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Zhou L, Li Y, Ni Y, Liu C. Analysis of postoperative pulmonary complications after gastrectomy for gastric cancer: development and validation of a nomogram. Front Surg 2023; 10:1308591. [PMID: 38186389 PMCID: PMC10768169 DOI: 10.3389/fsurg.2023.1308591] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Accepted: 11/27/2023] [Indexed: 01/09/2024] Open
Abstract
Background Postoperative pulmonary complications (PPCs) are common in gastric cancer patients after gastrectomy. The aim of our study was to investigate the perioperative risk factors and to develop a nomogram to identify patients who are at significant risk of PPCs. Methods The clinical data of gastric cancer patients who underwent elective gastrectomy in the First Affiliated Hospital of Nanjing Medical University from 2017 to 2021 were retrospectively collected. All patients were randomly divided into a training and a validation cohort at a ratio of 7:3. Univariate and multivariate analysis were applied to identify the independent risk factors that might predict PPCs, and a nomogram was constructed. Both discrimination and calibration abilities were estimated by the area under a receiver operating characteristic curve (AUC) and calibration curves. The clinical effectiveness of the nomogram was further quantified with the decision curve analysis (DCA). Results Of 2,124 included patients, one hundred and fifty patients (7.1%) developed PPCs. Binary logistic analysis showed that age > 65 years, higher total cholesterol level, longer duration of surgery, total gastrectomy, and the dose of oxycodone > 5.5 mg were independent risk factors for the occurrence of PPCs, which were contained in the nomogram. The predictive nomogram showed good discrimination and calibration [an AUC of 0.735 (95% CI: 0.687-0.783) in a training cohort and 0.781 (95% CI: 0.715-0.847) in a validation cohort]. The calibration curve and decision curve analysis showed a good agreement between nomogram predictions and actual observations. Conclusion We developed a nomogram model based on age, total cholesterol, extent of resection, duration of surgery, and the dose of oxycodone to predict the risk of PPCs in gastric cancer patients after elective gastrectomy.
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Affiliation(s)
| | | | | | - Cunming Liu
- Department of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
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Park M, Suh JK, Lee JA, Park HJ, Park EY, Yoo CW, Lim MC, Park SY, Park BK. Excellent Outcomes in Children, Adolescents, and Young Adults with Ovarian Germ Cell Tumors Treated by Either Reduced- or Standard-Dose Bleomycin. Cancers (Basel) 2023; 15:5290. [PMID: 37958463 PMCID: PMC10647703 DOI: 10.3390/cancers15215290] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2023] [Revised: 10/20/2023] [Accepted: 10/30/2023] [Indexed: 11/15/2023] Open
Abstract
To investigate the outcomes of children, adolescents, and young adults (AYAs) with malignant ovarian germ cell tumors (MOGCTs), we analyzed the data of 61 patients aged ≤39 years diagnosed with MOGCT between 2006 and 2022. Among 59 patients who received chemotherapy after initial diagnosis, 57 received BEP (standard dose of bleomycin with 30 units per week, n = 13) or bEP (reduced dose of bleomycin with 15 units/m2 on day 1, n = 44). The 5-year overall survival (OS) and event-free survival (EFS) rates were 98.3% and 84.9%, respectively. Reduced bleomycin dose did not adversely affect survival. Normalization of tumor markers within 3 months after surgery was significantly associated with better EFS (p < 0.01). Of the 59 surviving patients, 8 experienced surgery-related menopause, while 49 demonstrated menstrual recovery. After completion of chemotherapy, there was no significant difference in pulmonary function regarding bleomycin dose, and no overt nephrotoxicity. Approximately 60% and 25% of survivors experienced peripheral neuropathy at the end of chemotherapy and after 1 year, respectively (p < 0.01). Children and AYAs with MOGCT have favorable survival rates with minimal long-term toxicity, which are not influenced by a reduced bleomycin dose. Rapid normalization of tumor markers is associated with improved outcomes.
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Affiliation(s)
- Meerim Park
- Department of Pediatrics, Center for Pediatric Cancer, National Cancer Center, Goyang 10408, Republic of Korea; (M.P.); (J.K.S.); (J.A.L.); (H.J.P.)
| | - Jin Kyung Suh
- Department of Pediatrics, Center for Pediatric Cancer, National Cancer Center, Goyang 10408, Republic of Korea; (M.P.); (J.K.S.); (J.A.L.); (H.J.P.)
| | - Jun Ah Lee
- Department of Pediatrics, Center for Pediatric Cancer, National Cancer Center, Goyang 10408, Republic of Korea; (M.P.); (J.K.S.); (J.A.L.); (H.J.P.)
| | - Hyeon Jin Park
- Department of Pediatrics, Center for Pediatric Cancer, National Cancer Center, Goyang 10408, Republic of Korea; (M.P.); (J.K.S.); (J.A.L.); (H.J.P.)
| | - Eun Young Park
- Biostatistics Collaboration Team, Research Core Center, National Cancer Center, Goyang 10408, Republic of Korea;
| | - Chong Woo Yoo
- Department of Pathology, Center for Gynecologic Cancer, National Cancer Center, Goyang 10408, Republic of Korea;
| | - Myong Cheol Lim
- Gynecologic Cancer Branch, Center for Gynecologic Cancer, National Cancer Center, Goyang 10408, Republic of Korea; (M.C.L.); (S.-Y.P.)
| | - Sang-Yoon Park
- Gynecologic Cancer Branch, Center for Gynecologic Cancer, National Cancer Center, Goyang 10408, Republic of Korea; (M.C.L.); (S.-Y.P.)
| | - Byung Kiu Park
- Department of Pediatrics, Seoul Metropolitan Seonam Hospital, Seoul 08049, Republic of Korea
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Yang WJ, Zhao HP, Yu Y, Wang JH, Guo L, Liu JY, Pu J, Lv J. Updates on global epidemiology, risk and prognostic factors of gastric cancer. World J Gastroenterol 2023; 29:2452-2468. [PMID: 37179585 PMCID: PMC10167900 DOI: 10.3748/wjg.v29.i16.2452] [Citation(s) in RCA: 143] [Impact Index Per Article: 71.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2022] [Revised: 03/19/2023] [Accepted: 04/07/2023] [Indexed: 04/24/2023] Open
Abstract
Gastric cancer (GC) is defined as the primary epithelial malignancy derived from the stomach, and it is a complicated and heterogeneous disease with multiple risk factors. Despite its overall declining trend of incidence and mortality in various countries over the past few decades, GC remains the fifth most common malignancy and the fourth leading cause of cancer-related death globally. Although the global burden of GC has shown a significant downward trend, it remains severe in certain areas, such as Asia. GC ranks third in incidence and mortality among all cancer types in China, and it accounts for nearly 44.0% and 48.6% of new GC cases and GC-related deaths in the world, respectively. The regional differences in GC incidence and mortality are obvious, and annual new cases and deaths are increasing rapidly in some developing regions. Therefore, early preventive and screening strategies for GC are urgently needed. The clinical efficacies of conventional treatments for GC are limited, and the developing understanding of GC pathogenesis has increased the demand for new therapeutic regimens, including immune checkpoint inhibitors, cell immunotherapy and cancer vaccines. The present review describes the epidemiology of GC worldwide, especially in China, summarizes its risk and prognostic factors, and focuses on novel immunotherapies to develop therapeutic strategies for the management of GC patients.
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Affiliation(s)
- Wen-Juan Yang
- Department of Clinical Laboratory, Honghui Hospital, Xi'an Jiaotong University, Xi'an 710054, Shaanxi Province, China
| | - He-Ping Zhao
- Department of Clinical Laboratory, Honghui Hospital, Xi'an Jiaotong University, Xi'an 710054, Shaanxi Province, China
| | - Yan Yu
- Department of Clinical Laboratory, Honghui Hospital, Xi'an Jiaotong University, Xi'an 710054, Shaanxi Province, China
| | - Ji-Han Wang
- Institute of Medical Research, Northwestern Polytechnical University, Xi'an 710072, Shaanxi Province, China
| | - Lei Guo
- Department of Spinal Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an 710054, Shaanxi Province, China
| | - Jun-Ye Liu
- Department of Clinical Laboratory, Honghui Hospital, Xi'an Jiaotong University, Xi'an 710054, Shaanxi Province, China
| | - Jie Pu
- Department of Cardiology, Shaanxi Provincial People’s Hospital, Xi'an 710068, Shaanxi Province, China
| | - Jing Lv
- Department of Clinical Laboratory, Honghui Hospital, Xi'an Jiaotong University, Xi'an 710054, Shaanxi Province, China
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Jang HR, Lee HY, Song SY, Lim KH. Clinical outcomes of targeted therapies in elderly patients aged ≥ 80 years with metastatic colorectal cancer. World J Clin Cases 2022; 10:10066-10076. [PMID: 36246797 PMCID: PMC9561573 DOI: 10.12998/wjcc.v10.i28.10066] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Revised: 07/26/2022] [Accepted: 08/17/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND The 5-fluorouracil-based chemotherapy combined with oxaliplatin or irinotecan is usually used in colorectal cancer (CRC). The addition of a targeted agent (TA) to this combination chemotherapy is currently the standard treatment for metastatic CRC. However, the efficacy and safety of combination chemotherapy for metastatic CRC in patients aged above 80 years has yet to be established.
AIM To assess the clinical outcomes and feasibility of combination chemotherapy using a TA in extremely elderly patients with CRC.
METHODS Eligibility criteria were: (1) Age above 80 years; (2) Metastatic colorectal cancer; (3) Palliative chemotherapy naïve; (4) Eastern Cooperative Oncology Group performance status 0-1; and (5) Adequate organ function. Patients received at least one dose of combination chemotherapy with or without TA. Response was evaluated every 8 wk.
RESULTS Of 30 patients, the median age of 15 patients treated with TA was 83.0 years and that of those without TA was 81.3 years. The median progression-free survival (PFS) and overall survival (OS) in patients treated with TA were 7.4 mo and 15.4 mo, respectively, compared with 4.4 mo and 15.6 mo, respectively, in patients treated without TA. There was no significant difference in PFS (P: 0.193) and OS (P: 0.748) between patients treated with and without TA. Common grade 3/4 hematologic toxicities were anemia (16.7%) and neutropenia (10.0%). After disease progression, the median OS of patients who were treated with and without salvage chemotherapy were 23.5 mo and 7.0 mo, respectively, suggesting significant difference in OS (P = 0.001).
CONCLUSION Combination chemotherapy with TA for metastatic CRC may be considered feasible in patients aged above 80 years, when with careful caution. Salvage chemotherapy can help improve OS in some selected of these elderly patients.
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Affiliation(s)
- Hee Ryeong Jang
- Department of Internal Medicine, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon-si, Gangwon-do 24289, South Korea
| | - Hui-Young Lee
- Department of Internal Medicine, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon-si, Gangwon-do 24289, South Korea
| | - Seo-Young Song
- Department of Internal Medicine, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon-si, Gangwon-do 24289, South Korea
| | - Kyu-Hyoung Lim
- Department of Internal Medicine, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon-si, Gangwon-do 24289, South Korea
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Tao W, Cheng YX, Liu XY, Zhang B, Yuan C, Peng D, Zhang W. A Simple Predictive Index of the Abdominal Shape for Postoperative Complications After Laparoscopy-Assisted Distal Gastrectomy for Gastric Cancer. Front Surg 2021; 8:768434. [PMID: 34957204 PMCID: PMC8692270 DOI: 10.3389/fsurg.2021.768434] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Accepted: 11/15/2021] [Indexed: 12/24/2022] Open
Abstract
Background: The purpose of this study was to explore the effect of abdominal shape on the short-term surgical outcomes. Methods: This was a retrospective study that included 425 patients undergoing laparoscopic distal gastrectomy plus D2 lymph node dissection (LADG) from January 2013 to January 2021. The abdominal parameters, including the shortest distance of the pancreas from the anterior abdominal skin (PAAD), the lower sternum angle (LSA), the thickness of the subcutaneous fat at the navel level (SFT), the anteroposterior diameters (APD) and the left-right diameters (LRD) at the navel level, the distance from the xiphoid process to the navel (XND) and the distance from the xiphoid process to the pubis (XBD), were calculated by preoperative abdominal computed tomography (CT) imaging. The parameters and short-term surgical outcomes were analyzed. Results: In males, the number of retrieved lymph nodes was significantly higher in patients with a lower APD group (p = 0.031). The operation time was significantly shorter in the lower body mass index (BMI) (p = 0.007), lower LSA (p = 0.035), lower PAAD (p = 0.000), lower SFT (p = 0.004), lower APD (p = 0.000) and lower LRD (p = 0.014) groups. The estimated blood loss was significantly less in the lower BMI (p = 0.035), lower LSA (p = 0.001), lower PAAD (p = 0.012), lower SFT (p = 0.003), lower APD (p = 0.000) and lower LRD (p = 0.005) groups. The complications were fewer in the lower LSA (p = 0.012), lower APD (p = 0.043) and lower LRD (p = 0.023) groups. In females, the postoperative hospital stay was shorter in the lower PAAD (p = 0.027) and lower SFT (p = 0.004) groups, and the lower SFT group had fewer complications (p = 0.020). Furthermore, in multivariate analysis, higher PAAD (p = 0.037, odds ratio = 1.030, 95% CI = 1.002-1.059) was an independent factor for predicting postoperative complications in males. Conclusion: Various abdominal shapes can affect the difficulty of LADG. Higher PAAD is a simple independent index for predicting postoperative complications in males.
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Affiliation(s)
- Wei Tao
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yu-Xi Cheng
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Xiao-Yu Liu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Bin Zhang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Chao Yuan
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Dong Peng
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Wei Zhang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
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Abusaliya A, Ha SE, Bhosale PB, Kim HH, Park MY, Vetrivel P, Kim GS. Glycosidic flavonoids and their potential applications in cancer research: a review. Mol Cell Toxicol 2021. [DOI: 10.1007/s13273-021-00178-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
Abstract
Purpose of review
Every year, the cancer patient registry increases, and the leading cause of death in a global context. Plant-based molecules are gaining attention in cancer research due to the side effects of chemotherapy. A glycosidic derivative of flavonoid (GDF) plays a significant role in cancer proliferation mechanisms. GDF inhibits cell proliferation by elevating the expression of apoptotic proteins, altering the expression of nuclear factor-kappa B (NF- κB), and decreasing mitochondrial membrane potential (Δψm) in cancer cells.
Recent findings
Reported studies on the flavonoids orientin, vitexin, prunetionoside, chrysin, and scutellarein increased attention and are being widely investigated for their potential role in different parts of cancer research. Prunetionoside is a flavonoid with high cytotoxic potential and capable of inducing necroptosis in AGS gastric cancer cells. Similarly, scutellarein is a flavonol, induces an extrinsic apoptotic pathway and downregulates the expression level of cyclin proteins in HepG2 liver cancer cells. Vitexin is reported to be capable of deregulating the expression levels of p-Akt, p-mTOR, and p-PI3K in A549 lung cancer cells. Orientin inhibits IL-8 expression and invasion in MCF-7 breast cancer cells by suppressing MMP-9 in the presence of TPA via STAT3/AP-1/ERK/PKCα-mediated signaling pathways. It also induces mitochondria-mediated intrinsic apoptosis and G0/G1 cell cycle arrest in HT29 colon cancer cells. Chrysin is a flavonoid present in honey that has been shown to play an important role in cervical and colon cancer by suppressing the AKT/mTOR/PI3K pathway and increasing ROS accumulation, LDH leakage, respectively.
