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Luo D, Wang H, Liu J, Chen X, Xu Y, Liang Y, Wang G, Zheng J, Chen Y, Wang X, Yu Z, Lian L. Combined MDM2 and G2/M checkpoint inhibition induces synergistic antitumor response in gastric signet-ring cell carcinoma. Cancer Lett 2025; 613:217500. [PMID: 39894196 DOI: 10.1016/j.canlet.2025.217500] [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: 05/19/2024] [Revised: 01/17/2025] [Accepted: 01/22/2025] [Indexed: 02/04/2025]
Abstract
Signet ring cell carcinoma (SRCC) poses a considerable challenge in terms of treatment, given its refractory nature and poor outcomes. Unlike other cancers, SRCC exhibits significant MDM2 copy number gains, with elevated MDM2 expression linked to poor prognosis. MDM2 inhibition induces a morphological transition in SRCC cells by suppressing E-cadherin degradation, which may render these cells vulnerable to a second drug. Using a high-throughput drug screen, our study demonstrated that the combination of MDM2 inhibitors with G2/M checkpoint inhibitors, including WEE1 or CHK1 inhibitors, can elicit a synergistic antitumor response in SRCC cells by inducing DNA damage. Furthermore, pharmacological inhibition of MDM2, WEE1, or CHK1 significantly impeded tumor growth in in vivo mouse models and organoids of SRCC. Collectively, our findings indicate that MDM2 inhibition-induced morphological changes may enhance the efficacy of G2/M checkpoint inhibitors, presenting a promising combined treatment for SRCC.
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Affiliation(s)
- Dandong Luo
- Department of General Surgery (Gastric Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, China; Department of Pathology, The First People's Hospital of Kashi Prefecture, Kashi, China
| | - Huashe Wang
- Department of General Surgery (Gastric Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, China
| | - Jun Liu
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, China; Department of Clinical Laboratory, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xiaochuan Chen
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, China; Department of Obstetrics and Gynecology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yucheng Xu
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, China
| | - Yufan Liang
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, China
| | - Guannan Wang
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, China; Department of Pathology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Jiabo Zheng
- Department of General Surgery (Gastric Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, China
| | - Yonghe Chen
- Department of General Surgery (Gastric Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, China
| | - Xinyou Wang
- Department of General Surgery (Gastric Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, China.
| | - Zhaoliang Yu
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, China; Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
| | - Lei Lian
- Department of General Surgery (Gastric Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, China.
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Tanaka R, Endo S, Yamaguchi T, Miyagaki H, Kawada J, Omori T, Takahashi N, Masuzawa T, Furukawa H, Sato Y, Takeno A, Shinno N, Kawabata R, Katsuyama S, Higashi S, Kurokawa Y, Tsujinaka T, Shimokawa T, Satoh T. Neoadjuvant docetaxel, oxaliplatin, and S-1 therapy for patients with large type 3 or type 4 gastric cancer: short-term outcomes of a multicenter, phase II study (OGSG1902). Gastric Cancer 2025:10.1007/s10120-025-01608-8. [PMID: 40159580 DOI: 10.1007/s10120-025-01608-8] [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] [Received: 01/26/2025] [Accepted: 03/17/2025] [Indexed: 04/02/2025]
Abstract
BACKGROUND Large type 3 (≥ 8 cm) and type 4 gastric cancers (GCs) have poor prognoses and necessitate multidisciplinary treatment. A multi-institutional phase II study (OGSG1902) was conducted to assess the efficacy and safety of neoadjuvant chemotherapy (NAC) with docetaxel, oxaliplatin, and S-1 (DOS) in these patients. METHODS Patients with large type 3 or type 4 GC without distant metastasis, except for positive peritoneal cytology (CY), were enrolled. Patients received three courses of neoadjuvant DOS therapy (docetaxel 40 mg/m2 and oxaliplatin 100 mg/m2 on day 1 via intravenous infusion, and S-1 80 mg/m2 orally for 14 days, repeated every 3 weeks) followed by gastrectomy. After R0 resection, adjuvant docetaxel/S-1 therapy was administered for 1 year. RESULTS From October 2019 to February 2022, 48 patients were enrolled. NAC was completed in 91.7% of patients. The R0 resection rate was 89.6%. The pathological response rate (Grade 1b-3) was 66.7%. Among patients with measurable lesions, the response rate was 50.0%. The CY-negative conversion rate was 80.0%, and the protocol completion rate was 45.8%. Grade 3 or 4 adverse events during NAC, including neutropenia and appetite loss, occurred in 37.5% of patients. Major postoperative complications (Clavien-Dindo Grade IIIa or higher) were observed in 2.1% of patients. CONCLUSIONS NAC with DOS for large type 3 or type 4 GC followed by gastrectomy demonstrated promising efficacy, high pathological response rates, and an acceptable toxicity profile. Further evaluation of long-term survival outcomes is ongoing.
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Affiliation(s)
- Ryo Tanaka
- Department of General and Gastroenterological Surgery, Osaka Medical and Pharmaceutical University, Takatsuki, Japan
| | - Shunji Endo
- Department of Digestive Surgery, Kawasaki Medical School, Kurashiki, Japan
| | - Toshifumi Yamaguchi
- Cancer Chemotherapy Center, Osaka Medical and Pharmaceutical University, 2-7 Daigaku-Machi, , Takatsuki City, Osaka, Japan.
| | | | - Junji Kawada
- Department of Surgery, Yao Municipal Hospital, Yao, Japan
| | - Takeshi Omori
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Naoki Takahashi
- Department of Gastroenterology, Saitama Prefectural Cancer Center, Saitama, Japan
| | - Toru Masuzawa
- Department of Surgery, Kansai Rosai Hospital, Amagasaki, Japan
| | - Haruna Furukawa
- Department of Gastroenterological Surgery, Rinku General Medical Center, Izumisano, Japan
| | - Yuya Sato
- Department of Gastrointestinal Surgery, Institute of Science Tokyo Hospital, Tokyo, Japan
| | - Atsushi Takeno
- Department of Surgery, NHO Osaka National Hospital, Osaka, Japan
| | - Naoki Shinno
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan
| | | | | | - Shigeyoshi Higashi
- Department of Gastroenterological Surgery, Rinku General Medical Center, Izumisano, Japan
| | - Yukinori Kurokawa
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Japan
| | | | - Toshio Shimokawa
- Clinical Study Support Center, Wakayama Medical University, Wakayama, Japan
| | - Taroh Satoh
- Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of Medicine, Suita, Japan
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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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Kabatnik S, Zheng X, Pappas G, Steigerwald S, Padula MP, Mann M. Deep visual proteomics reveals DNA replication stress as a hallmark of signet ring cell carcinoma. NPJ Precis Oncol 2025; 9:37. [PMID: 39910169 PMCID: PMC11799539 DOI: 10.1038/s41698-025-00819-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Accepted: 01/17/2025] [Indexed: 02/07/2025] Open
Abstract
Signet Ring Cell Carcinoma (SRCC) is a rare and highly malignant form of adenocarcinoma with increasing incidence and poor prognosis due to late diagnosis and limited treatment options. We employed Deep Visual Proteomics (DVP), which combines AI-directed cell segmentation and classification with laser microdissection and ultra-high sensitivity mass spectrometry, for cell-type-specific proteomic analysis of SRCC across the bladder, prostate, seminal vesicle, and a lymph node of a single patient. DVP identified significant alterations in DNA damage response (DDR) proteins, particularly within the ATR and mismatch repair (MMR) pathways, indicating replication stress as a crucial factor in SRCC mutagenicity. Additionally, we observed substantial enrichment of immune-related proteins, reflecting high levels of cytotoxic T lymphocyte infiltration and elevated PD-1 expression. These findings suggest that pembrolizumab immunotherapy may be more effective than conventional chemotherapy for this patient. Our results provide novel insights into the proteomic landscape of SRCC, identify potential targets, and open up for personalized therapeutic strategies in managing SRCC.
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Affiliation(s)
- Sonja Kabatnik
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark
| | - Xiang Zheng
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark
- Department of Biomedicine, Aarhus University, Aarhus, Denmark
| | - Georgios Pappas
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark
| | - Sophia Steigerwald
- Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany
| | - Matthew P Padula
- School of Life Sciences and Proteomics Core Facility, Faculty of Science, University of Technology Sydney, Ultimo, Australia.
| | - Matthias Mann
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark.
- Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany.
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Sreeram A, Stroobant EE, Laszkowska M, Guilford P, Shimada S, Nishimura M, Shah S, Vardhana S, Tang LH, Strong VE. Disappearing Signet Ring Cell Adenocarcinoma in Gastric Cancer Patients. Ann Surg Oncol 2024; 31:9030-9038. [PMID: 39343820 DOI: 10.1245/s10434-024-16117-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Accepted: 08/16/2024] [Indexed: 10/01/2024]
Abstract
BACKGROUND The incidence of diffuse-type gastric cancer is increasing steadily in the United States, Europe, and Asia. This subtype is known for aggressive clinical characteristics and transmural invasion. However, T1a diffuse-type cancers have been observed to have a better 5-year, disease-specific mortality than stage-matched intestinal tumors, supporting a clinical difference in these early-stage cancers. METHODS Data on all living patients with T1a gastric adenocarcinoma with a finding of signet ring cell morphology on pathology and ≥1 year of follow-up from 2013 to 2023 at Memorial Sloan Kettering Cancer Center (MSK) was collected from a prospectively maintained database. Patients with known CDH1 or CTNNA1 mutations were excluded. RESULTS In 7 of 30 patients, sporadic pathologically confirmed T1a signet ring cell (diffuse) cancer identified on initial biopsy was no longer detectable upon subsequent biopsy or resection with mean follow-up of 50 months. CONCLUSIONS These cases allude to the distinct pathways of carcinogenesis in T1a signet ring cell cancers. Potential factors that may underlie the spontaneous regression of these T1a cancers include complete removal at initial biopsy, immune clearance, and lack of survival advantage conferred by signet ring cell genetic alterations in these cases. Given their more indolent behavior at an earlier stage, we suggest that these lesions can be closely followed by endoscopy in select circumstances with thorough disease assessment and an experienced care team.
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Affiliation(s)
- Aravind Sreeram
- Department of Surgery, Gastric and Mixed Tumor Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Emily E Stroobant
- Department of Surgery, Gastric and Mixed Tumor Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Monika Laszkowska
- Department of Medicine, Gastroenterology, Hepatology, and Nutrition Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Parry Guilford
- Department of Biochemistry, Cancer Genetics Laboratory, Centre for Translational Cancer Research (Te Aho Matatu), University of Otago, Dunedin, New Zealand
| | - Shoji Shimada
- Department of Surgery, Gastric and Mixed Tumor Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Makoto Nishimura
- Department of Medicine, Gastroenterology, Hepatology, and Nutrition Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Sohrab Shah
- Computational Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Santosha Vardhana
- Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Laura H Tang
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Vivian E Strong
- Department of Surgery, Gastric and Mixed Tumor Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
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Shi H, Yang H, Yan S, Zhang Q, Wang X. Development and validation of nomograms based on the SEER database for the risk factors and prognosis of distant metastasis in gastric signet ring cell carcinoma. Medicine (Baltimore) 2024; 103:e40382. [PMID: 39496020 PMCID: PMC11537633 DOI: 10.1097/md.0000000000040382] [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: 11/10/2023] [Accepted: 10/16/2024] [Indexed: 11/06/2024] Open
Abstract
Poor prognosis in patients with distant metastasis of gastric signet ring cell carcinoma (GSRC), and there are few studies on the development and validation of the diagnosis and prognosis of distant metastasis of GSRC. The Surveillance, Epidemiology, and End Results database was used to identify patients with GSRC from 2004 to 2019. Univariate and multivariate logistic regression analysis were used to identify independent risk factors for distant metastasis of GSRC, while univariate and multivariate Cox proportional hazard regression analysis were used to determine independent prognostic factors for patients with distant metastasis of GSRC. Two nomograms were established, and model performance was evaluated using receiver operating characteristic curves, calibration plots, and decision curve analysis. A total of 9703 cases with GSRC were enrolled, among which 2307 cases (23.78%) were diagnosed with distant metastasis at the time of diagnosis. Independent risk factors for distant metastasis included age, race, and T stage. Independent prognostic factors included T stage, chemotherapy, and surgery. The receiver operating characteristic curve, calibration curve, decision curve analysis curve, and Kaplan-Meier survival curve of the training set and validation set confirmed that the 2 nomograms could accurately predict the occurrence and prognosis of distant metastasis in GSRC. Two nomograms can serve as effective prediction tools for predicting distant metastasis in GSRC patients and the prognosis of patients with distant metastasis. They have a certain clinical reference value.
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Affiliation(s)
- Haomin Shi
- Department of Public Health, Qinghai University School of Medicine, Xining, China
- Qinghai Provincial People’s Hospital, Xining, China
| | - Huilian Yang
- Department of Public Health, Qinghai University School of Medicine, Xining, China
| | - Su Yan
- Affiliated Hospital of Qinghai University, Xining, China
| | - Qi Zhang
- Department of Public Health, Qinghai University School of Medicine, Xining, China
| | - Xingbin Wang
- Department of Public Health, Qinghai University School of Medicine, Xining, China
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Yu ZH, Zhang LM, Dai ZQ, Zhang MN, Zheng SM. Epidemiology and prognostic nomogram for locally advanced gastric signet ring cell carcinoma: A population-based study. World J Gastrointest Oncol 2024; 16:2610-2630. [PMID: 38994168 PMCID: PMC11236255 DOI: 10.4251/wjgo.v16.i6.2610] [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: 01/05/2024] [Revised: 04/06/2024] [Accepted: 04/12/2024] [Indexed: 06/14/2024] Open
Abstract
BACKGROUND Gastric signet ring cell carcinoma (GSRC) represents a specific subtype of gastric cancer renowned for its contentious epidemiological features, treatment principles, and prognostic factors. AIM To investigate the epidemiology of GSRC and establish an improved model for predicting the prognosis of patients with locally advanced GSRC (LAGSRC) after surgery. METHODS The annual rates of GSRC incidence and mortality, covering the years 1975 to 2019, were extracted from the Surveillance, Epidemiology, and End Results (SEER) database to explore the temporal trends in both disease incidence and mortality rates using Joinpoint software. The clinical data of 3793 postoperative LAGSRC patients were collected from the SEER database for the analysis of survival rates. The Cox regression model was used to explore the independent prognostic factors for overall survival (OS). The risk factors extracted were used to establish a prognostic nomogram. RESULTS The overall incidence of GSRC increased dramatically between 1975 and 1998, followed by a significant downward trend in incidence after 1998. In recent years, there has been a similarly optimistic trend in GSRC mortality rates. The trend in GSRC showed discrepancies based on age and sex. Receiver operating characteristic curves, calibration curves, and decision curve analysis for 1-year, 3-year, and 5-year OS demonstrated the high discriminative ability and clinical utility of this nomogram. The area under the curve indicated that the performance of the new model outperformed that of the pathological staging system. CONCLUSION The model we established can aid clinicians in the early prognostication of LAGSRC patients, resulting in improved clinical outcomes by modifying management strategies and patient health care.
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Affiliation(s)
- Ze-Hao Yu
- Health Science Center, The First Affiliated Hospital of Ningbo University, Ningbo 315000, Zhejiang Province, China
- Health Science Center, Ningbo University, Ningbo 315211, Zhejiang Province, China
| | - Lei-Ming Zhang
- Health Science Center, Ningbo University, Ningbo 315211, Zhejiang Province, China
| | - Zhi-Qi Dai
- Health Science Center, The First Affiliated Hospital of Ningbo University, Ningbo 315000, Zhejiang Province, China
- Health Science Center, Ningbo University, Ningbo 315211, Zhejiang Province, China
| | - Meng-Na Zhang
- Health Science Center, The First Affiliated Hospital of Ningbo University, Ningbo 315000, Zhejiang Province, China
- College of Medicine, The First Affiliated Hospital of Zhejiang University, Hangzhou 310058, Zhejiang Province, China
| | - Si-Ming Zheng
- Health Science Center, The First Affiliated Hospital of Ningbo University, Ningbo 315000, Zhejiang Province, China
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Yu ZH, Zhang LM, Dai ZQ, Zhang MN, Zheng SM. Epidemiology and prognostic nomogram for locally advanced gastric signet ring cell carcinoma: A population-based study. World J Gastrointest Oncol 2024; 16:2598-2618. [DOI: 10.4251/wjgo.v16.i6.2598] [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: 01/05/2024] [Revised: 04/06/2024] [Accepted: 04/12/2024] [Indexed: 06/13/2024] Open
Abstract
BACKGROUND Gastric signet ring cell carcinoma (GSRC) represents a specific subtype of gastric cancer renowned for its contentious epidemiological features, treatment principles, and prognostic factors.
