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Deng MC, Chen K, Bao QM, Huang YX, Zhang CK, Zhong YK, He HY, Zu D, Liang C, Liu HD, Hu YC, Liu GX, He YH, Wu WX, Zhou JN, Teng YS, Jing J, Shi Y, Chung CYS, Yu CH, Du YA, Ye Z, Cheng XD. Evaluating log odds of positive lymph nodes as a prognostic tool in differentiated gastric cancer: A retrospective study. World J Gastroenterol 2025; 31:107029. [DOI: 10.3748/wjg.v31.i21.107029] [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: 03/13/2025] [Revised: 04/23/2025] [Accepted: 05/19/2025] [Indexed: 06/06/2025] Open
Abstract
BACKGROUND The log odds of positive lymph nodes (LODDS) are correlated with survival outcomes in gastric cancer (GC) patients. However, the prognostic value across different tumor differentiation levels remains unclear.
AIM To evaluate the independent prognostic value of LODDS and the stratified predictive efficacy in GC patients with different histologic differentiations.
METHODS We conducted a retrospective analysis of 2103 GC patients who underwent radical gastrectomy at Zhejiang Cancer Hospital. The prognostic value of LODDS was compared with that of other lymph node-based metrics, including the pathologic N stage, number of positive lymph nodes, number of total lymph nodes, and lymph node ratio, stratified by tumor differentiation.
RESULTS LODDS was identified as an independent prognostic factor for overall survival in moderately to poorly differentiated GC patients. LODDS demonstrated superior predictive accuracy over other lymph node metrics. A nomogram incorporating LODDS, age, carbohydrate antigen (CA) 125, carcinoembryonic antigen, and tumor differentiation showed good predictive accuracy (C-index = 0.703). A higher LODDS was significantly associated with an increased risk of recurrence or metastasis, poorly differentiated tumors, advanced cancer, mucinous gastric adenocarcinoma, nerve invasion, and vascular tumor thrombus. Additionally, LODDS was positively correlated with the tumor markers CA19-9, CA72-4, CA125, and CA242 (all P < 0.05).
CONCLUSION LODDS is an independent prognostic indicator for patients with moderately and poorly differentiated GC, and its predictive performance is superior to that of other models.
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Affiliation(s)
- Ming-Cong Deng
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou 310022, Zhejiang Province, China
- Hangzhou Medical College, Hangzhou 310013, Zhejiang Province, China
| | - Ken Chen
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou 310022, Zhejiang Province, China
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang Province, China
- Department of Otorhinolaryngology, Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University, Hangzhou 310006, Zhejiang Province, China
| | - Qi-Mei Bao
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou 310022, Zhejiang Province, China
| | - Yi-Xing Huang
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou 310022, Zhejiang Province, China
- Department of Otorhinolaryngology, Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University, Hangzhou 310006, Zhejiang Province, China
- School of Medicine, Zhejiang University, Hangzhou 310058, Zhejiang Province, China,
| | - Chun-Kai Zhang
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou 310022, Zhejiang Province, China
| | - Yu-Ke Zhong
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou 310022, Zhejiang Province, China
| | - Han-Yi He
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou 310022, Zhejiang Province, China
| | - Dan Zu
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou 310022, Zhejiang Province, China
- School of Life Sciences, Tianjin University, Tianjin 300100, China
| | - Chen Liang
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou 310022, Zhejiang Province, China
| | - Hai-Dong Liu
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou 310022, Zhejiang Province, China
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou 310022, Zhejiang Province, China
- Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou 310022, Zhejiang Province, China
| | - Yang-Chan Hu
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou 310022, Zhejiang Province, China
| | - Guo-Xia Liu
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou 310022, Zhejiang Province, China
- School of Life Sciences, Tianjin University, Tianjin 300100, China
| | - Yan-Hua He
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou 310022, Zhejiang Province, China
| | - Wei-Xing Wu
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou 310022, Zhejiang Province, China
| | - Jing-Nan Zhou
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou 310022, Zhejiang Province, China
| | - Yao-Shu Teng
- Department of Otorhinolaryngology, Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University, Hangzhou 310006, Zhejiang Province, China
| | - Ji Jing
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou 310022, Zhejiang Province, China
| | - Yin Shi
- School of Medicine, Zhejiang University, Hangzhou 310058, Zhejiang Province, China,
| | - Clive Yik-Sham Chung
- School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- Department of Pathology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Chen-Huan Yu
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou 310022, Zhejiang Province, China
| | - Yi-An Du
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou 310022, Zhejiang Province, China
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou 310022, Zhejiang Province, China
- Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou 310022, Zhejiang Province, China
| | - Zu Ye
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou 310022, Zhejiang Province, China
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou 310022, Zhejiang Province, China
- Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou 310022, Zhejiang Province, China
| | - Xiang-Dong Cheng
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou 310022, Zhejiang Province, China
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou 310022, Zhejiang Province, China
- Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou 310022, Zhejiang Province, China
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Dehal A, Woo Y, Glazer ES, Davis JL, Strong VE. D2 Lymphadenectomy for Gastric Cancer: Advancements and Technical Considerations. Ann Surg Oncol 2025; 32:2129-2140. [PMID: 39589578 DOI: 10.1245/s10434-024-16545-6] [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: 09/09/2024] [Accepted: 11/05/2024] [Indexed: 11/27/2024]
Abstract
Lymphadenectomy (LND) is a crucial component of the curative surgical treatment of gastric cancer (GC). The LND serves to both accurately stage the disease and offer therapeutic benefits. At the time of "curative-intent" gastrectomy, D2 LND is the optimal treatment for patients with locally advanced GC due to its survival benefits and acceptable morbidity. Mastery of the technical aspects of LND, especially D2, requires significant training, adequate case volume, and expertise. This review discusses key aspects of D2 LND, including its status as the standard treatment for locally advanced GC, definition and anatomic borders, technical details, and controversial topics such as splenic hilar dissection and omentectomy. The application of indocyanine green (ICG) fluorescence imaging to elucidate the drainage patterns of GC and to facilitate lymph node (LN) identification is briefly reviewed. Finally, GC standardization and centralization, including surgical treatment, are discussed.
