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Hu HT, Wang P, Jiang YJ, Wang HK, Shao XX, Tian YT. Nomogram-based prognostic stratification for resectable gastric signet-ring cell carcinoma and adenocarcinoma: A retrospective cohort study. World J Gastrointest Oncol 2025; 17:106244. [DOI: 10.4251/wjgo.v17.i5.106244] [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: 02/19/2025] [Revised: 03/02/2025] [Accepted: 03/11/2025] [Indexed: 05/15/2025] Open
Abstract
BACKGROUND Gastric signet-ring cell carcinoma (GSRCC) is a more aggressive subtype of gastric cancer compared to gastric adenocarcinoma (GA), with an increasing incidence. However, the prognostic differences between these subtypes, particularly in resectable cases, remain unclear.
AIM To evaluate prognostic factors and develop a predictive model for GA and GSRCC patients undergoing curative resection.
METHODS This retrospective cohort study included patients with GA and GSRCC who underwent curative surgery at the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, from 2011 to 2018. Propensity score matching (PSM) (1:1) balanced the baseline characteristics. Prognostic factors were identified using univariate and multivariate Cox and least absolute shrinkage and selection operator (LASSO) regression analyses. Model performance was evaluated through calibration curves, decision curve analysis (DCA), and time-dependent receiver operating characteristic curves. Subgroup analysis and Kaplan-Meier survival curves were generated.
RESULTS In a cohort of 3027 patients, the GSRCC group was characterized by a significantly higher prevalence of individuals under 60 years of age, females, cases with poor differentiation, and early-stage (stage I) disease (all P < 0.001). After PSM, the baseline was balanced and 761 patients were retained in each group. Variables identified through univariate Cox regression were included in the LASSO regression analysis. Multivariate Cox regression analysis identified age, tumor differentiation, tumor size, vascular invasion, and post-treatment nodal margin staging as independent prognostic factors. Subgroup analysis indicated a notably poorer prognosis for GSRCC in patients aged 60 and above (hazard ratio = 1.36, P = 0.025). The nomogram (C-index = 0.755) exhibited greater predictive accuracy than tumor node metastasis (TNM) staging for 1-, 3-, and 5-year overall survival (all P < 0.001), and provided a higher clinical net benefit according to DCA.
CONCLUSION This study systematically compared resectable GA and GSRCC, revealing no overall survival difference. However, GSRCC demonstrated a significantly elevated mortality risk in subgroups stratified by age and tumor size. Multivariate analysis identified age, differentiation, tumor size, vascular invasion, and TNM stage as independent prognostic factors. The nomogram integrates clinicopathological features for precise risk stratification, surpassing traditional TNM staging.
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Affiliation(s)
- Hai-Tao Hu
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Peng Wang
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Yu-Juan Jiang
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Hai-Kuo Wang
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Xin-Xin Shao
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Yan-Tao Tian
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
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Han J, Wang Y, Mu H, Liu J. Synchronous neuroendocrine tumor and signet ring cell carcinoma in the stomach: a case report and review of literature. Front Med (Lausanne) 2025; 12:1561231. [PMID: 40406402 PMCID: PMC12095303 DOI: 10.3389/fmed.2025.1561231] [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: 01/15/2025] [Accepted: 04/22/2025] [Indexed: 05/26/2025] Open
Abstract
Synchronous neoplasms of the stomach are uncommon. Here we presented an unusual case with coexistence of neuroendocrine tumor and signet ring cell carcinoma in the stomach. Gastroscopic examination of a 66-year-old male patient showed a submucosal tumor-like mass with an ulcer on the surface located in the anterior wall of the lower segment of gastric body, confirmed by subsequent biopsy as a signet ring cell carcinoma. Moreover, we also found a slightly yellowish 6-mm protrusion simulating a polyp located in the lesser curvature of the upper segment of gastric body, and biopsy revealed it was a neuroendocrine tumor. The patient underwent a total gastrectomy with a standard D2 lymph node dissection. Pathohistological results led to the final diagnosis of synchronous neoplasms in the stomach, including a signet ring cell carcinoma and a neuroendocrine tumor.
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Affiliation(s)
- Jian Han
- Department of Gastroenterology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ying Wang
- Department of Pathology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Hanlin Mu
- Department of Radiology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jingmei Liu
- Department of Gastroenterology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Hou G, Cheng X, Jiang Y, Yang Y, Chen B, Huang Z, Li Z, Zhou A, Chen X, Zheng R, Zhao H, Zhang J, Wang X. Comparison of Al18F-NOTA-FAPI-74 and 18F-FDG PET/CT in the Evaluation and Staging of Hepatobiliary Malignancies: A Single-center Prospective Study. Clin Nucl Med 2025:00003072-990000000-01677. [PMID: 40279677 DOI: 10.1097/rlu.0000000000005889] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2025] [Accepted: 03/04/2025] [Indexed: 04/27/2025]
Abstract
BACKGROUND Accurate diagnosis and staging are crucial for the management of patients with hepatobiliary malignancies. Here, we investigated the efficacy of Al18F-NOTA-FAPI-74 PET/CT in detecting hepatobiliary malignancies and compared the results with 18F-FDG PET/CT. PATIENTS AND METHODS Participants with hepatobiliary malignancies were prospectively enrolled and underwent paired Al18F-NOTA-FAPI-74 and 18F-FDG PET/CT from April 2023 to March 2024. Histopathology and/or follow-up imaging served as the reference standard. The SUVmax of the primary and metastatic lesions between Al18F-NOTA-FAPI-74 and 18F-FDG PET/CT were compared using the Wilcoxon signed-rank test. The association between Al18F-NOTA-FAPI-74 uptake intensity and immunohistochemical FAP expression was analyzed with Spearman r correlation. RESULTS Our cohort comprised of 28 patients with hepatobiliary malignancies, including 12 with hepatocellular carcinoma, 13 with intrahepatic cholangiocarcinoma (ICC), 2 with perihilar cholangiocarcinoma, and 1 with gallbladder carcinoma. Of these 28 patients, 13 underwent PET/CT for initial staging and 15 for restaging. Al18F-NOTA-FAPI-74 PET/CT showed higher sensitivity than 18F-FDG PET/CT for detecting primary tumors [100% (13/13) vs 92.3% (12/13)], lymph node metastases [79.2% (42/53) vs 54.7% (29/53)], and bone and visceral metastases [97.6% (164/168) vs 69.0% (116/168)]. Al18F-NOTA-FAPI-74 PET/CT findings led to upstaging or restaging in 6 of 28 patients compared with the 18F-FDG PET/CT-based stage. In addition, Al18F-NOTA-FAPI-74 PET/CT detected tumor-related obstructive inflammation in 7 patients, while 18F-FDG PET/CT detected it in only 1 patient (25% vs 3.6%). All these 7 patients suffered from cholangiocarcinomas, including 5 with ICC and 2 with perihilar cholangiocarcinomas. The SUVmax of obstructive inflammation on Al18F-NOTA-FAPI-74 PET/CT was significantly lower than that of tumor (median SUVmax, 4.0 vs 8.8; P = 0.008). A positive correlation was found between FAPI uptake and FAP expression (r = 0.730, P = 0.04). CONCLUSIONS In patients with hepatobiliary malignancies, Al18F-NOTA-FAPI-74 PET/CT outperformed 18F-FDG PET/CT in detecting primary tumors and metastatic lesions, resulting in more accurate staging or restaging. In addition, Al18F-NOTA-FAPI-74 PET/CT showed good detection efficacy for tumor-related obstructive inflammation, which was only found in cholangiocarcinoma, thus rendering Al18F-NOTA-FAPI-74 the potential to differentiate ICC from hepatocellular carcinoma.
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Affiliation(s)
- Guozhu Hou
- Department of Nuclear Medicine (PET-CT Center)
| | - Xin Cheng
- Department of Nuclear Medicine (PET-CT Center)
| | | | - Yi Yang
- Department of Hepatobiliary Surgery
| | - Bo Chen
- Department of Radiation Oncology
| | | | | | - Aiping Zhou
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiaoyuan Chen
- Department of Diagnostic Radiology
- Theranostics Center of Excellence
- Nanomedicine Translational Research Program
- Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Department of Chemical and Biomolecular Engineering
- Department of Biomedical Engineering, College of Design and Engineering, College of Design and Engineering, National University of Singapore
- Department of Pharmacy and Pharmaceutical Sciences, Faculty of Science, National University of Singapore
- Institute of Molecular and Cell Biology, Agency for Science, Technology, and Research (A*STAR), Singapore, Singapore
| | - Rong Zheng
- Department of Nuclear Medicine (PET-CT Center)
| | | | - Jingjing Zhang
- Department of Diagnostic Radiology
- Theranostics Center of Excellence
- Nanomedicine Translational Research Program
- Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
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Gao L, Yao T, Ge S, Cui J, Li W, Guo Z, Xu H, Weng M, Li S, Yao Q, Hu W, Zhou L, Chen J, Wu X, Zhao Q, Li H, Shi H, Ba Y, Huang H. Effect of comorbidity classes on survival of patients with gastrointestinal tract cancer. BMC Cancer 2025; 25:225. [PMID: 39923053 PMCID: PMC11807313 DOI: 10.1186/s12885-025-13517-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Accepted: 01/14/2025] [Indexed: 02/10/2025] Open
Abstract
BACKGROUND Comorbidities may complicate medical situations and have an impact on the treatment decisions and poor survival of cancer patients. How comorbidities cluster together and ultimately affect patients' outcomes in gastrointestinal tract cancer (GTC) is a poorly understood area. METHODS In a multicenter prospective observational study from 2012 to 2021, we grouped the comorbidities of patients with GTC by latent class analysis, obtaining two comorbidity classes. Cox regression models were initially used to predict mortality. LASSO techniques were used to reduce the dimension. The final model included the comorbidity classes and nine more predictors. Additionally, the performance of different simple multimorbidity measures were compared using the Bayesian information criterion (BIC), ROC curves and C-index. Finally, the performance of the final model was analyzed using ROC curves, calibration curves and decision curves. The nomogram was drawn to evaluate the model. RESULTS We included 10,019 patients and obtained two comorbidity classes. Class 2 patients have a higher incidence of comorbidities, and a lower survival rate compared to Class 1 (P < 0.001). Compared to models containing the number of comorbidities or only a single comorbidity, the final model with the comorbidity classes has the highest AUC and C-index, as well as the lowest BIC, indicating this model has the best predictive performance. CONCLUSION We identified two classes of comorbidities that were associated with overall survival in patients with GTC. The combination of different comorbidities class plays a vital role in the prognosis of GTC.
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Affiliation(s)
- Linna Gao
- Department of Gastrointestinal Surgery, First Hospital of Shanxi Medical University, The First Clinical Medical College of Shanxi Medical University, Taiyuan, Shanxi, 030001, China
| | - Tian Yao
- Department of Gastrointestinal Surgery, Center of Clinical Epidemiology and Evidence Based Medicine, First Hospital of Shanxi Medical University, Center of Clinical Epidemiology and Evidence Based Medicine, Shanxi Medical University, Taiyuan, Shanxi, 030001, China
| | - Shaohua Ge
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China
| | - Jiuwei Cui
- Cancer Center, The First Hospital of Jilin University, Changchun, 130021, China
| | - Wei Li
- Cancer Center, The First Hospital of Jilin University, Changchun, 130021, China
| | | | - Hongxia Xu
- Department of Clinical Nutrition, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, 400042, China
| | - Min Weng
- Department of Clinical Nutrition, The First Affiliated Hospital of Kunming Medical University, Kunming, 650500, China
| | - Suyi Li
- Department of Medical Oncology, Anhui Provincial Cancer Hospital, Hefei, 230031, China
| | - Qinghua Yao
- The Second Affiliated Hospital of Zhejiang Chinese Medical University, Xinhua Hospital of Zhejiang Province, Hangzhou, Zhejiang, 310005, China
| | - Wen Hu
- Department of Clinical Nutrition, Sichuan University West China Hospital, Chengdu, 610041, China
| | - Lan Zhou
- Department of Clinical Nutrition, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650118, China
| | - Junqiang Chen
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China
| | - Xianghua Wu
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China
| | - Qingchuan Zhao
- Xijing Hospital, Air Force Medical University, Xi'an, 750102, China
| | - Hongli Li
- Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China
| | - Hanping Shi
- Department of Gastrointestinal Surgery and Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Haidian District, Beijing, Shanxi, 100038, China.
| | - Yi Ba
- Peking Union Medical College Hospital, Beijing, 100730, China.
| | - He Huang
- Department of Gastrointestinal Surgery, First Hospital of Shanxi Medical University, The First Clinical Medical College of Shanxi Medical University, Taiyuan, Shanxi, 030001, China.
- Department of Nutrition and Food Hygiene, School of Public Health, Shanxi Medical University, Taiyuan, Shanxi, 030001, China.
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Kabatnik S, Zheng X, Pappas G, Steigerwald S, Padula MP, Mann M. Deep visual proteomics reveals DNA replication stress as a hallmark of signet ring cell carcinoma. NPJ Precis Oncol 2025; 9:37. [PMID: 39910169 PMCID: PMC11799539 DOI: 10.1038/s41698-025-00819-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Accepted: 01/17/2025] [Indexed: 02/07/2025] Open
Abstract
Signet Ring Cell Carcinoma (SRCC) is a rare and highly malignant form of adenocarcinoma with increasing incidence and poor prognosis due to late diagnosis and limited treatment options. We employed Deep Visual Proteomics (DVP), which combines AI-directed cell segmentation and classification with laser microdissection and ultra-high sensitivity mass spectrometry, for cell-type-specific proteomic analysis of SRCC across the bladder, prostate, seminal vesicle, and a lymph node of a single patient. DVP identified significant alterations in DNA damage response (DDR) proteins, particularly within the ATR and mismatch repair (MMR) pathways, indicating replication stress as a crucial factor in SRCC mutagenicity. Additionally, we observed substantial enrichment of immune-related proteins, reflecting high levels of cytotoxic T lymphocyte infiltration and elevated PD-1 expression. These findings suggest that pembrolizumab immunotherapy may be more effective than conventional chemotherapy for this patient. Our results provide novel insights into the proteomic landscape of SRCC, identify potential targets, and open up for personalized therapeutic strategies in managing SRCC.
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Affiliation(s)
- Sonja Kabatnik
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark
| | - Xiang Zheng
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark
- Department of Biomedicine, Aarhus University, Aarhus, Denmark
| | - Georgios Pappas
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark
| | - Sophia Steigerwald
- Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany
| | - Matthew P Padula
- School of Life Sciences and Proteomics Core Facility, Faculty of Science, University of Technology Sydney, Ultimo, Australia.
| | - Matthias Mann
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark.
- Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany.
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Yu Y, Gong C, Deng R, Lu Z, Deng D, Hou J, Cheng W, Li G, Liang J. Testicular metastasis of gastric signet-ring cell carcinoma. INDIAN J PATHOL MICR 2025; 68:244-245. [PMID: 38847178 DOI: 10.4103/ijpm.ijpm_229_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Accepted: 03/12/2024] [Indexed: 04/01/2025] Open
Affiliation(s)
- Yi Yu
- Organ Transplant Center, Zhongshan People's Hospital, Zhongshan, China
| | - Chaoyang Gong
- Organ Transplant Center, Zhongshan People's Hospital, Zhongshan, China
| | - Rongfang Deng
- Department of Surgical Anesthesiology, Zhongshan People's Hospital, Zhongshan, China
| | - Ziji Lu
- Department of Pathology, Zhongshan People's Hospital, Zhongshan, China
| | - Decheng Deng
- Organ Transplant Center, Zhongshan People's Hospital, Zhongshan, China
| | - Jingcai Hou
- Organ Transplant Center, Zhongshan People's Hospital, Zhongshan, China
| | - Weixiang Cheng
- Organ Transplant Center, Zhongshan People's Hospital, Zhongshan, China
| | - Guojun Li
- Organ Transplant Center, Zhongshan People's Hospital, Zhongshan, China
| | - Jiamin Liang
- Organ Transplant Center, Zhongshan People's Hospital, Zhongshan, China
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Yu C, Yang J, Li H, Wang J, Jin K, Li Y, Zhang Z, Zhou J, Tang Y. Prognostic prediction and treatment options for gastric signet ring cell carcinoma: a SEER database analysis. Front Oncol 2024; 14:1473798. [PMID: 39497709 PMCID: PMC11532132 DOI: 10.3389/fonc.2024.1473798] [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: 07/31/2024] [Accepted: 10/02/2024] [Indexed: 11/07/2024] Open
Abstract
Background In recent years, the overall incidence of gastric cancer has decreased. However, the incidence of gastric signet ring cell carcinoma (SRCC) is still increasing year by year. Compared with other subtypes (non-SRCC) such as adenocarcinoma, SRCC usually exhibits a more aggressive biological behavior. Therefore, studying the prognostic differences and factors associated with SRCC is essential to improve the accuracy of diagnosis and prognosis. The purpose of this study was to investigate the prognostic factors influencing the prognosis of patients with SRCC and to develop personalized treatments for different subgroups of patients. Methods The data on gastric SRCC patients and gastric adenocarcinoma (AC) patients from 1992 to 2020 was obtained from the Surveillance, Epidemiology, and End Results (SEER) database. The data of gastric SRCC as the external validation group was reviewed from the First Affiliated Hospital of Soochow University. The overall survival (OS) and cancer specific survival (CSS) at 1 and 2 years were predicted for SRCC patients by constructing prognostic nomograms. A series of validation methods, including Akaike information criterion (AIC), decision curve analysis (DCA), calibration curve analysis, the concordance index (C-index) and the area under the receiver operating characteristic (AUC) curve, were used to verify the accuracy and reliability of the models. Results In all, 549 patients with SRCC were included after propensity score matching (PSM). Multivariate Cox regression analysis showed that T stage, N stage, M stage and surgical approach were independent risk factors affecting the prognosis of SRCC patients. A prognostic nomogram was constructed and validated as an accurate model for SRCC patients after scoring by receiver operating characteristic curve (ROC) curves and calibration plots. The patients were further divided into high-risk and low-risk groups, and the Kaplan-Meier curves showed that SRCC patients in the low-risk group could receive only surgery without chemotherapy, while chemotherapy plus surgery was a better option for SRCC patients in the high-risk group. Conclusion The prognosis for SRCC was less favorable than that of AC in terms of CSS. The nomograms were developed and validated to predict OS and CSS in patients with SRCC, helping in developing appropriate individualized treatment schedules.