AIM To investigate the epidemiology of GSRC and establish an improved model for predicting the prognosis of patients with locally advanced GSRC (LAGSRC) after surgery.
METHODS The annual rates of GSRC incidence and mortality, covering the years 1975 to 2019, were extracted from the Surveillance, Epidemiology, and End Results (SEER) database to explore the temporal trends in both disease incidence and mortality rates using Joinpoint software. The clinical data of 3793 postoperative LAGSRC patients were collected from the SEER database for the analysis of survival rates. The Cox regression model was used to explore the independent prognostic factors for overall survival (OS). The risk factors extracted were used to establish a prognostic nomogram.
RESULTS The overall incidence of GSRC increased dramatically between 1975 and 1998, followed by a significant downward trend in incidence after 1998. In recent years, there has been a similarly optimistic trend in GSRC mortality rates. The trend in GSRC showed discrepancies based on age and sex. Receiver operating characteristic curves, calibration curves, and decision curve analysis for 1-year, 3-year, and 5-year OS demonstrated the high discriminative ability and clinical utility of this nomogram. The area under the curve indicated that the performance of the new model outperformed that of the pathological staging system.
CONCLUSION The model we established can aid clinicians in the early prognostication of LAGSRC patients, resulting in improved clinical outcomes by modifying management strategies and patient health care.
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Affiliation(s)
- Ze-Hao Yu
- Health Science Center, The First Affiliated Hospital of Ningbo University, Ningbo 315000, Zhejiang Province, China
- Health Science Center, Ningbo University, Ningbo 315211, Zhejiang Province, China
| | - Lei-Ming Zhang
- Health Science Center, Ningbo University, Ningbo 315211, Zhejiang Province, China
| | - Zhi-Qi Dai
- Health Science Center, The First Affiliated Hospital of Ningbo University, Ningbo 315000, Zhejiang Province, China
- Health Science Center, Ningbo University, Ningbo 315211, Zhejiang Province, China
| | - Meng-Na Zhang
- Health Science Center, The First Affiliated Hospital of Ningbo University, Ningbo 315000, Zhejiang Province, China
- College of Medicine, The First Affiliated Hospital of Zhejiang University, Hangzhou 310058, Zhejiang Province, China
| | - Si-Ming Zheng
- Health Science Center, The First Affiliated Hospital of Ningbo University, Ningbo 315000, Zhejiang Province, China
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Ji J, Zhang X, Yuan S, Liu H, Yang L. Survival impact of gastrectomy and chemotherapy on gastric signet ring-cell carcinoma with different metastatic lesions: A population-based study. Asian J Surg 2024; 47:1769-1775. [PMID: 38302357 DOI: 10.1016/j.asjsur.2024.01.129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Revised: 11/26/2022] [Accepted: 01/19/2024] [Indexed: 02/03/2024] Open
Abstract
BACKGROUND A comprehensive understanding of gastric signet ring cell carcinoma (SRCC) is limited. The aim of our study was to analyze metastatic patterns of gastric SRCC and evaluate impacts of gastrectomy and chemotherapy for metastatic gastric SRCC. METHODS We obtained data of gastric cancer patients between 2010 and 2017 in the Surveillance, Epidemiology, and End Results database. Chi-square tests were used to compare data significance. Kaplan-Meier, Cox proportional hazards regression and Fine-Gray competing risk analysis were used to analyze the difference in the overall survival (OS) and cancer-specific survival (CSS). Propensity-score matching was used to adjust numerical difference. RESULTS Among 36,459 eligible gastric cancer patients, 6264 (17.2 %) were SRCC patients. Bone metastasis was more common in SRCC patients than in non-SRCC patients. The multivariate analysis showed that chemotherapy (HR = 0.30, 95 %CI = 0.27-0.33, p < 0.01) and gastrectomy (HR = 0.51, 95 %CI = 0.45-0.59, p < 0.01) were protective prognostic factors in certain stage Ⅳ SRCC patients. For the effect of gastrectomy, survival benefits could be found in patients with liver metastasis. The gastrectomy was not associated with improved OS in patients with lung or multiple metastases. In subgroup analysis, SRCC patients with metastasis who received gastrectomy and chemotherapy (HR = 0.17, p < 0.01; HR = 0.03, p < 0.01) had a better OS and CSS than those who had chemotherapy only (HR = 0.30, p < 0.01; HR = 0.18, p < 0.01). CONCLUSION Our study analyzed the unique metastatic patterns of gastric SRCC and recommended chemotherapy as the first choice in metastatic SRCC. For patients with liver metastasis, gastrectomy plus chemotherapy can be considered.
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Affiliation(s)
- Jiali Ji
- Department of Medical Oncology, Affiliate Tumor Hospital of Nantong University, Nantong, China.
| | - Xunlei Zhang
- Department of Medical Oncology, Affiliate Tumor Hospital of Nantong University, Nantong, China.
| | - Shushu Yuan
- Department of Medical Oncology, Affiliate Tumor Hospital of Nantong University, Nantong, China.
| | - Hong Liu
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Medical Oncology, Sun Yat-sen University Cancer Center, China.
| | - Lei Yang
- Department of Medical Oncology, Affiliate Tumor Hospital of Nantong University, Nantong, China.
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10
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Boubaddi M, Teixeira Farinha H, Lambert C, Pereira B, Piessen G, Gualtierotti M, Voron T, Mantziari S, Pezet D, Gronnier C. Total Versus Subtotal Gastrectomy for Distal Gastric Poorly Cohesive Carcinoma. Ann Surg Oncol 2024; 31:744-752. [PMID: 37971616 DOI: 10.1245/s10434-023-14496-y] [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: 07/13/2023] [Accepted: 10/10/2023] [Indexed: 11/19/2023]
Abstract
BACKGROUND Gastric poorly cohesive carcinoma (PCC) in advanced stages has a poor prognosis. Total gastrectomy (TG) remains the common treatment for distal gastric PCC, but subtotal gastrectomy (SG) may improve quality of life without compromising outcomes. Currently, no clear recommendation on the best surgical strategy for distal PCC is available. This study aimed to compare overall survival (OS) and disease-free survival (DFS) at 5 years for patients with antropyloric PCC treated by total versus subtotal gastrectomy. METHODS A large retrospective European multicenter cohort study analyzed 2131 patients treated for gastric cancer between 2007 and 2017 by members of the French Association of Surgery (AFC). The study compared a group of patients who underwent TG with a group who underwent SG for antropyloric PCC. The primary outcomes were 5 year OS and DFS. RESULTS The study enrolled 269 patients: 140 (52.0%) in the TG group and 129 (48.0%) in the SG group. The baseline characteristics and pTNM stage were similar between the two groups. According to Dindo-Claven classification, the patients treated with TG had more postoperative complications than the patients treated with SG (p < 0.001): grades I to IIIa (77.1% vs 59.5%) and grades IIIb to IVb (14.4% vs 9.0%). No difference in 5-year OS was observed between TG (53.8%; 95 % confidence interval [CI], 43.2-63.3%) and SG (53.0%; 95% CI, 41.4-63.3%) (hazard ratio [HR], 0.94; 95% CI, 0.68-1.29). The same was observed for 5-year DFS: TG (46.0%; 95% CI, 35.9-55.5%) versus SG (45.3%; 95% CI, 34.3-55.6%) (HR, 0.97; 95% CI, 0.70-1.34). CONCLUSIONS At 5 years, SG was not associated with worse OS and DFS than TG for distal PCC. Surgical morbidity was higher after TG. Subtotal gastrectomy is a valuable option for distal PCC gastric cancer.
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Affiliation(s)
- Mehdi Boubaddi
- Oeso-Gastric Surgery Unit, Department of Digestive Surgery, Magellan Center, Bordeaux University Hospital, Bordeaux, France
| | - Hugo Teixeira Farinha
- Oeso-Gastric Surgery Unit, Department of Digestive Surgery, Magellan Center, Bordeaux University Hospital, Bordeaux, France
- Department of Visceral Surgery, University Hospital of Lausanne, CHUV, Lausanne, Switzerland
| | - Céline Lambert
- Biostatistics Unit, DRCI, CHU Clermont-Ferrand, Clermont-Ferrand, France
- Department of Digestive Surgery, CHU Clermont-Ferrand, Clermont-Ferrand, France
| | - Bruno Pereira
- Biostatistics Unit, DRCI, CHU Clermont-Ferrand, Clermont-Ferrand, France
- Department of Digestive Surgery, CHU Clermont-Ferrand, Clermont-Ferrand, France
| | - Guillaume Piessen
- Department of Digestive and Oncological Surgery, Claude Huriez University Hospital, Lille, France
| | - Monica Gualtierotti
- Division of Minimally Invasive Surgical Oncology, Niguarda Cancer Center, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Thibault Voron
- Department of General and Digestive Surgery, Saint-Antoine Hospital, Paris, France
| | - Styliani Mantziari
- Department of Visceral Surgery, University Hospital of Lausanne, CHUV, Lausanne, Switzerland
| | - Denis Pezet
- Bordeaux University Hospital, U1312 Bordeaux Institute of Oncology, INSERM, Bordeaux, France
| | - Caroline Gronnier
- Oeso-Gastric Surgery Unit, Department of Digestive Surgery, Magellan Center, Bordeaux University Hospital, Bordeaux, France.
- Bordeaux University Hospital, U1312 Bordeaux Institute of Oncology, INSERM, Bordeaux, France.
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11
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Song X, Xie Y, Lou Y. Who are optimal candidates for primary tumor resection in patients with metastatic gastric adenocarcinoma? A population-based study. PLoS One 2024; 19:e0292895. [PMID: 38266030 PMCID: PMC10807831 DOI: 10.1371/journal.pone.0292895] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Accepted: 10/01/2023] [Indexed: 01/26/2024] Open
Abstract
BACKGROUND The research aimed to construct a novel predictive nomogram to identify specific metastatic gastric adenocarcinoma (mGAC) populations who could benefit from primary tumor resection (PTR). METHOD Patients with mGAC were included in the SEER database and divided into PTR and non-PTR groups. The Kaplan-Meier analysis, propensity score matching (PSM), least absolute shrink and selection operator (LASSO) regression, multivariable logistic regression, and multivariate Cox regression methods were then used. Finally, the prediction nomograms were built and tested. RESULTS 3185 patients with mGAC were enrolled. Among the patients, 679 cases underwent PTR while the other 2506 patients didn't receive PTR. After PSM, the patients in the PTR group presented longer median overall survival (15.0 vs. 7.0 months, p < 0.001). Among the PTR group, 307 (72.9%) patients obtained longer overall survival than seven months (beneficial group). Then the LASSO logistic regression was performed, and gender, grade, T stage, N stage, pathology, and chemotherapy were included to construct the nomogram. In both the training and validation cohorts, the nomogram exhibited good discrimination (AUC: 0.761 and 0.753, respectively). Furthermore, the other nomogram was constructed to predict 3-, 6-, and 12-month cancer-specific survival based on the variables from the multivariate Cox analysis. The 3-, 6-, and 12-month AUC values were 0.794, 0.739, and 0.698 in the training cohort, and 0.805, 0.759, and 0.695 in the validation cohorts. The calibration curves demonstrated relatively good consistency between the predicted and observed probabilities of survival in two nomograms. The models' clinical utility was revealed through decision curve analysis. CONCLUSION The benefit nomogram could guide surgeons in decision-making and selecting optimal candidates for PTR among mGAC patients. And the prognostic nomogram presented great prediction ability for these patients.
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Affiliation(s)
- Xue Song
- Department of Respiratory and Critical Care Medicine, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China
| | - Yangyang Xie
- Department of General Surgery, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China
| | - Yafang Lou
- Department of Respiratory and Critical Care Medicine, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China
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12
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Park SY, Park JH, Yang JW, Jung EJ, Ju YT, Jeong CY, Kim JY, Park T, Park M, Lee YJ, Jeong SH. HTATIP2 Overexpression was Associated With a Good Prognosis in Gastric Cancer. Technol Cancer Res Treat 2024; 23:15330338231187254. [PMID: 38303513 PMCID: PMC10838032 DOI: 10.1177/15330338231187254] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2022] [Revised: 04/27/2023] [Accepted: 06/23/2023] [Indexed: 02/03/2024] Open
Abstract
Introduction: The purpose of this study was to compare the transcriptomes of poorly cohesive carcinoma (PCC; diffuse-type) and well-differentiated tubular adenocarcinoma (WD; intestinal-type) using gastric cancer (GC) tissues and cell lines and to evaluate the prognostic role of HIV-1 Tat Interactive Protein 2 (HTATIP2). Materials and Methods: We performed next-generation sequencing with 8 GC surgical samples (5 WD and 3 PCC) and 3 GC cell lines (1 WD: MKN74, and 2 PCC: KATOIII and SNU601). Immunohistochemistry was used to validate HTATIP2 expression. We performed functional analysis by HTATIP2 overexpression (OE). Kaplan-Meier survival plots and the PrognoScan database were used for survival analysis. Results: The genes with significantly reduced expression in PCC versus WD (in both tissues and cell lines) were HTATIP2, ESRP1, GRHL2, ARHGEF16, CKAP2L, and ZNF724. According to immunohistochemical staining, the HTATIP2-OE group had significantly higher number of patients with early GC (EGC) (T1) (P = .024), less lymph node (LN) metastasis (P = .008), and low TNMA stage (P = .017) than HTATIP2 underexpression (UE) group. Better survival rates were confirmed in the HTATIP2 OE group by Kaplan-Meir survival and PrognoScan analysis. In vitro, HTATIP2-OE in KATO III cells caused a significant decrease in cancer cell migration and invasion. Decreased Snail and Slug expression in HTATIP2 OE cells suggested that epithelial-mesenchymal transition is involved in this process. Conclusion: HTATIP2 might be a good prognostic marker and a candidate target for GC treatment.
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Affiliation(s)
- Sun Yi Park
- Department of Surgery, Gyeongsang National University Hospital and Gyeongsang National University College of Medicine, Jinju, South Korea
| | - Ji-Ho Park
- Department of Surgery, Gyeongsang National University Hospital and Gyeongsang National University College of Medicine, Jinju, South Korea
| | - Jung Wook Yang
- Department of Pathology, Gyeongsang National University Hospital and Gyeongsang National University College of Medicine, Jinju, South Korea
| | - Eun-Jung Jung
- Department of Surgery, Gyeongsang National University Changwon Hospital and Gyeongsang National University College of Medicine, Jinju, South Korea
| | - Young-Tae Ju
- Department of Surgery, Gyeongsang National University Hospital and Gyeongsang National University College of Medicine, Jinju, South Korea
| | - Chi-Young Jeong
- Department of Surgery, Gyeongsang National University Hospital and Gyeongsang National University College of Medicine, Jinju, South Korea
| | - Ju-Yeon Kim
- Department of Surgery, Gyeongsang National University Hospital and Gyeongsang National University College of Medicine, Jinju, South Korea
| | - Taejin Park
- Department of Surgery, Gyeongsang National University Changwon Hospital and Gyeongsang National University College of Medicine, Jinju, South Korea
| | - Miyeong Park
- Department of Anesthesiology, Gyeongsang National University Changwon Hospital, Changwon, South Korea
| | - Young-Joon Lee
- Department of Surgery, Gyeongsang National University Hospital and Gyeongsang National University College of Medicine, Jinju, South Korea
| | - Sang-Ho Jeong
- Department of Pathology, Gyeongsang National University Hospital and Gyeongsang National University College of Medicine, Jinju, South Korea
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13
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Dal Cero M, Bencivenga M, Liu DHW, Sacco M, Alloggio M, Kerckhoffs KGP, Filippini F, Saragoni L, Iglesias M, Tomezzoli A, Carneiro F, Grabsch HI, Verlato G, Torroni L, Piessen G, Pera M, de Manzoni G. Clinical Features of Gastric Signet Ring Cell Cancer: Results from a Systematic Review and Meta-Analysis. Cancers (Basel) 2023; 15:5191. [PMID: 37958365 PMCID: PMC10647446 DOI: 10.3390/cancers15215191] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2023] [Revised: 10/17/2023] [Accepted: 10/26/2023] [Indexed: 11/15/2023] Open
Abstract
BACKGROUND Conflicting results about the prognostic relevance of signet ring cell histology in gastric cancer have been reported. We aimed to perform a meta-analysis focusing on the clinicopathological features and prognosis of this subgroup of cancer compared with other histologies. METHODS A systematic literature search in the PubMed database was conducted, including all publications up to 1 October 2021. A meta-analysis comparing the results of the studies was performed. RESULTS A total of 2062 studies referring to gastric cancer with signet ring cell histology were identified, of which 262 studies reported on its relationship with clinical information. Of these, 74 were suitable to be included in the meta-analysis. A slightly lower risk of developing nodal metastases in signet ring cell tumours compared to other histotypes was found (especially to undifferentiated/poorly differentiated/mucinous and mixed histotypes); the lower risk was more evident in early and slightly increased in advanced gastric cancer. Survival tended to be better in early stage signet ring cell cancer compared to other histotypes; no differences were shown in advanced stages, and survival was poorer in metastatic patients. In the subgroup analysis, survival in signet ring cell cancer was slightly worse compared to non-signet ring cell cancer and differentiated/well-to-moderately differentiated adenocarcinoma. CONCLUSIONS Most of the conflicting results in signet ring cell gastric cancer literature could be derived from the lack of standardisation in their classification and the comparison with the different subtypes of gastric cancer. There is a critical need to strive for a standardised classification system for gastric cancer, fostering clarity and coherence in the forthcoming research and clinical applications.