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Long non-coding RNA HOXA-AS3 facilitates the malignancy in colorectal cancer by miR-4319/SPNS2 axis. J Physiol Biochem 2021; 77:653-666. [PMID: 34671931 DOI: 10.1007/s13105-021-00832-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Accepted: 07/26/2021] [Indexed: 02/07/2023]
Abstract
Growing evidence has shown the oncogenic role of long non-coding RNA HOXA-AS3 in the progression of several types of cancers, while the effect of HOXA-AS3 on colorectal cancer (CRC) remains unclear. In this study, HOXA-AS3 was significantly over-expressed in CRC clinical samples and human CRC cell lines (SW480, SW620, HCT116, COLO205, and LOVO). HOXA-AS3 knockdown was further achieved by specific siRNAs in COLO205 and LOVO cell lines. The depletion of HOXA-AS3 remarkably inhibited cell proliferation, induced cell cycle arrest, and promoted cell apoptosis in CRC cell lines. Additionally, HOXA-AS3 knockdown was determined to facilitate miR-4319 expression and reduce expression level of sphingolipid transporter 2 (SPNS2) in CRC cell lines. The dual luciferase reporter assay suggested that HOXA-AS3 acted as a sponge of miR-4319, and miR-4319 further directly targeted SPNS2 for expression regulation. Besides, HOXA-AS3 was determined to mediate CRC cell proliferation and apoptosis via miR-4319/SPNS2 axis. Moreover, tumorigenesis experiment validated that HOXA-AS3 promoted CRC progression in vivo by regulating miR-4319, SPNS2, and protein kinase B (AKT) signaling. In summary, this study reveals the novel role of HOXA-AS3 in pathogenesis of CRC and provides a candidate for CRC therapeutic target.
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Zhou C, Zhang Y, Hu X, Fang M, Xiao S. The effect of marital and insurance status on the survival of elderly patients with stage M1b colon cancer: a SEER-based study. BMC Cancer 2021; 21:891. [PMID: 34353300 PMCID: PMC8340368 DOI: 10.1186/s12885-021-08627-5] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Accepted: 07/26/2021] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Colon cancer is largely implicated in elderly patients (age ≥ 60 years). The prognosis of patients diagnosed with the M1b stage is vastly poor. Marital and insurance status has been considered important prognostic factors in various cancer types. However, how these factors influence elderly patients with stage M1b colon cancer remains to be explored. This study aims to uncover the role of marital and insurance status in the survival of elderly patients with stage M1b colon cancer. METHODS We retrieved data for patients diagnosed with stage M1b colon cancer between 2010 and 2016 from the Surveillance, Epidemiology, and End Results (SEER) database. Our analysis of the clinicopathological features, overall survival (OS), and cancer-specific survival (CSS) was based on the marital and insurance status, respectively. RESULTS In sum, 5709 stage M1b colon cancer patients with complete information from SEER were enrolled for analysis. The OS and CSS of the Non-married group were poorer compared to that of the Married group. The OS and CSS of the Uninsured group were poorer than both of the Insured group and Medicaid group. However, OS was comparable between Uninsured group and Medicaid groups. The findings allude that marital and insurance status potentially impact the long-term survival of elderly patients with M1b colon cancer. The subgroup survival analyses revealed the lowest risk for death among the Insured Married group based on the comparison of the OS and CSS across all other groups. Moreover, Univariate and multivariate analyses revealed race, marital status, surgery, and chemotherapy as independent predictors for OS, whereas insurance status, surgery,and chemotherapy were independent predictors for CSS in elderly patients with M1b colon cancer. CONCLUSION The marital and insurance status greatly impact the survival of elderly patients with M1b colon cancer. Therefore, it is imperative to provide more support to this vulnerable patient group who are lonely and uninsured, particularly in the psychological and health insurance aspect.
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Affiliation(s)
- Chenghui Zhou
- Department of general surgery, Xiangya Hospital Central South University, Central South University, Changsha, China
- Department of General, Visceral, Cancer and Transplantation Surgery, University Hospital Cologne, Cologne, Germany
| | - Yiwei Zhang
- Institute of Oncology, the First Affiliated Hospital, Hengyang Medical School, University of South, Hengyang, China
| | - Xi Hu
- Department of general surgery, Xiangya Hospital Central South University, Central South University, Changsha, China
| | - Min Fang
- Department of Gastrointestinal Surgery, the First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China.
| | - Shuai Xiao
- Institute of Oncology, the First Affiliated Hospital, Hengyang Medical School, University of South, Hengyang, China.
- Department of Gastrointestinal Surgery, the First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China.
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Park C, Lee WS, Go SI, Jeong SH, Yoo J, Cha HJ, Lee YJ, Kim HS, Leem SH, Kim HJ, Kim GS, Hong SC, Choi YH. Apoptotic Effects of Anthocyanins from Vitis coignetiae Pulliat Are Enhanced by Augmented Enhancer of the Rudimentary Homolog (ERH) in Human Gastric Carcinoma MKN28 Cells. Int J Mol Sci 2021; 22:3030. [PMID: 33809701 PMCID: PMC8002340 DOI: 10.3390/ijms22063030] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Revised: 03/08/2021] [Accepted: 03/10/2021] [Indexed: 11/17/2022] Open
Abstract
Evidence suggests that augmented expression of a certain gene can influence the efficacy of targeted and conventional chemotherapies. Here, we tested whether the high expression of enhancer of the rudimentary homolog (ERH), which serves as a prognostic factor in some cancers, can influence the efficacy of anthocyanins isolated from fruits of Vitis coignetiae Pulliat, Meoru in Korea (AIMs) on human gastric cancer cells. The anticancer efficacy of AIMs was augmented in ERH-transfected MKN28 cells (E-MKN28 cells). Molecularly, ERH augmented AIM-induced caspase-dependent apoptosis by activating caspase-3 and -9. The ERH-augmented apoptotic effect was related to mitochondrial depolarization and inhibition of antiapoptotic proteins, XIAP, and Bcl-2. In addition, reactive oxygen species (ROS) generation was augmented in AIMs-treated E-MKN28 cells compared to AIMs-treated naïve MKN28 cells. In conclusion, ERH augmented AIM-induced caspase-dependent mitochondrial-related apoptosis in MKN28 cells. A decrease in expression of Bcl-2 and subsequent excessive ROS generation would be the mechanism for ERH-augmented mitochondrial-related apoptosis in AIMs-treated MKN28 cells. A decrease in expression of XIAP would be another mechanism for ERH-augmented caspase-dependent apoptosis in AIMs-treated MKN28 cells.
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Affiliation(s)
- Cheol Park
- Division of Basic Sciences, College of Liberal Studies, Dong-eui University, Busan 47340, Korea;
| | - Won Sup Lee
- Departments of Internal Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-702, Korea;
| | - Se-Il Go
- Departments of Internal Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-702, Korea;
| | - Sang-Ho Jeong
- Departments of Surgery, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-702, Korea; (S.-H.J.); (Y.-J.L.); (S.-C.H.)
| | - Jiyun Yoo
- Department of Microbiology/Research Institute of Life Science, College of Natural Sciences, Jinju 660-701, Korea;
| | - Hee-Jae Cha
- Department of Parasitology and Genetics, Kosin University College of Medicine, Busan 49267, Korea;
| | - Young-Joon Lee
- Departments of Surgery, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-702, Korea; (S.-H.J.); (Y.-J.L.); (S.-C.H.)
| | - Heui-Soo Kim
- Department of Biological Sciences, College of Natural Sciences, Pusan National University, Busan 46241, Korea;
| | - Sun-Hee Leem
- Departments of Biology and Biomedical Science, Dong-A University, Busan 49315, Korea;
| | - Hye Jung Kim
- Departments of Pharmacology, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-702, Korea;
| | - Gon Sup Kim
- School of Veterinary Medicine, Division of Applied Life Science (BK 21 Program), Gyeongsang National University, Jinju 660-701, Korea;
| | - Soon-Chan Hong
- Departments of Surgery, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-702, Korea; (S.-H.J.); (Y.-J.L.); (S.-C.H.)
| | - Yung Hyun Choi
- Department of Biochemistry, Dong-eui University College of Korean Medicine, Busan 47227, Korea
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Yoneda A, Kuroki T, Eguchi S. Immunotherapeutic advances in gastric cancer. Surg Today 2021; 51:1727-1735. [PMID: 33590326 DOI: 10.1007/s00595-021-02236-2] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2020] [Accepted: 11/02/2020] [Indexed: 12/16/2022]
Abstract
Advanced gastric cancers are responsible for overwhelming human suffering and death. Despite the development of combination chemotherapies, the survival rates of patients with gastric cancer remain unsatisfactory. Given the growing evidence of the benefits of immunotherapy as an alternative treatment for other cancers such as advanced melanoma, non-small cell lung cancer, renal cell carcinoma, and refractory Hodgkin's lymphoma, researchers have begun to explore its application in the treatment of gastric cancer. Three types of immunotherapy have shown promising effects against gastric cancer: immune checkpoint inhibitors, chimeric antigen rector (CAR)-T cells, and tumor vaccines. Clinical trials have used either immuno-oncology monotherapies or combination immuno-chemotherapies to improve the overall survival times and objective response rates of patients with gastric cancer. We review the clinical efficacy of immunotherapy including checkpoint inhibitors, CAR‑T, and tumor vaccines, in the treatment of gastric cancer. Based on initial evidence, we believe that immunotherapy could positively impact the natural history and improve the outcomes of a subgroup of patients with gastric cancer.
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Affiliation(s)
- Akira Yoneda
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, 852-8501, Japan. .,Department of Surgery, National Hospital Organization Nagasaki Medical Center, Nagasaki, 856-0835, Japan.
| | - Tamotsu Kuroki
- Department of Surgery, National Hospital Organization Nagasaki Medical Center, Nagasaki, 856-0835, Japan
| | - Susumu Eguchi
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, 852-8501, Japan
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Abdel-Wahhab K, Elkareem H, Essawy AEN, Ashry M, Badawi M. Ameliorating and anti-inflammatory role of Balanites aegyptiaca aqueous extract on Doxorubicin-induced hepatotoxicity in male Wistar rats. EGYPTIAN PHARMACEUTICAL JOURNAL 2021. [DOI: 10.4103/epj.epj_2_21] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
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The utility of high-mobility group A2 overexpression for predicting the prognosis of gastric cancer patients and its contribution to poor prognosis via chemoresistance and the propensity for the occurrence of carcinomatosis peritonei. Surgery 2020; 169:1213-1220. [PMID: 33376002 DOI: 10.1016/j.surg.2020.11.020] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Revised: 10/22/2020] [Accepted: 11/12/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND The aim of this study was to elucidate the correlation of high-mobility group protein A2 overexpression with gastric cancer prognosis and compare its prognostic power with that of pre-existing markers. METHODS Malignant tissues from 396 patients with gastric cancer who underwent gastrectomy from 2008 to 2012 were examined. High-mobility group protein A2 expression was assessed by immunohistochemistry and the sensitivity and specificity for predicting disease progression and overall survival of high-mobility group protein A2 and the prognostic biomarkers p53, Ki-67, human epidermal growth factor receptor 2, cyclooxygenase-2, and epidermal growth factor receptor were compared. RESULTS A total of 95 samples (24.1%) showed high-mobility group protein A2 overexpression, which was related to advanced stage, undifferentiated histology, and lymphatic and perineural invasion. Additionally, high-mobility group protein A2 overexpression was an independent prognostic factor in multivariate analysis for disease progression and overall survival. Based on Kaplan-Meier survival analysis disease progression and overall survival, the high-mobility group protein A2-overexpressing patients showed worse survival. The recurrence pattern of peritoneal dissemination was more frequently observed in high-mobility group protein A2-positive group. Moreover, chemoresistance was more frequently observed in the high-mobility group protein A2-positive group. High-mobility group protein A2 exhibited a better ability for predicting disease progression and overall survival than other markers, and the prognostic power was enhanced when high-mobility group protein A2 was used with these markers. CONCLUSION High-mobility group protein A2 overexpression is associated with chemoresistance and a propensity for carcinomatosis peritonei after surgery in patients with gastric cancer. The power to predict the prognosis of patients with gastric cancer can be enhanced with the use of preexisting biomarkers and high-mobility group protein A2.
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He Y, Wang J, Ma CX, Kang YH. Role of Human Epididymis Protein 4 (HE4) in Determining Survival of Patients With Endometrial Cancer: A Meta-Analysis. Technol Cancer Res Treat 2020; 19:1533033820971660. [PMID: 33148127 PMCID: PMC7653290 DOI: 10.1177/1533033820971660] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Human epididymis protein 4 (HE4) is a novel cancer biomarker. This study evaluates the prognostic role of HE4 in determining the survival of endometrial cancer patients. METHODS Literature search was conducted in electronic databases (Embase, Ovid, PubMed, Scopus, and Web of Science). Studies were selected if they reported the relationship between HE4 and the survival of endometrial cancer patients. Random-effects meta-analyses were performed to achieve estimates of baseline serum HE4 levels, the 5-year survival with high and low serum HE4 levels/expression, and the hazard ratios (HRs) of the survival between patients with high and low serum HE4 levels. RESULTS 9 studies (1404 patients; age 63.1 years [95% confidence interval (CI): 61.2, 64.9]; follow-up 35.9 months [95% CI: 32.2, 39.6]) were included. In these patients, serum HE4 levels were 83.36 picomole/liter (pM) [95% CI: 70.15, 96.56] overall but these were higher in patients with recurrence (108.13 pM [95% CI: 63.09, 153.18] and lower in patients with no recurrence (67.88 pM [95% CI: 65.09, 70.67]). The 5-year overall survival rate was higher in patients with low HE4 levels/expression (86% [95% CI: 79, 92] but lower in patients with high HE4 levels/expression (63% [95% CI: 58, 68]. A pooled HR of survival between patients with high and low serum HE4 levels of 2.25 [95% CI: 1.56, 2.94] indicated shorter survival in patients with high serum HE4 levels. CONCLUSION High HE4 concentrations in patients with endometrial cancer are found to be associated with shorter survival.