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Affiliation(s)
- Ahmed Dehal
- Department of General Surgery, Southern California Permanente Medical Group, Department of Clinical Sciences, Kaiser Permanente School of Medicine, Los Angeles, CA, USA.
| | - Yanghee Woo
- Division of Surgical Oncology, Department of Surgery, City of Hope Comprehensive Cancer Center, Duarte, CA, USA
| | - Evan S Glazer
- Department of Surgery, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Jeremey L Davis
- Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Vivian E Strong
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
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3
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Miciak M, Jurkiewicz K, Dzierżek P, Rudno-Rudzińska J, Kielan W. Prognostic Significance of Lymph Node Ratio (LNR) in Gastric Cancer in Predicting Postoperative Complications and Survival: A Single-Center Study. Cancers (Basel) 2025; 17:743. [PMID: 40075592 PMCID: PMC11899347 DOI: 10.3390/cancers17050743] [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: 02/04/2025] [Revised: 02/18/2025] [Accepted: 02/21/2025] [Indexed: 03/14/2025] Open
Abstract
BACKGROUND/OBJECTIVES The Lymph Node Ratio (LNR) index is the proportion of lymph nodes with present metastases to lymph nodes removed and examined. This is an additionally established parameter for predicting the prognosis of gastric cancer patients. The most popular cancer classification, TNM, describes only the number of affected lymph nodes. It can result in a negative overestimation of the prognosis of patients with gastric cancer if the number of nodes examined is relatively limited. METHODS In this study, we retrospectively analyzed 194 patients diagnosed with gastric cancer operated on between 2017 and 2021 at the Clinical Department of Oncological Surgery, University Centre of General and Oncological Surgery of the University Clinical Hospital in Wroclaw. In total, 133 patients underwent gastrectomy with D2 lymphadenectomy and 61 remaining patients had the resection procedure abandoned due to an unresectable lesion. The LNR index was calculated based on histopathological examination, and postoperative complications were assessed using the Clavien-Dindo (C-D) scale. Statistical analysis was performed regarding the dependence of LNR on the following patient characteristics: sex, age, TNM features, tumor stage, tumor location, performed procedure, chemotherapy application, C-D complication rate, and survival rate. RESULTS The value of the LNR index significantly depends on TNM features (p < 0.05), clinical tumor stage (p < 0.05), and patient survival (p < 0.05), while no statistically significant relationship with C-D complication rate was demonstrated. CONCLUSIONS The LNR index is a relevant parameter in predicting prognosis and survival time in gastric cancer patients, but future studies on larger and differentiated groups of patients could further confirm its usefulness in the development of guidelines.
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Affiliation(s)
- Michał Miciak
- Clinical Department of Oncological Surgery, University Centre of General and Oncological Surgery, Faculty of Medicine, Wroclaw Medical University, 50-556 Wrocław, Poland; (K.J.); (J.R.-R.); (W.K.)
| | | | - Przemysław Dzierżek
- Clinical Department of Oncological Surgery, University Centre of General and Oncological Surgery, Faculty of Medicine, Wroclaw Medical University, 50-556 Wrocław, Poland; (K.J.); (J.R.-R.); (W.K.)
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4
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Hwang J, Carr J. Lymphadenectomy for Gastric Cancer. Surg Clin North Am 2025; 105:47-54. [PMID: 39523075 DOI: 10.1016/j.suc.2024.06.005] [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] [Indexed: 11/16/2024]
Abstract
Current treatment for gastric cancer includes a multidisciplinary approach of systemic therapy and surgery. While retrospective, prospective, and randomized trials have demonstrated conflicting results on the need for extended lymphadenectomy, current guidelines dictate a recommendation for the retrieval of at least 16 lymph nodes to accurately stage patients. The "D1" lymph nodes along the major gastric and epiploic vessels may provide adequate lymph node harvest, though "D2" lymphadenectomy along the celiac axis and its branches may be necessary. Performing a distal pancreatectomy and splenectomy to maximize the D2 nodal harvest is not necessary and leads to increased morbidity.
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Affiliation(s)
- Jenny Hwang
- Lewis Katz School of Medicine at St Lukes University Health Network, 800 Ostrum Street, Bethlehem, PA 18015, USA
| | - Jacquelyn Carr
- Lewis Katz School of Medicine at St Lukes University Health Network, 800 Ostrum Street, Bethlehem, PA 18015, USA; Temple University School of Medicine, Bethlehem, PA, USA.
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5
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Zheng J, Zheng L, Wang X, Mao X, Wang Q, Yang Y, Mo D. The Clinical Value of the Combined Detection of Systemic Immune-Inflammation Index (SII), Systemic Inflammation Response Index (SIRI), and Prognostic Nutritional Index (PNI) in Early Diagnosis of Gastric Cancer. J Inflamm Res 2025; 18:813-826. [PMID: 39845022 PMCID: PMC11752871 DOI: 10.2147/jir.s496703] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2024] [Accepted: 01/07/2025] [Indexed: 01/24/2025] Open
Abstract
Objective Gastric cancer (GC) is a common malignant tumor of the digestive tract. Accumulating studies suggest that inflammation is linked with the pathogenesis of GC. The study delves into novel hematological inflammatory markers, such as systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and prognostic nutritional index (PNI), to explore their potential applications in early diagnosis of GC. Methods From October 2020 and August 2024, 1339 GC patients admitted to our hospital were enrolled in this study. The pre-treatment SII, SIRI, and PNI was calculated from peripheral blood samples. Univariate and multivariate logistic regression analyses were utilized to verify independent risk factors for patients, and constructed the nomograms. The correlation between hematological indicators and tumor-node-metastasis (TNM) stage was assessed through Spearman's analysis. Results Eligible patients and healthy controls were grouped by gender. The diagnostic ability of PNI was significantly superior to other indicators to diagnose male GC (area under the curve [AUC]=0.908, 95% CI: 0.892-0.925) and female GC (AUC=0.890, 95% CI: 0.865-0.914). Besides, the combination of hematological indicators is more effective in diagnosing GC patients, especially for male patients (AUC=0.916, 95% CI: 0.901-0.932, sensitivity: 84.98%, specificity: 84.29%). The C-statistic of Nomogram model was 0.917 for males and 0.875 for females. In both male and female cohorts, CEA, SII, and SIRI were positively correlated with TNM stage, while PNI was negatively correlated. The AUC of CEA, SII, SIRI, and PNI combined for the diagnosis in the early stage of male GC patients was 0.897 (95% CI: 0.875-0.918, sensitivity: 86.57%, specificity: 80.30%) is higher than that of in the advanced stage (AUC: 0.745, 95% CI: 0.710-0.780, sensitivity: 56.53%, specificity: 82.86%). Conclusion The combined CEA, SII, PNI, and SIRI could be used as screening biomarkers in diagnosing GC, especially in the early stage of male GC patients.
