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Wang SY, Wang JH, Chen RK, Yuan Z, Cui H, Wei B, Cui JX. Mapping the landscape of gastric signet ring cell carcinoma: Overcoming hurdles and charting new paths for advancement. World J Clin Oncol 2025; 16:98983. [PMID: 39995554 PMCID: PMC11686557 DOI: 10.5306/wjco.v16.i2.98983] [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: 07/10/2024] [Revised: 09/26/2024] [Accepted: 11/13/2024] [Indexed: 12/11/2024] Open
Abstract
BACKGROUND In recent years, the global prevalence of gastric cancer (GC) has witnessed a progressive decrease, accompanied by a step-growth in the incidence of gastric signet ring cell carcinoma (GSRCC). As precision medicine concepts progress, GSRCC, a distinct sub-type of GC, has drawn considerable attention from researchers. However, there still persist some controversies regarding the associated research findings. AIM To summarize the current obstacles and potential future directions for research on GSRCC. METHODS To begin with, all literature related to GSRCC published from January 1, 2004 to December 31, 2023 was subjected to bibliometric analysis in this article. Additionally, this paper analyzed the research data using CiteSpace, GraphPad Prism v8.0.2, and VOSviewer, which was obtained from the Web of Science Core Collection database. The analysis results were visually represented. RESULTS This study provided a comprehensive overview of the statistical characteristics of the 995 English articles related to GSRCC, including cited references, authors, journals, countries, institutions, and keywords. The popular keywords and clusters contain "prognosis", "survival", "expression", "histology", and "chemotherapy". CONCLUSION The prognosis, precise definition and classification, as well as chemoresistance of GSRCC, continue to be crucial areas of ongoing research, whose directions are closely tied to advancements in molecular biology research on GSRCC.
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Affiliation(s)
- Shu-Yuan Wang
- School of Medicine, Nankai University, Tianjin 300071, China
| | - Jing-Hang Wang
- School of Medicine, Nankai University, Tianjin 300071, China
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Run-Kai Chen
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Zhen Yuan
- School of Medicine, Nankai University, Tianjin 300071, China
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Hao Cui
- School of Medicine, Nankai University, Tianjin 300071, China
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Bo Wei
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Jian-Xin Cui
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
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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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Shariff H, Luu T, Kavis H, Obuch J. Gastric Signet Ring Cell Adenocarcinoma With Metastasis to the Testicles and Leptomeninges. ACG Case Rep J 2024; 11:e01419. [PMID: 39081301 PMCID: PMC11286243 DOI: 10.14309/crj.0000000000001419] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2024] [Accepted: 05/31/2024] [Indexed: 08/02/2024] Open
Abstract
Gastric signet ring cell adenocarcinoma (SRCA) is an aggressive malignancy primarily diagnosed in advanced stages. Metastasis to other organ systems is uncommon, however, associated with poor prognosis. We present a young patient with persistent pain in the testicle. Histopathologic examination of the resected testicle revealed metastatic signet ring adenocarcinoma prompting follow-up endoscopy with biopsy confirming gastric SRCA. After 10 months of systemic chemotherapy, the patient developed worsening headaches, and cerebrospinal fluid cytology confirmed leptomeningeal metastasis. This case underscores the rare manifestation of SRCA and the importance of vigilance for atypical presentations to ensure timely diagnosis and management.
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Affiliation(s)
| | - Tristan Luu
- Department of Internal Medicine, Geisinger Wyoming Valley Medical Center, Wilkes Barre, PA
| | - Haluk Kavis
- Department of Clinical and Laboratory Pathology, Geisinger Medical Center, Danville, PA
| | - Joshua Obuch
- Department of Gastroenterology, Geisinger Wyoming Valley Medical Center, Wilkes Barre, PA
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Schiefer S, Crnovrsanin N, Kalkum E, Vey JA, Nienhüser H, Rompen IF, Haag GM, Müller-Stich B, Billmann F, Schmidt T, Probst P, Klotz R, Sisic L. Is neoadjuvant chemotherapy followed by surgery the appropriate treatment for esophagogastric signet ring cell carcinomas? A systematic review and meta-analysis. Front Surg 2024; 11:1382039. [PMID: 38770165 PMCID: PMC11102960 DOI: 10.3389/fsurg.2024.1382039] [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: 02/04/2024] [Accepted: 04/16/2024] [Indexed: 05/22/2024] Open
Abstract
Background The impact of neoadjuvant chemotherapy (nCTX) on survival and tumor response in patients with esophagogastric signet ring cell carcinoma (SRCC) is still controversial. Methods Two independent reviewers performed a systematic literature search in Medline, CENTRAL, and Web of Science including prospective and retrospective two-arm non-randomized and randomized controlled studies (RCTs). Data was extracted on overall survival (OS) and tumor regression in resected esophagogastric SRCC patients with or without nCTX. Survival data was analyzed using published hazard ratios (HR) if available or determined it from other survival data or survival curves. OS and histopathological response rates by type of tumor (SRCC vs. non-SRCC) were also investigated. Results Out of 559 studies, ten (1 RCT, 9 non-RCTs) were included in this meta-analysis (PROSPERO CRD42022298743) investigating 3,653 patients in total. The four studies investigating survival in SRCC patients treated with nCTX + surgery vs. surgery alone showed no survival benefit for neither intervention, but heterogeneity was considerable (HR, 1.01; 95% CI, 0.61-1.67; p = 0.98; I2 = 89%). In patients treated by nCTX + surgery SRCC patients showed worse survival (HR, 1.45; 95% CI, 1.21-1.74; p < 0.01) and lower rate of major histopathological response than non-SRCC patients (OR, 2.47; 95% CI, 1.78-3.44; p < 0.01). Conclusion The current meta-analysis could not demonstrate beneficial effects of nCTX for SRCC patients. Histopathological response to and survival benefits of non-taxane-based nCTX seem to be lower in comparison to non-SRC esophagogastric cancer. However, certainty of evidence is low due to the scarcity of high-quality trials. Further research is necessary to determine optimal treatment for SRCC patients. Systematic Review Registration https://www.crd.york.ac.uk/, PROSPERO (CRD42022298743).
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Affiliation(s)
- Sabine Schiefer
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Nerma Crnovrsanin
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
- Department of Pathology, Netherlands Cancer Institute (NKI), Amsterdam, Netherlands
| | - Eva Kalkum
- Study Center of the German Society of Surgery (SDGC), University Hospital Heidelberg, Heidelberg, Germany
| | - Johannes A. Vey
- Institute of Medical Biometry (IMBI), University of Heidelberg, Heidelberg, Germany
| | - Henrik Nienhüser
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Ingmar F. Rompen
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Georg M. Haag
- Department of Medical Oncology, National Center for Tumor Diseases (NCT), University Hospital Heidelberg, Heidelberg, Germany
| | - Beat Müller-Stich
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
- Department of Visceral Surgery, University Center for Gastrointestinal and Liver Diseases, St. Clara Hospital and University Hospital, Basel, Switzerland
| | - Franck Billmann
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Thomas Schmidt
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
- Department of General, Visceral, Cancer and Transplant Surgery, University Hospital Cologne, Cologne, Germany
| | - Pascal Probst
- Department of Surgery, Cantonal Hospital Thurgau, Münsterlingen, Switzerland
| | - Rosa Klotz
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
- Study Center of the German Society of Surgery (SDGC), University Hospital Heidelberg, Heidelberg, Germany
| | - Leila Sisic
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
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Wu J, Wang H, Yin X, Wang Y, Lu Z, Zhang J, Zhang Y, Xue Y. Normalization weighted combination scores re-evaluate TNM staging of gastric cancer: a retrospective cohort study based on a multicenter database. Int J Surg 2024; 110:11-22. [PMID: 38000074 PMCID: PMC10793834 DOI: 10.1097/js9.0000000000000726] [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: 06/30/2023] [Accepted: 08/21/2023] [Indexed: 11/26/2023]
Abstract
BACKGROUND The pathological depth of tumor invasion (pT) and lymph node metastasis (pN) are critical independent prognostic factors for patients with gastric cancer (GC), representing effective methods for evaluating prognosis. In this study, the authors employed a normalization weight combination score to calculate the weight ratio of the pT stage and pN stage. Subsequently, the authors established a novel weighted TN (wTN) staging model based on these T and N weights, evaluating its prognostic capacity. METHODS This study utilized a training cohort from A Medical University Cancer Hospital and a validation cohort from the SEER database. Least absolute shrinkage and selection operator (LASSO) and Cox regression were employed to screen clinical characteristics. Multivariate linear regression and cluster analysis calculated the weight ratio of T stage and N stage in the training and validation cohorts, respectively, followed by re-staging. Prognostic value was evaluated using C-index, likelihood ratio, Wald, and Score tests for wTN stage and tumor-node-metastasis (TNM) stage. A nomogram model was developed, and accuracy was assessed using receiver operating characteristic curve (ROC), decision curve analysis (DCA), and restricted cubic spline (RCS) analyses. RESULTS LASSO was used for initial screening, selecting eight potential features for Cox analysis. Age, tumor size, metastasis lymph nodes (MLNs), and tumor location were confirmed as independent prognostic factors. wTN was calculated in the training and validation cohorts, and nomograms were established with the independent factors. N stage had a higher weight proportion than T stage in both cohorts (0.625/0.375 in training cohort, 0.556/0.444 in validation cohort). wTN outperformed the 8th TNM stage in C-index, likelihood ratio, Wald, and Score tests in the training cohort, with successful validation in the validation cohort. Stratified analysis of distinct pathological types further demonstrates that wTN staging exhibits superior prognostic performance. CONCLUSION The wTN staging model based on T stage and N stage weights has a good prognostic value for GC patients. The same conclusion was obtained in different pathological stratification.
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Affiliation(s)
| | | | | | | | | | | | | | - Yingwei Xue
- Department of Gastroenterological Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, People’s Republic of China
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Wang W, Xia Y, He C. Development and validation of a predictive model associated with lymph node metastasis of gastric signet ring carcinoma patients. Medicine (Baltimore) 2023; 102:e36002. [PMID: 37960779 PMCID: PMC10637419 DOI: 10.1097/md.0000000000036002] [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: 09/02/2023] [Accepted: 10/17/2023] [Indexed: 11/15/2023] Open
Abstract
The risk factors for lymph node metastasis (LNM) in patients with gastric signet ring cell carcinoma (GSRC) have not been well-defined. This study was designed to prognosticate LNM in patients with GSRC by constructing and verifying a nomogram. A total of 2789 patients with GSRC from the Surveillance, Epidemiology, and End Results (SEER) database and Yijishan Hospital of Wannan Medical College (YJS) were retrospectively reviewed. A predictive model was established using logistic regression based on the SEER cohort. The performance of the model was evaluated using the concordance index (C-index) and decision curve analysis (DCA). In addition, its robustness was validated using the YJS cohort. Four independent predictors of LNM were identified in the SEER cohort. Next, a nomogram was constructed by incorporating these predictors. The C-index were 0.800 (95% confidence interval [CI] = 0.781-0.819) and 0.837 (95% CI = 0.784-0.890) in the training and external validation cohorts, respectively. The outcomes of DCA supported good clinical benefits. The proposed model for evaluating the LNM in patients with GSRC can help to avoid the misdiagnosis risk of N-stage, assist to screen the population suitable for neoadjuvant therapy and help clinicians to optimize clinical decisions.
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Affiliation(s)
- Wei Wang
- Department of Gastroenterology, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui, People’s Republic of China
| | - Yang Xia
- Department of Gastroenterology, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui, People’s Republic of China
- Department of Gastroenterology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu Province, People’s Republic of China
| | - Chiyi He
- Department of Gastroenterology, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui, People’s Republic of China
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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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Tang YH, Ren LL, Mao T. Update on diagnosis and treatment of early signet-ring cell gastric carcinoma: A literature review. World J Gastrointest Endosc 2023; 15:240-247. [PMID: 37138936 PMCID: PMC10150283 DOI: 10.4253/wjge.v15.i4.240] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2022] [Revised: 02/02/2023] [Accepted: 03/30/2023] [Indexed: 04/14/2023] Open
Abstract
Gastric signet-ring cell gastric carcinoma (GSRC) is an unfavorable subtype of gastric cancer (GC) that presents with greater invasiveness and poorer prognosis in advanced stage than other types of GC. However, GSRC in early stage is often considered an indicator of less lymph node metastasis and more satisfying clinical outcome compared to poorly differentiated GC. Therefore, the detection and diagnosis of GSRC at early stage undoubtedly play a crucial role in the management of GSRC patients. In recent years, technological advancement in endoscopy including narrow-band imaging and magnifying endoscopy has significantly improved the accuracy and sensitivity of the diagnosis under endoscopy for GSRC patients. Researches have confirmed that early stage GSRC that meets the expanded criteria of endoscopic resection showed comparable outcomes to surgery after receiving endoscopic submucosal dissection (ESD), indicating that ESD could be considered standard treatment for GSRC after thorough selection and evaluation. This article summarizes the current knowledge and updates pertaining to the endoscopic diagnosis and treatment of early stage signet-ring cell gastric carcinoma.
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Affiliation(s)
- Yun-He Tang
- Department of Gastroenterology, Affiliated Hospital of Qingdao University, Qingdao 266000, Shandong Province, China
| | - Lin-Lin Ren
- Department of Gastroenterology, Affiliated Hospital of Qingdao University, Qingdao 266000, Shandong Province, China
| | - Tao Mao
- Department of Gastroenterology, Affiliated Hospital of Qingdao University, Qingdao 266000, Shandong Province, China
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Xu J, Zhu J, Lin L, Li Z, Gu F, Wang F, Zhai H. Endoscopic and clinicopathologic features of early gastric signet ring cell carcinoma ≤20 mm: a retrospective observational study. Scand J Gastroenterol 2023; 58:38-44. [PMID: 35850581 DOI: 10.1080/00365521.2022.2100227] [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: 02/04/2023]
Abstract
OBJECTIVES Limited literature exists on the characteristics of early gastric signet ring cell carcinoma (GSRCC) within 20 mm. This study aimed to explore this type of cancer from several aspects, to provide guidance for early detection and intervention of GSRCC. METHODS We retrospectively collected data from 24 patients diagnosed with early GSRCC ≤20 mm in Beijing Friendship Hospital from 2016 to 2021. According to tumor size, those lesions were divided into three groups: diminutive group (1-5 mm, n = 4), small group (6-10 mm, n = 12) and intermediate group (11-20 mm, n = 8). The clinicopathologic and endoscopic characteristics of GSRCC were compared among the three groups. RESULTS Treatment strategies for lesions differed according to the size (p<.05). There were no significant differences among the three groups with regard to age, sex, Helicobacter pylori infection, tumor location and macroscopic type. Lesions were often flat type and more likely to present with discoloration, uneven color, ulceration and submucosal invasion with the increase of diameter. Almost all cases showed abnormal intervening part (IP) under magnifying endoscopy. CONCLUSIONS The location of early signet ring cell carcinoma is not specific, and the diminutive lesions are often flat. Abnormal IP may be the early endoscopic feature of early GSRCC.