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Affiliation(s)
- Ying He
- Department of Gynecology, The First Affiliated Hospital of Hebei North University, Zhangjiakou, China
| | - Jing Wang
- Department of Gynecology, The First Affiliated Hospital of Hebei North University, Zhangjiakou, China
| | - Chun-Xing Ma
- Department of Gynecology, The First Affiliated Hospital of Hebei North University, Zhangjiakou, China
| | - Yan-Hua Kang
- Department of Gynecology, The First Affiliated Hospital of Hebei North University, Zhangjiakou, China
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14
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Schmidtova S, Dorssers LCJ, Kalavska K, Gillis AJM, Oosterhuis JW, Stoop H, Miklikova S, Kozovska Z, Burikova M, Gercakova K, Durinikova E, Chovanec M, Mego M, Kucerova L, Looijenga LHJ. Napabucasin overcomes cisplatin resistance in ovarian germ cell tumor-derived cell line by inhibiting cancer stemness. Cancer Cell Int 2020; 20:364. [PMID: 32774158 PMCID: PMC7397611 DOI: 10.1186/s12935-020-01458-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2020] [Accepted: 07/25/2020] [Indexed: 02/08/2023] Open
Abstract
Background Cisplatin resistance of ovarian yolk sac tumors (oYST) is a clinical challenge due to dismal patient prognosis, even though the disease is extremely rare. We investigated potential association between cisplatin resistance and cancer stem cell (CSC) markers in chemoresistant oYST cells and targeting strategies to overcome resistance in oYST. Methods Chemoresistant cells were derived from chemosensitive human oYST cells by cultivation in cisplatin in vitro. Derivative cells were characterized by chemoresistance, functional assays, flow cytometry, gene expression and protein arrays focused on CSC markers. RNAseq, methylation and microRNA profiling were performed. Quail chorioallantoic membranes (CAM) with implanted oYST cells were used to analyze the micro-tumor extent and interconnection with the CAM. Tumorigenicity in vivo was determined on immunodeficient mouse model. Chemoresistant cells were treated by inhibitors intefering with the CSC properties to examine the chemosensitization to cisplatin. Results Long-term cisplatin exposure resulted in seven-fold higher IC50 value in resistant cells, cross-resistance to oxaliplatin and carboplatin, and increased migratory capacity, invasiveness and tumorigenicity, associated with hypomethylation of differentially methylated genes/promotors. Resistant cells exhibited increased expression of prominin-1 (CD133), ATP binding cassette subfamily G member 2 (ABCG2), aldehyde dehydrogenase 3 isoform A1 (ALDH3A1), correlating with reduced gene and promoter methylation, as well as increased expression of ALDH1A3 and higher overall ALDH enzymatic activity, rendering them cross-resistant to DEAB, disulfiram and napabucasin. Salinomycin and tunicamycin were significantly more toxic to resistant cells. Pretreatment with napabucasin resensitized the cells to cisplatin and reduced their tumorigenicity in vivo. Conclusions The novel chemoresistant cells represent unique model of refractory oYST. CSC markers are associated with cisplatin resistance being possible targets in chemorefractory oYST.
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Affiliation(s)
- Silvia Schmidtova
- Department of Molecular Oncology, Cancer Research Institute, Biomedical Research Center, University Science Park for Biomedicine, Slovak Academy of Sciences, Dubravska cesta 9, 845 05 Bratislava, Slovakia.,Translational Research Unit, Faculty of Medicine, Comenius University, Klenova 1, 833 10 Bratislava, Slovakia
| | - Lambert C J Dorssers
- Department of Pathology, Laboratory for Experimental Patho-Oncology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands
| | - Katarina Kalavska
- Department of Molecular Oncology, Cancer Research Institute, Biomedical Research Center, University Science Park for Biomedicine, Slovak Academy of Sciences, Dubravska cesta 9, 845 05 Bratislava, Slovakia.,Translational Research Unit, Faculty of Medicine, Comenius University, Klenova 1, 833 10 Bratislava, Slovakia.,2nd Department of Oncology, Faculty of Medicine, Comenius University and National Cancer Institute, Klenova 1, 833 10 Bratislava, Slovakia
| | - Ad J M Gillis
- Department of Pathology, Laboratory for Experimental Patho-Oncology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.,Princess Maxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, The Netherlands
| | - J Wolter Oosterhuis
- Department of Pathology, Laboratory for Experimental Patho-Oncology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands
| | - Hans Stoop
- Department of Pathology, Laboratory for Experimental Patho-Oncology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands
| | - Svetlana Miklikova
- Department of Molecular Oncology, Cancer Research Institute, Biomedical Research Center, University Science Park for Biomedicine, Slovak Academy of Sciences, Dubravska cesta 9, 845 05 Bratislava, Slovakia
| | - Zuzana Kozovska
- Department of Molecular Oncology, Cancer Research Institute, Biomedical Research Center, University Science Park for Biomedicine, Slovak Academy of Sciences, Dubravska cesta 9, 845 05 Bratislava, Slovakia
| | - Monika Burikova
- Department of Molecular Oncology, Cancer Research Institute, Biomedical Research Center, University Science Park for Biomedicine, Slovak Academy of Sciences, Dubravska cesta 9, 845 05 Bratislava, Slovakia
| | - Katarina Gercakova
- Department of Molecular Oncology, Cancer Research Institute, Biomedical Research Center, University Science Park for Biomedicine, Slovak Academy of Sciences, Dubravska cesta 9, 845 05 Bratislava, Slovakia
| | - Erika Durinikova
- Department of Molecular Oncology, Cancer Research Institute, Biomedical Research Center, University Science Park for Biomedicine, Slovak Academy of Sciences, Dubravska cesta 9, 845 05 Bratislava, Slovakia
| | - Michal Chovanec
- Translational Research Unit, Faculty of Medicine, Comenius University, Klenova 1, 833 10 Bratislava, Slovakia.,2nd Department of Oncology, Faculty of Medicine, Comenius University and National Cancer Institute, Klenova 1, 833 10 Bratislava, Slovakia
| | - Michal Mego
- Translational Research Unit, Faculty of Medicine, Comenius University, Klenova 1, 833 10 Bratislava, Slovakia.,2nd Department of Oncology, Faculty of Medicine, Comenius University and National Cancer Institute, Klenova 1, 833 10 Bratislava, Slovakia
| | - Lucia Kucerova
- Department of Molecular Oncology, Cancer Research Institute, Biomedical Research Center, University Science Park for Biomedicine, Slovak Academy of Sciences, Dubravska cesta 9, 845 05 Bratislava, Slovakia
| | - Leendert H J Looijenga
- Department of Pathology, Laboratory for Experimental Patho-Oncology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.,Princess Maxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, The Netherlands
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Lee H, Lee HH, Song KY, Park CH, Lee J. Negative Impact of Endoscopic Submucosal Dissection on Short-Term Surgical Outcomes of Subsequent Laparoscopic Distal Gastrectomy for Gastric Cancer. Ann Surg Oncol 2019; 27:313-320. [PMID: 31641951 DOI: 10.1245/s10434-019-07962-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND Endoscopic submucosal dissection (ESD) for gastric cancer produces an artificial ulcer, and negative effects on the surgical outcomes of additional gastrectomy after ESD are anticipated. The aim of this study is to analyze the effect of ESD on subsequent laparoscopic radical gastrectomy procedures and to compare the surgical results of post-ESD patients with the control group using propensity score (PS) methods. PATIENTS AND METHODS From 2013 to 2018, 1446 patients underwent totally laparoscopic distal gastrectomy in our center. Among these patients, the clinicopathological factors and short-term surgical outcomes of 107 patients who underwent ESD before surgery (the ESD group) were evaluated. A 1:4 PS matching and inverse probability weighting method was utilized to compare the short-term surgical outcomes of the ESD group with those of a matched control group. RESULTS A longer operation time was required for the patients who underwent gastrectomy earlier than 24 days after ESD than for the patients who did not. Patients whose ulcer size, due to previous ESD, exceeded 4.6 cm required longer operation times and exhibited more intraoperative blood loss than patients whose ulcer size was small. In the PS matching analysis, patients who underwent distal gastrectomy within 24 days after ESD showed more frequent postoperative morbidity than non-ESD patients. CONCLUSIONS ESD after laparoscopic distal gastrectomy is largely safe in terms of short-term surgical outcomes, but a short interval between the two procedures and a large ESD scar can make subsequent operation difficult.
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Affiliation(s)
- Hayemin Lee
- Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Han Hong Lee
- Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Kyo Young Song
- Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Cho Hyun Park
- Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Junhyun Lee
- Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul, Korea. .,Department of Surgery, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Bucheon-si, Bucheon-si, Gyeonggi-do, Korea.
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Liu J, Meng Z, Lv R, Zhang Y, Wang G, Xie J. Effect of intraoperative lung-protective mechanical ventilation on pulmonary oxygenation function and postoperative pulmonary complications after laparoscopic radical gastrectomy. ACTA ACUST UNITED AC 2019; 52:e8523. [PMID: 31166383 PMCID: PMC6556971 DOI: 10.1590/1414-431x20198523] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2019] [Accepted: 03/27/2019] [Indexed: 11/22/2022]
Abstract
This study aimed to observe the effects of lung-protective ventilation (LPV) on oxygenation index (OI) and postoperative pulmonary complications (PPCs) after laparoscopic radical gastrectomy in middle-aged and elderly patients. A total of 120 patients who were scheduled to undergo laparoscopic radical gastrectomy with an expected time of >3 h were randomly divided into conventional ventilation (CV group) with tidal volume (TV) of 10 mL/kg without positive end-expiratory pressure (PEEP), and lung-protective ventilation (PV group) with 7 mL/kg TV and personal level of PEEP with regular recruitment maneuver every 30 min. Measurements of OI, modified clinical pulmonary infection score (mCPIS), and PPCs were assessed during the perioperative period. Fifty-seven patients in the CV group and 58 in the PV group participated in the data analysis. Patients in the PV group showed better pulmonary dynamic compliance, OI, and peripheral capillary oxygen saturation during and after surgery. The mCPIS was significantly lower in the PV group than in the CV group after surgery. The incidence rate of PPCs was lower in the PV group than in the CV group and the difference was significant in patients whose ventilation time was longer than 6 h in both groups. LPV during laparoscopic radical gastrectomy significantly improved pulmonary oxygenation function and reduced postoperative mCPIS and the incidence of PPCs during the early period after surgery of middle-aged and elderly patients, especially patients whose mechanical ventilation time was longer than 6 h.
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Affiliation(s)
- Jing Liu
- Department of Anesthesia, Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Hangzhou, Zhejiang, China
| | - Zhipeng Meng
- Department of Anesthesia, Huzhou Central Hospital, Huzhou, Zhejiang, China
| | - Ran Lv
- Department of Anesthesia, Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Hangzhou, Zhejiang, China
| | - Yaping Zhang
- Department of Anesthesia, Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Hangzhou, Zhejiang, China
| | - Gaojian Wang
- Department of Anesthesia, Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Hangzhou, Zhejiang, China
| | - Junran Xie
- Department of Anesthesia, Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Hangzhou, Zhejiang, China
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EGFR Exon 19 Deletion is Associated With Favorable Overall Survival After First-line Gefitinib Therapy in Advanced Non-Small Cell Lung Cancer Patients. Am J Clin Oncol 2019; 41:385-390. [PMID: 26967328 DOI: 10.1097/coc.0000000000000282] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVES Exon 19 deletion and L858R mutation in exon 21 of the epidermal growth factor receptor (EGFR) are both common mutations that predict a good response to EGFR tyrosine kinase inhibitors in non-small cell lung cancer (NSCLC). However, the existence of clinically significant difference in sensitivity to EGFR tyrosine kinase inhibitors among different EGFR mutation subtypes is still a matter of debate. MATERIALS AND METHODS The outcome of 60 EGFR mutation-positive advanced NSCLC patients who received first-line gefitinib therapy (250 mg/d) was retrospectively analyzed according to EGFR mutation subtypes. RESULTS The median progression-free survival (PFS) and overall survival (OS) after the initiation of gefitinib therapy for all patients was 11 and 26 months, respectively. Univariate analysis showed that patients with exon 19 deletion (n=28) had significantly longer median PFS (20 vs. 8 mo, P=0.004) and OS (36 vs. 22 mo, P=0.001) compared with those with L858R mutation (n=25) and uncommon or dual mutations (n=7). Multivariate analysis revealed that exon 19 deletion (P=0.007) was an independent prognostic factor of favorable PFS, with an independent association with poor PFS of male sex (P=0.049). Exon 19 deletion was also independently associated with favorable OS (P<0.0001), whereas male sex (P=0.004) and primary metastatic disease (P=0.032) were independent prognostic factors of poor OS. CONCLUSIONS The EGFR exon 19 deletion was associated with favorable PFS and OS in patients receiving first-line gefitinib treatment. The EGFR mutation subtype should be considered when making treatment decision or designing clinical trials for chemotherapy-naive, EGFR mutation-positive advanced NSCLC patients.
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18
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Lee H, Park CH, Park SM, Kim W, Chin HM, Kim JJ, Song KY, Kim SG, Jun KH, Kim JG, Lee HH, Lee J, Kim DJ. Safety of Laparoscopic Radical Gastrectomy in Gastric Cancer Patients with End-Stage Renal Disease. J Gastric Cancer 2018; 18:287-295. [PMID: 30276005 PMCID: PMC6160531 DOI: 10.5230/jgc.2018.18.e31] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2018] [Revised: 08/25/2018] [Accepted: 09/06/2018] [Indexed: 11/20/2022] Open
Abstract
Purpose The surgical outcomes of end-stage renal disease (ESRD) patients undergoing radical gastrectomy for gastric cancer were inferior compared with those of non-ESRD patients. This study aimed to evaluate the short- and long-term surgical outcomes of ESRD patients undergoing laparoscopic gastrectomy (LG) and open gastrectomy (OG) for gastric cancer. Materials and Methods Between 2004 and 2014, 38 patients (OG: 21 patients, LG: 17 patients) with ESRD underwent gastrectomy for gastric cancer. Comparisons were made based on the clinicopathological characteristics, surgical outcomes, and long-term survival rates. Results No significant differences were noted in the clinicopathological characteristics of either group. LG patients had lower estimated blood loss volumes than OG patients (LG vs. OG: 94 vs. 275 mL, P=0.005). The operation time and postoperative hospital stay were similar in both the groups. The postoperative morbidity for LG and OG patients was 41.1% and 33.3%, respectively (P=0.873). No significant difference was observed in the long-term overall survival rates between the 2 groups (5-year overall survival, LG vs. OG: 82.4% vs. 64.7%, P=0.947). Conclusions In ESRD patients, LG yielded non-inferior short- and long-term surgical outcomes compared to OG. Laparoscopic procedures might be safely adopted for ESRD patients who can benefit from the advantages of minimally invasive surgery.
