Cancer Research and Treatment

Original Articles

Gastrointestinal cancer

Prevalence and Risk Factors of Germline Pathogenic Variants in Pancreatic Ductal Adenocarcinoma: Kum Hei Ryu, Sunhwa Park, Jung Won Chun, Eunhae Cho, Jongmun Choi, Dong-Eun Lee, Hyoeun Shim, Yun-Hee Kim, Sung-Sik Han, Sang-Jae Park, Sang Myung Woo, Sun-Young Kong; Cancer Res Treat. 2023;55(4):1303-1312. Published online April 3, 2023; DOI: https://doi.org/10.4143/crt.2023.291

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Purpose
The genetic attribution for pancreatic ductal adenocarcinoma (PDAC) has been reported as 5%-10%. However, the incidence of germline pathogenic variants (PVs) in Korean PDAC patients has not been thoroughly investigated. Therefore, we studied to identify the risk factors and prevalence of PV for future treatment strategies in PDAC.
Materials and Methods
Total of 300 (155 male) patients with a median age of 65 years (range, 33 to 90 years) were enrolled in National Cancer Center in Korea. Cancer predisposition genes, clinicopathologic characteristics, and family history of cancer were analyzed.
Results
PVs were detected in 20 patients (6.7%, median age 65) in ATM (n=7, 31.8%), BRCA1 (n=3, 13.6%), BRCA2 (n=3), and RAD51D (n=3). Each one patient showed TP53, PALB2, PMS2, RAD50, MSH3, and SPINK1 PV. Among them, two likely PVs were in ATM and RAD51D, respectively. Family history of various types of cancer including pancreatic cancer (n=4) were found in 12 patients. Three patients with ATM PVs and a patient with three germline PVs (BRCA2, MSH3, and RAD51D) had first-degree relatives with pancreatic cancer. Familial pancreatic cancer history and PVs detection had a significant association (4/20, 20% vs. 16/264, 5.7%; p=0.035).
Conclusion
Our study demonstrated that germline PVs in ATM, BRCA1, BRCA2, and RAD51D are most frequent in Korean PDAC patients and it is comparable to those of different ethnic groups. Although this study did not show guidelines for germline predisposition gene testing in patients with PDAC in Korea, it would be emphasized the need for germline testing for all PDAC patients.

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FOXM1 promotes malignant biological behavior and metabolic reprogramming by targeting SPINK1 in hepatocellular carcinoma and affecting the p53 pathway
Xu Ding, Jinjun Shi, Zhengqing Lei, Guoqing Wang, Chenchun Fu, Xiangyu Su, Guangyu Zhu
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease.2025; 1871(3): 167673. CrossRef
MLH1 Inhibits Metastatic Potential of Pancreatic Ductal Adenocarcinoma via Downregulation of GPRC5C
Wen-Jing Liu, Jun Lu, Wei-Xun Zhou, Jian-Zhou Liu, Li Zhou
Laboratory Investigation.2024; 104(9): 102107. CrossRef
Clinical Significance of PALB2 Pathogenic Germline Variant
Min-Chae Kang, R.N., Jong Eun Park, Mi-Ae Jang, Dongju Won, Boyoung Park, Seeyoun Lee, Dong Ock Lee, Kum Hei Ryu, Yoon-Jung Chang, Sun-Young Kong
Laboratory Medicine Online.2024; 14(4): 311. CrossRef
Prevalence Estimation of the PALB2 Germline Variant in East Asians and Koreans through Population Database Analysis
Jong Eun Park, Min-Chae Kang, Taeheon Lee, Eun Hye Cho, Mi-Ae Jang, Dongju Won, Boyoung Park, Chang-Seok Ki, Sun-Young Kong
Cancers.2024; 16(19): 3318. CrossRef
Understanding the Genetic Landscape of Pancreatic Ductal Adenocarcinoma to Support Personalized Medicine: A Systematic Review
Antonino Pantaleo, Giovanna Forte, Candida Fasano, Martina Lepore Signorile, Paola Sanese, Katia De Marco, Elisabetta Di Nicola, Marialaura Latrofa, Valentina Grossi, Vittoria Disciglio, Cristiano Simone
Cancers.2023; 16(1): 56. CrossRef