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Affiliation(s)
- Mariagiulia Dal Cero
- General and Upper GI Surgery Division, Department of Surgery, University of Verona, Borgo Trento Hospital, Piazzale Stefani 1, 37124 Verona, Italy; (M.D.C.)
- Section of Gastrointestinal Surgery, Hospital Universitario del Mar, Hospital del Mar Medical Research Institute (IMIM), Department of Surgery, Universitat Autònoma de Barcelona, 08003 Barcelona, Spain
| | - Maria Bencivenga
- General and Upper GI Surgery Division, Department of Surgery, University of Verona, Borgo Trento Hospital, Piazzale Stefani 1, 37124 Verona, Italy; (M.D.C.)
| | - Drolaiz H. W. Liu
- Department of Pathology, GROW School for Oncology and Reproduction, Maastricht University Medical Center, 6229 HX Maastricht, The Netherlands
- Institute of Clinical Pathology and Molecular Pathology, Kepler University Hospital and Johannes Kepler University, 4021 Linz, Austria
| | - Michele Sacco
- General and Upper GI Surgery Division, Department of Surgery, University of Verona, Borgo Trento Hospital, Piazzale Stefani 1, 37124 Verona, Italy; (M.D.C.)
| | - Mariella Alloggio
- General and Upper GI Surgery Division, Department of Surgery, University of Verona, Borgo Trento Hospital, Piazzale Stefani 1, 37124 Verona, Italy; (M.D.C.)
| | - Kelly G. P. Kerckhoffs
- Department of Pathology, GROW School for Oncology and Reproduction, Maastricht University Medical Center, 6229 HX Maastricht, The Netherlands
- Department of Pathology, VieCuri Medical Centre, 5912 BL Venlo, The Netherlands
| | - Federica Filippini
- General and Upper GI Surgery Division, Department of Surgery, University of Verona, Borgo Trento Hospital, Piazzale Stefani 1, 37124 Verona, Italy; (M.D.C.)
| | - Luca Saragoni
- Pathology Unit, Morgagni-Pierantoni Hospital, 47100 Forlì, Italy
| | - Mar Iglesias
- Department of Pathology, Hospital Universitario del Mar, Hospital del Mar Medical Research Institute (IMIM), 08003 Barcelona, Spain
| | - Anna Tomezzoli
- Department of Pathology, Verona University Hospital, 37134 Verona, Italy
| | - Fátima Carneiro
- Department of Pathology, Medical Faculty of the University of Porto/Centro Hospitalar Universitário São João and Ipatimup/i3S, 4200-319 Porto, Portugal
| | - Heike I. Grabsch
- Department of Pathology, GROW School for Oncology and Reproduction, Maastricht University Medical Center, 6229 HX Maastricht, The Netherlands
- Division of Pathology and Data Analytics, Leeds Institute of Medical Research at St. James’s, University of Leeds, Leeds LS2 9JT, UK
| | - Giuseppe Verlato
- Unit of Epidemiology and Medical Statistics, Department of Diagnostics and Public Health, University of Verona, 37126 Verona, Italy
| | - Lorena Torroni
- Unit of Epidemiology and Medical Statistics, Department of Diagnostics and Public Health, University of Verona, 37126 Verona, Italy
| | - Guillaume Piessen
- Department of Digestive and Oncological Surgery, Lille University Hospital, 59000 Lille, France
| | - Manuel Pera
- Section of Gastrointestinal Surgery, Hospital Universitario del Mar, Hospital del Mar Medical Research Institute (IMIM), Department of Surgery, Universitat Autònoma de Barcelona, 08003 Barcelona, Spain
| | - Giovanni de Manzoni
- General and Upper GI Surgery Division, Department of Surgery, University of Verona, Borgo Trento Hospital, Piazzale Stefani 1, 37124 Verona, Italy; (M.D.C.)
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14
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Baek JH, Kang BW, Kang H, Cho M, Kwon OK, Park JY, Park KB, Seo AN, Kim JG. Clinical implications and chemo-sensitivity of adjuvant chemotherapy in patients with poorly cohesive cells-gastric cancer. Cancer Chemother Pharmacol 2023; 92:279-290. [PMID: 37480406 DOI: 10.1007/s00280-023-04564-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2023] [Accepted: 07/01/2023] [Indexed: 07/24/2023]
Abstract
PURPOSE Poorly cohesive cells-gastric cancer (PCC-GC) represents distinct features within the GC spectrum. The present study investigated the clinicopathologic characteristics and chemo-sensitivity for a relatively large cohort of PCC-GC patients. MATERIALS AND METHODS A total of 268 patients diagnosed with stage II or III PCC-GC were included. GC cell lines were also analyzed for drug sensitivity to 5-fluorouracil (5-FU) and oxaliplatin in vitro. RESULTS One hundred fifteen (42.9%) patients were stage II and 153 (57.1%) were stage III. Two hundred twenty-three (83.2%) patients received adjuvant therapy. Among these patients, 139 (62.3%) received CAPOX and 84 (37.7%) received S-1. With a median follow-up of 38.9 (1.6-137.8) months, the estimated 5-year disease-free survival (DFS) and overall survival (OS) rates were 52.3% and 61.0%, respectively. In the univariate analysis, survival was significantly better in the adjuvant chemotherapy group than in the surgery only group. In the subgroup analysis, there was no significant difference in DFS or OS between the types of adjuvant chemotherapy for either disease stage. In vitro cell line analysis, different responses to 5-FU and oxaliplatin were observed in SRC and non-SRC, where the treatment in KATOIII cell lines with oxaliplatin had less effect at a higher concentration compared to non-SRC cell lines. CONCLUSION The current study found that adjuvant chemotherapy was not significantly associated with survival benefit for patients with resected stage II and III PCC-GC. Plus, S-1 showed numerically longer DFS and OS compared to CAPOX in PCC-GC patients, although no significant in the multivariate analysis.
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Affiliation(s)
- Jin Ho Baek
- Department of Oncology/Hematology, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Kyungpook National University Cancer Research Institute, 807 Hoguk-ro, Buk-gu, Daegu, 41404, Republic of Korea
| | - Byung Woog Kang
- Department of Oncology/Hematology, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Kyungpook National University Cancer Research Institute, 807 Hoguk-ro, Buk-gu, Daegu, 41404, Republic of Korea
| | - Hyojeung Kang
- College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, Republic of Korea
| | - Miyeon Cho
- College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, Republic of Korea
| | - Oh Kyoung Kwon
- Department of Surgery, School of Medicine, Kyungpook National University Chilgok Hospital, Kyungpook National University, Daegu, Republic of Korea
| | - Ji Yeon Park
- Department of Surgery, School of Medicine, Kyungpook National University Chilgok Hospital, Kyungpook National University, Daegu, Republic of Korea
| | - Ki Bum Park
- Department of Surgery, School of Medicine, Kyungpook National University Chilgok Hospital, Kyungpook National University, Daegu, Republic of Korea
| | - An Na Seo
- Department of Pathology, School of Medicine, Kyungpook National University Chilgok Hospital, Kyungpook National University, Daegu, Republic of Korea
| | - Jong Gwang Kim
- Department of Oncology/Hematology, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Kyungpook National University Cancer Research Institute, 807 Hoguk-ro, Buk-gu, Daegu, 41404, Republic of Korea.
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15
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Liu D, Ding R, Wang L, Shi E, Li X, Zhang C, Zhang Y, Wang X. Novel nomogram to predict the overall survival of postoperative patients with gastric signet. BMC Gastroenterol 2023; 23:284. [PMID: 37587418 PMCID: PMC10429074 DOI: 10.1186/s12876-023-02915-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Accepted: 08/05/2023] [Indexed: 08/18/2023] Open
Abstract
BACKGROUND The TNM staging system cannot accurately predict the prognosis of postoperative gastric signet ring cell carcinoma (GSRC) given its unique biological behavior, epidemiological features, and various prognostic factors. Therefore, a reliable postoperative prognostic evaluation system for GSRC is required. This study aimed to establish a nomogram to predict the overall survival (OS) rate of postoperative patients with GSRC and validate it in the real world. METHODS Clinical data of postoperative patients with GSRC from 2002 to 2014 were collected from the Surveillance, Epidemiology, and End Results database and randomly assigned to training and internal validation sets at a 7:3 ratio. The external validation set used data from 124 postoperative patients with GSRC who were admitted to the Affiliated Tumor Hospital of Harbin Medical University between 2002 and 2014. The independent risk factors affecting OS were screened using univariate and multivariate analyses to construct a nomogram. The performance of the model was evaluated using the C-index, receiver operating characteristic curve (ROC), calibration curve, decision analysis (DCA) curve, and adjuvant chemotherapy decision analysis. RESULTS Univariate/multivariate analysis indicated that age, stage, T, M, regional nodes optimized (RNE), and lymph node metastasis rate (LNMR) were independent risk factors affecting prognosis. The C-indices of the training, internal validation, and external validation sets are 0.741, 0.741, and 0.786, respectively. The ROC curves for the first, third, and fifth years in three sets had higher areas under the curves, (training set, 0.782, 0.864, 0.883; internal validation set, 0.781, 0.863, 0.877; external validation set, 0.819, 0.863, 0.835). The calibration curve showed high consistency between the nomogram-predicted 1-, 3-, and 5-year OS and the actual OS in the three queues. The DCA curve indicated that applying the nomogram enhanced the net clinical benefits. The nomogram effectively distinguished patients in each subgroup into high- and low-risk groups. Adjuvant chemotherapy can significantly improve OS in high-risk group (P = 0.034), while the presence or absence of adjuvant chemotherapy in low-risk group has no significant impact on OS (P = 0.192). CONCLUSIONS The nomogram can effectively predict the OS of patients with GSRC and may help doctors make personalized prognostic judgments and clinical treatment decisions.
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Affiliation(s)
- Donghui Liu
- School of Life Science and Technology, Harbin Institute of Technology, Harbin, China
- Department of Oncology, Heilongjiang Provincial Hospital, Harbin, China
| | - Ran Ding
- Department of Oncology, Heilongjiang Provincial Hospital, Harbin, China
| | - Liru Wang
- Department of Oncology, Heilongjiang Provincial Hospital, Harbin, China
| | - Enhong Shi
- Department of Oncology, Heilongjiang Provincial Hospital, Harbin, China
| | - Xiaoxue Li
- Department of Oncology, Heilongjiang Provincial Hospital, Harbin, China
| | - Chenyao Zhang
- Department of Oncology, Heilongjiang Provincial Hospital, Harbin, China
| | - Yan Zhang
- School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.
| | - Xuyao Wang
- Department of Pharmacy, Harbin Second Hospital, Harbin, China.
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16
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Liang C, Liang Y, Ou B, Yuan L, Yuan S. Clinicopathological and prognostic features of Borrmann type IV gastric cancer versus other Borrmann types: A unique role of signet ring cell carcinoma. Saudi J Gastroenterol 2023; 29:240-250. [PMID: 37470667 PMCID: PMC10445496 DOI: 10.4103/sjg.sjg_469_22] [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: 10/31/2022] [Revised: 05/17/2023] [Accepted: 05/25/2023] [Indexed: 06/21/2023] Open
Abstract
Background Evidence specifically comparing the clinicopathology of Borrmann type IV (B-IV) gastric cancer with that of other Borrmann types is insufficient. Methods A total of 3130 patients with advanced gastric cancer who underwent gastrectomy from January 2001 to September 2017 were enrolled in the analysis. Logistic regression and survival analysis methodology were used to investigate factors associated with peritoneal metastasis and overall survival (OS). Results Of the total cohort, 264 (8.43%) patients were B-IV type, 1752 (55.97%) were small-size other Borrmann types, and 1114 (35.59%) were large-size other Borrmann types. Signet ring cell carcinoma (SRC) was more common in B-IV types than in other Borrmann types (33.71% vs 11.42% vs 12.66%, P < 0.001). In B-IV gastric cancers, SRC was significantly associated with peritoneal metastasis (HR = 1.898, 95% CI = 1.112 ~ 3.241, P = 0.019) and poorer OS (HR = 1.492, 95% CI = 1.088 ~ 2.045, P = 0.013) in multivariable analysis. Furthermore, stratified analysis revealed that SRC had worse survival than adenocarcinoma in the B-IV subgroups, with locally advanced stages (stages II ~ III) or negative surgical margins (all P < 0.05). In contrast, SRC failed to be significantly associated with peritoneal metastasis and poor OS in other Borrmann types (all P > 0.05). Conclusion SRC was more common in B-IV gastric cancer than in other Borrmann types. It was significantly associated with peritoneal metastasis and poorer OS in the B-IV type but not in other Borrmann types. As a unique prognostic factor for B-IV gastric cancer, SRC might help evaluate risk stratification and optimize treatment for this entity, especially for patients with locally advanced stages or R0 resection.
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Affiliation(s)
- Chengcai Liang
- Department of Gastric Surgery, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
- Department of Gastric Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Yao Liang
- Department of Gastric Surgery, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
- Department of Gastric Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Biyi Ou
- Department of Gastric Surgery, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
- Department of Gastric Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Lei Yuan
- Department of Gastric Surgery, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
- Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Shuqiang Yuan
- Department of Gastric Surgery, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
- Department of Gastric Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, China
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17
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Koseki Y, Hatakeyama K, Terashima M, Nagashima T, Urakami K, Ohshima K, Aizawa D, Sugino T, Furukawa K, Fujiya K, Tanizawa Y, Bando E, Okamura Y, Akiyama Y, Yamaguchi K. Molecular profile of poorly cohesive gastric carcinoma with special reference to survival. Gastric Cancer 2023; 26:553-564. [PMID: 37036539 DOI: 10.1007/s10120-023-01390-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2022] [Accepted: 04/01/2023] [Indexed: 04/11/2023]
Abstract
BACKGROUND Patients with poorly cohesive gastric carcinoma (PCC) are known to have poor survival. However, detailed molecular biology of PCC has not been elucidated, except for mutations in CDH1 and RHOA. Additionally, the molecular profiles of signet-ring cell carcinoma (SRC) have not been fully investigated. We aimed to investigate the association between molecular profiles and survival in PCC and PCC subtypes. METHODS The present study included 455 patients with gastric adenocarcinoma underwent radical gastrectomy. Whole-exome sequencing and gene expression profiling were conducted. Patients were classified according to the WHO classification as PCC or non-PCC, with PCC being further classified into SRC, combined, and PCC not-otherwise-specified (NOS). Clinicopathological factors and survival were compared with molecular profiles. RESULTS Of the patients, 159 were classified with PCC, while 296 were classified with non-PCC. Among PCC, 44 were classified with SRC, 64 with combined, and 51 with PCC-NOS. Mutations in CDH1 and RHOA were remarkably more frequent in PCC than in non-PCC. PCC had worse overall survival (OS) and disease-specific survival (DSS) compared to non-PCC. For PCC, the SRC group had good OS and DSS, whereas PCC-NOS classification with CDH1 mutations was associated with extremely poor survival. In the PCC-NOS and combined groups, patients with mutations in the extracellular domain 1 of CDH1 had poor survival. CONCLUSIONS Our findings suggest that PCC has poorer survival than non-PCC. Accumulation of CDH1 and RHOA mutations are unique profiles in PCC. Among PCC, CDH1 mutations may play a crucial role in the survival of non-SRC PCC.