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Affiliation(s)
- Junyu Zheng
- Department of Clinical Laboratory, Jiangsu Cancer Hospital & Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, People’s Republic of China
| | - Lijun Zheng
- Department of Clinical Laboratory, Nanjing Lishui District Hospital of Traditional Chinese Medicine, Nanjing, People’s Republic of China
| | - Xiao Wang
- Department of CT, Jiangsu Cancer Hospital & Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, People’s Republic of China
| | - Xuelian Mao
- Department of Clinical Laboratory, Jiangsu Cancer Hospital & Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, People’s Republic of China
| | - Qin Wang
- Department of Clinical Laboratory, Jiangsu Cancer Hospital & Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, People’s Republic of China
| | - Yining Yang
- Department of Clinical Laboratory, Jiangsu Cancer Hospital & Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, People’s Republic of China
| | - Dongping Mo
- Department of Clinical Laboratory, Jiangsu Cancer Hospital & Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, People’s Republic of China
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Cao M, Hu C, Li F, He J, Li E, Zhang R, Shi W, Zhang Y, Zhang Y, Yang Q, Zhao Q, Shi L, Xu Z, Cheng X. Development and validation of a deep learning model for predicting gastric cancer recurrence based on CT imaging: a multicenter study. Int J Surg 2024; 110:7598-7606. [PMID: 38896865 PMCID: PMC11634148 DOI: 10.1097/js9.0000000000001627] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Accepted: 05/06/2024] [Indexed: 06/21/2024]
Abstract
INTRODUCTION The postoperative recurrence of gastric cancer (GC) has a significant impact on the overall prognosis of patients. Therefore, accurately predicting the postoperative recurrence of GC is crucial. METHODS This retrospective study gathered data from 2813 GC patients who underwent radical surgery between 2011 and 2017 at two medical centers. Follow-up was extended until May 2023, and cases were categorized as recurrent or nonrecurrent based on postoperative outcomes. Clinical pathological information and imaging data were collected for all patients. A new deep learning signature (DLS) was generated using pretreatment computed tomography images, based on a pretrained baseline (a customized Resnet50), for predicting postoperative recurrence. The deep learning fusion signature (DLFS) was created by combining the score of DLS with the weighted values of identified clinical features. The predictive performance of the model was evaluated based on discrimination, calibration, and clinical usefulness. Survival curves were plotted to investigate the differences between DLFS and prognosis. RESULTS In this study, 2813 patients with GC were recruited and allocated into training, internal validation, and external validation cohorts. The DLFS was developed and assessed for its capability in predicting the risk of postoperative recurrence. The DLFS exhibited excellent performance with AUCs of 0.833 (95% CI: 0.809-0.858) in the training set, 0.831 (95% CI: 0.792-0.871) in the internal validation set, and 0.859 (95% CI: 0.806-0.912) in the external validation set, along with satisfactory calibration across all cohorts ( P >0.05). Furthermore, the DLFS model significantly outperformed both the clinical model and DLS ( P <0.05). High-risk recurrent patients exhibit a significantly poorer prognosis compared to low-risk recurrent patients ( P <0.05). CONCLUSIONS The integrated model developed in this study, focusing on GC patients undergoing radical surgery, accurately identifies cases at high-risk of postoperative recurrence and highlights the potential of DLFS as a prognostic factor for GC patients.
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Affiliation(s)
- Mengxuan Cao
- Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang
- Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou
| | - Can Hu
- Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang
- Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou
| | - Feng Li
- School of Biomedical Engineering, ShanghaiTech University, Shanghai
| | - Jingyang He
- Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang
- Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou
| | - Enze Li
- Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang
- Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou
| | - Ruolan Zhang
- Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang
- Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou
| | - Wenyi Shi
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou
- School of Molecular Medicine, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou
| | - Yanqiang Zhang
- Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang
- Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou
| | - Yu Zhang
- Zhejiang Hospital of Traditional Chinese Medicine, Hangzhou, Zhejiang, People’s Republic of China
| | - Qing Yang
- Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang
- Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou
| | - Qianyu Zhao
- Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang
- Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou
| | - Lei Shi
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou
- Department of Radiology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou
| | - Zhiyuan Xu
- Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang
- Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou
| | - Xiangdong Cheng
- Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang
- Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou
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Wong HJ, Rawal R, Tseng J, Phillips E, Gangi A, Burch M. Enhancing Lymph Node Yield in Gastric Cancer Resection: Impact of Back Table Dissection on Number of Lymph Node Examined. Am Surg 2024; 90:2622-2627. [PMID: 38709236 DOI: 10.1177/00031348241250038] [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] [Indexed: 05/07/2024]
Abstract
INTRODUCTION During gastric cancer resection, back table dissection (BTD) involves examination and separation of lymph node (LN) packets from the surgical specimen based on LN stations, which are sent to pathology as separately labeled specimens. With potential impact on clinical outcomes, we aimed to explore how BTD affects number of LNs examined. METHODS A retrospective review of a gastric cancer database was performed, including all cases of gastrectomy with D2 lymphadenectomy from January 2009 to March 2022. Back table dissection and conventional groups were compared using Mann-Whitney U and Fisher's exact tests. Multiple linear regression modeling was used to identify potential predictors of number of LN examined. RESULTS A total of 174 patients were identified: 39 (22%) BTD and 135 (78%) conventional. More patients in the BTD group underwent neoadjuvant chemotherapy (62% vs 29%, P < .05). Compared to the conventional group, the BTD group had a greater number of LNs examined (42 [26-59] vs 21[15-33], median [IQR], P < .001), lower LN positivity ratio (.01 vs .07, P = .013), and greater number of LNs in patients with BMI >35 (32.5[27.5-39] vs 22[13-27], P = .041). A multiple linear regression model controlling for age, BMI, preoperative N stage, neoadjuvant chemotherapy, surgeon experience, and operative approach identified BTD as a significant positive predictor of number of LN examined (β = 19.7, P = .001). CONCLUSION Back table dissection resulted in improved LN yield during gastric cancer resection. As a simple technical addition, BTD helps enhance pathology examination and improve surgeon awareness, which may ultimately translate to improve oncologic outcomes.
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Affiliation(s)
- Harry J Wong
- Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Rushil Rawal
- Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Joshua Tseng
- Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Edward Phillips
- Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Alexandra Gangi
- Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Miguel Burch
- Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA
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Li X, Zhang J, Fu Z. Development and Validation of an Inflammation-Combined Prognostic Index (ICPI)-Based Nomogram for Predicting Overall Survival in Gastric Cancer. J Inflamm Res 2024; 17:5439-5452. [PMID: 39165321 PMCID: PMC11334928 DOI: 10.2147/jir.s476346] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2024] [Accepted: 08/07/2024] [Indexed: 08/22/2024] Open
Abstract
Purpose This study aims to investigate the correlation between a novel integrated inflammatory marker: The inflammation-combined prognostic index (ICPI), combining NLR, PLR, and MLR, with the clinicopathological characteristics and overall survival (OS) of gastric cancer (GC). Patients and Methods Data from 876 patients with GC were retrospectively analyzed from January 1, 2017, to April 30, 2023. PSM was employed to mitigate confounding factors between groups. Receiver operating characteristic (ROC) curves were utilized to determine the optimal cutoff value. Univariate, LASSO, and multivariate regression analyses were executed. Subsequently, a nomogram for predicting OS was developed and validated. Results The cohort with a poor prognosis exhibited significantly elevated levels of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and ICPI (P<0.001). Similarly, higher levels of NLR, PLR, MLR, and ICPI were associated with a poorer prognosis (P<0.001). Following regression analysis, ICPI, T-stage, lymph node ratio (LNR), and primary site were identified as independent risk factors affecting OS. A nomogram was constructed based on these factors to predict 1-, 3-, and 5-year OS, yielding C-indexes of 0.8 and 0.743 for the training and validation sets, respectively. The calibration curves demonstrated close alignment between predicted and actual results, indicating high predictive accuracy. Moreover, the decision curve underscored the practical utility of the model. Conclusion The new inflammatory parameter ICPI integrates NLR, PLR and MLR. The ICPI-based nomogram and web calculator accurately predict OS in patients with GC.