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Affiliation(s)
- Chengqing Yu
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Jian Yang
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
- State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, China
| | - Haoran Li
- Department of Gastrointestinal Surgery, Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou Medical Center, Changzhou, China
| | - Jie Wang
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Kanghui Jin
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Yifan Li
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Zixiang Zhang
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Jian Zhou
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
- State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, China
| | - Yuchen Tang
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
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Guío-Ávila JI, Soler-Perilla AY, Briceño-Morales X, Briceño-Morales C. Gastric signet ring cell adenocarcinoma metastatic to the breast. Systematic review of the literature, regarding a case. REVISTA COLOMBIANA DE OBSTETRICIA Y GINECOLOGIA 2024; 75:4187. [PMID: 39470266 PMCID: PMC11584199 DOI: 10.18597/rcog.4187] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/19/2024] [Accepted: 09/02/2024] [Indexed: 10/30/2024]
Abstract
Objectives To determine the general state of scientific evidence published in the last 20 years on gastric signet ring cell (SRC) adenocarcinoma metastatic to the breast, and present a case. Material and methods The case of a patient who attended a high-complexity reference institution in Bogotá for a breast metastasis from a gastric SRC adenocarcinoma is reported. A Systematic Review of the literature was carried out, including cohort studies, reports and case series of patients with gastric SRC adenocarcinoma metastatic to the breast, which will present information on the epidemiology, clinical, radiological and histopathological characteristics, and the treatment and prognostic of this disease. Results There were identified 363 references, twenty-six of which met the eligibility criteria. Gastric SRC adenocarcinoma metastatic to the breast predominated in the Asian continent (75.9%). The mean age at presentation was 42.5 years. In 62% (n=18) of cases this condition manifested clinically as a breast mass. From a radiological point of view, the majority of breast lesions presented as one or several nodules with suspicious characteristics (55.2%; n=16). In the biopsy of breast lesions, positivity for cytokeratin 7 and cytokeratin 20 occurred in 41.4% (n=12) and 37.9% (n=11) of cases, respectively. Only nine patients (31%) underwent any type of breast surgery. There is a lack of information on the treatment and prognosis of gastric SRC adenocarcinoma metastatic to the breast. Conclusions The frequency of cases of gastric SRC adenocarcinoma metastatic to the breast published in the last 20 years is low. The general practitioner and the gynecologist could be the first medical professionals to face this rare condition, so knowing it and suspecting it is essential, especially if we take into account that the median overall survival of these patients is low.
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Affiliation(s)
- José Ismael Guío-Ávila
- Profesor Titular, Departamento de Ginecología y Obstetricia, Hospital de San José de Bogotá, Fundación Universitaria de Ciencias de la Salud. Bogotá (Colombia)
| | - Adriana Yulieth Soler-Perilla
- Residente de cuarto año de Ginecología y Obstetricia, Hospital de San José de Bogotá, Fundación Universitaria de Ciencias de la Salud. Bogotá (Colombia)
| | - Ximena Briceño-Morales
- Especialista en Mastología, Instituto Nacional de Cancerología. Bogotá (Colombia); Departamento de Obstetricia y Ginecología, Facultad de Medicina, Universidad Nacional de Colombia. Bogotá (Colombia)
| | - Clara Briceño-Morales
- Especialista en Cirugía Oncológica. Grupo de Investigación en Ciencias Quirúrgicas, Universidad Tecnológica de Pereira. Pereira (Colombia); Institución Universitaria Visión de las Américas. Pereira (Colombia)
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Chu Y, Long F, Ding X, Tian S. The effect of surgery and metastatic risk prediction in patients with gastrointestinal tract signet-ring cell carcinoma. J Gastrointest Surg 2024; 28:1234-1241. [PMID: 38740257 DOI: 10.1016/j.gassur.2024.05.011] [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: 02/04/2024] [Revised: 04/12/2024] [Accepted: 05/08/2024] [Indexed: 05/16/2024]
Abstract
PURPOSE This study aimed to assess the efficacy of surgery as a treatment option for patients with signet-ring cell carcinoma (SRCC) in the gastrointestinal tract (GI-SRCC). METHODS Using the Surveillance, Epidemiology, and End Results database, patients with GI-SRCC who underwent surgery or received nonsurgical treatment were included. Propensity score matching (PSM) analysis was used to balance baseline characteristics and reduce bias. Overall survival (OS) was calculated in matching cohorts to estimate prognosis for patients with GI-SRCC. Nomogram was established to predict metastasis for patients with GI-SRCC. RESULTS The study enrolled a total of 9428 patients with GI-SRCC, with 1689 patients in the nonsurgery group and 7739 patients in the surgery group. After 1:1 PSM, we analyzed 743 patients from each group. Our survival analyses revealed that surgery independently correlated with improved OS for patients with GI-SRCC (hazard ratio, 0.37; 95% CI, 0.33-0.42; P < .001). Subgroup analysis further confirmed the positive impact of surgery on the prognosis of patients with nonmetastatic GI-SRCC. Notably, distinct subsets of patients with metastasis, particularly those originating from the upper GI (esophagus, proximal stomach, and distal stomach) and left colon, demonstrated a significant improvement in OS after surgery. However, no significant survival difference was observed for patients with metastatic right colon and rectum SRCC. Using nomogram, we quantitatively assessed the risk of metastasis in patients with right colon and rectum SRCC, which exhibited robust predictive accuracy, with area under the curve values of 0.829. CONCLUSION Our study highlighted surgery's positive impact on prognosis for both patients with nonmetastatic and metastatic upper GI-SRCC and left colon SRCC. Hence, we recommend surgery as a treatment option for these groups. In addition, for patients with metastatic right colon and rectum SRCC ineligible for surgery, our predictive nomogram can offer a convenient tool to aid early intervention and improve prognosis.
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Affiliation(s)
- Yanan Chu
- Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Fei Long
- Laboratory of Pediatric Hematology, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xueliang Ding
- Department of Clinical Laboratory, Affiliated Renhe Hospital of China Three Gorges University, Yichang, China
| | - Shaobo Tian
- Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
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Yen H, Chen P, Huang RY, Jeng J, Lai I. Clinicopathological features and cancer transcriptomic profiling of poorly cohesive gastric carcinoma subtypes. J Pathol Clin Res 2024; 10:e12387. [PMID: 38860888 PMCID: PMC11165978 DOI: 10.1002/2056-4538.12387] [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: 03/18/2024] [Revised: 05/16/2024] [Accepted: 05/20/2024] [Indexed: 06/12/2024]
Abstract
Gastric poorly cohesive carcinoma (PCC) manifests with a diffuse pattern and diverse tumor cell morphologies, often indicating a more unfavorable prognosis. Recent consensus has reclassified PCC based on the proportion of signet-ring cells (SRCs) in tumors for research purposes. The two most distinct subtypes, poorly cohesive carcinoma not otherwise specified (PCC-NOS) and signet-ring cell carcinoma (SRCC), are characterized by less than 10% and more than 90% SRCs, respectively. However, research comparing the clinicopathological and transcriptomic differences between these subtypes remains limited. In this study, we conducted a comparative analysis of clinicopathological features in 55 advanced-stage PCCs, consisting of 43 PCC-NOS and 12 SRCC cases. Subsequently, 12 PCC-NOS and 5 SRCC cases were randomly selected for initial cancer-related gene expression profiling and pathway enrichment analysis using the GeoMx digital spatial profiler, followed by validation in a separate validation group comprising 16 PCC-NOS and 6 SRCC cases. These transcriptomic findings were then correlated with tumor morphology and clinicopathological data. PCC-NOS cases exhibited larger tumor size, a higher prevalence of pathological N3 disease, and a worse 1-year progression-free survival rate compared to SRCC cases. Clustering of PCC-NOS and SRCC was successfully achieved using the GeoMx Cancer Transcriptome Atlas. Among all studied genes, only MMP7 showed differential expression, with its overexpression significantly associated with the PCC-NOS subtype, increased perineural invasion, and earlier disease progression. Pathway analysis revealed significantly enriched pathways in PCC-NOS related to vesicle-mediated transport, adaptive immune systems, oncogenic signaling, and extracellular matrix organization, while SRCC displayed significant enrichment in pathways associated with respiratory electron transport and the cell cycle. In conclusion, this study compares and correlates clinicopathological features and transcriptomic data between PCC-NOS and SRCC at advanced stages, employing the latest consensus classification and a novel platform for analysis.
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Affiliation(s)
- Hung‐Hsuan Yen
- Department of SurgeryNational Taiwan University Hospital Hsin‐Chu BranchHsinchuTaiwan
- Department of SurgeryNational Taiwan University HospitalTaipeiTaiwan
| | - Pin‐Yu Chen
- Graduate Institute of Anatomy and Cell Biology, College of MedicineNational Taiwan UniversityTaipeiTaiwan
| | - Ruby Yun‐Ju Huang
- School of Medicine, College of MedicineNational Taiwan UniversityTaipeiTaiwan
| | - Jung‐Ming Jeng
- Department of PathologyNational Taiwan University HospitalTaipeiTaiwan
| | - I‐Rue Lai
- Department of SurgeryNational Taiwan University HospitalTaipeiTaiwan
- Graduate Institute of Anatomy and Cell Biology, College of MedicineNational Taiwan UniversityTaipeiTaiwan
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11
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Imai Y, Kurata Y, Ichinose M. Prognostic relevance of the most predominant and least differentiated grades of gastric adenocarcinoma after curative gastrectomy. Surg Oncol 2024; 54:102067. [PMID: 38527388 DOI: 10.1016/j.suronc.2024.102067] [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: 10/10/2023] [Revised: 03/14/2024] [Accepted: 03/19/2024] [Indexed: 03/27/2024]
Abstract
BACKGROUND Prognostic relevance of differentiation grade has remained controversial in gastric adenocarcinoma (GAC) after curative resection. METHODS GAC patients who underwent curative gastrectomy were analyzed. Differentiation grade was evaluated according to either the most predominant or least differentiated component. Impacts of clinicopathologic parameters on postoperative recurrence and nodal metastasis were analyzed by the multivariate Cox regression analysis in pT1/2/3/4a and pT1b/2/3 GAC and by the logistic regression analysis in pT1b GAC, respectively. RESULTS 154 patients with GAC, consisting of 34 pT1a (recurrence rate 0%), 45 pT1b (4.4%), 18 pT2 (22.2%), 40 pT3 (35.0%), and 17 pT4a (76.5%), were included. In pT1/2/3/4a GAC, recurrence was significantly associated with only depth of invasion (pT) and grade of venous invasion (VI), although either mode of differentiation grade was significantly associated with pT by the Spearman's rank correlation test. Next, given no recurrence in pT1a and high-grade histopathology in nearly all pT4a, pT1b/2/3 GAC was analyzed, revealing that recurrence was significantly associated with only VI grade and nodal metastasis. Finally, nodal metastasis was not found in any pT1a GAC, of which 44.1% was predominantly high-grade. In pT1b GAC, nodal metastasis was irrelevant to either mode of differentiation grade, tumor size, and ulceration status but was only associated with lymphatic invasion, suggesting that endoscopic resection of pT1 GAC with negative margin can be curative even with high-grade histopathology. CONCLUSION Either mode of differentiation grade revealed limited prognostic relevance after curative gastrectomy. Our results may warrant a controversy over current curability evaluation of endoscopic GAC resection.
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Affiliation(s)
- Yasuo Imai
- Department of Diagnostic Pathology, Ota Memorial Hospital, SUBARU Health Insurance Society, 455-1 Oshima, Ota, Gunma, 373-8585, Japan.
| | - Yoshihiro Kurata
- Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan; Department of Digestive Surgery, Shioya Hospital, International University of Health and Welfare, Tochigi, Japan
| | - Masanori Ichinose
- Department of Digestive Surgery, Shioya Hospital, International University of Health and Welfare, Tochigi, Japan
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12
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Xu W, Cai J, Peng T, Meng T, Pang Y, Sun L, Wu H, Zhang J, Chen X, Chen H. Fibroblast Activation Protein-Targeted PET/CT with 18F-Fibroblast Activation Protein Inhibitor-74 for Evaluation of Gastrointestinal Cancer: Comparison with 18F-FDG PET/CT. J Nucl Med 2024; 65:40-51. [PMID: 37884330 DOI: 10.2967/jnumed.123.266329] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2023] [Revised: 09/27/2023] [Indexed: 10/28/2023] Open
Abstract
Fibroblast activation protein is overexpressed in the stroma of several cancer types. 18F-fibroblast activation protein inhibitor (FAPI)-74 is a PET tracer with high selectivity for fibroblast activation protein and has shown high accumulation in human tumors in clinical studies. However, the use of 18F-FAPI-74 for PET imaging of gastrointestinal cancer has not been systematically investigated. Herein, we investigated the diagnostic accuracy of 18F-FAPI-74 (18F-LNC1005) PET/CT in gastric, liver, and pancreatic cancers and compared the results with those of 18F-FDG PET/CT. Methods: This prospective study analyzed patients with confirmed gastric, liver, or pancreatic malignancies who underwent concurrent 18F-FDG and 18F-FAPI-74 PET/CT between June 2022 and December 2022. PET/CT findings were confirmed by histopathology or radiographic follow-up. 18F-FDG and 18F-FAPI-74 uptake and tumor-to-background ratios were compared using the Wilcoxon signed-rank test. The McNemar test was used to compare the diagnostic accuracy of the 2 scans. Results: Our cohort consisted of 112 patients: 49 with gastric cancer, 39 with liver cancer, and 24 with pancreatic cancer. Among them, 69 patients underwent PET/CT for initial staging and 43 for recurrence detection. Regarding lesion-based diagnostic accuracy, 18F-FAPI-74 PET/CT showed higher sensitivity than did 18F-FDG in the detection of primary tumors (gastric cancer, 88% [22/25] vs. 60% [15/25], P = 0.016; liver cancer, 100% [22/22] vs. 82% [18/22], P = 0.125; pancreatic cancer, 100% [22/22] vs. 86% [19/22], P = 0.250), local recurrence (92% [23/25] vs. 56% [14/25]; P = 0.021), involved lymph nodes (71% [41/58] vs. 40% [23/58]; P < 0.001), and bone and visceral metastases (98% [350/358] vs. 47% [168/358]; P < 0.001). Compared with 18F-FDG, 18F-FAPI-74 PET/CT upstaged 17 patients' TNM staging among all treatment-naïve patients (17/69, 25%) and changed the clinical management of 4 patients (4/43, 9%) in whom recurrence or metastases were detected. Conclusion: 18F-FAPI-74 PET/CT is superior to 18F-FDG PET/CT in detecting primary tumors, local recurrence, lymph node involvement, and bone and visceral metastases in gastric, pancreatic, and liver cancers, with higher uptake in most primary and metastatic lesions.
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Affiliation(s)
- Weizhi Xu
- Department of Nuclear Medicine, First Affiliated Hospital of Xiamen University, Xiamen, China
- Minnan PET Center, First Affiliated Hospital of Xiamen University, Xiamen, China
- Xiamen Key Laboratory of Radiopharmaceuticals, School of Medicine, Xiamen University, Xiamen, China
| | - Jiayu Cai
- Department of Nuclear Medicine, First Affiliated Hospital of Xiamen University, Xiamen, China
- Minnan PET Center, First Affiliated Hospital of Xiamen University, Xiamen, China
- Xiamen Key Laboratory of Radiopharmaceuticals, School of Medicine, Xiamen University, Xiamen, China
| | - Tianxing Peng
- Department of Nuclear Medicine, First Affiliated Hospital of Xiamen University, Xiamen, China
- Minnan PET Center, First Affiliated Hospital of Xiamen University, Xiamen, China
- Xiamen Key Laboratory of Radiopharmaceuticals, School of Medicine, Xiamen University, Xiamen, China
| | - Tinghua Meng
- Department of Nuclear Medicine, First Affiliated Hospital of Xiamen University, Xiamen, China
- Minnan PET Center, First Affiliated Hospital of Xiamen University, Xiamen, China
- Xiamen Key Laboratory of Radiopharmaceuticals, School of Medicine, Xiamen University, Xiamen, China
| | - Yizhen Pang
- Department of Nuclear Medicine, First Affiliated Hospital of Xiamen University, Xiamen, China
- Minnan PET Center, First Affiliated Hospital of Xiamen University, Xiamen, China
- Xiamen Key Laboratory of Radiopharmaceuticals, School of Medicine, Xiamen University, Xiamen, China
| | - Long Sun
- Department of Nuclear Medicine, First Affiliated Hospital of Xiamen University, Xiamen, China
- Minnan PET Center, First Affiliated Hospital of Xiamen University, Xiamen, China
- Xiamen Key Laboratory of Radiopharmaceuticals, School of Medicine, Xiamen University, Xiamen, China
| | - Hua Wu
- Department of Nuclear Medicine, First Affiliated Hospital of Xiamen University, Xiamen, China
- Minnan PET Center, First Affiliated Hospital of Xiamen University, Xiamen, China
- Xiamen Key Laboratory of Radiopharmaceuticals, School of Medicine, Xiamen University, Xiamen, China
| | - Jingjing Zhang
- Department of Diagnostic Radiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Department of Chemical and Biomolecular Engineering, College of Design and Engineering, National University of Singapore, Singapore
- Department of Biomedical Engineering, College of Design and Engineering, National University of Singapore, Singapore; and
| | - Xiaoyuan Chen
- Department of Diagnostic Radiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore;
- Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Department of Chemical and Biomolecular Engineering, College of Design and Engineering, National University of Singapore, Singapore
- Institute of Molecular and Cell Biology, Agency for Science, Technology, and Research (A*STAR), Singapore
| | - Haojun Chen
- Department of Nuclear Medicine, First Affiliated Hospital of Xiamen University, Xiamen, China;
- Minnan PET Center, First Affiliated Hospital of Xiamen University, Xiamen, China
- Xiamen Key Laboratory of Radiopharmaceuticals, School of Medicine, Xiamen University, Xiamen, China
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13
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Hong W, Hu Q, Tan Y, Duan Q, Zhang Q, Chen D, Qi C, Wang D. Gastrointestinal signet ring cell malignancy: current advancement and future prospects. Invest New Drugs 2023; 41:861-869. [PMID: 37864727 DOI: 10.1007/s10637-023-01403-1] [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: 08/08/2023] [Accepted: 10/18/2023] [Indexed: 10/23/2023]
Abstract
Globally, gastrointestinal cancer is the most widespread neoplastic disease and the primary contributor to cancer-associated fatalities. Gastrointestinal signet ring cell carcinoma (SRCC) exhibits unique distinguishing features in several aspects when compared to adenocarcinomas (ACs). The scarcity of signet ring cell carcinoma has resulted in a heightened significance of related clinical and molecular investigations. However, a comprehensive and systematic review of the clinical, molecular, therapeutic, and research aspects of this disease is currently absent. This review provides an overview of the latest developments in our understanding of the clinical and molecular features of gastrointestinal signet ring cell carcinoma (SRCC). Additionally, we have compiled a list of potential therapeutic targets or biomarkers, as well as an examination of the current treatment options and the possible mechanisms of formation.