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Affiliation(s)
- Hayemin Lee
- Department of Surgery, The Catholic University of Korea St. Paul's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Cho Hyun Park
- Department of Surgery, The Catholic University of Korea St. Paul's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Seung Man Park
- Department of Surgery, The Catholic University of Korea St. Paul's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Wook Kim
- Department of Surgery, The Catholic University of Korea St. Paul's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Hyung Min Chin
- Department of Surgery, The Catholic University of Korea St. Paul's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Jin Jo Kim
- Department of Surgery, The Catholic University of Korea St. Paul's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Kyo Young Song
- Department of Surgery, The Catholic University of Korea St. Paul's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Sung Geun Kim
- Department of Surgery, The Catholic University of Korea St. Paul's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Kyong Hwa Jun
- Department of Surgery, The Catholic University of Korea St. Paul's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Jeong Goo Kim
- Department of Surgery, The Catholic University of Korea St. Paul's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Han Hong Lee
- Department of Surgery, The Catholic University of Korea St. Paul's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Junhyun Lee
- Department of Surgery, The Catholic University of Korea St. Paul's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Dong Jin Kim
- Department of Surgery, The Catholic University of Korea St. Paul's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
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Kim JH, Kim SS, Lee JH, Jung DH, Cheung DY, Chung WC, Park SH. Early Detection is Important to Reduce the Economic Burden of Gastric Cancer. J Gastric Cancer 2018; 18:82-89. [PMID: 29629223 PMCID: PMC5881013 DOI: 10.5230/jgc.2018.18.e7] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2017] [Revised: 03/18/2018] [Accepted: 03/18/2018] [Indexed: 12/15/2022] Open
Abstract
Purpose Early detection of gastric cancer is important to improve prognosis. Early detection enables local treatment, such as endoscopic submucosal dissection (ESD). Therefore, we investigated whether early detection of gastric cancer could reduce healthcare costs by comparison according to stage and treatment modalities. Materials and Methods Medical care costs were investigated according to tumor stage and initial treatment modality in 1,188 patients newly diagnosed with gastric cancer at 7 medical institutions from December 2011 to June 2012. Total medical care costs during the first-year after diagnosis (total first-year costs) were examined, including the costs of initial treatment, post-initial treatment, and inpatient and outpatient visits. Results Stage I (75.3%) was the most common cancer stage. ESD was the second most common treatment following surgery. Total first-year costs increased significantly from stages I to IV. The costs of initial treatment and post-initial treatment were lowest in patients with stage I cancer. Among patients with stage I cancer, total first-year costs were significantly lower when treated by ESD; in particular, initial ESD treatment costs were much lower than others. Conclusions The cost of healthcare has increased significantly with increasing cancer stages. ESD can greatly reduce medical care costs of gastric cancer. Thus, early detection of gastric cancer is important to reduce healthcare costs.
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Affiliation(s)
- Jie-Hyun Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Sung Soo Kim
- Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jeong Hoon Lee
- Department of Internal Medicine, University of Ulsan College of Medicine, Seoul, Korea
| | - Da Hyun Jung
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Dae Young Cheung
- Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea
| | - Woo-Chul Chung
- Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea
| | - Soo-Heon Park
- Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea
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Yoon G, Koh CW, Yoon N, Kim JY, Kim HS. Stromal p16 expression is significantly increased in endometrial carcinoma. Oncotarget 2018; 8:4826-4836. [PMID: 27902476 PMCID: PMC5354874 DOI: 10.18632/oncotarget.13594] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2016] [Accepted: 11/16/2016] [Indexed: 11/25/2022] Open
Abstract
p16 is a negative regulator of cell proliferation and is considered a tumor suppressor protein. Alterations in p16 protein expression are associated with tumor development and progression. However, the p16 expression status in the peritumoral stroma has not been investigated in the endometrium. Therefore, we evaluated stromal p16 expression in different types of endometrial lesions using immunohistochemistry. Differences in the p16 expression status according to the degree of malignancy and histological type were analyzed. This study included 62, 26, and 36 cases of benign, precancerous, and malignant endometrial lesions, respectively. Most benign lesions showed negative or weak expression, whereas precancerous lesions showed a variable degree of staining proportion and intensity. Atypical hyperplasia/endometrial intraepithelial neoplasia (AH/EIN) and serous endometrial intraepithelial carcinoma (SEIC) had significantly higher stromal p16 expression levels than benign lesions. Endometrioid carcinoma (EC), serous carcinoma (SC), and carcinosarcoma showed significantly elevated stromal p16 expression levels compared with benign and precancerous lesions. In addition, there were significant differences in stromal p16 expression between AH/EIN and SEIC and between EC and SC. In contrast, differences in stromal p16 expression among nonpathological endometrium, atrophic endometrium, endometrial polyp, and hyperplasia without atypia were not statistically significant. Our observations suggest that stromal p16 expression is involved in the development and progression of endometrial carcinoma, and raise the possibility that p16 overexpression in the peritumoral stroma is associated with aggressive oncogenic behavior of endometrial SC.
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Affiliation(s)
- Gun Yoon
- Shinsegae Women's Hospital, Daegu, Republic of Korea
| | - Chang Won Koh
- Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul, Republic of Korea
| | - Nara Yoon
- Department of Pathology, The Catholic University of Korea Incheon St. Mary's Hospital, Incheon, Republic of Korea
| | - Ji-Ye Kim
- Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hyun-Soo Kim
- Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
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Jung MK, Shin US, Ki YJ, Kim YB, Moon SM, Sung SJ. Is the Location of the Tumor Another Prognostic Factor for Patients With Colon Cancer? Ann Coloproctol 2017; 33:210-218. [PMID: 29354603 PMCID: PMC5768475 DOI: 10.3393/ac.2017.33.6.210] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2017] [Accepted: 09/24/2017] [Indexed: 12/26/2022] Open
Abstract
Purpose In this study, we investigated both the characteristics of right colon cancer (RTCC) in comparison with those of left colon cancer (LTCC) and the impact of the location of the colon cancer on the prognosis. Methods We retrospectively analyzed the cases of 974 patients with nonmetastatic colon cancer who had undergone surgery with a curative intent from January 2001 to December 2011. RTCC was defined as a tumor located proximal to the splenic flexure. The characteristics of RTCC cancer were investigated by using descriptive analyses, and their impacts on the prognosis were assessed by using a Cox multivariate regression. Results Compared to LTCC, RTCC showed a female-dominant feature, and an undifferentiated pathology was more frequently observed. The number of lymph nodes retrieved from patients with RTCC was significantly higher than that retrieved from patients with LTCC. During 75 months of follow-up, peritoneal recurrence was more common in patients with RTCC than it was in patients with LTCC, and among the patients with stage III colon cancer, the disease-free and the overall survival rates were significantly worse in patients with RTCC. After adjustments with the other prognostic factors associated with colon cancer had been made, a tumor located at the right colon was found to be independently associated with poor prognosis. Conclusion RTCC showed unique clinicopathologic features and was associated with a poorer prognosis.
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Affiliation(s)
- Myung-Kyu Jung
- Department of Surgery, Korea Cancer Center Hospital, Korea Institute of Radiological & Medical Sciences, Seoul, Korea
| | - Ui Sup Shin
- Department of Surgery, Korea Cancer Center Hospital, Korea Institute of Radiological & Medical Sciences, Seoul, Korea
| | - Young-Jun Ki
- Department of Surgery, Korea Cancer Center Hospital, Korea Institute of Radiological & Medical Sciences, Seoul, Korea
| | - Yong-Bae Kim
- Department of Surgery, Korea Cancer Center Hospital, Korea Institute of Radiological & Medical Sciences, Seoul, Korea
| | - Sun-Mi Moon
- Department of Surgery, Korea Cancer Center Hospital, Korea Institute of Radiological & Medical Sciences, Seoul, Korea
| | - Se-Jin Sung
- Department of Surgery, Korea Cancer Center Hospital, Korea Institute of Radiological & Medical Sciences, Seoul, Korea
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Choi Y, Kim A, Kim J, Lee J, Lee SY, Kim C. Optimization of RNA Extraction from Formalin-Fixed Paraffin-Embedded Blocks for Targeted Next-Generation Sequencing. J Breast Cancer 2017; 20:393-399. [PMID: 29285045 PMCID: PMC5744000 DOI: 10.4048/jbc.2017.20.4.393] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2017] [Accepted: 10/21/2017] [Indexed: 11/30/2022] Open
Abstract
Purpose Breast cancer has a high prevalence in Korea. To achieve personalized therapy for breast cancer, long-term follow-up specimens are needed for next-generation sequencing (NGS) and multigene analysis. Formalin-fixed paraffin-embedded (FFPE) samples are easier to store than fresh frozen (FF) samples. The objective of this study was to optimize RNA extraction from FFPE blocks for NGS. Methods RNA quality from FF and FFPE tissues (n=5), expected RNA amount per unit area, the relationship between archiving time and quantity/quality of FFPE-extracted RNA (n=14), differences in quantitative real-time polymerase chain reaction (qRT-PCR) and NGS results, and comparisons of both techniques with tissue processing at different institutions (n=96) were determined in this study. Results The quality of RNA did not show any statistically significant difference between paired FF and FFPE specimens (p=0.49). Analysis of tumor cellularity gave an expected RNA amount of 33.25 ng/mm2. Archiving time affected RNA quality, showing a negative correlation with RNA integrity number and a positive correlation with threshold cycle. However, RNA from samples as old as 10 years showed a 100% success rate in qRT-PCR using short primers, showing that the effect of archiving time can be overcome by proper experiment design. NGS showed a higher success rate than qRT-PCR. Specimens from institution B (n=46), which were often stored in a refrigerator for more than 6 hours and fixed without slicing, showed lower success rates and worse results than specimens from the other institutes. Conclusion Archived FFPE tissues can be used to extract RNA for NGS if they are properly processed before fixation. The expected amount of RNA per unit size calculated in this study will be useful for other researchers.
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Affiliation(s)
- Yoojin Choi
- Department of Pathology, Korea University Guro Hospital, Seoul, Korea
| | - Aeree Kim
- Department of Pathology, Korea University Guro Hospital, Seoul, Korea
| | - Jinkyoung Kim
- Department of Pathology, Korea University Guro Hospital, Seoul, Korea
| | - Jinhwan Lee
- Department of Pathology, Korea University Guro Hospital, Seoul, Korea
| | - Soo Yeon Lee
- Department of Pathology, Korea University Guro Hospital, Seoul, Korea
| | - Chungyeul Kim
- Department of Pathology, Korea University Guro Hospital, Seoul, Korea
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23
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Lu JN, Panchanathan R, Lee WS, Kim HJ, Kim DH, Choi YH, Kim GS, Shin SC, Hong SC. Anthocyanins from the Fruit of Vitis Coignetiae Pulliat Inhibit TNF-Augmented Cancer Proliferation, Migration, and Invasion in A549 Cells. Asian Pac J Cancer Prev 2017; 18:2919-2923. [PMID: 29172259 PMCID: PMC5773771 DOI: 10.22034/apjcp.2017.18.11.2919] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
Objective: Anthocyanins belong to a class of flavonoids, exhibiting antioxidant and anti-inflammatory actions have been reported to have anti-cancer effects. Here, we investigated whether anthocyanins can inhibit cancer cell proliferation, invasion, and angiogenesis in human lung cancer A549 cells, which are critically involved in cancer metastasis. Methods: We used anthocyanins from fruits of Vitis coignetiae Pulliat (AIMs) which has been used in Korean folk medicine for the treatment of inflammatory diseases and cancers. We have performed cell proliferation assays, cell invasion assay, gelatin zymography, wound healing assay and western blotting to examine whether anthocyanins can inhibit cancer cell proliferation, invasion, and angiogenesis in A549 cells. Result: AIMs did not inhibit cancer cell proliferation on A549 cells. Also, AIMs suppressed cancer migration, and invasion by supressing MMP-2 and MMP-9 expression. The Immuno-blotting results also revealed that AIMs suppressed the proteins involved in cancer proliferation (COX-2, C-myc, cyclin D1), migration and invasion (MMP-2, MMP-9), anti-apoptosis (XIAP, and c-IAP2), adhesion and angiogenesis (ICAM-1, VEGF). Conclusion: This study demonstrates that the anthocyanins isolated from fruits of Vitis coignetiae Pulliat inhibit cancer proliferation, cancer migration, and invasion that is involve in cancer-metastasis. This study provides evidence that AIMs might have anti-cancer effects on human lung cancer.
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Affiliation(s)
- Jing Nan Lu
- Department of Internal Medicine, Institute of Health Science, Gyeongsang National University School of Medicine, Jinju, 660-702 Korea.
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Procaccio L, Schirripa M, Fassan M, Vecchione L, Bergamo F, Prete AA, Intini R, Manai C, Dadduzio V, Boscolo A, Zagonel V, Lonardi S. Immunotherapy in Gastrointestinal Cancers. BIOMED RESEARCH INTERNATIONAL 2017; 2017:4346576. [PMID: 28758114 PMCID: PMC5512095 DOI: 10.1155/2017/4346576] [Citation(s) in RCA: 52] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 04/07/2017] [Accepted: 05/18/2017] [Indexed: 12/29/2022]
Abstract
Gastrointestinal cancers represent a major public health problem worldwide. Immunotherapeutic strategies are currently under investigation in this setting and preliminary results of ongoing trials adopting checkpoint inhibitors are striking. Indeed, although a poor immunogenicity for GI has been reported, a strong biological rationale supports the development of immunotherapy in this field. The clinical and translational research on immunotherapy for the treatment of GI cancers started firstly with the identification of immune-related mechanisms possibly relevant to GI tumours and secondly with the development of immunotherapy-based agents in clinical trials. In the present review a general overview is firstly provided followed by a focus on major findings on gastric, colorectal, and hepatocellular carcinomas. Finally, pathological and molecular perspectives are provided since many efforts are ongoing in order to identify possible predictive biomarkers and to improve patients' selection. Many issues are still unsolved in this field; however, we strongly believe that immunotherapy might positively affect the natural history of a subgroup of GI cancer patients improving outcome and the overall quality of life.