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Affiliation(s)
- Xiang Li
- Department of General Surgery, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China
- Department of General Surgery, Chongqing University FuLing Hospital, Chongqing, People’s Republic of China
| | - Jun Zhang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China
| | - Zhongxue Fu
- Department of General Surgery, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China
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Karra S, Sinduja R, Gurushankari B, Elamurugan TP, Mahalakshmy T, Kate V, Nanda N, Rajesh NG, Rajeswari M, Raj R, Shankar G. Development of Panel of Three-Dimensional Biomarkers to Identify Gastric Carcinoma and Precancerous Lesions of the Stomach - An Analytical Cross-Sectional Study. Indian J Clin Biochem 2024. [DOI: 10.1007/s12291-024-01257-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Accepted: 07/31/2024] [Indexed: 01/04/2025]
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10
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Han YL, Chen L, Wang XN, Xu ML, Qin R, Gong FM, Sun P, Liu HY, Teng ZP, Li ZX, Dai GH. Association of tumour mutation burden with prognosis and its clinical significance in stage III gastric cancer. BIOIMPACTS : BI 2024; 14:30118. [PMID: 39493897 PMCID: PMC11530966 DOI: 10.34172/bi.2024.30118] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/15/2023] [Revised: 12/11/2023] [Accepted: 12/12/2023] [Indexed: 11/05/2024]
Abstract
Introduction To explore the correlation between the tumour mutation burden (TMB) and prognosis and its clinical significance among patients with stage III gastric cancer (GC). Methods Patients with stage III GC were divided into a high TMB and low TMB group in both a study cohort of 38 patients and the Cancer Genome Atlas (TCGA) cohort of 173 patients. In the study cohort, next-generation sequencing was used to detect mutated GC genes and obtain TMB data. In the TCGA cohort, gene set enrichment analysis was performed, and the relationship between TMB, prognosis and clinicopathologic factors was analysed. Western blot and quantitative real-time polymerase chain reaction were used to detect the expression levels of both proteins and genes. Cell viability was measured using methyl thiazolyl tetrazolium and transwell cell assays. Results Patients in the high TMB group had better overall survival (OS) rates than patients in the low TMB group for both cohorts and TMB was associated with age, mutation signature 1 and mutation signature 17. The Cox regression analysis revealed that age, not TMB, was an independent prognosis factor. Furthermore, genes with high-frequency mutations were significantly enriched in the RTK-RAS and Notch signalling pathways. The activation of these pathways was lower in the high TMB compared with the low TMB group, and the proliferation and migration abilities of GC cells showed a similar pattern in both TMB groups. Conclusion Patients in the high TMB group had better OS rates than patients in the low TMB group. Genes with high-frequency mutations were significantly enriched in the RTK-RAS and Notch pathways. Hence, TMB could serve as a prognosis biomarker with potential clinical significance.
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Affiliation(s)
- Ya-Lin Han
- Department of General Surgery, The First Medical Centre, Chinese PLA General Hospital, Beijing 100853, China
- Department of Oncology, PLA Rocket Force Characteristic Medical Centre, Beijing 100088, China
| | - Li Chen
- Department of Oncology, Fifth Medical Center of Chinese PLA General Hospital, Beijing 100071, China
| | - Xu-Ning Wang
- Department of General Surgery, The Air Force Hospital of Northern Theater PLA, Shenyang 110042, China
| | - Mao-Lin Xu
- Department of General Surgery, The First Medical Centre, Chinese PLA General Hospital, Beijing 100853, China
| | - Rui Qin
- Department of Gastroenterology, The 305 Hospital of PLA, Beijing 100017, China
| | - Fang-Ming Gong
- Department of General Surgery, The First Medical Centre, Chinese PLA General Hospital, Beijing 100853, China
| | - Peng Sun
- Department of General Surgery, The First Medical Centre, Chinese PLA General Hospital, Beijing 100853, China
| | - Hong-Yi Liu
- Department of General Surgery, The First Medical Centre, Chinese PLA General Hospital, Beijing 100853, China
| | - Zhi-Peng Teng
- Department of General Surgery, The First Medical Centre, Chinese PLA General Hospital, Beijing 100853, China
| | - Zhao-Xia Li
- Department of Oncology, PLA Rocket Force Characteristic Medical Centre, Beijing 100088, China
| | - Guang-Hai Dai
- Department of Oncology, Fifth Medical Center of Chinese PLA General Hospital, Beijing 100071, China
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11
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You Y, Wang Y, Yu X, Gao F, Li M, Li Y, Wang X, Jia L, Shi G, Yang L. Prediction of lymph node metastasis in advanced gastric adenocarcinoma based on dual-energy CT radiomics: focus on the features of lymph nodes with a short axis diameter ≥6 mm. Front Oncol 2024; 14:1369051. [PMID: 38496754 PMCID: PMC10940341 DOI: 10.3389/fonc.2024.1369051] [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: 01/11/2024] [Accepted: 02/15/2024] [Indexed: 03/19/2024] Open
Abstract
Objective To explore the value of the features of lymph nodes (LNs) with a short-axis diameter ≥6 mm in predicting lymph node metastasis (LNM) in advanced gastric adenocarcinoma (GAC) based on dual-energy CT (DECT) radiomics. Materials and methods Data of patients with GAC who underwent radical gastrectomy and LN dissection were retrospectively analyzed. To ensure the correspondence between imaging and pathology, metastatic LNs were only selected from patients with pN3, nonmetastatic LNs were selected from patients with pN0, and the short-axis diameters of the enrolled LNs were all ≥6 mm. The traditional features of LNs were recorded, including short-axis diameter, long-axis diameter, long-to-short-axis ratio, position, shape, density, edge, and the degree of enhancement; univariate and multivariate logistic regression analyses were used to establish a clinical model. Radiomics features at the maximum level of LNs were extracted in venous phase equivalent 120 kV linear fusion images and iodine maps. Intraclass correlation coefficients and the Boruta algorithm were used to screen significant features, and random forest was used to build a radiomics model. To construct a combined model, we included the traditional features with statistical significance in univariate analysis and radiomics scores (Rad-score) in multivariate logistic regression analysis. Receiver operating curve (ROC) curves and the DeLong test were used to evaluate and compare the diagnostic performance of the models. Decision curve analysis (DCA) was used to evaluate the clinical benefits of the models. Results This study included 114 metastatic LNs from 36 pN3 cases and 65 nonmetastatic LNs from 28 pN0 cases. The samples were divided into a training set (n=125) and a validation set (n=54) at a ratio of 7:3. Long-axis diameter and LN shape were independent predictors of LNM and were used to establish the clinical model; 27 screened radiomics features were used to build the radiomics model. LN shape and Rad-score were independent predictors of LNM and were used to construct the combined model. Both the radiomics model (area under the curve [AUC] of 0.986 and 0.984) and the combined model (AUC of 0.970 and 0.977) outperformed the clinical model (AUC of 0.772 and 0.820) in predicting LNM in both the training and validation sets. DCA showed superior clinical benefits from radiomics and combined models. Conclusion The models based on DECT LN radiomics features or combined traditional features have high diagnostic performance in determining the nature of each LN with a short-axis diameter of ≥6 mm in advanced GAC.