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Affiliation(s)
- Jianing Xu
- Department of Gastroenterology and Hepatology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, China
| | - Jingyi Zhu
- Department of Gastroenterology and Hepatology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, China
| | - Lanhui Lin
- Department of Gastroenterology and Hepatology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, China
| | - Zhiyu Li
- Department of Gastroenterology and Hepatology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, China
| | - Feng Gu
- Department of Gastroenterology and Hepatology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, China
| | - Fangning Wang
- Department of Gastroenterology and Hepatology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, China
| | - Huihong Zhai
- Department of Gastroenterology and Hepatology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, China
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Park YS, Kook MC, Kim BH, Lee HS, Kang DW, Gu MJ, Shin OR, Choi Y, Lee W, Kim H, Song IH, Kim KM, Kim HS, Kang G, Park DY, Jin SY, Kim JM, Choi YJ, Chang HK, Ahn S, Chang MS, Han SH, Kwak Y, Seo AN, Lee SH, Cho MY. A Standardized Pathology Report for Gastric Cancer: 2nd Edition. J Gastric Cancer 2023; 23:107-145. [PMID: 36750994 PMCID: PMC9911618 DOI: 10.5230/jgc.2023.23.e7] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2022] [Revised: 12/22/2022] [Accepted: 12/23/2022] [Indexed: 01/27/2023] Open
Abstract
The first edition of 'A Standardized Pathology Report for Gastric Cancer' was initiated by the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists and published 17 years ago. Since then, significant advances have been made in the pathologic diagnosis, molecular genetics, and management of gastric cancer (GC). To reflect those changes, a committee for publishing a second edition of the report was formed within the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. This second edition consists of two parts: standard data elements and conditional data elements. The standard data elements contain the basic pathologic findings and items necessary to predict the prognosis of GC patients, and they are adequate for routine surgical pathology service. Other diagnostic and prognostic factors relevant to adjuvant therapy, including molecular biomarkers, are classified as conditional data elements to allow each pathologist to selectively choose items appropriate to the environment in their institution. We trust that the standardized pathology report will be helpful for GC diagnosis and facilitate large-scale multidisciplinary collaborative studies.
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Affiliation(s)
- Young Soo Park
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | | | - Baek-Hui Kim
- Department of Pathology, Korea University Guro Hospital, Seoul, Korea
| | - Hye Seung Lee
- Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Dong-Wook Kang
- Department of Pathology, Chungnam National University Sejong Hospital, Chungnam National University School of Medicine, Sejong, Korea
| | - Mi-Jin Gu
- Department of Pathology, Yeungnam University College of Medicine, Daegu, Korea
| | - Ok Ran Shin
- Department of Hospital Pathology, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu, Korea
| | - Younghee Choi
- Department of Pathology, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, Korea
| | - Wonae Lee
- Department of Pathology, Dankook University College of Medicine, Cheonan, Korea
| | - Hyunki Kim
- Department of Pathology, Yonsei University College of Medicine, Seoul, Korea
| | - In Hye Song
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Kyoung-Mee Kim
- Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Hee Sung Kim
- Department of Pathology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea
| | - Guhyun Kang
- LabGenomics Clinical Laboratories, Seongnam, Korea
| | | | - So-Young Jin
- Department of Pathology, Soonchunhyang University Seoul Hospital, Seoul, Korea
| | - Joon Mee Kim
- Department of Pathology, Inha University School of Medicine, Incheon, Korea
| | - Yoon Jung Choi
- Department of Pathology, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Korea
| | - Hee Kyung Chang
- Department of Pathology, Kosin University Gospel Hospital, Kosin University College of Medicine, Busan, Korea
| | - Soomin Ahn
- Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Mee Soo Chang
- Department of Pathology, Seoul National University Boramae Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Song-Hee Han
- Department of Pathology, Dong-A University College of Medicine, Busan, Korea
| | - Yoonjin Kwak
- Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - An Na Seo
- Department of Pathology, School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital, Daegu, Korea
| | - Sung Hak Lee
- Department of Hospital Pathology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
| | - Mee-Yon Cho
- Department of Pathology, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Korea.
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11
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Park YS, Kook MC, Kim BH, Lee HS, Kang DW, Gu MJ, Shin OR, Choi Y, Lee W, Kim H, Song IH, Kim KM, Kim HS, Kang G, Park DY, Jin SY, Kim JM, Choi YJ, Chang HK, Ahn S, Chang MS, Han SH, Kwak Y, Seo AN, Lee SH, Cho MY, The Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. A standardized pathology report for gastric cancer: 2nd edition. J Pathol Transl Med 2023; 57:1-27. [PMID: 36647283 PMCID: PMC9846007 DOI: 10.4132/jptm.2022.12.23] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2022] [Revised: 12/22/2022] [Accepted: 12/23/2022] [Indexed: 01/18/2023] Open
Abstract
The first edition of 'A Standardized Pathology Report for Gastric Cancer' was initiated by the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists and published 17 years ago. Since then, significant advances have been made in the pathologic diagnosis, molecular genetics, and management of gastric cancer (GC). To reflect those changes, a committee for publishing a second edition of the report was formed within the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. This second edition consists of two parts: standard data elements and conditional data elements. The standard data elements contain the basic pathologic findings and items necessary to predict the prognosis of GC patients, and they are adequate for routine surgical pathology service. Other diagnostic and prognostic factors relevant to adjuvant therapy, including molecular biomarkers, are classified as conditional data elements to allow each pathologist to selectively choose items appropriate to the environment in their institution. We trust that the standardized pathology report will be helpful for GC diagnosis and facilitate large-scale multidisciplinary collaborative studies.
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Affiliation(s)
- Young Soo Park
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | | | - Baek-hui Kim
- Department of Pathology, Korea University Guro Hospital, Seoul, Korea
| | - Hye Seung Lee
- Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Dong-Wook Kang
- Department of Pathology, Chungnam National University Sejong Hospital, Chungnam National University School of Medicine, Sejong, Korea
| | - Mi-Jin Gu
- Department of Pathology, Yeungnam University College of Medicine, Daegu, Korea
| | - Ok Ran Shin
- Department of Hospital Pathology, Uijeongbu St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu, Korea
| | - Younghee Choi
- Department of Pathology, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, Korea
| | - Wonae Lee
- Department of Pathology, Dankook University College of Medicine, Cheonan, Korea
| | - Hyunki Kim
- Department of Pathology, Yonsei University College of Medicine, Seoul, Korea
| | - In Hye Song
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Kyoung-Mee Kim
- Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Hee Sung Kim
- Department of Pathology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea
| | - Guhyun Kang
- LabGenomics Clinical Laboratories, Seongnam, Korea
| | | | - So-Young Jin
- Department of Pathology, Soonchunhyang University Seoul Hospital, Seoul, Korea
| | - Joon Mee Kim
- Department of Pathology, Inha University School of Medicine, Incheon, Korea
| | - Yoon Jung Choi
- Department of Pathology, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Korea
| | - Hee Kyung Chang
- Department of Pathology, Kosin University Gospel Hospital, Kosin University College of Medicine, Busan, Korea
| | - Soomin Ahn
- Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Mee Soo Chang
- Department of Pathology, Seoul National University Boramae Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Song-Hee Han
- Department of Pathology, Dong-A University College of Medicine, Busan, Korea
| | - Yoonjin Kwak
- Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - An Na Seo
- Department of Pathology, School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital, Daegu, Korea
| | - Sung Hak Lee
- Department of Hospital Pathology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Mee-Yon Cho
- Department of Pathology, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - The Gastrointestinal Pathology Study Group of the Korean Society of Pathologists
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
- Center for Gastric Cancer, National Cancer Center, Goyang, Korea
- Department of Pathology, Korea University Guro Hospital, Seoul, Korea
- Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
- Department of Pathology, Chungnam National University Sejong Hospital, Chungnam National University School of Medicine, Sejong, Korea
- Department of Pathology, Yeungnam University College of Medicine, Daegu, Korea
- Department of Hospital Pathology, Uijeongbu St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu, Korea
- Department of Pathology, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, Korea
- Department of Pathology, Dankook University College of Medicine, Cheonan, Korea
- Department of Pathology, Yonsei University College of Medicine, Seoul, Korea
- Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
- Department of Pathology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea
- LabGenomics Clinical Laboratories, Seongnam, Korea
- St. Maria Pathology Laboratory, Busan, Korea
- Department of Pathology, Soonchunhyang University Seoul Hospital, Seoul, Korea
- Department of Pathology, Inha University School of Medicine, Incheon, Korea
- Department of Pathology, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Korea
- Department of Pathology, Kosin University Gospel Hospital, Kosin University College of Medicine, Busan, Korea
- Department of Pathology, Seoul National University Boramae Hospital, Seoul National University College of Medicine, Seoul, Korea
- Department of Pathology, Dong-A University College of Medicine, Busan, Korea
- Department of Pathology, School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital, Daegu, Korea
- Department of Hospital Pathology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Department of Pathology, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Korea
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12
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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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13
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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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14
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Weng CY, Sun SP, Cai C, Xu JL, Lv B. Endoscopic submucosal dissection for early signet ring cell gastric cancer: A systematic review and meta-analysis. World J Clin Cases 2022; 10:6915-6926. [PMID: 36051146 PMCID: PMC9297431 DOI: 10.12998/wjcc.v10.i20.6915] [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: 09/06/2021] [Revised: 11/11/2021] [Accepted: 04/21/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The use of endoscopic submucosal dissection (ESD) for treating early signet ring cell carcinoma (SRC) is controversial due to the risk of lymph node metastasis.
AIM To carry out a meta-analysis to evaluate ESD for therapeutic efficacy and safety in early signet ring cell gastric cancer.
METHODS The PubMed, Web of Science, Cochrane Library, and EMBASE databases were used to search for relevant studies evaluating the therapeutic efficacy and safety of ESD in SRC. The rates of recurrence, complete resection, incomplete resection, curative resection, en bloc resection, and adverse events were extracted and analyzed. The methodological quality of the enrolled studies was assessed using the Newcastle-Ottawa Scale. Publication bias was evaluated by the Egger’s test. Institutional review board approval and written consent were not needed for this report.
RESULTS This meta-analysis enrolled seven studies with 653 participants undergoing ESD treatment for early SRC. The overall recurrence rate was 0.010 [95% confidence interval (CI): 0.000-0.040, Z = 1.422, P = 0.155]. The total lymphovascular invasion rate was 0.038 (95%CI: 0.007-0.088, Z = 3.026, P = 0.002). The total en bloc resection rate was estimated at 0.984 (95%CI: 0.925-1.000, Z = 19.463, P = 0.000). The total complete and incomplete resection rates were estimated at 0.785 (95%CI: 0.596-0.928, Z = 9.789, P = 0.000) and 0.188 (95%CI: 0.016-0.468, Z = 2.531, P = 0.011), respectively. The total procedure-associated gastric hemorrhage and perforation rates were estimated at 0.026 (95%CI: 0.005-0.061, Z = 3.006 P = 0.003) and 0.004 (95%CI: 0.000-0.028, Z = 0.938, P = 0.348), respectively. The curative resection, vertical margin invasion, and lateral margin invasion rates were 72.1% (145/341), 2.3% (8/348), and 34.45% (41/119), respectively.
CONCLUSION ESD constitutes a promising therapeutic approach for early undifferentiated SRC gastric cancer. However, further improvements are required for increasing its treatment efficacy and reducing adverse outcomes.
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Affiliation(s)
- Chun-Yan Weng
- Department of Gastroenterology, The First Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou 310000, Zhejiang Province, China
| | - Shao-Peng Sun
- Department of Gastroenterology, The First Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou 310000, Zhejiang Province, China
| | - Chang Cai
- Department of Gastroenterology, The First Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou 310000, Zhejiang Province, China
| | - Jing-Li Xu
- Department of Gastrointestinal Surgery, The First Clinical Medical University of Zhejiang Chinese Medical University, Hangzhou 310000, Zhejiang Province, China
| | - Bin Lv
- Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China
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15
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Comparison of treatment strategies and survival of early-onset gastric cancer: a population-based study. Sci Rep 2022; 12:6288. [PMID: 35428811 PMCID: PMC9012810 DOI: 10.1038/s41598-022-10156-5] [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: 01/04/2022] [Accepted: 03/29/2022] [Indexed: 11/25/2022] Open
Abstract
Treatments for early-onset gastric cancer (EOGC) patients are rarely included in clinical trials, resulting in an unclear impact on survival. This study aimed to investigate the treatment patterns of EOGC patients and their impact on survival. Based on the Surveillance, Epidemiology, and End Results database, we conducted a retrospective analysis of 1639 EOGC patients (< 50 years) diagnosed between 2010 and 2018. Patients with larger tumours, distant metastasis, and AJCC TNM stage in IV were prone to receive nonsurgical treatment. Patients treated with surgery alone had a better prognosis than those receiving SROC or SCRT or nonsurgical treatment. However, analyses stratified by histological type, tumour size and TNM stage showed that patients did not benefit more from SROC and SCRT than from surgery alone. Similar results were observed in the stratified Cox regression risk analysis. Patients who received nonsurgical treatment had the highest risk of overall death [hazard ratio (HR) = 2.443, 95% confidence interval (CI) 1.865–3.200, P < 0.001]. This study indicated that additional radiotherapy, chemotherapy or chemoradiotherapy did not provide a coordinated survival benefit to EOGC patients.