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Affiliation(s)
- Yusuke Koseki
- Division of Gastric Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-Cho, Sunto-Gun, Shizuoka, 411-8777, Japan
- Division of Digestive Surgery, Department of Surgery, School of Medicine, Nihon University, Tokyo, Japan
| | - Keiichi Hatakeyama
- Cancer Multiomics Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan
| | - Masanori Terashima
- Division of Gastric Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-Cho, Sunto-Gun, Shizuoka, 411-8777, Japan.
| | - Takeshi Nagashima
- Cancer Diagnostics Research Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan
- SRL Inc., Tokyo, Japan
| | - Kenichi Urakami
- Cancer Diagnostics Research Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan
| | - Keiichi Ohshima
- Medical Genetics Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan
| | - Daisuke Aizawa
- Division of Pathology, Shizuoka Cancer Center, Shizuoka, Japan
| | - Takashi Sugino
- Division of Pathology, Shizuoka Cancer Center, Shizuoka, Japan
| | - Kenichiro Furukawa
- Division of Gastric Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-Cho, Sunto-Gun, Shizuoka, 411-8777, Japan
| | - Keiichi Fujiya
- Division of Gastric Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-Cho, Sunto-Gun, Shizuoka, 411-8777, Japan
| | - Yutaka Tanizawa
- Division of Gastric Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-Cho, Sunto-Gun, Shizuoka, 411-8777, Japan
| | - Etsuro Bando
- Division of Gastric Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-Cho, Sunto-Gun, Shizuoka, 411-8777, Japan
| | - Yukiyasu Okamura
- Division of Digestive Surgery, Department of Surgery, School of Medicine, Nihon University, Tokyo, Japan
| | - Yasuto Akiyama
- Immunotherapy Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan
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Tian HK, Zhang Z, Ning ZK, Liu J, Liu ZT, Huang HY, Zong Z, Li H. Clinicopathological characteristics and prognosis of gastric signet ring cell carcinoma. World J Clin Cases 2022; 10:10451-10466. [PMID: 36312481 PMCID: PMC9602248 DOI: 10.12998/wjcc.v10.i29.10451] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2022] [Revised: 07/21/2022] [Accepted: 08/31/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND The clinicopathological features and prognosis of gastric signet ring cell carcinoma (GSRC) remain controversial, particularly with regard to sensitivity to postoperative adjuvant therapy.
AIM To compare the pathological features of GSRC with those of gastric adenocarcinoma of different degrees of differentiation and the differences in survival prognosis between the different disease processes.
METHODS By screening gastric cancer patients from 2010 to 2015 in the database of Surveillance, Epidemiology and End Results, and collecting the clinicopathological and prognostic data of gastric cancer patients who underwent surgery from January 2014 to December 2016 in the Second Affiliated Hospital of Nanchang University, we analyzed the general pathological characteristics of GSRC by the chi-square test. Univariate and multivariate analyses were conducted to compare the factors affecting the survival and prognosis of early and advanced gastric adenocarcinoma. The Kaplan-Meier curves were plotted to reveal the survival difference between early and advanced GSRC and different differentiated types of gastric adenocarcinoma. The prognosis model of advanced GSRC was established with R software, and the area under curve (AUC) and C-index were used to assess the accuracy of the model.
RESULTS Analysis of pathological features revealed that signet ring-cell carcinoma (SRC) was more frequently seen in younger (< 60 years), female, and White patients compared to non-SRC patients. SRC was less commonly associated with early gastric cancer (EGC) (23.60% vs 39.10%), lower N0 (38.61% vs 61.03%), and larger tumour sizes > 5 cm (31.15% vs 27.10%) compared to the differentiated type, while the opposite was true compared to the undifferentiated type. Survival prognostic analysis found no significant difference in the prognosis of SRC patients among EGC patients. In contrast, among advanced gastric cancer (AGC) patients, the prognosis of SRC patients was correlated with age, race, tumour size, AJCC stage, T-stage, and postoperative adjuvant therapy. The predictive model showed that the 3-year AUC was 0.787, 5-year AUC was 0.806, and C-index was 0.766. Compared to non-SRC patients, patients with SRC had a better prognosis in EGC [hazard ratio (HR): 0.626, 95% confidence interval (CI): 0.427-0.919, P < 0.05] and a worse prognosis in AGC (HR: 1.139, 95%CI: 1.030-1.258, P < 0.05). When non-SRC was divided into differentiated and undifferentiated types for comparison, it was found that in EGC, SRC had a better prognosis than differentiated and undifferentiated types, while there was no significant difference between differentiated and undifferentiated types. In AGC, there was no significant difference in prognosis between SRC and undifferentiated types, both of which were worse than differentiated types. A prognostic analysis of postoperative adjuvant therapy for SRC in patients with AGC revealed that adjuvant postoperative radiotherapy or chemotherapy significantly improved patient survival (34.6% and 36.2% vs 18.6%, P < 0.05).
CONCLUSION The prognosis of SRC is better than that of undifferentiated type, especially in EGC, and its prognosis is even better than that of differentiated type. SRC patients can benefit from early detection, surgical resection, and aggressive adjuvant therapy.
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Affiliation(s)
- Hua-Kai Tian
- Department of General Surgery, First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Zuo Zhang
- Department of Obstetrics and Gynecology, Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Zhi-Kun Ning
- Department of Day Ward, First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Jiang Liu
- Department of Gastrointestinal Surgery, Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Zi-Tao Liu
- Department of Gastrointestinal Surgery, Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Hao-Yu Huang
- Department of Gastrointestinal Surgery, Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Zhen Zong
- Department of Gastrointestinal Surgery, Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Hui Li
- Department of Rheumatology and Immunology, First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
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Lei ZN, Teng QX, Tian Q, Chen W, Xie Y, Wu K, Zeng Q, Zeng L, Pan Y, Chen ZS, He Y. Signaling pathways and therapeutic interventions in gastric cancer. Signal Transduct Target Ther 2022; 7:358. [PMID: 36209270 PMCID: PMC9547882 DOI: 10.1038/s41392-022-01190-w] [Citation(s) in RCA: 121] [Impact Index Per Article: 40.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2022] [Revised: 08/14/2022] [Accepted: 09/07/2022] [Indexed: 11/23/2022] Open
Abstract
Gastric cancer (GC) ranks fifth in global cancer diagnosis and fourth in cancer-related death. Despite tremendous progress in diagnosis and therapeutic strategies and significant improvements in patient survival, the low malignancy stage is relatively asymptomatic and many GC cases are diagnosed at advanced stages, which leads to unsatisfactory prognosis and high recurrence rates. With the recent advances in genome analysis, biomarkers have been identified that have clinical importance for GC diagnosis, treatment, and prognosis. Modern molecular classifications have uncovered the vital roles that signaling pathways, including EGFR/HER2, p53, PI3K, immune checkpoint pathways, and cell adhesion signaling molecules, play in GC tumorigenesis, progression, metastasis, and therapeutic responsiveness. These biomarkers and molecular classifications open the way for more precise diagnoses and treatments for GC patients. Nevertheless, the relative significance, temporal activation, interaction with GC risk factors, and crosstalk between these signaling pathways in GC are not well understood. Here, we review the regulatory roles of signaling pathways in GC potential biomarkers, and therapeutic targets with an emphasis on recent discoveries. Current therapies, including signaling-based and immunotherapies exploited in the past decade, and the development of treatment for GC, particularly the challenges in developing precision medications, are discussed. These advances provide a direction for the integration of clinical, molecular, and genomic profiles to improve GC diagnosis and treatments.
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Affiliation(s)
- Zi-Ning Lei
- Guangdong Provincial Key Laboratory of Digestive Cancer Research, Digestive Diseases Center, Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-Sen University, 518107, Shenzhen, Guangdong, China
- Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, 11439, USA
| | - Qiu-Xu Teng
- Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, 11439, USA
| | - Qin Tian
- Guangdong Provincial Key Laboratory of Digestive Cancer Research, Digestive Diseases Center, Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-Sen University, 518107, Shenzhen, Guangdong, China
| | - Wei Chen
- Guangdong Provincial Key Laboratory of Digestive Cancer Research, Digestive Diseases Center, Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-Sen University, 518107, Shenzhen, Guangdong, China
| | - Yuhao Xie
- Institute for Biotechnology, St. John's University, Queens, NY, 11439, USA
| | - Kaiming Wu
- Guangdong Provincial Key Laboratory of Digestive Cancer Research, Digestive Diseases Center, Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-Sen University, 518107, Shenzhen, Guangdong, China
| | - Qianlin Zeng
- Guangdong Provincial Key Laboratory of Digestive Cancer Research, Digestive Diseases Center, Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-Sen University, 518107, Shenzhen, Guangdong, China
| | - Leli Zeng
- Guangdong Provincial Key Laboratory of Digestive Cancer Research, Digestive Diseases Center, Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-Sen University, 518107, Shenzhen, Guangdong, China.
| | - Yihang Pan
- Guangdong Provincial Key Laboratory of Digestive Cancer Research, Digestive Diseases Center, Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-Sen University, 518107, Shenzhen, Guangdong, China.
| | - Zhe-Sheng Chen
- Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, 11439, USA.
- Institute for Biotechnology, St. John's University, Queens, NY, 11439, USA.
| | - Yulong He
- Guangdong Provincial Key Laboratory of Digestive Cancer Research, Digestive Diseases Center, Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-Sen University, 518107, Shenzhen, Guangdong, China.
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20
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Yu C, Zhou Z, Liu B, Yao D, Huang Y, Wang P, Li Y. Pathological Nodal Staging Score for Gastric Signet Ring Cell Carcinoma: A Clinical Tool of Adequate Nodal Staging. Diagnostics (Basel) 2022; 12:diagnostics12102289. [PMID: 36291978 PMCID: PMC9600920 DOI: 10.3390/diagnostics12102289] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2022] [Revised: 09/11/2022] [Accepted: 09/20/2022] [Indexed: 11/16/2022] Open
Abstract
Background: Gastric signet ring cell carcinoma (GSRCC) is a subset of gastric cancer with distinct histological and inconsistent prognosis outcome. Currently, the association between the adequate regional lymph node and proper nodal staging in GSRCC is rarely noticed. Materials and methods: Clinical data of GSRCC were retrieved from the Surveillance, Epidemiology, and End Results database. Beta-binomial distribution model was employed for the estimation of the probability of missing nodal disease, followed by the development of a nodal staging score (NSS). Results: A total of 561 GSRCC patients were included in this study, with 193 in lymph node-negative and 368 in lymph node-positive diagnoses. As the number of examined lymph nodes increased, the probability of missing nodal disease decreased rapidly, with T stage-specific curves. The probability of missing nodal disease in T4 was lower than that in T1. NSS calculation indicated that T1 stage patients commonly had NSS > 0.8. However, with the NSS of T2−T4 to reach 0.8, the number of examined lymph node was required to be larger than 12 in T2, 17 in T3 and 27 in T4. NSS ≥ 0.75 (quantile 75%) subgroup in T2−T4 subgroups tended to have better outcome; however, without significant prognostic value. Conclusions: NSS is served as a reliable and feasible tool in adequate nodal staging of GSRCC with statistical basis and provides further evidence for clinical decision making.
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21
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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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22
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Guo Y, Wang Q, Tian Q, Bo C, Li N, Zhang S, Li P. Clinicopathological Features and Prognostic-Related Risk Factors of Gastric Signet Ring Cell Carcinoma: A Meta-Analysis. COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE 2022; 2022:3473445. [PMID: 36035278 PMCID: PMC9410921 DOI: 10.1155/2022/3473445] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Revised: 07/06/2022] [Accepted: 07/17/2022] [Indexed: 11/23/2022]
Abstract
Background Gastric signet ring cell carcinoma (SRCC) has shown a growth growing trend worldwide, but its clinicopathological features and prognostic-related risk factors have not been systematically studied. This systematic review was devoted to this. Method PubMed, Embase, Cochrane Library, and Web of Science databases were retrieved, and retrospective cohort studies comparing clinicopathological features and related risk factors in SRCC patients were included. Results In SRCC patient population, males were more than females (male, OR = 1.38, 95% CI: 1.20-1.60); N3 patients were more than N0-2 patients (N0-2, OR = 3.19, 95% CI: 1.98-5.15); M1 patients were more than M0 patients (M0, OR = 3.30, 95% CI: 1.88-5.80); patients with tumor > 5 cm were more than those with tumor (≤5 cm, OR = 7.36, 95% CI: 1.33-40.60). Patients with age < 60 years (age ≥ 60 years, OR = 1.03, 95% CI: 1.01-1.05), lymphatic vessel invasion (no, OR = 1.74, 95% CI: 1.03-2.45), T2 (T1, OR = 1.17, 95% CI: 1.07-1.28) and T4 (T1, OR = 2.55, 95% CI: 2.30-2.81) stages, and N1 (N0, OR = 1.73, 95% CI: 1.08-2.38), N2 (N0, OR = 2.24, 95% CI: 1.12-3.36), and N3 (N0, OR = 3.45, 95% CI: 1.58-5.32) stages had higher hazard ratio (HR). Conclusion SRCC may occur frequently in male. Age, lymphatic vessel invasion, TN, and M stage may be risk factors for poor prognoses of SRCC patients.
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Affiliation(s)
- Ying Guo
- Department of Oncology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China
| | - Qian Wang
- Department of Oncology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China
| | - Qing Tian
- Thoracic Surgery Department, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China
| | - Changwen Bo
- Department of Oncology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China
| | - Na Li
- Department of Oncology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China
| | - Sujing Zhang
- Department of Oncology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China
| | - Peishun Li
- Department of Oncology, Tengzhou Central People's Hospital, Tengzhou, Shandong 277500, China
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Allart M, Leroy F, Kim S, Sefrioui D, Nayeri M, Zaanan A, Rousseau B, Ben Abdelghani M, de la Fouchardière C, Cacheux W, Legros R, Louafi S, Tougeron D, Bouché O, Fares N, Roquin G, Bignon AL, Maillet M, Pozet A, Hautefeuille V. Metastatic colorectal carcinoma with signet-ring cells: Clinical, histological and molecular description from an Association des Gastro-Entérologues Oncologues (AGEO) French multicenter retrospective cohort. Dig Liver Dis 2022; 54:391-399. [PMID: 34384712 DOI: 10.1016/j.dld.2021.06.031] [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: 05/24/2021] [Revised: 06/21/2021] [Accepted: 06/27/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND Metastatic signet-ring cell colorectal carcinoma is rare. We analyzed its clinicopathological and molecular features, prognostic factors and chemosensitivity. METHODS Retrospective study from 2003 to 2017 in 31 French centers, divided into three groups: curative care (G1), chemotherapy alone (G2), and best supportive care (G3). RESULTS Tumors were most frequently in the proximal colon (46%), T4 (71%), and poorly differentiated (86%). The predominant metastatic site was peritoneum (69%). Microsatellite instability and BRAF mutation were found in 19% and 9% (mainly right-sided) of patients and RAS mutations in 23%. Median overall survival (mOS) of the patients (n = 204) was 10.1 months (95%CI: 7.9;12.8), 45.1 for G1 (n = 38), 10.9 for G2 (n = 112), and 1.8 months for G3 (n = 54). No difference in mOS was found when comparing tumor locations, percentage of signet-ring cell contingent and microsatellite status. In G1, relapse-free survival was 14 months (95%CI: 6.5-20.9). In G2, median progression-free survival (PFS) was 4.7 months (95%CI: 3.6;5.9]) with first-line treatment. Median PFS was higher with biological agents than without (5.0 vs 3.9 months, p = 0.016). CONCLUSIONS mSRCC has a poor prognosis with specific location and molecular alterations resulting in low chemosensitivity. Routine microsatellite analysis should be performed because of frequent MSI-high tumors in this population.
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Affiliation(s)
- Marion Allart
- Department of Gastroenterology and Digestive Oncology, Amiens University Hospital, Amiens, France
| | - Florence Leroy
- Department of Cancer Medicine, Gustave Roussy Institute, Villejuif, France
| | - Stephano Kim
- Department of Medical Oncology, Jean Minjoz University Hospital, Besançon, France
| | - David Sefrioui
- Department of Hepato-Gastroenterology, Rouen University Hospital, Rouen, France
| | - Mihane Nayeri
- Department of Digestive and Oncological Surgery, Lille University, Claude Huriez University Hospital, Lille, France
| | - Aziz Zaanan
- Department of Gastroenterology and Digestive Oncology, European Georges Pompidou Hospital, APHP, Univ. Paris, Paris, France
| | - Benoit Rousseau
- Department of Medical Oncology, Henri Mondor University Hospital - Créteil, Memorial Sloan Kettering Cancer Center, New York, United States of America
| | | | | | - Wulfran Cacheux
- Department of Medical Oncology, Private Hospital Pays de Savoie, Annemasse, France
| | - Romain Legros
- Department of Gastroenterology, Limoges University Hospital, Limoges, France
| | - Samy Louafi
- Department of Medical Oncology, Oncology Federation of Essonne - Corbeil-Essonnes, France
| | - David Tougeron
- Department of Gastroenterology, Poitiers University Hospital, Poitiers, France
| | - Olivier Bouché
- Department of Gastroenterology and Digestive Oncology, Reims University Hospital, Reims, France
| | - Nadim Fares
- Department of Hepato-Gastroenterology, Toulouse University Hospital, Toulouse, France
| | - Guillaume Roquin
- Department of Gastroenterology and Digestive Oncology, Angers University Hospital, Angers, France
| | - Anne Laure Bignon
- Department of Hepato-Gastroenterology and Nutrition, Caen University Hospital, Caen, France
| | - Marianne Maillet
- Department of Gastroenterology, Saint Louis Hospital, APHP, Paris, France
| | - Astrid Pozet
- Methodology and Quality of Life in Oncology Unit, INSERM UMR 1098, Besançon University Hospital, Besançon, France
| | - Vincent Hautefeuille
- Department of Gastroenterology and Digestive Oncology, Amiens University Hospital, Amiens, France.