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Affiliation(s)
- Yang You
- Department of Computed Tomography and Magnetic Resonance, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Yan Wang
- Department of Computed Tomography and Magnetic Resonance, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Xianbo Yu
- CT Collaboration, Siemens Healthineers Ltd., Beijing, China
| | - Fengxiao Gao
- Department of Computed Tomography and Magnetic Resonance, Xing Tai People’s Hospital, Xingtai, China
| | - Min Li
- Department of Computed Tomography and Magnetic Resonance, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Yang Li
- Department of Computed Tomography and Magnetic Resonance, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Xiangming Wang
- Department of Computed Tomography and Magnetic Resonance, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Litao Jia
- Department of Computed Tomography and Magnetic Resonance, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Gaofeng Shi
- Department of Computed Tomography and Magnetic Resonance, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Li Yang
- Department of Computed Tomography and Magnetic Resonance, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
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12
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Cao M, Hu C, Pan S, Zhang Y, Yu P, Zhang R, Cheng X, Xu Z. Development and validation of nomogram for predicting early recurrence after radical gastrectomy of gastric cancer. World J Surg Oncol 2024; 22:21. [PMID: 38243254 PMCID: PMC10797937 DOI: 10.1186/s12957-023-03294-1] [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: 08/22/2023] [Accepted: 12/26/2023] [Indexed: 01/21/2024] Open
Abstract
BACKGROUND After radical surgery, early detection of recurrence and metastasis is a crucial factor in enhancing the prognosis and survival of patients with gastric cancer (GC). Therefore, assessing the risk of recurrence in gastric cancer patients and determining the timing for postoperative recurrence is crucial. METHODS The clinicopathological data of 521 patients with recurrent gastric cancer, who underwent radical gastrectomy at Zhejiang Cancer Hospital between January 2010 and January 2017, were retrospectively analyzed. These patients were randomly divided into two groups: a training group (n = 365) and a validation group (n = 156). In the training set, patients were further categorized into early recurrence (n = 263) and late recurrence (n = 102) groups based on a 2-year boundary. Comparative analyses of clinicopathological features and prognoses were conducted between these two groups. Subsequently, a nomogram for predicting early recurrence was developed and validated. RESULTS In this study, the developed nomogram incorporated age, serous infiltration, lymph node metastasis, recurrence mode, and the tumour marker CA19-9. In the training cohort, the area under the curve (AUC value) was 0.739 (95% CI, 0.682-0.798), with a corresponding C-index of 0.739. This nomogram was subsequently validated in an independent validation cohort, yielding an AUC of 0.743 (95% CI, 0.652-0.833) and a C-index of 0.743. Furthermore, independent risk factors for prognosis were identified, including age, absence of postoperative chemotherapy, early recurrence, lymph node metastasis, abdominal metastasis, and vascular cancer embolus. CONCLUSION Independent risk factors for gastric cancer recurrence following radical surgery were utilized to construct a nomogram for predicting early relapse. This nomogram effectively assesses the risk of recurrence, aids in treatment decision-making and follow-up planning in clinical settings, and demonstrated strong performance in the validation cohort.
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Affiliation(s)
- Mengxuan Cao
- Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, China
- Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, 310018, China
- Wenzhou Medical University, Wenzhou, 325035, China
| | - Can Hu
- Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, China
- Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, 310018, China
| | - Siwei Pan
- Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, China
- Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, 310018, China
| | - Yanqiang Zhang
- Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, China
- Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, 310018, China
| | - Pengcheng Yu
- Department of Colorectal Surgery, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, 321000, China
| | - Ruolan Zhang
- Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, China
- Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, 310018, China
| | - Xiangdong Cheng
- Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, China.
- Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, 310018, China.
| | - Zhiyuan Xu
- Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, China.
- Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, 310018, China.
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Zhang J, Li K, Zhang Z, Zhang G, Zhang S, Zhao Y, Gao Z, Ma H, Xie Y, Han J, Zhang L, Zhang B, Liu Y, Wu T, Wu Y, Xiao Y, Wang X. Short-and long-term outcomes of one-stage versus two-stage gastrectomy for perforated gastric cancer: a multicenter retrospective propensity score-matched study. World J Surg Oncol 2024; 22:7. [PMID: 38172888 PMCID: PMC10763372 DOI: 10.1186/s12957-023-03283-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Accepted: 12/09/2023] [Indexed: 01/05/2024] Open
Abstract
OBJECTIVE There is no scientific consensus about the treatment of perforated gastric cancer (PGC). Therefore, the aim of this study was to investigate which is the better treatment option for PGC between the single-stage and two-stage strategies. METHODS All 81 PGC patients from 13 medical institutions were retrospectively enrolled in this study. The PGC patients who underwent R0 gastrectomy were divided into one-stage surgery and two-stage surgery groups. The clinicopathological characteristics of the two groups were compared, and 415 regular gastric cancer patients without perforation were randomly selected as a control. The propensity score matching (PSM) method was used to find matched regular GC patients with similar clinicopathological parameters. The OS (overall survival) and the number harvested lymph nodes from PGC patients and regular GC patients were compared. RESULTS Compared with PGC patients who underwent one-stage surgery, those who underwent two-stage surgery harvested significantly more lymph nodes [31(27, 38) vs 17 (12, 24), P < 0.001], required less blood transfusion [0 (0, 100) vs 200 (0, 800), P = 0.034], had a shorter ICU stay [0 (0, 1.5) vs 3 (0, 3), P = 0.009], and had a significantly better OS (Median OS: 45 months vs 11 months, P = 0.007). Compared with propensity score-matched regular GC patients without perforation, PGC patients who underwent one-stage gastrectomy had a poorer quality of lymphadenectomy [17 (12, 24) vs 29 (21, 37), P < 0.001] and suffered a worse OS (Median OS: 18 months vs 30 months, P = 0.024). Conversely, two-stage gastrectomy can achieve a comparable quality of lymphadenectomy (P = 0.506) and a similar OS (P = 0.096) compared to propensity score-matched regular GC patients. CONCLUSIONS For PGC patients in poor condition, two-stage treatment is a better option when D2 radical gastrectomy cannot be achieved in emergency surgery, based on our findings that two-stage gastrectomy could provide PGC patients with a better quality of lymphadenectomy and a better OS.