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Affiliation(s)
- Letizia Procaccio
- Division of Medical Oncology 1, Istituto Oncologico Veneto, IRCCS, Padova, Italy
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
| | - Marta Schirripa
- Division of Medical Oncology 1, Istituto Oncologico Veneto, IRCCS, Padova, Italy
| | - Matteo Fassan
- Department of Medicine, Surgical Pathology & Cytopathology Unit, University of Padova, Padova, Italy
| | - Loredana Vecchione
- Division of Molecular Carcinogenesis, Cancer Genomics Center Netherlands, The Netherlands Cancer Institute, Amsterdam, Netherlands
| | - Francesca Bergamo
- Division of Medical Oncology 1, Istituto Oncologico Veneto, IRCCS, Padova, Italy
| | - Alessandra Anna Prete
- Division of Medical Oncology 1, Istituto Oncologico Veneto, IRCCS, Padova, Italy
- Department of Radiological, Oncological and Pathological Sciences, Policlinico Umberto I University Hospital, Rome, Italy
| | - Rossana Intini
- Division of Medical Oncology 1, Istituto Oncologico Veneto, IRCCS, Padova, Italy
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
| | - Chiara Manai
- Division of Medical Oncology 1, Istituto Oncologico Veneto, IRCCS, Padova, Italy
- Department of Radiological, Oncological and Pathological Sciences, Policlinico Umberto I University Hospital, Rome, Italy
| | - Vincenzo Dadduzio
- Division of Medical Oncology 1, Istituto Oncologico Veneto, IRCCS, Padova, Italy
- Department of Medical Oncology, Fondazione Policlinico Universitario Agostino Gemelli, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Alice Boscolo
- Division of Medical Oncology 1, Istituto Oncologico Veneto, IRCCS, Padova, Italy
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
| | - Vittorina Zagonel
- Division of Medical Oncology 1, Istituto Oncologico Veneto, IRCCS, Padova, Italy
| | - Sara Lonardi
- Division of Medical Oncology 1, Istituto Oncologico Veneto, IRCCS, Padova, Italy
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25
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Cho J, Park Y, Baek J, Sung K. Single-incision endoscopic thyroidectomy for papillary thyroid cancer: A pilot study. Int J Surg 2017; 43:1-6. [PMID: 28502882 DOI: 10.1016/j.ijsu.2017.05.030] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2017] [Revised: 04/03/2017] [Accepted: 05/07/2017] [Indexed: 01/07/2023]
Abstract
BACKGROUND Recently, we have reported single incision endoscopic thyroidectomy using an axillary approach with gas inflation (SIET) in cases with benign thyroid tumors to reduce post-operative pain and invasiveness of the conventional endoscopic thyroidectomy. The aim of this study was to present our experiences with SIET for papillary thyroid cancer (PTC). METHODS Patients who were diagnosed with histologically papillary thyroid carcinoma (≤1 cm) with single, unilateral, and intra-thyroidal lesion and without clinical lymph node metastasis were included. We analyzed clinico-pathological characteristics, surgical outcomes, and oncologic adequacy of the SIET procedure. RESULTS Between January 2011 and July 2012, a total of 75 patients underwent hemi-thyroidectomy with ipsilateral central lymph node dissection via SIET. The mean tumor size was 0.5 cm and 4.1 ± 2.43 central lymph nodes were removed. Of the patients, 98.3% were satisfied with their surgical wound post-operatively and no critical post-operative complications occurred during the study, except for one case of post-operative bleeding. There was one case of disease recurrence, which occurred in the contra-lateral cervical lymph node region 6 months after SIET. This patient underwent completion thyroidectomy with selective neck dissection. CONCLUSION The SIET is a safe and acceptable procedure for PTC with a reduced dissection field, less post-operative pain, and more cosmetic satisfaction than conventional endoscopic thyroid surgery.
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Affiliation(s)
- Jinbeom Cho
- Department of Surgery, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea.
| | - Yohan Park
- Department of Surgery, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea.
| | - Jongmin Baek
- Department of Surgery, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea.
| | - Kiyoung Sung
- Department of Surgery, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea.
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26
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Choi YW, Choi JH. Does the efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor differ according to the type of EGFR mutation in non-small cell lung cancer? Korean J Intern Med 2017; 32:422-428. [PMID: 28352061 PMCID: PMC5432802 DOI: 10.3904/kjim.2016.190] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2016] [Accepted: 03/02/2017] [Indexed: 01/20/2023] Open
Abstract
An exon 19 deletion and a L858R mutation in exon 21 of the epidermal growth factor receptor (EGFR) are the two most common mutations that predict favorable efficacy of EGFR tyrosine kinase inhibitors (TKIs) in patients with non-small cell lung cancer (NSCLC). Many retrospective and prospective studies, as well as meta-analyses including patients with NSCLC with various lines of EGFR TKI treatment, have demonstrated longer progression-free survival and sometimes more favorable overall survival in patients with an exon 19 deletion than those with the L858R or other mutations. In contrast, some clinical studies, including phase III trials, have demonstrated no difference in the efficacy of EGFR TKIs according to the EGFR mutation type. Therefore, the existence of clinically significant differences in sensitivity to EGFR-TKIs among different EGFR mutation subtypes remains controversial. In this review, we summarize the evidence suggesting different outcomes according to the type of EGFR mutation in patients with advanced NSCLC who were treated with EGFR-TKIs, along with their clinical significance. We also discuss possible mechanisms that can explain the different sensitivities to EGFR TKIs between cases with an exon 19 deletion and those with the L858R mutation.
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Affiliation(s)
| | - Jin-Hyuk Choi
- Correspondence to Jin-Hyuk Choi, M.D. Department of Hematology-Oncology, Ajou University School of Medicine, 164 World cup-ro, Yeongtong-gu, Suwon 16499, Korea Tel: +82-31-219-4920 Fax: +82-31-219-5983 E-mail:
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27
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Kang S, Kim EO, Kim SH, Lee JH, Ahn KS, Yun M, Lee SG. Morusin induces apoptosis by regulating expression of Bax and Survivin in human breast cancer cells. Oncol Lett 2017; 13:4558-4562. [PMID: 28599457 DOI: 10.3892/ol.2017.6006] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2015] [Accepted: 02/17/2017] [Indexed: 01/07/2023] Open
Abstract
Morusin which has been isolated from the root bark of Morus alba L. (Moraceae) has previously demonstrated anticancer activity in various types of cancer cells such as hepatocellular carcinoma, glioma and prostate cancer. However, the effect of morusin on breast cancer cells remains unclear. In the present study, the potential of morusin as an anti-cancer agent in breast cancer was investigated. The results of the present study revealed that the treatment of morusin induced cell death in various human breast cancer cell lines, but exhibited little effect on normal human breast epithelial cells. In Annexin V-propidium iodide double staining assays, morusin significantly increased apoptosis in a dose-dependent manner in human breast cancer cells. The apoptosis marker proteins cleaved caspase 3 and 9 were consistently upregulated following treatment of cells with morusin in a time- and dose-dependent manner. Furthermore, morusin was demonstrated to modulate the expression of the anti-apoptotic protein Survivin and pro-apoptotic protein B-cell lymphoma 2-associated-x protein (Bax) in human breast cancer cells. These results indicate that morusin induces apoptosis by suppressing Survivin and inducing Bax proteins, suggesting that morusin is a potentially effective therapeutic agent for the treatment of patients with breast cancer.
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Affiliation(s)
- Sukmin Kang
- Department of Cancer Preventive Material Development, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea
| | - Eun-Ok Kim
- Department of Science in Korean Medicine, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.,Korean Medicine Clinical Trial Center, Kyung Hee University Korean Medicine Hospital, Seoul 05006, Republic of Korea
| | - Sung-Hoon Kim
- Department of Cancer Preventive Material Development, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.,Department of Science in Korean Medicine, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea
| | - Jun-Hee Lee
- Department of Sasang Constitutional Medicine, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.,Korean Medicine Clinical Trial Center, Kyung Hee University Korean Medicine Hospital, Seoul 05006, Republic of Korea
| | - Kwang Seok Ahn
- Department of Cancer Preventive Material Development, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.,Department of Science in Korean Medicine, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea
| | - Miyong Yun
- Department of Science in Korean Medicine, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.,Department of Bioindustry and Bioresource Engineering, College of Life Sciences, Sejong University, Seoul 05006, Republic of Korea
| | - Seok-Geun Lee
- Department of Cancer Preventive Material Development, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.,Department of Science in Korean Medicine, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.,Korean Medicine Clinical Trial Center, Kyung Hee University Korean Medicine Hospital, Seoul 05006, Republic of Korea.,KHU-KIST Department of Converging Science and Technology, Kyung Hee University, Seoul 02447, Republic of Korea
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28
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Kim DJ, Park CH, Kim W, Jin HM, Kim JJ, Lee HH, Lee JH. Safety of laparoscopic radical gastrectomy in gastric cancer patients with liver cirrhosis. Surg Endosc 2017; 31:3898-3904. [PMID: 28205032 DOI: 10.1007/s00464-017-5420-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2016] [Accepted: 01/20/2017] [Indexed: 01/04/2023]
Abstract
BACKGROUND Laparoscopic gastrectomy (LG) in gastric cancer patients with liver cirrhosis (LC) has rarely been reported. In this study, we aimed to elucidate the feasibility of LG compared with that of open gastrectomy (OG) for LC patients. METHODS Of the 75 LC patients who underwent radical gastrectomy for gastric cancer between April 2005 and March 2014, 36 patients who underwent LG were compared with 39 patients who underwent OG. Comparisons were based on clinicopathologic characteristics, surgical outcomes, and long-term survival rates. RESULTS Comparison of LG and OG revealed no significant differences in the clinicopathologic characteristics. Five patients in the LG group and eight in the OG group showed a Child-Turcotte-Pugh score (CTPs) over A. In surgical outcomes, we observed shorter operation times (191.4 ± 63.9 vs. 225.9 ± 77.1 min, p = 0.039), reduced estimated blood loss (175.5 ± 214.1 vs. 396.9 ± 514.8 ml, p = 0.021), and shorter hospital stays (10.4 ± 4.6 vs. 13.7 ± 5.8 days, p = 0.008) in LG than OG. Regarding postoperative morbidity, 7 (19.4%) and 10 (25.6%) complications were observed in the LG and OG groups, respectively. There was no difference in complications between the two groups regardless of the CTPs. One patient with a CTPs of C succumbed to hepatic failure following LG. Long-term survival and overall and recurrence-free survival rates did not differ between the two groups. CONCLUSIONS Even in cases with CTPs B, LG with lymph node dissection for gastric cancer patient was safer and acceptable than OG was. Therefore, LG can be considered an alternative surgical approach in gastric cancer with LC.
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Affiliation(s)
- Dong Jin Kim
- Department of Surgery, College of Medicine, The Catholic University of Korea, #327 Sosaro, Won-mi Gu, Bucheon, Gyeonggido, Republic of Korea
| | - Cho Hyun Park
- Department of Surgery, College of Medicine, The Catholic University of Korea, #327 Sosaro, Won-mi Gu, Bucheon, Gyeonggido, Republic of Korea
| | - Wook Kim
- Department of Surgery, College of Medicine, The Catholic University of Korea, #327 Sosaro, Won-mi Gu, Bucheon, Gyeonggido, Republic of Korea
| | - Hyung Min Jin
- Department of Surgery, College of Medicine, The Catholic University of Korea, #327 Sosaro, Won-mi Gu, Bucheon, Gyeonggido, Republic of Korea
| | - Jin Jo Kim
- Department of Surgery, College of Medicine, The Catholic University of Korea, #327 Sosaro, Won-mi Gu, Bucheon, Gyeonggido, Republic of Korea
| | - Han Hong Lee
- Department of Surgery, College of Medicine, The Catholic University of Korea, #327 Sosaro, Won-mi Gu, Bucheon, Gyeonggido, Republic of Korea
| | - Jun Hyun Lee
- Department of Surgery, College of Medicine, The Catholic University of Korea, #327 Sosaro, Won-mi Gu, Bucheon, Gyeonggido, Republic of Korea.
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29
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Kang SY, Cheon GJ, Lee M, Kim HS, Kim JW, Park NH, Song YS, Chung HH. Prediction of Recurrence by Preoperative Intratumoral FDG Uptake Heterogeneity in Endometrioid Endometrial Cancer. Transl Oncol 2017; 10:178-183. [PMID: 28167243 PMCID: PMC5293736 DOI: 10.1016/j.tranon.2017.01.002] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2016] [Revised: 12/20/2016] [Accepted: 01/05/2017] [Indexed: 02/04/2023] Open
Abstract
PURPOSE: To investigate the prognostic value of preoperative intratumoral 18F-FDG uptake heterogeneity (IFH) derived from positron emission tomography (PET)/computed tomography (CT) in patients with endometrioid endometrial cancer. METHODS: We retrospectively evaluated clinicopathological data from patients with pathologically proven endometrioid endometrial cancer who had undergone 18F-FDG PET/CT scans before surgery. Patients were divided into two groups according to their IFH. The main outcome measure was disease-free survival (DFS). RESULTS: Between January 2010 and January 2015, data from 72 patients were available for analysis. The median duration of DFS was 23 months (range, 6 to 57 months), and 4 (5.6%) patients experienced recurrence. There were significant differences in tumor size, IFH, and DFS between patients with and without recurrence. In regression analysis, high IFH value [P = .007, hazard ratio (HR) 2.545, 95% confidence interval (CI) 1.468-8.674] was the only independent risk factor for recurrence. The Kaplan-Meier survival graphs showed that DFS significantly differed in groups categorized based on IFH (P < .001, log-rank test). CONCLUSIONS: Preoperative IFH measured by 18F-FDG PET/CT was associated with recurrence of endometrioid endometrial cancer. The finding supports evidence that FDG-based heterogeneity can be a novel and useful predictor of endometrioid endometrial cancer recurrence.
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Affiliation(s)
- Seo Young Kang
- Department of Nuclear Medicine, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Gi Jeong Cheon
- Department of Nuclear Medicine, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Maria Lee
- Department of Obstetrics and Gynecology, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Hee Seung Kim
- Department of Obstetrics and Gynecology, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jae-Weon Kim
- Department of Obstetrics and Gynecology, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Noh-Hyun Park
- Department of Obstetrics and Gynecology, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Yong Sang Song
- Department of Obstetrics and Gynecology, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Hyun Hoon Chung
- Department of Obstetrics and Gynecology, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea..
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Talhouk A, McAlpine JN. New classification of endometrial cancers: the development and potential applications of genomic-based classification in research and clinical care. GYNECOLOGIC ONCOLOGY RESEARCH AND PRACTICE 2016; 3:14. [PMID: 27999680 PMCID: PMC5154099 DOI: 10.1186/s40661-016-0035-4] [Citation(s) in RCA: 125] [Impact Index Per Article: 13.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/10/2016] [Accepted: 11/22/2016] [Indexed: 01/13/2023]
Abstract
Endometrial carcinoma (EC) is the fourth most common cancer in women in the developed world. Classification of ECs by histomorphologic criteria has limited reproducibility and better tools are needed to distinguish these tumors and enable a subtype-specific approach to research and clinical care. Based on the Cancer Genome Atlas, two research teams have developed pragmatic molecular classifiers that identify four prognostically distinct molecular subgroups. These methods can be applied to diagnostic specimens (e.g., endometrial biopsy) with the potential to completely change the current risk stratification systems and enable earlier informed decision making. The evolution of genomic classification in ECs is shared herein, as well as potential applications and discussion of the essential research still needed in order to optimally integrate molecular classification in to current standard of care.
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Affiliation(s)
- A Talhouk
- Department of Pathology and Laboratory Medicine, University of British Columbia and BC Cancer Agency, Vancouver, BC Canada
| | - J N McAlpine
- Department of Gynecology and Obstetrics, Division of Gynecologic Oncology, University of British Columbia, 2775 Laurel St. 6th Floor, Vancouver, BC Canada V5Z 1M9
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Abstract
Smoking is one of the major health threats and is highly prevalent in Korea. This study quantifies the burden of disease (BOD) resulting from smoking by using the most reliable national statistics of Korea. We followed Global Burden of Disease Study (GBD) 2013 methodology for estimating BOD attributable to smoking. Population attributable fraction was calculated for all diseases and multiplied by disability-adjusted life years (DALYs) to obtain BOD by each disease. Total burden of smoking in Korea was 1 368 072 DALYs (38 per 1000); 68% of the disease burden was in males and 32% in females. The highest percentage of burden was a result of chronic obstructive pulmonary disease in both genders. BOD was highest in the 70- to 74-year-old age group. Smoking burden is substantial in Korea, especially among the elderly population. Tailored health plans for each gender and age should be formulated, and smoking-related burden should be continuously monitored to evaluate the extent of hazard and create priority settings.