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Nakamura K, Eto K, Iwagami S, Ogawa K, Sawayama H, Ishimoto T, Iwatsuki M, Baba Y, Miyamoto Y, Yoshida N, Baba H. Clinicopathological characteristics and prognosis of poorly cohesive cell subtype of gastric cancer. Int J Clin Oncol 2022; 27:512-519. [PMID: 35084597 DOI: 10.1007/s10147-021-02069-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Accepted: 10/31/2021] [Indexed: 11/30/2022]
Abstract
BACKGROUND The new World Health Organization (WHO) classification of gastric cancer includes a histological subtype of poorly cohesive carcinoma (PCC), which includes signet-ring cell (SRC) phenotype. We aimed to examine the concordance between preoperative clinical and postoperative histological diagnoses according to the 2010 WHO histological subtypes and to compare the prognoses of these subtypes. METHODS The study cohort comprised 665 patients who underwent gastrectomy from 2005 to 2019. Histological subtypes were classified into PCC-NOS (non-signet ring cell subtype), SRC, and non-PCC, which were defined by the predominant component in accordance with the 2010 WHO classification of gastric cancer. The concordance of clinical and pathological diagnosis was examined and clinicopathological characteristics and survival outcome of the three subtypes compared. RESULTS The cancers of 443 patients (66.7%) were classified as non-PCC, of 112 patients (16.8%) as PCC-NOS, and of 110 patients (16.5%) as SRC predominant subtypes. Significant differences in sex, age, tumor location, size, macroscopic type, and pathological TNM category (all P<0.05) were found. The concordance rate of preoperative and postoperative histological subtypes was significantly lower for poorly cohesive than other subtypes (P<0.0001). Preoperative stage tended to be underestimated for PCC-NOS subtype and these patients had poorer overall survival than those with the other two subtypes (P=0.005). Multivariate logistic regression analysis of overall survival showed that WHO histological subtype (PCC-NOS vs. non-PCC/SRC, HR: 1.64, 95% CI: 1.18-2.29, P=0.0034) was a significant independent prognostic factor. CONCLUSION Our results suggest that poorly cohesive carcinoma subtypes have different biological characteristics and prognoses.
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Affiliation(s)
- Kenichi Nakamura
- Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
| | - Kojiro Eto
- Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Shiro Iwagami
- Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Katsuhiro Ogawa
- Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Hiroshi Sawayama
- Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Takatsugu Ishimoto
- Gastrointestinal Cancer Biology, International Research Center for Medical Sciences, Kumamoto University, Kumamoto, 860-8556, Japan
| | - Masaaki Iwatsuki
- Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Yoshifumi Baba
- Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Yuji Miyamoto
- Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Naoya Yoshida
- Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
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Perrot-Applanat M, Pimpie C, Vacher S, Bieche I, Pocard M, Baud V. Differential Expression of Genes Involved in Metabolism and Immune Response in Diffuse and Intestinal Gastric Cancers, a Pilot Ptudy. Biomedicines 2022; 10:biomedicines10020240. [PMID: 35203450 PMCID: PMC8869420 DOI: 10.3390/biomedicines10020240] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Revised: 01/13/2022] [Accepted: 01/16/2022] [Indexed: 02/01/2023] Open
Abstract
Gastric cancer (GC) is one of the major causes of cancer-related mortality worldwide. The vast majority of GC cases are adenocarcinomas including intestinal and diffuse GC. The incidence of diffuse GCs, often associated with poor overall survival, has constantly increased in USA and Europe The molecular basis of diffuse GC aggressivity remains unclear. Using mRNA from diffuse and intestinal GC tumor samples of a Western cohort, this study reports the expression level of the immunomodulatory aryl-hydrocarbon receptor (AhR), and genes involved in immune suppression (PD1, PD-L1, PD-L2) and the early steps of tryptophan metabolism (IDO1, IDO2, TDO2). Strongly increased expression of IDO1 (p < 0.001) and PD1 (p < 0.003) was observed in the intestinal sub-type. The highest expression of IDO1 and PDL1 correlated with early clinical stage and absence of lymphatic invasion (×25 p = 0.004, ×3 p = 0.04, respectively). Our results suggest that kynurenine, produced by tryptophan catabolism, and AhR activation play a central role in creating an immunosuppressive environment. Correspondingly, as compared to intestinal GCs, expression levels of IDO1-TDO2 and PD-L1 were less prominent in diffuse GCs which also had less infiltration of immune cells, suggesting an inactive immune response in the advanced diffuse GC. Confirmation of these patterns of gene expression will require a larger cohort of early and advanced stages of diffuse GC samples.
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Affiliation(s)
- Martine Perrot-Applanat
- INSERM U1275, CAP Paris-Tech, Université de Paris, Lariboisiere Hospital, F-75010 Paris, France; (C.P.); (M.P.)
- Correspondence: (M.P.-A.); (V.B.)
| | - Cynthia Pimpie
- INSERM U1275, CAP Paris-Tech, Université de Paris, Lariboisiere Hospital, F-75010 Paris, France; (C.P.); (M.P.)
| | - Sophie Vacher
- Pharmacogenomics Unit-Institut Curie, Department of Genetics, Université de Paris, F-75005 Paris, France; (S.V.); (I.B.)
| | - Ivan Bieche
- Pharmacogenomics Unit-Institut Curie, Department of Genetics, Université de Paris, F-75005 Paris, France; (S.V.); (I.B.)
| | - Marc Pocard
- INSERM U1275, CAP Paris-Tech, Université de Paris, Lariboisiere Hospital, F-75010 Paris, France; (C.P.); (M.P.)
- Hepato-Biliary-Pancreatic Gastrointestinal Surgery and Liver Transplantation, AP-HP, Pitié Salpêtrière Hospital, F-75013 Paris, France
| | - Véronique Baud
- NF-kappaB, Différenciation et Cancer, Université de Paris, F-75006 Paris, France
- Correspondence: (M.P.-A.); (V.B.)
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26
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Li Y, Zhong Y, Xu Q, Zhu Z, Tian Y. Prognostic Significance of Signet Ring Cells in Gastric Cancer: The Higher Proportion, The Better Survival. Front Oncol 2021; 11:713587. [PMID: 34858807 PMCID: PMC8630623 DOI: 10.3389/fonc.2021.713587] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2021] [Accepted: 10/18/2021] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Due to the fact that the definition of gastric signet ring cell cancer (GSRC) was still controversial in the past decades, the prognosis affected by the proportion of signet ring cells within gastric cancer is uncertain. This study compared the clinicopathological features and prognosis of GSRC with the various proportions of signet ring cells. METHODS We collected GSRC cases without metastasis who underwent curative (R0) resection between 2011 and 2018. Individuals who were in the low-proportion signet ring cell group (LSRC, <50%) were matched to those who were in the high-proportion signet ring cell group (HSRC, >50%) through propensity score matching (1:1). We used Cox proportional hazard regression to calculate the adjusted hazard ratios (HR) and 95% confidence intervals (CI) and explored interactions with gender and stage. RESULTS We had 1:1 matched individuals including 231 cases from the LSRC group and 231 cases from the HSRC group. Patients with HSRC had a significantly higher overall survival rate in the multivariable model (aHR = 0.56, 95%CI = 0.38, 0.84) compared with those with LSRC. The association of HSRC appeared to be more substantial among individuals at early stage and N0 stage (p-interaction < 0.01). CONCLUSIONS This study confirms that GSRC with different proportions of signet ring cells could affect the survival of the patient. Further clinical studies should be developed in the future to provide an appropriate treatment strategy for GSRC.
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Affiliation(s)
- Yang Li
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yuxin Zhong
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Quan Xu
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhikai Zhu
- Center for Big Data, National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Yantao Tian
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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27
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Bonnot PE, Lintis A, Mercier F, Benzerdjeb N, Passot G, Pocard M, Meunier B, Bereder JM, Abboud K, Marchal F, Quenet F, Goere D, Msika S, Arvieux C, Pirro N, Wernert R, Rat P, Gagnière J, Lefevre JH, Courvoisier T, Kianmanesh R, Vaudoyer D, Rivoire M, Meeus P, Villeneuve L, Piessen G, Glehen O. Prognosis of poorly cohesive gastric cancer after complete cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy (CYTO-CHIP study). Br J Surg 2021; 108:1225-1235. [PMID: 34498666 DOI: 10.1093/bjs/znab200] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2021] [Accepted: 05/07/2021] [Indexed: 12/14/2022]
Abstract
BACKGROUND The incidence of gastric poorly cohesive carcinoma (PCC) is increasing. The prognosis for patients with peritoneal metastases remains poor and the role of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is controversial. The aim was to clarify the impact of gastric PCC with peritoneal metastases treated by CRS with or without HIPEC. METHODS All patients with peritoneal metastases from gastric cancer treated with CRS with or without HIPEC, in 19 French centres, between 1989 and 2014, were identified from institutional databases. Clinicopathological characteristics and outcomes were compared between PCC and non-PCC subtypes, and the possible benefit of HIPEC was assessed. RESULTS In total, 277 patients were included (188 PCC, 89 non-PCC). HIPEC was performed in 180 of 277 patients (65 per cent), including 124 of 188 with PCC (66 per cent). Median overall survival (OS) was 14.7 (95 per cent c.i. 12.7 to 17.3) months in the PCC group versus 21.2 (14.7 to 36.4) months in the non-PCC group (P < 0.001). In multivariable analyses, PCC (hazard ratio (HR) 1.51, 95 per cent c.i. 1.01 to 2.25; P = 0.044) was associated with poorer OS, as were pN3, Peritoneal Cancer Index (PCI), and resection with a completeness of cytoreduction score of 1, whereas HIPEC was associated with improved OS (HR 0.52; P < 0.001). The benefit of CRS-HIPEC over CRS alone was consistent, irrespective of histology, with a median OS of 16.7 versus 11.3 months (HR 0.60, 0.39 to 0.92; P = 0.018) in the PCC group, and 34.5 versus 14.3 months (HR 0.43, 0.25 to 0.75; P = 0.003) in the non-PCC group. Non-PCC and HIPEC were independently associated with improved recurrence-free survival and fewer peritoneal recurrences. In patients who underwent HIPEC, PCI values of below 7 and less than 13 were predictive of OS in PCC and non-PCC populations respectively. CONCLUSION In selected patients, CRS-HIPEC offers acceptable outcomes among those with gastric PCC and long survival for patients without PCC.
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Affiliation(s)
- P E Bonnot
- Department of Surgical Oncology, Centre Georges Francois Leclerc, Dijon, France.,Department of Surgical Oncology, CHU Lyon Sud, Hospices Civils de Lyon, Lyon, France
| | - A Lintis
- Department of Surgical Oncology, CHU Lyon Sud, Hospices Civils de Lyon, Lyon, France.,Department of General Surgery, CHU Lille, Lille, France
| | - F Mercier
- Department of Surgical Oncology, CHU Lyon Sud, Hospices Civils de Lyon, Lyon, France.,Department of Surgical Oncology, Centre Hospitalier Universitaire de Montreal, Montreal, Quebec, Canada
| | - N Benzerdjeb
- Pathology Department, CHU Lyon Sud, Hospices Civils de Lyon, University of Lyon, Lyon, France
| | - G Passot
- Department of Surgical Oncology, CHU Lyon Sud, Hospices Civils de Lyon, Lyon, France
| | - M Pocard
- Department of Surgical Oncology, Hôpital Lariboisière, Paris, France
| | - B Meunier
- Department of Surgical Oncology, CHU Pontchaillou, Rennes, France
| | - J M Bereder
- Department of Surgical Oncology, CHU L'Archet, Nice, France
| | - K Abboud
- Department of Surgical Oncology, CHU St Etienne, St Etienne, France
| | - F Marchal
- Department of Surgical Oncology, Institut de Cancérologie de Lorraine, Université de Lorraine, Nancy, France
| | - F Quenet
- Department of Surgical Oncology, Centre Val D'Aurelle, Montpellier, France
| | - D Goere
- Department of Surgical Oncology, Institut Gustave Roussy, Villejuif, France
| | - S Msika
- Department of Surgical Oncology, CHU Louis Mourier, Paris, France
| | - C Arvieux
- Department of Surgical Oncology, CHU La Tronche, Grenoble, France
| | - N Pirro
- Department of Surgical Oncology, CHU La Timone, Marseille, France
| | - R Wernert
- Department of Surgical Oncology, Institut Paul Papin, Angers, France
| | - P Rat
- Department of Surgical Oncology, CHU Le Bocage, Dijon, France
| | - J Gagnière
- Department of Surgical Oncology, CHU Clermont-Ferrand, Clermont Ferrand, France
| | - J H Lefevre
- Department of Surgical Oncology, Hôpital Saint-Antoine, AP-HP, Paris, Sorbonne Université, Paris, France
| | - T Courvoisier
- Department of Surgical Oncology, CHU Poitiers, Poitiers, France
| | - R Kianmanesh
- Department of Surgical Oncology, CHU Reims, Reims, France
| | - D Vaudoyer
- Department of Surgical Oncology, CHU Lyon Sud, Hospices Civils de Lyon, Lyon, France
| | - M Rivoire
- Department of Surgical Oncology, Centre Léon Bérard, Lyon, France
| | - P Meeus
- Department of Surgical Oncology, Centre Léon Bérard, Lyon, France
| | - L Villeneuve
- Department of Surgical Oncology, CHU Lyon Sud, Hospices Civils de Lyon, Lyon, France.,Unité de Recherche Clinique, Pôle Information Médicale Evaluation Recherche, Hospices Civils de Lyon, Lyon, France
| | - G Piessen
- Department of General Surgery, CHU Lille, Lille, France
| | - O Glehen
- Department of Surgical Oncology, CHU Lyon Sud, Hospices Civils de Lyon, Lyon, France
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Levenson G, Voron T, Paye F, Balladur P, Debove C, Chafai N, De Dios AG, Lefevre JH, Parc Y. Tumor downstaging after neoadjuvant chemotherapy determines survival after surgery for gastric adenocarcinoma. Surgery 2021; 170:1711-1717. [PMID: 34561115 DOI: 10.1016/j.surg.2021.08.021] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2020] [Revised: 07/20/2021] [Accepted: 08/15/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND Since 2006, surgery combined with perioperative chemotherapy is the standard of care for resectable gastric adenocarcinoma in Europe. Specific effects of neoadjuvant chemotherapy remain unknown. The aim was to evaluate the rate of tumor downstaging and its impact on survival in patients undergoing curative resection after neoadjuvant chemotherapy (NeoCT) for gastric adenocarcinoma. MATERIAL AND METHODS All patients treated in a curative intent for gastric or esophagogastric junction adenocarcinomas between 1996 and 2016 in our high-volume center were retrospectively included. Tumor downstaging after NeoCT was defined as ypTN inferior to cTN. The accuracy of clinical staging was evaluated in patients treated by upfront surgery before 2006. RESULTS During the study period, 491 patients were operated for gastric adenocarcinoma, and 449 patients were finally analyzed. Among the 163 (36.3%) patients who received NeoCT, 61 (37.4%) had tumor downstaging. Overall survival and disease-free survival were longer in patients with tumor downstaging compared to patients without it (5-year survival: 84.8% vs 49.7%; P = .002 and 61.7% vs 43.4%; P = .054). In multivariate analysis tumor downstaging was an independent prognosis factor for better overall survival (HR = 5.258; P = .002) and disease-free survival (HR = 2.286; P = .028). Moreover, 45.5% of patients staged cT1-T2N0, in whom upfront surgery was performed, were understaged and ultimately had a more advanced tumor on pathological analysis. CONCLUSION Response to neoadjuvant chemotherapy constitutes a major prognostic factor for overall and disease-free survival. In the absence of predictive factors for tumor downstaging, the indication for perioperative chemotherapy should remain broad, in particular because of the low accuracy of pretherapeutic staging and therefore the high risk of understaging tumors.
