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Sayan M, Kankoc A, Aslan MT, Akarsu I, Kurul İC, Celik A. Recommendation for Clinical T Staging in Patients with Non-Small Cell Lung Cancer: Volumetric Measurement: A Retrospective Study from Turkey. J Chest Surg 2025; 58:51-57. [PMID: 39433483 PMCID: PMC11884980 DOI: 10.5090/jcs.24.052] [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: 05/08/2024] [Revised: 07/08/2024] [Accepted: 07/23/2024] [Indexed: 10/23/2024] Open
Abstract
Background Currently, clinical T staging in non-small cell lung cancer (NSCLC) is based on the largest radiological diameter observed on computed tomography (CT). Under this system, tumors with varying shapes-such as spherical, amorphous, or spiculated tumors- can be assigned the same T stage even with different volumes. We aimed to propose a 3-dimensional (3D) volumetric staging system for NSCLC as an alternative to diameter- based T staging and to conduct comparative survival analyses between these methods. Methods We retrospectively analyzed data from patients who underwent surgery for pT1-4N0M0 primary NSCLC between January 2018 and May 2022. Digital Imaging and Communications in Medicine data from patient CT scans were uploaded to 3D Slicer software for volumetric tumor measurement. Using the paired samples t-test or the Wilcoxon test, we compared the expected tumor volumes, calculated by tumor diameter, with the actual volumes measured by 3D Slicer. Receiver operating characteristic analysis was employed to determine the cut-off value for tumor volume. Kaplan-Meier analysis was utilized to assess overall survival, while the log-rank method was applied to compare survival differences between groups. The significance of changes in T stage was evaluated using the marginal homogeneity test. Results The study included 136 patients. Significant differences were observed between expected and actual tumor volumes (p=0.01), and associated changes in T stage were also significant (p=0.04). The survival analysis performed using tumor volume (p=0.009) yielded superior results compared to that based on diameter (p=0.04) in paients with early tumor stage. Conclusion T-factor staging based on tumor volume could represent an alternative staging method for NSCLC.
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Affiliation(s)
- Muhammet Sayan
- Department of Thoracic Surgery, Gazi University School of Medicine, Ankara, Turkey
| | - Aykut Kankoc
- Department of Thoracic Surgery, Gazi University School of Medicine, Ankara, Turkey
| | - Muhammet Tarik Aslan
- Department of Thoracic Surgery, Gazi University School of Medicine, Ankara, Turkey
| | - Irmak Akarsu
- Department of Thoracic Surgery, Gazi University School of Medicine, Ankara, Turkey
| | - İsmail Cuneyt Kurul
- Department of Thoracic Surgery, Gazi University School of Medicine, Ankara, Turkey
| | - Ali Celik
- Department of Thoracic Surgery, Gazi University School of Medicine, Ankara, Turkey
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Takano Y, Kodera K, Tsukihara S, Takahashi S, Yasunobu K, Kanno H, Ishiyama S, Saito R, Hanyu N, Eto K. Association of a newly developed Cancer Cachexia Score with survival in Stage I-III colorectal cancer. Langenbecks Arch Surg 2023; 408:145. [PMID: 37043018 DOI: 10.1007/s00423-023-02883-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Accepted: 04/03/2023] [Indexed: 04/13/2023]
Abstract
PURPOSE Cancer cachexia, a complex multifactorial syndrome associated with sarcopenia, negatively affects the quality of life and survival in patients with several cancers. We aimed to develop a new score for cachexia assessment and evaluate its effectiveness in the classification of patients undergoing radical resection for colorectal cancer. METHODS This study included 396 patients who underwent radical resection for Stage I-III colorectal cancer. To develop the Cancer Cachexia Score (CCS), we analyzed predictive factors of cachexia status related to the development of sarcopenia and incorporated significant factors into the score. We then evaluated the relationship between CCS and survival after radical resection for colorectal cancer. RESULTS As body mass index (P < 0.001), prognostic nutritional index (P = 0.005), and tumor volume (P < 0.001) were significantly associated with the development of sarcopenia, these factors were included in CCS. Using CCS, 221 (56%), 98 (25%), and 77 (19%) patients were diagnosed with mild, moderate, and severe cancer cachexia, respectively. In multivariate analysis, severe CCS (P < 0.001), N stage 1-2 (P < 0.001), and occurrence of postoperative complications (P = 0.007) were independent predictors of disease-free survival. Age ≥ 65 years (P = 0.009), severe CCS (P < 0.001), and N stage 1-2 (P < 0.001) were independent predictors of overall survival. CONCLUSIONS CCS may be a useful prognostic factor for predicting poor survival after radical resection in patients with Stage I-III colorectal cancer.