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Affiliation(s)
- Weiping Hong
- Department of Oncology, Guangdong Sanjiu Brain Hospital, 578 Shatai Road, Baiyun District, Guangzhou City, Guangdong Province, China
| | - Qingjun Hu
- Department of Oncology, Guangdong Sanjiu Brain Hospital, 578 Shatai Road, Baiyun District, Guangzhou City, Guangdong Province, China
| | - Yuan Tan
- The Medical Department, Jiangsu Simcere Diagnostics Co., Ltd., Nanjing Simcere Medical Laboratory Science Co., Ltd., The State Key Lab of Translational Medicine and Innovative Drug Development, Jiangsu Simcere Diagnostics Co., Ltd., Nanjing, China
| | - Qianqian Duan
- The Medical Department, Jiangsu Simcere Diagnostics Co., Ltd., Nanjing Simcere Medical Laboratory Science Co., Ltd., The State Key Lab of Translational Medicine and Innovative Drug Development, Jiangsu Simcere Diagnostics Co., Ltd., Nanjing, China
| | - Qin Zhang
- The Medical Department, Jiangsu Simcere Diagnostics Co., Ltd., Nanjing Simcere Medical Laboratory Science Co., Ltd., The State Key Lab of Translational Medicine and Innovative Drug Development, Jiangsu Simcere Diagnostics Co., Ltd., Nanjing, China
| | - Dongsheng Chen
- The Medical Department, Jiangsu Simcere Diagnostics Co., Ltd., Nanjing Simcere Medical Laboratory Science Co., Ltd., The State Key Lab of Translational Medicine and Innovative Drug Development, Jiangsu Simcere Diagnostics Co., Ltd., Nanjing, China
| | - Chuang Qi
- The Medical Department, Jiangsu Simcere Diagnostics Co., Ltd., Nanjing Simcere Medical Laboratory Science Co., Ltd., The State Key Lab of Translational Medicine and Innovative Drug Development, Jiangsu Simcere Diagnostics Co., Ltd., Nanjing, China
| | - Da Wang
- Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Rd., Hangzhou, China.
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14
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Dal Cero M, Bencivenga M, Liu DHW, Sacco M, Alloggio M, Kerckhoffs KGP, Filippini F, Saragoni L, Iglesias M, Tomezzoli A, Carneiro F, Grabsch HI, Verlato G, Torroni L, Piessen G, Pera M, de Manzoni G. Clinical Features of Gastric Signet Ring Cell Cancer: Results from a Systematic Review and Meta-Analysis. Cancers (Basel) 2023; 15:5191. [PMID: 37958365 PMCID: PMC10647446 DOI: 10.3390/cancers15215191] [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: 09/05/2023] [Revised: 10/17/2023] [Accepted: 10/26/2023] [Indexed: 11/15/2023] Open
Abstract
BACKGROUND Conflicting results about the prognostic relevance of signet ring cell histology in gastric cancer have been reported. We aimed to perform a meta-analysis focusing on the clinicopathological features and prognosis of this subgroup of cancer compared with other histologies. METHODS A systematic literature search in the PubMed database was conducted, including all publications up to 1 October 2021. A meta-analysis comparing the results of the studies was performed. RESULTS A total of 2062 studies referring to gastric cancer with signet ring cell histology were identified, of which 262 studies reported on its relationship with clinical information. Of these, 74 were suitable to be included in the meta-analysis. A slightly lower risk of developing nodal metastases in signet ring cell tumours compared to other histotypes was found (especially to undifferentiated/poorly differentiated/mucinous and mixed histotypes); the lower risk was more evident in early and slightly increased in advanced gastric cancer. Survival tended to be better in early stage signet ring cell cancer compared to other histotypes; no differences were shown in advanced stages, and survival was poorer in metastatic patients. In the subgroup analysis, survival in signet ring cell cancer was slightly worse compared to non-signet ring cell cancer and differentiated/well-to-moderately differentiated adenocarcinoma. CONCLUSIONS Most of the conflicting results in signet ring cell gastric cancer literature could be derived from the lack of standardisation in their classification and the comparison with the different subtypes of gastric cancer. There is a critical need to strive for a standardised classification system for gastric cancer, fostering clarity and coherence in the forthcoming research and clinical applications.
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Affiliation(s)
- Mariagiulia Dal Cero
- General and Upper GI Surgery Division, Department of Surgery, University of Verona, Borgo Trento Hospital, Piazzale Stefani 1, 37124 Verona, Italy; (M.D.C.)
- Section of Gastrointestinal Surgery, Hospital Universitario del Mar, Hospital del Mar Medical Research Institute (IMIM), Department of Surgery, Universitat Autònoma de Barcelona, 08003 Barcelona, Spain
| | - Maria Bencivenga
- General and Upper GI Surgery Division, Department of Surgery, University of Verona, Borgo Trento Hospital, Piazzale Stefani 1, 37124 Verona, Italy; (M.D.C.)
| | - Drolaiz H. W. Liu
- Department of Pathology, GROW School for Oncology and Reproduction, Maastricht University Medical Center, 6229 HX Maastricht, The Netherlands
- Institute of Clinical Pathology and Molecular Pathology, Kepler University Hospital and Johannes Kepler University, 4021 Linz, Austria
| | - Michele Sacco
- General and Upper GI Surgery Division, Department of Surgery, University of Verona, Borgo Trento Hospital, Piazzale Stefani 1, 37124 Verona, Italy; (M.D.C.)
| | - Mariella Alloggio
- General and Upper GI Surgery Division, Department of Surgery, University of Verona, Borgo Trento Hospital, Piazzale Stefani 1, 37124 Verona, Italy; (M.D.C.)
| | - Kelly G. P. Kerckhoffs
- Department of Pathology, GROW School for Oncology and Reproduction, Maastricht University Medical Center, 6229 HX Maastricht, The Netherlands
- Department of Pathology, VieCuri Medical Centre, 5912 BL Venlo, The Netherlands
| | - Federica Filippini
- General and Upper GI Surgery Division, Department of Surgery, University of Verona, Borgo Trento Hospital, Piazzale Stefani 1, 37124 Verona, Italy; (M.D.C.)
| | - Luca Saragoni
- Pathology Unit, Morgagni-Pierantoni Hospital, 47100 Forlì, Italy
| | - Mar Iglesias
- Department of Pathology, Hospital Universitario del Mar, Hospital del Mar Medical Research Institute (IMIM), 08003 Barcelona, Spain
| | - Anna Tomezzoli
- Department of Pathology, Verona University Hospital, 37134 Verona, Italy
| | - Fátima Carneiro
- Department of Pathology, Medical Faculty of the University of Porto/Centro Hospitalar Universitário São João and Ipatimup/i3S, 4200-319 Porto, Portugal
| | - Heike I. Grabsch
- Department of Pathology, GROW School for Oncology and Reproduction, Maastricht University Medical Center, 6229 HX Maastricht, The Netherlands
- Division of Pathology and Data Analytics, Leeds Institute of Medical Research at St. James’s, University of Leeds, Leeds LS2 9JT, UK
| | - Giuseppe Verlato
- Unit of Epidemiology and Medical Statistics, Department of Diagnostics and Public Health, University of Verona, 37126 Verona, Italy
| | - Lorena Torroni
- Unit of Epidemiology and Medical Statistics, Department of Diagnostics and Public Health, University of Verona, 37126 Verona, Italy
| | - Guillaume Piessen
- Department of Digestive and Oncological Surgery, Lille University Hospital, 59000 Lille, France
| | - Manuel Pera
- Section of Gastrointestinal Surgery, Hospital Universitario del Mar, Hospital del Mar Medical Research Institute (IMIM), Department of Surgery, Universitat Autònoma de Barcelona, 08003 Barcelona, Spain
| | - Giovanni de Manzoni
- General and Upper GI Surgery Division, Department of Surgery, University of Verona, Borgo Trento Hospital, Piazzale Stefani 1, 37124 Verona, Italy; (M.D.C.)
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15
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Ma Y, Wang Y, Hu C, Zi M, Chen J, Cao M, Yuan L, Yang L, Du Y. The percentages of signet-ring cells (SRCs) affects the prognosis after radical gastrectomy for advanced gastric cancer. Langenbecks Arch Surg 2023; 408:376. [PMID: 37743407 DOI: 10.1007/s00423-023-03114-w] [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: 05/17/2023] [Accepted: 09/19/2023] [Indexed: 09/26/2023]
Abstract
PURPOSE Only recently has the percentage of signet-ring cells (SRCs) been shown to affect the prognosis following gastric cancer surgery. It is uncertain whether the SRC percentage has a role in tumour biology or prognosis of gastric signet-ring cell carcinoma (GSRCC). For this research, we assessed the effect of the SRC percentage on the clinicopathological and prognostic characteristics of gastric cancer (GC) tumours and created and verified a prognostic nomogram to assess the overall survival (OS) of GSRCC patients. METHODS In our study, 1100 GC patients with signet-ring cell carcinoma (SRCC) at Zhejiang Cancer Hospital from December 2013 to December 2018 who underwent curative gastric cancer resection were retrospectively analysed. The patients were separated into two groups: those with SRCC (SRC percentage >50%; n = 157) and those with partial signet-ring cell carcinoma (PSRCC) (SRC percentage ≤50%; n = 943). We compared the clinicopathological characteristics of both groups. To estimate OS and determine correlations with the SRC percentage, the Kaplan-Meier method and log-rank test were used. To develop the prognostic nomogram, independent prognostic indicators for OS were identified using Cox regression analyses. Predictions were assessed using the calibration curve and C-index. RESULTS Our research showed that there was no discernible difference in OS between the two groups. The preoperative CA242 level, pT stage, pN stage, age, nerve invasion, neoadjuvant chemotherapy, postoperative chemotherapy, and maximum tumour diameter were independent prognostic risk factors for OS for GC (all p < 0.05). However, for advanced GC, the SRC percentage (HR = 1.571, 95% CI 1.072-2.302, p = 0.020) was an independent prognostic factor of OS. Other independent prognostic risk factors were age, pT stage, pN stage, nerve invasion, tumour location, neoadjuvant chemotherapy, postoperative chemotherapy, preoperative CA50 level, and preoperative CEA level (all p < 0.05). On these bases, nomograms were constructed for GC and advanced GC, with C-indexes of 0.806 (95%CI 0.782-0.830) and 0.728 (95%CI 0.697-0.759), respectively. CONCLUSIONS In cases of advanced gastric cancer, the SRC percentage served as a standalone prognostic indicator for OS. An effective tool for assessing the prognosis of GSRCC was offered by the nomogram.
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Affiliation(s)
- Yubo Ma
- The Second Clinical Medical College of Zhejiang Chinese Medical University, Zhejiang, 310053, Hangzhou, China
| | - Yi Wang
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Zhejiang, 310022, Hangzhou, China
| | - Can Hu
- The Second Clinical Medical College of Zhejiang Chinese Medical University, Zhejiang, 310053, Hangzhou, China
| | - Mengli Zi
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Zhejiang, 310022, Hangzhou, China
| | - Jinxia Chen
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Zhejiang, 310022, Hangzhou, China
| | - Mengxuan Cao
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Zhejiang, 310022, Hangzhou, China
| | - Li Yuan
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Zhejiang, 310022, Hangzhou, China.
| | - Litao Yang
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Zhejiang, 310022, Hangzhou, China.
| | - Yian Du
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Zhejiang, 310022, Hangzhou, China.
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16
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Jo HH, Kim N, Oh HJ, Song DH, Choi Y, Park J, Lee J, Yoon H, Shin CM, Park YS, Lee DH, Lee HS, Park YS, Ahn SH, Suh YS, Park DJ, Kim HH, Kim JW, Kim JW, Lee KW, Chang W, Park JH, Lee YJ, Lee KH, Kim YH, Ahn S. The Clinicopathological Features of Mixed Carcinoma in 7,215 Patients with Gastric Cancer in a Tertiary Hospital in South Korea. Gut Liver 2023; 17:731-740. [PMID: 36510778 PMCID: PMC10502493 DOI: 10.5009/gnl220254] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2022] [Revised: 08/10/2022] [Accepted: 10/18/2022] [Indexed: 12/15/2022] Open
Abstract
Background/Aims There are few reports regarding mixed carcinoma, defined as a mixture of glandular and poorly cohesive components, in patients with gastric cancer (GC). The aim of this study was to evaluate the proportion and characteristics of mixed carcinoma in GC patients. Methods A total of 7,215 patients diagnosed with GC at Seoul National University Bundang Hospital were enrolled from March 2011 to February 2020. GC was divided into four groups (well-moderately differentiated GC, poorly differentiated GC, poorly cohesive carcinoma, and mixed carcinoma). The proportion of each GC type and the clinicopathological features were analyzed and divided into early GC and advanced GC. Results The proportion of mixed carcinoma was 10.9% (n=787). In early GC, submucosal invasion was the most common in poorly differentiated (53.7%), and mixed carcinoma ranked second (41.1%). Mixed carcinoma showed the highest proportion of lymph node metastasis in early GC (23.0%) and advanced GC (78.3%). In advanced GC, the rate of distant metastasis was 3.6% and 3.9% in well-moderately differentiated GC and mixed carcinoma, respectively, lower than that in poorly differentiated GC (6.4%) and poorly cohesive carcinoma (5.7%), without statistical significance. Conclusions Mixed carcinoma was associated with lymph node metastasis compared to other histological GC subtypes. And it showed relatively common submucosal invasion in early GC, but the rates of venous invasion and distant metastasis were lower in advanced GC. Further research is needed to uncover the mechanism underlying these characteristics of mixed carcinoma (Trial registration number: NCT04973631).
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Affiliation(s)
- Hyeong Ho Jo
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Internal Medicine, Daegu Catholic University School of Medicine, Daegu, Korea
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Hyeon Jeong Oh
- Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Du Hyun Song
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Yonghoon Choi
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Jaehyung Park
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Jongchan Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Hyuk Yoon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Cheol Min Shin
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Young Soo Park
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Dong Ho Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Hye Seung Lee
- Department of Pathology, Seoul National University College of Medicine, Seoul, Korea
| | - Young Suk Park
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Sang-Hoon Ahn
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Yun-Suhk Suh
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Do Joong Park
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Hyung Ho Kim
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Ji-Won Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Jin Won Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Keun-Wook Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Won Chang
- Department of Radiology, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Ji Hoon Park
- Department of Radiology, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Yoon Jin Lee
- Department of Radiology, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Kyoung Ho Lee
- Department of Radiology, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
| | - Young Hoon Kim
- Department of Radiology, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
| | - Soyeon Ahn
- Division of Statistics, Medical Research Collaborating Center, Seoul National University Bundang Hospital, Seongnam, Korea
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Wang W, Yang Y, Xu Q, Wang S, Zhang L, Yu R, Han J, Cao J. Superficial Flat-Type Early-Stage Gastric Signet Ring Cell Carcinoma in the Atrophic Background Mucosa: Two Case Reports. J Gastrointest Cancer 2023; 54:677-681. [PMID: 35304679 DOI: 10.1007/s12029-022-00812-4] [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] [Accepted: 02/12/2022] [Indexed: 11/24/2022]
Abstract
OBJECTIVES Gastric signet ring cell carcinoma is a rare and highly malignant adenocarcinoma, which is characterized by early metastasis, rapid progression and poor prognosis. Several studies have shown that early-stage gastric signet ring cell carcinoma may have equal or better prognosis than other types of gastric cancer. However, most of the early-stage lesions are difficult to detect by endoscopy. We aim to illustrate the difficulty of early detection of gastric signet ring cell carcinoma with mucosal atrophy. METHODS The endoscopic and pathological features of two female cases were analyzed by upper gastrointestinal white light endoscopy combined with narrow-band imaging and endoscopic biopsy. RESULTS Two female cases were diagnosed with early-stage gastric signet ring cell carcinoma with atrophic background mucosa occurring in the middle and lower part of the stomach. Both lesions less than 2.0 cm in diameter were surgically removed and identified as intramucosal adenocarcinoma. CONCLUSION We can roughly identify the demarcation of the lesion by combining white light endoscopy and narrow-band imaging, and slightly irregular microsurface and microvascular pattern of the lesion were found via magnifying endoscopic observation, but the demarcation can hardly be accurately identified.
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Affiliation(s)
- Wenhua Wang
- Endoscopy Center, Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai, 200120, China
- Endoscopy Center, Anqiu People's Hospital, 159 Xuefu Road, Anqiu, 262100, Shandong, China
| | - Yicheng Yang
- Endoscopy Center, Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai, 200120, China
| | - Qinwei Xu
- Endoscopy Center, Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai, 200120, China
| | - Shunli Wang
- Department of Pathology, Tongji Hospital, Tongji University School of Medicine, 389 Xincun Road, Shanghai, 200065, China
| | - Li Zhang
- Endoscopy Center, Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai, 200120, China
| | - Renfang Yu
- Department of Gastroenterology, Weihai Central Hospital, 3 east Mishan Road, Weihai, 264400, China
| | - Junyi Han
- Endoscopy Center, Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai, 200120, China
| | - Jia Cao
- Endoscopy Center, Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai, 200120, China.
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Zhang F, Chen H, Luo D, Xiong Z, Li X, Yin S, Jin L, Chen S, Peng J, Lian L. Lymphovascular or perineural invasion is associated with lymph node metastasis and survival outcomes in patients with gastric cancer. Cancer Med 2023; 12:9401-9408. [PMID: 36952439 PMCID: PMC10166947 DOI: 10.1002/cam4.5701] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2022] [Revised: 01/11/2023] [Accepted: 02/07/2023] [Indexed: 03/25/2023] Open
Abstract
BACKGROUND Lymphovascular invasion (LVI) and perineural invasion (PNI) are associated with poorer prognosis in several human malignancies, but their significance in gastric cancer (GC) remains to be clearly defined. Our study aimed to investigate the prognostic value of LVI/PNI in patients with curative resected GC. METHODS Records of 1488 patients with stage I--III GC and 3327 patients with stage I-III colorectal cancer (CRC) were reviewed retrospectively, and difference in the incidence of LVI/PNI between GC and CRC was compared. Univariate and multivariate analyses were used to evaluate whether LVI/PNI was an independent risk factor for lymph node metastasis (LNM) and overall survival (OS) in GC. RESULTS Patients with stage I-III GC had a significantly higher incidence of LVI/PNI than patients with stage I-III CRC (50.54% vs. 21.91%, p < 0.001). LVI/PNI was significantly associated with higher CEA, higher CA199, deeper tumor invasion, more lymph node metastasis, and advanced TNM stage in GC ( p < 0.05). Multivariate logistic regression analysis identified LVI/PNI (OR = 2.64, 95%CI: 2.05-3.40, p < 0.001) as an independent risk factor for LNM in GC. The OS rate was significantly lower in the LVI/PNI-positive GC group than that in the LVI/PNI-negative GC group ( p < 0.001). On multivariate Cox regression analysis, LVI/PNI (HR = 1.34, 95%CI: 1.04-1.71, p = 0.023) was an independent prognostic factor for OS in GC. CONCLUSION GC has a high incidence of LVI/PNI, which was closely associated with disease progression. LVI/PNI could serve as an independent risk factor for LNM and the prognosis of patients with curative resected GC. These findings will be helpful in predicting survival outcomes more accurately and establishing individualized treatment plans.