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Affiliation(s)
- Guillaume Levenson
- Department of General and Digestive Surgery, Saint-Antoine Hospital, AP-HP, Paris, France
| | - Thibault Voron
- Department of General and Digestive Surgery, Saint-Antoine Hospital, AP-HP, Paris, France; Sorbonne Université, France.
| | - François Paye
- Department of General and Digestive Surgery, Saint-Antoine Hospital, AP-HP, Paris, France; Sorbonne Université, France
| | - Pierre Balladur
- Department of General and Digestive Surgery, Saint-Antoine Hospital, AP-HP, Paris, France; Sorbonne Université, France
| | - Clotilde Debove
- Department of General and Digestive Surgery, Saint-Antoine Hospital, AP-HP, Paris, France; Sorbonne Université, France
| | - Najim Chafai
- Department of General and Digestive Surgery, Saint-Antoine Hospital, AP-HP, Paris, France; Sorbonne Université, France
| | - Alba Gallego De Dios
- Department of General and Digestive Surgery, Saint-Antoine Hospital, AP-HP, Paris, France
| | - Jeremie H Lefevre
- Department of General and Digestive Surgery, Saint-Antoine Hospital, AP-HP, Paris, France; Sorbonne Université, France
| | - Yann Parc
- Department of General and Digestive Surgery, Saint-Antoine Hospital, AP-HP, Paris, France; Sorbonne Université, France
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29
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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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30
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Dong X, Sun G, Qu H, He Q, Hao Z. Prognostic Significance of Signet-Ring Cell Components in Patients With Gastric Carcinoma of Different Stages. Front Surg 2021; 8:642468. [PMID: 34336913 PMCID: PMC8319562 DOI: 10.3389/fsurg.2021.642468] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Accepted: 05/14/2021] [Indexed: 01/14/2023] Open
Abstract
Background: Gastric carcinoma (GC), which contains signet ring cell (SRC) components are frequently observed in postoperative pathological assessment. This study aims to study the prognostic significance of SRC components in GC patients. Methods: From 2003 to 2017, surgically resected primary GC patients were retrospectively reviewed. All enrolled patients were divided into three groups according to the proportion of SRC. The overall survival (OS) and disease-free survival (DFS) of GC patients with different tumor stages were analyzed. Results: Patients with SRC or mixed-SRC were more associated with female, younger age, middle or lower third of the stomach, larger tumor, higher pN stage, and more lymphovascular invasion. For GC patients in stage I, multivariate survival analysis showed that age >60, SRC components >50%, and pT stage were independent prognostic factors for OS (all p < 0.05). The 5-year OS of patients with SRC were higher than that of patients with pure adenocarcinoma (p = 0.021). For GC patients in stage II/III, multivariate survival analysis showed that age >60, SRC proportion, surgical types, Borrmann's type, pT stage, pN stage, and lymphovascular invasion were independent prognostic factors for OS (all p < 0.05). The 5-year OS/DFS of patients with SRC were lower than that of patients with pure adenocarcinoma (p < 0.001). Conclusions: SRC seemed to be a favorable prognostic factor in GC patients in stage I. However, for GC patients in stage II/III, the SRC components were associated with poor prognosis, independent of other clinicopathological factors.
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Affiliation(s)
- Xiaoyuan Dong
- Department of Hematology, Qilu Hospital of Shandong University, Jinan, China
| | - Guorui Sun
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan, China
| | - Hui Qu
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan, China
| | - Qingsi He
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan, China
| | - Zhaofan Hao
- Department of Nephrology, Eastern District, Qilu Hospital of Shandong University, Jinan, China
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31
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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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32
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Díaz Del Arco C, Ortega Medina L, Estrada Muñoz L, García Gómez de Las Heras S, Fernández Aceñero MJ. Is there still a place for conventional histopathology in the age of molecular medicine? Laurén classification, inflammatory infiltration and other current topics in gastric cancer diagnosis and prognosis. Histol Histopathol 2021; 36:587-613. [PMID: 33565601 DOI: 10.14670/hh-18-309] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Gastric cancer (GC) is the fifth most common cancer and the third cause of cancer-related deaths worldwide. In western countries, more than half of GC patients are diagnosed at advanced stages and 5-year survival rates range between 20-30%. The only curative treatment is surgery, and despite recent advances in oncological therapies, GC prognosis is still poor. The main prognostic tool for patient categorization and treatment selection is the TNM classification, but its limitations are being increasingly recognized. Early recurrences may occur in early-stage disease, and patients at the same stage show heterogeneous outcomes. Thus, there is a need to improve GC stratification and to identify new prognostic factors, which may allow us to select drug-susceptible populations, refine patient grouping for clinical trials and discover new therapeutic targets. Molecular classifications have been developed, but they have not been translated to the clinical practice. On the other hand, histological assessment is cheap and widely available, and it is still a mainstay in the era of molecular medicine. Furthermore, histological features are acquiring new roles as reflectors of the genotype-phenotype correlation, and their potential impact on patient management is currently being analyzed. The aim of this literature review is to provide a modern overview of the histological assessment of GC. In this study, we discuss recent topics on the histological diagnosis of GC, focusing on the current role of Laurén classification and the potential value of new histological features in GC, such as inflammatory infiltration and tumor budding.
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Affiliation(s)
- Cristina Díaz Del Arco
- Department of Surgical Pathology, Hospital Clínico San Carlos, Madrid, Spain.
- Complutense University of Madrid, Madrid, Spain
| | - Luis Ortega Medina
- Complutense University of Madrid, Madrid, Spain
- Department of Surgical Pathology, Hospital Clínico San Carlos, Madrid, Spain
| | | | | | - Mª Jesús Fernández Aceñero
- Complutense University of Madrid, Madrid, Spain
- Department of Surgical Pathology, Hospital General Universitario Gregorio Marañón, Madrid, Spain
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Zhang C, Liu R, Zhang WH, Chen XZ, Liu K, Yang K, Chen XL, Zhao LY, Chen ZX, Zhou ZG, Hu JK. Difference Between Signet Ring Cell Gastric Cancers and Non-Signet Ring Cell Gastric Cancers: A Systematic Review and Meta-Analysis. Front Oncol 2021; 11:618477. [PMID: 34026606 PMCID: PMC8139399 DOI: 10.3389/fonc.2021.618477] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2020] [Accepted: 02/22/2021] [Indexed: 02/05/2023] Open
Abstract
Background: There is controversy about the characteristics and prognostic implications of signet ring cell gastric cancers and non-signet ring cell gastric cancers. Objective: This study aims to evaluate clinicopathological characteristics and prognoses of signet ring cell carcinoma (SRCC) and non-signet ring cell carcinoma (NSRCC) of stomach. Methods: Studies compared between SRCC and NSRCC of the stomach after gastrectomy and published before September 1st, 2020, in the PubMed, Cochrane, and Embase databases, were identified systematically. Results: A total of 2,865 studies were screened, and 36 studies were included, with 19,174 patients in the SRCC group and 55,942 patients in the NSRCC group. SRCC patients were younger in age (P < 0.001), less likely to be male patients (P < 0.001), more afflicted with upper third lesions (P < 0.001), and presenting with more Borrmann type IV tumors (P = 0.005) than NSRCC patients. Lymph nodes metastasis was similar between SRCC and NSRCC patients with advanced tumor stage (OR: 0.86, 95% CI: 0.671.10, P = 0.23), but lower in the SRCC than NSRCC patients with early tumor stage (OR: 0.73; 95% CI: 0.560.98, P = 0.02). SRCC patients had comparable survival outcomes with NSRCC patients for early gastric cancers (HR: 1.05, 95% CI: 0.651.68, P < 0.001) but had significantly poor prognosis for patients with advanced tumor stage (HR: 1.50, 95% CI: 1.281.76, P < 0.001). Conclusions: Signet ring cell carcinomas of the stomach are an increasingly common histopathological subtype of gastric cancers. These kinds of patients tend to be younger in age and more often female. Although, signet ring cell gastric cancer is a negative prognostic factor for patients with advanced stage. The difference is that for early stage of signet ring cell gastric cancers, it has low lymph nodes metastasis rate and comparable prognosis with non-signet ring cell cancers.
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Affiliation(s)
- Chi Zhang
- Department of Gastrointestinal Surgery, Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Ran Liu
- Engineering Research Center of Medical Information Technology, Ministry of Education, West China Hospital, Sichuan University, Chengdu, China
| | - Wei-Han Zhang
- Department of Gastrointestinal Surgery, Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Xin-Zu Chen
- Department of Gastrointestinal Surgery, Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Kai Liu
- Department of Gastrointestinal Surgery, Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Kun Yang
- Department of Gastrointestinal Surgery, Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Xiao-Long Chen
- Department of Gastrointestinal Surgery, Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Lin-Yong Zhao
- Department of Gastrointestinal Surgery, Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Zhi-Xin Chen
- Department of Gastrointestinal Surgery, Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Zong-Guang Zhou
- Department of Gastrointestinal Surgery, Laboratory of Digestive Surgery, State Key Laboratory of Biotherapy, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Jian-Kun Hu
- Department of Gastrointestinal Surgery, Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China
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Kano Y, Ohashi M, Muneoka Y, Takahari D, Chin K, Yamaguchi K, Ida S, Kumagai K, Makuuchi R, Sano T, Nunobe S. Different risk factors for three major recurrence patterns of pathological stage II or III gastric cancer patients who completed adjuvant S-1 monotherapy. Eur J Surg Oncol 2021; 47:3097-3104. [PMID: 33931261 DOI: 10.1016/j.ejso.2021.04.018] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2020] [Revised: 03/22/2021] [Accepted: 04/15/2021] [Indexed: 02/07/2023] Open
Abstract
INTRODUCTION After curative gastrectomy followed by 1-year adjuvant S-1 monotherapy for pathological stage (pStage) II or III gastric cancer, some patients experience peritoneal, hematogenous, or lymph nodal recurrence. However, risk factors for each recurrence pattern despite completed adjuvant S-1 monotherapy remain unclear. The aim of this study was to determine which factors influence each recurrence type after curative gastrectomy followed by 1-year adjuvant S-1 monotherapy. MATERIALS AND METHODS A total of 380 patients with pStage II or III gastric cancer who completed 1-year adjuvant S-1 monotherapy after R0 gastrectomy between January 2008 and December 2013 were enrolled in this study. The risk factors that were associated with peritoneal, hematogenous, and lymph nodal recurrence were investigated by univariate and multivariate analyses. RESULTS Eighty (21.1%) of 380 patients developed recurrence. As the first site, peritoneal, hematogenous, and lymph nodal recurrence occurred in 42 (11.1%), 26 (6.8%), and 12 (3.2%) patients, respectively. In multivariate analysis, peritoneal metastasis was associated with signet ring cell carcinoma (P < 0.001), pT4 (P = 0.001), and pN3 (P < 0.001), while hematogenous recurrence was associated with pN3 (P = 0.019) and later initiation of S-1 (P = 0.013), and lymph nodal recurrence was associated with pN3 (P = 0.002). CONCLUSION The risk factors for peritoneal, hematogenous, and lymph nodal recurrence in pStage II or III gastric cancer patients who complete adjuvant S-1 monotherapy differ. This information may be helpful for daily surveillance of recurrence in post-operative and chemotherapeutic patients. Furthermore, it may be a useful reference to develop novel perioperative chemotherapy.
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Affiliation(s)
- Yosuke Kano
- Department of Gastroenterological Surgery, Gastroenterological Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan; Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Manabu Ohashi
- Department of Gastroenterological Surgery, Gastroenterological Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
| | - Yusuke Muneoka
- Department of Gastroenterological Surgery, Gastroenterological Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan; Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Daisuke Takahari
- Department of Gastroenterological Medicine, Gastroenterological Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Keisho Chin
- Department of Gastroenterological Medicine, Gastroenterological Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Kensei Yamaguchi
- Department of Gastroenterological Medicine, Gastroenterological Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Satoshi Ida
- Department of Gastroenterological Surgery, Gastroenterological Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Koshi Kumagai
- Department of Gastroenterological Surgery, Gastroenterological Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Rie Makuuchi
- Department of Gastroenterological Surgery, Gastroenterological Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Takeshi Sano
- Department of Gastroenterological Surgery, Gastroenterological Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Souya Nunobe
- Department of Gastroenterological Surgery, Gastroenterological Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
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Prognostic Nomograms for Nonelderly Adults with Gastric Signet Ring Cell Carcinoma. BIOMED RESEARCH INTERNATIONAL 2021; 2021:1274527. [PMID: 33834061 PMCID: PMC8016563 DOI: 10.1155/2021/1274527] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/17/2020] [Revised: 01/21/2021] [Accepted: 02/28/2021] [Indexed: 01/19/2023]
Abstract
Background Nomograms were established to predict the survival for gastric signet ring cell carcinoma (GSRC) in young and middle-aged adults. Material and Methods. Eligible patients with GSRC from 2004 to 2015 were collected from the Surveillance, Epidemiology, and End Results (SEER) database and then divided into a training and a testing cohort in proportion. Independent prognostic factors were picked by univariate and multivariate Cox regression analysis to set up nomograms. The predictive effect and clinical value of nomograms were evaluated by the concordance index (C-index), calibration curves, and receiver operating characteristic curve (ROC). Results A total of 1686 GSRC patients were subsumed into this case for analysis, including a training (n = 1180) and a testing cohort (n = 506). Independent risk factors related to overall survival (OS) and cancer-specific survival (CSS) comprised of race, TNM stage, tumor size, number of positive lymph nodes (PLNE), and chemotherapy. For OS, the C-indexes of the training and testing cohorts were 0.737 and 0.752, while for CSS, C-indexes were, respectively, 0.749 and 0.751. These revealed that nomograms accurately predicted OS and CSS. Calibration curves and ROC demonstrated the apparent superiority of nomograms. Conclusion We built a well-understood and comprehensive prognostic assessment model for GSRC, which provided an individualized survival prediction in the form of a quantitative score that can be considered for clinical practice.
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Morgant S, Artru P, Oudjit A, Lourenco N, Pasquer A, Walter T, Gornet JM, Rouquette A, Brezault C, Coriat R. Endoscopic ultrasound efficacy in staging gastric linitis plastica lesion: a retrospective multicentric French study. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:50. [PMID: 33553343 PMCID: PMC7859799 DOI: 10.21037/atm-20-3474] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Accepted: 09/25/2020] [Indexed: 12/29/2022]
Abstract
BACKGROUND Endoscopic ultrasound (EUS) is a key imaging technique in gastric cancer (GC). The aim of this study was to evaluate the performance of EUS in the staging of parietal and lymph node involvement in linitis plastica (LP) compared to "classical" GC. METHODS A retrospective multicentric French study was conducted on patients with no metastatic LP and operated by gastrectomy. A 2/1 matching based on pTNM stage and center was performed with GC. RESULTS Forty-three patients were included, sixteen patients in the LP group and 27 in the control group. Sensitivity and specificity of EUS for diagnosis of T3-T4 parietal invasion were 77% and 100% respectively in the LP group and 89% and 56% respectively in the control group. Sensitivity and specificity of EUS for diagnosis of lymph node involvement were 73% and 80%, respectively in the LP group and 88% and 50%, respectively in the control group. Patients from LP group had significantly more advanced histological lesion, and frequent undiagnosed peritoneal carcinomatosis. CONCLUSIONS This study evaluated for the first time in a European population, the preoperative EUS performance in LP. Our study identified a similar sensitivity and specificity of the EUS in LP compared to "classical" GC paving for a broader use of EUS in preoperative settings.