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Prevalence of Psychological Symptoms in Patients Undergoing Pancreatoduodenectomy and Results of a Distress Management System: A Clinic-Based Study: Mee Joo Kang, Eun-Seung Yu, Young Hwa Kang, Hyeong Min Park, Sang-Jae Park, Sun-Whe Kim, Jong-Heun Kim, Sung-Sik Han; Cancer Res Treat. 2022;54(4):1138-1147. Published online January 4, 2022; DOI: https://doi.org/10.4143/crt.2021.842

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Purpose
Patients undergoing pancreatoduodenectomy are a high-risk group that requires psychosocial support. This study retrospectively reviewed the prevalence of psychological symptoms in patients undergoing pancreatoduodenectomy for periampullary neoplasm and the psychosocial referral rate after implementing full screening and triage algorithm for administering a distress management protocol based on the integrated supportive care system established in 2010.
Materials and Methods
From September 2010 to December 2018, insomnia, anxiety, and depression were screened on the first day of admission (T1) and on the 10th postoperative day (T2). Patients with clinical levels of distress were referred to a mental health clinic for appropriate aftercare.
Results
The adherence rate to routine screening was 82.7% (364/440). Among the 364 patients, the prevalence of insomnia, anxiety, and depression increased from 22.0% (T1) to 32.6% (T2, p=0.001), 29.1% to 33.6% (p=0.256), and 18.4% to 27.6% (p=0.001), respectively. Less than 45% of those with psychological symptoms expressed their needs for psychological supportive care. Among those with psychological symptoms at T2, clinical insomnia, anxiety, and depression were detected via in-depth evaluations among 77.2%, 38.1%, and 82.5% of patients, respectively. Patients who had two or more symptoms at T2 had a longer postoperative hospital stay, as compared to those with one or no symptoms (a median of 20.5 days vs. 18.0 days, p=0.006). Psychiatric consultation rate was 72.8% among patients with clinical psychological symptoms, and 74% of the consulted patients completed psychiatric intervention before discharge.
Conclusion
Over one-third of the patients had psychological symptoms before and after pancreatoduodenectomy. Implementing a routine psychological symptoms screening with a systematic psychiatric referral protocol enhanced surgeons’ responsiveness to patients’ psychological symptoms.

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Assessing the long-term priorities of pancreaticoduodenectomy survivors
Edward A. Joseph, Kara D. Bowers, Rebecca Marcus, Bibek Aryal, Suzanne C. Schiffman, Patrick L. Wagner, Sricharan Chalikonda, David L. Bartlett, Casey J. Allen
HPB.2024; 26(5): 703. CrossRef
Effect of postoperative application of esketamine on postoperative depression and postoperative analgesia in patients undergoing pancreatoduodenectomy: a randomized controlled trial protocol
Kaili Yu, Zhenguo Song, Bowen Zhang, Qian Pan, Shan Gan, Shaoyong Yang, Quanyong Yang, Xinhua Zuo, Yiqing Yin
Trials.2023;[Epub] CrossRef

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First Course of treatment and Prognosis of Exocrine Pancreatic Cancer in Korea from 2006 to 2017: Mee Joo Kang, Jiwon Lim, Sung-Sik Han, Hyeong Min Park, Sang-Jae Park, Young-Joo Won, Sun-Whe Kim; Cancer Res Treat. 2022;54(1):208-217. Published online May 21, 2021; DOI: https://doi.org/10.4143/crt.2021.421