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Affiliation(s)
- Fengxiang Zhang
- Department of Gastrointestinal Surgery, Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Huaxian Chen
- Department of Gastrointestinal Surgery, Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Dandong Luo
- Department of Gastrointestinal Surgery, Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Zhizhong Xiong
- Department of Gastrointestinal Surgery, Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xianzhe Li
- Department of Gastrointestinal Surgery, Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Shi Yin
- Department of Gastrointestinal Surgery, Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Longyang Jin
- Department of Gastrointestinal Surgery, Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Shi Chen
- Department of Gastrointestinal Surgery, Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Junsheng Peng
- Department of Gastrointestinal Surgery, Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Lei Lian
- Department of Gastrointestinal Surgery, Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
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Subasinghe D, Acott N, Mahesh PKB, Sivaganesh S, Munasinghe S, Kumarasinghe MP, Samarasekera DN, Lokuhetty MDS. Human epidermal growth factor receptor-2 gene expression positivity determined by silver in situ hybridization/immunohistochemistry methods and associated factors in a cohort of Sri Lankan patients with gastric adenocarcinoma: a prospective study. J Int Med Res 2023; 51:3000605231154403. [PMID: 36814374 PMCID: PMC9950620 DOI: 10.1177/03000605231154403] [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] [Indexed: 02/24/2023] Open
Abstract
OBJECTIVE Positive human epidermal growth factor 2 (HER2) expression and its predictive clinicopathological features remain unclear in Sri Lankan gastric cancer (GC) patients. Here, we aimed to determine GC HER2 status predictors by analyzing associations between clinicopathological features and HER2 expression using immunohistochemistry (IHC) and silver in situ hybridization (SISH). METHODS During this 4-year prospective study, clinicopathological data were collected from participants in the National Hospital of Sri Lanka. HER2 IHC and SISH were performed using commercial reagents. Using chi-square tests, associations of HER2-IHC/SISH with clinicopathological features were analyzed. RESULTS Overall, 145 GC patients were included, 69 had gastrectomies and 76 had biopsies. Positive HER2 expression by IHC was associated with age <60 years, high T stage (assessed pathologically in resections and radiologically in biopsies), high nuclear grade, tumor necrosis, mitosis >5/high-power field, with additional perineural invasion and lymphovascular invasion in resections. These features, excluding lymphovascular invasion but including male sex, were associated with HER2 expression by SISH. CONCLUSIONS Age <60 years, high nuclear grade, tumor necrosis, and perineural invasion are associated factors of HER2 status. These could be used to triage GC patients for HER2 status testing in limited resource settings where IHC/SISH analysis is costly.
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Affiliation(s)
- Duminda Subasinghe
- Department of Surgery, Faculty of Medicine, University of
Colombo, University Surgical Unit, The National Hospital of Sri Lanka, Colombo,
Sri Lanka,PathWest Laboratory Medicine, Perth, & School of Pathology
and Laboratory Medicine, University of Western Australia, Perth, Australia,Duminda Subasinghe, Department of Surgery,
Faculty of Medicine, University of Colombo, University Surgical Unit, The
National Hospital of Sri Lanka, Colombo 00800, Sri Lanka.
| | - Nathan Acott
- PathWest Laboratory Medicine, Perth, & School of Pathology
and Laboratory Medicine, University of Western Australia, Perth, Australia
| | | | - Sivasuriya Sivaganesh
- Department of Surgery, Faculty of Medicine, University of
Colombo, University Surgical Unit, The National Hospital of Sri Lanka, Colombo,
Sri Lanka
| | - Sithum Munasinghe
- Translational Health Research Institute, Western Sydney
University, Campbelltown Campus, Campbelltown, New South Wales, Australia
| | - Mariyan Priyanthi Kumarasinghe
- PathWest Laboratory Medicine, Perth, & School of Pathology
and Laboratory Medicine, University of Western Australia, Perth, Australia
| | - Dharmabandu Nandaveva Samarasekera
- Department of Surgery, Faculty of Medicine, University of
Colombo, University Surgical Unit, The National Hospital of Sri Lanka, Colombo,
Sri Lanka
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Chen H, Pang Y, Li J, Kang F, Xu W, Meng T, Shang Q, Zhao J, Guan Y, Wu H, Xie F, Wang J, Sun L. Comparison of [ 68Ga]Ga-FAPI and [ 18F]FDG uptake in patients with gastric signet-ring-cell carcinoma: a multicenter retrospective study. Eur Radiol 2023; 33:1329-1341. [PMID: 35976396 DOI: 10.1007/s00330-022-09084-9] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Revised: 07/20/2022] [Accepted: 08/04/2022] [Indexed: 02/03/2023]
Abstract
OBJECTIVE In this study, we investigated the role of [68Ga]Ga-FAPI PET imaging in the detection of primary and metastatic gastric signet-ring-cell carcinoma (GSRCC) and compared with [18F]FDG PET. METHODS This retrospective multicenter analysis included 34 patients with histologically confirmed GSRCCs from four medical centers. The maximum standard uptake value (SUVmax), tumor-to-background ratio (TBR), and diagnostic accuracy were compared between the two modalities. [18F]FDG and [68Ga]Ga-FAPI uptakes were compared by using the Wilcoxon signed-rank test. McNemar's test was used to compare the diagnostic accuracy between the two techniques. RESULTS Data were analyzed from 27 paired PET/CT and 7 paired PET/MRI scans for 34 GSRCC patients (16 men and 18 women) who had a median age of 51 years (range: 25-85 years). [68Ga]Ga-FAPI PET showed higher SUVmax and TBR values than did [18F]FDG PET in the primary tumors (SUVmax: 5.2 vs. 2.2, p = 0.001; TBR: 7.6 vs. 1.3, p < 0.001), involved lymph nodes (SUVmax: 6.8 vs. 2.5, p < 0.001; TBR: 5.8 vs. 1.3, p < 0.001), and bone and visceral metastases (SUVmax: 6.5 vs. 2.4, p < 0.001; TBR: 6.3 vs. 1.3, p < 0.001). In diagnostic performance, [68Ga]Ga-FAPI PET exhibited higher sensitivity than [18F]FDG PET for detecting primary tumors (73% [16/22] vs. 18% [4/22], p < 0.001), local recurrences (100% [7/7] vs. 29% [2/7], p = 0.071), lymph node metastases (77% [59/77] vs. 23% [18/77], p < 0.001), and distant metastases (93% [207/222] vs. 39% [86/222], p < 0.001). CONCLUSION The results from this multicenter retrospective analysis justify the clinical use of [68Ga]Ga-FAPI tracers for GSRCC diagnosis and staging. KEY POINTS • [68Ga]Ga-FAPI PET/CT is a promising imaging modality for the detection of primary and metastatic disease and has implications for TNM staging in GSRCC. • In this multicenter study of 34 patients with GSRCC, [68Ga]Ga-FAPI PET exhibited greater radiotracer uptake, tumor-to-background ratios, and diagnostic accuracy than [18F]FDG PET for detecting primary/recurrent tumors and metastatic lesions.
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Affiliation(s)
- Haojun Chen
- Department of Nuclear Medicine & Minnan PET Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
| | - Yizhen Pang
- Department of Nuclear Medicine & Minnan PET Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
| | - Junpeng Li
- Department of PET Center, Huashan Hospital, Fudan University, Shanghai, China
| | - Fei Kang
- Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Weizhi Xu
- Department of Nuclear Medicine & Minnan PET Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
| | - Tinghua Meng
- Department of Nuclear Medicine & Minnan PET Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
| | - Qihang Shang
- Department of Nuclear Medicine & Minnan PET Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
| | - Jun Zhao
- Department of Nuclear Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Yihui Guan
- Department of PET Center, Huashan Hospital, Fudan University, Shanghai, China
| | - Hua Wu
- Department of Nuclear Medicine & Minnan PET Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
| | - Fang Xie
- Department of PET Center, Huashan Hospital, Fudan University, Shanghai, China.
| | - Jing Wang
- Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
| | - Long Sun
- Department of Nuclear Medicine & Minnan PET Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
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Benites-Goñi H, Palacios-Salas F, Carlin-Ronquillo A, Díaz-Arocutipa C, Piscoya A, Hernández A. Endoscopic submucosal dissection versus surgery for patients with undifferentiated early gastric cancer. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2023; 115:3-9. [PMID: 35297264 DOI: 10.17235/reed.2022.8564/2021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
BACKGROUND AND AIMS endoscopic submucosal dissection (ESD) is the standard treatment for differentiated early gastric cancer (EGC). However, its expanded indication for undifferentiated EGC is controversial. In this study, the efficacy and safety of ESD versus surgery in patients with undifferentiated EGC were compared. METHODS four databases were searched until February 24, 2022, for studies assessing patients with undifferentiated EGC that met an expanded indication for endoscopic resection and who were treated with ESD or surgery. Primary outcomes were all-cause mortality and any recurrence. Secondary outcomes were complete histological resection, local recurrence, metachronous recurrence, synchronous recurrence, distant metastasis, overall complication, and bleeding. All meta-analyses were performed using a random-effects models. Unadjusted (risk ratio [RR]) and adjusted (aRR and hazard ratio [aHR]) estimates with 95 % confidence interval (CI) were calculated. RESULTS seven cohort studies were included (n = 2637). The use of ESD was significantly associated with higher all-cause mortality compared to surgery (RR, 2.17; 95 % CI, 1.24-3.81); adjusted all-cause mortality effects were not significant (aRR, 2.28; 95 % CI, 0.95-5.47 and aHR, 1.97; 95 % CI, 0.85-4.53). ESD was associated with a higher risk of any recurrence using unadjusted (RR, 5.24; 95 % CI, 1.49-18.46) and adjusted (aRR, 7.89; 95 % CI, 1.52-40.95 and aHR, 3.73; 95 % CI, 1.17-11.90) estimates. The risk of local recurrence, synchronous recurrence and bleeding were significantly higher for ESD versus surgery. No significant differences were found for other secondary outcomes. CONCLUSIONS although ESD is associated with a higher risk of any recurrence, adjusted all-cause mortality is similar during follow-up. Overall complications were similar between ESD and surgery.
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22
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Tian HK, Zhang Z, Ning ZK, Liu J, Liu ZT, Huang HY, Zong Z, Li H. Clinicopathological characteristics and prognosis of gastric signet ring cell carcinoma. World J Clin Cases 2022; 10:10451-10466. [PMID: 36312481 PMCID: PMC9602248 DOI: 10.12998/wjcc.v10.i29.10451] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2022] [Revised: 07/21/2022] [Accepted: 08/31/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND The clinicopathological features and prognosis of gastric signet ring cell carcinoma (GSRC) remain controversial, particularly with regard to sensitivity to postoperative adjuvant therapy.
AIM To compare the pathological features of GSRC with those of gastric adenocarcinoma of different degrees of differentiation and the differences in survival prognosis between the different disease processes.
METHODS By screening gastric cancer patients from 2010 to 2015 in the database of Surveillance, Epidemiology and End Results, and collecting the clinicopathological and prognostic data of gastric cancer patients who underwent surgery from January 2014 to December 2016 in the Second Affiliated Hospital of Nanchang University, we analyzed the general pathological characteristics of GSRC by the chi-square test. Univariate and multivariate analyses were conducted to compare the factors affecting the survival and prognosis of early and advanced gastric adenocarcinoma. The Kaplan-Meier curves were plotted to reveal the survival difference between early and advanced GSRC and different differentiated types of gastric adenocarcinoma. The prognosis model of advanced GSRC was established with R software, and the area under curve (AUC) and C-index were used to assess the accuracy of the model.
RESULTS Analysis of pathological features revealed that signet ring-cell carcinoma (SRC) was more frequently seen in younger (< 60 years), female, and White patients compared to non-SRC patients. SRC was less commonly associated with early gastric cancer (EGC) (23.60% vs 39.10%), lower N0 (38.61% vs 61.03%), and larger tumour sizes > 5 cm (31.15% vs 27.10%) compared to the differentiated type, while the opposite was true compared to the undifferentiated type. Survival prognostic analysis found no significant difference in the prognosis of SRC patients among EGC patients. In contrast, among advanced gastric cancer (AGC) patients, the prognosis of SRC patients was correlated with age, race, tumour size, AJCC stage, T-stage, and postoperative adjuvant therapy. The predictive model showed that the 3-year AUC was 0.787, 5-year AUC was 0.806, and C-index was 0.766. Compared to non-SRC patients, patients with SRC had a better prognosis in EGC [hazard ratio (HR): 0.626, 95% confidence interval (CI): 0.427-0.919, P < 0.05] and a worse prognosis in AGC (HR: 1.139, 95%CI: 1.030-1.258, P < 0.05). When non-SRC was divided into differentiated and undifferentiated types for comparison, it was found that in EGC, SRC had a better prognosis than differentiated and undifferentiated types, while there was no significant difference between differentiated and undifferentiated types. In AGC, there was no significant difference in prognosis between SRC and undifferentiated types, both of which were worse than differentiated types. A prognostic analysis of postoperative adjuvant therapy for SRC in patients with AGC revealed that adjuvant postoperative radiotherapy or chemotherapy significantly improved patient survival (34.6% and 36.2% vs 18.6%, P < 0.05).
CONCLUSION The prognosis of SRC is better than that of undifferentiated type, especially in EGC, and its prognosis is even better than that of differentiated type. SRC patients can benefit from early detection, surgical resection, and aggressive adjuvant therapy.
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Affiliation(s)
- Hua-Kai Tian
- Department of General Surgery, First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Zuo Zhang
- Department of Obstetrics and Gynecology, Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Zhi-Kun Ning
- Department of Day Ward, First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Jiang Liu
- Department of Gastrointestinal Surgery, Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Zi-Tao Liu
- Department of Gastrointestinal Surgery, Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Hao-Yu Huang
- Department of Gastrointestinal Surgery, Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Zhen Zong
- Department of Gastrointestinal Surgery, Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Hui Li
- Department of Rheumatology and Immunology, First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
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Dong Z, Zhang Y, Geng H, Ni B, Xia X, Zhu C, Liu J, Zhang Z. Development and validation of two nomograms for predicting overall survival and cancer-specific survival in gastric cancer patients with liver metastases: A retrospective cohort study from SEER database. Transl Oncol 2022; 24:101480. [PMID: 35868142 PMCID: PMC9304879 DOI: 10.1016/j.tranon.2022.101480] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Revised: 06/04/2022] [Accepted: 07/04/2022] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND Gastric cancer is heterogeneous and aggressive, especially with liver metastasis. This study aims to develop two nomograms to predict the overall survival (OS) and cancer-specific survival (CSS) of gastric cancer with liver metastasis (GCLM) patients. METHODS From January 2000 to December 2018, a total of 1936 GCLM patients were selected from the Surveillance, Epidemiology, and End Results Program (SEER) database. They were further divided into a training cohort and a validation cohort, with the OS and CSS serving as the study's endpoints. The correlation analyses were used to determine the relationship between the variables. The univariate and multivariate Cox analyses were used to confirm the independent prognostic factors. To discriminate and calibrate the nomogram, calibration curves and the area under the time-dependent receiver operating characteristic curve (time-dependent AUC) were used. DCA curves were used to examine the accuracy and clinical benefits. The clinical utility of the nomogram and the AJCC Stage System was compared using net reclassification improvement (NRI) and integrated differentiation improvement (IDI) (IDI). Finally, the nomogram and the AJCC Stage System risk stratifications were compared. RESULTS There was no collinearity among the variables that were screened. The results of multivariate Cox regression analysis showed that six variables (bone metastasis, lung metastasis, surgery, chemotherapy, grade, age) and five variables (lung metastasis, surgery, chemotherapy, grade, N stage) were identified to establish the nomogram for OS and CSS, respectively. The calibration curves, time-dependent AUC curves, and DCA revealed that both nomograms had pleasant predictive power. Furthermore, NRI and IDI confirmed that the nomogram outperformed the AJCC Stage System. CONCLUSION Both nomograms had satisfactory accuracy and were validated to assist clinicians in evaluating the prognosis of GCLM patients.
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Affiliation(s)
- Zhongyi Dong
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, No.1630 East Road, Pudong New Area, Shanghai 200127, China
| | - Yeqian Zhang
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, No.1630 East Road, Pudong New Area, Shanghai 200127, China
| | - Haigang Geng
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, No.1630 East Road, Pudong New Area, Shanghai 200127, China
| | - Bo Ni
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, No.1630 East Road, Pudong New Area, Shanghai 200127, China
| | - Xiang Xia
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, No.1630 East Road, Pudong New Area, Shanghai 200127, China
| | - Chunchao Zhu
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, No.1630 East Road, Pudong New Area, Shanghai 200127, China
| | - Jiahua Liu
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, No.1630 East Road, Pudong New Area, Shanghai 200127, China.
| | - Zizhen Zhang
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, No.1630 East Road, Pudong New Area, Shanghai 200127, China.
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Predicting Overall Survival in Patients with Nonmetastatic Gastric Signet Ring Cell Carcinoma: A Machine Learning Approach. COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE 2022; 2022:4862376. [PMID: 36148015 PMCID: PMC9489421 DOI: 10.1155/2022/4862376] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/20/2022] [Revised: 08/16/2022] [Accepted: 08/24/2022] [Indexed: 11/30/2022]
Abstract
Background and Aims Accurate prediction is essential for the survival of patients with nonmetastatic gastric signet ring cell carcinoma (GSRC) and medical decision-making. Current models rely on prespecified variables, limiting their performance and not being suitable for individual patients. Our study is aimed at developing a more precise model for predicting 1-, 3-, and 5-year overall survival (OS) in patients with nonmetastatic GSRC based on a machine learning approach. Methods We selected 2127 GSRC patients diagnosed from 2004 to 2014 from the Surveillance, Epidemiology, and End Results (SEER) database and then randomly partitioned them into a training and validation cohort. We compared the performance of several machine learning-based models and finally chose the eXtreme gradient boosting (XGBoost) model as the optimal method to predict the OS in patients with nonmetastatic GSRC. The model was assessed using the receiver operating characteristic curve (ROC). Results In the training cohort, for predicting OS rates at 1-, 3-, and 5-year, the AUCs of the XGBoost model were 0.842, 0.831, and 0.838, respectively, while in the testing cohort, the AUCs of 1-, 3-, and 5-year OS rates were 0.749, 0.823, and 0.829, respectively. Besides, the XGBoost model also performed better when compared with the American Joint Committee on Cancer (AJCC) stage. The performance for this model was stably maintained when stratified by age and ethnicity. Conclusion The XGBoost-based model accurately predicts the 1-, 3-, and 5-year OS in patients with nonmetastatic GSRC. Machine learning is a promising way to predict the survival outcomes of tumor patients.