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Affiliation(s)
- Yasuhiro Takano
- Department of Surgery, Tokyo General Hospital, 3-15-2, Ekoda, Nakano, Tokyo, 165-8906, Japan.
| | - Keita Kodera
- Department of Surgery, Kasai Shoikai Hospital, Tokyo, Japan
| | - Shu Tsukihara
- Department of Surgery, Tokyo General Hospital, 3-15-2, Ekoda, Nakano, Tokyo, 165-8906, Japan
| | - Sumika Takahashi
- Department of Surgery, Tokyo General Hospital, 3-15-2, Ekoda, Nakano, Tokyo, 165-8906, Japan
| | - Kobayashi Yasunobu
- Department of Surgery, Tokyo General Hospital, 3-15-2, Ekoda, Nakano, Tokyo, 165-8906, Japan
| | - Hironori Kanno
- Department of Surgery, Tokyo General Hospital, 3-15-2, Ekoda, Nakano, Tokyo, 165-8906, Japan
| | | | - Ryota Saito
- Department of Surgery, Kasai Shoikai Hospital, Tokyo, Japan
| | - Nobuyoshi Hanyu
- Department of Surgery, Tokyo General Hospital, 3-15-2, Ekoda, Nakano, Tokyo, 165-8906, Japan
| | - Ken Eto
- Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan
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Fan WD, Chen T, Liu PJ. NIMA related kinase 2 promotes gastric cancer cell proliferation via ERK/MAPK signaling. World J Gastroenterol 2019; 25:2898-2910. [PMID: 31249448 PMCID: PMC6589739 DOI: 10.3748/wjg.v25.i23.2898] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2019] [Revised: 04/27/2019] [Accepted: 05/18/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND NIMA related kinase 2 (NEK2) is closely related to mitosis, and it is currently considered to be over-expressed frequently in many poorly prognostic cancers. However, the effect of the up-regulated NEK2 on cellular signaling in tumors, such as gastric cancer (GC), is con-fusing.
AIM To determine the role of the up-regulation of NEK2 in GC.
METHODS To investigate the pathological significance of NEK2 in GC, the expression pattern of NEK2 in GC was investigated based on the “Oncomain” database and compared between 30 pairs of cancer samples and adjacent tissues. The co-expression of NEK2 and ERK in GC was analyzed using The Cancer Genome Atlas (TCGA) database and confirmed in clinical samples by quantitative real-time PCR (qRT-PCR), and the survival curve was also plotted. Western blot or qRT-PCR was used to analyze the effect of NEK2 on the phosphorylation levels of ERK and c-JUN in two GC cell lines (BGC823 and SGC7901) with NEK2 overexpression, and the expression of the downstream effector cyclin D1. Furthermore, CCK8, EdU incorporation assay, and flow cytometry were used to detect the proliferative ability of BGC823 and SGC7901 cells with stably silenced ERK.
RESULTS NEK2 was significantly up-regulated in human GC tissues. ERK was significantly associated with NEK2 expression in human clinical specimens, and combined overexpression of NEK2 and ERK potentially forecasted a poor prognosis and survival in GC patients. NEK2 knockdown in GC cells inhibited ERK and c-JUN phosphory-lation and reduced the transcription of cyclin D1. More interestingly, NEK2 can rescue the inhibition of cellular viability, proliferation, and cell cycle progression due to ERK knockdown.
CONCLUSION Our results indicate that NEK2 plays a carcinogenic role in the malignant proliferation of GC cells via the ERK/MAPK signaling, which may be important for treatment and improving patient survival.
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Affiliation(s)
- Wei-Dong Fan
- Department of Gastroenterology, the Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang 215600, Jiangsu Province, China
| | - Tao Chen
- Department of Gastroenterology, the Wujin Hospital Affiliated to Jiangsu University, Changzhou 213002, Jiangsu Province, China
| | - Peng-Jun Liu
- Department of Gastroenterology, the Wujin Hospital Affiliated to Jiangsu University, Changzhou 213002, Jiangsu Province, China
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Hwang KT, Han W, Lee SM, Choi J, Kim J, Rhu J, Kim YA, Noh DY. Prognostic influence of 3-dimensional tumor volume on breast cancer compared to conventional 1-dimensional tumor size. Ann Surg Treat Res 2018; 95:183-191. [PMID: 30310801 PMCID: PMC6172357 DOI: 10.4174/astr.2018.95.4.183] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2017] [Revised: 04/22/2018] [Accepted: 06/01/2018] [Indexed: 12/30/2022] Open
Abstract
Purpose The prognostic influence of 3-dimensional tumor volume (Tv) on breast cancer compared to conventional 1-dimensional tumor size (T) was investigated. Methods Analysis was performed on a cohort of 8,996 primary breast cancer patients who were initially diagnosed with TNM stage I–III. Tumor size was defined as the maximum tumor dimension, and Tv was calculated by the equation of (4π × r1 × r2 × r3)/3; r1, r2, and r3 were defined as half of the largest, intermediate, and shortest dimension of the tumor, respectively. Tv was classified into Tv1, Tv2, and Tv3 according to the cut off values of 2.056 cm3 and 20.733 cm3. Results The survival curves according to both the T and Tv categories were clearly differentiated (all P < 0.001), as were those for staging by T and Tv (all P < 0.001). In T1 and T2 tumors, the Tv1 group showed superior survival over the Tv2 group (T1, P < 0.001; T2, P = 0.001). Univariate and multivariate analysis both indicated that Tv was a significant prognostic factor (both P < 0.001). The receiver operating characteristic curve showed that the area under the curves were 0.712 (P < 0.001) for Tv and 0.699 (P < 0.001) for T. Positive correlations were observed between the number of positive nodes and T (coefficient = 0.325; P < 0.001), and between the number of positive nodes and Tv (coefficient = 0.321; P < 0.001). Conclusion Tv classification works well for predicting the prognosis of breast cancer, and it is a better predictor than conventional T classification in several aspects. Further studies are needed to validate the practical usefulness of Tv classification in clinical settings.