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Affiliation(s)
- Junling Zhang
- Department of Gastrointestinal Surgery, Peking University First Hospital, No.8, Xishiku Street, Xicheng District, Beijing, 100034, P. R. China
| | - Kexuan Li
- Division of Colorectal Surgery, Department of General Surgery, Peking Union Medical College Hospital, No.1 Shuaifuyuan Wangfujing Street, Dongcheng District, Beijing, 100730, P. R. China
| | - Zongnai Zhang
- Department of General Surgery, Civil Aviation General Hospital, No.1A, Gaojing, Chaoyangmenwai Avenue, Chaoyang District, Beijing, 100123, P. R. China
| | - Guochao Zhang
- Department of General Surgery, China-Japan Friendship Hospital, East Yinghuayuan Street, Chaoyang District, Beijing, 100029, P. R. China
| | - Shupeng Zhang
- Department of General Surgery, Tianjin Fifth Central Hospital, No.41 Zhejiang Road, Binhai New Area, Tianjin, 300450, P. R. China
| | - Yinming Zhao
- Department of General Surgery, Beijing Jingmei Group General Hospital, No.18, Heishan Street, Mentougou District, Beijing, 102399, P. R. China
| | - Zhaoya Gao
- Department of General Surgery, Peking University Shougang Hospital, No.9, Jinyuanzhuang Road, Shijingshan District, Beijing, 100144, P. R. China
| | - Haiyun Ma
- Department of General Surgery, Beijing Miyun District Hospital, Miyun District, No.36 Mixi Road, Beijing, 101500, P. R. China
| | - Yong Xie
- Department of General Surgery, Hebei General Hospital, No.348 Heping West Road, Xinhua District, Shijiazhuang, Hebei Province, 050051, P. R. China
| | - Jinsheng Han
- Department of General Surgery, Cangzhou Integrated Traditional Chinese and Western Medicine Hospital, No.31 Huanghe West Road, Yunhe District, Cangzhou, Hebei Province, 061011, P. R. China
| | - Li Zhang
- Department of General Surgery, First Hospital of Qinhuangdao, No. 258 Wenhua Road, Haigang District, Qinhuangdao, Hebei Province, 066000, P. R. China
| | - Baoliang Zhang
- Department of General Surgery, Tangshan Workers' Hospital, No.27, Wenhua Road, Tangshan, Hebei Province, 063003, P. R. China
| | - Yang Liu
- Department of General Surgery, North China University of Science and Technology Affiliated Hospital, No.73 Jianshe South Road, Lubei District, Tangshan, Hebei Province, 063000, P. R. China
| | - Tao Wu
- Department of Gastrointestinal Surgery, Peking University First Hospital, No.8, Xishiku Street, Xicheng District, Beijing, 100034, P. R. China
| | - Yingchao Wu
- Department of Gastrointestinal Surgery, Peking University First Hospital, No.8, Xishiku Street, Xicheng District, Beijing, 100034, P. R. China.
| | - Yi Xiao
- Division of Colorectal Surgery, Department of General Surgery, Peking Union Medical College Hospital, No.1 Shuaifuyuan Wangfujing Street, Dongcheng District, Beijing, 100730, P. R. China.
| | - Xin Wang
- Department of Gastrointestinal Surgery, Peking University First Hospital, No.8, Xishiku Street, Xicheng District, Beijing, 100034, P. R. China.
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14
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Xue D, Peng H, Li Z, Xu J, Ma H, Dang Y, Li F, Wang G, Sun Q. Comprehensive analysis reveals TSPEAR as a prognostic biomarker in colorectal cancer. J Cancer 2024; 15:809-824. [PMID: 38213725 PMCID: PMC10777046 DOI: 10.7150/jca.90028] [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: 09/11/2023] [Accepted: 11/27/2023] [Indexed: 01/13/2024] Open
Abstract
Background: Colorectal cancer (CRC) is one of the most common malignant tumors and has high morbidity and mortality rates. Previous studies have shown that TSPEAR mutations are involved in the development and progression of gastric cancer and liver cancer. However, the role of TSPEAR in CRC is still unclear. Methods: In The Cancer Genome Atlas (TCGA) database, 590 CRC patients with complete survival information were analyzed. We assessed TSPEAR expression in a pan-cancer dataset from the TCGA database. Cox regression analysis was performed to evaluate factors associated with prognosis. Enrichment analysis via the R package "clusterProfiler" was used to explore the potential function of TSPEAR. The single-sample GSEA (ssGSEA) method from the R package "GSVA" and the TIMER database were used to investigate the association between the immune infiltration level and TSPEAR expression in CRC. The R package "maftools" was used to explore the association between tumour mutation burden (TMB) and TSPEAR expression in CRC. CCK-8 assays and cell invasion assays were used to detect the effect of TSPEAR and TGIF2 on the biological behavior of CRC cells. Results: Pan-cancer analysis revealed that TSPEAR was upregulated in CRC tissues compared to normal tissues and that high TSPEAR expression was associated with poorer overall survival (OS) (p=0.0053). The expression of TSPEAR increased with increasing TNM stage, T stage, N stage, and M stage. The nomogram constructed with TSPEAR, age, and TNM stage showed better predictive value than TSPEAR, age, or TNM stage alone. Immune cell infiltration analysis revealed that high expression of TSPEAR was associated with lower immune cell infiltration. Tumor mutation burden (TMB) analysis indicated that high expression of TSPEAR was associated with lower TMB (p=0.005), and high TMB was associated with shorter OS (p=0.02). CCK-8 assays and cell invasion assays indicated that in vitro knockdown of TSPEAR inhibited the proliferation, migration, and invasion of CRC cells. In addition, TSPEAR expression may be regulated by the upstream transcription factor TGIF2. Conclusion: TSPEAR expression was higher in CRC tissues than in normal tissues. Its upregulation was significantly associated with a poor prognosis. Additionally, TSPEAR plays a significant role in tumor immunity and the biological behavior of CRC cells. Thus, TSPEAR may become a promising prognostic biomarker and therapeutic target for CRC patients.