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Purpose
Hospital-based clinical studies have limitations in holistic assessment of cancer treatment and prognosis, as they omit out-of-hospital patients including elderly individuals. This study aimed to investigate trends in initial treatment and corresponding prognosis of patients with exocrine pancreatic cancer (EPC) in Korea.
Materials and Methods
The Korea Central Cancer Registry data of patients with EPC from 2006 to 2017 were retrospectively reviewed. We defined the first course of treatment (FT) as the cancer-directed treatment administered within four months after cancer diagnosis according to Surveillance, Epidemiology, and End Results (SEER) program.
Results
Among 62,209 patients with EPC, localized and regional (LR) SEER stage; patients over 70 years old; and ductal adenocarcinoma excluding cystic or mucinous (DAC) accounted for 40.6%, 50.1%, and 95.9%, respectively. “No active treatment” (NT, 46.5%) was the most frequent, followed by non-surgical FT (28.7%) and surgical FT (22.0%). Among 25,198 patients with LR EPC, surgical FT increased (35.9% to 46.3%) and NT decreased (45.0% to 29.5%) from 2006 to 2017. The rate of surgical FT was inversely related to age (55.1% [< 70 years], 37.3% [70-79 years], 10.9% [≥ 80 years]). Five-year relative survival rates of LR DAC were higher after surgical FT than after NT in localized (46.1% vs. 12.9%) and regional stage (23.6% vs. 4.9%) from 2012 to 2017.
Conclusion
Less than half of overall patients with LR EPC underwent surgical FT, and this proportion decreased significantly in elderly individuals. Clinicians should focus attention on elderly patients with EPC to provide appropriate medical advice.

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Conditional Relative Survival of Exocrine Pancreatic Cancer: A Population-Based Study
Mee Joo Kang, Johyun Ha, Hyeong Min Park, Sang-Jae Park, Kyu-Won Jung, Sung-Sik Han
Annals of Surgical Oncology.2024; 31(2): 1178. CrossRef
Potential role of Fibrosis‐4 score in hepatocellular carcinoma screening: The Kangbuk Samsung Health Study
Sujeong Shin, Won Sohn, Yoosoo Chang, Yoosun Cho, Min‐Jung Kwon, Sarah H. Wild, Christopher D. Byrne, Seungho Ryu
Hepatology Research.2024; 54(6): 551. CrossRef
Three-year follow-up study reveals improved survival rate in NSCLC patients underwent guideline-concordant diagnosis and treatment
Huijuan Mu, Xing Yang, Yanxia Li, Bingzheng Zhou, Li Liu, Minmin Zhang, Qihao Wang, Qian Chen, Lingjun Yan, Wei Sun, Guowei Pan
Frontiers in Oncology.2024;[Epub] CrossRef
Epidemiological trends and factors associated with survival in patients with medulloblastoma: A 45-year population-based retrospective study
Dongjie He, Yahui Yang, Peiwen Wu, Siying Zhu, Hao Chang, Chao Zhang, Qiuju Shao, Zongyan Yu
Journal of Clinical Neuroscience.2024; 126: 154. CrossRef
Surgical management for elderly patients with pancreatic cancer
Sun-Whe Kim
Annals of Surgical Treatment and Research.2023; 105(2): 63. CrossRef
Exocrine pancreatic cancer as a second primary malignancy: A population-based study
Mee Joo Kang, Jiwon Lim, Sung-Sik Han, Hyeong Min Park, Sung Chun Cho, Sang-Jae Park, Sun-Whe Kim, Young-Joo Won
Annals of Hepato-Biliary-Pancreatic Surgery.2023; 27(4): 415. CrossRef
Distinct prognosis of biliary tract cancer according to tumor location, stage, and treatment: a population-based study
Mee Joo Kang, Jiwon Lim, Sung-Sik Han, Hyeong Min Park, Sun-Whe Kim, Woo Jin Lee, Sang Myung Woo, Tae Hyun Kim, Young-Joo Won, Sang-Jae Park
Scientific Reports.2022;[Epub] CrossRef
Trend Analysis and Prediction of Hepatobiliary Pancreatic Cancer Incidence and Mortality in Korea
Hyeong Min Park, Young-Joo Won, Mee Joo Kang, Sang-Jae Park, Sun-Whe Kim, Kyu-Won Jung, Sung-Sik Han
Journal of Korean Medical Science.2022;[Epub] CrossRef
Epidemiology of Gastric Cancer in Korea: Trends in Incidence and Survival Based on Korea Central Cancer Registry Data (1999–2019)
Sin Hye Park, Mee Joo Kang, E Hwa Yun, Kyu-Won Jung
Journal of Gastric Cancer.2022; 22(3): 160. CrossRef
Incidence, mortality and survival of gallbladder, extrahepatic bile duct, and pancreatic cancer using Korea central cancer registry database: 1999-2019
Mee Joo Kang, E Hwa Yun, Kyu-Won Jung, Sang-Jae Park
Annals of Hepato-Biliary-Pancreatic Surgery.2022; 26(3): 220. CrossRef
Incidence, mortality, and survival of liver cancer using Korea central cancer registry database: 1999-2019
Sung Yeon Hong, Mee Joo Kang, Taegyu Kim, Kyu-Won Jung, Bong-Wan Kim
Annals of Hepato-Biliary-Pancreatic Surgery.2022; 26(3): 211. CrossRef