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Affiliation(s)
- Aqeela Zahra
- 1 Sungkyunkwan University School of Medicine, Jangan-gu, Suwon, South Korea
| | - Hae-Kwan Cheong
- 1 Sungkyunkwan University School of Medicine, Jangan-gu, Suwon, South Korea
| | - Jae-Hyun Park
- 1 Sungkyunkwan University School of Medicine, Jangan-gu, Suwon, South Korea
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32
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Park J, Suh B, Shin DW, Hong JH, Ahn H. Cause of Death in Korean Men with Prostate Cancer: an Analysis of Time Trends in a Nationwide Cohort. J Korean Med Sci 2016; 31:1802-1807. [PMID: 27709860 PMCID: PMC5056214 DOI: 10.3346/jkms.2016.31.11.1802] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2016] [Accepted: 07/11/2016] [Indexed: 01/17/2023] Open
Abstract
Despite rapid increase in incidence of prostate cancer (PC) and PC survivors, there are few studies regarding competing causes of death and time trends in Asian population. We conducted a cohort study of 2% nationwide random sample of Korean National Health Insurance employees. A total of 873 patients who had received active treatments, including surgery, radiation therapy (RT) and androgen deprivation therapy (ADT), for newly diagnosed PC between 2003 and 2010 were included. The cause of death was categorized as PC, other cancers, cardiovascular disease, and other causes. During a median follow-up of 4.75 years, 29.4% (257/873) of the study population died. PC, other cancers, cardiovascular disease, and other causes were responsible for 46.3%, 35.4%, 6.6%, and 11.7%, respectively, of the decedents. Significant differences existed in the cause of death among treatment groups (P < 0.001). Only 20% and 9.5% of surgery and RT group died of PC, whereas 63.9% of ADT group died of PC. Other cancers were responsible for 56%, 74.6% and 17.8% of death in the surgery, RT and ADT group, respectively, while cardiovascular disease accounted for 4%, 6.3%, and 7.1% of death in the treatment groups. Analysis of time trends showed that PC-specific death tended to decrease (from 42.9% in 2003 to 23.1% in 2010), whereas non-PC causes tended to increase over the 8 years. Our results are valuable in overviewing causes of death and time trends in Korean PC patients, and planning future health policy for PC.
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Affiliation(s)
- Jinsung Park
- Department of Urology, Eulji University Hospital, Eulji University School of Medicine, Daejeon, Korea
| | - Beomseok Suh
- Department of Family Medicine, Seoul National University Hospital, Seoul, Korea
| | - Dong Wook Shin
- Department of Family Medicine, Seoul National University Hospital, Seoul, Korea
| | - Jun Hyuk Hong
- Department of Urology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Hanjong Ahn
- Department of Urology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
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Lee YH, Oh HK, Kim DW, Ihn MH, Kim JH, Son IT, Kang SI, Kim GI, Ahn S, Kang SB. Use of a Comprehensive Geriatric Assessment to Predict Short-Term Postoperative Outcome in Elderly Patients With Colorectal Cancer. Ann Coloproctol 2016; 32:161-169. [PMID: 27847786 PMCID: PMC5108662 DOI: 10.3393/ac.2016.32.5.161] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2016] [Accepted: 10/07/2016] [Indexed: 11/21/2022] Open
Abstract
Purpose This study was conducted to identify the effectiveness of a preoperative comprehensive geriatric assessment (CGA) for predicting postoperative morbidity in elderly patients who underwent surgery for colorectal cancer. Methods Elderly patients (≥70 years old) who underwent surgery for colorectal cancer at a tertiary hospital in Korea were identified, and their cases were analyzed using data from a prospectively collected database to establish an association between major postsurgical complications and 'high-risk' patient as defined by the CGA. Results A total of 240 patients, with a mean age of 76.7 ± 5.2 years, were enrolled. Ninety-five patients (39.6%) were classified as "high-risk" and 99 patients (41.3%) as having postoperative complications. The univariate analysis indicated that risk factors for postoperative complications were age, American Society of Anesthesiologists physical status classification, serum hemoglobin, carcinoembryonic antigen, cancer stage, and "high-risk" status. The multivariable analyses indicated that "high-risk" status (odds ratio, 2.107; 95% confidence interval, 1.168–3.804; P = 0.013) and elevated preoperative carcinoembryonic antigen (odds ratio, 2.561; 95% confidence interval, 1.346–4.871, P = 0.004) were independently associated with postoperative complications. A multivariable analysis of the individual CGA domains indicated that high comorbidities and low activities of daily living were significantly related with postoperative complications. Conclusion A preoperative CGA indicating "high-risk" was associated with major postoperative complications in elderly patients who underwent surgery for colorectal cancer. Thus, using the CGA to identify elderly colorectal-cancer patients who should be given more care during postoperative management may be clinically beneficial.
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Affiliation(s)
- Yoon Hyun Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Heung-Kwon Oh
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Duck-Woo Kim
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Myong Hoon Ihn
- Department of Surgery, Soonchunhyang University Gumi Hospital, Gumi, Korea
| | - Jee Hyun Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Il Tae Son
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Sung Il Kang
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Gwang Il Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Soyeon Ahn
- Division of Statistics, Medical Research Collaborating Center, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Sung-Bum Kang
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
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Jun SY, Kim SI, Lim MC, Lee JY, Lee SH, Song YJ, Chun KC, Kim JW, Park SY. Knowledge of HPV and Surgery among Women Who Underwent Cervical Conization: A Korean Multi-Center Study. Yonsei Med J 2016; 57:1222-9. [PMID: 27401655 PMCID: PMC4960390 DOI: 10.3349/ymj.2016.57.5.1222] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2015] [Revised: 01/27/2016] [Accepted: 02/17/2016] [Indexed: 11/27/2022] Open
Abstract
PURPOSE Human papillomavirus (HPV) infection is a well-known cause of cervical cancer, which, along with its precursors, can be diagnosed and treated with cervical conization (CC). This study aimed to assess HPV- and procedure-related knowledge among women who had undergone CC. MATERIALS AND METHODS Between February and May 2014, consecutive women who had undergone CC at five different educational hospitals were recruited. All patients had undergone a loop electrosurgical excision procedure as the method of CC. A survey was conducted with a self-developed, 29-item questionnaire, measuring knowledge related to HPV and CC. We analyzed the responses of 160 patients who completed the questionnaire. RESULTS Mean total knowledge scores (±standard deviation) for HPV and CC were 5.2±3.0 of a possible 13.0 and 8.3±4.2 of a possible 16.0, respectively. While 73% of the patients knew that HPV is the main cause of cervical cancer, only 44% knew that HPV is sexually transmitted. The purpose of CC was correctly identified by 71% of the patients. However, 35% failed to indicate the anatomical area resected at the time of CC in the schematic diagram. Women who were younger (p<0.001), had higher education level (p<0.001), and higher family income (p=0.008) had higher knowledge scores. In contrast, neither interval from CC to survey nor disease severity were associated with total knowledge score. CONCLUSION The level of knowledge related to HPV and CC was unexpectedly low in women who had undergone CC. Intuitive educational resources may improve this knowledge, and further cohort studies are warranted.
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Affiliation(s)
- So Yeun Jun
- Center for Uterine Cancer and Gynecologic Cancer Branch, Research Institute and Hospital, National Cancer Center, Goyang, Korea
| | - Se Ik Kim
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea
| | - Myong Cheol Lim
- Center for Uterine Cancer and Gynecologic Cancer Branch, Research Institute and Hospital, National Cancer Center, Goyang, Korea.
| | - Jung Yun Lee
- Department of Obstetrics and Gynecology, Institute of Women's Life Medical Science, Yonsei University College of Medicine, Seoul, Korea
| | - San Hui Lee
- Department of Obstetrics and Gynecology, National Health Insurance Service Ilsan Hospital, Goyang, Korea
| | - Yong Jung Song
- Department of Obstetrics and Gynecology, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Kyoung Chul Chun
- Department of Obstetrics and Gynecology, Inje University College of Medicine, Ilsan Paik Hospital, Goyang, Korea
| | - Jae Weon Kim
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea
| | - Sang Yoon Park
- Center for Uterine Cancer and Gynecologic Cancer Branch, Research Institute and Hospital, National Cancer Center, Goyang, Korea
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Kim JH, Kim BJ, Kim HS, Kim JH. Current Status and Perspective of Immunotherapy in Gastrointestinal Cancers. J Cancer 2016; 7:1599-1604. [PMID: 27698896 PMCID: PMC5039380 DOI: 10.7150/jca.16208] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2016] [Accepted: 07/09/2016] [Indexed: 12/17/2022] Open
Abstract
Cancer immunotherapy is at dawn of the Renaissance after the Medieval Dark Ages. Recent advances of understanding tumor immunology and molecular drug development are leading us to the epoch of cancer immunotherapy. Some types of immunotherapy have shown to provide survival benefit for patients with solid tumors such as malignant melanoma, renal cell carcinoma, or non-small cell lung cancer. Several studies have suggested that immune checkpoint inhibition might be effective in some patients with gastrointestinal cancers. However, the era of cancer immunotherapy in gastrointestinal cancers is still in an inchoate stage. Here we briefly review the current status and perspective of immunotherapeutic approaches in patients with gastrointestinal cancers.
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Affiliation(s)
- Jung Hoon Kim
- Division of Hemato-Oncology, Department of Internal Medicine, Hallym University Medical Center, Hallym University College of Medicine, Chuncheon, South Korea
| | - Bum Jun Kim
- Division of Hemato-Oncology, Department of Internal Medicine, Hallym University Medical Center, Hallym University College of Medicine, Chuncheon, South Korea
| | - Hyeong Su Kim
- Division of Hemato-Oncology, Department of Internal Medicine, Hallym University Medical Center, Hallym University College of Medicine, Chuncheon, South Korea
| | - Jung Han Kim
- Division of Hemato-Oncology, Department of Internal Medicine, Hallym University Medical Center, Hallym University College of Medicine, Chuncheon, South Korea
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Molecular classification of endometrial carcinoma on diagnostic specimens is highly concordant with final hysterectomy: Earlier prognostic information to guide treatment. Gynecol Oncol 2016; 143:46-53. [PMID: 27421752 DOI: 10.1016/j.ygyno.2016.07.090] [Citation(s) in RCA: 152] [Impact Index Per Article: 16.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2016] [Revised: 06/30/2016] [Accepted: 07/06/2016] [Indexed: 12/18/2022]
Abstract
OBJECTIVE Categorization and risk stratification of endometrial carcinomas is inadequate; histomorphologic assessment shows considerable interobserver variability, and risk of metastases and recurrence can only be derived after surgical staging. We have developed a Proactive Molecular Risk classification tool for Endometrial cancers (ProMisE) that identifies four distinct prognostic subgroups. Our objective was to assess whether molecular classification could be performed on diagnostic endometrial specimens obtained prior to surgical staging and its concordance with molecular classification performed on the subsequent hysterectomy specimen. METHODS Sequencing of tumors for exonuclease domain mutations (EDMs) in POLE and immunohistochemistry for mismatch repair (MMR) proteins and p53 were applied to both pre- and post-staging archival specimens from 60 individuals to identify four molecular subgroups: MMR-D, POLE EDM, p53 wild type, p53 abn (abnormal). Three gynecologic subspecialty pathologists assigned histotype and grade to a subset of samples. Concordance of molecular and clinicopathologic subgroup assignments were determined, comparing biopsy/curetting to hysterectomy specimens. RESULTS Complete molecular and pathologic categorization was achieved in 57 cases. Concordance metrics for pre- vs. post-staging endometrial samples categorized by ProMisE were highly favorable; average per ProMisE class sensitivity(0.9), specificity(0.96), PPV(0.9), NPV(0.96) and kappa statistic 0.86(95%CI, 0.72-0.93), indicating excellent agreement. We observed the highest level of concordance for 'p53 abn' tumors, the group associated with the worst prognosis. In contrast, grade and histotype assignment from original pathology reports pre- vs. post-staging showed only moderate levels of agreement (kappa=0.55 and 0.44 respectively); even with subspecialty pathology review only moderate levels of agreement were observed. CONCLUSION Molecular classification can be achieved on diagnostic endometrial samples and accurately predicts the molecular features in the final hysterectomy specimens, demonstrating concordance superior to grade and histotype. This biologically relevant information, available at initial diagnosis, has the potential to inform management (surgery, adjuvant therapy) from the earliest time point in cancer care.
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Kim HS, Ku JH, Kim SJ, Hong SJ, Hong SH, Kim HS, Kwon TG, Cho JS, Jeon SS, Joo KJ, Ahn HJ, Park HS, Seong DH, Kwon DD, Kim HJ, Lim JS, Lee HL. Prognostic Factors for Recurrence and Progression in Korean Non-Muscle-Invasive Bladder Cancer Patients: A Retrospective, Multi-Institutional Study. Yonsei Med J 2016; 57:855-864. [PMID: 27189277 PMCID: PMC4951460 DOI: 10.3349/ymj.2016.57.4.855] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2015] [Revised: 11/13/2015] [Accepted: 11/25/2015] [Indexed: 11/27/2022] Open
Abstract
PURPOSE To identify the prognostic factors related to tumor recurrence and progression in Korean patients with non-muscle-invasive bladder cancer (NMIBC). MATERIALS AND METHODS Data were collected and analyzed for 2412 NMIBC patients from 15 centers who were initially diagnosed after transurethral resection of bladder tumor (TURBT) from January 2006 to December 2010. Using univariable and multivariable Cox proportional hazards models, the prognostic value of each variable was evaluated for the time to first recurrence and progression. RESULTS With a median follow-up duration of 37 months, 866 patients (35.9%) experienced recurrence, and 137 (5.7%) experienced progression. Patients with recurrence had a median time to the first recurrence of 10 months. Multivariable analysis conducted in all patients revealed that preoperative positive urine cytology (PUC) was independently associated with worse recurrence-free survival [RFS; hazard ratio (HR) 1.56; p<0.001], and progression-free survival (PFS; HR 1.56; p=0.037). In particular, on multivariable analysis conducted for the high-risk group (T1 tumor/high-grade Ta tumor/carcinoma in situ), preoperative PUC was an independent predictor of worse RFS (HR 1.73; p<0.001) and PFS (HR 1.96; p=0.006). On multivariable analysis in patients with T1 high-grade (T1HG) cancer (n=684), better RFS (HR 0.75; p=0.033) and PFS (HR 0.33; p<0.001) were observed in association with the administration of intravesical Bacillus Calmette-Guérin (BCG) induction therapy. CONCLUSION A preoperative PUC result may adversely affect RFS and PFS, particularly in high-risk NMIBC patients. Of particular note, intravesical BCG induction therapy should be administered as an adjunct to TURBT in order to improve RFS and PFS in patients with T1HG cancer.