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16
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Chen T, Wu J, Cui C, He Q, Li X, Liang W, Liu X, Liu T, Zhou X, Zhang X, Lei X, Xiong W, Yu J, Li G. CT-based radiomics nomograms for preoperative prediction of diffuse-type and signet ring cell gastric cancer: a multicenter development and validation cohort. J Transl Med 2022; 20:38. [PMID: 35073917 PMCID: PMC8785479 DOI: 10.1186/s12967-022-03232-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Accepted: 01/05/2022] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND The prevalence of diffuse-type gastric cancer (GC), especially signet ring cell carcinoma (SRCC), has shown an upward trend in the past decades. This study aimed to develop computed tomography (CT) based radiomics nomograms to distinguish diffuse-type and SRCC GC preoperatively. METHODS A total of 693 GC patients from two centers were retrospectively analyzed and divided into training, internal validation and external validation cohorts. Radiomics features were extracted from CT images, and the Lauren radiomics model was established with a support vector machine (SVM) classifier to identify diffuse-type GC. The Lauren radiomics nomogram integrating radiomics features score (Rad-score) and clinicopathological characteristics were developed and evaluated regarding prediction ability. Further, the SRCC radiomics nomogram designed to identify SRCC from diffuse-type GC was developed and evaluated following the same procedures. RESULTS Multivariate analysis revealed that Rad-scores was significantly associated with diffuse-type GC and SRCC (p < 0.001). The Lauren radiomics nomogram showed promising prediction performance with an area under the curve (AUC) of 0.895 (95%CI, 0.957-0.932), 0.841 (95%CI, 0.781-0.901) and 0.893 (95%CI, 0.831-0.955) in each cohort. The SRCC radiomics nomogram also showed good discrimination, with AUC of 0.905 (95%CI,0.866-0.944), 0.845 (95%CI, 0.775-0.915) and 0.918 (95%CI, 0.842-0.994) in each cohort. The radiomics nomograms showed great model fitness and clinical usefulness by calibration curve and decision curve analysis. CONCLUSION Our CT-based radiomics nomograms had the ability to identify the diffuse-type and SRCC GC, providing a non-invasive, efficient and preoperative diagnosis method. They may help guide preoperative clinical decision-making and benefit GC patients in the future.
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Affiliation(s)
- Tao Chen
- Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, Guangdong, China.
| | - Jing Wu
- Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, Guangdong, China
| | - Chunhui Cui
- Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, Guangdong, China
| | - Qinglie He
- Department of The First Clinical Medical College, Southern Medical University, Guangzhou, 510515, China
| | - Xunjun Li
- Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, Guangdong, China
| | - Weiqi Liang
- Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, Guangdong, China
| | - Xiaoyue Liu
- School of Biomedical Engineering, Southern Medical University, Guangzhou, 510515, Guangdong Province, China
| | - Tianbao Liu
- School of Biomedical Engineering, Southern Medical University, Guangzhou, 510515, Guangdong Province, China
| | - Xuanhui Zhou
- Department of The First Clinical Medical College, Southern Medical University, Guangzhou, 510515, China
| | - Xifan Zhang
- Department of The First Clinical Medical College, Southern Medical University, Guangzhou, 510515, China
| | - Xiaotian Lei
- Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, Guangdong, China
| | - Wei Xiong
- Medical Imaging Center, Nanfang Hospital, Southern Medical University, No.1838, North Guangzhou Avenue, Guangzhou, 510515, Guangdong, China
| | - Jiang Yu
- Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, Guangdong, China
| | - Guoxin Li
- Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, Guangdong, China.
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Shiotsuki K, Takizawa K, Ono H. Indications of Endoscopic Submucosal Dissection for Undifferentiated Early Gastric Cancer: Current Status and Future Perspectives for Further Expansion. Digestion 2021; 103:76-82. [PMID: 34736250 DOI: 10.1159/000519650] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Accepted: 09/15/2021] [Indexed: 02/04/2023]
Abstract
BACKGROUND Endoscopic submucosal dissection (ESD) is a widely accepted and minimally invasive treatment for early gastric cancer (EGC) without the risk of lymph node metastasis (LNM). However, undifferentiated-type EGC (UD-EGC) is considered to have a relatively high risk of LNM. Recently, the Japan Clinical Oncology Group conducted a nonrandomized confirmatory trial (JCOG1009/1010) to evaluate the efficacy and safety of ESD for UD-EGC. Herein, we review the results of JCOG1009/1010 and the possibility of further expanding the indications for ESD. SUMMARY JCOG1009/1010 showed excellent technical results and 5-year overall survival in patients with UD-EGC. Based on the results, ESD for UD-EGC (cT1a) of ≤2 cm without ulceration was technically feasible and acceptable for standard treatment instead of gastrectomy with lymph node dissection. A review of the EGC of mixed histological type (mixed EGC) suggested that the mixed EGC might have worse biological behavior than the pure histological type. In cases of intramucosal EGC with pure signet-ring cell carcinoma or presenting a double-layer structure, the risk of LNM might be relatively low. Thus, there is a possibility of further expanding the indications or curative evaluations. In the case of UD-EGC after noncurative resection, the data suggest that the eCura system may be applicable to UD-EGC; however, due to the small number of cases, further study is warranted. Key Message: This review summarizes the present knowledge regarding indications for UD-EGC and the possibility of further expanding them.
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Affiliation(s)
- Kazuo Shiotsuki
- Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan
| | - Kohei Takizawa
- Department of Gastroenterology and Endoscopy, Sapporo Kinentou Hospital, Hokkaido, Japan
| | - Hiroyuki Ono
- Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan
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18
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Kumar NAN, Jose A, Usman N, Rajan K, Munisamy M, Shetty PS, Rao M. Signet ring cell cancer of stomach and gastro-esophageal junction: molecular alterations, stage-stratified treatment approaches, and future challenges. Langenbecks Arch Surg 2021; 407:87-98. [PMID: 34505199 PMCID: PMC8847240 DOI: 10.1007/s00423-021-02314-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Accepted: 08/23/2021] [Indexed: 12/27/2022]
Abstract
Purpose There has been an increase in the incidence of signet ring cell cancer (SRCC) of the stomach and gastro-esophageal junction (GEJ). The multistage carcinogenesis involving genetic and epigenetic aberrations may have a major role in the increasing incidence of SRCC. Although there are numerous studies on the prognostic value of SRCC, they are markedly inconsistent in their results, making it impossible to draw any meaningful conclusions. We aimed to examine the available evidences on molecular alterations and stage-stratified treatment approaches in SRCC of the stomach and GEJ. Methods A systematic search was carried out in PubMed. Studies available in English related to SRCC of stomach and gastro-esophageal junction were identified and evaluated. Results This study reviewed the current evidence and provided an insight into the molecular alterations, stage-stratified treatment approaches, and future challenges in the management of SRCC of the stomach and GEJ. Specific therapeutic strategies and personalized multimodal treatment have been recommended based on the tumor characteristics of SRCC. Conclusion Multistage carcinogenesis involving genetic and epigenetic aberrations in SRCC is interlinked with stage-dependent prognosis. Specific therapeutic strategy and personalized multimodal treatment should be followed based on the tumor characteristics of SRCC. Endoscopic resection, radical surgery, and perioperative chemotherapy should be offered in carefully selected patients based on stage and prognostic stratification. Future studies in genetic and molecular analysis, histopathological classification, and options of multimodality treatment will improve the prognosis and oncological outcomes in SRCC of gastric and GEJ.
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Affiliation(s)
- Naveena A N Kumar
- Department of Surgical Oncology, Manipal Comprehensive Cancer Care Center, Kasturba Medical College, Manipal Academy of Higher Education (MAHE), Manipal, Karnataka, 576104, India
| | - Anmi Jose
- Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education (MAHE), Manipal, Karnataka, 576104, India
| | - Nawaz Usman
- Department of Surgical Oncology, Manipal Comprehensive Cancer Care Center, Kasturba Medical College, Manipal Academy of Higher Education (MAHE), Manipal, Karnataka, 576104, India
| | - Keshava Rajan
- Department of Surgical Oncology, Manipal Comprehensive Cancer Care Center, Kasturba Medical College, Manipal Academy of Higher Education (MAHE), Manipal, Karnataka, 576104, India
| | - Murali Munisamy
- Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education (MAHE), Manipal, Karnataka, 576104, India
| | - Preethi S Shetty
- Department of Surgical Oncology, Manipal Comprehensive Cancer Care Center, Kasturba Medical College, Manipal Academy of Higher Education (MAHE), Manipal, Karnataka, 576104, India
| | - Mahadev Rao
- Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education (MAHE), Manipal, Karnataka, 576104, India.
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LncRNA FAM230B Promotes Gastric Cancer Growth and Metastasis by Regulating the miR-27a-5p/TOP2A Axis. Dig Dis Sci 2021; 66:2637-2650. [PMID: 32910366 DOI: 10.1007/s10620-020-06581-z] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2020] [Accepted: 08/21/2020] [Indexed: 12/11/2022]
Abstract
AIM Long non-coding RNAs serve as key components of competing endogenous RNA (ceRNA) networks that underlie tumorigenesis. We investigated the pathogenic roles of lncRNA FAM230B and its molecular mechanism in gastric cancer (GC). METHOD The levels of FAM230B expression in five gastric cancer cell lines and in human gastric mucosal cells were compared by quantitative RT-PCR. To analyze the function of FAM230B in GC, we overexpressed FAM230B in AGS cells, silenced FAM230B in MGC-803 cells, and tested the effect of FAM230B on tumor growth in nude mice. The interaction between miR-27a-5p and FAM230B was predicted by a bioinformatics analysis and then verified with a dual-luciferase reporter assay. We also further investigated the role and mechanism of FAM230B by forcing overexpression of miR-27a-5p in MGC-803 gastric cancer cells. RESULTS We found that FAM230B was highly expressed in gastric cancer cell lines and mainly located in the cytoplasm. FAM230B overexpression promoted the proliferation, migration, and invasion of AGS cells and repressed their apoptosis; it also facilitated tumor growth in vivo. In contrast, FAM230B knockdown suppressed the proliferation, migration, and invasion of MGC0803 cells, but enhanced their apoptosis and inhibited tumor growth in vivo. MiR-27a-5p expression was suppressed by FAM230B overexpression in AGS cells. MiR-27a-5p inhibited the proliferation, migration, and invasion of gastric cancer cells, and promoted the apoptosis of gastric cancer cells by reducing TOP2A (topoisomerase 2 alpha) expression. CONCLUSION Our study showed that lncRNA FAM230B might function to promote GC. FAM230B functioned as a ceRNA by sponging miR-27a-5p and enhancing TOP2A expression.
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20
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Zhao S, Lv L, Zheng K, Tian Y, Zheng JC, Jiang CG. Prognosis and Biological Behavior of Gastric Signet-Ring Cell Carcinoma Better or Worse: A Meta-Analysis. Front Oncol 2021; 11:603070. [PMID: 34277391 PMCID: PMC8278333 DOI: 10.3389/fonc.2021.603070] [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] [Received: 09/05/2020] [Accepted: 06/11/2021] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND The clinical pathology of gastric signet-ring cell carcinoma (SRC) is still unclear. This meta-analysis was performed to evaluate the difference in biological behavior and prognosis between SRC and non-signet ring cell carcinoma (NSRC). METHODS A total of 58 eligible studies were analyzed using RevMan and other auxiliary software. Biological behaviors were compared based on odds ratio (OR) and mean difference (MD). Hazards ratio (HR) was calculated for prognosis based on Kaplan-Meier curves. RESULTS Totally, 28,946 SRC patients were compared with 81,917 NSRC patients. Compared with NSRC patients, lower male: female ratio (OR = 0.53, P < 0.01), younger age (MD = -4.89, P < 0.01), more middle location (OR = 1.64, P < 0.01), more depressed type at early stage (OR = 1.31, P < 0.05), higher incidence of Borrmann type IV (OR = 1.96, P < 0.01), less lymph node metastasis at early stage (OR = 0.78, P < 0.05), better prognosis at early stage (HR = 0.59, P < 0.01), and worse prognosis at advanced stage (HR = 1.19, P < 0.01) were associated with SRC patients. CONCLUSION The prognosis of SRC at early stage is better than other types of gastric cancer, while that of SRC at advanced stage is relatively poorer.
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Affiliation(s)
- Shuai Zhao
- Department of Surgical Oncology and General Surgery, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Ling Lv
- Department of Thoracic Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Kai Zheng
- Department of Surgical Oncology and General Surgery, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Yu Tian
- Department of Surgical Oncology and General Surgery, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Jian-Chun Zheng
- Department of Surgical Oncology and General Surgery, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Cheng-Gang Jiang
- Department of Surgical Oncology and General Surgery, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, The First Affiliated Hospital of China Medical University, Shenyang, China
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21
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Togasaki K, Sugimoto S, Ohta Y, Nanki K, Matano M, Takahashi S, Fujii M, Kanai T, Sato T. Wnt Signaling Shapes the Histologic Variation in Diffuse Gastric Cancer. Gastroenterology 2021; 160:823-830. [PMID: 33217450 DOI: 10.1053/j.gastro.2020.10.047] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2020] [Revised: 10/28/2020] [Accepted: 10/28/2020] [Indexed: 01/08/2023]
Abstract
BACKGROUND AND AIMS Diffuse-type gastric cancer (GC) is currently subdivided into signet-ring cell carcinoma (SRCC) and non-SRCC, referred to as poorly cohesive carcinoma not otherwise specified (PCC-NOS). Although these subtypes are considered to be independent, they often coexist in the same tumors, raising a question of whether they clonally differ or not. To tackle this question, we established an experimental platform for human diffuse GC that enables accurate modeling of histologic subtypes. METHODS Seven patient-derived diffuse GC organoid lines were established, characterized by histopathologic analysis, in situ hybridization, and gene expression analysis. For genetic modeling of diffuse GC, we knocked out CDH1 and/or TP53 in human normal gastric organoids. Green fluorescent protein-labeled GC organoids were xenotransplanted into immune-deficient mice for in vivo assessment. RESULTS PCC-NOS organoids transformed into SRCC-like structures on removal of Wnt and R-spondin from the culture medium. This morphologic change paralleled downregulation of Wnt-target and gastric stem cell genes, including LGR5, and elevation of differentiation markers, such as KRT20 and MUCs. The association between Wnt target gene expression and histologic subtypes was confirmed in 3 patient-derived GC tissues. In vivo, single clone-derived organoids formed tumors that comprised 2 distinct histologic compartments, each corresponding to SRCC and PCC-NOS. The transition from PCC-NOS to SRCC histology reflected the abundance of surrounding R-spondin-expressing fibroblasts. CONCLUSIONS SRCC and PCC-NOS were clonally identical, and their morphology was regulated by extracellular Wnt and R-spondin expression. Our results decoded how genetic mutations and the tumor environment shape pathohistologic and biologic phenotypes in human diffuse GCs.
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Affiliation(s)
- Kazuhiro Togasaki
- Department of Organoid Medicine, Keio University School of Medicine, Tokyo, Japan; Department of Gastroenterology, Keio University School of Medicine, Tokyo, Japan
| | - Shinya Sugimoto
- Department of Organoid Medicine, Keio University School of Medicine, Tokyo, Japan; Department of Gastroenterology, Keio University School of Medicine, Tokyo, Japan
| | - Yuki Ohta
- Department of Organoid Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Kosaku Nanki
- Department of Organoid Medicine, Keio University School of Medicine, Tokyo, Japan; Department of Gastroenterology, Keio University School of Medicine, Tokyo, Japan
| | - Mami Matano
- Department of Organoid Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Sirirat Takahashi
- Department of Organoid Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Masayuki Fujii
- Department of Organoid Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Takanori Kanai
- Department of Gastroenterology, Keio University School of Medicine, Tokyo, Japan
| | - Toshiro Sato
- Department of Organoid Medicine, Keio University School of Medicine, Tokyo, Japan; Department of Gastroenterology, Keio University School of Medicine, Tokyo, Japan.