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Affiliation(s)
- Dong Xue
- Department of General Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Hang Peng
- Department of Talent Highland, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Zhenghui Li
- Department of General Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Jiarui Xu
- Department of General Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Haiyun Ma
- Department of General Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Yueyan Dang
- Department of General Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Fanni Li
- Department of Talent Highland, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Guanghui Wang
- Department of General Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Qi Sun
- Department of General Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
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15
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Karra S, Gurushankari B, Rajalekshmy MR, Elamurugan TP, Mahalakshmy T, Kate V, Nanda N, Rajesh NG, Shankar G. Diagnostic Utility of NLR, PLR and MLR in Early Diagnosis of Gastric Cancer: an Analytical Cross-Sectional Study. J Gastrointest Cancer 2023; 54:1322-1330. [PMID: 37198382 DOI: 10.1007/s12029-023-00937-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/15/2023] [Indexed: 05/19/2023]
Abstract
PURPOSE Inflammatory markers such as neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and monocyte-to-lymphocyte ratio (MLR) are linked with the pathogenesis of gastric cancer (GC). However, the clinical significance of the combination of these markers is unclear. Hence, this study was carried out to determine the individual and combined diagnostic accuracy of NLR, PLR and MLR among patients with GC. METHODS In this prospective, cross-sectional study, patients were recruited into three groups, GC, precancerous lesions and age and gender-matched controls. The primary outcome was to determine the diagnostic accuracy of inflammatory markers in the diagnosis of GC. The secondary outcome was to determine the correlation of inflammatory markers with the stage of gastric cancer, nodal involvement and metastasis. RESULTS A total of 228 patients, 76 in each group, were enrolled. The cut-off value of NLR, PLR and MLR were 2.23, 146.8 and 0.26, respectively, for the diagnosis of GC. The diagnostic abilities of NLR, PLR and MLR were significantly high at 79, 75 and 68.4, respectively, to predict GC compared to precancerous and control groups. All the models of inflammatory markers showed excellent discrimination between GC and the controls with an AUC > 0.7. The models also showed acceptable discrimination between GC and the precancerous lesion group with AUC between 0.65 and 0.70. No significant difference was found in correlating inflammatory markers with clinicopathological features. CONCLUSION The discrimination capacity of the inflammatory markers could be used as screening biomarkers in diagnosing GC, even in its early stages.
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Affiliation(s)
- Sandhya Karra
- Department of Surgery, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, 605006, India
| | | | - Mini Rajesh Rajalekshmy
- Department of Surgery, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, 605006, India
| | - T P Elamurugan
- Department of Surgery, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, 605006, India
| | - T Mahalakshmy
- Department of Preventive & Social Medicine, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, India
| | - Vikram Kate
- Department of Surgery, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, 605006, India.
| | - Nivedita Nanda
- Department of Biochemistry, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, India
| | - Nachiappa Ganesh Rajesh
- Department of Pathology, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, India
| | - Gomathi Shankar
- Department of Surgery, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, 605006, India
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16
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An S, Eo W, Lee S. Prognostic significance of a five-factor modified frailty index in patients with gastric cancer undergoing curative-intent resection: A cohort study. Medicine (Baltimore) 2023; 102:e36065. [PMID: 37986354 PMCID: PMC10659737 DOI: 10.1097/md.0000000000036065] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2023] [Revised: 09/16/2023] [Accepted: 10/20/2023] [Indexed: 11/22/2023] Open
Abstract
The 5-factor modified frailty index (mFI-5) evaluates frailty based on variables including functional status, diabetes, chronic obstructive pulmonary disease, congestive heart failure, and hypertension requiring medication. Despite its effectiveness in predicting surgical risk, the potential of mFI-5 as a predictor of long-term survival in patients with gastric cancer (GC) has not been investigated. This study aims to assess the prognostic significance of mFI-5 in patients with GC who have undergone curative-intent gastric resection. Among the 494 patients diagnosed with stage I to III GC, multivariate analysis revealed that age, tumor-node-metastasis (TNM) stage, geriatric nutritional risk index, mFI-5, and the type of gastrectomy were significant predictors for both overall survival (OS) and disease-free survival (DFS). We assessed 3 models: Baseline model (BM, TNM stage only), interim model (IM, all significant variables except mFI-5), and full model (FM, all significant variables including mFI-5). FM outperformed BM for OS (C-index 0.818 vs 0.683; P < .001) and DFS (C-index 0.805 vs 0.687; P < .001). Similarly, IM outperformed BM for OS (C-index 0.811 vs 0.683; P < .001) and DFS (C-index 0.797 vs 0.687; P < .001). Multiple metrics consistently supported the improved discriminative capacity of FM and IM compared to BM. However, while FM exhibits enhanced predictive capacity over IM, this improvement lacks statistical significance across key metrics. In conclusion, our study highlights the clinical significance of the mFI-5, along with age, TNM stage, geriatric nutritional risk index, and type of gastrectomy, as valuable predictors of long-term survival in GC patients. The FM consistently demonstrates enhanced predictive accuracy compared to the BM. However, it is important to note that while the FM improves predictive power over the IM, this enhancement does not achieve statistical significance across multiple metrics. These findings collectively emphasize the potential clinical value of the FM as a robust tool for surgeons in predicting long-term survival outcomes before surgery in patients with GC.
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Affiliation(s)
- Soomin An
- Department of Nursing, Dongyang University, Gyeongbuk, Republic of Korea
| | - Wankyu Eo
- Department of Internal Medicine, College of Medicine, Kyung Hee University, Seoul, Republic of Korea
| | - Sookyung Lee
- Department of Clinical Oncology, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea
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Liu S, Xu K, Min J, Hou W, Zhang L, Lei J. Effect of transarterial chemotherapy on the outcome and prognosis of patients with locally advanced proximal gastric cancer. Am J Transl Res 2023; 15:1309-1317. [PMID: 36915756 PMCID: PMC10006749] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2022] [Accepted: 01/06/2023] [Indexed: 03/16/2023]
Abstract
OBJECTIVE To investigate the effect of transarterial infusion chemotherapy on the prognosis of patients undergoing proximal radical gastrectomy for gastric cancer. METHODS In this retrospective study, 96 patients with locally advanced proximal gastric cancer diagnosed in Gansu Cancer Hospital from July 2014 to July 2017 were enrolled. Among them, 40 patients undergoing surgery after 4 cycles of intravenous + oral chemotherapy and 2-4 cycles of adjuvant chemotherapy after surgery were grouped as the control group (CG); the remaining 56 patients treated with left gastric artery infusion chemotherapy were grouped as the observation group (OG). The clinical efficacy, surgical regimen, adverse reactions (nausea, vomiting, and bone marrow suppression) after chemotherapy, improvement of clinical symptoms, 5-year survival, 5-year progression-free survival (PFS) and overall response rate (ORR) after treatment were compared between the two groups. Cox regression was used to analyze prognostic factors affecting PFS. RESULTS Compared to the CG, the OG exhibited a significantly higher overall response rate and smaller tumor volume (P < 0.05 or P < 0.01); the overall incidence of clinical symptoms in the OG was lower (P < 0.05); the proportion of patients who underwent radical resection in the OG was significantly higher (P < 0.05); nausea and vomiting symptoms were more common in the OG (P < 0.05), but there was no statistical difference in terms of bone marrow suppression (P > 0.05); and the OG had significantly higher 5-year progression-free survival and survival time of patients (P < 0.05). Cox regression analysis revealed that tumor stage, tumor type and treatment regimen were independent prognostic factors for PFS (P < 0.01). CONCLUSION Regional arterial infusion chemotherapy is an ideal neoadjuvant therapy for gastric cancer, which can evidently reduce the tumor lesions in a short time, increase the resection rate, and significantly prolong the PFS of the patients. The gastrointestinal side effects are comparatively significant but tolerable.