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Proximal Resection Margins: More Prognostic than Distal Resection Margins in Patients Undergoing Hilar Cholangiocarcinoma Resection: Tae Yoo, Sang-Jae Park, Sung-Sik Han, Seong Hoon Kim, Seung Duk Lee, Tae Hyun Kim, Soon-ae Lee, Sang Myung Woo, Woo Jin Lee, Eun Kyung Hong; Cancer Res Treat. 2018;50(4):1106-1113. Published online November 16, 2017; DOI: https://doi.org/10.4143/crt.2017.320

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Purpose
Even though the therapeutic gold standard of hilar cholangiocarcinoma (HCCA) resection is cancer-free resection margin (RM), surgical treatment still remains challenging. This study evaluated the prognostic significance of RM status in resected HCCA patients and identified survival prognostic factors.
Materials and Methods
We reviewed records of 96 HCCA patients who underwent surgery from 2001 to 2012 and analyzed the RM status and prognostic factors that affecting survival.
Results
Negative RM (n=31, 33%) was significantly associated with better survival vs. positive RM (n=65, 67%) (mean survival time [MST], 33 months vs. 21 months; p=0.011). Margins with histological findings of non-dysplastic epithelium, low-grade dysplasia, and carcinoma in situ were not associated with survival differences (MST, 33 months vs. 33 months vs. 30 months; p=0.452), whereas positive margins were associated with poorer survival relative to carcinoma in situ (MST, 30 months vs. 21 months; p=0.050). Among patients with R0 resection, narrow (≤ 5 mm) and wide (> 5 mm) margins were not associated with survival differences (MST, 33 months vs. 30 months; p=0.234). Although positive proximal RM was associated with poorer survival compared to negative RM (MST, 19 vs. 33; p=0.002), no survival difference was observed between positive and negative distal RMs (MST, 30 vs. 33; p=0.628). Proximal RM positivity (hazard ratio [HR], 2.688; p=0.007) and nodal involvement (HR, 3.293; p < 0.001) were independent survival prognostic factors.
Conclusion
A clear RM, especially proximal RM status, was significant prognosticator, and proximal bile duct resection to the greatest technically feasible extent may be necessary, with careful consideration of the potential morbidity and oncologic outcomes after resection. However, an aggressive approach to obtain a negative distal RM might be controversial and should be considered carefully, depending on the patient's status.