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22
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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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Lin CL, Zhu GW, Huang YJ, Zheng W, Yang SG, Ye JX. Operable gastric adenocarcinoma with different histological subtypes: Cancer-specific survival in the United States. Saudi J Gastroenterol 2020; 26:46-52. [PMID: 32031158 PMCID: PMC7045769 DOI: 10.4103/sjg.sjg_406_19] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND/AIMS Gastric signet ring cell carcinoma (GSRC), a subtype of adenocarcinoma, has been considered a histological type with poor survival. We aimed to compare the survival outcomes between patients with GSRC and patients with gastric non-signet ring cell adenocarcinoma (NGSRC) and constructed a nomogram to predict gastric adenocarcinoma-specific survival (GCSS). PATIENTS AND METHODS We identified 10,031 patients with gastric adenocarcinoma (GA) from the surveillance, epidemiology, and end results (SEER) database and stratified them into two histological type groups: GSRC and NGSRC. We used propensity score matching and identified 4304 patients (training cohort) to assess the effect of the histological type on GCSS with Kaplan-Meier curves, and constructed a predictive nomogram. The accuracy of the nomogram was tested on the remaining 5727 patients (validation cohort) with concordance index (C-index) values, calibration curves, and receiver operating characteristic (ROC) curve analysis. RESULTS We found that the histological type SRC was not associated with significantly poor survival (5-year survival rate: 46.1% vs 46.7%, P = 0.822). GSRC patients had similar GCSS rates compared to those with NGSRC in each tumor, node, and metastasis (TNM) stage (allP > 0.05). The nomogram showed that histological type was a relatively weak predictor of survival. The C-index value of the nomogram for predicting survival was 0.720, similar to that in the validation cohort (0.724). CONCLUSIONS Patients with GSRC had a similar prognosis to those with NGSRC. The proposed nomogram allowed a relatively accurate survival prediction for operable GA patients after gastrectomy.
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Affiliation(s)
- Chun-Lin Lin
- The First Affiliated Hospital of Fujian Medical University, Department of Gastrointestinal Surgery 2 Section, 20th,Chazhong Road, Fuzhou, Fujian, China
| | - Guang-Wei Zhu
- The First Affiliated Hospital of Fujian Medical University, Department of Gastrointestinal Surgery 2 Section, 20th,Chazhong Road, Fuzhou, Fujian, China
| | - Yong-Jian Huang
- The First Affiliated Hospital of Fujian Medical University, Department of Gastrointestinal Surgery 2 Section, 20th,Chazhong Road, Fuzhou, Fujian, China
| | - Wei Zheng
- The First Affiliated Hospital of Fujian Medical University, Department of Gastrointestinal Surgery 2 Section, 20th,Chazhong Road, Fuzhou, Fujian, China
| | - Shu-Gang Yang
- The First Affiliated Hospital of Fujian Medical University, Department of Gastrointestinal Surgery 2 Section, 20th,Chazhong Road, Fuzhou, Fujian, China
| | - Jian-Xin Ye
- The First Affiliated Hospital of Fujian Medical University, Department of Gastrointestinal Surgery 2 Section, 20th,Chazhong Road, Fuzhou, Fujian, China
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24
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Chen F, Jiang K, Han B. Diagnostic challenges of intra-operative frozen consultation for gastrointestinal signet ring cell carcinoma†. Histopathology 2020; 78:300-309. [PMID: 32767784 DOI: 10.1111/his.14229] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2020] [Accepted: 08/04/2020] [Indexed: 11/29/2022]
Abstract
AIMS Signet ring cell carcinoma (SRCC) is challenging to recognise on intra-operative frozen sections, with known high false-negative rates. The objective of this study was to investigate common factors contributing to discrepancies between intra-operative frozen diagnoses and those made upon review of permanent sections, and summarise our experiences gained and lessons learned on minimising errors on intra-operative frozen diagnoses of gastrointestinal SRCC. METHODS AND RESULTS We retrospectively examined our pathology database from 25 May 2000 to 1 January 2018 and re-reviewed intra-operative frozen sections and permanent haematoxylin and eosin (H&E) slides for specimens confirmed with SRCC on permanent sections. This study includes 83 specimens taken from 50 patients, with an accuracy of 85.5%. Main common factors causing discordance or deferral in recognising SRCC between intra-operative frozen procedures and permanent sections include: (i) resemblance of clusters of SRCC cells with a myxoid background; (ii) disguise as normal or reactive cells (histiocytes, macrophages, large reactive lymphocytes, plasma cells or adipocytes) due to their relatively clear or depleted cytoplasmic mucin; and (iii) histological sampling errors, leading to misses of small foci of SRCC on frozen section slides. CONCLUSIONS An accurate diagnosis of SRCC during intra-operative frozen consultations remains challenging. Based on our experiences and lessons, the most important strategies to reduce diagnostic errors are: (i) understanding the unusual histomorphological features of SRCC cells on frozen sections including, but not limited to, intracellular mucin depletion, absence of desmoplasia and no adjacent pre-cancer changes; and (ii) close attention to abrupt transition from normal architecture (e.g. glandular or submucosal loose connective tissue) to myxoid and/or inflammatory-like appearance, which potentially harbours SRCC.
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Affiliation(s)
- Fengming Chen
- Department of Pathology and Laboratory Medicine, Penn State Health Milton S. Hershey Medical Center, Hershey, PA, USA
| | - Kun Jiang
- Department of Pathology, Moffitt Cancer Center, Tampa, FL, USA.,Department of Oncologic Sciences, University of South Florida College of Medicine, Tampa, FL, USA
| | - Bing Han
- Department of Pathology and Laboratory Medicine, Penn State Health Milton S. Hershey Medical Center, Hershey, PA, USA
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Chu Y, Mao T, Li X, Jing X, Ren M, Huang Z, Zhou XB, Chen Y, Tian Z. Predictors of Lymph Node Metastasis and Differences Between Pure and Mixed Histologic Types of Early Gastric Signet-ring Cell Carcinomas. Am J Surg Pathol 2020; 44:934-942. [PMID: 32149737 PMCID: PMC7289133 DOI: 10.1097/pas.0000000000001460] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The aim of this study was to investigate predictors of lymph node metastasis (LNM) in early gastric signet-ring cell carcinoma (SRCC) and determine clinicopathologic and prognostic differences of different histologic subtypes. We retrospectively analyzed 13,661 gastric cancer patients; 231 were eligible for inclusion. Data for clinical, endoscopic, and histopathologic characteristics and prognoses were collected. Patients were followed up regarding postresection survival; overall and disease-specific survival rates were estimated by the Kaplan-Meier method with a log-rank test, and prognostic factors were evaluated by Cox regression. LNM incidence in early SRCC was 16.0% (37/231) overall: 6.9% (8/116) and 25.2% (29/115) in patients with pure and mixed SRCC, respectively. Univariate and multivariate analyses revealed SM2 invasion (odds ratio [OR]=5.070, P=0.003), lymphovascular invasion (LVI) (OR=14.876, P<0.001), pathologic pattern of mixed SRCC (OR=3.226, P=0.026), ulcer presence (OR=3.340, P=0.019) and lesion size over 20 mm (OR=2.823, P=0.015) as independent risk factors for LNM. Compared with pure SRCC, the mixed subtype was associated with older age, larger lesion size, higher LVI frequency, more frequent perineural invasion, and most importantly, higher LNM incidence. Patients with pure SRCC showed significantly longer overall survival (P=0.004) and disease-specific survival (P=0.002) than mixed SRCC patients. Pathologic subtype (hazard ratio [HR]=3.682; P=0.047), age (HR=5.246; P=0.001), SM1 invasion (HR=6.192; P=0.023), SM2 invasion (HR=7.529; P=0.021) and LNM (HR=5.352; P<0.001) were independent prognostic factors. Independent risk factors for LNM in early gastric SRCC were SM2 invasion, LVI, pathologic pattern, ulcer presence and lesion size over 20 mm. Early SRCC should be further classified by the purity of the SRC component.
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Affiliation(s)
| | - Tao Mao
- Departments of Gastroenterology
| | | | | | | | | | - Xiao-Bin Zhou
- Department of Epidemiology and Health Statistics, School of Public Health, Qingdao University, Qingdao, Shandong Province, China
| | - Yunqing Chen
- Pathology, The Affiliated Hospital of Qingdao University
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The Clinicopathological Characteristics And Genetic Alterations of Signet-ring Cell Carcinoma in Gastric Cancer. Cancers (Basel) 2020; 12:cancers12082318. [PMID: 32824568 PMCID: PMC7463705 DOI: 10.3390/cancers12082318] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2020] [Revised: 08/04/2020] [Accepted: 08/12/2020] [Indexed: 02/08/2023] Open
Abstract
Signet-ring cell carcinoma (SRC) in advanced gastric cancer (GC) is often associated with more invasiveness and a worse prognosis than other cell types. The genetic alterations associated with gastric carcinogenesis in SRC are still unclear. In this study, 441 GC patients receiving curative surgery for GC between 2005 and 2013 were enrolled. The clinicopathological characteristics and genetic alterations of GC patients with and without SRC were compared. Among the 441 GC patients, 181 had SRC. For early GC, patients with SRC had more tumors located in the middle and lower stomach, more infiltrating tumors and better overall survival (OS) rates than those without SRC. For advanced GC, patients with SRC had more scirrhous type tumors, more PIK3CA amplifications, fewer microsatellite instability-high (MSI-H) tumors, more peritoneal recurrences and worse 5-year OS rates than those without SRC. For advanced GC with SRC, patients with peritoneal recurrence tended to have PD-L1 expression. For advanced GC without SRC, patients with liver metastasis tended to have PD-L1 expression, PI3K/AKT pathway mutations, TP53 mutations and MSI-H tumors. For advanced GC, PD-L1 expression was associated with peritoneal recurrence in SRC tumors, while non-SRC tumors with liver metastasis were likely to have PI3K/AKT pathway mutations, TP53 mutations and PD-L1 expression; immunotherapy and targeted therapy may be beneficial for these patients.
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Kim JS, Kang SH, Moon HS, Lee ES, Kim SH, Sung JK, Lee BS, Jeong HY. Accuracy of endoscopic size measurements of early gastric signet ring cell carcinoma. Surg Endosc 2020; 35:2324-2331. [PMID: 32430526 DOI: 10.1007/s00464-020-07646-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2019] [Accepted: 05/13/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIMS Indications for endoscopic submucosal dissection (ESD) of early gastric cancer (EGC) are expanding, but signet ring cell carcinoma (SRC) is still unclear because of its unclear boundaries. The purpose of this study was to compare pathologic size and endoscopic size in SRC-type EGC and to find risk factors associated with tumor size underestimation. METHODS Medical records of 137 patients diagnosed with SRC-type EGC between January 2009 and December 2016 at our tertiary hospital were reviewed. According to pathologic and endoscopic tumor sizes, they were classified into correct estimation, underestimation, and overestimation groups, and risk factors related to underestimation were analyzed. RESULTS Among 137 patients with SRC-type EGC, 77 patients (56.2%) had undergone correct estimation, 43 patients (31.4%) had undergone underestimation, and 17 patients (12.4%) had undergone overestimation. Mean pathologic size (SD) was 20.1 (13.8) mm and mean endoscopic size (SD) was 17.9 (10.1) mm, the correlation coefficients were 0.919 (p < 0.001) , and there was no significant difference between the two groups. Multivariate analysis showed that tumor size more than 20 mm (OR 3.419; 95% CI 1.271-9.194; p = 0.015) and atrophy (OR 6.011; 95% CI 2.311-15.633; p = 0.001) were risk factors for tumor size underestimation. CONCLUSION There was no significant difference in pathologic and endoscopic size in SRC-type EGC. Therefore, ESD may be considered as a therapeutic option if the size of the tumor is less than 20 mm and atrophy is not present in the surrounding mucosa.
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Affiliation(s)
- Ju Seok Kim
- Department of Internal Medicine, Chungnam National University School of Medicine, 282 Munhwa-ro, Jung-gu, Daejeon, 35015, Korea
| | - Sun Hyung Kang
- Department of Internal Medicine, Chungnam National University School of Medicine, 282 Munhwa-ro, Jung-gu, Daejeon, 35015, Korea.
| | - Hee Seok Moon
- Department of Internal Medicine, Chungnam National University School of Medicine, 282 Munhwa-ro, Jung-gu, Daejeon, 35015, Korea
| | - Eaum Seok Lee
- Department of Internal Medicine, Chungnam National University School of Medicine, 282 Munhwa-ro, Jung-gu, Daejeon, 35015, Korea
| | - Seok Hyun Kim
- Department of Internal Medicine, Chungnam National University School of Medicine, 282 Munhwa-ro, Jung-gu, Daejeon, 35015, Korea
| | - Jae Kyu Sung
- Department of Internal Medicine, Chungnam National University School of Medicine, 282 Munhwa-ro, Jung-gu, Daejeon, 35015, Korea
| | - Byung Seok Lee
- Department of Internal Medicine, Chungnam National University School of Medicine, 282 Munhwa-ro, Jung-gu, Daejeon, 35015, Korea
| | - Hyun Yong Jeong
- Department of Internal Medicine, Chungnam National University School of Medicine, 282 Munhwa-ro, Jung-gu, Daejeon, 35015, Korea
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Altay SB, Akkurt G, Yılmaz N, Özdemir N. Clinicopathological Evaluation of Gastric Signet Ring Cell Carcinoma: Our Experience. Euroasian J Hepatogastroenterol 2020; 10:76-84. [PMID: 33511069 PMCID: PMC7801891 DOI: 10.5005/jp-journals-10018-1325] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Aim Gastric cancer is one of the most common cancers worldwide. In Turkey, stomach cancer is ranked 5th among men and 8th among women in all cancers and is located in the forefront in cancer-related deaths. Signet ring cell adenocarcinoma, which is the histopathological subtype of gastric cancer, has a poor prognosis. The incidence of signet ring cell adenocarcinoma is rising. In the present study, we aimed to describe the clinicopathologic features of signet ring cell adenocarcinoma. Materials and Methods A total of 79 patients with 30 being female (38%) and 49 male (62%) who were diagnosed with gastric signet ring cell adenocarcinoma in the Medical Oncology Department of Ankara Numune Training and Research Hospital between January 2004 and October 2015 were retrospectively evaluated. Results The baseline demographic characteristics of the patients, such as tumor localization, tumor stage, preoperative serum tumor markers, and treatment type (surgery and chemotherapy regimen), and the effects of these variables on survival and mortality were evaluated. Total surgery, stage III disease, moderate to poor grade, preoperative serum CA 19-9 and CEA levels were found as independent predictors of progression risk (p < 0.05). Each 1 ng/mL increase in preoperative serum CEA level was found to increase the risk of progression by 1.20 folds. Again, each 1 U/mL in preoperative serum CA 19-9 level was found to increase the risk of progression and mortality by 1.06 folds. Conclusion The clinicopathologic features of signet ring cell stomach cancer were described. Tumor localization and disease, CA 19-9 and CEA levels, and treatment type (surgery and chemotherapy regimen) were effective on survival and mortality. However, further studies with larger patient groups are needed on this issue. How to cite this article Altay SB, Akkurt G, Yılmaz N, et al. Clinicopathological Evaluation of Gastric Signet Ring Cell Carcinoma: Our Experience. Euroasian J Hepato-Gastroenterol 2020;10(2):76–84.
