger survival time than the recurrent stomach cancers, and the curative resections were followed by the higer survival rates than the palliative operations.

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Carcinoma in Choledochal Cyst: Sun Whe Kim, Seon Hee Kim, Yong Hyun Park; J Korean Cancer Assoc. 1995;27(1):61-69.

Abstract PDF: The incidence of carcinoma in choledochal cyst is much higher than that of normal population. The mechanism of carcinogenesis in choledochal cyst is not clear, though reflux of pancreatic juice and stasis of bile appears to be important factors. To study the clinical characteristics of carcinoma in choledochal cyst and to present the rationale that resection is the choice of surgery in choledochal cyst, we reviewed 8 cases of carcinoma in choledochal cyst. The risk of carcinoma in choledochal cyst was 13.1%(GB cancer; 2 cases, CBD cancer; 5 cases, periampullary cancer; 1 case). The sex ratio(M:F= l: 1) and mean age(41 yrs) were intermediate between choledochal cyst(l:3, 36 yrs) and other bile duct cancer(2:1, 59 yrs). All patients had abdominal pain and 4 cases had weight loss which was rare in patients with choledochal cyst only. Five cases were type I and 3 cases were type IVa by Todani type. Anomalous pancreaticobiliary ductal union could be confirmed in 3 cases. Radical operations were possible in one case of GB cancer who received cholecystectomy and cyst excision, and in 2 cases of common bile duct cancer who received Whipples operation. Four patients who had previous history of biliary operation 1 month to 4 years before, received only palliative operation. The patient with periampullary cancer discharged without operation due to multiple liver metastasis. All patients expired between 3 months to 13 months after diagnosis of cancer except 2 patients: one patient who underwent cholecystectomy and cyst excision due to early GB cancer, has been alive for 5 years and one patient who underwent pailliative cystojejunostomy has been alive with disease for 3 months. In conclusion, the risk of carcinoma in choledochal cyst is very high and the prognosis is very poor, so the possibility of cancer association should always be considered and eariy excisional therapy is recommended for those who are diagnosed as choledochal cyst.

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Effects of Dietary Polyunsaturated Fat and Vitamin E on the 1 , 2 - Dimethylhydrazine - induced Colorectal Tumorigenesis in Rats: Young Jin Song, Sun Whe Kim, Jin Pok Kim, Yong Il Kim; J Korean Cancer Assoc. 1988;20(1):8-24.

Abstract PDF: Epidemiologic studies have implicated high-fat diet as a major contributing factor in the develop- ment of human colorectal cancer. Animal model studies have also provided the evidence for the promoting effect of high-fat diet on the 1,2-dimethylhydrazine(DMH)-or azoxymethane(AOM)- induced colorectal tumorigenesis. But there are no reported epidemiologic studies correlation vitamin E consumption with colorectal cancer incidence rates worldwide. In animal model, the effect of vitamin E enriched diet on DMH-or AOM-induced colorectal tumorigenesis still remains controver- sial. The purpose of the present experiment is to elucidate the effect of moderate-fat diet and vitamin E enriched diet on colorectal tumorigenesis in female Wistar rats. The experimental diets, based on regular rat chow obtained from Sam-Yang Oil & Feed Co. Ltd. were as follows: 1) regular diet, 2) 5 % soybean oil added diet, 3) 5% soybean oil and vitamin E (4001U/kg diet) added diet, 4) vitamin E (400 IU/kg diet) added diet. Animals were fed the experimental diet for a 3-week acclimatization period. Each dietary group was divided into two subgroups and all animals received a 5-week course of weekly subcutaneous injection of either DMH (40 mg/kg body weight) or saline-EDTA solution. Animals were fed the experimental diet until the termination of the experiment. Animals were sacrificed 25 weeks after the first injection. All of 73 saline-EDTA treated rats developed no colorectal tumor. Soybean oil added diet group and vitamin E added diet group showed slightly higher incidence (% of animals with tumors) and multiplicity (tumors/animal) of colorectal tumors than the regular diet group did, but soybean oil and vitamin E added diet group showed significantly higher incidence and multiplicity of colorectal tumors than regular diet group did (p<0.025). Tumors were larger (p>0.1), and carcinomas were numerous (p<0.01) in the groups receiving excess vitamin E supplement to their diet. The above results suggest the synergistic interaction between 5% polyunsaturated fat and excess vitamin E in diet on DMH-induced colorectal tumorigenesis in female Wistar rats

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Natural Killer Cell Activity of Peripheral Lymphocytes from Postoperative Longterm Survivor Patients in Stomach Cancer: Song Kim, Sun Whe Kim, Jin Pok Kim; J Korean Cancer Assoc. 1988;20(1):35-43.

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