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Yang Y, Akashi Y, Shimomura O, Tateno H, Saito S, Hiemori K, Miyazaki Y, Furuta T, Kitaguchi D, Kuroda Y, Pakavarin L, Oda T. Glycan expression profile of signet ring cell gastric cancer cells and potential applicability of rBC2LCN-targeted lectin drug conjugate therapy. Gastric Cancer 2022; 25:896-905. [PMID: 35715659 DOI: 10.1007/s10120-022-01312-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Accepted: 05/25/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND Signet ring cell carcinoma (SRC) is a distinct subtype of gastric cancer (GC); however, the specific characteristics of cancer cell surface glycans and glycosylation remain unclear. In this study, we investigated SRC-specific glycans using lectin microarray and evaluated the potential applicability of a glycan-targeting therapy. METHODS SRC cell lines (NUGC-4 and KATO-III) and non-SRC (NSRC) cell lines (NCI-N87, SNU-1, and MKN-45) were subjected to lectin microarray analysis to identify the SRC-specific glycans. Additionally, we performed immunohistochemical lectin staining and evaluated the anti-tumor effects of lectin drug conjugates (LDCs) using high-affinity lectins for SRC. RESULTS Among the 96 lectins tested, 11 high-affinity and 8 low-affinity lectins were identified for SRC. Glycan-binding motifs varied in the high-affinity lectins, but 5 (62.5%) low-affinity lectins bound the same glycan structure, α2-6-linked sialic acids. The ratio of signal intensity in SRC to NSRC (SRC/NSRC) was highest in the rBC2LCN lectin (1.930-fold), followed by the BPL lectin (1.786-fold). rBC2LCN lectin showed high affinity for both SRC cell lines and one of the three NSRC cell lines (NCI-N87). The therapeutic effects of the LDC, rBC2LCN-PE38 (rBC2LCN, and Pseudomonas exotoxin A), showed cytocidal effects in vitro and tumor regression in in vivo mouse xenograft models. CONCLUSION We reported specific glycan profiles in SRC cells, showing reduced α2-6-linked sialic acids. Additionally, we found a targeted therapy using rBC2LCN lectin might be applicable as an alternative treatment option for patients with SRC.
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Affiliation(s)
- Yu Yang
- Department of Gastrointestinal and Hepato-Billiary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Yoshimasa Akashi
- Department of Gastrointestinal and Hepato-Billiary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.
| | - Osamu Shimomura
- Department of Gastrointestinal and Hepato-Billiary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Hiroaki Tateno
- Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki, Japan
| | - Sayoko Saito
- Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki, Japan
| | - Keiko Hiemori
- Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki, Japan
| | - Yoshihiro Miyazaki
- Department of Gastrointestinal and Hepato-Billiary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Tomoaki Furuta
- Department of Gastrointestinal and Hepato-Billiary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Daichi Kitaguchi
- Department of Gastrointestinal and Hepato-Billiary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Yukihito Kuroda
- Department of Gastrointestinal and Hepato-Billiary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Louphrasitthiphol Pakavarin
- Department of Gastrointestinal and Hepato-Billiary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Tatsuya Oda
- Department of Gastrointestinal and Hepato-Billiary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan
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Drubay V, Nuytens F, Renaud F, Adenis A, Eveno C, Piessen G. Poorly cohesive cells gastric carcinoma including signet-ring cell cancer: Updated review of definition, classification and therapeutic management. World J Gastrointest Oncol 2022; 14:1406-1428. [PMID: 36160745 PMCID: PMC9412924 DOI: 10.4251/wjgo.v14.i8.1406] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Revised: 05/08/2022] [Accepted: 07/17/2022] [Indexed: 02/05/2023] Open
Abstract
While the incidence of gastric cancer (GC) in general has decreased worldwide in recent decades, the incidence of diffuse cancer historically comprising poorly cohesive cells-GC (PCC-GC) and including signet ring cell cancer is rising. Literature concerning PCC-GC is scarce and unclear, mostly due to a large variety of historically used definitions and classifications. Compared to other histological subtypes of GC, PCC-GC is nevertheless characterized by a distinct set of epidemiological, histological and clinical features which require a specific diagnostic and therapeutic approach. The aim of this review was to provide an update on the definition, classification and therapeutic strategies of PCC-GC. We focus on the updated histological definition of PCC-GC, along with its implications on future treatment strategies and study design. Also, specific considerations in the diagnostic management are discussed. Finally, the impact of some recent developments in the therapeutic management of GC in general such as the recently validated taxane-based regimens (5-Fluorouracil, leucovorin, oxaliplatin and docetaxel), the use of hyperthermic intraperitoneal chemotherapy as well as pressurized intraperitoneal aerosol chemotherapy and targeted therapy have been reviewed in depth for their relative importance for PCC-GC in particular.
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Affiliation(s)
- Vincent Drubay
- Department of Digestive and Oncological Surgery, University Lille, Claude Huriez University Hospital, Lille 59000, France
- Department of Digestive Surgery, Cambrai Hospital Center and Sainte Marie, Group of Hospitals of The Catholic Institute of Lille, Cambrai 59400, France
| | - Frederiek Nuytens
- Department of Digestive and Oncological Surgery, University Lille, Claude Huriez University Hospital, Lille 59000, France
- Department of Digestive and Hepatobiliary/Pancreatic Surgery, AZ Groeninge Hospital, Kortrijk 8500, Belgium
| | - Florence Renaud
- Department of Pathology, University Lille Hospital, Lille 59000, France
- CNRS, Inserm, UMR9020-U1277-CANTHER-Cancer, University Lille, CHU Lille, Lille 59000, France
- FREGAT Network, Claude Huriez University Hospital, Lille 59000, France
| | - Antoine Adenis
- FREGAT Network, Claude Huriez University Hospital, Lille 59000, France
- Department of Medical Oncology, Montpellier Cancer Institute, Monpellier 34000, France
- IRCM, Inserm, University of Monpellier, Monpellier 34000, France
| | - Clarisse Eveno
- Department of Digestive and Oncological Surgery, University Lille, Claude Huriez University Hospital, Lille 59000, France
- CNRS, Inserm, UMR9020-U1277-CANTHER-Cancer, University Lille, CHU Lille, Lille 59000, France
- FREGAT Network, Claude Huriez University Hospital, Lille 59000, France
| | - Guillaume Piessen
- Department of Digestive and Oncological Surgery, University Lille, Claude Huriez University Hospital, Lille 59000, France
- CNRS, Inserm, UMR9020-U1277-CANTHER-Cancer, University Lille, CHU Lille, Lille 59000, France
- FREGAT Network, Claude Huriez University Hospital, Lille 59000, France
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Guo Y, Wang Q, Tian Q, Bo C, Li N, Zhang S, Li P. Clinicopathological Features and Prognostic-Related Risk Factors of Gastric Signet Ring Cell Carcinoma: A Meta-Analysis. COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE 2022; 2022:3473445. [PMID: 36035278 PMCID: PMC9410921 DOI: 10.1155/2022/3473445] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Revised: 07/06/2022] [Accepted: 07/17/2022] [Indexed: 11/23/2022]
Abstract
Background Gastric signet ring cell carcinoma (SRCC) has shown a growth growing trend worldwide, but its clinicopathological features and prognostic-related risk factors have not been systematically studied. This systematic review was devoted to this. Method PubMed, Embase, Cochrane Library, and Web of Science databases were retrieved, and retrospective cohort studies comparing clinicopathological features and related risk factors in SRCC patients were included. Results In SRCC patient population, males were more than females (male, OR = 1.38, 95% CI: 1.20-1.60); N3 patients were more than N0-2 patients (N0-2, OR = 3.19, 95% CI: 1.98-5.15); M1 patients were more than M0 patients (M0, OR = 3.30, 95% CI: 1.88-5.80); patients with tumor > 5 cm were more than those with tumor (≤5 cm, OR = 7.36, 95% CI: 1.33-40.60). Patients with age < 60 years (age ≥ 60 years, OR = 1.03, 95% CI: 1.01-1.05), lymphatic vessel invasion (no, OR = 1.74, 95% CI: 1.03-2.45), T2 (T1, OR = 1.17, 95% CI: 1.07-1.28) and T4 (T1, OR = 2.55, 95% CI: 2.30-2.81) stages, and N1 (N0, OR = 1.73, 95% CI: 1.08-2.38), N2 (N0, OR = 2.24, 95% CI: 1.12-3.36), and N3 (N0, OR = 3.45, 95% CI: 1.58-5.32) stages had higher hazard ratio (HR). Conclusion SRCC may occur frequently in male. Age, lymphatic vessel invasion, TN, and M stage may be risk factors for poor prognoses of SRCC patients.
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Affiliation(s)
- Ying Guo
- Department of Oncology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China
| | - Qian Wang
- Department of Oncology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China
| | - Qing Tian
- Thoracic Surgery Department, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China
| | - Changwen Bo
- Department of Oncology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China
| | - Na Li
- Department of Oncology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China
| | - Sujing Zhang
- Department of Oncology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China
| | - Peishun Li
- Department of Oncology, Tengzhou Central People's Hospital, Tengzhou, Shandong 277500, China
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Zaafouri H, Jouini R, Khedhiri N, Khanchel F, Cherif M, Mesbahi M, Daghmouri A, Mahmoudi W, Akremi S, Sabbah M, Benzarti Y, Hadded D, Gargouri D, Bader MB, Maamer AB. Comparison between signet-ring cell carcinoma and non-signet-ring cell carcinoma of the stomach: clinicopathological parameters, epidemiological data, outcome, and prognosis-a cohort study of 123 patients from a non-endemic country. World J Surg Oncol 2022; 20:238. [PMID: 35858903 PMCID: PMC9297662 DOI: 10.1186/s12957-022-02699-8] [Citation(s) in RCA: 9] [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: 02/01/2022] [Accepted: 06/29/2022] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Signet-ring cell carcinoma of the stomach (SRCC) is a particular gastric cancer entity. Its incidence is increasing. Its diagnosis is pathological; it corresponds to adenocarcinoma with a majority of signet-ring cells component (> 50%). These histological features give it its aggressiveness characteristics. This has repercussions on the prognostic level and implications for the alternatives of therapy, especially since some authors suggest a potential chemoresistance. This survey aimed to identify the epidemiological, pathological, therapeutic, and prognostic characteristics of SRCC as a separate disease entity. METHODS This was a retrospective study of 123 patients admitted for gastric adenocarcinoma to Habib Thameur Hospital in Tunis over 11 years from January 2006 to December 2016. A comparative study was performed between 2 groups: the SRCC group with 62 patients and the non-SRCC (non-signet-ring cell carcinoma of the stomach) with 61 patients. RESULTS The prevalence of SRCC in our series was 50%. SRCC affected significantly younger patients (55 vs 62 years; p = 0.004). The infiltrative character was more common in SRCC tumors (30.6 vs 14.8%; p = 0.060), whereas the budding character was more often noted in non-SRCC tumors (78.7 vs 58.1%; p = 0.039). There was no significant difference in tumor localization between both groups. Linitis plastica was noted in 14 patients with SRCC against a single patient with non-SRCC (p = 0.001). The tumor size was more important in the non-SRCC group (6.84 vs 6.39 cm; p = 0.551). Peritoneal carcinomatosis was noted in 4.3% of cases in the SRCC group versus 2.2% of cases in the NSRCC group (p = 0.570). Total gastrectomy was more often performed in the SRCC group (87 vs 56%; p = 0.001). Resection was more often curative in the non-SRCC group (84.4 vs 78.3%; p = 0.063). Postoperative chemotherapy was more commonly indicated in the SRCC group (67.4 vs 53.3%; p = 0.339). Tumor recurrence was more common in the non-SRCC group (35.7 vs 32%; p = 0.776). The most common type of recurrence was peritoneal carcinomatosis in the SRCC group (62.5%) and hepatic metastasis in the non-SRCC group (60%; p = 0.096). The overall 5-year survival in the SRCC group was lower than in the non-SRCC group, with no statistically significant difference (47.1 vs 51.5%; p = 0.715). The overall survival was more important for SRCC in early cancer (100 vs 80%; p = 0.408), whereas it was higher for non-SRCC in advanced cancer (48.1 vs 41.9%; p = 0.635). CONCLUSION Apart from its epidemiological and pathological features, SRCC seems to have a worse prognosis. Indeed, it is diagnosed at a more advanced stage and has a worse prognosis in advanced cancer than non-SRCC. It is therefore to be considered as a particular entity of gastric adenocarcinoma requiring a specific therapeutic protocol where the place of chemotherapy remains to be more investigated.
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Affiliation(s)
- Haithem Zaafouri
- Department of General Surgery, Habib Thameur Hospital, Tunis, Tunisia.
| | - Raja Jouini
- Department of Cytopathology, Habib Thameur Hospital, Tunis, Tunisia
| | - Nizar Khedhiri
- Department of General Surgery, Habib Thameur Hospital, Tunis, Tunisia
| | - Fatma Khanchel
- Department of Cytopathology, Habib Thameur Hospital, Tunis, Tunisia
| | - Mona Cherif
- Department of General Surgery, Habib Thameur Hospital, Tunis, Tunisia
| | - Meryam Mesbahi
- Department of General Surgery, Habib Thameur Hospital, Tunis, Tunisia
| | - Aziz Daghmouri
- Department of Anesthesiology, Habib Thameur Hospital, Tunis, Tunisia
| | - Wiem Mahmoudi
- Department of General Surgery, Habib Thameur Hospital, Tunis, Tunisia
| | - Soumaya Akremi
- Department of Anesthesiology, Habib Thameur Hospital, Tunis, Tunisia
| | - Meriam Sabbah
- Department of Gastroenterology, Habib Thameur Hospital, Tunis, Tunisia
| | - Yazid Benzarti
- Department of General Surgery, Habib Thameur Hospital, Tunis, Tunisia
| | - Dhafer Hadded
- Department of General Surgery, Habib Thameur Hospital, Tunis, Tunisia
| | - Dalila Gargouri
- Department of Gastroenterology, Habib Thameur Hospital, Tunis, Tunisia
| | - Mourad Ben Bader
- Department of General Surgery, Habib Thameur Hospital, Tunis, Tunisia
| | - Anis Ben Maamer
- Department of General Surgery, Habib Thameur Hospital, Tunis, Tunisia
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Puccini A, Poorman K, Catalano F, Seeber A, Goldberg RM, Salem ME, Shields AF, Berger MD, Battaglin F, Tokunaga R, Naseem M, Zhang W, Philip PA, Marshall JL, Korn WM, Lenz HJ. Molecular profiling of signet-ring-cell carcinoma (SRCC) from the stomach and colon reveals potential new therapeutic targets. Oncogene 2022; 41:3455-3460. [PMID: 35618879 DOI: 10.1038/s41388-022-02350-6] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2021] [Revised: 05/04/2022] [Accepted: 05/06/2022] [Indexed: 11/09/2022]
Abstract
Signet ring cell carcinoma (SRCC) is rare: about 10% of gastric cancer (GC) and 1% of colorectal cancer (CRC). SRCC is associated with poor prognosis, however the underlying molecular characteristics are unknown. SRCCs were analyzed using NGS, immunohistochemistry, and in situ hybridization. Tumor mutational burden (TMB) was calculated based on somatic nonsynonymous missense mutations, and microsatellite instability (MSI) was evaluated by NGS of known MSI loci. A total of 8500 CRC and 1100 GC were screened. Seventy-six SRCC were identified from the CRC cohort (<1%) and 98 from the GC cohort (9%). The most frequently mutated genes in CRC-SRCC were TP53 (47%), ARID1A (26%), APC (25%); in GC-SRCC were TP53 (42%), ARID1A (27%), CDH1 (11%). When compared to non-SRCC histology (N = 3522), CRC-SRCC (N = 37) more frequently had mutations in BRCA1 (11% vs 1%, P < 0.001) and less frequently mutations in APC (19% vs 78%, P < 0.001), KRAS (22% vs 51%, P = 0.001) and TP53 (47% vs 73%, P = 0.001). Among the GC cohort, SRCC (N = 54) had a higher frequency of mutations in CDH1, BAP1, and ERBB2, compared to non-SRCC (N = 540). Our data suggest that SRCCs harbor a similar molecular profile, regardless of the tumor location. Tailored therapy may become available for these patients.
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Affiliation(s)
- Alberto Puccini
- Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.,University of Genoa, Ospedale Policlinico San Martino-IRCCS, Genova, Italy
| | | | - Fabio Catalano
- University of Genoa, Ospedale Policlinico San Martino-IRCCS, Genova, Italy
| | - Andreas Seeber
- Department of Hematology and Oncology, Comprehensive Cancer Center Innsbruck, Innsbruck Medical University, Innsbruck, Austria
| | | | | | - Anthony F Shields
- Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA
| | - Martin D Berger
- Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Francesca Battaglin
- Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Ryuma Tokunaga
- Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Madiha Naseem
- Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Wu Zhang
- Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Philip A Philip
- Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA
| | - John L Marshall
- Ruesch Center for The Cure of Gastrointestinal Cancers, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA
| | | | - Heinz-Josef Lenz
- Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
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Ma J, Meng Y, Zhou X, Guo L, Fu W. The Prognostic Significance and Gene Expression Characteristics of Gastric Signet-Ring Cell Carcinoma: A Study Based on the SEER and TCGA Databases. Front Surg 2022; 9:819018. [PMID: 35372476 PMCID: PMC8967986 DOI: 10.3389/fsurg.2022.819018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2021] [Accepted: 02/07/2022] [Indexed: 11/13/2022] Open
Abstract
PurposeThis study is based on the Surveillance, Epidemiology, and End Results (SEER) program to explore the prognostic differences between signet-ring cell carcinoma (SRC) and intestinal-type gastric carcinoma (ITGC). This study is also based on gene sequencing data from The Cancer Genome Atlas (TCGA) to identify unique genetic contributions to the prognostic differences between the two subtypes of gastric cancer.Patients and MethodsThe clinical data were based on the SEER database from 2004 to 2015. Kaplan–Meier (KM) curves were used to compare 5-year overall survival (OS), and Cox regression was used for univariate and multivariate analyses. Gene expression profiles were obtained from TCGA database, and differentially expressed genes (DEGs) were screened. Functional enrichment analysis, protein interaction and survival analysis will be further carried out. Genes of interest were verified by the Human Protein Atlas, immunohistochemistry, and encyclopedia of Cancer Cell Lines (CCLE). The relationship between genes of interest and immune cell infiltration was also analyzed by Tumor Immune Estimation Resource (TIMER).ResultsCompared with ITGC patients, SRC patients were more likely to be female, tended to be younger, and have a greater tumor distribution in the middle and lower stomach (p < 0.01). SRCs showed a significantly better prognosis than ITGCs (p < 0.01) in early gastric cancer (EGC), while the prognosis of SRCs was significantly worse than ITGCs (p < 0.05) in advanced gastric cancer (AGC). A total of 256 DEGs were screened in SRCs compared to ITGCs, and the enrichment analysis and protein interactions revealed that differential genes were mainly related to extracellular matrix organization. Thrombospondin1 (THBS1) and serpin peptidase inhibitor, clade E, member 1 (SERPINE1) are significantly differentially expressed between SRC and ITGC, which has been preliminarily verified by immunohistochemistry and open-source databases. THBS1 and SERPINE1 are also associated with multiple immune cell infiltrates in gastric cancer.ConclusionsThere were significant differences in the clinicopathological features and prognosis between SRC and ITGC. These results suggest that SRC and ITGC may be two distinct types of tumors with different pathogeneses. We found many codifferentially expressed genes and important pathways between SRC and ITGC. THBS1 and SERPINE1 were significantly differentially expressed in the two types of gastric cancer, and may have potentially important functions.