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Affiliation(s)
- Sevgi B Altay
- Department of Internal Medicine, Gaziantep 25 Aralık State Hospital, Gaziantep, Turkey
| | - Gökhan Akkurt
- Department of General Surgery, Kecioren Training and Research Hospital, Ankara, Turkey
| | - Nisbet Yılmaz
- Department of Internal Medicine, Ankara City Hospital, Ankara, Turkey
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Kerckhoffs KGP, Liu DHW, Saragoni L, van der Post RS, Langer R, Bencivenga M, Iglesias M, Gallo G, Hewitt LC, Fazzi GE, Vos AM, Renaud F, Yoshikawa T, Oshima T, Tomezzoli A, de Manzoni G, Arai T, Kushima R, Carneiro F, Grabsch HI. Mucin expression in gastric- and gastro-oesophageal signet-ring cell cancer: results from a comprehensive literature review and a large cohort study of Caucasian and Asian gastric cancer. Gastric Cancer 2020; 23:765-779. [PMID: 32488651 PMCID: PMC7438382 DOI: 10.1007/s10120-020-01086-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Accepted: 05/14/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND The literature on the prognostic relevance of signet-ring cell (SRC) histology in gastric cancer (GC) is controversial which is most likely related to inconsistent SRC classification based on haematoxylin-eosin staining. We hypothesised that mucin stains can consistently identify SRC-GC and predict GC patient outcome. METHODS We performed a comprehensive literature review on mucin stains in SRC-GC and characterised the mucin expression in 851 Caucasian GC and 410 Asian GC using Alcian Blue (AB)-Periodic Acid-Schiff (PAS), MUC2 (intestinal-type mucin), and MUC5AC (gastric-type mucin). The relationship between mucin expression and histological phenotype [poorly cohesive (PC) including proportion of SRCs, non-poorly cohesive (non-PC), or mucinous (MC)], clinicopathological variables, and patient outcome was analysed. RESULTS Depending on mucin expression and cut-offs, the positivity rates of SRC-GC reported in the literature varied from 6 to 100%. Patients with MUC2 positive SRC-GC or SRC-GC with (gastro)intestinal phenotype had poorest outcome. In our cohort study, PC with ≥ 10% SRCs expressed more frequently MUC2, MUC5AC, and ABPAS (p < 0.001, p = 0.004 and p < 0.001, respectively). Caucasians with AB positive GC or combined ABPAS-MUC2 positive and MUC5AC negative had poorest outcome (all p = 0.002). This association was not seen in Asian patients. CONCLUSIONS This is the first study to suggest that mucin stains do not help to differentiate between SRC-GC and non-SRC-GC. However, mucin stains appear to be able to identify GC patients with different outcome. To our surprise, the relationship between outcome and mucin expression seems to differ between Caucasian and Asian GC patients which warrants further investigations.
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Affiliation(s)
- K G P Kerckhoffs
- Department of Pathology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center+, P. Debyelaan 25, 6229HX, Maastricht, The Netherlands
| | - D H W Liu
- Department of Pathology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center+, P. Debyelaan 25, 6229HX, Maastricht, The Netherlands
| | - L Saragoni
- Pathology Unit, Morgagni-Pierantoni Hospital, Forlì, Italy
| | | | - R Langer
- Institute of Pathology, University of Bern, Bern, Switzerland
| | - M Bencivenga
- Unit of General and Upper GI Surgery , University of Verona, Verona, Italy
| | - M Iglesias
- Pathology Department, Hospital del Mar, Universitat Autonoma de Barcelona, Barcelona, Spain
| | - G Gallo
- Department of Anatomic Pathology, Azienda Ospedaliero-Universitaria Policlinico di Modena, Modena, Italy
| | - L C Hewitt
- Department of Pathology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center+, P. Debyelaan 25, 6229HX, Maastricht, The Netherlands
| | - G E Fazzi
- Department of Pathology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center+, P. Debyelaan 25, 6229HX, Maastricht, The Netherlands
| | - A M Vos
- Department of Pathology, Radboudumc, Nijmegen, The Netherlands
| | - F Renaud
- Department of Pathology, Univ. Lille, CNRS, Inserm, CHU Lille, UMR9020 - UMR-S 1277 - Canther - Cancer Heterogeneity, Plasticity and Resistance to Therapies, Lille, France
| | - T Yoshikawa
- Department of Gastric Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - T Oshima
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan
| | - A Tomezzoli
- Department of Pathology, Verona University Hospital, Verona, Italy
| | - G de Manzoni
- Unit of General and Upper GI Surgery , University of Verona, Verona, Italy
| | - T Arai
- Department of Pathology, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, Japan
| | - R Kushima
- Department of Pathology, Shiga University of Medical Science, Shiga, Japan
| | - F Carneiro
- Institute of Molecular Pathology and Immunology at the University of Porto (Ipatimup), Porto, Portugal
- Instituto de Investigação e Inovação em Saúde (i3S), University of Porto, Porto, Portugal
- Pathology Department, Centro Hospitalar de São João and Faculty of Medicine, Porto, Portugal
| | - H I Grabsch
- Department of Pathology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center+, P. Debyelaan 25, 6229HX, Maastricht, The Netherlands.
- Division of Pathology and Data Analytics, Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK.
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Yoshida K, Mikami T, Oyama T, Sato Y, Saito T, Mikami T, Itabashi C, Soma Y, Fukuda S. Signet-ring Cell Carcinoma in Hyperplastic Polyp of the Stomach. Intern Med 2019; 58:3531-3535. [PMID: 31462587 PMCID: PMC6949455 DOI: 10.2169/internalmedicine.2860-19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
Signet-ring cell carcinoma rarely occurs in gastric hyperplastic polyps, with only a few such cases reported. We treated a 76-year-old woman with a signet-ring cell carcinoma arising from a hyperplastic polyp. She had been diagnosed with a gastric hyperplastic polyp four years previously. A follow-up endoscopic examination revealed the lesion in the polyp. A biopsy showed signet-ring cell carcinoma. Hybrid endoscopic submucosal dissection with snaring and a histological examination revealed signet-ring cell carcinoma in a hyperplastic polyp. The polyp was completely excised, with no evidence of recurrence one year later. A hyperplastic polyp of the stomach may transform into adenocarcinoma of an undifferentiated type.
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Affiliation(s)
- Kenta Yoshida
- Department of Internal Medicine, Kuroishi General Hospital, Japan
- Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, Japan
| | - Tatsuya Mikami
- Division of Endoscopy, Hirosaki University Hospital, Japan
| | - Takao Oyama
- Department of Internal Medicine, Kuroishi General Hospital, Japan
- Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, Japan
| | - Yuki Sato
- Department of Internal Medicine, Kuroishi General Hospital, Japan
| | - Taro Saito
- Department of Internal Medicine, Kuroishi General Hospital, Japan
| | - Takafumi Mikami
- Department of Internal Medicine, Kuroishi General Hospital, Japan
| | | | - Yasushi Soma
- Department of Internal Medicine, Kuroishi General Hospital, Japan
| | - Shinsaku Fukuda
- Department of Internal Medicine, Kuroishi General Hospital, Japan
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Wei F, Lyu H, Wang S, Chu Y, Chen F. Postoperative Radiotherapy Improves Survival in Gastric Signet-Ring Cell Carcinoma: a SEER Database Analysis. J Gastric Cancer 2019; 19:393-407. [PMID: 31897342 PMCID: PMC6928086 DOI: 10.5230/jgc.2019.19.e36] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2019] [Revised: 09/23/2019] [Accepted: 09/26/2019] [Indexed: 12/11/2022] Open
Abstract
PURPOSE To identify the potential therapeutic role of postoperative radiotherapy (RT) in patients with locally advanced (stage II and stage III) gastric signet ring cell carcinoma (SRC). MATERIALS AND METHODS Patients with locally advanced gastric SRC from the Surveillance, Epidemiology, and End Results program database between 2004 and 2012 were included in our study. Univariate and multivariate Cox proportional models were performed, and survival curves were generated to evaluate the prognostic effect of postoperative RT and surgery alone on SRC patients. Propensity score matching (PSM) was used to avoid selection bias among the study cohorts. RESULTS We found that patients with postoperative RT had better probability of survival compared with those who did not receive RT (overall survival [OS], P<0.001; cancer-specific survival [CSS], P<0.001). After PSM, analysis of both overall and CSS showed that patients who underwent postoperative RT had better prognosis than those receiving surgery alone in the matched cohort (OS, P=0.00079; CSS, P=0.0036). Multivariate Cox proportional model indicated that postoperative RT had better effect on prognosis compared with surgery alone with respect to both overall (hazard ratio [HR], 0.716; 95% confidence interval [95% CI], 0.590-0.87; P=0.001) and CSS (HR, 0.713; 95% CI, 0.570-0.890; P=0.003). CONCLUSIONS Postoperative RT had better prognosis compared with surgery alone for both overall and CSS for patients with locally advanced gastric SRC.
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Affiliation(s)
- Feng Wei
- Department of Gastroenterology, The Fifth People's Hospital of Shanghai Fudan University, Shanghai, China
| | - Hongwei Lyu
- Department of Gastroenterology, The Fifth People's Hospital of Shanghai Fudan University, Shanghai, China
| | - Shuoer Wang
- Central Laboratory, The Fifth People's Hospital of Shanghai Fudan University, Shanghai, China
| | - Yan Chu
- Department of Gastroenterology, The Fifth People's Hospital of Shanghai Fudan University, Shanghai, China
| | - Fengyuan Chen
- Department of Gastroenterology, The Fifth People's Hospital of Shanghai Fudan University, Shanghai, China
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Risk Factors for Lymph Node Metastasis in Undifferentiated Early Gastric Cancer. Indian J Surg 2019. [DOI: 10.1007/s12262-018-1850-0] [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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Ryu DG, Choi CW, Kim SJ, Kang DH, Kim HW, Park SB, Nam HS. Possible indication of endoscopic resection in undifferentiated early gastric cancer. Sci Rep 2019; 9:16869. [PMID: 31728024 PMCID: PMC6856523 DOI: 10.1038/s41598-019-53374-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2019] [Accepted: 10/26/2019] [Indexed: 12/20/2022] Open
Abstract
Endoscopic resection for early gastric cancer (EGC) without lymph node metastasis may be a valuable treatment option. To date, endoscopic resection for undifferentiated EGC is being investigated. We evaluated the risk of lymph node metastasis in undifferentiated EGC by examining the preoperative endoscopic findings and operated pathologic specimen. The medical records of patients who underwent surgical resection because of undifferentiated EGC between November 2008 and December 2015 were reviewed retrospectively. The risk factors associated with lymph node metastasis and the lymph node metastasis rate in the expanded indication of undifferentiated EGC were evaluated. A total of 376 patients with undifferentiated EGC (233 signet ring cell type and 143 poorly differentiated type) were analyzed. Lymph node metastasis was found in 9.8% of the patients. Among the patients who met the expanded criteria (59 patients), only one patient had lymph node metastasis (signet ring cell type without ulceration and 15 mm in size). The risk factors associated with lymph node metastasis were lesion size >20 mm (OR 3.013), scar deformity (OR 2.248), surface depression (OR 2.360), submucosal invasion (OR 3.427), and lymphovascular invasion (OR 6.296). Before endoscopic resection of undifferentiated EGC, careful selection of patients should be considered. The undifferentiated EGC with size ≥15 mm, scar deformity, surface depression, submucosal invasion, and lymphovascular invasion should be considered surgical resection instead of endoscopic resection.
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Affiliation(s)
- Dae Gon Ryu
- Department of Internal Medicine, Pusan National University School of Medicine and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Cheol Woong Choi
- Department of Internal Medicine, Pusan National University School of Medicine and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea.
| | - Su Jin Kim
- Department of Internal Medicine, Pusan National University School of Medicine and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Dae Hwan Kang
- Department of Internal Medicine, Pusan National University School of Medicine and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Hyung Wook Kim
- Department of Internal Medicine, Pusan National University School of Medicine and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Su Bum Park
- Department of Internal Medicine, Pusan National University School of Medicine and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Hyeong Seok Nam
- Department of Internal Medicine, Pusan National University School of Medicine and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea
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Expanding the indication of endoscopic submucosal dissection for undifferentiated early gastric cancer is safe or not? Asian J Surg 2019; 43:526-531. [PMID: 31706922 DOI: 10.1016/j.asjsur.2019.08.006] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2019] [Revised: 07/03/2019] [Accepted: 08/18/2019] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Endoscopic submucosal dissection (ESD) has gained more popularity in the treatment of early gastric cancer (EGC). Although there is a lack of confirmed evidence for the feasibility of ESD for undifferentiated EGC. The aim of the study was to investigate the feasibility of ESD with expanded indications for undifferentiated EGC patients. METHODS Data from patients with undifferentiated EGC (including signet-ring cell carcinoma, mucinous adenocarcinoma, mixed adenocarcinoma, and poorly differentiated adenocarcinoma) who underwent radical surgical resection were retrospectively reviewed. The relationship between the clinical parameters and the incidence of lymph node metastasis (LNM) was investigated. RESULTS A total of 517 patients were included in this study. The results showed that LNM was significantly associated with ulceration, tumor size, depth of invasion, lymphatic invasion, vascular invasion, and perineural invasion. Multivariate stepwise logistic regression analysis revealed that tumor size (OR = 1.61, 95% CI = 1.03-2.52, P = 0.0367), depth of tumor invasion (OR = 2.77, 95% CI = 1.66-4.63, P = 0.0001), and lymphatic invasion (OR = 14.74, 95% CI = 1.58-137.36, P = 0.0182) were independent risk factors for LNM. In the patients who would be included under the new proposed guidelines for ESD, including men with mucosal tumors ≤2 cm and without ulceration or lymphatic or venous infiltration, LNM was present in 11.9% (14/118). CONCLUSION Caution to be exercised in expanding application of ESD should be carefully weighed in undifferentiated EGC.