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Affiliation(s)
- Stephanie Morgant
- Gastroenterology and digestive oncology unit, Hôpital Cochin, Paris, France
| | - Pascal Artru
- Gastroenterology and Digestive Unit, Jean Mermoz Clinic, Lyon, France
| | - Ammar Oudjit
- Radiology Unit, Cochin Teaching Hospital, Paris, France
| | - Nelson Lourenco
- Gastroenterology Unit, Saint-Louis Teaching Hospital, Paris, France
| | - Arnaud Pasquer
- Digestive Surgery Unit, Edouard Herriot Teaching Hospital, Lyon, France
| | - Thomas Walter
- Oncology Unit, Edouard Herriot Teaching Hospital, Lyon, France
| | - Jean-Marc Gornet
- Gastroenterology Unit, Saint-Louis Teaching Hospital, Paris, France
| | | | - Catherine Brezault
- Gastroenterology and digestive oncology unit, Hôpital Cochin, Paris, France
| | - Romain Coriat
- Gastroenterology and digestive oncology unit, Hôpital Cochin, Paris, France
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Jeong SH, Park M, Park SY, Park J, Kim TH, Lee YJ, Jung EJ, Ju YT, Jeong CY, Kim JY, Ko GH, Kim M, Nam KT, Goldenring JR. Transcriptome Analysis and the Prognostic Role of NUDC in Diffuse and Intestinal Gastric Cancer. Technol Cancer Res Treat 2021; 20:15330338211019501. [PMID: 34060350 PMCID: PMC8173992 DOI: 10.1177/15330338211019501] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Revised: 03/05/2021] [Accepted: 04/19/2021] [Indexed: 12/24/2022] Open
Abstract
INTRODUCTION There have been few studies about gene differences between patients with diffuse-type gastric cancer and those with intestinal-type gastric cancer. The aim of this study was to compare the transcriptomes of signet ring cell gastric cancer (worst prognosis in diffuse-type) and well-differentiated gastric cancer (best prognosis in intestinal-type); NUDC was identified, and its prognostic role was studied. MATERIALS AND METHODS We performed next-generation sequencing with 5 well-differentiated gastric cancers and 3 of signet ring cell gastric cancer surgical samples. We performed gene enrichment and functional annotation analysis using the Database for Annotation, Visualization and Integrated Discovery bioinformatics resources. Immunohistochemistry was used to validate NUDC expression. RESULTS Overall, 900 genes showed significantly higher expression, 644 genes showed lower expression in signet ring cell gastric cancer than in well-differentiated gastric cancers, and there was a large difference in adhesion, vascular development, and cell-to-cell junction components between the 2 subtypes. We performed variant analysis and found 52 variants and 30 cancer driver genes, including NUDC. We analyzed NUDC expression in gastric cancer tissue and its relationship with prognosis. Cox proportional hazard analysis identified T stage, N stage, and NUDC expression as independent risk factors for survival (P < 0.05). The overall survival of the NUDC-positive group was significantly higher (53.2 ± 0.92 months) than that of the NUDC-negative group (44.6 ± 3.7 months) (P = 0.001) in Kaplan-Meier survival analysis. CONCLUSION We found 30 cancer driver gene candidates and found that the NUDC-positive group showed significantly better survival than the NUDC-negative group via variant analysis.
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Affiliation(s)
- Sang-Ho Jeong
- Department of Surgery, School of Medicine, Gyeongsang National University, Jinju, South Korea
- Department of Surgery, Gyeongsang National University, Changwon Hospital, Changwon, South Korea
| | - Miyeong Park
- Department of Anesthesiology, Gyeongsang National University, Changwon Hospital, Changwon, South Korea
| | - Sun Yi Park
- Department of Surgery, School of Medicine, Gyeongsang National University, Jinju, South Korea
| | - Jiho Park
- Department of Surgery, School of Medicine, Gyeongsang National University, Jinju, South Korea
| | - Tae-Han Kim
- Department of Surgery, Gyeongsang National University, Changwon Hospital, Changwon, South Korea
| | - Young-Joon Lee
- Department of Surgery, School of Medicine, Gyeongsang National University, Jinju, South Korea
| | - Eun-Jung Jung
- Department of Surgery, School of Medicine, Gyeongsang National University, Jinju, South Korea
- Department of Surgery, Gyeongsang National University, Changwon Hospital, Changwon, South Korea
| | - Young-tae Ju
- Department of Surgery, School of Medicine, Gyeongsang National University, Jinju, South Korea
| | - Chi-Young Jeong
- Department of Surgery, School of Medicine, Gyeongsang National University, Jinju, South Korea
| | - Ju-Yeon Kim
- Department of Surgery, School of Medicine, Gyeongsang National University, Jinju, South Korea
| | - Gyung Hyuck Ko
- Department of Pathology, School of Medicine, Gyeongsang National University, Jinju, South Korea
| | - Minhye Kim
- Department of Pathology, School of Medicine, Gyeongsang National University, Jinju, South Korea
| | - Ki Taek Nam
- Severance Biomedical Science, Yonsei University College of Medicine, Seodaemun-gu, South Korea
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Li Y, Zhu Z, Ma F, Xue L, Tian Y. Gastric Signet Ring Cell Carcinoma: Current Management and Future Challenges. Cancer Manag Res 2020; 12:7973-7981. [PMID: 32943931 PMCID: PMC7478370 DOI: 10.2147/cmar.s268032] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Accepted: 08/15/2020] [Indexed: 12/26/2022] Open
Abstract
Recent advances in the epidemiology, pathology, molecular mechanisms, and combined modality therapy (CMT) fields have shown that gastric signet ring cell carcinoma (GSRC) should be considered a distinct cancerous entity. Clinical management of this cancer is challenging, with chemoradioresistance and poor outcomes in advanced stages. Pathological and molecular sets of GSRC demonstrate different features of poor cohesion and differentiation according to the WHO, Japanese Gastric Cancer Association, and Laurén classifications. These features also result in poor response to adjuvant and neoadjuvant chemoradiotherapy. Certain studies of GSRC showed the disputed effectiveness of hyperthermic intraperitoneal chemotherapy and immunotherapy. Our aim was to discuss how an improved understanding of these therapeutic benefits may provide better treatment selection for patients, and therefore improve survival. The challenges in the new understanding of GSRC in routine practice and pathology, and the current limitations of treatment will also be discussed.
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Affiliation(s)
- Yang Li
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China
| | - Zhikai Zhu
- School of Public Health, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China
| | - Fuhai Ma
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China
| | - Liyan Xue
- Department of Pathology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China
| | - Yantao Tian
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China
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Li Y, Zhu Z, Ma F, Xue L, Tian Y. Improving survival of stage II-III primary gastric signet ring cell carcinoma by adjuvant chemoradiotherapy. Cancer Med 2020; 9:6617-6628. [PMID: 32744431 PMCID: PMC7520351 DOI: 10.1002/cam4.3342] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2020] [Revised: 05/10/2020] [Accepted: 07/11/2020] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND There is no consistent evidence about the appropriate treatment strategies for gastric signet ring cell carcinoma (GSRC) to improve prognosis. We conducted a population-based study to examine the effects of combined modality therapies on survival outcomes using the Surveillance, Epidemiology, and End Results (SEER) data. METHODS Analyses included stage II-III primary GSRC patients who were diagnosed between 2006 and 2016. Therapies were categorized as gastrectomy group, adjuvant chemotherapy (CT) group, neoadjuvant radiotherapy (RT) group, and adjuvant chemoradiotherapy (CRT) group. Survival analyses were conducted by Kaplan-Meier method and Cox proportional hazards models and subgrouped by gender, tumor site, stage at diagnosis, and number of lymph nodes removed. RESULTS Of the 1717 cases of stage II-III primary GSRC, the mean (SD) age was 59.6 (13.3) years, and over a half were male (52.8%). A total of 39.9% patients received adjuvant CRT and the 5-year overall survival (OS) rate was 34.6%. The median OS of patients treated with adjuvant CRT was significantly longer than that of the gastrectomy group (33 months vs 24 months, aHR = 0.71, 95% CI: 0.59, 0.84). Although the crude model showed a significant association between adjuvant CT and total survival (cHR = 0.81, 95% CI: 0.68, 0.96), the effect measure turned null in the multivariable and sub-group analysis. We did not find the significant effect of neoadjuvant RT. CONCLUSIONS In this study, GSRC patients with stage II-III experienced improved overall survival after receiving adjuvant CRT, which provides several treatment implications. More clinical trials will be needed to verify the conclusion derived from this study.
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Affiliation(s)
- Yang Li
- Department of Pancreatic and Gastric SurgeryNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences & Peking Union Medical CollegeBeijingChina
| | - Zhikai Zhu
- School of Public HealthChinese Academy of Medical Sciences & Peking Union Medical CollegeBeijingChina
- Department of OncologyGeorgetown University School of MedicineWashingtonDCUSA
| | - Fuhai Ma
- Department of Pancreatic and Gastric SurgeryNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences & Peking Union Medical CollegeBeijingChina
| | - Liyan Xue
- Department of PathologyNational Cancer Center/Cancer HospitalChinese Academy of Medical Sciences & Peking Union Medical CollegeBeijingChina
| | - Yantao Tian
- Department of Pancreatic and Gastric SurgeryNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences & Peking Union Medical CollegeBeijingChina
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Turgeon MK, Gamboa AC, Rupji M, Lee RM, Switchenko JM, El-Rayes BF, Russell MC, Cardona K, Kooby DA, Staley CA, Maithel SK, Shah MM. Should Signet Ring Cell Histology Alter the Treatment Approach for Clinical Stage I Gastric Cancer? Ann Surg Oncol 2020; 28:97-105. [PMID: 32524459 DOI: 10.1245/s10434-020-08714-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2020] [Indexed: 12/23/2022]
Abstract
BACKGROUND Surgery alone is standard-of-care for stage I gastric adenocarcinoma; however, clinicians can offer preoperative therapy for clinical stage I disease with signet ring cell histology, given its presumed aggressive biology. We aimed to assess the validity of this practice. METHODS The National Cancer Database (2004-2015) was reviewed for patients with clinical stage I signet ring cell gastric adenocarcinoma who underwent treatment with surgery alone, perioperative chemotherapy, neoadjuvant therapy, or adjuvant therapy. Analysis was stratified by preoperative clinical/pathologic stage. Primary outcome was overall survival (OS). RESULTS Of 1018 patients, median age was 60 years (±14); 53% received surgery alone (n = 542), 5% received perioperative chemotherapy (n = 47), 12% received neoadjuvant therapy (n = 125), and 30% received adjuvant therapy (n = 304). For clinical stage I disease, surgery alone was associated with an improved 5-year OS rate (71%) versus perioperative chemotherapy (58%), neoadjuvant therapy (38%), or adjuvant therapy (52%) [overall p < 0.01]. For pathologic stage I, surgery alone had equivalent or improved survival compared with perioperative, neoadjuvant, and adjuvant therapy (5-year OS: 78% vs. 89% [p = 0.77] vs. 64% [p = 0.04] vs. 84% [p = 0.99]). Adjuvant therapy was associated with improved 5-year OS compared with pretreatment for those patients upstaged (37%) to pathologic stage II/III (55% vs. 36% and 34% vs. 7%; all p < 0.01). CONCLUSIONS This stage-specific study demonstrates improved survival with surgery alone for clinical stage I signet ring cell gastric adenocarcinoma. Despite 37% of clinical stage I patients being upstaged to pathologic stage II/III, adjuvant therapy offers a favorable rescue strategy, with improved outcomes compared with those treated preoperatively. Surgery alone also affords similar or improved survival for pathologic stage I disease versus multimodality therapy. This study challenges the bias to overtreat stage I signet ring cell gastric adenocarcinoma.
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Affiliation(s)
- Michael K Turgeon
- Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA.,Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Adriana C Gamboa
- Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Manali Rupji
- Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Rachel M Lee
- Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Jeffrey M Switchenko
- Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA, USA
| | - Bassel F El-Rayes
- Department of Hematology and Medical Oncology, Emory University, Atlanta, GA, USA
| | - Maria C Russell
- Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Kenneth Cardona
- Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - David A Kooby
- Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Charles A Staley
- Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Shishir K Maithel
- Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Mihir M Shah
- Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA. .,Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, USA.
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Zhao B, Lv W, Zhang J, Zhang J, Huang B, Lin J. Different prognostic significance of signet ring cell histology for early and advanced gastric cancer patients: a systematic review and meta-analysis. Expert Rev Gastroenterol Hepatol 2020; 14:499-509. [PMID: 32421372 DOI: 10.1080/17474124.2020.1769476] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
OBJECTIVE To review relevant studies and perform a meta-analysis to evaluate the prognostic significance of signet ring cell (SRC) histology for gastric cancer (GC) patients. METHODS Systematic literature search was performed using PubMed and Embase databases. The relevant data were extracted and the association between SRC histology and survival outcome were evaluated using a fixed-effect or random-effect model. RESULTS A total of 21 studies were included in this meta-analysis. The prevalence of SRC histology varied from 8.7% to 50%. SRC histology type was associated with poorer OS (HR: 1.12, 95%CI: 1.01-1.23, P = 0.034; I2 = 85.1%) and DFS (HR: 1.17, 95%CI: 1.00-1.37, P = 0.040; I2 = 63.6%). The subgroup analysis indicated that SRC type had a better OS than non-SRC type for early GC patients (HR: 0.60, 95%CI: 0.48-0.75, P < 0.001; I2 = 33.7%). However, it was a poor prognostic factor for advanced GC when excluding stage IV patients (HR: 1.18, 95%CI: 1.07-1.29, P < 0.001; I2 = 6.5%). SRC type had a higher risk of peritoneal recurrence than non-SRC type (OR: 1.36, 95%CI: 1.06-1.75, P = 0.017; I2 = 1.3%). CONCLUSION SRC type had a distinctly different prognostic significance for early and advanced GC patients. SRC type was associated with better survival outcomes in early GC patients, but it was a predictive factor for poor survival in advanced GC patients.
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Affiliation(s)
- Bochao Zhao
- Department of Surgical Oncology, First Affiliated Hospital of China Medical University , Shenyang, P.R.China
| | - Wu Lv
- Department of General Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute , Shenyang, P.R.China
| | - Jingting Zhang
- Department of Surgical Oncology, First Affiliated Hospital of China Medical University , Shenyang, P.R.China
| | - Jiale Zhang
- Department of Surgical Oncology, First Affiliated Hospital of China Medical University , Shenyang, P.R.China
| | - Baojun Huang
- Department of Surgical Oncology, First Affiliated Hospital of China Medical University , Shenyang, P.R.China
| | - Jie Lin
- Department of General Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute , Shenyang, P.R.China
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Ramaswamy A, Bhargava P, Ostwal V. Real-World Long-Term Outcomes with Perioperative EOX in D2 Gastrectomy: a Meaningful Look While We Switch to FLOT-4. J Gastrointest Cancer 2020; 51:703-708. [PMID: 31956953 DOI: 10.1007/s12029-020-00358-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
INTRODUCTION Data regarding long-term survival and prognosis in loco-regionally advanced, non-metastatic gastric cancers (GC) using perioperative chemotherapy and D2 lymphadenectomies from India is scarce. MATERIALS AND METHODS The study is a retrospective evaluation of locally advanced gastric cancers who received epirubicin-oxaliplatin-capecitabine (EOX) as perioperative therapy from May 2013 to December 2015 at Tata Memorial Hospital, Mumbai. The report concentrates on long-term survival outcomes and prognostic factors. Event-free survival (EFS) and overall survival (OS) were calculated using Kaplan-Meier method. RESULTS Two hundred and sixty-eight patients were started on EOX regimen, of which 200 patients (74.6%) underwent definitive resection with D2 lymphadenectomy. With a median follow-up of 52.7 months, the estimated median 3-year and 5-year EFS were 38.5% and 36.3% respectively. The estimated median 3-year and 5-year OS were 41.7% and 37.6% respectively. Patients younger than age 40 years [HR 1.55 (1.034-2.321); p = 0.034] and with poorly differentiated histology [HR 0.65 (0.446-0.944); p = 0.024] had inferior OS compared to their counterparts. CONCLUSIONS Long-term OS in Indian patients in non-metastatic GC with EOX chemotherapy and D2 lymphadenectomy is similar to previously published Western data. Younger Indian patients fare worse than their older counterparts and this needs further evaluation.
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Affiliation(s)
- Anant Ramaswamy
- Department of Medical Oncology, TMH Homi Bhabha National Institute, E. Borges Road, Parel, Mumbai, 400012, India
| | - Prabhat Bhargava
- Department of Medical Oncology, TMH Homi Bhabha National Institute, E. Borges Road, Parel, Mumbai, 400012, India
| | - Vikas Ostwal
- Department of Medical Oncology, TMH Homi Bhabha National Institute, E. Borges Road, Parel, Mumbai, 400012, India.