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Affiliation(s)
- Shuwen Liu
- The First Department of Abdominal Surgery, Gansu Provincial Tumor Hospital Lanzhou 730050, Gansu, China
| | - Kerui Xu
- The First Department of Abdominal Surgery, Gansu Provincial Tumor Hospital Lanzhou 730050, Gansu, China
| | - Jianping Min
- Department of Translational Medicine, Gansu Provincial Tumor Hospital Lanzhou 730050, Gansu, China
| | - Wenpei Hou
- The Second Department of Gastroenterology and Oncology Medicine, Gansu Provincial Tumor Hospital Lanzhou 730050, Gansu, China
| | - Lianxing Zhang
- The Second Department of Gastroenterology and Oncology Medicine, Gansu Provincial Tumor Hospital Lanzhou 730050, Gansu, China
| | - Jieqiong Lei
- Interventional Therapy Department, Gansu Provincial Tumor Hospital Lanzhou 730050, Gansu, China
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Lee KH, Kim SJ, Woo JS, Lee SY, Jhun J, Moon J, Jung YJ, Cho ML, Song KY. Prognostic significances of PD-L1- and CTLA-4-positive T cells and positive correlations of immunosuppressive marker expression between cancer tissue and peripheral blood in patients with gastric cancer. Front Immunol 2023; 14:1138743. [PMID: 37153541 PMCID: PMC10160473 DOI: 10.3389/fimmu.2023.1138743] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2023] [Accepted: 04/11/2023] [Indexed: 05/09/2023] Open
Abstract
Introduction Although tumor, node, metastasis (TNM) staging has been used for prognostic assessment of gastric cancer (GC), the prognosis may vary among patients with the same TNM stage. Recently, the TNM-Immune (TNM-I) classification staging system has been used for prognostic assessment of colorectal cancer based on intra-tumor T-cell status, which is a superior prognostic factor compared with the American Joint Committee on Cancer staging manual. However, an immunoscoring system with prognostic significance for GC has not been established. Method Here, we evaluated immune phenotypes in cancer and normal tissues, then examined correlations between tissues and peripheral blood. GC patients who underwent gastrectomy at Seoul St. Mary's Hospital between February 2000 and May 2021 were included. We collected 43 peripheral blood samples preoperatively and a pair of gastric mucosal samples postoperatively, including normal and cancer mucosa, which did not influence tumor diagnosis and staging. Tissue microarray samples of GC were collected from 136 patients during surgery. We investigated correlations of immune phenotypes between tissues and peripheral blood using immunofluorescence imaging and flow cytometry, respectively. GC mucosa exhibited an increased number of CD4+ T cells, as well as increased expression levels of immunosuppressive markers (e.g., programmed death-ligand-1 [PD-L1], cytotoxic T lymphocyte antigen-4 [CTLA-4], and interleukin-10), in CD4+ T cells and non-T cells. Result The expression levels of immunosuppressive markers were significantly increased in cancer tissues and peripheral blood mononuclear cells. In gastric mucosal tissues and peripheral blood of GC patients, similar immunosuppression phenotypes were observed, including increased numbers of PD-L1- and CTLA-4-positive T cells. Discussion Therefore, peripheral blood analysis may be an important tool for prognostic assessment of GC patients.
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Affiliation(s)
- Kun Hee Lee
- Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Lab of Translational ImmunoMedicine, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Department of Biomedicine and Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - So Jung Kim
- Division of Gastrointestinal Surgery, Department of Surgery, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jin Seok Woo
- Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Lab of Translational ImmunoMedicine, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Seung Yoon Lee
- Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Lab of Translational ImmunoMedicine, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Department of Biomedicine and Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jooyeon Jhun
- Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Lab of Translational ImmunoMedicine, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Department of Biomedicine and Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jeonghyeon Moon
- Departments of Neurology and Immunobiology, Yale School of Medicine, New Haven, CT, United States
| | - Yoon Ju Jung
- Division of Gastrointestinal Surgery, Department of Surgery, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Mi-La Cho
- Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Lab of Translational ImmunoMedicine, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Department of Biomedicine and Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Department of Medical Life Sciences, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- *Correspondence: Mi-La Cho, ; Kyo Young Song,
| | - Kyo Young Song
- Division of Gastrointestinal Surgery, Department of Surgery, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- *Correspondence: Mi-La Cho, ; Kyo Young Song,
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Yu C, Zhou Z, Liu B, Yao D, Huang Y, Wang P, Li Y. Pathological Nodal Staging Score for Gastric Signet Ring Cell Carcinoma: A Clinical Tool of Adequate Nodal Staging. Diagnostics (Basel) 2022; 12:diagnostics12102289. [PMID: 36291978 PMCID: PMC9600920 DOI: 10.3390/diagnostics12102289] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2022] [Revised: 09/11/2022] [Accepted: 09/20/2022] [Indexed: 11/16/2022] Open
Abstract
Background: Gastric signet ring cell carcinoma (GSRCC) is a subset of gastric cancer with distinct histological and inconsistent prognosis outcome. Currently, the association between the adequate regional lymph node and proper nodal staging in GSRCC is rarely noticed. Materials and methods: Clinical data of GSRCC were retrieved from the Surveillance, Epidemiology, and End Results database. Beta-binomial distribution model was employed for the estimation of the probability of missing nodal disease, followed by the development of a nodal staging score (NSS). Results: A total of 561 GSRCC patients were included in this study, with 193 in lymph node-negative and 368 in lymph node-positive diagnoses. As the number of examined lymph nodes increased, the probability of missing nodal disease decreased rapidly, with T stage-specific curves. The probability of missing nodal disease in T4 was lower than that in T1. NSS calculation indicated that T1 stage patients commonly had NSS > 0.8. However, with the NSS of T2−T4 to reach 0.8, the number of examined lymph node was required to be larger than 12 in T2, 17 in T3 and 27 in T4. NSS ≥ 0.75 (quantile 75%) subgroup in T2−T4 subgroups tended to have better outcome; however, without significant prognostic value. Conclusions: NSS is served as a reliable and feasible tool in adequate nodal staging of GSRCC with statistical basis and provides further evidence for clinical decision making.
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