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Affiliation(s)
- Junren Ma
- Department of General Surgery, Peking University Third Hospital, Beijing, China
| | - Yan Meng
- Department of General Surgery, Peking University Third Hospital, Beijing, China
| | - Xin Zhou
- Department of General Surgery, Peking University Third Hospital, Beijing, China
- Peking University Third Hospital Cancer Center, Beijing, China
- *Correspondence: Xin Zhou
| | - Limei Guo
- Department of Pathology, Peking University Third Hospital, Beijing, China
- Limei Guo
| | - Wei Fu
- Department of General Surgery, Peking University Third Hospital, Beijing, China
- Peking University Third Hospital Cancer Center, Beijing, China
- Wei Fu
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Weng Q, Li Z, Xie Y, Guo J, Zhang Y, Ye G. Characteristics and Predictors of Long-Time Survivors in Non-Metastatic Gastric Signet Ring Cell Carcinoma: A Large Population-Based Study. Int J Gen Med 2022; 15:3133-3142. [PMID: 35342298 PMCID: PMC8942124 DOI: 10.2147/ijgm.s350448] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Accepted: 03/07/2022] [Indexed: 11/23/2022] Open
Abstract
Objective Gastric signet ring cell carcinoma (SRCC) is a distinct entity with a relatively poor prognosis. This study analyzed the clinicopathological characteristics of long-time survivors (LTSs) and identified independent predictors of long-term survival (LTS) in non-metastatic gastric SRCC. Methods Data from 3906 patients with non-metastatic gastric SRCC were retrieved from Surveillance, Epidemiology and End Results according to the inclusion and exclusion criteria. Patients were randomly divided into training and validation cohorts. Predictors of LTS in the training cohort were identified by multivariate logistic regression. A nomogram-based predictive model for LTS was constructed in non-metastatic gastric SRCC. Results There were 800 patients who survived for >5 years and were defined as TLSs. Young age, other race (not black or white population), female gender, married status, small tumor size, low tumor infiltration, and negative lymph node involvement were independent predictors of LTS in non-metastatic gastric SRCC. These seven variables were incorporated into a nomogram model for predicting LTS. The calibration curve showed good consistency between observed and predicted probability of LTS, and the receiver operating characteristic curve showed acceptable discriminative capacity in the training and validation cohorts. Conclusion This study provides an overview of the features of patients with non-metastatic gastric SRCC. Age, race, sex, marital status, tumor size, tumor infiltration, and lymph node involvement were identified as independent predictors of LTS.
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Affiliation(s)
- Qiuyan Weng
- Department of Neurology, The Affiliated Hospital of Medical School, Ningbo University, Ningbo, Zhejiang, People’s Republic of China
| | - Zhe Li
- Department of Gastroenterology, The Affiliated Hospital of Medical School, Ningbo University, Ningbo, Zhejiang, People’s Republic of China
- Institute of Digestive Diseases, Ningbo University, Ningbo, Zhejiang, People’s Republic of China
| | - Yaoyao Xie
- Department of Biochemistry and Molecular Biology and Zhejiang Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, Zhejiang, People’s Republic of China
| | - Junming Guo
- Department of Gastroenterology, The Affiliated Hospital of Medical School, Ningbo University, Ningbo, Zhejiang, People’s Republic of China
- Institute of Digestive Diseases, Ningbo University, Ningbo, Zhejiang, People’s Republic of China
- Department of Biochemistry and Molecular Biology and Zhejiang Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, Zhejiang, People’s Republic of China
| | - Yong Zhang
- Department of Trauma Orthopedics, Ningbo No. 6 Hospital, Ningbo, Zhejiang, People’s Republic of China
- Yong Zhang, Department of Trauma Orthopedics, Ningbo No. 6 Hospital, Ningbo, 315000, Zhejiang, People’s Republic of China, Email
| | - Guoliang Ye
- Department of Gastroenterology, The Affiliated Hospital of Medical School, Ningbo University, Ningbo, Zhejiang, People’s Republic of China
- Institute of Digestive Diseases, Ningbo University, Ningbo, Zhejiang, People’s Republic of China
- Correspondence: Guoliang Ye, Department of Gastroenterology, The Affiliated Hospital of Medical School, Ningbo University, Ningbo, 315020, People’s Republic of China, Tel +86-574-87035171, Fax +86-574-87380487, Email
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Prognostic Value of Gastric Signet Ring Cell Carcinoma: a Population-Based Propensity Score-Matched Analysis. Indian J Surg 2022. [DOI: 10.1007/s12262-021-02802-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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Nakamura K, Eto K, Iwagami S, Ogawa K, Sawayama H, Ishimoto T, Iwatsuki M, Baba Y, Miyamoto Y, Yoshida N, Baba H. Clinicopathological characteristics and prognosis of poorly cohesive cell subtype of gastric cancer. Int J Clin Oncol 2022; 27:512-519. [PMID: 35084597 DOI: 10.1007/s10147-021-02069-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Accepted: 10/31/2021] [Indexed: 11/30/2022]
Abstract
BACKGROUND The new World Health Organization (WHO) classification of gastric cancer includes a histological subtype of poorly cohesive carcinoma (PCC), which includes signet-ring cell (SRC) phenotype. We aimed to examine the concordance between preoperative clinical and postoperative histological diagnoses according to the 2010 WHO histological subtypes and to compare the prognoses of these subtypes. METHODS The study cohort comprised 665 patients who underwent gastrectomy from 2005 to 2019. Histological subtypes were classified into PCC-NOS (non-signet ring cell subtype), SRC, and non-PCC, which were defined by the predominant component in accordance with the 2010 WHO classification of gastric cancer. The concordance of clinical and pathological diagnosis was examined and clinicopathological characteristics and survival outcome of the three subtypes compared. RESULTS The cancers of 443 patients (66.7%) were classified as non-PCC, of 112 patients (16.8%) as PCC-NOS, and of 110 patients (16.5%) as SRC predominant subtypes. Significant differences in sex, age, tumor location, size, macroscopic type, and pathological TNM category (all P<0.05) were found. The concordance rate of preoperative and postoperative histological subtypes was significantly lower for poorly cohesive than other subtypes (P<0.0001). Preoperative stage tended to be underestimated for PCC-NOS subtype and these patients had poorer overall survival than those with the other two subtypes (P=0.005). Multivariate logistic regression analysis of overall survival showed that WHO histological subtype (PCC-NOS vs. non-PCC/SRC, HR: 1.64, 95% CI: 1.18-2.29, P=0.0034) was a significant independent prognostic factor. CONCLUSION Our results suggest that poorly cohesive carcinoma subtypes have different biological characteristics and prognoses.
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Affiliation(s)
- Kenichi Nakamura
- Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
| | - Kojiro Eto
- Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Shiro Iwagami
- Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Katsuhiro Ogawa
- Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Hiroshi Sawayama
- Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Takatsugu Ishimoto
- Gastrointestinal Cancer Biology, International Research Center for Medical Sciences, Kumamoto University, Kumamoto, 860-8556, Japan
| | - Masaaki Iwatsuki
- Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Yoshifumi Baba
- Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Yuji Miyamoto
- Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Naoya Yoshida
- Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
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Hsieh HL, Yu MC, Cheng LC, Yeh TS, Tsai MM. Molecular mechanism of therapeutic approaches for human gastric cancer stem cells. World J Stem Cells 2022; 14:76-91. [PMID: 35126829 PMCID: PMC8788185 DOI: 10.4252/wjsc.v14.i1.76] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2021] [Revised: 05/15/2021] [Accepted: 12/21/2021] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer (GC) is a primary cause of cancer-related mortality worldwide, and even after therapeutic gastrectomy, survival rates remain poor. The presence of gastric cancer stem cells (GCSCs) is thought to be the major reason for resistance to anticancer treatment (chemotherapy or radiotherapy), and for the development of tumor recurrence, epithelial-mesenchymal transition, and metastases. Additionally, GCSCs have the capacity for self-renewal, differentiation, and tumor initiation. They also synthesize antiapoptotic factors, demonstrate higher performance of drug efflux pumps, and display cell plasticity abilities. Moreover, the tumor microenvironment (TME; tumor niche) that surrounds GCSCs contains secreted growth factors and supports angiogenesis and is thus responsible for the maintenance of the growing tumor. However, the genesis of GCSCs is unclear and exploration of the source of GCSCs is essential. In this review, we provide up-to-date information about GCSC-surface/intracellular markers and GCSC-mediated pathways and their role in tumor development. This information will support improved diagnosis, novel therapeutic approaches, and better prognosis using GCSC-targeting agents as a potentially effective treatment choice following surgical resection or in combination with chemotherapy and radiotherapy. To date, most anti-GCSC blockers when used alone have been reported as unsatisfactory anticancer agents. However, when used in combination with adjuvant therapy, treatment can improve. By providing insights into the molecular mechanisms of GCSCs associated with tumors in GC, the aim is to optimize anti-GCSCs molecular approaches for GC therapy in combination with chemotherapy, radiotherapy, or other adjuvant treatment.
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Affiliation(s)
- Hsi-Lung Hsieh
- Department of Nursing, Division of Basic Medical Sciences, Chang-Gung University of Science and Technology, Taoyuan 333, Taiwan
- Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 333, Taiwan
- Department of Neurology, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
| | - Ming-Chin Yu
- Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Taoyuan 333, Taiwan
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
- Department of General Surgery, New Taipei Municipal TuCheng Hospital, New Taipei 236, Taiwan
| | - Li-Ching Cheng
- Department of Nursing, Division of Basic Medical Sciences, Chang-Gung University of Science and Technology, Taoyuan 333, Taiwan
| | - Ta-Sen Yeh
- Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Taoyuan 333, Taiwan
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
| | - Ming-Ming Tsai
- Department of Nursing, Division of Basic Medical Sciences, Chang-Gung University of Science and Technology, Taoyuan 333, Taiwan
- Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 333, Taiwan
- Department of General Surgery, Chang Gung Memorial Hospital, Chiayi 613, Taiwan.
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Zhao X, Li Y, Yang Z, Zhang H, Wang H, Lin J, Liu J, Zhao Q. Adenocarcinoma with Mixed Subtypes in the Early and Advanced Gastric Cancer. Can J Gastroenterol Hepatol 2021; 2021:8497305. [PMID: 34746042 PMCID: PMC8570884 DOI: 10.1155/2021/8497305] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Accepted: 10/15/2021] [Indexed: 12/09/2022] Open
Abstract
Objective Adenocarcinoma with mixed subtypes (AM) is a histological classification based on the WHO classification. We aimed to compare the prognosis among AM, classic adenocarcinoma (CA), mucinous adenocarcinoma (MAC), and signet-ring cell carcinoma (SRCC) in early and advanced gastric cancer (EGC and AGC), respectively. Methods The Surveillance, Epidemiology, and End Results (SEER) database was queried from 2001 to 2016. Univariate and multivariate Cox analyses were performed to compare prognosis between AM and histologic subtypes of CA, SRCC, and MAC in ECG and ACG. A nomogram was established to predict the cancer-specific survival (CSS) of gastric cancer (GC) patients with AM. C-index, calibration curves, and receiver operating characteristic (ROC) and decision curve analysis (DCA) curves were applied to examine the accuracy and clinical benefits. Results In the prognosis among these four histological subtypes in EGC patients, there are no differences. For AGC patients, AM had a significantly poorer prognosis compared with CA and MAC (P=0.003, 0.029) but similar prognosis to SRCC. A nomogram based on race, T stage, N stage, M stage, and surgical modalities was proposed to predict 1- and 3-year CSS for GC patients with AM (C-index: training cohort: 0.804, validation cohort: 0.748. 1- and 3-year CSS AUC: training cohort: 0.871 and 0.914, validation cohort: 0.810 and 0.798). 1- and 3-year CSS DCA curves showed good net benefits. Conclusions EGC patients with AM had similar survival to those with CA, MAC, and SRCC. AM was an independent predictor of poor prognosis in AGC. A nomogram for predicting the prognosis of GC patients with AM was proposed to quantitatively assess the long-term survival.
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Affiliation(s)
- Xixian Zhao
- Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
- Hubei Clinical Center & Key Lab of Intestinal & Colorectal Diseases, Wuhan 430071, China
| | - Yizhang Li
- Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
- Hubei Clinical Center & Key Lab of Intestinal & Colorectal Diseases, Wuhan 430071, China
| | - Zhenwei Yang
- Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
- Hubei Clinical Center & Key Lab of Intestinal & Colorectal Diseases, Wuhan 430071, China
| | - Hailin Zhang
- Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
- Hubei Clinical Center & Key Lab of Intestinal & Colorectal Diseases, Wuhan 430071, China
| | - Hongling Wang
- Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
- Hubei Clinical Center & Key Lab of Intestinal & Colorectal Diseases, Wuhan 430071, China
| | - Jun Lin
- Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
- Hubei Clinical Center & Key Lab of Intestinal & Colorectal Diseases, Wuhan 430071, China
| | - Jing Liu
- Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
- Hubei Clinical Center & Key Lab of Intestinal & Colorectal Diseases, Wuhan 430071, China
| | - Qiu Zhao
- Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
- Hubei Clinical Center & Key Lab of Intestinal & Colorectal Diseases, Wuhan 430071, China
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Jeong SH, Kim JW, Kim HM. Prevalence of Regional Lymph Node Metastasis of Mucosal Gastric Signet Ring Cell Carcinoma: Analysis of the Collaborative Stage Data Survey of the Korean Central Cancer Registry. Dig Surg 2021; 38:330-336. [PMID: 34521093 DOI: 10.1159/000518898] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2021] [Accepted: 08/02/2021] [Indexed: 12/10/2022]
Abstract
INTRODUCTION Patients with very early-stage gastric signet ring cell carcinoma (SRC) are eligible for minimally invasive treatment, like endoscopic submucosal dissection. However, population-based data on regional lymph node metastasis (LNM) and distant metastasis of gastric SRC are lacking. This study aimed to identify the prevalence of LNM and distant metastasis in mucosal cancer (T1a) of gastric SRC. METHODS The Collaborative Stage Data Survey was performed by the Korean Center of Cancer Registry between 2010 and 2015 to establish collaborative stage data of the stomach, colon, rectum, rectosigmoid junction, and breast. From the survey data, information on patients with gastric SRC was extracted for analysis. Variables including age, sex, diagnosis date, primary site, tumor size, histology, American Joint Committee on Cancer staging system scores, and Surveillance, Epidemiology, and End Results summary stage were analyzed. RESULTS A total of 1,335 (65.7%) patients had mucosal gastric SRC, and 1,189 (89.1%) patients had surgery and 134 (10%) had endoscopic treatment. Of them, 1,283 (96.1%) patients did not have regional LNM, and 52 (3.9%) patients had regional LNM and 6 (0.4%) had distant metastasis. The hazard ratios of LNM and distant metastasis were 14.98 (95% CI: 4.18-53.2) and 10.09 (95% CI: 2.30-44.17). CONCLUSIONS Reginal LNM and distant metastasis occur very less in mucosal gastric SRC, but they are associated with an increased risk of cancer-related death. Even in early stage, surgery should be considered as a standard treatment of mucosal gastric SRC.
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Affiliation(s)
- Seok-Hoo Jeong
- Division of Gastroenterology, Department of Internal Medicine, Catholic Kwandong University International St. Mary's Hospital, Incheon, Republic of Korea
| | - Jin Woo Kim
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea,
| | - Hee Man Kim
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea
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Efared B, Kadi M, Tahiri L, Lahmidani N, Hassani KIM, Bouhaddouti HE, Benbrahim Z, Adil IS, Chbani L. Gastric Signet Ring Cell Carcinoma: A Comparative Analysis of Clinicopathologic Features. Cancer Control 2021; 27:1073274820976596. [PMID: 33269609 PMCID: PMC8480344 DOI: 10.1177/1073274820976596] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Signet ring cell carcinoma (SRC) is a distinct histological subtype of gastric carcinoma. Our aim is to investigate differential characteristics between gastric SRC and other non SRC carcinomas (nSRC). It was a retrospective study including 183 patients diagnosed with gastric carcinoma over a period of 5 years at our pathology department. We performed statistical comparison of clinicopathological features between patients with SRC and those with nSRC. 127 patients (69.4%) had nSRC, 56 had SRC (30.6%), the mean age was 56.67 ± 14.03 years. Patients with SRC were younger than those with nSRC (mean age of 49.66 versus 59.76, P = 0.030). Patients with SRC tend to have more diffuse tumors in the stomach (P = 0.005), with flat macroscopic appearance (P = 0.001). Patients with SRC present more often with pT3 tumors (P < 0.001), lymph node metastasis (P = 0.024) and perineural invasion (P = 0.003). There were no significant differences between SRC and nSRC in gender, vascular invasion or distant metastasis (P > 0.05). The median survival time was 42.82 ± 1.70 months. Patients with nSRC live longer than those with SRC, but the difference was not significant (P = 0.28). SRC is a histological subtype of gastric carcinoma with distinctive clinicopathologic features. The clinical management of patients should take into account these particular features.