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Affiliation(s)
- Hyung Suk Kim
- Department of Urology, Dongguk University Ilsan Medical Center, Goyang, Korea
| | - Ja Hyeon Ku
- Department of Urology, Seoul National University College of Medicine, Seoul, Korea
| | - Se Joong Kim
- Department of Urology, Ajou University College of Medicine, Suwon, Korea
| | - Sung Joon Hong
- Department of Urology, Yonsei University College of Medicine, Seoul, Korea
| | - Sung Hoo Hong
- Department of Urology, The Catholic University College of Medicine, Seoul, Korea
| | - Hong Sup Kim
- Department of Urology, Konkuk University College of Medicine, Chungju, Korea
| | - Tae Gyun Kwon
- Department of Urology, Kyungpook National University College of Medicine, Daegu, Korea
| | - Jin Seon Cho
- Department of Urology, Hallym University College of Medicine, Chuncheon, Korea
| | - Seong Soo Jeon
- Department of Urology, Samsung Medical Center, Sungkyunkwan University College of Medicine, Seoul, Korea
| | - Kwan Joong Joo
- Department of Urology, Kangbuk Samsung Hospital, Sungkyunkwan University College of Medicine, Seoul, Korea
| | - Han Jong Ahn
- Department of Urology, Asan Medical Center, Ulsan University College of Medicine, Seoul, Korea
| | - Hong Seok Park
- Department of Urology, Korea University College of Medicine, Seoul, Korea
| | - Do Hwan Seong
- Department of Urology, Inha University College of Medicine, Incheon, Korea
| | - Dong Deuk Kwon
- Department of Urology, Chonnam National University College of Medicine, Gwangju, Korea
| | - Hyung Jin Kim
- Department of Urology, Chonbuk National University College of Medicine, Jeonju, Korea
| | - Jae Sung Lim
- Department of Urology, Chungnam National University College of Medicine, Daejeon, Korea
| | - Hyung Lae Lee
- Department of Urology, Kyung Hee University School of Medicine, Seoul, Korea.
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McAlpine JN, Temkin SM, Mackay HJ. Endometrial cancer: Not your grandmother's cancer. Cancer 2016; 122:2787-98. [DOI: 10.1002/cncr.30094] [Citation(s) in RCA: 95] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2016] [Revised: 03/11/2016] [Accepted: 03/15/2016] [Indexed: 12/20/2022]
Affiliation(s)
- Jessica N. McAlpine
- Department of Gynecology and Obstetrics, Division Gynecologic Oncology; University of British Columbia and British Columbia Cancer Agency; Vancouver British Columbia Canada
| | - Sarah M. Temkin
- Kelly Gynecologic Oncology Service, Johns Hopkins School of Medicine; Baltimore Maryland
| | - Helen J. Mackay
- Division of Medical Oncology and Hematology, Faculty of Medicine; University of Toronto, Sunnybrook Odette Cancer Center; Toronto Ontario Canada
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Jung SG, Kim JH, Kim HS, Kim KJ, Yang I. Tumor response assessment by the single-lesion measurement per organ in small cell lung cancer. Chin J Cancer Res 2016; 28:161-7. [PMID: 27199513 PMCID: PMC4865608 DOI: 10.21147/j.issn.1000-9604.2016.02.03] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
Abstract
Background: The criterion of two target lesions per organ in the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 is an arbitrary one, being supported by no objective evidence. The optimal number of target lesions per organ still needs to be investigated. We compared tumor responses using the RECIST 1.1 (measuring two target lesions per organ) and modified RECIST 1.1 (measuring the single largest lesion in each organ) in patients with small cell lung cancer (SCLC).
Methods: We reviewed medical records of patients with SCLC who received first-line treatment between January 2004 and December 2014 and compared tumor responses according to the two criteria using computed tomography.
Results: There were a total of 34 patients who had at least two target lesions in any organ according to the RECIST 1.1 during the study period. The differences in the percentage changes of the sum of tumor measurements between RECIST 1.1 and modified RECIST 1.1 were all within 13%. Seven patients showed complete response and fourteen showed partial response according to the RECIST 1.1. The overall response rate was 61.8%. When assessing with the modified RECIST 1.1 instead of the RECIST 1.1, tumor responses showed perfect concordance between the two criteria (k=1.0).
Conclusions: The modified RECIST 1.1 showed perfect agreement with the original RECIST 1.1 in the assessment of tumor response of SCLC. Our result suggests that it may be enough to measure the single largest target lesion per organ for evaluating tumor response.
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Affiliation(s)
| | | | | | | | - Ik Yang
- 3Department of Radiology, Kangnam Sacred-Heart Hospital, Hallym University Medical Center, Hallym University College of Medicine, Seoul, Republic of Korea
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Ko YS, Lee WS, Panchanathan R, Joo YN, Choi YH, Kim GS, Jung JM, Ryu CH, Shin SC, Kim HJ. Polyphenols fromArtemisia annuaL Inhibit Adhesion and EMT of Highly Metastatic Breast Cancer Cells MDA-MB-231. Phytother Res 2016; 30:1180-8. [DOI: 10.1002/ptr.5626] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2016] [Revised: 03/24/2016] [Accepted: 03/24/2016] [Indexed: 12/25/2022]
Affiliation(s)
- Young Shin Ko
- Department of Pharmacology, Institute of Health Sciences, School of Medicine; Gyeongsang National University; Jinju 660-702 South Korea
| | - Won Sup Lee
- Internal Medicine, Institute of Health Sciences, School of Medicine; Gyeongsang National University; Jinju 660-702 South Korea
| | - Radha Panchanathan
- Internal Medicine, Institute of Health Sciences, School of Medicine; Gyeongsang National University; Jinju 660-702 South Korea
| | - Young Nak Joo
- Department of Pharmacology, Institute of Health Sciences, School of Medicine; Gyeongsang National University; Jinju 660-702 South Korea
| | - Yung Hyun Choi
- Department of Biochemistry, College of Oriental Medicine, Department of Biomaterial Control (BK21 program), Graduate School; Dong-eui University; Busan 614-052 South Korea
| | - Gon Sup Kim
- School of Veterinary Medicine; Gyeongsang National University; Jinju 660-701 South Korea
| | - Jin-Myung Jung
- Neurosurgery, Institute of Health Sciences, School of Medicine; Gyeongsang National University; Jinju 660-702 South Korea
| | - Chung Ho Ryu
- Division of Applied Life Science (BK 21 Program), Institute of Agriculture and Life Science; Gyeongsang National University; Jinju 660-701 South Korea
| | - Sung Chul Shin
- Department of Chemistry, Research Institute of Life Science; Gyeongsang National University; Jinju 660-701 South Korea
| | - Hye Jung Kim
- Department of Pharmacology, Institute of Health Sciences, School of Medicine; Gyeongsang National University; Jinju 660-702 South Korea
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Han MH, Lee WS, Nagappan A, Kim HJ, Park C, Kim GY, Hong SH, Kim ND, Kim G, Ryu CH, Shin SC, Choi YH. Polyphenols from Korean prostrate spurge Euphorbia supina induce apoptosis through the Fas-associated extrinsic pathway and activation of ERK in human leukemic U937 cells. Oncol Rep 2016; 36:99-107. [PMID: 27122127 PMCID: PMC4899010 DOI: 10.3892/or.2016.4778] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2016] [Accepted: 03/10/2016] [Indexed: 11/05/2022] Open
Abstract
The Korean prostrate spurge Euphorbia supina (Euphorbiaceae family) has been used as a folk medicine in Korea against a variety of ailments such as bronchitis, hemorrhage, jaundice and multiple gastrointestinal diseases. Polyphenols from Korean E. supina (PES) which include quercetin and kaempferol derivatives have anticancer properties. Hence, we investigated the anticancer effects of PES on U937 human leukemic cells. Firstly, PES significantly inhibited the proliferation of U937 cells in a dose-dependent manner. PES induced accumulation of the sub-G1 DNA content (apoptotic cell population), apoptotic bodies and chromatin condensation and DNA fragmentation in the U937 cells. PES also induced activation of caspase-3, -8 and -9, subsequent cleavage of PARP, and significantly suppressed XIAP, cIAP-1 and cIAP-2 in a dose-dependent manner. Furthermore, PES activated Bid, and induced the loss of mitochondrial membrane potential (MMP, ΔΨm) along with upregulation of pro-apoptotic proteins (Bax and Bad), and downregulation of anti-apoptotic proteins (Bcl-2 and Bcl-xL) and cytochrome c release. The Fas receptor was upregulated by PES in a dose-dependent manner, suggesting that the extrinsic pathway was also involved in the PES-induced apoptosis. Moreover, the PES-induced apoptosis was at least in part associated with extracellular signal-regulated kinase (ERK) activation in the U937 human leukemic cells. This study provides evidence that PES may be useful in the treatment of leukemia.
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Affiliation(s)
- Min-Ho Han
- Natural Products Research Team, National Marine Biodiversity Institute of Korea, Seocheon 325-902, Republic of Korea
| | - Won Sup Lee
- Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-702, Republic of Korea
| | - Arulkumar Nagappan
- Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-702, Republic of Korea
| | - Hye Jung Kim
- Department of Pharmacology, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-702, Republic of Korea
| | - Cheol Park
- Department of Molecular Biology, College of Natural Sciences and Human Ecology, Dongeui University, Busan 614-714, Republic of Korea
| | - Gi-Young Kim
- Department of Marine Life Sciences, Jeju National University, Jeju 690-756, Republic of Korea
| | - Sang Hoon Hong
- Department of Internal Medicine, Dongeui University College of Korean Medicine, Busan 614-052, Republic of Korea
| | - Nam Deuk Kim
- Department of Pharmacy, College of Pharmacy, Pusan National University, Busan 609-735, Republic of Korea
| | - Gonsup Kim
- School of Veterinary Medicine, Research Institute of Life Science, Gyeongsang National University, Jinju 660-701, Republic of Korea
| | - Chung Ho Ryu
- Division of Applied Life Science (BK 21 Program), Research Institute of Life Science, Gyeongsang National University, Jinju 660-701, Republic of Korea
| | - Sung Chul Shin
- Department of Chemistry, Research Institute of Life Science, Gyeongsang National University, Jinju 660-701, Republic of Korea
| | - Yung Hyun Choi
- Department of Biochemistry, Dongeui University College of Korean Medicine, Busan 614-052, Republic of Korea
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Paik KH, Lee JC, Kim HW, Kang J, Lee YS, Hwang JH, Ahn SH, Park DJ, Kim HH, Kim J. Risk Factors for Gallstone Formation in Resected Gastric Cancer Patients. Medicine (Baltimore) 2016; 95:e3157. [PMID: 27082555 PMCID: PMC4839799 DOI: 10.1097/md.0000000000003157] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Previous studies reported increased incidence of gallstone formation after gastrectomy. However, there were few reports about factors other than surgical technique. The purpose of this study is to investigate the spectrum of risk factors of gallstone formation after gastrectomy. From June 2003 to December 2008, 1480 patients who underwent gastrectomy due to gastric cancer but had no gallstones before surgery were identified. Electronic medical records were retrospectively reviewed. Gallstones were assessed by computerized tomography or ultrasound performed as surveillance for recurrence. There were 987 men (66.7%) and the median age was 59.0 years. The median follow-up period was 47.0 months. According to the surgical technique, 754 (50.9%), 459 (31.1%), and 267 (18.0%) underwent subtotal gastrectomy with Billroth I (STG B-I) and Billroth II (STG B-II) anastomosis, and total gastrectomy (TG). Within the follow-up period, gallstone formation occurred in 106 of 1480 patients (7.2%), the only 9 patients (0.6%) experienced symptomatic cholecystitis. By multivariate Cox regression analysis, age (HR 1.02, 95% CI 1.00-1.04), male (1.65, 1.02-2.67), diabetes mellitus (2.15, 1.43-3.24), ≥4% decrease of body mass index after surgery (1.66, 1.02-2.70), STG B-II (1.63, 1.03-2.57), and TG (2.35, 1.43-3.24) compared with STG B-I were associated with gallstone formation. Common bile duct stone formation occurred in 20 of 1480 patients (1.4%) and was only associated with gallstones. After gastrectomy, there were considerable numbers of patients with newly developed gallstones; however, prophylactic cholecystectomy should not be routinely recommended. Gastrectomy (STG B-II or TG), old age, male sex, diabetes mellitus, and decreased body mass index were associated with gallstones.
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Affiliation(s)
- Kyu-Hyun Paik
- From the Department of Internal Medicine (K-HP, J-CL, HWK, JK, J-HH, JK); Department of Surgery (SHA, DJP, H-HK), Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam-si; and Department of Internal Medicine (YSL), Keimyung University School of Medicine, Daegu, Korea
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Park JY, Suh DS, Kim JH, Kim YM, Kim YT, Nam JH. Outcomes of fertility-sparing surgery among young women with FIGO stage I clear cell carcinoma of the ovary. Int J Gynaecol Obstet 2016; 134:49-52. [DOI: 10.1016/j.ijgo.2015.10.022] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2015] [Revised: 10/25/2015] [Accepted: 02/29/2016] [Indexed: 10/22/2022]
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Ju HM, Yu KW, Cho SD, Cheong SH, Kwon KH. Anti-cancer effects of traditional Korean wild vegetables in complementary and alternative medicine. Complement Ther Med 2016; 24:47-54. [DOI: 10.1016/j.ctim.2015.11.004] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2014] [Revised: 07/18/2015] [Accepted: 11/26/2015] [Indexed: 11/16/2022] Open
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Kim EY, Cho EN, Park HS, Hong JY, Lim S, Youn JP, Hwang SY, Chang YS. Compound EGFR mutation is frequently detected with co-mutations of actionable genes and associated with poor clinical outcome in lung adenocarcinoma. Cancer Biol Ther 2016; 17:237-45. [PMID: 26785607 PMCID: PMC4848002 DOI: 10.1080/15384047.2016.1139235] [Citation(s) in RCA: 85] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
Compound EGFR mutations, defined as double or multiple mutations in the EGFR tyrosine kinase domain, are frequently detected with advances in sequencing technology but its clinical significance is unclear. This study analyzed 61 cases of EGFR mutation positive lung adenocarcinoma using next-generation sequencing (NGS) based repeated deep sequencing panel of 16 genes that contain actionable mutations and investigated clinical implication of compound EGFR mutations. Compound EGFR mutation was detected in 15 (24.6%) of 61 cases of EGFR mutation-positive lung adenocarcinoma. The majority (12/15) of compound mutations are combination of the atypical mutation and typical mutations such as exon19 deletion, L858R or G719X substitutions, or exon 20 insertion whereas 3 were combinations of rare atypical mutations. The patients with compound mutation showed shorter overall survival than those with simple mutations (83.7 vs. 72.8 mo; P = 0.020, Breslow test). Among the 115 missense mutations discovered in the tested genes, a few number of actionable mutations were detected irrelevant to the subtype of EGFR mutations, including ALK rearrangement, BCL2L11 intron 2 deletion, KRAS c.35G>A, PIK3CA c.1633G>A which are possible target of crizotinib, BH3 mimetics, MEK inhibitors, and PI3K-tyrosine kinase inhibitors, respectively. 31 missense mutations were detected in the cases with simple mutations whereas 84 in those with compound mutation, showing that the cases with compound missense mutation have higher burden of missense mutations (P = 0.001, independent sample t-test). Compound EGFR mutations are detected at a high frequency using NGS-based repeated deep sequencing. Because patients with compound EGFR mutations showed poor clinical outcomes, they should be closely monitored during follow-up.