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Affiliation(s)
- Ki-Tae Hwang
- Department of Surgery, Seoul Metropolitan Government - Seoul National University Boramae Medical Center, Seoul, Korea
| | - Wonshik Han
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | | | | | - Jongjin Kim
- Department of Surgery, Seoul Metropolitan Government - Seoul National University Boramae Medical Center, Seoul, Korea
| | - Jiyoung Rhu
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Young A Kim
- Department of Pathology, Seoul Metropolitan Government - Seoul National University Boramae Medical Center, Seoul, Korea
| | - Dong-Young Noh
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
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Dang SC, Fan YY, Cui L, Chen JX, Qu JG, Gu M. PLK1 as a potential prognostic marker of gastric cancer through MEK-ERK pathway on PDTX models. Onco Targets Ther 2018; 11:6239-6247. [PMID: 30288059 PMCID: PMC6163028 DOI: 10.2147/ott.s169880] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Background PLK1 has been identified as having a great effect on cell division and maintaining genomic stability in mitosis, spindle assembly, and DNA damage response by current studies. Materials and methods We assessed PLK1 expression in cervical cancer tissues and cells. We have also evaluated the effects of PLK1 on gastric cancer cell proliferation, migration, and apoptosis both in vitro and in vivo. Results Our results show that PLK1 is overexpressed in gastric cancer tissues and cells. Inhibition of PLK1 contributes cell cycle G2-phase arrest and inhibits the proliferation, migration, and apoptosis of gastric cancer (GC) cells, whereas its overexpression promotes proliferation, migration, and apoptosis in these cells. Moreover, PLK1 inhibition reduces expression of pMEK and pERK. More importantly, in vivo by analyzing tumorigenesis in patient-derived tumor xenograft (PDTX) models, the inhibition of PLK1 activity by BI6727 significantly decreased the volume and weight of the tumors compared with control group (P<0.01). Conclusion Our results found that PLK1 has a significant impact on the survival of GC cells; it may become a prognostic judge, a potential therapeutic target, and a preventative biomarker of GC.
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Affiliation(s)
- Sheng-Chun Dang
- Department of General Surgery, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, People's Republic of China
| | - Yi-Yi Fan
- Department of General Surgery, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, People's Republic of China
| | - Lei Cui
- Department of General Surgery, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, People's Republic of China
| | - Ji-Xiang Chen
- Department of General Surgery, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, People's Republic of China
| | - Jian-Guo Qu
- Department of General Surgery, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, People's Republic of China
| | - Min Gu
- Zhenjiang Integrative Medicine Hospital, Zhenjiang, Jiangsu Province, People's Republic of China,
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Measurement of tumor volume is not superior to diameter for prediction of lymph node metastasis in early gastric cancer with minute submucosal invasion. Oncotarget 2017; 8:113758-113765. [PMID: 29371944 PMCID: PMC5768361 DOI: 10.18632/oncotarget.22894] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2017] [Accepted: 11/13/2017] [Indexed: 01/18/2023] Open
Abstract
Background/Aim The current indication for endoscopic resection in early gastric cancer (EGC) with minute (< 500 µm) submucosal invasion is based on tumor diameter, which may be insufficient to predict lymph node metastasis (LNM). We investigated whether tumor volume might more accurately predict LNM in EGC with minute submucosal invasion. Materials and Methods Among patients who underwent gastrectomy for gastric cancer, 346 with well/moderately differentiated EGC with submucosal invasion <500 µm were evaluated. Three-dimensional tumor volume was calculated using an endoscopically resected specimen and compared with 1-dimensional tumor diameter. Predictive ability of tumor diameter or volume for LNM was evaluated using receiver operating characteristic curve analysis. Results Tumor diameter and volume predicted LNM with an area under the curve (AUC) of 0.567 and 0.589, respectively. AUC, sensitivity, specificity, positive and negative predictive values, and accuracy of the 2 models were not significantly different. Tumor diameter ≥ 3 cm showed a significant association with LNM (odds ratio [OR], 2.57; 95% confidence interval [CI], 1.01–6.57; P = 0.049), whereas a tumor volume cutoff value of 752.8 cm3 showed no significant association with LNM (OR, 1.52; 95% CI, 0.59–3.88; P = 0.385). Conclusions Tumor volume had no advantage over diameter for predicting LNM in well/moderately differentiated EGC with minute submucosal invasion.
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