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Murai K, Takizawa K, Shimoda T, Fujii S, Sugino T, Yoshida M, Kawata N, Tanaka M, Kakushima N, Terashima M, Ono H. Effect of double-layer structure in intramucosal gastric signet-ring cell carcinoma on lymph node metastasis: a retrospective, single-center study. Gastric Cancer 2019; 22:751-758. [PMID: 30523555 DOI: 10.1007/s10120-018-00905-9] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2018] [Accepted: 11/25/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND Among all types of gastric cancer (GC), signet-ring cell carcinoma (sig-GC) accounts for 4-17% of cases. The prognosis of early sig-GC is relatively good, with the 5-year survival rate at 99.7%. However, the correlation between histological features and lymph node metastasis (LNM) among pT1a (M) sig-GC remains unclear. Sig-GC often exhibits a double-layer structure (DLS) in the intramucosal layer, demonstrating functional differentiation into the normal gastric gland. Assumedly, the loss of the differentiation makes the DLS deranged, accounting for the occurrence of submucosal invasion and LNM. This study aimed to assess the proportion of DLS, to elucidate the correlation between histological features (including DLS) and LNM status, and to determine the LNM-negative condition in pT1a (M) sig-GC. METHODS We reviewed the pathological data of 310 patients with 310 intramucosal sig-GCs who received gastrectomy with lymph node dissection. Immunohistochemistry was performed on all specimens to evaluate the presence of DLS. Furthermore, we review the clinicopathological features, including tumor size, lymphovascular invasion (LVI), ulceration (UL), and DLS results, and then statistically analyze the correlation between these features and LNM status. RESULTS Overall, 129 pT1a (M) sig-GCs (42%) were DLS present. The univariate analysis revealed that "Tumor size > 20 mm", "UL present", and "DLS absent" were significant risk factors of LNM. The multivariate logistic regression analysis revealed only "DLS absent" as statistically significant. CONCLUSIONS "DLS absent" is a risk factor of LNM detected by the multivariate analysis. In pT1a (M), LVI absent, UL absent, tumor size > 20 mm, sig-GC, no LNM occurred in "DLS present" cases.
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Affiliation(s)
- Katsuyuki Murai
- Division of Pathology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi, Suntogun, Shizuoka, 411-8777, Japan
- Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan
| | - Kohei Takizawa
- Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan
| | - Tadakazu Shimoda
- Division of Pathology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi, Suntogun, Shizuoka, 411-8777, Japan.
| | - Shougo Fujii
- Division of Pathology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi, Suntogun, Shizuoka, 411-8777, Japan
| | - Takashi Sugino
- Division of Pathology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi, Suntogun, Shizuoka, 411-8777, Japan
| | - Masao Yoshida
- Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan
| | - Noboru Kawata
- Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan
| | - Masaki Tanaka
- Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan
| | - Naomi Kakushima
- Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan
| | | | - Hiroyuki Ono
- Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan
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Perrot-Applanat M, Vacher S, Pimpie C, Chemlali W, Derieux S, Pocard M, Bieche I. Differential gene expression in growth factors, epithelial mesenchymal transition and chemotaxis in the diffuse type compared with the intestinal type of gastric cancer. Oncol Lett 2019; 18:674-686. [PMID: 31289541 PMCID: PMC6546989 DOI: 10.3892/ol.2019.10392] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2018] [Accepted: 03/21/2019] [Indexed: 12/17/2022] Open
Abstract
Gastric cancer (GC) is a highly heterogeneous disease and one of the major causes of cancer-related mortality worldwide. Diffuse-type gastric adenocarcinoma (or poorly cohesive- with independent cells) is characterized by aggressive behavior (rapid invasion, chemoresistance and peritoneal metastasis), as compared with intestinal-subtype adenocarcinoma. Diffuse subtype GC additionally has a substantially increasing incidence rate in Europe and the USA, and was often associated with younger age. Our objective was to analyze the expression and clinical significance of genes involved in several signaling pathways in diffuse-type GC. Tumors samples and non-malignant gastric tissues were obtained from patients with GC (diffuse-type and intestinal-subtype adenocarcinoma). The expression of 33 genes coding for proteins involved in four categories, growth factors and receptors, epithelial-mesenchymal transition, cell proliferation and migration, and angiogenesis was determined by reverse transcription-quantitative polymerase chain reaction. The expression of 22 genes was significantly upregulated in diffuse-type GC and two were downregulated (including CDH1) compared with normal tissues. Among these genes, acompared with intestinal-subtype adenocarcinoma, diffuse-type GC revealed elevated levels of IGF1 and IGF1R, FGF7 and FGFR1, ZEB2, CXCR4, CXCL12 and RHOA, and decreased levels of CDH1, MMP9 and MKI67. The expression of selected genes was compared with other genes and according to clinical parameters. Furthermore, TGF-β expression was significantly increased in linitis, a sub-population of diffusely infiltrating type associated with extensive fibrosis and tumor invasion. Our study identified new target genes (IGF1, FGF7, CXCR4, TG-β and ZEB2) whose expression is associated with aggressive phenotype of diffuse-type GC.
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Affiliation(s)
- Martine Perrot-Applanat
- INSERM U965, Lariboisiere Hospital, University of Paris-Diderot-Paris 7, 75010 Paris, France
| | - Sophie Vacher
- Department of Genetics, Pharmacogenomics Unit-Institut Curie, University of Paris-Descartes-Paris 5, 75005 Paris, France
| | - Cynthia Pimpie
- INSERM U965, Lariboisiere Hospital, University of Paris-Diderot-Paris 7, 75010 Paris, France
| | - Walid Chemlali
- Department of Genetics, Pharmacogenomics Unit-Institut Curie, University of Paris-Descartes-Paris 5, 75005 Paris, France
| | - Simon Derieux
- Department of Digestive and Oncology Surgery-Lariboisiere Hospital, University of Paris-Diderot-Paris 7, 75010 Paris, France
| | - Marc Pocard
- INSERM U965, Lariboisiere Hospital, University of Paris-Diderot-Paris 7, 75010 Paris, France
- Department of Digestive and Oncology Surgery-Lariboisiere Hospital, University of Paris-Diderot-Paris 7, 75010 Paris, France
| | - Ivan Bieche
- Department of Genetics, Pharmacogenomics Unit-Institut Curie, University of Paris-Descartes-Paris 5, 75005 Paris, France
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Machlowska J, Pucułek M, Sitarz M, Terlecki P, Maciejewski R, Sitarz R. State of the art for gastric signet ring cell carcinoma: from classification, prognosis, and genomic characteristics to specified treatments. Cancer Manag Res 2019; 11:2151-2161. [PMID: 30936747 PMCID: PMC6421895 DOI: 10.2147/cmar.s188622] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
Gastric cancer (GC) is responsible for 9% of cancer deaths worldwide. Over 950,000 new cases are diagnosed each year, and about 90% of them are in advanced stage, requiring chemotherapy. In Europe there has been research based on pre- and postoperative chemotherapy treatment, using 5-fluorouracil, epirubicin, cisplatin, capecitabine, and docetaxel. Chemotherapy significantly impairs the quality of life of patients; however, the final effects are not always satisfactory. There is scientific evidence that gastric mucus tumors and signet ring cell carcinomas have a pattern of specific signatures, that distinguish them from other gastric cancer subtypes, and may be associated with a poor response to systematic treatment. Signet ring cell carcinoma is less chemosensitive than others, and the increase in the percentage of signet ring cells correlates with resistance to chemotherapy. Perioperative chemotherapy in advanced signet ring cell carcinomas is an independent factor of poor prognosis and survival, which is explained by the toxicity of neoadjuvant treatment. Therefore, curative surgical resection enhanced by standardized lymphadenectomy remains the recommended gold standard in GC therapy. According to presented studies, early detection and aggressive treatments for this subtype of GC is a reasonable approach. This review paper is mostly addressed to physicians who are interested in updating to the state of the art concerning different subtypes of gastric carcinoma.
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Affiliation(s)
- Julita Machlowska
- Department of Human Anatomy, Medical University of Lublin, Lublin, Poland,
| | - Małgorzata Pucułek
- Department of Human Anatomy, Medical University of Lublin, Lublin, Poland,
| | - Monika Sitarz
- Department of Conservative Dentistry and Endodontics, Medical University of Lublin, Lublin, Poland
| | - Paweł Terlecki
- Department of Surgery, St. John's Cancer Center, Lublin, Poland,
| | | | - Robert Sitarz
- Department of Human Anatomy, Medical University of Lublin, Lublin, Poland,
- Department of Surgery, St. John's Cancer Center, Lublin, Poland,
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Kao YC, Fang WL, Wang RF, Li AFY, Yang MH, Wu CW, Shyr YM, Huang KH. Clinicopathological differences in signet ring cell adenocarcinoma between early and advanced gastric cancer. Gastric Cancer 2019; 22:255-263. [PMID: 30069742 DOI: 10.1007/s10120-018-0860-8] [Citation(s) in RCA: 59] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2018] [Accepted: 07/27/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND Signet ring cell adenocarcinoma is a histological classification based on the WHO classification. The presence of this specific histological type is associated with a worse pathological appearance. The prognosis of signet ring cell adenocarcinoma in gastric cancer patients after curative surgery is still under debate. METHODS From January 1988 to December 2012, a total of 2971 patients, including 819 early and 2152 advanced gastric cancer patients underwent curative resection for gastric cancer. Among them, there were 185 cases of signet ring cell adenocarcinoma in early gastric cancer patients, while there were 570 cases in advanced gastric cancer patients. RESULTS The overall incidence of signet ring cell adenocarcinoma was 25.4%. Our results showed that the 5-year overall survival rates of early gastric cancer patients with signet ring cell adenocarcinoma and non-signet ring cell adenocarcinoma were 90.7 and 83.2%, respectively (P = 0.001). The 5-year disease-free survival rates of early gastric cancer patients with signet ring cell adenocarcinoma and non-signet ring cell adenocarcinoma were 87.4 and 81.6%, respectively (P = 0.003). The 5-year overall survival rates of advanced gastric cancer patients with signet ring cell adenocarcinoma and non-signet ring cell adenocarcinoma were 32.1 and 37.9%, respectively (P = 0.041). The 5-year disease-free survival rates of advanced gastric cancer patients with signet ring cell adenocarcinoma and non-signet ring cell adenocarcinoma were 28.6 and 35.2%, respectively (P = 0.037). Signet ring cell adenocarcinoma was an independent predictor for overall survival in advanced gastric cancer (P = 0.017). CONCLUSION The clinical features and prognosis of signet ring cell adenocarcinoma are different between early and advanced gastric cancer. Signet ring cell adenocarcinoma is a poor prognostic factor in advanced gastric cancer after curative resection.
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Affiliation(s)
- Yi-Chu Kao
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Rd., Beitou District, Taipei City, 11217, Taiwan.,School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Wen-Liang Fang
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Rd., Beitou District, Taipei City, 11217, Taiwan.,School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Ruei-Fang Wang
- Department of Emergency Medicine, Taipei City Hospital, Ren-Ai Branch, Taipei, Taiwan
| | - Anna Fen-Yau Li
- School of Medicine, National Yang-Ming University, Taipei, Taiwan.,Department of Pathology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Muh-Hwa Yang
- School of Medicine, Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.,Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Chew-Wun Wu
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Rd., Beitou District, Taipei City, 11217, Taiwan.,School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Yi-Ming Shyr
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Rd., Beitou District, Taipei City, 11217, Taiwan.,School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Kuo-Hung Huang
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Rd., Beitou District, Taipei City, 11217, Taiwan. .,School of Medicine, Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
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Hu Q, Dekusaah R, Cao S, Pang T, Wang Y, Zhang B, Lv Y, Zhang X, Ling T, Zhuge Y, Wang L, Zou X, Zhang W, Huang Q, Xu G. Risk Factors of Lymph Node Metastasis in Patients with Early Pure and Mixed Signet Ring Cell Gastric Carcinomas. J Cancer 2019; 10:1124-1131. [PMID: 30854120 PMCID: PMC6400689 DOI: 10.7150/jca.29245] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2018] [Accepted: 01/02/2019] [Indexed: 01/15/2023] Open
Abstract
Background: Early gastric carcinoma (EGC) with pure signet ring cell carcinoma (pSRCC) has been reported to have favourable prognosis and low risk of lymph node metastasis (LNM). However, risk factors of LNM and clinicopathological features for early gastric mixed signet ring cell carcinoma (mSRCC) remain poorly investigated. The aim of this study was to identify risk factors of LNM and compare clinicopathological characteristics and prognosis of early gastric pSRCC with mSRCC. Methods: This retrospective study was conducted at our center between 2005 and 2015 in 796 patients underwent radical gastrectomies combined with lymph node dissections, A total of 160 patients with early gastric SRCC underwent gastrectomies with lymph node dissections were reviewed, in which 79 cases were pSRCC and 81 cases were mSRCC. Risk factors of LNM and clinicopathologic features of these two groups were statistically compared, including age, gender, tumor location, gross pattern, size, invasion depth, lymphovascular invasion (LVI), helicobacter pylori (Hp) infection, atrophic gastritis, ulcer finding and LNM. Patients were follow-up for post-resection survival. The 5-year survival and disease-specific survival rate were estimated with the Kaplain-Meier method with a log-rank test and compared between the two groups. Results: Tumor size (P<0.05), invision depth (P<0.05) and LVI (P < 0.0001) were risk factors of LNM, LVI (P < 0.0001) was independent risk factor of LNM in 160 patients. Univariate analysis reviewed LVI (P < 0.0001) as the risk factor in the pSRCC group, and the risk factors of LNM in the mSRCC included LVI (P < 0.0001) and tumor size (P<0.05). Multivariable analysis revealed two independent risk factors in the mSRCC group: 1) tumor size (P < 0.05), and 2) LVI (P < 0.0001). The significant characteristics in two groups included the male gender (P < 0.0001), gross pattern (P < 0.05), LVI (P < 0.01), and Hp infection (P < 0.01). The difference of LNM rate between expanded indication and out of indication in 160 patients was significant (P=0.03). The overall 5-year survival rate for early gastric SRCC was 96.3%. There was no significant difference in the overall survival and disease-specific survival between the two groups. Conclusions: Although with similar post-resection survival, the independent risk factors of LNM in the early mSRCC group, compared to those in the early pSRCC group, included large tumor size and LVI. Early gastric mSRCC had more aggressive clinicopathological features than pSRCC.