Citations

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Molecular profiling and prognostic analysis in Chinese cholangiocarcinoma: an observational, retrospective single-center study
Changkun Zhang, Xia You, Qin Zhang, Dong Wang
Investigational New Drugs.2024; 42(1): 24. CrossRef
Radiographic features predictive of recurrence and survival after surgical resection of perihilar cholangiocarcinoma
Julaluck Promsorn, Panjaporn Naknan, Aumkhae Sookprasert, Kosin Wirasorn, Jarin Chindaprasirt, Attapol Titapun, Piyapharom Intarawichian, Mukesh Harisinghani
Heliyon.2024; 10(7): e28805. CrossRef
Practice guidelines for managing extrahepatic biliary tract cancers
Hyung Sun Kim, Mee Joo Kang, Jingu Kang, Kyubo Kim, Bohyun Kim, Seong-Hun Kim, Soo Jin Kim, Yong-Il Kim, Joo Young Kim, Jin Sil Kim, Haeryoung Kim, Hyo Jung Kim, Ji Hae Nahm, Won Suk Park, Eunkyu Park, Joo Kyung Park, Jin Myung Park, Byeong Jun Song, Yong
Annals of Hepato-Biliary-Pancreatic Surgery.2024; 28(2): 161. CrossRef
Influence of Perineural (Pn), Lymphangio (L) and Vascular (V) Invasion on Survival after Resection of Perihilar Cholangiocarcinoma
Rabea Margies, Lisa-Katharina Gröger, Beate K. Straub, Fabian Bartsch, Hauke Lang
Cancers.2024; 16(20): 3463. CrossRef
Liver transplantation for unresectable Klatskin tumor: experience of two centers, first distant results
D. A. Granov, V. N. Zhuikov, I. I. Tileubergenov, A. V. Moiseenko, I. O. Rutkin, A. R. Sheraliev, A. A. Polikarpov, O. O. Rummo, A. E. Shcherba, I. P. Shturich, S. V. Korotkov, L. V. Kirkovsky, T. M. Chernishov
Annaly khirurgicheskoy gepatologii = Annals of HPB Surgery.2024; 29(3): 70. CrossRef
Significance of dysplasia in bile duct resection margin in patients with extrahepatic cholangiocarcinoma: A retrospective analysis
Jung Wan Choe, Hyo Jung Kim, Jae Seon Kim
World Journal of Clinical Cases.2022; 10(10): 3078. CrossRef
Klatskin Tumor: A Survival Analysis According to Tumor Characteristics and Inflammatory Ratios
Vlad-Ionuţ Nechita, Emil Moiş, Luminiţa Furcea, Mihaela-Ancuţa Nechita, Florin Graur
Medicina.2022; 58(12): 1788. CrossRef
Impact of Remnant Carcinoma in Situ at the Ductal Stump on Long‐Term Outcomes in Patients with Distal Cholangiocarcinoma
Koya Yasukawa, Akira Shimizu, Hiroaki Motoyama, Koji Kubota, Tsuyoshi Notake, Kentaro Fukushima, Tomohiko Ikehara, Hikaru Hayashi, Akira Kobayashi, Yuji Soejima
World Journal of Surgery.2021; 45(1): 291. CrossRef
Comprehensive analysis of genomic alterations of Chinese hilar cholangiocarcinoma patients
Feiling Feng, Xiaobing Wu, Xiaoliang Shi, Qingxiang Gao, Yue Wu, Yong Yu, Qingbao Cheng, Bin Li, Bin Yi, Chen Liu, Qing Hao, Lin Zhang, Chunfang Gao, Xiaoqing Jiang
International Journal of Clinical Oncology.2021; 26(4): 717. CrossRef
Prognostic Impact of Perioperative CA19-9 Levels in Patients with Resected Perihilar Cholangiocarcinoma
Jong Woo Lee, Jae Hoon Lee, Yejong Park, Jaewoo Kwon, Woohyung Lee, Ki Byung Song, Dae Wook Hwang, Song Cheol Kim
Journal of Clinical Medicine.2021; 10(7): 1345. CrossRef
Prognostic Predictability of American Joint Committee on Cancer 8th Staging System for Perihilar Cholangiocarcinoma: Limited Improvement Compared with the 7th Staging System
Jong Woo Lee, Jae Hoon Lee, Yejong Park, Woohyung Lee, Jaewoo Kwon, Ki Byung Song, Dae Wook Hwang, Song Cheol Kim
Cancer Research and Treatment.2020; 52(3): 886. CrossRef
Comparative study of laparoscopic‐assisted and open total gastrectomy for Siewert Types II and III adenocarcinoma of the esophagogastric junction
Jianchu Wang, Jin‐Cheng Wang, Bin Song, Xu‐Dong Dai, Xiao‐Yu Zhang
Journal of Cellular Physiology.2019; 234(7): 11235. CrossRef
Surgical management of carcinoma in situ at ductal resection margins in patients with extrahepatic cholangiocarcinoma
Toshifumi Wakai, Jun Sakata, Tomohiro Katada, Yuki Hirose, Daiki Soma, Pankaj Prasoon, Kohei Miura, Takashi Kobayashi
Annals of Gastroenterological Surgery.2018; 2(5): 359. CrossRef