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Jouini R, Khanchel F, Sabbah M, Helal I, Gharsallah A, Ferchichi M, Hadded D, Zaafouri H, Ben Brahim E, Ben Maamer A, Debbiche AC. Prognostic significance of poorly cohesive gastric carcinoma in Tunisian patients. Heliyon 2020; 6:e03460. [PMID: 32195384 PMCID: PMC7078324 DOI: 10.1016/j.heliyon.2020.e03460] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2019] [Revised: 10/07/2019] [Accepted: 02/18/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND While the incidence of gastric cancer has decreased worldwide in recent decades, the incidence of poorly cohesive carcinoma (PCC) is rising. The prognostic significance of gastric PCC remains a subject of debate. OBJECTIVE To analyze the prognosis of gastric PCC in a Tunisian cohort. METHODS A total of 122 gastric adenocarcinoma patients who underwent curative gastrectomy from 2001 to 2014 at Habib Thameur hospital in Tunis, Tunisia were included. The clinicopathological parameters and prognosis of PCC were analyzed in comparison with non PCC (NPCC). RESULTS Sixty one patients (50%) presented PCC. Patients were younger in PCC group (p = 0,001). There was no difference in sex distribution between the two groups. PCC was more likely to be stage T4 (55.7% vs 34.4%; p = 0.033), N3 (67.8% vs 30%; p < 0.001) and have a higher metastatic lymph node ratio (p < 0.001). Hepatic metastases were more frequent in NPCC group (p = 0.031) whereas peritoneal carcinomatosis was more common in PCC group (p = 0.004). Perineural invasion was more frequent in PCC group (p = 0.001). Resection margins were more often positive in PCC group (31.1% vs 9.8%; p = 0.004). There was no difference in recurrence rate between the 2 groups (p = 0.348). The 5-year survival was similar in the NPCC and PCC (respectively 43% vs 23 %; p = 0.247). Survival rates were also comparable in early stage (100% vs 80% respectively for PCC and NPCC; p = 0.527) as well as for advanced stage (16% vs 35% respectively for PCC and NPCC; p = 0.538). PCC was not a prognostic factor for survival. Interestingly, advanced age, adjacent structures invasion, positive resection margins were specific prognostic factors for PCC. CONCLUSION In our study PCC was not a prognostic factor for survival. Advanced age, adjacent structures invasion and positive resection margins were specific prognostic features for this histological subtype.
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Affiliation(s)
- Raja Jouini
- Department of Pathology, Habib Thameur Hospital, Tunis, Tunisia
- Faculty of Medicine of Tunis, Tunis El Manar University, Tunisia
| | - Fatma Khanchel
- Department of Pathology, Habib Thameur Hospital, Tunis, Tunisia
- Faculty of Medicine of Tunis, Tunis El Manar University, Tunisia
| | - Meriam Sabbah
- Department of Gastroenterology, Habib Thameur Hospital, Tunis, Tunisia
- Faculty of Medicine of Tunis, Tunis El Manar University, Tunisia
| | - Imen Helal
- Department of Pathology, Habib Thameur Hospital, Tunis, Tunisia
- Faculty of Medicine of Tunis, Tunis El Manar University, Tunisia
| | | | - Marwa Ferchichi
- Department of Pathology, Habib Thameur Hospital, Tunis, Tunisia
- Faculty of Sciences of Tunis, Tunis El Manar University, Tunisia
| | - Dhafer Hadded
- Faculty of Medicine of Tunis, Tunis El Manar University, Tunisia
- Department of Surgery, Habib Thameur Hospital, Tunisia
| | - Haithem Zaafouri
- Faculty of Medicine of Tunis, Tunis El Manar University, Tunisia
- Department of Surgery, Habib Thameur Hospital, Tunisia
| | - Ehsen Ben Brahim
- Department of Pathology, Habib Thameur Hospital, Tunis, Tunisia
- Faculty of Medicine of Tunis, Tunis El Manar University, Tunisia
| | - Anis Ben Maamer
- Faculty of Medicine of Tunis, Tunis El Manar University, Tunisia
- Department of Surgery, Habib Thameur Hospital, Tunisia
| | - Aschraf Chadli Debbiche
- Department of Pathology, Habib Thameur Hospital, Tunis, Tunisia
- Faculty of Medicine of Tunis, Tunis El Manar University, Tunisia
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Zhao ZT, Li Y, Yuan HY, Ma FH, Song YM, Tian YT. Identification of key genes and pathways in gastric signet ring cell carcinoma based on transcriptome analysis. World J Clin Cases 2020; 8:658-669. [PMID: 32149050 PMCID: PMC7052547 DOI: 10.12998/wjcc.v8.i4.658] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2020] [Revised: 01/20/2020] [Accepted: 02/15/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Gastric signet ring cell carcinoma (GSRCC) is one of the most malignant tumors. It has the features of high invasiveness, rapid progression, and resistance to chemotherapy. However, systematic analyses of mRNAs have not yet been performed for GSRCC. AIM To identify key mRNAs and signaling pathways in GSRCC. METHODS A transcriptome analysis of two GSRCC and two non-GSRCC samples was performed in this study. Differentially expressed mRNAs and pathways were identified based on the KEGG and PANTHER pathway annotations. The interactive relationships among the differential genes were mapped with the STRING database. Quantitative real-time polymerase chain reaction was used to validate the key gene expression in GSRCC. RESULTS About 1162 differential genes (using a 2-fold cutoff, P < 0.05) were identified in GSRCC compared with non-GSRCC. The enriched KEGG and PANTHER pathways for the differential genes included immune response pathways, metabolic pathways, and metastasis-associated pathways. Ten genes (MAGEA2, MAGEA2B, MAGEA3, MAGEA4, MAGEA6, MUC13, GUCA2A, FFAR4, REG1A, and REG1B) were identified as hub genes in the protein-protein interaction network. The expression levels of five genes (MAGEA2, MAGEA3, MAGEA4, MAGEA6, and REG1B) showed potential clinical value. CONCLUSION We have identified the potential key genes and pathways in GSRCC, and these hub genes and pathways could be diagnostic markers and therapeutic targets for GSRCC.
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Affiliation(s)
- Zi-Tong Zhao
- State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Yang Li
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Hong-Yu Yuan
- State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Fu-Hai Ma
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Yong-Mei Song
- State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Yan-Tao Tian
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
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Derieux S, Svrcek M, Manela S, Lagorce-Pages C, Berger A, André T, Taieb J, Paye F, Voron T. Evaluation of the prognostic impact of pathologic response to preoperative chemotherapy using Mandard's Tumor Regression Grade (TRG) in gastric adenocarcinoma. Dig Liver Dis 2020; 52:107-114. [PMID: 31427088 DOI: 10.1016/j.dld.2019.07.010] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2019] [Revised: 07/14/2019] [Accepted: 07/16/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND Perioperative chemotherapy is the gold standard in gastric cancer management. The prognostic significance of pathological response has been investigated in many malignancies, using Tumor Regression Grade (TRG). Its prognostic value in gastric cancer remains poorly known. AIMS This study aimed to assess the prognostic value of pathological response to chemotherapy, using Mandard's TRG in gastric cancer, and to identify factors predictive of response to chemotherapy. METHODS We retrospectively identified patients with gastric adenocarcinoma from two institutional surgical databases, with preoperative chemotherapy and subsequent gastrectomy. Pathological response was centrally reviewed using Mandard's TRG. RESULTS From 325 patients resected from a gastric cancer between 1997 and 2016, 109 underwent a preoperative chemotherapy. 42% were pathologic responders (TRG1-3) and 58% non-responders (TRG4-5). Five-years overall survival (OS) was 35% for non-responders, and 73% for responders (p = 0,006). Five-years disease-free survival (DFS) was 34% for non-responders and 65% for responders (p = 0,013). In multivariate analysis, pathological response was an independent prognostic factor of poor OS: HR = 2.736 (CI95% = 1.335-5.608; p = 0.006) and DFS: HR = 2.241 (CI95% = 1.130-4.446; p = 0.021). CONCLUSION TRG after preoperative chemotherapy is an important prognostic factor in patients resected for a gastric adenocarcinoma. Further studies should be performed to evaluate if adjuvant therapy should be adapted to pathological response.
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Affiliation(s)
- Simon Derieux
- Sorbonne University, Digestive surgery department, AP-HP, St Antoine Hospital, Paris, France.
| | - Magali Svrcek
- Sorbonne University, Department of pathology, AP-HP, St Antoine Hospital, Paris, France
| | - Sarah Manela
- Department of pathology, AP-HP, Georges Pompidou European Hospital, Paris, France
| | | | - Anne Berger
- Digestive surgery department, AP-HP, Georges Pompidou European Hospital, Paris, France
| | - Thierry André
- Sorbonne University, Medical oncology department, AP-HP, Saint Antoine Hospital, Paris, France
| | - Julien Taieb
- Digestive oncology department, AP-HP, Georges Pompidou European Hospital, Paris, France
| | - François Paye
- Sorbonne University, Digestive surgery department, AP-HP, St Antoine Hospital, Paris, France
| | - Thibault Voron
- Sorbonne University, Digestive surgery department, AP-HP, St Antoine Hospital, Paris, France
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Shi T, Song X, Liu Q, Yang Y, Yu L, Liu B, Wei J. Survival benefit of palliative gastrectomy followed by chemotherapy in stage IV gastric signet ring cell carcinoma patients: A large population-based study. Cancer Med 2019; 8:6010-6020. [PMID: 31448584 PMCID: PMC6792481 DOI: 10.1002/cam4.2521] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2019] [Revised: 08/04/2019] [Accepted: 08/14/2019] [Indexed: 12/18/2022] Open
Abstract
Background Stage IV gastric signet ring cell carcinoma (SRCC) is a type of malignant gastric cancer (GC) with poorer survival compared to metastatic non‐SRCC gastric cancer (NOS). However, chemotherapy alone was unable to maintain long‐term survival. This study aimed to evaluate survival benefit of palliative gastrectomy plus chemotherapy (PG+C) for metastatic gastric SRCC. Methods We obtained data on gastric cancer patients between 2010 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database. Statistical methods included χ2 tests, Kaplan‐Meier curves, COX models, propensity score matching (PSM) and subgroup analysis. Results Among 27 240 gastric cancer patients included, 4638 (17.03%) were SRCC patients. The proportion of patients with younger age, female gender, poorly differentiated grade and M1 stage was higher in SRCC than in NOS (P < .001). Multivariate analysis revealed that multiple metastatic sites (HR = 1.39, 95% CI: 1.14‐1.69, P = .001) was associated with increased mortality risk in metastatic SRCC. Median survival time was improved in metastatic SRCC receiving PG+C compared to PG/C alone (13 vs 7 months, P < .001). Notably, in subgroup analysis, 13 of 17 groups of metastatic SRCC patients with PG+C had prolonged overall survival compared to chemotherapy alone, especially for those with only one metastatic site (HR = 0.61, 95% CI: 0.51‐0.73, P < .001). Conclusions Our results suggested that there exists at least a selective group of stage IV gastric SRCC patients, who could benefit from palliative gastrectomy followed by chemotherapy compared to chemotherapy alone. Further prospective trials are needed to support our conclusion.
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Affiliation(s)
- Tao Shi
- The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, China
| | - Xueru Song
- The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, China
| | - Qin Liu
- The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, China
| | - Yang Yang
- The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, China
| | - Lixia Yu
- The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, China
| | - Baorui Liu
- The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, China
| | - Jia Wei
- The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, China
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The Impact of Epidemiological Factors and Treatment Interventions on Survival in Patients With Signet Ring Cell Carcinoma of the Pancreas. Am J Clin Oncol 2019; 41:1176-1184. [PMID: 29672365 DOI: 10.1097/coc.0000000000000447] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
OBJECTIVES Primary pancreatic signet ring cell carcinoma (SRCC) is a rare histologic variant of pancreatic carcinoma. A population-based analysis of pancreatic SRCC was performed to determine the predictive effects of epidemiological factors and treatment interventions on overall survival (OS) and disease-specific survival (DSS). MATERIALS AND METHODS The Surveillance, Epidemiology, and End Results registry was searched for pancreatic SRCC cases diagnosed between January 1, 1973 and December 31, 2013. Statistical analysis was performed using the Fisher exact test, χ(2) analysis, Kaplan-Meier method, log-rank test, and Cox proportional hazards regression. RESULTS The mean age among 497 patients was 66.6 years (SD, 11.9). Most patients were white (82.7%) and male (54.5%). The 1-, 2-, and 5-year OS rates were 17%, 9%, and 4%, respectively, while the corresponding 1-, 2-, and 5-year rates for DSS were 18%, 10%, and 5%, respectively. On univariable analysis; age, site, grade, stage, and treatment were predictive of OS and DSS (P<0.05). On multivariable analysis; radiation improved OS and DSS (adjusted hazard ratio [aHR], 0.592 and 0.589, respectively), pancreatectomy improved OS and DSS (aHR, 0.360 and 0.355, respectively), and combination therapy improved OS and DSS (aHR, 0.295 and 0.286, respectively). Age, site, and stage were also independent predictors of OS and DSS. Subgroup analysis demonstrated treatment to be an independent predictor of OS and DSS in localized/regional disease, in distant disease, and in patients diagnosed between 2000 and 2013. CONCLUSIONS Age, site, stage, and treatment independently predict OS and DSS in pancreatic SRCC.
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Harris C, Ostwal V, Vallathol DH, Dusane R, Mandavkar S, Patkar S, Ramaswamy A, Shrikhande SV. Calculation of a clinical predictive factors identifying peritoneal disease on a staging laparoscopy in gastric cancers. South Asian J Cancer 2019; 8:166-167. [PMID: 31489289 PMCID: PMC6699230 DOI: 10.4103/sajc.sajc_182_18] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/04/2022] Open
Abstract
INTRODUCTION Staging laparoscopy (SL) is the current standard staging workup for loco-advanced gastric cancers (GCs). Materials and Methods: We analyzed the data of all patients with loco-regionally advanced, nonmetastatic GCs, who underwent SL for the evaluation of peritoneal carcinomatosis (PC). MATERIALS AND METHODS We analyzed the data of all patients with loco-regionally advanced, nonmetastatic GCs, who underwent SL for the evaluation of peritoneal carcinomatosis (PC). RESULTS Between December 2013 and October 2016, 363 patients underwent SL, of which 75 (20.7%) were found to have PC on SL. Age ≤40 years, CA 19-9 > upper limit of normal, and low serum albumin levels (≤3.5 g/dl) correlated significantly with the presence of PC on SL. There was a statistically significant difference in the median overall survival between patients with radiologically detected PC and SL detected PC (8.67 months vs. 15.3 months;P < 0.0001). CONCLUSION SL upstaged disease status in 20.7% of patients. Clinical factors, identified in this study, need further validation in larger prospective cohorts before being used in clinical practice. Patients with radiologically detected PC have lower survival as compared to those with PC on SL.
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Affiliation(s)
- Caleb Harris
- Department of Surgical Oncology, North Eastern Indira Gandhi Regional Institutes of Health and Medical Sciences, Shillong, Meghalaya, India
| | - Vikas Ostwal
- Department of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India
| | | | - Rohit Dusane
- Department of Clinical Research Secretariat, Tata Memorial Hospital, Mumbai, Maharashtra, India
| | - Sarika Mandavkar
- Department of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India
| | - Shraddha Patkar
- Department of Clinical Surgical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India
| | - Anant Ramaswamy
- Department of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India
| | - Shailesh V. Shrikhande
- Department of Clinical Surgical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India
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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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Ren J, Niu G, Wang X, Song T, Hu Z, Ke C. Effect of Age on Prognosis of Gastric Signet-Ring Cell Carcinoma: A SEER Database Analysis. Med Sci Monit 2018; 24:8524-8532. [PMID: 30473583 PMCID: PMC6278247 DOI: 10.12659/msm.911766] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Background Age is a prognostic factor for multiple malignancies. In this study, we aimed to assess the effect of age on the cancer-specific survival (CSS) of patients with gastric signet-ring cell carcinoma (SRC). Material/Methods Information on patients with gastric SRC was extracted from the Surveillance, Epidemiology, and End Results database. Chi-squared tests were used to demonstrate distribution differences, and Kaplan-Meier analysis and Cox regression models were used to analyze the impact of age on CSS. Results A total of 4596 patients were enrolled and divided into 3 subgroups according to age (<45, 45–74, and >74 years old). Higher percentages of T4, N2, and M1 disease were observed in the <45-year-old group (all P<0.001). Kaplan-Meier plots showed that the youngest group had the most favorable 5-year CSS rate (36.3%), which remained true after stratification according to tumor stage. Multivariate Cox regression models demonstrated a poorer survival outcome for >74-year-old than for <45-year-old patients (hazard ratio 1.841, 95% confidence interval 1.636–2.071; P<0.001). Conclusions Young age is associated with improved survival, even though younger patients generally present with a more advanced-stage disease.
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Affiliation(s)
- Jun Ren
- Department of General Surgery, Shanghai Fifth People's Hospital, Fudan University, Shanghai, China (mainland)
| | - Gengming Niu
- Department of General Surgery, Shanghai Fifth People's Hospital, Fudan University, Shanghai, China (mainland)
| | - Xin Wang
- Department of General Surgery, Shanghai Fifth People's Hospital, Fudan University, Shanghai, China (mainland)
| | - Tao Song
- Department of General Surgery, Shanghai Fifth People's Hospital, Fudan University, Shanghai, China (mainland)
| | - Zhiqing Hu
- Department of General Surgery, Shanghai Fifth People's Hospital, Fudan University, Shanghai, China (mainland)
| | - Chongwei Ke
- Department of General Surgery, Shanghai Fifth People's Hospital, Fudan University, Shanghai, China (mainland)
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