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Affiliation(s)
- Qingqing Hu
- Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Raymond Dekusaah
- Department of Geriatric, Drum Tower Clinical College of Nanjing Medical University, Nanjing, China
| | - Shouli Cao
- Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Taohong Pang
- Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Yi Wang
- Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Bin Zhang
- Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Ying Lv
- Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Xiaoqi Zhang
- Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Tingsheng Ling
- Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Yuzheng Zhuge
- Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Lei Wang
- Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Xiaoping Zou
- Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Weijie Zhang
- Department of General Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Qin Huang
- Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
- VA Boston Healthcare System and Harvard Medical School, West Roxbury, MA 02132, USA
| | - Guifang Xu
- Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
- Department of Geriatric, Drum Tower Clinical College of Nanjing Medical University, Nanjing, China
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40
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Kook MC. Risk Factors for Lymph Node Metastasis in Undifferentiated-Type Gastric Carcinoma. Clin Endosc 2019; 52:15-20. [PMID: 30677790 PMCID: PMC6370926 DOI: 10.5946/ce.2018.193] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2018] [Accepted: 12/31/2018] [Indexed: 12/11/2022] Open
Abstract
Undifferentiated-type carcinoma has a high incidence of lymph node metastasis. The independent risk factors for lymph node metastasis in undifferentiated-type carcinoma are invasion depth, tumor size, lymphovascular invasion, and presence of ulcer. In the cases that meet the curative resection criteria, no lymph node metastasis was observed in the Japanese studies, but some metastases were observed in Korean studies. After performing curative endoscopic submucosal dissection, the survival rate is similar to that of gastrectomy. The discrepancy between endoscopy and pathology is high in undifferentiated-type carcinoma. The tumor size in endoscopy is a significant risk factor for non-curative resection, and when the tumor size is small, the non-curative resection rate is significantly reduced. Lymphovascular invasion can be assessed in pathologic examination and D2-40 stain is helpful. The presence of ulcer should be determined by pathology, but ulcer's omission in pathology report makes the analysis difficult. Undifferentiatedtype carcinomas with differentiated-type components show higher lymph node metastasis rate than that of pure undifferentiatedtype carcinomas. The lymph node metastasis rate of signet ring cell type is lower than that of other undifferentiated-type carcinomas and is similar to differentiated-type carcinomas. The application of these additional histologic findings may improve the indication of endoscopic submucosal dissection.
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41
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Kwak DS, Min YW, Lee JH, Kang SH, Jang SH, Lee H, Min BH, Kim JJ, Kim KM, Sohn TS, Kim S. Outcomes of Endoscopic Submucosal Dissection for Early Gastric Cancer with Undifferentiated-Type Histology: A Clinical Simulation Using a Non-Selected Surgical Cohort. Gut Liver 2018; 12:263-270. [PMID: 29271182 PMCID: PMC5945257 DOI: 10.5009/gnl17247] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2017] [Revised: 07/19/2017] [Accepted: 08/18/2017] [Indexed: 12/23/2022] Open
Abstract
Background/Aims Outcomes of endoscopic submucosal dissection (ESD) for undifferentiated-type early gastric cancer (EGC) need to be further evaluated. We aimed to simulate the outcomes of ESD for undifferentiated-type EGC from a surgical database. Methods Among 802 patients who underwent gastrectomy with endoscopic biopsy for poorly differentiated adenocarcinoma (PD-type) or signet ring cell carcinoma (SRC-type), ESD candidates meeting the expanded indication (n=280) were selected by reviewing the endoscopic images. According to the surgical pathologic results, the outcomes of the ESD simulation were evaluated. Results Among the candidates, 104 (37.1%) were PD-type and 176 (62.9%) were SRC-type. The curative resection (CR) rate was 42.1%. Among the patients with CR, three patients (2.5%) showed lymph node metastasis (LNM). Three EGCs with CR and LNM were mucosal cancers ≥1.0 cm in size. The CR rate was higher in the SRC-type than in the PD-type (48.3% vs 31.7%, respectively, p=0.007). In the SRC-type, the CR rate was increased, with a smaller size criterion for the ESD indication, but was similar between the 1.0 cm and 0.6 cm criteria (63.3% and 63.6%, respectively), whereas the CR rate was below 50% in all of the different tumor size criteria (2.0 to 0.6 cm) in the PD-type. Conclusions In undifferentiated-type EGC, ESD should be considered in selected patients with tumor sizes ＜1 cm and SRC histology.
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Affiliation(s)
- Dong Shin Kwak
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Yang Won Min
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jun Haeng Lee
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Soo Hoon Kang
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Seung Hyeon Jang
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Hyuk Lee
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Byung-Hoon Min
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jae J Kim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Kyoung-Mee Kim
- Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Tae Sung Sohn
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Sung Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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42
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Chen TH, Lin WR, Lee C, Chiu CT, Hsu JT, Yeh TS, Lin KH, Le PH, Yeh CT. Prognostic Stratification of Advanced Gastric Signet Ring Cell Carcinoma by Clinicopathological Factors and GALNT14 Genotype. J Cancer 2018; 9:3540-3547. [PMID: 30310511 PMCID: PMC6171017 DOI: 10.7150/jca.26293] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2018] [Accepted: 07/27/2018] [Indexed: 12/16/2022] Open
Abstract
Background: Gastric signet ring cell carcinoma (SRCC) is a histologic variant characterized by abundant intracytoplasmic mucin. Although it has been recognized that gastric adenocarcinoma harboring this feature has poorer prognosis, prognostic stratification within gastric SRCCs themselves has not been clearly defined. N-acetylgalactosaminyltransferase14 (GALNT14) genotype has been associated to poorer treatment outcome in mucinous type colorectal cancer. Here we incorporated clinicopathological factors and GALNT14 genotype to stratify prognosis of advanced gastric SRCC. Methods: Totally 347 gastric SRCC patients were retrospectively enrolled for GALNT14 genotyping. Clinicopathological factors were included for prognosis stratification. Results: Of the 347 patients, 341 underwent radical-intent gastrectomy and 6 received palliative gastrectomy. Kaplan-Meier analysis for overall survival indicated that Tumor-Node-Metastasis staging could only stratify the patients into three prognosis-distinguishable groups: group-1 (stage IA); group-2 (stage IB/IIA) and group-3 (the remaining Tumor-Node-Metastasis stages combined). Multivariate Cox-proportional hazard models for group-3 patients revealed GALNT14 "TT" genotype (P = 0.0482). Tumor size (P = 0.0009), node status (P <0.0001), metastasis status (P = 0.0096), and perineural invasion (P = 0.037) independently associated with unfavorable OS. Exploratory subgroup analysis showed that GALNT14"TT" genotype was associated with unfavorable OS in SRCCs with more aggressive phenotypes: node status >0 (P = 0.0013), lymphatic invasion (P = 0.021), vascular invasion (P = 0.0076) and perineural invasion (P = 0.0161). Accordingly, a scoring system was established capable of stratifying advanced gastric SRCC patients into three distinguishable prognostic subgroups. Conclusions: Gastric SRCC could be stratified into different prognostic subgroups by combining clinicopathological factors and GALNT14 genotype.
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Affiliation(s)
- Tsung-Hsing Chen
- Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan
- Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan, Taiwan
| | - Wey-Ran Lin
- Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan
- Liver Research Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan
| | - Chieh Lee
- Department of Industrial Engineering & Management, Yuan Ze University College of Engineering, Chung-Li City, Taiwan
| | - Cheng-Tang Chiu
- Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Jun-Te Hsu
- Department of Surgery, Chang Gung Memorial Hospital, Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Ta-Sen Yeh
- Department of Surgery, Chang Gung Memorial Hospital, Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Kwang-Huei Lin
- Liver Research Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan
- Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan
- Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology Taoyuan, Taiwan
| | - Puo-Hsien Le
- Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Chau-Ting Yeh
- Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan
- Liver Research Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan
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Su X, Xue Y, Wei J, Huo X, Gong Y, Zhang H, Han R, Chen Y, Chen H, Chen J. Establishment and Characterization of gc-006-03, a Novel Human Signet Ring Cell Gastric Cancer Cell Line Derived from Metastatic Ascites. J Cancer 2018; 9:3236-3246. [PMID: 30271482 PMCID: PMC6160672 DOI: 10.7150/jca.26051] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2018] [Accepted: 07/17/2018] [Indexed: 12/15/2022] Open
Abstract
Signet ring cell gastric cancer (SRCGC) is a special type of gastric cancer with rapid progression and poor prognosis. However, few available SRCGC cell lines from Chinese patients can be used for research, the molecular mechanism of its growth and metastasis is still incompletely understood. In this study, we established and characterized a novel SRCGC cell line, gc-006-03.The cells showed a tendency to pile up without contact inhibition. G-band karyotypes of gc-006-03 were revealed hypotriploid with a modal chromosome number of 51. Immunohistochemistry analysis showed that the cells were positive for CEA, CK7, CDX2 and Ki-67(45%), and negative for CK20, TTF1and Li-cadherin. Flow cytometry analysis showed that gc-006-3 had 25% of CD44+ cells. The cells possessed strong clonality and high plating efficiency, and the doubling time was 36h. The cells grew vigorously for more than 100 passages in serial culture. Meanwhile, the cells showed a high rate of tumor formation. Tumors were observed in all of the nude mice (5/5) given injections of the cells. The metastatic capability of the cell line was found in zebrafish injected the cells. The results of whole genome sequencing revealed the unique genomic characteristics of gc-006-03. In summary, this new stable cell line may be useful in basic and clinical research on gastric signet ring cell carcinoma.
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Affiliation(s)
- Xinyu Su
- Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.,Department of Radiation Oncology, the Affiliated Huai'an Hospital of Xuzhou Medical College, Huai'an, China
| | - Yiqi Xue
- Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Jingsun Wei
- Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Xinying Huo
- Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Yang Gong
- Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Honghong Zhang
- Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Rongbo Han
- Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Yuetong Chen
- Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Hong Chen
- Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Jinfei Chen
- Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
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Shu Y, Zhang W, Hou Q, Zhao L, Zhang S, Zhou J, Song X, Zhang Y, Jiang D, Chen X, Wang P, Xia X, Liao F, Yin D, Chen X, Zhou X, Zhang D, Yin S, Yang K, Liu J, Fu L, Zhang L, Wang Y, Zhang J, An Y, Cheng H, Zheng B, Sun H, Zhao Y, Wang Y, Xie D, Ouyang L, Wang P, Zhang W, Qiu M, Fu X, Dai L, He G, Yang H, Cheng W, Yang L, Liu B, Li W, Dong B, Zhou Z, Wei Y, Peng Y, Xu H, Hu J. Prognostic significance of frequent CLDN18-ARHGAP26/6 fusion in gastric signet-ring cell cancer. Nat Commun 2018; 9:2447. [PMID: 29961079 PMCID: PMC6026495 DOI: 10.1038/s41467-018-04907-0] [Citation(s) in RCA: 112] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2017] [Accepted: 05/31/2018] [Indexed: 02/05/2023] Open
Abstract
Signet-ring cell carcinoma (SRCC) has specific epidemiology and oncogenesis in gastric cancer, however, with no systematical investigation for prognostic genomic features. Here we report a systematic investigation conducted in 1868 Chinese gastric cancer patients indicating that signet-ring cells content was related to multiple clinical characteristics and treatment outcomes. We thus perform whole-genome sequencing on 32 pairs of SRC samples, and identify frequent CLDN18-ARHGAP26/6 fusion (25%). With 797 additional patients for validation, prevalence of CLDN18-ARHGAP26/6 fusion is noticed to be associated with signet-ring cell content, age at diagnosis, female/male ratio, and TNM stage. Importantly, patients with CLDN18-ARHGAP26/6 fusion have worse survival outcomes, and get no benefit from oxaliplatin/fluoropyrimidines-based chemotherapy, which is consistent with the fact of chemo-drug resistance acquired in CLDN18-ARHGAP26 introduced cell lines. Overall, this study provides insights into the clinical and genomic features of SRCC, and highlights the importance of frequent CLDN18-ARHGAP26/6 fusions in chemotherapy response for SRCC.
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Affiliation(s)
- Yang Shu
- Department of Gastrointestinal Surgery, Institute of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
- Precision Medicine Center, State Key Laboratory of Biotherapy and Precision Medicine, Key Laboratory of Sichuan Province, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Weihan Zhang
- Department of Gastrointestinal Surgery, Institute of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Qianqian Hou
- Precision Medicine Center, State Key Laboratory of Biotherapy and Precision Medicine, Key Laboratory of Sichuan Province, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Linyong Zhao
- Department of Gastrointestinal Surgery, Institute of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Shouyue Zhang
- Precision Medicine Center, State Key Laboratory of Biotherapy and Precision Medicine, Key Laboratory of Sichuan Province, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Jiankang Zhou
- State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Xiaohai Song
- Department of Gastrointestinal Surgery, Institute of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Yan Zhang
- Department of Thoracic Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, 610041, Chengdu, Sichuan, China
| | - Dan Jiang
- Department of Pathology, West China Hospital, Sichuan University, 610041, Chengdu, Sichuan, China
| | - Xinzu Chen
- Department of Gastrointestinal Surgery, Institute of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Peiqi Wang
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, 610041, Chengdu, China
| | - Xuyang Xia
- Precision Medicine Center, State Key Laboratory of Biotherapy and Precision Medicine, Key Laboratory of Sichuan Province, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Fei Liao
- Precision Medicine Center, State Key Laboratory of Biotherapy and Precision Medicine, Key Laboratory of Sichuan Province, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Dandan Yin
- Precision Medicine Center, State Key Laboratory of Biotherapy and Precision Medicine, Key Laboratory of Sichuan Province, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Xiaolong Chen
- Department of Gastrointestinal Surgery, Institute of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Xueyan Zhou
- Precision Medicine Center, State Key Laboratory of Biotherapy and Precision Medicine, Key Laboratory of Sichuan Province, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Duyu Zhang
- Precision Medicine Center, State Key Laboratory of Biotherapy and Precision Medicine, Key Laboratory of Sichuan Province, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Senlin Yin
- State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Kun Yang
- Department of Gastrointestinal Surgery, Institute of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Jianping Liu
- Department of Pathology, West China Hospital, Sichuan University, 610041, Chengdu, Sichuan, China
| | - Leilei Fu
- State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Lan Zhang
- State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Yuelan Wang
- Precision Medicine Center, State Key Laboratory of Biotherapy and Precision Medicine, Key Laboratory of Sichuan Province, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Junlong Zhang
- Department of Laboratory Medicine/Research Center of Clinical Laboratory Medicine, West China Hospital, Sichuan University, 610041, Chengdu, Sichuan, China
| | - Yunfei An
- Department of Laboratory Medicine/Research Center of Clinical Laboratory Medicine, West China Hospital, Sichuan University, 610041, Chengdu, Sichuan, China
| | - Hua Cheng
- WuxiNextCODE, 200131, Shanghai, China
| | - Bin Zheng
- WuxiNextCODE, 200131, Shanghai, China
| | | | - Yinglan Zhao
- State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Yongsheng Wang
- Department of Thoracic Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, 610041, Chengdu, Sichuan, China
| | - Dan Xie
- Precision Medicine Center, State Key Laboratory of Biotherapy and Precision Medicine, Key Laboratory of Sichuan Province, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
- State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Liang Ouyang
- State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Ping Wang
- Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA
| | - Wei Zhang
- Department of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Xiangya Hospital, Central South University, 410008, Changsha, China
| | - Meng Qiu
- Department of Abdominal Oncology, Cancer Center, West China Hospital, Sichuan University, 610041, Chengdu, Sichuan, China
| | - Xianghui Fu
- State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Lunzhi Dai
- State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Gu He
- State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Hanshuo Yang
- State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Wei Cheng
- State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Li Yang
- State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Bo Liu
- State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Weimin Li
- Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, 610041, Chengdu, Sichuan, China
| | - Biao Dong
- State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Zongguang Zhou
- Department of Gastrointestinal Surgery, Institute of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Yuquan Wei
- State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Yong Peng
- State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China.
| | - Heng Xu
- Precision Medicine Center, State Key Laboratory of Biotherapy and Precision Medicine, Key Laboratory of Sichuan Province, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China.