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Induction Chemotherapy with Gemcitabine and Cisplatin Followed by Simultaneous Integrated Boost–Intensity Modulated Radiotherapy with Concurrent Gemcitabine for Locally Advanced Unresectable Pancreatic Cancer: Results from a Feasibility Study: Sang Myung Woo, Min Kyeong Kim, Jungnam Joo, Kyong-Ah Yoon, Boram Park, Sang-Jae Park, Sung-Sik Han, Ju Hee Lee, Eun Kyung Hong, Yun-Hee Kim, Hae Moon, Sun-Young Kong, Tae Hyun Kim, Woo Jin Lee; Cancer Res Treat. 2017;49(4):1022-1032. Published online January 19, 2017; DOI: https://doi.org/10.4143/crt.2016.495

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Purpose
This study assessed the feasibility and compliance of induction chemotherapy with gemcitabine and cisplatin followed by simultaneous integrated boost–intensity modulated radiotherapy (SIB-IMRT) with concurrent gemcitabine in patients with locally advanced unresectable pancreatic cancer.
Materials and Methods
In this trial, patients received induction chemotherapy consisting of gemcitabine (1,000 mg/m²) and cisplatin (25 mg/m2) on days 1, 8, and 15 of each treatment cycle. Patients were subsequently treated with gemcitabine (300 mg/m²/wk) during SIB-IMRT. The patients received total doses of 55 and 44 Gy in 22 fractions to planning target volume 1 and 2, respectively. As an ancillary study, digital polymerase chain reaction was performed to screen for the seven most common mutations in codons 12 and 13 of the KRAS oncogene of circulating cell free DNA (cfDNA).
Results
Forty-four patients were enrolled between 2012 and 2015. Of these, 33 (75%) completed the treatment. The most common toxicities during induction chemotherapy were grades 3 and 4 neutropenia (18.2%), grade 3 nausea (6.8%) and vomiting (6.8%). The most common toxicities during SIB-IMRT were grade 3 neutropenia (24.2%) and grade 3 anemia (12.1%). Ten patients (23%) underwent a curative resection after therapy. Median overall survival was significantly longer in patients who underwent curative resection (16.8 months vs. 11 months, p < 0.01). The median cfDNA concentration was significantly lower after treatment (108.5 ng/mL vs. 18.4 ng/mL, p < 0.001).
Conclusion
Induction chemotherapy with gemcitabine and cisplatin followed by concurrent SIB-IMRT was well tolerated and active.

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Kinetics of plasma cell-free DNA as a prospective biomarker to predict the prognosis and radiotherapy effect of esophageal cancer
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Circulating tumor DNA: a help to guide therapeutic strategy in patients with borderline and locally advanced pancreatic adenocarcinoma?
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Circulating Tumor DNA Detection by Digital-Droplet PCR in Pancreatic Ductal Adenocarcinoma: A Systematic Review
Marisol Huerta, Susana Roselló, Luis Sabater, Ana Ferrer, Noelia Tarazona, Desamparados Roda, Valentina Gambardella, Clara Alfaro-Cervelló, Marina Garcés-Albir, Andrés Cervantes, Maider Ibarrola-Villava
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Irina Palacín-Aliana, Noemí García-Romero, Adrià Asensi-Puig, Josefa Carrión-Navarro, Víctor González-Rumayor, Ángel Ayuso-Sacido
Biomedicines.2021; 9(8): 906. CrossRef
A review on the efficacy and safety of iodine-125 seed implantation in unresectable pancreatic cancers
Sheng-Nan Jia, Fu-Xing Wen, Ting-Ting Gong, Xin Li, Hui-Jie Wang, Ya-Min Sun, Ze-Cheng Yang
International Journal of Radiation Biology.2020; 96(3): 383. CrossRef
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Yonsei Medical Journal.2018; 59(4): 470. CrossRef
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