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Affiliation(s)
- Boubacar Efared
- Department of Pathology, Hassan II University Hospital, Fès, Morocco.,Laboratory of Pathology, Faculty of Medicine, Abdou Moumouni University, Niamey, Niger
| | - Mohamed Kadi
- Department of Pathology, Hassan II University Hospital, Fès, Morocco
| | - Laila Tahiri
- Department of Pathology, Hassan II University Hospital, Fès, Morocco.,Laboratory of Biomedical and Translational Research, Faculty of Medicine and Pharmacology, Sidi Mohamed Ben Abdallah University, Fès, Morocco
| | - Nada Lahmidani
- Department of Hepatogastroenterology, Hassan II University Hospital, Sidi Mohamed Ben Abdallah University, Fès, Morocco
| | - Karim Ibn Majdoub Hassani
- Department of General and Visceral Surgery, Hassan II University Hospital, Sidi Mohamed Ben Abdallah University, Fès, Morocco
| | - Hicham El Bouhaddouti
- Department of General and Visceral Surgery, Hassan II University Hospital, Sidi Mohamed Ben Abdallah University, Fès, Morocco
| | - Zineb Benbrahim
- Department of Oncology, Hassan II University Hospital, Sidi Mohamed Ben Abdallah University, Fès, Morocco
| | - Ibrahimi Sidi Adil
- Department of Hepatogastroenterology, Hassan II University Hospital, Sidi Mohamed Ben Abdallah University, Fès, Morocco
| | - Laila Chbani
- Department of Pathology, Hassan II University Hospital, Fès, Morocco.,Laboratory of Biomedical and Translational Research, Faculty of Medicine and Pharmacology, Sidi Mohamed Ben Abdallah University, Fès, Morocco
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Guo Q, Wang Y, An J, Wang S, Dong X, Zhao H. A Prognostic Model for Patients With Gastric Signet Ring Cell Carcinoma. Technol Cancer Res Treat 2021; 20:15330338211027912. [PMID: 34190015 PMCID: PMC8258759 DOI: 10.1177/15330338211027912] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Background: The aim of our study was to develop a nomogram model to predict overall survival (OS) and cancer-specific survival (CSS) in patients with gastric signet ring cell carcinoma (GSRC). Methods: GSRC patients from 2004 to 2015 were collected from the Surveillance, Epidemiology, and End Results (SEER) database and randomly assigned to the training and validation sets. Multivariate Cox regression analyses screened for OS and CSS independent risk factors and nomograms were constructed. Results: A total of 7,149 eligible GSRC patients were identified, including 4,766 in the training set and 2,383 in the validation set. Multivariate Cox regression analysis showed that gender, marital status, race, AJCC stage, TNM stage, surgery and chemotherapy were independent risk factors for both OS and CSS. Based on the results of the multivariate Cox regression analysis, prognostic nomograms were constructed for OS and CSS. In the training set, the C-index was 0.754 (95% CI = 0.746-0.762) for the OS nomogram and 0.762 (95% CI: 0.753-0.771) for the CSS nomogram. In the internal validation, the C-index for the OS nomogram was 0.758 (95% CI: 0.746-0.770), while the C-index for the CSS nomogram was 0.762 (95% CI: 0.749-0.775). Compared with TNM stage and SEER stage, the nomogram had better predictive ability. In addition, the calibration curves also showed good consistency between the predicted and actual 3-year and 5-year OS and CSS. Conclusion: The nomogram can effectively predict OS and CSS in patients with GSRC, which may help clinicians to personalize prognostic assessments and clinical decisions.
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Affiliation(s)
- Qinping Guo
- Department of General Surgery, Shanxi Bethune Hospital, Taiyuan, Shanxi Province, China
| | - Yinquan Wang
- Department of General Surgery, Shanxi Bethune Hospital, Taiyuan, Shanxi Province, China
| | - Jie An
- Department of General Surgery, Shanxi Bethune Hospital, Taiyuan, Shanxi Province, China
| | - Siben Wang
- Department of Thoracic Surgery, Huainan First People's Hospital, Huainan, Anhui Province, China
| | - Xiushan Dong
- Department of General Surgery, Shanxi Bethune Hospital, Taiyuan, Shanxi Province, China
| | - Haoliang Zhao
- Department of General Surgery, Shanxi Bethune Hospital, Taiyuan, Shanxi Province, China
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Zhang C, Liu R, Zhang WH, Chen XZ, Liu K, Yang K, Chen XL, Zhao LY, Chen ZX, Zhou ZG, Hu JK. Difference Between Signet Ring Cell Gastric Cancers and Non-Signet Ring Cell Gastric Cancers: A Systematic Review and Meta-Analysis. Front Oncol 2021; 11:618477. [PMID: 34026606 PMCID: PMC8139399 DOI: 10.3389/fonc.2021.618477] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2020] [Accepted: 02/22/2021] [Indexed: 02/05/2023] Open
Abstract
Background: There is controversy about the characteristics and prognostic implications of signet ring cell gastric cancers and non-signet ring cell gastric cancers. Objective: This study aims to evaluate clinicopathological characteristics and prognoses of signet ring cell carcinoma (SRCC) and non-signet ring cell carcinoma (NSRCC) of stomach. Methods: Studies compared between SRCC and NSRCC of the stomach after gastrectomy and published before September 1st, 2020, in the PubMed, Cochrane, and Embase databases, were identified systematically. Results: A total of 2,865 studies were screened, and 36 studies were included, with 19,174 patients in the SRCC group and 55,942 patients in the NSRCC group. SRCC patients were younger in age (P < 0.001), less likely to be male patients (P < 0.001), more afflicted with upper third lesions (P < 0.001), and presenting with more Borrmann type IV tumors (P = 0.005) than NSRCC patients. Lymph nodes metastasis was similar between SRCC and NSRCC patients with advanced tumor stage (OR: 0.86, 95% CI: 0.671.10, P = 0.23), but lower in the SRCC than NSRCC patients with early tumor stage (OR: 0.73; 95% CI: 0.560.98, P = 0.02). SRCC patients had comparable survival outcomes with NSRCC patients for early gastric cancers (HR: 1.05, 95% CI: 0.651.68, P < 0.001) but had significantly poor prognosis for patients with advanced tumor stage (HR: 1.50, 95% CI: 1.281.76, P < 0.001). Conclusions: Signet ring cell carcinomas of the stomach are an increasingly common histopathological subtype of gastric cancers. These kinds of patients tend to be younger in age and more often female. Although, signet ring cell gastric cancer is a negative prognostic factor for patients with advanced stage. The difference is that for early stage of signet ring cell gastric cancers, it has low lymph nodes metastasis rate and comparable prognosis with non-signet ring cell cancers.
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Affiliation(s)
- Chi Zhang
- Department of Gastrointestinal Surgery, Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Ran Liu
- Engineering Research Center of Medical Information Technology, Ministry of Education, West China Hospital, Sichuan University, Chengdu, China
| | - Wei-Han Zhang
- Department of Gastrointestinal Surgery, Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Xin-Zu Chen
- Department of Gastrointestinal Surgery, Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Kai Liu
- Department of Gastrointestinal Surgery, Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Kun Yang
- Department of Gastrointestinal Surgery, Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Xiao-Long Chen
- Department of Gastrointestinal Surgery, Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Lin-Yong Zhao
- Department of Gastrointestinal Surgery, Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Zhi-Xin Chen
- Department of Gastrointestinal Surgery, Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Zong-Guang Zhou
- Department of Gastrointestinal Surgery, Laboratory of Digestive Surgery, State Key Laboratory of Biotherapy, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Jian-Kun Hu
- Department of Gastrointestinal Surgery, Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China
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40
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Fung BM, Patel M, Patel N, Brown AF, Ostrzega NL, Tabibian JH. Signet Ring Cell Gastric Carcinoma: Clinical Epidemiology and Outcomes in a Predominantly Latino County Hospital Population. Dig Dis Sci 2021; 66:1240-1248. [PMID: 32448921 PMCID: PMC10949970 DOI: 10.1007/s10620-020-06341-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2019] [Accepted: 05/12/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Gastric signet ring cell carcinoma (GSRC) is a rare but increasingly prevalent tumor histotype whose clinical features and natural history are poorly understood, particularly in the USA and minorities. AIMS To examine the occurrence, clinico-demographic characteristics, oncologic features, treatment, and outcomes of GSRC in a predominantly minority county hospital setting and benchmark them against data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program. METHODS We queried biopsy-proven GSRC cases at a Los Angeles County hospital, from 2004 to 2017. Clinical characteristics, treatment, and survival data were collected and compared to SEER data. RESULTS We identified 63 patients with GSRC. Compared to SEER, our cohort was significantly younger (52.6 vs. 63.5 years, p < 0.01), Hispanic/Latino predominant (81% vs. 20%, p < 0.01), had higher overall stage (86% vs. 69% with stage III/IV, p < 0.01), and more frequent node involvement (89% vs. 49%, p < 0.01). Lower tumor stage, Helicobacter pylori positivity, and surgical intervention were associated with significantly longer median survival (all p < 0.05), which was similar in our study compared to SEER (median 12.6 vs. 9.0 months, p = 0.26). CONCLUSIONS Patients with GSRC within the Los Angeles County population have different clinical characteristics compared to what has been reported in SEER. Our cohort was younger, and despite having more advanced disease, did not have shorter survival. Further study is needed to better identify protective and risk factors in this population and improve understanding of the etiopathogenesis and natural history of this malignancy.
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Affiliation(s)
- Brian M Fung
- UCLA-Olive View Internal Medicine Residency Program, Sylmar, CA, USA
- David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Mital Patel
- UCLA-Olive View Internal Medicine Residency Program, Sylmar, CA, USA
- David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Neha Patel
- UCLA-Olive View Internal Medicine Residency Program, Sylmar, CA, USA
- David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Arleen F Brown
- Department of Medicine, Olive View-UCLA Medical Center, Sylmar, CA, USA
- David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Nora L Ostrzega
- Department of Pathology and Laboratory Medicine, Olive View-UCLA Medical Center, Sylmar, CA, USA
- David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - James H Tabibian
- David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
- Division of Gastroenterology, Department of Medicine, Olive View-UCLA Medical Center, 14445 Olive View Dr., 2B-182, Sylmar, CA, 91342, USA.
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Liu YY, Liu YW, Chen YY, Wang SH, Chuah SK, Huang GK, Chen YH. The efficacy and toxicity of adjuvant S-1 schedule with 2-week administration followed by 1-week rest in gastric cancer patients. J Gastrointest Oncol 2021; 12:297-306. [PMID: 34012627 DOI: 10.21037/jgo-20-477] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Background This study aimed to investigate the clinical outcome of adjuvant S-1 with 2-week administration followed by a 1-week rest for locally advanced gastric cancer (GC) patients. Methods The current study was a single retrospective cohort study that focused on the efficacy and toxicity of adjuvant S-1 with a 3-week schedule. A total of 60 patients who underwent total or subtotal gastrectomy plus D2 lymph node dissection and adjuvant S-1 treatment were identified. S-1 treatment began within 4 weeks after the operation; it was administered orally for 2 weeks, followed by a 1-week rest. The dose of S-1 was adjusted depending on adverse events (AEs), with at least 80 mg administered daily. The completion of 1-year S-1 was defined as S-1 continuation for 1 year with over 70% of the planned dose. Patients were followed up with for 5 years postoperatively and underwent hematologic tests and assessments of clinical symptoms every 3-6 weeks for 1 year after surgery. Computed tomography of the abdomen and panendoscopy were performed every 6 months during the first 2 years and at 1-year intervals thereafter until year 5 after surgery. Results The completion rate of 1-year adjuvant S-1 was 71.7%, and the 3-year disease-free survival and overall survival rates were 70.2% and 79.5%, respectively. Seventeen patients did not complete S-1 for 1 year, including 11 patients with tumor recurrence and 6 patients who developed intolerance. Most AEs of S-1 were grade 1-2, and the most frequent AEs (>20%) included anemia, fatigue, pigmentation, nausea, and diarrhea. The most common grade 3-4 AE was fatigue, which was observed in 6.7% of patients. Most patients tolerated the side effects. Conclusions The results of our study confirm that the efficacy and safety of schedule modification of adjuvant S-1 treatment in patients with GC who underwent gastrectomy with D2 lymph node dissection are equal to those in a previous phase 3 study.
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Affiliation(s)
- Yu-Yin Liu
- Division of General Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung
| | - Yueh-Wei Liu
- Division of General Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung
| | - Yen-Yang Chen
- Department of Hematology-Oncology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung
| | - Shih-Ho Wang
- Division of General Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung
| | - Seng-Kee Chuah
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung
| | - Gong-Kai Huang
- Department of Anatomic Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung
| | - Yen-Hao Chen
- Department of Hematology-Oncology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung.,School of Medicine, Chung Shan Medical University, Taichung.,Department of Nursing, Meiho University, Pingtung
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Tang D, Ni M, Zhu H, Cao J, Zhou L, Shen S, Peng C, Lv Y, Xu G, Wang L, Zou X. Differential prognostic implications of gastric adenocarcinoma based on Lauren's classification: a Surveillance, Epidemiology, and End Results (SEER)-based cohort study. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:646. [PMID: 33987344 PMCID: PMC8106066 DOI: 10.21037/atm-20-7953] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Background Our study aims to analyze the association between Lauren's classification and gastric adenocarcinoma prognosis using comprehensive statistical analyses. Methods According to the selection criteria, patients were included from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox regression, propensity score matching, and a multivariate competing risk model were used to investigate the association between Lauren's classification and prognosis. Subgroup analysis was used to investigate the role of confounding factors on the association between Lauren types and prognosis. Results After exclusion, a total of 20,218 patients from the SEER database were included, with 14,374 intestinal types and 5,844 diffuse types. The univariate Cox regression analysis revealed that the diffuse type had a poorer cancer-specific survival (CSS) rate [hazard ratio (HR), 1.44; 95% confidence interval (CI), 1.38-1.50]. After adjusting for confounding variables, the diffuse type also showed a higher risk of cancer-specific death (HR, 1.20; 95% CI, 1.15-1.20). Sensitivity analysis showed that after propensity score matching, the diffuse type had a poorer CSS rate (HR, 1.23; 95% CI, 1.10-1.36), and the competing risk model further validated these results [subdistribution HR (SHR), 1.32; 95% CI, 1.23-1.41]. Moreover, subgroup analysis demonstrated stable results in the subgroups, except for patients with T1 stage (HR, 1.06; 95% CI, 0.87-1.28) and a tumor size <2 cm (HR, 1.00; 95% CI, 0.83-1.21). Conclusions Diffuse-type gastric adenocarcinoma had an overall poorer prognosis compared to the intestinal type. However, in patients with T1 stage and tumor size <2 cm, the diffuse type had a comparable survival rate with the intestinal type.
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Affiliation(s)
- Dehua Tang
- Department of Gastroenterology, Nanjing Drum Tower Hospital, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China
| | - Muhan Ni
- Department of Gastroenterology, Nanjing Drum Tower Hospital, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China
| | - Hao Zhu
- Department of Gastroenterology, Nanjing Drum Tower Hospital, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China
| | - Jun Cao
- Department of Gastroenterology, Nanjing Drum Tower Hospital, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China
| | - Lin Zhou
- Department of Gastroenterology, Nanjing Drum Tower Hospital, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China
| | - Shanshan Shen
- Department of Gastroenterology, Nanjing Drum Tower Hospital, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China
| | - Chunyan Peng
- Department of Gastroenterology, Nanjing Drum Tower Hospital, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China
| | - Ying Lv
- Department of Gastroenterology, Nanjing Drum Tower Hospital, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China
| | - Guifang Xu
- Department of Gastroenterology, Nanjing Drum Tower Hospital, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China
| | - Lei Wang
- Department of Gastroenterology, Nanjing Drum Tower Hospital, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China
| | - Xiaoping Zou
- Department of Gastroenterology, Nanjing Drum Tower Hospital, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China
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Cowling J, Gorman B, Riaz A, Bundred JR, Kamarajah SK, Evans RPT, Singh P, Griffiths EA. Peri-operative Outcomes and Survival Following Palliative Gastrectomy for Gastric Cancer: a Systematic Review and Meta-analysis. J Gastrointest Cancer 2021; 52:41-56. [PMID: 32959118 PMCID: PMC7900337 DOI: 10.1007/s12029-020-00519-4] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/09/2020] [Indexed: 02/03/2023]
Abstract
BACKGROUND Many patients with gastric cancer present with late stage disease. Palliative gastrectomy remains a contentious intervention aiming to debulk tumour and prevent or treat complications such as gastric outlet obstruction, perforation and bleeding. METHODS We conducted a systematic review of the literature for all papers describing palliative resections for gastric cancer and reporting peri-operative or survival outcomes. Data from peri-operative and survival outcomes were meta-analysed using random effects modelling. Survival data from patients undergoing palliative resections, non-resective surgery and palliative chemotherapy were also combined. This study was registered with the PROSPERO database (CRD42019159136). RESULTS One hundred and twenty-eight papers which included 58,675 patients contributed data. At 1 year, there was a significantly improved survival in patients who underwent palliative gastrectomy when compared to non-resectional surgery and no treatment. At 2 years following treatment, palliative gastrectomy was associated with significantly improved survival compared to chemotherapy only; however, there was no significant improvement in survival compared to patients who underwent non-resectional surgery after 1 year. Palliative resections were associated with higher rates of overall complications versus non-resectional surgery (OR 2.14; 95% CI, 1.34, 3.46; p < 0.001). However, palliative resections were associated with similar peri-operative mortality rates to non-resectional surgery. CONCLUSION Palliative gastrectomy is associated with a small improvement in survival at 1 year when compared to non-resectional surgery and chemotherapy. However, at 2 and 3 years following treatment, survival benefits are less clear. Any survival benefits come at the expense of increased major and overall complications.
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Affiliation(s)
- Joseph Cowling
- College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
| | - Bethany Gorman
- College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
| | - Afrah Riaz
- College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
| | - James R Bundred
- College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
- College of Medical and Dental Sciences, University of Leeds, Leeds, UK
| | - Sivesh K Kamarajah
- College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
- Department of Upper GI surgery, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS FT, Mindelsohn Way, Birmingham, B15 2TH, UK
| | - Richard P T Evans
- College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
| | - Pritam Singh
- Nottingham Oesophago-Gastric Unit, City Hospital, Hucknall Rd, Nottingham, NG5 1PB, UK
| | - Ewen A Griffiths
- College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
- Department of Upper GI surgery, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS FT, Mindelsohn Way, Birmingham, B15 2TH, UK.