- State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China.
- Department of Laboratory Medicine/Research Center of Clinical Laboratory Medicine, West China Hospital, Sichuan University, 610041, Chengdu, Sichuan, China.
| | - Jiankun Hu
- Department of Gastrointestinal Surgery, Institute of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China.
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Incidence, Survival, and Predictors of Lymph Node Involvement in Early-Stage Gastric Signet Ring Cell Carcinoma in the US. J Gastrointest Surg 2018; 22:569-577. [PMID: 29313289 DOI: 10.1007/s11605-017-3500-4] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2017] [Accepted: 07/06/2017] [Indexed: 02/07/2023]
Abstract
INTRODUCTION The incidence, survival, and propensity for nodal metastasis in early-stage gastric signet ring cell carcinoma have not been defined in the United States. These data are critical determinants for treatment allocation. METHODS Cases of gastric signet ring cell carcinoma were extracted from the national SEER database for the years 2004-2013. Age-standardized incidence was derived. Survival was calculated using the Kaplan-Meier method. Univariate and multivariate analyses were performed to identify predictors of nodal metastasis. Exclusion criteria included neoadjuvant radiotherapy and lack of histologic or nodal data. RESULTS A total of 10,624 cases were initially identified. The analysis cohort included 506 cases with early T-stage N0M0 disease following exclusions. The incidence was 0.094 per 100,000 person-years. The 5-year survival rate was 82.8%. Tumor stage (p < 0.001) and size (p < 0.001) were independent predictors of nodal metastasis. The incidence of nodal involvement for T1a tumors <2 cm was 5.4% (p < 0.004). CONCLUSION The incidence of potentially resectable signet ring gastric carcinoma has not changed significantly over the past decade. While presenting with predominantly high-grade histology, early T-stage disease has a high survival rate. Small T1a tumors have low rates of nodal metastasis, suggesting that an endoscopic resection could be considered in this subset.
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Chen J, Cai R, Ren G, Zhao J, Li H, Guo C, He W, Wu X, Zhang W. Differences in clinicopathological characteristics and computed tomography findings between signet ring cell carcinoma and nonsignet ring cell carcinoma in early and advanced gastric cancer. Cancer Med 2018. [PMID: 29533002 PMCID: PMC5911613 DOI: 10.1002/cam4.1417] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Signet ring cell carcinoma (SRC) of the stomach is a histological type based on microscopic characteristics. SRC's clinicopathological characteristics and prognosis are still controversial. Our study is to describe the clinicopathological features and multidetector computed tomography (MDCT) findings of patients with SRC of the stomach in comparison with nonsignet ring cell adenocarcinoma (NSRC). We retrospectively analyzed data from 241 patients who had undergone curative gastrectomy, including 62 SRC and 179 NSRC. Clinicopathological outcomes and MDCT findings were evaluated, and we investigated whether these variables were correlated with histopathological type. In early gastric carcinoma, patients with SRC were younger (50.2 vs. 60.2 years; P = 0.000) and more likely to be observed in the middle and lower third stomach (P = 0.010). Early SRC had a tendency to be confined to the mucosa (82.1%). There were significant differences in degree of enhancement between early SRC and NSRC on MDCT imaging (P < 0.001). In advanced gastric carcinoma, SRC was more likely to be stage T3‐4 (100%). SRC patients had thicker tumors (P = 0.001) and a higher frequency of diffusely infiltrative gross appearance (P < 0.001). SRC was more likely to have high‐degree contrast enhancement than were NSRC (P = 0.001). The maximal diameter of SRC tumor on MDCT imaging correlated with lymph node metastasis (sensitivity 93.9%, specificity 74.1%) and serosal invasion (sensitivity 89.5%, specificity 78.0%) of SRC. In conclusion, SRC differs significantly from NSRC in clinicopathological features at presentation. MDCT could help differentiate advanced gastric SRC from NSRC based on the thickened stomach wall, high‐degree contrast enhancement, and a higher frequency of diffusely infiltrative gross appearance, particularly in combination.
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Affiliation(s)
- Jian Chen
- Department of Radiology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200092, China
| | - Rong Cai
- Department of Radiotherapy, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China
| | - Gang Ren
- Department of Radiology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200092, China
| | - Jianxi Zhao
- Department of Radiology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200092, China
| | - Huali Li
- Department of Radiology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200092, China
| | - Chen Guo
- Department of Radiology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200092, China
| | - Wenguang He
- Department of Radiology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200092, China
| | - Xiangru Wu
- Department of Pathology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200092, China
| | - Wenjie Zhang
- Department of Surgery, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200092, China
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Abstract
This research aims to explore the potential risk factors of lymph node metastasis (LNM) for early gastric cancers in young patients.We retrospectively collected data from 4287 patients who underwent gastrectomy from January 2005 to December 2015 at Linyi People's Hospital. Of these, we enrolled 397 eligible consecutive patients who had early gastric cancer, then divided them into 2 groups according to age (≤40 years and >40 years). The association between the clinicopathological factors and LNM was analyzed by univariate and multivariate analysis.Compared to older patients (>40 years), younger patients (≤40 years) with early gastric cancer had more diffuse and mixed types (51.1% and 37.8% vs 40% and 8.3%, respectively), less proximal gastric cancer (0% vs 33.8%, P < .01) and higher LNM (33.3% vs 13%, P < .01). Univariate analysis showed tumor invasion depth (P < .01), lymphovascular invasion (P < .01), and E-cadherin expression (P = .024) were associated with LNM in the younger cohort. Multivariate analysis revealed that lymphovascular invasion (OR = 17.740, 95% CI: 1.458-215.843) was an independent risk factor for LNM (P = .024). Further analysis showed 3 patients who were within expanded endoscopic resection indications were positive for LNM.Given the high risk of lymph node involvement in young patients with early gastric cancer, both endoscopic and surgical resection procedures should be performed with caution, and active postoperative surveillance is warranted.
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Affiliation(s)
- Tao Ji
- Department of Gastroenterology, Linyi People's Hospital, Linyi, Shandong Province
| | - Fan Zhou
- Department of Gastroenterology, Drum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing, Jiangsu Province, China
| | - John Wang
- Department of Gastroenterology and Hepatology, Royal Prince Alfred Hospital, Sydney, NSW, Australia
| | - Li Zi
- Department of General Surgery, Linyi People's Hospital, Linyi, Shandong Province, China
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Zhao X, Cai A, Xi H, Song Y, Wang Y, Li H, Li P, Chen L. Predictive factors for lymph node metastasis in early gastric cancer with signet ring cell histology: a meta-analysis. ANZ J Surg 2017; 87:981-986. [PMID: 28681963 DOI: 10.1111/ans.14089] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2017] [Revised: 05/02/2017] [Accepted: 05/03/2017] [Indexed: 12/25/2022]
Abstract
BACKGROUND Less invasive surgery is widely used in the treatment of early gastric cancer; however, no definite guidelines exist regarding indications for less invasive surgery to treat early gastric cancer with signet ring cell histology. The aim of this study was to identify risk factors for lymph node metastasis (LNM) in early signet ring cell carcinoma (SRC). An extensive search of PubMed, Embase and the Cochrane library was performed for pertinent articles involving early SRC and LNM. METHODS Eligible data (gender, depth of invasion, lymphovascular invasion, size, ulceration, macroscopic type and location) were extracted from the included studies and systematically reviewed via a meta-analysis. Review Manager version 5.3 was used to perform the data processing. The Newcastle-Ottawa Scale was utilized to evaluate the quality of the included articles. RESULTS Fourteen studies were included in the final analysis. After meta-analysis, female gender, submucosal invasion, lymphovascular invasion and size >20 mm were associated with LNM in early SRC. CONCLUSION Four variables were identified as risk factors for LNM in early SRC. The significance of the results of the present study should be further confirmed in more early SRC patients for future clinical use.
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Affiliation(s)
- Xudong Zhao
- Department of General Surgery, Chinese People's Liberation Army General Hospital, Beijing, China
| | - Aizhen Cai
- Department of General Surgery, Chinese People's Liberation Army General Hospital, Beijing, China
| | - Hongqing Xi
- Department of General Surgery, Chinese People's Liberation Army General Hospital, Beijing, China
| | - Yanjing Song
- Department of General Surgery, Chinese People's Liberation Army General Hospital, Beijing, China
| | - Yi Wang
- Department of General Surgery, Chinese People's Liberation Army General Hospital, Beijing, China
| | - Hua Li
- Department of General Surgery, Chinese People's Liberation Army General Hospital, Beijing, China.,Department of Surgical Oncology, Affiliated Xing Tai People Hospital of Hebei Medical University, Xingtai, Hebei, China
| | - Peiyu Li
- Department of General Surgery, Chinese People's Liberation Army General Hospital, Beijing, China
| | - Lin Chen
- Department of General Surgery, Chinese People's Liberation Army General Hospital, Beijing, China
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A Risk-prediction Model Based on Lymph-node Metastasis for Incorporation Into a Treatment Algorithm for Signet Ring Cell-type Intramucosal Gastric Cancer. Ann Surg 2017; 264:1038-1043. [PMID: 27828821 DOI: 10.1097/sla.0000000000001602] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
OBJECTIVE The aim of the study was to develop a reliable and easy-to-use risk-scoring system (RSS) to predict lymph-node metastasis (LNM) and determine the feasibility of endoscopic submucosal dissection for mucosa-confined signet ring cell carcinomas (SRCs). BACKGROUND Fewer LNM and better survival rates have been reported for early gastric SRCs compared with other undifferentiated early gastric cancers (EGCs). METHODS Data from 1544 patients with mucosa-confined SRCs were reviewed. Stepwise logistic regression analysis determined the independent predictors of LNM. Risk scores were based on the final predictive factors for LNM, and performance was internally validated using a split-sample approach. External validation was also performed in an independent dataset (n = 208) to assess the discriminatory power of the RSS. RESULTS The overall LNM incidence was 3.8% (57/1544). Three risk factors (tumor size ≥1.7 cm, tumors of elevated type, and lymphatic-vascular involvement) were significantly associated with LNM. These factors were incorporated into the RSS, and were assigned scores ranging from 0 to 4. The area under the receiver-operating characteristic curve for predicting LNM after internal and external validation was 0.68 (95% confidence interval, 0.0793-0.2865) and 0.686 (95% confidence interval, 0.618-0.748), respectively. A score of 2 points was the optimal cut-off value for LNM prediction, and the overall diagnostic accuracy was 96%. LNM were found in 2.9% and 23.8% of the low and high-risk groups of the RSS, respectively. CONCLUSIONS A RSS may help to predict LNM and evaluate endoscopic submucosal dissection feasibility in patients with intramucosal SRC.
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Zhao X, Cai A, Xi H, Chen L, Peng Z, Li P, Liu N, Cui J, Li H. Predictive Factors for Lymph Node Metastasis in Undifferentiated Early Gastric Cancer: a Systematic Review and Meta-analysis. J Gastrointest Surg 2017; 21:700-711. [PMID: 28120275 DOI: 10.1007/s11605-017-3364-7] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2016] [Accepted: 01/04/2017] [Indexed: 01/31/2023]
Abstract
OBJECTIVES Less invasive surgery is gaining popularity for the treatment of early gastric cancer (EGC), but there are no definitive guidelines for the use of less invasive surgery for the treatment of undifferentiated EGC. The aims of this meta-analysis were to identify potential predictive factors for lymph node metastasis (LNM) in undifferentiated EGC and to guide the personalized therapeutic modality for patients with undifferentiated EGC. METHODS An extensive search of the PubMed, Embase, and Cochrane Library databases was performed to identify relevant articles involving undifferentiated EGC and LNM. Eligible data were systematically reviewed through a meta-analysis using Review Manager 5.3. RESULTS In total, 23 studies were included in this analysis. The meta-analysis found that the variables sex (female), age (greater than 60 years), tumor size (greater than 20 mm), depth of invasion (submucosal invasion), presence of lymphovascular involvement, presence of ulcer findings, histology type (non-signet ring carcinoma), and tumor location (not in the middle part of the stomach) were significantly associated with LNM. CONCLUSIONS Eight variables were identified as predictive factors for LNM in undifferentiated EGC. The significance of these variables should be further confirmed during the process of LNM in undifferentiated EGC patients for future clinical application.
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Affiliation(s)
- Xudong Zhao
- Department of General Surgery, Chinese People's Liberation Army General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100853, China
| | - Aizhen Cai
- Department of General Surgery, Chinese People's Liberation Army General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100853, China
| | - Hongqing Xi
- Department of General Surgery, Chinese People's Liberation Army General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100853, China
| | - Lin Chen
- Department of General Surgery, Chinese People's Liberation Army General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100853, China.
| | - Zheng Peng
- Department of General Surgery, Chinese People's Liberation Army General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100853, China.
| | - Peiyu Li
- Department of General Surgery, Chinese People's Liberation Army General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100853, China
| | - Na Liu
- Department of General Surgery, Chinese People's Liberation Army General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100853, China
| | - Jianxin Cui
- Department of General Surgery, Chinese People's Liberation Army General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100853, China
| | - Hua Li
- Department of General Surgery, Chinese People's Liberation Army General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100853, China.,Department of Surgical Oncology, Affiliated Xing Tai People Hospital of Hebei Medial University, Xingtai, 054001, Hebei Province, China
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