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Affiliation(s)
- Eun Young Kim
- a Department of Internal Medicine , Yonsei University College of Medicine , Seoul , Republic of Korea
| | - Eun Na Cho
- a Department of Internal Medicine , Yonsei University College of Medicine , Seoul , Republic of Korea
| | - Heae Surng Park
- b Pathology, Yonsei University College of Medicine , Seoul , Republic of Korea
| | - Ji Young Hong
- c Department of Bio-Nanotechnology , Hanyang University , Sangnok-gu, Ansan , Gyeonggi-do , Republic of Korea
| | | | | | - Seung Yong Hwang
- c Department of Bio-Nanotechnology , Hanyang University , Sangnok-gu, Ansan , Gyeonggi-do , Republic of Korea
| | - Yoon Soo Chang
- a Department of Internal Medicine , Yonsei University College of Medicine , Seoul , Republic of Korea
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Park S, Kim HY, Kim H, Park JH, Kim JH, Kim KH, Kim W, Choi IS, Jung YJ, Kim JS. Changes in Noninvasive Liver Fibrosis Indices and Spleen Size During Chemotherapy: Potential Markers for Oxaliplatin-Induced Sinusoidal Obstruction Syndrome. Medicine (Baltimore) 2016; 95:e2454. [PMID: 26765438 PMCID: PMC4718264 DOI: 10.1097/md.0000000000002454] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Oxaliplatin-based regimens are standard treatments for the patients with colorectal cancer (CRC) and advanced gastric cancer (AGC). However, owing to hepatic sinusoidal obstruction syndrome (SOS), the use of oxaliplatin sometimes results in splenomegaly. The aim of the present study was to evaluate the correlation between chemotherapy-associated changes of noninvasive liver fibrosis indices and volumetric changes of the spleen.From February 2004 to April 2014, patients with CRC or AGC receiving oxaliplatin-based chemotherapy were studied. The possibility of SOS development was evaluated before and after the oxaliplatin exposure with splenic volume index (SVI). Four different noninvasive liver fibrosis indices were used for risk analysis, namely age-platelet index (API), AST-to-platelet ratio index (APRI), platelet-to-spleen ratio (PSR), and fibrosis-4 score (FIB-4).A total of 275 patients were eligible for evaluation: 200 patients had CRC and 75 patients had AGC. Using the cutoff of SVI increase ≥ 0.3, 113 patients (41.1%) were positive for splenomegaly. The changes of indices significantly correlated with SVI increase. Adjusted odds ratios for those indices were as follows: API = 1.16 (95% confidential interval [CI], 1.01-1.32; P = .03); APRI = 2.45 (95% CI, 1.30-4.63; P = .01); PSR = 0.69 (95% CI, 0.59-0.80; P < .01); and FIB-4 = 1.37 (95% CI, 1.16-1.63; P < .01). Optimal cutoff values with statistical significance were calculated and suggested.The changes of noninvasive liver fibrosis indices showed a good correlation with the increase in the spleen volume during oxaliplatin-based chemotherapy. Validation of these indices for monitoring of oxaliplatin-induced hepatic SOS is warranted.
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Affiliation(s)
- Sehhoon Park
- From the Department of Internal Medicine (SP), Seoul National University Hospital, Seoul; Department of Internal Medicine (HYK, JHP, KHK, WK, ISC, YJJ, J-SK), Seoul National University Boramae Medical Center, Seoul; Department of Pathology (HK), Seoul National University Bundang Hospital, Bundang-gu, Seongnam; and Department of Pathology (JHK), Seoul National University Boramae Medical Center, Seoul, Korea
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Kim HS, Kim JH, Kim JW, Kim BC. Chemotherapy in Elderly Patients with Gastric Cancer. J Cancer 2016; 7:88-94. [PMID: 26722364 PMCID: PMC4679385 DOI: 10.7150/jca.13248] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2015] [Accepted: 11/01/2015] [Indexed: 12/23/2022] Open
Abstract
Gastric cancer (GC) is one of the most frequent malignant diseases in the elderly. Systemic chemotherapy showed an improvement of quality of life and survival benefit compared to supportive care alone in patients with advanced GC. Because comorbidities or age-related changes in pharmacokinetics and pharmacodynamics may lead to higher toxicity, however, many oncologists hesitate to recommend elderly patients to receive chemotherapy. Available data suggest that elderly patients with GC are able to tolerate and benefit from systemic chemotherapy to the same extent as younger patients. The age alone should not be the only criteria to preclude effective chemotherapy. However, proper patient selection is extremely important to deliver effective treatment safely. A comprehensive geriatric assessment (CGA) is a useful method to assess life expectancy and risk of morbidity in older patients and to guide providing optimal treatment. Treatment should be personalized based on the nature of the disease, the life expectancy, the risk of complication, and the patient's preference. Combination chemotherapy can be considered for older patients with metastatic GC who are classified as non-frail patients by CGA. For frail or vulnerable patients, however, monotherapy or only symptomatic treatment may be desirable. Targeted agents seem to be promising treatment options for elderly patients with GC considering their better efficacy and less toxicity.
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Affiliation(s)
- Hyeong Su Kim
- 1. Department of Internal Medicine, Kangnam Sacred-Heart Hospital, Hallym University Medical Center, Hallym University College of Medicine, Seoul, South Korea
| | - Jung Han Kim
- 1. Department of Internal Medicine, Kangnam Sacred-Heart Hospital, Hallym University Medical Center, Hallym University College of Medicine, Seoul, South Korea
| | - Ji Won Kim
- 2. Department of Surgery, Kangnam Sacred-Heart Hospital, Hallym University Medical Center, Hallym University College of Medicine, Seoul, South Korea
| | - Byung Chun Kim
- 2. Department of Surgery, Kangnam Sacred-Heart Hospital, Hallym University Medical Center, Hallym University College of Medicine, Seoul, South Korea
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Kim JH, Baek MJ, Ahn BK, Kim DD, Kim IY, Kim JS, Bae BN, Seo BG, Jung SH, Hong KH, Kim H, Park DG, Lee JH. Clinical Practice in the Use of Adjuvant Chemotherapy for Patients with Colon Cancer in South Korea: a Multi-Center, Prospective, Observational Study. J Cancer 2016; 7:136-43. [PMID: 26819636 PMCID: PMC4716845 DOI: 10.7150/jca.13405] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2015] [Accepted: 11/01/2015] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND Adjuvant chemotherapy is a crucial part of treatment for patients with locally advanced colon cancer. This study was conducted to investigate the actual practice in the use of adjuvant chemotherapy for patients with high-risk stage II or stage III colon cancer in South Korea. METHODS This was a 24-month open-label, prospective, observational study conducted at 12 centers across South Korea. Patients with high-risk stage II and stage III colon cancer receiving adjuvant chemotherapy after curative surgery were included, and data were collected at baseline, third, and sixth month. RESULTS A total of 246 patients were included in the analyses. Of five available regimens (FOLFOX, CAPOX, 5-FU/LV, capecitabine, and UFT/LV), FOLFOX was most commonly used (82.5%). Investigators indicated the "efficacy" as the major cause for selecting FOLFOX or CAPOX. For 5-FU/LV, capecitabine, or UFT/LV, the "safety" or "patient's characteristics (age, comorbidity, and stage)" was one of the most important selecting factors. Patients receiving 5-FU/LV, capecitabine, or UFT/LV had older age, worse PS and lower disease stage (stage II) than patients receiving FOLFOX or CAPOX. Hematologic toxicities were the most common cause of dose adjustment and treatment delay. CONCLUSIONS In South Korea, FOLFOX was the most commonly used regimen for adjuvant chemotherapy and its efficacy was the main cause for selecting this regimen. Patients receiving 5-FU/LV, capecitabine, or UFT/LV had older age, worse PS and lower disease stage (stage II) than patients receiving FOLFOX or CAPOX.
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Affiliation(s)
- Jung Han Kim
- 1. Department of Internal Medicine, Kangnam Sacred-Heart Hospital, Hallym University College of Medicine, Seoul 150-950, Korea
| | - Moo Jun Baek
- 2. Department of Surgery, Soonchunhyang University College of Medicine, Cheonan, Korea
| | - Byung-Kwon Ahn
- 3. Department of Surgery, Kosin University College of Medicine, Busan, Korea
| | - Dae Dong Kim
- 4. Department of Surgery, Daegu Catholic University Medical Center, Catholic University of Daegu School of Medicine, Daegu, Korea
| | - Ik Yong Kim
- 5. Department of Surgery, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Jin Soo Kim
- 6. Department of Surgery, College of Medicine, Chungnam National University, Daejeon, Korea
| | - Byung-Noe Bae
- 7. Department of Surgery, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, Korea
| | - Bong-Gun Seo
- 8. Department of Hemato-Oncology, Dongnam Institute of Radiological and Medical Sciences, Busan, Korea
| | - Sang Hun Jung
- 9. Department of Surgery, Yeungnam University College of Medicine, Daegu, Korea
| | - Kwan Hee Hong
- 10. Department of Surgery, Inje University Sanggye Paik Hospital, Seoul, Korea
| | - Hungdai Kim
- 11. Department of Surgery, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Dong Guk Park
- 12. Department of Surgery, Dankook University College of Medicine, Cheonan, Korea
| | - Ji Hye Lee
- 13. Medical department of sanofi-aventis Korea, Seoul, Korea
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Kim TH, Lim MC, Kim SI, Seo SS, Kim SH, Park SY. Preoperative Prediction of Cardiophrenic Lymph Node Metastasis in Advanced Ovarian Cancer Using Computed Tomography. Ann Surg Oncol 2015; 23:1302-8. [PMID: 26714941 DOI: 10.1245/s10434-015-5015-0] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2015] [Indexed: 01/20/2023]
Abstract
OBJECTIVE The aim of this study was to determine whether the preoperative diameter of cardiophrenic lymph nodes (CPLNs) along the short and long axes, determined via computed tomography (CT), predicts CPLN metastasis in patients with advanced epithelial ovarian cancer. METHODS A total of 31 patients with primary advanced ovarian cancer who had CPLN dissection underwent preoperative CT that was reviewed twice by a radiologist blinded to the final pathology. An array of CT features and clinical factors [age, cancer antigen 125 (CA 125)] were compared between metastasis-positive and metastasis-negative CPLNs using the t test and Fisher's exact test. The optimal CPLN dimensions that best predicted metastasis were calculated using a receiver operating characteristic (ROC) curve, and were applied to find the correlation with other CT findings. Results were validated in an independent test set of nine patients by using the best cutoff value to predict metastasis. RESULTS Pathological evaluation revealed metastasis-positive CPLNs in 19 patients and metastasis-negative CPLNs in 12 patients. Metastasis-positive CPLNs had significantly reduced short axes than those of negative CPLNs (5.6 ± 1.7 and 7.8 ± 2.2, respectively; p < 0.001). ROC curve analysis showed that a cutoff value of 7 mm for the short axis demonstrated the largest area under the curve (0.789; p < 0.0007), with 63.16 % sensitivity and 83.33 % specificity. The presence of peritoneal metastasis and abdominopelvic adenopathy strongly related with CPLN adenopathy. Accuracies were 66.7 % (six of nine patients) based on the cutoff value in the independent test set. CONCLUSIONS The probability of detecting CPLN metastasis in patients with advanced ovarian cancer was approximately 85 % when the short axis of the CPLN was >7 mm in preoperative CT scans. Patients with CPLNs of this size may be candidates for CPLN dissection in order to confirm the pathological diagnosis.
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Affiliation(s)
- Tae-Hyung Kim
- Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea
| | - Myong Cheol Lim
- Center for Uterine Cancer, Research Institute and Hospital, National Cancer Center, Goyang-si, Republic of Korea. .,Gynecologic Cancer Branch, Research Institute and Hospital, National Cancer Center, Goyang-si, Gyeonggi-do, Republic of Korea. .,Department of Cancer Control and Policy, Graduate School of Cancer Science and Policy, National Cancer Center, Seoul, Republic of Korea.
| | - Se Ik Kim
- Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul, Republic of Korea
| | - Sang-Soo Seo
- Center for Uterine Cancer, Research Institute and Hospital, National Cancer Center, Goyang-si, Republic of Korea
| | - Sun Ho Kim
- Center for Uterine Cancer, Research Institute and Hospital, National Cancer Center, Goyang-si, Republic of Korea
| | - Sang-Yoon Park
- Center for Uterine Cancer, Research Institute and Hospital, National Cancer Center, Goyang-si, Republic of Korea. .,Gynecologic Cancer Branch, Research Institute and Hospital, National Cancer Center, Goyang-si, Gyeonggi-do, Republic of Korea.
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Survival outcome in endometrial cancer patients according to hereditary predisposition. Taiwan J Obstet Gynecol 2015; 54:24-8. [PMID: 25675915 DOI: 10.1016/j.tjog.2014.11.003] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/30/2014] [Indexed: 12/11/2022] Open
Abstract
OBJECTIVE A familial history of ovarian cancer/breast cancer is considered a significant prognostic factor for ovarian cancer. We investigated hereditary factors by examining the incidence of synchronous malignancy in patients with endometrial cancer, and assessed the prognostic role of heredity in endometrial cancer. METHODS We retrospectively evaluated patients with endometrial cancer who underwent surgery from January 2001 to April 2011. A hereditary background in this study was defined as double primary cancer, that is, endometrial cancer accompanied by colon, ovarian, or breast cancer suggestive of Lynch syndrome, hereditary breast ovarian cancer syndrome, or Cowden syndrome, respectively. RESULTS Among 282 patients with endometrial cancer in the study population, 20 patients (7.1%) had a hereditary predisposition: 10 patients (3.5%) had ovarian cancer, six patients (2.1%) had breast cancer, and four patients (1.4%) had colon cancer. Age and lower uterine segment involvement were not statistically different between the hereditary and nonhereditary groups. The majority of the women in the hereditary group presented with Stage I cancer; however, there were no significant differences in Stage I cancer between the hereditary group and the sporadic endometrial cancer group (85% and 77%, respectively, p = 0.561). The median follow-up period was 60 months. A 5-year overall survival rate was not different between the two groups (95% and 95%, respectively, p = 0.659). Among a subgroup of patients with Stage I endometrial cancer, the 5-year overall survival rate was lower in the endometrial cancer with a hereditary predisposition group compared with the sporadic endometrial cancer group (94% and 98%, respectively, p = 0.027). CONCLUSION Seven percent of the women with endometrial cancer in our study had other malignancies such as ovarian, colon, or breast cancer synchronously. Among a subgroup of patients with Stage I cancer in the endometrial cancer with a hereditary predisposition group, the 5-year overall survival rate was significantly lower (94%). This finding should be confirmed in a larger population.
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