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Jiang L, Ma Z, Ye X, Kang W, Yu J. Clinicopathological factors affecting the effect of neoadjuvant chemotherapy in patients with gastric cancer. World J Surg Oncol 2021; 19:44. [PMID: 33563277 PMCID: PMC7874458 DOI: 10.1186/s12957-021-02157-x] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Accepted: 01/31/2021] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Neoadjuvant chemotherapy is an important part of the comprehensive treatment of advanced gastric cancer (GC). The effect of neoadjuvant chemotherapy plays a key role in the prognosis of GC patients. Pathological response can represent the effect of neoadjuvant chemotherapy. However, evidence focused on pathological response and associated clinicopathological factors in GC patients is quite little. In this retrospective study, the clinicopathological factors affecting the effect of neoadjuvant chemotherapy in GC patients were investigated, and suggestions were proposed to improve the effect of neoadjuvant chemotherapy on GC. METHODS Retrospective analysis was performed on GC patients who received radical surgery after neoadjuvant chemotherapy from February 2016 to December 2019 at Peking Union Medical College Hospital. Relevant clinicopathological data was collected to analyze the factors influencing the effect of neoadjuvant chemotherapy. Chi-square test was used for univariate analysis. Logistic regression was used for multivariate analysis. Receiver operating characteristic curve (ROC) was used to determine the cutoff value of variables which significantly influenced the effect of neoadjuvant chemotherapy. RESULTS A total of 203 GC patients were included in the study. Analyses showed that patients < 60 years old (OR = 1.840 [1.016-3.332], P = 0.044), histological type of poor differentiation or signet-ring cell carcinoma (OR = 2.606 [1.321-5.140], P = 0.006), and weight loss during neoadjuvant chemotherapy (OR = 2.110 [1.161-3.834], P = 0.014) were independent risk factors for neoadjuvant chemotherapy effect. In ROC analysis of weight change and neoadjuvant chemotherapy effect, area under the curve (AUC) was 0.593 (P = 0.024) and cutoff value of weight change was - 2.95%. Chi-square test showed that patients without weight loss during neoadjuvant chemotherapy had a higher rate of oral nutritional supplement (ONS) than patients with weight loss (P = 0.039). CONCLUSIONS Patients <60 years old, histological type of poor differentiation or signet-ring cell carcinoma, and weight loss during neoadjuvant chemotherapy were independent risk factors for neoadjuvant chemotherapy effect in GC patients. Patients with weight loss > 2.95% during neoadjuvant may have a worse chemotherapy effect. Timely nutritional support such as ONS to maintain patients' body weight is crucial for improving the effect of neoadjuvant chemotherapy.
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Affiliation(s)
- Lin Jiang
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujin, Dongcheng District, Beijing, 100730, China
- Graduate School, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100005, China
| | - Zhiqiang Ma
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujin, Dongcheng District, Beijing, 100730, China
| | - Xin Ye
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujin, Dongcheng District, Beijing, 100730, China
| | - Weiming Kang
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujin, Dongcheng District, Beijing, 100730, China
| | - Jianchun Yu
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujin, Dongcheng District, Beijing, 100730, China.
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Wang X, Xia X, Xu E, Yang Z, Shen X, Du S, Chen X, Lu X, Jin W, Guan W. Estrogen Receptor Beta Prevents Signet Ring Cell Gastric Carcinoma Progression in Young Patients by Inhibiting Pseudopodia Formation via the mTOR-Arpc1b/EVL Signaling Pathway. Front Cell Dev Biol 2021; 8:592919. [PMID: 33553141 PMCID: PMC7859346 DOI: 10.3389/fcell.2020.592919] [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: 08/08/2020] [Accepted: 10/30/2020] [Indexed: 12/14/2022] Open
Abstract
Signet ring cell gastric carcinoma (SRCGC) is a poorly differentiated malignancy, and can be highly dangerous in the progression stage. There is a higher male to female ratio among patients with signet ring cell carcinoma as compared to patients with non-SRCGC. ERβ has been found to express in stomach adenocarcinoma, but how it affects tumor progression remains unclear. Here, we studied estrogen receptor beta (ERβ) to explore the role of sex-associated factors in SRCGC. We analyzed the clinicopathological statistics of patients with SRCGC, and conducted a series of in vitro experiments. Immunohistochemistry showed that patients with low ERβ expression were at risk of poor prognosis and higher T stage. In vitro assays indicated that ERβ might prevent SRCGC progression by inhibiting cell proliferation and invasiveness and by promoting anoikis. Western blotting and quantitative RT-PCR proved that the mTOR-Arpc1b/EVL signaling pathway might participate in the negative regulatory role of ERβ. In conclusion, our findings show that ERβ might inhibit the malignancy of signet ring cells in patients with SRCGC, indicating that ERβ might be a potential target in adjuvant treatment.
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Affiliation(s)
- Xingzhou Wang
- Department of General Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.,Department of Neurosurgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Xuefeng Xia
- Department of General Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - En Xu
- Department of General Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Zhi Yang
- Department of General Surgery, Drum Tower Clinical Medical College of Nanjing Medical University, Nanjing, China
| | - Xiaofei Shen
- Department of General Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Shangce Du
- Department of General Surgery, Drum Tower Clinical Medical College of Nanjing Medical University, Nanjing, China
| | - Xiaotong Chen
- Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, China
| | - Xiaofeng Lu
- Department of General Surgery, Drum Tower Clinical Medical College of Nanjing Medical University, Nanjing, China
| | - Wei Jin
- Department of Neurosurgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Wenxian Guan
- Department of General Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.,Department of Neurosurgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
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Zhao B, Lu H, Luo R, Bao S, Mei D, Xu H, Huang B. Different clinicopathologic features and prognostic significance of signet ring cell histology in early and locally advanced gastric cancer patients. Clin Res Hepatol Gastroenterol 2021; 45:101454. [PMID: 32505731 DOI: 10.1016/j.clinre.2020.05.006] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2020] [Revised: 04/30/2020] [Accepted: 05/01/2020] [Indexed: 02/04/2023]
Abstract
BACKGROUND Although many studies have evaluated the prognostic significance of signet ring cell (SRC) histology for gastric cancer (GC) patients, the results were conflicting. The objective of this study was to compare clinicopathologic characteristics between SRC type and other types, and evaluate its impact on survival outcome. METHODS We retrospectively reviewed clinicopathologic and survival data of 1891 patients who underwent curative resection for GC. All patients were divided into differentiated, undifferentiated and SRC type according to the histological classification. The prognostic differences between different types were compared and clinicopathologic factors were analyzed. RESULTS SRC histology type had a poorer disease-free survival (DFS) than differentiated type (5-year DFS, 37.7% vs 52.2%, P<0.001), but there was no prognostic difference between SRC type and undifferentiated type (37.7% vs 41.9%, P>0.05). For early GC patients, SRC type was more frequent in younger, female patients and T1a stage tumors; the 5-year DFS of SRC type was similar to that of any other histology type (P>0.05). SRC type showed more aggressive biological features, including extensive stomach involvement, large tumor size, advanced pTstage and pN stage, than other types for locally advanced GC patients; poorer DFS was observed in SRC type compared with differentiated type. Multivariate analysis indicated that SRC type (HR:1.71, 95%CI:1.10-1.68, P<0.01) and undifferentiated type (HR:1.21, 95%CI:1.04-1.40, P<0.05) were independently associated with poor DFS in locally advanced GC patients. CONCLUSION There was a significant difference between early and locally advanced GC patients with regard to clinicopathologic features and prognostic significance of SRC histology. SRC type was an independent prognostic factor for locally advanced GC patients, but not for early GC patients.
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Affiliation(s)
- Bochao Zhao
- Department of Surgical Oncology, First Affiliated Hospital of China Medical University, No. 155 Nanjing North Street, Heping District, 110001 Shenyang, People's Republic of China
| | - Huiwen Lu
- Department of Surgical Oncology, First Affiliated Hospital of China Medical University, No. 155 Nanjing North Street, Heping District, 110001 Shenyang, People's Republic of China
| | - Rui Luo
- Department of Surgical Oncology, First Affiliated Hospital of China Medical University, No. 155 Nanjing North Street, Heping District, 110001 Shenyang, People's Republic of China
| | - Shiyang Bao
- Department of Surgical Oncology, First Affiliated Hospital of China Medical University, No. 155 Nanjing North Street, Heping District, 110001 Shenyang, People's Republic of China
| | - Di Mei
- Department of Surgical Oncology, First Affiliated Hospital of China Medical University, No. 155 Nanjing North Street, Heping District, 110001 Shenyang, People's Republic of China
| | - Huimian Xu
- Department of Surgical Oncology, First Affiliated Hospital of China Medical University, No. 155 Nanjing North Street, Heping District, 110001 Shenyang, People's Republic of China
| | - Baojun Huang
- Department of Surgical Oncology, First Affiliated Hospital of China Medical University, No. 155 Nanjing North Street, Heping District, 110001 Shenyang, People's Republic of China.
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Qiu J, Xin Y. Incidence and prognosis of undifferentiated cancers of the digestive system: a population-based cohort study. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:15. [PMID: 33553308 PMCID: PMC7859808 DOI: 10.21037/atm-20-1615] [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] [Indexed: 11/06/2022]
Abstract
Background Cases of undifferentiated cancers of the digestive system (UCDS) are occasionally encountered in clinical practice; however, no large-scale studies have described their characteristics. This study aimed to investigate the incidence, prognosis, and treatment strategies of UCDS. Methods We used the data from the Surveillance, Epidemiology, and End Results database to evaluate clinical characteristics in UCDS patients. A cohort of 1,372 patients was included to estimate UCDS incidence; another cohort of 1,816 patients was followed up until December 31, 2017 to evaluate treatment and prognosis. The incidence, trends, treatments, overall survival, and cause-specific survival were assessed. Results The estimated incidence of UCDS was 0.136 per 100,000 people-years [95% confidence interval (CI): 0.129-0.143] from 1975 to 2016 with respect to sex, age, year of diagnosis, race, region, site, income, and education. The age-adjusted rates of UCDS dropped from 0.567 per 100,000 people-years in 1978 to 0.031 per 100,000 people-years in 2016. The rates of surgery, beam radiation, and chemotherapy in patients with UCDS were 37.3%, 17.3%, and 30.7%, respectively. Overall, the 5-year cause-specific survival rate was 18%, with a median cause-specific survival of 4 months. Patient prognosis improved significantly over the decades; stage, site, year of diagnosis, surgery, beam radiation, and chemotherapy were independent prognostic factors for UCDS mortality. Conclusions The incidence of UCDS has decreased in the United States over the past 40 years. Patients benefited from surgery, beam radiation, and chemotherapy. The survival of patients with UCDS has improved. Further research on developing decision-making recommendations for UCDS treatment is crucial.
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Affiliation(s)
- Jingping Qiu
- Department of Radiation oncology, The First Hospital of China Medical University, Shenyang, China.,Laboratory of Gastrointestinal Onco-Pathology, Cancer Institute and General Surgery Institute, The First Hospital of China Medical University, Shenyang, China
| | - Yan Xin
- Laboratory of Gastrointestinal Onco-Pathology, Cancer Institute and General Surgery Institute, The First Hospital of China Medical University, Shenyang, China
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Ahn H, Chung WC, Kim YJ, Ryu S, Lim E. Clinical Outcomes of Mucinous Gastric Carcinomas Compared with Non-mucinous and Signet Ring Cell Carcinomas. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2020; 76:297-303. [PMID: 33199672 DOI: 10.4166/kjg.2020.098] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/07/2020] [Revised: 08/24/2020] [Accepted: 09/23/2020] [Indexed: 12/28/2022]
Abstract
Background/Aims This study examined the clinical features and prognosis of patients with mucinous gastric carcinoma (MGC), non-mucinous gastric carcinoma (NMGC), and signet ring cell gastric carcinoma (SRC). Methods A retrospective cohort study was performed, enrolling 65 patients with MGC from January 2007 to December 2016. During the same period, 1,814 patients with histologically proven gastric cancers underwent curative or palliative operations. One hundred and ninety-five NMGC patients were selected as the 1:3 age- and sex-matched control groups. In addition, 200 SRC patients were identified. This study evaluated the demographic features of the patients, pathologic features of the tumor, and the predictive factors, such as the recurrence-free survival and overall survival. Results The recurrence rates were significantly high in MGC than in NMGC or SRC (both p<0.01). The proportion of early gastric cancer was lower in the MGC group than in the other groups (p<0.01). In addition, metastatic lymph nodes were found more frequently in the MGC group (p<0.01), and the proportion of initial pT4, M1 stage, was highest in the MGC group. The recurrence-free survival and overall survival in the MGC group were significantly lower than those in the NMGC or SRC. Subgroup analysis showed that patients with the same American Joint Committee on Cancer (AJCC) stage of each cancer group showed a similar prognosis. Conclusions MGC frequently presents an advanced stage with an unfavorable prognosis compared to NMGC or SRC. On the other hand, MGC of the same AJCC stage had a similar prognosis to NMGC and SRC.
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Affiliation(s)
- Honggeun Ahn
- Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea
| | - Woo Chul Chung
- Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea
| | - Yeon-Ji Kim
- Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea
| | - Seongyul Ryu
- Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea
| | - Eunsun Lim
- Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea
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Ren H, Zhu J, Yu H, Bazhin AV, Westphalen CB, Renz BW, Jacob SN, Lampert C, Werner J, Angele MK, Bösch F. Angiogenesis-Related Gene Expression Signatures Predicting Prognosis in Gastric Cancer Patients. Cancers (Basel) 2020; 12:cancers12123685. [PMID: 33302481 PMCID: PMC7763234 DOI: 10.3390/cancers12123685] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Revised: 11/27/2020] [Accepted: 12/04/2020] [Indexed: 12/24/2022] Open
Abstract
Simple Summary To elucidate the role of angiogenesis as a prognostic signature in gastric cancer, we analyzed the expression level of 36 angiogenesis-related genes (ARGs) from Stomach Adenocarcinoma (STAD) from The Cancer Genome Atlas (TCGA). Consensus clustering analysis showed two major angiogenesis-related types: one related to more aggressive clinicopathological characteristics and worse survival, and the other related to lower tumor, lymph node, metastasis (TNM) stage and better outcomes. Our analysis of TCGA with a least absolute shrinkage and selection operator (LASSO) regression model identified 10 genes associated with overall survival in gastric cancer patients. With this gene signature, we computed angiogenesis-related gene signature risk scores for individual cancer patients that predicted overall and disease-free survival, which were further validated in the independent dataset Asian Cancer Research Group (ACRG). Moreover, an overall survival (OS)-related nomogram was established and had better performance in prognosis prediction than TNM stage. Our analysis provides a comprehensive map of ARGs that can be serve as useful biomarkers for gastric cancer. Abstract Increasing evidence indicates that angiogenesis is crucial in the development and progression of gastric cancer (GC). This study aimed to develop a prognostic relevant angiogenesis-related gene (ARG) signature and a nomogram. The expression profile of the 36 ARGs and clinical information of 372 GC patients were extracted from The Cancer Genome Atlas (TCGA). Consensus clustering was applied to divide patients into clusters 1 and 2. Least absolute shrinkage and selection operator (LASSO) Cox regression analyses were used to identify the survival related ARGs and establish prognostic gene signatures, respectively. The Asian Cancer Research Group (ACRG) (n = 300) was used for external validation. Risk score of ARG signatures was calculated, and a prognostic nomogram was developed. Gene set enrichment analysis of the ARG model risk score was performed. Cluster 2 patients had more advanced clinical stage and shorter survival rates. ARG signatures carried prognostic relevance in both cohorts. Moreover, ARG-risk score was proved as an independent prognostic factor. The predictive value of the nomogram incorporating the risk score and clinicopathological features was superior to tumor, lymph node, metastasis (TNM) staging. The high-risk score group was associated with several cancer and metastasis-related pathways. The present study suggests that ARG-based nomogram could serve as effective prognostic biomarkers and allow a more precise risk stratification.
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Affiliation(s)
- Haoyu Ren
- Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich, D-81377 Munich, Germany; (H.R.); (H.Y.); (A.V.B.); (B.W.R.); (S.N.J.); (C.L.); (J.W.); (M.K.A.)
| | - Jiang Zhu
- Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China;
| | - Haochen Yu
- Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich, D-81377 Munich, Germany; (H.R.); (H.Y.); (A.V.B.); (B.W.R.); (S.N.J.); (C.L.); (J.W.); (M.K.A.)
| | - Alexandr V. Bazhin
- Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich, D-81377 Munich, Germany; (H.R.); (H.Y.); (A.V.B.); (B.W.R.); (S.N.J.); (C.L.); (J.W.); (M.K.A.)
| | - Christoph Benedikt Westphalen
- Department of Medicine 3 and Comprehensive Cancer Center, Ludwig-Maximilians-University Munich, D-81377 Munich, Germany;
| | - Bernhard W. Renz
- Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich, D-81377 Munich, Germany; (H.R.); (H.Y.); (A.V.B.); (B.W.R.); (S.N.J.); (C.L.); (J.W.); (M.K.A.)
| | - Sven N. Jacob
- Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich, D-81377 Munich, Germany; (H.R.); (H.Y.); (A.V.B.); (B.W.R.); (S.N.J.); (C.L.); (J.W.); (M.K.A.)
| | - Christopher Lampert
- Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich, D-81377 Munich, Germany; (H.R.); (H.Y.); (A.V.B.); (B.W.R.); (S.N.J.); (C.L.); (J.W.); (M.K.A.)
| | - Jens Werner
- Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich, D-81377 Munich, Germany; (H.R.); (H.Y.); (A.V.B.); (B.W.R.); (S.N.J.); (C.L.); (J.W.); (M.K.A.)
| | - Martin K. Angele
- Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich, D-81377 Munich, Germany; (H.R.); (H.Y.); (A.V.B.); (B.W.R.); (S.N.J.); (C.L.); (J.W.); (M.K.A.)
| | - Florian Bösch
- Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich, D-81377 Munich, Germany; (H.R.); (H.Y.); (A.V.B.); (B.W.R.); (S.N.J.); (C.L.); (J.W.); (M.K.A.)
- Correspondence: ; Tel.:+49-89-4400-72781; Fax: +49-89-4400-75474
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Prognostic analysis of gastric signet ring cell carcinoma and mucinous carcinoma: a propensity score-matched study and competing risk analysis. Aging (Albany NY) 2020; 12:22059-22077. [PMID: 33130635 PMCID: PMC7695374 DOI: 10.18632/aging.104048] [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: 02/25/2020] [Accepted: 08/31/2020] [Indexed: 12/11/2022]
Abstract
Background: Limited evidence and contradictory results have been reported regarding the impact of signet ring cell carcinoma (SRC) and mucinous gastric cancer (MGC) classifications on the prognosis of gastric cancer (GC). Results: Information on 6017 patients and 266 patients was extracted from the SEER database and our hospital records, respectively. We found that patients with MGC had a better survival rate than those with SRC (P=0.012), but in the early stage, MGC was a risk factor for a poor prognosis. After PSM, for both patients from the SEER database and our hospital, the prognosis of patients with SRC was poorer than that of patients with MGC (P<0.05), but patients with MGC in early-stage GC showed poorer survival. Additionally, SRC was demonstrated to be a risk factor in the multivariate competing risk regression model for cancer-specific survival. Conclusion: Patients with SRC may have a worse prognosis than those with MGC, but for early-stage GC, patients with SRC have a better prognosis than those with MGC. Method: Patients from the SEER database and from our hospital diagnosed with SRC or MGC were included in a Cox regression analysis, multivariate competing risk model and propensity score matching (PSM) analysis.
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